Compounds > carboplatin
Page last updated: 2024-11-08

carboplatin

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth

Cross-References

ID SourceID
PubMed CID426756
SCHEMBL ID4964
MeSH IDM0024707

Synonyms (30)

Synonym
HMS3269H03
carboplatin ,
LOPAC0_000230
41575-94-4
nsc241240
1,1-cyclobutanedicarboxylate diammine platinum(ii)
platinum(ii),1-cyclobutanedicarboxylato)diammine-, cis-
platinum,1-cyclobutanedicarboxylato(2-)-o,o')-, (sp-4-2)-
paraplatin (bristol meyers)
platinum,1-cyclobutanedicarboxylato(2-)-o,o']-, (sp-4-2)-
NCGC00167800-01
cas-41575-94-4
pharmakon1600-01502106
nsc758182
nsc-758182
EPITOPE ID:194801
1,1-cyclobutanedicarboxylatodiammineplatinum(ii)
SCHEMBL4964
NCGC00263858-02
tox21_112586_1
AB01273939-01
platinum, diammine[1,1-cyclobutanedicarboxylato(2-)-.kappa.o,.kappa.o'']-, (sp-4-2)-
mfcd00070464
diamino[cyclobutane-1,1-dicarboxylato(2-)-kappa~2~o~1~,o~1~]platinum
STL451040
SY075575
BP-25385
azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+)
7,7-diamino-6,8-dioxa-7-platinaspiro[3.5]nonane-5,9-dione
EN300-123065

Research Excerpts

Toxicity

The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy.

ExcerptReferenceRelevance
" There were no toxic deaths."( Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa.
Baars, JW; Mandjes, I; Pinedo, HM; Richel, DJ; Rodenhuis, S; Schornagel, JH; Vlasveld, LT, 1992)		0.28
" injection of 200 mg/kg WR-2721 at 5 min prior to the administration of this combination enabled us to increase the CBDCA dose from a nontoxic level of 45 mg/kg to a normally toxic dose of 60 mg/kg in non-tumor-bearing BALB/c mice while maintaining the 5FU dose at 100 mg/kg."( Effect of WR-2721 on the toxicity and antitumor activity of the combination of carboplatin and 5-fluorouracil.
Peters, GJ; Treskes, M; van der Vijgh, WJ; van der Wilt, CL; van Laar, JA, 1992)		0.28
" Cisplatin with mannitol appeared to be less toxic than pure cisplatin, and carboplatin the least toxic."( Carboplatin and cisplatin ototoxicity in guinea pigs.
Popelár, J; Syka, J; Taudy, M; Ulehlová, L, 1992)		0.28
" The impact of culture medium composition on the expressed cellular phenotype is discussed and its consequences on the profile of toxic response due to aminoglycoside antibiotics is analyzed."( Renal proximal tubule cell cultures for studying drug-induced nephrotoxicity and modulation of phenotype expression by medium components.
Morin, JP; Toutain, H, 1992)		0.28
" CBDCA-induced MDA production was lower, compared to CDDP, which showed marked toxic effects on TEA and PAH accumulation, gluconeogenesis and glucose-6-phosphatase activity."( Nephrotoxicity of cisplatin, carboplatin and transplatin. A comparative in vitro study.
Baumann, K; Hannemann, J, 1990)		0.28
" Although CBDCA is less toxic than CDDP, it may affect hearing function if patients suffer from renal dysfunction or if the organ of Corti is vulnerable."( Ototoxicity of carboplatin in guinea pigs.
Manabe, Y; Saito, H; Saito, K; Saito, T; Tsuda, G; Wakui, S, 1989)		0.28
" The new generations of platinum, less toxic and easier to use, have raised hopes vis-à-vis its efficacy in the treatment of this tumor type."( [Use of systemic carboplatin in superficial tumors of the bladder. Preliminary phase II study (toxicity)].
Beneítez Alvarez, M; de Blas Gómez, V; Gallo Rolanía, FJ; Roa Luzuriaga, M, 1989)		0.28
"The in vivo toxic actions of cis-dichloro-1, 1-cyclo-butane-dicarboxylate platinum (II): carboplatin (CBDCA), cis-diisopropyl-ammine-transdihydroxy-dichloro platinum (IV) and iproplatin (CHIP) were compared with those of cis-diamminedichloroplatinum (II): cisplatin (CDDP) on rat bone marrow."( Evaluation of side effects of platinum complexes (CDDP, CBDCA, CHIP) on rat bone marrow.
Gal, F; Kerpel-Fronius, S; Kiss, F; Kralovánszky, J; Prajda, N, )		0.13
" Animals were treated at the respective LD50 of platin compounds, and we analyzed plasmatic testosterone level, microsomal cytochrome P-450 and platinum concentrations in the testis."( In vivo toxicity of cisplatin and carboplatin on the Leydig cell function and effect of the human choriogonadotropin.
Azouri, H; Bidart, JM; Bohuon, C, 1989)		0.28
" Carboplatin appears less toxic than cisplatin producing to date similar survival and response as a single agent."( A comparison of the toxicity and efficacy of cisplatin and carboplatin in advanced ovarian cancer. The Swons Gynaecological Cancer Group.
Adams, M; Evans, A; Franks, CR; Johansen, K; Kerby, IJ; Rocker, I, 1989)		0.28
" The LD50 value was increased from 115 to 216 mg/kg with the same DDTC schedule."( The effect of diethyldithiocarbamate on the haematological toxicity and antitumour activity of carboplatin.
Boxall, FE; Dible, SE; Harrap, KR; Siddik, ZH, 1987)		0.27
"4 times as toxic to stem cells as CBDCA."( Diethyldithiocarbamate inhibition of murine bone marrow toxicity caused by cis-diamminedichloroplatinum(II) or diammine-(1,1-cyclobutanedicarboxylato)platinum(II).
Borch, RF; Gringeri, A; Keng, PC, 1988)		0.27
" CHIP and carboplatin gave similar dose-response curves, both being much less toxic than cis-platin."( An in vitro study comparing the cytotoxicity of three platinum complexes with regard to the effect of thiol depletion.
Brock, AP; Smith, E, 1988)		0.27
" Of the platinum analogues studied, CHIP proved to be the most toxic to the small intestine."( Comparison of intestinal toxic effects of platinum complexes: cisplatin (CDDP), carboplatin (CBDCA), and iproplatin (CHIP).
Gál, F; Kerpel-Fronius, S; Kiss, F; Kralovánszky, J; Prajda, N, 1988)		0.27
" These analogues of cisplatin are 30 times less toxic than the parent compound and may be useful in the prevention of cell proliferation in the vitreous."( Retinal toxicity study of intravitreal carboplatin and iproplatin.
Nikoleit, J; Peyman, GA; Zlioba, A, 1988)		0.27
"The toxic potencies of cisplatin and carboplatin were compared in male Wistar rats."( [Experimental study on carboplatin toxicity--a comparison with cisplatin].
Aso, Y; Kawabe, K; Ohtawara, Y; Sudoko, H; Suzuki, K; Tajima, A; Usami, T, 1988)		0.27
" Dose- and time-dependent toxic responses for clinically relevant concentrations of cisplatin (10(-3)-10(-5) M) were apparent using leakage of intracellular K+, ATP, and lactate dehydrogenase (LDH) to determine cell damage."( Cisplatin nephrotoxicity: in vitro studies with precision-cut rabbit renal cortical slices.
Brendel, K; Dorr, RT; Gandolfi, AJ; Phelps, JS, 1987)		0.27
" Thus any enhancement in therapeutic efficacy with these second generation analogues can only be expected from possible decreases in toxic effects but not from superior tumor cell kill activity."( Comparative cytotoxicity between cisplatin and second generation platinum analogs.
Drewinko, B; Trujillo, JM; Yang, LY, 1985)		0.27
" All three derivatives were at least as toxic as CDDP for haemopoietic stem cells and were less active than CDDP against the mouse tumours leukaemia L1210 and osteosarcoma C22LR."( Preclinical studies on toxicity, antitumour activity and pharmacokinetics of cisplatin and three recently developed derivatives.
Atassi, G; Danguy, A; Lelieveld, P; Van der Vijgh, WJ; Van Putten, LM; Van Velzen, D; Veldhuizen, RW, 1984)		0.27
"No toxic deaths were reported."( [High-dosage chemotherapy and the autologous transplantation of peripheral hematopoietic progenitor cells in breast cancer: the initial results, analysis of toxicity and the necessary support means].
Alonso, MC; Amill, B; Bellet, M; Maroto, P; Mendoza, L; Mesía, R; Ojeda, B; Sola Rocabert, C; Tabernero, JM; Verger, G, 1995)		0.29
" This low toxic profile leads to the possibility of future trials with this chemotherapy schedule in other subgroups of patients with breast cancer."( [High-dosage chemotherapy and the autologous transplantation of peripheral hematopoietic progenitor cells in breast cancer: the initial results, analysis of toxicity and the necessary support means].
Alonso, MC; Amill, B; Bellet, M; Maroto, P; Mendoza, L; Mesía, R; Ojeda, B; Sola Rocabert, C; Tabernero, JM; Verger, G, 1995)		0.29
" In conclusion, the vinorelbine-carboplatin combination may be regarded as an active, safe regimen for the palliative treatment of advanced adenocarcinoma or large-cell carcinoma of the lung."( Efficacy and toxicity of vinorelbine-carboplatin combination in the treatment of advanced adenocarcinoma or large-cell carcinoma of the lung.
Borzellino, G; Laterza, E; Masotti, A; Morandini, G; Ricci, F; Zannini, G, )		0.13
" The objective of the present study was to determine whether, in view of its unique toxicity in the chinchilla, carboplatin has any toxic effect on the vestibular end organs."( Carboplatin ototoxicity in the chinchilla: lesions of the vestibular sensory epithelium.
Harrison, RV; Mount, RJ; Takeno, S; Wake, M, 1995)		0.29
" Tested in the range of peak concentrations in plasma of patients and at a clinically relevant fPt fraction of 10%, CDDP was not toxic for human bone marrow cells in the CFU-GM assay, whereas it was toxic at fPt fractions of 50% and 90%."( Effect of ultrafilterable platinum concentration on cisplatin and carboplatin cytotoxicity in human tumor and bone marrow cells in vitro.
de Vries, EG; Esselink, MT; Guchelaar, HJ; Meijer, C; Mulder, NH; Uges, DR; Vellenga, E, 1994)		0.29
"The nephrotoxicity of three platinum-containing antitumor agents was compared at doses that approximate the LD10 (cisplatin) or the LD50 (CI-973, carboplatin) doses."( Comparative nephrotoxicity of a novel platinum compound, cisplatin, and carboplatin in male Wistar rats.
Dominick, MA; Hoeschele, JD; Pegg, DG; Walsh, KM; Wolfgang, GH, 1994)		0.29
" Following the demonstration of the important clinical role for cisplatin, studies of the relationship between toxicity and the reactivity of the leaving groups led to the development of the less toxic but equally effective analogue, carboplatin."( Platinum complexes in cancer medicine: pharmacokinetics and pharmacodynamics in relation to toxicity and therapeutic activity.
Calvert, H; Judson, I; van der Vijgh, WJ, 1993)		0.29
" Interaction of radiation with the clinically less toxic carboplatin can be improved by prolonged low-dose carboplatin exposure before irradiation and is as potent as cisplatin in the resistant lung cancer cell line."( Carboplatin- and cisplatin-induced potentiation of moderate-dose radiation cytotoxicity in human lung cancer cell lines.
De Vries, EG; Groen, HJ; Kampinga, HH; Konings, AW; Meijer, C; Mulder, NH; Sleijfer, S, 1995)		0.29
" Although carboplatin is not toxic to the kidney, renal function markedly affects the severity of carboplatin-induced thrombocytopenia."( Comparative adverse effect profiles of platinum drugs.
McKeage, MJ, 1995)		0.29
" Fewer patients from the OND group (13%) reported adverse events compared with the MET group (21%)."( A randomised, double-blind, parallel-group study to compare the efficacy and safety of ondansetron (GR38032F) plus dexamethasone with metoclopramide plus dexamethasone in the prophylaxis of nausea and emesis induced by carboplatin chemotherapy.
Andersson, H; Capstick, V; du Bois, A; Kitchener, H; Lahousen, M; McKenna, CJ; Pinter, T; Wilkinson, JR, )		0.13
"Radiation before chemotherapy was a more toxic sequence and, surprisingly, carboplatin/etoposide administered in combination with radiotherapy was more detrimental than methotrexate."( Long-term toxicity and neuropathology associated with the sequencing of cranial irradiation and enhanced chemotherapy delivery.
Garcia, R; Mass, M; McCormick, CI; Neuwelt, EA; Pearse, HD; Remsen, LG; Roman-Goldstein, S; Sexton, G, 1997)		0.3
" The latter drugs are weakly toxic and could also attenuate the nephrotoxicity of AmB."( Potentiation of cisplatin and carboplatin cytotoxicity by amphotericin B in different human ovarian carcinoma and malignant peritoneal mesothelioma cells.
Bureau, F; Crouet, H; Gauduchon, P; Gignoux, M; Le Talaër, JY; Poulain, L; Sichel, F, 1997)		0.3
" In the present study, we investigated whether the tolerability of Ara-C or CBDCA, given at their least toxic circadian time, could be improved further with AcSDKP, a negative regulator of hemopoiesis, rhG-CSF or both."( Circadian-based effects of AcSDKP, with or without rhG-CSF on hematologic toxicity of chemotherapy in mice.
Deschamps de Paillette, E; Filipski, E; Lévi, F; Li, XM; Soulard, C, 1998)		0.3
" Our initial studies have demonstrated a direct adverse effect of individual glucocorticoids and cytotoxic agents on the proliferative capacity of rat tibial growth-plate chondrocytes in vitro."( Glucocorticoid pretreatment reduces the cytotoxic effects of a variety of DNA-damaging agents on rat tibial growth-plate chondrocytes in vitro.
Anderson, E; Eden, O; Isaksson, O; Robson, H; Shalet, S, 1998)		0.3
" Furthermore, we evaluated the times for hematopoietic reconstitution in a group of five BC patients in the high-risk adjuvant situation who underwent HD chemotherapy and hematopoietic rescue with positive/negative selected stem cells and compared it with our own data from 10 BC patients who, after identical HD therapy, received only positively selected CD34+ cells and 14 patients who, after identical HD therapy, received autografts purged by incubation with toxic ether lipids (ET-18-OCH3)."( Efficacy and safety of simultaneous immunomagnetic CD34+ cell selection and breast cancer cell purging in peripheral blood progenitor cell samples used for hematopoietic rescue after high-dose therapy.
Berdel, WE; Cassens, U; Fietz, T; Hilgenfeld, E; Hoffmann, M; Hoppe, B; Kienast, J; Knauf, WU; Koenigsmann, M; Mohr, M; Sibrowski, W; Thiel, E, 1999)		0.3
" The BAD pump was safe and effective in minimizing nausea and vomiting associated with HDC, and thus, eliminated the need for hospitalization for management of chemotherapy-induced nausea and vomiting."( Safety and efficacy of a continuous infusion, patient controlled anti-emetic pump to facilitate outpatient administration of high-dose chemotherapy.
Belt, R; Coon, J; Cord, M; Dix, S; Geller, R; Howard, S, 1999)		0.3
" There were no toxic deaths."( Epic as an effective, low toxicity salvage therapy for patients with poor risk lymphoma prior to beam high dose chemotherapy and peripheral blood progenitor cell transplantation.
Cavenagh, JD; Eden, AG; Hughes, A; Kelsey, SM; Lamont, A; McBride, NC; Mills, MJ; Newland, AC; Ward, MC, 1999)		0.3
"The adverse effects of combination chemotherapy with paclitaxel and carboplatin, including neurotoxicity, arthralgia and muscle pain, were evaluated in 21 patients (30 courses) using questionnaires of the Gynecologic Oncology Chemotherapy Joint Research Group."( [Evaluation of adverse effects including neurotoxicity of combination chemotherapy with paclitaxel and carboplatin].
Hirai, Y; Iwasaki, H; Matsui, H; Sekiya, S; Tate, S, 2000)		0.31
"The objective of this study was to evaluate potential adverse effects of paclitaxel-containing chemotherapy on the central nervous system in women with ovarian cancer."( Paclitaxel does not cause central nervous adverse effects: a prospective vigilance-controlled EEG mapping study in ovarian cancer patients.
Anderer, P; Bodner, K; Bodner-Adler, B; Hefler, L; Kaider, A; Kainz, C; Leodolter, S; Mayerhofer, K; Saletu, B, 2000)		0.31
" Additionally we investigated the extent of adverse effects due to chemotherapy with special consideration for peripheral neurotoxicity."( Paclitaxel/carboplatin as first-line chemotherapy in advanced ovarian cancer: efficacy and adverse effects with special consideration of peripheral neurotoxicity.
Bodner, K; Bodner-Adler, B; Kainz, C; Leodolter, S; Mayerhofer, K, )		0.13
" Apart from alopecia, other adverse effects were rare."( Paclitaxel/carboplatin as first-line chemotherapy in advanced ovarian cancer: efficacy and adverse effects with special consideration of peripheral neurotoxicity.
Bodner, K; Bodner-Adler, B; Kainz, C; Leodolter, S; Mayerhofer, K, )		0.13
" Neurologic toxicity, increasing with every cycle of the chemotherapy, was a clinically significant adverse effect in our study."( Paclitaxel/carboplatin as first-line chemotherapy in advanced ovarian cancer: efficacy and adverse effects with special consideration of peripheral neurotoxicity.
Bodner, K; Bodner-Adler, B; Kainz, C; Leodolter, S; Mayerhofer, K, )		0.13
" Mild to moderate fever, rigors and a dose-dependent transient transaminitis were the most common adverse events."( Intravenous infusion of a replication-selective adenovirus (ONYX-015) in cancer patients: safety, feasibility and biological activity.
Blackburn, A; Buchanan, A; Cunningham, C; Edelman, G; Kirn, D; Maples, P; Nemunaitis, J; Netto, G; Olson, S; Randlev, B; Tong, A, 2001)		0.31
"The work presents current view about toxic effects of platinum anticancer drugs."( [About side effects of platinum drugs].
Waszkiewicz, K, 2001)		0.31
" These data suggest a relationship between non-hematologic adverse events and the estimated AUC."( High-dose carboplatin and regimen-related toxicity following autologous bone marrow transplant.
Colby, C; Koziol, S; McAfee, SL; Spitzer, TR; Yeap, B, 2002)		0.31
"Paclitaxel appears to be safe to administer to cancer patients with functional hyperbilirubinemia."( Safety of paclitaxel in a patient with ovarian cancer and hyperbilirubinemia due to Rotor's syndrome.
Argon, A; Aydiner, A; Saip, P; Tas, F; Topuz, E, 2002)		0.31
"Weekly paclitaxel and carboplatin is safe and feasible in outpatients and a high dose intensity can be achieved."( Feasibility and toxicity of weekly Paclitaxel-Carboplatin in 131 patients with pretreated and non-pretreated solid tumors.
Boehme, C; Cerny, T; D'Addario, G; Morant, R, 2002)		0.31
" No transfusion reactions or any serious adverse event was recorded during autologous platelet transfusions."( Safety and efficacy of transfusions of autologous cryopreserved platelets derived from recombinant human thrombopoietin to support chemotherapy-associated severe thrombocytopenia: a randomised cross-over study.
Broemeling, LD; Bueso-Ramos, C; Connor, J; Currie, LM; Folloder, J; Freedman, RS; Hoots, WK; Kavanagh, JJ; Lichtiger, B; Narvios, AB; Vadhan-Raj, S; Verschraegen, CF, 2002)		0.31
" This uncommon adverse effect of carboplatin and paclitaxel alone or combined is discussed and the literature reviewed."( Bilateral irreversible hearing loss associated with the combination of carboplatin and paclitaxel chemotherapy: a unusual side effect.
Casale, M; Di Peco, V; Firrisi, L; Greco, F; Onori, N; Salvinelli, F; Santini, D; Tonini, G; Vincenzi, B, 2003)		0.32
" They share some structural similarities; however, there are marked differences between them in therapeutic use, pharmacokinetics and adverse effects profiles [1-4]."( Toxicity of platinum compounds.
Hartmann, JT; Lipp, HP, 2003)		0.32
" The toxic death rate was 1%."( Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience.
Baars, JW; Holtkamp, MJ; Rodenhuis, S; Schornagel, JH; Schrama, JG, 2003)		0.32
" Results of the psychometric analyses supported the use of this subscale for measuring the unwanted adverse consequences of effective cancer therapies."( Measuring the side effects of taxane therapy in oncology: the functional assesment of cancer therapy-taxane (FACT-taxane).
Cella, D; Hudgens, S; Peterman, A; Socinski, MA; Webster, K, 2003)		0.32
"Future research might examine this question of competing benefits as a potential aid to decision-making regarding the administration of toxic therapies in the setting of advanced disease."( Measuring the side effects of taxane therapy in oncology: the functional assesment of cancer therapy-taxane (FACT-taxane).
Cella, D; Hudgens, S; Peterman, A; Socinski, MA; Webster, K, 2003)		0.32
" Although our experience is limited, we suggest that, under anesthesiologic surveillance and providing immunologic blockade, the replacement of carboplatin salvage therapy with cisplatin can be considered a safe therapeutic strategy in patients who cannot continue carboplatin due to allergic reactions."( Safety of cisplatin after severe hypersensitivity reactions to carboplatin in patients with recurrent ovarian carcinoma.
Barletta, E; De Vivo, R; Di Maio, M; Esposito, G; Greggi, S; Iaffaioli, VR; Losito, S; Ottaiano, A; Pignata, S; Prato, R; Scala, F; Tambaro, R, )		0.13
" This report shows that conventional-dose palliative chemotherapy regimens may be safe and effective after failure of high-dose chemotherapy."( Palliative chemotherapy after failure of high-dose chemotherapy in breast cancer--toxicity and efficacy.
Baars, JW; de Boer, MM; Rodenhuis, S; Schornagel, JH; Schrama, JG, )		0.13
" In addition, CED of carboplatin or gemcitabine to tumors in this glioma model is safe and has potent antitumor effects."( Safety and efficacy of convection-enhanced delivery of gemcitabine or carboplatin in a malignant glioma model in rats.
Degen, JW; Lonser, RR; Oldfield, EH; Vortmeyer, AO; Walbridge, S, 2003)		0.32
" Adverse events with grade 3 or above hematologic toxicity were oligochromemia (M: 24."( [Paclitaxel plus carboplatin in ovarian cancer-comparison of adverse effects between monthly and weekly administration].
Fujii, T; Komatsu, M; Kumagai, M; Kusuda, T; Naitou, H; Shinkou, S; Takehara, K, 2004)		0.32
" The association of carboplatin AUC = 6 and weekly paclitaxel 100 mg/m2 proved to be manageable, active and extremely safe even in elderly patients (one third of all patients in our cohort)."( The combination of carboplatin and weekly paclitaxel: a safe and active regimen in advanced non small-cell lung cancer patients. A phase I-II study.
Barduagni, M; Ceribelli, A; Cognetti, F; Cortesi, E; De Marco, S; De Marinis, F; Fabi, A; Facciolo, F; Ferraresi, V; Gabriele, A; Gamucci, T; Pellicciotta, M; Saltarelli, R, 2004)		0.32
" Neurotoxicity is the predominant side effect and is dose-dependent."( Toxicity and cerebrospinal fluid levels of carboplatin chronically infused into the brainstem of a primate.
Carson, BS; Gillis, EM; Guarnieri, M; Jallo, GI; Johnson, RM; Kiely, A; Liu, YJ; Storm, P; Strege, RJ, 2004)		0.32
" Nephrotoxicity is a common and relevant adverse effect that occurs especially in cisplatin therapy."( Nephrotoxicity of platinum complexes is related to basolateral organic cation transport.
Gekle, M; Ludwig, T; Oberleithner, H; Riethmüller, C; Schwerdt, G, 2004)		0.32
" Thus, this regimen is safe as regards clinically significant lung toxicity."( A prospective study on lung toxicity in patients treated with gemcitabine and carboplatin: clinical, radiological and functional assessment.
Dafni, U; Dimopoulos, MA; Dimopoulou, I; Efstathiou, E; Kastritis, E; Lyberopoulos, P; Moulopoulos, LA; Papadimitriou, C; Roussos, C; Samakovli, A, 2004)		0.32
" TMJ is a safe and effective regimen when used as a part of autologous stem cell transplant for patients with HD and NHL."( High dose chemotherapy with thiotepa, mitoxantrone and carboplatin (TMJ) followed by autologous stem cell support in 100 consecutive lymphoma patients in a single centre: analysis of efficacy, toxicity and prognostic factors.
Ahmed, T; Hoang, A; Kancherla, R; Liu, D; Qureshi, Z; Seiter, K; Waheed, F, 2004)		0.32
"With a 6-year follow-up the combination of VP16 and carboplatin given at conventional doses is safe on renal and hearing functions in infants with unresectable neuroblastomas treated according to SFOP NB90."( Long-term renal and hearing toxicity of carboplatin in infants treated for localized and unresectable neuroblastoma: results of the SFOP NBL90 study.
Bergeron, C; Chastagner, P; Desfachelles, AS; Dubourg, L; Dusol, F; Edan, C; Froehlich, P; Mechinaud, F; Pautard, B; Plantaz, D; Plouvier, E; Rubie, H, 2005)		0.33
" L61 was toxic to the cells with or without drug (viability<3."( Enhancement of carboplatin toxicity by Pluronic block copolymers.
Exner, AA; Krupka, TM; Scherrer, K; Teets, JM, 2005)		0.33
" Agreement between the usually reported National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) and ASHA criteria was inadequate."( Ototoxicity in children receiving platinum chemotherapy: underestimating a commonly occurring toxicity that may influence academic and social development.
Knight, KR; Kraemer, DF; Neuwelt, EA, 2005)		0.33
"Ototoxicity is a common side effect of platinum-based chemotherapy."( Ototoxicity of carboplatin delivered locally in a monkey brainstem.
Carey, JP; Carson, BS; Cooper, T; Guarnieri, M; Jallo, GI, )		0.13
"Ototoxicity is a typical dose-limiting side effect of cancer chemotherapy with cisplatin but much less so with carboplatin."( High accumulation of platinum-DNA adducts in strial marginal cells of the cochlea is an early event in cisplatin but not carboplatin ototoxicity.
Lautermann, J; Liedert, B; Seiler, F; Thomale, J; Thomas, JP, 2006)		0.33
" Derivatives of NICE showed different renal epithelial toxic profiles and effects on cancer cells."( New imidazole-coordinated chemotherapeutics with low epithelial toxicity.
Bertram, H; Fakih, S; Krebs, B; Ludwig, T; Oberleithner, H, 2006)		0.33
" No toxic death was recorded."( Safety of a 3-weekly schedule of carboplatin plus pegylated liposomal doxorubicin as first line chemotherapy in patients with ovarian cancer: preliminary results of the MITO-2 randomized trial.
Annunziata, A; Breda, E; D'Arco, AM; De Vivo, R; Del Gaizo, F; Di Maio, M; Ferro, A; Gebbia, V; Musso, P; Naglieri, E; Natale, D; Perrone, F; Pignata, S; Pisano, C; Rossi, E; Savarese, A; Scambia, G; Scollo, P; Signoriello, G; Sorio, R, 2006)		0.33
" In this phase I/II study, we examined if administration of IFN-gamma is also safe in combination with the current standard treatment, paclitaxel and carboplatin."( Interferon-gamma in combination with carboplatin and paclitaxel as a safe and effective first-line treatment option for advanced ovarian cancer: results of a phase I/II study.
Estermann, K; Hausmaninger, H; Marth, C; Mueller-Holzner, E; Pelzer, A; Petru, E; Windbichler, GH, )		0.13
"The objective of this study was to evaluate prospectively the acute and late adverse effects of taxane/carboplatin neoadjuvant chemotherapy and 3-dimensional, conformal radiotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC)."( Toxicity and outcome of a phase II trial of taxane-based neoadjuvant chemotherapy and 3-dimensional, conformal, accelerated radiotherapy in locally advanced nonsmall cell lung cancer.
Dickson, J; Lyn, BE; Rojas, AM; Saunders, MI; Shah, N; Williams, FJ; Wilson, EM, 2006)		0.33
" Radiation-induced, early, adverse effects were assessed during the first 9 weeks from the start of radiotherapy, and late effects were assessed from 3 months onward."( Toxicity and outcome of a phase II trial of taxane-based neoadjuvant chemotherapy and 3-dimensional, conformal, accelerated radiotherapy in locally advanced nonsmall cell lung cancer.
Dickson, J; Lyn, BE; Rojas, AM; Saunders, MI; Shah, N; Williams, FJ; Wilson, EM, 2006)		0.33
" However, it was repeatedly shown that the sequence of 5-FU followed by CDDP is more active and less toxic in tumor-bearing animals."( Schedule-dependent antitumor activity and toxicity of combinations of 5-fluorouracil and cisplatin/carboplatin against L1210 leukemia-bearing mice.
Fujimoto, S, 2006)		0.33
" The major adverse reactions relative to rhIL-11 treatment were fatigue, myalgia/arthralgia, ache, headache, palpitation, edema and fever, most of which could be relieved automatically without any specific treament."( [Effectiveness and safety of recombinant human interleukin-11 in the treatment of chemotherapy-induced thrombocytopenia].
Chen, WG; Du, LL; Lei, W; Liang, J; Ma, XZ; Xu, M, 2006)		0.33
"rhIL-11 is safe and effective for chemotherapy-induced thrombocytopenia with mild and manageable side effects."( [Effectiveness and safety of recombinant human interleukin-11 in the treatment of chemotherapy-induced thrombocytopenia].
Chen, WG; Du, LL; Lei, W; Liang, J; Ma, XZ; Xu, M, 2006)		0.33
" We then show that aging carboplatin in carbonate produces compounds that are more toxic to human neuroblastoma (SK-N-SH), proximal renal tubule (HK-2) and Namalwa-luc Burkitt's lymphoma (BL) cells than carboplatin alone."( Role of carbonate in the cytotoxicity of carboplatin.
Dabrowiak, JC; Di Pasqua, AJ; Dubowy, RL; Goodisman, J; Kerwood, DJ; Toms, BB, 2007)		0.34
"We performed a retrospective study to examine the protective effect of low-dose dexamethasone (DEX) on delayed adverse events induced by carboplatin (CBDCA)-based combination chemotherapy in patients with thoracic tumors."( Preventive effects of low-dose dexamethasone for delayed adverse events induced by carboplatin-based combination chemotherapy.
Bandoh, S; Doi, C; Fukuoka, N; Houchi, H; Ishida, T; Kanaji, N; Kawazoe, H; Takiguchi, Y; Tanaka, H, 2007)		0.34
" There were no reports of Grade >/=3 amifostine-related adverse events."( Efficacy and safety of subcutaneous amifostine in minimizing radiation-induced toxicities in patients receiving combined-modality treatment for squamous cell carcinoma of the head and neck.
Christie, D; Kennedy, T; Law, A; Pellitteri, P; Wood, C; Yumen, O, 2007)		0.34
" In addition, decreases in hemoglobin and thrombopenia were observed in 10 and 2 patients, respectively, but both adverse events were mild (< Grade 3) and could be controlled on an outpatient basis in all cases."( [Safety evaluation of adjuvant chemotherapy by weekly paclitaxel combined with weekly carboplatin in patients with postoperative non-small cell lung cancer].
Hirose, T; Hirose, Y; Kajikawa, A; Kenzaki, K; Nagao, T; Sugimoto, T; Sumi, T; Yoshida, M, 2007)		0.34
" Nearly all patients (94%) suffered at least one grade 3 or worse adverse event, including 3 treatment-related deaths."( Paclitaxel, carboplatin, 5-fluorouracil, and radiation for locally advanced esophageal cancer: phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044).
Alberts, SR; Fitch, TR; Foster, NR; Jatoi, A; Lair, BS; Martenson, JA; McLeod, HL; Moore, DF; Nichols, F; Tschetter, LK, 2007)		0.34
"This 3-drug, multimodality approach yielded a pathologic complete response rate of 35%, but the severe adverse event rate was high."( Paclitaxel, carboplatin, 5-fluorouracil, and radiation for locally advanced esophageal cancer: phase II results of preliminary pharmacologic and molecular efforts to mitigate toxicity and predict outcomes: North Central Cancer Treatment Group (N0044).
Alberts, SR; Fitch, TR; Foster, NR; Jatoi, A; Lair, BS; Martenson, JA; McLeod, HL; Moore, DF; Nichols, F; Tschetter, LK, 2007)		0.34
"To analyse carboplatin dosage in cancer patients in order to establish whether they are over- or underdosed in comparison to the theoretical dose calculations during the first cycle of chemotherapy and to find a relationship between the dosage in the first cycle and dose reduction in subsequent cycles, as a result of adverse effects related to the same."( [Retrospective analysis of the carboplatin dosage and relationship with toxicity in cancer patients].
Castellanos Clemente, Y; Díez Fernández, R; García Palomo, M; Hernández Muniesa, B; Iglesias Bolaños, AM; Martínez Sesmero, JM, )		0.13
"No early or toxic deaths were observed."( [Combination of carboplatin and gemcitabine is a safe and feasible regimen in adjuvant therapy for stage II and IIIA NSCLC].
Kameda, A; Minami, K; Miyahara, E; Noso, Y; Suzuki, T; Tsutani, Y, 2008)		0.35
"In the present study, the combination of carboplatin and gemcitabine has been a safe and feasible regimen in adjuvant therapy for stage II and IIIA NSCLC."( [Combination of carboplatin and gemcitabine is a safe and feasible regimen in adjuvant therapy for stage II and IIIA NSCLC].
Kameda, A; Minami, K; Miyahara, E; Noso, Y; Suzuki, T; Tsutani, Y, 2008)		0.35
" Several other severe nonhematological adverse effects were well tolerated and easily managed."( A pilot study evaluating the efficacy and toxicity of biweekly gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant epithelial ovarian cancer.
Aydiner, A; Derin, D; Guney, N; Tas, F; Topuz, E, 2008)		0.35
"A biweekly schedule of gemcitabine combined with PLD is an active and safe chemotherapy regimen with acceptable and easily manageable toxicities in women with recurrent platinum-resistant ovarian cancer."( A pilot study evaluating the efficacy and toxicity of biweekly gemcitabine and pegylated liposomal doxorubicin in recurrent platinum-resistant epithelial ovarian cancer.
Aydiner, A; Derin, D; Guney, N; Tas, F; Topuz, E, 2008)		0.35
"Several antineoplastic drugs induce severe toxic damage of the peripheral nervous system and chemotherapy-induced peripheral neurotoxicity (CIPN) can be dose limiting."( Neurotoxic effects of antineoplastic drugs: the lesson of pre-clinical studies.
Cavaletti, G; Marmiroli, P; Nicolini, G, 2008)		0.35
"The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen."( Weekly carboplatin reduces toxicity during synchronous chemoradiotherapy for Merkel cell carcinoma of skin.
Dickie, G; Harvey, J; Keller, J; O'Brien, P; Poulsen, M; Rischin, D; Tripcony, L; Walpole, E, 2008)		0.35
" Pharmacogenetic approaches can identify patients who are at risk of experiencing toxic side effects in high-dose chemotherapy."( Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin.
Beijnen, JH; Ekhart, C; Huitema, AD; Rodenhuis, S; Smits, PH, 2008)		0.35
" In the previous five cycles of ifosfamide, carboplatin, and etoposide, the patient had no problems with the neurotoxic adverse effects associated with ifosfamide use."( Possible contribution of aprepitant to ifosfamide-induced neurotoxicity.
Jarkowski, A, 2008)		0.35
" Reports on adverse effects of concurrent chemo- and radiotherapy in the veterinary literature are scant."( Adverse effects of concurrent carboplatin chemotherapy and radiation therapy in dogs.
Hume, KR; Johnson, JL; Williams, LE, )		0.13
"To report adverse hematologic and gastrointestinal effects of combined carboplatin and radiation therapy in dogs."( Adverse effects of concurrent carboplatin chemotherapy and radiation therapy in dogs.
Hume, KR; Johnson, JL; Williams, LE, )		0.13
" Sequential dose intense ifosfamide, etoposide, carboplatin +/- rituximab was more toxic and no more effective than the same drugs given in a conventional fashion."( Sequential high-dose ifosfamide, carboplatin and etoposide with rituximab for relapsed Hodgkin and large B-cell non-Hodgkin lymphoma: increased toxicity without improvement in progression-free survival.
Beaven, AW; Chao, N; Gabriel, DA; Garcia, RA; Gockerman, JP; Moore, DT; Rizzieri, DA; Serody, JS; Shea, TC, 2009)		0.35
" Records were reviewed for patient age, BSA, diagnosis, stage, standardized and actual doses for each cycle, adverse drug reactions, and dosing modifications."( Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.
Dizon, DS; Schwartz, J; Toste, B, 2009)		0.35
"Addition of bevacizumab to various chemotherapy agents or erlotinib in patients with NSCLC and treated brain metastases seems to be safe and is associated with a low incidence of CNS hemorrhage."( Safety of bevacizumab in patients with non-small-cell lung cancer and brain metastases.
Akerley, W; Compton, P; Huang, JE; Kolb, MM; Langer, CJ; Socinski, MA; Wang, L, 2009)		0.35
" Severe adverse events possibly related to F included fatigue, diarrhea, hyperglycemia, gamma glutamyl transpeptidase elevation, and thrombocytopenia (one case each)."( Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel and carboplatin.
Cardenal, F; Cohen, RB; Demers, L; Eisenberg, PD; Garland, L; Gualberto, A; Haluska, P; Hixon, ML; Karp, DD; Langer, CJ; Leitzel, K; Lipton, A; Paz-Ares, LG; Pollak, MN; Terstappen, LW; Yin, D, 2009)		0.35
"This safety lead-in study examined the pharmacokinetic and adverse event profile of combining enzastaurin with paclitaxel plus carboplatin as first-line therapy for the treatment of advanced-stage ovarian cancer and primary peritoneal carcinoma."( Carboplatin and paclitaxel in combination with oral enzastaurin in advanced ovarian or primary peritoneal cancer: results from a safety lead-in study.
Amant, F; Bauknecht, T; Darstein, C; Kania, M; Michel, AL; Musib, L; Oskay-Oezcelik, G; Sehouli, J; Vergote, I, 2009)		0.35
" Adverse events were graded according to the Common Terminology Criteria for Adverse Events v3."( Carboplatin and paclitaxel in combination with oral enzastaurin in advanced ovarian or primary peritoneal cancer: results from a safety lead-in study.
Amant, F; Bauknecht, T; Darstein, C; Kania, M; Michel, AL; Musib, L; Oskay-Oezcelik, G; Sehouli, J; Vergote, I, 2009)		0.35
"There were 5 serious adverse events in 4 of 11 patients: soft tissue injury, wound infection, intestinal fistula, clostridial infection, and anemia."( Carboplatin and paclitaxel in combination with oral enzastaurin in advanced ovarian or primary peritoneal cancer: results from a safety lead-in study.
Amant, F; Bauknecht, T; Darstein, C; Kania, M; Michel, AL; Musib, L; Oskay-Oezcelik, G; Sehouli, J; Vergote, I, 2009)		0.35
" In this study, we compared the dosage of carboplatin (CBDCA) calculated using MDRD with that calculated by conservative creatinine clearance (Ccr), and investigated the actual dosage given and the incidence of its adverse effects."( [Clinical evaluation of calculating carboplatin doses using modification of diet in renal disease (MDRD) estimate and adverse events].
Adachi, S; Kimura, M; Matsumoto, R; Matsuoka, T; Nakao, T; Okada, K; Tanaka, Y; Usami, E; Yasuda, T; Yoshimura, T, 2009)		0.35
" Thirty-five percent of patients on PCB + S required S dose reduction, 52% required S treatment interruption, and 59% discontinued S because of adverse events, most frequently hematologic events (neutropenia, thrombocytopenia, and leukopenia) and fatigue."( Safety and efficacy of combining sunitinib with bevacizumab + paclitaxel/carboplatin in non-small cell lung cancer.
Kolb, MM; Kozloff, MF; Samant, M; Scappaticci, FA; Socinski, MA, 2010)		0.36
"Weekly administration of paclitaxel /docetaxel is a safe and active protocol for advanced NSCLCs."( Weekly paclitaxel/ docetaxel combined with a platinum in the treatment of advanced non-small cell lung cancer: a study on efficacy, safety and pre-medication.
Huang, XE; Jiang, W; Li, C; Lin, Y; Shi, MQ; Shu, YQ; Sunh, WL; Ye, Z; Zhang, Q; Zhou, JN, 2009)		0.35
" The purpose of this study was to validate this grading system by assessing its correspondence to audiology treatment recommendations and comparing it with the currently utilized Common Terminology Criteria for Adverse Events (CTCAE)."( Practical grading system for evaluating cisplatin ototoxicity in children.
Chang, KW; Chinosornvatana, N, 2010)		0.36
"5%) and grade 4 non-hematologic adverse events (n = 2) were rare, with no treatment-related deaths."( Efficacy and safety of gemcitabine, carboplatin, dexamethasone, and rituximab in patients with relapsed/refractory lymphoma: a prospective multi-center phase II study by the Puget Sound Oncology Consortium.
Daniels, JT; Garrison, MA; Gjerset, GF; Gooley, TA; Gopal, AK; Lonergan, M; Murphy, AE; Pagel, JM; Petersdorf, SH; Press, OW; Shustov, AR; Smith, JC, 2010)		0.36
" Grade III/IV adverse events were (n; %): leucopenia (5; 22%), neutropenia (7; 30%), thrombocytopenia (3; 13%) anaemia (1; 4%), peripheral sensory neuropathy (2; 9%), fatigue (1; 4%), vomiting (1; 4%) and myalgia (1; 4%)."( A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours.
Buhl-Jensen, P; Crowley, E; de Bono, JS; Engelholm, SA; Knoblauch, P; Lassen, U; Molife, LR; Penson, RT; Sinha, R; Sorensen, M; Tjornelund, J; Vidal, L, 2010)		0.36
" The use of most cytotoxic agents is associated with potential hypersensitivity reactions, and the constant increase of their administration has caused an increase in incidence of these adverse effects, thus becoming a relevant problem for clinicians."( The complex clinical picture of presumably allergic side effects to cytostatic drugs: symptoms, pathomechanism, reexposure, and desensitization.
Pagani, M, 2010)		0.36
"Ambulatory chemotherapy has now been a popular way of treatment in developed countries, for its less medical costs and incidence of adverse events."( [Safety analysis of ambulatory chemotherapy in lung cancer].
Chen, Z; Feng, Y; Lu, S; Shi, Y; Song, Z; Xu, L, 2010)		0.36
"Medical data including performance status, cycles of chemotherapy, pathologic type, adverse events in hospital and adverse events after discharge from hospital."( [Safety analysis of ambulatory chemotherapy in lung cancer].
Chen, Z; Feng, Y; Lu, S; Shi, Y; Song, Z; Xu, L, 2010)		0.36
" The most commonly reported adverse events across all study arms (including placebo) were nausea and alopecia and eltrombopag was generally well tolerated."( A randomized, double-blind, placebo-controlled, dose ranging study to assess the efficacy and safety of eltrombopag in patients receiving carboplatin/paclitaxel for advanced solid tumors.
Bondarenko, IN; Jagiello-Gruszfeld, A; Kellum, A; Messam, C; Mostafa Kamel, Y; Patwardhan, R, 2010)		0.36
"0%) experienced grade 3 adverse events, including five with hypertension; five patients experienced grade 4 adverse events (dyspnea, PH, basal ganglia infarction, cerebral ischemia, and pain)."( BRIDGE: an open-label phase II trial evaluating the safety of bevacizumab + carboplatin/paclitaxel as first-line treatment for patients with advanced, previously untreated, squamous non-small cell lung cancer.
Azzoli, C; Fang, L; Faoro, L; Hainsworth, JD; Huang, JE; Karlin, D; Russell, K, 2011)		0.37
" However, each agent differs in its efficacy and adverse effects, although the molecular mechanism involved is unclear."( Organic cation transporter OCT/SLC22A and H(+)/organic cation antiporter MATE/SLC47A are key molecules for nephrotoxicity of platinum agents.
Inui, K; Yonezawa, A, 2011)		0.37
"To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma."( [Clinical efficacy and adverse effects of taxol plus carboplatin or gemcitabine plus carboplatin in patients with advanced non-small-cell lung carcinoma].
Wang, XY; Zhao, YL, 2010)		0.36
" The incidence of clinically significant adverse events (grade ≥3) of special interest was relatively low in this population (15."( Safety and efficacy of first-line bevacizumab with chemotherapy in Asian patients with advanced nonsquamous NSCLC: results from the phase IV MO19390 (SAiL) study.
Au, JS; Chang, GC; Cheng, AC; Tsai, CM; Wu, YL; Zhou, C, 2011)		0.37
" The pharmacokinetics of both drugs were analyzed, and both adverse events and treatment response were monitored."( Safety and pharmacokinetic study of nab-paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer.
Kubota, K; Murakami, H; Nakagawa, K; Nogami, N; Ohe, Y; Okamoto, I; Ono, K; Yamamoto, N; Yamaya, H, 2012)		0.38
"The FDA's adverse event reporting system, AERS, with optimized data mining tools is useful to authorize potential associations between platinum agents and hypersensitivity reactions."( Platinum agent-induced hypersensitivity reactions: data mining of the public version of the FDA adverse event reporting system, AERS.
Kadoyama, K; Niijima, S; Okuno, Y; Sakaeda, T; Seki, K; Shiraishi, Y; Yabuuchi, H, 2011)		0.37
" In all, 19 out of 60 patients discontinued cediranib or placebo during chemotherapy because of adverse events/intercurrent illness (n=9); disease progression (n=1); death (n=3); patient decision (n=1); administrative reasons (n=1); and multiple reasons (n=4)."( Initial toxicity assessment of ICON6: a randomised trial of cediranib plus chemotherapy in platinum-sensitive relapsed ovarian cancer.
Griffin, CL; Hirte, H; Ledermann, JA; Parmar, MK; Qian, W; Raja, FA; Swart, AM, 2011)		0.37
"Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to confirm platinum agent-associated adverse events, and to clarify the rank-order of these drugs in terms of susceptibility."( Adverse event profiles of platinum agents: data mining of the public version of the FDA adverse event reporting system, AERS, and reproducibility of clinical observations.
Kadoyama, K; Okuno, Y; Sakaeda, T, 2011)		0.37
", drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean."( Adverse event profiles of platinum agents: data mining of the public version of the FDA adverse event reporting system, AERS, and reproducibility of clinical observations.
Kadoyama, K; Okuno, Y; Sakaeda, T, 2011)		0.37
"The results obtained herein were consistent with clinical observations, suggesting the usefulness of the FDA's adverse event reporting system, AERS, and the data mining method used herein."( Adverse event profiles of platinum agents: data mining of the public version of the FDA adverse event reporting system, AERS, and reproducibility of clinical observations.
Kadoyama, K; Okuno, Y; Sakaeda, T, 2011)		0.37
" The incidence of adverse events (AEs) of special interest was similar for elderly and younger patients (any grade bleeding 38."( Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer: safety of avastin in lung trial (MO19390).
Crinò, L; Felip, E; Franke, F; Gorbunova, V; Groen, H; Jiang, GL; Laskin, J; Reck, M; Schneider, CP, 2012)		0.38
" Adverse effects (AEs), objective response rate (ORR), median time to progression (TTP), and overall survival (OS) were measured."( [Evaluation of efficacy and safety of bevacizumab combined with chemotherapy for Chinese patients with advanced non-small cell lung cancer].
Li, L; Wang, M; Zhang, L; Zhao, X; Zhong, W, 2012)		0.38
" To prevent adverse effects, improve delivery, and optimize the tumor response to treatment in combination with radiotherapy, a potential approach consists of incorporating the platinum agent in a liposome."( Glioblastoma treatment: bypassing the toxicity of platinum compounds by using liposomal formulation and increasing treatment efficiency with concomitant radiotherapy.
Charest, G; Fortin, D; Mathieu, D; Paquette, B; Sanche, L, 2012)		0.38
" The TC combined with endostar treatment has good safety and tolerability, improves the quality of life, and not increases serious adverse effects and toxicity for patients with advanced NSCLC."( [A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].
Bai, CX; Gu, AQ; Guo, SL; Han, BH; Jiang, LY; Jin, B; Jin, XQ; Liu, WC; Luo, Y; Shen, J; Shi, CL; Wang, HM; Xiu, QY; Zhang, Y; Zhao, YZ; Zhou, JY; Zhuang, ZX, 2011)		0.37
"This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy."( Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track.
Balmer, A; Beck-Popovic, M; Gaillard, MC; Moulin, AP; Munier, FL; Soliman, S, 2012)		0.38
" Unfortunately, recent clinical reports associate adverse vascular toxicities with SSIOAC using melphalan, the most commonly used chemotherapeutic."( Intra-ophthalmic artery chemotherapy triggers vascular toxicity through endothelial cell inflammation and leukostasis.
Haik, BG; Jackson, JS; Johnson, D; Mandrell, TD; Soderland, C; Steinle, JJ; Stewart, CF; Thompson, KE; Toutounchian, J; Wang, F; Williams, JS; Wilson, MW; Yates, CR; Zhang, Q, 2012)		0.38
" Furthermore, carboplatin provokes a significant GBM cell kill at concentrations that are not toxic to normal brain."( An evaluation of the safety and feasibility of convection-enhanced delivery of carboplatin into the white matter as a potential treatment for high-grade glioma.
Bienemann, A; Castrique, E; Cox, A; Gill, S; McLeod, C; Pugh, J; Taylor, H; White, E; Wyatt, M, 2012)		0.38
"Replacing carboplatin with nedaplatin provided a safe and efficacious approach to manage carboplatin hypersensitivity."( Safety and efficacy of substituting nedaplatin after carboplatin hypersensitivity reactions in gynecologic malignancies.
Matsumoto, K; Michikami, H; Minaguchi, T; Ochi, H; Okada, S; Oki, A; Onuki, M; Satoh, T; Yoshikawa, H, 2013)		0.39
" Dose-limiting toxic effects, adverse events (AEs), pharmacokinetics, and anti-volociximab antibodies were assessed."( Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer.
Almokadem, S; Belani, CP; Besse, B; Chao, DT; Fang, Y; Soria, JC; Tsao, LC, 2013)		0.39
" Adverse events of grade 1/2 were common."( [Docetaxel plus carboplatin versus EC-T as adjuvant chemotherapy for triple-negative breast cancer: safety data from a phase III randomized open-label trial].
Fan, Y; Li, Q; Ma, F; Wang, JY; Wang, WM; Xu, BH; Yuan, P; Zhang, P, 2012)		0.38
"Both EC-T and TP regimens as adjuvant chemotherapy are safe and tolerable for the treatment of triple-negative breast cancer patients, while the TP regimen has advantages with less grade III/IV alopecia and leukopenia."( [Docetaxel plus carboplatin versus EC-T as adjuvant chemotherapy for triple-negative breast cancer: safety data from a phase III randomized open-label trial].
Fan, Y; Li, Q; Ma, F; Wang, JY; Wang, WM; Xu, BH; Yuan, P; Zhang, P, 2012)		0.38
" All drugs were more toxic on CFU-GM progenitor cells of insulin resistant Zucker rats than on CFU-GM cells of the control strain."( Toxicity of cytotoxic agents to granulocyte-macrophage progenitors is increased in obese Zucker and non-obese but insulin resistant Goto-Kakizaki rats.
Benkő, I; Benkő, K; Géresi, K; Megyeri, A; Peitl, B; Szabó, B; Szilvássy, Z, 2012)		0.38
" Late-onset adverse events including two cases of cytomegalovirus pneumonia and one of interstitial pneumonia were observed."( Safety and feasibility of high-dose ranimustine (MCNU), carboplatin, etoposide, and cyclophosphamide (MCVC) therapy followed by autologous stem cell transplantation for malignant lymphoma.
Harigae, H; Hirokawa, M; Ishida, Y; Ishizawa, K; Ito, J; Kameoka, Y; Kato, Y; Murai, K; Noji, H; Sasaki, O; Sawada, K; Shichishima, T; Tajima, K; Takahashi, N, 2012)		0.38
" Partial response was achieved after two courses of the CBDCA and paclitaxel combination chemotherapy, with adverse events of Grade 3 neutropenia and Grade 3 peripheral neuropathy observed in each course after the second course of chemotherapy."( [Safe and effective administration of carboplatin-based chemotherapy in a patient undergoing hemodialysis with cancer of unknown primary by monitoring observed AUC of carboplatin-a case report].
Hayashi, R; Ikai, Y; Kimura, K; Komatsu, H; Kondo, M; Kuroda, J; Uegaki, S; Yoshida, A; Yoshida, T, 2012)		0.38
"The aim of this study was to assess retinal toxicity in a rabbit model after carboplatin delivered as repeated transcorneal intravitreal injection, in order to determine the highest possible safe dose for use in human retinoblastoma "seeding" tumor chemotherapy."( Retinal toxicity after repeated intravitreal carboplatin injection into rabbit eyes.
Darsova, D; Klapkova, E; Kodetova, D; Kukacka, J; Lestak, J; Malis, J; Pochop, P; Uhlik, J; Vajner, L, 2014)		0.4
"008 mg of carboplatin is probably the highest possible safe dose for the treatment of retinoblastoma patients."( Retinal toxicity after repeated intravitreal carboplatin injection into rabbit eyes.
Darsova, D; Klapkova, E; Kodetova, D; Kukacka, J; Lestak, J; Malis, J; Pochop, P; Uhlik, J; Vajner, L, 2014)		0.4
" Thus highly efficient immunotherapy based on DC-Ag-CIK cells may be a potential effective and safe mean of treating RB especially to patients where traditional chemical therapy has failed."( Cytokine-induced killer cells co-cultured with complete tumor antigen-loaded dendritic cells, have enhanced selective cytotoxicity on carboplatin-resistant retinoblastoma cells.
Chen, XM; Kunda, PE; Lin, JW; Liu, QL; Liu, T; Wang, H; Wang, YF, 2013)		0.39
" Serious adverse events (AEs) occurring in 20/37 patients included neutropenia (n = 5), diarrhea (n = 4), pulmonary embolism (n = 3), and simultaneous dehydration, acute renal failure, and febrile neutropenia (n = 2)."( A phase I trial to determine the safety, pharmacokinetics, and pharmacodynamics of intercalated BMS-690514 with paclitaxel/carboplatin (PC) in advanced or metastatic solid malignancies.
Adjei, AA; Belani, CP; Chow, LQ; Dy, GK; Fortin, C; Gupta, A; Jonker, DI; Laurie, SA; Nicholas, G; Park, JS; Patricia, D; Sbar, EI; Zhang, S, 2013)		0.39
" Of the grade ≥3 treatment-related adverse events, anemia and thrombocytopenia were more common in nab-PC arm, but sensory neuropathy was less common."( Efficacy and safety of weekly nab-paclitaxel plus carboplatin in patients with advanced non-small cell lung cancer.
Ichinose, Y; Kasahara, K; Mitsudomi, T; Negoro, S; Nogami, N; Ohmatsu, H; Okamoto, I; Sakai, H; Satouchi, M; Takeda, K; Yamamoto, N, 2013)		0.39
" We propose that a primary application of a low dose of a chemotherapeutic drug that is able to attack the tumor, and a subsequent treatment with highly effective immunotherapy based on DC-Ag-CIK cells could be a safe and selective treatment for RB."( Tandem therapy for retinoblastoma: immunotherapy and chemotherapy enhance cytotoxicity on retinoblastoma by increasing apoptosis.
Kunda, PE; Liu, Q; Liu, T; Liu, Y; Wang, H; Wang, Y, 2013)		0.39
" Diarrhea was the most common adverse event."( Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).
Chia, S; Cortés, J; Eniu, A; Harvey, V; Hegg, R; Hickish, T; McNally, V; Ratnayake, J; Ross, G; Schneeweiss, A; Seo, JH; Tausch, C; Tsai, YF, 2013)		0.39
" Using bivariate analyses, we determined the association of abnormal CA125 (≥35 U/mL) with baseline GA, grades 3 to 5 toxicity (Common Terminology Criteria for Adverse Events version 3), dose adjustments, and hospitalization."( CA125 level association with chemotherapy toxicity and functional status in older women with ovarian cancer.
Feng, T; Gajra, A; Gross, CP; Hurria, A; Klepin, HD; Lichtman, SM; Mohile, S; Owusu, C; Tew, WP; Won, E, 2013)		0.39
" The most important dose-limiting side effect is hematologic toxicity."( Same Chemotherapy Regimen Leads to Different Myelotoxicity in Different Malignancies: A Comparison of Chemotherapy-Associated Myelotoxicity in Patients With Advanced Ovarian and Non-Small-Cell Lung Cancer.
Ciftci, R; Keskin, S; Kilic, L; Sen, F; Tas, F; Yildiz, I, )		0.13
" In this review, we have described the main characteristics of cisplatin, carboplatin, and oxaliplatin, focusing on their toxic effects and possible strategies to prevent them to improve the clinical outcomes in pediatric cancer patients."( Platinum compounds in children with cancer: toxicity and clinical management.
Arena, R; Ferrara, P; Pierri, F; Riccardi, R; Ruggiero, A; Scalzone, M; Triarico, S; Trombatore, G, 2013)		0.39
" Only eight cases of severe adverse events were observed in the study, which were deemed to be related to bevacizumab."( Safety and efficacy of first-line bevacizumab combination therapy in Chinese population with advanced non-squamous NSCLC: data of subgroup analyses from MO19390 (SAiL) study.
Bai, CX; Guan, ZZ; Jiang, GL; Shi, YK; Wang, MZ; Wu, YL; Zhang, YP; Zhou, CC; Zhu, YZ, 2014)		0.4
" Grade ≥3 adverse events typical of bevacizumab were no more common than in phase III bevacizumab ovarian cancer trials."( Efficacy and safety results from OCTAVIA, a single-arm phase II study evaluating front-line bevacizumab, carboplatin and weekly paclitaxel for ovarian cancer.
Freudensprung, U; Gladieff, L; Gonzalez-Martin, A; Gore, M; Kovalenko, N; Oaknin, A; Pignata, S; Ronco, JP; Scambia, G; Stroyakovsky, D; Tholander, B, 2013)		0.39
" Further, since carboplatin generates oxidative stress, polymorphisms of oxidative stress genes that regulate the cellular level of free radicals may have important roles in generating drug- related adverse effects."( GSTT1 null and MPO -463G>a polymorphisms and carboplatin toxicity in an Indian population.
Bag, A; Bag, N; Jeena, LM; Jyala, NS; Pant, NK, 2013)		0.39
" However, childhood cancer survivors (CCS) are at great risk for developing adverse effects caused by multimodal treatment for their malignancy."( Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer.
Blufpand, H; Bökenkamp, A; Jaspers, MW; Knijnenburg, SL; Kremer, LC; Mulder, RL; Schouten-Van Meeteren, AY; van Dulmen-den Broeder, E; Veening, MA, 2013)		0.39
" The full-text screening of the remaining 366 articles resulted in the inclusion of 57 studies investigating the prevalence of and sometimes also risk factors for early and late renal adverse effects of treatment for childhood cancer."( Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer.
Blufpand, H; Bökenkamp, A; Jaspers, MW; Knijnenburg, SL; Kremer, LC; Mulder, RL; Schouten-Van Meeteren, AY; van Dulmen-den Broeder, E; Veening, MA, 2013)		0.39
"The prevalence of renal adverse events after treatment with cisplatin, carboplatin, ifosfamide, radiation therapy involving the kidney region and/or nephrectomy ranged from 0% to 84%."( Early and late renal adverse effects after potentially nephrotoxic treatment for childhood cancer.
Blufpand, H; Bökenkamp, A; Jaspers, MW; Knijnenburg, SL; Kremer, LC; Mulder, RL; Schouten-Van Meeteren, AY; van Dulmen-den Broeder, E; Veening, MA, 2013)		0.39
"Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS."( Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness.
da Costa Miranda, V; da Silva Bessa, LR; da Silva, JR; de Freitas, D; de Paula Carvalho, J; de Souza Fêde, ÂB; Del Pilar Estevez Diz, M; Dos Anjos, CH; Filho, EA; Sanchez, FB, 2014)		0.4
"CD treatment seems to be a safe and effective chemotherapy regimen for platinum-sensitive recurrent epithelial ovarian cancer."( [Safety and efficacy of pegylated liposomal Doxorubicin and Carboplatin on platinum-sensitive recurrent epithelial ovarian cancer].
Aiko, K; Kamura, T; Kawano, R; Kurokawa, Y; Nasu, H; Nishio, S; Shimizu, T; Sumino, Y; Tachibana, T; Takemoto, S; Ushijima, K; Yokomine, M, 2013)		0.39
" Of the 460 cycles, adverse events, drug-related adverse events, and serious adverse events occurred in 179 (38."( Safety and efficacy of aprepitant, ramosetron, and dexamethasone for chemotherapy-induced nausea and vomiting in patients with ovarian cancer treated with paclitaxel/carboplatin.
Bae, DS; Choi, CH; Kim, BG; Kim, HJ; Kim, MK; Kim, TJ; Lee, JW; Lee, YY; Park, JY; Yoon, A, 2014)		0.4
" Hearing loss was graded using four scales (American Speech-Language-Hearing Association; Brock; Chang; and Common Terminology Criteria for Adverse Events, version 3 [CTCAEv3])."( Ototoxicity in children with high-risk neuroblastoma: prevalence, risk factors, and concordance of grading scales--a report from the Children's Oncology Group.
Bhatia, S; Chen, L; Gurney, JG; Kim, H; Knight, K; Kreissman, SG; Landier, W; Lee, J; London, WB; Schmidt, ML; Thomas, O; Wong, FL, 2014)		0.4
"Taurolidine infusion was safe in 6 healthy dogs and there were no significant side effects."( Pharmacokinetic study and evaluation of the safety of taurolidine for dogs with osteosarcoma.
Bracha, S; Brownlee, L; Helfand, SC; Marley, K; Mata, JE; Séguin, B; Simpson, J; Tracewell, WG, 2013)		0.39
" The primary endpoint was overall survival COS) and the secondary endpoint was adverse event (AE)."( Intraperitoneal chemotherapy for peritoneal carcinomatosis improves efficacy with acceptable safety: results of 200 cycles for 41 patients.
Huang, CQ; Li, G; Li, Y; Liu, Y; Yang, T, )		0.13
" Unfortunately, ototoxicity is a frequently encountered side effect of platinum-based chemotherapy."( Incidence of platinum-induced ototoxicity in pediatric patients in Quebec.
Alzahrani, M; Bezdjian, A; Carret, AS; Daniel, SJ; Emami, N; Gurberg, J; Peleva, E, 2014)		0.4
" The efficacy and adverse reactions after 2 cycles of chemotherapy were compared between these two groups."( Comparison of efficacy and safety between liposome-paclitaxel injection plus carboplatin and paclitaxel plus carboplatin as first line treatment in advanced non-small cell lung cancer.
Wang, HY; Zhang, XR, 2014)		0.4
"LPC group has the same efficacy with PC group and less adverse reactions than PC group."( Comparison of efficacy and safety between liposome-paclitaxel injection plus carboplatin and paclitaxel plus carboplatin as first line treatment in advanced non-small cell lung cancer.
Wang, HY; Zhang, XR, 2014)		0.4
"The severity of the toxic side effects of chemotherapy shows a great deal of interindividual variability, and much of this variation is likely genetically based."( Using Drosophila melanogaster to identify chemotherapy toxicity genes.
King, EG; Kislukhin, G; Long, AD; Walters, KN, 2014)		0.4
"The addition of bevacizumab to paclitaxel and carboplatin may provide an effective and safe treatment option for patients with advanced nonsquamous NSCLC with ILD."( The safety and efficacy of paclitaxel and carboplatin with or without bevacizumab for treating patients with advanced nonsquamous non-small cell lung cancer with interstitial lung disease.
Fujimoto, D; Katakami, N; Kato, R; Kawamura, T; Matsumoto, T; Nagata, K; Nakagawa, A; Otoshi, T; Otsuka, K; Shimizu, R; Tamai, K; Tomii, K, 2014)		0.4
"The anti-tumour effects and adverse events were evaluated in 163 MIBC patients who received systemic chemotherapy (SC, n = 34), intra-arterial chemotherapy (IAC, n = 50), or combined IAC and radiotherapy (IAC + R, n = 79)."( Efficacy and safety of systemic chemotherapy and intra-arterial chemotherapy with/without radiotherapy for bladder preservation or as neo-adjuvant therapy in patients with muscle-invasive bladder cancer: a single-centre study of 163 patients.
Hayashi, N; Matsuo, T; Miyata, Y; Nomata, K; Ohba, K; Sakai, H; Sakamoto, I; Uetani, M, 2015)		0.42
" The incidence of severe adverse events was higher in the IAC + R group (36."( Efficacy and safety of systemic chemotherapy and intra-arterial chemotherapy with/without radiotherapy for bladder preservation or as neo-adjuvant therapy in patients with muscle-invasive bladder cancer: a single-centre study of 163 patients.
Hayashi, N; Matsuo, T; Miyata, Y; Nomata, K; Ohba, K; Sakai, H; Sakamoto, I; Uetani, M, 2015)		0.42
" When further administration of carboplatin is precluded, oxaliplatin represents a safe and effective treatment strategy in the platinum-sensitive relapse setting."( Oxaliplatin is a safe alternative option for patients with recurrent gynecologic cancers after hypersensitivity reaction to Carboplatin.
Blum, BL; Frederick, PJ; Kolomeyevskaya, NV; Lele, SB; Miller, A; Odunsi, KO; Riebandt, GC, 2015)		0.42
" Spinal RT during the course of bevacizumab-based therapy was not associated with the occurrence of unexpected adverse effects."( Safety of spinal radiotherapy in metastatic cancer patients receiving bevacizumab therapy: a bi-institutional case series.
Annede, P; Bauduceau, O; Bosacki, C; Ceccaldi, B; Chargari, C; Dulou, R; Falk, AT; Ferrand, FR; Guy, JB; Helissey, C; Jacob, J; Langrand-Escure, J; Le Moulec, S; Magné, N; Mbagui, R; Mery, B; Vedrine, L, 2015)		0.42
" Four-thiouridylate, a promising antileukemic molecule with good therapeutic index, was by far the least toxic for CFU-GM of db/db mice."( Myelotoxicity of carboplatin is increased in vivo in db/db mice, the animal model of obesity-associated diabetes mellitus.
Aradi, J; Benkő, I; Géresi, K; Megyeri, A; Németh, J; Szabó, B; Szabó, Z, 2015)		0.42
"Four measures of the effectiveness of the microcapsules were evaluated: 1) release of carboplatin in response to radiation in vitro and in vivo; 2) detectability of their accumulation by computed tomography (CT) in vivo; 3) enhancement of antitumor effects in vivo; and 4) reduction of adverse effects in vivo."( Targeted concurrent chemoradiotherapy, by using improved microcapsules that release carboplatin in response to radiation, improves detectability by computed tomography as well as antitumor activity while reducing adverse effect in vivo.
Ehara, S; Goto, S; Harada, S; Ishii, K; Kamiya, T; Koka, M; Sato, T; Sera, K, 2015)		0.42
" A reduction in adverse effects was observed with the encapsulation of carboplatin, through localization of carboplatin around the tumor."( Targeted concurrent chemoradiotherapy, by using improved microcapsules that release carboplatin in response to radiation, improves detectability by computed tomography as well as antitumor activity while reducing adverse effect in vivo.
Ehara, S; Goto, S; Harada, S; Ishii, K; Kamiya, T; Koka, M; Sato, T; Sera, K, 2015)		0.42
" Importantly, unlike the free carboplatin, carboplatin in the form of PCL nanoparticles did not present any haemolytic activity in rat erythrocytes, a major side effect of this chemotherapeutic drug."( Poly (ɛ-caprolactone) nanoparticles of carboplatin: Preparation, characterization and in vitro cytotoxicity evaluation in U-87 MG cell lines.
Bhaskar, B; Chellan, V; Franklin, G; Karanam, V; Krishnamoorthy, B; Marslin, G; Natarajan, T; Siram, K, 2015)		0.42
"Docetaxel-cisplatin and 5-fluorouracil (TPF) chemotherapy (days 1-21) represents a standard but toxic regimen for advanced head and neck cancer (HNC)."( Feasibility and safety of dose-dense modified docetaxel-cisplatin or carboplatin and 5-fluorouracil regimen (mTPF) in locally advanced or metastatic head and neck cancers: a retrospective monocentric study.
Breheret, R; Capitain, O; Laccourreye, L; Linot, B; Peyraga, G; Yossi, S, 2015)		0.42
"Dose-dense mTPF (days 1-14) is safe and seems to be as effective as TPF (days 1-21)."( Feasibility and safety of dose-dense modified docetaxel-cisplatin or carboplatin and 5-fluorouracil regimen (mTPF) in locally advanced or metastatic head and neck cancers: a retrospective monocentric study.
Breheret, R; Capitain, O; Laccourreye, L; Linot, B; Peyraga, G; Yossi, S, 2015)		0.42
"Grade 3 or 4 neoadjuvant-related adverse events included fatigue (3 patients), neutropenia (3 patients), hypertension (1 patient)."( [Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma].
Ou, W; Xu, P; Yuan, C; Zhang, S, 2015)		0.42
"The treatment modality of neoadjuvant Bev-PC appears to be safe and tolerant in patients with stage IIIa lung adenocarcinoma."( [Safety of Neoadjuvant Bevacizumab plus Pemetrexed and Carboplatin 
in Patients with IIIa Lung Adenocarcinoma].
Ou, W; Xu, P; Yuan, C; Zhang, S, 2015)		0.42
" The most frequent adverse event of grade 3 or more was neutropenia (72%, 18/25)."( Efficacy and Safety of Combined Carboplatin, Paclitaxel, and Bevacizumab for Patients with Advanced Non-squamous Non-small Cell Lung Cancer with Pre-existing Interstitial Lung Disease: A Retrospective Multi-institutional Study.
Baba, T; Enomoto, Y; Goto, K; Kato, T; Kenmotsu, H; Murakami, H; Ogura, T; Takahashi, T; Watanabe, N; Yoh, K, 2015)		0.42
" The reasons for discontinuation were catheter-related problems (30%), disease progression (20%), or drug-related adverse effects (30%)."( Toxicity of intraperitoneal chemotherapy and risk factors for severe toxicity in optimally debulked ovarian cancer patients.
Koo, YJ; Lim, KT, 2015)		0.42
"Despite the high rate of adverse events, IP chemotherapy can be delivered with a high completion rate and manageable toxicity to patients with optimally debulked ovarian cancer."( Toxicity of intraperitoneal chemotherapy and risk factors for severe toxicity in optimally debulked ovarian cancer patients.
Koo, YJ; Lim, KT, 2015)		0.42
" After combination chemotherapy, genotype analysis was conducted, and toxic effects were evaluated according to the Common Toxicity Criteria."( Genetic variation of CYP3A5 influences paclitaxel/carboplatin-induced toxicity in Chinese epithelial ovarian cancer patients.
Cheng, L; Guo, Y; Hu, L; Lv, QL; Qin, CZ; Wu, NY; Zhou, HH, 2016)		0.43
" They continued with olaparib monotherapy in their best interest if they failed to tolerate the combination due to the treatment-related adverse events (TRAEs)."( Long-term safety and anti-tumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer.
Beijnen, JH; Harms, E; Marchetti, S; Mergui-Roelvink, MW; Rehorst, H; Schellens, JH; Sonke, GS; Steeghs, N; van der Noll, R, 2015)		0.42
"Continued long-term daily olaparib was found to be safe and tolerable."( Long-term safety and anti-tumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer.
Beijnen, JH; Harms, E; Marchetti, S; Mergui-Roelvink, MW; Rehorst, H; Schellens, JH; Sonke, GS; Steeghs, N; van der Noll, R, 2015)		0.42
" The frequency and severity of adverse events were consistent with previous analyses; no new safety concerns were identified."( Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer.
Aghajanian, C; Blank, SV; Goff, B; Husain, A; Nycum, LR; Wang, YV, 2015)		0.42
"Severe toxicity and interruption of radiotherapy were more frequent in patients with multiple adverse predictive factors."( Predictive factors for survival and correlation to toxicity in advanced Stage III non-small cell lung cancer patients with concurrent chemoradiation.
Ahn, SJ; Ban, HJ; Chung, WK; Jeong, JU; Kim, KS; Kim, YC; Kim, YH; Nam, TK; Oh, IJ; Song, JY; Yoon, MS, 2016)		0.43
"Carboplatin-etoposide combination therapy for NEC may have comparable effectiveness and milder adverse events than cisplatin-etoposide combination therapy."( Efficacy and Safety of Carboplatin and Etoposide Combination Chemotherapy for Extrapulmonary Neuroendocrine Carcinoma: A Retrospective Case Series.
Imai, H; Ishioka, C; Komine, K; Okita, A; Saijo, K; Shimodaira, H; Shirota, H; Takahashi, M; Takahashi, S, 2016)		0.43
" Farletuzumab/carboplatin/pegylated liposomal doxorubicin was generally well tolerated, with no farletuzumab-related grades 3-4 adverse events."( Phase 1b safety study of farletuzumab, carboplatin and pegylated liposomal doxorubicin in patients with platinum-sensitive epithelial ovarian cancer.
Alvarez, RD; Armstrong, DK; Jelovac, D; Kim, KH; Schwartz, B; Schweizer, C; Weil, SC, 2016)		0.43
" We, therefore, investigated the cellular toxic effects of melphalan, topotecan and carboplatin on the RPE in a cell culture model."( Toxic effects of melphalan, topotecan and carboplatin on retinal pigment epithelial cells.
Aisenbrey, S; Hagemann, U; Januschowski, K; Schnichels, S; Schrader, M; Süsskind, D, 2016)		0.43
"Morphological monitoring and toxicity assays indicate a direct toxic effect of melphalan and the other two cytostatic drugs on ARPE19 cells."( Toxic effects of melphalan, topotecan and carboplatin on retinal pigment epithelial cells.
Aisenbrey, S; Hagemann, U; Januschowski, K; Schnichels, S; Schrader, M; Süsskind, D, 2016)		0.43
" The most common adverse events were those associated with chemotherapy."( A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse.
Armstrong, D; Bamias, A; Fujiwara, K; Gorbunova, V; Herzog, TJ; O'Shannessy, D; Ochiai, K; Poole, C; Scambia, G; Schweizer, C; Sehouli, J; Teneriello, M; Vergote, I; Wang, W; Weil, SC, 2016)		0.43
" Grade 3-4 adverse events included leukopenia (2/39), and neutropenia (3/39) in first-line therapy versus neutropenia (1/40) and thrombocytopenia (2/40) in second-line treatment."( A retrospective analysis of efficacy and safety of adding bevacizumab to chemotherapy as first- and second-line therapy in advanced non-small-cell lung cancer (NSCLC).
Chen, N; Fang, W; Hu, Z; Huang, J; Quan, R; Zhan, J; Zhang, H; Zhang, L; Zhou, T, 2016)		0.43
" However, no increase in recorded adverse events was observed, suggesting that the clinical relevance in toxicity from higher doses was minimal."( Impact of Isotope Dilution Mass Spectrometry (IDMS) Standardization on Carboplatin Dose and Adverse Events.
Donald Harvey, R; Lawson, J; McKibbin, T; Switchenko, JM, 2016)		0.43
" For them, we performed a pilot study to evaluate the feasibility of chemotherapy with carboplatin and S-1, which are known as cytotoxic drug with rare development of ILD as adverse event."( Safety and efficacy of S-1 in combination with carboplatin in non-small cell lung cancer patients with interstitial lung disease: a pilot study.
Baba, T; Hagiwara, E; Ikeda, S; Iwasawa, T; Kato, T; Komatsu, S; Ogura, T; Okuda, R; Satoh, H; Sekine, A; Shinohara, T, 2016)		0.43
" The aim of this study was to identify the risk factors for the early serious adverse events (SAEs) (during cycles 1-2) in elderly receiving platinum-based chemotherapy, and to explore the clinical characteristics of patients who require early treatment termination without progressive disease (PD)."( Can we predict the development of serious adverse events (SAEs) and early treatment termination in elderly non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy?
Ando, M; Hase, T; Hasegawa, Y; Kato, T; Kojima, E; Kondo, M; Matsumoto, M; Morise, M; Nozaki, Y; Ogasawara, T; Ogawa, M; Saito, H; Shindoh, J; Sugino, Y; Suzuki, R, 2016)		0.43
"5 %), followed by grade 2 non-hematological adverse events (AEs) (3 %)."( Can we predict the development of serious adverse events (SAEs) and early treatment termination in elderly non-small cell lung cancer (NSCLC) patients receiving platinum-based chemotherapy?
Ando, M; Hase, T; Hasegawa, Y; Kato, T; Kojima, E; Kondo, M; Matsumoto, M; Morise, M; Nozaki, Y; Ogasawara, T; Ogawa, M; Saito, H; Shindoh, J; Sugino, Y; Suzuki, R, 2016)		0.43
" Unfortunately, ototoxicity is a frequently encountered side effect of platinum-based chemotherapy."( Platinum-induced ototoxicity: a review of prevailing ototoxicity criteria.
Daniel, SJ; Peleva, E; Waissbluth, S, 2017)		0.46
" Grade 2 or worse adverse events were found during treatment in 309 (94%) of 327 patients in the chemoradiotherapy group versus 145 (44%) of 326 patients in the radiotherapy alone group, and grade 3 or worse events were found in 198 (61%) of 327 patients in the chemoradiotherapy group versus 42 (13%) of 326 patients in the radiotherapy alone group (p<0·0001), with most of the grade 3 adverse events being haematological (45%)."( Toxicity and quality of life after adjuvant chemoradiotherapy versus radiotherapy alone for women with high-risk endometrial cancer (PORTEC-3): an open-label, multicentre, randomised, phase 3 trial.
Baron, MH; Bessette, P; Colombo, A; Creutzberg, CL; de Boer, SM; Fyles, A; Haie-Meder, C; Katsaros, D; Khaw, P; Kitchener, HC; Kruitwagen, RF; Ledermann, JA; Mileshkin, L; Nijman, HW; Nout, RA; Ottevanger, PB; Powell, ME; Putter, H; Smit, VT; Verhoeven-Adema, KW, 2016)		0.43
" Our results would aid clinicians to make decisions of coadministration drugs to avoid drug interaction-induced side effects for achievement of safe and appropriate chemotherapy with pemetrexed."( Lansoprazole Exacerbates Pemetrexed-Mediated Hematologic Toxicity by Competitive Inhibition of Renal Basolateral Human Organic Anion Transporter 3.
Enokiya, T; Fujimoto, H; Hamada, Y; Ikemura, K; Iwamoto, T; Kaya, C; Kobayashi, T; Muraki, Y; Nakahara, H; Okuda, M, 2016)		0.43
" ERCC2 Asp312Asn G-alelle, ABCB1 C1236T-TT and the IL1B rs12621220-CT/TT genotypes conferred a higher risk to present multiple adverse events."( Pharmacogenetic predictors of toxicity to platinum based chemotherapy in non-small cell lung cancer patients.
Alnatsha, A; Calleja-Hernández, MŸ; Cañadas-Garre, M; Delgado, JR; Faus-Dáder, MJ; Pérez-Ramírez, C; Villar, E, 2016)		0.43
" Four important transporter genes are expressed in the kidney, including organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), ATP-binding cassette subfamily B member 1 (ABCB1), and ATP-binding cassette subfamily C member 2 (ABCC2), and genetic polymorphisms in these genes may alter the efficacy and adverse effects of platinum drugs."( Associations of genetic polymorphisms of the transporters organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), and ATP-binding cassette subfamily C member 2 (ABCC2) with platinum-based chemotherapy response and toxicity in non-sma
Chen, J; Liu, JY; Liu, ZQ; Qian, CY; Wang, Y; Yin, JY; Zheng, Y; Zhou, HH, 2016)		0.43
" The most common all-grade adverse events were hypertension (55% of patients), neutropenia (49%), and alopecia (43%)."( Efficacy and Safety of Bevacizumab-Containing Therapy in Newly Diagnosed Ovarian Cancer: ROSiA Single-Arm Phase 3B Study.
Bamias, A; Chmielowska, E; Colombo, N; Davidenko, I; DeCensi, A; Gadducci, A; González-Martín, A; Hegg, R; Joly, F; Korach, J; Martin, N; Mendiola, C; Oza, AM; Pautier, P; Robb, S; Selle, F; Zamagni, C; Zvirbule, Z, 2017)		0.46
" Select adverse events (those with a potential immunologic cause) of any grade were observed in six, four, six, and five patients in arms A, B, C, and D, respectively."( Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study.
Fujiwara, Y; Goto, K; Horinouchi, H; Hozumi, H; Kanda, S; Kitazono, S; Kubo, E; Mizugaki, H; Nokihara, H; Shiraishi, H; Sunami, K; Tamura, T; Tanaka, A; Utsumi, H; Yamamoto, N, 2016)		0.43
"In order to clarify the risk of hematotoxicity of carboplatin, we inspected 19901 case reports of non-small cell lung cancer patients that were submitted to the FDA Adverse Event Reporting System (FAERS) between January 2004 and December 2015."( Carboplatin-induced hematotoxicity among patients with non-small cell lung cancer: Analysis on clinical adverse events and drug-gene interactions.
Cheng, ML; Cheng, YJ; Du, J; Hu, XW; Hu, YX; Huang, NW; Liu, HJ; Long, QZ; Wan, F; Wu, R; Yao, YM; Yu, L; Zhao, XK; Zhu, JJ; Zhu, LL, 2017)		0.46
" A higher incidence of some adverse events was observed with onartuzumab versus placebo, including peripheral edema (30% vs."( Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non-Small-Cell Lung Cancer.
Boyer, M; Braiteh, F; Cosgriff, T; De Braud, F; Hsu, J; Kaen, D; Kingsley, CD; Lawler, W; Lena, H; Lowe, T; Mekhail, T; Novello, S; Phan, S; Schütte, W; Wakelee, H; Zvirbule, Z, 2017)		0.46
" The adverse events were generally manageable and no treatment-related deaths occurred."( [Outcomes and Toxicity of Concurrent Radiotherapy with Carboplatin/Paclitaxel 
Administrated Every Three Weeks in Inoperable Advanced 
Non-small Cell Lung Cancer: 
A Retrospective Study from A Single Center].
Hu, K; Huang, X; Si, X; Wang, H; Wang, M; Xu, Y; Zhang, L; Zhang, X; Zhao, J; Zhong, W, 2016)		0.43
" A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented."( Efficacy and safety of bevacizumab-containing neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: Results from the ANTHALYA trial.
Chereau, E; Colombo, PE; Cottu, P; Dupin, J; Fauvet, R; Floquet, A; Follana, P; Fourchotte, V; Ghazi, Y; Gouy, S; Joly, F; Kalbacher, E; Lambaudie, E; Lecuru, F; Lesoin, A; Martin-Francoise, S; Pomel, C; Rouzier, R; Selle, F; Zohar, S, 2017)		0.46
" Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP."( Efficacy and safety of bevacizumab-containing neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: Results from the ANTHALYA trial.
Chereau, E; Colombo, PE; Cottu, P; Dupin, J; Fauvet, R; Floquet, A; Follana, P; Fourchotte, V; Ghazi, Y; Gouy, S; Joly, F; Kalbacher, E; Lambaudie, E; Lecuru, F; Lesoin, A; Martin-Francoise, S; Pomel, C; Rouzier, R; Selle, F; Zohar, S, 2017)		0.46
" Understanding these mechanisms is important as neurotoxicity is the predominant side-effect of platinum-based chemotherapy."( Neurotoxicity Associated with Platinum-Based Anti-Cancer Agents: What are the Implications of Copper Transporters?
McQuade, R; Nurgali, K; Rybalka, E; Stojanovska, V, 2017)		0.46
" Nausea and vomiting occurred as adverse event (AE) in eight out of 25 treatments (32%), with seven of eight events (87."( Degradable Starch Microspheres Transcatheter Arterial Chemoembolization (DSM-TACE) in Intrahepatic Cholangiocellular Carcinoma (ICC): Results from a National Multi-Center Study on Safety and Efficacy.
Albrecht, T; Michalik, K; Nolte-Ernsting, C; Pereira, PL; Pützler, M; Schicho, A; Stroszczynski, C; Wiggermann, P, 2017)		0.46
"Combined carboplatin and VP16P may be compatible for intravitreal injection therapy, and a single dose of 2 µg/25 µg appears to be safe in a rabbit model."( Preclinical Acute Ocular Safety Study of Combined Intravitreal Carboplatin and Etoposide Phosphate for Retinoblastoma.
Elner, VM; Harbour, JW; Mohney, BG; Musch, DC; Smith, AB; Smith, BD; Smith, SJ, 2017)		0.46
" Patient characteristics and incidence of adverse events (AEs) were described for each cohort."( Safety profiles of non-small cell lung cancer patients treated with pemetrexed plus carboplatin: a real-world retrospective, observational, cohort study.
Chen, J; Chen, L; Goodloe, RJ; John, WJ; San Antonio, B; Yan, Y, 2017)		0.46
"This meta-analysis compared safety profiles (selected drug-related treatment-emergent adverse events [TEAEs]) of first-line pemetrexed plus carboplatin (PCb) area under the concentration-time curve 5 mg/min•mL (PCb5) or 6 mg/min•mL (PCb6), two widely used regimens in clinical practice for advanced non-squamous non-small cell lung cancer."( Meta-analysis of pemetrexed plus carboplatin doublet safety profile in first-line non-squamous non-small cell lung cancer studies.
Chen, J; John, WJ; Liu, J; Okamoto, I; Rodrigues-Pereira, J; San Antonio, B; Schuette, WH; Stinchcombe, TE; Zinner, RG, 2017)		0.46
" However, there have also been adverse side effects such as ototoxic hearing loss because of chemotherapy."( Parents are aware of the ototoxic effects of chemotherapy in paediatrics undergoing cancer treatment - Professional versus parental views: A pilot study.
Hughes, K; Moroe, NF, 2017)		0.46
"Our results confirm that GP has an adverse impact on the renal function of patients with UUT-UC who retain a solitary kidney, but it can be safely administered to the majority of these patients without inducing SNT."( The renal safety and efficacy of combined gemcitabine plus cisplatin and gemcitabine plus carboplatin chemotherapy in Chinese patients with a solitary kidney after nephroureterectomy.
An, X; Deng, YF; Jiang, WQ; Li, LR; Shao, C; Shi, YX; Sun, P; Thomas, R; Xue, C; Yang, W, 2017)		0.46
" Thirty-three (66%) patients completed the chemotherapy course, while the treatment was delayed or discontinued in the other 17 (34%) patients because of adverse events (AEs)."( Neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin administered every 3 weeks for Japanese women with HER2-positive primary breast cancer: efficacy and safety.
Fujiuchi, N; Hasebe, T; Hirokawa, E; Matsuura, K; Misumi, M; Osaki, A; Saeki, T; Sakurai, T; Shigekawa, T; Shimada, H; Sugitani, I; Takahashi, T; Takeuchi, H; Ueda, S, 2017)		0.46
"2% of patients discontinuing one or both drugs because of adverse events (AEs)."( Antitumor activity and safety profile of weekly carboplatin plus paclitaxel in metastatic breast cancer: a ten-year, monocentric, retrospective study.
Bianchi, G; Capri, G; de Braud, F; Ferrari, B; Maggi, C; Mariani, G; Mennitto, A; Mennitto, R; Milano, M; Re, B; Rinaldi, L; Stefanetti, C; Vernieri, C, 2017)		0.46
" Among propensity score-matched patients, we found no difference between regimens in health care use overall or for chemotherapy-related adverse events (ACTH, 34% v TCH, 36."( Comparative Toxicity and Effectiveness of Trastuzumab-Based Chemotherapy Regimens in Older Women With Early-Stage Breast Cancer.
Carey, LA; Dusetzina, SB; Hinton, SP; Meng, K; Meyer, AM; Reeder-Hayes, KE, 2017)		0.46
" Grade 4 hematologic toxicity and ≥Grade 3 non-hematologic toxicity both occurred in 8% of the patients, but no patient discontinued NAC because of adverse events."( Efficacy and safety of dose-dense paclitaxel plus carboplatin as neoadjuvant chemotherapy for advanced ovarian, fallopian tube or peritoneal cancer.
Aoki, D; Hashimoto, S; Hirano, T; Hirasawa, A; Iwasa, N; Kataoka, F; Makabe, T; Nanki, Y; Nomura, H; Sakai, K; Yamagami, W; Yoshihama, T, 2017)		0.46
"All 66 treated patients experienced at least one adverse event (AE)."( A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non-s
Adjei, AA; Bahleda, R; Besse, B; Dy, GK; Ferte, C; Groen, HJM; Lin, W; Morrissey, K; Planchard, D; Schutzman, JL; Shankar, G; Soria, JC; Ware, J; Zhou, J, 2017)		0.46
" Therefore, to gain more information and to validate the safety of using generic paclitaxel NK in a tri-weekly regimen, we investigated the incidences of adverse events in response to it in a larger number of patients."( [Safety Evaluation of Paclitaxel Injection NK in Tri-Weekly Administration of Paclitaxel plus Carboplatin(TC Therapy) for Gynecological Cancers].
Ikeda, T; Kisu, I; Sakamoto, Y, 2017)		0.46
"The TCH protocol is an efficacious neoadjuvant chemotherapy regimen for locally advanced and oligometastatic breast cancer and is safe and well tolerated in this population."( Retrospective study of efficacy and safety of neoadjuvant docetaxel, carboplatin, and trastuzumab in HER2-positive locally advanced and oligometastatic breast cancer: An Indian experience.
Deo, S; Gogia, A; Mathur, S; Sharma, DN; Shukla, NK; Tiwari, A, )		0.13
" Secondary: To describe the demographic and clinical characteristics of the study sample, as well as the adverse effects and survival."( Toxicity of docetaxel, carboplatin, and trastuzumab combination as adjuvant or neo-adjuvant treatment for Her2 positive breast cancer patients and impact of colony-stimulating factor prophylaxis.
Aviñó, V; Bayo, J; Jiménez, F; Toscano, F, 2018)		0.48
"BACKGROUND The aim of this study was to compare nutrition-related adverse events and clinical outcomes of ifosfamide, carboplatin, and etoposide regimen (ICE therapy) and ranimustine, carboplatin, etoposide, and cyclophosphamide regimen (MCEC therapy) instituted as pretreatment for autologous peripheral blood stem cell transplantation."( Comparison of Nutrition-Related Adverse Events and Clinical Outcomes Between ICE (Ifosfamide, Carboplatin, and Etoposide) and MCEC (Ranimustine, Carboplatin, Etoposide, and Cyclophosphamide) Therapies as Pretreatment for Autologous Peripheral Blood Stem C
Aoyama, T; Arai, H; Ikeda, T; Imataki, O; Ishide, K; Katsumata, N; Kume, T; Mori, M; Shiozaki, H, 2018)		0.48
" Conclusion Combination chemotherapy of nab-PTX and carboplatin may be an effective and safe treatment option for patients with inoperable lung SCC with IIPs."( The Safety and Efficacy of Treatment with Nab-paclitaxel and Carboplatin for Patients with Advanced Squamous Non-small Cell Lung Cancer Concurrent with Idiopathic Interstitial Pneumonias.
Amano, H; Fujita, T; Hayama, N; Hirano, S; Hiroishi, T; Nakamura, M; Nakamura, S; Shikano, K; Tabeta, H; Yanagisawa, A, 2018)		0.48
"Results suggest that oral NEPA is effective and safe in preventing CINV in patients with gynecological cancers treated with cisplatin- or carboplatin-based CT."( Efficacy and Safety of Oral NEPA (Netupitant/Palonosetron), the First Fixed-Combination Antiemetic, in Patients With Gynecological Cancers Receiving Platinum-Based Chemotherapy.
Borroni, ME; Bošnjak, SM; Jordan, K; Rizzi, G; Stamatovic, L, 2018)		0.48
"Sensorineural hearing loss is a potential side effect of platinum-based chemotherapy."( Incidence and associated risk factors for platinum-induced ototoxicity in pediatric patients.
Becker, A; Chuang, A; Del Valle, Á; Waissbluth, S, 2018)		0.48
" Despite the fact that CV therapy is widely used for pediatric patients with LGG, no study has reported detailed neurological adverse events and outcome with this treatment regimen."( Carboplatin and vincristine neurotoxicity in the treatment of pediatric low-grade gliomas.
Delisle, JF; Perreault, S; Robert-Boire, V; Rosca, L; Samson, Y, 2018)		0.48
" Regarding bevacizumab-specific adverse events ≥ grade 3, incidence rates of thromboembolic events (1."( Bevacizumab combined with platinum-taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial).
Arakawa, A; Asai-Sato, M; Hongo, A; Inokuchi, Y; Kamiura, S; Kato, K; Komiyama, S; Matsumoto, T; Sugiyama, T; Tabata, T; Takano, H; Takeshima, N, 2019)		0.51
" Adverse events, tumor response, and progression-free survival (PFS) were determined."( Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer.
Birrer, MJ; Gonzalez-Martin, A; Malek, K; Martin, LP; Moore, KN; O'Malley, DM; Vergote, I, 2018)		0.48
" Adverse events were generally mild (≤ grade 2) with nausea, diarrhea, thrombocytopenia, blurred vision, and fatigue being the most common treatment-emergent toxicities."( Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer.
Birrer, MJ; Gonzalez-Martin, A; Malek, K; Martin, LP; Moore, KN; O'Malley, DM; Vergote, I, 2018)		0.48
" Secondary endpoints were the NAC response rate, adverse events during NAC, and perioperative complications."( Safety and efficacy of neoadjuvant chemotherapy containing bevacizumab and interval debulking surgery for advanced epithelial ovarian cancer: A feasibility study.
Komiyama, S; Kubushiro, K; Kugimiya, T, 2018)		0.48
" Adverse events ≥ grade 3 during NAC were neutropenia (78."( Safety and efficacy of neoadjuvant chemotherapy containing bevacizumab and interval debulking surgery for advanced epithelial ovarian cancer: A feasibility study.
Komiyama, S; Kubushiro, K; Kugimiya, T, 2018)		0.48
"CBDCA/nab-PTX combination chemotherapy was safe for elderly patients and those with ILD."( [Efficacy and Safety of Carboplatin/Nanoparticle Albumin-Bound Paclitaxel Combination Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer or Recurrent Non-Small-Cell Lung Cancer Following Surgery].
Ishimoto, H; Mukae, H; Noguchi, S; Shimabukuro, I; Tanaka, F; Torii, R; Uyama, K; Yatera, K; Yoshii, C, 2018)		0.48
"Platinum drugs, including carboplatin and oxaliplatin, are commonly used chemotherapy drugs that kill cancer cells by forming toxic drug-DNA adducts."( Correlation of Platinum Cytotoxicity to Drug-DNA Adduct Levels in a Breast Cancer Cell Line Panel.
de Vere White, R; Henderson, PT; Malfatti, MA; Pan, CX; Scharadin, TM; Turteltaub, KW; Wang, S; Zimmermann, M, 2018)		0.48
"Carboplatin IP and weekly IV paclitaxel was well-tolerated with a side-effect profile similar to or better than previously published traditional treatment regimens."( Treatment Tolerance and Side Effects of Intraperitoneal Carboplatin and Dose-Dense Intravenous Paclitaxel in Ovarian Cancer.
Bertrand, M; Bisch, SP; Gawlik, C; McGee, J; Prefontaine, M; Sugimoto, A; Welch, S, 2018)		0.48
" Some studies have suggested that concomitant drugs may be the risk factors for severe adverse events."( Effects of proton pump inhibitors on severe haematotoxicity induced after first course of pemetrexed/carboplatin combination chemotherapy.
Araki, R; Hamamoto, T; Keira, T; Masuda, Y; Tanaka, T; Yamada, H, 2019)		0.51
"Carboplatin AUC10 is a safe and effective treatment for stage II/III seminoma with better health-related quality of life than experienced with combination cisplatin-based chemotherapy."( A Qualitative Analysis of the Impact of Carboplatin AUC 10 on Physical, Work Functioning and Bone Marrow Toxicity Among Seminoma Patients - A Single-centre Experience.
Gogbashian, A; Hall, M; Hawkins, A; Milic, M; Rustin, G; Sharma, A, )		0.13
" For non-hematological adverse events, grade ≥3 sensory neuropathy and arthralgia occurred more frequently in the control arm than in the experimental arm."( Efficacy and safety of nanoparticle albumin-bound paclitaxel in non-small cell lung cancer: a systematic review and meta-analysis.
Hu, J; Liu, S; Tan, H, 2019)		0.51
" In this study, we evaluated the role of three SNPs in predicting the onset of adverse events for lung cancer patients receiving cisplatin or carboplatin in adjuvant, neo-adjuvant and metastatic settings."( ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study.
Cattaneo, MT; Cheli, S; Clementi, E; Dalu, D; De Francesco, D; De Troia, B; Falvella, FS; Fasola, C; Ferrario, S; Filipazzi, V; Gambaro, AR; Isabella, L; Somma, L; Tosca, N, 2019)		0.51
" Patient characteristics and genotypes were correlated with hematological, gastrointestinal and renal toxicity as recorded by Common Terminology Criteria for Adverse Event (CTCAE) v4."( ABCB1 c.3435C>T polymorphism is associated with platinum toxicity: a preliminary study.
Cattaneo, MT; Cheli, S; Clementi, E; Dalu, D; De Francesco, D; De Troia, B; Falvella, FS; Fasola, C; Ferrario, S; Filipazzi, V; Gambaro, AR; Isabella, L; Somma, L; Tosca, N, 2019)		0.51
"Dermatological adverse events have frequently been reported after immune checkpoint inhibition."( Cutaneous Toxicity After Chemoradiotherapy and PD-L1 Inhibition in Two Patients with Esophageal Adenocarcinoma: More than Meets the Eye.
Ambarus, CA; Menting, SP; van den Ende, T; van Laarhoven, HWM; van Oijen, MGH, 2019)		0.51
"To evaluate hematologic adverse effect profiles associated with frontline platinum-based chemotherapy in ovarian cancer patients according to BRCA 1/2 mutational status."( Is BRCA mutational status a predictor of platinum-based chemotherapy related hematologic toxicity in high-grade serous ovarian cancer patients?
Benedetti Panici, P; Boccia, SM; Di Donato, V; Di Mauro, F; Giancotti, A; Musacchio, L; Muzii, L; Palaia, I; Perniola, G; Tomao, F, 2019)		0.51
" Hematologic toxicity profiles of BRCA mutated patients were compared to non-mutated patients, according to EORTC Common Terminology Criteria for Adverse Events (CTCAE_4."( Is BRCA mutational status a predictor of platinum-based chemotherapy related hematologic toxicity in high-grade serous ovarian cancer patients?
Benedetti Panici, P; Boccia, SM; Di Donato, V; Di Mauro, F; Giancotti, A; Musacchio, L; Muzii, L; Palaia, I; Perniola, G; Tomao, F, 2019)		0.51
" Finally, the total number of hematologic adverse events compared between the two groups of patients during the entire treatment period showed a substantial higher rate of hematologic adverse events in BRCA mutated population."( Is BRCA mutational status a predictor of platinum-based chemotherapy related hematologic toxicity in high-grade serous ovarian cancer patients?
Benedetti Panici, P; Boccia, SM; Di Donato, V; Di Mauro, F; Giancotti, A; Musacchio, L; Muzii, L; Palaia, I; Perniola, G; Tomao, F, 2019)		0.51
"To evaluate adverse events and outcomes in dogs with appendicular osteosarcoma treated with limb amputation followed by a single SC infusion of carboplatin."( Adverse events and outcomes in dogs with appendicular osteosarcoma treated with limb amputation and a single subcutaneous infusion of carboplatin.
Kuntz, CA; Santamaria, AC; Simcock, JO, 2019)		0.51
"Medical records were reviewed, and data collected included signalment, tumor location, treatment, results of clinicopathologic analyses and diagnostic imaging, adverse effects of chemotherapy, metastasis-free interval, survival time, and communications with owners and referring veterinarians."( Adverse events and outcomes in dogs with appendicular osteosarcoma treated with limb amputation and a single subcutaneous infusion of carboplatin.
Kuntz, CA; Santamaria, AC; Simcock, JO, 2019)		0.51
" Prostate-specific antigen (PSA) responses (> 50% decline of PSA from baseline), progression-free survival, overall survival, and adverse events were examined."( Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer.
Akamatsu, S; Fujiwara, M; Goto, T; Inoue, T; Kobayashi, T; Mizuno, K; Ogawa, O; Saito, R; Sawada, A; Segawa, T; Sumiyoshi, T; Yamasaki, T; Yoshino, T, 2019)		0.51
" The adverse event profile was favorable."( Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer.
Akamatsu, S; Fujiwara, M; Goto, T; Inoue, T; Kobayashi, T; Mizuno, K; Ogawa, O; Saito, R; Sawada, A; Segawa, T; Sumiyoshi, T; Yamasaki, T; Yoshino, T, 2019)		0.51
"Platinum-based chemotherapy often fails due to its severe adverse effects."( Adverse Effects Profile of Dicycloplatin (DCP) Offers Chemotherapeutic Advantage Over Cisplatin and Carboplatin.
Cecil, C; Crigger, C; Guo, YI; Hogan, T; Jiang, BH; Jiao, S; Liang, X; Morley, C; Salkini, MW; Washington, IM; Williams, DJ; Winn, AC; Yan, B; Yang, X; Yu, JJ; Zheng, J, 2019)		0.51
" Experimental studies showed that dicycloplatin is less toxic to bone marrow and spleen of mice than cisplatin and carboplatin."( Adverse Effects Profile of Dicycloplatin (DCP) Offers Chemotherapeutic Advantage Over Cisplatin and Carboplatin.
Cecil, C; Crigger, C; Guo, YI; Hogan, T; Jiang, BH; Jiao, S; Liang, X; Morley, C; Salkini, MW; Washington, IM; Williams, DJ; Winn, AC; Yan, B; Yang, X; Yu, JJ; Zheng, J, 2019)		0.51
" We retrieved evidence on treatment-related grade III/IV adverse events, progression-free survival (PFS) and overall survival (OS)."( A systematic literature review and network meta-analysis of effectiveness and safety outcomes in advanced melanoma.
Franken, MG; Gheorghe, M; Haanen, JBAG; Leeneman, B; Uyl-de Groot, CA; van Baal, PHM, 2019)		0.51
" The primary endpoints were chemotherapy-related adverse events (AEs), including treatment-related hospitalization or death."( Comparative Study of the Safety and Efficacy of First-Line Cisplatin and Carboplatin Chemotherapy in Elderly Patients with Metastatic Urothelial Carcinoma.
Chiang, PH; Hsieh, MC; Huang, CC; Huang, CH; Huang, SY; Liu, JM; Luo, HL; Rau, KM; Su, HY; Sung, MT; Wu, CC, 2020)		0.56
" Alopecia was the most predominant side effect for BC patients, whereas OC patients were highly afflicted by numbness in limbs."( Perception of side effects associated with anticancer treatment in women with breast or ovarian cancer (KEM-GO-1): a prospective trial.
Ataseven, B; Bluni, V; Bommert, M; Breit, E; du Bois, A; Frindte, J; Gebers, G; Harter, P; Heitz, F; Kostara, A; Kuemmel, S; Prader, S; Reinisch, M; Schneider, S; Traut, A; Vogt, C, 2020)		0.56
" Current treatments have many adverse effects."( Low retinal toxicity of intravitreal carboplatin associated with good retinal tumour control in transgenic murine retinoblastoma.
Cassoux, N; Doz, F; Fréneaux, P; Leboucher, S; Lemaître, S; Poyer, F; Thomas, CD, 2020)		0.56
" Newer generations of drugs are developed to replace parent drugs, with the potential benefits of less toxic side effects."( Comparative gonadotoxicity of the chemotherapy drugs cisplatin and carboplatin on prepubertal mouse gonads.
Allen, CM; Lopes, F; Mitchell, RT; Spears, N, 2020)		0.56
" We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit-risk profile of this regimen."( Safety and patient-reported outcomes of atezolizumab, carboplatin, and etoposide in extensive-stage small-cell lung cancer (IMpower133): a randomized phase I/III trial.
Andric, Z; Atagi, S; Califano, R; De Boer, R; Garassino, M; Horn, L; Kabbinavar, F; Karaseva, N; Każarnowicz, A; Lam, S; Lee, JS; Liu, SV; Mansfield, AS; Morris, S; Quach, C; Reck, M; Sánchez, A; Wen, X; Yu, W, 2020)		0.56
" Their efficiency is hampered by serious toxic effects against healthy tissues as well."( The expression of copper transporters associated with the ototoxicity induced by platinum-based chemotherapeutic agents.
Brie, I; Cenariu, M; Fischer-Fodor, E; Gurzau, E; Maniu, A; Perde-Schrepler, M; Pop, C; Valcan, A; Virag, P, 2020)		0.56
"Neoadjuvant radiotherapy with 46 Gy and concomitant chemotherapy with paclitaxel and carboplatin for the treatment of locally advanced esophageal carcinoma is safe and effective."( Modification of preoperative radiochemotherapy for esophageal cancer (CROSS protocol) is safe and efficient with no impact on surgical morbidity.
Asari, R; Beer, A; Ilhan-Mutlu, A; Jomrich, G; Kristo, I; Paireder, M; Preusser, M; Rieder, E; Schmid, R; Schoppmann, SF, 2020)		0.56
" No unexpected severe adverse events or treatment-related deaths occurred."( Five-year safety and efficacy data from a phase Ib study of nivolumab and chemotherapy in advanced non-small-cell lung cancer.
Fujiwara, Y; Goto, Y; Horinouchi, H; Kanda, S; Nokihara, H; Ohe, Y; Tamura, T; Yamamoto, N; Yamamoto, T, 2020)		0.56
" The incidence, nature, and severity of adverse events (AEs) were assessed."( Safety and Patient-Reported Outcomes of Atezolizumab Plus Chemotherapy With or Without Bevacizumab Versus Bevacizumab Plus Chemotherapy in Non-Small-Cell Lung Cancer.
Barone, C; Coleman, S; Deng, Y; Früh, M; González Larriba, JL; Kelsch, C; Lee, A; Moro-Sibilot, D; Nogami, N; Orlandi, F; Patel, H; Piault, E; Reck, M; Rothenstein, J; Shankar, G; Shtivelband, M; Socinski, MA; Wehler, T; Yu, W, 2020)		0.56
" Cytokine-induced killer (CIK) T cell therapy exerts significant cytotoxic effects against cancer cells and reduces the adverse effects of chemotherapy."( Cytokine-induced Killer T Cells Enhance the Cytotoxicity Against Carboplatin-resistant Ovarian Cancer Cells.
Chiu, SC; Chiu, YH; Cho, DY; Hsiao, CH; Lee, LM; Pan, Y; Shih, PH; Wen, YC; Whang-Peng, J, 2020)		0.56
" Unfortunately, platinum-based treatment may lead to ototoxicity, an often-irreversible side effect without a known effective treatment and prevention plan."( Potential use of n-3 PUFAs to prevent oxidative stress-derived ototoxicity caused by platinum-based chemotherapy.
Burotto, M; Caglevic, C; Cortés Fuentes, IA; Frelinghuysen, M; Gormaz, JG; Retamal, MA, 2020)		0.56
"Irreversible sensorineural hearing loss is a common side effect of platinum treatment with the potential to significantly impair the neurocognitive, social and educational development of childhood cancer survivors."( Usefulness of current candidate genetic markers to identify childhood cancer patients at risk for platinum-induced ototoxicity: Results of the European PanCareLIFE cohort study.
Am Zehnhoff-Dinnesen, A; Ansari, M; Beck, JD; Bielack, S; Binder, H; Broer, L; Byrne, J; Clemens, E; Crocco, M; de Vries, ACH; Deuster, D; Elsner, S; Grabow, D; Hasle, H; Hecker-Nolting, S; Kaatsch, P; Kaiser, M; Kenborg, L; Kepak, T; Kompis, M; Kremer, LC; Kruseova, J; Kuehni, CE; Langer, T; Maier, L; Matulat, P; Mayer, B; Parfitt, R; Pluijm, SFM; Rechnitzer, C; Sorg, B; Spix, C; Tillmanns, A; Tissing, WJE; Uitterlinden, AG; van den Heuvel-Eibrink, MM; van der Kooi, AF; van der Pal, H; van Dulmen-den Broeder, E; van Grotel, M; von dem Knesebeck, A; Winther, JF; Zolk, O, 2020)		0.56
" Our results suggest that f-R-ICE is a safe and effective salvage therapy for r/r DLBCL and can be used for older patients and/or those with high CCI scores in outpatient clinics."( Fractionated ifosfamide, carboplatin, and etoposide with rituximab as a safe and effective treatment for relapsed/refractory diffuse large B cell lymphoma with severe comorbidities.
Imai, Y; Shiseki, M; Tanaka, J; Tanaka, N; Yoshinaga, K, 2020)		0.56
"Prior comparisons of chemotherapy adverse events (AEs) by age and performance status (PS) are limited by the traditional maximum grade approach, which ignores low-grade AEs and longitudinal changes."( Expanding Beyond Maximum Grade: Chemotherapy Toxicity over Time by Age and Performance Status in Advanced Non-Small Cell Lung Cancer in CALGB 9730 (Alliance A151729).
Cohen, HJ; Dueck, AC; Feliciano, JL; Gao, J; Hurria, A; Jatoi, A; Miaskowski, C; Novotny, PJ; Sloan, JA; Stinchcombe, TE; Thanarajasingam, G; Walter, LC; Wang, X; Wong, ML; Wood, WA, 2021)		0.62
" Clinical trial identification number: NCT00003117 (CALGB 9730) IMPLICATIONS FOR PRACTICE: The traditional maximum grade approach ignores persistent low-grade adverse events (AEs) and changes over time."( Expanding Beyond Maximum Grade: Chemotherapy Toxicity over Time by Age and Performance Status in Advanced Non-Small Cell Lung Cancer in CALGB 9730 (Alliance A151729).
Cohen, HJ; Dueck, AC; Feliciano, JL; Gao, J; Hurria, A; Jatoi, A; Miaskowski, C; Novotny, PJ; Sloan, JA; Stinchcombe, TE; Thanarajasingam, G; Walter, LC; Wang, X; Wong, ML; Wood, WA, 2021)		0.62
" Ten patients developed grade 3-4 adverse events, including neutropenia (31."( Safety and efficacy of cetuximab-containing chemotherapy after immune checkpoint inhibitors for patients with squamous cell carcinoma of the head and neck: a single-center retrospective study.
Doi, K; Fumita, S; Haratani, K; Hayashi, H; Ishikawa, K; Iwasa, T; Kanemura, H; Kitano, M; Kurosaki, T; Mitani, S; Nakagawa, K; Nishimura, Y; Otsuki, N; Suzuki, S; Tanaka, K; Yoshida, T, 2021)		0.62
"The present study found that pirfenidone combined with carboplatin-based regimens or ICIs might be safe first-line chemotherapy for patients with IPF and NSCLC."( Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study.
Akazawa, Y; Ishijima, M; Kanazu, M; Kuge, T; Mori, M; Okabe, F; Uenami, T; Yamaguchi, T; Yamamoto, Y; Yano, Y, 2020)		0.56
" Currently there is no evidence or case reports to guide the safe administration of chemotherapy in MCAS patients."( Safe administration of chemotherapy in mast cell activation syndrome.
Krell, J; Lythgoe, MP; McNeish, IA; Tookman, L, 2021)		0.62
") are highly effective chemotherapeutic drugs used for the treatment of several types of malignancies, but their application and dosage are limited by their toxic effects on various systems, including neurotoxicity."( Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics-A Review.
Mihailovic, V; Rosic, G; Selakovic, D; Stankovic, JSK, 2020)		0.56
"Hearing loss is a permanent and debilitating side-effect of a range of interventions commonly used in the treatment of childhood cancers, primarily ototoxic medications such as cisplatin."( Ototoxicity-induced hearing loss and quality of life in survivors of paediatric cancer.
Abiodun, A; Al-Malky, G; Brock, P; Edwards, L; Rajput, K; Simpkin, P, 2020)		0.56
"1%) toxic deaths were ascribed to adjuvant chemotherapy-related complications."( Safety and efficacy of concurrent carboplatin during full-dose craniospinal irradiation for high-risk/metastatic medulloblastoma in a resource-limited setting.
Bhat, V; Chatterjee, A; Chinnaswamy, G; Epari, S; Goda, JS; Gupta, T; Jalali, R; Khatua, S; Krishnatry, R; Kurkure, P; Moiyadi, A; Patil, V; Prasad, M; Sahay, A; Shetty, P; Sinha, S; Vora, T, 2021)		0.62
"The primary endpoint was the 1-year survival rate, with secondary endpoints of response rate (RR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and adverse event rate."( Efficacy and safety of carboplatin and pemetrexed followed by maintenance with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer: A single-arm, open-label, multicenter, phase II study.
Hara, Y; Kaneko, T; Kobayashi, N; Manabe, S; Miyazawa, N; Murakami, S; Nishikawa, M; Saito, H; Shinkai, M; Shinoda, M; Tomaru, K, 2021)		0.62
" This study aimed to compare serum carboplatin concentrations in dogs after SC and IVD and to monitor any adverse events."( Serum concentration and safety of intravenous drip versus subcutaneous administration of carboplatin in dogs.
Iwano, M; Kawarai, S; Kayanuma, H; Maruo, T; Orito, K; Sadahiro, K, 2021)		0.62
"Clinical trials report adverse events (AEs) in a dense table focusing on the frequency of 'worst grade' AEs experienced over the duration of treatment."( Reporting the trajectories of adverse events over the entire treatment course in patients with recurrent platinum-sensitive ovarian cancer treated with platinum-based combination chemotherapy regimens: A graphical approach to trial adverse event reporting
Francis, KE; Friedlander, M; Gebski, V; Lee, CK; Lord, SJ; Pujade-Lauraine, E, 2021)		0.62
" Treatment response, European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30 (EORTC QLQ-C30), progression-free survival (PFS), overall survival (OS), and adverse events were assessed during the follow-up."( Drug-eluting bead bronchial arterial chemoembolization vs. chemotherapy in treating advanced non-small cell lung cancer: comparison of treatment efficacy, safety and quality of life.
Bao, PT; Lin, H; Liu, XF; Mu, M; Pan, P; Tian, FF; Wang, Q; Zhang, R; Zhao, WG, 2021)		0.62
" Furthermore, two groups all exhibited mild and tolerable adverse events."( Drug-eluting bead bronchial arterial chemoembolization vs. chemotherapy in treating advanced non-small cell lung cancer: comparison of treatment efficacy, safety and quality of life.
Bao, PT; Lin, H; Liu, XF; Mu, M; Pan, P; Tian, FF; Wang, Q; Zhang, R; Zhao, WG, 2021)		0.62
"The primary outcome was treatment feasibility, defined as the ability to complete 6 chemotherapy cycles without disease progression, premature toxic effects-related treatment discontinuation, or death."( Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin Plus Paclitaxel for Vulnerable Older Adult Women With Ovarian Cancer: A GINECO/GCIG Randomized Clinical Trial.
Bourbouloux, E; Brachet, PE; D'Hondt, V; Falandry, C; Freyer, G; Herrstedt, J; Lortholary, A; Lorusso, D; Malaurie, E; Mouret-Reynier, MA; Mourey, L; Pujade-Lauraine, E; Rousseau, F; Savoye, AM; Stefani, L; Sverdlin, R; Tinquaut, F; Trédan, O; Venat-Bouvet, L; Zannetti, A, 2021)		0.62
" Treatment-related adverse events were less common with the standard every-3-weeks combination (17 of 40 [43%]) than single-agent carboplatin or weekly combination therapy (both 23 of 40 [58%])."( Efficacy and Safety of First-line Single-Agent Carboplatin vs Carboplatin Plus Paclitaxel for Vulnerable Older Adult Women With Ovarian Cancer: A GINECO/GCIG Randomized Clinical Trial.
Bourbouloux, E; Brachet, PE; D'Hondt, V; Falandry, C; Freyer, G; Herrstedt, J; Lortholary, A; Lorusso, D; Malaurie, E; Mouret-Reynier, MA; Mourey, L; Pujade-Lauraine, E; Rousseau, F; Savoye, AM; Stefani, L; Sverdlin, R; Tinquaut, F; Trédan, O; Venat-Bouvet, L; Zannetti, A, 2021)		0.62
" The safety profile of MB02 and EU-bevacizumab regarding nature, frequency and severity of the adverse events (AE) was comparable."( Efficacy, Safety and Immunogenicity of MB02 (Bevacizumab Biosimilar) versus Reference Bevacizumab in Advanced Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study (STELLA).
Andric, Z; Bellala, RS; Charoentum, C; Costamilan, RC; Del Campo García, A; Florez, A; Fulop, A; Hyder Ali, IA; Katgi, N; Lopez Chuken, YA; Makharadze, T; Millan, S; Paravisini, A; Poddubskaya, E; Reyes-Igama, J; Rumyana, I; Syrigos, K; Trukhin, D; Yañez Ruiz, EP, 2021)		0.62
" Related adverse effects of platinum-containing chemotherapies involved gastrointestinal reaction, myelosuppression and liver function damage."( The Impact of Platinum-Containing Chemotherapies in Advanced Triple-Negative Breast Cancer: Meta-Analytical Approach to Evaluating Its Efficacy and Safety.
Han, XH; Liu, S; Shi, YY; Yang, R, 2021)		0.62
" Adverse events unrelated to progression leading to study drug discontinuation occurred in 25 (9."( Efficacy and safety of first-line veliparib and carboplatin-paclitaxel in patients with HER2- advanced germline BRCA+ breast cancer: Subgroup analysis of a randomised clinical trial.
Arun, BK; Ayoub, JP; Bach, BA; Bell-McGuinn, KM; Diéras, V; Friedlander, M; Han, HS; Kaufman, B; Kundu, MG; Maag, D; Puhalla, SL; Ratajczak, CK; Wildiers, H, 2021)		0.62
" Treatment-emergent adverse events (TEAEs) were reported for 94."( Efficacy and Safety of Bevacizumab Biosimilar FKB238 Versus Originator Bevacizumab: Results from AVANA, a Phase III Trial in Patients with Non-Squamous Non-Small-Cell Lung Cancer (non-sq-NSCLC).
Abert, I; Andric, Z; Bashir, Z; Bondarenko, IN; Dvorkin, M; Fu, D; Galic, K; Galiulin, R; Jones, S; Kassalow, LM; Kuchava, V; Sriuranpong, V; Syrigos, K; Trukhin, D; Zhavrid, E, 2021)		0.62
" No treatment-related adverse events of grade 3 or higher were observed."( Efficacy and safety of 5 mg olanzapine for nausea and vomiting management in cancer patients receiving carboplatin: integrated study of three prospective multicenter phase II trials.
Abe, M; Fujita, Y; Hayasaki, Y; Hirose, C; Iihara, H; Imai, H; Inui, N; Karayama, M; Kawazoe, H; Morishige, KI; Nakamura, K; Ohno, Y; Suda, T; Suzuki, A; Tanaka, K; Uozumi, R; Yamamoto, S, 2021)		0.62
"The findings suggest that antiemetic regimens containing low-dose (5 mg) olanzapine could be effective and safe for patients receiving carboplatin-based chemotherapy."( Efficacy and safety of 5 mg olanzapine for nausea and vomiting management in cancer patients receiving carboplatin: integrated study of three prospective multicenter phase II trials.
Abe, M; Fujita, Y; Hayasaki, Y; Hirose, C; Iihara, H; Imai, H; Inui, N; Karayama, M; Kawazoe, H; Morishige, KI; Nakamura, K; Ohno, Y; Suda, T; Suzuki, A; Tanaka, K; Uozumi, R; Yamamoto, S, 2021)		0.62
" Treatment-emergent adverse events of maximum grade 3 or 4 occurred in 61."( First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial.
Bai, C; Chang, X; Chen, W; Feng, J; Ge, M; Guo, Y; He, X; Huang, X; Li, Z; Lin, T; Liu, Y; Luo, Y; Shen, L; Sun, Y; Wang, L; Xue, K; Yang, K; Zeng, Y; Zhang, Q; Zhu, X, 2021)		0.62
"CHANGE-2 showed an improved median PFS, median OS and ORR with the addition of cetuximab to a modified platinum/5-fluorouracil regimen, with no new or unexpected safety findings, thereby confirming CT plus cetuximab as an effective and safe 1L treatment for Chinese patients with R/M SCCHN."( First-line treatment with chemotherapy plus cetuximab in Chinese patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety results of the randomised, phase III CHANGE-2 trial.
Bai, C; Chang, X; Chen, W; Feng, J; Ge, M; Guo, Y; He, X; Huang, X; Li, Z; Lin, T; Liu, Y; Luo, Y; Shen, L; Sun, Y; Wang, L; Xue, K; Yang, K; Zeng, Y; Zhang, Q; Zhu, X, 2021)		0.62
" Safety was assessed by adverse events (AEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs)."( Safety and efficacy of dendritic cell-based immunotherapy (DCVAC/LuCa) combined with carboplatin/pemetrexed for patients with advanced non-squamous non-small-cell lung cancer without oncogenic drivers.
Cao, S; Han, B; Ling, X; Wang, H; Xu, J; Zhang, B; Zhang, X; Zhong, H; Zhong, R, 2022)		0.72
" Toxicity was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE v5."( Effect of XPD and TP53 Gene Polymorphisms on the Risk of Platinum-Based Chemotherapy Induced Toxicity in Bangladeshi Lung Cancer Patients.
Bushra, YU; Kabir, Y; Nairuz, T, 2021)		0.62
" DCVAC/OvCa showed a good safety profile with treatment-emergent adverse events related to DCVAC/OvCa in 2 of 34 patients (5."( Safety and efficacy of dendritic cell-based immunotherapy DCVAC/OvCa added to first-line chemotherapy (carboplatin plus paclitaxel) for epithelial ovarian cancer: a phase 2, open-label, multicenter, randomized trial.
Bartos, P; Bartunkova, J; Chovanec, J; Cibula, D; Fucikova, J; Hraska, M; Hrnciarova, T; Kieszko, D; Klat, J; Knapp, P; Korolkiewicz, RP; Mallmann, P; Melichar, B; Minar, L; Novotny, Z; Pluta, M; Rob, L; Spacek, J; Spisek, R; Valha, P, 2022)		0.72
"Irreversible bilateral sensorineural hearing loss is a common side effect of platinum compounds."( Long-term auditory follow-up in the management of pediatric platinum-induced ototoxicity.
Brigato, F; De Corso, E; Fetoni, AR; Galli, J; Lucidi, D; Ruggiero, A; Scarano, E; Sergi, B, 2022)		0.72
"The most frequently reported adverse events for bevacizumab were hypertension (55%), epistaxis (32%) and proteinuria (21%)."( Prospective non-interventional BELOVA/BGOG-ov16 study on safety of frontline bevacizumab in elderly patients with FIGO stage IV ovarian cancer: a study of the Belgian and Luxembourg Gynaecological Oncology Group.
Claes, N; De Maeseneer, D; De Waele, S; Debrock, G; Denys, H; Dirix, L; Gennigens, C; Graas, MP; Honhon, B; Lamot, C; Martinez Mena, C; Mebis, J; Pelgrims, G; Spoormans, I; Van den Bulck, H; van Gorp, T; Van Nieuwenhuysen, E; Van Steenberghe, M; Vergote, I; Verhoeven, D; Vroman, P; Vulsteke, C; Vuylsteke, P, 2022)		0.72
" Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86."( Randomized double-blind clinical trial comparing safety and efficacy of the biosimilar BCD-021 with reference bevacizumab.
Adamchuk, GA; Fadeeva, NV; Kalloli, M; Kryukov, F; Matrosova, MP; Nagarkar, R; Roy, B; Shelepen, KG; Shustova, MS; Stroyakovskiy, DL; Voevodin, GD; Zhuravleva, D, 2022)		0.72
" Kidney adverse effects may include acute kidney injury (via tubular injury, tubulointerstitial nephritis, glomerular disease and thrombotic microangiopathy), long-term kidney function loss and CKD, and electrolyte disturbances."( Conventional Chemotherapy Nephrotoxicity.
Daher, A; Gupta, S; Kitchlu, A; Portales-Castillo, I, 2021)		0.62
" The primary endpoint was disease-free survival rate at 24 months, whereas secondary endpoints included major pathological response (MPR) and pathologic complete response (pCR) rates, the proportion of patients who achieved tumor downstaging, overall survival, objective response rate (ORR), and adverse effects."( Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage IIIA/IIIB non-small cell lung cancer: a single-arm, phase 2 trial.
Guo, Y; Lin, X; Liu, Y; Ma, K; Ma, X; Qiu, S; Shao, G; Sun, C; Wang, X; Xu, Y; Yang, Z; Zhang, P, 2023)		0.91
" Moreover, 14 patients (70%) experienced grade 1 or 2 neoadjuvant treatment-related adverse events (TRAEs), whereas 6 (30%) experienced grade 3 TRAEs."( Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage IIIA/IIIB non-small cell lung cancer: a single-arm, phase 2 trial.
Guo, Y; Lin, X; Liu, Y; Ma, K; Ma, X; Qiu, S; Shao, G; Sun, C; Wang, X; Xu, Y; Yang, Z; Zhang, P, 2023)		0.91
" Therefore, the current study suggests that neoadjuvant chemoimmunotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC."( Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage IIIA/IIIB non-small cell lung cancer: a single-arm, phase 2 trial.
Guo, Y; Lin, X; Liu, Y; Ma, K; Ma, X; Qiu, S; Shao, G; Sun, C; Wang, X; Xu, Y; Yang, Z; Zhang, P, 2023)		0.91
" Random-effects model will be used to pool data for patient-reported outcomes including survival rate, OS, PFS and adverse events."( Effectiveness and safety of weekly therapy versus 3-weekly therapy of paclitaxel plus carboplatin in women with ovarian cancer: a protocol of systematic review and meta-analysis.
Cai, B; Dang, Y; Fu, Y; Li, Y; Lin, R; Liu, Q; Mao, B; Qiu, W; Tuo, S, 2022)		0.72
" In consideration of safety, the most frequent adverse events were peripheral neuropathy (37."( Efficacy, safety and prognostic factors of camrelizumab plus carboplatin and pemetrexed chemotherapy in advanced lung adenocarcinoma patients.
Bao, Q; Chen, Y; Deng, R; Fu, Y; He, Y; Huang, M; Li, C; Liu, M; Liu, Y; Lv, J; Lv, Z; Miao, Y; Wang, F; Wang, L; Wang, Q; Zhang, C; Zhang, T; Zhang, W; Zhang, Z; Zhao, X; Zhou, H, 2022)		0.72
"Camrelizumab plus CP chemotherapy achieves favourable efficacy and tolerable adverse events in advanced lung adenocarcinoma patients."( Efficacy, safety and prognostic factors of camrelizumab plus carboplatin and pemetrexed chemotherapy in advanced lung adenocarcinoma patients.
Bao, Q; Chen, Y; Deng, R; Fu, Y; He, Y; Huang, M; Li, C; Liu, M; Liu, Y; Lv, J; Lv, Z; Miao, Y; Wang, F; Wang, L; Wang, Q; Zhang, C; Zhang, T; Zhang, W; Zhang, Z; Zhao, X; Zhou, H, 2022)		0.72
" The adverse event profile was consistent with the known toxicity profile of PCb, with no differences between the 2 strata."( Safety and Tolerability of Carboplatin and Paclitaxel in Cancer Patients with HIV (AMC-078), an AIDS Malignancy Consortium (AMC) Study.
Bimali, M; Chiao, E; Cooley, T; Deeken, J; Haigentz, M; Henry, D; Moore, P; Ramos, J; Ratner, L; Rubinstein, P; Rudek, M; Sparano, J, 2022)		0.72
" It reduces the systemic adverse toxicity issues of drugs carrier, making this system ideal for nasopharyngeal cancer treatment."( Self-assembling porphyrin conjugate-carboplatin(IV) prodrug nanoparticles for enhancing high efficacy nasopharyngeal cancer and low systemic toxicity.
Peng, Q; Su, R; Wang, W; Zhang, X, 2022)		0.72
" Grade ≥ 3 hematological adverse events occurred as follows: decreased white blood cells in 52."( Efficacy and safety of amrubicin monotherapy after atezolizumab plus carboplatin and etoposide in patients with relapsed small-cell lung cancer.
Imai, H; Kagamu, H; Kaira, K; Kanazawa, K; Kishikawa, T; Minato, K; Minemura, H; Mouri, A; Nagai, Y; Shiihara, J; Shiono, A; Taniguchi, H; Tsuda, T; Wasamoto, S; Yamada, Y; Yamaguchi, O, 2022)		0.72
" This is the first case of multi-organs, multi-time point immune-related adverse events (irAE) in perioperative NSCLC patients who received neoadjuvant chemoimmunotherapy."( Multi-organs perioperative immune-related adverse events and postoperative bronchial anastomotic fistula in a patient receiving neoadjuvant immunotherapy with NSCLC.
Liu, H; Long, Y; Lyu, X; Ma, D; Qin, Y; Shi, J; Tang, B; Wang, M; Xu, Y, 2022)		0.72
" However, due to the limitations of adverse reaction and lacking of targeting ability, the chemotherapy of ovarian cancer is still poorly effective."( Estrone-Conjugated PEGylated Liposome Co-Loaded Paclitaxel and Carboplatin Improve Anti-Tumor Efficacy in Ovarian Cancer and Reduce Acute Toxicity of Chemo-Drugs.
Guo, X; Jia, J; Liu, R; Miao, D; Pei, J; Shen, Y; Tang, H; Xie, Y; Zheng, Y; Zhu, M, 2022)		0.72
"05) has been associated with PTX-induced adverse effects in Caucasians, while limited studies were reported in Asians."( Paclitaxel exposure-toxicity analysis reveals a pharmacokinetic determinant for dose-limiting neutropenia in East-Asian solid tumor patients: results from two prospective, phase II studies.
Fang, W; He, H; Hong, S; Huang, Y; Lin, Y; Lin, Z; Ma, Y; Salamone, SJ; Wu, Y; Xue, J; Yang, Y; Zhang, L; Zhang, Y; Zhao, H, 2022)		0.72
" Myelosuppression was the most common adverse event."( HIPEC after neoadjuvant chemotherapy is associated with acceptable toxicity and favorable quality of life in newly diagnosed advanced ovarian cancer patients.
Hsu, FC; Kelly, MG; Lentz, SS; Levine, EA; Menzies, AV; Usher, EC, 2022)		0.72
" The incidence of grade 3 or higher adverse events (AEs) was 58."( Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A multi-center, prospective study (ACTION-2).
Chen, L; Chen, Y; Deng, P; Dong, Y; Han, B; Kong, T; Liu, D; Qian, F; Yang, H; Zhang, B; Zhang, W; Zhang, Y, 2022)		0.72
" Treatment-related adverse events were less frequent in the PD-1 inhibitor group than in the carboplatin-gemcitabine group (57."( The efficacy and safety of first-line treatment in cisplatin-ineligible advanced upper tract urothelial carcinoma patients: a comparison of PD-1 inhibitor and carboplatin plus gemcitabine chemotherapy.
Bao, Y; Cai, M; Chen, M; Chen, Z; Fu, C; Guo, J; Hu, H; Huang, J; Huang, Z; Jiang, S; Li, C; Su, R; Wang, Z; Wei, Q; Xue, W; Yuan, Y; Zheng, B, 2022)		0.72
" The safety profile was acceptable with 73% Grade 3-4 treatment-related adverse events."( Safety and efficacy of avelumab plus carboplatin in patients with metastatic castration-resistant prostate cancer in an open-label Phase Ib study.
Alonso, J; Bellmunt, J; Cano, L; Corbera, A; Font, A; Galtes, S; Juan, O; Juanpere, N; Maroto, P; Martin, C; Martinez, G; Martinez-Garcia, M; Mellado, B; Orrillo, M; Querol, R; Reig, O; Rios-Hoyo, A; Rodriguez-Vida, A; Taus, A, 2023)		0.91
" CP-D is a beneficial and safe method in treating platinum-sensitive recurrent EOC patients with CP-induced HSR."( Toxicity management and efficacy of carboplatin desensitization therapy for recurrent epithelial ovarian carcinoma: A real-world study.
Ak, N; Aydiner, A; Doğan, İ; Ferhatoğlu, F; Khanmammadov, N; Paksoy, N; Yildiz, A, 2022)		0.72
"Hearing damage is one of the main toxic effects of platinum compounds, it derives from the irreversible degeneration of hair cells of the ear."( Platinum-induced ototoxicity in pediatric cancer survivors: GSTP1 c.313A>G variant association.
Ahmed, R; Attia, M; Hanna, D; Kamal, NM; Oshi, MAM; Rifky, E; Sherief, LM, 2022)		0.72
" The primary endpoints were grade ≥ 3 adverse events (AEs) and overall survival (OS)."( Safety and efficacy of paclitaxel plus carboplatin versus paclitaxel plus cisplatin in neoadjuvant chemoradiotherapy for patients with locally advanced esophageal carcinoma: a retrospective study.
Chen, X; Han, Y; Jiang, L; Leng, X; Peng, L; Wan, G; Wang, Q; Wang, Y; Wu, L; Zhu, J, 2022)		0.72
" CP and CG were compared in terms of progression-free survival (PFS), overall survival (OS), and incidence of adverse events (AEs)."( Efficacy and Safety of First-line Carboplatin-paclitaxel and Carboplatin-gemcitabine in Patients With Advanced Triple-negative Breast Cancer: A Monocentric, Retrospective Comparison.
Bianchi, GV; Cantarelli, B; Capri, G; de Braud, F; Depretto, C; Fucà, G; Leporati, R; Ligorio, F; Lobefaro, R; Manoukian, S; Mariani, L; Peverelli, G; Presti, D; Pruneri, G; Rametta, A; Scaperrotta, G; Vernieri, C; Vingiani, A; Zattarin, E, 2023)		0.91
"Immune-related adverse events (irAEs) arising from immune checkpoint inhibitor (ICI) cancer therapy may potentially predict improved outcomes."( Association of Immune-Related Adverse Events With Efficacy of Atezolizumab in Patients With Non-Small Cell Lung Cancer: Pooled Analyses of the Phase 3 IMpower130, IMpower132, and IMpower150 Randomized Clinical Trials.
Bara, I; Cappuzzo, F; Finley, GG; Jotte, RM; Kaul, MD; Mok, TSK; Nishio, M; Paranthaman, N; Reck, M; Socinski, MA; West, HJ; Yu, W, 2023)		0.91
" Adverse events (AEs) were examined."( Effectiveness and safety of nab-paclitaxel and platinum as first-line chemotherapy for ovarian cancer: a retrospective study.
Han, Z; Hong, Z; Li, S; Qin, Y; Wang, L; Wang, X; Zhu, D, 2023)		0.91
" Only one patient discontinued chemotherapy due to an adverse event of proteinuria."( Efficacy and Safety of Platinum-based Chemotherapy With Bevacizumab Followed by Bevacizumab Maintenance for Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer During PARP Inhibitor Therapy: A Multicenter Retrospective Study.
Abe, M; Aida, T; Baba, T; Chiba, Y; Kagabu, M; Kaido, Y; Nagasawa, T; Shoji, T; Takahashi, F; Takatori, E, 2023)		0.91
" The secondary endpoint was specific adverse events, including vomiting, fatigue, thrombocytopenia, constipation, and decreased appetite; hence we depicted the specific toxicity profile of each regimen."( Efficacy and toxicity profile of first-line treatment for extensive-stage small cell lung cancer: A Bayesian network meta-analysis.
Kang, K; Lin, G; Lu, Y; Luo, R; Wang, H; Yao, Z, 2023)		0.91
" Results suggest that SLCO1B3 and LIG3 variants are associated with the risk of adverse effects in patients receiving carboplatin-paclitaxel treatment, the GSTP1 variant may affect the treatment response and ABCB1 and OPRM1 variants may influence the prognosis."( Toxicity and therapy outcome associations in LIG3, SLCO1B3, ABCB1, OPRM1 and GSTP1 in high-grade serous ovarian cancer.
Deng, F; Hautaniemi, S; Huhtinen, K; Hynninen, J; Laasik, M; Lapatto, L; Lehtonen, R; Li, Y; Niemi, M; Salminen, L, 2023)		0.91
" Compared to VEC alone, similar rates of neutropenia, anemia, and thrombocytopenia were seen, with no toxic deaths."( Toxicity and feasibility of vincristine, etoposide, and carboplatin alternating with vincristine, doxorubicin, and cyclophosphamide in children with advanced retinoblastoma in Guatemala.
Alejos, A; Giron, V; Graff, Z; Luna-Fineman, S; Miller, K; Pixtun, D, 2023)		0.91
"9%) with adverse events recovered without sequelae, and no treatment-related death occurred."( Safety and Tolerability of Weekly Genexol-PM, a Cremophor-Free Polymeric Micelle Formulation of Paclitaxel, with Carboplatin in Gynecologic Cancer: A Phase I Study.
Kim, YM; Lee, SW; Lee, YJ; Nam, SH, 2023)		0.91
"The present findings show that carboplatin has adverse effects on AMH, ovarian tissue apoptosis, and OS parameters."( The role of oxidative stress in chemotherapy-induced gonadotoxicity in a rat model, and the protective effects of Nigella Sativa oil on oxidative stress, the anti-Müllerian hormone level, and apoptosis.
Alisik, M; Atasever, M; Cetinkaya, K; Coskun, B; Erisgin, Z; Ozer, C; Sonmez, C, 2023)		0.91
" Here we report a case of a patient who experienced immune-mediated adverse effects from checkpoint blockade therapy and subsequently responded to chemotherapy."( Successful treatment with carboplatin and paclitaxel in melanoma progression after immune-related adverse events.
Dülgar, Ö; Elleson, KM; Markowitz, J; Saha, A, 2023)		0.91
" The incidence of adverse events, especially those related to antiangiogenic therapy, was higher in the Apa+ddTCb group."( Efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin in neoadjuvant therapy for locally advanced triple-negative breast cancer: A prospective cohort study with propensity-matched analysis.
Chai, Y; He, M; Jiang, M; Li, Q; Liu, J; Luo, Y; Ma, F; Ou, K; Qi, L; Wang, X; Wang, Y; Xu, B; Yuan, P; Zhang, P, 2024)		1.44
"Bevacizumab, Ovarian cancer, Platinum-based chemotherapy, Tolerability, Adverse clinical events."( Efficacy and Safety of Combined Chemotherapy Regimens with Bevacizumab in Platinum-sensitive Ovarian Cancers.
Ates, O; Buyukkor, M; Tay, F, 2023)		0.91

Pharmacokinetics

The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles. Measuring GFR with iohexol to better dosecarboplatin is unlikely to alter the safety or efficacy of chemotherapy through pharmacokinetic drug-drug interactions.

ExcerptReferenceRelevance
" Cmax in blood was seen one hour after ip in patients with a normal peritoneum, and was seen between 4 and 6 hours after ip in patients with peritonitis carcinomatosa."( [Usefulness of intraperitoneal carboplatin administration-- pharmacokinetic analysis].
Adachi, S; Furuki, K; Hirano, Y; Itani, Y; Ito, K; Kato, Y; Kiyozuka, Y; Noda, T; Tamori, N, 1992)		0.28
" Pt was excreted to urine and reached to the peak concentration at 4 hr."( [Pharmacokinetics of carboplatin after intraperitoneal administration and clinical effect in ovarian cancer].
Hando, T; Hirokawa, M; Ohno, M, 1992)		0.28
" Median pharmacokinetic parameters for ultrafilterable platinum were as follows: clearance 45."( The pharmacokinetics of high-dose carboplatin in pediatric patients with cancer.
Madden, T; Rodman, JH; Santana, VM; Sunderland, M, 1992)		0.28
" The terminal half-life of total platinum is comparable between the 2 compounds (5."( Clinical pharmacokinetics of carboplatin.
van der Vijgh, WJ, 1991)		0.28
" Elimination half-life of carboplatinum of 20."( [Pharmacokinetics of carboplatin after intraperitoneal administration].
Czejka, M; Jäger, W; Schüller, J; Teherani, D, 1991)		0.28
" Pharmacokinetic analysis of total and ultrafiltrable platinum (UFPt) was performed by atomic absorption spectrophotometry."( Continuous infusion carboplatin on a 21-day schedule: a phase I and pharmacokinetic study.
de Vries, EG; Meijer, S; Mulder, NH; Postmus, PE; Sleijfer, DT; Smit, EF; Terheggen, PM; Uges, DR; Willemse, PH, 1991)		0.28
" The study includes a pharmacokinetic analysis of CBDCA in three patients."( Clinical trial and pharmacokinetics of carboplatin 560 mg/m2 in children.
Bastian, G; Brugières, L; Doz, F; Lemerle, J; Quintana, E; Zucker, JM, 1990)		0.28
" A pharmacokinetic study during the second course revealed low levels of carboplatin in the cerebrospinal fluid."( Complete remission of brain metastases of ovarian cancer following high-dose carboplatin: a case report and pharmacokinetic study.
Beynen, JH; Boogerd, W; Rodenhuis, S; Ten Bokkel Huinink, WW; Vlasveld, LT, 1990)		0.28
" Carboplatin was given on either day 1 or day 2 of each course and pharmacokinetic studies were carried out in each patient on two courses."( Carboplatin and etoposide pharmacokinetics in patients with testicular teratoma.
Boxall, FE; Calvert, AH; Eeles, RA; Gumbrell, LA; Horwich, A; Newell, DR, 1989)		0.28
" This study, in addition, supports our concept of individualized dosing of carboplatin and the underlying pharmacokinetic/pharmacodynamic relationships and represents an interesting pharmacodynamic and quantitative approach to studying potential drug-drug interactions and defining appropriate dosages for combination chemotherapy."( A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide.
Abrams, JS; Aisner, J; Belani, CP; Egorin, MJ; Eisenberger, M; Hiponia, D; Van Echo, DA, 1989)		0.28
" This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds."( Pharmacokinetics of (glycolate-0,0')-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin.
Bungo, M; Eguchi, K; Fujiwara, Y; Fukuda, M; Horichi, N; Niimi, S; Ohe, Y; Sasaki, Y; Shinkai, T; Tamura, T, 1989)		0.28
"A physiologic pharmacokinetic model describing drug disposition in the isolated perfused porcine skin flap (IPPSF) is derived."( Definition of a physiologic pharmacokinetic model of cutaneous drug distribution using the isolated perfused porcine skin flap.
Riviere, JE; Williams, PL, 1989)		0.28
"A survey of investigations performed by our group over the last few years whose goal was to obtain analytical, clinical and pharmacokinetic data concerning cancer chemotherapy with Pt-based drugs is reported."( Clinical, analytical and pharmacokinetic aspects in cancer chemotherapy with platinum coordination compounds.
Alimonti, A; Caroli, S; Castello, MA; Dominici, C; La Torre, F; Petrucci, F, 1989)		0.28
" Estimates of pharmacokinetic parameters determined using either compartmental or non-compartmental methods were comparable."( Pharmacokinetics of unchanged carboplatin (CBDCA) in patients with small cell lung carcinoma.
Bishop, JF; Hillcoat, BL; Morstyn, G; Olver, IN; Reece, PA; Stafford, I, 1987)		0.27
"6 L/m2/hr) were also independent of dose; AUC and Cmax increased proportionally to dose."( Clinical pharmacokinetics of carboplatin.
Ishikawa, K; Kimura, K; Mase, H; Oguri, S; Sakakibara, T; Shimizu, T; Smyth, RD, 1988)		0.27
" The results indicate that the major pharmacokinetic differences between Carboplatin and cisplatin relate to their renal handling and their reactivity with macromolecules."( The comparative pharmacokinetics of carboplatin and cisplatin in mice and rats.
Boxall, FE; Harrap, KR; Newell, DR; Siddik, ZH, 1987)		0.27
" Calculated pharmacokinetic parameters (peak concentrations, half-lives, areas under the curve) were compared with the corresponding values in patients at the maximal tolerated dose."( Comparative pharmacokinetics of cisplatin and three analogues in mice and humans.
Elferink, F; Klein, I; Pinedo, HM; van der Vijgh, WJ; van Hennik, MB; Vermorken, JB; Winograd, B, 1987)		0.27
"Plasma protein binding and pharmacokinetic parameters of CHIP (cis-dichloro-trans-dihydroxy-bis-isopropylamine platinum IV) and CBDCA (cis-diammine-1,1-cyclobutane dicarboxylate platinum II) were investigated in male Wistar rats."( Pharmacokinetics and plasma protein binding of two platinum cytostatics CHIP and CBDCA in rats.
Drobník, J; Kvĕtina, J; Láznícek, M; Láznícková, A, 1986)		0.27
" Pharmacokinetic profiles suggest a possible therapeutic advantage for giving the drug intraperitoneally for the treatment of tumour nodules situated in the peritoneum."( Phase I study and pharmacokinetics of intraperitoneal carboplatin.
Dubbelman, R; Franklin, H; Klein, I; McVie, JG; ten Bokkel Huinink, W; van der Vijgh, W, 1985)		0.27
" Following cessation of the infusion, a half-life of 170 +/- 34 min (S."( A phase I and pharmacokinetic study of diamminecyclobutane-dicarboxylatoplatinum (NSC 241240).
Collins, JM; Corden, BJ; Curt, GA; Grygiel, JJ; Myers, CE; Ozols, RF; Tell, DT; Weiss, RB, 1983)		0.27
" Pharmacokinetic studies have been performed in patients receiving CBDCA (20 to 520 mg/sq m) as a 1-hr infusion without hydration or diuresis."( Pharmacokinetics of cis-diammine-1,1-cyclobutane dicarboxylate platinum(II) in patients with normal and impaired renal function.
Calvert, AH; Chadwick, R; Harland, SJ; Harrap, KR; Newell, DR; Siddik, ZH, 1984)		0.27
" The collected experience emphasizes the many individual variables encountered in clinical practice complicating the effort of correlating pharmacokinetic data with clinical results."( Pharmacokinetic studies in lung cancer patients.
Cattaneo, MT; Piazza, E; Varini, M, 1984)		0.27
" Plasma pharmacokinetics have shown that concurrent carboplatin and radiotherapy do not alter the pharmacokinetic behavior of paclitaxel compared with single-agent data."( Feasibility and pharmacokinetics of paclitaxel, carboplatin, and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck and for regionally advanced non-small cell lung cancer.
Aisner, J; Belani, CP; Conley, B; Egorin, MJ; Engstrom, C; Hiponia, D; Kearns, C; Zuhowski, E, 1995)		0.29
" Pharmacokinetic analysis showed significantly lower measured versus predicted AUC values."( A clinical and pharmacokinetic study of high-dose carboplatin, paclitaxel, granulocyte colony-stimulating factor, and peripheral blood stem cells in patients with unresectable or metastatic cancer.
Bentley, S; Bernard, S; Brecher, M; Graham, M; Johnston, C; Serody, J; Shea, T; Steagall, A; Vaisman, A; Wiley, J, 1995)		0.29
" However, some studies also have suggested that the area under the plasma concentration-time curve (AUC) of carboplatin is lower than that expected, raising the possibility of a pharmacokinetic interaction."( Carboplatin in combination with paclitaxel in advanced ovarian cancer: dose determination and pharmacokinetic and pharmacodynamic interactions.
Bailey, NP; Boddy, A; Calvert, AH; Chapman, F; Gumbrell, L; Hughes, A; Humphreys, A; Robson, L; Siddiqui, N; Thomas, H, 1995)		0.29
" A terminal elimination half-life of 13-27 h was noted for post-infusion UFPt."( A phase I and pharmacokinetics study of prolonged ambulatory-infusion carboplatin.
Bishop, JF; Millward, MJ; Olver, IN; Stokes, KH; Webster, LK, 1995)		0.29
"Seven patients with recurrent gynecological malignancies (2 cervical, 2 endometrial, 3 ovarian) treated with CDDP at the initial chemotherapy were studied for the pharmacokinetic analysis of platinum (Pt) and changes of blood biochemistry in the continuous CDDP-CBDCA infusion therapy."( [Pharmacokinetic analysis of platinum in the continuous CDDP-CBDCA treatment; its relation to the changes of blood biochemistry].
Chen, JT; Hasumi, K, 1995)		0.29
" The terminal half-life (t1/2) of this drug in plasma ultrafiltrate (3."( Pharmacokinetic evaluation of zeniplatin in humans.
Amorusi, P; Birkhofer, M; Budman, DR; DeMarco, LC; Gal, D; Lathia, C; Lichtman, S; Lovecchio, J; Vinciguerra, V; Weiselberg, L, 1995)		0.29
" Extensive data for carboplatin, and more limited results with cisplatin, indicate that there is significant inter-patient pharmacokinetic variability such that adaptive dosing may be necessary for the optimal use of these drugs."( The comparative pharmacokinetics and pharmacodynamics of cisplatin and carboplatin in paediatric patients: a review.
Bin, P; Boddy, AV; English, MW; Newell, DR; Pearson, AD; Price, L; Tilby, MJ, )		0.13
" In order to correlate myelosuppression with pharmacokinetic parameters, a pharmacological study was undertaken."( Pharmacokinetic study in carboplatin, cisplatin and 5-fluorouracil regimen for advanced oesophageal cancer.
Bargnoux, PJ; Cure, H; Leger-Enreille, A; Pezet, D, )		0.13
" The pharmacokinetic profile of 5-FU was characterized for 36 cycles and was compared with the patient's tolerance."( Pharmacodynamics of 5-fluorouracil combined with carboplatin in patients with head and neck cancer.
Klein, T; Leveque, D; Wihlm, J, )		0.13
" Since the toxicities of either drug largely depended upon circadian dosing time, such a pharmacokinetic study was performed following injection of either Pt complex at a time of low (16 h after light onset-HALO), intermediate (0 HALO) or high (8 HALO) toxicity."( Comparative pharmacokinetics of oxaliplatin (L-OHP) and carboplatin (CBDCA) in mice with reference to circadian dosing time.
Boughattas, NA; Bouzouita, K; Bruguerolle, B; Fournier, C; Hecquet, B; Lévi, F; Omrane, B; Trabelsi, H, 1994)		0.29
" In studies described here, we examined the potential of combining IL-1 alpha and the platinum analogue carboplatin (CBDCA) and compared the schedule-dependent and pharmacokinetic effects for IL-1 alpha combinations with cDDP and CBDCA."( Potentiation by interleukin 1 alpha of cisplatin and carboplatin antitumor activity: schedule-dependent and pharmacokinetic effects in the RIF-1 tumor model.
Chang, MJ; Egorin, MJ; Erkmen, K; Furmanski, P; Johnson, CS; Modzelewski, RA; Reyno, LM; Vlock, DR; Yu, WD, 1994)		0.29
" The present study showed that previous carboplatin administrations induced wide variations of melphalan pharmacokinetic parameters between the two administrations."( [Effect of carboplatin on the pharmacokinetics of melphalan administered intravenously].
Ardiet, C; Biron, P; Bouffet, E; Brunat-Mentigny, M; Nasri, F; Philip, I; Tranchand, B, 1994)		0.29
" These pharmacokinetic properties of carboplatin are of advantage in preventing and treating tumor recurrence in the peritoneal cavity and hepatic metastases."( [Experimental pharmacokinetic studies of carboplatin intraperitoneal chemotherapy].
Chen, JQ; Wang, J, 1994)		0.29
" Patient characteristics, drug dose, and pharmacokinetic parameters were examined as predictors of marrow engraftment as reflected by recovery of granulocytes and platelets."( Altered etoposide pharmacokinetics and time to engraftment in pediatric patients undergoing autologous bone marrow transplantation.
Madden, T; Murry, DJ; Rodman, JH; Santana, VM, 1994)		0.29
"The median values for clearance (Cl) and terminal half-life (T1/2 beta) of etoposide were 14."( Altered etoposide pharmacokinetics and time to engraftment in pediatric patients undergoing autologous bone marrow transplantation.
Madden, T; Murry, DJ; Rodman, JH; Santana, VM, 1994)		0.29
" Pharmacokinetic data suggested t1/2 alpha and t1/2 beta for carboplatin were prolonged after pretreatment with etanidazole."( Phase I pharmacokinetic study of the hypoxic cell sensitizer etanidazole with carboplatin and cyclophosphamide in the treatment of advanced ovarian cancer.
Berkowitz, R; Buswell, L; Coleman, CN; Goodman, H; Hurwitz, SJ; Kalish, LA; Kusumoto, T; Muto, M; Shulman, LN; Teicher, B, 1994)		0.29
" Pharmacokinetic studies in animals have demonstrated that it is possible to make analogues that have good oral bioavailability."( Platinum complexes in cancer medicine: pharmacokinetics and pharmacodynamics in relation to toxicity and therapeutic activity.
Calvert, H; Judson, I; van der Vijgh, WJ, 1993)		0.29
"Carboplatin was given as a 24-hour infusion at high doses to pediatric patients with cancer (n = 11) and pharmacokinetic parameters and renal effects were determined."( Pharmacokinetics and acute renal effects of continuously infused carboplatin.
Murry, DJ; Rodman, JH; Sandlund, JT; Stricklin, LM, 1993)		0.29
" Two further equations were developed that use the 51Cr-EDTA half-life (t1/2) to calculate the GFR and these may reduce errors resulting from inaccurate measurement of the volume of distribution for 51Cr-EDTA."( Carboplatin pharmacokinetics in children: the development of a pediatric dosing formula. The United Kingdom Children's Cancer Study Group.
Balmanno, K; Calvert, AH; Keir, M; Lewis, IJ; Newell, DR; Pearson, AD; Pinkerton, CR; Price, L; Stevens, MC; Wyllie, RA, 1993)		0.29
" Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T1/2), area-under-the-curve and total body clearance (CLb) were not dose dependent."( Pharmacokinetic and phase I evaluation of carboplatin in dogs.
Dewhirst, MW; George, SL; Heidner, GL; McEntee, MC; Novotney, CA; Page, RL; Riviere, JE; Thrall, DE; Williams, PL, )		0.13
" The results show that elimination half-life of total platinum was 13 hours in the children with normal renal function and 42 hours in the anephric child following the 100 mg/m2 dose."( Comparison of carboplatin pharmacokinetics between an anephric child and two children with normal renal function.
Klein, J; Koren, G; Moselhy, G; Weitzman, S, 1993)		0.29
" Pharmacokinetic studies were performed at the maximum tolerated dose (MTD)."( A phase I and pharmacokinetic study of intraperitoneal carboplatin and etoposide.
Alcaraz, J; Andrews, P; Braly, P; Goel, R; Gorelick, S; Hoff, S; Kim, S; Kirmani, S; McClay, EF; Plaxe, S, 1993)		0.29
" A population pharmacokinetic study was undertaken to determine a relationship between patient characteristics and carboplatin clearance."( [Prediction of carboplatin clearance from morphological and biological patient characteristics].
Boneu, A; Bugat, R; Canal, P; Chatelut, E; Chevreau, C; Dezeuze, A; Houin, G; Lavit, M; Pujol, A; Roché, H, 1995)		0.29
" Therapy with carboplatin and etoposide is possible in children and adults with renal failure who require dialysis, but in this situation pharmacokinetic monitoring is essential."( Pharmacokinetically guided dosing of carboplatin and etoposide during peritoneal dialysis and haemodialysis.
Boddy, A; English, MW; Lowis, SP; Newell, DR; Pearson, AD; Peng, B; Price, L, 1996)		0.29
" A population pharmacokinetic study using the NONMEM program was undertaken to determine the effects of a variety of covariates on the clearance of ultrafilterable carboplatin."( Population pharmacokinetics of carboplatin in children.
Boddy, AV; Canal, P; Chatelut, E; Dezeuze, A; Lavit, M; Newell, DR; Pearson, AD; Peng, B; Robert, A; Roché, H; Rubie, H, 1996)		0.29
"The pharmacokinetic parameters and maximal tolerated systemic exposure were determined for carboplatin in young children given in combination with cyclophosphamide and etoposide."( Carboplatin pharmacokinetics in young children with brain tumors.
Friedman, HS; Heideman, RL; Murry, DJ; Petros, WP; Rodman, JH; Tonda, ME, 1996)		0.29
" Carboplatin pharmacokinetic parameters were determined after course 1 and then after every third course of therapy."( Carboplatin pharmacokinetics in young children with brain tumors.
Friedman, HS; Heideman, RL; Murry, DJ; Petros, WP; Rodman, JH; Tonda, ME, 1996)		0.29
"Fifty-five chemotherapy-naive patients with NSCLC were entered onto the pharmacokinetic part of a large phase I trial in which P was administered as a 3-hour infusion at dosages of 100 to 250 mg/m2, and C over 30 minutes at dosages of 300 to 400 mg/m2."( Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre.
Bakker, PJ; Beijnen, JH; Bierhorst, FJ; Dalesio, O; Giaccone, G; Huizing, MT; Koolen, MG; Lai, A; Pinedo, HM; Postmus, PE; Rosing, H; ten Bokkel Huinink, WW; van der Vijgh, WJ; van Warmerdam, LJ; van Zandwijk, N; Veenhof, CH; Vermorken, JB, 1997)		0.3
"The aim of this phase I study was to determine the maximum tolerated dose of a 3-h infusion of paclitaxel, combined with carboplatin at a fixed AUC of 7 mg ml-1 min every 4 weeks for up to six cycles and to evaluate any possible pharmacokinetic interaction."( A clinical and pharmacokinetic study of the combination of carboplatin and paclitaxel for epithelial ovarian cancer.
Bailey, NP; Boddy, AV; Calvert, AH; Lind, MJ; Robson, L; Siddiqui, N; Thomas, HD, 1997)		0.3
" Previous pharmacokinetic studies have suggested that the measured area under the plasma carboplatin concentration-time curve is significantly less than that predicted by dosing formulas based on glomerular filtration rates."( A review of the pharmacokinetics and pharmacodynamics of combination carboplatin/paclitaxel.
Calvert, AH, 1997)		0.3
" We performed a pharmacokinetic study of IP CsA followed by a phase I dose-escalation trial of the combination of IP CsA and carboplatin in refractory ovarian cancer patients."( Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine in refractory ovarian cancer patients.
Chambers, JT; Chambers, SK; Davis, CA; Handschumacher, RE; Kohorn, EI; Lorber, MI; Pizzorno, G; Schwartz, PE, 1997)		0.3
" The area under the concentration-time curve (AUC) for CsA and half-life (T1/2) were calculated."( Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine in refractory ovarian cancer patients.
Chambers, JT; Chambers, SK; Davis, CA; Handschumacher, RE; Kohorn, EI; Lorber, MI; Pizzorno, G; Schwartz, PE, 1997)		0.3
" Pharmacokinetic analysis confirmed that at 20 mg CsA/kg, there was an IP fluid-to-blood AUC ratio of 600:1 in favor of peritoneal exposure."( Pharmacokinetic and phase I trial of intraperitoneal carboplatin and cyclosporine in refractory ovarian cancer patients.
Chambers, JT; Chambers, SK; Davis, CA; Handschumacher, RE; Kohorn, EI; Lorber, MI; Pizzorno, G; Schwartz, PE, 1997)		0.3
"The pharmacologic results seem to exclude a pharmacokinetic interaction between CBDCA and DDP and suggest that a dose of CBDCA 2-fold higher than that used in this study associated intrapleurally with 60 mg/m2 DDP could induce an acceptable and predictable myelosuppression."( Carboplatin and cisplatin pharmacokinetics after intrapleural combination treatment in patients with malignant pleural effusion.
Bogliolo, G; Bottino, GB; Castello, G; Cerruti, A; Esposito, M; Lerza, R; Mencoboni, M; Pannacciulli, I; Reggiardo, G; Tolino, G; Vannozzi, MO; Viale, M, 1997)		0.3
" The pharmacokinetic population program NONMEM was used to determine the best value of substitution for weight in the formula."( How to predict carboplatin clearance from standard morphological and biological characteristics in obese patients.
Bénézet, S; Bugat, R; Canal, P; Chatelut, E; Chevreau, C; Guimbaud, R, 1997)		0.3
" Both unbound species have similar pharmacokinetic profiles for the first 12 hours post-dose."( Clinical pharmacokinetics and dose optimisation of carboplatin.
Duffull, SB; Robinson, BA, 1997)		0.3
"Carboplatin clearance depends on the glomerular filtration rate (GFR), and Calvert's formula is frequently used to achieve a target area under the time vs concentration curve (mg ml(-1) min)."( Adjustment of creatinine clearance improves accuracy of Calvert's formula for carboplatin dosing.
Ando, M; Ando, Y; Minami, H; Saka, H; Sakai, S; Shimokata, K, 1997)		0.3
" This study demonstrates that, after cisplatin and carboplatin treatment the drug-target interaction is determined by both pharmacokinetic and, predominantly, cellular factors."( Platinum-DNA adduct formation in leucocytes of children in relation to pharmacokinetics after cisplatin and carboplatin therapy.
Boddy, AV; English, MW; Newell, DR; Pearson, AD; Peng, B; Price, L; Tilby, MJ, 1997)		0.3
"A total of 52 patients with advanced lung cancer were enrolled in this pharmacokinetic study; 37 received standard-dose carboplatin and 25 received low-dose carboplatin."( Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae.
Kunikane, H; Kunitoh, H; Nagatomo, A; Okamoto, H; Watanabe, K, 1998)		0.3
" Compared with a control group of patients who received carboplatin alone, the patients receiving the combination had a longer final half-life of ultrafilterable platinum species [5."( Pharmacokinetics of carboplatin with and without amifostine in patients with solid tumors.
Eeltink, CM; Fichtinger-Schepman, AM; Korst, AE; van der Sterre, ML; van der Vijgh, WJ; Vermorken, JB, 1997)		0.3
" To determine whether a pharmacokinetic interaction was responsible for this observation, the effect of pretreatment with Taxol on the pharmacokinetics of carboplatin was examined in 11 patients."( Evaluation of carboplatin pharmacokinetics in the absence and presence of paclitaxel.
Brennan, JM; Gallo, JM; Hamilton, TC; Johnson, SW; Kilpatrick, D; O'Dwyer, PJ; Obasaju, CK; Ozols, RF; Rogatko, A, 1996)		0.29
" The pharmacokinetic data are consistent with the expected effect of vigorous mixing on the exposed peritoneal surface area."( A pilot phase I trial of continuous hyperthermic peritoneal perfusion with high-dose carboplatin as primary treatment of patients with small-volume residual ovarian cancer.
Alexander, HR; Bartlett, DL; Dedrick, RL; Egorin, MJ; Steller, MA; Trimble, EL; Zuhowski, EG, 1999)		0.3
"To determine the maximum-tolerated dose of paclitaxel with carboplatin with and without filgrastim support in patients with metastatic non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of paclitaxel and carboplatin and correlate these with the pharmacodynamic effects."( Phase I trial, including pharmacokinetic and pharmacodynamic correlations, of combination paclitaxel and carboplatin in patients with metastatic non-small-cell lung cancer.
Aisner, J; Belani, CP; Capozzoli, MJ; Egorin, MJ; Engstrom, C; Erkmen, K; Hiponia, D; Kearns, CM; Ramanathan, RK; Zacharski, D; Zuhowski, EG, 1999)		0.3
"Thirty-six chemotherapy-naive patients with metastatic NSCLC were entered into this phase I dose-escalation and pharmacokinetic study."( Phase I trial, including pharmacokinetic and pharmacodynamic correlations, of combination paclitaxel and carboplatin in patients with metastatic non-small-cell lung cancer.
Aisner, J; Belani, CP; Capozzoli, MJ; Egorin, MJ; Engstrom, C; Erkmen, K; Hiponia, D; Kearns, CM; Ramanathan, RK; Zacharski, D; Zuhowski, EG, 1999)		0.3
" There is no pharmacokinetic interaction between paclitaxel and carboplatin, but there is a pharmacodynamic, platelet-sparing effect on this dose-limiting toxicity of carboplatin."( Phase I trial, including pharmacokinetic and pharmacodynamic correlations, of combination paclitaxel and carboplatin in patients with metastatic non-small-cell lung cancer.
Aisner, J; Belani, CP; Capozzoli, MJ; Egorin, MJ; Engstrom, C; Erkmen, K; Hiponia, D; Kearns, CM; Ramanathan, RK; Zacharski, D; Zuhowski, EG, 1999)		0.3
" VP-16 and CBDCA concentration were measured by HPLC, and the pharmacokinetic parameters of these drugs estimated in CSF and plasma."( Pharmacokinetics of etoposide and carboplatin in cerebrospinal fluid and plasma during hyperosmotic disruption of the blood brain barrier and intraarterial combination chemotherapy.
Abe, T; Hori, S; Kawashima, H; Mori, T; Morikawa, N; Takeyama, M, 1999)		0.3
" Pharmacokinetic measurements were carried out using a previously validated single sample method."( Pharmacokinetically guided dose escalation of carboplatin in epithelial ovarian cancer: effect on drug-plasma AUC and peripheral blood drug-DNA adduct levels.
Baily, N; Calvert, AH; Ghazal-Aswad, S; Lind, M; Newell, DR; Sinha, DP; Tilby, MJ, 1999)		0.3
"In this report, we describe the development and validation of a limited-sampling model for carboplatin from 77 pharmacokinetic curves, when carboplatin is used in combination with paclitaxel."( A limited-sampling model for the pharmacokinetics of carboplatin administered in combination with paclitaxel.
Beijnen, JH; Huizing, MT; Nannan Panday, VR; Schellens, JH; Ten Bokkel Huinink, WW; van Warmerdam, LJ, 1999)		0.3
" Pharmacokinetic parameters for carboplatin were compared with respect to the dose of Cereport and with historical controls."( Pharmacokinetics of carboplatin administered in combination with the bradykinin agonist Cereport (RMP-7) for the treatment of brain tumours.
Bleehen, N; Boddy, AV; Calvert, AH; Ford, J; Lind, MJ; Thomas, HD, 2000)		0.31
"To evaluate the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetic (PK) profile of paclitaxel and carboplatin when administered every 3 weeks with the oral semisynthetic cyclosporine analog valspodar (PSC 833), an inhibitor of P-glycoprotein function."( Phase I dose-finding and pharmacokinetic study of paclitaxel and carboplatin with oral valspodar in patients with advanced solid tumors.
Egorin, MJ; Fracasso, PM; Kerr, I; Litchman, M; Michael, M; Moore, MJ; Oza, AM; Patnaik, A; Rivkin, S; Siu, LL; Warner, E, 2000)		0.31
" Carboplatin is still the only cytotoxic drug for which dose is individualised not according to the body surface area but according to pharmacokinetic parameters."( [Pharmacokinetics and individual dose adjustment of carboplatin].
Bugat, R; Canal, P; Chatelut, E, 2000)		0.31
"The current practice for the dose calculation of most anticancer agents is based on body surface area in m2, although lower interpatient variation in pharmacokinetic parameters has been reported with pharmacokinetically guided administration."( Pharmacokinetically guided administration of chemotherapeutic agents.
Beijnen, JH; Mathôt, RA; Schellens, JH; van den Bongard, HJ, 2000)		0.31
" Pharmacokinetic sampling was performed during the first and the second course, and the samples were analyzed using a validated high-performance liquid chromatographic assay."( Cremophor EL pharmacokinetics in a phase I study of paclitaxel (Taxol) and carboplatin in non-small cell lung cancer patients.
Beijnen, JH; Boschma, MU; Giaccone, G; Huizing, MT; Meerum Terwogt, J; Nannan Panday, VR; Schellens, JH; ten Bokkel Huinink, WW; van Tellingen, O; Veenhof, CH, 2000)		0.31
" A multiple regression analysis was performed for interactions between pharmacokinetic parameters and pretreatment characteristics."( Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve.
Braess, J; Friedrichsen, S; Hiddemann, W; Kaufmann, CC; Kern, W; Schleyer, E, 2001)		0.31
"Pharmacokinetic and pharmacodynamic data were collected in 17 women entered in a phase II trial of sequential HDP, and high-dose melphalan and cyclophosphamide/thiotepa/carboplatin."( The pharmacokinetics and pharmacodynamics of high-dose paclitaxel monotherapy (825 mg/m2 continuous infusion over 24 h) with hematopoietic support in women with metastatic breast cancer.
Balmaceda, CM; Egorin, MJ; Hesdorffer, CS; Huang, M; Kaufman, E; Papadopoulos, KP; Troxel, AB; Vahdat, LT, 2001)		0.31
" The degree of neurotoxicity subsequent to HDP was associated with the degree of baseline neuropathy but was not predictable from pharmacokinetic parameters."( The pharmacokinetics and pharmacodynamics of high-dose paclitaxel monotherapy (825 mg/m2 continuous infusion over 24 h) with hematopoietic support in women with metastatic breast cancer.
Balmaceda, CM; Egorin, MJ; Hesdorffer, CS; Huang, M; Kaufman, E; Papadopoulos, KP; Troxel, AB; Vahdat, LT, 2001)		0.31
" The objective of the study was to compare two specific population pharmacokinetic methodologies, nonlinear mixed-effect model (NONMEM) and non-parametric expectation maximisation (NPEM), when they are applied to sparse carboplatin pharmacokinetic data in order to obtain an individual value for carboplatin clearance by Bayesian estimation."( Comparison of nonlinear mixed-effect and non-parametric expectation maximisation modelling for Bayesian estimation of carboplatin clearance in children.
Bastian, G; Bleyzac, N; Boddy, AV; Canal, P; Chatelut, E; Doz, F; Maire, P; Patoux, A; Rubie, H, 2001)		0.31
"The three platinum derivatives currently available share many pharmacokinetic and pharmacodynamic (PK-PD) properties but present also some distinct characteristics, due to their structural differences."( [Pharmacokinetic properties of platinium derivatives].
Allain, P; Boisdron-Celle, M; Gamelin, E; Lebouil, A, 2001)		0.31
" CBCA Cmax and Cmin in 2-5 days and on day 15 and 29, as well as total plasma platinum on days 2, 3, 4, 5, 29 and 43 were also assayed."( A preliminary pharmacokinetic study of docetaxel, carboplatin and concurrent radiotherapy for regionally advanced squamous cell carcinoma of the head and neck.
Airoldi, M; Bumma, C; Cattel, L; Delprino, L; Recalenda, V; Rocco, F; Tagini, V, 2001)		0.31
"This study was conducted to assess the utility of pharmacokinetic and pharmacodynamic analyses of carboplatin (CBDCA) and paclitaxel (TAX) employed for chemotherapy in ovarian cancer patients."( Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and paclitaxel for patients with ovarian cancer.
Arakawa, A; Kato, N; Nishikawa, H; Suzumori, K, 2001)		0.31
" The pharmacodynamic model, based on myelosuppression, was assessed in terms of concentrations of free platinum (free-Pt) and TAX in blood samples."( Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and paclitaxel for patients with ovarian cancer.
Arakawa, A; Kato, N; Nishikawa, H; Suzumori, K, 2001)		0.31
" A pharmacodynamic model corresponding to the nadirs of leukocytes and neutrophils and to pd-Plt was thus generated."( Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and paclitaxel for patients with ovarian cancer.
Arakawa, A; Kato, N; Nishikawa, H; Suzumori, K, 2001)		0.31
"This pharmacodynamic model may allow the ready prediction, from AUCtax, AUCpt, and the serum albumin value, of the degree of myelosuppression with combined CBDCA and TAX chemotherapy."( Pharmacokinetic and pharmacodynamic analysis of combined chemotherapy with carboplatin and paclitaxel for patients with ovarian cancer.
Arakawa, A; Kato, N; Nishikawa, H; Suzumori, K, 2001)		0.31
" A specific and selective method for the determination of carboplatin in human plasma and its applications to pharmacokinetic investigations is described."( Simple and rapid determination of carboplatin in plasma by high-performance liquid chromatography. Error pattern and application to clinical pharmacokinetic studies.
Aldaz, A; Castellanos, C; Giráldez, J; Zufía, L, 2001)		0.31
"The interaction between etoposide and platinum drugs is small and, given the pharmacokinetic variability seen with etoposide, the clinical impact is unlikely to be significant."( Randomized cross-over clinical trial to study potential pharmacokinetic interactions between cisplatin or carboplatin and etoposide.
Bartelink, I; Boddy, AV; Calvert, AH; Cole, M; Elliott, S; Highley, M; Newell, DR; Nobbs, JR; Porter, DJ; Thomas, HD, 2002)		0.31
" A population pharmacokinetic study was then undertaken to investigate the effect of demographic covariates on unbound and bound carboplatin clearance and volume parameters."( Pharmacokinetic modelling of total and unbound plasma carboplatin--a population study in 75 children.
Bastian, G; Doz, F; Namouni, F; Urien, S, 2002)		0.31
" Since such treatment is relatively toxic, pharmacokinetic characteristics of total and ultrafiltered platinum, representing different species of platinum complexes formed, were investigated in 29 patients in relation to toxicity."( Toxicity of high-dose carboplatin: ultrafiltered and not total plasma pharmacokinetics is of clinical relevance.
Beyer, J; Jaehde, U; Kloft, C; Siegert, W, 2002)		0.31
"The purpose of this study was to develop a population pharmacokinetic model for Cremophor EL used as a formulation vehicle for paclitaxel."( A population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modelling.
Beijnen, JH; Mathôt, RA; Schellens, JH; van den Bongard, HJ; van Tellingen, O, 2002)		0.31
" The nonlinear mixed-effect modelling (NONMEM) program was used for the population pharmacokinetic analysis."( A population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modelling.
Beijnen, JH; Mathôt, RA; Schellens, JH; van den Bongard, HJ; van Tellingen, O, 2002)		0.31
" The following pharmacokinetic parameters were estimated: volume of the central compartment (V1=2."( A population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modelling.
Beijnen, JH; Mathôt, RA; Schellens, JH; van den Bongard, HJ; van Tellingen, O, 2002)		0.31
"The population model was able to adequately describe the pharmacokinetic parameters and influence of covariates on the pharmacokinetics of Cremophor EL."( A population analysis of the pharmacokinetics of Cremophor EL using nonlinear mixed-effect modelling.
Beijnen, JH; Mathôt, RA; Schellens, JH; van den Bongard, HJ; van Tellingen, O, 2002)		0.31
"To determine the recommended dose of paclitaxel in chemotherapy used in combination with carboplatin, and to examine the pharmacokinetic parameters of paclitaxel and carboplatin in Japanese patients with epithelial ovarian cancer."( Clinical trial and pharmacokinetic study of combination paclitaxel and carboplatin in patients with epithelial ovarian cancer.
Fujimoto, S; Hirano, T; Kaneuchi, M; Negishi, H; Nishiya, M; Okamoto, K; Sakuragi, N; Takeda, M; Todo, Y; Yamamoto, R, 2002)		0.31
"Based on the results of this clinical trial and pharmacokinetic study, 175 mg/m(2) of paclitaxel as a 3-h infusion in combination with carboplatin AUC 5 can be considered as the recommended dose for Japanese ovarian cancer patients."( Clinical trial and pharmacokinetic study of combination paclitaxel and carboplatin in patients with epithelial ovarian cancer.
Fujimoto, S; Hirano, T; Kaneuchi, M; Negishi, H; Nishiya, M; Okamoto, K; Sakuragi, N; Takeda, M; Todo, Y; Yamamoto, R, 2002)		0.31
"By means of a nonlinear mixed effect modeling technique, a population pharmacokinetic (PK) model was developed to evaluate the effects of a variety of covariates on clearance and other pharmacokinetic parameters of ultrafilterable carboplatin administered in high-dose combination regimens with peripheral blood stem cell support."( Population pharmacokinetic and limited sampling models for carboplatin administered in high-dose combination regimens with peripheral blood stem cell support.
Gallo, JM; Obasaju, C; Schilder, RJ; Shen, M, 2002)		0.31
" The pharmacodynamic effects of mesna on depleting plasma cysteine, a GSH precursor, were evaluated in 22 patients as part of a Phase I study."( Pharmacokinetics and pharmacodynamics of mesna-mediated plasma cysteine depletion.
Booker, BM; Creaven, P; Pendyala, L; Perez, R; Smith, PF, 2003)		0.32
"The aim of this study was to use pharmacokinetic analysis to investigate the efficacy and toxicity of combined chemotherapy with carboplatin (CBDCA) and etoposide (ETP) in small-cell lung cancer (SCLC) patients with chronic renal failure undergoing hemodialysis (HD)."( Pharmacokinetic analysis of combination chemotherapy with carboplatin and etoposide in small-cell lung cancer patients undergoing hemodialysis.
Gomi, K; Inoue, A; Kikuchi, T; Maemondo, M; Miki, M; Nukiwa, T; Saijo, Y; Sato, T; Suzuki, T, 2004)		0.32
" The pharmacokinetic analysis of CBDCA and ETP was planned for at least the first two courses of the chemotherapy in each patient."( Pharmacokinetic analysis of combination chemotherapy with carboplatin and etoposide in small-cell lung cancer patients undergoing hemodialysis.
Gomi, K; Inoue, A; Kikuchi, T; Maemondo, M; Miki, M; Nukiwa, T; Saijo, Y; Sato, T; Suzuki, T, 2004)		0.32
"057) in prolonged distribution half-life of total platinum was also observed when mesna was present (t(1/2a) 65 +/- 21 min; n = 3) compared to cisplatin without mesna (t(1/2a), 32 +/- 18 min; n = 5)."( Influence of mesna on the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.
Gangopadhyay, SB; Glück, S; Kangarloo, SB; Syme, RM; Wolff, JE, 2004)		0.32
" In 11 patients, pharmacokinetic parameters were evaluated."( Docetaxel, carboplatin and concomitant radiotherapy for unresectable squamous cell carcinoma of the head and neck: pharmacokinetic and clinical data of a phase I-II study.
Airoldi, M; Bumma, C; Cattel, L; Cortesina, G; Danova, M; Gabriele, AM; Giordano, C; Pedani, F; Porta, C; Recalenda, V; Tagini, V, 2004)		0.32
" The use of real-time pharmacokinetic monitoring to guide dosing within a course of carboplatin treatment resulted in exposures within 15% of the target AUC in all patients."( Pharmacokinetically guided dosing of carboplatin in paediatric cancer patients with bilateral nephrectomy.
Boddy, AV; Cole, S; English, MW; Glaser, A; Grundy, RG; Holden, V; Howe, K; Michalski, A; O'Meara, A; Shakespeare, C; Veal, GJ; Waters, F, 2004)		0.32
"Carboplatin pharmacokinetic studies were performed on 21 of 25 children with primary brain tumors who received carboplatin and lobradimil on two consecutive days every 28 days in a phase I dose-escalation trial of lobradimil."( Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors.
Aikin, A; Balis, FM; Egorin, M; Gervais, A; Warren, K, 2004)		0.32
" The degree to which the measured carboplatin AUC exceeded the target AUC appeared to be greater at higher doses of lobradimil, suggesting that the failure of the adaptive dosing method was related to an unexpected pharmacokinetic drug interaction."( Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors.
Aikin, A; Balis, FM; Egorin, M; Gervais, A; Warren, K, 2004)		0.32
" No alterations in the pharmacokinetic disposition of carboplatin were noted."( Clinical and pharmacokinetic study of TNP-470, an angiogenesis inhibitor, in combination with paclitaxel and carboplatin in patients with solid tumors.
Blumenschein, GR; Fossella, FV; Herbst, RS; Lu, C; Madden, T; Meyers, CA; Munden, R; Papadimitrakopoulou, V; Puduvalli, VK; Smythe, LG; Tran, HT; Truong, M; Zinner, R, 2004)		0.32
"A pharmacokinetic study of carboplatin, following a single intravenous (IV) or intraosseus (IO) infusion over 3 min, was performed in six healthy sulphur-crested cockatoos (Cacatua galerita)."( Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested cockatoos (Cacatua galerita).
Bucher, AM; Charles, BG; Filippich, LJ; Sutton, RH, 2004)		0.32
" A noncompartmental pharmacokinetic analysis was performed on the plasma data."( Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested cockatoos (Cacatua galerita).
Bucher, AM; Charles, BG; Filippich, LJ; Sutton, RH, 2004)		0.32
"The mean +/- SD for the Cmax of filterable Pt was 27."( Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested cockatoos (Cacatua galerita).
Bucher, AM; Charles, BG; Filippich, LJ; Sutton, RH, 2004)		0.32
" Despite anatomical, physiological and biochemical differences among animal species, the pharmacokinetic disposition of filterable Pt in the sulphur-crested cockatoo shares some features with the kinetics reported previously in other animals and human beings."( Carboplatin pharmacokinetics following a single-dose infusion in sulphur-crested cockatoos (Cacatua galerita).
Bucher, AM; Charles, BG; Filippich, LJ; Sutton, RH, 2004)		0.32
"Fludarabine, carboplatin, topotecan regimen is a promising treatment based on potential pharmacodynamic interactions, which merits additional study in poor prognosis, acute leukemia patients."( A phase I and pharmacodynamic study of fludarabine, carboplatin, and topotecan in patients with relapsed, refractory, or high-risk acute leukemia.
Cooper, BW; Creger, RJ; Gerson, SL; Gosky, D; Hoppel, CL; Ingalls, ST; Koc, ON; Lazarus, HM; Meyerson, HJ; Nowell, GM; Pearson, G; Radivoyevitch, T; Tilby, MJ; Veal, GJ, 2004)		0.32
" We performed a phase I and pharmacokinetic study of thalidomide with carboplatin in children with refractory solid tumors."( Phase I and pharmacokinetic study of thalidomide with carboplatin in children with cancer.
Aleksic, A; Berg, SL; Blaney, SM; Bomgaars, LR; Chintagumpala, M; Klenke, RA; Kuttesch, JF, 2004)		0.32
" In addition, we have characterized the pharmacokinetic behavior of thalidomide in children."( Phase I and pharmacokinetic study of thalidomide with carboplatin in children with cancer.
Aleksic, A; Berg, SL; Blaney, SM; Bomgaars, LR; Chintagumpala, M; Klenke, RA; Kuttesch, JF, 2004)		0.32
"To characterize the pharmacokinetic disposition of carboplatin and determine whether glomerular filtration rate (GFR) could be used to predict carboplatin clearance and myelotoxic effects in cats with tumors."( Effect of glomerular filtration rate on clearance and myelotoxicity of carboplatin in cats with tumors.
Bailey, DB; Dykes, NL; Erb, HN; Hoopes, PJ; Page, RL; Rassnick, KM, 2004)		0.32
" Plasma platinum concentrations were measured via atomic absorption spectrophotometry, and pharmacokinetic analysis was performed."( Effect of glomerular filtration rate on clearance and myelotoxicity of carboplatin in cats with tumors.
Bailey, DB; Dykes, NL; Erb, HN; Hoopes, PJ; Page, RL; Rassnick, KM, 2004)		0.32
" To that end, a novel method, based on physiologically based hybrid pharmacokinetic models, is presented to predict human tumor drug concentrations."( Pharmacokinetic model-predicted anticancer drug concentrations in human tumors.
Bookman, MA; Gallo, JM; Guo, P; Li, S; Ma, J; Orlansky, A; Pulfer, S; Vicini, P; Zhou, F, 2004)		0.32
" Doses were adapted on day 3 based on pharmacokinetic analyses of cyclophosphamide, 4-hydroxycyclophosphamide, thiotepa, tepa, and carboplatin done on day 1 using a Bayesian algorithm."( Accuracy, feasibility, and clinical impact of prospective Bayesian pharmacokinetically guided dosing of cyclophosphamide, thiotepa, and carboplatin in high-dose chemotherapy.
Beijnen, JH; de Jonge, ME; Huitema, AD; Rodenhuis, S; Tukker, AC; van Dam, SM, 2005)		0.33
"Describe and compare the central nervous system pharmacology of the platinum analogues, cisplatin, carboplatin, and oxaliplatin and develop a pharmacokinetic model to distinguish the disposition of active drug from inert platinum species."( Plasma and cerebrospinal fluid pharmacokinetics of intravenous oxaliplatin, cisplatin, and carboplatin in nonhuman primates.
Balis, FM; Dennie, C; Fox, E; Jacobs, SS; McCully, CL; Morgan, LB, 2005)		0.33
" For oxaliplatin, cisplatin, and carboplatin, the pharmacokinetic model estimated that active drug accounted for 29%, 79%, and 81% of platinum in plasma ultrafiltrate, respectively, and 25%, 89%, and 56% of platinum in CSF, respectively."( Plasma and cerebrospinal fluid pharmacokinetics of intravenous oxaliplatin, cisplatin, and carboplatin in nonhuman primates.
Balis, FM; Dennie, C; Fox, E; Jacobs, SS; McCully, CL; Morgan, LB, 2005)		0.33
" The pharmacokinetic model distinguished between active drug and their inactive (inert) metabolites in plasma and CSF."( Plasma and cerebrospinal fluid pharmacokinetics of intravenous oxaliplatin, cisplatin, and carboplatin in nonhuman primates.
Balis, FM; Dennie, C; Fox, E; Jacobs, SS; McCully, CL; Morgan, LB, 2005)		0.33
"3-18 years) and determine whether any clinical factors affect the pharmacokinetic parameters Additionally, to examine whether a test melphalan dose can predict the pharmacokinetics of a full dose, when there are 5 intervening days of carboplatin therapy."( Melphalan pharmacokinetics in children with malignant disease: influence of body weight, renal function, carboplatin therapy and total body irradiation.
Earl, JW; Montgomery, K; Nath, CE; Shaw, PJ, 2005)		0.33
" Pharmacodynamic correlations were noted between the docetaxel area under the curve and peripheral neuropathy or stomatitis."( Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies.
Barón, AE; Bearman, SI; Cagnoni, PJ; Gustafson, D; Jones, RB; Long, M; Matthes, S; McSweeney, PA; Nieto, Y; Shpall, EJ, 2005)		0.33
" The mechanism of the sequence effects on toxicity and tumor response could not be explained by the pharmacokinetic interactions."( Sequence effect of docetaxel and carboplatin on toxicity, tumor response and pharmacokinetics in non-small-cell lung cancer patients: a phase I study of two sequences.
Ando, M; Ando, Y; Hasegawa, Y; Kuzuya, T; Minami, H; Saka, H; Sakai, S; Shimokata, K; Watanabe, A; Yamamoto, M, 2005)		0.33
" Pharmacokinetic samples were drawn on day 1 of courses 1 (chemotherapy alone) and 2 (chemotherapy+RPI."( Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGFR-1 ribozyme, in combination with carboplatin and paclitaxel in patients with advanced solid tumors.
Aitchison, RD; Basche, ML; Cooper, W; Eckhardt, SG; Holden, SN; Kobayashi, H; Lockridge, JA; O'Bryant, CL; Rothenberg, ML; Sandler, AB; Usman, N; Wolin, M, 2005)		0.33
" For paclitaxel the ratio of the mean Cmax when administered with carboplatin alone versus with carboplatin and RPI."( Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGFR-1 ribozyme, in combination with carboplatin and paclitaxel in patients with advanced solid tumors.
Aitchison, RD; Basche, ML; Cooper, W; Eckhardt, SG; Holden, SN; Kobayashi, H; Lockridge, JA; O'Bryant, CL; Rothenberg, ML; Sandler, AB; Usman, N; Wolin, M, 2005)		0.33
"4610, carboplatin, and paclitaxel can be administered safely in combination without substantial pharmacokinetic interactions."( Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGFR-1 ribozyme, in combination with carboplatin and paclitaxel in patients with advanced solid tumors.
Aitchison, RD; Basche, ML; Cooper, W; Eckhardt, SG; Holden, SN; Kobayashi, H; Lockridge, JA; O'Bryant, CL; Rothenberg, ML; Sandler, AB; Usman, N; Wolin, M, 2005)		0.33
" Plasma concentrations of BAY and VP-16 were measured to investigate pharmacokinetic interactions."( A phase I and pharmacokinetic study of the selective, non-peptidic inhibitor of matrix metalloproteinase BAY 12-9566 in combination with etoposide and carboplatin.
Alberts, SR; Erlichman, C; Furth, A; Lathia, CD; Molina, JR; Reid, JM; Safgren, SL; Sloan, JA, 2005)		0.33
" In the light of the sensitivity of human ovarian tumour cell lines to BGC9331 and non-cross resistance to platinum drugs, we studied the combination BGC9331/carboplatin (BCA) in a phase I (PI) pharmacokinetic (PK) and pharmacodynamic (PD) study in platinum pretreated gynaecological malignancies."( A phase I pharmacokinetic and pharmacodynamic study of BGC9331 and carboplatin in relapsed gynaecological malignancies.
Aherne, W; Bate, S; Benepal, T; Gore, M; Hardcastle, A; Jackman, A; Mitchell, F; Pyle, L; Raynaud, F; Ruddle, R; Simmons, L, 2005)		0.33
" The aim of this study was to develop a population pharmacokinetic model describing the complex pharmacokinetics of CP, 4OHCP, 2DCECP, and PM when CP is administered in a high-dose combination with thiotepa and carboplatin."( Population pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide, 2-dechloroethylcyclophosphamide, and phosphoramide mustard in a high-dose combination with Thiotepa and Carboplatin.
Beijnen, JH; de Jonge, ME; Huitema, AD; Rodenhuis, S; van Dam, SM, 2005)		0.33
"To determine, in peripheral blood monocytes (PBM), whether the enzymatic activities of fructose 1,6-bisphosphatase (FBPase), cytidine deaminase (CDDase) and 24-hydroxylase (CYP24), enzymes regulated by calcitriol are useful pharmacodynamic (PD) measures of calcitriol effects in cancer patients."( Monocyte fructose 1,6-bisphosphatase and cytidine deaminase enzyme activities: potential pharmacodynamic measures of calcitriol effects in cancer patients.
Branch, RA; Johnson, CS; Muindi, JR; Peng, Y; Trump, DL; Wilson, JW, 2007)		0.34
"To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity."( Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors.
Beeram, M; Hamilton, M; Hammond, LA; Hidalgo, M; Kreisberg, JI; Mita, MM; Nadler, P; Patnaik, A; Rowinsky, EK; Schwartz, G; Tolcher, AW; Wolf, J; Wood, D, 2006)		0.33
" There was no evidence of pharmacokinetic interactions between paclitaxel and erlotinib; however, total carboplatin exposure trended higher in the presence of erlotinib."( Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors.
Beeram, M; Hamilton, M; Hammond, LA; Hidalgo, M; Kreisberg, JI; Mita, MM; Nadler, P; Patnaik, A; Rowinsky, EK; Schwartz, G; Tolcher, AW; Wolf, J; Wood, D, 2006)		0.33
" Fifteen patients participated in a pharmacokinetic study investigating the effects of the sequence of infusion."( Phase I and pharmacokinetic trial of carboplatin and albumin-bound paclitaxel, ABI-007 (Abraxane) on three treatment schedules in patients with solid tumors.
Collichio, FA; Dees, EC; Goldberg, RM; Hawkins, MJ; Ivanova, A; Lindley, C; Mu, H; O'Neil, BH; Socinski, MA; Stinchcombe, TE; Walko, CM, 2007)		0.34
" In the present study, we present the results of a pharmacokinetic analysis performed after two consecutive 1-h IP 30 mg/l cisplatin administrations."( Improvement in intraperitoneal intraoperative cisplatin exposure based on pharmacokinetic analysis in patients with ovarian cancer.
Chauffert, B; Combe, M; Delroeux, D; Guardiola, E; Heyd, B; Hoizey, G; Kantelip, JP; Montange, D; Pivot, X; Royer, B, 2008)		0.35
" Vorinostat area under the concentration versus time curve and half-life increased when vorinostat was coadministered with carboplatin and paclitaxel, but vorinostat did not alter paclitaxel pharmacokinetics."( Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies.
Argiris, AE; Belani, CP; Egorin, MJ; Lagattuta, TF; Musguire, LA; Parise, RA; Potter, DM; Ramalingam, SS; Ramananthan, RK; Ramanathan, RK; Stoller, RG; Zwiebel, JA, 2007)		0.34
" The relationships between pharmacokinetic parameters and hematological adverse effects, as well as pharmacological effects, were examined."( Pharmacokinetics and pharmacodynamics of paclitaxel with carboplatin or gemcitabine, and effects of CYP3A5 and MDR1 polymorphisms in patients with urogenital cancers.
Inui, K; Ito, N; Jiko, M; Kamoto, T; Masuda, S; Motohashi, H; Nakamura, E; Ogawa, O; Okuda, M; Sato, E; Segawa, T; Takahashi, K; Yano, I, 2007)		0.34
"To investigate the relationship between peak concentration (Cmax) of gemcitabine at fixed-dose-rate and its hematological toxicity profile in patients with advanced non-small-cell lung cancer (NSCLC)."( [Peak concentration of gemcitabine at fixed-dose-rate and its hematological toxicity profile].
Huang, MZ; Wang, LR; Zhang, GB, 2007)		0.34
"The mean value of Cmax in 21 eligible patients was(4."( [Peak concentration of gemcitabine at fixed-dose-rate and its hematological toxicity profile].
Huang, MZ; Wang, LR; Zhang, GB, 2007)		0.34
"The results of relationship between Cmax and toxicity profile suggest that gemcitabine administration should be individualized in order to decrease the occurrence of ADR."( [Peak concentration of gemcitabine at fixed-dose-rate and its hematological toxicity profile].
Huang, MZ; Wang, LR; Zhang, GB, 2007)		0.34
" The objective of this study was to develop a pharmacodynamic (PD) model to describe chemotherapy-induced anemia in rats."( Pharmacodynamic model for chemotherapy-induced anemia in rats.
Jusko, WJ; Krzyzanski, W; Woo, S, 2008)		0.35
"From 2002 to 2007, a total of 10 consecutive patients with Stage IVA HCC accompanied by PVTT were studied prospectively to examine the efficacy of treatment by intra-arterial infusion of a chemotherapeutic agents consisting of etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil."( Improved survival for hepatocellular carcinoma with portal vein tumor thrombosis treated by intra-arterial chemotherapy combining etoposide, carboplatin, epirubicin and pharmacokinetic modulating chemotherapy by 5-FU and enteric-coated tegafur/uracil: a p
Imai, M; Ishikawa, T; Kamimura, H; Kamimura, T; Ohta, H; Seki, K; Togashi, T; Tsuchiya, A; Watanabe, K; Yoshida, T, 2007)		0.34
" Pharmacodynamic analyses included 5-methyl-2'-deoxycytidine levels, MAGE1A CpG island methylation, and fetal hemoglobin (HbF) expression."( Phase I and pharmacodynamic trial of the DNA methyltransferase inhibitor decitabine and carboplatin in solid tumors.
Appleton, K; Barrett, S; Bellenger, K; Brown, R; Jadayel, D; Judson, I; Kaye, SB; Lee, C; Mackay, HJ; Mackay, L; McCormick, C; Plumb, JA; Reade, S; Schätzlein, A; Setanoians, A; Strathdee, G; Tang, A; Twelves, C, 2007)		0.34
"One hundred five patients had complete pharmacokinetic and toxicity data."( Population pharmacokinetics and pharmacodynamics of paclitaxel and carboplatin in ovarian cancer patients: a study by the European organization for research and treatment of cancer-pharmacology and molecular mechanisms group and new drug development group
Beijnen, JH; Boddy, AV; Briasoulis, E; Calvert, H; Chatelut, E; Dittrich, C; Féty, R; Hempel, G; Hollema, H; Huitema, AD; Izquierdo, MA; Jodrell, DI; Joerger, M; Karlsson, M; Martoni, A; Pavlidis, N; Richel, DJ; Schellens, JH; Schrijvers, AH; Sleeboom, HP; Sorio, R; Strocchi, E; Tranchand, B; Twelves, C; Van der Vijgh, WJ; Vermorken, JB; Wilkins, J, 2007)		0.34
" The purpose was to compare the two pharmacokinetic model structures when only total paclitaxel concentrations are available."( Comparison of two types of population pharmacokinetic model structures of paclitaxel.
Fransson, M; Gréen, H, 2008)		0.35
"During the first, second and ninth cycle of treatment, blood, urine and CAPD samples were collected for pharmacokinetic analysis of paclitaxel and total and unbound carboplatin-derived platinum."( Continuous ambulatory peritoneal dialysis: pharmacokinetics and clinical outcome of paclitaxel and carboplatin treatment.
de Bruijn, P; Fieren, MW; Heijns, JB; Loos, WJ; van der Burg, ME; van der Gaast, A; van Gelder, T, 2008)		0.35
" Paclitaxel clearance decreased during cycle 2, but no other significant pharmacokinetic interactions were observed."( Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institut
Arnold, A; Chen, E; Ellis, PM; Gauthier, I; Goss, G; Laurie, SA; Powers, J; Puchalski, TA; Robertson, J; Seymour, L; Shepherd, FA; Tu, D; Walsh, W, 2008)		0.35
"To investigate the prognostic value of systemic exposure to etoposide (Area Under the concentration Curve (AUC(VP16))) on overall survival (OS) in patients with small cell lung cancer (SCLC)."( Etoposide pharmacokinetics and survival in patients with small cell lung cancer: a multicentre study.
Chabaud, S; Court-Fortune, I; Falandry, C; Fournel, C; Freyer, G; Girard, P; Ribba, B; Souquet, PJ; Tod, M; Tranchand, B; Trillet-Lenoir, V; You, B, 2008)		0.35
" The pharmacokinetic interactions between G3139 and carboplatin/paclitaxel were measured."( A phase I pharmacokinetic and pharmacodynamic correlative study of the antisense Bcl-2 oligonucleotide g3139, in combination with carboplatin and paclitaxel, in patients with advanced solid tumors.
Alberti, D; Eickhoff, J; Kolesar, J; Lee, F; Leith, C; Liu, G; Marnocha, R; McNeel, DG; Schell, K; Traynor, A; Wilding, G; Zwiebel, J, 2008)		0.35
"This tumor response pharmacodynamic model aims to describe primary lesion shrinkage in non-small cell lung cancer over time and determine if concentration-based exposure metrics for gemcitabine or that of its metabolites, 2',2'-difluorodeoxyuridine or gemcitabine triphosphate, are better than gemcitabine dose for prediction of individual response."( A pharmacodynamic model for the time course of tumor shrinkage by gemcitabine + carboplatin in non-small cell lung cancer patients.
Goh, BC; Holford, NH; Lee, HS; Lee, SC; Soo, RA; Tham, LS; Wang, L; Yong, WP, 2008)		0.35
" Pharmacokinetic data were analysed with nonlinear mixed effects modelling."( Population pharmacokinetic and pharmacodynamic analysis to support treatment optimization of combination chemotherapy with indisulam and carboplatin.
Beijnen, JH; Dittrich, C; Huitema, AD; Schellens, JH; Wanders, J; Zandvliet, AS, 2008)		0.35
" Relations between allelic variants and elimination pharmacokinetic parameters were evaluated using nonlinear mixed effects modelling (nonmem)."( Polymorphisms of drug-metabolizing enzymes (GST, CYP2B6 and CYP3A) affect the pharmacokinetics of thiotepa and tepa.
Beijnen, JH; Doodeman, VD; Ekhart, C; Huitema, AD; Rodenhuis, S; Smits, PH, 2009)		0.35
" Blood was sampled during cycle 1 for pharmacokinetic analysis of ixabepilone (both schedules) and carboplatin (schedule B)."( A phase I and pharmacokinetic study of ixabepilone in combination with Carboplatin in patients with advanced solid malignancies.
Boddy, AV; Carmichael, J; Cohen, M; Fyfe, D; Griffin, M; Hewitt, P; Namouni, F; Plummer, R; Verrill, M; Woll, P, 2008)		0.35
" Ixabepilone and carboplatin pharmacokinetics were similar to those using either drug as monotherapy, indicating an absence of pharmacokinetic drug interactions."( A phase I and pharmacokinetic study of ixabepilone in combination with Carboplatin in patients with advanced solid malignancies.
Boddy, AV; Carmichael, J; Cohen, M; Fyfe, D; Griffin, M; Hewitt, P; Namouni, F; Plummer, R; Verrill, M; Woll, P, 2008)		0.35
"The aim of this study was to investigate the safety, pharmacokinetic and pharmacodynamic profiles of pegfilgrastim (KRN125), a long-acting granulocyte colony-stimulating factor, in lung cancer patients with chemotherapy-induced neutropenia."( A pharmacokinetic and dose escalation study of pegfilgrastim (KRN125) in lung cancer patients with chemotherapy-induced neutropenia.
Fukuoka, M; Nakagawa, K; Saijo, N; Sekine, I; Takada, M; Tanigawara, Y; Yamamoto, N, 2009)		0.35
" Pharmacokinetic, pharmacodynamic and safety analyses were performed."( A pharmacokinetic and dose escalation study of pegfilgrastim (KRN125) in lung cancer patients with chemotherapy-induced neutropenia.
Fukuoka, M; Nakagawa, K; Saijo, N; Sekine, I; Takada, M; Tanigawara, Y; Yamamoto, N, 2009)		0.35
" Severe neutropenia (G3 and G4) was seen in seven patients associated with greater AUC, peak concentration (C(max)) and the duration of plasma concentration >50 ng/ml of paclitaxel."( Dose-escalating and pharmacokinetic study of a weekly combination of paclitaxel and carboplatin for inoperable non-small cell lung cancer: JCOG 9910-DI.
Fujii, T; Hida, N; Kunikane, H; Naoki, K; Okamoto, H; Tsujimura, S; Watanabe, K, 2009)		0.35
" Other pharmacodynamic factors than the ones investigated must explain the schedule-dependent differences in toxicities."( Phase I pharmacokinetic and pharmacodynamic study of Carboplatin and topotecan administered intravenously every 28 days to patients with malignant solid tumors.
Beijnen, JH; Boss, DS; Pluim, D; Rosing, H; Schellens, JH; Siegel-Lakhai, WS; Ten Bokkel Huinink, WW; van Egmond-Schoemaker, NE, 2009)		0.35
" There are no apparent pharmacokinetic interactions among the drugs."( Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study.
Camidge, DR; Chow, LQ; Cohen, RB; Diab, S; Eckhardt, SG; Fox, NL; Gore, L; Gustafson, DL; Hariharan, S; Langer, CJ; Leong, S; Miceli, R; O'Bryant, C; Padavic, K; Smith, M; von Mehren, M, 2009)		0.35
" The peak concentration of platinum in plasma was significantly higher in group A compared to those of the other 2 administration routes (P < ."( Pharmacokinetic comparison between systemic and local chemotherapy by carboplatin in dogs.
Chen, C; Huang, J; Liu, P; Song, T; Sun, M; Wang, W; Zhou, H, 2009)		0.35
" Pharmacokinetic analysis was carried out using a non-linear mixed effects modelling approach."( Pharmacokinetics of carboplatin and etoposide in infant neuroblastoma patients.
Boddy, AV; Cole, M; Ellershaw, C; Errington, J; Gerrard, M; Pearson, AD; Veal, GJ; Whyman, G, 2010)		0.36
" Etoposide pharmacokinetic data support previous findings that question the utility of modified dosing in infants."( Pharmacokinetics of carboplatin and etoposide in infant neuroblastoma patients.
Boddy, AV; Cole, M; Ellershaw, C; Errington, J; Gerrard, M; Pearson, AD; Veal, GJ; Whyman, G, 2010)		0.36
" Safety, efficacy, pharmacokinetic, and pharmacodynamic endpoints were investigated."( Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel and carboplatin.
Cardenal, F; Cohen, RB; Demers, L; Eisenberg, PD; Garland, L; Gualberto, A; Haluska, P; Hixon, ML; Karp, DD; Langer, CJ; Leitzel, K; Lipton, A; Paz-Ares, LG; Pollak, MN; Terstappen, LW; Yin, D, 2009)		0.35
" Based on its favorable safety, pharmacokinetic, and pharmacodynamic properties, the maximal feasible dose of 20 mg/kg has been selected for further investigation."( Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel and carboplatin.
Cardenal, F; Cohen, RB; Demers, L; Eisenberg, PD; Garland, L; Gualberto, A; Haluska, P; Hixon, ML; Karp, DD; Langer, CJ; Leitzel, K; Lipton, A; Paz-Ares, LG; Pollak, MN; Terstappen, LW; Yin, D, 2009)		0.35
" The results of this study also showed that this combination therapy had encouraging antitumor activity and was not associated with relevant pharmacokinetic interaction in Japanese NSCLC patients."( Phase I clinical and pharmacokinetic study of sorafenib in combination with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Fukino, K; Fukuoka, M; Hasegawa, Y; Kaneda, H; Kawada, A; Miyazaki, M; Morinaga, R; Nakagawa, K; Okamoto, I; Satoh, T; Tanigawa, T; Ueda, S, 2010)		0.36
" Pharmacokinetic analysis showed we had achieved the desired serum concentration of paclitaxel."( Pharmacokinetics of paclitaxel and carboplatin in a hemodialysis patient with advanced ovarian cancer.
Abe, K; Ishiko, O; Sumi, T; Yoshida, H, 2009)		0.35
" To determine possible drug-drug interaction with this combination, a subset of 24 (12 erlotinib, 12 placebo) patients were enrolled onto an intensive pharmacokinetic (IPK) substudy group at a single site."( Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC).
Blumenschein, GR; Herbst, RS; Kim, ES; Lu, C; Lum, BL; Malik, M; Oh, YW; Papadimitrakopoulou, VA; Tran, HT; Zinner, RG, 2011)		0.37
"Complete blood sampling for pharmacokinetic analysis was obtained in 21 of 24 patients."( Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC).
Blumenschein, GR; Herbst, RS; Kim, ES; Lu, C; Lum, BL; Malik, M; Oh, YW; Papadimitrakopoulou, VA; Tran, HT; Zinner, RG, 2011)		0.37
"A combined data set with 69 patients from five studies, including 13 pediatric patients, was subject to a population pharmacokinetic analysis using NONMEM."( Population pharmacokinetics of high-dose carboplatin in children and adults.
Eickhoff, C; Jaehde, U; Kloft, C; Lindauer, A, 2010)		0.36
"The two population pharmacokinetic models presented can be applied to estimate individual carboplatin clearance in high-dose chemotherapy based on body weight or height, infusion duration, and creatinine clearance."( Population pharmacokinetics of high-dose carboplatin in children and adults.
Eickhoff, C; Jaehde, U; Kloft, C; Lindauer, A, 2010)		0.36
"The combination was well tolerated, with no evidence of pharmacokinetic interaction."( A phase I study of the safety and pharmacokinetics of the histone deacetylase inhibitor belinostat administered in combination with carboplatin and/or paclitaxel in patients with solid tumours.
Buhl-Jensen, P; Crowley, E; de Bono, JS; Engelholm, SA; Knoblauch, P; Lassen, U; Molife, LR; Penson, RT; Sinha, R; Sorensen, M; Tjornelund, J; Vidal, L, 2010)		0.36
"Intraindividual comparative pharmacokinetic data were obtained for doxorubicin and paclitaxel/platinum in three and two baboons, respectively."( Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study.
Amant, F; Chai, D; de Bruijn, E; de Hoon, J; Delforge, M; Halaska, M; Heyns, L; Noens, L; Ottevanger, N; Renard, V; Rob, L; Van Bree, R; Van Calsteren, K; Verbesselt, R; Witteveen, E, 2010)		0.36
" Pharmacokinetic (PK) sampling was performed in the first 2 cycles."( Phase I clinical and pharmacokinetic study of trabectedin and carboplatin in patients with advanced solid tumors.
Barlow, C; Florez, A; Garcia, M; Judson, I; Kaye, SB; Lebedinsky, C; Magem, M; Montes, A; Pardo, B; Salazar, R; Vidal, L, 2012)		0.38
" This combination therapy also showed promising antitumor activity and was not associated with relevant pharmacokinetic interactions."( Safety and pharmacokinetic study of nab-paclitaxel plus carboplatin in chemotherapy-naïve patients with advanced non-small cell lung cancer.
Kubota, K; Murakami, H; Nakagawa, K; Nogami, N; Ohe, Y; Okamoto, I; Ono, K; Yamamoto, N; Yamaya, H, 2012)		0.38
" Pharmacokinetic parameters were estimated using non-compartmental analyses."( The plasma and cerebrospinal fluid pharmacokinetics of the platinum analog satraplatin after intravenous administration in non-human primates.
Balis, FM; Cruz, R; Fox, E; Marcus, L; McCully, C; McNiff, E; Meyer, T; Murphy, R; Warren, KE; Widemann, BC, 2012)		0.38
"To evaluate the ability of a physiology-based pharmacokinetic (PBPK) model to predict the systemic drug exposure of high- and low-dose etoposide in children from a model developed with adult data."( Physiologically based pharmacokinetic modelling of high- and low-dose etoposide: from adults to children.
Boos, J; Hempel, G; Kersting, G; Lippert, J; Willmann, S; Würthwein, G, 2012)		0.38
" This approach could be useful for planning pharmacokinetic studies in children."( Physiologically based pharmacokinetic modelling of high- and low-dose etoposide: from adults to children.
Boos, J; Hempel, G; Kersting, G; Lippert, J; Willmann, S; Würthwein, G, 2012)		0.38
" The primary objective of this study was to determine whether repeated doses of bexarotene capsules affect pharmacokinetic parameters of paclitaxel or carboplatin in patients with advanced non-small cell lung cancer."( A phase I pharmacokinetic study of bexarotene with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC).
Chu, Q; Jacobs, CD; Lopez-Anaya, A; Rodon, J; Rowinsky, EK; Takimoto, CH; Wakelee, HA, 2012)		0.38
" Blood sampling to characterize the pharmacokinetic profiles of the chemotherapeutic agents with or without bexarotene was performed during cycle 1 (without concomitant bexarotene) and during cycle 2 (with concomitant bexarotene)."( A phase I pharmacokinetic study of bexarotene with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC).
Chu, Q; Jacobs, CD; Lopez-Anaya, A; Rodon, J; Rowinsky, EK; Takimoto, CH; Wakelee, HA, 2012)		0.38
" The aim of the present study was to evaluate the pharmacokinetic characteristics of platinum originating from dicycloplatin."( Pharmacokinetics, tissue distribution, and plasma protein binding study of platinum originating from dicycloplatin, a novel antitumor supramolecule, in rats and dogs by ICP-MS.
Chen, X; Dong, C; Han, D; Li, C; Lin, H; Ren, S; Wang, X; Xu, C; Yang, S; Zhang, L; Zhang, Y; Zhao, D, 2012)		0.38
"This phase I and pharmacokinetic study was designed to determine the maximum tolerated dose and to establish the RD of VFL in combination with carboplatin."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012)		0.38
" Pharmacokinetic analysis was performed in 26 patients to determine the total and ultrafiltered platinum concentrations in plasma."( Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results.
Guan, ZZ; Guo, Y; Huang, H; Jiang, WQ; Li, S; Liao, H; Yang, XQ; Zhan, J; Zou, BY, 2013)		0.39
" The terminal plasma half-life of total platinum after DCP administration ranged from 41."( Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results.
Guan, ZZ; Guo, Y; Huang, H; Jiang, WQ; Li, S; Liao, H; Yang, XQ; Zhan, J; Zou, BY, 2013)		0.39
" The present method was applied to a clinical pharmacokinetic study of carboplatin in a cancer patient."( Quantification of intact carboplatin in human plasma ultrafitrates using hydrophilic interaction liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.
Fujikawa, A; Iseki, K; Ito, H; Kobayashi, M; Mano, N; Ogura, J; Shiida, N; Tanaka, N; Yamada, T; Yamaguchi, H, 2013)		0.39
" Pharmacodynamic activity of A(1-7) in platelet production and retention of scheduled dose intensity were also determined."( Pharmacodynamic stimulation of thrombogenesis by angiotensin (1-7) in recurrent ovarian cancer patients receiving gemcitabine and platinum-based chemotherapy.
Cruickshank, S; Delmore, JE; diZerega, GS; Drummond, L; Peterson, KJ; Pham, H; Reed, E; Rodgers, KE; Schwartz, BM, 2013)		0.39
"A 100 mcg/kg dose of A(1-7) was shown to produce pharmacodynamic effects on peripheral blood platelet counts, preserve planned dose intensity, and reduce Grade 3-4 thrombocytopenia following gemcitabine and platinum chemotherapy."( Pharmacodynamic stimulation of thrombogenesis by angiotensin (1-7) in recurrent ovarian cancer patients receiving gemcitabine and platinum-based chemotherapy.
Cruickshank, S; Delmore, JE; diZerega, GS; Drummond, L; Peterson, KJ; Pham, H; Reed, E; Rodgers, KE; Schwartz, BM, 2013)		0.39
"This phase I study of fixed dose rate (FDR) gemcitabine and carboplatin assessed the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), safety, pharmacokinetic (PK)/pharmacodynamic (PD) profile and preliminary anti-tumor activity in patients with recurrent ovarian cancer (OC)."( Phase I dose-escalation study and population pharmacokinetic analysis of fixed dose rate gemcitabine plus carboplatin as second-line therapy in patients with ovarian cancer.
Beijnen, JH; Huitema, AD; Leijen, S; Schellens, JH; van Werkhoven, E; Veltkamp, SA, 2013)		0.39
" Population pharmacokinetic modeling and simulation were performed to further investigate the optimal schedule."( Phase I dose-escalation study and population pharmacokinetic analysis of fixed dose rate gemcitabine plus carboplatin as second-line therapy in patients with ovarian cancer.
Beijnen, JH; Huitema, AD; Leijen, S; Schellens, JH; van Werkhoven, E; Veltkamp, SA, 2013)		0.39
" This Perspective discusses the use of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) for pharmacodynamic evaluation in a very early phase of treatment to predict clinical outcomes in patients with advanced non-small-cell lung cancer."( Early pharmacodynamic assessment using ¹⁸F-fluorodeoxyglucose positron-emission tomography on molecular targeted therapy and cytotoxic chemotherapy for clinical outcome prediction.
Ando, M; Asami, K; Atagi, S; Ishii, M; Kanazu, M; Kawaguchi, T; Kubo, A; Kusunoki, Y; Maruyama, K; Matsuda, Y; Minomo, S; Ogawa, Y; Takada, M; Uehira, K, 2014)		0.4
" Primary endpoints assessed the safety and pharmacokinetic (PK) interactions between navitoclax in combination with carboplatin/paclitaxel or paclitaxel alone in patients with solid tumors The study comprised two arms, one a combination of navitoclax with paclitaxel and carboplatin, the second with navitoclax and paclitaxel alone."( A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors.
Busman, T; Cosgrove, D; Karantza, V; Mabry, M; Rudersdorf, N; Vlahovic, G; Wang, D; Xiong, H; Yang, J, 2014)		0.4
" Ombrabulin clearance was high with a short terminal half-life and a medium volume of distribution."( Phase I clinical and pharmacokinetic study of ombrabulin (AVE8062) combined with cisplatin/docetaxel or carboplatin/paclitaxel in patients with advanced solid tumors.
Bahleda, R; Capri, G; Daglish, B; Del Conte, G; Gianni, L; Hospitel, M; Oprea, C; Sessa, C; Soria, JC; Varga, A, 2014)		0.4
" The pharmacokinetic study showed a significant inverse correlation between the AUC of pemetrexed and the creatinine clearance."( Dose escalation and pharmacokinetic study of carboplatin plus pemetrexed for elderly patients with advanced nonsquamous non-small-cell lung cancer: Kumamoto thoracic oncology study group trial 1002.
Akaike, K; Fujii, S; Hamada, A; Hirosako, S; Iriki, T; Kishi, H; Kohrogi, H; Nakamura, K; Notsute, D; Saeki, S; Sakata, S; Saruwatari, K; Sasaki, J; Sato, R; Tanaka, H, 2015)		0.42
"The objective of this study was to evaluate the potential for a pharmacokinetic (PK) drug-drug interaction (DDI) between trastuzumab and carboplatin and to evaluate the potential effect of trastuzumab on the electrocardiogram QT interval."( Lack of a pharmacokinetic interaction between trastuzumab and carboplatin in the presence of docetaxel: results from a phase Ib study in patients with HER2-positive metastatic or locally advanced inoperable solid tumors.
Eppler, S; Gordon, MS; Han, K; Lum, BL; Redfern, CH; Trudeau, C; Xu, N, 2015)		0.42
" As we had a chance to treat a one-year-old anuric hepatoblastoma patient with carboplatin, we performed a pharmacokinetic analysis and examined the optimal treatment strategy."( Pharmacokinetics of Carboplatin in a One-Year-Old Anuric Boy Undergoing Hemodialysis and a Review of the Literature.
Ishikawa, T; Ito, S; Kamei, K; Kiyotani, C; Mori, T; Nakamura, H; Ogura, M; Sako, M; Sato, M; Tanaka, H; Uno, T, 2015)		0.42
" Despite this, literature reports regarding dosing strategies and pharmacokinetic behaviour of chemotherapeutics in avian species are lacking."( Comparative Pharmacokinetics and Allometric Scaling of Carboplatin in Different Avian Species.
Antonissen, G; Croubels, S; De Backer, P; De Baere, S; Devreese, M; Hellebuyck, T; Martel, A; Rouffaer, L; Stemkens, HJ; Van de Maele, I, 2015)		0.42
" The pharmacodynamic model consisted of a series of aging compartments representing proliferating megakaryocyte precursors, megakaryocytes, and platelets with possible eTPO clearance through internalization."( Pharmacodynamic model for chemoradiotherapy-induced thrombocytopenia in mice.
Harrold, J; Krzyzanski, W; Perez-Ruixo, JJ, 2015)		0.42
"A method for Bayesian prediction of myelosuppression profiles during chemotherapy using a population pharmacodynamic model is proposed, and predictabilities of nadir values and times to nadir (Tnadir) after gemcitabine and carboplatin treatment were evaluated."( Population Pharmacodynamic Model for Bayesian Prediction of Myelosuppression Profiles Based on Routine Clinical Data after Gemcitabine and Carboplatin Treatment.
Chisaki, Y; Terada, T; Yano, Y, 2016)		0.43
"To further explore this drug interaction, a population pharmacokinetic (PK) model was designed that included a lag time parameter, a second absorption compartment from tablet formulation, a single distribution/elimination compartment, and covariance among the clearance and volume parameters."( Population pharmacokinetic analyses of the effect of carboplatin pretreatment on olaparib in recurrent or refractory women's cancers.
Annunziata, CM; Figg, WD; Kohn, EC; Lee, JM; Minasian, L; Nguyen, J; Peer, CJ; Rodgers, L; Roth, J, 2017)		0.46
" Total plasma platinum AUC and Cmax were 9,165."( Pharmacokinetics and toxicity of subcutaneous administration of carboplatin in poloxamer 407 in a rodent model pilot study.
Davidson, G; Griffith, E; Linder, KE; Messenger, KM; Risselada, M; Roberts, BV; Zamboni, WC, 2017)		0.46
"Using pharmacokinetic parameters obtained from 385 drug administrations in 352 children aged from 1 month to 18 years, treated with five drugs (dactinomycin, busulfan, carboplatin, cyclophosphamide and etoposide), individual exposures (area under the plasma drug concentration versus time curve; AUC) obtained using doses rounded according to the published NHSE tables were calculated and compared with those obtained by standard dose calculation methods."( Investigating the potential impact of dose banding for systemic anti-cancer therapy in the paediatric setting based on pharmacokinetic evidence.
Boddy, AV; Chatelut, E; Osborne, C; Paci, A; Veal, GJ; White-Koning, M, 2018)		0.48
"Based on pharmacokinetic data for these five drugs, the results generated support the implementation of NHSE dose-banding tables."( Investigating the potential impact of dose banding for systemic anti-cancer therapy in the paediatric setting based on pharmacokinetic evidence.
Boddy, AV; Chatelut, E; Osborne, C; Paci, A; Veal, GJ; White-Koning, M, 2018)		0.48
" A population pharmacokinetic model was built for carboplatin to evaluate various dosing formulas."( Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Boddy, AV; Duong, JK; Errington, J; Ladenstein, R; Nath, CE; Shaw, PJ; Veal, GJ, 2019)		0.51
"Allometric weight was the only significant, independent covariate for the pharmacokinetic parameters of carboplatin, etoposide and melphalan."( Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Boddy, AV; Duong, JK; Errington, J; Ladenstein, R; Nath, CE; Shaw, PJ; Veal, GJ, 2019)		0.51
"GFR did not appear to influence the pharmacokinetics of carboplatin after adjusting pharmacokinetic parameters for weight."( Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Boddy, AV; Duong, JK; Errington, J; Ladenstein, R; Nath, CE; Shaw, PJ; Veal, GJ, 2019)		0.51
" PK-model-only approach: a 3-compartment pharmacokinetic (PK) model based on U and P concentrations and taking into account the protein binding process was developed."( Estimation of Unbound Carboplatin Clearance From Total Plasma Concentrations as a Means of Facilitating Therapeutic Drug Monitoring.
Bay, JO; Chatelut, E; Chevreau, C; Ciccolini, J; Delahousse, J; Delva, R; Filleron, T; Fléchon, A; Gladieff, L; Gravis, G; Gross-Goupil, M; Guitton, J; Lelièvre, B; Lochon, I; Lotz, JP; Massart, C; Moeung, S; Poinsignon, V; Thomas, F, 2019)		0.51
" This case focuses on using pharmacokinetic (PK) guided chemotherapy to treat neonatal neuroblastoma."( The use of pharmacokinetically guided carboplatin chemotherapy in a pre-term infant with neuroblastoma-associated spinal cord compression.
Errington, J; Hawley, J; McDonald, LG; Tweddle, DA; Veal, GJ, 2019)		0.51
" To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol."( Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.
Beumer, JH; Christner, S; Chu, E; Guo, J; Holleran, JL; Ivy, SP; Joshi, A; Kiesel, B; Miller, BM; Parise, RA; Taylor, S; Venkataramanan, R, 2020)		0.56
" Measuring GFR with iohexol to better dose carboplatin is unlikely to alter the safety or efficacy of chemotherapy through pharmacokinetic drug-drug interactions."( Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.
Beumer, JH; Christner, S; Chu, E; Guo, J; Holleran, JL; Ivy, SP; Joshi, A; Kiesel, B; Miller, BM; Parise, RA; Taylor, S; Venkataramanan, R, 2020)		0.56
" The difference between CRAFT- and CG-based CRCL was assessed by population pharmacokinetic modelling."( Optimizing carboplatin dosing by an improved prediction of carboplatin clearance using a CT-enhanced estimate of renal function.
Beijnen, JH; Dorlo, TPC; Huitema, ADR; Moeskops, P; Molenaar-Kuijsten, L; Pieters, TT; Rijkhorst, EJ; Rookmaaker, MB; Steeghs, N; Veldhuis, WB, 2023)		0.91

Compound-Compound Interactions

The study evaluated the safety, maximum tolerated dose, pharmacokinetics, and antitumor activity of sorafenib, a multikinase inhibitor, combined with paclitaxel and carboplatin in patients with solid tumors.

ExcerptReferenceRelevance
" Radiotherapy is often combined with concurrent chemotherapy although no firm evidence exists that such combinations are more effective than radiotherapy alone."( Induction chemotherapy with carboplatin and 5-fluorouracil in combination with radiotherapy in loco-regionally advanced epidermoid carcinoma of the anus--preliminary results.
Goldman, S; Kaigas, M; Svensson, C, 1992)		0.28
"The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients."( [The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients].
Fujiwara, K; Kohno, I; Koike, H; Mohri, H; Ohishi, Y; Sawada, S; Yamauchi, H, 1992)		0.28
" All 40 courses were administered with a daily 4-hour intravenous (IV) infusion of either 5 or 10 micrograms/kg/d of recombinant human Escherichia coli-derived GM-CSF."( Sequential cycles of high-dose carboplatin administered with recombinant human granulocyte-macrophage colony-stimulating factor and repeated infusions of autologous peripheral-blood progenitor cells: a novel and effective method for delivering multiple co
Breslin, M; Christian, M; Mason, JR; Miller, L; Mullen, M; Newton, B; Shea, TC; Storniolo, AM; Taetle, R; Ward, DM, 1992)		0.28
"A study was undertaken to examine the relationships between carboplatin's pharmacokinetic parameters and the myelotoxicity associated with its administration in combination with cyclophosphamide."( Dose-toxicity relationship of carboplatin in combination with cyclophosphamide in ovarian cancer patients.
Jakobsen, A; Jakobsen, P; Strömgren, A; Sørensen, BT, 1991)		0.28
"The antitumor activity and normal tissue toxicity of cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) in combination with whole body hyperthermia (WBH) (41."( Effect of carboplatin combined with whole body hyperthermia on normal tissue and tumor in rats.
Baba, H; Bull, JM; Khokhar, AR; Ohno, S; Siddik, ZH; Stephens, LC; Strebel, FR; Wondergem, J, 1991)		0.28
"In two separate studies of patients with ovarian cancer, subjects were treated on a protocol comprising 400 mg/m2 carboplatin in combination with 1 g/m2 cyclophosphamide (group A) or 5 g/m2 ifosfamide with mesna (group B)."( Dose intensity of carboplatin in combination with cyclophosphamide or ifosfamide.
Green, JA; Smith, K, 1990)		0.28
"Cytotoxicity of cisplatin and carboplatin was compared using each drug alone and in combination with either 5-fluorouracil (5-FU) or methotrexate (MTX) and with 5-FU, vincristine (VCR) and bleomycin (BLM) together in the mouse embryo fibroblast line C3H10T1/2."( Cytotoxicity of cisplatin and carboplatin used alone and in combination with the other anticancer drugs in the mouse embryo C3H10T1/2 cell line.
Amer, MH; Hannan, MA; Hussain, SS, 1988)		0.27
" With full-dose carboplatin in combination with etoposide, there was a significantly greater carboplatin dosage administered, greater reduction in platelets, and lower platelet nadir."( A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide.
Abrams, JS; Aisner, J; Belani, CP; Egorin, MJ; Eisenberger, M; Hiponia, D; Van Echo, DA, 1989)		0.28
"Mutagenicity of cisplatin and carboplatin was compared by using the drugs alone and in combination with bleomycin, 5-fluorouracil, vincristine and methotrexate in the Ames Salmonella assay employing the tester strains TA98, TA100 (excision deficient) and TA102 (excision proficient)."( Mutagenicity of cisplatin and carboplatin used alone and in combination with four other anticancer drugs.
al-Dakan, AA; Amer, MH; Hannan, MA; Hussain, SS, 1989)		0.28
" This study showed that CHIP or CBDCA in combination with cyclophosphamide was less toxic than cisplatin/cyclophosphamide therapy with regard to alopecia, degree and duration of nausea and vomiting, renal toxicity, neurotoxicity and anaemia."( Comparative toxicity of cisplatin, carboplatin (CBDCA) and iproplatin (CHIP) in combination with cyclophosphamide in patients with advanced epithelial ovarian cancer.
Anderson, H; Brown, D; Crowther, D; Lind, MJ; McGregor, J; Palmer, P; Swindell, R; Timms, MS; Wagstaff, J, 1988)		0.27
"The nephrotoxic potentials of cisplatin and carboplatin, alone and in combination with the aminoglycoside antibiotic tobramycin, were compared in male rats."( Comparative nephrotoxicity of carboplatin and cisplatin in combination with tobramycin.
Bregman, CL; Williams, PD, 1986)		0.27
"Data from various phase I/II studies of carboplatin in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) have suggested that the degree of thrombocytopenia seen is less than that expected when carboplatin is given alone."( Carboplatin in combination with paclitaxel in advanced ovarian cancer: dose determination and pharmacokinetic and pharmacodynamic interactions.
Bailey, NP; Boddy, A; Calvert, AH; Chapman, F; Gumbrell, L; Hughes, A; Humphreys, A; Robson, L; Siddiqui, N; Thomas, H, 1995)		0.29
" However, in combination with radiation therapy, this regimen is tolerable when the primary goal is palliation of dysphagia near the end of life."( Split-course accelerated radiation therapy combined with carboplatin and 5-fluorouracil for palliation of metastatic or unresectable carcinoma of the esophagus.
Turrisi, AT; Urba, SG, 1995)		0.29
" This study assesses prospectively the results of liver resection as compared to liver resection combined with pre- and post-operative locoregional chemotherapy-immunotherapy in 40 patients suffering from hepatocellular carcinoma."( Hepatocellular carcinoma: surgical resection versus surgical resection combined with pre- and post-operative locoregional immunotherapy-chemotherapy. A prospective randomized study.
Konstantinidou, AE; Lygidakis, NJ; Pothoulakis, J; Spanos, H, )		0.13
"Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 3-hour infusion was combined with carboplatin in a phase I/II study directed to patients with non-small cell lung cancer."( Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials.
Israel, V; Jeffers, S; McRae, A; Muggia, FM; Natale, R; Rogers, M; Vafai, D; Zaretsky, S, 1995)		0.29
" To determine the optimal schedule for administration of rhu IL-3 in combination with cyclophosphamide and carboplatin, an aggressive regimen for the treatment of advanced ovarian cancer, a phase I trial was initiated by the New York Gynecologic Oncology Group."( A phase I trial of cyclosphosphamide and carboplatinum combined with interleukin-3 in women with advanced-stage ovarian cancer.
Cohen, C; Demakos, E; Hochster, H; Mandeli, J; Oette, D; Runowicz, C; Sorich, J; Speyer, JL; Wadler, S; Wallach, R, 1995)		0.29
" A pharmacologically guided phase I study of carboplatin in combination with methotrexate (30 mg/m2) and vinblastine (4 mg/m2) was conducted in ten patients by increment of the area under the plasma concentration versus time curve (AUC) for ultrafilterable carboplatin using the Calvert formula."( A pharmacologically guided phase I study of carboplatin in combination with methotrexate and vinblastine in advanced urothelial cancer.
Brunner, V; Bugat, R; Canal, P; Chatelut, E; Chevreau, C; Houin, G; Martinez, M, 1995)		0.29
"The purpose of this study was to evaluate the pharmacokinetics, biological interactions, and toxicities of ifosfamide and carboplatin combined with 41."( Ifosfamide and carboplatin combined with 41.8 degrees C whole-body hyperthermia in patients with refractory sarcoma and malignant teratoma.
Bucsky, P; d'Oleire, F; Eleftheriadis, S; Feddersen, S; Geisler, J; Klouche, M; Knop, E; Mentzel, M; Schmucker, P; Wiedemann, GJ, 1994)		0.29
" The use of radiation therapy in combination with BAI is now recommended as a more effective method."( [A study on the dosage of carboplatin for bronchial arterial infusion in combination with radiation therapy].
Higashi, K; Kobayashi, Y; Nanbu, Y; Ohguchi, M; Okimura, T; Tamamura, H; Toyota, T; Yamamoto, I; Yuasa, K, 1994)		0.29
"7% tumor growth inhibition, and these conditions for hyperthermia were subsequently used as a criterion for evaluating the effects of its combination with various anticancer agents."( Studies of effects of anticancer agents in combination with/without hyperthermia on metastasized human bladder cancer cells in chick embryos using the polymerase chain reaction technique.
Endo, Y; Kunimi, K; Lee, SW; Noguchi, M; Ohkawa, M; Sasaki, T; Uchibayashi, T, 1994)		0.29
" The seven agents combined with CI-973 were mitomycin C, cyclophosphamide, doxorubicin, vinblastine, etoposide, ifosfamide, and methotrexate."( Chemotherapy with [SP-4-3-(R)]-[1,1-cyclobutanedicarboxylato(2-)](2- methyl-1,4-butanediamine-N,N')platinum (CI-973, NK121) in combination with standard agents against murine tumors in vivo.
Elliott, WL; Howard, CT; Leopold, WR; Roberts, BJ, 1994)		0.29
"The tolerance for and activity of escalating targeted doses of carboplatin combined with ifosfamide and etoposide (ICE) were assessed in children with advanced germ cell tumors or other rare solid tumors for which no standard therapy exists."( Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in treatment of newly diagnosed pediatric solid tumors.
Bowman, LC; Furman, W; Jones, DP; Marina, NM; Meyer, WH; Murry, DJ; Pratt, CB; Rodman, JH; Shema, SJ, 1994)		0.29
"05), respectively, when combined with LL-WBH."( Therapeutic efficacy of long duration-low temperature whole body hyperthermia when combined with tumor necrosis factor and carboplatin in rats.
Bull, JM; Danhauser, LL; Jenkins, GN; Kaneko, T; Makino, M; Sakaguchi, Y; Stephens, LC; Strebel, FR, 1994)		0.29
"Acute haematological toxicity induced by cis-diammine-1,1-cyclobutane dicarboxylate platinum (II) (carboplatin) and cis-diamminedichloroplatinum (II) (cisplatin) in combination with whole body hyperthermia (WBH) (2 h at 41."( Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats.
Baba, H; Bull, JM; Khokhar, AR; Makino, M; Ohno, S; Siddik, ZH; Stephens, LC; Strebel, FR, 1993)		0.29
"Eleven patients with prostate cancer were treated by intra-arterial infusion chemotherapy and radiotherapy combined with hormone therapy."( [Clinical and pathological efficacies of intra-arterial infusion chemotherapy and radiotherapy combined with hormone therapy in prostate cancer].
Akiyama, M; Hashine, K; Inoue, Y; Sumiyoshi, Y, 1993)		0.29
" In MOLT-3 cells, supra-additive (synergistic) effects were observed for carboplatin in combination with cytosine arabinoside, mitoxantrone and CPT-11."( Effects of carboplatin in combination with other anticancer agents on human leukemia cell lines.
Akutsu, M; Kano, Y; Suzuki, K; Yoshida, M, 1993)		0.29
"The tolerance of escalating targeted doses of carboplatin combined with ifosfamide (IFOS)/etoposide (VP-16) (ICE) was assessed in children with recurrent solid tumors."( Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors.
Bowman, LC; Douglass, E; Furman, W; Hudson, M; Marina, NM; Meyer, W; Rodman, J; Santana, VM; Shema, SJ; Wilimas, J, 1993)		0.29
" These results with a small number of patients suggest that amifostine given with carboplatin may reduce the duration of thrombocytopenia and hospitalisation."( Carboplatin combined with amifostine, a bone marrow protectant, in the treatment of non-small-cell lung cancer: a randomised phase II study.
Anderson, H; Betticher, DC; Meely, K; Oster, W; Ranson, M; Thatcher, N, 1995)		0.29
"We examined the optimal timing for the enhancement of antitumor effects of CDDP analogues, cis- diammine-1,1- cyclobutane dicarboxylate platinum (II); CBDCA combined with hyperthermia against the CD-1 mice bearing Ehrlich ascites tumor (EAT) cells in vivo."( Antitumor effect of carboplatin combined with hyperthermia on Ehrlich-ascites tumor in vivo.
Mizuuchi, H; Sakurai, K; Takada, K; Tsumura, M; Yoshiga, K, )		0.13
"In a phase I study to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin administered every 21 days to women with advanced ovarian cancer, paclitaxel doses were escalated as follows: level 1, 135 mg/m2; level 2, 160 mg/m2; level 3, 185 mg/m2; and level 4,210 mg/m2."( Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer.
Bauknecht, T; Bochtler, H; Diergarten, K; du Bois, A; Köchli, O; Kreienberg, R; Kühnle, H; Lück, HJ; Meerpohl, HG; Möbus, V, 1995)		0.29
"The purpose of this phase I study is to determine the maximally tolerated doses of paclitaxel and carboplatin (dosed by area under the concentration-time curve) when given at specified times in combination with 6 g/m2 ifosfamide (3 g/m2 at 8 AM on days 1 and 2) with mesna and 5 microg/kg/d filgrastim (from day 4 until the absolute neutrophil count is > 10,000/microL) every 21 days for six cycles."( Phase I trial of dose-escalated paclitaxel and carboplatin in combination with ifosfamide and filgrastim: preliminary results.
Palackdharry, CS, 1996)		0.29
"Thrombocytopenia induced by carboplatin combined with etoposide for elderly lung cancer patients was analyzed in relation to the predicted thrombocytopenia by the equations advocated by Egorin et al."( Analysis of thrombocytopenia due to carboplatin combined with etoposide in elderly patients with lung cancer.
Bando, T; Fujimura, M; Kasahara, K; Matsuda, T; Nakatsumi, Y; Shibata, K, 1996)		0.29
"We studied the effects of carboplatin in combination with etoposide in human B-cell lymphoma cell lines, BALL-2, Dauji and human T-cell leukemia cell lines, CEM, HSB and MOLT-3 cells."( [Effects of carboplatin combination with etoposide against leukemia/lymphoma cell lines].
Akutsu, M; Kano, Y; Suzuki, K; Tsunoda, S, 1996)		0.29
" The aims of the study were to assess tolerability and feasibility of increasing doses of carboplatin (level 1: 300 mg/ m2 on day 1, level 2: 350 mg/m2 on day 1, level 3: 400 mg/m2 on day 1) in combination with a fixed dose of vinorelbine (25 mg/m2 on days 1 and 8) in advanced NSCLC."( A dose-escalating study of carboplatin combined with vinorelbine in non-small-cell lung cancer.
Boni, L; Bortolotti, L; Calabrò, F; Colleoni, M; Manente, P; Nelli, P; Pancheri, F; Sgarbossa, G; Toniolo, L; Vicario, G, )		0.13
"The introduction of platinum compounds and epipodophyllotoxins in combination with vincristine as induction chemotherapy in small-cell lung cancer (SCLC) was investigated in order to: (1) compare the efficacy of cisplatin with that of carboplatin in combination with teniposide and vincristine as inducers of remission over three cycles; (2) compare the toxicity pattern of carboplatin and of cisplatin when given in combination regimens; and (3) compare a chemotherapeutic regimen consisting of three alternating combinations with that of regimens consisting of four alternating combinations."( Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up.
Bergman, B; Dombernowsky, P; Hansen, HH; Hansen, M; Hirsch, FR; Kristjansen, PE; Lassen, U; Osterlind, K; Sigsgaard, TC, 1996)		0.29
"From November 1985 to September 1991, 484 consecutive, previously untreated patients with SCLC, performance status 0-4, entered a three armed randomized trial with three cycles of cisplatin (arm I) or carboplatin (arm II) in combination with teniposide and vincristine alternating with three treatment blocks of cyclophosphamide, etoposide, lomustine and vincristine (block A), doxorubicin and vincristine (block B) and cisplatin, hexamethylmelamine and vindesine (block C) versus alternating treatment with block A, B and C (arm III)."( Superiority of cisplatin or carboplatin in combination with teniposide and vincristine in the induction chemotherapy of small-cell lung cancer. A randomized trial with 5 years follow up.
Bergman, B; Dombernowsky, P; Hansen, HH; Hansen, M; Hirsch, FR; Kristjansen, PE; Lassen, U; Osterlind, K; Sigsgaard, TC, 1996)		0.29
" In conclusion, the partial replacement of CDDP with CBDCA in combination with VP16 slightly improves the tolerance of the treatment in terms of nephro- and neurotoxicity; however, it induces a significant increase in hematologic toxicity."( Partial substitution of cisplatin with carboplatin in combination with etoposide in advanced non-small cell lung cancer (NSCLC): a multicentric randomised phase II trial.
Biondi, E; Cioffi, R; Comella, G; Comella, P; Curcio, C; De Cataldis, G; Frasci, G; Ianniello, GP; Micillo, E; Nicolella, D; Panza, N; Perchard, J, 1996)		0.29
" We report the use of high-dose carboplatin, with the dose based on glomerular filtration rate (GFR), combined with melphalan followed by autologous stem cell rescue in children with advanced stage or chemoresistant solid tumours."( Melphalan combined with a carboplatin dose based on glomerular filtration rate followed by autologous stem cell rescue for children with solid tumours.
Pinkerton, CR; Shaw, PJ; Yaniv, I, 1996)		0.29
" It was given in combination with carboplatin, which was dosed on an AUC basis."( Etoposide phosphate infusion with therapeutic drug monitoring in combination with carboplatin dosed by area under the curve: a cancer research campaign phase I/II committee study.
Abrahamsen, D; Boddy, A; Brampton, M; Calvert, AH; Lind, M; Newell, D; Porter, D; Robson, L; Thomas, H; Winograd, B, 1996)		0.29
" Combination studies demonstrated that paclitaxel could be combined with either cisplatin or carboplatin at full doses using either a 3-hour or a 24-hour infusion schedule."( The North American experience with paclitaxel combined with cisplatin or carboplatin in lung cancer.
Bunn, PA, 1996)		0.29
"The ongoing phase I study reported here sought to determine the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin when given at specific times in combination with ifosfamide, mesna, and filgrastim."( Phase I trial of dose-escalated paclitaxel and carboplatin in combination with ifosfamide and filgrastim: preliminary results.
Palackdharry, CS, 1997)		0.3
" Thus, we started a phase I dose-escalation study to determine the maximal tolerated dose of paclitaxel given as a 3-hour infusion in combination with carboplatin, both drugs administered every 21 days."( Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer: a phase I trial.
Bauknecht, T; Bochtler, H; Diergarten, K; du Bois, A; Köchli, O; Kreienberg, R; Kühnle, H; Luck, HJ; Meerpohl, HG; Möbus, V, 1997)		0.3
"The clinical pharmacology of carboplatin (C) administered with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (P) was investigated in two phase I studies undertaken in 83 previously untreated patients with either non-small cell lung cancer or ovarian cancer."( Clinical pharmacology of carboplatin administered in combination with paclitaxel.
Beijnen, JH; Giaccone, G; Helmerhorst, TJ; Huizing, MT; Koolen, MG; Postmus, PE; ten Bokkel Huinink, WW; van der Vijgh, WJ; van Warmerdam, LJ; van Zandwijk, N; Veenhof, CH, 1997)		0.3
" ifosfamide (5 g/m2), carboplatin (300 mg/m2), and etoposide given with WBH, as well as, day 2 and 3 post-WBH (100 mg/m2) for adult patients with refractory sarcoma."( Ifosfamide, carboplatin and etoposide (ICE) combined with 41.8 degrees C whole body hyperthermia in patients with refractory sarcoma.
Crahé, R; Deeken, M; Eleftheriadis, S; Gutsche, S; Katschinski, DM; Mentzel, M; Robins, HI; Storer, B; Wagner, T; Weiss, C; Wiedemann, GJ, 1996)		0.29
" A single dose of CBDCA was combined with a single dose of radiation."( Antitumor effect of carboplatin combined with radiation on tumors in mice.
Aratani, Y; Jo, A; Mizuuchi, H; Sakurai, K; Tanimoto, K; Yoshiga, K, )		0.13
"To determine the activity, toxicity, and optimal dose of paclitaxel when given by one hour infusion combined with carboplatin in advanced non-small cell lung cancer (NSCLC)."( Phase II study of a one hour paclitaxel infusion in combination with carboplatin for advanced non-small cell lung cancer.
Dahrouge, S; Dulude, H; Earle, CC; Evans, WK; Gertler, SZ; Goel, R; Goss, G; Logan, D; Stewart, DJ; Tomiak, E, 1997)		0.3
" This review summarizes results from key phase I and II studies demonstrating the antitumor activity and tolerability of docetaxel combined with platinum compounds for patients with advanced non-small-cell lung cancer."( Docetaxel in combination with platinums in patients with advanced non-small-cell lung cancer.
Belani, CP, 1997)		0.3
" Effective modulatory doses of etanidazole could not be given with acceptable toxicity using this schedule."( Dose escalation of the hypoxic cell sensitizer etanidazole combined with ifosfamide, carboplatin, etoposide, and autologous hematopoietic stem cell support.
Antman, KH; Ayash, LJ; Coleman, N; Elias, AD; Frei, E; Ibrahim, J; McCauley, M; Mills, L; Schnipper, L; Schwartz, G; Teicher, BA; Warren, D; Wheeler, C, 1998)		0.3
" Because both P-glycoprotein- and platinum-induced resistance appear to be clinically important and can be reversed in vitro with a short exposure of cyclosporin A (CSA) at 2000 and 5000 ng/ml, respectively, we undertook a trial of high-dose chemotherapy with carboplatin (1500mg/m2), mitoxantrone (75 mg/m2), and cyclophosphamide (120 mg/kg) over a 5-day period combined with escalating doses of CSA."( High-dose chemotherapy combined with escalating doses of cyclosporin A and an autologous bone marrow transplant for the treatment of drug-resistant solid tumors: a phase I clinical trial.
Bayer, R; Camarda, M; Kinch, L; Loutfi, S; Peace, D; Rad, N; Sosman, J; Stiff, PJ; Tan, S, 1995)		0.29
" This rodent study was designed to assess the sequencing of radiation therapy and chemotherapy administered with osmotic blood-brain barrier disruption (BBBD)."( Decreased delivery and acute toxicity of cranial irradiation and chemotherapy given with osmotic blood-brain barrier disruption in a rodent model: the issue of sequence.
Garcia, R; McCormick, CI; Neuwelt, EA; Pearse, HD; Remsen, LG; Sexton, G, 1995)		0.29
", hypotension (which requires catecholamine support) results in unique nephrotoxicity in combination with select chemotherapeutic agents."( Whole-body hyperthermia combined with ifosfamide and carboplatin causes hypotension and nephrotoxicity.
Brauer, LP; Kriz, W; Pagel, H; Prieshof, B; Robins, HI; Schramm, U; Weiss, C; Wiedemann, GJ, 1998)		0.3
" This drug combination is therefore used in intraocular retinoblastoma, as primary reduction chemotherapy, before local treatment."( Role of chemotherapy alone or in combination with hyperthermia in the primary treatment of intraocular retinoblastoma: preliminary results.
Asselain, B; Desjardins, L; Doz, F; Levy, C; Michon, J; Pacquement, H; Quintana, E; Schlienger, P; Validire, P; Zucker, JM, 1998)		0.3
"In this report, we describe the development and validation of a limited-sampling model for carboplatin from 77 pharmacokinetic curves, when carboplatin is used in combination with paclitaxel."( A limited-sampling model for the pharmacokinetics of carboplatin administered in combination with paclitaxel.
Beijnen, JH; Huizing, MT; Nannan Panday, VR; Schellens, JH; Ten Bokkel Huinink, WW; van Warmerdam, LJ, 1999)		0.3
" We conducted a Phase I study of CPT-11 combined with carboplatin in previously untreated solid cancers, especially advanced lung cancer."( Phase I study of irinotecan combined with carboplatin in previously untreated solid cancers.
Fukuda, M; Kawabata, S; Kinoshita, A; Kohno, S; Nakatomi, K; Noguchi, Y; Oka, M; Soda, H; Takatani, H; Terashi, K; Tsukamoto, K; Tsurutani, J, 1999)		0.3
"In our previous study, FCCC 93-024, paclitaxel by 24-h infusion combined with carboplatin yielded a response rate of 62% and median survival of 54 weeks in advanced non-small cell lung cancer (NSCLC)."( Paclitaxel by 1-h infusion in combination with carboplatin in advanced non-small cell lung carcinoma (NSCLC).
Alexander, R; Blankstein, K; Bonjo, CA; Kosierowski, R; Langer, CJ; Litwin, S; McAleer, CA; Millenson, M; Ozols, RF, 2000)		0.31
"Although whole-body hyperthermia combined with specific genotoxic chemotherapy can be shown to enhance neoplastic cell killing without a concomitant rise in bone marrow toxicity, nephrotoxicity can become treatment-limiting."( Nephrotoxicity of ifosfamide, carboplatin and etoposide (ICE) alone or combined with extracorporeal or radiant-heat-induced whole-body hyperthermia.
Filejski, W; Gerke, P; Robins, HI; Steinhoff, J; Wiedemann, GJ, 2000)		0.31
" In order to investigate the pharmacokinetics of carboplatin in combination with Cereport, we performed pharmacological studies in conjunction with early clinical trials."( Pharmacokinetics of carboplatin administered in combination with the bradykinin agonist Cereport (RMP-7) for the treatment of brain tumours.
Bleehen, N; Boddy, AV; Calvert, AH; Ford, J; Lind, MJ; Thomas, HD, 2000)		0.31
"Cereport combined with carboplatin was well-tolerated, with mild haematological toxicities consistent with the target area under the concentration time curve (AUC) of 7 mg/ml x min."( Pharmacokinetics of carboplatin administered in combination with the bradykinin agonist Cereport (RMP-7) for the treatment of brain tumours.
Bleehen, N; Boddy, AV; Calvert, AH; Ford, J; Lind, MJ; Thomas, HD, 2000)		0.31
" The patient received ifosfamide (5 g/m2, day 1), carboplatin (300 mg/m2, day 1), etoposide (150 mg/m2, days 2-3) combined with WBH at 41."( [Chemotherapy in combination with whole-body hyperthermia in advanced malignant pleural mesothelioma].
Bakhshandeh, A; Bruns, I; Eberhardt, K; Wiedemann, GJ, 2000)		0.31
"To compare the clinical efficacy of VP-16(etoposide) with VM-26(teniposide) both plus platinum drugs combined with radiotherapy in the treatment of patients with small cell lung cancer(SCLC)."( [VP-16 and VM-26 plus platinum drugs combined with radiotherapy in the treatment of small cell lung cancer].
Jin, X; Liu, Z; Luo, B; Yin, L; Zeng, P, 1998)		0.3
" The treatment of both groups was combined with radiotherapy."( [VP-16 and VM-26 plus platinum drugs combined with radiotherapy in the treatment of small cell lung cancer].
Jin, X; Liu, Z; Luo, B; Yin, L; Zeng, P, 1998)		0.3
"The results indicate that both VP-16 and VM-26 combined with platinum drugs were effective chemotherapy protocols."( [VP-16 and VM-26 plus platinum drugs combined with radiotherapy in the treatment of small cell lung cancer].
Jin, X; Liu, Z; Luo, B; Yin, L; Zeng, P, 1998)		0.3
" Our studies examine the ability of gemcitabine, both alone and in combination with other chemotherapeutic agents, to inhibit the in vitro and in vivo growth of several prostate cancer cell lines."( The study of gemcitabine in combination with other chemotherapeutic agents as an effective treatment for prostate cancer.
Brumfield, SK; Lehr, JE; Mahoney, M; Muenchen, HJ; Pienta, KJ; Pilat, MJ; Quigley, MM, )		0.13
"To evaluate the efficacy of hyperthermic-hypoosmotic solution alone and in combination with anti-tumor drugs in the growth inhibition of human gastric cancer xenografts in immuno-compromised Balb/c mice."( [The growth-inhibiting effects of hyperthermic-hypoosmotic solution alone and in combination with chemotherapeutic agents on human gastric cancer xenograft in mice].
Chen, J; He, S; Xu, H, 1997)		0.3
"Compared with the control, in mice treated with 43 degrees C alone or in combination with one of the two chemotherapeutic agents, significantly better therapeutic effects were obtained as shown by a decrease in tumor cell Brdu labeling index (BLI), proliferation index (PI) and DNA index (DI), prolongation of survival period and reduction of CEA and hEGF contents in the peritoneal effusion."( [The growth-inhibiting effects of hyperthermic-hypoosmotic solution alone and in combination with chemotherapeutic agents on human gastric cancer xenograft in mice].
Chen, J; He, S; Xu, H, 1997)		0.3
"rhuMAbVEGF can be safely combined with chemotherapy at doses associated with VEGF blockade and without apparent synergistic toxicity."( Phase Ib trial of intravenous recombinant humanized monoclonal antibody to vascular endothelial growth factor in combination with chemotherapy in patients with advanced cancer: pharmacologic and long-term safety data.
Adelman, D; Breed, J; Fyfe, G; Gaudreault, J; Gordon, MS; Holmgren, E; Margolin, K; Novotny, W; Stalter, S, 2001)		0.31
"5 AUC according to Calvert formula on day 1, combined with vinorelbine: 25 mg/m2 on days 1 and 8, administered every 4 weeks."( Low dose carboplatin (AUC 4.5) combined with vinorelbine in the treatment of advanced non-small cell lung cancer: a single institution phase II study.
Berruti, A; Bretti, S; Celano, A; Loddo, C; Manzin, E; Ritorto, G, )		0.13
"Docetaxel (Taxotere; Aventis, Antony, France) is among the most effective agents for the treatment of non-small cell lung cancer and its use in combination with cisplatin is a logical development."( Docetaxel (Taxotere) in combination with platinums in patients with non-small cell lung cancer: trial data and implications for clinical management.
Belani, C; Lynch, T, 2001)		0.31
" A phase I trial was initiated to identify the optimal sequence and maximum-tolerated dose of topotecan in combination with paclitaxel and carboplatin."( Phase I dose escalation study of topotecan combined with alternating schedules of paclitaxel and carboplatin in advanced solid tumors.
Cantrell, CL; Dunleavy, TL; Dunphy, FR; Harrison, BR; Petruska, PJ; Pincus, SM; Richart, JM; Visconti, JL, 2001)		0.31
"To find the maximum tolerated dose for ifosfamide in combination with paclitaxel and carboplatin in small-cell lung cancer patients (SCLC), who are resistant to cyclophosphamide, doxorubicin and etoposide (CDE)."( Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer.
Beijnen, JH; Groen, HJ; Kerbush, T; Sleijfer, DT; Smit, EF; van Putten, JW; van Rijswijk, R, 2001)		0.31
"Different dose schedules of ifosfamide were combined with fixed doses of paclitaxel 175 mg/m2 and carboplatin AUC 6 mg/ml min."( Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer.
Beijnen, JH; Groen, HJ; Kerbush, T; Sleijfer, DT; Smit, EF; van Putten, JW; van Rijswijk, R, 2001)		0.31
"The maximum tolerated dose of this combination for patients with resistant SCLC is ifosfamide 2000 mg/m2 in combination with paclitaxel 175 mg/m2 and carboplatin AUC 6 mg/ml min administered on the first day of a 21-day cycle."( Dose-finding and pharmacological study of ifosfamide in combination with paclitaxel and carboplatin in resistant small-cell lung cancer.
Beijnen, JH; Groen, HJ; Kerbush, T; Sleijfer, DT; Smit, EF; van Putten, JW; van Rijswijk, R, 2001)		0.31
"To determine the effect on systemic pharmacology and clinical toxicity of dose and mode of administration of paclitaxel combined with carboplatin in the treatment of ovarian cancer."( Pharmacological study of paclitaxel duration of infusion combined with GFR-based carboplatin in the treatment of ovarian cancer.
Boddy, AV; Calvert, AH; Fishwick, K; Griffin, MJ; Highley, M; Plumner, ER; Sludden, J; Thomas, HD; Wright, JG, 2001)		0.31
"This communication represents the definitive report of a randomized phase III study comparing cisplatin and carboplatin, in combination with vindesine and mitomycin C in stage IIIB and IV squamous-cell bronchogenic carcinoma."( Survival advantage for carboplatin substituting cisplatin in combination with vindesine and mitomycin C for stage IIIB and IV squamous-cell bronchogenic carcinoma: a randomized phase III study.
Babović, N; Elezar, E; Gavrilović, D; Jelić, S; Kovacević, S; Kovcin, V; Mitrović, L; Radosavljević, D; Radulović, S; Tomasević, Z, 2001)		0.31
"The purpose of this study was to analyze the drug interactions of paclitaxel (PTX) with epirubicin (EPI), carboplatin (CBDCA), gemcitabine (GEM) and vinorelbine (VIN) in human breast cancer cells and compare the cytotoxic activity of each drug combination in primary breast cancer samples."( Drug interactions and cytotoxic effects of paclitaxel in combination with carboplatin, epirubicin, gemcitabine or vinorelbine in breast cancer cell lines and tumor samples.
Beryt, M; Felber, M; Hepp, H; Kahlert, S; Konecny, G; Langer, E; Lude, S; Pegram, M; Slamon, D; Untch, M, 2001)		0.31
"From December 1994 to July 1997, we conducted a dose escalation study of irinotecan combined with carboplatin in 17 patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum tolerated dose and the dose-limiting toxicities."( Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer.
Fukuoka, M; Negoro, S; Nitta, T; Takeda, K; Takifuji, N; Terakawa, K; Yoshimura, N, 2001)		0.31
" Our data suggest that low-dose chemotherapy in combination with PEX can be successfully used against human malignant glioma in vivo."( Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo.
Bello, L; Bikfalvi, A; Black, PM; Carrabba, G; Carroll, RS; Cerutti, F; Giussani, C; Landré, J; Lucini, V; Pluderi, M; Scaglione, F; Tomei, G; Villani, R, 2001)		0.31
"This daily-times-3-day schedule of topotecan in combination with carboplatin is safe."( A phase I/II study of topotecan in combination with carboplatin in recurrent epithelial ovarian cancer.
Bolis, G; Guarnerio, P; Parazzini, F; Polverino, GP; Rosa, C; Scarfone, G; Sciatta, C, 2001)		0.31
"Treatment with (131)I-MIBG in combination with myeloablative chemotherapy and hematopoietic stem-cell rescue is feasible with acceptable toxicity."( Pilot study of iodine-131-metaiodobenzylguanidine in combination with myeloablative chemotherapy and autologous stem-cell support for the treatment of neuroblastoma.
Braun, T; Ferrara, JL; Hubers, D; Hutchinson, RJ; Levine, JE; Matthay, KK; Shapiro, B; Shulkin, BL; Sisson, JC; Spalding, S; Yanik, GA, 2002)		0.31
" As carboplatin is less nephrotoxic and increasingly replacing cisplatin in clinical practice, the aim of this study was to define the optimal sequence and dose for topotecan in combination with carboplatin."( Topotecan in combination with carboplatin: phase I trial evaluation of two treatment schedules.
Boddy, AV; Calvert, AH; Calvert, PM; Fishwick, K; Griffin, MJ; Ross, GA; Schätzlein, A; Simpson, AB; Sludden, JA; Twelves, CJ; Wheatley, A; Wilson, P, 2002)		0.31
"The overall tumor response (complete and partial) of more than 80% indicates that chemoreduction is an effective modality alone and combined with adjuvant salvage modalities."( Efficacy of induction chemotherapy in retinoblastoma, alone or combined with other adjuvant modalities.
Arya, LS; Ghose, S; Kumar, H; Mohanti, BK; Nizamuddin, SH; Sethi, A; Thavaraj, V, )		0.13
"The purpose of this study was to determine the efficacy, tolerability, and pharmacokinetics of intraperitoneal (ip) paclitaxel combined with intravenous (iv) carboplatin and cyclophosphamide."( Kinetic modeling and efficacy of intraperitoneal paclitaxel combined with intravenous cyclophosphamide and carboplatin as first-line treatment in ovarian cancer.
Aalders, JG; Beijnen, JH; Bos, AM; de Vries, EG; Hofstra, LS; Mulder, NH; Rosing, H; van der Zee, AG; Willemse, PH; Willemsen, AT, 2002)		0.31
" Radiation (total 48 Gy) and 3 courses of chemotherapy with docetaxel (60 mg/m2) in combination with carboplatin (AUC = 6,600 mg) resulted in a remarkable reduction in the size of the mass, to less than 50%, and normalized serum CEA."( [A case of large-cell lung cancer successfully treated with docetaxel in combination with carboplatin and radiotherapy].
Kato, Y; Kitagaki, H; Maruyama, R; Nishiki, M; Tumori, M; Uchida, N; Yamane, Y; Yamauti, M; Yoshida, M, 2002)		0.31
" The choice of treatment and dose was based on a series of four phase II studies that indicated the combination of docetaxel (75 to 100 mg/m(2)) and cisplatin (75 to 100 mg/m(2)) was active and feasible; carboplatin may have a more favorable therapeutic index than cisplatin, particularly with regard to nonhematologic toxicities, and had proven activity in combination with docetaxel in phase II study; and randomized studies had shown the combination of vinorelbine plus cisplatin was superior to either vinorelbine alone or cisplatin alone and was considered as a reference study regimen in the clinical setting upon initiation of this phase III study."( Docetaxel in combination with platinums (cisplatin or carboplatin) in advanced and metastatic non-small cell lung cancer.
Belani, CP, 2002)		0.31
"To determine the maximally tolerated dose (MTD) of gemcitabine administered at a fixed dose-rate of 10 mg/m(2) per min in combination with fixed dose carboplatin, to evaluate the toxicity of this regimen and to determine the pharmacokinetics of plasma gemcitabine."( Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study.
Goh, BC; Lee, HS; Lee, SC; Lehnert, M; Lim, HL; Millward, MJ; Soo, RA; Tok, LT; Wang, LZ, 2003)		0.32
"Gemcitabine administered as a 75-min infusion at a fixed dose rate of 10 mg/m(2)/min on days 1 and 8 in combination with carboplatin on day 1 every 21 days is tolerable and active in NSCLC."( Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study.
Goh, BC; Lee, HS; Lee, SC; Lehnert, M; Lim, HL; Millward, MJ; Soo, RA; Tok, LT; Wang, LZ, 2003)		0.32
" EMP in combination with paclitaxel and carboplatin can be safely administered with hepatic toxicity being transient and reversible."( Dose escalation study of intravenous estramustine phosphate in combination with Paclitaxel and Carboplatin in patients with advanced prostate cancer.
Curley, T; Fallon, M; Hartley-Asp, B; Kelly, WK; Larson, S; Pellizzoni, C; Rocchetti, M; Scher, H; Schwartz, L; Slovin, S; Tong, W; Zhu, AX, 2003)		0.32
" The aim of this phase II study is to determine the feasibility, efficacy and toxicity of docetaxel at a dose of 75 mg/m2 in combination with Carboplatin at an area under the curve (AUC) of 6, as first line treatment in patients with advanced ovarian cancer."( Phase II clinical trial of carboplatin and docetaxel in patients with metastatic ovarian cancer: active combination with low incidence of peripheral neuropathy.
Chasen, MR; Cohen, GL; Karime, M; Mahomed, R; Rapoport, BL; Vorobiof, DA, )		0.13
"Low dose chemotherapy combined with angiogenesis inhibitors has been shown to be more effective for experimental tumor treatment than chemotherapy alone."( Low dose carboplatin combined with angiostatic agents prevents metastasis in human testicular germ cell tumor xenografts.
Abraham, D; Abri, S; Aharinejad, S; Hofmann, M; Höltl, W, 2003)		0.32
"Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial."( Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.
Averbuch, SD; Fandi, A; Giaccone, G; Grous, J; Herbst, RS; Johnson, DH; Krebs, AD; Manegold, C; Miller, V; Natale, RB; Ochs, JS; Oliff, I; Reeves, JA; Rosell, R; Scagliotti, G; Schiller, JH; Wolf, MK, 2004)		0.32
" Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy."( Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.
Averbuch, SD; Fandi, A; Giaccone, G; Grous, J; Herbst, RS; Johnson, DH; Krebs, AD; Manegold, C; Miller, V; Natale, RB; Ochs, JS; Oliff, I; Reeves, JA; Rosell, R; Scagliotti, G; Schiller, JH; Wolf, MK, 2004)		0.32
" The effect of whole-body hyperthermia (WBH) combined with platinum-containing chemotherapy in the treatment of recurrent ovarian cancer was examined in this study."( Whole-body hyperthermia in combination with platinum-containing drugs in patients with recurrent ovarian cancer.
BogoviC, J; Douwes, F; Douwes, O; Grote, C; Migeod, F, 2004)		0.32
" The effect of whole-body hyperthermia (WBH) combined with platinum-containing chemotherapy in the treatment of recurrent ovarian cancer was examined in this study."( Whole-body hyperthermia in combination with platinum-containing drugs in patients with recurrent ovarian cancer.
BogoviC, J; Douwes, F; Douwes, O; Grote, C; Migeod, F, 2004)		0.32
"To observe the effect of concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer."( [Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer].
Qiao, TK; Shu, L; Wu, W; Xin, L; Zhou, DA, 2004)		0.32
"Concurrent radiotherapy combined with carboplatin and etoposide can significantly improve median survival time and 5-year survival rate of patients with limited stage small cell lung cancer."( [Concurrent radiotherapy combined with carboplatin and etoposide in limited stage small cell lung cancer].
Qiao, TK; Shu, L; Wu, W; Xin, L; Zhou, DA, 2004)		0.32
"To determine the pharmacokinetics of adaptively dosed carboplatin when administered in combination with the bradykinin agonist, lobradimil (RMP-7, Cereport), to pediatric patients with brain tumors."( Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors.
Aikin, A; Balis, FM; Egorin, M; Gervais, A; Warren, K, 2004)		0.32
" The present study was designed to determine the toxicity and pharmacokinetics of carboplatin in combination with TNP-470 in comparison with the doublet regimen of paclitaxel and carboplatin in patients with solid tumors."( Clinical and pharmacokinetic study of TNP-470, an angiogenesis inhibitor, in combination with paclitaxel and carboplatin in patients with solid tumors.
Blumenschein, GR; Fossella, FV; Herbst, RS; Lu, C; Madden, T; Meyers, CA; Munden, R; Papadimitrakopoulou, V; Puduvalli, VK; Smythe, LG; Tran, HT; Truong, M; Zinner, R, 2004)		0.32
"Bortezomib improves efficacy in combination with gemcitabine and carboplatin in NSCLC, but sequential effects are important and must be considered when developing therapeutic regimens."( Effects of the proteasome inhibitor bortezomib alone and in combination with chemotherapy in the A549 non-small-cell lung cancer cell line.
Bold, RJ; Mortenson, MM; Schlieman, MG; Virudachalam, S, 2004)		0.32
"The aim of the study was to determine the maximum-tolerated dose and dose-limiting toxicities for BMS-184476, in combination with carboplatin, in patients with advanced solid tumours and to describe any preliminary antitumour activity associated with this regimen."( Phase I trial of the novel taxane BMS-184476 administered in combination with carboplatin every 21 days.
Bilenker, JH; Cohen, MB; Gallagher, ML; O'Dwyer, PJ; Stevenson, JP; Vaughn, D, 2004)		0.32
"5 g m(-2), carboplatin 100 mg m(-2) and etoposide 150 mg m(-2), days 1-4, q 28 days, G-CSF 5 microg kg(-1) starting from day 6) alone and in combination with regional hyperthermia (RHT) in soft tissue sarcoma (STS) refractory to previous standard doxorubicin-ifosfamide-based chemotherapy."( Ifosfamide, carboplatin and etoposide (ICE) as second-line regimen alone and in combination with regional hyperthermia is active in chemo-pre-treated advanced soft tissue sarcoma of adults.
Abdel-Rahman, S; Fahn, W; Fiegl, M; Issels, RD; Schlemmer, M; Wendtner, CM, 2004)		0.32
" A median of four courses of ICE were administered with RHT on days 1 and 3 (60 min, T(max) 42 degrees C)."( Ifosfamide, carboplatin and etoposide (ICE) as second-line regimen alone and in combination with regional hyperthermia is active in chemo-pre-treated advanced soft tissue sarcoma of adults.
Abdel-Rahman, S; Fahn, W; Fiegl, M; Issels, RD; Schlemmer, M; Wendtner, CM, 2004)		0.32
"These results suggest that ICE alone or combined with RHT shows activity as second-line therapy in doxorubicin-ifosfamide-refractory STS."( Ifosfamide, carboplatin and etoposide (ICE) as second-line regimen alone and in combination with regional hyperthermia is active in chemo-pre-treated advanced soft tissue sarcoma of adults.
Abdel-Rahman, S; Fahn, W; Fiegl, M; Issels, RD; Schlemmer, M; Wendtner, CM, 2004)		0.32
"To determine maximum tolerated dose of CI-994, a novel oral histone deacetylase inhibitor, in combination with carboplatin and paclitaxel in patients with advanced solid tumors."( Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors.
Cunningham, C; Grove, W; Kraker, A; Nemunaitis, J; Olivares, J; Olson, S; Pauer, LR; Williams, A, 2004)		0.32
" Dose escalation of paclitaxel was performed to achieve tolerability of CI-994 with a paclitaxel dose of 225 mg/m2 when administered in combination with carboplatin."( Phase I study of oral CI-994 in combination with carboplatin and paclitaxel in the treatment of patients with advanced solid tumors.
Cunningham, C; Grove, W; Kraker, A; Nemunaitis, J; Olivares, J; Olson, S; Pauer, LR; Williams, A, 2004)		0.32
" The authors used combination of lower doses of both cisplatin and carboplatin combined with etoposide (VP-16) to minimize side effects of these agents."( Double-platinum chemotherapy combined with etoposide in metastatic brain tumor from small cell lung carcinoma.
Nakayama, H; Takahashi, H; Teramoto, A; Yamada, S; Yamada, SM, 2005)		0.33
") topotecan combined with standard doses of intravenous (i."( A phase I study of intraperitoneal topotecan in combination with intravenous carboplatin and paclitaxel in advanced ovarian cancer.
Beijnen, JH; Bos, AM; De Vos, FY; de Vries, EG; Gietema, JA; Mourits, MJ; Rosing, H; van der Zee, AG; Willemse, PH, 2005)		0.33
"This phase I study was conducted to determine the toxicities, pharmacokinetics, and pharmacodynamics of BMS-214662, a farnesyl transferase inhibitor, in combination with paclitaxel and carboplatin, in patients with advanced solid tumors."( A phase I trial of the novel farnesyl protein transferase inhibitor, BMS-214662, in combination with paclitaxel and carboplatin in patients with advanced cancer.
Adjei, AA; Bruzek, LM; Cheng, S; Croghan, GA; Dy, GK; Erlichman, C; Furth, A; Hanson, LJ; Kaufmann, SH; Mandrekar, S; Martell, RE; Peethambaram, P; Pitot, HC; Reid, JM, 2005)		0.33
"Cetuximab in combination with carboplatin demonstrates clinical activity and an acceptable safety profile in heavily pretreated patients with recurrent or metastatic NPC who had previously experienced treatment failure with platinum-based therapy."( Multicenter, phase II study of cetuximab in combination with carboplatin in patients with recurrent or metastatic nasopharyngeal carcinoma.
Amellal, N; Chan, AT; Chang, AY; Goh, BC; Hong, RL; Hsu, MM; Hui, EP; Lin, X; Liu, TW; Ma, BB; Millward, MJ; Mueser, M; To, KF; Whang-Peng, J, 2005)		0.33
"The purpose of this study was to define the maximal tolerated dose (MTD), extramedullary toxicities, and pharmacokinetics of docetaxel combined with high-dose melphalan and carboplatin with autologous hematopoietic progenitor cell support."( Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies.
Barón, AE; Bearman, SI; Cagnoni, PJ; Gustafson, D; Jones, RB; Long, M; Matthes, S; McSweeney, PA; Nieto, Y; Shpall, EJ, 2005)		0.33
" A phase I study was initiated to determine whether conventional doses of carboplatin and paclitaxel are tolerated when combined with marimastat and to assess the influence of marimastat on paclitaxel pharmacokinetics."( Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Anderson, IC; Eder, JP; Goffin, JR; Johnson, BE; Lynch, TJ; Shapiro, GI; Shipp, M; Skarin, AT; Supko, JG, 2005)		0.33
" Study of this drug combination in the adjuvant setting should be considered if tissue inhibition of matrix metalloproteinase activity can first be shown."( Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Anderson, IC; Eder, JP; Goffin, JR; Johnson, BE; Lynch, TJ; Shapiro, GI; Shipp, M; Skarin, AT; Supko, JG, 2005)		0.33
" The toxicity data of 42 patients with mullerian carcinoma who underwent IP carboplatin therapy in combination with IV paclitaxel were retrospectively analyzed."( Preliminary toxicity analysis of intraperitoneal carboplatin in combination with intravenous paclitaxel chemotherapy for patients with carcinoma of the ovary, peritoneum, or fallopian tube.
Aotani, E; Fujiwara, K; Ishikawa, H; Kohno, I; Oda, T; Suzuki, S, )		0.13
"4610 in combination with carboplatin and paclitaxel in patients with advanced solid tumors."( Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGFR-1 ribozyme, in combination with carboplatin and paclitaxel in patients with advanced solid tumors.
Aitchison, RD; Basche, ML; Cooper, W; Eckhardt, SG; Holden, SN; Kobayashi, H; Lockridge, JA; O'Bryant, CL; Rothenberg, ML; Sandler, AB; Usman, N; Wolin, M, 2005)		0.33
" The ratio of the mean maximum plasma concentration (Cmax) for carboplatin when administered with paclitaxel alone versus when administered with paclitaxel and RPI."( Safety and pharmacokinetic study of RPI.4610 (ANGIOZYME), an anti-VEGFR-1 ribozyme, in combination with carboplatin and paclitaxel in patients with advanced solid tumors.
Aitchison, RD; Basche, ML; Cooper, W; Eckhardt, SG; Holden, SN; Kobayashi, H; Lockridge, JA; O'Bryant, CL; Rothenberg, ML; Sandler, AB; Usman, N; Wolin, M, 2005)		0.33
"0) in combination with exisulind (125-250 mg orally twice daily)."( A phase I/II study of exisulind in combination with docetaxel/carboplatin in patients with metastatic non-small-cell lung cancer.
Burris, HA; Dickson, NR; Greco, FA; Hainsworth, JD; Jones, SF; Kuhn, JG; Raefsky, EL; Thompson, DS; White, MB; Willcutt, NT, 2005)		0.33
"To evaluate the efficacy and safety of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN)."( Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and n
Amellal, N; Baselga, J; Bourhis, J; Cortés-Funes, H; Eckardt, A; Gascón, P; Harstrick, A; Hitt, R; Tortochaux, J; Trigo, JM, 2005)		0.33
" Erlotinib was combined with chemotherapy to determine if it could improve the outcome of patients with NSCLC."( TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer.
Fehrenbacher, L; Herbst, RS; Hermann, R; Johnson, BE; Johnson, DH; Klein, P; Kris, MG; Li, X; Miller, VA; Prager, D; Ramies, D; Sandler, A; Tran, HT, 2005)		0.33
"TRIBUTE randomly assigned patients with good performance status and previously untreated advanced (stage IIIB/IV) NSCLC to erlotinib 150 mg/d or placebo combined with up to six cycles of carboplatin and paclitaxel, followed by maintenance monotherapy with erlotinib."( TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer.
Fehrenbacher, L; Herbst, RS; Hermann, R; Johnson, BE; Johnson, DH; Klein, P; Kris, MG; Li, X; Miller, VA; Prager, D; Ramies, D; Sandler, A; Tran, HT, 2005)		0.33
"Flavopiridol, a cyclin-dependent kinase inhibitor, transcription inhibitor, and DNA-interacting agent, was combined with cisplatin or carboplatin to establish toxicities, evaluate pharmacokinetics, and examine its effects on patient cancers and levels of selected polypeptides in patient peripheral blood mononuclear cells (PBMC)."( Phase 1 trial of flavopiridol combined with cisplatin or carboplatin in patients with advanced malignancies with the assessment of pharmacokinetic and pharmacodynamic end points.
Adjei, AA; Ames, MM; Atherton, PJ; Bible, KC; Daiss, MK; Erlichman, C; Isham, CR; Kaufmann, SH; Lee, YK; Lensing, JL; Nelson, SA; Piens, J; Reid, JM; Rubin, J; Rubin, SL; Sloan, JA, 2005)		0.33
" Flavopiridol combined with carboplatin resulted in unexpectedly high toxicities and one treatment-related death."( Phase 1 trial of flavopiridol combined with cisplatin or carboplatin in patients with advanced malignancies with the assessment of pharmacokinetic and pharmacodynamic end points.
Adjei, AA; Ames, MM; Atherton, PJ; Bible, KC; Daiss, MK; Erlichman, C; Isham, CR; Kaufmann, SH; Lee, YK; Lensing, JL; Nelson, SA; Piens, J; Reid, JM; Rubin, J; Rubin, SL; Sloan, JA, 2005)		0.33
" This phase I study of oral BAY was conducted to evaluate the safety and pharmacokinetics of BAY when administered in combination with etoposide (VP-16) or in combination with VP-16 and carboplatin (CBDCA) in subjects with advanced cancer."( A phase I and pharmacokinetic study of the selective, non-peptidic inhibitor of matrix metalloproteinase BAY 12-9566 in combination with etoposide and carboplatin.
Alberts, SR; Erlichman, C; Furth, A; Lathia, CD; Molina, JR; Reid, JM; Safgren, SL; Sloan, JA, 2005)		0.33
" The purpose of this Phase I trial was to determine the maximally tolerated systemic exposure (MTSE) of topotecan in combination with carboplatin and etoposide."( A phase I trial defining the maximum tolerated systemic exposure of topotecan in combination with Carboplatin and Etoposide in extensive stage small cell lung cancer.
Donahue, A; Faucette, S; Gillenwater, HH; Kirstein, MN; Lindley, C; McCune, JS; Moore, D; Shord, S; Socinski, MA; Stewart, CF; Zamboni, WC, 2005)		0.33
"Thirty-four chemotherapy-naïve ES-SCLC patients received topotecan in combination with carboplatin AUC 5 mg/mL*min and oral etoposide 100 mg/m2/day."( A phase I trial defining the maximum tolerated systemic exposure of topotecan in combination with Carboplatin and Etoposide in extensive stage small cell lung cancer.
Donahue, A; Faucette, S; Gillenwater, HH; Kirstein, MN; Lindley, C; McCune, JS; Moore, D; Shord, S; Socinski, MA; Stewart, CF; Zamboni, WC, 2005)		0.33
"rhAngiostatin in combination with paclitaxel and carboplatin is feasible and results in a high disease control rate in patients with advanced NSCLC."( Recombinant human angiostatin (rhAngiostatin) in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer: a phase II study from Indiana University.
Dobrolecki, L; Estes, D; Hanna, N; Hickey, R; Kurup, A; Lin, C-; Mariano, L; Murry, DJ; Sidor, C; Yiannoutsos, CT, 2006)		0.33
" The aim of this study was to develop a population pharmacokinetic model describing the complex pharmacokinetics of CP, 4OHCP, 2DCECP, and PM when CP is administered in a high-dose combination with thiotepa and carboplatin."( Population pharmacokinetics of cyclophosphamide and its metabolites 4-hydroxycyclophosphamide, 2-dechloroethylcyclophosphamide, and phosphoramide mustard in a high-dose combination with Thiotepa and Carboplatin.
Beijnen, JH; de Jonge, ME; Huitema, AD; Rodenhuis, S; van Dam, SM, 2005)		0.33
"In our phase II trial, CB in combination with R showed a moderate activity with safe administration on an outpatient basis."( Carboplatin in combination with raltitrexed in recurrent and metastatic head and neck squamous cell carcinoma: A multicentre phase II study of the Gruppo Oncologico Dell'Italia Meridionale (G.O.I.M.).
Borsellino, N; Colucci, G; Di Bisceglie, M; Galetta, D; Gebbia, V; Giotta, F; Manzione, L; Rosati, G, )		0.13
"We did a phase I study, in which a fixed dose of carboplatin was combined with a dose escalation schedule of BMS-188797, both administered once every 3 weeks, in patients with advanced solid malignancies."( Phase I study of the taxane BMS-188797 in combination with carboplatin administered every 3 weeks in patients with solid malignancies.
Cantor, A; Chiappori, AA; Cohen, MB; Dellaportas, AM; Dinwoodie, WR; Fishman, MN; Garrett, CR; Gollerki, A; Lush, RM; Mahany, JJ; Simon, GR; Sullivan, DM, 2006)		0.33
"We conducted this phase II study to explore the efficacy and safety of weekly paclitaxel combined with carboplatin in elderly patients with advanced non-small cell lung cancer (NSCLC)."( A phase II study of weekly paclitaxel combined with carboplatin for elderly patients with advanced non-small cell lung cancer.
Gomi, K; Inoue, A; Ishimoto, O; Kanbe, M; Koinumaru, S; Matsubara, N; Nukiwa, T; Saijo, Y; Tanaka, M; Usui, K, 2006)		0.33
"A human ovarian cancer cell line, which migrates to mouse ovaries and establishes peritoneal carcinomatosis, was used to evaluate the cooperative effect of an antiangiogenic gene therapy combined with chemotherapy."( Adeno-associated virus-mediated delivery of a mutant endostatin in combination with carboplatin treatment inhibits orthotopic growth of ovarian cancer and improves long-term survival.
Blazar, BR; Bui Nguyen, TM; Ramakrishnan, S; Subramanian, IV; Tolar, J; Truskinovsky, AM, 2006)		0.33
" Individual, selective sensitivities were found for each drug combination tested."( Ex vivo chemosensitivity of head and neck carcinoma to cytostatic drug combinations.
Dietz, A; Dollner, R; Granzow, C; Neudert, M, )		0.13
"To determine the efficacy and toxicity of irinotecan combined with carboplatin, we conducted a phase II trial."( Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer.
Fukuda, M; Kinoshita, A; Kohno, S; Kuba, M; Nagashima, S; Nakamura, Y; Oka, M; Soda, H; Takatani, H; Tsurutani, J, 2006)		0.33
"Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m2) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m2/d."( Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
Amellal, N; Awada, A; Borel, C; Bourhis, J; Duck, L; Geoffrois, L; Harstrick, A; Hitt, R; Humblet, Y; Lopez-Pousa, A; Mesia, R; Rivera, F; Rosine, D; Schueler, A; Vega Villegas, ME, 2006)		0.33
" An FU dose of 1,000 mg/m2/d in combination with cisplatin or carboplatin can be recommended for additional studies."( Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.
Amellal, N; Awada, A; Borel, C; Bourhis, J; Duck, L; Geoffrois, L; Harstrick, A; Hitt, R; Humblet, Y; Lopez-Pousa, A; Mesia, R; Rivera, F; Rosine, D; Schueler, A; Vega Villegas, ME, 2006)		0.33
"To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response."( Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.
Boellaard, R; Crezee, H; Hoekstra, OS; Hulshof, MC; Omloo, JM; Sloof, GW; ten Kate, FJ; van Lanschot, JJ; Vervenne, WL; Westerterp, M, 2006)		0.33
"FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia."( Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.
Boellaard, R; Crezee, H; Hoekstra, OS; Hulshof, MC; Omloo, JM; Sloof, GW; ten Kate, FJ; van Lanschot, JJ; Vervenne, WL; Westerterp, M, 2006)		0.33
" Two different treatment schedules of bortezomib in combination with paclitaxel and carboplatin were tested in this phase I study to evaluate the effects of scheduling on toxicities, pharmacodynamics and clinical activity."( A phase I and pharmacologic study of sequences of the proteasome inhibitor, bortezomib (PS-341, Velcade), in combination with paclitaxel and carboplatin in patients with advanced malignancies.
Adjei, AA; Alberts, SR; Bruzek, L; Croghan, GA; Erlichman, C; Hanson, LJ; Jatoi, A; Ma, C; Mandrekar, SJ; Pitot, HC; Reid, JM; Tan, AD; Wright, JJ, 2007)		0.34
" The tumours were treated with different doses of platinum compounds, alone or combined with the local application of electric pulses to the tumour (electrochemotherapy)."( Cytotoxicity of different platinum (II) analogues to human tumour cell lines in vitro and murine tumour in vivo alone or combined with electroporation.
Bukovec, N; Cemazar, M; Grabner, S; Pipan, Z; Sersa, G, )		0.13
" Intratumoral injection of 3P-SK alone or combined with electroporation (electrochemotherapy) induced significant tumour growth delay and tumour cure."( Cytotoxicity of different platinum (II) analogues to human tumour cell lines in vitro and murine tumour in vivo alone or combined with electroporation.
Bukovec, N; Cemazar, M; Grabner, S; Pipan, Z; Sersa, G, )		0.13
" In the experimental tumour model of mammary carcinoma, treatment with 3P-SK, alone or in combination with electroporation, was less effective compared to CDDP, but nevertheless resulted in tumour growth inhibition after a single application."( Cytotoxicity of different platinum (II) analogues to human tumour cell lines in vitro and murine tumour in vivo alone or combined with electroporation.
Bukovec, N; Cemazar, M; Grabner, S; Pipan, Z; Sersa, G, )		0.13
" Because of its wide spectrum of actions, it is reasonable to consider the combination with other anticancer drugs in clinical application."( Cytotoxic effects of histone deacetylase inhibitor FK228 (depsipeptide, formally named FR901228) in combination with conventional anti-leukemia/lymphoma agents against human leukemia/lymphoma cell lines.
Akutsu, M; Furukawa, Y; Izumi, T; Kano, Y; Kobayashi, H; Mano, H; Tsunoda, S, 2007)		0.34
"We have previously shown that interferon-gamma 1b (IFN-gamma) in combination with cyclophosphamide and cisplatin significantly prolongs progression-free survival in ovarian cancer."( Interferon-gamma in combination with carboplatin and paclitaxel as a safe and effective first-line treatment option for advanced ovarian cancer: results of a phase I/II study.
Estermann, K; Hausmaninger, H; Marth, C; Mueller-Holzner, E; Pelzer, A; Petru, E; Windbichler, GH, )		0.13
" All patients received antimitotic agents combined with platinum chemotherapy."( Eg5 expression is closely correlated with the response of advanced non-small cell lung cancer to antimitotic agents combined with platinum chemotherapy.
Goto, K; Ishii, G; Kato, H; Nagai, K; Nishiwaki, Y; Ochiai, A; Saijo, N; Saijo, T; Yoh, K, 2006)		0.33
"Eg5 expression can predict a response to antimitotic agents combined with platinum chemotherapy among patients with advanced NSCLC."( Eg5 expression is closely correlated with the response of advanced non-small cell lung cancer to antimitotic agents combined with platinum chemotherapy.
Goto, K; Ishii, G; Kato, H; Nagai, K; Nishiwaki, Y; Ochiai, A; Saijo, N; Saijo, T; Yoh, K, 2006)		0.33
"To investigate the immunoregulation and short-term therapeutic effects of super-selective intra-arterial chemotherapy combined with Fuzheng Kang'ai Granules, a compound Chinese herbal medicine, on patients with late gastric cancer."( [Immunoregulation and short-term therapeutic effects of super-selective intra-arterial chemotherapy combined with traditional Chinese drugs on gastric cancer patients].
Fang, C; Song, MQ; Sun, Q; Wang, L; Zhu, JS; Zhu, L, 2006)		0.33
"The super-selective intra-arterial chemotherapy combined with Fuzheng Kang'ai Granules has good short-term therapeutic efficiency and few side effects for patients with late gastric antrum cancer."( [Immunoregulation and short-term therapeutic effects of super-selective intra-arterial chemotherapy combined with traditional Chinese drugs on gastric cancer patients].
Fang, C; Song, MQ; Sun, Q; Wang, L; Zhu, JS; Zhu, L, 2006)		0.33
"To evaluate the toxicity profile and pharmacological properties of oral CP-547,632 alone and in combination with paclitaxel and carboplatin administered every 3 weeks, and to assess efficacy as measured by the objective response and progressive disease rates of oral CP-547,632 administered in combination with paclitaxel and carboplatin."( A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC).
Cohen, RB; Cosgriff, TM; Eisenberg, PD; Hainsworth, JD; Healey, D; Langer, CJ; Liau, K; Madajewicz, S; Pierce, K; Simon, GR; Xu, H, 2007)		0.34
"Patients with stage IIIB/IV or recurrent non-small cell lung cancer receiving first-line chemotherapy were treated with oral daily CP-547,632 in combination with paclitaxel 225 mg/m(2) and carboplatin AUC = 6 every 3 weeks."( A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC).
Cohen, RB; Cosgriff, TM; Eisenberg, PD; Hainsworth, JD; Healey, D; Langer, CJ; Liau, K; Madajewicz, S; Pierce, K; Simon, GR; Xu, H, 2007)		0.34
" Dose-limiting toxicity of CP-547,632 250 mg by mouth daily in combination with paclitaxel and carboplatin was grade 3 rash and grade 3 diarrhea despite medical intervention."( A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC).
Cohen, RB; Cosgriff, TM; Eisenberg, PD; Hainsworth, JD; Healey, D; Langer, CJ; Liau, K; Madajewicz, S; Pierce, K; Simon, GR; Xu, H, 2007)		0.34
"To assess the feasibility of administering erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, in combination with paclitaxel and carboplatin, and to identify pharmacokinetic interactions, evaluate downstream effects of EGFR inhibition on surrogate tissues, and seek preliminary evidence for clinical activity."( Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors.
Beeram, M; Hamilton, M; Hammond, LA; Hidalgo, M; Kreisberg, JI; Mita, MM; Nadler, P; Patnaik, A; Rowinsky, EK; Schwartz, G; Tolcher, AW; Wolf, J; Wood, D, 2006)		0.33
"A dose level of erlotinib 125 mg combined with paclitaxel 225 mg/m(2) and carboplatin AUC 6 mg."( Phase I, pharmacokinetic, and biological study of erlotinib in combination with paclitaxel and carboplatin in patients with advanced solid tumors.
Beeram, M; Hamilton, M; Hammond, LA; Hidalgo, M; Kreisberg, JI; Mita, MM; Nadler, P; Patnaik, A; Rowinsky, EK; Schwartz, G; Tolcher, AW; Wolf, J; Wood, D, 2006)		0.33
"To investigate the effects of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid (NM-3) alone and in combination with carboplatin on tumor growth and apoptosis in mouse models of human gastric cancer constructed by subcutaneous implantation of histologically intact tumor tissue."( Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo.
Chen, JL; Chen, MX; Chen, NW; Chen, WX; Hong, J; Lu, JL; Shen, B; Zhu, JS; Zhu, ZM, 2007)		0.34
" NM-3 was injected peritoneally at the dose of 10 mg/kg, 20 mg/kg or 40 mg/kg every other day for 5 wk, combined with carboplatin (5 mg/kg) every third day for 4 wk."( Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo.
Chen, JL; Chen, MX; Chen, NW; Chen, WX; Hong, J; Lu, JL; Shen, B; Zhu, JS; Zhu, ZM, 2007)		0.34
" But NM-3 in combination with carboplatin had greater effects of tumor weight than either NM-3 or carboplatin alone."( Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo.
Chen, JL; Chen, MX; Chen, NW; Chen, WX; Hong, J; Lu, JL; Shen, B; Zhu, JS; Zhu, ZM, 2007)		0.34
" Furthermore, NM-3 alone at the dose of 10 mg/kg or in combination with carboplatin has no obvious effects on body changes, indicating that NM-3 in combination with carboplatin may be effective in the treatment of gastric cancer."( Effect of 2-(8-hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl) propionic acid in combination with carboplatin on gastric carcinoma growth in vivo.
Chen, JL; Chen, MX; Chen, NW; Chen, WX; Hong, J; Lu, JL; Shen, B; Zhu, JS; Zhu, ZM, 2007)		0.34
" A significant reduction in glutathione synthetase and glutathione reductase transcripts by indisulam provided a molecular basis for its combination with platinum agents."( A phase I and pharmacokinetic study of indisulam in combination with carboplatin.
Dittrich, C; Gneist, M; Huitema, AD; King, AA; Wanders, J; Zandvliet, AS, 2007)		0.34
"The objective of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors."( Phase I study of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors: preliminary evidence of activity in small cell and neuroendocrine carcinomas.
Antonia, S; Chiappori, A; de Lima Lopes, G; Haura, E; Langevin, M; Lush, R; Rocha-Lima, CM; Simon, G; Sullivan, D, 2007)		0.34
"Carboplatin in combination with gemcitabine and irinotecan was feasible."( Phase I study of carboplatin in combination with gemcitabine and irinotecan in patients with solid tumors: preliminary evidence of activity in small cell and neuroendocrine carcinomas.
Antonia, S; Chiappori, A; de Lima Lopes, G; Haura, E; Langevin, M; Lush, R; Rocha-Lima, CM; Simon, G; Sullivan, D, 2007)		0.34
"Administration of paclitaxel on a weekly schedule in combination with carboplatin is associated with a lower incidence of neuropathy and myelosuppression."( Treatment of elderly non-small cell lung cancer patients with three different schedules of weekly paclitaxel in combination with carboplatin: subanalysis of a randomized trial.
Barstis, J; Belani, CP; Clark, R; La Rocca, RV; Mills, GM; Nattam, SR; Perry, MC; Ramalingam, S; Rinaldi, D, 2006)		0.33
"The weekly regimen of paclitaxel administered in combination with carboplatin is tolerated well by elderly NSCLC patients and has comparable efficacy with younger patients."( Treatment of elderly non-small cell lung cancer patients with three different schedules of weekly paclitaxel in combination with carboplatin: subanalysis of a randomized trial.
Barstis, J; Belani, CP; Clark, R; La Rocca, RV; Mills, GM; Nattam, SR; Perry, MC; Ramalingam, S; Rinaldi, D, 2006)		0.33
"We designed this phase II trial to evaluate the efficacy and safety of weekly paclitaxel in combination with monthly carboplatin as first-line treatment in elderly patients with advanced non-small cell lung cancer (NSCLC)."( Weekly paclitaxel combined with monthly carboplatin in elderly patients with advanced non-small cell lung cancer: a multicenter phase II study.
Breton, JL; Debieuvre, D; Depierre, A; Gervais, R; Hominal, S; Milleron, B; Molinier, O; Namouni, F; Pujol, JL; Quoix, E; Tonelli, D, 2006)		0.33
"Paclitaxel-carboplatin, combined with CI-1033 at 100 mg/day, was safe and well tolerated."( A phase I evaluation of oral CI-1033 in combination with paclitaxel and carboplatin as first-line chemotherapy in patients with advanced non-small cell lung cancer.
Bitran, JD; Burnett, D; Chiappori, AA; Eiseman, I; Ellis, PM; Hamm, JT; Lenehan, P; Lovalvo, J; Olson, S; Zinner, RG, 2006)		0.33
"We wanted to determine whether transcatheter Ethiodol-based capillary embolization in combination with carboplatin could improve the efficiency of a 1:1 Ethiodol-ethanol mixture (EEM) to ablate kidneys that been inoculated with VX-2 carcinoma."( Transcatheter arterial embolization of renal VX-2 carcinoma: ethiodol-ethanol capillary embolization combined with carboplatin.
Choi, BG; Kónya, A; Van Pelt, CS; Wright, KC, )		0.13
"None of the Ethiodol-based modalities combined with locoregional carboplatin were more efficacious for tumor ablation than EEM alone."( Transcatheter arterial embolization of renal VX-2 carcinoma: ethiodol-ethanol capillary embolization combined with carboplatin.
Choi, BG; Kónya, A; Van Pelt, CS; Wright, KC, )		0.13
"The primary objective of this study was to determine the recommended phase II doses of the novel histone deacetylase inhibitor vorinostat when administered in combination with carboplatin and paclitaxel."( Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies.
Argiris, AE; Belani, CP; Egorin, MJ; Lagattuta, TF; Musguire, LA; Parise, RA; Potter, DM; Ramalingam, SS; Ramananthan, RK; Ramanathan, RK; Stoller, RG; Zwiebel, JA, 2007)		0.34
"Both schedules of vorinostat (400 mg oral qd x 14 days or 300 mg bd x 7 days) were tolerated well in combination with carboplatin (area under the concentration versus time curve = 6 mg/mL x min) and paclitaxel (200 mg/m(2))."( Phase I and pharmacokinetic study of vorinostat, a histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies.
Argiris, AE; Belani, CP; Egorin, MJ; Lagattuta, TF; Musguire, LA; Parise, RA; Potter, DM; Ramalingam, SS; Ramananthan, RK; Ramanathan, RK; Stoller, RG; Zwiebel, JA, 2007)		0.34
" The present phase Ib study examined the safety/tolerability and pharmacokinetics of patupilone in combination with carboplatin in patients with advanced solid tumors."( A phase Ib and pharmacokinetic trial of patupilone combined with carboplatin in patients with advanced cancer.
Cheung, W; Forster, M; Gore, M; Johri, A; Kaye, S; Oza, A; Sklenar, I; Zaknoen, S, 2007)		0.34
") administration of carboplatin by means of convection-enhanced delivery (CED) in combination with fractionated, external beam photon irradiation for the treatment of F98 glioma-bearing rats."( Enhanced survival and cure of F98 glioma-bearing rats following intracerebral delivery of carboplatin in combination with photon irradiation.
Balosso, J; Barth, RF; Boudou, C; Elleaume, H; Estève, F; Rousseau, J, 2007)		0.34
" administration of carboplatin by means of CED in combination with either 6-MV or 80-keV photons."( Enhanced survival and cure of F98 glioma-bearing rats following intracerebral delivery of carboplatin in combination with photon irradiation.
Balosso, J; Barth, RF; Boudou, C; Elleaume, H; Estève, F; Rousseau, J, 2007)		0.34
"This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the proteasome inhibitor bortezomib when combined with carboplatin in ovarian cancer patients with recurrent and platinum- and taxane-resistant disease."( Phase I trial of the proteasome inhibitor bortezomib in combination with carboplatin in patients with platinum- and taxane-resistant ovarian cancer.
Coleman, RL; Gershenson, DM; Johnston, TA; Landen, CN; Levenback, C; Milam, MR; Ramirez, PT, 2008)		0.35
" This study aimed to evaluate molecular and cellular effects of rapamycin in a panel of cell lines either as single agent or in combination with cytotoxics commonly used in HNSCC."( Antiproliferative effects of rapamycin as a single agent and in combination with carboplatin and paclitaxel in head and neck cancer cell lines.
Aissat, N; Bieche, I; Faivre, S; Ghoul, A; Le Tourneau, C; Lokiec, F; Raymond, E; Serova, M, 2008)		0.35
" Additive and synergistic effects were observed when rapamycin was combined with carboplatin and paclitaxel."( Antiproliferative effects of rapamycin as a single agent and in combination with carboplatin and paclitaxel in head and neck cancer cell lines.
Aissat, N; Bieche, I; Faivre, S; Ghoul, A; Le Tourneau, C; Lokiec, F; Raymond, E; Serova, M, 2008)		0.35
"The purpose of this trial was to define the maximum tolerated duration (MTD), dose-limiting toxicity (DLT), regimen-related toxicities (RRT), and pharmacokinetics of gemcitabine infused at a fixed dose rate (FDR) of 10 mg/m2/min, combined with docetaxel/melphalan/carboplatin, using autologous stem cell transplantation (ASCT)."( Phase I and pharmacokinetic study of gemcitabine administered at fixed-dose rate, combined with docetaxel/melphalan/carboplatin, with autologous hematopoietic progenitor-cell support, in patients with advanced refractory tumors.
Aldaz, A; Aramendía, JM; Aristu, J; Centeno, C; Hernández, M; Moreno, M; Nieto, Y; Pérez-Calvo, J; Rifón, J; Sayar, O; Viteri, S; Viúdez, A; Zafra, A; Zufia, L, 2007)		0.34
" The schedule was pemetrexed 500 mg/m(2) in combination with carboplatin area under the curve 5, every 21 days."( Phase II study of pemetrexed in combination with carboplatin in patients with malignant pleural mesothelioma (MPM).
Aitini, E; Alabiso, O; Botta, M; Buosi, R; Carbone, R; Castagneto, B; Degiovanni, D; Galbusera, V; Giaretto, L; Mencoboni, M; Muzio, A; Piccolini, E; Rebella, L; Serra, M; Spigno, F, 2008)		0.35
" Bevacizumab (B) in combination with carboplatin (C) and paclitaxel (P) improves survival for advanced, nonsquamous NSCLC, as evidenced in Eastern Cooperative Oncology Group (ECOG) 4599."( Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599.
Belani, CP; Brahmer, JR; Dahlberg, SE; Gray, R; Johnson, DH; Langer, CJ; Ramalingam, SS; Sandler, AB; Schiller, JH, 2008)		0.35
" We conducted a phase I study of gemcitabine and carboplatin in combination with bortezomib."( The proteasome inhibitor bortezomib in combination with gemcitabine and carboplatin in advanced non-small cell lung cancer: a California Cancer Consortium Phase I study.
Bold, R; Davies, AM; Gandara, DR; Gumerlock, PH; Lara, PN; Lau, DH; Lenz, HJ; Ruel, C; Schenkein, DP; Shibata, S, 2008)		0.35
"To compare the efficacy and safety of weekly paclitaxel in combination with carboplatin administered every 4 weeks to the standard regimen of paclitaxel and carboplatin administered every 3 weeks for the treatment of patients with advanced non-small-cell lung cancer (NSCLC)."( Randomized, phase III study of weekly paclitaxel in combination with carboplatin versus standard every-3-weeks administration of carboplatin and paclitaxel for patients with previously untreated advanced non-small-cell lung cancer.
Belani, CP; Gable, PS; LaRocca, RV; Perry, MC; Ramalingam, S; Rinaldi, D; Tester, WJ, 2008)		0.35
" This study was designed to assess the influence of atrasentan on paclitaxel pharmacokinetics and to determine the safety and efficacy of atrasentan in combination with paclitaxel-carboplatin."( Phase I/II study of atrasentan, an endothelin A receptor antagonist, in combination with paclitaxel and carboplatin as first-line therapy in advanced non-small cell lung cancer.
Antonia, S; Bepler, G; Boulware, D; Burton, M; Chiappori, AA; Haura, E; Kapoor, R; Lush, R; Neuger, AM; Padilla, B; Rodriguez, FA; Simon, G; Sullivan, DM; Williams, C, 2008)		0.35
" This study was designed with the primary objective to estimate the patients' preference for po or iv vinorelbine in combination with carboplatin for the palliative treatment of non-small cell lung cancer (NSCLC)."( Randomized cross-over study of patient preference for oral or intravenous vinorelbine in combination with carboplatin in the treatment of advanced NSCLC.
Jensen, LH; Osterlind, K; Rytter, C, 2008)		0.35
" After Lewis cells (1 x 10(7)) inoculation, the mice received irradiated GM-CSF secreting cancer vaccine solely or in combination with carboplatin."( [The anti-tumor activity of GM-CSF-modified lung cancer cell vaccine and its synergism in combination with chemotherapy].
Jiang, HJ; Li, H; Ma, MQ; Ren, XB; Wei, F; Yu, JP, 2007)		0.34
" This study evaluated escalating doses of AZD2171 in combination with standard chemotherapy in patients with advanced non-small-cell lung cancer."( Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institut
Arnold, A; Chen, E; Ellis, PM; Gauthier, I; Goss, G; Laurie, SA; Powers, J; Puchalski, TA; Robertson, J; Seymour, L; Shepherd, FA; Tu, D; Walsh, W, 2008)		0.35
"AZD2171 can be combined with standard doses of carboplatin/paclitaxel with encouraging antitumor activity."( Phase I and pharmacokinetic study of daily oral AZD2171, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer: the National Cancer Institut
Arnold, A; Chen, E; Ellis, PM; Gauthier, I; Goss, G; Laurie, SA; Powers, J; Puchalski, TA; Robertson, J; Seymour, L; Shepherd, FA; Tu, D; Walsh, W, 2008)		0.35
"This phase I trial assessed the safety and tolerability of G3139 when given in combination with carboplatin and paclitaxel chemotherapy."( A phase I pharmacokinetic and pharmacodynamic correlative study of the antisense Bcl-2 oligonucleotide g3139, in combination with carboplatin and paclitaxel, in patients with advanced solid tumors.
Alberti, D; Eickhoff, J; Kolesar, J; Lee, F; Leith, C; Liu, G; Marnocha, R; McNeel, DG; Schell, K; Traynor, A; Wilding, G; Zwiebel, J, 2008)		0.35
" Proliferation assays were performed with single agent Imatinib or combined with Paclitaxel and Carboplatin."( Novel treatment of ovarian cancer cell lines with Imatinib mesylate combined with Paclitaxel and Carboplatin leads to receptor-mediated antiproliferative effects.
Bauerschlag, DO; Hilpert, F; Jonat, W; Maass, N; Meinhold-Heerlein, I; Mundhenke, C; Roesel, F; Schem, C; Sturner, KH; Weigel, MT, 2008)		0.35
"To compare the safety and efficacy of carboplatin and paclitaxel administered with or without the multidrug resistance modulator valspodar (PSC 833) in untreated patients with advanced ovarian or primary peritoneal cancer."( Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer.
Baekelandt, MM; Dugan, MH; Fracasso, PM; Gordon, AN; Joly, F; Jones, GJ; Lhommé, C; Lissoni, AA; Manikhas, GM; Mietlowski, WL; Nicoletto, MO; Walker, JL, 2008)		0.35
"The aim of this study was to evaluate the safety and tolerability of escalating doses of flavopiridol/ paclitaxel/carboplatin in patients with advanced-stage non-small-cell lung cancer (NSCLC) as well as the pharmacokinetics and activity of flavopiridol when used in combination with paclitaxel/carboplatin."( Phase I study of flavopiridol in combination with Paclitaxel and Carboplatin in patients with non-small-cell lung cancer.
Bukowski, RM; Cogswell, J; Fidias, P; George, S; Kasimis, BS; Schwarzenberger, P; Shapiro, GI, 2008)		0.35
"This study evaluated the safety, maximum tolerated dose, pharmacokinetics, and antitumor activity of sorafenib, a multikinase inhibitor, combined with paclitaxel and carboplatin in patients with solid tumors."( A phase I trial of the oral, multikinase inhibitor sorafenib in combination with carboplatin and paclitaxel.
Albertini, MR; Brose, MS; Elder, D; Flaherty, KT; Hingorani, SR; Jacobetz, MA; Lathia, C; Liu, G; O'Dwyer, PJ; Petrenciuc, O; Redlinger, M; Schiller, J; Schuchter, LM; Tuveson, DA; Van Belle, PA; Weber, BL; Xia, C, 2008)		0.35
"To determine the maximum tolerated dose (MTD), spectrum of toxicities, clinical activity, and pharmacokinetics of carboplatin given in combination with lapatinib in women with a first recurrence of platinum sensitive epithelial ovarian carcinoma."( A phase I study of lapatinib in combination with carboplatin in women with platinum sensitive recurrent ovarian carcinoma.
Alvarez, RD; Barnes, MN; Estes, JM; Kimball, KJ; Kirby, TO; Koch, KM; Matei, DE; Numnum, TM; Zamboni, WC, 2008)		0.35
" Cohorts of 3-6 patients were to receive up to 6 cycles of intravenous carboplatin AUC of 6 every 21 days in combination with escalating dosages of oral lapatinib (starting at a dose of 750 mg daily)."( A phase I study of lapatinib in combination with carboplatin in women with platinum sensitive recurrent ovarian carcinoma.
Alvarez, RD; Barnes, MN; Estes, JM; Kimball, KJ; Kirby, TO; Koch, KM; Matei, DE; Numnum, TM; Zamboni, WC, 2008)		0.35
" The anti-tumor activities of risedronate in combination with carboplatin, doxorubicin, vincristine or etoposide were assayed with CalcuSyn (Biosoft)."( Efficacy of the third-generation bisphosphonate risedronate alone and in combination with anticancer drugs against osteosarcoma cell lines.
Kawasoe, Y; Komiya, S; Minami, S; Murayama, T; Ueno, Y; Yamashita, Y; Yokouchi, M, )		0.13
" When administered in combination with carboplatin and docetaxel, a commonly used regimen for advanced NSCLC, cetuximab has exhibited synergistic interaction in preclinical studies."( Cetuximab in combination with carboplatin and docetaxel for patients with metastatic or advanced-stage nonsmall cell lung cancer: a multicenter phase 2 study.
Belani, CP; Butler, EH; Guidice, RA; Marsland, TA; Ramalingam, SS; Schreeder, MT; Steis, RG, 2008)		0.35
" Based on promising results of a pilot study, we initiated a phase II study with WBH and carboplatin in pretreated patients with advanced ovarian cancer to investigate the toxicity and efficacy of WBH in combination with carboplatin."( Whole-body hyperthermia (WBH) in combination with carboplatin in patients with recurrent ovarian cancer - a phase II study.
Al-Batran, SE; Atmaca, A; Jäger, D; Jäger, E; Knuth, A; Kolassa, Y; Neumann, A, 2009)		0.35
"This study confirms that WBH in combination with carboplatin is an active salvage treatment option in patients with advanced ovarian cancer."( Whole-body hyperthermia (WBH) in combination with carboplatin in patients with recurrent ovarian cancer - a phase II study.
Al-Batran, SE; Atmaca, A; Jäger, D; Jäger, E; Knuth, A; Kolassa, Y; Neumann, A, 2009)		0.35
"This phase II study assessed the efficacy and safety of oral vinorelbine given weekly in combination with carboplatin (CBDCA) AUC 5 once every 3 weeks for four cycles in chemonaive patients with advanced non-small cell lung carcinoma (NSCLC), followed by consolidation therapy with single-agent oral vinorelbine in non-progressive patients."( Phase II study of oral vinorelbine in combination with carboplatin followed by consolidation therapy with oral vinorelbine as single-agent in unresectable localized or metastatic non-small cell lung carcinoma.
Abratt, R; Cornes, P; Del Barco, S; Macha, HN; Morand, M; Reck, M; Riggi, M; Vaissière, N, 2009)		0.35
"The combination of oral vinorelbine given weekly in 3-week cycles in combination with carboplatin followed by consolidation therapy with oral vinorelbine as a single-agent was able to achieve efficacy results in line with other doublets including carboplatin in terms of response as well as survival."( Phase II study of oral vinorelbine in combination with carboplatin followed by consolidation therapy with oral vinorelbine as single-agent in unresectable localized or metastatic non-small cell lung carcinoma.
Abratt, R; Cornes, P; Del Barco, S; Macha, HN; Morand, M; Reck, M; Riggi, M; Vaissière, N, 2009)		0.35
") administration of carboplatin by means of ALZET osmotic pumps, in combination with radiotherapy for the treatment of intracranial F98 glioma in rats."( Efficacy of intracerebral delivery of Carboplatin in combination with photon irradiation for treatment of F98 glioma-bearing rats.
Barth, RF; Elleaume, H; Moeschberger, ML; Rousseau, J, 2009)		0.35
" infusion of carboplatin by means of ALZET pumps in combination with X-irradiation is highly effective for the treatment of the F98 glioma."( Efficacy of intracerebral delivery of Carboplatin in combination with photon irradiation for treatment of F98 glioma-bearing rats.
Barth, RF; Elleaume, H; Moeschberger, ML; Rousseau, J, 2009)		0.35
" From January 1991, we randomly selected 26 patients with locally advanced stage IIIb cervical cancer to receive radiotherapy combined with TAI of 120 mg/body cisplatin twice a month at an interval of 4 weeks."( Distribution of platinum in the female genital tract and efficacy of radiotherapy combined with transcatheter arterial infusion of cisplatin for locally advanced stage IIIb carcinoma of the uterine cervix.
Ito, K; Kaneyasu, Y; Komatsu, M; Nagai, N; Oshita, T; Shiroyama, Y; Watasaki, S, 2009)		0.35
"To analyse the treatment results of neo-adjuvant chemoradiation combined with regional hyperthermia in patients with resectable esophageal cancer."( Preoperative chemoradiation combined with regional hyperthermia for patients with resectable esophageal cancer.
Crezee, J; Fockens, P; Geijsen, ED; Hulshof, MC; Oldenborg, S; Richel, DJ; Van Berge Henegouwen, MI; Van Haaren, PM; Van Lanschot, JJ, 2009)		0.35
"Neo-adjuvant chemoradiation combined with regional hyperthermia followed by esophageal resection for patients with esophageal cancer resulted in good locoregional control and overall survival."( Preoperative chemoradiation combined with regional hyperthermia for patients with resectable esophageal cancer.
Crezee, J; Fockens, P; Geijsen, ED; Hulshof, MC; Oldenborg, S; Richel, DJ; Van Berge Henegouwen, MI; Van Haaren, PM; Van Lanschot, JJ, 2009)		0.35
"In a single-institution phase II study, we sought to determine the effectiveness of concurrent chemoradiation given with celecoxib and examined biomarkers to predict response to COX-2 inhibition."( A phase II study of celecoxib in combination with paclitaxel, carboplatin, and radiotherapy for patients with inoperable stage IIIA/B non-small cell lung cancer.
Carbone, DP; Choy, H; Csiki, I; Johnson, DH; Lu, B; Moretti, L; Morrow, JD; Mutter, R; Sandler, AB; Shyr, Y; Ye, F, 2009)		0.35
" As such, we conditionally deleted Brca2 and p53 within murine mammary epithelium and treated the resulting tumors in situ with a highly potent PARP-1 inhibitor (AZD2281) alone or in combination with carboplatin."( Poly(ADP-ribose) polymerase-1 inhibitor treatment regresses autochthonous Brca2/p53-mutant mammary tumors in vivo and delays tumor relapse in combination with carboplatin.
Clarke, AR; Cranston, A; Douglas-Jones, A; Hay, T; Lau, A; Martin, NM; Matthews, JR; Nygren, AO; O'Connor, M; Pietzka, L; Smith, GC, 2009)		0.35
" The purpose of this study was to prepare carboplatin-Fe@C-loaded chitosan nanoparticles with Fe@C as a magnetic core and to investigate efficacy of hyperthermia combined with chemotherapy for transplanted liver cancer in rats."( Preparation of carboplatin-Fe@C-loaded chitosan nanoparticles and study on hyperthermia combined with pharmacotherapy for liver cancer.
Guo, YH; Li, FR; Qi, H; Yan, WH; Zhou, HX, 2009)		0.35
" The therapeutic effect of hyperthermia combined with chemotherapy for tumor, toxicity and rat survival time were observed."( Preparation of carboplatin-Fe@C-loaded chitosan nanoparticles and study on hyperthermia combined with pharmacotherapy for liver cancer.
Guo, YH; Li, FR; Qi, H; Yan, WH; Zhou, HX, 2009)		0.35
"The aim of this trial was to investigate the efficacy and toxicity of a relative high-dose of topotecan combined with carboplatin in recurrent or persistent epithelial ovarian cancer (EOC)."( Topotecan combined with carboplatin in recurrent epithelial ovarian cancer: results of a single-institutional phase II study.
Bae, DS; Choi, CH; Kang, H; Kim, BG; Kim, TJ; Lee, JW; Lee, YY, 2009)		0.35
"0 mg/m(2)/day intravenously (IV) on days 1 to 5 in combination with carboplatin AUC 5 IV on day 5, every 21 days."( Topotecan combined with carboplatin in recurrent epithelial ovarian cancer: results of a single-institutional phase II study.
Bae, DS; Choi, CH; Kang, H; Kim, BG; Kim, TJ; Lee, JW; Lee, YY, 2009)		0.35
"The relative high-dose of topotecan combined with carboplatin was feasible and produced modest activity in recurrent or persistent EOC."( Topotecan combined with carboplatin in recurrent epithelial ovarian cancer: results of a single-institutional phase II study.
Bae, DS; Choi, CH; Kang, H; Kim, BG; Kim, TJ; Lee, JW; Lee, YY, 2009)		0.35
"The efficacy of intravenous administration of 400 mg carboplatin/m(2) body surface area over 60 minutes combined with hyperbaric oxygenation (HBO) therapy (0."( Pharmacokinetic investigation of increased efficacy against malignant gliomas of carboplatin combined with hyperbaric oxygenation.
Hashimoto, T; Negishi, D; Shimizu, M; Suzuki, Y; Tanaka, K; Yamazaki, H; Yoshida, Y, 2009)		0.35
"This primary objective of this phase I dose-escalation study was to define the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of larotaxel administered in combination with carboplatin in chemotherapy-naïve patients with advanced/metastatic non-small cell lung cancer (NSCLC)."( A phase I study of larotaxel (XRP9881) administered in combination with carboplatin in chemotherapy-naïve patients with stage IIIB or stage IV non-small cell lung cancer.
Ackerman, J; Gupta, S; Harper, K; Robert, F, 2010)		0.36
"To investigate the cytotoxicity of TRA-8, an antibody that specifically binds death receptor 5, alone and in combination with chemotherapy, using an ex vivo human ovarian cancer model."( Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy in an ex vivo human ovarian cancer model.
Alvarez, RD; Buchsbaum, DJ; Della Manna, DL; Frederick, PJ; Grizzle, WE; Kendrick, JE; Lin, HY; LoBuglio, AF; Oliver, PG; Stockard, CR; Straughn, JM; Zhou, T, 2009)		0.35
" The additive and synergistic cytotoxic effects of chemotherapy combination with TRA-8 were evaluated in specimens."( Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy in an ex vivo human ovarian cancer model.
Alvarez, RD; Buchsbaum, DJ; Della Manna, DL; Frederick, PJ; Grizzle, WE; Kendrick, JE; Lin, HY; LoBuglio, AF; Oliver, PG; Stockard, CR; Straughn, JM; Zhou, T, 2009)		0.35
"This study demonstrates the efficacy of the death receptor monoclonal antibody TRA-8 in combination with conventional chemotherapy in an ex vivo human ovarian cancer model."( Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy in an ex vivo human ovarian cancer model.
Alvarez, RD; Buchsbaum, DJ; Della Manna, DL; Frederick, PJ; Grizzle, WE; Kendrick, JE; Lin, HY; LoBuglio, AF; Oliver, PG; Stockard, CR; Straughn, JM; Zhou, T, 2009)		0.35
" We hypothesized that targeted inhibition of specific signaling pathways in combination with conventional drugs may increase chemotherapeutic efficacy."( Rapamycin by itself and additively in combination with carboplatin inhibits the growth of ovarian cancer cells.
Chan, JL; Li, W; Lin, KT; Schlosshauer, PW; Wang, LH, 2009)		0.35
" The effect of several PI3K pathway inhibitors (rapamycin, LY294002, SH-6) and rapamycin in combination with carboplatin on various tumor cell growth characteristics was tested in cell lines and fresh tumor-derived transient monolayer and organ cultures."( Rapamycin by itself and additively in combination with carboplatin inhibits the growth of ovarian cancer cells.
Chan, JL; Li, W; Lin, KT; Schlosshauer, PW; Wang, LH, 2009)		0.35
"Rapamycin in combination with standard chemotherapeutic agents may improve the efficiency of ovarian cancer treatment."( Rapamycin by itself and additively in combination with carboplatin inhibits the growth of ovarian cancer cells.
Chan, JL; Li, W; Lin, KT; Schlosshauer, PW; Wang, LH, 2009)		0.35
"To evaluate the efficacy of Endosteal(TM) (rh-endostatin, YH-16) combined with docetaxel and carboplatin (TP) regimen for the adjuvant treatment of non-small lung cancer (NSCLC) and its impact on circulating blood markers."( [rh-endostatin in combination with docetaxel and carboplatin as adjuvant treatment for non-small lung cancer].
Cui, Y; Feng, K; Liu, ZJ; Qi, DL; Qiao, YF; Wang, QS; Xin, L; Yang, YZ, 2009)		0.35
"Endosteal(TM) combined with TP regimen seem to be superior to TP alone in some short term index for the treatment of postoperative NSCLC even though long-term survival is still anticipated."( [rh-endostatin in combination with docetaxel and carboplatin as adjuvant treatment for non-small lung cancer].
Cui, Y; Feng, K; Liu, ZJ; Qi, DL; Qiao, YF; Wang, QS; Xin, L; Yang, YZ, 2009)		0.35
"We designed a phase I clinical trial of escalating doses of topotecan with CY and carboplatin in combination with autologous hematopoietic SCT (AHSCT) for the treatment of relapsed or persistent platinum sensitive ovarian or primary peritoneal carcinoma."( Phase I trial of autologous hematopoietic SCT with escalating doses of topotecan combined with CY and carboplatin in patients with relapsed or persistent ovarian or primary peritoneal carcinoma.
Ames, MM; Ansell, SM; Barrette, BA; Dispenzieri, A; Elliott, MA; Frost, MH; Gastineau, DA; Gertz, MA; Hartmann, LC; Inwards, DJ; Kaufmann, SH; Keeney, GL; Lacy, MQ; Lingle, WL; Litzow, MR; Long, HJ; Micallef, IN; Peethambaram, PP; Porrata, LF; Reid, JM; Safgren, SL; Suman, VJ, 2010)		0.36
"A phase I study assessed the safety, tolerability, pharmacokinetics, and preliminary antitumor effect of mapatumumab, a fully-human agonist monoclonal antibody to the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1, DR4), in combination with paclitaxel and carboplatin."( Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study.
Camidge, DR; Chow, LQ; Cohen, RB; Diab, S; Eckhardt, SG; Fox, NL; Gore, L; Gustafson, DL; Hariharan, S; Langer, CJ; Leong, S; Miceli, R; O'Bryant, C; Padavic, K; Smith, M; von Mehren, M, 2009)		0.35
"Mapatumumab is well-tolerated up to 20 mg/kg in combination with paclitaxel and carboplatin."( Mapatumumab, an antibody targeting TRAIL-R1, in combination with paclitaxel and carboplatin in patients with advanced solid malignancies: results of a phase I and pharmacokinetic study.
Camidge, DR; Chow, LQ; Cohen, RB; Diab, S; Eckhardt, SG; Fox, NL; Gore, L; Gustafson, DL; Hariharan, S; Langer, CJ; Leong, S; Miceli, R; O'Bryant, C; Padavic, K; Smith, M; von Mehren, M, 2009)		0.35
"We aimed to evaluate the safety and efficacy of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy in patients with locally advanced or metastatic non-small cell lung cancer."( Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer.
Belt, RJ; Boccia, RV; Brown, GL; Burris, HA; Caldwell, DC; Edelman, MJ; Englund, CW; Fidias, PM; Huberman, MS; Jones, M; Keck, JG; Kolevska, T; Lynch, TJ; Melnyk, O; Meng, L; Mills, GM; Rabin, MS; Sequist, LV; Temel, JS, 2009)		0.35
"A phase I trial was performed to evaluate the administration of carboplatin/paclitaxel in combination with ISIS-5132, a phosphorothioate antisense oligodeoxynucleotide inhibitor of c-raf-1 kinase expression, in patients with advanced non-small cell lung cancer (NSCLC)."( Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer.
Boral, AL; Eder, JP; Fidias, P; Geary, RS; Johnson, BE; Kwoh, TJ; Lynch, TJ; Pennell, NA; Shapiro, GI; Skarin, AT; Supko, JG, 2009)		0.35
"ISIS 5132 can be safely combined with standard doses of carboplatin and paclitaxel."( Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer.
Boral, AL; Eder, JP; Fidias, P; Geary, RS; Johnson, BE; Kwoh, TJ; Lynch, TJ; Pennell, NA; Shapiro, GI; Skarin, AT; Supko, JG, 2009)		0.35
"This phase 1 study was conducted to determine the recommended phase 2 dose of the selective insulin-like growth factor type 1 receptor (IGF-IR) inhibitor figitumumab (F, CP-751,871) given in combination with paclitaxel and carboplatin in patients with advanced solid tumors."( Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel and carboplatin.
Cardenal, F; Cohen, RB; Demers, L; Eisenberg, PD; Garland, L; Gualberto, A; Haluska, P; Hixon, ML; Karp, DD; Langer, CJ; Leitzel, K; Lipton, A; Paz-Ares, LG; Pollak, MN; Terstappen, LW; Yin, D, 2009)		0.35
"F was well tolerated in combination with paclitaxel and carboplatin."( Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel and carboplatin.
Cardenal, F; Cohen, RB; Demers, L; Eisenberg, PD; Garland, L; Gualberto, A; Haluska, P; Hixon, ML; Karp, DD; Langer, CJ; Leitzel, K; Lipton, A; Paz-Ares, LG; Pollak, MN; Terstappen, LW; Yin, D, 2009)		0.35
" This phase I trial was conducted to evaluate drug safety and pharmacokinetics as well as tumor response of sorafenib in combination with paclitaxel and carboplatin in patients with advanced non-small cell lung cancer (NSCLC)."( Phase I clinical and pharmacokinetic study of sorafenib in combination with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Fukino, K; Fukuoka, M; Hasegawa, Y; Kaneda, H; Kawada, A; Miyazaki, M; Morinaga, R; Nakagawa, K; Okamoto, I; Satoh, T; Tanigawa, T; Ueda, S, 2010)		0.36
"The present study confirmed that sorafenib at 400 mg once daily in combination with carboplatin AUC 5 mg min mL(-1) and paclitaxel 200 mg/m(2) is feasible in Japanese patients with advanced NSCLC."( Phase I clinical and pharmacokinetic study of sorafenib in combination with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Fukino, K; Fukuoka, M; Hasegawa, Y; Kaneda, H; Kawada, A; Miyazaki, M; Morinaga, R; Nakagawa, K; Okamoto, I; Satoh, T; Tanigawa, T; Ueda, S, 2010)		0.36
" We hypothesized that thalidomide, an oral antiangiogenic agent, when combined with chemotherapy, and as maintenance treatment, would improve survival in patients with advanced non-small-cell lung cancer (NSCLC)."( Randomized double-blind placebo-controlled trial of thalidomide in combination with gemcitabine and Carboplatin in advanced non-small-cell lung cancer.
Gilligan, D; Gower, N; Hackshaw, A; Jitlal, M; Lee, SM; Ottensmeier, C; Price, A; Rudd, R; Spiro, S; Woll, PJ, 2009)		0.35
"In this large trial of patients with NSCLC, thalidomide in combination with chemotherapy did not improve survival overall, but increased the risk of thrombotic events."( Randomized double-blind placebo-controlled trial of thalidomide in combination with gemcitabine and Carboplatin in advanced non-small-cell lung cancer.
Gilligan, D; Gower, N; Hackshaw, A; Jitlal, M; Lee, SM; Ottensmeier, C; Price, A; Rudd, R; Spiro, S; Woll, PJ, 2009)		0.35
" We conducted a randomized phase II study to compare the efficacy and safety of weekly paclitaxel combined with carboplatin with those of the standard schedule."( Randomized phase II trial of weekly paclitaxel combined with carboplatin versus standard paclitaxel combined with carboplatin for elderly patients with advanced non-small-cell lung cancer.
Abe, T; Inoue, A; Ishida, T; Kanbe, M; Maemondo, M; Nukiwa, T; Saijo, Y; Sakakibara, T; Sugawara, S; Usui, K; Watanabe, H, 2010)		0.36
"Amrubicin combined with carboplatin is quite effective for SCLC with acceptable toxic effects even for the elderly population."( A phase II study of amrubicin combined with carboplatin for elderly patients with small-cell lung cancer: North Japan Lung Cancer Study Group Trial 0405.
Fukuhara, T; Fukumoto, S; Harada, M; Harada, T; Inoue, A; Ishimoto, O; Kanbe, M; Maemondo, M; Nukiwa, T; Ogura, S; Oizumi, S; Sugawara, S; Suzuki, T; Usui, K; Yokouchi, H, 2010)		0.36
"This phase I, open-label study investigated the Toll-like receptor 9 agonist, PF-3512676, in combination with carboplatin and paclitaxel in Japanese patients with advanced, non-small-cell lung cancer (NSCLC)."( Phase I study of TLR9 agonist PF-3512676 in combination with carboplatin and paclitaxel in patients with advanced non-small-cell lung cancer.
Fukuyama, C; Hashimoto, J; Kunitoh, H; Nakao, M; Nokihara, H; Ohe, Y; Ohki, E; Sekine, I; Tamura, T; Yamada, K; Yamamoto, N, 2010)		0.36
"The purpose of the phase I dose-escalation study was to evaluate the maximum tolerated dose (MTD) of BIBF 1120, an oral triple angiokinase inhibitor of vascular endothelial growth factor, platelet derived growth factor and fibroblast growth factor receptors, combined with paclitaxel and carboplatin."( A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies.
du Bois, A; Harter, P; Huober, J; Loibl, S; Pfisterer, J; Reichardt, VL; Stopfer, P; Wimberger, P, 2010)		0.36
") continuously at 100, 150, 200 or 250 mg, combined with paclitaxel (175 mg/m(2)) and carboplatin (area under the curve 5 min."( A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies.
du Bois, A; Harter, P; Huober, J; Loibl, S; Pfisterer, J; Reichardt, VL; Stopfer, P; Wimberger, P, 2010)		0.36
" This combination had an acceptable safety profile and no clinically relevant drug-drug interactions."( A phase I open-label dose-escalation study of oral BIBF 1120 combined with standard paclitaxel and carboplatin in patients with advanced gynecological malignancies.
du Bois, A; Harter, P; Huober, J; Loibl, S; Pfisterer, J; Reichardt, VL; Stopfer, P; Wimberger, P, 2010)		0.36
" This phase II randomized, double-blinded, placebo-controlled study evaluated the efficacy of vorinostat in combination with carboplatin and paclitaxel in patients with advanced-stage NSCLC."( Carboplatin and Paclitaxel in combination with either vorinostat or placebo for first-line therapy of advanced non-small-cell lung cancer.
Argiris, AE; Belani, CP; Espinoza-Delgado, I; Frankel, P; Gandara, DR; Gitlitz, B; Koczywas, M; Maitland, ML; Ramalingam, SS; Thomas, S; Vokes, EE, 2010)		0.36
"This phase II study is performed to evaluate the safety, efficacy and tolerability of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer (NSCLC)."( Phase II study of carboplatin combined with weekly docetaxel in patients with advanced non-small cell lung cancer.
Hou, XH; Jiang, L; Tang, LF; Wang, DF; Wang, DY; Xie, Z; Zhao, HD; Zhu, ZH, 2010)		0.36
"Treatment with motesanib was tolerable when combined with carboplatin/paclitaxel and/or panitumumab, with little effect on motesanib pharmacokinetics at the 125-mg once daily dose level."( Phase 1b study of motesanib, an oral angiogenesis inhibitor, in combination with carboplatin/paclitaxel and/or panitumumab for the treatment of advanced non-small cell lung cancer.
Blumenschein, GR; Gladish, G; McGreivy, J; O'Rourke, T; Parson, M; Reckamp, K; Sandler, A; Stephenson, GJ; Sun, YN; Ye, Y, 2010)		0.36
" Twenty-three patients experiencing progression following 6 months after concluding platinum-based chemotherapy were managed with second-line treatment with carboplatin combined with gemcitabine or pemetrexed."( High response of second-line chemotherapy with pemetrexed or gemcitabine combined with carboplatin in patients with non-small-cell lung cancer experiencing progression following 6 months after concluding platinum-based chemotherapy.
Arrieta, O; Astorga, A; Flores-Estrada, D; Martinez-Barrera, L; Michel Ortega, RM; Pachuca, D; Villarreal-Garza, C, 2011)		0.37
"PURPOSE Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF) with demonstrated efficacy in combination with carboplatin and paclitaxel (PCB) for the treatment of advanced non-small-cell lung cancer (NSCLC)."( Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599.
Brahmer, JR; Dahlberg, SE; Johnson, DH; Sandler, AB; Schiller, JH, 2010)		0.36
"To assess the pharmacokinetics and evaluate potential drug-drug interactions between erlotinib, paclitaxel and carboplatin."( Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC).
Blumenschein, GR; Herbst, RS; Kim, ES; Lu, C; Lum, BL; Malik, M; Oh, YW; Papadimitrakopoulou, VA; Tran, HT; Zinner, RG, 2011)		0.37
"1,079 previously untreated patients with advanced NSCLC were enrolled and randomized in a phase III trial (TRIBUTE) to receive either erlotinib or placebo in combination with paclitaxel 200 mg/m2 IV over 3 h and carboplatin at a calculated dose to achieve an AUC 6 mg∙min/mL."( Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial (TRIBUTE) of paclitaxel and carboplatin combined with erlotinib or placebo in patients with advanced Non-small Cell Lung Cancer (NSCLC).
Blumenschein, GR; Herbst, RS; Kim, ES; Lu, C; Lum, BL; Malik, M; Oh, YW; Papadimitrakopoulou, VA; Tran, HT; Zinner, RG, 2011)		0.37
"This phase II investigated efficacy and tolerability of gefitinib in combination with paclitaxel (P) and carboplatin (C) for second-line treatment of patients (pts) with ovarian, tubal or peritoneal adenocarcinoma."( Phase II study of gefitinib in combination with paclitaxel (P) and carboplatin (C) as second-line therapy for ovarian, tubal or peritoneal adenocarcinoma (1839IL/0074).
Bougnoux, P; Carrasco, AT; Fumoleau, P; Joly, F; Kerbrat, P; Lhommé, C; Pautier, P; Petit, T; Ringeisen, F; Rixe, O, 2010)		0.36
"Gefitinib, administered in combination with paclitaxel and carboplatin, provides a good clinical response but associated with an increased risk of hematologic disorders."( Phase II study of gefitinib in combination with paclitaxel (P) and carboplatin (C) as second-line therapy for ovarian, tubal or peritoneal adenocarcinoma (1839IL/0074).
Bougnoux, P; Carrasco, AT; Fumoleau, P; Joly, F; Kerbrat, P; Lhommé, C; Pautier, P; Petit, T; Ringeisen, F; Rixe, O, 2010)		0.36
"To determine the safety, pharmacokinetics (PK), and maximum-tolerated dose (MTD) up to a prespecified target dose of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab (PCB) in patients with previously untreated, nonsquamous, stage IIIb (with pleural effusion)/IV or recurrent non-small-cell lung cancer (NSCLC)."( Phase 1b study of dulanermin (recombinant human Apo2L/TRAIL) in combination with paclitaxel, carboplatin, and bevacizumab in patients with advanced non-squamous non-small-cell lung cancer.
Besse, B; Blackhall, F; Hsu, CP; Khayat, D; Reese, D; Smit, E; Soria, JC; Wiezorek, J; Yang, X, 2010)		0.36
" An MTD was not reached, and the drug combination was well tolerated."( Phase 1b study of dulanermin (recombinant human Apo2L/TRAIL) in combination with paclitaxel, carboplatin, and bevacizumab in patients with advanced non-squamous non-small-cell lung cancer.
Besse, B; Blackhall, F; Hsu, CP; Khayat, D; Reese, D; Smit, E; Soria, JC; Wiezorek, J; Yang, X, 2010)		0.36
" Dulanermin at 8 mg/kg/d for 5 days and 20 mg/kg/d for 2 days every 3 weeks in combination with PCB is being studied in a phase II trial."( Phase 1b study of dulanermin (recombinant human Apo2L/TRAIL) in combination with paclitaxel, carboplatin, and bevacizumab in patients with advanced non-squamous non-small-cell lung cancer.
Besse, B; Blackhall, F; Hsu, CP; Khayat, D; Reese, D; Smit, E; Soria, JC; Wiezorek, J; Yang, X, 2010)		0.36
" vinorelbine 25 mg/m(2) on day 1 and oral vinorelbine 60 mg/m(2) on day 8 given with carboplatin area under the curve (AUC) 5 once every 3 weeks (q3w) for four cycles followed by consolidation therapy with single-agent vinorelbine in non-progressive patients with advanced non-small-cell lung cancer (NSCLC)."( Vinorelbine in combination with carboplatin followed by single-agent consolidation therapy for unresectable localized or metastatic non-small-cell lung carcinomas.
Alici, S; Alkis, N; Altunbas, M; Benekli, M; Buyukberber, S; Celenkoglu, G; Coskun, U; Dane, F; Gumus, M; Kaya, AO; Ozkan, M; Sevinc, A, 2009)		0.35
" Paclitaxel was delivered at 80-100mg/m2 on days 1 and 8 (11 cases), or 50-80 mg/m2 on days 1, 8 and 15 (23 cases), while docetaxel was given with the same schedules at 35-45 mg/m2 (30cases), or 25-35 mg/m2 (14 cases)."( Weekly paclitaxel/ docetaxel combined with a platinum in the treatment of advanced non-small cell lung cancer: a study on efficacy, safety and pre-medication.
Huang, XE; Jiang, W; Li, C; Lin, Y; Shi, MQ; Shu, YQ; Sunh, WL; Ye, Z; Zhang, Q; Zhou, JN, 2009)		0.35
"We evaluated the feasibility and toxicity of bevacizumab in combination with sequential high-dose (HD) ifosfamide, carboplatin and etoposide refractory to standard chemotherapy in patients with sarcoma and germ cell cancer (GCC)."( Bevacizumab in combination with sequential high-dose chemotherapy in solid cancer, a feasibility study.
Arnold, D; Behlendorf, T; Jordan, K; Kegel, T; Mueller, LP; Schmoll, HJ; Sippel, C; Voigt, W; Wolf, HH, 2010)		0.36
" Brain metastasis was detected in one patient at 7 months after initial therapy and was treated with stereotactic radiotherapy combined with whole brain irradiation."( Carboplatin and etoposide combined with radiotherapy for limited-stage small-cell esophageal carcinoma: three cases and review of the literature.
Atsumi, K; Hirata, H; Honda, H; Isoyama, Y; Matsuura, S; Nomoto, S; Nonoshita, T; Ohga, S; Onishi, K; Shioyama, Y; Terashima, K, 2010)		0.36
"CBDCA and VP-16 in combination with radiotherapy should be considered an important treatment option for SCEC."( Carboplatin and etoposide combined with radiotherapy for limited-stage small-cell esophageal carcinoma: three cases and review of the literature.
Atsumi, K; Hirata, H; Honda, H; Isoyama, Y; Matsuura, S; Nomoto, S; Nonoshita, T; Ohga, S; Onishi, K; Shioyama, Y; Terashima, K, 2010)		0.36
" The patients were treated with either compound Kusheng injection in combination with NP (NVB + CBP) chemotherapy (vinorelbine and carboplatin, n = 144), or with NP (NVB + CBP) chemotherapy alone (n = 142)."( [Enhancing effect of compound Kusheng injection in combination with chemotherapy for patients with advanced non-small cell lung cancer].
Cui, J; Fan, CX; Liang, L; Lin, CL; Liu, J; Wang, YL; Yang, QM; Zhang, AR; Zhao, YY, 2010)		0.36
" We treated six patients with recurrent GBM using bevacizumab combined with carboplatin and etoposide chemotherapy (ACE regimen)."( Carboplatin and etoposide combined with bevacizumab for the treatment of recurrent glioblastoma multiforme.
Dupre, S; Francesconi, AB; Hughes, BG; Lickliter, JD; Martin, D; Matos, M; Wyld, DK, 2010)		0.36
" On the basis of preclinical studies indicating that hypomethylating agents can reverse platinum resistance in ovarian cancer cells, the authors conducted a phase 1 trial of low-dose decitabine combined with carboplatin in patients with recurrent, platinum-resistant ovarian cancer."( A phase 1 and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer.
Balch, C; Breen, T; Fang, F; Kulesavage, C; Li, L; Matei, DE; Nephew, KP; Schilder, J; Shen, C; Snyder, AJ; Zhang, S, 2010)		0.36
"Repetitive low-dose decitabine is tolerated when combined with carboplatin in ovarian cancer patients, and demonstrates biological (ie, DNA-hypomethylating) activity, justifying further testing for clinical efficacy."( A phase 1 and pharmacodynamic study of decitabine in combination with carboplatin in patients with recurrent, platinum-resistant, epithelial ovarian cancer.
Balch, C; Breen, T; Fang, F; Kulesavage, C; Li, L; Matei, DE; Nephew, KP; Schilder, J; Shen, C; Snyder, AJ; Zhang, S, 2010)		0.36
"The purpose of this study was to further evaluate the therapeutic efficacy of convection enhanced delivery (CED) of carboplatin in combination with radiotherapy for treatment of the F98 rat glioma."( Convection enhanced delivery of carboplatin in combination with radiotherapy for the treatment of brain tumors.
Barth, RF; Chou, TC; Elleaume, H; Grecula, JC; Gupta, N; Hoff, BA; Huo, T; Ross, BD; Rousseau, J; Weldon, M; Yang, W, 2011)		0.37
"A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle."( A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients.
Bernard, S; Chiu, M; Davies, JM; Dees, EC; Dhruva, NS; Hayes, DN; Hilbun, LR; Ivanova, A; Keller, K; Kim, WY; Socinski, MA; Stinchcombe, TE; Walko, CM, 2011)		0.37
"The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m² every 3 weeks."( A phase I trial of sorafenib combined with cisplatin/etoposide or carboplatin/pemetrexed in refractory solid tumor patients.
Bernard, S; Chiu, M; Davies, JM; Dees, EC; Dhruva, NS; Hayes, DN; Hilbun, LR; Ivanova, A; Keller, K; Kim, WY; Socinski, MA; Stinchcombe, TE; Walko, CM, 2011)		0.37
"Gefitinib (250 mg daily) in combination with RT and CDDP in patients with Stage III NSCLC is feasible, but CDDP likely enhances toxicity."( Gefitinib in combination with irradiation with or without cisplatin in patients with inoperable stage III non-small cell lung cancer: a phase I trial.
Aebersold, DM; Bernier, J; Bucher, SE; Ciernik, IF; Glanzmann, C; Lippuner, T; Lombrieser, N; Lütolf, UM; Ries, G; Rothschild, S; Zouhair, A, 2011)		0.37
"This trial aimed to define a recommended safe dose (RSD) of weekly paclitaxel and irinotecan combined with carboplatin in patients with advanced cancer."( Phase I trial of weekly irinotecan and paclitaxel combined with carboplatin in patients with advanced cancer: a Hellenic Cooperative Oncology Group Study.
Briasoulis, E; Fountzilas, G; Golfinopoulos, V; Karina, M; Papakostas, P; Pavlidis, N, 2010)		0.36
"To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of gemcitabine-carboplatin (Gem-Carbo) for the treatment of patients with platinum-sensitive recurrent ovarian cancer (PSROC) by reviewing the published literature."( Tolerability, efficacy, and safety of pegylated liposomal Doxorubicin in combination with Carboplatin versus gemcitabine-Carboplatin for the treatment of platinum-sensitive recurrent ovarian cancer: a systematic review.
Grendys, EC; Holloway, RW; Lefebvre, P; McMeekin, S; Vekeman, F, 2010)		0.36
" From June 2010, we have been conducting a randomized Phase II/III trial of intravenous versus intraperitoneal administration of carboplatin every 3 week in combination with dose-dense weekly administration of paclitaxel."( A randomized Phase II/III trial of 3 weekly intraperitoneal versus intravenous carboplatin in combination with intravenous weekly dose-dense paclitaxel for newly diagnosed ovarian, fallopian tube and primary peritoneal cancer.
Aoki, D; Aotani, E; Fujiwara, K; Hamano, T; Katsumata, N; Kigawa, J; Nagao, S; Sugiyama, T; Suzuki, M; Takeuchi, M; Yoshikawa, H, 2011)		0.37
" We conducted this study to investigate its efficacy and safety when combined with chemotherapy in patients with advanced solid tumors."( Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors.
Huang, XE; Jiang, Y; Li, Y; Xiang, J; Yan, PW, 2010)		0.36
"5 mg/m2 /day as an intravenous infusion for more than 7 days, in combination with chemotherapy."( Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors.
Huang, XE; Jiang, Y; Li, Y; Xiang, J; Yan, PW, 2010)		0.36
"Our study revealed that toxicity of Endostar combined with chemotherapy in the treatment of solid tumors was tolerable with moderate efficacy."( Efficacy and safety of endostar combined with chemotherapy in patients with advanced solid tumors.
Huang, XE; Jiang, Y; Li, Y; Xiang, J; Yan, PW, 2010)		0.36
"To evaluate the maximum tolerated dose (MTD), safety, and antitumor activity of sunitinib combined with paclitaxel and carboplatin."( Sunitinib in combination with paclitaxel plus carboplatin in patients with advanced solid tumors: phase I study results.
Blumenschein, GR; Chao, RC; Cohen, RB; Heath, EI; Kim, ST; Loconte, NK; Lorusso, PM; Ruiz-Garcia, A; Wilding, G, 2011)		0.37
"5, or 50 mg) for 2 consecutive weeks of a 3-week cycle (Schedule 2/1) or as a continuous daily dose for 3-week cycles (CDD schedule) in combination with paclitaxel (175-200 mg/m(2)) plus carboplatin (AUC 6 mg min/ml) on day one of each of 4 cycles."( Sunitinib in combination with paclitaxel plus carboplatin in patients with advanced solid tumors: phase I study results.
Blumenschein, GR; Chao, RC; Cohen, RB; Heath, EI; Kim, ST; Loconte, NK; Lorusso, PM; Ruiz-Garcia, A; Wilding, G, 2011)		0.37
" PK data indicated an increase in maximum and total plasma exposures to sunitinib and its active metabolite when given with paclitaxel and carboplatin compared with sunitinib monotherapy."( Sunitinib in combination with paclitaxel plus carboplatin in patients with advanced solid tumors: phase I study results.
Blumenschein, GR; Chao, RC; Cohen, RB; Heath, EI; Kim, ST; Loconte, NK; Lorusso, PM; Ruiz-Garcia, A; Wilding, G, 2011)		0.37
" In this study, the safety and tolerability, pharmacokinetics and pharmacodynamics of ASA404 in combination with standard therapy of paclitaxel and carboplatin (P/C) were assessed."( Phase I study of intravenous ASA404 (vadimezan) administered in combination with paclitaxel and carboplatin in Japanese patients with non-small cell lung cancer.
Hida, T; Hirashima, T; Horai, T; Horio, Y; Kobayashi, K; Nishio, M; Shi, MM; Tamiya, M; Tanii, H; Yamamoto, N, 2011)		0.37
" We evaluated the efficacy of TRA-8, an agonistic antibody to DR5, combined with docetaxel and carboplatin in vitro in an intraperitoneal (IP) ovarian cancer model."( Anti-tumor activity of an anti-DR5 monoclonal antibody, TRA-8, in combination with taxane/platinum-based chemotherapy in an ovarian cancer model.
Amm, H; Bevis, KS; Buchsbaum, DJ; Della Manna, D; Londoño Joshi, A; McNally, LR; Sellers, JC; Straughn, JM, 2011)		0.37
"Conventional chemotherapy combined with TRA-8 reduced cell-viability via activation of apoptotic pathways, reduced tumor burden and improved survival in this ovarian cancer model."( Anti-tumor activity of an anti-DR5 monoclonal antibody, TRA-8, in combination with taxane/platinum-based chemotherapy in an ovarian cancer model.
Amm, H; Bevis, KS; Buchsbaum, DJ; Della Manna, D; Londoño Joshi, A; McNally, LR; Sellers, JC; Straughn, JM, 2011)		0.37
" The aim of this study is to evaluate the efficacy and side effects of pemetrexed combined with cisplatin/carboplatin in the treatment of advanced recurrent or metastasis NSCLC."( [Pemetrexed combined with cisplatin or carboplatin regimen in the treatment of advanced recurrent or metastasis non-small cell lung cancer: analysis of 63 cases].
Li, J; Li, X; Liu, J; Shang, L; Wang, W; Wen, F, 2011)		0.37
"Pemetrexed combined with cisplatin/carboplatin is effective and feasible for advanced recurrent or metastasis NSCLC."( [Pemetrexed combined with cisplatin or carboplatin regimen in the treatment of advanced recurrent or metastasis non-small cell lung cancer: analysis of 63 cases].
Li, J; Li, X; Liu, J; Shang, L; Wang, W; Wen, F, 2011)		0.37
" This phase II study was designed to evaluate the toxicity and efficacy of belotecan combined with carboplatin in patients with recurrent epithelial ovarian cancer (EOC)."( Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer.
Bae, DS; Choi, CH; Kim, BG; Kim, MK; Kim, TJ; Lee, JH; Lee, JW; Lee, YY; Park, HS; Song, TJ, 2011)		0.37
"The newly developed topoisomerase I inhibitor belotecan (CKD-602) combined with carboplatin is a well-tolerated regimen with activity in recurrent EOC."( Phase II study of belotecan, a camptothecin analogue, in combination with carboplatin for the treatment of recurrent ovarian cancer.
Bae, DS; Choi, CH; Kim, BG; Kim, MK; Kim, TJ; Lee, JH; Lee, JW; Lee, YY; Park, HS; Song, TJ, 2011)		0.37
"TLF, in combination with C/P, demonstrated an apparent improvement in RR, PFS, and OS in patients with previously untreated stage IIIB/IV non-small cell lung cancer and appears to enhance activity without significant additional toxicity."( A randomized, double-blind, placebo-controlled, phase II study of oral talactoferrin in combination with carboplatin and paclitaxel in previously untreated locally advanced or metastatic non-small cell lung cancer.
Advani, SH; Bapna, A; Digumarti, R; Doval, DC; Julka, PK; Madhavan, J; Malik, R; Nag, S; Parikh, PM; Patil, S; Raman, G; Ranade, AA; Varadhachary, A; Wang, Y, 2011)		0.37
"Patients with ROC after first- or second-line treatment including a platinum and taxane and progression within 6 months were randomized to weekly paclitaxel (wP, 80 mg/m(2)/week) alone or in combination with carboplatin (C, area under the curve of 5 mg/ml/min every 4 weeks) or weekly topotecan (wT, 3 mg/m(2)/week)."( Weekly paclitaxel as a single agent or in combination with carboplatin or weekly topotecan in patients with resistant ovarian cancer: the CARTAXHY randomized phase II trial from Groupe d'Investigateurs Nationaux pour l'Etude des Cancers Ovariens (GINECO).
Alexandre, J; Dauba, J; Durando, X; Gladieff, L; Largillier, R; Lortholary, A; Paraiso, D; Pujade-Lauraine, E; Slama, B; Weber, B, 2012)		0.38
"gov: NCT00603538) assessed the safety and tolerability of figitumumab (6, 10 and 20 mg/kg) in combination with carboplatin (area under the curve: 6 mg·min/mL) and paclitaxel (200 mg/m(2)) in Japanese patients (N = 19) with chemotherapy-naïve, advanced NSCLC."( Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer.
Asahina, H; Goto, Y; Kikkawa, H; Kunitoh, H; Nokihara, H; Ohe, Y; Ohki, E; Sekine, I; Shibata, T; Tamura, T; Tanai, C; Tanioka, M; Yamamoto, N, 2012)		0.38
"Figitumumab in combination with carboplatin and paclitaxel was well tolerated at doses up to 20 mg/kg; no dose-limiting toxicities were observed at this dose level."( Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer.
Asahina, H; Goto, Y; Kikkawa, H; Kunitoh, H; Nokihara, H; Ohe, Y; Ohki, E; Sekine, I; Shibata, T; Tamura, T; Tanai, C; Tanioka, M; Yamamoto, N, 2012)		0.38
"Figitumumab 20 mg/kg in combination with carboplatin and paclitaxel was well tolerated in chemotherapy-naïve Japanese patients with NSCLC."( Figitumumab combined with carboplatin and paclitaxel in treatment-naïve Japanese patients with advanced non-small cell lung cancer.
Asahina, H; Goto, Y; Kikkawa, H; Kunitoh, H; Nokihara, H; Ohe, Y; Ohki, E; Sekine, I; Shibata, T; Tamura, T; Tanai, C; Tanioka, M; Yamamoto, N, 2012)		0.38
"To evaluate the efficacy and safety of dulanermin combined with paclitaxel and carboplatin (PC) and bevacizumab (PCB) as first-line treatment for advanced or recurrent non-small-cell lung cancer (NSCLC)."( Randomized phase II study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer.
Albert, I; Amler, L; Ashkenazi, A; Baker, N; Blackhall, F; Hei, YJ; Juhász, E; Kozielski, J; Márk, Z; Pan, Y; Pujol, JL; Smethurst, D; Soria, JC; Stern, H; Szima, B; Zatloukal, P, 2011)		0.37
" Pemetrexed in combination with carboplatin has been shown to be feasible in a phase I study in PSOC."( A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer.
Alvarez, AM; Bauknecht, T; Ghatage, P; Look, KY; Manouchehrpour, S; Oskay-Öezcelik, G; Sehouli, J; Szczylik, C; Zimmermann, A, 2012)		0.38
" Defining the platinum-based combination with the best therapeutic index would require a prospective phase III study."( A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer.
Alvarez, AM; Bauknecht, T; Ghatage, P; Look, KY; Manouchehrpour, S; Oskay-Öezcelik, G; Sehouli, J; Szczylik, C; Zimmermann, A, 2012)		0.38
" An open-label, single-arm, phase I study was performed to evaluate escalating doses of TSU-68 in combination with standard chemotherapy in patients with advanced non-small cell lung cancer."( Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer.
Hokoda, N; Kasahara, K; Kitamura, R; Miyazaki, M; Nakagawa, K; Nakayama, H; Ohyama, A; Okamoto, I; Satouchi, M; Seto, T; Takeda, K; Yamamoto, N; Yoshihara, E; Yoshioka, H, 2012)		0.38
"Eligible patients received TSU-68 at 200 or 400 mg twice daily and continuously in combination with carboplatin (area under the curve, 6 mg · min/mL) plus paclitaxel (200 mg/m2) on day 1 every 21 days."( Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer.
Hokoda, N; Kasahara, K; Kitamura, R; Miyazaki, M; Nakagawa, K; Nakayama, H; Ohyama, A; Okamoto, I; Satouchi, M; Seto, T; Takeda, K; Yamamoto, N; Yoshihara, E; Yoshioka, H, 2012)		0.38
"TSU-68 can be safely combined with standard doses of carboplatin-paclitaxel, with the combination manifesting promising antitumor activity."( Phase I clinical study of the angiogenesis inhibitor TSU-68 combined with carboplatin and paclitaxel in chemotherapy-naive patients with advanced non-small cell lung cancer.
Hokoda, N; Kasahara, K; Kitamura, R; Miyazaki, M; Nakagawa, K; Nakayama, H; Ohyama, A; Okamoto, I; Satouchi, M; Seto, T; Takeda, K; Yamamoto, N; Yoshihara, E; Yoshioka, H, 2012)		0.38
"To compare the efficacy, side effects and influence of two chemotherapy regimens, paclitaxel liposome combined with platinum and paclitaxel combined with platinum, on the survival rate in patients with cervical carcinoma receiving concurrent chemoradiotherapy."( [A randomized controlled trial of two chemotherapy regimens (paclitaxel liposome combined with platinum and paclitaxel combined with platinum) in concurrent chemoradiotherapy for cervical carcinoma].
Jiang, W; Li, L; Liu, Y; Wu, YY; Zeng, SY; Zhong, ML, 2011)		0.37
" We evaluated these novel retinoids in combination with chemotherapy against ovarian cancer stem cells (CSCs) in vitro and in an ex vivo model."( The impact of novel retinoids in combination with platinum chemotherapy on ovarian cancer stem cells.
Atigadda, VR; Buchsbaum, DJ; Londoño-Joshi, AI; Muccio, DD; Oliver, PJ; Sellers, JC; Straughn, JM; Whitworth, JM, 2012)		0.38
"Although zoledronic acid (ZOL) has been reported to inhibit bone metastasis from lung cancer, the optimum chemotherapy regimen in combination with ZOL has not yet been determined."( A feasibility study of zoledronic acid combined with carboplatin/nedaplatin plus paclitaxel in patients with non-small cell lung cancer with bone metastases.
Adachi, M; Hirama, M; Hirose, T; Ishiwata, T; Iwakami, S; Miura, K; Takahashi, K; Tominaga, S, )		0.13
"Eighteen patients having non-small cell lung cancer (NSCLC) with bone metastasis who received carboplatin/nedaplatin plus paclitaxel combined with ZOL (4 mg every 28 days) were enrolled to investigate the feasibility of this treatment."( A feasibility study of zoledronic acid combined with carboplatin/nedaplatin plus paclitaxel in patients with non-small cell lung cancer with bone metastases.
Adachi, M; Hirama, M; Hirose, T; Ishiwata, T; Iwakami, S; Miura, K; Takahashi, K; Tominaga, S, )		0.13
"ZOL combined with carboplatin/nedaplatin plus paclitaxel is an effective and tolerable treatment for NSCLC with bone metastases."( A feasibility study of zoledronic acid combined with carboplatin/nedaplatin plus paclitaxel in patients with non-small cell lung cancer with bone metastases.
Adachi, M; Hirama, M; Hirose, T; Ishiwata, T; Iwakami, S; Miura, K; Takahashi, K; Tominaga, S, )		0.13
" This trial tested custirsen (OGX-011), an inhibitor of CLU protein production, combined with gemcitabine/platinum in patients with advanced non-small cell lung cancer (NSCLC)."( Phase I/II trial of custirsen (OGX-011), an inhibitor of clusterin, in combination with a gemcitabine and platinum regimen in patients with previously untreated advanced non-small cell lung cancer.
Cormier, Y; Gitlitz, B; Gleave, ME; Hao, D; Laskin, JJ; Lee, C; Murray, N; Nemunaitis, J; Nicholas, G; Nugent, F; Pressnail, B; Sanborn, R; Stephenson, J; Ung, Y; Vincent, M, 2012)		0.38
" Custirsen was infused during a loading dose period and weekly in combination with gemcitabine (1250 mg/m) on days 1 and 8 and with cisplatin (75 mg/m) or carboplatin (area under the curve 5) on day 1 of each 21-day cycle."( Phase I/II trial of custirsen (OGX-011), an inhibitor of clusterin, in combination with a gemcitabine and platinum regimen in patients with previously untreated advanced non-small cell lung cancer.
Cormier, Y; Gitlitz, B; Gleave, ME; Hao, D; Laskin, JJ; Lee, C; Murray, N; Nemunaitis, J; Nicholas, G; Nugent, F; Pressnail, B; Sanborn, R; Stephenson, J; Ung, Y; Vincent, M, 2012)		0.38
"Twenty-five Chinese patients with advanced non-squamous NSCLC received bevacizumab (15 mg/kg) combined with chemotherapy (carboplatin plus paclitaxel) treatment from August 2007 to February 2008."( [Evaluation of efficacy and safety of bevacizumab combined with chemotherapy for Chinese patients with advanced non-small cell lung cancer].
Li, L; Wang, M; Zhang, L; Zhao, X; Zhong, W, 2012)		0.38
"Bevacizumab combined with carboplatin-based chemotherapy may be well tolerated and beneficial for Chinese patients with non-squamous NSCLC."( [Evaluation of efficacy and safety of bevacizumab combined with chemotherapy for Chinese patients with advanced non-small cell lung cancer].
Li, L; Wang, M; Zhang, L; Zhao, X; Zhong, W, 2012)		0.38
"Patients were randomly assigned to the control arm (PC) involving two cycles of induction paclitaxel 225 mg/m(2) and carboplatin area under the curve (AUC) 6 followed by 60 Gy thoracic radiation administered concurrently with weekly paclitaxel 45 mg/m(2) and carboplatin AUC 2, or to the experimental arm (TPC), receiving the same treatment in combination with thalidomide at a starting dose of 200 mg daily."( Randomized phase III study of thoracic radiation in combination with paclitaxel and carboplatin with or without thalidomide in patients with stage III non-small-cell lung cancer: the ECOG 3598 study.
Belinsky, SA; Dahlberg, SE; Fitzgerald, TJ; Hoang, T; Johnson, DH; Mehta, MP; Schiller, JH, 2012)		0.38
" RT3D shows synergistic in vitro cytotoxicity in combination with platins and taxanes."( Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies.
Ball, M; Chester, J; Coffey, M; Gore, ME; Hall, GD; Harrington, KJ; Karapanagiotou, EM; Larkin, J; Melcher, AA; Mettinger, K; Newbold, K; Nutting, C; Pandha, HS; Roulstone, V; Syrigos, KN; Tanay, M; Thompson, B; Twigger, K; Vile, RG, 2012)		0.38
" A phase I trial was conducted to evaluate the safety of obatoclax, a Bcl-2 family inhibitor, given in combination with standard chemotherapy."( A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer.
Berger, MS; Blakely, J; Chiappori, AA; Chu, QS; Moezi, MM; Ross, HJ; Salgia, R; Schnyder, J; Schreeder, MT; Stephenson, JJ; Subramaniam, DS, 2012)		0.38
" Patients were treated with escalating doses of obatoclax, either as a 3- or 24-h infusion, on days 1-3 of a 21-day cycle, in combination with carboplatin (area under the curve 5, day 1 only) and etoposide (100 mg m(-2), days 1-3)."( A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer.
Berger, MS; Blakely, J; Chiappori, AA; Chu, QS; Moezi, MM; Ross, HJ; Salgia, R; Schnyder, J; Schreeder, MT; Stephenson, JJ; Subramaniam, DS, 2012)		0.38
"Although associated with a higher incidence of transient CNS AEs than the 24-h infusion, 3-h obatoclax infusion combined with carboplatin-etoposide was generally well tolerated at doses of 30 mg per day."( A phase I trial of pan-Bcl-2 antagonist obatoclax administered as a 3-h or a 24-h infusion in combination with carboplatin and etoposide in patients with extensive-stage small cell lung cancer.
Berger, MS; Blakely, J; Chiappori, AA; Chu, QS; Moezi, MM; Ross, HJ; Salgia, R; Schnyder, J; Schreeder, MT; Stephenson, JJ; Subramaniam, DS, 2012)		0.38
"To analyze the efficacy and quality of life and safety for paclitaxel and carboplatin (TC) and TC combined with endostar in the treatment of advanced non-small cell lung cancer (NSCLC)."( [A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].
Bai, CX; Gu, AQ; Guo, SL; Han, BH; Jiang, LY; Jin, B; Jin, XQ; Liu, WC; Luo, Y; Shen, J; Shi, CL; Wang, HM; Xiu, QY; Zhang, Y; Zhao, YZ; Zhou, JY; Zhuang, ZX, 2011)		0.37
"The objective response rate (ORR) of TC combined with endostar arm was 39."( [A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].
Bai, CX; Gu, AQ; Guo, SL; Han, BH; Jiang, LY; Jin, B; Jin, XQ; Liu, WC; Luo, Y; Shen, J; Shi, CL; Wang, HM; Xiu, QY; Zhang, Y; Zhao, YZ; Zhou, JY; Zhuang, ZX, 2011)		0.37
"Compared with TC alone treatmrnt, TC combined with endostar treatment can reduce the risk of disease progression at early time (24 weeks), increase the ORR, and can be used as first-line treatment for advanced NSCLC."( [A multicenter, randomized, double-blind, placebo-controlled safety study to evaluate the clinical effects and quality of life of paclitaxel-carboplatin (PC) alone or combined with endostar for advanced non-small cell lung cancer (NSCLC)].
Bai, CX; Gu, AQ; Guo, SL; Han, BH; Jiang, LY; Jin, B; Jin, XQ; Liu, WC; Luo, Y; Shen, J; Shi, CL; Wang, HM; Xiu, QY; Zhang, Y; Zhao, YZ; Zhou, JY; Zhuang, ZX, 2011)		0.37
"To observe the correlation between long term efficacy/safety and treatment cycles of rh-endostatin (endostar) combined with TP (paclitaxel plus cisplatin/carboplatin) or NP (navelbine plus cisplatin/carboplatin) regimens in patients with advanced non-small cell lung cancer (NSCLC)."( [Efficacy of endostar combined with chemotherapy in multi-cycle treatment of patients with advanced non-small cell lung cancer].
Jin, ZL; Li, K; Li, N; Liu, ZJ; Wang, J, 2011)		0.37
" Twenty-one patients underwent endostar combined with NP regimen and other four patients underwent endostar combined with TP regimen (all repeated 21 days) treatment."( [Efficacy of endostar combined with chemotherapy in multi-cycle treatment of patients with advanced non-small cell lung cancer].
Jin, ZL; Li, K; Li, N; Liu, ZJ; Wang, J, 2011)		0.37
"Endostar combined with TP or NP regimen chemotherapy is effective and safe in the treatment of advanced NSCLC, especially in patients with long term treatment cycles which can effectively prolong TTP and reach long term survival, but not increase adverse events."( [Efficacy of endostar combined with chemotherapy in multi-cycle treatment of patients with advanced non-small cell lung cancer].
Jin, ZL; Li, K; Li, N; Liu, ZJ; Wang, J, 2011)		0.37
" This phase I, open-label dose-escalation study investigated BIBF 1120 combined with paclitaxel (Taxol) and carboplatin in first-line patients with advanced (IIIB/IV) non-small-cell lung cancer."( A phase I, open-label dose-escalation study of continuous treatment with BIBF 1120 in combination with paclitaxel and carboplatin as first-line treatment in patients with advanced non-small-cell lung cancer.
Camidge, DR; Conkling, P; Doebele, RC; Kaiser, R; Otterson, GA; Stopfer, P; Traynor, AM; Wind, S; Zhao, Y, 2012)		0.38
" in combination with paclitaxel and carboplatin."( A phase I, open-label dose-escalation study of continuous treatment with BIBF 1120 in combination with paclitaxel and carboplatin as first-line treatment in patients with advanced non-small-cell lung cancer.
Camidge, DR; Conkling, P; Doebele, RC; Kaiser, R; Otterson, GA; Stopfer, P; Traynor, AM; Wind, S; Zhao, Y, 2012)		0.38
"d when given with paclitaxel and carboplatin; this combination demonstrated an acceptable safety profile."( A phase I, open-label dose-escalation study of continuous treatment with BIBF 1120 in combination with paclitaxel and carboplatin as first-line treatment in patients with advanced non-small-cell lung cancer.
Camidge, DR; Conkling, P; Doebele, RC; Kaiser, R; Otterson, GA; Stopfer, P; Traynor, AM; Wind, S; Zhao, Y, 2012)		0.38
" The purpose of this study was to determine the maximally tolerated dose, peak plasma concentrations and side effect profile of oral rosiglitazone when combined with carboplatin in dogs with cancer."( Phase I clinical trial of oral rosiglitazone in combination with intravenous carboplatin in cancer-bearing dogs.
Allstadt Frazier, S; Guerrero, TA; Kass, PH; LaChapelle, H; McKemie, DS; Rodriguez, CO; Skorupski, KA, 2014)		0.4
"As a prelude to combination studies aimed at resistance reversal, this dose-escalation/dose-expansion study investigated the selective Src kinase inhibitor saracatinib (AZD0530) in combination with carboplatin and/or paclitaxel."( Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or carboplatin in patients with solid tumours.
Aamdal, S; Barrett, S; Barriuso, J; Boven, E; Burke, W; de Vries, EG; Emeribe, U; Freyer, G; Hartog, V; Jones, R; Kaye, S; Kristensen, GB; Kuenen, B; Nyakas, M; Pietersma, D; Pujade-Lauraine, E; Ruijter, R; Sandhu, S; Stuart, M; Tan, DS, 2012)		0.38
"Patients with advanced solid tumours received saracatinib once-daily oral tablets in combination with either carboplatin AUC 5 every 3 weeks (q3w), paclitaxel 175 mg m(-2) q3w, paclitaxel 80 mg m(-2) every 1 week (q1w), or carboplatin AUC 5 plus paclitaxel 175 mg m(-2) q3w."( Phase I study of saracatinib (AZD0530) in combination with paclitaxel and/or carboplatin in patients with solid tumours.
Aamdal, S; Barrett, S; Barriuso, J; Boven, E; Burke, W; de Vries, EG; Emeribe, U; Freyer, G; Hartog, V; Jones, R; Kaye, S; Kristensen, GB; Kuenen, B; Nyakas, M; Pietersma, D; Pujade-Lauraine, E; Ruijter, R; Sandhu, S; Stuart, M; Tan, DS, 2012)		0.38
"This study aimed to establish the maximum tolerated dose (MTD) of weekly bortezomib in combination with fixed standard doses of carboplatin and bevacizumab, and to estimate the efficacy (response rate and progression free survival [PFS]) and safety of combination therapy with carboplatin, bortezomib, and bevacizumab as first-line therapy in patients with advanced non-small-cell lung cancer (NSCLC)."( Phase-I/II study of bortezomib in combination with carboplatin and bevacizumab as first-line therapy in patients with advanced non-small-cell lung cancer.
Bathini, V; Bradley, K; Hanrahan-Boshes, M; Hutchinson, L; Perez-Soler, R; Piperdi, B; Walsh, WV; Zhou, Z, 2012)		0.38
"8 mg/m weekly on day 1 and day 8 in combination with carboplatin AUC 6 and bevacizumab 15 mg/kg on every 21-day cycle."( Phase-I/II study of bortezomib in combination with carboplatin and bevacizumab as first-line therapy in patients with advanced non-small-cell lung cancer.
Bathini, V; Bradley, K; Hanrahan-Boshes, M; Hutchinson, L; Perez-Soler, R; Piperdi, B; Walsh, WV; Zhou, Z, 2012)		0.38
"From September 2008 to October 2011, a total of 31 patients of NSCLC with multiple brain metastases (≥3) received selected incranial, bronchial and corresponding target arterial infusion chemotherapy combined with EGFR-TKIs."( [Selected arterial infusion chemotherapy combined with target drugs for non-small cell lung cancer with multiple brain metastase].
Guo, Z; Li, J, 2012)		0.38
" This 3 + 3 dose-escalation phase I study evaluated the maximum-tolerated regimen (MTR) of daily pazopanib in combination with paclitaxel 175 mg/m(2) and carboplatin [dosed at area under the curve (AUC) 5 or 6] given every 21 days in patients with advanced solid tumors."( Phase I study of pazopanib in combination with paclitaxel and carboplatin given every 21 days in patients with advanced solid tumors.
Ball, HA; Burris, HA; Dar, MM; Dowlati, A; Gainer, SD; Infante, JR; Jones, SF; Levinson, KT; Lindquist, D; Moss, RA; Spigel, DR; Suttle, AB; Tan, AR, 2012)		0.38
" We propose to define the recommended dose (RD) of VFL in combination with carboplatin in advanced NSCLC patients."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012)		0.38
"This phase I and pharmacokinetic study was designed to determine the maximum tolerated dose and to establish the RD of VFL in combination with carboplatin."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012)		0.38
" The RD was established at the dose of VFL (320 mg/m(2)) combined with carboplatin AUC5."( Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.
Ferre, P; Pinel, MC; Robinet, G; Tourani, JM; Tournoux-Facon, C, 2012)		0.38
"Paclitaxel in combination with carboplatin demonstrated acceptable levels of toxicity, but it was not active in the treatment of recurrent or progressive uterine sarcoma."( Phase II study of paclitaxel in combination with carboplatin for patients with recurrent or persistent uterine sarcoma.
Kang, S; Lim, MC; Lim, S; Park, JY; Park, SY; Seo, SS; Yoo, HJ, 2012)		0.38
"We conducted a phase I study of dasatinib, an oral SRC-family tyrosine kinase inhibitor, in combination with paclitaxel and carboplatin in the treatment of advanced and recurrent epithelial ovarian cancer."( A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer.
Barry, WT; Berchuck, A; Broadwater, G; Havrilesky, LJ; Lancaster, J; Lee, PS; Secord, AA; Teoh, DK; Wenham, RM; Yu, M, 2012)		0.38
"Due to the high incidence of myelosuppression with subsequent cycles, the recommended phase II dose of dasatinib is 150 mg daily in combination with paclitaxel and carboplatin."( A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer.
Barry, WT; Berchuck, A; Broadwater, G; Havrilesky, LJ; Lancaster, J; Lee, PS; Secord, AA; Teoh, DK; Wenham, RM; Yu, M, 2012)		0.38
"To evaluate in vitro effects of gemcitabine alone and in combination with carboplatin on canine transitional cell carcinoma (TCC) cell lines."( Effects of gemcitabine and gemcitabine in combination with carboplatin on five canine transitional cell carcinoma cell lines.
Chew, DJ; de Brito Galvao, JF; Inpanbutr, N; Kisseberth, WC; Murahari, S; Sutayatram, S, 2012)		0.38
"To determine the maximum tolerated doses and dose-limiting toxicities of oral panobinostat in combination with paclitaxel and carboplatin when administered to patients with advanced solid tumors."( A phase I trial of oral administration of panobinostat in combination with paclitaxel and carboplatin in patients with solid tumors.
Bendell, JC; Burris, HA; Infante, JR; Jones, SF; Mohyuddin, A; Thompson, DS; Yardley, DA, 2012)		0.38
"The recommended phase II dose is panobinostat 10 mg orally three times weekly in combination with paclitaxel 175 mg/m(2) and carboplatin AUC 5 administered intravenously on day 1 of every 21-day cycle."( A phase I trial of oral administration of panobinostat in combination with paclitaxel and carboplatin in patients with solid tumors.
Bendell, JC; Burris, HA; Infante, JR; Jones, SF; Mohyuddin, A; Thompson, DS; Yardley, DA, 2012)		0.38
"This phase Ib study evaluated volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin (Eli Lilly and Co."( Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer.
Almokadem, S; Belani, CP; Besse, B; Chao, DT; Fang, Y; Soria, JC; Tsao, LC, 2013)		0.39
"Three cohorts were treated with volociximab (10, 20, or 30 mg/kg) for up to six 3-week cycles in combination with carboplatin-paclitaxel chemotherapy and continued as maintenance therapy for patients with stable disease (SD) or better."( Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer.
Almokadem, S; Belani, CP; Besse, B; Chao, DT; Fang, Y; Soria, JC; Tsao, LC, 2013)		0.39
"Volociximab combined with carboplatin and paclitaxel was generally well-tolerated and showed preliminary evidence of efficacy in advanced NSCLC."( Phase Ib safety and pharmacokinetic study of volociximab, an anti-α5β1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer.
Almokadem, S; Belani, CP; Besse, B; Chao, DT; Fang, Y; Soria, JC; Tsao, LC, 2013)		0.39
"Many studies have investigated the efficacy of Endostar combined with platinum-based doublet chemotherapy (PBDC) versus PBDC alone for treating advanced non-small cell lung cancer (NSCLC)."( Systematic review and meta-analysis of Endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer.
Li, W; Ming, Z; Rong, B; Yang, S; Zhang, W, 2012)		0.38
"Fifteen studies reporting Endostar combined with PBDC versus PBDC alone for treating advanced NSCLC were reviewed."( Systematic review and meta-analysis of Endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer.
Li, W; Ming, Z; Rong, B; Yang, S; Zhang, W, 2012)		0.38
"The overall response rate (ORR) and disease control rate (DCR) of Endostar combined with PBDC for treating NSCLC were significantly higher than those of PBDC alone, with 14."( Systematic review and meta-analysis of Endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer.
Li, W; Ming, Z; Rong, B; Yang, S; Zhang, W, 2012)		0.38
"Endostar combined with PBDC was associated with higher RR, DCR, and TTP as well as superior QOL profiles compared with PBDC alone."( Systematic review and meta-analysis of Endostar (rh-endostatin) combined with chemotherapy versus chemotherapy alone for treating advanced non-small cell lung cancer.
Li, W; Ming, Z; Rong, B; Yang, S; Zhang, W, 2012)		0.38
"This phase I dose-finding trial evaluated safety, efficacy and pharmacokinetics of axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors, combined with platinum doublets in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumours."( Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.
Arriola, E; Cohen, RB; De Castro Carpeño, J; Herbst, RS; Kim, S; Kozloff, MF; Krzakowski, M; Martin, LP; Olszanski, AJ; Rado, TA; Rosbrook, B; Samuel, TA; Tarazi, J; Tortorici, M, 2012)		0.38
" may be combined with standard paclitaxel/carboplatin or gemcitabine/cisplatin regimens without evidence of overt drug-drug interactions."( Phase I trial of axitinib combined with platinum doublets in patients with advanced non-small cell lung cancer and other solid tumours.
Arriola, E; Cohen, RB; De Castro Carpeño, J; Herbst, RS; Kim, S; Kozloff, MF; Krzakowski, M; Martin, LP; Olszanski, AJ; Rado, TA; Rosbrook, B; Samuel, TA; Tarazi, J; Tortorici, M, 2012)		0.38
" Animals that received carboplatin in combination with X-irradiation had a MeST of > 180 days with a 55% cure rate, irrespective of whether they were irradiated with either 78."( Intracerebral delivery of carboplatin in combination with either 6 MV photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma.
Adam, JF; Balosso, J; Barth, RF; Bobyk, L; Deman, P; Edouard, M; Elleaume, H; Estève, F; Ravanat, JL; Rousseau, J, 2012)		0.38
" delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays."( Intracerebral delivery of carboplatin in combination with either 6 MV photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma.
Adam, JF; Balosso, J; Barth, RF; Bobyk, L; Deman, P; Edouard, M; Elleaume, H; Estève, F; Ravanat, JL; Rousseau, J, 2012)		0.38
" This phase II study was conducted by the SWOG cooperative group to evaluate the efficacy of sorafenib in combination with carboplatin and paclitaxel (CP) in metastatic uveal melanoma."( Phase II trial of sorafenib in combination with carboplatin and paclitaxel in patients with metastatic uveal melanoma: SWOG S0512.
Aparicio, AM; Bhatia, S; Lao, CD; Margolin, KA; Moon, J; Othus, M; Ribas, A; Sondak, VK; Weber, JS, 2012)		0.38
"To evaluate the therapeutic efficacy of sorafenib in combination with microwave coagulation therapy (MCT) and trans-arterial chemoembolization (TACE) in patients with recurrent liver cancer."( [Therapeutic effects of sorafenib combined with transcatheter arterial chemoembolization and microwave ablation on postsurgical recurrent hepatocellular carcinoma].
He, ZY; Hua, XD, 2012)		0.38
"Sorafenib combined with MCT and TACE can improve the disease control rate and prolong the survival in patients with recurrent HCC."( [Therapeutic effects of sorafenib combined with transcatheter arterial chemoembolization and microwave ablation on postsurgical recurrent hepatocellular carcinoma].
He, ZY; Hua, XD, 2012)		0.38
" Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma."( The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro.
Edris, WA; Gitelman, AI; Helfand, SC; Marley, K; Mata, JE; Medlock, J; Séguin, B, 2013)		0.39
"We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT)."( Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer - a retrospective single center analysis.
Bischof, M; Debus, J; Huber, PE; Lindel, K; Muenter, MW; Roeder, F; Saleh-Ebrahimi, L; Zwicker, F, 2013)		0.39
"We conducted a phase II study of dual-agent monoclonal antibody therapy consisting of cetuximab and bevacizumab in combination with paclitaxel and carboplatin chemotherapy in non-small-cell lung cancer."( Randomized phase II study of cetuximab and bevacizumab in combination with two regimens of paclitaxel and carboplatin in chemonaive patients with stage IIIB/IV non-small-cell lung cancer.
Bonomi, PD; Katz, TL; Lee, HJ; Mace, J; Mandanas, RA; Min, M; Olsen, M; Sheth, G; Youssoufian, H, 2013)		0.39
"Patients with stage IIIB/IV nonsquamous non-small-cell lung cancer randomly received cetuximab (400 mg/m initially, 250 mg/m weekly thereafter) plus bevacizumab (15 mg/kg) for six cycles combined with paclitaxel (200 mg/m) and carboplatin (area under the curve 6) for either six cycles (six-cycle arm) or the first three cycles (three-cycle arm) (one cycle = 3 weeks)."( Randomized phase II study of cetuximab and bevacizumab in combination with two regimens of paclitaxel and carboplatin in chemonaive patients with stage IIIB/IV non-small-cell lung cancer.
Bonomi, PD; Katz, TL; Lee, HJ; Mace, J; Mandanas, RA; Min, M; Olsen, M; Sheth, G; Youssoufian, H, 2013)		0.39
" Bortezomib, a proteasome inhibitor,markedly enhanced the cytotoxic effects of panobinostat combined with gemcitabine."( Identification of unique synergistic drug combinations associated with downexpression of survivin in a preclinical breast cancer model system.
Budman, DR; Calabro, A; Lesser, M; Rosen, L, 2012)		0.38
"The protease inhibitor bortezomib attenuates the action of NF-κB and has shown preclinical activity alone and in combination with chemotherapy."( A phase I trial of bortezomib in combination with epirubicin, carboplatin and capecitabine (ECarboX) in advanced oesophagogastric adenocarcinoma.
Eatock, MM; Gallagher, R; James, CR; Law, D; Millar, J; Morris, M; Napier, E; Purcell, C; Turkington, RC; Wilson, RH, 2014)		0.4
"6 mg m(-2) on days 1 and 8 from cycle 2 onwards) in combination with Epirubicin 50 mg m(-2) intravenously on day 1, Carboplatin AUC 5 day 1 and Capecitabine 625 mg m(-2) BD days 1-21 every 21 days (VECarboX regimen), in patients with advanced oesophagogastric adenocarcinoma."( A phase I trial of bortezomib in combination with epirubicin, carboplatin and capecitabine (ECarboX) in advanced oesophagogastric adenocarcinoma.
Eatock, MM; Gallagher, R; James, CR; Law, D; Millar, J; Morris, M; Napier, E; Purcell, C; Turkington, RC; Wilson, RH, 2014)		0.4
" We performed a multi-center phase II trial investigating the safety and efficacy of ofatumumab, a monoclonal antibody against CD20, combined with ICE or DHAP second-line therapy in patients with relapsed or refractory DLBCL, grade 3b follicular lymphoma, or transformed follicular lymphoma."( Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma.
Czuczman, MS; Edvardsen, K; Fayad, L; Fecteau, D; Fennessy, M; Henkel, K; Jewell, RC; Joyce, R; Kharfan-Dabaja, MA; Liao, Q; Lisby, S; Lossos, IS; Matasar, MJ; Moskowitz, CH; Rodriguez, MA; Shea, TC; Singh, RP; Spitzer, G, 2013)		0.39
"Pertuzumab (P) combined with trastuzumab (H)-based chemotherapy improves efficacy in early and advanced HER2-positive breast cancer."( Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).
Chia, S; Cortés, J; Eniu, A; Harvey, V; Hegg, R; Hickish, T; McNally, V; Ratnayake, J; Ross, G; Schneeweiss, A; Seo, JH; Tausch, C; Tsai, YF, 2013)		0.39
"A total of 285 patients with stage Ib2 and IIa2 cervical cancer were categorized into three groups, and received preoperative neoadjuvant chemotherapy combined with vaginal intracavitary irradiation, neoadjuvant chemotherapy alone or radiotherapy, respectively."( Comparison of clinical efficacy of three different neoadjuvant approaches (chemotherapy combined vaginal intracavitary irradiation, neoadjuvant chemotherapy alone or radiotherapy) combined with surgery for patients with stage Ib2 and IIa2 cervical cancer.
Fu, JH; Gao, Z; Ren, CC; Shi, YG, 2013)		0.39
"The objective of this study was to determine the maximum tolerated dose (MTD) and acute dose-limiting toxicities (DLTs) of intravenous carboplatin plus paclitaxel combined with intensity-modulated pelvic radiotherapy (pelvic IMRT) as an adjuvant treatment for early-stage cervical cancer patients with positive pelvic lymph nodes."( A phase I study of concurrent weekly carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy as an adjuvant treatment for early-stage cervical cancer patients with positive pelvic lymph nodes.
Isohashi, F; Ito, K; Kimura, T; Mabuchi, S; Ogata, T; Ogawa, K; Takahashi, R; Tsutui, T; Yokoi, T; Yoshioka, Y, 2013)		0.39
"This dose-finding study evaluated lenvatinib, an oral multitargeted receptor tyrosine kinase inhibitor, in combination with carboplatin/paclitaxel in chemotherapy-naïve non-small-cell lung cancer (NSCLC) patients."( Phase 1 study of lenvatinib combined with carboplatin and paclitaxel in patients with non-small-cell lung cancer.
Horai, T; Horiike, A; Koizumi, F; Koyama, N; Murakami, H; Nishio, K; Nishio, M; Nokihara, H; Takahashi, T; Tamura, T; Yamamoto, N; Yusa, W, 2013)		0.39
"The escalating doses and cycles of intraperitoneal phIL-12/PPC when combined with carboplatin/docetaxel chemotherapy in recurrent ovarian cancer patients were well tolerated and did not appear to exacerbate the side effects or attenuate the efficacy of the chemotherapy treatment."( Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer.
Alvarez, RD; Anwer, K; Chu, C; Fewell, JG; Kelly, FJ; Lewis, D, 2013)		0.39
"To observe the clinical efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer (NSCLC)."( [Efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer].
Shi, X; Yu, XM; Zhang, YP; Zhao, J, 2013)		0.39
" Thus, pemetrexed combined with carboplatin is an effective chemotherapeutic regimen for advanced NSCLC in elderly patients."( [Efficacy and safety of pemetrexed or gemcitabine combined with carboplatin as the first-line therapy in elderly patients with advanced non-small cell lung cancer].
Shi, X; Yu, XM; Zhang, YP; Zhao, J, 2013)		0.39
" Sequential treatment with azacitidine and valproic acid (VPA) in combination with carboplatin may overcome resistance to platinum-based therapy, and we conducted a phase I trial to assess safety, maximum tolerated dose (MTD), and clinical correlates."( Methylation and histone deacetylase inhibition in combination with platinum treatment in patients with advanced malignancies.
Bustinza-Linares, E; Falchook, GS; Fu, S; Hong, DS; Hu, W; Kurzrock, R; Moulder, S; Naing, A; Parkhurst, KL; Sood, AK; Wheler, JJ, 2013)		0.39
"To assess the efficacy and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced NSCLC."( Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.
da Silva, EM; de Castria, TB; Gois, AF; Riera, R, 2013)		0.39
"Randomised clinical trials comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC."( Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.
da Silva, EM; de Castria, TB; Gois, AF; Riera, R, 2013)		0.39
" Pharmacokinetic data revealed no clinically significant drug-drug interactions."( Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study.
Blais, N; Camidge, DR; Chao, RC; Chow, LQ; Diab, SG; Jonker, DJ; Laurie, SA; Ruiz-Garcia, A; Soulières, D; Thall, A; Zhang, K, 2013)		0.39
" We selected those patients for our study who were receiving treatment with paclitaxel, gemcitabine or etoposide in combination with platinum based drugs."( Survival analysis in advanced non small cell lung cancer treated with platinum based chemotherapy in combination with paclitaxel, gemcitabine and etoposide.
Jamil, K; Naidu Madireddy, UR; Natukula, K; Pingali, UR; Suresh Attili, VS, 2013)		0.39
" In the present analysis, we retrospectively investigated the feasibility and effectiveness of bevacizumab combined with ICE in patients with glioblastoma at second relapse during ICE treatment."( Retrospective analysis of bevacizumab in combination with ifosfamide, carboplatin, and etoposide in patients with second recurrence of glioblastoma.
Arakawa, Y; Fujimoto, K; Kikuchi, T; Kunieda, T; Miyamoto, S; Mizowaki, T; Murata, D; Takagi, Y; Takahashi, JC, 2013)		0.39
" The objective of this study was to investigate the antitumor effects of tigatuzumab combined with carboplatin/paclitaxel in chemotherapy-naïve patients with metastatic/unresectable non-small cell lung cancer (NSCLC)."( A randomized, double-blind, placebo-controlled phase 2 study of tigatuzumab (CS-1008) in combination with carboplatin/paclitaxel in patients with chemotherapy-naïve metastatic/unresectable non-small cell lung cancer.
Beckman, RA; Chmielowska, E; Fox, T; Greenberg, J; Hadler, D; Krzakowski, M; Reck, M; Sebastian, M; von Pawel, J; Wang, Q, 2013)		0.39
" Therefore, we conducted a phase II study of concurrent weekly carboplatin plus paclitaxel treatment in combination with radiotherapy followed by vinorelbine monotherapy."( Phase II study of concurrent thoracic radiotherapy in combination with weekly paclitaxel plus carboplatin in locally advanced non-small cell lung cancer: LOGIK0401.
Harada, T; Imanaga, T; Inoue, K; Kawasaki, M; Kuba, M; Matsumoto, T; Nakanishi, Y; Oshima, T; Shioyama, Y; Takayama, K; Takeshita, M; Tokunaga, S, 2013)		0.39
"To determine the maximum tolerated dose and the recommended dose (RD) for phase II trials of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine."( Phase I study of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine in patients with advanced malignancies.
Alexandre, J; Coronado, C; Dios, JL; Faivre, S; Fernández-García, EM; Goldwasser, F; Kahatt, CM; Miguel-Lillo, B; Paramio, PG; Raymond, E, 2014)		0.4
"Infra-optimal doses of elisidepsin and carboplatin and a lack of antitumor activity despite using active drug concentrations in combination with gemcitabine do not warrant further clinical development for these two combinations."( Phase I study of elisidepsin (Irvalec®) in combination with carboplatin or gemcitabine in patients with advanced malignancies.
Alexandre, J; Coronado, C; Dios, JL; Faivre, S; Fernández-García, EM; Goldwasser, F; Kahatt, CM; Miguel-Lillo, B; Paramio, PG; Raymond, E, 2014)		0.4
"First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED)."( Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors.
Agius, L; Barth, RF; Grecula, JC; Gupta, N; Huo, T; Nakkula, RJ; Weldon, M; Yang, W, 2014)		0.4
"Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less late tissue effects."( Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors.
Agius, L; Barth, RF; Grecula, JC; Gupta, N; Huo, T; Nakkula, RJ; Weldon, M; Yang, W, 2014)		0.4
"This study investigates the mechanism of action behind the long-term responses (12-16 months) of two BRAF WT melanoma patients to the AKT inhibitor MK-2206 in combination with paclitaxel and carboplatin."( Inhibition of autophagy enhances the effects of the AKT inhibitor MK-2206 when combined with paclitaxel and carboplatin in BRAF wild-type melanoma.
Amaravadi, RK; Anderson, AR; Fedorenko, IV; Gibney, GT; Kim, E; Kudchadkar, RR; Maria-Engler, SS; Massaro, RR; Messina, JL; Rebecca, VW; Smalley, KS; Sondak, VK, 2014)		0.4
" No pharmacokinetic drug-drug alterations occurred."( Phase I study of carboplatin in combination with PM00104 (Zalypsis®) in patients with advanced solid tumors.
Alfaro, V; Calles, A; Calvo, E; Coronado, C; Durán, I; Fernández-Teruel, C; García, M; Gil, M; Hidalgo, M; Prados, R; Salazar, R; Siguero, M, 2014)		0.4
"This phase II study examined the efficacy of mapatumumab in combination with paclitaxel and carboplatin in patients with non-small-cell lung cancer (NSCLC)."( Phase II trial of mapatumumab, a fully human agonist monoclonal antibody to tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1), in combination with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer.
Camidge, DR; Cebotaru, CL; Dediu, M; Fox, NL; Gribbin, MJ; Harvey, JH; Humphreys, RC; Reck, M; Spigel, DR; von Pawel, J, 2014)		0.4
"This study was designed to evaluate the response and toxicity of sorafenib alone or when combined with carboplatin and paclitaxel in patients with platinum-sensitive, recurrent ovarian cancer, fallopian tube cancer, or primary peritoneal cancer (EOC)."( Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer.
Dowlati, A; Eaton, S; Frasure, H; Fu, P; Fusco, N; Schwandt, A; von Gruenigen, VE; Waggoner, S; Wenham, RM; Wright, JJ, 2014)		0.4
"Sorafenib, alone or in combination with carboplatin and paclitaxel, has activity in patients with platinum-sensitive EOC."( Randomized phase II trial of sorafenib alone or in combination with carboplatin/paclitaxel in women with recurrent platinum sensitive epithelial ovarian, peritoneal, or fallopian tube cancer.
Dowlati, A; Eaton, S; Frasure, H; Fu, P; Fusco, N; Schwandt, A; von Gruenigen, VE; Waggoner, S; Wenham, RM; Wright, JJ, 2014)		0.4
"To observe the effects of poly(ADP-ribose)polymerase (PARP) inhibitor AG014699 alone and combined with docetaxel (DTX) or carboplatin (CBP) on the proliferation of triple-negative breast cancer cell line MDA-MB-231 and to investigate whether PARP inhibitor AG014699 combined with chemotherapy could play a synergistic antitumor effect."( [Effects of poly(ADP-ribose)polymerase inhibitor AG014699 combined with chemotherapy on the proliferation of triple-negative breast cancer cell line MDA-MB-231].
Ding, H; Li, L; Li, XQ; Sun, Y, 2014)		0.4
"MDA-MB-231 cells were treated by PARP inhibitor AG014699 alone or combination with DTX or CBP."( [Effects of poly(ADP-ribose)polymerase inhibitor AG014699 combined with chemotherapy on the proliferation of triple-negative breast cancer cell line MDA-MB-231].
Ding, H; Li, L; Li, XQ; Sun, Y, 2014)		0.4
"PARP inhibitor AG014699 combined with DTX or CBP can remarkably inhibit MDA-MB-231 cell proliferation, showing additive or synergistic antitumor effects."( [Effects of poly(ADP-ribose)polymerase inhibitor AG014699 combined with chemotherapy on the proliferation of triple-negative breast cancer cell line MDA-MB-231].
Ding, H; Li, L; Li, XQ; Sun, Y, 2014)		0.4
" This phase 1 dose-escalation study evaluated the pharmacokinetics, safety, and efficacy of linifanib in combination with carboplatin/paclitaxel in Japanese patients with advanced NSCLC."( A phase 1 study of linifanib in combination with carboplatin/paclitaxel as first-line treatment of Japanese patients with advanced or metastatic non-small cell lung cancer (NSCLC).
Carlson, DM; Horai, T; Horiike, A; Horinouchi, H; Kaneda, H; McKee, MD; Nakagawa, K; Nishio, M; Nokihara, H; Ohyanagi, F; Okabe, T; Tamura, T; Terashima, M; Xiong, H; Yamamoto, N, 2014)		0.4
" Linifanib Cmax occurred at 2-3 h with both doses and when given alone or in combination with carboplatin/paclitaxel."( A phase 1 study of linifanib in combination with carboplatin/paclitaxel as first-line treatment of Japanese patients with advanced or metastatic non-small cell lung cancer (NSCLC).
Carlson, DM; Horai, T; Horiike, A; Horinouchi, H; Kaneda, H; McKee, MD; Nakagawa, K; Nishio, M; Nokihara, H; Ohyanagi, F; Okabe, T; Tamura, T; Terashima, M; Xiong, H; Yamamoto, N, 2014)		0.4
"This is the first prospective study of AMR combined with CBDCA for refractory relapsed SCLC, which was effective and well tolerated."( Phase II study of amrubicin combined with carboplatin for refractory relapsed small-cell lung cancer: North Japan Lung Cancer Group Trial 0802.
Asahina, H; Harada, M; Hasegawa, Y; Inoue, A; Ishimoto, O; Kawashima, Y; Maemondo, M; Morikawa, N; Nukiwa, T; Oizumi, S; Okudera, K; Saito, R; Sakakibara, T; Sugawara, S; Suzuki, T; Usui, K, 2014)		0.4
" Primary endpoints assessed the safety and pharmacokinetic (PK) interactions between navitoclax in combination with carboplatin/paclitaxel or paclitaxel alone in patients with solid tumors The study comprised two arms, one a combination of navitoclax with paclitaxel and carboplatin, the second with navitoclax and paclitaxel alone."( A phase I safety and pharmacokinetic study of ABT-263 in combination with carboplatin/paclitaxel in the treatment of patients with solid tumors.
Busman, T; Cosgrove, D; Karantza, V; Mabry, M; Rudersdorf, N; Vlahovic, G; Wang, D; Xiong, H; Yang, J, 2014)		0.4
"To evaluate the curative effect and clinical application of hepatic arterial infusion (HAI) chemotherapy combined with endogenetic field tumor hyperthermia (EFTH) in patients with hilar cholangiocarcinoma."( Hepatic arterial infusion chemotherapy combined with endogenetic hyperthermia treatment of hilar cholangiocarcinoma.
Chen, YT; Sun, HL; Teng, H; Xu, LF; Yao, HR, )		0.13
"HAI chemotherapy combined with EFTH is safe, minimally invasive, and well tolerated."( Hepatic arterial infusion chemotherapy combined with endogenetic hyperthermia treatment of hilar cholangiocarcinoma.
Chen, YT; Sun, HL; Teng, H; Xu, LF; Yao, HR, )		0.13
" Ombrabulin was combined with two standard taxane/platinum doublets in a phase I study to determine the recommended combination doses."( Phase I clinical and pharmacokinetic study of ombrabulin (AVE8062) combined with cisplatin/docetaxel or carboplatin/paclitaxel in patients with advanced solid tumors.
Bahleda, R; Capri, G; Daglish, B; Del Conte, G; Gianni, L; Hospitel, M; Oprea, C; Sessa, C; Soria, JC; Varga, A, 2014)		0.4
" The aim of this study was to investigate the antitumor activity of recombinant human Apo2L/TRAIL (dulanermin) in combination with chemotherapy in MPM in vitro and in vivo."( Synergistic antitumor activity of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma.
Cavallari, I; Ciminale, V; Favaretto, A; Marulli, G; Nannini, N; Pasello, G; Rea, F; Schiavon, M; Silic-Benussi, M; Urso, L, 2014)		0.4
"In the present studies, we employed a panel of MPM cell lines to test the antitumor activity of recombinant human Apo2L/TRAIL (T) in combination with carboplatin and pemetrexed (CP) in vitro and SCID mice."( Synergistic antitumor activity of recombinant human Apo2L/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in combination with carboplatin and pemetrexed in malignant pleural mesothelioma.
Cavallari, I; Ciminale, V; Favaretto, A; Marulli, G; Nannini, N; Pasello, G; Rea, F; Schiavon, M; Silic-Benussi, M; Urso, L, 2014)		0.4
"The purpose of this study was to evaluate, retrospectively, the clinical efficacy of preoperative transcatheter arterial chemoembolization (TACE) combined with systemic chemotherapy for unresectable hepatoblastoma."( Efficacy of preoperative transcatheter arterial chemoembolization combined with systemic chemotherapy for treatment of unresectable hepatoblastoma in children.
Asayama, Y; Fujita, N; Hirakawa, M; Honda, H; Ishigami, K; Nishie, A; Taguchi, T; Tajiri, T, 2014)		0.4
"2 months) were treated with preoperative TACE combined with systemic chemotherapy for unresectable hepatoblastomas."( Efficacy of preoperative transcatheter arterial chemoembolization combined with systemic chemotherapy for treatment of unresectable hepatoblastoma in children.
Asayama, Y; Fujita, N; Hirakawa, M; Honda, H; Ishigami, K; Nishie, A; Taguchi, T; Tajiri, T, 2014)		0.4
" In all cases TACE combined with systemic chemotherapy enabled subsequent safe and complete surgical resection."( Efficacy of preoperative transcatheter arterial chemoembolization combined with systemic chemotherapy for treatment of unresectable hepatoblastoma in children.
Asayama, Y; Fujita, N; Hirakawa, M; Honda, H; Ishigami, K; Nishie, A; Taguchi, T; Tajiri, T, 2014)		0.4
"Preoperative TACE combined with systemic chemotherapy was effective in inducing surgical resectability of unresectable hepatoblastoma."( Efficacy of preoperative transcatheter arterial chemoembolization combined with systemic chemotherapy for treatment of unresectable hepatoblastoma in children.
Asayama, Y; Fujita, N; Hirakawa, M; Honda, H; Ishigami, K; Nishie, A; Taguchi, T; Tajiri, T, 2014)		0.4
" Carlumab could be safely administered at 10 or 15 mg/kg in combination with standard-of-care chemotherapy and was well-tolerated, although no long-term suppression of serum CCL2 or significant tumor responses were observed."( Carlumab, an anti-C-C chemokine ligand 2 monoclonal antibody, in combination with four chemotherapy regimens for the treatment of patients with solid tumors: an open-label, multicenter phase 1b study.
Brana, I; Calles, A; Calvo, E; de Boer, CJ; LoRusso, PM; Puchalski, TA; Seetharam, S; Tabernero, J; Yee, LK; Zhong, B, 2015)		0.42
" Treatment was administered with gemcitabine (1,000 mg/m(2) on days 1 and 8), cisplatin (70 mg/m(2)), or carboplatin (AUC 5) on day 1, and dovitinib (orally on days 1-5, 8-12, and 15-19), every 21 days."( Phase Ib study of dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin in patients with advanced solid tumors.
Galsky, MD; Gimpel-Tetra, K; Godbold, J; Holcombe, RF; Lee, KM; Lowe, N; Misiukiewicz, K; Oh, WK; Posner, M; Soto, R; Tsao, CK, 2014)		0.4
"Dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin was poorly tolerated due to myelosuppression."( Phase Ib study of dovitinib in combination with gemcitabine plus cisplatin or gemcitabine plus carboplatin in patients with advanced solid tumors.
Galsky, MD; Gimpel-Tetra, K; Godbold, J; Holcombe, RF; Lee, KM; Lowe, N; Misiukiewicz, K; Oh, WK; Posner, M; Soto, R; Tsao, CK, 2014)		0.4
"Platinum-based therapy combined with cetuximab is standard first-line therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMSCCHN)."( Phase 1 and pharmacokinetic study of everolimus in combination with cetuximab and carboplatin for recurrent/metastatic squamous cell carcinoma of the head and neck.
Beitler, JJ; Chen, AY; Chen, Z; El-Deiry, M; Harvey, D; Higgins, K; Hurwitz, SJ; Khuri, FR; Kim, S; Kono, SA; Lewis, C; Magliocca, K; Mendel, J; Owonikoko, TK; Ramalingam, SS; Rogerio, J; Saba, NF; Shin, DM; Sun, SY; Wadsworth, T, 2014)		0.4
"The effects of nilotinib on ovarian cancer cell growth were studied alone and in combination with carboplatin and paclitaxel."( Nilotinib in combination with carboplatin and paclitaxel is a candidate for ovarian cancer treatment.
Alkatout, I; Jonat, W; Maass, N; Mundhenke, C; Rath, K; Schem, C; Weigel, MT; Wenners, AS, 2014)		0.4
"Nilotinib alone and in combination with carboplatin and paclitaxel significantly inhibited cell growth in PDGFR-α-positive ovarian cancer cell lines."( Nilotinib in combination with carboplatin and paclitaxel is a candidate for ovarian cancer treatment.
Alkatout, I; Jonat, W; Maass, N; Mundhenke, C; Rath, K; Schem, C; Weigel, MT; Wenners, AS, 2014)		0.4
"The objective of this study was to determine whether the addition of ramucirumab to first-line paclitaxel-carboplatin chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) resulted in a 6-month progression-free survival (PFS) rate that compares favorably with the historic rate for bevacizumab combined with paclitaxel-carboplatin in this patient population."( A phase II, open-label study of ramucirumab in combination with paclitaxel and carboplatin as first-line therapy in patients with stage IIIB/IV non-small-cell lung cancer.
Ballas, MS; Berge, EM; Camidge, DR; Doebele, RC; Gao, L; Haigentz, M; Hoffman, D; Jahan, T; Joshi, A; Lee, P; Mita, A; Spicer, J; West, H; Yang, L; Yurasov, S, 2014)		0.4
"Ramucirumab in combination with paclitaxel-carboplatin resulted in a 6-month PFS rate and safety profile that compared favorably with the historical control."( A phase II, open-label study of ramucirumab in combination with paclitaxel and carboplatin as first-line therapy in patients with stage IIIB/IV non-small-cell lung cancer.
Ballas, MS; Berge, EM; Camidge, DR; Doebele, RC; Gao, L; Haigentz, M; Hoffman, D; Jahan, T; Joshi, A; Lee, P; Mita, A; Spicer, J; West, H; Yang, L; Yurasov, S, 2014)		0.4
"To explore the clinical efficacy and prognostic factors of chemoreduction combined with topical treatment of advanced intraocular retinoblastoma (RB)."( Clinical efficacy and prognostic factors of chemoreduction combined with topical treatment for advanced intraocular retinoblastoma.
Liu, F; Liu, Y; Wang, KL; Zhang, X, 2014)		0.4
"A total of 22 eyes from 17 children with RB were selected for the study and treated with chemoreduction combined with topical cryotherapy, transpupillary thermotherapy (TTT) or episcleral plaque brachytherapy."( Clinical efficacy and prognostic factors of chemoreduction combined with topical treatment for advanced intraocular retinoblastoma.
Liu, F; Liu, Y; Wang, KL; Zhang, X, 2014)		0.4
"8 courses on average); 17 eyes from 13 children were treated by chemoreduction combined with cryotherapy or TTT and 5 eyes from 4 children with chemoreduction combined with 125I episcleral plaque brachytherapy."( Clinical efficacy and prognostic factors of chemoreduction combined with topical treatment for advanced intraocular retinoblastoma.
Liu, F; Liu, Y; Wang, KL; Zhang, X, 2014)		0.4
"Chemoreduction combined with topical therapy can effectively control RB in the short term, and tumor basal diameter before treatment is an independent risk factor for prognosis."( Clinical efficacy and prognostic factors of chemoreduction combined with topical treatment for advanced intraocular retinoblastoma.
Liu, F; Liu, Y; Wang, KL; Zhang, X, 2014)		0.4
" The safety profile of trastuzumab in combination with carboplatin and docetaxel was consistent with the known safety profile of this combination."( Trastuzumab, in combination with carboplatin and docetaxel, does not prolong the QT interval of patients with HER2-positive metastatic or locally advanced inoperable solid tumors: results from a phase Ib study.
Eppler, S; Gordon, M; Lum, BL; Redfern, CH; Trudeau, C; Xu, N, 2014)		0.4
" This phase 2 study investigated ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in advanced/metastatic NSCLC."( Phase 2, randomized, open-label study of ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in patients with nonsquamous, advanced/metastatic non-small cell lung cancer.
Alexandris, E; Bonomi, P; Bustin, F; Camidge, DR; Cao, D; Doebele, RC; Eakle, J; Goldschmidt, J; Reck, M; Spigel, D; Tehfe, M; Thomas, S; Verma, S; Yurasov, S, 2015)		0.42
"The primary endpoint of significant prolongation of PFS was not met; however, ramucirumab showed evidence of clinical activity in combination with pemetrexed and platinum in nonsquamous NSCLC patients."( Phase 2, randomized, open-label study of ramucirumab in combination with first-line pemetrexed and platinum chemotherapy in patients with nonsquamous, advanced/metastatic non-small cell lung cancer.
Alexandris, E; Bonomi, P; Bustin, F; Camidge, DR; Cao, D; Doebele, RC; Eakle, J; Goldschmidt, J; Reck, M; Spigel, D; Tehfe, M; Thomas, S; Verma, S; Yurasov, S, 2015)		0.42
"The aim of the study was to evaluate the efficacy and safety of intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy as induction therapy in clinical stage III unresectable non-small cell lung cancer (NSCLC)."( Intratumoral chemotherapy with paclitaxel liposome combined with systemic chemotherapy: a new method of neoadjuvant chemotherapy for stage III unresectable non-small cell lung cancer.
Ai, Z; Lu, B; Sun, L; Xu, J; Yan, X, 2015)		0.42
"To evaluate the efficacy and safety of lobaplatin combined with docetaxel in the treatment of the recurrent ovarian carcinoma."( [Clinical study on chemotherapy of lobaplatin combined with docetaxel in patients with relapsed ovarian cancer].
Li, X; Li, Y, 2014)		0.4
"The chemotherapy of lobaplatin combined with docetaxel is effective on recurrent and refractory ovarian cancer with low side effects, which has advantages over the second-line chemotherapy protocols."( [Clinical study on chemotherapy of lobaplatin combined with docetaxel in patients with relapsed ovarian cancer].
Li, X; Li, Y, 2014)		0.4
" The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer."( Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial.
Barrett, JC; Benzaquen, AO; Cibula, D; Colombo, N; Dougherty, B; Friedlander, M; Hirte, H; Lowe, ES; Mackay, H; Mahner, S; Mathijssen, RH; Oza, AM; Plante, M; Poole, C; Rowbottom, J; Schmalfeldt, B; Sonke, GS; Špaček, J; Vuylsteke, P, 2015)		0.42
" In this study, we evaluated the cytotoxic effect of curcumin alone and in combination with individual drugs like carboplatin, etoposide, or vincristine in a human retinoblastoma (RB) cancer cell line."( Synergistic Effect of Curcumin in Combination with Anticancer Agents in Human Retinoblastoma Cancer Cell Lines.
Krishnakumar, S; Sreenivasan, S, 2015)		0.42
"A drug-drug interaction was analyzed using the median effect/isobologram method and combination index values were used to characterize the interaction as synergistic or additive."( Synergistic Effect of Curcumin in Combination with Anticancer Agents in Human Retinoblastoma Cancer Cell Lines.
Krishnakumar, S; Sreenivasan, S, 2015)		0.42
" This analysis evaluated the safety and efficacy of nab-paclitaxel (nab-P) versus solvent-based paclitaxel (sb-P), both in combination with carboplatin (C), in patients with advanced non-small-cell lung cancer (NSCLC) and renal impairment."( Weekly nab-paclitaxel in combination with carboplatin as first-line therapy in patients with advanced non-small-cell lung cancer: analysis of safety and efficacy in patients with renal impairment.
Hirsh, V; Ko, A; Langer, CJ; Renschler, MF; Socinski, MA, 2015)		0.42
" Weekly paclitaxel combined with carboplatin appears to be a useful regimen with minimal toxicity for advanced thymic cancer."( [A case of thymic cancer effectively treated by weekly paclitaxel combined with carboplatin].
Asakawa, K; Hayashi, Y; Ishikawa, D; Kagamu, H; Kondo, R; Miura, S; Narita, I; Ohshima, Y; Okajima, M; Sakagami, T; Tanaka, J; Tanaka, T; Watanabe, S; Yoshizawa, H, 2014)		0.4
"Reported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response."( Randomized phase III trial of piroxicam in combination with mitoxantrone or carboplatin for first-line treatment of urogenital tract transitional cell carcinoma in dogs.
Allstadt, SD; Boostrom, B; Rebhun, RB; Rodriguez, CO; Skorupski, KA, 2015)		0.42
"This study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam."( Randomized phase III trial of piroxicam in combination with mitoxantrone or carboplatin for first-line treatment of urogenital tract transitional cell carcinoma in dogs.
Allstadt, SD; Boostrom, B; Rebhun, RB; Rodriguez, CO; Skorupski, KA, 2015)		0.42
" We sought to determine the relative value of BEV in combination with CBDCA versus CBDCA alone in patients with recurrent GBM."( The added value of bevacizumab concomitantly administered with carboplatin versus carboplatin alone in patients with recurrent glioblastomas.
Brace, G; Cakani, B; Diamandi, P; Kaloshi, G; Petrela, M; Rroji, A, )		0.13
"Eligible patients with progressive GBM following surgery, radiotherapy and temozolomide received CBDCA either alone (group 1, n = 25) or in combination with BEV (group 2, n = 23) at 5 mg/kg once every 3 weeks between June 2010 and December 2013."( The added value of bevacizumab concomitantly administered with carboplatin versus carboplatin alone in patients with recurrent glioblastomas.
Brace, G; Cakani, B; Diamandi, P; Kaloshi, G; Petrela, M; Rroji, A, )		0.13
" Our study demonstrated that the synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-κB via inhibition of the Akt/IKKα pathway and enhanced ERK1/2 activity."( Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin.
Ha, JH; Kang, HH; Kang, HS; Kang, JH; Kim, IK; Lee, HY; Lee, SH; Moon, HS; Yeo, CD, 2015)		0.42
"0 plus paclitaxel 200 mg/m(2) intravenously on day 1 every 3 weeks combined with either intravenous cetuximab weekly (arm A), intravenous cixutumumab every 2 weeks (arm B), or both (arm C)."( Three-arm, randomized, phase 2 study of carboplatin and paclitaxel in combination with cetuximab, cixutumumab, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: An Eastern Cooperative Oncology
Aggarwal, C; Dahlberg, SE; Hanna, NH; Hirsch, FR; Kolesar, JM; Ramalingam, SS; Schiller, JH, 2015)		0.42
"On the basis of the apparent lack of efficacy and excessive premature deaths, the current results do not support the continued investigation of carboplatin, paclitaxel, and cixutumumab either alone or in combination with cetuximab for patients with advanced NSCLC."( Three-arm, randomized, phase 2 study of carboplatin and paclitaxel in combination with cetuximab, cixutumumab, or both for advanced non-small cell lung cancer (NSCLC) patients who will not receive bevacizumab-based therapy: An Eastern Cooperative Oncology
Aggarwal, C; Dahlberg, SE; Hanna, NH; Hirsch, FR; Kolesar, JM; Ramalingam, SS; Schiller, JH, 2015)		0.42
" The objectives of the present study were to define maximum tolerated dose and the recommended phase II dose (RPTD) of AXL1717 in combination with gemcitabine HCl and carboplatin in non-small cell lung cancer (NSCLC)."( A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer.
Bergqvist, M; Bergström, S; Brandén, E; Ekman, S; Harmenberg, J; Holgersson, G; Jerling, M; Klockare, M; Koyi, H; Larsson, O; Lundström, KL; Ringbom, M, 2015)		0.42
" This study was undertaken to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of weekly nab-paclitaxel given in combination with carboplatin and concurrent radiotherapy in patients with unresectable stage III NSCLC."( nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent Radiotherapy in Stage III Non-Small Cell Lung Cancer.
Horn, L; Keedy, V; Lammers, PE; Lu, B; Shyr, Y, 2015)		0.42
"Escalating doses of once-weekly nab-paclitaxel were given along with once-weekly carboplatin area under the plasma concentration time curve (AUC) of 2 and concurrent radiotherapy 66 Gy in 33 fractions, followed by 2 cycles of carboplatin and nab-paclitaxel consolidation chemotherapy."( nab-Paclitaxel in Combination With Weekly Carboplatin With Concurrent Radiotherapy in Stage III Non-Small Cell Lung Cancer.
Horn, L; Keedy, V; Lammers, PE; Lu, B; Shyr, Y, 2015)		0.42
"This dose-escalating, phase I study was designed to identify the recommended dose of ipilimumab (3 or 10 mg/kg) by evaluating dose-limiting toxicity (DLT; Cycles 3 and 4) in phased combination with PTX (175 mg/m(2)) and CBDCA (area under the curve = 6) in Japanese patients with advanced NSCLC."( Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer.
Fujiwara, Y; Horinouchi, H; Kanda, S; Kitazono, S; Kubota, K; Mizugaki, H; Nokihara, H; Sekine, I; Tamura, T; Tokudome, T; Wakui, H; Yagishita, S; Yamamoto, N, 2015)		0.42
"Fifteen patients were enrolled and 12 received ipilimumab (n = 6, 3 mg/kg; n = 6, 10 mg/kg) in combination with PTX and CBDCA."( Phase I study of ipilimumab in phased combination with paclitaxel and carboplatin in Japanese patients with non-small-cell lung cancer.
Fujiwara, Y; Horinouchi, H; Kanda, S; Kitazono, S; Kubota, K; Mizugaki, H; Nokihara, H; Sekine, I; Tamura, T; Tokudome, T; Wakui, H; Yagishita, S; Yamamoto, N, 2015)		0.42
" We tested an inhibitor of the epidermal growth factor receptor, panitumumab in combination with chemotherapy."( A phase II clinical trial of weekly paclitaxel and carboplatin in combination with panitumumab in metastatic triple negative breast cancer.
Akman, S; Cole, J; Cowherd, S; Isom, S; Lawrence, JA; Melin, SA; Miller, LD; Pullikuth, A, 2015)		0.42
"The aim of the present study was to evaluate the efficacy and toxicity of palonosetron (PAL) and dexamethasone (DEX) on day 1 only in patients with gynecologic cancer receiving paclitaxel combined with carboplatin (TC)."( Palonosetron in combination with 1-day versus 3-day dexamethasone to prevent nausea and vomiting in patients receiving paclitaxel and carboplatin.
Furukawa, N; Ito, F; Kanayama, S; Tanase, Y, 2015)		0.42
"We conducted a phase I dose escalation study to evaluate the feasibility, maximum tolerated dose (MTD), and recommended dose (RD) of weekly irinotecan combined with fixed-dose carboplatin for patients with untreated small-cell lung cancer (SCLC)."( Weekly irinotecan combined with carboplatin for patients with small-cell lung cancer: A phase I study.
Inoue, A; Ishimoto, O; Maemondo, M; Nukiwa, T; Sugawara, S, 2015)		0.42
"The average time taken to reach a threefold relative tumour size was significantly longer after treatment with carboplatin combined with mild HT and HBO than after treatment with carboplatin and mild HT."( Efficacy of hyperbaric oxygen therapy combined with mild hyperthermia for improving the anti-tumour effects of carboplatin.
Imada, H; Korogi, Y; Kunugita, N; Ohguri, T; Okazaki, R; Ootsuyama, A; Shinya, N; Takashi, C; Uemura, H; Yahara, K; Youjirou, G, 2015)		0.42
"Patients had first participated in a phase I study of olaparib combined with carboplatin and/or paclitaxel."( Long-term safety and anti-tumour activity of olaparib monotherapy after combination with carboplatin and paclitaxel in patients with advanced breast, ovarian or fallopian tube cancer.
Beijnen, JH; Harms, E; Marchetti, S; Mergui-Roelvink, MW; Rehorst, H; Schellens, JH; Sonke, GS; Steeghs, N; van der Noll, R, 2015)		0.42
" Eligible patients were women with uterine cervical, endometrial or ovarian cancer scheduled to receive conventional TC regimen or dose-dense TC regimen; 116 patients were randomly assigned to receive palonosetron in combination with 1-day DEX or 3-day DEX."( Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following paclitaxel and carboplatin in patients with gynecologic cancers: A randomized, multicenter, phase-II trial.
Hayakawa, O; Iwasaki, M; Matsuura, M; Mizunuma, M; Nishikawa, A; Saito, T; Satohisa, S; Tanaka, R; Tanaka, S; Teramoto, M, 2015)		0.42
" We conducted a systematic review of the efficacy of bevacizumab in combination with taxane or non-taxane containing regimens for untreated, nonsquamous non-small-cell lung cancer patients."( Bevacizumab in Combination with Taxane versus Non-Taxane Containing Regimens for Advanced/Metastatic Nonsquamous Non-Small-Cell Lung Cancer: A Systematic Review.
Behera, M; Belani, CP; Chen, Z; Khuri, FR; Kim, S; Owonikoko, TK; Pillai, RN; Ramalingam, SS; Saba, NF; Steuer, C, 2015)		0.42
" Phase 2 and randomized trials reporting on the efficacy of bevacizumab combined with taxane or non-taxane regimens were selected."( Bevacizumab in Combination with Taxane versus Non-Taxane Containing Regimens for Advanced/Metastatic Nonsquamous Non-Small-Cell Lung Cancer: A Systematic Review.
Behera, M; Belani, CP; Chen, Z; Khuri, FR; Kim, S; Owonikoko, TK; Pillai, RN; Ramalingam, SS; Saba, NF; Steuer, C, 2015)		0.42
"The outcomes between taxane and non-taxane regimens when given in combination with bevacizumab for patients with nonsquamous non-small-cell lung cancer are comparable."( Bevacizumab in Combination with Taxane versus Non-Taxane Containing Regimens for Advanced/Metastatic Nonsquamous Non-Small-Cell Lung Cancer: A Systematic Review.
Behera, M; Belani, CP; Chen, Z; Khuri, FR; Kim, S; Owonikoko, TK; Pillai, RN; Ramalingam, SS; Saba, NF; Steuer, C, 2015)		0.42
" By using controlled method, 60 radical resected NSCLC patients undergoing NP/NC program in 2012 (vinorelbine 25 mg/m2, combined with cisplatin 75 mg/m2 on day 1 and day 8/on day 1 or on day 1, 2, and 3; or carboplatin AUC = 5 on day 1) were assigned to the control group (29 cases) and the test group (31 cases)."( [Treatment of Radical Resected NSCLC by Chinese Medicine Combined with Adjuvant Chemother- apy: a Clinical Study].
Chen, ZW; Hou, WX; Li, HG; Tian, JH; Xu, WJ; Yao, YL; Zhao, LH; Zhou, L; Zhu, LH, 2015)		0.42
"This study aimed to evaluate the efficacy and safety of nab-paclitaxel combined with carboplatin in Chinese patients with melanoma."( Efficacy and safety of nab-paclitaxel combined with carboplatin in Chinese patients with melanoma.
Ding, Y; Guo, YQ; Li, DD; Li, JJ; Peng, RQ; Wen, XZ; Zhang, X; Zhang, XS, 2015)		0.42
" The aim of this study was to assess the efficacy and safety of ifosfamide in combination with carboplatin and etoposide (ICE) in previously untreated patients with SCLC."( Efficacy and safety of ifosfamide in combination with carboplatin and etoposide in small cell lung cancer.
Koo, DH; Lee, HS; Lee, SS; Lee, YG; Lim, SY; Nam, H; Oh, S; Song, JU, 2015)		0.42
"The aim of this study was to evaluate the results with novel drug combination consisting of paclitaxel and carboplatin (PC) for salvage of refractory high-risk gestational trophoblastic neoplasia (GTN) previously treated with EMA-CO (etoposide, methotrexate, actinomycin, cyclophosphamide, and vincristine) and EMA-EP (etoposide, methotrexate, actinomycin, and cisplatin) regimens."( Refractory Gestational Trophoblastic Neoplasia: A Novel Drug Combination With Paclitaxel and Carboplatin Produces Durable Complete Remission.
Bafna, UD; Devi, UK; Kundargi, R; Pallavi, VR; Rathod, PS; Vijay, CR, 2015)		0.42
"LY2090314 (LY) is a glycogen synthase kinase 3 inhibitor with preclinical efficacy in xenograft models when combined with platinum regimens."( A first-in-human phase I dose-escalation, pharmacokinetic, and pharmacodynamic evaluation of intravenous LY2090314, a glycogen synthase kinase 3 inhibitor, administered in combination with pemetrexed and carboplatin.
Brail, LH; Burris, HA; Chow, KH; Cooksey, JF; Farrington, DL; Gray, JE; Infante, JR; Jackson, KA; Jones, SF; Simon, GR; Yeo, A; Zamek-Gliszczynski, MJ, 2015)		0.42
"The primary objective of this retrospective analysis is to assess efficacy and toxicity of a chemotherapeutic regimen using weekly carboplatin in combination with weekly paclitaxel as first-line therapy for advanced/metastatic non-small cell lung cancer (NSCLC)."( Weekly carboplatin in combination with weekly paclitaxel in the treatment of metastatic non-small cell lung cancer: a single center 10-year experience.
Brossart, P; Cathomas, R; Klingbiel, D; Mark, M; Mey, U; Volk, V; von Moos, R, 2016)		0.43
"All patients with stage IIIB/IV NSCLC treated with weekly carboplatin AUC (area under the curve) 3 days 1, 8, 15, q4w in combination with weekly paclitaxel 75 mg/m(2) days 1, 8, 15, q4w as first-line therapy at the Kantonsspital Graubuenden between August 2004 and May 2014 were retrospectively analyzed by medical record review."( Weekly carboplatin in combination with weekly paclitaxel in the treatment of metastatic non-small cell lung cancer: a single center 10-year experience.
Brossart, P; Cathomas, R; Klingbiel, D; Mark, M; Mey, U; Volk, V; von Moos, R, 2016)		0.43
"Weekly carboplatin in combination with weekly paclitaxel results in good response rates and acceptable toxicity in patients with advanced and metastatic NSCLC including patients with poor risk features (brain metastases, older age, and impaired PS)."( Weekly carboplatin in combination with weekly paclitaxel in the treatment of metastatic non-small cell lung cancer: a single center 10-year experience.
Brossart, P; Cathomas, R; Klingbiel, D; Mark, M; Mey, U; Volk, V; von Moos, R, 2016)		0.43
" Our patient was a 72-year-old man with stage IV SCLC combined with squamous cell carcinoma and interstitial lung disease (ILD)."( Nanoparticle Albumin-bound Paclitaxel+Carboplatin Therapy for Small Cell Lung Cancer Combined with Squamous Cell Carcinoma and Interstitial Lung Disease.
Azuma, Y; Hirashima, T; Kawase, I; Morishita, N; Okamoto, N; Osa, A; Shiroyama, T; Suzuki, H; Takeoka, S; Tamiya, M, 2015)		0.42
"To investigate the effect of poly(ADP-ribose)polymerase(PARP)inhibitor ABT888 combined with carbo on apoptosis of human breast cancer cells."( [Effect of poly(ADP-ribose)polymerase inhibitor combined with carbo on apoptosis of human breast cancer cells].
Ma, QC; Tao, QW; Xia, XY; Yang, B, 2015)		0.42
"We investigated the feasibility of cisplatin or carboplatin combined with pemetrexed as adjuvant treatment in patients with completely resected Stage IB/II Non-Small-Cell Lung Cancer (NSCLC)."( A randomized Phase 2 study of pemetrexed in combination with cisplatin or carboplatin as adjuvant chemotherapy in patients with completely resected stage IB or II Non-Small-Cell Lung Cancer.
Chouaid, C; Engel-Riedel, W; Fischer, JR; Mazières, J; Nguyen, T; Reck, M; Ripoche, V; Schmid-Bindert, G; Schuette, W; Soldatenkova, V; Stöhlmacher, J; Vinolas, N; Visseren-Grul, C; Wolf, M, 2015)		0.42
" It has been shown that compound kushen injection in combination with chemotherapy can enhance the efficacy and reduce the toxicity."( A multicenter randomized controlled open-label trial to assess the efficacy of compound kushen injection in combination with single-agent chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer: study protocol for a randomiz
Hou, W; Lin, HS; Liu, J; Wang, XQ, 2016)		0.43
" Three hundred seventy elderly patients with advanced non-small cell lung cancer will be randomly divided into experimental (n = 185) and control groups (n = 185) to receive compound kushen injection in combination with single-agent chemotherapy or standard platinum-based doublet chemotherapy for two cycles."( A multicenter randomized controlled open-label trial to assess the efficacy of compound kushen injection in combination with single-agent chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer: study protocol for a randomiz
Hou, W; Lin, HS; Liu, J; Wang, XQ, 2016)		0.43
" This study will determine whether or not the efficacy of compound kushen injection in combination with single-agent chemotherapy is comparable to that of platinum-based doublet chemotherapy, and whether or not the toxicity of compound kushen injection in combination with single-agent chemotherapy is lower than that of platinum-based doublet chemotherapy."( A multicenter randomized controlled open-label trial to assess the efficacy of compound kushen injection in combination with single-agent chemotherapy in treatment of elderly patients with advanced non-small cell lung cancer: study protocol for a randomiz
Hou, W; Lin, HS; Liu, J; Wang, XQ, 2016)		0.43
"This phase I trial aimed to assess the safety and determine the recommended Phase II dose (RP2D) of Cidofovir combined with chemoradiotherapy in patients with stage IB2-IVA cervical cancer."( Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients.
Adam, J; Bayar, MA; Chargari, C; Deutsch, E; Haie-Meder, C; Lanoy, E; Laporte, M; Levy, A; Magné, N; Mazeron, R; Mondini, M; Pautier, P; Soria, JC; Varga, A; Vassal, G, 2016)		0.43
"Cidofovir at a dose of 5mg/kg combined with chemoradiotherapy appeared tolerable and yielded tumor regressions."( Phase I trial evaluating the antiviral agent Cidofovir in combination with chemoradiation in cervical cancer patients.
Adam, J; Bayar, MA; Chargari, C; Deutsch, E; Haie-Meder, C; Lanoy, E; Laporte, M; Levy, A; Magné, N; Mazeron, R; Mondini, M; Pautier, P; Soria, JC; Varga, A; Vassal, G, 2016)		0.43
" This study assessed the efficacy of endostatin combined with concurrent chemoradiotherapy of non-small cell lung cancer (NSCLC)."( A phase II study of Endostatin in combination with paclitaxel, carboplatin, and radiotherapy in patients with unresectable locally advanced non-small cell lung cancer.
Deng, QH; Ji, YL; Jiang, H; Ma, SL; Sun, XJ; Xu, YP; Yu, XM; Zheng, YD, 2016)		0.43
" The real impact of endostatin as the first-line treatment combined with chemoradiotherapy on the survival of NSCLC patients remains to be determined."( A phase II study of Endostatin in combination with paclitaxel, carboplatin, and radiotherapy in patients with unresectable locally advanced non-small cell lung cancer.
Deng, QH; Ji, YL; Jiang, H; Ma, SL; Sun, XJ; Xu, YP; Yu, XM; Zheng, YD, 2016)		0.43
"Our aim was to evaluate the safety and efficacy of ipilimumab combined with standard first-line chemotherapy for patients with extensive-stage SCLC."( Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide as First-Line Therapy for Extensive-Stage SCLC.
Arriola, E; Cave, J; Cross, N; Danson, S; Galea, I; Geldart, T; Griffiths, R; Hamid, D; Maishman, T; Mulatero, C; Nolan, L; Ottensmeier, C; Potter, V; Stanton, L; Wheater, M; Woll, PJ, 2016)		0.43
"Ipilimumab in combination with carboplatin and etoposide might benefit a subgroup of patients with advanced SCLC."( Outcome and Biomarker Analysis from a Multicenter Phase 2 Study of Ipilimumab in Combination with Carboplatin and Etoposide as First-Line Therapy for Extensive-Stage SCLC.
Arriola, E; Cave, J; Cross, N; Danson, S; Galea, I; Geldart, T; Griffiths, R; Hamid, D; Maishman, T; Mulatero, C; Nolan, L; Ottensmeier, C; Potter, V; Stanton, L; Wheater, M; Woll, PJ, 2016)		0.43
" CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC."( Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.
Antonia, S; Borghaei, H; Brahmer, JR; Chen, AC; Chow, LQ; Gerber, DE; Gettinger, S; Goldman, JW; Harbison, CT; Hellmann, MD; Juergens, RA; Laurie, SA; Nathan, FE; Rizvi, NA; Shen, Y; Shepherd, FA, 2016)		0.43
"The aim of the present study was to investigate the efficacy of carboplatin plus paclitaxel (CP) combined with endostar against A375 melanoma cells in vitro and in vivo."( Impact of carboplatin plus paclitaxel combined with endostar against A375 melanoma cells: An in vitro and in vivo analysis.
Jia, DD; Jin, G; Li, T; Wu, H; Xia, LM; Zheng, AW, 2016)		0.43
" This single-center phase Ib study investigated the tolerability, safety, and pharmacokinetics of nivolumab combined with standard chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC)."( Safety and efficacy of nivolumab and standard chemotherapy drug combination in patients with advanced non-small-cell lung cancer: a four arms phase Ib study.
Fujiwara, Y; Goto, K; Horinouchi, H; Hozumi, H; Kanda, S; Kitazono, S; Kubo, E; Mizugaki, H; Nokihara, H; Shiraishi, H; Sunami, K; Tamura, T; Tanaka, A; Utsumi, H; Yamamoto, N, 2016)		0.43
"Patients with untreated stage IIIB/IV non-squamous NSCLC, stratified by MET diagnostic status, were randomized to receive onartuzumab (15 mg/kg intravenously every 3 weeks) or placebo in combination with either paclitaxel/platinum/bevacizumab (bevacizumab cohort), or in combination with platinum/pemetrexed (pemetrexed cohort) with maintenance bevacizumab or pemetrexed and onartuzumab/placebo as appropriate."( Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non-Small-Cell Lung Cancer.
Boyer, M; Braiteh, F; Cosgriff, T; De Braud, F; Hsu, J; Kaen, D; Kingsley, CD; Lawler, W; Lena, H; Lowe, T; Mekhail, T; Novello, S; Phan, S; Schütte, W; Wakelee, H; Zvirbule, Z, 2017)		0.46
"Onartuzumab does not appear to provide any additional clinical benefit when given in combination with current first-line standard-of-care chemotherapy for non-squamous NSCLC."( Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non-Small-Cell Lung Cancer.
Boyer, M; Braiteh, F; Cosgriff, T; De Braud, F; Hsu, J; Kaen, D; Kingsley, CD; Lawler, W; Lena, H; Lowe, T; Mekhail, T; Novello, S; Phan, S; Schütte, W; Wakelee, H; Zvirbule, Z, 2017)		0.46
"This phase I study aimed to determine the maximum tolerated dose (MTD) of Genexol-PM, when combined with carboplatin, as a first-line treatment in patients with advanced ovarian cancer."( An open-label, multicenter, phase I trial of a cremophor-free, polymeric micelle formulation of paclitaxel combined with carboplatin as a first-line treatment for advanced ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG-3016).
Kang, SB; Kim, YM; Kim, YT; Lee, SW, 2017)		0.46
"Genexol-PM combined with carboplatin was well tolerated as a first-line treatment, and good responses were observed in patients with advanced ovarian cancer."( An open-label, multicenter, phase I trial of a cremophor-free, polymeric micelle formulation of paclitaxel combined with carboplatin as a first-line treatment for advanced ovarian cancer: a Korean Gynecologic Oncology Group study (KGOG-3016).
Kang, SB; Kim, YM; Kim, YT; Lee, SW, 2017)		0.46
"This study evaluated safety, pharmacokinetics, and clinical activity of intravenous and oral rucaparib, a poly(ADP-ribose) polymerase inhibitor, combined with chemotherapy in patients with advanced solid tumours."( A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours.
Dieras, V; Evans, TJ; Giordano, H; Goble, S; Jaw-Tsai, S; Middleton, MR; Molife, LR; Plummer, R; Roxburgh, P; Spicer, J; Wilson, RH, 2017)		0.46
"Initially, patients received escalating doses of intravenous rucaparib combined with carboplatin, carboplatin/paclitaxel, cisplatin/pemetrexed, or epirubicin/cyclophosphamide."( A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours.
Dieras, V; Evans, TJ; Giordano, H; Goble, S; Jaw-Tsai, S; Middleton, MR; Molife, LR; Plummer, R; Roxburgh, P; Spicer, J; Wilson, RH, 2017)		0.46
"Oral rucaparib can be safely combined with a clinically relevant dose of carboplatin in patients with advanced solid tumours (Trial registration ID: NCT01009190)."( A phase I study of intravenous and oral rucaparib in combination with chemotherapy in patients with advanced solid tumours.
Dieras, V; Evans, TJ; Giordano, H; Goble, S; Jaw-Tsai, S; Middleton, MR; Molife, LR; Plummer, R; Roxburgh, P; Spicer, J; Wilson, RH, 2017)		0.46
"In this study, we aimed to evaluate the feasibility and efficacy of peptide-pulsed dendritic cell (DC) vaccine in combination with carboplatin and paclitaxel chemotherapy (DCCP) for patients with stage IV melanoma previously treated with dacarbazine-containing regimen."( Peptide-pulsed dendritic cell vaccine in combination with carboplatin and paclitaxel chemotherapy for stage IV melanoma.
Amagai, M; Fujita, T; Fukuda, K; Funakoshi, T; Kawakami, Y; Mori, M; Nakamura, Y; Okamoto, M; Sakurai, T; Taguchi, J; Tanese, K; Tanikawa, A, 2017)		0.46
" This phase I dose-escalation study evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics of pilaralisib in capsule and tablet formulations, administered in combination with paclitaxel and carboplatin in patients with advanced solid tumors."( Phase I Dose-Escalation Study of Pilaralisib (SAR245408, XL147) in Combination with Paclitaxel and Carboplatin in Patients with Solid Tumors.
Castell, C; Jiang, J; Lager, J; Liu, L; Mutch, D; Traynor, AM; Wheler, J, 2017)		0.46
" The MTD of pilaralisib tablets in combination with paclitaxel and carboplatin was determined to be 200 mg QD."( Phase I Dose-Escalation Study of Pilaralisib (SAR245408, XL147) in Combination with Paclitaxel and Carboplatin in Patients with Solid Tumors.
Castell, C; Jiang, J; Lager, J; Liu, L; Mutch, D; Traynor, AM; Wheler, J, 2017)		0.46
" Despite a clear potential in inhibiting these proteins in ovarian cancer, as a single agent or in combination with a carboplatin treatment, we need to target kinases in tandem because of their capacity to trigger compensatory pathways that synergize to promote drug resistance."( Dasatinib + Gefitinib, a non platinum-based combination with enhanced growth inhibitory, anti-migratory and anti-invasive potency against human ovarian cancer cells.
Jean-Claude, B; Thibault, B, 2017)		0.46
"Here we target EGFR, c-Src and Met individually or in combination with carboplatin, using Gefitinib, Dasatinib and Crizotinib respectively, in a panel of carboplatin-sensitive (OVCAR-3, IGROV-1 and A2780) and carboplatin-resistant cells (SKOV-3 and EFO-21)."( Dasatinib + Gefitinib, a non platinum-based combination with enhanced growth inhibitory, anti-migratory and anti-invasive potency against human ovarian cancer cells.
Jean-Claude, B; Thibault, B, 2017)		0.46
"Crizotinib, Dasatinib and Gefitinib, alone or in combination with carboplatin, showed a cell-specific cytotoxic synergy in ovarian cancer cells."( Dasatinib + Gefitinib, a non platinum-based combination with enhanced growth inhibitory, anti-migratory and anti-invasive potency against human ovarian cancer cells.
Jean-Claude, B; Thibault, B, 2017)		0.46
" This phase I trial was conducted to determine the safety profile, maximal tolerated dose, and recommended phase II dose and schedule of oral ridaforolimus combined with paclitaxel and carboplatin in patients with solid tumor cancers."( Phase I study of oral ridaforolimus in combination with paclitaxel and carboplatin in patients with solid tumor cancers.
Apte, SM; Chon, HS; Kang, S; Lee, JK; Shahzad, MM; Wenham, RM; Williams-Elson, I, 2017)		0.46
"In this randomized, double-blind, placebo-controlled phase 1b/2 study we assessed the efficacy/safety of rilotumumab or ganitumab combined with etoposide and carboplatin or cisplatin as first-line treatment in patients with extensive stage small-cell lung cancer (ES-SCLC)."( A Randomized, Placebo-Controlled, Phase 1b/2 Study of Rilotumumab or Ganitumab in Combination With Platinum-Based Chemotherapy as First-Line Treatment for Extensive-Stage Small-Cell Lung Cancer.
Besse, B; Dols, MC; Dubey, S; Glisson, B; Jain, R; Jiang, Y; Menon, H; Nackaerts, K; Orlov, S; Paz-Ares, L; Ramlau, R; Schupp, M; Tang, R; Zhang, Y; Zhu, M, 2017)		0.46
"This phase-I/phase-II study evaluated panobinostat in combination with ifosfamide, carboplatin, etoposide (P-ICE) in relapsed/refractory classical Hodgkin lymphoma."( Phase-I and randomized phase-II trial of panobinostat in combination with ICE (ifosfamide, carboplatin, etoposide) in relapsed or refractory classical Hodgkin lymphoma.
Claret, L; Copeland, AR; Fanale, MA; Fayad, LE; Feng, L; Fowler, N; Hagemeister, FB; Hu, B; Nastoupil, LJ; Neelapu, S; Nieto, Y; Oki, Y; Rodriguez, MA; Romaguera, J; Samaniego, F; Turturro, F; Westin, JR; Younes, A, 2018)		0.48
" Ongoing studies are evaluating ipilimumab in combination with nivolumab in this population."( Phase III Trial of Ipilimumab Combined With Paclitaxel and Carboplatin in Advanced Squamous Non-Small-Cell Lung Cancer.
Ahn, MJ; Barlesi, F; Fadeeva, N; Ganea, DE; Gonzalez Mella, PF; Govindan, R; Han, B; Jassem, J; Kopit, J; Kurata, T; Lee, KH; Li, M; O'Byrne, K; Postmus, PE; Reck, M; Schneider, CP; Szczesna, A; Tamura, T; Tschaika, M; Vladimirov, V; Von Pawel, J; Zhang, L, 2017)		0.46
" This study aimed to evaluate the pan-PI3K inhibitor pictilisib in combination with first-line treatment regimens that were the standard of care at the time of study, in patients with NSCLC."( A phase IB dose-escalation study of the safety and pharmacokinetics of pictilisib in combination with either paclitaxel and carboplatin (with or without bevacizumab) or pemetrexed and cisplatin (with or without bevacizumab) in patients with advanced non-s
Adjei, AA; Bahleda, R; Besse, B; Dy, GK; Ferte, C; Groen, HJM; Lin, W; Morrissey, K; Planchard, D; Schutzman, JL; Shankar, G; Soria, JC; Ware, J; Zhou, J, 2017)		0.46
" We conducted a single-center phase 1 study evaluating dose-escalated ibrutinib, in a 3-by-3 design, in combination with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in physiologically transplant-eligible rel/ref DLBCL patients."( A phase 1 study of ibrutinib in combination with R-ICE in patients with relapsed or primary refractory DLBCL.
Courtien, AI; Devlin, SM; Drullinsky, P; Gerecitano, J; Kumar, A; Matasar, MJ; McCall, SJ; Miller, ST; Moskowitz, CH; Noy, A; Palomba, ML; Portlock, CS; Sauter, CS; Schoder, H; Straus, DJ; Younes, A; Zelenetz, AD, 2018)		0.48
"Low-intensity ultrasound (LIUS) combined with chemotherapy is an innovative modality for cancer treatment, but its effect on orthotopic carcinoma remains unknown."( Effects of low-intensity ultrasound combined with low-dose carboplatin in an orthotopic hamster model of tongue cancer: A preclinical study.
Cao, W; Chen, H; Hu, Z; Ji, L; Li, HX; Liu, GY; Lv, YK; Yang, D; Zhang, FM; Zheng, JH, 2018)		0.48
"The lack of efficacy associated with anti-EGFL7 combined with standard bevacizumab and chemotherapy in this phase II trial in non-small cell lung carcinoma is consistent with the lack of benefit observed in colorectal carcinoma, highlighting the challenge of enhancing the efficacy of VEGF inhibition in unselected populations."( Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First-Line Nonsquamous Non-Small Cell Lung Cancer.
Anderson, M; Barlesi, F; Chang, I; Chen, D; Ervin, T; Hegde, P; Juhász, E; Losonczy, G; McCall, B; Reck, M; Rhee, I; Spigel, DR; von Pawel, J; Wakshull, E; Ye, W, 2018)		0.48
" This phase II trial evaluated the efficacy of the anti-EGFL7 antibody, parsatuzumab, in combination with bevacizumab plus platinum-based therapy for advanced or recurrent nonsquamous non-small cell lung cancer (NS-NSCLC)."( Randomized Phase II Trial of Parsatuzumab (Anti-EGFL7) or Placebo in Combination with Carboplatin, Paclitaxel, and Bevacizumab for First-Line Nonsquamous Non-Small Cell Lung Cancer.
Anderson, M; Barlesi, F; Chang, I; Chen, D; Ervin, T; Hegde, P; Juhász, E; Losonczy, G; McCall, B; Reck, M; Rhee, I; Spigel, DR; von Pawel, J; Wakshull, E; Ye, W, 2018)		0.48
"BTH1677, a beta-glucan pathogen-associated molecular pattern molecule, drives an anti-cancer immune response in combination with oncology antibody therapies."( A randomized, controlled trial evaluating the efficacy and safety of BTH1677 in combination with bevacizumab, carboplatin, and paclitaxel in first-line treatment of advanced non-small cell lung cancer.
Dupuis, M; Engel-Riedel, W; Gargano, M; Huhn, RD; Lowe, J; Mattson, P; Patchen, ML; Richard Trout, J; Schneller, F; Trinh, MM; Walsh, R, 2018)		0.48
" spOS-2 cells were incubated up to 72 h with propolis (50 μg/ml) alone or in combination with CARB (10-400 μmol/l), DOX (0."( Positive effects of antitumor drugs in combination with propolis on canine osteosarcoma cells (spOS-2) and mesenchymal stem cells.
Bernardino, PN; Bersano, PRO; Lima Neto, JF; Sforcin, JM, 2018)		0.48
"This was the first large-scale prospective observational Japanese study evaluating the safety and efficacy of bevacizumab combined with paclitaxel and carboplatin for newly diagnosed advanced ovarian cancer."( Bevacizumab combined with platinum-taxane chemotherapy as first-line treatment for advanced ovarian cancer: a prospective observational study of safety and efficacy in Japanese patients (JGOG3022 trial).
Arakawa, A; Asai-Sato, M; Hongo, A; Inokuchi, Y; Kamiura, S; Kato, K; Komiyama, S; Matsumoto, T; Sugiyama, T; Tabata, T; Takano, H; Takeshima, N, 2019)		0.51
"To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients."( Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer.
Birrer, MJ; Gonzalez-Martin, A; Malek, K; Martin, LP; Moore, KN; O'Malley, DM; Vergote, I, 2018)		0.48
"These data demonstrate that mirvetuximab soravtansine combined with carboplatin is a well-tolerated and highly active regimen in recurrent, platinum-sensitive ovarian cancer."( Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer.
Birrer, MJ; Gonzalez-Martin, A; Malek, K; Martin, LP; Moore, KN; O'Malley, DM; Vergote, I, 2018)		0.48
" The landmark Japanese Gynaecologic Oncology Group (JGOG) 3016 study demonstrated significant improvements in progression-free survival and overall survival with dose dense weekly administration of paclitaxel in combination with 3-weekly carboplatin."( Weekly versus 3-weekly paclitaxel in combination with carboplatin in advanced ovarian cancer: which is the optimal adjuvant chemotherapy regimen?
Lee, MX; Tan, DS, 2018)		0.48
" The drug combination was cytotoxic to TNBC cells, both with regards to short‑term and long‑term sensitivity, as determined using colony forming assays, and they exerted strong synergistic effects on MDA‑MB‑231 and CAL51 cell lines."( Antitumor effects and mechanisms of olaparib in combination with carboplatin and BKM120 on human triple‑negative breast cancer cells.
Hu, Y; Yang, Q; Zhang, J; Zhao, H, 2018)		0.48
"This study examined safety, pharmacokinetics, and efficacy of veliparib, a PARP inhibitor, combined with carboplatin and etoposide in patients with extensive-stage (ED) small cell lung cancer (SCLC) and other solid tumors."( A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors.
Atrafi, F; Byers, LA; Calles, A; Camidge, DR; Chae, YK; Gabrail, NY; Garralda, E; Groen, HJM; He, L; Hoening, E; Hu, B; Komarnitsky, P; Lolkema, MP; Nuthalapati, S; Sangha, RS; Tian, T; Viteri, S, 2019)		0.51
"Thirty-nine patients were enrolled to determine the recommended phase II dose of 240 mg veliparib for 14 days combined with carboplatin and etoposide based on long-term tolerability."( A Phase I Dose-Escalation Study of Veliparib Combined with Carboplatin and Etoposide in Patients with Extensive-Stage Small Cell Lung Cancer and Other Solid Tumors.
Atrafi, F; Byers, LA; Calles, A; Camidge, DR; Chae, YK; Gabrail, NY; Garralda, E; Groen, HJM; He, L; Hoening, E; Hu, B; Komarnitsky, P; Lolkema, MP; Nuthalapati, S; Sangha, RS; Tian, T; Viteri, S, 2019)		0.51
" However, which regimen, among cisplatin (TP), carboplatin (TC) or fluorouracil (TF) in combination with paclitaxel concurrent with radiotherapy, provides best prognosis with minimum adverse events is still unknown and very few studies focus on this field."( Comparison of paclitaxel in combination with cisplatin (TP), carboplatin (TC) or fluorouracil (TF) concurrent with radiotherapy for patients with local advanced oesophageal squamous cell carcinoma: a three-arm phase III randomized trial (ESO-Shanghai 2).
Ai, D; Badakhshi, H; Cao, J; Chen, Y; Deng, J; Fan, J; Fan, M; Huang, G; Li, J; Li, L; Li, Y; Lin, Q; Liu, Q; Luo, H; Ren, W; Wei, S; Wu, K; Yang, H; Ye, J; Zhang, J; Zhao, K; Zhao, W; Zheng, X; Zhou, J; Zhu, H; Zhu, Z, 2018)		0.48
" In a preclinical study TNBC cells were treated with the first-generation proteasome inhibitor bortezomib in combination with cisplatin and synergistic efficacy was demonstrated."( Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).
Balic, M; Bartsch, R; Burgstaller, S; Egle, D; Fuchs, D; Gampenrieder, SP; Greil, R; Melchardt, T; Mlineritsch, B; Petru, E; Petzer, A; Rinnerthaler, G; Rossmann, D; Rumpold, H; Singer, CF; Ulmer, H, 2018)		0.48
" Patients will receive ixazomib in combination with carboplatin on days 1, 8, and 15 in a 28-day cycle."( Ixazomib in combination with carboplatin in pretreated women with advanced triple-negative breast cancer, a phase I/II trial of the AGMT (AGMT MBC-10 trial).
Balic, M; Bartsch, R; Burgstaller, S; Egle, D; Fuchs, D; Gampenrieder, SP; Greil, R; Melchardt, T; Mlineritsch, B; Petru, E; Petzer, A; Rinnerthaler, G; Rossmann, D; Rumpold, H; Singer, CF; Ulmer, H, 2018)		0.48
"The second primary cancer (SPC) incidence after treatment with platinum-based chemotherapy and cetuximab in combination with radiotherapy has not been previously reported."( Incidence of second primary cancers after radiotherapy combined with platinum and/or cetuximab in head and neck cancer patients.
Aebersold, DM; Bojaxhiu, B; Elicin, O; Giger, R; Rauch, D; Sermaxhaj, B; Shelan, M, 2019)		0.51
"Recent randomized phase III trials (KEYNOTE-407 and IMpower131) reported that adding anti-programmed death (ligand) 1 (anti-PD-(L)1) antibodies in combination with taxane-platinum improve the therapeutic efficacy for advanced squamous non-small-cell lung cancer (NSCLC)."( Which is the optimal immunotherapy for advanced squamous non-small-cell lung cancer in combination with chemotherapy: anti-PD-1 or anti-PD-L1?
Zhang, L; Zhang, Y; Zhou, H, 2018)		0.48
"Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with extensive-disease SCLC, and the study was prematurely terminated."( Phase II Study of Roniciclib in Combination with Cisplatin/Etoposide or Carboplatin/Etoposide as First-Line Therapy in Patients with Extensive-Disease Small Cell Lung Cancer.
Albert, I; Barlesi, F; Bidoli, P; Cadranel, J; Chung, J; Drews, U; Fritsch, A; Govindan, R; Horn, L; Juhász, E; Kowalski, D; Novello, S; Reck, M; Robinet, G; Wagner, A, 2019)		0.51
"To provide real-life outcomes of carboplatin combined with oral or intravenous (IV) etoposide (Etop) in advanced EP-PD-NEC, from 2 specialist centres."( Carboplatin in Combination with Oral or Intravenous Etoposide for Extra-Pulmonary, Poorly-Differentiated Neuroendocrine Carcinomas.
Barriuso, J; Fazio, N; Frizziero, M; Hubner, RA; Kordatou, Z; Lamarca, A; Manoharan, P; Mansoor, W; McNamara, MG; Nuttall, C; Spada, F; Valle, JW, 2019)		0.51
"Findings of this study suggest that MSCT combined with other modalities targeting multiple pathways and cellular vulnerabilities may bring about remarkable improvements in survival outcomes and treatment response rates in metastatic NSCLC, without additional safety concerns."( Feasibility study of metabolically supported chemotherapy with weekly carboplatin/paclitaxel combined with ketogenic diet, hyperthermia and hyperbaric oxygen therapy in metastatic non-small cell lung cancer.
Iyikesici, MS, 2019)		0.51
"Atezolizumab (a monoclonal antibody against PD-L1), which restores anticancer immunity, improved overall survival in patients with previously treated non-small-cell lung cancer and also showed clinical benefit when combined with chemotherapy as first-line treatment of non-small-cell lung cancer."( Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 tria
Archer, V; Cappuzzo, F; Conter, HJ; Daniel, D; Hussein, M; Kopp, HG; Kowanetz, M; Lin, W; McCleod, M; McCune, S; Mekhail, T; Morabito, A; Ochi Lohmann, T; Reinmuth, N; Rittmeyer, A; Sadiq, A; Sandler, A; Wang, L; West, H; Zer, A, 2019)		0.51
" This study supports the benefit of atezolizumab, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer."( Atezolizumab in combination with carboplatin plus nab-paclitaxel chemotherapy compared with chemotherapy alone as first-line treatment for metastatic non-squamous non-small-cell lung cancer (IMpower130): a multicentre, randomised, open-label, phase 3 tria
Archer, V; Cappuzzo, F; Conter, HJ; Daniel, D; Hussein, M; Kopp, HG; Kowanetz, M; Lin, W; McCleod, M; McCune, S; Mekhail, T; Morabito, A; Ochi Lohmann, T; Reinmuth, N; Rittmeyer, A; Sadiq, A; Sandler, A; Wang, L; West, H; Zer, A, 2019)		0.51
" This phase Ib trial was designed to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RPh2) for IPA in combination with taxane and platinum therapy (C/P)."( A phase 1b dose escalation study of ipafricept (OMP54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer.
Brachmann, RK; Burger, RA; Farooki, A; Gunderson, CC; Kapoun, AM; Mantia-Smaldone, G; McMeekin, DS; Moore, KN; Morgan, MA; O'Cearbhaill, RE; Sabbatini, P; Stagg, R, 2019)		0.51
"IPA is well tolerated in combination with sequential C/P."( A phase 1b dose escalation study of ipafricept (OMP54F28) in combination with paclitaxel and carboplatin in patients with recurrent platinum-sensitive ovarian cancer.
Brachmann, RK; Burger, RA; Farooki, A; Gunderson, CC; Kapoun, AM; Mantia-Smaldone, G; McMeekin, DS; Moore, KN; Morgan, MA; O'Cearbhaill, RE; Sabbatini, P; Stagg, R, 2019)		0.51
"This phase 1b study investigated the maximum tolerated dose (MTD; primary objective), safety, pharmacokinetics, and antitumor activity (secondary objectives) of eribulin combined with carboplatin in patients with solid tumors and, in particular, non-small cell lung cancer (NSCLC)."( A phase 1b, multicenter, open-label, dose-finding study of eribulin in combination with carboplatin in advanced solid tumors and non-small cell lung cancer.
Aisner, J; Dittrich, C; Goel, S; Jain, M; Kumar, K; Petrylak, DP; Reyderman, L; Song, J; Swami, U, 2019)		0.51
" Our previous prospective pilot study demonstrated the safety and efficacy of weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer (NSCLC) with IIPs."( Weekly paclitaxel in combination with carboplatin for advanced non-small-cell lung cancer complicated by idiopathic interstitial pneumonias: a single-arm phase II study.
Atsumi, K; Azuma, A; Fukuizumi, A; Gemma, A; Hisakane, K; Kobayashi, K; Kubota, K; Minegishi, Y; Noro, R; Omori, M; Seike, M; Sugano, T; Takahashi, S; Takano, N; Takeuchi, S, 2019)		0.51
"To observe the clinical efficacy and safety of bevacizumab (BEV) combined with paclitaxel on recurrent ovarian cancer."( Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer.
Cong, J; Hou, J; Jiang, H; Liu, R; Wang, J; Wang, X, )		0.13
"The clinical therapeutic effect of BEV combined with paclitaxel in patients with recurrent ovarian cancer was improved, suggesting it might be beneficial for the treatment of ovarian cancer."( Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer.
Cong, J; Hou, J; Jiang, H; Liu, R; Wang, J; Wang, X, )		0.13
" We performed a single-arm multicentre pilot study of AF in combination with standard of care (SOC) (amputation + carboplatin)."( Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma.
Bennett, TC; Bird, G; Brockley, L; Cooper, M; Endo-Munoz, L; Lane, A; Matigian, N; O'Connell, K; Peaston, A; Saunders, NA; Sommerville, S; Straw, RC; Thamm, DH; Thomson, M; Topkas, E; Wu, SY, 2020)		0.56
" This Phase I trial (NCT00516724) evaluated the safety, pharmacokinetics (PK) and preliminary efficacy of olaparib combined with carboplatin and/or paclitaxel."( Phase I study of continuous olaparib capsule dosing in combination with carboplatin and/or paclitaxel (Part 1).
Ang, JE; Arkenau, HT; Beijnen, JH; Brunetto, AT; de Bono, JS; de Jonge, MJA; Jager, A; Lolkema, MP; Marchetti, S; Mergui-Roelvink, MWJ; Schellens, JHM; Tchakov, I; van der Biessen, DA; van der Noll, R, 2020)		0.56
" This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC."( A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.
Aghajanian, C; Armstrong, DK; Bell-McGuinn, KM; Chen, A; Duska, LR; Fracasso, PM; Gordon, S; Gray, HJ; Guntupalli, SR; Hagemann, AR; Mathews, CA; Miller, A; Moore, KN; O'Cearbhaill, RE; O'Malley, D; Schilder, RJ; Walker, JL, 2020)		0.56
"To study the treatment of advanced lung adenocarcinoma in the elderly with pemetrexed combined with platinum drugs."( Study on the treatment of advanced lung adenocarcinoma in the elderly with pemetrexed combined with platinum drugs.
Ba, X; Bian, L; Han, J; Zhao, G, 2019)		0.51
"Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy."( Efficacy and safety of 5 mg olanzapine combined with aprepitant, granisetron and dexamethasone to prevent carboplatin-induced nausea and vomiting in patients with gynecologic cancer: A multi-institution phase II study.
Abe, M; Arai, T; Fujita, Y; Hayasaki, Y; Iihara, H; Kado, N; Mori, M; Morishige, KI; Murase, S; Nakamura, K; Sakurai, M; Shimaoka, R; Shimokawa, M; Suzuki, A; Takenaka, M; Yamamoto, S, 2020)		0.56
" We present the results of a phase I study of an oral selective gamma secretase (GS) inhibitor (critical to Notch signaling), RO4929097 in combination with neoadjuvant chemotherapy for operable triple negative breast cancer."( A phase I study of an oral selective gamma secretase (GS) inhibitor RO4929097 in combination with neoadjuvant paclitaxel and carboplatin in triple negative breast cancer.
Badawi, M; Carson, W; Cherian, M; Grever, M; Kassem, M; Layman, R; Ling, Y; Lustberg, M; Morgan, E; Mrozek, E; Phelps, M; Ramaswamy, B; Reinbolt, R; Sardesai, S; Stephens, J; Stover, D; VanDeusen, J; Wei, L; Wesolowski, R; Williams, N, 2020)		0.56
" This study aimed to investigate VEGFA messenger RNA expression in patients with EGFR mutation, and to further compare the efficacy of bevacizumab combined with platinum-based chemotherapy between EGFR-mutant and wild-type patients."( Potential Benefits of Bevacizumab Combined With Platinum-Based Chemotherapy in Advanced Non-Small-Cell Lung Cancer Patients With EGFR Mutation.
Gen, S; Hase, T; Hasegawa, Y; Hashimoto, N; Kodama, Y; Matsui, A; Miyazawa, A; Morise, M; Sato, M; Tamiya, Y; Tanaka, I, 2020)		0.56
" Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple-negative (TNBC) or hormone receptor (HR)-positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA-repair pathway based on FA triple staining immunofluorescence assay."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020)		0.56
" This study demonstrates that a higher dose of veliparib is tolerable and active in combination with carboplatin alone."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020)		0.56
"To explore the efficacy and safety of intra-arterial chemotherapy (IAC) combined with vincristine + etoposide + carboplatin (VEC) intravenous chemotherapy (IVC) in the treatment of advanced retinoblastoma (RB)."( Intra-arterial chemotherapy combined with VEC intravenous chemotherapy in the treatment of advanced retinoblastoma.
Liu, J; Xu, K; Zhang, C, )		0.13
"A total of 86 child patients (98 eyes) newly diagnosed with advanced RB (stage D and E), among whom 42 cases (49 eyes) underwent IVC and IAC combined with local ocular treatment (IVC+IAC group), and 44 cases (49 eyes) were treated with IAC combined with local ocular treatment (IAC group)."( Intra-arterial chemotherapy combined with VEC intravenous chemotherapy in the treatment of advanced retinoblastoma.
Liu, J; Xu, K; Zhang, C, )		0.13
"Atezolizumab was the first immune checkpoint inhibitor (ICI) to be introduced as a first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), in combination with carboplatin and etoposide (CE) chemotherapy."( Atezolizumab in combination with carboplatin and etoposide for heavily treated small cell lung cancer.
Hirose, K; Kataoka, N; Kunimatsu, Y; Ogura, Y; Sato, I; Sugimoto, T; Tachibana, Y; Takeda, T; Tani, N, 2020)		0.56
") by means of convection-enhanced delivery (CED) or osmotic pumps, in combination with either synchrotron or conventional X-irradiation."( Radiation therapy combined with intracerebral convection-enhanced delivery of cisplatin or carboplatin for treatment of the F98 rat glioma.
Balosso, J; Barth, RF; Bobyk, L; Elleaume, H; Huo, T; Nakkula, R; Rousseau, J; Yang, W, 2020)		0.56
" To address potential concerns that iohexol administered during a course of chemotherapy impacts that therapy, we performed in vitro and in vivo pharmacokinetic drug-drug interaction evaluations of iohexol."( Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.
Beumer, JH; Christner, S; Chu, E; Guo, J; Holleran, JL; Ivy, SP; Joshi, A; Kiesel, B; Miller, BM; Parise, RA; Taylor, S; Venkataramanan, R, 2020)		0.56
"Iohexol is unlikely to affect the clinical pharmacokinetics of carboplatin, paclitaxel, gemcitabine, or other agents used in combination with carboplatin treatment."( Evaluation of the pharmacokinetic drug-drug interaction potential of iohexol, a renal filtration marker.
Beumer, JH; Christner, S; Chu, E; Guo, J; Holleran, JL; Ivy, SP; Joshi, A; Kiesel, B; Miller, BM; Parise, RA; Taylor, S; Venkataramanan, R, 2020)		0.56
" However, no study has reported on its prophylactic value against chemotherapy-associated acute IPF exacerbations when combined with chemotherapy for non-small cell lung cancer (NSCLC)."( Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study.
Akazawa, Y; Ishijima, M; Kanazu, M; Kuge, T; Mori, M; Okabe, F; Uenami, T; Yamaguchi, T; Yamamoto, Y; Yano, Y, 2020)		0.56
" Patients were treated with pirfenidone combined with carboplatin and nanoparticle albumin-bound paclitaxel or S-1 as first-line chemotherapy."( Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study.
Akazawa, Y; Ishijima, M; Kanazu, M; Kuge, T; Mori, M; Okabe, F; Uenami, T; Yamaguchi, T; Yamamoto, Y; Yano, Y, 2020)		0.56
"The present study found that pirfenidone combined with carboplatin-based regimens or ICIs might be safe first-line chemotherapy for patients with IPF and NSCLC."( Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study.
Akazawa, Y; Ishijima, M; Kanazu, M; Kuge, T; Mori, M; Okabe, F; Uenami, T; Yamaguchi, T; Yamamoto, Y; Yano, Y, 2020)		0.56
"SIGNIFICANT FINDINGS OF THE STUDY: No patients with IPF and NSCLC who received pirfenidone in combination with first-line carboplatin-based chemotherapy or late-line ICIs developed acute IPF exacerbations."( Safety and effectiveness of pirfenidone combined with carboplatin-based chemotherapy in patients with idiopathic pulmonary fibrosis and non-small cell lung cancer: A retrospective cohort study.
Akazawa, Y; Ishijima, M; Kanazu, M; Kuge, T; Mori, M; Okabe, F; Uenami, T; Yamaguchi, T; Yamamoto, Y; Yano, Y, 2020)		0.56
" Pyrotinib combined with capecitabine is widely used to treat HER2-positive metastatic breast cancer in patients who have been previously treated with anthracyclines, taxanes, and trastuzumab."( Durable clinical benefit from pyrotinib combined with carboplatin in HER2-positive relapsed breast cancer previously treated with taxanes, anthracyclines, and trastuzumab.
Cui, M; Wu, J; Zhang, L; Zhu, W, 2020)		0.56
" We performed a phase I study to determine the safety and maximum tolerated dose (MTD) of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory (R/R) T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL)."( Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma
Chan, JY; Farid, M; Lim, C; Lim, ST; Martin, P; Poon, E; Somasundaram, N; Tang, T; Tao, M; Toh, SQ; Yan, SX; Yunon, MJ, 2021)		0.62
"We studied 30 patients with OC treated with paclitaxel combined with carboplatin chemotherapy."( Changes in left ventricular function induced by carboplatin combined with paclitaxel in patients with ovarian cancer identified using three-dimensional spot tracking imaging technology.
Dong, S; Guo, X; Huang, L; Lu, G; Qin, W; Wang, Z; Zhai, Z; Zhang, C, 2021)		0.62
" In this randomized, open-label, phase II study, we characterized the efficacy and safety of bevacizumab in combination with carboplatin plus paclitaxel (CPB) in patients with previously untreated advanced MM."( Randomized Phase II Study of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Mucosal Melanoma.
Bai, X; Chi, Z; Cui, C; Dai, J; Guo, J; Kong, Y; Li, S; Lian, B; Mao, L; Sheng, X; Si, L; Tang, B; Wang, X; Yan, X; Yao, H; Zhou, L, 2021)		0.62
" In PRO-002, NUC-1031 was combined with carboplatin in recurrent ovarian cancer."( A Phase Ib Open-Label, Dose-Escalation Study of NUC-1031 in Combination with Carboplatin for Recurrent Ovarian Cancer.
Blagden, SP; Gabra, H; Ghazaly, E; Gnanaranjan, C; Harrison, DJ; Kazmi, F; McCracken, NW; Nicum, S; Roux, RL; Spiers, L; Sukumaran, A, 2021)		0.62
"NUC-1031 combined with carboplatin is well tolerated in recurrent ovarian cancer."( A Phase Ib Open-Label, Dose-Escalation Study of NUC-1031 in Combination with Carboplatin for Recurrent Ovarian Cancer.
Blagden, SP; Gabra, H; Ghazaly, E; Gnanaranjan, C; Harrison, DJ; Kazmi, F; McCracken, NW; Nicum, S; Roux, RL; Spiers, L; Sukumaran, A, 2021)		0.62
"This phase I study evaluated safety, tolerability, pharmacokinetics, and preliminary activity of the PI3K/mTORC1/2 dual inhibitor gedatolisib combined with carboplatin and paclitaxel."( Phase I Dose-Escalation Study of the Dual PI3K-mTORC1/2 Inhibitor Gedatolisib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors.
Brandt, S; Colombo, I; Frattini, M; Gaggetta, S; Genta, S; Guidi, M; Martorana, F; Moser, L; Pascale, M; Samartzis, EP; Sessa, C; Stathis, A; Terrot, T, 2021)		0.62
"Gedatolisib combined with carboplatin and paclitaxel is tolerable, and preliminary efficacy was observed especially in CCOC."( Phase I Dose-Escalation Study of the Dual PI3K-mTORC1/2 Inhibitor Gedatolisib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors.
Brandt, S; Colombo, I; Frattini, M; Gaggetta, S; Genta, S; Guidi, M; Martorana, F; Moser, L; Pascale, M; Samartzis, EP; Sessa, C; Stathis, A; Terrot, T, 2021)		0.62
"Between November 2013 and May 2015, 71 patients were randomized to chemotherapy in combination with DCVAC/OvCa or to chemotherapy alone."( Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial.
Bartos, P; Bartunkova, J; Chovanec, J; Cibula, D; Fucikova, J; Galluzzi, L; Hassan, HIB; Hein, A; Hraska, M; Hrnciarova, T; Kieszko, D; Klat, J; Knapp, P; Madry, R; Mallmann, P; Markowska, J; Melichar, B; Minar, L; Pecen, L; Pluta, M; Rob, L; Spacek, J; Spisek, R; Streb, J; Valha, P; Wimberger, P, 2021)		0.62
"DCVAC/OvCa combined with chemotherapy had a favorable safety profile in patients with platinum-sensitive ovarian cancer."( Dendritic cell-based immunotherapy (DCVAC/OvCa) combined with second-line chemotherapy in platinum-sensitive ovarian cancer (SOV02): A randomized, open-label, phase 2 trial.
Bartos, P; Bartunkova, J; Chovanec, J; Cibula, D; Fucikova, J; Galluzzi, L; Hassan, HIB; Hein, A; Hraska, M; Hrnciarova, T; Kieszko, D; Klat, J; Knapp, P; Madry, R; Mallmann, P; Markowska, J; Melichar, B; Minar, L; Pecen, L; Pluta, M; Rob, L; Spacek, J; Spisek, R; Streb, J; Valha, P; Wimberger, P, 2021)		0.62
"This study reports the safety, tolerability, MTD, recommended phase II dose (RP2D), pharmacokinetic/pharmacodynamic profile, and preliminary antitumor activity of ceralasertib combined with carboplatin in patients with advanced solid tumors."( Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.
Berges, A; Cheung, SYA; Clack, G; Dean, E; El-Khouiery, A; Felicetti, B; Frewer, P; Goldwin, A; Hollingsworth, SJ; Irurzun-Arana, I; Jones, GN; Krebs, MG; Lau, A; Lopez, J; Pierce, AJ; Postel-Vinay, S; Smith, SA; Soria, JC; Stephens, C; Yap, TA, 2021)		0.62
"The RP2D for ceralasertib plus carboplatin was established as ceralasertib 40 mg once daily on days 1-2 administered with carboplatin AUC5 every 3 weeks, with pharmacokinetic and pharmacodynamic studies confirming pharmacodynamic modulation and preliminary evidence of antitumor activity observed."( Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.
Berges, A; Cheung, SYA; Clack, G; Dean, E; El-Khouiery, A; Felicetti, B; Frewer, P; Goldwin, A; Hollingsworth, SJ; Irurzun-Arana, I; Jones, GN; Krebs, MG; Lau, A; Lopez, J; Pierce, AJ; Postel-Vinay, S; Smith, SA; Soria, JC; Stephens, C; Yap, TA, 2021)		0.62
"To observe the early efficacy and toxicity of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer (mCRPC)."( [Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer].
Bai, GC; He, ZS; Jin, J; Song, Y; Yu, W, 2021)		0.62
" They were given the chemotherapy of docetaxel combined with carboplatin."( [Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer].
Bai, GC; He, ZS; Jin, J; Song, Y; Yu, W, 2021)		0.62
"This report is a case series study of docetaxel combined with carboplatin in the treatment of mCRPC reported in China and the conclusions are representative."( [Clinical efficacy of docetaxel combined with carboplatin in patients with metastatic castration-resistant prostate cancer].
Bai, GC; He, ZS; Jin, J; Song, Y; Yu, W, 2021)		0.62
" This phase III study investigated the efficacy and safety of poly (ADP-ribose) polymerase inhibitor veliparib in combination with conventional chemotherapy for advanced sqNSCLC (NCT02106546)."( Veliparib in Combination With Platinum-Based Chemotherapy for First-Line Treatment of Advanced Squamous Cell Lung Cancer: A Randomized, Multicenter Phase III Study.
Ansell, P; Bach, BA; Bar, J; Bentsion, D; Bernabe, R; Byers, LA; Clingan, P; Dunbar, M; Glasgow, J; Govindan, R; Guclu, SZ; He, L; Huang, X; Mazieres, J; Novello, S; Ramalingam, SS; Sehgal, V; Syrigos, K; Szilasi, M; Vokes, EE; Zvirbule, Z, 2021)		0.62
" However, the clinical significance of immune checkpoint inhibitors combined with chemotherapy in elderly patients with NSCLC has not yet been fully understood."( Clinical impact of pembrolizumab combined with chemotherapy in elderly patients with advanced non-small-cell lung cancer.
Chihara, Y; Goto, Y; Hibino, M; Hiranuma, O; Iwasaku, M; Kaneko, Y; Kijima, T; Morimoto, K; Morimoto, Y; Nakao, A; Takayama, K; Takeda, T; Takeshita, M; Takumi, C; Uchino, J; Yamada, T; Yamaguchi, H; Yokoi, T, 2021)		0.62
"The RP2D of selinexor was 60 mg QW in combination with CT."( Selinexor in combination with carboplatin and paclitaxel in patients with advanced solid tumors: Results of a single-center, multi-arm phase Ib study.
Carter, BW; Colen, R; Fu, S; Gong, J; Hong, DS; Janku, F; Karp, DD; McQuinn, L; Meric-Bernstam, F; Milton, DR; Naing, A; Piha-Paul, SA; Shah, J; Stephen, BA; Sulovic, S; Thein, KZ; Tsimberidou, A; Yap, TA, 2022)		0.72
" Recently, immune checkpoint inhibitors, combined with chemotherapy, as the first-line treatment for extensive-stage (ES)-SCLC have shown improvement in clinical outcomes."( Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience.
Ahn, BC; Cho, BC; Hong, MH; Kim, HR; Lee, S; Lim, SM; Shim, HS, 2022)		0.72
"Atezolizumab, combined with etoposide and carboplatin, showed efficacy and safety in our real-world data."( Efficacy and safety of atezolizumab, in combination with etoposide and carboplatin regimen, in the first-line treatment of extensive-stage small-cell lung cancer: a single-center experience.
Ahn, BC; Cho, BC; Hong, MH; Kim, HR; Lee, S; Lim, SM; Shim, HS, 2022)		0.72
" Four canine melanoma cell lines were treated in vitro with rapamycin and everolimus as sole treatment or combined with carboplatin."( Investigation of the effects of mTOR inhibitors rapamycin and everolimus in combination with carboplatin on canine malignant melanoma cells.
Bernard, S; Mutsaers, AJ; Poon, AC; Tam, PM, 2021)		0.62
"When combined with carboplatin chemotherapy, rapamycin or everolimus treatment was overall synergistic in reducing cell viability."( Investigation of the effects of mTOR inhibitors rapamycin and everolimus in combination with carboplatin on canine malignant melanoma cells.
Bernard, S; Mutsaers, AJ; Poon, AC; Tam, PM, 2021)		0.62
"Inhibition of mTOR by rapalogs, such as rapamycin and everolimus combined with carboplatin chemotherapy may have activity in canine melanoma."( Investigation of the effects of mTOR inhibitors rapamycin and everolimus in combination with carboplatin on canine malignant melanoma cells.
Bernard, S; Mutsaers, AJ; Poon, AC; Tam, PM, 2021)		0.62
"In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status."( Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study.
Aghajanian, C; Ansell, PJ; Birrer, MJ; Bookman, MA; Coleman, RL; Dinh, MH; Fleming, GF; Friedlander, M; Kaufmann, SH; Levine, DA; Moore, KN; O'Malley, DM; Okamoto, A; Reid, TJ; Sehgal, V; Shahin, MS; Spirtos, NM; Steffensen, KD; Swisher, EM, 2022)		0.72
"Our prospective, open-label, single-arm phase II study investigated the safety and efficacy of DCVAC/LuCa (dendritic cell vaccines for lung cancer) combined with standard carboplatin/pemetrexed in advanced non-squamous (nsq) non-small-cell lung cancer (NSCLC)."( Safety and efficacy of dendritic cell-based immunotherapy (DCVAC/LuCa) combined with carboplatin/pemetrexed for patients with advanced non-squamous non-small-cell lung cancer without oncogenic drivers.
Cao, S; Han, B; Ling, X; Wang, H; Xu, J; Zhang, B; Zhang, X; Zhong, H; Zhong, R, 2022)		0.72
" The patient benefited from immunotherapy combined with chemotherapy."( Successful treatment using immunotherapy in combination with chemotherapy for metastatic squamous cell carcinoma of unknown primary origin with bulky abdominal mass: A case report.
Jin, LF; Shen, WZ; Zhang, M; Zhao, M, 2021)		0.62
" By performing NGS for patients and targeting immune-related positive predictors, immunotherapy combined with chemotherapy may prolong the overall survival of patients."( Successful treatment using immunotherapy in combination with chemotherapy for metastatic squamous cell carcinoma of unknown primary origin with bulky abdominal mass: A case report.
Jin, LF; Shen, WZ; Zhang, M; Zhao, M, 2021)		0.62
"This detailed preclinical investigation, including pharmacokinetics/pharmacodynamics and dose-schedule optimizations, of AZD6738/ceralasertib alone and in combination with chemotherapy or PARP inhibitors can inform ongoing clinical efforts to treat cancer with ATR inhibitors."( ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib.
Bargh-Dawson, H; Brown, E; Gerrard, J; Hughes, AM; Jones, GN; Lau, A; O'Connor, MJ; Odedra, R; Wallez, Y; Wijnhoven, PWG; Wilson, Z; Young, LA, 2022)		0.72
" Second mitochondrial activator of caspase (SMAC) mimetics are the most widely used IAP antagonists currently being tested in clinical trials as a monotherapy and in combination with different chemotherapeutic drugs to target different types of cancer."( Efficacy of birinapant in combination with carboplatin in targeting platinum‑resistant epithelial ovarian cancers.
Dibernardo, G; Memarzadeh, S; Moatamed, NA; Neal, A; Raheseparian, N; Singh, T, 2022)		0.72
"While some clinical studies have shown that PD-1 and PD-L1 can also be an effective neoadjuvant treatment for early-stage non-small cell lung cancer (NSCLC), no evidence has been available for the use of the PD-1 inhibitor sintilimab combined with chemotherapy as a neoadjuvant treatment for potentially resectable NSCLC in the Chinese population."( Interim analysis of the efficiency and safety of neoadjuvant PD-1 inhibitor (sintilimab) combined with chemotherapy (nab-paclitaxel and carboplatin) in potentially resectable stage IIIA/IIIB non-small cell lung cancer: a single-arm, phase 2 trial.
Guo, Y; Lin, X; Liu, Y; Ma, K; Ma, X; Qiu, S; Shao, G; Sun, C; Wang, X; Xu, Y; Yang, Z; Zhang, P, 2023)		0.91
"We conducted a phase Ib dose confirmation study to determine safety and early efficacy signals of varlitinib in combination with chemotherapy (paclitaxel ± carboplatin) ± subcutaneous trastuzumab."( Phase Ib Dose-Finding Study of Varlitinib Combined with Weekly Paclitaxel With or Without Carboplatin ± Trastuzumab in Advanced Solid Tumors.
Chee, CE; Goh, BC; Lee, MX; Lee, SC; Lim, JSJ; Lim, SE; Ow, S; Soo, RA; Sundar, R; Tan, DSP; Wang, L; Wong, ALA; Yong, WP, 2022)		0.72
" Romidepsin (Ro) and brentuximab vedotin (Bv), combined with ifosfamide, carboplatin, and etoposide (ICE) has not been significantly studied in PTCL."( Use of ifosfamide, carboplatin and etoposide in combination with brentuximab vedotin or romidepsin based on CD30 positivity in relapsed/refractory peripheral T-cell lymphoma.
Gentille, C; Joshi, J; Pingali, SR; Randhawa, J; Sarfraz, H; Shah, S, 2022)		0.72
"The aim of this prospective, pilot, single-arm phase II trial was to evaluate the safety and efficacy of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC)."( A phase II study of anlotinib combined with etoposide and platinum-based regimens in the first-line treatment of extensive-stage small cell lung cancer.
Hu, Z; Liao, J; Liu, C; Sun, S; Wang, H; Wang, J; Wu, X; Yu, H; Zhang, Y; Zhao, X, 2022)		0.72
"BRCA-Mutated Advanced Breast Cancer (BROCADE3) is a phase 3 study, evaluating veliparib in combination with carboplatin/paclitaxel with continuation as monotherapy if carboplatin/paclitaxel is discontinued in patients with germline BRCA1/2 mutation-associated, advanced human epidermal growth factor receptor 2-negative breast cancer."( Exposure-Response Model With Time-Varying Predictors to Estimate the Effects of Veliparib in Combination With Carboplatin/Paclitaxel and as Monotherapy: Veliparib Phase 3 Study in BRCA-Mutated Advanced Breast Cancer (BROCADE3) Trial.
Eckert, D; Joshi, R; Menon, R; Mensing, S; Nuthalapati, S; Ratajczak, CK; Stodtmann, S; Xiong, H, 2022)		0.72
"The effect of bevacizumab combined with chemotherapy on the expression of stromal cell-derived factor-1 (SDF-1) and receptor CXCR4 in epithelial ovarian cancer tumor cells and its prognosis are unknown."( Effect of bevacizumab combined with chemotherapy on SDF-1 and CXCR4 in epithelial ovarian cancer and its prognosis.
Ma, C, 2022)		0.72
"This study aimed to compare the efficacy of albumin-bound paclitaxel combined with carboplatin (Nab-TC) with that of traditional solvent-based paclitaxel combined with carboplatin (TC) as neoadjuvant chemotherapy (NAC) regimens for primary epithelial ovarian cancer."( Efficacy evaluation of albumin-bound paclitaxel combined with carboplatin as neoadjuvant chemotherapy for primary epithelial ovarian cancer.
Fan, L; Han, Y; Wang, H; Wu, X, 2022)		0.72
" The primary objective was to determine the recommended phase 2 dose of crenigacestat combined with other anticancer agents (gemcitabine/cisplatin or gemcitabine/carboplatin)."( A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors.
Anderson, B; Azaro, A; Benhadji, KA; Cassier, PA; Massard, C; Oakley, G; Pant, S; Yu, D; Yuen, E, 2022)		0.72
"This study demonstrated that the Notch inhibitor, crenigacestat, combined with different anticancer agents (gemcitabine, cisplatin, and carboplatin) was poorly tolerated and resulted in disappointing clinical activity in patients with advanced or metastatic solid tumors."( A phase 1b study of crenigacestat (LY3039478) in combination with gemcitabine and cisplatin or gemcitabine and carboplatin in patients with advanced or metastatic solid tumors.
Anderson, B; Azaro, A; Benhadji, KA; Cassier, PA; Massard, C; Oakley, G; Pant, S; Yu, D; Yuen, E, 2022)		0.72
"Given its promising efficacy, safety profile and durability, anlotinib combined with chemotherapy deserves further investigation as first-line anticancer therapy in ES-SCLC (NCT: 04684017)."( Safety and efficacy of anlotinib in combination with standard chemotherapy as first-line treatment for extensive-stage small cell lung cancer: A multi-center, prospective study (ACTION-2).
Chen, L; Chen, Y; Deng, P; Dong, Y; Han, B; Kong, T; Liu, D; Qian, F; Yang, H; Zhang, B; Zhang, W; Zhang, Y, 2022)		0.72
"Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy (nICT) or chemoradiotherapy (nICRT) has been tested in resectable esophageal cancer."( Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis.
Chen, J; Dang, J; Li, S; Liu, T; Wang, H, 2022)		0.72
"Clinical trials have shown that trastuzumab (H) and pertuzumab (P) combined with chemotherapy as neoadjuvant therapy increased pathological complete response (pCR) rate of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer."( Real-world study of trastuzumab and pertuzumab combined with chemotherapy in neoadjuvant treatment for patients with HER2-positive breast cancer.
Liu, Y; Ma, X; Ren, X; Song, T; Yang, R; Zhang, W; Zhang, X; Zhou, X, 2022)		0.72
" We report that chemotherapy combined with a programmed death-1 (PD-1) inhibitor was effective in treating metastatic female urethral squamous cell carcinoma."( Chemotherapy combined with immunotherapy in primary female urethral squamous cell carcinoma: a case report.
Bai, H; Han, H; Shi, H; Wang, F, 2022)		0.72
" We conducted an investigator initiated, single-center, open-label, prospective phase 1 study evaluating the safety and efficacy of CFZ in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) eligible patients with R/R DLBCL (NCT01959698)."( Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL.
Anampa-Guzmán, A; Block, A; Darrall, A; DeMarco, J; Ghione, P; Groman, A; Hernandez-Ilizaliturri, FJ; Hutson, A; Johnson, M; Kader, A; Kostrewa, J; Lund, I; Mavis, C; McWhite, K; Mohr, A; Nichols, J; Przespolewski, E; Sait, SJ; Sundaram, S; Thomas, R; Torka, P; Wong, J, 2023)		0.91
" The aim of our study was to determine the efficiency and safety of tislelizumab combined with carboplatin-paclitaxel as a front-line therapy for patients with metastatic or recurrent endometrial cancer."( Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study.
Chen, JL; Gao, FF; Liu, NF; Sui, XC; Tang, YD; Zhang, TT; Zhang, XL, 2022)		0.72
"Tislelizumab combined with carboplatin-paclitaxel was used as a front-line therapy, had a beneficial effect and was safe for patients with metastatic or recurrent endometrial cancer."( Tislelizumab Combined with Carboplatin-Paclitaxel for Treatment of Metastatic or Recurrent Endometrial Cancer: a Retrospective Clinical Study.
Chen, JL; Gao, FF; Liu, NF; Sui, XC; Tang, YD; Zhang, TT; Zhang, XL, 2022)		0.72
"Our results indicate that IPAT combined with carboplatin at low doses was more effective at reducing proliferation, inducing apoptosis and causing cellular stress than IPAT or carboplatin alone."( Ipatasertib, an oral AKT inhibitor, in combination with carboplatin exhibits anti-proliferative effects in uterine serous carcinoma.
Bae-Jump, V; Burkett, WC; Deng, B; Newton, MA; Secord, AA; Sun, W; Zhao, Z; Zhou, C, 2023)		0.91
" AZD5305 alone or in combination with platinum delayed visceral metastasis, ultimately extending the lifespan of OC-PDX-bearing mice."( The PARP1 Inhibitor AZD5305 Impairs Ovarian Adenocarcinoma Progression and Visceral Metastases in Patient-derived Xenografts Alone and in Combination with Carboplatin.
Albertella, MR; Bani, MR; Decio, A; Dellavedova, G; Formenti, L; Ghilardi, C; Giavazzi, R; Leo, E; Staniszewska, AD; Wilson, J, 2023)		0.91
"We aimed to investigate the pathological changes, clinicopathological correlation and prognostic factors of neoadjuvant programmed cell death 1 (PD-1) blockade camrelizumab combined with carboplatin and nab-paclitaxel (CCNP) which we have proved its effectiveness in previous research for resectable esophageal squamous cell carcinoma (ESCC)."( Pathological response and prognostic factors of neoadjuvant PD-1 blockade combined with chemotherapy in resectable oesophageal squamous cell carcinoma.
Chen, S; Chen, W; Cheng, C; Feng, S; Guo, F; Jiang, Z; Wang, H; Wang, Q; Wang, X; Wu, T; Xu, Z; Yang, S; Yang, W, 2023)		0.91
" The purpose of this study was to explore the efficacy and safety of programmed cell death 1 (PD-1) blockade combined with ICE regimen (P-ICE) in the treatment of R/R DLBCL patients."( PD-1 blockade combined with ICE regimen in relapsed/refractory diffuse large B-cell lymphoma.
Bai, B; Gao, Y; He, Y; Huang, C; Huang, H; Ping, L; Shi, L; Wang, X, 2023)		0.91
"The Atezo-Brain study evaluated atezolizumab combined with chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) with untreated brain metastases, a population traditionally excluded from trials."( Phase II Trial of Atezolizumab Combined With Carboplatin and Pemetrexed for Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer With Untreated Brain Metastases (Atezo-Brain, GECP17/05).
Blasco, A; Bruna, J; De Castro, J; Estival, A; Felip, E; Guirado, M; Huidobro, G; Juan, O; López, R; Massutí, B; Mosquera, J; Nadal, E; Navarro, V; Pereira, E; Rodríguez-Abreu, D; Simó, M; Sullivan, I; Vilariño, N, 2023)		0.91
" Carfilzomib, an irreversible proteasome inhibitor, can overcome acquired rituximab-chemotherapy resistance and, when combined with R-ICE, improves outcomes in patients with R/R DLBCL."( Population Pharmacokinetics and Pharmacodynamics of Carfilzomib in Combination with Rituximab, Ifosfamide, Carboplatin, and Etoposide in Adult Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma.
Burke, SM; Ghasemi, M; Goey, AKL; Hernandez-Ilizaliturri, FJ; Lin, LH; Mager, DE; Mavis, CK; Nichols, JR; Torka, P, 2023)		0.91
" Further research is needed to identify sources of variability in response to treatment with carfilzomib in combination with R-ICE."( Population Pharmacokinetics and Pharmacodynamics of Carfilzomib in Combination with Rituximab, Ifosfamide, Carboplatin, and Etoposide in Adult Patients with Relapsed/Refractory Diffuse Large B Cell Lymphoma.
Burke, SM; Ghasemi, M; Goey, AKL; Hernandez-Ilizaliturri, FJ; Lin, LH; Mager, DE; Mavis, CK; Nichols, JR; Torka, P, 2023)		0.91
" In this prospective cohort study, we investigated the efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin (Apa+ddTCb) vs dose-dense paclitaxel plus carboplatin regimens alone (ddTCb) in neoadjuvant therapy for locally advanced TNBC."( Efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin in neoadjuvant therapy for locally advanced triple-negative breast cancer: A prospective cohort study with propensity-matched analysis.
Chai, Y; He, M; Jiang, M; Li, Q; Liu, J; Luo, Y; Ma, F; Ou, K; Qi, L; Wang, X; Wang, Y; Xu, B; Yuan, P; Zhang, P, 2024)		1.44
" Here, we describe 2 cases of locally advanced oral cancer treated with first-line immune checkpoint inhibitors in combination with targeted therapy and chemotherapy."( Efficacy of first-line immunization combined with antiangiogenesis treatment and chemotherapy for the treatment of tongue cancer: A case report.
Chen, C; Gao, F; Liu, Y; Lv, L; Su, L; Xu, B; Zhao, L, 2023)		0.91
"To compare the efficacy of paclitaxel liposomes combined with carboplatin and paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer and assess their effects on serum human epididymis protein 4 (HE4), CA125, CA199, matrix metalloproteinase-2 (MMP2), MMP-7, and MMP-9 levels."( Comparison of paclitaxel liposomes combined with carboplatin versus paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer.
Chen, D; Chen, H; Tan, X; Zou, S, 2023)		0.91
"In this observational study, 102 patients with advanced ovarian cancer were assigned to receive paclitaxel liposomes combined with carboplatin (Group A) or paclitaxel combined with carboplatin (Group B)."( Comparison of paclitaxel liposomes combined with carboplatin versus paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer.
Chen, D; Chen, H; Tan, X; Zou, S, 2023)		0.91
"Paclitaxel liposomes combined with carboplatin displayed better efficacy in the treatment of advanced ovarian cancer than paclitaxel combined with carboplatin, which might be attributable to reductions in serum marker levels and the occurrence of adverse events."( Comparison of paclitaxel liposomes combined with carboplatin versus paclitaxel combined with carboplatin in the treatment of advanced ovarian cancer.
Chen, D; Chen, H; Tan, X; Zou, S, 2023)		0.91

Bioavailability

3a is aqueous soluble, orally bioavailable across multiple species. It demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide (TMZ) and in an MX-1 breast cancer xenograft model.

ExcerptReferenceRelevance
" The low bioavailability (4 to 12%) and the gastrointestinal side effects observed did not warrant further studies with oral administration."( Clinical pharmacokinetics of carboplatin.
van der Vijgh, WJ, 1991)		0.28
"Several novel platinum (IV) mixed ammine/amine dicarboxylate dichlorides of general structure [Pt(IV)Cl2(OCOY)2NH3(XNH2)], where Y is aliphatic or aromatic and X is alicyclic or aliphatic, known to be particularly well absorbed following oral administration, were evaluated by that route for their antitumor activity."( Preclinical antitumor activity of orally administered platinum (IV) complexes.
Casazza, AM; Crosswell, AR; Rose, WC; Schurig, JE, 1993)		0.29
"Marimastat is an orally bioavailable inhibitor of matrix metalloproteinases."( Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer.
Anderson, IC; Eder, JP; Goffin, JR; Johnson, BE; Lynch, TJ; Shapiro, GI; Shipp, M; Skarin, AT; Supko, JG, 2005)		0.33
" In addition, 3a is aqueous soluble, orally bioavailable across multiple species, and demonstrated good in vivo efficacy in a B16F10 subcutaneous murine melanoma model in combination with temozolomide (TMZ) and in an MX-1 breast cancer xenograft model in combination with either carboplatin or cyclophosphamide."( Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer.
Bontcheva-Diaz, V; Bouska, JJ; Donawho, CK; Frost, DJ; Gandhi, VB; Giranda, VL; Gong, J; Johnson, EF; Klinghofer, V; Liu, X; Luo, Y; Marsh, KC; Olson, AM; Osterling, DJ; Penning, TD; Shi, Y; Zhu, GD, 2009)		0.35
" In addition, 22b is orally bioavailable across multiple species, crosses the blood-brain barrier, and appears to distribute into tumor tissue."( Optimization of phenyl-substituted benzimidazole carboxamide poly(ADP-ribose) polymerase inhibitors: identification of (S)-2-(2-fluoro-4-(pyrrolidin-2-yl)phenyl)-1H-benzimidazole-4-carboxamide (A-966492), a highly potent and efficacious inhibitor.
Bontcheva-Diaz, V; Bouska, JJ; Buchanan, FG; Bukofzer, GT; Donawho, CK; Frost, DJ; Fry, EH; Gandhi, VB; Giranda, VL; Gong, J; Johnson, EF; Klinghofer, V; Liu, X; Luo, Y; Marsh, KC; Olson, AM; Osterling, DJ; Park, CH; Penning, TD; Rodriguez, LE; Shi, Y; Thomas, S; Zhu, GD, 2010)		0.36
"Following IP administration, bevacizumab was rapidly absorbed and bioavailability was 92."( Evaluation of combined bevacizumab and intraperitoneal carboplatin or paclitaxel therapy in a mouse model of ovarian cancer.
Balthasar, JP; Bernacki, RJ; Shah, DK; Veith, J, 2011)		0.37
"Satraplatin is a novel platinum agent with favorable clinical attributes including oral bioavailability and lack of significant treatment-associated neuropathy and nephropathy."( Retrospective analysis of satraplatin in patients with metastatic urothelial cancer refractory to standard platinum-based chemotherapy.
Bajorin, DF; Camacho, LH; Chiorean, EG; Galsky, MD; Hong, DS; Mulkerin, D; Oh, WK; Seng, S, 2011)		0.37
"Satraplatin is an orally bioavailable platinum analog with preclinical activity in cisplatin resistant models and clinical activity in adults with refractory cancers."( The plasma and cerebrospinal fluid pharmacokinetics of the platinum analog satraplatin after intravenous administration in non-human primates.
Balis, FM; Cruz, R; Fox, E; Marcus, L; McCully, C; McNiff, E; Meyer, T; Murphy, R; Warren, KE; Widemann, BC, 2012)		0.38
" DCP showed favourable bioavailability and stability in vivo, and the recommended Phase II dosage for DCP-containing chemotherapy is 450 mg/m(2)."( Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results.
Guan, ZZ; Guo, Y; Huang, H; Jiang, WQ; Li, S; Liao, H; Yang, XQ; Zhan, J; Zou, BY, 2013)		0.39
" Thus, this report describes a potential strategy for maximizing the brain bioavailability and therapeutic efficacy of chemotherapeutic drugs."( Dual kinin B1 and B2 receptor activation provides enhanced blood-brain barrier permeability and anticancer drug delivery into brain tumors.
Côté, J; Fortin, D; Gobeil, F; Lepage, M; Neugebauer, W; Savard, M, 2013)		0.39
" Following confirmation of mAb-PA bioavailability and target efficacy in vivo, the antitumor efficacy of mAb-PA in multiple Ovatar tumor models was examined and the response was found to depend on PAPP-A expression."( A novel neutralizing antibody targeting pregnancy-associated plasma protein-a inhibits ovarian cancer growth and ascites accumulation in patient mouse tumorgrafts.
Bale, LK; Becker, MA; Conover, CA; Haluska, P; Oxvig, C, 2015)		0.42
"AXL1717 is an orally bioavailable IGF-1R pathway modulator that has been shown to have anti-tumoral effects."( A phase I pilot study of the insulin-like growth factor 1 receptor pathway modulator AXL1717 in combination with gemcitabine HCl and carboplatin in previously untreated, locally advanced, or metastatic non-small cell lung cancer.
Bergqvist, M; Bergström, S; Brandén, E; Ekman, S; Harmenberg, J; Holgersson, G; Jerling, M; Klockare, M; Koyi, H; Larsson, O; Lundström, KL; Ringbom, M, 2015)		0.42
"Niclosamide has shown activity against ovarian cancer in vitro; however, it has low bioavailability in vivo."( Niclosamide Analogs for Treatment of Ovarian Cancer.
Arend, RC; Buchsbaum, DJ; Chettiar, S; Gangrade, A; Hassmann, CJ; Hidalgo, B; Li, PK; Regan, N; Straughn, JM; Walters Haygood, CL, 2015)		0.42
"Veliparib is a potent, orally bioavailable PARP inhibitor that enhances efficacy of DNA-damaging chemotherapeutic agents."( A phase 1 study evaluating the pharmacokinetics and preliminary efficacy of veliparib (ABT-888) in combination with carboplatin/paclitaxel in Japanese subjects with non-small cell lung cancer (NSCLC).
Fujiwara, Y; Giranda, V; Hashiba, H; Horinouchi, H; Kanda, S; Kitazono, S; Mizugaki, H; Nokihara, H; Qian, J; Shepherd, SP; Tamura, T; Xiong, H; Yagishita, S; Yamamoto, N, 2015)		0.42
" The oral bioavailability of carboplatin/DOCA complex and native carboplatin were calculated as 24."( Metronomic chemotherapy using orally active carboplatin/deoxycholate complex to maintain drug concentration within a tolerable range for effective cancer management.
Alam, F; Byun, Y; Choi, JU; Chung, SW; Kim, IS; Kim, SW; Kim, SY; Lee, DS; Mahmud, F, 2017)		0.46
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019)		0.51
" In addition, Oxy210 displays encouraging drug-like properties, including chemical scalability, metabolic stability and oral bioavailability in mice."( Inhibition of Non-Small Cell Lung Cancer Cells by Oxy210, an Oxysterol-Derivative that Antagonizes TGFβ and Hedgehog Signaling.
Parhami, F; Stappenbeck, F; Tang, LY; Wang, F; Zhang, YE, 2019)		0.51
" We hypothesized that the orally bioavailable TORC1/2 kinase inhibitor TAK228 would have activity against MYC-driven medulloblastoma."( TORC1/2 kinase inhibition depletes glutathione and synergizes with carboplatin to suppress the growth of MYC-driven medulloblastoma.
Alt, J; Archer, TC; Eberhart, CG; Hanaford, AR; James, M; Maynard, RE; Mesirov, J; Park, Y; Pham, K; Pomeroy, SL; Poore, B; Raabe, EH; Slusher, BS; Tamayo, P, 2021)		0.62
"AZD6738 (ceralasertib) is a potent and selective orally bioavailable inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase."( ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib.
Bargh-Dawson, H; Brown, E; Gerrard, J; Hughes, AM; Jones, GN; Lau, A; O'Connor, MJ; Odedra, R; Wallez, Y; Wijnhoven, PWG; Wilson, Z; Young, LA, 2022)		0.72

Dosage Studied

Adaptive dosing of carboplatin based on GFR overestimated the dose required to achieve the target carboplati AUC in pediatric patients with brain tumors treated with concurrent lobradimil. A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin'scarboplatin dosing formula with 14-day oral etoposide.

ExcerptRelevanceReference
" Cisplatin/5-fluorouracil (5-FU) is the most frequently used combination regimen, but neurotoxicity, ototoxicity, and renal toxicity limit repeated dosing (for long-term treatment of responding patients) and dose intensification."( Chemotherapy of head and neck cancer.
Forastiere, AA, 1992)		0.28
" It is suggested that pharmacokinetically based dosing schemes may be advantageous and that randomized trials should be performed to test this hypothesis."( Future directions with carboplatin: can therapeutic monitoring, high-dose administration, and hematologic support with growth factors expand the spectrum compared with cisplatin?
Calvert, AH; Gore, ME; Newell, DR, 1992)		0.28
"5 x 10(9)/l) and platelet recovery (> 50 x 10(9)/l) were 33 and 28 days, respectively, with similar findings for all dosage levels."( Escalating sequential high-dose carboplatin and etoposide with autologous marrow support in children with relapsed solid tumors.
Bowman, LC; Brenner, MK; Mirro, J; Santana, VM; Schell, MJ; Thompson, EI; Williams, R, 1992)		0.28
" Based on recent data that suggest chronic administration of oral etoposide is superior to single daily dosing every 3 to 4 weeks, and the failure of previous trials to evaluate etoposide's activity in cisplatin-resistant malignancies, we have begun a phase II trial of chronic, low-dose oral etoposide in patients with clinically defined, platinum-resistant ovarian cancer."( Exploring the use of chronic low-dose oral etoposide in ovarian cancer: is there a role for this "new drug" in the management of platinum-refractory disease?
Almadrones, L; Barakat, R; Curtin, J; Hakes, T; Hoskins, W; Jones, W; Lewis, JL; Markman, M; Reichman, B; Rubin, S, 1992)		0.28
" Aim of the following study was dosage optimisation of the applicated carboplatin."( [Dose-finding study for hyperfractionated, accelerated radiotherapy plus simultaneous carboplatin administration in patients with locoregionally advanced head and neck cancer].
Brockmann, WP; Hartwein, J; Kehrl, W; Zschaber, R, 1992)		0.28
" The dosage of carboplatin was adjusted for creatinine clearance."( Carboplatin, methotrexate, and vinblastine in patients with bladder cancer who were ineligible for cisplatin-based chemotherapy.
Albanell, J; Bellmunt, J; Carulla, J; De Torres, J; Gallego, OS; Lopez, M; Morote, J; Ribas, A; Solé, LA; Vicente, P, 1992)		0.28
"Carboplatin dosing by AUC will lead to more predictable toxicity, and increasing carboplatin AUC above 5 to 7 mg/mL x minutes does not improve the likelihood of response but does increase myelotoxicity."( Relationships between carboplatin exposure and tumor response and toxicity in patients with ovarian cancer.
Burroughs, JN; Canetta, RM; Egorin, MJ; Goldbloom, EP; Goodlow, JL; Jodrell, DI; Langenberg, P; Tan, S; Wiltshaw, E, 1992)		0.28
"(-)-(R)-2-Aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato++ +)platinum(II) monohydrate (DWA2114R), cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP) were compared for their antitumor effects and nephrotoxicity-inducing activities at the same dosage (1/8, 1/4, 1/3, 1/2, 2/3 or 3/4 of the LD10 or LD10) on the basis of their intravenous lethal doses in mice."( Antitumor effects of three platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato)-platinum (II) monohydrate (DWA2114R), cis-diammine-(1,1-cyclobutanedicarboxylato)platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (CDDP)
Akamatsu, K; Endo, K; Koizumi, K; Koizumi, M; Matsumoto, T; Mitsui, H; Morikawa, K, )		0.13
" Also, r-HuEPO may allow modest dosage increments in chemotherapy or the addition of abdominopelvic radiotherapy."( Recombinant human erythropoietin in patients with ovarian carcinoma and anaemia secondary to cisplatin and carboplatin chemotherapy: preliminary results.
Belli, F; Cowan, R; James, RD; Welch, R; Wilkinson, PM, 1992)		0.28
"Carboplatin disposition was studied in 18 pediatric patients with cancer over a dosage range of 400 to 700 mg/m2 given on an alternate-day schedule (total doses of 1200 to 2100 mg/m2) with high-dose etoposide."( The pharmacokinetics of high-dose carboplatin in pediatric patients with cancer.
Madden, T; Rodman, JH; Santana, VM; Sunderland, M, 1992)		0.28
" Thus, increase in dosage was stopped at an etoposide dose of 160 mg/m2."( Determining carboplatin/etoposide dosage in extensive stage small-cell lung cancer (SCLC).
Achterrath, W; Drings, P; Goerg, C; Havemann, K; Tessen, HW; Wolf, M, 1991)		0.28
"Between February 1986 and July 1988 a total of 21 children aged 1 to 16 years with malignant germ cell tumours (MGCT), 18 with either metastatic disease or unresectable primary tumour, received the JEB regimen - carboplatin dosage calculated from the EDTA glomerular filtration rate (approximately 600 mg m-2), etoposide 120 mg m-2 daily x 3, and bleomycin 15 mg m-2 weekly."( 'JEB'--a carboplatin based regimen for malignant germ cell tumours in children.
Broadbent, V; Horwich, A; Levitt, J; McElwain, TJ; Meller, ST; Mott, M; Oakhill, A; Pinkerton, CR; Pritchard, J, 1990)		0.28
" Relationships between pharmacokinetics (area under the curve) and pharmacodynamics (extent of myelosuppression or extent of existing kidney failure) have allowed the development of equations for rational dosage reduction."( Clinical pharmacokinetics of carboplatin.
van der Vijgh, WJ, 1991)		0.28
" Increases in exposure time of K562 cells to DWA2114R resulted in progressive shifting of the dose-response curve to the left, or more effective cell growth inhibition of the cells."( Antitumor activities of new platinum compounds, DWA2114R, NK121 and 254-S, against human leukemia cells sensitive or resistant to cisplatin.
Kobayashi, H; Miyachi, H; Ogawa, T; Takemura, Y, 1991)		0.28
") was administered just prior to an alkylating agent, the combination treatment produced significantly more tumor cell killing across the dosage range of each alkylating agent tested compared with the alkylating agent alone."( Modulation of alkylating agents by etanidazole and Fluosol-DA/carbogen in the FSaIIC fibrosarcoma and EMT6 mammary carcinoma.
Bubley, G; Coleman, CN; Eder, JP; Frei, E; Herman, TS; Holden, SA; Tanaka, J; Teicher, BA, 1991)		0.28
" Patients were treated intravenously at an initial dosage of 270 mg/m2 with dosage adjustments to 340, 200 or 135 based on observed toxicity."( Second-line treatment of advanced measurable ovarian cancer with iproplatin: a Southwest Oncology Group study.
Alberts, DS; Baker, LH; Goodwin, JW; Green, S; Hanson, K; Hines, HE; Pierce, HI; Thigpen, JT; Weiss, G, 1991)		0.28
" Carboplatin does not have significant renal toxicity when used at conventional dosage in patients with germ cell tumours."( The effect of carboplatin on renal function in patients with metastatic germ cell tumours.
Horwich, A; Mason, MD; Nicholls, J, 1991)		0.28
"Fifteen patients with advanced urothelial cancer were treated with carboplatin 300 mg/m2, methotrexate 30 mg/m2, and vinblastin 3 mg/m2 on day 1 and the same dosage of methotrexate and vinblastin on days 15 and 22."( Carboplatin, methotrexate and vinblastin (Carbo-MV) for advanced urothelial cancer. A phase II trial.
Kienzer, H; Klocker, J; Pont, J; Prüger, J; Schumer, J, 1991)		0.28
" When cyclophosphamide and thiotepa were given in the same schedule, 10-fold increases in tumor cell killing were evident on tumor excision assay over the dosage ranges."( Lonidamine as a modulator of alkylating agent activity in vitro and in vivo.
Epelbaum, R; Frei, E; Herman, TS; Holden, SA; Liu, SD; Teicher, BA, 1991)		0.28
" We conclude from the toxicities observed, that combinations of carboplatin with cisplatin may have advantages over either drug alone in certain clinical situations; and that further study of platinum-DNA adducts may shed light on platinum dose-response relationships."( Dose-escalation study of carboplatin (day 1) and cisplatin (day 3): tolerance and relation to leukocyte and buccal cell platinum--DNA adducts.
Christian, MC; den Engelse, L; Gill, I; Grunberg, S; Kortes, V; Michael, C; Muggia, FM; Parker, RJ; Reed, E; Terheggen, PM, 1991)		0.28
"1% of PAC patients required a dosage reduction at the second course (P = ."( Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.
Bruzzone, M; Carnino, F; Chiara, S; Conte, PF; Donadio, M; Facchini, V; Fioretti, P; Foglia, G; Gadducci, A; Gallo, L, 1991)		0.28
" In addition, the toxicities of the combination therapies were lower than what was produced by the highest dosage of CDDP (4 mg/kg/day for 5 days)."( Advantages in combination chemotherapy using cisplatin and its analogues for human testicular tumor xenografts.
Hida, S; Okada, K; Yoshida, O, 1990)		0.28
" This approach does not assume that the underlying dose-response curve is steep; nor does it assume that maximally dose-intense regimens are clinically appropriate in all situations."( Selecting drug combinations based on total equivalent dose (dose intensity)
Korn, EL; Simon, R, 1990)		0.28
"The principles of dose-response and combination chemotherapy were basic to the design of the initial curative standard-dose treatment regimens for leukemias, lymphomas, and testis cancer."( A phase I-II study of cyclophosphamide, thiotepa, and carboplatin with autologous bone marrow transplantation in solid tumor patients.
Burke, J; Eder, JP; Elias, A; Frei, E; Hunt, M; Schnipper, LE; Schryber, SM; Shea, TC; Siegel, R; Teicher, BA, 1990)		0.28
" Initial dosage was 320 mg/m2 infused over 24 h; in the absence of hematologic toxicity, subsequent doses were escalated to 400 mg/m2."( A phase II trial of carboplatin (CBDCA) in small-cell and non-small-cell lung cancer with correlation to in vitro analysis of cytotoxicity.
Batist, G; Brantley, P; Dmitrovsky, E; Edison, M; Gazdar, AF; Ihde, DC; Mulshine, JL; Seifter, EJ; Tsai, CM; Veach, SR, 1990)		0.28
" However, this Pt is already bound to protein and unlikely to be cytotoxic to reinfused haemopoietic stem cells, so bone marrow reinfusion can be safely performed at 48 h after repeated dosing of carboplatin on three consecutive days."( Pharmacokinetics of carboplatin at a dose of 750 mg m-2 divided over three consecutive days.
de Vries, EG; Mulder, NH; Mulder, PO; Scaf, AH; Sleijfer, DT; Uges, DR, 1990)		0.28
" We conclude that although carboplatin is ototoxic, clinically significant deafness does not occur with conventional dosing and routine audiometric monitoring is therefore unnecessary."( Carboplatin is ototoxic.
Atkinson, CH; Colls, BM; Fitzharris, BM; Kennedy, IC, 1990)		0.28
" injections of CDDP (5 mg/kg) or CBDCA (50 mg/kg) were given over 2 months to 288 male B6D2F1 mice standardized by an alternation of 12 hr of light and 12 hr of darkness at any one of three circadian dosing times (0, 8 or 16 hr after light onset--HALO)."( Stable circadian mechanisms of toxicity of two platinum analogs (cisplatin and carboplatin) despite repeated dosages in mice.
Boughattas, NA; Fournier, C; Hecquet, B; Lemaigre, G; Lévi, F; Mathé, G; Reinberg, A; Roulon, A, 1990)		0.28
" The drug was administered at a starting dosage of 400 mg/m2 IV every 28 days."( A phase II trial of carboplatin for recurrent or metastatic squamous carcinoma of the uterine cervix: a Southwest Oncology Group study.
Alberts, DS; Boutselis, JG; Green, S; Hannigan, EV; Surwit, EA; Wallace, DL; Weiss, GR, 1990)		0.28
" The dose-response curve produced by carboplatin on neuroblastoma spheroids displayed a pronounced shoulder in the low-dose region; this phenomenon was not seen with cis-DDP."( The relative effectiveness of analogues of cisplatin in the experimental chemotherapy of human non-small-cell lung cancer and neuroblastoma grown as multicellular spheroids.
Adam, J; Kaye, SB; Russell, J; Wheldon, TE, 1989)		0.28
"Thrombocytopenia, the dose-limiting toxicity of carboplatin, is manageable and predictable with the dosing equation: Dose (mg/m2) = (0."( A novel pharmacodynamically based approach to dose optimization of carboplatin when used in combination with etoposide.
Abrams, JS; Aisner, J; Belani, CP; Egorin, MJ; Eisenberger, M; Hiponia, D; Van Echo, DA, 1989)		0.28
" Other factors, such as prior radiotherapy, may also be important in the dosing of CBDCA in pretreated patients."( Phase II study of carboplatin in recurrent ovarian cancer: severe hematologic toxicity in previously treated patients.
Beller, U; Blum, RH; Canetta, R; Colombo, N; Green, M; Meyers, M; Piccart, M; Speyer, JL; Wernz, JC; Widman, T, 1989)		0.28
" Since the dose intensity of cisplatin is important in achieving optimal results, it is probable that carboplatin dosage is an important factor in maximizing efficacy, particularly in platinum-sensitive tumors."( Optimal dosing with carboplatin.
Ozols, RF, 1989)		0.28
" No significant dose-response relationship was demonstrated in this heterogeneous group of patients."( A dose escalation study of carboplatin and ifosfamide in advanced ovarian cancer.
Coleman, RE; Gallagher, CJ; Harper, PG; Wiltshaw, E, 1989)		0.28
" The results of the 13 patients receiving the PE regimen were retrospectively compared to those of 24 patients who received the conventional PAC schedule (cisplatin, Adriamycin and cyclophosphamide at a dosage of 50, 50 and 750 mg/m2, respectively)."( Efficacy of adjuvant carboplatin-epirubicin chemotherapy in advanced ovarian cancer after radical surgery.
Lahousen, M; Lehnert, M; Petru, E; Pickel, H; Stettner, H, 1989)		0.28
"In the preceding study, no teratological effects against rat fetuses were observed when carboplatin, an oncostatic platinum coordination complex, was dosed to their dams from days 7 to 17 of gestation at a dose level of 4 mg/kg/day."( Teratogenic effects of carboplatin, an oncostatic drug, administered during the early organogenetic period in rats.
Ishikawa, K; Kai, S; Kawano, S; Kohmura, H; Makihara, Y; Ohta, S; Takahashi, N, 1989)		0.28
"A dosage formula has been derived from a retrospective analysis of carboplatin pharmacokinetics in 18 patients with pretreatment glomerular filtration rates (GFR) in the range of 33 to 136 mL/min."( Carboplatin dosage: prospective evaluation of a simple formula based on renal function.
Boxall, FE; Burnell, M; Calvert, AH; Gore, ME; Gumbrell, LA; Judson, IR; Newell, DR; O'Reilly, S; Siddik, ZH; Wiltshaw, E, 1989)		0.28
" Increased dosage did not increase the response rate."( Phase II study of carboplatin in locally advanced and metastatic transitional cell carcinoma of the urinary bladder.
Fossa, SD; Parø, G; Raabe, NK, 1989)		0.28
" The overall in vitro response rate (defined as less than 50% survival of tumor colony forming units) for 254-S was observed in 10/29 and 20/30 evaluable specimens isolated freshly from NSCLC patients with continuous exposure at 1 and 10 micrograms/ml, respectively, indicating a positive dose-response relationship."( Antitumor activity of a new platinum compound (glycolate-o,o') diammineplatinum (II) (254-S), against non-small cell lung carcinoma grown in a human tumor clonogenic assay system.
Kanzawa, F; Matsushima, Y; Nakagawa, K; Nakano, H; Saijo, N; Sasaki, Y; Takahashi, H, )		0.13
" Carboplatin was administered intravenously by two dosing schedules at 300 mg/m2 and 400 mg/m2."( [A phase II study of carboplatin to bronchogenic carcinoma of the lung. Carboplatin Cooperative Study Group for Lung Carcinoma].
, 1988)		0.27
" Carboplatin was administered by three dosing schedule of 300 mg/m2, 400 mg/m2 and 450 mg/m2."( [A phase II study of carboplatin in small cell lung cancer].
Furuse, K; Ishiwata, K; Komatsu, H; Minoda, S; Nemoto, E; Nishikawa, H; Saito, T; Saotome, K; Tani, Y; Tsutsumi, M, 1988)		0.27
" Cisplatin (100 mg/m2) was administered with mannitol, or at a twofold larger total dosage (50 mg/m2 per day for 4 days) in a 3% saline infusion."( Carboplatin (CBDCA), iproplatin (CHIP), and high dose cisplatin in hypertonic saline evaluated for tubular nephrotoxicity.
Dodge, RK; Forastiere, AA; Goren, MP; Horowitz, ME; Kamen, BA; Pratt, CB; Viar, MJ; Wright, RK, 1987)		0.27
" CHIP and carboplatin gave similar dose-response curves, both being much less toxic than cis-platin."( An in vitro study comparing the cytotoxicity of three platinum complexes with regard to the effect of thiol depletion.
Brock, AP; Smith, E, 1988)		0.27
" These animals were then mated under the consecutive administration of this drug and the females confirmed to be copulated were further dosed from day 0 through 7 of gestation."( [Reproduction studies of carboplatin (I)--Intravenous administration to rats prior to and in the early stages of pregnancy].
Chikazawa, H; Ishikawa, K; Kadota, T; Kai, S; Kawano, S; Kohmura, H; Kondo, H; Kuroyanagi, K; Ohta, S; Takeuchi, Y, 1988)		0.27
" The recommended iv dose of carboplatin as a single agent in previously untreated patients is 400-500 mg/m2; dosage must be reduced in patients with decreased renal function, low initial platelet count, or extensive prior chemotherapy or radiation therapy."( Carboplatin: a new cisplatin analog.
Cluxton, RJ; Pruemer, JM; Woloschuk, DM, 1988)		0.27
" As thrombocytopenia was dose-limiting, we have developed an equation for modification of the dose of CBDCA from the relationship between the relative dose and percent reduction at platelet count nadir: Dosage (mg/m2) = (Ccr/m2/5."( Prediction of hematologic toxicity of carboplatin by creatinine clearance rate.
Eguchi, K; Fujiwara, Y; Minato, K; Miura, K; Saijo, N; Sakurai, M; Sasaki, Y; Shinkai, T; Taguchi, J; Tamura, T, 1987)		0.27
" In our pilot study, aiming at optimizing the dosage of this drug in a combination regimen with other chemotherapics, we planned to evaluate the existence of drug related damage on cochleo-vestibular structures."( Evaluation of the cochleovestibular function in patients treated with carboplatin for ovarian carcinoma.
Bruzzone, M; Chiara, S; Cordone, G; Foglia, G; Madaro, M; Ragni, N; Repetto, P; Ruvolo, M, 1986)		0.27
" 5-FU dosage was decreased in ten patients (36%) for grade 2 or greater stomatitis or diarrhea."( A phase I-II trial of carboplatin and 5-fluorouracil combination chemotherapy in advanced carcinoma of the head and neck.
Forastiere, AA; Goren, MP; Kudla-Hatch, V; Natale, RB; Takasugi, BJ; Vogel, WC, 1987)		0.27
" From these correlations, we developed equations to calculate carboplatin dosage for any patient based on that patient's creatinine clearance, body surface area, pretreatment platelet count, desired platelet nadir, and status of prior chemotherapy."( Prospective validation of a pharmacologically based dosing scheme for the cis-diamminedichloroplatinum(II) analogue diamminecyclobutanedicarboxylatoplatinum.
Aisner, J; Egorin, MJ; Forrest, A; Olman, EA; Van Echo, DA; Whitacre, MY, 1985)		0.27
"Cisplatin (Platinol) has an important dose-response relationship in ovarian cancer."( High-dose cisplatin therapy in ovarian cancer.
Ozols, RF; Young, RC, 1985)		0.27
"Pharmacokinetic measurements to monitor and design cytotoxic treatments in cancer patients are being used more and more in order to optimize dosage and administration schedules."( Pharmacokinetic studies in lung cancer patients.
Cattaneo, MT; Piazza, E; Varini, M, 1984)		0.27
" A similar dose-response curve was obtained with melphalan for each of the four xenografts, despite previous treatment with an alkylating agent in two of the patients from whom the xenografts originated."( Cell survival in four ovarian carcinoma xenografts following in vitro exposure to melphalan, cisplatin and cis-diammine-1,1-cyclobutane dicarboxylate platinum II (CBDCA,JM8).
Jones, AC; Steel, GG; Wilson, PA, 1984)		0.27
" Since total body clearance is proportional to CCr, platelet reduction is proportional to AUC, and total body clearance = dosage/AUC, we have derived an equation to calculate a dosage that will produce a desired reduction in platelet count."( Pharmacokinetics and dosage reduction of cis-diammine(1,1-cyclobutanedicarboxylato)platinum in patients with impaired renal function.
Aisner, J; Egorin, MJ; Olman, EA; Thompson, BW; Tipping, SJ; Van Echo, DA; Whitacre, MY, 1984)		0.27
" Patients were treated at six dosage levels ranging from 200-550 mg/m2 every five weeks."( A phase I trial of cis-diammine-1,1-cyclobutane dicarboxylate platinum II (Carboplatin, CBDCA, JM-8) with a single dose every five week-schedule.
Brunner, KW; Cavalli, F; Goldhirsch, A; Joss, RA; Kaplan, S; Sessa, C, 1984)		0.27
" Carboplatin, dosed to a target area under the concentration-time curve of 5, 7, 9, or 11 mg/mL."( Pharmacokinetics of paclitaxel and carboplatin in combination.
Aisner, J; Belani, CP; Engstrom, C; Erkmen, K; Hiponia, D; Kearns, CM; Ramanathan, R; Trenn, MR; Zacharski, D; Zuhowski, M, 1995)		0.29
" Using area under the curve dosing for carboplatin, it was demonstrated that this agent could be combined with paclitaxel (175 mg/m2 in a 3-hour infusion) with acceptable toxicity."( Current status of chemotherapy for ovarian cancer.
Ozols, RF, 1995)		0.29
" The steep dose-response curves described by Hryniuk and Levin [5] make them the ideal substances for dose escalation."( [Dose intensified carboplatin monotherapy in advanced ovarian cancer].
Illiger, HJ; Jackisch, C; Nitz, U; Schiller, E; Weise, W, 1994)		0.29
" It appears that this regimen, at the dosage and schedule studied, possesses only modest activity in patients with breast cancer, while being relatively atoxic."( Combination chemotherapy with carboplatin, cyclophosphamide and fluorouracil in advanced breast cancer.
Closon, MT; Kains, JP; Schallier, D; Tijtgat, J; Verbeke, L, )		0.13
" There is a suggestion of a dose-response effect with both paclitaxel and carboplatin."( Paclitaxel and carboplatin with and without filgrastim support in patients with metastatic non-small cell lung cancer.
Aisner, J; Belani, CP; Engstrom, C; Hiponia, D, 1995)		0.29
" The dosage of paclitaxel was escalated from 75 to 225 mg/m2."( A phase I study of ifosfamide/carboplatin/etoposide/paclitaxel in advanced lung cancer.
Carey, RW; Elias, AD; Grossbard, ML; Jacobs, C; Jauss, S; Kwiatkowski, DJ; Lynch, TJ; Shulman, LN; Strauss, GM; Sugarbaker, DJ, 1995)		0.29
" Of 50 evaluable patients, five of the six major responses were observed at paclitaxel doses of 175 mg/m2 and above, which suggests a dose-response relationship for paclitaxel in NSCLC."( Dose-finding and sequencing study of paclitaxel and carboplatin in non-small cell lung cancer.
Beijnen, JH; Dalesio, O; Giaccone, G; Huizing, M; Koolen, M; Pinedo, HM; Postmus, PE; ten Bokkel Huinink, WW; van Zandwijk, N; Vermorken, JB, 1995)		0.29
" Moreover, what results can be expected if one uses effective ip chemotherapy with the standard dose in conjunction with the PBSCT-HDCT combination? Especially, if one can contact the residual tumor in the intraperitoneal cavity most likely to have a recurrence with a drug at an extremely high concentration, enabling a massive dose to the intraperitoneal cavity comparable to the standard dosage by vas internal administration with equivalent blood concentration, distant metastases may also be prevented."( [High-dose chemotherapy (HDCT) with peripheral blood stem cell transplantation (PBSCT) in ovarian cancer patients with poor prognosis].
Hayakawa, S; Sato, S; Yajima, A, 1995)		0.29
" A clear dose-response relationship was evident between the number of CD34+ cells per kilogram infused between the number of CD34+ cells per kilogram infused and neutrophil and platelet engraftment kinetics."( An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy.
Allen, C; Birch, R; Hazelton, B; Palmer, P; Schwartzberg, L; Weaver, CH; West, W, 1995)		0.29
" A dose-response relationship was not apparent with the mini-ICE regimen; however, among patients receiving maxi-ICE, a dose-response relationship was suggested in those patients responding to anthracycline-based chemotherapy."( Ifosfamide/carboplatin/etoposide chemotherapy for metastatic breast cancer with or without autologous hematopoietic stem cell transplantation: evaluation of dose-response relationships.
Elfenbein, GJ; Fields, KK; Perkins, JB, 1995)		0.29
" Since ICE has substantial activity in a number of malignancies, but significant renal morbidity, real-time pharmacokinetic-guided dosing may reduce treatment-related toxicity."( High-dose ifosfamide, carboplatin, and etoposide pharmacokinetics: correlation of plasma drug levels with renal toxicity.
Andersen, J; Antman, K; Elias, A; Frel, E; Holden, S; Rosowsky, A; Schwartz, G; Tretyakov, O; Wheeler, C; Wright, JE, 1995)		0.29
" Dosing of this agent based solely upon the patients body surface area is therefore not accurate enough; the GFR, and thus the clearance of carboplatin differ in each patient irrespective of the body area."( The use of the Calvert formula to determine the optimal carboplatin dosage.
Beijnen, JH; Maes, RA; Rodenhuis, S; ten Bokkel Huinink, WW; van Warmerdam, LJ, 1995)		0.29
" There appears to be a dose-response relationship: two partial responses (12%) were observed among 17 patients assigned to the lower-dose groups, whereas six (50%) of 12 evaluable patients in the higher-dose groups achieved partial responses."( A phase I study of carboplatin and paclitaxel in non-small cell lung cancer: a University of Colorado Cancer Center study.
Bunn, PA; Kelly, K, 1995)		0.29
" Carboplatin did not appear to add to the hematologic toxicities observed, and the paclitaxel/carboplatin combination could be dosed every 3 weeks."( Paclitaxel 3-hour infusion given alone and combined with carboplatin: preliminary results of dose-escalation trials.
Israel, V; Jeffers, S; McRae, A; Muggia, FM; Natale, R; Rogers, M; Vafai, D; Zaretsky, S, 1995)		0.29
" A second major finding was a dose-response relationship for rhu IL-3: the two higher doses employed, 250 and 500 micrograms, offered more effective platelet protection than the lower dose employed, 50 micrograms."( A phase I trial of cyclosphosphamide and carboplatinum combined with interleukin-3 in women with advanced-stage ovarian cancer.
Cohen, C; Demakos, E; Hochster, H; Mandeli, J; Oette, D; Runowicz, C; Sorich, J; Speyer, JL; Wadler, S; Wallach, R, 1995)		0.29
" Dosage adjustment based on isotopic determination of glomerular filtration rate has been proposed, but its ambulatory use is not yet conceivable."( Prediction of carboplatin clearance from standard morphological and biological patient characteristics.
Boneu, A; Brunner, V; Bugat, R; Canal, P; Chatelut, E; Chevreau, C; Houin, G; Pujol, A; Roché, H, 1995)		0.29
"This formula for the determination of carboplatin clearance can permit individualized determination of carboplatin dosage in adults by simply multiplying the calculated carboplatin clearance by the area under the curve for the desired dosage administration."( Prediction of carboplatin clearance from standard morphological and biological patient characteristics.
Boneu, A; Brunner, V; Bugat, R; Canal, P; Chatelut, E; Chevreau, C; Houin, G; Pujol, A; Roché, H, 1995)		0.29
" Carboplatin was given as an outpatient on day 1 at a dosage based on the formula: Dose (mg/m2) = (0."( Phase II study of carboplatin and edatrexate (10-EdAM) with leucovorin rescue for patients with recurrent squamous cell carcinoma of the head and neck.
Benner, SE; Dimery, IW; Esparaz, B; Frenning, D; Guillory-Perez, C; Hong, WK; Huber, MH; Lippman, SM; Shirinian, M, 1994)		0.29
" Using AUC-based dosing compensates for variations in renal function between and within individual patients."( Dose optimisation of carboplatin in adults.
Calvert, AH, )		0.13
" Extensive data for carboplatin, and more limited results with cisplatin, indicate that there is significant inter-patient pharmacokinetic variability such that adaptive dosing may be necessary for the optimal use of these drugs."( The comparative pharmacokinetics and pharmacodynamics of cisplatin and carboplatin in paediatric patients: a review.
Bin, P; Boddy, AV; English, MW; Newell, DR; Pearson, AD; Price, L; Tilby, MJ, )		0.13
" Dosage reduction was required in 15% of courses and escalation in 5% of courses."( A phase II trial of zeniplatin in metastatic melanoma.
Birkhofer, M; Bishop, J; Green, M; Ketelbey, W; Olver, I; Peters, W; Rastogi, R; Toner, G; Zimet, A, 1995)		0.29
" These results compare favourably with other combined modality studies, using multiple radiotherapy fractions with cisplatin-based combinations and dosage reduction for patients staged in more anatomical detail."( Therapy for small cell lung cancer using carboplatin, ifosfamide, etoposide (without dose reduction), mid-cycle vincristine with thoracic and cranial irradiation.
Burt, P; Hicks, F; Leahy, B; Lorigan, P; Prendiville, J; Stout, R; Thatcher, N, 1994)		0.29
" The scatter in the data was estimated and used in a Monte-Carlo computer simulation to derive the following five-level dosing scheme."( A dosing scheme for carboplatin in adult cancer patients based upon pre-infusion renal function and platelet count.
Adams, M; Fish, RG; Griffiths, H; James, K; Mason, M; Shelley, MD, 1994)		0.29
" Several factors provided the rationale for this study: paclitaxel plus cisplatin has been shown to be superior to standard treatment with cyclophosphamide plus cisplatin; carboplatin is equally effective and less toxic than cisplatin in ovarian cancer; paclitaxel plus carboplatin could potentially produce less nonhematologic toxicity than cisplatin plus paclitaxel; dosing of carboplatin based on the area under the carboplatin plasma concentration vs."( Carboplatin and Taxol (paclitaxel) in advanced ovarian carcinoma.
Ozols, RF, 1994)		0.29
" Since the toxicities of either drug largely depended upon circadian dosing time, such a pharmacokinetic study was performed following injection of either Pt complex at a time of low (16 h after light onset-HALO), intermediate (0 HALO) or high (8 HALO) toxicity."( Comparative pharmacokinetics of oxaliplatin (L-OHP) and carboplatin (CBDCA) in mice with reference to circadian dosing time.
Boughattas, NA; Bouzouita, K; Bruguerolle, B; Fournier, C; Hecquet, B; Lévi, F; Omrane, B; Trabelsi, H, 1994)		0.29
" Cisplatin was administered every 4 weeks for a total of 10 courses, courses 1 to 5 at a dosage of 100 mg/m2 and courses 6 to 10 at 30 mg/m2."( Long-term follow-up of the first randomized study of cisplatin versus carboplatin for advanced epithelial ovarian cancer.
Fisher, C; Fryatt, I; Gore, ME; Taylor, AE; Wiltshaw, E, 1994)		0.29
" IFN dosage should be reduced to improve tolerance."( Carboplatin and alpha-2b interferon intraperitoneal combination as first-line treatment of minimal residual ovarian cancer. A pilot study.
Cardone, A; Conforti, S; Facchini, G; Frasci, G; Iaffaioli, RV; Mastrantonio, P; Persico, G; Tortoriello, A, 1994)		0.29
"In order to perform melphalan dosage adjustment, the linearity of melphalan kinetics was studied, in the case of previous carboplatin administration."( [Effect of carboplatin on the pharmacokinetics of melphalan administered intravenously].
Ardiet, C; Biron, P; Bouffet, E; Brunat-Mentigny, M; Nasri, F; Philip, I; Tranchand, B, 1994)		0.29
" The validated limited sampling model provides a starting point for future pharmacokinetic studies in a larger population of patients, which might lead to more insight into the relationships with the pharmacodynamic outcome of carboplatin and may help in achieving more rational dosing of patients on the basis of an AUC determination."( Validation of a limited sampling model for carboplatin in a high-dose chemotherapy combination.
Beijnen, JH; Maes, RA; Rodenhuis, S; van Tellingen, O; van Warmerdam, LJ, 1994)		0.29
" In addition, for each patient, the predicted nadir count (obtained by rearranging the University of Maryland single-agent carboplatin dosing formula) was compared with the actual observed nadir count, received and relative received dose intensities were calculated, and carboplatin exposure intensity was defined."( Modeling toxicity and response in carboplatin-based combination chemotherapy.
Burroughs, JN; Canetta, RM; Egorin, MJ; Jodrell, DI; Novak, MJ; Pater, JL; Reyno, LM; Sridhara, R; Swenerton, KD, 1994)		0.29
"Agents with broad cytotoxic activity, steep linear log dose-response relationships, relative non-cross-resistance, and nonoverlapping nonhematologic toxicities can be combined to create new high-dose combination regimens."( High-dose ifosfamide/carboplatin/etoposide with autologous hematopoietic stem cell support: safety and future directions.
Antman, KH; Ayash, LJ; Elias, AD; Frei, E; Mazanet, R; McCauley, M; Schnipper, L; Schwartz, G; Tepler, I; Wheeler, C, 1994)		0.29
" A course of radiotherapy consisted of 5 consecutive fractions (3 Gy per fraction, 1 fraction per day) for a total dosage of 15 Gy per course."( Alternated approach with local irradiation and combination chemotherapy including cisplatin or carboplatin plus epirubicin and etoposide in intermediate stage non-small cell lung cancer.
Anania, C; Casaretti, R; Comella, G; Comella, P; Curcio, C; Daponte, A; Maiorino, A; Musetta, G; Scoppa, G, 1994)		0.29
" IC50 values were obtained from dose-response curves after fitting the data by the linear quadratic equation, F = exp[-(alpha D + beta D2)]."( Comparative evaluation of cisplatin and carboplatin sensitivity in endometrial adenocarcinoma cell lines.
Grénman, R; Grénman, S; Kulmala, J; Rantanen, V, 1994)		0.29
" The clinical development of carboplatin has in turn been strongly influenced by the studies of its pharmacokinetics, with pharmacokinetically guided dosing now being standard in many cancer centres and also being widely used in current clinical trials."( Platinum complexes in cancer medicine: pharmacokinetics and pharmacodynamics in relation to toxicity and therapeutic activity.
Calvert, H; Judson, I; van der Vijgh, WJ, 1993)		0.29
" Dosage was adjusted to reach active AUC (area under the plasma concentration versus time curve) of ultrafilterable carboplatin."( Pharmacokinetics of carboplatin in a patient suffering from advanced ovarian carcinoma with hemodialysis-dependent renal insufficiency.
Canal, P; Chatelut, E; De Forni, M; Gualano, V; Houin, G; Rostaing, L; Suc, JM; Ton-That, H; Vissac, T, 1994)		0.29
"Optimal dosing of intraperitoneal-administered carboplatin with a dwell-time is not possible because of the differences in recovery."( Intraperitoneal-administered carboplatin in patients with ovarian cancer; influence of a dwell-time on toxicity and response.
Beijnen, JH; Dubbelman, AC; McVie, JG; ten Bokkel Huinink, WW; van Warmerdam, LJ, 1994)		0.29
" Carboplatin dosing by the area under the curve (AUC) may minimize thrombocytopenia."( Ifosfamide, carboplatin, and etoposide plus granulocyte-macrophage colony-stimulating factor: a phase I study with apparent activity in non-small-cell lung cancer.
Comis, R; Haas, N; Kilpatrick, D; Krigel, RL; Langer, C; Padavic, K; Palackdharry, CS, 1994)		0.29
" Continuous infusion carboplatin did not alter carboplatin clearance or adversely effect glomerular filtration rate during a second course, showing the feasibility of this alternative dosage strategy to enhance therapeutic effects."( Pharmacokinetics and acute renal effects of continuously infused carboplatin.
Murry, DJ; Rodman, JH; Sandlund, JT; Stricklin, LM, 1993)		0.29
" In our view, carboplatin is a more appropriate agent than cisplatin for inclusion in high-dose chemotherapy schedules with autologous bone marrow rescue, and our results support the concept of calculating dose escalation on the basis of the area under the dose-response curve using the Calvert formula, rather than on surface area."( Carboplatin in the treatment of advanced breast cancer: a phase II study using a pharmacokinetically guided dose schedule.
O'Brien, ME; Smith, IE; Talbot, DC, 1993)		0.29
" The efficacy of carboplatin could be optimized by adapting the dosage to the glomerular filtration rate, which is a more accurate method than extrapolation from the serum creatinine or creatinine clearance values."( Carboplatin and urothelial tumors.
Bons-Rosset, F; Costa, P; Louis, JF; Mottet-Auselo, N; Navratil, H, 1993)		0.29
"GFR-based carboplatin dosing in children should be feasible and will be evaluated prospectively."( Carboplatin pharmacokinetics in children: the development of a pediatric dosing formula. The United Kingdom Children's Cancer Study Group.
Balmanno, K; Calvert, AH; Keir, M; Lewis, IJ; Newell, DR; Pearson, AD; Pinkerton, CR; Price, L; Stevens, MC; Wyllie, RA, 1993)		0.29
" Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity."( Pharmacokinetic and phase I evaluation of carboplatin in dogs.
Dewhirst, MW; George, SL; Heidner, GL; McEntee, MC; Novotney, CA; Page, RL; Riviere, JE; Thrall, DE; Williams, PL, )		0.13
" However, in vitro data demonstrate a steep dose-response curve to a variety of agents, most notably mitoxantrone."( Phase I clinical and pharmacokinetic study of high-dose mitoxantrone combined with carboplatin, cyclophosphamide, and autologous bone marrow rescue: high response rate for refractory ovarian carcinoma.
Alberts, DS; Dolan, JR; McCloskey, T; McKenzie, RS; Rad, N; Sosman, JA; Stiff, PJ, 1994)		0.29
"Between October 1985 and March 1988, the Childrens Cancer Group entered 117 patients with drug-resistant, recurrent lymphomas and solid tumors, excluding primary central nervous system tumors, into a Phase II trial of carboplatin given intravenously at a dosage of 560 mg/m2 over 1 hour every 4 weeks."( A phase II study of carboplatin in children with recurrent or progressive solid tumors. A report from the Childrens Cancer Group.
Baum, ES; Ettinger, LJ; Gaynon, PS; Hammond, GD; Krailo, MD; Ru, N; Siegel, SE, 1994)		0.29
" The thermal enhancement ratios (TERs) of drug-mediated thrombocytopenia, anaemia and leukopenia were determined from the dose-response curves of the nadir values of the peripheral platelet, RBC and WBC counts."( Haematological toxicity of carboplatin and cisplatin combined with whole body hyperthermia in rats.
Baba, H; Bull, JM; Khokhar, AR; Makino, M; Ohno, S; Siddik, ZH; Stephens, LC; Strebel, FR, 1993)		0.29
" Relative dose intensity was calculated as a fraction of the dosage of a drug in the standard regimen of cyclophosphamide, altretamine, doxorubicin, and platinum (CHAP)."( Importance of multiagent chemotherapy regimens in ovarian carcinoma: dose intensity analysis.
Hryniuk, W; Levin, L; Simon, R, 1993)		0.29
" Using morphological and functional methods it could be shown that the ototoxic damage was by far higher in a group which had received a total dose of 12 kg cisplatin/kg than in a group which had received a dosage of 90 mg carboplat/kg."( [Comparative studies of the ototoxicity of cisplatin and carboplatin].
Delb, W; Federspil, P; Feilen, S; Koch, A, 1993)		0.29
"A continuous 14-day infusion of ifosfamide admixed with carboplatin is feasible in an ambulatory setting with no need for adding mesna for urologic protection and full dosage administration for each agent."( Pilot study of ambulatory infusional ifosfamide admixed with carboplatin.
Anderson, NR; Bern, MM; Coco, F; Gonzalves, L; Lokich, JJ; Moore, C; Zipoli, TE, 1993)		0.29
" One hundred seventeen patients with residual disease of 2 cm or less at second-look laparotomy or laparoscopy were then randomized to receive consolidation therapy, either five further courses of carboplatin at the same dosage or whole-abdominal RT (24 Gy)."( A randomized trial comparing single-agent carboplatin with carboplatin followed by radiotherapy for advanced ovarian cancer: a North Thames Ovary Group study.
Gregory, WM; Lambert, HE; Nelstrop, AE; Rustin, GJ, 1993)		0.29
" The clear relationship between hematologic toxicity and carboplatin systemic exposure supports the use of targeted dosing in further trials of ICE chemotherapy."( Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed solid tumors.
Bowman, LC; Douglass, E; Furman, W; Hudson, M; Marina, NM; Meyer, W; Rodman, J; Santana, VM; Shema, SJ; Wilimas, J, 1993)		0.29
"Patients were assigned to dosage cohorts separately on the basis of prior exposure to the platinum alkylating agents cisplatin or carboplatin (n = 20) or the absence of such exposure (n = 9)."( A phase I study of ifosfamide with Mesna given daily for 3 consecutive days to children with malignant solid tumors.
Avery, L; Bowman, L; Douglass, EC; Marina, N; Meyer, WH; Ochs, J; Pratt, CB; Thompson, EI; Wilimas, J, 1993)		0.29
"Myelosuppression was dose-limiting at the second dosage level (2560 mg/m2/d) for patients previously treated with platinum and at the third dosage level (3072 mg/m2/d) for those not previously treated with platinum."( A phase I study of ifosfamide with Mesna given daily for 3 consecutive days to children with malignant solid tumors.
Avery, L; Bowman, L; Douglass, EC; Marina, N; Meyer, WH; Ochs, J; Pratt, CB; Thompson, EI; Wilimas, J, 1993)		0.29
" The nadir count predicted using the University of Maryland single-agent carboplatin dosing formula was compared with the nadir count observed."( Impact of cyclophosphamide on relationships between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer.
Burroughs, JN; Canetta, RM; Egorin, MJ; Jodrell, DI; Novak, MJ; Pater, JL; Reyno, LM; Sridhara, R; Swenerton, KD, 1993)		0.29
" Received carboplatin dose-intensity underestimates the range of plasma drug exposure resulting from a fixed carboplatin dosing regimen."( Impact of cyclophosphamide on relationships between carboplatin exposure and response or toxicity when used in the treatment of advanced ovarian cancer.
Burroughs, JN; Canetta, RM; Egorin, MJ; Jodrell, DI; Novak, MJ; Pater, JL; Reyno, LM; Sridhara, R; Swenerton, KD, 1993)		0.29
" In total, 158 courses (median: 4, range: 1 through 16; 81 and 58 courses at, respectively, a 40 and 50 to 55 mg/m2 daily dosage of C) were delivered using a multichannel programmable in-time pump (Intelliject, Aguettant) connected to a double lumen implanted venous side-port."( Ambulatory chronotherapy with 5-fluorouracil, folinic acid, and carboplatin for advanced non-small cell lung cancer. A phase II feasibility trial.
Denis, B; Focan, C; Focan-Henrard, D; Kreutz, F; Levi, F, 1995)		0.29
" An individual dosing strategy has been recommended to yield the most optimal exposure, expressed as the area under the concentration-time curve (AUC)."( Evaluation of formulas using the serum creatinine level to calculate the optimal dosage of carboplatin.
Beijnen, JH; Maes, RA; Rodenhuis, S; ten Bokkel Huinink, WW; van Warmerdam, LJ, 1996)		0.29
" Dosage adjustments based on isotopic determination of glomerular filtration rate have been proposed but their ambulatory use is not conceivable."( [Prediction of carboplatin clearance from morphological and biological patient characteristics].
Boneu, A; Bugat, R; Canal, P; Chatelut, E; Chevreau, C; Dezeuze, A; Houin, G; Lavit, M; Pujol, A; Roché, H, 1995)		0.29
" A formula based on renal function has been successfully applied to carboplatin dosing in adults and modified versions have also been proposed for paediatric patients."( Comparison of methods for the estimation of carboplatin pharmacokinetics in paediatric cancer patients.
Boddy, AV; Chatelut, E; Cole, M; Newell, DR; Pearson, AD; Peng, B; Rubie, H, 1995)		0.29
" As carboplatin, in the dosage used, involves no severe acute side-effects and probably few late adverse effects, this regimen constitutes a promising new treatment option in seminoma patients stage I that deserves to be studied in randomized trials."( Adjuvant carboplatin treatment for seminoma clinical stage I.
Brüggeboes, B; Dieckmann, KP; Krain, J; Küster, J, 1996)		0.29
" IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation."( Endometrial cancer cell lines are sensitive to paclitaxel.
Grénman, R; Grénman, S; Kulmala, J; Rantanen, V, )		0.13
" At this dose, severe thrombocytopenia, that necessitated dosage delays, and failure to give subsequent cycles of carboplatin were observed."( Phase I study of pharmacologically based dosing of carboplatin with filgrastim support in women with epithelial ovarian cancer.
Bailey, NP; Calvert, AH; Chapman, F; Craigs, D; Dore-Green, F; Fishwick, K; Ghazal-Aswad, S; Gumbrell, L; Lind, MJ; McCann, E; Middleton, I; Millward, MJ; Oakey, A; Proctor, M; Robson, L; Simmons, D; Sinha, D, 1996)		0.29
" Aggressive dosing of cyclophosphamide and carboplatin could not be maintained for six cycles in the majority (62%) of patients."( Phase I/II study of PIXY321 in combination with cyclophosphamide and carboplatin in the treatment of ovarian cancer.
Garrison, L; Hochster, H; Holland, JF; Mandeli, J; Runowicz, CD; Speyer, JL; Wadler, S, 1996)		0.29
" This treatment safely achieved a greater dose-intensity of carboplatin than would have been achieved with conventional dosing based on body-surface area."( Carboplatin and paclitaxel in ovarian carcinoma: a phase I study of the Gynecologic Oncology Group.
Bookman, MA; Gallion, HH; Hogan, WM; Johnson, SW; Keenan, E; Kilpatrick, D; McGuire, WP; O'Dwyer, P; Ozols, RF; Rowinsky, E, 1996)		0.29
" Sequential dosing protocols, administration of high-dose chemotherapy with peripheral blood progenitor cell support, and other approaches, possibly combining current treatment options, may be necessary to further improve the long-term survival of patients with relapsed NHL."( Dose-intensive ifosfamide for the treatment of non-Hodgkin's lymphoma.
Vose, JM, 1996)		0.29
" Paclitaxel (135 or 175 mg/m2) was administered by 24-hour infusion on day 1, followed by a 1-hour infusion of carboplatin on day 2 (300 mg/m2 or dosed to an area under the concentration-time curve [AUC] of 6 mg/mL."( Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial.
Blanke, C; De Vore, RF; Hande, KR; Johnson, DH; Lewis, M; Murphy, B; Paul, DM; Shyr, Y, 1996)		0.29
" These data suggested that dosing of carboplatin should be determined individually on the basis of renal function, as recommended earlier."( Analysis of thrombocytopenia due to carboplatin combined with etoposide in elderly patients with lung cancer.
Bando, T; Fujimura, M; Kasahara, K; Matsuda, T; Nakatsumi, Y; Shibata, K, 1996)		0.29
" The risk of developing sAML has been estimated to be between 2% and 10%, depending upon the type, duration and dosage of previous therapy (Michels et al, 1985; Shulman, 1993; Robinson & Mertens, 1993; Ballen & Antin, 1993)."( Platinum agents and secondary myeloid leukaemia: two cases treated only with platinum-based drugs.
Catovsky, D; Dainton, MG; Elebute, MO; Gore, M; Min, T; Philpott, NJ; Powles, R; Swansbury, GJ; Treleaven, JG, 1996)		0.29
" Nevertheless, recovery was prompt and opportune dosage reductions avoided severe toxicity in subsequent cycles in most patients."( Treatment of advanced urothelial carcinoma with M-VECA (methotrexate, vinblastine, epirubicin and carboplatin).
Comella, P; De Lena, M; Durini, E; Fiorillo, C; Lorusso, V; Pagliarulo, A; Riccardi, F; Selvaggi, FP, 1996)		0.29
" Because renal excretion is the major variable determining the pharmacokinetics of this drug, a dosing formula based on glomerular filtration rate (GFR) has been proposed and is being increasingly used in carboplatin dosing."( Carboplatin dosing based on measurement of renal function--experience at the Peter MacCallum Cancer Institute.
Bishop, JF; Hicks, R; Johnston, VK; Millward, MJ; Rischin, D; Stokes, KH; Toner, GC; Webster, LK, 1996)		0.29
"To report the experience at a single major oncology centre of carboplatin dosing based on GFR, and comparisons of different methods of measuring renal function for use in this dosing method."( Carboplatin dosing based on measurement of renal function--experience at the Peter MacCallum Cancer Institute.
Bishop, JF; Hicks, R; Johnston, VK; Millward, MJ; Rischin, D; Stokes, KH; Toner, GC; Webster, LK, 1996)		0.29
"Carboplatin dosing using Cr51EDTA clearance to measure GFR was accurate (< 25% difference between planned and measured AUC) in 87% of samples."( Carboplatin dosing based on measurement of renal function--experience at the Peter MacCallum Cancer Institute.
Bishop, JF; Hicks, R; Johnston, VK; Millward, MJ; Rischin, D; Stokes, KH; Toner, GC; Webster, LK, 1996)		0.29
"Carboplatin dosing using a pharmacological formula based on GFR produces accurate targeting of the carboplatin AUC."( Carboplatin dosing based on measurement of renal function--experience at the Peter MacCallum Cancer Institute.
Bishop, JF; Hicks, R; Johnston, VK; Millward, MJ; Rischin, D; Stokes, KH; Toner, GC; Webster, LK, 1996)		0.29
" Dosage in subsequent cycles was adjusted according to hematologic toxicity."( A carboplatin-based regimen for the treatment of patients with advanced transitional cell carcinoma of the urothelium.
Carroll, PR; Ernest, ML; Fippin, LJ; Small, EJ, 1996)		0.29
"The addition of IFN-alpha to induction CT appears to confer a survival benefit to SCLC patients but optimal dosing schedule has yet to be defined."( Interferon alpha-2a and combined chemotherapy as first line treatment in SCLC patients: a randomized trial.
Charitopoulos, K; Dimitriadis, K; Economides, D; Maglaveras, N; Papagiannis, A; Vamvalis, C; Zarogoulidis, K; Ziogas, E, 1996)		0.29
" Carboplatin dosing was escalated and determined using the Calvert formula, and three patients were treated at the initial predicted dose of area under the curve (AUC) 4 mg/mL/min."( A phase I study of gemcitabine and carboplatin in non-small cell lung cancer.
Allerheiligen, S; Carmichael, J; Walling, J, 1996)		0.29
" Therefore, an optimal dosing schedule was not achieved in this trial."( Intravenous carboplatin for recurrent gliomas. A dose-escalating phase II trial.
Chandler, KL; Mack, EE; Malec, M; Page, M; Prados, MD; Rabbitt, J; Warnick, RE, 1996)		0.29
" A clear dose-response relation with respect to response rate and survival was observed."( Pharmacokinetics of paclitaxel and carboplatin in a dose-escalating and dose-sequencing study in patients with non-small-cell lung cancer. The European Cancer Centre.
Bakker, PJ; Beijnen, JH; Bierhorst, FJ; Dalesio, O; Giaccone, G; Huizing, MT; Koolen, MG; Lai, A; Pinedo, HM; Postmus, PE; Rosing, H; ten Bokkel Huinink, WW; van der Vijgh, WJ; van Warmerdam, LJ; van Zandwijk, N; Veenhof, CH; Vermorken, JB, 1997)		0.3
" The etoposide prodrug etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) was administered by infusion using an adaptive dosing strategy."( Etoposide phosphate infusion with therapeutic drug monitoring in combination with carboplatin dosed by area under the curve: a cancer research campaign phase I/II committee study.
Abrahamsen, D; Boddy, A; Brampton, M; Calvert, AH; Lind, M; Newell, D; Porter, D; Robson, L; Thomas, H; Winograd, B, 1996)		0.29
" All patients received paclitaxel 175 mg/m2 as a 3-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 7, every 3 weeks."( Paclitaxel and carboplatin in nonoperable non-small cell lung cancer.
Athanasiadis, A; Fountzilas, G; Kosmidis, P; Mylonakis, N; Samantas, E; Skarlos, D, 1996)		0.29
" The maximum tolerated dose (MTD) was defined as the dosage of 5-FU that achieved 60% grade 3/4 toxicity."( A phase I/II study of leucovorin, carboplatin and 5-fluorouracil (LCF) in patients with carcinoma of unknown primary site or advanced oesophagogastric/pancreatic adenocarcinomas.
Chang, J; Cunningham, D; Gore, M; Hill, A; Hill, M; Moore, H; Nicolson, M; Norman, A; O'Brien, M; Oates, J; Rigg, A; Ross, P; Watson, M, 1997)		0.3
"We have previously reported a 62% response rate and 54% 1-year survival rate for patients with advanced non-small cell lung cancer (NSCLC) treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) by 24-hour infusion in combination with carboplatin, using area under the concentration-time curve dosing (FCCC 93-024)."( Combination paclitaxel (1-hour) and carboplatin (AUC 7.5) in advanced non-small cell lung cancer: a phase II study by the Fox Chase Cancer Center Network.
Alexander, R; Bonjo, CA; Kosierowski, R; Langer, CJ; Litwin, S; McAleer, CA; Millenson, M; O'Dwyer, P; Ozols, R, 1996)		0.29
"A multi-institutional phase II trial of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 225 mg/m2 over 3 hours and carboplatin dosed to an area under the concentration-time curve of 6 by the Calvert formula given preoperatively every 3 weeks for two cycles in patients with intermediate-risk non-small cell lung cancer is described."( Preoperative paclitaxel plus carboplatin for patients with intermediate-risk non-small cell lung cancer.
Ruckdeschel, JC, 1996)		0.29
" All patients received paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 7, every 3 weeks."( Paclitaxel and carboplatin in inoperable non-small cell lung cancer.
Athanasiadis, A; Fountzilas, G; Kosmidis, P; Mylonakis, N; Samantas, E; Skarlos, D, 1996)		0.29
" Further investigation is needed to optimize carboplatin dosage with adaptive control using formulas based on pharmacokinetics and pharmacodynamics."( Chemoradiotherapy in non-small cell lung cancer: paclitaxel/carboplatin/radiotherapy in regionally advanced disease.
Aisner, J; Bahri, S; Belani, CP; Capazolli, MJ; Day, R; Engstrom, C; Hiponia, D; Jett, J, 1996)		0.29
" The purpose of this phase I trial was to determine if granulocyte macrophage colony-stimulating factor (GM-CSF) support allows the dosage of the combination of etoposide and carboplatin to be increased above the previously determined MTD."( Phase I trial of etoposide, carboplatin, and GM-CSF in extensive small-cell lung cancer: a Cancer and Leukemia Group B study (CALGB 8832).
Clamon, GH; Crawford, J; Green, MR; Herndon, JE; Hollis, DR; Luikart, SD; MacDonald, M; Maurer, LH; Ozer, H; Perry, MC; Wright, J, 1997)		0.3
" A number of dosing methods have been described that allow a value for the area under the concentration-time curve to be targeted on the basis of the patient's renal function."( A sequential Bayesian algorithm for dose individualisation of carboplatin.
Begg, EJ; Deely, JJ; Duffull, SB; Robinson, BA, 1997)		0.3
" Furthermore, the relative platinum accumulation was calculated from the total dosage of cisplatin administered."( Distribution of platinum in human gynecologic tissues and lymph nodes after intravenous and intraarterial neoadjuvant chemotherapy.
Ishikawa, H; Kawai, M; Kikkawa, F; Matsuzawa, K; Suganuma, N; Tamakoshi, K; Tomoda, Y, )		0.13
" This trial demonstrates that carboplatin dosed by the Calvert equation and 3-hour paclitaxel can be combined safely at full therapeutic doses for six or more courses in patients with advanced epithelial ovarian cancer."( Paclitaxel combined with carboplatin in the first-line treatment of advanced ovarian cancer: a phase I trial.
Bauknecht, T; Bochtler, H; Diergarten, K; du Bois, A; Köchli, O; Kreienberg, R; Kühnle, H; Luck, HJ; Meerpohl, HG; Möbus, V, 1997)		0.3
" Chemotherapy consisted of paclitaxel 200 mg/m2, given as a 3-hour infusion, and carboplatin dosed to an area under the concentration-time curve of 7 mg x min/mL, administered every 28 days."( Paclitaxel and carboplatin in recurrent or metastatic head and neck cancer: a phase II study.
Athanassiadis, A; Bacoyiannis, H; Daniilidis, J; Fountzilas, G; Kalogera-Fountzila, A; Kosmidis, P; Nikolaou, A; Samantas, E; Skarlos, D; Stathopoulos, G, 1997)		0.3
" Previous pharmacokinetic studies have suggested that the measured area under the plasma carboplatin concentration-time curve is significantly less than that predicted by dosing formulas based on glomerular filtration rates."( A review of the pharmacokinetics and pharmacodynamics of combination carboplatin/paclitaxel.
Calvert, AH, 1997)		0.3
"This double-blind, dose-response study was conducted to assess the safety and efficacy of four oral doses of dolasetron mesylate for preventing acute emesis in cancer patients receiving their first course of moderately emetogenic platinum-containing chemotherapy."( Oral dolasetron mesylate in patients receiving moderately emetogenic platinum-containing chemotherapy. Oral Dolasetron Dose Response Study Group.
Benedict, CR; Figlin, RA; Grote, TH; Hahne, WF; Hesketh, PJ; Karlan, BY; Pendergrass, KB; Pineda, LF; Porter, LL; Reeves, JA, )		0.13
" This study shows that in NSCLC a dose-response effect does not exist between carboplatin dose intensification and response rate cannot be traced."( Intensified carboplatin regimen with GM-CSF support in non-small cell lung cancer (NSCLC). A Hellenic Co-operative Oncology Group Study (HeCOG).
Athanassiadis, A; Fountzilas, G; Klouvas, G; Kosmidis, P; Mylonakis, N; Nicolaides, C; Pavlidis, N; Samantas, E; Skarlos, D, 1997)		0.3
" Dose-response curves for micronuclei in fibroblasts revealed normal distribution with the maximum at 100, 25 and 5 mumol/l after 24, 48 and 72 hours treatment of carboplatin, respectively."( Carboplatin-induced micronuclei formation in non-neuronal cells of rat foetal dorsal root ganglia cultured in vitro and comparison with another anticancer drug--cisplatin.
Jirsová, K; Mandys, V, 1996)		0.29
" bolus of carboplatin at a dosage of 150 (n = 3), 200 (n = 3), or 250 (n = 3) mg/m2 of body surface area."( Hematologic and systemic toxicoses associated with carboplatin administration in cats.
Daniel, GB; Hahn, KA; Legendre, AM; McEntee, MF; Nolan, ML, 1997)		0.3
" At a highest dosage (250 mg/m2), the neutrophil nadir (560 +/- 303 neutrophils/microliters) was observed on day 17 and the platelet count nadir (96,500 +/- 11,815 platelets/microliters) was observed on day 14 after carboplatin administration."( Hematologic and systemic toxicoses associated with carboplatin administration in cats.
Daniel, GB; Hahn, KA; Legendre, AM; McEntee, MF; Nolan, ML, 1997)		0.3
" as a single bolus at a dosage of 200 mg/m2 to clinically normal cats."( Hematologic and systemic toxicoses associated with carboplatin administration in cats.
Daniel, GB; Hahn, KA; Legendre, AM; McEntee, MF; Nolan, ML, 1997)		0.3
" Modifications of dosing schedules and the use of premedication regimens have resulted in better efficacy and more manageable side effects with such combinations."( Overview of current and future chemotherapeutic agents in non-small cell lung cancer.
Natale, RB, 1997)		0.3
" We concluded that the individual dosing strategy based on renal function can be applied with a 5-day schedule as well as a single-day schedule."( Pharmacokinetic study of carboplatin given on a 5-day intravenous schedule.
Ando, M; Ando, Y; Minami, H; Saka, H; Sakai, S; Shimokata, K; Sugiura, S, 1997)		0.3
"Methods included: 1) selective intra-arterial delivery performed with modern microcatheters, 2) pulsatile infusion, and 3) dosage based on local cerebral blood-flow estimation (middle cerebral artery 60%, anterior cerebral artery 20%, posterior cerebral artery 15%, and anterior choroidal artery 5% of the hemispheric blood-flow)."( Intra-arterial carboplatin chemotherapy for brain tumors: a dose escalation study based on cerebral blood flow.
Black, KL; Cloughesy, TF; Gobin, YP; Kabbinavar, F; Kadkhoda, B; Taft, F; Viñuela, F, 1997)		0.3
" The study then progressed to a phase II trial using the maximum tolerated paclitaxel dosage reached during the escalating dose phase."( A phase I-II trial of fixed-dose carboplatin and escalating paclitaxel in advanced ovarian cancer.
Bolis, G; Ferraris, C; Gentile, A; Guarnerio, P; Melpignano, M; Parazzini, F; Presti, M; Scarfone, G; Tateo, S; Villa, A; Zanaboni, F, 1997)		0.3
" All patients received paclitaxel 175 mg/m2 as a three-hour infusion, and carboplatin dosed to an area under the concentration-time curve of seven, every three weeks."( Paclitaxel and carboplatin in inoperable non-small-cell lung cancer: a phase II study.
Andreopoulou, E; Athanasiadis, A; Fountzilas, G; Kosmidis, PA; Mylonakis, N; Pavlidis, N; Samantas, E; Skarlos, D, 1997)		0.3
" The dose-response relationship to paclitaxel and results of comparison with other platinum-based regimens remain to be determined."( Paclitaxel and carboplatin in inoperable non-small-cell lung cancer: a phase II study.
Andreopoulou, E; Athanasiadis, A; Fountzilas, G; Kosmidis, PA; Mylonakis, N; Pavlidis, N; Samantas, E; Skarlos, D, 1997)		0.3
" Appropriate dosage adjustments of warfarin should be performed if an altered response to warfarin is observed."( Enhancement of warfarin response in a patient receiving etoposide and carboplatin chemotherapy.
Hasson, NK; Le, AT; Lum, BL, 1997)		0.3
" Treatment consists of paclitaxel 185 mg/m2 infused over 3 hours on day 1 followed directly by either cisplatin 75 mg/m2 (arm B) or carboplatin dosed to an area under the curve of 6 (arm A)."( Carboplatin plus paclitaxel as first-line chemotherapy in previously untreated advanced ovarian cancer. German AGO Study Group Ovarian Cancer. Arbeitsgemeinschaft Gynäkologische Onkologie.
Bauknecht, T; Costa, S; du Bois, A; Jackisch, C; Lück, HJ; Meier, W; Möbus, V; Nitz, U; Olbricht, S; Richter, B; Schroeder, W; Warm, M, 1997)		0.3
" Substantial interpatient pharmacokinetic variability and narrow therapeutic indexes of the two agents led to the development of several dosing strategies."( Comparative clinical pharmacology of cisplatin and carboplatin.
Murry, DJ, )		0.13
"A recent phase II study by our group documented a response rate of 27% with the combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 175 mg/m2 plus carboplatin dosed to a target area under the concentration-time curve of 7 in patients with advanced non-small cell lung cancer."( Paclitaxel (175 mg/m2) plus carboplatin versus paclitaxel (225 mg/m2) plus carboplatin in non-small cell lung cancer: a randomized study.
Athanassiadis, A; Fountzilas, G; Kosmidis, P; Mylonakis, N; Pavlidis, N; Samantas, E; Skarlos, D, 1997)		0.3
"In this feasibility study, a 3-hour infusion of 225 mg/m2 paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was combined with carboplatin dosed to an area under the concentration-time curve of 6 to treat patients with stage T2N0, T1-2N1, or T3N0-1 (excluding superior sulcus tumors) non-small cell lung cancer."( Induction paclitaxel/carboplatin in early stage non-small cell lung cancer. Bimodality Lung Oncology Team.
Bunn, PA; Crowley, JJ; Ginsberg, RJ; Johnson, DH; Kris, MG; Pisters, KM; Ruckdeschel, JC, 1997)		0.3
" The treatment consisted of three courses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 225 mg/m2 given intravenously over 3 hours and carboplatin dosed to an area under the concentration-time curve of 6, with close monitoring of the lesion by computed tomography or magnetic resonance imaging of the brain after each chemotherapy course."( Paclitaxel/carboplatin chemotherapy as primary treatment of brain metastases in non-small cell lung cancer: a preliminary report.
Fossella, FV; Glisson, BS; Khuri, FR; Komaki, R; Lee, JS; Pisters, KM; Schea, R, 1997)		0.3
" The study design and dosing schedule are discussed in this report."( Paclitaxel/carboplatin plus ifosfamide in non-small cell lung cancer.
Golomb, HM; Hoffman, PC; Masters, G; Mauer, AM; Vokes, EE; Watson, S, 1997)		0.3
"We have treated 26 consecutive chemotherapy-naive patients with stage IIIB/IV non-small cell lung cancer with an innovative regimen based on a 1-hour infusion of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 125 to 250 mg/m2, ifosfamide 3 g/m2 (with mesna), and carboplatin dosed to an area under the concentration-time curve of 5, every 21 days for a total of six cycles in responding or stabilized patients."( Paclitaxel, ifosfamide, and carboplatin for the treatment of stages IIIB and IV non-small cell lung cancer: preliminary results.
Alghisi, A; Bozzola, G; Marini, G; Meriggi, F; Mutti, S; Pascarella, A; Rizzi, A; Zaniboni, A, 1997)		0.3
" Activity for paclitaxel 135 mg/m2 and 200 mg/m2 by 1-hour infusion every 3 weeks in patients with NSCLC, with minimal myelosuppression and the suggestion of a dose-response relationship, has been reported."( Paclitaxel (1-hour) and carboplatin (area under the concentration-time curve 7.5) in advanced non-small cell lung cancer: a phase II study of the Fox Chase Cancer Center and its network.
Bonjo, CA; Langer, CJ; Litwin, S; McAleer, CA; Millenson, M; Ozols, R; Rosvold, E, 1997)		0.3
" Preliminary data also suggest the possibility of a dose-response curve for the combination."( A randomized study of etoposide and carboplatin with or without paclitaxel in the treatment of small cell lung cancer.
Birch, R; Bobo, C; Greco, FA; Hainsworth, JD; Weaver, CH, 1997)		0.3
" In addition, a higher LND dosage was provided on the day of CDDP administration in an attempt to maximize the synergy of this drug with CDDP."( Revertant and potentiating activity of lonidamine in patients with ovarian cancer previously treated with platinum.
Bottalico, C; Brandi, M; Catino, A; De Lena, M; De Mitrio, A; Gargano, G; Guida, M; Latorre, A; Leone, B; Lorusso, V; Vallejo, C, 1997)		0.3
" The amifostine peak values at the end of each 15 min infusion did not accumulate in the multiple dosing schedule."( Pharmacokinetics of amifostine and its metabolites in patients.
Eeltink, CM; Korst, AE; van der Vijgh, WJ; Vermorken, JB, 1997)		0.3
" For further studies, the recommended dosing for previously untreated patients is carboplatin 300 mg/m2 on day 1, cisplatin 70 mg/m2 on day 1, and etoposide 105 mg/m2 on days 1-3."( Combination chemotherapy with cisplatin, carboplatin, and etoposide in advanced malignancy: a phase I trial.
Camoriano, JK; Fitch, TR; Frytak, S; Rajkumar, SV; Rubin, J, 1997)		0.3
" The combination of paclitaxel 175 mg/m2 as a 3-hour infusion and carboplatin dosed to an area under the concentration-time curve of 5 is an effective therapy in patients previously treated with platinum-based chemotherapy and may be administered safely to outpatients who relapse after one or two lines of chemotherapy."( Efficacy and safety of the combination paclitaxel/carboplatin in patients with previously treated advanced ovarian carcinoma: a multicenter French Groupe des Investigateurs Nationaux pour l'Etude des Cancers Ovariens phase II study.
Curé, H; Diéras, V; Guastalla, JP; Jacquin, JP; Leduc, B; Mignot, L; Mousseau, M; Orfeuvre, H; Paraïso, D; Pujade-Lauraine, E; Tubiana-Mathieu, N; Viens, P; Vincent, P; Weber, B, 1997)		0.3
" In sequence, paclitaxel 200 mg/m2 (3-hour infusion), carboplatin dosed to an area under the concentration-time curve of 6 mg/mL x min, and methotrexate 10 mg/m2, increasing in 10-mg/m2 increments, were administered on day 1 every 21 days."( Phase I trial of paclitaxel, carboplatin, and methotrexate with granulocyte colony-stimulating factor and leucovorin in advanced transitional cell carcinoma.
Edelman, MJ; Houston, J; Lauder, I; Meyers, FJ, 1997)		0.3
" The combination of carboplatin (pharmacologically dosed at an area under the concentration-time curve of 5) and paclitaxel (135 to 175 mg/m2 over 3 hours) was given intravenously every 4 weeks for eight courses."( A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: preliminary report.
Edwards, RP; Hart, LA; Kelley, JL; Kunschner, AJ; Price, FV, 1997)		0.3
"To assess the feasibility of administering sequential cycles of dose-intensive therapy, 14 patients without prior chemotherapy for metastatic breast cancer were registered to be treated with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) at an initial dose of 250 mg/m2 over 24 hours (day 1), followed by carboplatin dosed to an area under the concentration-time curve of 16 (calculated according to the Calvert formula), every 3 weeks for four cycles."( A phase II study of repetitive cycles of dose-intense carboplatin plus paclitaxel chemotherapy and peripheral blood stem cells in metastatic breast cancer.
Adkins, D; Ford, C; Reilly, W; Spitzer, G, 1997)		0.3
" Thus IFN-gamma is cytotoxic to ovarian epithelial cells in vivo and intensive locoregional dosing over short periods is effective."( Interferon gamma induces cell cycle arrest and apoptosis in a model of ovarian cancer: enhancement of effect by batimastat.
Balkwill, FR; Burke, F; East, N; Patel, K; Upton, C, 1997)		0.3
" At this juncture, additional phase I and II trials are required to evaluate the toxicity and efficacy of topotecan in combination with other agents and address critical issues related to optimal drug dosing and sequencing."( Topotecan in combination chemotherapy.
Kaufmann, SH; Rowinsky, EK, 1997)		0.3
"In a phase II study, 66 patients with advanced breast cancer (median age 56 years; range, 28 to 75 years) were treated with paclitaxel (Taxol), 175 mg/m2 infused over 3 hours, and carboplatin (Paraplatin), dosed to attain an area under the concentration-time curve (AUC) of 6 mg x min/mL; treatment was repeated every 3 weeks."( Paclitaxel and carboplatin as first-line chemotherapy for advanced breast cancer.
Aravantinos, G; Athanassiades, A; Bafaloukos, D; Dimopoulos, MA; Fountzilas, G; Kalofonos, H; Nicolaides, C; Papadimitriou, V; Papakostas, P; Razi, E; Xiros, N, 1998)		0.3
" Full doses of both agents have been combined without any additional toxicity, and there appears to be a dose-response effect with paclitaxel."( Paclitaxel/carboplatin in the treatment of non-small-cell lung cancer.
Belani, CP, 1998)		0.3
" For each subject, one of the alternating dosing sequences (above) was repeated four times during a single dosing session which lasted approximately 40 minutes."( Intra-arterial administration of carboplatin and the blood brain barrier permeabilizing agent, RMP-7: a toxicologic evaluation in swine.
Bartus, RT; Black, KL; Gobin, YP; Kim, NN; LeBel, CP; Riley, MG; Watson, VE, 1998)		0.3
"The hematologic toxicity of arabinosylcytosine (Ara-C) and carboplatin (CBDCA) as well as the stimulating effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on murine bone marrow vary according to their dosing time along the 24-h time scale."( Circadian-based effects of AcSDKP, with or without rhG-CSF on hematologic toxicity of chemotherapy in mice.
Deschamps de Paillette, E; Filipski, E; Lévi, F; Li, XM; Soulard, C, 1998)		0.3
" IC50 values were calculated from the dose-response curves established at three cultivation time points (24, 48, and 72 h)."( Differences in the inhibition of neuritic outgrowth in organotypic cultures of rat foetal dorsal root ganglia treated with cisplatin and carboplatin: a comparative study.
Jirsová, K; Mandys, V, 1997)		0.3
" As carboplatin and cyclophosphamide cause myelosuppression which is commonly most manifest two weeks after treatment, increasing dosage intervals and reducing dosages is often necessary."( [A new therapeutic program in advanced ovarian cancer. Good results with decentralized cytostatic therapy].
Henic, E; Högberg, T, 1998)		0.3
" Dosing times of both chemotherapy and growth factor are relevant for optimization of carboplatin's hematologic tolerability."( Time dependency of hematopoietic growth factor coupled to chronotoxicity of carboplatin.
Ashkenazi, IE; Dotan, A; Peleg, L; Rienstein, S; Ron, IG; Ticher, A; Wolfson, S, 1998)		0.3
"A phase II trial was conducted to evaluate the efficacy and toxicity of the Egorin's carboplatin dosing formula with 14-day oral etoposide in 38 elderly patients with small-cell lung cancer (SCLC)."( Phase II trial of carboplatin plus oral etoposide for elderly patients with small-cell lung cancer.
Atagi, S; Fukuoka, M; Furuse, K; Hirashima, T; Kawahara, M; Kobayashi, M; Komiya, T; Kudoh, S; Masuda, N; Matsui, K; Negoro, S; Ogawara, M; Yana, T, 1998)		0.3
" Twenty patients (age range 50-79 years; inclusion criteria: WHO performance status 0-2, no previous cytotoxic treatment) with metastatic transitional cell carcinoma of the urothelium were recruited and received cytotoxic treatment with paclitaxel at a dosage of 175 mg m(-2) administered over a 3-h infusion and carboplatin given at an AUC of 5 mg ml(-1) min (according to creatinine clearance) administered every 21 days."( Paclitaxel and carboplatin in patients with metastatic urothelial cancer: results of a phase II trial.
Brodowicz, T; Grbovic, M; Marberger, M; Pflüger, H; Schnack, B; Steger, G; Wiltschke, C; Zielinski, CC, 1998)		0.3
"8, respectively, indicating a small and acceptable bias compared with that predicted from the dosing formula."( Prediction of carboplatin clearance calculated by patient characteristics or 24-hour creatinine clearance: a comparison of the performance of three formulae.
Kunikane, H; Kunitoh, H; Nagatomo, A; Okamoto, H; Watanabe, K, 1998)		0.3
" These adverse effects might be overcome by increasing the intensity of postremission therapy and modifying the dosing schedule."( Remission induction therapy of untreated acute myeloid leukemia using a non-cytarabine-containing regimen of idarubicin, etoposide, and carboplatin.
Bow, EJ; Gallant, G; Rubinger, M; Schacter, BA; Shore, TB; Williams, GJ; Woloschuk, D, 1998)		0.3
"Optimal dosage for chemotherapy administered to patients on chronic hemodialysis remains a difficult question."( [Chemotherapy of small cell bronchogenic carcinoma in a patient on hemodialysis for chronic renal failure. Apropos of a case].
Clavier, J; Daniel, C; Gouva, S; Guillodo, MP; Guillou, B; Robinet, G, 1998)		0.3
" Paclitaxel doses ranged from 135-250 mg/m2, whereas carboplatin dosing started at 250 mg/m2 and was escalated to 400 mg/m2."( A phase I trial of paclitaxel plus carboplatin in untreated patients with advanced non-small cell lung cancer.
Bunn, PA; Huffman, DH; Kelly, K; Murphy, J; Pan, Z, 1997)		0.3
" In conclusion, the application of an individualized dosing strategy is valid for the calculation of the carboplatin dose in this combination."( Evaluation of carboplatin pharmacokinetics in the absence and presence of paclitaxel.
Brennan, JM; Gallo, JM; Hamilton, TC; Johnson, SW; Kilpatrick, D; O'Dwyer, PJ; Obasaju, CK; Ozols, RF; Rogatko, A, 1996)		0.29
" Dose-response curves of melphalan, cisplatin, carboplatin, doxorubicin, and etoposide for the cell line panel were determined by measuring cytotoxicity with a 96-well-plate digital imaging microscopy (DIMSCAN) microassay."( Drug resistance patterns of human neuroblastoma cell lines derived from patients at different phases of therapy.
Groshen, S; Keshelava, N; Reynolds, CP; Seeger, RC, 1998)		0.3
" Calvert's formula has been used for carboplatin dosing and creatinine clearance applies in place of glomerular filtration rate in the formula."( Use of daily low-dose carboplatin in radiotherapy for non-small cell lung cancer.
Fuji, H; Hasegawa, S; Ishikawa, H; Kamma, H; Ohara, K; Ohtsuka, M; Satoh, H; Yamashita, YT, )		0.13
" The combination of escalating dose paclitaxel and carboplatin dosed to a fixed area under the curve (AUC) was explored in a series of phase I studies."( The clinical development of paclitaxel and the paclitaxel/carboplatin combination.
Creaven, P; Kindler, H; Meropol, N; Pendyala, L; Perez, R; Raghavan, D; Schwartz, GN, 1998)		0.3
" Carboplatin dosing was by target area under the curve (AUC) according to the Calvert protocol."( A phase I study of intravenous RMP-7 with carboplatin in patients with progression of malignant glioma.
Barton, T; Bleehen, NM; Ford, J; Osborn, C, 1998)		0.3
" A single injection of PEG-rHuMGDF ameliorates carboplatin-induced megakaryocytopenia and thrombocytopenia in a dose-response dependent fashion."( The prolonged hematologic effects of a single injection of PEG-rHuMGDF in normal and thrombocytopenic mice.
Cheung, E; del Castillo, J; Guo, J; Kaufman, S; Molineux, G; Munyakazi, L; Murphy-Filkins, R; Nelson, AG; Nichol, JL; Roskos, L; Schoemperlen, J; Senaldi, G; Sheridan, WP; Tarpley, JE; Toombs, CF; Ulich, TR; Yin, S; Young, J, 1999)		0.3
" carboplatin dosed at AUC of six infused over one hour."( Phase II trial of a paclitaxel and carboplatin combination in Asian patients with metastatic nasopharyngeal carcinoma.
Au, E; Chua, EJ; Chua, ET; Fong, KW; Khoo, KS; Khoo-Tan, HS; Lee, KM; Lee, KS; Ong, YK; Tan, EH; Tan, T; Tao, M; Wee, J; Yang, TL, 1999)		0.3
" Paclitaxel (175 mg/m2) was given as a 3-hour intravenous infusion, carboplatin was dosed to an area under the plasma concentration curve of 5 mg/m/min calculated according to the Calvert formula [(creatinine clearance + 25) x 5] as a 30-minute intravenous infusion immediately after paclitaxel."( Paclitaxel and carboplatin in patients with metastatic transitional cell cancer of the urinary tract.
Grbovic, M; Haitel, A; Heinz-Peer, G; Marberger, M; Posch, B; Pycha, A; Schnack, B; Zielinski, CC, 1999)		0.3
" Our results suggest that intracarotid infusion of etoposide can increase drug delivery of concurrent antitumor agents into tumor tissue, but cerebral parenchymal cell damage is expected with a higher dosage of etoposide."( Effect of intracarotid infusion of etoposide: modification of the permeability of the blood-brain barrier and the blood-tumor barrier in rat brain tumor model.
Furuta, T; Maeda, Y; Matsumoto, K; Mizumatsu, S; Ohmoto, T; Tamiya, T, 1999)		0.3
" Day-15 gemcitabine dosing is problematic and may contribute to excessive thrombocytopenia when gemcitabine is combined with carboplatin."( Gemcitabine and carboplatin in combination: an update of phase I and phase II studies in non-small cell lung cancer.
Calvert, P; Edelman, MJ; Gandara, DR; Langer, CJ; Ozols, RF, 1999)		0.3
" The findings indicate that a method is available to rationally address the design of dosing schedules in concurrent therapy regimens."( Alterations of intratumoral pharmacokinetics of 5-fluorouracil in head and neck carcinoma during simultaneous radiochemotherapy.
Bachert, P; Becker, M; Dietz, A; Knopp, MV; Rudat, V; Schlemmer, HP; van Kaick, G; Vanselow, B; Wannenmacher, M; Weidauer, H; Wollensack, P; Zuna, I, 1999)		0.3
" The optimal dosing regimen with amifostine and carboplatin needs to be further evaluated in clinical studies."( Approaches to managing carboplatin-induced thrombocytopenia: focus on the role of amifostine.
Budd, GT; Bukowski, RM; Ganapathi, R; McLain, D; Snyder, J; Wood, L, 1999)		0.3
" The objectives of this study were to validate the carboplatin dosing formula during high dose intensity therapy and evaluate the relationship between systemic carboplatin exposure and Pt-DNA adduct levels in peripheral blood leucocytes."( Pharmacokinetically guided dose escalation of carboplatin in epithelial ovarian cancer: effect on drug-plasma AUC and peripheral blood drug-DNA adduct levels.
Baily, N; Calvert, AH; Ghazal-Aswad, S; Lind, M; Newell, DR; Sinha, DP; Tilby, MJ, 1999)		0.3
"Pharmacokinetically-based carboplatin dosing during high intensity therapy accurately predicted the dose required to achieve a target AUC and resulted in consistent patient exposure to active drug."( Pharmacokinetically guided dose escalation of carboplatin in epithelial ovarian cancer: effect on drug-plasma AUC and peripheral blood drug-DNA adduct levels.
Baily, N; Calvert, AH; Ghazal-Aswad, S; Lind, M; Newell, DR; Sinha, DP; Tilby, MJ, 1999)		0.3
" Collectively, these data provide the first systematic evaluation of dosing parameters involving receptor-mediated changes in BBTB permeability and provide new information regarding the pharmacodynamics and potential clinical use of Cereport."( Enhanced delivery of carboplatin into brain tumours with intravenous Cereport (RMP-7): dramatic differences and insight gained from dosing parameters.
Agostino, M; Bartus, RT; Dean, R; Emerich, DF; Hasler, B; Kim, BS; Pink, M; Snodgrass, P; Xiong, H, 1999)		0.3
" Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1)."( Epoetin alpha prevents anaemia and reduces transfusion requirements in patients undergoing primarily platinum-based chemotherapy for small cell lung cancer.
Bell, DR; De Campos, ES; Ewers, SB; Morant, R; Rosso, R; Schatzmann, E; Steward, WP; Stocker, H; Sundal, E; Thatcher, N; Vansteenkiste, JF; Varghese, G, 1999)		0.3
" There has been a tendency to a dose-response relationship for the combination with only six partial responses (27%) reported in 22 patients who received paclitaxel at doses < or = 195 mg/m2 and carboplatin at doses < 350 mg/m2 and 12 partial responses in 25 patients (48%) receiving paclitaxel > 195 mg/m2 and carboplatin > or = 350 mg/m2, respectively."( Phase I/II dose finding study of paclitaxel and carboplatin in advanced non-small cell lung cancer.
Corgna, E; Crinó, L; Gentile, A; Marracolo, F; Novello, S; Palladino, M; Pozzi, E; Salsano, G; Scagliotti, GV; Selvaggi, G; Tonato, M, 1999)		0.3
" infusion via an ambulatory infusion pump with patient-activated intermittent dosing (BAD pump) for prevention of acute and delayed nausea/vomiting in patients receiving high-dose chemotherapy (HDC) for peripheral blood progenitor cell (PBPC) mobilization (MOB) or prior to autologous PBPC rescue."( Safety and efficacy of a continuous infusion, patient controlled anti-emetic pump to facilitate outpatient administration of high-dose chemotherapy.
Belt, R; Coon, J; Cord, M; Dix, S; Geller, R; Howard, S, 1999)		0.3
"The target area under the plasma-concentration-versus-time curve (AUC)-based dosing of carboplatin using Calvert's formula is expected to result in more acceptable toxicity and greater efficacy in elderly patients with small-cell lung cancer (SCLC) than the body surface area-based dosing strategy."( Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer.
Hayashi, I; Isobe, H; Kurita, Y; Masutani, M; Mori, K; Nakata, K; Nishiwaki, Y; Okamoto, H; Saijo, N; Tsuchiya, S; Watanabe, K, 1999)		0.3
" IC50 values were obtained from dose-response curves after fitting the data to the linear quadratic equation."( Carboplatin-paclitaxel- and carboplatin-docetaxel-induced cytotoxic effect in epithelial ovarian carcinoma in vitro.
Engblom, P; Grènman, S; Kulmala, J; Rantanen, V, 1999)		0.3
" AUC dosing of carboplatin was equivalent for both groups."( Is age a barrier to the aggressive treatment of ovarian cancer with paclitaxel and carboplatin?
Gardner, J; Hall, JB; Higgins, RV; Naumann, RW, 1999)		0.3
"The frequent use of platinum (Pt) complexes in cancer chemotherapy and the application of new therapeutic options and dosing strategies have increased the need for rapid analytic procedures to determine Pt concentrations in the biologic fluids of patients."( Determination of platinum complexes in clinical samples by a rapid flameless atomic absorption spectrometry assay.
Appelius, H; Jaehde, U; Kloft, C; Schunack, W; Siegert, W, 1999)		0.3
" We conclude that CBP at a cumulative dosage of 1 g/m2 together with intercalating agents (IDA/MIT) has antileukemic efficacy in elderly patients."( Continuous-infusion carboplatin in combination with idarubicin or mitoxantrone for high-risk acute myeloid leukemia: a randomised phase II study.
Archimbaud, E; Assouline, D; Belhabri, A; Blanc, M; Fière, D; Michallet, M; Thomas, X; Tigaud, JD; Troncy, J; Wattel, E, 1999)		0.3
" Carboplatin dosage was calculated individually to achieve a target systemic free carboplatin exposure."( Platinum distribution in malignant glioma following intraoperative intravenous infusion of carboplatin.
Jodrell, DI; Malcolm, G; Reid, M; Whittle, IR, 1999)		0.3
" Neurological impairment, performance status and steroid use were measured prior to dosing at each cycle and tumour volume by 3-D MRI at the end of cycles 2, 4, 6, 9 and 12."( Phase II studies of RMP-7 and carboplatin in the treatment of recurrent high grade glioma. RMP-7 European Study Group.
Barton, T; Grant, R; Gregor, A; Hadley, DM; Lind, M; Newman, H; Osborn, C, 1999)		0.3
" The present retrospective analysis assessed two ways of dosing carboplatin: according to body surface area (mg/m2) or to the estimated targeted area under the concentration versus time curve (AUC)."( A comparison of methods of calculation for estimating carboplatin AUC with a retrospective pharmacokinetic-pharmacodynamic analysis in patients with advanced non-small cell lung cancer. European Lung Cancer Working Party.
Alexopoulos, CG; Berchier, MC; Bureau, G; Giner, V; Klastersky, J; Koumakis, G; Lafitte, JJ; Lecomte, J; Mommen, P; Ninane, V; Paesmans, M; Sculier, JP; Thiriaux, J; Zacharias, C, 1999)		0.3
" The AUC of carboplatin measured in serum was lower than the target AUC; this may be related to underestimation of the glomerular filtration rate used in the dosing formula."( Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients.
Bains, M; Bajorin, DF; Bosl, GJ; Flombaum, C; Macapinlac, HA; Mariani, T; Mazumdar, M; Motzer, RJ; Reich, L; Sheinfeld, J; Tong, WP, 2000)		0.31
" Optimal dosing of carboplatin in the high-dose setting warrants further investigation."( Sequential dose-intensive paclitaxel, ifosfamide, carboplatin, and etoposide salvage therapy for germ cell tumor patients.
Bains, M; Bajorin, DF; Bosl, GJ; Flombaum, C; Macapinlac, HA; Mariani, T; Mazumdar, M; Motzer, RJ; Reich, L; Sheinfeld, J; Tong, WP, 2000)		0.31
"In the Phase I portion, paclitaxel 200 mg/m(2) (3-hour infusion), carboplatin dosed to an area under the curve (AUC) of 6 mg/mL."( Phase I/II study of paclitaxel, carboplatin, and methotrexate in advanced transitional cell carcinoma: a well-tolerated regimen with activity independent of p53 mutation.
deVere White, RW; Edelman, MJ; Gandour-Edwards, R; Meyers, FJ; Miller, TR; Williams, SG, 2000)		0.31
" Based on the reported activity of 1-h paclitaxel infusion in NSCLC and minimal myelosuppression at doses of 135 and 200 mg/m2 every 3 weeks and the suggestion of a dose-response relationship, we launched an intrapatient dose escalation trial of combination carboplatin and 1-h paclitaxel."( Paclitaxel by 1-h infusion in combination with carboplatin in advanced non-small cell lung carcinoma (NSCLC).
Alexander, R; Blankstein, K; Bonjo, CA; Kosierowski, R; Langer, CJ; Litwin, S; McAleer, CA; Millenson, M; Ozols, RF, 2000)		0.31
" Dosage adjustments were performed according to daily controls of their AUC in order to obtain a total AUC of 20 mg/ml x min."( A limited sampling strategy for determining carboplatin AUC and monitoring drug dosage.
Canal, P; Chatelut, E; Chevreau, C; Milano, G; Otto, J; Pivot, X; Renée, N; Thyss, A, 2000)		0.31
" A number of different dosing schedules are being investigated in clinical trials including oral administration, a daily infusion on 5- or 3-consecutive days and a continuous infusion for 21 days."( [Topotecan: prospects for using it in combination therapy for ovarian carcinoma].
Scarfone, G, )		0.13
" In the second and third courses of the chemotherapy, CBDCA and TXT were administered in the same dosage as in the initial course, but with the oral administration of UFT (600 mg/day)."( [A case of epithelial cancer of the alveoli which responded favorably to the additional administration of UFT for refractory cancer after administration of carboplatin and docetaxel].
Kuwahara, M; Motohiro, A; Takahashi, N; Tsukamoto, S; Ueda, H, 2000)		0.31
" The Bayesian method may be very instrumental to execute pharmacokinetic guided dosing for carboplatin."( Validation of techniques for the prediction of carboplatin exposure: application of Bayesian methods.
Beijnen, JH; Huitema, AD; Mathôt, RA; Rodenhuis, S; Schellens, JH; Tibben, MM, 2000)		0.31
" The carboplatin AUC dosing level was 4, 5, or 6 in 6, 5, and 16 individuals, respectively."( The antiemetic efficacy of oral ondansetron plus intravenous dexamethasone in patients with gynecologic malignancies receiving carboplatin-based chemotherapy.
Belinson, J; Kennedy, A; Kulp, B; Markman, M; Peterson, G; Webster, K, 2000)		0.31
"In this multicenter, phase II trial, 33 patients with previously untreated stage IIIB (n = 8) or IV (n = 25) NSCLC received intravenous infusions of docetaxel 80 mg/m2 followed immediately by carboplatin dosed to AUC of 6 mg/ml/min (Calvert's formula) every three weeks."( Multicenter phase II trial of docetaxel and carboplatin in patients with stage IIIB and IV non-small-cell lung cancer.
Belani, CP; Bonomi, P; Capozzoli, MJ; Cohen, LJ; Dobbs, T; Earhart, R; Einzig, A; Luketich, JD, 2000)		0.31
" This article describes recent clinical trials evaluating gemcitabine plus carboplatin, and the impact of the dosing schedule on the feasibility and tolerability of this combination."( Gemcitabine/carboplatin combination regimens: importance of dose schedule.
Edelman, MJ; Gandara, DR; Lara, PN; Lau, DH, 2000)		0.31
" The study design was based on the hypothesis that the non-overlapping toxicities of a 3-drug combination of irinotecan (Camptosar, CPT-11), carboplatin (Paraplatin), and paclitaxel (Taxol) would allow them to be dosed at recommended or standard doses, respectively."( Phase I/II trial of irinotecan, carboplatin, and paclitaxel in advanced or metastatic NSCLC.
Israel, VP; Miller, L; Natale, RB; Sandler, A; Socinski, M, 2000)		0.31
" The ongoing phase II portion of the study is restricted to previously untreated patients who will receive at least one cycle of either cisplatin or carboplatin in combination with etoposide followed by irinotecan at 60 mg/m2 and paclitaxel at 50 mg/m2 dosed once weekly for 3 weeks."( Phase I/II study of weekly irinotecan and paclitaxel in patients with SCLC.
Rushing, DA, 2000)		0.31
" Ninety nine patients (group A) were randomized to receive paclitaxel 175 mg/m2 in three-hour infusion plus carboplatin dosed to an area under the concentration-time curve of 6 every 3 weeks and 99 (group B) to receive the same regimen with paclitaxel increased to 225 mg/m2."( Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versus paclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): a multicenter randomized trial. Hellenic Cooperative Oncology Group (HeCOG).
Dimopoulos, M; Fountzilas, G; Kalophonos, C; Kosmidis, P; Mylonakis, N; Nikolaidis, C; Papaconstantinou, C; Papadimitriou, C; Pavlidis, N; Samantas, E; Skarlos, D, 2000)		0.31
" Based on previous animal experimentation and clinical experience with other hematopoietic cytokines, we found that daily dosing with TPO augmented the recovery of both the megakaryocyte and erythroid lineages in a mouse model of pancytopenia."( In vivo biological effects of various forms of thrombopoietin in a murine model of transient pancytopenia.
Eaton, DL; Errett, CJ; Marian, M; Mathias, J; Meng, G; Thibodeaux, H; Thomas, GR; Vandlen, RL, 1996)		0.29
" Our trial failed to demonstrate a significant improvement in response or survival when patients with metastatic NSCLC were treated, in addition to ifosfamide and mitomycin, by combination of moderate dosages of cisplatin and carboplatin instead of moderate dosage of cisplatin alone."( Phase III randomized trial comparing moderate-dose cisplatin to combined cisplatin and carboplatin in addition to mitomycin and ifosfamide in patients with stage IV non-small-cell lung cancer.
Alexopoulos, CG; Baumöhl, J; Berghmans, T; Florin, MC; Klastersky, J; Koumakis, G; Lafitte, JJ; Mommen, P; Ninane, V; Paesmans, M; Schmerber, J; Sculier, JP; Thiriaux, J; Zacharias, C, 2000)		0.31
" The maximum tolerated dosage of weekly paclitaxel during standard continuous-course XRT is confirmed to be 30 mg/m2/week."( Pilot study of organ preservation multimodality therapy for locally advanced resectable oropharyngeal carcinoma.
Algazy, KM; Aviles, VM; Chalian, AA; Greenberg, MJ; Hershock, D; Machtay, M; Mirza, N; Neubauer, R; Rosenthal, DI; Weber, RS; Weinstein, GS, 2000)		0.31
"Carboplatin dosing in adults with cancer is based on renal function."( Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial.
Boddy, AV; English, MW; Hobson, R; Imeson, J; Lewis, I; Morland, B; Newell, DR; Pearson, AD; Pinkerton, R; Price, L; Stevens, M; Thomas, H, 2000)		0.31
"Thirty-eight pediatric patients were randomized to receive a carboplatin dose calculated according to surface area or a renal function-based dosing formula."( Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial.
Boddy, AV; English, MW; Hobson, R; Imeson, J; Lewis, I; Morland, B; Newell, DR; Pearson, AD; Pinkerton, R; Price, L; Stevens, M; Thomas, H, 2000)		0.31
"The mean observed areas under the carboplatin concentration-versus-time curve (AUCs) after renal function- and surface area-based dosing were 98% and 95% of the target AUCs, respectively."( Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial.
Boddy, AV; English, MW; Hobson, R; Imeson, J; Lewis, I; Morland, B; Newell, DR; Pearson, AD; Pinkerton, R; Price, L; Stevens, M; Thomas, H, 2000)		0.31
"Renal function-based carboplatin dosing in children results in more consistent drug exposure than surface area-based drug administration."( Prospective validation of renal function-based carboplatin dosing in children with cancer: A United Kingdom Children's Cancer Study Group Trial.
Boddy, AV; English, MW; Hobson, R; Imeson, J; Lewis, I; Morland, B; Newell, DR; Pearson, AD; Pinkerton, R; Price, L; Stevens, M; Thomas, H, 2000)		0.31
" Several methods of dosage individualisation a priori (before carboplatin administration) have been proposed."( [Pharmacokinetics and individual dose adjustment of carboplatin].
Bugat, R; Canal, P; Chatelut, E, 2000)		0.31
" Prospective studies of pharmacokinetically guided versus surface area-based administration should be performed to validate pharmacokinetic-pharmacodynamic relationships and to facilitate optimal dosage of anticancer agents in the clinic."( Pharmacokinetically guided administration of chemotherapeutic agents.
Beijnen, JH; Mathôt, RA; Schellens, JH; van den Bongard, HJ, 2000)		0.31
" At the same time the carboplatin dosing calculation was changed and an area under the curve (AUC) formula rather than by mg/m2 was used to calculate this."( Should high-dose chemotherapy be used to consolidate second or third line treatment in relapsing germ cell tumours?
Gallagher, CJ; Gupta, RK; Kelsey, S; Lister, TA; Newland, AC; O'Doherty, CA; Oliver, RT; Shamash, J, 2000)		0.31
"The carboplatin-mitoxantrone combination, at the dosage tested in this study, appears to be well tolerated by elderly patients with advanced ovarian cancer and is associated with an acceptable response rate."( Elderly ovarian cancer: treatment with mitoxantrone-carboplatin.
Amichetti, M; Artioli, G; Azzoni, P; Donach, M; Endrizzi, L; Ferrazzi, E; Monfardini, S; Nicoletto, MO; Prosperi, A; Salvagno, L; Sileni, VC; Talamini, R; Tumolo, S; Veronesi, A; Visonà, E, 2001)		0.31
" We wanted to show that the safety and efficacy of the drug could be improved by pharmacologically-guided dosing based on renal function."( Combined modality treatment using concurrent radiotherapy and pharmacologically-guided carboplatin for inoperable and incompletely resected non-small cell lung cancer.
Ball, D; Fisher, R; Grossi, M; Mac Manus, M; Millward, M; Porceddu, S; Ryan, G; Wirth, A, 2001)		0.31
"Radical chest irradiation can be combined with two cycles of pharmacologically-guided full-dose carboplatin, however because our study demonstrated significant haematologic toxicity, we recommend carboplatin dosing according to renal function at less than full dose (i."( Combined modality treatment using concurrent radiotherapy and pharmacologically-guided carboplatin for inoperable and incompletely resected non-small cell lung cancer.
Ball, D; Fisher, R; Grossi, M; Mac Manus, M; Millward, M; Porceddu, S; Ryan, G; Wirth, A, 2001)		0.31
" Combined dosing of NDP with GEM resulted in synergistically enhanced inhibition of tumor growth in the Ma44 tumor model."( Preclinical in vivo antitumor efficacy of nedaplatin with gemcitabine against human lung cancer.
Hojo, K; Maekawa, R; Maki, H; Matsumoto, M; Nishitani, Y; Takeda, Y; Wada, T; Yoshioka, T, 2001)		0.31
"These data stress the importance of dosing carboplatin according to renal function and age and warrant further analyses to validate this concept prospectively."( Carboplatin pharmacokinetics in patients receiving carboplatin and paclitaxel/docetaxel for advanced lung cancers: impact of age and renal function on area under the curve.
Braess, J; Friedrichsen, S; Hiddemann, W; Kaufmann, CC; Kern, W; Schleyer, E, 2001)		0.31
" The formulae developed here can be used to provide reliable estimates of GFR, particularly in regard to targeted dosing of carboplatin."( Estimation of glomerular filtration rate in cancer patients.
Boddy, AV; Calvert, AH; Fenwick, J; Highley, M; McGill, A; Wright, JG, 2001)		0.31
" The dosage of TXL was 150 to 180 mg/m2."( [Dose finding study of paclitaxel and carboplatin for ovarian cancer (JKTB)].
Aoki, D; Kikuchi, Y; Kimura, E; Kita, T; Nishida, M; Nozawa, S; Ochiai, K; Tada, S; Tsunoda, H; Udagawa, Y; Yasuda, M, 2001)		0.31
"Carboplatin is frequently dosed to achieve a desired area under the plasma concentration-time curve (AUC) by using the Calvert or Chatelut equations to estimate carboplatin clearance."( Measured versus estimated glomerular filtration rate in the Calvert equation: influence on carboplatin dosing.
Donahue, A; Faucette, S; Gillenwater, HH; Kowalski, RJ; Lindley, C; McCune, JS; Socinski, MA, 2001)		0.31
" It is not clear however, as to why dosing by BSA was extended to the routine dosing of antineoplastic agents."( Body surface area as a determinant of pharmacokinetics and drug dosing.
Ratain, MJ; Sawyer, M, 2001)		0.31
" The carboplatin dosage was escalated from an AUC of 4 to 5 to 6 (Calvert formula)."( Phase I and pharmacologic study of sequential topotecan, carboplatin, and etoposide.
Miller, AA; Niell, HB, )		0.13
" Cumulative dose-response plots of primary breast cancer tumor cells responding in vitro with > or = 90% growth inhibition showed a strong dose dependence for both EPI/PTX and CBDCA/PTX."( Drug interactions and cytotoxic effects of paclitaxel in combination with carboplatin, epirubicin, gemcitabine or vinorelbine in breast cancer cell lines and tumor samples.
Beryt, M; Felber, M; Hepp, H; Kahlert, S; Konecny, G; Langer, E; Lude, S; Pegram, M; Slamon, D; Untch, M, 2001)		0.31
" All reactors had low-grade gliomas treated with weekly CBDCA and vincristine, with a dosage per treatment <500 mg/m2."( Weekly dosing of carboplatin increases risk of allergy in children.
Dahl, GV; Fisher, PG; Shames, RS; Yu, DY, )		0.13
" The repetitive, weekly dosing schedule of CBDCA appears to be a key risk factor for allergic reaction in brain tumor patients."( Weekly dosing of carboplatin increases risk of allergy in children.
Dahl, GV; Fisher, PG; Shames, RS; Yu, DY, )		0.13
" For the three of them, plasma clearance is correlated to creatinine clearance, but only carboplatin dosage can be individually adjusted, based on creatinine clearance measurement, thanks to its simple renal excretion, due to exclusive glomerular filtration, and after Calvert's, Egorin's and Chatelut's population kinetics studies."( [Pharmacokinetic properties of platinium derivatives].
Allain, P; Boisdron-Celle, M; Gamelin, E; Lebouil, A, 2001)		0.31
" In contrast, the sequential dosing of TXL prior to NDP (TN therapy) resulted in synergistically enhanced inhibition of tumor growth with less toxicity compared with the NT therapy."( Sequence-dependent antitumor efficacy of combination chemotherapy with nedaplatin, a newly developed platinum, and paclitaxel.
Maekawa, R; Uchida, N; Yamada, H; Yoshioka, T, 2001)		0.31
"The purpose of this study was to define the maximum tolerated dose (MTD) of topotecan given as escalating doses combined to a fixed dosage of carboplatin in late relapsing ovarian carcinomas."( A phase I/II study of topotecan in combination with carboplatin in recurrent epithelial ovarian cancer.
Bolis, G; Guarnerio, P; Parazzini, F; Polverino, GP; Rosa, C; Scarfone, G; Sciatta, C, 2001)		0.31
" In forty patients, carboplatin dosing was performed according to the Chatelut formula where the serum creatinine level was corrected according to the above equation."( Impact of the biochemical assay for serum creatinine measurement on the individual carboplatin dosing: a prospective study.
Canal, P; Chatelut, E; Delord, JP; Léger, F; Lochon, I; Makdessi, J; Sarda, C; Séronie-Vivien, S, 2002)		0.31
" The same drugs and dosage were used in the two groups."( [A comparative clinical study of carboplatin solution and carboplatin powder].
Li, Q; Qu, F; Zhou, J, 2001)		0.31
"These results indicate that AUC-based dosing of carboplatin is still rational in combination chemotherapy."( Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer.
Ando, M; Ando, Y; Hasegawa, Y; Ikeda, T; Minami, H; Saka, H; Sakai, S; Sato, M; Sekido, Y; Shimokata, K; Watanabe, A; Yamamoto, M, 2001)		0.31
" Dosing of carboplatin based on the AUC produced an acceptable degree of thrombocytopenia and neutropenia."( Paclitaxel and carboplatin combination chemotherapy in a hemodialysis patient with advanced ovarian cancer.
Aoki, Y; Kase, H; Kato, N; Kikuchi, M; Sato, T; Takaki, Y; Tanaka, K; Tomita, M; Watanabe, M, 2002)		0.31
" Forty-nine had received prior cisplatin (median cumulative dosage 450 mg/m2); the others had received prior treatment with carboplatin."( Retreatment with dose-dense weekly cisplatin after previous cisplatin chemotherapy is not complicated by significant neuro-toxicity.
de Wit, R; Hilkens, PH; van den Bent, MJ; van der Burg, ME; van Putten, WL, 2002)		0.31
" Although chemotherapy is useful, further study is needed for the selection of suitable chemotherapeutic regimens, optimal dosage of each drug and the timing of HD."( [Chemotherapy for small-cell lung cancer (SCLC) patients with renal failure].
Fushimi, H; Nakajima, S; Obana, T; Okuda, K; Takenaka, M; Tanio, Y; Tsubakihara, Y; Watanabe, D; Yanagita, M, 2002)		0.31
"Pharmacokinetic analysis of carboplatin dosing suggests a more accurate prediction of toxicity when the dose is based on the area under the plasma concentration vs time curve (AUC) instead of body surface area (BSA)."( High-dose carboplatin and regimen-related toxicity following autologous bone marrow transplant.
Colby, C; Koziol, S; McAfee, SL; Spitzer, TR; Yeap, B, 2002)		0.31
" As a result, both the host tolerance and antitumor efficacy of 5-fluorouracil (5-FU) and oxaliplatin (L-OHP), like 30 other anticancer drugs, vary largely according to the dosing time in laboratory rodents."( Chronotherapy of colorectal cancer.
Giacchetti, S, 2002)		0.31
" Further detailed pharmacokinetic studies of irinotecan in patients receiving concomitant therapy with enzyme-inducing anticonvulsants are required so that rational dosing recommendations can be provided for this patient population."( Influence of phenytoin on the disposition of irinotecan: a case report.
Berg, S; Bernstein, M; Blaney, SM; Cherrick, I; Kuttesch, N; Murry, DJ; Salama, V, 2002)		0.31
" Some courses were given at a reduced dose or delayed due to toxicity but these dosage modifications were thought to be acceptable for both TXL and CBDCA."( [Phase II study of combination therapy with paclitaxel and carboplatin against postoperative small residual disease in patients with stage I c-IV ovarian cancer--KCOG 989 trial].
Adachi, S; Fujita, H; Hara, Y; Hiraoka, K; Honjo, H; Hosokawa, K; Itani, Y; Itoh, K; Itoh, R; Kimura, T; Koishi, K; Koshiba, H; Nakata, Y; Toyoda, S; Tsuchiya, H; Yamada, T; Yamagami, K, 2002)		0.31
" First, an inverted U dose-response was observed, wherein further dose escalation beyond the optimal dose was not efficacious and indeed produced significant local toxicity."( Injection of chemotherapeutic microspheres and glioma. III: Parameters to optimize efficacy.
Bartus, RT; Emerich, DF; Winn, SR, 2002)		0.31
" In the second stage, which begins at the first instance of DLT, a two-parameter logistic dose-response model estimates the MTD from the DLT experience of all patients."( Adaptive dose finding for phase I clinical trials of drugs used for chemotherapy of cancer.
Potter, DM, 2002)		0.31
" In stage 4 patients, there was an additional effect of high dosed carboplatin."( The incidence of hearing impairment after successful treatment of neuroblastoma.
Berthold, F; Dupuis, W; Hero, B; Selle, B; Simon, T, )		0.13
" Further, the paclitaxel dosage and paclitaxel AUC were also dose-dependent."( Clinical trial and pharmacokinetic study of combination paclitaxel and carboplatin in patients with epithelial ovarian cancer.
Fujimoto, S; Hirano, T; Kaneuchi, M; Negishi, H; Nishiya, M; Okamoto, K; Sakuragi, N; Takeda, M; Todo, Y; Yamamoto, R, 2002)		0.31
" In addition, single-sample and two-sample limited sampling models (LSMs) were derived to estimate carboplatin's AUC that could be used in the design of drug dosing regimens."( Population pharmacokinetic and limited sampling models for carboplatin administered in high-dose combination regimens with peripheral blood stem cell support.
Gallo, JM; Obasaju, C; Schilder, RJ; Shen, M, 2002)		0.31
" It is concluded that cyclophosphamide and thiotepa in obese patients should not be dosed on the basis of BSA incorporating TBW since the patient will be overexposed."( Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin.
Beijnen, JH; De Jonge, ME; Mathôt, RA; Rodenhuis, S; Van Dam, SM, 2002)		0.31
" The maximum tolerated dosage included 205 mg/m(2) paclitaxel."( Phase I/II trial of accutane as a potentiator of carboplatin and paclitaxel in squamous cell carcinomas.
Baredes, S; Bryan, M; Hameed, M; Korah, R; Pavlick, AC; Pliner, L; Saunders, T; Wieder, R, 2002)		0.31
" Carboplatin dosed to an area under the time-concentration curve (AUC) of 6 mg/ml."( A multicenter phase II study of docetaxel and carboplatin combination as front-line treatment in advanced non-small cell lung cancer.
Agelaki, S; Georgoulias, V; Giannakakis, T; Kakolyris, S; Kalbakis, K; Kouroussis, C; Michailakis, E; Papadouris, S; Souglakos, J; Theodoropoulos, E; Tsitoura, M; Vardakis, N, )		0.13
" Compared with the cell necrosis, the dosage of drugs was less and the time was shorter for inducing apoptosis."( [Apoptosis of human pancreatic carcinoma cell lines induced by combinations of chemotherapeutic drugs].
Cai, L; Liao, Q; Wu, Y; Zhao, Y; Zhu, Y, 1999)		0.3
"Using AUC-based dosing compensates for variations in renal function between and within individual patients."( Carboplatin dosing accounting for the renal and hematologic status of patients.
Busse, T, )		0.13
" These results suggest that optimal dosage for targeting a given AUC may vary within a 13-fold range between patients."( Pharmacokinetics of low-dose carboplatin and applicability of a method of calculation for estimating individual drug clearance.
Bensadoun, RJ; Canal, P; Chatelut, E; Etienne, MC; Guardiola, E; Leger, F; Magné, N; Milano, G; Pivot, X; Renée, N, 2003)		0.32
" Dose-limiting toxicities were thrombocytopenia and liver failure, and with repeated dosing neutropenia was commonly observed."( Phase I trial of fixed dose-rate gemcitabine in combination with carboplatin in chemonaive advanced non-small-cell lung cancer: a Cancer Therapeutics Research Group study.
Goh, BC; Lee, HS; Lee, SC; Lehnert, M; Lim, HL; Millward, MJ; Soo, RA; Tok, LT; Wang, LZ, 2003)		0.32
" EDX dosage was chosen after a pilot phase I study."( First-line chemotherapy with epidoxorubicin, paclitaxel, and carboplatin for the treatment of advanced epithelial ovarian cancer patients.
Carnino, F; Conte, PF; Cosio, S; Fanucchi, A; Gadducci, A; Lionetto, R; Pastorino, S; Romanini, A; Tanganelli, L, 2003)		0.32
"A phase I study of carboplatin (Paraplatin) administered in two different dosing schedules (single dose every 4 weeks and weekly dosing) in combination with weekly irinotecan (CPT-11, Camptosar) was conducted in patients with relapsed or refractory advanced malignancies."( Phase I. Trial of irinotecan plus carboplatin in two dose schedules.
Burris, HA; Greco, FA; Hainsworth, JD; Jones, SF; Kuzur, ME; Miranda, FT; Raefsky, EA; White, MB; Willcutt, NT; Yardley, DA, 2003)		0.32
"Individual dosing of carboplatin based on drug monitoring was performed within a multi-centric phase I study based on high AUC-levels in children."( Individual dosing of carboplatin based on drug monitoring in children receiving high-dose chemotherapy.
Barberi-Heyob, M; Bastian, G; Catalin, J; Chastagner, P; Chatelut, E; Doz, F; Drouard-Troalen, L; Gentet, JC; Rubie, H; Urien, S; Vassal, G, 2003)		0.32
" Paclitaxel 175 mg/m2 was given as a 3-hour intravenous infusion, and carboplatin was dosed to the area under the plasma concentration-time curve (AUC) of 5 mg."( [Pharmacokinetics of paclitaxel and carboplatin in a hemodialysis patient with metastatic urothelial carcinoma--a case report].
Araki, I; Furuya, Y; Takeda, M; Takihana, Y; Tanabe, N, 2003)		0.32
" Among the newer agents available for the experimental treatment arms, three stood out-gemcitabine, polyethylene-glycol (PEG)-liposomal doxorubicin, and topotecan-based on evidence of their activity demonstrated in previous phase I and II trials and, with appropriate dosage modifications, manageable toxicity when used in combination with platinum."( Clinical trials of newer regimens for treating ovarian cancer: the rationale for Gynecologic Oncology Group Protocol GOG 182-ICON5.
Bookman, M; Copeland, LJ; Trimble, E, 2003)		0.32
" The exact dosing and different mechanism of action of gemcitabine make it attractive for these combinations."( Gemcitabine combination chemotherapy of ovarian cancer.
Mutch, DG, 2003)		0.32
"In contrast to conventional chemotherapy, carboplatin is still dosed per unit of body surface area (BSA) in high-dose chemotherapy protocols in clinical practice."( Individualised dosing strategy for high-dose carboplatin in patients with germ cell cancer.
Jaehde, U; Kloft, C; Siegert, W, 2003)		0.32
" It was decided, in the context of a recent clinical trial comparing two dosing schedules of paclitaxel and carboplatin for advanced stage IIIB/IV non-small-cell lung cancer, that the randomized block procedure could not simultaneously protect sufficiently against both selection and chronological bias."( Minimizing predictability while retaining balance through the use of less restrictive randomization procedures.
Berger, VW; Ivanova, A; Knoll, MD, 2003)		0.32
" Topotecan tolerability and convenience may be improved by employing a lower dose, shorter schedule, 21-day continuous infusion or weekly dosing in relapsed/refractory disease."( Workshop: options for therapy in ovarian cancer.
Herzog, TJ; Holloway, RW; Stuart, GC, 2003)		0.32
"Carboplatin is currently recommended to be dosed according to renal function."( Misinterpretation of a Calvert-derived formula leading to carboplatin overdose in two children.
Arceci, RJ; Chen, AR; Higman, MA; Liem, RI, 2003)		0.32
" For first-line chemotherapy, most investigators recommended treatment with etoposide/cisplatin, with possible dosing variations according to tolerability and convenience."( Options for first- and second-line therapy in small cell lung cancer--a workshop discussion.
Eckardt, J; Green, M; Thatcher, N, 2003)		0.32
"Six-month intravenous chemotherapy included carboplatin plus etoposide alternating with cyclophosphamide plus vincristine (Regimen 1) and the same drugs at higher dosage plus idarubicin (Regimen 2)."( Results of a prospective study for the treatment of retinoblastoma.
Casak, S; Chantada, G; Dávila, MT; Fandiño, A; Manzitti, J; Raslawski, E; Schvartzman, E, 2004)		0.32
" For each tumor-derived cell culture, a complete dose-response curve was established for each chemotherapeutic agent tested."( Metastatic lung disease to the central nervous system: in vitro response to chemotherapeutic agents.
Burholt, DR; Donovan, M; George, LD; Kornblith, PL; Marsh, JW, 2004)		0.32
"The results indicate that the applied pharmacokinetically guided dosing strategy for paclitaxel is safe and technically feasible."( Bayesian pharmacokinetically guided dosing of paclitaxel in patients with non-small cell lung cancer.
Baas, P; Beijnen, JH; de Jonge, ME; Huitema, AD; Mathôt, RA; Rosing, H; Schellens, JH; van den Bongard, HJ; van Zandwijk, N, 2004)		0.32
" Yet, benefits of higher radiation dosage need evaluation."( Clinical issues in the management of non-small-cell lung cancer and the role of platinum-based therapy.
Socinski, MA, 2004)		0.32
"An approach to carboplatin dosing in children with bilateral nephrectomy using a renal function-based dosing formula with a glomerular filtration rate of zero was investigated in the current study."( Pharmacokinetically guided dosing of carboplatin in paediatric cancer patients with bilateral nephrectomy.
Boddy, AV; Cole, S; English, MW; Glaser, A; Grundy, RG; Holden, V; Howe, K; Michalski, A; O'Meara, A; Shakespeare, C; Veal, GJ; Waters, F, 2004)		0.32
"To determine the pharmacokinetics of adaptively dosed carboplatin when administered in combination with the bradykinin agonist, lobradimil (RMP-7, Cereport), to pediatric patients with brain tumors."( Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors.
Aikin, A; Balis, FM; Egorin, M; Gervais, A; Warren, K, 2004)		0.32
" The adaptive dosing formula was: carboplatin dose (mg/m2)=target AUC (mg."( Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors.
Aikin, A; Balis, FM; Egorin, M; Gervais, A; Warren, K, 2004)		0.32
"Adaptive dosing of carboplatin based on GFR overestimated the dose required to achieve the target carboplatin AUC in pediatric patients with brain tumors treated with concurrent lobradimil."( Pharmacokinetics of carboplatin administered with lobradimil to pediatric patients with brain tumors.
Aikin, A; Balis, FM; Egorin, M; Gervais, A; Warren, K, 2004)		0.32
" The starting dosage of CPT-11 was 15 mg/m2 per day (days 1-3 and 8-10), and dosage-escalation increments of 5 mg/m2 per day were planned, with fixed dosages of carboplatin (250 mg/m2 per day, day 1) and dexamethasone (40 mg/body, days 1-3 and days 8-10)."( Phase I study of the combination of irinotecan hydrochloride, carboplatin, and dexamethasone for the treatment of relapsed or refractory malignant lymphoma.
Maeda, K; Okamura, S; Shibuya, T; Suzumiya, J; Suzushima, H; Tamura, K; Utsunomiya, A, 2004)		0.32
" Depending on dosage and agent used symptoms resolve completely or not."( [Neurotoxic effects of medications: an update].
Arné-Bès, MC, 2004)		0.32
" Although deviation was observed between the predicted and observed neutrophil counts in ovarian cancer patients, it may be possible to use this model for determining a rational dosage regimen of rhG-CSF for patients undergoing chemotherapy."( Pharmacokinetic/pharmacodynamic analysis of neutrophil proliferation induced by rhG-CSF in patients receiving antineoplastic drugs.
Iga, T; Ohno, Y; Sugiura, M; Suzuki, H; Yamada, Y, 2004)		0.32
" Although the study exhibited a high response rate, the neuropathy encountered in the study, and the need to eliminate gemcitabine in 54% of the patients due to bone marrow suppression merits further investigation of the dosing schedule."( Pilot study of outpatient paclitaxel, carboplatin and gemcitabine for advanced stage epithelial ovarian, peritoneal, and fallopian tube cancer.
Birk, CL; Brown, JV; Goldstein, BH; Graham, C; Mattison, J; Micha, JP; Rettenmaier, MA, 2004)		0.32
" BMS-275291 or placebo was administered on an outpatient basis at a daily oral dosage of 1200 mg."( Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer.
Arnold, A; Davis, M; Douillard, JY; Humphrey, J; Ottaway, J; Paz-Ares, L; Peschel, C; Seymour, L; Shepherd, F; Smylie, M; Tonato, M; Tu, D; Voi, M; Vreckem, AV; Young, K, 2004)		0.32
"In cats, an individualized prescription strategy for carboplatin administration based on a targeted AUC and determination of GFR might more uniformly predict myelosuppression than that predicted by conventional dosing based on body surface area."( Effect of glomerular filtration rate on clearance and myelotoxicity of carboplatin in cats with tumors.
Bailey, DB; Dykes, NL; Erb, HN; Hoopes, PJ; Page, RL; Rassnick, KM, 2004)		0.32
"Thirty-two patients with metastatic NPC were treated with combination chemotherapy that included paclitaxel 70 mg/m(2) on Days 1 and 8, carboplatin dosed to area under curve of 5 on Day 1, and gemcitabine 1000 mg/m(2) on Days 1 and 8 every 21 days for a maximum of 8 cycles."( Paclitaxel, carboplatin, and gemcitabine in metastatic nasopharyngeal carcinoma: a Phase II trial using a triplet combination.
Foo, KF; Leong, SS; Lim, WT; Tan, EH; Tan, SB; Tan, T; Tay, MH; Thng, CH; Toh, CK; Wee, J, 2005)		0.33
"Bayesian pharmacokinetically guided dosing for CTC was feasible and led to a marked reduction in variability of exposure."( Accuracy, feasibility, and clinical impact of prospective Bayesian pharmacokinetically guided dosing of cyclophosphamide, thiotepa, and carboplatin in high-dose chemotherapy.
Beijnen, JH; de Jonge, ME; Huitema, AD; Rodenhuis, S; Tukker, AC; van Dam, SM, 2005)		0.33
"Many investigations have focused on an optimal dosing schedule for paclitaxel since its regulatory approval."( A simplified premedication schedule for 1-hour paclitaxel administration.
Kosmas, C; Tsavaris, N; Vadiaka, M, )		0.13
"To study the reasonable dosage for paraplatin according to different dosage calculations."( [Treatment of non-small-cell lung cancer with paraplatin given by two different dosage calculation methods].
Cheng, C; Feng, WN; Gu, LJ; Huang, SH; Weng, YM; Wu, YL; Yang, P; Zhong, WZ, 2005)		0.33
" In group A, paraplatin dosage was calculated according to patients' body surface, and in group B, it was calculated according to the area under the curve (AUS)."( [Treatment of non-small-cell lung cancer with paraplatin given by two different dosage calculation methods].
Cheng, C; Feng, WN; Gu, LJ; Huang, SH; Weng, YM; Wu, YL; Yang, P; Zhong, WZ, 2005)		0.33
" However, patient self-assessments suggested a possible advantage to AM that is being explored with modified dosing route strategies."( Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01.
Axelrod, R; Byhardt, R; Komaki, R; Langer, C; Machtay, M; Movsas, B; Nicolaou, N; Sarna, L; Scott, C; Smith, C; Wasserman, T; Werner-Wasik, M, 2005)		0.33
" Three patients were treated at each dosing level (AUC=2-6), and 4 patients were treated at an AUC=5."( A phase I trial of surgery, Gliadel wafer implantation, and immediate postoperative carboplatin in combination with radiation therapy for primary anaplastic astrocytoma or glioblastoma multiforme.
Asher, A; Fraser, R; Heafner, M; Kim, JW; Limentani, SA, 2005)		0.33
" The weekly dosing used in this trial warrants further investigation as an alternative first-line approach in patients with poor renal reserve and/or performance status or as a second-line management of advanced TCC."( Phase II trial of weekly paclitaxel and carboplatin chemotherapy in patients with advanced transitional cell cancer.
Hinke, A; Johannsen, M; Loening, SA; Roigas, J; Sachs, M; Schnorr, D; Staack, A; Wille, AH, 2005)		0.33
" The carboplatin dosage was calculated by using the Chatelut formula."( A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy.
Fujiwara, Y; Kasamatsu, T; Katsumata, N; Tsunematsu, R; Yamada, T; Yamamoto, N; Yonemori, K, 2005)		0.33
" Pharmacologic studies demonstrated that administration of the dosage estimated with the Chatelut formula instead of the Chatelut formula with adjustment for serum creatinine resulted in a slightly excessive dose of carboplatin."( A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy.
Fujiwara, Y; Kasamatsu, T; Katsumata, N; Tsunematsu, R; Yamada, T; Yamamoto, N; Yonemori, K, 2005)		0.33
" Retardation of the electrophoretic migration on agarose gel of drug-treated DNA, in the dose-response manner, was observed."( In vitro platination of human breast cancer suppressor gene1 (BRCA1) by the anticancer drug carboplatin.
Canyuk, B; Mahasawat, P; Ratanaphan, A; Wasiksiri, S, 2005)		0.33
"When determining the carboplatin dosage from the Calvert formula, there are a lack of data when evaluating patients with cachexia or body mass index (BMI)>or=27."( Prospective evaluation of carboplatin AUC dosing in patients with a BMI>or=27 or cachexia.
Herrington, JD; Riggs, MW; Tran, HT, 2006)		0.33
" Significant interpatient variability in the topotecan systemic exposure results when it is dosed based on body surface area (mg/m2)."( A phase I trial defining the maximum tolerated systemic exposure of topotecan in combination with Carboplatin and Etoposide in extensive stage small cell lung cancer.
Donahue, A; Faucette, S; Gillenwater, HH; Kirstein, MN; Lindley, C; McCune, JS; Moore, D; Shord, S; Socinski, MA; Stewart, CF; Zamboni, WC, 2005)		0.33
" Topotecan was administered as a 30-minute infusion either on Days 1-5 or Days 1-3 and the dosage was individualized to attain a topotecan lactone AUC range (ng/mL*hr) in successive patient cohorts from 7 to 23; 24 to 36; 37 to 53; 54 to 66."( A phase I trial defining the maximum tolerated systemic exposure of topotecan in combination with Carboplatin and Etoposide in extensive stage small cell lung cancer.
Donahue, A; Faucette, S; Gillenwater, HH; Kirstein, MN; Lindley, C; McCune, JS; Moore, D; Shord, S; Socinski, MA; Stewart, CF; Zamboni, WC, 2005)		0.33
" To improve treatment, voriconazole dosage was adapted to reach drug concentrations in cerebrospinal fluid (CSF) above the minimal fungicidal concentration and plasma specimens."( Successful treatment with voriconazole of Aspergillus brain abscess in a boy with medulloblastoma.
Burhenne, J; Foell, JL; Reiss, T; Rengelshausen, J; Staege, MS; Stiefel, M; Wawer, A, 2007)		0.34
"The aim of this study was the development of a veterinary dosage form constituted by injectable biodegradable microspheres designed for the subcutaneous release of carboplatin, a chemotherapeutic drug."( Spray-dried poly(D,L-lactide) microspheres containing carboplatin for veterinary use: in vitro and in vivo studies.
Achenza, G; Gavini, E; Giua, S; Giunchedi, P; Manunta, L, 2005)		0.33
"The individual dosing of drugs that are mainly eliminated unchanged in the urine is made possible by assessing renal function."( Cystatin C as a new covariate to predict renal elimination of drugs: application to carboplatin.
Bugat, R; Chatelut, E; Dalenc, F; Durrand, V; Gladieff, L; Lafont, T; Malard, L; Poublanc, M; Séronie-Vivien, S; Thomas, F, 2005)		0.33
" The reduction of tumor burden followed a U-shaped dose-response curve."( Anecortave acetate as single and adjuvant therapy in the treatment of retinal tumors of LH(BETA)T(AG) mice.
Escalona-Benz, E; Feuer, W; Hernandez, E; Jockovich, ME; Murray, TG, 2006)		0.33
"0%, with no significant differences between those treated with C3DRT versus IMRT, nor between the two radiation dosing schemes."( Intensity-modulated radiation therapy in advanced head and neck patients treated with intensive chemoradiotherapy: preliminary experience and future directions.
Chmura, SJ; Dekker, A; Garofalo, MC; Haraf, DJ; Jackson, W; Kao, J; List, MA; MacCracken, E; Milano, MT; Stenson, KM; Vokes, EE; Weichselbaum, RR; Witt, ME, 2006)		0.33
" This study was designed to develop and evaluate the performance of an alternative CBDCA 120-hour schedule coupled to a Bayesian adaptive dosing with feedback strategy."( Dose individualization of carboplatin after a 120-hour infusion schedule: higher dose intensity but fewer toxicities.
Baciuchka, M; Bagarry-Liegey, D; Ciccolini, J; Digue, L; Duffaud, F; Durand, A; Fanciullino, R; Favre, R; Guillet, P; Lacarelle, B; Mercier, C; Monjanel-Mouterde, S; Nicoara, A; Noble, A; Pourroy, B; Tranchand, B, 2006)		0.33
" 5-fluoruracil 750 mg sq m(-1), leucovorin 75 mg sq m(-1), epirubicin 45 mg sq m(-1), carboplatin 225 mg sq m(-1) were administered every 3 weeks into celiac axis for three cycles (FLEC regimen), then gemcitabine at the dosage of 1 g sq m(-1) on days 1, 8 and 15 every 4 weeks for 3 months (FLECG regimen)."( Adjuvant intra-arterial 5-fluoruracil, leucovorin, epirubicin and carboplatin with or without systemic gemcitabine after curative resection for pancreatic adenocarcinoma.
Cantore, M; Capelli, P; Fiorentini, G; Iacono, C; Lombardi, M; Mambrini, A; Pacetti, P; Pagani, M; Pederzoli, P; Pulica, C; Serio, G; Torri, T, 2006)		0.33
" Fixed dose rate gemcitabine is active and feasible, supporting the concept of fixed dosing rate of gemcitabine in advanced NSCLC."( A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer.
Beale, P; Boyer, M; Goh, BC; Lee, HS; Lee, SC; Liang, S; Lim, HL; Millward, M; Soo, RA; Tham, LS; Wang, LZ; Yong, WP, 2006)		0.33
" A dosing nomogram was developed by using population-based pharmacokinetic analysis of phase I results (15 patients, 85 treatment cycles), and evaluated in phase II patients (19 females, 28 males, 196 treatment cycles)."( Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development.
Au, JL; Chen, D; Grever, M; Jensen, R; Murgo, AJ; Otterson, GA; Song, SH; Villalona-Calero, M; Wientjes, MG; Yeh, TK; Zhao, L, 2006)		0.33
" The dosing nomogram, incorporating body surface area as the major covariate of intersubject variability and the time elapsed since the previous dose (to account for the residual concentrations due to the slow elimination), delivered the target concentrations in >95% of treatments."( Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development.
Au, JL; Chen, D; Grever, M; Jensen, R; Murgo, AJ; Otterson, GA; Song, SH; Villalona-Calero, M; Wientjes, MG; Yeh, TK; Zhao, L, 2006)		0.33
"The present study identified and validated a dosing nomogram and schedule to deliver low and nontoxic suramin concentrations that produce chemosensitization in preclinical models."( Nontoxic suramin as a chemosensitizer in patients: dosing nomogram development.
Au, JL; Chen, D; Grever, M; Jensen, R; Murgo, AJ; Otterson, GA; Song, SH; Villalona-Calero, M; Wientjes, MG; Yeh, TK; Zhao, L, 2006)		0.33
" To optimize radiotherapy, dosage was reduced by 10% or daily single target dose of intracavitary and distant irradiation split per 24 hrs, indications for preoperative radiotherapy variants were extended, and local dosage escalation in areas of lymphocyst or hematoma renounced."( [Improvement of postoperative radiotherapy in the complex treatment of stage II-III cervical cancer].
Kreĭnina, IuM; Povarova, EV; Shevchenko, LN; Shipilova, AN; Titova, VA, 2006)		0.33
" Taken together, our data provide the basis for potential therapeutic application of MCD in combination with other conventional cytotoxic drugs to facilitate reduction of drug dosage that offers a better chemotherapeutic approach with low toxicity."( Methyl-beta-cyclodextrin enhances the susceptibility of human breast cancer cells to carboplatin and 5-fluorouracil: involvement of Akt, NF-kappaB and Bcl-2.
Ajay, AK; Bhat, MK; Chhipa, RR; Singh, S; Upadhyay, AK; Vijayakumar, MV, 2006)		0.33
" We investigated the pharmacokinetics of carboplatin in Japanese prostate cancer patients (n=10, 55-72 years), and evaluated the usefulness of Calvert's formula in the individualized dosing adjustment."( Evaluation of Calvert's formula for dosage adjustment of carboplatin in Japanese patients with hormone refractory prostate cancer.
Inui, K; Ito, N; Jiko, M; Kamoto, T; Katsura, T; Masuda, S; Motohashi, H; Nishiyama, H; Ogawa, O; Sato, E; Segawa, T; Takahashi, K; Yano, I, 2006)		0.33
"Carboplatin dosing is usually based on glomerular filtration rate (GFR)."( Evaluation of predictive formulae for glomerular filtration rate for carboplatin dosing in gynecological malignancies.
Conklin, J; de Lemos, ML; Djurdjev, O; Hamata, L; Hsieh, T; Hu, F; Levin, A; Malfair Taylor, SC; Swenerton, K; Vu, T, 2006)		0.33
"To evaluate the efficacy and dose-response of transcorneoscleral Coulomb controlled iontophoresis (CCI) of carboplatin in the treatment of retinal tumors of a murine model of retinoblastoma."( Iontophoretic delivery of carboplatin in a murine model of retinoblastoma.
Feuer, W; Hayden, B; Hernandez, E; Jockovich, ME; Kralinger, MT; Murray, TG; Parel, JM; Voigt, M, 2006)		0.33
" Due to the dosage for carboplatin by AUC an adaptation to the glomerular filtration rate is possible."( [Gemcitabine and carboplatin chemotherapy in advanced transitional cell carcinoma in regard to patients with impaired renal function].
Helke, C; Hoschke, B; May, M, 2006)		0.33
" In regard to the dosing schedule, premedication was performed as defined before TXL administration, and TXL and CBDCA were administered, in that order, by intravenous infusion for over at least 1 hour."( [Combined chemotherapy with weekly paclitaxel and carboplatin for recurrent and refractory epithelial ovarian cancer--phase I study].
Misawa, A; Yasuda, M, 2006)		0.33
"The Calvert formula is a widely applied algorithm for the a priori dosing of carboplatin based on patients glomerular filtration rate (GFR) as accurately measured using the 51Cr-EDTA clearance."( Flat dosing of carboplatin is justified in adult patients with normal renal function.
Beijnen, JH; de Jonge, ME; Ekhart, C; Huitema, AD; Rodenhuis, S; Schellens, JH, 2006)		0.33
"Our data do not support the application of modifications of the Calvert formula by estimating GFR from SCR in the a priori dosing of carboplatin in patients with relatively normal renal function (creatinine clearance, >50 mL/min)."( Flat dosing of carboplatin is justified in adult patients with normal renal function.
Beijnen, JH; de Jonge, ME; Ekhart, C; Huitema, AD; Rodenhuis, S; Schellens, JH, 2006)		0.33
" The tumours with a TOP2A amplification contributed hardly to this difference, suggesting that TOP2A amplification is not the cause of the steep dose-response curve for anthracyclines in breast cancer."( Molecular subtypes of breast cancer and amplification of topoisomerase II alpha: predictive role in dose intensive adjuvant chemotherapy.
Bontenbal, M; de Vries, EG; Hannemann, J; Hupperets, P; Kristel, P; Nooij, MA; Rodenhuis, S; Smit, WM; van de Vijver, MJ; van der Wall, E; van Hoesel, QG; van Tinteren, H; Voest, EE, 2006)		0.33
" Mesna was applied at a dosage of 20% of ifosfamide 3 times at 4-hour intervals after termination of the ifosfamide infusion."( [Efficacy of chemotherapy regimen using ifosphamide and carboplatin on recurrent or refractory neuroblastoma].
Ling, JY; Sun, XF; Wang, ZH; Xia, Y; Zhen, ZJ, 2006)		0.33
" Real-time monitoring of carboplatin pharmacokinetics with adaptive dosing is both feasible and necessary for the attainment of consistent AUC values in children receiving high-dose carboplatin treatment."( Adaptive dosing and platinum-DNA adduct formation in children receiving high-dose carboplatin for the treatment of solid tumours.
Boddy, AV; Ellershaw, C; Errington, J; Foot, AB; McDowell, H; Nowell, GM; Pearson, AD; Pearson, DG; Pizer, B; Tilby, MJ; Veal, GJ, 2007)		0.34
" In lung cancer, flattening of dose-response curves at higher doses suggests that efficacy is limited by exhaustion of something required for cell killing, and several clinical observations suggest epigenetic events may play a major role in resistance."( Mechanisms of resistance to cisplatin and carboplatin.
Stewart, DJ, 2007)		0.34
"This overview follows on from part I, which described the current practices used in chemotherapy dosing and the paucity of scientific evidence to support them."( Chemotherapy dosing part II: alternative approaches and future prospects.
Kaestner, SA; Sewell, GJ, 2007)		0.34
" Pemetrexed dosing was 500 mg/m and carboplatin was AUC (area under the curve) 5 once every 3 weeks."( Pemetrexed as second-line treatment in malignant pleural mesothelioma after platinum-based first-line treatment.
Perell, K; Sundstrøm, S; Sørensen, JB; Thielsen, AK, 2007)		0.34
" In the Phase I portion, the starting dosage of PR-350 was 10 daily administrations (2000 mg/m(2)) in combination with RT, and this number was increased in increments of 10 for successive groups to 30 doses."( Phase I/II trial of sequential chemoradiotherapy using a novel hypoxic cell radiosensitizer, doranidazole (PR-350), in patients with locally advanced non-small-cell lung Cancer (WJTOG-0002).
Ariyoshi, Y; Fukuoka, M; Fuwa, N; Hida, T; Hirokawa, K; Katakami, N; Kawahara, M; Nakagawa, K; Negoro, S; Nishimura, Y; Segawa, Y; Takeda, K; Tanaka, M; Tsujino, K; Yamamoto, N, 2007)		0.34
"Despite evidence in the literature suggesting that a strong correlation exists between the pharmacokinetic parameters and pharmacodynamic effect of anticancer agents, many of these agents are still dosed by body surface area."( A systematic review of limited sampling strategies for platinum agents used in cancer chemotherapy.
Ensom, MH; Loh, GW; Ting, LS, 2007)		0.34
" As a result, both the toxicity and efficacy of over 30 anticancer agents vary by more than 50% as a function of dosing time in experimental models."( Implications of circadian clocks for the rhythmic delivery of cancer therapeutics.
Baron, B; de la Valette, V; Focan, C; Focan-Henrard, D; Giacchetti, S; Karaboué, A; Kreutz, F; Lévi, F, 2007)		0.34
" No DB-scheme has been reported for carboplatin, which, in clinical practice, is routinely dosed according to renal function."( Dose-banding of carboplatin: rationale and proposed banding scheme.
Kaestner, S; Sewell, G, 2007)		0.34
"To assess the rationale for DB of carboplatin with regards to factors that influence dosing accuracy, develop a DB scheme, and discuss its potential use and limitations."( Dose-banding of carboplatin: rationale and proposed banding scheme.
Kaestner, S; Sewell, G, 2007)		0.34
"To analyse carboplatin dosage in cancer patients in order to establish whether they are over- or underdosed in comparison to the theoretical dose calculations during the first cycle of chemotherapy and to find a relationship between the dosage in the first cycle and dose reduction in subsequent cycles, as a result of adverse effects related to the same."( [Retrospective analysis of the carboplatin dosage and relationship with toxicity in cancer patients].
Castellanos Clemente, Y; Díez Fernández, R; García Palomo, M; Hernández Muniesa, B; Iglesias Bolaños, AM; Martínez Sesmero, JM, )		0.13
" The Mann-Whitney U test was used to study the possible relationship between patients dosage during the first cycle and dose reduction in subsequent cycles."( [Retrospective analysis of the carboplatin dosage and relationship with toxicity in cancer patients].
Castellanos Clemente, Y; Díez Fernández, R; García Palomo, M; Hernández Muniesa, B; Iglesias Bolaños, AM; Martínez Sesmero, JM, )		0.13
" Further study is needed for a selection of suitable chemotherapeutic regimens, an optimal dosage of each drug and timing of hemodialysis."( [Carboplatin and CPT-11 chemotherapy in a hemodialysis patient with small-cell lung cancer].
Baba, M; Hayashi, N; Kakimoto, Y; Koshiishi, H; Koshiishi, Y; Minami, T; Okamura, T; Takahashi, E; Yasui, T, 2007)		0.34
"To preliminarily determine the appropriate dosage of carboplatin (CBP) at AUC of 5 mg."( Determination of carboplatin dose by area under the curve in combination chemotherapy for senile non-small cell lung cancer.
Hu, C; Liu, Q; Yin, T, 2007)		0.34
" Age, performance status and other geriatric parameters should be considered when dosing chemotherapy in the elderly."( Improved tolerance of primary chemotherapy with reduced-dose carboplatin and paclitaxel in elderly ovarian cancer patients.
Abushahin, F; Belinson, J; Fader, AN; Gibbons, H; Markman, M; Rose, P; Starks, D; von Gruenigen, V, 2008)		0.35
" These data may aid the design of studies to clarify optimal dosing and leukapheresis with pegfilgrastim."( A phase 2 pilot study of pegfilgrastim and filgrastim for mobilizing peripheral blood progenitor cells in patients with non-Hodgkin's lymphoma receiving chemotherapy.
Baker, N; Barker, P; Boogaerts, M; Canizo, CD; Johnsen, HE; Mesters, R; Russell, N; Schmitz, N; Schubert, J; Skacel, T, 2008)		0.35
" The dose of carboplatin was determined by a measured glomerular filtration rate (GFR), ensuring accurate dosing in all categories of BMI and the dose of taxane was not capped."( Does body mass index affect progression-free or overall survival in patients with ovarian cancer? Results from SCOTROC I trial.
Barrett, SV; Glasspool, RM; Hay, A; Kaye, SB; Paul, J; Vasey, PA, 2008)		0.35
"The dosage of carboplatin in cats has been reported anecdotally and experimentally in non-tumor-bearing cats, but the dosage for carboplatin treatment in tumor-bearing cats has yet to be defined in a prospective clinical trial."( Phase I clinical evaluation of carboplatin in tumor-bearing cats: a Veterinary Cooperative Oncology Group study.
Couto, CG; Jeglum, KA; Khanna, C; Kisseberth, WC; Obradovich, JE; Vail, DM; Ward, H; Yaissle, J, )		0.13
"Carboplatin dosing for gynecologic malignancies is traditionally based on the Jelliffe formula that lacks dose adjustment for weight."( Carboplatin dosing in obese women with ovarian cancer: a Gynecologic Oncology Group study.
Fujiwara, K; Herzog, TJ; Mutch, DG; Nagao, S; Powell, MA; Tian, C; Wright, JD, 2008)		0.35
" In patients with abnormal renal function, dosage adjustment is often required to improve the renal tolerance, and also to limit the risk of extra-renal toxicities (such as haematological toxicities) induced by a drug overdosage, in those patients with reduced drug-elimination."( [Chemotherapy and renal toxicity].
Deray, G; Isnard-Bagnis, C; Janus, N; Karie, S; Launay-Vacher, V, 2008)		0.35
" A number of preclinical and early clinical studies have evaluated the feasibility, duration, and appropriate dosing schedule(s) for taxane-trastuzumab combinations in HER-2-positive metastatic breast cancer."( Clinical efficacy of taxane-trastuzumab combination regimens for HER-2-positive metastatic breast cancer.
Blackwell, K; Bullock, K, 2008)		0.35
"Carboplatin dosing based on renal function and therapeutic monitoring have been previously shown to be beneficial in the treatment of children with cancer."( Therapeutic monitoring of carboplatin dosing in a premature infant with retinoblastoma.
Boddy, AV; Errington, J; Holden, V; Keeble, J; Picton, SV; Veal, GJ, 2009)		0.35
" Pharmacokinetically-guided carboplatin dosing led to the attainment of AUCs within 10% of target values on each course of treatment."( Therapeutic monitoring of carboplatin dosing in a premature infant with retinoblastoma.
Boddy, AV; Errington, J; Holden, V; Keeble, J; Picton, SV; Veal, GJ, 2009)		0.35
" The aims of this study were (i) to develop a pharmacokinetic-pharmacodynamic (PK-PD) model to describe the myelosuppressive effect of the combination, and (ii) to use this model to select a dosing regimen for Phase II evaluation."( Population pharmacokinetic and pharmacodynamic analysis to support treatment optimization of combination chemotherapy with indisulam and carboplatin.
Beijnen, JH; Dittrich, C; Huitema, AD; Schellens, JH; Wanders, J; Zandvliet, AS, 2008)		0.35
"The carboplatin (CBDCA) dosage is usually calculated using the formula of Calvert."( [Study of the predictive method of 24-hour creatinine clearance in calculating the appropriate dosage of Carboplatin].
Hirai, R; Homma, S; Isobe, K; Kishino, S; Koshikawa, I; Ohno, K; Shimano, Y; Suga, N, 2008)		0.35
"We studied the adequacy of 24 CLcr in calculating the appropriate dosage of CBDCA using the formula of Calvert and compared CLcr and GFR using various substitutable predictive formulas (the formulae of Cockcroft and Gault, Yasuda, Orita, Jellife, Mawer, MDRD, and modified MDRD) when we were not able to use 24 CLcr."( [Study of the predictive method of 24-hour creatinine clearance in calculating the appropriate dosage of Carboplatin].
Hirai, R; Homma, S; Isobe, K; Kishino, S; Koshikawa, I; Ohno, K; Shimano, Y; Suga, N, 2008)		0.35
"The results of our study have shown that weekly carboplatin at this dosage is a safe way to deliver synchronous chemotherapy during RT for MCC and results in a marked reduction of febrile neutropenia and Grade 3 skin toxicity compared with the three weekly regimen."( Weekly carboplatin reduces toxicity during synchronous chemoradiotherapy for Merkel cell carcinoma of skin.
Dickie, G; Harvey, J; Keller, J; O'Brien, P; Poulsen, M; Rischin, D; Tripcony, L; Walpole, E, 2008)		0.35
"Renal function-based carboplatin dosing is used routinely in paediatric oncology clinical practice."( Estimation of renal function and its potential impact on carboplatin dosing in children with cancer.
Boddy, AV; Chinnaswamy, G; Cole, M; English, M; Keir, M; Parry, A; Price, L; Veal, GJ, 2008)		0.35
"This phase II, single arm, multi-institution study featured standard dosage of cetuximab 400 mg/m day 1, then 250 mg/m with paclitaxel (100 mg/m/wk, for 3 weeks), and carboplatin (area under curve = 6) day 1 of each 28 day cycle."( Phase II study of paclitaxel, carboplatin, and cetuximab as first line treatment, for patients with advanced non-small cell lung cancer (NSCLC): results of OPN-017.
Borghaei, H; Cohen, R; Langer, CJ; Litwin, S; Millenson, M; Mintzer, D; Rovito, M; Ruth, KJ; Seldomridge, JS; Treat, J; Tuttle, H, 2008)		0.35
" Carboplatin dosage was based on glomerular filtration rate (GFR) to achieve targeted systemic exposure (6mg/ml min)."( Renal function after ifosfamide, carboplatin and etoposide (ICE) chemotherapy, nephrectomy and radiotherapy in children with Wilms tumour.
Daw, NC; Gregornik, D; Jenkins, JJ; Jones, DP; Kun, LE; Marina, N; McPherson, V; Rodman, J; Wilimas, J; Wu, J, 2009)		0.35
"Traditionally, carboplatin dosage is based on the Calvert formula."( Evaluation of carboplatin dosage based on 4-variable modification of diet in renal disease equation.
Barry, A; Donnellan, P; Griffin, D; Grimes, H; Keane, M; O'Cearbhaill, R, 2009)		0.35
"We performed a retrospective analysis of carboplatin dosage in our institute."( Evaluation of carboplatin dosage based on 4-variable modification of diet in renal disease equation.
Barry, A; Donnellan, P; Griffin, D; Grimes, H; Keane, M; O'Cearbhaill, R, 2009)		0.35
"The MDRD derived eGFR is readily available and may prove very useful in calculating carboplatin dosage for patients with impaired renal function."( Evaluation of carboplatin dosage based on 4-variable modification of diet in renal disease equation.
Barry, A; Donnellan, P; Griffin, D; Grimes, H; Keane, M; O'Cearbhaill, R, 2009)		0.35
" Since all these measures are accompanied by relatively low risks of chronic bleeding a choice of palliative or radical dosage of radiation is possible."( [Intra-arterial chemotherapy and chemoembolization in the combined treatment for locally advanced carcinoma of the head and neck].
Korytova, LI; Sokurenko, VP; Suvorova, IuV; Tarazov, PG, 2008)		0.35
" When administered at high dosage or to patients with reduced renal function, Carbo-Pt may be nephrotoxic."( Dose individualization can minimize nephrotoxicity due to carboplatin therapy in patients with ovarian cancer.
Ardini, M; Cosio, S; Donadio, C; Fanucchi, A; Gadducci, A; Lucchesi, A, 2009)		0.35
"Plasma and microdialysate samples from tumor and adipose normal tissues were collected up to 47 h after dosing in eight carboplatin-treated patients with an accessible (sub)cutaneous tumor."( Application of prolonged microdialysis sampling in carboplatin-treated cancer patients.
Engels, FK; Konings, IR; Loos, WJ; Sleijfer, S; Verweij, J; Wiemer, EA, 2009)		0.35
" This study demonstrates that the combined modality resulted in enhanced apoptotic cell death as well as cytotoxic effect on AMC-HN-3 cells in vitro, which suggests the feasibility of combined modality and the possibility of reducing the effective dosage of 9-HPbD and CBDCA and lowering the side effects on normal cells."( Enhanced apoptotic effect of combined modality of 9-hydroxypheophorbide alpha-mediated photodynamic therapy and carboplatin on AMC-HN-3 human head and neck cancer cells.
Ahn, JC; Chung, PS; He, P; Hwang, HJ; Kang, JW; Lee, SJ; Shin, JI, 2009)		0.35
" Further work is indicated to determine optimal dosing regimens, maximal tolerated dosage, and subsequent visual function in these patients."( Persistence of retinal function after selective ophthalmic artery chemotherapy infusion for retinoblastoma.
Abramson, DH; Brodie, SE; Dunkel, IJ; Kim, JW; Pierre Gobin, Y, 2009)		0.35
" Criteria for inclusion were administration of radiation according to 1 of 3 fractionation schemes (19 x 3, 16 x 3, or 12 x 4 Gy) and administration of at least 1 concurrent carboplatin treatment at a dosage of 200-300 mg/m(2)."( Adverse effects of concurrent carboplatin chemotherapy and radiation therapy in dogs.
Hume, KR; Johnson, JL; Williams, LE, )		0.13
"Median carboplatin dosage was 200 mg/m(2) (range, 200-250 mg/m(2))."( Adverse effects of concurrent carboplatin chemotherapy and radiation therapy in dogs.
Hume, KR; Johnson, JL; Williams, LE, )		0.13
" Response rate in this study was modest, and optimization of dosing of this combination is required."( Combined gemcitabine and carboplatin therapy for carcinomas in dogs.
Cadile, CD; Dervisis, NG; Dominguez, PA; Kitchell, BE; Sarbu, L, )		0.13
"Serum creatinine (SCr)-based formulas are used to estimate glomerular filtration rate (GFR) when calculating a dosage for carboplatin using the Calvert equation, but these formulas often underestimate measured GFR."( Evaluation of the Modified Diet in Renal Disease equation for calculation of carboplatin dose.
Bressler, LR; Chen, N; Radhakrishnan, L; Shord, SS; Villano, JL, 2009)		0.35
"To determine the absolute difference between the dose of carboplatin administered (traditional SCr-based formulas used to estimate GFR) and the dose calculated using the MDRD equation to estimate GFR and compare the frequencies of thrombocytopenia, neutropenia, and dosage modifications between subjects in whom the difference in dose was 20% or more (divergent) or less than 20% (nondivergent)."( Evaluation of the Modified Diet in Renal Disease equation for calculation of carboplatin dose.
Bressler, LR; Chen, N; Radhakrishnan, L; Shord, SS; Villano, JL, 2009)		0.35
" The frequencies of neutropenia, thrombocytopenia, and dosage modifications were similar between the 2 groups."( Evaluation of the Modified Diet in Renal Disease equation for calculation of carboplatin dose.
Bressler, LR; Chen, N; Radhakrishnan, L; Shord, SS; Villano, JL, 2009)		0.35
"The traditional SCr-based formulas for the calculation of carboplatin dosage should be used to estimate carboplatin dose until more data become available regarding the use of the MDRD equation in this population."( Evaluation of the Modified Diet in Renal Disease equation for calculation of carboplatin dose.
Bressler, LR; Chen, N; Radhakrishnan, L; Shord, SS; Villano, JL, 2009)		0.35
" The weakness around body surface area-based dosing was a commonly discussed topic."( A national survey investigating UK prescribers' opinions on chemotherapy dosing and 'dose-banding'.
Kaestner, SA; Sewell, GJ, 2009)		0.35
" The sequence was repeated twice during 2 hours based on previous published studies which optimized the cisplatin dosage and exposure duration."( Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer.
Chauffert, B; Combe, M; Delroeux, D; Demarchi, M; Guardiola, E; Heyd, B; Lorgis, V; Pivot, X; Royer, B; Stein, U, 2009)		0.35
" Dosing schemas were based on the maximum-tolerated dose derived in a previous phase I study."( Phase II trial of irinotecan and carboplatin for extensive or relapsed small-cell lung cancer.
Chen, G; Fehrenbacher, L; Gandara, D; Goldstein, D; Huynh, M; Lara, PN; Lau, D; Russin, M; West, H; Yavorkovsky, LL, 2009)		0.35
" This study was designed to assess combining this immunotherapy at 2 dosing schedules with front-line chemotherapy in patients with advanced ovarian cancer."( The Immune adjuvant properties of front-line carboplatin-paclitaxel: a randomized phase 2 study of alternative schedules of intravenous oregovomab chemoimmunotherapy in advanced ovarian cancer.
Braly, P; Chu, C; Collins, Y; Edwards, R; Gordon, A; McGuire, W; Method, M; Nicodemus, CF; Schoonmaker, C; Smith, LM; Whiteside, T, 2009)		0.35
"Although many clinicians practice empiric dose reduction to prevent toxicity, it is unknown whether obese patients given chemotherapy dosed according to actual body weight (ABW) experience excess toxicity."( Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.
Dizon, DS; Schwartz, J; Toste, B, 2009)		0.35
" Records were reviewed for patient age, BSA, diagnosis, stage, standardized and actual doses for each cycle, adverse drug reactions, and dosing modifications."( Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.
Dizon, DS; Schwartz, J; Toste, B, 2009)		0.35
" 50 received paclitaxel dosed by ABW and 9 received paclitaxel capped at a BSA of 2 m(2)."( Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.
Dizon, DS; Schwartz, J; Toste, B, 2009)		0.35
"Obese women with a BSA>2 m(2) on paclitaxel dosed by ABW do not experience excess toxicity in comparison to women on paclitaxel capped at a maximum BSA or women in published trials of adjuvant P/C."( Chemotherapy toxicity in gynecologic cancer patients with a body surface area (BSA)>2 m2.
Dizon, DS; Schwartz, J; Toste, B, 2009)		0.35
"For the first time, a unique formula is proposed for carboplatin individual dosing to patients, which is shown to be equally valid for underweight, normal weight, and obese patients."( A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients.
Billaud, E; Bobin-Dubigeon, C; Boisdron-Celle, M; Bougnoux, P; Campone, M; Capitain, O; Chatelut, E; Etienne-Grimaldi, MC; Fabbro, M; Floquet, A; Gladieff, L; Houede, N; Lansiaux, A; Largillier, R; Le Guellec, C; Lochon, I; Medioni, J; Penel, N; Pinguet, F; Schmitt, A; Serre-Debauvais, F, 2009)		0.35
" Adjustments in gemcitabine dosage during radiotherapy or changes in radiotherapy planning could reduce toxicity."( High frequency of radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent radiotherapy and gemcitabine after induction with gemcitabine and carboplatin.
Arrieta, O; Astorga-Ramos, AM; de la Garza, J; Gallardo-Rincón, D; Martínez-Barrera, L; Michel, RM; Villarreal-Garza, C, 2009)		0.35
" Using nonlinear modeling, dose-response curves and IC50 values were generated for specimens treated with TRA-8."( Effect of TRA-8 anti-death receptor 5 antibody in combination with chemotherapy in an ex vivo human ovarian cancer model.
Alvarez, RD; Buchsbaum, DJ; Della Manna, DL; Frederick, PJ; Grizzle, WE; Kendrick, JE; Lin, HY; LoBuglio, AF; Oliver, PG; Stockard, CR; Straughn, JM; Zhou, T, 2009)		0.35
"Glomerular filtration rate (GFR) is often used to determine initial dosing of renally excreted cancer drugs."( Evaluation of creatinine-based formulas in dosing adjustment of cancer drugs other than carboplatin.
de Lemos, ML; Jennings, S; Levin, A; Murray, N, 2010)		0.36
" The MDRD formula may be a reasonable alternative to the CG formula for dosing of cancer drugs which are renally excreted or nephrotoxic."( Evaluation of creatinine-based formulas in dosing adjustment of cancer drugs other than carboplatin.
de Lemos, ML; Jennings, S; Levin, A; Murray, N, 2010)		0.36
" Etoposide pharmacokinetic data support previous findings that question the utility of modified dosing in infants."( Pharmacokinetics of carboplatin and etoposide in infant neuroblastoma patients.
Boddy, AV; Cole, M; Ellershaw, C; Errington, J; Gerrard, M; Pearson, AD; Veal, GJ; Whyman, G, 2010)		0.36
"Women with stages IIA to IIIB disease received carboplatin dosed by six times the area under the curve every 4 weeks and paclitaxel 80 mg/m(2) weekly for 16 weeks, and weekly trastuzumab was added for human epidermal growth factor receptor 2 (HER2) -positive status."( Frequent pathologic complete responses in aggressive stages II to III breast cancers with every-4-week carboplatin and weekly paclitaxel with or without trastuzumab: a Brown University Oncology Group Study.
Dizon, DS; Fenton, MA; Gass, JS; Graves, TA; Kennedy, TA; Legare, RD; Sikov, WM; Strenger, R; Theall, KP, 2009)		0.35
" Notably, levels of bioactive IGF-1 seemed to influence response to treatment with objective responses in patients with a high baseline-free IGF-1 to IGF binding protein-3 ratio seen only in the 10 and 20 mg/kg dosing cohorts."( Safety, pharmacokinetics, and pharmacodynamics of the insulin-like growth factor type 1 receptor inhibitor figitumumab (CP-751,871) in combination with paclitaxel and carboplatin.
Cardenal, F; Cohen, RB; Demers, L; Eisenberg, PD; Garland, L; Gualberto, A; Haluska, P; Hixon, ML; Karp, DD; Langer, CJ; Leitzel, K; Lipton, A; Paz-Ares, LG; Pollak, MN; Terstappen, LW; Yin, D, 2009)		0.35
" Palmar-plantar erythrodysesthesia, a typical and commonly noted adverse event, rarely occurs when the dosage is 40 mg/m2 iv."( [Pegylated liposomal doxorubicin in ovarian cancer treatment].
Nowak-Markwitz, E, 2009)		0.35
" However, appropriate dosage and time interval between the end of carboplatin administration and the initiation of hemodialysis remain unclear."( Pharmacokinetics of paclitaxel and carboplatin in a hemodialysis patient with advanced ovarian cancer.
Abe, K; Ishiko, O; Sumi, T; Yoshida, H, 2009)		0.35
" In this study, we compared the dosage of carboplatin (CBDCA) calculated using MDRD with that calculated by conservative creatinine clearance (Ccr), and investigated the actual dosage given and the incidence of its adverse effects."( [Clinical evaluation of calculating carboplatin doses using modification of diet in renal disease (MDRD) estimate and adverse events].
Adachi, S; Kimura, M; Matsumoto, R; Matsuoka, T; Nakao, T; Okada, K; Tanaka, Y; Usami, E; Yasuda, T; Yoshimura, T, 2009)		0.35
" The accumulative dosage of carboplatin was 1 900 - 11 400 mg."( [Clinical analysis of thirteen cases of hypersensitivity reactions to carboplatin.].
Huang, HF; Li, Y; Pan, LY; Shen, K; Wang, HB; Wu, M; Yang, JX, 2009)		0.35
"Although for conventional dosing of carboplatin, several strategies are available to individualize the dose based on renal function measurements, such approaches are still rare for high-dose regimens with autologous stem cell support."( Population pharmacokinetics of high-dose carboplatin in children and adults.
Eickhoff, C; Jaehde, U; Kloft, C; Lindauer, A, 2010)		0.36
" An evaluation of the predictive performance of existing a priori dose individualization strategies revealed that flat dosing is appropriate for adult patients with normal renal function receiving a 1-hour infusion."( Population pharmacokinetics of high-dose carboplatin in children and adults.
Eickhoff, C; Jaehde, U; Kloft, C; Lindauer, A, 2010)		0.36
"Thirty-two patients with unresectable stage IIIA/B NSCLC received irinotecan (30 mg/m) and carboplatin dosed to a target area under the concentration curve of 2, each administered weekly for 7 weeks."( Efficacy and toxicity of chemoradiotherapy with carboplatin and irinotecan followed by consolidation docetaxel for unresectable stage III non-small cell lung cancer.
Bastos, BR; Gomez, J; Hatoum, GF; Lopes, G; Raez, LE; Santos, ES; Takita, C; Tolba, K; Walker, GR, 2010)		0.36
" The median cumulative carboplatin dose (mg/m(2)) for patients who received eight cycles using fixed per m(2) dosing was 2151."( Comparison of two methods for carboplatin dosing in children with retinoblastoma.
Allen, S; Billups, C; Haik, BH; Qaddoumi, I; Rodriguez-Galindo, C; Watkins, A; Wilson, MW, 2010)		0.36
" The use of a targeted AUC provides the most accurate method; however, mg per kg of body weight dosing is a very reliable alternative method."( Comparison of two methods for carboplatin dosing in children with retinoblastoma.
Allen, S; Billups, C; Haik, BH; Qaddoumi, I; Rodriguez-Galindo, C; Watkins, A; Wilson, MW, 2010)		0.36
" These results should allow a better individualization of etoposide dosing in children."( Developmental pharmacokinetics of etoposide in 67 children: lack of dexamethasone effect.
Auvrignon, A; Chastagner, P; Corradini, N; Doz, F; Gentet, JC; Giraud, C; Leblond, P; Rey, E; Rubie, H; Treluyer, JM; Urien, S; Vassal, G, 2011)		0.37
" The synergy with docetaxel depended on the treatment sequence; a schedule of MK-2206 dosed before docetaxel was not effective."( MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo.
Hatch, H; Hirai, H; Kotani, H; Majumder, PK; Miyama, K; Nakatsuru, Y; Pan, BS; Sootome, H; Taguchi, S; Tsujioka, K; Ueno, Y, 2010)		0.36
" Patients were stratified by platinum sensitivity and were treated with erlotinib 150 mg daily on a continuous dosing schedule, and carboplatin at an AUC of 5 every 21 days."( A phase II study of erlotinib (OSI-774) given in combination with carboplatin in patients with recurrent epithelial ovarian cancer (NCIC CTG IND.149).
Ellard, SL; Fisher, B; Grimshaw, R; Hirte, H; Oza, A; Seymour, L; Swenerton, K; Tsao, M, 2010)		0.36
" carboplatin dosed at an area-under-the-curve (AUC) of 5 over 60 min on day 1 of a 21-day cycle."( Gemcitabine with carboplatin for advanced biliary tract cancers: a phase II single institution study.
Fournier, CC; James, JS; Picus, J; Suresh, R; Tan, BR; Trinkhaus, K; Williams, KJ, 2010)		0.36
" In some cases, Bayesian adaptative dosing were proposed."( [Level of evidence for therapeutic drug monitoring of carboplatin].
Chatelut, E; Hulin, A; Le Guellec, C; Royer, B, )		0.13
" Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6-8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis."( Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer.
Bach, A; Brufsky, AM; Clawson, A; Conlin, AK; D'Andrea, G; Danso, M; Dickler, M; Hudis, CA; Lake, D; Saleh, M; Seidman, AD; Traina, T, 2010)		0.36
" In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions."( Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer.
Bach, A; Brufsky, AM; Clawson, A; Conlin, AK; D'Andrea, G; Danso, M; Dickler, M; Hudis, CA; Lake, D; Saleh, M; Seidman, AD; Traina, T, 2010)		0.36
"Area under the curve (AUC) dosing is routinely carried out for carboplatin, but the chosen target AUC values remain largely empirical."( Factors for hematopoietic toxicity of carboplatin: refining the targeting of carboplatin systemic exposure.
Billaud, EM; Bobin-Dubigeon, C; Boisdron-Celle, M; Boyer, JC; Chatelut, E; Concordet, D; Durdux, C; Etienne-Grimaldi, MC; Evrard, A; Floquet, A; Gladieff, L; Laffont, CM; Lafont, T; Lansiaux, A; Le Guellec, C; Mazières, J; Mousseau, M; Ollivier, F; Pinguet, F; Schmitt, A, 2010)		0.36
" There were no dose-limiting toxicities reported in all three dosing tiers."( A phase I study of concurrent chemotherapy (paclitaxel and carboplatin) and thoracic radiotherapy with swallowed manganese superoxide dismutase plasmid liposome protection in patients with locally advanced stage III non-small-cell lung cancer.
Argiris, A; Belani, CP; Championsmith, T; Epperly, MW; Gooding, W; Greenberger, JS; Kane, K; Liggitt, D; Luketich, JD; Pennathur, A; Petro, D; Ramalingam, SS; Tarhini, AA; Zhang, X, 2011)		0.37
" To ensure safe and favorable outcomes of treatment, dosing solutions are prepared by appropriate mixing of the drug solutions based on such calculations."( Light-induced deterioration test of carboplatin under clinical settings.
Okamoto, Y; Sanada, Y; Tazumi, K; Tsugane, M; Uejima, E, 2010)		0.36
" Further studies using alternative dose levels could help define an optimal dosing schedule for this treatment combination in patients with platinum-sensitive recurrent disease."( An open-label, single-arm Phase II study of intravenous weekly (Days 1 and 8) topotecan in combination with carboplatin (Day 1) every 21 days as second-line therapy in patients with platinum-sensitive relapsed ovarian cancer.
Hartney, J; Lane, S; Legenne, P; Monk, BJ; Provencher, D; Rose, PG, 2011)		0.37
" Here, we demonstrate for the first time the use of a 3D model for micrometastatic OvCa as a rapid and quantitative reporter to optimize sequence and dosing regimens of clinically relevant combination strategies."( Synergistic enhancement of carboplatin efficacy with photodynamic therapy in a three-dimensional model for micrometastatic ovarian cancer.
Abu-Yousif, AO; Celli, JP; Evans, CL; Finkelstein, D; Hasan, T; Muzikansky, A; Pogue, BW; Rizvi, I, 2010)		0.36
" It was shown that long-term oral administration contributed to the effect of a range of cytostatic therapeutic dosage rather than adversely affected it."( [Growth dynamics of transplantable murine tumors in the course of dicarbamin-protected chemotherapy].
Nebol'sin, VE; Sedakova, LA; Sitdikova, SM; Treshchalina, EM, 2010)		0.36
" Dose-response curves were constructed, and drug interaction was assessed by the Combination Index (CI) method."( Dasatinib (BMS-35482) has synergistic activity with paclitaxel and carboplatin in ovarian cancer cells.
Adams, DJ; Ayeni, TA; Barry, WT; Berchuck, A; Grace, L; Murphy, SK; Rubatt, JM; Secord, AA; Starr, MD; Teoh, D, 2011)		0.37
"Random assignment was between RT and one infusion of carboplatin dosed at 7 × (glomerular filtration rate + 25) on the basis of EDTA (n = 357) and 90% of this dose if determined on the basis of creatinine clearance (n = 202)."( Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214).
Aass, N; Coleman, R; Gabe, R; Joffe, JK; Mead, GM; Oliver, RT; Pollock, P; Rustin, GJ; Stenning, SP, 2011)		0.37
"Single or combination chemotherapy with paclitaxel, docetaxel, carboplatin, and trastuzumab was administered to 9 baboons at a mean (SD) gestational age of 117 (26) days (paclitaxel, 100 mg/m2 [n = 2]; docetaxel, 100 mg/m2 [n = 2]; paclitaxel, 175 mg/m2 with carboplatin, area under the curve of 6 at standard dosage [n = 2] and 50% dosage [n = 1]; docetaxel, 75 mg/m2 with carboplatin, area under the curve 6 [n = 1]; and docetaxel, 75 mg/m2 with trastuzumab, 8 mg/kg [n = 1])."( Transplacental transfer of paclitaxel, docetaxel, carboplatin, and trastuzumab in a baboon model.
Amant, F; Beijnen, J; Calsteren, KV; Chai, DC; de Bruijn, E; De Catte, L; de Hoon, J; Demarsin, S; Devlieger, R; Heyns, L; Van Bree, R; Verbesselt, R, 2010)		0.36
" Drug dosage was determined by age and angioanatomy."( Intra-arterial chemotherapy for the management of retinoblastoma: four-year experience.
Abramson, DH; Brodie, SE; Dunkel, IJ; Gobin, YP; Marr, BP, 2011)		0.37
"Carboplatin dosing in children is based on renal function and there exists a wealth of formulae available for calculating the body surface area (BSA), the glomerular filtration rate (GFR), and the carboplatin dose."( Carboplatin dosing in children: calculation by different formulae.
Boos, J; Gerss, J; Krefeld, B; Würthwein, G, 2011)		0.37
" Sensory NCI-CTC scores were higher in patients receiving higher cumulative chemotherapy dosage (z = -2."( The validity of neuropathy and neuropathic pain measures in patients with cancer receiving taxanes and platinums.
Beck, SL; Cohen, JA; Lavoie Smith, EM; Pett, MA, 2011)		0.37
"0% of the planned theoretical dosage of carboplatin and 58% of patients received more than 85."( Toxicity profile and adherence to the pharmacotherapeutic regimen of gemcitabine-carboplatin in non-small cell lung cancer.
Albert Marí, A; Boquera Ferrer, ML; Gómez Herrero, D; Merino Sanjuán, M; Víctor Jiménez Torres, N, )		0.13
" TEC chemotherapy (paclitaxel, epirubicin, and carboplatin) has been suggested to have less toxicity; however, the optimal dosage has yet to be determined."( Chemotherapy for endometrial carcinoma (GOGO-EM1 study): TEC (paclitaxel, epirubicin, and carboplatin) is an effective remission-induction and adjuvant therapy.
Asada, M; Egawa-Takata, T; Enomoto, T; Fujita, M; Ito, K; Kimura, T; Kuragaki, C; Miyake, T; Miyatake, T; Morishige, K; Nagamatsu, M; Nakashima, R; Nishio, Y; Nishizaki, T; Ogita, K; Okazawa, M; Tsutsui, T; Ueda, Y; Wakimoto, A; Yamamoto, T; Yamasaki, M; Yoshino, K, 2011)		0.37
" No significant dose-response relationship was found in terms of LRC."( Sequential or concomitant chemotherapy in limited stage small-cell lung cancer.
Anchisi, S; Bieri, S; Elhfidh, M; Khanfir, K; Matzinger, O; Mirimanoff, RO; Ozsahin, M; Zouhair, A, 2011)		0.37
"Glomerular filtration rate (GFR) is an important factor when considering carboplatin dosage adjustment."( [Clinical evaluation of calculating carboplatin dosage using Japanese equation for estimating GFR for gynecologic cancer].
Chiba, Y; Kajitani, F; Kidera, Y; Moriyama, K; Nakao, M; Nishida, S; Sakano, M; Tsubaki, M; Yamazoe, Y; Yanae, M; Yoshinaga, M, 2011)		0.37
"The PBPK model matched the pharmacokinetics in different dosing regimens in adults."( Physiologically based pharmacokinetic modelling of high- and low-dose etoposide: from adults to children.
Boos, J; Hempel, G; Kersting, G; Lippert, J; Willmann, S; Würthwein, G, 2012)		0.38
"A total of 143 patients were randomly assigned to either erlotinib 150 mg daily orally until disease progression (PD) occurred or to chemotherapy with paclitaxel 200 mg/m(2) intravenously (IV) and carboplatin dosed by creatinine clearance (AUC 6) IV on day 1 intercalated with erlotinib 150 mg orally on days 2 through 15 every 3 weeks for four cycles followed by erlotinib 150 mg orally until PD occurred (CT + erlotinib)."( A randomized, phase II, biomarker-selected study comparing erlotinib to erlotinib intercalated with chemotherapy in first-line therapy for advanced non-small-cell lung cancer.
Bunn, PA; Camidge, DR; Camidge, R; Dziadziuszko, R; Eisen, T; Franklin, WA; Hirsch, FR; Kabbinavar, F; Martins, R; Richardson, F; Richardson, K; Rusk, J; Schnell, FM; Sternberg, DW; Varella-Garcia, M; Wacker, B, 2011)		0.37
"Carboplatin dosing depends on accurate glomerular filtration rate (GFR) estimation."( Very high GFR in cancer patients undergoing chemotherapy: prevalence, carboplatin dosing patterns and chemotherapy toxicity.
Bishnoi, S; Jones, DN; Karapetis, C; Kichenadasse, G; Koczwara, B; Lam, E; Roy, AC; Slavotinek, JP, 2011)		0.37
" Carboplatin dosing patterns in this group of patients vary among treating oncologists and a standardized approach is needed."( Very high GFR in cancer patients undergoing chemotherapy: prevalence, carboplatin dosing patterns and chemotherapy toxicity.
Bishnoi, S; Jones, DN; Karapetis, C; Kichenadasse, G; Koczwara, B; Lam, E; Roy, AC; Slavotinek, JP, 2011)		0.37
" This has potential utility in treatment selection and genotype-based dosing strategies."( Gemcitabine and platinum pathway pharmacogenetics in Asian breast cancer patients.
Cordero, MT; Goh, BC; Lee, SC; Ng, SS; Soong, R; Wang, LZ; Wong, AL; Yap, HL; Yeo, WL; Yong, WP, )		0.13
" Recent interest in PLD/carboplatin combination therapy for patients with platinum-sensitive recurrent ovarian cancer has been stirred from Phase-III trials reporting response rates, progressive-free survival and overall survival similar to other platinum-based combinations, but with a more favorable toxicity profile and convenient dosing schedule."( Use of pegylated liposomal doxorubicin in the management of platinum-sensitive recurrent ovarian cancer: current concepts.
Ahmad, S; Holloway, RW; Rakowski, JA, 2012)		0.38
" The present study indicates that further investigation is needed to determine the best dosing and dosing schedule."( [The clinical effect of combination therapy for oral cancer with S-1, superselective intra-arterial chemotherapy, and radiation therapy].
Fukumoto, S; Higuchi, T; Horinouchi, Y; Uehara, S; Yamamoto, C; Yasumori, K; Yoshida, M; Yoshikawa, H, 2011)		0.37
" Here we developed an electrical cell-substrate impedance sensing system (ECIS) capable of continuously measuring the dosage and time response of human proximal tubular epithelial (HK2) cells exposed to four drugs throughout the experimental period."( Use of cellular electrical impedance sensing to assess in vitro cytotoxicity of anticancer drugs in a human kidney cell nephrotoxicity model.
Cheng, J; Mitchelson, K; Wang, L; Xie, F; Xing, W; Xu, Y, 2012)		0.38
" Of the six patients enrolled in the next and lowest dosing level planned in the study, pazopanib 400 mg plus paclitaxel 175 mg m(-2) plus carboplatin AUC5, two patients also experienced DLTs and the study was terminated."( Open-label feasibility study of pazopanib, carboplatin, and paclitaxel in women with newly diagnosed, untreated, gynaecologic tumours: a phase I/II trial of the AGO study group.
Curtis, LB; du Bois, A; Harter, P; Mitrica, I; Ray-Coquard, I; Vergote, I; Wimberger, P, 2012)		0.38
"Although the recommended dosage is restricted to a lower level compared to younger patients, combination therapy using CBDCA with GEM is tolerable and promising for elderly patients with advanced NSCLC."( A phase I/II study of carboplatin plus gemcitabine for elderly patients with advanced non-small cell lung cancer: West Japan Thoracic Oncology Group Trial (WJTOG) 2905.
Aoki, T; Fukuoka, M; Hirashima, T; Ikeda, N; Ishiguro, T; Iwamoto, Y; Kawaguchi, T; Kotani, Y; Kurata, T; Nakagawa, K; Sawa, T; Tsuboi, M, 2012)		0.38
" Belinostat was dosed at 1000 mg/m(2) daily for five days with carboplatin AUC 5 on day three of 21-day cycles."( A phase II evaluation of belinostat and carboplatin in the treatment of recurrent or persistent platinum-resistant ovarian, fallopian tube, or primary peritoneal carcinoma: a Gynecologic Oncology Group study.
Blessing, JA; Disilvestro, PA; Dizon, DS; Drake, RD; Fader, AN; Johnston, CM; Penson, RT; Walker, JL, 2012)		0.38
"The determination of appropriate dosing regimens for the treatment of infants and very young children with cancer represents a major challenge in paediatric oncology."( Chemotherapy in newborns and preterm babies.
Boddy, AV; Veal, GJ, 2012)		0.38
"At the moment there is no evidence from individual studies in children with osteosarcoma and hepatoblastoma treated with different platinum analogues and dosage schedules which underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment."( Medical interventions for the prevention of platinum-induced hearing loss in children with cancer.
van As, JW; van Dalen, EC; van den Berg, H, 2012)		0.38
" Pharmacokinetic studies of BIIB036 in tumor-bearing mice revealed a half-life of approximately three days suggesting twice a week dosing would be necessary to maintain efficacy."( The anti-Fn14 antibody BIIB036 inhibits tumor growth in xenografts and patient derived primary tumor models and enhances efficacy of chemotherapeutic agents in multiple xenograft models.
Joseph, IB; Kelly, R; Michaelson, JS; Wortham, K; Yang, L; Zhang, X, 2012)		0.38
" The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m(-2) (range, 150-300 mg m(-2)) and 4 (range, 2-11), respectively."( Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision.
Dank, G; Garrett, LD; Kitchell, BE; Kleiter, M; Northrup, N; Post, GS; Rassnick, KM; Segev, G; Sellon, RK; Sokolovsky, Y, 2014)		0.4
" Other toxicities in all cycles included neutropenia (95% grade 3-4; 91% in the 150 mg dosing cohort), thrombocytopenia (35% grade 3-4), and fatigue (10% grade 3)."( A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer.
Barry, WT; Berchuck, A; Broadwater, G; Havrilesky, LJ; Lancaster, J; Lee, PS; Secord, AA; Teoh, DK; Wenham, RM; Yu, M, 2012)		0.38
" On the basis of our results we recommend that the rGFR should be used for accurate carboplatin chemotherapy dosing and where unavailable the use of the CG equation is preferred."( Overestimation of carboplatin doses is avoided by radionuclide GFR measurement.
Britten, A; Craig, AJ; Heenan, SD; Irwin, AG; Samol, J, 2012)		0.38
" However, optimal dosing schedule, including drug selection, number of cycles, and interval between chemotherapy and cystectomy, as well as acceptable regimens remain to be established."( Efficacies and safety of neoadjuvant gemcitabine plus carboplatin followed by immediate cystectomy in patients with muscle-invasive bladder cancer, including those unfit for cisplatin: a prospective single-arm study.
Hashimoto, Y; Hatakeyama, S; Kamimura, N; Koie, T; Ohyama, C; Yamamoto, H; Yoneyama, T, 2013)		0.39
" It was designed to maximize cytoreduction via high dosing of synergistically interacting agents, while minimizing morbidity in patients with resistant neuroblastoma (NB) and ineligible for clinical trials due to myelosuppression from previous therapy."( 5-day/5-drug myeloablative outpatient regimen for resistant neuroblastoma.
Basu, EM; Cheung, NK; Kramer, K; Kushner, BH; Modak, S; Roberts, SS, 2013)		0.39
" DCP showed favourable bioavailability and stability in vivo, and the recommended Phase II dosage for DCP-containing chemotherapy is 450 mg/m(2)."( Phase I clinical trial of the novel platin complex dicycloplatin: clinical and pharmacokinetic results.
Guan, ZZ; Guo, Y; Huang, H; Jiang, WQ; Li, S; Liao, H; Yang, XQ; Zhan, J; Zou, BY, 2013)		0.39
"Carboplatin dosing using the Calvert and Cockcroft-Gault formulae in patients with low serum creatinine levels is discussed controversially."( Carboplatin dose calculation in lung cancer patients with low serum creatinine concentrations using CKD-EPI and Cockcroft-Gault with different weight descriptors.
Kaag, D, 2013)		0.39
"The results show that application of the alternate size descriptor adjusted body weight in the Cockcroft-Gault equation can improve dosing accuracy especially in overweight and obese patients with low serum creatinine levels."( Carboplatin dose calculation in lung cancer patients with low serum creatinine concentrations using CKD-EPI and Cockcroft-Gault with different weight descriptors.
Kaag, D, 2013)		0.39
"A phase I dose escalation study was performed to determine the maximum tolerated dose (MTD) of intercalated dosing of BMS-690514, a reversible oral panHER/VEGF receptor inhibitor, combined with paclitaxel/carboplatin (PC) in advanced solid tumors."( A phase I trial to determine the safety, pharmacokinetics, and pharmacodynamics of intercalated BMS-690514 with paclitaxel/carboplatin (PC) in advanced or metastatic solid malignancies.
Adjei, AA; Belani, CP; Chow, LQ; Dy, GK; Fortin, C; Gupta, A; Jonker, DI; Laurie, SA; Nicholas, G; Park, JS; Patricia, D; Sbar, EI; Zhang, S, 2013)		0.39
"Although pulmonary dosing of large porous particles has been shown to sustain drug delivery for a few days, there are no reports on safety or long term delivery."( Supercritical fluid technology based large porous celecoxib-PLGA microparticles do not induce pulmonary fibrosis and sustain drug delivery and efficacy for several weeks following a single dose.
Dhanda, DS; Kompella, UB; Mirvish, SS; Tyagi, P, 2013)		0.39
"Two-Gy daily RT to a total dosage of 70 Gy was well tolerated with similar survival to 45 Gy (1."( A pooled analysis of limited-stage small-cell lung cancer patients treated with induction chemotherapy followed by concurrent platinum-based chemotherapy and 70 Gy daily radiotherapy: CALGB 30904.
Blackstock, AW; Bogart, JA; Crawford, J; Hodgson, L; Pang, H; Salama, JK; Schild, SE; Urbanic, JJ; Vokes, EE, 2013)		0.39
" Although several unanswered questions remain, such as the optimal dosage and duration of treatment, current evidence suggests that bevacizumab combination therapy extends the treatment options available for patients with ovarian cancer."( Bevacizumab combination therapy: a review of its use in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer.
Dhillon, S, 2013)		0.39
" More research is needed, and efforts should be made to have a universal modified Calvert formula with standardized assumptions to achieve consistent dosing across practices."( Survey of carboplatin dosing strategies in oncology practices.
Blankenship, P; Waddell, JA, )		0.13
" The magnitude of synergy depended on the treatment sequence; a schedule of MK-2206 dosed before or concurrently with chemotherapy was not as effective as being dosed after chemotherapy."( MK-2206, an Akt inhibitor, enhances carboplatinum/paclitaxel efficacy in gastric cancer cell lines.
Almhanna, K; Cubitt, CL; Husain, K; Kazim, S; Malafa, M; Sebti, S; Sullivan, D; Zhang, S, 2013)		0.39
"All bedside formulae provide similar levels of concordance in dosage selection for the renal excreted chemotherapy drugs when compared with the use of a direct measure of renal function."( Dosing of cytotoxic chemotherapy: impact of renal function estimates on dose.
Dooley, MJ; Poole, SG; Rischin, D, 2013)		0.39
"In this phase I dose-escalation study, patients received oral sunitinib on a continuous daily dosing (CDD) schedule (37."( Sunitinib combined with pemetrexed and carboplatin in patients with advanced solid malignancies--results of a phase I dose-escalation study.
Blais, N; Camidge, DR; Chao, RC; Chow, LQ; Diab, SG; Jonker, DJ; Laurie, SA; Ruiz-Garcia, A; Soulières, D; Thall, A; Zhang, K, 2013)		0.39
" Carboplatin is a second-generation, nonnephrotoxic platinum analog that can be hemodialyzed, although no formal guidelines are available regarding the dosing for patients receiving hemodialysis."( Carboplatin pharmacokinetics in a patient receiving hemodialysis.
Fetterly, GJ; Fong, MK; Iyer, RV; McDougald, LJ, 2014)		0.4
" These results suggest there is a dosage window for actions of epimorphin on cellular differentiation, wherein it can either suppress or enhance epithelial differentiation of OCCs."( Epimorphin-induced MET sensitizes ovarian cancer cells to platinum.
Crow, J; Godwin, AK; Hirst, J; Pessetto, Z; Pressetto, Z; Yew, KH, 2013)		0.39
" Algebraic expressions are established for describing the time history of the concentrations, and formulas for dose and dosing interval are determined so as to ensure the requirement on concentrations."( Scaling adult dose and schedule of anticancer agents to children.
Dawson, TH, 2013)		0.39
" Basic aspects of the theory are confirmed for dose and dosing interval of adult and 4-year-old child."( Scaling adult dose and schedule of anticancer agents to children.
Dawson, TH, 2013)		0.39
" Paclitaxel was administered at 175 mg/m2, and the carboplatin dosage was calculated by the Calvert formula."( [A patient with recurrent ovarian clear cell adenocarcinoma and chronic kidney disease exhibited complete response to paclitaxel plus carboplatin].
Kamura, T; Muto, M; Nishio, S; Ota, S; Sonoda, G; Takemoto, S; Ushijima, K, 2013)		0.39
" Because the estimated glomerular filtration rate, and therefore the carboplatin dose, is based on the serum creatinine level, dosing of carboplatin for amputees is a challenge."( Dosing of carboplatin in a patient with amputated legs: A case report.
Brouwers, EE; Huitema, AD; Kuck, EM; Rozemeijer, R; van Gorp, F; van Rens, MT, 2014)		0.4
" Intrinsic resistance due to pre-existing cohorts of resistant cells precludes tumor regression, but dosing strategies that extend disease-free survival periods can still be identified."( Exploiting the synergy between carboplatin and ABT-737 in the treatment of ovarian carcinomas.
Byrne, HM; Jain, HV; Meyer-Hermann, M; Richardson, A, 2014)		0.4
"Single cycle carboplatin, dosed by glomerular filtration rate (GFR), is standard adjuvant therapy for stage 1 seminoma."( Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma.
Forte, C; Gillen, G; Macpherson, IR; Mark, PB; Morrison, P; Shepherd, ST; White, JD, 2014)		0.4
"Our data support further evaluation of the CKD-EPI formula in this patient population but clinically significant variances in carboplatin dosing occur using non-isotopic methods of GFR estimation."( Performance of formulae based estimates of glomerular filtration rate for carboplatin dosing in stage 1 seminoma.
Forte, C; Gillen, G; Macpherson, IR; Mark, PB; Morrison, P; Shepherd, ST; White, JD, 2014)		0.4
" The precision of carboplatin dosage based on eGFR was calculated."( Reliability of estimated glomerular filtration rate in patients treated with platinum containing therapy.
Daugaard, G; Feldt-Rasmussen, B; Gundgaard, MG; Lauritsen, J; Mortensen, MS; Oturai, PS, 2014)		0.4
" This very small dosage of steroid was hardly supposed to weaken his immune system, but rather potentially led to an inappropriate supplementation of his adrenal function, assuming that the serum sodium and chlorine levels decreased."( Fatal Candida septic shock during systemic chemotherapy in lung cancer patient receiving corticosteroid replacement therapy for hypopituitarism: a case report.
Hotta, K; Iwaki, N; Kiura, K; Kubo, T; Minami, D; Morichika, D; Sato-Hisamoto, A; Takata, K; Tanimoto, M; Uchida, K, 2014)		0.4
"The objective of this study was to determine a dosing schedule of neoadjuvant chemotherapy using carboplatin, paclitaxel, and bevacizumab in women with advanced ovarian cancer, evaluating feasibility and outcomes from interval cytoreductive surgery (ICS)."( Feasibility of interval cytoreduction following neoadjuvant chemotherapy with carboplatin, weekly paclitaxel, and bevacizumab for advanced ovarian cancer--a phase 1 study.
Backes, FJ; Cohn, DE; Copeland, LJ; Eisenhauer, EL; Fowler, JM; O'Malley, DM; Salani, R, 2014)		0.4
" The primary objective was to determine a feasible dosing schedule."( Feasibility of interval cytoreduction following neoadjuvant chemotherapy with carboplatin, weekly paclitaxel, and bevacizumab for advanced ovarian cancer--a phase 1 study.
Backes, FJ; Cohn, DE; Copeland, LJ; Eisenhauer, EL; Fowler, JM; O'Malley, DM; Salani, R, 2014)		0.4
" Underdosing of carboplatin by 10% has been shown to almost double the rate of relapse and hence correct dosing based on accurate GFR measurement is crucial."( Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.
Cathomas, R; Ellis, S; Fehr, M; Geldart, TR; Klingbiel, D; Mead, GM; Nagaraj, N; Simmonds, P; von Moos, R; Wheater, M, 2014)		0.4
" All patients had serum creatinine measured and underwent GFR measurement with a radioisotope ((51)Cr EDTA or (99m)Tc DTPA), which was compared with seven standard GFR estimation formulae (Cockcroft-Gault, CKD-EPI, Jelliffe, Martin, Mayo, MDRD, Wright) and a flat dosing strategy."( Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.
Cathomas, R; Ellis, S; Fehr, M; Geldart, TR; Klingbiel, D; Mead, GM; Nagaraj, N; Simmonds, P; von Moos, R; Wheater, M, 2014)		0.4
" The flat dosing strategy, Wright and Cockcroft-Gault formulae, showed the smallest bias with mean percentage error of +1."( Relevant risk of carboplatin underdosing in cancer patients with normal renal function using estimated GFR: lessons from a stage I seminoma cohort.
Cathomas, R; Ellis, S; Fehr, M; Geldart, TR; Klingbiel, D; Mead, GM; Nagaraj, N; Simmonds, P; von Moos, R; Wheater, M, 2014)		0.4
" To describe chemotherapy dosing practices in normal, overweight and obese patients treated for FIGO Stage III/IV serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS)."( Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS).
Au-Yeung, G; Bressel, M; DeFazio, A; Fereday, S; Mileshkin, L; Webb, PM, 2014)		0.4
"Obesity is common in ovarian cancer patients, and commonly results in lower chemotherapy dosing than recommended."( Impact of obesity on chemotherapy dosing for women with advanced stage serous ovarian cancer in the Australian Ovarian Cancer Study (AOCS).
Au-Yeung, G; Bressel, M; DeFazio, A; Fereday, S; Mileshkin, L; Webb, PM, 2014)		0.4
"The Calvert equation has been extensively used to determine the dosage of carboplatin."( Dose adjustment of carboplatin in patients on peritoneal dialysis.
Guddati, AK; Joy, PS; Marak, CP, 2014)		0.4
"PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible."( NMR cryoporometry characterisation studies of the relation between drug release profile and pore structural evolution of polymeric nanoparticles.
Edler, KJ; Gopinathan, N; Lowe, JP; Rigby, SP; Yang, B, 2014)		0.4
" The degree to which biweekly dosing may present a more rationale schedule for this triplet should be evaluated further."( A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer.
Callahan, MJ; Cobb, B; Cohn, DE; Copeland, LJ; Eisenhauer, EL; Fowler, JM; O'Malley, DM; Salani, R; Sutton, G; Zanagnolo, V, 2014)		0.4
"At the moment there is no evidence from individual studies in children with osteosarcoma or hepatoblastoma treated with different platinum analogues and dosage schedules which underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment."( Medical interventions for the prevention of platinum-induced hearing loss in children with cancer.
van As, JW; van Dalen, EC; van den Berg, H, 2014)		0.4
" Liposome-paclitaxel was injected on D1 at a dosage of 175 mg/m(2); the same dose and administration with paclitaxel injection in the PC group for a maximum of 2 cycles."( Comparison of efficacy and safety between liposome-paclitaxel injection plus carboplatin and paclitaxel plus carboplatin as first line treatment in advanced non-small cell lung cancer.
Wang, HY; Zhang, XR, 2014)		0.4
" There are multiple age-specific differences in renal and hepatic function that explain the need for higher dosing in pediatric patients without increasing the risk of toxicity."( Choroid plexus papilloma-A case highlighting the challenges of extrapolating pediatric chemotherapy regimens to adult populations.
Barman, SL; Dinsfriend, WM; Gerber, DE; Jean, GW, 2016)		0.43
" Because the clearance of carboplatin strongly correlates with the glomerular filtration rate (GFR), its dosage is calculated with the Calvert formula on the basis of the patient's GFR to achieve the target area under the plasma drug concentration-time curve (AUC) for each patient."( Carboplatin dosing for adult Japanese patients.
Ando, Y; Hasegawa, Y; Shimokata, T; Yasuda, Y, 2014)		0.4
"Accurate glomerular filtration rate (GFR) evaluation is significant for drug dosing of carboplatin, anticancer drug excreted mainly from kidney."( Renal function evaluation in patients with cancer who were scheduled to receive carboplatin or S-1.
Ando, Y; Hayashi, M; Kamiya, H; Kobayashi, R; Maruyama, S; Matsuo, S; Nakao, M; Shibata, K; Shimokata, T; Teramachi, H; Tsuchiya, T; Yasuda, Y, 2015)		0.42
" Subjects were 41 patients with cancer whose GFR values were measured by Cin for drug dosing studies of carboplatin or S-1 in Nagoya University Hospital from 2007 to 2010 and 29 non-cancer patients."( Renal function evaluation in patients with cancer who were scheduled to receive carboplatin or S-1.
Ando, Y; Hayashi, M; Kamiya, H; Kobayashi, R; Maruyama, S; Matsuo, S; Nakao, M; Shibata, K; Shimokata, T; Teramachi, H; Tsuchiya, T; Yasuda, Y, 2015)		0.42
" Surgical resection was performed, and administration of carboplatin was scheduled postoperatively aiming at 5 mg·min/mL of the area under the curve from the time of dosing to the time of the last observation (AUC(0-t))."( Pharmacokinetics of Carboplatin in a One-Year-Old Anuric Boy Undergoing Hemodialysis and a Review of the Literature.
Ishikawa, T; Ito, S; Kamei, K; Kiyotani, C; Mori, T; Nakamura, H; Ogura, M; Sako, M; Sato, M; Tanaka, H; Uno, T, 2015)		0.42
" MSA-eCrCl was used to simulate carboplatin dosing in a retrospective series of advanced non-small cell lung cancer (NSCLC)."( Development of a new equation to estimate creatinine clearance in cancer patients.
Baracos, VE; Butts, C; Chu, MP; Damaraju, VL; Hanson, J; Kuzma, M; McCaw, L; Sawyer, MB; Stretch, C, 2015)		0.42
"0 on day 1) every 3 weeks, with 3-6 patients treated at each irinotecan dosage level (levels I-IV)."( Weekly irinotecan combined with carboplatin for patients with small-cell lung cancer: A phase I study.
Inoue, A; Ishimoto, O; Maemondo, M; Nukiwa, T; Sugawara, S, 2015)		0.42
" The first dose level (DL A) tested vorinostat as daily oral dosing from days 1 to 14."( Phase I study of combination of vorinostat, carboplatin, and gemcitabine in women with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or peritoneal cancer.
Berlin, S; Campos, S; Horowitz, N; Krasner, C; Lee, H; Liu, J; Matulonis, U; Obermayer, E; Penson, R; Whalen, C, 2015)		0.42
" All enrolled patients received adjuvant chemotherapy every 3 weeks according to the scheme carboplatin, dosed at an area under the curve of 6, and paclitaxel 175 mg/mq given every 3 weeks for at least 3 cycles."( Chemotherapy as Adjuvant Treatment for Intermediate-High Risk Early-Stage Endometrial Cancer: A Pilot Study.
Aloisi, A; Angioli, R; Capriglione, S; De Cicco Nardone, C; Laraud, F; Miranda, A; Montera, R; Plotti, F; Scaletta, G; Terranova, C, 2015)		0.42
" Despite this, literature reports regarding dosing strategies and pharmacokinetic behaviour of chemotherapeutics in avian species are lacking."( Comparative Pharmacokinetics and Allometric Scaling of Carboplatin in Different Avian Species.
Antonissen, G; Croubels, S; De Backer, P; De Baere, S; Devreese, M; Hellebuyck, T; Martel, A; Rouffaer, L; Stemkens, HJ; Van de Maele, I, 2015)		0.42
"AUC values achieved were within 15% of target values for the individual courses of treatment in all but one patient (12/13 courses of treatment), with dose modifications of up to 215% required to achieve target AUC values, based on initial mg/kg dosing schedules."( Carboplatin therapeutic monitoring in preterm and full-term neonates.
Dommett, RM; Errington, J; Hayden, J; Hobin, D; Jenkinson, H; Murphy, D; Picton, S; Tweddle, DA; Veal, GJ, 2015)		0.42
" In the absence of therapeutic drug monitoring, body-weight based dosing is recommended, with dosing guidance provided for both approaches to inform future treatment."( Carboplatin therapeutic monitoring in preterm and full-term neonates.
Dommett, RM; Errington, J; Hayden, J; Hobin, D; Jenkinson, H; Murphy, D; Picton, S; Tweddle, DA; Veal, GJ, 2015)		0.42
" Regarding concomitant chemoradiotherapy (CRT), studies focused on the dosage and sequence of cisplatin administration are currently particularly featured."( [The most important study results concerning nonsurgical primary treatment of locally advanced head and neck cancer: Highlights of the ASCO Meeting 2015].
Busch, CJ; Gliese, A; Knecht, R, 2015)		0.42
" Eligible patients were randomized to one of the following treatment arms: PCG, P 175 mg/m(2), and C AUC 5 administered intravenously on day 1 intercalated with G 250 mg orally on days 2 through 15 every 3 weeks for four cycles followed by G 250 mg orally until progressive disease; or PC, same dosing schedule for four cycles only."( Randomized phase II study of paclitaxel/carboplatin intercalated with gefitinib compared to paclitaxel/carboplatin alone for chemotherapy-naïve non-small cell lung cancer in a clinically selected population excluding patients with non-smoking adenocarcino
Ahn, JH; Choi, CM; Choi, YJ; Kim, SW; Lee, DH; Lee, JS; Lee, SJ, 2015)		0.42
" Using an intermittent dosing schedule of combined carboplatin and Nutlin-3a, there was a significant reduction in primary tumor growth and lung metastases compared with vehicle and single-agent treatments."( Potentiation of Carboplatin-Mediated DNA Damage by the Mdm2 Modulator Nutlin-3a in a Humanized Orthotopic Breast-to-Lung Metastatic Model.
Bailey, BJ; Batuello, CN; Ding, J; Eischen, CM; Georgiadis, TM; Gunter, TZ; Hanenberg, H; Long, EC; Marchal, CC; Mayo, LD; Minto, RE; Peterman, KM; Pollok, KE; Saadatzadeh, MR; Safa, AR; Sandusky, GE; Shannon, HE; Silver, JM; Sinn, AL; Spragins, TK; Sprouse, AA; Territo, PR; Tonsing-Carter, E; Wang, H, 2015)		0.42
" for both dosing arms), myelosuppression was the DLT."( A phase I trial of pegylated liposomal doxorubicin (PLD), carboplatin, bevacizumab and veliparib in recurrent, platinum-sensitive ovarian, primary peritoneal, and fallopian tube cancer: An NRG Oncology/Gynecologic Oncology Group study.
Armstrong, DK; Brady, WE; DiSilvestro, PA; Fracasso, PM; Landrum, LM; Moore, KN; O'Malley, DM; Rose, PG; Tenney, ME, 2016)		0.43
" Of these patients, 310 received atezolizumab treatment (five enrolled patients later did not meet eligibility criteria and were not dosed with study drug)."( Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial.
Abidoye, O; Bajorin, D; Balar, AV; Balmanoukian, A; Bellmunt, J; Bourgon, R; Burris, HA; Canil, C; Castellano, D; Cui, N; Dawson, N; Dreicer, R; Fine, GD; Fleming, MT; Frampton, GM; Galsky, MD; Grivas, P; Hoffman-Censits, J; Joseph, RW; Loriot, Y; Mariathasan, S; Necchi, A; Nickles, D; O'Donnell, PH; Perez-Gracia, JL; Petrylak, DP; Powles, T; Retz, MM; Rosenberg, JE; Srinivas, S; van der Heijden, MS, 2016)		0.43
" Patients received once-daily vandetanib (planned dosing levels of 100, 200, and 300 mg) with concomitant daily radiotherapy (1."( Induction Therapy for Locally Advanced, Resectable Esophagogastric Cancer: A Phase I Trial of Vandetanib (ZD6474), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiotherapy Followed by Resection.
Astsaturov, IA; Berger, AC; Boland, PM; Burtness, BA; Cheng, JD; Cohen, SJ; Cooper, HS; Davey, M; Lebenthal, A; Meyer, JE; Neuman, T; Olszanski, AJ; Scott, WJ, 2017)		0.46
"When using area under the concentration-time curve-based strategies for dosing carboplatin, accurate estimation of glomerular filtration rate is required for determining dose."( Impact of Isotope Dilution Mass Spectrometry (IDMS) Standardization on Carboplatin Dose and Adverse Events.
Donald Harvey, R; Lawson, J; McKibbin, T; Switchenko, JM, 2016)		0.43
"Carboplatin dosing based on real weight in obese patients resulted in increased hematologic toxicity, mainly thrombocytopenia."( Hematological toxicity of carboplatin for gynecological cancer according to body mass index.
Batista, N; Gonzalez-de-la-Fuente, GA; Gutierrez, F; Nazco, GJ; Oramas, J, 2016)		0.43
"The extrapolation of the Calvert formula has utility in calculating the CBDCA dosage for DeVIC ± R therapy, and therapeutic efficacy was increased by maintaining the AUC of CBDCA at ≥4."( Evaluation of a method for calculating carboplatin dosage in DeVIC ± R therapy (combination therapy of dexamethasone, etoposide, ifosfamide and carboplatin with or without rituximab) as a salvage therapy in patients with relapsed or refractory non-Hodgkin
Ando, M; Ando, Y; Emi, N; Hayashi, T; Inaguma, Y; Ito, K; Okamoto, A; Okamoto, M; Tomono, A; Tsuge, M; Yamada, S, 2016)		0.43
" The National Institute for Health and Care Excellence's (NICE's) recent decision not to recommend bevacizumab for advanced ovarian cancer was not based on evidence related to the unlicensed lower dosage (7."( The Cost-Effectiveness of Bevacizumab in Advanced Ovarian Cancer Using Evidence from the ICON7 Trial.
Cook, A; Embleton, A; Epstein, D; Hinde, S; Perren, T; Sculpher, M, 2016)		0.43
"The American Society of Clinical Oncology provides clinical practice guidelines for appropriate cytotoxic chemotherapy dosing for obese adult patients with cancer."( Myelosuppression by chemotherapy in obese patients with gynecological cancers.
Kamimura, K; Matsumoto, Y; Moriyama, M; Saijo, Y; Zhou, Q, 2016)		0.43
" This study was initiated to validate pharmacokinetically (PK)-guided paclitaxel dosing in patients with advanced non-small-cell lung cancer (NSCLC) to avoid supra- or subtherapeutic exposure."( Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).
Behringer, DM; Eberhardt, W; Fischer, JR; Gauler, TC; Henrich, A; Hilger, RA; Jaehde, U; Joerger, M; Kimmich, M; Kloft, C; Ko, YD; Kopp, HG; Kraff, S; Mayer, F; Miller, MC; Moritz, B; Mueller, L; Reck, M; Reinmuth, N; Roessler, M; Salamone, SJ; von Pawel, J, 2016)		0.43
"Patients with newly diagnosed, advanced NSCLC were randomly assigned to receive up to 6 cycles of 3-weekly carboplatin AUC 6 or cisplatin 80 mg/m(2) either with standard paclitaxel at 200 mg/m(2) (arm A) or PK-guided dosing of paclitaxel (arm B)."( Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).
Behringer, DM; Eberhardt, W; Fischer, JR; Gauler, TC; Henrich, A; Hilger, RA; Jaehde, U; Joerger, M; Kimmich, M; Kloft, C; Ko, YD; Kopp, HG; Kraff, S; Mayer, F; Miller, MC; Moritz, B; Mueller, L; Reck, M; Reinmuth, N; Roessler, M; Salamone, SJ; von Pawel, J, 2016)		0.43
"PK-guided dosing of paclitaxel does not improve severe neutropenia, but reduces paclitaxel-associated neuropathy and thereby improves the benefit-risk profile in patients with advanced NSCLC."( Open-label, randomized study of individualized, pharmacokinetically (PK)-guided dosing of paclitaxel combined with carboplatin or cisplatin in patients with advanced non-small-cell lung cancer (NSCLC).
Behringer, DM; Eberhardt, W; Fischer, JR; Gauler, TC; Henrich, A; Hilger, RA; Jaehde, U; Joerger, M; Kimmich, M; Kloft, C; Ko, YD; Kopp, HG; Kraff, S; Mayer, F; Miller, MC; Moritz, B; Mueller, L; Reck, M; Reinmuth, N; Roessler, M; Salamone, SJ; von Pawel, J, 2016)		0.43
"We evaluated racial/ethnic differences in chemotherapy dosing and survival in a cohort study among members of Kaiser Permanente Northern California, and thus with equivalent access to health care."( Racial/Ethnic Disparities in Ovarian Cancer Treatment and Survival.
Bandera, EV; Kushi, LH; Lee, VS; Powell, CB; Rodriguez-Rodriguez, L, 2016)		0.43
"Patients ≥70years were treated less often with concurrent cisplatin dosed every 3weeks (25."( Increased acute mortality with chemoradiotherapy for locally advanced head and neck cancer in patients ≥70years.
Caudell, JJ; Harrison, LB; Kish, JA; McCaffrey, J; Naghavi, AO; Otto, KJ; Russell, J; Strom, TJ; Trotti, AM, 2017)		0.46
" This hinders robust estimates of dose-response associations and, hence, optimal normal tissue-sparing strategies from being elucidated."( Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy.
Apte, A; Bhide, SA; Dean, JA; Deasy, JO; Gay, H; Gulliford, SL; Harrington, KJ; Jones, AB; Newbold, KL; Nutting, CM; Oh, JH; Schick, U; Welsh, LC; Wong, KH, 2016)		0.43
"FPLS and functional principal component analysis marginally improved predictive performance compared with PLR and provided robust dose-response associations."( Functional Data Analysis Applied to Modeling of Severe Acute Mucositis and Dysphagia Resulting From Head and Neck Radiation Therapy.
Apte, A; Bhide, SA; Dean, JA; Deasy, JO; Gay, H; Gulliford, SL; Harrington, KJ; Jones, AB; Newbold, KL; Nutting, CM; Oh, JH; Schick, U; Welsh, LC; Wong, KH, 2016)		0.43
"Among the adjuvant options to be proposed to patients with stage I seminoma after orchiectomy, the administration of a single cycle of carboplatin, at the dosage reaching an area under the curve of 7 mg/mL/min (AUC7), is a relatively recent introduction in clinical practice."( Use of AUC7 adjuvant carboplatin in patients with stage I seminoma: systematic review of the literature.
Artibani, W; Cerruto, MA; Diminutto, A; Porcaro, AB; Siracusano, S, )		0.13
" Pegylated liposomal doxorubicin was dosed at 40 mg/M every 28 days except in 7 patients (5 received PLD dosed at 30 mg/M in combination with carboplatin and 2 received PLD dosed at 20 mg/M, one of which was in combination with etoposide)."( Efficacy of Pegylated Liposomal Doxorubicin in Low-Grade Serous Ovarian Carcinoma.
Adbul-Karim, F; Link, N; Michener, CM; Radeva, M; Rose, PG, 2017)		0.46
" Twelve patients received weekly dosing at 60 to 100 mg/m²."( Universal tolerance of nab-paclitaxel for gynecologic malignancies in patients with prior taxane hypersensitivity reactions.
Mahdi, H; Maurer, K; Michener, C; Rose, PG, 2017)		0.46
"Monitoring renal function is critical in treating pediatric patients, especially when dosing nephrotoxic agents."( Derivation of new equations to estimate glomerular filtration rate in pediatric oncology patients.
Brennan, RC; Cross, SJ; Daryani, VM; Gregornik, D; Millisor, VE; Molinelli, A; Pauley, JL; Roberts, JK; Stewart, CF; Sun, Y; Tang, L; Ward, D, 2017)		0.46
" The next cohort was changed to a predefined alternate dosing schedule (days 1-5 and 8-12)."( Phase I study of oral ridaforolimus in combination with paclitaxel and carboplatin in patients with solid tumor cancers.
Apte, SM; Chon, HS; Kang, S; Lee, JK; Shahzad, MM; Wenham, RM; Williams-Elson, I, 2017)		0.46
" The guide was evaluated using timed simulated chemotherapy orders pre- and post-education consisting of a general chemotherapy order and a carboplatin dosing order."( Creation and evaluation of a cancer chemotherapy order review guide for use at a community hospital.
Punke, AP; Waddell, JA, 2019)		0.51
" Ribavirin dosing was weight based."( Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus-associated oropharyngeal squamous cell cancer.
Dunn, LA; Fury, MG; Haque, SS; Ho, AA; Katabi, N; Pfister, DG; Sherman, EJ, 2018)		0.48
"This study has identified a truncated dosing regimen and recommended phase II dose of demcizumab (5 mg/kg q3-weekly ×4) for subsequent clinical evaluation in combination with standard carboplatin and pemetrexed chemotherapy."( Phase IB Trial of the Anti-Cancer Stem Cell DLL4-Binding Agent Demcizumab with Pemetrexed and Carboplatin as First-Line Treatment of Metastatic Non-Squamous NSCLC.
Harris, DL; Hidalgo, M; Hughes, BGM; Jameson, MB; Kapoun, AM; Kotasek, D; Markman, B; McKeage, MJ; Millward, MJ; Stagg, RJ; Xu, L, 2018)		0.48
"2 g/m2 and carboplatin AUC 5 dosing schedule."( Gemcitabine and carboplatin in metastatic nonsmall cell lung cancer: Experience from a tertiary cancer center in South India.
Devika, T; Dubashi, B; Kayal, S; Kumar, R; Shewade, DG, )		0.13
"A median of three cycles of divided dose paclitaxel (D1, D11) concurrent with carboplatin dosed every 3 weeks was found to be safe and feasible as adjuvant to surgery in early endometrial and ovarian cancers or as neoadjuvant treatment in chemotherapy-naive women with ovarian cancer."( Carboplatin (every 21 days) and divided-dose paclitaxel (days 1, 11): rationale and tolerance in chemotherapy naïve women with high-grade epithelial cancers of Mullerian origin.
Kudlowitz, D; Muggia, F; Musa, F; Velastegui, A, 2018)		0.48
"To evaluate the current NCI-CTEP recommendation and the clinical use of Calvert Formula-derived carboplatin dosing pattern in the treatment of advanced lung cancer patients and assess carboplatin-related toxicity in relation to the degree of dose fluctuation."( Correlation between different carboplatin dosing patterns and its toxicity analysis in patients with advanced lung cancers: A retrospective study.
Kartolo, A; Robinson, A, 2019)		0.51
" The carboplatin dosing pattern and carboplatin-related toxicity were collected and analysed on SPSS IBM for Windows version 24."( Correlation between different carboplatin dosing patterns and its toxicity analysis in patients with advanced lung cancers: A retrospective study.
Kartolo, A; Robinson, A, 2019)		0.51
" Our study found no significant association between prescribed high-risk dosing fluctuation (>10% increased from initial dose) and carboplatin-related toxicities."( Correlation between different carboplatin dosing patterns and its toxicity analysis in patients with advanced lung cancers: A retrospective study.
Kartolo, A; Robinson, A, 2019)		0.51
" Only 9% of patients were treated with a fixed dosing pattern (i."( Correlation between different carboplatin dosing patterns and its toxicity analysis in patients with advanced lung cancers: A retrospective study.
Kartolo, A; Robinson, A, 2019)		0.51
" By concurrent administration of carboplatin and olaparib at various molar ratios of drugs, the aim of this study was to explore the optimal dosing ratio of carboplatin-olaparib combinations in a comprehensive panel of eight BRCA-proficient and -deficient high-grade serous ovarian cancer (HGSOC) cell lines."( BRCA Status Does Not Predict Synergism of a Carboplatin and Olaparib Combination in High-Grade Serous Ovarian Cancer Cell Lines.
Allen, C; Evans, JC; Piquette-Miller, M; Shen, YT; Zafarana, G, 2018)		0.48
" In this study, we adjusted the dosage of the triplet regimen and introduced carboplatin in cisplatin-intolerable patients."( Response to Combination Chemotherapy With Paclitaxel/Ifosfamide/Platinum Versus Paclitaxel/Platinum for Patients With Metastatic, Recurrent, or Persistent Carcinoma of the Uterine Cervix: A Retrospective Analysis.
Bae, DS; Choi, CH; Choi, HJ; Kim, BG; Kim, TJ; Lee, JW; Lee, YY; Paik, ES, 2018)		0.48
"Eighteen patients were enrolled and dosed with combination therapy; thirteen continued with mirvetuximab soravtansine maintenance following carboplatin discontinuation."( Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer.
Birrer, MJ; Gonzalez-Martin, A; Malek, K; Martin, LP; Moore, KN; O'Malley, DM; Vergote, I, 2018)		0.48
" This two-drug regimen, with carboplatin dosed using the Calvert formula, yielded convincing noninferior outcomes when compared with the prior, more toxic, regimen of cisplatin/paclitaxel."( Carboplatin/Paclitaxel Induction in Ovarian Cancer: The Finer Points.
Boyd, LR; Muggia, FM, 2018)		0.48
"To describe and analyze the variability in carboplatin dosing strategies in Spanish hospitals."( Variability of carboplatin dose calculation methods in Spain.
Burgos-San José, A; Cajaraville-Ordoñana, G; Cuesta-Grueso, C; Díaz-Carrasco, MS; Mangues-Bafalluy, I; Poquet-Jornet, JE, 2019)		0.51
"We designed a questionnaire consisting of 19 multiple-choice items structured in two sections (hospital characteristics and carboplatin dosing data)."( Variability of carboplatin dose calculation methods in Spain.
Burgos-San José, A; Cajaraville-Ordoñana, G; Cuesta-Grueso, C; Díaz-Carrasco, MS; Mangues-Bafalluy, I; Poquet-Jornet, JE, 2019)		0.51
"Carboplatin dosage is calculated by using the estimated glomerular filtration rate (GFR) to achieve a target plasma area under the plasma concentration-time curve (AUC)."( Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Boddy, AV; Duong, JK; Errington, J; Ladenstein, R; Nath, CE; Shaw, PJ; Veal, GJ, 2019)		0.51
" A population pharmacokinetic model was built for carboplatin to evaluate various dosing formulas."( Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Boddy, AV; Duong, JK; Errington, J; Ladenstein, R; Nath, CE; Shaw, PJ; Veal, GJ, 2019)		0.51
" This model-based approach validates the use of weight-based dosing as an appropriate alternative for carboplatin in children with either mild renal impairment or normal renal function."( Population pharmacokinetics of carboplatin, etoposide and melphalan in children: a re-evaluation of paediatric dosing formulas for carboplatin in patients with normal or mild impairment of renal function.
Boddy, AV; Duong, JK; Errington, J; Ladenstein, R; Nath, CE; Shaw, PJ; Veal, GJ, 2019)		0.51
" Diagnostic microdosing involves dosing patients or patient samples with subtherapeutic doses of radiolabeled platinum followed by measurement of platinum-DNA adducts in blood or tumor tissue and may be used to predict patient response."( Correlation of Platinum Cytotoxicity to Drug-DNA Adduct Levels in a Breast Cancer Cell Line Panel.
de Vere White, R; Henderson, PT; Malfatti, MA; Pan, CX; Scharadin, TM; Turteltaub, KW; Wang, S; Zimmermann, M, 2018)		0.48
" A dose-response relationship of metformin in combination with standard-of-care paclitaxel (for oestrogen receptor-positive MCF-7 breast tumours) or carboplatin (for triple-negative MDA-MB-468 breast tumours) was investigated in xenograft mice."( Efficacious dose of metformin for breast cancer therapy is determined by cation transporter expression in tumours.
Cai, H; Everett, RS; Thakker, DR, 2019)		0.51
"At the moment there is no evidence from individual studies in children with osteosarcoma or hepatoblastoma treated with different platinum analogues and dosage schedules that underscores the use of amifostine as an otoprotective intervention as compared to no additional treatment."( Medical interventions for the prevention of platinum-induced hearing loss in children with cancer.
van As, JW; van Dalen, EC; van den Berg, H, 2019)		0.51
" PK-guided carboplatin was given after conventionally dosed chemotherapy demonstrated no improvement."( The use of pharmacokinetically guided carboplatin chemotherapy in a pre-term infant with neuroblastoma-associated spinal cord compression.
Errington, J; Hawley, J; McDonald, LG; Tweddle, DA; Veal, GJ, 2019)		0.51
"The exposure-response analysis suggested that intermittent 7-day veliparib 120 mg BID dosing in a 21-day cycle provided additional efficacy without meaningfully impacting the safety and tolerability when co-administered with carboplatin and paclitaxel in patients with BRCA-deficient breast cancer."( Exposure-response analysis to inform the optimal dose of veliparib in combination with carboplatin and paclitaxel in BRCA-mutated advanced breast cancer patients.
Menon, R; Mensing, S; Nuthalapati, S; Ratajczak, CK; Shepherd, SP; Stodtmann, S; Xiong, H, 2019)		0.51
" Conclusions Olaparib in combination with carboplatin and/or paclitaxel resulted in increased hematologic toxicities, making it challenging to establish a dosing regimen that could be tolerated for multiple cycles without dose modifications."( Phase I study of continuous olaparib capsule dosing in combination with carboplatin and/or paclitaxel (Part 1).
Ang, JE; Arkenau, HT; Beijnen, JH; Brunetto, AT; de Bono, JS; de Jonge, MJA; Jager, A; Lolkema, MP; Marchetti, S; Mergui-Roelvink, MWJ; Schellens, JHM; Tchakov, I; van der Biessen, DA; van der Noll, R, 2020)		0.56
" There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed."( A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.
Aghajanian, C; Armstrong, DK; Bell-McGuinn, KM; Chen, A; Duska, LR; Fracasso, PM; Gordon, S; Gray, HJ; Guntupalli, SR; Hagemann, AR; Mathews, CA; Miller, A; Moore, KN; O'Cearbhaill, RE; O'Malley, D; Schilder, RJ; Walker, JL, 2020)		0.56
"Renal function-based carboplatin dosing is a well-accepted practice in pediatric oncology."( Investigating current practices in renal function measurement and carboplatin dosing in children with cancer - a UK perspective.
Barnfield, M; Mogg, JAW; Roberts, E; Veal, GJ, 2020)		0.56
" The study also examined the ability of current and alternate dosing regimens to meet therapeutic targets."( Inability of Current Dosing to Achieve Carboplatin Therapeutic Targets in People with Advanced Non-Small Cell Lung Cancer: Impact of Systemic Inflammation on Carboplatin Exposure and Clinical Outcomes.
Charles, KA; Clarke, SJ; Galettis, P; Harris, BDW; Martin, JH; McLachlan, AJ; Perera, V; Phan, V; Reuter, SE; Szyc, A; Walpole, E, 2020)		0.56
" A Monte Carlo simulation of 100,000 representative NSCLC patients evaluated the ability of the Calvert formula and novel dosing strategies to achieve the targeted therapeutic range."( Inability of Current Dosing to Achieve Carboplatin Therapeutic Targets in People with Advanced Non-Small Cell Lung Cancer: Impact of Systemic Inflammation on Carboplatin Exposure and Clinical Outcomes.
Charles, KA; Clarke, SJ; Galettis, P; Harris, BDW; Martin, JH; McLachlan, AJ; Perera, V; Phan, V; Reuter, SE; Szyc, A; Walpole, E, 2020)		0.56
"An alternate model-based dosing strategy for carboplatin was developed and is predicted to result in consistent drug exposure across the population and improve attainment of therapeutic targets."( Inability of Current Dosing to Achieve Carboplatin Therapeutic Targets in People with Advanced Non-Small Cell Lung Cancer: Impact of Systemic Inflammation on Carboplatin Exposure and Clinical Outcomes.
Charles, KA; Clarke, SJ; Galettis, P; Harris, BDW; Martin, JH; McLachlan, AJ; Perera, V; Phan, V; Reuter, SE; Szyc, A; Walpole, E, 2020)		0.56
"The gemcitabine (GEM)-carboplatin (CBDCA) combination is widely used for non-small cell lung cancer (NSCLC) and has some efficacy in elderly patients; however, a high incidence of thrombocytopenia is observed, and the optimal dosage and administration schedules are unknown."( Phase II Study on Biweekly Combination Therapy of Gemcitabine plus Carboplatin for the Treatment of Elderly Patients with Advanced Non-Small Cell Lung Cancer.
Akamine, S; Ebi, N; Ichiki, M; Matsumoto, T; Nakanishi, Y; Takayama, K; Tokunaga, S; Uchino, J; Yamada, T, 2020)		0.56
" Both weight-based and fixed dosing of Du and Tr were explored."( A phase IB study of durvalumab with or without tremelimumab and platinum-doublet chemotherapy in advanced solid tumours: Canadian Cancer Trials Group Study IND226.
Bebb, G; Bradbury, PA; Brown-Walker, P; Cabanero, M; Dennis, PA; Ellis, PM; Gauthier, I; Goffin, J; Goss, GD; Hao, D; Hilton, J; Hotte, S; Juergens, RA; Kollmannsberger, C; Laskin, J; Laurie, SA; Mates, M; Robinson, A; Seymour, LK; Smoragiewicz, M; Song, X; Sun, X; Tehfe, M; Tomiak, A; Tsao, MS; Tu, D; Wheatley-Price, P, 2020)		0.56
" Furthermore, careful consideration should be given to different methods of storing diluted pharmaceutical drugs and use of DMSO controls due to the potential risk of evaporation and the subsequent effect on dose-response curves."( Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens.
Biermann, J; Engqvist, H; Forssell-Aronsson, E; Helou, K; Karlsson, P; Kovács, A; Larsson, P; Parris, TZ; Werner Rönnerman, E, 2020)		0.56
"Treatment for malignant embryonal brain tumors in young children usually employs cycles of standardly dosed cisplatinum followed by high-dose carboplatinum-containing conditioning with single or tandem autologous stem cell rescue (HDC-ASCR)."( Changes in glomerular filtration rate and clinical course after sequential doses of carboplatin in children with embryonal brain tumors undergoing autologous stem cell transplantation.
Almutereen, M; Elborai, Y; Hafez, H; Lee, MA; Lehmann, L; Maher, OM, 2020)		0.56
" So, larger scale studies are needed to clarify the best approach to carboplatin dosing to insure the optimal balance between efficacy and toxicity."( Changes in glomerular filtration rate and clinical course after sequential doses of carboplatin in children with embryonal brain tumors undergoing autologous stem cell transplantation.
Almutereen, M; Elborai, Y; Hafez, H; Lee, MA; Lehmann, L; Maher, OM, 2020)		0.56
" Given multiple possible dosing schedules and the potential benefit of this regimen for patients with defective DNA repair beyond BRCA, we sought to find the recommended phase II dose (RP2D) and schedule of veliparib in combination with carboplatin in patients with advanced breast cancer, either triple-negative (TNBC) or hormone receptor (HR)-positive, human epidermal growth receptor 2 (HER2) negative with defective Fanconi anemia (FA) DNA-repair pathway based on FA triple staining immunofluorescence assay."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020)		0.56
"The combination of continuous dosing of veliparib and every-3-week carboplatin demonstrated activity and an acceptable toxicity profile."( Phase I Study of Veliparib on an Intermittent and Continuous Schedule in Combination with Carboplatin in Metastatic Breast Cancer: A Safety and [18F]-Fluorothymidine Positron Emission Tomography Biomarker Study.
Amaya, P; Andreopoulou, E; Balasubramanian, P; Berger, M; Carey, A; Chalmers, JJ; Chen, A; Duan, W; Geyer, S; Gillespie, S; Grever, MR; Hall, N; Knopp, MV; Layman, RM; Lustberg, MB; Macrae, E; Miller, BL; Mrozek, E; Ramaswamy, B; Shapiro, CL; Shoben, A; Sparano, J; Stover, DG; Villalona-Calero, MA; Wesolowski, R; Wright, CL; Zhang, J; Zhao, M, 2020)		0.56
" Within the setting of childhood cancer, there are defined groups of patients who present a particular challenge when dosing with carboplatin, including neonates and infants, those who are anephric, and poor prognosis patients receiving high-dose chemotherapy."( Over a decade of experience with carboplatin therapeutic drug monitoring in a childhood cancer setting in the United Kingdom.
Barnett, S; Kong, J; Makin, G; Veal, GJ, 2021)		0.62
" One patient experienced renal dysfunction during the first HDCT, which was alleviated by sufficient hydration and diuretics and resulted in the reduction of melphalan dosage for the second HDCT."( Tandem high-dose chemotherapy with autologous stem cell rescue for stage M high-risk neuroblastoma: Experience using melphalan/etoposide/carboplatin and busulfan/melphalan regimens.
Arakawa, Y; Hiwatari, M; Hogetsu, K; Kato, S; Koh, K; Kubota, Y; Takita, J; Watanabe, K, 2020)		0.56
"Etoposide dosing is based on body surface area."( Pharmacokinetic and Pharmacogenetic Study of Etoposide in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors.
Bay, JO; Chatelut, E; Chevreau, C; Delmas, C; Delva, R; Filleron, T; Fléchon, A; Gravis, G; Gross-Goupil, M; Lafont, T; Lotz, JP; Marsili, S; Massart, C; Moeung, S; Thomas, F, 2020)		0.56
"The present study suggests that neither a priori dose individualization nor dose adaptation using TDM is required validating body surface area dosing of etoposide in the TI-CE protocol."( Pharmacokinetic and Pharmacogenetic Study of Etoposide in High-Dose Protocol (TI-CE) for Advanced Germ Cell Tumors.
Bay, JO; Chatelut, E; Chevreau, C; Delmas, C; Delva, R; Filleron, T; Fléchon, A; Gravis, G; Gross-Goupil, M; Lafont, T; Lotz, JP; Marsili, S; Massart, C; Moeung, S; Thomas, F, 2020)		0.56
"The two dosing schemes (PO and IV) yield similar OS in ES and LS SCLC, however, patients in the PO arm did require more dose modifications."( Comparison of oral versus intravenous etoposide in the management of small-cell lung cancer; A real-world, population-based study.
Abdel-Rahman, O; Karachiwala, H; Morris, D; Tilley, D, 2021)		0.62
" Dosing guidelines for these drugs in children requiring peritoneal dialysis are lacking."( Cisplatin and carboplatin pharmacokinetics in a pediatric patient with hepatoblastoma receiving peritoneal dialysis.
de Kanter, CTMM; Huitema, ADR; Kraal, KCJM; Lilien, MR; Meijs, MJM; Nijstad, AL; van Eijkelenburg, NKA, 2020)		0.56
"Pharmacokinetic data were generated to support clinical dosing decisions, with the aim of adequate exposure and minimal toxicity."( Cisplatin and carboplatin pharmacokinetics in a pediatric patient with hepatoblastoma receiving peritoneal dialysis.
de Kanter, CTMM; Huitema, ADR; Kraal, KCJM; Lilien, MR; Meijs, MJM; Nijstad, AL; van Eijkelenburg, NKA, 2020)		0.56
"Estimated glomerular filtration rate (eGFR) is commonly used to calculate carboplatin doses and capping the eGFR may be used to reduce the risk of excessive dosing and toxicity."( Carboplatin dose capping affects pCR rate in HER2-positive breast cancer patients treated with neoadjuvant Docetaxel, Carboplatin, Trastuzumab, Pertuzumab (TCHP).
Coe, F; Ekholm, M; Horsley, L; Howell, SJ; Wang, X, 2020)		0.56
"To quantify incidence and severity of hypomagnesemia in patients receiving carboplatin-based chemotherapy for OC; to explore a dose-response relationship with carboplatin and assess potential confounding variables."( Carboplatin and hypomagnesemia: Is it really a problem?
Davis, A; Gaughran, G; Qayyum, K; Smyth, L, 2021)		0.62
") are highly effective chemotherapeutic drugs used for the treatment of several types of malignancies, but their application and dosage are limited by their toxic effects on various systems, including neurotoxicity."( Antioxidant Supplementation in the Treatment of Neurotoxicity Induced by Platinum-Based Chemotherapeutics-A Review.
Mihailovic, V; Rosic, G; Selakovic, D; Stankovic, JSK, 2020)		0.56
" Of 159 patients, median age 39 years, 153 received two cycles of carboplatin: 147 dosed at AUC7 and 6 at AUC6."( Two cycles of adjuvant carboplatin for clinical stage 1 testicular seminoma in New Zealand centres: A retrospective analysis of efficacy and long-term events.
Chandran, EA; Chindewere, A; Jameson, MB; North, R, 2021)		0.62
" Despite its common application, there remains a significant controversy and practice variation on its unique method of dosing by area under the curve (AUC)."( Accurate determination of glomerular filtration rate in adults for carboplatin dosing: Moving beyond Cockcroft and Gault.
Akbari, A; Brown, PA; Frechette, D; Tsang, C, 2021)		0.62
"We reviewed all pertinent publications comparing carboplatin AUC-based dosing in adult patients based on the various methods of GFR measurements or estimations in order to provide a comprehensive description of each method's advantages and risks."( Accurate determination of glomerular filtration rate in adults for carboplatin dosing: Moving beyond Cockcroft and Gault.
Akbari, A; Brown, PA; Frechette, D; Tsang, C, 2021)		0.62
" An increased total dosage of paclitaxel and/or cisplatin as part of NAC + CRT and CRT strategies may improve the survival outcome of LACC patients."( Survival outcomes of neoadjuvant chemotherapy-related strategies compared with concurrent chemoradiotherapy for locally advanced cervical cancer: a meta-analysis of randomized controlled trials.
Man, X; Tan, Y; Wang, B; Yang, X, 2021)		0.62
"Chemotherapy requires careful dosing and monitoring and is associated with numerous adverse events."( Impact of Clinical Pharmacy Services on Patient Management in the Chemotherapy Infusion Clinics: A 5-Year Study at a Comprehensive Cancer Center.
Dalbah, MI; Jaddoua, SM; Khalil, HZ; Mashni, OK; Nazer, LH; Rumman, AT; Tuffaha, HW, 2022)		0.72
" A single dosage induced significant improvement of anti-tumour activity (over either the free drugs or the iTSL without FUS-activation) in triple negative breast cancer xenografts tumours in mice."( Image-guided thermosensitive liposomes for focused ultrasound enhanced co-delivery of carboplatin and SN-38 against triple negative breast cancer in mice.
Amrahli, M; Cressey, P; Gedroyc, W; So, PW; Thanou, M; Wright, M, 2021)		0.62
" Binimetinib 30 mg BID (dose level 1 [DL1]) or 45 mg BID (dose level 2 [DL2]) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule."( A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer.
Albaba, H; Arif, S; Bradbury, PA; Chan, M; Chen, EX; Effendi, S; Fung, AS; Gill, S; Graham, DM; Law, JH; Le, LW; Leighl, NB; Pisters, KM; Rothenstein, J; Sawczak, M; Stockley, TL; Trinkaus, M; Zawisza, D; Zhang, T; Zurawska, U, 2021)		0.62
"A total of 26 patients were dosed (cohort 3: 14; cohorts 1, 2, and 4 combined: 12)."( A Phase 1 Study Evaluating Rovalpituzumab Tesirine in Frontline Treatment of Patients With Extensive-Stage SCLC.
Burns, TF; Camidge, DR; Chen, C; Dowlati, A; Hann, CL; Koch, MM; Komarnitsky, P; Ludwig, C; Morgensztern, D; Nimeiri, H; Patel, M; Ward, PJ, 2021)		0.62
" This study aims to improve the determination of carboplatin dosage to know the real impact of carboplatin capping and to find the optimum balance between excessive toxicity and substandard therapeutics outcomes."( Safety and Survival Outcomes in Lung Cancer Patients Receiving Carboplatin: Impact of Uncapped Dosage.
Boulanger, C; Dewolf, M; Le Bozec, A; Maréchal, A; Mongaret, C; Slimano, F, 2021)		0.62
" Sequential and concurrent combination dosing schedules were assessed."( Ceralasertib (AZD6738), an Oral ATR Kinase Inhibitor, in Combination with Carboplatin in Patients with Advanced Solid Tumors: A Phase I Study.
Berges, A; Cheung, SYA; Clack, G; Dean, E; El-Khouiery, A; Felicetti, B; Frewer, P; Goldwin, A; Hollingsworth, SJ; Irurzun-Arana, I; Jones, GN; Krebs, MG; Lau, A; Lopez, J; Pierce, AJ; Postel-Vinay, S; Smith, SA; Soria, JC; Stephens, C; Yap, TA, 2021)		0.62
"Adequate coordination with Paediatric Oncology is essential to carry out active surveillance for ototoxicity and to modify, if possible, the dosage or type of chemotherapy in case hearing is affected."( Ototoxicity in cancer survivors: Experience and proposal of a surveillance protocol.
Antonio Villegas-Rubio, J; de Lucio-Delgado, A; Gómez-Martínez, JR; Luis Llorente-Pendás, J; Martínez-González, P; Núñez-Batalla, F; Sánchez-Canteli, M, 2021)		0.62
" Body size-based dosing is used for most anticancer drugs used in infants."( Clinical pharmacology of cytotoxic drugs in neonates and infants: Providing evidence-based dosing guidance.
Barnett, S; Bérénos, IM; Carruthers, V; Huitema, ADR; Kong, J; Lalmohamed, A; Nijstad, AL; Parke, E; Tweddle, DA; Veal, GJ; Zwaan, CM, 2022)		0.72
" Here we present exploratory analyses by paclitaxel dosing schedule and germline BRCA (gBRCA) status."( Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.
Aghajanian, C; Bookman, MA; Chan, JK; Coleman, RL; Dinh, MH; Fleming, GF; Friedlander, M; Hashiba, H; Moore, KN; O'Malley, DM; Okamoto, A; Ratajczak, C; Steffensen, KD; Swisher, EM; Tewari, KS; Wu, M, 2022)		0.72
" PFS was assessed by paclitaxel dosing schedule using a Cox proportional hazard model adjusted by treatment arm and stratification factors; safety was analyzed based on paclitaxel dosing schedule and gBRCA status."( Impact of veliparib, paclitaxel dosing regimen, and germline BRCA status on the primary treatment of serous ovarian cancer - an ancillary data analysis of the VELIA trial.
Aghajanian, C; Bookman, MA; Chan, JK; Coleman, RL; Dinh, MH; Fleming, GF; Friedlander, M; Hashiba, H; Moore, KN; O'Malley, DM; Okamoto, A; Ratajczak, C; Steffensen, KD; Swisher, EM; Tewari, KS; Wu, M, 2022)		0.72
" This translated to in vivo antitumor activity, with tumor control requiring continuous dosing and free plasma exposures, which correlated with induction of pCHK1, pRAD50, and γH2AX."( ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib.
Bargh-Dawson, H; Brown, E; Gerrard, J; Hughes, AM; Jones, GN; Lau, A; O'Connor, MJ; Odedra, R; Wallez, Y; Wijnhoven, PWG; Wilson, Z; Young, LA, 2022)		0.72
" However, there is conflicting evidence regarding the optimal dosing schedule of paclitaxel when combined with carboplatin in this setting."( Weekly versus tri-weekly paclitaxel with carboplatin for first-line treatment in women with epithelial ovarian cancer.
Clamp, A; Cook, A; Goh, BC; Goh, RM; Huang, RY; James, E; Ngoi, NY; Soon, YY; Syn, NL; Tan, DS, 2022)		0.72
"Carboplatin remains integral for treatment of gynaecological malignancies and dosing is based on glomerular filtration rate (GFR)."( Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers.
Bennett, R; Eremeishvili, K; Ghosh, S; Kalofonou, F; Krell, J; Kristeleit, R; McNeish, I; Montes, A; Samani, A; Tookman, L; Whear, S, 2022)		0.72
"We surveyed several UK National Health Service Trusts to assess carboplatin dosing practise."( Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers.
Bennett, R; Eremeishvili, K; Ghosh, S; Kalofonou, F; Krell, J; Kristeleit, R; McNeish, I; Montes, A; Samani, A; Tookman, L; Whear, S, 2022)		0.72
" In the absence of validation, CG-AdBW or CamGFR v2 is likely to perform well while unadjusted CG/Wright formulae or AUC6 dosing should be avoided."( Glomerular filtration rate estimation for carboplatin dosing in patients with gynaecological cancers.
Bennett, R; Eremeishvili, K; Ghosh, S; Kalofonou, F; Krell, J; Kristeleit, R; McNeish, I; Montes, A; Samani, A; Tookman, L; Whear, S, 2022)		0.72
" In multiple LUSC patient-derived xenograft and cell line tumor models, CC-115 plus platinum-based doublet chemotherapy significantly inhibited tumor growth and increased overall survival as compared with either treatment alone at clinically relevant dosing schedules."( Inhibition of Mtorc1/2 and DNA-PK via CC-115 Synergizes with Carboplatin and Paclitaxel in Lung Squamous Cell Carcinoma.
Castellano, GM; Garbuzenko, OB; Malhotra, J; Minko, T; Pine, SR; Sabaawy, HE; Zeeshan, S, 2022)		0.72
" Dosing of carboplatin is complicated due to its relationship to renal function and narrow therapeutic index."( Carboplatin dose calculations for patients with lung cancer: significant dose differences found depending on dosing equation choice.
Akgül, S; Chan, BA; Manders, PM, 2022)		0.72
"We compared these formulae to identify patient profiles that were associated with significant carboplatin dose variation by retrospectively analysing the carboplatin dosing of 96 patients with lung cancer."( Carboplatin dose calculations for patients with lung cancer: significant dose differences found depending on dosing equation choice.
Akgül, S; Chan, BA; Manders, PM, 2022)		0.72
"We have therefore confirmed significant differences in carboplatin dosing depending on the equation used in our modern patient population and suggest that use of CKD-EPI provides the most clinically appropriate carboplatin dosing and should be implemented as the new standard of care internationally."( Carboplatin dose calculations for patients with lung cancer: significant dose differences found depending on dosing equation choice.
Akgül, S; Chan, BA; Manders, PM, 2022)		0.72
"Continuous dosing of ipatasertib with chemotherapy was safe and well-tolerated."( Phase I Trial of Ipatasertib Plus Carboplatin, Carboplatin/Paclitaxel, or Capecitabine and Atezolizumab in Metastatic Triple-Negative Breast Cancer.
Bozoghlanian, M; Cui, Y; Frankel, PH; Martinez, N; Murga, M; Patel, N; Ruel, C; Schmolze, D; Stewart, D; Tang, A; Tumyan, L; Vora, L; Waisman, J; Yost, SE; Yuan, Y, 2023)		0.91
"Carboplatin is generally dosed based on a modified Calvert formula, in which the Cockcroft-Gault-based creatinine clearance (CRCL) is used as proxy for the glomerular filtration rate (GFR)."( Optimizing carboplatin dosing by an improved prediction of carboplatin clearance using a CT-enhanced estimate of renal function.
Beijnen, JH; Dorlo, TPC; Huitema, ADR; Moeskops, P; Molenaar-Kuijsten, L; Pieters, TT; Rijkhorst, EJ; Rookmaaker, MB; Steeghs, N; Veldhuis, WB, 2023)		0.91
" Therefore, the CRAFT might be an alternative for dose capping while still dosing accurately."( Optimizing carboplatin dosing by an improved prediction of carboplatin clearance using a CT-enhanced estimate of renal function.
Beijnen, JH; Dorlo, TPC; Huitema, ADR; Moeskops, P; Molenaar-Kuijsten, L; Pieters, TT; Rijkhorst, EJ; Rookmaaker, MB; Steeghs, N; Veldhuis, WB, 2023)		0.91
" Concerns about excessive toxicity-as many are infants and/or undergo nephrectomy-have resulted in decreased chemotherapy dosing and omission of the nephrotoxic drug ifosfamide in collaborative group studies."( Tolerability of ifosfamide-containing regimen in patients with high-risk renal and INI-1-deficient tumors.
Benedetti, DJ; Kao, PC; Ma, C; Marcus, KJ; Mullen, EA; Wong, CI, 2023)		0.91
"To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl)."( Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.
Aghajanian, C; Argenta, P; Backes, F; Bookman, M; Cohn, DE; Friedlander, M; Gershenson, DM; Goodheart, MJ; Gray, H; Lee, RB; Lichtman, SM; Miller, A; Mutch, DG; O'Cearbhaill, RE; Praiss, AM; Sabbatini, P; Secord, AA; Smith, J; Tewari, KS; Van Le, L; Wahner Hendrickson, AE; Wenham, RM, 2023)		0.91
" We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas."( Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study.
Aghajanian, C; Argenta, P; Backes, F; Bookman, M; Cohn, DE; Friedlander, M; Gershenson, DM; Goodheart, MJ; Gray, H; Lee, RB; Lichtman, SM; Miller, A; Mutch, DG; O'Cearbhaill, RE; Praiss, AM; Sabbatini, P; Secord, AA; Smith, J; Tewari, KS; Van Le, L; Wahner Hendrickson, AE; Wenham, RM, 2023)		0.91
"To optimally dose childhood cancer patients it is essential that we apply evidence-based dosing approaches."( Generation of evidence-based carboplatin dosing guidelines for neonates and infants.
Barnett, S; Makin, G; Osborne, C; Tweddle, DA; Veal, GJ, 2023)		0.91
" These parameters were utilised to assess current dosing variability, determine doses required to achieve target AUC values and predict change in AUC using the modified dose."( Generation of evidence-based carboplatin dosing guidelines for neonates and infants.
Barnett, S; Makin, G; Osborne, C; Tweddle, DA; Veal, GJ, 2023)		0.91
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (20)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, MAJOR APURINIC/APYRIMIDINIC ENDONUCLEASEHomo sapiens (human)Potency11.22020.003245.467312,589.2998AID2517
Chain A, TYROSYL-DNA PHOSPHODIESTERASEHomo sapiens (human)Potency63.09570.004023.8416100.0000AID485290
Chain A, Putative fructose-1,6-bisphosphate aldolaseGiardia intestinalisPotency14.09190.140911.194039.8107AID2451
acetylcholinesteraseHomo sapiens (human)Potency21.87610.002541.796015,848.9004AID1347397
phosphopantetheinyl transferaseBacillus subtilisPotency6.30960.141337.9142100.0000AID1490
RAR-related orphan receptor gammaMus musculus (house mouse)Potency11.20850.006038.004119,952.5996AID1159521; AID1159523
estrogen receptor 2 (ER beta)Homo sapiens (human)Potency33.49150.000657.913322,387.1992AID1259377
GVesicular stomatitis virusPotency38.90180.01238.964839.8107AID1645842
cytochrome P450 2D6Homo sapiens (human)Potency19.49710.00108.379861.1304AID1645840
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency0.79430.035520.977089.1251AID504332
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency39.81070.354828.065989.1251AID504847
histone-lysine N-methyltransferase 2A isoform 2 precursorHomo sapiens (human)Potency63.09570.010323.856763.0957AID2662
nuclear factor erythroid 2-related factor 2 isoform 1Homo sapiens (human)Potency23.46780.000627.21521,122.0200AID743202; AID743219
DNA polymerase kappa isoform 1Homo sapiens (human)Potency8.91250.031622.3146100.0000AID588579
histone acetyltransferase KAT2A isoform 1Homo sapiens (human)Potency19.95260.251215.843239.8107AID504327
Interferon betaHomo sapiens (human)Potency38.90180.00339.158239.8107AID1645842
HLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)Potency38.90180.01238.964839.8107AID1645842
Inositol hexakisphosphate kinase 1Homo sapiens (human)Potency38.90180.01238.964839.8107AID1645842
cytochrome P450 2C9, partialHomo sapiens (human)Potency38.90180.01238.964839.8107AID1645842
ATP-dependent phosphofructokinaseTrypanosoma brucei brucei TREU927Potency3.16230.060110.745337.9330AID492961
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (45)

Processvia Protein(s)Taxonomy
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell activation involved in immune responseInterferon betaHomo sapiens (human)
cell surface receptor signaling pathwayInterferon betaHomo sapiens (human)
cell surface receptor signaling pathway via JAK-STATInterferon betaHomo sapiens (human)
response to virusInterferon betaHomo sapiens (human)
positive regulation of autophagyInterferon betaHomo sapiens (human)
cytokine-mediated signaling pathwayInterferon betaHomo sapiens (human)
natural killer cell activationInterferon betaHomo sapiens (human)
positive regulation of peptidyl-serine phosphorylation of STAT proteinInterferon betaHomo sapiens (human)
cellular response to interferon-betaInterferon betaHomo sapiens (human)
B cell proliferationInterferon betaHomo sapiens (human)
negative regulation of viral genome replicationInterferon betaHomo sapiens (human)
innate immune responseInterferon betaHomo sapiens (human)
positive regulation of innate immune responseInterferon betaHomo sapiens (human)
regulation of MHC class I biosynthetic processInterferon betaHomo sapiens (human)
negative regulation of T cell differentiationInterferon betaHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIInterferon betaHomo sapiens (human)
defense response to virusInterferon betaHomo sapiens (human)
type I interferon-mediated signaling pathwayInterferon betaHomo sapiens (human)
neuron cellular homeostasisInterferon betaHomo sapiens (human)
cellular response to exogenous dsRNAInterferon betaHomo sapiens (human)
cellular response to virusInterferon betaHomo sapiens (human)
negative regulation of Lewy body formationInterferon betaHomo sapiens (human)
negative regulation of T-helper 2 cell cytokine productionInterferon betaHomo sapiens (human)
positive regulation of apoptotic signaling pathwayInterferon betaHomo sapiens (human)
response to exogenous dsRNAInterferon betaHomo sapiens (human)
B cell differentiationInterferon betaHomo sapiens (human)
natural killer cell activation involved in immune responseInterferon betaHomo sapiens (human)
adaptive immune responseInterferon betaHomo sapiens (human)
T cell activation involved in immune responseInterferon betaHomo sapiens (human)
humoral immune responseInterferon betaHomo sapiens (human)
positive regulation of T cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
adaptive immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class I via ER pathway, TAP-independentHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of T cell anergyHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
defense responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
detection of bacteriumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-12 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of interleukin-6 productionHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protection from natural killer cell mediated cytotoxicityHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
innate immune responseHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
regulation of dendritic cell differentiationHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
antigen processing and presentation of endogenous peptide antigen via MHC class IbHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
inositol phosphate metabolic processInositol hexakisphosphate kinase 1Homo sapiens (human)
phosphatidylinositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
negative regulation of cold-induced thermogenesisInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol phosphate biosynthetic processInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (18)

Processvia Protein(s)Taxonomy
cytokine activityInterferon betaHomo sapiens (human)
cytokine receptor bindingInterferon betaHomo sapiens (human)
type I interferon receptor bindingInterferon betaHomo sapiens (human)
protein bindingInterferon betaHomo sapiens (human)
chloramphenicol O-acetyltransferase activityInterferon betaHomo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
signaling receptor bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
peptide antigen bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
TAP bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
protein-folding chaperone bindingHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
inositol-1,3,4,5,6-pentakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol heptakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
protein bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
ATP bindingInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 1-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol hexakisphosphate 3-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol 5-diphosphate pentakisphosphate 5-kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
inositol diphosphate tetrakisphosphate kinase activityInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (22)

Processvia Protein(s)Taxonomy
extracellular spaceInterferon betaHomo sapiens (human)
extracellular regionInterferon betaHomo sapiens (human)
Golgi membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
endoplasmic reticulumHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
Golgi apparatusHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
cell surfaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
ER to Golgi transport vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
secretory granule membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
phagocytic vesicle membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
early endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
recycling endosome membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular exosomeHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
lumenal side of endoplasmic reticulum membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
MHC class I protein complexHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
extracellular spaceHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
external side of plasma membraneHLA class I histocompatibility antigen, B alpha chain Homo sapiens (human)
fibrillar centerInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
cytosolInositol hexakisphosphate kinase 1Homo sapiens (human)
nucleusInositol hexakisphosphate kinase 1Homo sapiens (human)
cytoplasmInositol hexakisphosphate kinase 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (35)

Assay IDTitleYearJournalArticle
AID504749qHTS profiling for inhibitors of Plasmodium falciparum proliferation2011Science (New York, N.Y.), Aug-05, Volume: 333, Issue:6043
Chemical genomic profiling for antimalarial therapies, response signatures, and molecular targets.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1347106qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for control Hh wild type fibroblast cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347093qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347091qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347105qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347096qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347094qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347092qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347104qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347102qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347407qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS Pharmaceutical Collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID1347425Rhodamine-PBP qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347108qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347098qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347097qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347100qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347099qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347107qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347090qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347089qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347103qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347424RapidFire Mass Spectrometry qHTS Assay for Modulators of WT P53-Induced Phosphatase 1 (WIP1)2019The Journal of biological chemistry, 11-15, Volume: 294, Issue:46
Physiologically relevant orthogonal assays for the discovery of small-molecule modulators of WIP1 phosphatase in high-throughput screens.
AID1347095qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347101qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells2018Oncotarget, Jan-12, Volume: 9, Issue:4
Quantitative high-throughput phenotypic screening of pediatric cancer cell lines identifies multiple opportunities for drug repurposing.
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (12,100)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990367 (3.03)18.7374
1990's2459 (20.32)18.2507
2000's3582 (29.60)29.6817
2010's4339 (35.86)24.3611
2020's1353 (11.18)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials4,001 (31.03%)5.53%
Reviews1,163 (9.02%)6.00%
Case Studies1,591 (12.34%)4.05%
Observational82 (0.64%)0.25%
Other6,058 (46.98%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (2781)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
A Randomized Phase II Trial of Carboplatin and Gemcitabine +/- Vandetanib in First Line Treatment of Advanced Urothelial Cell Cancer in Patients Who Are Not Suitable to Receive Cisplatin [NCT01191892]Phase 282 participants (Actual)Interventional2010-06-30Completed
A Phase II Trial of Trastuzumab Plus Weekly Ixabepilone(BMS-247550) and Carboplatin in Patients With HER2/Neu-Positive Metastatic Breast Cancer [NCT00077376]Phase 261 participants (Actual)Interventional2005-03-31Completed
A Phase IB and Randomized Open-Label Phase II Study of Berzosertib (M6620, VX-970) in Combination With Carboplatin/Gemcitabine/Pembrolizumab in Patients With Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer of Squamous Cell Histology [NCT04216316]Phase 1/Phase 2106 participants (Anticipated)Interventional2021-04-14Active, not recruiting
A Phase 1 Study of BAL0891 as Monotherapy and in Combination With Chemotherapy in Patients With Advanced Solid Tumors [NCT05768932]Phase 1120 participants (Anticipated)Interventional2022-12-14Recruiting
A Randomized Phase II Trial of Carboplatin-Paclitaxel With or Without Ramucirumab in Patients With Unresectable Locally Advanced, Recurrent, or Metastatic Thymic Carcinoma [NCT03694002]Phase 266 participants (Anticipated)Interventional2019-03-20Active, not recruiting
NCI 10147: A Phase II Randomized Study of Topotecan/Carboplatin With or Without Veliparib in Advanced Myeloproliferative Disorders and Chronic Myelomonocytic Leukemia (CMML) [NCT03289910]Phase 260 participants (Anticipated)Interventional2018-06-08Active, not recruiting
A Phase 3, Randomized, Global Trial of Nivolumab and Epacadostat With Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in First-line Treatment of Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) [NCT03348904]Phase 32 participants (Actual)Interventional2017-12-27Terminated(stopped due to Study halted prematurely and will not resume; participants are no longer being examined or receiving intervention.)
Phase II Randomized Open-Label Trial of the EGFR Tyrosine Kinase Inhibitor OSI-774 (Tarceva™) in Combination With Paclitaxel and Carboplatin Prior to Surgery in Resectable Stage IIIA (N2) and IIIB (T4 N2) NSCLC: A Clinical Outcome and Biological Endpoint [NCT00063258]Phase 25 participants (Actual)Interventional2003-06-30Terminated(stopped due to Low accrual rate)
PHASE I/II TRIAL OF SEQUENTIAL TAXOL/IFOSFAMIDE AND DOSEINTENSIVE CARBOPLATIN/ETOPOSIDE WITH STEM CELL SUPPORT IN CISPLATIN-RESISTANT GERM CELL TUMOR PATIENTS WITH UNFAVORABLE PROGNOSTIC FEATURES [NCT00002558]Phase 1/Phase 2108 participants (Actual)Interventional1994-01-31Completed
Phase II, Randomized, Open-Label Trial of Biweekly Pemetrexed Plus Gemcitabine vs. Pemetrexed or Pemetrexed Plus Carboplatin in Relapsed Non Small Cell Lung Cancer After Neoadjuvant or Adjuvant Chemotherapy [NCT00356525]Phase 241 participants (Actual)Interventional2006-09-30Terminated(stopped due to Stopped early due to low enrollment)
A Phase I/II Pilot Study of Ifosfamide, Carboplatin and Etoposide Therapy (ICE) and SGN-30 (NSC# 731636, IND#) in Children With CD30+ Recurrent Anaplastic Large Cell Lymphoma [NCT00354107]Phase 1/Phase 25 participants (Actual)Interventional2007-01-31Terminated
A Phase II Trial of Neoadjuvant Bevacizumab, Docetaxel and Carboplatin for Triple Negative Breast Cancer (Neat Trial) [NCT01208480]Phase 245 participants (Actual)Interventional2010-09-30Completed
CIRCCa - A Randomized Double Blind Phase II Trial of Carboplatin-Paclitaxel Plus Cediranib Versus Carboplatin-Paclitaxel Plus Placebo in Metastatic/Recurrent Cervical Cancer [NCT01229930]Phase 2130 participants (Anticipated)Interventional2010-06-30Completed
A Randomized Phase II Clinical Trial of Nab-Paclitaxel and Carboplatin Compared With Gemcitabine and Carboplatin as First-line Therapy in Advanced Squamous Cell Carcinoma of Lung [NCT01236716]Phase 2126 participants (Actual)Interventional2010-11-30Completed
IMRT Combined With Carboplatin Versus IMRT Combined With Carboplatin and Fluorouracil in the Treatment of Locally Advanced Esophageal Cancer in Elderly Patients With High Risk of Chemotherapy: a Randomized Controlled Clinical Study [NCT03910634]Phase 2264 participants (Anticipated)Interventional2019-04-09Enrolling by invitation
A Phase IB Study of the Histone Deacetylase Inhibitor Panobinostat (LBH589) Given Orally in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumors [NCT01159418]Phase 136 participants (Anticipated)Interventional2008-06-30Active, not recruiting
Tandem High-Dose Chemotherapy (HDCT) With Peripheral-Blood Stem-Cell Rescue for Patients With Metastatic Germ-Cell Tumors Failing First-Line Treatment [NCT01172912]Phase 247 participants (Anticipated)Interventional2010-10-31Recruiting
A Phase I/II Open Label Multi Center Study of Immune Checkpoint Therapy With Nivolumab for Patients With Locally Advanced Esophageal Squamous Cell Carcinoma [NCT03278626]Phase 1/Phase 212 participants (Actual)Interventional2017-06-27Terminated(stopped due to The study was stopped earlier than anticipated due to slow accrual)
A Single Arm Trial of Systemic And Subtenon Chemotherapy For Groups C And D Intraocular Retinoblastoma [NCT00072384]Phase 330 participants (Actual)Interventional2007-04-16Completed
Paclitaxel/Carboplatin (PC) Followed by Gefitinib or Paclitaxel/Carboplatin (PC) in Advanced Non-small Cell Lung Cancer (NSCLC): Randomized Phase II Study [NCT01196234]Phase 284 participants (Actual)Interventional2009-12-31Completed
A Phase II Randomized Trial Evaluating the Effect of Trastuzumab on Disease Free Survival in Early Stage HER2-Negative Breast Cancer Patients With ERBB2 Expressing Bone Marrow Disseminated Tumor Cells [NCT01779050]Phase 27 participants (Actual)Interventional2013-12-19Terminated(stopped due to Loss of study funding)
A Prospective, Randomized Controlled Study to Evaluate the Efficacy and Safety of Durvalumab Combined With Neoadjuvant Therapy in Patients With Local Advanced Esophageal Squamous Cell Carcinoma [NCT04568200]Phase 260 participants (Anticipated)Interventional2020-06-19Recruiting
A Phase II Evaluation of Avastin in Combination With Docetaxel and Carboplatin as Chemotherapy in Patients With Metastatic Non-Small Cell Lung Cancer [NCT00271505]Phase 243 participants (Actual)Interventional2005-12-05Completed
A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus Carboplatin and Paclitaxel Plus Concurrent Bevacizumab (NSC # 704865) Followed by Placebo, Versus Carboplatin and Paclitaxel Plus Concurrent and Extended Bevacizumab, in Women With Newly [NCT00262847]Phase 31,873 participants (Actual)Interventional2005-09-30Completed
to Evaluate SCT510 Compared to Avasitin Respectively Combined Paclitaxel and Carboplatin First-line Treatment of Locally Advanced and Metastatic or Recurrent Squamous Cell Non-small Cell Lung Cancer Efficacy and Safety [NCT03792074]Phase 3560 participants (Anticipated)Interventional2019-02-28Not yet recruiting
[NCT01347424]Phase 240 participants (Anticipated)Interventional2011-01-31Active, not recruiting
A Sequential Approach to the Treatment of Muscle Invasive, Non-Metastatic Urothelial Carcinoma of the Bladder: A Phase II Trial of Neoadjuvant Gemcitabine, Paclitaxel and Carboplatin With Molecular Correlates [NCT00045630]Phase 277 participants (Actual)Interventional2003-01-31Completed
Feasibility of Using Concurrent Carboplatin and Reduced Dose Craniospinal Radiation (24Gy) for Metastatic Medulloblastoma, High-Risk Supratentorial PNET and Metastatic PNET [NCT01542736]Phase 28 participants (Actual)Interventional2007-05-31Completed
A Phase II Trial of Conformal Radiation Therapy for Pediatric Patients With Localized Ependymoma, Chemotherapy Prior to Second Surgery for Incompletely Resected Ependymoma and Observation for Completely Resected, Differentiated, Supratentorial Ependymoma [NCT00027846]Phase 2378 participants (Actual)Interventional2003-08-31Completed
An Open-label, Multicenter Phase Ib/II Clinical Study to Evaluate the Safety and Efficacy of LBL-024 Combined With Etoposide and Platinum in the First-line Treatment of Patients With Advanced Neuroendocrine Carcinoma (NEC) [NCT06157827]Phase 1/Phase 268 participants (Anticipated)Interventional2023-12-05Not yet recruiting
A Randomized Phase III Trial of Chemo-Immunotherapy vs Immunotherapy Alone for the Vulnerable Older Adult With Advanced Non-Small Cell Lung Cancer: The ACHIEVE Study [NCT06096844]Phase 3304 participants (Anticipated)Interventional2024-02-16Not yet recruiting
A Randomized, Open-Label, Multicenter, Phase 2, Umbrella Study to Evaluate the Preliminary Efficacy, Safety, and Pharmacodynamics of Tislelizumab Monotherapy and Multiple Tislelizumab-based Immunotherapy Combinations With and Without Chemotherapy as Neoad [NCT05577702]Phase 2120 participants (Anticipated)Interventional2023-02-15Recruiting
LuCa-MERIT-1: First-in-human, Open Label, Phase I Dose Confirmation Trial Evaluating the Safety, Tolerability and Preliminary Efficacy of BNT116 Alone and in Combinations in Patients With Advanced Non-small Cell Lung Cancer [NCT05142189]Phase 1130 participants (Anticipated)Interventional2022-06-17Recruiting
A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After O [NCT04988295]Phase 3776 participants (Actual)Interventional2021-11-17Active, not recruiting
A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT04538664]Phase 3308 participants (Actual)Interventional2020-10-13Active, not recruiting
An Open-label, Randomized, Controlled Phase 3 Study of Enfortumab Vedotin in Combination With Pembrolizumab Versus Chemotherapy Alone in Previously Untreated Locally Advanced or Metastatic Urothelial Cancer [NCT04223856]Phase 3990 participants (Anticipated)Interventional2020-03-30Recruiting
Randomized Phase III Trial of MEDI4736 (Durvalumab) as Concurrent and Consolidative Therapy or Consolidative Therapy Alone for Unresectable Stage 3 NSCLC [NCT04092283]Phase 3660 participants (Anticipated)Interventional2020-04-29Active, not recruiting
An Open-label Phase 1/1b Study to Evaluate the Safety and Pharmacokinetics of JNJ-73841937 (Lazertinib), a Third Generation EGFR-TKI, as Monotherapy or in Combinations With JNJ-61186372, a Human Bispecific EGFR and cMet Antibody in Participants With Advan [NCT04077463]Phase 1460 participants (Anticipated)Interventional2019-09-04Recruiting
Phase I Study of Radiation Dose Intensification With Accelerated Hypofractionated Intensity Modulated Radiation Therapy and Concurrent Carboplatin and Paclitaxel for Inoperable Esophageal Cancer [NCT04046575]Phase 120 participants (Anticipated)Interventional2019-11-07Recruiting
Randomized Phase II Clinical Trial of Cisplatin/Carboplatin and Etoposide (CE) Alone or in Combination With Nivolumab as Frontline Therapy for Extensive Stage Small Cell Lung Cancer (ED-SCLC) [NCT03382561]Phase 2160 participants (Actual)Interventional2018-05-02Active, not recruiting
A Phase 1, First-in-Human, Open-Label, Dose Escalation Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer [NCT02609776]Phase 1751 participants (Actual)Interventional2016-05-24Active, not recruiting
A Randomized Phase III Trial Evaluating Pathologic Complete Response Rates in Patients With Hormone Receptor-Positive, HER2-Positive, Large Operable and Locally Advanced Breast Cancer Treated With Neoadjuvant Therapy of Docetaxel, Carboplatin, Trastuzumab [NCT02003209]Phase 3315 participants (Actual)Interventional2014-01-15Active, not recruiting
A Dose Finding Study Followed by Phase II Randomized, Placebo-Controlled Study of Veliparib (ABT-888) Added to Chemoradiotherapy With Carboplatin and Paclitaxel for Unresectable Stage III Non-small Cell Lung Cancer (NSCLC), (NCI Study Number 8811) [NCT01386385]Phase 1/Phase 253 participants (Actual)Interventional2011-06-20Active, not recruiting
A Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer [NCT00588770]Phase 3403 participants (Actual)Interventional2008-08-08Active, not recruiting
A Feasibility Study of Vorinostat (SAHA) Combined With Isotretinoin and Chemotherapy in Infants With Embryonal Tumors of the Central Nervous System [NCT00867178]Phase 133 participants (Actual)Interventional2009-02-25Completed
A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-348 as Monotherapy, in Combination With Carboplatin or in Combination With Docetaxel in Subjects With Advanced Solid Tumors [NCT01110486]Phase 1102 participants (Actual)Interventional2010-03-31Completed
Phase I Study of Intraperitoneal Carboplatin With Intravenous Paclitaxel and Bevacizumab in Patients With Previously Untreated Epithelial Ovarian Carcinoma or Primary Peritoneal Carcinoma [NCT01220154]Phase 19 participants (Actual)Interventional2010-10-31Active, not recruiting
A Phase 1 Study of Linifanib (ABT-869) in Combination With Carboplatin/Paclitaxel in Japanese Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) as First-Line Treatment [NCT01225302]Phase 112 participants (Actual)Interventional2010-09-30Completed
Standard Chemotherapy Plus Moxifloxacin as First-line Treatment for Metastatic Triple-negative Breast Cancer : a Multicenter, Double-blind, Placebo-controlled, Phase 3 Trial [NCT04722978]Phase 3228 participants (Anticipated)Interventional2021-04-20Recruiting
Open-label, Phase 2 Study of Tusamitamab Ravtansine (IBI126) Combined With Sintilimab and Tusamitamab Ravtansine (IBI126) Combined With Sintilimab Plus Platinum-based Chemotherapy and Pemetrexed in Subjects With CEACAM5 Positive Expression Advanced/Metast [NCT05849246]Phase 2130 participants (Anticipated)Interventional2023-05-30Not yet recruiting
Disitamab Vedotin Combined Therapy for Locally Advanced or Metastatic NSCLC With HER2 Alterations, a Phase II Study [NCT05847764]Phase 295 participants (Anticipated)Interventional2023-05-31Not yet recruiting
Short-term Sintilimab in Combination With Taxane and Carboplatin for Neoadjuvant Therapy in Triple-negative Breast Cancer, an Open-labeled, Single Arm Trial [NCT05843292]Phase 448 participants (Anticipated)Interventional2023-07-01Not yet recruiting
Phase II Trial of Transoral Surgical Resection Followed by De-escalated Adjuvant IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer [NCT05388773]Phase 2150 participants (Anticipated)Interventional2022-06-27Recruiting
"The Upproach Approach: A Phase 2 Study Of Upfront Intensity Modulated Proton Beam Therapy (Impt) And Concurrent Chemotherapy For Post-Operative Treatment In Loco-Regionally Advanced Endometrial Cancer" [NCT04527900]Phase 221 participants (Anticipated)Interventional2021-02-23Recruiting
A Phase 1 Study of Trametinib in Combination With Chemoradiation for KRAS Mutant Non-small Cell Lung Cancer [NCT01912625]Phase 116 participants (Actual)Interventional2013-10-28Terminated(stopped due to Inadequate accrual rate)
A Randomized, Open Label, Multi-center Phase II-III Neoadjuvant Study Comparing the Efficacy and Safety of ARX788 Combined With Pyrotinib Maleate Versus TCBHP (Trastuzumab Plus Pertuzumab With Docetaxel and Carboplatin) in Patients With HER2-positive Brea [NCT05426486]Phase 2/Phase 3150 participants (Anticipated)Interventional2022-05-23Recruiting
Study of Atezolizumab in Combination With Carboplatin + Paclitaxel +Bevacizumab vs With Pemetrexed + Cisplatin or Carboplatin With Stage IV NON-SQUAMOUS NON-SMALL CELL LUNG CANCER With EGFR(+) or ALK(+) [NCT03991403]Phase 3228 participants (Actual)Interventional2019-08-27Active, not recruiting
A Phase I Study of NK012 in Combination With Carboplatin in Patients With Advanced Solid Tumors Followed by a Dose Expansion Phase in Patients With Triple Negative Metastatic Breast Cancer [NCT01238952]Phase 14 participants (Actual)Interventional2010-07-31Completed
A Phase I/II Study of Ruxolitinib With Front-Line Neoadjuvant and Post-Surgical Therapy in Patients With Advanced Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer [NCT02713386]Phase 1/Phase 2147 participants (Anticipated)Interventional2016-11-14Active, not recruiting
Multicenter Open-Label Single-Arm Trial of the Efficacy and Safety of BCD-100 in Combination With Platinum-Based Chemotherapy and Bevacizumab as First Line Treatment in Patients With Recurrent, Persistent or Metastatic Cervical Cancer [NCT03912402]Phase 249 participants (Anticipated)Interventional2018-12-25Recruiting
Phase 1A/B Study of Combination Carboplatin, Paclitaxel and Ridaforolimus in Patients With Solid, Endometrial, and Ovarian Cancers [NCT01256268]Phase 124 participants (Actual)Interventional2011-06-13Completed
Phase I Trial of CPI-0209 in Combination With Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer [NCT05942300]Phase 130 participants (Anticipated)Interventional2023-12-31Not yet recruiting
Prospective, One-arm, Phase II Clinical Study of Tirelizumab in Combination With Carboplatin and Albumin-binding Paclitaxel for Neoadjuvant Therapy in Patients With Resectable Squamous Cell Carcinoma of the Head and Neck [NCT05941338]Phase 2100 participants (Anticipated)Interventional2023-03-01Recruiting
Pembrolizumab Plus Bevacizumab and Chemotherapy as First-Line Treatment for Advanced or Metastatic Non-Squamous NSCLC Patients With EGFR Exon 20 Insertion Mutation: An Open-Label, Single-Arm, Phase II Trial [NCT05751187]Phase 254 participants (Anticipated)Interventional2023-06-27Recruiting
A Phase II Study of Breast Cancer Treatment Using Weekly Carboplatin + Paclitaxel With Pertuzumab + Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting [NCT02436993]Phase 2120 participants (Actual)Interventional2015-04-30Active, not recruiting
A Phase II Study of Endostar, Paclitaxel/Carboplatin and Radiotherapy in Patients With Non-resectable Locally Advanced Non-small Cell Lung Cancer [NCT01158144]Phase 2134 participants (Anticipated)Interventional2009-10-31Recruiting
A Phase 1 Study of ABT-888 (Veliparib) in Combination With Weekly Carboplatin and Paclitaxel in Advanced Solid Tumors [NCT01281150]Phase 122 participants (Actual)Interventional2011-01-31Completed
Nab-Paclitaxel-based Re-induction Chemotherapy Followed by Response-stratified Chemoradiotherapy in Patients With Previously Treated Squamous Cell Carcinoma of the Head and Neck. [NCT01847326]Phase 148 participants (Actual)Interventional2013-03-26Active, not recruiting
A Randomized Phase II Study of Paclitaxel-carboplatin-bevacizumab With or Without Nitroglycerin Patches in Patients With Stage IV Non-squamous-non-small Cell Lung Cancer: NVALT12 [NCT01171170]Phase 2223 participants (Actual)Interventional2011-01-31Completed
Phase I Study of Trientine and Carboplatin in Patients With Advanced Malignancies [NCT01178112]Phase 156 participants (Actual)Interventional2010-07-31Completed
Multicenter, Randomized, Double-blind, Phase Ⅲ Clinical Study to Evaluate the Efficacy and Safety of TQB2450 Plus Chemotherapy（Cisplatin or Carboplatin+ 5-Fluorouracil (5-FU) ） Versus Placebo Plus Chemotherapy as First-Line Treatment in Patients With Recu [NCT03855384]Phase 3334 participants (Anticipated)Interventional2019-06-11Recruiting
An Open-label, Dose-escalation, Safety and Pharmacokinetics Phase I Study of Ombrabulin in Combination With Paclitaxel and Carboplatin Every 3 Weeks in Patients With Advanced Solid Tumors [NCT01293630]Phase 118 participants (Actual)Interventional2011-01-31Completed
A Prospective, Open-label,Multicenter Phase II Study of Neoadjuvant Pyrotinib Plus Trastuzumab and Chemotherapy in Women With HER2 Positive Early Stage or Locally Advanced Breast Cancer [NCT03847818]268 participants (Anticipated)Interventional2019-03-01Not yet recruiting
A Phase II Trial of Bevacizumab With Carboplatin and Weekly Paclitaxel as First-Line Treatment in Epithelial Ovarian, Primary Peritoneal, and Fallopian Tube Carcinoma [NCT01097746]Phase 233 participants (Actual)Interventional2010-04-14Completed
A Phase I Evaluation of Extended Field Radiation Therapy With Concomitant Cisplatin Chemotherapy Followed by Paclitaxel and Carboplatin Chemotherapy in Women With Cervical Carcinoma Metastatic to the Para-aortic Lymph Nodes [NCT01295502]Phase 145 participants (Anticipated)Interventional2011-04-04Active, not recruiting
A Phase IIB/III Randomized, Double-blind, Placebo Controlled Study Comparing First Line Therapy With or Without TG4010 Immunotherapy Product in Patients With Stage IV Non-Small Cell Lung Cancer (NSCLC) [NCT01383148]Phase 2/Phase 3222 participants (Actual)Interventional2012-04-30Terminated
A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors [NCT01297452]Phase 145 participants (Actual)Interventional2011-02-15Completed
Induction Pemetrexed and Cisplatin Followed by Pemetrexed as Maintenance vs Carboplatin-paclitaxel and Bevacizumab Followed by Bevacizumab as Maintenance:Multicenter Randomized Phase III Study in Patients With Advanced Non-Squamous Non Small-cell Lung Can [NCT01303926]Phase 3118 participants (Anticipated)Interventional2010-01-31Active, not recruiting
FDG-PET Based Chemotherapy Selection for Metastatic Non-Small Cell Lung Cancer [NCT00564733]Phase 255 participants (Actual)Interventional2007-10-31Completed
A Phase 2, Open-Label Study of Acalabrutinib in Combination With R-ICE For Relapsed or Refractory Non-Germinal Center Diffuse Large B Cell Lymphoma, Transformed Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia or Transformed Marginal Zone Lymphoma [NCT04189952]Phase 22 participants (Actual)Interventional2020-09-22Terminated(stopped due to Investigator Decision)
A Phase 2, Open-Label, Randomized, Multicenter Study to Evaluate the Efficacy and Safety of Pemigatinib Plus Pembrolizumab Versus Pemigatinib Alone Versus Standard of Care as First-Line Treatment for Metastatic or Unresectable Urothelial Carcinoma in Cisp [NCT04003610]Phase 27 participants (Actual)Interventional2020-05-14Terminated(stopped due to The reason this study was terminated was due to a business decision. There were no safety concerns that contributed to this decision.)
A Phase 3 Randomized, Double-Blind, Placebo-controlled Trial of Pembrolizumab (MK-3475/SCH900475) in Combination With Etoposide/Platinum (Cisplatin or Carboplatin) for the First-line Treatment of Subjects With Extensive Stage Small Cell Lung Cancer (KEYNO [NCT03066778]Phase 3453 participants (Actual)Interventional2017-05-02Completed
Trimodality Protocol for the Treatment of Locally Advanced, Potentially Resectable Non-Small Cell Lung Cancer Targeting [NCT00043108]Phase 219 participants (Actual)Interventional2002-07-31Completed
The Maximum Tolerated Dose and to Evaluate Safety and Efficacy of Belinostat (PXD-101) in Combination With Paclitaxel Plus Carboplatin in Chemotherapy-Naive Patients With Stage IV Non-Small-Cell Lung Cancer (NSCLC) [NCT01310244]Phase 1/Phase 223 participants (Actual)Interventional2010-12-31Completed
A Multicenter Phase II Trial of Neoadjuvant JS001, or JS001 in Combination With Chemotherapy in Resectable NSCLC. [NCT03623776]Phase 280 participants (Anticipated)Interventional2019-02-01Active, not recruiting
Randomized Phase III Trial of Doxorubicin/Cisplatin/Paclitaxel and G-CSF Versus Carboplatin/Paclitaxel in Patients With Stage III &Amp; IV or Recurrent Endometrial Cancer [NCT00063999]Phase 31,381 participants (Actual)Interventional2003-08-25Completed
A Phase II Trial of Paclitaxel and Carboplatin in the Treatment of Hormone-Refractory Prostate Cancer (HRPC) [NCT00049257]Phase 258 participants (Actual)Interventional2002-10-31Completed
Phase II Study of Erlotinib Plus Carboplatin and Paclitaxel in Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma [NCT00059787]Phase 256 participants (Actual)Interventional2003-04-30Completed
Multicenter Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed By Docetaxel (AC-T) With Doxorubicin and Cyclophosphamide Followed By Docetaxel and Trastuzumab (Herceptin)(AC-TH) and With Docetaxel, Carboplatin and Trastuzumab ( [NCT00021255]Phase 33,222 participants (Actual)Interventional2001-04-30Completed
A Phase I/II Dose Intensification Study Using Three Dimensional Conformal Radiation Therapy And Concurrent Chemotherapy For Patients With Inoperable, Non-Small Cell Lung Cancer [NCT00023673]Phase 1/Phase 263 participants (Actual)Interventional2001-07-31Completed
Phase II Study of Postoperative Concurrent Chemoradiotherapy for Esophageal Squamous Cell Carcinoma (ESO- Shanghai 17) [NCT04764227]Phase 270 participants (Actual)Interventional2020-05-30Active, not recruiting
Phase II, Single-Arm Study Of Carboplatin, Weekly Taxane, And Ramucirumab In Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) After Progressive Disease On Maintenance Pemetrexed And/Or Pembrolizumab [NCT04332367]Phase 259 participants (Anticipated)Interventional2020-08-01Recruiting
A Non-Randomized Phase Ib-II Protocol of Paclitaxel, Carboplatin and the Dual PI3K/mTOR Kinase Inhibitor, PF-05212384, for Patients With Advanced, or Metastatic Non-Small Cell Carcinoma of the Lung [NCT02920450]Phase 1/Phase 23 participants (Actual)Interventional2017-09-25Terminated(stopped due to Slow accrual)
A Phase 1 Study to Evaluate the Effects of Rifampin on Pharmacokinetics of Pevonedistat in Patients With Advanced Solid Tumors [NCT03486314]Phase 120 participants (Actual)Interventional2018-08-13Completed
Tandem High-Dose Chemotherapy With Autologous Stem Cell Rescue for Poor-Prognosis Germ Cell Cancer [NCT00002931]Phase 248 participants (Actual)Interventional1997-02-28Completed
A Phase Ib Dose Escalation Study of MK-4827 in Combination With Carboplatin, Carboplatin/Paclitaxel and Carboplatin/Liposomal Doxorubicin in Patients With Advanced Solid Tumors [NCT01110603]Phase 112 participants (Actual)Interventional2010-07-31Terminated
Atezolizumab in Combination With Bevacizumab, Carboplatin and Pemetrexed for EGFR-mutant Metastatic Non-small Cell Lung Cancer Patients After Failure of EGFR Tyrosine Kinase Inhibitors: a Single Arm Phase 2 Study [NCT03647956]Phase 240 participants (Anticipated)Interventional2018-10-01Recruiting
Sensitivity Detection and Drug Resistance Mechanism of Breast Cancer Therapeutic Drugs Based on Organ-like Culture [NCT03925233]300 participants (Anticipated)Observational2019-01-02Enrolling by invitation
A Phase III Randomized Multicenter Study,Comparing an Induction Chemotherapy Followed by Irradiation and Concurrent Erbitux Versus Chemoradiotherapy for Patients With Locoregional Advanced Head and Neck Cancers [NCT01233843]Phase 3370 participants (Actual)Interventional2009-05-18Completed
A Phase Ib/II Multicenter, Randomized, Open Label Trial to Compare Tepotinib (MSC2156119J) Combined With Gefitinib Versus Chemotherapy as Second-Line Treatment in Subjects With MET Positive, Locally Advanced or Metastatic NSCLC Harboring EGFR Mutation and [NCT01982955]Phase 1/Phase 288 participants (Actual)Interventional2013-12-23Completed
A Phase 1 Study of Neoadjuvant Chemotherapy With the Gamma Secretase Inhibitor RO4929097 in Combination With Paclitaxel and Carboplatin in Patients With Clinical Stage II-III Triple Negative Breast Cancer [NCT01238133]Phase 114 participants (Actual)Interventional2010-12-31Terminated
A Phase 0 Clinical Trial of Microdosing Carboplatin and Molecular Profiling for Chemoresistance [NCT01261299]Early Phase 121 participants (Actual)Interventional2010-12-31Terminated(stopped due to Contract ended)
A Multicenter Phase II Trial of Neoadjuvant IBI308, Bevacizumab, Plus Pemetrexed and Carboplatin Followed by Surgery in Patients With Unresectable Stage III Non-Small Cell Lung Cancer [NCT03872661]Phase 236 participants (Anticipated)Interventional2019-03-01Recruiting
A Randomized Phase II Study Evaluating Pathologic Response Rates Following Pre-operAtive Non-Anthracycline Chemotherapy, Durvalumab (MEDI4736) +/- RAdiation Therapy (RT) in Triple Negative Breast Cancer (TNBC): The PANDoRA Study. [NCT03872505]Phase 20 participants (Actual)Interventional2022-07-31Withdrawn(stopped due to lack of funding)
Randomized Controlled Trial Comparing Concurrent Chemoradiation Versus Concurrent Chemoradiation Followed by Adjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients [NCT02036164]Phase 3500 participants (Anticipated)Interventional2014-01-31Recruiting
Efficacy and Safety of Tunlametinib Capsules Versus Combination Chemotherapy of Investigator's Choice in Advanced NRAS-mutant Melanoma Patients Who Had Previously Received Immunotherapy [NCT06008106]Phase 3165 participants (Anticipated)Interventional2023-09-22Not yet recruiting
A Randomized, Controlled, Multi-center Phase III Clinical Study of AK112 Combined With Chemotherapy Versus PD-1 Inhibitor Combined With Chemotherapy as First-line Treatment for Locally Advanced or Metastatic Squamous Non-small Cell Lung Cancer [NCT05840016]Phase 3396 participants (Anticipated)Interventional2023-08-17Recruiting
Phase 2 Study of Weekly Paclitaxel Plus Carboplatin in Preoperative Treatment of Breast Cancer Patients [NCT01203267]Phase 2108 participants (Actual)Interventional2007-12-31Completed
A Phase 3 Study of Pembrolizumab in Combination With Pemetrexed/Platinum (Carboplatin or Cisplatin) Followed by Pembrolizumab and Maintenance Olaparib vs Maintenance Pemetrexed in the First-Line Treatment of Participants With Metastatic Nonsquamous Non-Sm [NCT03976323]Phase 31,005 participants (Actual)Interventional2019-06-28Active, not recruiting
A Randomized Phase 3, Double-Blind Study of Chemotherapy With or Without Pembrolizumab Followed by Maintenance With Olaparib or Placebo for the First-Line Treatment of BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (KEYLYNK-001 / ENGOT-ov43 / G [NCT03740165]Phase 31,367 participants (Actual)Interventional2018-12-18Active, not recruiting
A Phase III Randomized, Controlled Clinical Trial of Pembrolizumab With or Without Platinum-Based Combination Chemotherapy Versus Chemotherapy in Subjects With Advanced or Metastatic Urothelial Carcinoma [NCT02853305]Phase 31,010 participants (Actual)Interventional2016-09-15Completed
Women's Triple-Negative First-Line Study: A Phase II Trial of Panitumumab, Carboplatin and Paclitaxel (PaCT) in Patients With Localized Triple-Negative Breast Cancer (TNBC) With Tumors Predicted Insensitive to Standard Neoadjuvant Chemotherapy [NCT02593175]Phase 244 participants (Actual)Interventional2016-08-26Active, not recruiting
An Open-Label Randomized Phase II Trial Comparing Gemcitabine and Carboplatin With and Without P276-00 in Subjects With Metastatic Triple Negative Breast Cancer, With a Phase I Run-in of Escalating Dose of P276-00 Added to Gemcitabine and Carboplatin [NCT01333137]Phase 111 participants (Actual)Interventional2011-08-31Terminated
The Randomized,Open, Multicenter Phase III Study to Compare the Effectiveness and Safety of Nab-Paclitaxel Versus Paclitaxel Plus Carboplatin First-Line Therapy Advanced Non Small Cell Lung Cancer Squamous Cell Carcinoma [NCT03262948]Phase 3388 participants (Anticipated)Interventional2017-12-01Not yet recruiting
Phase II Trial of Carboplatin/Paclitaxel and Cetuximab, Followed by Carboplatin/Paclitaxel/Cetuximab and Erlotinib, With Correlative Studies in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck. [NCT01316757]Phase 224 participants (Actual)Interventional2011-02-16Completed
AssessinG Efficacy of Carboplatin and ATezOlizumab in Metastatic Lobular Breast Cancer: GELATO-trial [NCT03147040]Phase 223 participants (Actual)Interventional2017-11-02Terminated(stopped due to At interim analysis insufficient benefit was observed to continu the study)
A Randomized, Open-label Study to Explore the Correlation of Biomarkers With Response Rate in Chemo-naive Patients With Advanced or Recurrent Non-squamous Non-small Cell Lung Cancer Who Receive Treatment With Avastin in Addition to Carboplatin-based Chemo [NCT00700180]Phase 2303 participants (Actual)Interventional2008-09-30Completed
Oral Navelbine Carboplatin Versus Gefitinib Neoadjuvant Therapy for Resectable EGFR Mutation Positive Stage Ⅱ-ⅢA NSCLC, Prospective, Randomized, Multicenter, Phase Ⅲ Clinical Trial [NCT03203590]Phase 3590 participants (Anticipated)Interventional2017-09-30Not yet recruiting
An Open Label, Multicenter, Phase 1b/2 Study of Rebastinib (DCC-2036) in Combination With Carboplatin to Assess Safety, Tolerability, and Pharmacokinetics in Patients With Advanced or Metastatic Solid Tumors [NCT03717415]Phase 1/Phase 2117 participants (Anticipated)Interventional2019-01-02Active, not recruiting
Multi-center, Randomized Controlled, Phase III Trials to Evaluate the Safety and Effectiveness After Cycles Reduction of Neoadjuvant Chemotherapy for Advanced Epithelial Ovarian, Fallopian and Primary Peritoneal Cancer [NCT03693248]Phase 3298 participants (Anticipated)Interventional2018-12-19Recruiting
Atezolizumab in Combination With Neoadjuvant Chemotherapy and Interval Cytoreductive Surgery for Patients With Newly-Diagnosed Advanced-Stage Epithelial Ovarian Cancer [NCT03394885]Phase 1/Phase 218 participants (Actual)Interventional2018-06-19Completed
A Phase II Randomised, Open-label Study of Gemcitabine/Carboplatin First-line Chemotherapy in Combination With or Without the Antisense Oligonucleotide Apatorsen (OGX-427) in Advanced Squamous Cell Lung Cancers [NCT02423590]Phase 2140 participants (Anticipated)Interventional2014-06-30Active, not recruiting
A Phase 2 Study of Icotinib With Concurrent Radiotherapy vs. Pemetrexed+ Carboplatin With Concurrent Radiotherapy in Unresectable Stage III Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor ( EGFR) Mutation [NCT02407366]Phase 280 participants (Anticipated)Interventional2014-12-31Recruiting
A Randomized Open-Label Phase III Trial of Pembrolizumab Versus Platinum Based Chemotherapy in 1L Subjects With PD-L1 Strong Metastatic Non-Small Cell Lung Cancer [NCT02142738]Phase 3305 participants (Actual)Interventional2014-08-25Completed
Exploiting Metformin Plus/Minus Cyclic Fasting Mimicking Diet (FMD) to Improve the Efficacy of First Line Chemo-immunotherapy in Advanced LKB1-inactive Lung Adenocarcinoma [NCT03709147]Phase 264 participants (Anticipated)Interventional2018-10-30Recruiting
A Phase II Trial of Pemetrexed and Cisplatin or Carboplatin in Combination With TTFields (150 kHz) as First-line Treatment in Malignant Pleural Mesothelioma [NCT02397928]Phase 282 participants (Actual)Interventional2015-02-28Completed
Induction Therapy With Docetaxel, Cisplatin, 5-Fluoro Uracil and Pembrolizumab in Untreated Locally-advanced Unresectable Squamous Cell Head and Neck Carcinoma (Pembrolizumab and Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma. PICH Study) [NCT03114280]Phase 1/Phase 20 participants (Actual)Interventional2019-03-12Withdrawn(stopped due to MSD would not able to support the study's continuation after protocol modifications required by ANSM through dose de-escalation of pembrolizumab)
A Randomized, Double-blind, Multicenter Phase III Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy Versus Placebo Combined With Chemotherapy as First-line Treatment in Subjects With Advanced Non-squamous Cell Non-small Cell Lung Cancer [NCT04439890]Phase 3369 participants (Anticipated)Interventional2019-08-08Recruiting
Official Title: A Phase II Multicenter, Open Label, Non-randomized Study of Neoadjuvant and Adjuvant Treatment With IPH5201 and Durvalumab in Patients With Resectable, Early-stage (II to IIIA) Non-Small Cell Lung Cancer (MATISSE) [NCT05742607]Phase 270 participants (Anticipated)Interventional2023-06-23Recruiting
A Phase Ⅱ Clinical Study of Combination Therapy of SKB264 in Patients With Advanced or Metastatic Non-small Cell Lung Cancer [NCT05351788]Phase 2110 participants (Anticipated)Interventional2022-05-20Recruiting
A Phase 3 Study to Evaluate Zimberelimab (AB122) Combined With AB154 in Front-Line, PD-L1-High, Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT04736173]Phase 3750 participants (Anticipated)Interventional2021-02-08Recruiting
Phase III Randomized Trial of Atezolizumab in Elderly Patients With Advanced Non-Small-Cell Lung Cancer and Receiving Monthly Carboplatin With Weekly Paclitaxel Chemotherapy [NCT03977194]Phase 3500 participants (Anticipated)Interventional2019-07-23Active, not recruiting
A Phase Ib/II, Open-Label, Multicentre Study to Assess Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of AZD9150 Plus Durvalumab Alone or in Combination With Chemotherapy in Patients With Advanced, Solid Tumours and Subsequent [NCT03421353]Phase 176 participants (Actual)Interventional2018-02-07Active, not recruiting
Phase 1b Dose-Finding Study of Niraparib, TSR-022, Bevacizumab, and Platinum-Based Doublet Chemotherapy in Combination With TSR-042 in Patients With Advanced or Metastatic Cancer [NCT03307785]Phase 158 participants (Actual)Interventional2017-10-12Active, not recruiting
Chemotherapy-free Trastuzumab and Pertuzumab in HER2-positive (Human Epidermal Receptor) Breast Cancer: FDG-PET Response-adapted Strategy. The PHERGain Study [NCT03161353]Phase 2377 participants (Actual)Interventional2017-06-26Completed
Moving PD-1 Blockade With Pembrolizumab Into Concurrent Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer [NCT02621398]Phase 123 participants (Actual)Interventional2016-08-04Active, not recruiting
A Phase 1/2, Open-Label, Safety, Tolerability, and Efficacy Study of Epacadostat in Combination With Pembrolizumab and Chemotherapy in Subjects With Advanced or Metastatic Solid Tumors (ECHO-207/KEYNOTE-723) [NCT03085914]Phase 1/Phase 270 participants (Actual)Interventional2017-05-02Completed
Randomized Phase II Study of Pre-operative Chemoradiotherapy +/- Panitumumab (IND #110152) Followed by Consolidation Chemotherapy in Potentially Operable Locally Advanced (Stage IIIA, N2+) Non-Small Cell Lung Cancer [NCT00979212]Phase 271 participants (Actual)Interventional2011-02-28Completed
Neoadjuvant Phase II Study of Pembrolizumab And Carboplatin Plus Docetaxel in Triple Negative Breast Cancer [NCT03639948]Phase 2121 participants (Actual)Interventional2018-09-04Active, not recruiting
Evaluation of PEGylated Doxorubicin Hydrochloride Liposome Injection(Duomeisu®) Combined With Carboplatin Versus Paclitaxel Plus Carboplatin in the First-line Treatment of Epithelial Ovarian Cancer: A Randomized, Open, Multicenter Clinical Study [NCT03794778]Phase 4396 participants (Anticipated)Interventional2019-03-19Active, not recruiting
A Prospective, One-arm Open Clinical Trial of Apatinib Combined With Albumin Paclitaxel and Carboplatin as a Neoadjuvant Therapy for the Safety and Efficacy of Triple-negative Breast Cancer [NCT03650738]Phase 260 participants (Anticipated)Interventional2018-09-01Recruiting
A Phase I Trial of Preoperative Carboplatin or Cisplatin and Pemetrexed With Thoracic Radiation Therapy Followed by Lobectomy in Resectable Stage III Patients With Non-Squamous Non Small Cell Lung Cancer (NSCLC) [NCT01373463]Phase 148 participants (Actual)Interventional2011-05-31Terminated(stopped due to Investigator left site)
A Phase II, Prospective Clinical Study to Evaluate the Efficacy and Safety of Tislelizumab Plus Chemotherapy as First-Line Treatment in Patients With Brain Metastases of Squamous Non-small Cell Lung Cancer [NCT05207904]Phase 241 participants (Anticipated)Interventional2021-06-17Recruiting
The Safety and Efficacy of Rh-Endostatin (Endostar®) Continuous Intravenous Infusion in Combination With Docetaxel/Carboplatin or Pemetrexed/Carboplatin (DC/PC) Regimens for Untreated Stage IIIB/IV Non-small-cell Lung Cancer (NSCLC) [NCT03706703]Phase 250 participants (Anticipated)Interventional2018-10-01Recruiting
A Multicenter Phase II Trial of Carboplatin, Pemetrexed, and Bevacizumab Followed By Pemetrexed and Bevacizumab Maintenance Therapy in Patients With a Light or Never Smoking History [NCT01344824]Phase 238 participants (Actual)Interventional2010-03-31Completed
Phase Ia/Ib and Potential Phase IIa Study of the Safety and Pharmacokinetics of NOX66 Both as a Monotherapy and in Combination With Carboplatin in Patients With Refractory Solid Tumours [NCT02941523]Phase 1/Phase 219 participants (Actual)Interventional2017-03-03Completed
Thoracic Radiotherapy Plus Maintenance Durvalumab After First Line Carboplatin and Etoposide Plus Durvalumab in Extensive-stage Disease Small Cell Lung Cancer (ED-SCLC). A Multicenter Single Arm Open Label Phase II Trial. [NCT04472949]Phase 246 participants (Actual)Interventional2021-06-25Active, not recruiting
A Phase I/II Study of Anlotinib Combined With Platinum-based Chemotherapy as the First-line Treatment of Patients With Locally Advanced or Advanced Non-Small Cell Lung Cancer [NCT03636685]Phase 1/Phase 260 participants (Anticipated)Interventional2018-08-15Not yet recruiting
A Prospective, Open-label, Non-inferiority Study to Evaluate Injectable Albumin-bound Paclitaxel Versus Docetaxel for the Adjuvant Treatment of Breast Cancer [NCT05420467]Phase 42,413 participants (Anticipated)Interventional2022-07-10Recruiting
Randomized Phase II Study of 3 vs 6 Courses of Neoadjuvant Carboplatin-paclitaxel Chemotherapy in Stage IIIC or IV Epithelial Ovarian Cancer, Fallopian Tube Carcinoma or Primary Peritoneal Carcinoma [NCT02125513]Phase 2129 participants (Actual)Interventional2014-01-31Active, not recruiting
To Study the Factors Affecting Treatment Responses in Patients With Uterine Cervical Carcinoma Undergoing Neoadjuvant Chemotherapy [NCT05384366]Phase 333 participants (Actual)Interventional2020-08-01Completed
InterAACT - An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin Plus 5-Fluorouracil Versus Carboplatin Plus Weekly Paclitaxel in Patients With Inoperable Locally Recurrent or Metastatic Disease [NCT02560298]Phase 291 participants (Actual)Interventional2016-08-23Active, not recruiting
An Open-label, Single-group, Multi-center, Phase II Clinical Trial Evaluating the Effect of Maintenance DCVAC/OvCa After Standard-of-care Therapy in Women With First Relapse of Platinum-sensitive Epithelial Ovarian Cancer [NCT03657966]Phase 233 participants (Actual)Interventional2017-11-23Completed
A Randomized, Double-blind, Placebo-Controlled, Phase 3 Study to Assess the Efficacy and Safety of Weekly Farletuzumab (MORAb-003) in Combination With Carboplatin and Taxane in Subjects With Platinum-sensitive Ovarian Cancer in First Relapse [NCT00849667]Phase 31,100 participants (Actual)Interventional2009-04-16Terminated(stopped due to Lack of efficacy)
A Phase II Study of Pembrolizumab and Dynamic PD-L1 Expression in Extensive Stage Small Cell Lung Cancer (SCLC) [NCT02934503]Phase 25 participants (Actual)Interventional2017-01-23Terminated(stopped due to This study was terminated as the standard of care for small cell lung cancer changed in 2018 to include immunotherapy in the front line setting, making this study no longer clinically relevant.)
Randomized Phase II Trial Evaluating the Optimal Sequencing of PD-1 Inhibition With Pembrolizumab (MK-3475) and Standard Platinum-based Chemotherapy in Patients With Chemotherapy Naive Stage IV Non-small Cell Lung Cancer [NCT02591615]Phase 291 participants (Actual)Interventional2016-03-31Completed
Randomized Phase Ⅲ Trial Comparing Dose-dense Epirubicin and Cyclophosphamide Followed by Paclitaxel With Paclitaxel Plus Carboplatin as Adjuvant Therapy for Triple-negative Breast Cancer. [NCT01378533]Phase 3100 participants (Anticipated)Interventional2011-05-31Recruiting
A Phase I, Open-Label, Dose-Seeking Study of AZD2171 Given Daily Orally in Combination With Standard Chemotherapy Regimens (CT) in Patients With Advanced Incurable Non-Small Cell Lung Cancer (NSCLC) or Colorectal Cancer or Other Tumor Types Suitable for T [NCT00107250]Phase 150 participants (Actual)Interventional2005-01-21Completed
Neoadjuvant Carboplatin in Triple Negative Breast Cancer - A Prospective Phase II Study (NACATRINE Trial). [NCT02978495]Phase 2154 participants (Actual)Interventional2017-05-17Completed
Phase II Trial Of Induction Chemotherapy Followed By Attenuated Chemoradiotherapy For Locally Advanced Head And Neck Squamous Cell Carcinoma Associated With Human Papillomavirus (HPV) [NCT02048020]Phase 226 participants (Actual)Interventional2013-12-26Completed
A Pilot Study of Dose-dense (Biweekly) Carboplatin Plus Paclitaxel With or Without Trastuzumab as Neoadjuvant Treatment for Breast Cancer [NCT02059876]Phase 260 participants (Anticipated)Interventional2013-11-30Recruiting
DOSE FINDING STUDY OF PF-05212384 WITH PACLITAXEL AND CARBOPLATIN IN PATIENTS WITH ADVANCED SOLID TUMOR [NCT02069158]Phase 117 participants (Actual)Interventional2014-04-30Completed
Pharmacokinetics of Carboplatin After Adjusted Dosing for High BMI, Low Serum Creatinine, and Maximal Renal Function [NCT02103244]Phase 424 participants (Anticipated)Interventional2014-09-30Not yet recruiting
A Phase I Study of the Combination of Carboplatin, Docetaxel, and Increasing Doses of Sublingual Anvirzel (Nerium Oleander) in Advance Non-Small Cell Lung Cancer [NCT01562301]Phase 10 participants (Actual)Interventional2014-06-30Withdrawn
Ocular Conservative Treatment for Retinoblastoma: Efficacy of the New Management Strategies and Visual Outcome - RETINO 2018 [NCT04681417]Phase 2/Phase 3225 participants (Anticipated)Interventional2021-03-25Recruiting
Phase III Randomized Trial of Pleurectomy/Decortication Plus Systemic Therapy With or Without Adjuvant Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) for Malignant Pleural Mesothelioma (MPM) [NCT04158141]Phase 316 participants (Actual)Interventional2020-01-29Terminated(stopped due to Permanent Administrative Closure)
A Phase 1, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability Pharmacokinetics Immunogenicity, and Antitumor Activity of MEDI5752 in Subjects With Advanced Solid Tumors. [NCT03530397]Phase 1396 participants (Anticipated)Interventional2018-04-24Recruiting
Metabolic and Molecular Response Evaluation for the Individualization of Therapy in Adenocarcinomas of the Gastroesophageal Junction [NCT02287129]Phase 275 participants (Actual)Interventional2014-12-05Completed
A Phase III Multicenter, Randomized Study of Oral LDK378 Versus Standard Chemotherapy in Previously Untreated Adult Patients With ALK Rearranged (ALK-positive), Stage IIIB or IV, Non-squamous Non-small Cell Lung Cancer [NCT01828099]Phase 3376 participants (Actual)Interventional2013-07-09Active, not recruiting
A Phase III, Randomized, Double-blinded, Multicenter Study of AK105 Combined With Carboplatin and Pemetrexed vs Placebo Combined With Carboplatin and Pemetrexed as First-line Therapy in Patients With Metastatic Nonsquamous Non-small Cell Lung Cancer [NCT03866980]Phase 3164 participants (Actual)Interventional2018-11-27Active, not recruiting
A Phase II Randomized Study of OSI-774 (Erlotinib) (NSC #718781) With or Without Carboplatin/Paclitaxel in Patients With Previously Untreated Adenocarcinoma of the Lung Who Never Smoked or Were Former Light Smokers [NCT00126581]Phase 2188 participants (Actual)Interventional2005-08-15Completed
[NCT01342237]Phase 233 participants (Anticipated)Interventional2011-03-31Recruiting
A Prospective Phase II Study of Involved Field Elective Volume De-Intensification for Oropharyngeal and Laryngeal Squamous Cell Carcinoma Treated With Intensity Modulated Radiation Therapy [NCT03067610]Phase 272 participants (Actual)Interventional2017-01-20Completed
Phase I/II Study of Induction Chemotherapy With Weekly RAD001, Carboplatin and Paclitaxel in Unresectable or Inoperable Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC) [NCT01333085]Phase 1/Phase 249 participants (Actual)Interventional2009-10-31Completed
Efficacy of Carboplatin Administered Concomitantly With Radiation and Isotretinoin as a Pro-Apoptotic Agent in Other Than Average Risk Medulloblastoma/PNET Patients [NCT00392327]Phase 3379 participants (Actual)Interventional2007-03-26Active, not recruiting
The Efficacy and Safety of Osimertinib Plus Carboplatin and Pemetrexed Versus Osimertinib Monotherapy in Metastatic EGFRm NSCLC Patients With EGFRm Persistence in ctDNA at 3 Weeks After 1L Osimertinib: A Multicenter, Randomized Controlled Study [NCT04769388]Phase 2150 participants (Anticipated)Interventional2021-12-28Recruiting
Safety and Efficacy of Combination Chemotherapy With Pazopanib in Children and Adolescents With Relapsed/Refractory Solid Tumors [NCT03628131]Phase 1/Phase 246 participants (Anticipated)Interventional2018-10-31Not yet recruiting
Anlotinib-based Combination as First-line Treatment in Advanced Non-small Cell Lung Cancer: a Single Center, Three Arms and Exploratory Study [NCT03628521]Phase 180 participants (Anticipated)Interventional2018-07-20Recruiting
Chemotherapy Toxicity in Elderly Women With Ovarian, Primary Peritoneal or Fallopian Tube Cancer [NCT01366183]290 participants (Anticipated)Observational2011-08-15Active, not recruiting
Phase II Neoadjuvant Trial With Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients [NCT01372579]Phase 230 participants (Anticipated)Interventional2011-08-31Active, not recruiting
Neoadjuvant or Adjuvant Chemotherapy Without Anthracyclines for Elderly Patients Diagnosed With HER2 Positive Breast Cancer [NCT02102438]0 participants (Actual)Interventional2014-04-30Withdrawn(stopped due to No financial support aproved)
A Phase I Study of Mebendazole for the Treatment of Pediatric Gliomas [NCT01837862]Phase 1/Phase 236 participants (Anticipated)Interventional2013-10-22Recruiting
Randomized Phase II Trial of PET Scan-Directed Combined Modality Therapy in Esophageal Cancer [NCT01333033]Phase 2257 participants (Actual)Interventional2011-07-31Completed
Carboplatin Periocular Injection in the Treatment for Retinoblastoma--A Single Center, Randomized Study to Evaluate the Efficacy of Carboplatin in Subjects With Retinoblastoma [NCT02137928]Phase 350 participants (Anticipated)Interventional2006-01-31Recruiting
A Study to Evaluate the Safety of Transient Opening of the Blood-Brain Barrier by Low Intensity Pulsed Ultrasound With the SonoCloud Implantable Device in Patients With Recurrent Glioblastoma Before Chemotherapy Administration [NCT02253212]Phase 1/Phase 227 participants (Actual)Interventional2014-07-31Completed
Recombinant Human Endostatin in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer With Negative Driver Gene: a Multicenter, Single-Arm Trial [NCT05574998]Phase 2100 participants (Anticipated)Interventional2021-02-01Recruiting
Randomized, Double-Blind, Multicenter, Phase 2 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT01560104]Phase 2160 participants (Actual)Interventional2012-02-29Completed
A Phase I/II Study of MK-3475 (SCH900475) in Combination With Chemotherapy or Immunotherapy in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Carcinoma [NCT02039674]Phase 1/Phase 2267 participants (Actual)Interventional2014-02-21Completed
Toripalimab Plus Etoposide and Platinum-based Chemotherapy in First-line Treatment of Locally Advanced or Metastatic Genitourinary Small Cell Carcinoma：A Multicenter, Prospective, Open Label, Single-arm, Phase II Study [NCT05760053]Phase 233 participants (Anticipated)Interventional2023-02-18Recruiting
Randomized Trial of Surgery With or Without Paclitaxel Plus Carboplatin as Neoadjuvant or Adjuvant Chemotherapy in Patients With Operable, Non-small-cell Lung Cancer [NCT00913705]Phase 3624 participants (Anticipated)Interventional1999-09-30Completed
Phase I Dose Escalation Trial to Determine the Maximum Tolerated Dose of BIBF 1120 in Combination With Carboplatin and Pegylated Liposomal Doxorubicin (PLD) in Patients With a First, Second or Third Platinum Sensitive Relapse of Advanced Epithelial Ovaria [NCT01314105]Phase 119 participants (Actual)Interventional2011-03-31Completed
An International Multicentre Open Label Randomised Phase II Advanced Anal Cancer Trial Comparing Cisplatin Plus 5 FU vs Carboplatin Plus Weekly Paclitaxel in Patients With Inoperable Locally Recurrent or Metastatic Disease [NCT02051868]Phase 280 participants (Anticipated)Interventional2013-12-31Recruiting
Phase III, Multicenter, Open-label, Randomized Trial of Tarceva® vs Chemotherapy in Patients With Advanced NSCLC With Mutations in the TK Domain of the EGFR [NCT00446225]Phase 3174 participants (Actual)Interventional2007-02-28Completed
An Indian Multicentric Open Label Prospective Phase IV Study to Evaluate Safety and Efficacy of Trastuzumab in Her2 Positive, Node Positive or High Risk Node Negative Breast Cancer as Part of a Treatment Regimen Consisting of Doxorubicin, Cyclophosphamide [NCT02419742]Phase 4110 participants (Actual)Interventional2015-08-18Completed
Combination of Chemotherapy and Gefitinib as First-line Treatment of Patients With Advanced Lung Adenocarcinoma and Sensitive EGFR Mutations: a Randomised Controlled Trial [NCT02148380]121 participants (Actual)Interventional2014-05-31Completed
Carboplatin Chemotherapy and Involved Node Radiotherapy in Stage IIA/B Seminoma [NCT01593241]Phase 2115 participants (Anticipated)Interventional2012-06-15Active, not recruiting
LCI-LUN-NSC-SBRT-001: Phase II Prospective Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation and Adjuvant Immunotherapy for Locally-Advanced Non-Small Cell Lung Cancer [NCT03141359]Phase 261 participants (Actual)Interventional2017-05-12Active, not recruiting
An Open-label, Phase 2 Basket Study of SEA-CD40 Combination Therapies in Advanced Malignancies [NCT04993677]Phase 277 participants (Actual)Interventional2021-10-06Active, not recruiting
A Phase II Trial of Hypofractionated Intensity-Modulated Radiation Therapy (IMRT) Utilizing 2.5 Gy/Fraction to PET-avid Disease Combined With Carboplatin and Paclitaxel for Subjects With Stage IIIA or IIIB Non-Small Cell Lung Cancer [NCT03699033]Phase 20 participants (Actual)Interventional2018-10-01Withdrawn(stopped due to No patients available)
A Phase I Open Label Dose Escalation Study of Continuous Oral Treatment With BIBF 1120 Together With Paclitaxel and Carboplatin in Patients With Advanced Stage Non-small-cell Lung Cancer [NCT02182232]Phase 133 participants (Actual)Interventional2005-06-30Completed
Study Assessing the Effects of Chemotherapy in Advanced Esophagogastric Adenocarcinoma - Carboplatin, Docetaxel and Capecitabine (CTX) or Epirubicin, Oxaliplatin and Capecitabine: a Randomised Phase 2 Trial. [NCT02177552]Phase 298 participants (Anticipated)Interventional2014-06-30Active, not recruiting
A Phase I/II Safety, Pharmacodynamic, and Pharmacokinetic Study of Intravenously Administered PXD101 Plus Carboplatin or Paclitaxel or Both in Patients With Advanced Solid Tumours [NCT00421889]Phase 1/Phase 280 participants (Actual)Interventional2005-08-31Completed
A Phase 1 Dose-Escalation Study of ABT-888 (Veliparib) in Combination With Carboplatin in HER2 Negative Metastatic Breast Cancer [NCT01251874]Phase 144 participants (Actual)Interventional2010-11-16Completed
Randomized Phase Ⅲ Trial Comparing Dose-dense Epirubicin and Cyclophosphamide Followed by Paclitaxel With Paclitaxel Plus Carboplatin as Adjuvant Therapy for Triple-negative Breast Cancer With Homologous Recombination Repair Deficiency [NCT03876886]Phase 3200 participants (Anticipated)Interventional2019-02-22Recruiting
Phase I Study of Carboplatin, Pegylated Liposomal Doxorubicin (PLD) and Everolimus in Patients With Platinum-Sensitive Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Cancer in First Relapse [NCT01281514]Phase 121 participants (Actual)Interventional2010-12-14Completed
Randomized, Double-blind, Multicenter Two-Stage Adaptive Phase 3 Study of Intravenous Administration of REOLYSIN (Reovirus Type 3 Dearing) in Combination With Paclitaxel and Carboplatin Versus the Chemotherapy Alone in Patients With Metastatic or Recurren [NCT01166542]Phase 3167 participants (Actual)Interventional2010-06-30Completed
A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy Versus Standard of Care Platinum-Based Chemotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non Small-Cell Lung Can [NCT02542293]Phase 3953 participants (Actual)Interventional2015-11-03Active, not recruiting
An Open-label, Multicenter, Phase 1b Study of CNTO 888 (an Anti-CCL 2 Monoclonal Antibody) in Combination With Chemotherapies for the Treatment of Subjects With Solid Tumors [NCT01204996]Phase 153 participants (Actual)Interventional2010-05-31Completed
A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of GDC-0980 in Combination With Either Paclitaxel and Carboplatin (With or Without Bevacizumab) or Pemetrexed and Cisplatin in Patients With Solid Tumors [NCT01301716]Phase 175 participants (Actual)Interventional2011-09-30Completed
Anlotinib Combined With Pemetrexed And Carboplatin Followed by Maintenance Therapy With Anlotinib Plus Pemetrexed as the First-line Treatment in Patients With Advanced Nonsquamous NSCLC [NCT03790228]Phase 143 participants (Anticipated)Interventional2019-03-22Recruiting
A Randomized, Open-label, Three-arm, Multi-center Phase II Trial of Addition of DCVAC/OvCa to First Line Standard Chemotherapy in Women With Newly Diagnosed Epithelial Ovarian Carcinoma [NCT02107937]Phase 2136 participants (Actual)Interventional2013-11-30Completed
Phase II Study of SHR-1210(Anti-PD-1 Antibody) Combination With Apatinib Versus Pemetrexed and Carboplatin in Subjects With KRAS Mutant Stage IV Non-squamous Non-small Cell Lung Cancer [NCT03777124]Phase 2230 participants (Anticipated)Interventional2019-02-28Not yet recruiting
Cetuximab in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First Line Treatment of Subjects With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT00122460]Phase 3442 participants (Actual)Interventional2004-12-31Completed
Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab Plus Docetaxel and Carboplatin in Patients With HER2 Positive Early Stage or Locally Advanced Breast Cancer: a Single-arm, Ahead, Open-label Study [NCT03756064]100 participants (Anticipated)Interventional2019-08-01Recruiting
Phase 2 Study Of SU011248 As Consolidation Therapy In Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer [NCT00113516]Phase 284 participants (Actual)Interventional2005-09-30Completed
A Phase II Trial Of BAY 43-9006, A Novel Raf Kinase Inhibitor Plus Paclitaxel/Carboplatin In Women With Recurrent Platinum Sensitive Epithelial Ovarian, Peritoneal Or Fallopian Tube Cancer [NCT00096200]Phase 244 participants (Actual)Interventional2004-08-31Completed
Open-label, Phase 2 Study of Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Tusamitamab Ravtansine (SAR408701) Combined With Pembrolizumab and Platinum-based Chemotherapy With or Without Pemetrexed in Patients With CEACAM5 Positive Exp [NCT04524689]Phase 2215 participants (Anticipated)Interventional2020-10-26Recruiting
Phase Ib/II Study to Determine the Recommended Dose, Safety, and Preliminary Efficacy of Belinostat When Used in Combination With Carboplatin, Paclitaxel, and Bevacizumab in Patients With Untreated Non-small Cell Lung Cancer. [NCT01090830]Phase 1/Phase 27 participants (Actual)Interventional2010-04-30Terminated(stopped due to Principal Investigator has left institution. IND withdrawn.)
A Phase II Trial to Investigate Genetic Markers of Response to Pembrolizumab (MK-3475, SCH 900475) Combined With Chemotherapy as a First-line Treatment for Non-Small Cell Lung Cancer (KEYNOTE-782) [NCT03664024]Phase 2118 participants (Actual)Interventional2018-10-30Completed
The Efficacy and Safety of Apatinib Combined With Paclitaxel and Carbopatin Intensive Regimen in Neoadjuvant Therapy for Locally Advanced Triple-negative Breast Cancer :Single Arm, Phase II Clinical Trail [NCT03735082]Phase 229 participants (Anticipated)Interventional2018-11-01Recruiting
A Double-Blind, Randomized, Placebo-Controlled Phase III Trial of Carboplatin, Paclitaxel and Sorafenib Versus Carboplatin, Paclitaxel and Placebo in Patients With Unresectable Locally Advanced or Stage IV Melanoma [NCT00110019]Phase 3823 participants (Actual)Interventional2005-06-30Completed
Phase III Open Label First Line Therapy Study of Tislelizumab With Chemotherapy Versus Chemotherapy in Untreated Advanced Non-Squamous Non-Small Cell Lung Cancer(NSCLC) [NCT03663205]Phase 3334 participants (Actual)Interventional2018-07-23Completed
Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Human Papilloma Virus Associated Oropharyngeal Carcinoma [NCT05491512]Phase 2121 participants (Anticipated)Interventional2022-08-04Recruiting
Neoadjuvant Sintilimab Plus Chemotherapy in EGFR-mutant Stage II-IIIB NSCLC: A Single-arm, Open-label Prospective Study [NCT05244213]Phase 235 participants (Anticipated)Interventional2022-06-04Recruiting
A Phase II, Prospective, Single Arm Trial of Cadonilimab in Combination With Bevacizumab and Standard Chemotherapy as First Line Therapy in Unresectable Pleural Mesothelioma [NCT05930665]Phase 238 participants (Anticipated)Interventional2023-07-31Not yet recruiting
Phase 1b Single Arm, Open-label Trial of RYZ101 in Combination With Carboplatin + Etoposide + Atezolizumab in Subjects With Somatostatin Receptor Expressing (SSTR+) Extensive Stage Small Cell Lung Cancer (ES-SCLC) [NCT05595460]Phase 131 participants (Anticipated)Interventional2022-10-10Recruiting
A Pilot Study of Neoadjuvant Cemiplimab With Platinum-Doublet Chemotherapy, and Cetuximab in Patients With Resectable, Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT04722523]Phase 130 participants (Anticipated)Interventional2021-01-20Recruiting
'ADVANCE' (A Pilot Trial) ADjuVANt Chemotherapy in the Elderly: Developing and Evaluating Lower-Toxicity Chemotherapy Options for Older Patients With Breast Cancer [NCT03858322]Phase 141 participants (Anticipated)Interventional2019-03-21Active, not recruiting
Phase II Trial of Standard Platinum Doublet Chemotherapy + Various Proton Beam Therapy (PBT) Doses in Order to Determine the Optimal Dose of PBT for Unresectable Stage 2/3 Non-Small Cell Lung Cancer [NCT03132532]Phase 218 participants (Actual)Interventional2017-07-31Active, not recruiting
A Phase III, Randomized, Open Label Trial of Nivolumab in Combination With Ipilimumab Versus Pemetrexed With Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma [NCT02899299]Phase 3605 participants (Actual)Interventional2016-11-29Completed
Immune Response in Patients With Recurrent or Metastatic Non-small Cell Lung Cancer and Performance Status of 2 Treated With a Combination of Pembrolizumab and Low Dose Weekly Carboplatin/Paclitaxel [NCT02581943]Phase 243 participants (Actual)Interventional2016-06-17Active, not recruiting
A Randomized Phase III Study Comparing One Course of Adjuvant Bleomycin, Etoposide and Cisplatin (BEP) and One Course of Carboplatin AUC7 in Clinical Stage I Seminomatous Testicular Cancer [NCT02341989]Phase 3348 participants (Anticipated)Interventional2015-04-08Recruiting
A Phase II Trial of Modified FOLFOX-6 Induction Chemotherapy Followed by Esophagectomy and Post-operative Response Based Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Adenocarcinoma of the Esophagus, Gastro-esophageal Junction, and [NCT02037048]Phase 263 participants (Anticipated)Interventional2014-02-10Active, not recruiting
Randomized Phase II Study of Docetaxel, Adriamycin, and Cytoxan (TAC) Versus Adriamycin/Cytoxan, Followed by Abraxane/Carboplatin (ACAC) +/- Trastuzumab as Neoadjuvant Therapy for Patients With Stage II-III Breast Cancer [NCT00295893]Phase 2121 participants (Actual)Interventional2005-09-27Active, not recruiting
A Phase II Trial Involving Patients With Recurrent PCNSL Treated With Carboplatin/BBBD, by Adding Rituxan (Rituximab), An Anti CD-20 Antibody, To The Treatment Regimen [NCT00074165]Phase 217 participants (Actual)Interventional2003-01-31Terminated(stopped due to Lack of accrual)
Phase Ib/II Study to Evaluate Safety and Tolerability of Neoadjuvant Nivolumab and Chemotherapy in Patients With Localized Triple-negative Breast Cancer [NCT04331067]Phase 1/Phase 215 participants (Actual)Interventional2020-11-19Active, not recruiting
Optimizing Neoadjuvant Systemic Treatment for HER2 Positive Breast Cancer - the TRAIN-2 Study [NCT01996267]Phase 3437 participants (Actual)Interventional2013-12-31Active, not recruiting
Biomarker Discovery Randomized Phase IIb Trial With Carboplatin-cyclophosphamide Versus Paclitaxel With or Without Atezolizumab as First-line Treatment in Advanced Triple Negative Breast Cancer [NCT01898117]Phase 2304 participants (Actual)Interventional2013-07-31Active, not recruiting
Randomized Phase III Trial Comparing Targretin Capsules/Carboplatin/Paclitaxel Versus Carboplatin/Paclitaxel in Chemotherapy-Naïve Patients With Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00050960]Phase 3612 participants (Actual)Interventional2002-05-31Completed
Phase II Evaluation Of Neoadjuvant Chemotherapy, Interval Debulking Followed By Intraperitoneal Chemotherapy In Women With Stage III And IV Epithelial Ovarian Cancer, Fallopian Tube Cancer Or Primary Peritoneal Cancer [NCT00008138]Phase 262 participants (Actual)Interventional2001-03-31Completed
A Phase I/II Open-Label Study of Alpelisib (BYL719) in Combination With Carboplatin in Patients With Solid Tumors and HPV+ Squamous Cell Carcinoma [NCT05472220]Phase 10 participants (Actual)Interventional2022-11-01Withdrawn(stopped due to Sponsor funding)
Phase I Study in Patients With Tumours Requiring Arginine to Assess ADI-PEG 20 With Atezolizumab, Pemetrexed and Carboplatin (ADIAtezoPemCarbo) (iTRAP Study) [NCT03498222]Phase 10 participants (Actual)Interventional2018-06-01Withdrawn(stopped due to Funder and IMP manufacturer withdrew support)
A PHASE II STUDY Of ADJUVANT CHEMOTHERAPY After SURGERY For STAGE I Lung ADENOCARCINOMA PATIENTS With MICROPAPILLARY COMPONENT More Than Or EQUAL To 20% [NCT03351842]Phase 2460 participants (Anticipated)Interventional2017-09-01Recruiting
Almonertinib Alone Versus Almonertinib Plus Chemotherapy as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive With Concomitant Non-EGFR Driver Gene Mutation Positive, Locally Advanced or Metastatic Non-Small C [NCT04500704]Phase 3166 participants (Anticipated)Interventional2020-10-31Not yet recruiting
Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus [NCT02509286]Phase 3438 participants (Actual)Interventional2016-01-31Active, not recruiting
A Phase I/II Trial of the Carboplatin/Gemcitabine Combination as First Line Treatment for Elderly Patients With Stage IV NSCLC. [NCT02175381]Phase 1/Phase 269 participants (Actual)Interventional2011-02-28Completed
A Phase I Open Label Dose Escalation Study of Oral Treatment With BIBF 1120 in Combination With Standard Treatment of Paclitaxel and Carboplatin in Patients With Advanced Gynaecological Malignancies [NCT02182245]Phase 122 participants (Actual)Interventional2005-10-31Completed
A Phase II Trial of Atezolizumab Plus CArboplatin Plus Nab-paclitaxel as First-line Therapy in Metastatic Triple-negative PD-L1 Positive Breast Cancer Patients - the GIM25-CAPT Trial [NCT05266937]Phase 2104 participants (Anticipated)Interventional2020-07-03Recruiting
A Phase II Trial of Atezolizumab Plus Chemotherapy After Progression on PD-1 or PD-L1 Inhibitor in Cisplatin-ineligible Patients With Advanced Urothelial Carcinoma: HCRN GU17-295 [NCT03737123]Phase 26 participants (Actual)Interventional2018-12-19Terminated(stopped due to Lack of accrual)
Phase II Study of Chemotherapy Followed by Peripheral Stem Cell Transplantation as First Line Therapy for Metastatic Triple-negative Breast Cancer [NCT02183805]Phase 26 participants (Actual)Interventional2014-06-17Terminated(stopped due to Difficulty accruing subjects the study accrual was closed)
A Phase I Dose-escalation and Pharmacokinetic Study of Hyperthermic Intraoperative Intraperitoneal Chemotherapy (HIPEC) Carboplatin at the Time of Cytoreductive Surgery for the Initial Treatment in Patients With Advanced Ovarian, Fallopian Tube, and Perit [NCT02199171]Phase 130 participants (Actual)Interventional2014-07-31Completed
A Randomized Prospective Clinical Trial of Paclitaxel in Combination With Carboplatin Versus Paclitaxel Plus Epirubicin as First-Line Treatment in Metastatic Breast Cancer [NCT02207361]Phase 4120 participants (Anticipated)Interventional2013-12-31Recruiting
A Pilot Study of Neoadjuvant Chemoimmunotherapy in Resectable Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT06143761]206 participants (Actual)Observational2020-12-01Completed
TQB2868 Plus Platinum-based Chemotherapy With or Without Bevacizumab in the First-line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer: a Single-arm, Open-label Phase Ⅱ Study [NCT05998941]Phase 20 participants (Actual)Interventional2023-08-31Withdrawn(stopped due to Slow progress in development, the sponsor decided to withdraw and no longer proceed.)
A Phase II Trial of GM-CSF Plus Maintenance Pembrolizumab +/- Pemetrexed After Completion of First Line Chemo-Immunotherapy in Advanced Non-Small Cell Lung Cancer Patients With PDL-1 of 1%-49% [NCT04856176]Phase 283 participants (Anticipated)Interventional2022-01-03Recruiting
Propranolol With Standard Chemoradiation for Esophageal Adenocarcinoma A Phase II Study [NCT04682158]Phase 2106 participants (Anticipated)Interventional2021-04-01Recruiting
A Phase III, Double-blind, Placebo-controlled, Multi-center International Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III Non-small Cell Lung Cancer (AEGEAN) [NCT03800134]Phase 3826 participants (Actual)Interventional2018-12-06Active, not recruiting
A Randomized Controlled Trial of Neoadjuvant Weekly Paclitaxel Versus Weekly Paclitaxel Plus Weekly Carboplatin In Women With Large Operable or Locally Advanced, Triple Negative Breast Cancer [NCT03168880]Phase 3720 participants (Actual)Interventional2010-04-30Active, not recruiting
A Pivotal Randomized, Controlled Trial of VAL-083 in Patients With Recurrent Glioblastoma Who Have Failed Standard Temozolomide/Radiation Therapy and Bevacizumab (STAR-3) [NCT03149575]Phase 32 participants (Actual)Interventional2017-10-27Terminated(stopped due to Change in clinical development plan)
Phase III Randomized Trial of Post-Radiation Chemotherapy in Patients With Newly Diagnosed Ependymoma Ages 1 to 21 Years [NCT01096368]Phase 3479 participants (Actual)Interventional2010-05-07Active, not recruiting
A Three Arm Randomized Phase II Study of Paclitaxel/Carboplatin/Bevacizumab (NSC #704865), Paclitaxel/Carboplatin/Temsirolimus (NSC #683864) and Ixabepilone (NSC #710428)/Carboplatin/Bevacizumab as Initial Therapy for Measurable Stage III or IVA, Stage IV [NCT00977574]Phase 2349 participants (Actual)Interventional2009-09-14Active, not recruiting
Randomized Phase II 2 x 2 Factorial Trial of the Addition of Carboplatin +/- Bevacizumab to Neoadjuvant Weekly Paclitaxel Followed by Dose-Dense AC in Hormone Receptor-Poor/HER2-Negative Resectable Breast Cancer [NCT00861705]Phase 2454 participants (Actual)Interventional2009-05-15Active, not recruiting
A Phase 2, Open-Label, Single-Arm Study of Single-Dose Lead-In and Neoadjuvant Trilaciclib and Chemotherapy in Patients With Early-Stage Triple Negative Breast Cancer (TNBC) [NCT05112536]Phase 224 participants (Actual)Interventional2021-11-19Completed
A Phase II Clinical Trial of Pembrolizumab in Combination With Carboplatin-paclitaxel in Patients With Advanced (Stage III B-C-IV) Ovarian, Primary Peritoneal and Fallopian Tube Cancer: MITO28/MANGO OV4 Study [NCT03410784]Phase 272 participants (Anticipated)Interventional2018-04-01Recruiting
Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer - Triple Negative Breast Cancer [NCT01815242]Phase 2336 participants (Anticipated)Interventional2013-06-30Active, not recruiting
Multicenter Phase III Randomized Study With Second Line Chemotherapy Plus or Minus Bevacizumab in Patients With Platinum Sensitive Epithelial Ovarian Cancer Recurrence After a Bevacizumab/Chemotherapy First Line [NCT01802749]Phase 3406 participants (Actual)Interventional2013-11-30Active, not recruiting
A MULTICENTER STUDY IN PATIENTS WITH STAGE III-IV EPITHELIAL OVARIAN CANCER TREATED WITH CARBOPLATIN/PACLITAXEL WITH BEVACIZUMAB: CLINICAL AND BIOLOGICAL PROGNOSTIC FACTORS [NCT01706120]Phase 4400 participants (Anticipated)Interventional2012-10-31Active, not recruiting
Weekly Versus Every 3 Week Carboplatin and Paclitaxel in Patients With Ovarian Cancer: a Phase III Randomized Multicenter Study [NCT00660842]Phase 3800 participants (Anticipated)Interventional2008-11-30Active, not recruiting
Vinorelbine, Carboplatin and Trastuzumab in Advanced Her-2 Positive Breast Cancer, a Phase 2 Study [NCT00431704]Phase 239 participants (Anticipated)Interventional2007-10-31Active, not recruiting
An Open-label, Dose Escalation Phase I Study of the Safety and Tolerability of BIBF 1120 in Combination With Carboplatin and Pegylated Liposomal Doxorubicin (PLD) in Japanese Patients With a First, Second or Third Platinum-sensitive Relapse of Advanced Ep [NCT01329549]Phase 12 participants (Actual)Interventional2011-04-30Terminated
A Multicenter, Prospective, Double-Cohort Phase II Clinical Study of Camrelizumab in Combination With Docetaxel and Platinum or Apatinib Mesylate as First-Line Treatment for Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma [NCT05156970]Phase 2178 participants (Anticipated)Interventional2021-06-24Recruiting
Phase I/II Study of Carboplatin and Etoposide in Combination With Vorinostat for Patients With Extensive Stage Small Cell Lung Cancer [NCT00702962]Phase 1/Phase 28 participants (Actual)Interventional2008-09-30Terminated(stopped due to Poor accrual)
Camrelizumab in Combination With Neoadjuvant Chemotherapy for Resectable Thoracic Esophageal Squamous Cell Carcinoma [NCT04506138]Phase 1/Phase 246 participants (Anticipated)Interventional2020-08-11Active, not recruiting
A Phase 1 Open-label Study of the Selective Inhibitor of Nuclear Export, Selinexor (KPT-330) in Combination With Paclitaxel and Carboplatin in Patients With Advanced Ovarian or Endometrial Cancers [NCT02269293]Phase 123 participants (Actual)Interventional2014-10-13Completed
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Safety and Efficacy of MEGF0444A in Combination With Carboplatin , Paclitaxel and Bevacizumab in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lun [NCT01366131]Phase 2104 participants (Actual)Interventional2011-06-30Completed
A Randomized, Open-Label, Phase 2 Trial of Paclitaxel/Carboplatin With or Without Bavituximab in Patients With Previously Untreated Locally Advanced or Metastatic Non-Squamous Non Small-Cell Lung Cancer [NCT01160601]Phase 286 participants (Actual)Interventional2010-06-30Completed
A Phase 3 Randomized, Double-blind, Placebo-controlled, Multicenter Study of AMG 386 With Paclitaxel and Carboplatin as First-line Treatment of Subjects With FIGO Stage III-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers [NCT01493505]Phase 31,015 participants (Actual)Interventional2012-01-31Terminated(stopped due to Amgen Administrative Decision - termination of LTFU)
Chemotherapy Versus Chemoradiotherapy on the Prognosis for Postoperative Endometrial Cancer With P53-mutation Profile: a Non-inferiority Randomized Controlled Trial [NCT05489848]Phase 2/Phase 3294 participants (Anticipated)Interventional2022-08-20Not yet recruiting
A Phase II Evaluation of Paclitaxel (Taxol, NSC #673089), Carboplatin (Paraplatin, NSC #241240), and BSI-201 (NSC #746045, IND #71,677) in the Treatment of Advanced, Persistent, or Recurrent Uterine Carcinosarcoma [NCT00687687]Phase 222 participants (Actual)Interventional2008-05-31Completed
A Phase II Trial of Dose Escalated Proton Beam Therapy or Photon Therapy for Resectable and Unresectable Esophageal Cancer [NCT03234842]Phase 20 participants (Actual)Interventional2017-10-30Withdrawn(stopped due to non-accrual)
A Randomized, Double-Blind, Phase II Trial of Paclitaxel + Carboplatin + Bevacizumab With or Without PRO95780 in Patients With Previously Untreated, Advanced-Stage Non-Small Cell Lung Cancer [NCT00480831]Phase 2128 participants (Actual)Interventional2007-06-30Completed
A Phase 3, Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial of AMG 706 in Combination With Paclitaxel and Carboplatin for Advanced Non-small Cell Lung Cancer. [NCT00460317]Phase 31,450 participants (Actual)Interventional2007-07-31Terminated(stopped due to Amgen discontinued the development of AMG706 because 20050201 did not meet its primary objective.)
A Randomized Phase IIb Placebo-controlled Study of R-ICE Chemotherapy With and Without SGN-40 (Anti-CD40 Humanized Monoclonal Antibody) for Second-line Treatment of Patients With Diffuse Large B-Cell Lymphoma (DLBCL) [NCT00529503]Phase 2151 participants (Actual)Interventional2007-09-30Terminated
A Phase Ib/II Study of CYT997 in Combination With Carboplatin in Relapsed Glioblastoma Multiforme [NCT00650949]Phase 1/Phase 220 participants (Actual)Interventional2009-11-30Terminated(stopped due to Strategic)
A Phase 1/2 Study of Apatinib in Combination With AP(Pemetrexed/Cisplatin) or AC(Pemetrexed/Carboplatin) as First-line Chemotherapy for Advanced Epidermal Growth Factor Receptor(EGFR) Wild Type Non-squamous Non-small Cell Lung Cancer [NCT03201146]Phase 1/Phase 248 participants (Anticipated)Interventional2017-06-27Recruiting
"Phase III Clinical Trial: Evaluation of the Combination of TRANSKRIP ® Plus Carboplatin and Paclitaxel as First Line Chemotherapy on Survival of Patients With Recurrent - Persistent Cervical Cancer" [NCT02446652]Phase 3230 participants (Anticipated)Interventional2015-07-31Not yet recruiting
A Multicenter, Open-Label, Phase Ib/II Study of AK119 and AK112 With or Without Chemotherapy in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed to Epidermal Growth Factor Receptor Tyrosine K [NCT05636267]Phase 1/Phase 2114 participants (Anticipated)Interventional2023-02-10Recruiting
Randomized Phase II Study to Compare Efficacy of CHOP Versus Fractionated ICED in Transplant-eligible Patients With Previously Untreated Peripheral T-cell Lymphoma [NCT02445404]Phase 2134 participants (Anticipated)Interventional2015-09-23Recruiting
A Phase 1/2, Open-Label, Multicenter Study to Investigate the Safety and Preliminary Efficacy of Combined Bempegaldesleukin (NKTR-214) and Pembrolizumab With or Without Chemotherapy in Patients With Locally Advanced or Metastatic Solid Tumors [NCT03138889]Phase 1/Phase 2162 participants (Actual)Interventional2017-06-09Terminated(stopped due to Sponsor decision)
A Phase Ib/II Study of Pembrolizumab With Chemotherapy in Patients With Advanced Lymphoma (PembroHeme) [NCT02408042]Phase 1/Phase 20 participants (Actual)Interventional2015-04-30Withdrawn
Phase Ib Dose-confirmation Study of ASLAN001 Combined With Weekly Paclitaxel and Carboplatin in Advanced Solid Tumours, Followed by an Open-label Phase II Study in Patients With Stage I-III HER2 Positive Breast Cancer [NCT02396108]Phase 1/Phase 255 participants (Anticipated)Interventional2015-03-31Recruiting
A Phase 2 Study of Palliative Chemo-Radiotherapy With Carbo-Taxol in Non-Curative Cancer of the Esophagus [NCT02297217]Phase 250 participants (Anticipated)Interventional2019-11-21Recruiting
Phase Ib Study of Metformin in Combination With Carboplatin/Paclitaxel Chemotherapy in Patients With Advanced Ovarian Cancer [NCT02312661]Phase 115 participants (Actual)Interventional2015-10-05Completed
A Phase II Study of Adjuvant Ado-trastuzumab Emtansine (T-DM1) in HER2-positive Salivary Gland Carcinomas [NCT04620187]Phase 255 participants (Anticipated)Interventional2020-12-24Recruiting
Phase II Trial of Preoperative Chemotherapy and Bevacizumab in Patients With Stage IB (>4 cm), II, or Select Stage III Non-Small Cell Lung Cancer [NCT00960297]Phase 24 participants (Actual)Interventional2009-08-31Terminated(stopped due to Study was terminated due to slow accrual)
A Phase II Trial of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) With Chemoradiation (Carboplatin and Taxol) as First Line Treatment for Patients With Local Regional Advanced Gastric Cancer [NCT04308837]Phase 229 participants (Anticipated)Interventional2018-12-03Recruiting
A Prospective Evaluation of Carilizumab Combined With Concurrent Chemoradiotherapy in High-risk PD-L1 Positive Stage III-IVA Cervical Cancer One-arm Phase II Clinical Study [NCT05151549]Phase 246 participants (Anticipated)Interventional2021-12-01Not yet recruiting
Neoadjuvant Icotinib With Chemotherapy for Resectable Stage II-IIIB N2 EGFR Mutation-positive Lung Adenocarcinoma: A Phase II Study [NCT05132985]Phase 245 participants (Anticipated)Interventional2022-01-01Not yet recruiting
Combination Chemotherapy With or Without Maintenance Sunitinib Malate (NSC 736511) for Untreated Extensive Stage Small Cell Lung Cancer: A Phase IB/Randomized Phase II Study [NCT00453154]Phase 1/Phase 2156 participants (Actual)Interventional2007-03-15Completed
Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC [NCT02186847]Phase 2170 participants (Actual)Interventional2014-08-31Active, not recruiting
Observational Clinical Trial of Adjuvant Chemotherapy for Non-squamous Cell Carcinoma of Non-small Cell Lung Cancer [NCT03656393]Phase 348 participants (Anticipated)Interventional2018-08-31Recruiting
A Randomized, Open-Label, Dose Escalation Study of Bevacizumab With Ambulatory Blood Pressure Monitoring in Previously Untreated Patients With Advanced Non-squamous Non-Small Cell Lung Cancer [NCT01063283]20 participants (Actual)Interventional2010-03-31Completed
Multicentre, Open-label Phase 2 Trial Evaluating the Efficacy of CARBOPLATIN in Metastatic Prostate Cancer With Gene Alterations in the Homologous Recombination Pathway [NCT03652493]Phase 216 participants (Actual)Interventional2018-09-10Terminated(stopped due to lack of efficacy)
Chemotherapy in KRAS Mutated Chemotherapy Naive Non-small Cell Lung Cancer Patients: a Phase III Study Comparing Cisplatin-pemetrexed With Carboplatin-paclitaxel-bevacizumab: NVALT 22 [NCT02743923]Phase 3203 participants (Actual)Interventional2016-04-30Active, not recruiting
Phase I Study to Evaluate the Tolerability, Safety and Efficacy of BMN-673 in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumor Malignancies That Have BRCA Mutations or Triple Negative Metastatic Breast Cancer [NCT02358200]Phase 123 participants (Actual)Interventional2015-02-23Terminated(stopped due to Funding support for the study was terminated)
To Compare the Efficacy and Safety of BP102 in Combination With Paclitaxel/Carboplatin and Avastin® in Combination With Paclitaxel/Carboplatin in First-line Treatment of Advanced or Relapsed NSCLC - a Randomized, Double-blind, Positive Parallel Control, M [NCT05169801]Phase 3520 participants (Actual)Interventional2018-01-25Completed
An Open Label, Phase 1B Safety Evaluation of Patritumab (U31287) in Combination With Cetuximab Plus Platinum Containing Therapy In Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT02350712]Phase 115 participants (Actual)Interventional2014-12-31Completed
An Extension Study to Evaluate the Safety of Veliparib as Single Agent Therapy or in Combination With Chemotherapy in Subjects With Solid Tumors [NCT02033551]Phase 147 participants (Actual)Interventional2013-12-31Completed
A Phase I Trial of Carboplatin Administered by Convection-Enhanced Delivery to Patients With Recurrent/Progressive Glioblastoma Multiforme [NCT01317212]Phase 10 participants (Actual)Interventional2015-05-31Withdrawn(stopped due to Sufficient funding could not be secured for the study)
A Phase I Study of INCB024360 (Epacadostat) Alone, INCB024360 in Combination With Pembrolizumab (MK-3475), and INCB024360 and Pembrolizumab in Combination With Chemotherapy in Patients With Advanced Solid Tumors (KEYNOTE-434) [NCT02862457]Phase 134 participants (Actual)Interventional2016-08-23Completed
Phase IB Study of Paclitaxel + Carboplatin With AVB-S6-500 in Women With Stage III or IV Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Receiving Neoadjuvant Chemotherapy [NCT03607955]Phase 10 participants (Actual)Interventional2021-06-30Withdrawn(stopped due to Trial may move forward as an NCI-sponsored trial and not an investigator initiated trial.)
Three Cycles of Adjuvant Chemotherapy for the Patients With High-risk Retinoblastoma After Enucleation: Prospective Study [NCT05080010]Phase 3500 participants (Anticipated)Interventional2020-11-01Recruiting
An Open-Label, Phase 1B Study of NEO-PV-01 With Pembrolizumab Plus Chemotherapy in Patients With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer [NCT03380871]Phase 138 participants (Actual)Interventional2018-05-04Completed
Local Consolidative Therapy (LCT) and Durvalumab (MEDI4736) for Oligoprogressive and Polyprogressive Stage III NSCLC After Chemoradiation and Anti-PD-L1 Therapy (ENDURE) [NCT04892953]Phase 251 participants (Anticipated)Interventional2021-07-07Recruiting
A Randomized, Open Label, Phase III Study of Overall Survival Comparing Pembrolizumab (MK-3475) Versus Platinum Based Chemotherapy in Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer (Keynote 042) [NCT03850444]Phase 3262 participants (Actual)Interventional2016-08-01Completed
An Exploratory Pilot Study of Nab-paclitaxel Based Induction Chemotherapy Followed by Response-Stratified Locoregional Therapy for Patients With Stage III and IV HPV-Related Oropharyngeal Cancer - the OPTIMA HPV Trial [NCT02258659]Phase 262 participants (Actual)Interventional2014-09-22Active, not recruiting
Prospective Study of Stereotactic Radiosurgery Using Diffusion-Weighted Abnormality Versus Chemotherapy for Recurrent/Progressive Glioblastoma After Second-line Chemotherapy [NCT05718466]Phase 335 participants (Actual)Interventional2010-11-30Completed
Diffusion MR (dMRT) During First Line Treatment of Non Squamous Lung Cancer With Chemotherapy Combined With Bevacizumab: Time Course and Prognostic and Predictive Impact. [NCT02195336]20 participants (Anticipated)Interventional2014-08-31Not yet recruiting
Randomized Open-label Non-inferiority Phase 3 Clinical Trial for Patients With a Stage IV Childhood Renal Tumor, Comparing Upfront Vincristine, Actinomycin-D and Doxorubicin (Standard Arm) With Upfront Vincristine, Carboplatin and Etoposide (Experimental [NCT03669783]Phase 3110 participants (Anticipated)Interventional2019-01-01Not yet recruiting
A Phase 1/2, Open-label, Multi-center Study to Evaluate theSafety and Efficacy of Selinexor Combined With Chemotherapy orTislelizumab in Relapsed or Refractory Mature T and NK Cell Lymphoma [NCT04425070]Phase 1/Phase 297 participants (Anticipated)Interventional2020-08-18Recruiting
[NCT02223884]Phase 230 participants (Actual)Interventional2011-07-31Completed
BRIDGE Trial: Phase II Trial of durvalumaB and chemotheRapy Induction Followed by Durvalumab and Radiotherapy in larGe volumE Stage III NSCLC [NCT04765709]Phase 210 participants (Actual)Interventional2021-09-24Active, not recruiting
Phase II Randomized Study: Cytoreductive Surgery (CRS) With/Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Adjuvant Chemotherapy as Initial Treatment of Ovarian, Fallopian Tube, & Primary Peritoneal Cancer [NCT02124421]Phase 232 participants (Actual)Interventional2014-04-30Active, not recruiting
A Phase 2, Multi-Center, Double-Blind, Placebo Controlled, Randomized Study of Ombrabulin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer Treated With Carboplatin/Paclitaxel [NCT01332656]Phase 2154 participants (Actual)Interventional2011-05-31Completed
[NCT00813956]Phase 280 participants (Actual)Interventional2008-12-31Completed
Phase II Study of Carboplatin and Docetaxel Followed by Epstein-Barr Virus Cytotoxic T Lymphocytes in Patients With Refractory/Relapsed EBV-positive Nasopharyngeal Carcinoma(CADEN) [NCT00953420]Phase 220 participants (Actual)Interventional2009-11-30Completed
A Phase 2 Randomized, Placebo-Controlled, Double-Blind Study of Carboplatin/Paclitaxel in Combination With ABT-869 Versus Carboplatin/Paclitaxel Alone in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) as First-Line Treatment [NCT00716534]Phase 2145 participants (Actual)Interventional2008-06-30Completed
A Phase III,Randomized, Multi-center, Open Label Study of Adjuvant Chemotherapy of Three-step Regimens (ACTS) in BRCA1/2 Wide-type Stage III and Stage IV Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (EOC, FTC, PPC) [NCT04520074]Phase 3590 participants (Anticipated)Interventional2021-10-08Recruiting
A Multi-Regional, Randomized, Double-blind, Phase 3 Study of the Efficacy and Safety of Sintilimab Plus Chemotherapy vs Placebo Plus Chemotherapy Before Surgery and Sintilimab vs Placebo After Surgery for Resectable Non-small Cell Lung Cancer [NCT05116462]Phase 3800 participants (Anticipated)Interventional2021-11-11Not yet recruiting
A Phase II Trial of Preoperative Concurrent Chemotherapy/Radiation Therapy Plus Bevacizumab/Erlotinib in the Treatment of Localized Esophageal Cancer [NCT00393068]Phase 262 participants (Actual)Interventional2007-02-28Completed
Intercalated Combination of Chemotherapy and Erlotinib in 1st Line Setting for Patients Advanced Stage Non-small-cell Lung Cancer With Low Abundant Activating EGFR Mutation(INNOVATE) [NCT02095782]Phase 210 participants (Actual)Interventional2014-03-31Terminated(stopped due to Because of the very slow enrollment, this study was stopped.)
A Randomized Open-Labeled Phase II Study of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin to Evaluate the Safety and Efficacy in Subjects With Advanced Imageable Malignancies [NCT00113438]Phase 213 participants (Actual)Interventional2005-03-31Completed
A Phase 2 Study of Docetaxel and Carboplatin for Treatment of Patients With Metastatic, Castration Resistant Prostate Cancer and Germline or Somatic DNA Repair Deficiency [NCT02985021]Phase 22 participants (Actual)Interventional2016-11-30Terminated(stopped due to Competing studies)
Peripheral Stem Cell Transplantation Protocol for Patients With Previously Treated Advanced Breast Cancer - A Phase II Pilot Study [NCT00004172]Phase 20 participants Interventional1999-10-31Completed
A Phase III Randomized, Double-blinded Trial of Platinum-based Chemotherapy With or Without Atezolizumab Followed by Niraparib Maintenance With or Without Atezolizumab in Patients With Recurrent Ovarian, Tubal or Peritoneal Cancer and Platinum Treatment-f [NCT03598270]Phase 3414 participants (Anticipated)Interventional2018-11-21Active, not recruiting
A Randomized, Open-label, Parallel Group, Multi-center Phase II Clinical Trial DCVAC/OvCa Added to Standard Chemotherapy in Women With Relapsed Platinum Sensitive Epithelial Ovarian Carcinoma [NCT02107950]Phase 271 participants (Actual)Interventional2013-11-30Completed
A Pilot Phase II Trial of Intravenous Paclitaxel and Intraperitoneal Carboplatin Followed by Radiation in Patients With Advanced Stage Uterine Serous Carcinoma [NCT02112552]Phase 24 participants (Actual)Interventional2014-04-10Terminated(stopped due to Low accrual. Study formally terminated by PI on 12/1/2017)
A Randomized Phase III Trial Comparing Two Dose-dense, Dose-intensified Approaches (ETC and PM(Cb)) for Neoadjuvant Treatment of Patients With High-risk Early Breast Cancer (GeparOcto) [NCT02125344]Phase 3961 participants (Actual)Interventional2014-12-31Completed
Phase Ib Study of Recombinant Anti-PD-L1 Monoclonal Antibody Injection (ZKAB001) Combined With Carboplatin and Etoposide in the Treatment of Extensive Small Cell Lung Cancer [NCT04346914]Phase 120 participants (Anticipated)Interventional2020-03-08Recruiting
Phase I Dose Escalation Study of a Hypofractionated Stereotactic Boost (HySBst) to the Primary Site in Patients With Stage II-III Non-small Cell Lung Cancer [NCT02252796]Phase 11 participants (Actual)Interventional2014-07-31Terminated(stopped due to Investigator left institution)
Phase II Trial of Carboplatin and Bevacizumab for the Treatment of Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial and Spinal Cord Ependymoma in Adults: A Multi-Center Trial [NCT01295944]Phase 235 participants (Actual)Interventional2011-04-27Completed
Autologous Peripheral Blood Stem Cell Transplant for Germ Cell Tumors [NCT00432094]Phase 223 participants (Actual)Interventional2006-12-19Completed
A Phase IB, Open-Label, Multi-Center Study to Determine the Efficacy and Safety of Durvalumab and/or Novel Oncology Therapies, With or Without Chemotherapy, for First-Line Stage IV Non-Small Cell Lung Cancer (NSCLC) (MAGELLAN) [NCT03819465]Phase 1175 participants (Actual)Interventional2018-12-27Active, not recruiting
A Phase 2 Multi-Cohort, Open-Label Study of Intratumoral Tavokinogene Telseplasmid Plus Electroporation in Combination With Pembrolizumab +/- Chemotherapy in Patients With Inoperable Locally Advanced/Metastatic Triple-Negative Breast Cancer [NCT03567720]Phase 265 participants (Anticipated)Interventional2018-10-11Active, not recruiting
Paclitaxel, Carboplatin And Low Dose Radiation As Induction Therapy In Locally Advanced Head And Neck Cancer [NCT00176267]Phase 226 participants (Actual)Interventional2002-09-30Completed
Neoadjuvant Therapy With Toripalimab and JS004 Combined With Platinum-based Doublet Chemotherapy for Resectable or Potentially Resectable Stage III Non-small Cell Lung Cancer: A Randomised Controlled, Open-label, Phase 2 Trial [NCT05891080]Phase 2124 participants (Anticipated)Interventional2023-07-01Not yet recruiting
An Open, Randomized Phase III Study of Famitinib With Camrelizumab Plus Treatment of Physician's Choice (TPC) Versus Camrelizumab Plus TPC in The First-line Treatment of Immunomodulatory Locally Advanced or Metastatic Triple-negative Breast Cancer [NCT05760378]Phase 3223 participants (Anticipated)Interventional2023-03-17Recruiting
Response Adapted Neoadjuvant Therapy in Gastroesophageal Cancers (RANT-GC Trial) - a Phase Ib Feasibility Trial [NCT05733689]Phase 120 participants (Anticipated)Interventional2023-12-31Not yet recruiting
Clinical Study to Evaluate the Efficacy, Safety and Tolerability of Savolitinib + Osimertinib Versus Pemetrexed + Platinum in Treatment of Patients With NSCLC With MET Amplification [NCT05015608]Phase 3250 participants (Anticipated)Interventional2021-11-22Recruiting
A Prospective Randomized Multicenter Clinical Control Study of Paclitaxel Plus Cisplatin as the First-line Chemotherapy in High Risk Gestational Trophoblastic Tumor [NCT02639650]Phase 3214 participants (Anticipated)Interventional2016-03-01Recruiting
Phase 1B Open Label Study to Assess the Safety, Pharmacokinetics and Clinical Activity of Nuc-1031 Given on Days 1 & 8 With Carboplatin on Day 1, q3-weekly for 6 Cycles in Participants With Recurrent Ovarian Cancer. [NCT02303912]Phase 125 participants (Actual)Interventional2014-11-30Completed
Phase 2 Study of Carboplatin, Etoposide, and Atezolizumab With or Without Trilaciclib in Patients With Untreated Extensive-Stage Small Cell Lung Cancer (SCLC) [NCT03041311]Phase 2107 participants (Actual)Interventional2017-06-29Terminated(stopped due to Primary Analysis and survival follow up completed per protocol. Not stopped due to safety concerns.)
A Phase Ib Study Evaluating BGJ398 in Combination With Chemotherapeutic Regimen in Patients With Stage IV, Recurrent or Persistent Carcinoma of The Cervix and Other Solid Tumors [NCT02312804]Phase 10 participants (Actual)Interventional2015-01-31Withdrawn(stopped due to Drug not available.)
Phase I/II Feasibility Study of Brentuximab Vedotin in Refractory / Relapsed Hodgkin Lymphoma Patients Who Are Treated by Chemotherapy (ICE) in Second Line and Eligible for Autologous Transplantation [NCT02686346]Phase 1/Phase 253 participants (Actual)Interventional2016-03-31Completed
A Trial Of Neoadjuvant Chemotherapy or Radiochemotherapy With Or Without SHR-1210 In Patients With Locally Advanced Resectable Esophageal Squamous Cell Carcinoma.This is a Randomised, Open, Parallel Control, Multi-center Phase II Trial. [NCT05043688]Phase 2204 participants (Anticipated)Interventional2021-09-14Not yet recruiting
Tislelizumab Combined With Albumin Paclitaxel + Carboplatin as Neoadjuvant Therapy for Patients With Stage IIIA-IIIB (N2) Lung Squamous Cell Carcinoma: A Single-arm, Single-center, Exploratory Phase II Clinical Study [NCT05024266]Phase 230 participants (Anticipated)Interventional2021-08-01Recruiting
Outcome of Cisplatin and Vinblastine Versus Paclitaxel and Carboplatin as Sequential Chemotherapy Followed by Radiotherapy in Locally Advanced Non-small Cell Lung Cancer [NCT03092986]Phase 460 participants (Actual)Interventional2017-01-01Completed
An Open-Label, First-in-Human Study of the Safety, Tolerability, and Pharmacokinetics of VX-970/M6620 in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors [NCT02157792]Phase 1200 participants (Actual)Interventional2012-12-10Completed
Multicenter Prospective Single Arm Phase II Study Evaluating Efficacy & Safety of Durvalumab With Carboplatin/Paclitaxel as First Line Treatment in Patients With Recurrent/Metastatic SCCHN Not Eligible to Standard Chemotherapy [NCT03723967]Phase 2102 participants (Anticipated)Interventional2019-05-16Recruiting
Addition of Decitabine to Carboplatin-Paclitaxel in First-Line Treatment of Advanced Ovarian Cancer: A Phase 2-3, Open-label, Randomised Controlled Trial [NCT02159820]Phase 2/Phase 3500 participants (Anticipated)Interventional2014-06-30Recruiting
The Efficacy and Safety of Tislelizumab Combined With Taxanes and Platinum as Neoadjuvant Therapy for Patients With Local Advanced Cervical Carcinoma， an Open Lable，Single-center, Exploratory Clinical Trial [NCT05013268]Phase 115 participants (Anticipated)Interventional2021-09-30Not yet recruiting
Clinical Study of Chemotherapy Combined With Camrelizumab and Apatinib in First-line Treatment of Extensive Stage Small Cell Lung Cancer [NCT05001412]Phase 136 participants (Anticipated)Interventional2021-01-27Recruiting
A Phase 2 Peri-Operative Trial of Fianlimab and Cemiplimab in Combination With Chemotherapy Versus Cemiplimab in Combination With Chemotherapy in Patients With Resectable Early Stage (Stage II to IIIB [N2]) NSCLC [NCT06161441]Phase 2180 participants (Anticipated)Interventional2024-03-05Not yet recruiting
Phase II Trial of Xevinapant and Chemoradiotherapy in Adjuvant Treatment for Patients With Head and Neck Squamous Cell Carcinoma With High Risk Pathologic Features [NCT06084845]Phase 2180 participants (Anticipated)Interventional2024-01-10Not yet recruiting
Neoadjuvant TIL- and Response-Adapted Chemoimmunotherapy for TNBC [NCT05645380]Phase 2139 participants (Anticipated)Interventional2022-12-05Recruiting
Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma [NCT05010629]Phase 235 participants (Anticipated)Interventional2021-09-14Recruiting
A Phase 1/2, Dose Escalation, Dose Expansion, and Dose Optimization Study of the Safety, Tolerability, and Anti-tumor Activity of SAR444881 Administered Alone and in Combination With Pembrolizumab, Cetuximab and/or Chemotherapy in Participants With Advanc [NCT04717375]Phase 1/Phase 2456 participants (Anticipated)Interventional2021-04-11Recruiting
A Randomized, Double Blind, Phase 3 Study of Platinum-Based Chemotherapy With or Without INCMGA00012 in First-Line Metastatic Squamous and Nonsquamous Non-Small Cell Lung Cancer (POD1UM-304) [NCT04205812]Phase 3583 participants (Actual)Interventional2020-09-27Active, not recruiting
Phase 1/2a, First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BNT411 as a Monotherapy in Patients With Solid Tumors and in Combination With Atezoliz [NCT04101357]Phase 1/Phase 255 participants (Actual)Interventional2020-06-19Active, not recruiting
An Open-Label, Randomized Phase 3 Trial of Nivolumab, or Nivolumab Plus Ipilimumab, or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Subjects With Chemotherapy-Naïve Stage IV or Recurrent Non-Small Cell Lung Cancer ( [NCT02477826]Phase 32,748 participants (Actual)Interventional2015-08-05Active, not recruiting
Neoadjuvant Phase II Trial Combining [3 FEC 100 Followed by 3 Docetaxel Associated With Trastuzumab Plus Pertuzumab] or [6 Docetaxel, Carboplatin Associated With Trastuzumab Plus Pertuzumab] According to TOP2A Status in Patients With T1c Operable, HER2-po [NCT02339532]Phase 286 participants (Actual)Interventional2015-01-31Active, not recruiting
Randomized Phase 2 Study of Conventional Dose Chemotherapy Versus High Dose Sequential Chemotherapy as First-line Therapy for Metastatic Poor Prognosis Germ Cell Tumors [NCT02161692]Phase 20 participants Interventional1996-12-31Completed
Randomized, Placebo-controlled, Double-blind Phase 2 Study of Patritumab (U3-1287) in Combination With Cetuximab Plus Platinum-based Therapy in First Line Setting in Subjects With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT02633800]Phase 287 participants (Actual)Interventional2015-12-22Terminated(stopped due to Trial was terminated by sponsor due to lack of efficacy.)
Niraparib Plus Carboplatin in Patients With Homologous Recombination Deficient Advanced Solid Tumor Malignancies [NCT03209401]Phase 123 participants (Actual)Interventional2017-10-13Active, not recruiting
A Phase I Study of Radiation Dose Intensification With Accelerated Hypofractionated Proton Therapy and Chemotherapy for Non-small Cell Lung Cancer [NCT02172846]Phase 123 participants (Actual)Interventional2014-05-22Completed
Study of Thalidomide With First-line Chemotherapy and as Maintenance Treatment of Advanced Nonsquamous NSCLC With Epidermal Growth Factor Receptor Wild-Type or Unknown Mutation Status: A Multicenter, Randomized, Prospective Clinical Trial [NCT03062800]Phase 2232 participants (Anticipated)Interventional2016-12-31Recruiting
Trabectedin/PLD Versus Continuation of Platinum-based Chemo-therapy in Patients With Disease Stabilization and no Symptom Benefit Under Platinum-based Chemotherapy for Recurrent Ovarian Cancer [NCT03690739]Phase 39 participants (Actual)Interventional2019-08-09Terminated(stopped due to Insufficient Recruitment)
Phase I/II Study of Carboplatin, Melphalan and Etoposide Phosphate in Conjunction With Osmotic Opening of the Blood-Brain Barrier and Delayed Intravenous Sodium Thiosulfate Chemoprotection, in Previously Treated Subjects With Anaplastic Oligodendroglioma [NCT00303849]Phase 1/Phase 233 participants (Actual)Interventional2005-09-15Completed
A Randomized, Open-Label Phase II Study Of ZD1839 (IRESSA™) Versus Gemcitabine And Carboplatin In Chemotherapy-Naive Patients With Advanced (Stage IIIB OR IV) Non-Small Cell Lung Cancer And ECOG Performance Status 2 [NCT00264498]Phase 238 participants (Actual)Interventional2004-10-31Completed
Comparison of Real-World Effectiveness of Pegylated Liposomal Doxorubicin Versus Paclitaxel in Platinum- Sensitive Recurrent Ovarian Cancer [NCT03562533]432 participants (Actual)Observational2018-05-17Completed
A Prospective, Single-arm, Phase II Study of Adelbelimab Combined With Carboplatin and Nab-paclitaxel in Neoadjuvant Therapy for Patients With Resectable Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT06016413]Phase 230 participants (Anticipated)Interventional2023-09-01Not yet recruiting
A Randomized Phase I/II Trial of TheraT® Vectors Expressing HPV16 Specific Antigens in Combination With Neoadjuvant Chemotherapy Followed by Transoral Robotic Surgery or Risk/Response Stratified Chemoradiotherapy for Locoregional HPV16+ Oropharyngeal Canc [NCT05108870]Phase 1/Phase 298 participants (Anticipated)Interventional2022-08-04Recruiting
A MULTICENTER, OPEN-LABEL, PHASE 1B/2 STUDY TO EVALUATE SAFETY AND EFFICACY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH CHEMOTHERAPY WITH OR WITHOUT OTHER ANTI-CANCER IMMUNOTHERAPIES AS FIRST-LINE TREATMENT IN PATIENTS WITH ADVANCED MALIGNANCIES [NCT03317496]Phase 1/Phase 267 participants (Actual)Interventional2017-12-21Terminated(stopped due to The study was terminated since there was no need for further safety or efficacy data to be collected. The participants having benefit from the investigational treatments have been moved to a continuation study (NCT05059522).)
A Phase 1 Study of Talazoparib (BMN 673) in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumors [NCT02317874]Phase 143 participants (Actual)Interventional2015-09-08Completed
A Multicenter, Open, Randomized Controlled Study of Camrelizumab+ Nab-paclitaxel + Carboplatin Versus Nab-paclitaxel + Carboplatin as Neoadjuvant Therapy for Triple Negative Breast Cancer (TNBC) [NCT04907344]Phase 2/Phase 3420 participants (Anticipated)Interventional2021-06-15Not yet recruiting
A Phase III, Randomized，Double-blind Placebo-controlled Study of Carboplatin Plus Etoposide With or Without ZKAB001 (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-stage Small Cell Lung Cancer [NCT04878016]Phase 3498 participants (Anticipated)Interventional2021-07-15Recruiting
Phase II Treatment Stratification Trial Using Neck Dissection-Driven Selection to Improve Quality of Life for Low Risk Patients With HPV+ Oropharyngeal Squamous Cell Cancer [NCT02784288]Phase 240 participants (Actual)Interventional2016-10-31Completed
ICARuS II (Intraperitoneal Chemotherapy After cytoReductive Surgery): A Multicenter, Randomized Phase II Trial of Normothermic Intraperitoneal Chemotherapy and Intravenous Chemotherapy After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemother [NCT06057935]Phase 264 participants (Anticipated)Interventional2023-09-21Recruiting
A Phase II Trial of MOnaliZumab in Combination With durvAlumab (MEDI4736) Plus Platinum-based chemotheRapy for First-line Treatment of Extensive Stage Small Cell Lung Cancer (MOZART) [NCT05903092]Phase 238 participants (Anticipated)Interventional2023-09-26Recruiting
A Phase 1a/1b Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors [NCT04956640]Phase 1400 participants (Anticipated)Interventional2021-07-19Recruiting
A Phase III Randomized, Open-Label, Multi-Center, Global Study of MEDI4736 in Combination With Tremelimumab Therapy or MEDI4736 Monotherapy Versus Standard of Care Platinum-Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic [NCT02453282]Phase 31,118 participants (Actual)Interventional2015-07-21Active, not recruiting
A Phase IIIb, Single Arm, Open-label, Multicentre Study of Durvalumab in Combination With Chemotherapy for the First Line Treatment for Patients With Advanced Biliary Tract Cancers (TOURMALINE) [NCT05771480]Phase 3140 participants (Anticipated)Interventional2023-08-16Recruiting
Phase II Study Evaluating the Effect of IMNN-001 on Second Look Laparoscopy (SLL) in Combination With Bevacizumab (BEV) and Neoadjuvant Chemotherapy (NACT) in Newly Diagnosed With Advanced Ovarian, Fallopian Tube or Primary Peritoneal Cancer [NCT05739981]Phase 1/Phase 250 participants (Anticipated)Interventional2023-02-10Recruiting
Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of Bevacizumab (Mabscale LLC, Russia) + Paclitaxel + Carboplatin to Avastin® + Paclitaxel + Carboplatin in Inoperable or Advanced Non-squamous Non-small-cell Lung Cancer [NCT05654454]Phase 3620 participants (Anticipated)Interventional2023-05-31Recruiting
A Biomarker-directed Phase 2 Platform Study in Patients With Advanced Non-Small Lung Cancer Whose Disease Has Progressed on First-Line Osimertinib Therapy. [NCT03944772]Phase 2250 participants (Anticipated)Interventional2019-06-25Active, not recruiting
Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: PRIME [NCT03878524]Phase 12 participants (Actual)Interventional2020-04-01Active, not recruiting
A Phase I/II Study Evaluating the Dosing, Safety, Efficacy, and Biological Activity of Intraperitoneal IMNN-001 (IL-12 Plasmid Formulated With PEG-PEI-Cholesterol Lipopolymer) Administered in Combination With Neoadjuvant Chemotherapy (NACT) in Patients Ne [NCT03393884]Phase 1/Phase 2130 participants (Anticipated)Interventional2018-09-05Active, not recruiting
Phase II Trial of Pemetrexed-Based Induction Chemotherapy Followed by Concomitant Chemoradiotherapy in Previously Irradiated Head and Neck Cancer Patients [NCT01172470]Phase 234 participants (Actual)Interventional2005-06-30Completed
International, Multi-Center, Open-label, Treatment Extension Study of Iniparib as Monotherapy or in Combination Chemotherapeutic Regimens in Cancer Patients Who Have Derived Clinical Benefit From Iniparib Following Completion of a Phase 1, 2 or 3 Parental [NCT01593228]Phase 337 participants (Actual)Interventional2012-05-31Completed
Neoadjuvant Study of Pyrotinib in Combination With Trastuzumab Plus Docetaxel and Carboplatin in Patients With HER2 Positive Early Stage or Locally Advanced Breast Cancer : a Single-arm,Ahead , Open-label Study [NCT03735966]Phase 275 participants (Actual)Interventional2018-11-20Completed
A Phase 1b/2 Study of Carboplatin-Paclitaxel, With or Without ISIS 183750 (an eIF4E Inhibitor), in Patients With Stage IV Non-Small Cell Lung Cancer [NCT01234038]Phase 1/Phase 2116 participants (Actual)Interventional2010-11-30Completed
Phase Ib/II Trial of the Combination of Atezolizumab With Dendritic Cell Vaccination as Maintenance Treatment in Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) After Induction Treatment [NCT04487756]Phase 1/Phase 220 participants (Anticipated)Interventional2021-03-17Recruiting
A Randomized, Molecular Driven Phase II Trial of Carboplatin-Paclitaxel-Bevacizumab vs Carboplatin-Paclitaxel-Bevacizumab-Rucaparib vs Carboplatin-Paclitaxel-Rucaparib, Selected According to HRD Status, in Patients With Advanced (Stage III B-C-IV) Ovarian [NCT03462212]Phase 1/Phase 2290 participants (Anticipated)Interventional2021-03-17Recruiting
A Study to Document Long-term Safety and Continued Benefit of Irinotecan and Carboplatin or Irinotecan in Subjects 1 - 21 Years of Age With Refractory Solid Tumors Who Have Experienced Clinical Benefit Following a Minimum of 6 Cycles of Therapy on BMS Pro [NCT00990912]Phase 1/Phase 220 participants (Actual)Interventional2004-01-31Completed
A Phase 1b/2 Study of AMG 479 in Combination With Paclitaxel and Carboplatin for the First-Line Treatment of Advanced Squamous Non-Small Cell Lung Cancer [NCT00807612]Phase 1/Phase 249 participants (Actual)Interventional2009-01-31Terminated(stopped due to Study was closed due to administrative decision)
Amgen Protocol 20060534 - A Phase 1b/2 Trial of AMG 479 or AMG 102 in Combination With Platinum-based Chemotherapy as First-Line Treatment for Extensive Stage Small Cell Lung Cancer [NCT00791154]Phase 1/Phase 2204 participants (Actual)Interventional2008-12-31Completed
A Phase 3, Multi-Center, Open-Label, Randomized Study of Gemcitabine/Carboplatin, With or Without BSI-201, in Patients With ER-, PR-, and Her2-Negative Metastatic Breast Cancer [NCT00938652]Phase 3519 participants (Actual)Interventional2009-07-31Completed
A Phase 2, Randomized, Multi-Center, Open-Label Study to Evaluate the Efficacy and Safety of Mapatumumab in Combination With Carboplatin and Paclitaxel as First Line Therapy in Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00583830]Phase 2111 participants (Actual)Interventional2007-01-31Completed
A Randomized, Controlled, Open-Label, Multicenter, Phase II Study of the Safety and Efficacy of Sunitinib in Combination With Bevacizumab, Carboplatin, and Paclitaxel in Previously Untreated Patients With Advanced Non-Small Cell Lung Cancer [NCT00434226]Phase 256 participants (Actual)Interventional2007-03-31Terminated(stopped due to Based on data collected, the combination appeared to be poorly tolearated.)
A Phase Ib, Multicenter, Open-label, Dose-escalation and Dose-expansion Study of the Safety, Tolerability and Pharmacokinetics of HB002.1T in Combination With Chemotherapy in Patients With Advanced Solid Tumors. [NCT04802980]Phase 172 participants (Anticipated)Interventional2020-04-28Recruiting
Short-course Hyperthermic IntraPEritoneal Chemotherapy (HIPEC) at Interval Debulking Surgery for High Tumor Burden Ovarian Cancer [NCT02249013]Phase 215 participants (Actual)Interventional2015-02-28Completed
Phase III Randomized Trial of Immunotherapy With or Without Consolidative Radiotherapy for Oligometastatic Head and Neck Squamous Cell Carcinoma [NCT05721755]Phase 3290 participants (Anticipated)Interventional2023-06-08Recruiting
Intra-Arterial (IA) Chemotherapy for Newly Diagnosed, Residual, or Recurrent Atypical Choroid Plexus Papilloma (ACPP) and Choroid Plexus Carcinoma (CPC) Prior to Second-Look Surgery [NCT04994977]Phase 16 participants (Anticipated)Interventional2023-05-04Recruiting
A Phase II Study of Carboplatin, Cabazitaxel and Abiraterone in High Volume Metastatic Castration Sensitive Prostate Cancer [NCT03934840]Phase 261 participants (Anticipated)Interventional2019-10-10Recruiting
A Randomized Phase III Trial of Platinum Chemotherapy Plus Paclitaxel With Bevacizumab and Atezolizumab Versus Platinum Chemotherapy Plus Paclitaxel and Bevacizumab in Metastatic (Stage IVB), Persistent, or Recurrent Carcinoma of the Cervix [NCT03556839]Phase 3404 participants (Actual)Interventional2018-09-25Active, not recruiting
A Pilot Study Evaluating the Safety of Alternating Systemic Chemotherapy and Intra-Arterial Melphalan Chemotherapy in Children With Newly Diagnosed Advanced Intra-Ocular Retinoblastoma [NCT02116959]Phase 16 participants (Actual)Interventional2014-07-23Terminated(stopped due to Low accrual)
Research on the Correlation Between Efficacy of Osimertinib and EGFR T790M Status and Ratio Via Digital Droplet PCR (ddPCR) From Peripheral Blood in NSCLC Patients [NCT05458726]Phase 280 participants (Anticipated)Interventional2020-09-15Recruiting
Olanzapine for the Prevention of Delayed Nausea and Vomiting in Patients With Gynecologic Cancers Receiving Carboplatin and Paclitaxel-based Chemotherapy and Guideline-directed Prophylactic Anti-emetics [NCT02290470]Phase 281 participants (Anticipated)Interventional2014-04-30Recruiting
Single Arm Open Label Phase II Pilot Study of Carboplatin in Patients With Metastatic Castrationresistant Prostate Cancer (CRPC) and PTEN Loss and/or DNA Repair Defects [NCT02311764]Phase 216 participants (Actual)Interventional2015-02-28Terminated
A Phase Ib Study of hPV19, a Novel Humanized Monoclonal Antibody Against Vascular Endothelial Growth Factor (VEGF),in Combination With Chemotherapy in Patients With Advanced Solid Tumors Refractory to Standard Therapy. [NCT03503604]Phase 118 participants (Anticipated)Interventional2018-05-01Not yet recruiting
Phase 1b Trial Evaluating Idelalisib in Children and Adolescents With Relapsed or Refractory Diffuse Large B-cell Lymphoma or Mediastinal B-cell Lymphoma in Combination With RICE [NCT03349346]Phase 10 participants (Actual)Interventional2019-06-30Withdrawn(stopped due to The European Medical Agency granted a Paediatric Investigational Product-specific waiver on the grounds that idelalisib is likely to be unsafe in paediatrics)
A Pilot Study of Induction Chemotherapy Followed by Surgery for Locally Advanced Resectable Head and Neck Cancer [NCT01111942]Early Phase 14 participants (Actual)Interventional2010-02-28Terminated(stopped due to lack of enrollment)
A Phase I/Ib Study of MEK162, a MEK Inhibitor, in Combination With Carboplatin and Pemetrexed in Patients With Non-squamous Carcinoma of the Lung [NCT02185690]Phase 113 participants (Actual)Interventional2018-01-11Completed
A Multi-Centered Randomized Phase II Study Comparison of Single-Agent Carboplatin vs the Combination of Carboplatin and Everolimus for the Treatment of Advanced Triple-Negative Breast Cancer [NCT02531932]Phase 262 participants (Anticipated)Interventional2015-12-16Active, not recruiting
An Open-label, Dose-finding Study to Evaluate the Safety and Pharmacokinetics (PK) of AMG 706 With Carboplatin/Paclitaxel, AMG 706 With Panitumumab and AMG 706 With Panitumumab and Carboplatin/Paclitaxel in the Treatment of Subjects With Advanced Non-Smal [NCT00094835]Phase 1/Phase 251 participants (Actual)Interventional2005-01-31Completed
A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Onartuzumab (Metmab) in Combination With Paclitaxel + Cisplatin or Carboplatin as First-Line Treatment for Patients With Stage IIIb (T4 Disea [NCT01519804]Phase 2108 participants (Actual)Interventional2012-04-30Completed
Tislelizumab Combined With Chemotherapy or Radiotherapy in the Treatment of Advanced or Recurrent Metastatic Elderly Esophageal Cancer [NCT05628610]Phase 2130 participants (Anticipated)Interventional2022-11-30Not yet recruiting
A Phase III, Randomized, Open-Label, Multi-center Study of SHR-1210(Anti-PD-1 Antibody) in Combination With Pemetrexed and Carboplatin as First Line Therapy in Subjects With Advanced/Metastatic Non-squamous Non-small Cell Lung Cancer [NCT03134872]Phase 3419 participants (Actual)Interventional2017-05-12Completed
A Pilot Study Using Carboplatin, Vincristine And Temozolomide For Children ≤ 10 Years With Progressive/Symptomatic Low-Grade Gliomas [NCT00077207]66 participants (Actual)Interventional2004-07-31Completed
Multi-center, Phase I Clinical Study to Evaluate the Safety and Tolerability of Multi-antigen Autologous Immune Cell Injection (MASCT-I) in Patients With Advanced Solid Tumor, and to Preliminarily Evaluate the Anti-tumor Efficacy of MASCT-I Alone, in Comb [NCT03034304]Phase 1193 participants (Anticipated)Interventional2017-01-31Recruiting
A Phase 1 Study of SY-1365, a Selective CDK7 Inhibitor, in Adult Patients With Advanced Solid Tumors [NCT03134638]Phase 1107 participants (Actual)Interventional2017-05-12Terminated(stopped due to Business Decision)
High-Dose Chemo-Radiotherapy for Patients With Primary Refractory and Relapsed Hodgkin's Disease [NCT00003631]Phase 2118 participants (Actual)Interventional1998-08-31Completed
Phase II Multicenter Trial of the Austrian AGO With the Combination of Liposomal Doxorubicin (Myocet®) and Carboplatin in Primary Advanced or Metastatic and Recurrent Endometrial Cancer [NCT01100359]Phase 239 participants (Anticipated)Interventional2007-11-30Recruiting
A Randomized ,Opened, Prospective Controlled Trial of Clinical Effectiveness for Icotinib as the Adjunctive Treatment After Surgery in Stage I-IIIB Lung Adenocarcinoma Patients With Epidermal Growth Factor Receptor Gene Mutation [NCT02283424]Phase 410 participants (Anticipated)Interventional2014-10-31Active, not recruiting
A Phase 2, Multi-center, Open-Label, Randomized Trial of Gemcitabine/ Carboplatin, With or Without BSI-201, in Patients With ER, PR and HER2-negative Metastatic Breast Cancer [NCT00540358]Phase 2123 participants (Actual)Interventional2007-10-31Completed
A Phase 2, Multicenter, Open Label, Randomized Trial of AMG 706 or Bevacizumab in Combination With Paclitaxel and Carboplatin for Advanced Non-squamous Non-small Cell Lung Cancer [NCT00369070]Phase 2186 participants (Actual)Interventional2007-01-31Terminated
Neoadjuvant Afatinib Combination With Chemotherapy for Stage Ⅱa-Ⅲb Non-small Cell Lung Cancer With Epidermal Growth Factor Receptor Activating Mutation [NCT04470076]Phase 230 participants (Anticipated)Interventional2020-07-10Not yet recruiting
An Open-Label Phase I/II Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer [NCT05981001]Phase 1/Phase 2170 participants (Anticipated)Interventional2023-08-01Recruiting
A Randomized, Open-Label, Multicenter Phase 3 Study to Evaluate SKB264 Monotherapy Versus Pemetrexed in Combination With Platinum in Patients With Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer With EGFR Mutation Who Have Failed to [NCT05870319]Phase 3356 participants (Anticipated)Interventional2023-06-26Recruiting
A Phase II Study of SKB264 as Monotherapy or as Combination Therapy in Subjects With Advanced or Metastatic Non-small Cell Lung Cancer [NCT05816252]Phase 2296 participants (Anticipated)Interventional2023-04-19Recruiting
Phase 3, Open-Label, Randomized, Controlled, Global Study of Telisotuzumab Vedotin (ABBV-399) Combined With Osimertinib vs Platinum-Based Chemotherapy in Subjects With c-Met Overexpressing (OE) EGFR Mutant, Locally Advanced/Metastatic Non-Squamous NSCLC A [NCT06093503]Phase 3250 participants (Anticipated)Interventional2024-05-31Not yet recruiting
Radiotherapy in Patients With Metastatic Esophageal Cancer Responding to PD-1 Inhibitor Plus Chemotherapy: a Patient Preference Multicenter Randomized Phase II Trial [NCT06084897]Phase 2120 participants (Anticipated)Interventional2023-10-16Recruiting
First-line Carboplatin/Paclitaxel/Lenvatinib/Pembrolizumab Combination for Previously Untreated Advanced or Recurrent Thymic Carcinomas [NCT05832827]Phase 235 participants (Anticipated)Interventional2023-09-04Recruiting
Serial Measurements of Molecular and Architectural Responses to Therapy (SMMART) Trial: Adaptive Clinical Treatment (ACT) [NCT05238831]Early Phase 125 participants (Anticipated)Interventional2023-12-01Not yet recruiting
Phase Ib/II Study of Induction Chemotherapy and Durvalumab (MEDI4736) and Tremelimumab With Chemoradiation for Esophageal and Gastroesophageal Junction Adenocarcinoma [NCT02962063]Phase 1/Phase 278 participants (Anticipated)Interventional2016-11-30Recruiting
DETERRED: PD-L1 blockadE To Evaluate the Safety of Lung CanceR Therapy Using Carboplatin, Paclitaxel, and Radiation CombinEd With MPDL3280A [NCT02525757]Phase 252 participants (Actual)Interventional2016-01-26Active, not recruiting
A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination With Other Agents in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL) [NCT04663347]Phase 1/Phase 2662 participants (Anticipated)Interventional2020-11-03Recruiting
Evaluate the Efficacy and Safety of HLX10, PD-1 mAb, in Combination With HLX07, EGFR mAb, in Patients With Advanced Head And Neck Tumors [NCT04297995]Phase 2131 participants (Anticipated)Interventional2020-07-29Active, not recruiting
A Randomized, Double-Blind, Multicenter, Phase III Clinical Study of HLX10 (Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection) + Chemotherapy (Carboplatin Nanoparticle Albumin Bound (Nab)-Paclitaxel) vs Chemotherapy (Carboplatin Nab-Paclitaxel [NCT04033354]Phase 3537 participants (Actual)Interventional2019-08-14Active, not recruiting
A Three Arm, Randomized, Double-Blind, Multicenter, Phase 3 Study of HLX10(Anti-PD-1 Antibody) in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04(Avastin Biosimilar) Compared With Carboplatin+Pemetrexed in 1L Stage IIIB/IIIC or IV N [NCT03952403]Phase 3643 participants (Actual)Interventional2019-12-02Active, not recruiting
A Phase 1b, Open-Label, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of MK-0482 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced/Metastatic Solid Tumors. [NCT03918278]Phase 1230 participants (Anticipated)Interventional2019-06-19Active, not recruiting
A Randomized Phase 2 Trial Of Paclitaxel, Carboplatin And Bevacizumab With Or Without PF-3512676 As First-Line Treatment Of Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer [NCT00313768]Phase 223 participants (Actual)Interventional2005-12-31Terminated(stopped due to See Termination Reason in Detailed Description.)
Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase 3 Beta (GSK 3β) Inhibitor, Plus Carboplatin in Patients With Advanced, Metastatic Salivary Gland Carcinoma [NCT04832438]Phase 20 participants (Actual)Interventional2030-12-18Withdrawn(stopped due to Replaced by NCT05010629)
A Phase I/II Study of Carboplatin and Navelbine for Advanced Non-Small Cell Lung Cancer [NCT00004096]Phase 1/Phase 20 participants Interventional1999-08-31Completed
A Phase I Study Evaluating the Safety and Pharmacokinetics of SAR240550 Administered Twice Weekly in Patients With Advanced Solid Tumors. [NCT01213381]Phase 118 participants (Actual)Interventional2010-09-30Completed
A Randomized, Phase 2 Trial With a Phase 1 Safety Run-in: Porfimer Sodium Mediated Interstitial Photodynamic Therapy and Standard of Care (SoC) Therapy Versus SoC Therapy Alone for the Treatment of Patients With Locally Advanced or Recurrent Head and Neck [NCT03727061]Phase 282 participants (Anticipated)Interventional2019-07-10Recruiting
Phase II Randomized Trial of Carboplatin/Cisplatin+Pemetrexed+PD-1 Inhibitor+/- Bevacizumab in Stage IV Non-squamous NSCLC [NCT05267366]Phase 2117 participants (Anticipated)Interventional2022-02-01Recruiting
An Open-Label Multicenter Phase Ib Study of AN0025 in Combination With Chemoradiotherapy in Patients With Locally Advanced/Locally Recurrent Esophageal Cancer [NCT05191667]Phase 132 participants (Anticipated)Interventional2022-01-18Recruiting
Mechanism of Response to IMFINZI Neoadjuvant Therapy in Non-small Cell Lung Cancer Patients Based on Multiple-omics Models [NCT04646837]Phase 1/Phase 220 participants (Anticipated)Interventional2021-05-01Recruiting
A Phase 4, Single-arm, Open-label Clinical Study of Pembrolizumab (MK-3475) to Evaluate the Efficacy and Safety of MK-3475 Plus Carboplatin and Paclitaxel as First-line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE B10). [NCT04489888]Phase 4101 participants (Actual)Interventional2020-10-27Active, not recruiting
A Phase 2 Trial of Liposomal Doxorubicin and Carboplatin in Patients With ER, PR, HER2 Negative Breast Cancer (TNBC) [NCT02315196]Phase 262 participants (Actual)Interventional2015-02-25Active, not recruiting
A Phase Ib/II Clinical Trial to Evaluate the Anti-tumor Efficacy, Safety, Tolerability, and Pharmacokinetics of IN10018 Combined With Anti-PD-1/L1 Antibody and Chemotherapy as First-line Treatment in Extensive-stage Small Cell Lung Cancer [NCT06030258]Phase 1/Phase 2120 participants (Anticipated)Interventional2023-10-30Recruiting
Intravitreal Melphalan for Intraocular Retinoblastoma [NCT05504291]Phase 228 participants (Anticipated)Interventional2022-11-04Recruiting
Niraparib vs Niraparib in Combination With Bevacizumab in Patients With Carboplatinum-taxane Based Chemotherapy in Advanced Ovarian Cancer (A Multicentre Randomised Phase III Trial) [NCT05009082]Phase 3970 participants (Anticipated)Interventional2022-09-13Recruiting
A Phase 2 Trial of Chemotherapy Followed by Response-Based Whole Ventricular &Amp; Spinal Canal Irradiation (WVSCI) for Patients With Localized Non-Germinomatous Central Nervous System Germ Cell Tumor [NCT04684368]Phase 2160 participants (Anticipated)Interventional2021-07-13Recruiting
A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Adjuvant Chemotherapy With or Without Radiotherapy for the Treatment of Newly Diagnosed High-Risk Endometrial Cancer After Surgery With Curative Intent (KEYNOTE- [NCT04634877]Phase 3990 participants (Anticipated)Interventional2021-01-10Active, not recruiting
Treatment of Newly Diagnosed Diffuse Anaplastic Wilms Tumors (DAWT) and Relapsed Favorable Histology Wilms Tumors (FHWT) [NCT04322318]Phase 2221 participants (Anticipated)Interventional2020-10-19Recruiting
A Single-Arm Phase II Study With a Safety Lead-in of Magnetic Resonance-Guided Hypofractionated Adaptive Radiation Therapy With Concurrent Chemotherapy and Consolidation Durvalumab for Inoperable Stage IIB, IIIA, and Select IIIB and IIIC Non-small Cell Lu [NCT03916419]Phase 226 participants (Actual)Interventional2019-06-20Active, not recruiting
A Biomarker-Driven Protocol for Previously Treated ALK-Positive Non-Squamous NSCLC Patients: The NCI-NRG ALK Protocol [NCT03737994]Phase 210 participants (Actual)Interventional2019-07-25Active, not recruiting
Pediatric Hepatic Malignancy International Therapeutic Trial (PHITT) [NCT03533582]Phase 2/Phase 3537 participants (Anticipated)Interventional2018-05-24Recruiting
A Phase 3 Study of Active Surveillance for Low Risk and a Randomized Trial of Carboplatin vs. Cisplatin for Standard Risk Pediatric and Adult Patients With Germ Cell Tumors [NCT03067181]Phase 32,059 participants (Anticipated)Interventional2017-05-25Recruiting
A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in Combination With Carboplatin or Cisplatin + Pemetrexed Compared With Carboplatin or Cisplatin + Pemetrexed in Patients Who Are Chemotherapy-Naive and Have Stage [NCT02657434]Phase 3578 participants (Actual)Interventional2016-04-30Completed
GOG-0262: A Phase III Trial of Every-3-Weeks Paclitaxel Versus Dose Dense Weekly Paclitaxel in Combination With Carboplatin With or Without Concurrent and Consolidation Bevacizumab (NSC #704865) in the Treatment of Primary Stage II, III or IV Epithelial O [NCT01167712]Phase 3692 participants (Actual)Interventional2010-09-27Active, not recruiting
A GCIG Intergroup Multicenter Phase III Trial of Open Label Carboplatin and Paclitaxel +/- NCI-Supplied Agent: Bevacizumab (NSC #704865) Compared With Oxaliplatin and Capecitabine +/- Bevacizumab as First Line Chemotherapy in Patients With Mucinous Epithe [NCT01081262]Phase 350 participants (Actual)Interventional2010-10-12Active, not recruiting
A Phase 1b Combination Study of INCMGA00012 Plus Chemotherapy in Participants With Advanced Solid Tumors (POD1UM-105) [NCT03920839]Phase 10 participants (Actual)Interventional2019-07-15Withdrawn(stopped due to As of November 4, 2019 the study was halted prematurely and will not resume.)
A Randomized, Double-blinded, Placebo-controlled, Multicenter Phase III Study Comparing Bevacizumab Plus Carboplatin/Paclitaxel Versus Placebo Plus Carboplatin/Paclitaxel in Patients With Advanced or Recurrent Non-Squamous Non-Small Cell Lung Cancer Who H [NCT01364012]Phase 3276 participants (Actual)Interventional2011-05-23Completed
A Phase II Study for the Treatment of Non-metastatic Nodular Desmoplastic Medulloblastoma in Children Less Than 4 Years of Age [NCT02017964]Phase 226 participants (Actual)Interventional2013-12-24Completed
A Phase 2 Open-label Single-arm Study to Evaluate the Combination of Pembrolizumab, Lenvatinib and Chemotherapy in Non-small Cell Lung Cancer (NSCLC) Harbouring Targetable Mutation and Failed Standard Tyrosine Kinase Inhibitors [NCT04989322]Phase 246 participants (Anticipated)Interventional2021-10-05Recruiting
An International Randomized Double-blind Clinical Trial of BCD-100 Plus Platinum-based Chemotherapy With and Without Bevacizumab Versus Placebo Plus Platinum-based Chemotherapy With and Without Bevacizumab as First-Line Treatment of Subjects With Advanced [NCT03912415]Phase 3316 participants (Anticipated)Interventional2019-10-01Recruiting
Improving Pre-operative Systemic Therapy for Human Epidermal Growth Factor Receptor 2 (HER2) Amplified Breast Cancer Part of a Platform of Translational Phase II Trials Based on Molecular Subtypes [NCT03894007]Phase 26 participants (Actual)Interventional2019-05-23Terminated(stopped due to Security and effect data from another ongoing study.)
Phase I Trial of Copper Chelator in Conjunction With Pegylated Liposomal Doxorubicin and Carboplatin in Patients With Platinum-resistant/-Refractory Epithelial Ovarian Cancer, Tubal Cancer and Primary Peritoneal Cancer [NCT03480750]Phase 1/Phase 218 participants (Actual)Interventional2012-09-30Completed
Study to Evaluate the Efficacy and Safety of IBI305 in Combination With Paclitaxel/Carboplatin Versus Bevacizumab in Combination With Paclitaxel/Carboplatin in Treatment-naïve Patients With Advanced or Recurrent Non-squamous NSCLC [NCT02954172]Phase 3450 participants (Actual)Interventional2016-11-28Completed
A Randomized Phase III Trial of Carboplatin, Paclitaxel and Thoracic Radiotherapy, With or Without Thalidomide, in Patients With Stage III Non-Small Cell Lung Cancer (NSCLC) [NCT00004859]Phase 3589 participants (Actual)Interventional2000-01-31Terminated(stopped due to Trial was stopped early for futility)
Neo-Adjuvant Chemotherapy and Conservative Surgery in Cervical Cancer to Preserve Fertility [NCT03852979]Phase 21 participants (Actual)Interventional2018-11-01Terminated(stopped due to study is merged with CONTESSA study)
An Open-Label, Phase I/Ib Dose Escalation Study to Assess the Safety and Tolerability of GSK1120212 in Combination With Docetaxel, Erlotinib, Pemetrexed, Pemetrexed + Carboplatin, Pemetrexed + Cisplatin, or Nab-Paclitaxel in Subjects With Advanced Solid T [NCT01192165]Phase 1169 participants (Actual)Interventional2010-09-14Completed
Phase 2 Study of Gefitinib Compared With Pemetrexed/Cisplatin in Advanced Non-Small [NCT01192243]Phase 268 participants (Anticipated)Interventional2009-12-31Recruiting
Phase I Study of the PKMYT1 Inhibitor RP-6306 in Combination With Carboplatin and Paclitaxel for the Treatment of Recurrent TP53 Ovarian and Uterine Cancer [NCT06107868]Phase 124 participants (Anticipated)Interventional2023-12-04Not yet recruiting
EFFECT-neo: A Prospective, Open-label, Multicenter Phase III Study to Evaluate Efficacy and Safety of Pembrolizumab Combined With Standard Chemotherapy in the Neoadjuvant Treatment of Local Advanced (LA) HNSCC [NCT06102395]Phase 3272 participants (Anticipated)Interventional2023-05-01Recruiting
A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB598 Monotherapy and Combination Therapy in Participants With Advanced Malignancies [NCT05891171]Phase 181 participants (Anticipated)Interventional2023-10-13Recruiting
Lurbinectedin Combined With Durvalumab in Pre-treated Patients With Extensive Stage Small-cell Lung Cancer [NCT05572476]Phase 282 participants (Anticipated)Interventional2023-10-31Recruiting
A Phase III Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib in Combination With Osimertinib Versus Platinum - Pemetrexed Based Doublet Chemotherapy in Patients With Locally Advanced or Metastatic NSCLC Harboring EGFR Activating [NCT04816214]Phase 36 participants (Actual)Interventional2021-09-22Terminated(stopped due to Novartis decided to terminate the study based on a business consideration and not related with any safety concerns. Randomized part was not initiated)
LIBRETTO-431: A Multicenter, Randomized, Open-Label, Phase 3 Trial Comparing Selpercatinib to Platinum-Based and Pemetrexed Therapy With or Without Pembrolizumab as Initial Treatment of Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer [NCT04194944]Phase 3261 participants (Actual)Interventional2020-02-17Active, not recruiting
A Multi-Center Phase II Trial of Individualized Adaptive De-escalated Radiotherapy Using Pre and Mid-Treatment FDG-PET/CT for HPV-related Oropharynx Cancer [NCT03416153]Phase 292 participants (Actual)Interventional2018-05-21Active, not recruiting
Randomized Phase II Study of Olaparib Maintenance Following Cabazitaxel-Carboplatin Induction Chemotherapy in Men With Aggressive Variant Prostate Cancer (AVPC) [NCT03263650]Phase 2119 participants (Actual)Interventional2017-10-03Active, not recruiting
A Phase 3 Study of 131I-Metaiodobenzylguanidine (131I-MIBG) or ALK Inhibitor Therapy Added to Intensive Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma (NBL) [NCT03126916]Phase 3724 participants (Anticipated)Interventional2018-05-14Active, not recruiting
A Phase 3 Placebo-Controlled Study of Carboplatin/Paclitaxel With or Without Concurrent and Continuation Maintenance Veliparib (PARP Inhibitor) in Subjects With Previously Untreated Stages III or IV High-Grade Serous Epithelial Ovarian, Fallopian Tube, or [NCT02470585]Phase 31,140 participants (Actual)Interventional2015-06-29Terminated(stopped due to Business decision not related to patient safety)
A Study of Anti-PD-1 Antibody, Sintilimab Plus Chemoradiation Before Surgery for Esophageal Cancer [NCT03940001]Early Phase 120 participants (Anticipated)Interventional2019-05-01Recruiting
Phase II Study of the Combination Carboplatin Plus Celecoxib in Heavily Pre-treated Recurrent Ovarian Cancer Patients [NCT01124435]Phase 245 participants (Actual)Interventional2003-10-31Completed
Phase II Trial of Ixabepilone and Carboplatin With or Without Bevacizumab in Patients With Previously Untreated Advanced Non-Small-Cell Lung Cancer [NCT00741988]Phase 282 participants (Actual)Interventional2008-09-30Completed
An Open-Label, Pilot Study To Investigate Feasibility and Safety Of Using Bortezomib, Rituximab, Ifosfamide, Carboplatin, Etoposide As Salvage Regime In Previously Treated Patients With Diffuse Large B-Cell Lymphoma [NCT01226849]Phase 16 participants (Actual)Interventional2010-11-30Completed
Improving Treatment Strategies in Thymic Epithelial Tumors: a TYME Collaborative Effort [NCT03921671]Phase 260 participants (Anticipated)Interventional2018-11-01Recruiting
Modulation of Autophagy With Hydroxychloroquine in Patients With Advanced/Recurrent Non-small Cell Lung Cancer - a Phase II Study. A Study of The Cancer Institute of New Jersey Oncology Group (CINJOG) [NCT01649947]Phase 232 participants (Actual)Interventional2011-12-23Completed
Efficacy and Safety of Anlotinib Combined With Platinum Plus Pemetrexed in T790M Mutation Negative Metastastic Non-squamous Non-small-cell Lung Cancer After Progression on First-line EGFR TKI: a Phase II, Muti-center, Single Arm Study [NCT03706287]Phase 1/Phase 262 participants (Anticipated)Interventional2018-12-06Recruiting
A Phase II, Open-Label, Multi-Cohort Study to Investigate the Preliminary Antitumor Activity, Safety, and Pharmacokinetics of the Anti-PD-1 Monoclonal Antibody BGB-A317 in Combination With Chemotherapy as First-Line Treatment in Chinese Subjects With Loca [NCT03432598]Phase 254 participants (Actual)Interventional2017-08-24Completed
A Pharmacokinetic/Pharmacodynamic Study With a Phase I Run-In With a PARP Inhibitor (Olaparib) in Combination With Carboplatin for Refractory or Recurrent Women's Cancers [NCT01237067]Phase 177 participants (Actual)Interventional2011-02-07Completed
Phase-3 Study, Randomized, Controlled, Multi-center, Double Blind, Comparing Palliative Radiotherapy With or Without Carboplatin [NCT03637335]Phase 326 participants (Actual)Interventional2015-08-17Terminated(stopped due to The study was stopped due to insufficient recruitment.)
A Phase 1b Open-Label, Multi-Center Study of AMG 386 in Combination With Paclitaxel and Carboplatin in Subjects With High-Risk Stage I and Stages II-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Cancers [NCT01253681]Phase 127 participants (Actual)Interventional2010-11-30Completed
Heated Intraperitoneal Chemotherapy in Primary Ovarian Cancer Patients [NCT03321188]Phase 220 participants (Anticipated)Interventional2017-12-15Recruiting
Safety and Efficacy of an Outpatient Schedule of Rituximab, Cytarabine, Carboplatin, and Dexamethasone in Relapsed/Refractory Non-Hodgkin Lymphoma. Phase I/II Trial. [NCT03892421]Phase 1/Phase 222 participants (Actual)Interventional2018-04-05Completed
International Multicenter Randomized Double-Blind Placebo-Controlled Clinical Trial Evaluating Efficacy and Safety Of BCD-100 in Combination With Pemetrexed+Cisplatin/Carboplatin Compared to Placebo in Combination With Pemetrexed+Cisplatin/Carboplatin as [NCT03912389]Phase 3292 participants (Anticipated)Interventional2019-06-01Recruiting
JS001 Combined With Nab-paclitaxel and Cisplatin or Carboplatin as First-line Treatment for Unresectable or Advanced Small Cell Esophageal Carcinoma : a Prospective, Single Arm, Single Center, Phase II Clinical Trial [NCT05173246]Phase 243 participants (Anticipated)Interventional2020-11-17Recruiting
Phase 1b, Multicenter, Open-label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02) [NCT04526691]Phase 1145 participants (Actual)Interventional2020-09-15Active, not recruiting
A Phase III, Randomized, Double-blinded, Multicenter Study of AK105 Combined With Carboplatin and Paclitaxel vs Placebo Combined With Carboplatin and Paclitaxel as First-line Therapy in Patients With Metastatic Squamous Non-small Cell Lung Cancer [NCT03866993]Phase 3338 participants (Anticipated)Interventional2018-12-20Recruiting
A Phase II Study of Pembrolizumab Plus Carboplatin in BRCA-related Metastatic Breast Cancer [NCT03732391]Phase 222 participants (Actual)Interventional2018-12-12Completed
A Prospective, Open-label Study to Evaluate Injectable Albumin-bound Paclitaxel Versus Docetaxel for the Neoadjuvant Treatment of Breast Cancer [NCT05420454]Phase 41,576 participants (Anticipated)Interventional2022-07-10Recruiting
(RICE) Plus Bortezomib (Velcade) in a Dose-Escalating Fashion for Patients With Relapsed or Primary Refractory Aggressive B-Cell NHL [NCT01300793]Phase 16 participants (Actual)Interventional2007-05-31Terminated(stopped due to closed for low accrual and no data is available.)
An Open-label Phase 2 Study of QL1706 Plus Carboplatin and Etoposide as First-line Treatment in Patients With Extensive-stage Small Cell Lung Cancer [NCT05309629]Phase 240 participants (Anticipated)Interventional2022-04-18Active, not recruiting
A Randomized, Global, Phase 3 Trial of Nivolumab Plus Epacadostat in Combination With Chemotherapy (Platinum + 5-fluorouracil) Versus the EXTREME Regimen (Cetuximab + Platinum + 5-fluorouracil) in First-line Treatment of Recurrent or Metastatic Squamous C [NCT03342352]Phase 30 participants (Actual)Interventional2017-12-15Withdrawn(stopped due to Study was cancelled prior to enrolling any patients.)
A Single Arm, Multi-center Study to Assess the Efficacy and Safety of Docetaxel Combined With Carboplatin Plus Anlotinib as First Line Treatment in Non-squamous Non-small-cell Lung Cancer (NSCLC) [NCT03799601]Phase 445 participants (Anticipated)Interventional2019-03-01Not yet recruiting
Safety Study of Bintrafusp Alfa in Combination With Other Anti-cancer Therapies in Participants With Locally Advanced or Advanced Cervical Cancer (INTR@PID 046) [NCT04551950]Phase 125 participants (Actual)Interventional2020-10-19Completed
A Phase 1 Study of Veliparib in Combination With Carboplatin And Weekly Paclitaxel in Japanese Subjects With Ovarian Cancer [NCT02483104]Phase 19 participants (Actual)Interventional2015-07-31Completed
Phase II Open-Label Study of Preoperative Weekly Paclitaxel and Carboplatin With Lapatinib (Tykerb®) in Patients With ErbB2-Positive Stage I-III Breast Cancer [NCT01309607]Phase 234 participants (Anticipated)Interventional2011-04-30Active, not recruiting
A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Bemarituzumab Monotherapy and Combination With Other Anti-Cancer Therapy in Subjects With Squamous-Cell Non-Small-Cell Lung Cancer (FORTITUDE-201) [NCT05267470]Phase 1180 participants (Anticipated)Interventional2022-03-29Active, not recruiting
Phase 1/2 Study of Pemetrexed (Alimta) Plus Carboplatin, or Pemetrexed Plus Cisplatin With Concurrent Radiation Therapy Followed by Every-21-Day Pemetrexed Consolidation in Patients With Favorable-Prognosis Inoperable Stage IIIA/B Non-Small-Cell Lung Canc [NCT00482014]Phase 1/Phase 2120 participants (Actual)Interventional2007-05-31Completed
A Phase 1 Study of SGN-B6A in Advanced Solid Tumors [NCT04389632]Phase 11,006 participants (Anticipated)Interventional2020-06-08Recruiting
Tandem Myeloablative Consolidation Therapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma [NCT02605421]Phase 212 participants (Anticipated)Interventional2016-06-30Recruiting
A Multicentre Phase II Study of Adavosertib Plus Chemotherapy in Patients With Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer [NCT02272790]Phase 295 participants (Actual)Interventional2015-01-30Completed
Safety and Dose Finding Study of Oral MP470, a Multi-targeted Tyrosine Kinase Inhibitor, in Combination With Standard-of-Care Chemotherapy Regimens [NCT00881166]Phase 1101 participants (Actual)Interventional2007-11-30Completed
Safety and Efficacy Pilot Trial of the Anti-Viral and Anti-Tumor Activity of Velcade Combined With (R)ICE in Subjects With EBV and/or HHV-8 Positive Relapsed/Refractory AIDS-Associated Non-Hodgkin's Lymphoma [NCT00598169]Phase 123 participants (Actual)Interventional2007-11-30Completed
Phase Ⅱ Study of Induction Erlotinib Therapy in Stage III A(N2) Non-small Cell Lung Cancer Proceeding to Mediastinoscopy/PET and Thoracotomy/Radiotherapy [NCT00600587]Phase 224 participants (Actual)Interventional2007-09-30Completed
Liposomal iRInotecan, Carboplatin or oXaliplatin in the First Line Treatment of Esophagogastric Cancer: a Randomized Phase 2 Study [NCT03764553]Phase 2310 participants (Anticipated)Interventional2019-05-01Recruiting
A Phase I/IIB Study of Combination Weekly Carboplatin, Cetuximab and Dose Escalation of RAD001 in Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT01283334]Phase 1/Phase 220 participants (Actual)Interventional2011-01-31Completed
A Phase II Study of Neoadjuvant Toripalimab Plus Platinum-based Doublet for Potentially Resectable Stage III Non-small Cell Lung Cancer [NCT04304248]Phase 230 participants (Anticipated)Interventional2019-08-01Active, not recruiting
A Phase II, Randomized, Multicenter, Double-Blind, Controlled Study of Tobemstomig Plus Platinum-Based Chemotherapy Versus Pembrolizumab Plus Platinum-Based Chemotherapy in Patients With Previously Untreated Locally Advanced or Metastatic Non-Small Cell L [NCT05775289]Phase 2180 participants (Anticipated)Interventional2023-03-15Recruiting
A Multicenter Phase II Randomized Trial Of Immunotherapy Versus Chemotherapy Guided By Circulating Tumor DNA-Based Molecular Response On Patients With Metastatic NSCLC [NCT05715229]Phase 2108 participants (Anticipated)Interventional2023-09-29Recruiting
NASSIST (Neoadjuvant Chemoradiation +/- Immunotherapy Before Surgery for Superior Sulcus Tumors): A Randomized Phase II Trial of Trimodality +/- Atezolizumab in Resectable Superior Sulcus Non-Small Cell Lung Cancer [NCT04989283]Phase 20 participants (Actual)Interventional2021-09-09Withdrawn(stopped due to Due to no accrual)
A Phase 2 Study of M6620 (VX-970, Berzosertib) in Combination With Carboplatin Compared With Docetaxel in Combination With Carboplatin in Metastatic Castration-Resistant Prostate Cancer [NCT03517969]Phase 2130 participants (Anticipated)Interventional2019-05-29Active, not recruiting
A Pilot Study of Nivolumab With or Without Ipilimumab in Combination With Front-Line Neoadjuvant Dose Dense Paclitaxel and Carboplatin Chemotherapy and Post-Surgical Dose Dense Paclitaxel and Carboplatin Chemotherapy in Patients With High Grade Serous Ova [NCT03245892]Phase 140 participants (Anticipated)Interventional2017-08-04Active, not recruiting
A Phase 2 Feasibility Study of Abraxane and Carboplatin in Epithelial Neoplasms of the Uterus [NCT02744898]Phase 223 participants (Actual)Interventional2016-07-31Completed
A Phase II Study of Prophylactic Radiation Therapy for the Prevention of Hemoptysis in Advanced Non Small Cell Lung Cancer in Combination With Bevacizumab, Paclitaxel, and Carboplatin in Patients at High Risk for Bevacizumab-Associated Hemoptysis [NCT00387374]Phase 272 participants (Actual)Interventional2006-10-31Completed
TGF-β And PDL-1 Inhibition in Esophageal Squamous Cell Carcinoma Combined With Chemoradiation TheRapY [NCT04481256]49 participants (Anticipated)Interventional2020-11-11Recruiting
A Phase II Study of Docetaxel/Cisplatin/5-Fluorouracil (TPF) Induction Chemotherapy Followed by Concurrent Chemoradiotherapy Using a Modified Radiation Dose in Patients With Newly Diagnosed HPV Positive, Locally Advanced Squamous Cell Carcinoma of the Oro [NCT01221753]Phase 27 participants (Actual)Interventional2011-07-31Terminated(stopped due to Due to slow accrual)
DAREON™-7: A Phase I, Open-label, Dose Escalation and Expansion Trial to Investigate Safety and Tolerability of BI 764532 Intravenous Infusions in Combination With Standard of Care (Platinum and Etoposide) in First-line Treatment of Patients With Neuroend [NCT06132113]Phase 155 participants (Anticipated)Interventional2023-12-20Recruiting
Phase 1b Study of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC) [NCT01199055]Phase 116 participants (Actual)Interventional2010-03-31Completed
CPT-SIOP-2009: Intercontinental Multidisciplinary Registry and Treatment Optimization Study for Patients With Choroid Plexus Tumors [NCT01014767]Phase 327 participants (Actual)Interventional2009-11-30Terminated(stopped due to PI departure from coordinating institution)
A Multicenter, Randomized, Open-label, Phase III Trail of Adjuvant Chemoradiotherapy Versus Adjuvant Radiotherapy in Patients Undergoing Radical Esophagectomy for Pathologic Lymph Node Positive Esophageal Squamous Cell Carcinoma [NCT02570893]Phase 3366 participants (Anticipated)Interventional2015-05-31Recruiting
A Randomised Phase II Study Of Nintedanib (BIBF1120) Compared To Chemotherapy in Patients With Recurrent Clear Cell Carcinoma Of The Ovary Or Endometrium [NCT02866370]Phase 2120 participants (Anticipated)Interventional2015-04-30Recruiting
Randomized, Open-Label, Phase 3 Study of Pemetrexed Plus Carboplatin and Bevacizumab Followed by Maintenance Pemetrexed and Bevacizumab Versus Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Stage IIIB or I [NCT00762034]Phase 3939 participants (Actual)Interventional2008-12-31Completed
Investigating Denosumab as an add-on Neoadjuvant Treatment for RANK-positive or RANK-negative Primary Breast Cancer and Two Different Nab-Paclitaxel Schedules ; 2x2 Factorial Design (GeparX) [NCT02682693]Phase 2780 participants (Actual)Interventional2017-02-13Completed
Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies [NCT00646659]Phase 247 participants (Actual)Interventional2008-02-29Terminated(stopped due to Recruitment was suspended prematurely for safety concerns and closed after IDMC review)
Advanced Metastatic Non-small Cell Lung Cancer Patients Aged or PS Score 2 Points for First Line Application Pemetrexed/Carboplatin Chemotherapy Regimens Sequential Pemetrexed Single Drug Maintenance Treatment of Clinical Research and Related Predictive B [NCT01860508]94 participants (Anticipated)Interventional2013-02-28Recruiting
Pilot Trial of Intraperitoneal Paclitaxel and Carboplatin With IV Avastin Therapy in Treatment of Women With Newly Diagnosed, Optimally Cytoreduced Carcinoma of Mullerian Origin [NCT00652119]Phase 146 participants (Actual)Interventional2008-02-29Active, not recruiting
Phase Ib/II Trial of Pembrolizumab (MK-3475) Combination Therapies in Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-365) [NCT02861573]Phase 1/Phase 21,200 participants (Anticipated)Interventional2016-11-17Recruiting
A Phase 3 Randomized, Open-Label Clinical Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Epacadostat, Pembrolizumab Monotherapy, and the EXTREME Regimen as First Line Treatment for Recurrent or Metastatic Head and Neck Squamous Cell Carci [NCT03358472]Phase 389 participants (Actual)Interventional2017-12-01Active, not recruiting
A Phase I Open Label Study of GSK3359609 Administered Alone and in Combination With Anticancer Agents in Subjects With Selected Advanced Solid Tumors [NCT02723955]Phase 1829 participants (Actual)Interventional2016-06-23Completed
A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma [NCT02358031]Phase 3882 participants (Actual)Interventional2015-03-19Completed
Phase 2 Single Arm Trial of Cisplatin, Nab-Paclitaxel, and Cetuximab (CACTUX) in Patients With Incurable Head and Neck Squamous Cell Carcinoma (HNSCC) [NCT02270814]Phase 274 participants (Actual)Interventional2015-02-02Active, not recruiting
Stereotactic Body Radiation Therapy for Inoperable Locally-advanced Non-small Cell Lung Cancer [NCT01899989]Phase 139 participants (Actual)Interventional2013-07-05Active, not recruiting
Phase I/II Trial Of Repeated Super-selective Intraarterial Cerebral Infusion Of Bevacizumab Plus Carboplatin For Treatment Of Relapsed/Refractory Glioblastoma Multiforme And Anaplastic Astrocytoma [NCT01386710]Phase 1/Phase 254 participants (Anticipated)Interventional2011-09-30Suspended(stopped due to PI left previous institution study will reopen at new institution.)
A Phase 2 Clinical Trial of Pembrolizumab in Combination With Carboplatin and Cabazitaxel in Aggressive Variant Metastatic Castration Resistant Prostate Cancer [NCT05563558]Phase 242 participants (Anticipated)Interventional2023-05-05Recruiting
PET-Adjusted IMRT for NSCLC Trial (PAINT) [NCT02073968]Phase 235 participants (Actual)Interventional2013-07-31Completed
A Phase II Study of Postoperative Intensity Modulated Radiation Therapy (IMRT) With Concurrent Cisplatin and Bevacizumab Followed by Carboplatin and Paclitaxel for Patients With Endometrial Cancer [NCT01005329]Phase 234 participants (Actual)Interventional2009-11-06Completed
A Dose-Escalation Study to Evaluate the Safety and Tolerability of SCH 717454 in Combination With Different Treatment Regimens in Subjects With Advanced Solid Tumors (Phase 1B/2; Protocol No. P04722) [NCT00954512]Phase 1/Phase 215 participants (Actual)Interventional2009-09-25Terminated(stopped due to This study was terminated for business reasons.)
Phase 3 Study of Pemetrexed, Cisplatin, and Radiotherapy Followed by Consolidation Pemetrexed Versus Etoposide, Cisplatin, and Radiotherapy Followed by Consolidation Cytotoxic Chemotherapy of Choice in Patients With Unresectable, Locally Advanced, Stage I [NCT00686959]Phase 3598 participants (Actual)Interventional2008-09-30Completed
Phase I Dose Escalating Study Of Tas-106 In Combination With Carboplatin In Patients With Solid Tumors [NCT00752011]Phase 145 participants (Actual)Interventional2008-06-30Completed
A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of XL147 (SAR245408) in Combination With Paclitaxel and Carboplatin in Subjects With Solid Tumors [NCT00756847]Phase 152 participants (Actual)Interventional2008-09-30Completed
Phase II Clinical Trial of Intravenous Paclitaxel and Carboplatin Plus Intraperitoneal Paclitaxel as an Adjuvant Chemotherapy in Patients With Optimally Debulked Advanced Epithelial Ovarian Carcinoma [NCT00919984]Phase 222 participants (Actual)Interventional2007-05-31Terminated(stopped due to This study stopped due to slow accrual.)
Trastuzumab in a Neo-adjuvant Regimen for HER2+ Breast Cancer - the TRAIN Study [NCT00768859]Phase 2111 participants (Actual)Interventional2008-09-30Completed
Neoadjuvant Weekly Nab-paclitaxel (Abraxane®) Plus Carboplatin Followed By Doxorubicin Plus Cyclophosphamide With Bevacizumab Added Concurrently To Chemotherapy For Palpable And Operable Triple Negative Invasive Breast Cancer [NCT00777673]Phase 260 participants (Anticipated)Interventional2008-10-31Active, not recruiting
Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma [NCT00499616]Phase 3464 participants (Actual)Interventional2007-10-08Completed
PhII Study of Concurrent Chemoradiotherapy With Weekly Docetaxel, Carboplatin and Radiation Therapy Followed by Consolidation Chemotherapy With Docetaxel and Carboplatin for Locally Advanced Inoperable Non-small Cell Lung Cancer (NSCLC) [NCT00664105]Phase 263 participants (Actual)Interventional2004-02-29Terminated(stopped due to Treatment became standard.)
Randomized Phase II Study of Pemetrexed Versus Pemetrexed and Carboplatin as Second Line Chemotherapy in Advanced Non-small-cell Lung Cancer (NSCLC). [NCT00786331]Phase 2230 participants (Anticipated)Interventional2007-07-31Recruiting
Study Comparing Paclitaxel Plus Carboplatin Versus Anthracyclines Followed by Docetaxel as Adjuvant Chemotherapy for Triple Negative Breast Cancer [NCT04031703]Phase 3647 participants (Actual)Interventional2011-01-01Completed
A Phase II, Double-blind, Placebo-controlled, Multi-centre, Randomised Study of ZD4054 (Zibotentan) Plus Carboplatin and Paclitaxel or Placebo Plus Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer Sensitive to Platinum-based Chemotherap [NCT00929162]Phase 2120 participants (Actual)Interventional2009-06-30Terminated(stopped due to Primary objective of the trial was not met and so there was no benefit in collecting further information)
Randomized Trial of Concomitant Chemotherapy in Patients With Locally Advanced HNSCC Treated by Radiotherapy-erbitux [NCT00609284]Phase 3406 participants (Actual)Interventional2008-02-15Completed
A Phase I Multiple Ascending Dose Study of BMS-754807 in Combination With Paclitaxel and Carboplatin in Subjects With Advanced or Metastatic Solid Tumors [NCT00793897]Phase 121 participants (Actual)Interventional2009-04-30Completed
A Phase II Study of Docetaxel - Carboplatin as Second Line Treatment in Patients With Refractory or Relapsed Small Cell Lung Cancer [NCT00686985]Phase 255 participants (Anticipated)Interventional2007-09-30Recruiting
A Multicenter, Randomized, Phase II Study of Pemetrexed and Carboplatin With or Without Anlotinib Hydrochloride for Advanced or Locally-advanced Osimertinib-resistant Non-squamous Non-small Cell Lung Cancer (ALTER-L031) [NCT04136535]Phase 2105 participants (Anticipated)Interventional2019-10-18Not yet recruiting
A Randomized, Double-blind, Placebo-controlled, Multi-center Phase 3 Study Evaluating Efficacy, Safety and Pharmacokinetics of Trilaciclib In Extensive-Stage Small Cell Lung Cancer Patients Receiving Carboplatin Combined With Etoposide or Topotecan [NCT04902885]Phase 395 participants (Actual)Interventional2021-05-25Completed
A Phase 2, Randomized, Open Label Study Of Figitumumab (CP-751,871) Plus Cisplatin (Or Carboplatin) And Etoposide, Versus Cisplatin (Or Carboplatin) And Etoposide Alone, As First Line Treatment In Patients With Extensive Stage Disease Small Cell Lung Canc [NCT00977561]Phase 29 participants (Actual)Interventional2010-04-30Terminated(stopped due to See termination reason in detailed description.)
Phase I/II Study of Carboplatin in Association With Weekly Oral Topotecan in Patients With Metastatic or Recurrent Cervical Cancer [NCT00807079]Phase 1/Phase 212 participants (Actual)Interventional2008-09-30Completed
A Phase II Study of Combination Therapy of Carboplatin -Gemcitabine Plus Bevacizumab Beyond Progression in Patients With Locally Advanced and/or Metastatic Non-small Cell Lung Cancer (NSCLC) Who Have Not Received Prior Systemic Therapy [NCT00702975]Phase 235 participants (Actual)Interventional2008-09-30Completed
Phase Ib Study To Evaluate The Safety Of Combining IGF-1R Antagonist R1507 With Multiple Standard Chemotherapy Drug Treatments In Patients With Advanced Malignancies [NCT00811993]Phase 1104 participants (Actual)Interventional2009-02-28Terminated
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Etoposide With or Without Tislelizumab (BGB-A317) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer [NCT04005716]Phase 3457 participants (Actual)Interventional2019-07-22Active, not recruiting
Randomized Phase II Study of Weekly Irinotecan/Carboplatin (ICb) With or Without Cetuximab (Erbitux) in Patients With Metastatic Breast Cancer [NCT00248287]Phase 2154 participants (Actual)Interventional2005-07-28Active, not recruiting
Phase II Study of Doxil and Carboplatin, Plus Herceptin in HER2+ Patients, in Metastatic Breast Cancer [NCT00303108]Phase 2136 participants (Actual)Interventional2005-12-31Completed
Phase II Study on Carboplatin-Paclitaxel-Pembrolizumab in Neoadjuvant Treatment of Locally Advanced Cervical Cancer [NCT04238988]Phase 245 participants (Anticipated)Interventional2021-02-18Recruiting
Recombinant Human Endostatin Durative Transfusion Combined With Pemetrexed Plus Cisplatin or Carboplatin in the First-line Treatment of Advanced Lung Adenocarcinoma With Wild-type EGFR or ALK-negative [NCT02804646]Phase 4100 participants (Anticipated)Interventional2016-06-30Recruiting
A Phase I/II Study Evaluating the Safety, Tolerability, and Efficacy of GLS-012 and GLS-010 in Patients With Advanced Non-Small Cell Lung Cancer (Triumph-02) [NCT05978401]Phase 1/Phase 2152 participants (Anticipated)Interventional2023-08-10Not yet recruiting
Reduced-dose Radiotherapy Following High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With Central Nervous System Non-germinomatous Germ Cell Tumors [NCT02784054]Phase 225 participants (Anticipated)Interventional2014-04-30Recruiting
AN INTERNATIONAL PROSPECTIVE TRIAL ON MEDULLOBLASTOMA (MB) IN CHILDREN OLDER THAN 3 TO 5 YEARS WITH WNT BIOLOGICAL PROFILE (PNET 5 MB - LR and PNET 5 MB - WNT-HR), AVERAGE-RISK BIOLOGICAL PROFILE (PNET 5 MB -SR), OR TP53 MUTATION, AND REGISTRY FOR MB OCCU [NCT02066220]Phase 2/Phase 3360 participants (Anticipated)Interventional2014-06-30Active, not recruiting
A Multicenter, Randomized Trial of Stereotactic Radiotherapy Combined With Adebrelimab and TCb (Nab-paclitaxel + Carboplatin) Versus Adebrelimab Combined With TCb (Nab-paclitaxel + Carboplatin) in Neoadjuvant Treatment of Triple-negative Breast Cancer [NCT06165900]Phase 2136 participants (Anticipated)Interventional2023-12-15Not yet recruiting
A Feasibility Study to Evaluate the Addition of Tumor Treating Fields to Treatment of Locally Advanced Stage III NSCLC [NCT06124118]Phase 130 participants (Anticipated)Interventional2023-11-03Suspended(stopped due to Will re-open to accrual pending IRB amendment)
DAREONᵀᴹ-8: A Phase I, Open-label, Dose Escalation and Expansion Trial of Repeated Intravenous Infusions of BI 764532 Combined With Standard of Care (Platinium, Etoposide, and Anti-PD-L1) in Patients With Extensive-stage Small Cell Lung Carcinoma [NCT06077500]Phase 160 participants (Anticipated)Interventional2024-01-25Not yet recruiting
An Open-label, Randomized, Controlled Phase 3 Study of Disitamab Vedotin in Combination With Pembrolizumab Versus Chemotherapy in Subjects With Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma That Expresses HER2 (IHC 1+ and Greate [NCT05911295]Phase 3700 participants (Anticipated)Interventional2023-09-22Recruiting
A Phase III, Randomised, Open-Label Study of Savolitinib in Combination With Osimertinib Versus Platinum-Based Doublet Chemotherapy in Participants With EGFR Mutated, MET-Overexpressed and/or Amplified, Locally Advanced or Metastatic Non-Small Cell Lung C [NCT05261399]Phase 3324 participants (Anticipated)Interventional2022-08-03Recruiting
A Phase III, Randomized, Open-Label, Multicenter Study of Lurbinectedin in Combination With Atezolizumab Compared With Atezolizumab as Maintenance Therapy in Participants With Extensive-Stage Small-Cell Lung Cancer (ES-SCLC) Following First-Line Induction [NCT05091567]Phase 3690 participants (Anticipated)Interventional2021-11-18Recruiting
Pilot Study of Serial Plasma Genotyping to Guide the Adaptive Treatment of Advanced NSCLC Receiving First-line Pembrolizumab [NCT04166487]Phase 240 participants (Actual)Interventional2020-01-13Active, not recruiting
Open Label Phase 2 Study of Tisotumab Vedotin for Locally Advanced or Metastatic Disease in Solid Tumors [NCT03485209]Phase 2692 participants (Anticipated)Interventional2018-06-25Recruiting
A Multicenter, Randomized, Double-Blind Trial in Subjects With Non-Squamous Non-Small Cell Lung Cancer (TASUKI-52) [NCT03117049]Phase 3550 participants (Actual)Interventional2017-06-13Completed
A Single-arm, Phase II Study of Neoadjuvant MPDL3280A, Nab-paclitaxel and Carboplatin (MAC) in Resectable Non-small Cell Lung Cancer (NSCLC) [NCT02716038]Phase 239 participants (Actual)Interventional2016-06-07Completed
An Exploratory Study on the Safety, Tolerability, Pharmacokinetics and Efficacy of HLX07 (Recombinant Anti-EGFR Humanized Monoclonal Antibody) Combined With Chemotherapy in Patients With Advanced Solid Tumors. [NCT03577704]Phase 1/Phase 256 participants (Actual)Interventional2018-08-08Completed
A Phase Ib Study of Selumetinib in Patients With Previously Treated or Untreated Advanced/Metastatic NSCLC Who Are Receiving Standard Chemotherapy Regimens. [NCT01783197]Phase 139 participants (Actual)Interventional2013-06-04Completed
A Phase II/III Double Blind Randomized Trial of AZD2171 Versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00245154]Phase 2/Phase 3296 participants (Actual)Interventional2005-11-03Completed
A Phase II Study of Cisplatin and Gemcitabine in Patients With Locally Advanced/Recurrent or Metastatic Malignant Salivary Gland Tumors [NCT00079079]Phase 234 participants (Actual)Interventional2003-10-27Completed
Phase I/II Clinical Trial of the Combination of Carboplatin, Eribulin Mesylate, and E7449 in Patients With BRCA-Related Cancers [NCT02396433]Phase 1/Phase 20 participants (Actual)Interventional2015-04-30Withdrawn(stopped due to lack of funding.)
A Phase 3, Controlled, Open-label, Randomized Study of RRx-001 Administered Sequentially With a Platinum Doublet or a Platinum Doublet in Third-Line or Beyond Small Cell Lung Cancer [NCT03699956]Phase 318 participants (Actual)Interventional2018-12-24Terminated(stopped due to RRx-001 will be studied under a new global, phase 3 clinical trial)
Randomized, Double-Blind, Phase 2/3 Study in Subjects With Malignant Pleural Mesotheliomato Assess ADI-PEG 20 With Pemetrexed and Cisplatin (ATOMIC-Meso Phase 2/3 Study) [NCT02709512]Phase 2/Phase 3249 participants (Actual)Interventional2017-08-01Completed
A Phase 1b/2 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Mirvetuximab Soravtansine (IMGN853) in Combination With Bevacizumab, Carboplatin, Pegylated Liposomal Doxorubicin, Pembrolizumab, or Bevacizumab + Carboplatin, in Adults With [NCT02606305]Phase 1/Phase 2264 participants (Actual)Interventional2015-12-31Completed
Neoadjuvant and Adjuvant Olaparib Plus Pembrolizumab Following Platinum Based Chemotherapy Plus Pembrolizumab for Germline BRCA Mutated Triple Negative Breast Cancer (WJOG14020B) [NCT05485766]Phase 223 participants (Anticipated)Interventional2022-10-01Not yet recruiting
To Evaluate the Efficacy and Safety of Toripalimab Combined With Chemotherapy (Epirubicin + Cyclophosphamide → Nab-paclitaxel + Carboplatin) in the Neoadjuvant Treatment of Triple-negative Breast Cancer After High-intensity Focused Ultrasound (HIFU) Induc [NCT05491694]Phase 220 participants (Anticipated)Interventional2022-09-01Not yet recruiting
EGFR-TKI With Chemotherapy as First Line Treatment in Stage IIIB/IV NSCLC Patients With Both EGFR Mutation and BIM Deletion Polymorphism [NCT02859077]Phase 3100 participants (Anticipated)Interventional2016-08-31Not yet recruiting
Randomized Phase II Study of IMMU-132 Alone or in Combination With Carboplatin in Patients With Relapsed/Refractory Triple-Negative Breast Cancer [NCT02161679]Phase 20 participants (Actual)Interventional2016-08-31Withdrawn(stopped due to FDA asked to administratively split from IND115621- to open a new IND you need to file a protocol we only drafted it to get the IND open - never initiated)
A Phase 2 Randomized, Multicenter, Double-Blind Study of the Glutaminase Inhibitor Telaglenastat With Pembrolizumab and Chemotherapy Versus Placebo With Pembrolizumab and Chemotherapy in First-Line, Metastatic KEAP1/NRF2-Mutated, Nonsquamous, Non-Small Ce [NCT04265534]Phase 240 participants (Actual)Interventional2020-07-24Terminated(stopped due to Lack of Clinical Benefit)
A Phase I Followed by a Randomized, Phase II Study of Carboplatin and Etoposide With or Without Obatoclax Administered Every 3 Weeks to Patients With Extensive- Stage Small Cell Lung Cancer (ES-SCLC) [NCT00682981]Phase 1/Phase 2218 participants (Actual)Interventional2008-05-31Completed
Leukemia SPORE Phase II Randomized Study of Decitabine Versus Decitabine and Carboplatin Versus Decitabine and Arsenic in Relapsed, Refractory, and Elderly Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) [NCT02190695]Phase 292 participants (Actual)Interventional2013-04-01Completed
A Phase I-II Study of Induction Chemotherapy With Carboplatin and Gemcitabine, Followed by Chemoradiotherapy With Paclitaxel and Vinorelbine for Patients With Locally Advanced Non-Small Cell Lung Cancer [NCT00004093]Phase 1/Phase 236 participants (Actual)Interventional1999-08-31Terminated(stopped due to Original Principal Investigator left the institution.)
Surgery or Radiotherapy After PD-L1 Inhibitor (TQB-2450) and Chemotherapy Induction Therapy in Patients With Limited-stage Small-cell Lung Cancer [NCT04539977]Phase 240 participants (Anticipated)Interventional2020-09-01Recruiting
A Phase Ib Trial of Vaginal Cuff Brachytherapy + Pembrolizumab (MK3475) Followed by 3 Cycles of Dose Dense Paclitaxel/q 21 Day Carboplatin + Pembrolizumab (MK3475) in High Intermediate Risk Endometrial Cancer [NCT03932409]Phase 140 participants (Anticipated)Interventional2020-02-19Recruiting
Phase 1b/2 Clinical Trial of Neoadjuvant Pembrolizumab Plus Concurrent Chemoradiotherapy With Weekly Carboplatin and Paclitaxel in Adult Patients With Resectable, Locally Advanced Adenocarcinoma of the Gastroesophageal Junction or Gastric Cardia [NCT02730546]Phase 1/Phase 231 participants (Actual)Interventional2016-06-24Active, not recruiting
Hyperthermic Intraperitoneal Chemotherapy for Recurrent Ovarian Cancer [NCT02672098]Phase 120 participants (Anticipated)Interventional2016-07-14Recruiting
A Multicenter, Prospective, Randomized Trial of the Efficacy and Safety of the Postoperative Adjuvant Treatment in Patients With High-risk Stage I Endometrial Carcinoma [NCT01820858]Phase 3300 participants (Anticipated)Interventional2012-11-30Active, not recruiting
A Phase II Study of the Efficacy and Safety of Lenalidomide Plus ICE in the Treatment of Refractory and Relapsed Diffuse Large B-cell Lymphoma [NCT03367143]Phase 239 participants (Anticipated)Interventional2016-12-31Active, not recruiting
Almonertinib Alone Versus Almonertinib Plus Chemotherapy as First-Line Treatment in Locally Advanced Or Metastatic NSCLC Patients With Concomitant EGFR and Tumor Suppressor Gene Mutation: A Multicenter, Open-Label, Randomized, Controlled Phase III Study ( [NCT04500717]Phase 3460 participants (Anticipated)Interventional2020-10-31Not yet recruiting
A Study on Neoadjuvant Therapy for Her-2 Positive Breast Cancer and the Prognosis Detecting Circulating Tumor Cells [NCT02510781]Phase 2200 participants (Anticipated)Interventional2015-01-31Recruiting
Feasability of an Unique Intraoperative Given Hyperthermal Intraperitoneal Chemotherapy With Carboplatin During a Secondary Cytoreductive Operation in Patients With Platinum-sensitive Recurrence of Ovarian Carcinoma [NCT02487849]Phase 20 participants (Actual)Interventional2016-08-31Withdrawn(stopped due to actually limited personnel ressources)
A Phase II Study to Evaluate Camrelizumab With Pemetrexed / Carboplatin in Patients With Brain Metastases of Driven Gene-negative, Non-squamous Non-small Cell Lung Cancer [NCT04211090]Phase 245 participants (Actual)Interventional2020-01-15Active, not recruiting
Pulsed Low Dose Rate Radiation With Concurrent Chemotherapy for Non-Small Cell Lung Cancer and Esophageal Cancer [NCT03094884]Phase 140 participants (Anticipated)Interventional2017-02-24Recruiting
A Phase I/II Study of Carboplatin/Nab-Paclitaxel and Pembrolizumab for Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT02382406]Phase 1/Phase 246 participants (Actual)Interventional2015-06-04Terminated(stopped due to The study was completed. It was fully accrued.)
A Randomized, Phase III Study Comparing Carboplatin/Paclitaxel or Carboplatin/Paclitaxel/Bevacizumab With or Without Concurrent Cetuximab in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) [NCT00946712]Phase 31,333 participants (Actual)Interventional2009-07-15Terminated(stopped due to terminated at pre-planned futility analysis)
The Use and Safety of Metformin, Carboplatin and Paclitaxel in Non-Diabetic Patients With Recurrent, Platinum Sensitive Ovarian Cancer and the Feasibility of Using a Core Biopsy for RNA-Seq [NCT02050009]Phase 10 participants (Actual)InterventionalWithdrawn(stopped due to study was never opened to accrual)
A Phase 1, Multicenter, Open-Label Study to Determine the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of Combinations of ABBV-927 With ABBV-368, Budigalimab (ABBV-181) and/or Chemotherapy in Subjects With Locally Advanced or Metastati [NCT03893955]Phase 1150 participants (Anticipated)Interventional2019-05-21Active, not recruiting
A Phase 1 Study of Chloroquine in Combination With Carboplatin/Gemcitabine in Advanced Solid Tumors [NCT02071537]Phase 124 participants (Actual)Interventional2014-05-13Completed
Master Protocol: A Phase 2, Open-label, Multi-arm Study of Tislelizumab in Combination With Investigational Agents With or Without Chemotherapy in Patients With Previously Untreated, Locally Advanced, Unresectable, or Metastatic Non-Small Cell Lung Cancer [NCT05635708]Phase 2200 participants (Anticipated)Interventional2023-03-07Recruiting
A Phase I/II Trial of PARP Inhibition, Radiation, and Immunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer (ES-SCLC) - PRIO Trial [NCT04728230]Phase 1/Phase 263 participants (Anticipated)Interventional2021-01-05Recruiting
Phase II Trial of Sintilimab, an Anti-PD-1 Monoclonal Antibody, in Combination With Carboplatin and Nab-paclitaxel , as a Novel Neoadjuvant Pre-Surgical Therapy for Oral Cavity or Oropharyngeal Squamous Cell Carcinoma [NCT04718415]Phase 251 participants (Anticipated)Interventional2021-01-23Recruiting
A Prospective, Single Center, Randomized, Open-labled Stage III Clinical Trial Comparing the Efficacy and Safety of Anthracyclin Followed by Weekly Paclitaxel Versus Dose-dense Anthracyclin Followed by Weekly Paclitaxel Versus Dose-dense Anthracyclin Foll [NCT04296175]Phase 3808 participants (Anticipated)Interventional2020-03-05Recruiting
A Phase III, Randomized, Double-Blind Study of Bevacizumab, Carboplatin, and Paclitaxel or Pemetrexed With or Without Atezolizumab in Chemotherapy-Naïve Patients With Stage IV Non-Squamous Non-Small Cell Lung Cancer (IMpower151) [NCT04194203]Phase 3304 participants (Actual)Interventional2020-04-09Active, not recruiting
KEYMAKER-U01 Substudy 1: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab in Combination With Chemotherapy in Treatment-Naive Patients With Advanced Non-small Cell Lung Cancer (NSCLC) [NCT04165070]Phase 2360 participants (Anticipated)Interventional2019-12-19Active, not recruiting
A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Chemotherapy Plus Placebo for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer (KEYNOTE-826) [NCT03635567]Phase 3617 participants (Actual)Interventional2018-10-25Active, not recruiting
MITO END-3: A Randomized Phase II Trial of Carboplatin+Paclitaxel Compared to Carboplatin+Paclitaxel+Avelumab in Advanced (Stage III-IV) or Recurrent Endometrial Cancer [NCT03503786]Phase 2125 participants (Actual)Interventional2018-04-01Active, not recruiting
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Immunotherapy-Based Treatment Combinations In Patients With Metastatic Non-Small Cell Lung Cancer (Morpheus-Lung) [NCT03337698]Phase 1/Phase 2470 participants (Anticipated)Interventional2018-01-02Recruiting
A Phase 1 Study of RGX-104, a Small Molecule LXR Agonist, as a Single Agent and as Combination Therapy in Patients With Advanced Solid Malignancies and Expansion in Select Malignancies [NCT02922764]Phase 1150 participants (Anticipated)Interventional2016-11-30Recruiting
Randomized Phase II Study of Carboplatin and Paclitaxel +/- Cetuximab, in Advanced and/or Recurrent Cervical Cancer [NCT00997009]Phase 2108 participants (Anticipated)Interventional2009-10-31Active, not recruiting
Liposomal Doxorubicin Versus Carboplatin/Paclitaxel in Patients With Ovarian Cancer Recurrence Between 6 and 12 Months After Previous Platinum Based Therapy: Phase III Randomized Multicenter Study Amendment Title Protocol Version 2.0: Phase III Internatio [NCT00657878]Phase 3215 participants (Actual)Interventional2008-11-30Active, not recruiting
A Phase 1b Dose Escalation Study of OMP-54F28 in Combination With Paclitaxel and Carboplatin in Patients With Recurrent Platinum-Sensitive Ovarian Cancer [NCT02092363]Phase 137 participants (Actual)Interventional2014-01-31Completed
A RANDOMIZED, OPEN-LABEL, MULTICENTER, PHASE 3 STUDY TO EVALUATE THE EFFICACY AND SAFETY OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AND/OR FOLLOWING CHEMOTHERAPY IN PATIENTS WITH PREVIOUSLY UNTREATED EPITHELIAL OVARIAN CANCER JAVELIN OVARIAN 100 [NCT02718417]Phase 3998 participants (Actual)Interventional2016-05-19Terminated(stopped due to The study was terminated based on the results of a planned interim analysis that showed futility of efficacy.)
"Cyclin dEpendent Kinase in tRiple nEGatIVe brEast canceR - a Window of Opportunity Study" [NCT05067530]Phase 2126 participants (Anticipated)Interventional2022-01-01Not yet recruiting
Phase II Trial of Pembrolizumab in Combination With ICE Salvage Chemotherapy for Relapsed/Refractory Hodgkin Lymphoma [NCT03077828]Phase 243 participants (Actual)Interventional2017-04-21Active, not recruiting
A Phase I Study of Pioglitazone and Carboplatin in Patients With Advanced Solid Tumors [NCT02133625]Phase 128 participants (Anticipated)Interventional2011-08-31Completed
A Phase III Study Comparing Two Carboplatin Containing Regimens for Children and Young Adults With Previously Untreated Low Grade Glioma [NCT02455245]Phase 3160 participants (Anticipated)Interventional2015-03-31Recruiting
QUILT-2.024: Phase 2 Neoadjuvant, Consolidation, and Adjuvant Combination NANT Immunotherapy Versus Standard of Care in Subjects With Resectable Non-small Cell Lung Cancer [NCT03574649]Phase 20 participants (Actual)Interventional2018-09-30Withdrawn(stopped due to Trial not initiated)
A Randomized Phase II Study of MCS110 Combined With Carboplatin and Gemcitabine in Advanced Triple Negative Breast Cancer (TNBC) [NCT02435680]Phase 250 participants (Actual)Interventional2015-08-10Completed
Combination of Induction Durvalumab and Tremelimumab Alone Versus Durvalumab and Tremelimumab With Chemotherapy for Potentially Resectable Pleural Mesothelioma [NCT05932199]Phase 1/Phase 252 participants (Anticipated)Interventional2023-09-30Not yet recruiting
A Phase 2 Study of Evorpacept (ALX148) in Combination With Pembrolizumab and Chemotherapy in Patients With Advanced Head and Neck Squamous Cell Carcinoma (ASPEN-04) [NCT04675333]Phase 2168 participants (Anticipated)Interventional2021-05-10Recruiting
Pilot Study of Induction Chemotherapy Followed by Risk and Response-Stratified Treatment for Locoregional HPV Associated Oropharyngeal Cancer [NCT04572100]Phase 150 participants (Actual)Interventional2020-10-01Completed
A Phase II Randomized Study: Outcomes After Secondary Cytoreductive Surgery With or Without Carboplatin Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Followed by Systemic Combination Chemotherapy for Recurrent Platinum-Sensitive Ovarian, Fallopian Tub [NCT01767675]Phase 299 participants (Actual)Interventional2013-01-08Active, not recruiting
Randomized Phase III Study of Maintenance Therapy With Bevacizumab, Pemetrexed, or a Combination of Bevacizumab and Pemetrexed Following Carboplatin, Paclitaxel and Bevacizumab for Advanced Non-Squamous NSCLC [NCT01107626]Phase 31,516 participants (Actual)Interventional2010-10-25Completed
A Phase II Study of L-BLP25 and Bevacizumab in Unresectable Stage IIIA and IIIB Non-Squamous Non-Small Cell Lung Cancer After Definitive Chemoradiation [NCT00828009]Phase 270 participants (Actual)Interventional2011-01-17Completed
Atezolizumab, Pertuzumab and Trastuzumab With Chemotherapy as Neoadjuvant Treatment of HER2 Positive Early High-risk and Locally Advanced Breast Cancer (APTneo) [NCT03595592]Phase 3650 participants (Anticipated)Interventional2018-09-07Active, not recruiting
Neo-Adjuvant Study With the PDL1-directed Antibody in Triple Negative Locally Advanced Breast Cancer Undergoing Treatment With Nab-paclitaxel and Carboplatin [NCT02620280]Phase 3278 participants (Actual)Interventional2016-04-30Active, not recruiting
A Multicenter, Randomized, Open-label, Phase III Trial to Assess Efficacy and Safety of Cetuximab When Given in Combination With Cisplatin Plus 5 Fluorouracil Versus Cisplatin Plus 5-fluorouracil Alone for the First-line Treatment of Chinese Subjects With [NCT02383966]Phase 3243 participants (Actual)Interventional2015-07-31Completed
A Phase I Image-Guided Adaptive Radiotherapy Study Using Active Breathing Control (ABC) and Simultaneous Integrated Boost for Patients With Inoperable Non-Small Cell Lung Cancer [NCT02059967]Phase 10 participants (Actual)Interventional2014-03-31Withdrawn(stopped due to Due to no accrual.)
Erlotinib Treatment Beyond Progression in EGFR Mutant or Patients Who Have Responded EGFR TKI in Stage IIIB/IV NSCLC [NCT02064491]Phase 218 participants (Actual)Interventional2014-02-28Completed
An Open-label, Phase 2 Randomized Trial of Camrelizumab (SHR1210) Plus Apatinib Versus Paclitaxel and Cisplatin/Carboplatin Plus Bevacizumab as a First-line Therapy in Patients With Stage IVB, Recurrent, or Persistent Cervical Cancer [NCT04974944]Phase 2172 participants (Anticipated)Interventional2021-07-30Recruiting
Phase Ib Study of the Combination of BKM120 and Cisplatin or Carboplatin in Patients With Advanced Solid Tumors [NCT02439489]Phase 134 participants (Actual)Interventional2012-12-31Completed
A Phase 1b Study to Evaluate Safety and Clinical Activity of Pembrolizumab (MK-3475) in Combination With Chemotherapy as Neoadjuvant Treatment for Triple Negative Breast Cancer (TNBC) - (KEYNOTE 173) [NCT02622074]Phase 160 participants (Actual)Interventional2016-01-27Completed
A Phase Ib, Dose Finding Study Evaluating AZD1775 in Monotherapy, in Combination With Carboplatin and Paclitaxel, and in Combination With Only Carboplatin in Adult Asian Patients With Advanced Solid Tumours [NCT02341456]Phase 119 participants (Actual)Interventional2015-01-16Completed
Multi-center, Randomized, Controlled, Open-label Study of Bevacizumab With Carboplatin and Paclitaxel Versus Carboplatin and Paclitaxel in Patients With Metastatic Nasopharyngeal Carcinoma [NCT02250599]Phase 280 participants (Anticipated)Interventional2014-08-31Recruiting
Efficacy of Carboplatin and Paclitaxel With Trastuzumab and Pertuzumab (wPCbTP) and Switching to an Anthracycline-based Regimen (AC) in Non-responding Patients in Clinical Stage I-III HER2-positive Breast Cancer. [NCT02789657]Phase 232 participants (Actual)Interventional2016-11-21Completed
Shorter Anthracycline-Free Chemo Immunotherapy Adapted to Pathological Response in Early Triple Negative Breast Cancer (SCARLET), A Randomized Phase III Study [NCT05929768]Phase 32,400 participants (Anticipated)Interventional2023-09-15Recruiting
The BARCODE 2 Study - The Use of Genetic Profiling to Guide Prostate Cancer Treatment [NCT02955082]Phase 2450 participants (Anticipated)Interventional2017-05-25Recruiting
A Prospective, Single-arm, Phase II Study of PD-1 Inhibitor Combined With Ifosfamide, Carboplatin, and Etoposide (ICE) in the Treatment of Relapsed/Refractory Gray Area Lymphoma [NCT04860674]Phase 220 participants (Anticipated)Interventional2021-05-01Not yet recruiting
Penpulimab-based Combination Neoadjuvant/Adjuvant Therapy for Patients With Resectable Locally Advanced Non-small Cell Lung Cancer: a Phase II Clinical Study (ALTER-L043) [NCT04846634]Phase 290 participants (Anticipated)Interventional2021-08-31Not yet recruiting
A Phase II Trial of Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma: BENCART Trial [NCT02424045]Phase 230 participants (Actual)Interventional2015-05-31Completed
A Randomized, Multicenter,Open-label Phase II Study is to Evaluate the Effects of Chemotherapy and Sintilimab or in Combination With Autologous Cytokine-induced Killer Cell Immunotherapy in Patients With Stage IV Non-small-cell Lung Cancer [NCT04836728]Phase 2156 participants (Anticipated)Interventional2021-04-01Not yet recruiting
A Prospective, Single-arm, Multicenter, Exploratory Phase II Study to Evaluate the Efficacy and Safety of Anlotinib Combined With Carboplatin/Paclitaxel as First-line Treatment in Patients With Advanced Ovarian Cancer [NCT04807166]Phase 256 participants (Anticipated)Interventional2021-06-01Not yet recruiting
A Phase 1b/2, Open-label, Randomized Study of Vudalimab in Combination With Chemotherapy or Pembrolizumab in Combination With Chemotherapy as First-line Treatment in Patients With Advanced Non-small Cell Lung Cancer [NCT06173505]Phase 1/Phase 2168 participants (Anticipated)Interventional2023-12-31Not yet recruiting
A Phase 3 Study of Dinutuximab Added to Intensive Multimodal Therapy for Children With Newly Diagnosed High-Risk Neuroblastoma [NCT06172296]Phase 3478 participants (Anticipated)Interventional2024-02-14Not yet recruiting
Efficacy and Safety of Cadonilimab (AK104) Plus Chemotherapy in the Treatment of Recurrent or Advanced Endometrial Cancer: a Multicenter, Prospective Phase II Trial [NCT06066216]Phase 245 participants (Anticipated)Interventional2023-12-15Not yet recruiting
A Randomized, Open-Label, Phase 3 Study to Evaluate Zimberelimab and Domvanalimab in Combination With Chemotherapy Versus Pembrolizumab With Chemotherapy for the First-Line Treatment of Patients With Metastatic Non-Small Cell Lung Cancer With No Epidermal [NCT05502237]Phase 3720 participants (Anticipated)Interventional2022-10-12Recruiting
A Randomized, Double-blind, Multi-center, Phase III Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment [NCT05184712]Phase 3470 participants (Anticipated)Interventional2022-01-01Recruiting
Phase 2 Randomized Trial of Neoadjuvant or Palliative Chemotherapy With or Without Immunotherapy for Peritoneal Mesothelioma [NCT05001880]Phase 266 participants (Anticipated)Interventional2022-03-22Recruiting
N9: Pilot Study of Novel Shortened Induction Chemotherapy for High-Risk Neuroblastoma [NCT04947501]Early Phase 130 participants (Anticipated)Interventional2021-06-22Recruiting
A Phase 1/2a, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, and Preliminary Efficacy of Subcutaneous Durvalumab in Patients With Non-Small Cell and Small Cell Lung Cancer - SCope-D1 [NCT04870112]Phase 118 participants (Actual)Interventional2021-06-28Completed
Phase I/II Study of Stereotactic Radiosurgery With Concurrent Administration of DNA Damage Response (DDR) Inhibitor (OLAparib) Followed by Adjuvant Combination of DuRvalumab (MEDI4736) and Physician's Choice Systemic Therapy in Subjects With BreAst Cancer [NCT04711824]Phase 1/Phase 241 participants (Anticipated)Interventional2022-03-09Recruiting
A Phase 2 Study of MLN4924 (Pevonedistat) in Combination With Carboplatin and Paclitaxel in Advanced NSCLC Previously Treated With Immunotherapy [NCT03965689]Phase 227 participants (Actual)Interventional2019-09-03Active, not recruiting
A Pilot Study of Immunotherapy Including Haploidentical NK Cell Infusion Following CD133+ Positively-Selected Autologous Hematopoietic Stem Cells in Children With High Risk Solid Tumors or Lymphomas [NCT02130869]Phase 18 participants (Actual)Interventional2014-10-10Completed
A Non-inferior, Randomized Controlled Phase III Clinical Study Comparing the Efficacy of TCbHPand ECHP-THP in Neoadjuvant Treatment of Operable HER2-positive Breast Cancer [NCT05474690]Phase 3456 participants (Anticipated)Interventional2022-05-11Recruiting
Multicenter Prospective Randomized Study on NeoAdjuvant Chemotherapy Followed by Radical Hysterectomy (OP) Versus Primary Chemo-RADiation in Patients With Cervical Cancer FIGO Stage IB2 and IIB [NCT02422563]Phase 3534 participants (Anticipated)Interventional2015-10-31Not yet recruiting
A Phase I Study of Xevinapant With Radiation and Concurrent Carboplatin and Paclitaxel in Patients Ineligible for Cisplatin With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT06110195]Phase 142 participants (Anticipated)Interventional2023-12-31Not yet recruiting
A Phase II, Single Arm Study of Chemoimmunotherapy for the Treatment of Men With Neuroendocrine or Aggressive Variant Metastatic Prostate Cancer (CHAMP) [NCT04709276]Phase 243 participants (Anticipated)Interventional2021-06-07Recruiting
An Open-label, Non-randomized Phase 2 Study of Ofatumomab (O) in Combination With ICE (Ifosfamide, Carboplatin, Etoposide)-Chemotherapy in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) [NCT02412267]Phase 217 participants (Actual)Interventional2011-04-30Completed
A Multi-center, Randomized, Double-blind, Parallel, Two-group Phase III Clinical Study of the Efficacy and Safety of QL1101 and Avastin® Respectively Combined With Paclitaxel and Carboplatin in the First-line Treatment of Non-squamous Non-small Cell Lung [NCT03169335]Phase 3535 participants (Actual)Interventional2017-03-28Completed
PiSARRO: p53 Suppressor Activation in Recurrent High Grade Serous Ovarian Cancer, a Phase Ib/II Study of Systemic Carboplatin Combination Chemotherapy With or Without APR-246 [NCT02098343]Phase 1/Phase 2247 participants (Actual)Interventional2014-03-31Completed
Immuno-Chemotherapy as Single Treatment Modality for Larynx Preservation (ICoLP) [NCT04030455]Phase 225 participants (Anticipated)Interventional2019-08-07Recruiting
Phase I Study of Osimertinib+Bevacizumab+Carboplatin and Pemetrexed for Untreated Patients With EGFR Mutation Advanced Non-squamous Non-Small Cell Lung Cancer With Concomitant Mutations. [NCT05507606]Phase 250 participants (Anticipated)Interventional2021-08-01Recruiting
A Multicenter Randomized Phase Ⅲ Clinical Trial of Gemcitabine in Combination With Capecitabine Versus Gemcitabine Plus Carboplatin as First-line Treatment in Triple-negative Recurrent or Metastatic Breast Cancer [NCT02207335]Phase 3120 participants (Anticipated)Interventional2013-12-31Recruiting
Phase I/II Study of PEGylated Arginine Deiminase (ADI-PEG20) With Carboplatin and Cabazitaxel in Men With Aggressive Variant Prostate Cancers (AVPC) [NCT06085729]Phase 1/Phase 230 participants (Anticipated)Interventional2024-03-01Not yet recruiting
CASPIAN-RT Trial: Hypofractionated Consolidative Radiation Therapy After Durvalumab (MEDI4736) Plus Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer [NCT05161533]Phase 20 participants (Actual)Interventional2023-10-19Withdrawn(stopped due to Closed per SRC Low Accrual Policy. Study closed prior to any participants enrolled.)
Phase II Multicentre, Randomized, Open-label Study to Evaluate the Safety and Efficacy of Avelumab With Gemcitabine/Carboplatin Versus Gemcitabine/Carboplatin Alone in Patients With Unresectable or Metastatic Urothelial Carcinoma (UC) Who Have Not Receive [NCT03390595]Phase 285 participants (Actual)Interventional2018-05-17Completed
A Study of Enfortumab Vedotin (ASG-22CE) as Monotherapy or in Combination With Other Anticancer Therapies for the Treatment of Urothelial Cancer [NCT03288545]Phase 1/Phase 2348 participants (Actual)Interventional2017-10-11Active, not recruiting
An Open Label, Dose Escalation Followed by Dose Expansion, Safety and Tolerability Trial of CAN04, a Fully Humanized Monoclonal Antibody Against IL1RAP, in Subjects With Solid Malignant Tumors [NCT03267316]Phase 1/Phase 2167 participants (Actual)Interventional2017-09-19Active, not recruiting
A Randomized, Placebo-Controlled, Phase 2 Study of Docetaxel and Cisplatin/Carboplatin With or Without Erlotinib in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck [NCT01064479]Phase 2123 participants (Actual)Interventional2010-02-05Completed
Protocol for the Study and Treatment of Participants With Intraocular Retinoblastoma [NCT01783535]Phase 2174 participants (Anticipated)Interventional2013-06-19Active, not recruiting
A Randomized, Double-Blind, Multicenter, Phase Ⅲ Study of Anlotinib Hydrochloride Capsule Combined With Chemotherapy Versus Placebo Combined With Chemotherapy in Subjects With Squamous Non-small Cell Lung Cancer [NCT04073537]Phase 3386 participants (Anticipated)Interventional2019-10-31Not yet recruiting
Phase II Study of Concurrent Carboplatin, Pemetrexed, and Radiotherapy for Limited Stage of Small Cell Lung Cancer [NCT00494026]Phase 24 participants (Actual)Interventional2007-09-30Terminated(stopped due to Study stopped early based on interim results of another trial, showing inferior activity of pemetrexed/carboplatin compared to etoposide/carboplatin in SCLC.)
Safety and Efficacy of Four Courses of Pembrolizumab Combined With Carboplatin and Albumin-binding Paclitaxel Versus Two Courses of Neoadjuvant Therapy in Patients With Resectable Head and Neck Squamous Cell Carcinoma (T3 or T4, N0) : An Optimal Efficacy [NCT05980702]Phase 2192 participants (Anticipated)Interventional2023-04-04Recruiting
A Phase II Study of Platinum and Etoposide Chemotherapy, Durvalumab With Thoracic Radiotherapy in the First Line Treatment of Patients With Extensive-stage Small-cell Lung Cancer [NCT05796089]Phase 235 participants (Anticipated)Interventional2022-01-01Recruiting
RAGE Inhibition to Decrease Cancer Therapy Related Cardio Toxicity in Women With Early Breast Cancer [NCT05256745]Phase 1/Phase 248 participants (Anticipated)Interventional2023-06-06Recruiting
A Randomized Phase II Study of Neo-adjuvant Chemo/Immunotherapy Versus Chemotherapy Alone for the Treatment of Locally Advanced and Potentially Resectable Non-small Cell Lung Cancer (NSCLC) Patients. [NCT03838159]Phase 290 participants (Actual)Interventional2019-05-15Active, not recruiting
A Phase III Trial Evaluating the Addition of Trastuzumab to Trimodality Treatment of HER2-Overexpressing Esophageal Adenocarcinoma [NCT01196390]Phase 3203 participants (Actual)Interventional2011-02-14Completed
Phase II Pharmacological Study With Wee-1 Inhibitor MK-1775 Combined With Carboplatin in Patients With p53 Mutated Epithelial Ovarian Cancer and Early Relapse (< 3 Months) or Progression During Standard First Line Treatment With an Additional Safety and P [NCT01164995]Phase 224 participants (Actual)Interventional2010-07-31Completed
A Randomized Phase II Study of Gemcitabine and Carboplatin With or Without MK-0646 as First-Line Therapy in Advanced Squamous Non-Small Cell Lung Carcinoma [NCT00951444]Phase 20 participants (Actual)InterventionalWithdrawn(stopped due to The study was not activated.)
A Phase II Evaluation of Paclitaxel (Taxol, NSC # 673089) and Carboplatin (Paraplatin, NSC #241240) in the Treatment of Advanced, Persistent, or Recurrent Uterine Carcinosarcoma [NCT00112489]Phase 255 participants (Actual)Interventional2005-05-31Completed
A Phase II/III Study to Evaluate the Safety and Efficacy of Combretastatin A-4 Phosphate in Combination With Paclitaxel and Carboplatin in Comparison With Paclitaxel and Carboplatin Against Anaplastic Thyroid Carcinoma [FACT] [NCT00507429]Phase 2/Phase 380 participants (Actual)Interventional2007-08-31Terminated(stopped due to Low rate of subject accrual)
A Single Arm Trial of Adjuvant Pembrolizumab in Patients With Limited Stage Small Cell Lung Cancer [NCT06140407]Phase 220 participants (Anticipated)Interventional2023-12-31Not yet recruiting
(TESSERACT): Phase I/II Trial in ES-SCLC to Enhance Response to Atezolizumab Plus Chemotherapy With Total Body Irradiation (TBI) [NCT06110572]Phase 1/Phase 218 participants (Anticipated)Interventional2024-01-31Recruiting
A Phase I/II, Open-Label, Single-Arm, Two-Part Trial to Evaluate Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of Glofitamab in Monotherapy and in Combination With Chemoimmunotherapy in Pediatric and Young Adult Participants With Relapse [NCT05533775]Phase 1/Phase 265 participants (Anticipated)Interventional2022-11-16Recruiting
A Phase 2, Open-Label, Parallel Cohort Study of Subcutaneous Amivantamab in Multiple Regimens in Patients With Advanced or Metastatic Solid Tumors Including EGFR-mutated Non-Small Cell Lung Cancer [NCT05498428]Phase 2390 participants (Anticipated)Interventional2022-11-11Recruiting
Randomized Phase I Study Assessing the Safety and Tolerability Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at Completion of Interval Cytoreductive Surgery Compared to Surgery and Chemotherapy Prior to Surgery for Patients With Stage III/IV Ovarian C [NCT05415709]Early Phase 145 participants (Anticipated)Interventional2022-06-13Recruiting
A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants With Metastatic Nonsqu [NCT04716933]Phase 3201 participants (Actual)Interventional2019-11-05Active, not recruiting
A Randomized, Open-label Phase 2 Clinical Trial of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer [NCT04702880]Phase 2120 participants (Anticipated)Interventional2021-03-17Recruiting
Olaparib in Combination With Pembrolizumab and Carboplatin as First-Line Treatment of Recurrent or Metastatic Head and Neck Squamous-Cell Carcinoma: A Single-Arm, Phase 2 Trial [NCT04643379]Phase 230 participants (Actual)Interventional2021-08-07Active, not recruiting
A Phase III, Open-label, Randomized Study of Osimertinib With or Without Platinum Plus Pemetrexed Chemo, as First-line Treatment in Patients With Epidermal Growth Factor Receptor (EGFR) Mutation Positive, Locally Advanced or Metastatic Non-small Cell Lung [NCT04035486]Phase 3587 participants (Actual)Interventional2019-07-02Active, not recruiting
A Phase II, Randomized, Active-Controlled, Multi-Center Study Comparing the Efficacy and Safety of Targeted Therapy or Cancer Immunotherapy Guided by Genomic Profiling Versus Platinum-Based Chemotherapy in Patients With Cancer of Unknown Primary Site Who [NCT03498521]Phase 2790 participants (Anticipated)Interventional2018-07-10Active, not recruiting
A Rollover Study to Provide Continued Treatment With M6620 [NCT03309150]Phase 11 participants (Actual)Interventional2018-01-10Active, not recruiting
A Two-arm (Phase 2) Exploratory Study of Nivolumab Monotherapy or in Combination With Nab-paclitaxel and Carboplatin in Early Stage NSCLC in China [NCT04015778]Phase 248 participants (Anticipated)Interventional2019-08-08Recruiting
Vinorelbine Plus Gemcitabine (VG) Versus Vinorelbine Plus Carboplatin (VC) in Advanced Non-small Cell Lung Cancer. An Open Randomized Multicenter Phase III Trial From Norwegian Lung Cancer Study Group (NLCG) [NCT00737867]Phase 3444 participants (Anticipated)Interventional2007-09-30Completed
Phase III Randomized, Placebo Controlled Study of Sorafenib in Repeated Cycles of 21 Days in Combination With Paclitaxel/Carboplatin Chemotherapy in Subjects With Unresectable Stage III or Stage IV Melanoma. [NCT00111007]Phase 3270 participants (Actual)Interventional2005-05-31Completed
A Phase I Study of ASA 404 in Combination With Carboplatin/Paclitaxel/Cetuximab in Patients With Refractory Solid Tumors [NCT01031212]Phase 10 participants (Actual)Interventional2010-01-31Withdrawn(stopped due to The investigator has left the institution (UCSF) prior to study start-up)
Phase I/ II Trial of Carboplatin and Etoposide Plus LBH589 for Previously Untreated Extensive Stage Small Cell Lung Cancer [NCT00958022]Phase 17 participants (Actual)Interventional2009-09-30Terminated(stopped due to Based on the tolerabilty challenges of the combination)
A Phase 2 Study to Evaluate the Efficacy and Safety of Palifermin (Recombinant Human Keratinocyte Growth Factor) in the Reduction of Dysphagia in Patients Receiving Concurrent Chemoradiotherapy Followed by Consolidation Chemotherapy for Locally Advanced N [NCT00094861]Phase 2100 participants (Actual)Interventional2005-01-31Completed
Therapy-Optimization Trial and Phase II Study for the Treatment of Relapsed or Refractory of Primitive Neuroectodermal Brain Tumors and Ependymomas in Children and Adolescents [NCT00749723]Phase 2/Phase 3174 participants (Actual)Interventional2006-02-01Completed
A Phase II Multicenter Trial of Paclitaxel and Carboplatin in Women With Advanced (IIIb, IIIc, IVa and IVb) or Recurrent (All Stages) Malignant Mixed Mullerian Tumors (MMMT) of the Uterus [NCT00502203]Phase 223 participants (Actual)Interventional2001-08-31Completed
A Phase II Study of Weekly Dose-Dense Nanoparticle Paclitaxel (ABI-007), Carboplatin With Herceptin® As First-Line Therapy of Advanced HER-2 Positive Breast Cancer [NCT00093145]Phase 232 participants (Actual)Interventional2004-06-01Completed
"A Randomized Multicenter Phase II Trial to Evaluate the Effectiveness of Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients" [NCT00432172]Phase 2189 participants (Actual)Interventional2007-04-24Completed
Atezolizumab With Platinum and Etoposide Chemotherapy Followed by Cystectomy for Patients With Localized Small Cell Neuroendocrine Bladder Cancer [NCT05312671]Phase 263 participants (Anticipated)Interventional2022-06-27Recruiting
A Phase III Clinical Trial of Adjuvant Chemotherapy vs Chemoimmunotherapy for Stage IB-IIIA Completely Resected Non-small Cell Lung Cancer (NSCLC) Patients. [NCT04564157]Phase 3210 participants (Anticipated)Interventional2021-01-13Recruiting
Safety and Efficacy of High Dose Inorganic seLenium for Preventing Chemotherapy Induced pEripheral Neuropathy in platINUM Sensitive Recurrent Ovarian, Fallopian, Primary Peritoneal Cancer: Phase III Randomised Controlled Trial [NCT04201561]Phase 368 participants (Anticipated)Interventional2019-12-24Active, not recruiting
Reduced Intensity Radio-chemotherapy for Stage IIA/B Seminoma. A Multicenter, Open Label Phase II Trial With Two Cohorts [NCT03937843]Phase 2135 participants (Actual)Interventional2019-07-29Active, not recruiting
A Phase II Multi-Institutional Trial of Focal Radiotherapy With Concomitant Carboplatin as a Radiosensitizer and the Prospective Analysis of Survivin, an Inhibitor of Apoptosis, as a Biomarker in Children With Newly Diagnosed Non-Metastatic Ependymoma and [NCT01088035]Phase 275 participants (Anticipated)Interventional2010-04-30Terminated(stopped due to Poor accrual)
A Phase 1b, Open-Label, Dose-Escalation Study of BIIB022 in Combination With Paclitaxel and Carboplatin in Subjects With Treatment-Naive, Stage IIIB/IV Non-Small Cell Lung Cancer [NCT00970580]Phase 118 participants (Actual)Interventional2009-10-31Completed
A Pilot Study to Evaluate Response to Neoadjuvant Chemotherapy With Cisplatin and Docetaxel Followed by Chemoradiation Therapy With Carboplatin in Stage IV Non-metastatic Head and Neck Cancer [NCT00982436]Phase 1/Phase 237 participants (Anticipated)Interventional2009-09-30Recruiting
A Phase 2 Study of Intravenous Administration of REOLYSIN (Reovirus Type 3 Dearing) in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma [NCT00984464]Phase 214 participants (Actual)Interventional2009-09-30Completed
A Randomized Phase II Trial to Assess the Predictive Value of Increased EGFR Copy Number by FISH in Patients With Advanced / Metastatic NSCLC Treated With Cetuximab and Carboplatin / Paclitaxel [NCT00768131]Phase 20 participants (Actual)Interventional2008-10-31Withdrawn
Randomised, Double-Blinded, Placebo Controlled, Phase 2 Study of CS-1008 in Combination With Carboplatin/Paclitaxel in Chemotherapy naïve Subjects With Metastatic or Unresectable Non-small Cell Lung Cancer [NCT00991796]Phase 2109 participants (Actual)Interventional2009-06-30Completed
A Phase 2 Study of Intravenous Administration of REOLYSIN® (Reovirus Type 3 Dearing) in Combination With Paclitaxel and Carboplatin in Patients With Squamous Cell Carcinoma of the Lung [NCT00998192]Phase 232 participants (Actual)Interventional2009-10-31Completed
A Phase II Selection Design of Pharmacodynamic Separation of Carboplatin/Paclitaxel/OSI-774 (Erlotinib; NSC-718781) or OSI-774 Alone in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients With Performance Status 2 (PS-2) [NCT00661193]Phase 259 participants (Actual)Interventional2008-12-31Completed
NMES for Patients With NSCLC Receiving Palliative Chemotherapy. Is Neuromuscular Electrical Stimulation an Acceptable and Feasible Supportive Therapy for Patients With Non-Small Cell Lung Cancer Receiving Palliative Chemotherapy? [NCT01097317]Phase 252 participants (Anticipated)Interventional2009-09-30Recruiting
Phase I Trial of Carboplatin and Etoposide in Combination With Everolimus (RAD001) in Advanced Solid Tumors, With Emphasis on Small Cell Lung Cancer (SCLC) [NCT00807755]Phase 15 participants (Actual)Interventional2009-03-31Terminated(stopped due to Number of known toxicities observed despite a treatment-naïve population)
A Phase II Study to Assess the Safety and Efficacy of the Combination of Carboplatin, Paclitaxel, and Bevacizumab ± Combretastatin A4 Phosphate (CA4P) Followed by Bevacizumab ± CA4P in Subjects With Chemotherapy Naïve Stage IIIB/IV Non-Squamous Cell Histo [NCT00653939]Phase 263 participants (Actual)Interventional2008-03-31Completed
Releasing the Cancer Patient's Immune System From Down-regulation With Timed Delivery of Standard Chemotherapy [NCT00568451]Phase 212 participants (Actual)Interventional2006-06-30Terminated(stopped due to Slow accrual.)
Phase II Study Evaluating PegLiposomal Doxorubicin (PLD) and Carboplatin Combination Chemotherapy in Gynecological Sarcomas and Mixed Epithelial-Mesenchymal Tumors [NCT00815945]Phase 241 participants (Actual)Interventional2008-06-30Completed
An Open-label, Multicenter, Phase II Clinical Study to Evaluate the Efficacy and Safety of HLX07 (Recombinant Humanized Anti-EGFR Monoclonal Antibody Injection) + HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) + Chemotherapy in Pati [NCT05354700]Phase 220 participants (Anticipated)Interventional2023-03-29Not yet recruiting
A Phase I, Open-Label, Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending Doses of AZD0530 in Combination With Carboplatin and Paclitaxel Chemotherapy in Japanese Patients With Advanced Solid Malignancies [NCT01000896]Phase 127 participants (Anticipated)Interventional2010-01-31Withdrawn(stopped due to AstraZeneca has discontinued the development of AZD0530. No new AstraZeneca-sponsored clinical studies will be initiated..)
A Randomized Phase II Trial of Temozolomide (TMZ) and Bevacizumab or ABI-007 (ABX)/Carboplatin (CBDCA) and Bevacizumab in Patients With Unresectable Stage IV Malignant Melanoma [NCT00626405]Phase 295 participants (Actual)Interventional2008-08-31Completed
[A Prospective, Randomized Trial to Assess the Added Value of Concomitant Modulated Electro-hyperthermia in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy - an Investigator Initiated Study] [NCT05889390]Phase 2/Phase 3120 participants (Anticipated)Interventional2023-02-20Recruiting
A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Osimertinib in Patients With Advanced, Metastatic EGFR-Mutant, Metastatic Non-Small Cell Lung Cancer [NCT04486833]Phase 1/Phase 2158 participants (Anticipated)Interventional2021-09-03Recruiting
A Phase 1b Dose Escalation/Phase 2 Randomized, Non-Comparative, Multiple Center, Open Label Study Of CP 751,871 In Combination With Paclitaxel And Carboplatin And Of Paclitaxel And Carboplatin Alone As First Line Treatment For Advanced Non-Small Cell Lung [NCT00147537]Phase 1/Phase 2282 participants (Actual)Interventional2005-02-28Completed
Phase I/II Study of AMG 531 in Patients With Advanced Malignancy Receiving Treatment With Carboplatin [NCT00147225]Phase 1/Phase 255 participants (Actual)Interventional2005-08-31Completed
A Phase 1 Dose-Finding Study Of The Anti-Angiogenesis Agent, AG-013736, In Combinations Of Paclitaxel/Carboplatin, Weekly Paclitaxel, Docetaxel, Capecitabine, Gemcitabine/Cisplatin and Pemetrexed/Cisplatin In Patients With Advanced Solid Tumors [NCT00454649]Phase 1102 participants (Actual)Interventional2005-12-31Completed
Chemoradiation Combined With Panitumumab Followed by Surgery for Patients With Operable Esophageal Cancer [NCT01077999]Phase 278 participants (Actual)Interventional2010-01-31Completed
Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Optional Postoperative Normothermic Intraperitoneal (IP) Chemotherapy to Treat Primary or Recurrent Carcinoma of Ovarian, Fallopian Tube, Uterine, or Peritoneal Origin [NCT01970722]Phase 140 participants (Anticipated)Interventional2014-05-19Active, not recruiting
Phase II Study of Panitumumab, Nab-paclitaxel, and Carboplatin for Patients With Primary Inflammatory Breast Cancer (IBC) Without HER2 Overexpression [NCT01036087]Phase 247 participants (Actual)Interventional2010-11-30Completed
Image-Guided Hypofractionated Radiotherapy With Stereotactic Boost and Chemotherapy for Inoperable Stage II-III Non-Small Cell Lung Cancer [NCT01345851]29 participants (Actual)Interventional2011-03-23Active, not recruiting
A Phase 1/2, Open-label, Dose-exploration and Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of NTX-301 Monotherapy in Advanced Solid Tumours, and in Combination With Platinum-based Chemotherapy in Advanced Ova [NCT04851834]Phase 1/Phase 212 participants (Actual)Interventional2021-08-25Terminated(stopped due to Study was terminated by IP Holder (collaborator), PinotBio Inc.)
Open-label, Multicenter, Phase I/II Trial to Evaluate Efficacy Safety of the Combination Therapy of Genexol-PM and Carboplatin as a Firstline Treatment in Subjects With Advanced Ovarian Cancer [NCT00886717]Phase 1/Phase 274 participants (Anticipated)Interventional2008-05-31Recruiting
A Phase II First-Line Study of a Combination of Pemetrexed, Carboplatin and Bevacizumab in Advanced Nonsquamous NSCLC Evaluating Efficacy and Tolerability in Elderly Patients (Age ≥ 70 Yrs) With Good Performance Status (PS < 2) [NCT00798603]Phase 265 participants (Actual)Interventional2008-12-31Completed
Phase 2 Study of CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer [NCT00945191]Phase 224 participants (Actual)Interventional2009-10-06Completed
A Phase I/II, Single Center, Proof-of-Concept Study of Birinapant in Combination With Platinum Based Chemotherapy Targeting Recurrent High Grade Serous Ovarian Carcinomas (HGSOC) [NCT02756130]Phase 1/Phase 20 participants (Actual)Interventional2018-08-01Withdrawn(stopped due to funding was not secured)
A Phase 3, Randomised, Double-blind Study to Compare the Efficacy, Safety, PK and Immunogenicity Between SB8 (Proposed Bevacizumab Biosimilar) and Avastin® in Subjects With Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer [NCT02754882]Phase 3763 participants (Actual)Interventional2016-07-05Completed
Pharmacokinetics and Pharmacogenetics of Anticancer Drugs in Infants and Young Children [NCT00897871]60 participants (Anticipated)Observational2007-02-28Recruiting
Development of a Serum Proteomic Classifier for the Prediction of Benefit From Bevacizumab in Combination With Carboplatin and Paclitaxel [NCT00898417]90 participants (Actual)Observational2008-03-14Completed
SCOPE2 - A Randomised Phase II/III Trial to Study Radiotherapy Dose Escalation in Patients With Oesophageal Cancer Treated With Definitive Chemo-radiation With an Embedded Phase II Trial for Patients With a Poor Early Response Using Positron Emission Tomo [NCT02741856]Phase 2/Phase 3584 participants (Anticipated)Interventional2016-11-04Recruiting
A Phase 1b Trial of Adaptive Stereotactic Body Radiotherapy in Combination With Durvalumab (MEDI4736), Platinum, and Etoposide in Extensive Stage Small Cell Lung Cancer [NCT05403723]Phase 150 participants (Anticipated)Interventional2023-02-24Recruiting
A Randomized, Crossover Phase 1 Study to Evaluate the Effects of Pevonedistat on the QTc Interval in Patients With Advanced Solid Tumors [NCT03330106]Phase 168 participants (Actual)Interventional2017-11-15Completed
A Clinical Research of NK Cell Infusion Combined With Chemotherapy in the Treatment of Non-small Cell Lung Cancer [NCT02734524]Phase 2104 participants (Anticipated)Interventional2016-03-31Recruiting
Everolimus (RAD001) in Combination With Intravenous Carboplatin in Taxane- and Anthracycline-pretreated Patients With Progressive Metastatic Breast Cancer [NCT00930475]Phase 1/Phase 254 participants (Anticipated)Interventional2009-02-28Recruiting
Randomized Study Comparing Two Strategies Carboplatin and Etoposide Topotecan in Patients With SCLC on the Second Row With Relapsed at Least Three Months After Initial Response to Chemotherapy With Platinum-etoposide 6 Cycles [NCT02738346]Phase 3164 participants (Anticipated)Interventional2013-07-31Recruiting
Primary Chemoradiation VS. Neoadjuvant Chemotherapy Followed By Surgery As Treatment Strategy For Locally Advanced Vulvar Carcinoma [NCT05905315]Phase 298 participants (Anticipated)Interventional2023-09-01Not yet recruiting
A Phase II Trial Of Carboplatin And Gemcitabine With Exisulind In Patients With Advanced Non-Small Cell Lung Cancer [NCT00041314]Phase 20 participants Interventional2002-10-04Completed
A Phase II Trial OF Chemoradiation For Organ Preservation In Resectable Stage III or IV Squamous Cell Carcinomas Of The Larynx Or Oropharynx [NCT00014118]Phase 20 participants Interventional2001-06-06Completed
A Randomized Phase II Trial of Paclitaxel-Carboplatin or Gemicitabine-Cisplatin in ECOG Performance Status 2 Non-Small Cell Lung Cancer Patients [NCT00006004]Phase 20 participants Interventional2000-08-22Completed
A Phase II Trial of Docetaxel and Carboplatin in Patients With Advanced Squamous Carcinoma of the Esophagus [NCT00003864]Phase 20 participants Interventional1999-09-03Completed
A Phase III Randomized Trial of Either M-VAC or Paclitaxel + Carboplatin as Postoperative Adjuvant Therapy in Patients With Muscle-Invasive Transitional Cell Carcinoma of the Bladder at High-Risk for Relapse [NCT00003701]Phase 3490 participants (Anticipated)Interventional1999-04-02Completed
A Phase III Trial of Induction Paclitaxel and Carboplatin Followed By Standard Radiotherapy (64 Gy/7 Weeks) vs. Hyperfractionated Accelerated Radiotherapy (HART 57.6 Gy/2.5 Weeks) For Patients With Unresectable Stage IIIA and IIIB Non-Small Cell Lung Canc [NCT00003235]Phase 3294 participants (Anticipated)Interventional1998-06-01Completed
A Phase II Trial of Carboplatin Plus Paclitaxel in the Treatment of Locally Recurrent or Metastatic Nasopharyngeal Carcinoma [NCT00003206]Phase 20 participants Interventional1999-10-06Completed
Intravitreal Carboplatin for the Treatment of Participants With Recurrent or Refractory Intraocular Retinoblastoma [NCT02792036]Phase 18 participants (Actual)Interventional2016-11-01Completed
Pilot Study of Induction Therapy Followed by Response-adaptive Treatment and Dynamic Changes in Circulating Tumor DNA in Locoregionally Advanced HPV Negative Head and Neck Squamous Cell Carcinoma [NCT06005324]Phase 136 participants (Anticipated)Interventional2023-12-31Not yet recruiting
A Phase II Randomized Trial Evaluating Neoadjuvant Dose-Dense Doxorubicin/Cyclophosphamide Followed by Paclitaxel/Trastuzumab/Pertuzumab (AC THP) and Docetaxel/Carboplatin/Trastuzumab/Pertuzumab (TCHP) For Early Her2Neu Positive Breast Cancer [NCT03329378]Phase 27 participants (Actual)Interventional2019-01-24Terminated(stopped due to Data Safety Monitoring Board is in agreement with the study findings so far and the stopping rule has been met, which suspends the study treatment arms in March 2021.)
A Double Blind Randomized Trial of Cediranib Versus Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00795340]Phase 3306 participants (Actual)Interventional2009-02-04Completed
Treatment of Intracranial Germinoma With Chemotherapy Prior to Reduced Dose and Volume of Radiotherapy [NCT02782754]Phase 240 participants (Anticipated)Interventional2013-01-31Recruiting
A Phase I Trial Testing TH-302, a Tumor-selective Hypoxia-Activated Cytotoxic Prodrug, in Combination With Preoperative Chemoradiotherapy in Patients With Distal Esophageal and Esophago-gastric Junction Adenocarcinoma [NCT02598687]Phase 10 participants (Actual)Interventional2015-12-31Withdrawn(stopped due to 2 Phase 3 trials didn't meet their primary endpoint, so further development and testing of TH-302 is uncertain)
"A Randomized Non-comparative Open-label Phase 1b/2 Study of Nadunolimab in Combination With Gemcitabine Plus Carboplatin in Patients With Advanced Triple Negative Breast Cancer. TRIFOUR Study" [NCT05181462]Phase 1/Phase 2116 participants (Anticipated)Interventional2022-01-11Recruiting
A Randomized Phase 2 Study of Human Anti-PDGFRα Monoclonal Antibody (IMC-3G3) With Paclitaxel/Carboplatin or Paclitaxel/Carboplatin Alone in Previously Untreated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00918203]Phase 2137 participants (Actual)Interventional2010-01-31Completed
A Bayesian Randomized Trial of Image-Guided Adaptive Conformal Photon vs Proton Therapy, With Concurrent Chemotherapy, for Locally Advanced Non-Small Cell Lung Carcinoma: Treatment Related Pneumonitis and Locoregional Recurrence [NCT00915005]Phase 2275 participants (Actual)Interventional2009-06-30Completed
A Randomized, Open-Label, Controlled, Multicenter Phase III Study of Camrelizumab Combined With Apatinib Mesylate or Camrelizumab Alone Versus Platinum-based Chemotherapy for First-line Treatment in Subjects With PD-L1 Positive Relapsed or Advanced NSCLC [NCT04203485]Phase 3762 participants (Anticipated)Interventional2020-06-15Not yet recruiting
A Single Arm,Open-label, Study of Fruquintinib Combined With Sintilimab and Chemotherapy in Patients With Unresectable or Metastatic Advanced Wild-type Genotype Non-squamous Non-small Cell Lung Cancer [NCT04956146]Phase 246 participants (Anticipated)Interventional2022-02-02Recruiting
Randomized Phase II Study of Durvalumab or Durvalumab Plus Chemotherapy in Kras Mutation Positive and PD-L1 High (≥ 50%) NSCLC Patients [NCT04470674]Phase 20 participants (Actual)Interventional2021-04-06Withdrawn(stopped due to Lack of Accrual)
A Randomized, Placebo-controlled, Double-blind Phase III Study of the Effect of First-line Treatment With Intercalated Tarceva Versus Placebo in Combination With Gemcitabine/Platinum on Progression-free Survival in Patients With Stage IIIB/IV Non-small Ce [NCT00883779]Phase 3451 participants (Actual)Interventional2009-04-30Completed
Immunotherapy With MK-3475 in Surgically Resectable Endometrial Carcinoma [NCT02630823]Phase 110 participants (Actual)Interventional2016-02-05Completed
A Phase II Randomized Study Of Intraductal Carboplatin In Women With Ductal Carcinoma In Situ [NCT00669747]Phase 245 participants (Anticipated)Interventional2008-05-31Recruiting
A Randomized, Open-label, Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Patients With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma [NCT02703272]Phase 372 participants (Actual)Interventional2016-07-01Terminated(stopped due to IDMC recommended that enrolment be stoped, as the EFS hazard ratio and associated p-value crossed the futility boundary specified in protocol (July 2020).)
Randomized, Double-blinded, Placebo Controlled, Multicenter, Phase III Study of Carboplatin Plus Etoposide With or Without SHR-1316 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) [NCT03711305]Phase 3462 participants (Actual)Interventional2018-12-30Active, not recruiting
Phase II Trial of Radiotherapy, Carboplatin/Paclitaxel and Nivolumab for High Risk HPV-Related Oropharynx Cancer [NCT03829722]Phase 226 participants (Actual)Interventional2019-09-05Active, not recruiting
A Randomized, Double-blind, Phase 2 Study of BMS-986315 and Nivolumab in Combination With Chemotherapy Versus Nivolumab in Combination With Chemotherapy as First-line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC) [NCT06094296]Phase 2196 participants (Anticipated)Interventional2023-11-03Not yet recruiting
A Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-DOTA-TATE in Newly Diagnosed Extensive Stage Small Cell Lung Cancer (ES-SCLC) in Combination With Carboplatin, Etoposide and Tislelizumab in Induction and With Tislelizumab in Mainte [NCT05142696]Phase 139 participants (Anticipated)Interventional2022-07-13Recruiting
A Phase IIIb, Single-arm, Multi-center, International Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer (LUMINANCE) [NCT04774380]Phase 3152 participants (Actual)Interventional2021-11-11Active, not recruiting
A Global, Randomised, Phase 3, Open-label Study of REGN2810 (ANTI-PD 1 Antibody) Versus Platinum Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic PD L1+Non-small Cell Lung Cancer [NCT03088540]Phase 3712 participants (Actual)Interventional2017-05-29Active, not recruiting
Genomics-Based Target Therapy for Children With Relapsed or Refractory Malignancy [NCT02638428]Phase 290 participants (Anticipated)Interventional2015-12-31Recruiting
"A Feasibility Trial of Partial Breast Irradiation With Various Concurrent Chemotherapy Regimens (PBIC)" [NCT00681993]35 participants (Actual)Interventional2008-04-30Completed
CCLG Observational Study of the Outcome of Ependymoma in Infants Diagnosed Before Their Third Birthday [NCT00683319]50 participants (Anticipated)Observational2008-04-30Active, not recruiting
Clinical Study of Nab-paclitaxel Plus Carboplatin Versus Nab-paclitaxel Plus Epirubicin in the Neoadjuvant Therapy for Breast Cancer [NCT04138719]Phase 2520 participants (Anticipated)Interventional2019-11-20Recruiting
A Randomized, Double-blind, Controlled, Multicenter Phase III Study of TQB2450 or Placebo Combined With Anlotinib, Etoposide and Carboplatin Versus Etoposide and Carboplatin in Subjects With Extensive Small Cell Lung Cancer [NCT04234607]Phase 3738 participants (Anticipated)Interventional2020-01-31Not yet recruiting
A Pilot Study of Intravenous Topotecan and Vincristine in Combination With Subconjunctival Carboplatin for Patients With a History of Bilateral Retinoblastoma and Refractory/Recurrent Intraocular Disease (IND# 104,942) [NCT00980551]0 participants (Actual)Interventional2010-05-31Withdrawn(stopped due to No enrollment and competing studies)
Comparison of Concomitant Cisplatin Versus Carboplatin and 5-fluorouracil With Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT02778191]413 participants (Actual)Observational2016-02-29Completed
A Randomized, Open-Label Study to Evaluate the Efficacy and Safety of Obatoclax Mesylate in Combination With Carboplatin and Etoposide Compared With Carboplatin and Etoposide Alone in Chemotherapy-Naive Patients With Extensive-Stage Small Cell Lung Cancer [NCT01563601]Phase 30 participants (Actual)Interventional2012-08-31Withdrawn(stopped due to Business Decision)
Phase II Trial of Neoadjuvant Metronomic Chemotherapy in Triple-Negative Breast Cancer [NCT00542191]Phase 230 participants (Actual)Interventional2007-07-31Terminated(stopped due to Enrollment Completed)
Pembrolizumab + Platinum Doublets Without Radiation for Patients With PD-L1 ≥50% Locally Advanced Non-small Cell Lung Cancer: a Multicenter Prospective Single Arm Phase II Study [NCT04153734]Phase 221 participants (Anticipated)Interventional2019-12-01Not yet recruiting
A Global Phase 3, Randomized, Placebo Controlled, Double-Blind Trial of AMG 706 in Combination With Paclitaxel and Carboplatin for Advanced Non-Squamous Non-Small Cell Lung Cancer (Asian Phase 3 Study) [NCT02629848]Phase 3401 participants (Actual)Interventional2012-07-31Terminated(stopped due to Sponsor decision to terminate the study because the study did not meet the primary endpoint.)
An Open-label, Randomized, Phase I/II Trial Investigating the Safety and Efficacy of IO102 in Combination With Pembrolizumab, With or Without Chemotherapy, as First-line Treatment for Patients With Metastatic Non-Small Cell Lung Cancer [NCT03562871]Phase 1/Phase 2109 participants (Actual)Interventional2018-08-22Completed
Efficacy and Safety Study of Imprime PGG® Injection in Combination With Cetuximab and Concomitant Paclitaxel and Carboplatin Therapy in Patients With Previously Untreated Advanced (Stage IIIB or IV) Non-Small Cell Lung Cancer [NCT00874848]Phase 290 participants (Actual)Interventional2009-08-31Completed
A Clinical Experience Trial to Detect the Plasma Paclitaxel Drug Concentration in Chinese Non -Small Cell Lung Cancer (NSCLC) Patients Treated With a Paclitaxel Plus Carboplatin (TC) Regimens, and Explore Individualized Treatment Using Pharmacokinetically [NCT02737709]Phase 251 participants (Actual)Interventional2016-03-31Terminated(stopped due to The study have difficulty in recruiting subjectes)
Randomized, Phase III-b, Multi-centre, Open-label, Parallel Study of Enoxaparin (Low Molecular Weight Heparin) Given Concomitantly With Chemotherapy vs Chemotherapy Alone in Patients With Inoperable Gastric and Gastro-oesophageal Cancer [NCT00718354]Phase 3740 participants (Actual)Interventional2008-07-31Completed
A Phase I/II Study of Methylselenocysteine (MSC) in Combination With Immunochemotherapy (R-ICE) in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL) [NCT00829205]Phase 1/Phase 20 participants (Actual)Interventional2009-01-31Withdrawn
Intra-arterial (Ophthalmic Artery) Chemotherapy for Retinoblastoma [NCT00857519]10 participants (Actual)Interventional2009-01-31Completed
Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination With Radiation for Patients With Unresectable Stage III Non-Small Cell Lung Cancer: A Phase II, Multi-Center Trial [NCT00526890]Phase 216 participants (Actual)Interventional2006-10-31Terminated(stopped due to lack of efficacy)
Open-label, Multicenter, Phase I Trial to Evaluate Efficacy and Safety of the Combination Therapy of Genexol®-PM Plus Carboplatin as a Firstline Treatment in Subjects With Advanced Ovarian Cancer [NCT00877253]Phase 118 participants (Actual)Interventional2008-05-31Completed
Surufatinib Combined With Serplulimab Plus Carboplatin and Etoposide as First-line Treatment for Extensive-stage Small-cell Lung Cancer：a Multicenter, Open-label, Phase I/II Trial [NCT05882630]Phase 1/Phase 239 participants (Anticipated)Interventional2023-06-01Not yet recruiting
Clinical Application of Efficacy Prediction Model Based on Epigenomics Sequencing Technology in Neoadjuvant Immunotherapy for Esophageal Cancer [NCT05880082]Phase 262 participants (Anticipated)Interventional2023-05-31Not yet recruiting
A Pilot Study of Radiation De-Escalation for p16 Negative Oropharyngeal Cancer and p16-Negative or Positive Laryngeal and Hypopharyngeal Cancers [NCT05544136]Phase 236 participants (Anticipated)Interventional2022-09-12Recruiting
An Open-label, Multi-center Phase Ib/III Study Evaluating the Efficacy and Safety of IBI351 in Combination With Sintilimab ± Chemotherapy in Advanced Non-squamous Non-small Cell Lung Cancer Subjects With KRAS G12C Mutation [NCT05504278]Phase 1144 participants (Anticipated)Interventional2022-09-20Recruiting
A Phase I Study of Durvalumab (MEDI4736) Plus Tremelimumab in Combination With Platinum-based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer and Performance Status 2 [NCT03963414]Phase 11 participants (Actual)Interventional2020-09-25Terminated(stopped due to low accrual)
QUILT 2.023: A Phase 3, Open-Label, 3-Cohort Randomized Study of N-803, in Combination With Current Standard of Care VS Standard of Care as First-Line Treatment for Patients With Advanced or Metastatic NSCLC. [NCT03520686]Phase 31,538 participants (Anticipated)Interventional2018-05-18Active, not recruiting
A Phase II Trial of Nivolumab/Nab-paclitaxel/Carboplatin Induction Chemotherapy Followed by Response-stratified Locoregional Therapy for Patients With Locoregionally Advanced HPV-related Oropharyngeal Cancer- the OPTIMA II Trial [NCT03107182]Phase 276 participants (Actual)Interventional2017-06-27Active, not recruiting
A Phase II Study of Intraperitoneal (IP) Plus Intravenous (IV) Chemotherapy Versus IV Carboplatin Plus Paclitaxel in Patients With Epithelial Ovarian Cancer Optimally Debulked at Surgery Following Neoadjuvant Intravenous Chemotherapy [NCT00993655]Phase 2275 participants (Actual)Interventional2010-03-03Completed
Randomized, Multicenter Phase II Study of Pembrolizumab in Combination With Chemotherapy and Chemoradiation in Locally Advanced Esophageal Adenocarcinoma [NCT02998268]Phase 239 participants (Actual)Interventional2017-03-07Active, not recruiting
European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors [NCT02813135]Phase 1/Phase 2460 participants (Anticipated)Interventional2016-08-03Recruiting
A Randomized Phase 3 Study Comparing Pemetrexed-Carboplatin With Docetaxel-Carboplatin as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00520676]Phase 3260 participants (Actual)Interventional2007-10-31Completed
A Phase II Study Assessing the Efficacy of Etoposide Free Chemotherapy Plus Durvalumab (MEDI4736) in First Line Extensive Disease Small Cell Lung Cancer (SCLC) [NCT05856695]Phase 267 participants (Anticipated)Interventional2023-11-17Recruiting
A Phase 3 Randomized, Open-label Clinical Study to Evaluate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Coformulated With Hyaluronidase (MK-3475A) Versus Intravenous Pembrolizumab, Administered With Chemotherapy, in the First-line Treatm [NCT05722015]Phase 3339 participants (Anticipated)Interventional2023-02-14Active, not recruiting
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy and Safety of Multiple Treatment Combinations in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck (Morpheus-Head and Neck Cancer) [NCT05459129]Phase 1/Phase 290 participants (Anticipated)Interventional2023-04-13Recruiting
A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Patients With Previously Untreated, Locally Advanced, Inoperable or Metastatic Triple-Negative Breast Cancer Whose Tumors Do Not Express PD-L1 or in [NCT05382299]Phase 3540 participants (Anticipated)Interventional2022-07-20Recruiting
A Randomized, Open-label, Phase 3 Study of Sacituzumab Govitecan and Pembrolizumab Versus Treatment of Physician's Choice and Pembrolizumab in Patients With Previously Untreated, Locally Advanced Inoperable or Metastatic Triple-Negative Breast Cancer, Who [NCT05382286]Phase 3440 participants (Anticipated)Interventional2022-07-25Recruiting
Open-label Phase 3 Study of MK-7684A (Coformulation of Vibostolimab With Pembrolizumab) in Combination With Concurrent Chemoradiotherapy Followed by MK-7684A Versus Concurrent Chemoradiotherapy Followed by Durvalumab in Participants With Unresectable, Loc [NCT05298423]Phase 3784 participants (Anticipated)Interventional2022-05-03Recruiting
A Multicenter, Open-label, Phase 2 Basket Study of MK-7684A, a Co-formation of Vibostolimab (MK-7684) With Pembrolizumab (MK-3475), With or Without Other Anticancer Therapies in Participants With Selected Solid Tumors [NCT05007106]Phase 2610 participants (Anticipated)Interventional2021-09-16Recruiting
A Phase II, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab, With or Without Platinum-Based Chemotherapy, in Patients With Previously Untreated Locally Advanced Resectable Stage II [NCT04832854]Phase 250 participants (Actual)Interventional2021-04-23Active, not recruiting
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer [NCT04665856]Phase 3123 participants (Actual)Interventional2020-12-22Active, not recruiting
Phase II, Single-Arm Study of Low-Dose Radiotherapy (LDRT) Concurrent Cisplatin/Carboplatin Plus Etoposide With Atezolizumab for Patients With Extensive-Stage Small Cell Lung Cancer [NCT04622228]Phase 256 participants (Actual)Interventional2020-12-16Active, not recruiting
Comparing the Efficacy and Security of Nab-PHP and TCbHP in Neoadjuvant Chemotherapy for HER2 Positive Operable Breast Cancer , A Multicenter, Randomized, Phase III Clinical Trial [NCT04547907]Phase 3686 participants (Anticipated)Interventional2020-09-18Recruiting
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating The Efficacy And Safety Of Multiple Treatment Combinations In Patients With Metastatic Breast Cancer (Morpheus-panBC) [NCT03424005]Phase 1/Phase 2242 participants (Anticipated)Interventional2018-04-02Recruiting
A Phase II, Open-Label, Multi-Arm Study to Determine the Preliminary Efficacy of Novel Combinations of Treatment in Patients With Platinum Refractory Extensive-Stage Small-Cell Lung Cancer [NCT02937818]Phase 272 participants (Actual)Interventional2016-11-28Completed
[NCT02916511]Phase 270 participants (Actual)Interventional2016-09-01Completed
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line MEDI4736 (Durvalumab) Monotherapy and MEDI4736 (Durvalumab) in Combination With Tremelimumab Versus Standard of Care Chemotherapy in Patients With Unresectable Stage [NCT02516241]Phase 31,126 participants (Actual)Interventional2015-11-02Active, not recruiting
A Randomized Multicenter, Double-Blind, Placebo-Controlled Comparison of Chemotherapy Plus Trastuzumab Plus Placebo Versus Chemotherapy Plus Trastuzumab Plus Pertuzumab as Adjuvant Therapy in Patients With Operable HER2-Positive Primary Breast Cancer [NCT01358877]Phase 34,804 participants (Actual)Interventional2011-11-08Active, not recruiting
Phase II Trial of Single Agent ABT-888 With Post-Progression Therapy of ABT-888 in Combination With Carboplatin in Patients With Stage IV BRCA-Associated Breast Cancer [NCT01149083]Phase 271 participants (Anticipated)Interventional2010-06-30Active, not recruiting
Effectiveness of Atezolizumab in Large Cell Neuroendocrine Carcinoma of the Lung and the Value of miR21 and miR-375 as Biomarkers [NCT06049966]Phase 122 participants (Actual)Interventional2018-03-01Completed
A Phase 3, Open-Label, Randomized, Multi-Center Study of DZD9008 Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon [NCT05668988]Phase 3320 participants (Anticipated)Interventional2022-12-13Recruiting
Phase I/II Study of BLU-451 in Advanced Cancers With EGFR Exon 20 Insertion Mutations [NCT05241873]Phase 1/Phase 2332 participants (Anticipated)Interventional2022-03-04Recruiting
An Open-label, Randomized, Multicenter, Phase 3 Study to Assess the Efficacy and Safety of Trastuzumab Deruxtecan as First-line Treatment of Unresectable, Locally Advanced, or Metastatic NSCLC Harboring HER2 Exon 19 or 20 Mutations (DESTINY-Lung04) [NCT05048797]Phase 3264 participants (Anticipated)Interventional2021-10-28Recruiting
Assessment of Safety and Feasibility of Exablate Blood-Brain Barrier Disruption (BBBD) With Microbubbles for the Treatment of Recurrent Glioblastoma (rGBM) in Subjects Undergoing Carboplatin Monotherapy [NCT04440358]Phase 1/Phase 213 participants (Actual)Interventional2020-10-13Active, not recruiting
Assessment of Safety and Feasibility of Exablate Type 2 for Blood-Brain Barrier Disruption (BBBD) With Microbubble Resonators for the Treatment of Recurrent Glioblastoma (rGBM) in Subjects Undergoing Carboplatin Monotherapy [NCT04417088]Phase 1/Phase 230 participants (Anticipated)Interventional2020-11-06Active, not recruiting
A Phase 1b/2 Open-Label Trial of Tisotumab Vedotin (HuMax®-TF-ADC) Monotherapy and in Combination With Other Agents in Subjects With Recurrent or Stage IVB Cervical Cancer [NCT03786081]Phase 1/Phase 2214 participants (Actual)Interventional2019-02-27Active, not recruiting
A Phase I/Ib Trial of Pirfenidone Combined With Standard First-Line Chemotherapy in Advanced-Stage Lung NSCLC [NCT03177291]Phase 148 participants (Actual)Interventional2017-09-26Active, not recruiting
Carboplatin and Paclitaxel Plus ASA404 as First Line Chemotherapy for Extensive-Stage Small-Cell Lung Cancer (ES-SCLC): A Phase II Trial [NCT01057342]Phase 217 participants (Actual)Interventional2010-01-31Completed
A Phase II Trial of Carboplatin (CBDCA) and ABI-007(ABX) in Patients With Unresectable Stage IV Melanoma [NCT00404235]Phase 276 participants (Actual)Interventional2006-10-31Completed
A Phase II Study of Radiation Therapy, Paclitaxel Poliglumex, and Carboplatin in Stage III Non-Small Cell Lung Cancer [NCT00352690]Phase 210 participants (Actual)Interventional2006-04-30Terminated(stopped due to Safety of patients)
Open-Labeled, Randomized Multi-Center Phase II Study Evaluating the Efficacy and Safety of Paclitaxel/ Carboplatin With and Without Cetuximab as First-Line Treatment of Adeno- and Undifferentiated Carcinoma of Unknown Primary (CUP) [NCT00894569]Phase 2150 participants (Anticipated)Interventional2009-07-31Not yet recruiting
A Phase 1b Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of BMS-833923 (XL139) in Combination With Carboplatin and Etoposide Followed by BMS-833923 Alone in Subjects With Extensive-Stage Small Cell Lung Cancer [NCT00927875]Phase 15 participants (Actual)Interventional2010-02-28Completed
A Phase III, Multicenter, Randomized, Study of Atezolizumab Versus Placebo Administered in Combination With Paclitaxel, Carboplatin, and Bevacizumab to Patients With Newly-Diagnosed Stage III or Stage IV Ovarian, Fallopian Tube, or Primary Peritoneal Canc [NCT03038100]Phase 31,301 participants (Actual)Interventional2017-03-08Completed
Safety and Efficacy of Anlotinib Hydrochloride Combined With Pemetrexed Plus Cisplatin/Carboplatin (AP) as First Line Treatment for Stage IIIB/IIIC/IV Non-squamous Non-small-cell Lung Cancer [NCT04012619]Phase 18 participants (Actual)Interventional2019-04-30Completed
A Phase 1 Study of Veliparib in Combination With Carboplatin and Gemcitabine in Subjects With Advanced Solid Tumors [NCT01063816]Phase 179 participants (Actual)Interventional2010-01-31Completed
A Phase II Study of Chemoimmunotherapy for Patients With Potentially Platinum Sensitive Müllerian (Epithelial Ovarian, Peritoneal, or Fallopian Tube) Carcinomas [NCT00501644]Phase 259 participants (Actual)Interventional2003-01-31Completed
Phase II Trial of Cetuximab in Combination With Chemotherapy (Carboplatin and Navelbine) for Patients With Platinum-resistant Head and Neck Cancer [NCT01020864]Phase 20 participants (Actual)Interventional2010-01-31Withdrawn
A Phase 1b, Parallel Arm, Multicenter, Open-Label Study of the Safety and Pharmacokinetics of AGS-8M4 Given in Combination With Two Different Chemotherapy Regimens in Women With Platinum Resistant or Platinum Sensitive Ovarian Cancer [NCT01016054]Phase 14 participants (Actual)Interventional2009-10-31Terminated(stopped due to Trial was terminated to allow sponsors to evaluate the future development of the drug program)
Phase 2, Randomized, Double Blind, Placebo-Controlled Dose and Schedule Finding Trial to Evaluate the Safety and Efficacy of AMG 531 For Treatment of Chemotherapy-Induced Thrombocytopenia in Subjects With Advanced Non-Small Cell Lung Cancer Already Receiv [NCT00413283]Phase 263 participants (Actual)Interventional2006-12-31Completed
A Randomized Phase 2 Study of Pemetrexed in Combination With Cisplatin or Carboplatin in the First Line Therapy of Advanced NSCLC [NCT00402051]Phase 2133 participants (Actual)Interventional2006-11-30Completed
A Randomized Phase II Trial of Pemetrexed/Gemcitabine/Bevacizumab or Pemetrexed/Carboplatin/Bevacizumab in the First-Line Treatment of Elderly Patients With Advanced Non-Small Cell Lung Cancer [NCT00456261]Phase 2110 participants (Actual)Interventional2007-03-31Completed
Phase II Concurrent Proton and Chemotherapy in Locally Advanced Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC) [NCT00495170]Phase 284 participants (Actual)Interventional2006-04-14Completed
An Open-label Phase II Study of Weekly Intravenous Hycamtin and Carboplatin as First-line Treatment of Chemonaive Subjects With Extensive Disease Small Cell Lung Cancer [NCT00316186]Phase 233 participants (Actual)Interventional2005-06-30Completed
Docetaxel, Carboplatin, Trastuzumab and Bevacizumab (TCH+B) For Early-Stage HER-2/Neu(+) Breast Cancer and Bone Marrow Micrometastases [NCT00949247]Early Phase 120 participants (Actual)Interventional2009-12-31Completed
Phase II Clinical Trial of Patients With High-Grade Glioma Treated With Intra-Arterial Carboplatin-Based Chemotherapy, Randomized to Treatment With or Without Delayed Intravenous Sodium Thiosulfate as a Potential Chemoprotectant Against Severe Thrombocyto [NCT00075387]Phase 248 participants (Actual)Interventional2003-03-07Active, not recruiting
A Randomized Phase II Study of Two Chemotherapy Regimens, Pemetrexed-Carboplatin, and Gemcitabine-Vinorelbine, in Anthracycline and Taxanes Pretreated Advanced Breast Cancer Patients [NCT00325234]Phase 2135 participants (Actual)Interventional2006-06-30Completed
A Randomized Phase 2 Study of Pemetrexed in Combination With Cisplatin or Carboplatin as Adjuvant Chemotherapy in Patients With Completely Resected Stage Ib or II Non-Small Cell Lung Cancer [NCT00269152]Phase 2122 participants (Actual)Interventional2005-12-31Completed
Phase I/II Trial of Induction Carboplatin/Paclitaxel With Bevacizumab Followed by Concurrent Thoracic Conformal Radiation Therapy With Carboplatin/Paclitaxel, Bevacizumab and Erlotinib in Stage IIIA/B Non-Small Cell Lung Cancer [NCT00280150]Phase 1/Phase 246 participants (Actual)Interventional2006-01-31Completed
A Multi-Institutional Double-Blind Phase II Study Evaluating Response and Surrogate Biomarkers to Carboplatin and Nab-Paclitaxel (CP) With or Without Vorinostat as Preoperative Chemotherapy in HER2-negative Primary Operable Breast Cancer [NCT00616967]Phase 268 participants (Actual)Interventional2008-05-31Active, not recruiting
A Phase I Study of Intravenous Carboplatin/Paclitaxel or Intravenous and Intraperitoneal Paclitaxel/Cisplatin in Combination With Continuous or Intermittent /CTEP-Supplied Agent ABT-888 (NSC #737664) and CTEP-Supplied Agent Bevacizumab (NSC #704865) in Ne [NCT00989651]Phase 1431 participants (Actual)Interventional2009-10-28Completed
National Wilms Tumor Study-5 -- Treatment of Relapsed Patients, A National Wilms Tumor Study Group Phase III Study [NCT00002610]Phase 3203 participants (Actual)Interventional1996-01-31Completed
An Observational Phase II Trial of Targeted Next Generation Sequencing Analysis for the Efficacy of Trastuzumab Neoadjuvant Chemotherapy in Patients With HER2 Positive Breast Cancer [NCT03728829]100 participants (Anticipated)Observational2021-07-31Recruiting
Phase II Trial of Vaginal Cuff Brachytherapy Followed by Adjuvant Chemotherapy With Carboplatin and Dose Dense Paclitaxel in Patients With High-Risk Endometrial Cancer [NCT03189446]Phase 239 participants (Actual)Interventional2017-10-02Active, not recruiting
A Randomised, Multicentre, Double-blind, Placebo-controlled, Phase III Study of First-line Carboplatin and Paclitaxel in Combination With Durvalumab, Followed by Maintenance Durvalumab With or Without Olaparib in Patients With Newly Diagnosed Advanced or [NCT04269200]Phase 3805 participants (Actual)Interventional2020-05-05Active, not recruiting
A First-in-Human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety and Anti-tumor Activity of GEN1042 in Subjects With Malignant Solid Tumors [NCT04083599]Phase 1/Phase 21,287 participants (Anticipated)Interventional2019-09-17Recruiting
A Phase 3, Multi-center, Randomized, Double-Blind, Placebo-Controlled Study of Either Cisplatin or Carboplatin +Gemcitabine + Tislelizumab Compared With Either Cisplatin or Carboplatin + Gemcitabine + Placebo as First-line Treatment for Patients With Loca [NCT03967977]Phase 3420 participants (Anticipated)Interventional2019-05-29Recruiting
Phase II Trial of Weekly Docetaxel and Four Weekly Carboplatin Combination in the First-line Treatment of Advanced Non-small Cell Lung Cancer [NCT00826852]Phase 249 participants (Actual)Interventional2003-10-31Completed
A Phase III, Randomized, Multi-Center, Open-Label, Comparative Global Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Patients With Metastatic Non Sma [NCT03164616]Phase 31,186 participants (Actual)Interventional2017-06-01Active, not recruiting
Phase 1 Dose Escalation and Expansion Cohort of Carboplatin and Gemcitabine With or Without M6620 (VX-970) in First or Second Recurrence Platinum-Sensitive Epithelial Ovarian, Peritoneal, and Fallopian Tube Cancer [NCT02627443]Phase 131 participants (Anticipated)Interventional2017-05-16Active, not recruiting
Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel Vs. Sandwich Therapy of Carboplatin and Paclitaxel Followed by Tumor Volume Directed Irradiation Then Further Carboplatin and Paclitaxel [NCT02501954]Phase 348 participants (Actual)Interventional2015-03-31Completed
Phase II Trial Evaluating Efficacy of a Strategy Employing Combination Gemcitabine and Carboplatin Chemotherapy Followed by EBV-Specific Cytotoxic T-Lymphocytes in Patients With Metastatic or Locally Recurrent EBV-Positive Nasopharyngeal Carcinoma [NCT00690872]Phase 235 participants (Anticipated)Interventional2008-07-31Recruiting
Etoposide-Carboplatin (EC) Versus EC Plus Endostar in Patients With Extensive Disease Small Cell Lung Cancer (ED-SCLC): Randomized, Open Label, Placebo-controlled, Multicentre Study [NCT00912392]Phase 2138 participants (Actual)Interventional2009-05-31Completed
Combining Afatinib and Concurrent Chemotherapy, Followed by Osimertinib and Concurrent Chemotherapy, in Untreated EGFR Positive NSCLC Tumors [NCT05298176]Phase 221 participants (Anticipated)Interventional2022-01-04Recruiting
Randomized Phase 2 Trial Of AG013736 Or Bevacizumab In Combination With Paclitaxel And Carboplatin As First Line Treatment For Patients With Advanced Non Small Cell Lung Cancer [NCT00600821]Phase 2118 participants (Actual)Interventional2008-04-30Completed
A Phase II Study of Cetuximab, Carboplatin and Radiotherapy for Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT00704639]Phase 1/Phase 260 participants (Actual)Interventional2008-04-30Completed
A Dose Seeking Trial of Topotecan Combined With High-Dose Cyclophosphamide and Carboplatin With Peripheral Blood Stem Cell Transplant for the Treatment of Relapsed Ovarian Cancer and Primary Peritoneal Cancer [NCT00652691]Phase 148 participants (Anticipated)Interventional1998-08-31Completed
A Phase I Dose Escalation Study of MK-2206 in Combination With Standard Doses of Selected Chemotherapies or Targeted Agents in Patients With Locally Advanced or Metastatic Solid Tumors [NCT00848718]Phase 177 participants (Actual)Interventional2009-03-17Completed
Bevacizumab and Carboplatin for Patients With Platin Resistant Epithelial Ovarian Cancer. A Phase II Study. [NCT00744718]Phase 273 participants (Actual)Interventional2008-08-31Completed
Additional Chemotherapy for EGFRm Patients With the Continued Presence of Plasma ctDNA EGFRm at Week 3 After Start of Osimertinib 1st-line Treatment (PACE-LUNG) [NCT05281406]Phase 250 participants (Anticipated)Interventional2021-11-12Recruiting
A Randomized, Double-Blind, Phase III Study of Platinum+Pemetrexed Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-189) [NCT03950674]Phase 340 participants (Actual)Interventional2016-02-22Completed
A Randomized, Double-Blind, Phase III Study of Platinum+Pemetrexed Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Non-squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-189) [NCT02578680]Phase 3616 participants (Actual)Interventional2016-01-15Completed
Randomized Phase II Evaluation of Carboplatin/Paclitaxel With and Without Trastuzumab (Herceptin) in HER2/Neu+ Patients With Advance/Recurrent Uterine Serous Papillary Carcinoma [NCT01367002]Phase 261 participants (Actual)Interventional2011-06-30Completed
Efficacy and Safety of Platinum-based Chemotherapy + Bevacizumab + Durvalumab, and Salvage SBRT for IV Non-Small Cell Lung Cancer Patients With EGFR Mutations After Failure of First Line Osimertinib：A Multicenter, Prospective, Phase II Clinical Study [NCT04517526]Phase 260 participants (Anticipated)Interventional2020-11-01Not yet recruiting
A Phase I Open Label Trial of Continuous Dosing With BIBW 2992 Combined With Paclitaxel and BIBW 2992 Combined With Paclitaxel and Bevacizumab, BIBW 2992 Combined With Carboplatin and BIBW 2992 Combined With Paclitaxel and Carboplatin in Patients With Adv [NCT00809133]Phase 183 participants (Actual)Interventional2007-05-31Completed
A Phase II Study of Docetaxel Plus Carboplatin in Chemonaive Hormone-Refractory Prostate Cancer (HRPC) Patients [NCT00675545]Phase 22 participants (Actual)Interventional2007-05-31Completed
Evaluation of Safety and Efficacy of Serplulimab Plus Chemotherapy in Patients With Histological Transformation From EGFR-mutated NSCLC to SCLC After Treatment: a Single-arm, Multicenter, Open-label Phase II Study [NCT05957510]Phase 236 participants (Anticipated)Interventional2023-07-10Recruiting
AdvanTIG-211: A Randomized, Double-blind, Placebo-controlled, Phase II Study Evaluating the Efficacy and Safety of Ociperlimab (WCD118) Combined With Tislelizumab (VDT482) Plus Chemotherapy Versus Placebo Combined With Pembrolizumab Plus Chemotherapy as F [NCT05809895]Phase 20 participants (Actual)Interventional2023-09-15Withdrawn(stopped due to Business decision, not driven by safety concerns; no new safety signals have been observed in the ociperlimab program.)
AdvanTIG-306: A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Ociperlimab (WCD118/BGB-A1217) Combined With Tislelizumab (VDT482/BGB-A317) Plus Platinum-based Doublet Chemotherapy Versus Placebo Combine [NCT05791097]Phase 30 participants (Actual)Interventional2023-07-28Withdrawn(stopped due to Business decision, not driven by safety concerns; no new safety signals have been observed in the ociperlimab program.)
Evaluating the Efficacy and Safety of TQB2450 Injection Combined With Chemotherapy ± Anlotinib Hydrochloride Capsules for First-line Treatment of Patient With Advanced Endometrial Cancer or Sarcoma of Uterus: a Multi-center, Open-label, Randomized Control [NCT05481645]Phase 279 participants (Anticipated)Interventional2022-08-22Recruiting
Clinical Study of Modified Carboplatin/Vincristine Chemotherapy Regimen for Visual Function Protection in Children With Optic Pathway Gliomas [NCT05278715]Phase 275 participants (Anticipated)Interventional2022-04-13Recruiting
A Phase IIIB, Single Arm, Multicenter Study of Atezolizumab (Tecentriq) in Combination With Carboplatin Plus Etoposide to Investigate Safety and Efficacy in Patients With Untreated Extensive-Stage Small Cell Lung Cancer - MAURIS [NCT04028050]Phase 3155 participants (Actual)Interventional2019-08-12Completed
A Randomized Phase 2 Study of Ixabepilone Plus Carboplatin and Paclitaxel Plus Carboplatin in Patients With Advanced Non-small Cell Lung Cancer [NCT00723957]Phase 2260 participants (Actual)Interventional2008-12-31Completed
A Multicenter, Open-Label, Randomized, Phase II Trial of Docetaxel, Carboplatin and Bevacizumab as First-Line Treatment, Followed by Bevacizumab Plus Pemetrexed Versus Pemetrexed Alone as Second-Line Treatment of Stage IIIB or IV Non-Small Cell Lung Cance [NCT00766246]Phase 2125 participants (Actual)Interventional2008-10-31Terminated(stopped due to Withdrawal of funding support)
A Phase I/II Non-Comparative Study of Paclitaxel Plus Carboplatin in Combination With Vorinostat in Patient With Advanced, Recurrent, Epithelial Ovarian Cancer [NCT00772798]Phase 270 participants (Anticipated)Interventional2007-06-30Recruiting
Phase II Trial of Intrahepatic Artery Chemotherapy With Nexavar in Hepatocellular Carcinoma Patients [NCT00875615]Phase 211 participants (Actual)Interventional2008-12-31Completed
Weekly Paclitaxel-carboplatin Plus Bevacizumab as First Line Therapy for Patients With Triple Negative (ER-,PR-,HER2-) Metastatic Breast Cancer. A Multicenter Phase I-II Study [NCT00691379]Phase 1/Phase 246 participants (Actual)Interventional2008-04-30Completed
An Open-label Randomized Phase II Trial of Belinostat (PXD101) in Combination With Carboplatin and Paclitaxel (BelCaP) Compared to Carboplatin and Paclitaxel in Patients With Previously Untreated Carcinoma of Unknown Primary [NCT00873119]Phase 289 participants (Actual)Interventional2009-02-28Completed
A Phase 2, Open-label Study of IMC-1121B in Combination With Paclitaxel and Carboplatin as First-line Therapy in Patients With Stage IIIB/IV Non-small Cell Lung Cancer [NCT00735696]Phase 241 participants (Actual)Interventional2009-01-31Completed
A Randomized, Parallel, 3-arm Study to Characterize the Effect of Ipilimumab + Chemotherapy in Patients With Untreated Advanced Melanoma [NCT00796991]Phase 172 participants (Actual)Interventional2009-02-28Completed
Treatment of Triple-negative Breast Cancer With Albumin-bound Paclitaxel as Neoadjuvant Therapy: a Prospective Randomized Controlled Clinical Trial [NCT04137653]Phase 31,498 participants (Anticipated)Interventional2021-07-19Recruiting
Evaluation of Benefit and Side Effects of 131I-MIBG in Combination With Myeloablative Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation for the Treatment of High-risk Neuroblastoma [NCT00798148]Phase 1/Phase 210 participants (Anticipated)Interventional2008-09-30Recruiting
A Randomized,Controlled,Open-label,Prospective,Single-center Study to Investigate the Neoadjuvant Therapy of SHR-1210 in Combination With Carboplatin and Paclitaxel-albumin in Combination With Carboplatin and Paclitaxel in Resectable NSCLC [NCT04108013]Phase 238 participants (Anticipated)Interventional2019-10-08Not yet recruiting
Adoptive T Cell Therapy in Patients With Recurrent Ovarian Cancer [NCT04072263]Phase 1/Phase 212 participants (Anticipated)Interventional2018-08-01Recruiting
Phase I Study of Carboplatin, Paclitaxel, Bevacizumab and Vorinostat for Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00702572]Phase 125 participants (Actual)Interventional2008-04-30Terminated(stopped due to Low Enrollment)
Optimized Intensity Modulated Irradiation for Head and Neck Cancer [NCT00580983]90 participants (Actual)Interventional2003-08-31Completed
Paclitaxel Poliglumex (CT-2103)/Carboplatin vs Paclitaxel/Carboplatin for the Treatment of Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer (NSCLC) in Women With Estradiol >30 pg/mL [NCT00551733]Phase 3450 participants (Anticipated)Interventional2007-08-31Terminated
Paclitaxel Plus Carboplatin (TC) Versus TC Plus Endostar in Patients With Advanced Non-small Cell Lung Cancer(NSCLC): a Randomized, Double-blind, Placebo-controlled, Multicentre Study [NCT00708812]Phase 2126 participants (Actual)Interventional2007-07-31Completed
Anlotinib Plus Etoposide and Carboplatin as First-line Treatment for Extensive-stage Small Cell Lung Cancer: A Single Arm Phase II Trial [NCT04684017]Phase 229 participants (Anticipated)Interventional2019-05-01Recruiting
Dose Escalation of Temozolomide in Combination With Thiotepa and Carboplatin With Autologous Stem Cell Rescue in Patients With Malignant Brain Tumors With Minimal Residual Disease [NCT00025558]Phase 10 participants Interventional2000-10-31Completed
Phase 2 Randomized Study of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-Naïve Subjects With Metastatic Non-Small Cell Lung Cancer [NCT00806286]Phase 2111 participants (Actual)Interventional2008-12-31Completed
Phase III Study of Monotherapy by Gemcitabine or Vinorelbine Comparing to Doublet by Carboplatin and Paclitaxel Among Elderly Patients With Stage IIIB/IV NSCLC (Obligatory Second-line by Erlotinib) [NCT00298415]Phase 3451 participants (Actual)Interventional2006-03-31Completed
Randomized Phase III Trial of the Need for Adjuvant Chemotherapy in Stage I Epithelial Ovarian Cancer After Comprehensive Staging Surgery [NCT04063527]Phase 3360 participants (Anticipated)Interventional2012-07-20Recruiting
An Open Label Study to Assess the Effect of Avastin (Bevacizumab) Combined With First Line Paclitaxel-carboplatin or Second Line Tarceva (Erlotinib) on Progression-free Survival in Non-squamous Non-small Cell Lung Cancer Patients With Asymptomatic Untreat [NCT00800202]Phase 291 participants (Actual)Interventional2009-04-30Completed
Stereotactic Radiosurgery and Systemic Dose Chemotherapy for Locally Advanced Lung Cancer (Protocol Number GK001) [NCT02568033]Early Phase 122 participants (Anticipated)Interventional2013-10-31Recruiting
Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma [NCT00588666]Phase 251 participants (Actual)Interventional2006-05-31Completed
Modulating the Expression of Oncoproteins of Papillomavirus (HPV) to Increase Radiosensitivity: a Phase I Study of Antiviral Agent Cidofovir and Chemoradiotherapy Therapy in Cervical Cancers [NCT00811408]Phase 124 participants (Anticipated)Interventional2008-04-30Recruiting
Randomized Phase III Trial of Topotecan and Cisplatin Versus Etoposide and Carboplatin in the Treatment of Patients With Previously Untreated Small Cell Lung Cancer and Extensive Disease [NCT00812266]Phase 3281 participants (Actual)Interventional2006-01-31Terminated(stopped due to Slow accrual)
A Phase II Single Arm Study of Carboplatin and DOXIL (PLD) Plus Bevacizumab in Patients With Platinum Sensitive Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancers [NCT00698451]Phase 254 participants (Actual)Interventional2008-08-31Completed
A Phase II Study of Platinum-doublet Chemotherapy in Combination With Nivolumab as First-line Treatment in Subjects With Unresectable, Locally Advanced or Metastatic G3 Neuroendocrine Neoplasms (NENs) of the Gastroenteropancreatic (GEP) Tract or of Unknow [NCT03980925]Phase 238 participants (Anticipated)Interventional2019-10-11Active, not recruiting
Randomized Phase II Study of Combination Chemotherapy With Sildenafil Plus Carboplatin and Weekly Paclitaxel in Patients With Previously Untreated Advanced Non-small Cell Lung Cancer [NCT00752115]Phase 2/Phase 3120 participants (Anticipated)Interventional2007-02-28Completed
A Cancer Research UK Randomised, Multicentre, Phase II Trial of the DNAhypomethylating Agent, 5-Aza-2'-Deoxycytidine (Decitabine) Given Intravenously in Combination With Carboplatin, Versus Carboplatin Alone Given 4 Weekly in Patients With Progressive, Ad [NCT00748527]Phase 2134 participants (Anticipated)Interventional2007-07-31Terminated(stopped due to "The study was withdrawn due to certain adverse events [hypersensitivity].")
A Randomized Phase II Study Evaluating Vandetanib (ZD6474) in Combination With Docetaxel and Carboplatin Followed by Placebo or Maintenance Therapy With Vandetanib in Patients With IIIb, IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) [NCT00687297]Phase 2162 participants (Actual)Interventional2008-04-30Completed
A Randomized, Double-Blind, International Multi-Centre, Phase III Clinical Study to Evaluate Efficacy and Safety of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) in Combination With Chemotherapy Versus Placebo in Combination With C [NCT04301739]Phase 3522 participants (Anticipated)Interventional2020-04-17Not yet recruiting
Paclitaxel, Carboplatin Plus Bevacizumab in Pretreated, Advanced or Metastatic Non Small Cell Lung Cancer [NCT00753909]Phase 250 participants (Actual)Interventional2008-11-30Completed
A Phase II Clinical Trial of Weekly Paclitaxel and Carboplatin in Combination With Panitumumab in Metastatic Breast Cancer Patients With Triple Negative Disease [NCT01009983]Phase 214 participants (Actual)Interventional2010-03-31Terminated(stopped due to Slow accrual)
Phase II Trial of Carboplatin, Paclitaxel, and Temozolomide for Patients With Metastatic Melanoma [NCT01009515]Phase 219 participants (Actual)Interventional2009-08-31Terminated(stopped due to Low accrual; target accrual not met)
A Phase II Study of Alimta and Carboplatin in the Treatment of Patients With Locally Advanced or Metastatic Breast Cancer [NCT00072865]Phase 250 participants Interventional2003-06-30Completed
A Phase I Investigator-Initiated Study of Selinexor (KPT-330) Plus RICE in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas [NCT02471911]Phase 122 participants (Actual)Interventional2015-12-11Completed
A Randomized Phase II Trial of Vandetanib (ZD6474) in Combination With Carboplatin Versus Carboplatin Alone Followed by Vandetanib Alone in Adults With Recurrent High-Grade Gliomas [NCT00995007]Phase 2112 participants (Actual)Interventional2009-09-30Completed
Phase II, Open-Label, Study of CAELYX and Carboplatin Intermediate Platinum-Sensitive (6-12 Months Treatment-free Interval) Relapsed Epithelial Ovarian Cancer. [NCT00780039]Phase 258 participants (Actual)Interventional2003-10-01Completed
A Phase II Evaluation of Temsirolimus (CCI-779) (NCI Supplied Agent: NSC# 683864,) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus Consolidation as First-Line Therapy in the Treatment of Clear Cell Carcinoma of the Ovary [NCT01196429]Phase 290 participants (Actual)Interventional2010-08-31Completed
A Multicenter, Double Blind, Randomized, Controlled Study of M7824 With Concurrent Chemoradiation Followed by M7824 Versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants With Unresectable Stage III Non-small Cell Lung Cancer [NCT03840902]Phase 2168 participants (Actual)Interventional2019-04-16Terminated(stopped due to Based on recommendations by an external IDMC, Sponsor decided to discontinue this clinical study due to a low likelihood of achieving superiority in the efficacy endpoints versus standard of care.)
Intensity-modulated Radiation Therapy Combined With Cisplatin-based or Carboplatin-based Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma：: A Phase 3 Trial [NCT03919552]Phase 3482 participants (Anticipated)Interventional2018-01-31Recruiting
A Phase I/IB Study of Ipatasertib in Combination With Carboplatin, Carboplatin/Paclitaxel, or Capecitabine/Atezolizumab in Patients With Metastatic Triple Negative Breast Cancer [NCT03853707]Phase 1/Phase 228 participants (Actual)Interventional2019-03-04Active, not recruiting
CADENCE: Carboplatin and Docetaxel in Neoadjuvant Treatment of ER-Negative, HER2-Negative Breast Cancer: A Co-Clinical Trial With Genoproteomic Discovery [NCT02547987]Phase 225 participants (Actual)Interventional2015-11-01Active, not recruiting
Phase II Trial of Neoadjuvant Chemotherapy With Carboplatin and NAB-Paclitaxel in Patients With Locally Advanced and Inflammatory Triple Negative Breast Cancer [NCT01525966]Phase 267 participants (Actual)Interventional2012-02-15Active, not recruiting
Phase II Trial Of Paclitaxel Plus Carboplatin In Patients With Metastatic Or Locally Advanced Collecting Duct Renal Cell Cancer [NCT00077129]Phase 222 participants (Anticipated)Interventional2006-06-01Completed
Randomized Double-Blind Placebo Controlled Phase II Trial Evaluating Erlotinib in Non-Smoking Patients With (Bevacizumab-Eligible and Ineligible) Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00976677]Phase 210 participants (Actual)Interventional2010-01-31Terminated
A Phase 1/1b Study of Pevonedistat in Combination With Select Standard of Care Agents in Patients With Higher-Risk Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Acute Myelogenous Leukemia, or Advanced Solid Tumors With Severe Renal Impairmen [NCT03814005]Phase 117 participants (Actual)Interventional2019-07-10Completed
High-dose Chemotherapy With Autologous Hematopoietic Stem Cell Transplantation as Adjuvant Treatment for Triple Negative Breast Cancer Patients Without Complete Pathological Response to Neoadjuvant Chemotherapy [NCT02670109]Phase 220 participants (Anticipated)Interventional2018-02-01Recruiting
Effect of Neoadjuvant Platinum-based Chemoradiation Therapy for Locally Advanced Triple Negative Breast Cancer: Clinical Outcome and Correlation to Biological Parameters [NCT01167192]Phase 210 participants (Actual)Interventional2011-02-28Terminated
A Multicenter, Randomized Phase II Trial of Vinflunine/Gemcitabine vs Carboplatin/Gemcitabine as First Line Treatment in Patients With Metastatic Urothelial Carcinoma Unfit for Cisplatin Based Chemotherapy Due to Impaired Renal Function. [NCT02665039]Phase 262 participants (Actual)Interventional2014-04-30Completed
A Multicenter Phase Ib Trial to Measure [18F]-Fluorodeoxyglucose Uptake by Positron Emission Tomography in Stage IIIB and IV Non-Small Cell Lung Cancer Before and After Chemotherapy With Gemcitabine and Cisplatin or Carboplatin [NCT00599755]Phase 168 participants (Actual)Interventional2009-01-01Completed
Phase I/II Study of Bortezomib (PS-341) in Combination With Carboplatin and Docetaxel for Patients With Advanced Non-Small Cell Lung Cancer [NCT00714246]Phase 16 participants (Actual)Interventional2008-10-31Terminated(stopped due to Low accrual)
Multicenter Study of Safety and Efficacy of PET-adapted Treatment With Nivolumab at the Fixed Dose 40 mg, Ifosfamide, Carboplatin, Etoposide (NICE-40) in Patients With Relapsed/Refractory Hodgkin Lymphoma [NCT04981899]Phase 1/Phase 230 participants (Anticipated)Interventional2021-03-01Recruiting
Phase Ib Trial of Pembrolizumab (MK-3475) With Platinum-Based Chemotherapy in Small Cell/Neuroendocrine Cancers of Urothelium and Prostate [NCT03582475]Phase 115 participants (Actual)Interventional2018-12-20Completed
An Open-label, Multicenter, Phase 2 Study of Sacituzumab Govitecan Combinations in First-line Treatment of Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer (NSCLC) Without Actionable Genomic Alterations [NCT05186974]Phase 2193 participants (Actual)Interventional2022-05-30Active, not recruiting
A Trial of Intensive Multi-Modality Therapy for Extra-Ocular Retinoblastoma [NCT00554788]Phase 360 participants (Actual)Interventional2008-02-04Active, not recruiting
A Phase II Randomized Trial of Paclitaxel, Carboplatin, Bevacizumab With or Without IMC-A12 in Patients With Advanced Non-squamous, Non-small Cell Lung Cancer [NCT00955305]Phase 2175 participants (Actual)Interventional2010-03-31Terminated(stopped due to The study was closed to accrual due to the end of the clinical development program with cixutumumab.)
A Randomized Phase III Study of Standard Treatment +/- Enoxaparin in Small Cell Lung Cancer [NCT00717938]Phase 3390 participants (Actual)Interventional2008-06-30Completed
A Phase III, Two-Arm, Parallel, Randomized, Multi-Center, Open-Label, Global Study to Determine the Efficacy of Volrustomig (MEDI5752) Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy for First-Line Treatment of Patients With Metastatic Non-Small [NCT05984277]Phase 3900 participants (Anticipated)Interventional2023-10-24Recruiting
A Phase 1 Dose-Escalation and Expansion Study to Assess Safety and Preliminary Antitumor Activity of Debio 0123 in Combination With Carboplatin and Etoposide in Adult Participants With Small Cell Lung Cancer That Recurred or Progressed After Previous Stan [NCT05815160]Phase 154 participants (Anticipated)Interventional2023-05-02Recruiting
A Study of Pemetrexed Plus Carboplatin Followed by Maintenance Pemetrexed vs Paclitaxel Plus Carboplatin and Bevacizumab Followed by Maintenance Bevacizumab in Patients With Advanced NCSLC of Nonsquamous Histology [NCT00948675]Phase 3361 participants (Actual)Interventional2009-09-01Completed
A Phase III Study Comparing Single-Agent Olaparib or the Combination of Cediranib and Olaparib to Standard Platinum-Based Chemotherapy in Women With Recurrent Platinum-Sensitive Ovarian, Fallopian Tube, or Primary Peritoneal Cancer [NCT02446600]Phase 3579 participants (Actual)Interventional2016-03-28Active, not recruiting
Utilizing Response- and Biology-Based Risk Factors to Guide Therapy in Patients With Non-High-Risk Neuroblastoma [NCT02176967]Phase 3621 participants (Anticipated)Interventional2014-08-08Active, not recruiting
Genotype-driven Treatment of Advanced Non-small Cell Lung Cancer Based on mRNA Expression of ERCC1 & RRM1 as First-line Chemotherapy [NCT00736814]Phase 2117 participants (Anticipated)Interventional2008-06-30Recruiting
Protocol for the Study and Treatment of Patients With Intraocular Retinoblastoma [NCT00186888]Phase 3107 participants (Actual)Interventional2005-04-07Active, not recruiting
Phase II Trial of Bexarotene (Targretin) Capsules With Tretinoin and Chemotherapy in Patients With Advanced Non-small-cell Lung Cancer [NCT00514293]Phase 239 participants (Anticipated)Interventional2007-01-31Recruiting
A Phase I Trial of A SRC Kinase Inhibitor, Dasatinib,in Combination With Paclitaxel and Carboplatin in Patients With Advanced or Recurrent Ovarian, Peritoneal, and Tubal Cancer [NCT00672295]Phase 111 participants (Actual)Interventional2007-08-31Completed
Randomized Phase II Study of Biweekly Chemotherapy With Gemcitabine and Carboplatin in Elder Patients With Previously Untreated Advanced Non-Small Cell Lung Cancer [NCT00881296]Phase 260 participants (Actual)Interventional2008-03-31Completed
A Phase II Trial of Carboplatin, Abraxane, and Bevacizumab in Previously Untreated Patients With Advanced Non-Small Cell Lung Cancer [NCT00642759]Phase 236 participants (Actual)Interventional2008-04-30Completed
A Phase II, Double-blind, Placebo-controlled, Multi-centre, Randomised Study of AZD0530 in Patients With Advanced Ovarian Cancer Sensitive to Platinum-based Chemotherapy [NCT00610714]Phase 2211 participants (Actual)Interventional2008-04-30Completed
A Phase II Study of Pemetrexed Plus Carboplatin Combined With Radiation in Patients With Inoperable Locally Advanced Non-small Cell Lung Cancer [NCT00886678]Phase 263 participants (Anticipated)Interventional2008-07-31Active, not recruiting
Randomized Control Trial Comparing Carboplatin 560mg/m2 With 750mg/m2 for Ocular Salvage in Groups C and D Intraocular Retinoblastoma [NCT00889018]60 participants (Anticipated)Interventional2009-04-30Active, not recruiting
A Phase II Study of First-Line Chemotherapy and Panitumumab in Advanced NSCLC Selected by Mutational Status [NCT01038037]Phase 223 participants (Actual)Interventional2010-01-31Terminated(stopped due to "Very low enrollment rate.~Recent studies question the effect of adding panitumumab in this category of patients.~Too high toxicity rate")
A Phase 1 Study Of CP- 870,893 In Combination With Paclitaxel And Carboplatin In Patients With Metastatic Solid Tumors [NCT00607048]Phase 134 participants (Actual)Interventional2007-11-30Completed
Angiogenesis Pathway Gene Polymorphisms Associated With Clinical Outcome in Patients Enrolled in ECOG 4599 [NCT00900172]180 participants (Actual)Observational2008-03-15Completed
A Randomized Phase II Trial to Assess the Efficacy of Paclitaxel and Olaparib in Comparison to Paclitaxel / Carboplatin Followed by Epirubicin/Cyclophosphamide as Neoadjuvant Chemotherapy in Patients With HER2-negative Early Breast Cancer and Homologous R [NCT02789332]Phase 2107 participants (Actual)Interventional2016-09-30Completed
Advanced Non-small Cell Lung Cancer With Chinese Medicine Comprehensive Treatment Plan [NCT02777788]Phase 2/Phase 3120 participants (Anticipated)Interventional2014-09-30Active, not recruiting
A Phase II Study of Pembrolizumab With Carboplatin/Paclitaxel in Patients With Metastatic Melanoma [NCT02617849]Phase 230 participants (Actual)Interventional2016-05-19Active, not recruiting
A Prospective, Belgian Multi-center, Single-arm, Phase II Study of Neoadjuvant Weekly Paclitaxel and Carboplatin Followed by Dose Dense Epirubicin and Cyclophosphamide in Stage II and III Triple Negative Breast Cancer [NCT04224922]Phase 263 participants (Actual)Interventional2015-05-31Completed
A Randomized Phase III Trial of Cisplatin and Tumor Volume Directed Irradiation Followed by Carboplatin and Paclitaxel vs. Carboplatin and Paclitaxel for Optimally Debulked, Advanced Endometrial Carcinoma [NCT00942357]Phase 3813 participants (Actual)Interventional2009-06-29Active, not recruiting
A Single Armed Phase ⅡStudy of Alternating Icotinib and Chemotherapy for Advanced Non-small Cell Lung Cancer With EGFR Mutation [NCT02737774]Phase 260 participants (Anticipated)Interventional2016-04-13Active, not recruiting
A Phase IIb, Randomized, Multicenter, Noncomparative Pilot Study of the Safety & Efficacy of Three Docetaxel-Based Chemotherapy Regimens Plus Bevacizumab ± Trastuzumab for the Adjuvant Treatment of Patients With Node-Positive & High-Risk Node-Negative Bre [NCT00365365]Phase 2214 participants (Actual)Interventional2006-08-31Completed
Open-label Multicenter Multiple Ascending Dose Study to Evaluate Safety, Tolerability and Pharmacokinetics of Quisinostat, a Histone Deacetylase Inhibitor, in Combination With Gemcitabine + Cisplatin Chemotherapy (Second Line for Patients With Non-small C [NCT02728492]Phase 151 participants (Actual)Interventional2013-08-31Completed
Identifying Genetic Predictors of Durable Clinical Benefit to Pembrolizumab in Advanced Non-small Cell Lung Cancer (NSCLC) Alone and in Combination With Chemotherapy. [NCT02710396]Phase 219 participants (Actual)Interventional2016-05-31Terminated(stopped due to Frontline pembrolizumab approved in NSCLC as monotherapy and in combination with chemotherapy representing a new standard of care.)
High Dose Testosterone + Carboplatin in Men With Advanced Prostate Cancer [NCT03522064]Phase 230 participants (Anticipated)Interventional2018-07-30Recruiting
A Multicenter, Phase 2 Study of Gemcitabine-Carboplatin Plus Necitumumab in Chemotherapy-Naïve Patients With Locally Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC) [NCT02941601]Phase 20 participants (Actual)Interventional2016-11-30Withdrawn(stopped due to This was a strategic decision for business planning purposes and not out of concern for patient safety.)
Mobilization of Autologous Peripheral Blood Stem Cells (PBSC) in CD20+ Lymphoma Patients Using RICE, G-CSF (Granulocyte-Colony Stimulating Factor), and Plerixafor [NCT01097057]Phase 220 participants (Actual)Interventional2010-11-09Completed
Post-marketing Clinical Trial of Induction Chemotherapy of Pemetrexed Plus Carboplatin Followed by Pemetrexed Maintenance Therapy for Advanced Nonsquamous Non-small Cell Lung Cancer [NCT01020786]Phase 4109 participants (Actual)Interventional2009-11-30Completed
E7080 in Combination With Carboplatin and Paclitaxel in Patients With Non-small Cell Lung Cancer (NSCLC) [NCT00832819]Phase 128 participants (Actual)Interventional2009-02-28Completed
A Phase III Randomized, Double-Blind, Placebo-controlled Study of Platinum(Cisplatin or Carboplatin) Plus Etoposide With or Without Toripalimab as First Line Therapy in Patients With ExtensiveStage Small Cell Lung Cancer [NCT04012606]Phase 3420 participants (Anticipated)Interventional2019-07-23Recruiting
A Randomised Phase II Open-label Study With a Phase Ib Safety lead-in Cohort of ONCOS-102, an Immune-priming GM-CSF Coding Oncolytic Adenovirus, and Pemetrexed/Cisplatin in Patients With Unresectable Malignant Pleural Mesothelioma [NCT02879669]Phase 1/Phase 231 participants (Actual)Interventional2016-06-30Active, not recruiting
Multicenter, Phase II/III Study of Carboplatin Plus Etoposide With AL3810 in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) [NCT04254471]Phase 2/Phase 3313 participants (Anticipated)Interventional2019-11-14Recruiting
Phase II Trial of Combination Pemetrexed (Alimta) and Carboplatin (Paraplatin) in Platinum Sensitive Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Carcinoma [NCT01001910]Phase 222 participants (Actual)Interventional2008-07-31Completed
An Open-label, Multicenter, Randomized, Phase 2 Study of a Recombinant Human Anti-VEGFR-2 Monoclonal Antibody, IMC-1121B in Combination With Platinum-based Chemotherapy Versus Platinum-based Chemotherapy Alone as First-line Treatment of Patients With Recu [NCT01160744]Phase 2280 participants (Actual)Interventional2010-09-30Completed
Phase 2 Study of Intravenous Administration of Reovirus Serotype 3 - Dearing Strain (REOLYSIN®) in Combination With Paclitaxel and Carboplatin in Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Have KRAS or EGFR Activated Tumors [NCT00861627]Phase 237 participants (Actual)Interventional2009-03-31Completed
A Randomized Phase III Study Comparing Upfront Debulking Surgery Versus Neo-Adjuvant Chemotherapy in Patients With Stage IIIC or IV Epithelial Ovarian Carcinoma [NCT00003636]Phase 3704 participants (Actual)Interventional1998-09-30Completed
A Phase I Study of Ixabepilone in Combination With Carboplatin in Patients With Non-small Cell Lung Cancer as First-line Treatment [NCT00683904]Phase 112 participants (Actual)Interventional2008-06-30Completed
A Randomized Phase 3 Trial of Alimta (Pemetrexed) and Carboplatin Versus Etoposide and Carboplatin in Extensive-Stage Small Cell Lung Cancer [NCT00363415]Phase 3908 participants (Actual)Interventional2006-08-31Completed
Thymosin Alpha 1 Plus Maintenance Therapy With the Standard of Care (SoC) Chemotherapy Plus Cisplatin (or Carboplatin) in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC), EGFR Wild Type [NCT02906150]Phase 2140 participants (Anticipated)Interventional2016-09-30Not yet recruiting
A Phase I/II Study of Intravenous Doxil and Intraperitoneal Carboplatin as Salvage Therapy in Patients With Recurrent Ovarian Cancer [NCT00562185]Phase 1/Phase 20 participants (Actual)Interventional2008-05-31Withdrawn(stopped due to Funding source withdrew funding)
A Multi-center, Randomized, Double-blind, Phase III Trial of SHR-1210 in Combination With Famitinib or Placebo Plus Chemotherapy in Subjects With Non-squamous Non-small-cell Lung Cancer. [NCT04619433]Phase 3560 participants (Anticipated)Interventional2021-02-01Recruiting
Phase 1 Study of Ipilimumab (BMS-734016) in Combination With Paclitaxel and Carboplatin in Japanese Patients With Non-Small Cell Lung Cancer [NCT01165216]Phase 115 participants (Actual)Interventional2010-09-30Completed
Phase II Study of the Response Rate of Induction Chemotherapy With Gemcitabine and Carboplatin for Operable Non-small Cell Lung Cancer Before Surgery [NCT00563160]Phase 250 participants (Anticipated)Interventional2005-05-31Recruiting
Open Label Phase Ib/II, Multicenter Study of the Combination of RO5479599 With Carboplatin and Paclitaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) of Squamous Histology Who Have Not Received Prior Chemotherapy or Targeted [NCT02204345]Phase 1/Phase 212 participants (Actual)Interventional2014-10-31Terminated
A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study Evaluating Safety and Efficacy of the Addition of Veliparib Plus Carboplatin Versus the Addition of Carboplatin to Standard Neoadjuvant Chemotherapy Versus Standard Neoadjuvant Chemotherapy in [NCT02032277]Phase 3634 participants (Actual)Interventional2014-04-02Completed
A Pilot Induction Regimen Incorporating Chimeric 14.18 Antibody (ch14.18, Dinutuximab) (NSC# 764038) and Sargramostim (GM-CSF) for the Treatment of Newly Diagnosed High-Risk Neuroblastoma [NCT03786783]Phase 242 participants (Actual)Interventional2019-01-14Active, not recruiting
PROVE A Randomized Phase II Trial of Standard Carboplatin-based Chemotherapy With or Without Panitumumab in Platinum-sensitive Recurrent Ovarian Cancer [NCT01388621]Phase 2140 participants (Anticipated)Interventional2011-10-31Recruiting
A Phase 2, Randomized, Efficacy and Safety Study of Imprime PGG® Injection in Combination With Bevacizumab and Concomitant Paclitaxel and Carboplatin Therapy in Patients With Previously Untreated Advanced (Stage IIIB or IV) Non-Small Cell Lung Cancer [NCT00874107]Phase 290 participants (Actual)Interventional2009-06-30Completed
A Randomized, Open-label, Multi-center Phase III Study of Erlotinib Versus Gemcitabine/Carboplatin in Chemo-naive Stage IIIB/IV Non-Small Cell Lung Cancer Patients With EGFR Exon 19 or 21 Mutation (Optimal) [NCT00874419]Phase 3165 participants (Actual)Interventional2008-08-31Completed
Efficacy and Safety of Neoadjuvant Therapy With Sintilimab and Apatinib Combined Chemotherapy in Triple-negative Breast Cancer [NCT04722718]Phase 234 participants (Anticipated)Interventional2021-02-01Recruiting
A Phase 2 Study of Polatuzumab Vedotin With Rituximab, Ifosfamide, Carboplatin, and Etoposide (PolaR-ICE) as Initial Salvage Therapy for Relapsed/Refractory Diffuse Large B-cell Lymphoma [NCT04665765]Phase 241 participants (Actual)Interventional2021-01-18Active, not recruiting
Neoadjuvant Chemotherapy in Upper Tract Urothelial Cancer: A Multicentre, Feasibility Pilot Trial [NCT04574960]Phase 314 participants (Anticipated)Interventional2021-02-08Recruiting
A Phase III, Double-Blinded, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Neoadjuvant Treatment With Atezolizumab or Placebo in Combination With Platinum-Based Chemotherapy in Patients With Resectable Stage II, IIIA, or Select IIIB [NCT03456063]Phase 3453 participants (Actual)Interventional2018-04-24Active, not recruiting
Phase I Trial of MK-3475 and Concurrent Chemo/Radiation for the Elimination of Small Cell Lung Cancer [NCT02402920]Phase 183 participants (Actual)Interventional2015-07-22Active, not recruiting
A Randomized Phase 2 Study to Evaluate the Efficacy and Safety for Adjuvant Therapeutic Cancer Vaccine (AST-201, pUMVC3-hIGFBP-2) in Patients With Advanced Ovarian Cancer (Cornerstone-004) [NCT05794659]Phase 298 participants (Anticipated)Interventional2023-11-15Not yet recruiting
A Randomised, Parallel, Double Blinded Study to Compare the Efficacy and Safety of FKB238 to Avastin® In 1st Line Treatment for Patients With Advanced/Recurrent Non Squamous NSCLC in Combination of Paclitaxel and Carboplatin [NCT02810457]Phase 3731 participants (Actual)Interventional2016-09-07Completed
A Phase IIIB, Single Arm Study, of Durvalumab in Combination With Platinum-Etoposide for Untreated Patients With Extensive-Stage Small Cell Lung Cancer Reflecting Real World Clinical Practice in Spain (CANTABRICO). [NCT04712903]Phase 3101 participants (Actual)Interventional2020-12-16Completed
A Phase II Neo-adjuvant Study Assessing TCH (Docetaxel, Carboplatin and Trastuzumab) and TCHL (Docetaxel, Carboplatin, Trastuzumab and Lapatinib) in HER-2 Positive Breast Cancer Patients. [NCT01485926]Phase 2120 participants (Anticipated)Interventional2010-10-31Completed
Concomitant Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Bio-selection For Organ Preservation In Patients With Advanced Laryngeal Cancer [NCT01633541]Phase 255 participants (Actual)Interventional2012-03-31Completed
Phase II Multicenter Study Evaluating the Efficacy of Carboplatin-Etoposide Combination in Hormone-resistant Prostate Cancers With Neuroendocrine Differentiation. [NCT00973882]Phase 260 participants (Actual)Interventional2005-04-30Completed
A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology Of PI3-Kinase Inhibitor GDC-0941 In Combination With Either Paclitaxel And Carboplatin (With or Without Bevacizumab) or Pemetrexed, Cisplatin, And Bevacizumab in Patients With Ad [NCT00974584]Phase 165 participants (Actual)Interventional2009-10-31Completed
Phase 1/2 Study of ZK-Epothilone (ZK-Epo; ZK-219477) in Combination With Carboplatin in Patients With Platinum-sensitive Recurrent Ovarian Cancer [NCT00325351]Phase 245 participants (Actual)Interventional2006-08-24Completed
A Randomized Phase III Comparison of Standard-Dose (60 Gy) Versus High-Dose (74 Gy) Conformal Radiotherapy With Concurrent and Consolidation Carboplatin/Paclitaxel +/- Cetuximab (IND #103444) in Patients With Stage IIIA/IIIB Non-Small Cell Lung Cancer [NCT00533949]Phase 3544 participants (Actual)Interventional2007-11-30Completed
Phase II/III Trial of Simmtecan and 5-FU/LV Regimen (FOLFSIM) Plus Teripalimab Versus EP/EC in Advanced or Metastatic Neuroendocrine Carcinoma [NCT03992911]Phase 2/Phase 3336 participants (Anticipated)Interventional2019-06-19Recruiting
A Phase II Trial of Carboplatin, Paclitaxel, and Nivolumab Induction Therapy Followed by Response-stratified Locoregional Therapy for Patients With Locally Advanced, HPV-negative Head and Neck Cancer. The DEPEND Trial. [NCT03944915]Phase 236 participants (Anticipated)Interventional2019-08-26Recruiting
A Phase II Trial of Carboplatin, Bevacizumab and Pemetrexed in Advanced Non-Small Cell Lung Cancer [NCT00614822]Phase 250 participants (Actual)Interventional2007-11-30Completed
Randomized Phase II Study of Vorinostat or Placebo in Combination With Carboplatin and Paclitaxel for Patients With Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00481078]Phase 294 participants (Actual)Interventional2007-05-31Completed
A Phase II Study of TARCEVA (Erlotinib) in Combination With Chemoradiation in Patients With Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC) [NCT00563784]Phase 268 participants (Actual)Interventional2007-11-30Completed
[NCT00534729]200 participants (Actual)Interventional2007-09-30Completed
[NCT00936156]Phase 268 participants (Actual)Interventional2009-01-31Completed
A Multicenter, Open Label, Randomized Phase II Trial of Presurgical Treatment With Single-Agent Trastuzumab (H) or Lapatinib (Ty) or the Combination of Trastuzumab and Lapatinib (H+Ty), Followed by Six Cycles of Docetaxel (T) and Carboplatin (C) With Tras [NCT00769470]Phase 218 participants (Actual)Interventional2009-04-30Completed
Phase I/II Study of Intra-Arterial Melphalan Given With Intra-Arterial Carboplatin, Osmotic Blood-Brain Barrier Disruption and Delayed Otoprotective Sodium Thiosulfate for Patients With Recurrent or Progressive CNS Embryonal or Germ Cell Tumors [NCT00983398]Phase 1/Phase 217 participants (Actual)Interventional2009-07-09Active, not recruiting
A Randomized Phase III Trial of Paclitaxel Plus Carboplatin Versus Ifosfamide Plus Paclitaxel in Chemotherapy-Naive Patients With Newly Diagnosed Stage I-IV, Persistent or Recurrent Carcinosarcoma (Mixed Mesodermal Tumors) of the Uterus, Fallopian Tube, P [NCT00954174]Phase 3637 participants (Actual)Interventional2009-08-17Active, not recruiting
PreOperative Treatment With chEmotheRapy or chemoRAdiatioN in esophaGeal or gastroEsophageal adenocaRcinoma [NCT01404156]Phase 2/Phase 360 participants (Anticipated)Interventional2015-09-30Recruiting
A Multicenter Phase III Randomized Trial of Adjuvant Therapy for Patients With HER2-Positive Node-Positive or High Risk Node-Negative Breast Cancer Comparing Chemotherapy Plus Trastuzumab With Chemotherapy Plus Trastuzumab Plus Bevacizumab [NCT00625898]Phase 33,509 participants (Actual)Interventional2008-04-30Terminated
A Phase I/II Study of Nab-Paclitaxel and Carboplatin With Concurrent Radiation Therapy for Unresectable Stage III Non-Small-Cell Lung Cancer (NSCLC) [NCT00544648]Phase 1/Phase 213 participants (Actual)Interventional2007-11-30Terminated(stopped due to Ph I completed. Funding became unavailable causing Ph II to cease after two patients were enrolled.)
A Single-arm Phase II Clinical Study Investigating the Addition of Bevacizumab to Carboplatin and Weekly Paclitaxel as First-line Treatment in Patients With Epithelial Ovarian Cancer [NCT00937560]Phase 2190 participants (Actual)Interventional2009-06-25Completed
Albumin-bound Paclitaxel Combined With Carboplatin Versus Epirubicin Combined With Docetaxel as Neoadjuvant Therapy for Triple-negative Breast Cancer: a Multicenter Randomized Controlled Phase IV Clinical Trial [NCT04136782]Phase 4110 participants (Anticipated)Interventional2021-07-19Recruiting
A Phase II Study of Carboplatin (CBDCA), Paclitaxel (TAXOL), and Everolimus (RAD001) in Previously Untreated Patients With Measurable Disease With Cancer of Unknown Primary (CUP) [NCT00936702]Phase 246 participants (Actual)Interventional2009-09-30Completed
Phase II Trial of BAY 43-9006 (Sorafenib; NSC-724772) in Combination With Carboplatin and Paclitaxel in Patients With Metastatic Uveal Melanoma [NCT00329641]Phase 225 participants (Actual)Interventional2011-02-28Completed
Pilot Study of the Safety and Feasibility of Administering Concurrent Chemotherapy and Accelerated Hypofractionated Radiation Therapy in the Treatment of Medically Inoperable T2A-T4 N0 Non-small Cell Lung Cancer. [NCT02619448]Early Phase 112 participants (Anticipated)Interventional2014-12-31Recruiting
A Phase Ib, Open-Label Study Evaluating the Safety and Pharmacokinetics of Atezolizumab (Anti-PD-L1 Antibody) in Combination With Trastuzumab Emtansine or With Trastuzumab and Pertuzumab (With and Without Docetaxel) in Patients With HER2-Positive Breast C [NCT02605915]Phase 198 participants (Anticipated)Interventional2015-12-31Completed
Phase II Trial of Ixabepilone Plus Carboplatin in Patients With Metastatic Breast Cancer: The ECLIPSE Study [NCT01075100]Phase 2103 participants (Actual)Interventional2010-01-31Completed
Neuroblastoma Protocol 2005: Therapy for Children With Advanced Stage High-Risk Neuroblastoma [NCT00135135]Phase 223 participants (Actual)Interventional2005-08-31Completed
Phase II Trial of Gemcitabine and Cisplatin/Carboplatin (GC) Plus Erlotinib in Patients With Recurrent and/or Metastatic Nasopharyngeal Cancer [NCT00603915]Phase 220 participants (Actual)Interventional2006-06-30Completed
Phase III Randomized Trial of Single vs. Tandem Myeloablative Consolidation Therapy for High-Risk Neuroblastoma [NCT00567567]Phase 3665 participants (Actual)Interventional2007-11-05Completed
A Randomized, Phase III Trial of ABI-007 and Carboplatin Compared With Taxol and Carboplatin as First-Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00540514]Phase 31,052 participants (Actual)Interventional2007-11-01Completed
Phase 2 Study of Intravenous Administration of a Wild-Type Reovirus (REOLYSIN®) in Combination With Paclitaxel and Carboplatin in Patients With Platinum-Refractory Metastatic and/or Recurrent Squamous Cell Carcinoma of the Head and Neck. [NCT00753038]Phase 214 participants (Actual)Interventional2008-08-31Completed
Circulating Tumor DNA Guiding (Olaparib) Lynparza® Treatment in Ovarian [NCT02822157]Phase 2160 participants (Actual)Interventional2016-08-31Active, not recruiting
A Prospective, Single-arm, Single-center, Exploratory Study of the Safety and Efficacy of Serplulimab Combined With Chemotherapy in Patients With Resectable Esophageal Squamous Cell Carcinoma [NCT05659251]Phase 257 participants (Anticipated)Interventional2022-12-01Recruiting
Autologous Stem Cell Rescue With CD133+ Selected Hematopoietic Progenitor Cells in Patients With High-Risk Neuroblastoma [NCT00539500]Phase 2/Phase 33 participants (Actual)Interventional2007-10-31Terminated(stopped due to Slow Accrual.)
A Randomized Phase II Study of Gemcitabine and Carboplatin With or Without AZD2171 as First-Line Therapy in Advanced Non-Small Cell Lung Cancer [NCT00326599]Phase 2101 participants (Actual)Interventional2007-06-30Completed
Dose Dense Administration of Paclitaxel and Carboplatin Combination as 1st Line Treatment in Patients With Ovarian Carcinoma [NCT00750386]Phase 1/Phase 250 participants (Anticipated)Interventional2008-01-31Completed
A Randomized Phase 3 Multicenter Open-Label Study to Compare the Efficacy of TAK-788 as First-Line Treatment Versus Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations [NCT04129502]Phase 3354 participants (Actual)Interventional2020-01-10Active, not recruiting
A Multicenter Phase I/II Trial of a Novel MDM2 Inhibitor (APG-115) in p53 Wild-type Salivary Gland Carcinoma [NCT03781986]Phase 1/Phase 234 participants (Anticipated)Interventional2019-10-28Recruiting
Phase IB Trial of Induction Nivolumab or Nivolumab/Relatlimab Prior to Concurrent Chemoradiation in Patients With Operable Stage II/III Esophageal/ Gastroesophageal Junction Cancer [NCT03044613]Phase 132 participants (Actual)Interventional2017-07-11Active, not recruiting
A Phase II, Single-center, Open-Label, Randomized Study of Gemcitabine Plus Cisplatin (GP) Versus Gemcitabine Plus Carboplatin (GC) as First-Line Treatment in Patients With Advanced Triple-Negative Breast Cancer [NCT02341911]Phase 2150 participants (Anticipated)Interventional2015-01-31Recruiting
A Phase 1b Study of LY3039478 in Combination With Other Anticancer Agents in Patients With Advanced or Metastatic Solid Tumors [NCT02784795]Phase 194 participants (Actual)Interventional2016-11-04Completed
Phase II Randomized, Open-Label Study of Cetuximab and Bevacizumab in Combination With Paclitaxel and Carboplatin in Patients With Stage IIIB/IV Non-Small Cell Lung Cancer [NCT00343291]Phase 2121 participants (Actual)Interventional2006-12-31Completed
Phase II Trial of Bevacizumab in Combination With Gemcitabine and Carboplatin in Patients With Newly Diagnosed Non-Small Cell Lung Cancer (Excluding Squamous Cell Carcinoma) [NCT00323869]Phase 248 participants (Actual)Interventional2006-06-30Completed
Liver Resection Versus Transarterial Chemoembolization for the Treatment of Intermediate-stage Hepatocellular Carcinoma: a Prospective Non-randomized Trial [NCT02755311]Phase 3198 participants (Anticipated)Interventional2014-03-31Recruiting
Blood-borne Assessment of Stromal Activation in Esophageal Adenocarcinoma to Guide Tocilizumab Therapy: a Randomized Phase II Proof-of-concept Study [NCT04554771]Phase 241 participants (Actual)Interventional2021-01-27Active, not recruiting
A Multicenter Randomized Phase II Study of Docetaxel/Carboplatin Versus Docetaxel/Pegylated Liposomal Doxorubicin as Second Line Treatment in Patients With Platinum Sensitive Disease [NCT00758732]Phase 234 participants (Actual)Interventional2005-10-31Terminated(stopped due to Poor accrual)
A Phase I/II, Open-Label, Multicenter, Two-Arm, Feasibility Study of Pazopanib, Carboplatin, and Paclitaxel in Women With Newly Diagnosed, Previously Untreated, Gynaecological Tumors [NCT00561795]Phase 212 participants (Actual)Interventional2007-09-30Completed
A Phase 1b, Multicenter, 2-Part, Open-Label Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Immunotherapy With or Without Carboplatin in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (Tropion-Lung04) [NCT04612751]Phase 1321 participants (Anticipated)Interventional2021-02-02Recruiting
Randomized Phase II Study of Platinum-Taxane-Cetrelimab Induction Followed by Niraparib Plus or Minus Cetrelimab Maintenance in Men With Aggressive Variant Prostate Cancers [NCT04592237]Phase 2120 participants (Anticipated)Interventional2020-12-29Recruiting
A Phase 3 Randomized Non-Inferiority Study of Carboplatin and Vincristine Versus Selumetinib (NSC# 748727) in Newly Diagnosed or Previously Untreated Low-Grade Glioma (LGG) Not Associated With BRAFV600E Mutations or Systemic Neurofibromatosis Type 1 (NF1) [NCT04166409]Phase 3220 participants (Anticipated)Interventional2020-01-31Recruiting
Phase 1/1b Study Investigating Safety, Tolerability, PK and Antitumor Activity of Anti-TIGIT Monoclonal Antibody BGB-A1217 in Combination With Anti-PD-1 Monoclonal Antibody Tislelizumab in Patients With Advanced Solid Tumors [NCT04047862]Phase 1542 participants (Anticipated)Interventional2019-08-26Recruiting
A Phase III, Randomized, Multicenter,Open-Label, Comparative Study to Determine the Efficacy of Durvalumab or Durvalumab and Tremelimumab in Combination With Platinum-Based Chemotherapy for the First-Line Treatment in Patients With Extensive Disease Small [NCT03043872]Phase 3987 participants (Actual)Interventional2017-03-27Active, not recruiting
A Phase I/II Trial of Abraxane in Combination With Carboplatin, Erbitux and Intensity Modulated Radiation Therapy (IMRT)for Treatment of Locally Advanced Squamous Cancer of the Head and Neck [NCT00570674]Phase 1/Phase 229 participants (Actual)Interventional2007-11-30Terminated(stopped due to The study did not continue to phase II due to the importance of HPV status as a prognostic factor to guide treatment decisions.)
A Phase I Safety Study of Farletuzumab (MORAb-003), Carboplatin and Pegylated Liposomal Doxorubicin (PLD) in Subjects With Platinum-sensitive Ovarian Cancer [NCT01004380]Phase 115 participants (Actual)Interventional2009-11-30Completed
A Phase III Randomized, Open-Label, Multi-Center Study of Durvalumab (MEDI4736) Versus Standard of Care (SoC) Platinum-Based Chemotherapy as First Line Treatment in Patients With PD-L1-High Expression Advanced Non Small-Cell Lung Cancer [NCT03003962]Phase 3669 participants (Actual)Interventional2017-01-02Active, not recruiting
A Phase II, Randomized, Multicenter Study to Assess the Efficacy of Nab-paclitaxel-based Doublet as First Line Therapy in Patients With Cancer of Unknown Primary (CUP): The AGNOSTOS Trial [NCT02607202]Phase 2120 participants (Anticipated)Interventional2015-03-31Recruiting
Multicenter, Randomised, Double-blind Phase III Trial to Investigate the Efficacy and Safety of BIBF 1120 in Combination With Carboplatin and Paclitaxel Compared to Placebo Plus Carboplatin and Paclitaxel in Patients With Advanced Ovarian Cancer [NCT01015118]Phase 31,366 participants (Actual)Interventional2009-11-17Completed
PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study [NCT04115410]4,724 participants (Anticipated)Observational2020-07-01Not yet recruiting
Cetuximab, Paclitaxel, Carboplatin and Radiation for Esophageal, Gastroesophageal Junction and Gastric Cancer BMS#CA225091 [NCT00439608]Phase 260 participants (Actual)Interventional2004-10-31Completed
Efficacy and Safety of Rh-endostatin（Endostar）Combined With Platinum-based Doublet Chemotherapy and Pembrolizumab as First Line Therapy in Patients With Advanced or Metastatic Non-small-cell Lung Cancer [NCT04094909]Phase 2186 participants (Anticipated)Interventional2020-02-06Not yet recruiting
An Open Label, Randomized, Phase I/II Study of DMXAA in Combination With Carboplatin and Paclitaxel in Patients With Locally Advanced and Metastatic Non-Small Cell Lung Cancer [NCT00832494]Phase 1/Phase 2105 participants (Actual)Interventional2004-09-30Completed
Phase III Trail of Breast Cancer Shrinkage Modes After Neoadjuvant Chemotherapy With Whole-mount Serial Sections and Three-dimensional Pathological and MRI Reconstruction [NCT01917578]Phase 34 participants (Anticipated)Interventional2008-08-31Recruiting
TAK-676 Alone and in Combination(s) With Carboplatin, 5-Fluorouracil, and Paclitaxel in Patients With Head and Neck Squamous Cell Carcinoma [NCT06062602]Early Phase 115 participants (Actual)Interventional2021-07-26Completed
A Randomised Feasibility Study of Extended Chemotherapy With Neoadjuvant Carboplatin, Then Surgery Followed by Adjuvant Paclitaxel and Gemcitabine Verses Neoadjuvant Gemcitabine and Carboplatin, Then Surgery, Followed by Adjuvant Paclitaxel [NCT00838656]Phase 288 participants (Anticipated)Interventional2007-10-31Active, not recruiting
Phase III Randomized Trial Comparing Overall Survival After Photon Versus Proton Chemoradiotherapy for Inoperable Stage II-IIIB NSCLC [NCT01993810]Phase 3330 participants (Actual)Interventional2014-02-03Active, not recruiting
Phase I Trial of Bevacizumab and Temsirolimus in Combination With 1) Carboplatin, 2) Paclitaxel, 3) Sorafenib for the Treatment of Advanced Cancer [NCT01187199]Phase 1278 participants (Anticipated)Interventional2010-08-19Active, not recruiting
EWOC-1 Trial: Multicenter, Randomized Trial of Carboplatin +/- Paclitaxel in Vulnerable Elderly Patients With Stage III-IV Advanced Ovarian Cancer [NCT02001272]Phase 2120 participants (Actual)Interventional2013-12-31Completed
Phase I / II Study of Sequential High-dose Chemotherapy With Stem Cell Support in Children Younger Than 5 Years of Age With High-risk Medulloblastoma [NCT02025881]Phase 1/Phase 229 participants (Actual)Interventional2013-09-14Active, not recruiting
Phase 2 Randomized Study of Different Neoadjuvant Regimens in Subtypes of Breast Cancer [NCT02041338]Phase 2200 participants (Anticipated)Interventional2014-01-31Recruiting
Phase I/II Trial Using a Biomarker-Integrated Approach of Targeted Therapy for Lung Cancer Elimination Plus External Beam Radiation Therapy (BATTLE-XRT) [NCT02044601]Phase 1/Phase 20 participants (Actual)Interventional2014-06-30Withdrawn
Carboplatin, Gemcitabine, and Mifepristone for Advanced Breast Cancer and Recurrent or Persistent Epithelial Ovarian Cancer [NCT02046421]Phase 131 participants (Actual)Interventional2013-11-30Completed
Multicenter, Open-Ended, Double-Blind, Placebo-Controlled, Phase III Study of AE-941 in Addition to Combined Modality Treatment (Chemotherapy/Radiotherapy) for Locally Advanced Unresectable Non-Small Cell Lung Cancer [NCT00005838]Phase 3756 participants (Actual)Interventional2000-03-31Completed
Phase I/II Trial of Pyrazoloacridine and Carboplatin in Patients With Recurrent Glioma [NCT00005976]Phase 260 participants (Actual)Interventional2000-05-31Completed
Autotransplantation and Her 2 Neu Antibody Immunotherapy in Advanced Breast Cancer [NCT00006123]Phase 1/Phase 20 participants (Actual)Interventional2000-07-31Withdrawn(stopped due to Never started)
A Randomized，Double-blind，Controlled，Multi-center Phase III Clinical Study Evaluating SHR-1701 or Placebo Plus Chemotherapy With or Without BP102 (Bevacizumab) as First-Line Treatment in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer [NCT05179239]Phase 3572 participants (Anticipated)Interventional2022-02-26Recruiting
Randomized Phase III Trial Of Carboplatin And Paclitaxel Plus Tirapazamine Versus Carboplatin And Paclitaxel In Patients With Advanced Non-Small Cell Lung Cancer [NCT00006484]Phase 30 participants Interventional2000-11-30Completed
TREATMENT OF CHILDREN AND YOUNG ADULTS WITH RECURRENT/REFRACTORY SOLID TUMORS WITH HIGH DOSE ETOPOSIDE AND CARBOPLATIN PLUS ESCALATING DOSE CYCLOPHOSPHAMIDE, FOLLOWED BY HEMATOPOIETIC RESCUE USING AUTOLOGOUS CD34+ SELECTED BLOOD STEM CELLS: A PILOT STUDY [NCT00007813]Phase 121 participants (Actual)Interventional1997-05-31Completed
A Phase I Trial of Subcutaneous And/Or Oral Calcitriol [(1,25-COH)2D3] and Carboplatin in Advanced Solid Tumors [NCT00008086]Phase 10 participants Interventional1996-01-31Completed
Phase I Study Of Gemcitabine, Docetaxel And Carboplatin, With And Without Filrastim Support, Combination Chemotherapy In Patients With Advanced Non-Hematological Malignancies [NCT00008125]Phase 125 participants (Actual)Interventional1998-03-31Completed
High-Dose Chemotherapy Followed By Autologous Hematopoietic Stem Cell Support And One Of Two Regimens Aimed At Modifying Immune Reconstitution In Women With High Risk Stage 2 And Stage 3 Breast Cancer [NCT00008203]Phase 30 participants Interventional1996-05-31Completed
Decitabine Plus Carboplatin in the Treatment of Metastatic Triple Negative Breast Cancer [NCT03295552]Phase 212 participants (Actual)Interventional2017-11-15Terminated(stopped due to Slow enrollment.)
A Phase 2 Study of Preoperative Pembrolizumab and Chemotherapy Followed by Adjuvant Pembrolizumab in Resectable Locoregionally Recurrent Head and Neck Squamous Cell Carcinoma [NCT05726370]Phase 228 participants (Anticipated)Interventional2023-05-20Recruiting
An Open-label, Multi-center, Phase II Umbrella Study to Assess Efficacy of Targeted Therapy or Immunotherapy Directed by Next Generation Sequencing (NGS) in Chinese Patients With Advanced NSCLC (TRUMP) [NCT03574402]Phase 2400 participants (Anticipated)Interventional2018-07-09Recruiting
A Phase 1, Multicenter, Dose-Escalation Study to Investigate the Safety and Tolerability of ADH-1 in Combination With 1) Carboplatin or 2) Docetaxel or 3) Capecitabine in Subjects With N-Cadherin Positive, Advanced Solid Tumors (Adherex Protocol Number AH [NCT00390676]Phase 10 participants Interventional2006-11-30Completed
Phase II Evaluation of Trastuzumab (Herceptin), Paclitaxel, Carboplatin, and Gemcitabine in the Treatment of Advanced Urothelial Cancer [NCT00005831]Phase 240 participants (Anticipated)Interventional2000-03-31Completed
Dose Intensification Phase II Study in Refractory Germ Cell Tumors With Relapse and Bad Prognosis. TICE Protocol : Paclitaxel and Ifosfamide Followed by Carboplatine and Etoposide Intensification With Individual Carboplatine Dose Adjustment. [NCT00864318]Phase 2101 participants (Actual)Interventional2009-03-13Completed
A Phase I/II Trial of CPT-11 With Carboplatin in Patients With Glioblastoma Multiforme Prior to Radiation Therapy [NCT00010036]Phase 20 participants Interventional1999-05-31Completed
Phase II Trial of Docetaxel and Carboplatin as First-Line Therapy for Metastatic Breast Cancer [NCT00005963]Phase 253 participants (Actual)Interventional2000-11-30Completed
Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study [NCT00005978]Phase 10 participants Interventional2000-05-31Completed
Phase II Trial Exploring the Feasibility of Adjuvant Carboplatin/Docetaxel in Curatively Resected Stage I-IIIA Non-Small Cell Lung Cancer [NCT00280735]Phase 275 participants (Actual)Interventional2004-05-31Completed
A Phase I Study of Gemcitabine, Carboplatin or Gemcitabine, Paclitaxel and Radiation Therapy Followed by Adjuvant Chemotherapy for Patients With Favorable Prognosis Inoperable Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC) [NCT00016315]Phase 135 participants (Actual)Interventional2001-05-31Completed
A Phase I Study Of Genasense, A Bcl-2 Antisense Oligonucleotide, Combined With Carboplatin And Etoposide In Patients With Small Cell Lung Cancer [NCT00017251]Phase 112 participants (Actual)Interventional2001-04-30Completed
A Pilot Study Of Tandem High Dose Chemotherapy With Stem Cell Rescue Following Induction Therapy In Children With High Risk Neuroblastoma [NCT00017368]Phase 242 participants (Actual)Interventional2001-04-30Completed
Paclitaxel, Carboplatin and Radiotherapy as Induction Therapy in Locally Advanced Head and Neck Cancer [NCT00176254]Phase 240 participants (Actual)Interventional2000-05-31Completed
A Phase I Trial of Carboplatin and Abraxane in Patients With Solid Tumors [NCT00520000]Phase 147 participants (Actual)Interventional2004-12-31Completed
Neoadjuvant Chemotherapy With 3x Epirubicin/Docetaxel Followed by 3x Carboplatin/Docetaxel in Patients With Primary Breast Cancer [NCT00527449]Phase 250 participants (Actual)Interventional2006-05-31Completed
Phase I Study Of SU011248 In Combination With Pemetrexed, Pemetrexed/Cisplatin And Pemetrexed/Carboplatin In Patients With Advanced Solid Malignancies [NCT00528619]Phase 196 participants (Actual)Interventional2006-11-30Completed
Determination of Carboplatin's Optimal Plasmatic Exposure [NCT00145028]400 participants (Anticipated)Interventional2005-05-31Completed
A Phase 1 Dose-Escalation and Phase 2 Randomized, Open-Label Study of Nivolumab and Veliparib in Combination With Platinum Doublet Chemotherapy in Subjects With Metastatic or Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT02944396]Phase 125 participants (Actual)Interventional2016-12-23Completed
[NCT00170664]Phase 2129 participants (Actual)Interventional1999-01-31Completed
"A Translational Randomized Phase III Study Exploring the Effect of the Addition of Capecitabine to Carboplatine Based Chemotherapy in Early Triple Negative Breast Cancer" [NCT04335669]Phase 3920 participants (Anticipated)Interventional2019-12-20Recruiting
A Pilot Study of Neoadjuvant Biweekly Doxorubicin and Cyclophosphamide (AC) With GMCSF Followed by Weekly Carboplatin/Paclitaxel With Plus or Minus Trastuzumab (TC ± H) in the Treatment of Breast Cancer [NCT00256243]Phase 248 participants (Actual)Interventional2004-04-30Completed
Phase III Randomized Multicentre Trial of Carboplatin + Liposomal Doxorubicin vs Carboplatin + Paclitaxel in Patients With Ovarian Cancer [NCT00326456]Phase 3820 participants (Actual)Interventional2003-01-01Active, not recruiting
Phase II Evaluation of Trastuzumab (Herceptin), Paclitaxel, Carboplatin, and Gemcitabine in the Treatment of Advanced Urothelial Cancer [NCT00151034]Phase 233 participants (Actual)Interventional2000-09-30Completed
Postoperative Adjuvant Chemotherapy in Early-stage Cervical Cancer That Not Meet Criteria of Adjuvant Therapeutic According to NCCN Guideline：A Prospective Multicenter Randomized Controlled Clinical Trial [NCT04723875]Phase 3306 participants (Anticipated)Interventional2021-02-01Recruiting
A Phase 1 Study of R-(-)-Gossypol (Ascenta's AT-101) in Combination With Paclitaxel and Carboplatin in Solid Tumors [NCT00891072]Phase 136 participants (Actual)Interventional2009-07-31Completed
A Phase II Study of Sorafenib in Combination With Carboplatin and Docetaxel in the First Line Treatment of Stage IIIB/IV Non-Small Cell Lung Cancer [NCT00647426]Phase 27 participants (Actual)Interventional2007-11-30Completed
Q3week Carboplatin With Weekly Abraxaneä And Avastin + Subsequent Dose-Dense Ac With Avastin As Neoadjuvant Therapy In Resectable And Unresectable (Stage Iia-Iiib) Her2-Negative Breast Cancer [NCT00723125]Phase 260 participants (Actual)Interventional2008-09-30Completed
A Phase Two Trial of Neoadjuvant ABI-007, Carboplatin and Gemcitabine in Patients With Locally Advanced Carcinoma of the Bladder [NCT00585689]Phase 229 participants (Actual)Interventional2007-12-31Completed
Docetaxel and Carboplatin Followed by a Dose-Ranging Study of Oral Capecitabine, Weekly Docetaxel, and Concomitant External Beam Radiotherapy for the Treatment of Patients With Stage II-III Carcinoma of the Esophagus and Gastro-Esophageal Junction [NCT00153881]Phase 144 participants (Actual)Interventional2000-02-29Completed
A Modified Two Stage Phase II Study of Combination Abraxane and Radiation for Stage III Non-Small Cell Lung Cancer [NCT00903942]Phase 20 participants (Actual)Interventional2008-03-31Withdrawn(stopped due to funding was withdrawn from Drug company)
Phase II Trial of Sintilimab, an Anti-PD-1 Monoclonal Antibody, in Combination With Combination Carboplatin and Nab-paclitaxel , as a Novel Neoadjuvant Pre-Surgical Therapy for Salivary Gland Malignant Neoplasms [NCT05000892]Phase 215 participants (Anticipated)Interventional2021-12-10Recruiting
A Phase II Study of Paclitaxel and Carboplatin in Patients With Intermediate-Risk Adenocarcinoma of the Endometrium [NCT00584909]Phase 213 participants (Actual)Interventional2006-03-31Terminated(stopped due to low accrual)
A Phase II Pilot Study of Estramustine, Docetaxel, and Carboplatin for Patients With Hormone Refractory Prostate Cancer Progressing After Mitoxantrone-Based Chemotherapy. [NCT00183924]Phase 220 participants (Actual)Interventional2001-03-31Completed
Randomized Phase II Trial to Outline the Efficacy of Gemcitabine Containing Regimens (Gemcitabine/Carboplatin and Gemcitabine/Paclitaxel) When Used as Preoperative Chemotherapy In Patients With Stage I and II NSCLC [NCT00191256]Phase 277 participants Interventional2001-06-30Completed
Protocol H6Q-MC-S034(a) Randomized, Double-Blind, Phase 2 Study of Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin Versus Pemetrexed + Carboplatin + Bevacizumab + Placebo in Chemonaive Patients With Stage IIIB or IV Non-Small Cell Lung Cancer [NCT00533429]Phase 240 participants (Actual)Interventional2007-10-31Completed
Phase I Clinical Study of Autologous CIK Cell Immunotherapy Combination With PD-1 Inhibitor and Chemotherapy in the First-line Treatment of IIIB/IIIC/IV Non-Small Cell Lung Cancer [NCT03987867]Phase 130 participants (Anticipated)Interventional2019-06-01Recruiting
A Phase II Study of Carboplatin and Paclitaxel in Elderly Women With Newly Diagnosed Ovarian, Peritoneal, or Fallopian Cancer [NCT00322881]Phase 212 participants (Actual)Interventional2006-04-30Terminated(stopped due to Early closure based on audit by study investigators after 3 patients died on study.)
A Phase II Trial of Carboplatin and Irinotecan (CPT-11) as First-Line Therapy for Patients With Extensive Stage Small Cell Lung Cancer [NCT00469898]Phase 250 participants (Actual)Interventional2003-12-31Completed
Phase I/II Trial of Sequential Paclitaxel/Ifosfamide Followed by Dose-Escalated, Dose-Intensive Carboplatin, Paclitaxel and Ifosfamide With Stem Cell Support in Cisplatin-Resistant Germ Cell Tumor Patients [NCT00423852]Phase 1/Phase 226 participants (Actual)Interventional2006-08-31Completed
An Open-Label, Single-Arm, Phase II Study of IV Weekly (Days 1 and 8 Every 21 Days) HYCAMTIN in Combination With Carboplatin (Day 1 Every 21 Days) as Second-Line Therapy in Subjects With Potentially Platinum-Sensitive Relapsed Ovarian Cancer [NCT00316173]Phase 277 participants (Actual)Interventional2005-03-31Completed
A Phase II, Open-Label, Multicenter, Pilot Study of the Safety & Efficacy of Two Docetaxel-Based Regimens Plus Bevacizumab for the Adjuvant Treatment of Subjects With Node Positive or High Risk Node Negative Breast Cancer [NCT00446030]Phase 2127 participants (Actual)Interventional2007-03-31Completed
Concurrent Nab--paclitaxel/Carboplatin and Thoracic Radiotherapy in Inoperable Stage III Squamous Cell Lung Cancer [NCT03802058]Phase 224 participants (Actual)Interventional2019-03-20Terminated(stopped due to The study was halted because enrollment was too slow)
Paclitaxel/Carboplatin Combined With Intermittent Gefitinib in Patients With Untreated Advanced Non-small Cell Lung Cancer: A Phase Ⅱa Trial [NCT01024712]Phase 226 participants (Anticipated)Interventional2009-05-31Recruiting
A Phase III, Multicenter, Randomized, Blinded, Placebo-controlled Trial of Carboplatin and Gemcitabine Plus Bevacizumab in Patients With Platinum-sensitive Recurrent Ovary, Primary Peritoneal, or Fallopian Tube Carcinoma [NCT00434642]Phase 3484 participants (Actual)Interventional2007-04-30Completed
A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Efficacy and Safety of Bevacizumab in Combination With Carboplatin and Paclitaxel Chemotherapy for the First-Line Treatment of Patients With Metastatic Melanoma [NCT00434252]Phase 2214 participants (Actual)Interventional2007-02-28Completed
Phase II Trial of Carboplatin and Pemetrexed Plus Bevacizumab in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer [NCT00234052]Phase 251 participants (Actual)Interventional2005-07-28Completed
Phase II Study of Purging of Circulating Tumor Cells (CTCs) From Metastatic Breast Cancer Patients [NCT00429182]Phase 232 participants (Actual)Interventional2007-06-30Completed
A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY 43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC) [NCT00300885]Phase 3926 participants (Actual)Interventional2006-02-28Terminated(stopped due to Based on the results of the interim analysis, it was determined that the study would not meet its primary efficacy endpoint and the study was terminated early.)
A Phase Ib Open-Label, Two-Arm, Dose-Finding Study of E7389 in Combination With Carboplatin in Patients With Solid Tumors [NCT00268905]Phase 164 participants (Actual)Interventional2006-10-31Completed
A Phase II Trial of Preoperative Radiation and Chemotherapy (Pemetrexed and Carboplatin) for Locally Advanced Esophageal Cancer [NCT00268437]Phase 227 participants (Actual)Interventional2006-04-30Terminated(stopped due to Trial closed early because, during an interim analysis, the primary endpoint fell short.)
A Prospective Observational Study of the Efficacy and Safety of CPT-11 Plus Platinum Analogues Regimens for UGT1A1 Genotype Guided Patients With Several Solid Tumors [NCT01040312]321 participants (Actual)Observational2009-10-15Completed
Phase II Study of Pegylated Liposomal Doxorubicin and Carboplatin as First Line Treatment for Patients With Advanced Non-small Cell Lung Cancer [NCT01051362]Phase 248 participants (Anticipated)Interventional2006-02-28Recruiting
Phase I/II Trial of Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Cancer [NCT03490292]Phase 1/Phase 222 participants (Actual)Interventional2018-05-29Active, not recruiting
A Randomized, Phase 2, Placebo-Controlled, Double-Blinded Study With and Without Enzastaurin in Combination With Paclitaxel and Carboplatin as First-Line Treatment, Followed by Maintenance Treatment in Advanced Ovarian Cancer [NCT00391118]Phase 2153 participants (Actual)Interventional2006-11-30Completed
A Randomized, Double Blind, Parallel, Three Arm Trial Evaluating the Efficacy and Safety of Ipilimumab (BMS-734016) in Combination With Paclitaxel/Carboplatin Compared to Paclitaxel/Carboplatin Alone in Previously Untreated Subjects With Lung Cancer [NCT00527735]Phase 2334 participants (Actual)Interventional2008-02-29Completed
A Randomized Phase II Trial of Avastin (A) or Avastin and Erlotinib (AE) as First Line Consolidation Chemotherapy After Carboplatin, Paclitaxel, and Avastin (CTA) Induction Therapy for Newly Diagnosed Advanced Ovarian, Fallopian Tube, Primary Peritoneal C [NCT00520013]Phase 260 participants (Actual)Interventional2007-08-31Completed
Treatment of High Risk Renal Tumors: A Groupwide Phase II Study [NCT00335556]Phase 2291 participants (Actual)Interventional2006-06-30Completed
Phase 2 Trial of NOV-002 With Carboplatin in Women With Recurrent and Platinum Resistant Tumors of Mullerian Origin [NCT00345540]Phase 215 participants (Actual)Interventional2006-07-31Completed
A Randomized Multicenter Phase III Study of Taxane/Carboplatin/Cetuximab Versus Taxane/Carboplatin as First-Line Treatment for Patients With Advanced/Metastatic Non-Small Cell Lung Cancer [NCT00112294]Phase 3755 participants (Actual)Interventional2004-12-31Completed
Risk-Adapted High Dose Chemoradiotherapy and Autologous Stem Cell Transplantation for Patients With Relapsed and Primary Refractory Hodgkin's Lymphoma [NCT00255723]Phase 298 participants (Actual)Interventional2004-04-30Completed
A Phase II Study of Carboplatin and Bevacizumab (Avastin) Combination Therapy for ER Negative, PR Negative, and HER2/Neu Negative Metastatic Breast Cancer [NCT00517361]Phase 211 participants (Actual)Interventional2007-08-31Terminated(stopped due to This study has been terminated due to poor accrual)
A Phase I Pharmacokinetic Study of Intraperitoneal CTEP-Supplied Agent Bortezomib (PS-341, NSC 681239) and Carboplatin (NSC# 241240) in Patients With Persistent or Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer [NCT01074411]Phase 133 participants (Actual)Interventional2010-04-05Completed
A Phase III, Open-label, Randomised Study of Neoadjuvant Datopotamab Deruxtecan (Dato-DXd) Plus Durvalumab Followed by Adjuvant Durvalumab With or Without Chemotherapy Versus Neoadjuvant Pembrolizumab Plus Chemotherapy Followed by Adjuvant Pembrolizumab W [NCT06112379]Phase 31,728 participants (Anticipated)Interventional2023-11-14Recruiting
Phase II Study of Lorlatinib in Combination With Chemotherapy in Participants With Metastatic Anaplastic Lymphoma Kinase Positive (ALK+) Non-small Cell Lung Cancer (NSCLC) Who Progressed on Single-agent Lorlatinib [NCT05948462]Phase 20 participants (Actual)Interventional2023-11-30Withdrawn(stopped due to Study withdrawn by pharmaceutical funding partner)
A Phase Ib/II, Open-Label, Multicenter Study Evaluating the Safety, Activity, and Pharmacokinetics of Divarasib in Combination With Other Anti-Cancer Therapies in Patients With Previously Untreated Advanced Or Metastatic Non-Small Cell Lung Cancer With a [NCT05789082]Phase 1/Phase 296 participants (Anticipated)Interventional2023-06-20Recruiting
Dose-finding Phase 1 Trial: Evaluating Safety and Biomarkers Using DK210 (EGFR) for Inoperable Locally Advanced and/or Metastatic EGFR+ Tumors With Progressive Disease Failing Systemic Therapy [NCT05704985]Phase 160 participants (Anticipated)Interventional2023-04-03Recruiting
A Randomized Phase 3 Study Assessing the Efficacy and Safety of Olvi-Vec Followed by Platinum-doublet Chemotherapy and Bevacizumab Compared With Platinum-doublet Chemotherapy and Bevacizumab in Women With Platinum-Resistant/Refractory Ovarian Cancer (OnPr [NCT05281471]Phase 3186 participants (Anticipated)Interventional2022-08-31Recruiting
A Phase I Study of Gemcitabine, Carboplatin and Lenalidomide (GCL) for Treatment of Patients With Advanced/Metastatic Urothelial Carcinoma (UC) and Other Solid Tumors [NCT01352962]Phase 118 participants (Actual)Interventional2011-09-26Completed
A Randomized, Double-Blind, Phase 3 Study of MK-7684A in Combination With Chemotherapy Versus Pembrolizumab Plus Chemotherapy as First Line Treatment for Participants With Metastatic Non-Small Cell Lung Cancer [NCT05226598]Phase 3700 participants (Anticipated)Interventional2022-03-24Active, not recruiting
A Phase 3 Global, Multicenter, Double-Blind Randomized Study of Carboplatin-Paclitaxel With INCMGA00012 or Placebo in Participants With Inoperable Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Anal Canal Not Previously Treated With System [NCT04472429]Phase 3308 participants (Actual)Interventional2021-01-12Active, not recruiting
A Phase II Trial Evaluating Feasibility and Quality of Life of Second Look Laparoscopy With HIPEC in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma [NCT04415944]Phase 210 participants (Anticipated)Interventional2021-05-20Recruiting
A Phase III, Open-Label, Randomized Study to Evaluate the Efficacy and Safety of Adjuvant Alectinib Versus Adjuvant Platinum-Based Chemotherapy in Patients With Completely Resected Stage IB (Tumors Equal to or Larger Than 4cm) to Stage IIIA Anaplastic Lym [NCT03456076]Phase 3257 participants (Actual)Interventional2018-08-16Active, not recruiting
A Phase III, Multicenter, Randomized, Placebo-Controlled Study of Atezolizumab (Anti-PD-L1 Antibody) as Monotherapy and in Combination With Platinum-Based Chemotherapy in Patients With Untreated Locally Advanced or Metastatic Urothelial Carcinoma [NCT02807636]Phase 31,213 participants (Actual)Interventional2016-06-30Active, not recruiting
Phase II Open-label Global Study to Evaluate the Effect of Dabrafenib in Combination With Trametinib in Children and Adolescent Patients With BRAF V600 Mutation Positive Low Grade Glioma (LGG) or Relapsed or Refractory High Grade Glioma (HGG) [NCT02684058]Phase 2151 participants (Actual)Interventional2017-12-28Completed
Open Label, Randomised, Parallel Group, Multicentre, Ph III Study To Assess Efficacy, Safety & Tolerability Of Gefitinib (IRESSA™) Versus Carboplatin/Paclitaxel DC As 1st-Line Treatment In Selected Patients With Stage IIIB / IV NSCLC In Asia [NCT00322452]Phase 31,329 participants (Actual)Interventional2006-03-31Completed
Multicenter, Randomized, Open Label Study Evaluating a Poly(ADP-ribose) Polymerase-1(PARP-1) Inhibitor, SAR240550 (BSI-201), Administered Twice Weekly or Weekly, in Combination With Gemcitabine/Carboplatin, in Patients With Metastatic Triple Negative Brea [NCT01045304]Phase 2163 participants (Actual)Interventional2010-02-28Completed
A Phase II Trial Of Neoadjuvant Therapy With Concurrent Chemotherapy And High Dose Radiotherapy Followed By Surgical Resection And Consolidative Therapy For Locally Advanced Non-Small Cell Lung Carcinoma [NCT00096226]Phase 260 participants (Actual)Interventional2004-09-30Completed
A Phase II Study of Carboplatin and Paclitaxel as Neoadjuvant Chemotherapy Followed by Interval Cytoreduction in Women With Advanced Staged Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma for High-Risk Surgical Candidates or Patients U [NCT00331422]Phase 27 participants (Actual)Interventional2005-10-31Terminated(stopped due to Study was terminated due to lack of available funding.)
A Phase II Trial Pemetrexed Carboplatin as First Line Chemotherapy for Advanced Non-Small Cell Lung Cancer (NSCLC) in Elderly Patients [NCT00350792]Phase 262 participants (Actual)Interventional2006-08-31Completed
A Phase I Trial of SS1 (dsFv) PE38 With Paclitaxel, Carboplatin, and Bevacizumab in Subjects With Unresectable Non-Small Cell Lung Adenocarcinoma [NCT01051934]Phase 12 participants (Actual)Interventional2009-12-29Completed
A Study of Unilateral Retinoblastoma With and Without Histopathologic High-Risk Features and the Role of Adjuvant Chemotherapy [NCT00335738]Phase 3331 participants (Actual)Interventional2005-12-31Completed
A Phase 2 Trial of Neoadjuvant Chemoradiation With Pembrolizumab Followed by Pembrolizumab With Lenvatinib in Esophageal/Gastroesophageal Junction Squamous Cell and Adenocarcinomas [NCT04929392]Phase 23 participants (Actual)Interventional2022-01-25Active, not recruiting
A Randomized, Open-label Phase II Study of Pemetrexed (Alimta) Plus Carboplatin With or Without Enzastaurin Hydrochloride, or Docetaxel Plus Carboplatin as First Line Treatment in Patients With Advanced Stage Non-small Cell Lung Cancer (NSCLC) [NCT00308750]Phase 2218 participants (Actual)Interventional2006-03-31Completed
A Phase 1 and 2 Clinical Trial of ALIMTA® (Pemetrexed) in Combination With Carboplatin in Patients With Recurrent Ovarian or Primary Peritoneal Cancer [NCT00489359]Phase 1/Phase 286 participants (Actual)Interventional2005-07-31Completed
A Phase 2 Randomized Study of Tarceva (Erlotinib) as a Single Agent or Intercalated With Combination Chemotherapy in Patients With Newly Diagnosed Advanced Non-small Cell Lung Cancer Who Have Tumors With EGFR Protein Overexpression and/or Increased EGFR G [NCT00294762]Phase 2143 participants (Actual)Interventional2006-01-31Completed
A Phase I/II Trial of Neoadjuvant Paclitaxel, Carboplatin and OSI-774 (Tarceva) With Concurrent Accelerated Hyperfractionation Radiation Followed by Maintenance Therapy With OSI-774 for Stage III Non-Small Cell Lung Cancer [NCT00278148]Phase 1/Phase 232 participants (Actual)Interventional2005-10-31Completed
Treatment of Recurrent or Resistant Pediatric Malignant Germ Cell Tumors With Paclitaxel, Ifosfamide and Carboplatin [NCT00467051]Phase 220 participants (Actual)Interventional2007-11-05Completed
Multicenter, Randomized, Phase II Comparative Study to Compare Efficacy & Safety of Taxotere®/Carboplatin Combination Therapy vs Sequential Therapy w/ Taxotere® Then Carboplatin as Second-line Treatment of Patients w/ Relapsed, Platinum-sensitive Ovarian [NCT00090610]Phase 2150 participants (Actual)Interventional2003-10-31Completed
Study of BAY43-9006 (Sorafenib) in Combination With Carboplatin, Paclitaxel and Bevacizumab in Previously Untreated Patients With Stage IIIB (With Malignant Pleural Effusions) or Stage IV Non-small Cell Lung Cancer (NSCLC) [NCT01069328]Phase 133 participants (Actual)Interventional2006-07-31Completed
A Phase II Study of Fraility Index and Geriatric Assessment as Predictors of Toxicity to Front-Line Chemotherapy in Patients With Stage IV Non-Small Cell Lung Cancer [NCT01026467]45 participants (Actual)Observational2010-01-31Completed
A Phase II Study To Assess The Ability Of Neoadjuvant Chemotherapy Plus/Minus Second Look Surgery To Eliminate All Measurable Disease Prior To Radiotherapy For NGGCT [NCT00047320]Phase 2104 participants (Actual)Interventional2004-01-31Completed
A Phase II Trial of Combination Gemcitabine, Carboplatin With or Without Trastuzumab in Patients With Metastatic Breast Cancer [NCT00193076]Phase 296 participants (Anticipated)Interventional2003-11-30Completed
A Randomized, Phase II Trial of Weekly Paclitaxel, Low-Dose Estramustine, and Carboplatin Administered Either Weekly or Every Four Weeks in the Treatment of Hormone Refractory Prostate Carcinoma [NCT00193193]Phase 2100 participants Interventional2000-08-31Completed
Preoperative (Neoadjuvant) or Postoperative (Adjuvant) Therapy of Patients With Stages IB, II, IIIA Non-Small Cell Lung Cancer [NCT00193310]Phase 2250 participants Interventional2000-11-30Completed
Phase II Evaluation of Gleevec Combined With Camptosar Plus Paraplatin in Patients With Previously Untreated Extensive Stage SCLC [NCT00193349]Phase 260 participants Interventional2002-09-30Completed
Therapeutic Strategy Guided by PET-TDM for Patients With Grade I or Metastatic Seminoma [NCT01887340]Phase 2271 participants (Anticipated)Interventional2013-06-30Recruiting
A Phase 1b Open-Label Study of the Safety and Pharmacokinetics of MEHD7945A in Combination With Either Cisplatin and 5-FU or Paclitaxel and Carboplatin in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT01911598]Phase 124 participants (Actual)Interventional2013-09-19Completed
A Phase II Clinical Trial of Adjuvant Postoperative Irradiation Combined With Paclitaxel/Carboplatin(TP) or Cisplatin/Doxorubicin/Cyclophosphamide (CAP) Chemotherapy for Patients With High-risk Endometrial Cancer [NCT01918124]Phase 280 participants (Anticipated)Interventional2008-01-31Completed
Phase Ib/IIa Study of an Anti-Epidermal Growth Factor Receptor (EGFr) Antibody Cetuximab in Combination With Carboplatin-Paclitaxel in Patients With Chemotherapy-Naive Advanced Non-Small Cell Lung Cancer [NCT00034541]Phase 1/Phase 232 participants (Actual)Interventional2000-12-31Completed
A Phase I Study to Evaluate the Safety and Determine the Maximum Tolerated Dose (MTD) of Debio 1143 Combined With Carboplatin and Paclitaxel in Patients With Squamous Non-Small Cell Lung Cancer (NSCLC), Platinum-refractory Ovarian Cancer, and Basal-like/C [NCT01930292]Phase 131 participants (Actual)Interventional2013-04-30Terminated(stopped due to Part B was cancelled based on business decision)
Phase Ib/II Multicenter Study of Buparlisib Plus Carboplatin or Lomustine in Patients With Recurrent Glioblastoma Multiforme [NCT01934361]Phase 135 participants (Actual)Interventional2014-02-28Completed
Evaluation of TRILACICLIB in Chinese Patients With Extensive-stage Small Cell Lung Cancer (ES-SCLC) for Chemotherapy-induced Myelosuppression, Antitumor Effects of Combination Regimens, and Safety in a Real-world Study [NCT05071703]Phase 430 participants (Actual)Interventional2021-08-11Completed
A Phase II/III, Randomized, Double-Blind, Placebo-Controlled Study of Tiragolumab in Combination With Atezolizumab Plus Pemetrexed and Carboplatin/Cisplatin Versus Pembrolizumab Plus Pemetrexed and Carboplatin/Cisplatin in Patients With Previously Untreat [NCT04619797]Phase 2/Phase 3542 participants (Actual)Interventional2020-12-14Active, not recruiting
NEoadjuvant Chemoradiotherapy for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed (NEEDS Trial) [NCT04460352]Phase 31,020 participants (Anticipated)Interventional2020-11-27Recruiting
A Feasibility Study of De-escalation of Chemotherapy in Patients With Early-Stage HER2 Positive Breast Cancer [NCT04419181]Phase 220 participants (Anticipated)Interventional2024-08-11Suspended(stopped due to Change in the landscape of current treatment of early stage breast cancer. Larger clinical trials answering similar questions are expected to result in the next few years.)
A Randomized, Double-Blind, Phase III Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-407) [NCT03875092]Phase 3125 participants (Actual)Interventional2017-04-21Completed
A Phase 3 Randomized, Placebo-controlled Study to Evaluate the Safety and Efficacy of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) as First-line Intervention in Participants With Metastatic Nonsqu [NCT03829319]Phase 3761 participants (Actual)Interventional2019-03-25Active, not recruiting
Pilot Study of Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer [NCT03121352]Phase 230 participants (Actual)Interventional2017-05-19Completed
A Randomized, Double-Blind, Phase III Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-407) [NCT02775435]Phase 3559 participants (Actual)Interventional2016-06-09Completed
Phase II Trial of Pemetrexed Disodium and Carboplatin in Previously Untreated Extensive Stage Small Cell Lung Cancer [NCT00227565]Phase 250 participants (Actual)Interventional2006-02-28Completed
National, Phase II Study Designed to Evaluate the Safety and Efficacy of Paraplatin in Combination With Taxol in Patients of 70 Years and Older With Ovary Cancer F.I.G.O. Stages III and IV. FAG-2 [NCT00231075]Phase 275 participants Interventional2001-01-31Completed
Phase I Dose Escalation Study of N-Acetylcysteine Administered in Conjunction With Carboplatin, Cyclophosphamide, and Etoposide Phosphate BBBD, in Children With Malignant Brain Tumors [NCT00238173]Phase 12 participants (Actual)Interventional2004-12-31Terminated(stopped due to OHSU IRB closed study to further enrollment 2/17/2006)
Serum Protein Profiling as a Predictor of Gemcitabine Sensitivity in Breast Cancer With Prior Exposure to Anthracyclines and Taxanes [NCT00212069]Phase 230 participants (Anticipated)Interventional2004-03-31Completed
Effect of Platinum-based Versus Non-platinum-based Neoadjuvant Chemotherapy in Triple-negative Breast Cancer [NCT05872412]Phase 282 participants (Anticipated)Interventional2023-06-01Not yet recruiting
A Phase I-II Study of OSI-774 (Tarceva, Erlotinib) With Docetaxel/Carboplatin Followed by Maintenance Therapy With Tarceva as Treatment for Newly Diagnosed Stage III/IV Epithelial Ovarian Cancer, Primary Peritoneal or Fallopian Tube Cancer [NCT00217529]Phase 1/Phase 20 participants Interventional2004-06-30Completed
A Phase II Trial of Docetaxel and Carboplatin for First Relapsed Platinum-Sensitive Stage III and IV Advanced Ovarian Cancer or Peritoneal Carcinoma [NCT00217568]Phase 20 participants Interventional2005-05-31Completed
A Phase II, Open-Label, Multicenter, Prospective Clinical Study to Investigate the Efficacy and Safety of Tislelizumab Combined With Pemetrexed/ Carboplatin in Patients With Brain Metastases of Non-squamous Non-small Cell Lung Cancer [NCT04507217]Phase 236 participants (Actual)Interventional2020-09-15Completed
Phase Ib, IIa Study of Anti-Epidermal Growth Factor Receptor (EGFr) Antibody, Cetuximab, in Combination With Gemcitabine/Carboplatin in Patients With Chemotherapy-Naive Stage IV Non-Small Cell Lung Cancer [NCT01004731]Phase 1/Phase 27 participants (Actual)Interventional2001-06-30Completed
Neoadjuvant Adebrelimab Plus Chemotherapy for Resectable ESCC: a Single Arm, Prospective Phase 2 Clinical Trial [NCT06178211]Phase 236 participants (Anticipated)Interventional2023-12-31Not yet recruiting
A Phase Ⅱ Exploratory Clinical Study of Adebrelimab Combined With Chemotherapy and Concurrent Radiotherapy as First-Line Treatment for Extensive-Stage Oligometastatic Small Cell Lung Cancer [NCT06177925]Phase 262 participants (Anticipated)Interventional2023-12-10Recruiting
A Single-arm，Single Center，Prospective，Phase II Clinical Study of Camrelizumab Combined With Concurrent Chemoradiotherapy for Short-term Postoperative Progression of Head and Neck Squamous Cell Carcinoma [NCT06170697]Phase 246 participants (Anticipated)Interventional2023-03-01Recruiting
A Phase IIIb, Randomized, Multicenter, Open-label Study to Assess the Efficacy of Durvalumab Plus Tremelimumab Versus Pembrolizumab in Combination With Platinum-Based Chemotherapy for First-Line Treatment in Metastatic Non-Small Cell Lung Cancer Patients [NCT06008093]Phase 3280 participants (Anticipated)Interventional2023-12-29Not yet recruiting
A Phase 1/2, First-in-Human Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, MTD/RP2D, and Antitumor Activity of ARTS-021 as a Single Agent and in Combination Therapy in Patients With Solid Tumors [NCT05867251]Phase 1/Phase 2192 participants (Anticipated)Interventional2023-08-30Recruiting
A Randomized, Double-Blind Phase 2/3 Study of Fianlimab (Anti-LAG-3 Antibody), Cemiplimab (Anti-PD-1 Antibody), and Chemotherapy Versus Cemiplimab and Chemotherapy in First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Irresp [NCT05800015]Phase 2/Phase 3950 participants (Anticipated)Interventional2023-08-08Recruiting
An Open-Label, Multinational, Multicenter, Phase IIIb Study With Subcutaneous Administration of Trastuzumab in Patients With HER2-Positive Early Breast Cancer to Evaluate Patient Satisfaction [NCT01964391]Phase 3174 participants (Actual)Interventional2014-02-21Completed
A Phase 2 Platform Study Evaluating the Safety and Efficacy of Novel Treatment Combinations in Patients With Lung Cancer (VELOCITY-Lung) [NCT05633667]Phase 2397 participants (Anticipated)Interventional2023-03-16Recruiting
A Phase 1/2 Study to Evaluate the Safety, Pharmacokinetics, and Efficacy of BLU-222 as a Single Agent and in Combination Therapy for Patients With Advanced Solid Tumors [NCT05252416]Phase 1/Phase 2366 participants (Anticipated)Interventional2022-04-07Recruiting
Pembrolizumab in Combination With R-ICE Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma [NCT05221645]Phase 265 participants (Anticipated)Interventional2022-06-27Recruiting
A Phase I Trial Targeting Mitochondrial Metabolism With Papaverine in Combination With Chemoradiation for Stage II-III Non-Small Cell Lung Cancer [NCT05136846]Phase 128 participants (Anticipated)Interventional2021-12-06Recruiting
A Phase II, Randomized, Open-label Trial of Nivolumab in Combination With Ipilimumab Versus Pemetrexed With Cisplatin or Carboplatin as First-line Therapy for Unresectable Pleural Mesothelioma in Chinese Participants [NCT05136677]Phase 2100 participants (Anticipated)Interventional2022-01-25Recruiting
Phase 2 Study of Two Consequent Chemotherapy Regimens as Induction Preoperative Therapy for Patients With Locally Advanced Triple Negative Breast Cancer [NCT01969032]Phase 241 participants (Actual)Interventional2011-08-31Completed
A Phase II Study Evaluating Efficacy and Safety of Hypomethylating Agent Guadecitabine in Combination With Carboplatin in Extensive Stage Small Cell Lung Cancer [NCT03913455]Phase 224 participants (Actual)Interventional2019-06-06Completed
A Phase II/III Study of Peri-Operative Nivolumab and Ipilimumab in Patients With Locoregional Esophageal and Gastroesophageal Junction Adenocarcinoma [NCT03604991]Phase 2/Phase 3278 participants (Anticipated)Interventional2019-05-03Suspended(stopped due to End of Initial Phase of Multi-phase protocol)
Phase II Trial of Geriatric Evaluation as Selection Criteria and Predictive Factor of Safety in Elderly Patients (≥ 70 Years) With Non-small Cell Lung Cancer (NSCLC)That Can be Treated With Bevacizumab, Carboplatin and Paclitaxel [NCT01980472]Phase 250 participants (Anticipated)Interventional2013-08-31Active, not recruiting
A Pilot Study of Transfusion of rhTPO-Derived Autologous Platelets Cryopreserved With Thrombosol and 2% DMSO in Patients With Gynecologic Malignancy Receiving Carboplatin [NCT00038012]33 participants (Actual)Interventional1999-07-23Completed
A Phase 2 Study of APX005M in Combination With Concurrent Chemoradiation as Neoadjuvant Therapy for Resectable Esophageal and Gastroesophageal Junction Cancers [NCT03165994]Phase 234 participants (Actual)Interventional2017-10-06Completed
Randomized Phase 2 Study of Neoadjuvant Chemotherapy, Carboplatin and Paclitaxel, With or Without Atezolizumab in Triple Negative Breast Cancer (TNBC) [NCT02883062]Phase 267 participants (Actual)Interventional2017-08-02Active, not recruiting
HeadStart4: Newly Diagnosed Children (<10 y/o) With Medulloblastoma and Other CNS Embryonal Tumors Clinical and Molecular Risk-Tailored Intensive and Compressed Induction Chemotherapy Followed by Consolidation With Randomization to Either Single Cycle or [NCT02875314]Phase 4250 participants (Anticipated)Interventional2015-09-30Recruiting
A Phase I/II Clinical Study Evaluating the Safety and Effectiveness of BIO 300 Oral Suspension in Patients Receiving Chemoradiation Therapy for Non-Small Cell Lung Cancer (NSCLC) [NCT02567799]Phase 1/Phase 221 participants (Actual)Interventional2015-11-30Completed
Phase I Dose Escalation of Neoadjuvant Proton Beam Radiotherapy With Concurrent Chemotherapy in Locally Advanced Esophageal Cancer [NCT02213497]Phase 130 participants (Anticipated)Interventional2014-04-30Active, not recruiting
A Phase III Randomised Trial of Peri-Operative Chemotherapy Versus sUrveillance in Upper Tract Urothelial Cancer [NCT01993979]Phase 3261 participants (Actual)Interventional2012-05-31Active, not recruiting
A Phase Ib, Open-Label, Dose-Escalation Study of the Safety and Pharmacology of DNIB0600A in Combination With Carboplatin (With or Without Bevacizumab) in Patients With Platinum-Sensitive Ovarian Cancer or Non-Squamous Non-small Cell Lung Cancer [NCT01995188]Phase 141 participants (Actual)Interventional2013-12-16Completed
Apatinib Mesylate Combined With Albumin Binds Paclitaxel and Carboplatin or Cisplatinum as First-line Treatment for Stage II-IV Epithelial Ovarian Cancer Followed by Apatinib Maintenance Therapy:a Single-arm,Exploratory Clinical Study [NCT04590625]Phase 258 participants (Anticipated)Interventional2020-10-31Recruiting
A Randomized, Open-label Phase III Study of First-line Treatment With Erlotinib Intercalated With Gemcitabine/ Cisplatin or Carboplatin Therapy Versus Erlotinib in Stage IIIB/IV NSCLC Patients With EGFR Mutation [NCT02001896]Phase 360 participants (Anticipated)Interventional2013-12-31Not yet recruiting
A Single Part, Open-Label, Randomised, Three-Way Crossover Study Designed to Evaluate the Pharmacokinetic Parameters and Relative Bioavailability of Sorafenib From Sorafenib (XS005) Tablets and Capsules Compared With Nexavar® (Reference Product) in Health [NCT05967377]Phase 115 participants (Actual)Interventional2018-11-16Completed
A Randomized, Double-blind, Phase 3 Bridging Study Evaluating the Safety and Efficacy of ABP 215 Compared With Bevacizumab in Chinese Subjects With Advanced Non-Squamous Non-Small Cell Lung Cancer [NCT04466917]Phase 30 participants (Actual)Interventional2021-05-15Withdrawn(stopped due to Sponsor decision to early terminate the study)
A Phase II Trial to Correlate Early Clinical Response to Pathologic Outcome With Neoadjuvant Systemic Therapy in Patients With Early Stage Breast Cancer [NCT05020860]Phase 2185 participants (Anticipated)Interventional2023-04-18Recruiting
A Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab Plus Chemotherapy vs Placebo Plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC) [NCT03036488]Phase 31,174 participants (Actual)Interventional2017-03-07Active, not recruiting
A Single-Arm Phase 2 Study to Investigate Bintrafusp Alfa With Platinum-Pemetrexed for TKI-Resistant EGFR-Mutant NSCLC [NCT04971187]Phase 23 participants (Actual)Interventional2021-06-30Terminated(stopped due to PI Request)
A Multicentre Phase II, Open-label, Non-randomized Study Evaluating Platinum-Pemetrexed-Atezolizumab (+/- Bevacizumab) for Patients With Stage IIIB/IV Non-squamous Non-small Cell Lung Cancer With EGFR Mutations, ALK Rearrangement or ROS1 Fusion Progressin [NCT04042558]Phase 2149 participants (Anticipated)Interventional2019-09-26Recruiting
A Phase III, Randomized, Multi-Center, Double-Blind, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With and Following Chemoradiotherapy Compared to Chemoradiotherapy Alone for Treatment in Women With Locally Advanced Cervi [NCT03830866]Phase 3770 participants (Actual)Interventional2019-02-15Completed
A Randomized Phase II Trial of Carboplatin, Paclitaxel, Bevacizumab, With or Without Everolimus for Therapy of Metastatic Malignant Melanoma [NCT00976573]Phase 2149 participants (Actual)Interventional2010-04-30Completed
Neoadjuvant Therapy of PD-1 Blockade Combined With Chemotherapy for Locally Advanced Esophageal Carcinoma [NCT05777707]Phase 1/Phase 289 participants (Anticipated)Interventional2020-10-29Recruiting
A Randomized Phase III Post-operative Trial of Platinum Based Chemotherapy vs. Capecitabine in Patients With Residual Triple-Negative Basal-Like Breast Cancer Following Neoadjuvant Chemotherapy [NCT02445391]Phase 3415 participants (Actual)Interventional2015-10-20Active, not recruiting
Global Study to Assess the Addition of Bevacizumab to Carboplatin and Paclitaxel as Front-line Treatment of Epithelial Ovarian Cancer, Fallopian Tube Carcinoma or Primary Peritoneal Carcinoma [NCT01239732]Phase 31,021 participants (Actual)Interventional2010-12-31Completed
A Phase II Randomized Trial Evaluating the Use of Proton Pump Inhibitors (PPIs) in Conjunction With Chemotherapy, in Patients With Recurrent Unresectable or Metastatic Cancers of the Head and Neck [NCT02013453]Phase 20 participants (Actual)Interventional2013-12-31Withdrawn(stopped due to Lack of funding)
[NCT00051506]Phase 20 participants InterventionalCompleted
A Randomized, Double-Blind, Placebo-Controlled, Study of the Safety and Efficacy of Farletuzumab in Combination With a Platinum-Containing Doublet in Chemotherapy-Naive Subjects With Stage IV Adenocarcinoma of the Lung (FLAIR) [NCT01218516]Phase 2130 participants (Actual)Interventional2011-06-27Completed
A Randomized Phase II Study Evaluating the Activity of Bevacizumab in Combination With Carboplatin Plus Paclitaxel in Patients With Previously Untreated Advanced Mucosal Melanoma [NCT02023710]Phase 2182 participants (Anticipated)Interventional2013-12-31Recruiting
BATTLE-FL: A Biomarker-Integrated Study in Patients With Advanced Non-Small Cell Lung Cancer Treated in the Front-Line (FL) Setting [NCT01263782]Phase 264 participants (Actual)Interventional2011-05-17Completed
A Phase 1b, Single-arm, Open-label Clinical Trial to Evaluate Corrected QT Interval and Drug-drug Interaction of Trastuzumab on Carboplatin in the Presence of Docetaxel in Patients With Metastatic Cancer [NCT00927589]Phase 159 participants (Actual)Interventional2009-07-31Completed
A Phase II Study of Docetaxel and Carboplatin as Second Line Chemotherapy in First Relapse of Platinum Sensitive Epithelial Ovarian Cancer [NCT02026921]Phase 274 participants (Actual)Interventional2004-06-30Completed
PLATI-PARP: A Phase 2 Study of Induction Docetaxel and Carboplatin Followed by Maintenance Rucaparib in Treatment of Patients With Metastatic Castration Resistant Prostate Cancer With Homologous Recombination DNA Repair Deficiency [NCT03442556]Phase 218 participants (Actual)Interventional2018-08-24Active, not recruiting
A Prospective Phase II Trial of Neoadjuvant Systemic Chemotherapy Followed by Extirpative Surgery for Patients With High Grade Upper Tract Urothelial Carcinoma [NCT02412670]Phase 236 participants (Actual)Interventional2015-08-27Completed
Phase II Randomized Study of Taxol (PACLITAXEL), Paraplatin (Carboplatin), and Radiation Therapy for Locally Advanced Inoperable Non-Small Cell Lung Cancer [NCT00006378]Phase 25 participants (Actual)Interventional1999-12-31Completed
A Randomized Phase III Study Comparing Gemcitabine Plus Carboplatin Versus Carboplatin Monotherapy in Patients With Advanced Epithelial Ovarian Carcinoma Who Failed First-Line Platinum-Based Therapy [NCT00006453]Phase 30 participants Interventional1999-09-30Completed
A Randomized Phase III Trial of ICE Chemotherapy With or Without Rituximab for the Treatment of Relapsed or Refractory CD20 Expressing Aggressive B-Cell Non-Hodgkin's Lymphomas in Patients Not Suitable for High Dose Therapy and PBSCT [NCT00006708]Phase 37 participants (Actual)Interventional2000-10-31Terminated(stopped due to lack of accrual)
A Randomized, Double-Blind, Phase III Comparative Trial of 2 Doses of ZD1839 (IRESSA) in Combination With Paclitaxel and Carboplatin Versus Placebo in Combination With Paclitaxel and Carboplatin in Chemotherapy-Naive Patients With Advanced (Stage III or I [NCT00006049]Phase 30 participants Interventional2000-05-31Active, not recruiting
A Phase I Trial of Combination Carboplatin and Lipsomal Doxorubicin (Doxil) In Recurrent Ovarian, Fallopian Tube or Primary Peritoneal Cancer [NCT00006235]Phase 10 participants InterventionalCompleted
A Phase II/III Double Blind Randomized Trial of BMS-275291 vs. Placebo in Patients Receiving Paclitaxel/Carboplatin Chemotherapy for the Treatment of Advanced or Metastatic Non-small Cell Lung Cancer [NCT00006229]Phase 2/Phase 3774 participants (Actual)Interventional2000-04-04Completed
Phase III Multicenter Study in Epithelial Ovarian Carcinoma FIGO Stage IIB-IV Comparing Treatment With Paclitaxel and Carboplatin to Paclitaxel and Carboplatin Sequentially Followed by Topotecan [NCT00006454]Phase 30 participants Interventional1999-12-31Completed
Phase II Trial of Concurrent Paclitaxel, Carboplatin and External Beam Radiotherapy Followed by Surgical Resection in Stage IIIA (N2) Non-small Cell Lung Cancer [NCT00006469]Phase 230 participants (Anticipated)Interventional1999-08-31Completed
Esophageal Cancer: A Phase II Study of Paclitaxel, Carboplatin and 5-Fluorouracil With Simultaneous Radiotherapy Followed by Surgical Resection [NCT00006472]Phase 24 participants (Actual)Interventional2000-01-31Terminated
A Phase 2, Open-label, Multicenter Study Investigating Oncolytic Immunotherapy in Combination With Other Therapy in Patients With Locoregionally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck [NCT05743270]Phase 20 participants (Actual)Interventional2024-01-30Withdrawn(stopped due to Sponsor decision.)
Efficacy and Safety of Tislelizumab With Platinum Doublet Chemotherapy as Neoadjuvant Therapy for Participants With Initially Unresectable Stage III Non-small Cell Lung Cancer: A Single-arm, Phase II Trial [NCT05611879]Phase 230 participants (Anticipated)Interventional2023-03-12Recruiting
A Phase 1 Clinical Study to Evaluate the Bioavailability of Pembrolizumab Via Subcutaneous Injection of MK-3475A, a Formulation of Pembrolizumab With MK-5180, in Participants With Advanced Solid Tumors [NCT05017012]Phase 172 participants (Anticipated)Interventional2021-09-21Recruiting
A Phase II Randomized Trial of Adjuvant Therapy With Pembrolizumab After Resection of Recurrent/Second Primary Head and Neck Squamous Cell Carcinoma With High Risk Features [NCT04671667]Phase 2188 participants (Anticipated)Interventional2021-04-27Recruiting
Integration of Immunotherapy Into Adjuvant Therapy for Resected NSCLC: ALCHEMIST Chemo-IO (ACCIO) [NCT04267848]Phase 31,210 participants (Anticipated)Interventional2020-06-16Recruiting
EA5163/S1709 INSIGNA : A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination With Chemotherapy in Induction/Maintenance or Postprogression in Advanced Nonsquamous Non-Small Cell Lung Cancer (NSCLC) With Immunobiomarker SIGNature [NCT03793179]Phase 3600 participants (Anticipated)Interventional2019-04-05Recruiting
A Phase II Open-Label Study of Sacituzumab Govitecan in Unresectable Locally Advanced/Metastatic Urothelial Cancer [NCT03547973]Phase 2643 participants (Anticipated)Interventional2018-08-13Recruiting
Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trial (ALCHEMIST) [NCT02194738]8,300 participants (Anticipated)Interventional2014-09-26Recruiting
Phase II Toxicity Study of Pleurectomy/Decortication, (Neo) Adjuvant Chemotherapy and Intensity Modulated Radiation Therapy to the Pleura in Patients With Locally Advanced Malignant Pleural Mesothelioma [NCT00715611]Phase 265 participants (Actual)Interventional2008-10-11Active, not recruiting
A Phase II Study of Dose Augmented Rituximab and Ice for Patients With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell Non-Hodgkin's Lymphoma Undergoing Second-Line Therapy Prior to Stem Cell Transplantation [NCT00588094]Phase 220 participants (Actual)Interventional2003-10-31Completed
A Multi-center, Randomized, Double-blinded, Phase III Trial of SHR-1316 or Placebo in Combination With Chemo-radiotherapy in Patients With Limited-stage Small-cell Lung Cancer. [NCT04691063]Phase 3486 participants (Anticipated)Interventional2021-01-22Enrolling by invitation
A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Adjuvant Platinum-Doublet Chemotherapy, With or Without Atezolizumab, in Patients Who Are ctDNA Positive After Complete Surgical Resection of Stage IB to [NCT04611776]Phase 20 participants (Actual)Interventional2021-07-01Withdrawn(stopped due to The positive results from IMpower010 demonstrated benefit by adding atezolizumab as adjuvant therapy in early stage NSCLC. These results raised ethical concerns of enrolling pts to best supportive care over checkpoint inhibition in this setting.)
A Two Arm Phase I Trial of Sorafenib in Combination With Cisplatin/Etoposide or Carboplatin/Pemetrexed in Patients With Solid Tumors [NCT00573690]Phase 131 participants (Actual)Interventional2007-09-30Completed
Paclitaxel Poliglumex (CT-2103)/Carboplatin vs Paclitaxel/Carboplatin for the Treatment of Chemotherapy-Naïve Advanced Non-Small Cell Lung Cancer (NSCLC) in Women With Estradiol > 25 pg/mL [NCT00576225]Phase 30 participants (Actual)Interventional2007-09-30Withdrawn
Almonertinib Plus Pemetrexed and Carboplatin Versus Almonertinib Alone in Advanced NSCLC With EGFR T790M After First- or Second-generation TKIs Therapy: a Randomized, Controlled, Open-label, Phase 2 Study [NCT04592666]Phase 2226 participants (Anticipated)Interventional2020-10-09Not yet recruiting
Dynamic Positron Emission Tomography/Computed Tomography Evaluated the Response of Neoadjuvant Anti-programmed Cell Death Protein 1 Combination With Chemotherapy for Stage Ⅱa-Ⅲb Non-small Cell Lung Cancer [NCT04586465]Phase 223 participants (Anticipated)Interventional2020-10-10Recruiting
Phase III Randomized Trial of Induction Chemotherapy With Gemcitabine and Carboplatin Followed by Elective Paclitaxel Consolidation Versus Paclitaxel and Carboplatin Followed by Elective Paclitaxel Consolidation in Patients With Primary Epithelial Ovarian [NCT00191646]Phase 3919 participants (Actual)Interventional2002-10-31Completed
Phase II Trial of Gemzar Plus Paraplatin (Plus Herceptin in HER2+ Patients) in Metastatic Breast Cancer [NCT00191451]Phase 2150 participants (Actual)Interventional2004-04-30Completed
A Phase II/III Randomized, Double-Blind Study of Paclitaxel Plus Carboplatin in Combination With Vorinostat or Placebo in Patients With Stage IIIB (With Pleural Effusion) or Stage IV Non-Small-Cell Lung Cancer (NSCLC) [NCT00473889]Phase 2/Phase 3253 participants (Actual)Interventional2007-05-31Terminated(stopped due to The study was terminated based on the recommendation by the DSMB following a pre-planned protocol interim analysis because the endpoint was not achieved.)
A Multi-center Phase II Study of Doxil®/Carboplatin in Patients With Advanced or Recurrent Endometrial Carcinoma [NCT00470067]Phase 29 participants (Actual)Interventional2007-02-28Terminated(stopped due to Due to low accrual)
Exploratory Clinical Trial of Sintilimab Combined With Gemcitabine/Carboplatin Regimen in the Treatment of Advanced Primary Pulmonary Lymphoepithelioma-like Carcinoma（LELC） [NCT04312204]Phase 230 participants (Anticipated)Interventional2020-03-31Recruiting
Randomised Phase II Trial of Neoadjuvant Weekly Paclitaxel Plus Carboplatin Compared to Weekly Paclitaxel Alone Followed in Both Arms by Doxorubicin and Cyclophosphamide for Operable or Locally Advanced Basal-like Subtype Breast Cancer Correlating BRCA-1 [NCT00589238]Phase 216 participants (Actual)Interventional2008-01-31Terminated
A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Study to Evaluate the Efficacy and Safety of Toripalimab Injection (JS001) in Combination With Standard Chemotherapy Versus Placebo in Combination With Standard Chemotherapy [NCT04568304]Phase 3364 participants (Anticipated)Interventional2020-11-30Not yet recruiting
A Phase II Study on Treatment De-Intensification in Favorable Squamous Cell Carcinoma of the Oropharynx [NCT01088802]Phase 260 participants (Actual)Interventional2010-03-31Completed
Phase 2 Study of Pemetrexed in Combination With Carboplatin or Cisplatin and Cetuximab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT01087970]Phase 269 participants (Actual)Interventional2010-08-31Completed
A Phase I Study of LBH589 in Combination With Paclitaxel and Carboplatin +/- Bevacizumab the Treatment of Solid Tumors [NCT00556088]Phase 140 participants (Anticipated)Interventional2007-12-31Completed
Randomized Phase 3 Trial of Gemcitabine/Carboplatin With or Without Iniparib (SAR240550) (a PARP1 Inhibitor) in Subjects With Previously Untreated Stage IV Squamous Non-Small-Cell Lung Cancer (NSCLC) [NCT01082549]Phase 3780 participants (Actual)Interventional2010-03-31Completed
Efficacy of Targeted Therapy Combined Chemotherapy in Advanced EGFR Positive NSCLC Patients With Concurrent Driver Gene Mutations [NCT04552613]110 participants (Anticipated)Interventional2020-09-30Recruiting
A Phase II Trial of Weight-based Dosing for Dense Weekly Paclitaxel and Carboplatin in Overweight Patients With a BSA > 2.0 [NCT02756013]Phase 23 participants (Actual)Interventional2016-04-20Terminated(stopped due to Lack of accrual - terminated)
A Window of Opportunity Trial Evaluating the Oral TGF-beta Receptor I Inhibitor Vactosertib in Patients Undergoing Standard of Care Chemoradiotherapy for Locally Advanced Esophageal Adenocarcinoma [NCT06044311]Phase 225 participants (Anticipated)Interventional2023-11-01Not yet recruiting
Phase III Prospective Randomized Trial of Primary Lung Tumor Stereotactic Body Radiation Therapy Followed by Concurrent Mediastinal Chemoradiation for Locally Advanced Non-Small Cell Lung Cancer [NCT05624996]Phase 3474 participants (Anticipated)Interventional2023-05-10Recruiting
A Randomized, Double-blind, Placebo-controlled, Phase 2 Study Evaluating Efficacy and Safety of Inupadenant in Combination With Carboplatin and Pemetrexed in Adults With Nonsquamous Non-small Cell Lung Cancer Who Have Progressed on Immunotherapy [NCT05403385]Phase 2192 participants (Anticipated)Interventional2022-08-26Recruiting
A Phase II Study of Neoadjuvant Sotorasib in Combination With Cisplatin or Carboplatin and Pemetrexed for Surgically Resectable Stage IIA-IIIB Non-Squamous Non-Small Cell Lung Cancer With a KRAS p.G12C Mutation [NCT05118854]Phase 227 participants (Anticipated)Interventional2022-03-30Recruiting
Phase Ib Clinical Study of Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Etoposide and Carboplatin for the First-line Treatment of Patients With Extensive Stage Small Cell Lung Cancer [NCT05116007]Phase 135 participants (Actual)Interventional2021-03-29Active, not recruiting
A Phase 1b Study of ZN-c3 in Combination With Chemotherapy in Patients With Platinum-Resistant Ovarian, Peritoneal or Fallopian Tube Cancer [NCT04516447]Phase 1140 participants (Anticipated)Interventional2020-10-26Recruiting
A Phase 2 Randomized Study of Osimertinib Versus Osimertinib Plus Chemotherapy for Patients With Metastatic EGFR-Mutant Lung Cancers That Have Detectable EGFR-Mutant cfDNA in Plasma After Initiation of Osimertinib [NCT04410796]Phase 2571 participants (Anticipated)Interventional2020-05-28Recruiting
Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer [NCT03801876]Phase 3300 participants (Anticipated)Interventional2019-03-15Recruiting
A Phase I/II Study of Paclitaxel Plus Carboplatin and Durvalumab (MEDI4736) With or Without Oleclumab (MEDI9447) for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer [NCT03616886]Phase 1/Phase 2129 participants (Actual)Interventional2018-12-28Active, not recruiting
Phase III Study Comparing Neoadjuvant Chemotherapy With Carboplatin and Paclitaxel Followed by Standard Therapy, With Standard Therapy Alone in Women With Cervical Cancer and Para Aortic Positive Lymph Node. [NCT03534713]Phase 3310 participants (Anticipated)Interventional2020-07-17Recruiting
A Phase III, Randomized, Placebo-controlled, Double-blind, Multi-center, International Study of Durvalumab Given Concurrently With Platinum-based Chemoradiation Therapy in Patients With Locally Advanced, Unresectable NSCLC (Stage III) (PACIFIC2) [NCT03519971]Phase 3328 participants (Actual)Interventional2018-03-29Active, not recruiting
A Phase III, Randomised, Open-label, Multicentre, Global Study of Datopotamab Deruxtecan (Dato-DXd) in Combination With Durvalumab and Carboplatin Versus Pembrolizumab in Combination With Platinum-based Chemotherapy for the First-line Treatment of Patient [NCT05687266]Phase 31,000 participants (Anticipated)Interventional2022-12-29Recruiting
Open-label, Prospective Phase III Clinical Study to Compare Polatuzumab Vedotin Plus Rituximab, Ifosfamide, Carboplatin and Etoposide (Pola-R-ICE) With Rituximab, Ifosfamide, Carboplatin and Etoposide (R-ICE) Alone as Salvage Therapy in Patients With Prim [NCT04833114]Phase 3334 participants (Anticipated)Interventional2021-04-30Recruiting
Phase I Trial With Expansion Cohort of OBP-301 (Telomelysin™) and Definitive Chemoradiation for Patients With Locally Advanced Esophageal and Gastroesophageal Cancer Who Are Not Candidates for Surgery [NCT04391049]Phase 116 participants (Anticipated)Interventional2020-06-29Recruiting
A Dynamic Allocation Modular Sequential Trial of Approved and Promising Therapies in Men With Metastatic Castrate Resistant Prostate Cancer [NCT02703623]Phase 2196 participants (Actual)Interventional2016-05-18Active, not recruiting
A Randomized Phase II Study of Neoadjuvant Carboplatin/Paclitaxel (CT) Versus Panitumumab/Carboplatin/Paclitaxel (PaCT) Followed by Anthracycline-Containing Regimen for Newly Diagnosed Primary Triple-Negative Inflammatory Breast Cancer [NCT02876107]Phase 242 participants (Actual)Interventional2016-10-06Active, not recruiting
An Open Label, Randomized, Two Arm Phase III Study of Nivolumab in Combination With Ipilimumab Versus Extreme Study Regimen (Cetuximab + Cisplatin/Carboplatin + Fluorouracil) as First Line Therapy in Recurrent or Metastatic Squamous Cell Carcinoma of the [NCT02741570]Phase 3947 participants (Actual)Interventional2016-10-05Completed
ENGOT-EN1/FANDANGO: A Randomized Phase II Trial of First-line Combination Chemotherapy With Nintedanib / Placebo for Patients With Advanced or Recurrent Endometrial Cancer [NCT02730416]Phase 2146 participants (Actual)Interventional2016-12-12Completed
A Randomized, Phase II Study Evaluating MK-1775 in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Adult Patients With Platinum Sensitive p53 Mutant Ovarian Cancer [NCT01357161]Phase 2136 participants (Actual)Interventional2011-07-26Completed
Phase II Trial of Induction Therapy With Docetaxel, Cisplatin and Fluorouracil in Previously Untreated Patients With Locally Advanced Squamous Cell Carcinoma and/or Poorly Differentiated Carcinoma of the Nasal Cavity and/or Paranasal Sinuses [NCT00707473]Phase 231 participants (Actual)Interventional2008-06-16Active, not recruiting
CSMC IIT: Pilot Study of Phosphodiesterase-V Inhibition to Increase Intratumoral Concentration of Carboplatin in Patients With Recurrent High Grade Gliomas and Brain Metastases [NCT02279992]Early Phase 17 participants (Actual)Interventional2012-03-27Terminated(stopped due to Unable to accrue to the study. Original PI no longer with the institute.)
A Phase I Dose Escalation Study Evaluating MK-1775 in Both Monotherapy and in Combination With Either Gemcitabine, Cisplatin, or Carboplatin in Adult Subjects With Advanced Solid Tumors [NCT00648648]Phase 1206 participants (Actual)Interventional2008-02-25Completed
An Early Phase Randomized Trial of APX005M in BRCAwt Patients With Recurrent Ovarian Cancer [NCT05201001]Phase 20 participants (Actual)Interventional2023-09-07Withdrawn(stopped due to IMP provider company (Apexigen) is sold, thus both IMP and grant is terminated)
Phase II Trial of Weekly Carboplatin-Paclitaxel Adjuvant Chemotherapy After Intensity Modulated Extended-field Chemoradiation in the Treatment of Locally Advanced Cervical Cancer With Para-aortic Positive Nodes [NCT04016142]Phase 221 participants (Actual)Interventional2020-07-15Active, not recruiting
Phase 2 Open Label Study of Durvalumab With Neoadjuvant Chemotherapy in Variant Histology Bladder Cancer [NCT03912818]Phase 27 participants (Actual)Interventional2019-04-10Terminated(stopped due to Difficulty with enrollment)
A Randomized Phase II Study to Evaluate the Efficacy and Safety of Chemotherapy (CT) vs Androgen Deprivation Therapy (ADT) in Patients With Recurrent and/or Metastatic, Androgen Receptor (AR) Expressing, Salivary Gland Cancer (SGCs) [NCT01969578]Phase 2149 participants (Actual)Interventional2015-09-24Active, not recruiting
Phase I Study of Flavopiridol in Combination With Cisplatin in Patients With Advanced Malignancies [NCT00003690]Phase 148 participants (Anticipated)Interventional1998-12-31Completed
[NCT01648517]Phase 260 participants (Actual)Interventional2012-07-27Completed
IClyCO Influence of Chemotherapy (Carboplatin and Taxol) on the ex Vivo Expansion and Functional Capacity of Gamma-delta T Cells in Patients With Epithelial Ovarian Cancer [NCT01606358]0 participants (Actual)ObservationalWithdrawn
Ixazomib (MLN9708) in Combination With Carboplatin in Pretreated Women With Advanced Triple Negative Breast Cancer [NCT02993094]Phase 1/Phase 231 participants (Actual)Interventional2016-11-21Terminated(stopped due to Due to slow recruitment, the study had to be terminated prematurely.)
AVF3963s Neoadjuvant Bevacizumab and Carboplatin Followed by Concurrent Bevacizumab, Carboplatin and Radiotherapy in the Primary Treatment of Cervix Cancer [NCT00600210]Phase 20 participants (Actual)Interventional2008-01-31Withdrawn(stopped due to low patient accrual)
A Multi-centric, Open-label, Phase II Study Investigating the Combination of Afinitor With Paclitaxel and Carboplatin in First Line Treatment of Patients With Advanced (Stage IV) Large Cell Lung Cancer With Neuroendocrine Differentiation (LC-NEC) [NCT01317615]Phase 449 participants (Actual)Interventional2011-04-30Completed
Phase II Trial of Abraxane Plus Carboplatin for Advanced NSCLC for Patients at Risk of Bleeding From VEGF Directed Therapies [NCT00729612]Phase 263 participants (Actual)Interventional2008-08-14Completed
A Phase I/II Pharmacokinetic and Pharmacodynamic Study of ABT-751 in Combination With Carboplatin in Patients With Advanced Lung Cancer [NCT00735878]Phase 1/Phase 220 participants (Actual)Interventional2004-09-30Terminated(stopped due to data from a similar did not show efficacy.)
A Phase II Randomized Clinical Trial of Neo-adjuvant Weekly Paclitaxel With or Without Carboplatin in Early Breast Cancer [NCT00919880]Phase 2148 participants (Actual)Interventional2009-07-31Completed
Effects of Chemotherapy on Brain Structure and Function [NCT00755313]81 participants (Actual)Observational2007-05-31Completed
Tandem High-dose Chemotherapy and Autologous Stem Cell Rescue in Patients With High-risk Neuroblastoma [NCT00793845]Phase 240 participants (Anticipated)Interventional2008-08-31Completed
Albumin Bound (Nab)-Paclitaxel Combined With Carboplatin Versus Paclitaxel Combined With Carboplatin Followed by Epirubicin and Cyclophosphamide as Neoadjuvant Treatment for Participants With Triple Negative Breast Cancer (TNBC) [NCT04067102]0 participants (Actual)Interventional2019-05-10Withdrawn(stopped due to No patients recruited)
A Randomized, Multicenter, Open Label, Phase I/II Study to Evaluate the Safety, Clinical and Biological Activity of a Humanized Monoclonal Antibody Targeting Netrin-1 (NP137) in Combination With Carboplatin Plus Paclitaxel and/or Pembrolizumab in Patients [NCT04652076]Phase 1/Phase 2240 participants (Anticipated)Interventional2020-12-14Recruiting
Phase II Study of Induction Checkpoint Blockade for Untreated Stage I-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection [NCT03158129]Phase 2101 participants (Actual)Interventional2017-06-09Active, not recruiting
Phase IB Study to Evaluate the Safety of Selinexor (KPT-330) in Combination With Multiple Standard Chemotherapy or Immunotherapy Agents in Patients With Advanced Malignancies [NCT02419495]Phase 1221 participants (Actual)Interventional2015-06-26Active, not recruiting
Conservative Treatments of Retinoblastoma [NCT02866136]Phase 2133 participants (Anticipated)Interventional2012-02-29Active, not recruiting
Phase I/Ib First-in-Human Study of EOS100850 as a Single Agent and in Combination With Pembrolizumab and/or Chemotherapy in Participants With Advanced Cancers [NCT03873883]Phase 1119 participants (Actual)Interventional2019-01-28Active, not recruiting
A Pilot Phase II Trial of Intravenous Paclitaxel and Intraperitoneal Carboplatin/Taxol Followed by Radiation in Patients With Advanced Stage Uterine Serous Carcinoma [NCT04030000]Phase 1/Phase 20 participants (Actual)Interventional2020-05-20Withdrawn(stopped due to could not enroll anyone due to staff changes)
A Phase II Trial Comparing Quality of Life After HIPEC in Patients With Stage IIIC and IV Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma [NCT03188432]Phase 250 participants (Actual)Interventional2017-10-13Active, not recruiting
ROCKIF Trial: Re-sensitization of Carboplatin-resistant Ovarian Cancer With Kinase Inhibition of FAK [NCT03287271]Phase 1/Phase 290 participants (Anticipated)Interventional2018-02-06Recruiting
Multi-Center, Open-Label Phase 1B Study to Evaluate the Safety and Tolerability of HGS1036 in Combination With Paclitaxel and Carboplatin, Cisplatin and Etoposide, or Docetaxel in Subjects With Advanced Solid Malignancies [NCT01604863]Phase 154 participants (Anticipated)Interventional2012-06-30Suspended(stopped due to Study suspended prior to enrollment)
An Open Labeled, Multicentre, Randomized Phase II Trial of Combination Gemcitabine and Carboplatin Chemotherapy in Patients With Metastatic or Recurrent Nasopharyngeal Carcinoma [NCT00697905]Phase 218 participants (Actual)Interventional2008-01-31Completed
A Phase II Trial of Carboplatin, Ixabepilone and Cetuximab in Chemotherapy Naive Advanced Non-Small Cell Lung Cancer [NCT00998101]Phase 20 participants (Actual)Interventional2009-07-31Withdrawn(stopped due to Study was withdrawn due issuses related to the science)
Randomized, Open Label, Stratified Phase 2 Trial of Gemcitabine, Carboplatin, and Cetuximab With Vs. Without IMC-A12 in Chemotherapy-Naive Patients With Advanced/Metastatic Non-Small Cell Lung Cancer [NCT00870870]Phase 264 participants (Actual)Interventional2009-03-31Completed
The Effect of Pharmacogenetics on Treatment Toxicities and Outcomes in East Asian and Caucasian Patients Undergoing Docetaxel or Gemcitabine-based Chemotherapy [NCT00695994]Phase 2300 participants (Actual)Interventional2006-10-31Completed
A Randomized Phase III Double-Blind Placebo-Controlled Trial of First-Line Chemotherapy and Trastuzumab With or Without Bevacizumab for Patients With HER-2/NEU Over-Expressing Metastatic Breast Cancer [NCT00520975]Phase 396 participants (Actual)Interventional2007-11-30Terminated(stopped due to Closed early due to slow accrual)
Clinical Study of Nab-paclitaxel Plus Carboplatin Versus Nab-paclitaxel Plus Capecitabine in the Treatment of Advanced Triple-negative Breast Cancer [NCT04159142]Phase 2414 participants (Anticipated)Interventional2019-11-20Recruiting
A Phase 1b Trial to Evaluate the Safety and Pharmacokinetics of Volociximab (M200) in Combination With Carboplatin and Paclitaxel in Subjects With Previously Untreated Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC) [NCT00654758]Phase 133 participants (Actual)Interventional2007-12-31Completed
A Phase II Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer [NCT00660140]Phase 249 participants (Actual)Interventional2002-03-31Completed
Phase II Trial of Preoperative (Neo-adjuvant) Therapy in Patients With Stages IB, II, IIIA, and Selected IIIB Patients With Non-Small Cell Lung Cancer [NCT00193427]Phase 275 participants (Actual)Interventional2004-04-30Completed
Phase 1b Trial Evaluating the Safety of Volociximab in Combination With Carboplatin, Paclitaxel, and Bevacizumab in Subjects With Previously Untreated Stage IIIB/IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC) [NCT00666692]Phase 17 participants (Actual)Interventional2008-04-30Completed
Phase I/IIa Study of the Novel Combination of Bendamustine With Irinotecan Followed by Etoposide/Carboplatin in Chemonaive Patients With Extensive Stage Small Cell Lung Cancer [NCT00856830]Phase 1/Phase 230 participants (Actual)Interventional2009-04-30Completed
A Phase II, Multinational and Multicenter, Randomized, Controlled Study of Paclitaxel and Carboplatin With vs Without Nitroglycerin in Patients With Untreated Advanced Non-small Cell Lung Cancer [NCT00616031]Phase 2150 participants (Anticipated)Interventional2008-01-31Recruiting
A Trial of Neoadjuvant Chemotherapy Followed by Surgery Versus Surgery in FIGO IB2 and IIA2 Cervical Cancer(CSEM005) [NCT02629718]Phase 3700 participants (Anticipated)Interventional2015-12-31Recruiting
A Phase 1 Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of GEN1042 Monotherapy and in Combination With Pembrolizumab ± Chemotherapy in Japanese Subjects With Malignant Solid Tumors [NCT06057038]Phase 130 participants (Anticipated)Interventional2023-10-31Recruiting
An Open-label Phase 1/2 Dose Finding, Safety and Efficacy Study of Oral NEO212 in Patients With Astrocytoma IDH-mutant, Glioblastoma IDH-wildtype or Uncontrolled Brain Metastasis in Patients With Select Solid Tumors. [NCT06047379]Phase 1/Phase 2134 participants (Anticipated)Interventional2023-11-01Recruiting
Response-based Treatment of High-risk Neuroblastoma [NCT02771743]Phase 254 participants (Anticipated)Interventional2015-04-30Recruiting
A Phase III Clinical Trial of Bevacizumab With IV Versus IP Chemotherapy in Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma [NCT00951496]Phase 31,560 participants (Actual)Interventional2009-08-11Completed
A Phase II Evaluation of Belinostat (NSC #726630) and Carboplatin (NSC #241240) in the Treatment of Recurrent or Persistent Platinum-Resistant Ovarian, Fallopian Tube, or Primary Peritoneal Cancer [NCT00993616]Phase 229 participants (Actual)Interventional2009-12-31Completed
Dose Finding Phase 1 Study of the Treatment of Recurrent/Relapsed Glioblastoma Multiforme With MPC-6827 in Combination With Carboplatin [NCT00635557]Phase 1/Phase 230 participants (Anticipated)Interventional2008-03-31Active, not recruiting
Phase 1/2 Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer [NCT02735239]Phase 1/Phase 273 participants (Actual)Interventional2016-06-24Completed
Impact of Fat-free Mass in the Carboplatin Calculated Dose and Chemotherapeutic Toxicity in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT02734069]132 participants (Anticipated)Observational2016-02-29Recruiting
A Phase II, Multicentre, Randomised Trial Comparing Combination Gemcitabine/Carboplatin and Hydroxychloroquine Versus Carboplatin/Etoposide Therapy Alone in Small Cell Lung Cancer (SCLC) [NCT02722369]Phase 272 participants (Actual)Interventional2017-03-14Terminated(stopped due to Low recruitment, lack of efficacy and increased adverse events in investigational arm.)
A Phase 1 Trial of MK-7684 as Monotherapy and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors [NCT02964013]Phase 1492 participants (Anticipated)Interventional2016-12-13Active, not recruiting
Phase II Study of Pembrolizumab in Combination With Carboplatin and Paclitaxel for Advanced or Recurrent Endometrial Adenocarcinoma [NCT02549209]Phase 246 participants (Actual)Interventional2017-08-22Completed
A Multi Centre, Pilot Phase II Trial Assessing the Efficacy and Safety of Bevacizumab + Gemcitabine + Carboplatin as First Line Treatment for Patients Diagnosed With Triple Negative Metastatic Breast Cancer [NCT01201265]Phase 240 participants (Actual)Interventional2011-02-28Completed
A Randomized Phase II Study to Evaluate Efficacy and Safety of DCVAC/LuCa Added to Chemotherapy With Carboplatin and Pemetrexed vs Chemotherapy Alone in Patients With Stage IV Non-small Cell Lung Cancer [NCT02669719]Phase 270 participants (Anticipated)Interventional2016-01-31Recruiting
Phase Ib/II Study of Combination of Vorinostat, Carboplatin and Gemcitabine + Vorinostat Maintenance in Women With Recurrent, Platinum-Sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer [NCT00910000]Phase 1/Phase 215 participants (Actual)Interventional2009-06-30Terminated(stopped due to Terminated due to unacceptable toxicity)
A Phase II Safety and Efficacy Study of Bavituximab Plus Paclitaxel and Carboplatin in Patients With Previously Untreated Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00687817]Phase 249 participants (Actual)Interventional2008-06-30Completed
A Non-interventional Study of Nab-paclitaxel (Abraxane®) in Combination With Carboplatin as First Line Therapy in Patients With Advanced Non-small Cell Lung Cancer (NEPTUN) [NCT02799862]408 participants (Actual)Observational2016-08-29Completed
Study of Predictive Factors of Chemoresistance in Ovarian Cancer [NCT02878122]13 participants (Actual)Observational2015-03-31Completed
Clinical Study of Hydrochloride Anlotinib Combined With Concurrent Radiochemotherapy for Locally Advanced (Stage IB3 and IIA2-IVA) Cervical Cancer [NCT04772001]53 participants (Anticipated)Interventional2021-03-12Recruiting
A Phase I/II Trial of Epirubicin, Carboplatin & Capecitabine in Adult Cancer Patients [NCT00021047]Phase 1/Phase 20 participants Interventional2001-07-31Completed
Phase 1, Dose Escalation Study of CP-751,871 in Combination With Carboplatin and Paclitaxel in Previously Untreated Patients With Advanced Non-Small Cell Lung Cancer [NCT00603538]Phase 119 participants (Actual)Interventional2008-01-31Completed
Phase II Trial of Carboplatin and Bevacizumab for Progressive Breast Cancer Brain Metastases [NCT01004172]Phase 238 participants (Actual)Interventional2009-11-30Completed
A Two Arm Phase II Trial of Sequential Axitinib and Carboplatin/Paclitaxel in Melanoma With Correlative FLT PET Scans (3'Deoxy-3'-18F-Fluorothymidine Positron Emission Tomography Scans)(CC# 10852) [NCT01174238]Phase 240 participants (Actual)Interventional2010-07-31Completed
Phase I Study of Panobinostat Plus ICE Chemotherapy Followed by a Randomized Phase-II Study of ICE Compared With Panobinostat Plus ICE for Patients With Relapsed and Refractory Classical Hodgkin Lymphoma [NCT01169636]Phase 1/Phase 262 participants (Actual)Interventional2011-01-31Completed
A Phase Ib Study to Evaluate the Safety and Tolerability of Durvalumab and Tremelimumab in Combination With First-Line Chemotherapy in Patients With Advanced Solid Tumors. [NCT02658214]Phase 132 participants (Actual)Interventional2016-04-28Completed
Tocotrienol as a Nutritional Supplement in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) [NCT02644252]Phase 379 participants (Actual)Interventional2016-01-31Terminated(stopped due to The trial was ended prematurely because of a poor accrual rate)
Efficacy, Safety & Immunogenicity Study of CBT124 & EU-sourced Avastin® in Combination With Carboplatin and Paclitaxel in First-line Treatment in (NSCLC) [NCT02879097]Phase 3200 participants (Anticipated)Interventional2016-12-31Not yet recruiting
Phase II Trial of Neoadjuvant Anti-PD-1 Antibody (Toripalimab) or Combined With Chemotherapy in Head and Neck Squamous Cell Carcinoma Patients [NCT04164238]Phase 290 participants (Anticipated)Interventional2019-11-07Recruiting
Phase II Study of Genasense-Carboplatin-Paclitaxel-Combination in Uveal Melanoma [NCT01200342]Phase 27 participants (Actual)Interventional2010-12-31Terminated(stopped due to Pharmaceutical company no longer manufacturing investigational product.)
Open-label Study of Bevacizumab (Avastin®) in Combination With Pemetrexed or Pemetrexed and Carboplatin as First-line Treatment of Patients With Advanced or Recurrent Non-squamous Non-small Cell Lung Cancer [NCT00976456]Phase 3271 participants (Actual)Interventional2009-09-30Completed
Safety and Feasibility of Irradiation and Nivolumab in Esophageal Cancer (INEC-study) - a Phase I/II Trial [NCT03544736]Phase 1/Phase 230 participants (Anticipated)Interventional2018-04-26Active, not recruiting
A Randomized Phase II Study of S1 Plus Carboplatin Followed by Maintenance S1versus Pemetrexed Plus Carboplatin Followed by Maintenance Pemetrexed in Patients With EGFR Wild Type Stage IIIB or IV Nonsquamous Non-Small-Cell Lung Cancer [NCT02631460]Phase 2470 participants (Anticipated)Interventional2015-12-31Recruiting
Randomized, Open Label, Phase III Trial Of CP- 751,871 In Combination With Paclitaxel And Carboplatin Versus Paclitaxel And Carboplatin In Patients With Non Small Cell Lung Cancer [NCT00596830]Phase 3681 participants (Actual)Interventional2008-04-30Terminated(stopped due to See termination reason in detailed description.)
Treatment Intensification With R-ICE and High-Dose Cyclophosphamide for Diffuse Large B-Cell Non-Hodgkin's Lymphoma Based on Early [18F] FDG-PET Scanning [NCT00809341]Phase 227 participants (Actual)Interventional2009-01-31Terminated(stopped due to Low accrual)
Multicentre Randomised Phase II Trial of Erlotinib Versus Carboplatin/Vinorelbine in Elderly Patients (=/> 70 Years) With Advanced Non-Small Cell Lung Cancer [NCT00678964]Phase 2260 participants (Anticipated)Interventional2006-06-30Recruiting
ProBio: An Outcome-adaptive and Randomized Multi-arm Biomarker Driven Study in Patients With Metastatic Prostate Cancer [NCT03903835]Phase 3750 participants (Anticipated)Interventional2019-02-01Recruiting
Open-label, Single-arm, Multicenter, Phase II Study Investigating Cetuximab in Combination With Chemotherapy in the First-line Treatment of Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) in Japanese Subjects [NCT00971932]Phase 233 participants (Actual)Interventional2009-07-31Completed
Department of Radiation, Sun Yat-sen University [NCT05367206]Phase 3280 participants (Anticipated)Interventional2022-03-14Recruiting
A Phase II Trial of Intravenous Gemcitabine (NSC #613327) and Intraperitoneal Carboplatin (NSC # 241240) in the Treatment of Patients With Platinum-Sensitive Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma With Non-Measurable Disease [NCT00369954]Phase 20 participants (Actual)Interventional2006-04-30Withdrawn(stopped due to Trial was never activated)
Phase I Dose-Escalating, Open-Label, Non-Placebo Controlled Study of BAY 43-9006 (Sorafenib) in Combination With Carboplatin, Paclitaxel and Bevacizumab in Previously Untreated Patients With Stage IIIB (With Malignant Pleural Effusions) or Stage IV Non-Sm [NCT00533585]Phase 123 participants (Actual)Interventional2006-05-31Completed
Phase I/II Trial Of Temozolomide And Carboplatin In Recurrent Glioblastoma Multiforme [NCT00021307]Phase 1/Phase 20 participants (Actual)InterventionalWithdrawn(stopped due to Study not activated.)
Phase II Randomized Controlled Trial of Neoadjuvant Pembrolizumab or Pembrolizumab With Histology-Specific Chemotherapy for Operable Stage IA3 to IIA Non-Small Cell Lung Cancer (NSCLC) [NCT04638582]Phase 244 participants (Anticipated)Interventional2022-08-28Recruiting
A Multicentre Randomised Phase III Trial Comparing Atezolizumab Plus Bevacizumab and Standard Chemotherapy Versus Bevacizumab and Standard Chemotherapy as First-line Treatment for Advanced Malignant Pleural Mesothelioma [NCT03762018]Phase 3401 participants (Actual)Interventional2019-04-30Active, not recruiting
Precise Treatment for BLIS Subtype of Triple-negative Breast Cancer in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer [NCT05806060]Phase 3192 participants (Anticipated)Interventional2023-04-25Recruiting
A Phase III Trial of Adjuvant Chemotherapy Following Chemoradiation as Primary Treatment for Locally Advanced Cervical Cancer Compared to Chemoradiation Alone: The OUTBACK Trial [NCT01414608]Phase 3926 participants (Actual)Interventional2012-01-09Completed
A Phase I Study of Premetrexed (Alimta) and Carboplatin and Radiation Therapy in Patients With Inoperable Non Small Cell Lung Cancer. [NCT00330044]Phase 118 participants (Actual)Interventional2006-04-30Completed
Sequential Administration of Docetaxel/Gemcitabine Followed by Concurrent Chemo-radiotherapy, With or Without Consolidation Chemotherapy, as First Line Treatment in Patients With Unresectable Stage IIIA/IIIB NSCLC. A Randomized Phase II Study [NCT00431613]Phase 238 participants (Actual)Interventional2006-03-31Terminated(stopped due to Due to Poor Accrual)
Phase II Study of Radiation Followed by Paclitaxel, Carboplatin, and Bevacizumab (PCA) in Patients With Stage IIIB and IV Squamous Non-Small Cell Lung Cancer [NCT00334763]Phase 232 participants (Anticipated)Interventional2006-05-31Terminated(stopped due to Principal Investigator felt risk to patients was too high.)
An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors [NCT01419548]Phase 10 participants (Actual)Interventional2011-07-29Withdrawn
[NCT00162695]Phase 3400 participants Interventional1995-07-31Terminated
SIOP CNS GCT II: Prospective Trial for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Intracranial Germ Cell Tumors [NCT01424839]Phase 4400 participants (Anticipated)Interventional2011-10-31Recruiting
A Phase I/II Study of Nal-IRI (ONIVYDE® ) and Carboplatin in Patients With Advanced or Metastatic Gastroenteropancreatic Poorly Differentiated Neuroendocrine Carcinoma [NCT05385861]Phase 1/Phase 252 participants (Anticipated)Interventional2022-07-01Not yet recruiting
Prediction for pCR After Neoadjuvant Immunotherapy Combined With Chemotherapy Using Single-Cell RNA Sequencing in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC) : A Single-Arm Phase II Clinical Trial [NCT05807542]Phase 220 participants (Anticipated)Interventional2022-03-01Recruiting
A Randomized Phase II Trial Investigating the Addition of Carboplatin to Neoadjuvant Therapy for Triple-negative and HER2-positive Early Breast Cancer [NCT01426880]Phase 2/Phase 3595 participants (Actual)Interventional2011-08-31Completed
Multicenter, Randomized, Open-label Phase II Study to Compare the Efficacy and Safety of Trastuzumab and Paclitaxel Based Regimen Plus Carboplatin or Epirubicin as Neoadjuvant Therapy in HER2-positive Breast Cancer Patients [NCT01428414]Phase 2100 participants (Anticipated)Interventional2011-08-31Active, not recruiting
Randomized Phase II/III Study of Individualized Neoadjuvant Chemotherapy in ' Triple Negative' Breast Tumors [NCT01057069]Phase 2/Phase 3310 participants (Actual)Interventional2010-01-31Active, not recruiting
INST: Phase I-II Study of Carboplatin, Vinorelbine and Capecitabine in Patients With Metastatic Breast Cancer [NCT00277069]Phase 1/Phase 233 participants (Actual)Interventional2000-05-31Completed
Germ Cell Tumour Study II [NCT00276718]100 participants (Anticipated)Interventional1989-04-30Active, not recruiting
Cooperative Multicenter Study for Children and Adolescents With Low Grade Glioma [NCT00276640]3,417 participants (Actual)Interventional2004-04-01Completed
A Randomized, Open-label Study of Serplulimab Plus Chemotherapy (Carboplatin-Etoposide) in Comparison With Atezolizumab Plus Chemotherapy in Previously Untreated US Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) (ASTRIDE) [NCT05468489]Phase 3200 participants (Anticipated)Interventional2022-11-18Recruiting
A Phase 3 Randomized Study of Selumetinib Versus Carboplatin/Vincristine in Newly Diagnosed or Previously Untreated Neurofibromatosis Type 1 (NF1) Associated Low-Grade Glioma (LGG) [NCT03871257]Phase 3290 participants (Anticipated)Interventional2020-01-15Recruiting
A Phase I/II Trial of Induction Chemotherapy Plus Gefitinib (Iressa) Followed by Concurrent Chemotherapy, Radiation Therapy, and Gefitinib (Iressa) For Patients With Locally Advanced Squamous Carcinoma of the Head and Neck [NCT00193284]Phase 250 participants Interventional2003-10-31Completed
Phase III Randomized Study of Paclitaxel, Carboplatin, and Gemcitabine Versus Gemcitabine and Vinorelbine as First-Line Chemotherapy for Stage IIIB and IV Non-Small Cell Lung Cancer [NCT00193362]Phase 3200 participants Interventional2004-06-30Completed
A Randomized, Phase II Trial of Weekly Taxol (Paclitaxel) Versus Weekly Taxol Plus Paraplatin (Carboplatin) as First-Line Chemotherapy in Patients Age 65 Years or Older With Metastatic Breast Cancer [NCT00025688]Phase 30 participants Interventional2001-01-31Active, not recruiting
Phase II Selection Design Trial Of Concurrent Chemotherapy + Cetuximab Vs. Chemotherapy Followed By Cetuximab In Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00085501]Phase 2242 participants (Actual)Interventional2004-07-31Completed
Phase I Study of BMS-188797 in Combination With Carboplatin in Patients With Advanced Malignancies [NCT00006086]Phase 10 participants Interventional2000-06-30Completed
A Phase I/II Study of G3139 (Genasense) in Combination With RICE Chemotherapy in Relapsed B-Cell Non-Hodgkin's Lymphoma [NCT00086944]Phase 1/Phase 225 participants (Actual)Interventional2004-05-31Completed
A Phase III Randomized Trial of Gemcitabine/Oxaliplatin (GEMOX) Versus Carboplatin/Paclitaxel (CP) as First-Line Therapy in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00087802]Phase 3383 participants (Actual)Interventional2004-03-31Completed
Phase II Study of the Combination of Bevacizumab Plus Pemetrexed and Carboplatin as First-line Therapy in Patients With Malignant Pleural Mesothelioma [NCT00407459]Phase 277 participants (Actual)Interventional2007-09-30Completed
A Phase I Study of SU5416, an Antiangiogenesis Agent, in Combination With Carboplatin in Patients With Platinum-Refractory Ovarian Cancer [NCT00006155]Phase 133 participants Interventional2000-08-31Completed
A Pilot Trial of a CEA/TRICOM-Based Vaccine in Combination With Combined Chemotherapy/Radiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC) [NCT00091039]0 participants Interventional2004-08-31Completed
A Phase 2 Trial of Pharmacological Ascorbate With Concurrent Chemotherapy and Radiation Therapy for Non-small Cell Lung Cancer [NCT02905591]Phase 246 participants (Anticipated)Interventional2018-11-16Recruiting
Phase II Trial of Temozolomide, Carboplatin and Neupogen in High-Grade Gliomas, Both Newly-Diagnosed and Recurrent [NCT00006263]Phase 20 participants (Actual)Interventional1997-11-30Withdrawn
A Phase II Trial of Pre-Operative Taxol and Carboplatin in Women With Newly Diagnosed Locally Advanced Operable Breast Cancer [NCT00096343]Phase 231 participants (Actual)Interventional2002-10-31Completed
Phase III Trial Comparing 2 Chemotherapy Schedules (Preoperative vs Pre and Postoperative) in Stage I and II NSCLC [NCT00198354]Phase 3530 participants (Actual)Interventional2001-05-31Completed
NB2004 Trial Protocol for Risk Adapted Treatment of Children With Neuroblastoma [NCT00410631]Phase 3642 participants (Anticipated)Interventional2004-10-31Recruiting
A Phase 1 Evaluation Of Oral CI-1033 In Combination With Paclitaxel And Carboplatin As First-Line Chemotherapy In Patients With Advanced Non-Small Cell Lung Cancer [NCT00174356]Phase 139 participants Interventional2002-12-31Completed
Phase II Study of Carboplatin Plus Docetaxel (Taxotere) in Patients With Anaplastic Prostate Carcinoma [NCT00514540]Phase 2121 participants (Actual)Interventional2006-05-31Completed
Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index Low-Intermediate Risk, High-Intermediate Risk, or High Risk Diffuse Large B Cell Lymphoma [NCT00712582]Phase 296 participants (Actual)Interventional2008-07-01Completed
A Prospective, Single-arm, Single-center, Multi-cohort Phase II Clinical Study of HER2-positive and Triple-negative Breast Cancer Brain Metastases [NCT04303988]Phase 259 participants (Anticipated)Interventional2020-03-30Not yet recruiting
Phase II Trial of Preoperative Pemetrexed and Carboplatin in Patients With Select Stage IB, II, and III Non-Squamous Non-Small-Cell Lung Cancer [NCT00906282]Phase 246 participants (Actual)Interventional2009-06-30Completed
Combination of Non-Cytotoxic Suramin With Docetaxel and Carboplatin in Chemo-Naive Non-small Cell Lung Cancer (NSCLC): A Randomized Single-Blind Placebo-Controlled Phase II Study [NCT01038752]Phase 214 participants (Actual)Interventional2010-08-31Terminated
Response-based Treatment for Children With Unresectable Localized Soft Tissue Sarcomas [NCT02784015]Phase 241 participants (Anticipated)Interventional2016-05-31Recruiting
A Phase II Study in Newly Diagnosed Stage III/IV Epithelial Ovarian Cancer Evaluating Carbo/Taxol/Pembro in Patients Receiving Neoadjuvant Chemotherapy (NACT) Followed by Olaparib/Pembro Maintenance [NCT05952453]Phase 220 participants (Anticipated)Interventional2024-01-30Not yet recruiting
A Phase 1 Open Label, Multi-Arm, Multicenter Study of MK-4830 as Monotherapy and in Combination With Pembrolizumab for Participants With Advanced Solid Tumors [NCT03564691]Phase 1442 participants (Anticipated)Interventional2018-07-11Active, not recruiting
A Phase I Study of TAK-228 (MLN0128) in Combination With Carboplatin Plus Paclitaxel in Patients With Advanced Malignancies [NCT03430882]Phase 135 participants (Actual)Interventional2018-03-12Completed
A Phase 1 Study of RAD001 in Combination w/ Cetuximab and Cisplatin as First-line Therapy in Recurrent & Metastatic Squamous Cell Cancer of the Head & Neck [NCT01009346]Phase 1/Phase 29 participants (Actual)Interventional2009-10-31Terminated(stopped due to Toxicity)
Randomized Phase III Trial in MMR Deficient Endometrial Cancer Patients Comparing Chemotherapy Alone Versus Dostarlimab in First Line Advanced/Metastatic Setting [NCT05201547]Phase 3260 participants (Anticipated)Interventional2022-04-15Recruiting
A Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, PK, and Efficacy of MK-1084 as Monotherapy and in Combination With Pembrolizumab in Subjects With KRAS G12C Mutant Advanced Solid Tumors [NCT05067283]Phase 1450 participants (Anticipated)Interventional2021-12-17Recruiting
A Phase II/III Trial of Chemotherapy + Cetuximab vs Chemotherapy + Bevacizumab vs Atezolizumab + Bevacizumab Following Progression on Immune Checkpoint Inhibition in Recurrent/Metastatic Head and Neck Cancers [NCT05063552]Phase 2/Phase 3430 participants (Anticipated)Interventional2023-03-13Recruiting
A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma [NCT04854499]Phase 2230 participants (Anticipated)Interventional2021-09-07Recruiting
Limited Stage Small Cell Lung Cancer (LS-SCLC): A Phase III Randomized Study of Chemoradiation Versus Chemoradiation Plus Atezolizumab [NCT03811002]Phase 3545 participants (Anticipated)Interventional2019-07-26Recruiting
A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Pembrolizumab Plus Platinum-based Doublet Chemotherapy With or Without Canakinumab as First Line Therapy for Locally Advanced or Metastatic Non-squamous [NCT03631199]Phase 3673 participants (Actual)Interventional2018-12-21Active, not recruiting
Bevacizumab and Carboplatin/Paclitaxel and Radiation in Stage III Non-Small Cell Lung Cancer [NCT00578149]Phase 245 participants (Anticipated)Interventional2006-05-31Completed
Treatment Protocol for High-Risk PNET Brain Tumors in Children With Surgery, Sequential Chemotherapy, Conventional and High-Dose With Peripheral Blood Stem Cell Transplantation and Radiation Therapy [NCT00180791]Phase 271 participants (Anticipated)Interventional2002-07-31Recruiting
Phase III Trial Comparing Conventional RT With Concomitant CT Versus Accelerated RT With Concomitant CT Versus Very Accelerated RT Alone in Patients With Head and Neck Squamous Cell Carcinoma [NCT00158652]Phase 3840 participants (Actual)Interventional2000-03-31Completed
Phase II Trial of Carboplatin/Gemcitabine Plus Bevacizumab in Advanced Non-Small Cell Lung Cancer [NCT00150657]Phase 245 participants Interventional2004-11-30Recruiting
Phase I Study Of SU011248 In Combination With Paclitaxel/Carboplatin In Patients With Advanced Solid Malignancies [NCT00511849]Phase 143 participants (Actual)Interventional2005-11-30Completed
Phase III Study Comparing Osimertinib Monotherapy to Combination Therapy With Osimertinib,Carboplatin and Pemetrexed for Untreated Patients With Advanced Non-squamous Non-Small Cell Lung Cancer With Concurrent EGFR and TP53 Mutations [NCT04695925]Phase 3291 participants (Anticipated)Interventional2021-01-04Not yet recruiting
Large Cell Lymphoma, Pilot Study III [NCT00187070]8 participants (Actual)Interventional1997-12-31Completed
Phase I/II Trial of Infusional Gemcitabine in Combination With Carboplatin in Chemonaive Non-small Cell Carcinoma [NCT00212043]Phase 274 participants Interventional2000-07-31Completed
Anti-PD-1 Therapy in Combination With Platinum Chemotherapy for Platinum Resistant Ovarian, Fallopian Tube, and Primary Peritoneal Cancer [NCT03029598]Phase 1/Phase 229 participants (Actual)Interventional2017-03-14Completed
Reinduction Chemotherapy Containing Carboplatin and Paclitaxel With or Without Epoetin Alpha in Recurrent Platinum Sensitive Ovarian Cancer, Cancer of the Fallopian Tube or Peritoneum [NCT00189371]Phase 3300 participants Interventional2004-02-29Terminated
National, Randomized, Phase II Study Comparing Efficacy of Weekly Administration of Paclitaxel in Monotherapy or in Combination With Topotecan or Carboplatin in Patients With Epithelial Ovarian Cancer in Early Relapse [NCT00189566]Phase 2165 participants (Anticipated)Interventional2004-04-30Completed
Phase 1 Trial of MK-2870 as Monotherapy and in Combination With Pembrolizumab ± Chemotherapy in Subjects With Advanced Solid Tumors [NCT06049212]Phase 148 participants (Anticipated)Interventional2023-10-26Recruiting
A Phase III Randomized, Placebo-Controlled Study of Pembrolizumab (MK-3475, NSC #776864) in Addition to Paclitaxel and Carboplatin for Measurable Stage III or IVA, Stage IVB or Recurrent Endometrial Cancer [NCT03914612]Phase 3759 participants (Actual)Interventional2019-07-16Active, not recruiting
A Randomized Phase II Multi-centric Open Label Clinical Trial to Determine the Efficacy and Toxicity of Preoperative Chemotherapy With or Without Bevacizumab in Patients With Advanced Ovarian Cancer [NCT01847677]Phase 271 participants (Actual)Interventional2013-05-06Terminated
Neoadjuvant Nivolumab, or Nivolumab in Combination With Ipilimumab, in Resectable Non-Small-Cell Lung Cancer. [NCT02259621]Phase 245 participants (Anticipated)Interventional2014-09-30Active, not recruiting
National, Multicentric, Prospective Phase II Study Estimating the Interest of a Dose Decrease for Radiation Therapy Associated With a Carboplatine and Etoposide Based Chemotherapy for the Treatment of Standard Risk Adult Medulloblastomas [NCT01857453]Phase 297 participants (Anticipated)Interventional2013-04-10Recruiting
Neoadjuvant Chemotherapy of Nanoparticle Albumin-bound Paclitaxel/Carboplatin vs. Paclitaxel /Carboplatin in Stage Ⅱ B and IIIA Squamous Cell Carcinoma of the Lung: Parallel Control and Single Center [NCT01872403]Phase 2120 participants (Anticipated)Interventional2012-10-31Recruiting
A Randomized Phase I/II Study Of Sorafenib In Combination With High Does Chemoradiation In Patients With Stage IIIA/B Non-small Cell Lung Cancer (NSCLC) [NCT00547443]Phase 1/Phase 20 participants (Actual)Interventional2007-07-31Withdrawn(stopped due to Withdrawn as the sponsor has stopped the drug for NSCLC population)
A Phase 3, Multicenter, Randomized Open-Label Study to Compare the Efficacy and Safety of Tislelizumab (BGB A317, Anti-PD1 Antibody) Combined With Paclitaxel Plus Carboplatin or Nab Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Carboplatin Alone as F [NCT03594747]Phase 3360 participants (Actual)Interventional2018-07-30Completed
"A Phase II Study of Abraxane® and Carboplatin as First-line Treatment for Triple Negative (Demonstrating no Expression for Estrogen, Progesterone, or Human Epidermal Growth Factor Receptor 2 (HER2)Receptors) Metastatic Breast Cancer" [NCT01207102]Phase 210 participants (Actual)Interventional2011-08-31Terminated(stopped due to Low enrollment and there is insufficient data to publish.)
A Randomized, Phase 2 Trial of Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy (CHAMELEON) [NCT06020989]Phase 2129 participants (Anticipated)Interventional2023-09-30Not yet recruiting
Randomized Phase III Multicenter Trial of RRM1 & ERCC1 Directed Customized Chemotherapy Versus Standard of Care for 1st Line Treatment of Patients With Advanced Non-Small-Cell Lung Cancer [NCT00499109]Phase 3275 participants (Actual)Interventional2007-05-31Completed
A Multicentre Phase II Randomised Controlled Trial to Evaluate the Efficacy of Adaptive Therapy (AT) With Carboplatin, Based on Changes in CA125, in Patients With Relapsed Platinum-sensitive High Grade Serous or High Grade Endometrioid Ovarian Cancer [NCT05080556]Phase 280 participants (Anticipated)Interventional2023-04-30Recruiting
A Phase II Randomized Trial of Postoperative Chemotherapy or no Further Treatment for Patients With Node-negative Stage I-II Intermediate or High Risk Endometrial Cancer [NCT01244789]Phase 2244 participants (Actual)Interventional2011-12-31Active, not recruiting
Randomized, OpenLabel, Phase 3 Trial of Nivolumab Plus Ipilimumab or Nivolumab Plus Platinum Doublet Chemotherapy Versus Platinum Doublet Chemotherapy in Early Stage NSCLC [NCT02998528]Phase 3505 participants (Actual)Interventional2017-03-04Active, not recruiting
Matched Paired Pharmacodynamics and Feasibility Study of Durvalumab in Combination With Chemotherapy in Frontline Ovarian Cancer (N-Dur) [NCT02726997]Phase 1/Phase 218 participants (Actual)Interventional2016-07-06Active, not recruiting
A Phase Ib Dose-Escalation and Dose-Expansion Study Evaluating The Safety, Tolerability, Pharmacokinetics, And Efficacy Of Venetoclax In Combination With Atezolizumab, Carboplatin, And Etoposide In Patients With Untreated Extensive-Stage Small Cell Lung C [NCT04422210]Phase 12 participants (Actual)Interventional2020-09-22Terminated(stopped due to Decision to discontinue the study based on broader development and strategic prioritisation. The Sponsor concludes there is no benefit-risk impact on the GO41864 study.)
INTENSIVE CHEMOTHERAPY FOR RELAPSED OR REFRACTORY GERM CELL TUMORS EMPLOYING HIGH-DOSE CARBOPLATIN, ETOPOSIDE, AND THIOTEPA WITH AUTOLOGOUS BONE MARROW RESCUE FOR PATIENTS 15 TO 60 YEARS OF AGE [NCT00002508]Phase 1/Phase 20 participants Interventional1990-11-30Completed
PHASE III MULTICENTRE TRIAL OF TREATMENT OF NEUROBLASTOMA IN CHILDREN AND ADOLESCENTS [NCT00002802]Phase 3500 participants (Anticipated)Interventional1990-07-31Completed
MMT 95 Study For Rhabdomyosarcoma and Other Malignant Soft Tissue Tumors of Childhood [NCT00002898]Phase 3400 participants (Anticipated)Interventional1995-01-31Completed
A Phase II Trial of ICE Chemotherapy Followed by High Dose BEAM Chemotherapy With Autologous Peripheral Blood Progenitor Cell Transplantation in Patients >= 60 Years Old With Refractory or Relapsed Intermediate Grade Non-Hodgkin's Lymphoma [NCT00002982]Phase 20 participants Interventional1997-01-31Completed
Amifostine (Ethyol) as a Protectant in Metastatic Ovarian and Non-Small Cell Lung Cancer in Paclitaxel/Carboplatin-Treated Patients: A Comparative Trial [NCT00003072]Phase 280 participants (Anticipated)Interventional1997-05-31Completed
Phase I Trial of Dose-Dense Gemcitabine, Doxorubicin, Then Paclitaxel Plus Carboplatin In Patients With Transitional Cell Carcinoma of the Urothelium and Impaired Renal Function [NCT00003342]Phase 130 participants (Anticipated)Interventional1997-12-31Completed
A Phase I Feasibility Trial of Carboplatin, Paclitaxel, and Gemcitabine in Patients With Previously Untreated Epithelial Ovarian Carcinoma and Primary Peritoneal Carcinoma [NCT00003378]Phase 145 participants (Anticipated)Interventional1998-08-31Terminated
A Randomized Phase III Trial of Paclitaxel, Carboplatin and Etoposide Vs. 5-Fluorouracil and Folinic Acid in the Treatment of Patients With Adenocarcinoma of Unknown Primary Site [NCT00003558]Phase 3140 participants (Anticipated)Interventional1998-08-31Active, not recruiting
Randomized Phase II Trial of Paclitaxel, Carboplatin and rhuMAb Her-2 (Herceptin) as First-Line Chemotherapy in Patients With Metastatic Breast Cancer Who Overexpress Her-2 [NCT00003612]Phase 292 participants (Actual)Interventional1999-04-30Completed
Liver Tumour Studies - Hepatoblastoma and Hepatocellular Carcinoma [NCT00003912]Phase 3260 participants (Anticipated)Interventional1998-06-30Completed
A Phase I Trial of Herceptin and Interleukin-12 [NCT00004074]Phase 115 participants (Actual)Interventional1999-08-31Completed
Randomized Phase II Trail of Carboplatin and Gemcitabine Untreated Stage IIIB-pleural Effusion and Stage IV Lung Cancer [NCT00247416]Phase 260 participants (Actual)Interventional2005-08-31Completed
Phase I Trial of BKM120 in Combination With Carboplatin and Pemetrexed in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) [NCT01723800]Phase 19 participants (Actual)Interventional2013-07-31Completed
Randomized Phase III Multicenter Trial of Customized Chemotherapy Versus Standard of Care for1st Line Treatment of Elderly Patients With Advanced Non-Small-Cell Lung Cancer [NCT03402048]Phase 3567 participants (Anticipated)Interventional2012-07-31Recruiting
A Phase 1 Study of CC-486 as a Single Agent and in Combination With Carboplatin or ABI-007 in Subjects With Relapsed or Refractory Solid Tumors [NCT01478685]Phase 1169 participants (Actual)Interventional2011-11-29Completed
Phase I/IIB Study of Induction Chemotherapy With XELOX, Followed by Radiation Therapy and Dose Escalation of RAD001 in Patients With Esophageal Cancer [NCT01490749]Phase 117 participants (Actual)Interventional2012-02-29Completed
A Phase II, Double-Blind, Placebo-Controlled, Randomized Study Evaluating the Safety and Efficacy of Carboplatin/Paclitaxel and Carboplatin/Paclitaxel/Bevacizumab With and Without GDC-0941 in Patients With Previously Untreated Advanced or Recurrent Non-sm [NCT01493843]Phase 2501 participants (Actual)Interventional2012-01-20Completed
A Phase II Study of Concurrent Nab-Paclitaxel, Carboplatin and Thoracic Radiotherapy in Local Advanced Squamous Cell Lung Cancer [NCT01494415]Phase 221 participants (Anticipated)Interventional2012-07-31Recruiting
A Phase II Trial of Radiation Therapy With Concurrent Paclitaxel/Carboplatin Chemotherapy in High-risk Cervical Cancer Patients After Radical Hysterectomy [NCT00340184]Phase 255 participants Interventional2004-08-31Completed
Randomised Study With Docetaxel, Cisplatin and Cyclophosphamide vs Docetaxel and Carboplatin as First Line Chemotherapy With Advanced or Metastatic Ovarian Cancer [NCT00452985]30 participants (Actual)Observational2002-02-28Completed
Randomized Phase II/III Study of Intensified Alkylating Agent Chemotherapy With Peripheral Blood Progenitor Cell Support in the Preoperative Chemotherapy of Breast Tumors That Are Deficient for Homologous Recombination. [NCT00448266]Phase 2/Phase 312 participants (Actual)Interventional2007-05-31Terminated(stopped due to Activation of a similar multicenter study for same population)
Gemcitabine Plus Carboplatin in Patients With Pretreated Metastatic Breast Cancer [NCT00450762]Phase 20 participants Interventional2004-03-31Completed
A Phase I/II Study of ATN-161 and Carboplatin in Adult Patients With Recurrent Intracranial Malignant Glioma [NCT00352313]Phase 1/Phase 282 participants (Anticipated)Interventional2006-05-31Completed
A Multicenter Phase II Study of Carboplatin Plus Gemcitabine Followed by Concomitant Chemoradiation in Patients With Non-resectable Stage III Non-Small-Cell-Lung Cancer [NCT00463515]Phase 277 participants Interventional2003-01-31Completed
A Phase II Pilot Trial of Radiation Therapy With Concurrent and Adjuvant Temozolomide, Tamoxifen and Carboplatin (T2C) in the Treatment of Patients With Primary Central Nervous System Malignant Gliomas [NCT00492687]Phase 280 participants (Anticipated)Interventional2006-12-31Recruiting
Phase II Trial of Enzastaurin Plus Carboplatin and Gemcitabine (ECoG) in Bevacizumab-Ineligible Patients and Enzastaurin Plus Carboplatin, Gemcitabine and Bevacizumab (B-ECoG) in Bevacizumab-Eligible Patients With Advanced Non-Small Cell Lung Cancer (NSCL [NCT00469976]Phase 20 participants (Actual)Interventional2007-06-30Withdrawn(stopped due to ECOG will not proceed with activation)
A Phase II Study of Carboplatin in Combination With Gemcitabine as a Dose Dense Schedule in Patients With Locally Advanced or Metastatic Breast Cancer That Are Resistant to Anthracyclines & Taxanes [NCT00470249]Phase 25 participants (Actual)Interventional2006-07-15Terminated(stopped due to Due to difficulty in recruitment)
A RANDOMIZED, DOUBLE-BLIND BRIDGING SAFETY AND EFFICACY STUDY OF PF-06439535 (CN) PLUS PACLITAXEL-CARBOPLATIN VERSUS BEVACIZUMAB PLUS PACLITAXEL-CARBOPLATIN FOR THE FIRST-LINE TREATMENT OF CHINESE PARTICIPANTS WITH ADVANCED NON-SQUAMOUS NON-SMALL CELL LUN [NCT04325698]Phase 38 participants (Actual)Interventional2020-06-11Terminated(stopped due to The study was terminated as part of the decision by Pfizer to halt its biosimilars programs in China.)
Folfirinox Versus Platinum - Etoposide as First Line Chemotherapy for Metastatic Grade 3 Poorly Differentiated Neuroendocrine Carcinoma of Gastro Entero Pancreatic and Unknown Primary Associated With Molecular Profiling for Therapeutic Targets & Predictiv [NCT04325425]Phase 2218 participants (Anticipated)Interventional2020-09-01Recruiting
Randomized Phase II Study Assessing the Combination of Vinflunine With Gemcitabine and Vinflunine With Carboplatin in Patients Ineligible to Cisplatin With Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium [NCT01599013]Phase 269 participants (Actual)Interventional2011-02-28Completed
A Phase I Trial of Epirubicin, Carboplatin and Capecitabine in Adult Cancer Patients [NCT00486356]Phase 146 participants (Actual)Interventional2004-10-31Completed
A Phase I, Open-label Study to Assess the Safety and Tolerability of AZD0530 in Combination With Carboplatin and/or Paclitaxel Chemotherapy in Patients With Solid Tumours [NCT00496028]Phase 1148 participants (Actual)Interventional2007-03-31Completed
A Phase I Study of a Novel Chemotherapeutic Regimen: Topotecan, Ifosfamide and Carboplatin (TIC) in Children and Young Adults With Solid Tumors-- A Limited Multi-Institution Study [NCT00502892]Phase 12 participants (Actual)Interventional2004-08-31Completed
Phase I/II Study on Induction Chemotherapy Followed by Chemoradiation With or Without Lapatinib, a Dual EGFR/ErbB2 Kinase Inhibitor, in Patients With Locally Advanced Larynx and Hypopharynx Squamous Cell Carcinoma [NCT00498953]Phase 1/Phase 27 participants (Actual)Interventional2007-05-31Completed
Phase II Study of Pembrolizumab in Combination With Cisplatin or Carboplatin and Pemetrexed as Induction Chemo+Immunotherapy in Resectable Epithelioid and Biphasic Pleural Mesothelioma (CHIMERA Study) [NCT06155279]Phase 240 participants (Anticipated)Interventional2024-06-30Not yet recruiting
Phase II Trial of LP-300 in Combination With Carboplatin and Pemetrexed in Never Smoker Patients With Relapsed Advanced Primary Adenocarcinoma of the Lung After Treatment With Tyrosine Kinase Inhibitors (The HARMONIC Study) [NCT05456256]Phase 290 participants (Anticipated)Interventional2022-08-12Recruiting
A Phase 3, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) Versus Investigator's Choice of Chemotherapy in Patients Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy in First-line Locally Recurrent Inoperable or Metastatic Triple-n [NCT05374512]Phase 3600 participants (Anticipated)Interventional2022-05-16Recruiting
A Phase IB, Open-Label, Multicenter, Single Arm Study Evaluating the Preliminary Efficacy, Safety, and Pharmacokinetics of Glofitamab in Combination With Rituximab Plus Ifosfamide, Carboplatin Etoposide Phosphate in Patients With Relapsed/Refractory Trans [NCT05364424]Phase 140 participants (Anticipated)Interventional2022-11-04Recruiting
A Phase 1 First-in-human Study of BMS-986406 as Monotherapy and Combination Therapies in Participants With Advanced Malignant Tumors [NCT05298592]Phase 1154 participants (Anticipated)Interventional2022-03-31Recruiting
A Phase 3, Randomized Study of Nivolumab Plus Ipilimumab in Combination With Chemotherapy vs Chemotherapy Alone as First Line Therapy in Stage IV Non-Small Cell Lung Cancer [NCT03215706]Phase 3719 participants (Actual)Interventional2017-08-24Active, not recruiting
A Phase II Study of Carboplatin/Paclitaxel/Bevacizumab in the Treatment of Advanced Stage Endometrial Carcinoma [NCT00513786]Phase 238 participants (Actual)Interventional2007-08-01Completed
Chemotherapy Plus Gefitinib Versus Gefitinib Alone as First-line Treatment for Patients With Advanced Lung Adenocarcinoma and Sensitive EGFR Mutations: a Randomized Controlled Trial [NCT02951637]Phase 2300 participants (Anticipated)Interventional2016-12-31Not yet recruiting
A Phase 1 Study of Paclitaxel and Carboplatin in Solid Tumors (With Focus on Upper Aerodigestive Cancers) in Persons With HIV Infection [NCT01249443]Phase 117 participants (Actual)Interventional2013-11-30Terminated(stopped due to Inadequate accrual rate)
Phase I Study Panitumumab Plus Chemoradiotherapy and Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck [NCT00513383]Phase 134 participants (Actual)Interventional2006-04-30Completed
Optimization for the Treatment of Advanced Pulmonary Large Cell Neuroendocrine Carcinoma: a Prospective, Randomized, Open-label, Phase 2 Study [NCT02943798]Phase 2118 participants (Anticipated)Interventional2016-12-31Not yet recruiting
A Pilot Study of Standard-Dose Rituximab, Ifosfamide, Carboplatin and Etoposide (RICE) Plus Bortezomib (Velcade) in a Dose-Escalating Fashion for Patients With Relapsed or Primary Refractory Aggressive B-Cell Non-Hodgkin's Lymphoma Who Are Candidates for [NCT00515138]Early Phase 17 participants (Actual)Interventional2007-05-31Terminated(stopped due to Investigator left institution. 7 patients accrued and there is insufficient data to analyze.)
[NCT02940990]Phase 250 participants (Anticipated)Interventional2016-11-30Not yet recruiting
Multicenter, Open-label Study of Safety and Efficacy of Quisinostat in Combination With Paclitaxel + Carboplatin Chemotherapy in Patients With Metastatic or Locally Advanced Epithelial Ovarian Cancer, Primarily Peritoneal or Fallopian Tube Carcinoma, Resi [NCT02948075]Phase 231 participants (Actual)Interventional2015-09-30Completed
Phase I Trial of Sequential Azacitidine and Valproic Acid Plus Carboplatin in the Treatment of Patients With Platinum Resistant Epithelial Ovarian Cancer [NCT00529022]Phase 136 participants (Actual)Interventional2007-08-31Completed
A Randomized, Phase 3, Open-label Study to Investigate the Pharmacokinetics and Safety of Subcutaneous Pembrolizumab Versus Intravenous Pembrolizumab, Administered With Platinum Doublet Chemotherapy, in the First-Line Treatment of Participants With Metast [NCT04956692]Phase 3531 participants (Actual)Interventional2021-08-05Active, not recruiting
A Phase 3, Randomized, Double-blind Study of Neoadjuvant Chemotherapy Plus Nivolumab Versus Neoadjuvant Chemotherapy Plus Placebo, Followed by Surgical Resection and Adjuvant Treatment With Nivolumab or Placebo for Participants With Resectable Stage II-II [NCT04025879]Phase 3452 participants (Anticipated)Interventional2019-11-05Active, not recruiting
Randomized Phase II Study on Decitabine Plus Carboplatin Versus Physician's Choice Chemotherapy in Recurrent, Platinum-resistant Ovarian Cancer. [NCT03467178]Phase 2119 participants (Anticipated)Interventional2018-07-30Recruiting
Three Cycles Versus Six Cycles of Adjuvant Chemotherapy for the Patients With High-risk Retinoblastoma After Enucleation: Prospective Randomized Control Study [NCT01906814]Phase 3179 participants (Actual)Interventional2013-08-31Active, not recruiting
Phase Ib / II Trial Evaluating the Association Myocet ® - Carboplatine in Patients Having a Cancer of the Ovary in Relapse, Sensitive to the Platinum [NCT01705158]Phase 1/Phase 287 participants (Actual)Interventional2012-10-31Completed
Phase I-II Study of Concurrent Adjuvant Systemic Therapy and Accelerated Radiotherapy (Over 3 Weeks) [NCT01289353]Phase 1/Phase 292 participants (Actual)Interventional2009-03-06Completed
Phase II Trial of Induction Chemotherapy Followed by Chemoradiotherapy With Paclitaxel and Carboplatin Before Minimal Invasive Surgery in Patients With Localized Esophageal and Gastro-esophageal Junction Cancer [NCT02924909]Phase 250 participants (Anticipated)Interventional2017-02-01Recruiting
Phase 1 Dose Escalation Study of LY2090314 in Patients With Advanced or Metastatic Cancer in Combination With Pemetrexed and Carboplatin [NCT01287520]Phase 141 participants (Actual)Interventional2007-11-30Completed
Randomized, Multicenter, Double-Blind, Phase 3 Trial Comparing the Efficacy of Ipilimumab in Addition to Paclitaxel and Carboplatin Versus Placebo in Addition to Paclitaxel and Carboplatin in Subjects With Stage IV/Recurrent Non Small Cell Lung Cancer (NS [NCT01285609]Phase 31,289 participants (Actual)Interventional2011-01-16Completed
Triple Negative Trial: A Randomised Phase III Trial of Carboplatin Compared to Docetaxel for Patients With Metastatic or Recurrent Locally Advanced ER-, PR- and HER2- Breast Cancer. [NCT00532727]Phase 3400 participants (Anticipated)Interventional2008-01-31Active, not recruiting
A Phase 1b/2 Randomized Study of MEDI-575 in Combination With Carboplatin Plus Paclitaxel Versus Carboplatin Plus Paclitaxel Alone in Adult Subjects With Previously Untreated, Advanced Non-Small Cell Lung Cancer [NCT01268059]Phase 1/Phase 299 participants (Actual)Interventional2010-12-16Terminated(stopped due to In conjunction with the overall risk-benefit assessment, study was terminated prematurely due to safety concerns.)
A Prospective Randomised Phase III Trial to Evaluate Optimal Treatment Duration of First-line Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Primary Epithelial Ovarian, Fallopian Tube or Peritoneal Cancer [NCT01462890]Phase 3927 participants (Actual)Interventional2011-11-30Completed
Acalabrutinib Plus RICE for Patients With Relapsed/Refractory DLBCL Followed by Autologous Hematopoietic Cell Transplantation and Acalabrutinib Maintenance Therapy [NCT03736616]Phase 247 participants (Anticipated)Interventional2019-08-16Recruiting
A Two-Part Study in Japanese Patients With Advanced or Metastatic NSCLC. Open-Label Phase I to Assess the Safety & Tolerability of AZD2171 in Combination With Pac/Carb, Then a Phase II, Randomised, Double-Blind Study to Assess the Efficacy of Pac/Carb Alo [NCT00539331]Phase 16 participants (Actual)Interventional2007-09-30Terminated
A Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Advanced Solid Malignancies [NCT00535119]Phase 1107 participants (Actual)Interventional2007-09-30Completed
Prospective, Randomized Phase II Clinical Trial to Select Primary Chemotherapy With Carboplatin and Docetaxel in Patients With Advanced Ovarian Cancer Stage FIGO IIIC and IV [NCT00551577]Phase 2100 participants (Anticipated)Interventional2003-03-31Recruiting
A Single -Arm, Open-label, Multicenter Phase II Study of Camrelizumab Combined With Apatinib ,Carboplatin and Etoposide in Participants With Untreated Extensive-Stage (ES) Small Cell Lung Cancer (SCLC) [NCT04683198]Phase 269 participants (Anticipated)Interventional2021-04-01Not yet recruiting
Pilot Study Targeting Residual Hypermethylation in Early Stage Non-Small Cell Lung Cancer As Part of Adjuvant Therapy and Preventive Strategy [NCT01209520]6 participants (Actual)Interventional2009-07-31Completed
Efficacy and Safety of Paclitaxel (Albumin-bound) Combination With Carboplatin in the Treatment of Platinum-sensitive Recurrent Ovarian Cancer: a Multicenter, Open, Phase 2 Clinical Study [NCT04661696]Phase 275 participants (Anticipated)Interventional2020-12-09Not yet recruiting
KANDOVA - A Two-Part Phase Ib/IIa Study to Evaluate the Safety and Tolerability of KAND567, in Combination With Carboplatin Therapy, and to Determine the Recommended Phase II Dose (RPIID) of KAND567: An Open-Label, Multicenter Dose Escalation Study With a [NCT06087289]Phase 1/Phase 230 participants (Anticipated)Interventional2023-04-20Recruiting
Phase II, Open Label, Single Arm Study of PembrolizumAb combiNeD With Cisplatin or carbOplatin and Etoposide in Treatment naïve Advanced meRkel Cell cArcinoma (MCC) (PANDORA Trial) [NCT06086288]Phase 235 participants (Anticipated)Interventional2023-11-30Not yet recruiting
A Randomized Controlled Study of a Fasting Mimicking Diet (FMD) in Conjunction With Combination Carboplatin and Paclitaxel in the Treatment of Patients With Advanced or Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancer [NCT05921149]170 participants (Anticipated)Interventional2023-12-01Not yet recruiting
Phase 1b/2, Single Arm Clinical Trial to Evaluate the Safety and Activity of Oregovomab and Bevacizumab, Paclitaxel Carboplatin as a Combinatorial Strategy in Subjects With BRCA-wild Type Platinum Sensitive Recurrent Ovarian Cancer [NCT04938583]Phase 1/Phase 254 participants (Anticipated)Interventional2021-03-17Recruiting
Phase II Study of First Line Weekly Chemo/Immunotherapy for Metastatic Head/Neck Squamous Cell Carcinoma Patients [NCT04858269]Phase 235 participants (Anticipated)Interventional2021-05-27Recruiting
A Phase II Randomized, Multi-Center, Double-Blind, Global Study to Determine the Efficacy and Safety of Durvalumab Plus Olaparib Combination Therapy Compared With Durvalumab Monotherapy as Maintenance Therapy in Patients Whose Disease Has Not Progressed F [NCT03775486]Phase 2401 participants (Actual)Interventional2018-12-21Active, not recruiting
A Randomized Phase II Study of Pembrolizumab, an Anti-Programmed Cell Death (PD)-1 Antibody, in Combination With Carboplatin Compared to Carboplatin Alone in Breast Cancer Patients With Chest Wall Disease [NCT03095352]Phase 284 participants (Anticipated)Interventional2017-09-02Recruiting
A Phase II Study of Olaparib Plus Cediranib in Combination With Standard Therapy for Small Cell Lung Cancer [NCT02899728]Phase 29 participants (Actual)Interventional2018-03-30Terminated(stopped due to Inadequate accrual rate)
Phase I/II Study of Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide for Refractory or Relapsed Aggressive B-cell Lymphomas [NCT01458366]Phase 1/Phase 238 participants (Actual)Interventional2011-11-09Completed
Phase 1b/2a Safety and Tolerability Study of Bemcentinib With Pembrolizumab/Carboplatin/Pemetrexed in Subjects With Untreated Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Without/With a STK11 Mutation [NCT05469178]Phase 1/Phase 264 participants (Anticipated)Interventional2022-12-14Recruiting
A Phase 1/2 Study to Assess the Safety and Efficacy of Lorvotuzumab Mertansine in Combination With Carboplatin/Etoposide in Patients With Advanced Solid Tumors Including Extensive Stage Small Cell Lung Cancer [NCT01237678]Phase 1/Phase 2181 participants (Actual)Interventional2010-11-30Terminated(stopped due to Study was stopped early due to lack of efficacy signal and safety concerns)
An Open-label, Multicenter, Phase Ib/II Study of AK104, Combined Chemotherapy as First-line Therapy to Treat Locally Advanced or Metastatic Non-small Cell Lung Carcinoma [NCT04647344]Phase 1/Phase 260 participants (Anticipated)Interventional2020-11-24Active, not recruiting
A Phase II Single-arm Clinical Trial of Inetetamab Combined With Pyrotinib and Chemotherapy in the Treatment of HER2 Positive Metastatic Breast Cancer [NCT04681911]Phase 271 participants (Anticipated)Interventional2020-09-09Recruiting
Randomized Phase III Trial on Trabectedin (ET-743) vs Clinician's Choice Chemotherapy in Recurrent Ovarian, Primary Peritoneal or Fallopian Tube Cancers of BRCA Mutated or BRCAness Phenotype Patients [NCT02903004]Phase 3242 participants (Actual)Interventional2016-04-11Completed
Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer [NCT01220128]Phase 266 participants (Actual)Interventional2011-04-11Terminated(stopped due to Study termination due to negative Ph III of another study product from same technology platform.)
Phase II Trial of Pulsed Paclitaxel With Concurrent Radiotherapy,and Adjuvant Chemotherapy in Stage III Non-Small Cell Lung Cancer [NCT00449657]Phase 224 participants (Actual)Interventional2007-02-28Terminated(stopped due to Poor accrual, change in standard of care.)
Combination of Gefitinib With Chemotherapy or Anti-angiogenesis as 1st Line Treatment in Advanced NSCLC Patients Detected With Bim Deletion or Low EGFR Activating Mutation Abundance [NCT02930954]Phase 2180 participants (Anticipated)Interventional2016-11-30Not yet recruiting
Randomized, Double-Blind, Multicenter, Phase 3 Study Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Previously Untreated Advanced or Metastatic Squamous Non-Small Cell Lung Cancer (NSCLC) [NCT02106546]Phase 3970 participants (Actual)Interventional2014-04-10Completed
A Phase 1b/2 Trial of AMG 386 in Combination With Pemetrexed and Carboplatin as First Line Treatment of Metastatic Non-Squamous Non-Small Cell Lung Cancer [NCT01666977]Phase 1/Phase 236 participants (Actual)Interventional2012-08-31Completed
A Single-arm, Multi-institutional, Phase 2 Study of a Pembrolizumab-based Organ Preservation Strategy for Locally Advanced Larynx Cancers [NCT04943445]Phase 243 participants (Actual)Interventional2022-02-22Active, not recruiting
A Phase II Trial of Pembrolizumab Combined With Cisplatin-based Chemotherapy as First-line Systemic Therapy in Advanced Penile Cancer [NCT04224740]Phase 237 participants (Actual)Interventional2020-06-15Active, not recruiting
Personalized Escalation of Consolidation Treatment Following Chemoradiotherapy and Immunotherapy in Stage III NSCLC [NCT04585490]Phase 348 participants (Anticipated)Interventional2021-08-25Recruiting
ENGOT-OV42 / NSGO-AVATAR: A Three-arm Randomized Study to Evaluate the Efficacy of Niraparib-bevacizumab-dostarlimab Triplet Combination Against Niraparib-bevacizumab Doublet Combination and Against Standard of Care Therapy in Women With Relapsed Ovarian [NCT03806049]Phase 30 participants (Actual)Interventional2019-12-31Withdrawn(stopped due to Lack of financial support)
A Phase II Two Cohorts Prospective Study to Evaluate the Efficacy and Safety of Tislelizumab Combined With Chemotherapy With or Without Bevacizumab in Non-squamous NSCLC With EGFR Sensitizing Mutation Who Failed EGFR TKI Therapy [NCT04405674]Phase 2120 participants (Anticipated)Interventional2020-07-15Recruiting
A Phase 2 Study of Sequential and Concurrent Chemoradiation for Patients With Advanced Nasopharyngeal Carcinoma (NPC) [NCT00896181]Phase 226 participants (Actual)Interventional2008-12-10Completed
A Phase I Investigator Sponsored Trial of Selinexor (KPT-330), a Selective Inhibitor of Nuclear Export / SINE™ Compound and Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed or Refractory Peripheral T-cell Lymphoma [NCT03212937]Phase 111 participants (Actual)Interventional2016-07-01Completed
A Clinical Study to Explore the Efficacy and Safety of Tislelizumab in Combination With Bevacizumab and Chemotherapy in Patients With Persistent, Recurrent, or Metastatic Cervical Cancer [NCT05247619]Phase 249 participants (Anticipated)Interventional2022-06-30Recruiting
The Exploration of Immunodynamic Monitoring in the Population Evaluation of Neoadjuvant Chemotherapy Immunotherapy in Patients With Solid Tumor of the Chest. [NCT05044728]Phase 280 participants (Anticipated)Interventional2021-04-01Recruiting
Open-Label, Multicenter, Phase Ⅱ Study Of Paclitaxel (Albumin Bound),Bleomycin And Cisplatin Or Carboplatin As First-Line Treatment In Patients With Recurrent Or Metastatic Squamous Cell Carcinoma Of The Head And Neck [NCT03830385]Phase 251 participants (Anticipated)Interventional2019-02-15Recruiting
Phase II Study Of Carboplatin Plus Paclitaxel Treatment Of Advanced Thymoma Or Thymic Carcinoma [NCT00010257]Phase 246 participants (Actual)Interventional2001-06-19Completed
One-arm, Multi-center Clinical Trial of Paclitaxel (Albumin-binding) Combined With Carboplatin for Castration-resistant Prostate Cancer [NCT04148885]Phase 1/Phase 244 participants (Anticipated)Interventional2019-11-30Not yet recruiting
Intestinal Microbiota Impact for Prognosis and Treatment Outcomes in Early Luminal Breast Cancer and Pancreatic Cancer Patients [NCT05580887]35 participants (Anticipated)Observational2022-05-12Recruiting
Phase II Study of Bevacizumab Plus Irinotecan and Carboplatin for Recurrent Malignant Glioma Patients [NCT00953121]Phase 2104 participants (Actual)Interventional2009-09-30Completed
A Phase II Study of Everolimus in Combination With Paclitaxel and Carboplatin in Patients With Metastatic Melanoma [NCT01014351]Phase 270 participants (Actual)Interventional2010-02-28Completed
A Phase I/II Study of Temsirolimus + Weekly Paclitaxel + Carboplatin for Recurrent or Metastatic Head and Neck Squamous Cell Cancer (HNSCC) [NCT01016769]Phase 1/Phase 248 participants (Actual)Interventional2009-11-30Completed
A Phase Ib, Open-label, Dose Escalation Trial Investigating Different Doses and Schedules of Sym004 in Combination With Platinum-doublets in Subjects With Stage IV Non-small Cell Lung Cancer [NCT02083679]Phase 115 participants (Actual)Interventional2014-07-31Terminated(stopped due to Sponsor the return rights of the compound to the collaboration partner for further clinical development)
LCI-BRE-MTN-NIR-001: A Phase I Study of Niraparib in Combination With Standard Chemotherapy in Metastatic Triple-Negative Breast Cancer [NCT04762901]Phase 10 participants (Actual)Interventional2021-04-01Withdrawn(stopped due to Funding was terminated.)
A Randomized, Double-Blind, Phase 2 Safety Study of Cetuximab, Using ImClone Versus Boehringer Ingelheim Manufacturing Processes, in Combination With Cisplatin or Carboplatin and 5-Fluorouracil in the First-Line Treatment of Patients With Locoregionally R [NCT01081041]Phase 2187 participants (Actual)Interventional2010-06-30Completed
A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]-Pevonedistat in Patients With Advanced Solid Tumors [NCT03057366]Phase 18 participants (Actual)Interventional2017-05-11Completed
A Phase II Trial of Carboplatin +/- Tocilizumab as Initial Therapy for Metastatic Triple Negative and ER-low Breast Cancers [NCT05846789]Phase 2168 participants (Anticipated)Interventional2024-01-31Recruiting
A PILOT TRIAL OF INTERLEUKIN-2 WITH G-CSF AS PRIMING THERAPY FOR PERIPHERAL BLOOD STEM CELL HARVESTING IN PATIENTS WITH ADVANCED BREAST CANCER: STAMP V HIGH DOSE CHEMOTHERAPY, STEM CELL INFUSION AND POST-INFUSION G-CSF AND INTERLEUKIN-2 [NCT00002616]Phase 136 participants (Anticipated)Interventional1995-02-28Active, not recruiting
A Comparison of Intensive Sequential Chemotherapy Using Doxorubicin Plus Paclitaxel Plus Cyclophosphamide With High Dose Chemotherapy and Autologous Hematopoietic Progenitor Cell Support for Primary Breast Cancer in Women With 4-9 Involved Axillary Lymph [NCT00002772]Phase 3602 participants (Actual)Interventional1996-07-31Terminated(stopped due to poor accrual)
PHASE I/II TRIAL OF THE ADDITION OF TAXOL TO THE HIGH DOSE CARBOPLATIN AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS PERIPHERAL BLOOD PROGENITOR CELL SUPPORT IN PATIENTS WITH BREAST CANCER [NCT00002628]Phase 1/Phase 250 participants (Anticipated)Interventional1994-11-30Active, not recruiting
A Phase II Study to Evaluate the Efficacy, Safety, and Tolerability of KN046 in Patients With Advanced Non-small Cell Lung Cancer [NCT03838848]Phase 2120 participants (Actual)Interventional2019-05-05Terminated(stopped due to Cohort A,B,C end enrollments. Cohort D and E were considered to have no significant clinical benefit at the SMC meeting and decided to terminate enrollment.)
Initial Clinical Evaluation of the Combination of Paclitaxel and Carboplatin With Modulation of Toxicity With GCSF and Amifostine [NCT00003294]Phase 124 participants (Anticipated)Interventional1997-05-31Completed
Phase III Study of Cyclophosphamide, Doxorubicin and Etoposide Compared to Carboplatin and Taxol in Patients With Extensive Disease Small Cell Lung Cancer [NCT00003696]Phase 3250 participants (Anticipated)Interventional1998-10-31Active, not recruiting
A Phase I/II Study to Determine the Maximum Tolerated Doses of Oral Topotecan, Carboplatin and Paclitaxel Administered Every 21 Days to Patients With Epithelial Ovarian Cancer Stages IIb, IIc, III and IV [NCT00003732]Phase 280 participants (Anticipated)Interventional1998-09-30Completed
Treatment of High Risk Central Nervous System Embryonal Tumors With Conventional Radiotherapy and Intensive Consolidation Chemotherapy With Peripheral Blood Progenitor Cell (PBSC) Support [NCT00003846]Phase 225 participants (Actual)Interventional1999-07-31Completed
Phase II Study of Intensive Chemotherapy With Autologous Peripheral Blood Stem Cell Support in Patients With Cisplatin Resistant Germ Cell Tumors [NCT00003852]Phase 245 participants (Anticipated)Interventional1998-03-31Terminated(stopped due to lack of patient inclusion)
A Phase III Study of High-Dose Chemotherapy Using Busulfan, Melphalan and Thiotepa Versus Cyclophosphamide,Thiotepa, Carboplatin Followed by Autologous Stem Cell Transplantation in Patients With High-Risk Primary Stage II or III (Non-Inflammatory) Breast [NCT00003972]Phase 3280 participants (Anticipated)Interventional1998-07-31Completed
A Randomized Study of Purged Versus Unpurged Peripheral Blood Stem Cell Transplant Following Dose Intensive Induction Therapy for High Risk Neuroblastoma [NCT00004188]Phase 3495 participants (Actual)Interventional2001-02-28Completed
A Data Collection Study to Compare the Outcome for Children With Advanced Unilateral Retinoblastoma Treated With or Without Post-Enucleation Chemotherapy ± Radiotherapy on RB 2005 11 With Historical Controls Receiving no Additional Therapy [NCT00360750]0 participants Interventional2005-09-30Active, not recruiting
A Phase 1B, Open-Label, Dose Escalation Study Evaluating the Safety of BSI-201 in Combination With Chemotherapeutic Regimens in Subjects With Advanced Solid Tumors [NCT00422682]Phase 1136 participants (Actual)Interventional2007-01-31Completed
[NCT01276548]Phase 2102 participants (Actual)Interventional2009-10-31Completed
[NCT01838538]Phase 254 participants (Anticipated)Interventional2011-06-30Recruiting
A Randomized Controlled Trial Comparing Safety and Efficacy of Carboplatin and Paclitaxel Plus or Minus Sorafenib (BAY43-9006) in Chemonaive Patients With Stage IIIB-IV Non-Small Cell Lung Cancer (NSCLC) [NCT00558636]Phase 391 participants (Actual)Interventional2007-09-30Terminated(stopped due to Terminated early when the results from Study NCT00300885 showed an overall lack of efficacy in NSCLC and increased mortality in subjects with squamous subtype.)
A Phase II Prospective Single-arm Clinical Study of Aribulin Combined With Carboplatin and Bevacizumab in the First-line Treatment of Platinum-sensitive Recurrent Ovarian Cancer [NCT05965141]Phase 1/Phase 238 participants (Anticipated)Interventional2023-08-01Not yet recruiting
Phase 2 Study of Alisertib as a Single Agent in Recurrent or Progressive Central Nervous System (CNS) Atypical Teratoid Rhabdoid Tumors (AT/RT) and Extra-CNS Malignant Rhabdoid Tumors (MRT) and in Combination Therapy in Newly Diagnosed AT/RT [NCT02114229]Phase 2125 participants (Actual)Interventional2014-05-14Active, not recruiting
A Phase I, Open-Label Study to Assess the Safety and Tolerability of KU-0059436 in Combination With Carboplatin, KU-0059436 in Combination With a Paclitaxel/Carboplatin T/C Doublet and KU-0059436 in Combination With Paclitaxel in the Treatment of Patients [NCT00516724]Phase 1189 participants (Actual)Interventional2007-06-22Active, not recruiting
Randomized Phase III Trial Comparing Concurrent Chemoradiation and Adjuvant Chemotherapy With Pelvic Radiation Alone in High Risk and Advanced Stage Endometrial Carcinoma: PORTEC-3 [NCT00411138]Phase 3670 participants (Anticipated)Interventional2006-11-23Active, not recruiting
A Phase I/II Study Afatinib/Carboplatin/Paclitaxel Induction Chemotherapy Followed By Standard Chemoradiation In HPV-Negative or High-risk HPV-Positive Locally Advanced Stage III/IVa/IVb HNSCC [NCT01732640]Phase 1/Phase 29 participants (Actual)Interventional2012-12-31Terminated(stopped due to Slow accrual and high levels of toxicity lead to early termination.)
Phase I Study of Accelerated Hypofractionated Radiation Therapy With Concomitant Chemotherapy for Unresectable Stage III Non-Small Cell Lung Cancer [NCT01486602]Phase 122 participants (Actual)Interventional2012-03-31Completed
Antioxidant Effects on the Outcome of Ovarian Cancer [NCT00228319]Phase 1/Phase 227 participants (Actual)Interventional2002-10-31Completed
A Phase II Study of Cetuximab (C225)/Paclitaxel/Carboplatin for the Initial Treatment of Advanced Stage Ovarian, Primary Peritoneal, and Fallopian Tube Cancer [NCT00063401]Phase 239 participants (Actual)Interventional2003-09-30Completed
Phase II Study of Carboplatin and Pemetrexed in Patients With Recurrent Platinum Sensitive Ovarian, Fallopian Tube or Primary Peritoneal Cancer [NCT00230542]Phase 244 participants (Actual)Interventional2005-09-30Completed
A Randomized Phase II Trial of Two Dose Schedules of Carboplatin/Paclitaxel/Cetuximab in Stage IIIB/IV Non-small Cell Lung Cancer [NCT00097227]Phase 2165 participants (Actual)Interventional2004-11-30Completed
Phase I Trial With Weekly Docetaxel, Capecitabine and Carboplatin as Induction Chemotherapy Followed by Concomitant Capecitabine and Radiotherapy in Patients With Locally Advanced Esophageal Cancer [NCT00238147]Phase 118 participants (Anticipated)Interventional2004-09-30Completed
A Phase II Study Of Preoperative Celecoxib/Paclitaxel/Carboplatin For Squamous Cell And Adenocarcinoma Of The Esophagus [NCT00066716]Phase 239 participants (Actual)Interventional2003-06-30Completed
Phase III Randomised Study Of Adjuvant Paclitaxel And Carboplatin (TAXOL-PARAPLATINE) With Concomittant Radiotherapy In Patients With Stage II or III Non-Metastatic Non-Small Cell Lung Cancer [NCT00077220]Phase 30 participants Interventional2002-06-30Active, not recruiting
Phase I Dose Finding Clinical Trial of Combination Paclitaxel, Carboplatin and Temozolomide for Subjects With Solid Tumor Malignancies. [NCT00249964]Phase 115 participants (Actual)Interventional2003-11-30Completed
Phase II Study of Weekly Irinotecan and Carboplatin in Extensive-Stage Small-Cell Lung Cancer [NCT00104793]Phase 255 participants (Anticipated)Interventional2003-06-30Completed
A Phase II, Randomized Study With Docetaxel-gemcitabine Followed by Radiotherapy vs Concomitant Treatment (Radiotherapy and Carboplatine-docetaxel) Followed by Docetaxel-gemcitabine Versus Docetaxel-gemcitabine Followed by Concomitant Treatment (Radiother [NCT00258739]Phase 2140 participants (Actual)Interventional2001-10-31Completed
Treatment of Stages IIIB and IV, Non Small Cell Lung Cancer With Alternating Cycles of Carboplatin/Taxol and Carboplatin/Gemcitabine. [NCT00259675]Phase 2100 participants (Anticipated)Interventional2004-05-31Completed
Induction Cisplatin/Irinotecan Followed By Combination Carboplatin, Etoposide And Chest Radiotherapy In Limited Stage Small Cell Lung Cancer: A Phase II Study [NCT00072527]Phase 278 participants (Actual)Interventional2003-11-30Completed
A Phase III Study of Delayed vs. Immediate Second-Line Therapy With Docetaxel After Gemcitabine + Carboplatin in Advanced Non-Small Cell Lung Cancer [NCT00074204]Phase 317 participants (Actual)Interventional2003-10-31Completed
A Phase I Study of Oral Capecitabine in Combination With Weekly IV Carboplatin/Paclitaxel and Radiation Therapy for Patients [NCT00281788]Phase 113 participants (Actual)Interventional2003-09-30Completed
Management of Children Aged Less Than 3 Years With Brain Tumors [NCT00281905]Phase 250 participants (Anticipated)Interventional1992-06-30Active, not recruiting
A Phase II Evaluation of Docetaxel and Carboplatin Followed by Tumor Volume Directed Pelvic Plus or Minus Para-Aortic Irradiation for Stage III/IV Endometrial Carcinoma [NCT00285415]Phase 246 participants (Actual)Interventional2005-04-30Terminated(stopped due to Investigator abruptly left Carilion.)
Protocol for Infants With Neuroblastoma Diagnosed Under the Age of One Year [NCT00287950]120 participants (Anticipated)Interventional1992-09-30Active, not recruiting
Feasibility Study of Neoadjuvant Chemotherapy Followed by Interval Cytoreductive Surgery for Stage III/IV Ovarian, Tubal and Peritoneal Cancers: JCOG0206 [NCT00112086]Phase 256 participants (Actual)Interventional2003-01-31Completed
A British Thoracic Oncology Group Phase III Trial of Gemcitabine Plus Cisplatin at 80mg/m Versus Gemcitabine Plus Carboplatin At 50 mg/m Versus Gemcitabine Plus Carboplatin AUC 6 in Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC) [NCT00112710]Phase 31,350 participants (Anticipated)Interventional2005-03-31Recruiting
Phase II Evaluation of Carboplatin, Paclitaxel and Bevacizumab as First Line Chemotherapy and Consolidation for Advanced Ovarian Cancer [NCT00129727]Phase 262 participants (Actual)Interventional2005-06-30Completed
A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of Intraperitoneal Carboplatin (NSC #214240) and Intravenous Paclitaxel (NSC # 673089) and Intravenous Paclitaxel, Intraperitoneal Carboplatin and NCI Supplied Intravenous B [NCT00079430]Phase 1113 participants (Actual)Interventional2004-06-30Completed
[NCT00086268]Phase 3250 participants (Actual)Interventional2004-04-30Completed
A Phase II Evaluation of Cetuximab (C225, NSC #714692) in Combination With Carboplatin (NSC #241240) in the Treatment of Recurrent Platinum-Sensitive Ovarian or Primary Peritoneal Cancer [NCT00086892]Phase 20 participants Interventional2004-06-30Completed
A Phase II Study Of Cetuximab (C225) In Combination With Chemoradiation In Patients With Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC) [NCT00081302]Phase 20 participants Interventional2004-03-31Completed
A Phase I Trial and Pharmacokinetic Study of Talabostat (PT-100, Val-Boro-Pro) in Combination With Temozolomide or Carboplatin in Pediatric Patients With Relapsed or Refractory Solid Tumors Including Brain Tumors [NCT00303940]Phase 126 participants (Anticipated)Interventional2005-12-31Completed
A Phase II Study of Neoadjuvant Therapy With Docetaxel, Carboplatin, and Bevacizumab in Patients With Resectable Early Stage Non-Small Cell Lung Cancer [NCT00293332]Phase 21 participants (Actual)Interventional2005-12-31Terminated(stopped due to Terminated due to low subject accrual)
A Phase II Trial of Irinotecan, Carboplatin, Bevacizumab in the Treatment of Patients With Extensive Stage Small Cell Lung Cancer [NCT00294931]Phase 250 participants (Anticipated)Interventional2006-02-28Completed
A Randomized Phase III Trial of Paclitaxel Plus Cisplatin Versus Paclitaxel Plus Carboplatin in Stage IVb, Persistent, or Recurrent Cervical Cancer (JCOG0505, CC-TPTC-P3) [NCT00295789]Phase 3253 participants (Actual)Interventional2006-02-28Completed
Cadonilimab (AK104) Plus Chemotherapy as First-line Treatment in Non-squamous Non-Small Cell Lung Cancer (NSCLC) Patients With Programmed Cell Death Ligand 1 (PD-L1) Negative：A Multi-center, Single-arm, Phase II Study [NCT06001151]Phase 249 participants (Anticipated)Interventional2023-08-07Recruiting
A Multicenter, Single-arm, Prospective Study of Neoadjuvant Pyrotinib Combined With Trastuzumab，Carboplatin and Paclitaxel for ER+/HER2+ Early or Locally Advanced Breast Cancer [NCT06000917]Phase 262 participants (Anticipated)Interventional2023-05-11Recruiting
A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of HLX26 (Anti-LAG-3 Monoclonal Antibody Injection) Combined With Serplulimab (Anti-PD-1 Humanized Monoclonal Antibody Injection) and Chemotherapy in Previously Untreated Advanced Non-smal [NCT05787613]Phase 260 participants (Anticipated)Interventional2023-07-10Recruiting
Older Non-Small Cell Lung Cancer Patients (>/= 70 Years of Age) Treated With First-Line MK-3475 (Pembrolizumab)+/- Chemotherapy (Oncologist's/Patient's Choice) [NCT04533451]Phase 2101 participants (Actual)Interventional2020-10-01Active, not recruiting
A Phase Ib/II, Open-Label Study of M7824 in Combination With Chemotherapy in Participants With Stage IV Non-small Cell Lung Cancer [NCT03840915]Phase 1/Phase 270 participants (Actual)Interventional2019-04-02Completed
A Phase 1/2 Randomized Trial of BMS-986012 in Combination With Platinum and Etoposide as First-line Therapy in Extensive-Stage Small Cell Lung Cancer [NCT02815592]Phase 112 participants (Actual)Interventional2016-11-28Active, not recruiting
"A Pilot Trial of Radiation Therapy Sandwiched Between Paclitaxel and Carboplatin in Patients With Uterine Carcinosarcoma" [NCT01367301]14 participants (Actual)Interventional2011-07-08Terminated(stopped due to Lack of accrual. PI left the institution)
A Phase II Study of Pembrolizumab, Lenvatinib and Chemotherapy Combination in First Line Extensive-stage Small Cell Lung Cancer (ES-SCLC) [NCT05384015]Phase 285 participants (Anticipated)Interventional2022-11-07Recruiting
Clinical Study of Neoadjuvant Anti-PD-1 Drug Toripalimab Combined With Chemotherapy in the Treatment of Primary Tracheal Squamous Cell Carcinoma [NCT04716751]Phase 215 participants (Anticipated)Interventional2021-02-01Not yet recruiting
Weekly Docetaxel and Carboplatin in Patients With Recurrent Squamous Carcinoma of the Cervix: A Phase I/II Study [NCT00084890]Phase 115 participants (Actual)Interventional2003-11-30Terminated(stopped due to slow accrual)
A Phase I Trial of Intravenous Paclitaxel, Intraperitoneal Carboplatin and Intraperitoneal Paclitaxel or Intravenous Docetaxel, Intraperitoneal Carboplatin and Intraperitoneal Paclitaxel or Intravenous Paclitaxel, Intraperitoneal Carboplatin, Intraperiton [NCT00085358]Phase 140 participants (Actual)Interventional2004-05-31Completed
Phase I Trial Testing the Safety and Tolerability of Chemoradiation Followed by Chemotherapy + Dostarlimab for Stage IIIC, Node Positive, Endometrial Cancer [NCT05819892]Phase 121 participants (Anticipated)Interventional2023-07-17Recruiting
A Randomized, Multicenter, Open-Label, Phase Ib Study to Evaluate Efficacy, Safety and Tolerability of IBI110 in Combination With Sintilimab Plus Etoposide and Platinum or Carboplatin in Patients With Untreated Extensive-Stage Small Cell Lung Cancer [NCT05026593]Phase 160 participants (Actual)Interventional2021-09-07Completed
A Phase I/II Trial of STA-4783 in Combination With Paclitaxel and Carboplatin for the Treatment of Chemotherapy Naive Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer (NSCLC) [NCT00088088]Phase 1/Phase 286 participants Interventional2004-03-31Completed
Phase 1-2a Dose-Ranging Study of the Triplet Combination of Carboplatin, Paclitaxel and TLK286 as First-Line Therapy in Advanced Non-Small Cell Lung Cancer [NCT00088556]Phase 1/Phase 2100 participants (Actual)Interventional2004-08-31Completed
Pelvic IMRT With Tomotherapy: A Phase I Feasibility Study in Post-Hysterectomy Endometrial Cancer Patients [NCT00334321]Phase 165 participants (Actual)Interventional2006-04-30Completed
Phase II, Randomized Study of Concomitant Chemoradiation Using Weekly Carboplatinum/Paclitaxel With (Arm A) or Without (Arm B) Daily Subcutaneous Amifostine in Patients With Newly Diagnosed Locally Advanced Squamous Cell Cancer of the Head and Neck [NCT00095927]Phase 258 participants (Actual)Interventional2003-05-31Completed
Neo-AEGIS (NEOadjuvant Trial in Adenocarcinoma of the oEsophagus and oesophagoGastric Junction International Study): Randomised Clinical Trial of Neoadjuvant and Adjuvant Chemotherapy (Modified MAGIC or FLOT Regimen) vs. Neoadjuvant Chemoradiation (CROSS [NCT01726452]Phase 3377 participants (Actual)Interventional2013-01-24Completed
Multicenter Randomized Phase III Study Comparing Docetaxel With Carboplatin Versus Docetaxel Single Agent as Second Line Treatment in Patients With Non-Small Cell Lung Cancer (NSCLC). [NCT00430651]Phase 3135 participants (Actual)Interventional2004-07-31Completed
A Phase II Trial of Carboplatin Plus Cetuximab for the Treatment of Stage IIIb/IV Non-Small Cell Lung Cancer [NCT00097214]Phase 257 participants (Actual)Interventional2004-11-30Completed
A Multicentre Phase III Randomized Double Blind Placebo Controlled Trial of Pravastatin Added to First-Line Standard Chemotherapy in Patients With Small Lung Cancer [NCT00433498]Phase 3846 participants (Actual)Interventional2007-01-31Completed
A Phase I, Open-Label, Dose-Escalation Study of the Safety and Tolerability of Ispinesib in Combination With Carboplatin on an Every 21-Day Schedule in Subjects With Advanced Solid Tumors. [NCT00136578]Phase 130 participants (Actual)Interventional2004-10-20Completed
A Phase II Study of Docetaxel Plus Carboplatin in Hormone Refractory Prostate Cancer Patients Refractory to Prior Docetaxel-based Chemotherapy [NCT00134706]Phase 230 participants (Actual)Interventional2004-01-31Completed
Phase II Trial of Docetaxel and Carboplatin Administered Every Two Weeks as Induction Therapy for Stage II or III Breast Cancer [NCT00107510]Phase 258 participants (Anticipated)Interventional2005-08-31Completed
Phase II Study of Weekly Paclitaxel, Carboplatin and Irinotecan in Patients With Advanced Non-Small Cell Lung Cancer Nad Malignant Pleural Effusion [NCT00465907]Phase 27 participants (Actual)Interventional2003-05-31Terminated(stopped due to Low accrual)
Phase I Trial of Induction Paraplatin® and Xeloda® Followed by Concurrent Paraplatin and Xeloda With Intensity Modulated Radiotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT00114153]Phase 148 participants (Anticipated)Interventional2003-06-30Completed
Evaluation of Activity and Toxicity of Polychemotherapy With 2-drug Combinations Containing Gemcitabine as First Line Treatment of Elderly Patients With Small Cell Lung Cancer [NCT00401609]Phase 1/Phase 285 participants Interventional2000-11-30Completed
A Phase I Trial of Dose Dense (Biweekly) Carboplatin Combined With Paclitaxel and Pegfilgrastim (Neulasta): A Feasibility Study in Patients With Untreated Stage III and IV Ovarian, Tubal or Primary Peritoneal Cancer [NCT00352300]Phase 143 participants (Actual)Interventional2006-06-30Completed
A Phase I Study of Vinblastine in Combination With Carboplatin for Children With Newly Diagnosed and Recurrent Low-Grade Gliomas [NCT00352495]Phase 126 participants (Actual)Interventional2006-06-30Completed
Carboplatin and Irinotecan Concomitantly With Radiation Therapy Followed by Consolidation Chemotherapy With Docetaxel for Locally Advanced Non-Small Cell Lung Cancer (GIA 12177). [NCT00449020]Phase 232 participants (Actual)Interventional2004-01-31Completed
Phase II Study of Weekly Neoadjuvant Chemotherapy Followed by Radical Chemoradiation for Locally Advanced Cervical Cancer [NCT00462397]Phase 250 participants (Anticipated)Interventional2005-06-30Recruiting
Perioperative Immunotherpay Versus Adjuvant Immunotherapy for Resectable Non-small Cell Lung Cancer [NCT06109402]Phase 2160 participants (Anticipated)Interventional2023-12-20Not yet recruiting
Phase II Study of Sequential Therapy With Paclitaxel Plus Carboplatin Followed by Gemzar Plus Carboplatin in the Treatment of Patients With Epithelial Ovarian Cancer FIGO Stages III-IV [NCT00490711]Phase 27 participants (Actual)Interventional2003-07-31Completed
Clinical Study of Programmed Cell Death Ligand-1(PD-L1) Antibody (Atezolizumab) Plus Chemotherapy (Carboplatin Plus Etoposide) for Previously Untreated Small Cell Lung Cancer [NCT04696939]Phase 2100 participants (Anticipated)Interventional2021-01-31Not yet recruiting
A Randomized, Double-Blind, Multicenter, Phase III Study to Compare Clinical Efficacy and Safety of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody Injection) in Combination With Chemotherapy (Carboplatin-Etoposide) in Previously Untreated Pati [NCT04063163]Phase 3585 participants (Actual)Interventional2019-09-12Active, not recruiting
Phase 1/1b, Open-Label, Dose-Escalation and Expansion Study to Evaluate the Safety and Antitumor Activity of MEDI3617 as a Single-Agent or in Combination Therapy in Adult Subjects With Advanced Solid Tumors [NCT01248949]Phase 1162 participants (Actual)Interventional2010-10-31Completed
A Phase I Study Investigating the Combination of RAD001 With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML) [NCT01154439]Phase 111 participants (Actual)Interventional2010-10-31Completed
Phase II Trial of Paclitaxel, Carboplatin and Gemcitabine in Patients With Locally Advanced Transitional Cell Carcinoma of the Bladder [NCT00136175]Phase 268 participants (Actual)Interventional1999-11-30Completed
Phase II Trial of Weekly Docetaxel (Taxotere®) and Carboplatin as Initial Chemotherapy for Women With Ovarian Cancer and Similar Malignancies [NCT00138242]Phase 230 participants (Anticipated)Interventional2004-12-31Completed
A Modular Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ceralasertib in Combination With Cytotoxic Chemotherapy and/or DNA Damage Repair/Novel Anti-cancer Agents in Pati [NCT02264678]Phase 1/Phase 2466 participants (Anticipated)Interventional2014-10-31Recruiting
A Phase II Study of Adjuvant Postoperative Radiation With Cisplatin Followed by Carboplatin/Paclitaxel Chemotherapy Following Total Abdominal Hysterectomy/Bilateral Salpino-Oophorectomy (TAH/BSO) for Patients With Stage I, II and IIIa Malignant Mixed Meso [NCT00505492]Phase 24 participants (Actual)Interventional2002-02-28Terminated(stopped due to Slow accrual.)
A Phase II Efficacy Study of Chemo-Radiotherapy in PET Stage II and III Merkel Cell Carcinoma of the Skin [NCT01013779]Phase 243 participants (Actual)Interventional2009-12-31Completed
Docetaxel and Carboplatin for Patients With Metastatic, Castration Resistant Prostate Cancer and Inactivated Genes in BRCA 1/2 Pathway [NCT02598895]Phase 214 participants (Actual)Interventional2016-01-26Completed
A Phase II Clinical Study Evaluating the Safety and Efficacy of Camrelizumab Combined With Chemotherapy and Apatinib as First Line Treatment in Advanced or Metastatic Extrapulmonary Neuroendocrine Carcinomas（EP-NEC） [NCT05142865]Phase 230 participants (Anticipated)Interventional2022-01-14Not yet recruiting
A Phase Ⅲ Randomized Study of Mitomycin/Vindesine/Cisplatin Versus Irinotecan/Carboplatin Versus Paclitaxel/Carboplatin With Concurrent Thoracic Radiotherapy for Unresectable Stage Ⅲ Non-Small-Cell Lung Cancer [NCT00144053]Phase 3450 participants Interventional2001-04-30Completed
Randomized Phase III-Study in Stage IIIb and IV Non-Small-Cell Lung Cancer. Sequential Single-Agent vs. Double-Agent vs. Triple-Agent Therapy. [NCT00148395]Phase 3280 participants Interventional2002-06-30Completed
A Randomized, Double-blind, Parallel-controlled Study Comparing the Efficacy and Safety of Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection (SIBP04) and Bevacizumab Injection (Avastin) in Combination With Paclitaxel and Carboplatin Respective [NCT05318443]Phase 3512 participants (Actual)Interventional2020-04-17Completed
A Randomized Phase III Study of Immune Checkpoint Inhibition With Chemotherapy in Treatment-Naive Metastatic Anal Cancer Patients [NCT04444921]Phase 3205 participants (Anticipated)Interventional2020-11-17Recruiting
A Phase III, Randomized, Single-blind Study Comparing the Efficacy, Safety, and Immunogenicity of SIBP-01 and CN-Trastuzumab Combination With Docetaxel and Carboplatin in Patients With Early or Locally Advanced Her2 Positive Breast Cancer [NCT03989037]Phase 3580 participants (Actual)Interventional2019-06-27Completed
A Phase 1 Study of Oral Debio 0123 in Combination With Carboplatin in Patients With Advanced Solid Tumors [NCT03968653]Phase 195 participants (Anticipated)Interventional2019-07-30Recruiting
Randomized Phase 2 Clinical Trial of Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab + Neoantigen Vaccine Vs. Nab-Paclitaxel + Durvalumab (MEDI4736) + Tremelimumab in Patients With Metastatic Triple Negative Breast Cancer [NCT03606967]Phase 270 participants (Anticipated)Interventional2021-04-13Recruiting
A Phase 1b-2 Study to Evaluate Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Various Regimens of Erdafitinib in Subjects With Metastatic or Locally Advanced Urothelial Cancer [NCT03473743]Phase 1/Phase 2125 participants (Actual)Interventional2018-04-05Active, not recruiting
A Phase II/III Multicenter Study Evaluating the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring Actionable Somatic Mutations Detected in Blood (B-FAST: [NCT03178552]Phase 2/Phase 31,000 participants (Anticipated)Interventional2017-09-22Recruiting
Phase II Study of Irinotecan and Carboplatin in Metastatic or Relapsed Small-Cell Lung Cancer [NCT00387660]Phase 280 participants (Actual)Interventional2001-10-31Completed
Neoadjuvant Therapy Study Guided by Drug Screening in Vitro Patient-derived Tumor-like Cell Clusters for HER2 Positive Early Breast Cancer Patients [NCT04750122]Phase 1/Phase 246 participants (Anticipated)Interventional2021-03-28Recruiting
CEV With/Without Periocular Carboplatin Chemotherapy for Nonmetastatic Extraocular Retinoblastoma Carboplatin--A Single Center, Retrospective Study to Evaluate the Efficacy of Carboplatin in Subjects With Retinoblastoma [NCT02319486]Phase 426 participants (Actual)Interventional2009-01-31Completed
A Multi-Center and Randomized Control Trial of Cisplatin, Carboplatin, Oxaliplatin, Docetaxel and Gemcitabine Plus Surgery as Treatment for Relapsed and Refractory Non-Small Cell Lung Cancer [NCT02889666]Phase 1500 participants (Anticipated)Interventional2008-01-31Recruiting
Phase I/II Study of Combined Chemotherapy and High Dose, Accelerated Proton Radiation for the Treatment of Locally Advanced Non-Small Cell Lung Carcinoma [NCT00614484]Phase 1/Phase 228 participants (Actual)Interventional1999-08-31Terminated(stopped due to Low participant enrollment rates. Significant comparative data not obtained.)
Phase II, Single-Arm Study of Low-Dose Radiotherapy (LDRT) Concurrent Cisplatin/Carboplatin Plus Etoposide With Serplulimab for Patients With Extensive-Stage Small Cell Lung Cancer [NCT05765825]Phase 261 participants (Anticipated)Interventional2023-03-25Not yet recruiting
A Phase Ib Open-Label Study of LB-100 in Combination With Carboplatin/Etoposide/Atezolizumab in Untreated Extensive-Stage Small Cell Lung Carcinoma [NCT04560972]Phase 121 participants (Anticipated)Interventional2021-05-28Recruiting
A Randomized, Phase II Study of Staggered, Chemo-Immunotherapy With Durvalumab, MEDI4736 Pemetrexed and Carboplatin (PC) for Metastatic Non-Squamous NSCLC [NCT04163432]Phase 284 participants (Anticipated)Interventional2020-06-16Recruiting
A Phase 1/2, Open-label, Multicenter Study of the Combination of NKTR-214 and Nivolumab or the Combination of NKTR-214, Nivolumab, and Other Anti-Cancer Therapies in Patients With Select Locally Advanced or Metastatic Solid Tumor Malignancies [NCT02983045]Phase 1/Phase 2557 participants (Actual)Interventional2016-12-19Completed
A Phase II Study of Docetaxel, Carboplatin With and Without Low Dose Radiation as Induction Therapy in Locally Advanced Head and Neck Cancer [NCT02126969]Phase 245 participants (Actual)Interventional2014-10-31Completed
Trial of Systemic Neoadjuvant Chemotherapy for Group B Intraocular Retinoblastoma [NCT00079417]Phase 328 participants (Actual)Interventional2005-12-26Completed
EGFR-TKI With/Without Chemotherapy in NSCLC Patients With Both EGFR Mutation and BIM Deletion Polymorphism [NCT03002844]Phase 250 participants (Anticipated)Interventional2016-12-31Not yet recruiting
Phase II Study of Irinotecan, Carboplatin, and Sunitinib in the First Line Treatment of Extensive-Stage Small Cell Lung Cancer [NCT00695292]Phase 237 participants (Actual)Interventional2008-06-30Completed
A Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed by Paclitaxel/Carboplatin Chemotherapy in Patients With High Risk, Early Stage Endometrial Carcinoma [NCT00807768]Phase 3601 participants (Actual)Interventional2009-03-23Active, not recruiting
Phase II Safety Study of Docetaxel and Carboplatin in Combination With Trastuzumab and Lapatinib in Early Breast Cancer [NCT00820872]Phase 230 participants (Actual)Interventional2009-02-28Completed
Phase II Study of Neoadjuvant Ixabepilone/Carboplatin/Trastuzumab in HER2-Positive Locally Advanced Breast Cancer [NCT00821886]Phase 260 participants (Actual)Interventional2009-02-28Completed
Randomized Phase II Trial of Pemetrexed vs. Pemetrexed/Bevacizumab vs. Pemetrexed/Carboplatin/Bevacizumab in Patients With Stage IIIB/IV Non-Small-Cell Lung Cancer and ECOG Performance Status 2 [NCT00892710]Phase 2172 participants (Actual)Interventional2009-06-30Completed
A Phase II Trial of Panitumumab, Gemcitabine, and Carboplatin in Triple-Negative Metastatic Breast Cancer [NCT00894504]Phase 271 participants (Actual)Interventional2010-02-28Completed
Electrochemotherapy With Carboplatinum Plus Bleomycin Versus Bleomycin Alone in Vulvar Cancer: the ElechtraPlatinum Study. A Randomized Controlled Trial [NCT05395962]Phase 292 participants (Anticipated)Interventional2022-04-08Recruiting
Phase I/II Study of Carboplatin and Pralatrexate in Patients With Recurrent Platinum-Sensitive Ovarian, Fallopian or Primary Peritoneal Cancer [NCT01188876]Phase 1/Phase 250 participants (Actual)Interventional2010-08-31Completed
Phase II Study of Neoadjuvant Immune Biomarker Modulation With Cetuximab Followed by Adjuvant Therapy With Concurrent Chemoradiotherapy or Radiotherapy With or Without Cetuximab for Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT01218048]Phase 240 participants (Actual)Interventional2011-02-28Completed
A 2-arm Randomized Phase II Study of Carboplatin, Paclitaxel Plus Reovirus Serotype-3 Dearing Strain (Reolysin) vs. Carboplatin and Paclitaxel in the First Line Treatment of Patients With Recurrent or Metastatic Pancreatic Cancer [NCT01280058]Phase 273 participants (Actual)Interventional2010-12-31Completed
Phase II Randomized Study of Vorinostat or Placebo in Combination With Carboplatin and Paclitaxel for Patients With Advanced Non-small Cell Lung Cancer [NCT01413750]Phase 1/Phase 223 participants (Actual)Interventional2010-11-30Terminated(stopped due to Slow Accrual)
A Phase 3 Randomized, Open-Label, Study of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for First-line Treatment of Advanced or Recurrent Endometrial Carcinoma (LEAP-001) [NCT03884101]Phase 3842 participants (Actual)Interventional2019-04-11Active, not recruiting
Treatment of Atypical Teratoid/Rhabdoid Tumors (AT/RT) of the Central Nervous System With Surgery, Intensive Chemotherapy, and 3-D Conformal Radiation [NCT00653068]Phase 370 participants (Actual)Interventional2008-12-08Active, not recruiting
A Pilot Phase II Trial Of Irinotecan Plus Carboplatin, And Irinotecan Maintenance Therapy (High-Risk Patients Only), Integrated Into The Upfront Therapy Of Newly Diagnosed Patients With Intermediate - And High-Risk Rhabdomyosarcoma [NCT00077285]Phase 265 participants (Anticipated)Interventional2003-10-31Active, not recruiting
A Prospective, Randomized, Open-label, Phase III Trial of Chemotherapy With Carboplatin And Paclitaxel, Versus Carboplatin And Paclitaxel In Combination With ISIS-3521, An Antisense Inhibitor Of Protein Kinase C Alpha In Patients With Advanced, Previously [NCT00017407]Phase 30 participants Interventional2000-10-13Completed
Trial Protocol for the Treatment of Children With High Risk Neuroblastoma (NB2004-HR) [NCT00526318]360 participants (Anticipated)Interventional2007-01-31Recruiting
Prospective, Non-randomised Phase 2 Clinical Trial of Carboplatin Plus Paclitaxel With Sequential Radical Pelvic Radiotherapy for Uterine Serous Papillary Cancer [NCT00147680]Phase 230 participants (Anticipated)Interventional2004-09-30Completed
Phase II Trial of Lazertinib+Pemetrexed/Carboplatin in Patients With EGFR Sensitizing Mutation Positive Recurrent or Metastatic Non-Small Cell Lung Cancer Failed to Prior Lazertinib (LUCAS) [NCT05786430]Phase 287 participants (Anticipated)Interventional2023-03-31Not yet recruiting
Multi-national, Randomized, Phase III, GCIG Intergroup Study Comparing Pegylated Liposomal Doxorubicin (CAELYX) and Carboplatin vs. Paclitaxel and Carboplatin in Patients With Epithelial Ovarian Cancer in Late Relapse. (CALYPSO) [NCT00538603]8 participants (Actual)Interventional2005-06-30Completed
A Pilot Study of Tamoxifen, Carboplatin and Topotecan in the Treatment of Recurrent or Refractory Primary Brain or Spinal Cord Tumors or Metastatic Epithelial Cancers With Central Nervous System Metastases [NCT00541138]Phase 250 participants (Anticipated)Interventional2003-05-31Completed
A Randomized Phase III Trial of Paraplatin (Carboplatin) + Gemzar Versus Gemzar Alone in Patients With Advanced Non-Small Cell Lung Cancer [NCT00190710]Phase 3242 participants Interventional2004-03-31Completed
A Phase 1 Study of MK-5890 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors [NCT03396445]Phase 1202 participants (Anticipated)Interventional2018-02-18Active, not recruiting
A Phase II/III Study of Paclitaxel/Carboplatin Alone or Combined With Either Trastuzumab and Hyaluronidase-oysk (HERCEPTIN HYLECTA) or Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf (PHESGO) in HER2 Positive, Stage I-IV Endometrial Serous Carcinoma or Ca [NCT05256225]Phase 2/Phase 3525 participants (Anticipated)Interventional2022-11-16Recruiting
A Randomised Phase II/III Study to Compare the Combination of Carboplatin Plus Irinotecan Vs. the Combination of Carboplatin Plus Etoposide for SCLC in Extensive Disease Stage [NCT00168896]Phase 2/Phase 3286 participants Interventional2001-10-31Recruiting
Therapy for Children With Advanced Stage High Risk Neuroblastoma [NCT00186849]Phase 230 participants (Actual)Interventional1997-10-31Completed
Phase II Trial With Combination Chemotherapy Consisting of Pegylated Liposomal Doxorubicin (PLD) and Carboplatin in Malignant Gynecologic Tumour's [NCT00189410]Phase 2140 participants (Actual)Interventional2003-06-30Completed
A Phase I Study of Weekly Topotecan in Combination With Carboplatin in Two Different Schedules for Patients With Refractory and/or Advanced Solid Tumors [NCT00193583]Phase 118 participants Interventional2003-05-31Completed
A Prospective Randomized Trial of Neoadjuvant Chemotherapy and Surgery Versus Concurrent Chemoradiation Therapy in Patients With Stage IB2-IIB Squamous Carcinoma of the Uterine Cervix [NCT00193739]Phase 3635 participants (Actual)Interventional2003-09-04Active, not recruiting
Post-operative Concurrent Chemo-radiotherapy Versus Post-operative Radiotherapy in High-risk Cutaneous Squamous Cell Carcinoma of the Head and Neck [NCT00193895]Phase 3321 participants (Actual)Interventional2005-04-30Completed
Phase II Trial of Ifosfamide/Carboplatin/Etoposide/Rituxan Followed by Zevalin in the Treatment of Patients With Relapsed/Refractory Intermediate Grade B-Cell Lymphoma [NCT00193505]Phase 240 participants Interventional2003-10-31Completed
Sequential High-Dose Chemotherapy Combining Two Mobilization and Cyto-Reductive Treatments Followed by Three High-Dose Chemotherapy Regimens Supported by Autologous Stem Cell Transplantation [NCT00231582]Phase 250 participants (Actual)Interventional2004-09-30Completed
Phase II Evaluation of Weekly Docetaxel in Combination With Weekly Carboplatin in the Treatment of Recurrent Epithelial Ovarian Carcinoma [NCT00214058]Phase 236 participants Interventional2002-08-31Completed
Phase II of Toripalimab Chemoradiotherapy in Neoadjuvant Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: A Single-center、Open Lable、Single-arm Exploratory Clinical Research [NCT04644250]Phase 232 participants (Anticipated)Interventional2020-09-01Recruiting
Neoadjuvant Treatment and Molecular Characterization of Locally Advanced Breast Cancer [NCT00068341]Phase 274 participants (Actual)Interventional2003-07-31Completed
A Phase 3, Open-label, Randomized Study of Nivolumab Combined With Ipilimumab, or With Standard of Care Chemotherapy, Versus Standard of Care Chemotherapy in Participants With Previously Untreated Unresectable or Metastatic Urothelial Cancer [NCT03036098]Phase 31,290 participants (Anticipated)Interventional2017-03-24Active, not recruiting
A Phase I Trial to Evaluate ZD1839(Iressa™) and Concurrent Chemo-Radiation in Patients With Locally Advanced Non Small Cell Lung Cancer [NCT00252798]Phase 144 participants Interventional2002-07-31Completed
Phase I Trial of Three-Weekly Docetaxel, Carboplatin and Oral CC-5013 in Patients With Advanced Solid Tumors [NCT00415116]Phase 114 participants (Actual)Interventional2004-08-31Completed
A Feasibility Study of Integrated Delivery of Hypofractionated Pelvic IMRT With Carboplatin and Paclitaxel in Stage III Copy-Number Low and Copy-Number High Subtypes of Endometrial Cancer [NCT05691010]Early Phase 128 participants (Anticipated)Interventional2023-01-10Recruiting
Pemetrexed Plus Gemcitabine Or Carboplatin In Patients With Advanced Malignant Mesothelioma: A Randomized Phase II Trial [NCT00101283]Phase 232 participants (Actual)Interventional2006-02-23Completed
Phase II Study of Gemcitabine, Carboplatin and VELIPARIB (ABT-888) in Refractory Testicular Germ Cell Cancer [NCT02860819]Phase 215 participants (Actual)Interventional2016-08-01Completed
Feasibility of Carboplatin, Paclitaxel and Bevacizumab Neoadjuvant Therapy for Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer [NCT01146795]Phase 232 participants (Actual)Interventional2010-05-17Completed
A Randomised, Double-blind, Placebo-controlled, Multicentre Phase Ш Clinical Study to Evaluate the Efficacy and Safety of First-line Treatment With SG001 Plus Chemotherapy±Bevacizumab Versus Placebo Plus Chemotherapy±Bevacizumab for PD-L1 Positive (CPS≥1) [NCT05715840]Phase 3368 participants (Anticipated)Interventional2023-01-31Not yet recruiting
A Phase 1B/2 Study of Taladegib in Combination With Weekly Paclitaxel, Carboplatin, and Radiation in Localized Adenocarcinoma of the Esophagus or Gastroesophageal Junction [NCT02530437]Phase 1/Phase 27 participants (Actual)Interventional2017-03-07Terminated(stopped due to The sponsor sold the drug TALADEGIB to another company during the trial and thereafter no drug was available. The sponsor made a decision to stop development of this drug Taladegib.)
Risk-adapted Therapy in HPV+ Oropharyngeal Cancer Using Circulating Tumor (ct)HPV DNA Profile - The ReACT Study [NCT04900623]Phase 275 participants (Anticipated)Interventional2021-07-02Recruiting
The NUVOLA TRIAL: Neoadjuvant Chemotherapy in Unresectable oVarian Cancer With OLAparib and Weekly Carboplatin Plus Paclitaxel: A Phase II Open-label Multicentre Study [NCT04261465]Phase 235 participants (Anticipated)Interventional2019-12-01Recruiting
Phase II Trial of RAD001 Plus Carboplatin in Patients With Triple-Negative Metastatic Breast Cancer [NCT01127763]Phase 225 participants (Actual)Interventional2010-06-30Completed
A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of INCMGA00012, an Anti-PD-1 Antibody, in Combination With Chemoradiation in Participants With Unresectable, Stage III Non-Small Cell Lung Cancer (POD1UM-301) [NCT04203511]Phase 30 participants (Actual)Interventional2020-07-31Withdrawn(stopped due to Sponsor Strategic/Business Decision)
Prospective Therapeutic De-escalation and miRNA-M371 Biomarker Evaluation Phase II Study for Stage IIa/IIb < 3 cm Seminomas [NCT05529251]Phase 290 participants (Anticipated)Interventional2022-09-06Recruiting
Phase-I Study of Bortezomib (VELCADE) Plus ICE (Ifosfamide, Carboplatin, Etoposide) for Patients With Relapsed Classical Hodgkin Lymphoma [NCT00439361]Phase 114 participants (Actual)Interventional2007-02-28Completed
A Randomized (PhaseII), Double-blind, Multicenter Phase I/II Trial of Pemetrexed, Carboplatin Plus or Minus Sorafenib in the First-line Treatment of Patients With Stage IIIb or IV Non-Small Cell Lung Cancer [NCT00473486]Phase 1/Phase 212 participants (Actual)Interventional2007-05-31Terminated(stopped due to Sorafenib administered in the combination with pemetrexed-carboplatin appears to enhance thrombocytopenia compared to historical data.)
ICON7 - A Randomised, Two-Arm, Multi-Centre Gynaecologic Cancer InterGroup Trial of Adding Bevacizumab to Standard Chemotherapy (Carboplatin and Paclitaxel) in Patients With Epithelial Ovarian Cancer [NCT00483782]Phase 31,520 participants (Anticipated)Interventional2006-04-30Completed
A Randomized Phase 3 Study of Datopotamab Deruxtecan (Dato-DXd) and Pembrolizumab With or Without Platinum Chemotherapy in Subjects With No Prior Therapy for Advanced or Metastatic PD-L1 TPS <50% Non-squamous Non-small Cell Lung Cancer Without Actionable [NCT05555732]Phase 3975 participants (Anticipated)Interventional2023-01-11Recruiting
Standard Infusion Carboplatin Versus Prophylactic Extended Infusion Carboplatin in theTreatment of Patients With Recurrent, Ovary, Fallopian Tube, and Primary Peritoneal Cancer [NCT01248962]Phase 2146 participants (Actual)Interventional2010-11-30Completed
A Single-arm, Exploratory Clinical Study of Envafolimab Combined With Chemotherapy in Neoadjuvant Therapy for Resectable Esophageal Squamous Cell Carcinoma [NCT05552651]Phase 240 participants (Anticipated)Interventional2022-09-20Not yet recruiting
Phase I/II Study of Paclitaxel / Carboplatin / RAD001 as First Line Therapy for Advanced Adenocarcinoma of the Stomach [NCT01514110]Phase 1/Phase 235 participants (Actual)Interventional2008-01-23Completed
An Open-label, Multicenter Phase II Clinical Trial of SHR-1701 With or Without Chemotherapy in the Treatment of Unresectable Stage III Non-small Cell Lung Cancer [NCT04580498]Phase 2107 participants (Actual)Interventional2020-11-10Active, not recruiting
Phase II Study of Weekly Paclitaxel/Carboplatin in Combination With Prophylactic G-CSF in the Treatment of Gynaecological Cancers [NCT01523678]Phase 2108 participants (Actual)Interventional2012-02-29Completed
Pilot Study of Correlation Between Molecular Phenotype and Response to Two Independent Treatment Regimens, Carboplatin and Paclitaxel vs. 5-Fluorouracil and Oxaliplatin Chemotherapy in Patients With Localized Esophageal Adenocarcinoma [NCT02392377]Phase 21 participants (Actual)Interventional2015-02-28Terminated(stopped due to Slow accrual)
Phase II Trial of Pulsed Dose Chemotherapy Plus Pembrolizumab in the First Line Treatment of Recurrent/Metastatic HNSCC [NCT06052839]Phase 215 participants (Anticipated)Interventional2023-09-30Not yet recruiting
A Multicenter, Double-blind, Randomized, Parallel-group, Phase 3 Study to Compare the Efficacy and Safety of the Proposed Biosimilar PERT-IJS and EU-Perjeta® Along With Trastuzumab and Chemotherapy (Carboplatin and Docetaxel) as Neoadjuvant Treatment in P [NCT06038539]Phase 3382 participants (Anticipated)Interventional2023-12-15Not yet recruiting
A Phase Ia/Ib Open-Label, Dose-Escalation Study of the Safety and Pharmacokinetics of Tiragolumab as a Single Agent and in Combination With Atezolizumab and/or Other Anti-Cancer Therapies in Patients With Locally Advanced or Metastatic Tumors [NCT02794571]Phase 1518 participants (Actual)Interventional2016-05-23Active, not recruiting
A Phase 1b Study of Ensartinib in Combination With Platinum-Based Chemotherapy and Bevacizumab in ALK-Positive Non-Small Cell Lung Cancer (NSCLC) [NCT04837716]Phase 112 participants (Anticipated)Interventional2021-03-18Active, not recruiting
A Phase III Randomized Trial for the Treatment of Newly Diagnosed Supratentorial PNET and High Risk Medulloblastoma in Children < 36 Months Old With Intensive Induction Chemotherapy With Methotrexate Followed by Consolidation With Stem Cell Rescue vs. [NCT00336024]Phase 391 participants (Actual)Interventional2007-08-06Active, not recruiting
A Phase I Dose Escalation Study of Eribulin in Combination With Weekly Carboplatin for the Treatment of Metastatic Breast Cancer [NCT01795586]Phase 119 participants (Actual)Interventional2013-02-06Completed
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Study to Evaluate the Efficacy of Paclitaxel-Carboplatin Alone or With Pegylated Endostatin for Advanced Non-small Cell Lung Cancer [NCT01527864]Phase 2300 participants (Anticipated)Interventional2011-05-31Recruiting
Multicenter Exploratory Trial of the Safety and Efficacy of Adjuvant Docetaxel and Carboplatin in Patients With Resected Non-small Cell Lung Cancer [NCT00883675]Phase 4133 participants (Actual)Interventional2009-05-31Completed
A Phase I Study of Continuous Endostar Intravenous Infusion Combined With Pemetrexed and Carboplatin in Advanced NSCLC Patients [NCT01531790]Phase 119 participants (Actual)Interventional2011-09-30Completed
Beamion LUNG-2: A Phase III, Open-label, Randomized, Active-controlled, Multi-centre Trial Evaluating Orally Administered BI 1810631 Compared With Standard of Care as First-line Treatment in Patients With Unresectable, Locally Advanced or Metastatic Nonsq [NCT06151574]Phase 3270 participants (Anticipated)Interventional2024-01-15Not yet recruiting
Pediatric Phase I Trial of RMP-7 and Carboplatin in Brain Tumors [NCT00001502]Phase 130 participants Interventional1996-04-30Completed
A Phase I Combination of Pazopanib and Carboplatin in Advanced Solid Malignancies [NCT01542047]Phase 13 participants (Actual)Interventional2012-08-31Terminated(stopped due to Low rate of accrual)
Phase II Trial of Neoadjuvant Chemotherapy for HPV-Associated Squamous Cell Carcinoma of the Oropharynx Followed by Reduced Dose Radiotherapy/Chemoradiotherapy for Responders or Standard Dose Chemoradiotherapy for Non-Responders [NCT01525927]Phase 22 participants (Actual)Interventional2010-08-31Terminated(stopped due to Principal Investigator left institution. IRB approval lapsed.)
Phase II Study of High Dose Cyclophosphamide, Mitoxantrone, and Carboplatin With Autologous Bone Marrow Transplantation in Refractory or Relapsed Ovarian Carcinoma [NCT00002474]Phase 20 participants Interventional1991-02-28Completed
A Randomized, Open Label, Controlled Study About Endostar Continued Pumping or Injecting Into Vein Combining With Gemcitabine-Carboplatin Versus Gemcitabine-Carboplatin Alone to Treat Non-Small Cell Lung Cancer (NSCLC) [NCT01549093]Phase 290 participants (Anticipated)Interventional2011-08-31Recruiting
Assessment of Feasibility and Safety of the Addition of ZD6474 (Zactima) to Carboplatin and Paclitaxel Administered Neo-Adjuvantly in Stage IB, II and T3, N1 Non-Small Cell Lung Cancer (NSCLC) [NCT00459121]Phase 22 participants (Actual)Interventional2007-07-31Terminated
A Multi-center, Open-Label, Adaptive, Randomized Study of Palifosfamide-tris, a Novel DNA Crosslinker, in Combination With Carboplatin and Etoposide (PaCE) Chemotherapy Versus Carboplatin and Etoposide (CE) Alone in Chemotherapy Naïve Patients With Extens [NCT01555710]Phase 3548 participants (Anticipated)Interventional2012-05-31Active, not recruiting
SCOTROC 4: A Prospective, Multicentre, Randomised Trial Of Carboplatin Flat Dosing Vs Intrapatient Dose Escalation In First Line Chemotherapy Of Ovarian, Fallopian Tube And Primary Peritoneal Cancers [NCT00098878]Phase 31,300 participants (Anticipated)Interventional2004-03-31Completed
A Randomized Phase III Study for the Treatment of Recurrent Epithelial Ovarian Cancer: Chemotherapy Alone Versus Chemotherapy Followed by Secondary Cytoreductive Surgery in Patients With a Treatment-Free Interval of More Than 12 Months [NCT00006356]Phase 338 participants (Actual)Interventional2000-08-31Terminated(stopped due to low accrual)
Phase II Study of Sequential Administration of Doxorubicin, Paclitaxel, and Carboplatin in Patients With Advanced and Recurrent Endometrial Cancer [NCT00006377]Phase 20 participants Interventional2000-06-30Completed
Phase III Randomized Study of TLK286 (Telcyta) in Combination With Carboplatin (Paraplatin) Versus Liposomal Doxorubicin (Doxil) as Second-Line Therapy in Platinum Refractory or Resistant Ovarian Cancer [ASSIST-3] [NCT00102973]Phase 3244 participants (Actual)Interventional2004-12-31Completed
A Phase I, Open-Label, Study of the Safety, Tolerability, and Pharmacokinetics of Pazopanib in Combination With Paclitaxel on a Weekly Schedule for Three Consecutive Weeks of a 28-Day Cycle, Paclitaxel and Carboplatin on an Every 21 Days Schedule and Lapa [NCT00388076]Phase 186 participants (Actual)Interventional2006-04-28Completed
A Phase II Trial of PS-341 in Combination With Paclitaxel and Carboplatin for Metastatic Adenocarcinoma of the Lower Esophagus, Gastroesophageal Junction, and Gastric Cardia [NCT00107341]Phase 237 participants (Actual)Interventional2005-08-31Completed
A Phase I/II Study of Carboplatin / Paclitaxel / Suramin Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) [NCT00006929]Phase 282 participants (Anticipated)Interventional2000-09-30Completed
Phase II Multicentered Study of First-Line Chemotherapy for Advanced or Recurrent Endometrial Carcinoma With the Combination of Carboplatin and Liposomal Doxorubicin [NCT00401635]Phase 242 participants Interventional2002-11-30Completed
Phase II Multicenter Study of the Combination of Weekly Carboplatin and Paclitaxel as First-line Chemotherapy for Elderly Patients With Ovarian Cancer. [NCT00401674]Phase 226 participants (Actual)Interventional2003-06-30Completed
A Phase II Trial of Ifosfamide, Carboplatin, and Etoposide (ICE) Chemotherapy in Combination With Rituximab as Salvage Therapy [NCT00007865]Phase 20 participants Interventional2000-09-01Completed
An Open-Label, Randomised Study of Multi-Cycle, Dose Intensive Carboplatin/Paclitaxel With Pegfilgrastim Supported by Haematopoietic Progenitor Cell Re-Infusion in Whole Blood [NCT00117442]Phase 261 participants (Actual)Interventional2002-08-31Completed
Phase I Evaluation Of Carboplatin And Gemcitabine [NCT00021346]Phase 18 participants (Actual)Interventional1997-11-30Completed
A Phase IIA Trial of Continuous Five Day Infusions of MSI-1256F (Squalamine Lactate) Plus Carboplatin for Therapy of Refractory and Resistant Stage III and IV Ovarian Cancer [NCT00021385]Phase 20 participants Interventional2001-05-31Active, not recruiting
Phase II Study of Carboplatin, Irinotecan, and Thalidomide in Patients With Advanced Non-Small Cell Lung Cancer [NCT00025285]Phase 246 participants (Actual)Interventional2001-11-01Completed
Clinical Correlative Studies In Primary Central Nervous System Germ Cell Tumors: The Third International CNS Germ Cell Tumor Study Group Protocol [NCT00025324]Phase 20 participants Interventional2000-12-31Active, not recruiting
MMT 98 Study For Metastatic Disease Rhabdomyosarcoma And Other Malignant Soft Tissue Sarcoma Of Childhood [NCT00025441]Phase 20 participants Interventional1998-11-30Completed
A Phase I Trial of Farnesyltransferase Inhibitor, R115777 (NSC # 702818) and Radiotherapy in Patients With Non-Small Cell Lung Cancer [NCT00025480]Phase 112 participants (Anticipated)Interventional2001-08-31Completed
European Infant Neuroblastoma Study - Unresectable Tumors (MYCN Not Amplified) [NCT00025597]Phase 20 participants Interventional1999-07-31Completed
A Phase I Study of PS-341 (NSC 681239), Carboplatin, and Etoposide in Patients With Advanced Solid Tumors Refractory to Standard Therapy [NCT00027898]Phase 127 participants (Actual)Interventional2002-01-31Completed
A Phase I Study of Epothilone B Analog BMS 247550 in Combination With Carboplatin in Recurrent and/or Refractory Solid Tumors [NCT00028561]Phase 145 participants (Actual)Interventional2001-10-31Terminated(stopped due to Administratively complete.)
Phase I Trial of Bortezomib (NSC 681239, IND#58443) and Carboplatin in Recurrent or Progressive Epithelial Ovarian Cancer or Primary Peritoneal Cancer [NCT00028912]Phase 10 participants Interventional2001-11-30Completed
A Phase II Study Of Paclitaxel, Carboplatin And Gemcitabine In Previously Untreated Patients With Epithelial Ovarian Carcinoma FIGO Stage IIB-IV [NCT00031954]Phase 2105 participants (Actual)Interventional2001-08-31Completed
Phase I/II Study Of Concurrent Chemotherapy And Escalating Doses Of Radiotherapy (RT) For Unresectable Non-Small Cell Lung Cancer (NSCLC) Using A New RT Paradigm [NCT00032032]Phase 169 participants (Actual)Interventional2002-05-31Completed
Induction/Concurrent Chemotherapy and Dose-Escalated Three Dimensional Thoracic Radiation for Patients With Stage III Non Small Cell Lung Cancer: A Randomized Phase II Study [NCT00033553]Phase 269 participants (Actual)Interventional2002-03-31Completed
Randomized Phase II/III Study Assessing Gemcitabine/Carboplatin And Methotrexate/Carboplatin/Vinblastine In Previously Untreated Patients With Advanced Urothelial Cancer Ineligible For Cisplatin Based Chemotherapy [NCT00014274]Phase 2/Phase 3238 participants (Actual)Interventional2001-01-31Completed
A Multicenter, Randomized Trial for Stage IIIB or IV NSCLC Comparing Weekly Taxol(Paclitaxel) and Carboplatin(Paraplatin) Regimen Versus Standard Taxol and Carboplatin Administered Every Three Weeks, Followed by Weekly Taxol. [NCT00035152]Phase 3444 participants Interventional2000-06-30Completed
A Phase 3 Randomized, Open-Label, Study of Pembrolizumab (MK-3475) Plus Lenvatinib (E7080/MK-7902) Versus Chemotherapy for First-line Treatment of Advanced or Recurrent Endometrial Carcinoma (LEAP-001) [NCT04865289]Phase 3875 participants (Anticipated)Interventional2019-10-22Active, not recruiting
A Phase 2 Trial of Antisense Nucleotide to PKC-Alpha (LY900003, ISIS 3521) Plus Gemcitabine and Carboplatin in Patients With Advanced, Previously Untreated Non-Small Cell Lung Cancer. [NCT00042679]Phase 20 participants Interventional2002-06-30Completed
A Phase I Study Of OSI-774 (NSC #718781)-Based Multimodality Therapy For Inoperable Stage III Non Small Cell Lung Cancer [NCT00042835]Phase 148 participants (Actual)Interventional2002-05-31Terminated(stopped due to Administratively complete.)
A Phase I/II Pilot Study of Patients With Brain Metastasis Secondary to Breast Cancer Treated With Methotrexate and Carboplatin in Conjunction With Blood-Brain Barrier Disruption, With Concurrent Trastuzumab in HER-2 Positive Patients [NCT00397501]Phase 1/Phase 20 participants (Actual)Interventional2013-10-31Withdrawn(stopped due to after original approval, IRB closed enrollment; major revisions required to re-open.)
A Phase II Clinical Trial of Tiragolumab in Combination With Carboplatin, Pemetrexed, and Atezolizumab in Patients With Non-squamous Non-small Cell Lung Cancer (NSCLC) and Untreated Brain Metastases [NCT05746481]Phase 235 participants (Anticipated)Interventional2023-08-08Recruiting
ALIMTA Plus Carboplatin as Front-Line Chemotherapy for Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer: A Phase 2 Clinical Trial. [NCT00051493]Phase 250 participants Interventional2002-04-30Completed
A Multi-National Randomized Phase-III GCIG Intergroup-Study Comparing 1st-line Chemotherapy With Gemcitabine/Paclitaxel/Carboplatin vs Paclitaxel/Carboplatin In Previously Untreated Patients With Epithelial Ovarian Cancer FIGO Stages I-IV [NCT00052468]Phase 31,742 participants (Actual)Interventional2002-08-31Completed
Phase II Study of Fludarabine, Carboplatin, and Topotecan With Thalidomide for Patients With Relapsed/Refractory or High Risk Acute Myelogenous Leukemia, Chronic Myeloid Leukemia and Advanced Myelodysplastic Syndromes [NCT00053287]Phase 242 participants (Actual)Interventional2002-09-30Completed
A Phase 1/1b Study to Evaluate the Safety and Tolerability of Immunotherapy Combinations in Participants With Lung Cancer [NCT03846310]Phase 177 participants (Actual)Interventional2019-04-01Active, not recruiting
Induction Chemotherapy for Locally Advanced Esophageal Cancer: A Phase II Study [NCT03110926]Phase 240 participants (Anticipated)Interventional2017-06-19Active, not recruiting
Parallel Phase II Trials of ZD1839 (Iressa) Alone or Weekly Carboplatin and Paclitaxel Followed by ZD1839 (Iressa) (Oncologists Must Choose) for Metastatic Non-Small Cell Lung Cancer in Patients > or = 65 Years of Age [NCT00062062]Phase 265 participants (Actual)Interventional2004-10-31Completed
A Randomized Double Blind Phase II Study of Preoperative Celecoxib/Paclitaxel/Carboplatin for Stage IIIA Non-Small Cell Lung Cancer [NCT00062179]Phase 27 participants (Actual)Interventional2003-03-31Completed
Phase II Clinical Trial to Evaluate the Preliminary Efficacy, Safety and Pharmacokinetic Characteristics of PM8002 Injection Combined With Standard Chemotherapy in the First-line Treatment of Subjects With Inoperable Malignant Mesothelioma [NCT05918107]Phase 255 participants (Anticipated)Interventional2022-08-13Recruiting
CT-2103/Carboplatin for Patients With Newly Diagnosed Stage III or IV Ovarian or Primary Peritoneal Cancer: A Phase 2 Study [NCT00069901]Phase 282 participants (Actual)Interventional2003-02-28Completed
Randomized Phase II Study of Eicosanoid Pathway Modulators and Cytotoxic Chemotherapy in Advanced Non-Small Cell Lung Cancer [NCT00070486]Phase 2140 participants (Actual)Interventional2003-12-31Completed
A Randomized, Partially Blinded, Phase II Study to Assess the Safety, Tolerability and Efficacy of ZD6474 Alone or in Combination With Paclitaxel and Carboplatin in Subjects With Previously Untreated Locally Advanced or Metastatic Non-small Cell Lung Canc [NCT00071188]Phase 20 participants Interventional2004-02-29Completed
A Randomized Feasibility Trial to Determine the Impact of Timing of Surgery and Chemotherapy in Newly Diagnosed Patients With Advanced Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Carcinoma [NCT00075712]Phase 2/Phase 3150 participants (Anticipated)Interventional2003-09-30Completed
A Phase II Trial of Gemcitabine, Carboplatin and PS-341 (NSC-681239) in the First-Line Treatment of Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00075751]Phase 299 participants (Actual)Interventional2004-01-31Completed
Intensified Pre-Operative Chemotherapy And Radical Surgery For High Risk Hepatoblastoma [NCT00077389]Phase 257 participants (Anticipated)Interventional2004-01-31Active, not recruiting
A Phase III Randomized Trial for the Treatment of Pediatric High Grade Gliomas at First Recurrence With a Single High Dose Chemotherapy and Autologous Stem Cell Transplant Versus Three Courses of Intermediate Dose Chemotherapy With Peripheral Blood Stem C [NCT00078988]Phase 31 participants (Actual)Interventional2004-10-31Completed
Dose Intensive Chemotherapy for Children Less Than Ten Years of Age Newly-Diagnosed With Malignant Brain Tumors: A Pilot Study of Two Alternative Intensive Induction Chemotherapy Regimens, Followed by Consolidation With Myeloablative Chemotherapy (Thiotep [NCT00392886]Phase 3120 participants (Anticipated)Interventional2004-03-31Active, not recruiting
Positron Emission Tomography Pre- and Post-treatment Assessment For Locally Advanced Non-Small Cell Lung Carcinoma [NCT00083083]Phase 2250 participants (Anticipated)Interventional2005-03-31Active, not recruiting
A Prospective,Multi-center, Open-labeled Phase 2 Randomized and Comparative Clinical Study of First Line Intermittent and Maintenance of Icotinib in Combination With Pemetrexed/Carboplatin Compared With Icotinib Single Drug in ⅢB/IV Non Small Cell Lung Ca [NCT03151161]Phase 2118 participants (Anticipated)Interventional2015-12-31Not yet recruiting
Randomized Study of ICE Plus RITUXIMAB Versus DHAP Plus Rituximab in Previously Treated Patients With Diffuse Large B-cell Lymphoma, Followed by Randomized Maintenance With Rituximab [NCT00137995]Phase 3481 participants (Actual)Interventional2003-06-30Completed
Phase II Selective Dose Escalation of Chemoradiotherapy for Esophageal Cancer [NCT00139633]Phase 225 participants Interventional2000-07-31Active, not recruiting
A Phase II Study of Cisplatin or Carboplatin for Triple-Negative Metastatic Breast Cancer and Evaluation of p63/p73 as a Biomarker of Response [NCT00483223]Phase 286 participants (Actual)Interventional2007-06-30Completed
A Phase 1-2 Study of Sirolimus, Docetaxel and Carboplatin for Treatment of Patients With Metastatic, Castration Resistant Prostate Cancer: (Rapamycin Inhibition of DDSP [RID]) [NCT02565901]Phase 1/Phase 228 participants (Actual)Interventional2016-02-29Terminated(stopped due to Terminated due to insufficient funding)
High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency [NCT01646034]Phase 374 participants (Actual)Interventional2014-09-30Active, not recruiting
Phase III Randomized Trial of Sequential High-Dose Chemotherapy Versus Standard Chemotherapy for the Treatment of Small Cell Lung Cancer [NCT00011921]Phase 3430 participants (Anticipated)Interventional1997-09-30Active, not recruiting
Multi-Cycle High-Dose Chemotherapy Versus Optimized Conventionally-Dosed Chemotherapy in Patients With Metastatic Breast Cancer: A Phase II Prospective Randomized Trial [NCT00012311]Phase 20 participants Interventional2000-01-31Active, not recruiting
Phase I/II Trial of Temozolomide and Carboplatin in Recurrent Glioblastoma Multiforme [NCT00014105]Phase 1/Phase 20 participants Interventional2000-12-31Active, not recruiting
Phase II Trial of Gemcitabine/Paraplatin® (Carboplatin) Followed by Taxol® (Paclitaxel) in Patients With Performance Status = 2,3 or Other Significant Co-Morbidity (HIV Infection or s/p Organ Transplantation) in Advanced Non-Small Cell Lung Cancer [NCT00276588]Phase 246 participants (Anticipated)Interventional2005-07-31Completed
Protocol for the Treatment of Extracranial Germ Cell Tumours in Children and Adolescents (GC III) [NCT00274950]Phase 3105 participants (Anticipated)Interventional2005-05-31Active, not recruiting
Neuroblastoma Study Phase II Study of Various Therapies in Patients With Neuroblastoma [NCT00017225]Phase 20 participants Interventional1997-05-31Completed
A Phase II Trial Of IM862 Combined With Paclitaxel And Carboplatin In Newly Diagnosed Advanced Epithelial Ovarian Or Primary Peritoneal Carcinoma Followed By IM862 Consolidation Therapy [NCT00017303]Phase 20 participants Interventional2001-01-31Active, not recruiting
Phase II Study of Calcitrol Enhanced Carboplatin in Hormone Refractory Prostate Cancer [NCT00017576]Phase 219 participants (Actual)Interventional2000-12-31Completed
A Phase II Trial of Intravenous Cereport (RMP-7) and Carboplatin in Childhood Brain Tumors [NCT00019422]Phase 20 participants Interventional1998-03-31Completed
Randomized Phase II/III Trial of Paclitaxel Plus Carboplatin With or Without Bevacizumab (NSC #704865) in Patients With Advanced Nonsquamous NSCLC [NCT00021060]Phase 2/Phase 3842 participants (Anticipated)Interventional2002-08-31Completed
Treatment Of Recurrent Central Nervous System Primitive Neuroectodermal Tumors (PNETs) In Children And Adolescents A Strategy Including The Use Of High Dose Thiotepa And High Dose Carboplatin [NCT00025077]Phase 250 participants (Anticipated)Interventional2000-01-31Completed
Phase II Study of Sequential Topotecan-Carboplatin-Etoposide in Patients With Extensive Stage Small Cell Lung Cancer [NCT00025272]Phase 214 participants (Actual)Interventional2001-11-01Completed
A Phase 2 Study Of Neoadjuvant rhuMAb VEGF (Bevacizumab) In Combination With Paclitaxel And Carboplatin In Surgically Resectable Non-Small Cell Lung Cancer [NCT00025389]Phase 28 participants (Actual)Interventional2001-11-30Completed
Treatment Of Children Over The Age Of 1 Year With Unresectable Localized Neuroblastoma Without MYCN Amplification [NCT00025428]Phase 3100 participants (Anticipated)Interventional2000-12-31Completed
European Infant Neuroblastoma Study - Stage 4 With Bone, Lung, Pleura or CNS Involvement; MYCN Not Amplified [NCT00025623]Phase 20 participants Interventional1999-07-31Completed
Chemotherapy and Atezolizumab for Patients With Extensive Stage Small Cell Lung Cancer (SCLC) With Untreated, Asymptomatic Brain Metastases [NCT04610684]Phase 23 participants (Actual)Interventional2021-01-05Active, not recruiting
A Phase 1b Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, for the Prevention of Chemotherapy-induced Myelosuppression [NCT04022876]Phase 135 participants (Actual)Interventional2019-09-03Terminated(stopped due to With a favorable safety profile the difference between treatment groups for the primary composite endpoint was not sufficient to generate statistically significant results with the targeted sample size)
A Phase I and Pharmacologic Study of the Proteasome Inhibitor PS-341 in Combination With Paclitaxel and Carboplatin in Patients With Advanced Malignancies [NCT00028587]Phase 196 participants (Actual)Interventional2001-12-31Completed
A Phase III Study of Cisplatin Plus Topotecan Followed by Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Carboplatin as First Line Chemotherapy in Women With Newly Diagnosed Advanced Epithelial Ovarian Cancer [NCT00028743]Phase 3819 participants (Actual)Interventional2001-08-31Completed
A Phase II Trial Of Adjuvant Chemotherapy For High Risk Transitional Cell Carcinoma Of The Urothelium [NCT00028860]Phase 20 participants Interventional2001-10-31Completed
A Phase III Randomized Trial Evaluating the Effect of Epoetin Alfa (Procrit) on Local Control in Patients Undergoing Concurrent Chemotherapy and Radiation Therapy for Non-Small Cell Lung Cancer [NCT00028938]Phase 31 participants (Actual)Interventional2002-01-01Completed
Paclitaxel/Topotecan/Etoposide (EtopoTax) Induction Followed by Consolidation Chemoradiotherapy for Limited Stage Small Cell Lung Cancer: A Phase II Study [NCT00033696]Phase 265 participants (Actual)Interventional2001-09-30Completed
A Phase 1 Study of UCN-01 in Combination With Carboplatin in Advanced Solid Tumors [NCT00036777]Phase 130 participants (Actual)Interventional2002-03-31Completed
Randomized Study of Radiotherapy in Patients With Stage 2B/3 (INSS) Neuroblastoma in Children Over 1 Year of Age [NCT00276731]Phase 30 participants Interventional1995-03-31Active, not recruiting
A Phase Ib, Open-Label, Multicohort Study of the Safety, Efficacy, and Pharmacokinetics of Tiragolumab in Combination With Atezolizumab and Chemotherapy in Patients With Triple-Negative Breast Cancer [NCT04584112]Phase 183 participants (Actual)Interventional2020-09-28Completed
ARIEL4 (Assessment of Rucaparib In Ovarian CancEr TriaL): A Phase 3 Multicenter, Randomized Study of Rucaparib Versus Chemotherapy in Patients With Relapsed, BRCA Mutant, High Grade Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer [NCT02855944]Phase 3349 participants (Actual)Interventional2017-03-01Completed
A Phase III, Open Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With a Platinum Agent (Cisplatin or Carboplatin) in Combination With Either Pemetrexed or Gemcitabine for PD-L1-Selected, Chemotherapy-Naive Patients With Stage IV No [NCT02409342]Phase 3572 participants (Actual)Interventional2015-07-20Completed
An Exploratory Phase II Clinical Trial of Anlotinib Combined With Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Cervical Cancer [NCT05772377]Phase 236 participants (Anticipated)Interventional2023-07-01Not yet recruiting
Induction Therapy With PD-1 Antibody Combined With Platinum-based Doublet Chemotherapy for Locally-advanced Non-small Cell Lung Cancer: A Randomised Controlled, Open-label, Phase 2 Trial [NCT05766800]Phase 2100 participants (Anticipated)Interventional2023-03-14Recruiting
An Open-Label Study of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of M4344 (Formerly VX-803) as a Single Agent and in Combination With Cytotoxic Chemotherapy in Participants With Advanced Solid Tumors [NCT02278250]Phase 197 participants (Actual)Interventional2015-01-26Completed
High Dose Chemotherapy and Autologous Peripheral Blood Stem Cell (PBSC) Rescue for Neuroblastoma: Standard of Care Considerations [NCT01526603]20 participants (Anticipated)Interventional2012-03-28Recruiting
Phase III Randomized Study of Paclitaxel and Carboplatin or Cisplatin Followed by Radiotherapy With or Without Concurrent Paclitaxel in Patients With Unresectable Stage III Non-Small Cell Lung Cancer [NCT00039039]Phase 3300 participants (Anticipated)Interventional2000-02-29Active, not recruiting
ZD1839 (NSC #715055, IND #61187) With Induction Paclitaxel And Carboplatin Followed By Either Radiation Or Concomitant Radiation With Weekly Paclitaxel And Carboplatin In Stage III Non-Small Cell Lung Cancer, A Phase II Study [NCT00040794]Phase 2144 participants (Actual)Interventional2002-05-31Completed
A Phase II Open-label, Randomized, Three-arm, Multicenter Study of LAG525 Given in Combination With Spartalizumab (PDR001), or With Spartalizumab and Carboplatin, or With Carboplatin, as First or Second Line Therapy in Patients With Advanced Triple-negati [NCT03499899]Phase 288 participants (Actual)Interventional2018-07-02Completed
N8: Dose-Intensive Chemotherapy Plus Biologics in the Treatment of Neuroblastoma [NCT00040872]Phase 20 participants Interventional2000-06-30Completed
A Phase I-II Trial Using Dendritic Cells Transduced With An Adenoviral Vector Containing The p53 Gene To Immunize Patients With Extensive Stage Small Cell Lung Cancer After Standard Chemotherapy [NCT00049218]Phase 1/Phase 256 participants (Actual)Interventional2003-04-30Completed
A Phase II Trial of Preoperative Radiation and Chemotherapy (Paclitaxel, Carboplatin, and Continuous Infusion 5-FU) for Locally Advanced Esophageal Cancer [NCT00022139]Phase 256 participants (Actual)Interventional2002-01-31Completed
A Phase II Activity And Safety Study Of IntraDose (Cisplatin/Epinephrine Injectable Gel) When Given In Combination With Systematic Chemotherapy Paclitaxel And Carboplatin In The Treatment Of Patients With Squamous Cell Carcinoma Of The Head And Neck At Fi [NCT00022217]Phase 20 participants Interventional2000-11-30Active, not recruiting
A Phase I Study Of Carboplatin And Irinotecan In Patients 1-21 Years Of Age With Refractory Solid Tumors [NCT00024284]Phase 10 participants Interventional2001-06-30Completed
A Phase I Study Of PS-341 In Combination With Gemcitabine And Carbloplatin In Selected Stage IIIB Or IV Non-Small Cell Lung Cancer [NCT00052338]Phase 134 participants (Actual)Interventional2002-09-30Completed
Protocol For The Treatment Of Relapsed And Refractory Wilms Tumour And Clear Cell Sarcoma Of The Kidney (CCSK) [NCT00025103]Phase 275 participants (Anticipated)Interventional2001-05-31Active, not recruiting
High Dose Carboplatin Combined With Oral VP-16 In The Treatment Of Pediatric CNS Malignancies [NCT00053118]Phase 11 participants (Actual)Interventional2002-03-31Completed
A Feasibility Study Of Primary Chemotherapy Followed By Concomitant Chemoradiation With And Without Amifostine In Patients With Locally Advanced Undifferentiated Nasopharyngeal Cancer (UNPC) [NCT00025298]Phase 25 participants (Actual)Interventional2001-07-31Terminated(stopped due to low accrual)
European Infant Neuroblastoma Study - Stage 4S and Stage 4 (No Bone, Lung, Pleura or CNS); MYCN Not Amplified [NCT00025610]Phase 20 participants Interventional1999-07-31Completed
European Infant Neuroblastoma Study - Stage 2, 3, 4, and 4S; MYCN Amplified Tumors [NCT00025649]Phase 20 participants Interventional1999-07-31Completed
CT-2103/Carboplatin vs Paclitaxel/Carboplatin for the Treatment of PS = 2 Patients With Chemotherapy Naive Advanced Non-Small Cell Lung Cancer (NSCLC): A Phase III Study [NCT00054210]Phase 30 participants Interventional2003-01-31Terminated
A Phase III Randomized, Open-Label Comparative Study of Induction Chemotherapy Followed by Thoracic Radiation Therapy With Supplemental Oxygen, With or Without Concurrent RSR13 (Efaproxiral), in Patients With Locally Advanced Unresectable (Stage IIIA/IIIB [NCT00055887]Phase 30 participants (Actual)Interventional2002-11-30Withdrawn(stopped due to Study never started. No patients were enrolled.)
A Pragmatic, Randomised Study To Compare The Hospitalisation Rates Of Two Platinum-Based Outpatient Regimens (Gemcitabine/Cisplatin vs. Gemcitabine/Carboplatin) In Non-Small Cell Lung Cancer (NSCLC) [NCT00055965]Phase 3400 participants (Anticipated)Interventional2002-11-30Active, not recruiting
Phase II Trial of Oral Topotecan and Intravenous Carboplatin With G-CSF (Filgrastim) Support in Previously Untreated Patients With Extensive Stage Small Cell Lung Cancer [NCT00028925]Phase 227 participants (Actual)Interventional2001-11-30Completed
A Phase II Study Of OSI-774 (NSC 718781) Given In Combination With Carboplatin In Patients With Recurrent Epithelial Ovarian Cancer [NCT00030446]Phase 250 participants (Actual)Interventional2002-01-10Completed
High Risk Neuroblastoma Study 1 Of Siop-Europe [NCT00030719]Phase 3175 participants (Anticipated)Interventional2001-12-31Recruiting
Single-Agent Versus Combination Chemotherapy in Advanced NSCLC: A CALGB Randomized Trial of Efficacy, Quality of Life, and Cost-Effectiveness [NCT00003117]Phase 3584 participants (Actual)Interventional1997-10-31Completed
A Phase II Study of Rituximab (IND #7028) and Ifosfamide, Carboplatin and Etoposide (ICE) Chemotherapy in Children With Recurrent/Refractory B-cell (CD20+) Non-Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia [NCT00058461]Phase 282 participants (Anticipated)Interventional2003-11-30Terminated
Phase I/II Trial, Dose Finding Combination Chemotherapy With PegLiposomal Doxorubicin (PLD) And Carboplatin In Patients With Gynecologic Tumors [NCT00032162]Phase 1/Phase 263 participants (Actual)Interventional2001-08-31Completed
Autologous Blood and Marrow Transplantation for Hematologic Malignancy and Selected Solid Tumors [NCT00060255]Phase 2451 participants (Actual)Interventional1991-12-31Completed
A Phase I Study Of Tirapazamine (NSC 130181) Paclitaxel And Carboplatin With Concurrent Radiation Followed By Tirapazamine/Paclitaxel/Carboplatin Consolidation For Stage III Non-Small Cell Lung Cancer [NCT00033410]Phase 130 participants (Anticipated)Interventional2002-03-31Completed
A Two Part, Multiple Dose Clinical Trial of the Safety and Efficacy of ABX-EGF in Combination With Paclitaxel and Carboplatin in Patients With Advanced Non-Small Cell Lung Cancer [NCT00034346]Phase 2194 participants Interventional2002-01-31Completed
Promune™ (CPG 7909 Injection) In Combination With Chemotherapy In Patients With Advanced Or Metastatic Non-Small Cell Lung Cancer, A Randomized, Multi-Center, Controlled, Phase 2 Study [NCT00070629]Phase 2116 participants (Actual)Interventional2003-05-31Completed
Phase II Study of Neoadjuvant Dose-Intensive Chemotherapy With Adriamycin and Ifosfamide Followed by High-Dose ICE in Locally Advanced Soft Tissue Sarcomas [NCT00204646]Phase 20 participants Interventional1999-02-28Completed
A Phase II Study of Carboplatin, Etoposide, and Exisulind in Patients With Extensive Small Cell Lung Cancer [NCT00041054]Phase 241 participants (Actual)Interventional2002-06-30Completed
[NCT00042302]Phase 3540 participants Interventional2002-06-30Terminated
A Phase III Study of Liposomal Doxorubicin Plus Carboplatin Versus Carboplatin in Platinum-Sensitive Patients With Recurrent Epithelial Ovarian and Peritoneal Carcinoma After Failure of Initial Platinum-Based Chemotherapy [NCT00043082]Phase 361 participants (Actual)Interventional2002-08-31Completed
A Randomized Phase II/III Trial Comparing Carboplatin-Ifosfamide (IC)-Chemotherapy Vs. IC-Chemotherapy Combined With Extreme Whole Body Hyperthermia In Patients With Recurrence Of Epithelial Ovarian Carcinoma: DOLPHIN-1-STUDY [NCT00045461]Phase 2/Phase 3241 participants (Anticipated)Interventional2000-06-30Recruiting
Study of Sequential Topoisomerase, Irinotecan/Oxaliplatin-Etoposide/Carboplatin in Extensive SCLC [NCT00240097]Phase 230 participants (Actual)Interventional2005-06-30Completed
Phase III Randomized Comparison Study of Vinorelbine, Gemcitabine, and Docetaxel Versus Paclitaxel and Carboplatin in Patients With Advanced Non-Small Cell Lung Cancer [NCT00079287]Phase 30 participants Interventional2001-03-31Completed
a Multicenter Clinical Trial for the Treatment of Children and Adolescents With Soft Tissue Sarcoma Stage 4 [NCT00130858]Phase 290 participants (Anticipated)Interventional2005-01-31Completed
Combined Phase I/II Study of Epirubicin (Pharmorubicin®), Carboplatin (Paraplatin®) and Capecitabine (Xeloda®) (ECC) in the Treatment of Unresectable Locally Advanced or Metastatic Gastric/Gastroesophageal Junction Cancer With Pharmacogenetic Correlates [NCT00130936]Phase 1/Phase 250 participants (Anticipated)Interventional2005-10-31Terminated
Nephroblastoma (Wilms Tumour) Clinical Trial And Study [NCT00047138]Phase 3350 participants (Anticipated)Interventional2001-01-31Recruiting
A Multicenter Phase III Randomized Trial Comparing Docetaxel (Taxotere) and Trastuzumab (Herceptin) With Docetaxel (Taxotere), Carboplatin and Trastuzumab (Herceptin) as First Line Chemotherapy for Patients With Advanced Breast Cancer Containing the HER2 [NCT00047255]Phase 3263 participants (Actual)Interventional2002-05-31Completed
Osteosarcoma 1999-A Study Of Intensive Chemotherapy Utilizing Ifosfamide, Carboplatin, and Doxorubicin for Adjuvant Chemotherapy for Treatment of Osteosarcoma [NCT00145639]Phase 280 participants (Actual)Interventional1999-05-31Completed
A Randomized Phase II Study Of Carboplatin And Etoposide With Or Without G3139 (NSC #683428, IND #58842) In Patients With Extensive Stage Small Cell Lung Cancer [NCT00042978]Phase 255 participants (Actual)Interventional2003-04-30Completed
A Phase II Trial Evaluating the Combination of Carboplatin, Gemcitabine, and Capecitabine in Patients With Carcinoma of Unknown Primary Site [NCT00148135]Phase 20 participants Interventional2001-05-31Terminated(stopped due to recruitment goals met)
A Single-arm Exploratory Clinical Study on the Efficacy and Safety of Toripalimab Combined With Bevacizumab, Nab-paclitaxel and Carboplatin for Untreated Metastatic Pulmonary Sarcomatoid Carcinoma [NCT04725448]Phase 227 participants (Anticipated)Interventional2021-04-06Recruiting
[NCT00049790]Phase 20 participants InterventionalCompleted
Phase I/Ib Trial of COmbined 5'aZacitidine and Carboplatin for Recurrent/Refractory Pediatric Brain and Solid Tumors [NCT03206021]Phase 131 participants (Actual)Interventional2017-08-01Active, not recruiting
Pilot Study for the Determination of Tumor Response to Chemotherapy in Advanced Non-Small Cell Lung Cancer Through Gene Expression Profiling. [NCT00161278]Phase 21 participants (Actual)Interventional2004-12-31Terminated(stopped due to recruitment has ended)
Combination of Paclitaxel, CisplatinCarboplatin With Toripalimab and Anlotinib for First Line Treatment of Advanced Cervical Cancer [NCT04731038]Phase 120 participants (Anticipated)Interventional2021-08-01Recruiting
Double Dose Intensive Chemo-Radiotherapy With Peripheral Blood Progenitor Cell Rescue for Children With Advanced Stage Neuroblastoma and Sarcomas [NCT00165139]Phase 220 participants (Actual)Interventional1996-01-31Completed
A Randomized, Phase III Multicenter Trial Of Gemcitabine In Combination With Carboplatin Or Paclitaxel Plus Carboplatin In Patients With Metastatic (Stage IIIB, IV) Non-Small Cell Lung Cancer [NCT00054392]Phase 30 participants (Actual)Interventional2001-09-30Withdrawn(stopped due to Not opened at Fox Chase Cancer Center)
A Phase I Dose Escalation Study of ABI-007 With Carboplatin TM as First-Line Therapy in Patients With Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma [NCT00407407]Phase 16 participants (Actual)Interventional2006-11-01Terminated(stopped due to MTD not determined)
Randomized Phase II Study to Determine the Efficacy of a Three Weekly vs. Weekly Therapy With Paclitaxel Plus Carboplatin vs. Paclitaxel Plus Vinorelbine for Patients With Non Small Cell Lung Cancer According to UICC Stage IIIB and IV [NCT00168883]Phase 280 participants Interventional2002-10-31Recruiting
Clinical Study of Toripalimab Combined With Anlotinib, Etoposide and Platinum in the Treatment of Extensive-stage Small Cell Lung Cancer [NCT04731909]80 participants (Anticipated)Interventional2018-10-01Recruiting
Phase II Evaluation of Carboplatin, Paclitaxel and Gemcitabine Followed by Concurrent Cisplatin and Radiation Therapy in Patients With Locally Advanced or Recurrent Urothelial Malignancy [NCT00055835]Phase 27 participants (Actual)Interventional2002-11-30Completed
A Multicenter, Open-Label, Parallel, Phase 2a Study of PLX2853 Monotherapy in Advanced Gynecological Malignancies With a Known ARID1A Mutation and Phase 1b/2a Study of PLX2853/Carboplatin Combination Therapy in Platinum-Resistant Epithelial Ovarian Cancer [NCT04493619]Phase 1/Phase 237 participants (Actual)Interventional2020-08-11Terminated(stopped due to study terminated due to business realignment)
Thalomid and Carboplatin for the Treatment of Pediatric Brain Stem Glioma [NCT00179881]Phase 247 participants (Anticipated)Interventional1999-12-31Completed
Chemotherapy Plus Local Surgical Treatment in Children With Intraocular Germ-Line Retinoblastoma [NCT00179920]Phase 230 participants Interventional1996-04-30Completed
Phase I Study of CCI-779 (NSC 683864) in Combination With Carboplatin and Paclitaxel in Patients With Advanced Solid Tumours [NCT00408655]Phase 138 participants (Actual)Interventional2007-02-28Completed
5-Fluorouracil-Leucovorin With or Without Carboplatin as Adjuvant Treatment for Primary Dukes B2-C Colon Cancer; Chronomodulated Versus Standard Administration. A Multicenter Randomized Phase III Trial of the GRECCR-Belgium (Study 03). [NCT00046995]Phase 3800 participants (Anticipated)Interventional2001-05-31Active, not recruiting
A Randomized, Double-Blind, Placebo-Controlled Phase 1b/2 Study of LY2228820, a p38 MAPK Inhibitor, Plus Gemcitabine and Carboplatin Versus Gemcitabine and Carboplatin for Women With Platinum-Sensitive Ovarian Cancer [NCT01663857]Phase 1/Phase 2118 participants (Actual)Interventional2012-07-31Completed
A Multi-National,Randomized, Phase III, GCIG Intergroup Study Comparing Pegylated Liposomal Doxorubicin and Carboplatin Versus Paclitaxel and Carboplatin in Patients With Epithelial Ovarian Cancer in Late Relapse (> 6 Months) [NCT00189553]Phase 3976 participants (Actual)Interventional2005-04-30Completed
A Phase I Study Evaluating the Safety and Tolerability of PS-341(Bortezomib)and Carboplatin in Patients With Platinum- and Taxane-Resistant Recurrent Ovarian Cancer, Primary Peritoneal Cancer, and Fallopian Tube Cancer [NCT00059618]Phase 121 participants (Actual)Interventional2003-04-30Completed
A Randomized Phase II Trial of Gemcitabine Containing Regimens (Gemcitabine/Carboplatin and Gemcitabine/ Cisplatin)When Used as Preoperative Chemotherapy for Patients With Stage I and II NSCLC [NCT00191230]Phase 270 participants Interventional2001-09-30Completed
Paclitaxel, Carboplatin, Infusional 5-Fluorouracil, and Radiation Therapy With or Without Surgical Resection in Locally Advanced Esophageal Cancer [NCT00193141]Phase 2200 participants Interventional1999-10-31Completed
A Phase II Study of a Three-Day Schedule of Topotecan Plus Paclitaxel and Carboplatin on Day Three in the Initial Treatment of Advanced Ovarian and Primary Peritoneal Carcinoma [NCT00193297]Phase 250 participants Interventional2002-02-28Completed
Phase II Study of Paclitaxel, Carboplatin, and Oral Etoposide Followed by Weekly Paclitaxel in the Treatment of High Grade Neuroendocrine Carcinoma [NCT00193531]Phase 2100 participants Interventional1998-12-31Completed
A Dose-Escalating Phase I Study With an Expanded Cohort to Assess the Feasibility of CT-2103 and Carboplatin (NSC #214240) in Patients With Previously Untreated Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Carcinoma [NCT00060359]Phase 132 participants (Actual)Interventional2003-04-30Completed
Three Modalities of Treatment in Operable and Resectable Stage IIIA (T1-3, N2) NSCLC. Randomized Phase II Study [NCT00198367]Phase 2120 participants (Actual)Interventional2003-01-31Completed
A Phase II Single-Arm Study Evaluating the Safety and Effectiveness of ABT-510 Plus Combination Chemotherapy in Subjects With Non-Small Cell Lung Cancer (NSCLC) [NCT00061646]Phase 225 participants (Actual)Interventional2003-03-31Terminated(stopped due to Enrollment suspended based upon interim analysis; subjects allowed to stay on study until disease progression.)
A Phase III Randomized, Double Blind, Placebo Controlled Trial Of Carboplatin/Etoposide With Or Without Thalidomide In Small Cell Lung Cancer (Study 12) [NCT00061919]Phase 3724 participants (Actual)Interventional2003-04-30Completed
Randomized Phase III Trial of Conventional Paclitaxel and Carboplatin Versus Dose Dense Weekly Paclitaxel and Carboplatin in Patients With Newly Diagnosed Stage II-IV Mullerian Carcinoma [NCT00226915]Phase 3637 participants (Actual)Interventional2003-04-30Completed
A Phase 1, Open-Label Dose Escalation First-in-Human Study to Evaluate the Tolerability, Safety, Maximum Tolerated Dose, Preliminary Clinical Activity and Pharmacokinetics of AM0010 in Patients With Advanced Solid Tumors [NCT02009449]Phase 1350 participants (Actual)Interventional2013-11-15Active, not recruiting
A Randomized Phase II Study of Paclitaxel/Carboplatin With or Without Sorafenib in the First-Line Treatment of Patients With Stage III/IV Epithelial Ovarian Cancer [NCT00390611]Phase 285 participants (Actual)Interventional2006-10-31Completed
A Phase II, Multicenter Trial of Gemcitabine, Carboplatin, and Sorafenib in Chemotherapy-naive Patients With Advanced/Metastatic Bladder Carcinoma [NCT00461851]Phase 217 participants (Actual)Interventional2007-03-31Completed
A Randomized, Open, Multicenter Phase 1/Phase 2 Clinical Trial of TQB2618 Injection Combined With Penpulimab Injection and Chemotherapy Versus Penpulimab Injection Combined With Chemotherapy in First-line Treatment of Relapsed/Metastatic Head and Neck Squ [NCT05783921]Phase 1/Phase 260 participants (Anticipated)Interventional2023-05-23Recruiting
Enhancing Immunotherapy by Targeting the EGFR Pathway in Inflammatory Breast Cancer: A Phase II Study of Panitumumab (PmAb) and Pembrolizumab (Pembro) in Combination With Neoadjuvant Chemotherapy (NAC) in Patients With Newly Diagnosed Triple Negative Infl [NCT05177796]Phase 20 participants (Actual)Interventional2022-03-11Withdrawn(stopped due to 0 participants recruited)
Feasibility and Safety of Neoadjuvant Nivolumab and Chemotherapy for Resectable Malignant Pleural Mesothelioma [NCT04162015]Phase 135 participants (Anticipated)Interventional2019-11-12Recruiting
A Phase I/III, Randomized, Double-Blind, Placebo-Controlled Study of Carboplatin Plus Etoposide With or Without Atezolizumab (Anti-PD-L1 Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer [NCT02763579]Phase 3503 participants (Actual)Interventional2016-06-07Completed
A Phase II Trial of Lamivudine in Combination With Chemoimmunotherapy in Patients With Extensive Stage SCLC [NCT04696575]Phase 228 participants (Anticipated)Interventional2021-07-02Recruiting
A Phase 2 Randomized Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC) [NCT04623775]Phase 2420 participants (Anticipated)Interventional2021-02-17Active, not recruiting
Intensified Chemo-immuno-radiotherapy With Durvalumab (MEDI4736) for Stage III Non-Small Cell Lung Cancers (NSCLCs): a Brazilian Single Arm Phase II Study (PACIFIC BRAZIL) [NCT04230408]Phase 248 participants (Anticipated)Interventional2021-03-05Active, not recruiting
High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors [NCT00936936]Phase 264 participants (Actual)Interventional2009-06-02Active, not recruiting
Randomized Phase II Trial of Adjuvant Carboplatin, Docetaxel, Bevacizumab, and Erlotinib Versus Chemotherapy Alone in Patients With Resected Non-Small Cell Lung Cancer [NCT00621049]Phase 2112 participants (Actual)Interventional2007-12-31Completed
Radiosensitization With a COX-2 Inhibitor (Celecoxib), With Chemoradiation for Cancer of the Head and Neck [NCT00581971]Phase 1/Phase 230 participants (Actual)Interventional2002-09-30Completed
A Phase II Study of Combination Therapy With Paclitaxel, Carboplatin and Megesterol Acetate for the Management of Advanced Stage or Recurrent Carcinoma of the Endometrium [NCT00584857]Phase 230 participants (Actual)Interventional2004-07-31Completed
Phase II Trial of Neoadjuvant Chemotherapy [NCT] With Weekly Nanoparticle Albumin-bound Paclitaxel [Nab-paclitaxel; Abraxane®] in Combination With Carboplatin and Bevacizumab in Women With Clinical Stages I-III Breast Cancer [NCT00675259]Phase 233 participants (Actual)Interventional2008-07-31Completed
A Study to Evaluate the Safety and the Efficacy of Transient Opening of the Blood-brain Barrier (BBB) by Low Intensity Pulsed Ultrasound With the SonoCloud-9 Implantable Device in Recurrent Glioblastoma Patients Eligible for Surgery and for Carboplatin Ch [NCT03744026]Phase 1/Phase 238 participants (Actual)Interventional2019-02-18Completed
Randomized Phase II Study of Cisplatin and Etoposide Versus Temozolomide and Capecitabine in Patients With Advanced G3 Non-small Cell Gastroenteropancreatic Neuroendocrine Carcinomas [NCT02595424]Phase 2126 participants (Anticipated)Interventional2016-04-06Recruiting
A Randomized Phase III Trial of IV Carboplatin (AUC 6) and Paclitaxel 175 mg/m2 Q 21 Days x 3 Courses Plus Low Dose Paclitaxel 40 mg/m2/wk Versus IV Carboplatin (AUC 6) and Paclitaxel 175 mg/m2 Q 21 Days x 3 Courses Plus Observation in Patients With Early [NCT00003644]Phase 3571 participants (Actual)Interventional1998-10-31Completed
A Study of the Effect of Anlotinib, Pemetrexed or the Combination As Maintenance Therapy for Patients With Non-Squamous Non-Small Cell Lung Cancer. [NCT04453423]Phase 290 participants (Anticipated)Interventional2020-07-01Not yet recruiting
Chemotherapy (Paclitaxel and Carboplatin)and Thoracic Radiotherapy With Swallowed Manganese Superoxide Dismutase (MnSOD) Plasmid Liposome Protection in Patients With Locally Advanced Stage III Non-Small Cell Lung Cancer: A Phase I-II Study [NCT00618917]Phase 1/Phase 218 participants (Actual)Interventional2005-11-11Terminated(stopped due to MnSOD longer available during Phase II)
Treatment Response and microRNA Profiles in Triple Negative Breast Cancer Patients Receiving Standard Chemotherapy [NCT04771871]Phase 242 participants (Anticipated)Interventional2021-11-29Recruiting
Phase 1 Study of Anti-HB-EGF Monoclonal Antibody KHK2866 as Monotherapy in Subjects With Advanced Solid Tumors and in Combination With Chemotherapy in Ovarian Cancer [NCT01279291]Phase 122 participants (Actual)Interventional2011-01-31Terminated(stopped due to The study was stopped due to the inability to determine an acceptable dose with the potential for further study)
Phase IIb Trial of Paclitaxel Plus Carboplatin Versus Paclitaxel Plus Epirubicin as Neoadjuvant Treatment in Locally Advanced Triple-negative Breast Cancer [NCT01276769]Phase 280 participants (Anticipated)Interventional2008-01-31Recruiting
ChemoRadiation And Tislelizumab for Esophageal/EGJ Cancer [NCT05245760]Phase 20 participants (Actual)Interventional2022-04-30Withdrawn(stopped due to Funding unavailable.)
A Phase II Study of Chemotherapy Treatment Based on Molecular Profiling Diagnosis for Patients With Carcinoma of Unknown Primary Site [NCT00737243]Phase 2289 participants (Actual)Interventional2008-08-31Completed
A Single-arm, Open-label, and Multicenter Phase Ⅱ Study Designed to Evaluate the Efficacy and Safety of Rulonilimab Combined With Chemotherapy in Patients With Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) [NCT05741021]Phase 284 participants (Anticipated)Interventional2023-03-01Not yet recruiting
A Phase Ib/II Study of Leronlimab (PRO 140) Combined With Carboplatin in Patients With CCR5+ Metastatic Triple Negative Breast Cancer (mTNBC) [NCT03838367]Phase 1/Phase 248 participants (Anticipated)Interventional2019-04-22Active, not recruiting
A Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Initial Efficacy of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) Injection Combined With Toripalimab and With Standard Chemotherapy in Patients With Advanced Lun [NCT05664971]Phase 1/Phase 2240 participants (Anticipated)Interventional2023-02-09Recruiting
A Multi-Center Randomized Phase 2b Study of Cetuximab (Erbitux) in Combination With Platinum-Based Chemotherapy as First Line Treatment of Patients With Recurrent or Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00828841]Phase 2601 participants (Actual)Interventional2008-12-31Completed
Combination Talazoparib - Carboplatin for Recurrent High-grade Glioma With DNA Damage Repair Deficiency (DDRd) [NCT04740190]Phase 233 participants (Anticipated)Interventional2021-01-01Recruiting
Phase I/II Trial of Neoadjuvant Sunitinib Administered With Weekly Paclitaxel/Carboplatin in Patients With Locally Advanced Triple-Negative Breast Cancer [NCT00887575]Phase 1/Phase 254 participants (Actual)Interventional2009-06-30Completed
A Phase I/II Multi-site Study of Rucaparib and Pembrolizumab Maintenance Therapy in Stage IV Non-Squamous Non-Small Cell Lung Cancer After Initial Therapy With Carboplatin, Pemetrexed, and Pembrolizumab [NCT03559049]Phase 1/Phase 225 participants (Actual)Interventional2018-12-24Active, not recruiting
A Phase II Study of Chidamide or Placebo in Combination With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer [NCT01836679]Phase 2124 participants (Actual)Interventional2013-04-30Completed
A Phase II Trial of a Vascular Endothelial Growth Factor (VEGF) Monoclonal Antibody, AVASTIN, in Combination With Cytotoxic Chemotherapy CARBOPLATIN and PACLITAXEL for Recurrent/Advanced Endometrial Cancer [NCT00879359]Phase 215 participants (Actual)Interventional2007-12-31Completed
Evaluation of the Sensitivity to Different Chemotherapy Regimens in Platinum-Partial Sensitive Recurrent Ovarian Cancer Based on 11 Gene Tests of Homologous Recombination Pathway [NCT04337632]Phase 3338 participants (Anticipated)Interventional2017-08-01Recruiting
Randomized Phase III Trial of Chemotherapy vs. Pembrolizumab Plus Chemotherapy for Relapsed/Refractory Classical Hodgkin Lymphoma [NCT05711628]Phase 30 participants (Actual)Interventional2023-08-10Withdrawn(stopped due to Other - Protocol moved to Withdrawn)
A Phase II Study of Pembrolizumab in Combination With Circulating Tumor DNA Response-Adaptive Pulsed Chemotherapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma: The SINERGY Trial (Squamous Cell Carcinoma of Head and Neck Response-Guided Th [NCT05420948]Phase 230 participants (Anticipated)Interventional2022-10-17Recruiting
Phase II Multi-center Study of Pembrolizumab in Combination With Platinum-based Doublet Chemotherapy in NSCLC (Non-small Cell Lung Cancer) Patients With Targetable Genetic Alterations in Their Tumor Previously Treated With Appropriate Targeted Agents With [NCT03242915]Phase 233 participants (Actual)Interventional2017-10-03Active, not recruiting
A Pilot Study of Response-Driven Adaptive Radiation Therapy for Patients With Locally Advanced Non-Small Cell Lung Cancer [NCT02492867]49 participants (Actual)Interventional2016-01-14Completed
A Randomized Phase III Trial Comparing Conventional-Dose Chemotherapy Using Paclitaxel, Ifosfamide, and Cisplatin (TIP) With High-Dose Chemotherapy Using Mobilizing Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin and Etoposide (TI-CE) as Firs [NCT02375204]Phase 3420 participants (Actual)Interventional2015-08-05Active, not recruiting
Randomized Phase II Study of DCE-MRI-based Dose Escalation for Poor-prognosis and Neck Cancer [NCT02031250]Phase 2106 participants (Actual)Interventional2014-02-28Active, not recruiting
Evaluation of Circulating T Cells and Tumor Infiltrating Lymphocytes With Specificities Against Tumor Associated Antigens During and After Neoadjuvant Chemotherapy and Phased Ipilimumab in Non-Small Cell Lung Cancer [NCT01820754]Phase 224 participants (Actual)Interventional2013-03-31Completed
A Phase I/II, Open Label Study to Assess the Efficacy and Safety of ABTL0812 in Combination With Paclitaxel and Carboplatin in Patients With Advanced Endometrial Cancer or Squamous NSCLC [NCT03366480]Phase 1/Phase 2103 participants (Actual)Interventional2016-12-01Completed
Randomized Open Label Phase II Trial of Neoadjuvant Carboplatin Plus Docetaxel or Carboplatin Plus Paclitaxel Followed by Doxorubicin Plus Cyclophosphamide in Stage I-III Triple-negative Breast Cancer [NCT02413320]Phase 2101 participants (Actual)Interventional2015-07-31Completed
Phase II Clinical Study of AK112, an Anti-PD-1 and VEGF Bispecific Antibody, Alone or in Combination With Chemotherapy for the Neoadjuvant/Adjuvant Treatment of Resectable Non-small Cell Lung Cancer [NCT05247684]Phase 230 participants (Anticipated)Interventional2022-02-20Not yet recruiting
A Phase II Study of Whole Blood Hyperthermia and Ice Chemotherapy in Sarcoma Patients [NCT00002974]Phase 234 participants (Anticipated)Interventional1996-07-31Completed
SPECTRA: SupraPhysiological Androgen to Enhance Chemotherapy TReatment Activity [NCT06039371]Phase 246 participants (Anticipated)Interventional2024-01-01Not yet recruiting
Phase II Trial of Carboplatin, Weekly Paclitaxel and Biweekly Bevacizumab in Patients With Unresectable Stage IV Melanoma [NCT00255762]Phase 247 participants (Actual)Interventional2005-12-31Completed
Randomized Phase II Study of Biweekly Gemcitabine-Paclitaxel, Biweekly Gemcitabine-Carboplatin and Biweekly Gemcitabine-Cisplatin as First-Line Treatment in Metastatic Breast Cancer After Anthracycline Failure [NCT00191854]Phase 2147 participants (Actual)Interventional2005-03-31Completed
"A Phase II Study of Abraxane®, Carboplatin and Bevacizumab in Triple Negative (Demonstrating No Expression for Estrogen, Progesterone, or Her2 Receptors) Metastatic Breast Cancer" [NCT00479674]Phase 241 participants (Actual)Interventional2007-05-31Completed
A Phase II Trial of Response-Adapted Second-Line Therapy for Hodgkin Lymphoma Using Anti-PD-1 Antibody Nivolumab ? ICE Chemotherapy as a Bridge to Autologous Hematopoietic Cell Transplant (NICE Trial) [NCT03016871]Phase 278 participants (Actual)Interventional2017-04-24Active, not recruiting
Neoadjuvant Camrelizumab, Nab-paclitaxel and Carboplatin in Patients With Stage IB-IIIA Non-small Cell Lung Cancer (NANE-LC): A Prospective, Single-arm, Multicenter, Phase II Study [NCT04541251]Phase 240 participants (Anticipated)Interventional2020-08-01Recruiting
A Feasibility Study Of NAB-Paclitaxel In Combination With Carboplatin As First Line Treatment Of Gastrointestinal Neuroendocrine Carcinomas [NCT02215447]Phase 24 participants (Actual)Interventional2015-05-31Active, not recruiting
A Phase II Study of Candonilimab (AK104) Combined With Preoperative Chemotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma (ESCC) [NCT05896787]Phase 245 participants (Anticipated)Interventional2023-08-01Not yet recruiting
A Phase II Trial of Atezolizumab + Carboplatin + Etoposide With Liver-Directed Radiotherapy (RT) in Extensive Stage Small Cell Lung Cancer (ES-SCLC) Patients With Liver Metastases [NCT04923776]Phase 218 participants (Anticipated)Interventional2021-09-20Recruiting
A Phase I/II Trial of Brentuximab Vedotin (BV), Ifosfamide (I), Carboplatin (C), and Etoposide (E) for Patients With Relapsed or Refractory Hodgkin Lymphoma (BV-ICE) [NCT02227199]Phase 1/Phase 245 participants (Actual)Interventional2014-10-10Active, not recruiting
Intracerebral Convection Enhanced Delivery of Carboplatin for Treatment of Recurrent High-grade Gliomas [NCT01644955]Phase 110 participants (Actual)Interventional2012-06-11Completed
A Phase I Dose Escalation Study Evaluating Vintafolide (MK-8109) Chemotherapy Alone or in Combination in Adult Subjects With Advanced Cancers [NCT01688791]Phase 137 participants (Actual)Interventional2012-12-31Terminated
A Phase I Study Combining Ibrutinib With Rituximab, Ifosfamide, Carboplatin, and Etoposide (R-ICE) in Patients With Relapsed or Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [NCT02219737]Phase 126 participants (Actual)Interventional2014-09-12Completed
Neoadjuvant Chemotherapy in Resectable NSCLC Stages IB, IIA, IIB, and IIIA/T3 But Not IIIA/N2 [NCT00273507]Phase 3270 participants Interventional1998-01-31Terminated
An Open -Label, Phase II Trial of Increasing Doses of ABI-007 and Carboplatin in Patients With Advanced Non Small Cell Lung Cancer (NSCLC) [NCT00274443]Phase 2250 participants (Actual)Interventional2005-03-01Completed
UKCCSG Stage IIB/3 (INSS) Neuroblastoma Pilot Study [ENSG VI (Pilot 2B/3)] [NCT00416676]Phase 330 participants (Anticipated)InterventionalActive, not recruiting
Phase II Study of Weekly Carboplatin and Taxotere in Platinum Sensitive Relapsed Ovarian or Tubal or Primary Peritoneal Cancers [NCT00247988]Phase 238 participants Interventional2003-10-31Terminated(stopped due to Regulatory issues(trial temporarily suspended December 28, 2005. Permanently suspended January 19, 2007. Institutional Reveiw Board informed April 18, 2007)
An Open Label Phase I Dose Escalation Trial of Oral BIBF 1120 in Combination With Intravenous Carboplatin and Vinorelbine in Elderly Patients With Advanced Non-Small Cell Lung Cancer - Stage IV [NCT01683682]Phase 18 participants (Actual)Interventional2013-04-30Completed
Phase I Study Of Suberoylanilide Hydroxamic Acid (SAHA) (NSC 701852) in Combination With Paclitaxel /Carboplatin for Advanced and Refractory Solid Malignancies [NCT00287937]Phase 130 participants (Actual)Interventional2005-07-31Completed
An Open-label, Phase II Study of KN046 Evaluating the Efficacy and Safety of KN046 Plus Platinum-based Doublet Chemotherapy as First Line Therapy in Advanced Non-small Cell Lung Cancer Subjects. [NCT04054531]Phase 250 participants (Anticipated)Interventional2019-09-04Recruiting
SIOP Intracranial Germ Cell Tumours Protocol [NCT00293358]Phase 3500 participants (Anticipated)Interventional1997-01-31Completed
A Phase I/II Study of Patients With Newly Diagnosed Primary Central Nervous System Lymphoma Treated With Methotrexate/BBBD, and Adding Rituximab (an Anti CD-20 Antibody) and Carboplatin, to the Treatment Regimen [NCT00293475]Phase 1/Phase 281 participants (Anticipated)Interventional2005-10-14Active, not recruiting
A Phase I/II Trial: Docetaxel, Irinotecan, and Carboplatin in the Treatment of Extensive Stage Small Cell Lung Carcinoma [NCT00264134]Phase 1/Phase 240 participants Interventional2003-06-30Terminated
A Phase III Randomised, Double-Blind, Placebo-Controlled, Multicentre Study of Durvalumab in Combination With Chemotherapy and Bevacizumab, Followed by Maintenance Durvalumab, Bevacizumab and Olaparib in Newly Diagnosed Advanced Ovarian Cancer Patients (D [NCT03737643]Phase 31,407 participants (Actual)Interventional2019-01-04Active, not recruiting
A Randomized Phase III Trial of Vinorelbine Versus Gemcitabine and Carboplatin for Elderly Patients With Advanced Non-Small Cell Lung Cancer [NCT00265694]Phase 30 participants InterventionalRecruiting
Randomized Phase II Trial of Intensive Induction Chemotherapy (CBOP/BEP) and Standard BEP Chemotherapy in Poor Prognosis Male Germ Cell Tumors [NCT00301782]Phase 288 participants (Anticipated)Interventional2005-06-30Completed
Phase II Study of Carboplatin and Vinorelbine i.v. (Day 1) and Orally (Day 8) for Malignant Pleural Mesothelioma [NCT00272558]Phase 240 participants (Anticipated)Interventional2004-09-30Completed
Phase II Study of Irinotecan, Carboplatin, Bevacizumab, and Radiation Therapy in the Treatment of Patients With Limited Stage Small Cell Lung Cancer [NCT00308529]Phase 255 participants Interventional2006-03-31Completed
Phase I/II Lapatinib Plus Carboplatin and Paclitaxel in Stage III or IV Relapsed Ovarian or Stage IV Breast Cancer Patients [NCT00316407]Phase 1/Phase 230 participants (Actual)Interventional2005-08-31Completed
LCCC 0215: Induction Chemotherapy Using Paclitaxel, Carboplatin, CPT-11 With Pegfilgrastim Support Followed by Conformal Radiotherapy and Paclitaxel/Carboplatin/ZD1839 in Locally Advanced Unresectable Stage IIIA/B Non-Small Cell Carcinoma of the Lung [NCT00280787]Phase 224 participants (Actual)Interventional2003-11-30Completed
European Infant Neuroblastoma Study Final Protocol [NCT00417053]Phase 30 participants InterventionalActive, not recruiting
A Phase II Trial of PS-341 in Combination With Paclitaxel and Carboplatin for the Treatment of Metastatic Melanoma [NCT00288041]Phase 236 participants (Anticipated)Interventional2005-10-31Completed
An Adaptive Randomized Neoadjuvant Two Arm Trial in Triple-negative Breast Cancer Comparing a Mono Atezolizumab Window Followed by a Atezolizumab - CTX Therapy With Atezolizumab - CTX Therapy (neoMono) [NCT04770272]Phase 2416 participants (Actual)Interventional2021-03-01Active, not recruiting
Phase II Trial of Carboplatin and Everolimus (RAD001) in Metastatic Castrate Resistant Prostate Cancer (CRPC) Pretreated With Docetaxel Chemotherapy. [NCT01051570]Phase 226 participants (Actual)Interventional2010-02-28Completed
A Phase 1b, Multicenter Study to Determine the Dose, Safety, Efficacy and Pharmacokinetics of TRK-950 When Used in Combinations With Selected Anti-Cancer Treatment Regimens in Patients With Selected Advanced Solid Tumors [NCT03872947]Phase 1169 participants (Anticipated)Interventional2019-04-26Recruiting
A Phase I Multicenter Study of Immunotherapy in Combination With Chemoradiation in Patients With Advanced Solid Tumors (CLOVER) [NCT03509012]Phase 1105 participants (Actual)Interventional2018-05-02Active, not recruiting
A Randomized Phase II Pilot Trial of Carboplatin Compared to Docetaxel for Patients With Metastatic Genetic Breast Cancer [BRCA Trial] [NCT00321633]Phase 2148 participants (Anticipated)Interventional2005-09-30Completed
Multicenter Therapy Optimizing Study for Treatment of Children and Adolescents With Intracranial Medulloblastoma / PNET and Ependymoma [NCT00303810]567 participants (Actual)Interventional2001-01-31Completed
A Phase I/II Dose Escalation Trial of Carboplatin With Amifostine Pretreatment to Augment High Dose Cyclophosphamide With Autologous Peripheral Blood Stem Cell Support for the Treatment of Patients With Epithelial Ovarian Cancer [NCT00003136]Phase 1/Phase 211 participants (Actual)Interventional1996-12-31Completed
Pembrolizumab With Standard Cytotoxic Chemotherapy in Treatment Naive Non-small Cell Lung Cancer Patients With Asymptomatic Brain Metastases [NCT04967417]Phase 250 participants (Anticipated)Interventional2021-10-31Not yet recruiting
A Multicenter Randomized Phase II Study of First Line Treatment With Sequential Administration of Docetaxel, Carboplatin and Herceptin Versus the Administration of Vinorelbine and Herceptin Combination in HER-2 Positive Patients With Metastatic Breast Can [NCT00453635]Phase 288 participants (Actual)Interventional2003-12-31Terminated(stopped due to Due to poor accrual)
A Multicenter, Open Phase Ib Study of the Safety and Efficacy of BEBT-908 Combined With Drugs in the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma [NCT06164327]Phase 175 participants (Anticipated)Interventional2023-12-01Recruiting
A Randomized Phase II Study of Nivolumab Versus Nivolumab and BMS-986016 (Relatlimab) as Maintenance Treatment After First-Line Treatment With Platinum-Gemcitabine-Nivolumab for Patients With Epstein-Barr Virus-Associated Recurrent/Metastatic Nasopharynge [NCT06029270]Phase 2156 participants (Anticipated)Interventional2024-02-16Not yet recruiting
A Phase II, Multicentre, Open-label, Master Protocol to Evaluate the Efficacy and Safety of Datopotamab Deruxtecan (Dato-DXd) as Monotherapy and in Combination With Anticancer Agents in Patients With Advanced/Metastatic Solid Tumours [NCT05489211]Phase 2670 participants (Anticipated)Interventional2022-09-06Recruiting
Phase Ib Study of Dovitinib in Combination With Gemcitabine Plus Cisplatin or Gemcitabine Plus Carboplatin in Patients With Advanced Solid Tumors [NCT01496534]Phase 114 participants (Actual)Interventional2012-01-31Terminated(stopped due to toxicity of combination of medications)
A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Metmab Vs. Placebo in Combination With Either Bevacizumab + Platinum + Paclitaxel or Pemetrexed + Platinum in Patients With Untreated Stage I [NCT01496742]Phase 2259 participants (Actual)Interventional2012-04-30Completed
An Open-Label, One-Arm, One-Sequence Crossover Drug-Drug Interaction Study in Advanced Solid Tumor Subjects Subjects to Evaluate the Potential Effect of Custirsen (OGX-011) on the Pharmacokinetics of Paclitaxel [NCT01497470]Phase 136 participants (Actual)Interventional2012-04-30Completed
Randomized Phase II Trial of Individualized Adaptive Radiotherapy Using During-Treatment FDG-PET/CT and Modern Technology in Locally Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT01507428]Phase 2138 participants (Actual)Interventional2012-02-22Active, not recruiting
A Phase 1 Study of Veliparib (ABT-888) in Combination With Carboplatin/Paclitaxel in Japanese Subjects With Solid Tumors [NCT01617928]Phase 112 participants (Actual)Interventional2012-05-31Completed
Phase I/II BNC105P Combination Study in Partially Platinum Sensitive Ovarian Cancer Patients in First or Second Relapse [NCT01624493]Phase 1/Phase 20 participants (Actual)Interventional2012-10-31Withdrawn(stopped due to Phase I was conducted Australia. Phase II not conducted and no US pts enrolled.)
An Intergroup Pilot Study of Concurrent Carboplatin, Vincristine and Radiotherapy Followed by Adjuvant Chemotherapy in Patients With Newly Diagnosed High-Risk Central Nervous System Embryonal Tumors [NCT00003203]Phase 2168 participants (Actual)Interventional1998-03-31Completed
A Phase Ib Study of the Safety and Pharmacology of Atezolizumab (Anti-PD-L1 Antibody) Administered With Bevacizumab and/or Chemotherapy in Patients With Advanced Solid Tumors [NCT01633970]Phase 1240 participants (Actual)Interventional2012-07-11Completed
Phase I Study of the Combination of Vemurafenib With Carboplatin and Paclitaxel in Patients With Advanced Malignancy [NCT01636622]Phase 121 participants (Actual)Interventional2012-07-09Completed
Chemo-Immunotherapy: Observational Trial of Carboplatin-pegylated Liposomal Doxorubicin (PLD) or Doxorubicin Combination Chemotherapy With Tocilizumab, a Humanized Monoclonal Antibody Against the Human Interleukin-6 (IL-6) Receptor, and Pegylated Interfer [NCT01637532]Phase 1/Phase 221 participants (Actual)Interventional2011-02-28Completed
Phase Ib With Expansion of Patients at the MTD Study of Olaparib Plus Weekly (Metronomic) Carboplatin and Paclitaxel in Relapsed Ovarian Cancer Patients [NCT01650376]Phase 1/Phase 252 participants (Anticipated)Interventional2012-08-31Active, not recruiting
A Phase 1 Study of Carboplatin and Gemcitabine Chemotherapy and Stereotactic Body Radiosurgery for the Palliative Treatment of Persistent or Recurrent Gynecologic Cancer [NCT01652794]Phase 112 participants (Actual)Interventional2012-05-31Completed
Randomized Phase II Trial Using Concomitant Chemoradiation Plus Induction or Consolidation Chemotherapy for Unresectable Stage III Non-small Cell Lung Cancer Patients [NCT01652820]Phase 2140 participants (Actual)Interventional2001-10-31Completed
A Phase Ib Ascending Multi-arm, Dose Escalation Study of BMS-906024 Combined With Several Chemotherapy Regimens in Subjects With Advanced or Metastatic Tumors [NCT01653470]Phase 1141 participants (Actual)Interventional2012-10-12Completed
An International Phase III Randomised Trial of Dose Fractionated Chemotherapy Compared to Standard Three Weekly Chemotherapy, Following Immediate Primary Surgery or as Part of Delayed Primary Surgery, for Women With Newly Diagnosed Epithelial Ovarian, Fal [NCT01654146]Phase 31,485 participants (Anticipated)Interventional2011-06-30Recruiting
Phase I Dose Escalation Study of Carboplatin, Pemetrexed and Exemestane in Post-menopausal Women With Metastatic Non-squamous NSCLC [NCT01664754]Phase 18 participants (Actual)Interventional2012-09-07Completed
A Phase II Study of Ipilimumab in Combination With Carboplatin and Paclitaxel in Patients With Unresectable Stage III or Stage IV Melanoma [NCT01676649]Phase 230 participants (Actual)Interventional2012-11-30Active, not recruiting
Patient-reported Outcome-based Surveillance System Evaluating Safety and Efficacy of Preoperative Immunochemotherapy +/- Chemoradiation in Patients With Esophageal Squamous Cell Carcinoma - A Prospective, Explorative, Phase II Study [NCT05596890]Phase 250 participants (Anticipated)Interventional2022-11-30Recruiting
Neoadjuvant Nab-paclitaxel in Triple-negative or HER2-positive Breast Cancer [NCT03907800]Phase 2100 participants (Anticipated)Interventional2019-04-01Recruiting
A Multicentre Randomised Phase II Trial of Neo-adjuvant Chemotherapy Followed by Surgery vs. Neo-adjuvant Chemotherapy and Subsequent Chemoradiotherapy Followed by Surgery vs. Neo-adjuvant Chemoradiotherapy Followed by Surgery in Resectable Gastric Cancer [NCT02931890]Phase 2207 participants (Anticipated)Interventional2017-12-21Recruiting
A Phase IA/IB Trial of PTX-200 and Carboplatin in Patients With Platinum-Resistant Recurrent Ovarian Cancer [NCT01690468]Phase 1/Phase 215 participants (Actual)Interventional2014-09-30Terminated(stopped due to Enrollment stopped prior to Phase 1b, change in strategic focus)
Phase II Trial of Neoadjuvant Therapy With Paclitaxel and Carboplatin in Operable Locally Advanced Head and Neck Cancer Patients (NEOS) [NCT05294900]Phase 279 participants (Anticipated)Interventional2022-05-31Not yet recruiting
A Phase 2 Multi-Center Randomized Trial to Assess Early Intervention With Adjuvant Nivolumab in Non-Small Cell Lung Cancer Participants With ctDNA-detected Minimal Residual Disease After Surgical Resection [NCT03770299]Phase 20 participants (Actual)Interventional2021-01-15Withdrawn(stopped due to Business objectives have changed)
Feasibility Study of Neo-adjuvant Treatment With Carboplatin, Paclitaxel and Pembrolizumab in Primary Stage IV Serous Ovarian Cancer [NCT03126812]Phase 1/Phase 230 participants (Anticipated)Interventional2017-11-01Recruiting
Phase 2 Study of the Safety, Efficacy, and Pharmacokinetics of G1T28 in Patients With Metastatic Triple Negative Breast Cancer Receiving Gemcitabine and Carboplatin Chemotherapy [NCT02978716]Phase 2102 participants (Actual)Interventional2017-02-02Terminated(stopped due to Primary Analysis and survival follow up completed per protocol. Not stopped due to safety concerns)
A Phase III, Open-Label, Multicenter, Randomized Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel or Atezolizumab in Combination With Carboplatin+Nab-Paclitaxel Versus Car [NCT02367794]Phase 31,021 participants (Actual)Interventional2015-06-11Completed
Phase I Dose Escalation Study of Everolimus, Pemetrexed, Carboplatin, and Bevacizumab in Stage IV Non-Squamous Non-Small Cell Lung Cancer [NCT01700400]Phase 113 participants (Actual)Interventional2012-09-30Completed
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Fosbretabulin Tromethamine (CA4P) in Combination With Paclitaxel and Carboplatin in Anaplastic Thyroid Carcinoma (FACT2) [NCT01701349]Phase 30 participants (Actual)Interventional2015-03-31Withdrawn(stopped due to Expected inability to recruit study participants in a reasonable amount of time.)
A MULTICENTER, OPEN-LABEL PHASE IB STUDY OF RO5083945 IN COMBINATION WITH CISPLATIN AND GEMCITABINE OR CARBOPLATIN AND PACLITAXEL IN PATIENTS WITH ADVANCED OR RECURRENT NON SMALL CELL LUNG CANCER OF SQUAMOUS HISTOLOGY WHO HAVE NOT RECEIVED PRIOR CHEMOTHER [NCT01702714]Phase 10 participants (Actual)Interventional2014-07-31Withdrawn(stopped due to Project Team decision)
Phase 1 / 2 Trial of Blood-brain Barrier Opening With an Implantable Ultrasound Device SonoCloud-9 and Treatment With Albumin-bound Paclitaxel and Carboplatin in Patients With Recurrent Glioblastoma [NCT04528680]Phase 1/Phase 257 participants (Anticipated)Interventional2020-10-29Recruiting
High Risk Neuroblastoma Study 1 of SIOP-Europe (SIOPEN) [NCT01704716]Phase 33,300 participants (Anticipated)Interventional2002-02-28Recruiting
Phase II Trial of Neoadjuvant Platinum-based Chemotherapy for Patients With Resectable , Non-small Cell Lung Cancer With Switch to Chemotherapy Alternative in Nonresponders (NEOSCAN) [NCT01443078]Phase 242 participants (Actual)Interventional2011-10-31Completed
An Alternative Radiation Fractionation Strategy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT01711697]Phase 116 participants (Actual)Interventional2012-09-04Active, not recruiting
Multicenter, Randomized, Non-comparative, Phase II Trial on the Efficacy and Safety of the Combination of Bevacizumab and Trabectedin With or Without Carboplatin in Adult Women With Platinum Partially Sensitive Recurring Ovarian Cancer. [NCT01735071]Phase 271 participants (Actual)Interventional2013-07-31Completed
A Randomized, Open-Label, Phase II Study Assessing the Efficacy and the Safety of Bevacizumab in Neoadjuvant Therapy in Patients With FIGO Stage IIIC/IV Ovarian, Tubal or Peritoneal Adenocarcinoma, Initially Unresectable [NCT01739218]Phase 299 participants (Actual)Interventional2013-02-01Completed
Molecular Profiling-Based Assignment of Cancer Therapy for Patients With Advanced Solid Tumors [NCT01827384]Phase 2208 participants (Actual)Interventional2014-01-07Completed
A Randomised Phase II/III Study of Concurrent Cisplatin-Radiotherapy With or Without Induction Chemotherapy Using Gemcitabine, Carboplatin and Paclitaxel in Locally Advanced Nasopharyngeal Cancer [NCT00997906]Phase 2/Phase 3172 participants (Actual)Interventional2009-09-15Active, not recruiting
A Single-arm, Phase II Clinical Trial to Treat Muscle-invasive Bladder Cancer With Induction Chemotherapy Plus Anti-PD-1 Therapy Followed by Radiotherapy Plus Concurrent Anti-PD-1 Therapy [NCT05975307]Phase 264 participants (Anticipated)Interventional2023-12-01Recruiting
S2210 A Phase II Study of Neoadjuvant Carboplatin for Localized, High Risk Prostate Cancer With Germline BRCA1/2 Mutations [NCT05806515]Phase 244 participants (Anticipated)Interventional2024-03-01Recruiting
A Phase 2 Trial of Combination Therapies With Adagrasib in Patients With Advanced Non-Small Cell Lung Cancer With KRAS G12C Mutation [NCT05609578]Phase 290 participants (Anticipated)Interventional2022-07-29Recruiting
SiCARIO (Split Course Adaptive Radioimmunotherapy) for the Treatment of Oligometastatic Non-Small Cell Lung Cancer (NSCLC) Using Biologically-Adaptive Radiotherapy - A Phase I/II Study [NCT05501665]Phase 1/Phase 225 participants (Anticipated)Interventional2023-05-09Recruiting
A Randomized, Phase 2 Study of Pembrolizumab And Chemotherapy With or Without MK-4830 as Neoadjuvant Treatment for High-Grade Serous Ovarian Cancer [NCT05446870]Phase 2160 participants (Actual)Interventional2022-07-25Active, not recruiting
Randomized Phase II/III Trial of First Line Platinum/Etoposide With or Without Atezolizumab (NSC#783608) in Patients With Poorly Differentiated Extrapulmonary Small Cell Neuroendocrine Carcinomas (NEC) [NCT05058651]Phase 2/Phase 3189 participants (Anticipated)Interventional2022-06-28Recruiting
A Randomized Phase II/III Trial of Modern Immunotherapy Based Systemic Therapy With or Without SBRT for PD-L1-Negative, Advanced Non-Small Cell Lung Cancer [NCT04929041]Phase 2/Phase 3427 participants (Anticipated)Interventional2022-10-07Recruiting
A Phase 2 Study to Evaluate the Efficacy and Safety of Pembrolizumab Plus Investigational Agents in Combination With Etoposide and Cisplatin or Carboplatin for the First-Line Treatment of Participants With Extensive-Stage Small Cell Lung Cancer (KEYNOTE-B [NCT04924101]Phase 2120 participants (Anticipated)Interventional2021-07-15Active, not recruiting
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Platinum Plus Pemetrexed Chemotherapy Plus Osimertinib Versus Platinum Plus Pemetrexed Chemotherapy Plus Placebo in Patients With EGFRm, Locally Advanced or Metastatic NSCLC Who Have Progr [NCT04765059]Phase 380 participants (Anticipated)Interventional2021-09-12Recruiting
A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With A [NCT04644068]Phase 1/Phase 2804 participants (Anticipated)Interventional2020-11-12Recruiting
A Phase 3 Study of Pembrolizumab (MK-3475) in Combination With Concurrent Chemoradiation Therapy Followed by Pembrolizumab With or Without Olaparib vs Concurrent Chemoradiation Therapy Followed by Durvalumab in Participants With Unresectable, Locally Adva [NCT04380636]Phase 3870 participants (Anticipated)Interventional2020-07-06Active, not recruiting
Phase 1/2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, as a Single Agent and Combined With Chemotherapy, in Patients With Refractory Hematologic Malignancies or Solid Tumors [NCT03678883]Phase 2350 participants (Anticipated)Interventional2019-01-04Recruiting
Phase II Randomized Trial of Neo-Adjuvant Chemotherapy Followed by Surgery and Post-Operative Radiation Versus Surgery and Post-Operative Radiation for Organ Preservation of T3 and T4a Nasal and Paranasal Sinus Squamous Cell Carcinoma (NPNSCC) [NCT03493425]Phase 282 participants (Anticipated)Interventional2019-03-12Recruiting
A Phase III Trial of Carboplatin as Adjuvant Chemotherapy Versus Observation in Triple Negative Breast Cancer With Pathologic Residual Cancer After Neoadjuvant Chemotherapy: POST-Neo Adjuvant Study [NCT01752686]Phase 3587 participants (Anticipated)Interventional2013-03-31Not yet recruiting
Randomized, Double-blind, Placebo-controlled, Multi-center Study of Camrelizumab Combined With SRT/WBRT and Chemotherapy in Patients of NSCLC With Brain Metastases of Driven Gene-negative and Not Received Systemic Chemotherapy [NCT04768075]Phase 3200 participants (Anticipated)Interventional2021-03-05Not yet recruiting
A Randomized Phase II Trial of Carboplatin-Paclitaxel Compared to Carboplatin-Paclitaxel-Bevacizumab in Advanced (Stage III-IV) or Recurrent Endometrial Cancer [NCT01770171]Phase 2108 participants (Anticipated)Interventional2012-04-30Recruiting
The Clinical Study of Personalized Therapy for Non-small Cell Lung Cancer Based on ERCC1/RRM1/TS Expression [NCT01781988]Phase 2128 participants (Actual)Interventional2009-06-30Completed
DARTBOARD: A Prospective Randomized Phase II Study of Daily Adaptive Radiotherapy to Better Organ-at-Risk Doses in Head and Neck Cancer [NCT04883281]Phase 250 participants (Actual)Interventional2022-02-23Active, not recruiting
A Phase II/III Clinical Trial to Evaluate the Efficacy and Safety of PM8002(Anti-PD-L1/VEGF) in Combination With Chemotherapy in Patients With EGFR-mutant Advanced Non-squamous NSCLC Who Have Failed to EGFR-TKI Treatment [NCT05756972]Phase 2/Phase 3374 participants (Anticipated)Interventional2023-06-26Recruiting
A Prospective Single Arm Non-inferiority Trial of Major Radiation Dose De-Escalation Concurrent With Chemotherapy for Human Papilloma Virus Associated Oropharyngeal Carcinoma (Major De-escalation to 30Gy for Select Human Papillomavirus Associated Orophary [NCT03323463]Phase 2316 participants (Anticipated)Interventional2017-10-16Active, not recruiting
Observational Studies to Explore the Relation Between Angiogenic Markers and the Treatment Response With Carboplatin, Paclitaxel and Bevacizumab in First Line of Advanced Non-small-cell Lung Cancer With Non- Squamous Histology [NCT01814163]200 participants (Actual)Observational2011-02-28Completed
Multi-Center, Randomized, Double-Blind, Phase III Efficacy Study Comparing Phenoxodiol in Combination With Carboplatin Versus Carboplatin With Placebo in Patients With Platinum-Resistant or Platinum-Refractory Late-Stage Epithelial Ovarian, Fallopian or P [NCT00382811]Phase 3142 participants (Actual)Interventional2006-10-31Completed
International, Randomized, Open-Label, Phase 3 Trial of Paclitaxel/Carboplatin Plus PF-3512676 Versus Paclitaxel/Carboplatin Alone as First-Line Treatment of Patients With Advanced Non-Small Cell Lung Cancer [NCT00254891]Phase 3828 participants (Actual)Interventional2005-11-30Terminated(stopped due to See Termination Reason in Detailed Description)
A Dose-finding Phase Ib Study Followed by a Randomized, Double-blind Phase II Study of Carboplatin and Paclitaxel With or Without Buparlisib in Patients With Previously Untreated Metastatic Non-small Cell Lung Cancer (NSCLC) of Squamous Histology [NCT01820325]Phase 16 participants (Actual)Interventional2013-09-09Terminated(stopped due to Due to DLTs/AEs safety profile considered challenging.)
Phase 1b/2a Safety and Pharmacokinetic Study of G1T28 in Patients With Extensive Stage Small Cell Lung Cancer (SCLC) Receiving Etoposide and Carboplatin [NCT02499770]Phase 1/Phase 2122 participants (Actual)Interventional2015-06-26Completed
Multicenter Randomized Phase 2 Trial of Gemcitabine - Platinum With or Without Trastuzumab in Advanced or Metastatic Urothelial Carcinoma With HER2 Overexpression [NCT01828736]Phase 261 participants (Actual)Interventional2004-02-09Completed
A Prospective Randomized Phase III Trial of Carboplatin/Gemcitabine/Bevacizumab vs. Carboplatin/Pegylated Liposomal Doxorubicin/Bevacizumab in Patients With Platinum-sensitive Recurrent Ovarian Cancer [NCT01837251]Phase 3682 participants (Actual)Interventional2013-05-31Completed
A Randomised Phase II Study of Two Pre-operative Chemoradiotherapy Regimens (Oxaliplatin and Capecitabine Followed by Radiotherapy With Either Oxaliplatin and Capecitabine or Paclitaxel and Carboplatin) for Resectable Oesophageal Cancer [NCT01843829]Phase 285 participants (Anticipated)Interventional2013-10-31Recruiting
A Phase I/II Trial of Bendamustine/Treanda®, Rituximab, Etoposide, and Carboplatin for Patients With Relapsed or Refractory Lymphoid Malignancies and Select Untreated Lymphomas (TREC) [NCT01165112]Phase 1/Phase 248 participants (Actual)Interventional2010-09-30Completed
WCC# 59: Pilot Study of Hyperthermic Intraperitoneal Chemotherapy Utilizing Carboplatin in First Recurrence [NCT01144442]10 participants (Actual)Interventional2010-07-27Terminated(stopped due to PI Request)
A Phase 1b Study of Talimogene Laherparepvec (T-VEC) in Combination With Chemotherapy or Endocrine Therapy in Patients With Metastatic, Unresectable, or Locoregionally Recurrent HER2-negative Breast Cancer [NCT03554044]Phase 120 participants (Actual)Interventional2020-02-05Active, not recruiting
A Multicentre, Open-label, Randomised Trial of Neoadjuvant Pegylated Liposomal Doxorubicin Plus Cyclophosphamide Sequential Docetaxel Plus Trastuzumab and Pertuzumab Versus Docetaxel Plus Carboplatin Combined With Trastuzumab and Pertuzumab in HER-2 Posit [NCT05159193]Phase 3372 participants (Anticipated)Interventional2021-12-20Recruiting
Correlation Between Early Myocardial Injury and Intestinal Flora Changes Associated With Oncology Drug Therapy and the Preventive and Curative Effects of Probiotics [NCT05730777]Phase 4200 participants (Anticipated)Interventional2023-02-15Not yet recruiting
International Multicenter Randomized Double Blind Phase III Trial Comparing Safety and Efficacy of BCD-021 (CJSC BIOCAD, Russia) and Paclitaxel + Carboplatin to Avastin® (F. Hoffmann-La Roche Ltd, Switzerland) and Paclitaxel + Carboplatin in Inoperable or [NCT01763645]Phase 3138 participants (Actual)Interventional2012-10-31Completed
Intercalating and Maintenance Use of Iressa vs. Chemotherapy in Selected Advanced NSCLC: a Randomised Study [NCT01404260]Phase 3219 participants (Actual)Interventional2011-06-30Completed
A Randomized, Double-Blind, Placebo-Controlled Study of Chemotherapy Plus Cetuximab in Combination With VTX 2337 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT01836029]Phase 2195 participants (Actual)Interventional2013-10-14Completed
A Single-arm, Open-lable, Multicenter, Phase II Clinical Study of LP002 in Combination With Chemotherapy for Patients With Extensive Stage Small Cell Lung Cancer [NCT04740021]Phase 246 participants (Anticipated)Interventional2020-12-02Recruiting
A Multicentre, Randomized, Open-Label, Phase III Clinical Trial Of Gemcitabine And Carboplatin Followed By Epstein-Barr Virus-Specific Autologous Cytotoxic T Lymphocytes Versus Gemcitabine And Carboplatin As First Line Treatment For Advanced Nasopharyngea [NCT02578641]Phase 3330 participants (Actual)Interventional2014-07-31Completed
RBD-HPV: Risk-Based De-Intensification for HPV+ HNSCC [NCT04849377]Phase 20 participants (Actual)Interventional2022-06-14Withdrawn(stopped due to lack of eligible participants due to change in study criterias)
Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）：A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial [NCT04459611]Phase 260 participants (Actual)Interventional2020-07-01Active, not recruiting
A Phase II Study of Concurrent Chemoradiation Plus Durvalumab (MEDI4736) Followed by Surgery Followed by Adjuvant Durvalumab (MEDI4736) in Medically Operable Patients With Surgically Resectable Stage III (N2) Non-Small Cell Lung Cancer [NCT03871153]Phase 27 participants (Actual)Interventional2019-08-02Terminated(stopped due to Investigator decided to halt study due to low accrual.)
A Phase II Randomized, Open-Labelled, Multicenter Study of Safety & Efficacy of Combination Brigatinib and Carboplatin-Pemetrexed Therapy or Brigatinib Monotherapy as First-Line Treatment in Advanced ALK-Positive Non-Small Cell Lung Cancer [NCT05200481]Phase 2110 participants (Anticipated)Interventional2022-05-18Recruiting
Assessment of Carboplatin Clearance Predictors: A PK Study on NCI-Sponsored Clinical Trials or Standard of Care Treatments Using Carboplatin [NCT03997370]Phase 1350 participants (Anticipated)Interventional2020-01-15Recruiting
A Multi-Center Open Label Single Arm Phase II Trial Evaluating the Efficacy of Palbociclib in Combination With Carboplatin for the Treatment of Unresectable Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma [NCT03194373]Phase 221 participants (Actual)Interventional2017-10-12Completed
An Open-label, Multicenter Study to Evaluate the Efficacy and Safety of HLX07 (Recombinant Humanized Anti-EGFR Monoclonal Antibody Injection) in Advanced nsqNSCLC Patients With High EGFR Expression [NCT05215925]Phase 260 participants (Anticipated)Interventional2023-02-01Not yet recruiting
A Prospective, Single Center, Single Arm, Phase II Clinical Trial of Pyrotinib Combined With Pemetrexed Plus Carboplatin in the First-line Treatment of Patients With HER2 Mutant or Amplified Recurrent / Metastatic Non-small Cell Lung Cancer [NCT04706949]Phase 226 participants (Anticipated)Interventional2020-12-07Recruiting
A Randomized, Multicenter, Multinational, Double-Blind Study to Assess the Efficacy and Safety of MB02 (Bevacizumab Biosimilar Drug) Versus Avastin® in Combination With Carboplatin and Paclitaxel for the Treatment of Subjects With Stage IIIB/IV Non-squamo [NCT03296163]Phase 3627 participants (Actual)Interventional2018-02-06Completed
A Phase I, Open Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Selumetinib (AZD6244; ARRY-142886) in Combination With First Line Chemotherapy Regimens in Patients With Non-Small Cell Lung Cancer ( [NCT01809210]Phase 155 participants (Actual)Interventional2013-04-04Completed
The Use of Glutathione (GSH) for Prevention of Paclitaxel/Carboplatin (TAXOL/CBDCA) Induced Peripheral Neuropathy: A Phase III Randomized, Double-Blind Placebo Controlled Study [NCT02311907]Phase 3195 participants (Actual)Interventional2009-12-31Completed
A Pilot Study of FOLFIRINOX in Combination With Neoadjuvant Radiation for Gastric and GE Junction Cancers [NCT03279237]Phase 125 participants (Actual)Interventional2017-10-24Active, not recruiting
Atezolizumab/Carboplatin/Nab-Paclitaxel vs. Pembrolizumab/Platinum/Pemetrexed in Metastatic TTF-1 Negative Lung Adenocarcinoma [NCT05689671]Phase 4136 participants (Anticipated)Interventional2023-12-06Recruiting
A Phase II Trial of Taxotere, Carboplatin and Herceptin in Locally Advanced or Inflammatory Breast Cancer [NCT00118053]Phase 25 participants (Actual)Interventional2005-04-30Terminated(stopped due to slow accrual)
A Phase 1b/2, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Sotorasib Monotherapy and in Combination With Other Anti-cancer Therapies in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) [NCT04185883]Phase 1/Phase 21,143 participants (Anticipated)Interventional2019-12-17Recruiting
A Randomized Double Blind Phase II Trial of Restorative Microbiota Therapy (RMT) in Combination With Durvalumab (MEDI4736) and Chemotherapy in Untreated Patients With Advanced or Metastatic Adenocarcinoma Non-Small Cell Lung Cancer [NCT04105270]Phase 282 participants (Anticipated)Interventional2022-11-30Recruiting
A Randomized Phase 2 Study of LY2510924 and Carboplatin/Etoposide Versus Carboplatin/Etoposide in Extensive-Stage Small Cell Lung Carcinoma [NCT01439568]Phase 290 participants (Actual)Interventional2011-09-30Completed
Phase II Study to Evaluate the Role of Postoperative Radiotherapy for Low Risk of Locoregional Recurrence Patients With Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer [NCT02977169]Phase 2300 participants (Anticipated)Interventional2016-11-30Recruiting
A TRIAL OF INTENSIVE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL RECONSTITUTION FOR PATIENTS BETWEEN SIX AND SIXTY YEARS OF AGE, WITH NON-PROGRESSIVE GLIOBLASTOMA MULTIFORME OR DIFFUSE INTRINSIC BRAINSTEM TUMORS, FOLLOWING INITIAL LOCAL-FIELD IRRADIATION [NCT00002619]Phase 260 participants (Anticipated)Interventional1994-09-30Completed
HIGH DOSE CHEMORADIOTHERAPY WITH PERIPHERAL BLOOD PROGENITOR CELL TRANSPLANTATION FOR PATIENTS WITH PRIMARY REFRACTORY, RELAPSED AND POOR PROGNOSIS NON-HODGKIN'S LYMPHOMA [NCT00002697]Phase 20 participants Interventional1995-09-30Completed
A Randomized, Double-Blind, Phase 3 Study of Pemetrexed + Platinum Chemotherapy With or Without Pembrolizumab (MK-3475) in TKI-resistant EGFR-mutated Tumors in Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) Participants (KEYNOTE-789) [NCT03515837]Phase 3492 participants (Actual)Interventional2018-06-29Completed
A Randomized Phase II Study of Carboplatin and Pemetrexed w/ or w/o Selpercatinib in Participants With Non-Squamous RET Fusion-Positive Stage IV Non-Small Cell Lung Cancer and Progression of Disease on Prior RET Directed Therapy (Lung-MAP Sub-Study) [NCT05364645]Phase 274 participants (Anticipated)Interventional2022-07-25Recruiting
Randomised, Multicenter Phase II Study in Patients With Metastatic Breast Cancer With Vinorelbine Plus Carboplatin Versus Gemcitabine Plus Carboplatin [NCT04143906]Phase 2200 participants (Anticipated)Interventional2019-10-25Not yet recruiting
Phase III Postneoadjuvant Study Evaluating Sacituzumab Govitecan, an Antibody Drug Conjugate in Primary HER2-negative Breast Cancer Patients With High Relapse Risk After Standard Neoadjuvant Treatment - SASCIA [NCT04595565]Phase 31,332 participants (Anticipated)Interventional2020-10-28Recruiting
A Phase II Study Investigating CHFR Methylation Status As A Biomarker For Taxane Sensitivity Using Modified Docetaxel, Cisplatin and 5 Fluorouracil In Patients With Metastatic Esophageal, Gastroesophageal And Gastric Cancer. [NCT01715233]Phase 227 participants (Actual)Interventional2012-12-31Completed
Multimodality Therapy With Induction Carboplatin/Nab-Paclitaxel/Durvalumab Followed by Surgical Resection and Risk-adapted Adjuvant Therapy for the Treatment of Locally-Advanced and Surgically Resectable Squamous Cell Carcinoma of the Head and Neck [NCT03174275]Phase 239 participants (Actual)Interventional2017-12-19Active, not recruiting
A Co-clinical Trial in Triple Negative Breast Cancer Patients With Genoproteomic Discovery [NCT02124902]Phase 2148 participants (Actual)Interventional2014-07-07Terminated(stopped due to Insufficient funding/staff)
Pilot and Translational Study of Dasatinib (NSC#732517) Paclitaxel and Carboplatin in Women With Advanced Stage and Recurrent Endometrial Cancer [NCT01440998]Phase 118 participants (Actual)Interventional2011-09-20Completed
Randomized Phase 2 Trial of Gemcitabine + Carboplatin + Nivolumab Versus Gemcitabine + Oxaliplatin + Nivolumab in Cisplatin-ineligible Patients With Metastatic Urothelial Cancer [NCT03451331]Phase 248 participants (Actual)Interventional2018-05-10Active, not recruiting
PD-1 Monoclonal Antibody Camrelizumab Combined With Albumin Paclitaxel and Platinum for Neoadjuvant Treatment of Adcanced Esophageal Squamous Cell Carcinoma (ESCC): A Single-center, Single-arm Phase II Clinical Study [NCT04767295]Phase 228 participants (Anticipated)Interventional2021-03-01Recruiting
A Phase I Trial of Enzastaurin (LY317615) in Combination With Carboplatin in Adults With Recurrent Gliomas [NCT01445119]Phase 158 participants (Actual)Interventional2007-01-31Completed
A Phase Ib Multicenter, Open-label Study to Evaluate the Safety and Tolerability of Trastuzumab Deruxtecan (T-DXd) and Immunotherapy Agents With and Without Chemotherapy Agents in First-line Treatment of Patients With Advanced or Metastatic Non-squamous N [NCT04686305]Phase 1168 participants (Anticipated)Interventional2021-03-09Recruiting
A Phase I Study With an Expansion Cohort of the PARP Inhibitor AZD2281 (KU-0059436) Combined With Carboplatin in Breast and Ovarian Cancer in BRCA1/2 Mutation Carriers (Familial Breast and Ovarian Cancer) and Sporadic Triple Negative Breast Cancer and Ova [NCT01445418]Phase 1103 participants (Actual)Interventional2008-05-12Completed
Neoadjuvant Anti-PD-1 Drug Nivolumab Combined With Chemotherapy in the Treatment of Primary Tracheal Squamous Cell Carcinoma [NCT05964101]Phase 225 participants (Anticipated)Interventional2023-08-01Not yet recruiting
A Non-randomized Control Study Comparing Weekly Versus Every Three Weeks of Carboplatin Plus Paclitaxel in Patients With Advanced Epithelial Ovarian Cancer [NCT05963334]Phase 1/Phase 249 participants (Actual)Interventional2015-01-01Completed
Phase II Trial of Platinum-Etoposide Chemotherapy and Durvalumab (MEDI4736) With Sub-Ablative SBRT in Patients With Newly Diagnosed Stage IV Small Cell Lung Cancer [NCT04951115]Phase 242 participants (Anticipated)Interventional2021-07-12Active, not recruiting
A Multicentre, Open-label, Three-arm Randomised Phase II Trial Assessing the Safety and Efficacy of the HSP90 Inhibitor Ganetespib in Combination With Carboplatin Followed by Maintenance Treatment With Niraparib Versus Ganetespib Plus Carboplatin Followed [NCT03783949]Phase 2122 participants (Actual)Interventional2018-11-30Completed
A Randomised, Double-blind, Parallel Group, Equivalence, Multicentre Phase III Trial to Compare the Efficacy, Safety, Pharmacokinetics and Immunogenicity of HD204 to Avastin® in Patients With Metastatic or Recurrent Non-squamous Non-small Cell Lung Cancer [NCT03390686]Phase 3650 participants (Actual)Interventional2019-11-15Active, not recruiting
An International Clinical Program for the Diagnosis and Treatment of Children, Adolescents and Young Adults With Ependymoma [NCT02265770]Phase 2/Phase 3536 participants (Anticipated)Interventional2015-06-02Recruiting
Multimodality Risk Adapted Therapy Including Carboplatin/Paclitaxel/Lapatinib as Induction for Squamous Cell Carcinoma of the Head and Neck Amenable to Transoral Surgical Approaches [NCT01612351]Phase 240 participants (Actual)Interventional2012-06-30Active, not recruiting
A Randomized Phase II/III Trial of Intravenous (IV) Paclitaxel Weekly Plus IV Carboplatin Once Every 3 Weeks Versus IV Paclitaxel Weekly Plus Intraperitoneal (IP) Carboplatin Once Every 3 Weeks in Women With Epithelial Ovarian, Fallopian Tube or Primary P [NCT01506856]Phase 2/Phase 3655 participants (Actual)Interventional2010-05-31Completed
A Phase I Study of Avelumab Plus Utomilumab-Based Combination Therapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma and Mantle Cell Lymphoma [NCT03440567]Phase 116 participants (Anticipated)Interventional2018-04-02Active, not recruiting
Phase I/Ib Study of Carfilzomib Plus Rituximab Plus Ifosfamide Plus Carboplatin Plus Etoposide (C-R-ICE) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [NCT01959698]Phase 129 participants (Actual)Interventional2014-04-17Active, not recruiting
I-SPY Trial (Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis 2) [NCT01042379]Phase 25,000 participants (Anticipated)Interventional2010-03-01Recruiting
A Phase II Trial of Durvalumab and Ablative Radiation in Extensive-Stage Small Cell Lung Cancer (DARES) [NCT05068232]Phase 249 participants (Anticipated)Interventional2022-08-19Recruiting
Comparison of Concurrent Chemoradiation Therapy With Weekly Cisplatin and Concurrent Chemoradiation Therapy With Weekly Carboplatin in Locally Advanced Cervical Cancer: Phase III Multicenter Prospective Randomized Controlled Trial [NCT01461772]Phase 321 participants (Actual)Interventional2009-12-31Terminated(stopped due to Because of very slow rate of enrollement)
Phase II Trial of Docetaxel and Carboplatin as Neoadjuvant Chemotherapy in Patients With Advanced Ovarian Cancer [NCT01462149]Phase 243 participants (Actual)Interventional2011-10-31Completed
A Phase 3, Randomized, Double-Blind Study of MK-7684A in Combination With Etoposide and Platinum Followed by MK-7684A vs Atezolizumab in Combination With Etoposide and Platinum Followed by Atezolizumab for the First-Line Treatment of Participants With Ext [NCT05224141]Phase 3450 participants (Anticipated)Interventional2022-03-24Active, not recruiting
REPLATINUM: A Phase 3, Controlled, Open-label, Global Randomized Study of RRx-001 Administered Sequentially With a Platinum Doublet or a Platinum Doublet in Third-Line or Beyond Small Cell Lung Cancer [NCT05566041]Phase 3292 participants (Anticipated)Interventional2022-08-01Active, not recruiting
P-RAD: A Randomized Study of Preoperative Chemotherapy, Pembrolizumab and No, Low or High Dose RADiation in Node-Positive, HER2-Negative Breast Cancer [NCT04443348]Phase 2120 participants (Anticipated)Interventional2020-12-16Recruiting
A Randomized Phase II Study of Bortezomib Plus ICE (BICE) Versus Standard ICE for Patients With Relapsed/Refractory Classical Hodgkin Lymphoma [NCT00967369]Phase 220 participants (Actual)Interventional2009-08-24Completed
Fudan University Shanghai Cancer Center Breast Cancer Precision Platform Series Study- Neoadjuvant Therapy (FASCINATE-N) [NCT05582499]Phase 1/Phase 2716 participants (Anticipated)Interventional2022-11-01Recruiting
Phase II Study of Accelerated and Adaptive Radiation Therapy for Locally-Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT03128008]Phase 210 participants (Actual)Interventional2017-12-07Completed
Chemoradiation Plus tisLelizumAb for Conversion Therapy of Locally Nonresectable ESCC [NCT05394415]Phase 1/Phase 230 participants (Anticipated)Interventional2022-05-01Recruiting
A Phase 1B/2 Multicohort Umbrella Study to Evaluate the Safety and Efficacy of Novel Treatments And/Or Combinations of Treatments in Participants With Ovarian Cancer (OPAL) [NCT03574779]Phase 1/Phase 2125 participants (Anticipated)Interventional2018-11-15Recruiting
A Phase II Randomized Trial of Carboplatin and Topotecan; Flavopiridol, Mitoxantrone and Cytosine Arabinoside; and Sirolimus, Mitoxantrone, Etoposide and Cytosine Arabinoside for the Treatment of Adults With Primary Refractory or Initial Relapse of Acute [NCT00634244]Phase 292 participants (Actual)Interventional2008-10-31Completed
Phase 2 Study to Evaluate the Pharmacokinetics and Drug-Drug Interaction of Cetuximab and Carboplatin in Patients With Advanced Solid Tumors [NCT01063075]Phase 234 participants (Actual)Interventional2010-06-30Completed
A Master Protocol of Phase 1/2 Studies of Nivolumab in Advanced NSCLC Using Nivolumab as Maintenance After Induction Chemotherapy or as First-line Treatment Alone or in Combination With Standard of Care Therapies (CheckMate 370: CHECKpoint Pathway and niv [NCT02574078]Phase 1/Phase 2341 participants (Actual)Interventional2015-11-23Completed
A Phase I, Open-Label, 2 Part Multicentre Study to Assess the Safety, Tolerability and Efficacy of Olaparib in Combination With Carboplatin: Part A: Dose Escalation of Olaparib in Combination With Carboplatin in Patients With Advanced HER-2 Negative Breas [NCT02561832]Phase 115 participants (Actual)Interventional2015-11-06Terminated(stopped due to This decision was based upon strategic considerations impacting the clinical development of olaparib in this indication.)
A Randomized Phase III Double Blind Trial Evaluating Selective COX-2 Inhibition in COX-2 Expressing Advanced Non-Small Cell Lung Cancer [NCT01041781]Phase 3313 participants (Actual)Interventional2010-02-28Terminated(stopped due to DSMB recommendation)
Feasibility Study of SBRT Plus Chemotherapy for Non-Small Cell Lung Carcinoma [NCT02319889]Early Phase 13 participants (Actual)Interventional2016-02-02Terminated(stopped due to Funding unavailable)
Phase I Evaluation of Intravenous Carboplatin With Weekly Paclitaxel and Bevacizumab in Patients Undergoing Neoadjuvant Chemotherapy for Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer [NCT01219777]Phase 19 participants (Actual)Interventional2010-09-30Completed
A Randomized Phase II Trial of Selumetinib in Patients Receiving Standard Pemetrexed and Platinum-based Chemotherapy for the Treatment of Advanced or Metastatic KRAS Wildtype or Unknown Non-Squamous Non-Small Cell Lung Cancer [NCT02337530]Phase 262 participants (Actual)Interventional2015-02-05Completed
A Phase 1b Dose-escalation Study of TRC105 in Combination With Paclitaxel/Carboplatin and Bevacizumab in Patients With Stage 4 Non-Squamous Cell Lung Cancer [NCT03780010]Phase 115 participants (Actual)Interventional2015-09-30Completed
A Phase II Study of Pre-operative Panitumumab, Paclitaxel, Carboplatin and Continuous Infusion 5FU in the Treatment of Potentially Resectable Gastroesophageal Adenocarcinoma [NCT01182610]Phase 21 participants (Actual)Interventional2011-04-30Terminated(stopped due to Safety concern in a similar trial enrolling the same patient population)
High Dose Conditioning With Ifosfamide, Carboplatin, and Etoposide With Autologous Stem Cell Transplantation for Patients With Recurrent Nasopharyngeal Carcinoma [NCT02137096]Phase 31 participants (Actual)Interventional2014-06-30Terminated(stopped due to This is a rare disease, and enrollment was poor.)
A Phase III, Randomized, Double-Blind, Placebo-Controlled Multi-Center Study of ASA404 in Combination With Paclitaxel and Carboplatin as First-Line Treatment for Locally Advanced or Metastatic (Stage IIIb/IV) Non-Small Cell Lung Cancer (NSCLC) [NCT00662597]Phase 31,285 participants (Actual)Interventional2008-04-30Terminated
A Randomized Phase II Trial of Carboplatin With or Without Nivolumab in First-line Metastatic Triple-negative Breast Cancer [NCT03414684]Phase 278 participants (Actual)Interventional2018-01-30Active, not recruiting
A Phase II Trial of Carboplatin and Paclitaxel in Patients With Metastatic, Castrate-Resistant Prostate Cancer Previously Treated With Docetaxel [NCT01558492]Phase 23 participants (Actual)Interventional2011-03-31Terminated(stopped due to Poor accrual)
A Pilot Study Evaluating the Feasibility of an Intercontinental Phase III Chemotherapy Study for Patients With Choroid Plexus Tumors [NCT00500890]Phase 32 participants (Actual)Interventional2005-09-02Terminated(stopped due to PI has left the institution)
Treatment of Stage IV Breast Cancer With Activated T Cells After Peripheral Blood Stem Cell Transplant (Pilot Phase II) [NCT00020722]Phase 27 participants (Actual)Interventional2007-08-31Terminated(stopped due to Lack of funding to continue study.)
Phase II Study of Stereotactic Body Radiotherapy (SBRT) and Chemotherapy for Unresectable Cholangiocarcinoma Followed by Liver Transplantation [NCT01151761]Phase 22 participants (Actual)Interventional2011-01-31Terminated(stopped due to Poor accrual)
A Multicenter, Open-label, Phase II Study of AK104（an Anti-PD-1 and Anti-CTLA-4 Bispecific Antibody) in the Treatment of Recurrent or Metastatic Cervical Cancer [NCT04868708]Phase 250 participants (Actual)Interventional2021-04-01Active, not recruiting
INTERNATIONAL RANDOMIZED STUDY FOR THE SALVAGE TREATMENT OF GERM CELL TUMOURS [NCT00002566]Phase 3280 participants (Anticipated)Interventional1994-02-28Completed
RANDOMIZED MULTIINSTITUTIONAL PHASE III TRIAL OF BEP AND HIGH DOSE CHEMOTHERAPY VERSUS BEP ALONE IN PREVIOUSLY UNTREATED PATIENTS WITH POOR RISK GERM CELL TUMORS [NCT00002596]Phase 3270 participants (Anticipated)Interventional1994-09-30Completed
Phase I Pilot Study of Multiple Cycles of High Dose Chemotherapy With Peripheral Blood Stem Cell Infusions In Advanced Stage Neuroblastoma [NCT00002740]Phase 130 participants (Anticipated)Interventional1996-05-31Completed
A Phase I Study Evaluating Copanlisib in Combination With R-GCD (Gemcitabine, Carboplatin, Dexamethasone, and Rituximab) With Relapsed/Refractory Diffuse Large B-Cell Lymphoma and High-Risk Follicular Lymphoma [NCT04156828]Phase 112 participants (Actual)Interventional2020-03-31Terminated(stopped due to Terminated due to low accrual)
A Phase II Study of Carboplatin Plus Pemetrexed Plus Atezolizumab Plus Bevacizumab in Chemotherapy and Immunotherapy-naïve Patients With Stage IV Non-squamous Non-small Cell Lung Cancer: Big Ten Cancer Research Consortium BTCRC-LUN17-139 [NCT03713944]Phase 230 participants (Actual)Interventional2018-11-15Terminated(stopped due to Extreme toxicity, thromboembolic events)
Phase I/II Study of Weekly Intravenous Estramustine Phosphate in Combination With Paclitaxel and Carboplatin in Patients With Advanced Prostate Cancer [NCT00003394]Phase 1/Phase 218 participants (Anticipated)Interventional1998-04-30Completed
Chemotherapy for Progressive Low Grade Astrocytoma in Children Less Than Ten Years Old [NCT00002944]Phase 3428 participants (Actual)Interventional1997-04-30Completed
A Phase I-II Intensive-Dose Ifosfamide, Carboplatin and Taxotere (IC-T) Combination Chemotherapy Followed by Autologous Stem Cell Rescue for Patients With Refractory Malignancies [NCT00003406]Phase 1/Phase 230 participants (Anticipated)Interventional1997-10-31Completed
A Randomized Phase II Study of Progression Free Survival Comparing Gemcitabine (1000 mg/m2 Infusion) Versus Carboplatin (AUC5 Infusion) Plus Alimta (500 mg/m2 Infusion) as First-line Chemotherapy in Elderly Patients With Locally Advanced (Stage IIIb) or M [NCT00754364]Phase 2108 participants (Actual)Interventional2008-10-31Terminated(stopped due to low enrollment rate)
Phase I-II Study of Tandem Cycles of High Dose Chemotherapy Followed by Autologous Hematopoietic Stem Cell Support in Women With Persistent, Refractory or Recurrent Advanced (Stage III or IV), Epithelial Ovarian Cancer [NCT00003064]Phase 1/Phase 230 participants (Anticipated)Interventional1997-01-31Active, not recruiting
Evaluation of Chemotherapy as Initial Treatment for Retinoblastoma [NCT00002794]Phase 225 participants (Actual)Interventional1996-02-29Completed
PHASE I PILOT STUDY OF SEQUENTIAL HIGH DOSE CYCLES OF CISPLATIN, CYCLOPHOSPHAMIDE, ETOPOSIDE AND IFOSFAMIDE, CARBOPLATIN AND TAXOL WITH AUTOLOGOUS STEM CELL SUPPORT [NCT00002854]Phase 133 participants (Actual)Interventional1994-12-31Completed
Randomized Trial on Chemosensitivity Testing in Advanced Primary Ovarian Carcinoma (Phase III) [NCT00003214]Phase 3300 participants (Anticipated)Interventional1996-07-31Completed
Intergroup Protocol for Treatment of Children With Hepatoblastoma [NCT00003994]Phase 3277 participants (Actual)Interventional1999-03-31Completed
Treatment for Extrachoroidal or Metastatic Retinoblastoma [NCT00004006]Phase 24 participants (Actual)Interventional1997-11-30Completed
A Phase 1 Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of Second Mitochondrial-derived Activator of Caspases Mimetic BGB-24714 as Monotherapy and With Combination Therapies in Patient [NCT05381909]Phase 1168 participants (Anticipated)Interventional2022-07-06Recruiting
Phase I Trial of High Dose Chemotherapy Using Amifostine for In-Vivo Protection of GM-CSF Primed Progenitor Cells [NCT00004036]Phase 130 participants (Anticipated)Interventional1997-11-30Active, not recruiting
Effect of an Early Therapeutic Permutation on the Tumoral Control of Patients Receiving in First Line a Specific Inhibitor of Tyrosin Kinase of EGFR (Erlotinib) or a Taxan-based Chemotherapy for the Treatment of Not Resecable Adenocarcinoma With Bronchiol [NCT00384826]Phase 2133 participants (Actual)Interventional2006-09-30Completed
An Open-Label, Phase III Study of Platinum-Gemcitabine With or Without Nivolumab in the First-Line Treatment of Recurrent or Metastatic Nasopharyngeal Carcinoma [NCT04458909]Phase 315 participants (Actual)Interventional2020-12-09Terminated(stopped due to External information)
A Randomized Study Comparing Carboplatin and Thalidomide With Carboplatin Alone in Patients With Stage Ic - IV Ovarian Cancer [NCT00004876]Phase 230 participants (Anticipated)Interventional1999-08-31Completed
A Phase II/III Trial of Chemotherapy Alone Versus Chemotherapy Plus SCH 58500 in Newly Diagnosed Stage III Ovarian and Primary Peritoneal Cancer Patients With Greater Than or Equal to 0.5 cm and Less Than or Equal to 2 cm Residual Disease Following Surger [NCT00003880]Phase 2/Phase 3132 participants (Actual)Interventional1999-02-28Terminated
A Phase II Pilot Study of Sequential High Dose Chemotherapy and CD 34+ Selected Stem Cell Support Without Conventional-Dose Induction Chemotherapy for Women With Metastatic Breast Cancer [NCT00004900]Phase 20 participants Interventional1999-10-31Completed
A Phase II Multi-Institution Study of Docetaxel and Doxorubicin as Induction Therapy Followed by Sequential High Dose Chemotherapy and CD 34+ Selected Stem Cell Support for Women With Metastatic Breast Cancer [NCT00004906]Phase 20 participants Interventional1999-10-31Completed
A Randomized Controlled, Open-label, Multicenter Clinical Study of Pyrotinib Maleate Combined With Trastuzumab,Dalpiciclib, and Letrozole Versus Trastuzumab Combined With Pertuzumab, Docetaxel, and Carboplatin as Neoadjuvant Therapy for Stage II-III HR +/ [NCT05638594]Phase 2236 participants (Anticipated)Interventional2022-12-20Recruiting
Phase III Double-blind Randomized Placebo Controlled Trial of Atezolizumab in Combination With Paclitaxel and Carboplatin in Women With Advanced/Recurrent Endometrial Cancer [NCT03603184]Phase 3550 participants (Anticipated)Interventional2018-10-02Active, not recruiting
Phase I/IIA Study of Sequential Ifosfamide and Topotecan in Patients With Small Cell Lung Cancer [NCT00004186]Phase 1/Phase 255 participants (Anticipated)Interventional1996-12-31Completed
A Phase I Feasibility Trial of Carboplatin and Topotecan Followed by Carboplatin and Paclitaxel (Sequential Doublets) in Patients With Previously Untreated Epithelial Ovarian Carcinoma and Primary Peritoneal Carcinoma [NCT00005026]Phase 10 participants Interventional2000-02-29Completed
Phase I Study of Concurrent Cereport and Carboplatin With Radiation Therapy for Children With Newly-Diagnosed Brain Stem Gliomas [NCT00005602]Phase 113 participants (Actual)Interventional2001-02-28Completed
A Pilot Trial of Daily Oral ZD1839 (Iressa) With Standard Doses of Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer [NCT00005806]Phase 10 participants Interventional1999-09-30Completed
Adjuvant Treatment of Cancer of the Esophagus or Cardia Before Resection With Curative Intent. Comparative Study Between Chemotherapy and Radiochemotherapy [NCT01362127]Phase 2181 participants (Actual)Interventional2006-10-31Completed
A Randomized Phase II Study of Radiation Therapy, Pemetrexed and Carboplatin With or Without Cetuximab in Stage III Non-Small Cell Lung Cancer [NCT00117962]Phase 2109 participants (Actual)Interventional2005-09-30Completed
A Phase II Trial of Induction Carboplatin and Docetaxel Followed by Radiotherapy Then Consolidation Chemotherapy With Carboplatin and Docetaxel in Stage III, IV and Recurrent Endometrial Cancer [NCT00258362]Phase 241 participants (Actual)Interventional2005-07-31Completed
Nivolumab With Chemotherapy in Pleural Mesothelioma After Surgery [NCT04177953]Phase 292 participants (Actual)Interventional2019-02-04Active, not recruiting
Risk-Adapted Therapy for Young Children With Embryonal Brain Tumors, Choroid Plexus Carcinoma, High Grade Glioma or Ependymoma [NCT00602667]Phase 2293 participants (Actual)Interventional2007-12-17Active, not recruiting
Multicenter Phase II Study for International Intraocular Retinoblastoma Classification Groups B, C & D Tumors Treated With Carboplatin-Etoposide-Vincristine-Cyclosporine-Focal Therapy Multimodality Protocol (OCRN Multicenter RB 2003) [NCT00110110]Phase 271 participants (Anticipated)Interventional2004-06-30Active, not recruiting
A Phase I/II Study of Paclitaxel, Carboplatin and YM155 (Survivin Suppressor) in Subjects With Solid Tumors (Phase I) and Advanced Non-Small Cell Lung Carcinoma (Phase II) [NCT01100931]Phase 1/Phase 242 participants (Actual)Interventional2010-02-28Completed
Phase II Evaluation of Cetuximab (C225) Combined With Induction Paclitaxel and Carboplatin Followed by C225, Paclitaxel, Carboplatin, and Radiation for Stage III/IV Operable Squamous Cancer of the Head and Neck [NCT00089297]Phase 274 participants (Actual)Interventional2005-01-06Completed
A Multicenter, Open-Label, Non-Comparative, Three-Arm, Phase IIa Trial of Ipatasertib (GDC-0068) in Combination With Non-Taxane Chemotherapy Agents for Taxane-Pretreated Unresectable Locally Advanced or Metastatic TNBC Patients [NCT04464174]Phase 254 participants (Actual)Interventional2020-10-08Completed
Phase I Trial of Ribociclib (Ribociclib (LEE-011)) With Platinum-based Chemotherapy in Recurrent Platinum Sensitive Ovarian Cancer [NCT03056833]Phase 135 participants (Actual)Interventional2017-06-10Completed
Nivolumab Plus Weekly Carboplatin and Paclitaxel as Induction in Resectable Locally Advanced Head and Neck Cancer [NCT03342911]Phase 234 participants (Actual)Interventional2017-11-13Completed
Phase I/II Trial of Venetoclax in Combination With R-ICE (V+RICE) Chemotherapy for Relapsed/Refractory Diffuse Large B-Cell Lymphoma [NCT03064867]Phase 1/Phase 265 participants (Actual)Interventional2017-06-26Active, not recruiting
A Phase II Study of Induction Chemotherapy Followed by Surgical Treatment in Locally Advanced Oropharyngeal And Supraglotic Cell Carcinoma [NCT02760667]Phase 220 participants (Actual)Interventional2015-06-30Active, not recruiting
High-dose 131I-MIBG Treatment Incorporated Into Tandem High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With High-risk Neuroblastoma [NCT03061656]Phase 240 participants (Anticipated)Interventional2009-01-01Active, not recruiting
A Randomized, Double-blind Phase 2 Study Comparing Gemcitabine and Cisplatin in Combination With OGX-427 or Placebo in Patients With Advanced Transitional Cell Carcinoma [NCT01454089]Phase 2183 participants (Actual)Interventional2011-10-31Completed
A Phase III, Randomized, Two-armed, Parallel, Triple-blind, Active-controlled, Equivalency Clinical Trial of Efficacy and Safety Pertuzumab® (CinnaGen Co.) Compared With Perjeta® (Originator Pertuzumab) in Neoadjuvant Treatment of HER2+ Breast Cancer [NCT04957212]Phase 3214 participants (Actual)Interventional2018-08-11Completed
A Randomized, Open-label, Single-center, Phase III Trial Comparing Docetaxel Plus Carboplatin (TCb) Versus Epirubicin Plus Cyclophosphamide Followed by Docetaxel (EC-T) Regimen as Adjuvant Chemotherapy in Patients With LN≥4 Estrogen Receptor Positive and [NCT05901428]Phase 31,736 participants (Anticipated)Interventional2023-06-01Recruiting
A Phase 1/2 Study of the Highly Selective EGFR Inhibitor, BLU-701, in Patients With EGFR-Mutant Non-Small Cell Lung Cancer [NCT05153408]Phase 120 participants (Actual)Interventional2022-01-13Terminated(stopped due to Lack of efficacy)
Canadian Multi-arm Multi-stage Randomized Controlled Trial Assessing Front Line Treatment in Serous or p53 Mutant Endometrial Cancer [NCT04159155]Phase 2/Phase 3120 participants (Anticipated)Interventional2020-11-17Suspended(stopped due to Low accrual, protocol amendment in progress , to be re-opened soon.)
Durvalumab (MEDI4736) in Frail and Elder Patients With Metastatic NSCLC (DURATION) [NCT03345810]Phase 2200 participants (Actual)Interventional2017-12-14Completed
An Open-Label, Multicenter, Phase 1/2 Study of Poly(ADP-Ribose) Polymerase (PARP) Inhibitor E7449 as Single Agent in Subjects With Advanced Solid Tumors or With B-cell Malignancies and in Combination With Temozolomide (TMZ) or With Carboplatin and Paclita [NCT01618136]Phase 1/Phase 241 participants (Actual)Interventional2012-01-31Completed
Phase I/II Pilot Study of Lapatinib in Combination With Carboplatin and Paclitaxel in the Treatment of Recurrent/Metastatic Adenocarcinoma of the Esophagus and Gastroesophageal Junction (GEJ) [NCT01395537]Phase 1/Phase 213 participants (Actual)Interventional2011-08-31Terminated(stopped due to Research Cancelled)
Selected Chemotherapy Combined Immunotherapy Treated High Risk Patient After Neoadjuvant Chemoradiotherapy in Resected Locally Advanced Esophageal Squamous Cell Carcinoma: an Exploratory Study [NCT05189730]Phase 280 participants (Anticipated)Interventional2021-07-01Recruiting
Exploratory Study Evaluating the Potential of Immune Signature Profiling for Predicting Response in Patients With Resectable Stage II, IIIA and Select IIIB (T3N2 Only) Non-squamous Non-Small Cell Lung Cancer (NSCLC) to Neoadjuvant ATEZOLIZUMAB Plus Carbop [NCT04865250]Phase 220 participants (Anticipated)Interventional2021-01-07Recruiting
A Study of QL1604 Plus Chemotherapy Versus Chemotherapy Plus Placebo With Stage ⅣB, Recurrent, or Metastatic Cervical Cancer [NCT04864782]Phase 2/Phase 3458 participants (Anticipated)Interventional2020-09-23Recruiting
Sintilimab Combined With Anlotinib Hydrochloride and Standard Platinum-Containing Dual-Agent Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) as First-Line Treatment: A Single-Arm, Prospective and Exploratory Clinical Study [NCT04846452]Phase 240 participants (Anticipated)Interventional2021-06-01Recruiting
Adjuvant Toripalimab Versus Placebo Combined With Chemotherapy for EGFR/ALK Mutation Negative Stage II-IIIB(N2) Non-small-cell Lung Cancer (LungMate-008): a Randomised, Double-blind, Controlled, Phase 3 Trial [NCT04772287]Phase 3341 participants (Anticipated)Interventional2021-03-31Not yet recruiting
Open-label, Multicenter Phase I/II Study: Salvage Therapy of Progressive and Relapsed Aggressive Non-Hodgkin-Lymphoma by Combination of Lenalidomide (Revlimid®) With Rituximab, Dexamethason, High-dose ARA-C and Cisplatinum (R²-DHAP) [NCT02983097]Phase 1/Phase 234 participants (Actual)Interventional2010-11-30Terminated(stopped due to Phase II: no scientific interests are given anymore)
A Neoadjuvant Study of Sintilimab Plus Platinum Doublet Chemotherapy in IIIA(N2) Stage Non-Small Cell Lung Cancer (NSCLC) [NCT04840290]Phase 330 participants (Anticipated)Interventional2019-06-01Recruiting
A Phase II,Randomized Study of Adjuvant Chemotherapy of Three-step Regimens (ACTS) in Stage IIIc and Stage IV Epithelial Ovarian, Fallopian Tube, and Primary Peritoneal Cancer (EOC, FTC, PPC) [NCT02562365]Phase 2130 participants (Anticipated)Interventional2015-11-30Active, not recruiting
Neoadjuvant Therapy Study Guided by Drug Screening in Vitro Patient-derived Tumor-like Cell Clusters for Human Epidermal Growth Factor Receptor 2 (HER2) Negative Early Breast Cancer Patients [NCT04836156]Phase 1/Phase 246 participants (Anticipated)Interventional2021-04-02Recruiting
Evaluation of the Immunogenicity of Vaccination With Synthetic Peptides in Adjuvant in Patients With Advanced Ovarian, Primary Peritoneal, or Fallopian Tube Cancer [NCT00373217]Phase 26 participants (Actual)Interventional2006-04-13Terminated(stopped due to Slow enrollment rate.)
A Multi-arm Phase I Safety Study of Nivolumab in Combination With Gemcitabine/Cisplatin, Pemetrexed/Cisplatin, Carboplatin/Paclitaxel, Bevacizumab Maintenance, Erlotinib, Ipilimumab or as Monotherapy in Subjects With Stage IIIB/IV Non-small Cell Lung Canc [NCT01454102]Phase 1472 participants (Actual)Interventional2011-12-16Completed
Treatment of Locally Advanced VULvar CArcinoma in a Neoadjuvant Setting With Carboplatin and Paclitaxel Chemotherapy (VULCANize) [NCT04192253]Phase 251 participants (Anticipated)Interventional2020-01-14Recruiting
Phase II Trial of Toripalimab, an Anti-PD-1 Monoclonal Antibody, in Combination With Combination Carboplatin and Nab-paclitaxel , as a Novel Neoadjuvant Pre-Surgical Therapy for Salivary Gland Malignant Neoplasms [NCT04825938]Phase 215 participants (Anticipated)Interventional2021-04-30Not yet recruiting
A Phase II Study of PD-1 Antibody Plus Neoadjuvant Chemotherapy for Advanced-stage Ovarian Cancer (Z2HOC-01) [NCT04815408]Phase 240 participants (Anticipated)Interventional2021-04-01Recruiting
A Randomized, Open-Label Phase 2 Study of Denintuzumab Mafodotin (SGN-CD19A) Plus Rituximab, Ifosfamide, Carboplatin, and Etoposide (19A+RICE) Chemotherapy vs. RICE in the Treatment of Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DL [NCT02592876]Phase 281 participants (Actual)Interventional2015-10-31Terminated(stopped due to Sponsor decision based on portfolio prioritization)
Phase 3 Trial, Randomized, Open-Label, of NOV-002 in Combination With Paclitaxel and Carboplatin vs. Paclitaxel and Carboplatin Alone for the Treatment of Advanced Non-Small-Cell Lung Cancer (NSCLC) [NCT00347412]Phase 3903 participants (Actual)Interventional2006-11-30Completed
Phase II Trial of Concurrent Irinotecan, Carboplatin and Radiation Therapy Followed by Bevacizumab (Avastin) in the Treatment of Patients With Limited Stage Small Cell Lung Cancer [NCT00193375]Phase 260 participants (Actual)Interventional2003-08-31Completed
A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL] [NCT00095875]Phase 3145 participants (Actual)Interventional2004-08-31Completed
Phase II Study Of Neo-Adjuvant Paclitaxel, Estramustine And Carboplatin (TEC) Plus Androgen Ablation Prior To Radiation Therapy In Patients With Poor Prognosis Localized Prostate Cancer [NCT00016913]Phase 234 participants (Actual)Interventional2001-05-31Completed
A Randomized, Open Label, Phase III Study of Overall Survival Comparing Pembrolizumab (MK-3475) Versus Platinum Based Chemotherapy in Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer (Keynote 042) [NCT02220894]Phase 31,274 participants (Actual)Interventional2014-10-30Completed
A Single Arm Phase II Trial Evaluating the Efficacy and Safety of Bevacizumab, Carboplatin, Gemcitabine and Atezolizumab in Early Relapsing Metastatic Triple Negative Breast Cancer [NCT04739670]Phase 231 participants (Anticipated)Interventional2021-03-01Recruiting
A Study of Pembrolizumab (MK-3475) Plus Platinum and Gemcitabine as First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (PIPER) [NCT05286619]Phase 263 participants (Anticipated)Interventional2022-09-22Recruiting
Phase 2 Trial of Neoadjuvant and Adjuvant Tiragolumab Plus Atezolizumab in Patients With Newly Diagnosed PD-L1 CPS Positive Resectable Stage 3-4 Oral Cavity Squamous Cell Carcinoma (OCSCC). [NCT05681039]Phase 229 participants (Anticipated)Interventional2023-06-02Recruiting
Risk-Adapted Therapy for Patients With Untreated Age-Adjusted International Prognostic Index II or III Diffuse Large B Cell Lymphoma [NCT00039195]Phase 298 participants (Actual)Interventional2006-11-30Completed
A Phase II Trial of Concurrent Docetaxel (Taxotere) / Carboplatin / Radiotherapy Followed by Surgical Resection Followed by Consolidation Taxotere / Carboplatin in Stage III Non-Small Cell Lung Cancer (NSCLC) [NCT00238615]Phase 213 participants (Actual)Interventional2003-03-31Terminated(stopped due to low accrual)
A Phase II, Open-Label, Non-Randomized, Pilot Study of Paclitaxel, Carboplatin and Oral Metformin for Patients Newly Diagnosed With Stage II-IV Epithelial Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma [NCT02437812]Phase 230 participants (Anticipated)Interventional2014-01-31Recruiting
A Multicenter Phase II Trial of Induction Nimotuzumab Plus Gemcitabine and Carboplatin Followed by Surgery in Patients With Unresectable Stage III Squamous Cell Lung Carcinoma [NCT02428764]Phase 237 participants (Anticipated)Interventional2015-04-30Recruiting
I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma [NCT00253435]Phase 250 participants (Actual)Interventional2005-09-30Completed
Phase II Trial Of Induction Chemotherapy Followed By Attenuated Chemoradiotherapy For Locally Advanced Head And Neck Squamous Cell Carcinoma Associated With Human Papillomavirus (HPV) [NCT01716195]Phase 218 participants (Actual)Interventional2012-10-31Completed
Randomized, Phase II Study of Pembrolizumab (MK-3475) Versus Chemotherapy in Patients With Advanced Melanoma (KEYNOTE 002) [NCT01704287]Phase 2540 participants (Actual)Interventional2012-11-20Completed
An Adaptive, Randomized Phase II Trial to Determine Pathologic Complete Response With the Addition of Carboplatin With and Without Veliparib to Standard Chemotherapy in the Neoadjuvant Treatment of Triple-Negative Breast Cancer [NCT01818063]Phase 29 participants (Actual)Interventional2013-04-25Completed
Phase II Trial of Cetuximab Alone and in Combination With Carboplatin in ER-Negative, PR-Negative, HER-2 Nonoverexpressing Metastatic Breast Cancer [NCT00232505]Phase 2112 participants (Actual)Interventional2005-11-30Completed
Phase II Trial of Neoadjuvant Therapy With Carboplatin and Gemcitabine With Thalidomide in Patients With Stage II and IIIA Non-Small Cell Lung Cancer [NCT00281827]Phase 222 participants (Actual)Interventional2002-05-31Terminated(stopped due to Due to drug unavailability)
A Randomized Phase II Trial Comparing Two Doses of Pulsed Erlotinib Prechemotherapy (PEP-C) in Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer [NCT00287989]Phase 286 participants (Actual)Interventional2004-11-30Completed
A Phase II Trial of Intraperitoneal Paclitaxel and Carboplatin Therapy in the Treatment of Women With Newly Diagnosed, Optimally Cytoreduced Carcinoma of Mullerian Origin [NCT00181701]Phase 246 participants (Actual)Interventional2004-10-31Completed
A Phase II Study of ZD6474 Alone and With Chemotherapy in Advanced NSCLC [NCT00290537]Phase 24 participants (Actual)Interventional2006-01-31Terminated(stopped due to Accrual was suboptimal and increasing the number of patients was not feasible.)
A Phase 3 Randomized, Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the PARP Inhibitor Veliparib (ABT-888) in HER2-Negative Metastatic or Locally Advanced Unresectable BRCA-Associated Breast Cancer [NCT02163694]Phase 3509 participants (Actual)Interventional2014-07-17Active, not recruiting
Assessing the REsponse Rate of Weekly Neo-adjuvanT pacliTAxel (Taxol) in Nigerian Women With Breast Cancer (ARETTA) [NCT03058939]Phase 20 participants (Actual)Interventional2018-11-30Withdrawn(stopped due to Study never activated to enrollment.)
Induction Therapy With Chemoimmunotherapy Followed by Surgery for Unresectable Stage III Non-small Cell Lung Cancer: a Single-center, Single-arm, Prospective Clinical Study [NCT04943029]Phase 230 participants (Anticipated)Interventional2021-08-20Recruiting
Phase 1b/2a Study Investigating ATX-101 in Combination With Platinum-based Chemotherapy in Platinum-sensitive, Recurrent Ovarian, Fallopian Tube and Primary Peritoneal Cancer [NCT04814875]Phase 1/Phase 278 participants (Anticipated)Interventional2021-09-01Recruiting
Neo - Adjuvant Chemo / Immunotherapy for the Treatment of Resectable Stage IIIA Non Small Cell Lung Cancer (NSCLC): A Phase II Multicenter Exploratory Study [NCT03081689]Phase 246 participants (Actual)Interventional2017-04-15Active, not recruiting
Phase II Trial of Lazertinib and Pemetrexed/Carboplatin Combination in Patients With EGFR Positive, Metastatic NSCLC With Asymptomatic or Mild Symptomatic Brain Metastases After Failure of Osimertinib [NCT05477615]Phase 228 participants (Anticipated)Interventional2022-08-31Not yet recruiting
A Randomized Phase II Trial of Combination Versus Single Agent Chemotherapy in High-risk Elderly Patients With Advanced Non-small Cell Lung Cancer [NCT02590003]Phase 23 participants (Actual)Interventional2015-11-30Terminated(stopped due to Trial was stopped after non-response to treatment.)
Prospective Phase ii Clinical Study of the Efficacy and Safety of Durvalumab Combined With Consolidation Radiotherapy After First-line Treatment With Platinum-containing Chemotherapy in Extensive Stage Small Cell Lung Cancer With Oligometastases (1-5 Lesi [NCT05484583]Phase 258 participants (Anticipated)Interventional2022-08-01Not yet recruiting
QL1706 Combined With Platinum-based Chemotherapy Versus Placebo Combined With Platinum-based Chemotherapy as Adjuvant Therapy for Stage II-IIIB Non-small Cell Lung Cancer After Complete Surgical Resection: a Randomized, Double-blind, Multicenter Phase III [NCT05487391]Phase 3632 participants (Anticipated)Interventional2022-10-01Not yet recruiting
LCI-LUN-ABR-001: A Pilot Study of Carboplatin With Nab-Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer of Squamous Histology [NCT02328105]Phase 211 participants (Actual)Interventional2014-12-31Completed
A Phase III Randomized, Open-label, Multi-center, Global Study of MEDI4736 Alone or in Combination With Tremelimumab Versus Standard of Care in the Treatment of First-line Recurrent or Metastatic Squamous Cell Head and Neck Cancer Patients [NCT02551159]Phase 3823 participants (Actual)Interventional2015-10-15Completed
A Phase II Study of RRx-001 in Platinum Refractory/Resistant Small Cell Carcinoma, EGFR TKI Resistant EGFR+ T790M Negative Non-Small Cell Lung Cancer, High Grade Neuroendocrine Tumors and Resistant/Refractory Ovarian Cancer Prior to Re-administration of P [NCT02489903]Phase 2139 participants (Actual)Interventional2015-06-30Completed
DREAM3R: DuRvalumab (MEDI4736) With chEmotherapy as First Line treAtment in Advanced Pleural Mesothelioma - A Phase 3 Randomised Trial [NCT04334759]Phase 3214 participants (Actual)Interventional2021-02-18Active, not recruiting
Randomized, Multicenter, Phase II/III Study, Evaluating Fractionated Cisplatin Chemotherapy/Gemcitabine Versus Carboplatin/Gemcitabine in the Treatment of Advanced or Metastatic Urothelial Cancer With Impaired Renal Function. [NCT02240017]Phase 2/Phase 346 participants (Actual)Interventional2015-01-21Completed
GUARDIAN-1 Trial: A Phase 1 Study of Ganetespib in Combination With Chemoradiation for Stage II-III Esophageal Carcinoma [NCT02389751]Phase 13 participants (Actual)Interventional2015-04-10Completed
I-CURE-1: A Phase II, Single Arm Study of Pembroluzimab Combined With Carboplatin in Patients With Circulating Tumor Cells (CTCs) Positive Her-2 Negative Metastatic Breast Cancer (MBC) [NCT03213041]Phase 2100 participants (Anticipated)Interventional2017-09-14Recruiting
A Dose-Finding Study Of Afatinib In Combination With Cisplatin Or Carboplatin + Pemetrexed In Patients With EGFR-Mutant Lung Cancers Undergoing Definitive Chemoradiation [NCT01836341]Phase 10 participants (Actual)Interventional2013-04-30Withdrawn
Phase III Trial of Single-Agent Pemetrexed (Alimta®) Versus the Combination of Carboplatin and Pemetrexed in Patients With Advanced Non-small-cell Lung Cancer and Performance Status of 2 [NCT01836575]Phase 3228 participants (Actual)Interventional2008-04-30Completed
Phase I Study of Induction Chemotherapy With Afatinib, Ribavirin, and Weekly Carboplatin/Paclitaxel for Stage IVA/IVB HPV Associated Oropharynx Squamous Cell Cancer (OPSCC) [NCT01721525]Phase 110 participants (Actual)Interventional2012-11-30Completed
Efficacy and Safety of First-line Etoposide/Platinum-based Chemotherapy Followed by Toripalimab Combined With Anlotinib for Maintenance in Extensive Small Cell Lung Cancer: A Single-arm, Multicentral Phase II Study [NCT04363255]Phase 220 participants (Anticipated)Interventional2020-05-01Not yet recruiting
An Open-label, Safety and Tolerability Phase 1b Trial of CAN04, a Fully Humanized Anti-IL1RAP Monoclonal Antibody, and Pembrolizumab in Combination With and Without Carboplatin and Pemetrexed in Subjects With Solid Tumors [NCT04452214]Phase 119 participants (Actual)Interventional2020-09-24Completed
Dasatinib With Ifosfamide, Carboplatin, Etoposide: A Pediatric Phase I/II Trial [NCT00788125]Phase 1/Phase 27 participants (Actual)Interventional2008-09-03Terminated(stopped due to Terminated early due a shift in resources after lackluster performance of the drug.)
Weekly Docetaxel, Cisplatin, and Cetuximab (TPC) in Palliative Treatment of Patients With SCCHN [NCT01437449]Phase 227 participants (Actual)Interventional2011-10-31Completed
A Phase 3, Randomized, Double-Blind Study of Trilaciclib or Placebo in Patients Receiving First- or Second-Line Gemcitabine and Carboplatin Chemotherapy for Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (PRESERVE 2) [NCT04799249]Phase 3194 participants (Actual)Interventional2021-04-15Active, not recruiting
Neoadjuvant PD-1 Inhibitor (Tislelizumab) Plus Chemotherapy in Patients With Limited-stage Small-cell Lung Cancer: an Open-lable, Single-arm, Phase 2 Trial [NCT04542369]Phase 215 participants (Anticipated)Interventional2021-05-01Recruiting
Adjuvant Treatment in Extensive Unilateral Retinoblastoma Primary Enucleated [NCT02870907]Phase 2185 participants (Anticipated)Interventional2010-03-31Recruiting
A Phase II Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel or Carboplatin and Gemcitabine in Platinum-sensitive, Recurrent Ovarian, Fallopian Tube, and Primary Peritoneal Cancer [NCT01570582]Phase 2314 participants (Anticipated)Interventional2010-03-31Active, not recruiting
Phase Ib / II Study of BAY 1000394 in Combination With Cisplatin / Etoposide or Carboplatin / Etoposide as First-line Therapy in Subjects With Extensive Disease Small Cell Lung Cancer [NCT01573338]Phase 1/Phase 243 participants (Actual)Interventional2013-02-25Terminated
A Phase II Study of Non-Small Cell Cancer of the Lung Utilizing Low-Dose Weekly Therapy of Taxotere and Carboplatin [NCT00003562]Phase 238 participants (Anticipated)Interventional1998-07-31Active, not recruiting
Phase I Study of Romidepsin (ISTODAX®) Plus ICE for Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma [NCT01590732]Phase 122 participants (Actual)Interventional2012-10-29Completed
Almonertinib Vs. Erlotinib/Chemotherapy for Neo-adjuVant Treatment of Stage IIIA-N2 EGFR-mutated NSCLC: a Multicenter, Open-label, Phase II Randomized Controlled Trial [NCT04455594]Phase 2168 participants (Anticipated)Interventional2020-10-31Not yet recruiting
A Phase I Dose Escalation Study of Capecitabine, Carboplatin and Weekly Paclitaxel and a Phase II Trial of the Same Combination in Patients With Adenocarcinoma of Unknown Primary [NCT00201734]Phase 1/Phase 257 participants (Actual)Interventional2005-06-30Terminated(stopped due to Due to lack of funding provided for Phase II portion of trial)
Phase II Study of Pembrolizumab and Bevacizumab in Combination With Platinum-based Chemotherapy Followed by Pembrolizumab, Bevacizumab and Olaparib in Patients With Platinum-sensitive Recurrent Ovarian Cancer [NCT05158062]Phase 235 participants (Anticipated)Interventional2022-04-20Recruiting
Phase Ib, Multicenter, Open Label Study of PDR001 in Combination With Platinum Doublet Chemotherapy and Other Immunooncology Agents in PD-L1 Unselected, Metastatic NSCLS Patients (ElevatION:NSCLC-101 Trial) [NCT03064854]Phase 1111 participants (Actual)Interventional2017-05-24Terminated(stopped due to Recruitment halted prematurely due to competitive landscape for lung cancer therapies)
A Randomized Open-Label Phase II Trial of Pemetrexed and a Platinum (Carboplatin or Cisplatin) With or Without Erlotinib in Patients With Non-Small Cell Lung Cancer Harboring Activating Epidermal Growth Factor Receptor Mutations and Acquired Resistance to [NCT01928160]Phase 20 participants (Actual)Interventional2014-06-30Withdrawn(stopped due to study not accruing)
A Phase I Trial of Pegylated Liposomal Doxorubicin (PLD), Carboplatin and NCI Supplied Veliparib (ABT-888), and NCI Supplied Bevacizumab in Recurrent Platinum Sensitive Ovarian, Primary Peritoneal and Fallopian Tube Cancer [NCT01459380]Phase 141 participants (Actual)Interventional2011-10-11Completed
Neoadjuvant Biweekly Doxorubicin and Cyclophosphamide With GMCSF Followed by Weekly Carboplatin/Nab-paclitaxel Plus or Minus Trastuzumab and Plus or Minus Bevacizumab in Treatment of Large or Inflammatory Breast Cancer-a Phase II Study [NCT00254592]Phase 243 participants (Actual)Interventional2005-10-31Completed
A Randomized, Phase III Comparison of Gemcitabine/Irinotecan Followed by IRESSA Versus Paclitaxel/Carboplatin/Etoposide Followed by IRESSA in the First-Line Treatment of Patients With Carcinoma of Unknown Primary Site [NCT00193596]Phase 3198 participants (Actual)Interventional2003-09-30Completed
Phase I/II Study of PS-341 in Combination With Paclitaxel, Carboplatin, and Concurrent Thoracic Radiation Therapy for Non-small Cell Lung Cancer (NSCLC) [NCT00093756]Phase 1/Phase 252 participants (Actual)Interventional2004-09-30Completed
A Phase II Study of Gemcitabine/Carboplatin/Bevacizumab in Platinum Sensitive Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Patients. [NCT00267696]Phase 245 participants (Actual)Interventional2005-11-30Completed
Phase II Trial of Induction Gemcitabine and Carboplatin Followed by Paclitaxel and Carboplatin With Concurrent Thoracic Radiation for Patients With Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer [NCT00226590]Phase 239 participants (Actual)Interventional2003-04-30Completed
Lucentis in the Treatment of Retinoblastoma - A Phase II, Single Center, Randomized Study to Evaluate the Efficacy of Ranibizumab in Subjects With Retinoblastoma [NCT01899066]Phase 220 participants (Anticipated)Interventional2013-07-31Recruiting
A Randomized Phase II Study of Preoperative Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in Early Stage, HER-2 Positive Breast Cancer [NCT00148668]Phase 281 participants (Actual)Interventional2003-12-31Completed
A Phase II Study of Paclitaxel/Carboplatin Plus Bevacizumab/Erlotinib in the First Line Treatment of Patients With Carcinoma of Unknown Primary Site [NCT00360360]Phase 260 participants (Actual)Interventional2006-07-31Completed
A Phase II, Randomized Study of Cytoreductive Surgery Combined With Niraparib Maintenance in Platinum-sensitive, Secondary Recurrent Ovarian Cancer [NCT03983226]Phase 2167 participants (Anticipated)Interventional2019-10-18Recruiting
A Clinical Study of the Efficacy and Safety of Chidamide in Combination With Camrelizumab and Carboplatin or Capecitabine in the Second and Third Line Treatment of Relapsed/Metastatic Triple-negative Breast Cancer [NCT05438706]Phase 270 participants (Anticipated)Interventional2022-07-10Not yet recruiting
An Open Label, Randomized Phase I/II Trial of Carboplatin Plus Etoposide With ot Without MPDL3280A in Untreated Extensive Stage Small Cell Lung Cancer [NCT02748889]Phase 1/Phase 21 participants (Actual)Interventional2016-03-31Terminated(stopped due to Difficulties with recruitment)
A Phase 1b/2 Study of OMP-59R5 in Combination With Etoposide and Platinum Therapy in Subjects With Untreated Extensive Stage Small Cell Lung Cancer (PINNACLE) [NCT01859741]Phase 1/Phase 2172 participants (Actual)Interventional2012-01-07Terminated(stopped due to OMP-59R5 did not improve PFS.)
Carboplatin-gemcitabine Versus Cisplatin-gemcitabine as Neoadjuvant Chemotherapy for Treatment of Muscle Invasive Urinary Bladder Cancer: a Prospective Randomized Trial [NCT05822934]Phase 320 participants (Anticipated)Interventional2022-11-01Recruiting
A Phase III, Randomized, Open-Label Study of Pralsetinib Versus Standard of Care for First-Line Treatment of RET Fusion-Positive, Metastatic Non-Small Cell Lung Cancer [NCT04222972]Phase 3226 participants (Anticipated)Interventional2020-07-24Recruiting
REACTION: A Phase II Study of Etoposide and Cis/Carboplatin With or Without Pembrolizumab in Untreated Extensive Small Cell Lung Cancer [NCT02580994]Phase 2125 participants (Actual)Interventional2017-12-08Completed
Phase IB-II, Open Label, Multicenter Feasibility Study of Pazopanib in Combination With Paclitaxel and Carboplatin in Patients With Platinum-Refractory/Resistant Ovarian, Fallopian Tube or Peritoneal Carcinoma [NCT01402271]Phase 1/Phase 288 participants (Anticipated)Interventional2012-07-31Completed
Treatment Protocol for Relapsed Anaplastic Large Cell Lymphoma of Childhood and Adolescence [NCT00317408]96 participants (Anticipated)Interventional2004-04-30Active, not recruiting
Phase II Trial Investigating Tailoring First-Line Therapy For Advanced Stage Diffuse Large B-Cell Non-Hodgkin's Lymphoma Based on Mid-Treatment Positron Emission Tomography (PET) Scan Results [NCT00324467]Phase 2150 participants (Actual)Interventional2006-08-31Active, not recruiting
Bevacizumab and Erlotinib First-Line Therapy in Advanced Non-Squamous Non-Small-Cell Lung Cancer (Stage IIIB/IV) Followed by Platinum-Based Chemotherapy at Disease Progression. A Multicenter Phase II Trial [NCT00354549]Phase 2104 participants (Actual)Interventional2006-01-31Completed
A Multicenter Phase II Trial of Pemetrexed Plus Carboplatin With or Without Apatinib in Patients With Advanced Non-small Cell Lung Cancer Without EGFR Mutation, ALK Gene Rearrangement, and ROS1 Gene Rearrangement [NCT03164694]Phase 2128 participants (Anticipated)Interventional2017-05-20Recruiting
Neoadjuvant Docetaxel + Carboplatin Versus Epirubicin+Cyclophosphamide Followed by Docetaxel in Triple-Negative, Early-Stage Breast Cancer (NeoCART): Study Protocol for a Multicenter, Randomized Controlled, Open-Label, Phase 2 Trial [NCT03154749]Phase 293 participants (Actual)Interventional2016-09-01Completed
Pilot Study of Standard Therapy for Prevention of Nausea and Emesis Associated With First Line Post-Operative Intraperitoneal Chemotherapy [NCT01275664]4 participants (Actual)Interventional2011-06-30Terminated(stopped due to Study terminated due to no patient population available)
A Randomized, Controlled, Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Sheng Bai Oral Liquid in Prevention and Treatment for The Decrease of Neutrophils After Chemotherapy in Patients With Non-Small-Cell Lung Cancer [NCT03413358]240 participants (Anticipated)Interventional2018-01-15Recruiting
A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF- 06439535 PLUS PACLITAXEL-CARBOPLATIN AND BEVACIZUMAB PLUS PACLITAXEL -CARBOPLATIN FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH ADVANCED NON-SQUAMOUS NON-SMALL CELL LUNG CANCER. [NCT02364999]Phase 3719 participants (Actual)Interventional2015-04-30Completed
A Phase Ib Safety Run-in and Randomized Phase II, Open-label Study to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of M6620 in Combination With Avelumab and Carboplatin in Comparison to Standard of Care Therapy in Participants With PA [NCT03704467]Phase 13 participants (Actual)Interventional2019-03-04Completed
A PHASE I TRIAL OF HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS BONE MARROW AND PERIPHERAL BLOOD PROGENITOR CELL RESCUE IN PATIENTS WITH PLATINUM-SENSITIVE, CHEMOTHERAPY-RESPONSIVE EPITHELIAL OVARIAN CARCINOMA [NCT00002600]Phase 123 participants (Actual)Interventional1994-10-21Completed
Neoadjuvant Inetetamab Combined With Pertuzumab and Paclitaxel/Carboplatin for Locally Advanced HER2-Positive Breast Cancer: a Prospective, Single-arm, Multi-center Phase II Study [NCT05749016]Phase 230 participants (Anticipated)Interventional2021-11-01Recruiting
INFUSION OF ACTIVATED T CELLS AND LOW DOSE INTERLEUKIN 2 COMBINED WITH PERIPHERAL BLOOD STEM CELL TRANSPLANTATION FOR THE TREATMENT OF WOMEN WITH METASTATIC BREAST CANCER: PHASE I/II [NCT00002780]Phase 1/Phase 260 participants (Anticipated)Interventional1996-05-31Active, not recruiting
A Phase II Study of Pemetrexed/Carboplatin/Radiotherapy and Bevacizumab in Patients With Unresectable Stage III Non-Small-Cell Lung Cancer [NCT00402883]Phase 25 participants (Actual)Interventional2006-11-30Terminated(stopped due to Terminated due to bevacizumab and chemoradiotherapy toxicity)
(NJ 1508) Modulation of Autophagy With Hydroxychloroquine in Combination With Carboplatin, Paclitaxel and Bevacizumab in Patients With Advanced/Recurrent Non-Small Cell Lung Cancer - A Phase I/II Study [NCT00728845]Phase 1/Phase 28 participants (Actual)Interventional2008-06-16Terminated(stopped due to Slow accrual)
A RANDOMISED TRIAL OF PACLITAXEL (TAXOL) IN COMBINATION WITH PLATINUM CHEMOTHERAPY VS. CONVENTIONAL PLATINUM-BASED CHEMOTHERAPY IN THE TREATMENT OF WOMEN WITH RELAPSED OVARIAN CANCER [NCT00002894]Phase 3800 participants (Anticipated)Interventional1996-03-31Completed
Carboplatin in the Adjuvant Treatment of Stage I Seminoma: A Radomized Comparison of Single Agent Carboplatin With Radiotherapy in the Adjuvant Treatment of Stage I Seminoma of the Testis, Following Orchidectomy [NCT00003014]Phase 3800 participants (Anticipated)Interventional1998-04-30Completed
Phase I/II Study of Samarium 153 as Part of a Double (Sequential) Autologous Bone Marrow Transplant (ABMT) for Patients With Stage IV Breast Cancer [NCT00003086]Phase 1/Phase 212 participants (Anticipated)Interventional1997-03-31Terminated(stopped due to no participants enrolled in a three year period)
HIGH-DOSE CHEMOTHERAPY WITH CYCLOPHOSPHAMIDE, ETOPOSIDE, AND CARBOPLATIN FOLLOWED BY RESCUE WITH AUTOLOGOUS BONE MARROW AND AUTOLOGOUS PERIPHERAL BLOOD STEM CELLS IN PATIENTS WITH POOR PROGNOSIS BREAST CANCER [NCT00002509]Phase 1/Phase 20 participants Interventional1991-11-30Completed
Myeloablative Chemotherapy With Bone Marrow Rescue For Rare Poor-Prognosis Cancers [NCT00002515]Phase 20 participants Interventional1992-10-31Completed
Neoadjuvant Therapy of Sintilimab Combined With Chemotherapy for Resectable Squamous Cell NSCLC（neoSCORE Ⅱ）：A Prospective, Randomized, Open-Label, Multi-Center Phase 3 Trial [NCT05429463]Phase 3250 participants (Anticipated)Interventional2022-11-11Recruiting
Multiple Cycles of High Dose Chemotherapy Supported With Filgrastim and Peripheral Blood Progenitor Cells in Patients With Metastatic Breast Cancer [NCT00003392]Phase 261 participants (Actual)Interventional1997-09-30Completed
A Phase II Trial of Concurrent Carboplatin/VP-16 and Radiation Followed by Paclitaxel (Taxol) for Poor-Risk Stage III Non-Small Cell Lung Cancer [NCT00003158]Phase 296 participants (Actual)Interventional1998-02-28Completed
A PHASE III STUDY OF ADJUVANT CHEMOTHERAPY AFTER RESECTION FOR PATIENTS WITH T2N0 STAGE I NON-SMALL CELL CARCINOMA OF THE LUNG [NCT00002852]Phase 3500 participants (Actual)Interventional1996-10-31Completed
A Phase I Study of Thiotepa in Combination With Carboplatin and Topotecan With Peripheral Blood Progenitor Cell Support for the Treatment of Children With Recurrent or Refractory Solid Tumors. [NCT00003194]Phase 124 participants (Anticipated)Interventional1997-07-31Terminated(stopped due to Study enrollment did not meet expected goals)
A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-022, an Anti-TIM-3 Monoclonal Antibody, in Patients With Advanced Solid Tumors (AMBER) [NCT02817633]Phase 1475 participants (Anticipated)Interventional2016-07-08Recruiting
A Phase II Trial Using Multiple Cycles of High Dose Sequential Carboplatin, Paclitaxel and Topotecan With Peripheral Blood Stem Cell (PBSC) Support as Initial Chemotherapy in Patients With Suboptimally Debulked Stage III or IV Ovarian, Fallopian Tube or P [NCT00003944]Phase 23 participants (Actual)Interventional1998-08-31Completed
RANDOMIZED TRIAL OF SURGERY VERSUS RADIOTHERAPY IN PATIENTS WITH STAGE IIIa NON-SMALL CELL LUNG CANCER AFTER A RESPONSE TO INDUCTION-CHEMOTHERAPY [NCT00002623]Phase 3640 participants (Anticipated)Interventional1994-12-31Completed
A Randomized, Prospective Phase III Comparison of Paclitaxel-Carboplatin Versus Docetaxel-Carboplatin as First Line Chemotherapy in Stage Ic-IV Epithelial Ovarian Cancer [NCT00003998]Phase 31,050 participants (Anticipated)Interventional1998-10-31Completed
Tandem Autologous Peripheral Blood Stem Cell Transplantation (PBSCT) After High Dose Paclitaxel Followed by Ifosfamide, Carboplatin, and Etoposide (ICE) for the Treatment of Lung Cancer [NCT00003284]Phase 230 participants (Anticipated)Interventional1998-01-31Active, not recruiting
A Phase II Study of Docetaxel and Carboplatin for Suboptimally Debulked Stage III or Stage IV Ovarian and Fallopian Tube Carcinoma [NCT00003560]Phase 240 participants (Anticipated)Interventional1998-05-31Active, not recruiting
A Phase I Study of Docetaxel (Taxotere), Carboplatin, and Gemcitabine (DoCaGem) as First-Line Therapy for Patients With High-Risk Epithelial Tumors of Mullerian Origin [NCT00004082]Phase 10 participants Interventional1999-07-31Completed
A Phase II Study of Induction Chemotherapy Followed by Concomitant Paclitaxel (1 Hour Infusion), Fluorouracil, Hydroxyurea and Hyperfractionated Radiotherapy for Advanced Oral, Pharynx and Larynx Cancer [NCT00004094]Phase 20 participants Interventional1999-08-31Active, not recruiting
PHASE II STUDY OF CARBOPLATIN (CBDCA) IN THE TREATMENT OF CHILDREN AND ADULTS WITH PROGRESSIVE LOW GRADE GLIOMAS [NCT00002749]Phase 225 participants (Anticipated)Interventional1993-02-28Completed
Treatment of Ovarian Carcinoma With DNP-Modified Autologous Tumor Vaccine [NCT00003386]Phase 20 participants Interventional1999-07-31Terminated
A Phase II Study of Induction Chemotherapy With Paclitaxel and Carboplatin Followed by Radiation Therapy With RSR13 for Locally Advanced Inoperable Non-Small Cell Lung Cancer [NCT00004202]Phase 20 participants Interventional1998-10-31Completed
A Randomized Trial of Paclitaxel/Epirubicin/Carboplatin Combination (TEC) Versus Paclitaxel/Carboplatin (TC) in the Treatment of Women With Advanced Ovarian Cancer [NCT00004934]Phase 30 participants Interventional1999-08-31Completed
Topotecan/Paclitaxel Induction Followed by Consolidation Chemoradiotherapy for Limited Stage Small Cell Lung Cancer: A Phase II Study [NCT00003812]Phase 275 participants (Actual)Interventional1999-03-31Completed
A Double-blind, Multicenter, Parallel Study Comparing the Efficacy and Safety of Kytril Tablets With Placebo, in the Prevention of Nausea and Vomiting During the Days Following Administration of IV Cyclophosphamide-based or Carboplatin-based Chemotherapy [NCT00005024]Phase 30 participants InterventionalActive, not recruiting
Intensive Chemotherapy With Peripheral Blood Stem Cell Support for Small Cell Lung Cancer [NCT00003860]Phase 236 participants (Anticipated)Interventional1998-09-30Completed
Evaluation of the Combination of Docetaxel (Taxotere)/ Carboplatin in Patients With Metastatic or Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT00003908]Phase 268 participants (Actual)Interventional1999-11-30Completed
Phase I Dose Escalation Study of Tirapazamine (NSC 130181) in Combination With Carboplatin and Paclitaxel in Advanced Malignant Solid Tumors [NCT00005078]Phase 144 participants (Actual)Interventional2000-03-31Completed
A Single-Arm, Multicenter, Open-Label, Phase 2 Study of Nab®-Paclitaxel (Abraxane®) and Carboplatin Chemotherapy Plus Necitumumab (LY3012211) in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC) [NCT02392507]Phase 254 participants (Actual)Interventional2015-10-12Completed
A Phase I/II Study of Intensive-Dose Etoposide, Topotecan and Carboplatin (ETC) Followed by Autologous Stem Cell Rescue in Chemosensitive Ovarian Cancer Patients With Either Minimal Residual Disease or at First Relapse [NCT00005612]Phase 1/Phase 23 participants (Actual)Interventional1999-08-31Terminated(stopped due to Low accrual)
A Phase II Study of Cyclophosphamide, Thiotepa, and Carboplatin (CTC) as a Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation in Patients With Breast Cancer [NCT00005798]Phase 2209 participants (Actual)Interventional1995-07-31Completed
A Phase II Study of Estramustine, Docetaxel, and Carboplatin With G-CSF Support in Men With Hormone Refractory Prostate Cancer [NCT00005810]Phase 240 participants (Actual)Interventional2000-03-31Completed
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Compare the Efficacy and Safety of Neoadjuvant Treatment With Tislelizumab (BGB-A317, Anti-PD-1 Antibody) or Placebo Plus Platinum-Based Doublet Chemotherapy Followed By Adjuvant Tislelizuma [NCT04379635]Phase 3453 participants (Actual)Interventional2020-05-29Active, not recruiting
High Dose Combined Modality Therapy With Peripheral Blood Progenitor Cell Transplantation as Primary Treatment for Patients With Mantle Cell Lymphoma [NCT00003541]Phase 1/Phase 224 participants (Anticipated)Interventional1998-06-30Completed
A Phase II Trial of High Dose Paclitaxel, Carboplatin and Topotecan With Peripheral Blood Stem Cell Support in Extensive Stage Small Cell Cancer [NCT00003943]Phase 23 participants (Actual)Interventional1998-09-30Completed
Phase II Trial of Paclitaxel and Carboplatin With Amifostine in Advanced Recurrent or Refractory Endometrial Adenocarcinoma [NCT00003127]Phase 257 participants (Actual)Interventional1998-02-28Completed
A Phase II Study of Sequential Carboplatin, Paclitaxel and Hycamtin in Patients With Previously Untreated Advanced Ovarian Cancer [NCT00003733]Phase 240 participants (Anticipated)Interventional1997-12-31Active, not recruiting
A Randomized Phase II Trial of Cisplatin or Carboplatin With Gemcitabine in Patients With Advanced Non-Small Cell Lung Cancer [NCT00004201]Phase 20 participants InterventionalCompleted
Trial of Chemotherapy Utilizing Carboplatin, Vincristine, Cyclophosphamide and Etoposide for the Treatment of Central Nervous System Primitive Neurectodermal Tumors of Childhood [NCT00003859]Phase 3230 participants (Anticipated)Interventional1992-04-30Completed
A Phase I/II Study in Metastatic Breast Cancer Patients Infused With Stromagen and Isolated, Mobilized, Autologous Peripheral Blood CD34+ Progenitor Cells After High-Dose Chemotherapy [NCT00003877]Phase 1/Phase 230 participants (Anticipated)Interventional1998-09-30Completed
A Phase III Multicenter, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Nab-Paclitaxel for Chemotherapy-Naive Patients With Stage IV Non-Squamous Non-Small C [NCT02367781]Phase 3723 participants (Actual)Interventional2015-04-16Completed
A Phase III Randomized Study of Amifostine Mucosal Protection for Patients With Favorable Performance Inoperable Stage II-III A/B Non-Small Cell Lung Cancer (NSCLC) Receiving Sequential Induction and Concurrent Hyperfractionated Radiotherapy With Paclitax [NCT00003313]Phase 3243 participants (Actual)Interventional1998-09-30Completed
A Randomized Phase III Trial of Sequential High Dose Chemotherapy or Standard Chemotherapy for Optimally Debulked FIGO Stage III and IV Ovarian Cancer [NCT00004921]Phase 30 participants Interventional1998-09-30Completed
A Phase I Study of Paclitaxel, Carboplatin, and Increasing Doses of Doxil in Untreated Ovarian, Peritoneal, and Tubal Carcinoma [NCT00003385]Phase 148 participants (Anticipated)Interventional1999-03-31Completed
A Phase II Study of Carboplatin and Paclitaxel in Elderly Patients With Metastatic or Recurrent Unresectable Non-Small Cell Lung Cancer [NCT00005059]Phase 251 participants (Actual)Interventional2000-01-31Completed
A Phase I Study of Induction Carboplatin / Paclitaxel Chemotherapy, Pre-operative Radiotherapy With Gadolinium Texaphyrin (Gd-Tex), and Surgical Resection in Stage IIIA (N2) Non-small Cell Lung Carcinoma. [NCT00005065]Phase 112 participants (Anticipated)Interventional2000-01-31Completed
Phase I Study of Fludarabine, Carboplatin, and Topotecan for Patients With Relapsed/Refractory Acute Leukemia and Advanced Myelodysplastic Syndromes [NCT00005593]Phase 131 participants (Actual)Interventional1998-09-30Completed
A Phase 1 Study to Evaluate the Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Patients With Advanced Solid Tumors [NCT02122770]Phase 151 participants (Actual)Interventional2014-04-01Completed
A Phase III, Open-Label, Randomized Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Carboplatin+Paclitaxel With or Without Bevacizumab Compared With Carboplatin + Paclitaxel + Bevacizumab in Chemotherapy-Naïve Patients With Stag [NCT02366143]Phase 31,202 participants (Actual)Interventional2015-03-31Completed
Pilot Study of Tislelizumab (BGB-A317) in Recurrent Mismatch Repair Deficient Endometrial Cancer and the Effect on the Tumor Microenvironment [NCT04906382]Early Phase 12 participants (Actual)Interventional2021-07-01Terminated(stopped due to Sponsor reorganization)
Platinum-Gemcitabine-Avastin (PGA) for Platinum-resistant/Refractory, Paclitaxel-Pretreated Recurrent Ovarian and Peritoneal Carcinoma [NCT01936974]Phase 27 participants (Actual)Interventional2013-09-30Terminated(stopped due to PI Decision)
A Phase II Study of AZD1775 Plus Pemetrexed and Carboplatin Followed by a Randomised Comparison of Pemetrexed and Carboplatin With or Without AZD1775 in Patients With Previously Untreated Stage IV Non-Squamous Non-Small-Cell Lung Cancer [NCT02087241]Phase 222 participants (Actual)Interventional2014-03-31Terminated(stopped due to The sponsor decided to terminate the study.)
A Phase 1 Dose Escalation and Phase 2 Randomized, Placebo-Controlled Study of the Efficacy and Tolerability of Veliparib in Combination With Paclitaxel/Carboplatin-Based Chemoradiotherapy Followed by Veliparib and Paclitaxel/Carboplatin Consolidation in S [NCT02412371]Phase 1/Phase 248 participants (Actual)Interventional2015-04-30Terminated(stopped due to Phase 2 was not conducted due to a change in the standard of care for newly diagnosed, unresectable Stage III NSCLC)
A Protocol For Nonmetastatic Rhabdomyosarcoma [RMS-2005] [NCT00379457]Phase 3600 participants (Anticipated)Interventional2006-06-30Recruiting
NYU 05-40 PBMTC ONC-032P:High Dose Temozolomide,Thiotepa and Carboplatin With Autologous Stem Cell Rescue (ASCR) Followed by Continuation Therapy With 13-cis-retinoic Acid in Patients With Recurrent/Refractory Malignant Brain Tumors [NCT00528437]Phase 246 participants (Actual)Interventional2005-10-31Completed
Phase III Randomized Study of Adjuvant Therapy With a Platinum-Containing Regimen (e.g., CBDCA or CAP: CTX/DOX/CDDP) vs No Adjuvant Therapy in Patients With Fully Resected Early Stage Ovarian Cancer [NCT00002477]Phase 30 participants Interventional1991-04-30Active, not recruiting
PROTOCOL FOR THE TREATMENT OF MALIGNANT NON-TESTICULAR GERM CELL TUMORS [NCT00002489]Phase 20 participants Interventional1991-10-31Completed
PHASE I/II TRIAL OF THE ADDITION OF TAXOL TO HIGH DOSE CARBOPLATIN AND CYCLOPHOSPHAMIDE WITH AUTOLOGOUS PERIPHERAL BLOOD PROGENITOR CELL SUPPORT IN PATIENTS WITH HIGH RISK STAGE II AND III BREAST CANCER [NCT00002627]Phase 1/Phase 230 participants (Anticipated)Interventional1994-11-30Active, not recruiting
A TRIAL OF ADJUVANT CHEMOTHERAPY IN PATIENTS WITH INTRAOCULAR RETINOBLASTOMA [NCT00002675]Phase 250 participants (Anticipated)Interventional1995-05-31Completed
PHASE I STUDY OF CONTINUOUS INFUSION CARBOPLATIN AND TOPOTECAN IN THE TREATMENT OF RELAPSED ACUTE LEUKEMIA AND BLAST CRISIS CHRONIC MYELOGENOUS LEUKEMIA [NCT00002693]Phase 10 participants Interventional1995-10-31Completed
A Randomized, Open-label Study of the Effect of Omnitarg in Combination With Carboplatin-based Chemotherapy Versus Carboplatin-based Therapy Alone on Treatment Response in Patients With Platinum-sensitive Recurrent Ovarian Cancer [NCT02004093]Phase 2149 participants (Actual)Interventional2005-12-31Completed
ToPCourT: A Phase II Trial of Trilaciclib, Pembrolizumab, Gemcitabine and Carboplatin in Locally Advanced Unresectable or Metastatic Triple-Negative Breast Cancer (TNBC) [NCT06027268]Phase 236 participants (Anticipated)Interventional2023-12-31Not yet recruiting
A Randomized, Open Label, Parallel Controlled, Multicenter Phase II Clinical Study of Carelizumab Combined With TCb (Docetaxel+Carboplatin) Versus TCb Neoadjuvant Therapy for Triple Negative Breast Cancer [NCT05475678]Phase 2369 participants (Anticipated)Interventional2022-12-20Recruiting
A Phase II, Open-label, Multicentre, Randomised Study of Neoadjuvant and Adjuvant Treatment in Patients With Resectable, Early-stage (II to IIIB) Non-small Cell Lung Cancer (NeoCOAST-2) [NCT05061550]Phase 2350 participants (Anticipated)Interventional2022-04-14Recruiting
A Phase II Study of Chemo-Immunotherapy Followed by Durvalumab (MEDI4736) and Ceralasertib (AZD6738) in Treatment Naïve Patients With Extensive Stage Small Cell Lung Cancer (ES-SCLC) Big Ten Cancer Research Consortium BTCRC-LUN18-363 [NCT04699838]Phase 230 participants (Anticipated)Interventional2021-04-20Recruiting
High Dose Carboplatin, Etoposide, Cyclophosphamide and Autologous Bone Marrow Transplantation for Relapsed and Refractory Germ Cell Cancer: A Phase II Pilot Study [NCT00002943]Phase 211 participants (Actual)Interventional1993-02-28Completed
Ultimate Low Grade Glioma Study [NCT00003015]Phase 3200 participants (Anticipated)Interventional1997-01-31Active, not recruiting
A Phase III Randomized Controlled Clinical Trial of Carboplatin and Paclitaxel (or Gemcitabine) Alone or in Combination With Bevacizumab (NSC #704865) Followed by Bevacizumab and Secondary Cytoreductive Surgery in Platinum-Sensitive, Recurrent Ovarian, Pe [NCT00565851]Phase 31,052 participants (Actual)Interventional2007-12-06Active, not recruiting
Treatment for Infants and Children With Intermediate Risk Neuroblastoma: A Phase III Intergroup CCG/POG Study [NCT00003093]Phase 3573 participants (Actual)Interventional1988-03-31Completed
Phase II Clinical and Laboratory Study of Irinotecan/Cisplatin Chemotherapy Followed by Surgery in Stage III NSCLC [NCT00003111]Phase 210 participants (Actual)Interventional1997-04-30Completed
A Pilot Study of Intensive Chemotherapy With Peripheral Stem Cell Support for Infants With Malignant Brain Tumors [NCT00003141]Phase 194 participants (Actual)Interventional1998-03-31Completed
Phase II Study of Gemcitabine, Carboplatin, and Panitumumab (GCaP) as Neoadjuvant Chemotherapy in Patients With Muscle-Invasive Bladder Cancer [NCT01916109]Phase 24 participants (Actual)Interventional2013-08-31Terminated(stopped due to Lack of accrual)
An Open-Label, Randomized, Phase 3 Trial of Nivolumab Versus Investigator's Choice Chemotherapy as First-Line Therapy for Stage IV or Recurrent PD-L1+ Non-Small Cell Lung Cancer [NCT02041533]Phase 3541 participants (Actual)Interventional2014-03-27Completed
A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate QL1706 Plus Paclitaxel-Cisplatin/Carboplatin With or Without Bevacizumab for the First-Line Treatment of Persistent, Recurrent or Metastatic Cervical Cancer [NCT05446883]Phase 3498 participants (Anticipated)Interventional2022-09-23Recruiting
A Phase 1 Dose Escalation and Phase 2 Randomized Double-Blind Study of Veliparib in Combination With Carboplatin and Etoposide as a Therapy of Treatment-Naïve Extensive Stage Disease Small Cell Lung Cancer [NCT02289690]Phase 1/Phase 2221 participants (Actual)Interventional2014-10-13Completed
A Phase II, Single Arm, Open-Label, Multicenter, Safety and Tolerability Trial With Nab-Paclitaxel (ABRAXANE®) Plus Carboplatin Followed by Nab-Paclitaxel Monotherapy as First-Line Treatment for Subjects With Locally Advanced or Metastatic Nonsmall Cell L [NCT02289456]Phase 240 participants (Actual)Interventional2015-04-28Completed
Efficacy of Primary Debulking Surgery Versus Neoadjuvant Chemotherapy in Stage IV Ovarian Cancer: a Phase III Randomized Controlled Study [NCT05371301]Phase 3200 participants (Anticipated)Interventional2021-07-16Recruiting
A Feasibility Study Investigating Translational Science in Chemotherapy-Naive Patients With Stage IIIb or IV Non-Small Cell Lung Cancer (NSCLC) Treated With the EGFR-TKI, Erlotinib [NCT00550537]Phase 2116 participants (Actual)Interventional2007-10-31Completed
A Safety and Feasibility Study of Bevacizumab With Paclitaxel, Carboplatin and Chest Radiotherapy in Patients With Locally Advanced Non-Small Lung Cancer [NCT00369551]Phase 136 participants (Actual)Interventional2006-06-30Terminated
A Phase 1b, Open-Label Study to Assess the Antitumor Activity of Neoadjuvant Chemotherapy With or Without BINTRAFUSP ALFA in Patients With Metastatic Advanced Stage Ovarian Cancer [NCT05145569]Phase 133 participants (Anticipated)Interventional2022-09-30Not yet recruiting
A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate AK104 Plus Platinum-containing Chemotherapy With or Without Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer [NCT04982237]Phase 3440 participants (Anticipated)Interventional2021-08-27Recruiting
A Phase 1b, Multicenter, Open-label, Dose Finding Study to Assess the Safety, Tolerability, and Preliminary Efficacy of CC-90011 Given in Combination With Cisplatin and Etoposide in First Line, Extensive Stage Subjects With Small Cell Lung Cancer [NCT03850067]Phase 190 participants (Anticipated)Interventional2019-03-12Active, not recruiting
Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment [NCT02035345]Phase 415 participants (Actual)Interventional2014-01-31Terminated(stopped due to Extended Carboplatin Infusion did not Reduce Frequency of Hypersensitivity Reactions)
A Randomized Phase II/III Study of Paclitaxel/Carboplatin/Metformin (NSC#91485) Versus Paclitaxel/Carboplatin/Placebo as Initial Therapy for Measurable Stage III or IVA, Stage IVB, or Recurrent Endometrial Cancer [NCT02065687]Phase 2/Phase 3469 participants (Actual)Interventional2014-03-17Active, not recruiting
A Phase IIa, Single-arm, Multicenter Study to Investigate the Clinical Activity and Safety of Avelumab in Combination With Cetuximab Plus Gemcitabine and Cisplatin in Participants With Advanced Squamous NSCLC [NCT03717155]Phase 243 participants (Actual)Interventional2018-10-30Completed
Induction Treatment in Patients With Squamous Cell Carcinoma (SCC) of the Head and Neck Region Consisting Concomitant Chemotherapy and Low-dose Ionizing Radiotherapy [NCT05992610]40 participants (Anticipated)Interventional2022-02-17Recruiting
A Randomized, Three-Arm, Open-Label Phase 3b Clinical Trial of Aumolertinib, Versus Aumolertinib With Chemotherapy, Versus Osimertinib for Patients With Metastatic NSCLC and an EGFR Mutation (TREBLE) [NCT05493501]Phase 38 participants (Actual)Interventional2022-12-14Terminated(stopped due to The study is being closed based on corporate changes at EQRx and is not related to any efficacy or safety issues with aumolertinib.)
Phase II Investigation of Use of CNS Active Pembrolizumab and Chemotherapy for Asymptomatic Brain Metastasis From Non-small Cell Lung Cancer (NSCLC) [NCT04964960]Phase 245 participants (Anticipated)Interventional2022-05-19Recruiting
Randomized Phase II Trial of Gemcitabine, Avelumab and Carboplatin vs. No Neoadjuvant Therapy Preceding Surgery for Cisplatin-Ineligible Muscle-Invasive Urothelial Carcinoma: SWOG GAP TRIAL [NCT04871529]Phase 2196 participants (Anticipated)Interventional2022-08-10Suspended(stopped due to undergoing nrevision)
A Phase 3, Randomized, Double-blind, Multicenter Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer (RUBY) [NCT03981796]Phase 3787 participants (Actual)Interventional2019-07-18Active, not recruiting
A Phase II Study With a Limited Safety Lead-In of Enzalutamide in Combination With Carboplatin and Paclitaxel in Advanced Stage or Recurrent Endometrioid Endometrial Cancer [NCT02684227]Phase 253 participants (Actual)Interventional2016-08-24Completed
A Randomized Phase III Trial of Adjuvant Therapy Comparing Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel With or Without Carboplatin for Node-Positive or High-Risk Node-Negative Triple-Negative Invasive Breast Cancer [NCT02488967]Phase 3782 participants (Anticipated)Interventional2015-07-26Recruiting
Randomized Trial of Surgical Resection With or Without Pre-Operative Chemotherapy in Patients With Operable Non-Small Cell Lung Cancer (NSCLC) of Any Stage [NCT00003159]Phase 3600 participants (Anticipated)Interventional1997-08-31Completed
Concurrent Carboplatin, Paclitaxel, and Radiation Therapy Versus Induction Carboplatin and Paclitaxel Followed by Concurrent Carboplatin, Paclitaxel and Radiation Therapy for Patients With Unresectable Stage III Non-Small Cell Lung Cancer: A Phase III Tri [NCT00003387]Phase 3366 participants (Actual)Interventional1998-07-31Completed
Phase II Study of Continuous Infusion Carboplatin and Topotecan in the Treamtment of Relapsed Acute Myelogenous Leukemia (AML) [NCT00003255]Phase 238 participants (Actual)Interventional1999-11-30Completed
A Randomized Phase II Trial of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Paclitaxel and Carboplatin in HIV-positive Women With Locally Advanced Cervical Cancer (LACC) [NCT03834571]Phase 20 participants (Actual)Interventional2022-05-31Withdrawn(stopped due to Not approved by CTEP)
A 2-Arm Phase 2 Double-Blind Randomized Study of Carboplatin, Pemetrexed Plus Placebo Versus Carboplatin, Pemetrexed Plus Truncated Demcizumab as First-Line Treatment in Subjects With Stage IV Non-Squamous Non-Small Cell Lung Cancer [NCT02259582]Phase 282 participants (Actual)Interventional2015-02-28Completed
A Randomized Controlled, Phase III Trial in HER2-positive Lymph Node Positive Early Breast Cancer to Compare the Efficacy and Safety of Epriubin Plus Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and Pertuzumab (EC-THP) Versus Docetaxel and Carb [NCT05883852]Phase 31,406 participants (Anticipated)Interventional2023-06-07Recruiting
Letrozole for Estrogen/Progesterone Receptor Positive Low-grade Serous Epithelial Ovarian Cancer: a Randomized Phase III Trial (LEPRE Trial) [NCT05601700]Phase 3132 participants (Anticipated)Interventional2022-09-22Recruiting
Phase 2 Multiple-Dose, Multiple-Arm, Parallel Assignment Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of XmAb®20717 Alone or in Combination With Chemotherapy or Targeted Therapies in Selected Subjects With Metastatic Castration-Res [NCT05005728]Phase 285 participants (Anticipated)Interventional2021-10-22Recruiting
Phase II Study to Evaluate the Efficacy of 12-month Neoadjuvant Chemotherapy in Terms of Disease-free Survival in Patients With Localized Digestive Neuroendocrine Carcinomas [NCT04268121]Phase 278 participants (Anticipated)Interventional2021-01-05Recruiting
A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase III Clinical Study on Toripalimab Combined With Platinum-Based Doublet Drug Chemotherapy for Resectable, Stage II-III, Non-Small Cell Lung Cancer [NCT04158440]Phase 3501 participants (Actual)Interventional2020-04-07Active, not recruiting
A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus Carboplatin Paclitaxel Plus Concurrent and Extended Bevacizumab in Chinese Women With Newly Diagnosed, Previously Untreated, Stage III or Stage IV Epithelial Ovarian, Fallopian Tube, or P [NCT03635489]Phase 3100 participants (Actual)Interventional2018-08-15Completed
A Phase 2 Trial of Pembrolizumab (MK-3475) in Combination With Platinum Doublet Chemotherapy and Radiotherapy for Participants With Unresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC) (KEYNOTE-799) [NCT03631784]Phase 2217 participants (Actual)Interventional2018-10-19Active, not recruiting
Phase II Randomized Trial of Transoral Surgical Resection Followed by Low-Dose or Standard-Dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer [NCT01898494]Phase 2519 participants (Actual)Interventional2014-01-22Active, not recruiting
A Phase III Multicentre Trial of Weekly Induction Chemotherapy Followed by Standard Chemoradiation Versus Standard Chemoradiation Alone in Patients With Locally Advanced Cervical Cancer [NCT01566240]Phase 3500 participants (Actual)Interventional2012-11-08Active, not recruiting
Response-Adapted Therapy for Aggressive Non-Hodgkin's Lymphomas Based on Early [18F] FDG-PET Scanning [NCT00274924]Phase 2100 participants (Actual)Interventional2006-09-26Completed
Phase II Study of PD-1 Inhibition With Cemiplimab in Locally Advanced Hormone Receptor (HR) Positive HER2 Negative or Triple-Negative Breast Cancer Patients Undergoing Standard Neoadjuvant Chemotherapy [NCT04243616]Phase 236 participants (Anticipated)Interventional2020-03-05Recruiting
A Phase II Trial of Doxil, Carboplatin and Bevacizumab in Triple Negative Previously Untreated Metastatic Breast Cancer [NCT00608972]Phase 231 participants (Actual)Interventional2008-05-16Completed
Dose Intensive Chemotherapy for Children Less Than Ten Years of Age Newly-Diagnosed With Malignant Brain Tumors: A Pilot Study of Two Alternative Intensive Induction Chemotherapy Regimens, Followed by Consolidation With Myeloablative Chemotherapy (Thiotep [NCT00003273]Phase 20 participants (Actual)Interventional1997-11-30Withdrawn
A Phase I Study of Thrombopoietin (rhTPO) Plus G-CSF in Children Receiving Ifosfamide, Carboplatin, and Etoposide (I.C.E.) Chemotherapy for Recurrent or Refractory Solid Tumors [NCT00003597]Phase 116 participants (Actual)Interventional1998-11-30Completed
A Randomized Phase III Comparative Study of Paclitaxel With Carboplatin Versus Mitomycin, Ifosfamide, Cisplatin (MIC) Chemotherapy in Inoperable Advanced Stage Non-Small Cell Lung Cancer [NCT00004887]Phase 30 participants Interventional1999-01-31Active, not recruiting
A Randomized Phase III Trial of Surgery Alone or Surgery Plus Preoperative Paclitaxel/Carboplatin in Clinical Stage IB (T2N0), II (T1-2N1, T3N0) and Selected IIIA (T3N1) Non-Small Cell Lung Cancer (NSCLC) [NCT00004011]Phase 3354 participants (Actual)Interventional1999-10-31Completed
High Dose Ifosfamide, Carboplatin and Etoposide With Amifostine Chemoprotection [NCT00003657]Phase 224 participants (Actual)Interventional1998-07-31Completed
Phase II Trial of Paclitaxel, Carboplatin and Topotecan With G-CSF in Untreated Patients With Extensive Small Cell Lung Cancer [NCT00004137]Phase 288 participants (Actual)Interventional1999-10-31Completed
Pilot Study of Intraperitoneal (IP) Therapy With Cisplatin or Carboplatin and Floxuridine (FUdR) as Consolidation for Ovarian and Gastrointestinal Malignancies [NCT00005049]Phase 245 participants (Actual)Interventional1997-05-31Completed
A Phase II Trial Using Multiple Cycles of High Dose Sequential Carboplatin, Paclitaxel and Topotecan With Peripheral Blood Stem Cell (PBSC) Support as Initial Chemotherapy in Patients With Optimally Debulked Stage III Ovarian and Primary Peritoneal Carcin [NCT00004221]Phase 212 participants (Actual)Interventional1999-11-30Terminated
Phase I (Tumour Site Specific) Study of Carboplatin and Temozolomide in Patients With Advanced Melanoma [NCT00003747]Phase 130 participants (Anticipated)Interventional1998-10-31Active, not recruiting
Phase II Trial of Carboplatin Plus Docetaxel With Day 2 Pegylated G-CSF (Neulasta®) in the Front-line Treatment of Patients With Advanced Stage Ovarian Carcinoma [NCT02469116]Phase 218 participants (Actual)Interventional2006-01-31Terminated(stopped due to Sponsor withdrew financial support)
A Phase II Study of Pemetrexed and Carboplatin in the Treatment of Esophageal Cancer [NCT00383266]Phase 29 participants (Actual)Interventional2006-10-31Terminated(stopped due to Low accrual)
Cytoreduction and Stem Cell Mobilization With Rituximab and ICE for Patients With Refractory or Relapsed CD20+ B-Cell IGL Eligible for ASCT: The RICE Protocol [NCT00005631]Phase 20 participants Interventional1999-11-30Completed
Comparison of High Dose Rapid Schedule With Conventional Schedule Chemotherapy for Stage 4 Neuroblastoma Over the Age of One Year [NCT00365755]Phase 30 participants InterventionalCompleted
A Phase I, Dose Escalation Study to Assess the Safety and Tolerability of Lapatinib in Combination With Carboplatin, Paclitaxel, With and Without Trastuzumab in Subjects With Metastatic Breast Cancer [NCT00367471]Phase 131 participants (Actual)Interventional2006-12-07Completed
Phase I Study of Dose Escalation Using Image-guided Radiotherapy to Deliver a Stereotactic Radiosurgical Boost After Neoadjuvant Chemoradiotherapy in Patients With Locally Advanced Esophageal Cancer [NCT00368329]Phase 14 participants (Actual)Interventional2006-06-30Terminated(stopped due to low accrual)
a Clinical Trial Phase II Prospective, Single-arm Study of Recombinant Human Angioendostatin /PD-1 Mab Combined With First-line Chemotherapy in the Treatment of Driver Gene Negative Advanced Non-small Cell Lung Cancer [NCT05448781]Phase 238 participants (Anticipated)Interventional2022-07-20Not yet recruiting
Efficacy and Safety of Postoperative Adjuvant Chemotherapy Combined With Camrelizumab for Patients With ⅡA -ⅢA Non-small Cell Lung Cancer：a Phase II , Single-arm Clinical Study [NCT05825443]Phase 257 participants (Anticipated)Interventional2023-04-10Recruiting
From Liquid Biopsy to Cure: Using ctDNA Detection of Minimal Residual Disease to Identify Patients for Curative Therapy After Lung Cancer Resection [NCT04966663]Phase 266 participants (Anticipated)Interventional2022-03-28Recruiting
A Multicenter, Prospective, Randomized Trial Comparing Paclitaxel and Carboplatin or Bleomycin, Etoposide and Cisplatin in the Treatment of Ovarian Malignant Sex Cord-Stromal Tumors [NCT02429700]Phase 3132 participants (Anticipated)Interventional2015-04-30Recruiting
A Multicenter, Prospective, Randomized Trial Comparing Paclitaxel and Carboplatin or Bleomycin, Etoposide and Cisplatin in the Treatment of Malignant Ovarian Germ Cell Tumors [NCT02429687]Phase 3129 participants (Anticipated)Interventional2015-04-30Recruiting
A RANDOMIZED, DOUBLE-BLIND PHARMACOKINETIC STUDY OF PF-05280014 PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN VERSUS HERCEPTIN (REGISTERED) PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN FOR THE NEOADJUVANT TREATMENT OF PATIENTS WITH OPERABLE HER2-POSITIVE BREAS [NCT02187744]Phase 3226 participants (Actual)Interventional2014-09-23Completed
A Phase II Study of Nivolumab in Combination With Carboplatin and Pemetrexed, or Nivolumab in Combination With Ipilimumab, in Patients With Advanced, EGFR-mutant or ALK-rearranged, Non-Small Cell Lung Cancer [NCT03256136]Phase 29 participants (Actual)Interventional2017-11-22Completed
A Multicenter, Randomized, Double Blind, Phase III Study of BAT1706 Versus EU Avastin® Plus Chemotherapy in Patients With Advanced Non Squamous Non Small Cell Lung Cancer [NCT03329911]Phase 3651 participants (Actual)Interventional2017-10-20Completed
Efficacy and Safety of Conventional and Low-dose Platinum Gemcitabine Combined With Cindilimab With Delayed Administration in First-line Treatment of Advanced Squamous Non-small Cell Lung Cancer [NCT05312840]Phase 460 participants (Anticipated)Interventional2022-01-01Recruiting
A Phase II Study of Breast Cancer Treatment Using Weekly Carboplatin+Nab-paclitaxel, Plus Trastuzumab (HER2+) or Bevacizumab (HER2-) in the Neoadjuvant Setting [NCT00618657]Phase 2127 participants (Actual)Interventional2008-02-29Completed
A First-in-Human Study of Repeat Dosing With REGN2810, a Monoclonal, Fully Human Antibody to Programmed Death - 1 (PD-1), as Single Therapy and in Combination With Other Anti-Cancer Therapies in Patients With Advanced Malignancies [NCT02383212]Phase 1398 participants (Actual)Interventional2015-02-02Completed
A Phase II Study of Evaluation of Cetuximab (ERBITUX) and Concurrent Carboplatin, Paclitaxel & Radiotherapy in the Management of Patients With Advanced Locoregional Squamous Cell Carcinomas of the Head and Neck [NCT00343083]Phase 243 participants (Actual)Interventional2004-12-31Completed
Phase II Study of Dose Attenuated Chemotherapy in Patients With Lung Cancer and Age > 70 and/or Comorbidities [NCT05800587]Phase 2280 participants (Anticipated)Interventional2023-02-22Recruiting
Neoadjuvant Toripalimab Combined With Chemotherapy in Rare Mutations Stage IIB-IIIB NSCLC [NCT05800340]Phase 230 participants (Anticipated)Interventional2023-04-04Recruiting
A Randomized, Double-blind, Placebo-controlled Phase III Study to Evaluate GLS-010 Plus Platinum-containing Chemotherapy With or Without Bevacizumab as First-line Treatment for Persistent, Recurrent, or Metastatic Cervical Cancer [NCT05798819]Phase 3424 participants (Anticipated)Interventional2023-05-01Not yet recruiting
A Randomized Phase 3 Multicenter Open-Label Study to Compare the Efficacy of YK-029A as First-Line Treatment Versus Platinum-Based Chemotherapy in Patients With Non-Small Cell Lung Cancer With EGFR Exon 20 Insertion Mutations [NCT05767892]Phase 3350 participants (Anticipated)Interventional2023-05-01Not yet recruiting
A Study of Nivolumab in Combination With Ipilimumab (Part 1); and Nivolumab Plus Ipilimumab in Combination With Chemotherapy (Part 2) as First Line Therapy in Stage IV Non-Small Cell Lung Cancer (NSCLC) [NCT02659059]Phase 2324 participants (Actual)Interventional2016-02-15Completed
Alkylator-Intense Conditioning Followed by Autologous Transplantation for Patients With High Risk or Relapsed Solid or CNS Tumors [NCT01505569]20 participants (Anticipated)Interventional2011-10-20Recruiting
Phase II Study of Biweekly Carboplatin and Gemcitabine With Bevacizumab as 1st Line Treatment in Patients With Advanced, Inoperable Stage IIIb/IV NSCLC [NCT00400803]Phase 238 participants (Actual)Interventional2007-03-31Completed
Phase I/II Multicenter Trial of Intra-Arterial Carboplatin and Oral Temozolomide for the Treatment of Recurrent and Symptomatic Residual Brain Metastases. [NCT00362817]Phase 1/Phase 217 participants (Actual)Interventional2004-10-31Completed
Combination Chemotherapy of Paclitaxel and Carboplatin With or Without Anthracycline as an Adjuvant Treatment in Endometrial Carcinoma [NCT06102252]80 participants (Anticipated)Interventional2023-11-30Not yet recruiting
"A Pilot Phase II Trial of Radiation Therapy Sandwiched Between Paclitaxel and Carboplatin in Patients With High-Risk Endometrial Cancer After Standard Surgical Staging" [NCT01041027]Phase 231 participants (Actual)Interventional2009-01-16Terminated(stopped due to Due to slow accrual. Results from the PORTEC3 the study rendered the hypothesis no longer valid.)
A Phase II Study of Bortezomib in Combination With Carboplatin in Patients With Metastatic Pancreatic Cancer [NCT00416793]Phase 29 participants (Actual)Interventional2006-12-31Terminated(stopped due to Study was terminated due to poor accrual)
Autologous Blood and Marrow Transplantation for Hematologic Malignancies and Selected Solid Tumors [NCT00536601]174 participants (Actual)Interventional2006-06-29Completed
A Phase II/III Study Comparing HX008 (a Humanized Monoclonal Antibody Against PD-1) Plus Chemotherapy With Pembrolizumab Plus Chemotherapy as the First-line Treatment in Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer. [NCT04750083]Phase 2/Phase 3700 participants (Anticipated)Interventional2020-09-25Recruiting
An Open-label Phase 1b Study of ARQ 092 in Combination With Other Antineoplastic Agents in Subjects With Selected Solid Tumors [NCT02476955]Phase 141 participants (Actual)Interventional2015-06-09Terminated
A Multicenter Open-Label Single-Arm Phase II Study Evaluating the Safety and Efficacy of Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Metastatic, Recurrent or Persistent Cervical Cancer [NCT02467907]Phase 2152 participants (Actual)Interventional2015-07-28Completed
BRE-01: Phase 2 Trial of Neoadjuvant Weekly Carboplatin Plus Paclitaxel Followed by Doxorubicin and Cyclophosphamide in Triple Negative Breast Cancer [NCT04083963]Phase 213 participants (Actual)Interventional2019-08-09Active, not recruiting
A Randomized Non-comparative Phase II Study of Anti-PDL1 ATEZOLIZUMAB (MPDL3280A) or Chemotherapy as Second-line Therapy in Patients With Small Cell Lung Cancer (SCLC) [NCT03059667]Phase 273 participants (Actual)Interventional2017-03-13Completed
Feasibility IB Trial of Paclitaxel/Carboplatin + Galunisertib (a Small Molecule Inhibitor of the Kinase Domain of Type 1 TGF-B Receptor) in Patients With Newly Diagnosed, Persistent or Recurrent Carcinosarcoma of the Uterus or Ovary [NCT03206177]Phase 126 participants (Actual)Interventional2017-08-20Active, not recruiting
Fluzoparib Combined With Camrelizumab for Maintenance Treatment of Locally Advanced Non-small Cell Lung Cancer After Concurrent Chemotherapy and Radiotherapy. A Single-arm, Single-center, Phase II Clinical Study [NCT04828395]Phase 265 participants (Anticipated)Interventional2021-03-01Recruiting
A Randomized, Double-blind, Placebo Controlled Phase III Study to Investigate Efficacy and Safety of First-Line Treatment With HLX10 (Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection) + Chemotherapy (Carboplatin/Cisplatin and Paclitaxel) vs C [NCT04806945]Phase 30 participants (Actual)Interventional2022-09-30Withdrawn(stopped due to The sponsor terminated the trial.)
To Predict Efficacy by Detecting Circulating Endothelial Cell Subsets and Blood Perfusion Parameters Changes in Vivo Tumor in Study of QL1101 and Avastin® in Patients With Non-squamous Non-small Cell Lung Cancer [NCT03195569]15 participants (Anticipated)Observational [Patient Registry]2017-03-01Recruiting
RANDOMISED CLINICAL TRIAL OF IFOSFAMIDE, CARBOPLATIN AND ETOPOSIDE WITH MID-CYCLE VINCRISTINE (VICE) VERSUS STANDARD PRACTICE CHEMOTHERAPY IN PATIENTS WITH LIMITED STAGE SMALL CELL LUNG CANCER (SCLC) AND GOOD PERFORMANCE STATUS [NCT00002822]Phase 3400 participants (Anticipated)Interventional1996-03-31Completed
A Randomized, Multicenter, Open-label, Phase III Trial Comparing Anthracyclines Followed by Taxane Versus Anthracyclines Followed by Taxane Plus Carboplatin as (Neo) Adjuvant Therapy in Patients With Triple-negative Breast Cancer [NCT02441933]Phase 3840 participants (Anticipated)Interventional2015-12-31Recruiting
Phase II Single-arm Clinical Study of Camrelizumab Combined With Apatinib Mesylate and Standard Chemotherapy (Pemetrixed +Carboplatin) in Patients With Tyrosine Kinase Inhibitor Failure in ALK-positive Advanced NSCLC [NCT04425135]Phase 259 participants (Anticipated)Interventional2020-07-31Not yet recruiting
B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021 (B-NHL-M-2021) [NCT05518383]Phase 4300 participants (Anticipated)Interventional2022-05-25Recruiting
A Randomized, Double-Blind, Phase III Study to Compare the Efficacy and Safety of Sintilimab (IBI308) in Combination With Gemcitabine and Platinum-Based Chemotherapy vs. Placebo in Combination With Gemcitabine and Platinum-Based Chemotherapy as First-Line [NCT03629925]Phase 3357 participants (Actual)Interventional2018-09-28Completed
Clinical Study Comparing the Efficacy and Safety of Traditional Herbal Medicine for Cancer Immunotherapy Combined With Neoadjuvant Therapy Versus Neoadjuvant Therapy in Patients With Stage II-III Breast Cancer. [NCT05483439]Phase 2100 participants (Anticipated)Interventional2021-10-20Recruiting
Pharmacokinetic Study of Carboplatin in Pediatric Hematopoietic Stem Cell Transplantation [NCT02339753]Phase 224 participants (Anticipated)Interventional2015-01-31Recruiting
A Phase III, Randomized, Open-Label, Multi-Center, Safety and Efficacy Study to Evaluate Nab-Paclitaxel (Abraxane®) as Maintenance Treatment After Induction With Nab-Paclitaxel Plus Carboplatin in Subjects With Squamous Cell Non-Small Cell Lung Cancer (NS [NCT02027428]Phase 3427 participants (Actual)Interventional2014-02-11Completed
Pilot Safety Trial of Preoperative Chemotherapy Combined With Dendritic Cell Vaccine in Patients With Locally Advanced, Triple-Negative Breast Cancer or ER-Positive, Her2-Negative Breast Cancer [NCT02018458]Phase 1/Phase 210 participants (Actual)Interventional2014-05-31Completed
A Pilot Study of SGT-53 With Carboplatin and Pembrolizumab in Metastatic Triple Negative Inflammatory Breast Cancer [NCT05093387]Phase 10 participants (Actual)Interventional2022-11-10Withdrawn(stopped due to funding issues and pharmacy preparation for the drug)
A Phase II, Prospective, Single-center, Randomized, Controlled Study of TC(Docetaxel and Carboplatin) Regimen With or Without Nimotuzumab in Recurrent Metastatic Oral Squamous Cell Carcinoma [NCT04367909]Phase 268 participants (Anticipated)Interventional2020-06-21Recruiting
SUNRAY-01, A Global Pivotal Study in Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic Non-Small Cell Lung Cancer Comparing First-Line Treatment of LY3537982 and Pembrolizumab vs Placebo and Pembrolizumab in Those With PD-L1 Expression ≥5 [NCT06119581]Phase 31,016 participants (Anticipated)Interventional2024-01-03Not yet recruiting
Phase II Pilot Study of Performance Status 2 vs. Performance Status 0-1 Non-Small Cell Lung Cancer Patients Treated With Chemo/Immunotherapy [NCT04253964]Phase 280 participants (Anticipated)Interventional2020-07-01Recruiting
Phase II Single Arm Study of Combination Pembrolizumab, Paclitaxel, and Carboplatin in Patients With Advanced Stage Ovarian, Fallopian Tube, or Peritoneal Carcinoma Receiving Neoadjuvant Chemotherapy [NCT02834975]Phase 226 participants (Actual)Interventional2016-12-22Terminated(stopped due to Investigator left institution)
A Randomized Phase II Clinical Trial Assessing the Efficacy and Safety of MK-3475 (Pembrolizumab) in Combination With Carboplatin and Gemcitabine in Patients With Metastatic Triple Negative Breast Cancer [NCT02755272]Phase 287 participants (Anticipated)Interventional2016-05-31Active, not recruiting
A Phase III, Open-label, Multicenter Trial of Avelumab (MSB0010718C) Versus Platinum-based Doublet as a First-line Treatment of Recurrent or Stage IV PD-L1+NSCLC [NCT02576574]Phase 31,214 participants (Actual)Interventional2015-10-29Active, not recruiting
A Phase Ib/II Study of AK112#PD-1/VEGF Bispecific Antibody# in Combination With AK117#Anti-CD47 Antibody# in Advanced Malignant Tumors [NCT05229497]Phase 1/Phase 2114 participants (Anticipated)Interventional2022-05-04Recruiting
A Phase I Study of Estramustine, Taxotere and Carboplatin (ETP) in Patients With Horomone Refractory Prostate Cancer [NCT00005627]Phase 10 participants Interventional1999-03-31Completed
A Randomized Trial of Trastuzumab Deruxtecan and Biology-Driven Selection of Neoadjuvant Treatment for HER2-positive Breast Cancer: ARIADNE [NCT05900206]Phase 2370 participants (Anticipated)Interventional2023-10-09Recruiting
A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5745 as Monotherapy and in Combination With Chemotherapy in Subjects With Advanced Solid Tumors [NCT01803282]Phase 1236 participants (Actual)Interventional2013-03-29Completed
Phase III Comparison of Thoracic Radiotherapy Regimens in Patients With Limited Small Cell Lung Cancer Also Receiving Cisplatin and Etoposide [NCT00632853]Phase 3731 participants (Actual)Interventional2008-03-31Active, not recruiting
Clinical Study of Neoadjuvant Anti-PD-1 Drug Toripalimab Combined With Chemotherapy in the Treatment of Locally Advanced Epithelial or Mixed Tissue Malignant Pleural Mesothelioma [NCT04713761]Phase 215 participants (Anticipated)Interventional2021-02-01Not yet recruiting
A Global Study of Novel Agents in Paediatric and Adolescent Relapsed and Refractory B-cell Non-Hodgkin Lymphoma [NCT05991388]Phase 2/Phase 3210 participants (Anticipated)Interventional2023-10-31Not yet recruiting
A Randomized, Double-blind, Phase III Trial to Compare the Efficacy and Safety of AK104 Combined With Chemotherapy to Tislelizumab Combined With Chemotherapy as First-line Treatment in PD-L1 TPS < 1% Non-small Cell Lung Cancer (NSCLC) [NCT05990127]Phase 3642 participants (Anticipated)Interventional2023-11-14Not yet recruiting
Identification of Predictive Biomarkers of Response to Chemotherapy and Immune Checkpoint Inhibitors in Early Triple Negative Breast Cancer: an Integrative Multiomics Platform [NCT05916755]100 participants (Anticipated)Observational2023-01-13Recruiting
A Pilot Window of Opportunity Study Evaluating Durvalumab (MEDI4736) in Combination With Platinum Doublet Chemotherapy Followed by Evaluation of Durvalumab (MEDI4736) in Combination With Platinum Doublet Chemotherapy and Abequolixron (RGX-104) in Non-smal [NCT05911308]Phase 124 participants (Anticipated)Interventional2023-11-30Not yet recruiting
A Phase II Trial of Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma [NCT05821088]Phase 237 participants (Anticipated)Interventional2023-06-29Recruiting
Phase II Clinical Trial of Neo-adjuvant Chemo/Immunotherapy Followed by Adjuvant Treatment Depending on the Resection Status for the Treatment of NSCLC Patients Diagnosed With Pancoast Tumor. A Multicenter Exploratory Study [NCT05684276]Phase 240 participants (Anticipated)Interventional2023-05-12Recruiting
Retrospective Observational Study of Resectable Stage IIIA Non-small Cell Lung Cancer Patients: Pathological Response After Neoadjuvant Treatment and Patient Outcomes [NCT05167487]150 participants (Anticipated)Observational2021-12-13Recruiting
Nivolumab Plus Ipilimumab Plus Two Cycles of Platinum-based Chemotherapy as First Line Treatment for Stage IV/Recurrent Non-small Cell Lung Cancer (NSCLC) Patients With Synchronous Brain Metastases [NCT05012254]Phase 271 participants (Anticipated)Interventional2021-11-18Recruiting
Upifitamab Rilsodotin (Xmt-1536) An Open-Label, Multicenter, Dose Escalation And Expansion Study Of Upifitamab Rilsodotin In Combination With Carboplatin In Participants With High Grade Serous Ovarian Cancer (Upgrade-A) [NCT04907968]Phase 131 participants (Actual)Interventional2021-06-11Terminated(stopped due to Study Terminated by Sponsor)
A Phase II Trial of Atezolizumab Plus Induction Chemotherapy (CT) Plus Chemo-radiotherapy and Atezolizumab Maintenance Therapy in Non-resectable Stage IIIA-IIIB Non-small Cell Lung Cancer (NSCLC) Patients [NCT04776447]Phase 251 participants (Anticipated)Interventional2021-06-16Recruiting
A Phase II Trial of AK112 (PD1/VEGF Bispecific) in Combination With Chemotherapy in Patients With NSCLC [NCT04736823]Phase 2296 participants (Anticipated)Interventional2021-02-01Recruiting
A Phase II Trial of Neoadjuvant Treatment Carboplatin-Pemetrexed-Bevacizumab Plus Atezolizumab for the Treatment of Locally Advanced and Potentially Resectable NSCLC Patients With EGFR Mutations [NCT04512430]Phase 226 participants (Anticipated)Interventional2020-12-02Recruiting
Induction Durvalumab Followed by Chemoradiation and Consolidation Durvalumab (MEDI4736) for Stage III Non-small Cell Lung Cancer [NCT04364048]Phase 210 participants (Actual)Interventional2020-06-18Active, not recruiting
An Open-label, Randomized, Phase 2/3 Study of Olaparib Plus Pembrolizumab Versus Chemotherapy Plus Pembrolizumab After Induction of Clinical Benefit With First-line Chemotherapy Plus Pembrolizumab in Participants With Locally Recurrent Inoperable or Metas [NCT04191135]Phase 2462 participants (Actual)Interventional2019-12-19Active, not recruiting
Phase II Open Label Nonrandomized Trial of the Anti PD 1 Therapy Pembrolizumab With First Line Platinum Based Chemotherapy Followed by 12 Months Pembrolizumab Monotherapy for Patients With Stage III/IV Epithelial Ovarian Cancer [NCT02766582]Phase 229 participants (Actual)Interventional2016-10-31Active, not recruiting
An Open-Label, Multicenter, Randomized, Phase Ib/II Study of E7080 in Combination With Carboplatin + Gemcitabine Versus Carboplatin + Gemcitabine Alone as Second Line Therapy in Patients With Platinum-Sensitive Recurrent Ovarian Cancer by CA125. [NCT01133756]Phase 1/Phase 27 participants (Actual)Interventional2010-03-31Terminated(stopped due to poor accrual)
Phase III Trial of Methotrexate, Vinblastine, Doxorubicin and Cisplatin vs Carboplatin and Paclitaxel in Advanced Carcinoma of the Urothelium [NCT00003376]Phase 3330 participants (Anticipated)Interventional1998-12-03Completed
Phase II Study of Nimotuzumab in Combination With Neoadjuvant Chemotherapy for Cervical Cancer [NCT02039791]Phase 220 participants (Anticipated)Interventional2013-01-31Active, not recruiting
Randomised, Controlled Study Comparing Chemotherapy Plus Intercalated EGFR-Tyrosine Kinase Inhibitors Combination Therapy With EGFR-Tyrosine Kinase Inhibitors Alone Therapy as First-line Treatment for Patients With Non-Small-Cell Lung Cancer [NCT02031601]Phase 4250 participants (Anticipated)Interventional2014-01-31Recruiting
Phase I-II Study Chemoradiation in Elderly Patients With Oesophagus Cancer [NCT02735057]Phase 1/Phase 254 participants (Anticipated)Interventional2016-04-30Recruiting
Nab-paclitaxel Versus Solvent-based Taxanes As First-Line Treatment for Patients With Advanced Ovarian Cancer [NCT05737303]Phase 3538 participants (Anticipated)Interventional2023-02-24Recruiting
The Efficacy of the Addition of TRAstuzumab and Pertuzumab to Neoadjuvant Chemoradiation: a Randomized Multi-center Study in Resectable HER2 Overexpressing Adenocarcinoma of the Esophagus or Gastroesophageal Junction. The TRAP-2 Study [NCT05188313]Phase 3376 participants (Anticipated)Interventional2022-03-09Recruiting
Phase I/II Trial of Carboplatin, Bevacizumab and Pemetrexed in the First-Line Treatment of Patients With Malignant Pleural Mesothelioma (MPM) [NCT00604461]Phase 1/Phase 213 participants (Actual)Interventional2007-10-31Terminated(stopped due to Slow Accrual)
Phase I/II Study of Neoadjuvant Carboplatin, Eribulin Mesylate and Trastuzumab (ECH) for Operable HER2 Positive Breast Cancer [NCT01388647]Phase 1/Phase 212 participants (Actual)Interventional2011-08-31Terminated(stopped due to Closed early due to increased hematologic toxicity and possible reduced efficacy)
Randomized Study Assessing Two Strategies of First Line: a Strategy With Intraperitoneal Chemotherapy and a Strategy With Total Intravenous Strategy, in Patients With Epithelial Advanced Ovarian Cancer [NCT03025477]Phase 284 participants (Anticipated)Interventional2016-10-31Recruiting
Optimization of Treatment Strategy for Unresectable cN3 Esophageal Squamous Cell Carcinoma: a Phase Ⅱ Single Arm Prospective Study [NCT06122493]Phase 248 participants (Anticipated)Interventional2022-11-01Recruiting
A Phase 1, Pharmacologic and Pharmacodynamic Study of MM-121 in Combination With Multiple Anticancer Therapies in Patients With Advanced Solid Tumors [NCT01447225]Phase 143 participants (Actual)Interventional2011-10-31Completed
Phase II Study on the Use of Molecular Analyses-Based Customized Chemotherapy in Patients With Stage IV/IIIB (Malignant Pleural Effusion) Non-Small-Cell Lung Cancer (NSCLC) [NCT00215930]Phase 253 participants (Actual)Interventional2004-02-29Completed
Phase 2 Trial of Response-Based Radiation Therapy for Patients With Localized Central Nervous System Germ Cell Tumors (CNS GCT) [NCT01602666]Phase 2262 participants (Actual)Interventional2012-05-29Active, not recruiting
Phase II Trial of Induction Therapy With Cetuximab (C225) and Carboplatin/Paclitaxel Chemotherapy in Previously Untreated Patients With Advanced (Stage IV) Head & Neck Squamous Cell Carcinoma [NCT00301028]Phase 248 participants (Actual)Interventional2006-04-30Completed
Induction Therapy for Locally Advanced, Resectable Cancer of the Esophagus, Gastroesophageal (GE) Junction and Gastric Cancer: A Phase I Trial of ZD6474 (Zactima, Vandetanib), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surg [NCT01183559]Phase 19 participants (Actual)Interventional2008-08-07Completed
A Phase II Trial of Topotecan and Carboplatin in the First-Line Treatment of Patients With Extensive Stage Small Cell Lung Cancer [NCT00305942]Phase 261 participants (Actual)Interventional2006-03-31Completed
A Phase II Trial of Amrubicin and Carboplatin With Pegfilgrastim in Patients With Extensive-Stage Small Cell Lung Cancer [NCT01076504]Phase 281 participants (Actual)Interventional2009-12-31Completed
Immunotherapy With Chemotherapy and Chemoradiation for Advanced Squamous Cancer of Nasal Cavity / Paranasal Sinuses (I-NAPA) [NCT05027633]Phase 235 participants (Anticipated)Interventional2021-11-02Recruiting
Carboplatin-Paclitaxel Induction Chemotherapy and ABT-888 (Veliparib) - a Phase 1/Randomized Phase 2 Study in Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT01711541]Phase 1/Phase 224 participants (Actual)Interventional2012-10-22Completed
A Phase 2/3, Multi-Center, Open-Label, Randomized Study of Weekly Nab®-Paclitaxel in Combination With Gemcitabine or Carboplatin, Compared to Gemcitabine/Carboplatin, as First Line Treatment in Subjects With ER, PgR, and HER2 Negative (Triple Negative) Me [NCT01881230]Phase 2/Phase 3191 participants (Actual)Interventional2013-09-26Completed
A Randomized Phase II Study of Individualized Combined Modality Therapy for Stage III Non-small Cell Lung Cancer (NSCLC) [NCT01822496]Phase 259 participants (Actual)Interventional2013-11-04Terminated
A Randomized Phase 2/3 Study of Eryaspase in Combination With Gemcitabine and Carboplatin Chemotherapy Versus Chemotherapy Alone for the Treatment of Patients With Metastatic or Locally Recurrent Triple-Negative Breast Cancer [NCT03674242]Phase 2/Phase 327 participants (Actual)Interventional2019-06-13Terminated(stopped due to sponsor decision)
Neoadjuvant Durvalumab/Anlotinib /Chemotherapy Plus Curative Resection in Stage III Non-Small-Cell Lung Cancer : A Single-arm Phase II Study [NCT04762030]Phase 239 participants (Anticipated)Interventional2021-02-08Recruiting
A Phase 3，Randomized，Open，Parallel Controlled, Multi-center Study of TQB2450 Injection Plus Chemotherapy Followed by TQB2450 Plus Anlotinib Versus Tislelizumab Plus Chemotherapy Followed by Tislelizumab as a First-line Treatment on Patient With Advanced N [NCT05346952]Phase 3390 participants (Anticipated)Interventional2022-01-25Recruiting
Three-Arm Randomized Phase II Study of Carboplatin and Paclitaxel in Combination With Cetuximab, IMC-A12 or Both in Patients With Advanced Non-Small Cell Lung Cancer Who Will Not Receive Bevacizumab-Based Therapy [NCT00986674]Phase 2140 participants (Actual)Interventional2009-09-30Completed
A Phase 1/1b Dose Escalation Study Evaluating Iniparib (BSI201/SAR240550) as a Single Agent and in Combination With Chemotherapeutic Regimens in Patients With Solid Tumors [NCT01455532]Phase 159 participants (Actual)Interventional2011-11-30Completed
Paediatric Hepatic International Tumour Trial [NCT03017326]Phase 3450 participants (Anticipated)Interventional2017-08-24Recruiting
A Phase II Trial of High-Dose Ascorbate in Stage IV Non-Small Cell Lung Cancer [NCT02420314]Phase 255 participants (Actual)Interventional2015-04-30Active, not recruiting
Phase I Study of Pazopanib in Combination With Weekly Paclitaxel and Carboplatin to Assess the Safety and Tolerability in Patients With Advanced Solid Tumors [NCT01407562]Phase 134 participants (Actual)Interventional2010-09-17Terminated
A Randomized, Phase 2 Study of the Efficacy and Tolerability of Veliparib in Combination With Temozolomide or Veliparib in Combination With Carboplatin and Paclitaxel Versus Placebo Plus Carboplatin and Paclitaxel in Subjects With BRCA1 or BRCA2 Mutation [NCT01506609]Phase 2294 participants (Actual)Interventional2012-01-23Completed
Treatment of Metastatic Vulvar Carcinoma With Carboplatin and Paclitaxel Chemotherapy (CRAVAT) [NCT04161664]Phase 212 participants (Anticipated)Interventional2020-01-16Recruiting
A Phase II Study Evaluating the Efficacy of Gemcitabine, Carboplatin, and Dexamethasone and Rituximab for Previously Treated Lymphoid Malignancies [NCT00072514]Phase 255 participants (Actual)Interventional2003-08-31Completed
A Phase III Randomized Trial Of Paclitaxel And Carboplatin Versus Triplet Or Sequential Doublet Combinations In Patients With Epithelial Ovarian Or Primary Peritoneal Carcinoma [NCT00011986]Phase 34,312 participants (Actual)Interventional2001-01-31Completed
An Open-label, Multi-center, Clinical Study to Evaluate Anti-PD-1 Antibody Therapies of Camrelizumab in Combination With Pemetrexed and Carboplatin as First-line Treatment in Patients With Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer [NCT05841472]Phase 260 participants (Anticipated)Interventional2023-08-23Recruiting
A Phase 1b/2 Study of BMS-986442 in Combination With Nivolumab or Nivolumab and Chemotherapies in Participants With Advanced Solid Tumors and Non-small Cell Lung Cancer [NCT05543629]Phase 1/Phase 2225 participants (Anticipated)Interventional2022-10-04Recruiting
A Phase 3 Multi-institutional Study for Treatment of Children With Newly Diagnosed Hepatoblastoma Using a Modified PHITT Strategy Incorporating a Randomized Assessment of Sodium Thiosulfate as Otoprotection for Children With Localized Disease, and Respons [NCT04478292]Phase 3330 participants (Anticipated)Interventional2021-03-01Recruiting
A Phase III, Randomised, Controlled, Multi-center, 3-Arm Study of Neoadjuvant Osimertinib as Monotherapy or in Combination With Chemotherapy Versus Standard of Care Chemotherapy Alone for the Treatment of Patients With Epidermal Growth Factor Receptor Mut [NCT04351555]Phase 3328 participants (Anticipated)Interventional2020-12-16Recruiting
A Phase 2, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial Comparing Chemoimmunotherapy (Paclitaxel-Carboplatin-Oregovomab) Versus Chemotherapy (Paclitaxel-Carboplatin-Placebo) as Neoadjuvant Therapy in Patients With Advanced Epithelial Ovari [NCT05605535]Phase 288 participants (Anticipated)Interventional2023-02-07Recruiting
Neoadjuvant PD-1 Antibody Plus Chemotherapy in Resectable Stage IIIA-N2 Non-Small-Cell Lung Cancer: A Randomized Phase II Study [NCT04422392]Phase 293 participants (Actual)Interventional2020-07-13Terminated(stopped due to since the CheckMate816 study is published in NEJM, enrolling patients becomes difficult)
"A Pilot Phase II Trial of Radiation Therapy Sandwiched Between Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma" [NCT00231868]Phase 281 participants (Actual)Interventional2001-12-31Completed
A SINGLE SITE EVALUATION OF AMIFOSTINE FOR MUCOSAL AND HEMOPOETIC PROTECTION AND CONCURRENT CARBOPLATIN, TAXOL, RADIOTHERAPY IN THE MANAGEMENT OF PATIENTS WITH ADVANCED LOCOREGIONAL SQUAMOUS CELL CARCINOMAS OF THE HEAD AND NECK. [NCT00270790]Phase 221 participants (Actual)Interventional2002-05-31Completed
A Pilot Study of Bevacizumab Plus Carboplatin and Paclitaxel in Subjects With Advanced, Previously Untreated, Squamous Non-Small Cell Lung Cancer [NCT00318136]Phase 247 participants (Actual)Interventional2005-09-30Completed
Phase 2 Study of Bevacizumab in Combination With Carboplatin and Paclitaxel in Patients With Ovarian, Fallopian Tube or Primary Peritoneal Carcinoma [NCT00408070]Phase 25 participants (Actual)Interventional2006-10-31Terminated(stopped due to Did not meet accrual goals.)
Phase I/II Study to Evaluate the Efficacy and Safety of Combination Chemotherapy With Carboplatin, Bortezomib and Bevacizumab as First Line Therapy in Patients With Advanced Non-small Cell Lung Cancer [NCT00424840]Phase 112 participants (Actual)Interventional2006-06-30Terminated(stopped due to Poor accrual)
Phase II Clinical Trial of Carboplatin and Abraxane in Patients With Extensive Stage Small Cell Lung Cancer [NCT00454324]Phase 230 participants (Actual)Interventional2006-04-30Terminated(stopped due to slow accrual)
Randomized, Multicenter, Double-Blind, Phase 3 Trial Comparing the Efficacy of Ipilimumab Plus Etoposide/Platinum Versus Etoposide/Platinum in Subjects With Newly Diagnosed Extensive-Stage Disease Small Cell Lung Cancer (ED-SCLC) [NCT01450761]Phase 31,351 participants (Actual)Interventional2011-12-13Completed
A Phase II Study of Carboplatin, Nab-paclitaxel and Cetuximab for Induction Chemotherapy for Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT01412229]Phase 240 participants (Actual)Interventional2012-02-29Completed
Perioperative Immunoagent (Tislelizumab) Plus Chemotherapy for Locally Advanced Resectable Thoracic Oesophageal Squamous Cell Carcinoma Trail:A Prospective Single-arm,Phase II Study (PILOT Trail) [NCT06056336]Phase 273 participants (Anticipated)Interventional2023-09-07Recruiting
BeEAM (Bendamustine, Etoposide, Cytarabine, Melphalan) Versus CEM (Carboplatin, Etoposide, Melphalan) in Lymphoma Patients as a Conditioning Regimen Before Autologous Hematopoietic Cell Transplantation [NCT05813132]60 participants (Actual)Interventional2022-12-01Completed
A Phase II Study of Anti-PD-1 (Pembrolizumab) in Combination With Carboplatin to Prevent Progression After Serologic Detection of Recurrent Ovarian Cancer [NCT04387227]Phase 222 participants (Anticipated)Interventional2021-03-18Recruiting
A Multicentre Single Arm Phase II Trial Assessing the Efficacy of Immunotherapy, Chemotherapy and Stereotactic Radiotherapy to Metastases Followed by Definitive Surgery or Radiotherapy to the Primary Tumour, in Patients With Synchronous Oligo-metastatic N [NCT03965468]Phase 296 participants (Anticipated)Interventional2019-11-19Recruiting
LS1781: Phase 2 Trial of High Dose Intravenous Ascorbic Acid as an Adjunct to Salvage Chemotherapy in Relapsed / Refractory Lymphoma and Patients With Clonal Cytopenia of Undetermined Significance [NCT03418038]Phase 255 participants (Anticipated)Interventional2018-03-23Recruiting
Open-Label, Randomized Trial of Nivolumab (BMS-936558) Plus Pemetrexed/Platinum or Nivolumab Plus Ipilimumab (BMS-734016) vs Pemetrexed Plus Platinum in Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) Subjects With Epidermal Growth Factor Recepto [NCT02864251]Phase 3367 participants (Actual)Interventional2017-03-17Completed
A Phase 1/2, Open-Label, Dose Escalation, Safety and Tolerability Study of INCB050465 and Iitacitinib in Subjects With Previously Treated B-Cell Malignancies (CITADEL-101) [NCT02018861]Phase 1/Phase 288 participants (Actual)Interventional2016-09-22Completed
Predictors of Response to Neoadjuvant Docetaxel-Carboplatin Chemotherapy for Patients With Stage II and III Triple Negative Breast Cancer [NCT01560663]415 participants (Anticipated)Observational2012-01-31Active, not recruiting
A Phase I Study of MK-3475 Alone in Subjects With Advanced Solid Tumors and in Combination With Platinum-Doublet Chemotherapy or Immunotherapy in Subjects With Advanced Non-Small Cell Lung Cancer/Extensive-Disease Small Cell Lung Cancer. [NCT01840579]Phase 157 participants (Actual)Interventional2013-04-26Completed
A Randomized, Multicenter, Double-Blind, Multinational, Phase 3 Trial Comparing the Efficacy of Ipilimumab in Addition to Paclitaxel and Carboplatin Versus Placebo in Addition to Paclitaxel and Carboplatin in Subjects With Stage IV/Recurrent Non-Small Cel [NCT02279732]Phase 3342 participants (Actual)Interventional2014-10-13Completed
A Phase II, Single Arm Study of CarbopLatin Plus Etoposide With Bevacizumab and Atezolizumab in Patients With exTEnded-disease Small-cell Lung Cancer (SCLC) [NCT04730999]Phase 252 participants (Actual)Interventional2020-07-01Active, not recruiting
A Phase II Study of Neoadjuvant NAPOX Followed by Chemoradiation With Paclitaxel and Carboplatin in Locally Advanced Esophagogastric Cancer [NCT04656041]Phase 240 participants (Anticipated)Interventional2021-06-29Recruiting
Prostate Cancer Biomarker Enrichment and Treatment Selection (PC-BETS) Study [NCT03385655]Phase 2600 participants (Anticipated)Interventional2018-08-01Recruiting
A Phase 3, Multicenter, Randomized and Double-Blind Study to Assess the Similarity in Efficacy and Safety Between TRS003 and China-approved Bevacizumab in Subjects With Advanced Nonsquamous NSCLC [NCT04416035]Phase 3608 participants (Anticipated)Interventional2020-08-17Recruiting
A Comparison of Paclitaxel in Combination With Cisplatin(TP), Carboplatin(TC) or Fluorouracil(TF) Concurrent With Radiotherapy for Patients With Local Advanced Esophageal Squamous Cell Carcinoma: A Three-Arm Randomized Phase III Trial [NCT02459457]Phase 3321 participants (Actual)Interventional2015-07-01Completed
A Phase 1b/2 Double-Blind Randomized Trial of the Hedgehog/SMO Antagonist LY2940680 in Combination With Carboplatin and Etoposide Followed by LY2940680 Versus Carboplatin and Etoposide Plus Placebo Followed by Placebo in Patients With Extensive-Stage Smal [NCT01722292]Phase 1/Phase 226 participants (Actual)Interventional2013-01-31Terminated(stopped due to Change in clinical strategy.)
A Randomized Phase II Trial of Paclitaxel and Carboplatin vs. Bleomycin, Etoposide, and Cisplatin for Newly Diagnosed Advanced Stage and Recurrent Chemonaive Sex Cord-Stromal Tumors of the Ovary [NCT01042522]Phase 263 participants (Actual)Interventional2010-02-08Active, not recruiting
A Phase 1, Single-Dose, Open-Label, Randomized Cross-Over Study Evaluating the Bioavailability and Food Effect of Veliparib Tablets Followed by an Extension in Subjects With Ovarian Cancer [NCT03400306]Phase 10 participants (Actual)Interventional2021-11-15Withdrawn(stopped due to Strategic considerations)
Phase II Clinical Trial on the Combination of Carboplatin, Eribulin and Veliparib in Stage IV Cancer Patients With Homologous Recombination Deficiency [NCT03032614]Phase 20 participants (Actual)Interventional2017-09-30Withdrawn(stopped due to Lack of funding)
A Phase III, Multicenter, Open-Label, Randomized Study of Cisplatin or Carboplatin With Gemcitabine Versus Gemcitabine Alone as Adjuvant Therapy in Patients With Resected or Ablated Intra-Hepatic Cholangiocarcinoma [NCT03081039]Phase 30 participants (Actual)Interventional2017-08-21Withdrawn(stopped due to Competing study)
Randomised, Phase II/III, 3 Stage Trial to Evaluate the Safety and Efficacy of the Addition of Olaparib to Platinum-based Neoadjuvant Chemotherapy in Breast Cancer Patients With TNBC and/or gBRCA. [NCT03150576]Phase 2/Phase 3780 participants (Anticipated)Interventional2016-05-31Recruiting
Allogeneic Blood or Marrow Transplantation for Hematologic Malignancy and Aplastic Anemia [NCT00003816]Phase 2/Phase 3361 participants (Actual)Interventional1998-10-19Completed
Randomized Phase II Study of Adriamycin/Cytoxan/Taxol (ACT) vs. Cytoxan, Thiotepa, Carboplatin (STAMP V) in Patients With High-Risk Primary Breast Cancer [NCT00004092]Phase 272 participants (Actual)Interventional1999-05-31Completed
A Single-arm, Multi-center and Exploratory Study of Adebelizumab Combined With Chemotherapy and Sequential Adebelizumab Combined With Radiotherapy in the Treatment of Newly Diagnosed Extensive Small Cell Lung Cancer [NCT06125041]Phase 251 participants (Anticipated)Interventional2023-10-30Recruiting
A Phase II/III Study to Evaluate the Safety and Efficacy of BAT1308 Combined With Platinum-Based Chemotherapy ± Bevacizumab as First-Line Therapy For PD-L1-Positive (CPS ≥ 1) Persistent, Recurrent or Metastatic Cervical Cancer [NCT06123884]Phase 2/Phase 3526 participants (Anticipated)Interventional2023-11-30Not yet recruiting
A Phase II Trial of Carboplatin, Pemetrexed, and Panitumumab in Patients With Advanced Non-Squamous K-ras Wild Type Non-Small-Cell Lung Cancer [NCT01042288]Phase 270 participants (Actual)Interventional2010-06-30Completed
A Phase 3 Randomized, Open-label, Active-comparator Controlled Clinical Study of Pembrolizumab Versus Platinum Doublet Chemotherapy in Participants With Mismatch Repair Deficient (dMMR) Advanced or Recurrent Endometrial Carcinoma in the First-line Setting [NCT05173987]Phase 3280 participants (Anticipated)Interventional2022-02-03Active, not recruiting
A Phase 1 Study of NBTXR3 Activated by Radiotherapy With Concurrent Chemotherapy for Adenocarcinoma of the Esophagus [NCT04615013]Phase 124 participants (Anticipated)Interventional2020-11-23Recruiting
A Randomized Phase III, Two-Arm Trial of Paclitaxel/Carboplatin/Maintenance Letrozole Versus Letrozole Monotherapy in Patients With Stage II-IV, Primary Low-Grade Serous Carcinoma of the Ovary or Peritoneum [NCT04095364]Phase 3450 participants (Anticipated)Interventional2019-09-20Recruiting
T-Cell Immune Checkpoint Inhibition Plus Hypomethylation for Locally Advanced HER2-Negative Breast Cancer - A Phase 2 Neoadjuvant Window Trial of Pembrolizumab and Decitabine Followed by Standard Neoadjuvant Chemotherapy [NCT02957968]Phase 246 participants (Actual)Interventional2017-01-24Active, not recruiting
A Randomized, Double-Blind, Phase III Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer - (KEYNOTE-355) [NCT02819518]Phase 3882 participants (Actual)Interventional2016-07-27Completed
A Randomized, Multicenter, Open-Label, Phase 2 Study of Paclitaxel-Carboplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Paclitaxel-Carboplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Can [NCT01769391]Phase 2167 participants (Actual)Interventional2013-01-31Completed
Radiotherapy Alone Versus Chemotherapy Followed By Response-Based Radiotherapy For Newly Diagnosed Primary CNS Germinoma [NCT00085098]Phase 324 participants (Actual)Interventional2007-01-31Completed
PDL-1 Targeting in Resectable Oesophageal Cancer: a Phase II Feasibility Study of Atezolizumab and Chemoradiation. [NCT03087864]Phase 240 participants (Actual)Interventional2017-06-28Completed
A Prospective Study to Evaluate the Safety of Concurrent Durvalumab (MEDI4736) With Chemoradiation Therapy（CRT）Followed by Durvalumab for Chinese Unresectable Stage III Non Small Cell Lung Cancer（NSCLC） [NCT04982549]Phase 235 participants (Anticipated)Interventional2021-01-21Recruiting
A Single-arm, Multi-center Phase II Clinical Study of Camrelizumab Combined With Concurrent Chemoradiation in Patients With Cervical Cancer Who Had Recurrence of the Pelvic Wall After Surgery ± Abdominal Aortic Lymph Node Metastasis [NCT04974827]Phase 246 participants (Anticipated)Interventional2021-05-20Recruiting
A Multicenter Randomized Double Blind Study Examining the Efficacy and Safety of Denosumab in Combination With First Line Platinum-based Chemotherapy for Patients With Bone Metastasis Secondary to Metastatic Urothelial Cancer [NCT03520231]Phase 26 participants (Actual)Interventional2018-09-04Completed
A Phase 3, Randomized Double-blind, Placebo-controlled, Multicenter Study of SHR-1701 in Combination With Bevacizumab and Chemotherapy in Advanced or Metastatic Non-squamous Non-small-cell Lung Cancer With EGFR Mutation After Failure of TKIs [NCT05132413]Phase 3561 participants (Anticipated)Interventional2021-12-30Not yet recruiting
A Phase 1/2 Study of NC318 in Combination With Chemotherapy for Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer [NCT04430933]Phase 1/Phase 20 participants (Actual)Interventional2021-12-06Withdrawn(stopped due to Upon reviewing current available combo studies, the sponsor decided to prioritize different combo study.)
Neoadjuvant Chemotherapy and Tilelizumab in Stage III（cTNM-IIIA.IIIB）Non-small-cell Lung Cancer ,a Single-arm, Phase Ⅱ Clinical Trial [NCT04865705]Phase 233 participants (Anticipated)Interventional2020-11-10Active, not recruiting
Epirubicin-Cyclophosphamide Followed by Taxanes or Taxanes Plus Carboplatin in Triple-Negative Breast Cancer：A Prospective, Randomized, Phase III Trial [NCT02455141]Phase 3970 participants (Anticipated)Interventional2015-07-31Recruiting
Observation Study of Patients With Non-Small Cell Lung Cancer and Esophageal Cancer Treated With Chemo-Radiation Followed by Surgery [NCT03095209]6 participants (Actual)Observational2017-02-24Completed
A Single-arm, Phase II Study of Anlotinib Combined With Platinum/Gemcitabine for First Line Treatment of Advanced Urothelial Carcinoma [NCT05030077]Phase 253 participants (Anticipated)Interventional2021-10-01Not yet recruiting
A Platform Study of RAS(ON) Inhibitor Combinations in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC) [NCT06162221]Phase 1/Phase 2352 participants (Anticipated)Interventional2023-12-31Not yet recruiting
A Phase III, Randomized, Open-Label, Multicenter, Global Study of Volrustomig (MEDI5752) in Combination With Carboplatin Plus Pemetrexed Versus Platinum Plus Pemetrexed or Nivolumab Plus Ipilimumab in Participants With Unresectable Pleural Mesothelioma (e [NCT06097728]Phase 3600 participants (Anticipated)Interventional2023-11-09Recruiting
A Non Inferior, Randomized Controlled Phase II Clinical Study Comparing the Efficacy of Nab-PH+Pyrrolitinib and TCbHP in the Neoadjuvant Treatment of HER2 Positive Breast Cancer [NCT05918328]Phase 2610 participants (Anticipated)Interventional2023-05-03Active, not recruiting
A Phase 1b Study Evaluating the Safety and Efficacy of First-Line Tarlatamab in Combination With Carboplatin, Etoposide, and PD-L1 Inhibitor in Subjects With Extensive Stage Small Cell Lung Cancer [NCT05361395]Phase 1340 participants (Anticipated)Interventional2022-08-24Recruiting
A Randomized, Double-Blind, International Multicenter, Phase III Study to Evaluate the Anti-Tumor Efficacy and Safety of Serplulimab or Placebo in Combination With Chemotherapy and Concurrent Radiotherapy in Patients With Limited-Stage Small Cell Lung Can [NCT05353257]Phase 3482 participants (Anticipated)Interventional2022-05-17Recruiting
An Open-Label, Phase 1/2 Study of ORIC-114 as a Single Agent or in Combination With Chemotherapy, in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration [NCT05315700]Phase 1/Phase 2280 participants (Anticipated)Interventional2022-03-10Recruiting
An Open-Label, Multicenter, First-in-Human, Phase 1 Dose-Escalation and Multicohort Expansion Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas [NCT03715933]Phase 1240 participants (Anticipated)Interventional2018-10-10Recruiting
A Phase II Trial of Induction Paclitaxel Plus Carboplatin Followed by Thoracic Radiation Therapy With Concurrent Weekly Low-Dose Paclitaxel and Twice Weekly Amifostine for Patients With Unresectable Locally Advanced or Partially Resected Non-Small Cell Lu [NCT00003089]Phase 20 participants Interventional1997-07-31Completed
Primary Surgical Therapy for Biologically Defined Low-Risk Neuroblastoma: A Pediatric Oncology Group/Children's Cancer Group Intergroup Study [NCT00003119]Phase 3968 participants (Actual)Interventional1998-03-31Completed
A RANDOMIZED, CONTROLLED TRIAL OF SALVAGE THERAPY WITH PACLITAXEL AND CARBOPLATIN VERSU SALVAGE THERAPY WITH STEM CELL SUPPORTED HIGH-DOSE CARBOPLATIN, MITOXANTRONE AND CYCLOPHOSPHAMIDE IN PATIENTS WITH PERSISTENT LOW VOLUME OVARIAN CANCER AND RESPONSE TO [NCT00002819]Phase 30 participants Interventional1996-11-30Terminated
Randomized Phase II Trial of Carboplatin/Gemcitabine Followed By Paclitaxel or Cisplatin/Vinorelbine Followed by Docetaxel in Advanced Non-Small Cell Lung Cancer [NCT00003587]Phase 2204 participants (Actual)Interventional1998-10-31Completed
A Phase III Study of Surgical Resection and Chemotherapy (Paclitaxel and Carboplatin) With or Without Adjuvant Radiotherapy for Resected Stage IIIA Non-Small Cell Lung Cancer [NCT00003317]Phase 3480 participants (Actual)Interventional1998-05-31Completed
A Phase II Study of 3-Dimensional Conformal Hyperfractionation Radiation Therapy (3D-CHRT) With Dose Escalation and Amifostine Mucosal Protection for Patients With Favorable Prognosis Inoperable Stage II-IIIA/B Non-Small Cell Lung Cancer (NSCLC) Receiving [NCT00004253]Phase 20 participants Interventional2000-03-31Active, not recruiting
Phase I Evaluation of Topotecan in Combination With Paclitaxel and Carboplatin [NCT00005021]Phase 117 participants (Actual)Interventional1996-07-31Completed
Phase II Study of First-Line Therapy of Ovarian Cancer With Sequential Regimens: Cisplatin-Prolonged Oral Topotecan (C-PORT) Followed by Paclitaxel/Carboplatin (PC) [NCT00005051]Phase 20 participants Interventional1999-08-31Completed
Single Cell Analysis of CXCL13+PD1+ CD8 T Cell in Association With Resistance to Pembrolizumab and Chemotherapy Neoadjuvant/Adjuvant of NSCLC [NCT05894889]Phase 270 participants (Anticipated)Interventional2023-10-01Not yet recruiting
"Neoadjuvant Tislelizumab and Platinum-Based Doublet Chemotherapy in Stage II-IIIB EGFR-Mutated Lung Adenocarcinoma With PD-L1 Positive Expression -- A Phase II Study (DuoVitality)" [NCT05527808]28 participants (Anticipated)Interventional2022-08-01Recruiting
A Phase 1B Trial Evaluating the Safety of Ribociclib, Tucatinib, and Trastuzumab in Patients With Metastatic, HER2+ Breast Cancer and a Multicenter, Randomized, Open-Label, Phase 2 Study of Preoperative Treatment With Ribociclib,Ttrastuzumab, Tucatinib, a [NCT05319873]Phase 1/Phase 218 participants (Anticipated)Interventional2022-04-07Recruiting
A Parallel Arms Phase 1 Safety, Pharmacokinetic And Pharmacodynamic Study Of The Intravenous Poly (ADP-Ribose) Polymerase (PARP) Inhibitor PF-01367338 (AG-014699) In Combination With Several Chemotherapeutic Regimens In Adult Patients With Advanced Solid [NCT01009190]Phase 185 participants (Actual)Interventional2010-02-28Completed
Phase II Pilot Trial of Carboplatin, Paclitaxel, and Herceptin in HER2/Neu (+) Advanced NSCLC [NCT00003881]Phase 20 participants Interventional1999-05-31Completed
A Phase 1 First-in-Human Study Evaluating Safety, Pharmacokinetics and Efficacy of ABBV-706 as Monotherapy and in Combination With Budigalimab (ABBV-181), Carboplatin, or Cisplatin in Adult Subjects With Advanced Solid Tumors [NCT05599984]Phase 1350 participants (Anticipated)Interventional2022-12-05Recruiting
A Phase 1b, Open-Label, Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Patients With Solid Tumors [NCT01862328]Phase 164 participants (Actual)Interventional2013-06-10Completed
Multi-arm, Non-randomized, Open-Label Phase IB Study to Evaluate GSK3052230 in Combination With Paclitaxel and Carboplatin, or Docetaxel or as Single Agent in Subjects With Solid Malignancies and Deregulated FGF Pathway Signaling [NCT01868022]Phase 165 participants (Actual)Interventional2013-10-09Completed
Phase II Trial of Adjuvant Bi-shRNAfurin and GMCSF Augmented Autologous Tumor Cell Vaccine (FANG™) Integrated With Chemotherapy for Patients With Recurrent Cisplatinum Sensitive Ovarian Cancer Participating in Study CL-PTL 105 [NCT01867086]Phase 21 participants (Actual)Interventional2013-06-30Completed
A Randomized, Open-label, Multicentric, Two-arm Pivotal Trial of SonoCloud-9 Combined With Carboplatin (CBDCA) vs Standard of Care Lomustine (CCNU) or Temozolomide (TMZ) in Patients Undergoing Planned Resection for First Recurrence Glioblastoma. [NCT05902169]Phase 3560 participants (Anticipated)Interventional2023-11-05Not yet recruiting
A Phase II, Randomized, Open-label Trial of Trilaciclib Prior to Chemotherapy Plus Tislelizumab as First-line Treatment for Advanced Squamous Non-Small-Cell Lung Cancer [NCT05900921]Phase 2132 participants (Anticipated)Interventional2023-07-01Not yet recruiting
Phase 2 Trial of Neoadjuvant Nivolumab + Platinum-based Chemotherapy + Certolizumab in Patients With Resectable Stages II-III Lung Cancers [NCT04991025]Phase 260 participants (Anticipated)Interventional2022-10-19Recruiting
A Safety and Feasibility Study of AGS-003-LNG for the Treatment of Stage 3 Non Small Cell Lung Cancer [NCT02662634]Phase 20 participants (Actual)Interventional2016-03-31Withdrawn
A Open-Label, Multicenter, Randomised, Controlled Phase 3 Study of RC48-ADC Plus Toripalimab Versus Chemotherapy Alone in Previously Untreated Unresectable Locally Advanced or Metastatic Urothelial Carcinoma With HER2-Expressing [NCT05302284]Phase 3452 participants (Anticipated)Interventional2022-06-14Recruiting
An Open-Label Phase I/II Study of GSK2110183 in Combination With Carboplatin and Paclitaxel in Subjects With Platinum-Resistant Ovarian Cancer [NCT01653912]Phase 1/Phase 259 participants (Actual)Interventional2012-11-30Completed
A First-line Multi-center, Single-arm Exploratory Study Using Low-dose Radiotherapy (LDRT) Combined With Durvalumab (MEDI4736), Etoposide, and Cisplatin/Carboplatin for Patients With Extensive-stage Small Cell Lung Cancer [NCT05092412]Phase 230 participants (Anticipated)Interventional2022-03-02Recruiting
An Open Label, Multicenter Phase 2 Study of Durvalumab (MEDI4736) + Olaparib as Maintenance Therapy in Patients With Extensive Stage Small-Cell Lung Cancer [NCT05245994]Phase 260 participants (Anticipated)Interventional2021-08-21Recruiting
Bevacizumab Combined With High-Dose Gemcitabine, Docetaxel, Melphalan, and Carboplatin in Patients With Advanced Epithelial Ovarian Cancer [NCT00583622]Phase 213 participants (Actual)Interventional2007-12-31Terminated(stopped due to Slow Accrual)
BrUOG-BR-211B q3week Carboplatin With Weekly Abraxane and Trastuzumab As Neoadjuvant Therapy in Resectable and Unresectable HER2+ (Stage IIa-IIIb) Breast Cancer [NCT00617942]Phase 260 participants (Actual)Interventional2008-02-29Completed
A Phase I/II Study of Vorinostat Plus Rituximab, Ifosphamide, Carboplatin, and Etoposide for Patients With Relapsed or Refractory Lymphoid Malignancies or Untreated T- or Mantle Cell Lymphoma [NCT00601718]Phase 1/Phase 229 participants (Actual)Interventional2007-12-31Completed
A Phase II Study of Carboplatin, Nanoparticle Albumin-Bound Paclitaxel (ABI-007) and Avastin as the First Line Therapy in Metastatic Breast Cancer. [NCT00654836]Phase 232 participants (Actual)Interventional2007-10-31Completed
A Phase II Study of Capecitabine, Carboplatin, and Bevacizumab for Metastatic or Unresectable Gastroesophageal Junction and Gastric Adenocarcinoma [NCT00780494]Phase 235 participants (Actual)Interventional2009-02-28Completed
Neoadjuvant Soft Tissue Ablation Utilizing Aliya™ Pulsed Electric Fields With Systemic Therapy in Early-Stage Resectable Non-Small Cell Lung Cancer (NSCLC) [NCT05583188]Phase 415 participants (Anticipated)Interventional2023-02-01Recruiting
A Randomised, Placebo-controlled, Double-blind Phase II of Sequential Administration of Tarceva (Erlotinib) or Placebo in Combination With Gemcitabine/Platinum as First-line Treatment in Patients With Stage IIIB/IV Non-small Cell Lung Cancer (NSCLC). [NCT01998919]Phase 2154 participants (Actual)Interventional2006-08-31Completed
Alternating Treatment Plans for Participants With Advanced Thoracic/Head & Neck Cancers (ATATcH) [NCT05358548]Phase 2150 participants (Anticipated)Interventional2022-04-28Recruiting
A Randomized, Global, Open-label Study of Nivolumab in Combination With BMS-986205 vs Standard of Care EXTREME Regimen in First-line Recurrent/Metastatic Squamous Cell Carcinoma of Head and Neck [NCT03386838]Phase 30 participants (Actual)Interventional2018-03-28Withdrawn(stopped due to Business objectives have changed.)
Clinical Trial of a Rapidly Cycling, Non-Cross Reactive Regimen of Approved Therapeutic Agents to Treat Prostate Cancer [NCT02903160]Phase 240 participants (Actual)Interventional2017-01-13Completed
Phase Ib Study to Evaluate the Efficacy, Safety and Tolerability of IBI188 Combination Therapy in Subjects With Advanced Malignancies [NCT04861948]Phase 19 participants (Actual)Interventional2021-05-25Terminated(stopped due to No signs of efficacy in solid tumors)
MEK114375: A Rollover Study to Provide Continued Treatment With GSK1120212 to Subjects With Solid Tumors or Leukemia [NCT01376310]Phase 2159 participants (Actual)Interventional2010-11-02Terminated(stopped due to Company Decision)
Phase 1/2 Modular Dose Escalation With Cohort Expansion of CP-506 (HAP) in Patients With Solid Tumor Types With High Incidence of HRD/FAD in Monotherapy or With Carboplatin or Patients With Solid Tumour and OPD Receiving ICI [NCT04954599]Phase 1/Phase 2126 participants (Anticipated)Interventional2023-04-25Recruiting
A Phase 2, Randomized, Open-Label Study of Trilaciclib Administered With First-Line Platinum-Based Chemotherapy and Avelumab Maintenance Therapy in Patients With Untreated, Locally Advanced or Metastatic Urothelial Carcinoma (PRESERVE 3) [NCT04887831]Phase 292 participants (Actual)Interventional2021-06-04Active, not recruiting
A Randomized Phase II Trial of Mirvetuximab Soravtansine (IMGN853), in Folate Receptor Alpha (FRα) High Recurrent Ovarian Cancer Eligible for Platinum-based Chemotherapy. Supported by: DIAGNOSTIC PROTOCOL for the VENTANA FOLR1 (FOLR1-2.1) CDx Assay Ventan [NCT04274426]Phase 2136 participants (Anticipated)Interventional2021-10-13Recruiting
A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Car [NCT03682068]Phase 31,292 participants (Anticipated)Interventional2018-09-27Recruiting
A Phase II Trial of Atezolizumab (Anti-PDL1) With Carboplatin in Patients With Metastatic Triple Negative Breast Cancer [NCT03206203]Phase 2106 participants (Actual)Interventional2017-08-29Active, not recruiting
Concurrent Chemotherapy and Radiation Therapy for Newly Diagnosed Patients With Stage I/II Nasal NK Cell Lymphoma [NCT02106988]Phase 240 participants (Anticipated)Interventional2015-01-16Recruiting
A Phase II Study of Induction Chemotherapy Followed by Thoracic Radiotherapy and Erlotinib in Poor-Risk Stage III Non-Small Cell Lung Cancer [NCT00553462]Phase 278 participants (Actual)Interventional2008-03-31Completed
A Phase II Study of Neoadjuvant Carboplatin/Paclitaxel Followed by Dose-Dense Doxorubicin/Cyclophosphamide in Patients With Hormone Receptor Negative, HER2 Receptor Negative Breast Cancer [NCT03301350]Phase 229 participants (Actual)Interventional2017-11-07Completed
Randomized Phase III Trial Investigating the Survival Benefit of Adding Thoracic Radiotherapy to Durvalumab (MEDI4736) Immunotherapy Plus Chemotherapy in Extensive Stage Small-cell Lung Cancer [NCT05223647]Phase 3302 participants (Anticipated)Interventional2022-01-11Recruiting
Chemoimmunotherapy With Obinutuzumab, Ifosfamide, Carboplatin and Etoposide (O-ICE) in Children, Adolescents and Young Adults With Recurrent Refractory CD20+ Mature B-NHL [NCT02393157]Phase 225 participants (Anticipated)Interventional2015-08-21Recruiting
A Phase II Study of Sorafenib in Combination With Carboplatin and Paclitaxel in Metastatic or Recurrent Head and Neck Squamous Cell Cancer [NCT00494182]Phase 248 participants (Actual)Interventional2007-04-25Active, not recruiting
Next Generation Sequencing to Evaluate Breast Cancer Subtypes and Genomic Predictors of Response to Therapy in the Preoperative Setting for Stage II-III Breast Cancer [NCT01959490]Phase 216 participants (Actual)Interventional2013-09-24Completed
A Phase 3, Randomized, Open-label, Multicenter Study to Assess the Efficacy and Safety of HS-10241 Combined With Almonertinib Versus Pemetrexed Combined With Platinum in Metastatic or Locally Advanced NSCLC With MET Amplification After Failure of the Prio [NCT06110663]Phase 3314 participants (Anticipated)Interventional2023-12-30Not yet recruiting
A Phase II Trial of the Efficacy and Safety of the Combination of Cemiplimab and Low-Dose Paclitaxel and Carboplatin in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT04862650]Phase 242 participants (Anticipated)Interventional2021-11-30Recruiting
A Randomised Non-comparative Open Label Phase II Trial of Atezolizumab Plus Bevacizumab, With Carboplatin-paclitaxel or Pemetrexed, in EGFR-mutant Non-small Cell Lung Carcinoma With Acquired Resistance [NCT04245085]Phase 295 participants (Actual)Interventional2020-09-29Active, not recruiting
An Open-label, Multicenter Phase II Study to Compare the Efficacy of Carboplatin as First-line Followed by Second-line Olaparib Versus Olaparib as First-line Followed by Second-line Carboplatin in the Treatment of Patients With Castration Resistant Prosta [NCT04038502]Phase 2100 participants (Anticipated)Interventional2019-10-01Recruiting
A Randomized, Controlled, Open-Label, Phase 2 Trial of SGI-110 and Carboplatin in Subjects With Platinum-Resistant Recurrent Ovarian Cancer [NCT01696032]Phase 2120 participants (Actual)Interventional2012-09-30Completed
An Open Label Phase I/II Study of Cabazitaxel With or Without Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer [NCT01505868]Phase 1/Phase 2170 participants (Actual)Interventional2012-07-11Completed
A Multicenter Phase 3, Double-Blind, Placebo-Controlled Study Comparing Chemo-Immunotherapy (Paclitaxel-Carboplatin- Oregovomab) vs Chemotherapy (Paclitaxel-Carboplatin- Placebo) in Patients With Advanced Epithelial Ovarian, Fallopian Tube or Peritoneal C [NCT04498117]Phase 3615 participants (Actual)Interventional2020-08-25Active, not recruiting
Phase II Study of Concurrent and Sequential Carboplatin and Paclitaxel With Adjuvant Radiotherapy for High Risk Endometrial Cancer [NCT03935256]Phase 224 participants (Anticipated)Interventional2019-03-05Active, not recruiting
PD-1 Inhibitor and Chemotherapy With Concurrent Irradiation at Varied Tumour Sites in Advanced Non-small Cell Lung Cancer [NCT03774732]Phase 3327 participants (Anticipated)Interventional2019-03-21Recruiting
A Phase II Study of Concurrent IGFBP-2 Vaccination and Neoadjuvant Chemotherapy to Increase the Rate of Pathologic Complete Response at the Time of Cytoreductive Surgery [NCT03029611]Phase 211 participants (Actual)Interventional2017-04-03Terminated(stopped due to Terminated due to lack of funding)
Phase I/II, Open-Label Study of R-ICE (Rituximab-Ifosfamide-Carboplatin-Etoposide) With Lenalidomide (R2-ICE) in Patients With First-Relapse/Primary Refractory Diffuse Large B-Cell Lymphoma (DLBCL) [NCT02628405]Phase 1/Phase 263 participants (Actual)Interventional2016-05-20Active, not recruiting
A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial Comparing the Efficacy and Safety of a Sintilimab Plus ICE Regimen Versus a Placebo Plus ICE Regimen in Classic Hodgkin's Lymphoma Patients With First-line Standard Chemotherapy [NCT04044222]Phase 3240 participants (Anticipated)Interventional2019-10-21Recruiting
A Phase 3 Study of Pembrolizumab in Combination With Carboplatin/Taxane (Paclitaxel or Nab-paclitaxel) Followed by Pembrolizumab With or Without Maintenance Olaparib in the First-line Treatment of Metastatic Squamous Non-small Cell Lung Cancer (NSCLC) [NCT03976362]Phase 3857 participants (Anticipated)Interventional2019-06-28Active, not recruiting
Phase 2 Study of Platinum-Based Chemotherapy in Combination With Durvalumab (MEDI 4736) for NSCLC in Patients With a Poor Performance Status and the Elderly [NCT04262869]Phase 20 participants (Actual)Interventional2020-03-27Withdrawn(stopped due to Due to accrual issues)
A Randomized, Open-label, Multiple-centre Study of Intercalating and Maintenance Gefitinib in Combination With Chemotherapy for Advanced NSCLC With EGFR Mutation Positive [NCT02299765]Phase 461 participants (Actual)Interventional2014-12-31Terminated(stopped due to the research data is not statistically significant)
Phase 2: A Randomized Controlled Study on Effectiveness of Chemotherapy (Carboplatin-Paclitaxel) Versus Chemo-immunotherapy (Carboplatin-Paclitaxel-Oregovomab) in Patients With Advanced Epithelial Ovarian, Adnexal or Peritoneal Carcinoma [NCT01616303]Phase 297 participants (Actual)Interventional2012-06-15Completed
A Two-Part, Open Label Phase II Trial: Part One, Dose Escalation Safety; Part Two, Randomized/Comparing CDP791 Plus Carboplatin/Paclitaxel With Carboplatin/Paclitaxel Alone in Subjects With Locally Advanced or Metastatic Non-Squamous Non-Small-Cell Lung C [NCT00152477]Phase 2165 participants (Actual)Interventional2005-08-15Completed
TCH (Docetaxel/Carboplatin/Trastuzumab) Versus EC -TH(Epirubicin/Cyclophosphamide Followed by Docetaxe/Trastuzumab) as Neoadjuvant Treatment for HER2-Positive Breast Cancer [NCT03140553]Phase 2140 participants (Actual)Interventional2016-09-01Completed
A Randomized Double-Blinded Phase II Study of Carboplatin/Paclitaxel/CT-322 Versus Carboplatin/Paclitaxel/Bevacizumab as First-Line Treatment for Recurrent or Advanced Non-Small Cell Lung Cancer With Non-Squamous Histology [NCT00850577]Phase 2255 participants (Actual)Interventional2009-06-30Terminated
A Multi-Centre Phase II Study Using Carboplatin AUC-10 for Metastatic Seminoma With IGCCCG Good Prognosis Disease-Therapy Directed by Initial Metabolic Response on PET-CT [NCT02272816]Phase 248 participants (Actual)Interventional2012-02-13Completed
Randomized Trial of Neo-adjuvant Chemotherapy With or Without Metformin for HER2 Positive Operable Breast Cancer [NCT03238495]Phase 2100 participants (Anticipated)Interventional2017-08-15Recruiting
Combination of the Hypomethylating Agent Decitabine and the Nuclear Export Receptor XPO-1 Inhibitor Selinexor to Reverse Platinum Resistance in Relapsed/Refractory Epithelial Ovarian Cancer [NCT05983276]Phase 240 participants (Anticipated)Interventional2023-08-28Not yet recruiting
Study of Utidelone Based Neoadjuvant Treatment on Early High-risk or Locally Advanced Breast Cancer [NCT05983094]Phase 2181 participants (Anticipated)Interventional2023-09-01Not yet recruiting
A Phase 2 Trial of GFH018 and Toripalimab in Combination With Concurrent Chemoradiotherapy for Patients With Unresectable, Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC) [NCT05386888]Phase 265 participants (Actual)Interventional2022-09-09Active, not recruiting
Refining Adjuvant Treatment IN Endometrial Cancer Based On Molecular Features: the p53abn-RED Trial, the MMRd-GREEN Trial, the NSMP-ORANGE Trial and the POLEmut-BLUE Trial [NCT05255653]Phase 2/Phase 31,615 participants (Anticipated)Interventional2021-11-11Recruiting
A Multicenter, Open Label, Randomized Study of AMG 951 in Subjects With Previously Untreated Stage IIIb/IV Non-Small Cell Lung Cancer (NSCLC) Treated With Chemotherapy With or Without Bevacizumab [NCT00508625]Phase 2213 participants (Actual)Interventional2006-06-30Completed
A Single-arm，Single-center，Phase II Trial of Camrelizumab Combined With Neoadjuvant Concurrent Chemoradiotherapy for Resectable Locally Advanced Esophageal Squamous Cell Carcinoma（NICE-RT） [NCT05650216]Phase 250 participants (Anticipated)Interventional2022-12-25Not yet recruiting
[NCT00057473]Phase 20 participants Interventional2003-02-28Completed
High-Dose Chemoradiotherapy With Stem Cell Support in Patients With Relapsed or Refractory Hodgkin's Disease [NCT00004169]Phase 20 participants Interventional1993-11-30Completed
Clinical Study of Neoadjuvant Chemotherapy and Immunotherapy Combined With Probiotics in Patients With Potential/Resectable Non-small Cell Lung Cancer [NCT04699721]Phase 140 participants (Anticipated)Interventional2020-07-01Active, not recruiting
High-Risk Neuroblastoma Study 2 of SIOP-Europa-Neuroblastoma (SIOPEN) [NCT04221035]Phase 3800 participants (Anticipated)Interventional2019-11-05Recruiting
A Phase 1, Open-label, Multicenter, Safety Study of Nivolumab (Bms-936558) in Combination With Nab-pacitaxel Plus or Minus Gemcitabine in Pancreatic Cancer, Nab-paclitaxel/Carboplatin in Stage Iiib/iv Non-small Cell Lung Cancer or Nab-paclitaxel in Metast [NCT02309177]Phase 1114 participants (Actual)Interventional2015-01-12Completed
Phase II Trial of Sintilimab, an Anti-PD-1 Monoclonal Antibody, in Combination With Reduction of Cycles of Chemotherapy, as a Novel Neoadjuvant Pre-Surgical Therapy for Oral Cavity or Oropharyngeal Squamous Cell Carcinoma [NCT05098119]Phase 243 participants (Anticipated)Interventional2021-09-16Recruiting
Phase III Study of Concurrent Radiotherapy in Elderly Patients With Esophageal Squamous Cell Carcinoma (ESO-Shanghai 15) [NCT04519905]320 participants (Anticipated)Interventional2020-01-06Recruiting
The Efficacy of Whole-ventricle Irradiation Plus Primary Boost in Patients With Localized Basal Ganglia Germ Cell Tumors: Prospective Phase II Study [NCT05124951]Phase 2150 participants (Anticipated)Interventional2021-09-15Recruiting
SJiMB21: Phase 2 Study of Molecular and Clinical Risk-Directed Therapy for Infants and Young Children With Newly Diagnosed Medulloblastoma [NCT05535166]Phase 2120 participants (Anticipated)Interventional2022-12-20Recruiting
Multicenter, Open-label, ph 2 Study of Carboplatin Plus Mirvetuximab Soravtansine Followed by Mirvetuximab Soravtansine Continuation in FRα Positive, Recurrent Platinum-sensitive, High-grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancer [NCT05456685]Phase 2114 participants (Anticipated)Interventional2022-09-28Recruiting
Phase I/IB Safety and Pharmacodynamic Study of Neoadjuvant (NACT) Paclitaxel and Carboplatin With Ipatasertib as Initial Therapy of Ovarian Cancer PTMA 100805 [NCT05276973]Phase 124 participants (Anticipated)Interventional2022-09-08Recruiting
An Open-label Phase II Trial Evaluating the Efficacy and Safety of Sintilimab Plus Anlotinib Combined With Chemotherapy as Neoadjuvant Therapy in Early-stage Triple-negative Breast Cancer（NeoSACT） [NCT04877821]Phase 231 participants (Anticipated)Interventional2021-09-15Recruiting
Neoadjuvant TCHP Versus THP in Patients With Human Epidermal Growth Factor Receptor 2-positive Breast Cancer (neoCARHP) : a Randomized, Open-label, Multicenter, Phase III Trial [NCT04858529]Phase 3774 participants (Anticipated)Interventional2021-04-30Recruiting
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab (Anti-Tigit Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer [NCT04256421]Phase 3490 participants (Actual)Interventional2020-02-04Active, not recruiting
FIGO 2018 Stage IB2 (> 2 to ≤4cm) Cervical Cancer Treated With Neoadjuvant Chemotherapy Followed by Fertility Sparing Surgery (CoNteSSa) / Neo-Adjuvant Chemotherapy and Conservative Surgery in Cervical Cancer to Preserve Fertility [NCT04016389]90 participants (Anticipated)Interventional2020-02-11Recruiting
DURVA+ : Evaluation of the Safety and Pharmacodynamics of Anti-PD-L1 Antibody Durvalumab in Combination With Chemotherapy in Patients With Advanced Solid Tumors [NCT03907475]Phase 2115 participants (Anticipated)Interventional2019-07-16Recruiting
A Phase 1/2a/3 Evaluation of the Safety and Efficacy of Adding AL3818 (Anlotinib, INN: Catequentinib), a Dual Receptor Tyrosine Kinase Inhibitor, to Standard Platinum-Based Chemotherapy in Subjects With Recurrent or Metastatic Endometrial, Ovarian, Fallop [NCT02584478]Phase 3294 participants (Actual)Interventional2015-12-31Active, not recruiting
A Phase II Trial of AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer [NCT02513563]Phase 242 participants (Actual)Interventional2015-10-30Active, not recruiting
An Early Phase 1 Study of ABT-888 in Combination With Carboplatin and Paclitaxel in Patients With Hepatic or Renal Dysfunction and Solid Tumors [NCT01366144]Phase 194 participants (Actual)Interventional2011-06-20Active, not recruiting
Vorinostat and Carboplatin or Vorinostat and Paclitaxel in Patients With Advanced Solid Tumors: A Pharmacokinetic and Pharmacodynamic Study [NCT01281176]Phase 120 participants (Actual)Interventional2011-02-09Active, not recruiting
A Phase I Study of ABT-888 in Combination With Topotecan Plus Carboplatin for High-Risk Myeloproliferative Disorders and AML Out of Myeloproliferative Disorders [NCT00588991]Phase 112 participants (Actual)Interventional2007-11-28Active, not recruiting
Multicenter, Prospective Observational Study for Early Diagnosis, and Development of Follow-up Protocol and Hearing Rehabilitation Program for Ototoxic Hearing Loss After Chemotherapy for Pediatric Solid Cancer [NCT05633719]300 participants (Anticipated)Observational [Patient Registry]2022-12-01Not yet recruiting
Phase II Single Arm Study of Combination Pembrolizumab, Chemotherapy and Bevacizumab in Patients With Recurrent, Persistent, or Metastatic Cervical Cancer [NCT03367871]Phase 217 participants (Actual)Interventional2018-09-06Terminated(stopped due to Investigator left institution)
Randomized Phase II Trial Contrasting Weekly Paclitaxel, Carboplatin and Cetuximab (PCC) With Cetuximab, Docetaxel, Cisplatin and Fluorouracil (C-TPF) in Previously Untreated Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT01154920]Phase 2128 participants (Anticipated)Interventional2010-07-09Active, not recruiting
Study Comparing the Efficacy and Safety of Epirubicin Combined With Cyclophosphamide Followed by Docetaxel (EC-T) Verses Paclitaxel Combined With Carboplatin (PCb) in the Adjuvant Chemotherapy of Non-triple Negative Breast Cancer [NCT04193059]Phase 31,560 participants (Anticipated)Interventional2018-08-01Recruiting
A Phase II, Single-Arm, Prospective Study of Neoadjuvant Icotinib With Chemotherapy for the Treatment of Patients With Epidermal Growth Factor Receptor Mutation Positive, Resectable for Stage II to IIIB(N2) Non-small Cell Lung Cancer [NCT05104788]Phase 227 participants (Anticipated)Interventional2021-10-25Recruiting
A Randomized, Double-Blind, Multicenter, Phase Ib/III Clinical Study on PD-L1 Monoclonal Antibody SHR-1316 or Placebo in Combination With Chemotherapy as Perioperative Treatment of Resectable Stage II or III Non-Small Cell Lung Cancer [NCT04316364]Phase 3537 participants (Anticipated)Interventional2020-07-14Recruiting
Chidamide Plus Etoposide and Cisplatin/Carboplatin as First-line Treatment for Advanced Extrapulmonary Neuroendocrine Carcinoma: a Prospective, Multicenter, Single-arm, Phase 2 Clinical Study [NCT05076786]Phase 228 participants (Anticipated)Interventional2021-10-27Recruiting
Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in First-line Treatment for Patients With Metastatic Lung Adenocarcinoma: A Randomized Phase III Study [NCT04339218]Phase 3214 participants (Anticipated)Interventional2020-08-28Recruiting
Phase III International, Randomized Study of Trabectedin Plus Pegylated Liposomal Doxorubicin (PLD) Versus Carboplatin Plus PLD in Patients With Ovarian Cancer Progressing Within 6-12 Months of Last Platinum [NCT01379989]Phase 3617 participants (Actual)Interventional2011-06-30Completed
A Randomized, Multicenter, Open-Label, Two-Arm, Phase III Neoadjuvant Study Evaluating Trastuzumab Emtansine Plus Pertuzumab Compared With Chemotherapy Plus Trastuzumab and Pertuzumab for Patients With HER2-Positive Breast Cancer [NCT02131064]Phase 3444 participants (Actual)Interventional2014-06-25Completed
LCCC 1330 - A Phase II Study of Weekly Carboplatin, Paclitaxel and Cetuximab for Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT02124707]Phase 214 participants (Actual)Interventional2014-06-16Completed
Safety and Efficacy of Nab-paclitaxel (Abraxane) in Combination With Carboplatin as First Line Treatment in Elderly Subjects With Advance Non-Small Cell Lung Cancer (NSCLC): A Phase IV, Randomized, Open-Label, Multicenter Study (Abound.70+) [NCT02151149]Phase 4143 participants (Actual)Interventional2014-06-09Completed
An Open Label, Multicenter, Phase Ib/II Study of SHR-1802 in Combination With Adebrelimab in Patients With Advanced Solid Tumors [NCT05794477]Phase 1/Phase 2132 participants (Anticipated)Interventional2023-04-28Recruiting
A Randomized, Double-blind, Phase 3 Study Evaluating the Efficacy and Safety of ABP 215 Compared With Bevacizumab in Subjects With Advanced Non-Small Cell Lung Cancer [NCT01966003]Phase 3642 participants (Actual)Interventional2013-11-11Completed
Phase 1b/2, Multicenter, Open-label Study of Carfilzomib, Carboplatin, and Etoposide in Subjects With Previously Untreated Extensive-stage Small-cell Lung Cancer [NCT01987232]Phase 1/Phase 232 participants (Actual)Interventional2013-11-05Completed
A Phase III, Open-label, Randomised Study of Datopotamab Deruxtecan (Dato-DXd) With or Without Durvalumab Compared With Investigator's Choice of Chemotherapy (Paclitaxel, Nab-paclitaxel or Gemcitabine + Carboplatin) in Combination With Pembrolizumab in Pa [NCT06103864]Phase 3625 participants (Anticipated)Interventional2023-11-23Recruiting
A Prospective, Multi-cohort, Exploratory Phase II Study of Trilaciclib Combined With Standard Chemotherapy in The Adjuvant Treatment of Hormone Receptor (HR) Negative Breast Cancer [NCT05978648]Phase 2116 participants (Anticipated)Interventional2023-09-20Recruiting
A Phase III, Randomised, Double-Blind, Placebo-Controlled, Multicentre Study Of The Efficacy And Safety Of Atezolizumab Plus Chemotherapy For Patients With Early Relapsing Recurrent (Inoperable Locally Advanced Or Metastatic) Triple-Negative Breast Cancer [NCT03371017]Phase 3572 participants (Anticipated)Interventional2018-01-11Active, not recruiting
An Open Label Randomized Phase 2, Pilot Study to Investigate the Effectiveness of Palliative Chemotherapy in Stage IVB, Recurrent or Persistent Carcinoma Cervix [NCT02492503]Phase 1/Phase 240 participants (Anticipated)Interventional2013-11-30Active, not recruiting
Predictive Biomarker for the Efficacy and Safety of the Combination of Chemotherapy and Tislelizumab in Non Small Cell Lung Cancer：a Multicentre Prospective Clinical Trial [NCT05244837]Phase 2100 participants (Anticipated)Interventional2020-12-22Recruiting
PERSONALIZED MEDICINE GROUP / UCBG UC-0105/1304: SAFIR02_Breast - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Breast Cancer [NCT02299999]Phase 21,460 participants (Actual)Interventional2014-04-07Active, not recruiting
Modulation of the Expression of Papillomavirus (HPV) Oncoproteins to Major the Radiosensitivity: Phase I Trial Combining an Antiviral Agent VISTIDE and Radiochemotherapy in Cervical Cancers [NCT02515877]Phase 115 participants (Actual)Interventional2008-01-31Completed
Chinese PLA Generation Hospital [NCT03095001]Phase 270 participants (Anticipated)Interventional2017-06-01Recruiting
A Phase II Study of Lenvatinib (E7080/MK-7902) in Combination With Carboplatin Pemetrexed and Pembrolizumab (MK-3475) for Patients With Pretreated Advanced Non-squamous Non-small Cell Lung Cancer Harboring EGFR Mutations [NCT05258279]Phase 230 participants (Anticipated)Interventional2022-07-01Active, not recruiting
A Phase 1 Study of Entinostat in Combination With Atezolizumab / Carboplatin / Etoposide in Previously Untreated Extensive-Stage Small Cell Lung Cancer [NCT04631029]Phase 13 participants (Actual)Interventional2021-04-27Completed
A Phase 2 Study of Pevonedistat in Combination With Carboplatin and Paclitaxel in Advanced Intrahepatic Cholangiocarcinoma [NCT04175912]Phase 252 participants (Anticipated)Interventional2020-03-16Active, not recruiting
Improved Breast Cancer Therapy (I-BCT-1) in the Neoadjuvant and Metastatic Setting: A Phase 2 Clinical Trial Protocol Studying Biological Rationale for the Optimal Selection of Treatment Regimens [NCT02546232]Phase 2196 participants (Actual)Interventional2015-04-01Active, not recruiting
Matched Paired Pharmacodynamics and Feasibility Study of Pembrolizumab in Combination With Chemotherapy in Frontline Ovarian Cancer [NCT02520154]Phase 231 participants (Actual)Interventional2016-07-05Active, not recruiting
A Phase II Open Label Randomised Comparative Multicentre Study to Compare the Efficacy and Tolerability of Olaparib in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone in Patients With Platinum Sensitive Advanced Serous [NCT01081951]Phase 2162 participants (Actual)Interventional2010-02-04Active, not recruiting
Phase III Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy With or Without Adjuvant Chemotherapy in High-Risk Patients With Early-Stage Cervical Carcinoma Following Radical Hysterectomy [NCT00980954]Phase 3238 participants (Actual)Interventional2009-09-30Active, not recruiting
A Open-label, Single Center, Phase II Study of Surufatinib Combined With Toripalimab and Chemotherapy in Patients With Advanced Non-squamous Non-small-cell Lung Cancer [NCT05003037]Phase 2106 participants (Anticipated)Interventional2021-12-08Recruiting
A Randomized Phase II Study of Single Agent Erlotinib [Tarceva (TM), OSI-774] Versus Standard Chemotherapy in Patients With Previously Untreated Advanced NSCLC and a Poor Performance Status [NCT00085839]Phase 2103 participants (Actual)Interventional2004-02-29Completed
Phase II Study of Tandem Cycle Dose-Intense Chemotherapy of Melphalan and Carboplatin, Thiotepa and Cyclophosphamide (STMP V) ± Trastuzumab Followed by Helical Tomotherapy or Local Regional Radiation Therapy for Stage IV Metastatic and Stage IIIB/C Breast [NCT00182793]Phase 232 participants (Actual)Interventional2005-07-31Completed
The Quarterback Trial: A Randomized Phase III Clinical Trial Comparing Reduced and Standard Radiation Therapy Doses for Locally Advanced HPV Positive Oropharynx Cancer [NCT01706939]Phase 323 participants (Actual)Interventional2012-09-01Active, not recruiting
Drug Treatment Patterns and Effects for Metastatic Non-small Cell Lung Cancer Patients In NORway (DELINOR) [NCT05834348]20,605 participants (Anticipated)Observational2023-06-26Recruiting
A Prospective, Single-armed Study to Evaluate the Efficacy and Safety of Neoadjuvant Pembrolizumab Plus Chemotherapy in Resectable Locally Advanced Esophageal Squamous Cell Carcinoma Patients [NCT05302011]Phase 228 participants (Actual)Interventional2020-06-01Completed
A Phase 1 Study of Palbociclib in Combination With Cisplatin or Carboplatin in Advanced Solid Malignancies [NCT02897375]Phase 171 participants (Actual)Interventional2016-10-24Completed
Phase II Study of Dose Dense Carboplatin and Taxotere With Herceptin As Primary Systemic Therapy in Breast Cancer [NCT00232479]Phase 248 participants (Actual)Interventional2005-09-30Completed
Phase III Study to Evaluate the Optimal Timing of Postoperative Radiotherapy for High Risk of Locoregional Recurrence Patients With Completely Resected Stage IIIA(N2) Non-Small Cell Lung Cancer [NCT02974426]Phase 31,094 participants (Anticipated)Interventional2016-11-30Recruiting
A Phase I Followed by a Randomized Phase II Trial of Two Cycles Carboplatin-Olaparib Followed by Olaparib Monotherapy Versus Capecitabine in BRCA-1 or -2 Mutated Her2 Negative Advanced Breast Cancer as First Line Treatment [NCT02418624]Phase 125 participants (Actual)Interventional2015-05-31Completed
BELOVA: A Non-Interventional Study to Collect Data on the Safety and Efficacy of Frontline Bevacizumab Treatment in Ovarian Cancer Patients 70 Years and Older [NCT02393898]76 participants (Actual)Observational2015-04-23Completed
A Randomized Phase II Study of Metformin Plus Paclitaxel/Carboplatin/Bevacizumab in Patients With Previously Untreated Advanced/Metastatic Pulmonary Adenocarcinoma [NCT01578551]Phase 225 participants (Actual)Interventional2012-05-31Terminated(stopped due to Low enrollment)
ATP7A Transporter as Biomarker for Predicting Chemoresistance of Serous Ovarian Cancer [NCT05490407]30 participants (Anticipated)Interventional2021-03-17Recruiting
FurmOnertinib Mesylate With or Without Chemotherapy +/- bevacizUmab as firSt Line Treatment in Advanced Non-small Cell Lung Cancer Patients With Uncleared Epidermal Growth Factor Receptor (EGFR) Mutation Positive Circulating Tumor Cell DNA [NCT05334277]Phase 2280 participants (Anticipated)Interventional2022-05-06Recruiting
A Phase III, Open-Label, Randomized Study of Atezolizumab (Anti-PD-L1 Antibody) Compared With Gemcitabine+Cisplatin or Carboplatin for PD-L1-Selected, Chemotherapy Naive Patients With Stage IV Squamous Non-Small Cell Lung Cancer [NCT02409355]Phase 38 participants (Actual)Interventional2015-05-07Terminated(stopped due to The study was closed due to low patient enrollment and the Sponsor's decision to include patients with squamous NSCLC into the GO29431 study, NCT02409342.)
An Open Label, Two Arm Phase II Study of Toripalimab Versus Toripalimab in Combination With Carboplatin and Nab-paclitaxel as a Novel Neoadjuvant Pre-Surgical Therapy for HNSCC [NCT04807140]Phase 257 participants (Anticipated)Interventional2021-07-08Recruiting
A Phase II Multicenter, Open-Label, Single Arm Study to Determine the Efficacy, Safety and Tolerability of AZD2811 and Durvalumab Combination as Maintenance Therapy After Induction With Platinum-Based Chemotherapy Combined With Durvalumab, for the First-L [NCT04745689]Phase 231 participants (Actual)Interventional2021-02-23Active, not recruiting
A Randomized Open-Label Phase 3 Trial of BMS-936558 (Nivolumab) Versus Investigator's Choice in Advanced (Unresectable or Metastatic) Melanoma Patients Progressing Post Anti-CTLA-4 Therapy [NCT01721746]Phase 3405 participants (Actual)Interventional2012-12-21Completed
A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-S [NCT02264990]Phase 3595 participants (Actual)Interventional2014-09-30Completed
A Randomized, Open-Label, Phase 3 Study of Cosibelimab (CK-301) in Combination With Platinum+Pemetrexed Chemotherapy in Subjects With First-Line Metastatic Non-squamous Non-Small Cell Lung Cancer [NCT04786964]Phase 325 participants (Actual)Interventional2021-12-08Terminated(stopped due to Regional political conflict)
PHASE 3, RANDOMIZED, OPEN-LABEL STUDY OF THE EFFICACY AND SAFETY OF CRIZOTINIB VERSUS PEMETREXED/CISPLATIN OR PEMETREXED/CARBOPLATIN IN PREVIOUSLY UNTREATED EAST ASIAN PATIENTS WITH NON-SQUAMOUS CARCINOMA OF THE LUNG HARBORING A TRANSLOCATION OR INVERSION [NCT01639001]Phase 3207 participants (Actual)Interventional2012-09-29Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00002558 (1) [back to overview]Overall Objective Response
NCT00002931 (3) [back to overview]Toxic Effects
NCT00002931 (3) [back to overview]Progression-free Survival
NCT00002931 (3) [back to overview]Overall Survival
NCT00003631 (1) [back to overview]Objective Response
NCT00003644 (3) [back to overview]Number of Participants With Adverse Events Grade 3 or Greater
NCT00003644 (3) [back to overview]Progression-free Survival
NCT00003644 (3) [back to overview]Overall Survival
NCT00003816 (4) [back to overview]4 Year PFS
NCT00003816 (4) [back to overview]4 yr OS
NCT00003816 (4) [back to overview]CR Rate
NCT00003816 (4) [back to overview]Toxicity/TRM at Day 100
NCT00004092 (2) [back to overview]Five-Year Overall Survival
NCT00004092 (2) [back to overview]Five-Year Relapse-free Survival
NCT00004859 (3) [back to overview]Overall Survival Time
NCT00004859 (3) [back to overview]Response Rate at Best Response to Treatment
NCT00004859 (3) [back to overview]Time to Disease Progression
NCT00008138 (2) [back to overview]Progression-Free Survival
NCT00008138 (2) [back to overview]Overall Survival
NCT00010257 (2) [back to overview]Best Overall Response by RECIST Criteria (Version 1.0)
NCT00010257 (2) [back to overview]Duration of Response
NCT00011986 (3) [back to overview]Number of Participants With Observed Adverse Effects (Grade 3 and Above) Assessed by Common Toxicity Criteria Version 2.0
NCT00011986 (3) [back to overview]Progression-free Survival
NCT00011986 (3) [back to overview]Overall Survival
NCT00016913 (3) [back to overview]Toxicity
NCT00016913 (3) [back to overview]Time to Prostate-specific Antigen Failure
NCT00016913 (3) [back to overview]Progression-free Survival (PFS)
NCT00021255 (3) [back to overview]Overall Survival- Percentage of Participants Who Survived at 10 Years
NCT00021255 (3) [back to overview]Percentage of Participants With Disease Free Survival at 10 Years
NCT00021255 (3) [back to overview]Percentage of Participants With Disease Free Survival at 5 Years
NCT00023673 (6) [back to overview]Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level)
NCT00023673 (6) [back to overview]Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy
NCT00023673 (6) [back to overview]Number of Patients With Complete Response at 3 Months After Completion of Therapy
NCT00023673 (6) [back to overview]Percentage of Patients Who Survive at Least 12 Months
NCT00023673 (6) [back to overview]Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities.
NCT00023673 (6) [back to overview]Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level)
NCT00027846 (6) [back to overview]Event-free Survival
NCT00027846 (6) [back to overview]Event-free Survival (EFS)
NCT00027846 (6) [back to overview]Event-free Survival (EFS)
NCT00027846 (6) [back to overview]Overall Survival
NCT00027846 (6) [back to overview]Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy
NCT00027846 (6) [back to overview]Local Control and Patterns of Failure
NCT00039195 (1) [back to overview]Progression Free Survival
NCT00043108 (5) [back to overview]Complete Resection Rates
NCT00043108 (5) [back to overview]Event-free Survival
NCT00043108 (5) [back to overview]Pathologic Complete Remission (pCR)
NCT00043108 (5) [back to overview]Survival
NCT00043108 (5) [back to overview]Toxic Death Rate
NCT00045630 (3) [back to overview]Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug
NCT00045630 (3) [back to overview]Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy
NCT00045630 (3) [back to overview]Overall Survival (OS)
NCT00047320 (6) [back to overview]Overall Survival (OS)
NCT00047320 (6) [back to overview]The Probability of Event-free Survival (EFS)
NCT00047320 (6) [back to overview]Progression-free Survival (PFS)
NCT00047320 (6) [back to overview]Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity
NCT00047320 (6) [back to overview]Number of Patients Experiencing Toxic Death
NCT00047320 (6) [back to overview]Response to Induction Chemotherapy
NCT00049257 (4) [back to overview]Objective Response Rate
NCT00049257 (4) [back to overview]Overall Survival Rate
NCT00049257 (4) [back to overview]Prostate-specific Antigen (PSA) Response Rate
NCT00049257 (4) [back to overview]Time to PSA Progression
NCT00050960 (1) [back to overview]Overall Survival
NCT00059787 (5) [back to overview]To Measure EGFR Gene Amplification in Tumor Specimens
NCT00059787 (5) [back to overview]Pathologic Complete Response Rates
NCT00059787 (5) [back to overview]To Determine Progession Free Survival With the Addition of OSI-774 (Tarceva) to the Combination of Paclitaxel and Carboplatin
NCT00059787 (5) [back to overview]The Percentage of Participants Experiencing Toxicty (Grade 2 and Grade 3/4) Associated With the Combined Regimen
NCT00059787 (5) [back to overview]To Determine the Tolerability of Twelve Months of Maintenance Treatment
NCT00063258 (1) [back to overview]Number of Patients With Response
NCT00063999 (3) [back to overview]Number of Participants With Indicated Severity of CTCAE v2 Graded Neurotoxicity and Infection
NCT00063999 (3) [back to overview]Patient-reported Neurotoxicity (Ntx) as Measured by the FACT/GOG-Ntx Subscale (Short)
NCT00063999 (3) [back to overview]Patient Reported Quality of Life as Measured With the Combination of Physical Well-being (PWB) Subscale and Functional Well-being (FWB) Subscale From the FACT-G
NCT00068341 (5) [back to overview]Pathologic Nodal Status
NCT00068341 (5) [back to overview]Tumor Response Assessment
NCT00068341 (5) [back to overview]Clinical Tumor Response by Physical Exam and Imaging Studies
NCT00068341 (5) [back to overview]Clinico-histologic Predictors of pCR (Pathologic Complete Response)
NCT00068341 (5) [back to overview]Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively.
NCT00072384 (6) [back to overview]Group C Eyes - Treatment Failure Within One Year
NCT00072384 (6) [back to overview]Group D Eyes - Treatment Failure Within One Year
NCT00072384 (6) [back to overview]Event-free Survival (EFS)
NCT00072384 (6) [back to overview]Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement
NCT00072384 (6) [back to overview]Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence
NCT00072384 (6) [back to overview]Toxicity Associated With Chemotherapy
NCT00072514 (4) [back to overview]Peripheral Blood Stem Cell Collection
NCT00072514 (4) [back to overview]Overall and Complete Response Rates
NCT00072514 (4) [back to overview]Hematologic and Non-hematologic Adverse Events.
NCT00072514 (4) [back to overview]Ability to Successfully Deliver the Investigational Therapy Without Incurring the Protocol Suspension Rules
NCT00074165 (1) [back to overview]Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years.
NCT00077207 (6) [back to overview]Number of Participants Who Experienced Toxic Death
NCT00077207 (6) [back to overview]Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia.
NCT00077207 (6) [back to overview]Long Term Feasibility Success
NCT00077207 (6) [back to overview]Short Term Feasibility Success
NCT00077207 (6) [back to overview]Percentage Probability of Event-free Survival (EFS)
NCT00077207 (6) [back to overview]Percent Probability of Progression-free Survival (PFS)
NCT00077376 (8) [back to overview]Time to Disease Progression for HER2+ Patients
NCT00077376 (8) [back to overview]Time to Treatment Failure for All Treated Patients
NCT00077376 (8) [back to overview]Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study)
NCT00077376 (8) [back to overview]Time to Treatment Failure for HER2+ Patients
NCT00077376 (8) [back to overview]Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study)
NCT00077376 (8) [back to overview]Kaplan-Meier Estimate of Overall Survival at 3 Years for All Treated Patients
NCT00077376 (8) [back to overview]Time to Disease Progression for All Treated Patients
NCT00077376 (8) [back to overview]Kaplan-Meier Estimate of Overall Survival at 3 Years for HER2+ Patients
NCT00079417 (5) [back to overview]Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level
NCT00079417 (5) [back to overview]Event-free Survival
NCT00079417 (5) [back to overview]Response Rate (RR) at Eye Levels After the First Course of Therapy
NCT00079417 (5) [back to overview]Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
NCT00079417 (5) [back to overview]Response Rate (RR) at Patient Level After the First Course of Therapy
NCT00085098 (4) [back to overview]Number of Participants With a Response to Regimen B
NCT00085098 (4) [back to overview]Event-free Survival
NCT00085098 (4) [back to overview]Quality of Life (QOL) and Neurocognitive Assessment (NP)
NCT00085098 (4) [back to overview]Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
NCT00085839 (3) [back to overview]Overall Survival
NCT00085839 (3) [back to overview]Progression-free Survival
NCT00085839 (3) [back to overview]Best Tumor Response
NCT00089297 (4) [back to overview]Proportion of Patients With Objective Response by RECIST
NCT00089297 (4) [back to overview]Progression-free Survival
NCT00089297 (4) [back to overview]Overall Survival
NCT00089297 (4) [back to overview]Event-free Survival Rate at 1 Year
NCT00090610 (5) [back to overview]Progression-free Survival (PFS)
NCT00090610 (5) [back to overview]Objective Response Rate
NCT00090610 (5) [back to overview]Median Overall Survival
NCT00090610 (5) [back to overview]Recurrence-Free Survival
NCT00090610 (5) [back to overview]Quality of Life
NCT00093145 (6) [back to overview]Time to Disease Progression
NCT00093145 (6) [back to overview]Percentage of Participants With a Total Response
NCT00093145 (6) [back to overview]Percentage of Participants Who Achieved an Objective Confirmed Complete or Partial Overall Response
NCT00093145 (6) [back to overview]Duration of Response
NCT00093145 (6) [back to overview]Overall Patient Survival
NCT00093145 (6) [back to overview]Number of Participants With Adverse Events (AEs)
NCT00093756 (5) [back to overview]The Primary Endpoint of This Trial is the Proportion of Patients Alive at 1 Year. Phase II Patients Only.
NCT00093756 (5) [back to overview]Confirmed Tumor Response
NCT00093756 (5) [back to overview]Frequency and Severity of Observed Toxicity, Graded by Common Terminology Criteria for Adverse Events (CTCAE)
NCT00093756 (5) [back to overview]Overall Survival
NCT00093756 (5) [back to overview]Progression-free Survival
NCT00094835 (11) [back to overview]Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2
NCT00094835 (11) [back to overview]Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2
NCT00094835 (11) [back to overview]Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1
NCT00094835 (11) [back to overview]Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2
NCT00094835 (11) [back to overview]Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1
NCT00094835 (11) [back to overview]Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1
NCT00094835 (11) [back to overview]Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2
NCT00094835 (11) [back to overview]Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1
NCT00094835 (11) [back to overview]Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2
NCT00094835 (11) [back to overview]Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1
NCT00094835 (11) [back to overview]Percentage of Participants With an Overall Objective Response
NCT00094861 (8) [back to overview]Duration of Grade 2 or Higher Dysphagia
NCT00094861 (8) [back to overview]Number of Participants With Unplanned Breaks in Radiotherapy
NCT00094861 (8) [back to overview]Number of Participants With Severe (Grade 3 or Higher) Dysphagia
NCT00094861 (8) [back to overview]Number of Participants With Grade 2 or Higher Dysphagia
NCT00094861 (8) [back to overview]Number of Participants Hospitalized
NCT00094861 (8) [back to overview]Maximal Eastern Cooperative Oncology Group (ECOG) Performance Status Increase
NCT00094861 (8) [back to overview]Maximal Dysphagia Grade
NCT00094861 (8) [back to overview]Maximal Body Weight Loss
NCT00095875 (2) [back to overview]Progression-free Survival and Disease-specific Survival as Assessed by Disease Progression or Death and Log Rank Tests at the Median, and 2, 3, and 5 Years
NCT00095875 (2) [back to overview]Overall Survival
NCT00096200 (3) [back to overview]Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
NCT00096200 (3) [back to overview]Evaluate the Progression-free Survival Rate
NCT00096200 (3) [back to overview]Overall Survival
NCT00096226 (8) [back to overview]Distribution of R0, R1, and R2 Resections After Chemotherapy
NCT00096226 (8) [back to overview]Distribution of Highest Grade Adverse Event
NCT00096226 (8) [back to overview]Progression-free Survival at Two Years
NCT00096226 (8) [back to overview]Percentage of Patients With Complete Pathological Response After Concurrent Chemotherapy and Radiation Therapy
NCT00096226 (8) [back to overview]Percentage of Patients Able to Undergo Surgical Resection
NCT00096226 (8) [back to overview]Overall Survival at Two Years
NCT00096226 (8) [back to overview]Mediastinal Nodal Clearance Rate
NCT00096226 (8) [back to overview]Percentage of Patients With Major Surgical Morbidities Within 30 Days of Surgery
NCT00101283 (3) [back to overview]Best Overall Response by RECIST Criteria (Version 1.0)
NCT00101283 (3) [back to overview]Progression-Free Survival
NCT00101283 (3) [back to overview]Overall Survival
NCT00110019 (3) [back to overview]Overall Survival
NCT00110019 (3) [back to overview]Progression-free Survival
NCT00110019 (3) [back to overview]Objective Response (Complete and Partial Response) Rate
NCT00111007 (5) [back to overview]Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted
NCT00111007 (5) [back to overview]Overall Survival (OS)
NCT00111007 (5) [back to overview]Progression Free Survival (PFS)
NCT00111007 (5) [back to overview]Duration of Response (DOR)
NCT00111007 (5) [back to overview]Time to Progression (TTP)
NCT00112294 (15) [back to overview]Median Number of Months of Response
NCT00112294 (15) [back to overview]Median Number of Months of Survival
NCT00112294 (15) [back to overview]Number of Participants Experiencing Other Significant AEs: Acneform Rash
NCT00112294 (15) [back to overview]Number of Participants Experiencing Other Significant AEs: Cardiac AEs
NCT00112294 (15) [back to overview]Number of Participants With Improvement of Symptoms
NCT00112294 (15) [back to overview]Number of Participants Who Exprienced the Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=5% Participants
NCT00112294 (15) [back to overview]Number of Participants Who Experienced the Most Frequent Grade 3-4 Serum Chemistry Abnormalities Occurring in >=5% Participants
NCT00112294 (15) [back to overview]Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD)
NCT00112294 (15) [back to overview]Number of Participants Who Died, or Experienced Other Serious Adverse Events (SAEs) and Adverse Events (AEs)
NCT00112294 (15) [back to overview]Number of Participants Experiencing AEs Leading to Study Drug Discontinuation
NCT00112294 (15) [back to overview]Median Change From Baseline in Symptoms, by Time Point
NCT00112294 (15) [back to overview]Median Number of Months to Response
NCT00112294 (15) [back to overview]Number of Participants With Complete Response (CR) or Partial Response (PR)
NCT00112294 (15) [back to overview]Median Number of Months of Progression-free Survival (PFS)
NCT00112294 (15) [back to overview]Number of Participants Experiencing Other Significant AEs: Infusion Reaction
NCT00112489 (2) [back to overview]Response Evaluation Criteria in Solid Tumors Criteria (RECIST) 1.0 Best Response
NCT00112489 (2) [back to overview]Nature and Degree of Toxicity
NCT00113516 (35) [back to overview]Dose-Corrected Ctrough of SU-012662 (Sunitinib's Metabolite)
NCT00113516 (35) [back to overview]Ctrough of Total Drug (Sunitinib + SU-012662)
NCT00113516 (35) [back to overview]Ctrough of SU-012662 (Sunitinib's Metabolite)
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline Changes From Baseline
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline Changes From Baseline
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline
NCT00113516 (35) [back to overview]Change From Baseline in HRQOL and Lung Cancer Related Symptoms as Assessed With the EORTC QLQ Lung Cancer Module (QLQ-LC13)
NCT00113516 (35) [back to overview]Change From Baseline in Health Related Quality of Life (HRQOL) and Lung Cancer Related Symptoms as Assessed With the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (EORTC QLQ-C30)
NCT00113516 (35) [back to overview]VEGF-C Concentration at Baseline
NCT00113516 (35) [back to overview]Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Concentration at Baseline
NCT00113516 (35) [back to overview]Time to Tumor Progression (TTP)
NCT00113516 (35) [back to overview]Soluble E-Selectin at Baseline
NCT00113516 (35) [back to overview]Proportion of Subjects Surviving at One Year
NCT00113516 (35) [back to overview]Duration of Response (DR)
NCT00113516 (35) [back to overview]Progression-free Survival (PFS)
NCT00113516 (35) [back to overview]VEGFR3 Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
NCT00113516 (35) [back to overview]Dose-Corrected Ctrough of Sunitinib
NCT00113516 (35) [back to overview]VEGF-C Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
NCT00113516 (35) [back to overview]VEGF-C Ratio to Baseline at Each Time Point
NCT00113516 (35) [back to overview]VEGFR3 Ratio to Baseline at Each Time Point
NCT00113516 (35) [back to overview]VEGFR3 at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline
NCT00113516 (35) [back to overview]Trough Plasma Concentration (Ctrough) of Sunitinib
NCT00113516 (35) [back to overview]Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline
NCT00113516 (35) [back to overview]Soluble E-Selectin Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
NCT00113516 (35) [back to overview]Soluble E-Selectin Ratio to Baseline at Each Time Point
NCT00113516 (35) [back to overview]Soluble E-Selectin at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
NCT00113516 (35) [back to overview]Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)
NCT00113516 (35) [back to overview]Number of Subjects With Overall Confirmed Objective Disease Response
NCT00113516 (35) [back to overview]Overall Survival (OS)
NCT00113516 (35) [back to overview]VEGF-C at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)
NCT00117962 (4) [back to overview]Number of Participants With Overall Tumor Response
NCT00117962 (4) [back to overview]18 Month Survival
NCT00117962 (4) [back to overview]Overall Survival
NCT00117962 (4) [back to overview]Failure-free Survival
NCT00122460 (9) [back to overview]Disease Control
NCT00122460 (9) [back to overview]Duration of Response
NCT00122460 (9) [back to overview]Overall Survival Time (OS)
NCT00122460 (9) [back to overview]Progression-free Survival Time (PFS)
NCT00122460 (9) [back to overview]Safety - Number of Patients Experiencing Any Adverse Event
NCT00122460 (9) [back to overview]Time to Treatment Failure
NCT00122460 (9) [back to overview]Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status
NCT00122460 (9) [back to overview]Quality of Life Assessment (EORTC QLQ-C30) Social Functioning
NCT00122460 (9) [back to overview]Best Overall Response
NCT00126581 (8) [back to overview]Progression Free Survival With KRAS Mutation Status
NCT00126581 (8) [back to overview]18 Weeks Progression Free Survival (PFS) Rate
NCT00126581 (8) [back to overview]Overall Response Rate
NCT00126581 (8) [back to overview]Progression Free Survival (PFS) by Epidermal Growth Factor Receptor (EGFR) Mutation Status
NCT00126581 (8) [back to overview]Overall Response Rate by EGFR Mutation Status
NCT00126581 (8) [back to overview]Overall Survival
NCT00126581 (8) [back to overview]Number of Participants With Grade 3, 4 or 5 Adverse Event at Least Possibly Related to Treatment.
NCT00126581 (8) [back to overview]Overall Response Rate With KRAS Mutational Status
NCT00129727 (3) [back to overview]Toxicity
NCT00129727 (3) [back to overview]Response Rate (RECIST-1)
NCT00129727 (3) [back to overview]PFS
NCT00147225 (2) [back to overview]Number of Participants With Venous Thromboembolism (VTE) Related Serious Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy
NCT00147225 (2) [back to overview]Number of Participants With Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy
NCT00147537 (22) [back to overview]Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b
NCT00147537 (22) [back to overview]Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b
NCT00147537 (22) [back to overview]Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2
NCT00147537 (22) [back to overview]Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b
NCT00147537 (22) [back to overview]Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b
NCT00147537 (22) [back to overview]Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b
NCT00147537 (22) [back to overview]Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b
NCT00147537 (22) [back to overview]CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b
NCT00147537 (22) [back to overview]CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b
NCT00147537 (22) [back to overview]Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b
NCT00147537 (22) [back to overview]Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b
NCT00147537 (22) [back to overview]Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b
NCT00147537 (22) [back to overview]Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b
NCT00147537 (22) [back to overview]Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 1b
NCT00147537 (22) [back to overview]Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2
NCT00147537 (22) [back to overview]Objective Response Rate: Phase 1b
NCT00147537 (22) [back to overview]Objective Response Rate: Phase 2
NCT00147537 (22) [back to overview]Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 1 in Phase 1b
NCT00147537 (22) [back to overview]Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b
NCT00147537 (22) [back to overview]Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b
NCT00147537 (22) [back to overview]Recommended Phase 2 Dose (RP2D): Phase 1b
NCT00147537 (22) [back to overview]Progression-Free Survival (PFS): Phase 2
NCT00148668 (1) [back to overview]Pathological Complete Response After Preoperative Therapy With Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in Patients With HER-2 Positive Early Breast Cancer
NCT00152477 (6) [back to overview]Overall Survival
NCT00152477 (6) [back to overview]Time to Treatment Failure
NCT00152477 (6) [back to overview]Tumor Response Rate (RR)
NCT00152477 (6) [back to overview]Progression Free Survival (PFS)
NCT00152477 (6) [back to overview]Time to Response
NCT00152477 (6) [back to overview]Duration of Overall Response
NCT00176254 (5) [back to overview]Response Rate to Induction Chemotherapy Prior to Definitive Therapy (Surgery or Radiation)
NCT00176254 (5) [back to overview]5 Year Disease-specific Survival
NCT00176254 (5) [back to overview]5 Year Overall Survival Rates
NCT00176254 (5) [back to overview]5 Year Progression Free Survival
NCT00176254 (5) [back to overview]Frequency of Severe (>/= Grade 3) Toxicities
NCT00182793 (2) [back to overview]5-Year Overall Survival Rate
NCT00182793 (2) [back to overview]5-Year Relapse-free Survival Rate
NCT00186888 (27) [back to overview]Ocular Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification
NCT00186888 (27) [back to overview]Ocular Survival of Stratum B Patients Responding to Window Treatment
NCT00186888 (27) [back to overview]Ocular Survival of Stratum A Patients
NCT00186888 (27) [back to overview]Number of Participants With Change in Size of Pineal Gland
NCT00186888 (27) [back to overview]Stratum B Response Rate of Early Stage Eyes to Window Therapy
NCT00186888 (27) [back to overview]Change in Parenting Stress Index (PSI)
NCT00186888 (27) [back to overview]Ocular Survival of Eyes of Stratum B Patients
NCT00186888 (27) [back to overview]Ocular Survival of Eyes in Stratum B Patients Responding to Window Treatment
NCT00186888 (27) [back to overview]Ocular Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification
NCT00186888 (27) [back to overview]Mean Primary Visual Cortex Function: Maximum T-value
NCT00186888 (27) [back to overview]Mean Primary Visual Cortex Function: Cluster Size
NCT00186888 (27) [back to overview]Event-free Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification
NCT00186888 (27) [back to overview]Event-free Survival of Stratum B Patients Responding to Window Treatment
NCT00186888 (27) [back to overview]Event-free Survival of Stratum A Patients
NCT00186888 (27) [back to overview]Event-free Survival of Eyes in Stratum B Patients Responding to Window Treatment
NCT00186888 (27) [back to overview]Event-free Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification
NCT00186888 (27) [back to overview]Change in Relevant Daily Living Skills
NCT00186888 (27) [back to overview]Change in Parent Report of Social-Emotional Factors
NCT00186888 (27) [back to overview]Change in Cognitive Functioning
NCT00186888 (27) [back to overview]Stratum B Response to Window Therapy
NCT00186888 (27) [back to overview]Relationship Between Topotecan Clearance (CL) and ABCG2/B1 Genotype in Stratum B Participants.
NCT00186888 (27) [back to overview]Relationship Between Topotecan Clearance (CL) and CYP3A4/5 Genotype in Stratum B Participants.
NCT00186888 (27) [back to overview]Number of Participants With Development of Pineal Cysts
NCT00186888 (27) [back to overview]Change in Distortion Product Otoacoustic Emissions (DPOAEs)
NCT00186888 (27) [back to overview]Event-free Survival of Eyes of Stratum B Patients
NCT00186888 (27) [back to overview]Assessment of School Readiness
NCT00186888 (27) [back to overview]Number of Patients Recommended for and Utilizing Rehabilitation Services
NCT00191451 (5) [back to overview]Time to Disease Progression (TTP)
NCT00191451 (5) [back to overview]Overall Tumor Response
NCT00191451 (5) [back to overview]Percentage of Patients With Overall Survival at 1 Year and 2 Years
NCT00191451 (5) [back to overview]Duration of Response
NCT00191451 (5) [back to overview]Number of Patients Who Experienced Alopecia
NCT00191646 (4) [back to overview]Time to Treatment Failure
NCT00191646 (4) [back to overview]Proportion of Participants With Response (Response Rate)
NCT00191646 (4) [back to overview]Progression Free Survival (PFS)
NCT00191646 (4) [back to overview]Overall Survival
NCT00191854 (5) [back to overview]Overall Survival
NCT00191854 (5) [back to overview]Progression Free Survival (PFS)
NCT00191854 (5) [back to overview]Best Overall Response
NCT00191854 (5) [back to overview]Number of Participants With a Time to Treatment Failure (TTTF) Event
NCT00191854 (5) [back to overview]Duration of Response
NCT00193375 (3) [back to overview]Number of Grade 3/4 Toxicities Patients Experienced on Maintenance Bevacizumab Following Chemoradiation for Limited Stage - Small Cell Lung Cancer (LS-SCLC)
NCT00193375 (3) [back to overview]Overall Response Rate
NCT00193375 (3) [back to overview]2-Year Progression-free Survival (PFS)
NCT00193427 (4) [back to overview]Pathologic Complete Response Rate
NCT00193427 (4) [back to overview]Progression Free Survival (PFS)
NCT00193427 (4) [back to overview]Overall Survival (OS)
NCT00193427 (4) [back to overview]Overall Response Rate (ORR)
NCT00193596 (2) [back to overview]Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
NCT00193596 (2) [back to overview]Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
NCT00201734 (6) [back to overview]Maximum Tolerated Dose in Phase I Portion of Study
NCT00201734 (6) [back to overview]Phase I: To Determine Side Effects
NCT00201734 (6) [back to overview]Time to Tumor Progression for Patients
NCT00201734 (6) [back to overview]Progression-Free Survival at 6 Months for Patients
NCT00201734 (6) [back to overview]Objective Response Rate (ORR) for the Phase II Portion of the Study. CR+PR Per RECIST v1.0 Criteria Using a Single Arm , Two Stage Minimax Design.
NCT00201734 (6) [back to overview]One Year Survival for Patients
NCT00215930 (3) [back to overview]Overall Survival (OS)
NCT00215930 (3) [back to overview]Best Disease Response After a Maximum of Six Cycles.
NCT00215930 (3) [back to overview]Progression Free Survival (PFS)
NCT00226590 (4) [back to overview]Number of Participants Whose Response Allowed Them to Proceed to Chemoradiation
NCT00226590 (4) [back to overview]Progression Free Survival
NCT00226590 (4) [back to overview]Treatment Completion
NCT00226590 (4) [back to overview]Overall Survival
NCT00231868 (1) [back to overview]"To Evaluate the Toxicity and Tolerability of Pelvic Radiation Sandwiched Between Cycles of Paclitaxel/Carboplatin Chemotherapy in Patients With UPSC"
NCT00232479 (2) [back to overview]Safety and Tolerability
NCT00232479 (2) [back to overview]Number of Patients With Pathologic Complete Response (pCR)
NCT00232505 (3) [back to overview]Overall Disease Response Rate
NCT00232505 (3) [back to overview]Progression-Free Survival
NCT00232505 (3) [back to overview]Overall Survival
NCT00234052 (7) [back to overview]Overall Survival Rate at 6, 12, 18, and 24 Months
NCT00234052 (7) [back to overview]Overall Survival Rate
NCT00234052 (7) [back to overview]Toxicity of Carboplatin, Pemetrexed and Bevacizumab Combination Treatment
NCT00234052 (7) [back to overview]Duration of Response
NCT00234052 (7) [back to overview]Overall Response Rate
NCT00234052 (7) [back to overview]Median Progression Free Survival
NCT00234052 (7) [back to overview]Progression Free Survival at 6, 12, 18, 24 Months
NCT00238615 (2) [back to overview]Change in Standard Uptake Value (SUVmax) on Positron Emission Tomography (PET) Scans Pre and Post Chemotherapy and Radiation in This Trial and Ability to Predict Surgical Resection Rate, Progression-free Survival and 2 Year Overall Survival
NCT00238615 (2) [back to overview]2 Year Overall Survival After a Combination of Chemotherapy, Radiation and Surgery in Stage III NSCLC Patients Following the Protocol Therapy.
NCT00240097 (3) [back to overview]Objective Response Rate (Part I)
NCT00240097 (3) [back to overview]Progression Free Survival (Part I)
NCT00240097 (3) [back to overview]Overall Survival (Part I)
NCT00247416 (4) [back to overview]Progression-free Survival
NCT00247416 (4) [back to overview]Effect of Dexamethasone Pre-treatment on Overall Survival.
NCT00247416 (4) [back to overview]Effect of Dexamethasone Pre-treatment on Response Rate.
NCT00247416 (4) [back to overview]Percentage of Participants With Reduction in Grade 3/4 Neutropenia
NCT00248287 (4) [back to overview]Objective Response Rates (ORR)
NCT00248287 (4) [back to overview]Median Overall Survival (OS)
NCT00248287 (4) [back to overview]Median Time of Progression-free Survival (PFS)
NCT00248287 (4) [back to overview]Duration of Response
NCT00253435 (4) [back to overview]Engraftment DLT
NCT00253435 (4) [back to overview]Dose Limiting Veno-occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome SOS
NCT00253435 (4) [back to overview]Response (Complete Response, Very Good Partial Response, and Partial Response) at 60-days Post Stem Cell Infusion
NCT00253435 (4) [back to overview]Event-free Survival (EFS) at 3 Years
NCT00254592 (1) [back to overview]Overall Clinical Response to the Dose Dense Regimen
NCT00255723 (1) [back to overview]Overall Objective Response
NCT00256243 (2) [back to overview]Microscopic Pathological Response Rate
NCT00256243 (2) [back to overview]Clinical Response Rate
NCT00258362 (2) [back to overview]Percent of Patients Estimated to be Progression-Free and Alive
NCT00258362 (2) [back to overview]Percent of Patients Estimated to be Alive
NCT00262847 (4) [back to overview]Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI)
NCT00262847 (4) [back to overview]Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0
NCT00262847 (4) [back to overview]Overall Survival
NCT00262847 (4) [back to overview]Progression-free Survival
NCT00264498 (1) [back to overview]Progression Free Survival (PFS)
NCT00267696 (2) [back to overview]Determine the Antitumor Activity of Gemcitabine/Carboplatin/Bevacizumab Regimen as Measured by the Probability of Surviving Progression-free for at Least 6 Months or Responding.
NCT00267696 (2) [back to overview]Overall Survival for Patients Treated With the Regimen.
NCT00268437 (2) [back to overview]Overall Survival
NCT00268437 (2) [back to overview]Pathologic Complete Response Rate
NCT00268905 (3) [back to overview]Percent of Subjects With Best Overall Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.
NCT00268905 (3) [back to overview]Safety of Eribulin Mesylate in Combination With Carboplatin as Measured by the Number of Subjects With Treatment Emergent Adverse Events.
NCT00268905 (3) [back to overview]Maximum Tolerated Dose (MTD) of Eribulin Mesylate of E7389 in Combination With Carboplatin in Subjects With Advanced Solid Tumors.
NCT00269152 (5) [back to overview]Overall Survival at 6 Years
NCT00269152 (5) [back to overview]Grade III/IV Adverse Events
NCT00269152 (5) [back to overview]The Feasibility of Post-Surgery Chemotherapy
NCT00269152 (5) [back to overview]3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years
NCT00269152 (5) [back to overview]Overall Survival at 3 Years
NCT00270790 (2) [back to overview]Participants With Mucositis and Hematological Toxicities With the Addition of Radioprotector Amifostine
NCT00270790 (2) [back to overview]Response Rates Based on the Study Regimen
NCT00271505 (3) [back to overview]Time to Progression-Free Survival (PFS)
NCT00271505 (3) [back to overview]Disease Control Rate
NCT00271505 (3) [back to overview]Overall Survival (OS)- 5 Years
NCT00274924 (2) [back to overview]5-year Overall Survival
NCT00274924 (2) [back to overview]2-year Progression-Free Survival (PFS)
NCT00278148 (4) [back to overview]Overall Survival
NCT00278148 (4) [back to overview]Progression Free Survival (PFS)
NCT00278148 (4) [back to overview]Pathological Complete Response Rate
NCT00278148 (4) [back to overview]Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)
NCT00280150 (6) [back to overview]Response Rate to Induction Therapy (Phase I [Closed to Accrual as of 1/3/2008] and II)
NCT00280150 (6) [back to overview]Overall Response Rate and Survival Profile
NCT00280150 (6) [back to overview]Progression-free Survival (PFS)
NCT00280150 (6) [back to overview]Safety and Toxicity Profile of Combining Both Bevacizumab and Erlotinib Hydrochloride With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy
NCT00280150 (6) [back to overview]Maximum Dose of Erlotinib When Given Together With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy (Phase I [Closed to Accrual as of 1/3/2008])
NCT00280150 (6) [back to overview]Feasibility and Tolerability of Administering Consolidation Therapy
NCT00280735 (4) [back to overview]Number of Participants Who Completed Four Cycles of the Carboplatin/Docetaxel Regimen
NCT00280735 (4) [back to overview]Progression Free Survival
NCT00280735 (4) [back to overview]Toxicity in Patients Treated With This Regimen
NCT00280735 (4) [back to overview]Overall Survival
NCT00281827 (6) [back to overview]Number of Patients Alive at 1 Year (Survival)
NCT00281827 (6) [back to overview]Number of Patients Alive at 2 Years (Survival)
NCT00281827 (6) [back to overview]Number of Patients Disease-free at 1 Year
NCT00281827 (6) [back to overview]Number of Patients Disease-free at 2 Years
NCT00281827 (6) [back to overview]Number of Patients Reporting Clinical Response
NCT00281827 (6) [back to overview]Number of Patients Alive at 56 Months (End of Study)
NCT00287989 (2) [back to overview]Overall Response Rate
NCT00287989 (2) [back to overview]Time to Progression
NCT00290537 (1) [back to overview]Number of Participants With Response Following Treatment With 300 mg ZD6474 Daily (Study Part One)
NCT00294762 (6) [back to overview]Overall Survival at 12 Months
NCT00294762 (6) [back to overview]Overall Survival
NCT00294762 (6) [back to overview]Duration of Tumor Response
NCT00294762 (6) [back to overview]6-month Progression-free Survival
NCT00294762 (6) [back to overview]Best Tumor Response
NCT00294762 (6) [back to overview]Progression-free Survival
NCT00295893 (2) [back to overview]Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1.
NCT00295893 (2) [back to overview]Count of Patients With Pathologic Complete Response (pCR)
NCT00300885 (6) [back to overview]Duration of Response
NCT00300885 (6) [back to overview]Progression Free Survival (PFS)
NCT00300885 (6) [back to overview]Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT)
NCT00300885 (6) [back to overview]Overall Survival (OS) in Patients Treated With Carboplatin, Paclitaxel and Sorafenib to OS in Patients Treated With Carboplatin, Paclitaxel and Placebo
NCT00300885 (6) [back to overview]Overall Best Response
NCT00300885 (6) [back to overview]Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT)
NCT00301028 (1) [back to overview]Number of Participants With Complete Response
NCT00303108 (4) [back to overview]Objective Response Rate (ORR)
NCT00303108 (4) [back to overview]Progression-free Survival (PFS)
NCT00303108 (4) [back to overview]Duration of Response
NCT00303108 (4) [back to overview]1-year Overall Survival
NCT00305942 (3) [back to overview]Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
NCT00305942 (3) [back to overview]Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
NCT00305942 (3) [back to overview]Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
NCT00308750 (8) [back to overview]Time to Disease Progression
NCT00308750 (8) [back to overview]Time-to-Treatment Failure (TTF)
NCT00308750 (8) [back to overview]Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale
NCT00308750 (8) [back to overview]Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale
NCT00308750 (8) [back to overview]Duration of CR or PR (Duration of Response)
NCT00308750 (8) [back to overview]Number of Participants With Adverse Events (AEs) or Deaths
NCT00308750 (8) [back to overview]Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response]
NCT00308750 (8) [back to overview]Overall Survival (OS)
NCT00316173 (6) [back to overview]The Number of Participants Classified as Responders in Cancer Antigen 125 (CA-125)
NCT00316173 (6) [back to overview]Duration of Response
NCT00316173 (6) [back to overview]Progression-free Survival
NCT00316173 (6) [back to overview]Number of Participants Who Died From the Start of Treatment to Follow-up
NCT00316173 (6) [back to overview]Time to Response
NCT00316173 (6) [back to overview]Number of Participants With the Indicated Response
NCT00316186 (5) [back to overview]Grade 3 (Severe) Hematological Toxicities
NCT00316186 (5) [back to overview]Grade 1 (Mild) Hematological Toxicities
NCT00316186 (5) [back to overview]Grade 4 (Life-threatening or Disabling) Hematological Toxicities
NCT00316186 (5) [back to overview]Overall Response Rate, as Determined by Radiologic Evaluation (Utilizing the World Health Organization [WHO] Criteria), Calculated as the Number of Participants With the Indicated Response
NCT00316186 (5) [back to overview]Grade 2 (Moderate) Hematological Toxicities
NCT00318136 (4) [back to overview]Adverse Events That Led to Discontinuation of Bevacizumab
NCT00318136 (4) [back to overview]Progression-free Survival
NCT00318136 (4) [back to overview]Selected Adverse Events
NCT00318136 (4) [back to overview]Incidence of Grade ≥3 Pulmonary Hemorrhage Adverse Events
NCT00322452 (16) [back to overview]Nausea
NCT00322452 (16) [back to overview]Neurotoxicity
NCT00322452 (16) [back to overview]Vomiting
NCT00322452 (16) [back to overview]Symptom Improvement as Measured by the Lung Cancer Subscale (LCS) of the FACT-L Questionnaire
NCT00322452 (16) [back to overview]Rashes/Acnes
NCT00322452 (16) [back to overview]Objective Tumour Response Rate According to RECIST
NCT00322452 (16) [back to overview]Quality of Life (QoL) as Measured by the Total Score of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire
NCT00322452 (16) [back to overview]Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Anaemia
NCT00322452 (16) [back to overview]Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Liver Transaminases
NCT00322452 (16) [back to overview]Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Neutropenia
NCT00322452 (16) [back to overview]Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Leukopenia
NCT00322452 (16) [back to overview]Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Thrombocytopenia
NCT00322452 (16) [back to overview]Diarrhoea
NCT00322452 (16) [back to overview]Median Overall Survival (OS) in Months at OS Data Cut Off (14th June 2010)
NCT00322452 (16) [back to overview]Quality of Life (QoL) as Measured by the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire
NCT00322452 (16) [back to overview]Median Progression Free Survival (PFS) in Months
NCT00322881 (1) [back to overview]Therapy Completion Rate
NCT00323869 (9) [back to overview]Stable Disease (SD)
NCT00323869 (9) [back to overview]Response Rate (CR + PR + SD)
NCT00323869 (9) [back to overview]Progression-free Survival (PFS)
NCT00323869 (9) [back to overview]Time-to-First Event
NCT00323869 (9) [back to overview]Partial Response (PR)
NCT00323869 (9) [back to overview]Overall Survival (OS) at 12 Months
NCT00323869 (9) [back to overview]Overall Survival (OS)
NCT00323869 (9) [back to overview]Complete Response (CR)
NCT00323869 (9) [back to overview]Overall Survival (OS) at 24 Months
NCT00325234 (6) [back to overview]Duration of Response (DOR)
NCT00325234 (6) [back to overview]Time to Progressive Disease (PD)
NCT00325234 (6) [back to overview]Time to Response
NCT00325234 (6) [back to overview]Tumor Response Rate
NCT00325234 (6) [back to overview]Number of Participants With Adverse Events (AE)
NCT00325234 (6) [back to overview]Time To Treatment Failure (TTTF)
NCT00326599 (7) [back to overview]Overall Survival at 1 Year After Randomization (Phase II Patients Only)
NCT00326599 (7) [back to overview]Progression-free Survival (Phase II Patients Only)
NCT00326599 (7) [back to overview]Progression-free Survival Rate at 6 Months After Randomization (Phase II Patients Only)
NCT00326599 (7) [back to overview]Time to Treatment Failure (Phase II Patients Only)
NCT00326599 (7) [back to overview]Confirmed Response Rate (Complete Response and Partial Response) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II Patients Only)
NCT00326599 (7) [back to overview]Dose Limiting Toxicity (DLT) (Lead-in Phase Arm I Patients Only)
NCT00326599 (7) [back to overview]Overall Survival (Phase II Patients Only)
NCT00329641 (4) [back to overview]6-month Progression-free Survival
NCT00329641 (4) [back to overview]One-year Overall Survival
NCT00329641 (4) [back to overview]Response Rate (Complete and Partial Response)
NCT00329641 (4) [back to overview]Toxicity
NCT00331422 (3) [back to overview]Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)
NCT00331422 (3) [back to overview]Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy
NCT00331422 (3) [back to overview]Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration
NCT00335556 (6) [back to overview]Long-term Survival of Patients With Stage I-IV Malignant Rhabdoid Tumors
NCT00335556 (6) [back to overview]Number of Patients With INI1 Mutations in Renal and Extrarenal Malignant Rhabdoid Tumor by Fluorescent in Situ Hybridization
NCT00335556 (6) [back to overview]Event-Free Survival of Patients With Diffuse Anaplastic Wilms' Tumor (DAWT)
NCT00335556 (6) [back to overview]Event Free Survival Probability
NCT00335556 (6) [back to overview]Toxicity Rate
NCT00335556 (6) [back to overview]Response Rate
NCT00335738 (9) [back to overview]Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
NCT00335738 (9) [back to overview]Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding
NCT00335738 (9) [back to overview]Pathological Features Present at Diagnosis - Scleral Invasion (SI)
NCT00335738 (9) [back to overview]Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)
NCT00335738 (9) [back to overview]Pathological Features Present At Diagnosis - Iris Infiltration (II)
NCT00335738 (9) [back to overview]Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)
NCT00335738 (9) [back to overview]Overall Survival (OS)
NCT00335738 (9) [back to overview]Event-free Survival (EFS)
NCT00335738 (9) [back to overview]Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)
NCT00336024 (10) [back to overview]Percentage of Participants With Any Acute Adverse Events
NCT00336024 (10) [back to overview]Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI).
NCT00336024 (10) [back to overview]Number of Participants With Secondary Malignancies
NCT00336024 (10) [back to overview]Rates of Nutritional Toxicities
NCT00336024 (10) [back to overview]Number of Participants With Chronic Central Hypothyroidism
NCT00336024 (10) [back to overview]Rates of Gastrointestinal Toxicities
NCT00336024 (10) [back to overview]Number of Participants With Chronic Diabetes Insipidus
NCT00336024 (10) [back to overview]Number of Participants With Chronic Low Somatomedin C
NCT00336024 (10) [back to overview]Number of Participants With Chronic Primary Hypothyroidism/Subclinical Compensatory HypothyroidismHypothyroidism/Subclinical Compensatory Hypothyroidism
NCT00336024 (10) [back to overview]Percentage of Participants With Event Free Survival (EFS)
NCT00343083 (6) [back to overview]Clinical Complete Response Rate of This Regimen in the Population
NCT00343083 (6) [back to overview]Local Regional Control at 2 Years
NCT00343083 (6) [back to overview]Pathological Response to Cetuximab
NCT00343083 (6) [back to overview]The Primary Endpoint is the Local Regional Control Rate Assessed 3 Months Post Completion of Radiation Therapy.
NCT00343083 (6) [back to overview]Overall Survival and Disease-free Survival
NCT00343083 (6) [back to overview]Percentage of Participants With Grade 3 Toxicities of Cetuximab
NCT00343291 (5) [back to overview]Progression Free Survival (PFS)
NCT00343291 (5) [back to overview]Percentage of Participants Achieving an Objective Overall Response (Overall Response Rate)
NCT00343291 (5) [back to overview]Duration of Overall Response
NCT00343291 (5) [back to overview]Overall Survival
NCT00343291 (5) [back to overview]Percentage of Participants With Symptomatic Response (Symptom Response Rate)
NCT00345540 (3) [back to overview]Progression Free Survival (PFS)
NCT00345540 (3) [back to overview]Response Rate
NCT00345540 (3) [back to overview]Safety of NOV-002 and Carboplatin
NCT00350792 (5) [back to overview]Time to Treatment Failure
NCT00350792 (5) [back to overview]Time to Treatment Failure
NCT00350792 (5) [back to overview]Estimated Probability of One Year Progression-free Survival
NCT00350792 (5) [back to overview]Percentage of Participants With a Complete or Partial Tumor Response (Overall Tumor Response)
NCT00350792 (5) [back to overview]Overall Survival
NCT00352690 (7) [back to overview]Overall Survival (OS) Rate
NCT00352690 (7) [back to overview]Incidence and Severity of Radiation-induced Pneumonitis
NCT00352690 (7) [back to overview]Response Rates
NCT00352690 (7) [back to overview]Failure-free Survival (FFS)
NCT00352690 (7) [back to overview]Failure-free Survival (FFS) Rate
NCT00352690 (7) [back to overview]Overall Survival (OS)
NCT00352690 (7) [back to overview]Incidence and Severity of Radiation-induced Esophagitis
NCT00354107 (1) [back to overview]Response
NCT00356525 (2) [back to overview]Objective Tumor Response
NCT00356525 (2) [back to overview]Overall Survival
NCT00360360 (2) [back to overview]Progression-free Survival
NCT00360360 (2) [back to overview]Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
NCT00362817 (5) [back to overview]Determine the Cause of Death of Patients After Treatment
NCT00362817 (5) [back to overview]The Incidence and Severity of Centeral Nervous System (CNS) Toxicities
NCT00362817 (5) [back to overview]Determine the Overall Survival of Patients
NCT00362817 (5) [back to overview]Analyze Patients Time to Progression
NCT00362817 (5) [back to overview]Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide
NCT00363415 (5) [back to overview]Overall Survival
NCT00363415 (5) [back to overview]Progression Free Survival
NCT00363415 (5) [back to overview]Overall Survival (Subgroups)
NCT00363415 (5) [back to overview]Number of Participants in Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes
NCT00363415 (5) [back to overview]Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L)
NCT00365365 (3) [back to overview]Disease-free Survival (DFS) Rate
NCT00365365 (3) [back to overview]Safety - Number of Participants With Adverse Events (AE)
NCT00365365 (3) [back to overview]Cardiac Safety - Number of Participants With Grade 3-4 Clinical Congestive Heart Failure (CHF)
NCT00373217 (2) [back to overview]Cytotoxic T-cell Response to Vaccine Therapy Comprising 5 Synthetic Ovarian Cancer-associated Peptides, as Assessed Using Peripheral Blood During Course 1
NCT00373217 (2) [back to overview]Cytotoxic T-cell Response to Vaccine Therapy Comprising Synthetic Ovarian Cancer-associated Peptides, as Assessed Using Peripheral Blood During Chemotherapy and During Course 2
NCT00383266 (6) [back to overview]Overall Survival Rate
NCT00383266 (6) [back to overview]Overall Survival (OS)
NCT00383266 (6) [back to overview]Overall Response Rate (ORR)
NCT00383266 (6) [back to overview]Time to Disease Progression
NCT00383266 (6) [back to overview]Toxicities
NCT00383266 (6) [back to overview]Overall Survival Rate
NCT00387660 (3) [back to overview]Median Survival of Patients Treated With This Regimen
NCT00387660 (3) [back to overview]Number of Participants With Toxicity
NCT00387660 (3) [back to overview]Overall Response Rate
NCT00390611 (4) [back to overview]Toxicity of Paclitaxel/Carboplatin vs. Paclitaxel/Carboplatin/Sorafenib
NCT00390611 (4) [back to overview]2-year Progression-free Survival
NCT00390611 (4) [back to overview]Overall Response Rate (ORR)
NCT00390611 (4) [back to overview]Overall Survival (OS)
NCT00391118 (12) [back to overview]PK: AUC0-∞ for Paclitaxel With and Without Enzastaurin for Part 1 of Study
NCT00391118 (12) [back to overview]PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study
NCT00391118 (12) [back to overview]Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)
NCT00391118 (12) [back to overview]Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs) and the Number of Participants Who Died (To Compare the Safety of the 2 Treatments)
NCT00391118 (12) [back to overview]PK: Cmax for Paclitaxel With and Without Enzastaurin for Part 1 of Study
NCT00391118 (12) [back to overview]Part 2: Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]
NCT00391118 (12) [back to overview]Part 2: Percentage of Participants With PFS at 2 Years
NCT00391118 (12) [back to overview]Part 2: Progression-Free Survival (PFS)
NCT00391118 (12) [back to overview]Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response)
NCT00391118 (12) [back to overview]Pharmacokinetics (PK): Maximum Concentration (Cmax) for Carboplatin With and Without Enzastaurin for Part 1 of Study
NCT00391118 (12) [back to overview]PK: AUC From Time 0 to Infinity (AUC0-∞) for Carboplatin With and Without Enzastaurin for Part 1 of Study
NCT00391118 (12) [back to overview]PK: AUC During the Dosing Interval at Steady State (AUCτ,ss) for Part 2 of Study
NCT00392327 (14) [back to overview]Tumor Response to Radiation Therapy for Patients With Medulloblastoma
NCT00392327 (14) [back to overview]The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients
NCT00392327 (14) [back to overview]The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
NCT00392327 (14) [back to overview]The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients
NCT00392327 (14) [back to overview]Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma
NCT00392327 (14) [back to overview]Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
NCT00392327 (14) [back to overview]Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma
NCT00392327 (14) [back to overview]Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
NCT00392327 (14) [back to overview]Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)
NCT00392327 (14) [back to overview]Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients
NCT00392327 (14) [back to overview]Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients
NCT00392327 (14) [back to overview]Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients
NCT00392327 (14) [back to overview]Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients
NCT00392327 (14) [back to overview]The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients
NCT00393068 (3) [back to overview]Progression-Free Survival
NCT00393068 (3) [back to overview]Pathologic Complete Response (pCR) Rate
NCT00393068 (3) [back to overview]Overall Survival
NCT00400803 (5) [back to overview]Time to Best Response
NCT00400803 (5) [back to overview]Overall Survival Time
NCT00400803 (5) [back to overview]Time to Progression
NCT00400803 (5) [back to overview]Best Overall Response by Cycle
NCT00400803 (5) [back to overview]Duration of Response
NCT00402051 (5) [back to overview]Time to Treatment Failure (TTF)
NCT00402051 (5) [back to overview]Pharmacology Toxicities
NCT00402051 (5) [back to overview]Number of Participants With Tumor Response (as Basis for Response Rate)
NCT00402051 (5) [back to overview]Percentage of Participants Surviving Progression-Free at 6 Months (Progression Free Survival [PFS] Rate)
NCT00402051 (5) [back to overview]Overall Survival
NCT00404235 (5) [back to overview]Number of Treatment Cycles Administered
NCT00404235 (5) [back to overview]Time to Disease Progression
NCT00404235 (5) [back to overview]Tumor Response Rate, as Measured by RECIST Criteria
NCT00404235 (5) [back to overview]Duration of Response
NCT00404235 (5) [back to overview]Survival Time
NCT00408070 (1) [back to overview]Progression Free Survival Rate at 9 Months
NCT00413283 (6) [back to overview]Platelet Count on Day 22
NCT00413283 (6) [back to overview]Duration of Grade 3 or 4 Thrombocytopenia
NCT00413283 (6) [back to overview]Gemcitabine Dose Reduction on Day 8 of the First Chemotherapy Cycle
NCT00413283 (6) [back to overview]Number of Participants With Adverse Events
NCT00413283 (6) [back to overview]Number of Participants With Platelet Transfusions
NCT00413283 (6) [back to overview]Number of Participants Experiencing Grade 3 or 4 Thrombocytopenia During the First Treatment Cycle.
NCT00416793 (2) [back to overview]Overall Survival Rate at 6 Months
NCT00416793 (2) [back to overview]Overall Response Rate
NCT00421889 (9) [back to overview]Time to Progression
NCT00421889 (9) [back to overview]Maximum Tolerable Dose (MTD) Belinostat, Part A,
NCT00421889 (9) [back to overview]Duration of Response
NCT00421889 (9) [back to overview]Dose Limiting Toxicities (DLT), Part A
NCT00421889 (9) [back to overview]Best Overall Response (CR or PR)
NCT00421889 (9) [back to overview]Belinostat Mean t½
NCT00421889 (9) [back to overview]Belinostat Cmax
NCT00421889 (9) [back to overview]Belinostat AUC (0-infinity)
NCT00421889 (9) [back to overview]Time to Response
NCT00423852 (2) [back to overview]Response
NCT00423852 (2) [back to overview]Maximum Tolerated Dose of Ifosfamide
NCT00424840 (1) [back to overview]Number of Subjects Who Require Dose Delay/Reduction in Dose of Bortezomibin the First Cycle
NCT00429182 (2) [back to overview]Median Progression Free Survival (PFS)
NCT00429182 (2) [back to overview]Number of Participants With Reduction in CTCs Following High-dose Chemotherapy With Purged Autologous Stem Cell Products
NCT00432094 (5) [back to overview]Engraftment of Neutrophils
NCT00432094 (5) [back to overview]Disease-free Survival (DFS)
NCT00432094 (5) [back to overview]Overall Survival (OS)
NCT00432094 (5) [back to overview]Numbers of Patients Unable to Mobilize Peripheral Blood Stem Cells
NCT00432094 (5) [back to overview]Engraftment of Platelets
NCT00432172 (1) [back to overview]Clinical Response Rate
NCT00434226 (5) [back to overview]Incidence of Grade ≥ 3 Adverse Events
NCT00434226 (5) [back to overview]Best Response
NCT00434226 (5) [back to overview]Incidence of Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction
NCT00434226 (5) [back to overview]Incidence of Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption
NCT00434226 (5) [back to overview]Serious Adverse Events
NCT00434252 (8) [back to overview]Percentage of Participants With an Objective Response
NCT00434252 (8) [back to overview]Duration of Objective Response
NCT00434252 (8) [back to overview]Number of Participants With Objective Response
NCT00434252 (8) [back to overview]Number of Participants With Select Adverse Events
NCT00434252 (8) [back to overview]Twenty-Four Week Landmark Stable Disease
NCT00434252 (8) [back to overview]Overall Survival (OS)
NCT00434252 (8) [back to overview]Progression-free Survival
NCT00434252 (8) [back to overview]Six-month Landmark Survival Rate
NCT00434642 (6) [back to overview]Overall Survival
NCT00434642 (6) [back to overview]Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)
NCT00434642 (6) [back to overview]Duration of Objective Response (OR) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)
NCT00434642 (6) [back to overview]Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)
NCT00434642 (6) [back to overview]Percentage of Patients Who Had a Gastrointestinal Perforation (GIP)
NCT00434642 (6) [back to overview]Percentage of Patients Who Had at Least 1 Adverse Event
NCT00439608 (2) [back to overview]Reponse Rate at Time of Surgery by Tissue
NCT00439608 (2) [back to overview]Number of Participants With Grade 2 and/or 3 Rash in Patients With Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus, Gastroesophageal Junction, or Stomach.
NCT00446030 (1) [back to overview]Percent of Participants With Grade 3/4 Clinical Congestive Heart Failure (CHF)
NCT00453154 (4) [back to overview]Number of Participants With Overall Tumor Response
NCT00453154 (4) [back to overview]Progression-free Survival (Phase II)
NCT00453154 (4) [back to overview]Maximum Tolerated of Sunitinib Combined With Cisplatin and Etoposide (Phase I)
NCT00453154 (4) [back to overview]Overall Survival
NCT00454324 (4) [back to overview]Number of Individuals With Adverse Events
NCT00454324 (4) [back to overview]Progression Free Survival (PFS)
NCT00454324 (4) [back to overview]Overall Response Rate
NCT00454324 (4) [back to overview]1-year Overall Survival (OS)
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Pemetrexed
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Gemcitabine
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Docetaxel
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Carboplatin
NCT00454649 (34) [back to overview]Apparent Oral Clearance (CL/F) for Capecitabine
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Pemetrexed
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Paclitaxel
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Gemcitabine
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Docetaxel
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Cisplatin
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Carboplatin
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Cisplatin
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Docetaxel
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Axitinib (AG-013736)
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Carboplatin
NCT00454649 (34) [back to overview]Plasma Decay Half Life (t1/2) for Capecitabine
NCT00454649 (34) [back to overview]Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Gemcitabine
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Paclitaxel
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Pemetrexed
NCT00454649 (34) [back to overview]Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy
NCT00454649 (34) [back to overview]Percentage of Participants With Objective Response
NCT00454649 (34) [back to overview]Plasma Clearance (CL) for Carboplatin
NCT00454649 (34) [back to overview]Plasma Clearance (CL) for Cisplatin
NCT00454649 (34) [back to overview]Plasma Clearance (CL) for Docetaxel
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Capecitabine
NCT00454649 (34) [back to overview]Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine
NCT00454649 (34) [back to overview]Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)
NCT00454649 (34) [back to overview]Plasma Clearance (CL) for Gemcitabine
NCT00454649 (34) [back to overview]Plasma Clearance (CL) for Paclitaxel
NCT00454649 (34) [back to overview]Plasma Clearance (CL) for Pemetrexed
NCT00456261 (3) [back to overview]Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease
NCT00456261 (3) [back to overview]Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
NCT00456261 (3) [back to overview]Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
NCT00461851 (2) [back to overview]Progression Free Survival (PFS)
NCT00461851 (2) [back to overview]Dose Ruction (Toxicity)
NCT00467051 (2) [back to overview]The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.
NCT00467051 (2) [back to overview]Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
NCT00469898 (4) [back to overview]Overall Survival
NCT00469898 (4) [back to overview]Time to Progression
NCT00469898 (4) [back to overview]Number of Patients With Adverse Events
NCT00469898 (4) [back to overview]Patient Response
NCT00473889 (3) [back to overview]Number of Participants Who Had a Disease Response to Treatment
NCT00473889 (3) [back to overview]Progression Free Survival
NCT00473889 (3) [back to overview]Overall Survival
NCT00479674 (2) [back to overview]"Best Clinical Response Expressed as Percentage of Participants Treated With Combination Regimen of Weekly Abraxane® and Carboplatin Plus Biweekly Bevacizumab to Treat Women With Stage IV or Inoperable Stage III Triple Negative Metastatic Breast Cancer."
NCT00479674 (2) [back to overview]Median Proportion Progression-free as Estimated by Kaplan-Meier Methods
NCT00481078 (3) [back to overview]Progression-free Survival
NCT00481078 (3) [back to overview]Overall Survival
NCT00481078 (3) [back to overview]Response Rate
NCT00482014 (9) [back to overview]Phase 2 - Time to Progression
NCT00482014 (9) [back to overview]Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate)
NCT00482014 (9) [back to overview]Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs)
NCT00482014 (9) [back to overview]Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate)
NCT00482014 (9) [back to overview]Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events
NCT00482014 (9) [back to overview]Phase 2 - Survival Probability at 2 Years
NCT00482014 (9) [back to overview]Phase 2 - Median Survival
NCT00482014 (9) [back to overview]Phase 1 - Maximum Tolerated Dose (MTD) of Cisplatin
NCT00482014 (9) [back to overview]Phase 1 - Maximum Tolerated Dose (MTD) of Carboplatin
NCT00483223 (4) [back to overview]Objective Response Rate Categorized by Subgroup
NCT00483223 (4) [back to overview]Objective Response Rate
NCT00483223 (4) [back to overview]Progression Free Survival and Overall Survival
NCT00483223 (4) [back to overview]Response Rate Categorized by p63/p73 Ratio
NCT00489359 (12) [back to overview]Phase 2 - Time to Treatment Failure
NCT00489359 (12) [back to overview]Phase 2 - Time to Response (TTR)
NCT00489359 (12) [back to overview]Phase 2 - Time to Disease Progression
NCT00489359 (12) [back to overview]Phase 2 - Progression-Free Survival
NCT00489359 (12) [back to overview]Phase 2 - Number of Participants With Adverse Events (Toxicity)
NCT00489359 (12) [back to overview]Phase 1 - Number of Participants With Tumor Response
NCT00489359 (12) [back to overview]Phase 2 - Percentage of Participants With Overall Tumor Response (Response Rate)
NCT00489359 (12) [back to overview]Phase 1 - Number of Dose-Limiting Toxicities (DLTs)
NCT00489359 (12) [back to overview]Phase 1 - Recommended Dose of Pemetrexed for Phase 2
NCT00489359 (12) [back to overview]Phase 1 - Recommended Area Under the Curve (AUC) Dose of Carboplatin for Phase 2
NCT00489359 (12) [back to overview]Phase 2 - Duration of Response (DOR)
NCT00489359 (12) [back to overview]Phase 1 - Number of Participants With Adverse Events (Toxicity)
NCT00494026 (1) [back to overview]Pharmacology Toxicity
NCT00495170 (1) [back to overview]Overall Survival and Progression Free Survival
NCT00499109 (3) [back to overview]Response Rate (RR)
NCT00499109 (3) [back to overview]Progression Free Survival (PFS)
NCT00499109 (3) [back to overview]Overall Survival (OS)
NCT00499616 (14) [back to overview]Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment
NCT00499616 (14) [back to overview]Comparison Between Reduce Intensity of Therapy for Patients With Stage 4 Neuroblastoma and Favorable Biological Features and Patients < 1 Year of Age With Stage 4 Neuroblastoma Treated on COG-A3961
NCT00499616 (14) [back to overview]Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961
NCT00499616 (14) [back to overview]Image Defined Risk Factor (IDRF)
NCT00499616 (14) [back to overview]Neurologic Symptoms
NCT00499616 (14) [back to overview]Overall Survival (OS) Rates
NCT00499616 (14) [back to overview]Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma
NCT00499616 (14) [back to overview]Second-event-free Survival (E2FS)
NCT00499616 (14) [back to overview]Second-Overall Survival
NCT00499616 (14) [back to overview]Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS)
NCT00499616 (14) [back to overview]Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates
NCT00499616 (14) [back to overview]Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate
NCT00499616 (14) [back to overview]Definitive Determination of the Prognostic Ability of 1p and 11q
NCT00499616 (14) [back to overview]Definitive Determination of the Prognostic Ability of 1p and 11q
NCT00501644 (1) [back to overview]Number of Patients With Response
NCT00502203 (1) [back to overview]Number of Participants With Overall Response
NCT00507429 (2) [back to overview]Overall Survival
NCT00507429 (2) [back to overview]To Determine Percentage of 1 Year Survival
NCT00514540 (2) [back to overview]Median Time to Progression (TTP)
NCT00514540 (2) [back to overview]Response Rate of Salvage Chemotherapy With Etoposide Plus Cisplatin Following Treatment With Docetaxel Plus Carboplatin.
NCT00520013 (3) [back to overview]Consolidation Treatment-related Toxicity Rate
NCT00520013 (3) [back to overview]Consolidation Objective Response Rate
NCT00520013 (3) [back to overview]Consolidation Progression-Free Survival
NCT00520676 (8) [back to overview]Duration of Response
NCT00520676 (8) [back to overview]Percentage of Participants With Tumor Response (Response Rate)
NCT00520676 (8) [back to overview]Number of Participants With Adverse Events (AEs)
NCT00520676 (8) [back to overview]Survival Without Grade 4 Toxicity
NCT00520676 (8) [back to overview]Survival Without Grade 3 or 4 Toxicity
NCT00520676 (8) [back to overview]Survival Without Clinically Important Grade 3 or 4 Toxicity
NCT00520676 (8) [back to overview]Overall Survival (OS)
NCT00520676 (8) [back to overview]Progression-free Survival (PFS)
NCT00520975 (10) [back to overview]Number of Patients Experiencing Congestive Heart Failure
NCT00520975 (10) [back to overview]Change in Level of Experiencing Side Effects Between Baseline and Cycle 6 Induction
NCT00520975 (10) [back to overview]Change in Neurotoxicity Level Between Baseline and Cycle 6 Induction
NCT00520975 (10) [back to overview]Change in Fatigue Level Between Baseline and Cycle 6 Induction
NCT00520975 (10) [back to overview]Change in FACT/NCCN Breast Symptom Index (FBSI) Between Baseline and Cycle 6 Induction
NCT00520975 (10) [back to overview]Progression-free Survival
NCT00520975 (10) [back to overview]Number of Circulating Tumor Cells at Baseline
NCT00520975 (10) [back to overview]Overall Response Rate
NCT00520975 (10) [back to overview]Overall Survival
NCT00520975 (10) [back to overview]Proportion of Progression-free at 6 Months
NCT00526890 (7) [back to overview]Selenium Level by Incidence of SAE
NCT00526890 (7) [back to overview]Response Rate
NCT00526890 (7) [back to overview]Overall Survival
NCT00526890 (7) [back to overview]Incidence of Grade 3-4 Pneumonitis
NCT00526890 (7) [back to overview]Failure-free Survival
NCT00526890 (7) [back to overview]Incidence of Grade 3-4 Myelosuppression
NCT00526890 (7) [back to overview]Incidence of Grade 3-4 Esophagitis
NCT00527735 (22) [back to overview]Overall Survival in Participants With NSCLC
NCT00527735 (22) [back to overview]Overall Survival in Participants With SCLC
NCT00527735 (22) [back to overview]Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria
NCT00527735 (22) [back to overview]Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC
NCT00527735 (22) [back to overview]Immune-related Best Overall Response Rate (irBORR) Per irRC in Participants With NSCLC and Small-cell Lung Cancer (SCLC)
NCT00527735 (22) [back to overview]Immune-related Disease Control Rate (irDCR) Per irRC and Disease Control Rate (DCR) Per mWHO Criteria in Participants With NSCLC and SCLC
NCT00527735 (22) [back to overview]Immune-related Duration of Response (irDoR) Per irRC and DoR Per mWHO Criteria in Participants With NSCLC and SCLC
NCT00527735 (22) [back to overview]Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
NCT00527735 (22) [back to overview]Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade
NCT00527735 (22) [back to overview]Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria
NCT00527735 (22) [back to overview]Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
NCT00527735 (22) [back to overview]Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline
NCT00527735 (22) [back to overview]Number of Participants With SCLC With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs by Worst CTC Grade
NCT00527735 (22) [back to overview]Number of Participants With NSCLC Who Have Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Adverse Events (AEs), AEs Leading to Discontinuation, and Drug-related AEs by Worst Common Terminology Criteria (CTC) Grade
NCT00527735 (22) [back to overview]Immune-related Progression-free Survival (irPFS) in Participants With Nonsmall-cell Lung Cancer (NSCLC) Per Immune-related Response Criteria (irRC)
NCT00527735 (22) [back to overview]Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade
NCT00527735 (22) [back to overview]Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade
NCT00527735 (22) [back to overview]Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade
NCT00527735 (22) [back to overview]irPFS in Participants With SCLC Per irRC
NCT00527735 (22) [back to overview]Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline
NCT00527735 (22) [back to overview]Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings
NCT00527735 (22) [back to overview]Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade
NCT00533429 (6) [back to overview]Time to Progressive Disease (TTPD)
NCT00533429 (6) [back to overview]Progression-Free Survival (PFS)
NCT00533429 (6) [back to overview]Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate)
NCT00533429 (6) [back to overview]Overall Survival (OS)
NCT00533429 (6) [back to overview]Duration of Response (DoR)
NCT00533429 (6) [back to overview]Pharmacology Toxicity and Adverse Events (AEs)
NCT00533949 (13) [back to overview]Percentage of Patients With Decline From Baseline to 3 Months in the Lung Cancer Subscale (LCS) of the Functional Assessment of the Cancer Therapy Trial Outcome Index (FACT-TOI).
NCT00533949 (13) [back to overview]Local-regional Failure (Reported as Two-year Estimates)
NCT00533949 (13) [back to overview]Prognostic Value of Pre-treatment Standardized Uptake Value (SUV) of Positron Emission Tomography (PET) Scan in Predicting Survival, Distant Metastasis, and Local-regional Failure
NCT00533949 (13) [back to overview]Percentage of Participants With Grade 3-5 Esophagitis and Pneumonitis Adverse Events as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0
NCT00533949 (13) [back to overview]Overall Survival and Local-regional Failure by Epithelial Growth Factor Receptor (EGFR) Group
NCT00533949 (13) [back to overview]Progression-free Survival
NCT00533949 (13) [back to overview]Prognostic and Predictive Effects of Gross Tumor Volume (GTV) on Overall Survival
NCT00533949 (13) [back to overview]Percentage of Patients With Grade 3+ Adverse Events by Epithelial Growth Factor Receptor (EGFR) Group
NCT00533949 (13) [back to overview]Percentage of Participants With Other Grade 3-5 Adverse Events as Assessed by NCI CTCAE v3.0
NCT00533949 (13) [back to overview]Patient-reported Swallowing Score (Area Under the Curve)
NCT00533949 (13) [back to overview]Overall Survival
NCT00533949 (13) [back to overview]EuroQoL (EQ5D) Visual Analog Scale (VAS) Through One Year (Area Under the Curve)
NCT00533949 (13) [back to overview]Death During or Within 30 Days of Discontinuation of Protocol Treatment
NCT00536601 (8) [back to overview]Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)
NCT00536601 (8) [back to overview]Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)
NCT00536601 (8) [back to overview]Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)
NCT00536601 (8) [back to overview]Response Rate (Complete Remission)
NCT00536601 (8) [back to overview]Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)
NCT00536601 (8) [back to overview]Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)
NCT00536601 (8) [back to overview]Regimen-related Toxicity Grade 2-4 in Any Organ (Measured by Bearman Score, Values Range From 0 (None) to 4 (Fatal))
NCT00536601 (8) [back to overview]Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors)
NCT00539500 (3) [back to overview]Engraftment Failure Rate
NCT00539500 (3) [back to overview]Number of Treated Participants With Engraftment Failure at Day 42
NCT00539500 (3) [back to overview]Number of Participants With Device-related Toxicity Associated With Transplantation of CD133+ Cells
NCT00540514 (12) [back to overview]Progression-free Survival by Blinded Radiology Assessment
NCT00540514 (12) [back to overview]Percentage of Participants With Controlled Disease
NCT00540514 (12) [back to overview]Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment
NCT00540514 (12) [back to overview]Duration of Response in Responding Patients
NCT00540514 (12) [back to overview]Maximal Degree of Anemia Based on Clinical Laboratory Values for Hemoglobin
NCT00540514 (12) [back to overview]Overall Participant Survival
NCT00540514 (12) [back to overview]Maximal Degree of Neutropenia Based on Clinical Laboratory Values of Absolute Neutrophil Count
NCT00540514 (12) [back to overview]Maximal Degree of Thrombocytopenia Based on Clinical Laboratory Values of Platelet Count
NCT00540514 (12) [back to overview]Time to Improvement of ≥ Grade 3 Treatment Related Peripheral Neuropathy
NCT00540514 (12) [back to overview]SPARC Status and Correlation With Overall Survival
NCT00540514 (12) [back to overview]Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment, by Histology
NCT00540514 (12) [back to overview]Number of Participants With Adverse Events (AEs)
NCT00542191 (1) [back to overview]1) Pathologic Response
NCT00544648 (8) [back to overview]Response (Phase II)
NCT00544648 (8) [back to overview]Response (Phase I)
NCT00544648 (8) [back to overview]Number of Patients With Each Worst Grade Toxicity (Phase II)
NCT00544648 (8) [back to overview]Progression-free Survival (Phase II)
NCT00544648 (8) [back to overview]Progression-free Survival (Phase I)
NCT00544648 (8) [back to overview]Overall Survival (Phase I)
NCT00544648 (8) [back to overview]Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I)
NCT00544648 (8) [back to overview]Number of Patients With Each Worst Grade Toxicity (Phase I)
NCT00550537 (4) [back to overview]Number of Patients With Worst-grade Toxicities Per Grade
NCT00550537 (4) [back to overview]Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
NCT00550537 (4) [back to overview]Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
NCT00550537 (4) [back to overview]Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC
NCT00553462 (3) [back to overview]Response Rate
NCT00553462 (3) [back to overview]Progression-free Survival
NCT00553462 (3) [back to overview]Overall Survival at 12 Months
NCT00554788 (3) [back to overview]Response Rate to the Induction Phase of the Regimen
NCT00554788 (3) [back to overview]Event-free Survival (EFS)
NCT00554788 (3) [back to overview]Percentage of Participants With Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
NCT00558636 (7) [back to overview]Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST)
NCT00558636 (7) [back to overview]Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 7
NCT00558636 (7) [back to overview]Overall Survival (OS)
NCT00558636 (7) [back to overview]Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2
NCT00558636 (7) [back to overview]Progression Free Survival
NCT00558636 (7) [back to overview]Duration of Response
NCT00558636 (7) [back to overview]Change From Baseline of Health-Related Quality of Life (HRQoL) Score Assessed at Treatment Cycle 3 and Cycle 5
NCT00563784 (2) [back to overview]Time To First Disease Progression
NCT00563784 (2) [back to overview]Overall Survival and Disease Local Control Rate
NCT00564733 (1) [back to overview]Overall Response Rate (Patients That Achieve a CR or PR)
NCT00565851 (9) [back to overview]Patient Reported Physical Function (Chemotherapy Analysis)
NCT00565851 (9) [back to overview]To Determine if the Addition of Bevacizumab Increases the Duration of Overall Survival Relative to Second-line Paclitaxel and Carboplatin Alone in Patients With Recurrent Platinum Sensitive Epithelial Ovarian, Peritoneal Primary or Fallopian Tube Cancer
NCT00565851 (9) [back to overview]To Determine if Surgical Secondary Cytoreduction in Addition to Adjuvant Chemotherapy Increases the Duration of Overall Survival in Patients With Recurrent Platinum Sensitive Epithelial Ovarian Cancer, Peritoneal Primary or Fallopian Tube Cancer
NCT00565851 (9) [back to overview]Patient Reported Quality of Life (Surgery Analysis)
NCT00565851 (9) [back to overview]Patient Reported Quality of Life (Chemotherapy Analysis)
NCT00565851 (9) [back to overview]Patient Reported Physical Functioning (Surgery Analysis)
NCT00565851 (9) [back to overview]Summary of Adverse Events (CTCAE Version 4.0)
NCT00565851 (9) [back to overview]Progression-free Survival (Chemotherapy Analysis)
NCT00565851 (9) [back to overview]Progression Free Survival (Surgery Analysis)
NCT00567567 (14) [back to overview]OS in Patients 12-18 Months, Stage 4, MYCN Nonamplified Tumor/Unfavorable Histopathology/Diploid DNA Content/Indeterminant Histology/Ploidy and Patients > 547 Days, Stage 3, MYCN Nonamplified Tumor AND Unfavorable Histopathology/Indeterminant Histology
NCT00567567 (14) [back to overview]Proportion of Patients With a Polymorphism
NCT00567567 (14) [back to overview]Peak Serum Concentration of Isotretinoin in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies
NCT00567567 (14) [back to overview]Intraspinal Extension
NCT00567567 (14) [back to overview]Response After Induction Therapy
NCT00567567 (14) [back to overview]Topotecan Systemic Clearance
NCT00567567 (14) [back to overview]Event-free Survival Rate
NCT00567567 (14) [back to overview]Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells
NCT00567567 (14) [back to overview]Duration of Greater Than or Equal to Grade 3 Neutropenia
NCT00567567 (14) [back to overview]Duration of Greater Than or Equal to Grade 3 Thrombocytopenia
NCT00567567 (14) [back to overview]Type of Surgical or Radiotherapy Complication
NCT00567567 (14) [back to overview]EFS Pts Non-randomly Assigned to Single CEM (12-18 Mths, Stg. 4, MYCN Nonamplified Tumor/Unfavorable or Indeterminant Histopathology/Diploid DNA Content & Pts>547 Days, Stg.3, MYCN Nonamplified Tumor AND Unfavorable or Indeterminant Histopathology).
NCT00567567 (14) [back to overview]Incidence Rate of Local Recurrence
NCT00567567 (14) [back to overview]Surgical Response
NCT00568451 (3) [back to overview]Survival Time
NCT00568451 (3) [back to overview]Time to Disease Progression
NCT00568451 (3) [back to overview]Number of Participants With an Objective Tumor Status of Either a Complete Response(CR) or Partial Response (PR), According to RECIST (Response Evaluation Criteria in Solid Tumors) Criteria
NCT00570674 (9) [back to overview]Change in FACT-H&N Score From Baseline to 24 Months
NCT00570674 (9) [back to overview]Change in FACT-H&N Score From Baseline to 12 Months
NCT00570674 (9) [back to overview]Overall Response Rate [Phase I]
NCT00570674 (9) [back to overview]Abraxane Maximum Tolerated Dose (MTD) [Phase I]
NCT00570674 (9) [back to overview]2-Year Overall Survival [Phase I]
NCT00570674 (9) [back to overview]Change in FACT-H&N Score From Baseline to 4 Months
NCT00570674 (9) [back to overview]Duration PEG Therapy
NCT00570674 (9) [back to overview]Change in FACT-H&N Score From Baseline to 6 Months
NCT00570674 (9) [back to overview]Dose Limiting Toxicity (DLT) [Phase I]
NCT00580983 (2) [back to overview]Percentage of Participants With Grade 0-1 Observer-rated Dysphagia
NCT00580983 (2) [back to overview]The Mean Esophageal Radiotherapy Dose in Patients With Strictures and Without Strictures
NCT00581971 (2) [back to overview]Response as Evaluated by Recurrence of Diseases
NCT00581971 (2) [back to overview]Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck.
NCT00583622 (1) [back to overview]Participant Response
NCT00584857 (2) [back to overview]3-year Overall Survival
NCT00584857 (2) [back to overview]Toxicity
NCT00584909 (2) [back to overview]Toxicity
NCT00584909 (2) [back to overview]Disease-free Survival
NCT00585689 (1) [back to overview]Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment
NCT00588094 (1) [back to overview]Improve the Overall Response Rate
NCT00588666 (2) [back to overview]Evaluate the Time to Disease Progression
NCT00588666 (2) [back to overview]The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC.
NCT00588770 (3) [back to overview]Progression-free Survival (PFS)
NCT00588770 (3) [back to overview]Overall Survival (OS)
NCT00588770 (3) [back to overview]Overall Response Rate
NCT00596830 (4) [back to overview]Percentage of Participants With Objective Response (OR)
NCT00596830 (4) [back to overview]Progression-Free Survival (PFS)
NCT00596830 (4) [back to overview]Number of Participants With Total Anti-drug Antibodies (ADA)
NCT00596830 (4) [back to overview]Overall Survival (OS)
NCT00599755 (6) [back to overview]Change in FDG-PET Uptake From Baseline to Week 3
NCT00599755 (6) [back to overview]Change in FDG-PET Uptake From Week 3 to Week 6
NCT00599755 (6) [back to overview]Repeatability of FDG SUVmean at Baseline
NCT00599755 (6) [back to overview]Change in FGD-PET Uptake From Baseline to Week 6
NCT00599755 (6) [back to overview]Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy at a Threshold of a 20% Decrease in SUVmean
NCT00599755 (6) [back to overview]Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy At a Threshold of a 30% Decrease in SUVmean
NCT00600821 (9) [back to overview]Progression Free Survival (PFS)
NCT00600821 (9) [back to overview]Circulating Endothelial Cells (CEC) in Blood
NCT00600821 (9) [back to overview]Duration of Response (DR)
NCT00600821 (9) [back to overview]Overall Survival (OS)
NCT00600821 (9) [back to overview]Percentage of Participants With Objective Response (OR)
NCT00600821 (9) [back to overview]Plasma Concentration of Soluble Proteins
NCT00600821 (9) [back to overview]European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score
NCT00600821 (9) [back to overview]Circulating Endothelial Cells (CEC) in Blood: Total CEC
NCT00600821 (9) [back to overview]European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score
NCT00601718 (4) [back to overview]Safety and Toxicity According to CTCAE v3.0
NCT00601718 (4) [back to overview]Ability to Proceed to Peripheral Blood Stem Cell Collection Following Treatment
NCT00601718 (4) [back to overview]Efficacy (Response Rate) of Vorinostat Combined With RICE Chemotherapy
NCT00601718 (4) [back to overview]Maximum Tolerated Dose of Vorinostat
NCT00602667 (62) [back to overview]Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received
NCT00602667 (62) [back to overview]Feasibility and Toxicity of Administering Consolidation Therapy Including Cyclophosphamide and Pharmacokinetically Targeted Topotecan to Patients With Metastatic Disease Based on the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
NCT00602667 (62) [back to overview]Event-free Survival (EFS) Compared to Historical Controls
NCT00602667 (62) [back to overview]Erlotinib AUC0-24h
NCT00602667 (62) [back to overview]Erlotinib Apparent Volume of Central Compartment
NCT00602667 (62) [back to overview]Erlotinib Apparent Oral Clearance
NCT00602667 (62) [back to overview]Cyclophosphamide Clearance in Induction Chemotherapy
NCT00602667 (62) [back to overview]Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2
NCT00602667 (62) [back to overview]Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1
NCT00602667 (62) [back to overview]Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
NCT00602667 (62) [back to overview]Cyclophosphamide AUC0-24h in Induction Chemotherapy
NCT00602667 (62) [back to overview]Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
NCT00602667 (62) [back to overview]Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
NCT00602667 (62) [back to overview]Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1
NCT00602667 (62) [back to overview]CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1
NCT00602667 (62) [back to overview]CEPM AUC0-24h in Induction Chemotherapy
NCT00602667 (62) [back to overview]CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2
NCT00602667 (62) [back to overview]CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1
NCT00602667 (62) [back to overview]4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1
NCT00602667 (62) [back to overview]4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy
NCT00602667 (62) [back to overview]4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2
NCT00602667 (62) [back to overview]4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1
NCT00602667 (62) [back to overview]Pharmacogenetic Variation on Central Nervous System Transmitters
NCT00602667 (62) [back to overview]Numbers of Patients With Molecular Abnormalities by Tumor Type
NCT00602667 (62) [back to overview]Numbers of Patients With Gene Alterations
NCT00602667 (62) [back to overview]Number of Successful Collections for Frozen and Fixed Tumor Samples
NCT00602667 (62) [back to overview]Number of Participants With Chromosomal Abnormalities
NCT00602667 (62) [back to overview]Number and Type of Genetic Polymorphisms
NCT00602667 (62) [back to overview]Concentration of Cerebrospinal Fluid Neurotransmitters
NCT00602667 (62) [back to overview]Topotecan Clearance in Consolidation Chemotherapy
NCT00602667 (62) [back to overview]Topotecan AUC0-24h in Maintenance Chemotherapy
NCT00602667 (62) [back to overview]Topotecan AUC0-24h in Consolidation Chemotherapy
NCT00602667 (62) [back to overview]Topotecan Apparent Oral Clearance in Maintenance Chemotherapy
NCT00602667 (62) [back to overview]Rate of Local Disease Progression
NCT00602667 (62) [back to overview]Rate of Distant Disease Progression
NCT00602667 (62) [back to overview]Percentage of Patients With Objective Responses Rate to Induction Chemotherapy
NCT00602667 (62) [back to overview]Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup
NCT00602667 (62) [back to overview]Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients
NCT00602667 (62) [back to overview]Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients
NCT00602667 (62) [back to overview]Percent of PET Scans With Loss of Signal Intensity
NCT00602667 (62) [back to overview]Percent of Patients With Sustained Objective Responses Rate After Consolidation
NCT00602667 (62) [back to overview]Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan
NCT00602667 (62) [back to overview]Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan
NCT00602667 (62) [back to overview]Overall Survival (OS) Compared to Historical Controls
NCT00602667 (62) [back to overview]OSI-420 AUC0-24h
NCT00602667 (62) [back to overview]Methotrexate Volume of Central Compartment in Induction Cycle 4
NCT00602667 (62) [back to overview]Methotrexate Volume of Central Compartment in Induction Cycle 3
NCT00602667 (62) [back to overview]Methotrexate Volume of Central Compartment in Induction Cycle 2
NCT00602667 (62) [back to overview]Methotrexate Volume of Central Compartment in Induction Cycle 1
NCT00602667 (62) [back to overview]Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4
NCT00602667 (62) [back to overview]Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3
NCT00602667 (62) [back to overview]Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2
NCT00602667 (62) [back to overview]Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1
NCT00602667 (62) [back to overview]Methotrexate Clearance in Induction Cycle 4
NCT00602667 (62) [back to overview]Methotrexate Clearance in Induction Cycle 3
NCT00602667 (62) [back to overview]Methotrexate Clearance in Induction Cycle 2
NCT00602667 (62) [back to overview]Methotrexate Clearance in Induction Cycle 1
NCT00602667 (62) [back to overview]Methotrexate AUC0-66h in Induction Cycle 4
NCT00602667 (62) [back to overview]Methotrexate AUC0-66h in Induction Cycle 3
NCT00602667 (62) [back to overview]Methotrexate AUC0-66h in Induction Cycle 2
NCT00602667 (62) [back to overview]Methotrexate AUC0-66h in Induction Cycle 1
NCT00602667 (62) [back to overview]Feasibility and Toxicity of Administering Vinblastine With Induction Chemotherapy for Patients With Metastatic Disease as Measured by the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity
NCT00603538 (10) [back to overview]Number of Participants With Objective Response
NCT00603538 (10) [back to overview]Area Under the Plasma Concentration Curve From Time Zero to Tau (AUCtau)
NCT00603538 (10) [back to overview]Area Under the Plasma Concentration-time Curve From Time 0 to Day 22 (AUC0-day22)
NCT00603538 (10) [back to overview]Number of Participants With Positive Anti-Drug Antibody (ADA) Specific to CP-751,871 Following an Intravenous Infusion of CP-751,871.
NCT00603538 (10) [back to overview]Observed Accumulation Ratio (Rac)
NCT00603538 (10) [back to overview]Plasma Decay Half-Life (t1/2)
NCT00603538 (10) [back to overview]Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1)
NCT00603538 (10) [back to overview]Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3)
NCT00603538 (10) [back to overview]Number of Participants With Dose Limiting Toxicities (DLT)
NCT00603538 (10) [back to overview]Maximum Observed Concentration (Cmax) of CP-751,871
NCT00603915 (2) [back to overview]Progression Free Survival.
NCT00603915 (2) [back to overview]Number of Participants With the Responses Outlined
NCT00604461 (2) [back to overview]Number of Months of Progression Free Survival (PFS)
NCT00604461 (2) [back to overview]Number of Participants With Partial Response (PR) of Target Lesions
NCT00607048 (12) [back to overview]Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax
NCT00607048 (12) [back to overview]Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)
NCT00607048 (12) [back to overview]Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax)
NCT00607048 (12) [back to overview]Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax
NCT00607048 (12) [back to overview]Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX
NCT00607048 (12) [back to overview]Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax
NCT00607048 (12) [back to overview]Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax
NCT00607048 (12) [back to overview]Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax
NCT00607048 (12) [back to overview]Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX)
NCT00607048 (12) [back to overview]Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
NCT00607048 (12) [back to overview]Maximum Observed Serum Concentration (Cmax)
NCT00607048 (12) [back to overview]Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
NCT00608972 (5) [back to overview]Clinical Benefit Rate (CBR=CR+PR+SD)
NCT00608972 (5) [back to overview]Median Overall Survival After Treatment With Doxil, Carboplatin and Bevacizumab in Patients With ER, PR, HER2neu Negative
NCT00608972 (5) [back to overview]One-year Progression-free Survival
NCT00608972 (5) [back to overview]Progression Free Survival (PFS) After Treatment With Doxil, Carboplatin and Bevacizumab in Patients With ER, PR, HER2neu Negative Metastatic Breast Cancer
NCT00608972 (5) [back to overview]Six-month Survival After Treatment With Doxil, Carboplatin and Bevacizumab in Patients With ER, PR, HER2neu Negative
NCT00610714 (3) [back to overview]Progression-free Survival (PFS) as Evaluated by RECIST
NCT00610714 (3) [back to overview]Objective Response Rate as Evaluated by Response Evaluation Criteria In Solid Tumors ( RECIST)
NCT00610714 (3) [back to overview]Overall Survival (Number of Deaths)
NCT00614484 (2) [back to overview]Treatment Related Toxicities.
NCT00614484 (2) [back to overview]Overall Survival.
NCT00614822 (4) [back to overview]Number of Participants With Complete and Partial Tumor Responses
NCT00614822 (4) [back to overview]Number of Participants With Adverse Events
NCT00614822 (4) [back to overview]Progression Free Survival
NCT00614822 (4) [back to overview]Overall Survival
NCT00616967 (8) [back to overview]Number of Participants Who Experience Death During Treatment
NCT00616967 (8) [back to overview]Absolute Change From Baseline in Ki-67
NCT00616967 (8) [back to overview]Change in Standard Uptake Value (SULmax) From Baseline to Day 15 on FDG-PET
NCT00616967 (8) [back to overview]Cumulative Methylation Index (CMI) at Day 15
NCT00616967 (8) [back to overview]Change in Cumulative Methylation Index (CMI)
NCT00616967 (8) [back to overview]Safety as Measured by Number of Participants Who Experience Adverse Events
NCT00616967 (8) [back to overview]Pathological Complete Response (pCR) Rate
NCT00616967 (8) [back to overview]Number of Participants With Clinical Complete Response (cCR)
NCT00617942 (2) [back to overview]Number of Patients With Complete Pathologic Response Rate, Observed Following Treatment With q3week Carboplatin, Weekly Abraxane and Weekly Trastuzumab in Resectable and Unresectable LABC;
NCT00617942 (2) [back to overview]Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity
NCT00618657 (3) [back to overview]Progression Free Survival
NCT00618657 (3) [back to overview]Number of Participants With Toxicity of the Combinations in HER2 Positive and HER2 Negative Breast Cancer Assessed Using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0
NCT00618657 (3) [back to overview]Number of Participants With no Evidence of Microscopic pCR in the Neoadjuvant Setting
NCT00618917 (5) [back to overview]Overall Survival (OS)
NCT00618917 (5) [back to overview]Overall (Objective) Response
NCT00618917 (5) [back to overview]Time to Disease Progression
NCT00618917 (5) [back to overview]Radiation-induced Esophageal Toxicity
NCT00618917 (5) [back to overview]Determination of Recommended Phase II Dose of MnSOD/Plasmid DNA
NCT00621049 (4) [back to overview]Safety
NCT00621049 (4) [back to overview]Overall Survival (OS)
NCT00621049 (4) [back to overview]Disease-free Survival
NCT00621049 (4) [back to overview]2-year Survival
NCT00626405 (3) [back to overview]Tumor Response Rate, Calculated as a Percentage Along With it's 95% Confidence Interval
NCT00626405 (3) [back to overview]Progression-free Survival at 6 Months
NCT00626405 (3) [back to overview]Overall Survival
NCT00632853 (1) [back to overview]Overall Survival Time
NCT00634244 (2) [back to overview]The Rate of Treatment Failure
NCT00634244 (2) [back to overview]The Rate of Complete Remission (CR+CRi)
NCT00642759 (4) [back to overview]6 Month Survival Rate
NCT00642759 (4) [back to overview]Objective Response Rate to Carboplatin, Abraxane and Avastin
NCT00642759 (4) [back to overview]Overall Survival
NCT00642759 (4) [back to overview]6-month Progression Free Survival Rate
NCT00648648 (7) [back to overview]Mean Urine Excretion of MK-1775 24 Hours After the Day 1 Monotherapy Dose
NCT00648648 (7) [back to overview]Percentage of Total pCDC2 in Skin Cells at Baseline and 48 Hours After MK-1775 Dosing
NCT00648648 (7) [back to overview]Percentage of Total pCDC2 in Skin Cells at Baseline and 24 Hours After MK-1775 Dosing
NCT00648648 (7) [back to overview]Percentage of Total Cyclin-dependent Kinase (CDC2)-Positive Cells That Were Phosphorylated (pCDC2) in Skin Cells at Baseline and 8 Hours After MK-1775 Dosing
NCT00648648 (7) [back to overview]Best Overall Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
NCT00648648 (7) [back to overview]Plasma Concentration of MK-1775 at 8 Hours After Administration (C8hr) of Single or Multiple Oral Doses
NCT00648648 (7) [back to overview]Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
NCT00653068 (4) [back to overview]Overall Survival (OS)
NCT00653068 (4) [back to overview]Toxic Death
NCT00653068 (4) [back to overview]Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy
NCT00653068 (4) [back to overview]Event-free Survival
NCT00653939 (6) [back to overview]Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)
NCT00653939 (6) [back to overview]Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population
NCT00653939 (6) [back to overview]Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population
NCT00653939 (6) [back to overview]Progression Free Survival (PFS) in the Intent-to-Treat Population
NCT00653939 (6) [back to overview]Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)
NCT00653939 (6) [back to overview]Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)
NCT00654836 (3) [back to overview]Response Rate at End of Treatment
NCT00654836 (3) [back to overview]Progression-free Survival
NCT00654836 (3) [back to overview]Overall Survival
NCT00661193 (2) [back to overview]Response Rate (Confirmed and Unconfirmed, Complete and Partial Response) in a Subset of Patients With Measurable Disease
NCT00661193 (2) [back to overview]Selection of One of Two Treatment Regimens (Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel) for Further Study in a Phase III Trial, Based on Median Progression-free Survival for ≥ 3 Months
NCT00664105 (4) [back to overview]Overall Response Rate
NCT00664105 (4) [back to overview]Overall Survival
NCT00664105 (4) [back to overview]Time to Disease Progression
NCT00664105 (4) [back to overview]Number of Participants With Adverse Events by Grade
NCT00675259 (4) [back to overview]Number of Patients With Pathologic Complete Response (pCR)
NCT00675259 (4) [back to overview]Evaluation of Dynamic Contrast-enhanced Magnetic Resonance Imaging in Assessing pCR at Baseline and After 2 Cycles of Neoadjuvant Therapy
NCT00675259 (4) [back to overview]Overall Expression of LZTS1 Before and After Neoadjuvant Therapy as Assessed by Immunohistochemistry
NCT00675259 (4) [back to overview]Side Effects of Weekly Nab-paclitaxel, Carboplatin and Bevacizumab
NCT00683904 (15) [back to overview]Number of Participants With Dose-limiting Toxicity (DLT)
NCT00683904 (15) [back to overview]Number of Participants at Each Response Evaluation Criteria in Solid Tumors (RECIST) Assessment
NCT00683904 (15) [back to overview]Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose of Carboplatin in Combination With Ixabepilone, 32 mg/m^2
NCT00683904 (15) [back to overview]Maximum Observed Plasma Concentration of Ixabepilone
NCT00683904 (15) [back to overview]Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time of Ixabepilone
NCT00683904 (15) [back to overview]Number of Participants With Death as Outcome, Treatment-related Serious Adverse Events (SAEs), SAEs, Adverse Events (AEs), and Treatment-related AEs Leading to Discontinuation
NCT00683904 (15) [back to overview]Number of Participants With Grade 3 or Greater Treatment-related AEs
NCT00683904 (15) [back to overview]Number of Participants With Abnormalities in Blood Pressure and Heart Rate
NCT00683904 (15) [back to overview]Number of Participants With Abnormalities in Weight and Eastern Cooperative Oncology Group (ECOG) Performance Status
NCT00683904 (15) [back to overview]Number of Participants With Abnormalities in Urine Testing Results by Worst CTC Grade
NCT00683904 (15) [back to overview]Number of Participants With Abnormalities in Serum Chemistry Laboratory Values by Worst CTC Grade
NCT00683904 (15) [back to overview]Number of Participants With Abnormalities in Hematology Laboratory Values by Worst CTC Grade
NCT00683904 (15) [back to overview]Volume of Distribution at Steady State of Ixabepilone
NCT00683904 (15) [back to overview]Total Body Clearance of Ixabepilone
NCT00683904 (15) [back to overview]Time of Maximum Observed Plasma Concentration of Ixabepilone
NCT00686959 (7) [back to overview]Percentage of Participants With a Post Baseline Swallowing Diary Score >=4
NCT00686959 (7) [back to overview]Overall Survival
NCT00686959 (7) [back to overview]Objective Response Rate (Complete Response [CR] + Partial Response [PR])
NCT00686959 (7) [back to overview]Progression-free Survival (PFS)
NCT00686959 (7) [back to overview]Adverse Events: The Number of Deaths Per Treatment Group
NCT00686959 (7) [back to overview]Survival Rates at 1, 2, and 3 Years
NCT00686959 (7) [back to overview]First Site of Disease Failure in Terms of Relapse
NCT00687297 (3) [back to overview]Objective Response Rate
NCT00687297 (3) [back to overview]Progression-free Survival
NCT00687297 (3) [back to overview]Progression-free Survival
NCT00695292 (5) [back to overview]Time to Progression
NCT00695292 (5) [back to overview]Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
NCT00695292 (5) [back to overview]Number of Participants Experiencing Treatment Related Toxicity
NCT00695292 (5) [back to overview]Median Overall Survival
NCT00695292 (5) [back to overview]One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment
NCT00698451 (2) [back to overview]The Primary Efficacy End Point is the Number of Patients With an Objective Response.
NCT00698451 (2) [back to overview]The Secondary Efficacy Endpoints is Duration of Objective Response.
NCT00700180 (9) [back to overview]Percentage of Participants With Measurable Disease at Baseline Who Achieved CR, PR, or Stable Disease (SD) for at Least 6 Weeks
NCT00700180 (9) [back to overview]Overall Survival - Time to Event
NCT00700180 (9) [back to overview]Duration of Response - Time to Event
NCT00700180 (9) [back to overview]Duration of Response - Percentage of Participants With an Event
NCT00700180 (9) [back to overview]Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level
NCT00700180 (9) [back to overview]Overall Survival - Percentage of Participants With an Event
NCT00700180 (9) [back to overview]Progression-Free Survival - Time to Event
NCT00700180 (9) [back to overview]Progression-Free Survival - Percentage of Participants With an Event
NCT00700180 (9) [back to overview]Percentage of Participants With Objective Response
NCT00712582 (2) [back to overview]Overall Survival at 1 Year
NCT00712582 (2) [back to overview]2-year PFS From the Start of Induction Therapy Conditional
NCT00723125 (2) [back to overview]Number of Participants With Adverse Events
NCT00723125 (2) [back to overview]Pathological Complete Response Rates at Surgery
NCT00723957 (9) [back to overview]Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors
NCT00723957 (9) [back to overview]Median Length of Survival in the Overall Population and in the Subgroups of Patients With βIII-tubulin Positive (β3T+) and βIII-tubulin Negative (β3T-)Tumors
NCT00723957 (9) [back to overview]Time to Response
NCT00723957 (9) [back to overview]Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR)
NCT00723957 (9) [back to overview]Number of Participants With Hematology Laboratory Results of Grade 3 or 4
NCT00723957 (9) [back to overview]Progression-free Survival in the Overall Population
NCT00723957 (9) [back to overview]Number of Participants With Death as Outcome, Drug-related Adverse Events (AEs), Serious AEs (SAEs), Drug-related SAEs, AEs Leading to Discontinuation, and Drug-related Peripheral Neuropathy
NCT00723957 (9) [back to overview]Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results
NCT00723957 (9) [back to overview]Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors
NCT00729612 (4) [back to overview]Progression Free Survival
NCT00729612 (4) [back to overview]Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0
NCT00729612 (4) [back to overview]Overall Response Rate Defined as Complete or Partial Response as Assessed by RECIST Version 1.0 Criteria.
NCT00729612 (4) [back to overview]Overall Survival
NCT00735696 (9) [back to overview]Summary of Participants Reporting Adverse Events
NCT00735696 (9) [back to overview]Duration of Response
NCT00735696 (9) [back to overview]Serum Anti-Ramucirumab Antibody Assessment
NCT00735696 (9) [back to overview]Maximum Concentration of Ramucirumab (Cmax)
NCT00735696 (9) [back to overview]Overall Survival (OS)
NCT00735696 (9) [back to overview]Overall Survival (OS) at 1 Year
NCT00735696 (9) [back to overview]Percentage of Participants Who Are Progression-free (PFS) at 6 Months
NCT00735696 (9) [back to overview]Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate ([ORR])
NCT00735696 (9) [back to overview]Progression-free Survival (PFS)
NCT00735878 (4) [back to overview]Number of Patients With Buccal Cells Demonstrating a Decline in Cyclin D1
NCT00735878 (4) [back to overview]Objective Response Rate of Participants Using A Combination of ABT-751 and Carboplatin
NCT00735878 (4) [back to overview]Maximum Tolerated Dose (MTD) of ABT-751 in Combination With Carboplatin
NCT00735878 (4) [back to overview]The Median Survival in the Study Population
NCT00737243 (2) [back to overview]Number of Participants With a Tissue of Origin Successfully Predicted by the Assay
NCT00737243 (2) [back to overview]Overall Survival
NCT00741988 (4) [back to overview]Progression Free Survival, the Length of Time, That Patients Were Alive From Their First Date of Treatment Until Worsening of Their Disease
NCT00741988 (4) [back to overview]Number of Participants Experiencing Treatment Related Toxicity
NCT00741988 (4) [back to overview]Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death
NCT00741988 (4) [back to overview]Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
NCT00762034 (28) [back to overview]Translational Research: Overall Survival (OS) Based on Cytoplasmic and Nuclear Thymidylate Synthase (TS) Expression
NCT00762034 (28) [back to overview]Translational Research: Overall Survival (OS) Based on Cytoplasmic and Membrane Folate Receptor Alpha (FR-α) Expression
NCT00762034 (28) [back to overview]Translational Research: Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) Bevacizumab
NCT00762034 (28) [back to overview]Percentage of Participants With a Complete Response (CR) and Partial Response (PR) (Overall Response Rate)
NCT00762034 (28) [back to overview]Overall Survival
NCT00762034 (28) [back to overview]Number of Participants Who Received a Transfusion
NCT00762034 (28) [back to overview]Number of Participants Receiving Concomitant Medication
NCT00762034 (28) [back to overview]Percentage of Participants With a Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate)
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Pemetrexed Clearance (CL)
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Bevacizumab Clearance (CL)
NCT00762034 (28) [back to overview]Safety and Toxicity Profile of Study Treatments
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Platinum Clearance (CL) for Total (Bound and Unbound) and Unbound Forms
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Pemetrexed
NCT00762034 (28) [back to overview]Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity (FACT/GOG-Ntx)
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Total (Bound and Unbound) Platinum and Unbound Platinum
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Total (Bound and Unbound) Platinum and Unbound Platinum
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Bevacizumab
NCT00762034 (28) [back to overview]Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - General (FACT-G)
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Elimination Half-life (t1/2) for Bevacizumab
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Elimination Half-life (t1/2) for Pemetrexed
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Pemetrexed
NCT00762034 (28) [back to overview]Duration of Hospitalizations Per Participant
NCT00762034 (28) [back to overview]Time to Progressive Disease
NCT00762034 (28) [back to overview]Translational Research: Overall Survival (OS) Based on Nuclear Thyroid Transcription Factor-1 (TTF-1) Expression Regardless of Study Treatment
NCT00762034 (28) [back to overview]Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - Lung (FACT-L)
NCT00762034 (28) [back to overview]Progression Free Survival Time
NCT00762034 (28) [back to overview]Pharmacokinetics (PK): Elimination Half-life (t1/2) for Total (Bound and Unbound) Platinum and Unbound Platinum
NCT00780494 (4) [back to overview]Progression-Free Survival (PFS)
NCT00780494 (4) [back to overview]Overall Survival (OS)
NCT00780494 (4) [back to overview]Adverse Events ≥ Grade 3 and Related to Bevacizumab
NCT00780494 (4) [back to overview]Objective (Overall) Therapeutic Response
NCT00788125 (1) [back to overview]Maximum Administered Dose of Dasatinib (Phase I)
NCT00795340 (3) [back to overview]Overall Survival
NCT00795340 (3) [back to overview]Objective Tumor Response as Assessed by RECIST Criteria v1.1.
NCT00795340 (3) [back to overview]Progression-free Survival
NCT00796991 (31) [back to overview]Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
NCT00796991 (31) [back to overview]Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
NCT00796991 (31) [back to overview]Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population
NCT00796991 (31) [back to overview]Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population
NCT00796991 (31) [back to overview]Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population
NCT00796991 (31) [back to overview]Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population
NCT00796991 (31) [back to overview]Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population
NCT00796991 (31) [back to overview]Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants
NCT00796991 (31) [back to overview]Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population
NCT00796991 (31) [back to overview]Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population
NCT00796991 (31) [back to overview]Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants
NCT00796991 (31) [back to overview]Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population
NCT00796991 (31) [back to overview]Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 5 in Neuropathy Assessed by Treatment-specific Adverse Events Scale
NCT00798603 (17) [back to overview]Proportion of Confirmed Tumor Response Defined as an Objective Status of Complete Response or Partial Response on Two Consecutive Evaluations
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 3 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 3 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 3 in Nausea Assessed by Treatment-specific Adverse Events Scale
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 5 in Fatigue Assessed by Treatment-specific Adverse Events Scale
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 5 in Nausea Assessed by Treatment-specific Adverse Events Scale
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 3 in Fatigue Assessed by Treatment-specific Adverse Events Scale
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 5 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 3 in Neuropathy Assessed by Treatment-specific Adverse Events Scale
NCT00798603 (17) [back to overview]Progression-free Survival
NCT00798603 (17) [back to overview]Number of Grade 3 or Higher Adverse Events Occurring in >=10% of Patients
NCT00798603 (17) [back to overview]Overall Survival
NCT00798603 (17) [back to overview]Progression-free Survival at 6 Months
NCT00798603 (17) [back to overview]Duration of Response
NCT00798603 (17) [back to overview]Change From Baseline to Cycle 5 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale
NCT00798603 (17) [back to overview]Time to Treatment Failure
NCT00800202 (7) [back to overview]Probability of Being Alive at 12 and 18 Months
NCT00800202 (7) [back to overview]Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months
NCT00800202 (7) [back to overview]Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECIST
NCT00800202 (7) [back to overview]Percentage of Participants Who Died
NCT00800202 (7) [back to overview]Percentage of Participants With Disease Progression or Death
NCT00800202 (7) [back to overview]Time to Death
NCT00800202 (7) [back to overview]Time to Disease Progression or Death
NCT00806286 (5) [back to overview]Percentage of Participants With Progression-Free Survival Based on Radiologic and Clinical Assessments and Death After Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Percentage of Participants With Progression-Free Survival at 18 Weeks Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Summary of Kaplan-Meier Analysis of Overall Survival Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Number of Participants With Best Overall Tumor Response and Objective Response Rate Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00806286 (5) [back to overview]Number of Participants With Treatment-Emergent Adverse Events Related to CS-7017/Placebo Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer
NCT00807768 (6) [back to overview]Number of Participants With Recurrence or Death Events at Primary Analysis
NCT00807768 (6) [back to overview]Number of Participants With Sites of Recurrence
NCT00807768 (6) [back to overview]Patient Reported Fatigue
NCT00807768 (6) [back to overview]Patient-reported Neurotoxicity
NCT00807768 (6) [back to overview]Patient-reported Quality of Life
NCT00807768 (6) [back to overview]Number of Participants With Death Events
NCT00809133 (24) [back to overview]Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.
NCT00809133 (24) [back to overview]Part D: Carboplatin Cmax in Cycle 1 and 2
NCT00809133 (24) [back to overview]Part D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2
NCT00809133 (24) [back to overview]Part D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2
NCT00809133 (24) [back to overview]Part C: Carboplatin Cmax in Cycle 1 and Cycle 2
NCT00809133 (24) [back to overview]Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)
NCT00809133 (24) [back to overview]Maximum Tolerated Dose (MTD)
NCT00809133 (24) [back to overview]Part D: Paclitaxel Cmax in Cycle 1 and 2
NCT00809133 (24) [back to overview]Part A: Afatinib Cmax,ss on Day 15
NCT00809133 (24) [back to overview]Part D: Afatinib Cmax,ss
NCT00809133 (24) [back to overview]Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2
NCT00809133 (24) [back to overview]Objective Tumour Response (Confirmed)
NCT00809133 (24) [back to overview]Incidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade
NCT00809133 (24) [back to overview]Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15
NCT00809133 (24) [back to overview]Part B: Afatinib Cmax,ss on Day 15
NCT00809133 (24) [back to overview]Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15
NCT00809133 (24) [back to overview]Part C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2
NCT00809133 (24) [back to overview]Part B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15
NCT00809133 (24) [back to overview]Part B: Bevacizumab Plasma Concentration
NCT00809133 (24) [back to overview]Part C: Afatinib Cmax,ss in Cycle 2
NCT00809133 (24) [back to overview]Part A: Paclitaxel Cmax on Day 1 and Day 15
NCT00809133 (24) [back to overview]Part A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15
NCT00809133 (24) [back to overview]Objective Tumour Response (Unconfirmed)
NCT00809133 (24) [back to overview]Part B: Paclitaxel Cmax on Day 1 and Day 15
NCT00820872 (1) [back to overview]Proportion of Patients Experiencing Grade 3 or 4 Diarrhea as Measured by NCI CTCAE v3.0
NCT00821886 (4) [back to overview]Overall Survival
NCT00821886 (4) [back to overview]Pathologic Complete Response (pCR)
NCT00821886 (4) [back to overview]Number of Subjects With Adverse Events as a Measure of Safety and Toxicity
NCT00821886 (4) [back to overview]Disease-free Survival
NCT00828009 (3) [back to overview]Overall Survival
NCT00828009 (3) [back to overview]Proportion of Patients With Target Adverse Events for the Step 2 Treatment
NCT00828009 (3) [back to overview]Progression-free Survival
NCT00828841 (3) [back to overview]Overall Survival by Treatment Arm
NCT00828841 (3) [back to overview]Overall Survival by Histology
NCT00828841 (3) [back to overview]1-year Survival by Treatment Arm
NCT00832819 (1) [back to overview]Maximum Tolerated Dose (MTD)
NCT00848718 (12) [back to overview]Maximum Plasma Concentration of MK-2206 (Cmax)
NCT00848718 (12) [back to overview]Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel
NCT00848718 (12) [back to overview]Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1
NCT00848718 (12) [back to overview]Minimum Plasma Concentration of MK-2206 (Ctrough)
NCT00848718 (12) [back to overview]MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel
NCT00848718 (12) [back to overview]Time to Maximum Plasma Concentration of MK-2206 (Tmax)
NCT00848718 (12) [back to overview]MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib
NCT00848718 (12) [back to overview]MTD of MK-2206 Administered Q3W in Combination With Docetaxel
NCT00848718 (12) [back to overview]MTD of MK-2206 Administered QOD in Combination With Docetaxel
NCT00848718 (12) [back to overview]MTD of MK-2206 Administered QOD in Combination With Erlotinib
NCT00848718 (12) [back to overview]Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)
NCT00848718 (12) [back to overview]Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)
NCT00849667 (22) [back to overview]Progression-free Survival (PFS)
NCT00849667 (22) [back to overview]Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria
NCT00849667 (22) [back to overview]AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]CL: Clearance of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]Time to Tumor Response (TTR)
NCT00849667 (22) [back to overview]CL: Clearance of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel
NCT00849667 (22) [back to overview]Time to 50% Serologic Response (TSR)
NCT00849667 (22) [back to overview]Percentage of Participants With Objective Response
NCT00849667 (22) [back to overview]Percentage of Participants With Length of Second Remission Greater Than First Remission
NCT00849667 (22) [back to overview]Percentage of Participants With Clinical Benefit
NCT00849667 (22) [back to overview]Overall Survival (OS)
NCT00849667 (22) [back to overview]Duration of Tumor Response
NCT00849667 (22) [back to overview]Duration of 50% Serologic Response
NCT00849667 (22) [back to overview]Cancer Antigen-125 (CA-125) Progression-Free Survival
NCT00849667 (22) [back to overview]Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores
NCT00849667 (22) [back to overview]Percentage of Participants With Serologic Response (SR)
NCT00849667 (22) [back to overview]Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel
NCT00856830 (3) [back to overview]Number of Patients With Adverse Events - Phase II
NCT00856830 (3) [back to overview]Progression Free Survival
NCT00856830 (3) [back to overview]Number of Participants Experiencing Dose Limiting Toxicity Regimen A - Phase I
NCT00861705 (7) [back to overview]Overall Survival
NCT00861705 (7) [back to overview]Incidence and Severity of Post-op Complications, Namely Excessive Bleeding, Delayed Wound Healing, and Wound Dehiscence.
NCT00861705 (7) [back to overview]Pathologic Complete Response (pCR) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is).
NCT00861705 (7) [back to overview]Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0).
NCT00861705 (7) [back to overview]Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0).
NCT00861705 (7) [back to overview]Pathologic Complete Response (pCR) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is).
NCT00861705 (7) [back to overview]Pathologic Stage in the Breast and in the Breast Plus Axilla as Measured by American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) Staging Criteria (Version 6)
NCT00870870 (6) [back to overview]Number of Participants With Adverse Events (AEs) or Deaths
NCT00870870 (6) [back to overview]Time To Progression (TTP)
NCT00870870 (6) [back to overview]Progression-Free Survival (PFS)
NCT00870870 (6) [back to overview]Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
NCT00870870 (6) [back to overview]Overall Survival (OS)
NCT00870870 (6) [back to overview]Duration of Response
NCT00873119 (6) [back to overview]Overall Survival (OS)
NCT00873119 (6) [back to overview]Progression Free Survival
NCT00873119 (6) [back to overview]Best Overall Response
NCT00873119 (6) [back to overview]Duration of Response
NCT00873119 (6) [back to overview]Time to Response
NCT00873119 (6) [back to overview]Time to Progression (TTP)
NCT00874848 (6) [back to overview]Duration of Time to Progression (TTP) in Each Study Arm Based on Independent Central Radiology Review
NCT00874848 (6) [back to overview]Disease Control Rate (DCR) in Each Study Arm Based on Independent Central Radiology Review
NCT00874848 (6) [back to overview]Duration of Objective Tumor Response in Each Study Arm Based on Independent Central Radiology Review
NCT00874848 (6) [back to overview]Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Rates in Each Study Arm Based on Independent Central Radiology Review
NCT00874848 (6) [back to overview]Overall Survival (OS) in Each Study Arm Based on the Safety Population
NCT00874848 (6) [back to overview]Objective Response Rate (ORR) in Each Study Arm Based on Independent Central Radiology Review
NCT00875615 (2) [back to overview]Number of Subjects Experiencing Adverse Events
NCT00875615 (2) [back to overview]Number of Patients Achieving Clinical Benefit
NCT00879359 (2) [back to overview]Median Progression Free Survival of This Treatment Regimen in Patients With Advanced/Recurrent Endometrial Cancer.
NCT00879359 (2) [back to overview]Number of Participants With Adverse Events Grades 1-5
NCT00883675 (1) [back to overview]Febrile Neutropenia
NCT00883779 (16) [back to overview]Time to Deterioration in TOI Using FACT-L Version 4.0
NCT00883779 (16) [back to overview]Time to Progression
NCT00883779 (16) [back to overview]Time to Symptomatic Progression
NCT00883779 (16) [back to overview]Median Overall Survival (OS) Time-Overall and Among Different Subgroups
NCT00883779 (16) [back to overview]Median PFS Time Based on Different Subgroups
NCT00883779 (16) [back to overview]Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups
NCT00883779 (16) [back to overview]Percentage of Participants With Symptomatic Progression Assessed Using the Lung Cancer Subscale (LCS)
NCT00883779 (16) [back to overview]Duration of Response
NCT00883779 (16) [back to overview]Median Follow-up Time During the Study
NCT00883779 (16) [back to overview]Median Progression Free Survival (PFS) Time
NCT00883779 (16) [back to overview]Non-Progression Rate: Percentage of Participants With a Confirmed Best Overall Response of Either Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for At Least 16 Weeks
NCT00883779 (16) [back to overview]Objective Response Rate: Percentage of Participants With a Confirmed Best Overall Response of CR or PR
NCT00883779 (16) [back to overview]Percentage of Participants Alive and Free From Disease Progression
NCT00883779 (16) [back to overview]Percentage of Participants With Deterioration in Quality of Life (QOL) Using FACT-L Version 4.0
NCT00883779 (16) [back to overview]Percentage of Participants With Deterioration in Trial Outcome Index (TOI) Using FACT-L Version 4.0
NCT00883779 (16) [back to overview]Time to Deterioration in QOL Using FACT-L Version 4.0
NCT00887575 (5) [back to overview]Number of Participants With Adverse Events as a Measure of Safety and Tolerability
NCT00887575 (5) [back to overview]Overall Survival (OS)
NCT00887575 (5) [back to overview]Overall Response Rate (ORR)
NCT00887575 (5) [back to overview]Phase II: The Number of Subjects Exhibiting Pathologic Complete Response to Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin
NCT00887575 (5) [back to overview]Disease-free Survival
NCT00892710 (6) [back to overview]Overall Survival (OS)
NCT00892710 (6) [back to overview]Overall Response Rate (ORR), the Number of Patients Who Experience an Objective Benefit From Treatment
NCT00892710 (6) [back to overview]Progression Free Survival (PFS)
NCT00892710 (6) [back to overview]Time to Progression (TTP)
NCT00892710 (6) [back to overview]Time to Treatment Failure (TTTF)
NCT00892710 (6) [back to overview]6-month and 12-month Overall Survival Probability
NCT00894504 (4) [back to overview]Objective Response Rate and Clinical Benefit Rate
NCT00894504 (4) [back to overview]Correlation of Biomarker Expressions of EGFR, K-ras, p53, PTEN Expression, and PI3K in Triple-negative Breast Cancer With Response to Treatment With the Combination of Gemcitabine, Carboplatin, and Panitumumab
NCT00894504 (4) [back to overview]Progression-free Survival (PFS)
NCT00894504 (4) [back to overview]Number of Treatment-related Toxicities Occurring in ≥10% of Patients as a Measure of Tolerability and Toxicity
NCT00896181 (5) [back to overview]Number of Participants With Treatment Response
NCT00896181 (5) [back to overview]Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy
NCT00896181 (5) [back to overview]Median Progression-free Survival (PFS)
NCT00896181 (5) [back to overview]Number of Participants With Adverse Events Resulting in Treatment Discontinuation
NCT00896181 (5) [back to overview]Overall Survival (OS)
NCT00906282 (5) [back to overview]3-Year Overall Survival Rate
NCT00906282 (5) [back to overview]Rate of Residual Disease as an Assessment of Pathological Partial Response (pPR)
NCT00906282 (5) [back to overview]Objective Tumor Response
NCT00906282 (5) [back to overview]Pathologic Response Rate
NCT00906282 (5) [back to overview]Complete Resection Rate
NCT00910000 (3) [back to overview]Vorinostat Maximum Tolerated Dose (MTD) [Phase Ib]
NCT00910000 (3) [back to overview]Response
NCT00910000 (3) [back to overview]Dose Limiting Toxicity (DLT) [Phase Ib]
NCT00915005 (2) [back to overview]The Incidence and Time to Development of Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) Grade > 3 Treatment-related Pneumonitis (TRP)
NCT00915005 (2) [back to overview]The Incidence and Time to Development of Local Failure (LF)
NCT00918203 (12) [back to overview]Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)
NCT00918203 (12) [back to overview]PK - Maximum Concentration (Cmax) of Olaratumab
NCT00918203 (12) [back to overview]PK - Half-Life (t1/2) of Olaratumab
NCT00918203 (12) [back to overview]PK - Clearance (Cl) of Olaratumab
NCT00918203 (12) [back to overview]Pharmacokinetics (PK) - Area Under the Curve (AUC) 0-168 of Olaratumab
NCT00918203 (12) [back to overview]Percentage of Participants With Anti-Olaratumab Antibodies
NCT00918203 (12) [back to overview]Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR)
NCT00918203 (12) [back to overview]Overall Survival (OS)
NCT00918203 (12) [back to overview]Median Duration of Response
NCT00918203 (12) [back to overview]Safety and Tolerability of Olaratumab Administered at a More Rapid Rate (25mg/Min With Minimum Infusion Time of 30 Minutes), Determined by Number of Participants With Treatment Related Adverse Events
NCT00918203 (12) [back to overview]Progression-Free Survival (PFS)
NCT00918203 (12) [back to overview]PK - Steady State Volume of Distribution (Vss) of Olaratumab
NCT00927589 (19) [back to overview]Baseline-adjusted QTcF, QTcB, PR Interval, and QRS Duration
NCT00927589 (19) [back to overview]Baseline-adjusted Heart Rate
NCT00927589 (19) [back to overview]Area Under the Curve From Time Zero to 6 Hours Post Infusion (AUC0-6hr) of Carboplatin
NCT00927589 (19) [back to overview]Geometric Mean Ratio of Cmax/D of Carboplatin
NCT00927589 (19) [back to overview]Geometric Mean Ratio of AUC0-6hr/D of Carboplatin
NCT00927589 (19) [back to overview]Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State
NCT00927589 (19) [back to overview]Change From Baseline in Corrected QT Interval Using Bazett's Correction (QTcB) at Trastuzumab Steady State
NCT00927589 (19) [back to overview]Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab
NCT00927589 (19) [back to overview]Plasma Decay Half-Life (t1/2) of Carboplatin
NCT00927589 (19) [back to overview]Number of Participants Within Each Absolute QTc Interval Category
NCT00927589 (19) [back to overview]Number of Participants With New Abnormal U Waves on ECG
NCT00927589 (19) [back to overview]Number of Participants With New Abnormal T Waves on ECG
NCT00927589 (19) [back to overview]Number of Participants With Increase From Baseline in QTc Interval
NCT00927589 (19) [back to overview]Number of Participants With Abnormal Changes in QRS Interval
NCT00927589 (19) [back to overview]Number of Participants With Abnormal Changes in PR Interval
NCT00927589 (19) [back to overview]Maximum Observed Serum Concentration (Cmax) of Trastuzumab
NCT00927589 (19) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Carboplatin
NCT00927589 (19) [back to overview]Dose-Normalized Cmax (Cmax/D) of Carboplatin
NCT00927589 (19) [back to overview]Dose-Normalized AUC0-6hr (AUC0-6hr/D) of Carboplatin
NCT00929162 (2) [back to overview]Tumour Response Rate
NCT00929162 (2) [back to overview]Progression Free Survival
NCT00936702 (5) [back to overview]Overall Survival
NCT00936702 (5) [back to overview]Time to Treatment Failure
NCT00936702 (5) [back to overview]Progression-free Survival
NCT00936702 (5) [back to overview]Percentage of Participants With Confirmed Tumor Responses
NCT00936702 (5) [back to overview]Duration of Response
NCT00937560 (5) [back to overview]Duration of Response
NCT00937560 (5) [back to overview]Progression-free Survival
NCT00937560 (5) [back to overview]Biological Progression-free Interval
NCT00937560 (5) [back to overview]Percentage of Participants With an Objective Response
NCT00937560 (5) [back to overview]Overall Survival at 1 Year and 2 Years
NCT00942357 (5) [back to overview]Patient-reported Peripheral Neuropathy Symptoms
NCT00942357 (5) [back to overview]Number of Participants With Late Adverse Events as Graded by the NCI CTCAE Version 3.0
NCT00942357 (5) [back to overview]Number of Participants With Recurrence, Progression or Death
NCT00942357 (5) [back to overview]Number of Participants With Acute Adverse Effects as Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version (CTCAE) Version 3.0
NCT00942357 (5) [back to overview]Patient-reported Quality of Life (QOL)
NCT00945191 (3) [back to overview]Best Overall Response and Objective Response Rate Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
NCT00945191 (3) [back to overview]Change From Baseline in the Sum of Longest Diameters of Target Lesions Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
NCT00945191 (3) [back to overview]Participants With Treatment-Emergent Adverse Events Grade 3 or Higher by System Organ Class and Preferred Term Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer
NCT00946712 (7) [back to overview]Overall Survival (OS) of EGFR FISH-positive Patients
NCT00946712 (7) [back to overview]Progression-free Survival (PFS) of EGFR FISH-positive Patients by Institutional Review
NCT00946712 (7) [back to overview]Progression-Free Survival (PFS) of the Entire Study Population by Institutional Review
NCT00946712 (7) [back to overview]Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in the Entire Study Population
NCT00946712 (7) [back to overview]Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs
NCT00946712 (7) [back to overview]Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in EGFR FISH-positive Patients
NCT00946712 (7) [back to overview]Overall Survival (OS) in the Entire Study Population
NCT00948675 (5) [back to overview]Disease Control Rates Defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD)
NCT00948675 (5) [back to overview]Overall Survival (OS)
NCT00948675 (5) [back to overview]Percentage of Participants With Complete Response or Partial Response (Overall Tumor Response Rate)
NCT00948675 (5) [back to overview]Progression Free Survival (PFS)
NCT00948675 (5) [back to overview]Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
NCT00951496 (7) [back to overview]Overall Survival
NCT00951496 (7) [back to overview]Patient Reported Nausea
NCT00951496 (7) [back to overview]Patient Reported Quality of Life (QOL)
NCT00951496 (7) [back to overview]Patient Reported Fatigue
NCT00951496 (7) [back to overview]Median Progression-free Survival
NCT00951496 (7) [back to overview]Patient Reported Neurotoxicity (Ntx)
NCT00951496 (7) [back to overview]Patients With Adverse Events by Treatment Group, as Defined by NCI CTCAE (Common Terminology Criteria for Adverse Events Version 3.0) Version 3.0
NCT00953121 (5) [back to overview]Objective Response Rate
NCT00953121 (5) [back to overview]6 Month Progression-free Survival
NCT00953121 (5) [back to overview]Median Overall Survival (OS)
NCT00953121 (5) [back to overview]Median Progression Free Survival (PFS)
NCT00953121 (5) [back to overview]Safety of Bevacizumab (Avastin) in Combination With Irinotecan and Carboplatin
NCT00954174 (7) [back to overview]Patient-Reported Quality of Life (QOL) - Baseline
NCT00954174 (7) [back to overview]Overall Survival
NCT00954174 (7) [back to overview]Patient Reported Peripheral Neuropathy Symptoms - Baseline
NCT00954174 (7) [back to overview]Patient Reported Quality of Life (QOL) - Post Baseline
NCT00954174 (7) [back to overview]Incidence of Adverse Events as Assessed by CTCAE Version 3.0
NCT00954174 (7) [back to overview]Patient-reported Peripheral Neuropathy Symptoms - Post Baseline
NCT00954174 (7) [back to overview]Duration of Progression-free Survival
NCT00954512 (2) [back to overview]Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response
NCT00954512 (2) [back to overview]Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs)
NCT00955305 (3) [back to overview]Proportion of Patients With Objective Response
NCT00955305 (3) [back to overview]Overall Survival (OS)
NCT00955305 (3) [back to overview]Progression-free Survival (PFS)
NCT00960297 (1) [back to overview]Number of Participants Experiencing Adverse Events as a Measure of Toxicity
NCT00967369 (4) [back to overview]Overall Survival (OS) Rate at 24 Months
NCT00967369 (4) [back to overview]Progression Free Survival (PFS) Rate at 12 Months
NCT00967369 (4) [back to overview]Overall Response After 3 Cycles of Botezomib Plus ICE (BICE) Versus Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma
NCT00967369 (4) [back to overview]PET Scan Response After 3 Cycles of BICE Versus ICE Chemotherapy.
NCT00971932 (7) [back to overview]Disease Control Rate
NCT00971932 (7) [back to overview]Overall Survival (OS) Time
NCT00971932 (7) [back to overview]Progression-Free Survival (PFS) Time
NCT00971932 (7) [back to overview]Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria
NCT00971932 (7) [back to overview]Duration of Response
NCT00971932 (7) [back to overview]Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
NCT00971932 (7) [back to overview]Time to Treatment Failure
NCT00976456 (2) [back to overview]Overall Survival
NCT00976456 (2) [back to overview]Progression Free Survival
NCT00976573 (4) [back to overview]Overall Survival Time
NCT00976573 (4) [back to overview]Confirmed Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
NCT00976573 (4) [back to overview]Toxicity
NCT00976573 (4) [back to overview]Progression-free Survival
NCT00976677 (1) [back to overview]Progression-free Survival (PFS)
NCT00977561 (1) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT00977574 (4) [back to overview]The Median Duration of Overall Survival for Each of the Three Arms.
NCT00977574 (4) [back to overview]The Proportion of Patients With Measurable Disease Who Have Confirmed Objective Tumor Responses by Treatment.
NCT00977574 (4) [back to overview]Number of Participants Who Progressed or Died by 25 Months From Enrollment
NCT00977574 (4) [back to overview]Frequency and Severity of Toxicity as Assessed by CTCAE v3.0 for Each of the Three Arms.
NCT00979212 (6) [back to overview]Mediastinal Nodal Clearance After Completion of Induction Chemoradiotherapy With or Without Panitumumab.
NCT00979212 (6) [back to overview]Percentage of Patients With Grade 3 or Higher Acute and Late Adverse Events
NCT00979212 (6) [back to overview]Patterns of First Failure
NCT00979212 (6) [back to overview]Surgical Morbidities in Patients With Resectable Disease at Reassessment
NCT00979212 (6) [back to overview]Response Rate
NCT00979212 (6) [back to overview]Overall Survival
NCT00986674 (3) [back to overview]Overall Survival
NCT00986674 (3) [back to overview]Response Rate
NCT00986674 (3) [back to overview]Progression Free Survival
NCT00993616 (3) [back to overview]Frequency and Severity of Observed Adverse Effects Graded According to NCI CTCAE Version 3.0
NCT00993616 (3) [back to overview]Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version 1.1)
NCT00993616 (3) [back to overview]Progression Free Survival at 6 Months
NCT00993655 (3) [back to overview]Overall Survival
NCT00993655 (3) [back to overview]9-month Progression Rate Post-randomization
NCT00993655 (3) [back to overview]Progression Free Survival
NCT00995007 (3) [back to overview]Progression Free Survival at 6 Months
NCT00995007 (3) [back to overview]Overall Survival
NCT00995007 (3) [back to overview]Number of Participants With Adverse Events
NCT01001910 (3) [back to overview]Overall Survival (OS)
NCT01001910 (3) [back to overview]Progression-free Interval
NCT01001910 (3) [back to overview]Incidence of Toxicities
NCT01004172 (5) [back to overview]CNS Best Response
NCT01004172 (5) [back to overview]Central Nervous System (CNS) Objective Response Rate
NCT01004172 (5) [back to overview]Overall Survival
NCT01004172 (5) [back to overview]Progression-Free Survival
NCT01004172 (5) [back to overview]Site of First Progression
NCT01005329 (6) [back to overview]Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 1 Year After Treatment Start
NCT01005329 (6) [back to overview]Pelvic Failure Rate (Two-year Rate Reported)
NCT01005329 (6) [back to overview]Overall Survival (Two-year Rate Reported)
NCT01005329 (6) [back to overview]Distant Failure (Two-year Rate Reported)
NCT01005329 (6) [back to overview]Disease-free Survival (Two-year Rate Reported)
NCT01005329 (6) [back to overview]Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 90 Days After Treatment Start
NCT01009346 (2) [back to overview]Progression Free Survival (PFS) of RAD001 in Combination With Weekly Cetuximab and Cisplatin.
NCT01009346 (2) [back to overview]Maximum Tolerated Dose (MTD) of RAD001 in Combination With Cetuximab and Cisplatin.
NCT01009515 (4) [back to overview]Time to Progression
NCT01009515 (4) [back to overview]Objective Response Rate (ORR)
NCT01009515 (4) [back to overview]Safety Profile
NCT01009515 (4) [back to overview]Overall Survival
NCT01009983 (3) [back to overview]Time to Progression
NCT01009983 (3) [back to overview]Survival
NCT01009983 (3) [back to overview]Antitumor Activity as Assessed by Objective Tumor Response According to RECIST Criteria
NCT01014351 (3) [back to overview]Overall Survival (OS)
NCT01014351 (3) [back to overview]Progression-free Survival (PFS)
NCT01014351 (3) [back to overview]Objective Response Rate (ORR)
NCT01015118 (9) [back to overview]Overall Survival
NCT01015118 (9) [back to overview]Objective Response Based on Investigator Assessment
NCT01015118 (9) [back to overview]Change in Global Health Status/ Quality of Life (QoL) Scale Over Time.
NCT01015118 (9) [back to overview]Change in Abdominal/Gastro-intestinal Symptoms Over Time
NCT01015118 (9) [back to overview]Time to CA-125 Tumour Marker Progression
NCT01015118 (9) [back to overview]PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint).
NCT01015118 (9) [back to overview]PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint - Follow up Analysis).
NCT01015118 (9) [back to overview]PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria.
NCT01015118 (9) [back to overview]PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria (Follow up Analysis).
NCT01016769 (4) [back to overview]Number of Participants With Potential Molecular Markers of Resistance to mTOR Inhibition
NCT01016769 (4) [back to overview]Number of Participants Who Experienced Adverse Events
NCT01016769 (4) [back to overview]Phase II Recommended Dose for the Combination of Temsirolimus + Weekly Paclitaxel + Carboplatin.
NCT01016769 (4) [back to overview]Median Overall Survival
NCT01020786 (9) [back to overview]Overall Survival (OS) During the Maintenance Therapy Period
NCT01020786 (9) [back to overview]Progression Free Survival (PFS) During the Maintenance Therapy Period
NCT01020786 (9) [back to overview]Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Maintenance Therapy Period
NCT01020786 (9) [back to overview]Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) During the Induction and Maintenance Therapy Periods
NCT01020786 (9) [back to overview]Percentage of Participants Who Achieve a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Induction and Maintenance Therapy Periods
NCT01020786 (9) [back to overview]Overall Survival (OS) During the Induction and Maintenance Therapy Periods
NCT01020786 (9) [back to overview]Progression Free Survival (PFS) During the Induction and Maintenance Therapy Periods
NCT01020786 (9) [back to overview]Percentage of Participants Who Observe a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Induction Therapy Period
NCT01020786 (9) [back to overview]Percentage of Participants Who Achieve a Complete Response (CR) or a Partial Response (PR) During the Induction Therapy Period
NCT01036087 (2) [back to overview]Number of Participants That Achieved Pathologic Complete Response (CR)
NCT01036087 (2) [back to overview]Number of Participants With Treatment-related Adverse Events (AEs)
NCT01041781 (7) [back to overview]Overall Survival
NCT01041781 (7) [back to overview]Progression-free Survival
NCT01041781 (7) [back to overview]Incidence of Toxicities as Assessed by NCI CTCAE v. 4.0
NCT01041781 (7) [back to overview]Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the First Quartile (Q1)
NCT01041781 (7) [back to overview]Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Median Quartile (Q2)
NCT01041781 (7) [back to overview]Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Third Quartile (Q3)
NCT01041781 (7) [back to overview]Response Rate
NCT01042288 (5) [back to overview]Median Overall Survival (OS)
NCT01042288 (5) [back to overview]Frequency of Adverse Events and Severity as a Measure of Toxicity
NCT01042288 (5) [back to overview]Median Time to Progression (TTP)
NCT01042288 (5) [back to overview]Median Progression-free Survival (PFS)
NCT01042288 (5) [back to overview]Objective Response Rate
NCT01042522 (3) [back to overview]Tumor Response Rate
NCT01042522 (3) [back to overview]Overall Survival (OS)
NCT01042522 (3) [back to overview]Progression-free Survival (PFS)
NCT01051570 (6) [back to overview]Overall Survival
NCT01051570 (6) [back to overview]Pharmacokinetics: Observed Carboplatin AUC Was Estimated Based on the Concentration in the 2.75-h Sample.
NCT01051570 (6) [back to overview]PSA Response Rate
NCT01051570 (6) [back to overview]Time to Progression (TTP)
NCT01051570 (6) [back to overview]Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria
NCT01051570 (6) [back to overview]Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6)
NCT01063075 (7) [back to overview]Total Carboplatin PK: Maximum Observed Plasma Concentration (Cmax)
NCT01063075 (7) [back to overview]Cetuximab PK: Confirmatory Serum Concentration
NCT01063075 (7) [back to overview]Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)
NCT01063075 (7) [back to overview]Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])
NCT01063075 (7) [back to overview]Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
NCT01063075 (7) [back to overview]Total Carboplatin PK: Time of Maximum Observed Plasma Concentration (Tmax)
NCT01063075 (7) [back to overview]Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss)
NCT01063283 (2) [back to overview]Response Rate
NCT01063283 (2) [back to overview]Change in 24 Hour Diastolic Blood Pressure (DBP)
NCT01064479 (5) [back to overview]Number of Participants With Tumor Response (Complete Response [CR] + Partial Response [PR])
NCT01064479 (5) [back to overview]Rash Rates
NCT01064479 (5) [back to overview]Progression Free Survival (PFS)
NCT01064479 (5) [back to overview]Overall Survival (OS)
NCT01064479 (5) [back to overview]Disease Control (CR + PR + Stable Disease [SD])
NCT01075100 (6) [back to overview]Overall Survival (OS)
NCT01075100 (6) [back to overview]Objective Response Rate (ORR)
NCT01075100 (6) [back to overview]Duration of Response
NCT01075100 (6) [back to overview]Clinical Benefit Rate (CBR)
NCT01075100 (6) [back to overview]Time to Response
NCT01075100 (6) [back to overview]Progression-free Survival (PFS)
NCT01076504 (5) [back to overview]Toxicity/Safety
NCT01076504 (5) [back to overview]Time to Progression
NCT01076504 (5) [back to overview]Objective Response Rate
NCT01076504 (5) [back to overview]Overall Survival
NCT01076504 (5) [back to overview]1-year Survival
NCT01081041 (10) [back to overview]Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013
NCT01081041 (10) [back to overview]Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing
NCT01081041 (10) [back to overview]Number of Participants With Anti-Cetuximab Antibodies
NCT01081041 (10) [back to overview]Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013
NCT01081041 (10) [back to overview]Cmax of Cetuximab at Steady State
NCT01081041 (10) [back to overview]Progression-Free Survival (PFS)
NCT01081041 (10) [back to overview]Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
NCT01081041 (10) [back to overview]Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR)
NCT01081041 (10) [back to overview]Overall Survival (OS)
NCT01081041 (10) [back to overview]Area Under the Concentration Curve (AUC) of Cetuximab at Steady State
NCT01081262 (10) [back to overview]Patient Reported Quality of Life
NCT01081262 (10) [back to overview]Patient Reported Neurotoxicity
NCT01081262 (10) [back to overview]Patient Reported Neurotoxicity
NCT01081262 (10) [back to overview]Patient Reported Quality of Life
NCT01081262 (10) [back to overview]Overall Survival
NCT01081262 (10) [back to overview]Progression-free Survival
NCT01081262 (10) [back to overview]Participants With Grade 1 or Higher Non-serious Adverse Effects Assessed by CTCAE Version 4.0
NCT01081262 (10) [back to overview]Patient Reported Neurotoxicity
NCT01081262 (10) [back to overview]Objective Tumor Response
NCT01081262 (10) [back to overview]Patient Reported Quality of Life
NCT01081951 (3) [back to overview]Overall Survival (OS)
NCT01081951 (3) [back to overview]Percentage Change in Tumour Size
NCT01081951 (3) [back to overview]Progression Free Survival (PFS)
NCT01087970 (6) [back to overview]Overall Survival (OS)
NCT01087970 (6) [back to overview]Percentage of Participants Having a Confirmed Partial Response (PR) or Complete Response (CR)
NCT01087970 (6) [back to overview]Number of Participants Who Died While on Treatment and Died During 30-Day Post-Treatment Discontinuation Follow-Up (FU)
NCT01087970 (6) [back to overview]Change From Baseline in Participant-Reported European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L)
NCT01087970 (6) [back to overview]Progression-Free Survival (PFS)
NCT01087970 (6) [back to overview]Change From Baseline in Performance Status Scale for Head and Neck Cancer (PSS-HNC)
NCT01088802 (5) [back to overview]Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: Xerostomia Questionnaire (XQ)
NCT01088802 (5) [back to overview]Percentage of Patients Free of Grade 3+ Late Toxicity
NCT01088802 (5) [back to overview]Percentage of Patients With Locoregional Tumor Control
NCT01088802 (5) [back to overview]Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: M.D. Anderson Dysphagia Inventory (MDADI)
NCT01088802 (5) [back to overview]Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: MD Anderson Symptom Inventory-head and Neck Cancer (MDASI-HN)
NCT01096368 (10) [back to overview]EFS of Children With Incompletely Resected Ependymoma Who Are Unable to Achieve a Complete Response (CR) by Post-operative Induction Chemotherapy or by Second Surgery and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy
NCT01096368 (10) [back to overview]EFS of Children With Supratentorial Classic Ependymoma Who Achieve Complete Resection at First or Second Surgery or Children Who Achieve Complete Response (CR) After Induction Chemo and Who Are Non-randomly Assigned to Observation
NCT01096368 (10) [back to overview]EFS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
NCT01096368 (10) [back to overview]Overall Survival (OS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
NCT01096368 (10) [back to overview]OS of Children With Supratentorial Classic Ependymoma Who Achieve Complete Resection at First or Second Surgery or Children Who Achieve Complete Response (CR) After Induction Chemo and Who Are Non-randomly Assigned to Observation
NCT01096368 (10) [back to overview]OS of Children With Incompletely Resected Ependymoma Who Are Unable to Achieve a Complete Response (CR) by Post-operative Induction Chemotherapy or by Second Surgery and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy
NCT01096368 (10) [back to overview]OS in Children With Incomplete Resection After Initial Surgery Who Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
NCT01096368 (10) [back to overview]OS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only.
NCT01096368 (10) [back to overview]Event-free Survival (EFS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
NCT01096368 (10) [back to overview]EFS With Incomplete Resection After Initial Surgery, Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only
NCT01097057 (4) [back to overview]Number of Participants Requiring One or Two Apheresis Collection Days to Reach ≥5 x 10^6 CD34 Cells/kg
NCT01097057 (4) [back to overview]Total Number of Participants Who Did Not Collect ≥5 x 10^6 CD34 Cells/kg in a Maximum of Four Apheresis Days
NCT01097057 (4) [back to overview]Number of Patients Who Achieved ≥5 x 10^6 CD34 Cells/kg in ≤4 Apheresis Days
NCT01097057 (4) [back to overview]Number of Patients to Mobilize ≥5 x 10^6 CD34 Cells/kg Autologous PBSC (Efficacy)
NCT01097746 (2) [back to overview]Progression-free Survival of Optimal (RO) 1 cm
NCT01097746 (2) [back to overview]Number of Participants With Treatment Success
NCT01100931 (3) [back to overview]Number of Participants With Adverse Events
NCT01100931 (3) [back to overview]Phase 2 Objective Response Rate (Partial Response (PR) + Complete Response (CR)).
NCT01100931 (3) [back to overview]Phase 1 Safe and Tolerable Phase 2 Dose.
NCT01107626 (3) [back to overview]Response Rate
NCT01107626 (3) [back to overview]Progression-free Survival
NCT01107626 (3) [back to overview]Overall Survival
NCT01127763 (4) [back to overview]Median Progression-free Survival Time
NCT01127763 (4) [back to overview]Toxicity Profile-Hematological
NCT01127763 (4) [back to overview]Toxicity Profile-Non Hematological
NCT01127763 (4) [back to overview]Clinical Benefit Rate (Complete Response, Partial Response, and Stable Disease That Lasts More Than 6 Months)
NCT01133756 (1) [back to overview]Number of Participants With Dose Limiting Toxicity (DLT)
NCT01144442 (2) [back to overview]Clinical Response
NCT01144442 (2) [back to overview]Feasibility of HIPC in Recurrent Disease Setting
NCT01146795 (4) [back to overview]Progression-free Survival (PFS)
NCT01146795 (4) [back to overview]Response Rate
NCT01146795 (4) [back to overview]Quality of Life (QOL) Score
NCT01146795 (4) [back to overview]Number of Protocol Defined Adverse Events in Patients Receiving Neoadjuvant Carboplatin, Paclitaxel, and Bevacizumab
NCT01151761 (8) [back to overview]Median Time to Overall Survival
NCT01151761 (8) [back to overview]Liver Transplant Rate
NCT01151761 (8) [back to overview]Freedom From Local Progression at 12 Months
NCT01151761 (8) [back to overview]Liver Transplant Conversion Rate
NCT01151761 (8) [back to overview]Serum CA 19-9 Levels
NCT01151761 (8) [back to overview]Progression-free Survival at 12 Months
NCT01151761 (8) [back to overview]Pathologic Complete Response Rate
NCT01151761 (8) [back to overview]Overall Survival at 12 Months
NCT01160744 (7) [back to overview]Change in Tumor Size (CTS)
NCT01160744 (7) [back to overview]Overall Survival (OS)
NCT01160744 (7) [back to overview]Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]
NCT01160744 (7) [back to overview]Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)]
NCT01160744 (7) [back to overview]Progression-Free Survival (PFS)
NCT01160744 (7) [back to overview]Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died
NCT01160744 (7) [back to overview]Duration of Response (DOR)
NCT01165112 (4) [back to overview]Maximally Tolerated Dose of Bendamustine Hydrochloride That Can be Combined With Rituximab, Carboplatin, and Etoposide Chemotherapy in Patients With Relapsed or Refractory Lymphoid Malignancies
NCT01165112 (4) [back to overview]Safety and Toxicity of This Regimen
NCT01165112 (4) [back to overview]Preliminary Assessment of the Efficacy of This Regimen
NCT01165112 (4) [back to overview]Ability to Proceed to Peripheral Blood Stem Cell (PBSC) Collection Following Treatment (Impact of This Regimen on Stem Cell Reserve)
NCT01165216 (8) [back to overview]Trough Observed Serum Concentration (Cmin) of Ipilimumab
NCT01165216 (8) [back to overview]Number of Participants With Death As Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), AEs Leading to Discontinuation, Drug-related AEs Leading to Discontinuation
NCT01165216 (8) [back to overview]Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease
NCT01165216 (8) [back to overview]Time of Maximum Observed Serum Concentration (Tmax)
NCT01165216 (8) [back to overview]Serum Half-life (T-HALF) of Ipilimumab
NCT01165216 (8) [back to overview]Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
NCT01165216 (8) [back to overview]Maximum Serum Concentration (Cmax) of Ipilimumab
NCT01165216 (8) [back to overview]Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab
NCT01167192 (5) [back to overview]Time to Disease Progression
NCT01167192 (5) [back to overview]Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events
NCT01167192 (5) [back to overview]Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR)
NCT01167192 (5) [back to overview]Number of Participants With Surgical Complications
NCT01167192 (5) [back to overview]Overall Survival Rate
NCT01167712 (3) [back to overview]Median Duration of First Quartile Survival
NCT01167712 (3) [back to overview]Quality of Life Score as Measured by Functional Assessment of Cancer Therapy-Ovary-Total Outcome Index (Fact-O TOI)
NCT01167712 (3) [back to overview]Progression-Free Survival
NCT01169636 (3) [back to overview]Maximum Tolerated Dose (MTD) of Panobinostat + ICE
NCT01169636 (3) [back to overview]Percentage of Participants With Failure Free Survival (FFS)
NCT01169636 (3) [back to overview]Number of Participants With Complete Remission (CR)
NCT01174238 (5) [back to overview]Optimal Interval Between the End of Axitinib Therapy and Initiation of Chemotherapy
NCT01174238 (5) [back to overview]Overall Survival (OS)
NCT01174238 (5) [back to overview]Objective Response Rate (ORR)
NCT01174238 (5) [back to overview]Increase From Nadir in the Sum of Maximum (18)F-FLT Uptake Values After Treatment Holiday
NCT01174238 (5) [back to overview]Time to Progression (TTP)
NCT01183559 (2) [back to overview]The Number of Participants With Adverse Events
NCT01183559 (2) [back to overview]Maximum Tolerated Dose of Vandetanib
NCT01188876 (6) [back to overview]Maximum Tolerated Dose (MTD)
NCT01188876 (6) [back to overview]Maximum Concentration of Drug in Plasma (Cmax)
NCT01188876 (6) [back to overview]Area Under the Plasma Drug Concentration-Time Curve (AUC)
NCT01188876 (6) [back to overview]Progression Free Survival
NCT01188876 (6) [back to overview]Treatment Related Adverse Events
NCT01188876 (6) [back to overview]Overall Survival
NCT01196390 (6) [back to overview]Disease-free Survival (DFS)
NCT01196390 (6) [back to overview]Number of Participants With Any Cardiac Adverse Events Regardless of Attribution
NCT01196390 (6) [back to overview]Overall Survival
NCT01196390 (6) [back to overview]Percentage of Participants With Pathologic Complete Response at Surgery
NCT01196390 (6) [back to overview]Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment
NCT01196390 (6) [back to overview]Frequency of Highest Grade Adverse Event Per Participant
NCT01196429 (5) [back to overview]Frequency and Severity of Toxicity
NCT01196429 (5) [back to overview]Proportion of Patients Who Are Alive and Progression-free for at Least 12 Months After Study Entry in Patients With Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer in the Following Populations: Patients in the U.S./Worldwide and Japan
NCT01196429 (5) [back to overview]Progression-free Survival
NCT01196429 (5) [back to overview]Overall Survival
NCT01196429 (5) [back to overview]Objective Tumor Response
NCT01199055 (6) [back to overview]Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)
NCT01199055 (6) [back to overview]Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01199055 (6) [back to overview]CS-7017-Related Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group After Administration of CS-7017 and Carboplatin/Paclitaxel in Chemotherapy-naïve Participants With Stage IIIb/IV Non-small Cell Lung Cancer
NCT01200342 (2) [back to overview]Number of Participants With Response
NCT01200342 (2) [back to overview]Overall Response Rate (Percentage Subjects With Confirmed Complete or Partial Response)
NCT01201265 (9) [back to overview]Progression-free Survival (PFS)
NCT01201265 (9) [back to overview]Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)
NCT01201265 (9) [back to overview]Percentage of Participants Achieving a Clinical Benefit Response (CBR)
NCT01201265 (9) [back to overview]Change From Baseline in Systolic Blood Pressure (SBP)
NCT01201265 (9) [back to overview]Change From Baseline in Diastolic Blood Pressure (DBP)
NCT01201265 (9) [back to overview]Time to Progression (TTP)
NCT01201265 (9) [back to overview]Number of Participants With an Adverse Event (AE)
NCT01201265 (9) [back to overview]Overall Survival (OS)
NCT01201265 (9) [back to overview]Percentage of Participants Achieving an Overall Response
NCT01218048 (9) [back to overview]Progression-free Survival (PFS)
NCT01218048 (9) [back to overview]Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)
NCT01218048 (9) [back to overview]T Cell Activation
NCT01218048 (9) [back to overview]Change in Tumor Size
NCT01218048 (9) [back to overview]Serum Cytokines Levels
NCT01218048 (9) [back to overview]Overall Survival (OS)
NCT01218048 (9) [back to overview]Objective Response (Rate)
NCT01218048 (9) [back to overview]3-year Progression-free Survival (PFS)
NCT01218048 (9) [back to overview]NK Cell Activation
NCT01218516 (5) [back to overview]Duration of Response (DR)
NCT01218516 (5) [back to overview]Overall Survival (OS)
NCT01218516 (5) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)
NCT01218516 (5) [back to overview]Overall Response Rate (ORR)
NCT01218516 (5) [back to overview]Progression-free Survival (PFS)
NCT01219777 (2) [back to overview]Tolerated Dose
NCT01219777 (2) [back to overview]Toxicity and Response Rates Based on Imaging and Surgical Outcomes
NCT01220128 (28) [back to overview]Number of Subjects With Alanine Aminotransferase Increased Abnormality, by Common Terminology Criteria for Adverse Events (CTCAE) Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Lymphocyte Count Decreased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Hyponatremia Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Hypocalcemia Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Hypokalemia Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Hypoalbuminemia Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Hypernatremia Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Hyperkalemia Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Hypercalcemia Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Severe Toxicities
NCT01220128 (28) [back to overview]Number of Subjects With Hemoglobin Increased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Serious Adverse Events (SAEs), Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported
NCT01220128 (28) [back to overview]Number of Subjects With Aspartate Aminotransferase Increased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With White Blood Cell Decreased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Patients With an Anti-Wilm's Tumor Gene (Anti-WT1) Humoral Response
NCT01220128 (28) [back to overview]Number of Subjects With Anemia, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Serious Adverse Events (SAEs), by CTCAE Maximum Grade Reported
NCT01220128 (28) [back to overview]Number of Subjects With Creatine Increased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Breast Cancer Pathological Response
NCT01220128 (28) [back to overview]Number of Subjects With Serious Adverse Events SAE(s)
NCT01220128 (28) [back to overview]Number of Subjects With Platelet Count Decreased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Neutrophil Count Decreased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Patients With Adverse Events (AEs), by CTCAE Maximum Grade Reported
NCT01220128 (28) [back to overview]Number of Subjects With Adverse Events (AEs) Assessed by the Investigators as Causally Related to GSK2302024A Treatment, by CTCAE Maximum Grade Reported
NCT01220128 (28) [back to overview]Number of Subjects With Lymphocyte Count Increased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Blood Bilirubin Increased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Subjects With Alkaline Phosphatase Increased Abnormality, by CTCAE Maximum Grade
NCT01220128 (28) [back to overview]Number of Patients With Adverse Events (AEs)
NCT01221753 (1) [back to overview]4-y Overall Survival Rate
NCT01237678 (7) [back to overview]Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT01237678 (7) [back to overview]Occurrence of Dose Limiting Toxicities (DLT)
NCT01237678 (7) [back to overview]Progression Free Survival (PFS) Rate at 6 Months
NCT01237678 (7) [back to overview]Progression Free Survival (PFS) in Phase II
NCT01237678 (7) [back to overview]Overall Survival (OS) Rate at 12 Months
NCT01237678 (7) [back to overview]Median Overall Survival (OS) in Phase II
NCT01237678 (7) [back to overview]Maximum Tolerated Dose (MTD) of IMGN901
NCT01239732 (7) [back to overview]Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0
NCT01239732 (7) [back to overview]Percentage of Participants Achieving an Overall Response by 50% Carcinoma Antigen 125 (CA-125) Response Criteria
NCT01239732 (7) [back to overview]Overall Survival (OS)
NCT01239732 (7) [back to overview]Duration of Objective Response (DOR)
NCT01239732 (7) [back to overview]Progression-Free Survival (PFS)
NCT01239732 (7) [back to overview]Percentage of Participants With at Least One Adverse Event (AE)
NCT01239732 (7) [back to overview]Percentage of Participants Achieving an Overall Response by RECIST Version 1.0 and/or 50% CA-125 Response Criteria
NCT01248949 (21) [back to overview]Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline
NCT01248949 (21) [back to overview]Number of Participants With Dose Limiting Toxicities (DLTs)
NCT01248949 (21) [back to overview]Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs)
NCT01248949 (21) [back to overview]Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs)
NCT01248949 (21) [back to overview]Number of Participants With Positive Anti-Drug Antibody (ADA)
NCT01248949 (21) [back to overview]Time to Progression (TTP)
NCT01248949 (21) [back to overview]Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs)
NCT01248949 (21) [back to overview]Systemic Clearance (CL) of MEDI3617
NCT01248949 (21) [back to overview]Overall Survival (OS)
NCT01248949 (21) [back to overview]Progression-Free Survival (PFS)
NCT01248949 (21) [back to overview]Duration of Response (DOR)
NCT01248949 (21) [back to overview]Time to Response (TTR)
NCT01248949 (21) [back to overview]Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617
NCT01248949 (21) [back to overview]Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617
NCT01248949 (21) [back to overview]Circulating Levels of Angiopoietin 2 (Ang2)
NCT01248949 (21) [back to overview]Maximum Observed Serum Concentration (Cmax) of MEDI3617
NCT01248949 (21) [back to overview]Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs)
NCT01248949 (21) [back to overview]Objective Response Rate (ORR)
NCT01248949 (21) [back to overview]Terminal Elimination Half Life (t1/2) of MEDI3617
NCT01248949 (21) [back to overview]Maximum Tolerated Dose (MTD)
NCT01248949 (21) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
NCT01248962 (1) [back to overview]The Odds Ratio for the Relationship of Baseline Variables to the Carboplatin Hypersensitivity Rate
NCT01263782 (2) [back to overview]Overall Response Rate
NCT01263782 (2) [back to overview]Progression Free Survival
NCT01268059 (20) [back to overview]Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose
NCT01268059 (20) [back to overview]Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575
NCT01268059 (20) [back to overview]Time to Progression (TTP)
NCT01268059 (20) [back to overview]Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575
NCT01268059 (20) [back to overview]Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose
NCT01268059 (20) [back to overview]Percentage of Participants With Positive Anti-MEDI-575 Antibodies
NCT01268059 (20) [back to overview]Progression Free-Survival (PFS)
NCT01268059 (20) [back to overview]Overall Survival (OS)
NCT01268059 (20) [back to overview]Objective Response Rate (ORR)
NCT01268059 (20) [back to overview]Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b
NCT01268059 (20) [back to overview]Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575
NCT01268059 (20) [back to overview]Time to Response (TTR)
NCT01268059 (20) [back to overview]Duration of Response (DR)
NCT01268059 (20) [back to overview]Best Overall Response
NCT01268059 (20) [back to overview]Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs
NCT01268059 (20) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT01268059 (20) [back to overview]Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose
NCT01268059 (20) [back to overview]Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples
NCT01268059 (20) [back to overview]Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples
NCT01268059 (20) [back to overview]Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs
NCT01275664 (2) [back to overview]Number of Participants With Complete Control Defined as no Vomiting and no Use of Rescue Medications (for Nausea or Emesis)
NCT01275664 (2) [back to overview]Frequency of Adverse Effects as Assessed by the NCI CTCAE v 4.0
NCT01280058 (5) [back to overview]Overall Survival
NCT01280058 (5) [back to overview]Overall Response Rate (Partial or Complete Response) Evaluated Using the Standard RECIST v. 1.1
NCT01280058 (5) [back to overview]Progression-free Survival Using RECIST v. 1.1
NCT01280058 (5) [back to overview]Percentage of Patients With Ras Pathway Activation
NCT01280058 (5) [back to overview]Incidence of Severe (Grade 3+) Adverse Events That Are Classified as Either Possibly, Probably, or Definitely Related to Study Treatment, as Assessed by NCI CTCAE Version 4.0
NCT01283334 (2) [back to overview]To Measure the Safety and Clinical Effectiveness of the Combination of Carboplatin, Cetuximab and RAD001 in Patients With Advanced (Recurrent or Metastatic) Head and Neck Cancer
NCT01283334 (2) [back to overview]Progression-free Survival (PFS)
NCT01285609 (3) [back to overview]Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy at Primary Endpoint
NCT01285609 (3) [back to overview]Median Number of Months With Progression Free Survival (PFS) Per mWHO in Participants Who Have Received at Least One Dose of Blinded Study Therapy at Primary Endpoint
NCT01285609 (3) [back to overview]Overall Survival (OS) in All Randomized Participants at Primary Endpoint
NCT01287520 (10) [back to overview]Number of Participants With Best Overall Tumor Response
NCT01287520 (10) [back to overview]Recommended LY2090314 Dose for Phase 2 Studies (Maximum Tolerated Dose [MTD])
NCT01287520 (10) [back to overview]PK Parameter: Maximum Plasma Concentration (Cmax) of Pemetrexed (Pem)
NCT01287520 (10) [back to overview]PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)
NCT01287520 (10) [back to overview]PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314
NCT01287520 (10) [back to overview]PK Parameter: Cmax of Free Carboplatin
NCT01287520 (10) [back to overview]PK Parameter: AUC0-∞ of Free Carboplatin (Carb)
NCT01287520 (10) [back to overview]PK Parameter: AUC0-∞ of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)
NCT01287520 (10) [back to overview]Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of Pemetrexed (Pem)
NCT01287520 (10) [back to overview]Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of LY2090314
NCT01289353 (3) [back to overview]Number of Patients Who Experience Grade 2 or Higher Late Toxicities at or More Than 6 Months After Completion of Radiation Treatment (RT)
NCT01289353 (3) [back to overview]Number of Patients Who Experience Acute Toxicities at or More Than 6 Months After Completion of Radiation Treatment (RT)
NCT01289353 (3) [back to overview]Number of Patients Who Developed Grade 2-3 Acute Radiation Dermatitis Within 60 Days Post-RT
NCT01295944 (8) [back to overview]Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)
NCT01295944 (8) [back to overview]Overall Survival (OS)
NCT01295944 (8) [back to overview]Percentage of Participants That Have Progressive Free Survival (PFS) After 1 Year
NCT01295944 (8) [back to overview]Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Spine Tumors (MDASI-SP) Instrument
NCT01295944 (8) [back to overview]Mean Symptom Interference With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT)
NCT01295944 (8) [back to overview]Mean Symptom Interference With Daily Activities Using the MD Anderson Symptom Inventory for Spine Tumors (MDASI-SP) Instrument
NCT01295944 (8) [back to overview]Number of Participants With a (Complete Response (CR) + Partial Response (PR))
NCT01295944 (8) [back to overview]Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT)
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Nintedanib
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carboplatin (Determined as Total Platinum)
NCT01314105 (16) [back to overview]Maximum Tolerated Dose of Nintedanib Based on the Occurrence of DLTs During Treatment Course 1
NCT01314105 (16) [back to overview]Dose Limiting Toxicities During Treatment Course 1
NCT01314105 (16) [back to overview]Maximum Measured Plasma Concentration (Cmax) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2
NCT01314105 (16) [back to overview]Maximum Measured Plasma Concentration (Cmax) of Nintedanib
NCT01314105 (16) [back to overview]Maximum Measured Plasma Concentration (Cmax) of Carboplatin During Course 1 and Course 2 (Determined as Ultrafilterable Platinum)
NCT01314105 (16) [back to overview]Maximum Measured Plasma Concentration (Cmax) of Carboplatin (Total Platinum)
NCT01314105 (16) [back to overview]Incidence and Intensity of Adverse Events
NCT01314105 (16) [back to overview]Change From Baseline in Safety Laboratory Parameters
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC 0-inf) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC 0-inf) of Carboplatin During Treatment Course 1 and Course 2 (Determined as Ultrafilterable Platinum)
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Nintedanib
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Carboplatin (Determined as Ultrafilterable Platinum)
NCT01314105 (16) [back to overview]Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Carboplatin (Determined as Total Platinum)
NCT01317615 (6) [back to overview]Percentage of Participants With Overall Response Rate (ORR)
NCT01317615 (6) [back to overview]Percentage of Participants With Disease Control Rate (DCR)
NCT01317615 (6) [back to overview]Progression Free Survival (PFS)
NCT01317615 (6) [back to overview]Percentage of Participants Progression-free
NCT01317615 (6) [back to overview]Percentage of Participants Progression-free
NCT01317615 (6) [back to overview]Overall Survival (OS)
NCT01333033 (5) [back to overview]pCR Compared Among Non-responders Between Induction Treatment Arms if Treatment Regimens Are Found to be Efficacious
NCT01333033 (5) [back to overview]pCR Compared Between Induction Treatment Arms Among PET/CT Responders
NCT01333033 (5) [back to overview]PET/CT Response Between Treatment Arms
NCT01333033 (5) [back to overview]Progression Free Survival (PFS) Among PET/CT Non-responders Within Each Induction Treatment Group
NCT01333033 (5) [back to overview]Complete Pathological Response (pCR) of PET/CT Non-responders
NCT01344824 (3) [back to overview]Progression-free Survival
NCT01344824 (3) [back to overview]Subjects Experiencing Toxicity
NCT01344824 (3) [back to overview]Overall Survival
NCT01357161 (8) [back to overview]Part 2: Median Progression-free Survival (PFS) in Weeks Based on Enhanced Response Evaluation Criteria In Solid Tumors Version 1.1 (Enhanced RECIST 1.1) by Independent Radiology Review
NCT01357161 (8) [back to overview]Part 1: Objective Response Rate (ORR) Per Gynecological Cancer Intergroup (GCIG) Criteria Based on Both RECIST 1.1 and Cancer Antigen 125 (CA-125) Level by Independent Radiology Review
NCT01357161 (8) [back to overview]Part 1: Number of Participants With a Dose Limiting Toxicity (DLT)
NCT01357161 (8) [back to overview]Parts 1 and 2: Percentage of Participants That Experienced an Adverse Event (AE)
NCT01357161 (8) [back to overview]Parts 1 and 2: Percentage of Participants That Discontinued Study Treatment Due to an AE
NCT01357161 (8) [back to overview]Part 2: Median PFS in Weeks Based on RECIST 1.1 by Independent Radiology Review
NCT01357161 (8) [back to overview]Part 2: Median Overall Survival (OS) in Months
NCT01357161 (8) [back to overview]Part 2: ORR Per GCIG Criteria Based on Both Enhanced RECIST 1.1 and CA125 Level by Independent Radiology Review
NCT01358877 (30) [back to overview]Percentage of Participants With Primary Cardiac Event
NCT01358877 (30) [back to overview]Peak Serum Concentration (Cmax) of Pertuzumab
NCT01358877 (30) [back to overview]Cmin of Trastuzumab
NCT01358877 (30) [back to overview]Cmax of Trastuzumab
NCT01358877 (30) [back to overview]Change From Baseline in LVEF to Worst Post-Baseline Value
NCT01358877 (30) [back to overview]Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score
NCT01358877 (30) [back to overview]Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score
NCT01358877 (30) [back to overview]Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores
NCT01358877 (30) [back to overview]Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3
NCT01358877 (30) [back to overview]Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores
NCT01358877 (30) [back to overview]Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores
NCT01358877 (30) [back to overview]Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score
NCT01358877 (30) [back to overview]Percentage of Participants With Secondary Cardiac Event
NCT01358877 (30) [back to overview]Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Percentage of Participants Who Died
NCT01358877 (30) [back to overview]Trough Serum Concentration (Cmin) of Pertuzumab
NCT01358877 (30) [back to overview]Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings
NCT01358877 (30) [back to overview]Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain
NCT01358877 (30) [back to overview]Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain
NCT01358877 (30) [back to overview]Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain
NCT01358877 (30) [back to overview]Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain
NCT01358877 (30) [back to overview]Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain
NCT01362127 (3) [back to overview]Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia.
NCT01362127 (3) [back to overview]Safety of Respective Neoadjuvant Therapies.
NCT01362127 (3) [back to overview]HRQOL and Swallowing Function
NCT01367002 (3) [back to overview]To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0
NCT01367002 (3) [back to overview]Progression Free Survival Differences Between Treatment Arms.
NCT01367002 (3) [back to overview]To Assess Overall Survival (OS)
NCT01376310 (1) [back to overview]Number of Participants With Adverse Events
NCT01386385 (5) [back to overview]Incidence of Serious (>= Grade 3) Adverse Events as Measured by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase II)
NCT01386385 (5) [back to overview]Progression-free Survival of Patients Treated With Chemoradiotherapy Plus Veliparib (Phase II)
NCT01386385 (5) [back to overview]Overall Survival (Phase II)
NCT01386385 (5) [back to overview]Objective Response Rate (Phase II)
NCT01386385 (5) [back to overview]Maximum Tolerated Dose of Veliparib When Given Concurrently With Standard Carboplatin/Paclitaxel and Radiotherapy, Determined According to Incidence of Dose Limiting Toxicity (DLT) (Phase I)
NCT01388647 (4) [back to overview]Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb
NCT01388647 (4) [back to overview]Clinical Response
NCT01388647 (4) [back to overview]Dose Limiting Toxicity (DLT)
NCT01388647 (4) [back to overview]Pathologic Response
NCT01395537 (3) [back to overview]PHASE I: Number of Patients That Experience a Grade 3-4 Dose Limiting Toxicity
NCT01395537 (3) [back to overview]To Determine the Overall Survival
NCT01395537 (3) [back to overview]PHASE II: To Assess the Response Rate to This Regimen.
NCT01404260 (1) [back to overview]Progression Free Survival
NCT01412229 (8) [back to overview]Patient-reported Quality of Life Scores
NCT01412229 (8) [back to overview]Number of Participants With at Least One Grade 3-4 Toxicity
NCT01412229 (8) [back to overview]Number of Participants With at Least One Grade 3-4 Toxicity, Listed by Event
NCT01412229 (8) [back to overview]Rate of Complete Response Following Induction Chemotherapy
NCT01412229 (8) [back to overview]Progression Free Survival
NCT01412229 (8) [back to overview]Overall Survival
NCT01412229 (8) [back to overview]Objective Response Rate (CR+PR)
NCT01412229 (8) [back to overview]Complete Response Rate (CR)
NCT01413750 (3) [back to overview]Progression-free Survival (PFS)
NCT01413750 (3) [back to overview]Maximum Tolerated Dose (MTD) (Phase I)
NCT01413750 (3) [back to overview]Dose Limiting Toxicity (DLT) (Phase I)
NCT01414608 (6) [back to overview]Patterns of Disease Recurrence
NCT01414608 (6) [back to overview]Radiation Protocol Compliance
NCT01414608 (6) [back to overview]Quality of Life for Global Health Status
NCT01414608 (6) [back to overview]Progression-free Survival Rate at 5 Years
NCT01414608 (6) [back to overview]Overall Survival Rate at 5 Years
NCT01414608 (6) [back to overview]Number of Participants With Adverse Events (Grade 3 or Higher) in First Year
NCT01437449 (4) [back to overview]Overall Survival (OS)
NCT01437449 (4) [back to overview]Grade 3, 4, and 5 Related Adverse Events (Toxicities)
NCT01437449 (4) [back to overview]Progression-free Survival (PFS)
NCT01437449 (4) [back to overview]Overall Response Rate (ORR)
NCT01439568 (4) [back to overview]Duration of Overall Response (DOR)
NCT01439568 (4) [back to overview]Progression Free Survival (PFS)
NCT01439568 (4) [back to overview]Overall Survival (OS)
NCT01439568 (4) [back to overview]Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])
NCT01443078 (2) [back to overview]Pathologic Response Rate
NCT01443078 (2) [back to overview]PERCIST Partial Metabolic Response
NCT01447225 (11) [back to overview]Pharmacokinetics (AUClast)
NCT01447225 (11) [back to overview]Pharmacokinetics
NCT01447225 (11) [back to overview]To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies
NCT01447225 (11) [back to overview]To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses
NCT01447225 (11) [back to overview]Immunogenicity
NCT01447225 (11) [back to overview]Objective Response Rate
NCT01447225 (11) [back to overview]To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies
NCT01447225 (11) [back to overview]To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed
NCT01447225 (11) [back to overview]To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel
NCT01447225 (11) [back to overview]To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin
NCT01447225 (11) [back to overview]To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine
NCT01450761 (3) [back to overview]Progression Free Survival (PFS) Time in Participants Who Have Received at Least One Dose of Blinded Study Therapy
NCT01450761 (3) [back to overview]Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy
NCT01450761 (3) [back to overview]Overall Survival in All Randomized Participants
NCT01454102 (6) [back to overview]Number of Participants With Abnormalities in Selected Thyroid Clinical Laboratory Tests
NCT01454102 (6) [back to overview]Progression-Free Survival Rate (PFSR) at Week 24
NCT01454102 (6) [back to overview]Number of Participants With Abnormalities in Selected Hepatic Clinical Laboratory Tests
NCT01454102 (6) [back to overview]Objective Response Rate (ORR)
NCT01454102 (6) [back to overview]Number of Participants Who Experienced Selected Adverse Events
NCT01454102 (6) [back to overview]Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death
NCT01458366 (8) [back to overview]Phase I: Overall Frequency of Response
NCT01458366 (8) [back to overview]Total Overall Survival for Transplant vs Non-transplant
NCT01458366 (8) [back to overview]Phase I: Maximum-Tolerated Dose of Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide (BOCE)
NCT01458366 (8) [back to overview]Overall Progression-Free Survival
NCT01458366 (8) [back to overview]Overall Frequency of Response With Combination of Bendamustine, Ofatumumab, Carboplatin, and Etoposide at Maximum Tolerated Dose (MTD)
NCT01458366 (8) [back to overview]Overall Complete Response (CR) and Partial Response (PR) Rate
NCT01458366 (8) [back to overview]Overall Proportion of Patients Who Are Able to Undergo Stem Cell Transplant (SCT)
NCT01458366 (8) [back to overview]Overall Safety and Tolerability of the Combination of Bendamustine, Ofatumumab, Carboplatin, and Etoposide
NCT01505868 (8) [back to overview]Progression Free Survival (PFS) of Cabazitaxel-carboplatin Versus Cabazitaxel in the Phase II Portion of Study
NCT01505868 (8) [back to overview]Prostate Specific Antigen (PSA) Response Rate
NCT01505868 (8) [back to overview]Overall Survival (OS)
NCT01505868 (8) [back to overview]Aggressive Variant Prostate Carcinoma-Metastatic (ACPC-MS) Phenotypes Correlated to Response
NCT01505868 (8) [back to overview]Phase II Most Common Grade 3-5 Adverse Events
NCT01505868 (8) [back to overview]Bone-Specific Alkaline Phosphatase Response
NCT01505868 (8) [back to overview]Maximum Tolerated Dosage (MTD) of Cabazitaxel-carboplatin in the Phase I Portion of Study
NCT01505868 (8) [back to overview]Urine N-Telopeptides Response
NCT01506609 (5) [back to overview]Overall Survival (OS)
NCT01506609 (5) [back to overview]Progression-Free Survival (PFS)
NCT01506609 (5) [back to overview]Clinical Benefit Rate (CBR) at Week 18
NCT01506609 (5) [back to overview]Change From Baseline at Week 18 in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Subscale Score
NCT01506609 (5) [back to overview]Objective Response Rate (ORR)
NCT01525966 (2) [back to overview]Overall Survival
NCT01525966 (2) [back to overview]Progression-free Survival
NCT01542736 (5) [back to overview]Overall Survival
NCT01542736 (5) [back to overview]Event-free Survival
NCT01542736 (5) [back to overview]Intellectual Competence Measured by IQ Score: Month 24
NCT01542736 (5) [back to overview]Intellectual Competence Measured by IQ Score: Month 60
NCT01542736 (5) [back to overview]Intellectual Competence Measured by IQ Score: Week 8
NCT01578551 (3) [back to overview]Response to Therapy
NCT01578551 (3) [back to overview]Overall Survial
NCT01578551 (3) [back to overview]Progression Free Survival (PFS)
NCT01602666 (6) [back to overview]3-year PFS Rate of Patients With Localized CNS Germinoma Who Were Treated With Reduced Dose Radiation Therapy
NCT01602666 (6) [back to overview]3-year Progression-free Survival (PFS) Rate of Patients With Nongerminomatous Germ Cell Tumor (NGGCT) Who Were Treated With Reduced Dose Whole Ventricular-field Irradiation
NCT01602666 (6) [back to overview]Estimation of the OS Distribution of Patients With Localized Germinoma Patients and CSF Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL
NCT01602666 (6) [back to overview]Estimation of the Overall Survival (OS) Distribution of Patients With NGGCT Treated With IFR Assessed
NCT01602666 (6) [back to overview]Estimation of the PFS Distribution of Patients With NGGCT Treated With Involved-field Radiation Therapy (IFR)
NCT01602666 (6) [back to overview]Estimation of the PFS Distribution of Patients With Localized Germinoma Patients and Cerebrospinal Fluid (CSF) Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL
NCT01612351 (9) [back to overview]Response Rates at the Primary Site
NCT01612351 (9) [back to overview]Voice and Swallowing Function- MD Anderson Dysphagia Inventory (MDADI)
NCT01612351 (9) [back to overview]Number of Patients Who Decreased in Risk Level Post Induction Chemotherapy.
NCT01612351 (9) [back to overview]Voice and Swallowing Function - Voice-Related Quality of Life Assessment (VRQOL)
NCT01612351 (9) [back to overview]Estimate the Pathologic Complete Response Rate at the Primary Site and in the Neck Following Induction Chemotherapy
NCT01612351 (9) [back to overview]Overall Response Rate
NCT01612351 (9) [back to overview]Feasibility of 3 Part Therapy
NCT01612351 (9) [back to overview]Number of Subjects Who Experience Grade 3/4 Adverse Events According to CTCAE 4.0
NCT01612351 (9) [back to overview]Response Rates at the Neck.
NCT01633541 (7) [back to overview]Functional Assessment QOL
NCT01633541 (7) [back to overview]Head and Neck Related Quality of Life (QOL)
NCT01633541 (7) [back to overview]Voice Related QOL
NCT01633541 (7) [back to overview]Percentage of Patients Experiencing Grade 3 or Higher Adverse Events.
NCT01633541 (7) [back to overview]Overall Response Rate (ORR)
NCT01633541 (7) [back to overview]Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment
NCT01633541 (7) [back to overview]Progression-free Survival
NCT01639001 (21) [back to overview]Objective Response Rate (ORR) - Percentage of Participants With Objective Response Based on IRR
NCT01639001 (21) [back to overview]Change From Baseline in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
NCT01639001 (21) [back to overview]Agreement Between Central Laboratory ALK FISH and ALK IHC Test Results - Molecular Profiling Evaluable
NCT01639001 (21) [back to overview]Time to Progression (TTP) Based on IRR
NCT01639001 (21) [back to overview]Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, or Cough Assessed Using Quality of Life Questionnaire Supplement Module for Lung Cancer (QLQ-LC13)
NCT01639001 (21) [back to overview]Progression-Free Survival (PFS) Based on IRR by Treatment Arm
NCT01639001 (21) [back to overview]Percentage of Participants With Disease Control at 12 Weeks Based on IRR
NCT01639001 (21) [back to overview]Overall Survival (OS)
NCT01639001 (21) [back to overview]Time to Tumor Response (TTR) Based on IRR
NCT01639001 (21) [back to overview]Intracranial Time to Progression (IC-TTP) Based on IRR
NCT01639001 (21) [back to overview]Extracranial Time to Progression (EC-TTP) Based on IRR
NCT01639001 (21) [back to overview]Duration of Response (DR) Based on IRR
NCT01639001 (21) [back to overview]Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)-Visual Analog Scale (VAS)
NCT01639001 (21) [back to overview]Change From Baseline in General Health Status as Assessed by EQ-5D-Index
NCT01639001 (21) [back to overview]Percentage of Participants With Visual Disturbance as Assessed by Visual Symptom Assessment Questionnaire (VSAQ-ALK)
NCT01639001 (21) [back to overview]Percentage of Participants With Visual Disturbance as Assessed by Visual Symptom Assessment Questionnaire (VSAQ-ALK)
NCT01639001 (21) [back to overview]Percentage of Participants With Treatment-Emergent AEs (Treatment Related)
NCT01639001 (21) [back to overview]Percentage of Participants With Treatment-Emergent Adverse Events (AEs; All Causalities)
NCT01639001 (21) [back to overview]Estimate of the Percentage of Participants Surviving at 1 Year and at 18 Months
NCT01639001 (21) [back to overview]Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30
NCT01639001 (21) [back to overview]Change From Baseline in Lung Cancer Symptom Scores as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)
NCT01649947 (2) [back to overview]Progression Free Survival (PFS)
NCT01649947 (2) [back to overview]Antitumor Activity, as Measured by Tumor Response Rate of Hydroxychloroquine, Paclitaxel, Carboplatin, and Bevacizumab (for Eligible Patients) in Patients With Advanced or Recurrent NSCLC Cancer
NCT01653912 (10) [back to overview]Phase 2 Safety: Number of Subjects Reporting Adverse Events
NCT01653912 (10) [back to overview]Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity
NCT01653912 (10) [back to overview]Phase 1 Safety: Number of Subjects Reporting Adverse Events
NCT01653912 (10) [back to overview]Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)
NCT01653912 (10) [back to overview]ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer
NCT01653912 (10) [back to overview]Progression Free Survival (PFS) by RECIST or Clinical Symptomatic Progression of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)
NCT01653912 (10) [back to overview]Phase 1: Maximum Tolerated Dose (MTD) of GSK2110183
NCT01653912 (10) [back to overview]PFS by RECIST of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)
NCT01653912 (10) [back to overview]Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125
NCT01653912 (10) [back to overview]Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity
NCT01663857 (7) [back to overview]Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score
NCT01663857 (7) [back to overview]Phase 1b: Recommended Phase 2 Dose of LY2228820 in Combination With Gemcitabine and Carboplatin (Maximum Tolerated Dose [MTD])
NCT01663857 (7) [back to overview]Phase 2: Overall Survival
NCT01663857 (7) [back to overview]Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820
NCT01663857 (7) [back to overview]Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820
NCT01663857 (7) [back to overview]Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin
NCT01663857 (7) [back to overview]Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)
NCT01696032 (11) [back to overview]Clinical Benefit Rate
NCT01696032 (11) [back to overview]Overall Survival
NCT01696032 (11) [back to overview]Progression Free Survival at 6 Months
NCT01696032 (11) [back to overview]Stage 1: Dose Limiting Toxicities
NCT01696032 (11) [back to overview]Stage 2: Progression Free Survival
NCT01696032 (11) [back to overview]Stage 1: Pharmacokinetic Parameter AUC0-8
NCT01696032 (11) [back to overview]Stage 1: Pharmacokinetic Parameter Cmax
NCT01696032 (11) [back to overview]Stage 1: Pharmacokinetic Parameter Tmax
NCT01696032 (11) [back to overview]CA-125 Levels
NCT01696032 (11) [back to overview]Duration of Response
NCT01696032 (11) [back to overview]Objective Response Rate
NCT01704287 (10) [back to overview]Best Overall Response (BOR) - Initial Treatment Period
NCT01704287 (10) [back to overview]Best Overall Response (BOR) - Switch-to-Pembrolizumab Treatment Period
NCT01704287 (10) [back to overview]Interim Overall Survival (OS) - Initial Treatment Period
NCT01704287 (10) [back to overview]Final Overall Survival (OS) - Initial Treatment Period
NCT01704287 (10) [back to overview]Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) - Overall Study
NCT01704287 (10) [back to overview]Duration of Response (DOR) - Initial Treatment Period
NCT01704287 (10) [back to overview]Number of Participants Who Experienced an Adverse Event (AE) - Overall Study
NCT01704287 (10) [back to overview]Overall Response Rate (ORR) - Initial Treatment Period
NCT01704287 (10) [back to overview]Progression-free Survival (PFS) - Initial Treatment Period
NCT01704287 (10) [back to overview]Final Overall Survival (OS) By Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Status - Initial Treatment Period
NCT01706939 (9) [back to overview]Change in MD Anderson Dysphagia Inventory (MDADI) From Baseline
NCT01706939 (9) [back to overview]Biomarkers Predictive of Failure
NCT01706939 (9) [back to overview]Change in Xerostomia Questionnaire (XQ)
NCT01706939 (9) [back to overview]Number of Participants With Acute Toxicity of Chemoradiotherapy (CRT)
NCT01706939 (9) [back to overview]Number of Participants With Local-regional Control
NCT01706939 (9) [back to overview]Change in European Organization for Research and Treatment of Cancer Questionnaire for Head and Neck (EORTC HN)
NCT01706939 (9) [back to overview]Change in MD Anderson Symptom Inventory Symptom Inventory and Severity (MDASI-HN SI and SS)
NCT01706939 (9) [back to overview]Number of Participants With Progression Free Survival (PFS)
NCT01706939 (9) [back to overview]Number of Participants With Overall Survival at 5 Years
NCT01711541 (2) [back to overview]Toxicity (Phase I and Phase II)
NCT01711541 (2) [back to overview]Dose Limiting Toxicity (Phase I)
NCT01715233 (3) [back to overview]CHFR Methylation Status
NCT01715233 (3) [back to overview]Overall Survival
NCT01715233 (3) [back to overview]Response
NCT01716195 (3) [back to overview]Number of Patients With Toxicity of Concurrent Chemoradiotherapy
NCT01716195 (3) [back to overview]Number of Participants With Overall Survival
NCT01716195 (3) [back to overview]Number of Participants With Progression-free Survival
NCT01721746 (7) [back to overview]Progression Free Survival (PFS)
NCT01721746 (7) [back to overview]Mean Change From Baseline in Health-related Quality of Life (HRQoL)
NCT01721746 (7) [back to overview]Objective Response Rate (ORR) by Baseline PD-L1 Expression
NCT01721746 (7) [back to overview]Objective Response Rate (ORR)
NCT01721746 (7) [back to overview]Overall Survival (OS)
NCT01721746 (7) [back to overview]Overall Survival (OS) by PD-L1 Negative
NCT01721746 (7) [back to overview]Overall Survival (OS) by PD-L1 Positive
NCT01722292 (9) [back to overview]Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells
NCT01722292 (9) [back to overview]Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
NCT01722292 (9) [back to overview]Phase 1b: Recommended Phase 2 Dose of LY2940680: Maximum Tolerated Dose (MTD)
NCT01722292 (9) [back to overview]Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Carboplatin and Etoposide at the Recommended Dose
NCT01722292 (9) [back to overview]Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for Etoposide and as AUC₀-₆ for Carboplatin at the Recommended Dose
NCT01722292 (9) [back to overview]Phase 1b and 2: Pharmacokinetics: Area Under the Curve ( AUC₀-₂₄) for LY2940680 and LSN3185556 at the Recommended Dose
NCT01722292 (9) [back to overview]Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of Carboplatin and Etoposide at the Recommended Dose
NCT01722292 (9) [back to overview]Phase 1b and 2: Pharmacokinetics: Time to Maximal Concentration (Tmax) of LY2940680 andLSN3185556 at the Recommended Dose
NCT01722292 (9) [back to overview]Phase 1b and 2: Pharmacokinetics (PK): Maximum Concentration (Cmax) of LY2940680, LSN3185556 at the Recommended Dose
NCT01732640 (2) [back to overview]Maximum Tolerated Dose (MTD) of Afatinib
NCT01732640 (2) [back to overview]Number of Participants With Dose Limiting Toxicities
NCT01763645 (7) [back to overview]Progression Rate
NCT01763645 (7) [back to overview]Partial Response Rate
NCT01763645 (7) [back to overview]Stabilization Rate
NCT01763645 (7) [back to overview]Area Under the Curve After the First Test Drug Administration
NCT01763645 (7) [back to overview]Complete Response Rate
NCT01763645 (7) [back to overview]Occurrence of Anti-bevacizumab Antibodies
NCT01763645 (7) [back to overview]Overall Response Rate
NCT01769391 (8) [back to overview]Overall Survival (OS)
NCT01769391 (8) [back to overview]Percent Change in Tumor Size (CTS)
NCT01769391 (8) [back to overview]Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR])
NCT01769391 (8) [back to overview]Percentage of Participants With Anti Necitumumab Antibodies
NCT01769391 (8) [back to overview]Progression-Free Survival
NCT01769391 (8) [back to overview]Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab
NCT01769391 (8) [back to overview]Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab
NCT01769391 (8) [back to overview]Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])
NCT01779050 (2) [back to overview]Death Rate
NCT01779050 (2) [back to overview]Number of Participants With Disease Recurrence
NCT01803282 (2) [back to overview]Percentage of Participants Experiencing Treatment-Emergent Adverse Events
NCT01803282 (2) [back to overview]Percentage of Participants Experiencing Laboratory Abnormalities
NCT01809210 (9) [back to overview]Objective Response Rate (ORR)
NCT01809210 (9) [back to overview]Percentage Change From Baseline at 6 Weeks in Target Lesion Size
NCT01809210 (9) [back to overview]Tmax,ss
NCT01809210 (9) [back to overview]Best Objective Response
NCT01809210 (9) [back to overview]Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib
NCT01809210 (9) [back to overview]Best Percentage Change From Baseline in Target Lesion Size
NCT01809210 (9) [back to overview]AUC (0-tau)
NCT01809210 (9) [back to overview]CL/F
NCT01809210 (9) [back to overview]Cmax,ss
NCT01818063 (1) [back to overview]Count of Participants That Achieve Pathologic Complete Response (PCR)
NCT01820754 (4) [back to overview]Number of Subjects Experiencing a Metastasis by Site of Metastasis
NCT01820754 (4) [back to overview]Percentage of Subjects With Detectable Circulating T Cells After Treatment
NCT01820754 (4) [back to overview]Feasibility and Tolerability of Neoadjuvant Chemotherapy Plus Ipilimumab and Surgery
NCT01820754 (4) [back to overview]Patterns of Pathologic Response and Response Evaluation Criteria in Solid Tumor (RECIST) Response
NCT01822496 (6) [back to overview]Percentage of Patients With Complete or Partial Response
NCT01822496 (6) [back to overview]Overall Survival
NCT01822496 (6) [back to overview]Number of Patients With Grade 3-5 Adverse Events
NCT01822496 (6) [back to overview]Progression-free Survival
NCT01822496 (6) [back to overview]Distant Progression-free Survival
NCT01822496 (6) [back to overview]Local-regional Progression-free Survival
NCT01827384 (3) [back to overview]Number of Participants With an Objective Response
NCT01827384 (3) [back to overview]Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
NCT01827384 (3) [back to overview]Proportion of Participants With 4 Month Progression-free Survival (PFS)
NCT01828099 (1) [back to overview]Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)
NCT01836029 (4) [back to overview]Comparison of the Objective Response Rate Between the Two Treatment Groups p
NCT01836029 (4) [back to overview]Comparison of Overall Survival (OS) Between the 2 Treatment Groups.
NCT01836029 (4) [back to overview]Comparison of Progression Free Survival (PFS) Between Treatment Groups Using irRECIST and Evaluated by Independent Radiology.
NCT01836029 (4) [back to overview]Comparison of Adverse Events (AEs) Between the Two Treatment Groups.
NCT01840579 (42) [back to overview]Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E
NCT01840579 (42) [back to overview]Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 4: Part D
NCT01840579 (42) [back to overview]Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E
NCT01840579 (42) [back to overview]Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1
NCT01840579 (42) [back to overview]Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E
NCT01840579 (42) [back to overview]Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D
NCT01840579 (42) [back to overview]Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A
NCT01840579 (42) [back to overview]Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E
NCT01840579 (42) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E
NCT01840579 (42) [back to overview]Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
NCT01840579 (42) [back to overview]Number of Participants Who Experienced at Least One Adverse Event (AE)
NCT01840579 (42) [back to overview]Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)
NCT01840579 (42) [back to overview]Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1
NCT01859741 (1) [back to overview]Phase 1b: To Determine the Maximum Tolerated Dose (MTD) of OMP-59R5 When Administered With Etoposide and Cisplatin or Carboplatin (Number of Subjects With DLTs)
NCT01862328 (8) [back to overview]Duration of Response
NCT01862328 (8) [back to overview]Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924
NCT01862328 (8) [back to overview]MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924
NCT01862328 (8) [back to overview]MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924
NCT01862328 (8) [back to overview]Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT01862328 (8) [back to overview]Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
NCT01862328 (8) [back to overview]Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
NCT01862328 (8) [back to overview]Percentage of Participants With Objective Response
NCT01867086 (2) [back to overview]Number of Alive Subjects
NCT01867086 (2) [back to overview]Immune Analysis in Blood
NCT01868022 (23) [back to overview]Number of Participants With the Abnormal Urinalysis Findings
NCT01868022 (23) [back to overview]Number of Participants With Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD)
NCT01868022 (23) [back to overview]Number of Participants With Hematology Change From Baseline With Respect to the Normal Range
NCT01868022 (23) [back to overview]Number of Participants With Clinically Significant Findings for 12-lead Electrocardiogram (ECG)
NCT01868022 (23) [back to overview]Number of Participants With Dose Delays
NCT01868022 (23) [back to overview]Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range
NCT01868022 (23) [back to overview]Number of Participants With Best Response
NCT01868022 (23) [back to overview]Number of Participants With Abnormal Echocardiogram (ECHO) Findings
NCT01868022 (23) [back to overview]Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
NCT01868022 (23) [back to overview]Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range
NCT01868022 (23) [back to overview]Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range
NCT01868022 (23) [back to overview]Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)
NCT01868022 (23) [back to overview]Number of Participants With Dose-Limiting Toxicities (DLT)
NCT01868022 (23) [back to overview]Number of Participants Withdrew Due to AEs
NCT01868022 (23) [back to overview]Change From Baseline in Forced Vital Capacity (FVC) in of Arm C Participants With Malignant Pleural Mesothelioma (MPM)
NCT01868022 (23) [back to overview]Change From Baseline in Forced Vital Capacity (FVC) in of Arm C Participants With Malignant Pleural Mesothelioma (MPM)
NCT01868022 (23) [back to overview]Change From Baseline in Forced Vital Capacity (FVC) in of Arm C Participants With Malignant Pleural Mesothelioma (MPM)
NCT01868022 (23) [back to overview]Treatment Duration With GSK3052230
NCT01868022 (23) [back to overview]Progression Free Survival (PFS) as Assessed by Investigator
NCT01868022 (23) [back to overview]Number of Participants With Overall Response Rate (ORR)
NCT01868022 (23) [back to overview]Number of Participants With Dose Reduction
NCT01868022 (23) [back to overview]Change From Baseline in Heart Rate
NCT01868022 (23) [back to overview]Change From Baseline in Temperature
NCT01881230 (7) [back to overview]Kaplan-Meier Estimates of Overall Survival
NCT01881230 (7) [back to overview]Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.
NCT01881230 (7) [back to overview]Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs
NCT01881230 (7) [back to overview]Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.
NCT01881230 (7) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs)
NCT01881230 (7) [back to overview]Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions)
NCT01881230 (7) [back to overview]Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy
NCT01898494 (5) [back to overview]Proportion of Patients With Grade III or IV Oropharyngeal Bleeding or Positive Margins
NCT01898494 (5) [back to overview]Progression-free Survival Rate at 2 Years
NCT01898494 (5) [back to overview]Swallowing Function Before Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
NCT01898494 (5) [back to overview]Swallowing Function After Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)
NCT01898494 (5) [back to overview]Quality of Life (QOL) at 6 Months After Treatment Assessed by Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-HN) Total Score
NCT01916109 (1) [back to overview]Pathologic Complete Response Rate (
NCT01959490 (1) [back to overview]Number of Patients With a Pathological Complete Response (pCR) Who Received Targeted Therapy With Trastuzumab and Pertuzumab or Bevacizumab Predicted by Genomically-derived Molecular Subtypes.
NCT01959698 (6) [back to overview]Overall Survival
NCT01959698 (6) [back to overview]MTD Defined as the Dose of Carfilzomib Added to Standard R-ICE Chemotherapy Which, if Exceeded, Would Put the Patient at an Undesirable Risk of Medically Unacceptable Dose-limiting Toxicities (Phase I)
NCT01959698 (6) [back to overview]Overall Response Rate (PR + CR)
NCT01959698 (6) [back to overview]Complete Response Rate According to the International Working Group Response Criteria as Reported by the Revised Cheson Criteria
NCT01959698 (6) [back to overview]Progression-free Survival
NCT01959698 (6) [back to overview]Toxicity of the Addition of Carfilzomib to R-ICE at the MTD, Assessed by the CTEP Version 4.0 of the NCI CTCAE
NCT01966003 (6) [back to overview]Duration of Response
NCT01966003 (6) [back to overview]Percentage of Participants With an Objective Response
NCT01966003 (6) [back to overview]Progression-free Survival
NCT01966003 (6) [back to overview]Number of Participants Who Developed Anti-drug Antibodies
NCT01966003 (6) [back to overview]Number of Participants With Adverse Events
NCT01966003 (6) [back to overview]Overall Survival
NCT01982955 (44) [back to overview]Phase 1b: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time AUC (0-t) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Average Observed Plasma Concentration (Cavg) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Death and Reasons
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment-Related TEAEs and Treatment-Related Serious TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Grade 3/4 Treatment-Emergent Adverse Events (TEAEs) and Grade 3/4 Treatment-Related TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI-CTCAE) Version 4.03
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Clinically Significant Abnormalities in Vital Signs
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Serious TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03
NCT01982955 (44) [back to overview]Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Death and Reasons
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent Adverse Events (TEAEs) and >= Grade 3 Treatment-Related TEAEs According to National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings
NCT01982955 (44) [back to overview]Phase 1b: Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
NCT01982955 (44) [back to overview]Phase 2 (Non-Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
NCT01982955 (44) [back to overview]Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)
NCT01982955 (44) [back to overview]Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Investigator
NCT01982955 (44) [back to overview]Phase 2 (Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
NCT01982955 (44) [back to overview]Phase 2 (Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
NCT01982955 (44) [back to overview]Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)
NCT01982955 (44) [back to overview]Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator
NCT01982955 (44) [back to overview]Phase 2: (Non-Randomized Part Only): Overall Survival (OS) Time
NCT01982955 (44) [back to overview]Phase 2: (Randomized Part Only): Overall Survival (OS) Time
NCT01982955 (44) [back to overview]Phase 2: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT)
NCT01982955 (44) [back to overview]Phase 1b: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Apparent Total Body Clearance From Plasma (CL/F) of Tepotinib and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Apparent Terminal Half-Life (t1/2) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib, Its Metabolites and Gefitinib
NCT01982955 (44) [back to overview]Phase 2: Time-to-Symptom Progression (TTSP)
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation
NCT01982955 (44) [back to overview]Phase 2: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation
NCT01982955 (44) [back to overview]Phase 2 (Non-Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants Experiencing at Least One Dose Limiting Toxicity (DLT)
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Clinically Significant Abnormalities in Vital Signs
NCT01982955 (44) [back to overview]Phase 1b: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2
NCT01982955 (44) [back to overview]Phase 1b: Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria
NCT01982955 (44) [back to overview]Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/F) of Tepotinib, Its Metabolites and Gefitinib
NCT01987232 (5) [back to overview]Overall Response Rate
NCT01987232 (5) [back to overview]Number of Participants With Dose-limiting Toxicities
NCT01987232 (5) [back to overview]Duration of Response
NCT01987232 (5) [back to overview]Number of Participants With Adverse Events (AEs)
NCT01987232 (5) [back to overview]Progression-free Survival
NCT01998919 (7) [back to overview]Overall Survival
NCT01998919 (7) [back to overview]Duration of Response
NCT01998919 (7) [back to overview]Percentage of Participants With Confirmed CR or PR as Assessed by RECIST
NCT01998919 (7) [back to overview]Percentage of Participants With Non-Progression at Week 16 as Assessed by RECIST
NCT01998919 (7) [back to overview]Percentage of Participants With Non-Progression at Week 8 as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)
NCT01998919 (7) [back to overview]Progression-Free Survival (PFS)
NCT01998919 (7) [back to overview]Time to Progression
NCT02003209 (5) [back to overview]Percentage of Participants With Cardiac Toxicity Categorized According to National Cancer Institute CTCAE Version 4.0
NCT02003209 (5) [back to overview]Median Percentage of Tumor-infiltrating Lymphocytes (sTILS)
NCT02003209 (5) [back to overview]Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes by Menopausal Status
NCT02003209 (5) [back to overview]Percent of Patients With Pathologic Complete Response (pCR) in the Breast
NCT02003209 (5) [back to overview]Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes
NCT02004093 (13) [back to overview]Kaplan-Meier Probability of Being Alive at 1 Year
NCT02004093 (13) [back to overview]Kaplan-Meier Probability of Being Progression Free at 1 Year
NCT02004093 (13) [back to overview]Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year
NCT02004093 (13) [back to overview]Kaplan-Meier Probability of No Disease or Progression at 1 Year
NCT02004093 (13) [back to overview]Overall Survival
NCT02004093 (13) [back to overview]Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements
NCT02004093 (13) [back to overview]Percentage of Participants With Disease Progression or Death
NCT02004093 (13) [back to overview]Progression-Free Survival
NCT02004093 (13) [back to overview]Time to Progressive Disease
NCT02004093 (13) [back to overview]Time To Response
NCT02004093 (13) [back to overview]Percentage of Participants Who Died
NCT02004093 (13) [back to overview]Duration of Response
NCT02004093 (13) [back to overview]Percentage of Participants With Disease Progression
NCT02017964 (5) [back to overview]Event-free Survival (EFS)
NCT02017964 (5) [back to overview]Overall Survival (OS)
NCT02017964 (5) [back to overview]Percentage of Patients With Responses at 189 Days
NCT02017964 (5) [back to overview]Percentage of Patients With Responses at 273 Days
NCT02017964 (5) [back to overview]Progression-free Survival (PFS)
NCT02018458 (2) [back to overview]Safety of DC Vaccine Combined With Chemotherapy
NCT02018458 (2) [back to overview]Disease-free Survival
NCT02018861 (27) [back to overview]Part 3: Tmax of Parsaclisib Monotherapy
NCT02018861 (27) [back to overview]Part 3: Cmin of Parsaclisib Monotherapy
NCT02018861 (27) [back to overview]Part 3: Cmax of Parsaclisib Monotherapy
NCT02018861 (27) [back to overview]Part 3: AUC0-τ of Parsaclisib Monotherapy
NCT02018861 (27) [back to overview]Part 3: AUC0-t of Parsaclisib Monotherapy
NCT02018861 (27) [back to overview]Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT
NCT02018861 (27) [back to overview]Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT
NCT02018861 (27) [back to overview]Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT
NCT02018861 (27) [back to overview]Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT
NCT02018861 (27) [back to overview]Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT
NCT02018861 (27) [back to overview]Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT
NCT02018861 (27) [back to overview]Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT
NCT02018861 (27) [back to overview]Tmax of Itacitinib in Combination With Parsaclisib
NCT02018861 (27) [back to overview]Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL
NCT02018861 (27) [back to overview]Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM
NCT02018861 (27) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs)
NCT02018861 (27) [back to overview]Cmin of Itacitinib in Combination With Parsaclisib
NCT02018861 (27) [back to overview]Cmax of Itacitinib in Combination With Parsaclisib
NCT02018861 (27) [back to overview]AUC0-τ of Itacitinib in Combination With Parsaclisib
NCT02018861 (27) [back to overview]AUC0-t of Itacitinib in Combination With Parsaclisib
NCT02018861 (27) [back to overview]Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants
NCT02018861 (27) [back to overview]Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
NCT02018861 (27) [back to overview]Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib
NCT02018861 (27) [back to overview]Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib
NCT02018861 (27) [back to overview]Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib
NCT02018861 (27) [back to overview]Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib
NCT02018861 (27) [back to overview]Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT
NCT02027428 (11) [back to overview]Time to Confirmed Response During Induction and Over the Entire Study
NCT02027428 (11) [back to overview]Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study
NCT02027428 (11) [back to overview]Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period
NCT02027428 (11) [back to overview]Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study
NCT02027428 (11) [back to overview]Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) Over Entire Study
NCT02027428 (11) [back to overview]Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) In Maintenance Beyond the Response in Induction
NCT02027428 (11) [back to overview]Kaplan-Meier Estimate of Progression-Free Survival (PFS) Over Entire Study
NCT02027428 (11) [back to overview]Kaplan-Meier Estimate of Progression-Free Survival (PFS) From Randomization Into Maintenance
NCT02027428 (11) [back to overview]Kaplan-Meier Estimate of Overall Survival (OS) Over Entire Study
NCT02027428 (11) [back to overview]Kaplan-Meier Estimate of Overall Survival (OS) From Randomization Into Maintenance
NCT02027428 (11) [back to overview]Kaplan-Meier Estimate for Duration of Response Over the Entire Study
NCT02035345 (2) [back to overview]Number of Participants With Carboplatin Infusion Hypersensitivity Reactions Using a Slowed Carboplatin Infusion Program
NCT02035345 (2) [back to overview]Number of Patients With Carboplatin Reactions of Different Severity
NCT02039674 (6) [back to overview]Part 2 Cohorts G+ and G-: Overall Survival (OS)
NCT02039674 (6) [back to overview]Part 2 Cohorts G+ and G-: Objective Response Rate (ORR)
NCT02039674 (6) [back to overview]Part 2 Cohorts G+ and G-: Duration of Response (DOR)
NCT02039674 (6) [back to overview]Part 2 Cohorts D4 and H: Objective Response Rate (ORR)
NCT02039674 (6) [back to overview]All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
NCT02039674 (6) [back to overview]Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS)
NCT02041533 (6) [back to overview]Progression-Free Survival in Participants With PD-L1 Expression >= 5%
NCT02041533 (6) [back to overview]Progression-Free Survival in All Randomized Participants
NCT02041533 (6) [back to overview]Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5%
NCT02041533 (6) [back to overview]Overall Survival in All Randomized Participants
NCT02041533 (6) [back to overview]Disease-related Symptom Improvement Rate by Week 12
NCT02041533 (6) [back to overview]Overall Survival in Participants With PD-L1 Expression >= 5%
NCT02065687 (8) [back to overview]Level of Obesity
NCT02065687 (8) [back to overview]Duration of Response by Treatment
NCT02065687 (8) [back to overview]Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4
NCT02065687 (8) [back to overview]Proportion of Patients Responding to Therapy
NCT02065687 (8) [back to overview]Progression-free Survival (PFS) (Phase II)
NCT02065687 (8) [back to overview]Progression Free Survival (PFS) (Phase III)
NCT02065687 (8) [back to overview]Overall Survival (OS) (Phase II)
NCT02065687 (8) [back to overview]Overall Survival (OS) (Phase II and III)
NCT02073968 (7) [back to overview]Metabolic Response of All Pulmonary Lesions and Thoracic Lymph Nodes
NCT02073968 (7) [back to overview]Lung Cancer Cause-specific Survival
NCT02073968 (7) [back to overview]Locoregional Progression-free Survival Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
NCT02073968 (7) [back to overview]Incidence of Grade >= 3 Treatment-related Toxicity, Scored Using CTCAE, v. 4
NCT02073968 (7) [back to overview]Progression-free Survival Assessed Using the RECIST Criteria
NCT02073968 (7) [back to overview]Incidence of Grade >= 2 Radiation-induced Lung Toxicity, Scored Using Common Terminology Criteria for Adverse Events (CTCAE), Version (v.) 4
NCT02073968 (7) [back to overview]Overall Survival
NCT02083679 (2) [back to overview]Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death
NCT02083679 (2) [back to overview]Number of Subjects With Dose Limiting Toxicities (DLTs)
NCT02087241 (2) [back to overview]Assess the Disease Control Rate in Each Treatment Arm
NCT02087241 (2) [back to overview]Assess the Objective Response Rates in Each Arm
NCT02098343 (2) [back to overview]Phase Ib and II: Progression Free Survival (PFS)
NCT02098343 (2) [back to overview]Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen
NCT02122770 (17) [back to overview]Part A: Volume of Distribution (Vz) for MLN4924
NCT02122770 (17) [back to overview]Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
NCT02122770 (17) [back to overview]Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
NCT02122770 (17) [back to overview]Part A Tmax: Time to Reach the Cmax for MLN4924
NCT02122770 (17) [back to overview]Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Fluconazole
NCT02122770 (17) [back to overview]Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Itraconazole
NCT02122770 (17) [back to overview]Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Fluconazole
NCT02122770 (17) [back to overview]Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Itraconazole
NCT02122770 (17) [back to overview]Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Fluconazole
NCT02122770 (17) [back to overview]Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Itraconazole
NCT02122770 (17) [back to overview]Part B: Duration of Response
NCT02122770 (17) [back to overview]Part B: Percentage of Participants With Objective Response
NCT02122770 (17) [back to overview]Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)
NCT02122770 (17) [back to overview]Number of Participants With Clinically Significant Change From Baseline in Body Weight Measurements
NCT02122770 (17) [back to overview]Part A: Terminal Phase Elimination Half-life (T1/2) for MLN4924
NCT02122770 (17) [back to overview]Part A: Plasma Clearance (CLp) for MLN4924
NCT02122770 (17) [back to overview]Part A: Blood to Plasma (B/P) Concentration Ratio for MLN4924
NCT02124707 (4) [back to overview]Incidence of Adverse Events
NCT02124707 (4) [back to overview]Head and Neck Quality of Life Assessments
NCT02124707 (4) [back to overview]Median Progression Free Survival
NCT02124707 (4) [back to overview]Median Overall Survival
NCT02124902 (1) [back to overview]Pathological Complete Response (pCR) Rate
NCT02126969 (3) [back to overview]3-year Overall Survival
NCT02126969 (3) [back to overview]Primary Site Complete Response Rate
NCT02126969 (3) [back to overview]Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy.
NCT02131064 (22) [back to overview]Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales
NCT02131064 (22) [back to overview]Percentage of Participants by Response for Skin Problem Single Items
NCT02131064 (22) [back to overview]Percentage of Participants by Response for Neuropathy Single Item
NCT02131064 (22) [back to overview]Percentage of Participants by Response for Hair Loss Single Item
NCT02131064 (22) [back to overview]Minimum Observed Serum Concentration (Cmin) of Trastuzumab
NCT02131064 (22) [back to overview]Maximum Observed Serum Concentration (Cmax) of Trastuzumab
NCT02131064 (22) [back to overview]Cmin of Trastuzumab Emtansine and Total Trastuzumab
NCT02131064 (22) [back to overview]Cmax of Trastuzumab Emtansine and Total Trastuzumab
NCT02131064 (22) [back to overview]Time to Clinically Meaningful Deterioration in GHS/QoL Score
NCT02131064 (22) [back to overview]Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples
NCT02131064 (22) [back to overview]Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score
NCT02131064 (22) [back to overview]Percentage of Participants Who Received Breast-Conserving Surgery (BCS)
NCT02131064 (22) [back to overview]Overall Survival
NCT02131064 (22) [back to overview]Invasive Disease-free Survival (IDFS)
NCT02131064 (22) [back to overview]Event-Free Survival
NCT02131064 (22) [back to overview]Time to Clinically Meaningful Deterioration in Function Subscale
NCT02131064 (22) [back to overview]Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1)
NCT02131064 (22) [back to overview]Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations
NCT02131064 (22) [back to overview]Percentage of Participants With Selected Adverse Events (AEs)
NCT02131064 (22) [back to overview]Percentage of Participants With ATA to Trastuzumab
NCT02131064 (22) [back to overview]Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1
NCT02131064 (22) [back to overview]Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales
NCT02142738 (3) [back to overview]Progression Free Survival (PFS) Rate at Month 6
NCT02142738 (3) [back to overview]Overall Survival (OS) Rate
NCT02142738 (3) [back to overview]Objective Response Rate (ORR)
NCT02151149 (10) [back to overview]Percentage of Participants With at Least 1 Treatment Emergent Adverse Event With Action Taken as Study Drug Withdrawn
NCT02151149 (10) [back to overview]Number of Participants With Treatment Emergent Adverse Events During the Treatment Period
NCT02151149 (10) [back to overview]Percentage of Participants With Either Peripheral Neuropathy ≥ Grade 2 or Myelosuppression Adverse Events (AEs) ≥ Grade 3 Based on Local Laboratory Values
NCT02151149 (10) [back to overview]Percentage of Participants With a Dose Delay During the Entire Study
NCT02151149 (10) [back to overview]Dose Intensity Per Week of Carboplatin During the Entire Study
NCT02151149 (10) [back to overview]Percentage of Participants With Dose Reductions During the Entire Study
NCT02151149 (10) [back to overview]Dose Intensity Per Week of Nab-Paclitaxel During the Entire Study
NCT02151149 (10) [back to overview]Kaplan Meier Estimate of Overall Survival (OS)
NCT02151149 (10) [back to overview]Kaplan Meier Estimate of Progression-Free Survival (PFS)
NCT02151149 (10) [back to overview]Percentage of Participants Who Achieved a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST 1.1 Criteria
NCT02163694 (1) [back to overview]Progression-Free Survival (PFS)
NCT02186847 (5) [back to overview]Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events
NCT02186847 (5) [back to overview]Percentage of Participants With Local-regional Progression
NCT02186847 (5) [back to overview]Percentage of Participants With Distant Metastases
NCT02186847 (5) [back to overview]Percentage of Participants Alive Without Progression (Progression-free Survival)
NCT02186847 (5) [back to overview]Percentage of Participants Alive (Overall Survival)
NCT02187744 (6) [back to overview]Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.
NCT02187744 (6) [back to overview]Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.
NCT02187744 (6) [back to overview]Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.
NCT02187744 (6) [back to overview]Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.
NCT02187744 (6) [back to overview]Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.
NCT02187744 (6) [back to overview]Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.
NCT02220894 (11) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
NCT02220894 (11) [back to overview]Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%
NCT02220894 (11) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
NCT02220894 (11) [back to overview]Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%
NCT02220894 (11) [back to overview]Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%
NCT02220894 (11) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
NCT02220894 (11) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
NCT02220894 (11) [back to overview]Number of Participants Who Experienced At Least One Adverse Event (AE)
NCT02220894 (11) [back to overview]Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
NCT02220894 (11) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
NCT02220894 (11) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
NCT02227199 (4) [back to overview]Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy
NCT02227199 (4) [back to overview]2 Year Progression-free Survival
NCT02227199 (4) [back to overview]Percentage of Patients That Achieve a Complete Remission Following Study Treatment
NCT02227199 (4) [back to overview]2 Year Overall Survival
NCT02258659 (7) [back to overview]Rates of Acute Toxicity, Determined by Incidence of Mucositis, Xerostomia, Anorexia, Weight Loss, Dermatitis and G-tube Placement
NCT02258659 (7) [back to overview]Rates of Late Toxicity, Determined by Incidence of Xerostomia, Dental Decay, Osteroradionecrosis, G-tube Dependency, Tracheostomy Placement and Dysphagia
NCT02258659 (7) [back to overview]Cancer-specific Survival
NCT02258659 (7) [back to overview]Overall Survival
NCT02258659 (7) [back to overview]Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1
NCT02258659 (7) [back to overview]Rate of Pathologic Complete Response (PCR) on Post Treatment Biopsy/Surgery, Evaluated Using RECIST v1.1
NCT02258659 (7) [back to overview]Clinical Complete Response by Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI) Only
NCT02264990 (6) [back to overview]Overall Survival in All Participants
NCT02264990 (6) [back to overview]Progression Free Survival (PFS) in All Participants
NCT02264990 (6) [back to overview]Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup
NCT02264990 (6) [back to overview]Objective Response Rate (ORR) in All Participants
NCT02264990 (6) [back to overview]Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup
NCT02264990 (6) [back to overview]Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup
NCT02272790 (23) [back to overview]The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Adavosertib by Maximum CTCAE Grade
NCT02272790 (23) [back to overview]The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) Related to Chemotherapy by Maximum CTCAE Grade
NCT02272790 (23) [back to overview]Multiple Dose Adavosertib Cmax
NCT02272790 (23) [back to overview]Progression Free Survival (Median, 80% CI)
NCT02272790 (23) [back to overview]Serious Adverse Events
NCT02272790 (23) [back to overview]Treatment-Related Adverse Events Related to Chemotherapy Leading to Dose Reduction
NCT02272790 (23) [back to overview]Serious Adverse Events Leading to Death
NCT02272790 (23) [back to overview]Treatment-Related Adverse Events Related to Adavosertib Leading to Dose Reduction
NCT02272790 (23) [back to overview]Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Discontinuation
NCT02272790 (23) [back to overview]Treatment-Related Adverse Events Related to Adavosertib Leading to Treatment Interruption
NCT02272790 (23) [back to overview]Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Discontinuation
NCT02272790 (23) [back to overview]Overall Survival (Median, 95% CI)
NCT02272790 (23) [back to overview]Single Dose Adavosertib Cmax
NCT02272790 (23) [back to overview]Overall Survival (Median, 80% CI)
NCT02272790 (23) [back to overview]Objective Response Rate (ORR)
NCT02272790 (23) [back to overview]Single Dose Adavosertib Tmax
NCT02272790 (23) [back to overview]Disease Control Rate (DCR)
NCT02272790 (23) [back to overview]Duration of Response (DoR)
NCT02272790 (23) [back to overview]Progression Free Survival (Median, 95% CI)
NCT02272790 (23) [back to overview]Multiple Dose Adavosertib Tmax
NCT02272790 (23) [back to overview]Gynecologic Cancer Intergroup (GCIG) CA-125 Response
NCT02272790 (23) [back to overview]The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.
NCT02272790 (23) [back to overview]Treatment-Related Adverse Events Related to Chemotherapy Leading to Treatment Interruption
NCT02272816 (1) [back to overview]2 - Year Progression Free Survival
NCT02278250 (66) [back to overview]Part A: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344
NCT02278250 (66) [back to overview]Part A2: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
NCT02278250 (66) [back to overview]Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
NCT02278250 (66) [back to overview]Part A2: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
NCT02278250 (66) [back to overview]Part B1: Apparent Clearance (CL/f) of M4344
NCT02278250 (66) [back to overview]Part B1: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
NCT02278250 (66) [back to overview]Part B1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
NCT02278250 (66) [back to overview]Part B1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
NCT02278250 (66) [back to overview]Part B1: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
NCT02278250 (66) [back to overview]Part B1: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
NCT02278250 (66) [back to overview]Part B1: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
NCT02278250 (66) [back to overview]Part B1: Maximum Observed Plasma Concentration (Cmax) of M4344
NCT02278250 (66) [back to overview]Part B1: Maximum Tolerated Dose (MTD) of M4344 (Monotherapy) Administered in Combination With Carboplatin
NCT02278250 (66) [back to overview]Part B1: Number of Participants With Clinically Relevant Findings in Vital Signs
NCT02278250 (66) [back to overview]Part B1: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
NCT02278250 (66) [back to overview]Part B1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
NCT02278250 (66) [back to overview]Part B1: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
NCT02278250 (66) [back to overview]Part B1: Terminal Elimination Half-Life (T1/2) of M4344
NCT02278250 (66) [back to overview]Part B1:Time to Reach Maximum Plasma Concentration (Tmax) of M4344
NCT02278250 (66) [back to overview]Part C: Number of Participants With Clinically Relevant Findings in Vital Signs
NCT02278250 (66) [back to overview]Part C: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
NCT02278250 (66) [back to overview]Part C: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator
NCT02278250 (66) [back to overview]Part C: Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Investigator
NCT02278250 (66) [back to overview]Part A: Apparent Clearance (CL/f) of M4344
NCT02278250 (66) [back to overview]Part A: Apparent Clearance (CL/f) of M4344
NCT02278250 (66) [back to overview]Part A: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
NCT02278250 (66) [back to overview]Part A: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
NCT02278250 (66) [back to overview]Part A: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
NCT02278250 (66) [back to overview]Part A: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
NCT02278250 (66) [back to overview]Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
NCT02278250 (66) [back to overview]Part A: Maximum Observed Plasma Concentration (Cmax) of M4344
NCT02278250 (66) [back to overview]Part A: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)
NCT02278250 (66) [back to overview]Part A: Terminal Elimination Half-Life (T1/2) of M4344
NCT02278250 (66) [back to overview]Part A: Terminal Elimination Half-Life (T1/2) of M4344
NCT02278250 (66) [back to overview]Part A: Maximum Tolerated Dose (MTD) of M4344 Administered Twice Weekly (BIW)
NCT02278250 (66) [back to overview]Part C: Overall Survival (OS)
NCT02278250 (66) [back to overview]Part C: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related AEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
NCT02278250 (66) [back to overview]Part C: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)
NCT02278250 (66) [back to overview]Part C: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
NCT02278250 (66) [back to overview]Part A: Number of Participants With Clinically Relevant Findings in Vital Signs
NCT02278250 (66) [back to overview]Part A: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
NCT02278250 (66) [back to overview]Part A2: Apparent Clearance (CL/f) of M4344
NCT02278250 (66) [back to overview]Part A2: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344
NCT02278250 (66) [back to overview]Part A2: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344
NCT02278250 (66) [back to overview]Part A: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
NCT02278250 (66) [back to overview]Part A: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
NCT02278250 (66) [back to overview]Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
NCT02278250 (66) [back to overview]Part A: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
NCT02278250 (66) [back to overview]Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve (Racc [AUC]) of M4344
NCT02278250 (66) [back to overview]Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344
NCT02278250 (66) [back to overview]Part A2: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344
NCT02278250 (66) [back to overview]Part A2: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344
NCT02278250 (66) [back to overview]Part A2: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344
NCT02278250 (66) [back to overview]Part A2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
NCT02278250 (66) [back to overview]Part A2: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
NCT02278250 (66) [back to overview]Part A2: Maximum Tolerated Dose (MTD) of M4344 Administered With a Dose Dense Schedule
NCT02278250 (66) [back to overview]Part A2: Number of Participants With Clinically Relevant Findings in Vital Signs
NCT02278250 (66) [back to overview]Part A2: Maximum Observed Plasma Concentration (Cmax) of M4344
NCT02278250 (66) [back to overview]Part A2: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)
NCT02278250 (66) [back to overview]Part A2: Terminal Elimination Half-Life (T1/2) of M4344
NCT02278250 (66) [back to overview]Part A2: Time to Reach Maximum Plasma Concentration (Tmax) of M4344
NCT02278250 (66) [back to overview]Part B1: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)
NCT02278250 (66) [back to overview]Part A2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)
NCT02278250 (66) [back to overview]Part A: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344
NCT02278250 (66) [back to overview]Part A: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344
NCT02278250 (66) [back to overview]Part A: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344
NCT02279732 (3) [back to overview]Progression-free Survival (PFS) Among All Randomized Particiapants Who Received at Least One Dose of Blinded Study Therapy Using Modified World Health Organization (mWHO) Criteria
NCT02279732 (3) [back to overview]Overall Survival of All Randomized Participants
NCT02279732 (3) [back to overview]Overall Survival (OS) of All Randomized Participants Who Received at Least One Dose of Blinded Study Therapy
NCT02289456 (13) [back to overview]Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST 1.1 Guidelines
NCT02289456 (13) [back to overview]Percentage of Protocol Dose
NCT02289456 (13) [back to overview]Kaplan Meier Estimate of Progression-Free Survival (PFS)
NCT02289456 (13) [back to overview]Dose Intensity of Nab-Paclitaxel During the Entire Study
NCT02289456 (13) [back to overview]Kaplan Meier Estimate of Overall Survival (OS)
NCT02289456 (13) [back to overview]Kaplan Meier Estimate of Duration of Response
NCT02289456 (13) [back to overview]Percentage of Participants With Dose Reductions During the Entire Study
NCT02289456 (13) [back to overview]Number of Participants With TEAEs During the Induction and Monotherapy Periods
NCT02289456 (13) [back to overview]Time to Response
NCT02289456 (13) [back to overview]Percentage of Participants Who Discontinued Study Treatment During the Induction Period Due to Treatment Emergent Adverse Events (TEAEs).
NCT02289456 (13) [back to overview]Percentage of Participants Who Discontinued Study Treatment During the Induction Period (Discontinuation Rate)
NCT02289456 (13) [back to overview]Dose Intensity of Carboplatin During the Entire Study
NCT02289456 (13) [back to overview]Percentage of Participants Who Achieved a Complete Response or Partial Response or Continued Stable Disease (Disease Control Rate)
NCT02289690 (20) [back to overview]Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
NCT02289690 (20) [back to overview]Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 2: Progression-free Survival
NCT02289690 (20) [back to overview]Phase 2: Overall Survival
NCT02289690 (20) [back to overview]Phase 2: Objective Response Rate
NCT02289690 (20) [back to overview]Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Number of Participants With Adverse Events
NCT02289690 (20) [back to overview]Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib
NCT02289690 (20) [back to overview]Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib
NCT02289690 (20) [back to overview]Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib
NCT02311907 (9) [back to overview]Times to Onset of CTCAE Grade 2+ PN
NCT02311907 (9) [back to overview]Change in Patient Reported Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Ovarian (FACT-O) and Patient Daily-symptom Questionnaires Over Time.
NCT02311907 (9) [back to overview]Paclitaxel Acute Pain Syndrome Incidence and Severity Between GSH and Placebo Arms
NCT02311907 (9) [back to overview]Paclitaxel/Carboplatin (PC) Induced Peripheral Neuropathy as Assessed by EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer (EORTC), Quality of Life (QLQ), Chemotherapy Induced Peripheral Neuropathy 20 (CIPN20)).
NCT02311907 (9) [back to overview]Percentage of Patients Delaying PC Chemotherapy Secondary to PN
NCT02311907 (9) [back to overview]Recurrence-free Survival (for Patients Without Clinical Evidence of Disease)
NCT02311907 (9) [back to overview]Times to Onset of CTCAE Grade 3+ PN
NCT02311907 (9) [back to overview]Percentage of Patients Undergoing Dose Reductions Secondary to PCI PN
NCT02311907 (9) [back to overview]Percentage of Patients With Grade 2+ and Grade 3+ Paclitaxel/Carboplatin-induced (PCI) Peripheral Neuropathy (PN) According to the Common Terminology Criteria for Adverse Events (CTCAE) Neuropathy Scale
NCT02315196 (1) [back to overview]Rate of Pathologic Complete Response (pCR) Based on Response Evaluation Criteria in Solid Tumors Criteria
NCT02319486 (1) [back to overview]Event Free Survival Rate
NCT02328105 (6) [back to overview]Progression Free Survival
NCT02328105 (6) [back to overview]Number of Subjects With Stable Disease or Response
NCT02328105 (6) [back to overview]Overall Survival
NCT02328105 (6) [back to overview]Number of Participants With a Response
NCT02328105 (6) [back to overview]Duration of Response
NCT02328105 (6) [back to overview]Duration of Disease Control
NCT02337530 (1) [back to overview]Progression Free Survival
NCT02341456 (39) [back to overview]Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
NCT02341456 (39) [back to overview]Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2)
NCT02341456 (39) [back to overview]Time to Maximum Plasma Concentration (Tmax) of AZD1775 at Steady State When Given in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02341456 (39) [back to overview]Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term
NCT02341456 (39) [back to overview]Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy
NCT02341456 (39) [back to overview]Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02341456 (39) [back to overview]Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin
NCT02341456 (39) [back to overview]Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin
NCT02341456 (39) [back to overview]Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2)
NCT02341456 (39) [back to overview]Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
NCT02341456 (39) [back to overview]Area Under the Plasma Concentration-time Curve (AUC0-t) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin
NCT02341456 (39) [back to overview]Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) at Steady State for AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02341456 (39) [back to overview]Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose Administration of AZD1775 Monotherapy
NCT02341456 (39) [back to overview]Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02341456 (39) [back to overview]Duration of Response
NCT02341456 (39) [back to overview]Number of Patients With an Objective Response
NCT02341456 (39) [back to overview]Best Overall Response
NCT02341456 (39) [back to overview]Peak Plasma Concentration (Cmax) of AZD1775 at Steady State When Given in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02341456 (39) [back to overview]Peak Plasma Concentration (Cmax) of AZD1775 Following Oral Dose of AZD1775 in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02341456 (39) [back to overview]Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term
NCT02341456 (39) [back to overview]Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term
NCT02341456 (39) [back to overview]Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term
NCT02341456 (39) [back to overview]Number of Patients With Treatment-Emergent Adverse Events
NCT02341456 (39) [back to overview]Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
NCT02341456 (39) [back to overview]Number of Treatment-Emergent Adverse Events (TEAE)
NCT02341456 (39) [back to overview]Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02341456 (39) [back to overview]Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy
NCT02341456 (39) [back to overview]Number of Patients With Clinical Benefit
NCT02341456 (39) [back to overview]Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin.
NCT02341456 (39) [back to overview]Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
NCT02341456 (39) [back to overview]Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
NCT02341456 (39) [back to overview]Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.
NCT02341456 (39) [back to overview]Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy
NCT02341456 (39) [back to overview]Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin
NCT02341456 (39) [back to overview]Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2)
NCT02341456 (39) [back to overview]Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2)
NCT02341456 (39) [back to overview]Percentage of Patients With an Objective Response
NCT02341456 (39) [back to overview]Percentage of Patients With Clinical Benefit
NCT02341456 (39) [back to overview]Plasma Concentration of AZD1775 8 Hours After Administration (C8h) at Steady State in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)
NCT02358031 (40) [back to overview]Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Overall Survival (OS) in All Participants
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Number of Participants Who Discontinued Study Drug Due to an AE
NCT02358031 (40) [back to overview]Number of Participants Experiencing an Adverse Event (AE)
NCT02358031 (40) [back to overview]Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
NCT02358031 (40) [back to overview]Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
NCT02358031 (40) [back to overview]Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Mono vs Control: OS in All Participants
NCT02358031 (40) [back to overview]Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants
NCT02358031 (40) [back to overview]Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants
NCT02358031 (40) [back to overview]Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method)
NCT02358031 (40) [back to overview]Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method)
NCT02358031 (40) [back to overview]Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method)
NCT02358031 (40) [back to overview]Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
NCT02358031 (40) [back to overview]Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score
NCT02358031 (40) [back to overview]Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score
NCT02358031 (40) [back to overview]Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
NCT02358031 (40) [back to overview]Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants
NCT02358031 (40) [back to overview]Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20
NCT02358031 (40) [back to overview]Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants
NCT02358031 (40) [back to overview]Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1
NCT02358031 (40) [back to overview]Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20
NCT02364999 (9) [back to overview]Serum Concentration of Bevacizumab up to 1 Year
NCT02364999 (9) [back to overview]Number of Participants With Neutralizing Antibody (NAb)
NCT02364999 (9) [back to overview]Number of Participants With Treatment-Emergent Adverse Events
NCT02364999 (9) [back to overview]Number of Participants With Anti-Drug Antibody (ADA)
NCT02364999 (9) [back to overview]Progression Free Survival Rate at 55 Weeks
NCT02364999 (9) [back to overview]Objective Response Rate (ORR) by Week 19
NCT02364999 (9) [back to overview]Duration of Response (DOR)
NCT02364999 (9) [back to overview]Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)
NCT02364999 (9) [back to overview]Survival Rate at 55 Weeks
NCT02366143 (27) [back to overview]OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
NCT02366143 (27) [back to overview]OS in Arm A Versus Arm C by PD-L1 Subgroup
NCT02366143 (27) [back to overview]OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
NCT02366143 (27) [back to overview]Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B
NCT02366143 (27) [back to overview]Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B
NCT02366143 (27) [back to overview]Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C
NCT02366143 (27) [back to overview]Cmin of Bevacizumab in Arm B and Arm C
NCT02366143 (27) [back to overview]Cmax of Bevacizumab in Arm B and Arm C
NCT02366143 (27) [back to overview]Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
NCT02366143 (27) [back to overview]Percentage of Participants With Adverse Events
NCT02366143 (27) [back to overview]Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population
NCT02366143 (27) [back to overview]Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population
NCT02366143 (27) [back to overview]OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population
NCT02366143 (27) [back to overview]TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score
NCT02366143 (27) [back to overview]Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score
NCT02366143 (27) [back to overview]Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population
NCT02366143 (27) [back to overview]Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C
NCT02366143 (27) [back to overview]Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C
NCT02366143 (27) [back to overview]Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C
NCT02366143 (27) [back to overview]PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population
NCT02366143 (27) [back to overview]PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup
NCT02366143 (27) [back to overview]PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population
NCT02366143 (27) [back to overview]PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population
NCT02366143 (27) [back to overview]Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population
NCT02366143 (27) [back to overview]OS Rates at Years 1 and 2 in Arm B Versus Arm C
NCT02366143 (27) [back to overview]OS Rates at Years 1 and 2 in Arm A Versus Arm C
NCT02366143 (27) [back to overview]OS in Arm B Versus Arm C by PD-L1 Subgroup
NCT02367781 (19) [back to overview]OS as Determined by the Investigator Using Recist v1.1 in the ITT Population
NCT02367781 (19) [back to overview]Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 in ITT-WT Population, ITT Population, and PD-L1 Expression Population and PD-L1 Expression WT Population
NCT02367781 (19) [back to overview]Event Free Rate (%) at Year 1 and 2 in ITT-WT Population and ITT Population
NCT02367781 (19) [back to overview]Event Free Rate (%) at Year 1 and 2 in PD-L1 Expression Population and PD-L1 Expression WT Population
NCT02367781 (19) [back to overview]Maximum Observed Serum Concentration (Cmax) of Atezolizumab for Patients in Atezolizumab+Carboplatin+Nab-Paclitaxel Arm
NCT02367781 (19) [back to overview]Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT-WT Population
NCT02367781 (19) [back to overview]Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT Population
NCT02367781 (19) [back to overview]Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms in the ITT-WT Population
NCT02367781 (19) [back to overview]Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Atezolizumab+Carboplain+Nab-Paclitaxel
NCT02367781 (19) [back to overview]Percentage of Participants With Adverse Events
NCT02367781 (19) [back to overview]OS as Determined by the Investigator Using RECIST v1.1 in the PD-L1 Expression Population and PD-L1 Expression WT Population
NCT02367781 (19) [back to overview]Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population
NCT02367781 (19) [back to overview]Overall Survival (OS) in the ITT-WT Population
NCT02367781 (19) [back to overview]Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab
NCT02367781 (19) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale
NCT02367781 (19) [back to overview]PFS as Determined by the Investigator Using Recist v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population
NCT02367781 (19) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale
NCT02367781 (19) [back to overview]Plasma Concentrations of Carboplatin
NCT02367781 (19) [back to overview]Plasma Concentrations of Nab-Paclitaxel Reported as Total Paclitaxel
NCT02367794 (25) [back to overview]OS in the TC2/3 or IC2/3 Population
NCT02367794 (25) [back to overview]PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B)
NCT02367794 (25) [back to overview]Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population
NCT02367794 (25) [back to overview]Percentage of Participants With Adverse Events
NCT02367794 (25) [back to overview]Overall Survival (OS) in the ITT Population
NCT02367794 (25) [back to overview]Plasma Concentrations for Nab-Paclitaxel
NCT02367794 (25) [back to overview]OS in the in the Teff Population
NCT02367794 (25) [back to overview]Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab
NCT02367794 (25) [back to overview]PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population
NCT02367794 (25) [back to overview]Plasma Concentrations for Carboplatin
NCT02367794 (25) [back to overview]Plasma Concentrations for Paclitaxel
NCT02367794 (25) [back to overview]OS in the TC1/2/3 or IC1/2/3 Population
NCT02367794 (25) [back to overview]OS in the ITT Population (Arm A and Arm B)
NCT02367794 (25) [back to overview]Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population
NCT02367794 (25) [back to overview]Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population
NCT02367794 (25) [back to overview]TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population
NCT02367794 (25) [back to overview]Minimum Observed Serum Atezolizumab Concentration (Cmin)
NCT02367794 (25) [back to overview]Maximum Observed Serum Atezolizumab Concentration (Cmax)
NCT02367794 (25) [back to overview]Event Free Rate at 1 and 2 Years in the ITT Population
NCT02367794 (25) [back to overview]Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population
NCT02367794 (25) [back to overview]Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population
NCT02367794 (25) [back to overview]Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population
NCT02367794 (25) [back to overview]Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population
NCT02367794 (25) [back to overview]PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population
NCT02367794 (25) [back to overview]PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population
NCT02382406 (11) [back to overview]Phase I: Disease Assessment for Progression-Free Survival (PFS)
NCT02382406 (11) [back to overview]Phase I: Overall Survival (OS)
NCT02382406 (11) [back to overview]Phase II: Disease Assessment for Anti-Tumor Activity
NCT02382406 (11) [back to overview]Phase II: Disease Assessment for Progression-Free Survival (PFS)
NCT02382406 (11) [back to overview]Phase I: Disease Assessment for Anti-Tumor Activity
NCT02382406 (11) [back to overview]Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability
NCT02382406 (11) [back to overview]All Phases: Assessment of Association of PD-L1 Expression on PFS
NCT02382406 (11) [back to overview]Phase II: Overall Survival (OS)
NCT02382406 (11) [back to overview]Phase II: Objective Response Rate
NCT02382406 (11) [back to overview]Phase I: Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Recommended Phase II Dose
NCT02382406 (11) [back to overview]Phase I : Objective Response Rate
NCT02383966 (7) [back to overview]Progression-free Survival (PFS) Time, as Assessed by the Investigator
NCT02383966 (7) [back to overview]Duration of Response (DOR)
NCT02383966 (7) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Emergent Adverse Events Leading to Death and AEs Leading to Discontinuation
NCT02383966 (7) [back to overview]Best Overall Response Rate (ORR)
NCT02383966 (7) [back to overview]Disease Control Rate (DCR)
NCT02383966 (7) [back to overview]Overall Survival (OS) Time
NCT02383966 (7) [back to overview]Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC)
NCT02392507 (7) [back to overview]Overall Survival (OS)
NCT02392507 (7) [back to overview]Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])
NCT02392507 (7) [back to overview]PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin
NCT02392507 (7) [back to overview]Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin
NCT02392507 (7) [back to overview]Progression Free Survival (PFS)
NCT02392507 (7) [back to overview]Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])
NCT02392507 (7) [back to overview]Immunogenicity: Number of Participants Developing Anti-drug Antibodies to Necitumumab
NCT02409342 (24) [back to overview]OS in Participants With Blood Tumor Mutational Burden (bTMB)
NCT02409342 (24) [back to overview]OS in Participants With PD-L1 Expression
NCT02409342 (24) [back to overview]Overall Survival (OS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
NCT02409342 (24) [back to overview]Percentage of Participants Who Are Alive at 1 Year in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
NCT02409342 (24) [back to overview]Percentage of Participants Who Are Alive at 2 Years in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
NCT02409342 (24) [back to overview]Percentage of Participants With Anti-therapeutic Antibodies (ATAs)
NCT02409342 (24) [back to overview]Percentage of Participants With Objective Response (ORR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
NCT02409342 (24) [back to overview]Progression-free Survival (PFS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
NCT02409342 (24) [back to overview]Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Score as Assessed by the Symptoms in Lung Cancer (SILC) Scale Symptom Score in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]TTD as Assessed Using EORTC QLQ Supplementary Lung Cancer Module (EORTC QLQ-LC13) in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Duration of Response (DOR) in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Maximum Observed Serum Concentration (Cmax) of Atezolizumab
NCT02409342 (24) [back to overview]Overall Survival (OS) in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Percentage of Participants Who Are Alive at 1 Year in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Percentage of Participants Who Are Alive at 2 Years in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Percentage of Participants With at Least One Adverse Event
NCT02409342 (24) [back to overview]Percentage of Participants With Objective Response (ORR) in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Progression-free Survival (PFS) in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Change From Baseline in Patient-reported Lung Cancer Symptoms Score as Assessed by the SILC Scale Symptom Score in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Change From Baseline in Patient-reported Lung Cancer Symptoms Score as Assessed by the SILC Scale Symptom Score in the TC3 or IC3-WT Populations
NCT02409342 (24) [back to overview]Duration of Response (DOR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations
NCT02409342 (24) [back to overview]Investigator-Assessed PFS in Participants With bTMB According to RECIST v1.1
NCT02409342 (24) [back to overview]Investigator-Assessed PFS in Participants With PD-L1 Expression According to RECIST v1.1
NCT02409342 (24) [back to overview]Minimum Observed Serum Concentration (Cmin) of Atezolizumab
NCT02412371 (5) [back to overview]Overall Survival
NCT02412371 (5) [back to overview]Duration of Overall Response (DOR)
NCT02412371 (5) [back to overview]Number of Participants With Dose-limiting Toxicities (DLTs)
NCT02412371 (5) [back to overview]Objective Response Rate
NCT02412371 (5) [back to overview]Progression-free Survival
NCT02412670 (7) [back to overview]Event-free Survival
NCT02412670 (7) [back to overview]Proportion of Patients With Renal Insufficiency at Completion of Chemotherapy
NCT02412670 (7) [back to overview]Recurrence-free Survival
NCT02412670 (7) [back to overview]Proportion of Patients With Renal Insufficiency at Completion of Surgery
NCT02412670 (7) [back to overview]Bladder Cancer-free Survival
NCT02412670 (7) [back to overview]Complete Pathologic Response Rate
NCT02412670 (7) [back to overview]Cumulative Incidence of Cancer-specific Death at 24 Months
NCT02413320 (2) [back to overview]Number of Participants With Minimal Residual Disease
NCT02413320 (2) [back to overview]Number of Participants With Pathological Complete Response
NCT02419742 (5) [back to overview]Percentage of Participants With Adverse Events
NCT02419742 (5) [back to overview]Overall Survival (OS)
NCT02419742 (5) [back to overview]Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography
NCT02419742 (5) [back to overview]Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography
NCT02419742 (5) [back to overview]Disease Free Survival (DFS)
NCT02435680 (13) [back to overview]Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption
NCT02435680 (13) [back to overview]Serum C-terminal Telopeptide of Type I Collagen (CTX-I)
NCT02435680 (13) [back to overview]MCS110 Dose Intensity
NCT02435680 (13) [back to overview]Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)
NCT02435680 (13) [back to overview]Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response
NCT02435680 (13) [back to overview]Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment)
NCT02435680 (13) [back to overview]Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
NCT02435680 (13) [back to overview]Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau
NCT02435680 (13) [back to overview]Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax
NCT02435680 (13) [back to overview]AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)
NCT02435680 (13) [back to overview]Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.
NCT02435680 (13) [back to overview]Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels
NCT02435680 (13) [back to overview]Circulating Monocytes Cells in Blood
NCT02445391 (6) [back to overview]Proportion of Basal Subtype
NCT02445391 (6) [back to overview]3-year Recurrence-Free Survival (RFS) Rate in Basal-Subtype Patients
NCT02445391 (6) [back to overview]Health-related Quality of Life (HRQL) at 6-month Assessment
NCT02445391 (6) [back to overview]Health-related Quality of Life (HRQL) at 15-month Assessment
NCT02445391 (6) [back to overview]3-year Overall Survival (OS) Rate in Basal-Subtype Patients
NCT02445391 (6) [back to overview]3-year Invasive Disease-Free Survival (IDFS) Rate in Basal-Subtype Patients
NCT02446600 (4) [back to overview]Patient Reported Scores of Disease-related Symptoms as Measured by the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy Ovarian Symptom Index-18 Disease-Related Symptom-Physical
NCT02446600 (4) [back to overview]Frequency and Severity of Adverse Effects
NCT02446600 (4) [back to overview]Progression Free Survival Determined Using Response Evaluation Criteria in Solid Tumors Version 1.1 Criteria
NCT02446600 (4) [back to overview]Overall Survival
NCT02453282 (29) [back to overview]Serum Concentrations of Tremelimumab
NCT02453282 (29) [back to overview]Serum Concentrations of Durvalumab
NCT02453282 (29) [back to overview]Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
NCT02453282 (29) [back to overview]Number of Participants With ADA Response to Tremelimumab
NCT02453282 (29) [back to overview]Change From Baseline in Disease-Related Symptoms as Assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC QLQ) at 12 Months
NCT02453282 (29) [back to overview]Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab
NCT02453282 (29) [back to overview]Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population
NCT02453282 (29) [back to overview]Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy
NCT02453282 (29) [back to overview]PFS2; PD-L1 (TC >=1%) Analysis Set Population
NCT02453282 (29) [back to overview]PFS2; FAS Population
NCT02453282 (29) [back to overview]PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
NCT02453282 (29) [back to overview]PFS; PD-L1 (TC >=1%) Analysis Set Population
NCT02453282 (29) [back to overview]PFS; FAS Population
NCT02453282 (29) [back to overview]Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population
NCT02453282 (29) [back to overview]Percentage of Participants APF12; FAS Population
NCT02453282 (29) [back to overview]Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population
NCT02453282 (29) [back to overview]Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy
NCT02453282 (29) [back to overview]OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy
NCT02453282 (29) [back to overview]OS; PD-L1 (TC >=1%) Analysis Set Population
NCT02453282 (29) [back to overview]OS; FAS Population
NCT02453282 (29) [back to overview]ORR; PD-L1 (TC >=1%) Analysis Set Population
NCT02453282 (29) [back to overview]ORR; FAS Population
NCT02453282 (29) [back to overview]Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population
NCT02453282 (29) [back to overview]Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab
NCT02453282 (29) [back to overview]Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population
NCT02453282 (29) [back to overview]DoR; PD-L1 (TC >=1%) Analysis Set Population
NCT02453282 (29) [back to overview]DoR; FAS Population
NCT02453282 (29) [back to overview]Ctrough_ss of Tremelimumab
NCT02453282 (29) [back to overview]Cmax_ss of Tremelimumab
NCT02469116 (3) [back to overview]Adverse Events as Measured by Number of Events Experienced by All Participants
NCT02469116 (3) [back to overview]Efficacy of Regimen as Measured by CA-125 Response
NCT02469116 (3) [back to overview]Incidence of Grade 3-4 Neutropenia as Measured by CTCAE Version 3
NCT02470585 (6) [back to overview]Progression-Free Survival (PFS) in the Intention-to-treat Population
NCT02470585 (6) [back to overview]Change From Baseline in Disease Related Symptom (DRS) Score in the BRCA-mutation Population
NCT02470585 (6) [back to overview]Progression-Free Survival (PFS) in the BRCA-deficient Population
NCT02470585 (6) [back to overview]Change From Baseline in Disease Related Symptom (DRS) Score in the HRD Population
NCT02470585 (6) [back to overview]Change From Baseline in Disease Related Symptom (DRS) Score in the ITT Population
NCT02470585 (6) [back to overview]Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort
NCT02499770 (53) [back to overview]Time to First Major Adverse Hematologic Event (MAHE) in Part 1
NCT02499770 (53) [back to overview]Occurrence of Grade 3/4 Neutropenia in Part 1
NCT02499770 (53) [back to overview]Occurrence of G-CSF Administration in Part 2
NCT02499770 (53) [back to overview]Change From Baseline of Platelet Count at the End of Cycle 6, Part 1
NCT02499770 (53) [back to overview]Tmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Time of Maximum Observed Concentration (Tmax) of Trilaciclib in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Occurrence of RBC Transfusion in Part 2
NCT02499770 (53) [back to overview]Number of Participants With Dose Limiting Toxicities by Cohort in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Trilaciclib in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Incidence of Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Related AEs, Related SAEs, and AEs Leading to Study Drug Discontinuation in Part 1
NCT02499770 (53) [back to overview]Cmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Best Overall Tumor Response Based on Blinded Independent Central Review (BICR) Assessments in Part 1
NCT02499770 (53) [back to overview]Best Overall Tumor Response Based on BICR Assessments in Part 2
NCT02499770 (53) [back to overview]Best Overall Tumor Response Based on Assessments in Part 2
NCT02499770 (53) [back to overview]Best Overall Tumor Response Based on Assessments in Part 1
NCT02499770 (53) [back to overview]AUC0-inf of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Trilaciclib in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Nadir of Absolute Neutrophil Count in Cycle 1, Part 2
NCT02499770 (53) [back to overview]Time to First MAHE in Part 2
NCT02499770 (53) [back to overview]Progression Free Survival (PFS) Based on Assessments in Part 1
NCT02499770 (53) [back to overview]PFS Based on Assessments in Part 2
NCT02499770 (53) [back to overview]OS in Part 2
NCT02499770 (53) [back to overview]OS in Part 1
NCT02499770 (53) [back to overview]Occurrence of Severe (Grade 4) Neutropenia in Part 2
NCT02499770 (53) [back to overview]Occurrence of Severe (Grade 4) Neutropenia in Part 1
NCT02499770 (53) [back to overview]Change From Baseline of Platelet Count at the End of Cycle 6, Part 2
NCT02499770 (53) [back to overview]Occurrence of Red Blood Cell (RBC) Transfusion in Part 1
NCT02499770 (53) [back to overview]Occurrence of Pulmonary Infection SAE in Part 2
NCT02499770 (53) [back to overview]Occurrence of Pulmonary Infection SAE in Part 1
NCT02499770 (53) [back to overview]Occurrence of Platelet Transfusion in Part 2
NCT02499770 (53) [back to overview]Occurrence of Platelet Transfusion in Part 1
NCT02499770 (53) [back to overview]Occurrence of IV Antibiotic Administration in Part 2
NCT02499770 (53) [back to overview]Occurrence of IV Antibiotic Administration in Part 1
NCT02499770 (53) [back to overview]Occurrence of Febrile Neutropenia in Part 1
NCT02499770 (53) [back to overview]Duration of Grade 3/4 Neutropenia in Part 1
NCT02499770 (53) [back to overview]Duration of Grade 3/4 Neutropenia in Part 2
NCT02499770 (53) [back to overview]Occurrence of Febrile Neutropenia in Part 2
NCT02499770 (53) [back to overview]Duration of Severe (Grade 4) Neutropenia in Part 2
NCT02499770 (53) [back to overview]Occurrence of ESA Administration in Part 2
NCT02499770 (53) [back to overview]Change From Baseline of Hemoglobin at the End of Cycle 6, Part 1
NCT02499770 (53) [back to overview]Change From Baseline of Hemoglobin at the End of Cycle 6, Part 2
NCT02499770 (53) [back to overview]Occurrence of Infectious SAEs in Part 2
NCT02499770 (53) [back to overview]Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 1
NCT02499770 (53) [back to overview]Occurrence of Erythropoietin Stimulating Agent (ESA) Administration in Part 1
NCT02499770 (53) [back to overview]Nadir of Absolute Neutrophil Count in Cycle 1, Part 1
NCT02499770 (53) [back to overview]Occurrence of Dose Reduction in Part 2
NCT02499770 (53) [back to overview]Occurrence of Dose Reduction in Part 1
NCT02499770 (53) [back to overview]Duration of Severe (Grade 4) Neutropenia in Cycle 1 of Part 2
NCT02499770 (53) [back to overview]Duration of Severe (Grade 4) Neutropenia in Part 1
NCT02499770 (53) [back to overview]Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 2
NCT02499770 (53) [back to overview]Occurrence of Infectious SAEs in Part 1
NCT02499770 (53) [back to overview]Occurrence of Granulocyte-Colony Stimulating Factor (G-CSF) Administration in Part 1
NCT02499770 (53) [back to overview]Occurrence of Grade 3/4 Neutropenia in Part 2
NCT02516241 (40) [back to overview]Disease Control Rate (DCR) at 12 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
NCT02516241 (40) [back to overview]Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set
NCT02516241 (40) [back to overview]Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set
NCT02516241 (40) [back to overview]PFS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
NCT02516241 (40) [back to overview]Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients
NCT02516241 (40) [back to overview]Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Improvement in Fatigue and Deterioration in Pain Per FACT-BL, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Alive and Progression-free at 12 Months (APF12), Full Analysis Set
NCT02516241 (40) [back to overview]Alive and Progression-free at 12 Months (APF12), PD-L1-High Analysis Set
NCT02516241 (40) [back to overview]Alive and Progression-free at 12 Months (APF12), PD-L1-Low/Negative Analysis Set
NCT02516241 (40) [back to overview]Alive at 24 Months (OS24), Full Analysis Set
NCT02516241 (40) [back to overview]Alive at 24 Months (OS24), PD-L1-High Analysis Set
NCT02516241 (40) [back to overview]Alive at 24 Months (OS24), PD-L1-Low/Negative Analysis Set
NCT02516241 (40) [back to overview]Objective Response Rate (ORR), PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
NCT02516241 (40) [back to overview]Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]To Assess the Efficacy of Durvalumab Monotherapy Versus SoC in Terms of OS in PD-L1-High Analysis Set
NCT02516241 (40) [back to overview]To Assess the Efficacy of Durvalumab + Tremelimumab Combination Therapy Versus SoC in Terms of OS in Full Analysis Set
NCT02516241 (40) [back to overview]PFS2, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
NCT02516241 (40) [back to overview]PFS2, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
NCT02516241 (40) [back to overview]Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients
NCT02516241 (40) [back to overview]PFS2, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Objective Response Rate (ORR), PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
NCT02516241 (40) [back to overview]OS, Full Analysis Set - Durvalumab Monotherapy vs SoC
NCT02516241 (40) [back to overview]OS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC
NCT02516241 (40) [back to overview]OS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
NCT02516241 (40) [back to overview]PFS, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]PFS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
NCT02516241 (40) [back to overview]Objective Response Rate (ORR), Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Objective Response Rate (ORR) Based on BICR Assessment According to RECIST 1.1 - Responses Are Confirmed - Durvalumab Cisplatin Ineligible Population
NCT02516241 (40) [back to overview]Duration of Response (DoR), PD-L1-Low/Negative Analysis Set
NCT02516241 (40) [back to overview]Duration of Response (DoR), PD-L1-High Analysis Set
NCT02516241 (40) [back to overview]Duration of Response (DoR), Full Analysis Set
NCT02516241 (40) [back to overview]Disease Control Rate (DCR) at 12 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Disease Control Rate (DCR) at 6 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
NCT02516241 (40) [back to overview]Disease Control Rate (DCR) at 6 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC
NCT02516241 (40) [back to overview]Disease Control Rate (DCR) at 6 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC
NCT02516241 (40) [back to overview]Disease Control Rate (DCR) at 12 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy
NCT02530437 (3) [back to overview]Pathologic Complete Response Rate (Phase II)
NCT02530437 (3) [back to overview]Overall Survival
NCT02530437 (3) [back to overview]Relapse-free Survival
NCT02542293 (20) [back to overview]Serum Concentrations of Durvalumab
NCT02542293 (20) [back to overview]Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
NCT02542293 (20) [back to overview]Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab
NCT02542293 (20) [back to overview]OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set
NCT02542293 (20) [back to overview]Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set
NCT02542293 (20) [back to overview]Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
NCT02542293 (20) [back to overview]APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
NCT02542293 (20) [back to overview]DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
NCT02542293 (20) [back to overview]PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
NCT02542293 (20) [back to overview]Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
NCT02542293 (20) [back to overview]Number of Participants With ADA Response to Tremelimumab
NCT02542293 (20) [back to overview]Serum Concentrations of Tremelimumab
NCT02542293 (20) [back to overview]Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
NCT02542293 (20) [back to overview]ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets
NCT02542293 (20) [back to overview]OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets
NCT02542293 (20) [back to overview]OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets
NCT02542293 (20) [back to overview]OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets
NCT02542293 (20) [back to overview]OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
NCT02542293 (20) [back to overview]PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets
NCT02542293 (20) [back to overview]Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets
NCT02547987 (1) [back to overview]Pathologic Complete Response
NCT02549209 (2) [back to overview]Proportion of Subjects Who Experience ≥ Grade 3 Toxicity According Per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Criteria
NCT02549209 (2) [back to overview]Objective Response Rates (ORR)
NCT02551159 (9) [back to overview]Duration of Response (DoR) in the All-comers (Full Analysis Set)
NCT02551159 (9) [back to overview]Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)
NCT02551159 (9) [back to overview]Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)
NCT02551159 (9) [back to overview]Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup
NCT02551159 (9) [back to overview]Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)
NCT02551159 (9) [back to overview]Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup
NCT02551159 (9) [back to overview]Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup
NCT02551159 (9) [back to overview]Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup
NCT02551159 (9) [back to overview]Progression Free Survival (PFS) in the All-comers (Full Analysis Set)
NCT02561832 (1) [back to overview]Part A: Number of Subjects Reporting Adverse Events (AEs)
NCT02565901 (2) [back to overview]Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phases I and II)
NCT02565901 (2) [back to overview]Percentage of Patients With Reduction in Prostate Specific Antigen According to the Prostate Cancer Working Group 2 (PCWG2) Criteria (Phases I and II)
NCT02567799 (21) [back to overview]Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan
NCT02567799 (21) [back to overview]Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy
NCT02567799 (21) [back to overview]DLCO as Measured by Pulmonary Function Test (PFT)
NCT02567799 (21) [back to overview]Extent of Esophagitis by Patient Reported Swallowing Diary
NCT02567799 (21) [back to overview]FVC as Measured by Pulmonary Function Test (PFT)
NCT02567799 (21) [back to overview]Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300
NCT02567799 (21) [back to overview]Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300
NCT02567799 (21) [back to overview]FEV1 as Measured by Pulmonary Function Test (PFT)
NCT02567799 (21) [back to overview]Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin
NCT02567799 (21) [back to overview]Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300
NCT02567799 (21) [back to overview]Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300
NCT02567799 (21) [back to overview]Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire.
NCT02567799 (21) [back to overview]Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1)
NCT02567799 (21) [back to overview]Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) Patient Reported Outcome Questionnaire.
NCT02567799 (21) [back to overview]Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy
NCT02567799 (21) [back to overview]Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin
NCT02567799 (21) [back to overview]Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin
NCT02567799 (21) [back to overview]Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300
NCT02567799 (21) [back to overview]Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300
NCT02567799 (21) [back to overview]Number of Participants With Adverse Events Throughout the Study
NCT02567799 (21) [back to overview]Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT)
NCT02574078 (7) [back to overview]Progression-Free Survival (PFS), Groups A-D Only
NCT02574078 (7) [back to overview]Progression-Free Survival (PFS), Group E Only
NCT02574078 (7) [back to overview]Overall Survival (OS), Groups A-C Only
NCT02574078 (7) [back to overview]Objective Response Rate (ORR), Groups A-E
NCT02574078 (7) [back to overview]Duration of Response (DOR), Groups A-D Only
NCT02574078 (7) [back to overview]Percentage of Participants With Treatment-related Adverse Events (AEs) Leading to Both Study Drugs Discontinuation, Group E Only
NCT02574078 (7) [back to overview]Overall Survival (OS), Group D Only
NCT02576574 (32) [back to overview]Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease
NCT02576574 (32) [back to overview]Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)
NCT02576574 (32) [back to overview]Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)
NCT02576574 (32) [back to overview]Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High PD-L1+ Full Analysis Set
NCT02576574 (32) [back to overview]Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High PD-L1+ Modified Full Analysis Set
NCT02576574 (32) [back to overview]Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in Moderate and High PD-L1+ Full Analysis Set
NCT02576574 (32) [back to overview]Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)
NCT02576574 (32) [back to overview]Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)
NCT02576574 (32) [back to overview]Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease
NCT02576574 (32) [back to overview]Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Weight Increase/Decrease
NCT02576574 (32) [back to overview]Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Electrocardiogram (ECG) Parameters
NCT02576574 (32) [back to overview]Number of Participants With Shift From Baseline to Greater Than or Equal to (>=) Grade 3 in Laboratory Parameter Values Based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03
NCT02576574 (32) [back to overview]Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in Moderate and High PD-L1+ Modified Full Analysis Set
NCT02576574 (32) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)
NCT02576574 (32) [back to overview]Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ HRQoL Analysis Set
NCT02576574 (32) [back to overview]Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set
NCT02576574 (32) [back to overview]Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) in High PD-L1+ Health-related Quality of Life (HRQoL) Analysis Set at End of Treatment
NCT02576574 (32) [back to overview]Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set
NCT02576574 (32) [back to overview]Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)
NCT02576574 (32) [back to overview]Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)
NCT02576574 (32) [back to overview]Overall Survival (OS) in Full Analysis Set (FAS)
NCT02576574 (32) [back to overview]Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)
NCT02576574 (32) [back to overview]Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1) + Modified Full Analysis Set (mFAS)
NCT02576574 (32) [back to overview]Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)
NCT02576574 (32) [back to overview]Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set
NCT02576574 (32) [back to overview]Overall Survival (OS) in Modified Full Analysis Set (mFAS)
NCT02576574 (32) [back to overview]Number of Participants With At Least One Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab
NCT02576574 (32) [back to overview]Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score
NCT02576574 (32) [back to overview]Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Body Temperature Increase
NCT02576574 (32) [back to overview]Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)
NCT02576574 (32) [back to overview]Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ HRQoL Analysis Set
NCT02576574 (32) [back to overview]Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Heart Rate Increase/Decrease
NCT02578641 (2) [back to overview]Progression-free Survival (PFS) of Subjects With Advanced Nasopharyngeal Carcinoma.
NCT02578641 (2) [back to overview]Overall Survival (OS) of Subjects With Advanced Nasopharyngeal Carcinoma.
NCT02578680 (6) [back to overview]Overall Survival (OS)
NCT02578680 (6) [back to overview]Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
NCT02578680 (6) [back to overview]Number of Participants Who Discontinued Any Study Drug Due to an AE
NCT02578680 (6) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT02578680 (6) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging
NCT02578680 (6) [back to overview]Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
NCT02590003 (7) [back to overview]Symptom Assessment (Measured by FACT-L Symptom Assessment Scale)
NCT02590003 (7) [back to overview]Symptom Assessment (Measured by FACT-L Symptom Assessment Scale)
NCT02590003 (7) [back to overview]Treatment Failure-free Survival
NCT02590003 (7) [back to overview]Grade 3-5 Adverse Events
NCT02590003 (7) [back to overview]Overall Response Rate
NCT02590003 (7) [back to overview]Overall Survival
NCT02590003 (7) [back to overview]Progression-free Survival
NCT02591615 (3) [back to overview]Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
NCT02591615 (3) [back to overview]Overall Response Rate (ORR) Per RECIST 1.1
NCT02591615 (3) [back to overview]Compare Progression-Free Survival (PFS) Per RECIST 1.1
NCT02592876 (10) [back to overview]Complete Remission Rate Per Independent Review Facility
NCT02592876 (10) [back to overview]Progression-free Survival (PFS)
NCT02592876 (10) [back to overview]Duration of Complete Response (CR)
NCT02592876 (10) [back to overview]Duration of Objective Response (OR)
NCT02592876 (10) [back to overview]Objective Response Rate (ORR)
NCT02592876 (10) [back to overview]Overall Survival (OS)
NCT02592876 (10) [back to overview]Number of Participants With Adverse Events (AEs)
NCT02592876 (10) [back to overview]Number of Participants With Laboratory Abnormalities
NCT02592876 (10) [back to overview]Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization
NCT02592876 (10) [back to overview]Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)
NCT02621398 (1) [back to overview]Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of the Combination of Pembrolizumab With Paclitaxel, Carboplatin and Radiation Therapy According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
NCT02622074 (13) [back to overview]Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 (No Invasive Residual in Breast or Nodes; Noninvasive Breast Residuals Allowed)
NCT02622074 (13) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: First Combination Regimen
NCT02622074 (13) [back to overview]Event-Free Survival (EFS) Rate at Month 6
NCT02622074 (13) [back to overview]Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
NCT02622074 (13) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT02622074 (13) [back to overview]Number of Participants With Dose Limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
NCT02622074 (13) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: Second Combination Regimen
NCT02622074 (13) [back to overview]Overall Survival (OS) Rate at Month 12
NCT02622074 (13) [back to overview]Event-Free Survival (EFS) Rate at Month 12
NCT02622074 (13) [back to overview]Event-Free Survival (EFS) Rate at Month 24
NCT02622074 (13) [back to overview]Overall Survival (OS) Rate at Month 6
NCT02622074 (13) [back to overview]Overall Survival (OS) Rate at Month 24
NCT02622074 (13) [back to overview]Pathological Complete Response (pCR) Rate Using the Definition of ypT0 ypN0 (No Invasive or Noninvasive Residual in Breast or Nodes)
NCT02633800 (1) [back to overview]Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population
NCT02657434 (18) [back to overview]Plasma Concentrations for Cisplatin in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
NCT02657434 (18) [back to overview]Plasma Concentrations for Pemetrexed in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
NCT02657434 (18) [back to overview]Plasma Concentrations for Carboplatin in Arm A(Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)
NCT02657434 (18) [back to overview]Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1
NCT02657434 (18) [back to overview]Maximum Observed Serum Atezolizumab Concentration (Cmax)
NCT02657434 (18) [back to overview]Overall Survival (OS)
NCT02657434 (18) [back to overview]Overall Survival Rate at Year 1
NCT02657434 (18) [back to overview]Overall Survival Rate Year 2
NCT02657434 (18) [back to overview]Progression Free Survival (PFS) as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
NCT02657434 (18) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score
NCT02657434 (18) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score
NCT02657434 (18) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score
NCT02657434 (18) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score
NCT02657434 (18) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score
NCT02657434 (18) [back to overview]Change From Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score
NCT02657434 (18) [back to overview]Minimum Observed Serum Atezolizumab Concentration (Cmin)
NCT02657434 (18) [back to overview]Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1
NCT02657434 (18) [back to overview]Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) of Atezolizumab
NCT02659059 (17) [back to overview]Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2
NCT02659059 (17) [back to overview]Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1
NCT02659059 (17) [back to overview]Overall Survival (OS) - Part 1
NCT02659059 (17) [back to overview]Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1
NCT02659059 (17) [back to overview]Number of Participants With Adverse Events (AEs) - Part 2
NCT02659059 (17) [back to overview]Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1
NCT02659059 (17) [back to overview]Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1
NCT02659059 (17) [back to overview]Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2
NCT02659059 (17) [back to overview]Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2
NCT02659059 (17) [back to overview]Progression Free Survival (PFS) - Part 2
NCT02659059 (17) [back to overview]Overall Survival (OS) by PD-L1 Expression Levels - Part 1
NCT02659059 (17) [back to overview]Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1
NCT02659059 (17) [back to overview]Progression Free Survival (PFS) - Part 1
NCT02659059 (17) [back to overview]Overall Survival (OS) - Part 2
NCT02659059 (17) [back to overview]Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1
NCT02659059 (17) [back to overview]Objective Response Rate (ORR) - Part 1
NCT02659059 (17) [back to overview]Objective Response Rate (ORR) - Part 2
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth
NCT02684058 (53) [back to overview]LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score
NCT02684058 (53) [back to overview]LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score
NCT02684058 (53) [back to overview]LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score
NCT02684058 (53) [back to overview]T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
NCT02684058 (53) [back to overview]Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed
NCT02684058 (53) [back to overview]AUClast for Trametinib
NCT02684058 (53) [back to overview]AUCtau for Trametinib
NCT02684058 (53) [back to overview]Cmax for Trametinib
NCT02684058 (53) [back to overview]Ctrough for Trametinib
NCT02684058 (53) [back to overview]HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)
NCT02684058 (53) [back to overview]HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
NCT02684058 (53) [back to overview]HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: 2-year OS Estimate
NCT02684058 (53) [back to overview]LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)
NCT02684058 (53) [back to overview]LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth
NCT02684058 (53) [back to overview]HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water
NCT02684058 (53) [back to overview]LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria
NCT02684058 (53) [back to overview]T1/2 for Trametinib
NCT02684058 (53) [back to overview]Tmax for Trametinib
NCT02684058 (53) [back to overview]All-collected Deaths
NCT02684058 (53) [back to overview]All-collected Deaths
NCT02684058 (53) [back to overview]AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
NCT02684058 (53) [back to overview]AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
NCT02684058 (53) [back to overview]Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
NCT02684058 (53) [back to overview]Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)
NCT02684058 (53) [back to overview]HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]HGG Cohort: ORR by Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: ORR by Investigator Assessment Using RANO Criteria
NCT02684058 (53) [back to overview]LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score
NCT02684058 (53) [back to overview]LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score
NCT02684058 (53) [back to overview]LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score
NCT02703272 (37) [back to overview]Part 2: Overall Survival
NCT02703272 (37) [back to overview]Part 2: Percentage of Participants With EFS at 2 Years
NCT02703272 (37) [back to overview]Part 2: Percentage of Participants Who Achieved Partial Response (PR)
NCT02703272 (37) [back to overview]Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Percentage of Participants Who Achieved Complete Response (CR)
NCT02703272 (37) [back to overview]Part 1 and Part 2: Overall Response Rate (ORR)
NCT02703272 (37) [back to overview]Part 2: Number of Participants With c-MYC Gene Rearrangement
NCT02703272 (37) [back to overview]Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation
NCT02703272 (37) [back to overview]Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups
NCT02703272 (37) [back to overview]Part 2: Duration of Response
NCT02703272 (37) [back to overview]Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability
NCT02703272 (37) [back to overview]Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline
NCT02703272 (37) [back to overview]Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy
NCT02703272 (37) [back to overview]Part 2: Tumor Volume Reduction Rate at Day 14
NCT02703272 (37) [back to overview]Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations
NCT02703272 (37) [back to overview]Part 2: Time to Response
NCT02703272 (37) [back to overview]Part 2: Percentage of Participants With EFS at 3 Years
NCT02703272 (37) [back to overview]Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability
NCT02703272 (37) [back to overview]Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib
NCT02703272 (37) [back to overview]Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib
NCT02709512 (4) [back to overview]Overall Survival
NCT02709512 (4) [back to overview]Progression Free Survival
NCT02709512 (4) [back to overview]Response Rate
NCT02709512 (4) [back to overview]Overall Survival Phase 3 Interim Analysis
NCT02710396 (4) [back to overview]Progression Free Survival (PFS)
NCT02710396 (4) [back to overview]Number of Subjects With NSCLC Who Achieved DCB
NCT02710396 (4) [back to overview]Objective Response Rate (ORR)
NCT02710396 (4) [back to overview]Overall Survival (OS)
NCT02716038 (1) [back to overview]Number of Subjects With Major Pathologic Response (MPR)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Carboplatin (Total and Free)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Carboplatin (Total and Free)
NCT02718417 (35) [back to overview]Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment
NCT02718417 (35) [back to overview]Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment
NCT02718417 (35) [back to overview]Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment
NCT02718417 (35) [back to overview]Functional Assessment of Ovarian Symptom Index- 18 (FOSI-18) Score
NCT02718417 (35) [back to overview]Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Carboplatin (Total and Free)
NCT02718417 (35) [back to overview]Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
NCT02718417 (35) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
NCT02718417 (35) [back to overview]Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status
NCT02718417 (35) [back to overview]Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03
NCT02718417 (35) [back to overview]Number of Participants With Electrocardiogram (ECG) Abnormalities
NCT02718417 (35) [back to overview]Maintenance Progression-Free Survival (PFS) as Assessed by Investigator
NCT02718417 (35) [back to overview]Maintenance Phase: Predose Plasma Concentration (Ctrough) of Avelumab
NCT02718417 (35) [back to overview]Maintenance Phase: Maximum Plasma Concentration (Cmax) of Avelumab
NCT02718417 (35) [back to overview]Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status
NCT02718417 (35) [back to overview]Duration of Response (DOR) as Assessed by Investigator
NCT02718417 (35) [back to overview]Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Predose Plasma Concentration (Ctrough) of Avelumab When Given With Paclitaxel and Carboplatin
NCT02718417 (35) [back to overview]Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once Every Three Weeks [Q3W] Regimen)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once a Week [QW] Regimen)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Avelumab When Given With Paclitaxel and Carboplatin
NCT02718417 (35) [back to overview]Number of Participants With Positive Tumor-Infiltrating Cluster of Differentiation 8 (CD8+) T Lymphocytes Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)
NCT02718417 (35) [back to overview]Overall Survival
NCT02718417 (35) [back to overview]Maintenance Progression-Free Survival as Assessed by Blinded Independent Central Review (BICR)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (QW Regimen)
NCT02718417 (35) [back to overview]Percentage of Participants With Objective Response as Assessed by Investigator
NCT02718417 (35) [back to overview]Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (Q3W Regimen)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (QW Regimen)
NCT02718417 (35) [back to overview]Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (Q3W Regimen)
NCT02718417 (35) [back to overview]Percentage of Participants With Pathological Complete Response (pCR)
NCT02718417 (35) [back to overview]Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)
NCT02718417 (35) [back to overview]Progression-Free Survival (PFS) as Assessed by Investigator
NCT02718417 (35) [back to overview]Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment
NCT02730546 (1) [back to overview]Pathological Complete Response (PathCR) Rate
NCT02741570 (8) [back to overview]Overall Survival (OS) in All Randomized Participants
NCT02741570 (8) [back to overview]Overall Survival (OS) in All Randomized Participants - Extended Collection
NCT02741570 (8) [back to overview]Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20 - Extended Collection
NCT02741570 (8) [back to overview]Duration of Objective Response (DOR)
NCT02741570 (8) [back to overview]Objective Response Rate (ORR)
NCT02741570 (8) [back to overview]Progression Free Survival (PFS)
NCT02741570 (8) [back to overview]Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20
NCT02741570 (8) [back to overview]Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1
NCT02744898 (3) [back to overview]Objective Response Rate (ORR) as Measured by RECIST 1.1 at Month 24
NCT02744898 (3) [back to overview]Progression-Free Survival (PFS) at Month 24
NCT02744898 (3) [back to overview]Tolerability Measured Completion of Dose Regimen
NCT02748889 (1) [back to overview]Progression Free Survival (PFS) With Carboplatin, Etoposide and MPDL3280A Compared to Chemotherapy Alone According to RECIST v1.1
NCT02756013 (2) [back to overview]Relative Dose Intensity as Measured by Mean Percent of Intended Cycles Completed
NCT02756013 (2) [back to overview]Number of Participants With Progression-free Survival (PFS)
NCT02763579 (13) [back to overview]Plasma Concentration of Carboplatin in the Global Population
NCT02763579 (13) [back to overview]Percentage of Participants With at Least One Adverse Event in the Global Population
NCT02763579 (13) [back to overview]PFS Rate at 6 Months and at 1 Year in Global Population
NCT02763579 (13) [back to overview]Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population
NCT02763579 (13) [back to overview]Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
NCT02763579 (13) [back to overview]Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
NCT02763579 (13) [back to overview]Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population
NCT02763579 (13) [back to overview]Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population
NCT02763579 (13) [back to overview]Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population
NCT02763579 (13) [back to overview]OS Rate at 1 Year and 2 Years in the Global Population
NCT02763579 (13) [back to overview]Plasma Concentration of Etoposide in the Global Population
NCT02763579 (13) [back to overview]Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population
NCT02763579 (13) [back to overview]Duration of Overall Survival (OS) in the Global Population
NCT02766582 (2) [back to overview]Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy.
NCT02766582 (2) [back to overview]Progression Free Survival (PFS) of Combination Platinum Based Therapy With Anti-Programmed Death (PD)-1 Therapy Followed by Maintenance Anti-PD-1 Therapy in Patients With Epithelial Ovarian Cancer (EOC).
NCT02775435 (6) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT02775435 (6) [back to overview]Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT02775435 (6) [back to overview]Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT02775435 (6) [back to overview]Overall Survival (OS)
NCT02775435 (6) [back to overview]Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
NCT02775435 (6) [back to overview]Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT02784288 (6) [back to overview]Median Change in Quality of Life (QOL) From Baseline to 12 Months Post Treatment
NCT02784288 (6) [back to overview]Median Change in Quality of Life (QOL) From Baseline to 24 Months Post Treatment
NCT02784288 (6) [back to overview]Progression Free Survival (PFS)
NCT02784288 (6) [back to overview]Disease Specific Survival (DSS)
NCT02784288 (6) [back to overview]Impact of Neck Dissection on Shoulder Function Using the Neck Dissection Impairment Index
NCT02784288 (6) [back to overview]Overall Survival (OS)
NCT02789657 (2) [back to overview]Percent of Patients Who Achieve a pCR
NCT02789657 (2) [back to overview]Number of of Patients Who Develop Major Toxicities as Defined in Protocol.
NCT02807636 (19) [back to overview]Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]PFS Event Free Rate
NCT02807636 (19) [back to overview]Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)
NCT02807636 (19) [back to overview]Minimum Atezolizumab Serum Concentration
NCT02807636 (19) [back to overview]Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm
NCT02807636 (19) [back to overview]Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm
NCT02807636 (19) [back to overview]Maximum Atezolizumab Serum Concentration
NCT02807636 (19) [back to overview]IRF-PFS
NCT02807636 (19) [back to overview]Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02807636 (19) [back to overview]Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm
NCT02810457 (8) [back to overview]Overall Survival (OS)
NCT02810457 (8) [back to overview]Duration Of Response (DOR)
NCT02810457 (8) [back to overview]Serum Trough Concentration (Ctrough)
NCT02810457 (8) [back to overview]Proportion of Patients Developing Anti-drug Antibodies (ADAs)
NCT02810457 (8) [back to overview]ORR at Week 19
NCT02810457 (8) [back to overview]Overall Response Rate (ORR) Assessed as the Proportion of Patients With a Best Overall Response (BOR) of Either Complete Response (CR) or Partial Response (PR)
NCT02810457 (8) [back to overview]Progression-free Survival (PFS)
NCT02810457 (8) [back to overview]Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED
NCT02819518 (25) [back to overview]Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors
NCT02819518 (25) [back to overview]Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors
NCT02819518 (25) [back to overview]Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors
NCT02819518 (25) [back to overview]Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors
NCT02819518 (25) [back to overview]Part 2: Overall Survival (OS) - All Participants
NCT02819518 (25) [back to overview]Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants
NCT02819518 (25) [back to overview]Part 2: Percentage of Participants Who Experienced an AE- All Participants
NCT02819518 (25) [back to overview]Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors
NCT02819518 (25) [back to overview]Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors
NCT02819518 (25) [back to overview]Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors
NCT02819518 (25) [back to overview]Part 2: Progression-Free Survival (PFS) - All Participants
NCT02819518 (25) [back to overview]Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants
NCT02819518 (25) [back to overview]Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants
NCT02819518 (25) [back to overview]Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors
NCT02819518 (25) [back to overview]Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants
NCT02819518 (25) [back to overview]Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants
NCT02819518 (25) [back to overview]Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors
NCT02819518 (25) [back to overview]Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors
NCT02819518 (25) [back to overview]Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors
NCT02819518 (25) [back to overview]Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors
NCT02819518 (25) [back to overview]Part 2: Disease Control Rate (DCR) - All Participants
NCT02819518 (25) [back to overview]Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors
NCT02819518 (25) [back to overview]Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors
NCT02819518 (25) [back to overview]Part 2: Duration of Response (DOR) - All Participants
NCT02819518 (25) [back to overview]Part 2: Objective Response Rate (ORR) - All Participants
NCT02834975 (3) [back to overview]Pathologic Objective Response Rate (pORR) in Participants Receiving Protocol Therapy
NCT02834975 (3) [back to overview]Number of Participants Experiencing Treatment-related Toxicity
NCT02834975 (3) [back to overview]Progression-Free Survival (PFS)
NCT02853305 (20) [back to overview]Pembro Combo vs Chemo: Change From Baseline to Week 18 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
NCT02853305 (20) [back to overview]PFS Using RECIST 1.1 as Assessed by BICR at 6 Months
NCT02853305 (20) [back to overview]PFS Using RECIST 1.1 as Assessed by BICR at 18 Months
NCT02853305 (20) [back to overview]PFS Using RECIST 1.1 as Assessed by BICR at 12 Months
NCT02853305 (20) [back to overview]Pembro vs Chemo: TTD in the EORTC-QLQ-C30 GHS/QoL (Items 29 and 30) Combined Score
NCT02853305 (20) [back to overview]Pembro vs Chemo: OS in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10%
NCT02853305 (20) [back to overview]Pembro vs Chemo: OS
NCT02853305 (20) [back to overview]Pembro vs Chemo: ORR Using RECIST 1.1 as Assessed by BICR
NCT02853305 (20) [back to overview]Pembro vs Chemo: DOR Using RECIST 1.1 as Assessed by BICR
NCT02853305 (20) [back to overview]Pembro Combo vs Chemo: Progression-free Survival (PFS) Using Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
NCT02853305 (20) [back to overview]Pembro Combo vs Chemo: Time to Deterioration (TTD) in the EORTC-QLQ-C30 GHS/QoL (Items 29 and 30) Combined Score
NCT02853305 (20) [back to overview]Pembro vs Chemo: Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score
NCT02853305 (20) [back to overview]Pembro vs Chemo: PFS Using RECIST 1.1 as Assessed by BICR
NCT02853305 (20) [back to overview]Pembro Combo vs Chemo: Overall Survival (OS)
NCT02853305 (20) [back to overview]Pembro vs Chemo: DCR Using RECIST 1.1 as Assessed by BICR
NCT02853305 (20) [back to overview]Number of Participants Who Discontinue Study Drug Due to an AE
NCT02853305 (20) [back to overview]Pembro Combo vs Chemo: Objective Response Rate (ORR) Using RECIST 1.1 as Assessed by BICR
NCT02853305 (20) [back to overview]Pembro Combo vs Chemo: Duration of Response (DOR) Using RECIST 1.1 as Assessed by BICR
NCT02853305 (20) [back to overview]Pembro Combo vs Chemo: Disease Control Rate (DCR) Using RECIST 1.1 as Assessed by BICR
NCT02853305 (20) [back to overview]Number of Participants Who Experience an Adverse Event (AE)
NCT02855944 (12) [back to overview]Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)
NCT02855944 (12) [back to overview]Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)
NCT02855944 (12) [back to overview]Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)
NCT02855944 (12) [back to overview]Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)
NCT02855944 (12) [back to overview]Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)
NCT02855944 (12) [back to overview]Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)
NCT02855944 (12) [back to overview]Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population)
NCT02855944 (12) [back to overview]Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population)
NCT02855944 (12) [back to overview]Overall Survival (Efficacy Population)
NCT02855944 (12) [back to overview]Overall Survival (ITT Population)
NCT02855944 (12) [back to overview]Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)
NCT02855944 (12) [back to overview]Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)
NCT02862457 (17) [back to overview]Maximum Concentration (Cmax) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Maximum Concentration (Cmax) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Terminal Half-Life (t1/2) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Terminal Half-Life (t1/2) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Number of Participants Who Discontinued Study Treatment Due to An Adverse Event (AE)
NCT02862457 (17) [back to overview]Time to Maximum Concentration (Tmax) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Time to Maximum Concentration (Tmax) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Trough Concentration (Ctrough) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)
NCT02862457 (17) [back to overview]Trough Concentration (Ctrough) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab in Part A Cycles 1, 2, 4, 6, and 8
NCT02862457 (17) [back to overview]Trough Concentration (Ctrough) of Pembrolizumab in Part B Cycles 1, 2, 4, 6, and 8
NCT02862457 (17) [back to overview]Area Under the Concentration-Time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Area Under the Concentration-Time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) of Epacadostat in Part A
NCT02862457 (17) [back to overview]Number of Participants Who Experienced At Least One Adverse Event (AE)
NCT02862457 (17) [back to overview]Maximum Concentration (Cmax) of Pembrolizumab in Part B Cycle 1
NCT02862457 (17) [back to overview]Maximum Concentration (Cmax) of Pembrolizumab in Part A Cycle 1
NCT02864251 (6) [back to overview]Objective Response Rate (ORR) by Blinded Independent Centralized Review (BICR)
NCT02864251 (6) [back to overview]Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR)
NCT02864251 (6) [back to overview]Overall Survival (OS)
NCT02864251 (6) [back to overview]12 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)
NCT02864251 (6) [back to overview]9 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)
NCT02864251 (6) [back to overview]Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)
NCT02899299 (7) [back to overview]Overall Survival (OS) According to PD-L1 Expression Level
NCT02899299 (7) [back to overview]Objective Response Rate (ORR) According to PD-L1 Expression Level
NCT02899299 (7) [back to overview]Overall Survival (OS)
NCT02899299 (7) [back to overview]Disease Control Rate (DCR)
NCT02899299 (7) [back to overview]Objective Response Rate (ORR)
NCT02899299 (7) [back to overview]Progression Free Survival (PFS) According to PD-L1 Expression Level
NCT02899299 (7) [back to overview]Progression Free Survival (PFS)
NCT02937818 (18) [back to overview]Apparent Clearance of Drug at Steady State at Steady State (CLss/F)
NCT02937818 (18) [back to overview]Time to Response (TTR)
NCT02937818 (18) [back to overview]Serum Concentrations of Durvalumab and Tremelimumab
NCT02937818 (18) [back to overview]Plasma Concentrations of Adavosertib and Carboplatin
NCT02937818 (18) [back to overview]Area Under the Concentration-time Curve at Steady State (AUCss)
NCT02937818 (18) [back to overview]Duration of Response (DoR)
NCT02937818 (18) [back to overview]Maximum Concentration (Cmax)
NCT02937818 (18) [back to overview]Maximum Concentration at Steady State (Cmax,ss)
NCT02937818 (18) [back to overview]Minimum Concentration at Steady State (Cmin,ss)
NCT02937818 (18) [back to overview]Number of Participants With Overall Response
NCT02937818 (18) [back to overview]Progression Free Survival (PFS)
NCT02937818 (18) [back to overview]Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
NCT02937818 (18) [back to overview]Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t)
NCT02937818 (18) [back to overview]Time to Maximum Concentration (Tmax)
NCT02937818 (18) [back to overview]Time to Maximum Concentration at Steady State (Tmax,ss)
NCT02937818 (18) [back to overview]Partial Area Under the Concentration-time Curve (AUC0-6)
NCT02937818 (18) [back to overview]Overall Survival (OS)
NCT02937818 (18) [back to overview]Percentage of Participants With Disease Control at 12 Weeks
NCT02941523 (4) [back to overview]Objective Response Rate (ORR) at Cycle 3 and at Cycle 6 of Combination Therapy
NCT02941523 (4) [back to overview]Overall Clinical Response Rate at Cycle 3 and at Cycle 6 of Combination Therapy
NCT02941523 (4) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events (SAEs) Related to NOX66.
NCT02941523 (4) [back to overview]Number of Participants Who Experience Dose Limiting Toxicity (DLT) During NOX66 Monotherapy and During NOX66 Combination With Carboplatin
NCT02954172 (3) [back to overview]Objective Response Rate
NCT02954172 (3) [back to overview]Overall Survival Time
NCT02954172 (3) [back to overview]Progression-free Survival
NCT02957968 (7) [back to overview]Evaluation of Expression of Protein Programmed Death-Ligand 1 (PD-L1) Within Tumor, Stroma, and Infiltrating Immune Cells Combined, at Baseline and Following Immunotherapy.
NCT02957968 (7) [back to overview]Number of Adverse Events (AEs) Reported During and After Immune Treatment (ie, Decitabine and Pembrolizumab)
NCT02957968 (7) [back to overview]Number of Patients Meeting Criteria for Lymphocyte-predominant Breast Cancer (LPBC) Following Treatment With Decitabine and Pembrolizumab
NCT02957968 (7) [back to overview]Number of Patients With Pathologic Complete Response (pCR) in the Breast and Post-therapy Lymph Nodes.
NCT02957968 (7) [back to overview]The Percentage of Increase in Tumor and Stroma With Infiltrating Lymphocytes (TIL) From Baseline Pre-treatment Biopsy to Post-immunotherapy Biopsy Following Administration of Decitabine Followed by Pembrolizumab.
NCT02957968 (7) [back to overview]Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline.
NCT02957968 (7) [back to overview]Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline.
NCT02978716 (28) [back to overview]Terminal Elimination Half-Life (t1/2) of Free Carboplatin
NCT02978716 (28) [back to overview]Cumulative Dose of Gemcitabine
NCT02978716 (28) [back to overview]Cumulative Dose of Carboplatin
NCT02978716 (28) [back to overview]Dose Modifications - Number of Participants With Skipped Doses
NCT02978716 (28) [back to overview]Clearance (CL) of of Free Carboplatin
NCT02978716 (28) [back to overview]Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib
NCT02978716 (28) [back to overview]Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine
NCT02978716 (28) [back to overview]Overall Survival (OS)
NCT02978716 (28) [back to overview]Number of Participants With Grade 3 or 4 Thrombocytopenia
NCT02978716 (28) [back to overview]Number of Participants With Febrile Neutropenia (FN)
NCT02978716 (28) [back to overview]Number of Cycles Participants Received Treatment in Each Treatment Arm
NCT02978716 (28) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Trilaciclib
NCT02978716 (28) [back to overview]Maximum Observed Plasma Concentration (Cmax) of Gemcitabine
NCT02978716 (28) [back to overview]Major Adverse Hematologic Event (MAHE) Rate
NCT02978716 (28) [back to overview]Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1
NCT02978716 (28) [back to overview]Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator
NCT02978716 (28) [back to overview]Duration of Exposure
NCT02978716 (28) [back to overview]Dose Modifications: Number of Participants With Cycle Delays
NCT02978716 (28) [back to overview]Relative Dose Intensity of Gemcitabine and Carboplatin
NCT02978716 (28) [back to overview]Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
NCT02978716 (28) [back to overview]Number of Participants With Grade 3 and 4 Hematologic Toxicities
NCT02978716 (28) [back to overview]Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
NCT02978716 (28) [back to overview]Dose Modifications: Number of Participants With Any Dose Interruptions
NCT02978716 (28) [back to overview]Dose Modifications - Number of Participants With Dose Reductions
NCT02978716 (28) [back to overview]Volume of Distribution at Steady State (Vss) of Free Carboplatin
NCT02978716 (28) [back to overview]Terminal Elimination Half-Life (t1/2) of Trilaciclib
NCT02978716 (28) [back to overview]Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator
NCT02978716 (28) [back to overview]All-cause Dose Reductions, Event Rate (Per Cycle)
NCT02983045 (3) [back to overview]Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window
NCT02983045 (3) [back to overview]Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window
NCT02983045 (3) [back to overview]Part 2 and Part 4: Objective Response Rate (ORR) Per RECIST 1.1 at Recommended Phase 2 Dose (RP2D)
NCT02985021 (1) [back to overview]Percentage of Patients Achieving >= 50% Reduction in PSA According to Prostate Cancer Working Group 3 (PCWG3) Criteria
NCT02998528 (4) [back to overview]Pathologic Complete Response (pCR) Rate
NCT02998528 (4) [back to overview]Major Pathologic Response (MPR) Rate
NCT02998528 (4) [back to overview]Time to Death or Distant Metastases (TTDM)
NCT02998528 (4) [back to overview]Event-Free Survival (EFS)
NCT03003962 (44) [back to overview]PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set
NCT03003962 (44) [back to overview]DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set
NCT03003962 (44) [back to overview]DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set
NCT03003962 (44) [back to overview]APF12 in PD-L1 TC >= 50% LREM Analysis Set
NCT03003962 (44) [back to overview]APF12 in PD-L1 TC >= 50% Analysis Set
NCT03003962 (44) [back to overview]APF12 in PD-L1 TC >= 25% LREM Analysis Set
NCT03003962 (44) [back to overview]Alive and Progression-Free at 12 Months (APF12)
NCT03003962 (44) [back to overview]OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set
NCT03003962 (44) [back to overview]OS at 24 Months
NCT03003962 (44) [back to overview]OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set
NCT03003962 (44) [back to overview]OS at 18 Months in PD-L1 TC >= 50% Analysis Set
NCT03003962 (44) [back to overview]OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set
NCT03003962 (44) [back to overview]OS at 18 Months
NCT03003962 (44) [back to overview]ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set
NCT03003962 (44) [back to overview]ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set
NCT03003962 (44) [back to overview]ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set
NCT03003962 (44) [back to overview]Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment
NCT03003962 (44) [back to overview]Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment
NCT03003962 (44) [back to overview]DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set
NCT03003962 (44) [back to overview]PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set
NCT03003962 (44) [back to overview]PFS2 in PD-L1 TC >= 25% LREM Analysis Set
NCT03003962 (44) [back to overview]Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)
NCT03003962 (44) [back to overview]PFS2 in PD-L1 TC >= 50% Analysis Set
NCT03003962 (44) [back to overview]Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status
NCT03003962 (44) [back to overview]Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set
NCT03003962 (44) [back to overview]PFS2 in PD-L1 TC >= 50% LREM Analysis Set
NCT03003962 (44) [back to overview]Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
NCT03003962 (44) [back to overview]Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)
NCT03003962 (44) [back to overview]Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab
NCT03003962 (44) [back to overview]Time From Randomization to Second Progression (PFS2)
NCT03003962 (44) [back to overview]OS at 24 Months in PD-L1 TC >= 50% Analysis Set
NCT03003962 (44) [back to overview]Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT03003962 (44) [back to overview]OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set
NCT03003962 (44) [back to overview]OS in Participants With LREM
NCT03003962 (44) [back to overview]OS in PD-L1 TC >= 50% Analysis Set
NCT03003962 (44) [back to overview]OS in PD-L1 TC >= 50% LREM Analysis Set
NCT03003962 (44) [back to overview]Overall Survival (OS)
NCT03003962 (44) [back to overview]PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set
NCT03003962 (44) [back to overview]Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set
NCT03003962 (44) [back to overview]Time to Deterioration of EORTC QLQ-C30
NCT03003962 (44) [back to overview]Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set
NCT03003962 (44) [back to overview]Time to Deterioration of EORTC QLQ-LC13
NCT03003962 (44) [back to overview]Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
NCT03003962 (44) [back to overview]Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set
NCT03029598 (9) [back to overview]Count of Adverse Events Evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.
NCT03029598 (9) [back to overview]Immune-related Best Overall Response (BOR) Assessed Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
NCT03029598 (9) [back to overview]Immune-related Progression-free Survival (PFS) Using irRECIST (Immune-related Response Evaluation Criteria In Solid Tumors) Derived From Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
NCT03029598 (9) [back to overview]Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining
NCT03029598 (9) [back to overview]Overall Survival (OS)
NCT03029598 (9) [back to overview]Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
NCT03029598 (9) [back to overview]Response Rate (RR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
NCT03029598 (9) [back to overview]Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
NCT03029598 (9) [back to overview]Best Overall Response (BOR)
NCT03029611 (1) [back to overview]Rate of Pathologic Complete Response (CR)
NCT03038100 (17) [back to overview]Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group in ITT Population
NCT03038100 (17) [back to overview]Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group in PD-L1-Positive Population
NCT03038100 (17) [back to overview]Overall Survival - ITT Population
NCT03038100 (17) [back to overview]Overall Survival - PD-L1-Positive Subpopulation
NCT03038100 (17) [back to overview]Percentage of Participants With Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery Group in PD-L1-Positive Population
NCT03038100 (17) [back to overview]Percentage of Participants With at Least One Adverse Event
NCT03038100 (17) [back to overview]Progression-Free Survival (PFS) Assessed by Investigator as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) - Intent-to-Treat (ITT) Population
NCT03038100 (17) [back to overview]Maximum Serum Concentration (Cmax) of Atezolizumab
NCT03038100 (17) [back to overview]Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
NCT03038100 (17) [back to overview]PFS Assessed by Investigator as Per RECIST v1.1 - Programmed Death-Ligand 1 (PD-L1)-Positive Subpopulation
NCT03038100 (17) [back to overview]Percentage of Participants With Deterioration in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group
NCT03038100 (17) [back to overview]Percentage of Participants With Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery Group in ITT Population
NCT03038100 (17) [back to overview]Percentage of Participants Who Remain Stable in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group
NCT03038100 (17) [back to overview]Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group
NCT03038100 (17) [back to overview]Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and Health Related Quality of Life (HRQoL) - Neoadjuvant Group
NCT03038100 (17) [back to overview]Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Abdominal Pain and Bloating - Neoadjuvant Group
NCT03038100 (17) [back to overview]Minimum Serum Concentration (Cmin) of Atezolizumab
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of Grade 3 or 4 Hematologic Laboratory Abnormalities
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of Infection Serious Adverse Events (SAEs)
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of IV Antibiotic Uses
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of Platelet Transfusion
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of RBC Transfusion on/After Week 5 (Proportion of Patients)
NCT03041311 (27) [back to overview]Occurrence of Granulocyte Colony-Stimulating Factor (G-CSF) Administration (Proportion of Patients)
NCT03041311 (27) [back to overview]Best Overall Response
NCT03041311 (27) [back to overview]Duration of Objective Response (Complete Response or Partial Response)
NCT03041311 (27) [back to overview]Duration of Study Drug Exposure (Induction Period and Maintenance Period)
NCT03041311 (27) [back to overview]Major Adverse Hematologic Events (MAHE) (Composite Endpoint)
NCT03041311 (27) [back to overview]Number of Cycles Completed (Induction Period and Maintenance Period)
NCT03041311 (27) [back to overview]Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Induction Period)
NCT03041311 (27) [back to overview]Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Maintenance Period)
NCT03041311 (27) [back to overview]Number of Participants With Any Dose Interruptions [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)
NCT03041311 (27) [back to overview]Number of Participants With Any Dose Reductions of Carboplatin and Etoposide (Induction Period)
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of Severe (Grade 4) Neutropenia
NCT03041311 (27) [back to overview]Progression-Free Survival
NCT03041311 (27) [back to overview]Relative Dose Intensity of Trilaciclib/Placebo, Carboplatin, Etoposide, Atezolizumab (Induction Period) and Atezolizumab (Maintenance Period)
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of Febrile Neutropenia
NCT03041311 (27) [back to overview]Overall Survival (OS)
NCT03041311 (27) [back to overview]Number of Participants With Any Missed Doses [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)
NCT03041311 (27) [back to overview]All-Cause Dose Reductions
NCT03041311 (27) [back to overview]Duration of Severe (Grade 4) Neutropenia in Cycle 1
NCT03041311 (27) [back to overview]Number of Participants With Any Interrupted Doses of Atezolizumab (Overall Treatment Period)
NCT03041311 (27) [back to overview]Number of Participants With Any Missed Doses of Atezolizumab (Overall Treatment Period)
NCT03041311 (27) [back to overview]Number of Participants With at Least 1 Occurrence of Erythropoiesis Stimulating Agent (ESA) Administration
NCT03043872 (32) [back to overview]OS in the Global Cohort; D + T + EP Compared With D + EP
NCT03043872 (32) [back to overview]Objective Response Rate (ORR) in the Global Cohort
NCT03043872 (32) [back to overview]Change From Baseline in Primary PRO Symptoms as Assessed by EORTC QLQ in the Global Cohort; D + T + EP Compared With EP
NCT03043872 (32) [back to overview]Change From Baseline in Primary PRO Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the China Cohort; D + T + EP Compared With EP
NCT03043872 (32) [back to overview]OS in the China Cohort; Assessed at China Cohort First Analysis; D + EP Compared With EP
NCT03043872 (32) [back to overview]Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13) in the Global Cohort
NCT03043872 (32) [back to overview]Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-LC13 in the China Cohort
NCT03043872 (32) [back to overview]ORR in the China Cohort
NCT03043872 (32) [back to overview]Time to Deterioration of HRQoL and PRO Symptoms, Assessed Using EORTC QLQ in the China Cohort
NCT03043872 (32) [back to overview]Change From Baseline in Primary Symptoms as Assessed by EORTC QLQ in the China Cohort; D + EP Compared With EP
NCT03043872 (32) [back to overview]OS in the China Cohort; D + T + EP Compared With D + EP
NCT03043872 (32) [back to overview]Time to Deterioration of Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) in the Global Cohort
NCT03043872 (32) [back to overview]PK of Tremelimumab; Peak and Trough Serum Concentrations in the Global Cohort
NCT03043872 (32) [back to overview]PK of Tremelimumab; Peak and Trough Serum Concentrations in the China Cohort
NCT03043872 (32) [back to overview]Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations in the Global Cohort
NCT03043872 (32) [back to overview]OS in the Global Cohort; Assessed at Global Cohort Final Analysis; D + EP Compared With EP and D + T + EP Compared With EP
NCT03043872 (32) [back to overview]Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab in the Global Cohort
NCT03043872 (32) [back to overview]Number of Patients With ADA Response to Tremelimumab in the Global Cohort
NCT03043872 (32) [back to overview]Number of Patients With ADA Response to Tremelimumab in the China Cohort
NCT03043872 (32) [back to overview]Number of Patients With ADA Response to Durvalumab in the China Cohort
NCT03043872 (32) [back to overview]OS in the China Cohort; Assessed at China Cohort Second Analysis; D + EP Compared With EP and D + T + EP Compared With EP
NCT03043872 (32) [back to overview]OS18 in the China Cohort
NCT03043872 (32) [back to overview]Overall Survival (OS) in the Global Cohort; Assessed at Global Cohort Interim Analysis; D + EP Compared With EP
NCT03043872 (32) [back to overview]Percentage of Patients Alive and Progression Free at 12 Months (APF12) in the Global Cohort
NCT03043872 (32) [back to overview]Percentage of Patients Alive and Progression Free at 6 Months (APF6) in the Global Cohort
NCT03043872 (32) [back to overview]Percentage of Patients Alive at 18 Months (OS18) in the Global Cohort
NCT03043872 (32) [back to overview]PFS in the China Cohort
NCT03043872 (32) [back to overview]Progression-Free Survival (PFS) in the Global Cohort
NCT03043872 (32) [back to overview]Change From Baseline in Primary Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the Global Cohort; D + EP Compared With EP
NCT03043872 (32) [back to overview]PK of Durvalumab; Peak and Trough Serum Concentrations in the China Cohort
NCT03043872 (32) [back to overview]APF12 in the China Cohort
NCT03043872 (32) [back to overview]APF6 in the China Cohort
NCT03057366 (15) [back to overview]Part A: AUClast: Area Under the Plasma and Whole Blood TRA Concentration Curve From Time 0 to Time of the Last Quantifiable Concentration for [14C]-Pevonedistat Drug-related Material
NCT03057366 (15) [back to overview]Part A: AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Pevonedistat
NCT03057366 (15) [back to overview]Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
NCT03057366 (15) [back to overview]Part A: Renal Clearance (CLR) for Pevonedistat
NCT03057366 (15) [back to overview]Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval
NCT03057366 (15) [back to overview]Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment
NCT03057366 (15) [back to overview]Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
NCT03057366 (15) [back to overview]Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood TRA Concentration (Cmax) for [14C]-Pevonedistat Drug-related Material
NCT03057366 (15) [back to overview]Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose
NCT03057366 (15) [back to overview]Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval
NCT03057366 (15) [back to overview]Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body
NCT03057366 (15) [back to overview]Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat
NCT03057366 (15) [back to overview]Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces
NCT03057366 (15) [back to overview]Part A: Cmax: Maximum Observed Plasma and Whole Blood TRA Concentration for [14C]-Pevonedistat Drug-related Material
NCT03057366 (15) [back to overview]Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat
NCT03066778 (9) [back to overview]Change From Baseline at Week 18 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale
NCT03066778 (9) [back to overview]Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)
NCT03066778 (9) [back to overview]Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE 4.03)
NCT03066778 (9) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT03066778 (9) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
NCT03066778 (9) [back to overview]Overall Survival (OS)
NCT03066778 (9) [back to overview]Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
NCT03066778 (9) [back to overview]Time to True Deterioration (TTD) in the Composite Endpoint of Cough, Chest Pain, and Dyspnea Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Lung Cancer Module 13 (QLQ-LC13)
NCT03066778 (9) [back to overview]Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
NCT03067610 (7) [back to overview]Total Number of Participants With Gastrostomy Dependence
NCT03067610 (7) [back to overview]Probability of Locoregional or Distant Tumor Failure
NCT03067610 (7) [back to overview]Quality of Life (QOL) Patient Reported Outcomes (PRO)
NCT03067610 (7) [back to overview]Progression-free Survival
NCT03067610 (7) [back to overview]Overall Survival
NCT03067610 (7) [back to overview]Number of Patients With Solitary Elective Volume Recurrence
NCT03067610 (7) [back to overview]Number of Participants With Definite, Possible, and Probable Protocol-related Toxicities (Grade 3-5)
NCT03085914 (3) [back to overview]Phases 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)
NCT03085914 (3) [back to overview]Phases 1 and 2: Objective Response Rate (ORR)
NCT03085914 (3) [back to overview]Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
NCT03117049 (6) [back to overview]Duration of Response (DOR [as Assessed by the IRRC])
NCT03117049 (6) [back to overview]Overall Survival (OS)
NCT03117049 (6) [back to overview]Disease Control Rate (DCR [as Assessed by the IRRC])
NCT03117049 (6) [back to overview]Best Overall Response (BOR [as Assessed by the IRRC])
NCT03117049 (6) [back to overview]Progression Free Survival (PFS) as Assessed by the Independent Radiology Review Committee (IRRC)
NCT03117049 (6) [back to overview]Objective Response Rate (ORR [as Assessed by the IRRC])
NCT03121352 (4) [back to overview]Disease Control Rate (DCR) in Patients Treated With CNP
NCT03121352 (4) [back to overview]Progression-free Survival (PFS) in Patients Treated With CNP
NCT03121352 (4) [back to overview]Duration of Response in Patients Treated With CNP
NCT03121352 (4) [back to overview]Overall Response Rate (ORR) in Patients Treated With CNP
NCT03128008 (4) [back to overview]Overall Survival With an Accelerated and Adaptive RT Approach.
NCT03128008 (4) [back to overview]Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach.
NCT03128008 (4) [back to overview]The Number of Participants Eligible for an RT Boost After Completing a Standard Dose of RT (60 Gy), Delivered in an Accelerated Fashion (6 Fractions/Week) With Concurrent Chemotherapy
NCT03128008 (4) [back to overview]Number of Participants With Local Control With an Accelerated and Adaptive RT Approach
NCT03138889 (4) [back to overview]Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a
NCT03138889 (4) [back to overview]Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] for Dose Optimization Cohort 1a.
NCT03138889 (4) [back to overview]Objective Response Rate (ORR) Per Investigator's Assessment by RECIST 1.1 of NKTR-214 at a Dose of 0.006 mg/kg With Pembrolizumab and Platinum-based Chemotherapy for Dose Expansion Cohorts 4+5.
NCT03138889 (4) [back to overview]Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by RECIST 1.1 of NKTR-214 Plus Pembrolizumab for Dose Expansion Cohorts 2 and 3.
NCT03164616 (13) [back to overview]Time to Deterioration of Global Health Status / Health-Related Quality of Life (HRQoL) and Patient Reported Outcome (PRO) Symptoms, Assessed Using European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)
NCT03164616 (13) [back to overview]PK of Tremelimumab; Peak and Trough Serum Concentrations
NCT03164616 (13) [back to overview]Time From Randomization to Second Progression (PFS2)
NCT03164616 (13) [back to overview]Progression-Free Survival (PFS); D + SoC Compared With SoC Alone
NCT03164616 (13) [back to overview]PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
NCT03164616 (13) [back to overview]Overall Survival (OS); D + SoC Compared With SoC Alone
NCT03164616 (13) [back to overview]OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC
NCT03164616 (13) [back to overview]Objective Response Rate (ORR)
NCT03164616 (13) [back to overview]Duration of Response (DoR)
NCT03164616 (13) [back to overview]Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations
NCT03164616 (13) [back to overview]Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab
NCT03164616 (13) [back to overview]Number of Patients With ADA Response to Tremelimumab
NCT03164616 (13) [back to overview]Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)
NCT03174275 (1) [back to overview]Pathologic Complete Response Rate (pCRR) After Induction Chemotherapy With Carboplatin, Nab-paclitaxel, and Durvalumab in Previously Untreated Stage III and IV SCCHN Amenable to Surgical Resection
NCT03189446 (2) [back to overview]Number of Patients Completing the Protocol
NCT03189446 (2) [back to overview]Frequency of Adverse Events Related to Acute Toxicity During Treatment
NCT03194373 (4) [back to overview]Median Overall Survival Time
NCT03194373 (4) [back to overview]Median Progression Free Survival Time
NCT03194373 (4) [back to overview]Percent Disease Control Rate (DCR)
NCT03194373 (4) [back to overview]Number of Treatment-related Toxicities
NCT03206203 (5) [back to overview]Clinical Benefit Rate (CBR)
NCT03206203 (5) [back to overview]Duration of Response (DOR)
NCT03206203 (5) [back to overview]Overall Response Rate (ORR)
NCT03206203 (5) [back to overview]Progression Free Survival (PFS)
NCT03206203 (5) [back to overview]Overall Survival (OS)
NCT03215706 (8) [back to overview]Overall Survival (OS)
NCT03215706 (8) [back to overview]Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression
NCT03215706 (8) [back to overview]OS by PD-L1 Tumor Cell Expression
NCT03215706 (8) [back to overview]PFS by BICR by PD-L1 Tumor Cell Expression
NCT03215706 (8) [back to overview]Objective Response Rate (ORR) by BICR
NCT03215706 (8) [back to overview]Duration of Response (DoR)
NCT03215706 (8) [back to overview]Progression Free Survival (PFS) by BICR
NCT03215706 (8) [back to overview]Time to Response (TTR)
NCT03256136 (5) [back to overview]Progression Free Survival (PFS)
NCT03256136 (5) [back to overview]Overall Survival (OS)
NCT03256136 (5) [back to overview]Objective Response Rate (ORR), Presented in Numbers of Participants
NCT03256136 (5) [back to overview]Disease Control Rate (DCR), Presented in Numbers of Participants
NCT03256136 (5) [back to overview]Duration Of Response
NCT03278626 (2) [back to overview]Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)
NCT03278626 (2) [back to overview]Phase 1: Number of Unacceptable Toxicity (UT) Events
NCT03279237 (4) [back to overview]Pathologic Complete Response Rate
NCT03279237 (4) [back to overview]The Completion Rate of Chemotherapy in Combination With Chemoradiation
NCT03279237 (4) [back to overview]Clinical Response Rate
NCT03279237 (4) [back to overview]Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
NCT03296163 (5) [back to overview]Incidence of Treatment-emergent Adverse Events (TEAEs)
NCT03296163 (5) [back to overview]Immunogenicity Assessments (Anti-drug Antibodies [ADA] and Neutralizing Antibodies [NAb])
NCT03296163 (5) [back to overview]Progression-free Survival (PFS)
NCT03296163 (5) [back to overview]Objective Response Rate (ORR) at Week 18
NCT03296163 (5) [back to overview]Overall Survival (OS)
NCT03301350 (5) [back to overview]Number of Cycles of Chemotherapy Administered
NCT03301350 (5) [back to overview]Delays of Administered Chemotherapy
NCT03301350 (5) [back to overview]Total Dose of Chemotherapy Administered
NCT03301350 (5) [back to overview]Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate
NCT03301350 (5) [back to overview]Number of Treatment-related Toxicities Experienced by Participants
NCT03307785 (158) [back to overview]Part B: Vz of TSR-042
NCT03307785 (158) [back to overview]Part B: Vss of TSR-042
NCT03307785 (158) [back to overview]Part B: Tmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part B: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
NCT03307785 (158) [back to overview]Part B: Ctau,ss of TSR-042
NCT03307785 (158) [back to overview]Part B: Cmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part B: CL of TSR-042
NCT03307785 (158) [back to overview]Part B: AUCss of TSR-042
NCT03307785 (158) [back to overview]Part B: AUC0-t of TSR-042
NCT03307785 (158) [back to overview]Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib
NCT03307785 (158) [back to overview]Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib
NCT03307785 (158) [back to overview]Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042
NCT03307785 (158) [back to overview]Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042
NCT03307785 (158) [back to overview]Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042
NCT03307785 (158) [back to overview]Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042
NCT03307785 (158) [back to overview]Part A: Tmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part A: Tmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part A: Tmax at Steady State (Tmax,ss) of Niraparib
NCT03307785 (158) [back to overview]Part A: Tmax at Steady State (Tmax,ss) of Niraparib
NCT03307785 (158) [back to overview]Part A: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs) and Adverse Events of Special Interest (AESIs)
NCT03307785 (158) [back to overview]Part A: Ctau,ss of TSR-042
NCT03307785 (158) [back to overview]Part A: Ctau,ss of TSR-042
NCT03307785 (158) [back to overview]Part A: Ctau at Steady State (Ctau,ss) of Niraparib
NCT03307785 (158) [back to overview]Part A: Cmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part A: Cmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part A: Cmax at Steady State (Cmax,ss) of Niraparib
NCT03307785 (158) [back to overview]Part A: Cmax at Steady State (Cmax,ss) of Niraparib
NCT03307785 (158) [back to overview]Part A: Clearance After Oral Administration (CL/F) of Niraparib
NCT03307785 (158) [back to overview]Part A: Clearance After Oral Administration (CL/F) of Niraparib
NCT03307785 (158) [back to overview]Part A: Clearance After Intravenous Administration (CL) of TSR-042
NCT03307785 (158) [back to overview]Part A: Clearance After Intravenous Administration (CL) of TSR-042
NCT03307785 (158) [back to overview]Part A: AUCss of TSR-042
NCT03307785 (158) [back to overview]Part A: AUCss of TSR-042
NCT03307785 (158) [back to overview]Part A: AUC(0-t) of TSR-042
NCT03307785 (158) [back to overview]Part A: AUC(0-t) of TSR-042
NCT03307785 (158) [back to overview]Part F: Vz of TSR-042
NCT03307785 (158) [back to overview]Part F: Vz of TSR-022
NCT03307785 (158) [back to overview]Part F: Vss of TSR-042
NCT03307785 (158) [back to overview]Part F: Vss of TSR-022
NCT03307785 (158) [back to overview]Part F: Tmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part F: Tmax,ss of TSR-022
NCT03307785 (158) [back to overview]Part F: Tmax of TSR-042
NCT03307785 (158) [back to overview]Part F: Tmax of TSR-022
NCT03307785 (158) [back to overview]Part F: Objective Response Rate
NCT03307785 (158) [back to overview]Part F: Number of Participants With Positive Anti-TSR-042 Antibodies
NCT03307785 (158) [back to overview]Part F: Number of Participants With Positive Anti-TSR-022 Antibodies
NCT03307785 (158) [back to overview]Part F: Number of Participants With DLT
NCT03307785 (158) [back to overview]Part F: Duration of Response
NCT03307785 (158) [back to overview]Part F: Disease Control Rate
NCT03307785 (158) [back to overview]Part F: Ctau,ss of TSR-042
NCT03307785 (158) [back to overview]Part F: Ctau,ss of TSR-022
NCT03307785 (158) [back to overview]Part C: AUCss of Niraparib
NCT03307785 (158) [back to overview]Part C: AUC(0-infinity) of TSR-042
NCT03307785 (158) [back to overview]Part C: AUC(0-infinity) of Niraparib
NCT03307785 (158) [back to overview]Part C: Cmax of TSR-042
NCT03307785 (158) [back to overview]Part C: Ctau of Niraparib
NCT03307785 (158) [back to overview]Part C: Ctau of TSR-042
NCT03307785 (158) [back to overview]Part C: Disease Control Rate
NCT03307785 (158) [back to overview]Part C: Number of Participants With DLT
NCT03307785 (158) [back to overview]Part C: Number of Participants With Positive Anti-TSR-042 Antibodies
NCT03307785 (158) [back to overview]Part C: Objective Response Rate
NCT03307785 (158) [back to overview]Part C: Progression-free Survival
NCT03307785 (158) [back to overview]Part C: Tmax of Niraparib
NCT03307785 (158) [back to overview]Part C: Tmax of TSR-042
NCT03307785 (158) [back to overview]Part D: AUC(0-infinity) of TSR-042
NCT03307785 (158) [back to overview]Part D: Cmax of TSR-042
NCT03307785 (158) [back to overview]Part D: Ctau of TSR-042
NCT03307785 (158) [back to overview]Part D: Disease Control Rate
NCT03307785 (158) [back to overview]Part B: Tmax of TSR-042
NCT03307785 (158) [back to overview]Part B: Progression-free Survival
NCT03307785 (158) [back to overview]Part B: Objective Response Rate
NCT03307785 (158) [back to overview]Part D: Number of Participants With DLT
NCT03307785 (158) [back to overview]Part D: Number of Participants With Positive Anti-TSR-042 Antibodies
NCT03307785 (158) [back to overview]Part B: Number of Participants With Positive Anti-TSR-042 Antibodies
NCT03307785 (158) [back to overview]Part B: Number of Participants With DLT
NCT03307785 (158) [back to overview]Part B: Disease Control Rate
NCT03307785 (158) [back to overview]Part B: Ctau of TSR-042
NCT03307785 (158) [back to overview]Part B: Cmax of TSR-042
NCT03307785 (158) [back to overview]Part B: AUC(0-infinity) of TSR-042
NCT03307785 (158) [back to overview]Part A: Tmax of TSR-042
NCT03307785 (158) [back to overview]Part A: Time to Reach Maximum Plasma Concentration (Tmax) of Niraparib
NCT03307785 (158) [back to overview]Part A: Progression-free Survival
NCT03307785 (158) [back to overview]Part A: Observed Concentration at the End of the Dosing Interval (Ctau) of Niraparib
NCT03307785 (158) [back to overview]Part A: Objective Response Rate
NCT03307785 (158) [back to overview]Part A: Number of Participants With Positive Anti-TSR-042 Antibodies
NCT03307785 (158) [back to overview]Part A: Number of Participants With Dose-limiting Toxicity (DLT)
NCT03307785 (158) [back to overview]Part A: Maximum Observed Plasma (Cmax) of Niraparib
NCT03307785 (158) [back to overview]Part A: Duration of Response
NCT03307785 (158) [back to overview]Part A: Disease Control Rate
NCT03307785 (158) [back to overview]Part A: Ctau of TSR-042
NCT03307785 (158) [back to overview]Part A: Cmax of TSR-042
NCT03307785 (158) [back to overview]Part A: AUC(0-infinity) of TSR-042
NCT03307785 (158) [back to overview]Part A: AUC at Steady State (AUCss) of Niraparib
NCT03307785 (158) [back to overview]Part A: Area Under the Plasma Concentration From Time Zero to Infinity (AUC[0-infinity]) of Niraparib
NCT03307785 (158) [back to overview]Part D: Objective Response Rate
NCT03307785 (158) [back to overview]Part D: Progression-free Survival
NCT03307785 (158) [back to overview]Part D: Tmax of TSR-042
NCT03307785 (158) [back to overview]Part E: AUC(0-infinity) of TSR-042
NCT03307785 (158) [back to overview]Part E: AUC0-t of TSR-042
NCT03307785 (158) [back to overview]Part E: AUCss of TSR-042
NCT03307785 (158) [back to overview]Part E: CL of TSR-042
NCT03307785 (158) [back to overview]Part E: Cmax of TSR-042
NCT03307785 (158) [back to overview]Part E: Cmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part E: Ctau of TSR-042
NCT03307785 (158) [back to overview]Part E: Ctau,ss of TSR-042
NCT03307785 (158) [back to overview]Part E: Disease Control Rate
NCT03307785 (158) [back to overview]Part E: Duration of Response
NCT03307785 (158) [back to overview]Part E: Number of Participants With DLT
NCT03307785 (158) [back to overview]Part E: Number of Participants With Positive Anti-TSR-042 Antibodies
NCT03307785 (158) [back to overview]Part E: Objective Response Rate
NCT03307785 (158) [back to overview]Part C: Cmax of Niraparib
NCT03307785 (158) [back to overview]Part E: Progression-free Survival
NCT03307785 (158) [back to overview]Part E: Tmax of TSR-042
NCT03307785 (158) [back to overview]Part E: Tmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part E: Vss of TSR-042
NCT03307785 (158) [back to overview]Part E: Vz of TSR-042
NCT03307785 (158) [back to overview]Part F: AUC(0-infinity) of TSR-022
NCT03307785 (158) [back to overview]Part F: Progression-free Survival
NCT03307785 (158) [back to overview]Part F: AUC(0-infinity) of TSR-042
NCT03307785 (158) [back to overview]Part F: AUC0-t of TSR-022
NCT03307785 (158) [back to overview]Part F: AUC0-t of TSR-042
NCT03307785 (158) [back to overview]Part F: AUCss of TSR-022
NCT03307785 (158) [back to overview]Part A: Area Under the Plasma Concentration From Time Zero to t (AUC[0-t]) of Niraparib
NCT03307785 (158) [back to overview]Part F: AUCss of TSR-042
NCT03307785 (158) [back to overview]Part F: CL of TSR-022
NCT03307785 (158) [back to overview]Part F: CL of TSR-042
NCT03307785 (158) [back to overview]Part F: Cmax of TSR-022
NCT03307785 (158) [back to overview]Part F: Cmax of TSR-042
NCT03307785 (158) [back to overview]Part F: Cmax,ss of TSR-022
NCT03307785 (158) [back to overview]Part F: Cmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part F: Ctau of TSR-022
NCT03307785 (158) [back to overview]Part F: Ctau of TSR-042
NCT03307785 (158) [back to overview]Part F: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
NCT03307785 (158) [back to overview]Part E: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
NCT03307785 (158) [back to overview]Part D: Vz of TSR-042
NCT03307785 (158) [back to overview]Part D: Vss of TSR-042
NCT03307785 (158) [back to overview]Part D: Tmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part D: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
NCT03307785 (158) [back to overview]Part D: Ctau,ss of TSR-042
NCT03307785 (158) [back to overview]Part D: Cmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part D: CL of TSR-042
NCT03307785 (158) [back to overview]Part D: AUCss of TSR-042
NCT03307785 (158) [back to overview]Part D: AUC0-t of TSR-042
NCT03307785 (158) [back to overview]Part C: Vz/F of Niraparib
NCT03307785 (158) [back to overview]Part C: Vz of TSR-042
NCT03307785 (158) [back to overview]Part C: Vss of TSR-042
NCT03307785 (158) [back to overview]Part C: Tmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part C: Tmax,ss of Niraparib
NCT03307785 (158) [back to overview]Part C: Number of Participants With Non-serious TEAEs, STEAEs and AESIs
NCT03307785 (158) [back to overview]Part C: Ctau,ss of TSR-042
NCT03307785 (158) [back to overview]Part C: Ctau,ss of Niraparib
NCT03307785 (158) [back to overview]Part C: Cmax,ss of TSR-042
NCT03307785 (158) [back to overview]Part C: Cmax,ss of Niraparib
NCT03307785 (158) [back to overview]Part C: CL/F of Niraparib
NCT03307785 (158) [back to overview]Part C: CL of TSR-042
NCT03307785 (158) [back to overview]Part C: AUCss of TSR-042
NCT03307785 (158) [back to overview]Part C: AUC0-t of TSR-042
NCT03307785 (158) [back to overview]Part C: AUC0-t of Niraparib
NCT03317496 (13) [back to overview]Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment
NCT03317496 (13) [back to overview]Number of Participants With Treatment Related TEAEs
NCT03317496 (13) [back to overview]Overall Survival (OS)
NCT03317496 (13) [back to overview]Serum Concentration of Avelumab
NCT03317496 (13) [back to overview]Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03
NCT03317496 (13) [back to overview]Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression
NCT03317496 (13) [back to overview]Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
NCT03317496 (13) [back to overview]Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT)
NCT03317496 (13) [back to overview]Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment
NCT03317496 (13) [back to overview]Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue
NCT03317496 (13) [back to overview]Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment
NCT03317496 (13) [back to overview]Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade
NCT03317496 (13) [back to overview]Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs
NCT03329378 (5) [back to overview]Number of Non-cardiac Toxicities
NCT03329378 (5) [back to overview]Number of Participants With Pathologic Complete Response (pCR)
NCT03329378 (5) [back to overview]Number of Participants With Breast Conservation
NCT03329378 (5) [back to overview]Number of Participants Alive at the End of the Study
NCT03329378 (5) [back to overview]Number of Cardiac Toxicity Events
NCT03329911 (1) [back to overview]Overall Response Rate
NCT03330106 (9) [back to overview]Part A: Change From Time-matched Baseline in QRS After Pevonedistat Administration
NCT03330106 (9) [back to overview]Part A: Change From Time-matched Baseline in PR After Pevonedistat Administration
NCT03330106 (9) [back to overview]Part A: Change From Time-matched Baseline in Individual Corrected QT Interval (QTcI) After Pevonedistat Administration
NCT03330106 (9) [back to overview]Part A: Change From Time-matched Baseline in Heart Rate (HR) After Pevonedistat Administration
NCT03330106 (9) [back to overview]Part A: Change From Time-matched Baseline in Fridericia-corrected QT Interval (QTcF) After Pevonedistat Administration
NCT03330106 (9) [back to overview]Part B: Overall Response Rate (ORR)
NCT03330106 (9) [back to overview]Part A: Terminal Phase Elimination Half-life (t1/2) for Pevonedistat
NCT03330106 (9) [back to overview]Part A: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for Pevonedistat
NCT03330106 (9) [back to overview]Part A: Cmax: Maximum Observed Plasma Concentration for Pevonedistat
NCT03358472 (3) [back to overview]Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen
NCT03358472 (3) [back to overview]Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)
NCT03358472 (3) [back to overview]Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs
NCT03382561 (3) [back to overview]Overall Survival (OS)
NCT03382561 (3) [back to overview]Progression-free Survival (PFS)
NCT03382561 (3) [back to overview]Response Rate
NCT03394885 (8) [back to overview]Number of Participants With Pathologic Complete Remission
NCT03394885 (8) [back to overview]Safety: Incidence of Post Chemotherapy Surgical Debulking
NCT03394885 (8) [back to overview]Safety: Dose Intensity
NCT03394885 (8) [back to overview]Safety: Incidence of Dose Modifications
NCT03394885 (8) [back to overview]Translational: Fold Change in Cytokine Expression
NCT03394885 (8) [back to overview]Progression Free Survival Rate
NCT03394885 (8) [back to overview]Overall Survival Rate
NCT03394885 (8) [back to overview]Number of Participants With a Complete or Partial Response as Measured by RECIST (Response Evaluation Criteria in Solid Tumors)
NCT03414684 (27) [back to overview]Objective Response Rate by RECIST 1.1 Among BRCA-mutant Patients
NCT03414684 (27) [back to overview]Second-course Time to Objective Response Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab
NCT03414684 (27) [back to overview]Objective Response Rate by RECIST 1.1 Among PD-L1-positive Patients
NCT03414684 (27) [back to overview]Objective Response Rate by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1
NCT03414684 (27) [back to overview]Second-course Objective Response Rate by irRC Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab
NCT03414684 (27) [back to overview]Second-course Progression-free Survival Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab
NCT03414684 (27) [back to overview]Time to Objective Response Among PD-L1-positive Patients
NCT03414684 (27) [back to overview]Second-course Overall Survival Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab
NCT03414684 (27) [back to overview]Second-course Objective Response Rate by RECIST 1.1 Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab
NCT03414684 (27) [back to overview]Second-course Duration of Response Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab
NCT03414684 (27) [back to overview]Duration of Response
NCT03414684 (27) [back to overview]Clinical Benefit Rate Among PD-L1-positive Patients
NCT03414684 (27) [back to overview]Clinical Benefit Rate Among BRCA-mutant Patients
NCT03414684 (27) [back to overview]Clinical Benefit Rate
NCT03414684 (27) [back to overview]Overall Survival
NCT03414684 (27) [back to overview]Overall Survival Among BRCA-mutant Patients
NCT03414684 (27) [back to overview]Second-course Clinical Benefit Rate Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab
NCT03414684 (27) [back to overview]Overall Survival Among PD-L1-positive Patients
NCT03414684 (27) [back to overview]Progression-free Survival
NCT03414684 (27) [back to overview]Progression-free Survival Among PD-L1-positive Patients
NCT03414684 (27) [back to overview]Progression-free Survival Among BRCA-mutant Patients
NCT03414684 (27) [back to overview]Time to Objective Response Among BRCA-mutant Patients
NCT03414684 (27) [back to overview]Time to Objective Response
NCT03414684 (27) [back to overview]Objective Response Rate by irRC Among PD-L1-positive Patients
NCT03414684 (27) [back to overview]Objective Response Rate by Immune-Related Response Criteria (irRC)
NCT03414684 (27) [back to overview]Duration of Response Among PD-L1-positive Patients
NCT03414684 (27) [back to overview]Duration of Response Among BRCA-mutant Patients
NCT03473743 (3) [back to overview]Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment
NCT03473743 (3) [back to overview]Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs)
NCT03473743 (3) [back to overview]Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs)
NCT03480750 (6) [back to overview]Overall Survival
NCT03480750 (6) [back to overview]Maximum Plasma Concentration [Cmax] of Trientine
NCT03480750 (6) [back to overview]Maximum Tolerated Dose, MTD
NCT03480750 (6) [back to overview]Number of Participants With Dose-Limiting Toxicity (DLT)
NCT03480750 (6) [back to overview]Percentage of Participants With Measurable Tumor Treatment Response Assessed by RECIST Criteria 1.1
NCT03480750 (6) [back to overview]Progression-free Survival
NCT03486314 (7) [back to overview]Part A: Terminal Disposition Phase Half-life (T1/2z) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
NCT03486314 (7) [back to overview]Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
NCT03486314 (7) [back to overview]Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
NCT03486314 (7) [back to overview]Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
NCT03486314 (7) [back to overview]Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment
NCT03486314 (7) [back to overview]Part A: Volume of Distribution at Steady State After Intravenous Administration (Vss) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
NCT03486314 (7) [back to overview]Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)
NCT03499899 (27) [back to overview]All Collected Deaths
NCT03499899 (27) [back to overview]Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1
NCT03499899 (27) [back to overview]Progression Free Survival (PFS)
NCT03499899 (27) [back to overview]PK Parameter, Cmax of Carboplatin (Ultrafilterable Platinum)
NCT03499899 (27) [back to overview]PK Parameter, Cmax of Carboplatin (Total Platinum)
NCT03499899 (27) [back to overview]Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1
NCT03499899 (27) [back to overview]PK Parameter, AUClast of PDR001
NCT03499899 (27) [back to overview]Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1
NCT03499899 (27) [back to overview]Overall Survival (OS)
NCT03499899 (27) [back to overview]PK Parameter, Cmax of LAG525
NCT03499899 (27) [back to overview]PK Parameter, Cmax of PDR001
NCT03499899 (27) [back to overview]PK Parameter, Tmax of Carboplatin (Total Platinum)
NCT03499899 (27) [back to overview]PK Parameter, Tmax of Carboplatin (Ultrafilterable Platinum)
NCT03499899 (27) [back to overview]PK Parameter, AUClast of LAG525
NCT03499899 (27) [back to overview]PK Parameter, Tmax of PDR001
NCT03499899 (27) [back to overview]Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1
NCT03499899 (27) [back to overview]PK Parameter, Tmax of LAG525
NCT03499899 (27) [back to overview]PK Parameter, AUClast of Carboplatin (Ultrafilterable Platinum)
NCT03499899 (27) [back to overview]PK Parameter, AUClast of Carboplatin (Total Platinum)
NCT03499899 (27) [back to overview]PK Parameter, AUC0-4h of Carboplatin (Total Platinum)
NCT03499899 (27) [back to overview]PK Parameter, AUC0-504h of PDR001
NCT03499899 (27) [back to overview]PK Parameter, AUC0-4h of Carboplatin (Ultrafilterable Platinum)
NCT03499899 (27) [back to overview]Pharmacokinetics (PK) Parameter, Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504h) of LAG525
NCT03499899 (27) [back to overview]Number of Participants With Anti-drug Antibodies (ADA) on Treatment for PDR001
NCT03499899 (27) [back to overview]Number of Participants With Anti-drug Antibodies (ADA) on Treatment for LAG525
NCT03499899 (27) [back to overview]Number of Participants With Anti-drug Antibodies (ADA) at Baseline for PDR001
NCT03499899 (27) [back to overview]Number of Participants With Anti-drug Antibodies (ADA) at Baseline for LAG525
NCT03594747 (1) [back to overview]Progression-free Survival (PFS) by Independent Review Committee (IRC) Assessment
NCT03629925 (6) [back to overview]OS (Overall Survival)
NCT03629925 (6) [back to overview]DCR (Disease Control Rate)
NCT03629925 (6) [back to overview]DOR (Duration of Response)
NCT03629925 (6) [back to overview]ORR(Objective Response Rate)
NCT03629925 (6) [back to overview]TTR (Time to Response)
NCT03629925 (6) [back to overview]PFS(Progression Free Survival)
NCT03631784 (4) [back to overview]Number of Participants Who Discontinued From Study Treatment Due to an AE
NCT03631784 (4) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT03631784 (4) [back to overview]Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT03631784 (4) [back to overview]Percentage of Participants Who Developed Grade 3 or Higher Pneumonitis
NCT03635489 (18) [back to overview]Duration of Response (DOR)
NCT03635489 (18) [back to overview]Percentage of Participants With Adverse Events (AEs)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Role)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Social)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Social)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Physical)
NCT03635489 (18) [back to overview]Progression-Free Survival (PFS)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Bloating
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Physical)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Emotional)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Abdominal Pain
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Abdominal Pain
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Bloating
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Role)
NCT03635489 (18) [back to overview]Pecentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Health Related Quality of Life (HRQoL)
NCT03635489 (18) [back to overview]Pecentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Health Related Quality of Life (HRQoL)
NCT03635489 (18) [back to overview]Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Emotional)
NCT03635489 (18) [back to overview]Objective Response Rate (ORR)
NCT03635567 (15) [back to overview]PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS ≥10
NCT03635567 (15) [back to overview]PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)
NCT03635567 (15) [back to overview]Number of Participants Who Experienced a Serious AE (SAE)
NCT03635567 (15) [back to overview]Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator
NCT03635567 (15) [back to overview]PFS Per RECIST 1.1 as Assessed by Investigator in All Participants
NCT03635567 (15) [back to overview]Number of Participants Who Experienced an Immune-related AE (irAE)
NCT03635567 (15) [back to overview]Number of Participants Who Discontinued Study Treatment Due to an AE
NCT03635567 (15) [back to overview]OS in All Participants
NCT03635567 (15) [back to overview]OS in Participants With PD-L1 CPS ≥10
NCT03635567 (15) [back to overview]Overall Survival (OS) in Participants With PD-L1 CPS ≥1
NCT03635567 (15) [back to overview]Number of Participants With a 10-point Change From Baseline in Quality of Life (QoL) Based on the European Organisation for the Research & Treatment of Cancer (EORTC) QoL Questionnaire-30 (QLQ-C30) Combined Global Score
NCT03635567 (15) [back to overview]Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator
NCT03635567 (15) [back to overview]Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1
NCT03635567 (15) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT03635567 (15) [back to overview]Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator
NCT03664024 (6) [back to overview]Overall Survival (OS)
NCT03664024 (6) [back to overview]Progression Free Survival (PFS)
NCT03664024 (6) [back to overview]Tumor Mutation Burden (TMB) in Cell-free Circulating Tumor Deoxyribonucleic Acid (ctDNA)
NCT03664024 (6) [back to overview]Percentage of Participants Who Experienced One or More Adverse Events (AEs)
NCT03664024 (6) [back to overview]Percentage of Participants Discontinuing Study Intervention Due to an AE.
NCT03664024 (6) [back to overview]Objective Response Rate
NCT03704467 (5) [back to overview]Part A: Time to Progression (TTP)
NCT03704467 (5) [back to overview]Part A: Progression-Free Survival (PFS)
NCT03704467 (5) [back to overview]Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs
NCT03704467 (5) [back to overview]Part A: Number of Participants With Confirmed Best Overall Response (BOR)
NCT03704467 (5) [back to overview]Part A: Number of Participants With Dose Limiting Toxicities (DLTs)
NCT03713944 (5) [back to overview]Disease Control Rate
NCT03713944 (5) [back to overview]Progression Free Survival
NCT03713944 (5) [back to overview]Number of Participants With Adverse Events
NCT03713944 (5) [back to overview]Overall Response Rate
NCT03713944 (5) [back to overview]Overall Survival
NCT03717155 (11) [back to overview]Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
NCT03717155 (11) [back to overview]Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator
NCT03717155 (11) [back to overview]Serum Trough Concentration Levels (Ctrough) of Avelumab
NCT03717155 (11) [back to overview]Serum Trough Concentration Levels (Ctrough) of Cetuximab
NCT03717155 (11) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (AEs), Treatment-Related Grade >=3 TEAEs and Immune-related Treatment Emergent AEs (irTEAEs)
NCT03717155 (11) [back to overview]Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
NCT03717155 (11) [back to overview]Overall Survival (OS)
NCT03717155 (11) [back to overview]Number of Participants With Positive Anti-Drug Antibody (ADA) of Cetuximab
NCT03717155 (11) [back to overview]Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab
NCT03717155 (11) [back to overview]Duration of Response (DOR)
NCT03717155 (11) [back to overview]Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
NCT03737123 (10) [back to overview]Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Carboplatin + Gemcitabine or Docetaxel
NCT03737123 (10) [back to overview]Progression Free Survival (PFS) for Atezolizumab + Carboplatin and Gemcitabine
NCT03737123 (10) [back to overview]Clinical Benefit Rate (CBR) With RECIST 1.1
NCT03737123 (10) [back to overview]Clinical Benefit Rate (CBR) With irRECIST
NCT03737123 (10) [back to overview]Overall Survival (OS)
NCT03737123 (10) [back to overview]Objective Response Rate (ORR) With irRECIST
NCT03737123 (10) [back to overview]Objective Response Rate (ORR) With RECIST 1.1
NCT03737123 (10) [back to overview]PFS by irRECIST
NCT03737123 (10) [back to overview]Progression Free Survival (PFS)
NCT03737123 (10) [back to overview]Progression Free Survival (PFS) Compared to Historical Controls
NCT03737994 (12) [back to overview]Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria
NCT03737994 (12) [back to overview]Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria
NCT03737994 (12) [back to overview]Duration of Overall Response, Per Investigator Assessment Using RECIST v1.1
NCT03737994 (12) [back to overview]Duration of Overall Response, Per Investigator Assessment Using RECIST v1.1
NCT03737994 (12) [back to overview]Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria
NCT03737994 (12) [back to overview]Overall Survival (OS)
NCT03737994 (12) [back to overview]Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria
NCT03737994 (12) [back to overview]Overall Survival (OS)
NCT03737994 (12) [back to overview]Number of Participants by Highest Grade Adverse Event Reported
NCT03737994 (12) [back to overview]Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria
NCT03737994 (12) [back to overview]Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria
NCT03737994 (12) [back to overview]Overall Survival (OS)
NCT03775486 (11) [back to overview]Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13
NCT03775486 (11) [back to overview]Concentration of Durvalumab
NCT03775486 (11) [back to overview]Duration of Response
NCT03775486 (11) [back to overview]Overall Survival
NCT03775486 (11) [back to overview]Progression-free Survival
NCT03775486 (11) [back to overview]Time to Deterioration in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13
NCT03775486 (11) [back to overview]Progression-free Survival in Homologous Recombination Repair Related Gene Mutation (HRRm) Population
NCT03775486 (11) [back to overview]Number of Participants With Treatment-Related Adverse Events
NCT03775486 (11) [back to overview]Time to Deterioration in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30
NCT03775486 (11) [back to overview]Presence of Anti-drug Antibodies (ADAs) for Durvalumab
NCT03775486 (11) [back to overview]Change From Baseline in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30
NCT03780010 (5) [back to overview]Overall RECIST 1.1 Response Rate
NCT03780010 (5) [back to overview]Median Progression Free Survival
NCT03780010 (5) [back to overview]Percent of Patients With Progression-free Survival (PFS) at 6 Months
NCT03780010 (5) [back to overview]Pharmacokinetic Profile of TRC105 When Given With Bevacizumab and Paclitaxel/Carboplatin
NCT03780010 (5) [back to overview]Treatment-Emergent Adverse Events
NCT03786783 (5) [back to overview]"Percentage of Participants Who Are Feasibility Failure"
NCT03786783 (5) [back to overview]Response Rate
NCT03786783 (5) [back to overview]Percentage of Participants With Unacceptable Toxicity
NCT03786783 (5) [back to overview]Event-free Survival
NCT03786783 (5) [back to overview]Overall Survival
NCT03830866 (6) [back to overview]Overall Survival (Duration)
NCT03830866 (6) [back to overview]Objective Response Rate (ORR)
NCT03830866 (6) [back to overview]Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression
NCT03830866 (6) [back to overview]Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression, PD-L1 Expression >= 1%
NCT03830866 (6) [back to overview]Duration of Response (DoR) in Patients With Complete Response (CR)
NCT03830866 (6) [back to overview]Complete Response Rate
NCT03840915 (7) [back to overview]Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
NCT03840915 (7) [back to overview]Overall Survival (OS)
NCT03840915 (7) [back to overview]Duration of Response (DOR)
NCT03840915 (7) [back to overview]Number of Participants With Dose-Limiting Toxicities (DLTs)
NCT03840915 (7) [back to overview]Number of Participants With Positive Antidrug Antibodies (ADA)
NCT03840915 (7) [back to overview]Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC)
NCT03840915 (7) [back to overview]Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
NCT03850444 (11) [back to overview]Number of Participants Who Experienced At Least One Adverse Event (AE)
NCT03850444 (11) [back to overview]Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
NCT03850444 (11) [back to overview]Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%
NCT03850444 (11) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
NCT03850444 (11) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
NCT03850444 (11) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
NCT03850444 (11) [back to overview]Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%
NCT03850444 (11) [back to overview]Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%
NCT03850444 (11) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%
NCT03850444 (11) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%
NCT03850444 (11) [back to overview]Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%
NCT03853707 (4) [back to overview]Clinical Benefit Rate
NCT03853707 (4) [back to overview]Overall Response
NCT03853707 (4) [back to overview]Overall Survival (OS)
NCT03853707 (4) [back to overview]Progression-free Survival (PFS)
NCT03871153 (4) [back to overview]Disease Free Survival (DFS)
NCT03871153 (4) [back to overview]Assess Adverse Events (AE)
NCT03871153 (4) [back to overview]Pathologic Complete Response Rate
NCT03871153 (4) [back to overview]Pathologic N0 Rate
NCT03875092 (6) [back to overview]Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT03875092 (6) [back to overview]Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT03875092 (6) [back to overview]Overall Survival (OS)
NCT03875092 (6) [back to overview]Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
NCT03875092 (6) [back to overview]Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
NCT03875092 (6) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT03912818 (2) [back to overview]Incidence of Grade 3-5 Adverse Events
NCT03912818 (2) [back to overview]Proportion of Subjects Who Initiate Study Treatment and Achieve Tumor Stage of pT2 N0 M0 or Better (e.g., pT0, pT1 N0) at Cystectomy
NCT03913455 (5) [back to overview]Adverse Events
NCT03913455 (5) [back to overview]Disease Control Rate (DCR)
NCT03913455 (5) [back to overview]Overall Survival (OS)
NCT03913455 (5) [back to overview]Progression Free Survival (PFS)
NCT03913455 (5) [back to overview]Objective Response Rate (ORR)
NCT03950674 (7) [back to overview]Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging
NCT03950674 (7) [back to overview]Number of Participants Who Experienced an Adverse Event (AE)
NCT03950674 (7) [back to overview]Number of Participants Who Discontinued Any Study Drug Due to an AE
NCT03950674 (7) [back to overview]Progression-Free Survival (PFS) as Assessed by Investigator Immune-related RECIST (irRECIST) Response Criteria
NCT03950674 (7) [back to overview]Overall Survival (OS)
NCT03950674 (7) [back to overview]Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
NCT03950674 (7) [back to overview]Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging
NCT03965689 (2) [back to overview]Duration of Progression Free Survival (PFS)
NCT03965689 (2) [back to overview]Overall Survival (OS)
NCT04003610 (10) [back to overview]Objective Response Rate (ORR)
NCT04003610 (10) [back to overview]EORTC QLQ-C30 Score
NCT04003610 (10) [back to overview]EORTC QLQ-C30 Score
NCT04003610 (10) [back to overview]Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score
NCT04003610 (10) [back to overview]Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score
NCT04003610 (10) [back to overview]Change From Baseline in the EORTC QLQ-C30 Score
NCT04003610 (10) [back to overview]Progression-free Survival (PFS)
NCT04003610 (10) [back to overview]Number of Participants With the Indicated EQ-5D-5L Dimension Scores
NCT04003610 (10) [back to overview]Overall Survival (OS)
NCT04003610 (10) [back to overview]Number of Participants With Treatment-emergent Adverse Events
NCT04012619 (1) [back to overview]the Maximum Tolerated Dose (MTD)
NCT04189952 (8) [back to overview]Percentage of Participants Achieving Mobilization Rate Greater Than or Equal to 2x10^6 CD34+ Cells/kg Body Weight
NCT04189952 (8) [back to overview]Percentage of Participants Achieving Overall Response
NCT04189952 (8) [back to overview]Percentage of Participants Achieving Partial Response (PR)
NCT04189952 (8) [back to overview]Number of Treatment-Emergent Adverse Events
NCT04189952 (8) [back to overview]Event-Free Survival (EFS)
NCT04189952 (8) [back to overview]Progression-Free Survival (PFS)
NCT04189952 (8) [back to overview]Overall Survival (OS)
NCT04189952 (8) [back to overview]Percentage of Participants Achieving Complete Response (CR)
NCT04631029 (4) [back to overview]Number of Participants Experiencing Grade 3 and 4 Adverse Events
NCT04631029 (4) [back to overview]Progression Free Survival (PFS) Rate
NCT04631029 (4) [back to overview]Number of Participants With Dose Limiting Toxicities
NCT04631029 (4) [back to overview]Number of Participants Who Received 3 or More Cycles of the Combination of Entinostat, Atezolizumab, Carboplatin, and Etoposide
NCT04816214 (15) [back to overview]Run-in Part: Overall Response Rate (ORR) as Per Investigator Assessment
NCT04816214 (15) [back to overview]Run-in Part: Time to Response (TTR) as Per Investigator Assessment
NCT04816214 (15) [back to overview]Run-in Part: Progression-Free Survival (PFS) as Per Investigator Assessment
NCT04816214 (15) [back to overview]Run-in Part: Duration of Response (DOR) as Per Investigator Assessment
NCT04816214 (15) [back to overview]Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)
NCT04816214 (15) [back to overview]Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Capmatinib
NCT04816214 (15) [back to overview]Run-in Part: Disease Control Rate (DCR) as Per Investigator Assessment
NCT04816214 (15) [back to overview]Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)
NCT04816214 (15) [back to overview]Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)
NCT04816214 (15) [back to overview]Run-in Part: Dose Intensity of Each Study Drug
NCT04816214 (15) [back to overview]Run-in Part: Maximum Plasma Concentration (Cmax) of Capmatinib
NCT04816214 (15) [back to overview]Run-in Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)
NCT04816214 (15) [back to overview]Run-in Part: Median Duration of Exposure to Each Study Drug
NCT04816214 (15) [back to overview]Run-in Part: Number of Participants With at Least One Dose Interruption and Dose Reduction of Each Study Drug
NCT04816214 (15) [back to overview]Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Capmatinib
NCT05718466 (3) [back to overview]Local Tumor Control
NCT05718466 (3) [back to overview]Overall Survival
NCT05718466 (3) [back to overview]Progression Free Survival

Overall Objective Response

Overall Objective Response will be assessed prior to dose-intensive therapy and at the completion of therapy. Complete disappearance of all clinical, radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy). Patients must be free of disease for a minimum of 4 weeks. Partial Response: Complete disappearance of all biochemical evidence of disease in patients without a surgical procedure for a residual radiographic mass. Patients must demonstrate no biochemical recurrence or progression of radiographic masses for a minimum of four weeks (PR to chemotherapy} (NCT00002558)
Timeframe: 2 years

,
Interventionparticipants (Number)
Complete Response (CR)Incomplete Response (IR)Partial Response (PR)
Group A50365
Group B483

[back to top]

Toxic Effects

Number of Participants with Grade 3 and 4 Adverse Events Related to Protocol-based Therapy (NCT00002931)
Timeframe: From date of randomization until death of any cause, assessed up to 12 weeks

Interventionparticipants (Number)
HyperglycemiaTransaminase aloneMucositis/stomatitisNausea/vomitingFebrile neutropeniaDiarrheaHyperbilirubinemiaFever w/o neutropeniaHypocalcemiaHemorrhageElevated INR/Prothrombin timeRenal FailureConstipationEsophagitis
HD Chemo and Auto Stem Cells461051332212111

[back to top]

Progression-free Survival

Estimated using the product-limit method of Kaplan and Meier. Progression is defined as an increase o any radiologically measureable tumor by greater than 25% or a greater than 10% increase of elevated tumor markers. (NCT00002931)
Timeframe: Until disease progression, up to 5 years.

InterventionMonths (Mean)
HD Chemo and Auto Stem Cells11.8

[back to top]

Overall Survival

Estimated using the product-limit method of Kaplan and Meier. (NCT00002931)
Timeframe: Until death from any cause, up to 5 years.

InterventionMonths (Median)
HD Chemo and Auto Stem Cells21.7

[back to top]

Objective Response

Determine the overall objective response. CR rate [as measured from the start of ICE, (or high dose CTX) to the end of transplant for those who receive it, or the end of ICE for those who do not].Complete response (CR): No evidence of Hodgkin's disease determined clinically, radiologically or pathologically when indicated (NCT00003631)
Timeframe: 2 years

,,
Interventionparticipants (Number)
FailureMinor Response (MR)Partial Response (PR)Progression Free (P-Free)Complete Response (CR)Progression of Disease (POD)
Group A - Favorable Prognostic Group3214100
Group B - Intermediate Prognostic Group6123121
Group C - Unfavorable Prognostic Group304710

[back to top]

Number of Participants With Adverse Events Grade 3 or Greater

Toxicities, Grade 3 or greater (CTC version 2.0) by treatment arm for all treated participants (NCT00003644)
Timeframe: Throughout study treatment lasting up to 24 weeks

,
InterventionParticipants (Count of Participants)
LeukopeniaThrombocytopeniaNeutropeniaAnemiaOther hematologicAllergyCardiovascularCoagulationConstitutionalDermatologicGastrointestinalGenitourinary/RenalHemorrhageHepaticInfection/FeverMetabolicMusculoskeletalPeripheral NeuropathyOther NeurologicOcular/VisualPainPulmonary
Grade 3 & Above Toxicity Paclitaxel + Carboplatin x 24 Cycles74122034781207212111151031251151
Grade 3 & Above Toxicity Paclitaxel + Carboplatin x 3 Cycles86161962477273113011150280120

[back to top]

Progression-free Survival

The percent of participants with disease recurrence within 5 years (NCT00003644)
Timeframe: Up to 5 years

Interventionpercentage of participants (Number)
Paclitaxel + Carboplatin Followed 4 Weeks Later by Paclitaxel20.4
Paclitaxel + Carboplatin Followed by Observation23.2

[back to top]

Overall Survival

Number of deaths during study and follow up. (NCT00003644)
Timeframe: up to 96 months

InterventionParticipants (Count of Participants)
Paclitaxel + Carboplatin Followed 4 Weeks Later by Paclitaxel44
Paclitaxel + Carboplatin Followed by Observation53

[back to top]

4 Year PFS

progression free survival estimate at 4 years post BMT (events are disease progression/relapse and death due to any cause) (NCT00003816)
Timeframe: 4 years

Interventionpercentage of participants (Number)
BuCy49.1
CyTBI52.2
FluMel33.2
VpCyTBI26.1
Other40

[back to top]

4 yr OS

Overall survival estimate at 4 years post BMT (NCT00003816)
Timeframe: 4-year

Interventionpercentage of participants (Number)
BuCy56.4
CyTBI56.5
FluMel38.2
VpCyTBI39.1
Other53.3

[back to top]

CR Rate

Rate of Complete Remission by Day +100 (NCT00003816)
Timeframe: day 100

InterventionParticipants (Count of Participants)
BuCy42
CyTBI55
FluMel134
VpCyTBI18
Other7

[back to top]

Toxicity/TRM at Day 100

Death due to treatment related causes before day +100 after BMT (NCT00003816)
Timeframe: Day +100

InterventionParticipants (Count of Participants)
BuCy3
CyTBI4
FluMel31
VpCyTBI4
Other4

[back to top]

Five-Year Overall Survival

Patients who were still alive were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method. (NCT00004092)
Timeframe: Five Years

Interventionpercentage of participants (Number)
Arm I (ACT)63
Arm II (STAMP V)75

[back to top]

Five-Year Relapse-free Survival

RFS events included death or disease recurrence. Patients who did not experience disease recurrence or death were censored at the date of last follow-up. Survival rates were estimates using the Kaplan-Meier method. (NCT00004092)
Timeframe: Five years

Interventionpercentage of participants (Number)
Arm I (ACT)47
Arm II (STAMP V)55

[back to top]

Overall Survival Time

Survival time is defined as time from study entry to death from any cause (NCT00004859)
Timeframe: every other month until 24 months from study entry, then every 3 months for year 3, every 4 months for year 4 and every 6 months for year 5

InterventionMonths (Median)
Arm A (Paclitaxel + Carboplatin + Radiation )15.3
Arm B (Paclitaxel + Carboplatin + Radiation + Thalidomide)16.0

[back to top]

Response Rate at Best Response to Treatment

Proportion of patients with complete or partial response using the Response Evaluation Criteria In Solid Tumors (RECIST) v1.0. Complete response is defined as the complete disappearance of all clinically detectable malignant disease for at least 4 weeks. Partial response is defined as greater than or equal to 50% decrease in tumor size for at least 4 weeks without increase in size of any area of known malignant disease of greater than 25%, or appearance of new areas of malignant disease. (NCT00004859)
Timeframe: every other month until 24 months from study entry, every 3 months for year 3, every 4 months for the 4th year and every 6 months for the 5th year

InterventionProportion of participants (Number)
Arm A (Paclitaxel + Carboplatin + Radiation )0.35
Arm B (Paclitaxel + Carboplatin + Radiation + Thalidomide)0.38

[back to top]

Time to Disease Progression

Time to disease progression is defined as the time from randomization to documented disease progression or to death without progression. Patients without documented progression or death reported were censored at the time of the last documented disease evaluation. Progression is defined, using the Response Evaluation Criteria In Solid Tumors (RECIST), as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline. (NCT00004859)
Timeframe: every other month until 24 months from study entry, every 3 months for year 3, every 4 months for the 4th year and every 6 months for the 5th year

InterventionMonths (Median)
Arm A (Paclitaxel + Carboplatin + Radiation )7.4
Arm B (Paclitaxel + Carboplatin + Radiation + Thalidomide)7.8

[back to top]

Progression-Free Survival

Progression was defined as a CA-125 value that is both twice the nadir since registration and greater than 70 units/ml, and is confirmed by a second determination at least 7 days apart, or appearance of any new lesion/site. Symptomatic deterioration was defined as a global deterioration of health status requiring removal from protocol treatment. Progression-Free Survival was defined as the time from the date of registration to the date of progression, symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at last contact date. (NCT00008138)
Timeframe: Monthly during protocol treatment, then every 3 months up to the end of Year 1, then every 6 months for the next two years, then annually up to Year 5.

Interventionmonths (Median)
Experimental: Chemo/Debulking Surgery/IP Chemo21

[back to top]

Overall Survival

Overall survival was defined as the time from the date of registration until the date of death due to any cause. Patients last known to be alive were censored at the date of last contact. Patients were followed every 3 months for the first year, every 6 months for years 2 and 3, and then annually for years 4 and 5. (NCT00008138)
Timeframe: assessed every 3 months for 1st year, then every 6 months for 2 years, then annually for years 4 and 5

Interventionmonths (Median)
Experimental: Chemo/Debulking Surgery/IP Chemo32

[back to top]

Best Overall Response by RECIST Criteria (Version 1.0)

Number of eligible, treated participants in each response category by RECIST criteria (NCT00010257)
Timeframe: Assessed every 2 cycles (6 weeks)

,
InterventionParticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressionUnevaluable
Thymic Carcinoma06842
Thymoma351302

[back to top]

Duration of Response

Time from first satisfaction of response criteria to onset of disease progression, assessed using RECIST criteria (NCT00010257)
Timeframe: assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter

InterventionMonths (Median)
Thymoma16.9
Thymic Carcinoma5.0

[back to top]

Number of Participants With Observed Adverse Effects (Grade 3 and Above) Assessed by Common Toxicity Criteria Version 2.0

(NCT00011986)
Timeframe: Up to 9 years

,,,,
InterventionParticipants (Count of Participants)
LeukopeniaNeutropeniaThrombocytopeniaAnemiaOther HematologicAllergyAuditoryCardiovascularCoagulationConstitutionalDermatologicEndocrineGastrointestinalGenitourinary/RenalHemorrhageHepaticInfection/FeverMetabolicMusculoskeletalNeurologicPeripheral NeurologicOcular/VisualPainPulmonarySexualSecond Primary
Grade 3 and Above on Carbo/Gemcitabine - Carbo/Taxol51376148620331526123757819293025824510352435237057
Grade 3 and Above on Carbo/Taxol/Doxil595782320160244283344841121241320111345513434517539151
Grade 3 and Above on Carbo/Taxol/Gemcitabine68679852019633820236109664145829321385518475937537066
Grade 3 and Above on Carbo/Topotecan - Carbo/Taxol4767793031672462121797361105681384378283536621141
Grade 3 and Above on ToxicityCarbo/Taxol4387491931021563852055413090981376617344515319034

[back to top]

Progression-free Survival

Median duration in months of progression free survival. (NCT00011986)
Timeframe: From the date of enrollment to first progression or death or last contact, if alive and progression free.

Interventionmonths (Median)
Carbo/Taxol16.0
Carbo/Taxol/Gemcitabine16.3
Carbo/Taxol/Doxil16.4
Carbo/Topotecan - Carbo/Taxol15.4
Carbo/Gemcitabine - Carbo/Taxol15.4

[back to top]

Overall Survival

Proportion of participants whose overall survival exceeded 5 years. (NCT00011986)
Timeframe: Up to 9 years

InterventionProportion of participants (Number)
Carbo/Taxol0.35
Carbo/Taxol/Gemcitabine0.34
Carbo/Taxol/Doxil0.39
Carbo/Topotecan - Carbo/Taxol0.34
Carbo/Gemcitabine - Carbo/Taxol0.30

[back to top]

Toxicity

Patients were evaluated for acute toxicities defined as grade 3 or greater cardiovascular (including venous thrombosis), gastrointestinal, or genitourinary toxicity occurring during the period starting from treatment initiation until 90 days or less after the completion of radiotherapy. The same toxicity measures were monitored at >90 days after the completion of radiotherapy. (NCT00016913)
Timeframe: 90 days and 1 year post treatment

InterventionEvents (Number)
Grade 3+ Toxicity <=90 days post radiotherapyGrade 3+ Toxicity >90 days post radiotherapy
Neo-Adj ChemoTx + Ablation Prior to RT20

[back to top]

Time to Prostate-specific Antigen Failure

PSA progression was defined in 2 ways. The CALGB PSA progression was defined as 2 consecutive rises in PSA with a rise of at least 0.2 ng/mL and above 1.0 ng/mL after radiation therapy; the date of PSA failure is taken as the midpoint between the last PSA before the rise and the first of the 2 PSAs that documented the rise. In addition, PSA progression was used according to the American Society for Therapeutic Radiology and Oncology 1996 (ASTRO) criteria and defined as 3 consecutive rises in PSA after radiation therapy. The date of PSA failure was taken as the midpoint between the time of the lowest PSA measure after irradiation and the first of the 3 consecutive rises. (NCT00016913)
Timeframe: PSA was measured every 4 weeks during chemotherapy, at least every 12 weeks post radiation for 2 years, and every 6 months thereafter until PSA failure date (Up to 5.5 years).

Interventionmonths (Median)
CALGB criteriaASTRO criteria
Neo-Adj ChemoTx + Ablation Prior to RT17.112.1

[back to top]

Progression-free Survival (PFS)

PFS was defined as the time between treatment initiation and the date of disease progression (PSA, bone, tumor) or death, whichever occurred first. PSA progression is defined as 2 consecutive rising PSAs (a rise of at least 0.2 ng/mL) above 1.0 ng/mL. (NCT00016913)
Timeframe: registration to progression, up to 5.5 years from registration

Interventionmonths (Median)
Neo-Adj ChemoTx + Ablation Prior to RT12.1

[back to top]

Overall Survival- Percentage of Participants Who Survived at 10 Years

Overall survival of the participants was measured from the date of randomization up to the date of death due to any cause. Overall survival was estimated using the Kaplan-Meier method. (NCT00021255)
Timeframe: From randomization until death or up to 10 years

Interventionpercentage of particpants (Number)
Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T)78.9
AC Followed by Docetaxel + Herceptin (AC→TH)86.0
Docetaxel + Carboplatin + Herceptin (TCH)83.4

[back to top]

Percentage of Participants With Disease Free Survival at 10 Years

Disease free survival was defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix) or death from any cause whichever occured first. Disease free survival was estimated using the Kaplan-Meier method. (NCT00021255)
Timeframe: From randomization until relapse or death or up to 10 years

Interventionpercentage of participants (Number)
Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T)67.2
AC Followed by Docetaxel + Herceptin (AC→TH)73.4
Docetaxel + Carboplatin + Herceptin (TCH)72.3

[back to top]

Percentage of Participants With Disease Free Survival at 5 Years

Disease Free Survival was defined as the interval from the date of randomization to the date of local, regional or metastatic relapse or the date of second primary cancer (with the exception of curatively treated non-melanoma skin cancer or in situ carcinoma of the cervix) or death from any cause whichever occured first. Disease free survival was estimated using the Kaplan-Meier method. (NCT00021255)
Timeframe: From randomization until relapse or death or up to 5 years

Interventionpercentage of participants (Number)
Doxorubicin+Cyclophosphamide (AC) Followed by Docetaxel (AC→T)75.5
AC Followed by Docetaxel + Herceptin (AC→TH)83.2
Docetaxel + Carboplatin + Herceptin (TCH)81.0

[back to top]

Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level)

Percent volume of total lung receiving > 20 Gy radiation therapy (Lung V20) was compared between the two patient groups of those who experienced a grade 3 and higher lung toxicity and those who did not. Similarly, it was also compared between the two patient groups of those who experienced a grade 2 and higher esophageal toxicity and those who did not. Toxicities graded using CTC v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. (NCT00023673)
Timeframe: From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)

,
InterventionPercent (V20) (Median)
Lung Toxicity: Lung V20Esophagitis Toxicity: Lung V20
High Grade Toxicity26.326.3
No High Grade Toxicity24.122.4

[back to top]

Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy

"Dose limiting toxicity (DLT) = Grade 3/4 non-hematologic toxicities (excluding nausea, vomiting, and alopecia) and Grade 4 hematologic toxicities. The DLT rate for this study was set at 40% based on Radiation Therapy Oncology Group (RTOG) study 94-10. No acute (within 90 days from start of 3DRT) DLT's in the first 5 patients (0/5) or the combination of one acute DLT in the first 5 patients (1/5) and none in the next 2 patients (0/2) was required to deem a given dose level to be acceptable. If at any time a Grade 5 toxicity (death) occurred, accrual would be suspended and the event reviewed by a study chair. At any given dose level, this design gives at least 90% confidence that the true acute DLT rate is less than 40% and the probability of not escalating when the true toxicity rate is 40% or higher is at least 83%.~Rating scale: 0 = not the MTD, 1 = MTD" (NCT00023673)
Timeframe: From start of treatment to 90 days

Interventionunits on a scale (Number)
Phase I: 75.25 Gy/36 fx + Chemotherapy0
Phase I: 74 Gy/37 fx + Chemotherapy1

[back to top]

Number of Patients With Complete Response at 3 Months After Completion of Therapy

"Complete response means no evidence of tumor on the CT scan." (NCT00023673)
Timeframe: From start of treatment until 3 months after completion of all study treatment, estimated to be 5 or 6.5 months depending whether or not subject received optional adjuvant chemotherapy.

InterventionParticipants (Count of Participants)
Phase I/II: 74 Gy/37 fx + Chemotherapy3

[back to top]

Percentage of Patients Who Survive at Least 12 Months

Null hypothesis: p<= 62.3% (the best arm of RTOG 94-10); alternative hypothesis: p>= 77.9%. Where p is the percentage of patients alive at at 12 months. Using a one-group chi-square test with alpha = 0.10, a sample size of 50 patients provides at least 87% power to detect a 25% or greater relative increase in the 12-month survival rate, or equivalently, an absolute increase of at least 15.6 percentage points (62.3 versus 77.9). If the point estimate is greater than 71.1% (upper bound), then the conclusion is that the 12-month survival rate from the new treatment significantly improved from 62.3%. (NCT00023673)
Timeframe: From registration to 1 year

Interventionpercentage of participants (Number)
Phase I/II: 74 Gy/37 fx + Chemotherapy75.5

[back to top]

Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities.

Highest grade toxicity per subject was counted. Toxicities were graded using the Common Toxicity Criteria (CTC) v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.Chemotherapy/Acute RT toxicities occur during chemotherapy and/or within 90 days of the start of RT. Late RT toxicities occur more than 90 days after the start of RT. (NCT00023673)
Timeframe: Chemotherapy/Acute RT toxicity: from start of treatment to 90 days from start of study treatment; Late RT toxicity: from 90 days after start of treatment to last follow-up (Maximum follow-up = 57.9 months.)

InterventionParticipants (Count of Participants)
Chemotherapy/Acute RT non-hematologic: Grade 1Chemotherapy/Acute RT non-hematologic: Grade 2Chemotherapy/Acute RT non-hematologic: Grade 3Chemotherapy/Acute RT non-hematologic: Grade 4Chemotherapy/Acute RT non-hematologic: Grade 5Chemotherapy/Acute RT hematologic: Grade 1Chemotherapy/Acute RT hematologic: Grade 2Chemotherapy/Acute RT hematologic: Grade 3Chemotherapy/Acute RT hematologic: Grade 4Chemotherapy/Acute RT hematologic: Grade 5Late RT toxicity: Grade 1Late RT toxicity: Grade 2Late RT toxicity: Grade 3Late RT toxicity: Grade 4Late RT toxicity: Grade 5
Phase I/II: 74 Gy/37 fx + Chemotherapy41628221837521310911

[back to top]

Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level)

Mean lung dose was compared between the two patient groups of those who experienced a grade 3 and higher lung toxicity and those who did not. Similarly, mean lung dose, and mean esophageal dose were compared between the two patient groups of those who experienced a grade 2 and higher esophageal toxicity and those who did not. Toxicities graded using CTC v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity. (NCT00023673)
Timeframe: From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)

,
InterventionGy (mean dose) (Mean)
Lung Toxicity: Mean Lung DoseEsophagitis Toxicity: Mean Lung DoseEsophagitis Toxicity: Mean Esophageal Dose
High Grade Toxicity17.216.924.6
No High Grade Toxicity15.214.521.0

[back to top]

Event-free Survival

Event-free survival is calculated from the date of study enrollment to the date of disease progression, disease relapse, occurrence of second neoplasm, or death from any cause. The product-limit (Kaplan-Meier) estimate is for estimation of Event -free survival (EFS) probability at 5 years. (NCT00027846)
Timeframe: Up to 5 years after completion of study treatment

InterventionProbability of EFS at 5 years (Number)
GTR1 Differentiated Histology Supratentorial (Group 1)0.614
Radiation (Group 2)0.685
Sub-Total Resection Any Histology or Location (STR) (Group 3)0.372

[back to top]

Event-free Survival (EFS)

EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who had sub-total resection initially. The event-free survival (EFS) defined as the date of disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start date of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability. (NCT00027846)
Timeframe: At 5 years since the time of radiation therapy.

InterventionProbability of EFS at 5 years (Number)
Differentiated Ependymoma0.424
Anaplastic Ependymoma0.298

[back to top]

Event-free Survival (EFS)

EFS between centrally reviewed differentiated ependymoma and anaplastic ependymoma for the patients who were treated with radiation therapy only. The event-free survival (EFS) defined as the time to disease progression, disease relapse, occurrence of a second neoplasm, or death from any cause, measured from the start of radiation therapy. The product-limit (Kaplan-Meier) estimate is for estimation of EFS probability at 5 years. (NCT00027846)
Timeframe: At 5 years since the time of radiation therapy

InterventionProbability of EFS at 5 years (Number)
Differentiated Ependymoma0.746
Anaplastic Ependymoma0.607

[back to top]

Overall Survival

Overall survival (OS) is measured from the date of study enrollment to the date to death. The product-limit (Kaplan-Meier) estimate is for estimation of OS probability at 5 years. (NCT00027846)
Timeframe: Up to 5 years after completion of study treatment

InterventionProbability of OS at 5 years (Number)
GTR1 Differentiated Histology Supratentorial (Group 1)1
Radiation (Group 2)0.862
Sub-Total Resection Any Histology or Location (STR) (Group 3)0.702

[back to top]

Rate of Gross-total or Near-total Resection and Second Surgery After Chemotherapy

The Rate Of Gross-Total or Near-Total Resection With Second Surgery After Chemotherapy Treatment. (NCT00027846)
Timeframe: At the time of second surgery

Interventionpercentage of participants (Number)
Sub-Total Resection Any Histology or Location (STR) (Group 3)76

[back to top]

Local Control and Patterns of Failure

Documented and analyzed qualitatively and quantitatively. (NCT00027846)
Timeframe: Up to 5 years after completion of study treatment

,,
InterventionParticipant (Number)
Local controlPattern of failure localPattern of failure MetastaticPattern of failure local & metastatic
GTR1 Differentiated Histology Supratentorial (Group 1)6401
Radiation (Group 2)21757267
Sub-Total Resection Any Histology or Location (STR) (Group 3)293154

[back to top]

Progression Free Survival

Kaplan-Meier estimates will be used to verify the progression free survival. (NCT00039195)
Timeframe: 2 years

Interventionpercentage of patients progression free (Number)
Induction R-CHOPac Therapy79

[back to top]

Complete Resection Rates

(NCT00043108)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
TreatmentNA

[back to top]

Event-free Survival

(NCT00043108)
Timeframe: 5 years

Interventionmonths (Median)
TreatmentNA

[back to top]

Pathologic Complete Remission (pCR)

(NCT00043108)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
TreatmentNA

[back to top]

Survival

(NCT00043108)
Timeframe: 5 years

Interventionmonths (Median)
TreatmentNA

[back to top]

Toxic Death Rate

(NCT00043108)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
TreatmentNA

[back to top] [back to top]

Pathologic Complete Response Rate by Transurethral Resection of Bladder Tumor (TURBT) and Imaging Studies After Chemotherapy

Pathologic complete response (CR) is defined as absence of viable tumor in the TURBT specimen. Stable/No Response is defined as at least some disease evaluation tests were done (same tests as baseline) and status does not qualify for CR or Progression. Progression is defined as one or more of the following must occur: unequivocal progression of disease in the opinion of the treating physician. Appearance of any new lesion/site. Death due to disease without documented progression or symptomatic deterioration. (NCT00045630)
Timeframe: up to 12 weeks after registration (assessed within 8 weeks after completion of 3 cycles of chemotherapy )

Interventionpercentage of participants (Number)
Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery46

[back to top]

Overall Survival (OS)

Overall survival is defined from the date of registration to date of death from any cause (NCT00045630)
Timeframe: 0-2 years

Interventionpercentage of participants (Number)
Gemcitabine, Paclitaxel, Carboplatin Followed by Surgery59

[back to top]

Overall Survival (OS)

Overall Survival was defined as time from study entry to death from any cause. Overall survival was estimated by KM estimate. (NCT00047320)
Timeframe: At 3 years from study entry

InterventionProbability (Number)
Radiation Therapy (CR From Induction)0.927

[back to top]

The Probability of Event-free Survival (EFS)

Event-free Survival was defined as time from study entry to death from any cause, disease progression or recurrence, or second malignant neoplasm. Event-free survival was estimated by KM estimate. (NCT00047320)
Timeframe: At 3 years from study entry

InterventionProbability (Number)
Radiation Therapy (CR From Induction)0.837

[back to top]

Progression-free Survival (PFS)

Progression-free Survival was defined as time from study entry to disease progression or recurrence. Deaths that are clearly unrelated to disease progression, and second neoplasms are censored in this analysis. Progression -free survival was estimated by KM estimate. (NCT00047320)
Timeframe: At 3 years from study entry

InterventionProbability (Number)
Radiation Therapy (CR From Induction)0.837

[back to top]

Occurrence of Non-hematological Grade 4 Toxicity Occurrence of Nonhematological Grade 4 Toxicity

The number of patients who experienced non-hematological grade 4 toxicities anytime during chemotherapy. (NCT00047320)
Timeframe: During chemotherapy(up to 18 weeks)

Interventionparticipants (Number)
Radiation Therapy (CR From Induction)22

[back to top]

Number of Patients Experiencing Toxic Death

Toxic death, defined as death predominantly attributable to treatment-related causes. (NCT00047320)
Timeframe: During chemotherapy (up to 18 weeks)

InterventionParticipants (Count of Participants)
Radiation Therapy (CR From Induction)0

[back to top]

Response to Induction Chemotherapy

A patient who achieves a complete or partial response, defined a reduction of at least 65% in tumor size after induction chemotherapy will be considered to have experienced response. (NCT00047320)
Timeframe: 18 weeks

InterventionParticipants (Count of Participants)
ResponderNon-Responder
Radiation Therapy (CR From Induction)7411

[back to top]

Objective Response Rate

Complete response:Complete disappearance of all clinically detectable malignant disease for at least 4 weeks.Partial Response:Definite improvement in evaluable disease estimated to be in excess of 50% and agreed upon by 2 investigators. Response must last for at least 4 weeks.Stable disease:No significant change in disease for at least 4 weeks. Includes an estimated decrease of <50% and lesions with an estimated increase of <25%.Progressive disease(PD):Definite increase in area of any malignant lesion estimated to be >=25% or appearance of new lesions. Need for radiotherapy is considered PD. (NCT00049257)
Timeframe: Evaluated every 12 weeks during Treatment Period

Interventionparticipants (Number)
Participants with Complete ResponseParticipants with Partial ResponseParticipants with Stable DiseaseParticipants with Progression of Disease
Carboplatin, Paclitaxel112337

[back to top]

Overall Survival Rate

Complete response:Complete disappearance of all clinically detectable malignant disease for at least 4 weeks.Partial Response:Definite improvement in evaluable disease estimated to be in excess of 50% and agreed upon by 2 investigators. Response must last for at least 4 weeks.Stable disease:No significant change in disease for at least 4 weeks. Includes an estimated decrease of <50% and lesions with an estimated increase of <25%.Progressive disease(PD):Definite increase in area of any malignant lesion estimated to be >=25% or appearance of new lesions. Need for radiotherapy is considered PD. (NCT00049257)
Timeframe: Assessed every two months after completion of study treatment for 4 years

Interventionparticipants (Number)
DeceasedAliveLost to Follow-upWithdrawal by subject
Carboplatin, Paclitaxel461110

[back to top]

Prostate-specific Antigen (PSA) Response Rate

PSA response is defined as a decline from the baseline value of >=50% confirmed by a second PSA value 4 or more weeks later. (NCT00049257)
Timeframe: Evaluated every 28 days during Treatment Period. Number of completed cycles among 58 treated patients range from 1 to 24 cycles with a median of 4.5 cycles. one cycle = 28 days.

Interventionparticipants (Number)
Participants with PSA responseParticipants with no PSA response
Carboplatin, Paclitaxel2830

[back to top]

Time to PSA Progression

In patients whose PSA has not decreased, progressive disease is a 25% increase over the baseline value and an increase in the absolute value PSA level by >=5ng/ml, confirmed by a second value at >=4 week intervals. In patients whose PSA has decreased but has not reached response criteria, progressive disease is defined as an increase in PSA by 25% over the nadir, provided that the increase is >=5ng/ml and is confirmed by a second value at >=4 week intervals. (NCT00049257)
Timeframe: Evaluated every 28 days during Treatment Period

Interventiondays (Median)
Carboplatin, Paclitaxel115

[back to top]

Overall Survival

(NCT00050960)
Timeframe: From date of randomization to date of death

InterventionMonths (Median)
Bexarotene With Carboplatin and Paclitaxel8.5
Carboplatin and Paclitaxel9.2

[back to top]

To Measure EGFR Gene Amplification in Tumor Specimens

(NCT00059787)
Timeframe: The duration of the study for up to 7 years

Interventionnumber of tumor specimens (Number)
No amplificationLow-level amplificationmoderate high amplification
Paclitaxel, Carboplatin, Erlotinib1163

[back to top]

Pathologic Complete Response Rates

Pathologic complete response was defined as having no pathologic or cytologic evidence of disease following surgical reassessment. (NCT00059787)
Timeframe: Up to 7 years

Interventionparticipants (Number)
Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)8

[back to top]

To Determine Progession Free Survival With the Addition of OSI-774 (Tarceva) to the Combination of Paclitaxel and Carboplatin

(NCT00059787)
Timeframe: The duration of the study

Interventionmonths (Median)
Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)34.3

[back to top]

The Percentage of Participants Experiencing Toxicty (Grade 2 and Grade 3/4) Associated With the Combined Regimen

Adverse event assessment (NCT00059787)
Timeframe: For the duration of the study up to 7 years

Interventionpercentage of participants (Number)
Grade 3-4 neutropeniaGrade 3-4 skin rashGrade 3-4 thrombocytopeniaGrade 3-4 infectionGrade 3-4 fatigueGrade 3 diarrheaGrade 2 skin rashGrade 2 diarrhea
Paclitaxel, Carboplatin, Erlotinib18177754217

[back to top]

To Determine the Tolerability of Twelve Months of Maintenance Treatment

(NCT00059787)
Timeframe: Twelve months of maintenance

Interventionparticipants (Number)
No recurrenceRecurrence
Treatment (Paclitaxel, Carboplatin, Erlotinib Hydrochloride)124

[back to top]

Number of Patients With Response

Response defined by tumor assessment using Response Evaluation Criteria In Solid Tumors (RECIST) to learn effectiveness of Tarceva (OSI-774) when combined with standard chemotherapy before surgery. (NCT00063258)
Timeframe: 5 Years to collect outcome information

InterventionParticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive Disease
Chemotherapy + Tarceva0010

[back to top]

Number of Participants With Indicated Severity of CTCAE v2 Graded Neurotoxicity and Infection

Maximum grade of physician assessed neurotoxicity and infection (NCT00063999)
Timeframe: Assessed throughout the treatment period and for 30 days after discontinuation of treatment.

,
InterventionParticipants (Count of Participants)
Grade < 2 Sensory neuropathyGrade 2 or Higher Sensory NeuropathyGrade <3 infection with NeutropeGrade 3 or Higher Infection with NeutropeniaGrade <3 infection without NeutropeniaGrade 3 or Higher Infection without Neutropenia
Arm I (Doxorubicin Hydrochloride, Cisplatin, Paclitaxel)1674732561522618
Arm II (Paclitaxel, Carboplatin)1305342963513651

[back to top]

Patient-reported Neurotoxicity (Ntx) as Measured by the FACT/GOG-Ntx Subscale (Short)

The FACT/GOG-Ntx subscale (short version) contains 4 items measuring sensory neuropathy. Each item is scored using a 5-point Likert scale (0=not at all; 1= a little bit; 2=somewhat; 3=quite a bit; 4=very much). For east item, reversal was performed prior to score calculation so that a large score suggests less symptom. according to the FACIT measurement system, the subscale score was calculated as the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The Ntx subscale score ranges 0-16 with a large subscale score suggests less symptom or better QOL (Quality of Life). (NCT00063999)
Timeframe: Baseline, 6 weeks post treatment start, 15 weeks post treatment start and 26 weeks post treatment start

,
Interventionunits on a scale (Least Squares Mean)
Baseline6 Weeks15 Weeks26 Weeks
Doxorubicin, Cisplatin, Paclitaxel14.913.511.19.5
Paclitaxel, Carboplatin14.911.311.210.9

[back to top]

Patient Reported Quality of Life as Measured With the Combination of Physical Well-being (PWB) Subscale and Functional Well-being (FWB) Subscale From the FACT-G

The FACT-G contains 4 subscales: Physical Well Being (7 items), Social Well Being (7 items), Emotional Well Being (6 items), Functional Well Being (7 items). The combination (14 items) of the physical well-being (PWB) and functional well-being (FWB) subscales was used to measure the HRQOL (Health Related Quality of Life). Each item is scored using a 5-point Likert scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). for each negative item, reversal was performed prior to score calculation so that a large score suggests better QOL. A subscale score was calculated as the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answred item scores by the number of items in the subscale. The QOL was measured with the summation of the PWB and FWBsubscale score and ranges 0-56 with a large score suggests better QOL. (NCT00063999)
Timeframe: Pre-treatment, 6 weeks post starting treatment (prior to cycle 3), 15 weeks post starting treatment (prior to cycle 6), 26 weeks post starting treatment

,
Interventionunits on a scale (Least Squares Mean)
Baseline6 weeks15 weeks26 weeks
Arm I (Doxorubicin, Cisplatin, Paclitaxel)39.435.535.339.8
Arm II (Paclitaxel, Carboplatin)37.937.536.538.5

[back to top]

Pathologic Nodal Status

According to Primary Tumor Response Pathologic lymph node status N0 Axillary and other nearby lymph nodes do not have cancer (when looked at under a microscope) N1 Micrometastases (very small clusters of cancer) OR 1-3 axillary lymph nodes have cancer AND/OR Internal mammary nodes have tiny amounts of cancer found on sentinel node biopsy N2 4-9 axillary lymph nodes have cancer OR Internal mammary nodes have cancer, but axillary lymph nodes do not have cancer N3 10 or more axillary lymph nodes have cancer OR Infraclavicular (under the clavicle) nodes have cancer OR Internal mammary nodes have cancer plus 1 or more axillary lymph nodes have cancer OR 4 or more axillary lymph nodes have cancer plus internal mammary nodes have cancer or micrometastases found on sentinel node biopsy OR Supraclavicular (above the clavicle) nodes have cancer (NCT00068341)
Timeframe: 5 years

,,
Interventionparticipants (Number)
N(0)N+
Arm I (Pre-op TCH)96
Her2- (Pre-op TC)2123
Her2+ (Pre-op TC, Post-op Herceptin)411

[back to top]

Tumor Response Assessment

Measured by physical examination compared to breast mammography and MRI assessment (NCT00068341)
Timeframe: 5 years

Interventionparticipants (Number)
Arm I: Her2 +6
Arm II: Her2 +1
Arm III: Her -12

[back to top]

Clinical Tumor Response by Physical Exam and Imaging Studies

(NCT00068341)
Timeframe: 5 years

,,
Interventionparticipants (Number)
Complete ResponsePartial ResponseMarginal Response
Arm I: Her2+870
Arm II:Her2+571
Arm III: Her2-18214

[back to top]

Clinico-histologic Predictors of pCR (Pathologic Complete Response)

(NCT00068341)
Timeframe: 5 years

,
Interventionparticipants (Number)
ER-negativeER-positivePR-negativePR-positiveER and PR both negativeER and PR one negativeER and PR both positiveHER2 negativeHER2 positiveT-Stage T2T-Stage T3T-Stage T4Tumor Type - IDC onlyTumor Type - all others (compared to IDC only)Tumor Type - ILC onlyTumor Type - all other comparted to (ICL only)Triple Negative-yesTriple Negative-noFISH positive Herceptin NoFISH positive Herceptin Yes
Pathologic CR - No143824281410283022927163814943538139
Pathologic CR - Yes11814597312751311900196716

[back to top]

Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively.

"Objective response rate of patients treated with Taxotere/carboplatin with or without Herceptin preoperatively. Objective response equals the combination of complete response (CR), partial response (PR) and marginal response (MR).~Tumor size was assessed by (1) physical examination, (2) mammography and (3) MRI. 5 response groups: complete response (CR), partial response (PR), marginal response (MR), stable disease (SD) & disease progression (DP). Pathologic response assigned into 2 groups: pCR and non-pCR. pCR-no evidence of residual invasive disease in specimen." (NCT00068341)
Timeframe: 5 years

,,,
Interventionparticipants (Number)
DFS (Disease Free Survival)OS (overall survival)
Arm I: HER2+1313
Arm II: HER2+811
HER2-3339
Total5463

[back to top]

Group C Eyes - Treatment Failure Within One Year

"Each Group C eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the Mean measure type." (NCT00072384)
Timeframe: One year

InterventionProbability of treatment failure (Mean)
Treatment (Chemotherapy, Surgery)0.25

[back to top]

Group D Eyes - Treatment Failure Within One Year

"Each Group D eye will be classified as experiencing failure within one year after start of treatment: yes or no. The method of Rosner et al. (Biometrics v. 38, 105-114, 1982) will be used to model possible dependence between eyes from the same patient. The point estimate of the probability of treatment failure is reported as the Mean measure type." (NCT00072384)
Timeframe: One year

InterventionProbability of treatment failure (Mean)
Treatment (Chemotherapy, Surgery)0.52

[back to top]

Event-free Survival (EFS)

Proportion of patients event free at 1 year following enrollment. Event free survival time is computed as the time to study entry until disease relapse/progression, secondary malignancy, or death. (NCT00072384)
Timeframe: One year after study enrollment

InterventionPercentage probability (Number)
Treatment (Chemotherapy, Surgery)45.45

[back to top]

Patterns of Treatment Failure vs. no Treatment Failure for Group C Eyes and Group D Eyes According to Initial Sites of Involvement

The association between the probability of experiencing treatment failure vs. no failure in a C eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia. The association between the probability of experiencing treatment failure vs. no failure in a D eye and the presence of subretinal seeding (SRS), subretinal fluid (SRF), or vitreal seeding (VS) at the on study ophthalmological examination under anesthesia. (NCT00072384)
Timeframe: From the date of enrollment assessed up to 12 months

,
InterventionEyes (Number)
Treatment failure- SRS, SRF, VSTreatment failure- SRS; no SRF; no VSTreatment failure- SRS and SRF; no VSTreatment failure- SRS and VS; no SRFTreatment failure- SRF; no SRS; no VSTreatment failure- SRF and VS; no SRSTreatment failure- VS; no SRS; no SRFTreatment failure- No SRS; no VS; no SRFNo treatment failure- SRS, SRF, VSNo treatment failure- SRS; no SRF; no VSNo treatment failure- SRS and SRF; no VSNo treatment failure- SRS and VS; no SRFNo treatment failure- SRF; no SRS; no VSNo treatment failure- SRF and VS; no SRSNo treatment failure- VS; no SRS; no SRFNo treatment failure- No SRS; no VS; no SRF
Group C Eyes0000100000001011
Group D Eyes3030232021222021

[back to top]

Patterns of Failure for Group C and Group D in Terms of Vitreous vs Patterns of Failure for Group C and Group D in Terms of Vitreous vs Retinal vs Both as Sites of Recurrence

Sites of disease recurrence for Group C and Group D eyes where treatment failure was detected (NCT00072384)
Timeframe: From the date of enrollment assessed up to 36 months

,
InterventionEyes (Number)
Retinal seeding and vitreal seedingRetinal seeding but no vitreal seedingVitreal seeding but no retinal seedingNeither retinal seeding nor vitreal seeding
Group C Eyes0100
Group D Eyes1714

[back to top]

Toxicity Associated With Chemotherapy

The number of patients that experience CTC Version 4 grade 3 or higher toxicities of any kind. (NCT00072384)
Timeframe: From date of enrollment until termination of protocol therapy assessed up to 72 weeks

InterventionPatients (Number)
Treatment (Chemotherapy, Surgery)10

[back to top]

Peripheral Blood Stem Cell Collection

Count of patients that attempted and had successful autologous peripheral blood stem cell (PBSC) collection. (NCT00072514)
Timeframe: Up to 12 weeks

InterventionParticipants (Count of Participants)
Attempted PBSC CollectionSuccessful PBSC Collection
Treatment1717

[back to top]

Overall and Complete Response Rates

Response was assessed per standard criteria (Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria fornon-Hodgkin's lymphomas. J Clin Oncol 1999;17:1244-1253.) (NCT00072514)
Timeframe: 3-4 weeks after completion of study treatment

Interventionpercentage of participants (Number)
OverallComplete
Treatment6731

[back to top]

Hematologic and Non-hematologic Adverse Events.

Count of participants with grade 3/4 hematologic and non-hematologic adverse events. (NCT00072514)
Timeframe: 3-4 weeks after completion of study treatment

InterventionParticipants (Count of Participants)
Hematologic Grade 3Hematologic Grade 4Non-Hematologic Grade 3Non-Hematologic Grade 4
Treatment1039232

[back to top]

Ability to Successfully Deliver the Investigational Therapy Without Incurring the Protocol Suspension Rules

Count of participants that received the investigational therapy without incurring the protocol suspension rules. A stopping rule for safety was employed such that the study would be suspended if sufficient evidence indicated that the true grade 4-5 non-hematologic toxicity rate exceeded 10%. (NCT00072514)
Timeframe: At 3-4 weeks after completion of study treatment

InterventionParticipants (Count of Participants)
Treatment51

[back to top]

Number of Participants With a Complete Response Rate to Chemotherapy Regimen Assessed by Radiographic Response at 2 Years.

Per RECIST criteria (v1.1) and assessed by magnetic resonance imaging (MRI): Complete response (CR), Disappearance of all target lesions. (NCT00074165)
Timeframe: 2 years

InterventionParticipants (Number)
Rituximab and Carboplatin1

[back to top]

Number of Participants Who Experienced Toxic Death

Primary safety endpoints are (1) the occurrence of toxic death, which is death during treatment that is not primarily attributable to disease progression, and (2) the occurrence of grade 4 allergy to carboplatin. (NCT00077207)
Timeframe: Up to 6 years after the start of protocol therapy

InterventionParticipants (Count of Participants)
Carboplatin, Vincristine Sulfate, Temozolomide)0

[back to top]

Number of Participants Who Experienced a Grade 3 or 4 Thrombocytopenia and/or Neutropenia.

Occurence of grade 3 or 4 thrombocytopenia or neutropenia while receiving protocol therapy. (NCT00077207)
Timeframe: Up to 18 months of protocol therapy

InterventionParticipants (Count of Participants)
Carboplatin, Vincristine Sulfate, Temozolomide)43

[back to top]

Long Term Feasibility Success

"Success is defined as the completion of induction plus four cycles of maintenance within 60 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage.~If the participant completes all therapy within 60 weeks the patient is a long-term feasibility success. As such, a patient who experiences short term feasibility failure can be classified as a long-term feasibility success." (NCT00077207)
Timeframe: 60 weeks

Interventionparticipants (Number)
Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)41

[back to top]

Short Term Feasibility Success

"Success is defined as the completion of induction plus one cycle of maintenance within 24 weeks of enrollment without more than a 25% reduction in either carboplatin or temozolomide dosage.~Failure to complete the induction and one cycle of maintenance within 24 weeks counts as a short-term-feasibility failure." (NCT00077207)
Timeframe: 24 weeks

Interventionparticipants (Number)
Treatment (Carboplatin, Vincristine Sulfate, Temozolomide)25

[back to top]

Percentage Probability of Event-free Survival (EFS)

Percentage probability of being alive and without the occurrence of disease progression or second malignant neoplasm 6 years following enrollment. (NCT00077207)
Timeframe: Six years

Interventionpercent probability EFS (Number)
Carboplatin, Vincristine Sulfate, Temozolomide)40.89

[back to top]

Percent Probability of Progression-free Survival (PFS)

Percentage probability of being alive and without the occurrence of disease progression 3 years following enrollment. (NCT00077207)
Timeframe: 3 years

InterventionPercent probability PFS (Number)
Carboplatin, Vincristine Sulfate, Temozolomide)60.59

[back to top]

Time to Disease Progression for HER2+ Patients

This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored. (NCT00077376)
Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

InterventionMonths (Median)
Trastuzumab/Ixabepilone/Carboplatin7.1

[back to top]

Time to Treatment Failure for All Treated Patients

Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment. (NCT00077376)
Timeframe: Assessed every cycle until treatment discontinuation

InterventionMonths (Median)
Trastuzumab/Ixabepilone/Carboplatin5.9

[back to top]

Objective Response for HER2+ Patients (Best Objective Response a Patient Has Ever Experienced on Study)

"To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up.~The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks." (NCT00077376)
Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

InterventionParticipants (Number)
Complete ResponsePartial ResponseNo Change/ StableProgressionUnevaluable
Trastuzumab/Ixabepilone/Carboplatin31310112

[back to top]

Time to Treatment Failure for HER2+ Patients

Time from study entry to the date at which a patient was removed from treatment due to progression, toxicity, refusal or death. If a patient was considered to be a major treatment violation or was taken off study as a non-protocol failure, the patient would be censored on the date he/she was removed from treatment. (NCT00077376)
Timeframe: Assessed every cycle until treatment discontinuation

InterventionMonths (Median)
Trastuzumab/Ixabepilone/Carboplatin5.4

[back to top]

Objective Response for All Treated Patients (the Best Response a Patient Has Ever Experienced on Study)

"To assess objective response, it is necessary to estimate the overall tumor burden at baseline to which subsequent measurements will be compared. The same method of assessment and the same technique should be used to characterize each lesion at baseline and during follow-up.~The best overall response based on RECIST is the best response recorded from registration until disease progression/recurrence, taking as reference for progressive disease the smallest measurements recorded since registration. The best response was determined based on the tumor responses in target and nontarget lesions, with or without new lesions. To be assigned a status of complete or partial response, changes in tumor measurements must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. To be assigned a status of stable disease, measurements must have met the stable disease criteria at least once after study entry at a minimum interval of 8 weeks." (NCT00077376)
Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

InterventionParticipants (Number)
Compelete ResponsePartial ResponseNo Change/ StableProgressionUnevaluable
Trastuzumab/Ixabepilone/Carboplatin42215162

[back to top]

Kaplan-Meier Estimate of Overall Survival at 3 Years for All Treated Patients

Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years. (NCT00077376)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years

InterventionPercentage of Participants (Number)
Trastuzumab/Ixabepilone/Carboplatin48

[back to top]

Time to Disease Progression for All Treated Patients

This interval will be measured from the date of entry on the study to the appearance of new metastatic lesions or objective tumor progression based on RECIST. Patients progression-free at last follow-up were censored. (NCT00077376)
Timeframe: Assessed every 3 cycles during induction therapy and every 6 cycles during maintenance therapy until disease progression or up to 5 years

InterventionMonths (Median)
Trastuzumab/Ixabepilone/Carboplatin8.2

[back to top]

Kaplan-Meier Estimate of Overall Survival at 3 Years for HER2+ Patients

Survival estimate from the Kaplan-Meier curve of the proportion of patients alive at 3 years. (NCT00077376)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years

InterventionPercentage of Participants (Number)
Trastuzumab/Ixabepilone/Carboplatin50

[back to top]

Event-free Survival Rate (EFSR) Defined as the Need for Non-protocol Chemotherapy, Enucleation, or EBRT at the Patient Level

EFSR will be estimated for patients who respond to vincristine and carboplatin after an initial 1 cycle of chemoreduction (NCT00079417)
Timeframe: 2 years after enrollment

InterventionProportion of participants (Number)
Vincristine Sulfate and Carboplatin and Surgery0.60

[back to top]

Event-free Survival

Proportion of patients with event free survival at 2 years. An event is defined as the need for non-protocol therapy, defined as additional on-protocol chemotherapy, enucleation or external beam radiation, among patients with Group B intraocular tumors with a schedule of neoadjuvant 2-agent (Vincristine/Carboplatin) chemotherapy (chemo-reduction) and standardized local ophthalmic therapy. (NCT00079417)
Timeframe: At 2 years

InterventionProportion of participants (Number)
Vincristine Sulfate and Carboplatin and Surgery0.65

[back to top]

Response Rate (RR) at Eye Levels After the First Course of Therapy

RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number eyes with Type I, II, III or IV response after first course of therapy (NCT00079417)
Timeframe: 1 month after enrollment

InterventionProportion of eyes (Number)
Vincristine Sulfate and Carboplatin and Surgery0.71

[back to top]

Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0

Participants with Grade 3 and higher reported on protocol therapy (NCT00079417)
Timeframe: 6 months after enrollment

InterventionParticipants (Number)
Incidence of Catheter Related InfectionIncidence of Upper Respiratory InfectionIncidence of DehydrationIncidence of UrticariaIncidence of Neutrophils
Vincristine Sulfate and Carboplatin and Surgery11116

[back to top]

Response Rate (RR) at Patient Level After the First Course of Therapy

RR will be estimated. The response after 1 course of chemotherapy will be used to better define response to this neoadjuvant systemic chemotherapy, prior to the use of local ophthalmic therapy. Response to subsequent courses will help define response to combined systemic chemotherapy and local ophthalmic therapy. Number of patients with Type I, II, III or IV response after first course of therapy (NCT00079417)
Timeframe: 1 month after enrollment

InterventionProportion of participants (Number)
Vincristine Sulfate and Carboplatin and Surgery0.71

[back to top]

Number of Participants With a Response to Regimen B

To assess the complete response rate to pre-radiotherapy chemotherapy (Reg B only). Response was determined after completing 2-4 cycles of chemotherapy on Reg B. Complete Response (CR) is defined as disappearance of all target lesions. (NCT00085098)
Timeframe: 5 years from beginning of treatment

InterventionParticipants (Count of Participants)
Regimen B (Chemotherapy Plus Radiotherapy)8

[back to top]

Event-free Survival

"Data will be summarized as number of patients in the following categories at the time of data cutoff for analyses of 3-year EFS: 1)Experienced a qualifying event (QE) (see below);2)Event-free through 3 years of follow-up;3)Event-free until data cutoff (if less than 3 years of follow-up);4)Withdrew from study;5)Lost to follow-up.~QEs: 1)disease progression, defined as increase >= 40% in tumor volume or >= 25% in tumor area of target lesions;2)development of new lesions;3)occurrence of a second malignant neoplasm, defined as a malignancy with different histological type from trial-qualifying diagnosis;4)death from any cause.~Stat. analyses will be based on time from enrollment to the earliest of: 1)occurrence of any of the QEs;2)withdrawal from study or lost to follow-up;3)completion of three years of follow-up event-free;4)data cutoff for completion of the statistical analyses for the protocol's primary objective.~NOTE: Reported data are through May 2009 (see Caveats section)." (NCT00085098)
Timeframe: Study enrollment until date of earliest qualifying event (QE), date last known to be QE-free if the patient is followed for less than three years and is QE-free at the time of analysis, or 3 years if the patient is QE-free at 3 years

,
Interventionparticipants (Number)
Experienced a qualifying eventEvent-free through 3 years of follow-upEvent-free at data cutoff (if < 3 years follow-up)Withdrew from study prior to 3 years of follow-upLost to follow-up prior to 3 years of follow-up
Regimen A (Radiotherapy Only)10900
Regimen B (Chemotherapy Plus Radiotherapy)101100

[back to top]

Quality of Life (QOL) and Neurocognitive Assessment (NP)

The primary endpoints for QOL and NP assessments will be the global scale value from each of these instruments at the two-year time point. Analyses of subscales (if they exist) and of assessments at other times will be of secondary interest. It is assumed that scale values are standardized to a reference normal population. The scores range from 0 to 100 with higher score reflecting better QoL or neurocognitive assessment. (NCT00085098)
Timeframe: 2 years from beginning of treatment

,
InterventionScores on a scale (Mean)
Overall IQ ScoreSelf Report Score-Internalizing ProblemsSelf Report Score-Emotional ProblemsSelf Report Score-Personal Adjustment StrengthsParent Report QoL Total ScoreSelf Report QoL Total Score
Regimen A (Radiotherapy Only)98.6041.0044.0051.5088.0495.65
Regimen B (Chemotherapy Plus Radiotherapy)92.4342.5042.0060.5079.3590.76

[back to top]

Toxicity and Safety as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

The analysis of toxicity will focus on estimating the rates of key acute and subacute toxicity occurring during the first induction chemotherapy. The list of toxicities of interest include Anemia or Febrile Neutropenia; Nausea or Vomiting; Infections and Infestations; Neutrophil or White blood count decrease; and Hypokalemia or Hyponatremia (NCT00085098)
Timeframe: From the beginning of treatment, assessed up to 5 years

InterventionParticipants (Count of Participants)
Anemia or Febrile NeutropeniaNausea or VomitingInfections and InfestationsNeutorphil or White blood count decreaseHypokalemia or Hyponatremia
Regimen B (Chemotherapy Plus Radiotherapy)22273

[back to top]

Overall Survival

Median number of months from first study treatment until time of death (NCT00085839)
Timeframe: From first study treatment until time of death (maximum 26.8 months)

Interventionmonths (Median)
Erlotinib6.57
Standard Chemotherapy9.53

[back to top]

Progression-free Survival

Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression or death in absence of progression. (NCT00085839)
Timeframe: Until time of disease progression (maximum 5 months)

Interventionmonths (Median)
Erlotinib1.91
Standard Chemotherapy3.52

[back to top]

Best Tumor Response

Change in size of tumor: Complete Response (CR) = no measurable tumor; Partial Response (PR) = 30% decrease in size of measurable tumor; Stable Disease (SD) = measurable tumor size has not changed; Progressive Disease (PD) = measurable tumor 20% larger than at baseline. (NCT00085839)
Timeframe: While receiving study treatment (maximum 60 weeks)

,
Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Unable to Determine/Not Evaluable
Erlotinib0219238
Standard Chemotherapy06231012

[back to top]

Proportion of Patients With Objective Response by RECIST

Per RECIST criteria, Complete response (CR)= disappearance of all target and nontarget lesions Partial response (PR)= >=30% decrease in the sum of the longest diameters of target lesions from baseline, and persistence of one or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits. Objective response = CR + PR. (NCT00089297)
Timeframe: Assessed at weeks 7, 14, 18, 20, and then every every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry

Interventionproportion of patients (Number)
Cetuximab/Paclitaxel/Carboplatin0.86

[back to top]

Progression-free Survival

Progression-free survival was defined as the time from registration to documented progression or death without progression. Progression is defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s) or unequivocal progression of existing nontarget lesions. (NCT00089297)
Timeframe: Assessed at weeks 7, 14, 18, 20, and then every every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry

InterventionMonths (Median)
Cetuximab/Paclitaxel/Carboplatin47.5

[back to top]

Overall Survival

Overall survival is defined as the time from registration to death of any causes. (NCT00089297)
Timeframe: Weekly during treatment, and then every every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry

InterventionMonths (Median)
Cetuximab/Paclitaxel/Carboplatin49.4

[back to top]

Event-free Survival Rate at 1 Year

Event-free survival rate at 1 year was defined as the proportion of patients who did not have disease progression, primary site surgery, or death after being followed for 1 year. (NCT00089297)
Timeframe: Assessed at 1 year.

Interventionproportion of patients (Number)
Cetuximab/Paclitaxel/Carboplatin0.79

[back to top]

Progression-free Survival (PFS)

"Progression in measurable disease is defined as any of the following: At least a 20% increase in the sum of the longest diameter target lesions; appearance of one or more new lesions; Death due to disease without prior objective documentation of progression; deterioration in health status attributable to the disease requiring a change in therapy without objective documentation of progression~Progression in non-measurable disease according to CA125 levels is defined as any of the following: CA125 that begins in normal range increases to twice the upper limit of normal; CA125 level that begins elevated increases 25% over two previous samples, a 50% increase over three previous samples, or a persistent elevation over 100 U/ml for more than 2 months without a 50% decrease." (NCT00090610)
Timeframe: Every 6 months, to 18 months

Interventionmonths (Median)
Arm 113.7
Arm 28.4

[back to top]

Objective Response Rate

"Complete response rate plus partial response rate, where: Complete response (CR) is defined as disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart and normalization of elevated CA125 in cases of ovarian cancer; Partial response (PR) for measurable disease is defined >= 30% decrease in the sum of the longest dimensions of all target measurable lesions with no unequivocal progression of non-target lesions as well as no new lesions, with documentation by two disease assessments at least four weeks apart. PR according to CA125 levels is defined as a 50% decrease in CA125 levels where two initial samples were elevated and the sample that shows the 50% is confirmed by a fourth sample 28 days after the prior sample.~OR = CR + PR" (NCT00090610)
Timeframe: Every 6 months, starting at 12 months to 24 months

Interventionpercentage of participants (Number)
Arm 155.4
Arm 243.3

[back to top]

Median Overall Survival

(NCT00090610)
Timeframe: Every 6 months starting at 12 months, to 24 months

Interventionmonths (Median)
Arm 133.2
Arm 230.1

[back to top]

Recurrence-Free Survival

Recurrence-free survival is based on measurable disease using Kaplan-Meier estimates for the intent to treat (ITT) Population who achieved a complete response. (NCT00090610)
Timeframe: Every 6 months starting at 12 months, to 24 months

Interventionmonths (Median)
Arm 120
Arm 215.8

[back to top]

Quality of Life

"Quality of Life was measured using the Trial Outcome Index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, version 4. The TOI portion of the FACT-O included questions related to Physical well-being (PWB), Social/Family well-being (FWB), and an ovarian cancer specific module (OCS). The PWB score range is from 0-28; the FWB score range is from 0-28; the OCS score range is from 0-44; this gives the TOI a score range from 0-100. (TOI = PWB + FWB + OCS)~With these instruments, a higher score indicates better health-related quality of life." (NCT00090610)
Timeframe: Baseline performed 14 days before first dose, then every other cycle and at study termination

,
Interventionunits on a scale (Mean)
BaselineCycle 1Cycle 2Cycle 3Cycle 4Cycle 5Cycle 6End of Study
Arm 176.365.172.769.470.869.374.371.4
Arm 276.673.375.375.676.074.081.278.0

[back to top]

Time to Disease Progression

Time to disease progression was measured from the date of first dose of study drug to the start of disease progression. Patients who did not have disease progression at the end of follow-up were censored at the last known time that the patient was evaluated for progression. Progression is at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. Time to disease progression was summarized using Kaplan-Meier methods. (NCT00093145)
Timeframe: Assessed every 2 cycles, up to a maximum of 39 cycles.

Interventionmonths (Median)
Albumin-bound Paclitaxel, Carboplatin + Herceptin16.6

[back to top]

Percentage of Participants With a Total Response

Total response was defined as the percentage of participants with stable disease (SD) for ≥ 16 weeks or complete or partial overall response. Stable disease was defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Progressive disease is at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. (NCT00093145)
Timeframe: Evaluated every 2 cycles, up to a maximum of 39 cycles.

Interventionpercentage of participants (Number)
Albumin-bound Paclitaxel, Carboplatin + Herceptin81.3

[back to top]

Percentage of Participants Who Achieved an Objective Confirmed Complete or Partial Overall Response

Percentage of participants who achieved an objective confirmed complete or partial overall response based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. A complete response (CR) is the disappearance of all known disease and no new sites or disease related symptoms confirmed at least 4 weeks after initial documentation. A partial response (PR) is at least a 30% decrease in the sum of the longest diameters of target lesions, taking as a reference the baseline sum of the longest diameters confirmed at least 4 weeks after initial documentation. PR is also recorded when all measurable disease has completely disappeared, but a non-measurable component (i.e., ascites) is still present but not progressing, or with the persistence of one or more non-target lesions and/or the maintenance of tumor marker level above the normal limits. (NCT00093145)
Timeframe: Objective response was evaluated every 2 cycles, up to a maximum of 39 cycles (approximately 39 months)

InterventionPercentage of participants (Number)
Albumin-bound Paclitaxel, Carboplatin + Herceptin62.5

[back to top]

Duration of Response

Duration of response was evaluated by measuring progression-free survival for participants with a complete response or partial response. Progression-free survival was defined as the time from the first dose of study drug to the start of progression or patient death (whichever occurred first). Participants who did not have progression or were still alive were censored at the last known time the patient was progression free. Patients that initiated other anticancer therapy prior to progression were censored at the time when new anticancer therapy was initiated. Progression is at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum of the longest diameters recorded since the treatment started; or the appearance of one or more new lesions; or the unequivocal progression of a non-target lesion. (NCT00093145)
Timeframe: Assessed every 2 cycles, up to a maximum of 39 cycles.

Interventionmonths (Median)
Albumin-bound Paclitaxel, Carboplatin + Herceptin17.8

[back to top]

Overall Patient Survival

Overall survival was defined as the time from the day of randomization to patient death (due to any cause), as assessed by post study follow-up on a monthly basis for 3 months and every 3 months. Participants still alive were censored at the last known time that the patient was alive. Patient survival was estimated using Kaplan-Meier methods. (NCT00093145)
Timeframe: From Day 1 until approximately 44 months.

Interventionmonths (Median)
Albumin-bound Paclitaxel, Carboplatin + HerceptinNA

[back to top]

Number of Participants With Adverse Events (AEs)

A Treatment-emergent AE was any AE that began or worsened after the start of study drug through 30 days after the last dose of study drug or end of study whichever is later. A treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE) on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence at any dose that: is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above (NCT00093145)
Timeframe: Day 1 up to 39 cycles

Interventionparticipants (Number)
Number with any treatment emergent AENumber with any treatment-related AENumber with any Grade 3/4 TEAENumber with any serious AE
Albumin-bound Paclitaxel, Carboplatin + Herceptin3231205

[back to top]

The Primary Endpoint of This Trial is the Proportion of Patients Alive at 1 Year. Phase II Patients Only.

The primary endpoint of this trial is the proportion of patients alive at 1 year (i.e., 365 days) after study registration. Proportion of successes, defined as the number of patients alive at one year divided by the total number of evaluable patients. (NCT00093756)
Timeframe: At 1 year

Interventionproportion of Participants (Number)
PhaseII0.73

[back to top]

Confirmed Tumor Response

Response was assessed using the RECIST v1.1 criteria. Patients were evaluated at 4 weeks post-RT, 3 months post-RT, every 3 months for 1 year post-RT, and every 6 months thereafter for a maximum of 5 years from time of registration. A Complete Response (CR) is defined as the disappearance of all target lesions. A Partial Response (PR) is defined as at least a 20% decrease in the sum of the longest diameter of target lesions from baseline. A confirmed response is defined as a CR or PR as the objective status on 2 consecutive evaluations at least 4 weeks apart. (NCT00093756)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Complete Response (CR)Partial Response (PR)
PhaseII34

[back to top]

Frequency and Severity of Observed Toxicity, Graded by Common Terminology Criteria for Adverse Events (CTCAE)

Toxicity was reported after the first 21 days of treatment and after each 28 day cycle thereafter. Events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. The number of patients reporting grade 3 and higher are tabulated. (NCT00093756)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Grade 3 Adverse EventGrade 4 Adverse Event
Phase II2215

[back to top]

Overall Survival

Overall Survival is defined as the time from registration to the time to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT00093756)
Timeframe: From registration to death due to any cause, up to 5 years

Interventionmonths (Median)
Phase II25

[back to top]

Progression-free Survival

The distribution of progression-free survival (PFS) is defined as the time from registration to the time of progression or death, whichever comes first. The PFS will be estimated using the method of Kaplan-Meier. (NCT00093756)
Timeframe: From study registration to the first of either death due to any cause or progression, up to 5 years

Interventionmonths (Median)
Phase II8.4

[back to top]

Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 2

The maximal observed plasma concentration of motesanib in Cycle 2, after multiple doses. For the 75 mg BID cohorts, Cmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD148
Paclitaxel/Carboplatin + Motesanib 125 mg QD748
Paclitaxel/Carboplatin + Motesanib 75 mg BID390
Panitumumab + Motesanib 50 mg QD265
Panitumumab + Motesanib 125 mg QD672
Panitumumab + Motesanib 75 mg BID242
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD651

[back to top]

Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 2

The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionhours (Mean)
Paclitaxel/Carboplatin + Motesanib 125 mg QD6.41
Paclitaxel/Carboplatin + Motesanib 75 mg BID6.36
Panitumumab + Motesanib 50 mg QD7.08
Panitumumab + Motesanib 125 mg QD4.90

[back to top]

Estimated Terminal-phase Half-life (t1/2,z) of Motesanib in Cycle 1

The terminal-phase elimination half-life (t1/2,z) of motesanib was calculated as ln(2)/λz. The terminal elimination rate constant (λz) was determined by linear regression of the natural logarithms of at least the last 3 measurable concentrations during the terminal phase. For the 75 mg BID cohorts, t1/2,z is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours postdose.

Interventionhours (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD7.34
Paclitaxel/Carboplatin + Motesanib 125 mg QD5.33
Paclitaxel/Carboplatin + Motesanib 75 mg BID5.77
Panitumumab + Motesanib 50 mg QD6.47
Panitumumab + Motesanib 125 mg QD7.57
Panitumumab + Motesanib 75 mg BID8.28

[back to top]

Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Post-dose for Motesanib in Cycle 2

Area under the plasma concentration-time curve from time 0 to 24 hours post-dose (AUC0-24) for motesanib in Cycle 2 calculated using the using the linear/log trapezoidal method. For the 75 mg BID cohort AUC0-24 is the sum of AUC0-12 for the first and second daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionμg*hr/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 125 mg QD4.50
Paclitaxel/Carboplatin + Motesanib 75 mg BID3.11
Panitumumab + Motesanib 50 mg QD1.26
Panitumumab + Motesanib 125 mg QD3.92
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD3.16

[back to top]

Area Under the Plasma Concentration-time Curve for Motesanib in Cycle 1

Area under the plasma concentration-time curve for motesanib in Cycle 1 calculated using the using the linear/log trapezoidal method. AUC from time zero to infinity (AUC0-inf) is reported for the 50 and 125 mg QD cohorts and AUC from time 0 to 24 hours post-dose (AUC0-24) is reported for the 75 mg BID cohort, where AUC0-24 is the sum of AUC0-12 for the first and second daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionμg*hr/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD0.971
Paclitaxel/Carboplatin + Motesanib 125 mg QD3.21
Paclitaxel/Carboplatin + Motesanib 75 mg BID2.91
Panitumumab + Motesanib 50 mg QD1.74
Panitumumab + Motesanib 125 mg QD3.23
Panitumumab + Motesanib 75 mg BID2.04

[back to top]

Maximum Observed Plasma Concentration of Motesanib (Cmax) in Cycle 1

The maximal observed plasma concentration of motesanib after a single dose dose in Cycle 1. For the 75 mg BID cohorts, Cmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD158
Paclitaxel/Carboplatin + Motesanib 125 mg QD525
Paclitaxel/Carboplatin + Motesanib 75 mg BID448
Panitumumab + Motesanib 50 mg QD328
Panitumumab + Motesanib 125 mg QD444
Panitumumab + Motesanib 75 mg BID198
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD360

[back to top]

Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 2

The trough plasma concentration for motesanib at 24 hours postdose in Cycle 2. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose). (NCT00094835)
Timeframe: Cycle 2, Day 1, 24 hours post-dose

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 125 mg QD43.4
Paclitaxel/Carboplatin + Motesanib 75 mg BID45.4
Panitumumab + Motesanib 50 mg QD10.4
Panitumumab + Motesanib 125 mg QD61.1
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD45.1

[back to top]

Trough Plasma Concentration at 24 Hours Post-dose (C24) for Motesanib in Cycle 1

The trough plasma concentration for motesanib at 24 hours postdose in Cycle 1. For the 75 BID cohort, C24 is the observed concentration at 24 hours (ie, after the second daily dose). (NCT00094835)
Timeframe: Cycle 1, Day 3, 24 hours post-dose

Interventionng/mL (Mean)
Paclitaxel/Carboplatin + Motesanib 50 mg QD9.12
Paclitaxel/Carboplatin + Motesanib 125 mg QD26.5
Paclitaxel/Carboplatin + Motesanib 75 mg BID56.7
Panitumumab + Motesanib 50 mg QD14.0
Panitumumab + Motesanib 125 mg QD32.5
Panitumumab + Motesanib 75 mg BID56.8

[back to top]

Time to Maximum Plasma Concentration of Motesanib (Tmax) in Cycle 2

The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 2. For the 75 mg BID cohorts, Tmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 2, Day 1 at predose, 15 and 30 min, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionhours (Median)
Paclitaxel/Carboplatin + Motesanib 50 mg QD1.5
Paclitaxel/Carboplatin + Motesanib 125 mg QD1.0
Paclitaxel/Carboplatin + Motesanib 75 mg BID0.63
Panitumumab + Motesanib 50 mg QD1.0
Panitumumab + Motesanib 125 mg QD0.75
Panitumumab + Motesanib 75 mg BID1.0
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD2.0

[back to top]

Time to Maximum Plasma Concentration of Motesanib (Tmax) for Cycle 1

The time after dosing that the maximal plasma concentration of motesanib was observed in Cycle 1. For the 75 mg BID cohorts, Tmax is reported for the first daily dose. (NCT00094835)
Timeframe: Cycle 1, Day 3 at predose, 15 and 30 minutes, and at 1, 2, 4, 6, 10 (QD cohorts only), and 24 hours post-dose.

Interventionhours (Median)
Paclitaxel/Carboplatin + Motesanib 50 mg QD0.75
Paclitaxel/Carboplatin + Motesanib 125 mg QD1.0
Paclitaxel/Carboplatin + Motesanib 75 mg BID0.75
Panitumumab + Motesanib 50 mg QD1.5
Panitumumab + Motesanib 125 mg QD1.0
Panitumumab + Motesanib 75 mg BID0.58
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD1.0

[back to top]

Percentage of Participants With an Overall Objective Response

Confirmed objective tumor response defined as a complete response (CR) or partial response (PR) using modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Tumor response was evaluated by computed tomography (CT) scan or magnetic resonance imaging (MRI). Responding disease (CR or PR) was confirmed no less than 4 weeks after the criteria for response were first met. A complete response defined as the disappearance of all target lesions and all non-target lesions, no new lesions and normalization of tumor marker level. Partial response defined as either the disappearance of all target lesions and the persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diamer (LD) of target lesions, taking as reference the baseline sum LD and no new lesions and/or unequivocal progression of existing non-target lesions. (NCT00094835)
Timeframe: After 9 weeks of treatment (at the end of Cycle 3)

InterventionPercentage of participants (Number)
Paclitaxel/Carboplatin + Motesanib 50 mg QD33
Paclitaxel/Carboplatin + Motesanib 125 mg QD18
Paclitaxel/Carboplatin + Motesanib 75 mg BID0
Panitumumab + Motesanib 50 mg QD0
Panitumumab + Motesanib 125 mg QD0
Panitumumab + Motesanib 75 mg BID0
Panitumumab + Paclitaxel/Carboplatin + Motesanib 125 mg QD17

[back to top]

Duration of Grade 2 or Higher Dysphagia

"Duration of grade 2 or higher dysphagia was calculated in days from the onset (first occurrence of grade ≥ 2) to the resolution (grade ≤ 1 after the last grade ≥ 2) of dysphagia.~Participants with no assessments were assumed as having grade ≥ 2 dysphagia and with a duration of the mean duration of all participants." (NCT00094861)
Timeframe: Start of treatment through Week 16

Interventiondays (Mean)
Placebo32.4
Palifermin25.3

[back to top]

Number of Participants With Unplanned Breaks in Radiotherapy

The number of participants with unplanned breaks in radiotherapy of ≥ 5 days or who discontinued radiotherapy during Week 1 to Week 6. (NCT00094861)
Timeframe: Week 1 to Week 6

,
Interventionparticipants (Number)
YesNoDid not receive radiotherapy
Palifermin9382
Placebo15292

[back to top]

Number of Participants With Severe (Grade 3 or Higher) Dysphagia

"Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade ≤ 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following:~Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation)." (NCT00094861)
Timeframe: Start of treatment through Week 16

,
Interventionparticipants (Number)
YesNoNo assessment
Palifermin11371
Placebo13321

[back to top]

Number of Participants With Grade 2 or Higher Dysphagia

"Participants underwent acute dysphagia assessments twice weekly during Weeks 1 through 7, and twice weekly thereafter (Weeks 8 through 12) and once weekly after Week 12 until dysphagia resolved to grade ≤ 1 but not beyond Week 16. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following:~Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation)." (NCT00094861)
Timeframe: Start of treatment through Week 16

,
Interventionparticipants (Number)
YesNoNo assessment
Palifermin30181
Placebo32131

[back to top]

Number of Participants Hospitalized

(NCT00094861)
Timeframe: Baseline to Week 16

,
Interventionparticipants (Number)
HospitalizedNot hospitalized
Palifermin3415
Placebo3115

[back to top]

Maximal Eastern Cooperative Oncology Group (ECOG) Performance Status Increase

"Maximal increase from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a scale to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient, and determine appropriate treatment and prognosis.~Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; Grade 2: Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair; Grade 5: Dead." (NCT00094861)
Timeframe: Baseline through Week 12

Interventionunits on a scale (Mean)
Placebo1.5
Palifermin0.9

[back to top]

Maximal Dysphagia Grade

"The mean maximal grade of dysphagia for each participant during the study. Dysphagia (difficulty swallowing) was graded using the Common Terminology Criteria for Adverse Events, Version 3.0 (CTCAE v3.0) dysphagia scale according to the following:~Grade 1: Symptomatic, able to eat regular diet; Grade 2: Symptomatic and altered eating/swallowing (e.g., altered dietary habits, oral supplements), IV fluids indicated <24 hours; Grade 3: Symptomatic and severely altered eating/swallowing (e.g., inadequate oral caloric or fluid intake), IV fluids, tube feedings, or total parenteral nutrition (TPN) indicated ≥24 hours; Grade 4: Life-threatening consequences (e.g., obstruction, perforation)." (NCT00094861)
Timeframe: Start of treatment through Week 16

Interventiongrade (Mean)
Placebo1.9
Palifermin1.8

[back to top]

Maximal Body Weight Loss

Maximal weight loss observed from Baseline through to Week 12. (NCT00094861)
Timeframe: Baseline through Week 12

Interventionkilograms (Mean)
Placebo4.63
Palifermin5.44

[back to top]

Progression-free Survival and Disease-specific Survival as Assessed by Disease Progression or Death and Log Rank Tests at the Median, and 2, 3, and 5 Years

Progression free survival was defined as the time from date of randomisation to disease progression or death from any cause without progression whichever occurred first; otherwise, patients were censored at the date last known to be free of progression. (NCT00095875)
Timeframe: 5 years

Interventionpercent of patients (Number)
Arm I67
Arm II69

[back to top]

Overall Survival

To compare the 3-year survival achieved by docetaxel/cisplatin/5-FU based sequential therapy with platinum based chemo radiotherapy in patients with locally advanced SCCHN. Overall survival is defined as the time from date of randomisation to death from any cause. Patients alive at the time of current analysis were censored at the date last known to be alive.Kaplan-Meier method was used to estimate overall survival (NCT00095875)
Timeframe: 3-years

Interventionpercent of patients (Number)
Arm I73
Arm II78

[back to top]

Complete and Partial Response Rate Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

Patients should be reevaluated for response every 2 cycles (6 weeks). Patients who continue on Arm A of treatment for more than 12 months should be reevaluated for response every 3 cycles (9 weeks). In addition to a baseline scan, confirmatory scans should also be obtained 4 weeks following initial documentation of objective response. (NCT00096200)
Timeframe: after 6 weeks (2 cycles)

,,
Interventionparticipants (Number)
Partial ResponseProgressive DiseaseStable DiseaseComplete Response
Arm A2830
Arm B11174
Arm C: Crossover From Arm A to B1040

[back to top]

Evaluate the Progression-free Survival Rate

Progression free survival (PFS) was measured by months from the date of treatment to the date of death or the date of progression, and censored at the date of last follow-up for those alive without progression. (NCT00096200)
Timeframe: up to 85 months of follow-up

Interventionmonths (Median)
Arm A5.6
Arm B16.8
Arm C: Crossover From Arm A to B16.8

[back to top]

Overall Survival

Overall survival time, in months, is calculated from the date of treatment to date of death, and to date of last follow-up for those still alive. (NCT00096200)
Timeframe: up to 85 months of follow-up

Interventionmonths (Median)
Arm A25.6
Arm B25.9
Arm C: Crossover From Arm A to B25.9

[back to top]

Distribution of R0, R1, and R2 Resections After Chemotherapy

An R0 resection is defined as a complete resection of all disease with negative margins and the highest lymph node resected negative for residual tumor. An R1 resection is defined as a complete resection of all disease with pathology of positive margins, pathologic evidence of tumor cells in the highest lymph node resected in the mediastinum, or extracapsular nodal spread. An R2 resection is defined as gross residual disease left behind after surgical resection. (NCT00096226)
Timeframe: At time of surgery (16-18 weeks)

Interventionpercentage of participants (Number)
R0R1R2
Chemoradiation, Surgery, Chemotherapy75.724.30

[back to top]

Distribution of Highest Grade Adverse Event

The number of patients whose highest grade adverse event (AE) reported was 3, 4, or 5 was calculated. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Number of patients with highest grade of 3, 4, and 5 are presented. (NCT00096226)
Timeframe: From start of treatment to end of follow-up, a maximum of 64.3 months

Interventionpercentage of participants (Number)
Grade 3Grade 4Grade 5
Chemoradiation, Surgery, Chemotherapy49.119.31.8

[back to top]

Progression-free Survival at Two Years

Progression is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. An event for progression-free survival is the first occurrence of progression or death due to any cause. Progression-free survival time is defined as the time from study entry to the the date progression or death, or last known follow-up (censored) if neither progression nor death occurred. Progression-free survival rate is estimated using the Kaplan-Meier method. (NCT00096226)
Timeframe: From registration to two years

Interventionpercentage of participants (Number)
Chemoradiation, Surgery, Chemotherapy32.7

[back to top]

Percentage of Patients With Complete Pathological Response After Concurrent Chemotherapy and Radiation Therapy

Complete pathologic response is defined as complete resection achieved and no evidence of viable tumor in the entire resection specimen. (NCT00096226)
Timeframe: At time of surgery (16-18 weeks)

Interventionpercentage of participants (Number)
Chemoradiation, Surgery, Chemotherapy8.1

[back to top]

Percentage of Patients Able to Undergo Surgical Resection

(NCT00096226)
Timeframe: At time of surgery (16-18 weeks)

Interventionpercentage of participants (Number)
Chemoradiation, Surgery, Chemotherapy64.9

[back to top]

Overall Survival at Two Years

Overall survival time is defined as time from registration to the date of death from any cause. Overall survival rate is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (NCT00096226)
Timeframe: From registration to two years

Interventionpercentage of participants (Number)
Chemoradiation, Surgery, Chemotherapy53.8

[back to top]

Mediastinal Nodal Clearance Rate

If at least 12 of the first 21 evaluable patients and at least 27 of the the first 45 evaluable patients have mediastinal nodal clearance (MNC), then a conclusion of a 70% MNC rate (compared to 50%) is made using Simon's two-stage design with 90% power and 10% type I error. (NCT00096226)
Timeframe: At completion of concurrent chemotherapy and radiation therapy, up to 14 weeks.

Interventionparticipants (Number)
Chemoradiation, Surgery, Chemotherapy27

[back to top]

Percentage of Patients With Major Surgical Morbidities Within 30 Days of Surgery

The surgical morbidities occurring within 30 days following resection were assessed and graded using the NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0. A major morbidity is considered a grade 3 or higher of any of the following: pneumonitis, infection, atelectasis, chest tube drainage/bronchial stump leak, pneumothorax, chylothorax, cardiac ischemia/infarction, pulmonary thrombosis/embolism, supraventricular atrial arrhythmia, ventricular arrhythmia, post-operative hemorrhage, pulmonary/upper respiratory fistula, pleural effusion, or death. (NCT00096226)
Timeframe: From 0 to 30 days following surgery (surgery occurs within 16-18 weeks after registration)

Interventionpercentage of participants (Number)
Chemoradiation, Surgery, Chemotherapy21.6

[back to top]

Best Overall Response by RECIST Criteria (Version 1.0)

Number of eligible, treated participants in each response category by RECIST criteria. Response categories represent best response for each patient prior to progression. (NCT00101283)
Timeframe: Assessed every 2 cycles (6 weeks) while on treatment, then every 3 months for 2 years, then every 6 months for 1 year until disease progression

,
Interventioneligible, treated participants (Number)
Partial ResponseStable DiseaseProgressionUnevaluable
Pemetrexed/Carboplatin3751
Pemetrexed/Gemcitabine0652

[back to top]

Progression-Free Survival

Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored. (NCT00101283)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 1 year

InterventionMonths (Median)
Pemetrexed/Carboplatin4.1
Pemetrexed/Gemcitabine3.3

[back to top]

Overall Survival

Time from randomization to death. Patients alive at last follow-up were censored. (NCT00101283)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 1 year

InterventionMonths (Median)
Pemetrexed/Carboplatin13.0
Pemetrexed/Gemcitabine6.0

[back to top]

Overall Survival

Overall survival is defined as time from study entry to death from any cause. The comparison of overall survival was conducted in intention-to-treat population. (NCT00110019)
Timeframe: Survival was assessed every 3 months if patient is < 2 years from study entry. Every 6 months is patient is 2-5 years from study entry.

Interventionmonths (Median)
Arm I (Carboplatin + Paclitaxel + Sorafenib)11.1
Arm II (Carboplatin + Paclitaxel+Placebo)11.3

[back to top]

Progression-free Survival

Progression-free survival was defined as time from study entry to disease progression or death from any cause, whichever occurred first. Patients without disease progression were censored at last date of assessment. Disease progression was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. (NCT00110019)
Timeframe: Tumor response was assessed after every 2 cycles during cycle 1 through 10, and every 3 cycles after cycle 10. Survival was assessed every 3 months if patient is < 2 years from study entry, and every 6 months if 2-5 years from study entry.

Interventionmonths (Median)
Arm I (Carboplatin + Paclitaxel + Sorafenib)4.9
Arm II (Carboplatin + Paclitaxel+Placebo)4.2

[back to top]

Objective Response (Complete and Partial Response) Rate

Tumor response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0. Objective response =complete response (CR) + partial response (PR). Complete response is defined as disappearance of all target lesions. Partial response is defined as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum of longest diameters. (NCT00110019)
Timeframe: Tumor response was assessed after every 2 cycles during cycle 1 through 10. After cycle 10, tumor response was assessed after every 3 cycles.

Interventionproportion (Number)
Arm I (Carboplatin + Paclitaxel + Sorafenib)0.205
Arm II (Carboplatin + Paclitaxel+Placebo)0.182

[back to top]

Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status to the Visit When the Best Tumor Response Was Noted

Change in ECOG PS is defined as an improvement (increase) or worsening (decrease) of at least one grade from the baseline ECOG score (from 0 [fully active] to 5 [dead]). Change in ECOG PS was recorded at the visit at which best confirmed response (BCR) using the modified RECIST (PR, CR, stable disease or Progressive Disease (PD)) was first noted (the change was 7% for both Sorafenib and Placebo). The BCR is the BCR recorded from the start of the treatment until DP/recurrence (taking as reference for DP, the smallest measurements recorded since treatment started). (NCT00111007)
Timeframe: baseline and at visit when best response was noted (maximum treatment duration of 68.3 weeks)

,
Interventionparticipants (Number)
missingbetterno changeworse
Carboplatin/Paclitaxel (C/P)4108239
Sorafenib (Nexavar, BAY43-9006)1097046

[back to top]

Overall Survival (OS)

Overall survival (OS) was calculated as the number of days from date of randomization to death date. Subjects who had not died at the time of analysis were censored at their last contact date. (NCT00111007)
Timeframe: Time from randomization to death (median time of 294 days)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006)294
Carboplatin/Paclitaxel (C/P)294

[back to top]

Progression Free Survival (PFS)

PFS was calculated as the time (days) from date of randomization to date of first observed DP (per modified Response Evaluation Criteria In Solid Tumors [RECIST] or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease) or death due to any cause, if death occurred before progression was documented. The actual date of tumor assessments was used for this calculation. PFS for subjects without progression or death was censored at the last date of tumor evaluation. PFS for subjects who had no tumor assessments after baseline and did not die was censored at 1 day. (NCT00111007)
Timeframe: Time from randomization to documented tumor progression or death (median time of 124 days)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006)122
Carboplatin/Paclitaxel (C/P)125

[back to top]

Duration of Response (DOR)

Duration of response was defined as the time from the first documented objective response of Partial Response (PR: At least a 30% decrease in the sum of the longest diameter [SLD] of target lesions, taking as reference the baseline SLD or better) or Complete Response (CR: Disappearance of all target lesions), whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Duration of response for subjects who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. (NCT00111007)
Timeframe: Time from initial response to documented tumor progression or death (median time of 197 days)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006)228
Carboplatin/Paclitaxel (C/P)166

[back to top]

Time to Progression (TTP)

TTP was calculated as the time (days) from date of randomization to date of first observed disease progression (DP) (per modified RECIST or clinical judgment, whichever was earlier: CR, PR, stable disease, progressive disease). The actual dates of tumor assessments were used for this calculation. TTP for subjects without disease progression at the time of analysis, including subjects with death prior to progression, was censored at the last date of tumor evaluation. TTP for subjects who had no tumor assessments after baseline was censored at 1 day. (NCT00111007)
Timeframe: Time from randomization to documented tumor progression (median time of 126 days)

Interventiondays (Median)
Sorafenib (Nexavar, BAY43-9006)126
Carboplatin/Paclitaxel (C/P)126

[back to top]

Median Number of Months of Response

Median number of months of response (time from first occurrence of CR/PR to date of PD/death, [per IRRC assessment,using modified WHO criteria]) calculated for participants whose best response=CR/PR.For participants who did not progress/die, date of last tumor assessment used.CR:disappearance of all index/non-index lesions;PR:>= 50% reduction in SOPD of index lesions compared with baseline, no evidence of progression.No new lesions present.PD:>=25% increase in SOPD of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. (NCT00112294)
Timeframe: Time from first occurrence of CR or PR (whichever was recorded first) to the date of PD, death or date of last tumor assessment (up to 19 months).

InterventionMonths (Median)
Cetuximab+Taxane+Carboplatin (C/T/C)5.55
Taxane+Carboplatin (T/C)4.90

[back to top]

Median Number of Months of Survival

The median number of months of survival was defined as the time from randomization to the date of death. For participants who did not die, the date of last contact was used. (NCT00112294)
Timeframe: From randomization to death or date of last contact (up to 41 months).

InterventionMonths (Median)
Cetuximab+Taxane+Carboplatin (C/T/C)9.69
Taxane+Carboplatin (T/C)8.38

[back to top]

Number of Participants Experiencing Other Significant AEs: Acneform Rash

"An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term acneform rash were of particular importance. These AEs were: rash, rash pustular, rash erythematous, dermatitis acneiform, dermatitis exfoliative, rash papular, rash pruritic, rash generalised, rash macular, rash maculo-papular, acne, acne pustular, skin desquamation and dry skin." (NCT00112294)
Timeframe: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

InterventionParticipants (Number)
Cetuximab+Taxane+Carboplatin (C/T/C)246
Taxane+Carboplatin (T/C)56

[back to top]

Number of Participants Experiencing Other Significant AEs: Cardiac AEs

"An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term cardiac AE were of particular importance. These AEs, coded as preferred or other level Medical Dictionary for Regulatory Activities [MedDRA] terms were: coronary artery disorders, cardiac arrhythmias, heart failures not elsewhere classified, left ventricular failures, sudden cardiac death, cardiac death and sudden death." (NCT00112294)
Timeframe: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

InterventionParticipants (Number)
Cetuximab+Taxane+Carboplatin (C/T/C)58
Taxane+Carboplatin (T/C)25

[back to top]

Number of Participants With Improvement of Symptoms

Symptoms were assessed using the Functional Assessment of Cancer Therapy - Lung Cancer Subscale (FACT-LCS) questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic in all symptoms assessed) to 28 (symptom-free on all symptoms assessed). Symptom response (improvement) was defined as >= 2-point increase from baseline in score (maintained for 2 consecutive assessments, at least 3 weeks apart). Participants with a baseline score of >= 27 were not evaluable, as it would not have been possible to show an improvement. Participants with no baseline data were also not evaluable. (NCT00112294)
Timeframe: From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).

InterventionParticipants (Number)
Cetuximab+Taxane+Carboplatin (C/T/C)107
Taxane+Carboplatin (T/C)92

[back to top]

Number of Participants Who Exprienced the Most Frequent Grade 3-4 Hematology Abnormalities Occurring in >=5% Participants

Abnormalities were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTC), version 3.0. The scale is graded from 1 (least severe) to 4 (life threatening). Grade 3 and 4 criteria are defined as follows: Neutropenia: Grade 3, neutrophils <1.0 - 0.5 x 10^9/L; Grade 4, <0.5 x 10^9/L. Leukopenia: Grade 3, leukocytes <2.0 - 1.0 x 10^9/L; Grade 4, <1.0 x 10^9/L. Thrombocytopenia: Grade 3, platelets <50.0 - 25.0 x 10^9/L; Grade 4, <25.0 x 10^9/L. Anemia: Grade 3, hemoglobin <4.9 - 4.0 millimoles (mmol)/L, Grade 4, <4.0 mmol/L. (NCT00112294)
Timeframe: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

,
InterventionParticipants (Number)
NeutropeniaLeukopeniaThrombocytopeniaAnemia
Cetuximab+Taxane+Carboplatin (C/T/C)1981393317
Taxane+Carboplatin (T/C)177972915

[back to top]

Number of Participants Who Experienced the Most Frequent Grade 3-4 Serum Chemistry Abnormalities Occurring in >=5% Participants

Abnormalities were graded according to the NCI CTC, version 3.0. The scale is graded from 1 (least severe) to 4 (life threatening). Grade 3 and 4 criteria are defined as follows: Hyperglycemia (non-fasting): Grade 3, serum glucose >13.9 - 27.8 mmol/L; Grade 4 >27.8 mmol/L or acidosis. Hypomagnesemia: Grade 3, serum magnesium >1.23 - 3.30 mmol/L; Grade 4 >3.30 mmol/L. Hyponatremia: Grade 3, serum sodium <130 - 120 mmol/L; Grade 4 <120 mmol/L. Low albumin: Grade 3, serum albumin <20 g/L; Grade 4 not applicable. (NCT00112294)
Timeframe: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

,
InterventionParticipants (Number)
Hyperglycemia (non-fasting)HypomagnesemiaHyponatremiaLow albumin
Cetuximab+Taxane+Carboplatin (C/T/C)33262517
Taxane+Carboplatin (T/C)362219

[back to top]

Number of Participants With Complete Response (CR), Partial Response (PR) or Stable Disease (SD)

Disease control was defined as the number of participants whose best response was CR, PR, or SD, per the IRRC assessment, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR:>= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression (to qualify as CR or PR, no new lesions could be present); SD: participants who did not meet the criteria for CR, PR, or PD (PD:>=25% increase in SOPD of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion). (NCT00112294)
Timeframe: From randomization to end of study drug therapy (up to 174 weeks).

InterventionParticipants (Number)
Cetuximab+Taxane+Carboplatin (C/T/C)230
Taxane+Carboplatin (T/C)212

[back to top]

Number of Participants Who Died, or Experienced Other Serious Adverse Events (SAEs) and Adverse Events (AEs)

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). An SAE was defined as an AE that resulted in death, was life-threatening, required hospitalization (or prolongation of existing hospitalization), or was an important medical event. (NCT00112294)
Timeframe: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

,
InterventionParticipants (Number)
DeathSerious adverse eventsAdverse events
Cetuximab+Taxane+Carboplatin (C/T/C)38183324
Taxane+Carboplatin (T/C)27121320

[back to top]

Number of Participants Experiencing AEs Leading to Study Drug Discontinuation

An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). The results presented are stratified according to which drug was discontinued. (NCT00112294)
Timeframe: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

,
Interventionparticipants (Number)
CetuximabTaxaneCarboplatin
Cetuximab+Taxane+Carboplatin (C/T/C)1008078
Taxane+Carboplatin (T/C)05452

[back to top]

Median Change From Baseline in Symptoms, by Time Point

Symptoms were assessed using the FACT-LCS questionnaire. This 7-item scale has scores ranging from 0 (severely symptomatic) to 28 (symptom-free). The median change from baseline score was calculated at 3-weekly intervals. See also Outcome Measure 8. (NCT00112294)
Timeframe: From randomization to evidence of disease progression/death or date of last symptom assessment (up to 33 weeks).

,
InterventionUnits on a scale (Median)
3 weeks (n = 286, 257)6 weeks (n = 254, 221)9 weeks (n = 203, 175)12 weeks (n = 178, 161)15 weeks (n = 155, 121)18 weeks (n = 126, 91)21 weeks (n = 96, 43)24 weeks (n = 90, 41)27 weeks (n = 60, 22)30 weeks (n = 56, 15)33 weeks (n = 43, 7)
Cetuximab+Taxane+Carboplatin (C/T/C)1.01.01.01.01.01.02.02.03.01.52.1
Taxane+Carboplatin (T/C)0.81.01.00.01.02.03.01.03.53.03.0

[back to top]

Median Number of Months to Response

The median number of months to response was calculated for participants whose best response was CR or PR. It was defined as the time from the first dose of study therapy to the first date that criteria for PR or CR (whichever occurred first)were met. Response was assessed by the IRRC, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR: >= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression. To qualify as CR or PR, no new lesions could be present. (NCT00112294)
Timeframe: Time from first dose of study therapy to the date of PR or CR, whichever occurred first (up to 13 months).

InterventionMonths (Median)
Cetuximab+Taxane+Carboplatin (C/T/C)1.38
Taxane+Carboplatin (T/C)1.35

[back to top]

Number of Participants With Complete Response (CR) or Partial Response (PR)

Tumor response was defined as the number of participants whose best response was CR or PR, per the IRRC assessment, using the modified WHO criteria: CR: disappearance of all index/non-index lesions; PR: >= 50% reduction in the SOPD of index lesions compared with the baseline SOPD, with no evidence of progression. To qualify as CR or PR, no new lesions could be present. (NCT00112294)
Timeframe: From randomization to end of study drug therapy (up to 174 weeks).

InterventionParticipants (Number)
Cetuximab+Taxane+Carboplatin (C/T/C)87
Taxane+Carboplatin (T/C)58

[back to top]

Median Number of Months of Progression-free Survival (PFS)

Interval between randomization date & earliest date of disease progression/death due to any cause, assessed by the Independent Radiology Review Committee (IRRC) using modified World Health Organization (WHO) criteria to define progressive disease (PD): >=25% increase in sum of products of diameters (SOPD) of lesions compared with smallest SOPD recorded for study period or progression of any non-index lesion/appearance of new lesion. If no progression/death, date of last tumor assessment used. For participants who had no on-study tumor assessments & were still alive, date of randomization used. (NCT00112294)
Timeframe: From randomization to evidence of disease progression/death or date of last tumor assessment (up to 26 months).

InterventionMonths (Median)
Cetuximab+Taxane+Carboplatin (C/T/C)4.40
Taxane+Carboplatin (T/C)4.24

[back to top]

Number of Participants Experiencing Other Significant AEs: Infusion Reaction

"AE=any new untoward medical occurrence or worsening of pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs that were categorized under the composite term infusion reaction were of particular importance. These AEs were: infusion-related reaction, hypersensitivity, anaphylactic reaction, anaphylactic shock, and anaphylactoid reaction regardless of when they occurred. The terms dyspnea, pyrexia and chills were also grouped under infusion reaction, provided the onset date of these toxicities occurred on the first day of study treatment." (NCT00112294)
Timeframe: From start of study drug therapy up to 30 days after the last dose (up to 178 weeks).

InterventionParticipants (Number)
Cetuximab+Taxane+Carboplatin (C/T/C)45
Taxane+Carboplatin (T/C)18

[back to top]

Response Evaluation Criteria in Solid Tumors Criteria (RECIST) 1.0 Best Response

"Primary outcome measured according to RECIST v1.0 Best Response:~Complete Response (CR) is disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart Disease Progression is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry.~Partial Response (PR) is at least a 30% decrease in the sum of longest dimensions (LD) of all target measurable lesions taking as reference the baseline sum of LD. There can be no unequivocal progression of nontarget lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required Stable Disease is any condition not meeting the above criteria. Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy for reasons unrelated to symptoms or signs of disease." (NCT00112489)
Timeframe: Response was measured every other cycle (q 6 weeks) until disease progression is documented.

Interventionparticipants (Number)
Complete ResponsePartial ResponseStable DiseaseDisease ProgressionIndeterminate
Paclitaxel Followed by Carboplatin6191164

[back to top]

Nature and Degree of Toxicity

Number of patients who experienced grade 1 or higher serious adverse event (term or group) regardless of attribution using CTCAE v3.0 (NCT00112489)
Timeframe: During study treatment and up to 30 days after stopping study treatment

,,,,,
InterventionParticipants (Count of Participants)
LeukopeniaNeutropeniaThrombocytopeniaAnemiaOther hematologicAllergyAuditoryCardiovascularCoagulationConstitutionalFatigueAlopeciaDermatologicEndocrineGastrointestinalNauseaVomitingDiarrheaStomatitisGenitourinary/renalHemorrhageHepaticFebrile neutropeniaMetabolicCreatinineMusculoskeletalNeurologicNeuromotorSensory neuropathyOcular/visualPainMyalgiaArthralgiaPulmonary
Grade 0211744340433945339836441817353535454345452344414044144335353637
Grade 1 (CTCAE v 3.0)43191003030814782122078111001822001523345
Grade 2 (CTCAE v 3.0)2035271022141931201483200200402421216762
Grade 3 (CTCAE v 3.0)191933231101400021110001110120500102
Grade 4 (CTCAE v 3.0)12022000100000000000000000000002000
Grade 5 (CTCAE v.3.0)0000000000000000000000000000000000

[back to top]

Dose-Corrected Ctrough of SU-012662 (Sunitinib's Metabolite)

Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included. (NCT00113516)
Timeframe: predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Interventionng/mL (Mean)
Cycle 1, Day 28 (n=39)Cycle 2, Day 28 (n=28)Cycle 3, Day 28 (n=13)Cycle 5, Day 28 (n=5)
Sunitinib27.9027.3720.6422.29

[back to top]

Ctrough of Total Drug (Sunitinib + SU-012662)

Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval. (NCT00113516)
Timeframe: predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Interventionng/mL (Mean)
Cycle 1, Day 28 (n=51)Cycle 2, Day 28 (n=36)Cycle 3, Day 28 (n=16)Cycle 5, Day 28 (n=6)
Sunitinib85.2374.3559.9254.24

[back to top]

Ctrough of SU-012662 (Sunitinib's Metabolite)

Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval. (NCT00113516)
Timeframe: predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Interventionng/mL (Mean)
Cycle 1, Day 28 (n=51)Cycle 2, Day 28 (n=36)Cycle 3, Day 28 (n=16)Cycle 5, Day 28 (n=6)
Sunitinib27.5423.4718.3715.67

[back to top]

Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline

TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after stratification by < or > = median changes from baseline in VEGFR3 at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionweeks (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=30)Cycle 1, Day 1 (> = Median Cutpoint, n=30)Cycle 1, Day 28 (< Median Cutpoint, n=23)Cycle 1, Day 28 (> = Median Cutpoint, n=23)Cycle 2, Day 1 (< Median Cutpoint, n=20)Cycle 2, Day 1 (> = Median Cutpoint, n=20)Cycle 2, Day 28 (< Median Cutpoint, n=14)Cycle 2, Day 28 (> = Median Cutpoint, n=15)Cycle 3, Day 1 (< Median Cutpoint, n=10)Cycle 3, Day 1 (> = Median Cutpoint, n=11)Cycle 3, Day 28 (> = Median Cutpoint, n=6)Cycle 5, Day 28 (< Median Cutpoint, n=2)
Sunitinib15.811.015.812.430.811.116.816.132.916.132.938.3

[back to top]

Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline

TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionweeks (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=29)Cycle 1, Day 1 (> = Median Cutpoint, n=30)Cycle 1, Day 28 (< Median Cutpoint, n=23)Cycle 1, Day 28 (> = Median Cutpoint, n=23)Cycle 2, Day 1 (< Median Cutpoint, n=19)Cycle 2, Day 1 (> = Median Cutpoint, n=20)Cycle 2, Day 28 (< Median Cutpoint, n=15)Cycle 2, Day 28 (> = Median Cutpoint, n=15)Cycle 3, Day 1 (< Median Cutpoint, n=10)Cycle 3, Day 1 (> = Median Cutpoint, n=10)Cycle 3, Day 28 (> = Median Cutpoint, n=6)Cycle 5, Day 28 (> = Median Cutpoint, n=2)
Sunitinib16.110.315.811.013.116.110.831.816.830.832.937.0

[back to top]

Comparison of Kaplan-Meier TTP Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline Changes From Baseline

TTP = time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Interventionweeks (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=26)Cycle 1, Day 1 (> = Median Cutpoint, n=27)Cycle 1, Day 28 (< Median Cutpoint, n=17)Cycle 1, Day 28 (> = Median Cutpoint, n=17)Cycle 2, Day 1 (< Median Cutpoint, n=14)Cycle 2, Day 1 (> = Median Cutpoint, n=15)Cycle 2, Day 28 (< Median Cutpoint, n=11)Cycle 3, Day 1 (< Median Cutpoint, n=8)Cycle 3, Day 1 (> = Median Cutpoint n=8)Cycle 3, Day 28 (> = Median Cutpoint, n=4)
Sunitinib11.112.411.010.111.016.111.033.833.943.3

[back to top]

Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline

PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionweeks (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=29)Cycle 1, Day 1 (> = Median Cutpoint, n=30)Cycle 1, Day 28 (< Median Cutpoint, n=23)Cycle 1, Day 28 (> = Median Cutpoint, n=23)Cycle 2, Day 1 (< Median Cutpoint, n=19)Cycle 2, Day 1 (> = Median Cutpoint, n=20)Cycle 2, Day 28 (< Median Cutpoint, n=15)Cycle 2, Day 28 (> = Median Cutpoint, n=15)Cycle 3, Day 1 (< Median Cutpoint, n=10)Cycle 3, Day 1 (> = Median Cutpoint, n=10)Cycle 3, Day 28 (> = Median Cutpoint, n=6)Cycle 5, Day 28 (> = Median Cutpoint, n=2)
Sunitinib16.110.112.411.013.116.110.831.819.730.832.937.0

[back to top]

Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline

PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1) divided by 7.02. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point. (NCT00113516)
Timeframe: [Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Interventionweeks (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=26)Cycle 1, Day 1 (> = Median Cutpoint, n=27)Cycle 1, Day 28 (< Median Cutpoint, n=17)Cycle 1, Day 28 (> = Median Cutpoint, n=17)Cycle 2, Day 1 (< Median Cutpoint, n=14)Cycle 2, Day 1 (> = Median Cutpoint, n=15)Cycle 2, Day 28 (< Median Cutpoint, n=11)Cycle 3, Day 1 (< Median Cutpoint, n=8)Cycle 3, Day 1 (> = Median Cutpoint, n=8)Cycle 3, Day 28 (> = Median Cutpoint, n=4)
Sunitinib11.111.011.010.111.016.111.033.822.543.3

[back to top]

Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline Changes From Baseline

OS = time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death minus date of sunitinib first dose +1)divided by 30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after stratification by < or > = median changes from Baseline in VEGFR3 at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionmonths (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=30)Cycle 1, Day 1 (> = Median Cutpoint, n=30)Cycle 1, Day 28 (< Median Cutpoint, n=23)Cycle 1, Day 28 (> = Median Cutpoint, n=23)Cycle 2, Day 1 (< Median Cutpoint, n=20)Cycle 2, Day 1 (> = Median Cutpoint, n=20)Cycle 2, Day 28 (< Median Cutpoint, n=14)Cycle 2, Day 28 (> = Median Cutpoint, n=15)Cycle 3, Day 1 (> = Median Cutpoint, n=11)Cycle 3, Day 28 (< Median Cutpoint, n=6)Cycle 5, Day 28 (< Median Cutpoint, n=2)Cycle 5, Day 28 (> = Median Cutpoint, n=2)
Sunitinib8.76.114.77.113.78.811.213.37.417.717.113.8

[back to top]

Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of Soluble E-Selectin at Baseline and Changes From Baseline

OS=time from start of study treatment to death due to any cause. OS (in months) calculated as (date of death minus date of sunitinib first dose +1) divided by 30.4. For subjects not expiring their survival times were censored at last date of known contact they were known to be alive. Subjects lacking data beyond day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of soluble E-selectin at Baseline and after stratification by < or > = median changes from Baseline in soluble E-selectin at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Interventionmonths (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=26)Cycle 1, Day 1 (> = Median Cutpoint, n=27)Cycle 1, Day 28 (< Median Cutpoint, n=17)Cycle 1, Day 28 (> = Median Cutpoint, n=17)Cycle 2, Day 1 (< Median Cutpoint, n=14)Cycle 2, Day 1 (> = Median Cutpoint, n=15)Cycle 2, Day 28 (< Median Cutpoint, n=11)Cycle 2, Day 28 (> = Median Cutpoint, n=11)Cycle 3, Day 1 (> = Median Cutpoint, n=8)Cycle 3, Day 28 (> = Median Cutpoint, n=4)Cycle 5, Day 28 (> = Median Cutpoint, n=2)
Sunitinib6.58.08.76.511.28.58.014.812.715.313.8

[back to top] [back to top] [back to top]

VEGF-C Concentration at Baseline

Concentration of VEGF-C at baseline. (NCT00113516)
Timeframe: Baseline (Cycle 1, Day 1) of Part 2

Interventionpg/mL (Mean)
Sunitinib793.19

[back to top]

Vascular Endothelial Growth Factor Receptor 3 (VEGFR3) Concentration at Baseline

Concentration of VEGFR3 at baseline. (NCT00113516)
Timeframe: Baseline (Cycle 1, Day 1) of Part 2

Interventionpicograms (pg)/milliliter (mL) (Mean)
Sunitinib30382.83

[back to top]

Time to Tumor Progression (TTP)

TTP was defined as the time from start of study treatment to first documentation of objective disease progression. If tumor progression data included more than 1 date, the first date was used. TTP (in weeks) was calculated as (first event date - first paclitaxel/carboplatin dose date +1)/7.02. (NCT00113516)
Timeframe: From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib)

Interventionweeks (Median)
First Carboplatin Plus Paclitaxel, Then Sunitinib23.6

[back to top]

Soluble E-Selectin at Baseline

Concentration of soluble E-Selectin at baseline. (NCT00113516)
Timeframe: Baseline (Cycle 1, Day 1) of Part 2

Interventionnanograms (ng)/mL (Mean)
Sunitinib27.06

[back to top]

Proportion of Subjects Surviving at One Year

Proportion of those surviving at the end of one year from the first dose of study treatment. In the absence of confirmation of death, survival time was censored at the last date the subject was known to be alive. Patients lacking data beyond the day of first dose had their survival time censored at Day 1 of treatment. (NCT00113516)
Timeframe: From start of treatment until 1 year or death

Interventionproportion (Number)
First Carboplatin Plus Paclitaxel, Then Sunitinib0.405

[back to top]

Duration of Response (DR)

DR=time from the first documentation of objective tumor response (complete response [CR] or partial response [PR]) that was subsequently confirmed to first documentation of objective disease progression or death due to any cause, whichever was first. CR=disappearance of all target lesions. PR=a > = 30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. If tumor progression data included more than 1 date, first date was used. DR (in weeks) was calculated as (the end date for DR - first CR or PR that was subsequently confirmed +1)/7.02. (NCT00113516)
Timeframe: From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib) or death

Interventionweeks (Median)
First Carboplatin Plus Paclitaxel, Then Sunitinib27.3

[back to top]

Progression-free Survival (PFS)

PFS was defined as the time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date - first paclitaxel/carboplatin dose date +1)/7.02. (NCT00113516)
Timeframe: From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib) or death

Interventionweeks (Median)
First Carboplatin Plus Paclitaxel, Then Sunitinib23.1

[back to top]

VEGFR3 Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)

Median VEGFR3 concentration at each time point divided by median VEGFR3 concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionratio (Number)
Cycle 1, Day 28 (CR or PR or SD, n=16)Cycle 1, Day 28 (PD, n=20)Cycle 2, Day 1 (CR or PR or SD, n=19)Cycle 2, Day 1 (PD, n=16)Cycle 2, Day 28 (CR or PR or SD, n=15)Cycle 2, Day 28 (PD, n=12)Cycle 3, Day 1 (CR or PR or SD, n=15)Cycle 3, Day 1 (PD, n=5)Cycle 3, Day 28 (CR or PR or SD, n=11)Cycle 3, Day 28 (pd, n=1)Cycle 5, Day 28 (CR or PR or SD, n=4)
Sunitinib0.340.350.750.840.320.380.570.920.380.430.30

[back to top]

Dose-Corrected Ctrough of Sunitinib

Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included. (NCT00113516)
Timeframe: predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Interventionng/mL (Mean)
Cycle 1, Day 28 (n=39)Cycle 2, Day 28 (n=28)Cycle 3, Day 28 (n=13)Cycle 5, Day 28 (n=5)
Sunitinib64.1059.8549.5954.51

[back to top]

VEGF-C Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)

Median VEGF-C concentration at each time point divided by median VEGF-C concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionratio (Number)
Cycle 1, Day 28 (CR or PR or SD, n=16)Cycle 1, Day 28 (PD, n=20)Cycle 2, Day 1 (CR or PR or SD, n=18)Cycle 2, Day 1 (PD, n=16)Cycle 2, Day 28 (CR or PR or SD, n=16)Cycle 2, Day 28 (PD, n=12)Cycle 3, Day 1 (CR or PR or SD, n=14)Cycle 3, Day 1 (PD, n=5)Cycle 3, Day 28 (CR or PR or SD, n=11)Cycle 3, Day 28 (PD, n=1)Cycle 5, Day 28 (CR or PR or SD, n=4)
Sunitinib0.730.810.870.850.890.690.890.780.850.900.78

[back to top]

VEGF-C Ratio to Baseline at Each Time Point

VEGF-C concentration at each time point divided by VEGF-C concentration at baseline (ratio to baseline). (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionratio (Mean)
Cycle 1, Day 28 (n=46)Cycle 2, Day 1 (n=39)Cycle 2, Day 28 (n=30)Cycle 3, Day 1 (n=20)Cycle 3, Day 28 (n=12)Cycle 5, Day 28 (n=4)
Sunitinib0.810.900.911.000.910.89

[back to top]

VEGFR3 Ratio to Baseline at Each Time Point

VEGFR3 concentration at each time point divided by VEGFR3 concentration at baseline (ratio to baseline). (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionratio (Mean)
Cycle 1, Day 28 (n=46)Cycle 2, Day 1 (n=40)Cycle 2, Day 28 (n=29)Cycle 3, Day 1 (n=21)Cycle 3, Day 28 (n=12)Cycle 5, Day 28 (n=4)
Sunitinib0.390.740.360.700.310.31

[back to top]

VEGFR3 at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)

Median concentration of VEGFR3 at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality). (NCT00113516)
Timeframe: Baseline (Cycle 1, Day 1) of Part 2

Interventionpg/mL (Number)
Cycle 1, Day 1 (CR or PR or SD, n=21)Cycle 1, Day 1 (PD, n=24)
Sunitinib21660.0027740.00

[back to top]

Comparison of Kaplan-Meier OS Curves After Stratification by < or > = Median Levels of VEGF-C at Baseline and Changes From Baseline

OS = time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death minus date of sunitinib first dose +1) divided by 30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of sunitinib had their survival time censored at Day 1 of sunitinib treatment. Groups are defined by < or > = median levels of VEGF-C at Baseline and after stratification by < or > = median changes from Baseline in VEGF-C at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionmonths (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=29)Cycle 1, Day 1 (> = Median Cutpoint, n=30)Cycle 1, Day 28 (< Median Cutpoint, n=23)Cycle 1, Day 28 (> = Median Cutpoint, n=23)Cycle 2, Day 1 (< Median Cutpoint, n=19)Cycle 2, Day 1 (> = Median Cutpoint, n=20)Cycle 2, Day 28 (< Median Cutpoint, n=15)Cycle 2, Day 28 (> = Median Cutpoint, n=15)Cycle 3, Day 1 (< Median Cutpoint, n=10)Cycle 3, Day 1 (> = Median Cutpoint, n=10)Cycle 3, Day 28 (< Median Cutpoint, n=6)Cycle 5, Day 28 (< Median Cutpoint, n=2)Cycle 5, Day 28 (> = Median Cutpoint, n=2)
Sunitinib8.55.28.58.89.712.78.014.810.215.814.214.216.6

[back to top]

Trough Plasma Concentration (Ctrough) of Sunitinib

Ctrough = the plasma concentration prior to study drug administration. On Day 28, this parameter provided and idea of the concentration at steady state since no big fluctuation was expected in a 24 hour interval. (NCT00113516)
Timeframe: predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Interventionnanograms (ng)/milliliter (mL) (Mean)
Cycle 1, Day 28 (n=51)Cycle 2, Day 28 (n=36)Cycle 3, Day 28 (n=16)Cycle 5, Day 28 (n=6)
Sunitinib57.6950.8841.5538.57

[back to top]

Comparison of Kaplan-Meier PFS Curves After Stratification by < or > = Median Levels of VEGFR3 at Baseline and Changes From Baseline

PFS = time from start of study treatment to first documentation of objective disease progression or to death on study due to any cause, whichever was first. If tumor progression data included more than 1 date, the first date was used. PFS (in weeks) was calculated as (first event date minus first sunitinib dose date +1)divided by 7.02. Groups are defined by < or > = median levels of VEGFR3 at Baseline and after Stratification by < or > = median changes from Baseline in VEGFR3 at each time point. (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 5 (Day 28) of Part 2

Interventionweeks (Median)
Cycle 1, Day 1 (< Median Cutpoint, n=30)Cycle 1, Day 1 (> = Median Cutpoint, n=30)Cycle 1, Day 28 (< Median Cutpoint, n=23)Cycle 1, Day 28 (> = Median Cutpoint, n=23)Cycle 2, Day 1 (< Median Cutpoint, n=20)Cycle 2, Day 1 (> = Median Cutpoint, n=20)Cycle 2, Day 28 (< Median Cutpoint, n=14)Cycle 2, Day 28 (> = Median Cutpoint, n=15)Cycle 3, Day 1 (< Median Cutpoint, n=10)Cycle 3, Day 1 (> = Median Cutpoint, n=11)Cycle 3, Day 28 (> = Median Cutpoint, n=6)Cycle 5, Day 28 (< Median Cutpoint, n=2)
Sunitinib13.110.315.810.322.511.116.816.132.916.132.938.3

[back to top]

Soluble E-Selectin Ratio to Baseline at Each Time Point Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)

Median soluble E-selectin concentration at each time point divided by median soluble E-selectin concentration at baseline (ratio to baseline) for subjects with tumor response (CR or PR or [SD > = 6 weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a non-parametric test that makes no assumptions about the distribution of the data (eg, normality). (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Interventionratio (Number)
Cycle 1, Day 28 (CR or PR or SD, n=10)Cycle 1, Day 28 (PD, n=16)Cycle 2, Day 1 (CR or PR or SD, n=13)Cycle 2, Day 1 (PD, n=12)Cycle 2, Day 28 (CR or PR or SD, n=10)Cycle 2, Day 28 (PD, n=10)Cycle 3, Day 1 (CR or PR or SD, n=10)Cycle 3, Day 1 (PD, n=5)Cycle 3, Day 28 (CR or PR or SD, n=7)Cycle 3, Day 28 (PD, n=1)Cycle 4, Day 28 (CR or PR or SD, n=1)Cycle 5, Day 28 (CR or PR or SD, n=3)
Sunitinib0.840.840.840.760.860.640.740.770.670.781.130.64

[back to top]

Soluble E-Selectin Ratio to Baseline at Each Time Point

Soluble E-Selectin concentration at each time point divided by soluble E-Selectin concentration at baseline (ratio to baseline). (NCT00113516)
Timeframe: Baseline to Cycle 1 (Day 28), Cycle 2 (Days 1, 28), Cycle 3 (Days 1, 28), Cycle 4 (Day 28), Cycle 5 (Day 28) of Part 2

Interventionratio (Mean)
Cycle 1, Day 28 (n=34)Cycle 2, Day 1 (n=29)Cycle 2, Day 28 (n=22)Cycle 3, Day 1 (n=16)Cycle 3, Day 28 (n=8)Cycle 5, Day 28 (n=3)
Sunitinib0.830.890.770.810.690.76

[back to top]

Soluble E-Selectin at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)

Median concentration of soluble E-selectin at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality). (NCT00113516)
Timeframe: Baseline (Cycle 1, Day 1) of Part 2

Interventionpg/mL (Number)
Cycle 1, Day 1 (CR or PR or SD, n=17)Cycle 1, Day 1 (PD, n=21)
Sunitinib26.4027.40

[back to top]

Dose-Corrected Ctrough of Total Drug (Sunitinib + SU-012662)

Ctrough = the plasma concentration prior to study drug administration. Dose correction was made to the initial intended dose in Cycle 1. This was determined due to potential dose changes throughout the study in different subjects. It was calculated as the observed values multiplied by the reference dose (50 mg) divided by the actual dose. For dose-corrected trough concentration, only trough concentration values from subjects who received sunitinib during at least the last 10 consecutive days of dosing at the same dose level were included. (NCT00113516)
Timeframe: predose on Day 28 of Cycles 1, 2, 3, and 5 of Part 2

Interventionng/mL (Mean)
Cycle 1, Day 28 (n=39)Cycle 2, Day 28 (n=28)Cycle 3, Day 28 (n=13)Cycle 5, Day 28 (n=5)
Sunitinib92.0087.2270.2476.80

[back to top]

Number of Subjects With Overall Confirmed Objective Disease Response

Objective disease response = subjects with confirmed CR or PR according to the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.0). A CR was defined as the disappearance of all target lesions. A PR was defined as a ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. (NCT00113516)
Timeframe: From start of treatment until Day 21 of Cycles 2 and 4 (Carboplatin plus Paclitaxel), Day 28 of Cycles 1, 2, 3, 4, and even cycles thereafter (Sunitinib)

Interventionparticipants (Number)
First Carboplatin Plus Paclitaxel, Then Sunitinib23

[back to top]

Overall Survival (OS)

OS was defined as the time from start of study treatment to death due to any cause. OS (in months) was calculated as (date of death - date of paclitaxel/carboplatin first dose +1)/30.4. For subjects not expiring, their survival times were censored at the last date of known contact they were known to be alive. Subjects lacking data beyond the day of first dose of paclitaxel/carboplatin had their survival time censored at Day 1 of paclitaxel/carboplatin treatment. (NCT00113516)
Timeframe: From start of study treatment until death

Interventionmonths (Median)
First Carboplatin Plus Paclitaxel, Then Sunitinib10.4

[back to top]

VEGF-C at Baseline Stratified by Tumor Response (CR or PR or [SD > = 6 Weeks] or PD)

Median concentration of VEGF-C at baseline stratified by tumor response (CR or PR or [SD > = 6 Weeks] or PD). A measure of dispersion is not included because the Wilcoxon rank sum test is a nonparametric test that makes no assumptions about the distribution of the data (eg, normality). (NCT00113516)
Timeframe: Baseline (Cycle 1, Day 1) of Part 2

Interventionpg/mL (Number)
Cycle 1, Day 1 (CR or PR or SD, n=20)Cycle 1, Day 1 (PD, n=24)
Sunitinib704.80766.45

[back to top]

Number of Participants With Overall Tumor Response

"Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:~Complete Response (CR): disappearance of all target lesions;~Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;~Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions;~Stable Disease (SD): small changes that do not meet above criteria.~Overall tumor response is the total number of CR and PRs." (NCT00117962)
Timeframe: Duration of study until progression (up to 4 years)

Interventionparticipants (Number)
Std Tx + Pemetrexed37
Std Tx + Pemetrexed and Cetuximab38

[back to top]

18 Month Survival

Percentage of participants who were alive at 18 months. The 18 month survival, with 95% CI, was estimated using the Kaplan-Meier method. (NCT00117962)
Timeframe: 18 months (from randomization)

Interventionpercentage of participants (Number)
Std Tx + Pemetrexed58
Std Tx + Pemetrexed and Cetuximab54

[back to top]

Overall Survival

Overall survival (OS) is defined as the time from patient randomization (arm assignment) to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method. (NCT00117962)
Timeframe: Time from randomization to death (up to 4 years)

Interventionmonths (Median)
Std Tx + Pemetrexed21.2
Std Tx + Pemetrexed and Cetuximab25.2

[back to top]

Failure-free Survival

Failure-free survival (FFS) is the time from randomization to a failure event, defined as disease progression or death from any cause (which ever occurred first). The median FFS with 95% CI was estimated using the Kaplan-Meier method, (NCT00117962)
Timeframe: Time from randomization to failure (up to 4 years)

Interventionmonths (Median)
Std Tx + Pemetrexed12.6
Std Tx + Pemetrexed and Cetuximab12.3

[back to top]

Disease Control

The disease control rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response + Stable Disease as best overall response according to radiological assessments according to investigator (based on modified WHO criteria). (NCT00122460)
Timeframe: evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Interventionpercentage of participants (Number)
Cetuximab Plus Chemotherapy81.1
Chemotherapy Alone60.0

[back to top]

Duration of Response

"Time from first assessment of Complete Response or Partial Response to disease progression or death (within 60 days of last tumor assessment).~Patients without event are censored on the date of last tumor assessment. Tumor assessments based on modified WHO criteria." (NCT00122460)
Timeframe: time from first assessment of Complete Response or Partial Response to disease progression, death or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Interventionmonths (Median)
Cetuximab Plus Chemotherapy5.6
Chemotherapy Alone4.7

[back to top]

Overall Survival Time (OS)

Time from randomization to death. Patients without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier. (NCT00122460)
Timeframe: time from randomization to death or last day known to be alive, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Interventionmonths (Median)
Cetuximab Plus Chemotherapy10.1
Chemotherapy Alone7.4

[back to top]

Progression-free Survival Time (PFS)

"Duration from randomization until radiological progression according to investigator (based on modified World Health Organisation (WHO) criteria) or death due to any cause.~Only deaths within 60 days of last tumor assessment are considered. Patients without event are censored on the date of last tumor assessment." (NCT00122460)
Timeframe: time from randomization to disease progression, death or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Interventionmonths (Median)
Cetuximab Plus Chemotherapy5.6
Chemotherapy Alone3.3

[back to top]

Safety - Number of Patients Experiencing Any Adverse Event

Please refer to Adverse Events section for further details (NCT00122460)
Timeframe: time from first dose up to 30 after last dose of study treatment, reported between day of first dose of study treatment, 22 Dec 2004, until cut-off date 12 Mar 2007

Interventionparticipants (Number)
Cetuximab Plus Chemotherapy218
Chemotherapy Alone208

[back to top]

Time to Treatment Failure

"Time from randomization to date of the first occurrence of; progression, discontinuation of treatment due to progression or adverse event, start of new anticancer therapy, withdrawal of consent, or death (within 60 days of last tumor assessment).~Patients without event are censored on the date of last tumor assessment." (NCT00122460)
Timeframe: Time from randomization to treatment failure or last tumor assessment, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Interventionmonths (Median)
Cetuximab Plus Chemotherapy4.8
Chemotherapy Alone3.0

[back to top]

Quality of Life (QOL) Assessment European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 Global Health Status

Mean global health status scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a better QoL. (NCT00122460)
Timeframe: at baseline, day 1 of cycle 3, first 6-weekly evaluation following completion of chemotherapy, 6 & 12 months after randomization, reported between day of first patient randomised, 21 Dec 2004,until cut-off date, 12 Mar 2007

,
Interventionscores on a scale (Least Squares Mean)
At baselineAt cycle 3Month 6
Cetuximab Plus Chemotherapy50.7452.6855.30
Chemotherapy Alone45.1545.4842.49

[back to top]

Quality of Life Assessment (EORTC QLQ-C30) Social Functioning

Mean social functioning scores (EORTC QLQ-C30) against time for each treatment group. Scores were derived from mutually exclusive sets of items, with scale scores ranging from 0 to 100 after a linear transformation. Higher scores indicate a higher level of social functioning. (NCT00122460)
Timeframe: at baseline, day 1 of cycle 3, first 6-weekly evaluation following completion of chemotherapy, 6 & 12 months after randomization, reported between day of first patient randomised, 21 Dec 2004,until cut-off date, 12 Mar 2007

,
Interventionscores on a scale (Least Squares Mean)
At baselineAt cycle 3Month 6
Cetuximab Plus Chemotherapy62.1464.6461.27
Chemotherapy Alone62.0560.6765.72

[back to top]

Best Overall Response

The best overall response rate is defined as the percentage of subjects having achieved confirmed Complete Response + Partial Response as the best overall response according to radiological assessments according to investigator (based on modified WHO criteria). (NCT00122460)
Timeframe: evaluations were performed every 6 weeks until progression, reported between day of first patient randomised, 21 Dec 2004, until cut-off date 12 Mar 2007

Interventionpercentage of participants (Number)
Cetuximab Plus Chemotherapy35.6
Chemotherapy Alone19.5

[back to top]

Progression Free Survival With KRAS Mutation Status

Progression free survival is defined in previous outcome measures. GIven the small number of KRAS mutant participants, the analysis combines data from both arms. (NCT00126581)
Timeframe: Duration of study (up to 3 years)

Interventionmonths (Median)
Mutant4
Wild Type6.7

[back to top]

18 Weeks Progression Free Survival (PFS) Rate

"The product limit estimator developed by Kaplan Meier will be used to graphically describe progression free survival for patients randomized to each study arm.~The 18 week progression-free survival rate was defined as the proportion of patients that were alive progression-free 18 weeks after registration into the study. Disease progression was assessed per modified RECIST criteria, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, in either primary or nodal lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of new lesions. Kaplan-Meier estimate of 18-week progression-free survival was calculated." (NCT00126581)
Timeframe: At 18 weeks

Interventionpercentage of participants (Number)
Arm A: Erlotinib52
Arm B: Erlotinib/Carboplatin/Paclitaxel69

[back to top]

Overall Response Rate

"The proportion of patients who respond (completely or partially) to each combination regimen will be estimated. An exact binomial confidence interval will be computed for these estimates.~Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:~Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions" (NCT00126581)
Timeframe: Duration of Study (up to 3 years)

Interventionpercentage of participants (Number)
Arm A: Erlotinib35
Arm B: Erlotinib/Carboplatin/Paclitaxel46

[back to top]

Progression Free Survival (PFS) by Epidermal Growth Factor Receptor (EGFR) Mutation Status

"PFS was defined as the time from registration until disease progression or death, whichever occurs first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. Progression is defined as in the primary outcome measure.~EGFR mutations were performed at the Dana-Farber Cancer Institute using a sensitive heteroduplex method coupled with enzymatic digestion as previously reported (Janne PA, et al: A rapid and sensitive enzymatic method for epidermal growth factor receptor mutation screening. Clin Cancer Res 12:751-758, 2006). All positive findings were independently verified and subjected to sequencing. The mutation analyses were blinded to the participants' clinical outcome." (NCT00126581)
Timeframe: Duration of treatment (up to 3 years)

,
Interventionmonths (Median)
EGFR MutantEGFR Wild Type
Arm A: Erlotinib14.12.6
Arm B: Erlotinib/Carboplatin/Paclitaxel17.24.8

[back to top]

Overall Response Rate by EGFR Mutation Status

Response and EGFR mutation status are defined in previous outcome measures. (NCT00126581)
Timeframe: Duration of study (up to 3 years)

,
Interventionpercentage of participants (Number)
EGFR MutantEGFR Wild Type
Arm A: Erlotinib709
Arm B: Erlotinib/Carboplatin/Paclitaxel7330

[back to top]

Overall Survival

Overall survival (OS) is defined as the time from patient randomization (arm assignment) to death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method. (NCT00126581)
Timeframe: Time from randomization to death (up to 3 years)

Interventionmonths (Median)
Arm A: Erlotinib24.6
Arm B: Erlotinib/Carboplatin/Paclitaxel19.8

[back to top] [back to top]

Overall Response Rate With KRAS Mutational Status

Overall response is defined in previous outcome measures. GIven the small number of KRAS mutant participants in each treatment arm, the analysis combines data from both arms. (NCT00126581)
Timeframe: Duration of study (up to 3 years)

Interventionpercentage of participants (Number)
Mutant29
Wild Type42

[back to top]

Toxicity

Per CTCAE (Common Toxicity Criteria for Adverse Events) number of participants who experienced toxicity on the study (NCT00129727)
Timeframe: 60 months

InterventionParticipants (Number)
Phase II of Carboplatin, Pacitaxel, and Bevacizumab62

[back to top]

Response Rate (RECIST-1)

To estimate the objective response rate of carboplatin, paclitaxel, and bevacizumab. Evaluate toxicity. (NCT00129727)
Timeframe: 5 years

InterventionPercentage of Participants (Number)
Phase II of Carboplatin, Pacitaxel, and Bevacizumab76

[back to top]

PFS

Progression Free Survival: To examine the toxicity, estimate the objective response rate, and progression free survival measured in months of carboplatin, paclitaxel, and bevacizumab followed by single agent bevacizumab as consolidation for advanced mullerian cancer (NCT00129727)
Timeframe: Median PFS in months - up to 5 years

InterventionMonths (Median)
Phase II of Carboplatin, Pacitaxel, and Bevacizumab29.8

[back to top] [back to top]

Number of Participants With Adverse Events in Sequential Cohort Dose Escalation Study of AMG 531 Following Chemotherapy

Number of participants experiencing an adverse event (AE) or serious adverse event (SAE) during study treatment, possible or probable related to study drug. All toxicities graded using the Common Terminology Criteria for Adverse Events version 3.0. Participation has a maximum of 6 cycles of chemotherapy on the study. (NCT00147225)
Timeframe: Toxicity assessments with each dose level/cycle (21-28 day cycle) up to 6 cycles

,,,,,
Interventionparticipants (Number)
Adverse Events, Possible or ProbableSerious Adverse Events, Possible or ProbableTotal Adverse Events
1 mcg/kg AMG 531 Post Chemotherapy000
10 mcg/kg AMG 531 Post Chemotherapy112
10 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy808
10 mcg/kg Pre/Post Chemotherapy404
3 mcg/kg AMG 531 Post Chemotherapy000
5 mcg/kg AMG 531 Pre/Pre/Post/Post Chemotherapy527

[back to top]

Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b

(NCT00147537)
Timeframe: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)

Interventionmilligram/liter (mg/L) (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1.510
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)17.34
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)37.47
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)75.17
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)147.3
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)261.3
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)415.7
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)485.0

[back to top]

Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. (NCT00147537)
Timeframe: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)

InterventionDay (Median)
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)5.360
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)15.40

[back to top]

Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2

HAHA are indicators of immunogenicity to CP-751,871 (NCT00147537)
Timeframe: Day 1 pre-infusion of each Cycle (each cycle was 21 day) up to Cycle 17 and 150 days after the last CP-751,871 infusion

Interventionnumber of participants (Number)
CP-751,871 + Paclitaxel + Carboplatin (Phase 2)0
Paclitaxel + Carboplatin + Additional CP-751,871 (Phase 2)0

[back to top]

Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b

(NCT00147537)
Timeframe: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)

Interventionmg/L (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2.975
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)19.15
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)40.70
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)100.7
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)327.0
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)331.1
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)440.3
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)447.3

[back to top]

Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. (NCT00147537)
Timeframe: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)

InterventionDay (Mean)
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2.84
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)10.81
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)8.350
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)9.56
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)11.10
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)9.89

[back to top]

Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b

Maximum Observed Plasma Concentration (NCT00147537)
Timeframe: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is then end of Cycle 4)

Interventionmg/L (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2.975
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)20.25
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)40.70
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)100.7
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)327.0
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)369.1
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)611.3
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)535.5

[back to top]

Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b

Maximum Observed Plasma Concentration (NCT00147537)
Timeframe: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)

Interventionmg/L (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1.510
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)17.34
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)38.60
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)75.17
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)147.3
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)275.2
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)415.7
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)483.1

[back to top]

CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b

Concentration at 504 hours post dose (NCT00147537)
Timeframe: Cycle 5 pre-infusion (which is the end of Cycle 4)

Interventionmg/L (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)0.0000
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)0.4630
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)27.70
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)21.20
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)125.3
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)357.0
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)158.6

[back to top]

CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b

Concentration at 504 hours post dose (NCT00147537)
Timeframe: Cycle 2 pre-infusion (which is the end of Cycle 1)

Interventionmg/L (Mean)
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)0.1610
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)4.550
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)9.820
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)28.20
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)61.11
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)95.20
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)86.73

[back to top]

Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) (NCT00147537)
Timeframe: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)

Interventionmg.hr/L (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)16.60
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1235
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)5137
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)11350
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)25630
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)49260
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)71200
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)87680

[back to top]

Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b

Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) (NCT00147537)
Timeframe: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)

Interventionmg.hr/L (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)64.70
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2255
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2670
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)23400
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)70300
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)82930
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)116200
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)114000

[back to top]

Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b

The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity. (NCT00147537)
Timeframe: Start of treatment (baseline) up to the end of Cycle 1 (Day 21)

Interventionmg/kg (Number)
CP-751,871 + Paclitaxel + Carboplatin (Phase 1b)NA

[back to top]

Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b

HAHA are indicators of immunogenicity to CP-751,871. (NCT00147537)
Timeframe: Day 1 pre-infusion of each cycle up to Cycle 17 (each cycle was 21 day), 150 days after the last CP-751,871 infusion, and last follow up visit (one year post last study dose)

Interventionnumber of participants (Number)
CP-751,871 + Paclitaxel + Carboplatin (Phase 1b)1
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)0

[back to top]

Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 1b

AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) (NCT00147537)
Timeframe: Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)

Interventionmg.hr/L (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)77.60
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2410
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)23200
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)52500
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)94360
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)214000
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)133200

[back to top]

Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. (NCT00147537)
Timeframe: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Interventionpercentage of participants (Number)
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2)37.0

[back to top]

Objective Response Rate: Phase 1b

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. (NCT00147537)
Timeframe: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Interventionpercentage of participants (Number)
CP-751,871 + Paclitaxel + Carboplatin (Phase 1b)33.3
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)25.0

[back to top]

Objective Response Rate: Phase 2

Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. (NCT00147537)
Timeframe: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Interventionpercentage of participants (Number)
CP-751,871 + Paclitaxel + Carboplatin (Phase 2)37.4
Paclitaxel + Carboplatin (Phase 2)27.5

[back to top]

Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 1 in Phase 1b

AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) (NCT00147537)
Timeframe: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)

Interventionmilligram.hour/Liter (mg.hr/L) (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)22.30
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2011
CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b)5320
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)12810
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)30500
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)54650
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)79820
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)85240

[back to top]

Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b

AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time. (NCT00147537)
Timeframe: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)

Interventionmg.hr/L (Mean)
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1434
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)16750
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)41200
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)69180
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)12100
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)107400

[back to top]

Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b

Accumulation ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) (NCT00147537)
Timeframe: Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1). Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).

Interventionratio (Mean)
CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b)3.480
CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1.009
CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1.830
CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1.550
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b)1.984
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b)2.260
CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b)1.962

[back to top] [back to top]

Progression-Free Survival (PFS): Phase 2

Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]). (NCT00147537)
Timeframe: Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization

Interventionmonths (Median)
CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 2)4.4
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2)4.5
Paclitaxel + Carboplatin (Phase 2)4.3
CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2 NR)5.1

[back to top]

Pathological Complete Response After Preoperative Therapy With Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in Patients With HER-2 Positive Early Breast Cancer

Pathological Complete Response is defined as the complete disappearance of invasive tumor in the breast at the time of surgery (NCT00148668)
Timeframe: 12 weeks

Interventionpercentage of participants (Number)
Arm 117
Arm 231

[back to top]

Overall Survival

Overall survival is defined as the time from date of randomization until the date of death. (NCT00152477)
Timeframe: Up to 57 weeks

Interventionweeks (Median)
Carboplatin/Paclitaxel (Randomized Part II SjS)36.14
Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS)47.14
Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS)46.57
Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS)47.57

[back to top]

Time to Treatment Failure

Time to treatment failure (TTF) is defined as the time from date of randomization until the date of progression, death or, for subjects who discontinued treatment for toxicity reason, their last dosing date, whichever occurs first. (NCT00152477)
Timeframe: Up to 57 weeks

Interventionweeks (Median)
Carboplatin/Paclitaxel (Randomized Part II SjS)13.21
Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS)21.71
Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS)18.43
Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS)24.29

[back to top]

Tumor Response Rate (RR)

"Participants are evaluated for response using Response Evaluation Criteria in Solid Tumors (RECIST) (Therasse P et al; 2000). The tumor response rate is calculated as the total number of subjects whose best overall response is a complete response (CR)= disappearance of all target lesions; or a partial response (PR) = >=30 % decrease in the sum of the longest diameter of target lesions, divided by the number of randomized subjects (RS):~(CR + PR) / RS." (NCT00152477)
Timeframe: 24 weeks

,,,
Interventionpercentage of participants (Number)
Complete responderPartial responder
Carboplatin/Paclitaxel (Randomized Part II SjS)020
Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS)026.4
Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS)022.6
Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS)030.2

[back to top]

Progression Free Survival (PFS)

Progression free survival (PFS) is defined as time from date of randomization until the date progressive disease (PD) is first recorded or until death, whichever is first. (NCT00152477)
Timeframe: Up to 57 weeks

Interventionweeks (Median)
Carboplatin/Paclitaxel (Randomized Part II SjS)24.14
Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS)26.86
Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS)26.86
Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS)25.43

[back to top]

Time to Response

Time to response is defined as the time from the first dose of study therapy until measurement criteria are first met for complete response or partial response (whichever is recorded first). (NCT00152477)
Timeframe: Week 24

Interventionweeks (Median)
Carboplatin/Paclitaxel (Randomized Part II SjS)8.57
Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS)9.14
Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS)11.86
Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS)9.00

[back to top]

Duration of Overall Response

The duration of overall response is measured from the time measurement criteria are first met for complete response (CR) or partial response (PR), whichever is recorded first, until the first date of documented progressive disease or death. (NCT00152477)
Timeframe: Up to 57 weeks

Interventionweeks (Median)
Carboplatin/Paclitaxel (Randomized Part II SjS)21.14
Carboplatin/Paclitaxel/CDP791 (Randomized Part II SjS)21.14
Carboplatin/Paclitaxel/CDP791 10mg (Randomized Part II SS)21.14
Carboplatin/Paclitaxel/CDP791 20mg (Randomized Part II SjS)18.00

[back to top]

Response Rate to Induction Chemotherapy Prior to Definitive Therapy (Surgery or Radiation)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT00176254)
Timeframe: assessed pre-study and once between days 36-57

Interventionparticipants (Number)
Treatment Arm: Induction LDFRT and Chemotherapy32

[back to top]

5 Year Disease-specific Survival

Outcome is calculated from the time of enrollment to the time of death due to disease under study or survival to 5 years without death from disease under study, whichever occurs first.The 5-year rates of disease-specific survival were calculated using the Kaplan-Meier method. (NCT00176254)
Timeframe: 5 years

Interventionparticipants (Number)
Treatment Arm: Induction LDFRT and Chemotherapy26

[back to top]

5 Year Overall Survival Rates

(NCT00176254)
Timeframe: 5 years post study

Interventionparticipants (Number)
Treatment Arm: Induction LDFRT and Chemotherapy24

[back to top]

5 Year Progression Free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT00176254)
Timeframe: 5 years

Interventionparticipants (Number)
Treatment Arm: Induction LDFRT and Chemotherapy23

[back to top]

Frequency of Severe (>/= Grade 3) Toxicities

(NCT00176254)
Timeframe: assessed starting on day 1 through study day 58 or until toxicity resolves

Interventionadverse events (Number)
Treatment Arm: Induction LDFRT and Chemotherapy36

[back to top]

5-Year Overall Survival Rate

Estimated using the product-limit method of Kaplan and Meier. Patients who were still alive were censored at the date of last follow-up (NCT00182793)
Timeframe: From time of initial PBPC rescue until the date of death from any cause, assessed up to 5 years post treatment.

Interventionpercentage of participants (Median)
All Patients75

[back to top]

5-Year Relapse-free Survival Rate

Estimated using the product-limit method of Kaplan and Meier. Relapse defined as appearance of any new lesions during or after protocol treatment. Whenever possible, relapses should be documented histologically. (NCT00182793)
Timeframe: From time of initial PBPC rescue until death or disease recurrence (disease progression for patients with stage IV disease), whichever came first, up to 5 years post treatment

Interventionpercentage of participants (Median)
All Patients53

[back to top]

Ocular Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification

"To describe the 5-year ocular survival of eyes outcome of intraocular retinoblastoma with respect to the new classification of the American Joint Committee on Cancer (AJCC).~For AJCC staging, the patients were classified into 2 groups of early (AJCC=1, 1a or 1b) and advanced (AJCC=2, 2a, 2b, 3, 3a, 3b) retinoblastoma . The analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately" (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum A-Early Disease0.857
Stratum A-Advanced Disease0.500
Stratum B-Early Disease1.0
Stratum B-Advanced Disease0.719

[back to top]

Ocular Survival of Stratum B Patients Responding to Window Treatment

"To estimate the 5-year ocular survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.~Ocular survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of enucleation of advanced stage eye or date of last follow-up, for patients with two advanced stage eyes, the time to the first enucleation will be used for analysis. Ocular survival will be estimated using the method of Kaplan and Meier. Standard error is 5-year ocular survival" (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum B0.667

[back to top]

Ocular Survival of Stratum A Patients

"To estimate the 5-year ocular survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.~Ocular survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of enucleation of advanced stage eye or date of last follow-up, for patients with two advanced stage eyes, the time to the first enucleation will be used for analysis. Ocular survival will be estimated using the method of Kaplan and Meier." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum A0.688

[back to top]

Number of Participants With Change in Size of Pineal Gland

The MRI reports from bilateral patients were reviewed and data abstracted regarding pineal gland measurement and information about pineal cysts. The number of participants with change in pineal gland size is reported here. (NCT00186888)
Timeframe: From diagnosis through 6 years after last patient enrollment

InterventionParticipants (Count of Participants)
Prominent or mildly enlarged pineal glandsPineal growth over timeNo change in pineal gland size
Participants With Bilateral Retinoblastoma12823

[back to top]

Stratum B Response Rate of Early Stage Eyes to Window Therapy

To estimate the proportion of early stage eyes defined as Reese-Ellsworth Group I, II, or III eyes, that responded to 2 courses of window therapy which consisted of vincristine and topotecan (NCT00186888)
Timeframe: Six weeks post window therapy.

InterventionParticipants (Number)
Partial responseProgressive Disease / New lesionFailure due to Toxicity
Stratum B1101

[back to top]

Change in Parenting Stress Index (PSI)

The PSI is a commonly used measure of parenting stress. In 101 questions, the PSI delineates between stress as a function of child characteristics (e.g., adaptability, demandingness, mood; Child Domain) and stress as a function of parent characteristics (e.g., depression, sense of competence, social isolation; Parent Domain), as well as an overall stress score (Total Stress). Raw scores are calculated (normative means: Child Doman = 98.4; Parent Domain = 122.7; Total Stress Score = 221.1). This measure was given at all time points. Scores range from 131-320 for Total Stress, 69-188 for Parent Domain, and 50-145 for Child Domain, with higher scores indicative of greater stress (Total: >260; Parent: >153, Child: >122). (NCT00186888)
Timeframe: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years

,,,,,
Interventionunits on a scale (Mean)
Child DomainParent DomainOverall Total Stress
1 Year93.27105.84200.51
2 Years92.77105.84198.61
3 Years94.60105.92200.23
5 Years92.49102.74194.68
6 Months93.08101.56194.84
Baseline96.76109.38207.25

[back to top]

Ocular Survival of Eyes of Stratum B Patients

"To estimate the 5-year ocular survival of early stage eyes (R-E I-III) of patients with contralateral advanced disease treated with vincristine and topotecan.~Ocular survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of enucleation of advanced stage eye or date of last follow-up, for patients with two advanced stage eyes, the time to the first enucleation will be used for analysis. Ocular survival will be estimated using the method of Kaplan and Meier." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum B1.0

[back to top]

Ocular Survival of Eyes in Stratum B Patients Responding to Window Treatment

"To estimate the 5-year ocular survival of eye of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.~Ocular survival of eye will be defined per eye as the time interval from date on study to date of enucleation or date of last follow-up. Ocular survival of eye will be estimated using the method of Kaplan and Meier. Standard error is 5-year ocular survival." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum B0.763

[back to top]

Ocular Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification

"To describe the 5-year ocular survival of eyes outcome of intraocular retinoblastoma with respect to the new International Classification (IC) for Intraocular Retinoblastoma and the AJCC.~Patients were re-classified into 2 groups of early (IC groups A and B) and advanced (IC groups C, D, and E) retinoblastoma. Analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately.~Three eyes (2 patients) in stratum B received external beam radiation therapy (EBRT) and were also coincident with enucleation surgery, so their event status was not changed. Although the 3 eyes had shorter EFS interval because EBRT occurred (less than 2 years) before the surgery, it did not change the 5-year survival probability." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum A-Early Disease0.839
Stratum A-Advanced Disease0.667
Stratum B-Early Disease1.0
Stratum B-Advanced Disease0.743

[back to top]

Mean Primary Visual Cortex Function: Maximum T-value

"Functional magnetic resonance imagining (fMRI) was used to investigate primary visual cortex (V1) response to visual stimulation in 105 children being treated for intraocular retinoblastoma. Primary visual cortex activity was assessed in each subject using blood oxygenation level-dependent (BOLD) signal. The BOLD signal was analyzed via a general linear model using Statistical Parametric Mapping software (SPM, Wellcome Institute of Neurology, London). The maximum t-statistic in activated cluster (negative BOLD) is provided.~Voxel volume/peak BOLD response is a measurement of the volume of activation of the cortex. There is no known association with visual outcome at this time." (NCT00186888)
Timeframe: At diagnosis through 6 years after last patient enrollment

InterventionMaximum t-statistic (negative BOLD) (Mean)
Stratum A7.9
Stratum B6.2
Stratum C8.8

[back to top]

Mean Primary Visual Cortex Function: Cluster Size

"Functional magnetic resonance imagining (fMRI) was used to investigate primary visual cortex (V1) response to visual stimulation in 105 children being treated for intraocular retinoblastoma. Primary visual cortex activity was assessed in each subject using blood oxygenation level-dependent (BOLD) signal. The BOLD signal was analyzed via a general linear model using Statistical Parametric Mapping software (SPM, Wellcome Institute of Neuology, London).~Voxel volume/peak BOLD response is a measurement of the volume of activation of the cortex. There is no known association with visual outcome at this time." (NCT00186888)
Timeframe: At diagnosis through 6 years after last patient enrollment

Interventionnumber activated voxels (negative BOLD) (Mean)
Stratum A2372
Stratum B1080
Stratum C2105

[back to top]

Event-free Survival Per Eye in Stratum A and Stratum B Patients Based on AJCC Classification

"To describe the 5-year event-free survival of eyes outcome of intraocular retinoblastoma with respect to the new classification of the American Joint Committee on Cancer (AJCC).~For AJCC staging, the patients were re-classified into 2 groups of early (AJCC=1, 1a or 1b) and advanced (AJCC=2, 2a, 2b, 3, 3a, 3b) retinoblastoma. The analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately" (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum A-Early Disease0.857
Stratum A-Advanced Disease0.500
Stratum B-Early Disease1.0
Stratum B-Advanced Disease0.719

[back to top]

Event-free Survival of Stratum B Patients Responding to Window Treatment

"To estimate the 5-year event-free (EFS) survival of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.~Event-free survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) of advanced stage eyes, time to first event will be used for the analysis. Event-free survival will be estimated using the method of Kaplan and Meier." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum B0.667

[back to top]

Event-free Survival of Stratum A Patients

"To estimate the 5-year event-free survival of patients with early stage intraocular retinoblastoma (R-E I-III) with vincristine and carboplatin with intensive focal treatments.~Event-free survival will be defined per patient as follows: for patients with one advanced stage eye, the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) of advanced stage eyes, time to first event will be used for the analysis. Event-free survival will be estimated using the method of Kaplan and Meier." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum A0.688

[back to top]

Event-free Survival of Eyes in Stratum B Patients Responding to Window Treatment

"To estimate the 5-year event-free survival (EFS) of eyes of bilateral disease patients with advanced intraocular retinoblastoma in either eye (R-E IV-V) responding to the vincristine/topotecan window, with alternating cycles of vincristine and carboplatin with vincristine, topotecan, and periocular carboplatin, with intensive focal treatments.~Event-free survival of eye will be defined per eye as the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) or to last follow-up date for eyes without events. Event-free survival of eye will be estimated using the method of Kaplan and Meier. Standard error is 5-year EFS." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum B0.763

[back to top]

Event-free Survival of Eyes in Stratum A and Stratum B Patients Based on IC Classification

"To describe the 5-year event-free survival of the eyes outcome of intraocular retinoblastoma with respect to the new International Classification (IC) for Intraocular Retinoblastoma and the AJCC.~Patients were re-classified into 2 groups of early (IC groups A and B) and advanced (IC groups C, D, and E) retinoblastoma. Analysis was done at eye level since each eye in the same patient could be a different group. Patients from stratum A and B were analyzed separately.~Three eyes (2 patients) in stratum B received external beam radiation therapy (EBRT) and were also coincident with enucleation surgery, so their event status was not changed. Although the 3 eyes had shorter EFS interval because EBRT occurred (less than 2 years) before the surgery, it did not change the 5-year survival probability." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum A-Early Disease0.839
Stratum A-Advanced Disease0.667
Stratum B-Early Disease1.0
Stratum B-Advanced Disease0.743

[back to top]

Change in Relevant Daily Living Skills

The Adaptive Behavior composite was measured using the Vineland Scales of Adaptive Behavior (VABS) which is an examiner-administered semi-structured interview that assesses adaptive functioning from birth through adulthood. Subscales including motor skills, communication, socialization, and daily living skills combine into an overall adaptive behavior composite which is an age-normed standard score (normative mean = 100, SD = 15). This measure was given at all time points. Higher scores are indicative of better functioning, with scores from 85-115 in the average range. (NCT00186888)
Timeframe: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years

Interventionunits on a scale (Mean)
Baseline97.48
6 Months104.73
1 Year106.06
2 Years94.22
3 Years96.45
5 Years93.03

[back to top]

Change in Parent Report of Social-Emotional Factors

This outcome was measured using the Ages and Stages Questionnaire which is a parent-completed measure of a child's social-emotional functioning. Raw scores are calculated and compared to cut-off points by age (6 months = 45; 1 year = 48; 2 years = 50; 3 years = 59; 5 years =70). Higher scores are indicative of more problems with scores above the cut-off indicating significant concerns warranting additional follow-up. Possible scores range from 0 to 200+, depending on the number of items administered, which varies by the age of the child (19 to 33 items). However, the primary use of this tool is as a screener. Thus, typically, scores are interpreted as they compare to the identified cut-offs, with children who score above the cut-off referred for further evaluation. This measure was given at all time points. (NCT00186888)
Timeframe: Baseline (at study entry), 6 months, 1 year, 2 years, 3 years, and 5 years

Interventionunits on a scale (Mean)
Baseline40
6 Months19.42
1 Year26.28
2 Years29.67
3 Years40.61
5 Years39.93

[back to top]

Change in Cognitive Functioning

The Early Learning Composite was assessed with Mullen Scales of Early Learning, a measure of developmental functioning appropriate for use with children from birth through age 5. It is an examiner-administered instrument that uses toys, games, pictures, and other objects to elicit information about a child's language, fine and gross motor skills, and overall early learning capabilities. Raw scores are converted to an age-normed standard score (normative mean = 100, SD = 15) for the overall Early Learning Composite. This measure was given at all time points. Higher scores are indicative of better functioning, with scores from 85-115 in the average range. (NCT00186888)
Timeframe: Baseline (at study entry) and at ages 6 months, 1 year, 2 years, 3 years and 5 years

Interventionunits on a scale (Mean)
Baseline91.61
6 Months90.96
1 Year95.91
2 Years88.40
3 Years82.12
5 Years86.00

[back to top]

Stratum B Response to Window Therapy

The primary outcome is to estimate the proportion of stratum B patients responding to 2 courses of window therapy consisting of vincristine and topotecan. Complete Response is the complete regression of all apparent tumor masses in the funduscopic examination and by MRI and ultrasound (US). Partial Response is defined as greater than 50% (but less than 100%) reduction of the tumor masses in the funduscopic examination and by US and MRI, without the appearance of any new lesions. The response must persist for at least 4 weeks. Stratum A and C did not receive window therapy. (NCT00186888)
Timeframe: Six weeks post window therapy

InterventionParticipants (Number)
Partial responseProgressive Disease or New LesionFailure due to Toxicity
Stratum B2421

[back to top]

Relationship Between Topotecan Clearance (CL) and ABCG2/B1 Genotype in Stratum B Participants.

Blood samples for pharmacokinetic studies were collected at 0 hour (pre-dose), 5 minutes, 1.5 and 2.5 hours after the end of topotecan dose on Course 1 Day 1, Course 2 Day 1, and if further studies were needed, Course 5 Day 1 and Course 8 Day 1. A blood sample for pharmacogenetic studies was collected during the course of therapy on protocol. (NCT00186888)
Timeframe: Courses 1, 2, 5, and 8

InterventionLiters/hour/m^2 (Median)
Stratum B18.8

[back to top]

Relationship Between Topotecan Clearance (CL) and CYP3A4/5 Genotype in Stratum B Participants.

Blood samples for pharmacokinetic studies were collected at 0 hour (pre-dose), 5 minutes, 1.5 and 2.5 hours after the end of topotecan dose on Course 1 Day 1, Course 2 Day 1, and if further studies were needed, Course 5 Day 1 and Course 8 Day 1. A blood sample for pharmacogenetic studies was collected during the course of therapy on protocol. (NCT00186888)
Timeframe: Courses 1, 2, 5, and 8

InterventionLiters/hour/m^2 (Median)
Stratum B18.8

[back to top]

Number of Participants With Development of Pineal Cysts

The MRI reports from bilateral patients were reviewed and data abstracted regarding pineal gland measurement and information about pineal cysts. The number of participants with change in primary visual cortex function from diagnosis through 6 years after last patient enrollment is reported here. (NCT00186888)
Timeframe: At diagnosis through 6 years after last patient enrollment

InterventionParticipants (Count of Participants)
Developed new solitary cyst(s)Developed multiple new cystsGrowth of pineal cystDecrease in size (resolution) of pineal cystNo change
Participants With Bilateral Retinoblastoma12155111

[back to top]

Change in Distortion Product Otoacoustic Emissions (DPOAEs)

For DP_amplitude to be considered valid, a baseline DP_SNR (Distortion Product for Signal-to-noise ratio) for each frequency (1000-8000 Hz) and for each ear (left and right) must be = 6 dB. Any ear with invalid amplitude at baseline for each frequency should be excluded. The DPOAEs amplitude levels were averaged across the right and left ears at each frequency in the patients exhibiting valid DPOAE amplitudes in both ears, resulting in mean DPOAE levels. Subsequently, comparisons between baseline and most recent evaluation (collapsed across ears) for each frequency were made to evaluate if a significant decrease in DPOAE amplitude exists between the two time points. (NCT00186888)
Timeframe: From Diagnosis through 5 years after completion of therapy

,,
InterventiondB (Mean)
1000 Hz1400 Hz2000 Hz2800 Hz4000 Hz6000 Hz8000 Hz
Additional Evaluation4.58.211.08.43.45.7-9.9
Baseline17.716.615.111.615.313.35.0
Interim Evaluation5.59.413.012.211.312.9-2.0

[back to top]

Event-free Survival of Eyes of Stratum B Patients

"To estimate the 5-year event-free survival of early stage eyes (R-E I-III) of patients with contralateral advanced disease treated with vincristine and topotecan.~Event-free survival of eye will be defined per eye as the time interval from date on study to date of first event (an event includes external beam radiation or enucleation) or to last follow-up date for eyes without events. Event-free survival of eye will be estimated using the method of Kaplan and Meier." (NCT00186888)
Timeframe: From date on-study to an event or last follow-up

Interventionprobability (Number)
Stratum B1.0

[back to top]

Assessment of School Readiness

The Bracken Basic Concepts Scale was used to assess school readiness. It is an examiner-administered measure that assesses per-academic skills including letter and number recognition, shapes, colors, and understanding of sizes and comparisons. Raw scores are converted into age-normed scaled scores (normative mean = 10, SD = 3) for the School Readiness Composite. Higher scores are indicative of stronger pre-academic skills, with scores from 7 to 13 within the Average range. (NCT00186888)
Timeframe: Patients were assessed at 5 years of age

Interventionunits on a scale (Mean)
5 Years8.96

[back to top] [back to top]

Time to Disease Progression (TTP)

If a patient is lost to follow-up, the patient will be censored as of the last date of contact. Patients who start a new treatment before they progress will be censored as of the date of start of the new treatment. If a patient died due to reason other than study disease, and patient has not progressed or received any new treatment, TTP is censored at the date of death. (NCT00191451)
Timeframe: randomization date to the earliest date of the first documented disease progression date or the date of death if the patient dies due to study disease (up to 3.5 years)

Interventionmonths (Median)
HER2+7.2
HER2- (Taxane-)5.6
HER2- (Taxane+)4.6

[back to top]

Overall Tumor Response

Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. (NCT00191451)
Timeframe: baseline to disease progression/recurrence (up to 3.5 years)

,,
Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Not Evaluable (NE)
HER2- (Taxane-)01320122
HER2- (Taxane+)11513171
HER2+6261242

[back to top]

Percentage of Patients With Overall Survival at 1 Year and 2 Years

Kaplan-Meier estimates of overall survival (percentage of patients surviving) at 1 year and 2 years. (NCT00191451)
Timeframe: 1 Year, 2 Years

,,
Interventionpercentage of participants (Number)
1 Year Overall Survival2 Year Overall Survival
HER2- (Taxane-)67.541.4
HER2- (Taxane+)47.820.5
HER2+90.073.3

[back to top]

Duration of Response

Among tumor responders, the duration of tumor response is measured from the date of response (complete response [CR] or partial response [PR]) until the first date of documented progression or death from any cause. Duration of tumor response will be censored at the date of the last follow-up visit for tumor responders who are still alive and who have not progressed. (NCT00191451)
Timeframe: date of response (CR or PR) until the first date of documented progression or death from any cause (up to 3.5 years)

Interventionmonths (Median)
HER2+6.9
HER2- (Taxane-)6.4
HER2- (Taxane+)5.6

[back to top]

Number of Patients Who Experienced Alopecia

(NCT00191451)
Timeframe: Baseline to 3.5 years

Interventionparticipants (Number)
HER2+21
HER2- (Taxane-)17
HER2- (Taxane+)16

[back to top]

Time to Treatment Failure

Time to treatment failure was defined as the duration from date of randomization to the date of the first of the following events: early discontinuation of study therapy; progression of disease, or death due to any cause. Time to treatment failure will be censored at the date of the last follow-up visit for participants who did not discontinue early, who are still alive, and who have not progressed. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies. (NCT00191646)
Timeframe: Baseline to stopping treatment up to 82 months

Interventionmonths (Median)
Gemcitabine/Carboplatin13.0
Paclitaxel/Carboplatin13.1

[back to top]

Proportion of Participants With Response (Response Rate)

Response rate (RR) = proportion of participants with best overall Complete Response (CR: disappearance of all target lesions [TL]) or Partial Response (PR: 30% decrease in sum of longest diameter of TL). Induction therapy RR = number of participants with CR or PR during induction divided by number of participants with measurable disease at baseline (TL measurement during screening). Crossover therapy RR = number of participants with CR or PR during crossover divided by number of participants with measurable disease at baseline (latest TL measurement by first dose date of crossover therapy). (NCT00191646)
Timeframe: Baseline to measured progressive disease up to 82 months

Interventionproportion of responders (Mean)
Gemcitabine/Carboplatin (Induction)0.676
Paclitaxel/Carboplatin (Induction)0.711
Gemcitabine (Crossover)0.357
Paclitaxel (Crossover)0.303

[back to top]

Progression Free Survival (PFS)

Progression free survival was defined as the duration from the date of randomization to the first date of documented disease progression or death from any cause. Tumor assessments were performed every three 21-day cycles during induction and crossover. Progression free survival was censored at the date of the last follow-up visit for participants who were still alive and who had not progressed. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies. (NCT00191646)
Timeframe: Baseline to measured progressive disease or death up to 82 months

InterventionMonths (Median)
Gemcitabine/Carboplatin20.0
Paclitaxel/Carboplatin22.2

[back to top]

Overall Survival

Overall survival is defined as the duration from baseline to death. For participants who are still alive at the data cut-off date, survival will be censored at the last contact date. Results are presented as a comparison between the two study treatment sequences (induction therapy followed by elective consolidation or crossover therapy) rather than the two induction therapies. (NCT00191646)
Timeframe: Baseline to death from any cause up to 82 months

Interventionmonths (Median)
Gemcitabine/Carboplatin43.8
Paclitaxel/Carboplatin57.3

[back to top]

Overall Survival

Overall survival time is defined as the time from the date of randomization to date of death due to any cause. Survival time is censored at the date of last contact for patients who are still alive or lost to follow-up. (NCT00191854)
Timeframe: baseline to date of death from any cause (up to 34 months)

Interventionmonths (Median)
Gemcitabine + Paclitaxel15.5
Gemcitabine + Carboplatin22.8
Gemcitabine + Cisplatin20.1

[back to top]

Progression Free Survival (PFS)

PFS was defined as the time from randomizaton to the date of documented disease progression or death on study, whichever occurred first. PFS for participants who discontinued from the study or who had not progressed at the time of analysis were treated as censored at the date of the last tumor assessment. (NCT00191854)
Timeframe: baseline to measured progressive disease or death (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death, or up to 24 months after randomization)

Interventionmonths (Median)
Gemcitabine + Paclitaxel4.8
Gemcitabine + Carboplatin4.3
Gemcitabine + Cisplatin4.8

[back to top]

Best Overall Response

Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. (NCT00191854)
Timeframe: baseline to measured progressive disease (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death or up to 24 months after randomization)

,,
Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Early Death from Other CausesUnknown
Gemcitabine + Carboplatin08251121
Gemcitabine + Cisplatin17291103
Gemcitabine + Paclitaxel112171414

[back to top]

Number of Participants With a Time to Treatment Failure (TTTF) Event

TTTF event was defined as documented disease progression, death on study, start of non-protocol-specified anticancer therapy, or therapy discontinuation due to toxicity. TTTF for patients who were still participating in study without treatment failure at time of analysis were treated as censored at date of last tumor assessment. TTTF for patients who had discontinued from therapy for reasons other than toxicity and who did not experience treatment failure prior to therapy discontinuation were treated as censored on day of study discontinuation. (NCT00191854)
Timeframe: randomization to date of documented disease progression, death on study, start of non-protocol-specified anticancer therapy, or therapy discontinuation due to toxicity, whichever occurred first (up to 6 months)

Interventionparticipants (Number)
Gemcitabine + Paclitaxel15
Gemcitabine + Carboplatin21
Gemcitabine + Cisplatin21

[back to top]

Duration of Response

Duration of response was measured from time of first documentation of complete response (disappearance of all target lesions) or partial response (30% decrease in sum of longest diameter of target lesions), until date of PFS. Duration of response was censored on day of last tumor assessment for patients who had not progressed or who had discontinued study at time of analysis, and for cases where investigator determined patient had progressive disease and discontinued study therapy and/or started a new, non-protocol-specified anti-cancer therapy before documented disease progression. (NCT00191854)
Timeframe: time of response to progressive disease or death (tumor assessments were performed every 4 cycles during study therapy, or 3 months during post-therapy until disease progression, death, or up to 24 months after randomization)

Interventionmonths (Median)
Gemcitabine + Paclitaxel5.8
Gemcitabine + Carboplatin3.2
Gemcitabine + Cisplatin5.1

[back to top]

Number of Grade 3/4 Toxicities Patients Experienced on Maintenance Bevacizumab Following Chemoradiation for Limited Stage - Small Cell Lung Cancer (LS-SCLC)

Toxicity was evaluated in all patients who received at least 1 dose of therapy, and graded according to CTCAE v. 3. (NCT00193375)
Timeframe: 18 months

InterventionGrade 3/4 Toxicity Events (Number)
HemorrhageDiarrheaFatigueHypertensionNauseaInfection - Other (Pnemonia)Pulmonary toxicitiesLeukopeniaNeutropeniaThrombocytopenia
Intervention2111144211

[back to top]

Overall Response Rate

Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters. (NCT00193375)
Timeframe: 18 month

Interventionpercentage of participants (Number)
Intervention80

[back to top]

2-Year Progression-free Survival (PFS)

Progression-free survival (PFS) was defined as the date of study entry until the date of tumor progression or death. 2-Year PFS is the percentage of patients alive and without progressive disease (PD) 2 years from the date of study entry. (NCT00193375)
Timeframe: 24 months

Interventionpercentage of participants (Number)
Intervention22

[back to top]

Pathologic Complete Response Rate

A pathological complete response (pCR) was defined as having no residual cancer at the primary site or in regional lymph nodes on pathologic review. (NCT00193427)
Timeframe: 18 months

InterventionPercentage of participants (Number)
Intervention0

[back to top]

Progression Free Survival (PFS)

Progression-free survival was calculated as the elapsed time between the date of study registration and the date of recurrence or death from any cause. (NCT00193427)
Timeframe: 19 months

InterventionMonths (Median)
Intervention9.9

[back to top]

Overall Survival (OS)

Overall survival was calculated as the elapsed time bewteen date of study registration and the date of death. (NCT00193427)
Timeframe: 18 months

InterventionMonths (Median)
Intervention18

[back to top]

Overall Response Rate (ORR)

Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters. (NCT00193427)
Timeframe: 18 months

Interventionpercentage of participants (Number)
Intervention30

[back to top]

Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease

Length of time, in months, that patients were alive from their first date of protocol treatment until worsening of their disease (NCT00193596)
Timeframe: 12 months

Interventionmonths (Median)
Paclitaxel/Carboplatin/Etoposide/Gefitinib3.3
Irinotecan/Gemcitabine/Gefitinib5.3

[back to top]

Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

Length of time, in months, that patients were alive from their first date of protocol treatment until death. (NCT00193596)
Timeframe: 24 months

Interventionmonths (Median)
Paclitaxel/Carboplatin/Etoposide/Gefitinib7.4
Irinotecan/Gemcitabine/Gefitinib8.5

[back to top]

Maximum Tolerated Dose in Phase I Portion of Study

Determine the maximum tolerated dose of the triplet combination of capecitabine that can be administered in combination with weekly paclitaxel and every four weeks carboplatin. (NCT00201734)
Timeframe: Every 3 weeks, for up to 24 weeks

Interventionmg/m2 (Number)
Phase I Patients750

[back to top]

Phase I: To Determine Side Effects

The common clinically significant grade 3 and 4 toxicities graded using the National Cancer Institutes Common Toxicity Criteria version 3.0 (NCT00201734)
Timeframe: Every 3 weeks, for up to 24 weeks

,
Interventionpercent of patients (Number)
NeutropeniaThrombocytopeniaFatigue
Phase I867276
Phase II727284

[back to top]

Time to Tumor Progression for Patients

For patients enrolled on the Phase II portion of the trial the time to progression was measured as the time from when the patient started treatment to the time the patient is first recorded as having disease progression or the date of death if the patient dies due to causes other than disease progression. (NCT00201734)
Timeframe: Up to 6 years

Interventionmonths (Median)
Phase II5.5

[back to top]

Progression-Free Survival at 6 Months for Patients

For patients enrolled on the Phase II portion of the trial Progression Free Survival (PFS) was measured from the percentage of patients that were still alive, without evidence of disease progression for 6 months following the initiation of treatment. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT00201734)
Timeframe: up to 6 years

Interventionpercent of patients (Number)
Phase II38

[back to top]

Objective Response Rate (ORR) for the Phase II Portion of the Study. CR+PR Per RECIST v1.0 Criteria Using a Single Arm , Two Stage Minimax Design.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT00201734)
Timeframe: Every 3 weeks, for up to 24 weeks

Interventionpercent of patients (Number)
Phase I21
Phase II32

[back to top]

One Year Survival for Patients

For patients enrolled on the Phase II portion of the trial the One-year survival was measured as the percentage of patients alive 1 year after their treatment in the trial. (NCT00201734)
Timeframe: Up to 1 year

Interventionpercent of patients (Number)
Phase II44

[back to top]

Overall Survival (OS)

Median Overall Survival of Participants. OS and Progression Free Survival (PFS) probabilities were estimated using the Kaplan-Meier method. For statistical purposes, it is important to note that this trial was not designed to compare outcomes among patients assigned to the different chemotherapies, but rather that molecular analysis directed individualized chemotherapy assignment is feasible and yields promising results in outcomes. (NCT00215930)
Timeframe: 24 Months

InterventionMonths (Median)
Double Agent Chemotherapy13.3

[back to top]

Best Disease Response After a Maximum of Six Cycles.

Determine the number of participants for each category of response rates (RR) in newly diagnosed patients with advanced non-small cell lung cancer (NSCLC) who are treated with a chemotherapeutic regimen assigned to them on the basis of expression of the genes ribonucleotide reductase subunit 1 (ERCC1) and excision repair cross-complementing group 1 gene (RRM1) expression. Prior to treatment we measured the level of ERCC1 and RRM1 expression in the patients tumor, on the basis of which the patient would be assigned a specific doublet chemotherapy. (NCT00215930)
Timeframe: 24 Months

InterventionParticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Not Assessible
Double Agent Chemotherapy0232361

[back to top]

Progression Free Survival (PFS)

PFS was recorded as the time elapsed from the date of first treatment to the date of first evidence for disease progression or death. OS and PFS probabilities were estimated using the Kaplan-Meier method. For statistical purposes, it is important to note that this trial was not designed to compare outcomes among patients assigned to the different chemotherapies, but rather that molecular analysis directed individualized chemotherapy assignment is feasible and yields promising results in outcomes. (NCT00215930)
Timeframe: 24 Months

InterventionMonths (Median)
Double Agent Chemotherapy6.6

[back to top]

Number of Participants Whose Response Allowed Them to Proceed to Chemoradiation

Response Rates - Complete Response (CR) + Partial Response (PR): We determined the number of participants whose response (both CT and PET assessment) to two cycles of induction chemotherapy with gemcitabine and carboplatin allowed them to proceed to chemoradiation. Response was evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. (NCT00226590)
Timeframe: Ranging from 2 weeks up to 4 years, 9 months

Interventionparticipants (Number)
Induction Therapy38

[back to top]

Progression Free Survival

To determine median Progression Free Survival rate. Progression-free survival (PFS) is defined as the interval between the date of the first chemotherapy administration and the date of objective progression or death. Progression was evaluated using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. (NCT00226590)
Timeframe: Ranging from 2 weeks up to 4 years, 9 months

Interventionmonths (Median)
Combination Therapy22.7

[back to top]

Treatment Completion

The number of participants who completed all treatment on schedule without dose reductions or delays. (NCT00226590)
Timeframe: Ranging from 2 weeks up to 4 years, 9 months

Interventionparticipants (Number)
Combination Therapy19

[back to top]

Overall Survival

To determine median Overall Survival rate (NCT00226590)
Timeframe: Ranging from 2 weeks up to 4 years, 9 months

Interventionmonths (Median)
Combination Therapy14.3

[back to top]

"To Evaluate the Toxicity and Tolerability of Pelvic Radiation Sandwiched Between Cycles of Paclitaxel/Carboplatin Chemotherapy in Patients With UPSC"

"Overall survival analysis of early stage (stage 1 & 2) and late stage (stage 3 & 4)UPSC patients who were prescribed radiation sanwhiched between three cycles of paclitaxel/platinum chemotherapy before and after RT. Outcome measures were Progression Free Survival (PFS) and Overall Survival (OS)." (NCT00231868)
Timeframe: Up to 7 years

Interventionmonths (Mean)
Early stage (PFS)Late stage (PFS)Early stage (OS)Late stage (OS)
Drug:Carboplatin, Paclitaxel & Radiation65.525.876.535.9

[back to top]

Safety and Tolerability

the number of patients with grade 4 (severe) toxicities and or hospitalizations were measured to assess safety and tolerability (NCT00232479)
Timeframe: from the first dose of chemotherapy until surgery which was approximately 16 weeks.

Interventionparticipants (Number)
Group 11

[back to top]

Number of Patients With Pathologic Complete Response (pCR)

pCR is defined as the absence of invasive tumor from the surgical specimen of breast and axilla which is obtained after the chemotherapy regimen has been delivered. (NCT00232479)
Timeframe: determined at the time of surgery which is approximately 16 weeks from the beginning of treatment

Interventionparticipants (Number)
Group 119

[back to top]

Overall Disease Response Rate

Overall response rate of single agent cetuximab and cetuximab + carboplatin will be measured by radiographic response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria every 8 weeks until subject experiences disease progression. Overall response will be measured as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD).Per RECIST v1.0 for target lesions and assessed by CT (spiral): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression (NCT00232505)
Timeframe: 5 years

,,,
InterventionParticipants (Count of Participants)
Complete responsePartial responseStable diseaseStable disease > 6 monthsProgressive diseaseNot evaluable
Cetuximab0231260
Cetuximab and Carboplatin1111510386
Cetuximab and Carboplatin After Cetuximab Alone0473122
Cetuximab and Carboplatin Subset11787323

[back to top]

Progression-Free Survival

Time to disease progression of cetuximab or cetuximab + carboplatin as indicated by radiographic assessment (NCT00232505)
Timeframe: Every four months until progression, death of any cause, or end of data collection up to 40 months

,
Interventionparticipants (Number)
Baseline4 months8 months12 months16 months20 months24 months28 months32 months36 months40 months
Cetuximab314221111110
Cetuximab and Carboplatin71271177661110

[back to top]

Overall Survival

Subjects will be contacted every 4 months after discontinuation of active treatment to assess survival. (NCT00232505)
Timeframe: Every four months until death of any cause or end of data collection up to 40 months

,
Interventionparticipants surviving (Number)
Baseline4 months8 months12 months16 months20 months24 months28 months32 months36 months40 months
Cetuximab31221298865110
Cetuximab and Carboplatin71564130231984320

[back to top]

Overall Survival Rate at 6, 12, 18, and 24 Months

"Overall Survival (OS) Rate of carboplatin, pemetrexed and bevacizumab combination treatment will be defined as the percentage of patients with documentation of status of alive at the following timepoints from registration to the study:~6 months 12 months 18 months 24 months" (NCT00234052)
Timeframe: 6, 12,18, and 24 months from treatment initiation

Interventionpercentage of patients alive (Number)
6 Months12 Months18 Months24 Months
Treatment With Carboplatin + Pemetrexed + Bevacizumab86613826

[back to top]

Overall Survival Rate

Overall Survival (OS) Rate of carboplatin, pemetrexed and bevacizumab combination treatment is defined from the time of registration to the study until death from any cause. Patients that are lost to follow up will be censored from last documentation of survival status. (NCT00234052)
Timeframe: During treatment and then every 3 months x 2 years, then every 6 months x 3 years or until death.

InterventionMonths (Median)
Treatment With Carboplatin + Pemetrexed + Bevacizumab14.1

[back to top]

Toxicity of Carboplatin, Pemetrexed and Bevacizumab Combination Treatment

"To characterize the toxicity profile of carboplatin, pemetrexed and bevacizumab combination treatment.~Toxicity data will be collected from initiation of treatment, every cycle, until 30 days post last treatment. Adverse events will be graded according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). Only toxicity determined to be a least possibility related to at least one study drug and grade 3 or 4 was collected for this outcome measure.~In general adverse events (AEs) will be graded according to the following:~Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE" (NCT00234052)
Timeframe: From treatment initiation, at the beginning of each cycle where one cycle equals 21 days until 30 days post treatment (range of cycles 1-51)

InterventionParticipants (Count of Participants)
AnemiaThrombocytopeniaNeutropeniaVenous ThrombosisFatigueDiverticulitisInfectionProteinuriaArterial ThrombosisIncreased Creatinine Levels
Treatment With Carboplatin + Pemetrexed + Bevacizumab3423445111

[back to top]

Duration of Response

Duration of Response for patients treated with the combination of carboplatin, pemetrexed and bevacizumab is measured from the time measurement criteria are met for Complete Response or Partial Response (whichever is first recorded) until the first date of documented progressive disease. (NCT00234052)
Timeframe: From documentation of response, every two cycles (1 cycle = 21 days) until progressive disease with range of cycles completed 1-51.

InterventionMonths (Median)
Treatment With Carboplatin + Pemetrexed + Bevacizumab7.7

[back to top]

Overall Response Rate

"Overall Response Rate (ORR) of patients treated with carboplatin, pemetrexed, and bevacizumab combination is defined as the number of patients who's best response is a Complete Response (CR) plus Partial Response (PR)as recorded from the start of treatment until disease progression as assessed by RECIST 1.0.~CR=Disappearance of all target lesions for a minimum of 4 weeks. PR=At least a 30% decrease in the sum of the longest diameter (LD) of target lesions for a minimum of 4 weeks, taking as reference the baseline sum LD. No simultaneous increase in the size of any lesion or the appearance of a new lesion may occur." (NCT00234052)
Timeframe: Every two cycles until disease progression. Median follow up of 13 months (range 0.8 to 34.4 months)

InterventionParticipants (Count of Participants)
Treatment With Carboplatin + Pemetrexed + Bevacizumab27

[back to top]

Median Progression Free Survival

Progression Free Survival (PFS) in patients treated with the combination of carboplatin, pemetrexed and bevacizumab is defined as the time from registration to the time of documented disease progression or death from any cause. Patients that were lost to follow up or withdrew consent were censored at that point. (NCT00234052)
Timeframe: Approximately every 3 weeks until disease progression or death. Median follow up of 13 months (range 0.8 to 34.4 months)

InterventionMonths (Median)
Treatment With Carboplatin + Pemetrexed + Bevacizumab7.8

[back to top]

Progression Free Survival at 6, 12, 18, 24 Months

"Progression Free Survival (PFS) Rate of carboplatin, pemetrexed and bevacizumab combination treatment is defined as the percentage of patients without progression at the following time points from registration to the study:~6 months 12 months 18 months 24 months." (NCT00234052)
Timeframe: 6, 12,18, and 24 months from treatment initiation

Interventionpercentage of patients with PFS (Number)
6 Months12 Months18 Months24 Months
Treatment With Carboplatin + Pemetrexed + Bevacizumab59342719

[back to top]

Change in Standard Uptake Value (SUVmax) on Positron Emission Tomography (PET) Scans Pre and Post Chemotherapy and Radiation in This Trial and Ability to Predict Surgical Resection Rate, Progression-free Survival and 2 Year Overall Survival

The change in standardized uptake values (SUV)max on PET scans obtained pre- and after 5 weeks of combined chemo-radiation for patients enrolled on the trial were evaluated for ability to predict outcomes including complete resection at time of surgery (3-6 weeks after completion of the chemo-radiation), progression-free survival and 2 year overall survival. The mean SUVmax pre chemoradiation minus the mean SUVmax post-radiation is reported. (NCT00238615)
Timeframe: baseline, 5 weeks after combined chemo-radiation

Interventionstandardized uptake value (SUV)max (Mean)
Docetaxel / Carboplatin / XRT + Surgical Resection5.7

[back to top]

2 Year Overall Survival After a Combination of Chemotherapy, Radiation and Surgery in Stage III NSCLC Patients Following the Protocol Therapy.

Patients were analyzed for 2 year overall survival after receiving trimodality (chemotherapy/radiation/surgery) therapy for stage III NSCLC. Patients had a chest x-ray and a doctor visit with a physical examination every 3 months after completion of all therapy for 3 years then every 6 months for 3 years to look for evidence of recurrent disease and to follow survival. Thoracic computed tomography (CT) scans were obtained at 6, 12, 18 months after completion of all therapy and then yearly for 3 years or as clinically indicated to evaluate for relapse. (NCT00238615)
Timeframe: Two years

Interventionparticipants (Number)
Docetaxel+Carboplatin +Radiation+Surgery7

[back to top]

Objective Response Rate (Part I)

The primary objective is to determine the objective tumor response rate of sequential topoisomerase targeting with irinotecan/oxaliplatin followed by etoposide/carboplatin in chemotherapy-naïve patients with extensive SCLC and Stage IIIb (wet) - IV Large Cell Carcinoma of the Lung with neuroendocrine markers. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. Stable response means did not meet criteria for progressive or partical response. 20% progressive disease. (NCT00240097)
Timeframe: baseline to 18 months

InterventionParticipants (Number)
Complete responsePartial responseStable diseaseProgressive diseaseUnevaluable
Regimen A and B420101

[back to top]

Progression Free Survival (Part I)

Time to progressive disease (NCT00240097)
Timeframe: baseline to five years

Interventionmonths (Median)
Regimen A and B8.95

[back to top]

Overall Survival (Part I)

Length of subject survival after starting study treatment (NCT00240097)
Timeframe: baseline to 2 years

Interventionmonths (Median)
Regimen A and B12.9

[back to top]

Progression-free Survival

progression-free survival (NCT00247416)
Timeframe: Pre-treatment, pre-cycles 3 & 5,4 weeks after last treatment, and every 3 months, an average of 471 days

Interventiondays (Median)
Arm 1, Control, no Dexamethasone Pretreatment101
Arm 2, Dexamethasone Pretreatment Test Arm122

[back to top]

Effect of Dexamethasone Pre-treatment on Overall Survival.

Overall survival (NCT00247416)
Timeframe: Pre-treatment, pre-cycles 3 & 5,4 weeks after last treatment, every 3 months, an average of 471 days

Interventiondays (Median)
Arm 1, Control, no Dexamethasone Pretreatment291
Arm 2, Dexamethasone Pretreatment Test Arm378

[back to top]

Effect of Dexamethasone Pre-treatment on Response Rate.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00247416)
Timeframe: Pre-treatment, pre-cycles 3 & 5, and up to 4 weeks after last treatment

Interventionpercentage of responders out of total (Number)
1 No Dex8
2 Dex26

[back to top]

Percentage of Participants With Reduction in Grade 3/4 Neutropenia

Reduction grade 3/4 neutropenia (NCT00247416)
Timeframe: continuous throughout treatment, up to 25 weeks

Interventionpercentage of participants (Number)
Arm 1, Control, no Dexamethasone Pretreatment40
Arm 2, Dexamethasone Pretreatment Test Arm13

[back to top]

Objective Response Rates (ORR)

To determine the objective response rates (CR + PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. (NCT00248287)
Timeframe: 2 years

InterventionPercentage of Participants (Number)
Irinotecan+Carboplatin36.4
Irinotecan+Carboplatin+Cetuximab36.6

[back to top]

Median Overall Survival (OS)

OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. (NCT00248287)
Timeframe: 2 years

Interventionmonths (Median)
Irinotecan+Carboplatin12.5
Irinotecan+Carboplatin+Cetuximab14.6

[back to top]

Median Time of Progression-free Survival (PFS)

PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date. (NCT00248287)
Timeframe: 2 years

Interventionmonths (Median)
Irinotecan+Carboplatin4.4
Irinotecan+Carboplatin+Cetuximab4.6

[back to top]

Duration of Response

"The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented.~Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD." (NCT00248287)
Timeframe: From date of randomization until the date of first documented progression or the date of death from any cause, whichever came first, assessed up to 60 months.

Interventionmonths (Median)
Irinotecan+Carboplatin5.4
Irinotecan+Carboplatin+Cetuximab6.0

[back to top]

Engraftment DLT

"• Engraftment toxicity: delayed engraftment and/or failure to engraft defined as:~neutrophils (ANC) < 500/μL by day 28 post transplant, or~platelets < 20,000 /μL by day 56 post transplant, or~if additional stem cells are required to be infused for any medical reason prior to initial engraftment of neutrophils or platelets." (NCT00253435)
Timeframe: From treatment start until 60 days post stem cell infusion

Interventionparticipants (Number)
Poor Risk Patients2
Good Risk Patients1

[back to top]

Dose Limiting Veno-occlusive Disease (VOD) / Sinusoidal Obstruction Syndrome SOS

"Dose limiting veno-occlusive disease (VOD) defined as:~the presence of hepatomegaly with right upper quadrant tenderness and an elevation of total bilirubin > grade 1, PLUS~the presence of grade 3 abnormalities of any ONE of the following: total bilirubin, hypoalbuminemia, weight gain, or hypoxia without other attribution" (NCT00253435)
Timeframe: Between start of MIBG treatment and 60 days post stem cell infusion

Interventionparticipants (Number)
Poor Risk Patients6
Good Risk Patients0

[back to top]

Response (Complete Response, Very Good Partial Response, and Partial Response) at 60-days Post Stem Cell Infusion

Tumor response based on evaluation performed on day 60 or at the time of disease progression/recurrence or start of another treatment - whichever comes first. Such evaluations will include 123I-MIBG scan, CT/MRI, urine catecholamine measurement, and bone marrow analysis (for those with marrow disease at study entry). (NCT00253435)
Timeframe: Response assessed 60 days post stem cell infusion

Interventionparticipants (Number)
Poor Risk Patients4
Good Risk Patients3

[back to top]

Event-free Survival (EFS) at 3 Years

EFS will be measured from start of treatment until progression, death or start of another treatment - whichever comes first. We report the estimated probability of EFS at 3 years. (NCT00253435)
Timeframe: 3 years since start of treatment

InterventionEstimated probability (Number)
Poor Risk Patients0.20
Good Risk Patients0.38

[back to top]

Overall Clinical Response to the Dose Dense Regimen

Measure clinical response rates in patients with breast cancer more than 2 cm and/or lymph node positive breast cancer treated with 2- 4 cycles of biweekly doxorubicin, cyclophosphamide with GMCSF (day 4-13) followed by weekly carboplatin/nab-paclitaxel given for 3 weeks, followed by 1 week of rest, for a total of 9-12 doses. (Her-2 positive patients, in addition, will receive Trastuzumab weekly (12-16 doses) and Her-2 negative patients will receive Bevacizumab (6-8 doses) q 2 weeks). (NCT00254592)
Timeframe: 3 years

InterventionParticipants (Count of Participants)
Chemotherapy With GM-CSF43

[back to top]

Overall Objective Response

"Overall objective response to therapy Complete remission/unconfirmed (CRu)~This includes patients who meet criteria for CR with the following exceptions:~1. A residual lymph node mass > 1.5 cm in the short axis with normalization of 18Ffluorodeoxyglucose- PET scan Partial remission/minimal response (PR and MR)~Any decrease in lymph nodes and nodal-based masses~Any decrease in PET avidity (however, residual FDG uptake is present)~Involving organs involved prior to therapy must have diminished in size.~No new sites of disease Stable disease Response is less than that which constitutes a PR and disease does not meet criteria for progressive disease Progressive disease~1. Increase in lymph nodes or nodal-based masses, or other measurable disease from pretreatment observations. 2. Appearance of any new lesion at the end of therapy" (NCT00255723)
Timeframe: 3 years

,
Interventionparticipants (Number)
Complete RemissionPartial Remission (PR)Progression of Disease (POD)
Arm A4563
Arm B3117

[back to top]

Microscopic Pathological Response Rate

pathological response rate: No evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. (NCT00256243)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
Chemotherapy With GM-CSF47

[back to top]

Clinical Response Rate

Clinical response (CR): Normal breast on physical exam. No mass, no thickening, no erythema, no peau d'orange. (NCT00256243)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
Chemotherapy With GM-CSF47

[back to top]

Percent of Patients Estimated to be Progression-Free and Alive

This estimate was determined by using a statistical method of analysis (Kaplan-Meier). (NCT00258362)
Timeframe: 1 Year, 2 Years, 3 Years

InterventionPercentage of Patients (Number)
1 Year2 Years3 Years
Patients With Endometrial Cancer867668

[back to top]

Percent of Patients Estimated to be Alive

This estimate of overall survival was determined by using the statistical method (Kaplan-Meier) of analysis. (NCT00258362)
Timeframe: 1 Year, 2 Years, 3 Years

InterventionPercentage of Patients (Number)
1 Year2 Years3 Years
Patients With Endometrial Cancer949180

[back to top]

Impact on Quality of Life Measured by the Functional Assessment of Cancer Therapy-Ovary Trial Outcome Index (FACT-O TOI)

Estimated least squares means from a mixed module of Quality of Life (QOL) scores at each assessment point, adjusted for baseline score and patient's age. Note: The range of possible scores of the FACT-O TOI is 0 - 104 for all treatment groups and at all visits. A higher score indicates better QOL. Baseline mean scores are raw means. (NCT00262847)
Timeframe: At baseline, 9, 18, 36, 60, and 84 weeks

,,
Interventionunits on a scale (Least Squares Mean)
prior to treatmentprior to cycle 4prior to cycle 7prior to cycle 13prior to cycle 216 months followup
Arm I (Placebo, Paclitaxel, Carboplatin)68.273.876.080.677.675.8
Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)68.071.174.380.579.177.6
Arm III (Paclitaxel, Carboplatin, Bevacizumab)67.470.973.879.978.677.8

[back to top]

Frequency and Severity (Grade 3 or Above) of Adverse Events Assessed by Common Terminology Criteria for Adverse Events Version 3.0

Eligible and Evaluable patients (NCT00262847)
Timeframe: Up to 5 years

,,
InterventionParticipants (Count of Participants)
White blood cellAbsolute neutrophil countHemoglobinPlateletsOther hematologicAllergy/ImmunologyAuditory/EarhypertensionCardiacCoagulationConstitutionalDermatologicEndocrineGastrointestinalGenitourinary/RenalHemorrhageHepatobiliaryInfectionLymphaticsMetabolicMusculoskeletalNeurosensoryOther neurologicalOcular/VisualPainPulmonaryVascularDeath, not CTC codedSexual/Reproductive
Arm I Toxicities (Placebo, Paclitaxel, Carboplatin)317540919313231101456213496135275491162344474293751
Arm II Toxicities (Placabo,Paclitaxel,Carboplatin,Bevacizumab)3285438612213251361276120411289173387172642182363380
Arm III Toxicities (Paclitaxel, Carboplatin, Bevacizumab)3275367413191426518883162122815395310121286541013240100

[back to top]

Overall Survival

Median overall survival (OS) (NCT00262847)
Timeframe: From study entry to death or last contact, up to 6 years

Interventionmonths (Median)
Arm I (Placebo, Paclitaxel, Carboplatin)40.6
Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)38.7
Arm III (Paclitaxel, Carboplatin, Bevacizumab)43.8

[back to top]

Progression-free Survival

Median progression-free survival (PFS). Onset of progression could be based on radiographic (RECIST) criteria or rising CA-125 (GCIG criteria). (NCT00262847)
Timeframe: From study entry until first disease progression, death or date of last contact, up to 6 years

Interventionmonths (Median)
Arm I (Placebo, Paclitaxel, Carboplatin)11.0
Arm II (Placebo, Paclitaxel, Carboplatin, Bevacizumab)12.3
Arm III (Paclitaxel, Carboplatin, Bevacizumab)15.3

[back to top]

Progression Free Survival (PFS)

Interval between date of randomization and earliest date of objective disease progression per RECIST criteria or death due to any cause in the absence of progression (NCT00264498)
Timeframe: Date of randomization to earliest date of objective disease progression

InterventionDays (Mean)
Active Comparator131.0
Experimental42.0

[back to top]

Determine the Antitumor Activity of Gemcitabine/Carboplatin/Bevacizumab Regimen as Measured by the Probability of Surviving Progression-free for at Least 6 Months or Responding.

Progression-free survival (PFS) by RECIST, and safety. RECIST verison 1.0 was used for the assessment of progression and was based on radiologic evaluation. (NCT00267696)
Timeframe: up to 6 months

Interventionmonths (Median)
Gemcitabine/Carboplatin/Bevacizumab13.3

[back to top]

Overall Survival for Patients Treated With the Regimen.

The period of time from study entry until disease progression or date of last contact. (NCT00267696)
Timeframe: To progression of Disease

Interventionmonths (Median)
Gemcitabine/Carboplatin/Bevacizumab36.1

[back to top]

Overall Survival

Time from registration to death due to any cause. (NCT00268437)
Timeframe: From baseline to 4 years

Interventionmonths (Median)
Pemetrexed/Carboplatin17.8

[back to top]

Pathologic Complete Response Rate

The proportion of pathologic complete responses will be estimated by the number of pathologic complete responses divided by the total number of evaluable patients. Ninety-five percent confidence intervals for the true pathologic complete response rate will be calculated. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for Measurable disease is defined as at least one lesion whose longest diameter can be accurately measured as ≥2.0 cm with conventional techniques or as ≥1.0 cm with spiral CT. Lesions on chest x-ray are acceptable as measurable lesions when they are clearly defined and surrounded by aerated lung. However, CT is preferable. (NCT00268437)
Timeframe: Baseline to time of surgery (around 10 - 18 weeks post-baseline)

Interventionpercentage of participants (Number)
Pemetrexed/Carboplatin23

[back to top]

Percent of Subjects With Best Overall Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria.

Objective response measured by Response Evaluation Criteria In Solid Tumors (RECIST) criteria and is Complete Response (disappearance of all target lesions) plus Partial Response (at least 30% decrease in sum of longest diameter [LD] of target lesions compared baseline sum of LD). (NCT00268905)
Timeframe: From start of eribulin treatment until disease progression or death

,,
Interventionpercentage of subjects (Number)
Best Overall Response RateComplete ResponsePartial ResponseStable DiseaseProgressive DiseaseNot Evaluable
Eribulin Mesylate 1.1 mg/m^2 Plus Carboplatin AUC 627.3027.336.49.127.3
Eribulin Mesylate Dose Finding Plus Carboplatin AUC 572.34.748.832.611.6
Eribulin Mesylate Dose Finding Plus Carboplatin AUC 611.1011.133.322.233.3

[back to top]

Safety of Eribulin Mesylate in Combination With Carboplatin as Measured by the Number of Subjects With Treatment Emergent Adverse Events.

Adverse events were considered treatment emergent if they started on or after the date of administration of the first dose of study drug, or if they were present prior to the administration of the first dose of study drug and increased in severity during the study. (NCT00268905)
Timeframe: Throughout the entire study

Interventionparticipants (Number)
Eribulin Mesylate Dose Finding Plus Carboplatin AUC 542
Eribulin Mesylate Dose Finding Plus Carboplatin AUC 69
Eribulin Mesylate 1.1 mg/m^2 Plus Carboplatin AUC 612

[back to top]

Maximum Tolerated Dose (MTD) of Eribulin Mesylate of E7389 in Combination With Carboplatin in Subjects With Advanced Solid Tumors.

MTD was established by summarizing the number and percent of subject with dose- limiting toxicities (DLTs) for the first cycle. (NCT00268905)
Timeframe: 21 days (first cycle)

Interventionmg/m^2 (Number)
Eribulin Mesylate Dose Finding Plus Carboplatin AUC 51.4
Eribulin Mesylate Dose Finding Plus Carboplatin AUC 61.1
Eribulin Mesylate 1.1 mg/m^2 Plus Carboplatin AUC 61.1

[back to top]

Overall Survival at 6 Years

For each treatment arm, the Kaplan-Meier technique was used to estimate the 6 year survival rate. Results are presented as probability (%) of survival at 6 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date. (NCT00269152)
Timeframe: Baseline to date of death from any cause assessed at 6 years

Interventionpercent probability of survival (%) (Number)
Pemetrexed + Cisplatin72.6
Pemetrexed + Carboplatin83.2

[back to top]

Grade III/IV Adverse Events

Number of participants experiencing Grade III/IV hematologic and non-hematologic adverse events possibly related to study drug or protocol procedures in this study. (NCT00269152)
Timeframe: every 21-day cycle for 4 cycles

,
Interventionparticipants (Number)
NeutropeniaAnaemiaThrombocytopeniaFebrile neutropeniaLeukopeniaLymphopeniaNeutrophil count decreasedHaemoglobin count decreasedPlatelet count decreasedWhite blood cell count decreasedAstheniaNauseaVomitingFatigueCatheter related infectionGamma-glutamyltransferase increasedAnorexiaHyperglycaemiaHyperkalaemiaPsychotic disorder
Pemetrexed + Carboplatin63321062122002000000
Pemetrexed + Cisplatin90000110104330111111

[back to top]

The Feasibility of Post-Surgery Chemotherapy

Feasibility was measured by completion of 4 treatment cycles without remaining toxicities >=Grade 3 at 30 days after last infusion. (NCT00269152)
Timeframe: every 21-day cycle for 4 cycles up to 30 days after last infusion

,
Interventionparticipants (Number)
"Participants feasible"Non-feasible = Early DiscontinuationNon-feasible = Lost to Follow-upNon-feasible = Remaining Grade 3/4 ToxicityNon-feasible = Underdosage (<95% intended dose)
Pemetrexed + Carboplatin2762319
Pemetrexed + Cisplatin3818145

[back to top]

3 Year Disease-Free Survival: Probability of Disease-Free Survival at 3 Years

For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year disease-free rate. Disease-free survival is defined as the time from enrollment to the first observation of disease progression, or death due to any cause. For participants not known to have died and to have had recurrent disease, disease-free survival was censored at the date of the last participant contact with No Recurrence status. Results are presented as probability (%) of disease-free survival at 3 years. (NCT00269152)
Timeframe: length of time disease free, assessed at 3 years

Interventionprobability of disease-free survival (%) (Number)
Pemetrexed + Cisplatin61.2
Pemetrexed + Carboplatin67.3

[back to top]

Overall Survival at 3 Years

For each treatment arm, the Kaplan-Meier technique was used to estimate the 3 year survival rate. Results are presented as probability (%) of survival at 3 years. Overall survival is the duration from enrollment to death. For participants not known to have died, overall survival was censored at the last known alive date. (NCT00269152)
Timeframe: baseline to date of death from any cause, assessed at 3 years

Interventionpercent probability of survival (%) (Number)
Pemetrexed + Cisplatin82.0
Pemetrexed + Carboplatin83.2

[back to top]

Participants With Mucositis and Hematological Toxicities With the Addition of Radioprotector Amifostine

Blood work (CMP was collected and evaluated for neutropenia, leukopenia and anemia) is taken prior to chemotherapy administration. The toxicity levels were measured using Common Terminology Criteria for Adverse Events (CTCAE 3.0) and monitored based on the dose of Amifostine given. (NCT00270790)
Timeframe: 3 years

Interventionparticipants (Number)
AMIFOSTINE +CARBOPLATIN, TAXOL +RT16

[back to top]

Response Rates Based on the Study Regimen

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00270790)
Timeframe: 3 years

Interventionparticipants (Number)
AMIFOSTINE +CARBOPLATIN, TAXOL +RT16

[back to top]

Time to Progression-Free Survival (PFS)

Bevacizumab has recently been demonstrated to prolong overall survival when added to carboplatin and paclitaxel for chemotherapy-naı¨ve patients with nonsquamous nonsmall-cell lung cancer (NSCLC). However, the effects of combining bevacizumab with other standards, front-line, platinum-based doublets have not been extensively explored.We designed this single treatment arm, phase 2 trial to determine whether the combination of carboplatin, docetaxel, and bevacizumab is tolerable and prolongs progression-free survival of chemotherapy-naı¨ve patients with advanced, on squamous NSCLC. (NCT00271505)
Timeframe: Baseline up to 12 months or disease progression/death

Interventionmonths (Median)
Carboplatin, Docetaxel, and Bevacizumab7.9

[back to top]

Disease Control Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1 .0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR)= CR+ PR. (NCT00271505)
Timeframe: Baseline start of treatment to death, assessed up to 6 years

Interventionpercentage of participants (Mean)
Carboplatin,Docetaxel, and Bevacizumab95

[back to top]

Overall Survival (OS)- 5 Years

Secondary endpoints of the study included the assessment of overall survival, disease control rate (CR þPR þ SD, defined by RECIST16), and evaluation of the safety profile of this triple-agent regimen. All patients who received at least 1 dose of the study drug were analyzed for efficacy and toxicity endpoints. (NCT00271505)
Timeframe: Baseline start of treatment to death, assessed up to 6 years

Interventionmonths (Median)
Carboplatin,Docetaxel, and Bevacizumab16.5

[back to top]

5-year Overall Survival

5-year overall survival is defined as the probability of patients who remain alive at 5 years from study entry. The method of Kaplan and Meier (1958) was used to estimate overall survival. (NCT00274924)
Timeframe: Every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.

Interventionprobability (Number)
Group I (PET Negative)0.77
Group II (PET Positive)0.69

[back to top]

2-year Progression-Free Survival (PFS)

2-year progression-free survival is defined as the probability of patients who remain alive and progression free at 2 years from study entry. The method of Kaplan and Meier (1958) was used to estimate PFS. (NCT00274924)
Timeframe: Assessed every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.

Interventionprobability (Number)
Group I (PET Negative)0.76
Group II (PET Positive)0.42

[back to top]

Overall Survival

Percent of participants still alive from the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up. (NCT00278148)
Timeframe: 3 years

Interventionpercentage of participants (Number)
Erlotinib, Paclitaxel, and Carboplatin With Radiation69

[back to top]

Progression Free Survival (PFS)

Months from the date of study entry to the date of the corresponding event (recurrence of death) or the date of final follow-up (NCT00278148)
Timeframe: 3 years

Interventionmonths (Median)
Erlotinib, Paclitaxel, and Carboplatin With Radiation41.8

[back to top]

Pathological Complete Response Rate

"Number of participants with an pathological complete response rate using the RECIST criteria.~Complete response: Disappearance of all measurable and evaluable disease Partial response: A 30% or greater decline in the sum of the longest diameter of target lesions compared to the baseline measurement.~Progressive disease: A 20% or greater increase in the sum of the longest diameter of the target lesions compared to the baseline.~Stable disease: Disease that did not meet the criteria for a CR / PR or progressive disease." (NCT00278148)
Timeframe: 2 years

Interventionparticipants (Number)
Erlotinib, Paclitaxel, and Carboplatin With Radiation6

[back to top]

Maximum Tolerated Dose of Erlotinib Hydrochloride (Phase I)

The Phase I portion of this study is to determine the Maximum Tolerated Dose (MTD) of combining OSI-774 with the paclitaxel-carboplatin chemoradiation protocol and to assess the safety and feasiblity of this combination. (NCT00278148)
Timeframe: 2 weeks after surgery

Interventionmg daily (Number)
Erlotinib, Paclitaxel, and Carboplatin With Radiation150

[back to top]

Response Rate to Induction Therapy (Phase I [Closed to Accrual as of 1/3/2008] and II)

"Measurable lesions must be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10mm with spiral CT scan or nonmeasurable, but evaluable. Evaluable is nonmeasurable disease that includes ascites, malignant pleural/pericardial effusion, bone lesions, or marrow involvement. The same method of assessment and the same techniques should be used to characterize each identified and reported lesion at baseline and during follow-up.~Complete Response (CR)- Disappearance of all target lesions" (NCT00280150)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
Overall Study0

[back to top]

Overall Response Rate and Survival Profile

The overall response rate (ORR) to the two cycles of induction therapy plus bevacizumab in stage IIIA/B NSCLC. ORR is the portion of patients with a tumor size reduction for a minimum time period. Response duration is measured from the time of initial response until documented tumor progression. (NCT00280150)
Timeframe: 5 years

Interventionpercentage of participants (Number)
Overall Study39

[back to top]

Progression-free Survival (PFS)

The length of time during and after the treatment of a stage IIIA/B NSCLC that a patient lives with the disease but it does not get worse. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00280150)
Timeframe: 5 years

InterventionMonths (Median)
Overall Study10.2

[back to top]

Safety and Toxicity Profile of Combining Both Bevacizumab and Erlotinib Hydrochloride With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy

A list of Hematologic and nonhematologic toxicities associated with induction and concurrent therapy. This includes the percentage of patients who experienced grades 2-4 based on the National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0). (NCT00280150)
Timeframe: 6 weeks after completion of therapy

,
Interventionpercentage of participants (Number)
AnemiaNeutropheniaThrombocytopeniaFebrile neutropeniaNausea/vomitingFatigueAlopeciaHypertensionMyalgias/arthralgiasDiarrheaNeuropathyRashAnorexiaEsophagitisDehydrationHemorrhageHypomagnesemiaProteinuriaWeight lossPneumonitisHypersensitivity reaction
Concurrent Therapy1735162622940221164011642922
Induction Therapy4520072042927622000000004

[back to top]

Maximum Dose of Erlotinib When Given Together With Carboplatin, Paclitaxel, and Thoracic Conformal Radiotherapy (Phase I [Closed to Accrual as of 1/3/2008])

Dose-limiting toxicities (DLTs) were used to establish which cohort would be used for the phase II portion of the trial. DLTs were defined as any grade 3 or 4 nonhematologic toxicity with the exception of esophagitis, which had to be grade 4; grade 4 neutropenia lasting greater than or equal to 7 days and thrombocytopenia to less than 20,000/microliter. (NCT00280150)
Timeframe: 6 weeks after completion of therapy

InterventionDLTs (Number)
Cohort 10
Cohort 20
Cohort 32

[back to top]

Feasibility and Tolerability of Administering Consolidation Therapy

The proportion of patients who were able to complete consolidation therapy after induction therapy and chemoradiotherapy (NCT00280150)
Timeframe: 6 cycles

InterventionParticipants (Count of Participants)
Overall Study5

[back to top]

Number of Participants Who Completed Four Cycles of the Carboplatin/Docetaxel Regimen

Feasibility was based on the percentage of patients completing four cycles of the carboplatin/docetaxel regimen to a high fraction of patients with curatively resected stage IIIIA non-small cell lung cancer within 12 weeks. (NCT00280735)
Timeframe: 12 weeks from initiating adjuvant therapy

InterventionParticipants (Count of Participants)
Single Arm Trial57

[back to top]

Progression Free Survival

Relapse-free survival rate at 18 months. Patients were determined to have progression either by radiographic and/or pathological assessment by local physician per local standard of care monitoring for disease recurrence. (NCT00280735)
Timeframe: The time between the start of treatment to disease progression or death or the date of last contact, measured up to 18 months

Interventionpercentage of participants (Number)
Single Arm Trial86

[back to top]

Toxicity in Patients Treated With This Regimen

Safety determinations are based on the rate of drug-related adverse events (AEs) reported based upon the toxicity as measured by the NCI Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). (NCT00280735)
Timeframe: Day 1 of treatment to 30 days after treatment discontinuation

,,
Interventionpercentage of participants (Number)
NeutropeniaThrombocytopeniaFebrile NeutorpeniaNauseaVomitingDiarrheaInfusional reactionsDehydrationFatigue/astheniaSyncopeArrythmiaProteinuriaInfectionDyspnea
Grade 3 %2413113415.55.50000
Grade 3/4 %65111113415.55.51131
Grade 4 %420800000001131

[back to top]

Overall Survival

Overall survival rate at 18 months. (NCT00280735)
Timeframe: The time between the start of treatment to disease progression or death or the date of last contact, measured up to 18 months

Interventionpercentage of participants (Number)
Single Arm Trial86

[back to top]

Number of Patients Alive at 1 Year (Survival)

Participants who were alive at one year from date of enrollment . (NCT00281827)
Timeframe: 12 Months

InterventionParticipants (Number)
Intent-to-Treat21

[back to top]

Number of Patients Alive at 2 Years (Survival)

Participants who were alive at 2 years from date of enrollment. (NCT00281827)
Timeframe: 24 Months

InterventionParticipants (Number)
Intent-to-Treat16

[back to top]

Number of Patients Disease-free at 1 Year

Calculated from date of enrollment to date of recurrence or death, whichever came first (NCT00281827)
Timeframe: 1 year

InterventionParticipants (Number)
Intent-to-Treat14

[back to top]

Number of Patients Disease-free at 2 Years

Calculated from date of enrollment to date of recurrence or death, whichever came first (NCT00281827)
Timeframe: 2 Years

InterventionParticipants (Number)
Intent-To-Treat8

[back to top]

Number of Patients Reporting Clinical Response

Objective clinical response measuring using tumor assessments: Complete Response (CR) = disappearance of all target and non-target lesions and normalization of tumor marker level, if applicable. Pathological Complete Response (PCR) = No viable tumor cells in specimen determined by light microscopy. Partial Response (PR) = at least 30% decrease in the sum of longest diameter of target lesions from baseline. Progressive Disease (PD) = at least 20% increase in the sum of longest diameters of target lesions from baseline or new lesions. Stable Disease (SD) = Neither PR or PD. (NCT00281827)
Timeframe: At end of 3 -21 day cycles of treatment

InterventionParticipants (Number)
Complete ResponsePathological Complete ResponsePartial ResponseStable DiseaseProgressive Disease
Evaluable Patients001442

[back to top]

Number of Patients Alive at 56 Months (End of Study)

Patients alive from date of enrollment to date of death or censored at date of last contact (Overall Survival). (NCT00281827)
Timeframe: Up to 56 months

InterventionParticipants (Number)
Intent-to-Treat8

[back to top]

Overall Response Rate

Percentage of patients who experienced complete or partial response as defined by RECIST (NCT00287989)
Timeframe: after 6 cycles of chemotherapy

Interventionpercentage of participants (Number)
150 PRE18
1,500 PRE34
1,500 POST28

[back to top]

Time to Progression

Median number of months until disease progression (NCT00287989)
Timeframe: after cycle 6 of chemotherapy

Interventionmonths (Median)
150 PRE4
1,500 PRE4
1,500 POST5

[back to top]

Number of Participants With Response Following Treatment With 300 mg ZD6474 Daily (Study Part One)

Evaluate the response rate in patients receiving monotherapy with ZD6474 compared to ZD6474 plus carboplatin plus paclitaxel. No formal comparisons could be made and no conclusions drawn because of small numbers in the treatment groups; a result of an inability to fulfil the recruitment target. (NCT00290537)
Timeframe: Radiologic evaluations performed after weeks 2 and 9 of treatment, then every 2 cycles or as indicated if progressive disease is suspected up to 6 cycles or 18 weeks (1 cycle = 3 weeks).

InterventionParticipants (Number)
Complete ResponseNo Change/Stable DiseaseProgressive DiseaseInevaluable for Response
ZD64741111

[back to top]

Overall Survival at 12 Months

Percentage of patients alive after 12 months of study treatment (NCT00294762)
Timeframe: 12 months from 1st dose

InterventionPercent of Patients (Number)
Erlotinib58.6
Erlotinib + Chemotherapy (Intercalated)46.4

[back to top]

Overall Survival

Median number of months from first study treatment until time of death (NCT00294762)
Timeframe: From first study treatment until time of death (maximum 29.0 months)

InterventionMonths (Median)
Erlotinib16.72
Erlotinib + Chemotherapy (Intercalated)11.43

[back to top]

Duration of Tumor Response

Median length of time that tumor showed any type of response, ie, CR, PR, or SD (NCT00294762)
Timeframe: While receiving study treatment; assessed every 21 days until progression (maximum 28.8 months).

InterventionMonths (Median)
Erlotinib6.4
Erlotinib + Chemotherapy (Intercalated)4.1

[back to top]

6-month Progression-free Survival

Percentage of patients who's disease had not progressed at 6 months. Disease progression defined as radiological and/or symptomatic disease progression or death in absence of progression. (NCT00294762)
Timeframe: 6 months after first dose

InterventionPercentage of Patients (Number)
Erlotinib30.7
Erlotinib + Chemotherapy (Intercalated)26.4

[back to top]

Best Tumor Response

Change in size of tumor: Complete Response (CR) = no measurable tumor; Partial Response (PR) = 30% decrease in size of measurable tumor; Stable Disease (SD) = measurable tumor size has not changed; Progressive Disease (PD) = measurable tumor larger than at baseline (NCT00294762)
Timeframe: While receiving study treatment; assessed every 21 days until progression (maximum 28.8 months)

,
InterventionPercent of Patients (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Unable to Determine/Not Evaluable
Erlotinib011.634.846.47.2
Erlotinib + Chemotherapy (Intercalated)022.449.317.910.4

[back to top]

Progression-free Survival

Median time until disease progression. Disease progression defined as radiological and/or symptomatic disease progression or death in absence of progression. (NCT00294762)
Timeframe: Until time of disease progression, as assessed every 21 days (maximum 28.8 months)

Interventionmonths (Median)
Erlotinib2.69
Erlotinib + Chemotherapy (Intercalated)4.57

[back to top]

Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1.

"RCB score is determined using information on the size of the tumor and the extent of tumor cells in the breast and axillary lymph nodes after neoadjuvant therapy. The higher the RCB score, the more residual breast cancer there is in the breast and lymph nodes:~RCB-0 = No residual breast cancer RCB-I = Small amount of residual breast cancer RCB-II = Moderate amount of residual breast cancer RCB-III = Extensive (a lot of) residual breast cancer" (NCT00295893)
Timeframe: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months.

InterventionParticipants (Count of Participants)
Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide11
Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin10
Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab28

[back to top]

Count of Patients With Pathologic Complete Response (pCR)

pCR was defined as no evidence of residual invasive cancer (or very few scattered tumor cells) in primary tumor and lymph nodes. (NCT00295893)
Timeframe: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months

InterventionParticipants (Count of Participants)
Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide6
Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin4
Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab22

[back to top]

Duration of Response

Duration of response (PR or better) is defined as the time from the first documented objective response of PR or CR, whichever is noted earlier, to disease progression or death (if death occurs before progression is documented). (NCT00300885)
Timeframe: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis

Interventiondays (Median)
Sorafenib + C/P168
Placebo + C/P134

[back to top]

Progression Free Survival (PFS)

PFS determined as time (days) from the date of randomization at start of study to disease progression (radiological or clinical) or death due to any cause, if death occurs before progression. (NCT00300885)
Timeframe: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis

Interventiondays (Median)
Sorafenib + C/P139
Placebo + C/P163

[back to top]

Patient Reported Outcome as Assessed by FACT-L Score. Change From Baseline in Total FACT-L at Cycles 3,5,7,9 and End of Treatment (EOT)

"Functional Assessment of Cancer Therapy - Lung cancer subscore (FACT-L). Patient reported outcome as assessed by FACT-L score. FACT-L questionnaire comprises statements about physical, social / family, emotional and functional well-being as well as additional concerns which have to be rated by the patients (0=not at all to 4=very much). Cycle duration defined as 21 days. Change from baseline in Total FACT-L on day 1 of cycles 3,5,7,9 (weeks 7,13,19 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation." (NCT00300885)
Timeframe: Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every other cycle (i.e. Cycle 3, 5, 7 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis

,
InterventionScores on a scale (Mean)
Cycle 3, Day 1Cycle 5, Day 1Cycle 7, Day 1Cycle 9, Day 1End of treatment (EOT)
Placebo + C/P0.1-1.3-0.5-0.6-2.7
Sorafenib + C/P0.0-1.4-0.8-1.2-3.1

[back to top]

Overall Survival (OS) in Patients Treated With Carboplatin, Paclitaxel and Sorafenib to OS in Patients Treated With Carboplatin, Paclitaxel and Placebo

Overall survival determined as the time (days) from the date of randomization at start of study to the date of death, due to any cause. Outcome measure was assessed regularly, i.e. every 3 weeks during study treatment and every 3 months during post-treatment. (NCT00300885)
Timeframe: Outcome measure was assessed every 3 weeks starting from randomization, during treatment period and every 3 months during follow-up period until death was recorded or up to data cutoff (1Oct2007) used for planned formal interim analysis

Interventiondays (Median)
Sorafenib + C/P324
Placebo + C/P322

[back to top]

Overall Best Response

Best overall tumor response for the ITT population was determined according to Response Evaluation Criteria in Solid Tumors (RECIST). Categories: complete response (CR, tumor disappears), partial response (PR, sum of lesion sizes decreased), stable disease (SD, steady state of disease), progressive disease (PD, sum of lesion sizes increased). (NCT00300885)
Timeframe: Tumor measurements and assessments based on RECIST criteria were performed every 6 weeks for the first 18 weeks of therapy ( week 6, 12, and 18) and every 12 weeks thereafter up to data cutoff (1Oct2007) used for planned formal interim analysis

,
Interventionpercentage of participants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Not evaluatedDisease control
Placebo + C/P1.122.947.817.510.656.3
Sorafenib + C/P0.027.445.99.916.849.8

[back to top]

Patient Reported Outcome as Assessed by LCS Subscale Score. Change From Baseline in LCS Subscale at Cycles 2 Through 9 and at End of Treatment (EOT)

Lung Cancer Symptoms (LCS) subscale ranges from 0 (severe debilitation) to 28 (asymptomatic). Cycle duration defined as 21 days. Change from baseline in LCS Subscale on day 1 of cycles 2 through 9 (weeks 4,7,10,13,16,19,22 and 25) and end of treatment (EOT); cycle 1, day 1 used as baseline. EOT is determined by patient's last visit after treatment discontinuation. (NCT00300885)
Timeframe: Outcome measure was assessed on Day 1 of Cycle 1 and Day 1 of every cycle (i.e. Cycle 2, 3, 4, 5 etc.) during treatment and at end of treatment visit or up to data cutoff (10ct2007) used for planned formal interim analysis

,
InterventionScores on a scale (Mean)
Cycle 2, Day 1Cycle 3, Day 1Cycle 4, Day 1Cycle 5, Day 1Cycle 6, Day 1Cycle 7, Day 1Cycle 8, Day 1Cycle 9, Day 1End of treatment (EOT)
Placebo + C/P-0.1-0.2-0.3-0.5-0.4-0.4-0.2-0.3-0.4
Sorafenib + C/P0.0-0.4-0.6-0.6-0.8-0.8-1.2-0.9-0.9

[back to top]

Number of Participants With Complete Response

Number of participants with a complete response. Complete Response (CR): Disappearance of clinical and radiological evidence of tumor. (NCT00301028)
Timeframe: Study period of 3 Years

Interventionparticipants (Number)
Cetuximab + Carboplatin/Paclitaxel39

[back to top]

Objective Response Rate (ORR)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective response (OR) = CR + PR. (NCT00303108)
Timeframe: From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.

Interventionpercentage of participants (Number)
D+C and Taxane Naive30.8
D+C and Taxane Pretreated31.0
D+C+H55.6

[back to top]

Progression-free Survival (PFS)

"PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.~Progression is defined as appearance of one or more new lesions. Unequivocal progression of existing non-target lesions. Although a clear progression of non-target lesions only is exceptional, in such circumstances, the opinion of the Treating Physician should prevail, and the progression status should be confirmed at a later time by the review panel." (NCT00303108)
Timeframe: 30 months

Interventionmonths (Median)
D+C and Taxane Naive8.1
D+C and Taxane Pretreated5.4
D+C+H10.1

[back to top]

Duration of Response

Duration from date of stating treatment to the date of first CR or PR. (NCT00303108)
Timeframe: From date of randomization until the date of first documented progression or date of intolerable toxicity, whichever came first, assessed up to 54 months.

Interventionmonths (Median)
D+C and Taxane Naive11.1
D+C and Taxane Pretreated7.0
D+C+H11.8

[back to top]

1-year Overall Survival

OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. (NCT00303108)
Timeframe: 1 year

Interventionprobability of overall survival (Number)
D+C and Taxane Naive0.83
D+C and Taxane Pretreated0.56
D+C+H0.90

[back to top]

Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment

"Overall response rate is the percent of patients experiencing a complete or partial response by RECIST v. 1 Criteria. Overall response rate is the percentage of patients with complete response or partial response per RECIST v.1 Criteria. Complete response (CR) = Disappearance of all target lesions, disappearance of all nontarget lesions for at least 4 weeks. Partial Response (PR) = At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters.~The final response category assigned represented the best response obtained during treatment." (NCT00305942)
Timeframe: 18 months

Interventionpercentage of participants (Number)
Topotecan/Carboplatin57

[back to top]

Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease

Time to progression is defined as the interval between the start date of treatment and the date of occurrence of progressive disease. (NCT00305942)
Timeframe: 18 months

InterventionMonths (Median)
Topotecan/Carboplatin5.5

[back to top]

Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

Overall survival was measured from the date of study entry until the date of death. (NCT00305942)
Timeframe: 18 months

InterventionMonths (Median)
Topotecan/Carboplatin8.5

[back to top]

Time to Disease Progression

Time to disease progression was defined as the time from randomization to the first date of documented disease progression or death if the participant dies due to disease progression. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.0) criteria. Progressive disease (PD) was defined as having at least a 20% increase in sum of the longest diameter of target lesions. For participants who have not had documented disease progression, time to disease progression was censored at the date of death or date of last visit. For participants who received other anti-tumor therapy prior to disease progression, time to disease progression was censored at the first available date of other anti-tumor therapy. (NCT00308750)
Timeframe: Baseline to measured PD up to 22.3 months

Interventionmonths (Median)
Enzastaurin/Pemetrexed/Carboplatin4.6
Pemetrexed/Carboplatin6.0
Docetaxel/Carboplatin4.1

[back to top]

Time-to-Treatment Failure (TTF)

TTF was defined as the time from randomization to the first observation of PD, death due to any cause, or early discontinuation of treatment. Response was defined using RECIST, version 1.0 criteria. PD was defined as having at least a 20% increase in sum of longest diameter of target lesions. TTF was censored at the date of the last follow-up visit for participants who did not discontinue early, who were still alive, and who have not progressed. (NCT00308750)
Timeframe: Baseline to stopping treatment up to 14.1 months

Interventionmonths (Median)
Enzastaurin/Pemetrexed/Carboplatin2.6
Pemetrexed/Carboplatin3.8
Docetaxel/Carboplatin2.6

[back to top]

Change From Baseline in Total Functional Assessment of Cancer Therapy -Taxane (FACT-Taxane) Scale

"The FACT-Taxane version 4 scale is used to assess HRQoL in participants receiving taxane chemotherapy. The FACT-taxane has 5 subscales: PWB, SFWB, and FWB subscales which include 7 items each, EWB subscale which includes 6 items, and a taxane subscale which include 16 items and has two domains (neurotoxicity and taxane). Total FACT-Taxane is the sum of all the 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 worst quality of life to 172 best quality of life. The LS mean was calculated using an ANCOVA model adjusted for change scores and baseline scores." (NCT00308750)
Timeframe: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each]

,,
Interventionunits on a scale (Least Squares Mean)
Cycle 1 (Week 3)Cycle 2 (Week 6)Cycle 3 (Week 9)Cycle 4 (Week 12)Cycle 5 (Week 15)Cycle 6 (Week 18)
Docetaxel/Carboplatin-2.17-3.13-4.40-2.58-7.74-0.34
Enzastaurin/Pemetrexed/Carboplatin-3.16-6.22-1.89-2.28-2.522.77
Pemetrexed/Carboplatin-0.78-5.66-1.52-0.77-3.11-2.81

[back to top]

Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale

"The FACT-L version 4 scale is used to assess health-related quality of life (HRQoL) in participants with lung cancer. The FACT-L has 5 subscales: Physical Well-Being (PWB), Social and Family Well-Being (SFWB) and Functional Well-Being (FWB) subscales which include 7 items each, Emotional Well-Being (EWB) subscale which includes 6 items, and a Lung-Cancer Specific (LCS) subscale which include 7 items. Total FACT-L is the sum of all 5 subscales. Each item is scored from 0 to 4 giving a total overall score from 0 equal to worst quality of life to 136 equal to best quality of life. The Least Square (LS) mean was calculated using an analysis of covariance (ANCOVA) model adjusted for change scores and baseline scores." (NCT00308750)
Timeframe: Baseline, Cycle 1 (Week 3), Cycle 2 (Week 6), Cycle 3 (Week 9), Cycle 4 (Week 12), Cycle 5 (Week 15) and Cycle 6 (Week 18) [21-day cycle each]

,,
Interventionunits on a scale (Least Squares Mean)
Cycle 1 (Week 3)Cycle 2 (Week 6)Cycle 3 (Week 9)Cycle 4 (Week 12)Cycle 5 (Week 15)Cycle 6 (Week 18)
Docetaxel/Carboplatin-3.33-2.16-1.93-0.81-4.693.38
Enzastaurin/Pemetrexed/Carboplatin-3.98-3.250.390.311.897.38
Pemetrexed/Carboplatin1.12-1.540.643.54-0.26-0.83

[back to top]

Duration of CR or PR (Duration of Response)

The duration of a CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death due to any cause. Response was defined using RECIST, version 1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. (NCT00308750)
Timeframe: Date of first response to the date of progression or death due to any cause up to 22.3 months

Interventionmonths (Median)
Enzastaurin/Pemetrexed/Carboplatin7.4
Pemetrexed/Carboplatin9.3
Docetaxel/Carboplatin5.8

[back to top]

Number of Participants With Adverse Events (AEs) or Deaths

Data presented are the number of participants who experienced 1 or more AEs or any serious AEs (SAEs) regardless of causality, or deaths during the study including 30 days after treatment discontinuation. A summary of SAEs and other non-serious AEs is located in the Reported Adverse Events section of this report. (NCT00308750)
Timeframe: Baseline through study completion up to 6 cycles (21-day cycle each) and 30-day safety follow-up

,,
InterventionParticipants (Count of Participants)
AEsSAEsDeaths Due to AEs
Docetaxel/Carboplatin69264
Enzastaurin/Pemetrexed/Carboplatin63353
Pemetrexed/Carboplatin70205

[back to top]

Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response]

Response was defined using RECIST, version 1.0 criteria. Participants with a best response of CR or PR were considered to have had a tumor response. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. (NCT00308750)
Timeframe: Baseline to measured PD up to 22.3 months

InterventionParticipants (Count of Participants)
Enzastaurin/Pemetrexed/Carboplatin9
Pemetrexed/Carboplatin16
Docetaxel/Carboplatin19

[back to top]

Overall Survival (OS)

OS was the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact. (NCT00308750)
Timeframe: Baseline to date of death from any cause up to 35 months

Interventionmonths (Median)
Enzastaurin/Pemetrexed/Carboplatin7.2
Pemetrexed/Carboplatin12.7
Docetaxel/Carboplatin9.2

[back to top]

The Number of Participants Classified as Responders in Cancer Antigen 125 (CA-125)

"CA-125 is a tumor marker, found in greater concentration in tumor cells than other cells of the body. Participants were classed as responders if their CA-125 level at the end of study was 50% or less of baseline. In addition, a confirmatory sample (taken at least 28 days after the first sample) must have also been 50% or less of baseline." (NCT00316173)
Timeframe: Baseline to end of study (up to 54.7 weeks).

Interventionparticipants (Number)
Activity Assessment Phase23

[back to top]

Duration of Response

"Duration of response was calculated as the time from first documented PR or CR until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was censored." (NCT00316173)
Timeframe: From time of PR or CR to disease progression/death (up to 56.0 weeks)

Interventionweeks (Median)
Activity Assessment Phase42.64

[back to top]

Progression-free Survival

"Progression-free survival (PFS) was calculated as the time from the start of treatment until disease progression or death. For participants who did not have disease progression or did not die, the date on which alternative anti-cancer therapy began was used, or the date of last contact (if sooner). The word used for such participants was censored. Although Time to Disease Progression was stated as an endpoint in the protocol, the definition given in the protocol (and used in the study) was that of PFS. As such, PFS was measured, not Time to Disease Progression." (NCT00316173)
Timeframe: From start of treatment to disease progression/death (up to 67.7 weeks)

Interventionweeks (Median)
Activity Assessment Phase44.29

[back to top]

Number of Participants Who Died From the Start of Treatment to Follow-up

"The number of participants who died from the start of treatment to follow-up was calculated. For participants who did not die, the date of last contact was used. The word used for such participants was censored." (NCT00316173)
Timeframe: From start of treatment to death (up to 110.4 weeks).

Interventionparticipants (Number)
DiedCensored
Activity Assessment Phase847

[back to top]

Time to Response

Time to response was calculated as the time from start of treatment until first evidence of partial response (PR; >50% decrease in the measurements of the largest lesions with no appearance of new lesions) or complete response (CR; complete disappearance of all lesions). (NCT00316173)
Timeframe: From start of treatment to evidence of PR or CR (up to 39.3 weeks)

Interventionweeks (Median)
Activity Assessment Phase6.57

[back to top]

Number of Participants With the Indicated Response

Overall response rate, as determined by radiologic evaluation (utilizing the World Health Organization [WHO] criteria and/or physical examination was measured. Complete response (CR: complete disappearance of all lesions), partial response (PR: >50% decrease in the measurements of the largest lesions with no appearance of new lesions), stable disease (SD: no change in tumor size for at least 8 weeks) and progressive disease (PD: >25% increase in measurements of lesions or appearance of new lesions). (NCT00316173)
Timeframe: From start of treatment to evidence of CR or PR (up to 39.3 weeks).

Interventionparticipants (Number)
Complete responsePartial responseStable diseaseProgressive diseaseNot evaluable
Activity Assessment Phase61120711

[back to top]

Grade 3 (Severe) Hematological Toxicities

Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade. (NCT00316186)
Timeframe: Week 1 through Endpoint (variable based on disease progression or toxicity

Interventionparticipants (Number)
AnemiaNeutropeniaThrombocytopeniaLeukopenia
Intravenous Topotecan and Carboplatin4424

[back to top]

Grade 1 (Mild) Hematological Toxicities

Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade. (NCT00316186)
Timeframe: Week 1 through Endpoint (variable based on disease progression or toxicity)

Interventionparticipants (Number)
AnemiaNeutropeniaThrombocytopeniaLeukopenia
Intravenous Topotecan and Carboplatin1211513

[back to top]

Grade 4 (Life-threatening or Disabling) Hematological Toxicities

Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade. (NCT00316186)
Timeframe: Week 1 through Endpoint (variable based on disease progression or toxicity

Interventionparticipants (Number)
AnemiaNeutropeniaThrombocytopeniaLeukopenia
Intravenous Topotecan and Carboplatin2420

[back to top]

Overall Response Rate, as Determined by Radiologic Evaluation (Utilizing the World Health Organization [WHO] Criteria), Calculated as the Number of Participants With the Indicated Response

The categories of tumor response were: complete response (complete disappearance of all known lesions determined by 2 measurements not less than 4 weeks apart), partial response (>50% decrease in measurable lesions for at least 4 weeks with no appearance of new lesions), stable disease (no change in tumor size for at least 8 weeks), progressive disease (>25% increase in measurements of lesions or appearance of new lesions), and not evaluable. The overall response rate was determined using a scan performed within the first 30 days of the first response. (NCT00316186)
Timeframe: Baseline until up to Day 169

InterventionParticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseNot Evaluable
Intravenous Topotecan and Carboplatin081168

[back to top]

Grade 2 (Moderate) Hematological Toxicities

Hematology evaluation included hemoglobin, hematocrit, red blood cell count, white blood cell with differential and platelet count. Differential included neutrophils, bands, lymphocytes, monocytes, eosinophils, and basophils. The intensity of each hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAEs). Hematological toxicities are summarized by Common Terminology Criteria (CTC) V3.0 Maximum Toxicity Grade. (NCT00316186)
Timeframe: Week 1 through Endpoint (variable based on disease progression or toxicity

Interventionparticipants (Number)
AnemiaNeutropeniaThrombocytopeniaLeukopenia
Intravenous Topotecan and Carboplatin144510

[back to top]

Adverse Events That Led to Discontinuation of Bevacizumab

Any treatment-emergent adverse event leading to study treatment discontinuation (NCT00318136)
Timeframe: First bevacizumab administration until 60 days after discontinuation of bevacizumab or death

InterventionPatients (Number)
Cerebral InfarctionCerebral IschemiaNeuropathy PeripheralDeep Vein ThrombosisHypertensionDyspneaPulmonary EmbolismCardiac Failure CongestiveProteinuria
Treated With Bevacizumab111211111

[back to top]

Progression-free Survival

"Progression-free survival (PFS) was defined as the time from enrollment to the time of documented disease progression or death from any cause, whichever occurred earlier. PFS was determined for only those patients that received bevacizumab.~Summary of PFS (median) was estimated from Kaplan-Meier curve. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley." (NCT00318136)
Timeframe: Length of study

InterventionMonths (Median)
Treated With Bevacizumab6.2

[back to top]

Selected Adverse Events

"Selected treatment-emergent adverse events for any grade of pulmonary hemorrhage, any grade of non-pulmonary hemorrhage, any grade of gastrointestinal perforation, Grade ≥ 2 arterial thromboembolic events, Grade ≥ 2 left ventricular systolic dysfunction, Grade ≥ 3 proteinuria, and Grade ≥ 3 hypertension. Refer to NCI CTCAE v.3 for grading definitions.~Serious adverse events (SAEs) occurring in any of the above categories are included. See the Serious Adverse Events section below for full SAE reporting." (NCT00318136)
Timeframe: First bevacizumab administration until 60 days after discontinuation of bevacizumab or death

InterventionPatients (Number)
Any grade of pulmonary hemorrhageAny grade of non-pulmonary hemorrhageAny grade of gastrointestinal perforationGrade ≥ 2 arterial thromboembolic eventsGrade ≥ 2 left ventricular systolic dysfunctionGrade ≥ 3 proteinuriaGrade ≥ 3 hypertension
Treated With Bevacizumab2002115

[back to top]

Incidence of Grade ≥3 Pulmonary Hemorrhage Adverse Events

"To estimate the rate of National Cancer Institute Common Terminology for Adverse Events (NCI CTCAE), Version 3.0, Grade ≥3 pulmonary hemorrhage adverse events. Per NCI CTCAE v.3: Grade 3 = Transfusion, interventional radiology, endoscopic, or operative intervention indicated; radiation therapy (i.e., hemostasis of bleeding site); Grade 4 = Life-threatening consequences; major urgent intervention indicated; Grade 5 = Death." (NCT00318136)
Timeframe: First bevacizumab administration until 60 days after discontinuation of bevacizumab or death

InterventionPercentage of patients (Number)
Treated With Bevacizumab3.2

[back to top]

Nausea

Number of patients with a nausea event. Based on the evaluable for-safety-population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel) (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib74
Carboplatin/Paclitaxel260

[back to top]

Neurotoxicity

Number of patients with a neurotoxicity event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel) (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib30
Carboplatin/Paclitaxel411

[back to top]

Vomiting

Number of patients with a vomiting event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel) (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib59
Carboplatin/Paclitaxel193

[back to top]

Symptom Improvement as Measured by the Lung Cancer Subscale (LCS) of the FACT-L Questionnaire

Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in LCS score (from baseline) of 2 or more, and there were no intervening visits showing a decrease from baseline of 2 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit (NCT00322452)
Timeframe: FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.

InterventionParticipants (Number)
Gefitinib304
Carboplatin/Paclitaxel272

[back to top]

Rashes/Acnes

Number of patients with a rashes/acnes event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel) (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib398
Carboplatin/Paclitaxel132

[back to top]

Objective Tumour Response Rate According to RECIST

Number of participants with an objective response. An objective response (OR) was defined as a patient having a best overall response of either complete response (CR) or partial response (PR) according to RECIST, confirmed at least 28 days following the date of the initial response. (NCT00322452)
Timeframe: Tumour assessments as per RECIST were performed at baseline and then every 42 days ± 7 days from randomization until data cut off (14th April 2008).

InterventionParticipants (Number)
Gefitinib262
Carboplatin/Paclitaxel196

[back to top]

Quality of Life (QoL) as Measured by the Total Score of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire

Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in FACT-L score (from baseline) of 6 or more, and there were no intervening visits showing a decrease from baseline of 6 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit (NCT00322452)
Timeframe: FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.

InterventionParticipants (Number)
Gefitinib283
Carboplatin/Paclitaxel229

[back to top]

Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Anaemia

Number of patients with an anaemia event, identified from the lab data as a worsening in haemoglobin from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel). (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib11
Carboplatin/Paclitaxel56

[back to top]

Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Liver Transaminases

Number of patients with an elevated liver transaminase event, identified from the lab data as a worsening in ALT or AST from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel). (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib57
Carboplatin/Paclitaxel6

[back to top]

Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Neutropenia

Number of patients with a neutropenia event, identified from the lab data as a worsening in absolute neutrophil count from baseline to a CTC grade 3 or above which Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel). (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib4
Carboplatin/Paclitaxel385

[back to top]

Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Leukopenia

Number of patients with a leukopenia event, identified from the lab data as a worsening in white blood cell count from baseline to a CTC grade 3 or above. Based on the evaluable for-safety-population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel). (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib1
Carboplatin/Paclitaxel202

[back to top]

Common Toxicity Criteria (CTC) Grade 3, 4, or 5 Thrombocytopenia

Number of patients with a thromboctyopenia event, identified from the lab data as a worsening in platelet count from baseline to a CTC grade 3 or above. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel). (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib5
Carboplatin/Paclitaxel29

[back to top]

Diarrhoea

Number of patients with a diarrhoea event. Based on the evaluable-for-safety population, which included all patients who received at least 1 dose of study medication (gefitinib, or carboplatin or paclitaxel) (NCT00322452)
Timeframe: Includes events that occurred whilst a patient was receiving first-line randomized treatment: defined as date of first dose to date of last dose +1 day for gefitinib, and date of first infusion to date of last infusion + 21 days for carboplatin/paclitaxel

InterventionParticipants (Number)
Gefitinib274
Carboplatin/Paclitaxel128

[back to top]

Median Overall Survival (OS) in Months at OS Data Cut Off (14th June 2010)

Overall Survival was assessed via calculation of the time to death due to any cause. If a participant was known to have died, the time to death was defined as the time from the date of randomization to the date of death. Otherwise, a participant was censored at the last date they were known to be alive. Median Overall Survival in months is presented here. (NCT00322452)
Timeframe: Following the PFS DCO on 14th April 2008 information on survival status was collected every 8 weeks.

InterventionMonths (Median)
Gefitinib18.8
Carboplatin/Paclitaxel17.4

[back to top]

Quality of Life (QoL) as Measured by the Trial Outcome Index (TOI) of the Functional Assessment of Cancer Therapy - Lung Cancer (FACT-L) Questionnaire

Number of patients improving: a patient was described as improved if they had 2 visits (at least 21 days apart) where there was an increase in TOI score (from baseline) of 6 or more, and there were no intervening visits showing a decrease from baseline of 6 or more. Includes all patients with QoL data at baseline & at least 1 post-baseline visit (NCT00322452)
Timeframe: FACT-L data were collected at baseline, week 1, every 3 weeks (from baseline) until day 127, then every 42 days until the patient was confirmed as having objectively progressed (via RECIST), and at treatment discontinuation.

InterventionParticipants (Number)
Gefitinib274
Carboplatin/Paclitaxel184

[back to top]

Median Progression Free Survival (PFS) in Months

PFS was defined as the interval from the date of randomization to the date of objective disease progression (as per RECIST) or the date of death (from any cause) in the absence of objective disease progression. The median PFS in months is presented here. (NCT00322452)
Timeframe: Tumour assessments as per RECIST were performed at baseline and then every 42 days ± 7 days from randomization until data cut off (14th April 2008).

InterventionMonths (Median)
Gefitinib5.7
Carboplatin/Paclitaxel5.8

[back to top]

Therapy Completion Rate

The therapy completion rate is the proportion of patients who completed 6 cycles of carboplatin/paclitaxel therapy without dose reductions. (NCT00322881)
Timeframe: 6 cycles of therapy, up to approximately 4.5 months given the cycle length of 21 days.

Interventionproportion of participants (Number)
Carboplatin/Paclitaxel.50

[back to top]

Stable Disease (SD)

Number of subjects with SD per RECIST criteria (NCT00323869)
Timeframe: 6 weeks

Interventionparticipants (Number)
Bevacizumab + Carboplatin + Gemcitabine34

[back to top]

Response Rate (CR + PR + SD)

"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions, by computed tomography (CT); bone scan; positron emission tomography (PET) scan; and/or magnetic resonance imaging (MRI) as necessary to assess diseasE~Response determined as the number of subjects with any clinical response (CR + PR + SD) per RECIST criteria.~Complete Response (CR) = disappearance of all target lesions~Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions~Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, or appearance of new cancer lesions~Stable Disease (SD): No significant effect, does not meet criteria for PR or PD." (NCT00323869)
Timeframe: 6 weeks

Interventionparticipants (Number)
Bevacizumab + Carboplatin + Gemcitabine41

[back to top]

Progression-free Survival (PFS)

Median progression-free survival (PFS) was assessed as the time to disease progression; toxicity requiring treatment discontinuation; or death. (NCT00323869)
Timeframe: 18 months

Interventionmonths (Median)
Bevacizumab + Carboplatin + Gemcitabine8.7

[back to top]

Time-to-First Event

Median time-to-first event, with events defined as disease progression, death, or toxicity requiring drug discontinuation (NCT00323869)
Timeframe: 18 months

Interventionmonths (Median)
Bevacizumab + Carboplatin + Gemcitabine6.4

[back to top]

Partial Response (PR)

Number of subjects with PR per RECIST criteria (NCT00323869)
Timeframe: 6 weeks

Interventionparticipants (Number)
Bevacizumab + Carboplatin + Gemcitabine7

[back to top]

Overall Survival (OS) at 12 Months

Number of subjects surviving 1 year after treatment initiation (NCT00323869)
Timeframe: 12 months

Interventionparticipants (Number)
Bevacizumab + Carboplatin + Gemcitabine27

[back to top]

Overall Survival (OS)

To evaluate the safety of the combination regimen. (NCT00323869)
Timeframe: 36 months

Interventionmonths (Median)
Bevacizumab + Carboplatin + Gemcitabine12.8

[back to top]

Complete Response (CR)

Number of subjects with CR per RECIST criteria (NCT00323869)
Timeframe: 6 weeks

Interventionparticipants (Number)
Bevacizumab + Carboplatin + Gemcitabine0

[back to top]

Overall Survival (OS) at 24 Months

Number of subjects surviving 2 years after treatment initiation (NCT00323869)
Timeframe: 24 months

Interventionparticipants (Number)
Bevacizumab + Carboplatin + Gemcitabine5

[back to top]

Duration of Response (DOR)

DOR-RECIST criteria of (Complete Response [CR =Disappearance of lesions] or Partial Response [PR=≥30% size decrease of lesions]) is defined as time from the date when measurement criteria are met for CR or PR until the date of first observation of progressive disease (PD) or death from study disease. For participants who die from causes other than study disease and without PD, DOR will be censored at the date of death. For participants who have not died as of the data cut-off date who are without PD, DOR was censored at last contact date. (NCT00325234)
Timeframe: Time of response to progressive disease (up to 19 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin7.7
Gemcitabine/Vinorelbine7.5

[back to top]

Time to Progressive Disease (PD)

Time to PD is defined as the time from the date of study enrollment to the first documented date of PD or death from study disease. For participants who die from causes other than study disease and without PD, time to PD was censored at the date of death. For participants not known to have died as of the data cut-off date and do not have PD, time to PD was censored at the last contact date. For participants who received subsequent chemotherapy (after discontinuation from the study chemotherapy) prior to disease progression, time to PD was censored at the date of subsequent chemotherapy. (NCT00325234)
Timeframe: Baseline to measured PD (up to 25.1 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin5.1
Gemcitabine/Vinorelbine5.6

[back to top]

Time to Response

Time to response (Complete Response(CR) or Partial Response (PR) is defined as the time from the date of study enrollment to the first date when the measurement criteria are met for complete response or partial response (whichever status is recorded first). CR=Disappearance of target lesions lesions. PR=≥30% size decrease of lesions. (NCT00325234)
Timeframe: Baseline to response (up to 7.8 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin1.8
Gemcitabine/Vinorelbine1.8

[back to top]

Tumor Response Rate

Participants with best overall response determined from complete response (CR) or partial response (PR) according to Response Criteria in Solid Tumors (RECIST) criteria. For CR or PR, best response must be confirmed. A second assessment performed at 28 days. Two determinations of CR before progression required for rate to=CR. Evaluations include: CR=Disappearance of lesions. PR=≥30% size decrease of lesions. Progressive Disease (PD)=≥20% size increase of lesions. Stable Disease (SD)=Not enough shrinkage for PR nor enough increase for PD. Overall Response Rate=PR+CR/Qualified Participants*100. (NCT00325234)
Timeframe: Baseline up to 30 days of follow-up after 21 cycles of treatment

,
Interventionpercentage of participants (Number)
Overall ResponseComplete ResponsePartial ResponseStable DiseaseProgressive DiseaseUnknown
Gemcitabine/Vinorelbine29.53.326.234.427.98.2
Pemetrexed/Carboplatin26.60.026.635.926.610.9

[back to top]

Number of Participants With Adverse Events (AE)

A listing of adverse events is presented in the Reported Adverse Event Module. (NCT00325234)
Timeframe: every cycle up to twenty-one 21-day cycles (plus 30 days of follow-up)

,
Interventionparticipants (Number)
Adverse EventsSerious Adverse Events
Gemcitabine/Vinorelbine6622
Pemetrexed/Carboplatin6418

[back to top]

Time To Treatment Failure (TTTF)

TTTF is defined as the time from date of study enrollment to the first documented date of death, PD, or study treatment discontinuation due to adverse event (AE). For participants not known to have discontinued as of the data cut-off date, TTTF is censored at the last contact date. For participants who discontinued for reasons other than death, PD, or AE, TTTF is censored at the date of discontinuation. (NCT00325234)
Timeframe: Baseline to end of treatment (up to 21.9 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin4.8
Gemcitabine/Vinorelbine5.1

[back to top]

Overall Survival at 1 Year After Randomization (Phase II Patients Only)

Overall survival was defined as the time from study enrollment to the time of death from any cause. A patient is classified as a success if alive at 1 year. (NCT00326599)
Timeframe: 1 year

Interventionpercentage of participants (Number)
Phase II: Arm I (Cediranib + Gemcitabine + Carboplatin)48
Phase II: Arm II (Gemcitabine + Carboplatin)41

[back to top]

Progression-free Survival (Phase II Patients Only)

Progression-free survival was defined as the time from study enrollment to the first date of disease progression or death as a result of any cause, whichever occurs first. Progression-free survival will be censored at the date of the last contact for patients who are still alive and who have not had disease progression. (NCT00326599)
Timeframe: Up to 5 years

Interventionmonths (Median)
Phase II: Arm I (Cediranib + Gemcitabine + Carboplatin)6.3
Phase II: Arm II (Gemcitabine + Carboplatin)4.5

[back to top]

Progression-free Survival Rate at 6 Months After Randomization (Phase II Patients Only)

"Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). A patient is classified as a success if alive and progression-free at 6 months.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions." (NCT00326599)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Phase II: Arm I (Cediranib + Gemcitabine + Carboplatin)48
Phase II: Arm II (Gemcitabine + Carboplatin)38

[back to top]

Time to Treatment Failure (Phase II Patients Only)

Time to treatment failure was defined to be the time from date of registration to the date at which the patient was removed from the treatment due to progression, toxicity, refusal or death from any cause. (NCT00326599)
Timeframe: Up to 15 months

Interventionmonths (Median)
Phase II: Arm I (Cediranib + Gemcitabine + Carboplatin)2.48
Phase II: Arm II (Gemcitabine + Carboplatin)2.89

[back to top]

Confirmed Response Rate (Complete Response and Partial Response) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II Patients Only)

"A confirmed tumor response was defined as a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 6 weeks apart.~Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:~Complete Response (CR): disappearance of all target lesions;~Partial Response (PR) 30% decrease in sum of longest diameter of target lesions" (NCT00326599)
Timeframe: Up to 5 years

Interventionpercentage of participants (Number)
Phase II: Arm I (Cediranib + Gemcitabine + Carboplatin)19
Phase II: Arm II (Gemcitabine + Carboplatin)20

[back to top]

Dose Limiting Toxicity (DLT) (Lead-in Phase Arm I Patients Only)

DLT was defined as an adverse event occurring in cycle 1 only, at least possibly attributed to the study treatment and meeting the following criteria: 1) Grade 4 absolute neutrophil count (ANC) >5 days or of any duration with fever >38.5 degree Celsius; 2) Grade 4 platelet count; 3) Grade 3 or higher non-hematologic toxicities (for nausea, vomiting or diarrhea, grade 3 toxicities will be DLT if they occur despite maximal use of anti-emetic support or anti-diarrhea agents, respectively); 4) Cediranib dose interruption of >14 days for drug-related toxicities. (NCT00326599)
Timeframe: Cycle 1 (up to 3 weeks)

Interventionparticipants (Number)
Lead-in Phase: Arm I (Cediranib + Gemcitabine + Carboplatin)1

[back to top]

Overall Survival (Phase II Patients Only)

Overall survival was defined as the time from study enrollment to the time of death from any cause. Overall survival will be censored at the date of the last follow-up visit for patients who are still alive or lost to follow-up. (NCT00326599)
Timeframe: Up to 5 years

Interventionmonths (Median)
Phase II: Arm I (Cediranib + Gemcitabine + Carboplatin)12.0
Phase II: Arm II (Gemcitabine + Carboplatin)9.9

[back to top]

6-month Progression-free Survival

Measured from the date of registration to the first of progression or death due to any cause with patients last known to be alive and progression-free censored at the date of last contact (NCT00329641)
Timeframe: Every 6 weeks for the first 8 cycles of therapy, and then every 9 weeks until disease progression for up to 3 years after registration or until death

InterventionPercent of population (Number)
Sorafenib, Carboplatin, Paclitaxel29

[back to top]

One-year Overall Survival

Measured from date of registration to study until death due to any caused with observations last known to be alive censored at the date of last contact (NCT00329641)
Timeframe: Every 6-9 weeks until progression, after progression every six months for first two years and annually thereafter up to 3 for up to 3 years after registration or until death

InterventionPercentage of population (Number)
Sorafenib, Carboplatin, Paclitaxel42

[back to top]

Response Rate (Complete and Partial Response)

Complete response corresponds to complete disappearance of all measurable and non-measurable lesions with no new lesions. Partial response corresponds to greater than or equal to 30fi decrease of sum of longest diameter of all target measurable lesions with no new lesion and non unequivocal progression of non-measurable disease. (NCT00329641)
Timeframe: Every 6 weeks for the first 8 cycles of therapy, then every three cycles (9 weeks) until progression

Interventionparticipants (Number)
Sorafenib, Carboplatin, Paclitaxel0

[back to top]

Toxicity

Number of patients with Grade 3-5 adverse events that are related to study drug by given type of adverse event (NCT00329641)
Timeframe: Weekly during the first cycle of therapy, then prior to each cycle (one cycle = 3 weeks)

InterventionParticipants with a given type of AE (Number)
Calcium, serum-low (hypocalcemia)CataractDiarrheaFatigue (asthenia, lethargy, malaise)Febrile neutropeniaHemoglobinInfec w/ Gr 3/4 neut-Urinary tractLeukocytes (total WBC)LymphopeniaMucositis/stomatitis (func/symp) - PharynxNeuropathy: sensoryNeutrophils/granulocytes (ANC/AGC)PlateletsPruritus/itchingRash/desquamationVision-blurred vision
Intervention11211214212104151

[back to top]

Patients' Overall Tumor Response as Measured by Response Evaluation Criteria in Solid Tumors (RECIST)

Best response recorded from start of treatment until after 4th cycle of treatment. Defined by the sum of Complete Responses (CR), Partial Responses (PR), and Stable Disease (SD) in patients neoadjuvant chemotherapy. CR=disappearance of all lesions, PR=>or=30% decrease in sumof all target lesins, Progressive Disease (PD) =>or =20% increase in sum of all target or any new lesions, SD=not CR, PR or PD. (NCT00331422)
Timeframe: Week 16 (4 weeks after 4th course)

InterventionParticipants (Number)
Partial ResponseProgressive DiseaseStable Disease
Patients Who Received Treatment232

[back to top]

Number of Patients Who Underwent Optimal Cytoreduction After Chemotherapy

These patients had their tumor(s) removed by surgery after receiving 4 cycles of chemotherapy to determine their response. (NCT00331422)
Timeframe: Week 18 (After 4 cycles of chemotherapy)

InterventionParticipants (Number)
Evaluable Patients (Received 4 Cycles of Therapy and Surgery)2

[back to top]

Clinical Response Based on Serum Cancer Antigen 125 (CA-125) Concentration

Ca-125 serum results compared from baseline to after patient's last treatment. This is a tumor biomarker. A decrease in results indicates a clinical response. (NCT00331422)
Timeframe: From Baseline to up to 12 weeks (4 courses of therapy)

InterventionParticipants (Number)
Increased ConcentrationDecreased Concentration
Patients Who Received Treatment16

[back to top]

Long-term Survival of Patients With Stage I-IV Malignant Rhabdoid Tumors

The outcome of these patients will be compared with a fixed outcome based on that seen for similar patients treated with NWTS-5 regimen (NCT00002610). (NCT00335556)
Timeframe: 4 years

InterventionPercentage of 4-year OS (Number)
UH-138.9

[back to top]

Number of Patients With INI1 Mutations in Renal and Extrarenal Malignant Rhabdoid Tumor by Fluorescent in Situ Hybridization

(NCT00335556)
Timeframe: At baseline

InterventionCount participants (Number)
UH-123
Window/UH-11

[back to top]

Event-Free Survival of Patients With Diffuse Anaplastic Wilms' Tumor (DAWT)

Compare the outcome of patients treated with alternating CyCE/VDCy chemotherapy (with or without vincristine/irinotecan cycles) to a fixed outcome based on that seen for similar patients treated with NWTS-5 (NCT00002610). (NCT00335556)
Timeframe: 4 years

InterventionPercentage of 4-year OS (Number)
UH-176.1
Window/UH-125.0
UH-287.5

[back to top]

Event Free Survival Probability

Event-free survival will be informally compared to that seem for similar patients treated on NWTS-5 (NCT00002610). (NCT00335556)
Timeframe: 4 years

InterventionPercent Probability 4 Year EFS (Number)
Regimen DD-4A100.0

[back to top]

Toxicity Rate

Percentage of participants with Grade 4 cardiac toxicities, Grade 4 Sinusoidal Obstruction Syndrome (SOS), and treatment-related deaths determined using CTCAE v4. (NCT00335556)
Timeframe: Up to 4 years

InterventionPercentage of patients (Number)
Cardiac toxicitiesTreatment-related deathsSinusoidal Obstruction Syndrome
Combined UH-2, UH-1, Window/UH-14.94.90

[back to top]

Response Rate

Criteria for response assessed by three-dimensional measurement: Complete Response (CR), Disappearance of all index lesions and non-index lesions. No new lesions; Partial Response (PR), At least a 65% decrease in the sum of the volumes of the index lesions. No new lesions; Response rate (RR) = CR+PR of patients who received window therapy. (NCT00335556)
Timeframe: Up to 2 months

InterventionPercentage of participants (Number)
Combined Window/UH-1 and UH-271

[back to top]

Toxicity As Assessed By the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

Number of patients assigned chemotherapy who experienced grade 3 or higher CTC AE toxicity. (NCT00335738)
Timeframe: During planned six cycles of chemotherapy

Interventionparticipants (Number)
Group 1 (Identified by Central Review as High Risk)19

[back to top]

Pathological Features Present At Diagnosis - Tumor Involving the Optic Nerve Posterior to the Lamina Cribrosa (LC) as an Independent Finding

Proportion of patients with tumor involving the optic nerve posterior to the lamina cribrosa as an independent. (NCT00335738)
Timeframe: At enrollment

InterventionProportion of patients with LC (Number)
All Patients0.16

[back to top]

Pathological Features Present at Diagnosis - Scleral Invasion (SI)

Proportion of patients that had scleral invasion at enrollment. (NCT00335738)
Timeframe: At enrollment

InterventionProportion of patients with SI (Number)
All Patients0.016

[back to top]

Pathological Features Present At Diagnosis - Posterior Uveal Invasion (PVI)

Proportion of patients who had posterior uveal invasion at enrollment. (NCT00335738)
Timeframe: At enrollment

InterventionProportion of patients with PVI (Number)
All Patients0.24

[back to top]

Pathological Features Present At Diagnosis - Iris Infiltration (II)

Proportion of patients who had iris infiltration at enrollment. (NCT00335738)
Timeframe: At enrollment

InterventionProportion of patients with II (Number)
All Patients0.029

[back to top]

Pathological Features Present At Diagnosis - Anterior Chamber Seeding (ACS)

Proportion of patients who had anterior chamber seeding at enrollment. (NCT00335738)
Timeframe: At enrollment

InterventionProportion of patients with ACS (Number)
All Patients0.045

[back to top]

Overall Survival (OS)

OS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone. (NCT00335738)
Timeframe: At 2 Years

InterventionEstimated Probability (Number)
Group 1 (Identified by Central Review as High Risk)0.9628
Group 2 (Identified by Central Review as Not High Risk)1

[back to top]

Event-free Survival (EFS)

EFS distributions will be estimated by the Kaplan-Meier method for patients with high risk features according to central review and treated with adjuvant chemotherapy and separately for subjects with central review recommendation of enucleation alone. (NCT00335738)
Timeframe: At 2 years

InterventionEstimated Probability (Number)
Group 1 (Identified by Central Review as High Risk)0.9394
Group 2 (Identified by Central Review as Not High Risk)0.9953

[back to top]

Pathological Features Present At Diagnosis - Ciliary Body Infiltration (CBI)

Proportion of patients who had ciliary body infiltration at enrollment. (NCT00335738)
Timeframe: At Enrollment

InterventionProportion of patients with CBI (Number)
All Patients0.019

[back to top]

Percentage of Participants With Any Acute Adverse Events

Event is defined as the first occurrence of any acute toxicity. Estimates will be obtained using life-table methods. Patients who have progression or recurrence of disease will be censored in this analysis. Difference in incidence for the two treatment regimens will be compared using log-rank test. (NCT00336024)
Timeframe: Beginning of treatment to the end of consolidation

Interventionpercentage of participants (Number)
Arm I (Patients Treated Without Methotrexate (MTX))97.4
Arm II (Patients Treated With MTX)97.2

[back to top]

Median/Range of Patients for Total Quality of Life (QOL) Score, Intelligence Quotient (IQ) and Processing Speed Index (PSI).

"Three tools are used to assess intelligence (IQ) depending on age. The range of IQ scores is 40-160 (mean=100, SD=15); range for the Processing Speed Index (PSI)=45-155. Higher scores represent better functioning. (1) Wechsler Preschool and Primary Scale of Intelligence-4th Edition (WPPSI-IV) is used for ages 2.5 to 6 years. Bug Search and Cancellation subtests are summed to calculate PSI. (2) Wechsler Intelligence Scales for Children-5th Edition (WISC-V) is used for ages 6 - 16 years. Symbol Search and Coding subtests are summed to calculate PSI. (3) Wechsler Adult Intelligence Scales-4th Edition (WAIS-IV) is used for ages 16 and older. Symbol Search and Coding subtests are summed to calculate PSI.~The Pediatric Quality of Life Inventory Version 4 (PedsQL) measures health-related quality of life (QOL). Parents complete the measure for children ages 2-17, and patients > 18 complete a self-report version. Total scores range from 0-100, with higher scores representing better QOL." (NCT00336024)
Timeframe: 60 months (+/- 3 months)

,
Interventionscores on a scale (Median)
Total Quality of Life ScoreIntelligence QuotientProcessing Speed Index
Arm I (Patients Treated Without Methotrexate (MTX))60.577.082.0
Arm II (Patients Treated With MTX)56.578.589.0

[back to top]

Number of Participants With Secondary Malignancies

The number of patients who had secondary malignancy will be reported for this analysis due to small numbers. (NCT00336024)
Timeframe: Off-treatment up to 9 years

InterventionParticipants (Count of Participants)
Arm I (Patients Treated Without Methotrexate (MTX))1
Arm II (Patients Treated With MTX)0

[back to top]

Rates of Nutritional Toxicities

Rates of nutritional toxicities reported as Adverse Events during therapy for each cycle will be summarized using standard descriptive methods (such as number of patients). The difference in number of patients with nutritional toxicities between the two treatment regimens will be compared using a Chi-square test. (NCT00336024)
Timeframe: Beginning of treatment to the end of consolidation

,
InterventionParticipants (Count of Participants)
Nutritional Disorders Induction Cycle INo Nutritional Disorders Induction Cycle INutritional Disorders Induction Cycle IINo Nutritional Disorders Induction Cycle IINutritional Disorders Induction Cycle IIINo Nutritional Disorders Induction Cycle IIINutritional Disorders Consolidation Cycle INo Nutritional Disorders Consolidation Cycle INutritional Disorders Consolidation Cycle IINo Nutritional Disorders Consolidation Cycle IINutritional Disorders Consolidation Cycle IIINo Nutritional Disorders Consolidation Cycle III
Arm I (Patients Treated Without Methotrexate (MTX))1029132673212279301029
Arm II (Patients Treated With MTX)172113251226830533533

[back to top]

Number of Participants With Chronic Central Hypothyroidism

"Thyroid function was assessed as per ACNS0334 Endocrine Guidelines. Normal and Abnormal are defined at each institution by the laboratory standards where the blood tests are run. Central Hypothyroidism is defined as Free T4 level less than Institutional Normal with TSH less than or equal to Institutional Normal." (NCT00336024)
Timeframe: Off-treatment up to 9 years

InterventionParticipants (Count of Participants)
Arm I (Patients Treated Without Methotrexate (MTX))1
Arm II (Patients Treated With MTX)1

[back to top]

Rates of Gastrointestinal Toxicities

Rates of gastrointestinal toxicities reported as Adverse Events during therapy for each cycle will be summarized using standard descriptive methods (such as number of patients). The difference in number of patients with gastrointestinal toxicities between the two treatment regimens will be compared using a Chi-square test. (NCT00336024)
Timeframe: Beginning of treatment to the end of consolidation

,
InterventionParticipants (Count of Participants)
GI Tox Induction Cycle INo GI Tox Induction Cycle IGI Tox Induction Cycle IINo GI Tox Induction Cycle IIGI Tox Induction Cycle IIINo GI Tox Induction Cycle IIIGI Tox Consolidation Cycle INo GI Tox Consolidation Cycle IGI Tox Consolidation Cycle IINo GI Tox Consolidation Phase IIGI Tox Consolidation Cycle IIINo GI Tox Consolidation Cycle III
Arm I (Patients Treated Without Methotrexate (MTX))8314354351128732534
Arm II (Patients Treated With MTX)1226102883014241028632

[back to top]

Number of Participants With Chronic Diabetes Insipidus

"The number of patients who had Diabetes Insipidus and on DDAVP will be reported for this analysis due to small numbers.." (NCT00336024)
Timeframe: Beginning of off-treatment to up to 9 years

InterventionParticipants (Count of Participants)
Arm I (Patients Treated Without Methotrexate (MTX))1
Arm II (Patients Treated With MTX)1

[back to top]

Number of Participants With Chronic Low Somatomedin C

Low Somatomedin C is defined as patients with somatomedin C value less than institutional normal. As numbers are too small, descriptive statistics such as number will be reported for this analysis. Growth hormone function was assessed as per ACNS0334 Endocrine Guidelines. Low Somatomedin C levels are defined at each institution by the laboratory standards where the blood tests are run. (NCT00336024)
Timeframe: Off-treatment up to 9 years

InterventionParticipants (Count of Participants)
Arm I (Patients Treated Without Methotrexate (MTX))2
Arm II (Patients Treated With MTX)5

[back to top]

Number of Participants With Chronic Primary Hypothyroidism/Subclinical Compensatory HypothyroidismHypothyroidism/Subclinical Compensatory Hypothyroidism

"Thyroid function was assessed as per ACNS0334 Endocrine Guidelines. Normal and Abnormal are defined at each institution by the laboratory standards where the blood tests are run. Primary Hypothyroidism/Subclinical Compensatory Hypothyroidism is defined as patients with Free T4 level less than Institutional Normal or equal to Institutional Normal with TSH level greater than Institutional Normal." (NCT00336024)
Timeframe: Off-treatment up to 9 years

InterventionParticipants (Count of Participants)
Arm I (Patients Treated Without Methotrexate (MTX))3
Arm II (Patients Treated With MTX)5

[back to top]

Percentage of Participants With Event Free Survival (EFS)

EFS was defined as time from enrollment to the occurrence of first event (disease progression/relapse, secondary malignancy, death from any cause) or date of last contact for patients who are event-free. The percentage of participants with EFS and 90% confidence interval were provided. The difference in incidence for the two treatment regimens were compared using a one-sided log-rank test with a significance level of 0.1. (NCT00336024)
Timeframe: Baseline to up to 5 years

Interventionpercentage of participants with EFS (Number)
Arm I (Patients Treated Without Methotrexate (MTX))43.6
Arm II (Patients Treated With MTX)54.9

[back to top]

Clinical Complete Response Rate of This Regimen in the Population

What is the the complete response (CR) rate at the completion of therapy. (NCT00343083)
Timeframe: 3 months

Interventionpercentage of participants (Number)
Concurrent Chemo Raditaion Wtih Cetuximab84

[back to top]

Local Regional Control at 2 Years

(NCT00343083)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Concurrent Chemo Raditaion Wtih Cetuximab72

[back to top]

Pathological Response to Cetuximab

Adding CTX to weekly PC and daily RT. CBC and Chemistry panel blood testing (NCT00343083)
Timeframe: 2 years

Interventionparticipants (Number)
Concurrent Chemo Raditaion Wtih Cetuximab43

[back to top]

The Primary Endpoint is the Local Regional Control Rate Assessed 3 Months Post Completion of Radiation Therapy.

The local regional control rate was assessed 3 months post completion of radiation therapy based on either MRI or CT and clinical exam. (NCT00343083)
Timeframe: 3 months

Interventionparticipants (Number)
Concurrent Chemo Raditaion Wtih Cetuximab43

[back to top]

Overall Survival and Disease-free Survival

(NCT00343083)
Timeframe: 3 years (overall) 2 years disease-free

Interventionpercentage of participants (Number)
overall survivaldisease-free survival
Concurrent Chemo Raditaion Wtih Cetuximab5958

[back to top]

Percentage of Participants With Grade 3 Toxicities of Cetuximab

"One of the more serious side effects of cetuximab therapy is the incidence of acne-like rash. This rash rarely leads to dose reductions or termination of therapy. It is generally reversible.~Further severe infusion reactions include but are not limited to: fevers, chills, rigors, urticaria, pruritis, rash, hypotension, N/V, HA, bronchospasm, dyspnea, wheezing, angioedema, dizziness, anaphylaxis, and cardiac arrest. Therefore, pretreatment with diphenhydramine 30-60 min. before administration is standard of care. Other common side effects include photosensitivity, hypomagnesemia due to magnesium wasting, and less commonly pulmonary and cardiac toxicity." (NCT00343083)
Timeframe: 9 weeks

Interventionpercentage of participants (Number)
mucositisrashleukopenianeutropeniaRT dermatisis
Concurrent Chemo Raditaion Wtih Cetuximab799191916

[back to top]

Progression Free Survival (PFS)

PFS is defined as the time from randomization until the date of progression of disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD ≥20% increase in sum of longest diameter of target lesions. Participants who are alive and without PD will be censored at the date of their last tumor assessment. (NCT00343291)
Timeframe: Randomization to PD or date of death from any cause up to 33.1 months

Interventionmonths (Median)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)6.05
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)4.50

[back to top]

Percentage of Participants Achieving an Objective Overall Response (Overall Response Rate)

The best objective overall response rate (ORR) is the percentage of randomized participants with a best overall response of complete response (CR) or partial response (PR), as classified by the investigator according to the RECIST guidelines. CR=disappearance of all target lesions; PR≥30% decrease in sum of longest diameter of target lesions. ORR is calculated as a total number of participants with CR or PR divided by the total number of participants treated in that arm, multiplied by 100. Participants with no post-baseline evaluation will be considered as a non-responder. (NCT00343291)
Timeframe: Randomization to measured progressive disease up to 31.8 months

Interventionpercentage of participants (Number)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)51.7
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)44.3

[back to top]

Duration of Overall Response

The duration of response, in participants with best overall response of CR or PR, is measured from the date criteria are met for CR/PR (whichever is first recorded), until the first date that the criteria for PD is met or death. CR, PR, and PD, as classified by the investigator according to the RECIST guidelines. CR=disappearance of all target lesions; PR≥30% decrease in sum of longest diameter of target lesions; PD≥20% increase in sum of longest diameter of target lesions. Participants who are alive and without PD will be censored at the date of their last tumor assessment. (NCT00343291)
Timeframe: Time of first response to the first date of PD or death due to any cause up to 31.8 months

Interventionmonths (Median)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)4.86
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)3.94

[back to top]

Overall Survival

Overall survival is defined as the time from randomization to death. Participants who are alive will be censored on the last known alive date. (NCT00343291)
Timeframe: Randomization to the date of death from any cause up to 42.7 months

Interventionmonths (Median)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)12.06
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)11.63

[back to top]

Percentage of Participants With Symptomatic Response (Symptom Response Rate)

Functional Assessment of Cancer Therapy for Patients With Lung Cancer (FACT-L) measures domains of health-related quality of life (HR-QL): physical wellbeing (WB), social/family WB, emotional WB, functional WB, and additional lung cancer concerns. Symptom response (improvement) was defined as ≥2 point increase from baseline in the 7-item Lung cancer subscale (LCS) score maintained for 2 consecutive assessments. Scores range from 0-28 with higher scores indicating fewer symptoms. Patients with a score of >26 were not evaluable for symptom response, since a score of 28 is the maximum possible. (NCT00343291)
Timeframe: From date of partial response until progression of disease up to 31.8 months

Interventionpercentage of participants (Number)
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/6)41.9
Cetuximab + Bevacizumab + Paclitaxel + Carboplatin (6/3)38.6

[back to top]

Progression Free Survival (PFS)

(NCT00345540)
Timeframe: From time of treatment start to time of disease progression

InterventionWeeks (Mean)
NOV-002 Plus Carboplatin19.4

[back to top]

Response Rate

(NCT00345540)
Timeframe: At treatment completion (8 weeks) and monthly until disease progression

InterventionParticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)
NOV-002 Plus Carboplatin0186

[back to top]

Safety of NOV-002 and Carboplatin

(NCT00345540)
Timeframe: Duration of trial and through 30-day follow-up period after final treatment

InterventionAdverse Events (Number)
CTC Grade 4 Adverse EventsCTC Grade 3 Adverse EventsCTC Grade 3 Related Adverse Events
NOV-002 Plus Carboplatin080

[back to top]

Time to Treatment Failure

Defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed. (NCT00350792)
Timeframe: baseline to stopping treatment (up to six 21-day cycles)

Interventionweeks (Mean)
Pemetrexed + Carboplatin12.95

[back to top]

Time to Treatment Failure

Defined as the time from study enrollment to the first observation of disease progression, death as a result of any cause, or early discontinuation of treatment. Time to treatment failure was censored at the date of the last follow-up visit for patients who did not discontinue early, who were still alive, and who have not progressed. (NCT00350792)
Timeframe: baseline to stopping treatment (up to six 21-day cycles)

Interventionweeks (Median)
Pemetrexed + Carboplatin16.0

[back to top]

Estimated Probability of One Year Progression-free Survival

Progression free survival (PFS) is the duration from enrollment until first disease progression or death. For patients not known to have died as of the data cut-off date and who do not have progressive disease, PFS is censored at the last radiological assessment date. (NCT00350792)
Timeframe: baseline to measured progressive disease or death, 1 year

Interventionpercentage of patients (Median)
Pemetrexed + Carboplatin13.1

[back to top]

Percentage of Participants With a Complete or Partial Tumor Response (Overall Tumor Response)

Tumor response is defined as the percentage of patients with either a complete response or a partial response. Response was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions and Partial Response=30% decrease in sum of longest diameter of target lesions. (NCT00350792)
Timeframe: baseline to measured objective tumor response (up to six 21-day cycles)

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin28.6

[back to top]

Overall Survival

Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. (NCT00350792)
Timeframe: baseline to date of death from any cause (up to 14.5 months)

Interventionmonths (Median)
Pemetrexed + Carboplatin10.4

[back to top]

Overall Survival (OS) Rate

"OS = time from patient registration to death of all causes~Estimated using Kaplan Meier" (NCT00352690)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Cohort 1 (First 12 Eligible Patients)73

[back to top]

Incidence and Severity of Radiation-induced Pneumonitis

(NCT00352690)
Timeframe: 30 days following completion of treatment (approximately 114 days)

Interventionparticipants (Number)
Grade 1Grade 2Grade 3Grade 4Grade 5
Cohort 1 (First 12 Eligible Patients)12100

[back to top]

Response Rates

Overall best response using RECIST 1.0 (NCT00352690)
Timeframe: 4 years

Interventionparticipants (Number)
Complete responsePartial responseProgressive diseaseUnknown
Cohort 1 (First 12 Eligible Patients)1511

[back to top]

Failure-free Survival (FFS)

The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first) (NCT00352690)
Timeframe: Completion of follow-up (follow-up ranged from 3 months to 6 years)

Interventionmonths (Median)
Cohort 1 (First 12 Eligible Patients)6

[back to top]

Failure-free Survival (FFS) Rate

"The time between patient registration and a failure event (progression, relapse, or death of all cause, whichever is first)~Estimated using Kaplan Meier" (NCT00352690)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Cohort 1 (First 12 Eligible Patients)44

[back to top]

Overall Survival (OS)

OS = time from patient registration to death of all causes (NCT00352690)
Timeframe: Completion of follow-up (follow-up ranged from 3 months to 6 years)

Interventionmonths (Median)
Cohort 1 (First 12 Eligible Patients)10.4

[back to top]

Incidence and Severity of Radiation-induced Esophagitis

(NCT00352690)
Timeframe: 30 days following completion of treatment (approximately 114 days)

Interventionparticipants (Number)
Grade 1Grade 2Grade 3Grade 4Grade 5
Cohort 1 (First 12 Eligible Patients)13000

[back to top]

Response

Anti tumor activity as assessed by computed tomography of neck/chest/abdomen/pelvis, positron emission tomography scan and/or gallium scan. Assessed by physical examination appropriate imaging studies. Bone marrow aspirate/biopsy must be normal and any macroscopic nodules in any organs detectable on imaging techniques should no longer be present. Gallium scans must be negative if initially positive. (NCT00354107)
Timeframe: Week 4

Interventionpercent (Number)
Treatment (Monoclonal Antibody Therapy, Chemotherapy)50

[back to top]

Objective Tumor Response

Best response recorded from the start of treatment until disease progression/recurrence using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response=disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that do not meet above criteria. (NCT00356525)
Timeframe: baseline to time of response (up to 17.5 months)

,,,
Interventionparticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseUnknown
Less Than One Year: Pemetrexed07322
Less Than One Year: Pemetrexed + Gemcitabine00920
One Year or Greater: Pemetrexed + Carboplatin02500
One Year or Greater: Pemetrexed + Gemcitabine01611

[back to top]

Overall Survival

Overall survival is the number of participants who were alive when the trial was terminated. (NCT00356525)
Timeframe: baseline to trial termination (17.5 months)

Interventionparticipants alive (Number)
Less Than One Year: Pemetrexed6
Less Than One Year: Pemetrexed + Gemcitabine4
One Year or Greater: Pemetrexed + Carboplatin6
One Year or Greater: Pemetrexed + Gemcitabine7

[back to top]

Progression-free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00360360)
Timeframe: 18 months

Interventionmonths (Median)
Bevacizumab/Paclitaxel/Carboplatin/Erlotinib8

[back to top]

Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

(NCT00360360)
Timeframe: 18 months

Interventionmonths (Median)
Bevacizumab/Paclitaxel/Carboplatin/Erlotinib12.6

[back to top]

Determine the Cause of Death of Patients After Treatment

To determine the cause of death (i.e., CNS tumor versus systemic disease progression) in patients after treatment. (NCT00362817)
Timeframe: up to 1 year

Interventionpatients (Number)
CNS tumorSystemic disease progression
Temozolomide & Intra-Arterial (IA) Carboplatin07

[back to top]

The Incidence and Severity of Centeral Nervous System (CNS) Toxicities

To determine the incidence and severity of CNS toxicity in patients treated with intra-arterial carboplatin and oral temozolomide. (NCT00362817)
Timeframe: up to 24 weeks

Interventionpatients (Number)
Temozolomide & Intra-Arterial (IA) Carboplatin0

[back to top]

Determine the Overall Survival of Patients

From the time of protocol initiation (NCT00362817)
Timeframe: up to 64 weeks

Interventionweeks (Mean)
Temozolomide & Intra-Arterial (IA) Carboplatin25.2

[back to top]

Analyze Patients Time to Progression

"Responses to treatment was determined by comparing new enhanced MRI scans with those obtained at the previous evaluation (i.e., 2 treatment cycles ago) or with the pre-IA chemotherapy baseline scan, if it is the first follow-up MRI scan during treatment.~MRI is the neuro-imaging modality of choice, since it is more accurate than CT for small tumors, multiple tumors, and tumors in the posterior fossa.58 The methodology used (techniques and equipment) must be identical for all scans. Lesions should be measured as the largest diameter seen on scan and the largest diameter perpendicular to that dimension." (NCT00362817)
Timeframe: up to 60 weeks

Interventionweeks (Mean)
Temozolomide & Intra-Arterial (IA) Carboplatin22.6

[back to top]

Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide

Response was evaluated by MRI Criteria (MacDonald Criteria). The MacDonald criteria for determining tumor progression is determined through assessing the increase in size of an enhancing tumor on consecutive MRI scans and clinical assessment. Complete response occurs when there is a disappearance of all enhancing tumor on consecutive MRI scans at least one month apart. Partial response occurs at a >50% reduction in size of enhancing tumor on consecutive MRI scans at least one month apart. Progressive disease occurs when there is a >25% increase in size of enhancing tumor on consecutive MRI scans. Stable disease occurs in all remaining situations. (NCT00362817)
Timeframe: up to 1 year

Interventionpercentage of patients with response (Number)
Temozolomide & Intra-Arterial (IA) Carboplatin42.8

[back to top]

Overall Survival

Overall survival is the duration from enrollment to death. For patients who are alive, overall survival is censored at the last contact. (NCT00363415)
Timeframe: baseline to date of death from any cause (up to 19.6 months)

Interventionmonths (Median)
Pemetrexed + Carboplatin8.1
Etoposide + Carboplatin10.6

[back to top]

Progression Free Survival

The period from study entry until disease progression, death or date of last contact. (NCT00363415)
Timeframe: baseline to measured progressive disease (up to 14.7 months)

Interventionmonths (Median)
Pemetrexed + Carboplatin3.8
Etoposide + Carboplatin5.4

[back to top]

Overall Survival (Subgroups)

The effects of individual baseline factors (sex, race, Eastern Cooperative Oncology Group (ECOG) performance, region, lactate dehydrogenase (LDH), age, number of metastatic sites, and history of brain metastases) on overall survival are reported. For two subgroups - LDH<=upper limit of normal and brain metastases=yes, the upper limits of the 95% confidence interval were not calculable for the etoposide+carboplatin group - instead the number of participants in these two subgroups are presented as a post-hoc outcome measure. (NCT00363415)
Timeframe: baseline to date of death from any cause (up to 19.6 months)

,
Interventionmonths (Median)
Sex: Male (n=325, n=330)Sex: Female (n=128, n=125)Race: Caucasian (n=391, n=379)Race: Non-Caucasian (n=62, n=76)ECOG: 0 or 1 (n=398, n=398)ECOG: 2 (n=54, n=55)Region: United States (n=92, n=83)Region: European Union (n=279, n=278)Region: Intercontinential Region (n=82, n=94)LDH: >Upper Limit of Normal (n=276, n=273)Age: <= 65 years (n=267, n=275)Age: >65 years (n=186, n=180)Number Metastatic Sites: <=2 (n=172, n=204)Number Metastatic Sites: >=3 (n=273, n=246)History of Brain Metastases: No (n=410, n=412)
Etoposide + Carboplatin10.411.611.28.711.35.211.311.29.99.311.59.711.510.310.6
Pemetrexed + Carboplatin8.28.18.27.18.56.28.18.57.27.28.47.710.07.78.2

[back to top]

Number of Participants in Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes

Number of participants with Low Density Lipoprotein <=upper limit of normal and the number of participants with a history of brain metastases. This post-hoc outcome replaces the one for Overall Survival (Subgroups: LDH<=Upper Limit of Normal and History of Brain Metastases=Yes). (NCT00363415)
Timeframe: baseline to date of death due to any cause (up to 19.6 months)

,
Interventionparticipants (Number)
LDH: <=Upper Limit of NormalHistory of Brain Metastases: Yes
Etoposide + Carboplatin16941
Pemetrexed + Carboplatin16743

[back to top]

Change From Baseline to Each Cycle in Functional Assessment of Cancer Therapy - Lung (FACT-L)

FACT-L measures following domains of health-related quality of life (HR-QL): physical well-being, social/family well-being, emotional well-being, functional well-being, and additional concerns of lung cancer. Total scores range from 0 to 136, with higher scores representing better HR-QL. A clinically meaningful change is considered to be 5 points. (NCT00363415)
Timeframe: baseline and 6 cycles (21-day cycles)

,
Interventionunits on a scale (Mean)
Baseline (n=384, n=383)Cycle 1 Change from Baseline (n=270, n=275)Cycle 2 Change from Baseline (n=283, n=310)Cycle 3 Change from Baseline (n=225, n=277)Cycle 4 Change from Baseline (n=199, n=259)Cycle 5 Change from Baseline (n=140, n=203)Cycle 6 Change from Baseline (n=98, n=146)
Etoposide + Carboplatin87.791.551.731.701.691.943.73
Pemetrexed + Carboplatin87.42-0.220.170.06-0.140.270.34

[back to top]

Disease-free Survival (DFS) Rate

"DFS was defined as the time from the administration of the first-dose of study medication until recurrence of tumor or death from any cause in the absence of previous documentation of tumor recurrence. DFS rate was the probability of being disease free and alive at a particular time. DFS rates were estimated using Kaplan-Meier Method, and 95% confidence intervals were computed using the method of Kalbfleisch and Prentice.~For participants who did have objective recurrence of tumor and who were still on study at the time of an analysis, or who were given antitumor treatment other than the study treatment, or who were removed from study follow-up prior to documentation of the tumor recurrence, DFS was censored at the last date the participant was known to be disease-free." (NCT00365365)
Timeframe: from the administration of the first-dose of study medication up to 12 months, 18 months and 24 months

,,
Interventionpercentage of participants (Number)
DFS rate at 12 monthsDFS rate at 24 monthsDFS rate at 36 months
Stratum 1 (AC->T + Bevacizumab)93.687.185.5
Stratum 2 (TAC + Bevacizumab)95.994.190.4
Stratum 3 (TCH + Bevacizumab).)98.296.390.4

[back to top]

Safety - Number of Participants With Adverse Events (AE)

"An adverse event was any untoward medical occurrence in a participant of the clinical investigation, regardless of the relationship to study treatment.~A serious adverse event (SAE) was an AE that at any dose (including overdose) resulted in death, was life-threatening, required inpatient hospitalization or prolonged existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect, and/or was medically important.~Treatment-emergent adverse events (TEAE) were defined as AEs that developed or worsened in severity during the on-treatment period." (NCT00365365)
Timeframe: from the administration of the first dose of study medication up to 30 days after the last dose of study medication; events ongoing at the time of discontinuation were monitored in the follow-up period until resolution.

,,
Interventionparticipants (Number)
with TEAEwith serious TEAEwith any TEAE leading to deathwith any TEAE leading to treatment discontinuationwith any Grade 3-4 Serious TEAE
Stratum 1 (AC->T + Bevacizumab)782302123
Stratum 2 (TAC + Bevacizumab)752422424
Stratum 3 (TCH + Bevacizumab).)59120169

[back to top]

Cardiac Safety - Number of Participants With Grade 3-4 Clinical Congestive Heart Failure (CHF)

"Participants were evaluated for clinical CHF every 3 weeks during chemotherapy, every 3 months while on maintenance therapy, and every 3 months during the 2-year follow-up period. Left ventricular ejection fraction (LVEF) of CHF was assessed by multi-gated acquisition (MUGA) or echocardiogram (ECHO) performed midway through completion of chemotherapy according to a treatment-specific schedule, every 12 weeks during maintenance therapy, and at 6 and 24 months after completion of maintenance therapy.~Grade 3-4 CHF were identified through a clinical review of all study collected investigator verbatim and the Medical Dictionary for Regulatory Activities (MedDRA). The preferred terms (PT) cardiac failure congestive, cardiomyopathy, and ejection fraction decreased were associated with CHF." (NCT00365365)
Timeframe: from the first dose of study medication up to the end of follow-up (up to 3 yrs)

Interventionparticipants (Number)
Stratum 1 (AC->T + Bevacizumab)1
Stratum 2 (TAC + Bevacizumab)3
Stratum 3 (TCH + Bevacizumab).)1

[back to top]

Cytotoxic T-cell Response to Vaccine Therapy Comprising 5 Synthetic Ovarian Cancer-associated Peptides, as Assessed Using Peripheral Blood During Course 1

T cell response by interferon-gamma ELIspot assay, after 1 in vitro stimulation (NCT00373217)
Timeframe: through week 3

InterventionParticipants (Count of Participants)
Group 1: Adjuvant1
Group 2: Neoadjuvant1

[back to top]

Cytotoxic T-cell Response to Vaccine Therapy Comprising Synthetic Ovarian Cancer-associated Peptides, as Assessed Using Peripheral Blood During Chemotherapy and During Course 2

T cell response to one or more peptides in peripheral blood by IFN-gamma ELIspot assay during chemotherapy and/or during 2nd course of vaccines. (NCT00373217)
Timeframe: weeks 4-28 for group 1, week 4-16 for group 2

InterventionParticipants (Count of Participants)
Group 1: Adjuvant2
Group 2: Neoadjuvant1

[back to top]

Overall Survival Rate

(NCT00383266)
Timeframe: 1 year

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin22.2

[back to top]

Overall Survival (OS)

OS is defined as the time from initiation of treatment to the date of any reason death while those living subjects will be censored at the last assessment date. (NCT00383266)
Timeframe: Until patient's death (median follow-up 293 days -- range (63-632 days))

Interventionmonths (Median)
Pemetrexed + Carboplatin9.6

[back to top]

Overall Response Rate (ORR)

"Overall response rate = complete response (CR) + partial response (PR) using RECIST.~CR=disappearance of all target lesions and disappearance of all non-target lesions and normalization of tumor marker level~PR=at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD" (NCT00383266)
Timeframe: Until patient progresses or dies (median follow-up 293 days -- range (63-632 days)

Interventionpercentage of participants (Number)
Complete responsePartial response
Pemetrexed + Carboplatin033

[back to top]

Time to Disease Progression

-Progressive disease=at least a 20% increase in the sum of the LD of the target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions (NCT00383266)
Timeframe: Until patient progresses (median follow-up 293 days -- range (63-632 days)

Interventionmonths (Median)
Pemetrexed + Carboplatin3.6

[back to top]

Toxicities

(NCT00383266)
Timeframe: 30 days following completion of treatment (maximum number of cycles = 6)

Interventionparticipants (Number)
Cardiac ischemia/infarctionPancreatitisTumor painChest/thorax painHemoglobinChest painDry eye syndromeAbdominal painConstipationDiarrheaDysphagiaHiccoughsMucositisNauseaOral cavity painStomatitisVomitingChillsEdemaFatigueFeverSweatingColitis (c. difficile)Infection without neutropeniaALTASTAlkaline phosphtaseLeukocytes (WBC)Low CO2LymphopeniaNeutrophilsPlateletsWeight lossAnorexiaDehydrationHypercalcemiaHyperglycemiaHyperkalemiaHypernatremiaHypoalbuminemiaHypocalcemiaHypoglycemiaHypokalemiaHyponatremiaLipaseBack painHerniaLimb painDizzinessHeadacheNeuropathy - motorNeuropathy - sensoryInsomniaMood alteration - anxietyCreatinineCreatinine clearanceAllergic rhintisCoughDyspneaHemorrhage - noseAlopeciaDry skinOther: skinPuritisRashSkin breakdown/decubitous ulcerHot flash
Pemetrexed + Carboplatin1111811233112611421515114223262112113333111111113315421124311211111

[back to top]

Overall Survival Rate

(NCT00383266)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin0

[back to top]

Median Survival of Patients Treated With This Regimen

The length of time from the start of treatment that half of the patients in a group of patients diagnosed with the disease are still alive. (NCT00387660)
Timeframe: Up to 36 months

Interventionmonths (Median)
Arm A10
Arm B10

[back to top]

Number of Participants With Toxicity

All adverse events were graded according to the National Cancer InstituteCommon Toxicity Criteria, version 2.0. All 80 patients were assessable for toxicity at least for the first cycle. (NCT00387660)
Timeframe: Up to 36 months

InterventionParticipants (Count of Participants)
Arm A40
Arm B40

[back to top]

Overall Response Rate

Per Response Evaluation Criteria In Solid Tumors Criteria for target lesions and assessed by radiographic techniques. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00387660)
Timeframe: Up to 36 months

Interventionpercentage of participants (Number)
Arm A65
Arm B50

[back to top]

Toxicity of Paclitaxel/Carboplatin vs. Paclitaxel/Carboplatin/Sorafenib

Number of patients experiencing treatment-related adverse events (NCT00390611)
Timeframe: 18 months

,
Interventionparticipants (Number)
NeutropeniaAnemiaThrombocytopeniaFebrile neutropeniaNausea/vomitingPeripheral neuropathyFatigueSkin rashDiarrheaPain-muscleHypersensitivity reaction (paclitaxel)MucositisConstipationPain-jointAnorexiaHand-foot syndromeAbdominal painWeaknessHypertensionDizzinessFever (no neutropenia)DehydrationDyspneaHeadacheEdemaHyponatremiaPruritus
Paclitaxel/Carboplatin333025137283238141714118056265453201
Paclitaxel/Carboplatin/Sorafenib282926333312941221261679916971066535343

[back to top]

2-year Progression-free Survival

The proportion of patients with progression-free survival at 2 years. Progression-free survival is measured from Day 1 of study drug administration to disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death on study. Progression is defined in RECIST v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT00390611)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Paclitaxel/Carboplatin/Sorafenib40
Paclitaxel/Carboplatin40

[back to top]

Overall Response Rate (ORR)

Number of patients with either complete response (CR) or partial response (PR) as defined in Response Evaluation Criteria in Solid Tumors (for patients with measurable disease) or determined by CA-125 levels (for patients without measurable disease). Complete Response: Disappearance of all target lesions, disappearance of all non-target lesions, and normalization of CA-125 for at least 4 weeks. In patients who have only elevated CA-125, the CA-125 must normalize (< 23U/mL) for more than 4 weeks. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters. For patients with elevated CA-125 only, partial response will be defined as a > 50% decrease in the serum CA-125 level. (NCT00390611)
Timeframe: 18 months

Interventionparticipants (Number)
Paclitaxel/Carboplatin/Sorafenib29
Paclitaxel/Carboplatin31

[back to top]

Overall Survival (OS)

Overall survival was measured from the date of study entry until the date of death (NCT00390611)
Timeframe: 18 months

Interventionmonths (Median)
Paclitaxel/Carboplatin/Sorafenib36.5
Paclitaxel/CarboplatinNA

[back to top]

PK: AUC0-∞ for Paclitaxel With and Without Enzastaurin for Part 1 of Study

(NCT00391118)
Timeframe: Cycle 1 Day 1 (pac) and Cycle 2 Day 1 (pac + enz); pac at 1, 2, 3h (immediately after stopping infusion), 3.25, 3.5, 4, 5, 6, 8, 24, and 30h after start of infusion

Interventionng*h/mL (Geometric Mean)
Cycle 1 Day 1Cycle 2 Day 1
Part 1 - Modified Regimen A1200014400

[back to top]

PK: Cmax at Steady State (Cmax,ss) for Part 1 of Study

Cmax,ss for enzastaurin, its metabolite LSN326020 (LY326020) and total analytes are reported. (NCT00391118)
Timeframe: Cycle 1 Day 21 (enz) and Cycle 2 Day 1 (carb + pac + enz) at pre-dose, 2, 4, 6, 8 and 24h after the enz dose

Interventionnmol/L (Geometric Mean)
Enzastaurin Cycle 1 Day 21Enzastaurin Cycle 2 Day 1LSN326020 Cycle 1 Day 21LSN326020 Cycle 2 Day1Total Analyte Cycle 1 Day 21Total Analyte Cycle 2 Day 1
Part 1 - Modified Regimen A123093589081421901640

[back to top]

Part 2: Translational Research: PFS Based on Protein Expression (PE) (To Assess Biological Markers in Tumors That Could Indicate Who Could Benefit From Enzastaurin Treatment)

PE measured using Immunohistochemistry (IHC) assay, scored 0 (negative, no staining) to 3+ (brightest staining). IHC H-scores for protein biomarkers (PKCβ2, PTEN, pCREB, pGSK3b, pS6) calculated as: [1*(percentage of cells stained [PCS] as 1+)]+[2*(PCS as 2+)]+[3*(PCS as 3+)]. High PE: ≥marker threshold value and Low PE: NCT00391118)
Timeframe: Randomization up to date of PD or death (up to 28.6 months)

,
Interventionmonths (Median)
PKCβ2 Cytoplasm High Expression (H≥115)PKCβ2 Cytoplasm Low Expression (H<115)PTEN Cytoplasm High Expression (H≥50)PTEN Cytoplasm Low Expression (H<50)PTEN Membrane High Expression (H≥15)PTEN Membrane Low Expression (H<15)PTEN Nucleus High Expression (H≥12)PTEN Nucleus Low Expression (H<12)pCREB Nucleus High Expression (H≥217)pCREB Nucleus Low Expression (H<217)pGSK3b Cytoplasm High Expression (H≥160)pGSK3b Cytoplasm Low Expression (H<160)pS6 Cytoplasm High Expression (H≥105)pS6 Cytoplasm Low Expression (H<105)
Part 2 - Regimen A18.919.118.9NA18.419.1NA18.419.614.0NA14.019.611.5
Part 2 - Regimen B10.418.218.210.4NA14.716.816.913.218.214.517.418.017.4

[back to top]

Number of Participants With Serious Adverse Events (SAEs), Other Non-Serious Adverse Events (AEs) and the Number of Participants Who Died (To Compare the Safety of the 2 Treatments)

Clinically significant events were defined as SAEs and other non-serious AEs regardless of causality. A summary of SAEs and other non-serious AEs regardless of causality is located in the Reported Adverse Events module. The number of participants SAEs, other non-serious AEs, and those who died due to PD are included. (NCT00391118)
Timeframe: Randomization up to 28.6 months

,,
InterventionParticipants (Count of Participants)
SAEsNon-Serious AEsDied
Part 1 - Modified Regimen A7110
Part 2 - Regimen A26603
Part 2 - Regimen B20560

[back to top]

PK: Cmax for Paclitaxel With and Without Enzastaurin for Part 1 of Study

(NCT00391118)
Timeframe: Cycle 1 Day 1 (pac) and Cycle 2 Day 1 (pac + enz); pac 1, 2, 3h (immediately after stopping infusion), 3.25, 3.5, 4, 5, 6, 8, 24, and 30h after start of infusion

Interventionnanograms/milliliter (ng/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 2 Day 1
Part 1 - Modified Regimen A35803670

[back to top]

Part 2: Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Overall Response Rate (ORR)]

ORR was the percentage of participants with a CR or PR using RECIST v1.0 and CA-125 GCIG criteria. RECIST v1.0: CR was defined as the disappearance of all tumors. PR was defined ≥30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD or complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesions and appearance of no new lesions. GCIG: CA-125 serum ≥2 times above ULN for those in normal range or nadir for participants who never achieved normal range. ORR calculated as: (CR + PR) / (total number of participants qualified for tumor response analysis per arm) * 100. (NCT00391118)
Timeframe: Randomization to PD or death from any cause (up to 28.6 months)

Interventionpercentage of participants (Number)
Part 2 - Regimen A42.9
Part 2 - Regimen B38.9

[back to top]

Part 2: Percentage of Participants With PFS at 2 Years

PFS was defined as time from date of randomization to first date of determined PD or death from any cause. PD defined using RECIST v1.0 and GCIG criteria. RECIST v1.0: as ≥20% increase in sum of LD of target lesions taking as reference the smallest sum LD recorded since treatment started or appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. GCIG: CA-125 serum ≥2 times ULN for those in normal range or nadir (the lowest value of blood counts after chemotherapy) for participants who never achieved normal range. Participants not known to have died and did not have PD were censored at last progression-free assessment. Those who received subsequent systemic anticancer therapy (after study drug discontinued) prior to determined PD or death, were censored at date of last progression-free disease assessment prior to post-discontinuation chemotherapy. (NCT00391118)
Timeframe: Randomization to measured PD evaluated at 2 years

Interventionpercentage of participants (Number)
Part 2 - Regimen A35.2
Part 2 - Regimen B28.2

[back to top]

Part 2: Progression-Free Survival (PFS)

PFS was defined as time from date of randomization to first date of determined progressive disease (PD) or death from any cause. PD defined using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) and Gynecological Cancer Intergroup (GCIG) criteria. RECIST: ≥20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since treatment started or appearance of ≥ 1new lesions and/or unequivocal progression of existing non-target lesions. GCIG: Cancer Antigen-125 (CA-125) serum ≥2 times upper limit of normal (ULN) for those in normal range or nadir for participants who never achieved normal range. Participants not known to have died and did not have PD were censored at last progression-free assessment. Those who received subsequent systemic anticancer therapy (after study drug discontinued) prior to determined PD or death, were censored at date of last progression-free disease assessment prior to post-discontinuation chemotherapy. (NCT00391118)
Timeframe: Randomization up to date of PD or death (up to 28.6 months)

Interventionmonths (Median)
Part 2 - Regimen A18.9
Part 2 - Regimen B15.2

[back to top]

Part 2: Percentage of Participants With CR or PR or Stable Disease (SD) (Rate of Response)

Rate of response was defined using RECIST v1.0 and CA-125 GCIG criteria. RECIST v1.0: CR was defined as the disappearance of all target lesions. PR was defined ≥30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD or complete disappearance of target lesions, with persistence (but not worsening) of ≥1 nontarget lesions and appearance of no new lesions. SD was defined as small changes that did not meet the above criteria. PD was defined as having a ≥20% increase in the sum of the LD of target lesions. GCIG: CA-125 serum ≥2 times above ULN for those in normal range or nadir for participants who never achieved normal range. Rate of response calculated as: (CR + PR + SD)/(total number of participants qualified for tumor response analysis per arm) *100. (NCT00391118)
Timeframe: Randomization to PD or death from any cause (up to 28.6 months)

,
Interventionpercentage of participants (Number)
CRPRSD
Part 2 - Regimen A7.135.742.9
Part 2 - Regimen B22.216.750.0

[back to top]

Pharmacokinetics (PK): Maximum Concentration (Cmax) for Carboplatin With and Without Enzastaurin for Part 1 of Study

(NCT00391118)
Timeframe: Cycle 1 Day 1 (carb) and Cycle 2 Day 1 (carb + enz); carb 0.25 hours (h) (prior to infusion), 0.5, 1, 2, 3, 5, and 21h after start of infusion

Interventionmicrograms/milliliter (µg/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 2 Day 1
Part 1 - Modified Regimen A11.110.8

[back to top]

PK: AUC From Time 0 to Infinity (AUC0-∞) for Carboplatin With and Without Enzastaurin for Part 1 of Study

(NCT00391118)
Timeframe: Cycle 1 Day 1 (carb) and Cycle 2 Day 1 (carb + enz); carb at 0.25h (prior to infusion), 0.5, 1, 2, 3, 5, and 21h after start of infusion

Interventionmilligrams*minute/milliliter (mg*min/mL (Geometric Mean)
Cycle 1 Day 1Cycle 2 Day 1
Part 1 - Modified Regimen A3.323.80

[back to top]

PK: AUC During the Dosing Interval at Steady State (AUCτ,ss) for Part 2 of Study

AUCτ,ss for enzastaurin, its metabolite LSN326020 (LY326020), and total analytes are reported. (NCT00391118)
Timeframe: Cycle 2 Day 1 (carb + pac + enz) at pre-dose, 2, 4, 6, 8 and 24h after the enz dose

Interventionnmol*h/L (Geometric Mean)
EnzastaurinLSN326020Total Analyte
Part 2 - Regimen A4710055600106000

[back to top]

Tumor Response to Radiation Therapy for Patients With Medulloblastoma

Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses. (NCT00392327)
Timeframe: 12 weeks after treatment initiation

Interventionpercentage of patients (Number)
Regimen A (Medulloblastoma Patients)75.9
Regimen B (Medulloblastoma Patients)78.8
Regimen C (Medulloblastoma Patients)72.9
Regimen D (Medulloblastoma Patients)81.8

[back to top]

The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for SPNET Patients

Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. (NCT00392327)
Timeframe: 6 - 12 months post diagnosis

InterventionScore on a scale (Mean)
Regimen A (SPNET Patients)84.6
Regimen B (SPNET Patients)80.3
Regimen C (SPNET Patients)99.3
Regimen D (SPNET Patients)90.6

[back to top]

The Estimated Full-scale IQ (FSIQ) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients

Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 9+/-3 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. (NCT00392327)
Timeframe: 6 - 12 months post diagnosis

InterventionScore on a scale (Mean)
Regimen A (Medulloblastoma Patients)96.6
Regimen B (Medulloblastoma Patients)89.1
Regimen C (Medulloblastoma Patients)83.5
Regimen D (Medulloblastoma Patients)94.8

[back to top]

The Estimated Full-scale IQ (FSIQ) at 60+/-12 Months Post Diagnosis for SPNET Patients

Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 60+/-12 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. (NCT00392327)
Timeframe: 48 - 72 months post diagnosis

Interventionscore on a scale (Mean)
Regimen A (SPNET Patients)94.8
Regimen B (SPNET Patients)48.0
Regimen C (SPNET Patients)87.0
Regimen D (SPNET Patients)79.7

[back to top]

Percent Probability of Overall Survival (OS) for Patients With Medulloblastoma

The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined. (NCT00392327)
Timeframe: Up to 5 years

InterventionPercent Probability (Number)
Regimen A (Medulloblastoma Patients)66.0
Regimen B (Medulloblastoma Patients)75.9
Regimen C (Medulloblastoma Patients)69.9
Regimen D (Medulloblastoma Patients)81.6

[back to top]

Percent Probability of Event-free Survival (EFS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)

The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. (NCT00392327)
Timeframe: Up to 5 years

InterventionPercent Probability (Number)
Regimen A (SPNET Patients)52.2
Regimen B (SPNET Patients)52.6
Regimen C (SPNET Patients)19
Regimen D (SPNET Patients)63

[back to top]

Percent Probability of Event-free Survival (EFS) for Patients With Medulloblastoma

The Kaplan-Meier method will be used to estimate 5-year EFS, defined as the time from study enrollment to disease progression or recurrence, second malignant neoplasm, or death from any cause, or to date of last contact. Estimates are reported with 95% confidence intervals. Data below represents all molecular subgroups combined. (NCT00392327)
Timeframe: Up to 5 years

InterventionPercent Probability (Number)
Regimen A (Medulloblastoma Patients)57.5
Regimen B (Medulloblastoma Patients)65.3
Regimen C (Medulloblastoma Patients)60.3
Regimen D (Medulloblastoma Patients)70.9

[back to top]

Percent Probability of Overall Survival (OS) for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)

The Kaplan-Meier method will be used to estimate 5-year OS, defined as the time from study enrollment to death from any cause, or to date of last contact. (NCT00392327)
Timeframe: Up to 5 years

InterventionPercent Probability (Number)
Regimen A (SPNET Patients)60.9
Regimen B (SPNET Patients)57.9
Regimen C (SPNET Patients)35.3
Regimen D (SPNET Patients)77.0

[back to top]

Tumor Response to Radiation Therapy for Patients With Supratentorial Primitive Neuroectodermal Tumor (SPNET)

Percentages of patients with responses after radiation therapy (induction therapy) are reported with 95% confidence intervals. Complete and partial responses were considered responses. SPNET is no longer recognized by WHO (World Health Organization) as a disease entity. Additional trial information can be found under PubMed® # 30332335. (NCT00392327)
Timeframe: 12 weeks after treatment initiation

Interventionpercentage of patients (Number)
Regimen A (SPNET Patients)69.9
Regimen B (SPNET Patients)83.3
Regimen C (SPNET Patients)66.7
Regimen D (SPNET Patients)73.7

[back to top]

Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 30+/-6 Months Post Diagnosis for SPNET Patients

Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. (NCT00392327)
Timeframe: 24 - 36 months post diagnosis

InterventionT-Score (Mean)
Regimen A (SPNET Patients)53.5
Regimen B (SPNET Patients)75.5
Regimen C (SPNET Patients)64.5
Regimen D (SPNET Patients)53.5

[back to top]

Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 60+/-12 Months Post Diagnosis for SPNET Patients

Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. (NCT00392327)
Timeframe: 48 - 72 months post diagnosis

InterventionT-Score (Mean)
Regimen A (SPNET Patients)56.0
Regimen B (SPNET Patients)64.0
Regimen C (SPNET Patients)71.5
Regimen D (SPNET Patients)53.7

[back to top]

Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for Medulloblastoma Patients

Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. (NCT00392327)
Timeframe: 6 - 12 months post diagnosis

InterventionT-Score (Mean)
Regimen A (Medulloblastoma Patients)50.9
Regimen B (Medulloblastoma Patients)50.2
Regimen C (Medulloblastoma Patients)50.8
Regimen D (Medulloblastoma Patients)47.5

[back to top]

Metacognition Index (MI) on the Behavior Rating Inventory of Executive Function (BRIEF) at 9+/-3 Months Post Diagnosis for SPNET Patients

Metacognition index (MI) was measured by BRIEF test. Assessments within the time window, from eligible and evaluable patients are reported. If the patient had disease progression, only the assessments before progression date were reported. The MI is a standard T- score, and it ranges from 0 to 100. The higher score reported suggests a higher level of dysfunction. Mean and standard deviation of MI were calculated and reported. (NCT00392327)
Timeframe: 6 - 12 months post diagnosis

InterventionT-Score (Mean)
Regimen A (SPNET Patients)53.8
Regimen B (SPNET Patients)66.7
Regimen C (SPNET Patients)46.1
Regimen D (SPNET Patients)64.3

[back to top]

The Estimated Full-scale IQ (FSIQ) at 30+/-6 Months Post Diagnosis for SPNET Patients

Post-treatment neurocognitive function was assessed. Full-scale IQ (FSIQ) is a representative measurement for neurocognitive function. FSIQ was measured by IQ tests. Assessments within the time window, from eligible and evaluable patients are reported. The time window is 30+/-6 months post diagnosis, only the assessments before progression date were reported. The Range of FSIQ is 50-150. A higher FSIQ is better. Mean and standard deviation of FSIQ were calculated and reported. (NCT00392327)
Timeframe: 24 - 36 months post diagnosis

InterventionScore on a scale (Mean)
Regimen A (SPNET Patients)83.3
Regimen B (SPNET Patients)57.5
Regimen C (SPNET Patients)83.7
Regimen D (SPNET Patients)88.5

[back to top]

Progression-Free Survival

Progression-free survival (PFS) was defined as the interval from the date of first treatment until the date of disease progression or death, whichever occurred first. Patients who did not progress were censored at the date of their last tumor assessment. (NCT00393068)
Timeframe: 36 months

Interventionmonths (Median)
Treatment28.58

[back to top]

Pathologic Complete Response (pCR) Rate

pCR was defined as no residual viable cancer found at the primary site or regional lymph nodes upon pathologic review of the surgical specimen for patients who went to surgical resection. (NCT00393068)
Timeframe: 18 months

InterventionParticipants (Count of Participants)
Treatment18

[back to top]

Overall Survival

Overall Survival (OS) is defined as the time interval from the start of treatment until death. Patients who remained alive were censored at the date of their last tumor assessment. (NCT00393068)
Timeframe: 32 months

Interventionmonths (Median)
Treatment30.16

[back to top]

Time to Best Response

Time to best response is defined as the time from the start of treatment until first documented evidence of tumor response (30% decrease or complete disappearance of tumor). For subjects who do not show a tumor response, the time will be censored at the time of last contact. (NCT00400803)
Timeframe: From Enrollment to First Tumor Response

InterventionDays (Median)
Intent To Treat - Lung Cancer Patients72

[back to top]

Overall Survival Time

Overall survival is defined as the time from the start of treatment until death due to whatever cause. For subjects alive at study completion, time to death will be censored at the time of last contact. (NCT00400803)
Timeframe: Baseline to Death

InterventionMonths (Mean)
Intent To Treat - Lung Cancer Patients14.3

[back to top]

Time to Progression

Time to progression (progression free survival)is defined as the time from the start of treatment until first documented sign of disease progression or death due to any cause. For subjects who do not progress, time to progression will be censored at the time of last tumor assessment. (NCT00400803)
Timeframe: From Enrollment Through 2 Years

InterventionMonths (Mean)
Intent To Treat - Lung Cancer Patients3.1

[back to top]

Best Overall Response by Cycle

Number of patients and their best response recorded from the state of treatment until disease progression. Response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST): Complete Response-disappearance of all target lesions; Partial Response=30% decrease in sum of longest diameter of target lesions; Progressive Disease=20% increase in sum of longest diameter of target lesions; Stable Disease=small changes that did not meet above criteria. (NCT00400803)
Timeframe: After Cycle 4, Cycle 6 and Cycle 7 of Therapy

,,,
InterventionParticipants (Number)
Cycle 1Cycle 2Cycle 3Cycle 4Cycle 5Cycle 6Cycle 7
Intent To Treat - Lung Cancer Patients11324024
Partial Response00015022
Progressive Disease1113000
Stable Disease0026002

[back to top]

Duration of Response

For subjects who show a response, duration of response is defined to be the time from first documented evidence of response(30% decrease or complete disappearance of tumor) until the first documented sign of disease progression or death due to any cause. For subjects who do not progress or die, duration of response will be censored at the time of last tumor assessment. (NCT00400803)
Timeframe: From Enrollment through Date of First Documented Disease Progression or Date of Death From Any Cause, Whichever Came First, Up to 100 Months

InterventionDays (Median)
Intent To Treat - Lung Cancer Patients105

[back to top]

Time to Treatment Failure (TTF)

Defined as time from randomization to the first date of disease progression, death due to any cause, or early discontinuation of treatment (any reason), whichever occurred first (NCT00402051)
Timeframe: Randomization to stopping of treatment, progression, death or initiation of further chemotherapy, whichever occurs first (up to 1 year)

Interventionmonths (Median)
Pemetrexed + Cisplatin3.0
Pemetrexed + Carboplatin3.4

[back to top]

Pharmacology Toxicities

Number of patients experiencing Grade 3 or 4 hematologic and non-hematologic adverse events (AEs) possibly related to study drug or protocol procedures in this study (a subset of those listed in the AE Module). AEs were graded using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) for defining and grading specific adverse events. A grading (severity) scale is provided for each adverse event term. Grades range from 0 (none) to 5 (death). Grade 3 AEs are severe and undesirable; Grade 4 AEs are life-threatening or disabling. (NCT00402051)
Timeframe: Every 21-day cycle for up to 6 cycles

,
Interventionparticipants (Number)
Any Grade 3/4 ToxicityGrade 3/4 LeucopeniaGrade 3/4 NeutropeniaGrade 3/4 AnemiaGrade 3/4 ThrombocytopeniaGrade 3/4 NauseaGrade 3/4 VomitingGrade 3/4 FatigueGrade 3/4 AnorexiaGrade 3/4 Urinary Tract Infection
Pemetrexed + Carboplatin36121771151222
Pemetrexed + Cisplatin298115232210

[back to top]

Number of Participants With Tumor Response (as Basis for Response Rate)

"Best overall response was evaluated using RECIST Criteria which define when cancer patients improve (respond), stay the same (stabilize), or worsen (progression) during treatment. CR: complete response, disappearance of all target lesions; PR: partial response, 30% decrease in sum of the longest diameter of target lesions; PD: progressive disease, 20% increase in sum of the longest diameter of target lesions; SD: stable disease, small changes not meeting above criteria. Response Rate: number of participants with response(CR+PR)per total population, multiplied by 100 to give a percentage." (NCT00402051)
Timeframe: Every 6 weeks for 6 months during the treatment period, and every 3 months during the follow-up period, until disease progression

,
Interventionparticipants (Number)
Partial ResponseStable DiseaseDisease ProgressionUnknown/Not Done
Pemetrexed + Carboplatin1332155
Pemetrexed + Cisplatin213176

[back to top]

Percentage of Participants Surviving Progression-Free at 6 Months (Progression Free Survival [PFS] Rate)

For this study, we used the exponential distribution (assumption done for the calculation of the sample size) to estimate the PFS rate. The PFS rate (%) and the 95% confidence intervals were calculated based on the following formula: exp(-6 λ) ± 1.96 * exp(-6 λ) * (-6 λ)/√r. Where λ was calculated based on the Maximum-Likelihood estimator for ln(λ) as given by (Collett 2003): ln(λ) = ln[ r / ∑ti ] with r = number of patients with events up to 6 months, ti = survival time of patient i (i=1,…,n), event or censored up to 6 months, and n= total number of patients per treatment group. (NCT00402051)
Timeframe: Randomization to Month 6

Interventionpercentage (Number)
Pemetrexed + Cisplatin52.8
Pemetrexed + Carboplatin39.3

[back to top]

Overall Survival

Defined as the time from randomization to the date of death from any cause. (NCT00402051)
Timeframe: Randomization to date of death from any cause (up to 1 year)

Interventionmonths (Median)
Pemetrexed + Cisplatin11.7
Pemetrexed + Carboplatin8.9

[back to top]

Number of Treatment Cycles Administered

Number of treatment cycles administered is defined to be the number of treatment cycles administered until the patient is removed from treatment due to progression, toxicity, or refusal. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00404235)
Timeframe: Up to 2 years

Interventioncycles (Median)
Cohort 1 (Prior Chemotherapy, PT)4
Cohort 2 (Chemotherapy Naive, CN)4

[back to top]

Time to Disease Progression

Time-to-disease progression (TTP) is defined as the time from registration to documentation of disease progression. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time-to-progression will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00404235)
Timeframe: Up to 2 years

Interventionmonths (Median)
Cohort 1 (Prior Chemotherapy, PT)4.1
Cohort 2 (Chemotherapy Naive, CN)4.5

[back to top]

Tumor Response Rate, as Measured by RECIST Criteria

The RECIST criteria will be used for response assessments. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. A confirmed tumor response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart. The tumor response rate is defined as the total number of eligible patients who achieved a complete or partial response according to the RECIST criteria divided by the total number of eligible patients enrolled on study. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be evaluable for response. (NCT00404235)
Timeframe: Up to 2 years

Interventionpercentage of participants (Number)
Cohort 1 (Prior Chemotherapy, PT)8.8
Cohort 2 (Chemotherapy Naive, CN)25.6

[back to top]

Duration of Response

Duration of response is defined for all eligible patients who have achieved an objective response as the date at which the patient's objective status is first noted to be either a CR or PR to the date progression is documented. (NCT00404235)
Timeframe: Up to 3 years

Interventionmonths (Median)
Cohort 1 (Prior Chemotherapy, PT)3.5
Cohort 2 (Chemotherapy Naive, CN)12.1

[back to top]

Survival Time

Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00404235)
Timeframe: Up to 2 years

Interventionmonths (Median)
Cohort 1 (Prior Chemotherapy, PT)10.9
Cohort 2 (Chemotherapy Naive, CN)11.1

[back to top]

Progression Free Survival Rate at 9 Months

This Outcome is measuring the number of particpants who have survived. (NCT00408070)
Timeframe: 9 months

Interventionparticipants (Number)
Bevacizumab Plus Carboplatin and Paclitaxel4

[back to top]

Platelet Count on Day 22

Platelet count on Day 22 of the first on study chemotherapy treatment cycle (planned Day 1 of next cycle) by treatment group (NCT00413283)
Timeframe: Day 22

Intervention10^9/L (Mean)
Placebo281.2
Romiplostim 250 µg222.6
Romiplostim 500 µg412.8
Romiplostim 750 µg336.0

[back to top]

Duration of Grade 3 or 4 Thrombocytopenia

The duration of grade 3 or 4 thrombocytopenia (defined as platelet count <50 x 10^9/L) experienced during the first on study chemotherapy cycle by treatment group. (NCT00413283)
Timeframe: 3 weeks

Interventiondays (Mean)
Placebo2.1
Romiplostim 250 µg3.6
Romiplostim 500 µg2.6
Romiplostim 750 µg2.1

[back to top]

Gemcitabine Dose Reduction on Day 8 of the First Chemotherapy Cycle

Number of participants who required a gemcitabine dose reduction on Day 8 of the first on study chemotherapy cycle. (NCT00413283)
Timeframe: 8 days

InterventionParticipants (Number)
Placebo2
Romiplostim 250 µg4
Romiplostim 500 µg4
Romiplostim 750 µg5

[back to top]

Number of Participants With Adverse Events

This summary includes all treatment-emergent adverse events recorded from the start of investigational product on this study, or any worsening of adverse events initially experienced before initiation of this study. (NCT00413283)
Timeframe: 4 months

InterventionParticipants (Number)
Placebo12
Romiplostim 250 µg16
Romiplostim 500 µg18
Romiplostim 750 µg14

[back to top]

Number of Participants With Platelet Transfusions

Number of participants who were administered platelet transfusions during first on study treatment cycle. (NCT00413283)
Timeframe: 3 weeks

InterventionParticipants (Number)
Placebo1
Romiplostim 250 µg4
Romiplostim 500 µg1
Romiplostim 750 µg1

[back to top]

Number of Participants Experiencing Grade 3 or 4 Thrombocytopenia During the First Treatment Cycle.

The number of participants in each treatment group with grade 3 or 4 thrombocytopenia during the first on study treatment cycle. Per the Common Terminology Criteria for Adverse Events (CTCAE) v3.0, participants with a platelet count < 50 x 10^9/L, but ≥ 25 x 10^9/L are considered to have Grade 3 thrombocytopenia and participants with a platelet count < 25 x 10^9/L are considered to have Grade 4 thrombocytopenia. Additionally, participants with a platelet transfusion during the first on-study treatment cycle were classified as having Grade 3/4 thrombocytopenia. (NCT00413283)
Timeframe: 3 weeks

InterventionParticipants (Number)
Placebo5
Romiplostim 250 µg7
Romiplostim 500 µg7
Romiplostim 750 µg7

[back to top]

Overall Survival Rate at 6 Months

Overall survival (OS) at 6 months with the combination of bortezomib and carboplatin in participants who previously received 1 prior regimen for metastatic pancreatic cancer from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 6 months. Rate equals number of participants living at 6 months following treatment divided by the total number of participants. (NCT00416793)
Timeframe: up to 6 months

InterventionProportion of participants (Number)
Bortezomib + Carboplatin0

[back to top]

Overall Response Rate

Overall Response Rate measured by number of patients per the total treatment population who partially or completely responded to treatment. Participants reevaluated for response every 6 weeks. In addition to a baseline scan, confirmatory scans at 4 weeks following initial documentation of objective response. (NCT00416793)
Timeframe: from assignment of treatment until the date of first documented progression, assessed up to 17 months

InterventionParticipants (Count of Participants)
Bortezomib + Carboplatin0

[back to top]

Time to Progression

Time to progression, defined as the interval between the first dates of treatment until the first notation of disease progression. RECIST criteria (NCT00421889)
Timeframe: Throughout study

Interventiondays (Median)
Part B: Ovarian Cancer MTD195
Part C: 3-6 Hours Infusion, Solid Tumors Except Ovarian Cancer150
Part D: Bladder Cancer MTD136

[back to top]

Maximum Tolerable Dose (MTD) Belinostat, Part A,

To determine the maximum tolerated dose of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin (AUC of 5) and paclitaxel (175 mg/m2). (NCT00421889)
Timeframe: Cycle 1

Interventionmg/m2 (Number)
Part A1000

[back to top]

Duration of Response

Defined as interval from the time criteria for CR or PR are met, until the first date that recurrent or progressive disease is objectively documented. (NCT00421889)
Timeframe: Throughout study

Interventiondays (Median)
Part B: Ovarian Cancer MTDNA
Part D: Bladder Cancer MTDNA

[back to top]

Dose Limiting Toxicities (DLT), Part A

To determine the number of participants experiencing dose limiting toxicities of belinostat (PXD101) in doses up to 1000 mg/m²/day administered in combination with standard doses of carboplatin and paclitaxel or both. (NCT00421889)
Timeframe: Cycle 1

Interventionparticipants (Number)
Part A0

[back to top]

Best Overall Response (CR or PR)

Best overall responses were assessed by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Clinical tumor evaluation will take place after each cycle. Formal radiological evaluation after every 2 cycles. If a response is noted, a follow-up radiographic assessment must be performed 4 weeks (+ 1 week) after the response is noted (NCT00421889)
Timeframe: Throughout study until PD (progressive disease) or lost to follow up

Interventionparticipants (Number)
Part A: Dose Escalation 600/5/NA1
Part A: Dose Escalation 600/NA/1750
Part A: Dose Escalation 600/5/1750
Part A: Dose Escalation 800/5/1750
Part A: Dose Escalation 1000/5/1751
Part B: Ovarian Cancer MTD15
Part C: 3 Hours Infusion, Solid Tumors Except Ovarian Cancer0
Part C: 6 Hours Infusion Solid Tumors, Except Ovarian Cancer0
Part D: Bladder Cancer MTD4

[back to top]

Belinostat Mean t½

(NCT00421889)
Timeframe: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h

Interventionhours (Mean)
Belinostat 600 mg/30 Minutes1.41
Belinostat 800 mg/30 Min1.16
Belinostat 1000 mg/30 Min0.898
Belinostat 1000 mg/3-hours3.76
Belinostat 1000 mg/6-hours1.9

[back to top]

Belinostat Cmax

(NCT00421889)
Timeframe: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h

Interventionng/mL (Mean)
Belinostat 600 mg/30 Minutes18592
Belinostat 800 mg/30 Min22525
Belinostat 1000 mg/30 Min31517
Belinostat 1000 mg/3-hours8340
Belinostat 1000 mg/6-hours2873

[back to top]

Belinostat AUC (0-infinity)

(NCT00421889)
Timeframe: Cycle 1 Day 1: Cycle 1 day 1: Pre-Infusion, 0 min, 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 3 h 15 min, 3 h 30 min, 4 h, 5 h, 6 h, 6 h 15 min, 6 h 30 min, 7h, 8h, 9h, 24h

Interventionng*h/mL (Mean)
Belinostat 600 mg/30 Minutes9116
Belinostat 800 mg/30 Min11785
Belinostat 1000 mg/30 Min21057
Belinostat 1000 mg/3-hours31515
Belinostat 1000 mg/6-hours13107

[back to top]

Time to Response

Time to response (RECIST) was assessed as the interval between the first dates of treatment until the first notation of response. (NCT00421889)
Timeframe: Throughout study

Interventiondays (Median)
Part B: Ovarian Cancer MTDNA
Part D: Bladder Cancer MTDNA

[back to top]

Response

"Response assessed at the completion of therapy (after four to five cycles of chemotherapy and after surgery if necessary)~Complete Response (CR): A complete response is defined as one of the following:~Complete disappearance of all clinical and radiographic and biochemical (normal AFP and HCG) evidence of disease for a minimum of 4 weeks (CR to chemotherapy).~Complete disappearance of all biochemical evidence of disease with resection of residual radiographic masses that prove to be negative for residual GCT; this includes both mature teratoma and necrotic debris (CR to chemotherapy) for a minimum of 4 weeks.~Complete disappearance of all biochemical evidence of disease with complete surgical excision of all residual radiographic masses that, if pathologically positive for residual malignant GCT, show margins to microscopically free of disease (CR to chemotherapy + surgery). Patients must be free of disease for a minimum of 4 weeks." (NCT00423852)
Timeframe: 2 year

Interventionparticipants (Number)
Complete Response (CR)Incomplete Response (IR)Partial Response (PR)
Chemotherapy With Stem Cell Support1265

[back to top]

Maximum Tolerated Dose of Ifosfamide

(NCT00423852)
Timeframe: 4 years

Interventionmg/m2 (Number)
Chemotherapy With Stem Cell Support9990

[back to top]

Number of Subjects Who Require Dose Delay/Reduction in Dose of Bortezomibin the First Cycle

Dose limiting toxicity at Level 1,2 and 3: Number of subjects who required dose delay/reduction in dose of bortezomib in the first cycle of treatment. DLT defined by any of the following during first cycle: (1) GR4 neutropenia or thrombocytopenia, (2) Greater than GR3 non-hematological toxicity except alopecia or inadequately treated nausea or vomiting or (3) neurosensory toxicity of GR2 with pain or any neurotoxicity greater than GR2. (NCT00424840)
Timeframe: up to 21 days for each dosing cycle

Interventionparticipants (Number)
Phase I: Dose Level 10
Phase 1 Dose Level II:0
Phase I Dose Level III0

[back to top]

Median Progression Free Survival (PFS)

Kaplan-Meier estimate of the median time from randomization to death from any cause or first observed disease progression. PFS time measured in months. (NCT00429182)
Timeframe: Overall study (baseline to disease progression)

Interventionmonths (Median)
High-dose Chemotherapy10.6

[back to top]

Number of Participants With Reduction in CTCs Following High-dose Chemotherapy With Purged Autologous Stem Cell Products

Number of circulating tumor cells (CTCs) measured at one month post autologous hematopoietic stem cell transplantation (AHST), considered both as longitudinal values and compared to the baseline number of CTCs. (NCT00429182)
Timeframe: Baseline to 1 month post AHST

Interventionparticipants (Number)
High-dose Chemotherapy9

[back to top]

Engraftment of Neutrophils

Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater. (NCT00432094)
Timeframe: Day 42

InterventionParticipants (Count of Participants)
2 Transplants13
1 Transplant9

[back to top]

Disease-free Survival (DFS)

The number of patients who survive without any signs of symptions of that cancer or any other cancer. (NCT00432094)
Timeframe: 1 Year

Interventionpercentage of participants (Mean)
2 Transplants64
1 Transplant44

[back to top]

Overall Survival (OS)

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. (NCT00432094)
Timeframe: 1 Year

Interventionpercentage of participants (Mean)
2 Transplants86
1 Transplant56

[back to top]

Numbers of Patients Unable to Mobilize Peripheral Blood Stem Cells

Number of patients unable to achieve adequate stem cell mobilization, need to undergo one or tandem transplantation. Stem cell mobilization = A process in which certain drugs are used to cause the movement of stem cells from the bone marrow into the blood. The stem cells can be collected and stored. They may be used later to replace the bone marrow during a stem cell transplant. (NCT00432094)
Timeframe: Pre-Transplant

InterventionParticipants (Count of Participants)
2 Transplants0
1 Transplant0

[back to top]

Engraftment of Platelets

Platelet engraftment is defined as 20,000/mm^3 (20 x 10^9/L) for 3 consecutive days unsupported by a platelet transfusion. (NCT00432094)
Timeframe: Day 100

Interventionparticipants (Number)
2 Transplants13
1 Transplant8

[back to top]

Clinical Response Rate

Clinical Response Rate was measured according to the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria for target lesions before surgery: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00432172)
Timeframe: Up to week 24

InterventionParticipants (Count of Participants)
Group 1 (Luminal A) Standard Treatment31
Group 1 (Luminal A) Selective Treatment23
Group 2 (Basal) Standard Treatment32
Group 2 (Basal) Selective Treatment36

[back to top]

Incidence of Grade ≥ 3 Adverse Events

All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 (NCT00434226)
Timeframe: 60 days following the last administration of study treatment

,
Interventionparticipants (Number)
AnaemiaFebrile NutropeniaLeukopeniaNeutropeniaThrombocytopeniaCardiac ArrestLeft Ventricular DysfunctionDiarrhoeaGastrointestinal HaemorrhageAstheniaDisease ProgressionFatiguePainHepatic PainDrug HypersensitivityHypersensitivityBacterial SepsisCellulitisInfectionPneumoniaCollapse of LungAspartate Aminotransferase IncreasedBlood Alkaline Phosphatase IncreasedFibrin D Dimer IncreasedHaemoglobin DecreasedInternational Normalised Ratio IncreasedNutrophil Count DecreasedPlatelet Count DecreasedWhite Blood Cell Count DecreasedAnorexiaDehydrationHyperglycaemiaHypoalbuminaemiaHypocalcaemiaHyponatraemiaArthralgiaBack PainMuscular WeaknessMusculoskeletal PainGastric CancerLung Cancer MetastaticMetastases to Central Nervous SystemNon-Small Cell Lung CancerDizzinessConfusional StateAlbuminuriaRenal FailureChronic Obstructive Pulmonary DiseaseDyspnoeaPleural EffusionPneumonitisPulmonary EmbolismPulmonary HaemorrhageLeukocytoclastic VasculitisRashAortic AneurysmHypertension
Bevacizumab + Carboplatin/Paclitaxel0231251010113211110020000111000120121000020001011220110001
Bevacizumab + Carboplatin/Paclitaxel + Sunitinib1461871111012100001101111011421201000111101110100201201213

[back to top]

Best Response

The best overall response is the best response, per RECIST criteria, recorded from randomization until disease progression/recurrence (includes both confirmed and unconfirmed responses). Although the original primary outcome was progression-free survival, there was insufficient data available to report on that outcome. (NCT00434226)
Timeframe: From randomization until disease progression/recurrence

,
Interventionparticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseUnable to EvaluateMissing
Bevacizumab + Carboplatin/Paclitaxel099100
Bevacizumab + Carboplatin/Paclitaxel + Sunitinib01210201

[back to top]

Incidence of Adverse Events Leading to Sunitinib Discontinuation, Dose Interruption, or Dose Reduction

All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 (NCT00434226)
Timeframe: 60 days following the last administration of study treatment

Interventionparticipants (Number)
AnaemiaFebrile NutropeniaLeukopeniaNeutropeniaThrombocytopeniaLeft Ventricular DysfunctionDiarrhoeaGastrointestinal HaemorrhageNauseaStomatitisDisease ProgressionFatigueBronchitisCellulitisInfectionCollapse of LungAspartate Aminotransferase IncreasedFibrin D Dimer IncreasedInternational Normalised Ratio IncreasedNeutrophil Count DecreasedPlatelet Count DecreasedWhite Blood Cell Count DecreasedAnorexiaDehydrationHypoalbuminaemiaBack PainMuscular WeaknessMusculoskeletal PainGastric CancerMetastases to Central Nervous SystemNon-Small Cell Lung CancerDizzinessAlbuminuriaPnemothoraxDyspnoeaPulmonary EmbolismLeukocytoclastic VasculitisRashAortic AneurysmHypertension
Bevacizumab + Carboplatin/Paclitaxel + Sunitinib12411611111121111111151121111111111221113

[back to top]

Incidence of Adverse Events Leading to Bevacizumab Discontinuation or Dose Interruption

All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 (NCT00434226)
Timeframe: 60 days following the last administration of study treatment

,
Interventionparticipants (Number)
AnaemiaFebrile NutropeniaLeukopeniaNeutropeniaThrombocytopeniaCardiac ArrestDiarrhoeaGastrointestinal HaemorrhageDisease ProgressionFatigueDrug HypersensitivityHypersensitivityBronchitisInfectionCollapse of LungAspartate Aminotransferase IncreasedInternational Normalised Ratio IncreasedNeutrophil Count DecreasedPlatelet Count DecreasedDehydrationBack PainGastric CancerLung Cancer MetastaticMetastases to Central Nervous SystemMetastases to LiverNon-Small Cell Lung CancerAlbuminuriaRenal FailureHaemoptysisPleural EffusionPneumothoraxPulmonary EmbolismRashAortic AneurysmHypertensionHypotension
Bevacizumab + Carboplatin/Paclitaxel011121002111000001000010100111000021
Bevacizumab + Carboplatin/Paclitaxel + Sunitinib111330111200111110521101011000121120

[back to top]

Serious Adverse Events

All grades according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0 (NCT00434226)
Timeframe: 60 days following the last administration of study treatment

,
Interventionparticipants (Number)
AnaemiaFebrile NeutropeniaNeutropeniaThrombocytopeniaCardiac ArrestDiarrhoeaAstheniaDisease ProgressionFatiguePainHepatic PainDrug HypersensitivityCellulitisBacterial SepsisCollapse of LungPlatelet Count DecreasedHaemoglobin DecreasedNutrophil Count DecreasedDehydrationBack PainLung Cancer MetastaticGastric CancerNon-Small Cell Lung CancerConfusional StateRenal FailurePleural EffusionPneumothoraxChronic Obstructive Pulmonary DiseasePulmonary EmbolismDyspnoeaHaemoptysisPneumonitisPulmonary HaemorrhageNasal Septum PerforationAortic AneurysmHypotension
Bevacizumab + Carboplatin/Paclitaxel110010110111010011102001120201101001
Bevacizumab + Carboplatin/Paclitaxel + Sunitinib041111011000101100210110001020010110

[back to top]

Percentage of Participants With an Objective Response

"Objective response was defined as a complete or partial response according to RECIST criteria as assessed by the investigator on two consecutive assessments conducted at least 4 weeks apart.~The 95% Confidence Interval (CI) was calculated using the normal approximation to the binomial distribution." (NCT00434252)
Timeframe: Up to 102 weeks

Interventionpercentage of participants (Number)
Carboplatin+Paclitaxel+Placebo16.4
Carboplatin+Paclitaxel+Bevacizumab25.5

[back to top]

Duration of Objective Response

Duration of objective response was defined as the time from the initial objective response to documented disease progression or death, whichever occurred first, assessed by the investigator using RECIST. Progressive disease was defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started, or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Duration of response was estimated using the Kaplan-Meier method. (NCT00434252)
Timeframe: Up to 102 weeks

Interventionmonths (Median)
Carboplatin+Paclitaxel+Placebo7.7
Carboplatin+Paclitaxel+Bevacizumab6.9

[back to top]

Number of Participants With Objective Response

Objective response was assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) criteria and was inclusive of complete and partial response determined on two consecutive investigator assessments conducted ≥ 4 weeks apart. (NCT00434252)
Timeframe: Up to 102 weeks

Interventionparticipants (Number)
Carboplatin+Paclitaxel+Placebo11
Carboplatin+Paclitaxel+Bevacizumab36

[back to top]

Number of Participants With Select Adverse Events

"Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), v3.0. Select adverse events included arterial thromboembolic events (any grade), bleeding other than pulmonary or central nervous system (CNS) bleeding (Grade >= 3), CNS bleeding (any grade), febrile neutropenia (any grade), hypertension (Grade >= 3), neutropenia (Grade >= 3), pulmonary bleeding (any grade) and wound dehiscence (Grade >= 3).~*All serious adverse events are listed in the Adverse Event Reporting section." (NCT00434252)
Timeframe: Participants were monitored for AEs from initiation of treatment to 30 days after treatment termination.

,
Interventionparticipants (Number)
Arterial thromboembolic events (any grade)Bleeding other than pulmonary or CNS (Grade >=3)CNS bleeding (any grade)Febrile neutropenia (any grade)Hypertension (Grade >= 3)Neutropenia (Grade >= 3)Pulmonary bleeding (any grade)Wound dehiscence (Grade >= 3)
Carboplatin+Paclitaxel+Bevacizumab401753422
Carboplatin+Paclitaxel+Placebo140101310

[back to top]

Twenty-Four Week Landmark Stable Disease

"As assessed by the investigator using RECIST and defined as the absence of disease progression for 24 weeks from the time of randomization.~The percentage of patients who did not experience disease progression or death at 24 weeks following randomization was estimated using Kaplan-Meier methodology. If no tumor assessments were performed after the baseline visit, the patient will be censored at the date of randomization plus 1 day." (NCT00434252)
Timeframe: 24 weeks

Interventionpercentage of participants (Number)
Carboplatin+Paclitaxel+Placebo38.0
Carboplatin+Paclitaxel+Bevacizumab50.2

[back to top]

Overall Survival (OS)

Overall survival was defined as the time from randomization to death from any cause. Median OS was estimated using the Kaplan-Meier method. For patients without documentation of death, overall survival will be censored at the time of the last known contact. (NCT00434252)
Timeframe: Up to 102 weeks

Interventionmonths (Median)
Carboplatin+Paclitaxel+Placebo8.6
Carboplatin+Paclitaxel+Bevacizumab12.3

[back to top]

Progression-free Survival

Progression-free survival (PFS) was defined as the time from randomization to documented disease progression (at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions) or death on study (death from any cause occurring no later than 30 days after last dose of any study treatment), whichever occurred first, as determined by the investigator using the Response Evaluation Criteria in Solid Tumors (RECIST). Median PFS was estimated using the Kaplan-Meier method. (NCT00434252)
Timeframe: From randomization up to102 weeks. As of the clinical cut-off date (April 2009), the maximum time on treatment was 88 weeks, median time was 12.4 weeks for the Placebo arm and 16.1 weeks for the bevacizumab arm.

Interventionmonths (Median)
Carboplatin+Paclitaxel+Placebo4.2
Carboplatin+Paclitaxel+Bevacizumab5.6

[back to top]

Six-month Landmark Survival Rate

Six-month Landmark Survival Rate was defined as the percentage of participants surviving at 6 months following randomization. Overall Survival was estimated using the Kaplan-Meier method. (NCT00434252)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Carboplatin+Paclitaxel+Placebo74.6
Carboplatin+Paclitaxel+Bevacizumab78.2

[back to top]

Overall Survival

Overall survival was defined as the time from randomization to death from any cause. (NCT00434642)
Timeframe: From randomization through July 19, 2013 (up to 6 years, 3 months)

InterventionMonths (Median)
Carboplatin and Gemcitabine + Bevacizumab33.6
Carboplatin and Gemcitabine + Placebo32.9

[back to top]

Percentage of Patients With an Objective Response as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)

An objective response was the occurrence of either a partial response (PR) or complete response (CR). PR: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. CR: The disappearance of all target and non-target lesions. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks. (NCT00434642)
Timeframe: From randomization through September 17, 2010 (up to 3 years, 5 months)

InterventionPercentage of participants (Number)
Carboplatin and Gemcitabine + Bevacizumab78.5
Carboplatin and Gemcitabine + Placebo57.4

[back to top]

Duration of Objective Response (OR) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)

Duration of OR was analyzed in the subset of patients who achieved an OR. The duration of OR was defined as the time from the initial CR or PR until documented PD or death. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks. (NCT00434642)
Timeframe: From randomization through September 17, 2010 (up to 3 years, 5 months)

InterventionMonths (Median)
Carboplatin and Gemcitabine + Bevacizumab10.4
Carboplatin and Gemcitabine + Placebo7.4

[back to top]

Progression Free Survival (PFS) as Determined by the Investigator, Per Response Evaluation Criteria for Solid Tumors (RECIST)

PFS was defined as the time from randomization to disease progression (PD), as determined by the investigator, or death due to any cause. PD: At least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started; the appearance of 1 or more new lesions; and/or the unequivocal progression of existing non-target lesions. Lesions were assessed by computed tomography (CT), magnetic resonance imaging (MRI), or ultrasound every 9 weeks. (NCT00434642)
Timeframe: From randomization through September 17, 2010 (up to 3 years, 5 months)

InterventionMonths (Median)
Carboplatin and Gemcitabine + Bevacizumab12.4
Carboplatin and Gemcitabine + Placebo8.4

[back to top]

Percentage of Patients Who Had a Gastrointestinal Perforation (GIP)

A gastrointestinal perforation is a hole that develops through the entire wall of the stomach, small intestine, large bowel, or gallbladder. (NCT00434642)
Timeframe: From randomization through September 17, 2010 (up to 3 years, 5 months)

InterventionPercentage of participants (Number)
Carboplatin and Gemcitabine + Bevacizumab0
Carboplatin and Gemcitabine + Placebo0

[back to top]

Percentage of Patients Who Had at Least 1 Adverse Event

(NCT00434642)
Timeframe: From randomization through July 19, 2013 (up to 6 years, 3 months)

InterventionPercentage of participants (Number)
Carboplatin and Gemcitabine + Bevacizumab100.0
Carboplatin and Gemcitabine + Placebo100.0

[back to top]

Reponse Rate at Time of Surgery by Tissue

pathologic complete response rate at surgery (NCT00439608)
Timeframe: within 30 days of last treatment

Interventionparticipants (Number)
Treatment40

[back to top]

Number of Participants With Grade 2 and/or 3 Rash in Patients With Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus, Gastroesophageal Junction, or Stomach.

CTCAE version 3: grade 2 and 3 rash. This is reported as it was the most common toxicity. (NCT00439608)
Timeframe: baseline, then during treatment, about 5 weeks through 30 days post treatment.

Interventionparticipants (Number)
Treatment37

[back to top]

Percent of Participants With Grade 3/4 Clinical Congestive Heart Failure (CHF)

The percentage of participants with Grade 3/4 clinical CHF was calculated. Grade 3/4 CHF symptoms included cardiac failure congestive, cardiomyopathy, and left ventricular dysfunction (LVEF). Echocardiography (ECG) or multiple-gated acquisition (MUGA) scans were scheduled after Cycles 3 and 6 of chemotherapy, after every 3rd cycle of trastuzumab alone, at end of therapy and every 6 months at follow-up to measure changes in LVEF. Clinical symptoms e.g., shortness of breath, tachycardia, cough, neck vein distention, cardiomegaly, hepatomegaly were further investigated for CHF. (NCT00446030)
Timeframe: up to 2 years

InterventionPercentage of Participants (Mean)
Stratum 1: TAC + Bevacizumab4.3
Stratum 2: TCH + Bevacizumab0

[back to top]

Number of Participants With Overall Tumor Response

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): disappearance of all target lesions; Partial Response (PR) 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions; Stable Disease (SD): small changes that do not meet above criteria. Overall tumor response is the total number of CR and PRs. (NCT00453154)
Timeframe: Up to 3 years

,
Interventionparticipants (Number)
Complete ResponsePartial Response
Arm I (Combination Chemotherapy + Sunitinib Maintenance)34
Arm II (Combination Chemotherapy + Placebo Maintenance)05

[back to top]

Progression-free Survival (Phase II)

Progression free survival (PFS) was defined as the time from maintenance randomization to progression or death of any cause. Progression free and alive patients were censored at the date of last follow-up. The median PFS with 95% CI was estimated using the Kaplan Meier method. (NCT00453154)
Timeframe: Up to 3 years

Interventionmonths (Median)
Arm I (Combination Chemotherapy + Sunitinib Maintenance)3.7
Arm II (Combination Chemotherapy + Placebo Maintenance)2.1

[back to top]

Maximum Tolerated of Sunitinib Combined With Cisplatin and Etoposide (Phase I)

The maximum tolerated dose is defined at the highest sunitinib dose at which less than one third of participants develop a dose limiting toxicity (DLT). A DLT is defined as: delay of beginning cycle 2 of chemotherapy by > 7 days due to neutropenia, grade 4 hematologic toxicity lasting greater than 1 week (chemotherapy alone would be expected to cause significant grade 4 hematologic toxicity) or grade 3 or 4 nonhematologic toxicity (excluding grade 3 or 4 fatigue if the patient is found to be hypothyroid and responds to fatigue < grade 3 with thyroid replacement therapy). (NCT00453154)
Timeframe: 21 days

Interventionmg/day (Number)
Cohort 125

[back to top]

Overall Survival

Overall survival (OS) was defined as the time from randomization to death of any cause. Surviving patients were censored at the date of last follow-up. The median OS with 95% CI was estimated using the Kaplan Meier method. (NCT00453154)
Timeframe: Up to 3 years

Interventionmonths (Median)
Arm I (Combination Chemotherapy + Sunitinib Maintenance)9.0
Arm II (Combination Chemotherapy + Placebo Maintenance)6.9

[back to top]

Number of Individuals With Adverse Events

Drug toxicities will be evaluated during treatment period and 30 days post treatment. Toxicities will be assessed using Common Terminology Criteria for Adverse Events (CTCAE 3.0) criteria. Grade 3 or 4 adverse events were reported (NCT00454324)
Timeframe: 10 weeks

,
InterventionParticipants (Count of Participants)
NeutropeniaAnemiaThrombocytopeniaSensory neuropathyPainFatigueNauseaVomitingDiarrhea
Arm A843340001
Arm B543001321

[back to top]

Progression Free Survival (PFS)

Defined as the time between trial enrollment to disease progression or death (whichever occurs first) or date of last contact (NCT00454324)
Timeframe: Through the end of the study, an average of approximately 8 months

InterventionMonths (Median)
Arm A5.8
Arm B5.2

[back to top]

Overall Response Rate

Radiological imaging should be performed every 12 weeks, to ascertain the overall (or objective) response rate (Complete Response or Partial Response) according to the RECIST guidelines. Complete Response (CR) - Disappearance of all target lesions. Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Overall Response Rate = CR+PR. (NCT00454324)
Timeframe: 12 weeks

Interventionpercentage of participants (Number)
Arm A79
Arm B85

[back to top]

1-year Overall Survival (OS)

Percentage of participants from the start of treatment with the disease that are still alive. (NCT00454324)
Timeframe: every 12 weeks for 1 year

Interventionpercentage of participants (Number)
Arm A36
Arm B42

[back to top]

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Pemetrexed

AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). (NCT00454649)
Timeframe: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9

Interventionng*hr/mL (Mean)
Axitinib + Pemetrexed + Cisplatin (Cohort 9)133032.97

[back to top]

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Paclitaxel

AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). (NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4

Interventionng*hr/mL (Mean)
Axitinib + Paclitaxel (Cohort 4)5683.55
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)19959.91

[back to top]

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Gemcitabine

AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8

Interventionng*hr/mL (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)10991.16

[back to top]

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Docetaxel

AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). (NCT00454649)
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5

Interventionng*hr/mL (Mean)
Axitinib + Docetaxel (Cohort 5)3478.49

[back to top]

Area Under the Curve From Time Zero to Extrapolated Infinite Time [AUC (0-∞)] for Carboplatin

AUC (0-∞) = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-∞). It is obtained from AUC (0-t) plus AUC (t-∞). (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3

Interventionng*hr/mL (Mean)
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)55580.26

[back to top]

Apparent Oral Clearance (CL/F) for Capecitabine

Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes and F is the absolute oral bioavailability. Apparent oral clearance(CL/F) is obtained following oral administration. (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7

InterventionLiter/hr (Mean)
Axitinib + Capecitabine (Cohort 6)209.05
Axitinib + Capecitabine (Cohort 7)314.12

[back to top]

Plasma Decay Half Life (t1/2) for Pemetrexed

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9

Interventionhr (Mean)
Axitinib + Pemetrexed + Cisplatin (Cohort 9)2.77

[back to top]

Plasma Decay Half Life (t1/2) for Paclitaxel

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4

Interventionhr (Mean)
Axitinib + Paclitaxel (Cohort 4)12.51
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)8.36

[back to top]

Plasma Decay Half Life (t1/2) for Gemcitabine

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8

Interventionhr (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)0.29

[back to top]

Plasma Decay Half Life (t1/2) for Docetaxel

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5

Interventionhr (Mean)
Axitinib + Docetaxel (Cohort 5)11.49

[back to top]

Plasma Decay Half Life (t1/2) for Cisplatin

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9

Interventionhr (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)2.61
Axitinib + Pemetrexed + Cisplatin (Cohort 9)3.91

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Carboplatin

(NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3

Interventionng/mL (Mean)
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)23383.33

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Cisplatin

(NCT00454649)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9

Interventionng/mL (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)1680.54
Axitinib + Pemetrexed + Cisplatin (Cohort 9)1176.00

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Docetaxel

(NCT00454649)
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5

Interventionng/mL (Mean)
Axitinib + Docetaxel (Cohort 5)3130.00

[back to top]

Plasma Decay Half Life (t1/2) for Axitinib (AG-013736)

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9

Interventionhr (Mean)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)2.75
Axitinib + Paclitaxel + Carboplatin (Cohort 2)2.90
Axitinib + Paclitaxel + Carboplatin (Cohort 3)2.80
Axitinib + Paclitaxel (Cohort 4)1.45
Axitinib + Docetaxel (Cohort 5)4.07
Axitinib + Capecitabine (Cohort 6)3.85
Axitinib + Capecitabine (Cohort 7)3.64
Axitinib + Gemcitabine + Cisplatin (Cohort 8)2.68
Axitinib + Pemetrexed + Cisplatin (Cohort 9)5.02

[back to top]

Plasma Decay Half Life (t1/2) for Carboplatin

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3

Interventionhr (Mean)
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)2.62

[back to top]

Plasma Decay Half Life (t1/2) for Capecitabine

t1/2 is the time measured for the plasma concentration to decrease by one half. (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7

Interventionhr (Mean)
Axitinib + Capecitabine (Cohort 6)0.85
Axitinib + Capecitabine (Cohort 7)1.44

[back to top]

Apparent Oral Clearance (CL/F) for Axitinib (AG-013736)

Clearance (CL) of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes and F is the absolute oral bioavailability. Apparent oral clearance(CL/F) is obtained following oral administration. (NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9

InterventionLiter/hour (L/hr) (Mean)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)49.39
Axitinib + Paclitaxel + Carboplatin (Cohort 2)40.72
Axitinib + Paclitaxel + Carboplatin (Cohort 3)29.73
Axitinib + Paclitaxel (Cohort 4)65.69
Axitinib + Docetaxel (Cohort 5)14.35
Axitinib + Capecitabine (Cohort 6)26.64
Axitinib + Capecitabine (Cohort 7)83.46
Axitinib + Gemcitabine + Cisplatin (Cohort 8)50.05
Axitinib + Pemetrexed + Cisplatin (Cohort 9)25.10

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Gemcitabine

(NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8

Interventionng/mL (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)20635.29

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Paclitaxel

(NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4

Interventionng/mL (Mean)
Axitinib + Paclitaxel (Cohort 4)3698.33
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)6105.00

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Pemetrexed

(NCT00454649)
Timeframe: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9

Interventionng/mL (Mean)
Axitinib + Pemetrexed + Cisplatin (Cohort 9)83925.00

[back to top]

Maximum Tolerated Dose (MTD) of Axitinib (AG-013736) in Combination With Chemotherapy

MTD defined as the dose level at which more than 1 out of 6 participants experienced a dose limiting toxicity (DLT). DLT included grade (Gr) 4 neutropenia or thrombocytopenia, greater than or equal to (>=) Gr 3 nonhematological toxicities or >=0.5 teaspoon/day hemoptysis or >=2 gram /24 hours proteinuria or inability to resume background chemotherapy or axitinib (AG-013736) dosing within 14 days of stopping due to treatment related toxicity. (NCT00454649)
Timeframe: Baseline to withdrawal from study or Day 21 of Cycle 1 [all cohorts except cohort 4 (Day 28 of Cycle 1)]

Interventionmg BID (Number)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)5
Axitinib + Paclitaxel + Carboplatin (Cohort 2)5
Axitinib + Paclitaxel + Carboplatin (Cohort 3)5
Axitinib + Paclitaxel (Cohort 4)5
Axitinib + Docetaxel (Cohort 5)NA
Axitinib + Capecitabine (Cohort 6)5
Axitinib + Capecitabine (Cohort 7)5
Axitinib + Gemcitabine + Cisplatin (Cohort 8)5
Axitinib + Pemetrexed + Cisplatin (Cohort 9)5

[back to top]

Percentage of Participants With Objective Response

Percentage of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Confirmed response are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as the disappearance of all lesions (target and/or non target). PR are those with at least 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. (NCT00454649)
Timeframe: Baseline and thereafter every 2 cycles up to disease progression or discontinuation from study or up to 155 weeks

InterventionPercentage of Participants (Number)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)100.0
Axitinib + Paclitaxel + Carboplatin (Cohort 2)0
Axitinib + Paclitaxel + Carboplatin (Cohort 3)35.0
Axitinib + Paclitaxel (Cohort 4)66.7
Axitinib + Docetaxel (Cohort 5)50.0
Axitinib + Capecitabine (Cohort 6)11.1
Axitinib + Capecitabine (Cohort 7)11.8
Axitinib + Gemcitabine + Cisplatin (Cohort 8)23.8
Axitinib + Pemetrexed + Cisplatin (Cohort 9)0

[back to top]

Plasma Clearance (CL) for Carboplatin

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma. (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 5 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3

InterventionL/hr (Mean)
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)12.57

[back to top]

Plasma Clearance (CL) for Cisplatin

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma. (NCT00454649)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9

InterventionL/hr (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)46.31
Axitinib + Pemetrexed + Cisplatin (Cohort 9)46.80

[back to top]

Plasma Clearance (CL) for Docetaxel

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma. (NCT00454649)
Timeframe: 0 (pre-dose), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 5

InterventionL/hr (Mean)
Axitinib + Docetaxel (Cohort 5)42.96

[back to top]

Area Under the Curve From Time Zero to Time 8 Hours [AUC (0-8)] for Cisplatin

AUC (0-8) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 8 hours (0-8). (NCT00454649)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 5, 7 hr after start of infusion on Day 1 of Cycle 2 for cohort 8 and 9

Interventionng*hr/mL (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)2932.43
Axitinib + Pemetrexed + Cisplatin (Cohort 9)2703.92

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Capecitabine

(NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7

Interventionng/mL (Mean)
Axitinib + Capecitabine (Cohort 6)10808.00
Axitinib + Capecitabine (Cohort 7)10588.38

[back to top]

Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736)

(NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9

Interventionng/mL (Mean)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)5.97
Axitinib + Paclitaxel + Carboplatin (Cohort 2)23.36
Axitinib + Paclitaxel + Carboplatin (Cohort 3)42.58
Axitinib + Paclitaxel (Cohort 4)44.58
Axitinib + Docetaxel (Cohort 5)67.96
Axitinib + Capecitabine (Cohort 6)37.51
Axitinib + Capecitabine (Cohort 7)43.97
Axitinib + Gemcitabine + Cisplatin (Cohort 8)40.97
Axitinib + Pemetrexed + Cisplatin (Cohort 9)31.53

[back to top]

Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Capecitabine

AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24). (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 1, 2, 3, 4, 6, 8 hr post-dose on Day 1 of Cycle 2 for cohort 6 and 7

Interventionng*hr/mL (Mean)
Axitinib + Capecitabine (Cohort 6)20534.52
Axitinib + Capecitabine (Cohort 7)22163.88

[back to top]

Area Under the Curve From Time Zero to Time 24 Hours [AUC (0-24)] for Axitinib (AG-013736)

AUC (0-24) = Area under the plasma concentration versus time curve from time zero (pre-dose) to time 24 hours (0-24). (NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 4, 6, 8 hr post-dose on Day -1 for cohort 1, 2, 3, 5 and 8; on Day 22 of Cycle 1 for cohort 4; on Day 18 of Cycle 1 for cohorts 6 and 7; 0 (pre-dose), 1.2, 2.2, 3.2, 4.2, 6.2, 8.2 hr post-dose on Day -1 for cohort 9

Interventionnanogram*hour/milliliter (ng*hr/mL) (Mean)
Axitinib + Paclitaxel + Carboplatin (Cohort 1)61.58
Axitinib + Paclitaxel + Carboplatin (Cohort 2)242.41
Axitinib + Paclitaxel + Carboplatin (Cohort 3)475.18
Axitinib + Paclitaxel (Cohort 4)154.43
Axitinib + Docetaxel (Cohort 5)780.99
Axitinib + Capecitabine (Cohort 6)365.95
Axitinib + Capecitabine (Cohort 7)449.99
Axitinib + Gemcitabine + Cisplatin (Cohort 8)416.30
Axitinib + Pemetrexed + Cisplatin (Cohort 9)420.64

[back to top]

Plasma Clearance (CL) for Gemcitabine

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma. (NCT00454649)
Timeframe: 0 (pre-dose), 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4 hr after start of infusion on Day 1 of Cycle 2 for cohort 8

InterventionL/hr (Mean)
Axitinib + Gemcitabine + Cisplatin (Cohort 8)224.36

[back to top]

Plasma Clearance (CL) for Paclitaxel

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma. (NCT00454649)
Timeframe: 0 (pre-dose), 1, 2, 3, 3.25, 3.5, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 1-3; 0 (pre-dose), 0.5, 1, 2, 3, 4, 5, 6, 8, 24, 30 hr after start of infusion on Day 1 of Cycle 2 for cohort 4

InterventionL/hr (Mean)
Axitinib + Paclitaxel (Cohort 4)30.48
Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3)21.61

[back to top]

Plasma Clearance (CL) for Pemetrexed

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the plasma. (NCT00454649)
Timeframe: 0 (pre-dose), 10 minutes (end of infusion), 0.5, 1, 1.5, 2, 4, 6, 8 hr after end of infusion on Day 1 of Cycle 2 for cohort 9

InterventionL/hr (Mean)
Axitinib + Pemetrexed + Cisplatin (Cohort 9)7.26

[back to top]

Time to Progression (TTP), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease

Time to Progression (TTP) is defined as the interval between the date of treatment initiation and the date of progressive disease. Progression is defined using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0). Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or unequivocal progression of non-target lesions or the appearance of one or more new lesions. (NCT00456261)
Timeframe: From the date of treatment initiation until the date of first documented PD or date of last study contact or date of other therapy begins up to 18 months

Interventionmonths (Median)
Bevacizumab/Pemetrexed/Gemcitabine4.7
Bevacizumab/Pemetrexed/Carboplatin10.2

[back to top]

Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

OS is defined as the time from the date of study entry until the date of death due to any cause. In the absence of confirmation of death or lack of data beyond follow-up period, the survival time was censored to the last date the participant was known to be alive. (NCT00456261)
Timeframe: From date of study entry until the date of death from any cause or the date the patient was last known alive, up to 18 months

Interventionmonths (Number)
Bevacizumab/Pemetrexed/Gemcitabine7.5
Bevacizumab/Pemetrexed/Carboplatin14.8

[back to top]

Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment

Overall response rate (ORR) is defined as the percentage of patients who have a partial or complete response to therapy. Responses were assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.0). Complete Response: Disappearance of all target lesions, and disappearance of all non-target lesions. Partial Response: At least a 30% decrease in the sum of the longest diameter of target lesions (taking as reference the baseline sum of longest diameters) (NCT00456261)
Timeframe: From date of treatment initiation to end of study treatment up to 18 months

Interventionpercentage of patients (Number)
Bevacizumab/Pemetrexed/Gemcitabine35
Bevacizumab/Pemetrexed/Carboplatin35

[back to top]

Progression Free Survival (PFS)

The primary outcome was the proportion of patients who achieved progression free survival (PFS) of five months. PFS was defined as time to progression or any-cause mortality, whichever came first. (NCT00461851)
Timeframe: Upon completion of study

Interventionmonths (Median)
Chemotherapy Plus Sorafenib9.5

[back to top]

Dose Ruction (Toxicity)

To determine the toxicity of combination therapy with sorafenib, gemcitabine and carboplatin, dose reductions by drug are reported. The number of patients that were reduced in dosage are reported here. (NCT00461851)
Timeframe: Upon completion of study

InterventionParticipants (Count of Participants)
Dose Reduction: GemcitabineDose Reduction: CarboplatinDose Reduction: Sorafenib
Chemotherapy Plus Sorafenib1559

[back to top]

The Number of Patients Who Experience at Least One Grade 3 or Higher CTC Version 4 Toxicity.

(NCT00467051)
Timeframe: Two cycles of chemotherapy; expected to be 42 days of treatment.

InterventionParticipants (Count of Participants)
Experimental18

[back to top]

Response Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

Patients who demonstrate a PR or CR, as defined below, will be considered as responders. RECIST criteria: CR (complete response) = disappearance of all target lesions, PR (partial response) = 30% decrease in the sum of the longest diameter of target lesions, PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions and SD (stable disease) = small changes that do not meet above criteria. (NCT00467051)
Timeframe: At baseline (day 1) and after completion of protocol therapy (2 cycles or 42 days)

Interventionparticipants (Number)
ResponderNon-Responder
Treatment (Chemotherapy, Biological Therapy)128

[back to top]

Overall Survival

(NCT00469898)
Timeframe: On study date to death

InterventionMonths (Median)
Therapeutic Intervention9

[back to top]

Time to Progression

Time to progression in months (NCT00469898)
Timeframe: 9.9 months (on study date to progression)

InterventionMonths (Median)
Therapeutic Intervention5

[back to top]

Number of Patients With Adverse Events

Number of participants with adverse events, according to grade of event, using the NCI Common Toxicity Criteria (version 2.0) grading system to assign a grade to each event (NCT00469898)
Timeframe: date off treatment or progression of disease, up to 18 weeks

Interventionparticipants (Number)
Grade 1Grade 2Grade 3Grade 4Grade 5
Therapeutic Intervention132629104

[back to top]

Patient Response

"Patient response to treatment:~Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started Complete response (CR): disappearance of all target lesions Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD" (NCT00469898)
Timeframe: 1.66 months (average duration, on treatment date to best response date)

Interventionparticipants (Number)
Complete ResponseNot AssessedNot EvaluablePartial ResponseProgressive DiseaseStable DiseaseUnknown
Therapeutic Intervention212271215

[back to top]

Number of Participants Who Had a Disease Response to Treatment

Response to treatment is defined as a complete response (CR) or partial response (PR) to treatment. Confirmation of response required a second assessment performed at least 4 weeks after the initial assessment. (PR is defined as at least a 30% reduction in sum of the longest diameter of all target lesions and no increase in non-target lesions). (NCT00473889)
Timeframe: Every 42 days from start of treatment until disease response

,
InterventionParticipants (Number)
ResponderNon-Responder
Placebo + Paclitaxel + Carboplatin3687
Vorinostat + Paclitaxel + Carboplatin2897

[back to top]

Progression Free Survival

Defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Disease progression is defined as at least a 20% increase in sum of the longest diameter of all target lesions, the appearance of a new lesion, or an increase in non-target lesions. (NCT00473889)
Timeframe: Start of treatment to disease progression or death

InterventionMonths (Median)
Vorinostat + Paclitaxel + Carboplatin4.3
Placebo + Paclitaxel + Carboplatin5.5

[back to top]

Overall Survival

Defined as the time from date of randomization to death due to any cause. Patients without documented death at the time of the final analysis will be censored at the date of the last follow-up. (NCT00473889)
Timeframe: Start of treatment to death

InterventionMonths (Median)
Vorinostat + Paclitaxel + Carboplatin11.0
Placebo + Paclitaxel + Carboplatin14.0

[back to top]

"Best Clinical Response Expressed as Percentage of Participants Treated With Combination Regimen of Weekly Abraxane® and Carboplatin Plus Biweekly Bevacizumab to Treat Women With Stage IV or Inoperable Stage III Triple Negative Metastatic Breast Cancer."

Best clinical response is based on RECIST criteria, the proportion in each response category along with the exact binomial confidence intervals are estimated. Toxicity summaries are also provided. (NCT00479674)
Timeframe: 5 years

Interventionpercentage of participants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive Disease
Abraxane, Carboplatin, Bevacizumab186985

[back to top]

Median Proportion Progression-free as Estimated by Kaplan-Meier Methods

PFS was defined as time from trial enrollment to disease progression or death, whichever occurred first. (NCT00479674)
Timeframe: 5 years

Interventionmonths (Median)
Abraxane, Carboplatin, Bevacizumab15

[back to top]

Progression-free Survival

Evaluated using the Kaplan-Meier method. Compared between arms using the log-rank test. (NCT00481078)
Timeframe: Up to 1 year

InterventionMonths (Median)
Arm I (Vorinostat, Paclitaxel, Carboplatin)6
Arm II (Placebo, Paclitaxel, Carboplatin)4.1

[back to top]

Overall Survival

Evaluated using the Kaplan-Meier method. Compared between arms using the log-rank test. (NCT00481078)
Timeframe: Up to 1 year

InterventionMonths (Median)
Arm I (Vorinostat, Paclitaxel, Carboplatin)13
Arm II (Placebo, Paclitaxel, Carboplatin)9.7

[back to top]

Response Rate

"Each patient will be assigned one of the following categories: 1) complete response, 2) partial response, 3) stable disease, 4) progressive disease, 5) early death from malignant disease, 6) early death from toxicity, 7) early death because of other cause, or 9) unknown (not assessable, insufficient data).~Patients with confirmed CR or PR according to the RECIST criteria were considered to have responded to treatment." (NCT00481078)
Timeframe: Assessed every two cycles

Interventionpercentage of responding patients (Number)
Arm I (Vorinostat, Paclitaxel, Carboplatin)34
Arm II (Placebo, Paclitaxel, Carboplatin)12.5

[back to top]

Phase 2 - Time to Progression

Time to disease progression was measured from randomization of Study Phase 2 to the first observation of disease progression according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Disease progression is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. (NCT00482014)
Timeframe: Phase 2 randomization to measured disease progression up to 24 months

Interventionmonths (Median)
Pemetrexed + Carboplatin Treatment Group8.8
Pemetrexed + Cisplatin Treatment Group13.1

[back to top]

Phase 1 - Percentage of Participants With Complete Response or Partial Response (Response Rate)

Response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. (NCT00482014)
Timeframe: Phase 1 enrollment to the end of the study treatment up to Week 11

,
Interventionpercentage of participants (Number)
Complete Response (CR)Partial Response (PR)
Pemetrexed + Carboplatin Treatment Group011.1
Pemetrexed + Cisplatin Treatment045.5

[back to top]

Phase 1 - Pharmacology Toxicity: Number of Participants With Dose Limiting Toxicities (DLTs)

Phase 1 pharmacology toxicity was defined as the number of participants experiencing dose limiting toxicities (DLTs). DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) >7 days, febrile neutropenia, ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations), and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis). Grade 5 events are the events leading to the death. (NCT00482014)
Timeframe: Phase 1 enrollment up to Week 11

,
Interventionparticipants (Number)
Grade 5 Pneumocystis jiroveci pneumoniaGrade 5 Hemoptysis (pemetrexed+Cisplatin30 mg/m² )
Pemetrexed + Carboplatin Treatment Group10
Pemetrexed + Cisplatin Treatment01

[back to top]

Phase 2 - Percentage of Participants With Complete Response or Partial Response (Response Rate)

Response rate is the percentage of participants with complete response (CR) or partial response (PR), as assessed according to the Response Evaluation Criteria In Solid Tumors (RECIST) guidelines. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Response rate is calculated as a total number of participants with CR or PR divided by the total number of participants treated multiplied by 100. (NCT00482014)
Timeframe: Phase 2 randomization to the end of the treatment up to 30.0 months

,
Interventionpercentage of participants (Number)
Complete Response (CR)Partial Response (PR)
Pemetrexed + Carboplatin Treatment Group6.545.7
Pemetrexed + Cisplatin Treatment Group3.842.3

[back to top]

Phase 2 - Pharmacology Toxicity: Number of Participants With Adverse Events

Phase 2 pharmacology toxicity was defined as the number of participants who experienced serious adverse events or all other nonserious adverse events during the study. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Events section. (NCT00482014)
Timeframe: Phase 2 randomization to the end of the study treatment up to 30.0 months

,
Interventionparticipants (Number)
Serious Adverse EventsOther Nonserious Adverse Events
Pemetrexed + Carboplatin Treatment Group2144
Pemetrexed + Cisplatin Treatment Group1951

[back to top]

Phase 2 - Survival Probability at 2 Years

(NCT00482014)
Timeframe: Phase 2 randomization up to 2 years

Interventionpercentage survival (Mean)
Pemetrexed + Carboplatin Treatment Group45.4
Pemetrexed + Cisplatin Treatment Group58.4

[back to top]

Phase 2 - Median Survival

(NCT00482014)
Timeframe: Phase 2 randomization to death as the result of any cause up to 30.0 month

Interventionmonths (Median)
Pemetrexed + Carboplatin Treatment Group18.7
Pemetrexed + Cisplatin Treatment Group27.0

[back to top]

Phase 1 - Maximum Tolerated Dose (MTD) of Cisplatin

MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) lasting >7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis). (NCT00482014)
Timeframe: Phase 1 enrollment to the end of study treatment up to Week 11

Interventionmilligrams/meter squared (mg/m²) (Number)
Pemetrexed + Cisplatin Treatment GroupNA

[back to top]

Phase 1 - Maximum Tolerated Dose (MTD) of Carboplatin

MTD was defined as a dose at which the occurrence of at least 2 dose-limiting toxicities (DLTs) was observed. DLT was defined as any of the following events occurring during the entire radiation therapy (RT) course, including a 2-week recovery period following completion of RT: Grade 4 neutropenia (<0.5 x 10^9 cells per liter) lasting >7 days, febrile neutropenia; ≥Grade 3 neutropenia with fever >38.5 degrees Celsius (°C), Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with ≥Grade 2 bleeding, ≥Grade 3 nonhematologic toxicity (excluding nausea, vomiting, and transaminase elevations) and ≥Grade 3 pulmonary or esophageal toxicity (radiation-related pneumonitis or esophagitis). (NCT00482014)
Timeframe: Phase 1 enrollment to the end of study treatment up to Week 11

Interventionmilligram/milliliter*minute (mg/mL*min) (Number)
Pemetrexed + Carboplatin Treatment GroupNA

[back to top]

Objective Response Rate Categorized by Subgroup

The number of participants achieving an objective response (as determined by RECIST) categorized by treatment cohort and whether the treatment was first or second line treatment. First line treatment means that the drug used was the first drug used for the treatment of the primary cancer. Second line treatment means that a first line treatment failed to produce the desired response, so a new drug was used for treatment. (NCT00483223)
Timeframe: 3 years

InterventionParticipants (Count of Participants)
Cisplatin72090026Carboplatin72090026
Second line: ResponseSecond line: No responseFirst line: ResponseFirst line: No response
Cisplatin or Carboplatin12
Cisplatin or Carboplatin22
Cisplatin or Carboplatin2
Cisplatin or Carboplatin7
Cisplatin or Carboplatin27
Cisplatin or Carboplatin0
Cisplatin or Carboplatin8

[back to top]

Objective Response Rate

"Objective response rate (ORR) (complete response [CR]+ partial response [PR]) by RECIST (Response Evaluation Criteria In Solid Tumors).~Complete Response (CR): Disappearance of all target lesions~Partial Response (PR): At least a 30% decrease in the sum of the LD (longest diameter) of target lesions, taking as reference the baseline sum LD~Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started~Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions" (NCT00483223)
Timeframe: 3 years

InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable Disease > 6 MonthsProgressive DiseaseNot Evaluable
Cisplatin or Carboplatin3194573

[back to top]

Progression Free Survival and Overall Survival

Median progression free survival and overall survival (progression determined using RECIST) during a median follow-up time of 50 months. (NCT00483223)
Timeframe: 5 years

InterventionMonths (Median)
Median Progression Free SurvivalMedian Overall Survival
Cisplatin or Carboplatin2.911

[back to top]

Response Rate Categorized by p63/p73 Ratio

Response rate categorized by pre-specified ΔNp63/TAp73 expression ratio cutoff in the primary tumors from this patient cohort as a bio-marker to predict response to cisplatin or carboplatin. Response is defined as partial or completed response as determined by RECIST. Expression ratio was measured using quantitative RT-PCR (Reverse transcription polymerase chain reaction). (NCT00483223)
Timeframe: 3 years

InterventionParticipants (Count of Participants)
p63/p73 > 272090026p63/p73 < 272090026
ResponseNo Response
Cisplatin or Carboplatin9
Cisplatin or Carboplatin24
Cisplatin or Carboplatin5
Cisplatin or Carboplatin23

[back to top]

Phase 2 - Time to Treatment Failure

Time to treatment failure (TTTF) is defined as the time from the date of study enrollment to the date of the first observation of disease progression, death from any cause, or early discontinuation of treatment (any reason). For patients who are alive, progression-free, and have not discontinued early at the time of analysis, TTTF will be censored at the date of the last objective progression-free disease assessment. (NCT00489359)
Timeframe: First treatment to discontinuation of study drug, progressive disease, or death (up to 31 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin Phase 27.1

[back to top]

Phase 2 - Time to Response (TTR)

Response is defined as CR (Complete Response) or PR (Partial Response) per RECIST criteria. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT00489359)
Timeframe: First treatment to response (up to 31 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin Phase 21.8

[back to top]

Phase 2 - Time to Disease Progression

Time to objective progressive disease (TTPD) is defined as the time from the date of study enrollment to the date of objectively determined Progressive Disease (PD). For patients who die without objective PD (including death from study disease), TTPD will be censored at the date of the last objective progression-free disease assessment. For patients who are still alive at the time of analysis, and who do not have PD, TTPD will be censored at the date of the last objective progression-free disease assessment. (NCT00489359)
Timeframe: baseline to measured progressive disease (up to 31 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin Phase 29.5

[back to top]

Phase 2 - Progression-Free Survival

Progression-free survival (PFS) is defined as the time from the date of study enrollment to the date of objectively determined PD or death from any cause, whichever comes first. For patients who are still alive at the time of analysis, and who do not have PD, PFS will be censored at the date of the last objective progression-free disease assessment. (NCT00489359)
Timeframe: baseline to measured progressive disease (up to 31 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin Phase 29.4

[back to top]

Phase 2 - Number of Participants With Adverse Events (Toxicity)

A listing of adverse events is located in the Reported Adverse Event module. (NCT00489359)
Timeframe: baseline through end of Phase 2 (up to 31 months)

Interventionparticipants (Number)
Serious Adverse EventsOther Adverse Events
Pemetrexed/Carboplatin Phase 21563

[back to top]

Phase 1 - Number of Participants With Tumor Response

Patients were analyzed by Cancer Antigen-125 (CA-125) response criteria and RECIST guidelines. Possible evaluations include: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the size of target lesions. Progressive Disease (PD): At least a 20% increase in the size of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT00489359)
Timeframe: baseline measured to progressive disease (up to 18 months)

InterventionParticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)
Pemetrexed/Carboplatin Phase 112412

[back to top]

Phase 2 - Percentage of Participants With Overall Tumor Response (Response Rate)

"Response is defined as CR (Complete Response) or PR (Partial Response) per Response Evaluation Criteria in Solid Tumor (RECIST criteria). Possible evaluations include: CR: Disappearance of all target lesions. PR: At least a 30% decrease in the size of target lesions.~Response rate (%) = (number of patients with CR+PR/number of patients in Phase 2)*100" (NCT00489359)
Timeframe: baseline to measured progressive disease (PD) (up to 18 months)

Interventionpercentage of participants (Number)
Pemetrexed/Carboplatin Phase 232.8

[back to top]

Phase 1 - Number of Dose-Limiting Toxicities (DLTs)

"The following toxicities were considered DLT: CTCAE Grade 4 neutropenia (absolute neutrophil count [ANC] <0.5 × 10^9/L lasting ≥7 days. Febrile neutropenia (ANC <1.0 × 10^9/L, fever 38.5°C, and no documented infection). CTCAE Grade 4 thrombocytopenia (platelets <25.0 × 10^9/L).~Any hemorrhage with CTCAE Grade ≥3 thrombocytopenia (50.0 × 10^9/L). CTCAE Grade ≥3 nonhematologic toxicity (excluding nausea, vomiting, or CTCAE Grade 3 alanine transaminase (ALT) or aspartate aminotransferase (AST) that returned to baseline prior to next treatment).~Treatment delay more than 1 week due to toxicity." (NCT00489359)
Timeframe: baseline through end of Phase 1 (up to 18 months)

InterventionDLT events (Number)
Number of DLT EventsDLT Event: Grade 4 Neutropenia
Pemetrexed/Carboplatin Phase 111

[back to top]

Phase 1 - Recommended Dose of Pemetrexed for Phase 2

MTD was to be used as Phase 2 recommended dose. MTD was to be determined by increasing doses of pemetrexed up to 900 mg/m^2 based on observed pattern of dose limiting toxicity (DLT: See Outcome #3). If none of 3 initial participants at a given level had a DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had a DLT in Cycle 1 at a dose level, that dose level was considered the MTD. However, based on results from another Phase 2 Study (NCT00109096), further dose escalations were not explored and dose was selected based on results of that Phase 2 Study. (NCT00489359)
Timeframe: baseline measured to progressive disease (up to 18 months)

Interventionmg/m^2 (milligrams per square meter) (Number)
Pemetrexed/Carboplatin Phase 1500

[back to top]

Phase 1 - Recommended Area Under the Curve (AUC) Dose of Carboplatin for Phase 2

MTD was to be used as Phase 2 recommended dose. MTD determined by increasing doses up to AUC 6 mg/mL*min based on pattern of DLT (Outcome #3). If none of 3 initial participants at given level had DLT in Cycle 1, enrollment proceeded to next dose level. If at least 2 participants had DLT in Cycle 1 at dose level, that dose level was considered MTD. However, based on results from Phase 2 Study (NCT00109096), further dose escalations were not explored: carboplatin dose was selected based on standard dose employed in control arm of first-line therapy for epithelial ovarian cancer (Bookman 2006). (NCT00489359)
Timeframe: baseline measured to progressive disease (up to 18 months)

Interventionmg/mL*min (Number)
Pemetrexed/Carboplatin Phase 16

[back to top]

Phase 2 - Duration of Response (DOR)

Duration of response is defined as the time from first observation of Complete Response or Partial Response to the first observation of Progressive Disease or death from any cause. For patients who are still alive at the time of analysis, and who do not have Progressive Disease, duration of response will be censored at the date of the last objective progression-free disease assessment. (NCT00489359)
Timeframe: time of response to progressive disease (up to 31 months)

InterventionMonths (Median)
Pemetrexed/Carboplatin Phase 29.1

[back to top]

Phase 1 - Number of Participants With Adverse Events (Toxicity)

A listing of adverse events is located in the Reported Adverse Event module. (NCT00489359)
Timeframe: baseline measured to progressive disease (up to 18 months)

InterventionParticipants (Number)
Serious Adverse EventsOther Adverse Events
Pemetrexed/Carboplatin Phase 1219

[back to top]

Pharmacology Toxicity

Radiation Therapy Oncology Group (RTOG) criteria were used for assessing toxicity. Toxicity grade reflected the most severe degree occurring during the evaluated period, not an average. When two criteria were available for similar toxicities, the one resulting in the more severe grade was used. Toxiccity grades range from 0 to 5. Toxicity grade = 5 if that toxicity caused the death of the patient. (NCT00494026)
Timeframe: every 21-day cycle for 4 cycles

Interventionparticipants (Number)
Cycle 3: Grade 2 Hematologic White Blood CellCycle 3: Grade 1 PlateletsCycle 3: Grade 3 NeutrophilsCycle 3: Grade 2 HemoglobinCycle 3: Grade 2 HematocritCycle 4: Grade 3 Hematologic White Blood CellCycle 4: Grade 3 PlateletsCycle 4: Grade 2 NeutrophilsCycle 4: Grade 3 HemoglobinCycle 4: Grade 3 Hematocrit
Pemetrexed + Carboplatin1111111111

[back to top]

Overall Survival and Progression Free Survival

"The primary objective was to improve overall survival (OS). Patients are recommended to have follow up 6 weeks after completion of concurrent chemo radiotherapy for the evaluation of acute treatment toxicities, then required every 3 months (+ 1 month) for two years, then every 6 months (+ 1 month) for three years and then annually for the rest of their lives, that is standard of care.~Statistics were performed with Strata/MP 14.2 software. OS was calculated by Kaplan-Meier Methodology (K-M) from the beginning of enrollment to date of death or last follow-up.~Progression-free survival (PFS) was defined from enrollment to any treatment failure or death. PFS will be evaluated by series CT of chest with contrast for every follow up except 6 weeks after the concurrent chemo radiotherapy for two years.~Multivariate Cox proportional hazards modeling was used to examine predictors of OS when adjusting for each of the collected potential confounding variables." (NCT00495170)
Timeframe: The Overall survival (OS): From date of registration to the last follow-up (f/u), or lost to f/u, or death up to 5 years. The progression free survival (PFS): From date of registration to the date of first documented progression or death up to 5 years.

Interventionpercentage of participants (Number)
Overall Survival at 5 yearsProgression Free Survival (PFS)Progression Free Survival at 5 years
Concurrent Proton and Chemotherapy2912.922

[back to top]

Response Rate (RR)

Number of participants per response category. Response to treatment was determined according to Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (NCT00499109)
Timeframe: 6 months

,
Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)
C. Standard of Care Control Arm031
E. Dual Agent Chemotherapy064

[back to top]

Progression Free Survival (PFS)

PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. The data of first documented disease progression or death, as defined by Response Evaluation Criteria In Solid Tumors (RECIST), was recorded, and the time interval from randomization to that date was calculated for each patient and used to generate Kaplan-Meier survival estimates and to calculate the PFS at 6 months. (NCT00499109)
Timeframe: 6 months

Interventionestimated percentage of participants (Number)
E. Dual Agent Chemotherapy52
C. Standard of Care Control Arm56.5

[back to top]

Overall Survival (OS)

OS at 12 months, determined from the date of randomization. The time interval from randomization to the date of death was calculated for each patient and used to generate Kaplan-Meier survival estimates and to calculate the overall survival. (NCT00499109)
Timeframe: 12 months

Interventionestimated percentage of participants (Number)
E. Dual Agent Chemotherapy46.1
C. Standard of Care Control Arm46.6

[back to top]

Outcome of Patients With Stage 4S Neuroblastoma Who Are Unable to Undergo Biopsy for Biology-based Risk Assignment

Kaplan-Meier curves and lifetables of Event Free Survival (EFS) and Overall Survival (OS) rates will be generated to describe the outcome of the stage 4S infants unable to undergo biopsy. (NCT00499616)
Timeframe: From baseline to up to 10 years

Interventionpercentage survival (Number)
OSEFS
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)50.025.0

[back to top]

Comparison Between Reduce Intensity of Therapy for Patients With Stage 4 Neuroblastoma and Favorable Biological Features and Patients < 1 Year of Age With Stage 4 Neuroblastoma Treated on COG-A3961

Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients < 1 yrs of age. (NCT00499616)
Timeframe: Up to 3 years

Interventionpercentage of 3 yr EFS rate (Number)
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)66.7

[back to top]

Comparison Between Reduce Intensity of Therapy for Patients With Unfavorable Histology Neuroblastoma and Patients Unfavorable Histology Neuroblastoma Treated on COG-A3961

Addressed by the interim stopping rule and the comparison, by INSS stage, to the historical EFS rate of the analogous cohort of patients < 1 yrs of age (NCT00499616)
Timeframe: Up to 3 years

Interventionpercentage of 3 yr EFS rate (Number)
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)100.0

[back to top]

Image Defined Risk Factor (IDRF)

Percentage of patients with presence of one or more IDRFs will be calculated. IDRFs describe anatomic features which may make surgical resection more difficult. (NCT00499616)
Timeframe: At baseline

Interventionpercentage of patients (Number)
Group 2 (Chemotherapy, Surgery)54.86
Group 3 (Chemotherapy, Surgery)60.28
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)56.82

[back to top]

Neurologic Symptoms

Percentage of patients with neurologic symptoms will be calculated. Includes patients with paraspinal or intraspinal tumors, including epidural tumors with or without spinal cord compression. Neurologic symptoms include back or extremities neurologic symptoms, motor deficit, abnormal sensation, abnormal bladder/bowel sphincteric function, chronic pain in back or extremities, scoliosis, kyphosis, or clinically relevant/functional abnormality in size or contour of leg or foot. (NCT00499616)
Timeframe: At baseline

Interventionpercentage of patients (Number)
Group 2 (Chemotherapy, Surgery)36.57
Group 3 (Chemotherapy, Surgery)35.46
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)27.27

[back to top]

Overall Survival (OS) Rates

OS time is calculated from date of enrollment until death, or until last contact if the patient is alive. (NCT00499616)
Timeframe: 3 years

Interventionpercentage of participants (Number)
Group 2 (Chemotherapy, Surgery)99.4
Group 3 (Chemotherapy, Surgery)93.5
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)88.4

[back to top]

Reduced Surgical Morbidity for Patients With Stage 4S Neuroblastoma

Descriptive analyses of the proportion of stage 4S infants that experience a surgical or post-operative event. (NCT00499616)
Timeframe: Up to 3 years

InterventionProportion (Number)
Group 2 (Chemotherapy, Surgery)0.18
Group 3 (Chemotherapy, Surgery)0.11
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)0

[back to top]

Second-event-free Survival (E2FS)

E2FS (from time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy. (NCT00499616)
Timeframe: From the time of the first progressive, non-metastatic event until the subsequent occurrence of relapse, progressive disease, secondary malignancy, or death; up to 3 years

InterventionPercentage (Number)
All Patients57.14

[back to top]

Second-Overall Survival

OS (from the time of first event) will be calculated to describe the outcome for patients who have a first progressive, non-metastatic event during Observation and then receive protocol retrieval therapy. (NCT00499616)
Timeframe: From the time of the first progressive, non-metastatic event; up to 3 years

InterventionPercentage (Number)
All Patients85.71

[back to top]

Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Event Free Survival (EFS)

To test the predictive ability of the extent of surgical resection for EFS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection. (NCT00499616)
Timeframe: Up to 10 years

,,
Interventionpercentage of 3 yr EFS survival (Number)
EFS w/complete surgical resectionEFS w/o complete surgical resection
Group 2 (Chemotherapy, Surgery)95.482.2
Group 3 (Chemotherapy, Surgery)88.485.1
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)78.669.2

[back to top]

Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Overall Survival (OS) Rates

To test the predictive ability of the extent of surgical resection for OS, log-rank tests will be performed comparing complete surgical resection vs. without complete surgical resection. (NCT00499616)
Timeframe: Up to 10 years

,,
Interventionpercentage of OS rate (Number)
OS w/complete surgical resectionOS w/o complete surgical resection
Group 2 (Chemotherapy, Surgery)100.099.1
Group 3 (Chemotherapy, Surgery)95.493.5
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)96.486.5

[back to top]

Correlation Between Extent of Surgical Resection With the Maintenance of Local Control, Surgical Complication Rate

To test for the association of the extent of surgical resection (CR vs NCT00499616)
Timeframe: Up to 10 years

,,
InterventionProportion with surgical complications (Number)
CR with complicationsCR with no complications
Group 2 (Chemotherapy, Surgery).32.14
Group 3 (Chemotherapy, Surgery).19.13
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy).18.09

[back to top]

Definitive Determination of the Prognostic Ability of 1p and 11q

Addressed by a descriptive comparison of the EFS and OS rates for patients with 1p loss vs without 1p loss, and for those with unbalanced 11q vs normal 11q. (NCT00499616)
Timeframe: At baseline

Interventionpercentage of 3 yr EFS/OS rate (Number)
EFS Eligible & evaluable patients without 1p lossOS Eligible & evaluable patients without 1p lossEFS Eligible & evaluable patients with normal 11qOS Eligible & evaluable patients with normal 11q
Group 2 (Chemotherapy, Surgery)87.299.487.299.4

[back to top]

Definitive Determination of the Prognostic Ability of 1p and 11q

Addressed by a descriptive comparison of the EFS and OS rates for patients with 1p loss vs without 1p loss, and for those with unbalanced 11q vs normal 11q. (NCT00499616)
Timeframe: At baseline

,
Interventionpercentage of 3 yr EFS/OS rate (Number)
EFS Eligible & evaluable patients without 1p lossOS Eligible & evaluable patients without 1p lossEFS Eligible & evaluable patients with 1p lossOS Eligible & evaluable patients with 1p lossEFS Eligible & evaluable patients with normal 11qOS Eligible & evaluable patients with normal 11qEFS Eligible & evaluable patients w/unbalanced 11qOS Eligible & evaluable patients w/unbalanced 11q
Group 3 (Chemotherapy, Surgery)84.692.894.794.787.593.775.087.5
Group 4 (Chemotherapy, Surgery, Antineoplastic Therapy)65.483.781.895.573.387.765.588.2

[back to top]

Number of Patients With Response

Per World Health Organization (WHO) Tumor Response: Complete Response (CR), Partial Response (PR) or Progressive Disease (PD). CR defined as disappearance of all target lesions, PR as > = 30% decrease in sum of longest dimensions of target lesions with reference baseline sum longest dimensions and if CA 125 levels declined by >50%, provided target lesion size did not increase by >20% on imaging, and PD as >20% increase in sum of longest dimensions of target lesions taking as references smallest sum of longest dimensions recorded since treatment started, or appearance of 1 or > new lesions. (NCT00501644)
Timeframe: Follow up CT scans after every 3 courses of treatment and following completion of all treatments.

InterventionParticipants (Number)
Complete ResponsePartial ResponseProgressive Disease
Chemoimmunotherapy92124

[back to top]

Number of Participants With Overall Response

Overall response rate including complete (CR) and partial responses (PR) with measurable disease using Response Evaluation Criteria In Solid Tumors (RECIST) assessment. CR: Disappearance of all target and non-target lesions; no evidence of new lesions documented by 2 disease assessments at least 4 weeks apart. PR: At least 30% decrease in sum of longest dimensions (LD) of all target measurable lesions reference baseline sum of LD; no unequivocal progression of non-target lesions and no new lesions. Documentation by 2 disease assessments at least 4 weeks apart is required. (NCT00502203)
Timeframe: 24 Months

Interventionparticipants (Number)
Paclitaxel + Carboplatin8

[back to top]

Overall Survival

(NCT00507429)
Timeframe: From randomization to date last known alive

Interventionmonths (Median)
Arm 1, Active: CA4P + Carboplatin + Paclitaxel5.2
Arm 2, Comparator: Carboplatin + Paclitaxel4.0

[back to top]

To Determine Percentage of 1 Year Survival

(NCT00507429)
Timeframe: from randomization through end of study visit

Interventionpercentage of participants (Number)
Arm 1, Active: CA4P + Carboplatin + Paclitaxel26
Arm 2, Control: Carboplatin + Paclitaxel9

[back to top]

Median Time to Progression (TTP)

TTP defined as time of registration on study till disease progression. Disease status evaluated at the end of course 1 (up to 84 days after day 1 of cycle 1) and at the end of course 2 (up to 168 days after day 1 of cycle 1). (NCT00514540)
Timeframe: Baseline to evaluation at end of course 2 (up to 168 days) then every 2 months for disease progression. Follow up every 6 months and overall study period was six and half years.

Interventionmonths (Median)
First-Line: Carboplatin + Docetaxel5.1
Second-Line: Etoposide + Cisplatin3.0

[back to top]

Response Rate of Salvage Chemotherapy With Etoposide Plus Cisplatin Following Treatment With Docetaxel Plus Carboplatin.

Response rate is the number of participants with response compared to total. Response defined as the absence of disease progression compared to the participant's baseline evaluation, and the time to a serious adverse event (SAE), defined as grade 3 or 4 neurotoxicity or death. (NCT00514540)
Timeframe: Evaluated at the end of course 1 (up to 84 days after day 1 of cycle 1) and at the end of course 2 (up to 168 days after day 1 of cycle 1)

Interventionparticipants (Number)
Second-Line: EP, Course 143
Second-Line: EP, Course 224

[back to top] [back to top]

Consolidation Objective Response Rate

Consolidation objective response (OR) was based on RECIST 1.0 criteria with OR defined as achieving partial response (PR) or complete response (CR). Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. If CA125 disease then OR based on Rustin criteria is a 50% decrease in serum CA125 level from two initially elevated samples confirmed by a 4th sample. (NCT00520013)
Timeframe: Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year.

Interventionproportion of patients (Number)
Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab0.65
Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib.60

[back to top]

Consolidation Progression-Free Survival

Consolidation PFS based on the Kaplan-Meier method was defined as the time from the first day of consolidation therapy to documented disease progression (PD) or disease-specific death. Based on RECIST 1.1, radiographic PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum since beginning consolidation, the appearence of one or more new lesions and/or unequivocal progression of existing non-target lesions. Based on Rustin criteria, serlogic PD was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to >/= 2xULN with either event documented on 2 occasions. Patients who were event-free were censored at the date of their last disease evaluation. (NCT00520013)
Timeframe: Assessments occurred every cycle (serologic) and every 3 cycles (radiologic) on consolidation treatment. Pts were allowed on consolidation therapy for up to 1 year and upon treatment discontinuation were followed for another year.

Interventionmonths (Median)
Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab13.3
Carboplatin/Paclitaxel/Bevacizumab Then Bevacizumab/Erlotinib18.9

[back to top]

Duration of Response

The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR=disappearance of all target lesions; PR=at least a 30% decrease in sum of longest diameter of target lesions. (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 3 or 4 toxicity) have been observed (up to 33.3 months).

Interventionmonths (Median)
Pemetrexed Plus Carboplatin5.5
Docetaxel Plus Carboplatin5.4

[back to top]

Percentage of Participants With Tumor Response (Response Rate)

Response using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR)=disappearance of all target lesions; Partial Response (PR)=at least a 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD)=at least a 20% increase in sum of longest diameter of target lesions; Stable Disease (SD)=small changes not meeting above criteria. Response rate (%)=Number of participants with CR+PR/Number of participants analyzed *100. Disease Control rate=Number of participants with SD+PR+CR/Number of participants analyzed *100. (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 3 or 4 toxicity) have been observed (up to 33.3 months).

,
Interventionpercentage of participants (Number)
Tumor Response RateDisease Control RateComplete ResponsePartial ResponseStable DiseaseProgressive DiseaseUnknown
Docetaxel Plus Carboplatin23.164.4023.141.317.318.3
Pemetrexed Plus Carboplatin34.074.50.933.040.616.09.4

[back to top]

Number of Participants With Adverse Events (AEs)

Summaries of serious AEs (SAEs) and all other non-serious AEs are located in the Reported Adverse Event Module. (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 3 or 4 toxicity) have been observed (up to 33.3 months).

,
Interventionparticipants (Number)
Non-Serious Adverse Events (AEs)Serious Adverse Events (SAEs)
Docetaxel Plus Carboplatin10035
Pemetrexed Plus Carboplatin9428

[back to top]

Survival Without Grade 4 Toxicity

Survival without Grade 4 toxicity is the time from the date of randomization to the first date of a Grade 4 TEAE or death due to any cause. Participants who are alive without experiencing Grade 4 toxicity will be censored for this analysis at the date of last contact. (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 4 toxicity) have been observed (up to 33.3 months).

Interventionparticipants (Median)
Pemetrexed Plus Carboplatin12.2
Docetaxel Plus Carboplatin2.0

[back to top]

Survival Without Grade 3 or 4 Toxicity

"Defined as the time from date of randomization to first date of a Grade 3 or 4 treatment-emergent adverse event (TEAE; as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events [CTCAE], version 3.0) or death due to any cause. Grade 3 TEAE: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated. Grade 4 TEAE: Life-threatening consequences; urgent intervention indicated.~Participants who were alive without experiencing Grade 3 or 4 toxicity were censored at the date of last contact." (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 3 or 4 toxicity) have been observed (up to 33.3 months).

Interventionmonths (Median)
Pemetrexed Plus Carboplatin3.2
Docetaxel Plus Carboplatin0.7

[back to top]

Survival Without Clinically Important Grade 3 or 4 Toxicity

Survival without Grade 3 or 4 toxicity is the time from date of randomization to the first date of the following clinically important Grade 3 or 4 TEAEs graded by the Common Terminology Criteria for Adverse Events [CTCAE], version 3.0: neutropenia (lasting >5 days), febrile neutropenia, documented infections related to neutropenia, anemia, thrombocytopenia, fatigue, nausea, vomiting, diarrhea, stomatitis, and neurosensory events; or death due to any cause. Participants who were alive without experiencing Grade 3 or 4 toxicity were censored for this analysis at the date of last contact. (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 3 or 4 toxicity) have been observed (up to 33.3 months).

Interventionmonths (Median)
Pemetrexed Plus Carboplatin3.6
Docetaxel Plus Carboplatin1.3

[back to top]

Overall Survival (OS)

OS is the duration from enrollment to death. For participants who are alive, OS is censored at the last contact. (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 3 or 4 toxicity) have been observed (up to 33.3 months).

Interventionmonths (Median)
Pemetrexed Plus Carboplatin14.9
Docetaxel Plus Carboplatin14.7

[back to top]

Progression-free Survival (PFS)

Defined as the time from date of first dose to the first observation of disease progression (PD), or death due to any cause. (NCT00520676)
Timeframe: Baseline to until 218 events (defined as death or Grade 3 or 4 toxicity) have been observed (up to 33.3 months).

Interventionmonths (Median)
Pemetrexed Plus Carboplatin5.8
Docetaxel Plus Carboplatin6.0

[back to top]

Number of Patients Experiencing Congestive Heart Failure

Clinical congestive heart failure (CHF) was assessed using Left Ventricular Ejection Fraction (LVEF) and symptom information via the Cardiac Toxicity Form as well as symptom information collected via the Adverse Event Form. Clinical CHF was defined as symptomatic decline in LVEF to below the lower limit of normal (LLN) or symptomatic diastolic dysfunction. (NCT00520975)
Timeframe: assessed every 3 months while on treatment and at 3 months post treatment

Interventionparticipants (Number)
Arm A (Chemotherapy and Placebo)1
Arm B (Chemotherapy and Bevacizumab)4

[back to top]

Change in Level of Experiencing Side Effects Between Baseline and Cycle 6 Induction

Participants indicated their level of experiencing side effects across 1 item (Functional Assessment of Cancer Therapy [FACT] item G5) on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient, ranged from 0 to 4 with a higher score representing better quality of life (QOL). (NCT00520975)
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapy

Interventionscores on a scale (Median)
Arm A (Chemotherapy and Placebo)0
Arm B (Chemotherapy and Bevacizumab)1

[back to top]

Change in Neurotoxicity Level Between Baseline and Cycle 6 Induction

Participants indicated their level of neurotoxicity symptoms across 4 items using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) scale, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient ranged from 0 to 16 with higher scores representing fewer neurotoxic symptoms. (NCT00520975)
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapy

Interventionscores on a scale (Median)
Arm A (Chemotherapy and Placebo)2
Arm B (Chemotherapy and Bevacizumab)3

[back to top]

Change in Fatigue Level Between Baseline and Cycle 6 Induction

Fatigue level was measured using Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue subscale. Participants indicated their level of fatigue across 13 items, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient was calculated by taking the reverse of each item (unless specified not to), taking the sum of those items, multiplying the sum by the number of items in the scale, and then dividing that number by the number of answered items. Total score ranged from 0 to 52 with higher scores representing less fatigue. (NCT00520975)
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapy

Interventionscores on a scale (Median)
Arm A (Chemotherapy and Placebo)2.0
Arm B (Chemotherapy and Bevacizumab)3.0

[back to top]

Change in FACT/NCCN Breast Symptom Index (FBSI) Between Baseline and Cycle 6 Induction

Participants indicated their level of breast symptoms across 8 items using the Functional Assessment of Cancer Therapy/National Comprehensive Cancer Network (FACT/NCCN) FBSI scale, each item on a 5-point Likert scale ranging from 0 (not at all) to 4(very much). Total score per patient, ranged from 0 to 32 with higher scores representing fewer symptoms. (NCT00520975)
Timeframe: assessed at baseline and at cycle 6 induction prior to starting maintenance therapy

Interventionscores on a scale (Median)
Arm A (Chemotherapy and Placebo)1
Arm B (Chemotherapy and Bevacizumab)2

[back to top]

Progression-free Survival

Progression-free survival (PFS) was defined as time from date of randomization to first disease progression, new second breast primaries, or to death from any cause, whichever occurred first, otherwise cases were censored at date last documented to be free of progression. Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier method was used to estimate the median PFS. (NCT00520975)
Timeframe: assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 years

InterventionMonths (Median)
Arm A (Chemotherapy and Placebo)11.1
Arm B (Chemotherapy and Bevacizumab)13.8

[back to top]

Number of Circulating Tumor Cells at Baseline

Number of circulating tumor cells per 7.5mL blood were counted prior to starting protocol therapy (NCT00520975)
Timeframe: assessed at baseline prior to starting protocol therapy

Interventionnumber of cells per 7.5 mL blood (Median)
Arm A (Chemotherapy and Placebo)4
Arm B (Chemotherapy and Bevacizumab)2

[back to top]

Overall Response Rate

Overall response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all randomized patients. Responses are evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and/or persistence of one or more non-target lesion(s). (NCT00520975)
Timeframe: assessed at baseline, every 12 weeks while on treatment, then very 3 months if patient is <2 years from study entry, every 6 months if 2-5 years from study entry, and annually if 6-10 years from study entry until disease progression

Interventionproportion of participants (Number)
Arm A (Chemotherapy and Placebo)0.542
Arm B (Chemotherapy and Bevacizumab)0.604

[back to top]

Overall Survival

Overall survival (OS) is defined as the time from randomization until death (event), or censored at last date known alive. Kaplan-Meier method was used to estimate the median OS. (NCT00520975)
Timeframe: assessed every 3 months for patients within 2 years of registration, every 6 months for patients 3-5 years from registration and then yearly for up to10 years

InterventionMonths (Median)
Arm A (Chemotherapy and Placebo)49.1
Arm B (Chemotherapy and Bevacizumab)63.0

[back to top]

Proportion of Progression-free at 6 Months

Disease progression was defined using the Response Evaluation Criteria in Solid Tumours (RECIST) version 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Proportion of progression-free at 6 months was calculated using the Kaplan-Meier method. (NCT00520975)
Timeframe: assessed at baseline, at 3 and 6 months after study entry

Interventionproportion of participants (Number)
Arm A (Chemotherapy and Placebo)0.826
Arm B (Chemotherapy and Bevacizumab)0.871

[back to top]

Selenium Level by Incidence of SAE

Median Selenium level by Incidence of SAE. Mann-Whitney-Wilcoxon test was used to test the correlation between selenium levels and serious adverse events. (NCT00526890)
Timeframe: Pre-treatment and every week for 6 weeks prior to chemotherapy.

Interventionng/mL (Median)
No SAESAE
CPSR1435.01803.6

[back to top]

Response Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00526890)
Timeframe: 1 month post-treatment, then q 3 months x 4

Interventionpercentage of patients (Number)
CPSR50

[back to top]

Overall Survival

(NCT00526890)
Timeframe: Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter

Interventionmonths (Median)
CPSR14.5

[back to top]

Incidence of Grade 3-4 Pneumonitis

(NCT00526890)
Timeframe: During study treatment, up to 6 weeks

Interventionpercentage of participants (Number)
CPSR0

[back to top]

Failure-free Survival

(NCT00526890)
Timeframe: Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter.

Interventionmonths (Median)
CPSR9.0

[back to top]

Incidence of Grade 3-4 Myelosuppression

(NCT00526890)
Timeframe: During study treatment, up to 6 weeks

Interventionpercentage of participants (Number)
CPSR12.50

[back to top]

Incidence of Grade 3-4 Esophagitis

(NCT00526890)
Timeframe: During study treatment, up to 6 weeks

Interventionpercentage of participants (Number)
CPSR18.75

[back to top]

Overall Survival in Participants With NSCLC

Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive. (NCT00527735)
Timeframe: Randomization date to date of death (of censored, maximum reached: 26.5 months)

InterventionMonths (Median)
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)9.69
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)12.22
Placebo + Paclitaxel/Carboplatin8.28

[back to top]

Overall Survival in Participants With SCLC

Overall Survival is defined as the time from the date of randomization until the date of death. For participants who have not died, Overall Survival was censored at the recorded last date of contact; participants with a missing recorded last date of contact were censored at the last date the participant was known to be alive. (NCT00527735)
Timeframe: Randomization date to date of death (of censored, maximum reached: 22 months)

InterventionMonths (Median)
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)3.89
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)5.22
Placebo + Paclitaxel/Carboplatin5.19

[back to top]

Progression-free Survival (PFS) in Participants With SCLC Per mWHO Criteria

By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. (NCT00527735)
Timeframe: Randomization date to date of progression or death (of censored, maximum reached: 22 months)

InterventionMonths (Mean)
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)3.89
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)5.22
Placebo + Paclitaxel/Carboplatin5.19

[back to top]

Best Overall Response Rate (BORR) Per mWHO Criteria in Participants With NSCLC and SCLC

mWHO criteria define BORR as the number of patients with best overall response of Complete Response (CR) or Partial Response (PR), divided by the total number of participants in the data set (multiplied by 100 for percentage). CR=Complete disappearance of all index lesions; PR=decrease from baseline of >=50% in the sum of products of the 2 largest perpendicular diameters of all index lesions. Independent review committee performed tumor assessment. (NCT00527735)
Timeframe: Tumor assessment at screening, every 6 weeks on treatment to Week 24, and every 12 weeks on maintenance

,,
InterventionPercentage of participants (Number)
BORR (mWHO criteria) NSCLC cohort (n=70, 68, 66)BORR (mWHO criteria) SCLC cohort (n=43, 42, 45)
Ipilimumab + Paclitaxel/Carboplatin (Sequential)32.457.1
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)21.432.6
Placebo + Paclitaxel/Carboplatin13.648.9

[back to top] [back to top] [back to top] [back to top]

Number of Participants With NSCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings

Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area. (NCT00527735)
Timeframe: At screening; Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent

,,
InterventionParticipants (Number)
Vital sign measurementsPhysical examination findings
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)00
Placebo + Paclitaxel/Carboplatin00
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)00

[back to top]

Number of Participants With NSCLC Who Have Abnormalities in On-Study Liver Function Test Results By Worst CTC Grade

ULN=Upper limit of normal among all laboratory ranges. ALT=alanine transaminase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN. (NCT00527735)
Timeframe: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent

,,
InterventionParticipants (Number)
Alanine aminotransferase (ALT), Grade 1ALT, Grade 2ALT, Grades 3 and 4Aspartate aminotransferase (AST), Grade 1AST, Grade 2AST, Grades 3 and 4Total bilirubin, Grade 1Total bilirubin, Grade 2Total bilirubin, Grades 3 and 4Alkaline phosphatase, Grade 1Alkaline phosphatase, Grade 2Alkaline phosphatase, Grades 3 and 4
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)242116011302410
Placebo + Paclitaxel/Carboplatin193120012102431
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)154118213202821

[back to top]

Progression-free Survival (PFS) in Participants With NSCLC Per Modified World Health Organization (mWHO) Criteria

By mWHO criteria, PFS is defined as the time between the randomization date and the date of progression or death, whichever occurs first. For participants with no recorded postbaseline tumor assessment, PFS was censored at the day of randomization. A participant who died without reported prior progression was considered to have progressed on the date of death. For those who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. Independent review committee performed tumor assessment. (NCT00527735)
Timeframe: Randomization date to date of progression or death (of censored, maximum reached: 13.6 months)

InterventionMonths (Mean)
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)4.11
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)5.13
Placebo + Paclitaxel/Carboplatin4.21

[back to top]

Number of Participants With SCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade

CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Gr 1:NCT00527735)
Timeframe: At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment

,,
InterventionParticipants (Number)
White blood cells, Grade 1 (n=39, 42, 43)White blood cells, Grade 2 (n= 39, 42, 43)White blood cells, Grades 3 (n= 39, 42, 43)White blood cells, Grade 4 (n= 39, 42, 43)Absolute neutrophil count, Grade 1 (n= 39, 42, 43)Absolute neutrophil count, Grade 2 (n= 39, 42, 43)Absolute neutrophil count, Grade 3 (n= 39, 42, 43)Absolute neutrophil count, Grade 4 (n= 39, 42, 43)Platelet count, Grade 1 (n= 39, 42, 43)Platelet count, Grade 2 (n= 39, 42, 43)Platelet count, Grade 3 (n= 39, 42, 43)Platelet count, Grade 4 (n= 39, 42, 43)Hemoglobin, Grade 1 (n= 39, 42, 43)Hemoglobin, Grade 2 (n= 39, 42, 43)Hemoglobin, Grade 3 (n= 39, 42, 43)Hemoglobin, Grade 4 (n= 39, 42, 43)
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)7100088211521026820
Placebo + Paclitaxel/Carboplatin137008911023310251130
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)11920892218321241022

[back to top]

Number of Participants With SCLC Who Have Positive HAHA Status Postbaseline

An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline. (NCT00527735)
Timeframe: Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

,
InterventionParticipants (Number)
Positive at any timepoint (n=42, 42)Positive postbaseline (n=38, 41)
Ipilimumab + Paclitaxel/Carboplatin (Sequential)30
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)22

[back to top] [back to top] [back to top] [back to top]

Percentage of Participants With NSCLC Who Have Abnormalities in On-study Hematology Laboratory Test Results by Worst CTC Grade

CTC, Version 3 used to assess parameters. LLN=lower limit of normal. CTC criteria: ANC=absolute neutrophil count. White blood cells Grade (Gr) 1:NCT00527735)
Timeframe: At screening; predose Day 1; and Weeks 4, 7, 10, 13, 16, 19, and 24; and every 12 weeks on maintenance until disease progression, study closure, or withdrawal of consent

,,
InterventionPercentage of participants (Number)
White blood cell count, Grades 3 and 4Hemoglobin, Any gradeHemoglobin, Grades 3 and 4ANC, Grades 3 and 4Platelets, Grades 3 and 4
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)7.790.810.87.71.5
Placebo + Paclitaxel/Carboplatin3.290.26.39.59.5
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)6.298.56.21.53.1

[back to top]

Percentage of Participants With NSCLC Who Have Abnormalities in Pancreatic Enzyme Clinical Laboratory Test Results by Worst CTC Grade

ULN=upper limit of normal. Lipase (U/L) Gr 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Grade 2 >1.5 to 2.0*ULN, Grade 3 >2.0 to 5.0*ULN, Grade 4 >5.0*ULN. Creatine (mg/dL) Grade 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN. (NCT00527735)
Timeframe: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

,,
InterventionPercentage of participants (Number)
Lipase, Grades 3 and 4Amylase, Grades 3 and 4
Ipilimumab + Paclitaxel/Carboplatin (Sequential)6.24.6
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)7.71.5
Placebo + Paclitaxel/Carboplatin3.21.6

[back to top]

Percentage of Participants With SCLC Who Have Abnormalities in Pancreatic Enzyme and Other Clinical Laboratory Test Results by Worst CTC Grade

ULN=upper limit of normal. Lipase (U/L) Grade (Gr) 1: 1.1 to 1.39*ULN; Gr 2: >1.5 to 2.0*ULN; Gr 3: 2.5 to 5; Gr 4: 5*ULN. Amylase (U/L) Gr 1: >ULN to 1.5*ULN; Gr 2 >1.5 to 2.0*ULN, Gr 3 >2.0 to 5.0*ULN, Gr 4 >5.0*ULN. Creatine (mg/dL) Gr 1: >ULN to 1.5*ULN, Gr 2: 1.5 to 3.0*ULN, Gr 3: >3.0 to 6.0*ULN, Gr 4: >6.0*ULN. (NCT00527735)
Timeframe: At screening, predose Day 1, and Weeks 4, 7, 10, 13, 16, 19, 24, and at end of treatment

,,
InterventionPercentage of participants (Number)
Lipase, Grades 3 and 4Amylase, Grades 3 and 4Creatinine, Grades 3 and 4
Ipilimumab + Paclitaxel/Carboplatin (Sequential)16.74.80
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)7.75.10
Placebo + Paclitaxel/Carboplatin11.64.70

[back to top]

irPFS in Participants With SCLC Per irRC

IRC performed TA. (NCT00527735)
Timeframe: Randomization date to date of irPD or death (maximum reached: 22 months)

InterventionMonths (Mean)
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)5.68
Ipilimumab + Paclitaxel/Carboplatin (Sequential)6.44
Placebo + Paclitaxel/Carboplatin5.26

[back to top]

Number of Participants With NSCLC Who Have Positive Human Antihuman Antibody (HAHA) Status Postbaseline

An electrochemilumiluminescent immunoassay was used to detect HAHA antibodies to ipilimumab in human serum. Baseline, either negative or positive, is the maximum of all measurements closest and prior to the first ipilimumab dose. Positive status postbaseline=participants with an increase in HAHA measurement from baseline. (NCT00527735)
Timeframe: Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

InterventionParticipants (Number)
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)2
Ipilimumab + Paclitaxel/Carboplatin (Sequential)1

[back to top]

Number of Participants With SCLC Who Had Abnormalities in Vital Sign Measurements and Physical Examination Findings

Vital signs measurements consisted of systolic and diastolic blood pressure, heart rate, temperature, and respiratory rate. Physical examinations assessed weight, height, performance status, and body surface area. (NCT00527735)
Timeframe: Predose Day 1; Weeks 4, 7, 10, 13, 16, and 24; and every 12 weeks on maintenance until end of treatment

,,
InterventionParticipants (Number)
Vital sign measurementsPhysical examination findings
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)00
Placebo + Paclitaxel/Carboplatin00
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)00

[back to top]

Number of Participants With SCLC Who Have Abnormalities in Liver Function Test Results by Worst CTC Grade

ALT=alanine aminotransferase; AST=aspartate aminotransferase; ALK=alkaline phosphatase. ULN=Upper limit of normal among all laboratory ranges. CTC grade criteria: ALT Grade 1:>ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. AST Grade 1: >ULN to 2.5*ULN; Grade 2: >2.5 to 5.0*ULN; Grade 3: >5.0 to 20.0*ULN; Grade 4: >20.0*ULN. Total bilirubin Grade 1: >ULN to 1.5*ULN; Grade 2: >1.5 to 3.0*ULN; Grade 3: >3.0 to 10.0*ULN; Grade 4: >10.0*ULN. ALK (U/L) G1:>ULN to 2.5*ULN, G2:>2.5 to 5.0*ULN, G3:>5.0 to 20.0*ULN, G4:>20.0*ULN. (NCT00527735)
Timeframe: At screening; predose Day 1; Weeks 4, 7, 10, 13, 16, 19, and 24; and at end of treatment

,,
InterventionParticipants (Number)
ALT, Grade 1ALT, Grade 2ALT, Grades 3 & 4AST, Grade 1AST, Grade 2AST, Grades 3 & 4Total bilirubin, Grade 1Total bilirubin, Grade 2Total bilirubin, Grades 3 & 4ALK, Grade 1ALK, Grade 2ALK, Grades 3 & 4
Ipilimumab/Placebo + Paclitaxil/Carboplatin (Concurrent)122711454111510
Placebo + Paclitaxel/Carboplatin81012203001620
Placebo/Ipilimumab + Paclitaxel/Carboplatin (Sequential)123213135001430

[back to top]

Time to Progressive Disease (TTPD)

TTPD was defined as the time from the date of randomization until the first date of objectively determined progressive disease (PD). For participants who died without objective PD (including death from study disease), TTPD was censored at the date of the last objective progression-free disease assessment. For participants not known to have died as of the data cutoff and did not have PD, TTPD was censored at the date of the last objective progression-free disease assessment. (NCT00533429)
Timeframe: Randomization to measured PD or death from any cause up to 12.2 months

InterventionMonths (Median)
Enzastaurin + Pemetrexed + Carboplatin + Bevacizumab4.3
Pemetrexed + Carboplatin + Bevacizumab + Placebo4.8

[back to top]

Progression-Free Survival (PFS)

PFS was defined as the time from date of randomization to the first observation of progressive disease (PD) or death due to any cause. For participants not known to have died as of the data cutoff date and who did not have objective PD, PFS was censored at the date of the last objective progression-free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to objective disease progression or death, PFS was censored at the date of the last objective progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. (NCT00533429)
Timeframe: Randomization to measured PD or death from any cause up to 12.2 months

Interventionmonths (Number)
Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin3.5
Pemetrexed + Carboplatin + Bevacizumab + Placebo4.3

[back to top]

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Response Rate)

"Tumor response rate was defined as number of participants with overall best response of CR or PR over number of protocol qualified participants using the Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all tumor lesions. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum of LDs or complete disappearance of target lesions, with persistence (but not worsening) of 1 or more non-target lesions. In either case, no new lesions may have appeared.~Percentage of participants was calculated as: (number of participants with CR or PR/ number of participants qualified for tumor response analysis) × 100." (NCT00533429)
Timeframe: Randomization to measured progressive disease or death from any cause up to 12.2 months

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin20.0
Pemetrexed + Carboplatin + Bevacizumab + Placebo30.0

[back to top]

Overall Survival (OS)

OS was defined as the time from the date of randomization to the date of death from any cause. For participants who were not known to have died as of the data cutoff, OS was censored at the last contact date. (NCT00533429)
Timeframe: Randomization to date of death up to 14.3 months

Interventionmonths (Median)
Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin9.1
Pemetrexed + Carboplatin + Bevacizumab + Placebo7.6

[back to top]

Duration of Response (DoR)

The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression or death from any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST v1.0) criteria. CR was defined as the disappearance of all target lesions and PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions taking as reference the baseline sum of LDs. For participants who died without progressive disease or who were alive, DoR was censored at the last contact of progression free assessment. For participants who received subsequent anticancer therapy (after discontinuation from all study treatment) prior to PD, DoR was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation anticancer therapy. Due to early study closure, DoR was not analyzed. (NCT00533429)
Timeframe: Time of response to disease progression or death from any cause up to 12.2 months

InterventionMonths (Median)
Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin4.7
Pemetrexed + Carboplatin + Bevacizumab + Placebo3.5

[back to top]

Pharmacology Toxicity and Adverse Events (AEs)

Clinically significant events were defined as serious AEs (SAEs) and other non-serious AEs. Participants who died due to progressive disease (PD) or an AE while on treatment and or died during the 30 day post-treatment follow-up are included. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. (NCT00533429)
Timeframe: Randomization up to 14.3 months and 30-day follow-up

,
InterventionParticipants (Count of Participants)
Non-serious AEsSerious AEsDeaths Due to PDDeaths Due to AEsDeaths within 30-days after treatment
Pemetrexed + Carboplatin + Bevacizumab + Enzastaurin196010
Pemetrexed + Carboplatin + Bevacizumab + Placebo207010

[back to top]

Percentage of Patients With Decline From Baseline to 3 Months in the Lung Cancer Subscale (LCS) of the Functional Assessment of the Cancer Therapy Trial Outcome Index (FACT-TOI).

A decline of 2 points in the LCS from baseline to 3 months was considered a clinically meaningful change indicating a decline in quality of life. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy. (NCT00533949)
Timeframe: At baseline and 3 months.

Interventionpercentage of participants (Number)
Combined Patients Receiving 60 Gy RT29.9
Combined Patients Receiving 74 Gy RT45.0

[back to top]

Local-regional Failure (Reported as Two-year Estimates)

A failure for local-regional failure is the first occurrence of local or regional progression. Time is measured from the date of randomization to the date of first failure. Patients alive without local or regional failure at the time of last follow-up are censored. Patients who died without local or regional failure are considered as having competing risk at the time of death. Local-regional failure was estimated by the cumulative incidence method and 2 year estimates are reported. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

Interventionpercentage of participants (Number)
Combined Patients Receiving 60 Gy RT42.3
Combined Patients Receiving 74 Gy RT48.4
Combined Patients Receiving Cetuximab47.1
Combined Patients From Arms Receiving No Cetuximab40.7

[back to top]

Prognostic Value of Pre-treatment Standardized Uptake Value (SUV) of Positron Emission Tomography (PET) Scan in Predicting Survival, Distant Metastasis, and Local-regional Failure

Standardized uptake value (SUV) is a simple way of determining activity in PET imaging. It is a mathematically derived ratio of tissue radioactivity concentration at a point in time and the injected dose of radioactivity per kilogram of the patient's body weight. All event times are time from randomization to date of event or censoring. A survival event is death from any cause, patients without events are censored at the date of last contact, and survival rates are estimated by Kaplan-Meier method. Local-regional and distant metastasis events are the first development of progressive disease locally/regionally or distant metastasis, respectively, patients who do not have an event are censored at the date of death or last contact, and event rates are estimated by cumulative incidence. Two-year rates are presented. PET SUV was evaluated as a continuous variable therefore the outcome variables are not summarized by PET SUV. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

Interventionpercentage of participants (Number)
Overall SurvivalTime to Distant MetastasisTime to Local-Regional Failure
All Patients50.546.743.7

[back to top]

Percentage of Participants With Grade 3-5 Esophagitis and Pneumonitis Adverse Events as Assessed by NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v3.0

Treatment-related esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

,
Interventionpercentage of participants (Number)
EsophagitisPneumonitis
Combined Patients Receiving 60 Gy RT7.46.9
Combined Patients Receiving 74 Gy RT20.84.3

[back to top]

Overall Survival and Local-regional Failure by Epithelial Growth Factor Receptor (EGFR) Group

EGFR is a protein that is present on the surface of both normal cells and cancer cancer cells. EGFR H-Score is a measure of staining intensity ranging from 0 to 300 where a higher value indicates greater intensity of EGFR. Available tumor samples were evaluated for EGFR and given an H-Score. Patients were divided into two groups based on H-Score values dichotomized at 200. All event times are time from randomization to date of event or censoring. A survival event is death from any cause, patients without events are censored at the date of last contact, and survival rates are estimated by Kaplan-Meier method. A local-regional event is the first development of progressive disease locally or regionally, patients who do not have an event are censored at the date of death or last contact, and event rates are estimated by cumulative incidence. Two-year rates are reported. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

,
Interventionpercentage of participants (Number)
Two-year Survival rateTwo-year Local-regional Failure rate
EGFR H-Score < 20051.737.4
EGFR H-Score >= 20052.847.2

[back to top]

Progression-free Survival

A failure for progression-free survival (PFS) is the first occurrence of local or regional progression, distant metastases, or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Time is measured from the date of randomization to the date of first failure. Patients without failure are censored at the date of last follow-up. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

Interventionmonths (Median)
Combined Patients Receiving 60 Gy RT11.8
Combined Patients Receiving 74 Gy RT9.8
Combined Patients Receiving Cetuximab10.8
Combined Patients From Arms Receiving No Cetuximab10.7

[back to top]

Prognostic and Predictive Effects of Gross Tumor Volume (GTV) on Overall Survival

"Gross tumor volume (GTV) is defined as the combined volume (cubic centimeters) of the primary tumor and clinically positive lymph nodes seen either on the planning computed tomography (CT) scan or the pretreatment positron emission tomography (PET) scan. Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. GTV was evaluated as a continuous variable therefore overall survival time is not summarized by GTV. Prognostic refers to the main effect and predictive refers to the interaction between GTV and treatment arm." (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

Interventionmonths (Median)
All Patients25.0

[back to top]

Percentage of Patients With Grade 3+ Adverse Events by Epithelial Growth Factor Receptor (EGFR) Group

EGFR is a protein that is present on the surface of both normal cells and cancer cancer cells. EGFR H-Score is a measure of staining intensity ranging from 0 to 300 where a higher value indicates greater intensity of EGFR. Available tumor samples were evaluated for EGFR and given an H-Score. Patients were divided into two groups based on H-Score values dichotomized at 200. Worst toxicity as determined by adverse events was used as a measure of a patient's quality of life (QOL). Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to AE. Highest grade (worst) adverse event (AE) per subject was counted. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

Interventionpercentage of participants (Number)
EGFR H-Score < 20072.1
EGFR H-Score >= 20085.3

[back to top]

Percentage of Participants With Other Grade 3-5 Adverse Events as Assessed by NCI CTCAE v3.0

Treatment-related adverse events other than esophagitis and pneumonitis were assessed graded using the CTCAE v3.0. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

Interventionpercentage of participants (Number)
Combined Patients Receiving 60 Gy RT75.1
Combined Patients Receiving 74 Gy RT77.8

[back to top]

Patient-reported Swallowing Score (Area Under the Curve)

Patients completed a swallowing diary prior to the start of treatment and then daily during treatment. Patients recorded a score to indicate problems with swallowing on that day (1-None, 2-Mild soreness only, 3-Can swallow solids with some difficulty, 4-Cannot swallow solids, 5-Cannot swallow liquids). These scores were then plotted across time and the area under the curve from baseline until the end of week 6 was calculated. A lower area under the curve indicates better swallowing ability. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation therapy. (NCT00533949)
Timeframe: From randomization to 6 weeks after start of radiation therapy (6-10 weeks from randomization)

InterventionArea under curve (score * days) (Median)
Combined Patients Receiving 60 Gy RT79.5
Combined Patients Receiving 74 Gy RT78.0

[back to top]

Overall Survival

Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (NCT00533949)
Timeframe: From randomization to last follow-up. Analysis occured after all patients were on study for 18 months. Maximum follow-up at time of analysis was 61.5 months.

Interventionmonths (Median)
Combined Patients Receiving 60 Gy RT28.7
Combined Patients Receiving 74 Gy RT20.3
Combined Patients Receiving Cetuximab25.0
Combined Patients From Arms Receiving No Cetuximab24.0

[back to top]

EuroQoL (EQ5D) Visual Analog Scale (VAS) Through One Year (Area Under the Curve)

The visual analogue scale is a self-assessment of current health state, measured on a 20-cm scale ranging from 0 for the worst imaginable health state to 100 for best imaginable health state, marked at 10-point intervals. The area under the curve of each subject's EQ5D visual analog scale (VAS) response trajectory within 1 year was calculated. The EQ5D VAS utility was normalized by the baseline score. The trajectory included all available time points through one year. If a subject died within one year, the EQ5D VAS was reduced to 0 at the time of death. If subject was censored within one year, the EQ5D utility curve was truncated at the time of censoring. The scores were plotted across time and the area under the curve was calculated. A greater area under the curve indicates a better health state. Comparisons are only made between radiation therapy dosing levels because the cetuximab regimen was known to be safe in combination with radiation (NCT00533949)
Timeframe: From randomization to one year

InterventionScore on a scale * months (Median)
Combined Patients Receiving 60 Gy RT279.5
Combined Patients Receiving 74 Gy RT265.4

[back to top]

Death During or Within 30 Days of Discontinuation of Protocol Treatment

Deaths regardless of cause and occuring during or within 30 days of discontinuation of protocol treatment were evaluated. (NCT00533949)
Timeframe: From start of protocol treatment to 24 months.

Interventionpercentage of participants (Number)
60 Gy RT2
74 Gy RT3.8
60 Gy RT + Cetuximab8.8
74 Gy RT + Cetuximab4.1

[back to top]

Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)

Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed. (NCT00536601)
Timeframe: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years

InterventionProportion of participants (Number)
BuCy
Acute Leukemia33

[back to top]

Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)

Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed. (NCT00536601)
Timeframe: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years

InterventionProportion of participants (Number)
VCpCyTtCpTtC1500
Solid Tumors43050

[back to top]

Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)

Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed. (NCT00536601)
Timeframe: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years

InterventionProportion of participants (Number)
BuCyCBVVCp
Non-Hodgkin Lymphoma22370

[back to top]

Response Rate (Complete Remission)

Response rates will be reported using descriptive statistics. (NCT00536601)
Timeframe: At 100 days

InterventionParticipants (Count of Participants)
Acute Leukemia5
Hodgkin Lymphoma17
Non-Hodgkin Lymphoma54
MM/Amyloid17
Solid Tumors7

[back to top]

Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)

Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed. (NCT00536601)
Timeframe: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years

InterventionProportion of participants (Number)
Mel120Mel200
MM/Amyloid2213

[back to top]

Progression-free Survival (PFS) Distribution of Patients With HL, NHL, and MM for Each Disease-specific High-dose Therapy Regimen, Estimate Provided for 10-yr PFS (Median Follow-up Time in Survivors)

Assessed using the product-limit based Kaplan Meier method. Additionally, a 95% confidence interval of the distribution will be computed. (NCT00536601)
Timeframe: From the date of transplantation to the date of first observed disease progression or death due to any cause, assessed up to 12 years

InterventionProportion of participants (Number)
BuCyCBV
Hodgkin Lymphoma1443

[back to top] [back to top]

Overall Survival, Presented as the Estimate at 10-yrs (Median Follow-up Time in Survivors)

Assessed using the product-limit based Kaplan Meier method. (NCT00536601)
Timeframe: Patients are followed up to maximum of 12 years

InterventionProportion of participants (Number)
Acute Leukemia33
Hodgkin Lymphoma61
Non-Hodgkin Lymphoma45
MM/Amyloid39
Solid Tumors46

[back to top]

Engraftment Failure Rate

Engraftment Failure Rate is number of participants with engraftment failure out of total participants. Engraftment failure is defined as failure to achieve an absolute neutrophil count (ANC) >500/ul by day 42, and has no evidence of donor chimerism on bone marrow examination. (NCT00539500)
Timeframe: Participant evaluation at Day 42, total study up to 3 Years

InterventionParticipant (Number)
Transplantation CD133+ Cells0

[back to top]

Number of Treated Participants With Engraftment Failure at Day 42

Engraftment failure is defined as if by day +42 participant does not have an absolute neutrophil count (ANC) >500/ul, and has no evidence of donor chimerism on bone marrow examination. (NCT00539500)
Timeframe: Participant evaluation at Day 42

Interventionparticipants (Number)
Transplantation CD133+ Cells0

[back to top] [back to top]

Progression-free Survival by Blinded Radiology Assessment

"Progression free survival time was defined as the time from the day of randomization to the start of disease progression or death (any cause), whichever occurred first, based on the blinded radiological review response assessment. Progressive disease was defined as a ≥ 20% increase in the SLD of target lesions, taking as reference the nadir SLD recorded since the treatment started, or the presence of one or more new lesions, or the unequivocal progression of existing non-target lesion(s) or appearance of one or more new lesion(s).~Participants who did not have disease progression or had not died were censored at the last visit they were documented as progression free. If palliative radiotherapy or surgery at lesion sites occurred, the participant was censored at the last date without documented progression prior to radiotherapy or surgery. In follow-up, participants who began new therapy prior to progression were censored at the last documented date as progression-free." (NCT00540514)
Timeframe: Assessed every 6 weeks until progression or death, up to 38 months

Interventionmonths (Median)
Albumin-bound Paclitaxel + Carboplatin6.3
Paclitaxel + Carboplatin5.8

[back to top]

Percentage of Participants With Controlled Disease

Controlled disease was defined as the percentage of participants with stable disease for ≥ 16 weeks or confirmed complete or partial overall response, based on blinded radiological assessment. Stable disease was defined as neither sufficient shrinkage of target lesions to qualify for Partial Response, nor sufficient increase to qualify for Progressive Disease, or the persistence of one or more non-target lesions not qualifying for Complete Response or Progressive Disease. (NCT00540514)
Timeframe: Assessed every 6 weeks, up to 22 months

Interventionpercentage of participants (Number)
Albumin-bound Paclitaxel + Carboplatin53
Paclitaxel + Carboplatin49

[back to top]

Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment

"Antitumor response was defined as the percentage of participants who achieved an objective response (Confirmed Response [CR] or Partial Response [PR]), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0.~A complete response was defined as a disappearance of all target and non-target lesions and no new lesions.~Partial response was defined as ≥ 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, and the persistence of one or more non-target lesions not qualifying for CR or Progressive Disease (the unequivocal progression of existing non-target lesion(s) or appearance of one or more new lesions)." (NCT00540514)
Timeframe: Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.

Interventionpercentage of participants (Number)
Albumin-bound Paclitaxel + Carboplatin33
Paclitaxel + Carboplatin25

[back to top]

Duration of Response in Responding Patients

Duration of response was assessed by progression free survival for participants who achieved a confirmed complete response or partial response based on blinded radiological assessment. (NCT00540514)
Timeframe: Assessed every 6 weeks, up to 38 months

Interventionmonths (Median)
Albumin-bound Paclitaxel + Carboplatin9.6
Paclitaxel + Carboplatin9.5

[back to top]

Maximal Degree of Anemia Based on Clinical Laboratory Values for Hemoglobin

The maximal degree of anemia (and myelosuppression) was assessed by the overall nadir of hemoglobin levels based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. (NCT00540514)
Timeframe: 38 months

Interventiong/L (Mean)
Albumin-bound Paclitaxel + Carboplatin90.0
Paclitaxel + Carboplatin103.9

[back to top]

Overall Participant Survival

Overall survival was defined as the time from the day of randomization to participant death (due to any cause), as assessed by post study follow-up performed monthly for 6 months and every 3 months thereafter for 12 months. All participants who were lost to the follow-up prior to the end of the trial or who completed the 18 month follow up phase were censored at last known time the participant was alive. (NCT00540514)
Timeframe: Up to 38 months

Interventionmonths (Median)
Albumin-bound Paclitaxel + Carboplatin12.1
Paclitaxel + Carboplatin11.2

[back to top]

Maximal Degree of Neutropenia Based on Clinical Laboratory Values of Absolute Neutrophil Count

The maximal degree of neutropenia (and myelosuppression) was assessed by the overall nadir of absolute neutrophil count (ANC) based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. (NCT00540514)
Timeframe: 38 months

Intervention× 10^9/L (Mean)
Albumin-bound Paclitaxel + Carboplatin1.39
Paclitaxel + Carboplatin1.26

[back to top]

Maximal Degree of Thrombocytopenia Based on Clinical Laboratory Values of Platelet Count

The maximal degree of thrombocytopenia (and myelosuppression) was assessed by the overall nadir of platelet count based on clinical laboratory measurements graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0. (NCT00540514)
Timeframe: 38 months

Intervention× 10^9/L (Mean)
Albumin-bound Paclitaxel + Carboplatin114.9
Paclitaxel + Carboplatin136.6

[back to top] [back to top]

SPARC Status and Correlation With Overall Survival

"The expression and cellular distribution of Secreted Protein Acidic and Rich in cysteine (SPARC) in biopsies of lung tumor was examined by immunohistochemistry using a 2 antibody system by an approved central laboratory and analyzed by 2 pathologists. The following tissue components were scored: tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, and blood vessels.~To classify participants into high-SPARC and low-SPARC groups, an average z-score was calculated across variables and classified high-SPARC (average z-scores ≥0) and low-SPARC (average z-scores <0) groups.~SPARC status was then correlated with overall survival (the time from the day of randomization to participant death due to any cause)." (NCT00540514)
Timeframe: Archival tissue samples were used for SPARC analysis. Survival was assessed for up to 38 months.

,
Interventionparticipants (Number)
High-SPARCLow-SPARC
Albumin-bound Paclitaxel + Carboplatin1718
Paclitaxel + Carboplatin2214

[back to top]

Percentage of Participants Who Achieved an Objective Confirmed Complete Response or Partial Response by Blinded Radiology Assessment, by Histology

"Antitumor response was defined as the percentage of participants who achieved an objective response (Confirmed Response [CR] or Partial Response [PR]), confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. Response was based on the blinded radiological review using Response Evaluation Criteria in Solid Tumors (RECIST) response guidelines, Version 1.0.~A complete response was defined as a disappearance of all target and non-target lesions and no new lesions.~Partial response was defined as ≥ 30% decrease in the sum of the longest diameters (SLD) of target lesions, taking as reference the baseline SLD, and the persistence of one or more non-target lesions not qualifying for CR or Progressive Disease (the unequivocal progression of existing non-target lesion(s) or appearance of one or more new lesions).~Histology was determined at the time of primary diagnosis." (NCT00540514)
Timeframe: Objective response was evaluated every 6 weeks until progression or new anti-cancer therapy initiation, up to 22 months.

,
Interventionpercentage of participants (Number)
Carcinoma/Adenocarcinoma [254, 264]Squamous Cell Carcinoma [229, 221]Large Cell Carcinoma [N=9, 13]Other [N=29, 33]
Albumin-bound Paclitaxel + Carboplatin26413324
Paclitaxel + Carboplatin27241515

[back to top]

Number of Participants With Adverse Events (AEs)

A Treatment-emergent AE was any AE that began or worsened in grade after the start of study drug through 30 days after the last dose of study drug or end of study whichever is later. Treatment related toxicity was one considered by the investigator to be possibly, probably or definitely related to study drug. AEs were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v3.0 on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event (SAE) is any untoward medical occurrence at any dose that: is fatal or life-threatening; results in persistent or significant disability or incapacity; requires or prolongs in-patient hospitalization; is a congenital anomaly/birth defect in the offspring of a patient; and conditions not included in the above that may jeopardize the patient or may require intervention to prevent one of the outcomes listed above. (NCT00540514)
Timeframe: Up to 38 months

,
Interventionparticipants (Number)
At least 1 AEAt least 1 grade 3 or higher AEAt least 1 treatment-related AEAt least 1 treatment-related grade 3 or higher AEAt least 1 serious AEAt least 1 treatment-related serious AEAt least 1 AE with taxane permanently discontinuedAt least 1 AE with action of taxane dosage reducedAt least 1 AE with action of taxane interruptedAt least 1 AE with action of taxane delayed
Albumin-bound Paclitaxel + Carboplatin4833604693219337802370365
Paclitaxel + Carboplatin5043554813158030841205214

[back to top]

1) Pathologic Response

Pathologic measurement post-surgery viable primary tumor mass (NCT00542191)
Timeframe: Upon completion therapy after surgery

InterventionParticipants (Count of Participants)
Single Arm Study; Taxol, XRT, Gemzar and Carbo15

[back to top]

Response (Phase II)

Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) >=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD. (NCT00544648)
Timeframe: On-treatment date to date of progressive disease (assessed up to 2 years)

Interventionparticipants (Number)
Complete responsePartial responseStable diseaseProgressive disease
Phase II0100

[back to top]

Response (Phase I)

Number of patients in each response category, per Response Evaluation in Solid Tumors (RECIST) v.1.1: complete response (CR), disappearance of target lesions; partial response (PR) >=30% decrease in sum of longest diameter (LD) of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or PR. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD. (NCT00544648)
Timeframe: On-treatment date to date of progressive disease (assessed up to 2 years)

Interventionparticipants (Number)
Complete responsePartial responseStable diseaseProgressive disease
Phase I0910

[back to top]

Number of Patients With Each Worst Grade Toxicity (Phase II)

The number of patients with worst-grade toxicity at each of five grades following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death (NCT00544648)
Timeframe: at 16 weeks

Interventionparticipants (Number)
Number of patients with worst grade 1 toxicityNumber of patients with worst grade 2 toxicityNumber of patients with worst grade 3 toxicityNumber of patients with worst grade 4 toxicityNumber of patients with worst grade 5 toxicity
Phase II01100

[back to top]

Progression-free Survival (Phase II)

Estimated probable duration of life without disease progression, from on-study date to earlier of progression date, or date of death from any cause, using the Kaplan-Meier method with censoring (see Analysis Population Description for additional details). Disease progression is defined by Response Evaluation in Solid Tumors (RECIST) v.1.1: >= 20% increase in sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions (NCT00544648)
Timeframe: On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)

Interventiondays (Median)
Phase II126

[back to top]

Progression-free Survival (Phase I)

Estimated probable duration of life without disease progression, from on-study date to earlier of progression date, or date of death from any cause, using the Kaplan-Meier method with censoring (see Analysis Population Description for additional details). Disease progression is defined by Response Evaluation in Solid Tumors (RECIST) v.1.1: >= 20% increase in sum of the longest diameter of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions (NCT00544648)
Timeframe: On-study to lesser of date of progression or date of death from any cause (assessed up to 2 years)

Interventiondays (Median)
Phase I231

[back to top]

Overall Survival (Phase I)

Estimated probable duration of life from on-study date to date of death from any cause, using Kaplan-Meier method with censoring (see Analysis Population Description for additional details). (NCT00544648)
Timeframe: On-study date to date of death from any cause (assessed up to 2 years)

Interventiondays (Median)
Phase I575

[back to top]

Maximum Tolerated Dose of Nab-paclitaxel When Combined Concurrently With Carboplatin and Radiation (Phase I)

The highest dose in milligrams per meter of body surface squared (mg/m2) of nab-paclitaxel in combination with carboplatin while maintaining tolerability. Cohorts of 3-6 patients received escalating doses of nab-paclitaxel in combination with carboplatin until the maximum tolerated dose (MTD) was achieved. The MTD is defined as the dose preceding that at which 2 or more of 6 patients experience dose-limiting toxicity (DLT) during the initial cycle of therapy. DLTs per Common Toxicity Criteria v 3.0: recurring non-hematological (except esophagitis) > Grade 2, non-hematological or esophagitis > Grade 3 toxicities that are symptomatically unacceptable to patient and result in treatment delay for > 2 weeks, persistent toxicity resulting in treatment delay for > 2 weeks. (NCT00544648)
Timeframe: 7 weeks

Interventionmg/m2 (Number)
Phase I40

[back to top]

Number of Patients With Each Worst Grade Toxicity (Phase I)

Count of patients according to the worst-grade toxicity (WGT) experienced by each, where worst-grade toxicity is per NCI common toxicity criteria: Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening; Grade 5, death. (NCT00544648)
Timeframe: On-study date to 30 days following final dose of study drug

Interventionparticipants (Number)
Number of patients with worst Grade 1 toxicityNumber of patients with worst grade 2 toxicityNumber of patients with worst grade 3 toxicitiesNumber of patients with worst grade 4 toxicityNumber of patients with worst grade 5 toxicity
Phase I02530

[back to top]

Number of Patients With Worst-grade Toxicities Per Grade

"The intensity of the AE will be graded according to the Common Toxicity Criteria (CTC) of the (US) National Cancer Institute (NCI) - Cancer Therapy Evaluation Program (CTEP) [version 3.0 of December 2003] (Appendix B).~Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE" (NCT00550537)
Timeframe: Through study completion, an average of 1 year

Interventionparticipants (Number)
worst-grade 1worst-grade 2worst-grade 3worst-grade 4
Erlotinib Segament1851151

[back to top]

Response Rate for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC

Number of patients in each response category, per RECIST v1.1, summarized as follows for target lesion criteria (see RECIST v1.1 for additional details): complete response (CR),disappearance of target lesions; partial response (PR), >=30% decrease in sum of longest diameter of target lesions; progressive disease (PD), >=20% increase in sum of LD of target lesions or appearance of new lesions; stable disease (SD), insufficient change in target lesions or new lesions to qualify as either PD or SD. The response rate is calculated as the percentage of PR+CR among patients assessed for response. (NCT00550537)
Timeframe: Through study completion, an average of 1 year

Interventionpercentage of patients assessed (Mean)
Patients on Erlotinib Segament18.8

[back to top]

Progression-free Survival (PFS) for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC

PFS is defined as the time from on erlotinib treatment date to progression or death (whichever comes first) before cross-over to PC or PC+B. For those did not progressed nor died, they were censored at the last follow up (either the off erlotinib treatment date or lost follow up date). The median survival time and 95% confidence interval were estimated using Kaplan-meier method. (NCT00550537)
Timeframe: Through study completion, an average of 1 year

Interventionmonths (Median)
Patients on Erlotinib Segament3.16

[back to top]

Overall Survival for Erlotinib Initial Therapy in Chemotherapy-naïve Patients With Advanced NSCLC

The overall survival time is defined as the time from on treatment to death. Patients were censored of they were alive at the last follow up date. The median survival time and its confidence interval were estimated using Kaplan-meier method. (NCT00550537)
Timeframe: Through study completion, an average of 1 year

Interventionmonths (Median)
Erlotinib Followed by PC12.53
Erlotinib Followed by PC+B17.23
Erlotinib6.08

[back to top]

Response Rate

"Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:~Complete Response (CR): disappearance of all target lesions;~Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;~Progressive Disease (PD): 20% increase in sum of longest diameter of target lesions;~Stable Disease (SD): small changes that do not meet above criteria.~Response rate is reported as the percentage of participants who achieved each response." (NCT00553462)
Timeframe: Duration of study (up to 2 years)

Interventionpercentage of participants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)
Paclitaxel + Carboplatin + Radiation + Erlotinib859277

[back to top]

Progression-free Survival

Progression free survival (PFS) is defined as the time from registration to disease progression or death of any cause, which ever comes first. The median PFS with 95% CI was estimated using the Kaplan-Meier method. (NCT00553462)
Timeframe: Duration of study (up to 2 years)

Interventionmonths (Median)
Paclitaxel + Carboplatin + Radiation + Erlotinib11

[back to top]

Overall Survival at 12 Months

Percentage of participants who were alive at 12 months. (NCT00553462)
Timeframe: At 12 months

Interventionpercentage of participants (Number)
Paclitaxel + Carboplatin + Radiation + Erlotinib57

[back to top]

Response Rate to the Induction Phase of the Regimen

This study used a modified version of the international criteria for neuroblastoma response. The response rate to the induction phase of the regimen and a corresponding 95% confidence interval will be calculated for all strata combined. (NCT00554788)
Timeframe: 12 weeks after participant received the first dose

Interventionpercentage of participants (Number)
All Eligible Patients68

[back to top]

Event-free Survival (EFS)

The probability of surviving patients who did not experience events at 1 year following enrollment. An event is defined as relapse, second malignancy, or death from any cause. (NCT00554788)
Timeframe: At 1 year

InterventionProbability (Number)
Stage 2/3 Patients88
Stage 4a Patients83
Stage 4b Patients28

[back to top]

Percentage of Participants With Adverse Events as Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0

Grade 3 and higher toxicities will be descriptively summarized. (NCT00554788)
Timeframe: Up to 30 days after completion of study treatment

,,
Interventionpercentage of participants (Number)
Abdominal painAcute kidney injuryAlanine aminotransferase increasedAnemiaAnorexiaApneaAspartate aminotransferase increasedCatheter related infectionDehydrationDepressed level of consciousnessDiarrheaEncephalopathyEnterocolitisEnterocolitis infectiousEsophagitisFebrile neutropeniaFeverGGT increasedGastric hemorrhageHearing impairedHypermagnesemiaHypertensionHypoalbuminemiaHypocalcemiaHypoglycemiaHypokalemiaHypomagnesemiaHyponatremiaHypophosphatemiaHypotensionHypoxiaInfections and infestations - Other, specifyLower gastrointestinal hemorrhageLung infectionLymphocyte count decreasedMucositis oralNauseaNervous system disorders - Other, specifyNeutrophil count decreasedOral painPainPeripheral motor neuropathyPharyngeal mucositisPlatelet count decreasedPneumonitisRectal painSeizureSepsisSinus tachycardiaSinusitisSkin infectionUpper respiratory infectionVomitingWhite blood cell decreased
Stage 2/3 Patients000011.10011.1005.6005.6055.611.10011.15.6005.6027.85.611.122.20027.8016.705.616.705.6005.605.65.6000011.1011.111.15.6
Stage 4a Patients5.65.616.7033.3011.1011.1016.705.611.15.655.605.65.65.605.605.6016.75.60011.12.633.35.60027.811.1005.65.605.6005.6011.15.605.65.622.20
Stage 4b Patients005.35.315.85.35.3010.55.305.305.3036.85.3005.3005.310.55.321.110.515.810.50021.1005.35.35.310.55.300005.3005.30005.305.35.3

[back to top]

Best Tumor Response (Number of Responses Per Category) According to Response Evaluation Criteria in Solid Tumors (RECIST)

Complete response (CR): Disappearance of all target lesions (TL). Partial response (PR): At least 30% decrease in sum of the largest diameter (LD) of TLs, taking baseline sum as reference. Stable disease (SD): No change in tumor size. Progressive disease (PD): At least a 20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since treatment started, or the appearance of 1 or more new lesions. (NCT00558636)
Timeframe: Best tumor response assessed every 6 weeks by investigator during treatment up to 5 months after randomization of the first patient.

,
InterventionParticipants (Number)
Complete repsonse (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)not evaluated
Placebo + Paclitaxel + Carboplatin0028115
Sorafenib + Paclitaxel + Carboplatin0418124

[back to top] [back to top]

Overall Survival (OS)

"Overall survival is the number of days from the date of randomization to the date of death due to any cause. Subjects alive at the time of analysis were censored at their last date of follow-up. Since the study was terminated early and 89% of subjects' data were censored, only the number of subjects who Failed (died) or were Censored is reported, not the usual measure number of days." (NCT00558636)
Timeframe: Up to 5 months after randomization of the first patient

,
InterventionParticipants (Number)
Failed (died)Censored
Placebo + Paclitaxel + Carboplatin143
Sorafenib + Paclitaxel + Carboplatin443

[back to top]

Change From Baseline of Lung Cancer Symptoms (LCS) Score Assessed at Each Treatment Cycle (21 Days Per Cycle) Starting With Cycle 2

"The LCS is a validated instrument for determining treatment impact on lung symptoms. The LCS consists of 7 questions with 5 responses ranging from not at all to very much. The LCS total score ranges from 0 to 28. Lower scores reflect greater lung cancer symptoms." (NCT00558636)
Timeframe: Change from baseline of LCS score assessed at each treatment cycle starting with Cycle 2 (Cycles 2, 3, 4, 5, 6, 7; 21 days per cycle) up to 5 months after randomization of the first patient.

,
Interventionunits on a scale (Mean)
Cycle 2 (N = 31 sorafenib/33 placebo)Cycle 3 (N = 16 sorafenib/23 placebo)Cycle 4 (N = 12 sorafenib/14 placebo)Cycle 5 (N = 7 sorafenib/5 placebo)Cycle 6 (N = 4 sorafenib/3 placebo)Cycle 7 (N = 2 sorafenib/1 placebo)
Placebo + Paclitaxel + Carboplatin1.10.22.23.64.30
Sorafenib + Paclitaxel + Carboplatin2.80.4-0.12.4-0.83.0

[back to top]

Progression Free Survival

"Progression free survival (PFS) is the time (days) from date of randomization to date of first observed disease progression (radiological or clinical, whichever was earlier) or death due to any cause, if death occurred before progression was documented. Since the study was terminated early and 89% of subjects' data were censored, only the number of PFS events (Failed [progressed or died before progression]) is reported, not the usual measure number of days." (NCT00558636)
Timeframe: Up to 5 months after randomization of the first patient

,
InterventionParticipants (Number)
Failed (progressed or died before progression)Censored
Placebo + Paclitaxel + Carboplatin539
Sorafenib + Paclitaxel + Carboplatin542

[back to top]

Duration of Response

Duration of response (PR or better) was defined as the time from the first documented objective PR or CR, whichever was noted earlier, to disease progression or death (if death occurred before progression was documented). Since only 4 subjects had a response, the duration of response was not calculated. (NCT00558636)
Timeframe: Time from first documented objective response (complete response or partial response) to disease progression or death, or to last tumor assessment if censored, up to 5 months after randomization of the first patient.

Interventiondays (Number)
The first subject who showed a responseThe second subject who showed a responseThe third subject who showed a responseThe fourth subject who showed a response
Sorafenib + Paclitaxel + Carboplatin91454653

[back to top] [back to top]

Time To First Disease Progression

Primary Endpoints is efficacy of concurrent erlotinib and chemoradiation as measured by time to progression. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions. All patients will be evaluated by followed up one month after treatment, once a month until recovery from treatment related toxicities, then every 3 months for 2 years, then every 4 months for 2 years (total of 4 years), then annually up to 5 years. (NCT00563784)
Timeframe: From date of registration until the date of first documented progression or death from any cause, or lost to follow up, whichever came first, assessed up to 5 years.

InterventionMonth (Median)
Phase II TARCEVA (Erlotinib) With Chemoradiation in Stage IIIA14

[back to top]

Overall Survival and Disease Local Control Rate

"The Secondary Endpoints is Overall Survival (OS)and Disease Local Control (DLC)Rate. All patients will be followed up to evaluate Overall Survival and Disease Local Control by one month after treatment, once a month until recovery from treatment related toxicities, then every 3 months for 2 years, then every 4 months for 2 years (total of 4 years), then annually up to 5 years.~CT scan of the chest/upper abdomen, MRI of brain or CT, and/or PET scan images are recommended to confirm the recurrence.~Survival endpoints were estimated using the Kaplan-Meier method." (NCT00563784)
Timeframe: OS: From date of registration until the date of first documented death or lost to follow up, whichever came first, accessed up to 5 years. DLC: From date of registration until the date of first documented local disease recurrence, accessed up to 5 years.

Interventionpercentage of participants (Number)
Overall Survival:5-yearDisease Free Survival:5-yearLocal Regional Survival:5-yearDistant Metastasis Free Survival:5-year
Phase II TARCEVA (Erlotinib) With Chemoradiation in Stage IIIA35.925.855.836.5

[back to top]

Overall Response Rate (Patients That Achieve a CR or PR)

Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00564733)
Timeframe: At the end of 4 cycles of treatment, up to 24 weeks.

Interventionparticipants (Number)
Chemotherapy13

[back to top]

Patient Reported Physical Function (Chemotherapy Analysis)

Patient reported physical functioning was measured with physical functioning subscale of the RAND SF-36. The Physical Functioning Subscale consists of 10 items concerning activities of daily living: walking, climbing stairs, bathing, dressing, and performance of physical activities. Each item is rated on a three-point scale of limitation of activity due to the patients' health from 1=limited a lot to 3=not limited. The total PF score is the summation of item scores and then rescaled to 0-100. A larger score suggests better physical functioning. (NCT00565851)
Timeframe: 1. Prior to cycle 1 (baseline), 2. Prior to cycle 3 (6 weeks post cycle 1), 3. Prior to cycle 6 (15 weeks post cycle 1), 4. 6 months post cycle 1, 5. 12 months post cycle 1.

,
Interventionscore on a scale (Least Squares Mean)
Prior to cycle 1 (baseline)Prior to cycle 3Prior to cycle 66 months post cycle 112 months post cycle 1
Paclitaxel and Carboplatin Chemotherapy71.573.271.571.671.8
Paclitaxel and Carboplatin Chemotherapy With Bevacizumab69.469.864.670.270.7

[back to top]

To Determine if the Addition of Bevacizumab Increases the Duration of Overall Survival Relative to Second-line Paclitaxel and Carboplatin Alone in Patients With Recurrent Platinum Sensitive Epithelial Ovarian, Peritoneal Primary or Fallopian Tube Cancer

The treatment regimens will be compared with a logrank procedure which includes all of the patients categorized by their randomly assigned treatment. The logrank test will be stratified by the secondary surgical debulking status (randomized to undergo cytoreduction, vs randomized to not undergo secondary cytoreduction vs not a candidate or did not consent to secondary surgical cytoreduction) and the duration of treatment free-interval prior to enrolling onto this study (6-12 months vs > 12 months). The median duration of follow-up is calculated by the reverse Kaplan-Meier method. (NCT00565851)
Timeframe: The time frame is 82.5 months (median duration of follow-up).

InterventionMonths (Median)
Paclitaxel and Carboplatin Chemotherapy37.3
Paclitaxel and Carboplatin Chemotherapy With Bevacizumab42.2

[back to top]

To Determine if Surgical Secondary Cytoreduction in Addition to Adjuvant Chemotherapy Increases the Duration of Overall Survival in Patients With Recurrent Platinum Sensitive Epithelial Ovarian Cancer, Peritoneal Primary or Fallopian Tube Cancer

The treatment regimens will be compared with a logrank procedure which includes all of the patients categorized by their randomly assigned treatment. The logrank test will be stratified by the secondary surgical debulking status (randomized to undergo cytoreduction, vs randomized to not undergo secondary cytoreduction vs not a candidate or did not consent to secondary surgical cytoreduction) and the duration of treatment free-interval prior to enrolling onto this study (6-12 months vs > 12 months). The median duration of follow-up is calculated by the reverse Kaplan-Meier method. (NCT00565851)
Timeframe: The time frame is 82.5 months (median duration of follow-up)

InterventionMonths (Median)
No Cytoreductive Surgery64.7
Cytoreductive Surgery50.6

[back to top]

Patient Reported Quality of Life (Surgery Analysis)

Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for ovarian cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). Each item in the FACT-O TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). The FACT-O TOI score ranges 0-100 with a large score suggests better QOL. (NCT00565851)
Timeframe: 1. Prior to surgery, 2. 6 weeks post-surgery, 3. 15 weeks post-surgery, 4. 6 months post-surgery, 5. 12 months post-surgery.

,
Interventionscore on a scale (Least Squares Mean)
Prior to surgery6 weeks post-surgery15 weeks post-surgery6 months post-surgery12 months post-surgery
Cytoreductive Surgery74.268.468.873.575.6
No Cytoreductive Surgery74.569.368.772.674.0

[back to top]

Patient Reported Quality of Life (Chemotherapy Analysis)

Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for ovarian cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). Each item in the FACT-O TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). The FACT-O TOI score ranges 0-100 with a large score suggests better QOL. (NCT00565851)
Timeframe: 1. Prior to cycle 1 (baseline), 2. Prior to cycle 3 (6 weeks post cycle 1), 3. Prior to cycle 6 (15 weeks post cycle 1), 4. 6 months post cycle 1, 5. 12 months post cycle 1.

,
Interventionscore on a scale (Least Squares Mean)
Prior to cycle 1 (baseline)Prior to cycle 3Prior to cycle 66 months post cycle 112 months post cycle 1
Paclitaxel and Carboplatin Chemotherapy75.874.273.377.177.0
Paclitaxel and Carboplatin Chemotherapy With Bevacizumab75.373.472.377.277.8

[back to top]

Patient Reported Physical Functioning (Surgery Analysis)

Patient reported physical functioning was measured with physical functioning subscale of the RAND SF-36. The Physical Functioning subscale consists of 10 items concerning activities of daily living: walking, climbing stairs, bathing, dressing, and performance of physical activities. Each item is rated on a three-point scale of limitation of activity due to the patients' health from 1=limited a lot to 3=not limited. The total PF score is the summation of item scores and then rescaled to 0-100. A larger score suggests better physical functioning. This measure was completed by US patients only. (NCT00565851)
Timeframe: 1. Prior to surgery (baseline), 2. 6 weeks post-surgery, 3. 15 weeks post-surgery 4. 6 months post-surgery, 5. 12 months post-surgery

,
Interventionscore on a scale (Least Squares Mean)
Prior to surgery (baseline)6 weeks post-surgery15 weeks post-surgery6 months post-surgery12 months post-surgery
Cytoreductive Surgery71.769.864.670.270.7
No Cytoreductive Surgery73.473.271.571.671.8

[back to top]

Summary of Adverse Events (CTCAE Version 4.0)

Number of treated patients with at least one adverse event reported (assessed by Common Terminology Criteria for Adverse Events (version 4.0)) (NCT00565851)
Timeframe: During treatment period and up to 100 days after stopping the study treatment, a median duration of 82.5 months

InterventionParticipants (Count of Participants)
Arm I (no Surgery; Carboplatin and Paclitaxel)304
Arm II (no Surgery; Carboplatin, Paclitaxel and Bevacizumab)376
Arm III (Surgery; Carboplatin and Paclitaxel)29
Arm IV (Surgery; Carboplatin, Paclitaxel and Bevacizumab)77
Arm V (no Surgery; Carboplatin and Gemcitabine)3
Arm VI (no Surgery; Carboplatin, Gemcitabine and Bevacizumab))9
Arm VII (Surgery; Carboplatin and Gemcitabine)3
Arm VIII (Surgery; Carboplatin, Gemcitabine and Bevacizumab))9

[back to top]

Progression-free Survival (Chemotherapy Analysis)

Progression-free survival was defined as the time from randomization to cancer progression as shown on radiography, according to the RECIST version 1.0 criteria, an increase in the CA125 level according to Gynecologic Cancer InterGroup (GCIG) criteria, global deterioration of health, or death from any cause. (NCT00565851)
Timeframe: Radiographic assessment of disease was conducted during chemotherapy and then every 6 months during the maintenance / surveillance phase

InterventionMonths (Median)
Paclitaxel and Carboplatin Chemotherapy10.4
Paclitaxel and Carboplatin Chemotherapy With Bevacizumab13.8

[back to top]

Progression Free Survival (Surgery Analysis)

Progression-free survival was defined as the time from randomization to cancer progression as shown on radiography, according to the RECIST version 1.0 criteria, an increase in the CA125 level according to Gynecologic Cancer InterGroup (GCIG) criteria, global deterioration of health, or death from any cause. (NCT00565851)
Timeframe: Radiographic assessment of disease (in patients with measurable and non-measurable disease) was conducted Every three months for two years and then every 6 months after completion of chemotherapy during the maintenance/surveillance phase.

InterventionMonths (Median)
No Cytoreductive Surgery16.2
Cytoreductive Surgery18.9

[back to top]

OS in Patients 12-18 Months, Stage 4, MYCN Nonamplified Tumor/Unfavorable Histopathology/Diploid DNA Content/Indeterminant Histology/Ploidy and Patients > 547 Days, Stage 3, MYCN Nonamplified Tumor AND Unfavorable Histopathology/Indeterminant Histology

Kaplan-Meier curves of OS will be plotted, and the proportion of responders to induction therapy will be tabulated. (NCT00567567)
Timeframe: Up to 3 years

Interventionpercent probability (Number)
Single HST (CEM)81.0

[back to top]

Proportion of Patients With a Polymorphism

A chi-square test will be used to test whether the response rate after two cycles of induction therapy and the presence of a polymorphism are independent in the study population. (NCT00567567)
Timeframe: Through completion of a participant's first two cycles during induction, including treatment delays, assessed up to 69 days

InterventionProportion of patients (Number)
Single HST (CEM)0.96
Tandem HST (CEM), Randomly Assigned0.96
Not Assigned0.97

[back to top]

Peak Serum Concentration of Isotretinoin in Patients Enrolled on Either A3973, ANBL0032, ANBL0931, ANBL0532 and Future High Risk Studies

Median peak serum concentration level of isotretinoin for patients enrolled on ANBL0532 (NCT00567567)
Timeframe: Day 1 of each course

InterventionMicromolar (Median)
Single HST (CEM)1.00
Tandem HST (CEM), Randomly Assigned1.36
Not Assigned1.26

[back to top]

Intraspinal Extension

Percentage of patients with primary tumors with intraspinal extension. (NCT00567567)
Timeframe: Up to 5 years

InterventionPercentage of patients (Number)
Single HST (CEM)8.25
Tandem HST (CEM), Randomly Assigned9.66
Not Assigned7.78

[back to top]

Response After Induction Therapy

Per the International Response Criteria: measurable tumor defined as product of longest x widest perpendicular diameter. Elevated catecholamine levels, tumor cell invasion of bone marrow also considered measurable tumor. Complete Response (CR)-no evidence of primary tumor or metastases. Very Good Partial Response (VGPR)->90% reduction of primary tumor; no metastases; no new bone lesions, all pre-existing lesions improved. Partial Response (PR)-50-90% reduction of primary tumor; >50% reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by >50%. Mixed Response (MR)->50% reduction of any measurable lesion (primary or metastases) with <50% reduction in other sites; no new lesions; <25% increase in any existing lesion. No Response (NR)-no new lesions; <50% reduction but <25% increase in any existing legions. Progressive Disease (PD)-any new/increased measurable lesion by >25%; previous negative marrow positive. (NCT00567567)
Timeframe: Study enrollment to the end of induction therapy

InterventionProportion participants that responded (Number)
Single HST (CEM)0.54
Tandem HST (CEM), Randomly Assigned0.48
Not Assigned0.35

[back to top]

Topotecan Systemic Clearance

Median topotecan systemic clearance for courses 1 and 2. (NCT00567567)
Timeframe: Day 1 of courses 1-2

InterventionL/h/m2 (Median)
Single HST (CEM)28.1
Tandem HST (CEM), Randomly Assigned28.1
Not Assigned28.5

[back to top]

Event-free Survival Rate

Comparison of EFS curves, starting from the time of randomization, by treatment group (single CEM vs. tandem CEM) (NCT00567567)
Timeframe: Three years, from time of randomization

Interventionpercent probability (Number)
Single HST (CEM)48.8
Tandem HST (CEM), Randomly Assigned61.8

[back to top]

Enumeration of Peripheral Blood Cluster of Differentiation (CD)3, CD4, and CD8 Cells

A descriptive comparison of the median number of T-cells (CD3, CD4, CD8) between treatment arms (single vs. tandem myeloablative regimens) will be performed. (NCT00567567)
Timeframe: Up to 6 months after completion of assigned myeloablation therapy

,
Interventioncells/mm^3 (Median)
CD3CD4CD8
Single HST (CEM)20073104
Tandem HST (CEM), Randomly Assigned255.581151

[back to top]

Duration of Greater Than or Equal to Grade 3 Neutropenia

A logistic regression model will be used to test the ability of the number of days of neutropenia to predict the presence of a polymorphism. (NCT00567567)
Timeframe: Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 39 days

InterventionDays (Median)
Single HST (CEM)7
Tandem HST (CEM), Randomly Assigned7
Not Assigned7

[back to top]

Duration of Greater Than or Equal to Grade 3 Thrombocytopenia

A logistic regression model will be used to test the ability of the number of days of thrombocytopenia to predict the presence of a polymorphism. (NCT00567567)
Timeframe: Through completion of a participant's first cycle during induction, including treatment delays, assessed up to 46 days

InterventionDays (Median)
Single HST (CEM)4
Tandem HST (CEM), Randomly Assigned4
Not Assigned4

[back to top]

Type of Surgical or Radiotherapy Complication

The Percentage of patients who experienced surgical or radiotherapy complications will be calculated. The complications are: bowel obstruction, chylous leaf, renal injury/atrophy/loss and diarrhea. (NCT00567567)
Timeframe: Up to 3 years

InterventionPercentage of patients (Number)
Single HST (CEM)13.11
Tandem HST (CEM), Randomly Assigned12.50
Not Assigned11.85

[back to top]

EFS Pts Non-randomly Assigned to Single CEM (12-18 Mths, Stg. 4, MYCN Nonamplified Tumor/Unfavorable or Indeterminant Histopathology/Diploid DNA Content & Pts>547 Days, Stg.3, MYCN Nonamplified Tumor AND Unfavorable or Indeterminant Histopathology).

Kaplan-Meier curves of EFS will be plotted, and the proportion of responders to induction therapy will be tabulated. (NCT00567567)
Timeframe: Up to 3 years

Interventionpercent probability (Number)
Single HST (CEM)73.1

[back to top]

Incidence Rate of Local Recurrence

Cumulative incidence rate of local recurrence comparison between ANBL0532 patients randomized or assigned to receive single CEM transplant and boost radiation versus the historical A3973 patients who were transplanted and received boost radiation. (NCT00567567)
Timeframe: Up to 3 years

InterventionPercentage 3-year cumulative incidence (Number)
Single HST (CEM)15.7

[back to top]

Surgical Response

Percentage of patients who achieved a surgical complete resection (NCT00567567)
Timeframe: Up to 3 years

InterventionPercentage of patients (Number)
Single HST (CEM)83.98
Tandem HST (CEM), Randomly Assigned84.09
Not Assigned58.89

[back to top]

Survival Time

Survival time was defined as the time from registration to death due to any cause. (NCT00568451)
Timeframe: up to 2 years

InterventionMonths (Median)
Overall12.5

[back to top]

Time to Disease Progression

Time to disease progression was defined as the time from registration to documentation of disease progression. Disease progression was measured according to the RECIST criteria. Progression: At least a 20 percent increase in the sum of of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT00568451)
Timeframe: up to 2 years

InterventionDays (Median)
Overall74

[back to top]

Number of Participants With an Objective Tumor Status of Either a Complete Response(CR) or Partial Response (PR), According to RECIST (Response Evaluation Criteria in Solid Tumors) Criteria

"Response that was noted on 2 consecutive evaluations for at least 4 weeks apart.~CR: Disappearance of all target lesions; PR: At least a 30 percent of decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Target lesions: All measurable lesions up to a maximum of 10 lesions representative of all involved organs." (NCT00568451)
Timeframe: Every other cycle of therapy (cycle=4 weeks) for the first 6 cycles of treatment

Interventionparticipants (Number)
TMZ (Previously Treated)0
TMZ (Chemo Naive)2

[back to top]

Change in FACT-H&N Score From Baseline to 24 Months

"The FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional.~[Cella, D, et al. JCO 1993(11)]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. [D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL." (NCT00570674)
Timeframe: Baseline and 24 months

Interventionunits on a scale (Median)
All Phase I Participants4.3

[back to top]

Change in FACT-H&N Score From Baseline to 12 Months

"The FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional.~[Cella, D, et al. JCO 1993(11)]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. [D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL." (NCT00570674)
Timeframe: Baseline and 12 months

Interventionunits on a scale (Median)
All Phase I Participants-4.2

[back to top]

Overall Response Rate [Phase I]

Overall response (OR) rate was defined as achieving partial response (PR) or complete response (CR) based on RECIST 1.0 criteria on treatment. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. (NCT00570674)
Timeframe: The primary re-staging assessment for response occurred 8-10 weeks following completion of treatment. Treatment duration was a mean (range) of 7.8 weeks (6.6-10.1).

Interventionproportion of participants (Number)
All Phase I Participants.964

[back to top]

Abraxane Maximum Tolerated Dose (MTD) [Phase I]

The Abraxane MTD in combination with carboplatin and concurrent IMRT is determined by the number of participants who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of participants experience a DLT. If no DLTs are observed then the MTD is not reached but the highest dose may then be the recommended phase II dose. (NCT00570674)
Timeframe: Adverse event assessments occurred weekly on treatment; The observation period for MTD evaluation incorporated the 7 weeks of treatment.

Interventionmg weekly (Number)
All Phase I Participants50

[back to top]

2-Year Overall Survival [Phase I]

2-year overall survival is the proportion of patients alive at 2-years from study entry. (NCT00570674)
Timeframe: All patients were followed for survival for a minimum of 2 years. Median survival follow-up was 44.7 months (range 10-70) in this study cohort.

Interventionproportion of participants (Number)
All Phase I Participants.929

[back to top]

Change in FACT-H&N Score From Baseline to 4 Months

"The FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional.~[Cella, D, et al. JCO 1993(11)]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. [D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL." (NCT00570674)
Timeframe: baseline and 4 months

Interventionunits on a scale (Median)
All Phase I Participants-21

[back to top]

Duration PEG Therapy

Estimated as the time from registration to the date of PEG removal. (NCT00570674)
Timeframe: Assessed until time of PEG removal which was up to 18.4 months in this study cohort.

Interventionmonths (Mean)
All Phase I Participants5.4

[back to top]

Change in FACT-H&N Score From Baseline to 6 Months

"he FACT-H&N is a multidimensional, self-report QoL instrument specifically designed for use with head and neck cancer patients. It is comprised of 27 core items from the FACT-G (Version 4), an established survey which assesses the impact of cancer therapy in four domains: physical, social/family, emotional, and functional.~[Cella, D, et al. JCO 1993(11)]. It is supplemented with a validated measure of 12 site specific items to assess for head and neck related symptoms. [D'Antonio L, Zimmerman G, et al. Cancer 1996 (77)] Each item is rated on a 0 to 4 Likert type scale, and then combined to produce subscale scores for each domain, as well as a global QoL score (range: 0-156). Higher scores represent better QoL. The change score is calculated as post-baseline less baseline; therefore, a negative value indicates a decrease in score and correspondingly a decrease in QoL." (NCT00570674)
Timeframe: Baseline and 6 months

Interventionunits on a scale (Median)
All Phase I Participants-9

[back to top]

Dose Limiting Toxicity (DLT) [Phase I]

Dose limiting toxicities (DLT) were defined as treatment-related: 1) grade 3-4 non-hematological toxicity excluding untreated nausea, vomiting and diarrhea; dysphagia, esophagitis, mucositis/stomatitis, dermatitis/rash, 2) Grade 3 or greater febrile neutropenia occurring during chemoradiotherapy, 3) Grade 4 neutropenia lasting >/= 7 days and 4) Grade 3 thrombocytopenia. Grade 4 toxicities resulting in a treatment breaks > 7 days were considered DLTs. (NCT00570674)
Timeframe: Adverse event assessments occurred weekly on treatment; The observation period for DLT evaluation incorporated the 7 weeks of treatment.

InterventionParticipants with DLT (Number)
Phase I Dose Level 1: ACE-RT0
Phase I Dose Level -1: AC-RT0
Phase I Dose Level 2: AC-RT0
Phase I Dose Level 3: AC-RT0
Phase I Dose Level 4: AC-RT0

[back to top]

Percentage of Participants With Grade 0-1 Observer-rated Dysphagia

To objectively assess dysphagia and aspiration in patients receiving dysphagia/aspiration-sparing IMRT concurrent with chemotherapy, the percentage of participants with observer-rated dysphagia was calculated. (NCT00580983)
Timeframe: 12 months

Interventionpercentage of participants (Number)
Chemo-IMRT94

[back to top]

The Mean Esophageal Radiotherapy Dose in Patients With Strictures and Without Strictures

To assess the relationships between the mean radiotherapy dose delivered and objectively measured dysphagia. (NCT00580983)
Timeframe: 5 years

InterventionGray (Gy) (Mean)
Patients with Strictures (N=5)Patients without strictures (N=68)
Chemo-IMRT4827

[back to top]

Response as Evaluated by Recurrence of Diseases

Evaluate the response to concurrent celecoxib, carboplatin, paclitaxel, and radiotherapy in the treatment of locally advanced SSC of the head and neck. Response is determined by local control only, local and distant metastasis, distant metastasis only, second primary, and surgical salvage. (NCT00581971)
Timeframe: 2 years from end of treatment (Radiation therapy)

InterventionParticipants (Number)
Local Control OnlyLocal Control and Distant MetastasisDistant Metastatsis OnlySecondary Primary - Site UnknownSurgical Salvage
Recurrence62123

[back to top]

Toxicity of Celecoxib With Concurrent Weekly Chemotherapy and Radiotherapy in the Treatment of Locally Advanced or Recurrent Squamous Cell Carcinoma of the Head and Neck.

Particpants experiencing Acute Toxicities > Grade 3 (NCT00581971)
Timeframe: 2 years from radiation therapy

Interventionparticipants (Number)
HematologicDermatitisMucositis/Dysphagia
Acute Toxicity12716

[back to top]

Participant Response

Number of participants evaluated using Response to Treatment in Solid Tumors (RECIST) with definitions of Complete Response (CR): disappearance of all target lesions; and, Partial Response: at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Maintained Continued CR: participants who entered study in a CR and maintained CR post study treatment. Evaluations once a week till Day +30, then Days 30, 60, and 100 then at 6 months or until disease progression. (NCT00583622)
Timeframe: Up to 6 months

Interventionpercentage of participants (Number)
Complete Response (CR)Maintained Continued CRPartial Response (PR)No ResponseNot Evaluable
Bevacizumab + High-Dose Chemotherapy33.342.08.38.38.3

[back to top]

3-year Overall Survival

Number of subjects alive at 3 years (NCT00584857)
Timeframe: 3 years - median followup of 40.4 months

Interventionpartipants (Number)
Paclitaxel/Carboplatin/Megesterol Acetate17

[back to top]

Toxicity

Toxicity secondary to paclitaxel, carboplatin, and megesterol acetate based on NCI common toxicity criteria (NCT00584857)
Timeframe: 3 years

Interventionparticipants (Number)
Paclitaxel/Carboplatin/Megesterol Acetate5

[back to top]

Toxicity

Toxicity secondary to paclitaxel and carboplatin based upon the NCI common toxicity criteria version (NCT00584909)
Timeframe: 4 years

Interventionparticipants (Number)
Paclitaxel + Carboplatin9

[back to top]

Disease-free Survival

Number of months of survival with no evidence of disease (NCT00584909)
Timeframe: 4 years - Median follow up time of 45.3 months

Interventionmonths (Median)
Paclitaxel + Carboplatin50.5

[back to top]

Percentage of Patients With Complete Pathologic Response After 3 Cycles of Treatment

The rate of pathologic complete response (pT0) following three 21 day cycles of neoadjuvant ABI-007, carboplatin and gemcitabine was determined. (NCT00585689)
Timeframe: 63 days (post 3 cycles)

Interventionpercentage of patients (Number)
Neoadjuvant ABI-007, Carboplatin, and Gemcitabine27.3

[back to top]

Improve the Overall Response Rate

assessing the response rate (CR+PR) (NCT00588094)
Timeframe: 2 years

Interventionparticipants (Number)
Complete RemissionComplete Remission/UnconfirmedPartial RemissionProgression of Disease
R-ICEesc4274

[back to top]

Evaluate the Time to Disease Progression

Response and progression will be evaluated in this study using the international criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI, 92(3):205-216, 2000]. Changes in only the largest diameter (uni-dimensional measurement) are used in the RECIST criteria. (NCT00588666)
Timeframe: 3 years

Interventionmonths (Median)
Time to ProgressionOverall Survival
Treatment6.513.9

[back to top]

The Response Rate of Combination Therapy With Bevacizumab, Gemcitabine, and Carboplatin in Patients With Advanced/Metastatic TCC.

(NCT00588666)
Timeframe: 3 years

Interventionpercentage of participants (Number)
Treatment49

[back to top]

Progression-free Survival (PFS)

Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Progression-free survival (PFS) was defined as the time from randomization to date of disease progression or death from any cause, whichever occurred first. Patients who were still alive and progression free were censored at last disease assessment date. Median PFS was estimated using Kaplan-Meier method. (NCT00588770)
Timeframe: on both arms, assessed every 2 cycles during chemotherapy treatment, then assessed every 9 weeks until progression up to 5 years from study entry; patients on arm B were assessed every 2 cycles for additional 12 weeks before changing to every 9 weeks

Interventionmonths (Median)
Chemotherapy Arm (Arm A)4.3
Chemotherapy+Bevacizumab (Arm B)6.0

[back to top]

Overall Survival (OS)

Overall survival (OS) was defined as time from randomization to death from any course. Patients who were alive were censored at the last contact date. Median OS was estimated using the Kaplan-Meier method. (NCT00588770)
Timeframe: assessed every 3 months within 2 years from study entry, then every 6 months up to 5 years from study entry

Interventionmonths (Median)
Chemotherapy Arm (Arm A)11.0
Chemotherapy+Bevacizumab (Arm B)12.6

[back to top]

Overall Response Rate

Overall response rate is defined as number of patients with complete response (CR) or partial response (PR) divided by all patients. Responses are evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) guideline. CR is defined as disappearance of all target and non-target lesions. PR is defined as disappearance of target lesions or at least a 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameters), and persistence of one or more non-target lesion(s). (NCT00588770)
Timeframe: on both arms, assessed every 2 cycles during chemotherapy treatment, then assessed every 9 weeks until progression up to 5 years from study entry; patients on arm B were assessed every 2 cycles for additional 12 weeks before changing to every 9 weeks

Interventionproportion of participants (Number)
Chemotherapy Arm (Arm A)0.245
Chemotherapy+Bevacizumab (Arm B)0.355

[back to top]

Percentage of Participants With Objective Response (OR)

Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response(PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR defined as complete disappearance of all target lesions and non-target disease. No new lesons. PR defined as ≥30% decrease under baseline of the sum of diameters of all target lesions. No unequivocal progression of non-target disease. No new lesions. (NCT00596830)
Timeframe: At baseline, every 6 weeks until radiological disease progression has been documented or the participant begins a subsequent anticancer therapy, up to 22.7 months

Interventionpercentage of participants (Number)
Figitumumab + Paclitaxel and Carboplatin33.0
Paclitaxel and Carboplatin (Chemo)34.5

[back to top]

Progression-Free Survival (PFS)

PFS was defined as the time from randomization to first progression or death due to any cause, whichever came first. Participants last known to be alive and progression-free, with baseline and >=1 on-study assessment, were censored at last disease assessment verifying lack of progression. Progression was determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (20% increase in the sum of target lesions' longest diameter over nadir, unequivocal progression of non-target disease, or appearance of new lesions). (NCT00596830)
Timeframe: At baseline, every 6 weeks until radiological disease progression or the participant begins a subsequent anticancer therapy, up to 22.7 months.

Interventionmonths (Median)
Figitumumab + Paclitaxel and Carboplatin4.7
Paclitaxel and Carboplatin (Chemo)4.6

[back to top]

Number of Participants With Total Anti-drug Antibodies (ADA)

ADAs are immunogenicity indicators to figitumumab. Participants reporting positive for ADAs are indicated by an endpoint titer of no less than 6.64. (NCT00596830)
Timeframe: Cycles 1, 2, and 4 (predose); 28 days and 150 days after the last figi dose

Interventionparticipants (Number)
Figitumumab + Paclitaxel and Carboplatin2
Paclitaxel and Carboplatin (Chemo)0

[back to top]

Overall Survival (OS)

Overall survival was the duration from randomization to death. For participants who are alive, overall survival was censored at the last contact. (NCT00596830)
Timeframe: Baseline until death, assessed monthly after end of treatment, up to 30 months

Interventionmonths (Median)
Figitumumab + Paclitaxel and Carboplatin8.6
Paclitaxel and Carboplatin (Chemo)9.8

[back to top]

Change in FDG-PET Uptake From Baseline to Week 3

Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. (NCT00599755)
Timeframe: Baseline and Week 3

InterventionFold Change in SUVmean (Number)
Gemcitabine and Cisplatin or Gemcitabine and Carboplatin0.75

[back to top]

Change in FDG-PET Uptake From Week 3 to Week 6

Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. (NCT00599755)
Timeframe: Week 3 and Week 6

InterventionFold change in SUVmean (Number)
Gemcitabine and Cisplatin or Gemcitabine and Carboplatin0.85

[back to top]

Repeatability of FDG SUVmean at Baseline

Two positron emission tomography (PET) scans are obtained on different days at baseline, as close together as possible, under conditions of no biological change, to measure FDG SUVmean. The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. (NCT00599755)
Timeframe: Between -14 to -6 days and between -5 to 0 days prior to starting chemotherapy

InterventionSUVmean (Geometric Mean)
Gemcitabine and Cisplatin or Gemcitabine and Carboplatin3.79

[back to top]

Change in FGD-PET Uptake From Baseline to Week 6

"Fold change in SUVmean of FDG uptake with accompanying 80% Confidence Interval.~The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass." (NCT00599755)
Timeframe: Baseline and Week 6

InterventionFold change in SUVmean (Number)
Gemcitabine and Cisplatin or Gemcitabine and Carboplatin0.65

[back to top]

Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy at a Threshold of a 20% Decrease in SUVmean

Metabolic response conversion rate is the number of participants initially classified as non-metabolic responders relative to baseline at week 3 after starting chemotherapy, who are then, relative to week 3, reclassified as metabolic responders at week 6 after starting chemotherapy, based on a pre-specified threshold of a 20% decrease in mean standardized uptake value (SUVmean) of [18F]-Fluorodeoxyglucose (FDG). The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. (NCT00599755)
Timeframe: Weeks 3 and 6 following chemotherapy

InterventionParticipants (Number)
Gemcitabine and Cisplatin or Gemcitabine and Carboplatin10

[back to top]

Metabolic Response Conversion Rate Between 3 and 6 Weeks After Starting Chemotherapy At a Threshold of a 30% Decrease in SUVmean

Metabolic response conversion rate is the number of participants initially classified as non-metabolic responders relative to baseline at week 3 after starting chemotherapy, who are then, relative to week 3, reclassified as metabolic responders at week 6 after starting chemotherapy, based on a pre-specified threshold of a 30% decrease in SUVmean of [18F]-Fluorodeoxyglucose (FDG). The SUVmean was calculated by summing the radioactivity from volumes of interest within each tumor and normalizing for the injected dose and lean body mass. (NCT00599755)
Timeframe: Weeks 3 and 6 following chemotherapy

InterventionParticipants (Number)
Gemcitabine and Cisplatin or Gemcitabine and Carboplatin4

[back to top]

Progression Free Survival (PFS)

"Time in months from start of study treatment to first randomization date of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the first randomization date plus 1) divided by 30.4. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]), or from adverse event (AE) data (where the outcome was Death)." (NCT00600821)
Timeframe: Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years

InterventionMonths (Median)
Axitinib + Paclitaxel + Carboplatin5.7
Bevacizumab + Paclitaxel + Carboplatin6.1

[back to top]

Circulating Endothelial Cells (CEC) in Blood

Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs. (NCT00600821)
Timeframe: Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1

,
InterventionFlourescent Intensity Unit (FIU) (Mean)
Baseline (pVEGFR2+) (n=50, 42)C1 D15 (pVEGFR2+) (n=38, 37)C2 D1 (pVEGFR2+) (n=41, 35)C3 D1 (pVEGFR2+) (n=33, 34)C4 D1 (pVEGFR2+) (n=25, 32)C5 D1 (pVEGFR2+) (n=24, 26)C7 D1 (pVEGFR2+) (n=16, 16)C9 D1 (pVEGFR2+) (n=12, 11)C11 D1 (pVEGFR2+) (n=10, 9)Baseline (VEGFR2+) (n=50, 42)C1 D15 (VEGFR2+) (n=38, 37)C2 D1 (VEGFR2+) (n=41, 35)C3 D1 (VEGFR2+) (n=33, 34)C4 D1 (VEGFR2+) (n=25, 32)C5 D1 (VEGFR2+) (n=24, 25)C7 D1 (VEGFR2+) (n=16, 16)C9 D1 (VEGFR2+) (n=12, 11)C11 D1 (VEGFR2+) (n=10, 9)Baseline (pPDGFRB+) (n=50, 42)C1 D15 (pPDGFRB+) (n=38, 37)C2 D1 (pPDGFRB+) (n=41, 35)C3 D1 (pPDGFRB+) (n=33, 34)C4 D1 (pPDGFRB+) (n=25, 32)C5 D1 (pPDGFRB+) (n=24, 26)C7 D1 (pPDGFRB+) (n=16, 16)C9 D1 (pPDGFRB+) (n=12, 11)C11 D1 (pPDGFRB+) (n=10, 9)Baseline (PDGFRB+) (n=50, 42)C1 D15 (PDGFRB+) (n=38, 37)C2 D1 (PDGFRB+) (n=41, 35)C3 D1 (PDGFRB+) (n=33, 34)C4 D1 (PDGFRB+) (n=25, 32)C5 D1 (PDGFRB+) (n=24, 26)C7 D1 (PDGFRB+) (n=16, 16)C9 D1 (PDGFRB+) (n=12, 11)C11 D1 (PDGFRB+) (n=10, 9)
Axitinib + Paclitaxel + Carboplatin1936317.981822095.741767065.441715569.391472447.682208801.961405048.002280989.751828224.901694522.561634956.891597041.591443986.611181666.881371956.001028231.441485819.581573298.801646702.341253893.971395311.881470448.941046445.722253114.671380133.192172539.751580028.901775826.121589914.371840677.731690163.331288624.641309639.501049351.001666413.671533606.00
Bevacizumab + Paclitaxel + Carboplatin1764577.671810049.322090673.601578940.531815402.161794843.581634128.002283985.002354939.111841618.361740268.051444404.941504595.711259913.441447188.881317560.131476621.001332064.781734853.241599671.651885684.311285439.441514713.972299459.382163313.882225289.183127640.223176459.691819988.051586256.171518360.711408366.911364500.501287039.251625161.641959067.11

[back to top]

Duration of Response (DR)

Time in months from the first documentation of objective tumor response that is subsequently confirmed to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.4. DR was calculated for the subgroup of participants with a confirmed objective tumor response. (NCT00600821)
Timeframe: Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years

InterventionMonths (Median)
Axitinib + Paclitaxel + Carboplatin4.4
Bevacizumab + Paclitaxel + Carboplatin7.0

[back to top]

Overall Survival (OS)

Time in months from date of randomization to date of death due to any cause. OS was calculated as (the death date minus the first randomization date plus 1) divided by 30.4. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). (NCT00600821)
Timeframe: Baseline, every 6 weeks until death or bimonthly after final study visit (up to 2.75 years)

InterventionMonths (Median)
Axitinib + Paclitaxel + Carboplatin10.6
Bevacizumab + Paclitaxel + Carboplatin13.3

[back to top]

Percentage of Participants With Objective Response (OR)

OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed response were those that persisted on repeat imaging study at least 4 weeks after initial documentation of response. CR: disappearance of all lesions (target and/or non target) and no appearance of new lesions. PR: at least 30 percent decrease in sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, without progression of non target lesions and no appearance of new lesions. (NCT00600821)
Timeframe: Baseline, every 6 weeks until disease progression or initiation of subsequent anticancer therapy up to 2.75 years

InterventionPercentage of participants (Number)
Axitinib + Paclitaxel + Carboplatin29.3
Bevacizumab + Paclitaxel + Carboplatin43.3

[back to top]

Plasma Concentration of Soluble Proteins

Plasma concentrations of soluble proteins (soluble- stem-cell factor receptor (sKIT) vascular endothelial growth factor [VEGF], and vascular endothelial growth factor receptor-2 [VEGFR2], VEGFR3) may be associated with tumor angiogenesis or tumor physiology and may correlate with efficacy or biological activity. It is presented as ratio to baseline, which is obtained by dividing the plasma soluble protein concentration at each time point by its concentration at baseline. (NCT00600821)
Timeframe: Baseline, C1D1, C1D15, C2D1, C3D1, C4D1, C5D1, C7D1, C9D1 and C11D1

,
InterventionPicogram/mL (pg/mL) (Mean)
Baseline (SKIT) (n=52, 47)C1 D15 (SKIT) (n=42, 36)C2 D1 (SKIT) (n=41, 43)C3 D1 (SKIT) (n=40, 38)C4 D1 (SKIT) (n=32, 38)C5 D1 (SKIT) (n=27, 34)C7 D1 (SKIT) (n=18, 23)C9 D1 (SKIT) (n=12, 16)C11 D1 (SKIT) (n=11, 13)Baseline (VEGF) (n=50, 48)C1 D15 (VEGF) (n=40, 37)C2 D1 (VEGF) (n=39, 43)C3 D1 (VEGF) (n=39, 38)C4 D1 (VEGF) (n=30, 38)C5 D1 (VEGF) (n=25, 34)C7 D1 (VEGF) (n=18, 23)C9 D1 (VEGF) (n=12, 16)C11 D1 (VEGF) (n=11, 13)Baseline (VEGFR2) (n=52, 48)C1 D15 (VEGFR2) (n=42, 37)C2 D1 (VEGFR2) (n=41, 43)C3 D1 (VEGFR2) (n=40, 38)C4 D1 (VEGFR2) (n=32, 38)C5 D1 (VEGFR2) (n=27, 34)C7 D1 (VEGFR2) (n=18, 23)C9 D1 (VEGFR2) (n=12, 16)C11 D1 (VEGFR2) (n=11, 13)Baseline (VEGFR3) (n=52, 48)C1 D15 (VEGFR3) (n=42, 37)C2 D1 (VEGFR3) (n=41, 43)C3 D1 (VEGFR3) (n=40, 38)C4 D1 (VEGFR3) (n=32, 38)C5 D1 (VEGFR3) (n=27, 34)C7 D1 (VEGFR3) (n=18, 23)C9 D1 (VEGFR3) (n=12, 16)C11 D1 (VEGFR3) (n=11, 13)
Axitinib + Paclitaxel + Carboplatin49740.2953095.4852979.3953817.7556961.4158305.0050701.1148680.4249251.8295.14117.08127.46148.06197.16184.77226.62273.17339.869587.317828.107477.807058.506885.946565.936401.116291.675696.3644390.7733684.2935780.4934147.0019730.9417452.5917896.6721449.1722332.73
Bevacizumab + Paclitaxel + Carboplatin49544.1555801.3955729.6565634.1472671.3268677.2175547.6165990.7866920.38121.83287.19324.33368.23405.13400.16433.30422.38449.929995.0010781.3510330.0010129.479934.2110140.5910339.579421.259222.3124718.3317693.5117798.3715901.3216307.3716381.4715626.3014733.4416048.46

[back to top]

European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Score

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhoea, and financial difficulties). Most questions used 4- point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores averaged, transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms. (NCT00600821)
Timeframe: Day (D) 1 of every cycle (C) then every 3 weeks until final study visit (up to 2.75 years)

,
InterventionUnits on a scale (Mean)
Physical functioning (PF): Baseline (n=58, 59)PF: C2 D1 (n=51, 53)PF: C3 D1 (n=45, 47)PF: C4 D1 (n=37, 48)PF: C5 D1 (n=34, 38)PF: C6 D1 (n=31, 33)PF: C7 D1 (n=27, 30)PF: C8 D1 (n=22, 28)PF: C9 D1 (n=18, 23)PF: C10 D1 (n=17, 20)PF: C11 D1 (n=15, 19)PF: C12 D1 (n=10, 17)PF: C13 D1 (n=8, 14)PF: End of treatment (EOT) (n=27, 38)Role functioning: Baseline (n=58, 58)Role functioning: C2 D1 (n=51, 53)Role functioning: C3 D1 (n=45, 47)Role functioning: C4 D1 (n=37, 48)Role functioning: C5 D1 (n=34, 38)Role functioning: C6 D1 (n=31, 33)Role functioning: C7 D1 (n=28, 30)Role functioning: C8 D1 (n=22, 28)Role functioning: C9 D1 (n=18, 23)Role functioning: C10 D1 (n=17, 20)Role functioning: C11 D1 (n=15, 19)Role functioning: C12 D1 (n=10, 17)Role functioning: C13 D1 (n=8, 14)Role functioning: EOT (n=27, 38)Emotional functioning: Baseline (n=57, 57)Emotional functioning: C2 D1 (n=50, 53)Emotional functioning: C3 D1 (n=45, 48)Emotional functioning: C4 D1 (n=37, 48)Emotional functioning: C5 D1 (n=32, 38)Emotional functioning: C6 D1 (n=29, 32)Emotional functioning: C7 D1 (n=28, 30)Emotional functioning: C8 D1 (n=22, 28)Emotional functioning: C9 D1 (n=18, 23)Emotional functioning: C10 D1 (n=17, 20)Emotional functioning: C11 D1 (n=15, 19)Emotional functioning: C12 D1 (n=10, 17)Emotional functioning: C13 D1 (n=8, 14)Emotional functioning: EOT (n=27, 38)Cognitive Functioning: Baseline (n=57, 57)Cognitive Functioning: C2 D1 (n=50, 53)Cognitive Functioning: C3 D1 (n=45, 48)Cognitive Functioning: C4 D1 (n=37, 48)Cognitive Functioning: C5 D1 (n=32, 38)Cognitive Functioning: C6 D1 (n=29, 32)Cognitive Functioning: C7 D1 (n=28, 30)Cognitive Functioning: C8 D1 (n=22, 28)Cognitive Functioning: C9 D1 (n=18, 23)Cognitive Functioning: C10 D1 (n=17, 20)Cognitive Functioning: C11 D1 (n=15, 19)Cognitive Functioning: C12 D1 (n=10, 17)Cognitive Functioning: C13 D1 (n=8, 14)Cognitive Functioning: EOT (n=27, 38)Social functioning: Baseline (n=57, 57)Social functioning: C2 D1 (n=50, 52)Social functioning: C3 D1 (n=45, 48)Social functioning: C4 D1 (n=37, 48)Social functioning: C5 D1 (n=32, 38)Social functioning: C6 D1 (n=29, 32)Social functioning: C7 D1 (n=28, 30)Social functioning: C8 D1 (n=22, 28)Social functioning: C9 D1 (n=18, 23)Social functioning: C10 D1 (n=17, 20)Social functioning: C11 D1 (n=15, 19)Social functioning: C12 D1 (n=10, 17)Social functioning: C13 D1 (n=8, 14)Social functioning: EOT (n=27, 38)Fatigue: Baseline (n=57, 58)Fatigue: C2 D1 (n=51, 53)Fatigue: C3 D1 (n=45, 47)Fatigue: C4 D1 (n=37, 48)Fatigue: C5 D1 (n=34, 38)Fatigue: C6 D1 (n=31, 33)Fatigue: C7 D1 (n=28, 30)Fatigue: C8 D1 (n=22, 28)Fatigue: C9 D1 (n=18, 23)Fatigue: C10 D1 (n=17, 20)Fatigue: C11 D1 (n=15, 19)Fatigue: C12 D1 (n=10, 17)Fatigue: C13 D1 (n=8, 14)Fatigue: EOT (n=27, 38)Nausea and vomiting: Baseline (n=57, 59)Nausea and vomiting: C2 D1 (n=51, 53)Nausea and vomiting: C3 D1 (n=45, 47)Nausea and vomiting: C4 D1 (n=37, 48)Nausea and vomiting: C5 D1 (n=34, 38)Nausea and vomiting: C6 D1 (n=31, 33)Nausea and vomiting: C7 D1 (n=28, 30)Nausea and vomiting: C8 D1 (n=22, 28)Nausea and vomiting: C9 D1 (n=18, 23)Nausea and vomiting: C10 D1 (n=17, 20)Nausea and vomiting: C11 D1 (n=15, 19)Nausea and vomiting: C12 D1 (n=10, 17)Nausea and vomiting: C13 D1 (n=8, 14)Nausea and vomiting: EOT (n=27, 38)Pain: Baseline (n=57, 59)Pain: C2 D1 (n=51, 53)Pain: C3 D1 (n=45, 48)Pain: C4 D1 (n=37, 48)Pain: C5 D1 (n=34, 38)Pain: C6 D1 (n=31, 33)Pain: C7 D1 (n=28, 30)Pain: C8 D1 (n=22, 28)Pain: C9 D1 (n=18, 23)Pain: C10 D1 (n=17, 20)Pain: C11 D1 (n=15, 19)Pain: C12 D1 (n=10, 17)Pain: C13 D1 (n=8, 14)Pain: EOT (n=27, 38)Dyspnoea: Baseline (n=56, 58)Dyspnoea: C2 D1 (n=51, 52)Dyspnoea: C3 D1 (n=45, 47)Dyspnoea: C4 D1 (n=37, 48)Dyspnoea: C5 D1 (n=34, 38)Dyspnoea: C6 D1 (n=31, 33)Dyspnoea: C7 D1 (n=28, 30)Dyspnoea: C8 D1 (n=22, 28)Dyspnoea: C9 D1 (n=18, 23)Dyspnoea: C10 D1 (n=17, 20)Dyspnoea: C11 D1 (n=15, 19)Dyspnoea: C12 D1 (n=10, 17)Dyspnoea: C13 D1 (n=8, 14)Dyspnoea: EOT (n=27, 38)Insomnia: Baseline (n=57, 58)Insomnia: C2 D1 (n=51, 53)Insomnia: C3 D1 (n=45, 47)Insomnia: C4 D1 (n=37, 48)Insomnia: C5 D1 (n=34, 38)Insomnia: C6 D1 (n=31, 33)Insomnia: C7 D1 (n=28, 30)Insomnia: C8 D1 (n=22, 28)Insomnia: C9 D1 (n=18, 23)Insomnia: C10 D1 (n=17, 20)Insomnia: C11 D1 (n=15, 19)Insomnia: C12 D1 (n=10, 17)Insomnia: C13 D1 (n=8, 14)Insomnia: EOT (n=27, 37)Loss of appetite: Baseline (n=57, 59)Loss of appetite: C2 D1 (n=51, 53)Loss of appetite: C3 D1 (n=44, 47)Loss of appetite: C4 D1 (n=37, 48)Loss of appetite: C5 D1 (n=34, 38)Loss of appetite: C6 D1 (n=31, 33)Loss of appetite: C7 D1 (n=28, 30)Loss of appetite: C8 D1 (n=22, 28)Loss of appetite: C9 D1 (n=18, 23)Loss of appetite: C10 D1 (n=17, 20)Loss of appetite: C11 D1 (n=15, 19)Loss of appetite: C12 D1 (n=10, 17)Loss of appetite: C13 D1 (n=8, 14)Loss of appetite: EOT (n=27, 38)Constipation: Baseline (n=56, 57)Constipation: C2 D1 (n=50, 53)Constipation: C3 D1 (n=45, 47)Constipation: C4 D1 (n=36, 48)Constipation: C5 D1 (n=32, 38)Constipation: C6 D1 (n=28, 33)Constipation: C7 D1 (n=28, 30)Constipation: C8 D1 (n=22, 28)Constipation: C9 D1 (n=18, 23)Constipation: C10 D1 (n=17, 20)Constipation: C11 D1 (n=15, 19)Constipation: C12 D1 (n=10, 17)Constipation: C13 D1 (n=8, 14)Constipation: EOT (n=27, 38)Diarrhoea: Baseline (n=55, 57)Diarrhoea: C2 D1 (n=50, 53)Diarrhoea: C3 D1 (n=45, 48)Diarrhoea: C4 D1 (n=37, 47)Diarrhoea: C5 D1 (n=32, 38)Diarrhoea: C6 D1 (n=29, 32)Diarrhoea: C7 D1 (n=28, 30)Diarrhoea: C8 D1 (n=22, 28)Diarrhoea: C9 D1 (n=18, 23)Diarrhoea: C10 D1 (n=17, 20)Diarrhoea: C11 D1 (n=15, 19)Diarrhoea: C12 D1 (n=10, 17)Diarrhoea: C13 D1 (n=8, 14)Diarrhoea: EOT (n=27, 38)Financial difficulties: Baseline (n=56, 57)Financial difficulties: C2 D1 (n=49, 53)Financial difficulties: C3 D1 (n=45, 48)Financial difficulties: C4 D1 (n=37, 48)Financial difficulties: C5 D1 (n=32, 38)Financial difficulties: C6 D1 (n=29, 32)Financial difficulties: C7 D1 (n=28, 30)Financial difficulties: C8 D1 (n=21, 28)Financial difficulties: C9 D1 (n=18, 23)Financial difficulties: C10 D1 (n=17, 19)Financial difficulties: C11 D1 (n=15, 19)Financial difficulties: C12 D1 (n=10, 17)Financial difficulties: C13 D1 (n=8, 14)Financial difficulties: EOT (n=27, 37)Global health status/QoL: Baseline (n=57, 57)Global health status/QoL: C2 D1 (n=49, 53)Global health status/QoL: C3 D1 (n=45, 48)Global health status/QoL: C4 D1 (n=37, 47)Global health status/QoL: C5 D1 (n=32, 38)Global health status/QoL: C6 D1 (n=29, 32)Global health status/QoL: C7 D1 (n=28, 30)Global health status/QoL: C8 D1 (n=22, 28)Global health status/QoL: C9 D1 (n=18, 22)Global health status/QoL: C10 D1 (n=17, 20)Global health status/QoL: C11 D1 (n=15, 19)Global health status/QoL: C12 D1 (n=10, 17)Global health status/QoL: C13 D1 (n=8, 14)Global health status/QoL: EOT (n=27, 38)
Axitinib + Paclitaxel + Carboplatin66.2967.4565.7867.8861.1865.8666.4267.2766.3068.6360.6771.3366.6762.9660.9264.3858.1567.1257.3562.9055.3665.1563.8966.6760.0075.0062.5057.4169.7478.3375.1975.7577.6078.7478.5777.6574.0777.9470.0074.1777.0868.5280.1284.0085.1984.6884.3786.7879.7689.3984.2688.2382.2290.0085.4277.7871.3569.6771.1173.4265.1070.1164.8871.9774.0772.5566.6771.6756.2569.1440.4543.5747.4142.3444.6145.1647.8244.9540.1241.8347.7837.7850.0051.038.777.1911.1110.8113.2413.4415.4814.409.2611.7714.4515.0012.5016.0531.2929.7430.0026.5825.0031.1828.5728.0333.3330.3943.3335.0035.4238.2732.7432.0338.5233.3336.2736.5638.0927.2725.9327.4537.7823.3337.5035.8046.2036.6030.3724.3228.4324.7323.8121.2125.9327.4533.3326.6712.5028.3929.8223.5333.3326.1330.3927.9639.2936.3631.4839.2233.3316.6729.1739.5115.4821.3318.5218.5218.7522.6225.0019.709.2617.6522.2220.0016.6720.996.6711.3315.5513.5122.9221.8416.6724.2427.7823.5331.1143.3333.3323.4622.6221.7725.9321.6226.0426.4426.1928.5727.7827.4520.0013.3320.8323.4653.2258.1656.6757.2158.0753.4555.6556.8256.4855.3947.7854.1753.1349.38
Bevacizumab + Paclitaxel + Carboplatin75.0075.4778.1673.7875.0973.9474.8977.1474.5781.3378.2578.4379.0564.9160.6365.4170.9267.3666.2367.6863.8971.4370.2970.8371.9370.5980.9557.9063.7473.6478.7676.0478.5177.3579.4581.2578.5078.3382.4677.4583.9370.1883.3384.2885.4282.6483.3381.2585.5688.6986.2390.0085.9687.2595.2478.9565.5075.3274.6571.5375.8871.8872.2272.0281.1679.1778.9580.3980.9565.7938.8936.4833.8037.8536.8433.5040.7432.1428.9830.0028.0729.4126.1943.139.895.355.677.297.4610.619.445.955.078.335.266.685.957.9035.3128.3018.7525.3524.1225.2527.2222.6227.5424.1718.4223.5316.6734.6536.2124.3619.1521.5323.6820.2021.1116.6721.7418.3317.5421.5719.0533.3337.9328.3029.0827.0823.6824.2425.5519.0523.1920.0022.8123.5316.6736.9431.6420.7517.0223.6121.0523.2324.4419.0513.0420.0015.7923.5316.6737.7221.0520.1314.8913.1921.0519.197.782.385.805.008.775.884.7614.035.8510.069.725.677.8910.4211.114.765.8010.000.000.007.143.5121.6420.1218.0520.8321.0520.8326.6721.4317.3924.5619.3017.6516.6728.8354.9759.5959.7257.8061.8460.9458.6160.7164.4062.5063.6063.7358.3350.22

[back to top]

Circulating Endothelial Cells (CEC) in Blood: Total CEC

Circulating endothelial cells (CECs) are noninvasive marker of vascular damage, remodeling, and dysfunction. Total CEC, plasma-vascular endothelial growth factor receptor-2 (pVEGFR2), VEGFR2, p-Beta-type platelet-derived growth factor receptor (pPDGFRB+) and PDGFRB+ were explored using CECs. Blood was collected to analyze effects of therapy on the number, viability/apoptotic state, and/or target activity/expression in CECs. (NCT00600821)
Timeframe: Baseline (C1 D1), C1 D15, C2 D1, C3 D1, C4 D1, C5 D1, C7 D1, C9 D1 and C11 D1

,
InterventionCells/milliliter (cells/mL) (Mean)
Baseline (n=39, 37)C1 D15 (n=27, 29)C2 D1 (n=32, 28)C3 D1 (n=24, 30)C4 D1 (n=20, 27)C5 D1 (n=18, 23)C7 D1 (n=11, 14)C9 D1 (n=7, 7)C11 D1 (n=6, 6)
Axitinib + Paclitaxel + Carboplatin46815.3811780.1529229.0919517.5024556.0528266.2271770.9158680.00116620.83
Bevacizumab + Paclitaxel + Carboplatin16960.4121882.4140507.3625215.7041944.5937468.1336964.36107978.14120847.67

[back to top]

European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Lung Cancer-13 (QLQ- LC13) Score

QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The 13 questions comprised 1 multi-item scale for dyspnoea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, chest pain, arm pain, other pain, and medicine for pain). Recall period: past week; response range: not at all to very much. Scale score range: 0 to 100. Higher symptom score = greater degree of symptoms. (NCT00600821)
Timeframe: Day 1 of every cycle then every 3 weeks until final study visit (up to 2.75 years)

,
InterventionUnits on a scale (Mean)
Cough: Baseline (n=56, 59)Cough: C2 D1 (n=50, 53)Cough: C3 D1 (n=46, 47)Cough: C4 D1 (n=37, 48)Cough: C5 D1 (n=33, 38)Cough: C6 D1 (n=29, 33)Cough: C7 D1 (n=28, 29)Cough: C8 D1 (n=22, 27)Cough: C9 D1 (n=18, 23)Cough: C10 D1 (n=17, 20)Cough: C11 D1 (n=15, 19)Cough: C12 D1 (n=10, 17)Cough: C13 D1 (n=8, 14)Cough: End of treatment (EOT) (n=26, 38)Haemoptysis: Baseline (n=56, 59)Haemoptysis: C2 D1 (n=50, 53)Haemoptysis: C3 D1 (n=44, 47)Haemoptysis: C4 D1 (n=36, 48)Haemoptysis: C5 D1 (n=33, 38)Haemoptysis: C6 D1 (n=29, 33)Haemoptysis: C7 D1 (n=27, 29)Haemoptysis: C8 D1 (n=22, 27)Haemoptysis: C9 D1 (n=18, 23)Haemoptysis: C10 D1 (n=17, 20)Haemoptysis: C11 D1 (n=15, 19)Haemoptysis: C12 D1 (n=10, 17)Haemoptysis: C13 D1 (n=8, 14)Haemoptysis: EOT (n=26, 38)Dyspnoea: Baseline (n=56, 58)Dyspnoea: C2 D1 (n=48, 53)Dyspnoea: C3 D1 (n=45, 43)Dyspnoea: C4 D1 (n=36, 45)Dyspnoea: C5 D1 (n=33, 37)Dyspnoea: C6 D1 (n=28, 31)Dyspnoea: C7 D1 (n=27, 27)Dyspnoea: C8 D1 (n=22, 26)Dyspnoea: C9 D1 (n=18, 22)Dyspnoea: C10 D1 (n=17, 19)Dyspnoea: C11 D1 (n=15, 18)Dyspnoea: C12 D1 (n=10, 17)Dyspnoea: C13 D1 (n=8, 14)Dyspnoea: EOT (n=25, 37)Sore Mouth: Baseline (n=56, 58)Sore Mouth: C2 D1 (n=51, 53)Sore Mouth: C3 D1 (n=45, 47)Sore Mouth: C4 D1 (n=37, 48)Sore Mouth: C5 D1 (n=33, 38)Sore Mouth: C6 D1 (n=28, 33)Sore Mouth: C7 D1 (n=28, 29)Sore Mouth: C8 D1 (n=22, 27)Sore Mouth: C9 D1 (n=18, 23)Sore Mouth: C10 D1 (n=17, 20)Sore Mouth: C11 D1 (n=15, 19)Sore Mouth: C12 D1 (n=10, 17)Sore Mouth: C13 D1 (n=8, 14)Sore Mouth: EOT (n=26, 38)Dysphagia: Baseline (n=56, 59)Dysphagia: C2 D1 (n=51, 53)Dysphagia: C3 D1 (n=46, 47)Dysphagia: C4 D1 (n=37, 48)Dysphagia: C5 D1 (n=32, 38)Dysphagia: C6 D1 (n=28, 33)Dysphagia: C7 D1 (n=28, 28)Dysphagia: C8 D1 (n=22, 27)Dysphagia: C9 D1 (n=18, 23)Dysphagia: C10 D1 (n=17, 20)Dysphagia: C11 D1 (n=15, 19)Dysphagia: C12 D1 (n=10, 17)Dysphagia: C13 D1 (n=8, 14)Dysphagia: EOT (n=26, 38)Peripheral neuropathy: Baseline (n=56, 59)Peripheral neuropathy: C2 D1 (n=51, 53)Peripheral neuropathy: C3 D1 (n=46, 47)Peripheral neuropathy: C4 D1 (n=37, 48)Peripheral neuropathy: C5 D1 (n=33, 38)Peripheral neuropathy: C6 D1 (n=29, 33)Peripheral neuropathy: C7 D1 (n=28, 29)Peripheral neuropathy: C8 D1 (n=22, 27)Peripheral neuropathy: C9 D1 (n=17, 23)Peripheral neuropathy: C10 D1 (n=17, 20)Peripheral neuropathy: C11 D1 (n=14, 19)Peripheral neuropathy: C12 D1 (n=9, 17)Peripheral neuropathy: C13 D1 (n=8, 14)Peripheral neuropathy: EOT (n=25, 38)Alopecia: Baseline (n=56, 59)Alopecia: C2 D1 (n=50, 53)Alopecia: C3 D1 (n=46, 45)Alopecia: C4 D1 (n=37, 45)Alopecia: C5 D1 (n=33, 35)Alopecia: C6 D1 (n=28, 32)Alopecia: C7 D1 (n=28, 28)Alopecia: C8 D1 (n=21, 27)Alopecia: C9 D1 (n=18, 23)Alopecia: C10 D1 (n=17, 20)Alopecia: C11 D1 (n=14, 18)Alopecia: C12 D1 (n=10, 17)Alopecia: C13 D1 (n=8, 14)Alopecia: EOT (n=26, 37)Chest pain: Baseline (n=56, 59)Chest pain: C2 D1 (n=51, 53)Chest pain: C3 D1 (n=45, 47)Chest pain: C4 D1 (n=36, 48)Chest pain: C5 D1 (n=33, 38)Chest pain: C6 D1 (n=28, 33)Chest pain: C7 D1 (n=28, 28)Chest pain: C8 D1 (n=22, 27)Chest pain: C9 D1 (n=18, 23)Chest pain: C10 D1 (n=17, 20)Chest pain: C11 D1 (n=15, 19)Chest pain: C12 D1 (n=10, 16)Chest pain: C13 D1 (n=7, 14)Chest pain: EOT (n=26, 37)Arm/shoulder pain: Baseline (n=56, 59)Arm/shoulder pain: C2 D1 (n=51, 53)Arm/shoulder pain: C3 D1 (n=45, 47)Arm/shoulder pain: C4 D1 (n=37, 47)Arm/shoulder pain: C5 D1 (n=33, 38)Arm/shoulder pain: C6 D1 (n=29, 33)Arm/shoulder pain: C7 D1 (n=28, 29)Arm/shoulder pain: C8 D1 (n=22, 26)Arm/shoulder pain: C9 D1 (n=18, 23)Arm/shoulder pain: C10 D1 (n=17, 20)Arm/shoulder pain: C11 D1 (n=14, 19)Arm/shoulder pain: C12 D1 (n=10, 17)Arm/shoulder pain: C13 D1 (n=8, 14)Arm/shoulder pain: EOT (n=26, 38)Other pain: Baseline (n=52, 57)Other pain: C2 D1 (n=49, 50)Other pain: C3 D1 (n=46, 47)Other pain: C4 D1 (n=36, 45)Other pain: C5 D1 (n=32, 38)Other pain: C6 D1 (n=28, 33)Other pain: C7 D1 (n=28, 28)Other pain: C8 D1 (n=22, 26)Other pain: C9 D1 (n=15, 23)Other pain: C10 D1 (n=16, 19)Other pain: C11 D1 (n=14, 18)Other pain: C12 D1 (n=10, 17)Other pain: C13 D1 (n=8, 14)Other pain: EOT (n=25, 37)Medicine for pain: Baseline (n=37, 35)Medicine for pain: C3 D1 (n=29, 24)Medicine for pain: C4 D1 (n=19, 29)Medicine for pain: C5 D1 (n=17, 22)Medicine for pain: C6 D1 (n=16, 17)Medicine for pain: C7 D1 (n=15, 14)Medicine for pain: C8 D1 (n=13, 16)Medicine for pain: C9 D1 (n=6, 14)Medicine for pain: C10 D1 (n=10, 10)Medicine for pain: C11 D1 (n=9, 9)Medicine for pain: C12 D1 (n=6, 9)Medicine for pain: C13 D1 (n=0, 0)Medicine for pain: EOT (n=15, 19)Medicine for pain: C2 D1 (n=30, 35)
Axitinib + Paclitaxel + Carboplatin37.5030.6728.9829.7322.2226.4425.0021.2120.3723.5324.4426.6633.3333.332.982.670.760.931.013.450.000.000.000.000.000.004.170.0029.1729.8633.8332.1030.3035.3230.4524.7527.7828.7627.4123.3337.5034.223.5718.9518.5221.6223.2316.6717.8616.679.2619.6122.2216.6725.008.976.5511.7613.779.9112.5013.1011.9016.679.2621.5724.446.6720.837.699.5224.8437.6845.0550.5155.1748.8157.5845.1045.1050.0055.5658.3337.332.9869.3373.9165.7761.6269.0539.2942.8627.7831.3716.6713.338.3333.3323.8118.9514.8114.8111.1115.4811.9013.6412.9613.7224.4413.3319.0530.7720.8320.9114.8118.9214.1416.0915.4816.6714.8113.7326.1923.3320.8321.8028.8526.5334.0625.9325.0029.7632.1416.6731.1125.0042.8633.3329.1734.6760.3665.5263.1670.5966.6775.5666.6772.2373.3448.1555.56NA60.0062.22
Bevacizumab + Paclitaxel + Carboplatin38.4230.1928.3727.0828.0726.2625.2919.7524.6421.6726.3129.4121.4333.333.391.895.673.473.513.033.451.230.000.000.000.000.005.2631.4223.9020.4124.6923.1221.8620.1621.3718.6919.8819.7522.2216.6733.631.159.439.228.3311.406.066.903.705.8010.008.777.844.764.396.786.924.962.784.397.075.951.231.456.671.753.924.767.8915.2533.9634.7538.1942.1152.5354.0250.6256.5248.3349.1254.9047.6240.352.2671.7068.8960.0064.7661.4640.4844.4431.8811.6716.679.807.1427.0320.9010.065.679.033.511.013.573.707.258.337.022.084.7615.3120.3420.755.6717.0214.915.0514.9414.1013.0420.0015.7925.4919.0523.6825.1532.6723.4028.1526.3227.2735.7125.6431.8822.8125.9327.4526.1929.7366.6768.0672.4172.7372.5566.6775.0069.0560.0081.4870.37NA66.6771.43

[back to top]

Safety and Toxicity According to CTCAE v3.0

Common dose limiting toxicities. (NCT00601718)
Timeframe: 3-5 weeks post end of treatment

InterventionParticipants (Count of Participants)
InfectionHypokalemiaTransaminitisGrade 3 related gastrointestinal toxicity
Treatment (Enzyme Inhibitor, Monoclonal Antibody, Chemotherapy2229

[back to top]

Ability to Proceed to Peripheral Blood Stem Cell Collection Following Treatment

(NCT00601718)
Timeframe: 1-3 weeks post end of treatment

InterventionParticipants (Count of Participants)
Treatment (Enzyme Inhibitor, Monoclonal Antibody, Chemotherapy20

[back to top]

Efficacy (Response Rate) of Vorinostat Combined With RICE Chemotherapy

(NCT00601718)
Timeframe: 3-5 weeks post end of treatment

InterventionParticipants (Count of Participants)
Treatment (Enzyme Inhibitor, Monoclonal Antibody, Chemotherapy19

[back to top]

Maximum Tolerated Dose of Vorinostat

(NCT00601718)
Timeframe: 28 days post last dose of study drug

Interventionmg twice daily X 5 days (Number)
Treatment (Enzyme Inhibitor, Monoclonal Antibody, Chemotherapy500

[back to top]

Feasibility and Toxicity of Administering Oral Maintenance Therapy in Children <3 Years of Age as Measured by the Percentage of Total Scheduled Maintenance Doses Received

These data are based on patient diaries. For children <3 years of age, we will calculate the percentage of total scheduled doses each patient received per course for each of the oral maintenance courses and report the overall average number percentage of doses received per course across patients. If patients received all planned doses, their percentage would be 100%. If the average percentage was less than 75%, then feasibility would be in question. (NCT00602667)
Timeframe: From start of oral maintenance therapy (approximately 6 months after on-study date) to completion of oral maintenance therapy (up to 1 year after on-study date)

InterventionPercentage of scheduled doses received (Mean)
Low-Risk Group96
Intermediate-Risk Group91
High-Risk Group98

[back to top]

Feasibility and Toxicity of Administering Consolidation Therapy Including Cyclophosphamide and Pharmacokinetically Targeted Topotecan to Patients With Metastatic Disease Based on the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity

For the subset of patients with metastatic disease (high-risk group patients), during consolidation, we will calculate the number and proportion of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity. Patients were to received 2 courses of consolidation chemotherapy and then maintenance therapy. (NCT00602667)
Timeframe: At completion of consolidation therapy (up to 6 months after on-study date)

InterventionPercentage of courses delayed (Number)
High-Risk Group2.6

[back to top]

Event-free Survival (EFS) Compared to Historical Controls

EFS was measured from the date of initial treatment to the earliest date of disease progression, second malignancy or death for patients who fail; and to the date of last contact for patients who remain at risk for failure. 1-year EFS estimates are reported by risk group. EFS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals. (NCT00602667)
Timeframe: From date on treatment until date of first event (progression, second malignancy or death) or until date of last contact, assessed up to 10 years

InterventionPercent probability (Number)
SJYC07 Low-risk Medulloblastoma Patients73.9
SJYC07 Intermediate-risk Medulloblastoma Patients46.9
SJYC07 High-risk Medulloblastoma Patients30.8

[back to top]

Erlotinib AUC0-24h

Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose

Interventionµmol·h/L (Median)
Low-Risk Group31.0
Intermediate-Risk Group23.5
High-Risk Group22.0

[back to top]

Erlotinib Apparent Volume of Central Compartment

Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent volume of central compartment are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose

InterventionL/m^2 (Median)
Low-Risk Group72.9
Intermediate-Risk Group61.7
High-Risk Group104.8

[back to top]

Erlotinib Apparent Oral Clearance

Erlotinib plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of erlotinib apparent oral clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose

InterventionL/h/m^2 (Median)
Low-Risk Group6.53
Intermediate-Risk Group7.79
High-Risk Group8.40

[back to top]

Cyclophosphamide Clearance in Induction Chemotherapy

Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

InterventionL/h/m^2 (Median)
Low-Risk Group2.40
Intermediate-Risk Group2.23
High-Risk Group2.25

[back to top]

Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 2

Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

InterventionL/h/m^2 (Median)
Low-Risk Group2.48
Intermediate-Risk Group2.55
High-Risk Group2.37

[back to top]

Cyclophosphamide Clearance in Consolidation Chemotherapy Cycle 1

Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

InterventionL/h/m^2 (Median)
Low-Risk Group2.39
Intermediate-Risk Group2.08
High-Risk Group2.43

[back to top]

Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1

Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide AUC0-24h are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose

Interventionµmol·h/L (Median)
Low-Risk Group39.9
Intermediate-Risk Group38.7
High-Risk Group42.2

[back to top]

Cyclophosphamide AUC0-24h in Induction Chemotherapy

Cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group2070
Intermediate-Risk Group2150
High-Risk Group2105

[back to top]

Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2

Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group1966
Intermediate-Risk Group799
High-Risk Group899

[back to top]

Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1

Cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group1968
Intermediate-Risk Group1504
High-Risk Group868

[back to top]

Cyclophosphamide Apparent Oral Clearance in Maintenance Chemotherapy Cycle A1

Cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of cyclophosphamide apparent oral clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 0.5, 1.75, 3 and 6 hours post-dose

InterventionL/h/m^2 (Median)
Low-Risk Group2.95
Intermediate-Risk Group2.83
High-Risk Group2.74

[back to top]

CEPM AUC0-24h in Maintenance Chemotherapy Cycle A1

Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose

Interventionµmol·h/L (Median)
Low-Risk Group1.59
Intermediate-Risk Group1.65
High-Risk Group1.41

[back to top]

CEPM AUC0-24h in Induction Chemotherapy

Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected on day 9 in one induction cycle. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group140.2
Intermediate-Risk Group137.8
High-Risk Group135.3

[back to top]

CEPM AUC0-24h in Consolidation Chemotherapy Cycle 2

Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group132.7
Intermediate-Risk Group46.8
High-Risk Group44.0

[back to top]

CEPM AUC0-24h in Consolidation Chemotherapy Cycle 1

Carboxyethylphosphoramide mustard (CEPM) plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of CEPM AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group128.9
Intermediate-Risk Group62.2
High-Risk Group51.8

[back to top]

4-OH Cyclophosphamide AUC0-24h in Maintenance Chemotherapy Cycle A1

4-OH cyclophosphamide plasma concentration-time data are collected on day 1 of maintenance cycle A1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 0.5, 1.75, 3, 6, and 24 hours post-dose

Interventionµmol·h/L (Median)
Low-Risk Group1.98
Intermediate-Risk Group1.96
High-Risk Group1.82

[back to top]

4-OH Cyclophosphamide AUC0-24h in Induction Chemotherapy

4-OH cyclophosphamide plasma concentration-time data are collected on day 9 in one cycle of induction chemotherapy. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group116.4
Intermediate-Risk Group111.3
High-Risk Group109.1

[back to top]

4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 2

4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 2. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group95.9
Intermediate-Risk Group49.5
High-Risk Group43.5

[back to top]

4-OH Cyclophosphamide AUC0-24h in Consolidation Chemotherapy Cycle 1

4-OH cyclophosphamide plasma concentration-time data are collected in consolidation cycle 1. Individual estimates of 4-OH cyclophosphamide AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, end of infusion, 3, 6, and 24 hours from end of cyclophosphamide infusion

Interventionµmol·h/L (Median)
Low-Risk Group96.8
Intermediate-Risk Group48.7
High-Risk Group39.8

[back to top]

Pharmacogenetic Variation on Central Nervous System Transmitters

Frequencies of genetic polymorphisms were reported. (NCT00602667)
Timeframe: At study enrollment (Day 0)

InterventionParticipants (Count of Participants)
Genetic Polymorphisms for monoamine oxidase A (MAOA) rs632372067969Genetic Polymorphisms for catecholamine-O-methyltransferase (COMT) rs468072067969Genetic Polymorphisms for dopamine receptor D (DRD3) rs628072067969
AGCCTCTTGGAATG
Patients With Neurotransmitter Studies2
Patients With Neurotransmitter Studies13
Patients With Neurotransmitter Studies7
Patients With Neurotransmitter Studies5
Patients With Neurotransmitter Studies0
Patients With Neurotransmitter Studies6
Patients With Neurotransmitter Studies4

[back to top]

Numbers of Patients With Molecular Abnormalities by Tumor Type

Alterations included single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations. Cytogenetic information shows gains and losses as specified in the table of measured values. (NCT00602667)
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

,,,,,,
InterventionParticipants (Count of Participants)
PTCH1 alterationSUFU alterationKMT2D alterationSMO alterationBCOR alterationPTEN alterationBRCA2 alterationGLI2 alterationSMARCA4 alterationTP53 alterationMYCN amplificationchr2p gain/amplificationchr2p loss/deletionchr2q gain/amplificationchr2q loss/deletionchr6p gain/amplificationchr6p loss/deletionchr6q gain/amplificationchr6q loss/deletionchr8p gain/amplificationchr8p loss/deletionchr8q gain/amplificationchr8q loss/deletionchr9p gain/amplificationchr9p loss/deletionchr9q gain/amplificationchr9q loss/deletionchr10p gain/amplificationchr10p loss/deletionchr10q gain/amplificationchr10q loss/deletionchr20p gain/amplificationchr20p loss/deletionchr20q gain/amplificationchr20q loss/deletion
High-risk Group 3 Patients00000000001101032320706030307080404
High-risk Group 4 Patients00000000000000000000101000000000000
High-risk SHH Patients31310000000404000000000301200010101
Intermediate-risk Group 3 Patients00000000100010120201221100005050303
Intermediate-risk Group 4 Patients00000000000010110100404101000000000
Intermediate-risk SHH Patients41100000001000000000000400500020100
Low-risk SHH Patients76521100200505010101010442600030201

[back to top]

Numbers of Patients With Gene Alterations

Gene alterations, which include single nucleotide variants (SNPs), amplifications, deletions, translocations, indels, and germline alterations are shown for specific genes of interest in the results table. (NCT00602667)
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

,,
InterventionParticipants (Count of Participants)
PTCH1 alterationSUFU alterationKMT2D alterationSMO alterationBCOR alterationPTEN alterationBRCA2 alterationGLI2 alterationSMARCA4 alterationTP53 alterationMYCN alteration
High-Risk Group31310000001
Intermediate-Risk Group41100000101
Low-Risk Group76521100200

[back to top]

Number of Successful Collections for Frozen and Fixed Tumor Samples

Successful collections will be defined as the number of patients who have frozen/fixed tumor samples available. (NCT00602667)
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

,,
InterventionParticipants (Count of Participants)
Number with frozen tumor tissueNumber with fixed tumor tissue
High-Risk Group3271
Intermediate-Risk Group73153
Low-Risk Group2754

[back to top]

Number of Participants With Chromosomal Abnormalities

Amplifications and deletions (gains and losses) for chromosomes of interest are shown in the table of measured values. (NCT00602667)
Timeframe: Based on samples obtained at the time of initial surgery or repeat surgery prior to treatment

,,
InterventionParticipants (Count of Participants)
chr2p gain/amplificationchr2p loss/deletionchr2q gain/amplificationchr2q loss/deletionchr6p gain/amplificationchr6p loss/deletionchr6q gain/amplificationchr6q loss/deletionchr8p gain/amplificationchr8p loss/deletionchr8q gain/amplificationchr8q loss/deletionchr9p gain/amplificationchr9p loss/deletionchr9q gain/amplificationchr9q loss/deletionchr10p gain/amplificationchr10p loss/deletionchr10q gain/amplificationchr10q loss/deletionchr20p gain/amplificationchr20p loss/deletionchr20q gain/amplificationchr20q loss/deletion
High-Risk Group606032320807331507090505
Intermediate-Risk Group121230302635601505070403
Low-Risk Group505010101010442600030201

[back to top]

Number and Type of Genetic Polymorphisms

Types of genetic polymorphisms of neurotransmitters were examined. We studied 3 genetic polymorphisms; these were types of genetic polymorphisms involved in dopamine metabolism. They were as follows: rs6323, rs4680, and rs6280. (NCT00602667)
Timeframe: At study enrollment (Day 0)

InterventionParticipants (Count of Participants)
rs6323rs4680rs6280
Number of Patients With Neurotransmitter Studies171717

[back to top]

Concentration of Cerebrospinal Fluid Neurotransmitters

Concentrations of various neurotransmitters in cerebrospinal fluid were measured at 5 timepoints. The median concentration of each neurotransmitter at each time point was calculated and provided with a full range. (NCT00602667)
Timeframe: Baseline, at the completion of therapy, and every 12 months up to 36 months after off therapy date

Interventionng/ml (Median)
Dopamine concentration at baselineDopamine concentration at completion of treatmentDopamine concentration at 12 months off treatmentDopamine concentration at 24 months off treatmentDopamine concentration at 36 months off treatment3,4-dihydroxyphenylacetic acid concentration at baseline3,4-dihydroxyphenylacetic acid concentration at completion of treatment3,4-dihydroxyphenylacetic acid concentration at 12 months off treatment3,4-dihydroxyphenylacetic acid concentration at 24 months off treatment3,4-dihydroxyphenylacetic acid concentration at 36 months off treatmentHydroxytryptamine concentration at baselineHydroxytryptamine concentration at completion of treatmentHydroxytryptamine concentration at 12 months off treatmentHydroxytryptamine concentration at 24 months off treatmentHydroxytryptamine concentration at 36 months off treatmentHydroxyindoleacetic acid concentration at baselineHydroxyindoleacetic acid concentration at completion of treatmentHydroxyindoleacetic acid concentration at 12 months off treatmentHydroxyindoleacetic acid concentration at 24 months off treatmentHydroxyindoleacetic acid concentration at 36 months off treatmentHomovanillic acid concentration at baselineHomovanillic acid concentration at completion of treatmentHomovanillic acid concentration at 12 months off treatmentHomovanillic acid concentration at 24 months off treatmentHomovanillic acid concentration at 36 months off treatment
Patients With Neurotransmitter Studies3.163.706.434.464.052.561.621.041.521.002.382.012.002.441.6252.0352.7235.7233.9831.5682.44114.1368.2888.2779.78

[back to top]

Topotecan Clearance in Consolidation Chemotherapy

Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, 5 min., 1, and 3 hours from end of infusion

InterventionL/h/m^2 (Median)
Intermediate-Risk Group30.3
High-Risk Group26.40

[back to top]

Topotecan AUC0-24h in Maintenance Chemotherapy

Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 0.25, 1.5, 6, and 24 hours post-dose

Interventionµg·h/L (Median)
Low-Risk Group10.90
Intermediate-Risk Group11.60
High-Risk Group10.33

[back to top]

Topotecan AUC0-24h in Consolidation Chemotherapy

Topotecan plasma concentration-time data are collected on day 1 of consolidation cycle 1 after a single IV dose. Individual estimates of topotecan AUC0-24h (area under concentration curve from time 0 to 24 hours post- dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion, 5 min., 1, 3, and 24 hours from end of infusion

Interventionµg·h/L (Median)
Intermediate-Risk Group117
High-Risk Group116

[back to top]

Topotecan Apparent Oral Clearance in Maintenance Chemotherapy

Topotecan plasma concentration-time data are collected on day 1 of maintenance cycle A1 after a single oral dose. Individual estimates of topotecan apparent oral clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 0.25, 1.5 and 6 hours post-dose

InterventionL/h (Median)
Low-Risk Group41.4
Intermediate-Risk Group41.0
High-Risk Group44.6

[back to top]

Rate of Local Disease Progression

Local failure was defined as the interval from end of RT to date of local failure (or combined local + distant failure). Competing events were distant failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval. (NCT00602667)
Timeframe: 1 year after completion of radiation therapy for last patient

InterventionPercentage of participants (Number)
Intermediate-risk Patients Who Received Focal Radiation13.2

[back to top]

Rate of Distant Disease Progression

Distant failure was defined as the interval from end of RT to date of distant failure (or combined local + distant failure). Competing events were local failure or second malignancy. Patients without an event were censored at date of last contact. The 1-year cumulative incidence was estimated and reported with a 95% confidence interval. (NCT00602667)
Timeframe: 1 year after completion of radiation therapy for last patient

Interventionpercentage of participants (Number)
Intermediate-risk Patients Who Received Focal Radiation25.6

[back to top]

Percentage of Patients With Objective Responses Rate to Induction Chemotherapy

For patients treated in the intermediate and high risk strata with residual or metastatic disease we will estimate the stratum-specific objective response rate (complete response (CR) or partial response [ PR]). All patients who receive at least 1 -dose of methotrexate are evaluable for response. Objective responses must be sustained for at least eight weeks. (NCT00602667)
Timeframe: From on-study date to 2 months after completion of induction chemotherapy (up to 4 months after on-study date)

InterventionPercentage of patients (Number)
Intermediate-Risk Group58.3
High-Risk Group21.1

[back to top]

Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients by DNA Methylation Subgroup

Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. Eligible medulloblastoma patients who received any methotrexate and had molecularly confirmed medulloblastoma are included in this analysis. Five patients were excluded as 3 had no archival tissue available and 2 were found to not be medulloblastoma by methylation profile. (NCT00602667)
Timeframe: From date on treatment to date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment

InterventionPercent Probability (Number)
Low-risk SHH Patients73.9
Intermediate-risk SHH Patients50.0
High-risk SHH Patients54.5
Intermediate-risk Group 3 Patients30.8
High-risk Group 3 Patients9.1
Intermediate-risk Group 4 Patients62.5
High-risk Group 4 Patients50.0

[back to top]

Percent Probability of Progression-free Survival (PFS) for Medulloblastoma Patients

Progression was defined as 25% increase in the size of any measurable lesion; the appearance of a new lesion; or the conversion of negative cerebrospinal fluid (CSF) cytology to positive. Defined as the time interval from date on treatment until the date of first progression, medulloblastoma-related death or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis. (NCT00602667)
Timeframe: From date on treatment until date of first progression or relapse or disease related death or date of last contact, estimated at 1 year after treatment

InterventionPercent Probability (Number)
Low-Risk Group73.9
Intermediate-Risk Group46.9
High-Risk Group30.8

[back to top]

Percent Probability of Event-free Survival (EFS) for Medulloblastoma Patients

Defined as the time interval from date on treatment until the date of first progression, second malignancy or death due to any cause; or date of last contact for patients who have not experienced an event. All eligible medulloblastoma patients who received any methotrexate are included in this analysis. (NCT00602667)
Timeframe: From date on treatment to date of first progression, relapse, second malignancy or death from any cause or to date of last contact, estimated at 1 year after

InterventionPercent Probability (Number)
Low-Risk Group73.9
Intermediate-Risk Group46.9
High-Risk Group30.8

[back to top]

Percent of PET Scans With Loss of Signal Intensity

Measures will be analyzed for intermediate risk participants who receive proton beam therapy (PBT) and who consent. This objective aims to assess the feasibility of using post-proton beam therapy (PBT) positron emission tomography (PET) as an in-vivo dosimetric and distal edge verification system in this patient population. To quantify the decay in signal, 134 scans from 53 patients were analyzed by recording the mean activation value (MAV), the average recorded PET signal from activation, within the target volume. With each patient being given the same dose, the percent standard deviation in the MAV can serve as a quantitative representation of signal loss due to radioactive decay. (NCT00602667)
Timeframe: Up to 3 times during RT consolidation

Interventionmean activation value (MAV) (Mean)
Intermediate Risk Group60

[back to top]

Percent of Patients With Sustained Objective Responses Rate After Consolidation

For patients enrolled on the high-risk arm with measurable residual disease after induction treated with consolidation therapy, we will estimate the objective response (complete response (CR)/partial response (PR)) rate after consolidation therapy with a 95% confidence interval. Objective responses must be sustained for at least eight weeks. All patients who receive at least 1 dose of cyclophosphamide or topotecan during consolidation are evaluable for response. (NCT00602667)
Timeframe: 8 weeks after completion of consolidation therapy (up to 8 months after on-study date)

Interventionpercentage of participants (Number)
High-Risk Group13.2

[back to top]

Participants With PK-guided Dosage Adjustment Achieving Target System Exposure of Intravenous Topotecan

Number of participants who successfully achieve target systemic exposure of intravenous topotecan after a pharmacokinetic-guided dosage adjustment during consolidation phase of therapy are reported. (NCT00602667)
Timeframe: Pre-infusion, 5 min., 1, and 3 hours from end of infusion

Interventionparticipants (Number)
Intermediate-Risk Group1
High-Risk Group20

[back to top]

Participants With Empirical Dosage Achieving Target System Exposure of Intravenous Topotecan

Number of participants who successfully achieve target systemic exposure of intravenous topotecan after an empiric dosage during consolidation phase of therapy are reported. (NCT00602667)
Timeframe: Pre-infusion, 5 min., 1, and 3 hours from end of infusion

Interventionparticipants (Number)
Intermediate-Risk Group0
High-Risk Group8

[back to top]

Overall Survival (OS) Compared to Historical Controls

OS was measured from the date of initial treatment to date of death or to date of last contact for survivors. 1-year OS estimates were reported by risk group. OS was compared to St. Jude historical cohorts by risk group using hazard ratios with 95% confidence intervals. (NCT00602667)
Timeframe: 1 year after treatment initiation of last patient

InterventionPercent probability (Number)
SJYC07 Low-risk Medulloblastoma Patients100
SJYC07 Intermediate-risk Medulloblastoma Patients84.4
SJYC07 High-risk Medulloblastoma Patients61.5

[back to top]

OSI-420 AUC0-24h

Erlotinib metabolite OSI-420 plasma concentration-time data are collected on day 1 of maintenance cycle B2. Individual estimates of OSI-420 AUC0-24h (area under concentration curve from 0 to 24 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-dose, 1, 2, 4, 8, and 24 hours post-dose

Interventionµmol·h/L (Median)
Low-Risk Group2.17
Intermediate-Risk Group1.81
High-Risk Group1.62

[back to top]

Methotrexate Volume of Central Compartment in Induction Cycle 4

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

InterventionL/m^2 (Median)
Low-Risk Group12.64
Intermediate-Risk Group13.31
High-Risk Group13.68

[back to top]

Methotrexate Volume of Central Compartment in Induction Cycle 3

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

InterventionL/m^2 (Median)
Low-Risk Group12.70
Intermediate-Risk Group13.55
High-Risk Group13.87

[back to top]

Methotrexate Volume of Central Compartment in Induction Cycle 2

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

InterventionL/m^2 (Median)
Low-Risk Group13.77
Intermediate-Risk Group13.73
High-Risk Group13.62

[back to top]

Methotrexate Volume of Central Compartment in Induction Cycle 1

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate volume of central compartment are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

InterventionL/m^2 (Median)
Low-Risk Group11.63
Intermediate-Risk Group13.70
High-Risk Group13.25

[back to top]

Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 4

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. (NCT00602667)
Timeframe: 42 hours from start of MTX

Interventionµmol/L (Median)
Low-Risk Group0.64
Intermediate-Risk Group0.64
High-Risk Group0.55

[back to top]

Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 3

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. (NCT00602667)
Timeframe: 42 hours from start of MTX

Interventionµmol/L (Median)
Low-Risk Group0.65
Intermediate-Risk Group0.70
High-Risk Group0.58

[back to top]

Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 2

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. (NCT00602667)
Timeframe: 42 hours from start of MTX

Interventionµmol/L (Median)
Low-Risk Group0.75
Intermediate-Risk Group0.72
High-Risk Group0.69

[back to top]

Methotrexate Concentration at 42 Hours Post-dose in Induction Cycle 1

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate concentration at 42 hours post-dose are obtained using post hoc analysis. (NCT00602667)
Timeframe: 42 hours from start of MTX

Interventionµmol/L (Median)
Low-Risk Group0.49
Intermediate-Risk Group0.57
High-Risk Group0.61

[back to top]

Methotrexate Clearance in Induction Cycle 4

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

InterventionL/h/m^2 (Median)
Low-Risk Group5.75
Intermediate-Risk Group5.89
High-Risk Group5.79

[back to top]

Methotrexate Clearance in Induction Cycle 3

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

InterventionL/h/m^2 (Median)
Low-Risk Group5.68
Intermediate-Risk Group5.78
High-Risk Group5.81

[back to top]

Methotrexate Clearance in Induction Cycle 2

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

InterventionL/h/m^2 (Median)
Low-Risk Group5.47
Intermediate-Risk Group5.70
High-Risk Group5.70

[back to top]

Methotrexate Clearance in Induction Cycle 1

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate clearance are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of Methotrexate (MTX)

InterventionL/h/m^2 (Median)
Low-Risk Group5.69
Intermediate-Risk Group6.06
High-Risk Group5.65

[back to top]

Methotrexate AUC0-66h in Induction Cycle 4

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 4. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

Interventionµmol·h/L (Median)
Low-Risk Group1804
Intermediate-Risk Group1841
High-Risk Group1886

[back to top]

Methotrexate AUC0-66h in Induction Cycle 3

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 3. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

Interventionµmol·h/L (Median)
Low-Risk Group1872
Intermediate-Risk Group1879
High-Risk Group1831

[back to top]

Methotrexate AUC0-66h in Induction Cycle 2

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 2. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

Interventionµmol·h/L (Median)
Low-Risk Group1900
Intermediate-Risk Group1902
High-Risk Group1879

[back to top]

Methotrexate AUC0-66h in Induction Cycle 1

Methotrexate plasma concentration-time data are collected after the start of methotrexate infusion in induction cycle 1. Population parameters and inter-subject variability are estimated. Individual estimates of methotrexate AUC0-66h (area under concentration curve from time 0 to 66 hours post-dose) are obtained using post hoc analysis. (NCT00602667)
Timeframe: Pre-infusion and 6, 23, 42, 66 hours from start of MTX

Interventionµmol·h/L (Median)
Low-Risk Group1797
Intermediate-Risk Group1813
High-Risk Group1821

[back to top]

Feasibility and Toxicity of Administering Vinblastine With Induction Chemotherapy for Patients With Metastatic Disease as Measured by the Percentage of Courses Delayed for More Than 7 Days Due to Toxicity

For the subset of patients with metastatic disease (high-risk group patients), during induction, the proportion percentage of courses during which subsequent chemotherapy administration was delayed for more than 7 days due to toxicity will be calculated. Patients were to receive 4 courses of induction and then consolidation chemotherapy. (NCT00602667)
Timeframe: From on-study date up to 4 months after on-study date

InterventionPercentage of courses delayed (Number)
High-Risk Group3.8

[back to top]

Number of Participants With Objective Response

Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. (NCT00603538)
Timeframe: Baseline up to 6 cycles (1 cycle = 21 days)

,,
Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)Objective Response (CR+PR)
CP-751,871 10 mg/kg in Combination With Chemotherapy Agents033
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents033
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents011

[back to top]

Area Under the Plasma Concentration Curve From Time Zero to Tau (AUCtau)

AUCtau: AUC from time zero to tau, the dosing interval, where tau is the actual time of the predose sampling for the next cycle. AUCtau was calculated using the linear/log trapezoidal method. (NCT00603538)
Timeframe: Cycle 4: prior to CP-751,871 (Day 1) dosing , and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Interventionmg*h/mL (Mean)
CP-751,871 6 mg/kg in Combination With Chemotherapy AgentsNA
CP-751,871 10 mg/kg in Combination With Chemotherapy AgentsNA
CP-751,871 20 mg/kg in Combination With Chemotherapy AgentsNA

[back to top]

Area Under the Plasma Concentration-time Curve From Time 0 to Day 22 (AUC0-day22)

AUC(0-day22) : AUC from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sampling for the next cycle. AUC(0-day22) was calculated using the linear/log trapezoidal method. (NCT00603538)
Timeframe: Cycle 1: prior CP-751,871 (Day 1) to dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Interventionmg*h/L (Mean)
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents22400
CP-751,871 10 mg/kg in Combination With Chemotherapy Agents36700
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents82700

[back to top]

Number of Participants With Positive Anti-Drug Antibody (ADA) Specific to CP-751,871 Following an Intravenous Infusion of CP-751,871.

The screening assay for anti-CP-751,871 antibodies was performed. (NCT00603538)
Timeframe: Day 1 of Cycles 1 (predose) and 4, and end of study

Interventionparticipants (Number)
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents0
CP-751,871 10 mg/kg in Combination With Chemotherapy Agents0
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents0

[back to top]

Observed Accumulation Ratio (Rac)

The ratio of Cycle 4 AUCtau to Cycle 1 AUCtau (NCT00603538)
Timeframe: Cycle 1 and Cycle 4: prior to CP-751,871 (Day 1) dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Interventionratio (Mean)
CP-751,871 6 mg/kg in Combination With Chemotherapy AgentsNA
CP-751,871 10 mg/kg in Combination With Chemotherapy AgentsNA
CP-751,871 20 mg/kg in Combination With Chemotherapy AgentsNA

[back to top]

Plasma Decay Half-Life (t1/2)

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. (NCT00603538)
Timeframe: Cycle 1 : prior to CP-751,871 (Day 1) dosing, and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

Interventionhours (Mean)
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents264
CP-751,871 10 mg/kg in Combination With Chemotherapy AgentsNA
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents248

[back to top]

Serum Concentrations of Total Insulin-like Growth Factor 1 (IGF-1)

IGF-1 is one of the IGF-axis related biomarkers. (NCT00603538)
Timeframe: Day 1 of Cycles 1 to 6, Day 8 of Cycles 1 to 4, and end of study

,,
Interventionng/L (Mean)
Cycle 1 Day 1 (n=6,7,6)Cycle 1 Day 8 (n=6,6,6)Cycle 2 Day 1 (n=6,5,6)Cycle 2 Day 8 (n=6,5,6)Cycle 3 Day 1 (n=5,4,6)Cycle 3 Day 8 (n=5,4,6)Cycle 4 Day 1 (n=4,4,5)Cycle 4 Day 8 (n=4,4,5)Cycle 5 Day 1 (n=2,2,2)Cycle 6 Day 1 (n=2,2,1)End of treatment (n=5,6,6)
CP-751,871 10 mg/kg in Combination With Chemotherapy Agents167.7611.7773.6819.8864.0765.5867.3904.8788.5927.0830.3
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents136.8493.8649.5544.7706.0698.0634.4749.0565.0695.0655.2
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents126.2518.3579.8709.0649.8774.2812.5784.5908.0835.0562.8

[back to top]

Serum Concentrations of Total Insulin-like Growth Factor Binding Protein-3 (IGF-BP-3)

IGF-BP3 is one of the IGF-axis related biomarkers. (NCT00603538)
Timeframe: Day 1 of Cycles 1-6, Day 8 of Cycles 1-4, and end of treatment

,,
Interventionmg/L (Mean)
Cycle 1 Day 1 (n=6,7,6)Cycle 1 Day 8 (n=6,6,6)Cycle 2 Day 1 (n=6,5,6)Cycle 2 Day 8 (n=6,5,6)Cycle 3 Day 1 (n=5,4,6)Cycle 3 Day 8 (n=5,4,6)Cycle 4 Day 1 (n=4,4,5)Cycle 4 Day 8 (n=4,4,5)Cycle 5 Day 1 (n=2,2,2)Cycle 6 Day 1 (n=2,2,1)End of treatment (n=5,6,6)
CP-751,871 10 mg/kg in Combination With Chemotherapy Agents2.264.205.686.266.785.935.184.955.356.855.93
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents2.553.855.254.635.075.304.324.443.903.204.63
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents2.384.355.126.536.084.665.135.103.455.754.66

[back to top]

Number of Participants With Dose Limiting Toxicities (DLT)

A DLT was defined as any one of the following adverse events observed in Cycle 1 which was considered as related to CP-751,871 combination therapy; 1) >=Grade 3 gastrointestinal toxicity, hyperglycemia and/or fatigue despite the use of adequate/optimal medical intervention, 2) Any other >=Grade 3 toxicity not classified under CTCAE blood/bone marrow, or 3) Grade 4 neutropenia that persisted for >=7 consecutive days or was complicated by fever (defined as a body temperature >38.0 Celsius degree), 4) Grade 3 thrombocytopenia which needed blood transfusion or Grade 4 thrombocytopenia. (NCT00603538)
Timeframe: Cycle 1

Interventionparticipants (Number)
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents1
CP-751,871 10 mg/kg in Combination With Chemotherapy Agents2
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents0

[back to top]

Maximum Observed Concentration (Cmax) of CP-751,871

(NCT00603538)
Timeframe: Cycles 1 and 4 at prior to dosing of CP-751,871 (Day 1), and 1, 24, 72 and 168 (Day 8) hours after end of CP-751,871 infusion

,,
Interventionmg/L (Mean)
Cycle 1 (n=6,6,6)Cycle 4 (n=4,4,5)
CP-751,871 10 mg/kg in Combination With Chemotherapy Agents197294
CP-751,871 20 mg/kg in Combination With Chemotherapy Agents485550
CP-751,871 6 mg/kg in Combination With Chemotherapy Agents113178

[back to top]

Progression Free Survival.

From randomization to the first documented disease progression or death from any cause, whichever came first, assessed until all participants randomized to the study have progressed for died. (NCT00603915)
Timeframe: From the on-study date until the date of first documented progression or date of death from any cause any cause until all participants have progressed or died.

InterventionMonths (Mean)
GEMCITABINE AND CISPLATIN/CARBOPLATIN (GC) PLUS ERLOTINIB6.3

[back to top]

Number of Participants With the Responses Outlined

"Complete Response (CR): disappearance of all clinical and radiological evidence of tumour.~Partial Response (PR): at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD.~Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.~Progressive Disease (PD): at least a 20% increase in the sum of LD of measured lesions taking as references the smallest sum LD recorded since the treatment started. Appearance of new lesions will also constitute progressive disease." (NCT00603915)
Timeframe: Measured every 2 cycles until the participant is off treatment.

InterventionParticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseInevaluable
GEMCITABINE AND CISPLATIN/CARBOPLATIN (GC) PLUS ERLOTINIB071111

[back to top]

Number of Months of Progression Free Survival (PFS)

The PFS is defined as the duration of time from the start of treatment to time of progression or death, whichever occurs first. (NCT00604461)
Timeframe: 2 Years, 9 Months

InterventionMonths (Median)
Dose Escalation Followed by Maintenance Therapy7.8

[back to top]

Number of Participants With Partial Response (PR) of Target Lesions

Tumor response was assessed in 12 patients who had at least one follow-up computed tomography (CT) scan. Response Evaluation Criteria in Solid Tumors (RECIST) definition of Partial Response: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (NCT00604461)
Timeframe: Up to 12 Months

Interventionparticipants (Number)
Dose Escalation Followed by Maintenance Therapy4

[back to top]

Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD40 PD0, PDmax

Assess activity of B cells in the presence of CP-870893. CD40 is a costimulatory protein and is a target for CP-870893. Measurement of CD40 on white blood cells provides a measure of target modulation by CP-870893. Higher numbers may indicate potential for increased activation of antigen presenting cells. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose

,,,,,
Interventionpercentage of cells (Mean)
PD0PDMAX
Schedule A - CP-870893 0.1 mg/kg99.2656.615
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)99.826711.7883
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)99.004313.6929
Schedule B - CP-870893 0.1 mg/kg99.98330.65
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)99.653318.9517
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)88.0712.6514

[back to top]

Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)

Any of the following during first cycle of treatment and attributable to CP-870893: Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for ≥7 days; Gr 3 or 4 febrile neutropenia (ANC <1000/mm^3, fever ≥38.5 degrees Celsius; platelets ≤25,000 cells/mm^3); ≥Gr 3 non-hematological adverse event despite optimal supportive care; ≥Gr 3 cytokine release syndrome or acute infusion reaction; failure to recover to Gr <1 toxicity after delaying next cycle by maximum of 2 weeks; Day 3 or 8 ANC <1000 cells/mm^3 or platelets <80000 cells/mm^3, or non-hematologic toxicity ≥Gr 2. (NCT00607048)
Timeframe: Schedule (Sch) A Cycle 1 / Day 3 or Schedule B Cycle 1 / Day 8 up to Cycle 1 / Day 21

Interventionparticipants (Number)
Schedule A - CP-870893 0.1 mg/kg0
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)1
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)0
Schedule B - CP-870893 0.1 mg/kg0
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)1
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)0

[back to top]

Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD19 Pre-dose Percentage (PD0), Maximum Post-dose Percentage (PDmax)

Assess activity of B cells (involved in production of antibodies) in presence of CP-870893. Clusters of differentiation (CD) are specific types of proteins on cell surface. CD19 is a B cell antigen receptor and is used to quantitate changes in proportion of B cells in peripheral blood as a consequence of therapy. Higher numbers may indicate a greater presence of CD19 on cell surface with increased potential for antigen response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose

,,,,,
Interventionpercentage of cells (Mean)
PD0PDMAX
Schedule A - CP-870893 0.1 mg/kg5.814.99
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)9.127.3017
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)11.32579.4614
Schedule B - CP-870893 0.1 mg/kg13.52336.7133
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)9.427.7783
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)6.55144.6786

[back to top]

Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD23 PD0, PDmax

Assess activity of B cells in the presence of CP-870893. CD23 is a low-affinity receptor that has a role in transportation in antibody feedback regulation. Agents that engage CD40 have been reported to increase CD23 expression; increased CD23 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate a potential for increased antibody response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose

,,,,,
Interventionpercentage of cells (Mean)
PD0PDMAX
Schedule A - CP-870893 0.1 mg/kg71.15522.155
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)86.226736.735
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)80.484320.0857
Schedule B - CP-870893 0.1 mg/kg90.23337.58
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)85.2622.3183
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)83.094333.3057

[back to top]

Change in Cytokine Concentrations of Tumor Necrosis Factor Alpha (TNF Alpha): CYTO0, CYTOMAX

Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose

,,,,,
Interventionpg/mL (Mean)
CYTO0CYTOMAX
Schedule A - CP-870893 0.1 mg/kg15.60155.73
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)15.60108.90
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)15.60113.11
Schedule B - CP-870893 0.1 mg/kg15.60212.73
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)15.60161.90
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)15.60675.34

[back to top]

Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD54 PD0, PDmax

Assess activity of B cells in presence of CP-870893. CD54 is an intercellular adhesion molecule. When activated, leukocytes bind to endothelial cells via CD54 and then transmigrate into tissues. Agents that engage CD40 have been reported to increase CD54 expression; increased CD54 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose

,,,,,
Interventionpercentage of cells (Mean)
PD0PDMAX
Schedule A - CP-870893 0.1 mg/kg95.73528.505
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)94.766725.85
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)97.948623.5229
Schedule B - CP-870893 0.1 mg/kg99.63671.7
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)96.486733.2017
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)94.557121.1886

[back to top]

Change in Bone Marrow Derived Cells (B Cell) Surface Markers: CD86 PD0, PDmax

Assess activity of B cells in presence of CP-870893. CD86 is a protein expressed on antigen-presenting cells and provides co-stimulatory signals for T cell (role in cell-modulated immunity) activation. Agents that engage CD40 have been reported to increase CD86 expression; increased CD86 expression may, therefore, serve as a marker for CD40 binding by CP-870893. Higher numbers may indicate potential for increased immune response. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose

,,,,,
Interventionpercentage of cells (Mean)
PD0PDMAX
Schedule A - CP-870893 0.1 mg/kg3.9112.795
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)5.816726.275
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)18.762911.9443
Schedule B - CP-870893 0.1 mg/kg5.536718.04
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)9.2328.0917
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)16.718634.3943

[back to top]

Change in Bone Marrow Derived Cells (B Cell) Surface Markers: Human Leukocyte Antigen (HLA-DR) PD0, PDmax

Assess activity of B cells in presence of CP-870893. HLA-DR is a component of the Major Histocompatibility Complex in humans and presents antigens for recognition by the immune system. Agents that engage CD40 have been reported to increase HLA-DR expression; increased HLA-DR expression may serve as a marker for CD40 binding by CP-870893. Positive values may indicate greater presence of cells associated with potential for antibody production. Percentage of cells reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, 6, 24, and 48 hours postdose

,,,,,
Interventionpercentage of cells (Mean)
PD0PDMAX
Schedule A - CP-870893 0.1 mg/kg98.2433.88
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)98.32527.4983
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)99.098621.7857
Schedule B - CP-870893 0.1 mg/kg99.78332.7833
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)97.415.1783
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)98.564327.0986

[back to top]

Change in Cytokine Concentrations of Interleukin 6 (IL 6): Pre-dose Concentration (CYTO0), Maximum Post-dose Concentration (CYTOMAX)

Concentrations reported as the mean of the pre-dose values and the mean of the maximum post-dose values to show change. An increase in values indicates greater cytokine release from cells targeted by the antibody and may be associated with an infusion reaction. (NCT00607048)
Timeframe: Schedule A Cycle 1 / Day 3 and Schedule B Cycle 1 / Day 8: predose, end of infusion, 1 , 2, 4, 6, 24, and 48 hours postdose

,,,,,
Interventionpicograms per milliliter (pg/mL) (Mean)
CYTO0CYTOMAX
Schedule A - CP-870893 0.1 mg/kg10.57120.67
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)12.10275.48
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)14.52371.22
Schedule B - CP-870893 0.1 mg/kg3.547113.45
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)41.34339.00
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)8.040679.40

[back to top]

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)

Area under the serum concentration time-curve from time zero to the last measured concentration. AUClast was estimated using non-compartmental methods on the sequence of sample measurements. Mean of individual observed AUClast values measured as nanograms multiplied by micrograms per milliliter (ng*mcg/mL). (NCT00607048)
Timeframe: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours post-dose up to a maximum of 8 cycles (6 months)

Interventionhr*mcg/mL (Mean)
Schedule A - CP-870893 0.1 mg/kg3.37
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)10.4
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)7.5
Schedule B - CP-870893 0.1 mg/kg1.35
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)13.0
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)5.71

[back to top]

Maximum Observed Serum Concentration (Cmax)

Mean of individual observed Cmax values measured as micrograms per milliliter (mcg/mL). (NCT00607048)
Timeframe: Schedule A Day 3 of each 21 Day Cycle, Schedule B Day 8 of each 21 Day Cycle: Pre-dose, 5 minutes after end of infusion, and 2, 6, and 24 hours (hrs) post-dose up to a maximum of 8 cycles (6 months)

Interventionmcg/mL (Mean)
Schedule A - CP-870893 0.1 mg/kg0.97
Schedule A - CP-870893 0.2 mg/kg (Escalation Cohort)1.51
Schedule A - CP-870893 0.2 mg/kg (Expansion Cohort)1.36
Schedule B - CP-870893 0.1 mg/kg0.61
Schedule B - CP-870893 0.2 mg/kg (Escalation Cohort)1.97
Schedule B - CP-870893 0.2 mg/kg (Expansion Cohort)1.06

[back to top]

Tumor Response of Partial Response (PR) and Complete Response CR) According to Response Evaluation Criteria in Solid Tumors (RECIST)

Number of participants with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR was defined as the disappearance of all target and nontarget lesions. PR was defined as a ≥30% decrease in the sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. (NCT00607048)
Timeframe: Schedule A and Schedule B: Baseline and Day 21 of every even numbered cycle up to a maximum of 8 cycles (6 months)

,
Interventionparticipants (Number)
Complete responsePartial response
Schedule A - CP-87089302
Schedule B - CP-87089303

[back to top]

Clinical Benefit Rate (CBR=CR+PR+SD)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT00608972)
Timeframe: up to two years

InterventionParticipants (Count of Participants)
Doxil, Carboplatin and Bevacizumab13

[back to top]

Median Overall Survival After Treatment With Doxil, Carboplatin and Bevacizumab in Patients With ER, PR, HER2neu Negative

median overall survival (NCT00608972)
Timeframe: From date of randomization up to two years

Interventionmonths (Median)
Doxil, Carboplatin and Bevacizumab11

[back to top]

One-year Progression-free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00608972)
Timeframe: one year

Interventionparticipants (Number)
Doxil, Carboplatin and Bevacizumab31

[back to top]

Progression Free Survival (PFS) After Treatment With Doxil, Carboplatin and Bevacizumab in Patients With ER, PR, HER2neu Negative Metastatic Breast Cancer

(NCT00608972)
Timeframe: Two Years

Interventionparticipants (Number)
Doxil, Carboplatin and Bevacizumab6

[back to top]

Six-month Survival After Treatment With Doxil, Carboplatin and Bevacizumab in Patients With ER, PR, HER2neu Negative

Six-month survival rate (NCT00608972)
Timeframe: six months

InterventionPercentage participants (Number)
Doxil, Carboplatin and Bevacizumab41.9

[back to top]

Progression-free Survival (PFS) as Evaluated by RECIST

Interval between date of randomization and earliest date of objective disease progression per RECIST criteria or death due to any cause in the absence of progression. Analysis was based on August 31, 2009 data cut-off (78 PFS events analysis) and was performed with patients in ITT analysis set who received AZD0530 175mg or Placebo 175mg. (NCT00610714)
Timeframe: Date of randomization to earliest date of objective disease progression or death due to any cause (conducted when a minimum of 78 progression free survival events had occurred)

InterventionMonths (Median)
AZD0530 , Paclitaxel , Carboplatin i.v.8.28
Carboplatin ,Paclitaxel7.79

[back to top]

Objective Response Rate as Evaluated by Response Evaluation Criteria In Solid Tumors ( RECIST)

Number of responders (complete (CR) or partial (PR) responders). CR = disappearance of all target lesions PR = 30% decrease in the sum of the longest diamete. Analysis was based on August 31, 2009 data cut-off , and was performed with patients who had measurable disease and received AZD0530 175mg or Placebo 175mg. (NCT00610714)
Timeframe: Response is evaluated from randomization to objective disease progression per RECIST criteria or death due to any cause in the absence of progression (conducted when a minimum of 78 progression free survival events had occurred)

InterventionParticipants (Number)
AZD0530 , Paclitaxel , Carboplatin i.v.47
Carboplatin ,Paclitaxel45

[back to top]

Overall Survival (Number of Deaths)

Interval between date of randomization and death due to any cause. Analysis was based on January 31, 2010 data cut-off and was performed with patients in ITT analysis set who received AZD0530 175mg or Placebo 175mg. At this time, data were still immature and median overall survival was not reached. Number of deaths is presented instead (NCT00610714)
Timeframe: Date of randomization to death due to any cause

InterventionParticipants (Number)
AZD0530 , Paclitaxel , Carboplatin i.v.12
Carboplatin ,Paclitaxel14

[back to top] [back to top]

Overall Survival.

Median survival time following treatment. (NCT00614484)
Timeframe: Monthly for duration of participant lifespan. Average lifespan 1-2 years

InterventionMonths (Median)
Chemothrapy and Proton Therapy15

[back to top]

Number of Participants With Complete and Partial Tumor Responses

A complete response (CR),was disappearance of all target lesions on CT scan and absence of appearance of any new lesion was required. Partial response (PR) was assessed by at least a 30% decrease in the sum of the longest diameter (LD) of target lesions without appearance of any new lesions. Progressive disease (PD) was defined as at least a 20% increase in the sum of the LD of target lesions or the appearance of one or more new lesions. Patients were assessed to have stable disease if neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD, without appearance of new lesions. Patients who received one or more cycles were evaluable for response. (NCT00614822)
Timeframe: Patients were enrolled over a 24 month period for treatment visits. After end of treatment visits, subjects were seen or contacted every 3 months for survival data. Median follow up was 49 weeks (6 weeks to death.

InterventionParticipants (Count of Participants)
Complete ResponsePartial Response
One Arm for Study127

[back to top]

Number of Participants With Adverse Events

Measured by adverse events such as grade 4 toxicities, hospitalizations for toxicities, fever and neutropenia events, and clinically significant bleeding/thrombotic events. (NCT00614822)
Timeframe: Subjects were seen or contacted every 3 months with medain follow up of 49 weeks.

InterventionParticipants (Count of Participants)
ThrombocytopeniaRespiratory distressGrade 3 diarrheafatigue
One Arm for Study1111

[back to top]

Progression Free Survival

"From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year)." (NCT00614822)
Timeframe: "From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year)."

Interventionweeks (Median)
Carboplatin, Bevacicumab, Premetrexed28

[back to top]

Overall Survival

Overal survival was defined as time between the date of treatment assignment and the date of death (NCT00614822)
Timeframe: "From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 year)."

Interventionweeks (Median)
One Arm for Study49

[back to top]

Number of Participants Who Experience Death During Treatment

(NCT00616967)
Timeframe: Up to 12 weeks

InterventionParticipants (Count of Participants)
Run-in Phase (Arm 0)0
Placebo (Arm I)0
Vorinostat (Arm II)0

[back to top]

Absolute Change From Baseline in Ki-67

(NCT00616967)
Timeframe: Change from baseline to Cycle 1-Day 15

Interventionpercent change in Ki-67 (Mean)
Responders7.0
Non-Responders12.0

[back to top]

Change in Standard Uptake Value (SULmax) From Baseline to Day 15 on FDG-PET

Change in standard uptake value (SULmax) as measured by percentage reduction of SULmax. The standard uptake value used for the PET analysis was SULmax, which is the standard uptake value normalized for lean body mass. (NCT00616967)
Timeframe: Baseline and day 15

Interventionpercentage reduction in SULmax (Median)
Responders63
Non-Responders32.9

[back to top]

Cumulative Methylation Index (CMI) at Day 15

(NCT00616967)
Timeframe: Day 15

InterventionCMI (Median)
Responders10
Non-Responders44

[back to top]

Change in Cumulative Methylation Index (CMI)

Change of CMI from baseline to Day 15 (D15), defined as log(D15 CMI + 1/baseline CMI + 1). The CMI was calculated as a sum of all gene-specific methylation indexes within a panel of 10 genes which included: HIST1H3C, AKR1B1, GPX7, HOXB4, TMEFF2, RASGRF2, COL6A2, ARHGEF7, TM6SF1, and RASSF1A. (NCT00616967)
Timeframe: Change from baseline to Day 15

InterventionCMI (Median)
Tissue CMI change from baselineSerum CMI change from baseline
Combined Arm I and Arm II140

[back to top]

Safety as Measured by Number of Participants Who Experience Adverse Events

Number of participants who experience adverse events as defined by NCI CTCAE version 3.0 (NCT00616967)
Timeframe: up to 30 days post-treatment

InterventionParticipants (Count of Participants)
Run-in Phase (Arm 0)6
Placebo (Arm 1)31
Vorinostat (Arm 2)31

[back to top]

Pathological Complete Response (pCR) Rate

The primary end point was pCR, defined as no viable invasive cancer in breast and axilla. All other cases were defined as non-pCR. The pCR rate was determined in each arm separately by performing an intent-to-treat (ITT) analysis of all randomized patients. Patients with unknown pCR status were considered non-responders. Computation of associated 90% confidence intervals did not account for the sequential design. (NCT00616967)
Timeframe: Time of breast cancer surgery

InterventionParticipants (Count of Participants)
Arm I9
Arm II8

[back to top]

Number of Participants With Clinical Complete Response (cCR)

cCR in the breast on physical is defined as the absence of any palpable abnormality on breast exam Iie: no skin or breast thickening, mass or associated skin or nipple changes) (NCT00616967)
Timeframe: 12 weeks

InterventionParticipants (Count of Participants)
Placebo (Arm I)16
Vorinostat (Arm II)15

[back to top]

Number of Patients With Complete Pathologic Response Rate, Observed Following Treatment With q3week Carboplatin, Weekly Abraxane and Weekly Trastuzumab in Resectable and Unresectable LABC;

These numbers represent patients with a RCB score of zero (0). RCB stands for residual cancer burden. (NCT00617942)
Timeframe: 1 year

Interventionparticipants (Number)
Cohort 112
Cohort 213

[back to top]

Patients Affected by Toxicities of Regimen During Treatment, Including Grade >2 Neurotoxicity the Incidence of Subclinical and Clinical Cardiac Toxicity

Please note that these events represent toxicities that were experienced during treatment, but that does not mean that all toxicities were indeed deemed related to study treatment. (NCT00617942)
Timeframe: 1 year

Interventionparticipants (Number)
Neo-adjuvant Cohort 137
Neo-adjuvant Cohort 223
Adjuvant Cohort 129
Adjuvant Cohort 219

[back to top]

Progression Free Survival

Progression is defined as a new lesion or a greater than or equal to 25% increase in the product of the largest perpendicular diameters of any one lesion on clinical exam or by ultrasound (U/S) or MRI. Analyzed using the Kaplan-Meier method. Cox proportional-hazards analysis will be used to derive the hazard ratio and 95% confidence interval between the two treatment arms, adjusted for clinical and demographic variables. (NCT00618657)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Arm I (HER-2 Positive)95
Arm II (HER-2 Negative)93

[back to top]

Number of Participants With Toxicity of the Combinations in HER2 Positive and HER2 Negative Breast Cancer Assessed Using the National Cancer Institute (NCI) Common Toxicity Criteria Version 3.0

The frequency of toxicities will be recorded. (NCT00618657)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Arm I (HER-2 Positive)19
Arm II (HER-2 Negative)50

[back to top]

Number of Participants With no Evidence of Microscopic pCR in the Neoadjuvant Setting

Defined as no evidence of microscopic invasive tumor at the primary tumor site in the surgical specimen. The 95% CI will be computed. (NCT00618657)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Arm I (HER-2 Positive)21
Arm II (HER-2 Negative)15

[back to top]

Overall Survival (OS)

The length of time from start of treatment that diagnosed patients remain alive. (NCT00618917)
Timeframe: Up to 5 years

Interventionmonths (Median)
Radiation + MnSOD PL + Paclitaxel + Carboplatin31

[back to top]

Overall (Objective) Response

Clinical Response per Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST v1.0: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) with reduction in short axis to <10 mm. Partial Response (PR): ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease: Neither sufficient shrinkage (compared to baseline) to qualify for partial or complete response (CR or PR) nor sufficient increase (taking as reference the smallest sum of diameters at baseline or while on study, whichever is smallest) to qualify for progressive disease (PD). Progressive Disease (PD): At least a 20%increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT00618917)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Partial Response per RECISTStable Disease per RECISTProgressive Disease per RECIST
MnSOD PL + Paclitaxel + Carboplatin322

[back to top]

Time to Disease Progression

The length of time from start of treatment until patients first disease recurrence/progression. Per RECIST v1.0: Progressive Disease (PD): At least a 20%increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT00618917)
Timeframe: Up to 5 years

Interventionmonths (Median)
Radiation + MnSOD PL + Paclitaxel + Carboplatin26

[back to top]

Radiation-induced Esophageal Toxicity

Number of patients experiencing grade III/IV esophageal toxicity per CTCAE v3.0. (NCT00618917)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Radiation + MnSOD PL + Paclitaxel + Carboplatin0

[back to top] [back to top]

Safety

Adverse Events occuring in >15% of patients (NCT00621049)
Timeframe: 2 years

,
Interventionparticipants (Number)
FatigueNauseaDiarrheaAnemiaNeutrophil count decreasedWhite blood cell decreasedAlopeciaPainPlatelet count decreasedConstipationDyspneaAnorexiaHyperglycemiaDysgeusiaMucositisVomitingCoughPeripheral sensory neuropathy
Docetaxel and Carboplatin4136242826272115201817181114121382
Docetaxel/Carboplatin/Bevacizumab/Erlotinib373226182018212313141412181212101215

[back to top]

Overall Survival (OS)

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death (NCT00621049)
Timeframe: 18 months

Interventionmonths (Median)
Docetaxel/Carboplatin/Bevacizumab/ErlotinibNA
Docetaxel and CarboplatinNA

[back to top]

Disease-free Survival

The length of time, in months, that patients were alive from the end of their treatment without any signs or symptoms of their disease. (NCT00621049)
Timeframe: 1 year

Interventionmonths (Median)
Docetaxel/Carboplatin/Bevacizumab/ErlotinibNA
Docetaxel and Carboplatin55.1

[back to top]

2-year Survival

Proportion of patients known to still be alive 2 years after coming on study (NCT00621049)
Timeframe: 24 months

Interventionpercentage of participants (Number)
Docetaxel/Carboplatin/Bevacizumab/Erlotinib78.2
Docetaxel and Carboplatin71.9

[back to top]

Tumor Response Rate, Calculated as a Percentage Along With it's 95% Confidence Interval

"A confirmed tumor response is defined to be a Complete Response or Partial Response noted~> as the objective status on 2 consecutive evaluations at least 8~> weeks apart. The proportion of tumor responses will be~> estimated by the number of confirmed tumor responses divided~> by the total number of evaluable patients.~> Complete Response (CR): Disappearance of all target lesions~> Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.~> Progression (PD): At least a 20% increase in the sum of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.~> Stable Disease (SD): Neither sufficient shrinkage to Qualify for PR nor sufficient increase to Qualify for PD taking as reference the smallest sum LD. responses will be calculated assuming that the number of~> confirmed tumor responses follows a binomial distribution." (NCT00626405)
Timeframe: Up to 5 years

Interventionpercentage of patients with response (Number)
Arm I23.8
Arm II33.3

[back to top]

Progression-free Survival at 6 Months

The primary endpoint is the 6 month post registration Progression-free survival (PFS) rate. Progression-free survival time is defined as the time from registration to documentation of disease progression using the RECIST criteria. Patients who died without documentation of disease progression will be considered to have progressed at death unless there is sufficient documented evidence to conclude no progression occurred prior to death. All patients, who meet the eligibility criteria, sign a consent form, and start treatment will be included in the evaluation of the 6 month PFS rate. (NCT00626405)
Timeframe: at 6 months

Intervention% of patients alive and progression free (Number)
Arm I32.8
Arm II56.1

[back to top]

Overall Survival

Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. (NCT00626405)
Timeframe: Up to 5 years

InterventionMonths (Median)
Arm I12.3
Arm II13.9

[back to top]

Overall Survival Time

Overall survival time is defined as the time between a patient's registration and death or end of survival follow up. (NCT00632853)
Timeframe: 11.25 years

InterventionMonths (Median)
Arm A28.7
Arm B30.5
Arm C32.3

[back to top]

The Rate of Treatment Failure

"The definition of treatment failure will include:~≥ 5% leukemic blasts at the time of pre-consolidation marrow~Death during/following induction chemotherapy (pre-consolidation)~Persisting marrow hypoplasia and pancytopenia for ≥ 2 months after chemotherapy~CNS or extramedullary disease at the time of pre-consolidation~Leukemia persistence after completion of induction treatment. Leukemia persistence is defined as greater than 10% residual blasts on marrow biopsy done 5-7 days after completion of induction chemotherapy" (NCT00634244)
Timeframe: Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration.

Interventionproportion of participants (Number)
Arm A (Carboplatin+Topotecan Hydrochloride)0.86
Arm B (Alvocidib+Cytarabine+Mitoxantrone)0.72
Arm C (Sirolimus+Mitoxantrone+Etoposide+Cytarabine)0.84

[back to top]

The Rate of Complete Remission (CR+CRi)

CR requires: 1. peripheral blood counts: neutrophil count ≥ 1.0 x 10^9/L, platelet count ≥ 100 x 10^9/L, reduced hemoglobin concentration or hematocrit has no bearing on remission status, and leukemic blasts must not be present in the peripheral blood. 2. bone marrow aspirate and biopsy: maturation of all cell lines must be present, ≤ 5% blasts, auer rods must not be detectable. 3. extramedullary leukemia, such as central nervous system (CNS) or soft tissue involvement, must not be present. CRi requires that all criteria for complete remission be satisfied except patients can have residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L). (NCT00634244)
Timeframe: Assessed every 3 months for the first 2 years and then every 6 months until relapse or death up to 3 years from registration.

Interventionproportion of participants (Number)
Arm A (Carboplatin+Topotecan Hydrochloride)0.143
Arm B (Alvocidib+Cytarabine+Mitoxantrone)0.278
Arm C (Sirolimus+Mitoxantrone+Etoposide+Cytarabine)0.15

[back to top]

6 Month Survival Rate

The percentage of participants surviving at least six months after baseline (NCT00642759)
Timeframe: 6 months

Interventionpercentage of participants surviving (Number)
Chemotherapy83

[back to top]

Objective Response Rate to Carboplatin, Abraxane and Avastin

Objective response rate to carboplatin, Abraxane and Avastin according to Response Evaluation Criteria in Solid Tumors [Version 1.0] (NCT00642759)
Timeframe: 3 years

InterventionParticipants (Count of Participants)
Partial ResponseStable DiseaseProgressive DiseaseNot Evaluable for Response
Chemotherapy131328

[back to top]

Overall Survival

The median overall survival in months (NCT00642759)
Timeframe: 3 years

InterventionMonths (Median)
Chemotherapy13.7

[back to top]

6-month Progression Free Survival Rate

Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00642759)
Timeframe: 6 Months

Interventionpercentage of participants (Number)
Chemotherapy74

[back to top]

Mean Urine Excretion of MK-1775 24 Hours After the Day 1 Monotherapy Dose

The mean cumulative amount of MK-1775 excreted unchanged in urine after a single oral dose was measured during the initial monotherapy cycle of the study. For this outcome measure, samples were collected and analyzed only for the MK-1775 monotherapy arms of the study at defined intervals after the Day 1 dose of monotherapy. Part 2 MK-1775 combination arms were not sampled per protocol. (NCT00648648)
Timeframe: At 0-4 hours, 4-8 hours, and 12-24 hours post Day 1 dose of monotherapy

Interventionmg (Mean)
MK-1775 325 mg Single Dose16.7
MK-1775 650 mg Single Dose35.4
MK-1775 1300 mg Single Dose154

[back to top]

Percentage of Total pCDC2 in Skin Cells at Baseline and 48 Hours After MK-1775 Dosing

The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and at 48 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 (150 mg, 200 mg, 250) BID x 2.5 Multi Dose plus cisplatin 75 mg/m^2 groups and the 325 mg BID x2.5 Multi Dose + Carboplatin group with available data per protocol. (NCT00648648)
Timeframe: Baseline, 48 hours after first MK-1775 dose

,,,
Interventionpercentage of cells (Geometric Least Squares Mean)
Baseline percentagePercentage after dosing
MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^228.615.7
MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^231.57.4
MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^231.511.1
MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 533.515.1

[back to top]

Percentage of Total pCDC2 in Skin Cells at Baseline and 24 Hours After MK-1775 Dosing

The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total pCDC2 at baseline and 24 hours after MK-1775 dosing were reported for participants in the Part 2-B/3 MK-1775 QD x2 Multi Dose plus Gemcitabine treatment groups with available data per protocol. (NCT00648648)
Timeframe: Baseline, 24 hours after first MK-1775 dose

,,,
Interventionpercentage of cells (Geometric Least Squares Mean)
Baseline percentagePercentage after dosing
MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^247.529.9
MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^227.917.7
MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^218.712.7
MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^211.66.3

[back to top]

Percentage of Total Cyclin-dependent Kinase (CDC2)-Positive Cells That Were Phosphorylated (pCDC2) in Skin Cells at Baseline and 8 Hours After MK-1775 Dosing

The pCDC2 level in skin cells was used as a marker to evaluate MK-1775 activity. Analysis was done by immunohistochemistry and the percentage of total CDC2-positive cells that were pCDC2 positive (% pCDC2-positive cells) at baseline and 8 hours after MK-1775 dosing were reported for participants in Part 1, 2-A, and 2-B/3 treatment groups with available data per protocol. (NCT00648648)
Timeframe: Baseline, 8 hours after first MK-1775 dose

,,,,,,,,,,,,,,,,,,
Interventionpercentage of cells (Geometric Least Squares Mean)
Baseline percentagePercentage after dosing
MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^224.114.4
MK-1775 100 mg Single Dose + Carboplatin AUC 534.441.9
MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^216.114.8
MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^253.228.9
MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^221.419.9
MK-1775 1300 mg Single Dose36.220.6
MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 52716.8
MK-1775 200 mg Single Dose + Carboplatin AUC 517.620.9
MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^228.622.1
MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^240.735.7
MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 52111.5
MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^228.120.1
MK-1775 325 mg Single Dose40.818
MK-1775 325 mg Single Dose + Carboplatin AUC 522.417.1
MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^230.816.6
MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^216.417.8
MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^218.313.7
MK-1775 650 mg Single Dose35.113.4
MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 515.712.1

[back to top]

Best Overall Response as Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

Best overall response achieved by a participant. Starting at Day 1, participants in Part 2 were evaluated for tumor response every 6-8 weeks until discontinuation from study treatment according to RECIST criteria; which are based on radiographic imaging. Recorded responses were either confirmed by Central Review or unconfirmed (Investigator assessment only), and included complete response (CR; defined as disappearance of all target lesions), partial response (PR; at least a 30% decrease in the sum of the longest diameter [LD] of target lesions, taking as reference the baseline sum LD), stable disease (SD; neither sufficient shrinkage to qualify for PR nor sufficient growth to qualify for PD, taking as reference the smallest sum LD since the treatment started), or progressive disease (PD; ≥20% increase in sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions). (NCT00648648)
Timeframe: From Day 1 up through discontinuation of study treatment (up to ~11.2 months)

,,,,,,,,,,,,,,,,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
CRConfirmed PRUnconfirmed PRSDPDNE
MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2020120
MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2000220
MK-1775 100 mg Single Dose + Carboplatin AUC 5000030
MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2001020
MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2010311
MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2000140
MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2000220
MK-1775 1300 mg Single Dose000000
MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5000310
MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2002440
MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2000820
MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2011830
MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2011630
MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2001310
MK-1775 200 mg Single Dose + Carboplatin AUC 5000030
MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2010710
MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2000510
MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 50021480
MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^2000410
MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2001210
MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 5000660
MK-1775 325 mg Single Dose000000
MK-1775 325 mg Single Dose + Carboplatin AUC 5011331
MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2000410
MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2000210
MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2000450
MK-1775 650 mg Single Dose000000
MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5000220

[back to top]

Plasma Concentration of MK-1775 at 8 Hours After Administration (C8hr) of Single or Multiple Oral Doses

MK-1775 was measured in the plasma at 8 hours after dosing (Day 1 for single dose of monotherapy, Day 2 of single-dose combination therapy and QD x 2 Combination dosing, and Day 3 dose for BID X 2.5 combination dosing) for participants with available data. (NCT00648648)
Timeframe: 8 hours after MK-1775 dose

InterventionnM (Mean)
MK-1775 325 mg Single Dose585
MK-1775 650 mg Single Dose1130
MK-1775 1300 mg Single Dose2190
MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^2129
MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^2235
MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^2108
MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^2310
MK-1775 100 mg Single Dose + Carboplatin AUC 5119
MK-1775 200 mg Single Dose + Carboplatin AUC 5262
MK-1775 325 mg Single Dose + Carboplatin AUC 5425
MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^241.7
MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^265.4
MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^2138
MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2188
MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2241
MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^2355
MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2346
MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^2407
MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2113
MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2388
MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2748
MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^2920
MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^21070
MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^22010
MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 5184
MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 5295
MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 5985
MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 51960

[back to top]

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)

DLTs were adverse events (AEs) considered at least possibly related to study drug that prevented escalation of the drug dose. Hematologic DLTs were any grade (Gr) 4-5 toxicity EXCEPT: Gr 4 anemia and Gr 4 leukopenia, Gr 4 neutropenia lasting for <7 days, Gr 4 thrombocytopenia lasting for <4 days except if a platelet transfusion is required, and Gr 3/Gr 4 neutropenia with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment. Non-hematologic DLT was defined as any Gr 3, 4, or 5 non-hematologic toxicity EXCEPT: nausea, vomiting, diarrhea, or dehydration (all Gr 3) occurring in a setting of inadequate compliance with supportive care measures and lasting for <48 hours, alopecia of any grade, inadequately treated hypersensitivity reactions, and clinically non-significant, treatable or reversible lab abnormalities including liver function tests, uric acid, etc. (NCT00648648)
Timeframe: Part 1: Up to 14 days, Part 2: Up to 28 days

InterventionParticipants (Count of Participants)
MK-1775 325 mg Single Dose0
MK-1775 650 mg Single Dose0
MK-1775 1300 mg Single Dose0
MK-1775 100 mg Single Dose + Gemcitabine 1000 mg/m^20
MK-1775 200 mg Single Dose + Gemcitabine 1000 mg/m^22
MK-1775 100 mg Single Dose + Cisplatin 75 mg/ m^20
MK-1775 200 mg Single Dose + Cisplatin 75 mg/ m^22
MK-1775 100 mg Single Dose + Carboplatin AUC 50
MK-1775 200 mg Single Dose + Carboplatin AUC 50
MK-1775 325 mg Single Dose + Carboplatin AUC 50
MK-1775 25 mg BID x2.5 Multi Dose + Gemcitabine 1000 mg/ m^21
MK-1775 50/25 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^22
MK-1775 50 mg BID x2.5 Multi + Gemcitabine 1000 mg/ m^25
MK-1775 100 mg QD x2 Multi + Gemcitabine 1000 mg/ m^20
MK-1775 125 mg QD x2 Multi + Gemcitabine 1000 mg/ m^20
MK-1775 150 mg QD x2 Multi + Gemcitabine 1000 mg/ m^22
MK-1775 175 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^21
MK-1775 200 mg QD x2 Multi Dose + Gemcitabine 1000 mg/ m^23
MK-1775 50 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^20
MK-1775 100 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^21
MK-1775 125 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^20
MK-1775 150 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^20
MK-1775 200 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^24
MK-1775 250 mg BID x2.5 Multi Dose + Cisplatin 75 mg/ m^23
MK-1775 75 mg BID x2.5 Multi Dose + Carboplatin AUC 50
MK-1775 150 mg BID x 2.5 Multi Dose + Carboplatin AUC 50
MK-1775 225 mg BID x2.5 Multi Dose + Carboplatin AUC 57
MK-1775 325 mg BID x2.5 Multi Dose + Carboplatin AUC 56

[back to top]

Overall Survival (OS)

Estimated 4-year survival, where survival is calculated as the time from study enrollment to death from any cause or last follow-up alive whichever occurs first. Kaplan-Meier method is used for estimation. Patients alive at last contact are censored. (NCT00653068)
Timeframe: Up to 4 years after study enrollment

InterventionEstimated Probability (Number)
Stratum I0.3888
Stratum III0.5486

[back to top]

Toxic Death

The number of patients who experience death that is considered to be primarily attributable to complications of treatment. (NCT00653068)
Timeframe: During and after completion of study treatment up to 1 year after enrollment.

InterventionParticipants (Count of Participants)
Stratum I3
Stratum III1

[back to top]

Non-hematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy

Number of Participants with Nonhematological Toxicity Associated With Chemotherapy: Grade 3 or Higher During Protocol Therapy. (NCT00653068)
Timeframe: During protocol therapy up to 1 year after enrollment.

InterventionParticipants (Count of Participants)
AcidosisAcute kidney injuryApneaAdult respiratory distress syndromeAspirationAtelectasisCatheter related infectionCentral nervous system necrosisDehydrationDiarrheaDissmeminated intravascular coagulation (DIC)EnterocolitisFebrile neutropeniaHearing impairmentHematuriaHydrocephalusHypernatremiaHypoalbuminemiaHypocalcemiaHypoglycemiaHypokalemiaHyponatremiaHypophosphatemiaHypotensionHypoxiaIncreased Alanine aminotransferaseIncreased Aspartate aminotransferaseIncreased LipaseIntracranial hemorrhagentraoperative venous injuryLaryngospasmLeft ventricular systolic dysfunctionLung infectionMulti-organ failureMucositis oralPoisoning and procedural complicationsOther gastrointestinal disordersOther infectionPneumonitisProductive coughPulmonary edemaRecurrent laryngeal nerve palsyRenal calculiRespiratory failureSeizureSepsisSinus tachycardiaStridorUpper respiratory infectionVascular access complicationVoice alterationVomitingWeight loss
All Patients11213121111161111132922465412111313117211113262211111

[back to top]

Event-free Survival

Estimated 4-year EFS where EFS is calculated as the time from study enrollment to disease progression, disease relapse, occurrence of a second malignant neoplasm, death from any cause or last follow-up whichever occurs first. Kaplan-Meier method is used for estimation. Patients without an event are censored at last contact. (NCT00653068)
Timeframe: Up to 4 years after study enrollment

InterventionEstimated probability (Number)
Stratum I0.3401
Stratum III0.4500

[back to top]

Chemistry NCI-CTCAE Toxicity Grade of 3 or 4 (Safety Population)

(NCT00653939)
Timeframe: Days 1 (pretreatment) per 21-day Cycle (6 Cycles)

,
Interventionparticipants (Number)
ALT - Grade 3ALT - Grade 4AST - Grade 3AST - Grade 4ALP - Grade 3ALP - Grade 4Total Bilirubin - Grade 3Total Bilirubin - Grade 4Glucose - Grade 3Glucose - Grade 4Creatinine - Grade 3Creatinine - Grade 4Calcium - Grade 3Calcium - Grade 4Magnesium - Grade 3Magnesium - Grade 4Phosphorus - Grade 3Phosphorus - Grade 4Potassium - Grade 3Potassium - Grade 4Sodium - Grade 3Sodium - Grade 4
Arm 1: Chemotherapy+Bevacizumab1000000001013122005150
Arm 2: Active Comparator+Fosbretabulin1010000000010111100020

[back to top]

Overall Survival (OS) Using a Multivariate Cox Regression Model in the Intent-to-Treat Population

(NCT00653939)
Timeframe: Until death or lost to follow-up, up to 12 months since randomization

InterventionMonths (Median)
Arm 1: Chemotherapy+Bevacizumab16.2
Arm 2: Active Comparator+Fosbretabulin13.6

[back to top]

Best Overall Tumor Response Rate (RR) in the Intent-to-Treat Population

Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 for target lesions (assessed by MRI or CT scan): Complete Response (CR) is defined as the disappearance of all target lesions, Partial Response (PR) is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, Progressive Disease is defined as at least 20% increase in the sum of the longest diameter of target lesions, Stable Disease (SD) is defined as neither shrinkage to qualify for a PR or increase to qualify for a PD. (NCT00653939)
Timeframe: Six 21-day cycles

,
Interventionparticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseUnknown
Arm 1: Chemotherapy+Bevacizumab0111334
Arm 2: Active Comparator+Fosbretabulin018815

[back to top]

Progression Free Survival (PFS) in the Intent-to-Treat Population

Progression was defined using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0. Based on 20% increase of the longest diameter of target lesions or appearance of one or more new non-target lesions or/and progression of non-target lesions since the treatment started. (NCT00653939)
Timeframe: Six 21-day cycles

Interventionmonths (Median)
Arm 1: Chemotherapy+Bevacizumab9.3
Arm 2: Active Comparator+Fosbretabulin8.6

[back to top]

Hematology NCI-CTCAE Grade 3 or 4 (Safety Population)

(NCT00653939)
Timeframe: Days 1 (pretreatment), 7, 14, and 21 per 21-day Cycle (6 Cycles)

,
Interventionparticipants (Number)
Hemoglobin - Grade 3Hemoglobin - Grade 4White Blood Cell - Grade 3White Blood Cell - Grade 4Absolute Neutrophils - Grade 3Absolute Neutrophils - Grade 4Platelets - Grade 3Platelets - Grade 4
Arm 1: Chemotherapy+Bevacizumab7414242036
Arm 2: Active Comparator+Fosbretabulin0112152053

[back to top]

Coagulation NCI-CTCAE Grade 3 or 4 (Safety Population)

(NCT00653939)
Timeframe: Day 1 (pretreatment) per 21-day Cycle (6 Cycles)

,
Interventionparticipants (Number)
INR - Grade 3INR - Grade 4PTT - Grade 3PTT - Grade 4
Arm 1: Chemotherapy+Bevacizumab2030
Arm 2: Active Comparator+Fosbretabulin3050

[back to top]

Response Rate at End of Treatment

Response to treatment was recorded 30 months following treatment initiation. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); PD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions . (NCT00654836)
Timeframe: 30 Months

Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Undetermined
Carboplatin, ABI-007 and Bevacizumab224312

[back to top]

Progression-free Survival

Progression-free survival was measured from treatment initiation to 30 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00654836)
Timeframe: 30 Months

InterventionMonths (Median)
Carboplatin, ABI-007 and Bevacizumab16

[back to top]

Overall Survival

Overall survival was measured from treatment initiation to 80 months (NCT00654836)
Timeframe: 80 Months

InterventionMonths (Median)
Carboplatin, ABI-007 and Bevacizumab21

[back to top]

Response Rate (Confirmed and Unconfirmed, Complete and Partial Response) in a Subset of Patients With Measurable Disease

"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI:~Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR." (NCT00661193)
Timeframe: From date of registration to 3 years or death, whichever comes first

Interventionparticipants (Number)
Erlotinib Hydrochloride2
Erlotinib Hydrochloride, Paclitaxel, Carboplatin6

[back to top]

Selection of One of Two Treatment Regimens (Erlotinib Hydrochloride With or Without Carboplatin and Paclitaxel) for Further Study in a Phase III Trial, Based on Median Progression-free Survival for ≥ 3 Months

(NCT00661193)
Timeframe: From date of registration to 3 years or death, whichever comes first

Interventionmonths (Median)
Erlotinib Hydrochloride1.6
Erlotinib Hydrochloride, Paclitaxel, Carboplatin4.6

[back to top]

Overall Response Rate

"Patient response to treatment per RECIST:~Progressive disease (PD): >=20% increase in sum of longest diameter (LD) of target lesion(s), taking as reference smallest sum LD recorded since treatment started Complete response (CR): disappearance of all target lesions Partial response (PR): >=30% decrease in sum of LD of target lesion(s), taking as reference baseline sum LD Stable disease (SD): neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD" (NCT00664105)
Timeframe: on-study date to date of best response

Interventionparticipants (Number)
Complete ResponsePartial ResponseProgressive DiseaseStable Disease
Chemo-radio Therapy633513

[back to top]

Overall Survival

Months from on-study to expired/last date known alive. (NCT00664105)
Timeframe: 14.95 months (average duration, on study date to off-study date)

InterventionMonths (Median)
Chemo-radio Therapy11

[back to top]

Time to Disease Progression

Time to disease progression in months (NCT00664105)
Timeframe: on-study date to date of progression

InterventionMonths (Median)
Chemo-radio Therapy5

[back to top]

Number of Participants With Adverse Events by Grade

Number of participants with adverse events, according to grade of event, using the NCI Common Toxicity Criteria (version 2.0) grading system to assign a grade to each event with 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, and 5 = death related to adverse event (NCT00664105)
Timeframe: 30 days after last treatment.

Interventionparticipants (Number)
Grade 1Grade 2Grade 3Grade 4Grade 5
Chemo-radio Therapy111935123

[back to top]

Number of Patients With Pathologic Complete Response (pCR)

pCR was defined as the absence of viable invasive tumor cells in the surgical breast specimen and axillary lymph nodes. (NCT00675259)
Timeframe: every 4 weeks

Interventionpatients (Number)
Neoadjuvant, Surgery, Adjuvant6

[back to top]

Evaluation of Dynamic Contrast-enhanced Magnetic Resonance Imaging in Assessing pCR at Baseline and After 2 Cycles of Neoadjuvant Therapy

Relative angiogenic volume (AV) was defined as the ratio of AV to the geometric volume of the tumor in the breast. (NCT00675259)
Timeframe: after 2 cycles of therapy

Interventionratio (Mean)
Baseline DCE-MRIRelative AV at end of cycle 2
Neoadjuvant, Surgery, Adjuvant0.65.4

[back to top]

Overall Expression of LZTS1 Before and After Neoadjuvant Therapy as Assessed by Immunohistochemistry

LZTS1 expression in breast cancer cells collected prior to NCT (NCT00675259)
Timeframe: prior to surgery

,,
Interventionpatients (Number)
0+1+2+3
Patients With Hormone-responsive BC6226
Patients With pCR2021
Patients With TNBC2036

[back to top]

Side Effects of Weekly Nab-paclitaxel, Carboplatin and Bevacizumab

Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0 (NCT00675259)
Timeframe: Up to 4 weeks

Interventionpatients (Number)
hypersensitivity reactionhypertensioninfection at mastectomy site
Adjuvant Bevacizumab121

[back to top]

Number of Participants With Dose-limiting Toxicity (DLT)

DLT is defined as any of the following: Common Terminology Criteria (CTC), Version 3, Grade(Gr) 4 neutropenia (absolute neutrophil count <500 cells/mm^3) for at least 5 days or febrile neutropenia; Gr 4 thrombocytopenia (<25,000 cells/mm^3 or bleeding needing platelet transfusion); Gr 3 or 4 nausea, vomiting, or diarrhea, despite medical intervention; any other drug-related Gr 3 or 4 nonhematologic toxicity, except Gr 3 injection site reaction, fatigue/asthenia, transient arthralgia/myalgia, or transient electrolytes abnormal. Gr 1=Mild; Gr 2=Moderate; Gr 3=Severe; Gr 4=Life-threatening. (NCT00683904)
Timeframe: Days 1 through 21 (Cycle 1)

InterventionParticipants (Number)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL0
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL1

[back to top]

Number of Participants at Each Response Evaluation Criteria in Solid Tumors (RECIST) Assessment

Tumor response was assessed using the RECIST assessment: Complete response (CR)=Disappearance of all clinical and radiologic evidence of target lesions; Partial response (PR)=At least 30% reduction in the sum of the longest diameters of all target lesions; Progressive disease (PD)=At least 20% increase in the sum of the longest diameters of all target lesions; Stable disease (SD)=Neither PR nor PD criteria were met. (NCT00683904)
Timeframe: Days 1 through 21 (Cycle 1)

,
InterventionParticipants (Number)
CRPRPDSDUnable to be assessed (patient discontinuation)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL02200
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL01041

[back to top] [back to top]

Maximum Observed Plasma Concentration of Ixabepilone

(NCT00683904)
Timeframe: Days 1 to 8 of Cycle 1 (21 days)

Interventionng/mL (Geometric Mean)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL195.77
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL250.32

[back to top]

Area Under the Plasma Concentration-time Curve (AUC) From Time Zero Extrapolated to Infinite Time of Ixabepilone

(NCT00683904)
Timeframe: Days 1 to 8 of Cycle 1 (21 days)

Interventionng*h/mL (Geometric Mean)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL1542.11
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL2135.93

[back to top] [back to top] [back to top]

Number of Participants With Abnormalities in Blood Pressure and Heart Rate

Blood pressure and heart rate obtained before ixabepilone infusion, every 1 hour during and at the end of ixabepilone infusion, and at the end of carboplatin infusion in Cycle 1. For subsequent cycles, vital signs obtained before ixabepilone infusion, at the end of ixabepilone infusion, and at the end of carboplatin infusion. Any new or worsening clinically significant changes since last entry were recorded as appropriate AE or SAE. (NCT00683904)
Timeframe: At screening and Day 1 of Cycle 1 (21 days) and Day 1 of Cycle 2 (Study day 22)

,
InterventionParticipants (Number)
Blood pressureHeart rate
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL00
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL00

[back to top]

Number of Participants With Abnormalities in Weight and Eastern Cooperative Oncology Group (ECOG) Performance Status

Participants weighed same day as serum chemistry tests. Body surface area recalculated only if body weight changes >10%. ECOG criteria used to assess disease progression and affects on daily living abilities and to determine appropriate treatment and prognosis. Grade 1=Restricted physical activity but ambulatory and capable of light work; Grade 2=Ambulatory, capable of self care, but unable to carry out any work activities; Grade 3=Capable of limited self care, confined to bed or chair 50% or more of waking hours; Grade 4=Completely disabled, totally confined to bed or chair. (NCT00683904)
Timeframe: At screening of Cycle 1 (21 days) and Day 1 of Cycle 2 (Study day 22)

,
InterventionParticipants (Number)
Blood pressureHeart rateWeightECOG performance status
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL0000
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL0000

[back to top]

Number of Participants With Abnormalities in Urine Testing Results by Worst CTC Grade

Toxicities graded according to CTC, Version 3. Protein Gr 1: <1.0 g/24 hrs (1+); Gr 2: 1.0 to 3.4 g/24 hrs (2+ to 3+ ); Gr 3: >=3.5 g/24 hrs (4+); Gr 4: Nephrotic syndrome. Note: + = qualitative measure of urine chemistry. (NCT00683904)
Timeframe: At screening and Days 8 and 15 of Cycle 1 (21 days)

,
InterventionParticipants (Number)
Protein (Grade 1)Protein (Grade 2)Protein (Grade 3)Protein (Grade 4)Not reported
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL23000
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL20000

[back to top]

Number of Participants With Abnormalities in Serum Chemistry Laboratory Values by Worst CTC Grade

ULN=upper limit of normal; LLN=lower limit of normal. Alkaline phosphatase=ALP(LLN=115; ULN=359) (U/L); alanine aminotransferase=ALT (LLN=8; ULN=42)(U/L); aspartate aminotransferase=AST (LLN=13; ULN=33) (U/L); albumin (LLN=3.7; ULN=5.2)(g/dL); bilirubin (LLN=0.3; ULN=1.2)(mg/dL); calcium (LLN=8.7; ULN=10.3)(mg/dL); creatinine (LLN=0.6; ULN=1.1)(mg/dL); potassium (LLN=3.6; ULN=4.9) (mEq/L); sodium (LLN=138; ULN=146) (mEq/L) (NCT00683904)
Timeframe: At screening and Days 8 and 15 of Cycle 1 (21 days)

,
InterventionParticipants (Number)
ALT: Grade 1 ( >1.0-2.5*ULN)ALT: Grade 2 (>2.5-5.0*ULN)ALT: Grade 3 ( >5.0-20.0*ULN )Albumin: Grade 1 (ALP: Grade 1 ( >1.0-2.5*ULN)AST: Grade 1 ( >1.0-2.5*ULN)AST: Grade 2 (>2.5-5.0*ULN)Bilirubin: Grade 1 (>1.0-1.5*ULN)Bilirubin: Grade 2 (>1.5-3.0*ULN)Calcium: Grade 1 (8.0-ULN -11.5)Creatinine: Grade 1 (>1.0-1.5*ULN)Potassium: Grade 1 (3.0-ULN-5.5)Sodium: Grade 1 (130-ULN-150)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL3204041115034
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL2114431104215

[back to top]

Number of Participants With Abnormalities in Hematology Laboratory Values by Worst CTC Grade

"LLN=lower level of normal; ULN=upper level of normal. Hemoglobin (g/dL; LLN=11.3; ULN=14.9); leukocytes (*10^3 c/uL; LLN=4.1; ULN=6.1); lymphocytes (*10^3 c/uL); neutrophils (absolute), neutrophils + bands (*10^3 c/uL); platelet count (*10^9 c/L; LLN=131; ULN=365)~Appendix 7.1.2" (NCT00683904)
Timeframe: At screening and Days 8 and 15 of Cycle 1 (21 days)

,
InterventionParticipants (Number)
Hemoglobin: Grade 1 (10.0- LLN)Hemoglobin: Grade 2 (8.0-<10.0)Hemoglobin: Grade 3 (6.5-<8.0)Hemoglobin: Grade 4 (<6.5)Hemoglobin: Not reportedLeukocytes: Grade 1 (3.0-Leukocytes: Grade 2 (2.0-<3.0)Leukocytes: Grade 3 (1.0-<2.0)Leukocytes: Grade 4 (<1.0)Leukocytes: Not reportedLymphocytes (absolute): Grade 1 (0.8-<1.5)Lymphocytes (absolute): Grade 2 (0.5-<0.8)Lymphocytes (absolute): Grade 3 (0.2-<0.5)Lymphocytes (absolute): Grade 4 (<0.2)Lymphocytes: Not reportedNeutrophils (absolute): Grade 1 (1.5-<2.0)Neutrophils (absolute): Grade 2 (1.0-<1.5)Neutrophils (absolute): Grade 3 (0.5-<1.0)Neutrophils (absolute): Grade 4 (<0.5)Neutrophils (absolute): Not reportedNeutrophils+bands (absolute): Grade 1 (1.5-<2.0)Neutrophils+bands (absolute): Grade 2 (1.0-<1.5)Neutrophils+bands (absolute): Grade 3 (0.5-<1.0)Neutrophils+bands (absolute): Grade 4 (<0.5)Neutrophils+bands (absolute): Not reportedPlatelet count: Grade 1 (75.0-Platelet count: Grade 2 (50.0-<75.0)Platelet count: Grade 3 (25.0-<50.0)Platelet count: Grade 4 (<25.0)Platelet count: Not reported
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL024000240040200011400123013200
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL051000150015000100501014032100

[back to top]

Volume of Distribution at Steady State of Ixabepilone

(NCT00683904)
Timeframe: Days 1 to 8 of Cycle 1 (21 days)

InterventionLiters (Mean)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL1131.02
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL1122.82

[back to top]

Total Body Clearance of Ixabepilone

(NCT00683904)
Timeframe: Days 1 to 8 of Cycle 1 (21 days)

InterventionLiters/hour (Mean)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL33.64
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL25.20

[back to top]

Time of Maximum Observed Plasma Concentration of Ixabepilone

(NCT00683904)
Timeframe: Days 1 to 8 of Cycle 1 (21 days)

InterventionHours (Mean)
Ixabepilone, 32 mg/m^2 + Carboplatin, 5 mg/Min/mL2.61
Ixabepilone, 32 mg/m^2 + Carboplatin, 6 mg/Min/mL2.43

[back to top]

Percentage of Participants With a Post Baseline Swallowing Diary Score >=4

Participants were provided with a swallowing diary to record issues with swallowing using a 5-point categorical scale: (1) no problems; (2) mild soreness; (3) swallowing solids with some difficulty; (4) inability to swallow solids; and (5) inability to swallow liquids. Participants rated swallowing over the previous 24 hours. The percentage of participants was calculated by dividing the number of with a post baseline swallowing diary score >=4 by total number of participants analyzed, multiplied by 100. No adjustments were made for the number of available assessments nor were any interpolation of missing assessments made. (NCT00686959)
Timeframe: Baseline through 30 Days Post Study

Interventionpercentage of participants (Number)
Arm A: Pemetrexed + Cisplatin and TRT33.8
Arm B: Etoposide + Cisplatin and TRT29.0

[back to top]

Overall Survival

Overall survival (OS) time is from baseline to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS time was censored at the last contact date the participant was known to be alive prior to the data cut-off date. OS was summarized using Kaplan-Meier estimates. (NCT00686959)
Timeframe: Baseline to Date of Death from Any Cause (Up to 71.4 Months)

Interventionmonths (Median)
Arm A: Pemetrexed + Cisplatin and TRT26.81
Arm B: Etoposide + Cisplatin and TRT24.97

[back to top]

Objective Response Rate (Complete Response [CR] + Partial Response [PR])

Overall response rate (ORR) is the best response of CR or PR as classified by the investigators according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1) guidelines. CR is defined as the disappearance of all target and non-target lesions, normalization of tumor marker level of non-target lesions, and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR is an at least 30% decrease in the sum of the diameters of target lesions (taking as reference the baseline sum diameter) without progression of non-target lesions or appearance of new lesions. Overall response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with at least 1 measurable lesion, multiplied by 100. (NCT00686959)
Timeframe: Baseline to Measured Progressive Disease (Up to 7 Months)

Interventionpercentage of participants (Number)
Arm A: Pemetrexed + Cisplatin and TRT35.9
Arm B: Etoposide + Cisplatin and TRT33.0

[back to top]

Progression-free Survival (PFS)

Progression-free survival (PFS) time is from baseline to the first date of documented objective progressive disease (PD) or death from any cause. For participants who were not known to have died or to have had objective PD as of the data inclusion cut-off date for a particular analysis, PFS was censored at the date of the last objective progression-free disease assessments. For participants who took any subsequent systemic anticancer therapy prior to progression or death, PFS was censored at the date of the last objective progression-free disease assessment prior to the start date of any subsequent systemic anticancer therapy. PFS time was summarized using Kaplan-Meier estimates. (NCT00686959)
Timeframe: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 66.6 Months)

Interventionmonths (Median)
Arm A: Pemetrexed + Cisplatin and TRT11.37
Arm B: Etoposide + Cisplatin and TRT9.76

[back to top]

Adverse Events: The Number of Deaths Per Treatment Group

The number of deaths that occurred while on study drug, the number of deaths due to adverse events (AEs) while on study drug, and the number of deaths due to the study disease (that is, disease progression) while on study drug are presented. In addition, the number of deaths within 30 days of treatment discontinuation, the number of deaths due to AEs within 30 days of treatment discontinuation, and the number of deaths due to study disease within 30 days of treatment discontinuation are presented. For both the deaths due to AEs that occurred on study and for deaths due to AEs that occurred within 30 days of treatment discontinuation, the causality (events assess as possibly related [poss related] to study drug per investigator judgement) is also presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module. (NCT00686959)
Timeframe: Baseline through 30 Days Post Study

,
Interventionparticipants (Number)
On study drug (total)On study drug: Due to AEOn study drug: Due to AE poss relatedOn study drug: Due to study diseaseWithin 30 Days of Discontinuation (disc) (total)Within 30 Days of Disc: Due to AEWithin 30 Days of Disc: Due to AE poss relatedWithin 30 Days of Disc: Due to study disease
Arm A: Pemetrexed + Cisplatin and TRT12105210525
Arm B: Etoposide + Cisplatin and TRT64306402

[back to top]

Survival Rates at 1, 2, and 3 Years

The probability that survival time is at least 1, 2, or 3 years was summarized using Kaplan-Meier estimates. (NCT00686959)
Timeframe: Baseline to Date of Death from Any Cause (Up to 71.4 Months)

,
Interventionprobability of survival (Number)
1 year (12 months)2 years (24 months)3 years (36 months)
Arm A: Pemetrexed + Cisplatin and TRT0.760.520.40
Arm B: Etoposide + Cisplatin and TRT0.770.520.37

[back to top]

First Site of Disease Failure in Terms of Relapse

The percentage of participants with first sites of disease failure in terms of relapse within the radiation treatment field, inside the thorax, (outside of the radiation field), or distant disease are presented. Results were summarized using Kaplan-Meier estimates. Some participants relapsed in more than 1 location/site and appear in more than a single category. (NCT00686959)
Timeframe: Baseline to Relapse (Up to 66.6 Months)

,
Interventionpercentage of participants (Number)
Relapsed within the radiation treatment fieldRelapsed inside thorax, outside of radiation fieldRelapsed distant disease
Arm A: Pemetrexed + Cisplatin and TRT37.320.550.0
Arm B: Etoposide + Cisplatin and TRT45.816.345.8

[back to top]

Objective Response Rate

Best overall response (complete or partial response), assessed using RECIST criteria (version 1.0) (NCT00687297)
Timeframe: Assessed every 2 cycles (1 cycle = 3 weeks during induction and 4 weeks during maintenance))

Interventionpercentage of participants (Number)
Randomized to Vandetanib Maintenance18.8
Randomized to Placebo Maintenance18.3

[back to top]

Progression-free Survival

Time from randomization to first evidence of disease progression or death. Patients alive without progression are censored at the date of last disease evaluation. (NCT00687297)
Timeframe: every 2 cycles (every 6 weeks during induction, every 8 weeks during maintenance)

Interventionmonths (Median)
Randomized to Vandetanib Maintenance4.5
Randomized to Placebo Maintenance4.2

[back to top]

Progression-free Survival

Time from randomization (prior to induction) to first evidence of disease progression or death without progression. Participants alive without progression were censored at the date of last disease evaluation. (NCT00687297)
Timeframe: Assessed every 2 cycles (1 cycle = 3 weeks during induction and 4 weeks during maintenance))

InterventionMonths (Median)
All Randomized Patients4.5

[back to top]

Time to Progression

Time To Progression (TTP) was defined as the interval between the start date of treatment and the date of occurrence of progressive disease (NCT00695292)
Timeframe: 18 months

Interventionmonths (Median)
Irinotecan, Carboplatin, Sunitinib7.6

[back to top]

Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment

Objective benefit is defined as substantial (30% or greater) shrinkage in tumor volume per RECIST 1.0. (NCT00695292)
Timeframe: 18 months

Interventionpercentage of participants (Number)
Irinotecan, Carboplatin, Sunitinib59

[back to top] [back to top]

Median Overall Survival

Overall survival was defined as the interval between the date of study entry until the date of death. (NCT00695292)
Timeframe: 18 months

Interventionmonths (Median)
Irinotecan, Carboplatin, SunitinibNA

[back to top]

One-year Survival, The Percentage of Patients Who Are Alive One Year After Completing Protocol Treatment

(NCT00695292)
Timeframe: 18 months

Interventionpercentage of participants (Number)
Irinotecan, Carboplatin, Sunitinib54

[back to top]

The Primary Efficacy End Point is the Number of Patients With an Objective Response.

Objective Response Rate to Treatment is defined as the Proportion of Patients With a Complete Response (CR) or Partial Response (PR). A Complete Response (CR) is the disappearance of all target lesions and a Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD (NCT00698451)
Timeframe: Approximately 280 days (from start of treatment to the end of 10 cycles of treatment where each cycle is 28 days)

InterventionParticipants (Number)
DOXIL/CARBOPLATIN/BEVACIZUMAB39

[back to top]

The Secondary Efficacy Endpoints is Duration of Objective Response.

Objective Response Rate to Treatment Defined as the Proportion of Patients With a Complete Response (CR) or Partial Response (PR) Where a Complete response (CR) is the disappearance of all target lesions and a Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Duration of response: Duration of response was defined only for subjects with CR or PR as the best overall response. It was calculated from the date of first documentation of response to the date of disease progression or death due to progressive disease. (NCT00698451)
Timeframe: Duration of response was defined only for subjects with CR or PR as the best overall response. It was calculated from the date of first documentation of response to the date of disease progression or death due to progressive disease.

InterventionDays (Median)
DOXIL/CARBOPLATIN/BEVACIZUMAB362

[back to top]

Percentage of Participants With Measurable Disease at Baseline Who Achieved CR, PR, or Stable Disease (SD) for at Least 6 Weeks

Percentage of participants with measurable disease at baseline who on assessment achieved CR, PR, or SD according to RECIST. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since start of treatment. Complete and partial responses must have been confirmed no less than 4 weeks after the criteria for response were first met. For participants with SD, follow-up assessments must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks. (NCT00700180)
Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression

Interventionpercentage of participants (Number)
Bevacizumab 7.5 mg Plus Chemotherapy76.8
Bevacizumab 15 mg Plus Chemotherapy78.6

[back to top]

Overall Survival - Time to Event

Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method. (NCT00700180)
Timeframe: Baseline, weekly to death due to any cause, or to end of study

Interventionmonths (Median)
Bevacizumab 7.5 mg Plus Chemotherapy13.4
Bevacizumab 15 mg Plus Chemotherapy13.7

[back to top]

Duration of Response - Time to Event

The median time, in months, from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR). Median Duration of Response was estimated using the Kaplan-Meier method. (NCT00700180)
Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.

Interventionmonths (Median)
Bevacizumab 7.5 mg Plus Chemotherapy5.8
Bevacizumab 15 mg Plus Chemotherapy5.6

[back to top]

Duration of Response - Percentage of Participants With an Event

Duration of response is defined as time in months from the first documentation of objective tumor response (CR or PR) to objective tumor progression or death due to any cause. Participants without an event (documented progression or death) were censored at the date of last follow-up for progression. Duration of response was only calculated for participants who had a confirmed objective tumor response (CR or PR). (NCT00700180)
Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression

Interventionpercentage of participants (Number)
Bevacizumab 7.5 mg Plus Chemotherapy80.4
Bevacizumab 15 mg Plus Chemotherapy78.5

[back to top]

Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by Dichotomized Baseline Plasma Marker Level

Overall response was analyzed and correlated within dichotomized (low- and high-level) baseline plasma biomarker (basic fibroblast growth factor [bFGF], E-selection, intracellular adhesion molecule [ICAM], placental growth factor [PlGF], vascular endothelial growth factor A [VEGF A], vascular endothelial growth factor receptor [VEGFR]-1, and VEGFR-2) subgroups: low-level equals (=) less than or equal to (≤) median baseline level, high-level=greater than (>) median baseline level. Per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.0 CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR defined as greater than or equal to (≥)30 percent (%) decrease under baseline of the sum of the longest diameter (LD) of all target lesions. No unequivocal progression of non-target disease; no new lesions. Complete and partial responses must have been confirmed no less than 4 weeks after criteria for response were first met (NCT00700180)
Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6 (Bv + chemo), Day 21 of Cycles 7, 8, 9, and 10 (Bv), Day 21 of every other cycle (Bv), and at disease progression.

,
Interventionpercentage of participants (Number)
bFGF low level (n=77,65)bFGF high level (n=66,75)E-selectin low level (n=73,69)E-selectin high level (n=70,71)ICAM low level (n=70,72)ICAM high level (n=29,32PlGF low level (n=82, 64)PlGF high level (n=27,29)VEGF A low level (n=73,67)VEGF A high level (n=67,73)VEGFR-1 low level (n=72,70)VEGFR-1 high level (n=71,70)VEGFR-2 low level (n=74,69)VEGFR-2 high level (n=69,71)
Bevacizumab 15 mg Plus Chemotherapy47.6949.3342.0354.9350.0047.0651.5651.7244.7853.4260.0037.1446.3850.70
Bevacizumab 7.5 mg Plus Chemotherapy42.8634.8536.9941.4338.5739.7337.8033.3342.4735.8237.5040.8532.4346.38

[back to top]

Overall Survival - Percentage of Participants With an Event

Overall survival was defined as the time between randomization and death due to any cause. Participants without an event were censored at the last time they were known to be alive. Overall Survival was estimated using the Kaplan-Meier method. (NCT00700180)
Timeframe: Baseline, weekly to 28 days after last dose of study treatment, every 8 weeks thereafter to death due to any cause

Interventionpercentage of participants (Number)
Bevacizumab 7.5 mg Plus Chemotherapy64.3
Bevacizumab 15 mg Plus Chemotherapy76.5

[back to top]

Progression-Free Survival - Time to Event

PFS was defined as the time between randomization and disease progression or death due to any cause. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization. Disease progression was evaluated according to the RECIST using CT scans, MRI scans, X-ray, bone scans, or clinical examination. Median PFS was estimated using the Kaplan-Meier method. (NCT00700180)
Timeframe: Baseline, Day 1, weekly to disease progression

Interventionmonths (Median)
Bevacizumab 7.5 mg Plus Chemotherapy6.8
Bevacizumab 15 mg Plus Chemotherapy6.7

[back to top]

Progression-Free Survival - Percentage of Participants With an Event

PFS was defined as the time between randomization and progressive disease (PD) according to RECIST criteria, or death due to any cause. PD was defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started. Disease progression was evaluated according to the RECIST using computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, X-ray, bone scans, or clinical examination. Participants without an event were censored at the date of last follow up for progression. Participants with no post baseline follow-up for progression were censored at the day of randomization. (NCT00700180)
Timeframe: Baseline, Day 1, weekly to disease progression

Interventionpercentage of participants (Number)
Bevacizumab 7.5 mg Plus Chemotherapy83.1
Bevacizumab 15 mg Plus Chemotherapy85.9

[back to top]

Percentage of Participants With Objective Response

Percentage of participants with CR or PR according to RECIST criteria. Per RECIST v1.0: CR defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was defined as ≥30% decrease under baseline of the sum of the LD of all target lesions. No unequivocal progression of non-target disease. No new lesions. Complete and partial responses were confirmed no less than 4 weeks after the criteria for response were first met. (NCT00700180)
Timeframe: Baseline, Day 21 of Cycles 2, 4, and 6, Day 21 of Cycles 7, 8, 9, and 10, Day 21 of every other cycle, and at disease progression

Interventionpercentage of participants (Number)
Bevacizumab 7.5 mg Plus Chemotherapy37.1
Bevacizumab 15 mg Plus Chemotherapy46.4

[back to top]

Overall Survival at 1 Year

Overall survival from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation. (NCT00712582)
Timeframe: 1 year

InterventionPercent of patients (Number)
Consolidation A98.3
Consolidation B96.9
Consolidation C50.0

[back to top]

2-year PFS From the Start of Induction Therapy Conditional

2-year PFS from the start of induction therapy conditional on attaining either a negative FDG-PET or a negative biopsy at the interim evaluation. (NCT00712582)
Timeframe: 2 years

Interventionpercentage of patients (Number)
Consolidation A86.6
Consolidation B90.6
Consolidation C0.4

[back to top]

Number of Participants With Adverse Events

Measure of safety and tolerability according to CTCAE version 3.0 (NCT00723125)
Timeframe: 2 years

Interventionparticipants (Number)
Cohort 115
Cohort 221

[back to top]

Pathological Complete Response Rates at Surgery

(NCT00723125)
Timeframe: at surgery approximately 5 months after initial treatment

Interventionparticipants (Number)
Cohort 116
Cohort 22

[back to top]

Progression-free Survival in the Subgroup of Participants With βIII-tubulin Positive Tumors

Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on-study tumor assessment, progression-free survival was censored at the date of randomization. A tumor was considered to be beta III (βIII)-tubulin positive if 50% or more of the tumor cells had a βIII-tubulin immunohistochemistry staining intensity equal to or greater than that of the positive control. (NCT00723957)
Timeframe: Randomization to disease progression or death (maximum reached: 14.39 months )

InterventionMonths (Median)
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)4.27
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)4.27

[back to top]

Median Length of Survival in the Overall Population and in the Subgroups of Patients With βIII-tubulin Positive (β3T+) and βIII-tubulin Negative (β3T-)Tumors

Overall Survival was computed for all randomized participants and was defined as the time between randomization and death. Participants who did not die at the end of the study were censored at their last known alive date. (NCT00723957)
Timeframe: Randomization to death or last known alive date, up to 31.34 months

,
InterventionMonths (Median)
βIII-tubulin positive subgroup (n=53, 51)βIII-tubulin negative subgroup (n=45, 48)Overall population
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)10.6116.9213.04
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)11.379.4010.15

[back to top]

Time to Response

Time to Response is defined as the time from randomization date until the date of first response (Partial Response [PR] or Complete Response [CR]) (NCT00723957)
Timeframe: Randomization to date of first response (PR or CR)

,
InterventionWeeks (Median)
Beta III positive (n=9, 15)Beta III negative (n=12, 13)Overall population
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)12.19.512.1
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)6.67.06.6

[back to top]

Percentage of Participants With Best Response of Complete Response (CR) or Partial Response (PR)

Response evaluated per Response Evaluaton in Solid Tumor (V1.0) guidelines and assessed using magnetic resonance imaging. Percentage of best response=the total number of participants with the best overall response of CR or PR divided by the total number of randomized participants in that treatment arm. CR=disappearance of all target lesions; PR=at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. (NCT00723957)
Timeframe: At randomization and then every 6 weeks to date of CR, PR, or progression for 6 21-day cycles

,
InterventionPercentage of participants (Mean)
βIII-tubulin positive subgroup (n=53, n=51)βIII-tubulin negative subgroup (n=45, n=48)Overall population
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)17.026.721.4
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)29.427.128.3

[back to top]

Number of Participants With Hematology Laboratory Results of Grade 3 or 4

LLN=lower level of normal. Leukocytes (leukopenia) Grade 1: NCT00723957)
Timeframe: At screening and weekly during 21-day cycle

,
InterventionParticipants (Number)
Leukopenia, Grade 3 or 4Neutropenia, Grade 3 or 4Thrombocytopenia, Grade 3 or 4Anemia, Grade 3 or 4
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)31541415
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)155110

[back to top]

Progression-free Survival in the Overall Population

Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on study tumor assessment, progression-free survival was censored at the date of randomization. (NCT00723957)
Timeframe: Randomization to disease progression or death, assessed to 12.29 months

InterventionMonths (Median)
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)5.29
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)5.13

[back to top] [back to top]

Number of Participants With Grade 3 or 4 Abnormalities in Liver Function and Urine Laboratory Test Results

ULN=upper level of normal. Alkaline phosphatase (ALP) Gr 1:>ULN to 2.5*ULN, Gr 2: >2.5 to 5.0*ULN, Gr 3: >5.0 to 20.0*ULN, Gr 4: >20.0*ULN; Aspartate aminotransferase (AST) Gr 1: >ULN to 2.5*ULN, Gr 2: >2.5 to 5.0*ULN, Gr 3: >5.0 to 20.0*ULN, Gr 4: >20.0*ULN (NCT00723957)
Timeframe: At screening and within 72 hours of start of 21-day cycle (Cycle 2 and beyond)

,
InterventionParticipants (Number)
ALP, Grade 3ALP. Grade 4AST, Grade 3AST, Grade 4
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)1000
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)0010

[back to top]

Progression-free Survival in the Subgroup of Participants With βIII-tubulin Negative Tumors

Progression-free survival is defined as the period from date of randomization to date of disease progression or death. For participants who do not progress or die at the end of the study, progression-free survival was censored at the last tumor assessment date. For those who have no on study tumor assessment, progression-free survival was censored at the date of randomization. (NCT00723957)
Timeframe: Randomization to disease progression or death (maximum reached: 12.29 months)

InterventionMonths (Median)
Ixabepilone, 32 mg/m^2 + Carboplatin (AUC 6)5.78
Paclitaxel, 200 mg/m^2 + Carboplatin (AUC 6)5.32

[back to top]

Progression Free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT00729612)
Timeframe: Up to 5 years

Interventionmonths (Median)
Treatment (Nab-paclitaxel, Carboplatin)5.0

[back to top]

Incidence and Intensity of Adverse Events Graded According to NCI CTCAE v. 3.0

The incidence and intensity of adverse events graded according to NCI CTCAE v. 3.0 will be evaluated using descriptive statistics (NCT00729612)
Timeframe: Up to 5 years

Interventionpatients (Number)
AnemiaNeutropeniaThrombocytopeniaLeukopenia/lymphopeniaSensory neuropathyFatigue
Treatment (Nab-paclitaxel, Carboplatin)7127131914

[back to top]

Overall Response Rate Defined as Complete or Partial Response as Assessed by RECIST Version 1.0 Criteria.

Response rate is overall response rate (CR+PR) as defined by RECIST criteriaPer Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00729612)
Timeframe: Up to 5 years

Interventionpercentage of patients (Number)
Partial ResponseComplete Response
Treatment (Nab-paclitaxel, Carboplatin)38.10

[back to top]

Overall Survival

Will be analyzed using a Kaplan-Meier methods. (NCT00729612)
Timeframe: Up to 5 years

Interventionmonths (Median)
Treatment (Nab-paclitaxel, Carboplatin)9.7

[back to top]

Summary of Participants Reporting Adverse Events

Data presented are the number of participants who experienced ramucirumab related treatment-emergent adverse events (TEAE), treatment related serious adverse events (SAE), or any Grade 3 or higher TEAE; any TEAE leading to discontinuation of ramucirumab treatment, and any TEAE leading to dose modification ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Event section. (NCT00735696)
Timeframe: Baseline up to 32.5 months

Interventionparticipants (Number)
Any ramucirumab related TEAEAny ramucirumab related Serious TEAEAny ramucirumab related Grade >= 3 TEAEAny TEAE Leading to Discontinuation of ramucirumabTEAE Leading to Dose Modification of ramucirumabAny ramucirumab related TEAE with Outcome of Death
Ramucirumab + Paclitaxel + Carboplatin3481513240

[back to top]

Duration of Response

The duration of a complete response (CR) or partial response (PR) was defined as the time from first objective status assessment of CR or PR to the first time of progression, initiation of additional antitumor therapy is first reported, or death as a result of any cause. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. (NCT00735696)
Timeframe: First dose up to 32.5 months

Interventionmonths (Median)
Ramucirumab + Paclitaxel + Carboplatin5.54

[back to top]

Serum Anti-Ramucirumab Antibody Assessment

The number of participants who developed treatment emergent antibody responses to ramucirumab after baseline. (NCT00735696)
Timeframe: Week 15 (Cycle 5)

Interventionparticipants (Number)
Ramucirumab + Paclitaxel + Carboplatin1

[back to top]

Maximum Concentration of Ramucirumab (Cmax)

(NCT00735696)
Timeframe: Week 18 (Cycle 6), at 1-Hour Post End of Infusion

Interventionmicrograms/milliliter (mcg/mL) (Mean)
Ramucirumab + Paclitaxel + Carboplatin372

[back to top]

Overall Survival (OS)

Overall survival is defined as the time from the first dose of study medication to the date of death from any cause. Participants who were alive at the end of the follow-up period or lost to follow-up were censored on the last date the patient was known to be alive. (NCT00735696)
Timeframe: First dose to death due to any cause, up to 32.5 months

Interventionmonths (Median)
Ramucirumab + Paclitaxel + Carboplatin16.85

[back to top]

Overall Survival (OS) at 1 Year

Data presented are the percentage of participants surviving at least 12 months after first dose of study medication. (NCT00735696)
Timeframe: First dose to 1 year

Interventionpercentage of participants (Number)
Ramucirumab + Paclitaxel + Carboplatin74.6

[back to top]

Percentage of Participants Who Are Progression-free (PFS) at 6 Months

Data presented are the percentage of participants without disease progression or death at 6 months. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progressive disease was defined as having at least a 20% increase in sum of longest diameter of target lesions or the appearance of one or more new lesions and/or unequivocal progression of existing nontarget lesions. (NCT00735696)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Ramucirumab + Paclitaxel + Carboplatin59.0

[back to top]

Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate ([ORR])

Objective response is Complete Response (CR) + Partial Response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) guidelines. CR is a disappearance of all target and non-target lesions; PR is at least a 30% decrease in the sum of the longest diameter of target lesions without new lesions and progression of non-target lesions. Objective response rate is calculated as a total number of participants with CR or PR divided by the total number of participants with measurable disease, multiplied by 100. (NCT00735696)
Timeframe: First dose to measured progressive disease or death due to any cause up to 32.5 months

Interventionpercentage of participants (Number)
Ramucirumab + Paclitaxel + Carboplatin55.0

[back to top]

Progression-free Survival (PFS)

"Defined as the time from date of first dose of study medication to the first documented disease progression as defined by Response Evaluation Criteria In Solid Tumors (RECIST 1.0), initiation of additional antitumor therapy was first reported or death due to any cause.~Participants who did not progress, who discontinued treatment for toxicity or a reason other than documented progression, or who were lost to follow-up before documented progression or death were censored at date of last tumor assessment. Participants who started new therapeutic anticancer treatment prior to documented progression or death were censored at date of last tumor assessment prior to new therapeutic anticancer therapy." (NCT00735696)
Timeframe: First dose to measured progressive disease or death due to any cause, up to 32.5 months

Interventionmonths (Median)
Ramucirumab + Paclitaxel + Carboplatin7.85

[back to top]

Number of Patients With Buccal Cells Demonstrating a Decline in Cyclin D1

Cyclin D1 levels were evaluated by immunoblot analyses of pretreatment (day 0) and paired posttreatment (day 4, 8 and 22) buccal swabs. (NCT00735878)
Timeframe: pretreatment (Day 0) and patient paired post- treatment (Days 4,8, 22) buccal swabs.

Interventionparticipants (Number)
Decline in Cyclin D1 expression on Day 4Decline in Cyclin D1 expression on Day 8Decline in Cyclin D1 expression on Day 22
Phase II/Group 2034

[back to top]

Objective Response Rate of Participants Using A Combination of ABT-751 and Carboplatin

The effectiveness of the combination with ABT-751 and carboplatin in patients with advanced NSCLC as measured by objective response rate. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) for target lesions and assessed by CT or MRI: Complete Response (CR), The disappearance of all known disease determined by two observations not less than four weeks apart.; Partial Response (PR), At least a 30% or more decrease in total tumor load of the lesions that have been measured to determine the effect of therapy by two observations not less than four weeks apart.; Overall Response (OR) = CR + PR (NCT00735878)
Timeframe: 42 days (end of cycle 2)

InterventionParticipants (Count of Participants)
Group 1/ Dose Escalating ABT-751 in Combination With Carboplat13

[back to top]

Maximum Tolerated Dose (MTD) of ABT-751 in Combination With Carboplatin

The maximum tolerated dose (MTD) of escalating ABT-751 in combination with fixed dose Carboplatin AUC 6 in patients with advanced non small cell lung cancer (NSCLC). Initially, 1 patient will be enrolled in dose level 1. If the patient experiences a Gr 2 toxicity, additional 2 patients will be enrolled at the dose level. If 1 of the 3 patients experience a Gr 3 toxicity or higher the cohort will be expanded to 6 patients. However, if 1 patient completes one cycle at the assigned dose regimen without a Gr 2 toxicity, enrollment in the next cohort (dose level 2) can begin. The rapid dose escalation scheme will apply to cohorts 1 through 3. (NCT00735878)
Timeframe: 21 Days (end of cycle 1)

Interventionmg of ABT-751 (Number)
Group 1/ Dose Escalating ABT-751 in Combination With Carboplat125

[back to top]

The Median Survival in the Study Population

Median overall survival using the Kaplan Meier method (NCT00735878)
Timeframe: from the start of the study until the last subject dies (up to 100 weeks)

Interventionmonths (Median)
All Participants Treated at MTD11.7

[back to top]

Number of Participants With a Tissue of Origin Successfully Predicted by the Assay

To evaluate the utility of the assay in identifying the tissue of origin in patients with carcinoma of unknown primary site (CUP), an archived tumor specimen was assayed upon study entry. If a tissue of origin was predicted by the assay, participants received standard site-specific therapy for that tumor type. When tissue of origin was not predicted by the assay, patients received standard empiric chemotherapy for CUP and were not followed further. If the assay was not completed due to inadequate amount of tumor in the biopsy specimen, patients were not treated on the study. (NCT00737243)
Timeframe: at baseline

Interventionparticipants (Number)
Biliary tract (gallbladder, bile duct)UrotheliumColorectumNon-small cell lungPancreasBreastOvaryGastroesophagealKidneyLiverSarcomaCervixNeuroendocrineProstateGerm cellSkin, squamousCarcinoid, intestineMesotheliomaThyroidEndometriumMelanomaSkin, basal-cellLung, small-cellLymphomaHead and NeckAdrenalunclassifiable
Patients With Successful Tumor Assays Performed52312827121211109866544433222211115

[back to top]

Overall Survival

Defined as the elapsed time from the start of treatment to the date of death from any cause or lost to follow-up. Participants lost to follow up were censored as of the last date known to be alive. (NCT00737243)
Timeframe: every 6-8 weeks (2 cycles) until death from any cause or lost to follow up, projected 18 months

Interventionmonths (Median)
More Treatment Responsive13.43
Less Treatment Responsive7.62

[back to top]

Progression Free Survival, the Length of Time, That Patients Were Alive From Their First Date of Treatment Until Worsening of Their Disease

(NCT00741988)
Timeframe: 18 months

Interventionmonths (Median)
Ixabepilone/Carboplatin5.3
Ixabepilone/Carboplatin/Bevacizumab6.7

[back to top] [back to top]

Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death

(NCT00741988)
Timeframe: 18 months

Interventionmonths (Median)
Ixabepilone/Carboplatin9.3
Ixabepilone/Carboplatin/Bevacizumab13.2

[back to top]

Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment

The Percentage of Patients Who Experience an Objective Benefit From Treatment (NCT00741988)
Timeframe: 18 months

Interventionpercentage of participants (Number)
Ixabepilone/Carboplatin29
Ixabepilone/Carboplatin/Bevacizumab50

[back to top]

Translational Research: Overall Survival (OS) Based on Cytoplasmic and Nuclear Thymidylate Synthase (TS) Expression

Cytoplasmic and nuclear Thymidylate Synthase (TS) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic and nuclear staining, and H score was calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). TS Positive have an H score >0 and TS Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive. (NCT00762034)
Timeframe: Baseline to date of death from any cause (up to 37.06 months)

,
Interventionmonths (Median)
TS Cytoplasm Positive (H score > 0; n=90, 83)TS Cytoplasm Negative (H score = 0; n=10, 6)TS Nucleus Positive (H score > 0; n=68, 51)TS Nucleus Negative (H score = 0; n=32, 38)
Pac/Carbo/Bev12.411.612.412.4
Pem/Carbo/Bev12.918.212.719.2

[back to top]

Translational Research: Overall Survival (OS) Based on Cytoplasmic and Membrane Folate Receptor Alpha (FR-α) Expression

Cytoplasmic and membrane Folate Receptor Alpha (FR-α) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system for cytoplasmic or membrane staining, and H score is a calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). FR-α Positive have an H score >0 and FR-α Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive. (NCT00762034)
Timeframe: Baseline to date of death from any cause (up to 37.06 months)

,
Interventionmonths (Median)
FR-α Cytoplasm Positive (H score > 0; n=64, 53)FR-α Cytoplasm Negative (H score = 0; n=34, 29)FR-α Membrane Positive (H score > 0; n=39, 22)FR-α Membrane Negative (H score = 0; n=59, 60)
Pac/Carbo/Bev14.311.215.511.3
Pem/Carbo/Bev14.412.019.212.9

[back to top]

Translational Research: Number of Participants With Epidermal Growth Factor Receptor (EGFR) Mutations

Epidermal Growth Factor Receptor (EGFR) mutations were measured by polymerase chain reaction (PCR). (NCT00762034)
Timeframe: Baseline

Interventionparticipants (Number)
EGFR mutation positiveEGFR mutation negative
Pem or Pac Plus Carbo/Bev11121

[back to top]

Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) Bevacizumab

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)

Interventionmicrogram*day per milliliter (μg•day/mL) (Geometric Mean)
Pem/Carbo/Bev3070
Pac/Carbo/Bev3160

[back to top]

Percentage of Participants With a Complete Response (CR) and Partial Response (PR) (Overall Response Rate)

Overall Response Rate (ORR) is the number of participants with a Complete Response (CR) and Partial Response (PR) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared to baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions. (NCT00762034)
Timeframe: Baseline to measured progressive disease (up to 37.06 months)

Interventionpercentage of participants (Number)
Pem/Carbo/Bev34.1
Pac/Carbo/Bev33.0

[back to top]

Overall Survival

Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive. (NCT00762034)
Timeframe: Baseline to date of death from any cause (up to 37.06 months)

Interventionmonths (Median)
Pem/Carbo/Bev12.55
Pac/Carbo/Bev13.40

[back to top]

Number of Participants Who Received a Transfusion

(NCT00762034)
Timeframe: Baseline to study endpoint (up to 37.06 months)

Interventionparticipants (Number)
Pem/Carbo/Bev116
Pac/Carbo/Bev44

[back to top]

Number of Participants Receiving Concomitant Medication

(NCT00762034)
Timeframe: Baseline to study endpoint (up to 37.06 months)

Interventionparticipants (Number)
Pem/Carbo/Bev406
Pac/Carbo/Bev421

[back to top]

Percentage of Participants With a Complete Response (CR), Partial Response (PR), and Stable Disease (SD) (Disease Control Rate)

Disease Control Rate (DCR) is the number of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD) divided by the total number of randomized participants per arm, then multiplied by 100. Response is based on the Response Evaluation Criteria In Solid Tumors (RECIST 1.0) criteria. Complete Response (CR) was defined as the disappearance of all target lesions. Partial Response (PR) was defined as at least a 30% decrease in sum of longest diameter of target lesions compared with baseline or the complete disappearance of target lesions, with persistence of 1 or more nontarget lesion(s) and no new lesions. Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions compared with the smallest sum of the longest diameter recorded since the start of treatment or the appearance of 1 or more new lesion(s). Stable Disease (SD) was defined as small changes that did not meet above criteria. (NCT00762034)
Timeframe: Baseline to measured progressive disease (up to 37.06 months)

Interventionpercentage of participants (Number)
Pem/Carbo/Bev65.9
Pac/Carbo/Bev69.8

[back to top]

Pharmacokinetics (PK): Pemetrexed Clearance (CL)

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)

Interventionmilliliters per minute (mL/min) (Geometric Mean)
Pem/Carbo/Bev72.1

[back to top]

Pharmacokinetics (PK): Bevacizumab Clearance (CL)

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)

Interventionliters per day (L/day) (Geometric Mean)
Pem/Carbo/Bev0.341
Pac/Carbo/Bev0.376

[back to top]

Safety and Toxicity Profile of Study Treatments

Safety and toxicity profile was defined as serious and other non-serious adverse events. A summary of serious and all other non-serious adverse events is located in the Reported Adverse Event module. (NCT00762034)
Timeframe: Baseline to study endpoint (up to 37.06 months)

,,,
Interventionparticipants (Number)
Serious Adverse Events (SAEs)Other Adverse Events (AEs)
Pac/Carbo/Bev; Induction Phase123431
Pac/Carbo/Bev; Maintenance Phase68296
Pem/Carbo/Bev; Induction Phase111432
Pem/Carbo/Bev; Maintenance Phase83288

[back to top]

Pharmacokinetics (PK): Platinum Clearance (CL) for Total (Bound and Unbound) and Unbound Forms

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form. (NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)

,
Interventionliters per hour (L/hr) (Geometric Mean)
Total (Bound and Unbound)Unbound (n=17, 13)
Pac/Carbo/Bev1.875.36
Pem/Carbo/Bev2.025.81

[back to top]

Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Pemetrexed

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)

Interventionmicrogram*hour per milliliter (μg•hr/mL) (Geometric Mean)
Pem/Carbo/Bev203

[back to top]

Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group- Neurotoxicity (FACT/GOG-Ntx)

"FACT/GOG-Ntx is a validated instrument used to measure quality of life (QOL) in participants with cancer and neurotoxicity (Ntx) consisting of 27-item FACT-General (G) and 11-item Ntx subscale. FACT-G is organized into domain subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items; each uses a 5 point rating scale (0=not at all and 4=equals very much). FACT/GOG-Ntx Total Score=sum 5 subscales and ranges from 0-152. Ntx Trial Outcome Index (TOI-Ntx)=PWB+FWB+NTX and range from 0-100. For all FACT scales, higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction." (NCT00762034)
Timeframe: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)

,
Interventionunits on a scale (Least Squares Mean)
FACT/GOG-Ntx Total Score (n=393, 389)Ntx Trial Outcome Index (TOI-Ntx)(n=393, 390)
Pac/Carbo/Bev-5.48-7.60
Pem/Carbo/Bev-0.60-2.79

[back to top]

Pharmacokinetics (PK): Area Under the Concentration Time Curve From Zero to Infinity (AUC(0-∞)) for Total (Bound and Unbound) Platinum and Unbound Platinum

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form. (NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)

,
Interventionmicrogram*hour per milliliter (μg•hr/mL) (Geometric Mean)
Total (Bound and Unbound)Unbound (n=17, 13)
Pac/Carbo/Bev18262.9
Pem/Carbo/Bev16055.7

[back to top]

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Total (Bound and Unbound) Platinum and Unbound Platinum

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form. (NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)

,
Interventionmicrograms per milliliter (μg/mL) (Geometric Mean)
Total (Bound and Unbound)Unbound (n=18, 15)
Pac/Carbo/Bev17.817.1
Pem/Carbo/Bev18.421.1

[back to top]

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Bevacizumab

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)

Interventionmicrograms per milliliter (μg/mL) (Geometric Mean)
Pem/Carbo/Bev276
Pac/Carbo/Bev302

[back to top]

Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - General (FACT-G)

"The FACT-G is a validated instrument used to measure quality of life (QOL) in participants with cancer consisting of the 27-item questionnaire and is organized into subscales, each designed to assess a QOL domain: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0=not at all and 4=equals very much). FACT-G Total is the sum of the scores of all 4 subscales and ranges from 0 to 108. Higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction." (NCT00762034)
Timeframe: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)

Interventionunits on a scale (Least Squares Mean)
Pem/Carbo/Bev0.51
Pac/Carbo/Bev0.18

[back to top]

Pharmacokinetics (PK): Elimination Half-life (t1/2) for Bevacizumab

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.75, 1.5, 3, 5, 7, 24, 48, 72, 168, 336, and 503 hours post-dose)

Interventiondays (Geometric Mean)
Pem/Carbo/Bev14.8
Pac/Carbo/Bev12.8

[back to top]

Pharmacokinetics (PK): Elimination Half-life (t1/2) for Pemetrexed

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)

Interventionhours (hr) (Geometric Mean)
Pem/Carbo/Bev2.88

[back to top]

Pharmacokinetics (PK): Maximum Observed Drug Concentration (Cmax) for Pemetrexed

(NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.17, 0.33, 0.58, 0.83, 1, 1.75, 2.5, 4. 6. 8, and 24 hours post-dose)

Interventionmicrograms per milliliter (μg/mL) (Geometric Mean)
Pem/Carbo/Bev122

[back to top]

Duration of Hospitalizations Per Participant

Length of hospitalization in participants hospitalized during the study or within 30 days of discontinuation regardless of whether the hospitalization was or was not due to study drug. (NCT00762034)
Timeframe: Baseline to study endpoint (up to 37.06 months)

Interventiondays (Mean)
Pem/Carbo/Bev9.4
Pac/Carbo/Bev8.0

[back to top]

Time to Progressive Disease

Time to progressive disease was defined as the time from randomization to the first date of objective disease progression. Participants were censored at date of last PFS assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy, whichever was earlier. (NCT00762034)
Timeframe: Baseline to measured progressive disease (up to 37.06 months)

Interventionmonths (Median)
Pem/Carbo/Bev7.03
Pac/Carbo/Bev6.04

[back to top]

Translational Research: Overall Survival (OS) Based on Nuclear Thyroid Transcription Factor-1 (TTF-1) Expression Regardless of Study Treatment

Nuclear Thyroid Transcription Factor-1 (TTF-1) expression was measured using an Immunohistochemistry (IHC) assay which were scored using a 0 (negative, no staining) to 3+ (brightest staining) scoring system, and H score is a calculated using formula: 1x(percentage of cells stained 1+) + 2x(percentage of cells stained 2+) + 3x(percentage of cells stained 3+). TTF-1 Positive have an H score >0 and TTF-1 Negative have an H score=0. Overall survival (OS) is the duration from date of randomization to date of death from any cause. Participants were censored at the date they were last known to be alive. (NCT00762034)
Timeframe: Baseline to date of death from any cause (up to 37.06 months)

Interventionmonths (Median)
TTF-1 Positive (H Score > 0)14.9
TTF-1 Negative (H Score = 0)8.7

[back to top]

Change From Baseline in Participant Reported Outcomes as Assessed by the Functional Assessment of Cancer Therapy - Lung (FACT-L)

"FACT-L is a valid instrument used to measure quality of life (QOL) in participants with cancer consisting of the 27-item FACT-General (G) and 9-item lung cancer subscale (LCS). FACT-G is organized into subscales: physical well-being (PWB)-7 items; social/family well-being (SWB)-7 items; emotional well-being (EWB)-6 items; functional well-being (FWB)-7 items. Each item uses a 5 point rating scale (0=not at all and 4=equals very much). FACT-L Total Score=4 subscales + LCS and ranges from 0 to 144. Trial Outcome Index-Lung (TOI-L)=PWB+FWB+LCS and ranges from 0 to 92. Higher scores indicate better QOL. Least squares mean (LSmean) change is calculated using the linear-mixed model (LMM) analysis controlled for treatment, baseline value, time point and treatment by time point interaction." (NCT00762034)
Timeframe: Baseline, up to first 10 cycles (4 induction and 6 maintenance cycles, cycle=21 days)

,
Interventionunits on a scale (Least Squares Mean)
FACT-L Total Score (n=397, 392)Trial Outcome Index-Lung (TOI-L) (n=396, 394)
Pac/Carbo/Bev1.66-0.40
Pem/Carbo/Bev1.88-0.38

[back to top]

Progression Free Survival Time

Progression free survival (PFS) is defined as the time from date of randomization to the date of objective disease progression or death due to any cause. Participants were censored at date of last PFS assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy, whichever was earlier. (NCT00762034)
Timeframe: Baseline to measured progressive disease or date of death from any cause (up to 33.54 months)

Interventionmonths (Median)
Pem/Carbo/Bev6.04
Pac/Carbo/Bev5.55

[back to top]

Pharmacokinetics (PK): Elimination Half-life (t1/2) for Total (Bound and Unbound) Platinum and Unbound Platinum

Platinum is a metabolite of Carboplatin (Carbo) and is found in the blood as both a bound and unbound form. (NCT00762034)
Timeframe: Cycle 1 (pre-dose, 0.25, 0.5, 0.67, 1.42, 2.17, 4, 6, 8, 24, 48, and 72 hours post-dose)

,
Interventionhours (hr) (Geometric Mean)
Total (Bound and Unbound)Unbound (n=17, 13)
Pac/Carbo/Bev86.41.95
Pem/Carbo/Bev65.62.03

[back to top]

Progression-Free Survival (PFS)

"Tumor progression was assessed according to the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), presented below.~Complete Response (CR) = Disappearance of all target lesions~Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions~Objective Response (OR) = CR + PR~Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)~Stable disease (SD) = Small changes that do not meet any of the above criteria.~Progression-Free Survival is assessed as the number of evaluable participants who were alive without disease progression at 1 year. Participants without out assessment at 12 months will not be included." (NCT00780494)
Timeframe: 12 months

InterventionParticipants (Count of Participants)
Bevacizumab+ Carboplatin +Capecitabine9

[back to top]

Overall Survival (OS)

Overall survival (OS) will be assessed from time from the date of enrollment to the date of death due to any cause or the last date the patient was known to be alive (censored observation) at the date of data cutoff for the final analysis. The outcome is presented as the median survival in days with standard deviation. (NCT00780494)
Timeframe: 7.5 years

InterventionDays (Median)
Bevacizumab+ Carboplatin +Capecitabine458

[back to top] [back to top]

Objective (Overall) Therapeutic Response

"Tumor response was assessed per the Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions, and assessed by physical measurement; magnetic resonance imaging (MRI); computed tomography (CT), positron emission tomography (PET)-CT; and/or X-rays/radiologic scan. Response was determined based on the criteria below.~Complete Response (CR) = Disappearance of all target lesions~Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions~Objective Response (OR) = CR + PR~Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)~Stable disease (SD) = Small changes that do not meet any of the above criteria The outcome is provided as the number of participants who achieved each of the defined responses, with objective (overall) response defined as the sum of CR and PR. The outcome is reported as values without dispersion." (NCT00780494)
Timeframe: 12 months

InterventionParticipants (Count of Participants)
Partial ResponseComplete Response (CR)Objective Response (OR) = CR + PRStable DiseaseProgressive Disease
Bevacizumab+ Carboplatin +Capecitabine1801865

[back to top]

Maximum Administered Dose of Dasatinib (Phase I)

This field captured the maximum dose of dasatinib administered. (NCT00788125)
Timeframe: 28 days after start of course 1

Interventionmg/m2 dose BID (Number)
Period 1: 35 mg/m^2/Dose BID PO Dasatinib x 17 Days35

[back to top]

Overall Survival

Medians of survival time, and their confidence intervals. (NCT00795340)
Timeframe: at every 3 months visit throughout trial, a median of 13.1 months.

Interventionmonths (Median)
Cediranib12.2
Placebo12.1

[back to top]

Objective Tumor Response as Assessed by RECIST Criteria v1.1.

Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression. (NCT00795340)
Timeframe: Every 6 weeks at the end of every 2 cycles during protocol treatment and every 12 weeks after protocol treatment until progression.

Interventionpercentage of participants (Number)
Cediranib52
Placebo34

[back to top]

Progression-free Survival

Medians of PFS and their confidence intervals by arm (NCT00795340)
Timeframe: at every 3 months visit throughout trial, a median of 12 months

Interventionmonths (Median)
Cediranib5.52
Placebo5.45

[back to top]

Pharmacokinetic Parameter of Time of Maximum Observed Concentration (Tmax) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

Tmax reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.. (NCT00796991)
Timeframe: Day 1 (0 h) to Day 43

,,
Interventionh (Median)
Tmax of Ipilimumab N=14, 14, 12Tmax of Paclitaxel (Day 1) N=20, 0, 0Tmax of Paclitaxel (Day 43) N=14, 0, 0Tmax of Dacarbazine (Day 1) N=0, 18, 0Tmax of Dacarbazine (Day 43) N=0, 15, 0Tmax of AIC (Day 1) N=0, 19 0Tmax of AIC (Day 43) N=0, 16, 0
Dacarbazine, Ipilimumab4.00NANA1.001.001.001.00
Ipilimumab1.56NANANANANANA
Paclitaxel, Carboplatin, Ipilimumab1.513.003.00NANANANA

[back to top]

Pharmacokinetic Parameter Volume of Distribution at Steady State (Vss) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

Vss reported in liters(L): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. (NCT00796991)
Timeframe: Day 1 (0 h) to Day 43

,,
InterventionL (Geometric Mean)
Vss of Ipilimumab N=14, 14, 12Vss of Paclitaxel (Day 43) N=14, 0, 0Vss of Dacarbazine (Day 43) N=0, 16, 0Vss of AIC (Day 1) N=0, 17, 0
Dacarbazine, Ipilimumab4.88NA107.90342.64
Ipilimumab5.05NANANA
Paclitaxel, Carboplatin, Ipilimumab5.10205.63NANA

[back to top]

Area Under the Concentration Time Curve (AUC) From Time Zero to 21 Days [AUC(0-21d)] for Ipilimumab and AUC Time Zero Extrapolated to Infinity [AUC(INF)] for Paclitaxel, Dacarbazine and the Active Metabolite AIC - Pharmacokinetic Analysis Population

AUC=micrograms*hour(h) per mL (µg*h/mL): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. (NCT00796991)
Timeframe: Day 1 (0 h) to Day 43

,,
Interventionµg*h/mL (Geometric Mean)
AUC(0-21d) of Ipilimumab N=14, 14, 12AUC(INF) of Paclitaxel (Day 1) N=20, 0, 0AUC(INF) of Paclitaxel (Day 43) N=14, 0, 0AUC(INF) of Dacarbazine (Day 1) N=0, 19, 0AUC(INF) of Dacarbazine (Day 43) N=0, 16, 0AUC(INF) of AIC (Day 1) N=0, 18, 0AUC(INF) of AIC (Day 43) N=0, 16, 0
Dacarbazine, Ipilimumab49569.06NANA47.3641.1317.6817.38
Ipilimumab54039.79NANANANANANA
Paclitaxel, Carboplatin, Ipilimumab46925.3612.3713.41NANANANA

[back to top]

Mean Absolute Lymphocyte Count (ALC) at Each Nominal Ipilimumab Induction Dose and at End of the Induction Period - Pharmacodynamic Population

Absolute lymphocyte counts were obtained from routine hematology panels from 28 days prior to the first treatment with any study medication through the end of the Induction-Dosing Period and were reported as number*10^3 cells per micro liter (x10^3 c/µL). (NCT00796991)
Timeframe: Day to Week 12

,,
Intervention10^3 cells/µL (Mean)
Nominal Ipilimumab Induction Dose Number 1Nominal Ipilimumab Induction Dose Number 2Nominal Ipilimumab Induction Dose Number 3Nominal Ipilimumab Induction Dose Number 4End of Ipilimumab Induction dosing Period
Dacarbazine, Ipilimumab1.412.051.961.872.07
Ipilimumab1.281.561.991.801.73
Paclitaxel, Carboplatin, Ipilimumab1.191.621.431.421.67

[back to top]

Mean Baseline Change in Body Temperature at Weeks 16 and 48 - All Treated Population

Temperature was obtained while the participant was sitting down and was measured in degrees Fahrenheit (F). During the induction phase this vital sign was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Temperature was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventiondegrees F (Mean)
Temperature at Week 16 (N=1, 6, 9)Temperature at Week 48 (N=1, 4, 4)
Dacarbazine, Ipilimumab-0.10.0
Ipilimumab0.2-0.2
Paclitaxel, Carboplatin, Ipilimumab-0.50.4

[back to top]

Mean Change From Baseline at Weeks 16 and 48 in Diastolic and Systolic Blood Pressure - All Treated Population

Blood pressure was obtained while the participant was sitting down and was measured in millimeters of mercury (mmHg). During the induction phase blood pressure was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Orthostatic blood pressure was to be measured when clinically indicated (for example, participant was experiencing lightheadedness, dizziness, syncope). Blood pressures were recorded at Weeks 1, 4, 7, 10,13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
InterventionmmHg (Mean)
Diastolic Blood Pressure at Week 16 (N=1, 6, 9)Diastolic Blood Pressure at Week 48 (N=1, 4, 4)Systolic Blood Pressure at Week 16 (N=1, 6, 9)Systolic Blood Pressure at Week 48 (N=1, 4, 4)
Dacarbazine, Ipilimumab6.67.02.71.0
Ipilimumab4.98.59.712.0
Paclitaxel, Carboplatin, Ipilimumab10.02.022.05.0

[back to top]

Mean Change From Baseline in Pulse Rate at Weeks 16 and 48 - All Treated Population

Pulse rate was obtained while the participant was sitting down and measured in beats per minute (bpm). During the induction phase pulse rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Pulse rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionbpm (Mean)
Pulse Rate at Week 16 (N=1, 6, 9)Pulse Rate at Week 48 (N=1, 4, 4)
Dacarbazine, Ipilimumab0.3-9.5
Ipilimumab-0.77.5
Paclitaxel, Carboplatin, Ipilimumab24.0-3.0

[back to top]

Mean Change From Baseline in Respiration Rate at Weeks 16 and 48 - All Treated Population

Respiration rate was obtained while the participant was sitting down and measured in breaths per minute (bpm). During the induction phase respiration rate was collected 30 minutes prior to dosing and every 30 minutes for the duration of the ipilimumab infusion. Respiration rate was recorded at Weeks 1, 4, 7, 10, 13, 16, 19, and 22 during the Induction Phase, and at Weeks 24, 36, and 48 during the Maintenance Phase. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionbpm (Mean)
Respiration Rate at Week 16 (N=1, 5, 6)Respiration Rate at Week 48 (N=1, 3, 3)
Dacarbazine, Ipilimumab1.4-2.7
Ipilimumab-0.8-1.3
Paclitaxel, Carboplatin, Ipilimumab0-2.0

[back to top]

Number of Participants in Best Overall Response Categories Based on Immune Related (ir) Response Criteria (RC) - All Treated Participants

Assessments: Weeks 12, 16, 20, and 24. Participants with resected index or new lesions considered progressed in their disease. The immune-related (ir) response criteria (irRC) represents further modifications of mWHO criteria reflecting clinical experience with ipilimumab in which objective and durable responses (as per mWHO) were observed in participants following progression and without intervening alternative anti-cancer therapy. Immune-related (ir)Complete Response (irCR): Complete disappearance of all index lesions; ir Partial Response (irPR): Decrease, relative to baseline, of 50% or greater in sum of products of the two largest perpendicular diameters of all index and all new measurable lesions, in the absence of irCR; ir Stable Disease (irSD): Does not meet criteria for irCR or irPR, in the absence of progressive disease (PD); ir PD: At least 25% increase in Tumor Burden compared to sum of product diameters (SPD) at nadir. ir Unknown=participants overall response not known. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
ir Complete Responseir Partial Responseir Stable Diseaseir Progressive Diseaseir Unknown
Dacarbazine, Ipilimumab15571
Ipilimumab05663
Paclitaxel, Carboplatin, Ipilimumab14573

[back to top]

Number of Participants in Best Overall Response Categories Based on Modified World Health Organization (mWHO) Criteria - All Treated Participants

Assessments for antitumor activity by physical exam and routine anatomic imaging were at Week 12 and confirmatory imaging at Weeks 16, 20, and 24. Participants with resected index or new lesions were considered progressed in their disease. Complete Response (CR): Complete disappearance of all index lesions; Partial Response (PR): Decrease, relative to baseline, of 50% or greater in the sum of the products of the two largest perpendicular diameters of all index lesions, in the absence of Complete Response; Stable Disease (SD): Does not meet criteria for complete or partial response, in the absence of progressive disease. Participants with PR or CR that was not confirmed after at least 4 weeks are scored as SD unless they have new primary lesions; Progressive Disease: At least 25% increase in the sum of products of all index lesions and/or the appearance of any new lesion(s). Unknown=the participants overall response was not known. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseUnknown
Dacarbazine, Ipilimumab14581
Ipilimumab05483
Paclitaxel, Carboplatin, Ipilimumab11693

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Hemoglobin - All Treated Population

Hemoglobin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 10.0 - less than (<) lower limit of normal (LLN); GRADE (2): 8.0 - < 10.0; GRADE (3): 6.5 - < 8.0; GRADE (4): < 6.5 (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Hemoglobin Grade 0Hemoglobin Grade 1Hemoglobin Grade 2Hemoglobin Grade 3Hemoglobin Not Reported
Dacarbazine, Ipilimumab413110
Ipilimumab510401
Paclitaxel, Carboplatin, Ipilimumab39800

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Leukocytes - All Treated Population

Leukocytes are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN; GRADE (2): 2.0 - < 3.0; GRADE (3): 1.0 - < 2.0; GRADE (4): < 1.0. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Leukocytes Grade 0Leukocytes Grade 1Leukocytes Grade 2Leukocytes Grade 3Leukocytes Grade 4Leukocytes Not Reported
Dacarbazine, Ipilimumab1342000
Ipilimumab1711001
Paclitaxel, Carboplatin, Ipilimumab842510

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst Common Terminology Criteria (CTC) Grade for Lymphocytes - All Treated Population

Lymphocytes (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) version (v) 3.0 was used to determine Grade. GRADE (1): 0.8 - < 1.5; GRADE (2): 0.5 - < 0.8; GRADE (3): 0.2 - < 0.5; GRADE (4): < 0.2 (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Lymphocytes Grade 0Lymphocytes Grade 1Lymphocytes Grade 2Lymphocytes Grade 3
Dacarbazine, Ipilimumab51310
Ipilimumab61130
Paclitaxel, Carboplatin, Ipilimumab41231

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alanine Aminotransferase (ALT) - All Treated Population

ALT was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
ALT Grade 0ALT Grade 1ALT Grade 2
Dacarbazine, Ipilimumab1810
Ipilimumab1631
Paclitaxel, Carboplatin, Ipilimumab1820

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Albumin - All Treated Population

Albumin was measured in grams per deciliter (g/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): < LLN - 3.0; GRADE (2): < 3.0 - 2.0; GRADE (3): < 2.0 g/dL. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Albumin Grade 0Albumin Grade 1
Dacarbazine, Ipilimumab145
Ipilimumab146
Paclitaxel, Carboplatin, Ipilimumab173

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Alkaline Phosphatase - All Treated Population

Alkaline Phosphatase was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Alkaline Phosphatase Grade 0Alkaline Phosphatase Grade 1Alkaline Phosphatase Grade 2
Dacarbazine, Ipilimumab1810
Ipilimumab1802
Paclitaxel, Carboplatin, Ipilimumab1460

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Aspartate Aminotransferase (AST) - All Treated Population

AST was measured as Units per Liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 2.5 * upper limits of normal (ULN); GRADE (2): > 2.5 - 5.0 * ULN; GRADE (3): > 5.0 - 20.0 * ULN; GRADE (4): > 20.0 * ULN. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
AST Grade 0AST Grade 1AST Grade 2
Dacarbazine, Ipilimumab1810
Ipilimumab1541
Paclitaxel, Carboplatin, Ipilimumab1820

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils - All Treated Population

Neutrophils (absolute) are measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5 (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Neutrophils Grade 0Neutrophils Grade 1Neutrophils Grade 3
Dacarbazine, Ipilimumab1801
Ipilimumab1910
Paclitaxel, Carboplatin, Ipilimumab2000

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Neutrophils Plus Bands - All Treated Population

Neutrophils plus bands (absolute) were measured as *10^3 cells per microliter (c/µL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 1.5 - < 2.0; GRADE (2): 1.0 - < 1.5; GRADE (3): 0.5 - < 1.0; GRADE (4): < 0.5. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Neutrophils Plus Bands Grade 0Neutrophils Plus Bands Grade 1Neutrophils Plus Bands Grade 3
Dacarbazine, Ipilimumab1801
Ipilimumab1910
Paclitaxel, Carboplatin, Ipilimumab2000

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Platelet Count - All Treated Population

Platelets were measured as *10^9 cells per liter (c/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 75.0 - < LLN; GRADE (2): 50.0 - < 75.0; GRADE (3): 25.0 - < 50.0; GRADE (4): < 25.0. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Platelet Count Grade 0Platelet Count Grade 1
Dacarbazine, Ipilimumab190
Ipilimumab182
Paclitaxel, Carboplatin, Ipilimumab200

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Serum Potassium (High) - All Treated Population

Serum potassium was measured as milliequivalents per liter (mEq/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 3.0 - < LLN OR > ULN - 5.5;; GRADE (2): > 5.5 - 6.0; GRADE (3): 2.5 - < 3.0 > 6.0 - 7.0; GRADE (4): < 2.5 mEq/L. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Serum Potassium (High) Grade 0Serum Potassium (High) Grade 1Serum Potassium (High) Grade 2
Dacarbazine, Ipilimumab1720
Ipilimumab1712
Paclitaxel, Carboplatin, Ipilimumab2000

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Amylase - All Treated Population

Amylase was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 * ULN. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Total Amylase Grade 0Total Amylase Grade 1Total Amylase Grade 2Total Amylase Grade 3
Dacarbazine, Ipilimumab19000
Ipilimumab16211
Paclitaxel, Carboplatin, Ipilimumab20000

[back to top]

Pharmacokinetic Parameter of Terminal Elimination Half Life (T-HALF) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

T(HALF) reported in hours (h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. (NCT00796991)
Timeframe: Day 1 (0 h) to Day 43

,,
Interventionh (Mean)
T(HALF) of Ipilimumab N=14, 14, 12T(HALF) of Paclitaxel (Day 1) N=20, 0, 0T(HALF) of Paclitaxel (Day 43) N=14, 0, 0T(HALF) of Dacarbazine (Day 1) N=0, 19, 0T(HALF) of Dacarbazine (Day 43) N=0, 16, 0T(HALF) of AIC (Day 1) N=0, 18, 0T(HALF) of AIC (Day 43) N=0, 16, 0
Dacarbazine, Ipilimumab13.39NANA2.112.072.242.21
Ipilimumab15.25NANANANANANA
Paclitaxel, Carboplatin, Ipilimumab13.9310.2610.41NANANANA

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Bilirubin - All Treated Population

Total Bilirubin was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * upper limits of normal (ULN); GRADE (2): > 1.5 - 3.0 * ULN; GRADE (3): > 3.0 - 10.0 * ULN; GRADE (4): > 10.0 * ULN. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Total Bilirubin Grade 0Total Bilirubin Grade 1Total Bilirubin Grade 2
Dacarbazine, Ipilimumab1711
Ipilimumab1820
Paclitaxel, Carboplatin, Ipilimumab2000

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Calcium (High) - All Treated Population

Total Calcium was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): 8.0 - < LLN OR > ULN - 11.5; GRADE (2): 7.0 - < 8.0 > 11.5 - 12.5; GRADE (3): 6.0 - < 7.0 > 12.5 - 13.5; GRADE (4): < 6.0 > 13.5 mg/dL. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Total Calcium (High) Grade 0Total Calcium (High) Grade 1
Dacarbazine, Ipilimumab190
Ipilimumab191
Paclitaxel, Carboplatin, Ipilimumab182

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Total Lipase - All Treated Population

Total Lipase (as measured with a turbidimetric assay) was measured as units per liter (U/L). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 - 1.5 * ULN; GRADE (2): > 1.5 - 2.0 * ULN; GRADE (3): > 2.0 - 5.0 * ULN; GRADE (4): > 5.0 X ULN. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Total Lipase Grade 0Total Lipase Grade 1Total Lipase Grade 4Total Lipase Not Reported
Dacarbazine, Ipilimumab60013
Ipilimumab40115
Paclitaxel, Carboplatin, Ipilimumab12107

[back to top]

Number of Participants on Treatment With Toxicity Changes From Baseline by Worst CTC Grade for Uric Acid - All Treated Population

Uric acid was measured as milligrams per deciliter (mg/dL). National Cancer Institute Common Terminology Criteria (CTC) v3.0 was used to determine Grade. GRADE (1): > 1.0 * ULN - 10.0; GRADE (4): > 10.0 mg/dL. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Uric Acid Grade 0Uric Acid Grade 1
Dacarbazine, Ipilimumab191
Ipilimumab173
Paclitaxel, Carboplatin, Ipilimumab200

[back to top]

Number of Participants With Adverse Events, Serious Adverse Events, Deaths, and Discontinuation Due to Adverse Events From Day 1 to Week 48 - All Treated Population

Adverse events (AEs) and Serious AEs (SAEs) were graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse events version 3.0. Week 48 database lock was 27 July 2010. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Participants with AEsParticipants with SAEsParticipants with SAEs Treatment-RelatedDeathsDeaths Treatment-RelatedParticipants discontinued due to AE(s)
Dacarbazine, Ipilimumab1986507
Ipilimumab2095705
Paclitaxel, Carboplatin, Ipilimumab20941206

[back to top]

Number of Participants With Objective Response to Treatment and Disease Control Using mWHO Criteria - All Randomized Participants

Number of participants with an objective response to treatment excluded participants with a best overall response (BOR) of Stable Disease (SD). Disease control is non-progression of disease while on treatment. A participant was considered to have achieved disease control if he/she had a BOR of CR, PR, or SD in the absence of resected index lesions or new lesions while the participant was considered to have an objective response to treatment in he/she had a BOR of CR or PR in the absence of resected index lesions or new lesions. (NCT00796991)
Timeframe: Day 1 to Week 48

,,
Interventionparticipants (Number)
Participants with Objective ResponseParticipants with Disease Control
Dacarbazine, Ipilimumab510
Ipilimumab59
Paclitaxel, Carboplatin, Ipilimumab28

[back to top]

Pharmacokinetic Parameter Maximum Observed Serum Concentration (Cmax) for Ipilimumab, Paclitaxel, Dacarbazine and the Active Metabolite for Dacarbazine, 5-aminoimidazole-4carboxamide (AIC)- Pharmacokinetic Analysis Population

Cmax=micrograms per milliliter (µg/mL): drug concentration versus time for ipilimumab (Day 43) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma by Enzyme-linked Immunosorbent Assay (ELISA); lower level of quantitation (LLOQ)=0.8 µg/mL; upper limit of quantitation (ULOQ)=25.6 µg/mL; Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; from Day 162 on every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined using liquid chromatography tandem mass spectrometry (LC/MS/MS) detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography atmospheric pressure ionization (API) tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose. (NCT00796991)
Timeframe: Day 1 (0 h) to Day 43

,,
Interventionµg/mL (Geometric Mean)
Cmax of Ipilimumab N=14, 14, 12Cmax of Paclitaxel (Day 1) N=20, 0, 0Cmax of Paclitaxel (Day 43) N=14, 0, 0Cmax of Dacarbazine (Day 1) N=0, 19, 0Cmax of Dacarbazine (Day 43) N=0, 16, 0Cmax of AIC (Day 1) N=0, 19, 0Cmax of AIC (Day 43) N=0, 17, 0
Dacarbazine, Ipilimumab246.50NANA18.2318.613.573.98
Ipilimumab251.05NANANANANANA
Paclitaxel, Carboplatin, Ipilimumab234.543.353.19NANANANA

[back to top]

Pharmacokinetic Parameter of Clearance (CLT) for Ipilimumab, Paclitaxel, Dacarbazine and Active Metabolite AIC - Pharmacokinetic Analysis Population

CLT reported in milliliters/hour (mL/h): derived from drug concentration versus time for ipilimumab (Day 43 only) and paclitaxel, dacarbazine, and AIC (Days 1, 43). Ipilimumab determined from plasma ELISA; LLOQ=0.8 µg/mL; ULOQ=25.6 µg/mL; sample times on Day 43=0 hour (h) predose, 1.5, 4.0, 24, 72, 168, 336, 504 h post dose; starting Day 162 every 12 weeks (Day 1 and 22= 0 h). Paclitaxel determined from plasma using LC/MS/MS detection; LLOQ=10 nanograms per milliliter (ng/mL); ULOQ=5000 ng/mL; sample times Day 1 and Day 43=0 h predose, 1.5, 3.0, 3.5, 5,5, 9.5, 24, 48 h postdose. Dacarbazine (DTIC) and AIC determined from plasma using liquid chromatography API tandem mass spectrometry (LC-API/MS/MS) detection; LLOQ for dacarbazine=10.0 ng/mL; ULOQ=5000 ng/mL; AIC LLOQ=0.05 µg/mL; ULOQ=25.0 µg/mL; sample times Day 1: 0 h predose, 1, 1.5, 2.5, 3.5, 5.5, 9.5, 24 h post dose.. (NCT00796991)
Timeframe: Day 1 (0 h) to Day 43

,,
InterventionmL/h (Geometric Mean)
CLT of Ipilimumab N=14, 14, 12CLT of Paclitaxel (Day 1) N=20, 0, 0CLT of Paclitaxel (Day 43) N=14, 0, 0CLT of Dacarbazine (Day 1) N=0, 19, 0CLT of Dacarbazine (Day 43) N=0, 16, 0CLT of AIC (Day 1) N=0, 19, 0CLT of AIC (Day 43) N=0, 17, 0
Dacarbazine, Ipilimumab11.17NANA34.3337.0991.6788.75
Ipilimumab10.23NANANANANANA
Paclitaxel, Carboplatin, Ipilimumab11.6327.8725.44NANANANA

[back to top]

Change From Baseline to Cycle 5 in Neuropathy Assessed by Treatment-specific Adverse Events Scale

The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5. (NCT00798603)
Timeframe: Baseline and Cycle 5

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab0

[back to top]

Proportion of Confirmed Tumor Response Defined as an Objective Status of Complete Response or Partial Response on Two Consecutive Evaluations

"Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:~Complete Response (CR): disappearance of all target and non-target lesions and no new lesions.~Partial Response (PR): disappearance of all target lesions, persistence of one or more non-target lesions, and no new lesions; or at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD, no appearance of one/more new lesions, unequivocal progression of existing non-target lesions, and no new lesions." (NCT00798603)
Timeframe: Duration of study until progression (up to 5 years)

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin + Bevacizumab40

[back to top]

Change From Baseline to Cycle 3 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale

Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3. (NCT00798603)
Timeframe: Baseline and Cycle 3

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab1.1

[back to top]

Change From Baseline to Cycle 3 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)

The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3. (NCT00798603)
Timeframe: Baseline and Cycle 3

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab0

[back to top]

Change From Baseline to Cycle 3 in Nausea Assessed by Treatment-specific Adverse Events Scale

The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3. (NCT00798603)
Timeframe: Baseline and Cycle 3

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab0

[back to top]

Change From Baseline to Cycle 5 in Fatigue Assessed by Treatment-specific Adverse Events Scale

The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5. (NCT00798603)
Timeframe: Baseline and Cycle 5

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab-10

[back to top]

Change From Baseline to Cycle 5 in Nausea Assessed by Treatment-specific Adverse Events Scale

The single-item nausea question was on a 10-points scale with 0=no nausea and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5. (NCT00798603)
Timeframe: Baseline and Cycle 5

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab0

[back to top]

Change From Baseline to Cycle 3 in Fatigue Assessed by Treatment-specific Adverse Events Scale

The single-item fatigue question was on a 10-points scale with 0=no fatigue and 10=as bad as you can imagine. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3. (NCT00798603)
Timeframe: Baseline and Cycle 3

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab0

[back to top]

Change From Baseline to Cycle 5 in Overall Quality of Life Assessed by Linear Analogue Self Assessment (LASA)

The overall quality of life (QOL) question was on a 10-points scale with 0=as bad as it can be and 10=as good as it can be. The QOL scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5. (NCT00798603)
Timeframe: Baseline and Cycle 5

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab0

[back to top]

Change From Baseline to Cycle 3 in Neuropathy Assessed by Treatment-specific Adverse Events Scale

The single-item neuropathy question was on a 10-points scale with 0=no numbness or tingling in fingers and toes and 10=worst numbness or tingling in fingers and toes imaginable. The item scores was translated onto a 0 to 100 point scale, with lower values indicating worse symptoms. Change from baseline to cycle 3 was calculated by subtracting the baseline scores from the scores at cycle 3. (NCT00798603)
Timeframe: Baseline and Cycle 3

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab0

[back to top]

Progression-free Survival

Progression-free survival was defined as the time from study enrollment to the first date of disease progression or death as a result of any cause, whichever occurs first. Progression-free survival will be censored at the date of the last contact for patients who are still alive and who have not had disease progression. (NCT00798603)
Timeframe: Up to 5 years

Interventionmonths (Median)
Pemetrexed + Carboplatin + Bevacizumab7

[back to top]

Number of Grade 3 or Higher Adverse Events Occurring in >=10% of Patients

Adverse events were assessed by Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Grading: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Life-threatening, Grade 5=Death. (NCT00798603)
Timeframe: Up to 2.5 years

Interventionparticpants (Number)
FatigueHypertensionNeutropeniaThrombocytopenia
Pemetrexed + Carboplatin + Bevacizumab1671811

[back to top]

Overall Survival

Overall survival was defined as the time from study enrollment to the time of death from any cause. Overall survival will be censored at the date of the last follow-up visit for patients who are still alive or lost to follow-up. (NCT00798603)
Timeframe: Up to 5 years

Interventionmonths (Median)
Pemetrexed + Carboplatin + Bevacizumab13.7

[back to top]

Progression-free Survival at 6 Months

Estimated using the Binomial point estimator (number of successes divided by the total number of evaluable patients). A patient is classified as a success if alive and progression-free at 6 months. (NCT00798603)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin + Bevacizumab60

[back to top]

Duration of Response

Duration of response for responders was defined as the time from the date of the first objective status assessment of a confirmed CR or PR to the first date of disease progression. Duration of response will be censored at the date of last post-therapy follow-up visit for responders who have not had disease progression. Duration of response will be calculated for all evaluable patients who have achieved an objective confirmed response. (NCT00798603)
Timeframe: Up to 5 years

Interventionmonths (Median)
Pemetrexed + Carboplatin + Bevacizumab8.8

[back to top]

Change From Baseline to Cycle 5 in Quality of Life (QOL) as Assessed by the Lung Cancer Symptom Scale

Lung Cancer Symptom Scale (LCSS) consist of 9 items that assess the symptoms of lung cancer during the past days on a 10-points scale with 0 as no symptoms and 10 as worse symptoms. The individual item score was translated onto a 0-100 point scale with lower values indicating worse symptoms. An average of the aggregate score of all 9 items was used for a total score. Change from baseline to cycle 5 was calculated by subtracting the baseline scores from the scores at cycle 5. (NCT00798603)
Timeframe: Baseline and Cycle 5

Interventionunits on a scale (Median)
Pemetrexed + Carboplatin + Bevacizumab1.1

[back to top]

Time to Treatment Failure

Time to treatment failure was defined to be the time from date of registration to the date at which the patient is removed from the treatment due to progression, toxicity, refusal or death from any cause. (NCT00798603)
Timeframe: Up to 5 years

Interventionmonths (Median)
Pemetrexed + Carboplatin + Bevacizumab4.89

[back to top]

Probability of Being Alive at 12 and 18 Months

(NCT00800202)
Timeframe: Months 12 and 18

,
Interventionpercent (Number)
12 Months18 Months
Bevacizumab+Erlotinib50.041.7
Bevacizumab+Paclitaxel+Carboplatin64.243.3

[back to top]

Percentage of Participants Achieving Progression-Free Survival (PFS) Without Disease Progression or Death at 6 Months

Tumor progression was defined according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm. (NCT00800202)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Bevacizumab+Paclitaxel+Carboplatin56.5
Bevacizumab+Erlotinib57.2

[back to top]

Percentage of Participants Achieving a Best Overall Response of Complete Response or Partial Response as Assessed by the Investigator Using RECIST

Overall response defined as best response according to RECIST recorded from date of randomization until disease progression or recurrence. Complete Response (CR): disappearance of all target lesions; Partial response (PR): reduction by at least 30 percent (%) of sum of the longest diameters of each target lesion, taking initial sum of longest diameters as a reference. Participants with a missing response were considered non-responders. 95% CI for one sample binomial using Pearson-Clopper method. (NCT00800202)
Timeframe: Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant

Interventionpercentage of participants (Number)
Bevacizumab+Paclitaxel+Carboplatin62.7
Bevacizumab+Erlotinib12.5

[back to top]

Percentage of Participants Who Died

(NCT00800202)
Timeframe: Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death

Interventionpercentage of participants (Number)
Bevacizumab+Paclitaxel+Carboplatin83.6
Bevacizumab+Erlotinib91.7

[back to top]

Percentage of Participants With Disease Progression or Death

Tumor progression was defined according to the RECIST criteria as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. PFS (investigator assessed) was defined as the time between the first dose of study treatment and the first event of progression or death by any cause. Participants without an event were censored the last time they were known to be progression free. PFS was analyzed using the Kaplan-Meier method in each treatment arm. (NCT00800202)
Timeframe: Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant

Interventionpercentage of participants (Number)
Bevacizumab+Paclitaxel+Carboplatin89.6
Bevacizumab+Erlotinib91.7

[back to top]

Time to Death

Time to death was determined as the number of months between the first dose of study treatment and the event of death by any cause. Overall survival was analyzed using the Kaplan-Meier method. (NCT00800202)
Timeframe: Day 1 of Cycles 1, 2, 3, 4, 5, 6 and every 3 weeks up to 18 months or until death

Interventionmonths (Median)
Bevacizumab+Paclitaxel+Carboplatin16.0
Bevacizumab+Erlotinib12.0

[back to top]

Time to Disease Progression or Death

Tumor progression was defined as increase by at least 20% in the sum of the longest diameters of each target lesion, taking as a reference the smallest sum of the longest diameters, reported since the start of treatment, or appearance of one or more new lesions. Time to event was determined as the number of months between the first dose of study treatment and the first event of progression or death by any cause. PFS was analyzed using the Kaplan-Meier method in each treatment arm. (NCT00800202)
Timeframe: Screening, Day 1 of Cycles 3 and 5 and every 2 cycles until end of treatment visit or disease progression or death up to 18 months after enrollment of last participant

Interventionmonths (Median)
Bevacizumab+Paclitaxel+Carboplatin6.7
Bevacizumab+Erlotinib6.3

[back to top]

Percentage of Participants With Progression-Free Survival Based on Radiologic and Clinical Assessments and Death After Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (based upon radiographic tumor assessments) or death. Disease progression was determined in accordance with the RECIST version 1.0 criteria. (NCT00806286)
Timeframe: 18 weeks postdose

Interventionpercentage of participants (Number)
CS7017+Carboplatin+Paclitaxel37.9
CS7017-matching Placebo+Carboplatin+Paclitaxel63.3

[back to top]

Percentage of Participants With Progression-Free Survival at 18 Weeks Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

Progression-free survival (PFS) was defined as the time from the date of randomization to the earlier of the dates of the first objective documentation of disease progression (based upon radiographic tumor assessments) or death. As per Response Evaluation Criteria for Solid Tumors v1.0, disease progression was characterized as confirmed complete response (CR) defined as disappearance of all target lesions, confirmed partial response (PR) defined as ≥30% decrease from baseline, stable disease (SD) defined as neither progressive disease (PD) nor PR, and PD defined as ≥20% increase from smallest sum of longest diameter recorded since treatment started. (NCT00806286)
Timeframe: 18 weeks postdose

Interventionpercentage of participants (Number)
CS7017+Carboplatin+Paclitaxel40.2
CS7017-matching Placebo+Carboplatin+Paclitaxel63.3

[back to top]

Summary of Kaplan-Meier Analysis of Overall Survival Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

Overall survival (OS) is defined as the time from randomization to the date of death resulting from any cause. (NCT00806286)
Timeframe: Baseline to date of death, up to approximately 2 years postdose

Interventiondays (Median)
CS7017+Carboplatin+Paclitaxel244.0
CS7017-matching Placebo+Carboplatin+Paclitaxel292.0

[back to top]

Number of Participants With Best Overall Tumor Response and Objective Response Rate Following Administration of Carboplatin/Paclitaxel With or Without CS-7017 in Chemotherapy-naïve Participants With Metastatic Non-small Cell Lung Cancer

As per Response Evaluation Criteria for Solid Tumors v1.0, the best overall response was characterized as confirmed complete response (CR) defined as disappearance of all target lesions, confirmed partial response (PR) defined as ≥30% decrease from baseline, stable disease (SD) defined as neither progressive disease (PD) nor PR, and PD defined as ≥20% increase from smallest sum of longest diameter recorded since treatment started. Objective response rate (ORR) was defined as CR + PR. (NCT00806286)
Timeframe: Baseline to disease progression, death, or withdrawal from study, up to approximately 2 years postdose

,
InterventionParticipants (Count of Participants)
Confirmed complete response (CR)Confirmed partial response (PR)Objective response (Confirmed CR+PR)Stable disease (SD)Progressive disease (PD)UnknownBest Objective Response of SD or Better
CS7017-matching Placebo+Carboplatin+Paclitaxel01616185742
CS7017+Carboplatin+Paclitaxel011111117829

[back to top] [back to top]

Number of Participants With Recurrence or Death Events at Primary Analysis

Recurrence-Free Survival is the period from study entry until disease recurrence, death, or date of last contact (NCT00807768)
Timeframe: Within 4 weeks after completing or discontinuing study therapy, then every 6 months for 2 years, then annually for 3 years, then as clinically indicated, assessed up to 10 years

InterventionParticipants (Count of Participants)
Arm I (Pelvic Radiation Therapy)44
Arm II (Brachytherapy, Paclitaxel, Carboplatin)43

[back to top]

Number of Participants With Sites of Recurrence

Three competing risk analyses were carried out for three different types of recurrences: 1) any vaginal, 2) any pelvic or any PA nodes and 3) any distant. More than one type of recurrence can be counted for an individual patient. A death prior to a specific type of recurrence was considered a competing event. (NCT00807768)
Timeframe: Within 4 weeks after completing or discontinuing study therapy, then every 6 months for 2 years, then annually for 3 years, then as clinically indicated thereafter, up to 10 years

,
InterventionParticipants (Count of Participants)
Vaginal recurrencePelvic or PA nodeDistant recurrence
Arm I (Pelvic Radiation Therapy)61247
Arm II (Brachytherapy, Paclitaxel, Carboplatin)62547

[back to top]

Patient Reported Fatigue

Patient reported fatigue as measured with the Functional Assessment of Chronic Illness Therapy- Fatigue scale (FACIT-Fatigue). The FACIT-Fatigue contains 13 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Fatigue score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The FACIT-Fatigue score ranges 0-52 with a large score suggests less fatigue. (NCT00807768)
Timeframe: Prior to study treatment (baseline), 4 weeks post the starting of study treatment, 10-11 weeks post the starting of study treatment, 8 months post the starting of study treatment, 14 months post the starting of study treatment

,
Interventionunits on a scale (Least Squares Mean)
Baseline4 Weeks10-11 Weeks8 Months14 Months
Arm I (Pelvic Radiation Therapy)40.535.840.542.140.9
Arm II (Brachytherapy, Paclitaxel, Carboplatin)41.235.836.840.341.1

[back to top]

Patient-reported Neurotoxicity

Patient reported neurotoxicity symptoms as measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggesting less neurotoxicity. (NCT00807768)
Timeframe: Prior to study treatment (baseline), 4 weeks post the starting of study treatment, 10-11 weeks post the starting of study treatment, 8 months post the starting of study treatment, 14 months post the starting of study treatment.

,
Interventionunits on a scale (Least Squares Mean)
Baseline4 Weeks10-11 Weeks8 Months14 Months
Arm I (Pelvic Radiation Therapy)14.614.614.214.013.5
Arm II (Brachytherapy, Paclitaxel, Carboplatin)14.713.012.012.712.8

[back to top]

Patient-reported Quality of Life

Patient reported quality of life as measured with the Treatment Outcome Index of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). The FACT-En TOI is a scale for assessing general QOL of endometrial cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Endometrium Cancer subscale (16 items). Each item in the FACT-En TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). . The FACT-En TOI score is calculated as the sum of the subscale scores if more than 80% of the FACT-En TOI items provide valid answers and all of the component subscales have valid scores. The FACT-En TOI score ranges 0-120 with a large score suggests better QOL (NCT00807768)
Timeframe: Prior to study treatment (baseline), 4 weeks post the starting of study treatment, 10-11 weeks post the starting of study treatment, 8 months post the starting of study treatment, 14 months post the starting of study treatment

,
Interventionunits on a scale (Least Squares Mean)
Baseline4 Weeks10-11 Weeks8 Months14 Months
Arm I (Pelvic Radiation Therapy)98.591.098.7101.599.7
Arm II (Brachytherapy, Paclitaxel, Carboplatin)98.792.295.699.9102.1

[back to top]

Number of Participants With Death Events

The number of death events is reported. Overall survival is reported by the number of deaths occurring while on study. (NCT00807768)
Timeframe: Overall survival is measured from study enrollment for up to 10 years.

InterventionParticipants (Count of Participants)
Arm I (Pelvic Radiation Therapy)39
Arm II (Brachytherapy, Paclitaxel, Carboplatin)37

[back to top]

Part D: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State.

AUCt,ss: Area under the concentration-time curve of Afatinib at steady state. (NCT00809133)
Timeframe: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

Interventionng*h/mL (Geometric Mean)
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)326
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)454
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)506
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)119

[back to top]

Part D: Carboplatin Cmax in Cycle 1 and 2

Maximum measured concentration of Carboplatin in plasma. (NCT00809133)
Timeframe: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

,,,
Interventionng/mL (Geometric Mean)
Cycle 1 (N=5, 7, 5, 7)Cycle 2 (N=8, 5, 2, 5)
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)1620017800
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)1850021500
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)1790018600
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)1560012800

[back to top]

Part D: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 23 Hours in Cycle 1 and Cycle 2

AUC0-23: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 23 hours. (NCT00809133)
Timeframe: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 23:00.

,,,
Interventionng*h/mL (Geometric Mean)
Cycle 1 (N=5, 7, 5, 6)Cycle 2 (N=8, 5, 2, 4)
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)1040010700
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)102009270
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)1300014800
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)922011900

[back to top]

Part D: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours. (NCT00809133)
Timeframe: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00

,,,
Interventionng*h/mL (Geometric Mean)
Cycle 1 (N=5, 7, 5, 7)Cycle 2 (N=8, 5, 2, 5)
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)6970065400
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)8100090300
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)6490074800
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)6870072100

[back to top]

Part C: Carboplatin Cmax in Cycle 1 and Cycle 2

Maximum measured concentration of Carboplatin in plasma. (NCT00809133)
Timeframe: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00

,
Interventionng/mL (Geometric Mean)
Cycle 1 (N=3, 9)Cycle 2 (N=3, 6)
Part C: A20C6 (Afatinib + Carboplatin)1510015200
Part C: A40C6 (Afatinib + Carboplatin)2110019600

[back to top]

Number of Participants With Dose Limiting Toxicities (DLTs) in the First Cycle for the Determination of the Maximum Tolerated Dose (MTD)

Dose limiting toxicity (DLT) was defined as an Adverse Event (AE) or laboratory abnormality considered as related to study treatment. (NCT00809133)
Timeframe: Cycle 1: 21 days (part C and D) or 28 days (part A and B)

InterventionParticipants (Number)
Part A: A20P80 (Afatinib + Paclitaxel)0
Part A: A40P80 (Afatinib + Paclitaxel)0
Part A: A50P80 (Afatinib + Paclitaxel)2
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)0
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)2
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)2
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)1
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)1
Part C: A20C6 (Afatinib + Carboplatin)0
Part C: A40C6 (Afatinib + Carboplatin)1
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)0
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)2
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)2
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)2

[back to top]

Maximum Tolerated Dose (MTD)

"The MTD of afatinib in selected combination treatments was defined as the highest dose at which no more than 1 out of 6 patients experienced DLTs during the first treatment cycle, i.e. the highest dose with a DLT incidence ≤17%. The MTD was determined separately for Afatinib in combination with Paclitaxel (part A), Afatinib in combination with Paclitaxel and Bevacizumab (part B), Afatinib and Carboplatin (part C), and Afatinib in combination with Paclitaxel and Carboplatin (part D).~In part C, dose escalation was not continued beyond the dose level A40C6, due to safety and pharmacokinetic considerations and upon mutual agreement between the investigators and the sponsor. Formally, no MTD was determined, however a recommended phase II dose was determined and is presented here.~0=not maximum tolerated dose, 1=is maximum tolerated dose~Note, the depicted order of treatment groups is driven by dose level, not by the actual dosing steps." (NCT00809133)
Timeframe: Cycle 1: 21 days (part C and D) or 28 days (part A and B)

InterventionUnits on a scale (Number)
Part A: A20P80 (Afatinib + Paclitaxel)0
Part A: A40P80 (Afatinib + Paclitaxel)1
Part A: A50P80 (Afatinib + Paclitaxel)0
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)0
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)0
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)0
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)0
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)1
Part C: A20C6 (Afatinib + Carboplatin)0
Part C: A40C6 (Afatinib + Carboplatin)1
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)1
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)0
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)0
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)0

[back to top]

Part D: Paclitaxel Cmax in Cycle 1 and 2

Maximum measured concentration of Paclitaxel in plasma. (NCT00809133)
Timeframe: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00

,,,
Interventionng/mL (Geometric Mean)
Cycle 1 (N=5, 7, 5, 6)Cycle 2 (N=8, 5, 2, 4)
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)37103620
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)30202590
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)42304850
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)25703290

[back to top]

Part A: Afatinib Cmax,ss on Day 15

Maximum measured concentration of Afatinib in plasma at steady state. (NCT00809133)
Timeframe: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

Interventionng/mL (Geometric Mean)
Part A: A20P80 (Afatinib + Paclitaxel)12.3
Part A: A40P80 (Afatinib + Paclitaxel)46.0
Part A: A50P80 (Afatinib + Paclitaxel)63.5

[back to top]

Part D: Afatinib Cmax,ss

Maximum measured concentration of Afatinib in plasma at steady state. (NCT00809133)
Timeframe: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

Interventionng/mL (Geometric Mean)
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)18.3
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)27.3
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)28.1
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)6.73

[back to top]

Part C: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State in Cycle 2

AUCt,ss: Area under the concentration-time curve of Afatinib in plasma at steady state. (NCT00809133)
Timeframe: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

Interventionng*h/mL (Geometric Mean)
Part C: A20C6 (Afatinib + Carboplatin)511
Part C: A40C6 (Afatinib + Carboplatin)465

[back to top]

Objective Tumour Response (Confirmed)

"Number of subjects with confirmed objective tumour response.~Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR). Objective response was to be confirmed by a second tumour assessment at least 4 weeks after the assessment of CR or PR." (NCT00809133)
Timeframe: From first drug administration until the last trial drug administration, up to 1156 days.

,,,,,,,,,,,,,
InterventionParticipants (Number)
Objective response: NoObjective response: Yes
Part A: A20P80 (Afatinib + Paclitaxel)30
Part A: A40P80 (Afatinib + Paclitaxel)34
Part A: A50P80 (Afatinib + Paclitaxel)51
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)80
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)30
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)51
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)50
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)52
Part C: A20C6 (Afatinib + Carboplatin)21
Part C: A40C6 (Afatinib + Carboplatin)72
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)42
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)70
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)71
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)32

[back to top]

Incidence and Intensity of AEs According to the Maximum Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grade

Incidence and Intensity of AEs (Adverse Events) graded according to the maximum CTCAE (Common Toxicity Criteria for Adverse Events) grade based on the number of patients with AEs with CTCAE Grade 1-5. (NCT00809133)
Timeframe: From first drug administration until the end of treatment cycle 1; 21 days (part C and D) or 28 days (part A and B)

,,,,,,,,,,,,,
InterventionParticipants (Number)
Grade 1Grade 2Grade 3Grade 4Grade 5
Part A: A20P80 (Afatinib + Paclitaxel)02010
Part A: A40P80 (Afatinib + Paclitaxel)02500
Part A: A50P80 (Afatinib + Paclitaxel)03300
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)03401
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)01200
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)00600
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)02201
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)01312
Part C: A20C6 (Afatinib + Carboplatin)00111
Part C: A40C6 (Afatinib + Carboplatin)02430
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)01311
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)02320
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)00620
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)01400

[back to top]

Part A: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

Area under the concentration-time curve of Afatinib in plasma at steady state. (NCT00809133)
Timeframe: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

Interventionng*h/mL (Geometric Mean)
Part A: A20P80 (Afatinib + Paclitaxel)250
Part A: A40P80 (Afatinib + Paclitaxel)813
Part A: A50P80 (Afatinib + Paclitaxel)939

[back to top]

Part B: Afatinib Cmax,ss on Day 15

Maximum measured concentration of Afatinib in plasma at steady state. (NCT00809133)
Timeframe: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00 and 24:00.

Interventionng/mL (Geometric Mean)
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)20.4
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)21.4
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)50.4
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)22.8
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)9.75

[back to top]

Part B: AUCt,ss: Area Under the Concentration-Time Curve of Afatinib in Plasma at Steady State on Day 15

Area under the concentration-time curve of Afatinib in plasma at steady state. (NCT00809133)
Timeframe: Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. There were no analyzable patients for Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab.

Interventionng*h/mL (Geometric Mean)
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)312
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)829
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)336
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)142

[back to top]

Part C: Area Under the Concentration-Time Curve of Carboplatin in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours in Cycle 1 and Cycle 2

AUC0-24: Area under the concentration-time curve of Carboplatin in plasma over the time interval from zero extrapolated to 24 hours. (NCT00809133)
Timeframe: Cycle 1, day 1 and cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 24:00.

,
Interventionng*h/mL (Geometric Mean)
Cycle 1 (N=3, 9)Cycle 2 (N=3, 6)
Part C: A20C6 (Afatinib + Carboplatin)7750077600
Part C: A40C6 (Afatinib + Carboplatin)7680075700

[back to top]

Part B: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From 0 Extrapolated Upto 24 Hours on Day 1 and Day 15

AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours. (NCT00809133)
Timeframe: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

,,,,
Interventionng*h/mL (Geometric Mean)
Day 1Day 15
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)3540NA
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)3760NA
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)38105290
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)3330NA
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)50904060

[back to top]

Part B: Bevacizumab Plasma Concentration

Bevacizumab plasma concentration after infusion of Bevacizumab 5mg/kg after end of 1st and 2nd infusion in Cycle 1. (NCT00809133)
Timeframe: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

Interventionμg/mL (Median)
Part B: End of 1st Infusion of Cycle 1119
Part B: End of 2nd Infusion of Cycle 1154

[back to top]

Part C: Afatinib Cmax,ss in Cycle 2

Maximum measured concentration of Afatinib in plasma at steady state. (NCT00809133)
Timeframe: Cycle 2, day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00 and 24:00.

Interventionng/mL (Geometric Mean)
Part C: A20C6 (Afatinib + Carboplatin)41.7
Part C: A40C6 (Afatinib + Carboplatin)44.2

[back to top]

Part A: Paclitaxel Cmax on Day 1 and Day 15

Maximum measured concentration of Paclitaxel in plasma. (NCT00809133)
Timeframe: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

,,
Interventionng/mL (Geometric Mean)
Day 1Day 15
Part A: A20P80 (Afatinib + Paclitaxel)4281880
Part A: A40P80 (Afatinib + Paclitaxel)20901590
Part A: A50P80 (Afatinib + Paclitaxel)14802120

[back to top]

Part A: AUC0-24: Area Under the Concentration-Time Curve of Paclitaxel in Plasma Over the Time Interval From Zero Extrapolated to 24 Hours on Day 1 and Day 15

AUC0-24: Area under the concentration-time curve of Paclitaxel in plasma over the time interval from zero extrapolated to 24 hours. (NCT00809133)
Timeframe: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

,,
Interventionng*h/mL (Geometric Mean)
Day 1 (N=3, 6, 5)Day 15 (N=3, 6, 5)
Part A: A20P80 (Afatinib + Paclitaxel)19703560
Part A: A40P80 (Afatinib + Paclitaxel)37303170
Part A: A50P80 (Afatinib + Paclitaxel)32603950

[back to top]

Objective Tumour Response (Unconfirmed)

"Number of subjects with objective tumour response (unconfirmed).~Objective Response (OR) was defined as Complete Response (CR) or Partial Response (PR)." (NCT00809133)
Timeframe: From first drug administration until the last trial drug administration, up to 1156 days.

,,,,,,,,,,,,,
InterventionParticipants (Number)
Objective response: NoObjective response: Yes
Part A: A20P80 (Afatinib + Paclitaxel)30
Part A: A40P80 (Afatinib + Paclitaxel)34
Part A: A50P80 (Afatinib + Paclitaxel)51
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)71
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)30
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)51
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)41
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)52
Part C: A20C6 (Afatinib + Carboplatin)21
Part C: A40C6 (Afatinib + Carboplatin)72
Part D: A20P175C5 ( Afatinib + Paclitaxel + Carboplatin)42
Part D: A20P175C6 (Afatinib + Paclitaxel + Carboplatin)61
Part D: A30P175C5 (Afatinib + Paclitaxel + Carboplatin)62
Part D: A40P175C5 (Afatinib + Paclitaxel + Carboplatin)23

[back to top]

Part B: Paclitaxel Cmax on Day 1 and Day 15

Maximum measured concentration of Paclitaxel in plasma. (NCT00809133)
Timeframe: Day 1: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00. Day 15: -0:05 (hh:mm), 0:00, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 24:00.

,,,,
Interventionng/mL (Geometric Mean)
Day 1Day 15
Part B: A20P80B10 (Afatinib + Paclitaxel + Bevacizumab)17502120
Part B: A20P80B5 (Afatinib + Paclitaxel + Bevacizumab)18001490
Part B: A20P80B7.5 (Afatinib + Paclitaxel + Bevacizumab)19202730
Part B: A30P80B5 (Afatinib + Paclitaxel + Bevacizumab)17001550
Part B: A40P80B5 (Afatinib + Paclitaxel + Bevacizumab)29501620

[back to top]

Proportion of Patients Experiencing Grade 3 or 4 Diarrhea as Measured by NCI CTCAE v3.0

(NCT00820872)
Timeframe: Up to 10 years

Interventionpercentage of patients (Number)
Group 143

[back to top]

Overall Survival

Defined as the time between Day 1 Cycle 1 to date of death from any cause. (NCT00821886)
Timeframe: approximately 48 months

Interventionmonths (Number)
Ixabepilone/Trastuzumab/CarboplatinNA

[back to top]

Pathologic Complete Response (pCR)

Proportion of patients who do not exhibit residual invasive breast cancer in breast or axillary lymph nodes at time of surgery (NCT00821886)
Timeframe: average18 months

Interventionparticipants (Number)
Ixabepilone/Trastuzumab/Carboplatin27

[back to top]

Number of Subjects With Adverse Events as a Measure of Safety and Toxicity

Assessment based on the frequency of treatment-related adverse events according to NCI CTCAE criteria v3.0. (NCT00821886)
Timeframe: Day 1 of each 3 week cycle up to 6 cycles , and every 9 weeks post-surgery until treatment discontinuation

Interventionparticipants (Number)
FatigueAnemiaNeutropeniaPeripheral neuropathyLeukopeniaNauseaThrombocytopeniaAlopeciaDiarrheaConstipationAnorexiaVomitingArthralgiaDyspneaMyalgiaPain - extremityDysgeusiaGERDRashEdemaFebrile neutropenia
Ixabepilone/Trastuzumab/Carboplatin54504947464540262521191816141414131313124

[back to top]

Disease-free Survival

Defined as the interval from the first date of study treatment until the date of tumor recurrence or death from any cause (NCT00821886)
Timeframe: expected average 18 months

Interventionmonths (Median)
Ixabepilone/Trastuzumab/CarboplatinNA

[back to top]

Overall Survival

Overall survival was defined as the time from the study registration until death from any cause. Patients who were alive or lost to follow-up at the time of analysis were censored at date last known alive. (NCT00828009)
Timeframe: Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years

Interventionmonths (Median)
Step 2 - Maintenance Therapy42.7

[back to top]

Proportion of Patients With Target Adverse Events for the Step 2 Treatment

The study is to evaluate the safety of the combination of tecemotide immunotherapy with bevacizumab. The target adverse events for the combined treatment are as follows: grade 4-5 hemorrhage, esophagitis, fistula, platelet count decrease (thrombocytopenia), encephalitis infection, or hepatic failure episodes. (NCT00828009)
Timeframe: Assessed every 3 weeks while on treatment and up to 5 years

Interventionproportion of participants (Number)
Step 2 - Maintenance Therapy0.03

[back to top]

Progression-free Survival

"Progression-free survival was defined as the time from study registration to disease progression or death from any cause, whichever came first. If date of death was greater than 3 months after date of last disease assessment that showed progression-free, the patient was censored at the time of last disease assessment. Patients alive and without documented progression were censored at the date last known progression-free.~Progression is defined using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria (version 1.1), as at least 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, the appearance of new lesions, or unequivocal progression of existing non-target lesions." (NCT00828009)
Timeframe: Every 3 months for patients < 2 years from study entry, and every 6 months if patient is 2-5 years from study entry; up to 5 years

Interventionmonths (Median)
Step 2 - Maintenance Therapy14.9

[back to top]

Overall Survival by Treatment Arm

(NCT00828841)
Timeframe: Survival was measured from the date of randomization to date of death due to any cause, assessed up to 36 months. Subjects who were alive at the date of last contact were censored at the date of last contact.

InterventionMonths (Median)
Paclitaxel, Carboplatin, Cetuximab (Arm A)9.5
Platinum, Gemcitabine, Cetuximab (Arm B)8.3
Platinum, Pemetrexed, Cetuximab (Arm C)10.6

[back to top]

Overall Survival by Histology

(NCT00828841)
Timeframe: Survival was measured from the date of randomization to date of death due to any cause, assessed up to 36 months. Subjects who were alive at the date of last contact were censored at the date of last contact.

InterventionMonths (Median)
Squamous Cell Histology8.7
Non-squamous Cell Histology9.9

[back to top]

1-year Survival by Treatment Arm

(NCT00828841)
Timeframe: Survival was measured from the date of randomization to date of death due to any cause, assessed up to 36 months. Subjects who were alive at the date of last contact were censored at the date of last contact.

Interventionpercentage of participants (Number)
Paclitaxel, Carboplatin, Cetuximab (Arm A)39.7
Platinum, Gemcitabine, Cetuximab (Arm B)37.2
Platinum, Pemetrexed, Cetuximab (Arm C)47.3

[back to top]

Maximum Tolerated Dose (MTD)

Tolerability was confirmed by the frequency of occurrence of Dose Limiting Toxicities (DLTs) observed by the end of Cycle 1 in 6 participants. (NCT00832819)
Timeframe: 7 days during the run-in period (Cycle 0) and 3 weeks (21 days) from Cycle 1

Interventionmg BID (Number)
E7080 6 mg BID (Dose Escalation)4

[back to top]

Maximum Plasma Concentration of MK-2206 (Cmax)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Cmax after Dose 1. The Cmax of MK-2206 after Dose 1 will be presented. (NCT00848718)
Timeframe: At designated time points on Cycle 1 Day 1 (Up to 96 hours)

Interventionnmol/L (Mean)
MK-2206 45 mg QOD+Carboplatin+Paclitaxel57.7
MK-2206 60 mg QOD+Carboplatin+Paclitaxel88.3
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel144
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel247
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel431
MK-2206 45 mg QOD+Docetaxel 75 mg/m^242.9
MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2106
MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2278
MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2287
MK-2206 45 mg QOD+Erlotinib 100 mg48.8
MK-2206 45 mg QOD+Erlotinib 150 mg65.6
MK-2206 135 mg QW+Erlotinib 100 mg212
MK-2206 135 mg QW+Erlotinib 150 mg244

[back to top]

Maximum Tolerated Dose (MTD) of MK-2206 Administered Every Other Day (QOD) in Combination With Carboplatin and Paclitaxel

Participants received MK-2206 (45 or 60 mg) administered PO on Days 1, 3, 5, and 7 in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a dose limiting toxicity (DLT). DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. (NCT00848718)
Timeframe: Cycle 1 (Up to 21 days)

Interventionmg (Number)
MK-2206 Administered QOD+Carboplatin+PaclitaxelNA

[back to top]

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT) During Cycle 1

A DLT was any of the following deemed drug related by investigator and graded using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria: Grade (G)4 hematologic toxicity lasting ≥7 days; G4 thrombocytopenia; G3 or 4 febrile neutropenia and/or infection requiring treatment; G3, 4, 5 non-hematologic toxicity(with the exception of G3 nausea, vomiting, diarrhea, dehydration, or hyperglycemia that as a result of inadequate compliance with supportive care measures; alopecia, inadequately treated hypersensitivity reactions G3 elevated transaminases of ≤1 week in duration); adverse experience (AE) leading to dose reduction; unresolved toxicity causing ≥3 week delay in treatment; ≥G3 hyperglycemia; persistent increases in QTc interval; clinically significant bradycardia; and missing MK-2206 doses due to toxicity. The number of participants who experienced a DLT is presented. (NCT00848718)
Timeframe: Cycle 1 (Up to 21 days)

InterventionParticipants (Count of Participants)
MK-2206 45 mg QOD+Carboplatin+Paclitaxel1
MK-2206 60 mg QOD+Carboplatin+Paclitaxel2
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel1
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel1
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel2
MK-2206 45 mg QOD+Docetaxel 75 mg/m^23
MK-2206 90 mg Q3W+Docetaxel 60 mg/m^20
MK-2206 135 mg Q3W+Docetaxel 60 mg/m^20
MK-2206 200 mg Q3W+Docetaxel 60 mg/m^21
MK-2206 45 mg QOD+Erlotinib 100 mg2
MK-2206 45 mg QOD+Erlotinib 150 mg1
MK-2206 135 mg QW+Erlotinib 100 mg0
MK-2206 135 mg QW+Erlotinib 150 mg1

[back to top]

Minimum Plasma Concentration of MK-2206 (Ctrough)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 Ctrough after Dose 1. The Ctrough after Dose 1 is presented and is the 48-hour postdose concentration. (NCT00848718)
Timeframe: At designated time points on Cycle 1 Day 1 (Up to 48 hours)

Interventionnmol/L (Mean)
MK-2206 45 mg QOD+Carboplatin+Paclitaxel24.9
MK-2206 60 mg QOD+Carboplatin+Paclitaxel40.6
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel1.36
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel4.67
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel2.21
MK-2206 45 mg QOD+Docetaxel 75 mg/m^217.1
MK-2206 90 mg Q3W+Docetaxel 60 mg/m^22.27
MK-2206 135 mg Q3W+Docetaxel 60 mg/m^23.80
MK-2206 200 mg Q3W+Docetaxel 60 mg/m^23.24
MK-2206 45 mg QOD+Erlotinib 100 mg23.8
MK-2206 45 mg QOD+Erlotinib 150 mg36.8
MK-2206 135 mg QW+Erlotinib 100 mg96.6
MK-2206 135 mg QW+Erlotinib 150 mg95.5

[back to top]

MTD of MK-2206 Administered Every Three Weeks (Q3W) in Combination With Carboplatin and Paclitaxel

Participants received MK-2206 (90, 135, or 200 mg) administered PO in combination with carboplatin AUC 6 and paclitaxel 200 mg/m^2 administered IV on Day 1 of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. (NCT00848718)
Timeframe: Cycle 1 (up to 21 days)

Interventionmg (Number)
MK-2206 Administered Q3W+Carboplatin+PaclitaxelNA

[back to top]

Time to Maximum Plasma Concentration of MK-2206 (Tmax)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48, 96h postdose) for the determination of MK-2206 Tmax after Dose 1. The Tmax of MK-2206 after Dose 1 will be presented. (NCT00848718)
Timeframe: At designated time points on Cycle 1 Day 1 (Up to 96 hours)

Interventionhours (Median)
MK-2206 45 mg QOD+Carboplatin+Paclitaxel4.0
MK-2206 60 mg QOD+Carboplatin+Paclitaxel8.0
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel6.0
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel10.0
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel5.0
MK-2206 45 mg QOD+Docetaxel 75 mg/m^26.0
MK-2206 90 mg Q3W+Docetaxel 60 mg/m^24.0
MK-2206 135 mg Q3W+Docetaxel 60 mg/m^26.0
MK-2206 200 mg Q3W+Docetaxel 60 mg/m^26.0
MK-2206 45 mg QOD+Erlotinib 100 mg6.0
MK-2206 45 mg QOD+Erlotinib 150 mg7.0
MK-2206 135 mg QW+Erlotinib 100 mg6.0
MK-2206 135 mg QW+Erlotinib 150 mg4.0

[back to top]

MTD of MK-2206 Administered Once Every Week (QW) in Combination With Erlotinib

Participants received MK-2206 135 mg administered PO on Days 1, 8 and 15 in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. (NCT00848718)
Timeframe: Cycle 1 (up to 21 days)

Interventionmg (Number)
MK-2206 Administered QW+ErlotinibNA

[back to top]

MTD of MK-2206 Administered Q3W in Combination With Docetaxel

Participants received MK-2206 (90, 135, or 200 mg) administered PO on Day 1 in combination with Docetaxel 60 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. (NCT00848718)
Timeframe: Cycle 1 (up to 21 days)

Interventionmg (Number)
MK-2206 Administered Q3W+DocetaxelNA

[back to top]

MTD of MK-2206 Administered QOD in Combination With Docetaxel

Participants received MK-2206 45 mg administered PO on Days 1, 3, 5, and 7 in combination with Docetaxel 75 mg/m^2 administered IV on Day 1 of each 21-day cycle. Participants also received an oral corticosteroid PO daily. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. (NCT00848718)
Timeframe: Cycle 1 (up to 21 days)

Interventionmg (Number)
MK-2206 Administered QOD+DocetaxelNA

[back to top]

MTD of MK-2206 Administered QOD in Combination With Erlotinib

Participants received MK-2206 45 mg administered PO every other day (Days 1, 3, 5, 7, 9, 11, 13, 15, 17, 19 and 21) in combination with Erlotinib (100 or 150 mg) administered PO once every day of each 21-day cycle. The MTD was determined by the number of participants who experienced a DLT. DLT was defined using the NCI CTCAE version 3.0 criteria. See primary DLT outcome measure for the DLT definition. The MTD was defined as the dose level, at which the percentage of patients who experienced a DLT rate in Cycle 1 that was closest to 30%. A minimum of 13 participants were required to be enrolled per dose to calculate DLT. If the DLT threshold or enrollment quota per dose were not reached then the MTD could not be determined. (NCT00848718)
Timeframe: Cycle 1 (up to 21 days)

Interventionmg (Number)
MK-2206 Administered QOD+ErlotinibNA

[back to top]

Number of Participants Who Had a Tumor Response of Complete Response (CR) or Partial Response (PR)

Tumor response was assessed using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) and was recorded from the start of the study treatment until the end of treatment. Response categories included: Complete Response (CR): disappearance of all target lesions and Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions. The number of participants who had a tumor response of either CR or PR is presented. (NCT00848718)
Timeframe: Up to approximately 4 months (6 cycles)

InterventionParticipants (Count of Participants)
MK-2206 45 mg QOD+Carboplatin+Paclitaxel1
MK-2206 60 mg QOD+Carboplatin+Paclitaxel3
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel0
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel1
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel1
MK-2206 45 mg QOD+Docetaxel 75 mg/m^20
MK-2206 90 mg Q3W+Docetaxel 60 mg/m^20
MK-2206 135 mg Q3W+Docetaxel 60 mg/m^20
MK-2206 200 mg Q3W+Docetaxel 60 mg/m^20
MK-2206 45 mg QOD+Erlotinib 100 mg0
MK-2206 45 mg QOD+Erlotinib 150 mg0
MK-2206 135 mg QW+Erlotinib 100 mg0
MK-2206 135 mg QW+Erlotinib 150 mg0

[back to top]

Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h)

Blood samples are to be collected at specified time points according to arm and schedule: QOD schedule for MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48 hours(h) postdose); Q3W schedule MK-2206+carboplatin+paclitaxel and MK-2206+docetaxel (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); QOD schedule for the MK-2206+erlotinib (Cycle 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose); and QW schedule for MK-2206+erlotinib (Cycles 1 Day 1: predose and 2, 4, 6, 10, 24, 48h postdose) for the determination of MK-2206 AUC0-48h after Dose 1. The AUC0-48h after Dose 1 is presented. (NCT00848718)
Timeframe: At designated time points on Cycle 1 Day 1 (Up to 48 hours)

Interventionnmol•hr/L (Mean)
MK-2206 45 mg QOD+Carboplatin+Paclitaxel1630
MK-2206 60 mg QOD+Carboplatin+Paclitaxel2700
MK-2206 90 mg Q3W+Carboplatin+Paclitaxel4130
MK-2206 135 mg Q3W+Carboplatin+Paclitaxel7420
MK-2206 200 mg Q3W+Carboplatin+Paclitaxel9730
MK-2206 45 mg QOD+Docetaxel 75 mg/m^21320
MK-2206 90 mg Q3W+Docetaxel 60 mg/m^23000
MK-2206 135 mg Q3W+Docetaxel 60 mg/m^28090
MK-2206 200 mg Q3W+Docetaxel 60 mg/m^27690
MK-2206 45 mg QOD+Erlotinib 100 mg1460
MK-2206 45 mg QOD+Erlotinib 150 mg2110
MK-2206 135 mg QW+Erlotinib 100 mg6420
MK-2206 135 mg QW+Erlotinib 150 mg6560

[back to top]

Progression-free Survival (PFS)

PFS was defined as the time (in months) from the date of randomization to the date of the first observation of progression based on the independent radiologic assessment (modified response evaluation criteria in solid tumors [RECIST]), or date of death, whatever the cause. As per RECIST, disease progression was defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. If progression or death was not observed for a participant, the PFS time was censored at the date of the last tumor assessment without evidence of progression before the date of initiation of further antitumor treatment, or the cutoff date (whichever was earlier). (NCT00849667)
Timeframe: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin9.5
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin9.7
Placebo Plus Taxane and Carboplatin9.0

[back to top]

Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

Interventionliter (Mean)
Total Carboplatin
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin28.20

[back to top]

Vd: Volume of Distribution of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

,
Interventionliter (Mean)
Total CarboplatinTotal Paclitaxel
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin20.30169.50
Placebo Plus Taxane and Carboplatin14.86110.23

[back to top]

T1/2: Terminal Half-life of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

,,
Interventionhours (Mean)
Total CarboplatinTotal Paclitaxel
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin2.941.55
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin1.644.82
Placebo Plus Taxane and Carboplatin1.724.78

[back to top]

Progression-Free Survival Based on Gynecologic Cancer InterGroup (GCIG) Criteria

"PFS using GCIG criteria was defined as time (in months) from date of randomization until date of first observation of progression based on GCIG criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, GCIG PFS time was censored at later date of last tumor assessment or CA-125 assessment without evidence of progression before date of initiation of further antitumor treatment or the primary analysis cut off date, whichever was earlier. Disease progression per GCIG: Participants with elevated CA-125 pretreatment and normalisation of CA-125 must show evidence of CA-125 >=two times ULN on two occasions at least one week apart or participants with elevated CA-125 pretreatment, which never normalises must show evidence of CA-125 >=two times nadir value on two occasions at least one week apart or participants with CA-125 in normal range pretreatment must show evidence of CA-125 >=two times ULN on two occasions at least one week apart." (NCT00849667)
Timeframe: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin8.8
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin8.6
Placebo Plus Taxane and Carboplatin8.4

[back to top]

AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

Interventionmicrogram hour per liter (mcg*h/L) (Mean)
Total Carboplatin
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin58.70

[back to top]

AUC (0-inf): Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

,
Interventionmicrogram hour per liter (mcg*h/L) (Mean)
Total CarboplatinTotal Paclitaxel
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin77.0512.30
Placebo Plus Taxane and Carboplatin70.3716.19

[back to top]

CL: Clearance of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

Interventionliter per hour (L/h) (Mean)
Total Carboplatin
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin6.65

[back to top]

Time to Tumor Response (TTR)

Time to tumor response was defined as the time (in months) from the date of randomization to first documentation of objective tumor response. Time to tumor response was derived for those participants with objective evidence of CR or PR. (NCT00849667)
Timeframe: From the date of randomization to first documentation of objective response (up to 48 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin1.5
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin1.5
Placebo Plus Taxane and Carboplatin1.5

[back to top]

CL: Clearance of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

,
Interventionliter per hour (L/h) (Mean)
Total CarboplatinTotal Paclitaxel
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin8.7724.80
Placebo Plus Taxane and Carboplatin7.2121.00

[back to top]

Cmax: Maximum Observed Plasma Concentration of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

,,
Interventionmicrogram per milliliter (mcg/mL) (Mean)
Total CarboplatinTotal Paclitaxel
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin19.303.29
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin43.553.86
Placebo Plus Taxane and Carboplatin21.724.95

[back to top]

Time to 50% Serologic Response (TSR)

TSR was defined as the time (in months) from the date of randomization to first documentation of 50% SR. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). (NCT00849667)
Timeframe: From the date of randomization to first documentation of 50% SR (up to 48 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin1.0
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin0.9
Placebo Plus Taxane and Carboplatin1.2

[back to top]

Percentage of Participants With Objective Response

Objective response was defined as either a confirmed complete response (CR) or confirmed partial response (PR) as assessed by investigator based on response evaluation criteria in solid tumors version 1.1 (RECIST version 1.1). CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. (NCT00849667)
Timeframe: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 48 months)

Interventionpercentage of participants (Number)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin57.6
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin58.2
Placebo Plus Taxane and Carboplatin55.8

[back to top]

Percentage of Participants With Length of Second Remission Greater Than First Remission

Length of first remission was defined as a.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy until date of first relapse (that is, first observation of progression). It was assumed that the date of first relapse was the earlier of progression by CA-125 or progression by radiologic assessment, as judged by the investigator using GCIG criteria. b.) the period of time (in months) from the date of completion of previous platinum-based chemotherapy (used prior to study entry) until date of randomization. The length of the second remission was defined as the period of time (in months) from the date of completion of platinum-based chemotherapy until the first observation of progression based on GCIG criteria. Based on GCIG criteria, disease progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the baseline sum of diameters of target lesions. (NCT00849667)
Timeframe: From the date of last dose of platinum-based chemotherapy to date of relapse and date of last dose of platinum-based chemotherapy to first observation of progression (up to 48 months)

Interventionpercentage of participants (Number)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin4.0
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin6.5
Placebo Plus Taxane and Carboplatin4.5

[back to top]

Percentage of Participants With Clinical Benefit

Clinical benefit was defined as a confirmed CR or a confirmed PR, or stable disease (SD) using RECIST 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions (non-lymph nodes). All pathological lymph nodes (whether target or non-target) must have a reduction in their short axis <10 mm. PR was defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference smallest sum of longest dimensions since treatment started associated to non-progressive disease response for non target lesions. (NCT00849667)
Timeframe: Up to 48 months

Interventionpercentage of participants (Number)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin68.9
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin66.4
Placebo Plus Taxane and Carboplatin64.6

[back to top]

Overall Survival (OS)

OS was defined as the time (in months) from the date of randomization to the date of death, due to any cause. If death was not observed for a participant, the survival time was censored on the last date the participant was known to be alive or the cutoff date, whichever was earlier. (NCT00849667)
Timeframe: From the date of randomization until date of death from any cause, or study termination by sponsor, whichever came first (up to 48 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin28.7
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin32.1
Placebo Plus Taxane and Carboplatin29.1

[back to top]

Duration of Tumor Response

Duration of response was defined as the time (in months) from first documentation of objective response (confirmed CR or PR) to the first documentation of objective tumor progression or death due to any cause. Duration of response was derived only for those participants with objective evidence of confirmed CR or PR. (NCT00849667)
Timeframe: From the first date of confirmed objective response (CR or PR) to first date of progression or death due to any cause (up to 48 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin8.0
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin8.9
Placebo Plus Taxane and Carboplatin7.6

[back to top]

Duration of 50% Serologic Response

Duration of SR was defined as the time (in months) from first documentation of response to the first documentation of 50% serologic progression or death due to any cause. For responding participants who did not have serologic progression or did not die and who 1) were either still on study at the time of an analysis, 2) were given antitumor treatment other than study treatment, or 3) were withdrawn from study follow-up before documentation of serologic progression, the duration of SR was censored at the last date the participant was known to be without serologic progression. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of three CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). (NCT00849667)
Timeframe: From the first date of documentation of response to first documentation of serologic progression or death due to any cause (up to 48 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin10.7
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin12.0
Placebo Plus Taxane and Carboplatin9.9

[back to top]

Cancer Antigen-125 (CA-125) Progression-Free Survival

"CA-125 PFS was defined as the time (in months) from the date of randomization until the date of the first observation of progression based on the Rustin criteria, or date of death, whatever the cause. If progression or death was not observed for a participant, the CA-125 PFS time was censored at the date of the last CA-125 assessment without evidence of progression before the date of initiation of further antitumor treatment or the primary analysis cut off date, whichever was earlier. Based on Rustin criteria, progressive disease (PD) was a rise in CA125 since beginning of consolidation or previously normal CA125 that rises to greater than or equal to (>=) 2 multiple (*) ULN with either event documented on two occasions or CA-125 >=2*nadir value with either event documented on two occasions." (NCT00849667)
Timeframe: From the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first (up to 44 months)

Interventionmonths (Median)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin13.2
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin18.1
Placebo Plus Taxane and Carboplatin12.0

[back to top]

Mean Functional Assessment of Cancer Therapy-Ovarian Treatment Outcome Index (FACT-O TOI) Scores

Participant-reported Quality of Life (QoL) was measured using the Functional Assessment of Cancer Therapy-Ovarian (FACT-O), version 4 and reported in the Treatment Outcome Index (TOI) format. TOI is a 26-item subset of the FACT-O questionnaire composed of the raw sum of the physical well-being subscale (7 items), the functional well-being subscale (7 items), and the ovarian cancer subscale (12 items). Each item was scored on a scale of 0 (not at all) to 4 (very much). Some items were reversed scored. Scores from each subsection were summed into one composite score, termed the FACT-O TOI score which ranged from 0 to 104 and a higher score reflected better QoL. As per planned analysis, farletuzumab treatment groups 1.25 mg/kg and 2.5 mg/kg were pooled for the QoL assessment. (NCT00849667)
Timeframe: Cycle 3, Cycle 6, Cycle 12 (each cycle length=21 days)

,
Interventionscore on a scale (Mean)
Cycle 3Cycle 6Cycle 12
All Participants: Farletuzumab69.670.176.2
Placebo Plus Taxane and Carboplatin70.770.772.9

[back to top]

Percentage of Participants With Serologic Response (SR)

SR was defined as either normalization, 75% response, or 50% response using the Rustin criteria. Percentage of participants with 50% SR, 75% SR and SR leading to normalization were reported. A 50% response according to CA-125 was defined as a 50% decrease in serum CA-125 levels, as determined through a series of four CA-125 samples (one baseline sample with an elevated level, the sample that showed a 50% decrease, and a confirmatory sample at the decreased level). A 75% response was established if there had a serial decrease in serum CA-125 levels of 75% over three samples. In both the 50% and 75% response definitions, the final sample was analyzed at least 28 days after the previous sample. (NCT00849667)
Timeframe: Up to 48 months

,,
Interventionpercentage of participants (Number)
50% SR (Responder)75% SR (Responder)SR leading to normalization (Responder)
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin91.986.165.2
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin97.485.764.8
Placebo Plus Taxane and Carboplatin92.382.059.9

[back to top]

Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) of Total Carboplatin and Total Paclitaxel

(NCT00849667)
Timeframe: Cycle 2 Week 1 Day 1: 0-45 hours post-dose (cycle length=21 days)

,,
Interventionhours (Median)
Total CarboplatinTotal Paclitaxel
1.25 mg/kg Farletuzumab Plus Taxane and Carboplatin0.753.00
2.5 mg/kg Farletuzumab Plus Taxane and Carboplatin0.793.21
Placebo Plus Taxane and Carboplatin1.963.00

[back to top]

Number of Patients With Adverse Events - Phase II

The degree of toxicity as defined by The National Cancer Institute Common Toxicity Criteria version 3. (NCT00856830)
Timeframe: 9 weeks

Interventionparticipants (Number)
Novel Drug Combination8

[back to top]

Progression Free Survival

Using the Response Evaluation Criteria in Solid Tumors (RECIST 2000), progression is defined as 20% or greater increase from the baseline tumor parameters or new lesions. (NCT00856830)
Timeframe: 7 months

Interventionmonths (Median)
Novel Drug Combination6.0

[back to top]

Number of Participants Experiencing Dose Limiting Toxicity Regimen A - Phase I

The determination of the dose limiting toxicity as defined by The National Cancer Institute Common Toxicity Criteria version 3 as follows: grade 4 neutropenia >5 days; grade 3/4 febrile neutropenia; grade 4 thrombocytopenia; or grade >2 non-hematologic toxicities (except for nausea/vomiting, alopecia, or fatigue). (NCT00856830)
Timeframe: 9 weeks

Interventionparticipants (Number)
Phase I - Cohort IPhase I - Cohort IIPhase I - Cohort III
Novel Drug Combination011

[back to top]

Overall Survival

Number of Participants who Died Due to Any Cause (NCT00861705)
Timeframe: up to 10 years

InterventionParticipants (Count of Participants)
Arm 1 (Pac --> ddAC)22
Arm 2 (Pac + Bev --> ddAC + Bev)26
Arm 3 (Pac + Carboplatin --> ddAC)30
Arm 4 (Pac + Carboplatin + Bev --> ddAC + Bev)24

[back to top]

Incidence and Severity of Post-op Complications, Namely Excessive Bleeding, Delayed Wound Healing, and Wound Dehiscence.

Assessed by physician observation. (NCT00861705)
Timeframe: at definitive surgery, up to 28 weeks

,
Interventionpercentage of participants with event (Number)
Excessive bleedingDelayed healingWound dehiscence
Factor B: Bevacizumab011
Factor B: No Bevacizumab000

[back to top]

Pathologic Complete Response (pCR) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is).

Assessment of the difference in percentage of participants with pCR in the breast between regimens that contain bevacizumab (arms 2&4) versus not (arms 1&3) will use a one-sided chi square test. 95% confidence intervals around the incidence of pCR will also be constructed using exact binomial methods. (NCT00861705)
Timeframe: At the time of definitive surgical removal, up to 28 weeks

Interventionpercentage of participants with pCR (Number)
Factor B: Bevacizumab59
Factor B: No Bevacizumab48

[back to top]

Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0).

Comparing regimens that contain carboplatin (arms 3&4) versus not (arms 1&2). (NCT00861705)
Timeframe: At the time of definitive surgical removal, up to 28 weeks

Interventionpercentage of participants with pCR (Number)
Factor A: Carboplatin54
Factor A: No Carboplatin41

[back to top]

Pathologic Complete Response (pCR) in the Breast and Axilla. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is) Plus the Absence of Any Tumor Deposit >0.2 mm in Sampled Axillary Nodes (ypT0/isN0).

Comparing regimens that contain bevacizumab (arms 2&4) versus not (arms 1&3). (NCT00861705)
Timeframe: At the time of definitive surgical removal, up to 28 weeks

Interventionpercentage of participants with pCR (Number)
Factor B: Bevacizumab52
Factor B: No Bevacizumab44

[back to top]

Pathologic Complete Response (pCR) in the Breast. Defined as the Absence of Residual Invasive Carcinoma in the Breast (ypT0/is).

Assessment of the difference in percentage of participants with pCR in the breast between regimens that contain carboplatin (arms 3&4) versus not (arms 1&2) will use a one-sided chi square test. 95% confidence intervals around the incidence of pCR will also be constructed using exact binomial methods. (NCT00861705)
Timeframe: At the time of definitive surgical removal, up to 28 weeks

Interventionpercentage of participants with pCR (Number)
Factor A: Carboplatin60
Factor A: No Carboplatin46

[back to top]

Pathologic Stage in the Breast and in the Breast Plus Axilla as Measured by American Joint Committee on Cancer (AJCC) Tumor Node Metastasis (TNM) Staging Criteria (Version 6)

Stage II is (T2,T3, N0, M0) tumor size more than 2 cm but no deep extradermal structure invasion, no regional lymph node metastasis, and no distant metastasis. Stage III is (T4, N0, M0) tumor invasion of deep extradermal structures, no regional lymph node metasis, and no distant metasasis or (Any T, N1, M0) Any tumor size, regional lymph node metastasis, and no distant metastasis. (NCT00861705)
Timeframe: at definitive surgery, up to 28 weeks

,,,
Interventionparticipants (Number)
Breast : Stage IIBreast : Stage IIIBreast/Axilla : Stage IIBreast/Axilla : Stage III
Arm 1 (Pac --> ddAC)42424136
Arm 2 (Pac + Bev --> ddAC + Bev)49554245
Arm 3 (Pac + Carboplatin --> ddAC)51574751
Arm 4 (Pac + Carboplatin + Bev --> ddAC + Bev)70626354

[back to top]

Number of Participants With Adverse Events (AEs) or Deaths

Data presented are the number of participants who experienced 1 or more AEs, serious AEs (SAEs), and AEs that lead to death during the study including the 30-day follow-up. A summary of SAEs and other non-serious AEs, regardless of causality is located in the Reported Adverse Events section of this report. (NCT00870870)
Timeframe: Randomization to last dose of study medication (up to 11.7 months) plus 30-day safety follow-up

,,,
InterventionParticipants (Count of Participants)
AEsSAEsDeaths Due to AEs
GCC Plus Cixutumumab651
GCiC Plus Cixutumumab25151
Gemcitabine/Carboplatin/Cetuximab (GCC)441
Gemcitabine/Cisplatin/Cetuximab (GCiC)29204

[back to top]

Time To Progression (TTP)

TTP was defined as the duration from the date of randomization until the date of disease progression. Response was defined using RECIST v 1.0 criteria. PD was defined as having a ≥20% increase in the sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants without disease progression, TTP was censored at the date of last objective tumor assessment. For participants without disease progression and were subsequently lost to follow-up, TTP was censored at the date of last follow-up visit or at the date of last contact. (NCT00870870)
Timeframe: Randomization to months until PD or censor (up to 16.9 months)

Interventionmonths (Median)
GCiC5.8
GCiC Plus Cixutumumab5.7

[back to top]

Progression-Free Survival (PFS)

PFS was defined as the duration from the date of randomization until disease progression or death due to any cause, whichever occurred first. Response was defined using RECIST, v 1.0 criteria. PD was defined as having a ≥20% increase in sum of LD of target lesions or the appearance of new lesions and/or unequivocal progression of non-target lesions. For participants who were alive and without disease progression, PFS was censored at the date of last objective tumor assessment. For participants who did not experience disease progression and were lost to follow-up, PFS was censored at the date of the last objective tumor assessment or the date of last contact. (NCT00870870)
Timeframe: Randomization to PD or death due to any cause or censor (up to 16.9 months)

Interventionmonths (Median)
GCiC4.2
GCiC Plus Cixutumumab5.6

[back to top]

Percentage of Participants With Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

ORR was defined as the percentage of participants achieving either CR or PR. Response was defined using Response Evaluation Criteria in Solid Tumors (RECIST), version (v) 1.0 criteria. CR was defined as the disappearance of all target and non-target lesions and the normalization of the tumour marker level. PR was defined as having at least a 30% decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Percentage of participants is calculated as a total number of participants with CR or PR / total number of participants treated * 100. (NCT00870870)
Timeframe: Randomization to measured progressive disease (PD) (up to 16.9 months)

Interventionpercentage of participants (Number)
Gemcitabine/Cisplatin/Cetuximab (GCiC)31.0
GCiC Plus Cixutumumab20.0

[back to top]

Overall Survival (OS)

OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive, OS was censored at the date of last follow-up visit or at the date of last contact. (NCT00870870)
Timeframe: Randomization to death due to any cause or censor (up to 30.4 months)

Interventionmonths (Median)
GCiC11.5
GCiC Plus Cixutumumab8.9

[back to top]

Duration of Response

The duration of CR or PR was defined as the time from first objective status assessment of CR or PR to the first time of disease progression or death. Response was defined using RECIST v 1.0 criteria. CR was defined as the disappearance of all target lesions and non-target lesions. PR was defined as having at least a 30% decrease in sum of LD of target lesions. Duration of response was censored on the date of last tumor assessment for participants who were alive and have no evidence of disease progression. (NCT00870870)
Timeframe: Date of first response to the date of PD or death due to any cause or censor ( up to 15.5 months)

Interventionmonths (Median)
GCiC4.8
GCiC Plus Cixutumumab4.8

[back to top]

Overall Survival (OS)

Time from the date of randomization to the date of death (NCT00873119)
Timeframe: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Interventionmonths (Median)
Arm A - BelCaP11.5
Arm B - CaP9.1

[back to top]

Progression Free Survival

Time from the date of randomization to the time of disease progression or death due to any cause, measured by RECIST criteria (Response Evaluation Criteria In Solid Tumors). (NCT00873119)
Timeframe: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Interventionmonths (Median)
Arm A - BelCaP5.4
Arm B - CaP5.3

[back to top]

Best Overall Response

The best overall response in an individual patient according to the RECIST criteria (Eisenhauer 2009 ) is the best response recorded from the start of the treatment until disease progression/recurrence. Objective response is defined as best overall response of complete response (CR) or partial response (PR) (NCT00873119)
Timeframe: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Interventionpercentage of participants (Number)
Arm A - BelCaP43.2
Arm B - CaP22.2

[back to top]

Duration of Response

Duration of overall response was measured from the time that measurement criteria were first met for CR or PR (whichever status was recorded first) until the first date that PD ([Progressive Disease]) or death was documented (NCT00873119)
Timeframe: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Interventionmonths (Median)
Arm A - BelCaP4.6
Arm B - CaP6.5

[back to top]

Time to Response

For patients with overall best response being CR or PR, time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR (whichever status is recorded first) were met (NCT00873119)
Timeframe: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Interventionmonths (Median)
Arm A - BelCaP3.2
Arm B - CaPNA

[back to top]

Time to Progression (TTP)

Time from the date of randomization to the time of disease progression (NCT00873119)
Timeframe: Tumor assessment every 6 weeks for the treatment period. Subsequent assessments every 6 weeks for the initial 6 months, then every 9 weeks for 6 months, then every 12 weeks for 12 months and then every 6 months until 5 years from the start of study

Interventionmonths (Median)
Arm A - BelCaP5.7
Arm B - CaP5.6

[back to top]

Duration of Time to Progression (TTP) in Each Study Arm Based on Independent Central Radiology Review

"Time-to-progression (TTP) was defined as the time from the date of randomization to the first date of documented progressive disease. Progressive disease was identified by radiologic progressive disease according to modified RECIST v1.0, or in the case of the Investigator Radiologic Review, it may also be defined by clinical progression as determined by the investigator.~If a subject received any further anti-cancer therapy without prior documentation of disease progression, the subject was censored at the date of last tumor assessment before starting anti-cancer treatment. Subjects who died on study from other causes (not related to study disease) and subjects who were lost to follow-up or who were alive without documented progressive disease as of the data cut-off date for analysis were censored at the last tumor assessment date." (NCT00874848)
Timeframe: From time of randomization to first date of documented progression, or last tumor assessment date, up to 15 months

Interventionmonths (Median)
Imprime PGG Arm6.4
Control Arm6.0

[back to top]

Disease Control Rate (DCR) in Each Study Arm Based on Independent Central Radiology Review

"The disease control rate (DCR) was defined as the number of participants experiencing a best overall tumor response of either CR, PR or SD. For stable disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.~The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines." (NCT00874848)
Timeframe: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months

Interventionparticipants (Number)
Imprime PGG Arm35
Control Arm21

[back to top]

Duration of Objective Tumor Response in Each Study Arm Based on Independent Central Radiology Review

"The duration of objective tumor response was measured from the time at which criteria are met for CR or PR (whichever status is recorded first) until the first date on which recurrence or progressive disease is objectively documented per modified RECIST v1.0. Subjects who did not progress as of the data cutoff date were censored at their last tumor assessment date.~The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines." (NCT00874848)
Timeframe: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months

Interventionmonths (Median)
Imprime PGG Arm4.4
Control Arm4.1

[back to top]

Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Rates in Each Study Arm Based on Independent Central Radiology Review

"The best observed overall response rates were defined as the number of participants experiencing a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) based on the modified RECIST v1.0 criteria. For stable disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.~The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines." (NCT00874848)
Timeframe: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months

,
Interventionparticipants (Number)
Number of participants with best response of CRNumber of participants with best response of PRNumber of participants with best response of SD
Control Arm0615
Imprime PGG Arm01520

[back to top]

Overall Survival (OS) in Each Study Arm Based on the Safety Population

Overall survival (OS) was defined as the time from the date of randomization until the date of documented death of the subject due to any cause, including death due to relapses that were successfully retreated. Subjects who were lost to follow-up or who were still alive at the time of analysis were censored at the last contact dates. (NCT00874848)
Timeframe: From the time of randomization to death, subject being lost to follow-up or study completion

Interventionmonths (Median)
Imprime PGG Arm10.3
Control Arm12.4

[back to top]

Objective Response Rate (ORR) in Each Study Arm Based on Independent Central Radiology Review

"Overall objective response rate was defined as the number of participants experiencing a best overall response of either complete response (CR) or partial response (PR) based on the modified RECIST v1.0 criteria.~The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines." (NCT00874848)
Timeframe: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months

,
Interventionparticipants (Number)
Number of participants with best response of CRNumber of participants with best response of PR
Control Arm06
Imprime PGG Arm015

[back to top]

Number of Subjects Experiencing Adverse Events

The number of subjects experiencing adverse events after receiving protocol therapy. (NCT00875615)
Timeframe: 36 months

Interventionparticipants (Number)
Cisplatin or Carboplatin + Sorafenib2

[back to top]

Number of Patients Achieving Clinical Benefit

Number of patients achieving complete or partial response according to RECIST criteria (NCT00875615)
Timeframe: 36 months

Interventionparticipants (Number)
Cisplatin or Carboplatin + Sorafenib6

[back to top]

Median Progression Free Survival of This Treatment Regimen in Patients With Advanced/Recurrent Endometrial Cancer.

Median progression free survival measured in months. Progression of disease is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST version 1.0), as a 20% increased in the sum of the longest diameter of the target lesions, or a measurable increased in a non-target lesion, or the appearance of a new lesion. (NCT00879359)
Timeframe: 58 months

Interventionmonths (Median)
Maintenance Therapy With Bevacizumab18

[back to top]

Number of Participants With Adverse Events Grades 1-5

Toxicity and safety was monitored before every treatment cycle, during, and after treatment. Bevacizumab was discontinued if the following criteria was met: grade 4 hypertension, reversible posterior leukoencephalopathy syndrome or hypertensive encephalopathy, grade 4 nephritic syndrome, arterial thrombosis, symptomatic grade 4 or recurrent/worsening venous thromboembolic events after resumption of bevacizumab treatment, grade 3 hemorrhage, bowel perforation or fistula and any complete wound disruption. (NCT00879359)
Timeframe: 58 months

Interventionparticipants (Number)
Bowel PerforationLeukopenia (AE grade 1-5)Neutropenia (AE Grade 1-5)Thrombocytopenia (AE Grade 1-5)Anemia (AE Grade 1-5)Allergy/Immunology (AE Grades 1-5)Alopecia (AE Grades 1-5)Anorexia (AE Grades 1-5)Cough (AE Grades 1-5)Depression (AE Grades 1-5)Diarrhea (AE Grades 1-5)Dyspnea (AE Grades 1-5)Epistaxis (AE Grades 1-5)Fatigue (AE Grades 1-5)Gastrointestinal (AE Grades 1-5)Hemorrhage (AE Grades 1-5)Hoarseness (AE Grades 1-5)Hypercalcemia (AE Grades 1-5)Infection (AE Grades 1-5)Lymphatics (AE Grades 1-5)Nausea (AE Grades 1-5)Neurosensory (AE Grades 1-5)Ocular/Visual (AE Grades 1-5)Pain (AE Grades 1-5)Rash (AE Grades 1-5)Rhinitis (AE Grades 1-5)TinitusVomiting (AE Grades 1-5)
Maintenance Therapy With Bevacizumab113129152108425311291212166153113

[back to top]

Febrile Neutropenia

The primary endpoint of the study was safety, as reflected by a febrile neutropenia rate of <10%. (NCT00883675)
Timeframe: 2 months

Interventionparticipants (Number)
Treatment12

[back to top]

Time to Deterioration in TOI Using FACT-L Version 4.0

"Time to deterioration in TOI is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in TOI or death on study. TOI is defined as the sum of the scores of the PWB, FWB, and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = not at all and 4 = very much. The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 84; higher score indicates better physical aspects of QoL. A clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. Participants without deterioration in TOI at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method." (NCT00883779)
Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Interventionmonths (Median)
Placebo5.6
Erlotinib6.3

[back to top]

Time to Progression

Time to progression is defined as the time between the date of randomization and the date of the first documented disease progression. Participants who have not progressed at the time of study completion (or data cut off) or who were lost to follow up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow-up for progression of disease, whichever was latest. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Participants with no post baseline tumor assessments were censored at the time of randomization. Analysis was performed using Kaplan-Meier method. (NCT00883779)
Timeframe: Randomization until PD (assessed at baseline and every 8 weeks thereafter until PD or end of study [up to approximately 1.5 years])

Interventionmonths (Median)
Placebo6.5
Erlotinib7.9

[back to top]

Time to Symptomatic Progression

"Time to symptomatic progression was the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. LCS scores were obtained from a 7-item questionnaire from the FACT-L (version 4.0). Participants responded to questions such as shortness of breath, cough, tightness in chest, breathing difficulty, appetite loss, weight loss and unclear thinking; on a 5-point scale from 0-4, where 0 = not at all and 4 = very much. The participants' responses were summed to result in an overall score, scores range on a scale of 0 (most symptomatic) to 28 (asymptomatic); higher score indicates fewer symptoms. A clinically meaningful decline used to determine symptomatic progression in this study was at least a three point decline in LCS score from baseline. Participants without symptomatic progression at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method." (NCT00883779)
Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Interventionmonths (Mean)
Placebo6.6
Erlotinib7.2

[back to top]

Median Overall Survival (OS) Time-Overall and Among Different Subgroups

OS was defined as the time between the date of randomization and the date of death from any cause. Participants for whom no death was captured on the clinical database were censored at the most recent date they were known to be alive. Participants with no post baseline information were censored at the time of randomization. OS among different subgroups of type of carcinoma, smoking habit, EGFR mutation type, KRAS mutation type, EGFR IHC test result type, and EGFR FISH result type. Analysis was performed using Kaplan-Meier method. (NCT00883779)
Timeframe: Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years])

,
Interventionmonths (Median)
Overall participants (n=225,226)Adenocarcinoma (n=168,174)Non-adenocarcinoma (n=57,52)Never smoked (n=107,112)Current/former smoker (n=118,114)EGFR mutation (n=48,49)EGFR wild-type (n=67,69)KRAS mutation (n=11,10)KRAS wild-type (n=101,101)EGFR IHC positive (n=36,40)EGFR IHC negative (n=25,12)EGFR FISH positive (n=20,14)EGFR FISH negative (n=23,25)
Erlotinib18.220.910.325.913.030.314.917.518.118.621.943.116.7
Placebo15.215.812.417.513.020.612.211.214.115.212.517.712.5

[back to top]

Median PFS Time Based on Different Subgroups

Tumor response was evaluated according to RECIST (version 1.0). PD was defined in outcome measure 1. PFS is the time (in months) between the date of randomization and the date of first documented disease progression or death from any cause, whichever comes first. Participants who had neither progressed nor died at the time of data cut-off or who were lost to follow-up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow up for progression of disease, whichever was last. Participants without post baseline tumor assessments who were known to be alive were censored at the time of randomization. PFS among different subgroups of type of carcinoma, smoking habit, epidermal growth factor receptor (EGFR) mutation type, KRAS mutation type, EGFR immunohistochemistry (IHC) test result type, and EGFR fluorescent in situ hybridization (FISH) result type. (NCT00883779)
Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

,
Interventionmonths (Median)
Adenocarcinoma (n=168,174)Non-adenocarcinoma (n=57,52)Never smoked (n=107,112)Former/current smoker (n=118,114)EGFR mutation (n=48,49)EGFR wild-type (n=67,69)KRAS mutation (n=11,10)KRAS wild-type (n=101,101)EGFR IHC positive (n=36,40)EGFR IHC negative (n=25,12)EGFR FISH positive (n=20,14)EGFR FISH negative (n=23,25)
Erlotinib8.25.710.95.715.67.16.08.08.110.112.97.5
Placebo6.55.86.65.96.95.94.56.86.06.75.96.0

[back to top]

Percentage of Participants Alive at the End of Study-Overall and Among Different Subgroups

(NCT00883779)
Timeframe: Randomization until death (assessed at baseline and every 8 weeks thereafter until death or end of study [up to approximately 5.5 years])

,
Interventionpercentage of participants (Number)
Overall participants (n=225,226)Adenocarcinoma (n=168,174)Non-adenocarcinoma (n=57,52)Never smoked (n=107,112)Current/former smoker (n=118,114)EGFR mutation (n=48,49)EGFR wild-type (n=67,69)KRAS mutation (n=11,10)KRAS wild-type (n=101,101)EGFR IHC positive (n=36,40)EGFR IHC negative (n=25,12)EGFR FISH positive (n=20,14)EGFR FISH negative (n=23,25)
Erlotinib15.919.53.823.28.830.610.120.017.825.033.342.916.0
Placebo13.314.98.813.113.622.97.50.014.911.18.010.013.0

[back to top]

Percentage of Participants With Symptomatic Progression Assessed Using the Lung Cancer Subscale (LCS)

"LCS scores were obtained from a 7-item questionnaire from the Functional Assessment of Cancer Therapy - Lung (FACT-L) (version 4.0). Participants responded to questions such as shortness of breath, cough, tightness in chest, breathing difficulty, appetite loss, weight loss and unclear thinking; on a 5-point scale from 0-4, where 0 equaled (=) not at all and 4 = very much. The participants' responses were summed to result in an overall score, scores range on a scale of 0 (most symptomatic) to 28 (asymptomatic); higher score indicates fewer symptoms. A clinically meaningful decline used to determine symptomatic progression in this study was at least a three point decline in LCS score from baseline. Participants without symptomatic progression at the time of analysis were censored at the time of the last FACT-L assessment." (NCT00883779)
Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Interventionpercentage of participants (Number)
Placebo72.4
Erlotinib66.4

[back to top]

Duration of Response

Duration of response is defined as the time between the date of first documented response (CR or PR, as determined by the RECIST criteria) and the date of first documented PD or death. Participants who did not progress or die after they had a confirmed response (CR or PR) were censored at the date of their last tumor assessment where non-progression was documented or last date of follow-up for progression of disease, whichever was last. CR and PR are defined in Outcome Measure 7. (NCT00883779)
Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Interventionmonths (Median)
Placebo5.6
Erlotinib10.3

[back to top]

Median Follow-up Time During the Study

Median follow-up was calculated using 'Reverse Kaplan-Meier' analysis for Overall survival. (NCT00883779)
Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 5.5 years])

Interventionmonths (Median)
Placebo50.3
Erlotinib50.2

[back to top]

Median Progression Free Survival (PFS) Time

Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). PD was defined as at least a 20 percent (%) increase in the sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. PFS is the time (in months) between the date of randomization and the date of first documented disease progression or death from any cause, whichever comes first. Participants who had neither progressed nor died at the time of data cut-off or who were lost to follow-up were censored at the date of the last tumor assessment where non-progression was documented or last date of follow up for progression of disease, whichever was last. Participants without post baseline tumor assessments who were known to be alive were censored at the time of randomization. Analysis was performed using Kaplan-Meier method. (NCT00883779)
Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Interventionmonths (Median)
Placebo6.0
Erlotinib7.6

[back to top]

Non-Progression Rate: Percentage of Participants With a Confirmed Best Overall Response of Either Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for At Least 16 Weeks

Tumor response was evaluated according to RECIST (version 1.0). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the screening sum LD; SD for target lesions is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and SD for non-target lesions defined as persistence of 1 or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. Responses were confirmed with repeated assessment 4 weeks after initial response was observed. (NCT00883779)
Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Interventionpercentage of participants (Number)
Placebo64.4
Erlotinib67.3

[back to top]

Objective Response Rate: Percentage of Participants With a Confirmed Best Overall Response of CR or PR

Tumor response was evaluated according to RECIST (version 1.0). CR is defined as the disappearance of all target and non-target lesions and normalization of tumor marker level; PR is defined as at least a 30% decrease in the sum of the LD of target lesions, taking as reference the screening sum LD. Responses were confirmed with repeated assessment 4 weeks after initial response was observed. (NCT00883779)
Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Interventionpercentage of participants (Number)
Placebo17.8
Erlotinib42.9

[back to top]

Percentage of Participants Alive and Free From Disease Progression

Tumor response was evaluated according to RECIST (version 1.0). PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. (NCT00883779)
Timeframe: Randomization until PD or death (assessed at baseline and every 8 weeks thereafter until PD, death or end of study [up to approximately 1.5 years])

Interventionpercentage of participants (Number)
Placebo6.2
Erlotinib22.6

[back to top]

Percentage of Participants With Deterioration in Quality of Life (QOL) Using FACT-L Version 4.0

"Total FACT-L score was defined as the sum of the TOI, Social Well Being (SWB) and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = not at all and 4 = very much. The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 136; higher score indicates better QoL. A clinically meaningful decline used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment." (NCT00883779)
Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Interventionpercentage of participants (Number)
Placebo79.6
Erlotinib70.4

[back to top]

Percentage of Participants With Deterioration in Trial Outcome Index (TOI) Using FACT-L Version 4.0

"TOI was defined as the sum of the scores of the Physical Well-Being (PWB), Functional Well-Being (FWB), and LCS. PWB, FWB, and LCS scores were obtained from 7-item questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = not at all and 4 = very much. The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 84; higher score indicates better physical aspects of quality of life (QoL). A clinically meaningful decline used to determine deterioration in TOI was greater than or equal to (≥) 6-point decline from baseline. Participants without deterioration in TOI at the time of analysis were censored at the time of the last FACT-L assessment." (NCT00883779)
Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Interventionpercentage of participants (Number)
Placebo75.6
Erlotinib65.9

[back to top]

Time to Deterioration in QOL Using FACT-L Version 4.0

"Time to deterioration in QoL is defined as time from randomization until the earlier of a clinically meaningful decline from baseline in Total FACT-L or death on study. Total FACT-L score was defined as the sum of the TOI, SWB and EWB of the FACT-L questionnaires. TOI (PWB + FWB + LCS), SWB and EWB scores were obtained from 7-item (6-item in the case of EWB) questionnaires from the FACT-L (Version 4.0). Participants responded to questions on a 5-point scale from 0-4, where 0 = not at all and 4 = very much. The participants' responses were summed to result in an overall score, scores range on a scale of 0 to 136; higher score indicates better QoL. A clinically meaningful decline used to determine deterioration in QoL was ≥6-point decline from baseline. Participants without deterioration in QoL at the time of analysis were censored at the time of the last FACT-L assessment. Analysis was performed using Kaplan-Meier method." (NCT00883779)
Timeframe: Baseline, Day 1 of Cycles 3 and 5, Day 1 of post-study Visits 1 and 2 until end of study medication administration or PD (up to approximately 1.5 years)

Interventionmonths (Median)
Placebo4.5
Erlotinib5.6

[back to top]

Number of Participants With Adverse Events as a Measure of Safety and Tolerability

Assessments will be made through analysis of reported incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs) at the phase II dose (NCT00887575)
Timeframe: Days 1, 8, and 15 of each 4-week cycle up to 24 weeks during neoadjuvant treatment, and every 4 weeks during maintenance treatment

Interventionparticipants (Number)
NeutropeniaAnemiaThrombocytopeniaLeukopeniaFebrile neutropeniaFatigueAlopeciaNausea/VomitingConstipationDiarrheaMucositisDysgeusiaPeripheral neuropathyDyspepsiaDyspneaAnorexiaFeverBleedingInsomniaPain in extremitySkin toxicity
Phase II- Sunitinib/Paclitaxel/Carboplatin343030303322624222117171713121099999

[back to top]

Overall Survival (OS)

Defined as the time between Day 1 Cycle 1 to time of death from any cause. (NCT00887575)
Timeframe: 24 months

Interventionprobability of overall survival at 24 m (Number)
Dose Level I0.8912

[back to top]

Overall Response Rate (ORR)

Assessed by clinical, radiologic and surgical determinations before and after neoadjuvant therapy. Measurable lesions will be defined by RECIST criteria v1.1. (NCT00887575)
Timeframe: Days 1, 8 and 15 of each cycle, minimum of 12 weeks

Interventionparticipants (Number)
Phase II- Sunitinib/Paclitaxel/Carboplatin25

[back to top]

Phase II: The Number of Subjects Exhibiting Pathologic Complete Response to Neoadjuvant Treatment With Sunitinib/Paclitaxel/Carboplatin

Pathologic complete response (PCR) is defined as no residual invasive breast cancer in final breast or axillary lymph node samples. (NCT00887575)
Timeframe: at weeks 26-30

Interventionparticipants (Number)
Phase II- Sunitinib/Paclitaxel/Carboplatin12

[back to top]

Disease-free Survival

Defined as the time between day of surgery to first documented disease occurrence or death due to any cause. (NCT00887575)
Timeframe: every 4 weeks from date of surgery until treatment discontinuation or death, expected average 18 months

Interventionmonths (Median)
Median Overall SurvivalMedian Disease-Free Survival
Dose Level INA15.8357

[back to top]

Overall Survival (OS)

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death (NCT00892710)
Timeframe: 18 months

Interventionmonths (Median)
Pemetrexed7.7
Pemetrexed/Bevacizumab8.6
Pemetrexed/Bevacizumab/Carboplatin8.7

[back to top]

Overall Response Rate (ORR), the Number of Patients Who Experience an Objective Benefit From Treatment

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00892710)
Timeframe: 18 months

Interventionparticipants (Number)
Pemetrexed7
Pemetrexed/Bevacizumab18
Pemetrexed/Bevacizumab/Carboplatin24

[back to top]

Progression Free Survival (PFS)

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00892710)
Timeframe: 18 months

Interventionmonths (Median)
Pemetrexed2.8
Pemetrexed/Bevacizumab4.0
Pemetrexed/Bevacizumab/Carboplatin4.8

[back to top]

Time to Progression (TTP)

The Length of Time, in Months, That Patients Remain Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00892710)
Timeframe: 18 months

Interventionmonths (Median)
Pemetrexed3.5
Pemetrexed/Bevacizumab5.3
Pemetrexed/Bevacizumab/Carboplatin5.7

[back to top]

Time to Treatment Failure (TTTF)

Defined as the Length of Time, in Months, that Patients were Alive from the Date of First Treatment Until Treatment Discontinuation for Any Reason. (NCT00892710)
Timeframe: 18 months

Interventionmonths (Median)
Pemetrexed2.4
Pemetrexed/Bevacizumab3.1
Pemetrexed/Bevacizumab/Carboplatin3.3

[back to top]

6-month and 12-month Overall Survival Probability

Overall Survival = The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death (NCT00892710)
Timeframe: 12 months

,,
Interventionprobability out of 1 (Number)
6-month OS probability12-month OS probability
Pemetrexed0.520.3
Pemetrexed/Bevacizumab0.610.32
Pemetrexed/Bevacizumab/Carboplatin0.570.44

[back to top]

Objective Response Rate and Clinical Benefit Rate

Estimated as the proportion of subjects who meet the criteria for complete or partial response (CR or PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 - for target lesions assessed by MRI: Complete Response (CR) is defined as disappearance of all target lesions; Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions. (NCT00894504)
Timeframe: every 6 weeks until treatment discontinuation

InterventionParticipants (Number)
Clinical benefit rate (CR + PR + SD>6 months)Objective response rate (CR + PR)
Panitumumab/Gemcitabine/Carboplatin3230

[back to top]

Correlation of Biomarker Expressions of EGFR, K-ras, p53, PTEN Expression, and PI3K in Triple-negative Breast Cancer With Response to Treatment With the Combination of Gemcitabine, Carboplatin, and Panitumumab

Median PFS (95% CI), months, reported by biomarker expression/mutation status for: EGFR, p53, PTEN, PIK3CA, KRAS (NCT00894504)
Timeframe: 18 months

Interventionmonths (Median)
EGFR Normal4.57
EGFR Amplified3.42
p53 Normal4.16
p53 Loss5.32
PTEN Normal4.4
PTEN Loss2.91
PIK3CA No Mutation4.37
PIK3CA Mutation(s)4.73

[back to top]

Progression-free Survival (PFS)

Measured from Day 1 of study drug administration to disease progression - defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as a 20% increase in the sum of the longest diameter of target lesions and/or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions (NCT00894504)
Timeframe: every 6 weeks until treatment discontinuation

InterventionMonths (Median)
Panitumumab/Gemcitabine/Carboplatin4.4

[back to top] [back to top]

Number of Participants With Treatment Response

"Participants who completed 1 cycle of docetaxel, cisplatin, and 5-fluorouracil (TPF) were evaluated for response. Response was assessed for lesions designated as target (TL) and non-target (NTL) as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). The outcome is reported as a number without dispersion.~TL Criterion:~CR: Disappearance of lesions~PR: 30% decrease in the sum of the longest diameter (LD) of lesions~PD: 20% increase in the sum of the LD of lesions, or any new lesion~SD: Neither sufficient shrinkage for PR nor sufficient increase for PD~NTL Criterion:~CR: Disappearance of lesions and normalization of tumor marker level~PR / SD: Persistence of one or more lesion(s) and/or maintenance of tumor marker level above the normal limits (includes incomplete response / PR).~PD: Appearance of one or more new lesions and/or unequivocal progression of existing lesions." (NCT00896181)
Timeframe: up to 29 months (ie, 24 months post-chemoradiation)

InterventionParticipants (Count of Participants)
CR for M0 (non-metastatic lesion)PR for M0 (non-metastatic lesion)SD for M0 (non-metastatic lesion)PD for M0 (non-metastatic lesion)CR for M1 (metastatic lesion)PR for M1 (metastatic lesion)SD for M1 (metastatic lesion)PD for M1 (metastatic lesion)
Chemoradiation for Nasopharyngeal Carcinoma173003100

[back to top]

Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy

Progression-free survival (PFS) means to remain alive without disease progression. Progression is defined as either the appearance of one or more new cancer lesions, or a ≥ 20% increase in the sum of the longest diameters (LD) of target cancer lesions, compared the same measurement obtained at the start of treatment. This outcome reported as the number of patients remaining alive at 2 years following chemo-radiotherapy without disease progression, a number without dispersion. (NCT00896181)
Timeframe: up to 29 months (ie, 24 months post-chemoradiation)

InterventionParticipants (Count of Participants)
M0 (non-metastatic lesion)M1 (metastatic lesion)
Chemoradiation for Nasopharyngeal Carcinoma184

[back to top]

Median Progression-free Survival (PFS)

Progression-free survival (PFS) means to remain alive without disease progression. Progression is defined as either the appearance of one or more new cancer lesions, or a ≥ 20% increase in the sum of the longest diameters (LD) of target cancer lesions, compared the same measurement obtained at the start of treatment. This outcome reported as the median duration of PFS in months since chemo-radiotherapy, with full range. (NCT00896181)
Timeframe: up to 127 months (includes treatment period of up to 5 months)

Interventionmonths (Median)
M0 (non-metastatic lesion)M1 (metastatic lesion)
Chemoradiation for Nasopharyngeal Carcinoma7633

[back to top]

Number of Participants With Adverse Events Resulting in Treatment Discontinuation

Adverse events during treatment were assessed as whether they were definitely-, probably-, or possibly-related to protocol treatment (ie, adverse reaction). The outcome is reported as the number of participants who discontinued treatment due to an adverse reaction. (NCT00896181)
Timeframe: 8 months

InterventionParticipants (Count of Participants)
Chemoradiation for Nasopharyngeal Carcinoma1

[back to top]

Overall Survival (OS)

Overall survival (OS) was assessed as the duration of time that study participants remained alive after chemoradiotherapy. The outcome is reported as median OS (with full range). (NCT00896181)
Timeframe: up to 127 months (includes treatment period of up to 5 months)

Interventionmonths (Median)
M0 (non-metastatic lesion)M1 (metastatic lesion)
Chemoradiation for Nasopharyngeal Carcinoma7976

[back to top]

3-Year Overall Survival Rate

The percentage of patients who were alive at 3 years from time of first study treatment until date of death from any cause. Overall survival is shown for the Intent-to-Treat population. (NCT00906282)
Timeframe: 36 months

Interventionpercentage of participants (Number)
Pemetrexed/Carboplatin/Surgery45

[back to top]

Rate of Residual Disease as an Assessment of Pathological Partial Response (pPR)

pPR was further assessed by the amount of residual tumor measured at surgery: microscopic residual disease = less than 1 centimeter (<1 cm); macroscopic residual disease = 1 centimeter or greater (≥1 cm). (NCT00906282)
Timeframe: At 15-18 weeks

Interventioncentimeters (Median)
Pemetrexed/Carboplatin/Surgery2.5

[back to top]

Objective Tumor Response

Objective Tumor Response defined as the percent of patients who completed up to 4 cycles of pre-operative chemotherapy and achieved a complete response (CR) or partial response (PR) assessed by Response Evaluation in Solid Tumors (RECIST) 1.0. Patients with stable disease (SD) or response to treatment were deemed surgical candidates. [CR=disappearance of all target tumors; PR= ≥30% decrease in the sum of the longest diameters of target tumors. SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.] (NCT00906282)
Timeframe: At 6 and 12 weeks

Interventionpercentage of participants (Number)
PRSD
Pemetrexed/Carboplatin/Surgery4148

[back to top]

Pathologic Response Rate

Percent of patients having a pathological complete or partial response (pCR or pPR) at surgery. pCR defined as complete removal of all tumor. pPR defined as residual viable tumor demonstrated in the resected specimen. (NCT00906282)
Timeframe: weeks 15 -18

Interventionpercentage of participants (Number)
pPRpCR
Pemetrexed/Carboplatin/Surgery1000

[back to top]

Complete Resection Rate

The percent of patients who had surgical resection listed by procedure type: lobectomy or pneumonectomy, or resection of adjacent chest wall or mediastinal structures when appropriate. Surgery followed standard guidelines for resection of non-small-cell lung cancer (NSCLC). (NCT00906282)
Timeframe: At weeks 15-18

Interventionpercentage of patients (Number)
LobectomyWedge ResectionPneumonectomyBilobectomy
Pemetrexed/Carboplatin/Surgery7015114

[back to top]

Vorinostat Maximum Tolerated Dose (MTD) [Phase Ib]

The Vorinostat MTD is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed, the MTD is not reached. (NCT00910000)
Timeframe: The DLT observation period in determining the MTD was the 21-day cycle 1 length.

Interventionmg/day (Number)
All Phase Ib ParticipantsNA

[back to top]

Response

Response was based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. Progressive disease (PD) is at least a 20% increase in sum LD from the smallest LD recorded on treatment. Stable disease (SD) is neither sufficient increase to qualify as PD nor sufficient shrinkage to qualify for PR. For CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed 4 weeks +/- 2 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Participants who received therapy but did not have their disease re-evaluated were considered unevaluable. (NCT00910000)
Timeframe: Disease was assessed radiographically (CT or MRI scan) every 2 cycles on treatment; Phase Ib participants received up to 8 cycles of treatment. The median number of cycles started was 2 (range 1-8).

,,,,,
Interventionparticipants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseUnevaluable
Dose Level 1A03000
Dose Level 1B00003
Dose Level 1C01001
Dose Level 1D02001
Dose Level 2A00102
Dose Level 2D00001

[back to top]

Dose Limiting Toxicity (DLT) [Phase Ib]

"Dose-limiting toxicity was based on the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) and defined as any of the following:~Any CTCAE grade 3 or 4 non-hematologic event except manageable gastrointestinal toxicity and fatigue.~Any of the following hematologic events (excluding neutropenia lasting < 5 days):~i) febrile neutropenia defined as grade 3-4 neutropenia with fever ≥ 38.5°C and/or infection.~ii) any grade 4 neutropenia lasting 5 days or more. iii) grade 4 thrombocytopenia (plt count < 25x 109/L) iv) failure of ANC to recover to ≥ 1000/μL or platelets to recover to ≥ 50,000/μL within 14 days of therapy v) grade 4 anemia~Any clinically significant abnormal laboratory value that results in dose delay of >14 days.~<75% of vorinostat dosing taken by the patient during the first cycle due to any toxicity." (NCT00910000)
Timeframe: The DLT observation period in determining the MTD was the 21-day cycle 1 length.

Interventionparticipants with DLT (Number)
Dose Level 1A0
Dose Level 2A2
Dose Level 1B2
Dose Level 1C2
Dose Level 1D0
Dose Level 2D1

[back to top] [back to top]

The Incidence and Time to Development of Local Failure (LF)

"The Primary Objective is assess and compare the incidence and time to development of local failure, among IMRT-Group 1 or PSPT-Group 2 using Bayesian randomization. Local failure was defined as treatment failure within the planning target volume plus a # 1-cm margin. Images used to report Local failure were registered with radiation dose distribution to accurately assess the location of the failure. Biopsy to confirm Local failure was strongly recommended (Data Supplement). An internal outcomes review committee reviewed each event to ensure objectivity and consistency in reporting Local failure. Final RP outcomes also were reviewed and approved by independent external experts.~Tumor recurrence after achieving complete response,~Residual tumor enlargement of 20% or more on CT according to RECIST criteria,~Recurrence of PET FDG Avidity after achieving complete metabolic response,~Increase in FDG avidity in residual tumor,~Pathologically proven recurrence" (NCT00915005)
Timeframe: From date of protocol registration until the date of first documented development of CTCAE v3.0 grade > 3 TRP or local failure, whichever occurs first, in both treatment groups, assessed up to 6 years.

,
Interventionparticipants (Number)
Local FailureLocal Failure at 12 months
Intensity-modulated (Photon) Radiotherapy (IMRT)1810
Passive Scattering Proton Therapy (PSPT)146

[back to top]

Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. (NCT00918203)
Timeframe: Baseline to Study Completion (Up to 43 Months)

,,
Interventionparticipants (Number)
AESAE's
Crossover to Olaratumab102
Olaratumab + Pacilitaxel + Carboplatin6630
Paclitaxel + Carboplatin6321

[back to top]

PK - Maximum Concentration (Cmax) of Olaratumab

(NCT00918203)
Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose

Interventionmicrograms/milliliter (ug/mL) (Geometric Mean)
Olaratumab + Paclitaxel + Carboplatin489

[back to top]

PK - Half-Life (t1/2) of Olaratumab

(NCT00918203)
Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose

Interventiondays (Geometric Mean)
Olaratumab + Paclitaxel + Carboplatin5.79

[back to top]

PK - Clearance (Cl) of Olaratumab

(NCT00918203)
Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hr, 24,48,96,168 Hrs Post Dose

InterventionLiter/hour (L/h) (Geometric Mean)
Olaratumab + Paclitaxel + Carboplatin0.0218

[back to top]

Pharmacokinetics (PK) - Area Under the Curve (AUC) 0-168 of Olaratumab

AUC(0-168) = area under the concentration versus time curve from time zero to 168 hours post dose. (NCT00918203)
Timeframe: Cycle 3, Day 1: Predose, 30 minutes (min), 1.5 hours (hrs), 24,48,96,168 Hrs Post Dose

Interventionmicrogram*hour/milliliter (ug*hr/mL) (Geometric Mean)
Olaratumab + Paclitaxel + Carboplatin47600

[back to top]

Percentage of Participants With Anti-Olaratumab Antibodies

Participants with Treatment Emergent (TE) anti-olaratumab antibodies were participants with a 4-fold increase (2 dilutions) increase over a positive baseline antibody titer or for a negative baseline titer, a participant with an increase from the baseline to a level of 1:20. (NCT00918203)
Timeframe: Baseline to Study Completion (Up to 8 Months)

Interventionpercentage of participants (Number)
Olaratumab + Paclitaxel + Carboplatin4.4
Crossover to Olaratumab0.0

[back to top]

Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) Objective Tumor Response Rate (ORR)

The ORR is equal to the percentage of participants achieving a best overall response of partial response or complete response (PR + CR), according to RECIST version 1.1 criteria. CR was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as having at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase above nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100. (NCT00918203)
Timeframe: Baseline to Measured PD or Study Discontinuation (Up to 31 Months)

Interventionpercentage of participants (Number)
Olaratumab + Paclitaxel + Carboplatin41.8
Paclitaxel + Carboplatin34.4
Crossover to Olaratumab0

[back to top]

Overall Survival (OS)

Overall survival is defined as the time from date of randomization to the date of death from any cause. If the participant is alive at the end of the follow-up period or is lost to follow-up, OS was censored on the last date the participants is known to be alive. (NCT00918203)
Timeframe: Baseline to Death From Any Cause (Up to 31 Months)

Interventionweeks (Median)
Olaratumab + Paclitaxel + Carboplatin51.3
Paclitaxel + Carboplatin50.1

[back to top]

Median Duration of Response

The duration of overall response is measured from the time measurement criteria are first met for Complete Response (CR)/Partial Response (PR) (whichever is first recorded) until the first date that the criteria for PD are met (taking as a reference for PD the smallest measurement recorded since the treatment started), initiation of other/additional antitumor therapy is first reported, or death, is objectively documented. (NCT00918203)
Timeframe: First Criteria Met for CR or PR to Measured PD Start of Other Antitumor Therapy or Death From Any Cause (Up to 31 Months)

Interventionweeks (Median)
Olaratumab + Paclitaxel + Carboplatin14.4
Paclitaxel + Carboplatin12.9

[back to top] [back to top]

Progression-Free Survival (PFS)

PFS is defined as the time from the day of randomization to the first evidence of progression by RECIST version 1.1, or death from any cause. Participants who died without a reported prior progression were considered to have progressed on the day of their death. Participants who did not progress and were subsequently lost to follow-up had their data censored at the day of their last tumor assessment. If there was no radiologic assessment at baseline or post baseline, participants were censored at the date of randomization. If death or progressive disease (PD) occurred after 2 or more consecutive missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits. (NCT00918203)
Timeframe: Baseline to Measured PD or Death From Any Cause (Up to 31 Months)

Interventionweeks (Median)
Olaratumab + Paclitaxel + Carboplatin19.1
Paclitaxel + Carboplatin19.0
Crossover to Olaratumab8.3

[back to top]

PK - Steady State Volume of Distribution (Vss) of Olaratumab

(NCT00918203)
Timeframe: Cycle 3, Day 1: Predose, 30 min, 1.5 hrs, 24,48,96,168 Hrs Post Dose

InterventionLiter (L) (Geometric Mean)
Olaratumab + Paclitaxel + Carboplatin4.22

[back to top]

Baseline-adjusted QTcF, QTcB, PR Interval, and QRS Duration

"For each postbaseline timepoint, a participant's corresponding baseline measure was subtracted from his or her average of the triplicate ECG measure to create a baseline-adjusted corresponding ECG measure for each participant at each postbaseline timepoint." (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionmsec (Mean)
QTcF: Cycle 1 Day 2 (30 minutes postdose) (n=49)QTcF: Cycle 1 Day 8 (15 minutes predose) (n=50)QTcF: Cycle 1 Day 8 (30 minutes postdose) (n=50)QTcF: Cycle 2 Day 1 (15 minutes predose) (n=48)QTcF: Cycle 2 Day 1 (30 minutes postdose) (n=48)QTcB: Cycle 1 Day 2 (30 minutes postdose) (n=49)QTcB: Cycle 1 Day 8 (15 minutes predose) (n=50)QTcB: Cycle 1 Day 8 (30 minutes postdose) (n=50)QTcB: Cycle 2 Day 1 (15 minutes predose) (n=48)QTcB: Cycle 2 Day 1 (30 minutes postdose) (n=48)PR: Cycle 1 Day 2 (30 minutes postdose) (n=49)PR: Cycle 1 Day 8 (15 minutes predose) (n=50)PR: Cycle 1 Day 8 (30 minutes postdose) (n=50)PR: Cycle 2 Day 1 (15 minutes predose) (n=48)PR: Cycle 2 Day 1 (30 minutes postdose) (n=48)QRS: Cycle 1 Day 2 (30 minutes postdose) (n=49)QRS: Cycle 1 Day 8 (15 minutes predose) (n=50)QRS: Cycle 1 Day 8 (30 minutes postdose) (n=50)QRS: Cycle 2 Day 1 (15 minutes predose) (n=48)QRS: Cycle 2 Day 1 (30 minutes postdose) (n=48)
Trastuzumab + Docetaxel + Carboplatin3.5-9.3-4.3-15.6-13.43.9-0.81.4-13.2-14.2-0.11.44.29.713.7-0.1-1.8-1.8-0.5-0.3

[back to top]

Baseline-adjusted Heart Rate

"For each postbaseline timepoint, a participant's corresponding baseline heart rate was subtracted from his or her average of the triplicate heart rate to create a baseline-adjusted corresponding heart rate for each participant at each postbaseline timepoint." (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionbeats per minute (bpm) (Mean)
Cycle 1 Day 2 (30 minutes postdose) (n=49)Cycle 1 Day 8 (15 minutes predose) (n=50)Cycle 1 Day 8 (30 minutes postdose) (n=50)Cycle 2 Day 1 (15 minutes predose) (n=48)Cycle 2 Day 1 (30 minutes postdose) (n=48)
Trastuzumab + Docetaxel + Carboplatin0.59.66.23.1-0.7

[back to top]

Area Under the Curve From Time Zero to 6 Hours Post Infusion (AUC0-6hr) of Carboplatin

AUC0-6hr = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion. (NCT00927589)
Timeframe: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)

InterventionHour*microgram/milliliter (hr*mcg/mL) (Mean)
Cycle 1 Day 1 (in absence of trastuzumab)Cycle 2 Day 1 (in presence of trastuzumab)
Trastuzumab + Docetaxel + Carboplatin115123

[back to top]

Geometric Mean Ratio of Cmax/D of Carboplatin

The geometric mean ratio of Cmax of carboplatin was defined as the Cmax/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by Cmax/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab). (NCT00927589)
Timeframe: 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)

Interventionratio (Geometric Mean)
Trastuzumab + Docetaxel + Carboplatin1.02

[back to top]

Geometric Mean Ratio of AUC0-6hr/D of Carboplatin

The geometric mean ratio of AUC0-6hr/D of carboplatin was defined as the AUC0-6hr/D of carboplatin on Cycle 1 Day 1 (in the absence of trastuzumab) divided by AUC0-6hr/D of carboplatin on Cycle 2 Day 1 (in the presence of trastuzumab). (NCT00927589)
Timeframe: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)

Interventionratio (Geometric Mean)
Trastuzumab + Docetaxel + Carboplatin1.07

[back to top]

Change From Baseline in Corrected QT Interval Using Fridericia's Correction (QTcF) at Trastuzumab Steady State

Triplicate 12-lead electrocardiogram (ECG) measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR). Trastuzumab steady state was defined as the average of the 2 ECG measurements collected on Cycle 1 Day 8 (C1D8) and Cycle 2 Day 1 (C2D1) after the trastuzumab infusion. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1

Interventionmilliseconds (msec) (Mean)
Trastuzumab + Docetaxel + Carboplatin-8.4

[back to top]

Change From Baseline in Corrected QT Interval Using Bazett's Correction (QTcB) at Trastuzumab Steady State

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Bazette's formula (QTcB = QT divided by square root of RR). Trastuzumab steady state was defined as the average of the 2 ECG measurements collected on Cycle 1 Day 8 and Cycle 2 Day 1 after the trastuzumab infusion. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 8 and Cycle 2 Day 1

Interventionmsec (Mean)
Trastuzumab + Docetaxel + Carboplatin-5.9

[back to top]

Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab

(NCT00927589)
Timeframe: 15 (±15) minutes prior to the start of the trastuzumab infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1

Interventionmcg/mL (Geometric Mean)
Cycle 1 Day 2 (n=57)Cycle 1 Day 8 (n=51)Cycle 2 Day 1 (n=48)Cycle 3 Day 1 (n=42)
Trastuzumab + Docetaxel + Carboplatin0.17838.838.729.7

[back to top]

Plasma Decay Half-Life (t1/2) of Carboplatin

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. (NCT00927589)
Timeframe: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)

Interventionhr (Mean)
Cycle 1 Day 1 (in absence of trastuzumab) (n=44)Cycle 2 Day 1 (in presence of trastuzumab) (n=43)
Trastuzumab + Docetaxel + Carboplatin22

[back to top]

Number of Participants Within Each Absolute QTc Interval Category

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum QTc less than or equal to (<=) 450 msec, greater than (>) 450 to <=470 msec, >470 to <= 500 msec, or >500 msec were reported. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionparticipants (Number)
QTcF<=450 msec: C1D2 30 min postdose (n=49)QTcF >450 to <=470 msec:C1D2 30min postdose (n=49)QTcF >470 to <=500 msec: C1D2 30min postdose(n=49)QTcF >500 msec: C1D2 30 min postdose (n=49)QTcF<=450 msec: C1D8 15 min predose (n=50)QTcF >450 to <=470 msec: C1D8 15 min predose(n=50)QTcF >470 to <=500 msec: C1D8 15 min predose(n=50)QTcF >500 msec: C1D8 15 min predose (n=50)QTcF<=450 msec: C1D8 30 min postdose (n=50)QTcF >450 to <=470 msec: C1D8 30min postdose(n=50)QTcF >470 to <=500 msec: C1D8 30min postdose(n=50)QTcF >500 msec: C1D8 30 min postdose (n=50)QTcF<=450 msec: C2D1 15 min predose (n=48)QTcF >450 to <=470 msec: C2D1 15 min predose(n=48)QTcF >470 to <=500 msec: C2D1 15 min predose(n=48)QTcF >500 msec: C2D1 15 min predose (n=48)QTcF<=450 msec: C2D1 30 min postdose (n=48)QTcF >450 to <=470 msec: C2D1 30min postdose(n=48)QTcF >470 to <=500 msec: C2D1 30min postdose(n=48)QTcF >500 msec: C2D1 30 min postdose (n=48)QTcB<=450 msec: C1D2 30 min postdose (n=49)QTcB >450 to <=470 msec:C1D2 30min postdose (n=49)QTcB >470 to <=500 msec: C1D2 30min postdose(n=49)QTcB >500 msec: C1D2 30 min postdose (n=49)QTcB<=450 msec: C1D8 15 min predose (n=50)QTcB >450 to <=470 msec: C1D8 15 min predose(n=50)QTcB >470 to <=500 msec: C1D8 15 min predose(n=50)QTcB >500 msec: C1D8 15 min predose (n=50)QTcB<=450 msec: C1D8 30 min postdose (n=50)QTcB >450 to <=470 msec: C1D8 30min postdose(n=50)QTcB >470 to <=500 msec: C1D8 30min postdose(n=50)QTcB >500 msec: C1D8 30 min postdose (n=50)QTcB<=450 msec: C2D1 15 min predose (n=48)QTcB >450 to <=470 msec: C2D1 15 min predose(n=48)QTcB >470 to <=500 msec: C2D1 15 min predose(n=48)QTcB >500 msec: C2D1 15 min predose (n=48)QTcB<=450 msec: C2D1 30 min postdose (n=48)QTcB >450 to <=470 msec: C2D1 30min postdose(n=48)QTcB >470 to <=500 msec: C2D1 30min postdose(n=48)QTcB >500 msec: C2D1 30 min postdose (n=48)
Trastuzumab + Docetaxel + Carboplatin444104910048200480004800036102141720399204341043500

[back to top]

Number of Participants With New Abnormal U Waves on ECG

The incidence of abnormal U-wave changes from baseline was determined based on centrally read ECG tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: a large U wave, inverted U wave, or T-U fusion compared with baseline was considered an abnormal significant change from baseline. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionparticipants (Number)
C1D2 30 min postdose (n=49)C1D8 15 min predose (n=50)C1D8 30 min postdose (n=50)C2D1 15 min predose (n=48)C2D1 30 min postdose (n=48)
Trastuzumab + Docetaxel + Carboplatin00000

[back to top]

Number of Participants With New Abnormal T Waves on ECG

The incidence of abnormal T-wave changes from baseline was determined based on centrally read ECG tracings comparing each of the three triplicate readings from the post baseline ECG time points to the baseline ECG reading. At each time point, if at least one of the three triplicate readings was abnormal, the participant was counted as abnormal for that ECG timepoint as follows: an inverted T, flat T, or biphasic T compared with baseline was considered an abnormal significant change from baseline. Additionally, nonspecific T-wave changes from baseline were considered as abnormal nonsignificant changes from baseline. T-wave changes from baseline due to ventricular conduction or left ventricular hypertrophy strain were considered not evaluable. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionparticipants (Number)
C1D2 30 min postdose (n=49)C1D8 15 min predose (n=50)C1D8 30 min postdose (n=50)C2D1 15 min predose (n=48)C2D1 30 min postdose (n=48)
Trastuzumab + Docetaxel + Carboplatin00000

[back to top]

Number of Participants With Increase From Baseline in QTc Interval

Triplicate 12-lead ECG measurements (each recording separated by approximately 2 minutes) were performed and average was calculated. The time corresponding to beginning of depolarization to repolarization of the ventricles (QT interval) was adjusted for RR interval using QT and RR from each ECG by Fridericia's formula (QTcF = QT divided by cube root of RR) and by Bazette's formula (QTcB = QT divided by square root of RR). Participants with maximum increase from baseline of =>30msec, 30 to <60 msec (borderline) and >=60 msec (prolonged) were summarized. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionparticipants (Number)
QTcF<=30 msec: C1D2 30 min postdose (n=49)QTcF >30 to <=60 msec:C1D2 30 min postdose (n=49)QTcF >60 msec: C1D2 30 min postdose (n=49)QTcF<=30 msec: C1D8 15 min predose (n=50)QTcF >30 to <=60 msec: C1D8 15 min predose (n=50)QTcF >60 msec: C1D8 15 min predose (n=50)QTcF<=30 msec: C1D8 30 min postdose (n=50)QTcF >30 to <=60 msec: C1D8 30 min postdose (n=50)QTcF >60 msec: C1D8 30 min postdose (n=50)QTcF<=30 msec: C2D1 15 min predose (n=48)QTcF >30 to <=60 msec: C2D1 15 min predose (n=48)QTcF >60 msec: C2D1 15 min predose (n=48)QTcF<=30 msec: C2D1 30 min postdose (n=48)QTcF >30 to <=60 msec: C2D1 30min postdose (n=48)QTcF >60 msec: C2D1 30 min postdose (n=48)QTcB<=30 msec: C1D2 30 min postdose (n=49)QTcB >30 to <=60 msec:C1D2 30 min postdose (n=49)QTcB >60 msec: C1D2 30 min postdose (n=49)QTcB<=30 msec: C1D8 15 min predose (n=50)QTcB >30 to <=60 msec: C1D8 15 min predose (n=50)QTcB >60 msec: C1D8 15 min predose (n=50)QTcB<=30 msec: C1D8 30 min postdose (n=50)QTcB >30 to <=60 msec: C1D8 30 min postdose (n=50)QTcB >60 msec: C1D8 30 min postdose (n=50)QTcB<=30 msec: C2D1 15 min predose (n=48)QTcB >30 to <=60 msec: C2D1 15 min predose (n=48)QTcB >60 msec: C2D1 15 min predose (n=48)QTcB<=30 msec: C2D1 30 min postdose (n=48)QTcB >30 to <=60 msec: C2D1 30min postdose (n=48)QTcB >60 msec: C2D1 30 min postdose (n=48)
Trastuzumab + Docetaxel + Carboplatin4900500050004800480049005000491048004800

[back to top]

Number of Participants With Abnormal Changes in QRS Interval

Criteria for abnormal changes in QRS interval were defined as: >=25% change from baseline, an absolute value >110 msec, or >=25% change from baseline and an absolute value >110 msec. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionparticipants (Number)
>=25% change: C1D2 30 min postdose (n=49)Absolute value >110msec: C1D2 30min postdose(n=49)>=25%change and >110msec:C1D2 30min postdose(n=49)>=25% change: C1D8 15 min predose (n=50)Absolute value >110msec: C1D8 15 min predose(n=50)>=25%change and >110msec: C1D8 15min predose(n=50)>=25% change: C1D8 30 min postdose (n=50)Absolute value >110msec: C1D8 30min postdose(n=50)>=25%change and >110msec:C1D8 30min postdose(n=50>=25% change: C2D1 15 min predose (n=48)Absolute value >110msec: C2D1 15 min predose(n=48)>=25%change and >110msec: C2D1 15min predose(n=48)>=25% change: C2D1 30 min postdose (n=48)Absolute value >110msec: C2D1 30min postdose(n=48)>=25%change and >110msec:C2D1 30min postdose(n=48)
Trastuzumab + Docetaxel + Carboplatin040040040040040

[back to top]

Number of Participants With Abnormal Changes in PR Interval

Criteria for abnormal changes in PR interval were defined as: =>25 percentage (%) change from baseline, an absolute value >200 msec, or >=25% change from baseline and an absolute value >200 msec. (NCT00927589)
Timeframe: Baseline, Cycle 1 Day 2 (30 minutes postdose), Cycle 1 Day 8 (15 minutes predose), Cycle 1 Day 8 (30 minutes postdose), Cycle 2 Day 1 (15 minutes predose), and Cycle 2 Day 1 (30 minutes postdose)

Interventionparticipants (Number)
>=25% change: C1D2 30 min postdose (n=49)Absolute value >200msec: C1D2 30min postdose(n=49)>=25%change and >200msec:C1D2 30min postdose(n=49)>=25% change: C1D8 15 min predose (n=50)Absolute value >200msec: C1D8 15 min predose(n=50)>=25%change and >200msec: C1D8 15min predose(n=50)>=25% change: C1D8 30 min postdose (n=50)Absolute value >200msec: C1D8 30min postdose(n=50)>=25%change and >200msec:C1D8 30min postdose(n=50)>=25% change: C2D1 15 min predose (n=48)Absolute value >200msec: C2D1 15 min predose(n=48)>=25%change and >200msec: C2D1 15min predose(n=48)>=25% change: C2D1 30 min postdose (n=48)Absolute value >200msec: C2D1 30min postdose(n=48)>=25%change and >200msec:C2D1 30min postdose(n=48)
Trastuzumab + Docetaxel + Carboplatin020111010241241

[back to top]

Maximum Observed Serum Concentration (Cmax) of Trastuzumab

(NCT00927589)
Timeframe: 30 (±15) minutes after the end of the infusion on Cycle 1 Day 2, Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 3 Day 1

Interventionmcg/mL (Geometric Mean)
Cycle 1 Day 2 (n=57)Cycle 1 Day 8 (n=51)Cycle 2 Day 1 (n=48)Cycle 3 Day 1 (n=42)
Trastuzumab + Docetaxel + Carboplatin146.3187.1179.1181.5

[back to top]

Maximum Observed Plasma Concentration (Cmax) of Carboplatin

(NCT00927589)
Timeframe: 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)

InterventionMicrogram per milliliter (mcg/mL) (Mean)
Cycle 1 Day 1 (in absence of trastuzumab)Cycle 2 Day 1 (in presence of trastuzumab)
Trastuzumab + Docetaxel + Carboplatin5152

[back to top]

Dose-Normalized Cmax (Cmax/D) of Carboplatin

Dose normalized Cmax is the maximum observed concentration of carboplatin in plasma normalized for different dose levels. (NCT00927589)
Timeframe: 0 to 5 minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)

Intervention(mcg/mL)/(min*mg/mL) (Mean)
Cycle 1 Day 1 (in absence of trastuzumab)Cycle 2 Day 1 (in presence of trastuzumab)
Trastuzumab + Docetaxel + Carboplatin99

[back to top]

Dose-Normalized AUC0-6hr (AUC0-6hr/D) of Carboplatin

AUC0-6hr/D = Area under the plasma concentration versus time curve from 0 to 6 hours post-infusion, normalized by carboplatin dose level. (NCT00927589)
Timeframe: 0 to 5, 60 (±5), 120 (±10), 240 (±10), and 360 (±15) minutes after end of infusion on Cycle 1 Day 1 (in absence of trastuzumab) and Cycle 2 Day 1 (in presence of trastuzumab)

Intervention(hr*mcg/mL)/(min*mg/mL) (Mean)
Cycle 1 Day 1 (in absence of trastuzumab)Cycle 2 Day 1 (in presence of trastuzumab)
Trastuzumab + Docetaxel + Carboplatin1921

[back to top]

Tumour Response Rate

Objective response rate defined as participants with a complete or partial response according to RECIST (NCT00929162)
Timeframe: While receiving paclitaxel + carboplatin study visits were aliged with its administration ie every 3 weeks, then every 6 weeks (up to 2 years)

InterventionParticipants (Number)
ZD4054+Paclitaxel+Carboplatin21
Placebo+Paclitaxel+Carboplatin34

[back to top]

Progression Free Survival

Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method. (NCT00929162)
Timeframe: Patients were followed for progression up to 2 years

InterventionMonths (Median)
ZD4054+Paclitaxel+Carboplatin7.6
Placebo+Paclitaxel+Carboplatin10.0

[back to top]

Overall Survival

Overall survival was defined as the time from study enrollment to the time of death from any cause or last follow-up. (NCT00936702)
Timeframe: Time from registration to death or last follow-up (up to 3 years)

Interventionmonths (Median)
Treatment (Carboplatin, Paclitaxel, and Everolimus)10.1

[back to top]

Time to Treatment Failure

Time to treatment failure was defined to be the time from the date of registration to the date at which the participant is removed from treatment due to progression, adverse events, or refusal. (NCT00936702)
Timeframe: Up to 3 years

Interventionmonths (Median)
Treatment (Carboplatin, Paclitaxel, and Everolimus)3.1

[back to top]

Progression-free Survival

The progression-free survival (PFS) was defined as the time from date of registration to the documentation of disease progression or death as a result of any cause, whichever comes first. (NCT00936702)
Timeframe: Time from registration to the disease progression or death (up to 3 years)

Interventionmonths (Median)
Treatment (Carboplatin, Paclitaxel, and Everolimus)4.1

[back to top]

Percentage of Participants With Confirmed Tumor Responses

"Confirmed tumor response was defined to be either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.~Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria:~Complete Response (CR): disappearance of all target lesions;~Partial Response (PR) 30% decrease in sum of longest diameter of target lesions;" (NCT00936702)
Timeframe: First 6 Cycles of treatment (an average of 6 months)

Interventionpercentage of participants (Number)
Treatment (Carboplatin, Paclitaxel, and Everolimus)36

[back to top]

Duration of Response

Duration of response was defined for all evaluable participants who have achieved an objective response as the date at which the participant's objective status is first noted to be either CR or PR to the date progression is documented. (NCT00936702)
Timeframe: Up to 3 years

Interventionmonths (Median)
Treatment (Carboplatin, Paclitaxel, and Everolimus)5.8

[back to top]

Duration of Response

Duration of response was defined as the interval between the date of the first documented response by RECIST to the date of first disease progression or death, whichever occurred earlier. Disease progression was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the appearance of 1 or more new lesions or the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level. (NCT00937560)
Timeframe: Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)

InterventionMonths (Median)
RECIST only (N=77)CA-125 level only (N=98)RECIST and CA-125 level combined (N=116)
Bevacizumab + Paclitaxel + Carboplatin14.717.517.4

[back to top]

Progression-free Survival

Progression-free survival was defined as the time from the first administration of any study treatment to the first disease progression using Response Evaluation Criteria In Solid Tumors (RECIST) or death from any cause, whichever occurred first. (NCT00937560)
Timeframe: Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)

InterventionMonths (Median)
Bevacizumab + Paclitaxel + Carboplatin23.7

[back to top]

Biological Progression-free Interval

Biological progression-free interval is defined as the interval from the date of the first administration of any study treatment to the date of the first documented serial elevation of the ovarian cancer mucin CA-125. More precisely, this is defined as the first documented increase in CA-125 levels as follows: (1) CA-125 greater than or equal to 2 times the upper level of normal (ULN) on 2 occasions at least 1 week apart (for patients with CA-125 within normal range pre-treatment) or (2) CA-125 greater than or equal to 2 times the ULN on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment and initial normalisation of CA-125 on-treatment) or (3) CA-125 greater than or equal to 2 times the nadir value, which is the lowest observed CA-125 value per patient on 2 occasions at least 1 week apart (for patients with elevated CA-125 pre-treatment which never normalised). (NCT00937560)
Timeframe: Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)

InterventionMonths (Median)
Bevacizumab + Paclitaxel + CarboplatinNA

[back to top]

Percentage of Participants With an Objective Response

An objective response was defined as either a complete response (CR) or a partial response (PR). Using the Response Evaluation Criteria in Solid Tumors (RECIST), a CR was defined as the disappearance of all target lesions and all non-target lesions, normalization of tumor marker level, and no new lesions and a PR was defined as the disappearance of all target lesions and persistence of ≥ 1 non-target lesions and/or the maintenance of tumor marker level above the normal limits, or, at least a 30% decrease in the sum of the longest diameter of target lesions, and no new lesions or unequivocal progression of existing non-target lesions. Only participants with measurable disease were included in the analysis according to RECIST only. Only participants with a Baseline ovarian cancer mucin CA-125 level ≥ 2 times the upper limit of normal who had a ≥ 50% reduction of CA-125 from Baseline were included in the analysis according to CA-125 level. (NCT00937560)
Timeframe: Baseline to the data cut-off date of 19 Jul 2012 for analysis of the primary Outcome Measure (follow-up time up to 3 years, 1 month)

InterventionPercentage of participants (Number)
RECIST only (N=91)CA-125 level only (N=101)RECIST and CA-125 level combined (N=126)
Bevacizumab + Paclitaxel + Carboplatin84.697.092.1

[back to top]

Overall Survival at 1 Year and 2 Years

Reported are the percentage of participants that were alive at 1 year and 2 years after enrolling in the study. (NCT00937560)
Timeframe: Baseline to Year 2

InterventionPercentage of participants (Number)
Year 1Year 2
Bevacizumab + Paclitaxel + Carboplatin97.792.1

[back to top]

Patient-reported Peripheral Neuropathy Symptoms

Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less peripheral neuropathy symptoms. (NCT00942357)
Timeframe: Prior to study treatment (baseline), Arm 1: 1 week post completion of radiation therapy, Arm 2: Prior to cycle 3 (6 weeks post starting of study treatment), 18 weeks post the starting of study treatement, 70 weeks post the starting of study treatment

,
Interventionunit on a scale (Least Squares Mean)
Baseline6 weeks18 weeks70 weeks
Arm I (Cisplatin, Radiation Therapy, Paclitaxel, Carboplatin)14.914.410.411.8
Arm II (Paclitaxel and Carboplatin)15.012.49.911.6

[back to top]

Number of Participants With Late Adverse Events as Graded by the NCI CTCAE Version 3.0

The maximum grade of Adverse events reported during follow-up until progression of disease, a change of therapy or otherwise off study for a maximum of 3 years without regard to attribution. General guidelines for severity of adverse events are as follows: Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening and Grade 5 is death. (NCT00942357)
Timeframe: Assessed every 6 months for 3 years

,
InterventionParticipants (Count of Participants)
Grade 1Grade 2Grade 3Grade 4Grade 5
Arm I (Cisplatin, Radiation Therapy, Paclitaxel, Carboplatin)857145141
Arm II (Paclitaxel and Carboplatin)96793374

[back to top]

Number of Participants With Recurrence, Progression or Death

Number of participants enrolled with recurrence or progression of disease or death up to date of last contact. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions. (NCT00942357)
Timeframe: Disease was to be assessed at baseline, end of treatment and every 6 months for two years, and annually up to 5 years.

Interventionparticipants (Number)
Arm I (Cisplatin, Radiation Therapy, Paclitaxel, Carboplatin)132
Arm II (Paclitaxel and Carboplatin)139

[back to top]

Number of Participants With Acute Adverse Effects as Graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version (CTCAE) Version 3.0

The maximum grade of all treatment emergent adverse events without regard to attribution. General guidelines for severity of adverse events are as follows: Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life threatening and Grade 5 is death. (NCT00942357)
Timeframe: Assessed throughout the treatment period and for 21-30 days after discontinuation of treatment

,
InterventionParticipants (Count of Participants)
Grade 1Grade 2Grade 3Grade 4Grade 5
Arm I (Cisplatin, Radiation Therapy, Paclitaxel, Carboplatin)5139154480
Arm II (Paclitaxel and Carboplatin)151181191053

[back to top]

Patient-reported Quality of Life (QOL)

Patient reported quality of life was measured with the Treatment Outcome Index of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). It is a scale for assessing general QOL of endometrial cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Endometrium Cancer subscale (16 items). Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The FACT-En TOI score is calculated as the sum of the subscale scores, ranges are 0-120 with a large score suggesting a better QOL. (NCT00942357)
Timeframe: Prior to study treatment (baseline), Arm 1: 1 Week post completion of radiation therapy, Arm 2: Prior to cycle 3 (6 weeks post starting of study treatment), 18 weeks post the starting of study treatment, 70 weeks post the starting of study treatment

,
Interventionunits on a scale (Least Squares Mean)
Baseline6 weeks18 weeks70 weeks
Arm I (Cisplatin, Radiation Therapy, Paclitaxel, Carboplatin)98.489.587.896.0
Arm II (Paclitaxel and Carboplatin)97.690.993.099.4

[back to top]

Best Overall Response and Objective Response Rate Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer

The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], unconfirmed CR, unconfirmed PR, stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdraws from the study. If there is no tumor assessment after the first dose of study drug, the best overall response is classified as Inevaluable. CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD defined as at least a 20% increase in the sum of diameters of target lesions. Objective response rate was defined as confirmed CR and confirmed PR. (NCT00945191)
Timeframe: Baseline up to first documented objective response, disease progression, or study withdrawal, up to 1 year 10 months

InterventionParticipants (Count of Participants)
Confirmed CR after 6 cycles (18 weeks) of treatmentConfirmed CRConfirmed PRObjective Response (Confirmed CR + Confirmed PR)Unconfirmed CRUnconfirmed PRStable disease (SD)Progressive disease (PD)InevaluableBest overall response of SD or better
CS-1008 in Combination With Paclitaxel/Carboplatin0012120451221

[back to top]

Change From Baseline in the Sum of Longest Diameters of Target Lesions Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer

A sum of the diameters for all target lesions will be calculated and reported as the baseline sum of diameters, defined as the last non-missing value before initial administration of study treatment. The baseline sum of diameters will be used as reference for characterization of the objective tumor response. The change from baseline in the sum of longest diameters of target lesions is being reported. Negative values indicate an improvement in tumor reduction. (NCT00945191)
Timeframe: Baseline to Cycle 3, Week 3 Day 1; Cycle 6, Week 3 Day 1 (each cycle 21 days) up to end of study, approximately 1 year 10 months postdose

Interventionmm (Mean)
Cycle 3, Week 3 Day 1Cycle 6, Week 3 Day 1Minimum post-treatment value
CS-1008 in Combination With Paclitaxel/Carboplatin-39.0-52.4-48.3

[back to top]

Participants With Treatment-Emergent Adverse Events Grade 3 or Higher by System Organ Class and Preferred Term Following Treatment With CS-1008 in Combination With Chemotherapy (Paclitaxel/Carboplatin) in Locally Advanced or Metastatic Ovarian Cancer

Treatment-emergent adverse events (TEAEs) were defined as those events that occur, having been absent before the study, or worsen in severity after the initiation of CS-1008 and/or paclitaxel/docetaxel/carboplatin administration. All adverse events (AEs) were graded (1 to 5) according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0, where Grade 1 was mild, Grade 2 moderate, Grade 3 severe, Grade 4 life-threatening or disabling, and Grade 5 death related to AE. (NCT00945191)
Timeframe: Baseline up to 30 days after last dose, up to 1 year 10 months postdose

InterventionParticipants (Count of Participants)
Any TEAE ≥Grade 3Any Preferred Term Within Blood and Lymphatic System DisordersAnaemiaFebrile neutropeniaLeukopeniaNeutropeniaPancytopeniaThrombocytopeniaAny Preferred Term Within Gastrointestinal DisordersAbdominal painAscitesConstipationEnterocolitisGastrooesophageal reflux diseaseSmall intestinal obstructionAny Preferred Term Within General Disorders and Administration Site ConditionsChillsFatigueAny Preferred Term Within Infections and InfestationsAbdominal abscessUrinary tract infectionWound infection staphylococcalAny Preferred Term Within InvestigationsProthrombin time prolongedAny Preferred Term Within Metabolism and Nutrition DisordersDehydrationElectrolyte imbalanceHyperglycaemiaHypokalaemiaHyponatraemiaHypophosphataemiaAny Preferred Term Within Musculoskeletal and Connective Tissue DisordersArthralgiaBack painMusculoskeletal painAny Preferred Term Within Renal and Urinary DisordersRenal vein thrombosisAny Preferred Term Within Vascular DisordersVenous thrombosis
CS-1008 in Combination With Paclitaxel/Carboplatin222061218176121113211313111521121121111111

[back to top]

Overall Survival (OS) of EGFR FISH-positive Patients

From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact. (NCT00946712)
Timeframe: Patients will be followed every 3 weeks while on protocol treatment. Once off all protocol treatment, patients will be followed every 6 months until death or up to 3 years

InterventionMonths (Median)
Arm I (Chemo +/- Bevacizumab)9.8
Arm II (Chemo, Cetuximab, +/- Bevacizumab)13.4

[back to top]

Progression-free Survival (PFS) of EGFR FISH-positive Patients by Institutional Review

From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as assessed by the treating investigator.Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using RECIST 1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00946712)
Timeframe: Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.

Interventionmonths (Median)
Arm I (Chemo +/- Bevacizumab)4.8
Arm II (Chemo, Cetuximab, +/- Bevacizumab)5.4

[back to top]

Progression-Free Survival (PFS) of the Entire Study Population by Institutional Review

From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause, whichever comes first by Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as assessed by the treating investigator.Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using RECIST 1.1, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00946712)
Timeframe: Disease assessment will be repeated every 6 weeks until disease progression while on treatment. After off treatment, the frequency of disease assessment may be reduced to every 3 months until disease progression.

InterventionMonths (Median)
Arm I (Chemo +/- Bevacizumab)4.5
Arm II (Chemo, Cetuximab, +/- Bevacizumab)4.6

[back to top]

Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in the Entire Study Population

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT00946712)
Timeframe: Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.

Interventionpercentage of analyzed participants (Number)
Arm I (Chemo +/- Bevacizumab)36
Arm II (Chemo, Cetuximab, +/- Bevacizumab)42

[back to top] [back to top]

Response Rate (Confirmed Plus Unconfirmed, Complete and Partial Responses) in the Subset of Patients With Measurable Disease in EGFR FISH-positive Patients

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT00946712)
Timeframe: Disease assessment will be repeated every 6 weeks for the first 9 months and every 3 months thereafter, until disease progression.

Interventionpercentage of analyzed participants (Number)
Arm I (Chemo +/- Bevacizumab)43
Arm II (Chemo, Cetuximab, +/- Bevacizumab)47

[back to top]

Overall Survival (OS) in the Entire Study Population

From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact. (NCT00946712)
Timeframe: Patients will be followed every 3 weeks while on protocol treatment. Once off all protocol treatment, patients will be followed every 6 months until death or up to 3 years

Interventionmonths (Median)
Arm I (Chemo +/- Bevacizumab)9.2
Arm II (Chemo, Cetuximab, +/- Bevacizumab)10.9

[back to top]

Disease Control Rates Defined as Complete Response (CR), Partial Response (PR), and Stable Disease (SD)

Disease control rate was the percentage of participants with a confirmed CR, PR or SD, as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR was the disappearance of all target and non-target lesions; PR was a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion; SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Disease control rate was calculated as a total number of participants with CR or PR or SD divided by the total number of participants treated, then multiplied by 100. (NCT00948675)
Timeframe: Baseline to date of objective progressive disease up to 39.49 months

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin59.9
Paclitaxel + Carboplatin + Bevacizumab57.0

[back to top]

Overall Survival (OS)

OS was defined as the duration from the date of randomization to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the last date the participant was known to be alive. (NCT00948675)
Timeframe: Randomization to date of death from any cause up to 39.49 months

Interventionmonths (Median)
Pemetrexed + Carboplatin10.51
Paclitaxel + Carboplatin + Bevacizumab11.66

[back to top]

Percentage of Participants With Complete Response or Partial Response (Overall Tumor Response Rate)

Overall Response rate (ORR) was the percentage of participants with a confirmed complete response (CR) or partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR was the disappearance of all target and non-target lesions; PR was a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions. ORR was calculated as a total number of participants with CR or PR from the start of study treatment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100. (NCT00948675)
Timeframe: Baseline to date of objective progressive disease up to 39.49 months

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin23.6
Paclitaxel + Carboplatin + Bevacizumab27.4

[back to top]

Progression Free Survival (PFS)

PFS was defined as the duration from the date of randomization to the date of progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD was ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no PD or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy. (NCT00948675)
Timeframe: Randomization to measured progressive disease up to 39.49 months

Interventionmonths (Median)
Pemetrexed + Carboplatin4.44
Paclitaxel + Carboplatin + Bevacizumab5.45

[back to top]

Progression Free Survival Without Grade 4 Toxicity (G4PFS) as Measured by the Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0

G4PFS was defined as the duration from the date of randomization to the earliest occurrence date of one of the following three events: Common Terminology Criteria (CTC) grade 4 adverse events (G4AEs), or progressive disease (PD) or death from any cause, whichever occurred earlier. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who had no G4AEs, or PD, or death at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy. (NCT00948675)
Timeframe: Randomization to measured progressive disease or treatment discontinuation up to 39.49 months

Interventionmonths (Median)
Pemetrexed + Carboplatin3.91
Paclitaxel + Carboplatin + Bevacizumab2.86

[back to top]

Overall Survival

Estimate the median duration of overall survival in months. (NCT00951496)
Timeframe: Up to 10 years

InterventionMonths (Median)
Arm I (Paclitaxel, Carboplatin, Bevacizumab)75.4
Arm II (Paclitaxel, Bevacizumab, Carboplatin IP)74.2
Arm III (Paclitaxel IP, Bevacizumab, Cisplatin IP)67.6

[back to top]

Patient Reported Nausea

Nausea was measured with the a single item ,' I have nausea' from the FACT-O TOI, and was scored using a 5 point scale (0=not at all; 1=a little bit; 2=somewhat;3=quite a bit;4=very much) (NCT00951496)
Timeframe: Time points: Baseline, prior to cycle 4, prior to cycle 7, prior to cycle 13, prior to cycle 21, 84 weeks post starting treatment

,,
Interventionunits on a scale (Least Squares Mean)
BaselinePrior to cycle 4Prior to cycle 7Prior to cycle 13Prior to cycle 2184 Weeks
Arm I (Paclitaxel, Carboplatin, Bevacizumab)0.40.60.50.20.30.3
Arm II (Paclitaxel, Bevacizumab, Carboplatin IP)0.40.70.50.30.40.4
Arm III (Paclitaxel IP, Bevacizumab, Cisplatin IP)0.41.10.70.20.30.3

[back to top]

Patient Reported Quality of Life (QOL)

QOL was measured with the FACT-O TOI score. Means at baseline are raw means. Scores are reported at all time points in the outcome measure table. FACT-O TOI is Trial outcome index (TOI) of the Functional assessment of cancer therapy (FACT) for ovarian cancer (FACT-O). The FACT-O TOI is composed of three subscales; Physical Well Being (PWB) ( 7 items), and Ovarian Cancer subscale (OCS) (12 items). Each item in the FACT-O TOI are scored using a 5 point scale (0=not at all; 1=a little bit; 2=somewhat;3=quite a bit;4=very much). A subscale score is computed as long as more thatn 50% of subscale items have been answered. A total score of the FACT-O items provide valid responses and all three subscales have valid scores. A score of the FACT-) TOI is ranged 0-104 with a larger score indicating a more preferred state of health-related quality of life (HRQOL). (NCT00951496)
Timeframe: Time points: Baseline, prior to cycle 4, prior to cycle 7, prior to cycle 13, prior to cycle 21, up to 84 weeks post starting treatment

,,
InterventionUnits on a scale (Least Squares Mean)
BaselinePrior to cycle 4Prior to cycle 7Prior to cycle 13Prior to cycle 2184 weeks
Arm I (Paclitaxel, Carboplatin, Bevacizumab)68.567.869.177.377.778.3
Arm II (Paclitaxel, Bevacizumab, Carboplatin IP)67.465.668.277.176.977.7
Arm III (Paclitaxel IP, Bevacizumab, Cisplatin IP)67.761.965.778.478.279.4

[back to top]

Patient Reported Fatigue

Patient reported fatigue as measured with the Functional Assessment of Chronic Illness Therapy- Fatigue scale (FACIT-Fatigue). The FACIT-Fatigue contains 13 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Fatigue score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The FACIT-Fatigue score ranges 0-52 with a large score suggesting less fatigue. (NCT00951496)
Timeframe: Time points: Baseline, prior to cycle 4, prior to cycle 7, prior to cycle 13, prior to cycle 21, 84 weeks post starting treatment

,,
Interventionunits on a scale (Least Squares Mean)
BaselinePrior to cycle 4Prior to cycle 7Prior to cycle 13Prior to cycle 2184 weeks
Arm I (Paclitaxel, Carboplatin, Bevacizumab)35.332.532.735.735.535.7
Arm II (Paclitaxel, Bevacizumab, Carboplatin IP)35.132.032.735.535.136.0
Arm III (Paclitaxel IP, Bevacizumab, Cisplatin IP)35.331.332.435.936.336.5

[back to top]

Median Progression-free Survival

Estimate the median duration of progression-free survival in months. Progression is defined using Response Evaluation Criteria in Solid Tumors criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT00951496)
Timeframe: Progression-free survival is measured from date of randomization until first indication of progression based on RECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment up to 10 years.

Interventionmonths (Median)
Arm I (Paclitaxel, Carboplatin, Bevcizumab IV)24.9
Arm II (Paclitaxel,carboplatinIP, Bevacizumab IP)27.3
Arm III (Paclitaxel IP, Cisplatin, Bevacizumab)26.0

[back to top]

Patient Reported Neurotoxicity (Ntx)

The FACT/GOG-NTX subscale (short version) contains 4 items measuring sensory neuropathy. Each item is scored using a 5 point Likert scale (0=not at all; 1=a little bit;2=somewhat;3=quite a bit; 4=very much). For each item, reversal was performed prior to score calculation so that a large score suggests less symptoms. According to the FACIT measurement system, the subscale score was calculated as the summation of the individual item scores if more than 50% of a subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the subscale. The Ntx subscale score ranges from 0-16 with a large subscale score suggesting less symptom or better QOL. (NCT00951496)
Timeframe: Time points: Baseline, prior to cycle 4, prior to cycle 7, prior to cycle 13, prior to cycle 21, 84 weeks post starting treatment

,,
InterventionUnits on a scale (Least Squares Mean)
BaselinePrior to cycle 4Prior to cycle 7Prior to cycle 13Prior to cycle 2184 weeks
Arm I (Paclitaxel, Carboplatin, Bevacizumab)15.412.910.411.111.411.9
Arm II (Paclitaxel, Bevacizumab, Carboplatin IP)15.413.010.310.511.111.4
Arm III (Paclitaxel IP, Bevacizumab, Cisplatin IP)15.413.610.99.211.011.5

[back to top]

Patients With Adverse Events by Treatment Group, as Defined by NCI CTCAE (Common Terminology Criteria for Adverse Events Version 3.0) Version 3.0

Eligible and treated patients. CTCAE includes grades 1-5. Grade refers to the severity of the adverse event. Grades 0 listed should be interpreted to mean there were no subjects in the arm with a toxicity to report. Grade 1 toxicities are mild; asymptomatic or mild symptoms. Grade 2 toxicities are moderate; minimal, local or noninvasive intervention indicated. Grade 3 toxicities are severe or medically significant but not immediately life-threatening. Grade 4 toxicities are life threatening. Grade 5 is death related to adverse event. (NCT00951496)
Timeframe: During treatment and up to 30 days after end of treatment

,,
InterventionParticipants (Count of Participants)
Adverse Event Grade 0Adverse Event Grade 1Adverse Event Grade 2Adverse Event Grade 3Adverse Event Grade 4Adverse Event Grade 5
Arm I (Paclitaxel, Carboplatin, Bevcizumab IV)01482691858
Arm II (Paclitaxel,carboplatinIP, Bevacizumab IP)00463001586
Arm III (Paclitaxel IP, Cisplatin, Bevacizumab)105224619910

[back to top]

Objective Response Rate

Percentage of participants with an objective response (complete response or partial response) based on Response Assessment in Neuro-Oncology (RANO) criteria. A complete response is defined as disappearance of all enhancing tumor on contrast enhanced MRI scan. Patient must be off steroids or only on adrenal maintenance doses. A partial response is defined as greater than or equal to a 50% reduction in the size (products of the largest perpendicular diameters) for all enhancing lesions. No new lesions may arise. Steroids must be stable or decreasing dose. (NCT00953121)
Timeframe: 34 months

Interventionparticipants (Number)
Grade IV, No Bevacizumab Failure0
Grade III, No Bevacizumab Failure0
Grade IV, Bevacizumab Failure0

[back to top]

6 Month Progression-free Survival

Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Response Assessment in Neuro-Oncology (RANO) criteria, or to death due to any cause. Progression is defined as greater than or equal to a 25% increase in the product of the largest perpendicular diameters of any enhancing lesion or any new enhancing tumor on MRI scans. Patients may also be classified as progressive disease with significant neurologic decline felt to be due to underlying tumor and not attributable to co-morbid event or concurrent medication regardless of MRI findings. (NCT00953121)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Grade IV, No Bevacizumab Failure47.5
Grade III, No Bevacizumab Failure71.1
Grade IV, Bevacizumab Failure24.0

[back to top]

Median Overall Survival (OS)

Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up had OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve. (NCT00953121)
Timeframe: 40 months

Interventionmonths (Median)
Grade IV, No Bevacizumab Failure9.3
Grade III, No Bevacizumab Failure16.0
Grade IV, Bevacizumab Failure5.9

[back to top]

Median Progression Free Survival (PFS)

Time in months from the start of study treatment to the date of first progression according to RANO criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. (NCT00953121)
Timeframe: 40 months

Interventionmonths (Median)
Grade IV, No Bevacizumab Failure5.9
Grade III, No Bevacizumab Failure10.0
Grade IV, Bevacizumab Failure3.6

[back to top]

Safety of Bevacizumab (Avastin) in Combination With Irinotecan and Carboplatin

Number of patients experiencing a toxicity greater than or equal to grade 2 treatment-related toxicity (NCT00953121)
Timeframe: 34 months

Interventionparticipants (Number)
Grade IV, No Bevacizumab Failure39
Grade III, No Bevacizumab Failure39
Grade IV, Bevacizumab Failure23

[back to top]

Patient-Reported Quality of Life (QOL) - Baseline

Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). The FACT-En TOI is a scale for assessing general QOL of endometrial cancer patients. The FACT-En TOI score ranges 0-120 with a large score suggesting better QOL. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Baseline - Prior to study treatment

Interventionunits on a scale (time point) (Mean)
Regimen I - Uterine and Non-Uterine Subjects96.2
Regimen II - Uterine and Non-Uterine Subjects97.5

[back to top]

Overall Survival

Measured in months from randomization to last contact or death. Primary analysis was restricted to the eligible uterine carcinosarcoma cohort. (NCT00954174)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 115 months.

Interventionmonths (Median)
Regimen I- Uterine Carcinsarcoma Subjects37.3
Regimen II - Uterine Carcinsarcoma Subjects29

[back to top]

Patient Reported Peripheral Neuropathy Symptoms - Baseline

Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 11 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). . The Ntx score ranges 0-44 with a large score suggesting less peripheral neuropathy symptoms. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Baseline (Pre cycle 1)

Interventionunits on a scale-baseline (Mean)
Regimen I - Uterine and Non-Uterine Subjects40.2
Regimen II - Uterine and Non-Uterine Subjects41.0

[back to top]

Patient Reported Quality of Life (QOL) - Post Baseline

Patient reported quality of life was measured with the Treatment Outcome Index (TOI) of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-En TOI). The FACT-En TOI is a scale for assessing general QOL of endometrial cancer patients. The FACT-En TOI score ranges 0-120 with a large score suggesting better QOL. Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Prior to cycle 3, Prior to cycle 6, 30 weeks post cycle 1.

,
Interventionunits on a scale (time point) (Least Squares Mean)
Pre-cycle 3Pree-cycle 630 weeks post cycle 1
Regimen I - Uterine and Non-Uterine Subjects93.391.698.0
Regimen II - Uterine and Non-Uterine Subjects93.391.697.6

[back to top]

Incidence of Adverse Events as Assessed by CTCAE Version 3.0

Maximum grade experienced among all treated and eligible patients. The grades are described by severity. Grade 1 is the lowest (most mild) and Grade 5 being death (most severe). Adverse events were analyzed across cohorts since disease site was considered independent of AEs. (NCT00954174)
Timeframe: Patients were assessed for adverse events during active protocol treatment and up to 30 days after the last cycle of treatment on the protocol.

,
InterventionParticipants (Count of Participants)
Grade 1Grade 2Grade 3Grade 4Grade 5
Regimen I - Uterine and Non-Uterine Subjects3221071306
Regimen II - All Uterine and Non-Uterine Subjects38097613

[back to top]

Patient-reported Peripheral Neuropathy Symptoms - Post Baseline

Patient reported peripheral neuropathy symptoms was measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 11 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). The Ntx score ranges 0-44 with a large score suggesting less peripheral neuropathy symptoms.Quality of Life was analyzed across cohorts since disease site was considered independent of Quality of Life. (NCT00954174)
Timeframe: Prior to cycle 3, Prior to cycle 6, 30 weeks post cycle 1

,
Interventionunits on a scale (Least Squares Mean)
Prior to cycle 3Prior to cycle 630 weeks post cycle 1
Regimen I - Uterine and Non-Uterine Subjects37.234.134.8
Regimen II - Uterine and Non-Uterine Subjects37.034.234.9

[back to top]

Duration of Progression-free Survival

Measured in months from randomization to last contact or the earlier of the date of progression or death. (NCT00954174)
Timeframe: Approximately 9 years and 7 months

Interventionmonths (Median)
Regimen I - Uterine Carcinsarcoma Subjects16.3
Regimen II - Uterine Carcinsarcoma Subjects11.7
Regimen III - Non-uterine Carcinsarcoma Subjects14.6
Regimen IV - Non-uterine Carcinsarcoma Subjects10.3

[back to top]

Part 2: Number of Participants With Each Type of Response Evaluation Criteria in Solid Tumors (RECIST)-Determined Overall Best Response

Overall best response was determined by RECIST criteria. Types of overall response could be: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Not Assessable (NA) or Incomplete Response/Stable Disease (IR/SD). (NCT00954512)
Timeframe: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)

,,,,
InterventionParticipants (Number)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Not Assessable (NA)Incomplete Response/Stable Disease (IR/SD)
Regimen A: FOLFIRI (± Cetuximab) + Robatumumab000200
Regimen B: Carboplatin + Paclitaxel + Robatumumab002100
Regimen D: Trastuzumab + Robatumumab001100
Regimen E: mTor Inhibitor (Everolimus) + Robatumumab002100
Regimen F: Gemcitabine (± Erlotinib) + Robatumumab001100

[back to top]

Part 1: Number of Participants Who Experienced One or More Adverse Events (AEs)

An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to this study drug. AEs may include the onset of new illness and the exacerbation of pre-existing conditions. (NCT00954512)
Timeframe: Up to ~30 days after the final dose of robatumumab (Up to ~14 months)

InterventionParticipants (Number)
Regimen A: FOLFIRI (± Cetuximab) + Robatumumab2
Regimen B: Carboplatin + Paclitaxel + Robatumumab3
Regimen D: Trastuzumab + Robatumumab2
Regimen E: mTor Inhibitor (Everolimus) + Robatumumab4
Regimen F: Gemcitabine (± Erlotinib) + Robatumumab4

[back to top]

Proportion of Patients With Objective Response

"Objective response was evaluated using the RECIST 1.1 criteria.~Objective response includes complete response (CR) and partial response (PR). Objective response is defined as disappearance of all target lesions or at least a 30% decrease in the sum of the diameters of target lesions. In addition, non-target lesions do not meet the criteria for disease progression and no new lesions were observed." (NCT00955305)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry and every 6 months if patient is 2-5 years from study entry; up to 5 years

InterventionProportion of participants (Number)
Arm A (CPB)0.462
Arm B (CPB+Cixutumumab)0.587

[back to top]

Overall Survival (OS)

Overall survival is defined as the time from randomization to death or date last known alive. (NCT00955305)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years

Interventionmonths (Median)
Arm A (CPB)16.2
Arm B (CPB+Cixutumumab)16.1

[back to top]

Progression-free Survival (PFS)

"Progression-free survival was defined as the time from randomization to progression or death without documentation of progression. For cases without progression, follow-up was censored at the date of last disease assessment without progression, unless death occurs within 3 months following the date last known progression-free, in which case the death was counted as a failure.~Progression was evaluated using RECIST 1.1 criteria and defined as:~At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm.~OR~Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions." (NCT00955305)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry; every 6 months if patient is 2 - 5 years from study entry; up to 5 years

Interventionmonths (Median)
Arm A (CPB)5.8
Arm B (CPB+Cixutumumab)7.0

[back to top]

Number of Participants Experiencing Adverse Events as a Measure of Toxicity

An adverse event (AE) is the development of an undesirable medical condition, or the deterioration of a preexisting medical condition (other than the condition that is being treated by the trial) following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. The number of participants experiencing such adverse events are reported here. (NCT00960297)
Timeframe: 45 months

InterventionParticipants (Count of Participants)
Carboplatin/Paclitaxel/Bevacizumab4

[back to top]

Overall Survival (OS) Rate at 24 Months

Overall Survival is time from date of treatment start until date of death due to any cause or last Follow-up within 24 months. (NCT00967369)
Timeframe: 24 months

Interventionpercentage of participants (Number)
BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide)70
ICE (Ifosfamide, Carboplatin, Etoposide)89

[back to top]

Progression Free Survival (PFS) Rate at 12 Months

Progression free survival time is defined as the time interval from treatment start to progression or death due to any cause whichever happens first. Participants will be censored at the last follow-up date, if an event(progression/death) is not observed during the follow-up. (NCT00967369)
Timeframe: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 100 months

Interventionpercentage of participants (Number)
BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide)50
ICE (Ifosfamide, Carboplatin, Etoposide)70

[back to top]

Overall Response After 3 Cycles of Botezomib Plus ICE (BICE) Versus Ifosfamide, Carboplatin, Etoposide (ICE) in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma

Response rates for Bortezomib, Ifosfamide, Carboplatin, Etoposide (BICE) and Ifosfamide, Carboplatin, Etoposide (ICE) treatment groups were assessed by the 1999 International Working Group (IWG)(CT alone) (Cheson et al., 1999) and compared to 2007 IWG (CT plus PET) (Cheson et al., 2007) criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT00967369)
Timeframe: From baseline to 3 cycles of treatment

,
InterventionParticipants (Count of Participants)
Overall ResponseComplete Response (CR)Partial Response (PR)Progressive Disease (PD)Stable Disease (SD)
BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide)73401
ICE (Ifosfamide, Carboplatin, Etoposide)61503

[back to top]

PET Scan Response After 3 Cycles of BICE Versus ICE Chemotherapy.

Response rates for BICE and ICE treatment groups will be assessed by 1999 IWG (CT alone) (Cheson et al., 1999) and compared to 2007 IWG (CT plus PET) (Cheson et al., 2007) criteria. (NCT00967369)
Timeframe: Baseline up to 1 year

,
InterventionParticipants (Count of Participants)
PET negativity : Complete Response (CR)PET negativity : Partial Response (PR)PET negativity : Stable Disease (SD)PET positivity : Partial Response (PR)PET positivity : Stable Disease (SD)PET positivity : Progressive Disease (PD)
BICE (Bortezomib, Ifosfamide, Carboplatin, Etoposide)300412
ICE (Ifosfamide, Carboplatin, Etoposide)641220

[back to top]

Disease Control Rate

Percentage of participants experiencing a CR (complete disappearance of measurable and evaluable disease without new lesions) or PR (>=50 percent decrease in sum of the products of diameters [SOPD] of index lesions compared to baseline SOPD, with no evidence of PD) confirmed by subsequent assessment no less than 28 days after criteria for response were first met) or stable disease [SD] (neither sufficient decrease to qualify for PR nor sufficient increase to qualify for PD) at least once no less than 42 days after first dose of trial treatment based on modified WHO criteria as assessed by IRC. (NCT00971932)
Timeframe: Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011

Interventionpercentage of participants (Number)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU)87.9

[back to top]

Overall Survival (OS) Time

Time from first administration of trial treatment to death. Participants without event are censored at the last date known to be alive or at the clinical cut-off date, whatever is earlier. (NCT00971932)
Timeframe: Time from first administration of trial treatment or last day known to be alive, reported between day of first participant treated, until cut-off date, 02 March 2011

Interventionmonths (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU)12.8

[back to top]

Progression-Free Survival (PFS) Time

The PFS time according to modified WHO criteria as assessed by IRC was defined as duration from first administration of trial treatment until PD (radiological or clinical, if radiological progression is not available) or death due to any cause. Only deaths within 60 days of last tumor assessment are considered. Participants without event are censored on the date of last tumor assessment. (NCT00971932)
Timeframe: Time from first administration of trial treatment to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011

Interventionmonths (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU)4.1

[back to top]

Best Overall Response (BOR) According to Modified World Health Organization (WHO) Criteria

Percentage of participants experiencing a complete response [CR] (complete disappearance of measurable and evaluable disease without new lesions) or partial response [PR] (greater than or equal to 50 percent decrease in the sum of the products of diameters [SOPD] of index lesions compared to the baseline SOPD, with no evidence of PD) confirmed by a subsequent assessment no less than 28 days after criteria for response were first met based on modified WHO criteria as assessed by Independent Review Committee (IRC). (NCT00971932)
Timeframe: Evaluations performed every 6 weeks until progressive disease (PD) reported between day of first participant treated, until cut-off date, 02 March 2011

Interventionpercentage of participants (Number)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU)36.4

[back to top]

Duration of Response

Duration of response according to modified WHO criteria as assessed by IRC was defined as the time from the first assessment of CR or PR until the date of the first occurrence of PD, or until the date of death when death occurred within 60 days of the last tumor assessment or first administration of trial treatment (whichever was last). (NCT00971932)
Timeframe: Time from first assessment of CR or PR to PD, death or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011

Interventionmonths (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU)2.8

[back to top]

Best Overall Response (BOR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

Percentage of participants with objective response based assessment of confirmed CR or confirmed PR according to RECIST as assessed by IRC. CR are those that persist on repeat imaging study at least 28 days after initial documentation of response. PR are those with greater than or equal to 30 percent decrease in the SOPD of index lesions compared to the baseline SOPD, with no evidence of PD. (NCT00971932)
Timeframe: Evaluations performed every 6 weeks until PD reported between day of first participant treated, until cut-off date, 02 March 2011

Interventionpercentage of participants (Number)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU)45.5

[back to top]

Time to Treatment Failure

Time to treatment failure according to modified WHO criteria as assessed by IRC was defined as the time from first administration of trial treatment until the date of the first occurrence of one of the events defining treatment failure: PD assessed by the investigator, discontinuation of treatment due to PD, discontinuation of treatment due to an adverse event (AE), start of any new anticancer therapy, or withdrawal of consent or death within 60 days of the last tumor assessment or first administration of trial treatment. (NCT00971932)
Timeframe: Time from first administration of trial treatment to treatment failure or last tumor assessment, reported between day of first participant treated, until cut-off date, 02 March 2011

Interventionmonths (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil (5-FU)4.2

[back to top]

Overall Survival

Overall survival (defined as the number of days from the day of first treatment to death (from any cause), or until the last day if we know that the patient is alive). (NCT00976456)
Timeframe: 42 months

Interventionmonths (Median)
Bevacizumab + Pemetrexed11.6
Bevacizumab + Pemetrexed + Carboplatin14.4

[back to top]

Progression Free Survival

Progression free survival (defined as the number of days from the day of the first treatment until day of death (from any cause) or progression, whichever occurs earlier, or until the day of the last response assessment, if no progression or death (from any cause) is observed during the study). (NCT00976456)
Timeframe: 42 months

Interventionmonths (Median)
Bevacizumab + Pemetrexed4.8
Bevacizumab + Pemetrexed + Carboplatin6.8

[back to top]

Overall Survival Time

Overall survival time is defined as the time from registration to death due to any cause. The distribution of survival times will be estimated using the method of Kaplan-Meier. (NCT00976573)
Timeframe: up to 5 years

Interventionmonths (Median)
Arm A (Bevacizumab, Paclitaxel, and Carboplatin)14.5
Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus)10.8

[back to top]

Confirmed Tumor Response Rate (Complete Response [CR] or Partial Response [PR]) According to Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

Confirmed Tumor Response: A confirmed tumor response is defined to be a CR or PR (by the RECIST criteria) noted as the objective status on 2 consecutive evaluations at least 8 weeks apart. The proportion of tumor responses will be estimated by the number of confirmed tumor responses divided by the total number of evaluable patients. A ninety percent confidence interval for the true proportion of confirmed tumor responses will be calculated assuming that the number of confirmed tumor responses follows a binomial distribution. (NCT00976573)
Timeframe: Up to 5 years

Interventionpercentage of patients (Number)
Arm A (Bevacizumab, Paclitaxel, and Carboplatin)13
Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus)23

[back to top]

Toxicity

For this secondary endpoint, toxicity is defined as a grade 3 or higher adverse events that is classified as either possibly, probably, or definitely related to study treatment. The assignment of attribution to study treatment and grade (or degree of severity) of the adverse event are classified using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The percentage of participants reporting a grade 3 or higher toxicity is reported. For a list of all reported adverse events, please refer to the Adverse Events Section below. (NCT00976573)
Timeframe: Up to 5 years

,
Interventionpercentage of participants (Number)
NeutropeniaLeukopeniaFatigue
Arm A (Bevacizumab, Paclitaxel, and Carboplatin)351711
Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus)582417

[back to top]

Progression-free Survival

The primary endpoint is progression-free survival (PFS) defined as the time from randomization to documentation of disease progression or death without documentation of progression. The distribution of PFS times will be estimated using the Kaplan-Meier method. Progression is defined using the RECIST Criteria as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum of diameters recorded on study (this includes the baseline sum if that is the smallest on study) or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm of target lesions, or the appearance of one or more new lesions, unequivocal progression of existing non-target lesions, although unequivocal progression should not normally trump target lesion status. It must be representative of overall disease status change, not a single lesion increase. (NCT00976573)
Timeframe: Time from randomization to documentation of disease progression or death without documentation of progression;Up to 5 years

Interventionmonths (Median)
Arm A (Bevacizumab, Paclitaxel, and Carboplatin)5.6
Arm B (Bevacizumab, Paclitaxel, Carboplatin, and Everolimus)5.1

[back to top]

Progression-free Survival (PFS)

Progression-free survival (PFS) is defined to be the time from randomization to progression of disease or death, whichever occurs first. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study, or appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. (NCT00976677)
Timeframe: Every 6 weeks during treatment and every 3 months in follow-up until disease progression or up to 5 years

InterventionMonths (Median)
Arm A4.5
Arm B15.5

[back to top]

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

AEs are any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, or laboratory or physiologic observations occurring in a person given study treatment. The event does not need to be causally related to the study treatment. SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly or birth defect in the offspring of a study subject. (NCT00977561)
Timeframe: Baseline up to follow-up (90 days post dose)

,
Interventionparticipants (Number)
Adverse EventsSerious Adverse Events
Cisplatin or Carboplatin + Etoposide42
Figitumumab + Cisplatin or Carboplatin + Etoposide54

[back to top]

The Median Duration of Overall Survival for Each of the Three Arms.

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. (NCT00977574)
Timeframe: Time from date of study entry to time of death or the date of last contact, assessed up to 5 years

Interventionmonths (Median)
Arm I (Paclitaxel, Carboplatin, Bevacizumab)34
Arm II (Paclitaxel, Carboplatin, Temsirolimus)25
Arm III (Ixabepilone, Carboplatin, Bevacizumab)25.2

[back to top]

The Proportion of Patients With Measurable Disease Who Have Confirmed Objective Tumor Responses by Treatment.

RECIST 1.1 was used to define objective tumor response. A complete response is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. A partial response is defined as At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. There can be no unequivocal progression of non-target lesions and no new lesions. Complete and partial responses are included in the objective tumor response rate. Confirmation of response was not required. (NCT00977574)
Timeframe: Imaging was done every 3 cycles and at any other time clinically indicated. Imaging was required every 9 weeks until progression or initiation on non protocol therapy. After 2 years of protocol therapy or follow up, CT scan or MRI was every 3 months

InterventionParticipants (Count of Participants)
Arm I (Paclitaxel, Carboplatin, Bevacizumab)53
Arm II (Paclitaxel, Carboplatin, Temsirolimus)47
Arm III (Ixabepilone, Carboplatin, Bevacizumab)45

[back to top]

Number of Participants Who Progressed or Died by 25 Months From Enrollment

PFS (Progression free survival) is defined as the duration of time from date of study entry to time of progression or death, whichever occurs first. Patients with a status of alive, progression-free are censored at their date of last follow-up. To lessen the potential for bias in the progression evaluation times between treatment arms and historical controls, progression/death times will be grouped over 6 18-week time intervals. Progressions are carried forward to the end of the interval. All progressions or deaths occurring after the 6th 18-week interval are censored at 25 months for this analysis. Study NCT00977574 (NCT00977574)
Timeframe: at 25 months

InterventionParticipants (Count of Participants)
Arm I (Paclitaxel, Carboplatin, Bevacizumab)86
Arm II (Paclitaxel, Carboplatin, Temsirolimus)96
Arm III (Ixabepilone, Carboplatin, Bevacizumab)88

[back to top]

Frequency and Severity of Toxicity as Assessed by CTCAE v3.0 for Each of the Three Arms.

(NCT00977574)
Timeframe: Median of 10 cycles of treatment plus 30 days

,,
InterventionParticipants (Count of Participants)
Any Adverse Event, Any GradeAny Adverse Event, Grades >= 3Any Adverse Event, Grade 5
Arm I (Paclitaxel, Carboplatin, Bevacizumab)1121054
Arm II (Paclitaxel, Carboplatin, Temsirolimus)1131116
Arm III (Ixabepilone, Carboplatin, Bevacizumab)1141096

[back to top]

Mediastinal Nodal Clearance After Completion of Induction Chemoradiotherapy With or Without Panitumumab.

The assessment of whether mediastinal nodes which were involved at the time of study registration were clear of disease following induction chemoradiotherapy with or without panitumumab; the assessment is made at the time of surgery 4-6 weeks after chemoradiation. If surgery could not be performed, the patient was considered as not having had mediastinal nodal clearance. (NCT00979212)
Timeframe: From date of randomization to time of protocol surgery, approximately 12 weeks.

Interventionpercentage of participants (Number)
Induction CT+RT68.2
Induction CT+RT+Panitumumab48.7

[back to top]

Percentage of Patients With Grade 3 or Higher Acute and Late Adverse Events

Adverse events are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Does not include surgical morbidities. An acute adverse event is defined as any grade 3 or worse toxicity occurring during protocol treatment and within 30 days from the end of protocol treatment that is possibly, probably, or definitely related to treatment. Acute adverse events are any adverse events occurring within 30 days of the end of all protocol treatment. Late adverse events are any adverse events occurring after 30 days after the end of all protocol treatment. (NCT00979212)
Timeframe: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.

,
Interventionpercentage of participants (Number)
AcuteLate
Induction CT+RT81.830.3
Induction CT+RT+Panitumumab69.215.2

[back to top]

Patterns of First Failure

The first failure site will be tabulated, not compared. (NCT00979212)
Timeframe: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study.

,
Interventionparticipants (Number)
Alive, no failureDead, no failureDistant failure onlyLocal and distant failureLocal and regional failureLocal, regional, and distant failureRegional failure only
Induction CT+RT15141001
Induction CT+RT+Panitumumab20392122

[back to top]

Surgical Morbidities in Patients With Resectable Disease at Reassessment

A surgical morbidity is any toxicity occurring within 30 days of protocol surgery, as evaluated using CTCAE v4.0. Rates of grade 3 and higher surgical morbidity were calculated; the rates across arms were not compared. (NCT00979212)
Timeframe: From date of surgery to 30 days following surgery.

Interventionpercentage of patients (Number)
Induction CT+RT42.1
Induction CT+RT+Panitumumab20

[back to top]

Response Rate

Patients are assessed for best response to protocol treatment using the RECIST criteria. The response rate was calculated as the number of patients who have a complete response (CR) or partial response (PR) divided by the total number of analyzable patients at completion of induction chemoradiation +/- panitumumab and prior to anticipated surgery in each arm. Patients without a documented assessment are considered as not having a CR or PR. Rates are not compared across arms. (NCT00979212)
Timeframe: From date of randomization to time of protocol surgery, approximately 12 weeks.

Interventionpercentage of participants (Number)
Induction CT+RT77.3
Induction CT+RT+Panitumumab61.5

[back to top]

Overall Survival

Survival time was calculated from the date of randomization to the date of death from any cause or the date of last follow-up. The Kaplan-Meier method was used to estimate the overall survival rates. One-year survival rates were estimated, not compared. (NCT00979212)
Timeframe: Patients are followed until death. Analysis occurs at time of primary analysis, approximately five years from start of study

Interventionpercentage of participants (Number)
Induction CT+RT94.4
Induction CT+RT+Panitumumab89.1

[back to top]

Overall Survival

Overall survival is defined as time from registration to death from any cause. (NCT00986674)
Timeframe: assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3

Interventionmonths (Median)
Arm I (Carboplatin, Paclitaxel, Cetuximab)9.8
Arm II (Carboplatin, Paclitaxel, Cixutumumab)7.7
Arm III (Carboplatin, Paclitaxel, Cetuximab, Cixutumumab)8.8

[back to top]

Response Rate

Tumor response was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Complete response (CR) was defined disappearance of all tumor lesions. Partial response (PR) was defined as as at least a 30% decrease in the sum of the longest diameters of target lesions, taking as reference the baseline sum longest diameter. Overall response rate= CR+PR. (NCT00986674)
Timeframe: Tumor measurements are repeated every 6 weeks while on treatment. After off treatment, assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3

Interventionpercentage of participants (Number)
Arm I (Carboplatin, Paclitaxel, Cetuximab)11.1
Arm II (Carboplatin, Paclitaxel, Cixutumumab)22.0
Arm III (Carboplatin, Paclitaxel, Cetuximab, Cixutumumab)21.7

[back to top]

Progression Free Survival

"Progression free survival is defined as time from registration to disease progression or death from any cause, whichever occurred earlier. Disease progression was assessed via Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0, and defined as at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, and/or the appearance of one or more new lesion(s), and/or unequivocal progression of existing nontarget lesions .~All eligible and treated patients were included in the analysis." (NCT00986674)
Timeframe: Tumor measurements are repeated every 6 weeks while on treatment. After off treatment, assessed every 3 months if patient is < 2 years from study entry and every 6 months in year 3

Interventionmonths (Median)
Arm I (Carboplatin, Paclitaxel, Cetuximab)3.4
Arm II (Carboplatin, Paclitaxel, Cixutumumab)4.2
Arm III (Carboplatin, Paclitaxel, Cetuximab, Cixutumumab)4.0

[back to top]

Frequency and Severity of Observed Adverse Effects Graded According to NCI CTCAE Version 3.0

(NCT00993616)
Timeframe: Every cycle during treatment and 30 days after the end of treatment

,,,,,
InterventionParticipants (Count of Participants)
LeukopeniaThrombocytopeniaNeutropeniaAnemiaOther hematologicAllergy/immunologyAuditory/earCardiacCoagulationConstitutionalDermatologicEndocrineNauseaVomitingGastrointestinalGenitourinary/renalHemorrhageLymphaticsMetabolicMusculoskeletalNeurosensoryOther neurologicalOcular/visualPainPulmonaryVascular
Grade 012141362623262625102226614102625261725212226152125
Grade 155210100111031149811172531860
Grade 294690210162051700010120402
Grade 312420100010023200020000000
Grade 402200100000000000000000000
Grade 500000000000000001000000000

[back to top]

Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (Version 1.1)

Per Response Evaluation Criteria in Solid Tumors (RECIST) Criteria (version 1.1): Complete Response (CR) is disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm; Partial Response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters; Increasing Disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions); Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest (NCT00993616)
Timeframe: From study entry, up to 5 years

Interventionparticipants (Number)
Complete ResponseIncrease DiseasePartial ResponseStable DiseaseIndeterminate
Treatment181125

[back to top]

Progression Free Survival at 6 Months

Progression is defined according to RECIST v1.0 as at least a 20% increase in the sum of LD target lesions taking as reference the smallest sum LD recorded since study entry, the appearance of one or more new lesions, death due to disease without prior objective documentation of progression, global deterioration in health status attributable to the disease requiring a change in therapy without objective evidence of progression, or unequivocal progression of existing non-target lesions. (NCT00993616)
Timeframe: Every other cycle for 6 months

Interventionpercentage of participants (Number)
Treatment29.6

[back to top]

Overall Survival

Time from the day of randomization to death from any cause. (NCT00993655)
Timeframe: During the study with median follow-up of 33 months

Interventionmonths (Median)
IV Carboplatin + IV Paclitaxel38.1
IP Cisplatin + IV/IP Paclitaxel40.6
IP Carboplatin + IV/IP Paclitaxel59.3

[back to top]

9-month Progression Rate Post-randomization

It is defined as proportion of patients who had progressed at or before 9 months after randomization, i.e., the time from the randomization to the date when the first observation of disease progression (earliest of the date when the first CA 125 meets progression definition and the date of first objective relapse or progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, recorded) has been documented or when death due to any cause has been observed was less than or equal to 9 months. (NCT00993655)
Timeframe: 9 months

InterventionPorportion of participants (Number)
Arm 10.386
Arm 20.347
Arm 30.245

[back to top]

Progression Free Survival

Time from the day of randomization until the time when first observation of disease progression (earliest of the dates of first CA125 which meets progression definition and first objective relapse or progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, has been documented or when death due to any cause has been observed. (NCT00993655)
Timeframe: During the study with median follow-up of 33 months

Interventionmonths (Median)
IV Carboplatin + IV Paclitaxel11.3
IP Cisplatin + IV/IP Paclitaxel12.7
IP Carboplatin + IV/IP Paclitaxel12.5

[back to top]

Progression Free Survival at 6 Months

Percentage of participants who are alive and progression-free at 6 months. (NCT00995007)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Glioblastoma (Combination)1.71
Glioblastoma (Carboplatin Alone)0.89
Anaplastic Astrocytomas (Combination)8.7
Anaplastic Astrocytomas (Carboplatin Alone)17.4

[back to top]

Overall Survival

Time between the first day of treatment and the day of death. (NCT00995007)
Timeframe: Time between the first day of treatment and the day of death, up to 1.5 years

InterventionMonths (Median)
Glioblastoma (Combination)5.58
Glioblastoma (Carboplation Alone)5.22
Anaplastic Astrocytoma (Combination)6.5
Anaplastic Astrocytoma (Carboplatin Alone)9.27

[back to top]

Number of Participants With Adverse Events

Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module. (NCT00995007)
Timeframe: 70 months and 19 days

Interventionparticipants (Number)
Carboplatin55
Vandetanib With Carboplatin56
Cross Over to Vandetanib40

[back to top]

Overall Survival (OS)

Kaplan-Meier method will be used t analyze the time-to-event data including overall survival (OS) and progression-free survival (PFS) (NCT01001910)
Timeframe: First day of treatment on protocol to the date of death, or for living patients the last date of contact, assessed up to 4.5 years

Interventionmonths (Median)
PFSOS
Treatment (Pemetrexed Disodium, Carboplatin)6.850.3

[back to top]

Progression-free Interval

Kaplan-Meier curve will be used to examine all the time-to-event data points in analyzing progression free interval. (NCT01001910)
Timeframe: Time from the first day of treatment to the day that progression is first noted, assessed up to 4.5 years

Interventionmonths (Median)
Treatment (Pemetrexed Disodium, Carboplatin)6.8

[back to top]

Incidence of Toxicities

Secondary outcome included detailed measurement of adverse events from treatment assessed according to National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 3.0. (NCT01001910)
Timeframe: 4.5 years

InterventionFrequency of event (Number)
Hematologic AE Any GradeNon-Hematologic AE Any Grade
Treatment (Pemetrexed Disodium, Carboplatin)24060

[back to top]

CNS Best Response

"CNS best response was defined based on standard criteria. Adding to CR and PR (defined in the primary outcome measure):~CNS stable disease (SD) is achieving all the following:~< 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline~No progression on non-measurable lesions~No new CNS lesions (defined as any new lesion >/= 6 mm in LD)~Stable or decreasing steroid dose~No new/progressive tumor-related neurologic signs or symptoms~No progression of extra-CNS disease as assessed by RECIST~CNS Progressive Disease (PD) was experiencing any of the following:~->/- 40% increase in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline~Progression on non-measurable lesions~New CNS lesions (defined as any new lesion >/= 6 mm in LD)~Increasing steroid dose~New/progressive tumor-related neurologic signs or symptoms~Progression of extra-CNS disease as assessed by RECIST" (NCT01004172)
Timeframe: Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.

InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable Disease >/=24 weeksStable Disease < 24 weeksProgressive Disease
Carboplatin, Bevacizumab, Trastuzumab (if HER2+)024257

[back to top]

Central Nervous System (CNS) Objective Response Rate

"CNS objective response rate is the percentage of participants that achieve CNS complete or partial response as follows:~CNS complete response (CR) is achieved if all of the following are satisfied:~Complete resolution of all measurable (>= 1 cm in longest dimension [LD]) and non-measurable brain metastases~No new CNS lesions (defined as any new lesion >= 6 mm in LD)~Stable or decreasing steroid dose~No new/progressive tumor-related neurologic signs or symptoms~No progression of extra-CNS disease as assessed by RECIST~CNS partial response (PR) is achieved if all of the following are satisfied:~->/= 50% reduction in the volumetric sum of all measurable (>/= 1 cm in LD) brain metastases compared to baseline~No progression on non-measurable lesions~No new CNS lesions (defined as any new lesion >/= 6 mm in LD)~Stable or decreasing steroid dose~No new/progressive tumor-related neurologic signs or symptoms~No progression of extra-CNS disease as assessed by RECIST" (NCT01004172)
Timeframe: Response was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment duration for this study cohort was a median (range) of 8 cycles (1-20) which approximates months given the 4 week cycle length.

Interventionpercentage of participants (Number)
Carboplatin, Bevacizumab, Trastuzumab (if HER2+)63

[back to top]

Overall Survival

Participants were assessed every 6 months post-treatment. Overall survival is defined as the time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods. (NCT01004172)
Timeframe: Maximum survival follow-up for the study cohort was 66 months.

Interventionmonths (Median)
Carboplatin, Bevacizumab, Trastuzumab (if HER2+)14

[back to top]

Progression-Free Survival

"Progression-Free Survival (PFS) is defined as the duration of time from start of treatment to time of disease progression (PD), second cancer, or death, whichever occurs first. PD if any of the following occur:~CNS Disease~>/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment~Progression of non-measurable lesions~New lesions (>/=6 mm)~Non-CNS Disease~• RECIST 1.0 criteria: at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded on treatment or the appearance of >/=1 new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.~Symptomatic~Increasing steroid requirement~Global deterioration of health status requiring discontinuation of treatment~New/progression tumor-related neurologic signs and symptoms except for transient worsening lasting NCT01004172)
Timeframe: Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum PFS follow-up for this study cohort was 18.6 months.

Interventionmonths (Median)
Carboplatin, Bevacizumab, Trastuzumab (if HER2+)5.6

[back to top]

Site of First Progression

"Site of first progression is classified as follows:~CNS Disease~>/=40% increase in the volumetric sum of all measurable lesions as compared to the smallest volume on treatment~Progression of non-measurable lesions~New lesions (>/=6 mm) Non-CNS Disease~Per RECIST 1.0 criteria: PD is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.~Symptomatic~Increasing steroid requirement~Global deterioration of health status requiring discontinuation of treatment~New/progression tumor-related neurologic signs and symptoms (NSS) except for transient worsening lasting NCT01004172)
Timeframe: Disease was evaluated radiologically at baseline, cycle 2, cycle 4 and thereafter on treatment every 2 cycles (CNS disease) and every 4 cycles (non-disease). Maximum progression follow-up for this study cohort was 18.6 months.

Interventionparticipants (Number)
CNSNon-CNSBoth CNS and Non-CNSSymptomaticNo Site
Carboplatin, Bevacizumab, Trastuzumab (if HER2+)1512623

[back to top]

Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 1 Year After Treatment Start

Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE, assigning Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. Adverse events reported as definitely, probably, or possibly related to study treatment. (NCT01005329)
Timeframe: From start of treatment to one year

Interventionpercentage of participants (Number)
Chemoradiation (IMRT), Chemotherapy43.3

[back to top]

Pelvic Failure Rate (Two-year Rate Reported)

Pelvic failure (PF) was defined as disease recurrence in the pelvis, including the pelvic or sacral lymph nodes, and required confirmation by histologic or cytologic biopsy of the recurrent lesion. Death was considered a competing risk. PF rates were estimated using the cumulative incidence method. (NCT01005329)
Timeframe: From registration to two years

Interventionpercentage of participants (Number)
Chemoradiation (IMRT), Chemotherapy0

[back to top]

Overall Survival (Two-year Rate Reported)

Failure was defined as death due to any cause. Patients alive at time of analysis were censored at the date of last contact. Survival rate at two years was estimated using the Kaplan-Meier method. (NCT01005329)
Timeframe: From registration to two years

Interventionpercentage of participants (Number)
Chemoradiation (IMRT), Chemotherapy96.7

[back to top]

Distant Failure (Two-year Rate Reported)

Distant Failure (DF) was defined as the appearance of distant metastasis. Death was considered a competing risk. DF rates were estimated using the cumulative incidence method. (NCT01005329)
Timeframe: From registration to two years

Interventionpercentage of participants (Median)
Chemoradiation (IMRT), Chemotherapy17.0

[back to top]

Disease-free Survival (Two-year Rate Reported)

Failure was defined as pelvic failure (recurrence in the pelvis, which must be confirmed by histologic or cytologic biopsy of the recurrent lesion), distant failure (confirmed by histologic or cytologic biopsy of the recurrent lesion), or death due to any cause. Patients alive at time of analysis were censored at the date of last contact. Disease-free survival rate at two years was estimated using the Kaplan-Meier method. (NCT01005329)
Timeframe: From registration to two years

Interventionpercentage of participants (Number)
Chemoradiation (IMRT), Chemotherapy79.1

[back to top]

Percentage of Participants With Treatment-related, Grade 3+, Non-hematologic Adverse Events Occuring Within 90 Days After Treatment Start

Adverse events are graded using CTCAE v4.0. Grade refers to the severity of the AE, assigning Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. (NCT01005329)
Timeframe: From start of treatment to 90 days

Interventionpercentage of participants (Number)
Chemoradiation (IMRT), Chemotherapy23.3

[back to top]

Progression Free Survival (PFS) of RAD001 in Combination With Weekly Cetuximab and Cisplatin.

Median number of months for which participants are free of progression after initiating treatment with RAD001 in combination with weekly cetuximab and cisplatin. (NCT01009346)
Timeframe: 2 years

Interventionmonths (Median)
Study Arm (RAD001)2.8

[back to top]

Maximum Tolerated Dose (MTD) of RAD001 in Combination With Cetuximab and Cisplatin.

MTD will be defined as a) the dose of RAD001 producing DLT in 0-1 out of 6 patients, or b) the dose level below the dose which produced DLT in <2 out of 6 patients, or c) the dose of 10mg po qd with less than 33% rate of DLT (NCT01009346)
Timeframe: 6 months

Interventionmg (Number)
Study Arm (RAD001, Cetuximab, Cisplatin or Carboplatin)10

[back to top]

Time to Progression

The time from treatment initiation to disease progression or death by any cause. Progression is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01009515)
Timeframe: 2 years

Interventionweeks (Median)
Chemotherapy Combination31

[back to top]

Objective Response Rate (ORR)

Tumor response is evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.0). Target lesions are assessed by physical exam and/or computerized tomography (CT): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient decrease in the sum of the longest diameter of target lesions to qualify for PR nor sufficient increase in the sum of the longest diameter of target lesions to qualify for Progressive Disease; Progressive Disease (PD), 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. The Objective Response Rate (ORR) is the sum of the percentages of patients achieving CR or PR. (NCT01009515)
Timeframe: 6 months

Interventionparticipants (Number)
Complete response (CR)Partial response (PR)Stable diseaseProgressive disease (PD)ORR (CR + PR)
Chemotherapy Combination130124

[back to top]

Safety Profile

All toxicities encountered during the study by patients who receive at least one on-study treatment will be graded according to the NCI CTCAE (Version 3.0). The number of patients experiencing adverse events will be reported according to grade. (NCT01009515)
Timeframe: Up to 30 days after last on-study treatment, for up to 2 years

Interventionparticipants (Number)
Fatigue (Grade 1-2)Fatigue (Grade 3-4)Fever (Grade 1-2)Fever (Grade 3-4)Weight loss (Grade 1-2)Weight loss (Grade 3-4)Anorexia (Grade 1-2)Anorexia (Grade 3-4)Diarrhea (Grade 1-2)Diarrhea (Grade 3-4)Aspartate aminotransferase increased (Grade 1-2)Aspartate aminotransferase increased (Grade 3-4)Vomiting (Grade 1-2)Vomiting (Grade 3-4)Gastrointestinal Bleed (Grade 1-2)Gastrointestinal Bleed (Grade 3-4)Nausea (Grade 1-2)Nausea (Grade 3-4)Alanine aminotransferase increased (Grade 1-2)Alanine aminotransferase increased (Grade 3-4)Hyperbilirubinemia (Grade 1-2)Hyperbilirubinemia (Grade 3-4)Neutropenia (Grade 1-2)Neutropenia (Grade 3-4)Anemia (Grade 1-2)Anemia (Grade 3-4)Lymphopenia (Grade 1-2)Lymphopenia (Grade 3-4)Leukopenia (Grade 1-2)Leukopenia (Grade 3-4)Thrombocytopenia (Grade 1-2)Thrombocytopenia (Grade 3-4)Hyperglycemia (Grade 1-2)Hyperglycemia (Grade 3-4)Hypophosphatemia (Grade 1-2)Hypophosphatemia (Grade 3-4)Hypokalemia (Grade 1-2)Hypokalemia (Grade 3-4)Hyponatremia (Grade 1-2)Hyponatremia (Grade 3-4)Chest wall pain (Grade 1-2)Chest wall pain (Grade 3-4)Bone pain (Grade 1-2)Bone pain (Grade 3-4)Muscle weakness, lower limb (Grade 1-2)Muscle weakness, lower limb (Grade 3-4)Joint pain (Grade 1-2)Joint pain (Grade 3-4)Drowsiness (Grade 1-2)Drowsiness (Grade 3-4)Peripheral Sensory Neuropathy (Grade 1-2)Peripheral Sensory Neutropenia (Grade 3-4)Pericardial effusion (Grade 1-2)Pericardial effusion (Grade 3-4)Edema limbs (Grade 1-2)Edema limbs (Grade 3-4)Alopecia (Grade 1-2)Alopecia (Grade 3-4)Rash (Grade 1-2)Rash (Grade 3-4)Dry mouth (Grade 1-2)Dry mouth (Grade 3-4)
Chemotherapy Combination910101105121210112020103240417030310130301120201001300110804030

[back to top]

Overall Survival

The time from treatment initiation to death by any cause. (NCT01009515)
Timeframe: 2 years

Interventionweeks (Median)
Chemotherapy Combination47

[back to top]

Time to Progression

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01009983)
Timeframe: Approximately 7 months

Interventionmonths (Median)
Arm 15.3

[back to top]

Survival

(NCT01009983)
Timeframe: Approximately 7 months

Interventionmonths (Median)
Arm 16.8

[back to top]

Antitumor Activity as Assessed by Objective Tumor Response According to RECIST Criteria

Complete or Partial response as defined by reduction in tumor size according to RECIST (Response Evaluation Criteria In Solid Tumors) rules. (NCT01009983)
Timeframe: every 28 days for a minimum of 84 days

Interventionparticipants (Number)
Arm 16

[back to top]

Overall Survival (OS)

Overall survival (OS) is defined as the time from randomization until death from any cause. (NCT01014351)
Timeframe: 18 months

InterventionMonths (Median)
Paclitaxel/Carboplatin/Everolimus10.12

[back to top]

Progression-free Survival (PFS)

Progression-free survival (PFS) is defined as the time from randomization until objective tumor progression (PD) or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01014351)
Timeframe: 18 months

InterventionMonths (Median)
Paclitaxel/Carboplatin/Everolimus4.04

[back to top]

Objective Response Rate (ORR)

Objective Response Rate (ORR) is defined as the Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01014351)
Timeframe: 18 months

Interventionpercentage of patients (Number)
Paclitaxel/Carboplatin/Everolimus17

[back to top]

Overall Survival

"Overall survival is defined as time from randomization to date of death (irrespective of reason).~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm." (NCT01015118)
Timeframe: First drug administration to date of death until final DBL 26September16, upto 62 months

InterventionMonths (Median)
Nintedanib62.0
Placebo62.8

[back to top]

Objective Response Based on Investigator Assessment

Objective tumour response defined as either complete response [CR] or partial response [PR] in patients with at least 1 target lesion reported at baseline (NCT01015118)
Timeframe: First drug administration until final DBL 26September16, upto 62 months

Interventionpercentage of participants (Number)
Nintedanib74.3
Placebo70.2

[back to top]

Change in Global Health Status/ Quality of Life (QoL) Scale Over Time.

"Change in Global Health Status/ Quality of life (QoL) over time was calculated on Global Health Status/QoL scale (composite of items 29 and 30 of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 (EORTC QLQ-C30) as a general measure.~As specified in the EORTC scoring manual, for each scale or item, a linear transformation was applied to standardize the raw score to a range from 0 to 100 (high scores represent a high/healthy level of functioning).~Mean presented is Adjusted mean. Adjusted for the stratification factors macroscopic residual postoperative tumour at baseline (yes vs. no), FIGO stage (IIB-III vs IV), and Carboplatin level (AUC5 vs. AUC6)." (NCT01015118)
Timeframe: First drug administration until final DBL 26September16, upto 62 months

Interventionunits on a scale (Mean)
Nintedanib68.79
Placebo70.67

[back to top]

Change in Abdominal/Gastro-intestinal Symptoms Over Time

"Change in abdominal/gastro-intestinal over time was calculated on symptoms (scale composite of items 31 to 37 of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Module for Ovarian Cancer 28 (EORTC QLQ OV-28).~As specified in the EORTC scoring manual, for each scale or item, a linear transformation was applied to standardize the raw score to a range from 0 to 100 (high scores represent a high/severe level of symptomatology).~Mean presented is Adjusted mean. Adjusted for the stratification factors macroscopic residual postoperative tumour at baseline (yes vs. no), FIGO stage (IIB-III vs IV), and Carboplatin level (AUC5 vs. AUC6)." (NCT01015118)
Timeframe: First drug administration until final DBL 26September16, upto 62 months

Interventionunits on a scale (Mean)
Nintedanib24.63
Placebo19.34

[back to top]

Time to CA-125 Tumour Marker Progression

Time to tumour-marker progression was defined as the time from randomisation until the date when Carbohydrate (cancer) antigen (CA-125) values increased to higher than twice the nadir value. CA-125 >=2 x nadir in case nadir value > Upper limit of normal (ULN) or CA-125 >=2 x ULN in case nadir value <= ULN. (NCT01015118)
Timeframe: First drug administration until final DBL 26September16, upto 62 months

InterventionMonths (Median)
Nintedanib16.6
Placebo14.1

[back to top]

PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint).

"Progression free survival is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first based on the Investigator assessment according to Modified Response Evaluation Criteria (mRECIST), version 1.1.~The primary PFS analysis of this trial was performed when approximately 753 patients had experienced a PFS event.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm." (NCT01015118)
Timeframe: First drug administration to date of disease progression or death whichever occurs first , upto 29 months

InterventionMonths (Median)
Nintedanib18.3
Placebo16.6

[back to top]

PFS Based on Investigator Assessment According to mRECIST Version 1.1 (Key Secondary Endpoint - Follow up Analysis).

Follow-up analysis was conducted at the time of overall survival analysis. Progression free survival is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first based on the Investigator assessment according to Modified Response Evaluation Criteria (mRECIST), version 1.1. Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm. (NCT01015118)
Timeframe: First drug administration to date of disease progression or death whichever occurs first until final Data Base Lock (DBL) 26September16, upto 62 months

InterventionMonths (Median)
Nintedanib18.4
Placebo16.6

[back to top]

PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria.

"Progression free survival (PFS) is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first according to the Investigator assessment.~The primary PFS analysis of this trial was performed when approximately 753 patients had experienced a PFS event~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm." (NCT01015118)
Timeframe: First drug administration to date of disease progression or death whichever occurs first , upto 29 months

InterventionMonths (Median)
Nintedanib17.2
Placebo16.6

[back to top]

PFS Based on Investigator Assessment According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST), and Additional Clinical Criteria (Follow up Analysis).

"Follow-up analysis was conducted at the time of overall survival analysis. Progression free survival (PFS) is calculated as the time from randomisation to the date of disease progression, or to the date of death, whichever occurs first according to the Investigator assessment.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve for each treatment arm." (NCT01015118)
Timeframe: First drug administration to date of disease progression or death whichever occurs first until final Data Base Lock (DBL) 26September16, upto 62 months

InterventionMonths (Median)
Nintedanib17.6
Placebo16.6

[back to top]

Number of Participants With Potential Molecular Markers of Resistance to mTOR Inhibition

(NCT01016769)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
PIK3CA MutationAKT3 S472F MutationPTEN R130Q MutationTSC2 MutationTSC1 Mutation
Temsirolimus + Weekly Paclitaxel + Carboplatin41122

[back to top]

Number of Participants Who Experienced Adverse Events

Safety will be assessed in terms of AEs according to CTCAE version 3.0 (NCT01016769)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
Temsirolimus + Weekly Paclitaxel + Carboplatin48

[back to top] [back to top]

Median Overall Survival

(NCT01016769)
Timeframe: 2 years

Interventionmonths (Median)
Temsirolimus + Weekly Paclitaxel + Carboplatin5.9

[back to top]

Overall Survival (OS) During the Maintenance Therapy Period

OS was defined as the duration from the date of the first dose of the maintenance therapy to the date of death from any cause and was calculated by subtracting the induction therapy period from OS. Participants receiving any subsequent systemic anticancer therapy before objective progression or death were censored at date of last objective progression-free disease assessment before starting subsequent systemic anticancer therapy. For participants who were alive, OS was censored at the last contact. (NCT01020786)
Timeframe: From the start of maintenance therapy in Cycle 5 (21-day cycle) until the date of measured progressive disease (PD) or death from any cause (up to 26.3 months)

Interventionmonths (Median)
Overall Survival (OS) at primary endpointOverall Survival (OS) at final endpoint
Pemetrexed + CarboplatinNANA

[back to top]

Progression Free Survival (PFS) During the Maintenance Therapy Period

"Measured from the date of the first dose of the maintenance therapy. Calculated by subtracting induction therapy period from PFS. Tumor response assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0; define when cancer participants improve (respond), stay the same (stabilize), or worsen (progression) during treatments. Participants receiving any subsequent systemic anticancer therapy before objective progression or death were censored at date of last objective progression-free disease assessment before starting subsequent systemic anticancer therapy." (NCT01020786)
Timeframe: From the start of maintenance therapy in Cycle 5 (21-day cycle) until the date of measured progressive disease (PD) or death from any cause (up to 24.4 months)

Interventionmonths (Median)
PFS at primary endpointPFS at final endpoint
Pemetrexed + Carboplatin3.93.9

[back to top]

Percentage of Participants Who Achieved a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Maintenance Therapy Period

"Percentage of participants who achieved confirmed CR (disappearance of all target lesions), PR (30% decrease in sum of longest diameter of target lesions), or SD (small changes that do not meet above criteria). Response derived from target lesion assessments performed before maintenance therapy (as baseline), during maintenance therapy (as post-baseline), and non-target lesion assessments performed during maintenance therapy according to RECIST guideline version 1.0, defines when cancer participants improve (respond), stay the same (stabilize), or worsen (progression) during treatments." (NCT01020786)
Timeframe: From the start of maintenance therapy in Cycle 5 (21-day cycle) until the date of measured progressive disease (PD) or death from any cause (up to 18 months)

Interventionpercentage of participants (Number)
CR+PRCR+PR+SD
Pemetrexed + Carboplatin3.348.3

[back to top]

Percentage of Participants Who Achieved a Complete Response (CR) or Partial Response (PR) During the Induction and Maintenance Therapy Periods

"Calculated as the percentage of participants who achieved a confirmed CR or PR. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve (respond), stay the same (stabilize), or worsen (progression) during treatments. CR = disappearance of all target lesions. PR = 30% decrease in the sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions. Stable Disease (SD) = small changes that do not meet above criteria." (NCT01020786)
Timeframe: Enrollment to date of progressive disease (up to 18 months)

Interventionpercentage of participants (Number)
CRPR
Pemetrexed + Carboplatin0.034.9

[back to top]

Percentage of Participants Who Achieve a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Induction and Maintenance Therapy Periods

"Calculated as the percentage of participants who achieved a confirmed CR, PR, or SD. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve (respond), stay the same (stabilize), or worsen (progression) during treatments. CR = disappearance of all target lesions. PR = 30% decrease in the sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions. SD = small changes that do not meet above criteria." (NCT01020786)
Timeframe: Enrollment to date of progressive disease (up to 18 months)

Interventionpercentage of participants (Number)
CR+PRCR+PR+SD
Pemetrexed + Carboplatin34.972.5

[back to top]

Overall Survival (OS) During the Induction and Maintenance Therapy Periods

OS was defined as the time from the enrollment date to the date of death from any cause. For participants who were alive, OS was censored at the last contact. (NCT01020786)
Timeframe: Enrollment to the date of death from any cause (up to 30.8 months)

Interventionmonths (Median)
Overall Survival (OS) at primary endpointOverall Survival (OS) at final endpoint
Pemetrexed + CarboplatinNA20.2

[back to top]

Progression Free Survival (PFS) During the Induction and Maintenance Therapy Periods

"PFS defined as time from enrollment date to first date of objective progression of disease or of death from any cause. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve (respond), stay the same (stabilize), or worsen (progression) during treatments. Participants receiving any subsequent systemic anticancer therapy before objective progression or death were censored at date of last objective progression-free disease assessment before starting subsequent systemic anticancer therapy." (NCT01020786)
Timeframe: Enrollment to the date of progressive disease (PD) or the date of death from any cause (up to 18 months)

Interventionmonths (Median)
Pemetrexed + Carboplatin5.6

[back to top]

Percentage of Participants Who Observe a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) During the Induction Therapy Period

"Calculated as the percentage of participants who achieved a CR, PR, or SD (confirmed or not). Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve (respond), stay the same (stabilize), or worsen (progression) during treatments. CR = disappearance of all target lesions. PR = 30% decrease in the sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions. SD = small changes that do not meet above criteria." (NCT01020786)
Timeframe: Enrollment to the date of PD, or end of induction period up to Cycle 4 (21-day cycle)

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin81.7

[back to top]

Percentage of Participants Who Achieve a Complete Response (CR) or a Partial Response (PR) During the Induction Therapy Period

"Calculated as percentage of participants who achieved a CR or PR (confirmed or not). Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) guideline version 1.0, which define when cancer participants improve (respond), stay the same (stabilize), or worsen (progression) during treatments. CR = disappearance of all target lesions. PR = 30% decrease in sum of the longest diameter of target lesions. Progressive Disease (PD) = 20% increase in the sum of longest diameter of target lesions. Stable Disease (SD) = small changes that do not meet above criteria." (NCT01020786)
Timeframe: Enrollment to date of PD, or end of induction period up to Cycle 4 (21-day cycle)

Interventionpercentage of participants (Number)
Pemetrexed + Carboplatin38.5

[back to top]

Number of Participants That Achieved Pathologic Complete Response (CR)

Pathologic complete response was defined as absence of invasive carcinoma in the breast, axillary lymph nodes, and skinand absence of tumor emboli within the surgical field. (NCT01036087)
Timeframe: Assessed after 14 weeks (following PNC and FEC preoperative chemotherapy treatment).

InterventionParticipants (Count of Participants)
PNC + FEC11

[back to top] [back to top]

Overall Survival

Overall survival time is defined as the time from randomization to death due to any cause. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT01041781)
Timeframe: Time between randomization and death from any cause, assessed up to 5 years

Interventionmonths (Median)
Arm I (Arm A: Celecoxib + Standard Chemotherapy)11.4
Arm II (Arm B: Placebo + Standard Chemotherapy)12.5

[back to top]

Progression-free Survival

Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT01041781)
Timeframe: Time between randomization and disease relapse or death from any cause, assessed up to 5 years

Interventionmonths (Median)
Arm I (Arm A: Celecoxib + Standard Chemotherapy)5.16
Arm II (Arm B: Placebo + Standard Chemotherapy)5.26

[back to top]

Incidence of Toxicities as Assessed by NCI CTCAE v. 4.0

The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment (NCT01041781)
Timeframe: Up to 5 years

Interventionpercentage of patients (Number)
Arm I (Arm A: Celecoxib + Standard Chemotherapy)61.04
Arm II (Arm B: Placebo + Standard Chemotherapy)55.06

[back to top]

Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the First Quartile (Q1)

Prognostic value of urinary prostaglandin metabolites (PGE-M) levels for worse PFS for patients who had baseline urinary PGE-M above/below the first quartile (Q1, 10.09). Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT01041781)
Timeframe: Up to 5 years

Interventionmonths (Median)
PGE-M < Q17.7
PGE-M >= Q14.9

[back to top]

Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Median Quartile (Q2)

prognostic value of urinary prostaglandin metabolites (PGE-M) levels for worse PFS for patients who had baseline urinary PGE-M above/below the median quartile (Q2, 15.38). Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT01041781)
Timeframe: Up to 5 years

Interventionmonths (Median)
PGE-M < Q26.2
PGE-M >= Q24.2

[back to top]

Prognostic Value of Urinary Prostaglandin Metabolites (PGE-M) Levels for Worse PFS for Patients Who Had Baseline Urinary PGE-M Above/Below the Third Quartile (Q3)

Prognostic value of urinary prostaglandin metabolites (PGE-M) levels for worse PFS for patients who had baseline urinary PGE-M above/below the median quartile (Q3, 27.86). Progression free survival (PFS) is defined as the time from the date of randomization to the date of disease progression or death resulting from any cause, whichever comes first. Progression is defined according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT01041781)
Timeframe: Up to 5 years

Interventionmonths (Median)
PGE-M < Q36.0
PGE-M >= Q33.0

[back to top]

Response Rate

The response rate (percentage) is the percent of patients whose best response was Complete Response (CR) or Partial Response (PR) as defined by RECIST 1.1 criteria. Percentage of successes will be estimated by 100 times the number of successes divided by the total number of evaluable patients. Response rates (including complete and partial response) will be tested using Fisher's exact test (NCT01041781)
Timeframe: Up to 5 years

Interventionpercentage of patients (Number)
Arm I (Arm A: Celecoxib + Standard Chemotherapy)40
Arm II (Arm B: Placebo + Standard Chemotherapy)35

[back to top]

Median Overall Survival (OS)

Defined as the time between Day 1-Cycle 1 to the date of death from any cause. (NCT01042288)
Timeframe: 18 months

Interventionmonths (Median)
Carboplatin/Pemetrexed/Panitumumab17.02

[back to top]

Frequency of Adverse Events and Severity as a Measure of Toxicity

Assessed using NCI CTCAE v4.0 (NCT01042288)
Timeframe: Every 3 weeks (1 cycle) for 6 cycles, then every 7 weeks thereafter

Interventionparticipants (Number)
RashNauseaFatigueHypomagnesemiaNeutrophil Count DecreasedPlatelet Count DecreasedAnemiaMucositisDry SkinAnorexiaDiarrheaConstipationWhite Blood Cell DecreasedPruritusVomitingDehydrationDysgeusiaAlopecia
Carboplatin/Pemetrexed/Panitumumab553933303029282322191917161515131211

[back to top]

Median Time to Progression (TTP)

Defined as the time between Day 1-Cycle 1 and date of first documented disease progression assessed using Response Evaluation Criteria in Solid Tumors (RECISTS) v1.1. (NCT01042288)
Timeframe: 18 months

Interventionmonths (Median)
Carboplatin/Pemetrexed/Panitumumab6.11

[back to top]

Median Progression-free Survival (PFS)

Defined as the time between Day 1-Cycle 1 and date of first documented disease progression or death. (NCT01042288)
Timeframe: Assessments by clinical evaluation, radiographic status, and date of disease progression, estimated 18 months

Interventionmonths (Median)
Carboplatin/Pemetrexed/Panitumumab5.75

[back to top]

Objective Response Rate

(NCT01042288)
Timeframe: Projected 18 months

Interventionpercentage of evaluated participants (Number)
Carboplatin/Pemetrexed/Panitumumab53

[back to top]

Tumor Response Rate

"Proportion of evaluable patients with complete or partial tumor response by RECIST 1.1 criteria.~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (ORR = CR + PR)." (NCT01042522)
Timeframe: Median followup time was 48 months.

Interventionproportion of participants (Number)
Arm I (Paclitaxel, Carboplatin)0.43
Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)0.54

[back to top]

Overall Survival (OS)

The relationship of treatment to overall survival will be assessed. The number of death events in the treatment arm is reported. (NCT01042522)
Timeframe: From start of treatment to time of death or the date of last contact, assessed up to 10 years. Median follow-up time was 48 months.

InterventionParticipants (Count of Participants)
Arm I (Paclitaxel, Carboplatin)5
Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)8

[back to top]

Progression-free Survival (PFS)

The relationship of randomized treatment to progression free survival. The RECIST 1.1 criteria are used for disease progression. This is the criteria: progression is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions). (NCT01042522)
Timeframe: From start of treatment to time of progression or death, whichever occurs first. Median follow-up time was 48 months.

Interventionmonths (Median)
Arm I (Paclitaxel, Carboplatin)27.7
Arm II (Bleomycin Sulfate, Etoposide Phosphate, Cisplatin)19.7

[back to top]

Overall Survival

Overall Survival as measured by the Kaplan-Meier method (NCT01051570)
Timeframe: After treatment, participants will be contacted every 3 months up to 4 years

Interventionmonths (Median)
Carboplatin, RAD 001 & Prednisone12.5

[back to top]

Pharmacokinetics: Observed Carboplatin AUC Was Estimated Based on the Concentration in the 2.75-h Sample.

Using a limited sampling model (i.e., AUC = 0.52 × C2.75h + 0.92) (Sorensen et al., 1993), observed carboplatin AUC was estimated based on the concentration in the 2.75-h sample. (NCT01051570)
Timeframe: Samples were collected Cycle 2, Day 1

Interventionmg/ml*min (Mean)
Carboplatin, RAD 001 & Prednisone5.8

[back to top]

PSA Response Rate

PSA response rate with response defined as => a 30% reduction in PSA (NCT01051570)
Timeframe: Day 1 of each cycle (every 21 days), through study completion, an average of 6 months

Interventionpercentage of participants (Number)
Carboplatin, RAD 001 & Prednisone15

[back to top]

Time to Progression (TTP)

Progression defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions taking as references the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT01051570)
Timeframe: Up to 63 days while on treatment, then up 90 days thereafter. From date of registration to date of progressive disease.

Interventionmonths (Median)
Carboplatin, RAD 001 & Prednisone2.5

[back to top]

Number of Participants With Toxicity as Measured by NCI CTCAE v3.0 Criteria

Number of Participants with Grade 3/4 Toxicity as measured by NCI CTCAE v3.0 criteria (NCT01051570)
Timeframe: Day 1 of each cycle (every 21 days), through study completion, an average of 6 months

InterventionParticipants (Count of Participants)
AnemiaThrombocytopeniaLymphopeniaLeukopeniaInfection without neutropeniaHypophosphatemiaNeutropeniaDehydrationHyperglycemiaHyponatremiaPulmonary embolismFatigueHypercholesterolemiaRashASTHypomagnesemiaHypokalemia
Carboplatin, RAD 001 & Prednisone109644433332211111

[back to top]

Association of PSA Response Rate With Correlative Markers (Phospho mTOR, pAKT, and p70S6)

PSA response defined as a decrease of 30% or more will be tabled against mTOR, pAKT, and p70S6 (1+, 2+, 3+ vs ND) (NCT01051570)
Timeframe: Archival tissue will be collected if available. Optional biopsies pre-treatment and 24 hours after first everolimus and carboplatin dose

Interventionparticipants (Number)
pAKT(ND) vs RespondermTOR(ND) vs Responderp70S6(ND) vs Responder
Carboplatin, RAD 001 & Prednisone101

[back to top]

Total Carboplatin PK: Maximum Observed Plasma Concentration (Cmax)

(NCT01063075)
Timeframe: Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion)

Interventionmicrograms per milliliters (μg/mL) (Geometric Mean)
Cetuximab and Carboplatin (D)11.5

[back to top]

Cetuximab PK: Confirmatory Serum Concentration

(NCT01063075)
Timeframe: Group D: Prior to Carboplatin Infusion, Cycle 1, Day 1

Interventionmicrograms per milliliters (µg/mL) (Geometric Mean)
Cetuximab (D)195

[back to top]

Cetuximab PK: Area Under the Concentration Versus Time Curve During One Dosing Interval at Steady State (AUC τ,ss)

(NCT01063075)
Timeframe: (Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion)

Interventionmicrograms*hour/milliliters (μg•h/mL) (Geometric Mean)
Cetuximab (B and C)17200
Cetuximab and Carboplatin (B and C)16700

[back to top]

Total Carboplatin Pharmacokinetics (PK): Area Under the Concentration (AUC) Versus Time Curve From Time Zero to Infinity (AUC[0-∞])

(NCT01063075)
Timeframe: Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion)

Interventionmicrograms*hour/milliliters (μg•h/mL) (Geometric Mean)
Cetuximab and Carboplatin (D)129

[back to top]

Cetuximab PK: Maximum Observed Plasma Concentration at Steady State (Cmax,ss)

(NCT01063075)
Timeframe: (Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion)

Interventionmicrograms per milliliters (μg/mL) (Geometric Mean)
Cetuximab (B and C)199
Cetuximab and Carboplatin (B and C)199

[back to top]

Total Carboplatin PK: Time of Maximum Observed Plasma Concentration (Tmax)

(NCT01063075)
Timeframe: Group D: Cycle 1, Week 1, Day 1; Prior to Carboplatin Infusion, 1hour (H), 1:30 H, 2 H, 3 H, 5 H, 8 H, 24 H, 72 H (after the Start of Carboplatin Infusion)

InterventionHour (h) (Median)
Cetuximab and Carboplatin (D)1.12

[back to top]

Cetuximab PK: Time of Maximum Observed Plasma Concentration at Steady State (Tmax,ss)

(NCT01063075)
Timeframe: (Group B: Cycle 1 and Cycle 2+ ; Day 1, 8, 15 and Group C: Cycle 1, Day 8, 15 and 22; Cycle 2+, Day 1,8 and 15): Prior to Cetuximab Infusion, 1 Hour (H), 2 H, 4 H, 8 H, 24 H, 72 H, 120 H, and 168 H (after the start of Cetuximab Infusion)

InterventionHour (h) (Median)
Cetuximab (B and C)1.15
Cetuximab and Carboplatin (B and C)3.17

[back to top]

Response Rate

Percentage of patients with a complete or partial response. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01063283)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
Group A3
Group B2

[back to top]

Change in 24 Hour Diastolic Blood Pressure (DBP)

The change for each patient was calculated as mean 24 hour DBP during cycle 2 - mean 24 hour DBP during cycle 1 (NCT01063283)
Timeframe: 2 cycles

InterventionmmHg (Mean)
Group A3
Group B3

[back to top]

Number of Participants With Tumor Response (Complete Response [CR] + Partial Response [PR])

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions (NCT01064479)
Timeframe: 5 years

,
InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseProgressive DiseaseStable DiseaseInevaluable
Arm A (Combination Chemotherapy and Erlotinib Hydrochloride)4278165
Arm B (Combination Chemotherapy and Placebo)51913175

[back to top]

Rash Rates

Participants with a Rash of at least grade 2 within cycle 1. (NCT01064479)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
Arm A (Combination Chemotherapy and Erlotinib Hydrochloride)20
Arm B (Combination Chemotherapy and Placebo)4

[back to top]

Progression Free Survival (PFS)

Kaplan-Meier methods will be used to summarize PFS. In the primary analysis, differences in PFS in Arm A versus Arm B will be tested using a stratified log-rank test with a two-sided alpha of 0.10. Hazard ratios for PFS will be presented using point estimates and 95% confidence intervals. (NCT01064479)
Timeframe: 5 years

Interventionmonths (Median)
Arm A (Combination Chemotherapy and Erlotinib Hydrochloride)6.08
Arm B (Combination Chemotherapy and Placebo)4.4

[back to top]

Overall Survival (OS)

Kaplan-Meier methods will be used to summarize OS. Hazard ratios for OS will be presented using point estimates and 95% confidence intervals. (NCT01064479)
Timeframe: 5 years

Interventionmonths (Median)
Arm A (Combination Chemotherapy and Erlotinib Hydrochloride)16.95
Arm B (Combination Chemotherapy and Placebo)13.67

[back to top]

Disease Control (CR + PR + Stable Disease [SD])

Complete Response (CR) + Partial Response (PR) + Stable disease (NCT01064479)
Timeframe: 5 years

InterventionParticipants (Count of Participants)
Arm A (Combination Chemotherapy and Erlotinib Hydrochloride)47
Arm B (Combination Chemotherapy and Placebo)41

[back to top]

Overall Survival (OS)

OS is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date. (NCT01075100)
Timeframe: 24 months

Interventionmonths (Median)
Triple Negative12.5
HR Positive17.9

[back to top]

Objective Response Rate (ORR)

"Evaluate the objective response rate calculated as CR+ PR in the population evaluable for response, as well as the 2 subgroups (hormone receptor positive [ER+/PR+/HER2-, ER+/PR-/HER2-, ER-/PR+/HER2-]) and ER-/PR-HER2-, separately).~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR." (NCT01075100)
Timeframe: 24 months

Interventionpercentage of participants (Number)
Triple Negative30.4
HR Positive34

[back to top]

Duration of Response

The duration of response is measured from the time measurement criteria are first met for CR/PR until the first date that recurrent or progressive disease is objectively documented. (NCT01075100)
Timeframe: 30 months

Interventionmonths (Median)
Triple Negative6.68
HR Positive5.92

[back to top]

Clinical Benefit Rate (CBR)

Clinical benefit rate (CBR) defined as objective response rate (ORR, CR + PR) + SD >= 6 months (NCT01075100)
Timeframe: 24 months

Interventionpercentage of participants (Number)
Triple Negative41.3
HR Positive56.6

[back to top]

Time to Response

For patients who achieve a major objective response (CR or PR) the time to response will be assessed as the date of registration to the date of response. (NCT01075100)
Timeframe: 24 months

Interventionmonths (Median)
Triple Negative1.27
HR Positive1.60

[back to top]

Progression-free Survival (PFS)

"PFS is measured from the date of randomization to the date of first documented disease progression or date of death, whichever comes first. If a patient neither progresses nor dies, this patient will be censored at last contact date.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions" (NCT01075100)
Timeframe: 24 months

Interventionmonths (Median)
Triple Negative7.6
HR Positive7.6

[back to top]

Toxicity/Safety

Grade 3/4 toxicities (NCT01076504)
Timeframe: 36 months

Interventionparticipants (Number)
AnemiaLeukopeniaThrombocytopeniaNeutropeniaFebrile neutropeniaHypokalemiaFatigueDehydrationInfectionHyponatremiaNauseaVomitingHyperglycemiaMuscle weaknessThrombosis/embolism
Amrubicin/Carboplatin With Pegfilgrastim223036291014118111086343

[back to top]

Time to Progression

Time to progression will be defined as the time from first treatment until objective tumor progression (PD). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01076504)
Timeframe: 36 months

Interventionweeks (Median)
Amrubicin/Carboplatin With Pegfilgrastim23

[back to top]

Objective Response Rate

The Percentage of Patients Who Experience an Objective Benefit From Treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. (NCT01076504)
Timeframe: 36 months

Interventionpercentage of evaluable participants (Number)
Amrubicin/Carboplatin With Pegfilgrastim80

[back to top]

Overall Survival

The Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death (NCT01076504)
Timeframe: 84 months

Interventionmonths (Median)
Amrubicin/Carboplatin With Pegfilgrastim10.3

[back to top]

1-year Survival

Percentage of patients still alive one year after their first treatment (NCT01076504)
Timeframe: 12 months

Interventionpercentage of participants (Number)
Amrubicin/Carboplatin With Pegfilgrastim38

[back to top]

Number of Participants Who Had TEAEs; Data Analysis Cut-Off: January 23, 2013

January 23, 2013 is the date when the first participant in the BI-manufactured cetuximab treatment arm switched to US commercial cetuximab due to changes in the manufacturing process for the BI-manufactured cetuximab necessitating the need to switch participants to US commercial cetuximab. Each participant who switched treatments received at least 2 cycles of BI-manufactured cetuximab before switching. All other components of their treatment regimen remained unchanged. The number of participants who had TEAEs during combination therapy is reported. Using January 23 cut-off, data is un-confounded by lack of BI-manufactured cetuximab. TEAEs were defined as serious and other non-serious adverse events (AEs) that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-in group available in Reported Adverse Event module which is summary of serious and other non-serious AEs regardless of causality. (NCT01081041)
Timeframe: Part 2: Baseline to end of combination therapy or date first participant switched to US commercial cetuximab (up to 18 weeks)

Interventionparticipants (Number)
Part 2: Combination Therapy: Cetuximab (US Commercial)75
Part 2: Combination Therapy: Cetuximab (Manufactured by BI),68

[back to top]

Maximum Serum Concentration (Cmax) of Cetuximab Following 400 mg/m² Cetuximab Dosing

The Cmax of cetuximab following 400 mg/m² cetuximab dosing during Part 2 of the study is reported. As specified in the protocol, pharmacokinetics (PK) samples were not collected during Part 1 of the study, Safety Lead-In or during Part 2 monotherapy. (NCT01081041)
Timeframe: Part 2: Cycle 1, Day 1: 0 hours [(h); immediately postdose], 1 h, 2 h, and 24 h postdose

Interventionmicrograms per milliliter (μg/mL) (Geometric Mean)
Part 2: Combination Therapy: Cetuximab (US Commercial)208
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)208

[back to top]

Number of Participants With Anti-Cetuximab Antibodies

(NCT01081041)
Timeframe: Day 1, Week 1 of Cycles 3 and 5 (postbaseline samples were collected prior to infusion).

Interventionparticipants (Number)
All Participants (Cetuximab)4

[back to top]

Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs); Data Analysis Cut-Off: September 27, 2013

September 27, 2013 is the date when data was last collected for the primary endpoint. Prior to this date, the manufacturing process for the BI-manufactured cetuximab was changed necessitating the need to switch participants to US commercial cetuximab. All other components of their treatment regimen remained unchanged and participants stayed in their original reporting group. Therefore, the number of participants in the BI-manufactured cetuximab treatment arm who had TEAEs includes TEAEs while participants received BI-manufactured and US-commercial cetuximab. Using September 27 cut-off, the analysis of TEAEs is confounded by the switch from BI-manufactured to US commercial cetuximab. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). TEAE information for Safety Lead-In group available in Reported Adverse Events module which is summary of serious and other non-serious AEs regardless of causality. (NCT01081041)
Timeframe: Part 2: Baseline to end of combination therapy (up to 18 weeks)

Interventionparticipants (Number)
Part 2: Combination Therapy: Cetuximab (US Commercial)76
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)68

[back to top]

Cmax of Cetuximab at Steady State

A total of 4 samples were collected at various times during combination therapy, from the third dose of 250 mg/m^2 cetuximab in Cycle 1 (Week 3) through the final dose in Cycle 3 (Week 3) and used to report Cmax of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy. (NCT01081041)
Timeframe: Part 2: Weekly from Cycle 1, Week 3 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose

Interventionmicrograms per milliliter (μg/mL) (Geometric Mean)
Part 2: Combination Therapy: Cetuximab (US Commercial)225
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)199

[back to top]

Progression-Free Survival (PFS)

PFS was defined as duration from the date of randomization to the first date of objective progressive disease (PD) or death from any cause. For each participant who was not known to have died or to have had objective PD as of the 23 October 2014 data cutoff date for the analysis, PFS was censored at the date of the participant's last complete tumor assessment prior to that cutoff date. In addition, any participant in Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Progression of Disease or Death from any Cause (Up to 32.7 Months)

InterventionMonths (Median)
Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU)4.57
Part 2: Combination Therapy: Cetuximab (US Commercial)4.34
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)5.59

[back to top]

Percentage of Participants Having a Confirmed Best Response of Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version [v]1.0) criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Percentage of participants with a confirmed CR or PR=(number of participants whose best overall response was CR or PR)/(number of participants treated)*100. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)

Interventionpercentage of participants (Number)
Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU)24.2
Part 2: Combination Therapy: Cetuximab (US Commercial)32.5
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)36.6

[back to top]

Percentage of Participants Having a Best Response of CR, PR, or Stable Disease (SD) - Disease Control Rate (DCR)

Response was defined using RECIST, v1.0 criteria. CR was defined as the disappearance of all target lesions. PR was defined as having at least a 30% decrease in sum of longest diameter of target lesions. Progressive Disease (PD) was defined as having at least a 20% increase in the sum of the longest diameter of target lesions. Stable Disease (SD) was defined as small changes that did not meet the above criteria. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Progression of Disease (Up to 32.7 Months)

Interventionpercentage of participants (Number)
Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU)69.7
Part 2: Combination Therapy: Cetuximab (US Commercial)58.4
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)62.0

[back to top]

Overall Survival (OS)

OS was defined as duration from the date of randomization to the date of death from any cause. For each participant not known to have died as of the 23 October 2014 data cutoff date for the analysis, OS was censored at the date last known to be alive. In addition, any participants on Arm B who was switched from BI-manufactured cetuximab to ImClone-manufactured cetuximab was censored at the time of the switch. (NCT01081041)
Timeframe: Parts 1 and 2: Randomization to Date of Death from any Cause (Up to 36.3 Months)

InterventionMonths (Median)
Part 1: Safety Lead-In (Cetuximab, Cis or Carbo, 5-FU)9.13
Part 2: Combination Therapy: Cetuximab (US Commercial)9.23
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)9.46

[back to top]

Area Under the Concentration Curve (AUC) of Cetuximab at Steady State

A total of 4 samples were collected during combination therapy, from the first dose of 250 mg/m^2 cetuximab in Cycle 1 (Day 1) through the final dose in Cycle 3 (Week 3) and used to report AUC of cetuximab at steady state during Part 2 of the study. As specified in the protocol, PK samples were not collected during Part 1 of the study, Safety Lead-In, or during Part 2 monotherapy. (NCT01081041)
Timeframe: Part 2: Weekly from Cycle 1, Day 1 through Cycle 3, Week 3: 0 h (immediately postdose), 24 h, 96 h, and 168 h postdose

Interventionmicrograms*hours/milliliter (μg*h/mL) (Geometric Mean)
Part 2: Combination Therapy: Cetuximab (US Commercial)21900
Part 2: Combination Therapy: Cetuximab (Manufactured by BI)18800

[back to top]

Patient Reported Quality of Life

Patient reported quality of life was measured with the Treatment Outcome Index of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). Each item in the FACT-O TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements (or questions), reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. The FACT-O TOI score ranges 0-100 with a large score suggests better QOL (NCT01081262)
Timeframe: baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5

,
Interventionunits on a scale (Mean)
Baseline (pre-treatment)Pre-Cycle 4Post-Cycle 6Six Months Post-ChemoEnd of Bevacizumab (BEV)Six Months after BEV2 Years after BEV3 Years after BEV
Arm I (Carboplatin and Paclitaxel)62.657.565.274.168.954.071.776.4
Arm IV (Oxaliplatin, Capecitabine, Bevacizumab)75.476.071.868.749.970.577.076.0

[back to top]

Patient Reported Neurotoxicity

Patient reported neurotoxicity symptoms as measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less neurotoxicity. (NCT01081262)
Timeframe: baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5

,
Interventionunits on a scale. (Mean)
Baseline (pre-treatment)Pre-cycle 4Post cycle 6Six months post chemoEnd of bevacizumab (BEV)Six months after BEV2 years after BEV3 years after BEV
Arm I (Carboplatin and Paclitaxel)16.07.36.55.016.010.08.014.0
Arm IV (Oxaliplatin, Capecitabine, Bevacizumab)16.05.78.010.711.77.016.016.0

[back to top]

Patient Reported Neurotoxicity

Patient reported neurotoxicity symptoms as measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less neurotoxicity. (NCT01081262)
Timeframe: baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5

Interventionunits on a scale. (Mean)
Baseline (pre-treatment)Pre-cycle 4Post cycle 6End of bevacizumab (BEV)Six months after BEV2 years after BEV
Arm II (Oxaliplatin and Capecitabine)15.311.811.710.010.014.0

[back to top]

Patient Reported Quality of Life

Patient reported quality of life was measured with the Treatment Outcome Index of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). Each item in the FACT-O TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements (or questions), reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. The FACT-O TOI score ranges 0-100 with a large score suggests better QOL (NCT01081262)
Timeframe: baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5

Interventionunits on a scale (Mean)
Baseline (pre-treatment)Pre-Cycle 4Post-Cycle 6End of Bevacizumab (BEV)Six Months after BEV2 Years after BEV
Arm II (Oxaliplatin and Capecitabine)62.372.973.553.353.056.0

[back to top]

Overall Survival

Overall survival is defined as the duration of time from study entry to time of death, or the date of last contact. (NCT01081262)
Timeframe: Up to five years

Interventionmonths (Median)
Arm I (Carboplatin and Paclitaxel)37.6
Arm II (Oxaliplatin and Capecitabine)27.8
Arm III (Carboplatin, Paclitaxel, Bevacizumab)27.7
Arm IV (Oxaliplatin, Capecitabine, Bevacizumab)55.7

[back to top]

Progression-free Survival

Progression is defined using Response Evaluation Criteria in Solid Tumors criteria (RECIST v1.0) as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01081262)
Timeframe: Is measured from date of randomization until first indication of progression based on RECIST criteria or death from any cause, or if progression-free at last contact, the date of last disease assessment up to 10 years.

InterventionMonths (Median)
Arm I (Carboplatin and Paclitaxel)36.1
Arm II (Oxaliplatin and Capecitabine)7.4
Arm III (Carboplatin, Paclitaxel, Bevacizumab)15.4
Arm IV (Oxaliplatin, Capecitabine, Bevacizumab)23.3

[back to top]

Participants With Grade 1 or Higher Non-serious Adverse Effects Assessed by CTCAE Version 4.0

Grade 1 or higher non-serious adverse events were graded by CTC AE v 4. (NCT01081262)
Timeframe: Every cycle while on treatment, up to 5 years

,,,
InterventionParticipants (Count of Participants)
Abnormal lab valuesAllergic reactionAllergic rhinitisAlopeciaAnemiaBleedingCold-like symptomsConstipationDiarrheadyspneaEdema LimbsFatigueFeverHand/Foot SyndromeHeadacheHypertensionHypomagnesemiaInfectionLaryngeal SpasmLow LymphocytesLow MoodLow NeutrophilsLow plateletsLow white Blood CellsMucositisNausea/VomitingOral ProblemsOtherOther GI ProblemsPainPeripheral/Sensory NeuropathyPneumothoraxRaised CA19-9Raised Blood CountsRashStomatitisTaste AlterationUrinary ProblemsVaginal BleedingWeight GainWeight Loss
Arm I (Carboplatin and Paclitaxel)830111212352010313314011785183489110014031002
Arm II (Oxaliplatin and Capecitabine)10111713461110004800412535182466111012220113
Arm III (Carboplatin, Paclitaxel, Bevacizumab)100194377530820592302145419477780203111114
Arm IV (Oxaliplatin, Capecitabine, Bevacizumab)104156569800111741003001776399767100014022225

[back to top]

Patient Reported Neurotoxicity

Patient reported neurotoxicity symptoms as measured with the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - neurotoxicity subscale (short version) (FACT/GOG-Ntx subscale). The FACT/GOG-Ntx subscale contains 4 items. Each item was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative items, reversal was performed prior to score calculation. According to the FACIT measurement system, the Ntx score was the summation of the individual item scores if more than 50% of subscale items were answered. When unanswered items existed, a subscale score was prorated by multiplying the mean of the answered item scores by the number of items in the scale. The Ntx score ranges 0-16 with a large score suggests less neurotoxicity. (NCT01081262)
Timeframe: baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5

Interventionunits on a scale. (Mean)
Baseline (pre-treatment)Pre-cycle 4Post cycle 6Six months post chemoEnd of bevacizumab (BEV)Six months after BEV2 years after BEV3 years after BEV4 years after BEV5 years after BEV
Arm III (Carboplatin, Paclitaxel, Bevacizumab)14.312.711.011.39.59.05.59.56.57.5

[back to top]

Objective Tumor Response

Complete and Partial Tumor Response by RECIST 1.1. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v.1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR),.>=30% decrease in the sum of the longest diameter of target lesions; Overall response (OR) = CR + PR (NCT01081262)
Timeframe: CT scan or MRI if used to follow lesion for measurable disease every other cycle for the first 6 months; then every 3 months x 2; then every 6 months thereafter until disease progression, and any other time clinically indicated, up to 5 years

InterventionPercentage of Participants (Number)
Arm I (Carboplatin and Paclitaxel)22
Arm II (Oxaliplatin and Capecitabine)27
Arm III (Carboplatin, Paclitaxel, Bevacizumab)43
Arm IV (Oxaliplatin, Capecitabine, Bevacizumab)40

[back to top]

Patient Reported Quality of Life

Patient reported quality of life was measured with the Treatment Outcome Index of the Functional Assessment of Cancer Therapy for endometrial cancer (FACT-O TOI). The FACT-O TOI is a scale for assessing general QOL of ovarian cancer patients. It consists of three subscales: Physical Well Being (7 items), Functional Well Being (7 items), and Ovarian Cancer subscale (11 items). Each item in the FACT-O TOI was scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). For the negative statements (or questions), reversal was performed prior to score calculation. According to the FACIT measurement system, a subscale score was the summation of the individual item scores if more than 50% of subscale items were answered. The FACT-O TOI score ranges 0-100 with a large score suggests better QOL (NCT01081262)
Timeframe: baseline (pre-treatment), pre cycle 4, post cycle 6, six months post-chemo, end of bevacizumab [BEV] (or 39 weeks after completion of chemotherapy in the non-BEV arms or in those who discontinue BEV), six months after BEV, and years 2, 3, 4, and 5

Interventionunits on a scale (Mean)
Baseline (pre-treatment)Pre-Cycle 4Post-Cycle 6Six Months Post-ChemoEnd of Bevacizumab (BEV)Six Months after BEV2 Years after BEV3 Years after BEV4 Years after BEV5 Years after BEV
Arm III (Carboplatin, Paclitaxel, Bevacizumab)68.768.768.380.373.087.576.380.571.578.0

[back to top]

Overall Survival (OS)

OS was defined as the time from randomisation until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive. (NCT01081951)
Timeframe: Following disease progression, patients will be contacted every 12 weeks to assess survival status until the final analysis (approximately 50 months)

InterventionParticipants (Number of deaths) (Number)
Olaparib/Carboplatin AUC4/Paclitaxel54
Carboplatin AUC6/Paclitaxel47

[back to top]

Percentage Change in Tumour Size

The total tumour size was defined as the sum of the longest diameters of the target lesions. At week 9, the percentage change in tumour size was calculated as [(week 9 sum of target lesions - baseline sum of target lesions)/baseline sum of target lesions]*100 for each patient. Imputations were used for missing data where possible. (NCT01081951)
Timeframe: Week 9 (+/- 1 week)

InterventionPercentage change (Least Squares Mean)
Olaparib/Carboplatin AUC4/Paclitaxel-38.4
Carboplatin AUC6/Paclitaxel-39.1

[back to top]

Progression Free Survival (PFS)

PFS (based on independent central review) was defined as the time from randomisation until objective disease progression as defined by Response Evaluation Criteria In Solid Tumours (RECIST) v1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). (NCT01081951)
Timeframe: Radiologic scans performed at weeks 9 and 18 (+/-1 week) and every 12 weeks thereafter relative to the date of randomisation until the primary analysis (approximately 20 months)

Interventionmonths (Median)
Olaparib/Carboplatin AUC4/Paclitaxel12.2
Carboplatin AUC6/Paclitaxel9.6

[back to top]

Overall Survival (OS)

OS is defined as the duration from the date of enrollment to the date of death from any cause. For participants who were alive at the time of the data inclusion cutoff, OS was censored at the date of last contact prior to that cut-off date. (NCT01087970)
Timeframe: From enrollment to the date of death from any cause up to 26.4 months (assessment completed during trial period at least every 3 months)

Interventionmonths (Median)
Cetuximab + Pemetrexed + Carboplatin/Cisplatin11.1

[back to top]

Percentage of Participants Having a Confirmed Partial Response (PR) or Complete Response (CR)

PR or CR is classified by the investigators according to RECIST criteria version 1.0. PR is a ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesions; CR is the disappearance of all target and non-target lesions. Percentage of participants having a PR or CR is calculated as a total number of participants with PR or CR from enrollment until disease progression or recurrence divided by the total number of participants treated, then multiplied by 100. (NCT01087970)
Timeframe: From enrollment to objectively determined progressive disease up to 15.3 months (tumor assessments performed every other cycle during study treatment until progressive disease)

Interventionpercentage of participants (Number)
Cetuximab + Pemetrexed + Carboplatin/Cisplatin25.9

[back to top]

Number of Participants Who Died While on Treatment and Died During 30-Day Post-Treatment Discontinuation Follow-Up (FU)

Presented are the number of participants who died due to adverse events (AEs) while on treatment and participants who died due to progressive disease (PD) during the 30-day post-treatment discontinuation FU. (NCT01087970)
Timeframe: From enrollment to 30 days post-treatment discontinuation up to 26.4 months

Interventionparticipants (Number)
Due to AE while on treatmentDue to PD during 30-day FU
Cetuximab + Pemetrexed + Carboplatin/Cisplatin35

[back to top]

Change From Baseline in Participant-Reported European-Quality of Life-5 Dimension Instrument-3 Levels (EQ-5D-3L)

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems/some or moderate problems/extreme problems) within a particular EQ-5D dimension. A regression equation defines a utility value for these health states to generate an index score. The possible values for index score range from -0.594 (severe problems in all 5 dimensions) to 1 (no problem in all dimensions) on a scale where 1 represents the best possible health state. The EQ-5D Visual Analog Scale (VAS) is used to record a participant's rating for his/her current health-related quality of life state on the day of questionnaire administration and is captured on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state). (NCT01087970)
Timeframe: Baseline, Day 1 of Cycles 2, 4, 6, cetuximab monotherapy Cycles 2 and 4 (21-day cycle)

Interventionunits on a scale (Mean)
Change in Index Score at Cycle 2 (n=43)Change in Index Score at Cycle 4 (n=29)Change in Index Score at Cycle 6 (n=24)Change in Index Score at monotherapy Cycle2 (n=14)Change in Index Score at monotherapy Cycle 4 (n=7)Change in VAS Score at Cycle 2 (n=41)Change in VAS Score at Cycle 4 (n=28)Change in VAS Score at Cycle 6 (n=21)Change in VAS Score at monotherapy Cycle 2 (n=14)Change in VAS Score at monotherapy Cycle 4 (n=7)
Cetuximab + Pemetrexed + Carboplatin/Cisplatin0.0380.070-0.0630.0160.0593.8542.1070.333-1.5000.571

[back to top]

Progression-Free Survival (PFS)

PFS was defined as the duration from the date of enrollment to the first date of documented objective progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions or the appearance of new lesions. For participants who were not known to have died or to have had objective PD at the time of the data inclusion cutoff, PFS was censored at their last objective progression-free disease assessment prior to the cutoff date or the date of initiation of subsequent systemic anticancer therapy. (NCT01087970)
Timeframe: From enrollment to measured progressive disease up to 15.3 months (tumor assessments performed every other cycle during study treatment, and then every 6 weeks during follow-up)

Interventionmonths (Median)
Cetuximab + Pemetrexed + Carboplatin/Cisplatin5.1

[back to top]

Change From Baseline in Performance Status Scale for Head and Neck Cancer (PSS-HNC)

PSS-HNC is a clinician-rated instrument designed to measure speaking and eating disabilities of participants with head and neck cancer and consists of 3 subscales: normalcy of diet (NOD) subscale measures the ability of the participants to eat a normal diet, subscale ranges from 0 (non-oral feeding) to 100 (unrestricted diet); understandability of speech (UOS) subscale measures the degree a clinician is able to understand the participant's speech, subscale ranges from 0 (never understandable) to 100 (always understandable); eating in public (EIP) subscale, rating based on the participant's response to the questions of whom he/she eats with and in what setting, subscale ranges from 0 (always eats alone) to 100 (no restriction of place, food, or companion). Change from baseline: negative value represents a decrease in function and a positive value represents an increase in function. (NCT01087970)
Timeframe: Baseline, Day 1 of Cycles 2, 4, 6, cetuximab monotherapy Cycles 2 and 4 (21-day cycle)

Interventionunits on a scale (Mean)
Change in NOD at Cycle 2 (n=52)Change in UOS at Cycle 2 (n=52)change in EIP at Cycle 2 (n=52)Change in NOD at Cycle 4 (n=34)Change in UOS at Cycle 4 (n=35)Change in EIP at Cycle 4 (n=34)Change in NOD at Cycle 6 (n=28)Change in UOS at Cycle 6 (n=28)Change in EIP at Cycle 6 (n=28)Change in NOD at monotherapy Cycle 2 (n=16)Change in UOS at monotherapy Cycle 2 (n=16)Change in EIP at monotherapy Cycle 2 (n=17)Change in NOD at monotherapy Cycle 4 (n=9)Change in UOS at monotherapy Cycle 4 (n=9)Change in EIP at monotherapy Cycle 4 (n=9)
Cetuximab + Pemetrexed + Carboplatin/Cisplatin4.62-2.402.883.24-0.71-6.629.29-1.79-1.7911.88-4.69-4.418.892.782.78

[back to top]

Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: Xerostomia Questionnaire (XQ)

"Determine quality of life of surviving patients measured by patient reported outcomes:~XQ measures severity of radiation-induced xerostomia and patient reported quality of life. 8 question total:4 on dryness while eating/chewing, 4 on dryness when not eating/chewing. 0-10 (higher scores=severe dryness/discomfort). Composite Scores range from 0 (no xerostomia) -100 (highest level of xerostomia)." (NCT01088802)
Timeframe: Baseline, 6-8 weeks, 1 year, 2 years, 3 years, 4-5 year visit

Interventionscore on a scale (Mean)
baseline6-8 week visit1 year visit2 year visit3 year visit4-5 year visit
Dose De-escalating Radiation Therapy With Chemotherapy0.656.233.272.962.872.67

[back to top]

Percentage of Patients Free of Grade 3+ Late Toxicity

The goal is to achieve a prevalence of < 15% grade 3+ late toxicity at 2 years; reported as percentage of patients who were free of grade 3+ adverse events (AEs) as measured by Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0) between 6 months and 24 months. The outcome is reported as percentage of patients who were free of grade 3+ adverse events. (NCT01088802)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Dose De-escalating Radiation Therapy With Chemotherapy86

[back to top]

Percentage of Patients With Locoregional Tumor Control

Locoregional tumor control > 85 + or - 7% at 2 years; measured through progression-free survival (the time from assignment in a clinical trial to disease progression or death from any cause). Locoregional tumor control is reported as percentage of patients meeting this criteria. (NCT01088802)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Dose De-escalating Radiation Therapy With Chemotherapy92

[back to top]

Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: M.D. Anderson Dysphagia Inventory (MDADI)

"Determine quality of life of surviving patients measured by patient reported outcomes:~-MDADI-Self-administered assessment on patient swallowing ability. There are 19 questions specific to swallowing that study patients completed. Composite score is the average of the 19 questions. The scale is 20 (extremely low functioning) to 100 (high functioning).~Composite score is reported." (NCT01088802)
Timeframe: Baseline, 6-8 weeks, 6 months, 1 year, 2 years, 3 years, 4-5 year visit

Interventionscore on a scale (Mean)
Baseline6-8 week visit6 month visit1 year visit2 year visit3 year visit4-5 year visit
Dose De-escalating Radiation Therapy With Chemotherapy87.7177.7578.6286.1887.6488.1689.48

[back to top]

Quality of Life Measured Through Patient-reported Outcome Measures on Assessments: MD Anderson Symptom Inventory-head and Neck Cancer (MDASI-HN)

"Determine quality of life of surviving patients measured by patient reported outcomes:~MDASI-HN-Self-reported assessment. Measures symptom severity in previous day. Study patients answered 9 specific questions specific to head and neck cancer. Symptom severity scores, from 0 (not present) to 10 (worst possible). Composite score calculated average of individual scores.~Mean module (head and neck) symptom severity is reported." (NCT01088802)
Timeframe: Baseline, 6-8 weeks, 1 year, 2 years, 3 years, 4-5 year visit

Interventionscore on a scale (Mean)
baseline6-8 week visit1 year visit2 year visit3 year visit4-5 year visit
Dose De-escalating Radiation Therapy With Chemotherapy0.454.171.060.980.920.9

[back to top]

EFS of Children With Incompletely Resected Ependymoma Who Are Unable to Achieve a Complete Response (CR) by Post-operative Induction Chemotherapy or by Second Surgery and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy

The Kaplan-Meier estimate of EFS is calculated from enrollment date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of EFS are presented.

Interventionpercentage of participants (Number)
Arm IV: Nonrandomly Assigned to Arm II Treatment33.6

[back to top]

EFS of Children With Supratentorial Classic Ependymoma Who Achieve Complete Resection at First or Second Surgery or Children Who Achieve Complete Response (CR) After Induction Chemo and Who Are Non-randomly Assigned to Observation

The Kaplan-Meier estimate of EFS is calculated from enrollment date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of EFS are presented.

Interventionpercentage of participants (Number)
Arm I: Observation66.9

[back to top]

EFS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only

Kaplan-Meier estimates of EFS are calculated from randomization date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of EFS are presented.

Interventionpercentage of participants (Number)
Arm II: Randomized to Radiation With Maintenance Chemotherapy in Stratum 172.7
Arm III: Randomized to Radiation Only in Stratum 162.9

[back to top]

Overall Survival (OS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only

Kaplan-Meier estimates of OS are calculated from randomization date to death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) is conveyed by the hazard ratio and 90.46% stagewise adjusted Wald confidence interval. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of OS are presented.

Interventionpercentage of participants (Number)
Arm II: Randomized to Radiation With Maintenance Chemotherapy88.3
Arm III: Randomized to Radiation Only86.9

[back to top]

OS of Children With Supratentorial Classic Ependymoma Who Achieve Complete Resection at First or Second Surgery or Children Who Achieve Complete Response (CR) After Induction Chemo and Who Are Non-randomly Assigned to Observation

The Kaplan-Meier estimate of OS is calculated from enrollment date to death from any cause. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of OS are presented.

Interventionpercentage of participants (Number)
Arm I: Observation100

[back to top]

OS of Children With Incompletely Resected Ependymoma Who Are Unable to Achieve a Complete Response (CR) by Post-operative Induction Chemotherapy or by Second Surgery and Who Are Non-randomly Assigned to Receive Maintenance Chemotherapy

The Kaplan-Meier estimate of OS is calculated from enrollment date to death from any cause. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of OS are presented.

Interventionpercentage of participants (Number)
Arm IV: Nonrandomly Assigned to Arm II Treatment74.0

[back to top]

OS in Children With Incomplete Resection After Initial Surgery Who Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only

Kaplan-Meier estimates of OS are calculated from randomization date to death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of OS are presented.

Interventionpercentage of participants (Number)
Arm II: Randomized to Radiation With Maintenance Chemotherapy in Stratum 269.2
Arm III: Randomized to Radiation Only in Stratum 289.5

[back to top]

OS in Children Who Have Completely Resected Ependymoma at Initial Surgery and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only.

Kaplan-Meier estimates of OS are calculated from randomization date to death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of OS are presented.

Interventionpercentage of participants (Number)
Arm II: Randomized to Radiation With Maintenance Chemotherapy in Stratum 190.7
Arm III: Randomized to Radiation Only in Stratum 186.4

[back to top]

Event-free Survival (EFS) in Children Who Have Completely Resected Ependymoma or Achieved CR and Are Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only

Kaplan-Meier estimates of EFS are calculated from randomization date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) is conveyed by the hazard ratio and 90.46% stagewise adjusted Wald confidence interval. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of EFS are presented

Interventionpercentage of participants (Number)
Arm II: Randomized to Radiation With Maintenance Chemotherapy69.2
Arm III: Randomized to Radiation Only63.7

[back to top]

EFS With Incomplete Resection After Initial Surgery, Then Achieved CR After Induction Chemotherapy or GTR/NTR After Second Surgery and Treated With Post-radiation Maintenance Chemotherapy or Post-radiation Observation Only

Kaplan-Meier estimates of EFS are calculated from randomization date to first occurrence of disease progression, disease recurrence, second malignant neoplasm, or death from any cause. The comparison between randomized arms (post-radiation maintenance chemotherapy versus post-radiation observation only) for this stratum is conveyed by the hazard ratio and 95% Wald confidence interval. (NCT01096368)
Timeframe: Up to 10 years after enrollment. 5-year estimates of EFS are presented.

Interventionpercentage of participants (Number)
Arm II: Randomized to Radiation With Maintenance Chemotherapy in Stratum 241.7
Arm III: Randomized to Radiation Only in Stratum 267.5

[back to top]

Number of Participants Requiring One or Two Apheresis Collection Days to Reach ≥5 x 10^6 CD34 Cells/kg

Number of participants requiring one or two apheresis collection days to reach collection goal. (NCT01097057)
Timeframe: Up to Four Apheresis Days

InterventionParticipants (Count of Participants)
One apheresis collection dayTwo apheresis collection daysThree apheresis collection daysFour apheresis collection days
Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)15200

[back to top]

Total Number of Participants Who Did Not Collect ≥5 x 10^6 CD34 Cells/kg in a Maximum of Four Apheresis Days

Number of participants who did not collect ≥5 x 10^6 CD34 cells/kg in up to four apheresis days (NCT01097057)
Timeframe: Up to Four Apheresis Days

InterventionParticipants (Count of Participants)
Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)0

[back to top]

Number of Patients Who Achieved ≥5 x 10^6 CD34 Cells/kg in ≤4 Apheresis Days

Number of patients to collect at least 5 x 10^6 CD34 cells/kg in under 4 apheresis procedures. (NCT01097057)
Timeframe: Up to Four Apheresis Days

InterventionParticipants (Count of Participants)
Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)17

[back to top]

Number of Patients to Mobilize ≥5 x 10^6 CD34 Cells/kg Autologous PBSC (Efficacy)

Number of patients who achieved ≥5 x 10^6 CD34 cells/kg autologous PBSC collection by apheresis. (NCT01097057)
Timeframe: One Month

InterventionParticipants (Count of Participants)
Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)17

[back to top]

Progression-free Survival of Optimal (RO) 1 cm

Progression-Free Survival is the period from study entry until disease progression, death or date of last contact. Disease progression defined by imaging or palpation of at least a 20% increase in the sum of the LD of target lesions, the appearance of one or more new lesions, or unequivocal progression of existing nontarget lesions, the date of progression will be defined as the date such lesions were first found to be progressed by imaging or palpation. Estimated the PFS with the Kaplan-Meier product-limit estimator stratified by debulking status (optimal, sub-optimal).The Cox proportional hazards regression model to assess the association of gene expression and cytokines with PFS. (NCT01097746)
Timeframe: 2 years

InterventionNumber of months (Median)
Optimal (no residual)Optimal (<1 cm)Suboptimal (>1 cm)
Treatment (Paclitaxel, Carboplatin, Bevacizumab)22.416.916.9

[back to top]

Number of Participants With Treatment Success

Participants with newly diagnosed ovarian, primary peritoneal, and fallopian tube cancers treated with bevacizumab, carboplatin, and weekly paclitaxel that can tolerate at least 4 cycles of therapy regardless of delay or dose modification. (NCT01097746)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Treatment (Paclitaxel, Carboplatin, Bevacizumab)23

[back to top]

Number of Participants With Adverse Events

Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module. (NCT01100931)
Timeframe: 31.5 months

InterventionParticipants (Number)
Phase I22
Phase II19

[back to top]

Phase 2 Objective Response Rate (Partial Response (PR) + Complete Response (CR)).

Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. (NCT01100931)
Timeframe: up to 18 weeks

InterventionParticipants (Number)
Complete ResponsePartial Response
Phase II02

[back to top]

Phase 1 Safe and Tolerable Phase 2 Dose.

"Phase I: Doses were given at different dose levels until the maximum tolerated dose (MTD) was reached. Dose level 1: 3.6 mg/m^2, dose level 2:5 mg/m^2 , dose level 3:6 mg/m^2, dose level 4:8 mg/m^2, dose level 5:10 mg/m^2 (MTD), dose level 6:12 mg/m^2. Doses were given by continuous intravenous infusion over 72 hours every 21 days.Three patients were enrolled at each dose level in the absence of dose limiting toxicity (DLT). A DLT is defined as adverse events occurring during the first cycle of therapy (e.g. every 21 days).~Phase 2 dose is based upon dose limiting toxicities experienced during cycle 1." (NCT01100931)
Timeframe: 1 year

Interventionmg/m^2 (Number)
Phase I10

[back to top]

Response Rate

"Response is evaluated based on RECIST criteria v1.1 and defined as either complete response or partial response. Complete response is defined as disappearance of all lesions. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the current step's baseline sum diameters.~The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis." (NCT01107626)
Timeframe: Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

Interventionproportion of participants (Number)
Arm A (Induction Then Maintenance With Bevacizumab)0.125
Arm B (Induction Then Maintenance With Pemetrexed0.187
Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)0.212

[back to top]

Progression-free Survival

"Progression-free survival is defined as the time from randomization to progression or death, whichever occurs first. Progression is evaluated based on RECIST criteria and defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on current step. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.~The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis." (NCT01107626)
Timeframe: Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

Interventionmonths (Median)
Arm A (Induction Then Maintenance With Bevacizumab)4.2
Arm B (Induction Then Maintenance With Pemetrexed5.1
Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)7.5

[back to top]

Overall Survival

"Overall survival is defined as the time from randomization to death or date last known alive.~The primary analysis is among patients who were randomized to the maintenance therapy. Patients who received induction therapy only and did not participate in the randomization part of the study were not included in this analysis." (NCT01107626)
Timeframe: Assessed every 6 weeks during induction therapy and every 3 cycles during maintenance therapy; after discontinuation of study therapy, assessed every 3 months for 2 years and every 6 months for years 3-5

Interventionmonths (Median)
Arm A (Induction Then Maintenance With Bevacizumab)14.4
Arm B (Induction Then Maintenance With Pemetrexed15.9
Arm C (Induction Then Maintenance With Bevacizumab and Pemetrexed)16.4

[back to top]

Median Progression-free Survival Time

Progression-free survival time is defined as the time from first day of treatment to the first date of disease progression or death as a result of any cause. Progression was assessed every 2 cycles of treatment (6 weeks) by CT, CT/PET, or MRI. Progression is defined using RECIST 1.0, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01127763)
Timeframe: up to 1 year

Interventionmonths (Median)
RAD001+Carboplatin3

[back to top]

Toxicity Profile-Hematological

Reported as percentage of patients who experienced grade 3 and higher hematological adverse events (AEs) related to the study drugs. (NCT01127763)
Timeframe: treatment period (up to 1 year) plus 30 days off treatment

,,
Interventionpercentage of patients (Number)
AnemiaThrombocytopeniaLeukopeniaNeutropenia
RAD001+Carboplatin (All Patients)428412
RAD001+Carboplatin (AUC 4)51105
RAD001+Carboplatin (AUC 6 and 5)0711429

[back to top]

Toxicity Profile-Non Hematological

Reported as percentage of patients who experienced grade 3 and higher non-hematological AEs related to the study drugs. (NCT01127763)
Timeframe: treatment period (up to 1 year) plus 30 days off treatment

Interventionpercentage of patients (Number)
NauseaVomitingDehydrationMucositisHypersensitivity
RAD001+Carboplatin (All Patients)44444

[back to top]

Clinical Benefit Rate (Complete Response, Partial Response, and Stable Disease That Lasts More Than 6 Months)

Clinical benefit rate is defined as the number of patients with complete response (CR), partial response (PR), or stable disease (SD) that lasts at least 6 months. Response was assessed every 2 cycles of treatment (6 weeks) by computed tomography (CT), CT/positron emission tomography (PET), or magnetic resonance imaging (MRI). Overall response evaluation is based on Response Evaluation Criteria In Solid Tumors 1.0 (RECIST 1.0). Per RECIST 1.0 for target lesions: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT01127763)
Timeframe: up to 1 year

Interventionpercentage of patients (Number)
RAD001+Carboplatin36

[back to top]

Number of Participants With Dose Limiting Toxicity (DLT)

DLTs were defined as clinically significant adverse events occurring less than or equal to 21 days after commencing study treatment and considered to be possibly or probably related to study treatment by the Investigator. If 1 DLT occurred at any dose level, the cohort was to be expanded to include a maximum of six evaluable subjects. If 2 DLTs occurred at any dose level, the maximum tolerated dose (MTD) was to be either defined as the preceding dose, or an intermediate dose. To evaluate an intermediate dose, an additional dose cohort could be added to more accurately define the MTD. (NCT01133756)
Timeframe: Cycle 1 (21 days)

,,
InterventionParticipants (Number)
Platelet count decreasedThrombocytopenia
Lenvatinib 16 mg (Day 1 to Day 21) + Carboplatin + Gemcitabine10
Lenvatinib 16 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine02
Lenvatinib 8 mg (Day 2 to Day 21) + Carboplatin + Gemcitabine00

[back to top]

Clinical Response

We will summarize clinical response as the proportion of patients with complete response. Complete response will be defined as normalization of CA125. - After 6 cycles of Second Line Adjuvant Chemotherapy. (NCT01144442)
Timeframe: After 6 cycles of Paclitaxel & Carboplatin (Week 21 up to 27)

Interventionparticipants (Number)
HIPC Treatment10

[back to top]

Feasibility of HIPC in Recurrent Disease Setting

We will determine feasibility based on the proportion of patients who complete 6 prescribed cycles of second line chemotherapy after undergoing the HIPC procedure. (NCT01144442)
Timeframe: 6 months

Interventionparticipants (Number)
HIPC Treatment9

[back to top]

Progression-free Survival (PFS)

The length of time during and after the treatment of cancer, that a patient lives with the disease but it does not get worse. (NCT01146795)
Timeframe: Up to 3 years

Interventionmonths (Median)
Carboplatin, Paclitaxel, and Bevacizumab16.8

[back to top]

Response Rate

The percentage of patients whose cancer shrinks or disappears after treatment. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01146795)
Timeframe: Cycle 3, Cycle 6, Cycle 9 and 3 years post-treatment

Interventionpercentage of patients (Number)
Complete responsePartial responseStable disease
Carboplatin, Paclitaxel, and Bevacizumab6.571.022.6

[back to top]

Quality of Life (QOL) Score

The FACT Quality of Life (QOL) Score questionnaire is designed to assess the effects of cancer and its treatment on the quality of life, by measuring aspects of an individual's sense of well-being and ability to carry out various activities. When calculating the total QOL score, the score scale of functional well-being was reversed in order to keep consistent with other three domains. The lower the total score, the better the quality of life. The five-point scale ranges from 0 (not at all) to 4 (very much). Scoring the FACT-G is performed through a simple sum of item scores. Each subscale is scored, and a total score for the FACT-G is obtained by adding each of the subscale scores. With a total possible score greater than 100, additional scoring methods have been used to simplify interpretation. Modifications of scoring include normalizing the total score on a scale of 0-100 through mathematical transformations, as well as the use of a Trial Outcome Index (TOI). (NCT01146795)
Timeframe: Baseline, Cycle 3, Cycle 6, Cycle 9

Interventionscore on a scale (Mean)
Baseline Quality of Life (QOL) ScoreCycle 3 Quality of Life (QOL) ScoreCycle 6 Quality of Life (QOL) ScoreCycle 9 Quality of Life (QOL) Score
Carboplatin, Paclitaxel, and Bevacizumab67.48.96.6

[back to top]

Number of Protocol Defined Adverse Events in Patients Receiving Neoadjuvant Carboplatin, Paclitaxel, and Bevacizumab

"This is to assess the feasibility of delivering multiple cycles of the study treatment without excessive dose modification or cycle delays. The regimen would be considered unfeasible for further study if there were 5 or more of the following events within the first 15 patients, 7 or more of these events within the first 30 patients, or 8 or more of these events within the first 45 patients:~Delay of day 1 of therapy > 3 weeks from the expected day 1 of that cycle~Febrile neutropenia requiring hospitalization~Grade 4 thrombocytopenia~Grade 1-5 gastrointestinal perforation~Grade 3-4 hemorrhagic toxicity~Grade 3-4 arterial thromboembolic complications~Grade 4 hypertension~Grade 4 proteinuria~Fascial dehiscence" (NCT01146795)
Timeframe: Up to 30 days after completion of 9 cycles of treatment and/or early discontinuation (approximately up to 12 months)

Interventionprotocol defined adverse events (Number)
Carboplatin, Paclitaxel, and Bevacizumab7

[back to top]

Median Time to Overall Survival

The time to overall survival is defined as the time to death from any cause. The median was determined via Kaplan Meier methodology. (NCT01151761)
Timeframe: 18 months

Interventionmonths (Median)
SBRT and Chemo8.5

[back to top]

Liver Transplant Rate

The number of patients receiving liver transplant among patients who initially have tumors ≤3 cm (NCT01151761)
Timeframe: 12 months

Interventionparticipants (Number)
SBRT and Chemo0

[back to top]

Freedom From Local Progression at 12 Months

the proportion of patients who experienced a local recurrence at 12 months with death as a competing risk (NCT01151761)
Timeframe: 12 months

Interventionpercentage of patients (Number)
SBRT and Chemo0

[back to top]

Liver Transplant Conversion Rate

The ability to successfully perform liver transplant among patients who initially have tumor >3 cm (NCT01151761)
Timeframe: 12 months

Interventionparticipants (Number)
SBRT and Chemo0

[back to top]

Serum CA 19-9 Levels

Initial level of Cancer antigen 19-9 (NCT01151761)
Timeframe: 12 months

InterventionU/ml (Mean)
SBRT and Chemo3329.1

[back to top]

Progression-free Survival at 12 Months

Progression free survival is defined to be the time to progression of disease or death. (NCT01151761)
Timeframe: 12 months

Interventionparticipants (Number)
SBRT and Chemo0

[back to top]

Pathologic Complete Response Rate

Pathologic complete response will be defined as no residual tumor cells seen on the explanted liver specimen. (NCT01151761)
Timeframe: 12 months

Interventionparticipants (Number)
SBRT and Chemo0

[back to top]

Overall Survival at 12 Months

the estimated probability for the percentage of participants with overall survival at 12 months. (NCT01151761)
Timeframe: 12 months

Interventionprobability (Number)
SBRT and Chemo0

[back to top]

Change in Tumor Size (CTS)

CTS was defined as the log ratio of tumor size at 6 weeks to tumor size at baseline. CTS at 6 weeks=Log (Sum of Target Lesion Measurements at 6 Weeks)-Log (Sum of Target Lesion Measurements at Baseline). (NCT01160744)
Timeframe: Baseline, 6 weeks

Interventionlog ratio (Mean)
Pem + Carb or Cis (Non-Squamous)-0.2
Ram + Pem + Carb or Cis (Non-Squamous)-0.2
Gem + Carb or Cis (Squamous)-0.3
Ram + Gem + Carb or Cis (Squamous)-0.4

[back to top]

Overall Survival (OS)

OS was defined as the time from the date of randomization to the date of death from any cause. If the participant was alive at the end of the follow-up period or was lost to follow-up, OS was censored on the last date the participant was known to be alive. (NCT01160744)
Timeframe: Randomization to the date of death from any cause (up to 31.3 months)

Interventionmonths (Median)
Pem + Carb or Cis (Non-Squamous)10.4
Ram + Pem + Carb or Cis (Non-Squamous)13.9
Gem + Carb or Cis (Squamous)11.3
Ram + Gem + Carb or Cis (Squamous)10.4

[back to top]

Percentage of Participants With Best Overall Response of Complete Response (CR) or Partial Response (PR) [Objective Response Rate (ORR)]

Best overall response of CR or PR was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR was defined as ≥30% decrease in SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR/total number of participants)*100. (NCT01160744)
Timeframe: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)

Interventionpercentage of participants (Number)
Pem + Carb or Cis (Non-Squamous)38.0
Ram + Pem + Carb or Cis (Non-Squamous)49.3
Gem + Carb or Cis (Squamous)24.6
Ram + Gem + Carb or Cis (Squamous)46.5

[back to top]

Percentage of Participants With CR, PR, or Stable Disease (SD) [Disease Control Rate (DCR)]

DCR: percentage of participants with CR, PR, or SD using RECIST v 1.1 criteria. CR: disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker levels of non-target lesions. PR: ≥30% decrease in SOD of target lesions taking as reference baseline sum diameter. PD: ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference smallest sum of longest diameters recorded since treatment started and an absolute increase in sum diameter ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. SD: neither sufficient shrinkage to qualify for PR nor increase to qualify for PD. Participants who had no post baseline tumor assessments were considered non-responders and included in the denominator when calculating response rate. Percentage of participants=(number of participants with CR+PR+SD/total number of participants)*100. (NCT01160744)
Timeframe: Day 1, Cycle 1 (3-week cycles) and every 6 weeks thereafter to PD (up to 24 months)

Interventionpercentage of participants (Number)
Pem + Carb or Cis (Non-Squamous)70.4
Ram + Pem + Carb or Cis (Non-Squamous)85.5
Gem + Carb or Cis (Squamous)66.7
Ram + Gem + Carb or Cis (Squamous)73.2

[back to top]

Progression-Free Survival (PFS)

PFS was the time from randomization to the first objective progression as defined by Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v 1.1) or death from any cause, whichever occurred first. Progressive disease (PD) was defined as ≥20% increase in sum of diameter (SOD) of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 millimeters (mm); appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants alive and without disease progression were censored at the time of the last objective tumor assessment. Participants who did not progress and were lost to follow-up were censored at their last radiographic assessment. If no baseline or post baseline radiologic assessments were available, participants were censored at date of randomization. (NCT01160744)
Timeframe: Randomization to PD or death (up to 24 months)

Interventionmonths (Median)
Pem + Carb or Cis (Non-Squamous)5.6
Ram + Pem + Carb or Cis (Non-Squamous)7.2
Gem + Carb or Cis (Squamous)5.4
Ram + Gem + Carb or Cis (Squamous)5.6

[back to top]

Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Who Died

Data presented are the number of participants with at least 1 treatment-emergent adverse event (TEAE) and treatment-emergent serious adverse event (SAE), as well as, the number of participants who died during the study. TEAEs were defined as serious and other non-serious AEs that occurred or worsened after study treatment (regardless of causality). A summary of SAEs and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. (NCT01160744)
Timeframe: Day 1, Cycle 1 (3-week cycles) Up to 3 Years

,,,
InterventionParticipants (Count of Participants)
Treatment-Emergent SAETreatment-Emergent Adverse EventDeaths
Gem + Carb or Cis (Squamous)296355
Pem + Carb or Cis (Non-Squamous)386851
Ram + Gem + Carb or Cis (Squamous)397156
Ram + Pem + Carb or Cis (Non-Squamous)446755

[back to top]

Duration of Response (DOR)

DOR was measured from the time criteria were met for the first objectively recorded CR or PR until the first date criteria for PD were met or death. Response was defined using RECIST v 1.1 criteria. CR was defined as the disappearance of all lesions, pathological lymph node reduction in short axis to <10 mm, and normalization of tumor marker level of non-target lesions. PR was defined as ≥30% decrease SOD of target lesions taking as reference the baseline sum diameter. PD was defined as ≥20% increase in SOD of target lesions and short axes of target lymph nodes, taking as reference the smallest sum of the longest diameters recorded since treatment started and an absolute increase in sum diameter of ≥5 mm; appearance of ≥1 new lesions and/or unequivocal progression of existing non-target lesions. Participants who did not relapse were censored at the day of their last objective tumor assessment. (NCT01160744)
Timeframe: Time of first response (CR or PR) until PD or death (up to 24 months)

Interventionmonths (Median)
Pem + Carb or Cis (Non-Squamous)4.5
Ram + Pem + Carb or Cis (Non-Squamous)5.5
Gem + Carb or Cis (Squamous)4.3
Ram + Gem + Carb or Cis (Squamous)4.3

[back to top]

Maximally Tolerated Dose of Bendamustine Hydrochloride That Can be Combined With Rituximab, Carboplatin, and Etoposide Chemotherapy in Patients With Relapsed or Refractory Lymphoid Malignancies

Defined as dose at which approximately =< 25% of patients experience a DLT. Following completed observation of final patient, two-parameter logistic model fit to data, generating dose-response curve based on observed toxicity rate at dose levels visited. Based on this fitted model, MTD is estimated to be dose that is associated with toxicity rate of 25%. If estimate of slope parameter for fitted curve is not positive and finite, geometric mean of dose level used for last cohort and dose level that would have been assigned to next cohort is taken as MTD. (NCT01165112)
Timeframe: Up to 5 weeks after the last course

Interventionmg/m2 x 2 (Number)
Treatment (Chemotherapy and Monoclonal Antibody Therapy)120

[back to top]

Safety and Toxicity of This Regimen

Count of participants experiencing a dose limiting toxicity. The National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 will be used to classify and grade toxicities. (NCT01165112)
Timeframe: Up to 5 weeks after the last course

InterventionParticipants (Count of Participants)
Treatment (Chemotherapy and Monoclonal Antibody Therapy)0

[back to top]

Preliminary Assessment of the Efficacy of This Regimen

Response will be defined by standard NCI criteria (Cheson et al) for lymphoid malignancies. (NCT01165112)
Timeframe: Up to 5 weeks after the last course

InterventionParticipants (Count of Participants)
Treatment (Chemotherapy and Monoclonal Antibody Therapy)33

[back to top]

Ability to Proceed to Peripheral Blood Stem Cell (PBSC) Collection Following Treatment (Impact of This Regimen on Stem Cell Reserve)

(NCT01165112)
Timeframe: Up to 5 weeks after the last course

InterventionParticipants (Count of Participants)
Treatment (Chemotherapy and Monoclonal Antibody Therapy)30

[back to top]

Trough Observed Serum Concentration (Cmin) of Ipilimumab

Cmin was recorded directly from experimental observations. Actual times were used for the analyses. Cmin measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 (Day 8), and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure. (NCT01165216)
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

,
Interventionug/mL (Mean)
Day 22Day 43 (n=3, 5)Day 64 (n=3, 3)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin11.0610.9813.90
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin26.6526.6826.40

[back to top] [back to top]

Number of Participants With Best Overall Response (BOR) of Partial Response (PR) or Stable Disease

Tumor response was determined for all participants with measurable lesions by radiologic responses as defined by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The BOR was the best response recorded from start of treatment until disease progression/recurrence. RECIST for target lesions: PR=at least a 30% decrease in the sum of the longest dimension (LD) of target lesions, taking as reference the baseline sum LD; stable disease=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started. At minimum, tumor measurements were to be obtained at screening, every 6 weeks (±1 week) during the induction phase and every 12 weeks (±1 week) during the maintenance phase. (NCT01165216)
Timeframe: Day 1 of Cycle 3, Day 1 of Cycle 5, and Day 22 of Cycle 6

,
InterventionParticipants (Number)
PRStable disease
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin33
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin34

[back to top]

Time of Maximum Observed Serum Concentration (Tmax)

Tmax was recorded directly from experimental observations. Actual times were used for the analyses. Tmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure. (NCT01165216)
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

InterventionHours (Median)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin2.75
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin3.98

[back to top]

Serum Half-life (T-HALF) of Ipilimumab

T-HALF was calculated as the ratio of ln(2) to elimination rate constant (K), where K was estimated as negative slope obtained by regression of the terminal log-linear portion of the serum concentration vs time profile following the ipilimumab dose on Day 1 of Cycle 3. Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods, using a validated PK analysis program. Actual times were used for the analyses. T-HALF measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure. (NCT01165216)
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

InterventionDays (Mean)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin13.3
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin11.3

[back to top]

Number of Participants Experiencing a Dose-limiting Toxicity (DLT)

A DLT was defined as study drug-related adverse event occurring during the first 2 cycles after ipilimumab administration in the induction phase and was any of the following: Grade 4 absolute neutrophil count (ANC) decreased (<500 cells/ mm^3) for 7 or more consecutive days; febrile Neutropenia (body temperature ≥38.5° C with ANC <1000 /mm^3) lasting >3 days; Grade 4 platelet count decreased (<25,000 cells/mm^3) or Grade 3 platelet count decreased requiring a platelet transfusion; Grade 3 or greater nausea, vomiting, diarrhea, despite the use of adequate/maximal medical intervention; Grade 3 or greater aspartate transaminase/alanine transaminase level and rash that has not resolved to Grade 2 or lower within 2 weeks after onset; or any Grade 3 or greater nonhematologic toxicity (except Grade 3 fatigue, Grade 3 asthenia, Grade 3 transient arthralgia/myalgia, or Grade 3 transient abnormal electrolyte levels). (NCT01165216)
Timeframe: Day 1 of Cycles 1 and 2 From Day 1 of Cycle 3 to Day 21 of Cycle 4

InterventionParticipants (Number)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin2
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin1

[back to top]

Maximum Serum Concentration (Cmax) of Ipilimumab

Cmax was recorded directly from experimental observations. Actual times were used for the analyses. Cmax measurements were performed during the 3rd cycle; at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent, or study closure. (NCT01165216)
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

Interventionug/mL (Geometric Mean)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin72.8
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin201

[back to top]

Area Under the Concentration Curve From Time 0 to Day 21 (in 1 Interval Dosing) (AUC[0-21d]) for Ipilimumab

The AUC(0-21d) was calculated using a mixture of log- and linear-trapezoidal summations. Using no weighting factor, the terminal log-liner phase of the concentration-time curve was determined by least-square linear regression of at least 3 data points. Individual patient pharmacokinetic (PK) parameter values were derived by noncompartmental methods using a validated PK analysis program. Actual times were used for the analyses. AUC(0-21d) measurements were performed during the 3rd cycle, at predose and at 1.5, 4 , 24 (Day 2), 48 (Day 3), 168 hrs (Day 8),and 336 (Day 15) hours postdose; during the 4th and subsequent cycle, predose ipilimumab; and off-treatment until progression of disease, toxicities requiring discontinuation, withdrawal of consent; or study closure. (NCT01165216)
Timeframe: During Cycle 3: predose and 1.5, 4, 24, 48, 168, and 336 hours postdose ipilimumab

Interventionug*h/mL (Geometric Mean)
Dose Level 1: Ipilimumab, 3 mg/kg + Paclitaxel + Carboplatin12632
Dose Level 2: Ipilimumab, 10 mg/kg + Paclitaxel + Carboplatin36489

[back to top]

Time to Disease Progression

Progression = at least a 20% increase in the sum of the longest diameter of the target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions, appearance of one or more new lesions, unequivocal progression of existing non-target lesions. (NCT01167192)
Timeframe: Up to 5 years from registration

Interventionmonths (Median)
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation6.5

[back to top]

Medical Toxicities as Measured by Number of Grade 3 or Higher Adverse Events

(NCT01167192)
Timeframe: 30 days post surgery (approximately 16-20 weeks after start of registration)

Interventionadverse event (Number)
AnemiaLeukocytosisCardiac arrestPulseless electrical activitySinus bradycardiaFeverWound infectionRadiation recall reaction (dermatologic)Alanine aminotransferase increasedCreatinine increasedLymphocyte count decreasedNeutrophil count decreasedPlatelet count decreasedWeight gainHyponatremiaBack painCerebrovascular accidentAcute kidney injuryCellulitisHypertension
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation11111111114111111111

[back to top]

Response Rate as Measured by Number of Participants Who Achieved Complete Response (CR) or Partial Response (PR)

"Complete response (CR) = disappearance of all target lesions, disappearance of all non-target lesions and normalization of tumor marker level.~Partial response (PR) = at least a 30% decrease in the sum of the longest diameter (LD) of the target lesions taking as reference the baseline sum LD" (NCT01167192)
Timeframe: Prior to surgery (approximately 12-16 weeks from registration)

InterventionParticipants (Count of Participants)
Pathologic complete responsePartial response
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation33

[back to top]

Number of Participants With Surgical Complications

(NCT01167192)
Timeframe: 30 days post surgery (approximately 16-20 weeks from registration)

Interventionparticipant (Number)
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation1

[back to top]

Overall Survival Rate

(NCT01167192)
Timeframe: Median follow-up was 59.9 months

Interventionpercentage of participants (Number)
Neoadjuvant Cisplatin or Carboplatin AUC 6 & Radiation75

[back to top]

Median Duration of First Quartile Survival

First Quartile Overall Survival (NCT01167712)
Timeframe: The timeframe is from enrollment onto the study up to 3 years after enrollment

Interventionmonths (Median)
Arm I (Adjuvant Chemotherapy Suboptimally Debulked)23.2
Arm II (Neoadjuvant Chemotherapy)24

[back to top]

Quality of Life Score as Measured by Functional Assessment of Cancer Therapy-Ovary-Total Outcome Index (Fact-O TOI)

Mean quality of life score after 6 cycles of study treatment estimated from a mixed model. The FACT-O-TOI is composed of three subscales: Physical Well Being (PWB) (7 Items), Functional Well Being (FWB) (7 items), and Ovarian Cancer Subscale (OCS) (12 items). Each item in the FACT-O TOI are scored using a 5-point scale (0=not at all; 1=a little bit; 2=somewhat; 3=quite a bit; 4=very much). A subscale score is computed as long as more than 50% of subscale items have been answered. A Total score of the FACT-O TOI is the summation of the three subscale scores; if more than 80% of the FACT-O TOI items provide valid responses and all three subscales have valid scores. A score of the FACT-O TOI is ranged 0-104 with a larger score indicating a more preferred state of health-related quality of life (HRQOL) (NCT01167712)
Timeframe: 18 weeks after enrolling on the study, which is the time it takes to complete 6 cycles of treatment plus 3 weeks

InterventionUnits on a Scale (Mean)
Arm I (Adjuvant Chemotherapy Suboptimally Debulked)70.9
Arm II (Neoadjuvant Chemotherapy)68.2

[back to top]

Progression-Free Survival

First progression or death for weekly paclitaxel treatment relative to standard 3 week paclitaxel. Progression is defined using response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01167712)
Timeframe: The timeframe is from enrollment onto the study up to 3 years following enrollment.

Interventionmonths (Median)
Arm I (Adjuvant Chemotherapy Suboptimally Debulked)14.7
Arm II (Neoadjuvant Chemotherapy)14.0

[back to top]

Maximum Tolerated Dose (MTD) of Panobinostat + ICE

Maximum Tolerated Dose (MTD) of Panobinostat + ICE (NCT01169636)
Timeframe: From first dose of panobinostat (or chemotherapy, in the arm of ICE alone) until 30 days after last dose, up to 6 years

Interventionmg (Number)
Phase I: Panobinostat + ICE (Maximal Tolerated Dose (MTD)30

[back to top]

Percentage of Participants With Failure Free Survival (FFS)

FFS duration was calculated from date of study entry to date of progression or death or change of therapy, whichever came first. (NCT01169636)
Timeframe: 16 months

Interventionpercentage of participants (Number)
Phase I: Panobinostat + ICE (Maximal Tolerated Dose (MTD)61
Phase II: Standard of Care (ICE)82
Phase II Panobinostat + ICE75

[back to top]

Number of Participants With Complete Remission (CR)

Will be assessed by Kaplan-Meier methods. (NCT01169636)
Timeframe: Assessed after 3 cycles of ICE (2 months)

,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable DiseaseProgressive Disease
Phase I: Panobinostat + ICE (Maximal Tolerated Dose (MTD)21422
Phase II Panobinostat + ICE9020
Phase II: Standard of Care (ICE)8121

[back to top]

Optimal Interval Between the End of Axitinib Therapy and Initiation of Chemotherapy

Optimal interval between the end of axitinib therapy and initiation of chemotherapy, as determined using FLT PET as a Radiological Biomarker information of Resumption of DNA Synthesis Following Axitinib Therapy. (NCT01174238)
Timeframe: Days 1, 14, 17, and 20 of cycle 1

Interventiondays (Number)
Axitinib + Carboplatin/Paclitaxel With FLT-PET Scans7

[back to top]

Overall Survival (OS)

Overall survival is the duration from first dose of study medication to death. For participants who are alive, overall survival is censored at the last contact. (NCT01174238)
Timeframe: Baseline until death or up to 24 months

Interventionmonths (Median)
Axitinib+Carboplatin/Paclitaxel, Including FLT-PET Patients14.0

[back to top]

Objective Response Rate (ORR)

ORR is defined as the percentage of patients with tumor size reduction, i.e. the sum of partial responses plus complete responses. Radiographic response was evaluated using RECIST criteria during every 21-day cycle of treatment. (NCT01174238)
Timeframe: Monthly during study treatment, up to 12 months

Interventionpercentage of patients (Number)
Axitinib + Carboplatin/Paclitaxel22

[back to top]

Increase From Nadir in the Sum of Maximum (18)F-FLT Uptake Values After Treatment Holiday

(18)F-FLT uptake values following a 7-day treatment holiday compared to the lower of Baseline or Day 14 value. (NCT01174238)
Timeframe: Baseline, Day 14, Day 20

Interventionparticipants (Number)
Axitinib + Carboplatin/Paclitaxel With FLT-PET Scans4

[back to top]

Time to Progression (TTP)

(NCT01174238)
Timeframe: within 7 days of odd cycles after cycle 1 for the duration of treatment, up to 12 cycles

Interventionmonths (Median)
Axitinib+Carboplatin/Paclitaxel, Including FLT-PET Patients8.7

[back to top]

The Number of Participants With Adverse Events

To determine the safety and tolerability of Vandetanib when given in combination with chemotherapy and radiation therapy as evaluated by serial blood tests, electrocardiograms, and physical assessments during therapy and for four weeks following surgery (NCT01183559)
Timeframe: Within 4 weeks of initiation of chemo/radiation therapy

InterventionParticipants (Count of Participants)
Vandetanib2

[back to top]

Maximum Tolerated Dose of Vandetanib

To determine the maximum tolerated dose (MTD) of Vandetanib given concurrently with chemotherapy and radiation therapy followed by surgery (esophagectomy)evaluated by the frequency, severity and duration of adverse events that occur during treatment and for four weeks following surgery as measured by serial blood tests, electrocardiograms and physical assessments (NCT01183559)
Timeframe: Within 4 weeks of initiation of chemo/radiation therapy

Interventionmilligrams (Number)
Vandetanib100

[back to top]

Maximum Tolerated Dose (MTD)

The maximum tolerated dose of Pralatrexate in combination with Carboplatin in this patient population. The unit is given in milligrams per square meter of body surface area. MTD was determined using a standard 3 + 3 dose escalation cohort, where 3 participants were enrolled on the starting dose of 30 mg/m2 and if no dose limiting toxicities (DLT) were experienced after a full cycle, 3 additional participants were enrolled at the next highest dose level. Each increase in dose level escalated the dose of Pralatrexate by 15 mg/m2. If during any dose level, 1 patient out of 3 develops a DLT, then 3 additional patients will be added to that dose level. If 2 out of the 3 patients placed on any dose level experience a DLT, the preceding dose is considered MTD. If 1/6 has a DLT, the next higher dose level will commence accrual (unless at level +5 and then accrual to the Phase I portion will stop). If ≥ 2 of 6 patients have a DLT, then the preceding dose will be considered MTD. (NCT01188876)
Timeframe: 1 year

Interventionmg/m^2 (Number)
Carboplatin/Pralatrexate105

[back to top]

Maximum Concentration of Drug in Plasma (Cmax)

The maximum concentration of Pralatrexate at day 1 and 15 among phase 1 participants dosed at 105 milligrams per square meter of body surface area (mg/m2). The concentration is given in micrograms per milliliter. (NCT01188876)
Timeframe: Day 1 and Day 15

Interventionug/ml (Mean)
Day 1Day 15
Carboplatin/Pralatrexate23.8717.61

[back to top]

Area Under the Plasma Drug Concentration-Time Curve (AUC)

Area under the plasma drug concentration-time curve (AUC) for phase 1 participants that were dosed at 105 mg/m2. AUC represents the actual body exposure to drug after administration of a dose of the drug and is expressed in micrograms * hour per milliliter (ug*h/mL). (NCT01188876)
Timeframe: Day 1 and Day 15

Interventionug*h/mL (Mean)
Day 1Day 15
Carboplatin/Pralatrexate9.898.01

[back to top]

Progression Free Survival

The number of participants alive and without disease progression at the given time-points. Time is measured from the start of treatment. Progression is defined as having at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT01188876)
Timeframe: 3 months, 6 months

InterventionParticipants (Count of Participants)
3 Months6 Months
Carboplatin/Pralatrexate4440

[back to top] [back to top]

Overall Survival

The number of participants still alive at the given time points. The duration of time is measured from the start of treatment until death due to any cause, participants are censored at the date of the last evaluation. The number participants surviving at 6, 12, 18, and 24 months is shown. (NCT01188876)
Timeframe: 6, 12, 18, and 24 months

InterventionParticipants (Count of Participants)
6 Months12 Months18 Months24 Months
Carboplatin/Pralatrexate49494633

[back to top]

Disease-free Survival (DFS)

A disease event is defined as local/regional persistence or recurrence of the cancer under study, distant metastases, a new second primary cancer, or death due to any cause. Participants undergoing surgery who had an R2 resection and participants not undergoing surgery who had a positive endoscopic biopsy or no biopsy at all were considered to have local persistence of disease. Disease-free survival time is defined as time from randomization to the date of first disease event or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis was to occur after 162 events were reported. (NCT01196390)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 8.0 years.

Interventionmonths (Median)
Chemoradiation and Trastuzumab (Arm 1)19.6
Chemoradiation (Arm 2)14.2

[back to top]

Number of Participants With Any Cardiac Adverse Events Regardless of Attribution

Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event (AE) severity from 1=mild to 5=death. Logistic regression was used to evaluate treatment arm, clinical tumor stage (T stage), Zubrod Performance Status, gender, presence of adenopathy, and age as possible predictors of cardiac adverse events. Results of the final model are reported in the statistical analysis section. Summary adverse event data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. (NCT01196390)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

InterventionParticipants (Count of Participants)
Chemoradiation and Trastuzumab (Arm 1)30
Chemoradiation (Arm 2)24

[back to top]

Overall Survival

Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Rates are estimated by the Kaplan-Meier method. Analysis occurred after 109 deaths were reported. (NCT01196390)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

Interventionmonths (Median)
Chemoradiation and Trastuzumab38.5
Chemoradiation38.9

[back to top]

Percentage of Participants With Pathologic Complete Response at Surgery

Pathologic Complete Response (pCR) is evaluated after surgery and is based on the pathology review of the submitted surgical specimen. Pathologic Complete Response occurs if the pathologist determines that the resected esophageal specimen, accompanying lymph nodes, and surgical margins are all free of tumor. (NCT01196390)
Timeframe: At the time of surgery, 5-8 weeks after completion of radiation therapy.

Interventionpercentage of participants (Number)
Chemoradiation and Trastuzumab27
Chemoradiation29

[back to top]

Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment

The ECS is a 17-item self-report instrument designed to measure multidimensional quality of life in patients with esophagus cancer with a total score ranging from 0-68. It is to be administered with the Functional Assessment of Cancer Therapy - General (FACT-G). A higher score indicates better QOL. Improvement is defined as an increase from the baseline score of at least 5 points. (NCT01196390)
Timeframe: Baseline, 6-8 weeks after end of radiation therapy (approximately 11.5-13.5 weeks from treatment start), 1 and 2 years from treatment start

,
Interventionpercentage of participants (Number)
6-8 weeks from end of treatment1 year from start of treatment2 years from start of treatment
Chemoradiation384227
Chemoradiation and Trastuzumab463941

[back to top]

Frequency of Highest Grade Adverse Event Per Participant

Common Terminology Criteria for Adverse Events (version 4.0 before 4-1-2018; then version 5.0) grades adverse event severity from 1=mild to 5=death. Summary data provided is in this outcome measure; see Adverse Events Module for specific adverse event data. (NCT01196390)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 8 years.

InterventionParticipants (Count of Participants)
All Adverse Events72423036All Adverse Events72423037Reported as Definitely, Probably, or Possibly Related to Protocol Treatment72423036Reported as Definitely, Probably, or Possibly Related to Protocol Treatment72423037
Grade 1Grade 2Grade 3Grade 4Grade 5
Chemoradiation and Trastuzumab0
Chemoradiation0
Chemoradiation and Trastuzumab14
Chemoradiation12
Chemoradiation and Trastuzumab49
Chemoradiation56
Chemoradiation and Trastuzumab27
Chemoradiation25
Chemoradiation and Trastuzumab5
Chemoradiation3
Chemoradiation and Trastuzumab2
Chemoradiation20
Chemoradiation and Trastuzumab41
Chemoradiation52
Chemoradiation and Trastuzumab20
Chemoradiation21

[back to top]

Frequency and Severity of Toxicity

Grade 3 or higher adverse events were graded by CTC AE v4 (NCT01196429)
Timeframe: Each cycle while on treatment

,
Interventionparticipants (Number)
Neutrophil count decreasedWhite blood cell decreasedAnemiaPlatelet count decreasedHypertensionhypertriglyceridemiaMucositis oralFebrile neutropeniaDiarrheaHypokalemiaHyperglycemiaAbdominal painLymphocyte count decreasedNauseaUrinary tract infectionGGT increasedEdema limbsFatigueFeverNon-cardiac chest painCholesterol highWeight gainHypoalbuminemiaHyponatremiaHypophosphatemiaPeripheral Sensory neuropathyCoughDyspneaPharyngeal mucositisRash maculo-papularColonic perforationConstipationIleusOral painSmall intestinal obstructionVomitingPainCholecystitisHepatobiliary disorders-otherAppendicitis perforatedKidney infectionLung infectionPeripherl nerve infectionPharyngitisSkin infectionInfections and infestations -otherAlanine aminotransferase increasedAspartate aminotransferase increasedCreatiine increasedAnorexiaDehydrationHypermagnesemiaBack PainBone PainFlank painPain in ExtremityDizzinessParesthesiaVasovagal reactionAnxietyDysparenuiaPneumonitisSore throatHypotensionLymphocele
Japan4232131010755242122030110201022002110000000110001001111010000100001000
US/Korea36279104654634321302112021200220101111111001110110000101111011110111

[back to top]

Proportion of Patients Who Are Alive and Progression-free for at Least 12 Months After Study Entry in Patients With Newly Diagnosed Stage III or IV Clear Cell Ovarian Cancer in the Following Populations: Patients in the U.S./Worldwide and Japan

Progression of target lesions (TL) was a >=20% increase in the sum of the diameters of TL, taking as reference the smallest sum on study (including the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must demonstrate an absolute increase >=5 mm. Progression of non-target lesions (NTL) as defined as appearance of >=1 new lesions or unequivocal progression of existing NTL. Unequivocal progression should not normally trump target lesion status; it must be representative of overall disease status change, not a single lesion increase. Clear progression of only NTL is exceptional, but the opinion of the treating physician should prevail in such circumstances, and the progression status should be later confirmed by a review panel (or Principal Investigator). Progression of TL, unequivocal progression of NTL, or new lesions constitutes progression. This description is abbreviated; see the RECIST 1.1 manuscript for further details. (NCT01196429)
Timeframe: Tumor scans were done every other cycle for the first 6 months; then every 3 months x2; then every 6 months thereafter; and at any other time if clinically indicated or signs suggestive of progressive disease or rising levels; for up to 5 years.

Interventionpercentage of participants (Number)
US/Korea43
Japan53

[back to top]

Progression-free Survival

Progression-free survival (PFS) was defined as the period from study entry until disease progression, death, or the last date of contact. Progression was based on RECIST 1.1 (NCT01196429)
Timeframe: Tumor scans were done every other cycle for the first 6 months; then every 3 months x 2; then every 6 mths thereafter; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising tumor mark

Interventionmonths (Median)
US/Korea11.0
Japan12.1

[back to top]

Overall Survival

Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. (NCT01196429)
Timeframe: Every cycle during treatment, then every 3 months for the first 2 years, then every six months for the next three years and then annually for the next 5 years.

Interventionmonths (Median)
US/Korea22.6
Japan25.6

[back to top]

Objective Tumor Response

Complete and Partial Tumor Response by RECIST 1.1. RECIST1.1 is a multi-page paper, and response is defined in the protocol across multiple pages, so it is not practical to define response here. (NCT01196429)
Timeframe: Every other cycle for first 6 months; then every 3 months for two years; then every six months for the next three years; and at any other time if clinically indicated based on symptoms or physical signs suggestive of progressive disease or rising serum tu

Interventionpercentage of participants (Number)
US/Korea54
Japan71

[back to top]

Best Overall Response and Objective Response Rate Following Administration of CS-7017 in Combination With Carboplatin/Paclitaxel in Chemotherapy-naïve Subjects With Metastatic or Unresectable Locally Advanced Non-small Cell Lung Cancer (NSCLC)

The best overall response is the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses from the start of treatment until the participant withdraws from the study. Participants who did not have a tumor assessment, the best overall response is Not Evaluable (NE). The response rate was defined as the proportion of participants with a best overall response of CR or PR, ie, [confirmed and unconfirmed, (CR + PR) / number of participants]. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, CR was defined as the disappearance of all target lesions, PR was defined as ≥30% decrease in the sum of diameters of target lesions, PD was defined as ≥20 increase in the smallest sum of diameters, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT01199055)
Timeframe: Baseline up to Week 18 postdose

,,,,
InterventionParticipants (Count of Participants)
Complete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)Not evaluable (NE)MissingResponse rate (CR + PR)
CS-7017 0.25 mg BID; Initial Portion0012000
CS-7017 0.50 mg BID; Additional Portion0422004
CS-7017 0.50 mg BID; Initial Portion0201002
CS71017 0.5 mg BID; Initial and Additional Portion0623006
Overall0635006

[back to top]

Pharmacokinetic Parameter Area Under the Concentration Versus Time Curve of Geometric Means of Serum Free Form of CS-7017 (R-150033) After Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

The area under the concentration versus time curve during dosing interval (AUCtau) and up to the last quantifiable time (AUClast) of geometric means of CS-7017 are reported at selected cycles (C) and days (D). (NCT01199055)
Timeframe: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose

,,
Interventionng*h/mL (Mean)
Cycle 1, Week 1: AUCtauCycle 1, Week 1: AUClastCycle 2, Week 4: AUCtauCycle 2, Week 4: AUClast
CS-7017 0.25 mg BID; Initial Portion70.6649.57132.4795.94
CS-7017 0.50 mg BID; Additional Portion203.9981.54400.89268.00
CS-7017 0.50 mg BID; Initial Portion209.3387.23345.56240.61

[back to top]

Pharmacokinetic Parameter Observed Serum Concentration (Cmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

The maximum serum concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D). (NCT01199055)
Timeframe: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose

,,
Interventionng/mL (Mean)
Cycle 1, Week 1: CmaxCycle 2, Week 4: Cmax,ss
CS-7017 0.25 mg BID; Initial Portion8.9013.63
CS-7017 0.50 mg BID; Additional Portion14.5439.58
CS-7017 0.50 mg BID; Initial Portion15.9833.83

[back to top]

Pharmacokinetic Parameter Time of Maximum Plasma Concentration (Tmax) of Geometric Means of Serum Free Form of CS-7017 (R-150033) Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

The time of maximum plasma concentration (including at steady state (ss) of CS-7017 are reported at selected cycles (C) and days (D). (NCT01199055)
Timeframe: Initial C1D1, C2D22 and additional C1D3, C2D22 predose, 0.5, 1, 2, 3, 4, 6 and 10h; initial and additional D8 predose; additional D1 predose and 3h; initial and additional D15 predose and 1-3h; C3D43 and C4D64 any time, except additional C3D43 predose

,,
Interventionh (Median)
Cycle 1, Week 1: TmaxCycle 2, Week 4: Tmax,ss
CS-7017 0.25 mg BID; Initial Portion3.903.17
CS-7017 0.50 mg BID; Additional Portion5.953.88
CS-7017 0.50 mg BID; Initial Portion3.003.98

[back to top]

Treatment-Emergent Adverse Events Occurring in Participants in Any Treatment Group During Cycle 1 Following Administration of CS-7017 and Carboplatin/Paclitaxel in Participants With Stage IIIb/IV Non-small Cell Lung Cancer

Treatment-emergent adverse events (TEAEs) are defined as those adverse events that occur, having been absent before the study, or worsen in severity after the initiation of study drug. (NCT01199055)
Timeframe: Baseline to end of Cycle 1, with each treatment cycle being 3 weeks

,,
InterventionParticipants (Count of Participants)
At least one TEAEBlood and lymphatic system disordersNeutropeniaAnaemiaMetabolism and Nutrition DisordersDecreased appetiteNervous System DisordersNeuropathy peripheralRespiratory, Thoracic and Mediastinal DisordersPleural effusionGastrointestinal DisordersNauseaSkin and Subcutaneous Tissue DisordersAlopeciaPruritusMusculoskeletal and Connective Tissue DisordersMyalgiaAthralgiaGeneral Disorders & Administration Site ConditionsFatigueInvestigationsWeight increased
CS-7017 0.25 mg BID; Initial Portion3330001010222203213300
CS-7017 0.50 mg BID; Additional Portion9875664444618817605187
CS-7017 0.50 mg BID; Initial Portion4220211100112122021022

[back to top] [back to top]

Number of Participants With Response

Tumor response by Response Evaluation Criteria in Solid Tumors for participants with measurable disease defined by presence of at least 1 measurable lesion at baseline: Complete Response (CR): disappearance all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial Response (PR): >30% decrease in sum of LD of target lesions (LD) of target lesions taking as reference baseline sum LD determined by two consecutive observations not less than four weeks apart. Progression (PD): >20% increase in sum of LD of target lesions references smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking references smallest sum LD since treatment started. Measurable: lesions accurately measured in at least 1 dimension (longest diameter to be recorded) as 20 mm with conventional techniques or as 10 mm with spiral CT s (NCT01200342)
Timeframe: Following two 3-week cycles

InterventionParticipants (Number)
Complete Response (CR)Partial Response (PR)Progressive Disease (PD)Stable Disease (SD)
Genasense + Paclitaxel + Carboplatin0016

[back to top]

Overall Response Rate (Percentage Subjects With Confirmed Complete or Partial Response)

Tumor response by Response Evaluation Criteria in Solid Tumors for participants with measurable disease defined by presence of at least 1 measurable lesion at baseline: Complete Response (CR): disappearance all target lesions determined by 2 consecutive observations not less than 4 weeks apart. Partial Response (PR): >30% decrease in sum of LD of target lesions (LD) of target lesions taking as reference baseline sum LD determined by two consecutive observations not less than four weeks apart. Progression (PD): >20% increase in sum of LD of target lesions references smallest sum LD recorded since treatment started or appearance of one or more new lesions. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking references smallest sum LD since treatment started. Measurable: lesions accurately measured in at least 1 dimension (longest diameter to be recorded) as 20 mm with conventional techniques or as 10 mm with spiral CT s (NCT01200342)
Timeframe: Following two 3-week cycles

InterventionPercentage of Participants (Number)
Genasense + Paclitaxel + Carboplatin0

[back to top]

Progression-free Survival (PFS)

Progression free survival (PFS) was calculated in days from the date of registration until the earliest date of documented disease progression or death. The median PFS time with 95% confidence interval (CI) was estimated using Kaplan Meier method. The progression-free survival was assessed utilizing computer tomography (CT)/ magnetic resonance imaging (MRI)/bone scans and X-ray and Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. (NCT01201265)
Timeframe: From the date of registration until the disease progression or death (up to 1541 days).

Interventiondays (Median)
All Participants255

[back to top]

Change From Baseline to Cycle 6 in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-30)

The EORTC QLQ-C30 (version 3.0) questionnaire incorporates 9 multi scale items: 5 functional scales (physical, role, cognitive, emotional and social); 3 symptom scales (fatigue, pain and nausea & vomiting); and a global health and quality-of-life scale. It contains 30 questions. The score for each item and the overall score ranges from 0 to 100. A high overall scale and subscale scores represent improved health status. However, in case of symptoms, higher scores suggest increased perception of these symptoms. (NCT01201265)
Timeframe: Baseline, cycle 6

Interventionunits on a scale (Mean)
Baseline; physical (n=40)Change at Cycle 6; physical (n=28)Baseline; role (n=40)Change at Cycle 6; role (n=28)Baseline; cognitive (n=40)Change at Cycle 6; cognitive (n=28)Baseline; emotional (n=40)Change at Cycle 6; emotional (n=28)Baseline; social (n=40)Change at Cycle 6; social (n=28)Baseline; fatigue (n=40)Change at Cycle 6; fatigue (n=28)Baseline; pain (n=40)Change at Cycle 6; pain (n=28)Baseline; nausea and vomiting (n=40)Change at Cycle 6; nausea and vomiting (n=28)Baseline; global health & QOL (n=40)Change at Cycle 6; global health & QOL (n=28)
All Participants69.33-8.8271.26-5.3674.58-4.1761.87-15.7865.42-8.3342.218.3534.5813.0916.672.3858.55-3.86

[back to top]

Percentage of Participants Achieving a Clinical Benefit Response (CBR)

Clinical benefit response was defined as a complete response (CR), partial response (PR) or stable disease (SD). CBR was assessed using Recist v.1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT01201265)
Timeframe: From the date of registration until the disease progression or death (up to 1541 days)

Interventionpercentage of participants (Number)
All Participants92.5

[back to top]

Change From Baseline in Systolic Blood Pressure (SBP)

Change from baseline in SBP was analyzed by overall response (CR+PR, SD+PD). (NCT01201265)
Timeframe: Baseline, Cycle 6, 12 of treatment

Interventionmillimetre of mercury (mmHg) (Mean)
Baseline; CR+PR (n= 19)Change at cycle 6; CR+PR (n=14)Change at cycle 12; CR+PR at cycle 12 (n=5)Baseline; SD+PD (n= 18)Change at cycle 6; SD+PD at cycle 6 (n=13)Change at cycle 12; SD+PD at cycle 12 (n=4)
All Participants124.8-4.6-4.0123.60.2-6.3

[back to top]

Change From Baseline in Diastolic Blood Pressure (DBP)

Change from baseline in DBP was analyzed by overall response (CR+PR, SD+PD). (NCT01201265)
Timeframe: Baseline, Cycle 6, 12 of treatment

InterventionmmHg (Mean)
Baseline; CR+PR (n= 19)Change at cycle 6; CR+PR (n=14)Change at cycle 12; CR+PR (n=5)Baseline; SD+PD (n= 18)Change at cycle 6; SD+PD (n=13)Change at cycle 12; SD+PD (n=4)
All Participants80.4-4.1-2.078.92.37.5

[back to top]

Time to Progression (TTP)

Duration of time to progression (TTP) was estimated using the Kaplan-Meier method. The time to progression was calculated in days from the date of registration until the earliest date of documented disease progression. (NCT01201265)
Timeframe: From the date of registration until the disease progression (up to 1541 days).

Interventiondays (Median)
All Participants269.0

[back to top]

Number of Participants With an Adverse Event (AE)

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. (NCT01201265)
Timeframe: Up to 28 days after termination of study treatment (approximately 1569 days)

Interventionparticipants (Number)
All Participants24

[back to top]

Overall Survival (OS)

Overall survival was measured from the date of the first study drug dose to the date of death from any cause. The median overall survival time with 95%CI was estimated using Kaplan-Meier method. (NCT01201265)
Timeframe: From the date of registration until the disease progression or death (up to 1541 days)

Interventiondays (Median)
All Participants475.0

[back to top]

Percentage of Participants Achieving an Overall Response

The overall response rate (ORR) was defined as complete response (CR) + partial response (PR). ORR was summarized using number and percentage along with two-sided 95% Pearson-Clopper CI. The overall response rate was assessed utilizing the RECIST v. 1.1. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30% decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. (NCT01201265)
Timeframe: From the date of registration until the disease progression or death (up to 1541 days)

Interventionpercentage of participants (Number)
All Participants50.0

[back to top]

Progression-free Survival (PFS)

The length of time during and after study treatment that participants lived with disease that did not progress per RECIST 1.0. Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir. (NCT01218048)
Timeframe: Up to 54 months

Interventionmonths (Median)
Neo-Adjuvant Cetuximab24

[back to top]

Frequency of EGFR-specific T Cells (EGFR853-861 Peptide-specific Tetramer+ CD8+T Cells)

Difference in frequency of circulating EGFR-specific T cells between cetuximab-treated and cetuximab-naive patients (NCT01218048)
Timeframe: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

InterventionEGFR+ T cells/10^4 T cells (Mean)
no cetuximab-treatmentcetuximab-treatment
Neo-Adjuvant Cetuximab45120

[back to top]

T Cell Activation

T cell activation measured at pre-/post-cetuximab exposure (NCT01218048)
Timeframe: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Interventionpercentage of T cell activation (Median)
Pre-cetuximabPost-cetuximab
Neo-Adjuvant Cetuximab0.251.0

[back to top]

Change in Tumor Size

Largest percent change (decrease) in tumor size before and after neoadjuvant cetuximab. (NCT01218048)
Timeframe: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Interventionpercent (Number)
Neo-Adjuvant Cetuximab10

[back to top]

Serum Cytokines Levels

Serum cytokines levels measured at pre-/post-cetuximab, exposure measured in picogram per milliliter of plasma (pg/ml) (NCT01218048)
Timeframe: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Interventionpg/ml (Median)
Responders: pre-cetuximab GM-CSFNon-responders: pre-cetuximab GM-CSFResponders: post-cetuximab GM-CSFNon-responders: post-cetuximab GM-CSFResponders: pre-cetuximab CCL2Non-responders: pre-cetuximab CCL2Responders: post-cetuximab CCL2Non-responders: post-cetuximab CCL2Responders: pre-cetuximab MP-1 alphaNon-responders: pre-cetuximab MP-1 alphaResponders: post-cetuximab MP-1 alphaNon-responders: post-cetuximab MP-1 alpha
Neo-Adjuvant Cetuximab2.518.011.05.02605002502006.010.07.03.0

[back to top]

Overall Survival (OS)

Number of patients remaining alive. (NCT01218048)
Timeframe: Up to 2 years

Interventionparticipants (Number)
Neo-Adjuvant Cetuximab40

[back to top]

Objective Response (Rate)

The percentage of participants that experienced a response to study treatment, per RECIST 1.0: Number of participant with (Complete Response (CR) + number of participants with Partial Response (PR) / Total number of participants evaluable for response. (NCT01218048)
Timeframe: Up to 2 years

Interventionpercentage of participants (Number)
Neo-Adjuvant Cetuximab33

[back to top]

3-year Progression-free Survival (PFS)

Percentage of participants alive at 3 years that did not experience disease progression per RECIST 1.0. Progression per RECIST 1.0 is defined as a 20% increase the in longest dimension (LD) lesion from Nadir. (NCT01218048)
Timeframe: 3 years

Interventionpercentage of participants (Number)
Neo-Adjuvant Cetuximab84

[back to top]

NK Cell Activation

Cetuximab-mediated NK cell activation (percentage of activity) measures at pre-/post-cetuximab exposure for patients in peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL) and in those patients that did and did not respond to treatment. (NCT01218048)
Timeframe: Prior to each weekly cetuximab treatment (up to 4 weeks); at the time of surgery (at 3-4 weeks after first cetuximab treatments)

Interventionpercentage of activity (Median)
Percent NK cells (PBL): pre-cetuximabPercent NK cells (PBL): post-cetuximabPercent NK cells (TIL): pre-cetuximabPercent NK cells (TIL): post-cetuximabPercent CD16+ NK cells(PBL): pre-cetuximabPercent CD16+ NK cells (PBL): post-cetuximabPercent CD16+ NK cells (TIL): pre-cetuximabPercent CD16+ NK cells (TIL): post-cetuximabPercent Granzyme B+ cells (PBL): pre-cetuximabPercent Granzyme B+ cells(PBL): post-cetuximabPercent Granzyme B+ cells (TIL): pre-cetuximabPercent Granzyme B+ cells (TIL): post-cetuximabPercent Perforin+ cells (PBL): pre-cetuximabPercent Perforin+ cells (PBL): post-cetuximabPercent Perforin+ cells (TIL): pre-cetuximabPercent Perforin+ cells (TIL): post-cetuximabPercent CD107a+ cells (PBL): pre-cetuximabPercent CD107a+ cells (PBL): post-cetuximabPercent CD107a+ cells (TIL): pre-cetuximabPercent CD107a+ cells (TIL): post-cetuximabPercent CD137+ cells (PBL): pre-cetuximabPercent CD137+ cells (PBL): post-cetuximabPercent CD137+ cells (TIL): pre-cetuximabPercent CD137+ cells (TIL): post-cetuximab
Neo-Adjuvant Cetuximab192043554910654641721506061010366020610

[back to top]

Duration of Response (DR)

DR was derived for those participants with objective evidence of CR or PR. DR was defined as the time (in months) from first documentation of objective response (CR or PR) to the first documentation of disease progression (ie, objective tumor progression as assessed by investigator's radiology review or other protocol-approved measures of disease progression) or death due to any cause. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT01218516)
Timeframe: From the first documentation of objective response (CR or PR) to the first documentation of disease progression, death due to any cause, or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis

InterventionMonths (Median)
Combination Therapy: Placebo + Chemotherapy6.7
Combination Therapy: Farletuzumab + Chemotherapy4.1

[back to top]

Overall Survival (OS)

OS was defined as the time (in months) from the date of randomization to the date of death, regardless of cause. (NCT01218516)
Timeframe: From the date of randomization to the date of death due to any cause or up to cut-off date of 1 Nov 2013 (up to approximately 28 months) for final analysis

InterventionMonths (Median)
Combination Therapy: Placebo + Chemotherapy10.5
Combination Therapy: Farletuzumab + Chemotherapy14.1

[back to top]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (SAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered with an investigational product. A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose; resulted in death, was life-threatening (i.e., the participant was at a risk of death at the time of the event; this did not include an event that hypothetically might have caused death if it had been more severe), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions, or was a congenital abnormality/birth defect. In this study, TEAEs (defined as an AE that started/increased in severity on/after the first dose of study medication up to 30 days after the final dose of study medication) were assessed. (NCT01218516)
Timeframe: For each participant, from the first dose till 30 days after the last dose or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis

,,,
InterventionParticipants (Count of Participants)
TEAEsTreatment emergent SAEs
Combination Therapy: Farletuzumab + Chemotherapy6327
Combination Therapy: Placebo + Chemotherapy6027
Monotherapy: Farletuzumab257
Monotherapy: Placebo306

[back to top]

Overall Response Rate (ORR)

ORR, defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) as determined by investigator's radiologic assessments using RECIST 1.1 for target lesions and assessed by Magnetic resonance imaging (MRI) and computerized tomography (CT) scan (for double blind treatment period i.e. Randomization Phase). CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to less than 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR. (NCT01218516)
Timeframe: From Day 1 until documented radiographic progression, other protocol-approved measures of disease progression, withdrawal by participant, death due to any cause, or cut-off date of 1 Nov 2013, i.e., up to approximately 28 months for final analysis

InterventionPercentage of participants (Number)
Combination Therapy: Placebo + Chemotherapy37.3
Combination Therapy: Farletuzumab + Chemotherapy41.3

[back to top]

Progression-free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of the first observation of investigator-assessed (radiology review) progression based on Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 or other protocol-approved measures of disease progression (e.g., new occurrence of positive fluid cytology, newly diagnosed evidence of disease progression from histologic samples, PET-positive metastases, or new bone or brain metastases), or date of death, whatever the cause. Disease progression as assessed by the investigator per RECIST v1.0 was defined as at least a 20% increase in sum of longest diameters (RECIST definition) compared to baseline (or lowest sum while on study if less than baseline), or any new lesions (measurable or nonmeasurable). (NCT01218516)
Timeframe: From date of first administration of study drug up to 6 month follow-up from randomization of the last participant, i.e., cut-off date 15 Dec 2012 for primary analysis and cut-off date of 1 Nov 2013 or up to approximately 28 months for final analysis

,
InterventionMonths (Median)
Per Primary Analysis Cut-Off DatePer Final Analysis Cut-Off Date
Combination Therapy: Farletuzumab + Chemotherapy4.74.7
Combination Therapy: Placebo + Chemotherapy5.85.9

[back to top]

Tolerated Dose

To determine the maximum tolerated dose of carboplatin AUC5 administered Day 1 Cycles 1-4, weekly paclitaxel 60-80mg/m2 administered on Day 1, 8,and 15 for 3 weeks cycles 1-4, bevacizumab 15mg/kg administered Day 1 Cycles 1-3 prior to surgical intervention. (NCT01219777)
Timeframe: Up to 6 months

Interventionmg/m^2 (Number)
Arm I80

[back to top]

Toxicity and Response Rates Based on Imaging and Surgical Outcomes

Determine the safety/toxicity of this regimen in this patient population. Estimate the percent of patients undergoing successful cytoreductive surgery to optimal disease (<1 cm greatest tumor diameter) following neoadjuvant chemotherapy with carboplatin, paclitaxel and bevacizumab in patients with epithelial ovarian cancer, primary peritoneal cancer and fallopian tube cancer. Assess the 30 day morbidity and mortality following surgical intervention. To describe the response rate for patients treated with neoadjuvant carboplatin, weekly paclitaxel, and bevacizumab using RECIST and GCIG response criteria prior to surgical intervention. Response was determined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01219777)
Timeframe: Up to 6 months

Interventionpatients (Number)
Partial ResponsesDose Limiting ToxicitiesOptimal debulking achieved
Arm I909

[back to top]

Number of Subjects With Alanine Aminotransferase Increased Abnormality, by Common Terminology Criteria for Adverse Events (CTCAE) Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1220001
Cohort A-Placebo Group510001
Cohort B-GSK2302024A Group810000
Cohort B-Placebo Group420000
Cohort C-GSK2302024A Group650000
Cohort C-Placebo Group220000
Cohort D-GSK2302024A-D14 Group120005

[back to top]

Number of Subjects With Lymphocyte Count Decreased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group951000
Cohort A-Placebo Group421000
Cohort B-GSK2302024A Group035100
Cohort B-Placebo Group022200
Cohort C-GSK2302024A Group235100
Cohort C-Placebo Group111100
Cohort D-GSK2302024A-D14 Group112004

[back to top]

Number of Subjects With Hyponatremia Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and post 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1500000
Cohort A-Placebo Group600001
Cohort B-GSK2302024A Group540000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1100000
Cohort C-Placebo Group400000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Hypocalcemia Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1230000
Cohort A-Placebo Group600001
Cohort B-GSK2302024A Group531000
Cohort B-Placebo Group411000
Cohort C-GSK2302024A Group1010000
Cohort C-Placebo Group310000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Hypokalemia Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1500000
Cohort A-Placebo Group600001
Cohort B-GSK2302024A Group901000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1010000
Cohort C-Placebo Group400000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Hypoalbuminemia Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1311000
Cohort A-Placebo Group600001
Cohort B-GSK2302024A Group900000
Cohort B-Placebo Group510000
Cohort C-GSK2302024A Group920000
Cohort C-Placebo Group310000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Hypernatremia Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1410000
Cohort A-Placebo Group420001
Cohort B-GSK2302024A Group900000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1001000
Cohort C-Placebo Group400000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Hyperkalemia Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1500000
Cohort A-Placebo Group510001
Cohort B-GSK2302024A Group711000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1010000
Cohort C-Placebo Group400000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Hypercalcemia Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1410003
Cohort A-Placebo Group330001
Cohort B-GSK2302024A Group810000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1100000
Cohort C-Placebo Group400000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Severe Toxicities

Severe toxicity was defined as follows: - A Grade 3 or higher toxicity that is related or possibly related to the combined administration of standard treatment and GSK2302024A/placebo - A decrease in Left Ventricular Ejection Fraction (LVEF) from baseline with ≥ 10 points and at < 50% that is related or possibly related to the combined administration of treatment and that is confirmed by a second LVEF assessment within approximately 3 weeks. - A Grade 2 or higher cardiac ischemia/infarction that is related or possibly related to the combined administration of standard treatment and GSK2302024A /placebo. - A Grade 2 or higher allergic reaction occurring within 24 hours following the administration. - A Grade 3 or higher blood/bone marrow toxicity that was considered as related or possibly related to the combined Administration. - A decrease in renal function at the time of administration that was considered as related or possibly related. (NCT01220128)
Timeframe: From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)

InterventionSubjects (Number)
Cohort A-GSK2302024A Group0
Cohort A-Placebo Group0
Cohort B-GSK2302024A Group1
Cohort B-Placebo Group0
Cohort C-GSK2302024A Group1
Cohort C-Placebo Group0
Cohort D-GSK2302024A-D14 Group0

[back to top]

Number of Subjects With Hemoglobin Increased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1500000
Cohort A-Placebo Group610000
Cohort B-GSK2302024A Group900000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1100000
Cohort C-Placebo Group400000
Cohort D-GSK2302024A-D14 Group400004

[back to top] [back to top]

Number of Subjects With Aspartate Aminotransferase Increased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1231000
Cohort A-Placebo Group420001
Cohort B-GSK2302024A Group810000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group740000
Cohort C-Placebo Group130000
Cohort D-GSK2302024A-D14 Group210005

[back to top]

Number of Subjects With White Blood Cell Decreased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1320000
Cohort A-Placebo Group700000
Cohort B-GSK2302024A Group621000
Cohort B-Placebo Group321000
Cohort C-GSK2302024A Group740000
Cohort C-Placebo Group211000
Cohort D-GSK2302024A-D14 Group010304

[back to top]

Number of Patients With an Anti-Wilm's Tumor Gene (Anti-WT1) Humoral Response

For initially seronegative patients: post-administration antibody concentration ≥ 9 EU/mL For initially seropositive patients: post-administration antibody concentration ≥ 2 fold the pre-administration antibody concentration. (NCT01220128)
Timeframe: At post-GSK2302024A/placebo Dose 4 (Week 13)

InterventionSubjects (Number)
Cohort A-GSK2302024A Group10
Cohort A-Placebo Group0
Cohort B-GSK2302024A Group0
Cohort B-Placebo Group0
Cohort C-GSK2302024A Group6
Cohort C-Placebo Group0
Cohort D-GSK2302024A-D14 Group2

[back to top]

Number of Subjects With Anemia, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1221000
Cohort A-Placebo Group700000
Cohort B-GSK2302024A Group170100
Cohort B-Placebo Group040000
Cohort C-GSK2302024A Group074000
Cohort C-Placebo Group031000
Cohort D-GSK2302024A-D14 Group220004

[back to top]

Number of Subjects With Serious Adverse Events (SAEs), by CTCAE Maximum Grade Reported

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Any SAE(s) Grade 1Any SAE(s) Grade 2Any SAE(s) Grade 3Any SAE(s) Grade 4Any SAE(s) Grade 5Any SAE(s)
Cohort A-GSK2302024A Group012003
Cohort A-Placebo Group000000
Cohort B-GSK2302024A Group010214
Cohort B-Placebo Group001102
Cohort C-GSK2302024A Group001405
Cohort C-Placebo Group000101
Cohort D-GSK2302024A-D14 Group001405

[back to top]

Number of Subjects With Creatine Increased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1140004
Cohort A-Placebo Group420001
Cohort B-GSK2302024A Group810000
Cohort B-Placebo Group510000
Cohort C-GSK2302024A Group1010000
Cohort C-Placebo Group310000
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Breast Cancer Pathological Response

The pathological response in lymph nodes was evaluated by presence or absence of tumor cells by histopathological examination. Partial responses mark the disappearance of tumor cells, with only small clusters or dispersed cells remaining (more than 90% loss) while complete response indicate no identifiable malignant cells. However, ductal carcinoma in situ may be present. (NCT01220128)
Timeframe: During the treatment period, up to Week 26/32

,,,,,,
InterventionSubjects (Number)
Partial resposeComplete response
Cohort A-GSK2302024A Group40
Cohort A-Placebo Group30
Cohort B-GSK2302024A Group50
Cohort B-Placebo Group32
Cohort C-GSK2302024A Group36
Cohort C-Placebo Group13
Cohort D-GSK2302024A-D14 Group31

[back to top]

Number of Subjects With Serious Adverse Events SAE(s)

A serious adverse event (SAE) is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of hospitalization, causes disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study patient. In this study, an event which was part of the natural course of the disease under study (i.e., disease progression/recurrence) was captured in the study/as an efficacy measure. Therefore it was not reported as an SAE. Progression/recurrence of the tumor was recorded in the clinical assessments in the electronic case report form (eCRF). Death due to progressive disease was recorded on a specific form in the eCRF but not as an SAE. (NCT01220128)
Timeframe: From Week 0 to Week 26/32 (period starting from GSK2302024A/placebo treatment allocation and ending with the concluding Visit i.e.: Week 26 for patients receiving 6 injections and Week 32 for patients receiving 8 injections)

InterventionSubjects (Number)
Cohort A-GSK2302024A Group3
Cohort A-Placebo Group0
Cohort B-GSK2302024A Group4
Cohort B-Placebo Group2
Cohort C-GSK2302024A Group5
Cohort C-Placebo Group1
Cohort D-GSK2302024A-D14 Group5

[back to top]

Number of Subjects With Platelet Count Decreased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1410000
Cohort A-Placebo Group610000
Cohort B-GSK2302024A Group810000
Cohort B-Placebo Group510000
Cohort C-GSK2302024A Group551000
Cohort C-Placebo Group220000
Cohort D-GSK2302024A-D14 Group220004

[back to top]

Number of Subjects With Neutrophil Count Decreased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1230000
Cohort A-Placebo Group601000
Cohort B-GSK2302024A Group711000
Cohort B-Placebo Group510000
Cohort C-GSK2302024A Group1010000
Cohort C-Placebo Group300100
Cohort D-GSK2302024A-D14 Group001034

[back to top]

Number of Patients With Adverse Events (AEs), by CTCAE Maximum Grade Reported

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Any AE(s) Grade 1Any AE(s) Grade 2Any AE(s) Grade 3Any AE(s) Grade 4Any AE(s) Grade 5Any AE(s)
Cohort A-GSK2302024A Group6630015
Cohort A-Placebo Group140005
Cohort B-GSK2302024A Group060219
Cohort B-Placebo Group005106
Cohort C-GSK2302024A Group0434011
Cohort C-Placebo Group030104
Cohort D-GSK2302024A-D14 Group021407

[back to top] [back to top]

Number of Subjects With Lymphocyte Count Increased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1500000
Cohort A-Placebo Group700000
Cohort B-GSK2302024A Group900000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1100000
Cohort C-Placebo Group400000
Cohort D-GSK2302024A-D14 Group400004

[back to top]

Number of Subjects With Blood Bilirubin Increased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1500000
Cohort A-Placebo Group510001
Cohort B-GSK2302024A Group900000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group1100000
Cohort C-Placebo Group201100
Cohort D-GSK2302024A-D14 Group300005

[back to top]

Number of Subjects With Alkaline Phosphatase Increased Abnormality, by CTCAE Maximum Grade

Criteria for Adverse Events (CTCAE), version 4.0 of May 28, 2009. Grades refer to the severity of the AE: mild (grade 1), moderate (grade 2), severe or medically significant (grade 3), life-threatening (grade 4) and death (grade 5). (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

,,,,,,
InterventionSubjects (Number)
Grade 0Grade 1Grade 2Grade 3Grade 4Grade Unknown
Cohort A-GSK2302024A Group1050000
Cohort A-Placebo Group510001
Cohort B-GSK2302024A Group810000
Cohort B-Placebo Group600000
Cohort C-GSK2302024A Group740000
Cohort C-Placebo Group310000
Cohort D-GSK2302024A-D14 Group120005

[back to top]

Number of Patients With Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e., lack of efficacy), abuse or misuse. (NCT01220128)
Timeframe: During the treatment period and up to 30 days post last administration

InterventionSubjects (Number)
Cohort A-GSK2302024A Group15
Cohort A-Placebo Group5
Cohort B-GSK2302024A Group9
Cohort B-Placebo Group6
Cohort C-GSK2302024A Group11
Cohort C-Placebo Group4
Cohort D-GSK2302024A-D14 Group7

[back to top]

4-y Overall Survival Rate

4-year overall survival rate is the percentage of patients remaining alive 4-years from study entry. (NCT01221753)
Timeframe: Patients were followed for survival up to 5 years from study entry. Patients alive have been followed for a mean of 55 months (range 52-60 months).

Interventionpercentage of participants (Number)
TPF Induction Chemotherapy Followed by Chemoradiotherapy100

[back to top]

Overview of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

To assess the type and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs). An AE was defined as any noxious, pathologic, or unintended change un anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of the study, whether or not deemed study drug-related. An SAE was any AE resulting in death, life-threatening experience, initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, or congenital defect. All AEs were reported from the time of the first dose of study treatment until 28 days after the final dose of study drug. the severity of AEs were graded by the Investigator using National cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) version 4.0. (NCT01237678)
Timeframe: From the first dose of study drug on Cycle 1, Day 1 until 28 days after the last study treatment (up to 22 months)

,,
Interventionparticipants (Number)
Any TEAERelated TEAEAny SAERelated SAETEAEs leading to discontinuationAny Grade ≥ 3 TEAERelated Grade ≥ 3 TEAEDeaths within 28 days of last dose
Phase I - IMGN901 + Carboplatin + Etoposide3332168829221
Phase II - Carboplatin + Etoposide4639239642335
Phase II - IMGN901 + Carboplatin + Etoposide9490543050928314

[back to top]

Occurrence of Dose Limiting Toxicities (DLT)

The primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) and characterize the dose limiting toxicities (DLT) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. For the purposes of dose escalation and determination of MTD, DLTs were defined as AEs or abnormal laboratory values related to study treatment which occurred in Cycle 1 of the Dose Escalation phase, including any AEs that resulted in failure to meet the criteria for re-treatment. The following events were considered DLTs (using the most current version of CTCAE): febrile neutropenia; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding; ≥ Grade 3 peripheral neuropathy; ≥ Grade 3 vomiting, nausea, or diarrhea that persisted despite the use of optimal therapy; other ≥ grade 3 non-hematologic toxicity (with the exception of brief fatigue i.e. ≤ 72 hours and alopecia) (NCT01237678)
Timeframe: 21 days (Cycle 1)

,,,,
Interventionparticipants (Number)
Grade 3 febrile neutropeniaGrade 4 febrile neutropeniaGrade 4 thrombocytopeniaGrade 4 granulocytopeniaGrade 3 lobar pneumonia
IMGN901 112 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m200101
IMGN901 60 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m201000
IMGN901 75 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m200000
IMGN901 75 mg/m2 + Carboplatin AUC 6 + Etoposide 100 mg/m211210
IMGN901 90 mg/m2 + Carboplatin AUC 5 + Etoposide 100 mg/m201100

[back to top]

Progression Free Survival (PFS) Rate at 6 Months

The trial was not empowered to permit a statistically informative comparison of the randomized treatment groups with respect to PFS. The activity of IMGN901 was assessed by comparing the PFS rate at 6 months in the IMGN901 experimental arm against the historical 6-month PFS rate of 0.44 (equivalently a median PFS = 5 months). Only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented as the objective was to compare PFS at 6 months in the experimental arm (triplet combination) against the historical PFS rate of 0.44 (equivalently a median PFS = 5 months) for carboplatin and etoposide. The control arm was planned primarily to reliably assess the safety of IMGN901 and to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed. (NCT01237678)
Timeframe: 6 months

Interventionpercentage of participants (Number)
Phase II - IMGN901 + Carboplatin + Etoposide39

[back to top]

Progression Free Survival (PFS) in Phase II

The primary outcome measure for Phase II was to determine the efficacy of IMGN901 in combination with carboplatin/etoposide chemotherapy as first-line treatment for patients with extensive stage small cell lung cancer. PFS was defined as the time from enrollment until objective tumor progression according to RECIST 1.1 or death on study due to any cause, whichever occurred first. Only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented as the primary objective of this phase of the study was to compare PFS in the experimental arm (triplet combination) against historical PFS rates for carboplatin and etoposide. The control arm was planned primarily to reliably assess the safety of IMGN901 and to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed. (NCT01237678)
Timeframe: From randomization to objective tumor progression or death (up to post-treatment follow-up 28 days after last dose, up to 22 months)

Interventionmonths (Median)
Phase II - IMGN901 + Carboplatin + Etoposide6.2

[back to top]

Overall Survival (OS) Rate at 12 Months

OS was analyzed based on a binary definition of the number of patients dead or censored prior to 12 months and the number of patients alive at 12 months. The primary objective of this phase of the study was to compare PFS in the experimental arm (triplet combination) against historical PFS rates. The control arm was primarily planned to demonstrate whether the or not the historical assumptions regarding efficacy were confirmed. Further, the trial was not empowered to permit a statistically informative comparison of the randomized treatment groups with respect to OS and no determination of the OS rate at 12 months for the control arm was performed; therefore only the results from the experimental arm (IMGN901 + carboplatin + etoposide) are presented. (NCT01237678)
Timeframe: 12 months

Interventionpercentage of participants alive (Number)
Phase II - IMGN901 + Carboplatin + Etoposide61

[back to top]

Median Overall Survival (OS) in Phase II

A secondary outcome measure for Phase II was to determine the overall survival of patients treated with IMGN901 in combination with carboplatin/etoposide chemotherapy versus carboplatin/etoposide chemotherapy alone as first-line treatment for patients with extensive stage small cell lung cancer. (NCT01237678)
Timeframe: From the time of enrollment until death on study due to any cause (up to post-treatment follow-up 28 days after last dose, up to 22 months)

Interventionmonths (Median)
Phase II - IMGN901 + Carboplatin + Etoposide10.1
Phase II - Carboplatin + Etoposide10.97

[back to top]

Maximum Tolerated Dose (MTD) of IMGN901

A primary outcome measure for Phase I was to determine the maximum tolerated dose (MTD) of IMGN901 when administered in combination with carboplatin/etoposide chemotherapy followed by IMGN901 alone in patients with solid tumors. The MTD was determined based on DLTs that occurred during Cycle 1. (NCT01237678)
Timeframe: 21 days (Cycle 1)

Interventionmg/m^2 (Number)
Phase I - IMGN901 + Carboplatin + Etoposide112

[back to top]

Percentage of Participants Achieving Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST Version 1.0

Best overall response (BOR) according to RECIST Version 1.0 was categorized as: CR, PR, progressive disease (PD), stable disease (SD). CR: disappearance of all target lesions and non-target lesions. PR: >=30% decrease in sum of the longest diameters (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non-target lesions. PD: Natural progression or deterioration of the malignancy under study (including new sites of metastasis). SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum longest diameter since the treatment started. Participants with a BOR of CR and PR were defined as responders, while participants with a BOR of SD, PD, or unable to assess were defined as non-responders. (NCT01239732)
Timeframe: Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks (Q26W) after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 years

Interventionpercentage of participants (Number)
Bevacizumab + Paclitaxel + Carboplatin72.7

[back to top]

Percentage of Participants Achieving an Overall Response by 50% Carcinoma Antigen 125 (CA-125) Response Criteria

CA-125 responders: Participants with the value of CA-125 reduced by at least 50% and confirmed with a consecutive CA-125 assessment performed at an interval of at least 28 days. Overall response according to CA-125 was only evaluated for participants with a pre-treatment CA-125 within 3 days prior to start of any study treatment of at least twice the upper limit of normal (ULN). (NCT01239732)
Timeframe: 3 days prior to Day 1 of every cycle, then every 6 weeks (Q6W) during the first year, every 3 months (Q3M) in the second and third year, every 6 months (Q6M) in the fourth year of the study (until data cutoff 07 December 2014, up to 4 years)

Interventionpercentage of participants (Number)
Bevacizumab + Paclitaxel + Carboplatin91.8

[back to top]

Overall Survival (OS)

OS was defined as the time from the date of the first administration of any study treatment to the date of death, regardless of the cause of death. Participants without the event of death were censored at the last date in the study, defined as the latest date of the following: the date of first administration of study treatment, date of last study treatment, date of last visit, or date last known to be alive. Kaplan-Meier estimation was used for OS. (NCT01239732)
Timeframe: First administration of any study treatment until death or data cutoff 07 December 2014, up to 4 years

Interventionmonths (Median)
Bevacizumab + Paclitaxel + CarboplatinNA

[back to top]

Duration of Objective Response (DOR)

DOR was defined as the time from the first documented response (CR or PR per RECIST v1.0), to the first documented protocol-defined disease progression (i.e., radiologically by RECIST, clinical, or symptomatic) or death, whichever occurred first. Participants who had neither progressed nor died at the time of data cut-off (07 December 2014), or participants who were withdrawn from study, or lost to follow-up without documented progression, were censored. RECIST responders: Participants achieving an overall response of CR (disappearance of all target lesions and non-target lesions) or PR (>=30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non-target lesions). Disease progression: Natural progression or deterioration of the malignancy under study (including new sites of metastasis). (NCT01239732)
Timeframe: Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 years

Interventionmonths (Median)
Bevacizumab + Paclitaxel + Carboplatin18.2

[back to top]

Progression-Free Survival (PFS)

PFS was defined as the time between the date of first administration of any study treatment and the date of first documented protocol-defined disease progression (that is [i.e.], radiologically by Response Evaluation Criteria In Solid Tumors [RECIST], clinical, or symptomatic) or death, whichever occurred first. Participants who had neither progressed nor died at the time of data cut-off (07 December 2014), or participants who were withdrawn from study, or lost to follow-up without documented progression, were censored. Kaplan-Meier estimation was used for median time to PFS. (NCT01239732)
Timeframe: Day 1, at end of Cycles 3 and 6, then every 6 cycles while receiving bevacizumab, and then at bevacizumab cessation, every 26 weeks after cessation of bevacizumab until disease progression or death until data cutoff 07 December 2014, up to 4 years

Interventionmonths (Median)
Bevacizumab + Paclitaxel + Carboplatin25.5

[back to top]

Percentage of Participants With at Least One Adverse Event (AE)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. (NCT01239732)
Timeframe: Day 1 up to 30 days after last dose of study treatment (until data cutoff 07 December 2014, up to 4 years)

Interventionpercentage of participants (Number)
Bevacizumab + Paclitaxel + Carboplatin97.8

[back to top]

Percentage of Participants Achieving an Overall Response by RECIST Version 1.0 and/or 50% CA-125 Response Criteria

Overall response was only evaluated for participants who were evaluable according to RECIST v1.0 with a measurable disease at baseline and/or according to CA-125 with a pre-treatment CA-125 within 3 days prior to start of any study treatment of at least twice the ULN. RECIST responders: Participants achieving an overall response of CR (disappearance of all target lesions and non-target lesions) or PR (>=30% decrease in sum of the LD of the target lesions taking as a reference the baseline sum LD according to RECIST associated to non-progressive disease response for non target lesions). CA-125 responders: Participants with the value of CA-125 reduced by at least 50% and confirmed with a consecutive CA-125 assessment performed at an interval of at least 28 days. (NCT01239732)
Timeframe: RECIST: Day 1, at end of Cycles 3 and 6, then every 6 cycles, at bevacizumab cessation, Q26W after cessation; CA-125: 3 days before Day 1 of every cycle, then Q6W(1st year), Q3M(2nd-3rd year), Q6M(4th year); until data cutoff 07Dec2014, up to 4 years

Interventionpercentage of participants (Number)
Bevacizumab + Paclitaxel + Carboplatin82.4

[back to top]

Number of Participants With a Decline in Karnofsky Performance Status (KPS) of ≥ 20 Points at Worst Record On-study Compared With Baseline

KPS scale: 100 is no evidence of disease; 90 is able to carry on normal activity, minor symptoms of disease; 80 is normal activity with effort, some symptoms of disease; 70 is cares for self; unable to do active work; 60 is requires occasional assistance, but is able to care for most of his needs; 50 is requires considerable assistance with frequent medical care; 40 is disabled, requires special care; 30 is severely disabled, hospitalization is indicated although death is not imminent; 20 is very sick, hospitalization necessary, active support treatment necessary; 10 is moribund, fatal processes progressing rapidly, 0 is dead. (NCT01248949)
Timeframe: From start of study drug administration up to 30 days after the last dose of MEDI3617

InterventionParticipants (Number)
MEDI3617 SINGLE AGENT TOTAL11
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL6
MEDI3617 + BEVACIZUMAB Q2W TOTAL7
MEDI3617 + PACLITAXEL TOTAL1
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL1

[back to top]

Number of Participants With Dose Limiting Toxicities (DLTs)

DLT was defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617. (NCT01248949)
Timeframe: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)

InterventionParticipants (Number)
MEDI3617 SINGLE AGENT TOTAL1
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL1
MEDI3617 + BEVACIZUMAB Q2W TOTAL2
MEDI3617 + PACLITAXEL TOTAL1
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL1

[back to top]

Number of Participants With Echocardiogram Abnormalities Recorded as Adverse Events (AEs)

An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to echocardiogram abnormalities were recorded and reported. The only AE reported was ejection fraction decreased in the MEDI3617 + Paclitaxel total group. (NCT01248949)
Timeframe: From start of study drug administration up to 90 days after the last dose of MEDI3617

InterventionParticipants (Number)
MEDI3617 SINGLE AGENT TOTAL0
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL0
MEDI3617 + BEVACIZUMAB Q2W TOTAL0
MEDI3617 + PACLITAXEL TOTAL1
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL0

[back to top]

Number of Participants With Electrocardiogram Abnormalities Recorded as Adverse Events (AEs)

An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to electrocardiogram abnormalities were recorded and reported. The only AE reported was electrocardiogram QT prolonged in the MEDI3617 + Bevacizumab Q2W total group. (NCT01248949)
Timeframe: From start of study drug administration up to 90 days after the last dose of MEDI3617

InterventionParticipants (Number)
MEDI3617 SINGLE AGENT TOTAL0
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL0
MEDI3617 + BEVACIZUMAB Q2W TOTAL1
MEDI3617 + PACLITAXEL TOTAL0
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL0

[back to top]

Number of Participants With Positive Anti-Drug Antibody (ADA)

The immunogenic potential of MEDI3617 was assessed by summarizing the number and percentage of participants who develop detectable ADA. Immunogenicity assessment included determination of anti-drug (MEDI3617) antibodies in serum samples. Samples were measured for the presence of ADA using validated immunoassays. (NCT01248949)
Timeframe: Presence of ADA to MEDI3617 were assessed prior to infusion with MEDI3617 on Day 1 of each dosing cycle, as well as the end of treatment, and 30 days, 3 months, and 6 months post last dose of MEDI3617

Interventionparticipants (Number)
MEDI3617 SINGLE AGENT TOTAL0
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL0
MEDI3617 + BEVACIZUMAB Q2W TOTAL0
MEDI3617 + PACLITAXEL TOTAL0
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL0

[back to top]

Time to Progression (TTP)

Time to progression (TTP) is defined as time from the start of treatment with MEDI3617 until the documentation of disease progression. The TTP was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had TTP censored on the first date of treatment with MEDI3617. TTP was evaluated using the Kaplan-Meier method. (NCT01248949)
Timeframe: Time from the first dose of investigational product until end of study

Interventionmonths (Median)
MEDI3617 SINGLE AGENT TOTAL1.4
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL11.4
MEDI3617 + BEVACIZUMAB Q2W TOTAL1.8
MEDI3617 + PACLITAXEL TOTAL3.5
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNA

[back to top]

Number of Participants With Vital Sign Abnormalities Recorded as Adverse Events (AEs)

Vital signs included parameters such as heart rate, blood pressure, temperature, weight and respiratory rate. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to vital signs abnormalities were recorded and reported. (NCT01248949)
Timeframe: From start of study drug administration up to 90 days after the last dose of MEDI3617

,,,,
InterventionParticipants (Number)
ArrhythmiaSinus tachycardiaTachycardiaPyrexiaWeight decreasedWeight increasedHypertensionHypotension
MEDI3617 + BEVACIZUMAB Q2W TOTAL000100131
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL01132270
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL00011020
MEDI3617 + PACLITAXEL TOTAL01100130
MEDI3617 SINGLE AGENT TOTAL101309100

[back to top]

Systemic Clearance (CL) of MEDI3617

"Systemic clearance describes the removal of drug from a volume of serum in a given unit of time (drug loss from the body). It is measured as milliliter per day (mL/day). Here, n is number of participants analyzed for this endpoint at a specific dose." (NCT01248949)
Timeframe: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose

,,,,
Interventionmilliliter per day (mL/day) (Mean)
Cohort -2 (n=1)Cohort 1 (n=1)Cohort 2 (n=2)Cohort 3 (n=3)Cohort 4 (n=2)Cohort 5 (n=2)Cohort OCE -1 (n=12)Cohort OCE 1 (n=2)Cohort MB 1A (n=3)Cohort MB 2A (n=3)Cohort MB 4A (n=2)Cohort MB 1B (n=7)Cohort MB 2B (n=3)Cohort MB 3B(n=2)Cohort MB 4B (n=1)Cohort MP1 (n=3)Cohort MP2 (n=1)Cohort MCP1 (n=1)Cohort MCP2 (n=2)
MEDI3617 + BEVACIZUMAB Q2W TOTALNANANANANANANANANANANA797847501216NANANANA
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNANANANANANANANA1060614388NANANANANANANANA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNANANANANANANANANANANANANANANANANA446424
MEDI3617 + PACLITAXEL TOTALNANANANANANANANANANANANANANANA727356NANA
MEDI3617 SINGLE AGENT TOTAL27902460423679465355352603NANANANANANANANANANANA

[back to top]

Overall Survival (OS)

Overall survival is defined as the time from the start of treatment with MEDI3617 until death. For the participants who were alive at the end of study or lost to follow-up, overall survival was censored on the last date when participants were known to be alive. Overall survival was evaluated using the Kaplan-Meier method. (NCT01248949)
Timeframe: Time from the first dose of investigational product until death due to any cause

Interventionmonths (Median)
MEDI3617 SINGLE AGENT TOTAL11.4
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL25.7
MEDI3617 + BEVACIZUMAB Q2W TOTAL7.4
MEDI3617 + PACLITAXEL TOTAL14.2
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNA

[back to top]

Progression-Free Survival (PFS)

PFS was measured from the start of treatment with MEDI3617 until the documentation of disease progression or death due to any cause, whichever occurred first. PFS was censored on the date of last tumor assessment documenting absence of tumor progression for participants who have no documented progression and were still alive prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Participants having no tumor assessments after the start of treatment with MEDI3617 had PFS censored on the first date of treatment with MEDI3617. PFS was evaluated using the Kaplan-Meier method. (NCT01248949)
Timeframe: Time from the first dose of investigational product until end of study

Interventionmonths (Median)
MEDI3617 SINGLE AGENT TOTAL1.4
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL11.4
MEDI3617 + BEVACIZUMAB Q2W TOTAL1.7
MEDI3617 + PACLITAXEL TOTAL3.5
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNA

[back to top]

Duration of Response (DOR)

Duration of response is defined as the duration from the first documentation of objective disease response (ie, confirmed CR or confirmed PR) to the first documented disease progression. The duration of response was censored on the date of last tumor assessment documenting absence of disease progression for participants who have no documented progression prior to data cutoff, dropout, or the initiation of alternate anticancer treatment. Duration of response was evaluated for the subgroup of participants with an objective response using the Kaplan-Meier method. (NCT01248949)
Timeframe: Time from the first dose of investigational product until end of study

Interventionmonths (Median)
MEDI3617 SINGLE AGENT TOTAL3.7
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNA
MEDI3617 + BEVACIZUMAB Q2W TOTALNA
MEDI3617 + PACLITAXEL TOTALNA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNA

[back to top]

Time to Response (TTR)

"Time to response (TTR) is defined as the time from the study entry to the first documentation of confirmed CR or confirmed PR. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be 0 if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Analysis was based on responses confirmed at a repeat assessment made at least 4 weeks after the initial response, with the TTR taken as the first time the response was observed, not the confirmation assessment. TTR was evaluated using the Kaplan-Meier method." (NCT01248949)
Timeframe: Time from the first dose of investigational product until end of study

Interventionmonths (Median)
MEDI3617 SINGLE AGENT TOTAL2.6
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL1.2
MEDI3617 + BEVACIZUMAB Q2W TOTAL2.0
MEDI3617 + PACLITAXEL TOTAL1.7
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNA

[back to top]

Area Under the Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3617

"The AUC0-inf is the Area Under the Concentration-Time Curve From Time Zero to infinity of MEDI3617. Here, n is number of participants analyzed for this endpoint at a specific dose." (NCT01248949)
Timeframe: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose

,,,,
Interventionday*mcg/mL (Mean)
Cohort -2 (n=1)Cohort 1 (n=1)Cohort 2 (n=2)Cohort 3 (n=3)Cohort 4 (n=2)Cohort 5 (n=2)Cohort OCE -1 (n=12)Cohort OCE 1 (n=2)Cohort MB 1A (n=3)Cohort MB 2A (n=3)Cohort MB 4A (n=2)Cohort MB 1B (n=7)Cohort MB 2B (n=3)Cohort MB 3B (n=2)Cohort MB 4B (n=1)Cohort MP1 (n=3)Cohort MP2 (n=1)Cohort MCP1 (n=1)Cohort MCP2 (n=2)
MEDI3617 + BEVACIZUMAB Q2W TOTALNANANANANANANANANANANA10425212004630NANANANA
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNANANANANANANANA1106283920NANANANANANANANA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNANANANANANANANANANANANANANANANANA22403560
MEDI3617 + PACLITAXEL TOTALNANANANANANANANANANANANANANANA8492810NANA
MEDI3617 SINGLE AGENT TOTAL1.798.122695292150423032802490NANANANANANANANANANANA

[back to top]

Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-last) of MEDI3617

"AUC0-last is the Area Under the Concentration-Time Curve From Time Zero to the Time of the Last Quantifiable Concentration of MEDI3617. Here, n is number of participants analyzed for this endpoint at a specific dose." (NCT01248949)
Timeframe: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose

,,,,
Interventionday*mcg/mL (Mean)
Cohort -2 (n=3)Cohort -1 (n=2)Cohort 1 (n=6)Cohort 2 (n=3)Cohort 3 (n=3)Cohort 4 (n=3)Cohort 5 (n=4)Cohort OCE -1 (n=15)Cohort OCE 1 (n=2)Cohort MB 1A (n=4)Cohort MB 2A (n=3)Cohort MB 3A (n=3)Cohort MB 4A (n=6)Cohort MB 1B (n=7)Cohort MB 2B (n=3)Cohort MB 3B (n=8)Cohort MB 4B (n=8)Cohort TT2A (n=9)Cohort MP1 (n=7)Cohort MP2 (n=6)Cohort MCP1 (n=4)Cohort MCP2 (n=3)
MEDI3617 + BEVACIZUMAB Q2W TOTALNANANANANANANANANANANANANA94.721680523102590NANANANA
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNANANANANANANANANA10147322802710NANANANANANANANANA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNANANANANANANANANANANANANANANANANANANANA12402890
MEDI3617 + PACLITAXEL TOTALNANANANANANANANANANANANANANANANANANA5511460NANA
MEDI3617 SINGLE AGENT TOTAL1.32.211.91714382610365026102160NANANANANANANANANANANANANA

[back to top]

Circulating Levels of Angiopoietin 2 (Ang2)

Profile of Ang2 post MEDI3617 administration in relation to time course of antibody concentrations. (NCT01248949)
Timeframe: Prior to infusion on Cycle 4 and Cycle 5

,,,,
Interventionnanogram per millileter (ng/mL) (Mean)
Cycle 4: Cohort -2 (n=2)Cycle 5: Cohort -2 (n=2)Cycle 4: Cohort -1 (n=2)Cycle 4: Cohort 1 (n=3)Cycle 5: Cohort 1 (n=2)Cycle 4: Cohort 2 (n=1)Cycle 5: Cohort 2 (n=1)Cycle 4: Cohort 3 (n=1)Cycle 5: Cohort 3 (n=1)Cycle 4: Cohort 4 (n=1)Cycle 4: Cohort 5 (n=1)Cycle 5: Cohort 5 (n=1)Cycle 4: Cohort OCE -1 (n=3)Cycle 5: Cohort OCE -1 (n=3)Cycle 4: Cohort MB 1A (n=2)Cycle 5: Cohort MB 1A (n=2)Cycle 4: Cohort MB 2A (n=3)Cycle 5: Cohort MB 2A (n=2)Cycle 4: Cohort MB 3A (n=1)Cycle 5: Cohort MB 3A (n=2)Cycle 4: Cohort MB 4A (n=4)Cycle 5: Cohort MB 4A (n=2)Cycle 4: Cohort MB 1B (n=2)Cycle 5: Cohort MB 1B (n=1)Cycle 4: Cohort MB 2B (n=1)Cycle 5: Cohort MB 2B (n=1)Cycle 4:Cohort MB 3B (n=1)Cycle 4: Cohort MB 4B (n=3)Cycle 5: Cohort MB 4B (n=1)Cycle 4: Cohort MP1 (n=1)Cycle 4: Cohort MP2 (n=2)Cycle 5: Cohort MP2 (n=2)Cycle 4: Cohort MCP1 (n=2)Cycle 5: Cohort MCP1 (n=2)
MEDI3617 + BEVACIZUMAB Q2W TOTALNANANANANANANANANANANANANANANANANANANANANANA466.27750.61421.03387.45141.93229.19174.65NANANANANA
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNANANANANANANANANANANANANANA386.13421.74215.71228.92218.48247.51368.08353.73NANANANANANANANANANANANA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNANANANANANANANANANANANANANANANANANANANANANANANANANANANANANANANA348.53336.31
MEDI3617 + PACLITAXEL TOTALNANANANANANANANANANANANANANANANANANANANANANANANANANANANANA339.35210.43166.73NANA
MEDI3617 SINGLE AGENT TOTAL4.074.285.115.698.22307.53924.66341.21265.86288.101181.141451.43312.27206.43NANANANANANANANANANANANANANANANANANANANA

[back to top]

Maximum Observed Serum Concentration (Cmax) of MEDI3617

"Cmax is the maximum observed serum concentration of MEDI3617. Here, n is number of participants analyzed for this endpoint at a specific dose." (NCT01248949)
Timeframe: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose

,,,,
Interventionmicrogram per milliliter (mcg/ml) (Mean)
Cohort -2 (n=3)Cohort -1 (n=2)Cohort 1 (n=6)Cohort 2 (n=3)Cohort 3 (n=3)Cohort 4 (n=3)Cohort 5 (n=4)Cohort ovarian cancer expansion (OCE) -1 (n=15)Cohort OCE 1 (n=2)Cohort MB 1A (n=4)Cohort MB 2A (n=3)Cohort MB 3A (n=3)Cohort MB 4A (n=6)Cohort MB 1B (n=7)Cohort MB 2B (n=3)Cohort MB 3B (n=8)Cohort MB 4B (n=8)Cohort TT2A (n=9)Cohort MP1 (n=7)Cohort MP2 (n=6)Cohort MCP1 (n=4)Cohort MCP2 (n=3)
MEDI3617 + BEVACIZUMAB Q2W TOTALNANANANANANANANANANANANANA44.547.5116275320NANANANA
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNANANANANANANANANA30.455.3235348NANANANANANANANANA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNANANANANANANANANANANANANANANANANANANANA200585
MEDI3617 + PACLITAXEL TOTALNANANANANANANANANANANANANANANANANANA114209NANA
MEDI3617 SINGLE AGENT TOTAL1.392.446.6350.282.4239785336346NANANANANANANANANANANANANA

[back to top]

Number of Participants With Laboratory Abnormalities Recorded as Adverse Events (AEs)

Laboratory evaluations were performed, including hematology and serum chemistry. An AE was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. AEs related to laboratory abnormalities were recorded and reported. (NCT01248949)
Timeframe: From start of study drug administration up to 90 days after the last dose of MEDI3617

,,,,
InterventionParticipants (Number)
Hematology: AnemiaHematology: LeukopeniaHematology: NeutropeniaHematology: ThombocytopeniaHematology: White blood cell count decreasedSerChem: Alanine aminotransferase increasedSerChem: Aspartate aminotransferase increasedSerChem: Blood alkaline phosphatase increasedSerChem: Blood creatinine increasedSerChem: Blood lactate dehydrogenase increasedSerChem: Blood potassium increasedSerChem: Blood triglycerides increasedSerChem: Blood urea increasedSerChem: Gamma-glutamyltransferase increasedSerChem: HyperglycaemiaSerChem: HyperkalaemiaSerChem: HypertriglyceridaemiaSerChem: HyperuricaemiaSerChem: HypoalbuminaemiaSerChem: HypocalcaemiaSerChem: HypoglycaemiaSerChem: HypokalaemiaSerChem: HypomagnesaemiaSerChem: Hyponatremia
MEDI3617 + BEVACIZUMAB Q2W TOTAL100001212001110000102201
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL100000101011010011111012
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL223210000000000000000132
MEDI3617 + PACLITAXEL TOTAL310000111100011001000011
MEDI3617 SINGLE AGENT TOTAL501020012000011101001310

[back to top]

Objective Response Rate (ORR)

"Objective response rate defined as the number of participants with confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as disappearance of all target lesions, any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (the sum may not be 0 if there are target nodes). PR was defined as at least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters." (NCT01248949)
Timeframe: Time from the first dose of investigational product until end of study

InterventionParticipants (Number)
MEDI3617 SINGLE AGENT TOTAL1
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL1
MEDI3617 + BEVACIZUMAB Q2W TOTAL2
MEDI3617 + PACLITAXEL TOTAL2
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL0

[back to top]

Terminal Elimination Half Life (t1/2) of MEDI3617

"The t1/2 is the time in days required for the concentration of the drug to reach half of its original value. Here, n is number of participants analyzed for this endpoint at a specific dose." (NCT01248949)
Timeframe: Days 1, 2 (MEDI3617 single agent only), 4, 8, 15 (Cycle 1); Day 1 (Cycle 2 and every cycle after), Day 15 (MEDI3617 + bev Q2W and MEDI3617 + paclitaxel only, Cycle 2 and every cycle after); end of treatment; 30 days and 3 months post last dose

,,,,
Interventionday (Mean)
Cohort -2 (n=1)Cohort 1 (n=1)Cohort 2 (n=2)Cohort 3 (n=3)Cohort 4 (n=2)Cohort 5 (n=2)Cohort OCE -1 (n=12)Cohort OCE 1 (n=2)Cohort MB 1A (n=3)Cohort MB 2A (n=3)Cohort MB 4A (n=2)Cohort MB 1B (n=7)Cohort MB 2B (n=3)Cohort MB 3B(n=2)Cohort MB 4B (n=1)Cohort MP1 (n=3)Cohort MP2 (n=1)Cohort MCP1 (n=1)Cohort MCP2 (n=2)
MEDI3617 + BEVACIZUMAB Q2W TOTALNANANANANANANANANANANA3.95.128.2310.2NANANANA
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNANANANANANANANA3.599.6712.3NANANANANANANANA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNANANANANANANANANANANANANANANANANA15.111.1
MEDI3617 + PACLITAXEL TOTALNANANANANANANANANANANANANANANA6.969.34NANA
MEDI3617 SINGLE AGENT TOTAL0.5851.265.865.987.687.7910.49.03NANANANANANANANANANANA

[back to top]

Maximum Tolerated Dose (MTD)

The dose-escalation phase used a 3 + 3 design. If greater than or equal to 2 (≥ 2) participants in a dose cohort experienced a DLT during the DLT period, the MTD was exceeded and no further participants were enrolled into that dose cohort. If this occurred, the preceding dose cohort was evaluated for the MTD and a total of 6 participants were treated at the preceding dose. If less than or equal to 1 (≤ 1) of 6 participants experienced a DLT at the preceding dose, then this dose level was the MTD. DLTs were defined as any treatment-related, grade 3 or higher toxicity (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.0); occurring during the first 21 or 28 days after the initial administration of MEDI3617. (NCT01248949)
Timeframe: From the time of first administration of MEDI3617 single agent or MEDI3617 combination therapy through the first 21-day or 28-day cycle (Cycle 1)

Interventionmilligram (mg) (Number)
MEDI3617 SINGLE AGENT TOTALNA
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTALNA
MEDI3617 + BEVACIZUMAB Q2W TOTALNA
MEDI3617 + PACLITAXEL TOTALNA
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTALNA

[back to top]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

An adverse event (AE) was any untoward medical occurrence in a participant administered investigational product and which does not necessarily have a causal relationship with this treatment. A serious adverse event (SAE) was an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events occurring after administration of investigational product. (NCT01248949)
Timeframe: From start of study drug administration up to 90 days after the last dose of MEDI3617

,,,,
InterventionParticipants (Number)
TEAEsTESAEs
MEDI3617 + BEVACIZUMAB Q2W TOTAL3818
MEDI3617 + BEVACIZUMAB Q3W ESCALATION TOTAL164
MEDI3617 + CARBOPLATIN/PACLITAXEL TOTAL74
MEDI3617 + PACLITAXEL TOTAL137
MEDI3617 SINGLE AGENT TOTAL4218

[back to top]

The Odds Ratio for the Relationship of Baseline Variables to the Carboplatin Hypersensitivity Rate

Perform exploratory analyses to correlate hypersensitivity rate to history of atopy, prior drug allergies, number of lifetime platinum cycles, duration since last platinum, and concomitant chemotherapy agent. (NCT01248962)
Timeframe: 2 years

InterventionOdds Ratio (Number)
# of Prior platinum-based regimens (>2 vs 1)Prior cisplatin regimenPlatinum-free intervalHistory of drug allergiesHistory of food allergiesHistory of atopy
Participants Who Experienced HSR2.51.510.82.22

[back to top]

Overall Response Rate

Tumor response was assessed every two cycles of completed therapy. Responses will be based on a comparison to the pretreatment tumor evaluation. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT01263782)
Timeframe: From treatment start to every two cycles of completed therapy.

,,,
InterventionParticipants (Count of Participants)
No change/Stable DiseasePartial RemissionProgressive Disease
Carboplatin + Pemetrexed + Bevacizumab Followed by Maintenance330
Carboplatin + Pemetrexed + Cetuximab Followed by Maintenance P210
Carboplatin + Pemetrexed + Cixutumumab Followed by Maintenance320
Carboplatin + Pemetrexed x 4 Cycles Followed by Maintenance Pe501

[back to top]

Progression Free Survival

It is defined as from treatment start to the time of progression or death, whichever occurred first, or to the time of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01263782)
Timeframe: From treatment start to the time of progression or death, whichever occurred first, or to the time of last contact, assessed up to 5 years

Interventionmonth (Median)
Carboplatin + Pemetrexed x 4 Cycles Followed by Maintenance Pe5.2
Carboplatin + Pemetrexed + Bevacizumab Followed by Maintenance14.5
Carboplatin + Pemetrexed + Cetuximab Followed by Maintenance P20.6
Carboplatin + Pemetrexed + Cixutumumab Followed by Maintenance8

[back to top]

Area Under the Concentration-Time Curve Over the Dosing Interval (AUCtau) of MEDI-575 After First Dose

The AUCtau defined as area under the plasma concentration time profile from time zero to the end of the dosing interval (tau). The AUCtau of MEDI-575 after first dose is reported. (NCT01268059)
Timeframe: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15

Interventionmicrogram*day per milliliter (Mean)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b3550
Carboplatin/Paclitaxel + MEDI-575 - Phase 24803

[back to top]

Trough Serum Concentration at Steady State (Ctrough,ss) of MEDI-575

The Ctrough,ss of MEDI-575 is reported. (NCT01268059)
Timeframe: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)

Interventionmicrogram per milliliter (Mean)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b375
Carboplatin/Paclitaxel + MEDI-575 - Phase 2168

[back to top]

Time to Progression (TTP)

The TTP was measured from randomization until the documentation of disease progression. Disease progression defined according to RECIST version 1.1 guidelines. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The TTP was evaluated using Kaplan-Meier method. (NCT01268059)
Timeframe: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)

Interventionmonths (Median)
Carboplatin/Paclitaxel - North America/European Union (EU)6.4
Carboplatin/Paclitaxel + MEDI-575 - North America/EU4.6
Carboplatin/Paclitaxel - Japan6.5
Carboplatin/Paclitaxel + MEDI-575 - Japan4.6

[back to top]

Time to Maximum Serum Concentration at Steady State (Tmax,ss) of MEDI-575

The Tmax,ss of MEDI-575 is reported. (NCT01268059)
Timeframe: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)

Interventionday (Mean)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b0.042
Carboplatin/Paclitaxel + MEDI-575 - Phase 20.049

[back to top]

Time of Maximal Observed Concentration (Tmax) of MEDI-575 After First Dose

The tmax refers to the time after dosing when a drug attains its highest measurable concentration (Cmax). The Tmax of MEDI-575 after first dose is reported. (NCT01268059)
Timeframe: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15

Interventionday (Mean)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b0.044
Carboplatin/Paclitaxel + MEDI-575 - Phase 20.046

[back to top]

Percentage of Participants With Positive Anti-MEDI-575 Antibodies

Immunogenicity assessment included determination of anti-drug (MEDI-575) antibodies in serum samples. (NCT01268059)
Timeframe: Day 1 (prior to infusion) of Cycles 1 to 7 (21-day cycle), end of treatment, 30 and 60 days after the last dose (approximately 3 years)

Interventionpercentage of participants (Number)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b25.0
Carboplatin/Paclitaxel + MEDI-575 - Phase 226.5

[back to top]

Progression Free-Survival (PFS)

Progression-free survival defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (defined according to Response Evaluation Criteria for Solid Tumors [RECIST] version 1.1 guidelines) or death due to any cause, whichever occurs first. Participants without progression or death at the time of analysis were censored at their last date of tumor evaluation. PFS was assessed only in North America/European Union (EU) participants. Progression-free survival was evaluated using Kaplan-Meier method. (NCT01268059)
Timeframe: From randomization until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)

Interventionmonths (Median)
Carboplatin/Paclitaxel - North America/European Union (EU)5.5
Carboplatin/Paclitaxel + MEDI-575 - North America/EU4.6

[back to top]

Overall Survival (OS)

Overall survival defined as the time from initiation of study treatment until death due to any cause. Participants who were still alive at the time of analysis were censored at their last date of last contact. The OS was evaluated using Kaplan-Meier method. (NCT01268059)
Timeframe: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)

Interventionmonths (Median)
Carboplatin/Paclitaxel - North America/European Union (EU)11.8
Carboplatin/Paclitaxel + MEDI-575 - North America/EU10.0
Carboplatin/Paclitaxel - JapanNA
Carboplatin/Paclitaxel + MEDI-575 - Japan11.5

[back to top]

Objective Response Rate (ORR)

The ORR defined as the percentage of participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment greater than or equal to (>=) 4 weeks after the initial documentation of response. The ORR was evaluated using Kaplan-Meier method. (NCT01268059)
Timeframe: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)

Interventionpercentage of participants (Number)
Carboplatin/Paclitaxel - North America/European Union (EU)22.5
Carboplatin/Paclitaxel + MEDI-575 - North America/EU31.7
Carboplatin/Paclitaxel - Japan33.3
Carboplatin/Paclitaxel + MEDI-575 - Japan12.5

[back to top]

Number of Participants With Dose Limiting Toxicities (DLT): Phase 1b

"A DLT was defined as:~Any treatment-related Grade 3 or higher non-hematologic toxicity that occurred during the DLT assessment period with the following exceptions:~Grade 3 fever (in the absence of neutropenia) defined as more than (>) 40.0 degree Celcius (> 104.0 degree Fahrenheit) that resolved to normal or baseline within 24 hours of treatment and was not considered a serious adverse event (SAE); or~Grade 3 rigors/chills that responded to optimal therapy.~Any treatment-related Grade 3 or higher hematologic toxicity." (NCT01268059)
Timeframe: From Day 1 to Day 21 of first cycle

InterventionParticipants (Count of Participants)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b0

[back to top]

Maximum Serum Concentration at Steady State (Cmax,ss) of MEDI-575

The Cmax,ss of MEDI-575 is reported. (NCT01268059)
Timeframe: Cycle 1 (pre-infusion and end of infusion on Day 1, Day 2, Day 8, and Day 15); Day 1 of Cycles 2 to 4 (pre-infusion and end of infusion)

Interventionmicrogram per milliliter (Mean)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b2997
Carboplatin/Paclitaxel + MEDI-575 - Phase 2619.7

[back to top]

Time to Response (TTR)

The TTR was measured from initiation of study treatment to the first documentation of objective response (OR). The OR defined as the participants with confirmed CR or confirmed PR according to RECIST version 1.1 guidelines. Confirmed responses were those that persist on repeat imaging or assessment >=4 weeks after the initial documentation of response. The TTR was evaluated using Kaplan-Meier method. (NCT01268059)
Timeframe: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)

Interventionmonths (Median)
Carboplatin/Paclitaxel - North America/European Union (EU)1.4
Carboplatin/Paclitaxel + MEDI-575 - North America/EU1.4
Carboplatin/Paclitaxel - Japan2.2
Carboplatin/Paclitaxel + MEDI-575 - Japan2.8

[back to top]

Duration of Response (DR)

The DR defined as the duration from the first documentation of OR to the first documented disease progression. Participants without progression at the time of analysis were censored at their last date of tumor evaluation. The DR was evaluated using Kaplan-Meier method. (NCT01268059)
Timeframe: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)

Interventionmonths (Median)
Carboplatin/Paclitaxel - North America/European Union (EU)3.3
Carboplatin/Paclitaxel + MEDI-575 - North America/EU4.2
Carboplatin/Paclitaxel - Japan4.9
Carboplatin/Paclitaxel + MEDI-575 - Japan2.1

[back to top]

Best Overall Response

Best overall response of a participant was defined as the best tumor response [Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD)] observed during the trial period assessed according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1 criteria. The participant's best overall response assignment depended on the findings of both target and non-target disease and also on the appearance of new lesions. CR was defined as disappearance of tumor lesions, PR was defined as a decrease of at least 30 percent (%) in the sum of diameters of target lesion, SD was defined as steady state of disease, and PD was defined as an increase of at least 20% in the sum of diameters of target lesions. (NCT01268059)
Timeframe: From initiation of treatment until the end of study (14 months from last participant enrolled or sponsor stopped the study), assessed at every 6 weeks until disease progression and every 3 months until the end of the study (approximately 3 years)

,,,
InterventionParticipants (Count of Participants)
Complete responsePartial responseStable diseaseProgressive diseaseUnknown
Carboplatin/Paclitaxel - Japan02310
Carboplatin/Paclitaxel - North America/European Union (EU)1121917
Carboplatin/Paclitaxel + MEDI-575 - Japan01511
Carboplatin/Paclitaxel + MEDI-575 - North America/EU0191255

[back to top]

Number of Participants With Abnormalities in Laboratory Investigations Reported as AEs or SAEs

Laboratory investigations included hematology, coagulation, serum chemistry and urinalysis parameters. Participants with abnormalities in these laboratory investigations recorded as AEs or SAEs were reported. (NCT01268059)
Timeframe: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)

,
InterventionParticipants (Count of Participants)
AnaemiaFebrile neutropeniaIdiopathic thrombocytopenic purpuraLeukopeniaLymphadenopathyLymphopeniaNeutropeniaThrombocytopeniaActivated partial thromboplastin time prolongedHaemoglobin decreasedLymphocyte count decreasedNeutrophil count decreasedPlatelet count decreasedWhite blood cell count decreasedAlanine aminotransferase increasedAspartate aminotransferase increasedBlood alkaline phosphatase increasedBlood bilirubin increasedBlood creatinine increasedBlood magnesium decreasedGamma-glutamyl transferase increasedElectrolyte imbalanceHypercholesterolaemiaHyperglycaemiaHypertriglyceridaemiaHypoalbuminaemiaHypocalcaemiaHypoglycaemiaHypokalemiaHypomagnesaemiaHyponatraemiaHypophosphataemiaIron deficiencyVitamin B12 deficiencyUrine analysis abnormalSpecific gravity urine increasedHaematuriaProteinuriaPyelocaliectasis
Carboplatin/Paclitaxel (Total)15302027301055423221001152331810420000110
Carboplatin/Paclitaxel + MEDI-575 (Total)2561621131015114910542031100717611220841111111

[back to top]

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. (NCT01268059)
Timeframe: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)

,
InterventionParticipants (Count of Participants)
Any AEAny SAE
Carboplatin/Paclitaxel (Total)4217
Carboplatin/Paclitaxel + MEDI-575 (Total)5325

[back to top]

Maximum Observed Serum Concentration (Cmax) of MEDI-575 After First Dose

The Cmax of MEDI-575 after first dose is reported. (NCT01268059)
Timeframe: Day 1 (pre-infusion and end of infusion), Day 2 (24 hours post Day 1 infusion), Day 8, and Day 15

Interventionmicrogram per milliliter (Mean)
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b589.3
Carboplatin/Paclitaxel + MEDI-575 - Phase 2628.9

[back to top]

Number of Participants With PDGFRα Expression in Stromal Cells of Archived Tumor Samples

The immunohistochemical expression of PDGFRα in stromal cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining stromal cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent). (NCT01268059)
Timeframe: Baseline (Screening [Days -28 to -1])

,,
InterventionParticipants (Count of Participants)
Intensity: 1+Intensity: 2+Intensity: 3+Localization: cytoplasmicLocalization: membranousLocalization: nuclearFrequency: rareFrequency: occasionalFrequency: frequent
Carboplatin/Paclitaxel - Phase 23521000136
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b210300012
Carboplatin/Paclitaxel + MEDI-575 - Phase 231031510349

[back to top]

Number of Participants With Platelet-derived Growth Factor Receptor Alpha (PDGFRα) Expression in Tumor Cells of Archived Tumor Samples

The immunohistochemical expression of PDGFRα in tumor cells in archived formalin-fixed paraffin-embedded tissue samples collected at baseline are reported. The transmembrane receptor tyrosine kinase PDGFRα plays an important role in human carcinogenesis, both as a direct target on tumor cells and also as a mediator of stromal support for cancer cell growth. The data of positive-staining tumor cells are reported in 3 categories: intensity (1+ [weak expression, staining in <5 % of tumor cells]; 2+ [moderate expression, staining in >= 5 % of tumor cells]; and 3+ [strong expression, staining in >5 % of the tumor cells]), localization (membranous, cytoplasmic, or nuclear), and frequency (rare, occasional, or frequent). (NCT01268059)
Timeframe: Baseline (Screening [Days -28 to -1])

,,
InterventionParticipants (Count of Participants)
Intensity: 1+Intensity: 2+Intensity: 3+Localization: cytoplasmicLocalization: membranousLocalization: nuclearFrequency: rareFrequency: occasionalFrequency: frequent
Carboplatin/Paclitaxel - Phase 2300201111
Carboplatin/Paclitaxel + MEDI-575 - Phase 1b100001100
Carboplatin/Paclitaxel + MEDI-575 - Phase 2221320302

[back to top]

Number of Participants With Electrocardiogram (ECG) Abnormalities Reported as AEs

The 12-lead ECG data were performed and obtained in triplicate that is 3 ECGs obtained within a 5 minute time period. Number of participants with ECG abnormalities were reported and recorded as AEs. (NCT01268059)
Timeframe: From signing of informed consent form until 90 days post the last dose treatment (approximately 3 years)

,
InterventionParticipants (Count of Participants)
Atrial fibrillationAtrial flutterAtrioventricular block first degreeMyocardial infarctionTachycardia
Carboplatin/Paclitaxel (Total)00012
Carboplatin/Paclitaxel + MEDI-575 (Total)11103

[back to top]

Number of Participants With Complete Control Defined as no Vomiting and no Use of Rescue Medications (for Nausea or Emesis)

Number of participants who had complete control defined by no vomiting (NCT01275664)
Timeframe: During the 6 days following chemotherapy

InterventionParticipants (Count of Participants)
Treatment (Granisetron, Dexamethasone, Aprepitant)1

[back to top]

Frequency of Adverse Effects as Assessed by the NCI CTCAE v 4.0

Adverse events at least possibly related to treatment (NCT01275664)
Timeframe: Up to day 6

InterventionParticipants (Count of Participants)
ConstipationFatigueDiarrheaHyponatremiaAlanine Aminotransferase IncreasedGGT Increased
Treatment (Granisetron, Dexamethasone, Aprepitant)111111

[back to top]

Overall Survival

Evaluated and compared between the two treatment groups using log-rank statistics and graphically using the methods of Kaplan and Meier. (NCT01280058)
Timeframe: From study entry to the time of death due to any cause, assessed up to 4 years

Interventionmonths (Median)
Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)7.3
Arm B (Carboplatin, Paclitaxel)8.8

[back to top]

Overall Response Rate (Partial or Complete Response) Evaluated Using the Standard RECIST v. 1.1

95% confidence intervals will be calculated. Differences in objective response rates between the treatment arms will be assessed using Fisher's exact test. (NCT01280058)
Timeframe: Up to 4 years

,
InterventionParticipants (Count of Participants)
Partial ResponseComplete Response
Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)70
Arm B (Carboplatin, Paclitaxel)70

[back to top]

Progression-free Survival Using RECIST v. 1.1

The progression-free survival distributions between the two arms will be compared using log-rank tests. Progression-free survival curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. (NCT01280058)
Timeframe: From study entry to the date of documented progression and/or death, assessed up to 4 years

Interventionmonths (Median)
Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)4.9
Arm B (Carboplatin, Paclitaxel)5.2

[back to top]

Percentage of Patients With Ras Pathway Activation

The 95% confidence interval will be assessed. Cochran-Mantel-Haenszel test will be used to assess differences in the relationships between response and Ras pathway activation and the association of treatment groups on these relationships. (NCT01280058)
Timeframe: Baseline

Interventionpercentage of patients (Number)
Arm A (Wild-type Reovirus, Carboplatin, Paclitaxel)71
Arm B (Carboplatin, Paclitaxel)75

[back to top] [back to top]

To Measure the Safety and Clinical Effectiveness of the Combination of Carboplatin, Cetuximab and RAD001 in Patients With Advanced (Recurrent or Metastatic) Head and Neck Cancer

This phase 1 clinical trial used a standard 3 + 3 design. Four dose levels of everolimus were planned to be evaluated, and the standard 3 + 3 design with dose de-escalation was used in the trial. Namely, 3 patients were assigned to starting dose level 1. If no dose-limiting toxicity (DLT) was observed, the trial proceeded to the next dose level, and another cohort of 3 patients was enrolled. If at least 2 of the 3 patients experienced at least 1 DLT, then the dose level decreased; otherwise, if only 1 patient experienced DLT, then 3 more patients were enrolled at the same dose level. If none of the 3 additional patients experienced DLT, the dose was escalated; otherwise, the dose level decreased. Dose reduction continued until a dose level was reached at which 6 patients had been treated and at most 1 DLT was observed. (NCT01283334)
Timeframe: Within the first 21 days of therapy

Interventionparticipants (Number)
Everolimus Dose Level 1 DLT2
Everolimus Dose Level -1 DLT1

[back to top]

Progression-free Survival (PFS)

Objective tumor responses were assessed every 2 cycles of chemotherapy with computed tomography or positron emission tomography/ computed tomography scans in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) criteria. (NCT01283334)
Timeframe: The time of PFS was calculated as the time from study enrollment to the disease progression date, death date, or last contact, whichever came first, up to 25 months

Interventionmonths (Median)
Carboplatin, Cetuximab and Everolimus8.15

[back to top]

Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy at Primary Endpoint

Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Analysis for the Primary Endpoint occurred when the following 2 conditions were both met: (1) 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and (2) 705 deaths were observed in all randomized participants. (NCT01285609)
Timeframe: Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start)

Interventionmonths (Median)
Ipilimumab With Paclitaxel/Carboplatin13.37
Placebo With Paclitaxel/Carboplatin12.42

[back to top]

Median Number of Months With Progression Free Survival (PFS) Per mWHO in Participants Who Have Received at Least One Dose of Blinded Study Therapy at Primary Endpoint

Progression-free survival (PFS) is defined as the time between the date of randomization and the date of tumor progression per Modified World Health Organization (mWHO) criteria or death, whichever occurs first. A participant who died without reported progression per mWHO criteria were considered to have progressed on the date of death. For participants who remain alive and have not progressed, PFS was censored on the date of last evaluable tumor assessment. For participants who remain alive and have no recorded post-baseline tumor assessment, PFS was censored on the day of randomization. (NCT01285609)
Timeframe: Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start)

Interventionmonths (Median)
Ipilimumab With Paclitaxel/Carboplatin5.55
Placebo With Paclitaxel/Carboplatin5.59

[back to top]

Overall Survival (OS) in All Randomized Participants at Primary Endpoint

Overall Survival (OS) was defined as the time from randomization to the date of death. Participants that had not died were censored at last known date alive. Median OS time was calculated using Kaplan-Meier Estimates. Analysis for the Primary Endpoint occurred when the following 2 conditions were both met: (1) 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and (2) 705 deaths were observed in all randomized participants. (NCT01285609)
Timeframe: Randomization until 518 deaths were observed in randomized participants treated with at least one dose of blinded study therapy and 705 deaths were observed in all randomized participants, up to June 2015 (approximately 48 months post study start)

Interventionmonths (Median)
Ipilimumab With Paclitaxel/Carboplatin10.94
Placebo With Paclitaxel/Carboplatin10.74

[back to top]

Number of Participants With Best Overall Tumor Response

Best overall observed tumor response at any point during the study until disease progression/recurrence defined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Complete Response (CR) was defined as the disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm) and normalization of tumor marker level of non-target lesions; Partial Response (PR) was defined as at least 30% decrease in sum of longest diameter of target lesions; Progressive Disease (PD) was defined as at least 20% increase in sum of longest diameter of target lesions and minimum 5 mm increase over nadir; Stable Disease (SD) was defined as small changes that did not meet above criteria. (NCT01287520)
Timeframe: Baseline up to Cycle 9 (Cycle 1 was 28 days, Cycles 2 to 9 were 21 days)

,,,,,,,,
Interventionparticipants (Number)
CRPRSDPDUnknown (discontinued before response assessment)
LY 10/Carb 5/Pem 500 (Cohort 1)00201
LY 10/Carb 6/Pem 500 (Cohort 2)00421
LY 120/Carb 6/Pem 500 (Cohort 6)00000
LY 20/Carb 6/Pem 500 (Cohort 3)01211
LY 40/Carb 6/Pem 500 (Cohort 4)01230
LY 40/Carb 6/Pem 500 + R50 (Cohort 9)00221
LY 60/Carb 6/Pem 500 + R50 (Cohort 8)01120
LY 80/Carb 6/Pem 500 (Cohort 5)00012
LY 80/Carb 6/Pem 500 + R50 (Cohort 7)01100

[back to top] [back to top]

PK Parameter: Maximum Plasma Concentration (Cmax) of Pemetrexed (Pem)

Cmax of Pem given as a single dose with Carb (doublet therapy) and when coadministered with Carb and LY2090314 (triplet therapy). (NCT01287520)
Timeframe: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle

Interventionnanogram per milliliter per milligram (Geometric Mean)
Pemetrexed (Doublet Therapy)109
Pemetrexed (Triplet Therapy)108

[back to top]

PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)

(NCT01287520)
Timeframe: Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle

Interventionnanograms per milliliter (Geometric Mean)
LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)106
LY 20/Carb 6/Pem 500 (Cohort 3)271
LY 40/Carb 6/Pem 500 (Cohorts 4 and 9)657
LY 80/Carb 6/Pem 500 (Cohorts 5 and 7)1150
LY 120/Carb 6/Pem 500 (Cohort 6)768
LY 60/Carb 6/Pem 500 + R50 (Cohort 8)1040

[back to top]

PK Parameter: Maximum Plasma Concentration (Cmax) of LY2090314

(NCT01287520)
Timeframe: Cycle 1 Day 1 of a 28-day cycle

Interventionnanograms per milliliter (Geometric Mean)
LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)122
LY 20/Carb 6/Pem 500 (Cohort 3)246
LY 40/Carb 6/Pem 500 (Cohorts 4 and 9 )603
LY 80/Carb 6/Pem 500 (Cohorts 5 and 7898
LY 120/Carb 6/Pem 500 (Cohort 6)1700
LY 60/Carb 6/Pem 500 + R50 (Cohort 8)881

[back to top]

PK Parameter: Cmax of Free Carboplatin

Cmax of free Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy). (NCT01287520)
Timeframe: Cycle 1, Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle

Interventionnanograms/milliliter/milligram (Geometric Mean)
Carboplatin (Doublet Therapy)24.0
Carboplatin (Triplet Therapy)25.5

[back to top]

PK Parameter: AUC0-∞ of Free Carboplatin (Carb)

AUC0-∞ of free Carb was calculated from the area under the concentration versus time curves of Carb given as a single dose with Pem (doublet therapy) and when co-administered with Pem and LY2090314 (triplet therapy). (NCT01287520)
Timeframe: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 9: Day 1 of 21-day cycle

Interventionhours*nanograms per milliliter per mg (Geometric Mean)
Carboplatin (Doublet Therapy)81.6
Carboplatin (Triplet Therapy)88.1

[back to top]

PK Parameter: AUC0-∞ of LY2090314 Coadministered With Pemetrexed (Pem) and Carboplatin (Carb)

AUC0-∞ was calculated from the area under the concentration versus time curves of LY2090314 from time zero to infinity when coadministered with Pem and Carb. (NCT01287520)
Timeframe: Cycle 1 Day 8 of a 28-day cycle or Cycle 2 Day 1 of a 21-day cycle

Interventionnanograms*hour per milliliter (Geometric Mean)
LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)192
LY 20/Carb 6/Pem 500 (Cohort 3)404
LY 40/Carb 6/Pem 500 (Cohorts 4 and 9)938
LY 80/Carb 6/Pem 500 (Cohorts 5 and 7)1830
LY 120/Carb 6/Pem 500 (Cohort 6)2190
LY 60/Carb 6/Pem 500 + R50 (Cohort 8)1570

[back to top]

Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of Pemetrexed (Pem)

AUC0-∞ was calculated from the area under the concentration versus time curves of Pem given as a single dose with Carb (doublet therapy) and when co-administered with Carb and LY2090314 (triplet therapy). (NCT01287520)
Timeframe: Cycle 1 Day 8 of 28-day cycle and Cycle 2 up to Cycle 10 Day 1 of 21-day cycle

Interventionhours*nanograms/milliliter/ milligram (Geometric Mean)
Pemetrexed (Doublet Therapy)212
Pemetrexed (Triplet Therapy)202

[back to top]

Pharmacokinetic (PK) Parameter: Area Under the Concentration-Time Curve From Time 0 Hour to Infinity (AUC0-∞) of LY2090314

AUC0-∞ was calculated from the area under the concentration versus time curve from time 0 to infinity of LY2090314 when administered alone. (NCT01287520)
Timeframe: Cycle 1 Day 1 of a 28 day cycle

Interventionnanograms*hour per milliliter (Geometric Mean)
LY 10/Carb 5 or Carb 6/Pem 500 (Cohorts 1 and 2)216
LY 20/Carb 6/Pem 500 (Cohort 3)427
LY 40/Carb 6/Pem 500 (Cohorts 4 and 9)976
LY 80/Carb 6/Pem 500 (Cohorts 5 and 7)1870
LY 120/Carb 6/Pem 500 (Cohort 6)3310
LY 60/Carb 6/Pem 500 + R50 (Cohort 8)1600

[back to top]

Number of Patients Who Experience Grade 2 or Higher Late Toxicities at or More Than 6 Months After Completion of Radiation Treatment (RT)

(NCT01289353)
Timeframe: 6 months to 5 years post-RT

InterventionParticipants (Count of Participants)
ChemoRT18

[back to top]

Number of Patients Who Experience Acute Toxicities at or More Than 6 Months After Completion of Radiation Treatment (RT)

Acute Toxicities include all Grade 1 toxicities (NCT01289353)
Timeframe: 6 months to 5 year post-RT

InterventionParticipants (Count of Participants)
ChemoRT67

[back to top]

Number of Patients Who Developed Grade 2-3 Acute Radiation Dermatitis Within 60 Days Post-RT

(NCT01289353)
Timeframe: 60 days post-RT

InterventionParticipants (Count of Participants)
ChemoRT8

[back to top]

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01295944)
Timeframe: Date treatment consent signed to date off study, approximately, 112 months and 28 days.

InterventionParticipants (Count of Participants)
1/Carboplatin and Bevacizumab for Recurrent Ependymoma22

[back to top]

Overall Survival (OS)

OS was calculated by the Kaplan Meier methodology. OS is defined as the time from treatment start date until date of death or date last known alive. (NCT01295944)
Timeframe: The time from treatment start date until date of death or date last known alive, up to 68 months

InterventionMonths (Median)
1/Carboplatin and Bevacizumab for Recurrent Ependymoma18.0

[back to top]

Percentage of Participants That Have Progressive Free Survival (PFS) After 1 Year

Percentage of participants that have progressive disease after 1 year. Kaplan-Meier method is used for the analyses of PFS. Progression is a 25% increase in the sum of products of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline. Clear worsening of any evaluable disease, or appearance of any new lesion/site, clear clinical worsening or failure to return for evaluation due to death or deteriorating condition (unless clearly unrelated to this cancer). (NCT01295944)
Timeframe: 1 year

InterventionPercentage of participants (Number)
1/Carboplatin and Bevacizumab for Recurrent Ependymoma76.4

[back to top]

Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Spine Tumors (MDASI-SP) Instrument

The MDASI-SP consists of 23 symptoms rated on an 11 point scale (0 - not present, to 10 - as bad as you can imagine) to indicate the presence and severity of the symptom. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom severity score rated on the scale from 0-not present to 10-as bad as you can imagine at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening. (NCT01295944)
Timeframe: Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days)

Interventionscore on a scale (Mean)
BaselineCycle 2Cycle 4Cycle 6
1/Carboplatin and Bevacizumab for Recurrent Ependymoma1.42.12.11.5

[back to top]

Mean Symptom Interference With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT)

The MDASI-BT consists of 23 symptoms rated on an 11 point scale (0 - did not interfere, to 10 - interfered completely) to indicate the symptoms that interfere with a participants life in the last 24 hours. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom interference score rated on the scale from 0- did not interfere, to 10- interfered completely at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom interference measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening. (NCT01295944)
Timeframe: Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days)

Interventionscore on a scale (Mean)
BaselineCycle 2Cycle 4Cycle 6
1/Carboplatin and Bevacizumab for Recurrent Ependymoma1.62.11.72.5

[back to top]

Mean Symptom Interference With Daily Activities Using the MD Anderson Symptom Inventory for Spine Tumors (MDASI-SP) Instrument

The MDASI-SP consists of 23 symptoms rated on an 11 point scale (0 - did not interfere, to 10 - interfered completely) to indicate the symptoms that interfere with a participants life in the last 24 hours. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom interference score rated on the scale from 0- did not interfere, to 10- interfered completely at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom interference measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening. (NCT01295944)
Timeframe: Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days)

Interventionscore on a scale (Mean)
BaselineCycle 2Cycle 4Cycle 6
1/Carboplatin and Bevacizumab for Recurrent Ependymoma1.73.14.14.2

[back to top]

Number of Participants With a (Complete Response (CR) + Partial Response (PR))

Response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR) is complete disappearance of all measurable and evaluable disease. No new lesions. Partial Response (PR) is greater than or equal to 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. (NCT01295944)
Timeframe: Up to 6 months and 1 week

InterventionParticipants (Count of Participants)
Complete ResponsePartial Response
1/Carboplatin and Bevacizumab for Recurrent Ependymoma02

[back to top]

Mean Core Symptom Severity With Daily Activities Using the MD Anderson Symptom Inventory for Brain Tumors (MDASI-BT)

The MDASI-BT consists of 23 symptoms rated on an 11 point scale (0 - not present, to 10 - as bad as you can imagine) to indicate the presence and severity of the symptom. All participants with at least one valid questionnaire are included in the analyses. We calculated the mean core symptom severity score rated on the scale from 0-not present to 10-as bad as you can imagine at the time of clinical evaluation. Differences of at least 2 points will be classified as the minimum clinically meaningful change in the symptom severity measures. For example, an increase of 2 points or more would mean a moderate improvement, whereas a decrease of 2 points or more would be interpreted as moderate worsening. (NCT01295944)
Timeframe: Completed at baseline, before a brain or spine magnetic resonance imaging (MRI)/clinical evaluation, and at cycle 2, cycle 4, and cycle 6 (each cycle is 28 days)

Interventionscore on a scale (Mean)
BaselineCycle 2Cycle 4Cycle 6
1/Carboplatin and Bevacizumab for Recurrent Ependymoma1.52.11.31.9

[back to top]

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Nintedanib

Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of nintedanib during course 1 and course 2 (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration

,
Interventionnanogram*hour/millilitre (ng*h/mL) (Geometric Mean)
Treatment Course 1 (150mg: N=5; 200mg: N=10)Treatment Course 2 (150mg: N=7)
Nintedanib 150mg335482
Nintedanib 200mg482NA

[back to top]

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carboplatin (Determined as Total Platinum)

Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC0-inf) of carboplatin (determined as total platinum) during treatment course 1 and course 2. (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 26h, 28h, 32h, 48h, 168h, 336h and 480h after drug administration

,
Interventionng/mL (Geometric Mean)
Treatment Course 1 (200mg:N=10; All Patients:N=16)Treatment Course 2 (200mg:N=7; All Patients:N=16)
All Patients267000324000
Nintedanib 200mg271000325000

[back to top]

Maximum Tolerated Dose of Nintedanib Based on the Occurrence of DLTs During Treatment Course 1

Maximum Tolerated Dose (MTD) of nintedanib in combination with carboplatin and pegylated liposomal doxorubicin based on the occurrence of dose limiting toxicities (DLTs) during treatment course 1. MTD will be determined among the first 6 evaluable patients in each dose level. MTD is the highest dose at which the incidence of DLT is less than 2/6. (NCT01314105)
Timeframe: First 28-day treatment cycle

Interventionmg (Number)
Nintedanib 150mgNA
Nintedanib 200mg200

[back to top]

Dose Limiting Toxicities During Treatment Course 1

"Number of patients with dose limiting toxicity (DLT) occurring during treatment course 1~The following AEs were to be reported as DLT events if their occurrence was considered to be drug-related:~Haematological toxicity:~Any CTCAE grade 4 haematological toxicity~CTCAE grade 4 neutropenia that was not associated with fever ≥38.5°C, if persisting for >7 days despite adequate supportive treatment~CTCAE grade ≥3 neutropenia of any duration if associated with fever ≥38.5°C~Any CTCAE grade 4 thrombocytopenia~CTCAE grade ≥3 thrombocytopenia if associated with bleeding of CTCAE grade ≥2~Non-haematological toxicity:~CTCAE grade ≥3 diarrhoea despite optimal medical management~CTCAE grade 2 diarrhoea persisting for more than 7 days despite optimal medical management~CTCAE grade ≥2 vomiting despite optimal medical management~ALT and/or AST elevation of CTCAE grade ≥3~ALT and/or AST elevation of >3x ULN in conjunction with bilirubin increase >2x ULN" (NCT01314105)
Timeframe: First 28-day treatment cycle

Interventionparticipants (Number)
Nintedanib 150mg1
Nintedanib 200mg1

[back to top]

Maximum Measured Plasma Concentration (Cmax) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2

"The maximum measured plasma concentration (Cmax) of pegylated liposomal doxorubicin (PLD) (determined as total plasma doxorubicin) during treatment course 1 and course 2.~Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 1 as for only 2 patients evaluable concentrations were available." (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 25h, 27h, 30h, 34h, 48h, 168h, 336h and 480h after drug administration

,
Interventionµg/mL (Geometric Mean)
Treatment Course 1 (200mg:N=NA; All Patients:N=8)Treatment Course 2 (200mg:N=3; All Patients:N=8)
All Patients18.919.0
Nintedanib 200mgNA19.0

[back to top]

Maximum Measured Plasma Concentration (Cmax) of Nintedanib

Maximum measured plasma concentration (Cmax) of nintedanib during course 1 and course 2 (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration

,
Interventionng/mL (Geometric Mean)
Treatment Course 1 (150mg: N=6; 200mg: N=11)Treatment Course 2 (150mg: N=8; 200mg: N=7)
Nintedanib 150mg38.865.8
Nintedanib 200mg69.082.2

[back to top]

Maximum Measured Plasma Concentration (Cmax) of Carboplatin During Course 1 and Course 2 (Determined as Ultrafilterable Platinum)

Maximum measured plasma concentration (Cmax) of carboplatin during course 1 and course 2 (determined as ultrafilterable platinum). (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 25h, 26h, 27h, 28h, 30h, 32h, and 34h after drug administration

,
Interventionng/mL (Geometric Mean)
Treatment Course 1 (200mg:N=9; All Patients:N=16)Treatment Course 2 (200mg:N=6; All Patients:N=15)
All Patients2460024400
Nintedanib 200mg2600027000

[back to top]

Maximum Measured Plasma Concentration (Cmax) of Carboplatin (Total Platinum)

Maximum measured plasma concentration (Cmax) of carboplatin during course 1 and course 2 (determined as total platinum). (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 26h, 28h, 32h, 48h, 168h, 336h and 480h after drug administration

,
Interventionng/mL (Geometric Mean)
Treatment Course 1 (200mg:N=10; All Patients:N=16)Treatment Course 2 (200mg:N=7; All Patients:N=16)
All Patients2400023900
Nintedanib 200mg2460027100

[back to top]

Incidence and Intensity of Adverse Events

"Safety of nintedanib as indicated by intensity and incidence of adverse events, graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0.~The CTCAE grades are the worst grade per patient. The CTCAE grades are Grade 1 as mild AE, Grade 2 as moderate AE, Grade 3 as severe AE, Grade 4 as lifethreatening or disabling AE, and Grade 5 as death related to AE." (NCT01314105)
Timeframe: From the first drug administration until 28 days after the last drug administration, up to 31 months

,
Interventionparticipants (Number)
Grade 1Grade 2Grade 3Grade 4Grade 5
Nintedanib 150mg02320
Nintedanib 200mg00930

[back to top]

Change From Baseline in Safety Laboratory Parameters

Change from baseline in safety laboratory parameters. (NCT01314105)
Timeframe: From the first drug administration until 28 days after the last drug administration, up to 31 months

,
Interventionpercentage of participants (Number)
Alanine aminotransferase increasedAspartate aminotransferase increasedGamma-glutamyltransferase increasedPlatelet count decreasedBlood alkaline phosphataseBlood lactate dehydrogenase increasedBlood alkaline phosphatase increasedHaemoglobin decreasedNeutrophil count decreasedBlood bilirubin increasedBlood creatinine decreasedGamma-glutamyltransferaseHaemoglobinNeutrophil countWhite blood cell count decreasedAmylase increasedBlood creatinine increasedPlatelet count increased
Nintedanib 150mg57.171.442.928.628.628.614.30014.314.314.314.314.314.3000
Nintedanib 200mg91.791.766.758.3016.725.016.716.78.3000008.38.38.3

[back to top]

Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC 0-inf) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2

"Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) of pegylated liposomal doxorubicin (PLD) (determined as total plasma doxorubicin) during treatment course 1 and course 2.~Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 1 as for only 2 patients evaluable concentrations were available." (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 25h, 27h, 30h, 34h, 48h, 168h, 336h and 480h after drug administration

,
Interventionµg*h/mL (Geometric Mean)
Treatment Course 1 (200mg:N=NA; All Patients:N=8)Treatment Course 2 (200mg:N=3; All Patients:N=10)
All Patients22802300
Nintedanib 200mgNA2120

[back to top]

Area Under the Plasma Concentration-time Curve Over the Time Interval From Zero Extrapolated to Infinity (AUC 0-inf) of Carboplatin During Treatment Course 1 and Course 2 (Determined as Ultrafilterable Platinum)

"Area under the plasma concentration-time curve over the time interval from zero extrapolated to infinity (AUC 0-inf) of carboplatin during treatment course 1 and course 2 (determined as ultrafilterable platinum).~Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 2 as 2/3 of patients had quantifiable values." (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 25h, 26h, 27h, 28h, 30h, 32h, and 34h after drug administration

,
Interventionng*h/mL (Geometric Mean)
Treatment Course 1 (200mg:N=9; All Patients:N=16)Treatment Course 2 (200mg:N=NA; All Patients:N=NA)
All Patients70700NA
Nintedanib 200mg71000NA

[back to top]

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of PLD (Determined as Total Plasma Doxorubicin) During Treatment Course 1 and Course 2

"Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of pegylated liposomal doxorubicin (PLD) (determined as total plasma doxorubicin) during treatment course 1 and course 2.~Geometric mean (gMean) and Geometric coefficient of Variation (gCV) were not calculable for treatment course 1 as for only 2 patients evaluable concentrations were available." (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 25h, 27h, 30h, 34h, 48h, 168h, 336h and 480h after drug administration

,
Interventionµg*h/mL (Geometric Mean)
Treatment Course 1 (200mg:N=NA; All Patients:N=8)Treatment Course 2 (200mg:N=3; All Patients:N=10)
All Patients22302210
Nintedanib 200mgNA2060

[back to top]

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Nintedanib

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of nintedanib during course 1 and course 2. (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 1 hour (h) 2h, 3h, 4h, 6h, 8h, 10h, 24h, 144h, 312h and 456h after drug administration

,
Interventionng*h/mL (Geometric Mean)
Treatment Course 1 (150mg: N=6; 200mg: N=11)Treatment Course 2 (150mg: N=8; 200mg: N=7)
Nintedanib 150mg283406
Nintedanib 200mg422476

[back to top]

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Carboplatin (Determined as Ultrafilterable Platinum)

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of carboplatin during course 1 and course 2 (determined as ultrafilterable platinum). (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 25h, 26h, 27h, 28h, 30h, 32h, and 34h after drug administration

,
Interventionng*h/mL (Geometric Mean)
Treatment Course 1 (200mg:N=9; All Patients:N=16)Treatment Course 2 (200mg:N=6; All Patients:N=15)
All Patients5380055700
Nintedanib 200mg5850056200

[back to top]

Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Drug Concentration (AUC0-tz) of Carboplatin (Determined as Total Platinum)

Area under the plasma concentration-time curve from time zero to the time of the last quantifiable drug concentration (AUC0-tz) of carboplatin during course 1 and course 2 (determined as total platinum). (NCT01314105)
Timeframe: 5 minutes (min) before drug administration and 30 min,59 min, 1 hour (h) 15 min, 1h 29min, 1h 45min, 2h 15min, 2h 45min, 4h, 6h, 7h 30min, 9h, 23h 55min, 26h, 28h, 32h, 48h, 168h, 336h and 480h after drug administration

,
Interventionng*h/mL (Geometric Mean)
Treatment Course 1 (200mg:N=10; All Patients:N=16)Treatment Course 2 (200mg:N=7; All Patients:N=16)
All Patients220000260000
Nintedanib 200mg223000258000

[back to top]

Percentage of Participants With Overall Response Rate (ORR)

ORR was defined as is the proportion of participants with a best overall response of CR or PR. CR is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response. PR is > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions. (NCT01317615)
Timeframe: 3 months

InterventionPercentage of participants (Number)
RAD001 Plus Paclitaxel/Carboplatin44.9

[back to top]

Percentage of Participants With Disease Control Rate (DCR)

DCR was defined as is the percentage of participants with a best overall response of CR or PR or SD. Complete response (CR) is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR) is > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; and Progressive disease (PD is: > 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm. (NCT01317615)
Timeframe: 3 months

InterventionPercentage of participants (Number)
RAD001 Plus Paclitaxel/Carboplatin73.5

[back to top]

Progression Free Survival (PFS)

PFS was defined as the time from the date of start of treatment to date of event defined as the first documented progression or death due to any cause. (NCT01317615)
Timeframe: 6 months

InterventionDays (Median)
RAD001 Plus Paclitaxel/Carboplatin132

[back to top]

Percentage of Participants Progression-free

Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST) to determine progression-free status. Complete response (CR) is disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR) is > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD) is neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; and Progressive disease (PD is: > 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm. (NCT01317615)
Timeframe: 6 months

InterventionPercentage of participants (Number)
RAD001 Plus Paclitaxel/Carboplatin8.2

[back to top]

Percentage of Participants Progression-free

Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST) to determine progression-free status. Complete response (CR): disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR): > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; Progressive disease (PD): > 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm. (NCT01317615)
Timeframe: 3 months

InterventionPercentage of participants (Number)
RAD001 Plus Paclitaxel/Carboplatin49.0

[back to top]

Overall Survival (OS)

OS was defined as the time from date of start of treatment to date of death due to any cause. (NCT01317615)
Timeframe: 12 months

InterventionDays (Median)
RAD001 Plus Paclitaxel/Carboplatin298

[back to top]

pCR Compared Among Non-responders Between Induction Treatment Arms if Treatment Regimens Are Found to be Efficacious

"A Complete Pathological Response (pCR) is defined as having no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor. A non-responder was defined as having a PET/CT SUV (standard uptake value) decrease of less than 35% after induction.>~>>>~>~>>> Among the patients who completed induction therapy and did not respond, the percentage of patients reporting a pCR in each arm were compared." (NCT01333033)
Timeframe: Up to 5 years

Interventionpercentage of participants with a pCR (Number)
FOLFOX Regimen Non-Responders17.95
CP (Carboplatin + Paclitaxel + Radiation) Non-Responders20

[back to top]

pCR Compared Between Induction Treatment Arms Among PET/CT Responders

"A PET/CT response to induction therapy is defined as metabolic activity of the tumor decreasing by >=35%, as>~>>~>>~>> measured by maximum standardized uptake value (SUVmax). A pCR is defined as having no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor." (NCT01333033)
Timeframe: Up to 5 years

Interventionpercentage of participants with a pCR (Number)
FOLFOX Responder40.28
CP (Carboplatin + Paclitaxel + Radiation) Responder14.06

[back to top]

PET/CT Response Between Treatment Arms

A PET/CT response to induction therapy is defined as metabolic activity of the tumor decreasing by >=35%, as measured by maximum standardized uptake value (SUVmax). (NCT01333033)
Timeframe: Up to 5 years

Interventionpercentage of patients with a response (Number)
FOLFOX Regimen64.86
CP (Carboplatin + Paclitaxel + Radiation)56.14

[back to top]

Progression Free Survival (PFS) Among PET/CT Non-responders Within Each Induction Treatment Group

"A non-responder was defined as having a PET/CT SUV (standard uptake value) decrease of less than 35% after induction.~Among the patients who completed induction therapy and did not respond, the progression free survival in each arm were compared. PFS will be measured from study entry until documented progression or death from any cause. PFS will be estimated using the method of Kaplan and Meier." (NCT01333033)
Timeframe: Up to 5 years

Interventionmonths (Median)
FOLFOX Regimen Non-ResponderNA
CP Non-Responder33.4

[back to top]

Complete Pathological Response (pCR) of PET/CT Non-responders

The primary endpoint of this study is the percentage of PET/CT non-responders within each induction treatment group reporting a pCR. A pCR is defined as having no tumor found on pathology review at surgery in all resected lymph nodes and tissue. All tissues sampled must have NO viable tumor. (NCT01333033)
Timeframe: Up to 5 years

Interventionpercentage of participants with a pCR (Number)
FOLFOX Non-Responder17.95
CP Non-Responder20

[back to top]

Progression-free Survival

Documented radiographic response per Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by imaging: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. criteria each year, until subject death (NCT01344824)
Timeframe: 1400 days

Interventionmonths (Median)
Single Arm Trial12.6

[back to top]

Subjects Experiencing Toxicity

Toxicity will be evaluated using CTCAE criteria, version 3, all grade 3 and 4 events. (NCT01344824)
Timeframe: 90 days

Interventionparticipants (Number)
DiarrheaDyspnea (shortness of breath)Fatigue (asthenia, lethargy, malaise)HemoglobinHypertensionLeukocytes (total white blood cell count)LymphopeniaNauseaNeutrophils/granulocytes (ANC/AGC)Joint painPlateletsVomiting
Bevacizumab, Carboplatin, and Pemetrexed Disodium, With Option326662427222

[back to top]

Overall Survival

Time of enrollment to date of death. (NCT01344824)
Timeframe: 1400 days

Interventionmonths (Median)
Single Arm Trial20.3

[back to top]

Part 2: Median Progression-free Survival (PFS) in Weeks Based on Enhanced Response Evaluation Criteria In Solid Tumors Version 1.1 (Enhanced RECIST 1.1) by Independent Radiology Review

PFS was defined as the time from randomization to progressive disease (based on blinded independent central radiologic review) or death, whichever occurred earlier. Tumor response was evaluated every 6 weeks during treatment by diagnostic anatomic imaging and objective response assessments were performed based on enhanced RECIST 1.1 criteria. According to enhanced RECIST 1.1, progressive disease was the appearance of one or more new lesions, OR an unambiguous increase in the sum of target lesion volumes with both 1) >20% increase in the sum of volumes (SOV) of all target lesions (taking as reference the nadir) and 2) greater than two times the variability of the measurements estimated by the sponsor and/or its designees. PFS was analyzed for Part 2 participants only using the Kaplan-Meier method and median PFS was reported in weeks. Per protocol, Part 1 participants were not included in this analysis. (NCT01357161)
Timeframe: Up to 57 months

Interventionweeks (Median)
Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin34.14
Part 2: Placebo + Paclitaxel +Carboplatin31.86

[back to top]

Part 1: Objective Response Rate (ORR) Per Gynecological Cancer Intergroup (GCIG) Criteria Based on Both RECIST 1.1 and Cancer Antigen 125 (CA-125) Level by Independent Radiology Review

ORR was defined as the percentage of participants whose best response was confirmed partial response (PR) or complete response (CR) based both on imaging per RECIST 1.1 and on serum marker CA-125 level according to GCIC criteria. CR was defined by RECIST 1.1 as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm. PR was defined by RECIST 1.1 as at least a 30% decrease in the sum of the diameters (SOD) of target lesions, taking as reference the baseline SOD. A response according to CA-125 had occurred if there was ≥50% reduction in CA-125 levels from a pretreatment sample. The response must have been confirmed and maintained for at least 28 days. Participants could be evaluated according to CA-125 only if they had a pretreatment sample that was ≥2 times the upper limit of normal and within 2 weeks prior to starting treatment. Only evaluable Part 1 participants were included in this analysis. (NCT01357161)
Timeframe: Up to 57 months

Interventionpercentage of participants (Number)
Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin75.00

[back to top]

Part 1: Number of Participants With a Dose Limiting Toxicity (DLT)

DLTs assessed during first 21-day cycle of Part 1 and defined as toxicities that met pre-defined severity criteria, were possibly, probably, or definitely related to triplet therapy, and could possibly result in a change in the given dose. Hematologic DLTs included Grade (Gr) 3 or Gr 4 neutropenia with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment, and any Gr 4-5 hematological toxicity EXCEPT Gr 4 anemia, leukopenia, lymphopenia, neutropenia lasting <7 days, and thrombocytopenia lasting <4 days, except if a platelet transfusion was required. Non-hematologic DLT defined as any Gr 3, 4, or 5 nonhematologic toxicity EXCEPT: Gr 3 nausea, vomiting, diarrhea, or dehydration judged by Investigator and SPONSOR to occur in setting of inadequate compliance with supportive care measures and last for less than 48 hours, alopecia of any grade, inadequately treated hypersensitivity reactions, or clinically non-significant, treatable or reversible lab abnormalities. (NCT01357161)
Timeframe: During Cycle 1 of Part 1 (first 21 days)

Interventionparticipants (Number)
TotalFebrile neutropeniaNeutropeniaThrombocytopenia
Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin3111

[back to top]

Parts 1 and 2: Percentage of Participants That Experienced an Adverse Event (AE)

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The percentage of participants that experienced at least one AE was reported for each treatment arm. (NCT01357161)
Timeframe: Part 1: Day 1 through Post Study (286 days total). Part 2: Day 1 through Post Study (479 days total)

Interventionpercentage of participants (Number)
Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin100.0
Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin100.0
Part 2: Placebo + Paclitaxel +Carboplatin96.7

[back to top]

Parts 1 and 2: Percentage of Participants That Discontinued Study Treatment Due to an AE

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's products, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the SPONSOR's product was also an AE. The percentage of participants that discontinued study treatment (paclitaxel, carboplatin, or MK-1775) due to an AE was reported for each treatment arm. (NCT01357161)
Timeframe: Part 1: Day 1 through Post Study (286 days total). Part 2: Day 1 through Post Study (479 days total)

Interventionpercentage of participants (Number)
Part 1: MK-1775 225 mg + Paclitaxel +Carboplatin20.0
Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin20.3
Part 2: Placebo + Paclitaxel +Carboplatin21.7

[back to top]

Part 2: Median PFS in Weeks Based on RECIST 1.1 by Independent Radiology Review

PFS was defined as the time from randomization to progressive disease (based on blinded independent central radiologic review) or death, whichever occurred earlier. Tumor response was evaluated every 6 weeks during treatment by diagnostic anatomic imaging and objective response assessments were performed based on RECIST 1.1 criteria. According to RECIST 1.1, progressive disease was the appearance of one or more new lesions, OR a ≥20% increase in the sum of target lesion diameters (SOD) taking as reference the nadir (smallest SOD recorded since treatment started). PFS was analyzed for all randomized participants in Part 2 using the Kaplan-Meier method and median PFS was reported in weeks. Per protocol, Part 1 participants were not included in this analysis. (NCT01357161)
Timeframe: Up to 57 months

Interventionweeks (Median)
Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin42.86
Part 2: Placebo + Paclitaxel +Carboplatin34.86

[back to top]

Part 2: Median Overall Survival (OS) in Months

OS was defined as the time from randomization to death due to any cause, reported in months. Participants without documented death at the time of analysis were censored at the date last known to be alive. For this endpoint, all randomized participants in Part 2 were analyzed. Per protocol, Part 1 participants were not evaluated for OS. (NCT01357161)
Timeframe: Up to 57 months

Interventionmonths (Median)
Part 2: MK-1775 225 mg + Paclitaxel +CarboplatinNA
Part 2: Placebo + Paclitaxel +CarboplatinNA

[back to top]

Part 2: ORR Per GCIG Criteria Based on Both Enhanced RECIST 1.1 and CA125 Level by Independent Radiology Review

ORR defined as the percentage of participants with best response of confirmed PR or CR based both on imaging per enhanced RECIST 1.1 and on serum marker CA-125 level according to GCIC criteria. CR defined by enhanced RECIST 1.1 as disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have had reduction in short axis to <10 mm. PR was defined by enhanced RECIST 1.1 as ≥30% decrease in SOV of target lesions, taking as reference baseline SOV. Response according to CA-125 had occurred if there was ≥50% reduction in CA-125 levels from pretreatment sample. Response must have been confirmed and maintained for ≥28 days. Participants could be evaluated according to CA-125 only if they had a pretreatment sample that was ≥2 times the upper limit of normal and within 2 weeks prior to starting treatment. All randomized participants in Part 2 were analyzed. Per protocol, Part 1 participants were not included in this analysis. (NCT01357161)
Timeframe: Up to 57 months

Interventionpercentage of participants (Number)
Part 2: MK-1775 225 mg + Paclitaxel +Carboplatin74.58
Part 2: Placebo + Paclitaxel +Carboplatin69.35

[back to top]

Percentage of Participants With Primary Cardiac Event

Primary cardiac event was defined as either: Heart Failure (New York Heart Association [NYHA] Class III or IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction (EF) points from baseline and to below 50 percent (%); or cardiac death. Cardiac death was defined as either definite cardiac death: due to heart failure, myocardial infarction, or documented primary arrhythmia; or probable cardiac death: sudden unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology. (NCT01358877)
Timeframe: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)

,
Interventionpercentage of participants (Number)
Primary Cardiac Event (Composite)Heart Failure and LVEF DeclineCardiac Death (Definite or Probable)
Pertuzumab + Trastuzumab + Chemotherapy0.70.60.1
Placebo + Trastuzumab + Chemotherapy0.30.20.1

[back to top]

Peak Serum Concentration (Cmax) of Pertuzumab

(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)

Interventionmcg/mL (Mean)
Cycle 1Cycle 10Cycle 15
Pertuzumab + Trastuzumab + Chemotherapy237222206

[back to top]

Cmin of Trastuzumab

(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)

,
Interventionmcg/mL (Mean)
Cycle 1Cycle 10Cycle 15
Pertuzumab + Trastuzumab + Chemotherapy32.165.072.9
Placebo + Trastuzumab + Chemotherapy34.168.471.0

[back to top]

Cmax of Trastuzumab

(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)

,
Interventionmcg/mL (Mean)
Cycle 1Cycle 10Cycle 15
Pertuzumab + Trastuzumab + Chemotherapy180219187
Placebo + Trastuzumab + Chemotherapy190225234

[back to top]

Change From Baseline in LVEF to Worst Post-Baseline Value

LVEF is the fraction of blood (in percent) pumped out of the heart's left ventricular chamber with each heart beat, and is a measure of cardiac output for the heart. Baseline LVEF value and the maximum absolute decrease (worst value) in LVEF measurement from baseline were reported. LVEF was measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan. (NCT01358877)
Timeframe: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)

,
Interventionpercentage of blood pumped out (Mean)
BaselineChange to Worst Value
Pertuzumab + Trastuzumab + Chemotherapy65.2-7.5
Placebo + Trastuzumab + Chemotherapy65.3-7.6

[back to top]

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) Global Health Status (GHS) Scale Score

EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall quality of life (QOL) in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea and vomiting [N/V], constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, used 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 global scores were linearly transformed on a scale of 0 to 100, with a high score indicating better GHS/QOL. Negative change from Baseline values indicated deterioration in QOL or functioning and positive values indicated improvement. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; end of treatment (EOT, 28 days after the last dose, up to Week 56); Follow-up (FU) Months 18, 24, 36

,
Interventionunits on a scale (Mean)
BaselineChange at Week 13Change at Week 25Change at EOTChange at FU Month 18Change at FU Month 24Change at FU Month 36
Pertuzumab + Trastuzumab + Chemotherapy72.9-11.2-4.4-3.11.92.22.8
Placebo + Trastuzumab + Chemotherapy72.5-10.2-2.9-1.11.32.41.8

[back to top]

Change From Baseline in European Organisation for Research and Treatment of Cancer - Breast Cancer Module Quality of Life (EORTC QLQ-BR23) Functional Scale Score

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for functional scale indicated high/better level of functioning/healthy functioning. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionunits on a scale (Mean)
Baseline: Body ImageChange at Week 13: Body ImageChange at Week 25: Body ImageChange at EOT: Body ImageChange at FU Month 18: Body ImageChange at FU Month 24: Body ImageChange at FU Month 36: Body ImageBaseline: Sexual EnjoymentChange at Week 13: Sexual EnjoymentChange at Week 25: Sexual EnjoymentChange at EOT: Sexual EnjoymentChange at FU Month 18: Sexual EnjoymentChange at FU Month 24: Sexual EnjoymentChange at FU Month 36: Sexual EnjoymentBaseline: Sexual FunctionChange at Week 13: Sexual FunctionChange at Week 25: Sexual FunctionChange at EOT: Sexual FunctionChange at FU Month 18: Sexual FunctionChange at FU Month 24: Sexual FunctionChange at FU Month 36: Sexual FunctionBaseline: FPChange at Week 13: FPChange at Week 25: FPChange at EOT: FPChange at FU Month 18: FPChange at FU Month 24 : FPChange at FU Month 36: FP
Pertuzumab + Trastuzumab + Chemotherapy79.7-12.9-7.6-4.9-0.10.51.754.0-16.5-11.9-10.7-4.2-6.0-5.319.6-5.6-2.6-1.02.52.82.651.33.16.37.712.913.714.7
Placebo + Trastuzumab + Chemotherapy78.9-13.9-7.3-6.0-1.30.10.755.0-13.1-7.9-8.0-6.7-5.0-6.020.8-6.6-2.3-1.41.41.81.650.51.85.46.910.512.913.6

[back to top]

Change From Baseline in EORTC QLQ-C30 Functioning Subscale Scores

EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 functioning scores were linearly transformed on a scale of 0 to 100, with a high score indicating better functioning/support. Negative change from Baseline values indicated deterioration in functioning and positive values indicated improvement. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionunits on a scale (Mean)
Baseline: PhysicalChange at Week 13: PhysicalChange at Week 25: PhysicalChange at EOT: PhysicalChange at FU Month 18: PhysicalChange at FU Month 24: PhysicalChange at FU Month 36: PhysicalBaseline: RoleChange at Week 13: RoleChange at Week 25: RoleChange at EOT: RoleChange at FU Month 18: RoleChange at FU Month 24: RoleChange at FU Month 36: RoleBaseline: SocialChange at Week 13: SocialChange at Week 25: SocialChange at EOT: SocialChange at FU Month 18: SocialChange at FU Month 24: SocialChange at FU Month 36: SocialBaseline: CognitiveChange at Week 13: CognitiveChange at Week 25: CognitiveChange at EOT: CognitiveChange at FU Month 18: CognitiveChange at FU Month 24: CognitiveChange at FU Month 36: CognitiveBaseline: EmotionalChange at Week 13: EmotionalChange at Week 25: EmotionalChange at EOT: EmotionalChange at FU Month 18: EmotionalChange at FU Month 24: EmotionalChange at FU Month 36: Emotional
Pertuzumab + Trastuzumab + Chemotherapy89.6-10.7-4.6-4.1-0.9-0.4-0.379.8-8.0-0.70.46.17.37.981.9-8.7-2.20.05.05.56.688.8-9.1-7.6-7.7-6.1-6.2-5.472.83.35.15.67.77.87.8
Placebo + Trastuzumab + Chemotherapy89.1-10.6-4.3-3.2-0.9-0.3-0.179.4-8.50.42.35.76.97.680.6-7.8-0.71.24.86.57.187.9-9.0-7.0-7.2-5.8-5.5-4.971.32.95.96.27.68.58.4

[back to top]

Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3

The Kaplan-Meier approach was used to estimate the percentage of participants who were alive at 3 years. (NCT01358877)
Timeframe: 3 years

InterventionEstimate of percentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy97.65
Placebo + Trastuzumab + Chemotherapy97.67

[back to top]

Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores

EORTC QLQ-C30 is a cancer-specific instrument with 30 questions used to assess the overall QOL in cancer participants. First 28 questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, social, cognitive, emotional), 8 symptom scales/items (diarrhea, fatigue, dyspnea, appetite loss, insomnia, N/V, constipation, and pain) and a single item (financial difficulties). Last 2 questions represented participant's assessment of overall health and quality of life, coded on 7-point scale (1=very poor to 7=excellent). EORTC QLQ-C30 financial difficulties scores were linearly transformed on a scale of 0 and 100, with a high score indicating a higher level of financial difficulties. Negative change from Baseline values indicated improvement in financial difficulties and positive values indicated worsening of financial difficulties. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionunits on a scale (Mean)
BaselineChange at Week 13Change at Week 25Change at EOTChange at FU Month 18Change at FU Month 24Change at FU Month 36
Pertuzumab + Trastuzumab + Chemotherapy20.33.12.3-0.2-4.1-5.2-7.1
Placebo + Trastuzumab + Chemotherapy22.11.7-0.3-1.5-5.1-6.9-8.3

[back to top] [back to top]

Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective [FP]) and four symptom scales (systemic side effects [SE], upset by hair loss, arm symptoms, breast symptoms). Questions used 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much). Scores averaged and transformed to 0-100 scale. High score for symptom scale indicated high level of symptomatology/problems/greater degree of symptoms. Negative change from Baseline indicated deterioration in QOL and positive change from Baseline indicated an improvement in QOL. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionunits on a scale (Mean)
Baseline:Systemic SEChange at Week 13: Systemic SEChange at Week 25: Systemic SEChange at EOT: Systemic SEChange at FU Month 18: Systemic SEChange at FU Month 24: Systemic SEChange at FU Month 36: Systemic SEBaseline: Hair LossChange at Week 13: Hair LossChange at Week 25: Hair LossChange at EOT: Hair LossChange at FU Month 18: Hair LossChange at FU Month 24: Hair LossChange at FU Month 36: Hair LossBaseline: Arm SymptomsChange at Week 13: Arm SymptomsChange at Week 25: Arm SymptomsChange at EOT: Arm SymptomsChange at FU Month 18: Arm SymptomsChange at FU Month 24: Arm SymptomsChange at FU Month 36: Arm SymptomsBaseline: Breast SymptomsChange at Week 13: Breast SymptomsChange at Week 25: Breast SymptomsChange at EOT: Breast SymptomsChange at FU Month 18: Breast SymptomsChange at FU Month 24: Breast SymptomsChange at FU Month 36: Breast Symptoms
Pertuzumab + Trastuzumab + Chemotherapy9.521.19.28.34.44.14.526.417.38.310.9-7.0-4.1-5.621.6-4.7-2.9-3.5-4.0-5.1-5.919.5-5.01.9-0.6-3.0-6.4-7.3
Placebo + Trastuzumab + Chemotherapy10.221.78.27.55.54.95.222.121.214.517.93.20.72.421.7-2.1-2.3-3.4-3.9-5.0-4.720.4-5.2-0.4-3.8-5.9-7.3-7.9

[back to top]

Percentage of Participants With Secondary Cardiac Event

Secondary cardiac event was defined as asymptomatic or mildly symptomatic (NYHA Class II) significant drop in LVEF (defined as an absolute decrease of at least 10 EF points from baseline and to below 50%), confirmed by a second LVEF assessment within approximately three weeks of the first significant LVEF assessment or confirmed by the Cardiac Advisory Board (CAB). (NCT01358877)
Timeframe: Baseline until data cut-off date 19 December 2016 (up to maximum length of follow-up of 59 months)

Interventionpercentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy2.7
Placebo + Trastuzumab + Chemotherapy2.8

[back to top]

Percentage of Participants With Recurrence-Free Interval (RFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Percentage of participants with RFI event is reported. RFI event was defined as local, regional or distant breast cancer recurrence. (NCT01358877)
Timeframe: Randomization until local, regional or distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Interventionpercentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy5.8
Placebo + Trastuzumab + Chemotherapy7.2

[back to top]

Percentage of Participants With IDFS Event (Including SPNBC), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Percentage of participants with IDFS events (including SPNBC) is reported. IDFS-SPNBC event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). (NCT01358877)
Timeframe: Randomization to the first occurrence of IDFS event (including SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Interventionpercentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy7.9
Placebo + Trastuzumab + Chemotherapy9.6

[back to top]

Percentage of Participants With Distant Recurrence-Free Interval (DRFI) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Percentage of participants with DRFI event is reported. DRFI event was defined as distant breast cancer recurrence. (NCT01358877)
Timeframe: Randomization until distant breast cancer recurrence (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Interventionpercentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy5.0
Placebo + Trastuzumab + Chemotherapy6.0

[back to top]

Percentage of Participants With Disease-Free Survival (DFS) Event, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Percentage of participants with DFS event is reported. DFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS. (NCT01358877)
Timeframe: Randomization to the first occurrence of DFS event (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Interventionpercentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy8.0
Placebo + Trastuzumab + Chemotherapy9.8

[back to top]

Percentage of Participants With Invasive Disease-Free Survival (IDFS) Event (Excluding Second Primary Non-Breast Cancer [SPNBC]), as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Percentage of participants with IDFS events (excluding SPNBC) is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (that is [i.e.], an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including ductal carcinoma in situ [DCIS] and lobular carcinoma in situ [LCIS]) and non-melanoma skin cancer were excluded as an event. (NCT01358877)
Timeframe: Randomization to the first occurrence of IDFS event (excluding SPNBC) (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Interventionpercentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy7.1
Placebo + Trastuzumab + Chemotherapy8.7

[back to top]

Percentage of Participants Who Died

Percentage of participants who died due to any cause is reported. (NCT01358877)
Timeframe: Randomization until death due to any cause (until data cut-off date 19 December 2016, up to maximum length of follow-up of 59 months)

Interventionpercentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy3.3
Placebo + Trastuzumab + Chemotherapy3.7

[back to top]

Trough Serum Concentration (Cmin) of Pertuzumab

(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)

Interventionmicrograms per milliliter (mcg/mL) (Mean)
Cycle 1Cycle 10Cycle 15
Pertuzumab + Trastuzumab + Chemotherapy68.088.195.5

[back to top]

Kaplan-Meier Estimate of the Percentage of Participants Who Were RFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Kaplan-Meier estimate of the percentage of participants who were RFI event-free at Year 3 is reported. RFI event was defined as local, regional or distant breast cancer recurrence. (NCT01358877)
Timeframe: 3 years

InterventionEstimate of percentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy95.18
Placebo + Trastuzumab + Chemotherapy94.27

[back to top]

Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Including SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (including SPNBC) at Year 3 is reported. IDFS-SPNBC was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC (with the exception of non-melanoma skin cancers and in situ carcinoma of any site). (NCT01358877)
Timeframe: 3 years

InterventionEstimate of percentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy93.50
Placebo + Trastuzumab + Chemotherapy92.51

[back to top]

Kaplan-Meier Estimate of the Percentage of Participants Who Were IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Kaplan-Meier estimate of the percentage of participants who were IDFS event-free (excluding SPNBC) at Year 3 is reported. IDFS event was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer. All SPNBCs and in situ carcinomas (including DCIS and LCIS) and non-melanoma skin cancer were excluded as an event. (NCT01358877)
Timeframe: 3 years

InterventionEstimate of percentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy94.06
Placebo + Trastuzumab + Chemotherapy93.24

[back to top]

Kaplan-Meier Estimate of the Percentage of Participants Who Were DRFI Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Kaplan-Meier estimate of the percentage of participants who were DRFI event-free at Year 3 is reported. DRFI event was defined as distant breast cancer recurrence. (NCT01358877)
Timeframe: 3 years

InterventionEstimate of percentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy95.70
Placebo + Trastuzumab + Chemotherapy95.13

[back to top]

Kaplan-Meier Estimate of the Percentage of Participants Who Were DFS Event-Free at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings

Kaplan-Meier estimate of the percentage of participants who were DFS event-free at Year 3 is reported. DFS was defined as the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence (i.e., an invasive breast cancer involving the same breast parenchyma as the original primary lesion); ipsilateral local-regional invasive breast cancer recurrence (i.e., an invasive breast cancer in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); distant recurrence (i.e., evidence of breast cancer in any anatomic site - other than the two above mentioned sites); death attributable to any cause; contralateral invasive breast cancer; SPNBC or contralateral or ipsilateral DCIS. (NCT01358877)
Timeframe: 3 years

InterventionEstimate of percentage of participants (Number)
Pertuzumab + Trastuzumab + Chemotherapy93.42
Placebo + Trastuzumab + Chemotherapy92.29

[back to top]

Percentage of Participants With Response for EQ-5D-3L Questionnaire: Anxiety/Depression Domain

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in anxiety/depression domain was reported: I am not anxious or depressed; I am moderately anxious or depressed; and I am extremely anxious or depressed. Response percentages may not add up to 100% due to data rounding. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionpercentage of participants (Number)
Baseline: Not anxious/depressBaseline: Moderate anxious/depressBaseline: Extreme anxious/depressWeek 13: Not anxious/depressWeek 13: Moderate anxious/depressWeek 13: Extreme anxious/depressWeek 25: No anxious/depressWeek 25: Moderate anxious/depressWeek 25: Extreme anxious/depressEOT: Not anxious/depressEOT: Moderate anxious/depressEOT: Extreme anxious/depressFU Month 18: Not anxious/depressFU Month 18: Moderate anxious/depressFU Month 18: Extreme anxious/depressFU Month 24: Not anxious/depressFU Month 24: Moderate anxious/depressFU Month 24: Extreme anxious/depressFU Month 36: Not anxious/depressFU Month 36: Moderate anxious/depressFU Month 36: Extreme anxious/depress
Pertuzumab + Trastuzumab + Chemotherapy47.149.43.553.643.43.055.541.92.558.538.92.661.436.22.463.833.82.464.033.32.6
Placebo + Trastuzumab + Chemotherapy44.750.15.252.444.03.755.541.82.758.339.12.659.937.03.161.036.22.861.635.43.0

[back to top]

Percentage of Participants With Response for EQ-5D-3L Questionnaire: Pain/Discomfort Domain

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in pain/discomfort domain was reported: I have no pain or discomfort; I have moderate pain or discomfort; and I have extreme pain or discomfort. Response percentages may not add up to 100% due to data rounding. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionpercentage of participants (Number)
Baseline: No pain/discomfortBaseline: Moderate pain/discomfortBaseline: Extreme pain/discomfortWeek 13: No pain/discomfortWeek 13: Moderate pain/discomfortWeek 13: Extreme pain/discomfortWeek 25: No pain/discomfortWeek 25: Moderate pain/discomfortWeek 25: Extreme pain/discomfortEOT: No pain/discomfortEOT: Moderate pain/discomfortEOT: Extreme pain/discomfortFU Month 18: No pain/discomfortFU Month 18: Moderate pain/discomfortFU Month 18: Extreme pain/discomfortFU Month 24: No pain/discomfortFU Month 24: Moderate pain/discomfortFU Month 24: Extreme pain/discomfortFU Month 36: No pain/discomfortFU Month 36: Moderate pain/discomfortFU Month 36: Extreme pain/discomfort
Pertuzumab + Trastuzumab + Chemotherapy49.050.01.044.652.72.744.353.32.449.348.52.251.346.62.156.741.31.959.538.91.6
Placebo + Trastuzumab + Chemotherapy49.049.71.340.556.53.043.754.41.950.047.62.453.144.72.156.041.52.557.840.12.1

[back to top]

Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in self-care domain was reported: I have no problems with self-care; I have some problems washing or dressing myself; and I am unable to wash or dress myself. Response percentages may not add up to 100% due to data rounding. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionpercentage of participants (Number)
Baseline: No problemsBaseline: Some problemsBaseline: UnableWeek 13: No problemsWeek 13: Some problemsWeek 13: UnableWeek 25: No problemsWeek 25: Some problemsWeek 25: UnableEOT: No problemsEOT: Some problemsEOT: UnableFU Month 18: No problemsFU Month 18: Some problemsFU Month 18: UnableFU Month 24: No problemsFU Month 24: Some problemsFU Month 24: UnableFU Month 36: No problemsFU Month 36: Some problemsFU Month 36: Unable
Pertuzumab + Trastuzumab + Chemotherapy89.710.00.394.35.30.495.54.30.195.44.40.297.22.60.296.92.80.397.32.50.2
Placebo + Trastuzumab + Chemotherapy90.79.10.293.26.40.495.04.70.395.84.00.296.03.60.396.33.50.396.53.20.3

[back to top]

Percentage of Participants With Response for EQ-5D-3L Questionnaire: Usual Activities Domain

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in usual activities domain was reported: I have no problems with performing my usual activities; I have some problems with performing my usual activities; and I am unable to perform my usual activities. Response percentages may not add up to 100% due to data rounding. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionpercentage of participants (Number)
Baseline: No problemsBaseline: Some problemsBaseline: UnableWeek 13: No problemsWeek 13: Some problemsWeek 13: UnableWeek 25: No problemsWeek 25: Some problemsWeek 25: UnableEOT: No problemsEOT: Some problemsEOT: UnableFU Month 18: No problemsFU Month 18: Some problemsFU Month 18: UnableFU Month 24: No problemsFU Month 24: Some problemsFU Month 24: UnableFU Month 36: No problemsFU Month 36: Some problemsFU Month 36: Unable
Pertuzumab + Trastuzumab + Chemotherapy67.430.42.256.840.13.166.532.21.272.426.31.378.520.60.978.720.40.980.918.30.7
Placebo + Trastuzumab + Chemotherapy66.132.21.754.143.02.965.832.71.472.526.60.976.323.00.779.119.71.179.819.40.8

[back to top]

Percentage of Participants With Response for European Quality of Life-5 Dimensions-3 Level (EQ-5D-3L) Questionnaire: Mobility Domain

EQ-5D-3L is a descriptive system of health-related quality of life states consisting of 5 dimensions/domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each of which has 3 levels of severity (no problems [scored as 1], some or moderate problems [scored as 2], and extreme problems [scored as 3]). Percentage of participants with each of the following responses in mobility domain was reported: I have no problems in walking about; I have some problems in walking about; and I am confined to bed. Response percentages may not add up to 100% due to data rounding. (NCT01358877)
Timeframe: Baseline, Weeks 13, 25; EOT (28 days after the last dose, up to Week 56); FU Months 18, 24, 36

,
Interventionpercentage of participants (Number)
Baseline: No problemsBaseline: Some problemsBaseline: Confined to bedWeek 13: No problemsWeek 13: Some problemsWeek 13: Confined to bedWeek 25: No problemsWeek 25: Some problemsWeek 25: Confined to bedEOT: No problemsEOT: Some problemsEOT: Confined to bedFU Month 18: No problemsFU Month 18: Some problemsFU Month 18: Confined to bedFU Month 24: No problemsFU Month 24: Some problemsFU Month 24: Confined to bedFU Month 36: No problemsFU Month 36: Some problemsFU Month 36: Confined to bed
Pertuzumab + Trastuzumab + Chemotherapy93.86.20.077.522.10.483.816.10.185.114.80.188.811.20.187.812.10.188.511.50.0
Placebo + Trastuzumab + Chemotherapy92.96.90.274.824.80.482.717.20.184.914.90.287.012.80.287.712.10.187.812.10.1

[back to top]

Pathological Complete Histological Response (pCR) After Resection Than Chemotherapy Alone in Patients With Resectable Carcinoma of the Esophagus and Cardia.

Chireac tumour regression grade (NCT01362127)
Timeframe: Therapy followed in 14-16 weeks before surgery. After surgery the patients will be followed until 60 weeks after completed therapy.

InterventionParticipants (Count of Participants)
Radiochemotherapy22
Chemotherapy7

[back to top]

Safety of Respective Neoadjuvant Therapies.

Safety profile of carrying out radical surgery after respective neoadjuvant therapy. (NCT01362127)
Timeframe: Five years follow up

InterventionParticipants (Count of Participants)
Radiochemotherapy79
Chemotherapy81

[back to top]

HRQOL and Swallowing Function

The European Organisation for Research and Treatment of Cancer (EORTC) core questionnaire QLQ-C30 and disease specific questionnaires (QLQ-OES24/OG25). All items included in the questionnaires are analysed and also separate analysis of dysphagia questionnaires for oesophageal cancer were used, both clinically and psychometrically validated. All questions have four response alternatives (1, not at all; 2:a little, 3: quite a bit, 4: very much), except global scales which comprise seven response alternatives from poor to excellent. Questionnaire responses were transformed lineraly into scores ranging from 0 to 100 according to the EORTC scoring manual. A higher score indicates either more symotoms or better function, depending on the question. (NCT01362127)
Timeframe: Entry study up to Five years follow up

,
Interventionunits on a scale (Mean)
Mean global QoLDysphagia score all
Chemotherapy6931
Radiochemotherapy6727

[back to top]

To Assess the Safety Profile of Trastuzumab in USPC Patients by CTCAE v4.0

To assess the safety profile of trastuzumab in USPC patients by CTCAE v4.0. Presented are counts of those that experience any Serious Adverse Events or All Other Adverse Events. (NCT01367002)
Timeframe: 6 years

,
InterventionParticipants (Count of Participants)
Serious Adverse EventsAll Other Adverse Events
Carboplatin/Paclitaxel628
Trastuzumab1432

[back to top]

Progression Free Survival Differences Between Treatment Arms.

Progression free survival differences between treatment arms. (NCT01367002)
Timeframe: 6 years

Interventionmonths (Median)
Carboplatin/Paclitaxel8.049
Trastuzumab12.945

[back to top]

To Assess Overall Survival (OS)

To assess overall survival (OS), presented are the number of participants that survived through the duration of the study period. (NCT01367002)
Timeframe: 6 years

InterventionParticipants (Count of Participants)
Carboplatin/Paclitaxel7
Trastuzumab9

[back to top]

Number of Participants With Adverse Events

Number of participants with adverse events as a measure of safety and tolerability (NCT01376310)
Timeframe: Until 30 days after the last dose of study treatment. Subjects may have continued to receive study treatment until disease progression, death, unacceptable toxicity or until locally commercially available. The maximum duration of exposure was 76 months.

,
InterventionParticipants (Count of Participants)
Adverse EventsTreatment-Related Adverse EventsSerious Adverse EventsTreatment-Related Serious Adverse Events
Cohort A (GSK1120212 < 24 Weeks)119101268
Cohort B (GSK1120212 >= 24 Weeks)3026134

[back to top]

Incidence of Serious (>= Grade 3) Adverse Events as Measured by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phase II)

Adverse Events (AEs) are reported by CTCAE Version 4.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT01386385)
Timeframe: Duration of treatment and follow up until death or 5 years post registration

,,,
InterventionParticipants (Number)
AnemiaAnorexiaDehydrationDiarrheaDysphagiaEsophageal painEsophagitisFatigueHyperglycemiaHypocalcemiaHypoglycemiaHypokalemiaHypomagnesemiaHyponatremiaHypotensionLung infectionLymphocyte count decreasedMucositis oralNauseaNeutrophil count decreasedPlatelet count decreasedPneumonitisUpper gastrointestinal hemorrhageVomitingWeight lossWhite blood cell decreased
Arm I Concurrent Chemoradiation (Veliparib, 3D-CRT, Carboplati11000111100000103103100012
Arm I Consolidation (Veliparib, Carboplatin, Paclitaxel)11112001000000002013101102
Arm II Concurrent Chemoradiation (Placebo, 3D-CRT, Carboplatin01100011011113014001010102
Arm II Consolidation (Placebo, Carboplatin, Paclitaxel)00000000100110002000010010

[back to top]

Progression-free Survival of Patients Treated With Chemoradiotherapy Plus Veliparib (Phase II)

"Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause. Participants last known to be alive are censored at date of last contact.~Assessed by Response Evaluation Criteria in Solid Tumors, RECIST 1.1" (NCT01386385)
Timeframe: The time from randomization to progression or death due to any cause, assessed up to 5 years

Interventionmonths (Median)
Arm I (RT, Veliparib, Carboplatin, Paclitaxel)9.3
Arm II (3D-CRT, Placebo, Carboplatin, Paclitaxel)9.9

[back to top]

Overall Survival (Phase II)

From date of registration to date of death due to any cause. Participants last known to be alive are censored at date of last contact. (NCT01386385)
Timeframe: Up to 5 years

Interventionmonths (Median)
Arm I (RT, Veliparib, Carboplatin, Paclitaxel)27.6
Arm II (3D-CRT, Placebo, Carboplatin, Paclitaxel)15.2

[back to top]

Objective Response Rate (Phase II)

ORR is defined as the percentage of participants with evidence of a confirmed complete response (CR) or partial response (PR) as per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (NCT01386385)
Timeframe: Up to 5 years

Interventionpercentage of participants (Number)
Arm I (RT, Veliparib, Carboplatin, Paclitaxel)56
Arm II (3D-CRT, Placebo, Carboplatin, Paclitaxel)69

[back to top]

Maximum Tolerated Dose of Veliparib When Given Concurrently With Standard Carboplatin/Paclitaxel and Radiotherapy, Determined According to Incidence of Dose Limiting Toxicity (DLT) (Phase I)

"DLTs will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. DLTs must be attributable (probably, possibly, definitely related) to the study regimen and only occur during RT or 2 weeks after completing RT.~DLTs are defined as:~Radiation esophagitis or dermatitis radiation Grade 3 that lasts > 7 consecutive days or Grade 4~Grade 4 neutropenia for > 7 days or neutropenic fever ( ANC <500 and temperature >= 38.5 oC)~Grade 4 thrombocytopenia~Grade 4 nausea/vomiting despite appropriate antiemetic therapy~Delays in radiotherapy or chemotherapy or ABT-888 due to toxicity of > 3 weeks~All other non-hematologic toxicities >= Grade 3, except~anorexia~fatigue~infection without neutropenia~Grade 3 AST/ALT elevations <= 7 days, infusion reactions~Grade 3 or 4 lymphopenia~Grade 3 or 4 electrolyte abnormalities that are corrected to <=Grade 2 in < 48 hours~Grade 3 dehydration lasting < 7 days" (NCT01386385)
Timeframe: 9 weeks

Interventiondose limiting toxicity (Number)
Phase I 40mg Veliparib1
Phase I 80mg Veliparib1
Phase I 120mg Veliparib0

[back to top]

Maximum Tolerated Dose (MTD) of Eribulin in Combination With Carboplatin and Trastuzuamb

The MTD is defined as the dose at which <= 1 of 6 subjects experience DLT (Dose Limiting Toxicity) and above which >= 2 of 6 subjects experience DLT. (NCT01388647)
Timeframe: Approximately 22 days from study treatment start, per subject

Interventionmg/m^2 (Number)
All Study Participants1.1

[back to top]

Clinical Response

Clinical assessment of response will be performed 3 weeks after completion of study treatment. The treating physician will assess clinical response using physical examination and radiologic evaluation. Clinical response options are complete response (no invasive tumor in breast and lymph nodes), partial response (> 50% reduction in longest diameter of pretreatment tumor), no response (< 50% response to 10% growth of tumor as determined by longest diameter of pretreatment tumor size), and progression. (NCT01388647)
Timeframe: Assessed prior to definitive surgery, approximately 18 weeks from study treatment start.

,
Interventionpercentage of participants (Number)
Complete ResponsePartial ResponseMissing
Eribulin 1.1 mg/m216.783.30
Eribulin 1.4 mg/m250.033.316.7

[back to top]

Dose Limiting Toxicity (DLT)

DLT is defined as grade 4 thrombocytopenia; grade 4 anemia; grade 4 neutropenia lasting > 5 days; or any grade 3 or 4 non-hematologic toxicity occurring during Cycle 1 which is attributable to eribulin, carboplatin, trastuzumab or the combination, or the inability to deliver all three agents at the assigned dose and scheduled time during Cycle 1.The following events are excluded from the DLT definition: grade 3 nausea and/or vomiting responsive to antiemetics; grade 3 fever or infection; grade 3 diarrhea responsive to antidiarrheal therapy. (NCT01388647)
Timeframe: Approximately 22 days from study treatment start, per subject

,
Interventionparticipants (Number)
Grade 4 thrombocytopeniaInability to deliver all 3 agents at assigned dose
Eribulin 1.1 mg/m210
Eribulin 1.4 mg/m212

[back to top]

Pathologic Response

Definitive surgery will be performed 3 to 8 weeks after completion of study treatment. The pathology report will be scored for pathologic response: complete pathologic response (no invasive cancer in breast or lymph nodes; residual DCIS or LCIS is acceptable), partial pathologic response (residual invasive cancer in breast and/or lymph nodes), or no response (pathologic staging is equal to or worse than pretreatment clinical staging). (NCT01388647)
Timeframe: Assessed at time of definitive surgery, approximately 21-26 weeks from study treatment start

,
Interventionpercentage of participants (Number)
Complete ResponsePartial Response
Eribulin 1.1 mg/m216.783.3
Eribulin 1.4 mg/m216.783.3

[back to top]

PHASE I: Number of Patients That Experience a Grade 3-4 Dose Limiting Toxicity

A dose limiting toxicity (DLT) will be defined as any grade 3-4 non-hematologic toxicity or increase in bilirubin >/= 2 mg/dL (>2X baseline in patients with Gilbert's syndrome), or elevation in AST/ALT > 3.0 X ULN during the first 3 week course of therapy. (NCT01395537)
Timeframe: after 9 weeks (3 cycles) of treatment

InterventionParticipants (Count of Participants)
Lapatinib With Carboplatin and Paclitaxel1

[back to top]

To Determine the Overall Survival

Overall survival is defined as the length of time between the date of starting treatment and death due to any cause. For a patient who is alive at the time of the statistical analysis, the patient will be considered censored at the last date of known contact. (NCT01395537)
Timeframe: after 37 months

Interventionweeks (Median)
Lapatinib With Carboplatin and Paclitaxel32

[back to top]

PHASE II: To Assess the Response Rate to This Regimen.

Number of patients with stable or responding disease after 6 cycles of carboplatin and paclitaxel will continue treatment with lapatinib alone until progression of disease or intolerable side effects. (NCT01395537)
Timeframe: after 37 months

InterventionParticipants (Count of Participants)
Lapatinib With Carboplatin and Paclitaxel0

[back to top]

Progression Free Survival

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter ever recorded since study treatment started, or progression in existing non-target lesions,or the appearance of one or more new lesions . (NCT01404260)
Timeframe: The evaluation of disease is demanded every two months for the patients receiving maintenance use of Gefitinib or patients in observation after chemotherapy,until disease progression occured

Interventionmonths (Median)
Arm A: Gefitinib+Gemcitabine +Carboplatin9.7
Arm B: Gemcitabine +Carboplatin4.2

[back to top]

Patient-reported Quality of Life Scores

Functional Assessment of Cancer Therapy - Head & Neck (FACT-HN) is the FACT-G and a 12 item head and neck cancer specific subscale completed at screening (Screening), 3 weeks post induction chemotherapy (Treatment Break), 7 weeks post concomitant chemoradiotherapy (7 weeks Off Treatment), one year post off-treatment (1 year Off Treatment). The FACT-G is a 27 item measure of general QOL assessing function in 4 domains: physical well-being (PWB), social-family well-being (SFWB), emotional well-being (EWB) and functional well-being (FWB). Items are rated by patients on a Likert scale from 0 to 4 (resulting in potential total scores between 0 and 156). Higher scores represent better QOL. (NCT01412229)
Timeframe: screening until one year after treatment

InterventionFACT-HN score (Median)
Pre-TreatmentTreatment Break7 weeks Off Treatment1 year Off Treatment
Treatment105.67117.0094.00116.00

[back to top]

Number of Participants With at Least One Grade 3-4 Toxicity

Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. (NCT01412229)
Timeframe: 9 Weeks

InterventionParticipants (Count of Participants)
Treatment17

[back to top]

Number of Participants With at Least One Grade 3-4 Toxicity, Listed by Event

Toxicity will be assessed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4. (NCT01412229)
Timeframe: 24 Weeks

Interventionparticipants (Number)
rashdecreased neutrophil countdecreased white blood cellsfatiguepalmar-plantar erythrodysesthesia syndromefebrile neutropeniahypocalcemiahypokalemiaanaphylaxis to C225
Treatment1142111110

[back to top]

Rate of Complete Response Following Induction Chemotherapy

Report the rate of complete responses, defined as disappearance of all target lesions, following induction chemotherapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions. (NCT01412229)
Timeframe: Baseline evaluation to 3 weeks after induction chemotherapy

InterventionParticipants (Count of Participants)
Treatment10

[back to top]

Progression Free Survival

Rate of Progression Free Survival (Time to death or progression defined by imaging of target lesions via CT or MRI scan post induction chemotherapy and chemoradiotherapy every 3 months for one year) (NCT01412229)
Timeframe: 1 year

Interventionpercentage of participants (Number)
Treatment81

[back to top]

Overall Survival

Rate of Overall Survival (NCT01412229)
Timeframe: 1 year

InterventionParticipants (Count of Participants)
Treatment34

[back to top]

Objective Response Rate (CR+PR)

Objective Response Rate as defined by RECIST 1.1 after induction chemotherapy followed by definitive chemoradiation. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective Response (OR) = CR + PR. (NCT01412229)
Timeframe: 20 weeks

InterventionParticipants (Count of Participants)
Treatment30

[back to top]

Complete Response Rate (CR)

Complete Response Rate as defined by RECIST 1.1 after induction chemotherapy followed by definitive chemoradiation (NCT01412229)
Timeframe: 20 weeks

InterventionParticipants (Count of Participants)
Treatment10

[back to top]

Progression-free Survival (PFS)

"Estimated using the product-limit method of Kaplan and Meier.~PFS defined as time from randomization to progression or death due to any cause.~Progression defined as Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions." (NCT01413750)
Timeframe: From first day of treatment to the first observation of disease progression or death due to any cause, assessed up to 1 year

Interventionmonths (Median)
Phase II: Vorinostat4.1
Phase II: Placebo7.3

[back to top]

Maximum Tolerated Dose (MTD) (Phase I)

The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity. The MTD is one dose level below the lowest dose in which 33% or more of the patients experience a DLT. The MTD is based on the first cycle of therapy. The recommended Phase II dose is generally the MTD, although secondary considerations of toxicity and dose reductions on subsequent cycles and other secondary considerations may result in the recommended Phase II dose being below the MTD. (NCT01413750)
Timeframe: 4 weeks from start of treatment, up to 1 year

Interventionmg (Number)
Phase I800

[back to top]

Dose Limiting Toxicity (DLT) (Phase I)

DLT is defined as any grade III or higher non-hematological toxicity except nausea, vomiting or alopecia. Nausea or vomiting (> grade 2) that last longer than 48 hours despite maximal medical therapy. Absolute neutrophil count < 1000/uL lasting longer than 7 days. Grade 4 thrombocytopenia (platelet < 25,000/uL). Grade 3 or 4 neutropenia associated with sepsis or fever > 38 C. Delay in starting cycle 2 by more than 2 weeks due to toxicity.Abnormal non-hematological laboratory criteria (Grade 3 or higher) will be considered a DLT, if clinically significant and drug-related. If baseline value is elevated prior to drug therapy, an increase will not be considered a DLT unless there is an elevation by more than 2 grades, and it is of clinical significance. Dose escalation schedule for vorinostat: 600 mg QD; 800 mg QD. (NCT01413750)
Timeframe: 4 weeks from start of treatment, up to 1 year

Interventionparticipants with DLTs (Number)
Phase I: Dose Level 11
Phase I: Dose Level 20

[back to top]

Patterns of Disease Recurrence

Number of patients for the site of disease recurrence. Disease was considered as persistent if participant had evidence of disease at study entry and disease did not progress during study. Disease status was considered locoregional alone if a participant had disease progression in the pelvis region including vagina after study entry. Disease status was considered distant if a participant had disease progression outside the pelvis (for example the abdomen and lung) after study entry. Criteria used to determine the no progression group includes participants that expired without documentation of progression. (NCT01414608)
Timeframe: through study completion an average of 60 months

,
Interventionparticipants (Number)
PersistentLocoregional aloneDistant with or without locoregionalOther/UnknownNo Progression recorded
Standard Chemoradiation15335153304
Standard Chemoradiation With Adjuvant Chemotherapy5474237332

[back to top]

Radiation Protocol Compliance

Radiation protocol compliance measured by external beam dose delivered (NCT01414608)
Timeframe: Average duration of 7 weeks

InterventionGray (Mean)
Arm A45.6
Arm B45.7

[back to top]

Quality of Life for Global Health Status

Quality of Life measured by change of global health status score from baseline to 12 months follow-up. A cancer-specific questionnaire with 30 items which summarize as five functioning scales, a global health status/quality of life scale, three symptom scales and six single items assessing additional symptoms and perceived financial impact. The minimum global health status score was 0 and the maximum global health status score was 100. A higher global health status score means better outcome. (NCT01414608)
Timeframe: Baseline and 12 months

Interventionscore on a scale (Mean)
Standard Chemoradiation1.7
Standard Chemoradiation With Adjuvant Chemotherapy2.4

[back to top]

Progression-free Survival Rate at 5 Years

Estimate for probability of progression free at 5 years by Kaplan-Meier method, where progression-free survival is defined as the time from randomization to the time of disease progression, death from any cause or date of last contact, whichever occurs first. Disease progression is defined by increasing clinical, radiological or pathological evidence of disease from participant entry to when investigator deems a progression. RECIST V1.0 was not used to determine response on this study. (NCT01414608)
Timeframe: 5 years from study randomization

InterventionPercentage of participants (Number)
Standard Chemoradiation62
Standard Chemoradiation With Adjuvant Chemotherapy63

[back to top]

Overall Survival Rate at 5 Years

Estimate for probability of overall survival at 5 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first. (NCT01414608)
Timeframe: 5 years from study randomization

InterventionPercentage of participants (Number)
Standard Chemoradiation71
Standard Chemoradiation With Adjuvant Chemotherapy72

[back to top]

Number of Participants With Adverse Events (Grade 3 or Higher) in First Year

Number of participants with a maximum grade of 3 or higher for pre-specified adverse events that occurred during the first year after randomization. Adverse events are graded and categorized using CTCAE v4.0. (NCT01414608)
Timeframe: 1 year after randomization

,
InterventionParticipants (Count of Participants)
Abdominal painAlanine aminotransferase increasedAllergic reaction/hypersensitivityAlopeciaAnemiaAspartate aminotransferase increasedColitisColonic obstructionCreatinine IncreasedCystitis noninfectiveDehydrationDermatitis radiationDiarrheaEnterocolitisFatigueFebrile NeutropeniaFemale genital tract fistulaHearing impairedHemorrhage bladderHemorrhage rectumLymphocyte count decreasedMucositis oralMyalgiaNauseaNeutrophil count decreasedPain in extremityPelvic painPerineal painPeripheral motor neuropathyPeripheral sensory neuropathyPlatelet count decreasedProctitisSmall intestinal obstructionThrombosis/Thrombus/EmbolismTumor painUrinary tract painUterine obstructionVaginal DrynessVaginal painVaginal strictureVomiting
Standard Chemoradiation13410323213113121279403120820113331110152176110349
Standard Chemoradiation With Adjuvant Chemotherapy142216422133912039914302110311711604161604700211415

[back to top]

Overall Survival (OS)

Overall survival (OS) was assessed through 24 months. The outcome is reported as the median time that participants remained alive, with 95% CI. (NCT01437449)
Timeframe: 24 months

Interventionmonths (Median)
Cisplatin + Docetaxel + Cetuximab14.7

[back to top] [back to top]

Progression-free Survival (PFS)

"Progression-free survival (PFS), defined as the duration of time from start of treatment to time of progression or death, was assessed through 24 months, according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. The outcome is reported as the median time that participants remained free of progression, with 95% confidence interval (CI).~Complete Response (CR) = Disappearance of all target lesions~Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions~Overall Response (OR) = CR + PR~Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)~Stable disease (SD) = Small changes that do not meet any of the above criteria" (NCT01437449)
Timeframe: 24 months

Interventionmonths (Median)
Cisplatin + Docetaxel + Cetuximab4.8

[back to top]

Overall Response Rate (ORR)

"Clinical response for each participant will be assessed after 8 weeks of treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Overall response rate (ORR) was assessed as the sum of the number of participants that experience a complete response (CR) or partial response (PR). The outcome is defined and reported as the number of subjects that responded, a number without dispersion. Other response statuses are included. RECIST v1.1 criteria is defined as follows.~Complete Response (CR) = Disappearance of all target lesions~Partial Response (PR) = ≥ 30% decrease in the sum of the longest diameter of target lesions~Overall Response (OR) = CR + PR~Progressive disease (PD) = 20% increase in the sum of the longest diameter of target lesions, and/or the appearance of one or more new lesion(s)~Stable disease (SD) = Small changes that do not meet any of the above criteria" (NCT01437449)
Timeframe: 8 weeks

Interventionparticipants (Number)
Complete Response (CR)Partial Response (PR)Overall Response (OR)Stable disease (SD)Progressive disease (PD)
Cisplatin + Docetaxel + Cetuximab1141556

[back to top]

Duration of Overall Response (DOR)

DOR was defined as the time from first objective status assessment of CR or PR to the first time of progression or death as a result of any cause. Response was defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. (NCT01439568)
Timeframe: Date of Response to Date of Progressive Disease (Up To 59 Months)

InterventionMonths (Median)
LY2510924 + Carboplatin + Etoposide4.83
Carboplatin + Etoposide4.67

[back to top]

Progression Free Survival (PFS)

PFS is defined as the time from the date of randomization to the first date of objectively determined progressive disease (PD) or death from any cause. For participants who are still alive at the time of analysis and without evidence of tumor progression, PFS will be censored at the date of the most recent objective progression-free observation. For participants who receive subsequent anticancer therapy (except PCI) prior to objective disease progression or death, PFS will be censored at the date of the last objective progression-free observation prior to the date of subsequent therapy. (NCT01439568)
Timeframe: Randomization to Measured Progressive Disease or Date of Death from Any Cause (Up To 59 Months)

InterventionMonths (Median)
LY2510924 + Carboplatin + Etoposide5.88
Carboplatin + Etoposide5.85

[back to top]

Overall Survival (OS)

Overall survival (OS) is defined as the time from the randomization to the date of death from any cause. For participants who are still alive as of the data cutoff date, OS time will be censored on the date of the participant's last contact (last contact for participants in postdiscontinuation is last known alive date in mortality status). (NCT01439568)
Timeframe: Randomization to Date of Death from Any Cause (Up To 59 Months)

InterventionMonths (Median)
LY2510924 + Carboplatin + Etoposide9.72
Carboplatin + Etoposide11.14

[back to top]

Number of Participants Achieving Complete Response (CR) or Partial Response (PR) (Overall Response Rate[ORR])

ORR is defined as the number of participants with a best response of CR and PR defined using Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) criteria. CR is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Tumor marker results must have normalized. PR is defined as at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.The appearance of one or more new lesions is also considered progression. (NCT01439568)
Timeframe: Baseline to Date of Tumor Response or Measured Progressive Disease or Date of Death from any Cause (Up to 59 Months)

InterventionParticipants (Count of Participants)
LY2510924 + Carboplatin + Etoposide35
Carboplatin + Etoposide34

[back to top]

Pathologic Response Rate

The percentage of patients with a major pathologic response (NCT01443078)
Timeframe: 2 years

Interventionpercentage of patients (Number)
All Patients17

[back to top]

PERCIST Partial Metabolic Response

"The primary endpoint was partial metabolic response after 2 cycles of switch therapy as assessed by PERCIST (SUVmax decrease ≥30% using the pre-switch scan as new baseline)." (NCT01443078)
Timeframe: 2 years

Interventionparticipants (Number)
All Patients6

[back to top]

Pharmacokinetics (AUClast)

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the AUClast. Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg) and per study part (Part 1 or Part 2). (NCT01447225)
Timeframe: Collections taken at Cycle 1, Week 1 for all patients at the start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion

Interventionhr* ug/mL (Geometric Mean)
MM-121 + Gemcitabine: 20/12 mg/kg39666.4
MM-121 + Carboplatin: 20/12 mg/kg49749.6
MM-121 + Pemetrexed: 20/12 mg/kg59984.1
MM-121 + Cisplatin: 20/12 mg/kg51995.1
MM-121 + Gemcitabine: 40/20 mg/kg72132.1
MM-121 + Carboplatin: 40/20 mg/kg100309.9
MM-121 + Pemetrexed: 40/20 mg/kg92732.9
MM-121 + Cisplatin: 40/20 mg/kg98142.6

[back to top]

Pharmacokinetics

Pharmacokinetic (PK) evaluation was performed on plasma samples obtained weekly for the first cycle of the study and then on day 1 of each additional cycle to assess pre-treatment trough concentrations of MM-121. Non-compartmental analysis (NCA) was performed to calculate standard PK parameters, including the maximum observed concentration (Cmax). Serum levels of MM-121 were measured at a central lab using an enzyme-linked immunosorbent assay (ELISA). Data is presented per dose level of MM-121 (12 mg/kg, 20 mg/kg, or 40/20 mg/kg). (NCT01447225)
Timeframe: Collections taken at Cycle 1, Week 1 for all patients at start of the infusion (pretreatment), at the end of the infusion, and at 2, 4, 24 and 48 hours after the start of the MM-121 infusion

Interventionug/mL (Geometric Mean)
MM-121 + Gemcitabine: 20/12 mg/kg560
MM-121 + Carboplatin: 20/12 mg/kg554.8
MM-121 + Pemetrexed: 20/12 mg/kg900.7
MM-121 + Cisplatin: 20/12 mg/kg677.1
MM-121 + Gemcitabine: 40/20 mg/kg1033.4
MM-121 + Carboplatin: 40/20 mg/kg1107.2
MM-121 + Pemetrexed: 40/20 mg/kg1100.8
MM-121 + Cisplatin: 40/20 mg/kg1087.9

[back to top]

To Characterize Dose-limiting Toxicities (DLTs) Associated With the Combination of MM-121 With Anticancer Therapies

To establish the safety of escalating doses of MM-121 administered in combination with multiple anti-cancer therapies in order to determine the recommended phase 2 dose. Dose-escalation conducted using standard 3+3 model to determine maximum tolerated dose. Reports of Dose-Limiting Toxicities (DLTs) were assessed to determine the MTD to be used for the expansion cohort. DLTs were not measured in the Expansion Cohort. (NCT01447225)
Timeframe: From date of first dose to 30 days after termination, the longest 88.1 weeks

Interventionparticipants reporting DLTs (Number)
MM-121 Plus Gemcitabine: Cohort 10
MM-121 Plus Gemcitabine: Cohort 21
MM-121 Plus Carboplatin: Cohort 11
MM-121 Plus Carboplatin: Cohort 20
MM-121 Plus Carboplatin: Cohort 30
MM-121 Plus Pemetrexed: Cohort 10
MM-121 Plus Pemetrexed: Cohort 21
MM-121 Plus Cabazitaxel: Cohort 10
MM-121 Plus Cabazitaxel: Cohort 20
MM-121 Plus Cabazitaxel: Cohort 30

[back to top]

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: MM-121 Doses

"Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.~Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8 Pemetrexed doses tested: 500 mg/m2 Day 1 Carboplatin doses tested: 5 or 6 AUC Day 1 Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3" (NCT01447225)
Timeframe: From date of first dose to 30 days after termination, the longest 88.1 weeks

,,,
Interventionmg/kg (Number)
one-time loading dosemaintenance dose
MM-121 Plus Cabazitaxel4020
MM-121 Plus Carboplatin4020
MM-121 Plus Gemcitabine4020
MM-121 Plus Pemetrexed4020

[back to top]

Immunogenicity

Samples were collected to determine the presence of an immunologic reaction to MM-121 (i.e. human anti-human antibodies). (NCT01447225)
Timeframe: Samples were collected for all patients pre-dose on all cycles for duration of treatment, the longest of which was 88.1 weeks, and a collection was made post-infusion in any case of infusion reaction

Intervention (Number)
MM-121 Plus Gemcitabine: Cohort 1NA
MM-121 Plus Gemcitabine: Cohort 2NA
MM-121 Plus Carboplatin: Cohort 1NA
MM-121 Plus Carboplatin: Cohort 2NA
MM-121 Plus Carboplatin: Cohort 3NA
MM-121 Plus Pemetrexed: Cohort 1NA
MM-121 Plus Pemetrexed: Cohort 2NA
MM-121 Plus Cabazitaxel: Cohort 1NA
MM-121 Plus Cabazitaxel: Cohort 2NA
MM-121 Plus Cabazitaxel: Cohort 3NA

[back to top]

Objective Response Rate

To determine the number of patients reporting an objective response using RECIST v 1.1 where a Partial Response (PR) is defined as >20% decrease in tumor burden from baseline and a Complete Response (CR) is defined as complete disappearance from tumor burden from baseline. Objective Response is presented as the total # patients with PR or CR. (NCT01447225)
Timeframe: patients were assessed for response during their time on study, the longest of which was 88.1 weeks

Interventionparticipants with objective response (Number)
MM-121 Plus Gemcitabine: Cohort 10
MM-121 Plus Gemcitabine: Cohort 22
MM-121 Plus Carboplatin: Cohort 10
MM-121 Plus Carboplatin: Cohort 20
MM-121 Plus Carboplatin: Cohort 30
MM-121 Plus Pemetrexed: Cohort 10
MM-121 Plus Pemetrexed: Cohort 21
MM-121 Plus Cabazitaxel: Cohort 11
MM-121 Plus Cabazitaxel: Cohort 22
MM-121 Plus Cabazitaxel: Cohort 31

[back to top]

To Evaluate the Safety and Tolerability of Escalating Doses of the MM-121 Anticancer Therapies

Safety and tolerability data presented in detail in the adverse events and serious adverse events section of the results posting (NCT01447225)
Timeframe: From date of first dose to 30 days after termination, the longest 88.1 weeks

Interventionparticipants reporting adverse events (Number)
MM-121 Plus Gemcitabine: Cohort 13
MM-121 Plus Gemcitabine: Cohort 28
MM-121 Plus Carboplatin: Cohort 15
MM-121 Plus Carboplatin: Cohort 23
MM-121 Plus Carboplatin: Cohort 33
MM-121 Plus Pemetrexed: Cohort 13
MM-121 Plus Pemetrexed: Cohort 27
MM-121 Plus Cabazitaxel: Cohort 14
MM-121 Plus Cabazitaxel: Cohort 23
MM-121 Plus Cabazitaxel: Cohort 34

[back to top]

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Pemetrexed

"Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.~Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Pemetrexed doses tested: 500 mg/m2 Day 1" (NCT01447225)
Timeframe: From date of first dose to 30 days after termination, the longest 88.1 weeks

Interventionmg/m2 (Number)
MM-121 + Pemetrexed500

[back to top]

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Cabazitaxel

"Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.~Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Cabazitaxel doses tested: 20 or 25 mg/m2 Day 1 of 3" (NCT01447225)
Timeframe: From date of first dose to 30 days after termination, the longest 88.1 weeks

Interventionmg/m2 (Number)
MM-121 + Cabazitaxel25

[back to top]

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Carboplatin

"Maximum Tolerated Dose reported in Target AUC, as calculated by the Calvert Formula~Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.~Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Carboplatin doses tested: 5 or 6 AUC Day 1" (NCT01447225)
Timeframe: From date of first dose to 30 days after termination, the longest 88.1 weeks

Interventiontarget AUC (mg*min/mL) (Number)
MM-121 + Carboplatin5

[back to top]

To Determine the Maximum Tolerated Dose (MTD) of MM-121 in Combination With Anticancer Therapies: Gemcitabine

"Using a 3+3 dose escalation model, the maximum tolerated dose of each therapy combination was determined by assessing dose-limiting toxicities in each cohort. If 3 patients were treated and passed the observation window, escalation to the next cohort was initiated. If a DLT was reported, 3-4 additional patients were enrolled and observed. If a DLT was observed in expanded cohort, this dose was considered to be the maximum tolerated dose. The maximum tolerated dose was defined at the cohort in which two dose-limiting toxicities were observed, or as the highest target dose tested in the absence of DLTs. The determined MTD was considered the Recommended Phase 2 Dose.~Dose Levels (3 week cycles) MM-121 doses tested: 20 mg/kg IV one-time loading dose then 12 mg/kg IV QW (20/12 mg/kg); 40/20 mg/kg Gemcitabine doses tested: 1000 mg/m2 Day 1 and 8" (NCT01447225)
Timeframe: From date of first dose to 30 days after termination, the longest 88.1 weeks

Interventionmg/m2 (Number)
MM-121 + Gemcitabine1000

[back to top]

Progression Free Survival (PFS) Time in Participants Who Have Received at Least One Dose of Blinded Study Therapy

Progression-Free Survival was defined as the time from the date of randomization to the date of progression per modified World Health Organization (mWHO) criteria or death, whichever occured first. A participant who died without reported progression per mWHO criteria was considered progressed on the date of death. For those participants who remained alive and did not progress, PFS was censored on the date of last evaluable tumor assessment. For those participants who remained alive and had no recorded post-baseline tumor assessment, PFS was censored on the day of randomization. (NCT01450761)
Timeframe: From randomization until disease progression, up to March 2015, approximately 38 months

Interventionmonths (Median)
Ipilimumab and Platinum/Etoposide4.63
Placebo and Platinum/Etoposide4.44

[back to top]

Overall Survival (OS) in Participants Who Received at Least One Dose of Blinded Study Therapy

Overall Survival was defined as the time from the date of randomization until the date of death from any cause. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. (NCT01450761)
Timeframe: Randomization until date of death, up to March 2015, approximately 38 months

Interventionmonths (Median)
Ipilimumab and Platinum/Etoposide10.97
Placebo and Platinum/Etoposide10.94

[back to top]

Overall Survival in All Randomized Participants

Overall Survival was defined as the time from the date of randomization until the date of death from any cause. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. (NCT01450761)
Timeframe: From randomization until date of death, up to March 2015, approximately 38 months

Interventionmonths (Median)
Ipilimumab and Platinum/Etoposide10.22
Placebo and Platinum/Etoposide9.95

[back to top]

Number of Participants With Abnormalities in Selected Thyroid Clinical Laboratory Tests

"The number of subjects with selected thyroid laboratory abnormalities is reported. FT3 and FT4 test abnormalities were considered for a 2-week window after the abnormal TSH test date.~TSH= thyroid-stimulating hormone; FT3= Free T3; FT4= Free T4; LLN= lower limit of normal; ULN= upper limit of normal" (NCT01454102)
Timeframe: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)

,,,,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
TSH > ULNTSH > ULN WITH TSH <= ULN AT BASELINETSH > ULN WITH >=1 FT3/FT4 TEST VALUE < LLNTSH > ULN WITH ALL FT3/FT4 TEST VALUES >= LLNTSH > ULN WITH FT3/FT4 TEST MISSINGTSH < LLNTSH < LLN WITH TSH >= LLN AT BASELINETSH < LLN WITH >=1 FT3/FT4 TEST VALUE > ULNTSH < LLN WITH ALL FT3/FT4 TEST VALUES <= ULNTSH < LLN WITH FT3/FT4 TEST MISSING
Arm A: Nivolumab + Gemcitabine + Cisplatin2100221101
Arm B: Nivolumab + Pemetrexed + Cisplatin3212073133
Arm C10: Nivolumab + Paclitaxel + Carboplatin1101051014
Arm C5: Nivolumab + Paclitaxel + Carboplatin5420375205
Arm D: Nivolumab + Bevacizumab Maintenance8410721011
Arm E: Nivolumab + Erlotinib12870577403
Arm F: Nivolumab2113341499414
Arm GH: Nivolumab + Ipilimumab10105141212633
Arm IJ: Nivolumab + Ipilimumab7652099513
Arm K: Nivolumab in Squamous Histology Subjects (NSCLC)5532033210
Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC)5302310100
Arm M: Nivolumab2100264105
Arm N: Nivolumab + Ipilimumab10761399621
Arm O: Nivolumab + Ipilimumab129714109721
Arm P: Nivolumab + Ipilimumab11550666114
Arm Q: Nivolumab + Ipilimumab11842599117

[back to top]

Progression-Free Survival Rate (PFSR) at Week 24

"Progression-Free Survival (PFS) was defined as the time from the date of first dose of study medication to the date of first disease progression or death, if death occurred within 100 days of the final dose of study drug. Among participants without previous RECIST-defined progression, participants who died beyond 100 days and those who remained alive were censored at the last tumor assessment date (before subsequent therapy).~PFSR at week 24 was defined as the proportion of subjects remaining progression free and surviving at 24 weeks. The proportion was calculated by the product-limit method (Kaplan-Meier estimate), which takes into account censored data, and expressed as a percentage." (NCT01454102)
Timeframe: 24 weeks

InterventionPercentage of participants (Number)
Arm A: Nivolumab + Gemcitabine + Cisplatin50.5
Arm B: Nivolumab + Pemetrexed + Cisplatin68.4
Arm C10: Nivolumab + Paclitaxel + Carboplatin34.3
Arm D: Nivolumab + Bevacizumab Maintenance58.3
Arm E: Nivolumab + Erlotinib50.6
Arm F: Nivolumab39.7
Arm GH: Nivolumab + Ipilimumab42.8
Arm IJ: Nivolumab + Ipilimumab37.3
Arm K: Nivolumab in Squamous Histology Subjects (NSCLC)50.0
Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC)20.5
Arm M: Nivolumab8.3
Arm N: Nivolumab + Ipilimumab49.1
Arm O: Nivolumab + Ipilimumab48.0
Arm P: Nivolumab + Ipilimumab72.4
Arm Q: Nivolumab + Ipilimumab39.5
Arm C5: Nivolumab + Paclitaxel + Carboplatin59.3

[back to top]

Number of Participants With Abnormalities in Selected Hepatic Clinical Laboratory Tests

"The number of subjects with selected hepatic laboratory abnormalities is reported.~AST= aspartate aminotransferase; ALT= alanine aminotransferase; ULN= upper limit of normal." (NCT01454102)
Timeframe: From first dose to 30 days following last dose of study drug (assessed up to July 2016, approximately 55 months)

,,,,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
ALT OR AST > 3XULNALT OR AST > 5XULNALT OR AST > 10XULNALT OR AST > 20XULNTOTAL BILIRUBIN > 2XULNAST or ALT>3XULN with Bilirubin>2XULN within 1 dayAST or ALT>3XULN with Bilirubin>2XULN within 30day
Arm A: Nivolumab + Gemcitabine + Cisplatin0000000
Arm B: Nivolumab + Pemetrexed + Cisplatin0000000
Arm C10: Nivolumab + Paclitaxel + Carboplatin2000000
Arm C5: Nivolumab + Paclitaxel + Carboplatin2000000
Arm D: Nivolumab + Bevacizumab Maintenance1000000
Arm E: Nivolumab + Erlotinib4210111
Arm F: Nivolumab2200111
Arm GH: Nivolumab + Ipilimumab6421000
Arm IJ: Nivolumab + Ipilimumab0000000
Arm K: Nivolumab in Squamous Histology Subjects (NSCLC)0000000
Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC)0000000
Arm M: Nivolumab0000000
Arm N: Nivolumab + Ipilimumab1111000
Arm O: Nivolumab + Ipilimumab2100000
Arm P: Nivolumab + Ipilimumab1000000
Arm Q: Nivolumab + Ipilimumab0000000

[back to top]

Objective Response Rate (ORR)

ORR was defined as the percentage of all treated participants who achieved a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria as per investigator assessment. This proportion was multiplied by 100 and expressed as a percentage. BOR was defined as the best response designation recorded between the date of randomization and the date of progression, or the date of subsequent anticancer therapy, whichever occurred first. CR or PR determinations included in the BOR assessment were confirmed by a second scan at least 4 weeks after the criteria for responses were first met. For participants without progression or subsequent therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial progression. (NCT01454102)
Timeframe: From first dose until date of progression or subsequent anti-cancer therapy (assessed up to July 2016, approximately 55 months)

InterventionPercentage of participants (Number)
Arm A: Nivolumab + Gemcitabine + Cisplatin41.7
Arm B: Nivolumab + Pemetrexed + Cisplatin46.7
Arm C10: Nivolumab + Paclitaxel + Carboplatin46.7
Arm D: Nivolumab + Bevacizumab Maintenance16.7
Arm E: Nivolumab + Erlotinib19.0
Arm F: Nivolumab23.1
Arm GH: Nivolumab + Ipilimumab20.8
Arm IJ: Nivolumab + Ipilimumab24.0
Arm K: Nivolumab in Squamous Histology Subjects (NSCLC)0
Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC)15.4
Arm M: Nivolumab8.3
Arm N: Nivolumab + Ipilimumab22.6
Arm O: Nivolumab + Ipilimumab32.5
Arm P: Nivolumab + Ipilimumab47.4
Arm Q: Nivolumab + Ipilimumab38.5
Arm C5: Nivolumab + Paclitaxel + Carboplatin50.0

[back to top]

Number of Participants Who Experienced Selected Adverse Events

"The number of participants who experienced an AE of interest due to any cause is presented. Endocrine, Gastrointestinal, Hepatic, Pulmonary, Renal, Skin, and~Hypersensitivity/Infusion select AEs were identified that are potentially associated with the use of nivolumab, based on the following 4 guiding principles:~AEs that may differ in type, frequency, or severity from AEs caused by non-immunotherapies~AEs that may require immunosuppression (eg, corticosteroids) as part of their management~AEs whose early recognition and management may mitigate severe toxicity~AEs for which multiple event terms may be used to describe a single type of AE, thereby necessitating the pooling of terms for full characterization." (NCT01454102)
Timeframe: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)

,,,,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
EndorcrineGastrointestinalHepaticPulmonaryRenalSkinHypersensitivity/Infusion Reactions
Arm A: Nivolumab + Gemcitabine + Cisplatin3402131
Arm B: Nivolumab + Pemetrexed + Cisplatin2622696
Arm C10: Nivolumab + Paclitaxel + Carboplatin0810177
Arm C5: Nivolumab + Paclitaxel + Carboplatin1601471
Arm D: Nivolumab + Bevacizumab Maintenance2202151
Arm E: Nivolumab + Erlotinib410412162
Arm F: Nivolumab816530274
Arm GH: Nivolumab + Ipilimumab815732151
Arm IJ: Nivolumab + Ipilimumab612220143
Arm K: Nivolumab in Squamous Histology Subjects (NSCLC)3521342
Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC)2102020
Arm M: Nivolumab0100020
Arm N: Nivolumab + Ipilimumab412432201
Arm O: Nivolumab + Ipilimumab15131332201
Arm P: Nivolumab + Ipilimumab811156213
Arm Q: Nivolumab + Ipilimumab1213234201

[back to top]

Number of Participants Who Experienced Serious Adverse Events (SAE), Adverse Events (AE) Leading to Discontinuation, or Death

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4= Potentially Life-threatening or disabling. (NCT01454102)
Timeframe: From first dose to 30 days after the last dose of study drug (assessed up to July 2016, approximately 55 months)

,,,,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
SAEsAEs leading to discontinuationDeath
Arm A: Nivolumab + Gemcitabine + Cisplatin420
Arm B: Nivolumab + Pemetrexed + Cisplatin1050
Arm C10: Nivolumab + Paclitaxel + Carboplatin810
Arm C5: Nivolumab + Paclitaxel + Carboplatin920
Arm D: Nivolumab + Bevacizumab Maintenance330
Arm E: Nivolumab + Erlotinib1130
Arm F: Nivolumab2392
Arm GH: Nivolumab + Ipilimumab18112
Arm IJ: Nivolumab + Ipilimumab17133
Arm K: Nivolumab in Squamous Histology Subjects (NSCLC)330
Arm L: Nivolumab in Non-squamous Histology Subjects (NSCLC)441
Arm M: Nivolumab411
Arm N: Nivolumab + Ipilimumab1231
Arm O: Nivolumab + Ipilimumab2141
Arm P: Nivolumab + Ipilimumab25104
Arm Q: Nivolumab + Ipilimumab2582

[back to top]

Phase I: Overall Frequency of Response

"To determine the overall frequency of response--overall response will include all subjects with complete response (CR) and partial response (PR). Based on the revised response criteria for malignant lymphoma [Cheson 2007]~CR= complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy PR= >/= 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no increase in size of other nodes, liver or spleen;" (NCT01458366)
Timeframe: CT and PET scans after Cycle 2 (approximately 25 days) and 3-8 weeks post-treatment

InterventionParticipants (Count of Participants)
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)7

[back to top]

Total Overall Survival for Transplant vs Non-transplant

1 and 2 year overall survival for those who received Stem Cell Transplant (SCT) versus those who did not receive SCT (NCT01458366)
Timeframe: At 1 and 2 years after completion of treatment; year 2 reported

Interventionmonths (Median)
Did not receive transplantReceived transplant
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)7.427.3

[back to top]

Phase I: Maximum-Tolerated Dose of Bendamustine in Combination With Ofatumumab, Carboplatin and Etoposide (BOCE)

To determine the maximum-tolerated dose of bendamustine in combination with ofatumumab, carboplatin and etoposide for patients with refractory or relapsed aggressive B cell lymphomas. Toxicity levels will be assessed after every cycle until a dose-limiting toxicity (DLT) is found. Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria (CTCAE version 4.0). DLT will be defined as any grade 4 infection, or grade >/= 3 non-hematologic toxicity that persists for 7 days or more. (NCT01458366)
Timeframe: Baseline through 50 days

Interventionmg/m^2 (Number)
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)120

[back to top]

Overall Progression-Free Survival

To determine 1 and 2 year progression-free survival [Cheson 2007] CR= complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy PR= >/= 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no increase in size of other nodes, liver or spleen; (NCT01458366)
Timeframe: At 1 and 2 years after completion of treatment; year 2 reported

Interventionmonths (Median)
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)5.1

[back to top]

Overall Frequency of Response With Combination of Bendamustine, Ofatumumab, Carboplatin, and Etoposide at Maximum Tolerated Dose (MTD)

To determine the overall frequency of response with combination bendamustine, ofatumumab, carboplatin, and etoposide for refractory or relapsed aggressive B-cell lymphomas. Overall response is determined as cumulative Complete Response (CR) and Partial Response (PR). (NCT01458366)
Timeframe: At 25 days and 3-8 weeks post-treatment

InterventionParticipants (Count of Participants)
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)20

[back to top]

Overall Complete Response (CR) and Partial Response (PR) Rate

"Based on the revised response criteria for malignant lymphoma [Cheson 2007]~CR= complete disappearance of all detectable clinical evidence of disease and disease related symptoms if present before therapy PR= >/= 50% decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses; no increase in size of other nodes, liver or spleen;" (NCT01458366)
Timeframe: CT and PET scans after Cycle 2 (approximately 25 days) and 3-8 weeks post-treatment

InterventionParticipants (Count of Participants)
Phase 272275434Phase 172275434
Complete ResponsePartial ResponseNo response
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)12
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)4
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)8
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)5
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)3

[back to top]

Overall Proportion of Patients Who Are Able to Undergo Stem Cell Transplant (SCT)

To determine the proportion of patients who are able to undergo stem cell transplant among transplant-eligible patients. Patients can receive SCT after Cycle 2. (NCT01458366)
Timeframe: At 2 years after completion of treatment

InterventionParticipants (Count of Participants)
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)12

[back to top]

Overall Safety and Tolerability of the Combination of Bendamustine, Ofatumumab, Carboplatin, and Etoposide

"To define safety and tolerability of the combination of ofatumumab, bendamustine, carboplatin and etoposide as measured by the number of dose modifications made to Bendamustine..~Determined through dose modifications for bendamustine according to patient's toxicity levels:~Initial 120 mg/m2 dose decreased to 90 mg/m2~Initial 90 mg/m2 dose decreased to 70 mg/m2~Initial 70 mg/m2 dose decreased to 50 mg/m2~Initial 50 mg/m2 dose decreased to Withdrawn from study" (NCT01458366)
Timeframe: After each cycle (after approximately 3 days, 25 days, and 50 days)

Interventiondose modifications (Number)
Bendamustine, Ofatumumab, Carboplatin, and Etoposide (BOCE)0

[back to top]

Progression Free Survival (PFS) of Cabazitaxel-carboplatin Versus Cabazitaxel in the Phase II Portion of Study

PFS is the time from the first dose until progression of disease or death, whichever comes first. PFS times will be estimated using the Kaplan-Meier method. (NCT01505868)
Timeframe: From the first dose until progression of disease or death, whichever comes first, up to 5 years

Interventionmonths (Median)
Phase II Cabazitaxel4.5
Phase II Cabazitaxel + Carboplatin7.3

[back to top]

Prostate Specific Antigen (PSA) Response Rate

Percentage of participants with a greater than 50% decrease in measurable values of PSA during treatment from their baseline PSA. (NCT01505868)
Timeframe: 5 years

Interventionpercentage of participants (Number)
Phase II Cabazitaxel40.9
Phase II Cabazitaxel + Carboplatin61.7

[back to top]

Overall Survival (OS)

Time from date of treatment start until date of death due to any cause or last follow up. (NCT01505868)
Timeframe: Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years

Interventionmonths (Median)
Phase II Cabazitaxel17.3
Phase II Cabazitaxel + Carboplatin18.5

[back to top]

Aggressive Variant Prostate Carcinoma-Metastatic (ACPC-MS) Phenotypes Correlated to Response

PFS and OS were reported for participants with and without AVPC-MS in the cabazitaxel vs cabazitaxel + carboplatin treatment groups (NCT01505868)
Timeframe: 5 years

,
Interventionmonths (Median)
Cabazitaxel PFSCabazitaxel + carboplatin PFSCabazitaxel OSCabazitaxel + carboplatin OS
AVPC-MS Negative6.36.521.721.5
AVPC-MS Postive1.77.58.520.2

[back to top]

Phase II Most Common Grade 3-5 Adverse Events

Grade 3: Serious reaction which requires medical treatment Grade 4: Life threatening. Grade 5 Death. (NCT01505868)
Timeframe: Time from date of treatment start until date of death due to any cause or last follow up, up to 5 years

,
InterventionParticipants (Count of Participants)
FatiqueAnemiaNeutropeniaThrombocytopenia
Phase II Cabazitaxel9441
Phase II Cabazitaxel + Carboplatin20231614

[back to top]

Bone-Specific Alkaline Phosphatase Response

Percentage of participants with a greater than 50% decrease in measurable values of bone-specific alkaline phosphatase during treatment from their baseline values (NCT01505868)
Timeframe: 5 years

Interventionpercentage of participants (Number)
Phase II Cabazitaxel29.4
Phase II Cabazitaxel + Carboplatin62

[back to top]

Maximum Tolerated Dosage (MTD) of Cabazitaxel-carboplatin in the Phase I Portion of Study

The MTD was defined as the highest dose cohort studied in which one of six or fewer patients experienced a dose-limiting toxicity. (NCT01505868)
Timeframe: 6 months

Interventionmg/m^2 (Number)
Phase I Cabazitaxel + Carboplatin25

[back to top]

Urine N-Telopeptides Response

Percentage of participants with a greater than 50% decrease in measurable values of urine n-telopeptides during treatment from their baseline values. (NCT01505868)
Timeframe: 5 years

Interventionpercentage of participants (Number)
Phase II Cabazitaxel55
Phase II Cabazitaxel + Carboplatin62.5

[back to top]

Overall Survival (OS)

Time to death for a given participant was defined as the number of months from the day the participant is randomized to the date of the participant's death. All events of death were included, regardless of whether the event occurs while the participant was still taking study drug, or after the participant discontinued study drug. If a participant had not died, then the data will be censored at the date when the participant was last known to be alive. (NCT01506609)
Timeframe: From Cycle 1 Day 1 until participant's death or 3 years post discontinuation (data cutoff date: 04 March 2016); maximum duration of follow up for OS was 72 months.

Interventionmonths (Median)
Group 2 Placebo + Carboplatin/Paclitaxel25.4
Group 2 Veliparib + Carboplatin/Paclitaxel28.3
Group 2 Veliparib + TMZ19.1

[back to top]

Progression-Free Survival (PFS)

PFS is defined as the number of months from the date the participant was randomized to the date of radiographic progression as determined by the central imaging center, or to the date of all cause deaths within 63 days of last tumor assessment if disease progression was not reached. (NCT01506609)
Timeframe: Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for PFS was 34 months.

Interventionmonths (Median)
Group 2 Placebo + Carboplatin/Paclitaxel12.3
Group 2 Veliparib + Carboplatin/Paclitaxel14.1
Group 2 Veliparib + TMZ7.4

[back to top]

Clinical Benefit Rate (CBR) at Week 18

"CBR: percentage of participants who were progression-free at 18 weeks, defined as complete response (CR), partial response (PR), stable disease (SD) or non-CR/non-disease progression (PD) per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1.~CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 0 mm. PR: >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (SOD). PD: >= 20% increase in the SOD of target lesions, taking as reference the smallest SOD recorded since the treatment started (baseline or after) or the appearance of >=1 new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SOD since the treatment started (baseline or after)." (NCT01506609)
Timeframe: Week 18

Interventionpercentage of participants (Number)
Group 2 Placebo + Carboplatin/Paclitaxel87.0
Group 2 Veliparib + Carboplatin/Paclitaxel90.7
Group 2 Veliparib + TMZ73.0

[back to top]

Change From Baseline at Week 18 in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Subscale Score

EORTC QLQ-CIPN20 sensory subscale score was calculated following the standard scoring algorithm, transformed to a 0 (low quality of life) to 100 (best quality of life) scale. A positive change from baseline indicates improvement. (NCT01506609)
Timeframe: Baseline, Week 18

Interventionscore on a scale (Mean)
Group 2 Placebo + Carboplatin/Paclitaxel13.94
Group 2 Veliparib + Carboplatin/Paclitaxel11.24

[back to top]

Objective Response Rate (ORR)

The objective response rate, defined as percentage of participants with a confirmed CR or PR based on RECIST 1.1 criteria. CR: The disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 0 mm. PR: >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline SODs. (NCT01506609)
Timeframe: Radiographic evaluation every 9 weeks, clinical evaluation every cycle (data cutoff date: 04 March 2016); maximum duration of follow up for ORR was 34 months.

Interventionpercentage of participants (Number)
Group 2 Placebo + Carboplatin/Paclitaxel61.3
Group 2 Veliparib + Carboplatin/Paclitaxel77.8
Group 2 Veliparib + TMZ28.6

[back to top]

Overall Survival

Estimated by the Kaplan-Meier method. Three-year point estimate and 95% confidence interval based on the Greenwood variance, with log-log transformation, will be provided. The corresponding median survival times (with 90% confidence limits) will be determined. Patients' survival times will be measured from the initial date of treatment to the recorded date of death, or most recent follow-up at the end-of-study date. (NCT01525966)
Timeframe: Up to three years post-commencement of chemotherapy.

Interventionpercentage of surviving patients: 3-yr (Number)
Treatment (Carboplatin and Nab-paclitaxel)90.2

[back to top]

Progression-free Survival

Estimated by the Kaplan-Meier method. Three-year point estimate and 95% confidence interval based on the Greenwood variance, with log-log transformation, will be provided. Patients' survival times will be measured from the initial date of treatment to the recorded date of progression or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT01525966)
Timeframe: Up to three years.

Interventionpercentage of pts (Number)
Treatment (Carboplatin and Nab-paclitaxel)87.3

[back to top]

Overall Survival

Overall Survival will be measured at the end of study. number of surviving participants is reported. (NCT01542736)
Timeframe: up to 5 years

InterventionParticipants (Count of Participants)
Reduced Radiation With Concurrent Chemotherapy7

[back to top]

Event-free Survival

MRIs of the head and spine. Number of participants with event free survival at 60 months is reported. (NCT01542736)
Timeframe: Up to 60 months.

InterventionParticipants (Count of Participants)
Reduced Radiation With Concurrent Chemotherapy7

[back to top]

Intellectual Competence Measured by IQ Score: Month 24

Neuropsychological testing will be performed after radiation in completed. IQ score is reported. The Wechsler Intelligence Scale for Children, 5th edition (WISC-V) measures intellectual competence in Verbal Comprehension, Visual Spatial, Fluid Reasoning, Working Memory, and Processing Speed. The average score for the scale is fixed at 100, with a standard deviation of 15. Higher scores indicate higher levels of intellectual competence and a better outcome. (NCT01542736)
Timeframe: Month 24

Interventionscore on a scale (Mean)
Reduced Radiation With Concurrent Chemotherapy96.83

[back to top]

Intellectual Competence Measured by IQ Score: Month 60

Neuropsychological testing will be performed after radiation in completed. IQ score is reported. The Wechsler Intelligence Scale for Children, 5th edition (WISC-V) measures intellectual competence in Verbal Comprehension, Visual Spatial, Fluid Reasoning, Working Memory, and Processing Speed. The average score for the scale is fixed at 100, with a standard deviation of 15. Higher scores indicate higher levels of intellectual competence and a better outcome. (NCT01542736)
Timeframe: Month 60

Interventionscore on a scale (Mean)
Reduced Radiation With Concurrent Chemotherapy79

[back to top]

Intellectual Competence Measured by IQ Score: Week 8

Neuropsychological testing will be performed after radiation in completed. The Wechsler Intelligence Scale for Children, 5th edition (WISC-V) measures intellectual competence in Verbal Comprehension, Visual Spatial, Fluid Reasoning, Working Memory, and Processing Speed. The average score for the scale is fixed at 100, with a standard deviation of 15. Higher scores indicate higher levels of intellectual competence and a better outcome. (NCT01542736)
Timeframe: Week 8

Interventionscore on a scale (Mean)
Reduced Radiation With Concurrent Chemotherapy102.4

[back to top]

Response to Therapy

Percentage of participants with complete or partial response to combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (NCT01578551)
Timeframe: 2 years

Interventionpercentage of participants (Number)
Arm A56
Arm B33

[back to top]

Overall Survial

Number of months alive after 1 year of the combination of metformin with standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma. (NCT01578551)
Timeframe: up to 2 years

Interventionmonths (Median)
Arm A15.9
Arm B13.9

[back to top]

Progression Free Survival (PFS)

Number of months without evidence of progression after 1 year of the combination of metformin and standard chemotherapy in patients with previously untreated advanced or metastatic pulmonary adenocarcinoma. (NCT01578551)
Timeframe: 1 year

Interventionmonths (Median)
Arm A9.6
Arm B6.7

[back to top]

3-year PFS Rate of Patients With Localized CNS Germinoma Who Were Treated With Reduced Dose Radiation Therapy

"Binomial estimate of the 3-year PFS rate defined as Yes for patients who were followed up per protocol and were progression free at 3-years, and No for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from initiation of treatment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study." (NCT01602666)
Timeframe: 3 years

Interventionpercentage of patients (Number)
Stratum 2 Localized Germinoma86.49

[back to top]

3-year Progression-free Survival (PFS) Rate of Patients With Nongerminomatous Germ Cell Tumor (NGGCT) Who Were Treated With Reduced Dose Whole Ventricular-field Irradiation

"Binomial estimate of the 3-year PFS rate defined as Yes for patients who were followed up per protocol and were progression free at 3-years, and No for those who either experienced a progression or were lost to follow-up/withdrew from the trial within 3 years from enrollment. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study." (NCT01602666)
Timeframe: 3 years

Interventionpercentage of patients (Number)
Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)83.33

[back to top]

Estimation of the OS Distribution of Patients With Localized Germinoma Patients and CSF Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL

Kaplan Meier estimate of the 3-year overall survival (OS) is provided for each group. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. (NCT01602666)
Timeframe: Up to 3 years

Interventionpercentage of patients (Number)
hCGbeta <= 50 mIU/mL98.38
50 mIU/mL < hCGbeta <= 100 mIU/mL100

[back to top]

Estimation of the Overall Survival (OS) Distribution of Patients With NGGCT Treated With IFR Assessed

Kaplan Meier estimate of the 3-year overall survival (OS) is provided. OS is the time interval measured from enrollment until death from any cause or until last follow-up for those who were alive at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. (NCT01602666)
Timeframe: Up to 3 years

Interventionpercentage of patients (Number)
Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)92.42

[back to top]

Estimation of the PFS Distribution of Patients With NGGCT Treated With Involved-field Radiation Therapy (IFR)

Kaplan Meier estimate of the 3-year PFS is provided. PFS is the time interval measured from enrollment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study. (NCT01602666)
Timeframe: Up to 3 years

Interventionpercentage of patients (Number)
Stratum 1 Localized Non-Germinomatous Germ Cell Tumors (NGGCT)87.88

[back to top]

Estimation of the PFS Distribution of Patients With Localized Germinoma Patients and Cerebrospinal Fluid (CSF) Serum hCGbeta of 50 mIU/mL or Less or CSF Serum hCGbeta Greater Than 50 mIU/mL and Less Than or Equal to 100 mIU/mL

Kaplan Meier estimate of the 3-year PFS rate is provided. PFS is the time interval measured from initiation of treatment until progression or death from any cause or until last follow-up for those who were event free at the time of analysis. Patients who were lost to follow-up or withdrew consent were censored in this analysis. Progression was determined by MRI using the COG Guidelines for Measurement of Tumor Size (>25% increase in 2D or >40% in 3D of the product of perpendicular diameters of the target lesion) as well as by tumor marker assessments which were mandatory for this study. (NCT01602666)
Timeframe: Up to 3 years

Interventionpercentage of patients (Number)
hCGbeta <= 50 mIU/mL93.26
50 mIU/mL < hCGbeta <= 100 mIU/mL80.00

[back to top]

Response Rates at the Primary Site

Evaluation of target lesions through tumor imaging (CT scan, MRI, and/or chest x-ray) at 3-5 weeks post induction chemotherapy. Overall response rate will be based on RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. (NCT01612351)
Timeframe: 11 weeks

InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable Disease
Non-Randomized Single-Arm15213

[back to top]

Voice and Swallowing Function- MD Anderson Dysphagia Inventory (MDADI)

The MD Anderson Dysphagia Inventory (MDADI) is a 20 item assessment designed to measure voice and swallowing function. Participants were asked 13 symptom questions and 6 interference items (walking, working) and asked id the 1- strongly agree to 5 strongly disagree. Scores were summed for a range of 20-100. The lower the score the worse the outcomes. (NCT01612351)
Timeframe: Pre-treatment up to 1 year post surgery

Interventionunits on a scale (Mean)
Pre-treatment83.90
Post-Induction86.26
1 Year Post Surgery81.90

[back to top]

Number of Patients Who Decreased in Risk Level Post Induction Chemotherapy.

Number of patients who no longer need radiation (have decreases in risk level post induction therapy). Estimations of Risk level pre-induction will be based on physical examination and imaging, post-induction risk level will be determined based on pathologic evaluation or surgical specimen. (NCT01612351)
Timeframe: 11 weeks

InterventionParticipants (Count of Participants)
Induction Chemotherapy Followed by Transoral Surgery29

[back to top]

Voice and Swallowing Function - Voice-Related Quality of Life Assessment (VRQOL)

The Voice-Related Quality of Life Tool is a 10 item list of possible voice-related problems. The participant answers 1-5 with 1 being none, not a problem to 5, problem is as bad as it can be. An algorithm is used to calculate the scores, so that sum scores range from 0 to 100, where 0 indicates poor V-RQOL and 100 indicates good V-RQOL (NCT01612351)
Timeframe: Pre-treatment up to 1 year post surgery

Interventionunits on a scale (Mean)
Pre-treatment93.42
Post-Induction92.00
1 Year Post Surgery91.85

[back to top]

Estimate the Pathologic Complete Response Rate at the Primary Site and in the Neck Following Induction Chemotherapy

Pathologic complete response (pCR) is the disappearance of all signs of cancer in tissue samples removed during surgery or biopsy (pT0). Also called pathologic complete remission. Pathologic Partial Response (pPR), is the presence of only non-invasive cancer in tissue samples (NCT01612351)
Timeframe: 11 weeks

InterventionParticipants (Count of Participants)
Pathologic complete response (pCR)Pathologic Partial Response (pPR)
Induction Chemotherapy Followed by Transoral Surgery1425

[back to top]

Overall Response Rate

Evaluation of target lesions through tumor imaging (CT scan, MRI, and/or chest x-ray) at 3-5 weeks post induction chemotherapy. Overall response rate will be based on RECIST criteria. Overall response rate (ORR) is defined as the number of patients who have a partial or complete response to therapy. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT01612351)
Timeframe: 11 weeks

InterventionParticipants (Count of Participants)
Induction Chemotherapy Followed by Transoral Surgery37

[back to top]

Feasibility of 3 Part Therapy

Percentage of patients successfully completing 3 part therapy will be used to assess the feasibility of 3 part therapy consisting of induction chemotherapy, surgery, and risk-adapted use of chemoradiation. (NCT01612351)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
completednot-completed
Induction Chemotherapy Followed by Transoral Surgery391

[back to top]

Number of Subjects Who Experience Grade 3/4 Adverse Events According to CTCAE 4.0

The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. (NCT01612351)
Timeframe: 18 weeks

InterventionParticipants (Count of Participants)
Alanine aminotransferase increasedAspartate Aminotransferase increasedChest pain- cardiacDiarrheaFatigueFebrile neutropeniaHyperglycemiaHyponatremiaHypotensionLymphocyte count decreasedNauseaNeutrophil count decreasedPalmar-plantar erythrodysesthesia syndromePeripheral sensory neuropathyRash acneiformSepsisWhite blood cell decreased
Induction Chemotherapy Followed by Transoral Surgery2115441111122124115

[back to top]

Response Rates at the Neck.

Evaluation of target lesions through tumor imaging (CT scan, MRI, and/or chest x-ray) at 3-5 weeks post induction chemotherapy. Overall response rate will be based on RECIST criteria. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for neck lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions. (NCT01612351)
Timeframe: 11 weeks

InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable Disease
Non-Randomized Single-Arm11153

[back to top]

Functional Assessment QOL

University of Michigan Head and Neck Quality of Life Instrument (HN-QOL) will be administered prior to treatment (i.e. pre-induction chemotherapy) and at 6 months, 12 months, and 24 months (+/- 4 months) after completion of chemo-RT or surgery-RT (or surgery-chemoRT, as indicated). Scale is 0-100 with high scores indicating a better outcome. EATING Domain is reported here as a functional assessment. (NCT01633541)
Timeframe: Up to 28 months post treatment

,
Interventionscore on a scale (Median)
EATING- Prior to treatmentEATING- 6 monthsEATING- 12 monthsEATING- 24 months
Active Comparator Arm91.783.383.395.8
Platinum/Docetaxal + AT-10183.37583.377.1

[back to top] [back to top] [back to top]

Percentage of Patients Experiencing Grade 3 or Higher Adverse Events.

Toxicities will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE), version 3. (NCT01633541)
Timeframe: Up to 3 years after end of treatment

Interventionpercentage of Patients (Number)
Platinum/Docetaxal + AT-10161
Active Comparator Arm44

[back to top]

Overall Response Rate (ORR)

ORR (Complete Response [CR] plus Partial Response [PR]) to induction chemotherapy with platinum and docetaxel plus AT-101 following one and/or two cycles in patients with advanced laryngeal cancer. (NCT01633541)
Timeframe: Up to approximately 60 days

InterventionParticipants (Count of Participants)
Platinum/Docetaxal + AT-10127

[back to top]

Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment

The primary clinical objective of this trial is to compare the larynx preservation rates in a treatment paradigm that uses induction chemotherapy plus AT-101 to select patients for either concurrent chemoradiation or surgery. Organ preservation rate, defined as alive and free from indication for laryngectomy three months post treatment, was chosen as the primary endpoint because it provides evidence to fully characterize clinically the effect of the treatment strategy (NCT01633541)
Timeframe: Up to 3 months after end of treatment

InterventionParticipants (Count of Participants)
Platinum/Docetaxal + AT-10127
Active Comparator Arm12

[back to top]

Progression-free Survival

Time from randomization to the time of first indication of local failure or metastases. Estimated non-parametrically using the Kaplan-Meier method. (NCT01633541)
Timeframe: Up to 3 years after randomization

Interventionpercentage of participants (Number)
Platinum/Docetaxal + AT-10155
Active Comparator Arm65

[back to top]

Objective Response Rate (ORR) - Percentage of Participants With Objective Response Based on IRR

Percentage of participants with objective response of complete response (CR) or partial response (PR) according to RECIST version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. (NCT01639001)
Timeframe: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (assessed up to 33 months)

InterventionPercentage of participants (Number)
Crizotinib87.5
Chemotherapy45.6

[back to top]

Change From Baseline in Functioning and Global Quality of Life (QOL) as Assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). The QLQ-C30 Global QOL, Physical Functioning, Role Functioning, Cognitive Functioning, Emotional Functioning, and Social Functioning each ranged from 0-100 with higher scores indicating a better level of functioning or better quality of life. (NCT01639001)
Timeframe: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）

,
InterventionUnits on a scale (Mean)
QLQ-C30 Global QoLQLQ-C30 Cognitive FunctioningQLQ-C30 Emotional FunctioningQLQ-C30 Physical FunctioningQLQ-C30 Role FunctioningQLQ-C30 Social Functioning
Chemotherapy-2.3619-4.80262.0557-2.9562-5.7570-4.7228
Crizotinib5.0891-1.18963.70773.77051.05380.8712

[back to top]

Agreement Between Central Laboratory ALK FISH and ALK IHC Test Results - Molecular Profiling Evaluable

Agreement between central laboratory anaplastic lymphoma kinase (ALK) fluorescence in situ hybridization (FISH) and ALK immunohistochemistry (IHC) test results is based on analysis of participants in the Molecular Profiling (MP) evaluable population that have an ALK IHC result and an ALK FISH result of either positive or negative only. This MP evaluable population included participants who screen failed, which their ALK test results were negative based on FISH test. Tumor tissue samples from these screen failure participants were consented and kept. These samples served as a part of negative sample set for evaluation of IHC test and/or polymerase chain reaction (PCR) to determine ALK fusion events. Participants with FISH results of uninformative and assay not performed and IHC results of valid IHC status not available were excluded from the analysis of agreement between central laboratory ALK FISH and ALK IHC test results. (NCT01639001)
Timeframe: During the screening (less than or equal to 28 days prior to dosing)

,
InterventionParticipants (Count of Participants)
Participants with Positive ALK IHC StatusParticipants with Negative ALK IHC Status
Participants With Negative ALK FISH Status31502
Participants With Positive ALK FISH Status21820

[back to top]

Time to Progression (TTP) Based on IRR

TTP was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression, as determined by IRR. If tumor progression data included more than 1 date, the first date was used. TTP (in months) was calculated as (first event date - randomization date +1)/30.44. (NCT01639001)
Timeframe: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)

InterventionMonths (Median)
Crizotinib12.0
Chemotherapy6.9

[back to top]

Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, or Cough Assessed Using Quality of Life Questionnaire Supplement Module for Lung Cancer (QLQ-LC13)

The QLQ-LC13 consisted of 1 multi-item scale and 9 single items that assessed the specific symptoms (dyspnea, cough, hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer participants receiving chemotherapy. The QLQ-LC13 Coughing, Dyspnoea and Pain in chest each ranged from 0-100 with higher scores indicating a high level of symptomatology/problems. TTD in pain in chest, dyspnea, or cough from the QLQ-LC13 was a composite endpoint defined as the time from randomization to the earliest time the participant's scale scores showed a 10 point or greater increase after baseline in any of the 3 symptoms. (NCT01639001)
Timeframe: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）

InterventionMonths (Median)
Crizotinib2.8
Chemotherapy0.3

[back to top]

Progression-Free Survival (PFS) Based on IRR by Treatment Arm

PFS was defined as the time from the date of randomization to the date of the first documentation of objective tumor progression (by IRR) or death on study due to any cause, whichever occured first. If tumor progression data included more than 1 date, the first date was used. PFS (in months) was calculated as (first event date - randomization date +1)/30.44. Progression is defined using RECIST v1.1, as at least a 20% increase (including an absolute increase of at least 5 millimeters) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. (NCT01639001)
Timeframe: Randomization to objective progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, assessed up to 33 months)

InterventionMonths (Median)
Crizotinib11.1
Chemotherapy6.8

[back to top]

Percentage of Participants With Disease Control at 12 Weeks Based on IRR

Disease Control Rate (DCR) at 12 weeks is defined as the percent of participants with CR, PR or stable disease (SD) at 12 weeks according to RECIST version 1.1 as determined by the IRR. The best response of SD can be assigned if SD criteria were met at least once after randomization at a minimum interval of 6 weeks. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis <10 mm). No new lesions and disappearance of all non-target lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. (NCT01639001)
Timeframe: From randomization to Week 12

InterventionPercentage of participants (Number)
Crizotinib82.7
Chemotherapy73.8

[back to top]

Overall Survival (OS)

OS was defined as the time from randomization to the date of death due to any cause. OS (in months) was calculated as (date of death - date of randomization +1)/30.44. For participants who were lost to follow-up or withdrew consent, the OS was censored on the last date that participants were known to be alive. (NCT01639001)
Timeframe: From randomization to death or last date known as alive for those who were lost to follow-up or withdrew consent (assessed up to 64 months).

InterventionMonths (Median)
Crizotinib33.7
Chemotherapy32.9

[back to top]

Time to Tumor Response (TTR) Based on IRR

TTR was defined as the time from randomization to first documentation of objective tumor response (CR or PR) as determined by the IRR. For participants proceeding from PR to CR, the onset of PR was taken as the onset of response. TTR was calculated for the subgroup of participants with objective tumor response. (NCT01639001)
Timeframe: Randomization to first documentation of objective tumor response (up to 33 months).

InterventionWeeks (Median)
Crizotinib6.3
Chemotherapy12.1

[back to top]

Intracranial Time to Progression (IC-TTP) Based on IRR

IC-TTP was defined similarly to TTP, but only considering intracranial disease (excluding extracranial disease) and the progression was determined based on either new brain metastases or progression of existing brain metastases. (NCT01639001)
Timeframe: Randomization to objective intracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)

InterventionMonths (Median)
CrizotinibNA
Chemotherapy16.0

[back to top]

Extracranial Time to Progression (EC-TTP) Based on IRR

EC-TTP was defined similarly to TTP, but only considering extracranial disease (excluding intracranial disease) and the progression was determined based on either new extracranial lesions or progression of existing extracranial lesions. (NCT01639001)
Timeframe: Randomization to objective extracranial progression or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)

InterventionMonths (Median)
Crizotinib18.0
Chemotherapy7.0

[back to top]

Duration of Response (DR) Based on IRR

DR was defined as the time from the first documentation of objective tumor response (CR or PR), as determined by the IRR, to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. If tumor progression data included more than 1 date, the first date was used. DR (in weeks) was calculated as (first date of PD or death - first date of CR or PR +1)/7. DR was only calculated for the subgroup of participants with an objective tumor response. (NCT01639001)
Timeframe: From objective response to date of progression, death or last tumor assessment without progression before any additional anti-cancer therapy (whichever occurred first, up to 33 months)

InterventionWeeks (Median)
Crizotinib44.4
Chemotherapy18.1

[back to top]

Change From Baseline in General Health Status as Assessed by EuroQol 5D (EQ-5D)-Visual Analog Scale (VAS)

EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a visual analog scale (VAS). The VAS component rates current health state on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. (NCT01639001)
Timeframe: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）

InterventionUnits on a scale (Mean)
Crizotinib3.4209
Chemotherapy-0.4927

[back to top]

Change From Baseline in General Health Status as Assessed by EQ-5D-Index

EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a visual analog scale (VAS). EQ-5D summary index is obtained with a formula that weights each level of the 5 dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health). (NCT01639001)
Timeframe: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months)

InterventionUnits on a scale (Mean)
Crizotinib0.0502
Chemotherapy0.0077

[back to top]

Percentage of Participants With Visual Disturbance as Assessed by Visual Symptom Assessment Questionnaire (VSAQ-ALK)

"VSAQ-ALK is a self-report measure that was developed to assess the problems of visual disturbances and symptoms may include the appearance of overlapping shadows and after images; shimmering, flashing or trailing lights; strings, streamers, or floaters; as well as hazy or blurry vision. The participants answered Yes to the first question (Q1) of VSAQ-ALK Have you experienced any visual disturbances? were considered to have experienced visual disturbance and were instructed to complete the rest of the questionnaire. The percentage of participants who responded to Q1 of VSAQ-ALK as Yes and as No during each study cycle was calculated as (n/N*)*100 where N* was the number of participants who had completed Q1." (NCT01639001)
Timeframe: Cycle 1 Day 1 to end of treatment or withdrawal, no later than 4 weeks (+/- 1 week) from last dose of study medication or when the decision was taken to withdraw from the study (whichever was sooner, assessed up to Cycle 86)

InterventionPercentage of participants (Number)
Baseline: Cycle 1/Day 1 (Answer to Q1: Yes)Baseline: Cycle 1/Day 1 (Answer to Q1: No)Cycle 2/Day 1 (Answer to Q1: Yes)Cycle 2/Day 1 (Answer to Q1: No)Cycle 3/Day 1 (Answer to Q1: Yes)Cycle 3/Day 1 (Answer to Q1: No)Cycle 4/Day 1 (Answer to Q1: Yes)Cycle 4/Day 1 (Answer to Q1: No)Cycle 5/Day 1 (Answer to Q1: Yes)Cycle 5/Day 1 (Answer to Q1: No)Cycle 6/Day 1 (Answer to Q1: Yes)Cycle 6/Day 1 (Answer to Q1: No)Cycle 7/Day 1 (Answer to Q1: Yes)Cycle 7/Day 1 (Answer to Q1: No)Cycle 8/Day 1 (Answer to Q1: Yes)Cycle 8/Day 1 (Answer to Q1: No)Cycle 9/Day 1 (Answer to Q1: Yes)Cycle 9/Day 1 (Answer to Q1: No)Cycle 10/Day 1 (Answer to Q1: Yes)Cycle 10/Day 1 (Answer to Q1: No)Cycle 11/Day 1 (Answer to Q1: Yes)Cycle 11/Day 1 (Answer to Q1: No)Cycle 12/Day 1 (Answer to Q1: Yes)Cycle 12/Day 1 (Answer to Q1: No)Cycle 13/Day 1 (Answer to Q1: Yes)Cycle 13/Day 1 (Answer to Q1: No)Cycle 14/Day 1 (Answer to Q1: Yes)Cycle 14/Day 1 (Answer to Q1: No)Cycle 15/Day 1 (Answer to Q1: Yes)Cycle 15/Day 1 (Answer to Q1: No)Cycle 16/Day 1 (Answer to Q1: Yes)Cycle 16/Day 1 (Answer to Q1: No)Cycle 17/Day 1 (Answer to Q1: Yes)Cycle 17/Day 1 (Answer to Q1: No)Cycle 18/Day 1 (Answer to Q1: Yes)Cycle 18/Day 1 (Answer to Q1: No)Cycle 19/Day 1 (Answer to Q1: Yes)Cycle 19/Day 1 (Answer to Q1: No)Cycle 20/Day 1 (Answer to Q1: Yes)Cycle 20/Day 1 (Answer to Q1: No)Cycle 21/Day 1 (Answer to Q1: Yes)Cycle 21/Day 1 (Answer to Q1: No)Cycle 22/Day 1 (Answer to Q1: Yes)Cycle 22/Day 1 (Answer to Q1: No)Cycle 23/Day 1 (Answer to Q1: Yes)Cycle 23/Day 1 (Answer to Q1: No)Cycle 24/Day 1 (Answer to Q1: Yes)Cycle 24/Day 1 (Answer to Q1: No)Cycle 25/Day 1 (Answer to Q1: Yes)Cycle 25/Day 1 (Answer to Q1: No)Cycle 26/Day 1 (Answer to Q1: Yes)Cycle 26/Day 1 (Answer to Q1: No)Cycle 27/Day 1 (Answer to Q1: Yes)Cycle 27/Day 1 (Answer to Q1: No)Cycle 28/Day 1 (Answer to Q1: Yes)Cycle 28/Day 1 (Answer to Q1: No)Cycle 29/Day 1 (Answer to Q1: Yes)Cycle 29/Day 1 (Answer to Q1: No)Cycle 30/Day 1 (Answer to Q1: Yes)Cycle 30/Day 1 (Answer to Q1: No)Cycle 31/Day 1 (Answer to Q1: Yes)Cycle 31/Day 1 (Answer to Q1: No)Cycle 32/Day 1 (Answer to Q1: Yes)Cycle 32/Day 1 (Answer to Q1: No)Cycle 33/Day 1 (Answer to Q1: Yes)Cycle 33/Day 1 (Answer to Q1: No)Cycle 34/Day 1 (Answer to Q1: Yes)Cycle 34/Day 1 (Answer to Q1: No)Cycle 35/Day 1 (Answer to Q1: Yes)Cycle 35/Day 1 (Answer to Q1: No)Cycle 36/Day 1 (Answer to Q1: Yes)Cycle 36/Day 1 (Answer to Q1: No)Cycle 37/Day 1 (Answer to Q1: Yes)Cycle 37/Day 1 (Answer to Q1: No)Cycle 38/Day 1 (Answer to Q1: Yes)Cycle 38/Day 1 (Answer to Q1: No)Cycle 39/Day 1 (Answer to Q1: Yes)Cycle 39/Day 1 (Answer to Q1: No)Cycle 40/Day 1 (Answer to Q1: Yes)Cycle 40/Day 1 (Answer to Q1: No)Cycle 41/Day 1 (Answer to Q1: Yes)Cycle 41/Day 1 (Answer to Q1: No)Cycle 42/Day 1 (Answer to Q1: Yes)Cycle 42/Day 1 (Answer to Q1: No)Cycle 43/Day 1 (Answer to Q1: Yes)Cycle 43/Day 1 (Answer to Q1: No)Cycle 44/Day 1 (Answer to Q1: Yes)Cycle 44/Day 1 (Answer to Q1: No)Cycle 45/Day 1 (Answer to Q1: Yes)Cycle 45/Day 1 (Answer to Q1: No)Cycle 46/Day 1 (Answer to Q1: Yes)Cycle 46/Day 1 (Answer to Q1: No)Cycle 47/Day 1 (Answer to Q1: Yes)Cycle 47/Day 1 (Answer to Q1: No)Cycle 48/Day 1 (Answer to Q1: Yes)Cycle 48/Day 1 (Answer to Q1: No)Cycle 49/Day 1 (Answer to Q1: Yes)Cycle 49/Day 1 (Answer to Q1: No)Cycle 50/Day 1 (Answer to Q1: Yes)Cycle 50/Day 1 (Answer to Q1: No)Cycle 51/Day 1 (Answer to Q1: Yes)Cycle 51/Day 1 (Answer to Q1: No)Cycle 52/Day 1 (Answer to Q1: Yes)Cycle 52/Day 1 (Answer to Q1: No)Cycle 53/Day 1 (Answer to Q1: Yes)Cycle 53/Day 1 (Answer to Q1: No)Cycle 54/Day 1 (Answer to Q1: Yes)Cycle 54/Day 1 (Answer to Q1: No)Cycle 55/Day 1 (Answer to Q1: Yes)Cycle 55/Day 1 (Answer to Q1: No)Cycle 56/Day 1 (Answer to Q1: Yes)Cycle 56/Day 1 (Answer to Q1: No)Cycle 57/Day 1 (Answer to Q1: Yes)Cycle 57/Day 1 (Answer to Q1: No)Cycle 58/Day 1 (Answer to Q1: Yes)Cycle 58/Day 1 (Answer to Q1: No)Cycle 59/Day 1 (Answer to Q1: Yes)Cycle 59/Day 1 (Answer to Q1: No)Cycle 60/Day 1 (Answer to Q1: Yes)Cycle 60/Day 1 (Answer to Q1: No)Cycle 61/Day 1 (Answer to Q1: Yes)Cycle 61/Day 1 (Answer to Q1: No)Cycle 62/Day 1 (Answer to Q1: Yes)Cycle 62/Day 1 (Answer to Q1: No)Cycle 63/Day 1 (Answer to Q1: Yes)Cycle 63/Day 1 (Answer to Q1: No)Cycle 64/Day 1 (Answer to Q1: Yes)Cycle 64/Day 1 (Answer to Q1: No)Cycle 65/Day 1 (Answer to Q1: Yes)Cycle 65/Day 1 (Answer to Q1: No)Cycle 66/Day 1 (Answer to Q1: Yes)Cycle 66/Day 1 (Answer to Q1: No)Cycle 67/Day 1 (Answer to Q1: Yes)Cycle 67/Day 1 (Answer to Q1: No)Cycle 68/Day 1 (Answer to Q1: Yes)Cycle 68/Day 1 (Answer to Q1: No)Cycle 69/Day 1 (Answer to Q1: Yes)Cycle 69/Day 1 (Answer to Q1: No)Cycle 70/Day 1 (Answer to Q1: Yes)Cycle 70/Day 1 (Answer to Q1: No)Cycle 71/Day 1 (Answer to Q1: Yes)Cycle 71/Day 1 (Answer to Q1: No)Cycle 72/Day 1 (Answer to Q1: Yes)Cycle 72/Day 1 (Answer to Q1: No)Cycle 73/Day 1 (Answer to Q1: Yes)Cycle 73/Day 1 (No)Cycle 74/Day 1 (Answer to Q1: Yes)Cycle 74/Day 1 (Answer to Q1: No)Cycle 75/Day 1 (Answer to Q1: Yes)Cycle 75/Day 1 (Answer to Q1: No)Cycle 76/Day 1 (Answer to Q1: Yes)Cycle 76/Day 1 (Answer to Q1: No)Cycle 77/Day 1 (Answer to Q1: Yes)Cycle 77/Day 1 (Answer to Q1: No)Cycle 78/Day 1 (Answer to Q1: Yes)Cycle 78/Day 1 (Answer to Q1: No)Cycle 79/Day 1 (Answer to Q1: Yes)Cycle 79/Day 1 (Answer to Q1: No)Cycle 80/Day 1 (Answer to Q1: Yes)Cycle 80/Day 1 (Answer to Q1: No)Cycle 81/Day 1 (Answer to Q1: Yes)Cycle 81/Day 1 (Answer to Q1: No)Cycle 82/Day 1 (Answer to Q1: Yes)Cycle 82/Day 1 Answer to Q1: (No)Cycle 83/Day 1 (Answer to Q1: Yes)Cycle 83/Day 1 (Answer to Q1: No)Cycle 84/Day 1 (Answer to Q1: Yes)Cycle 84/Day 1 (Answer to Q1: No)Cycle 86/Day 1 (Answer to Q1: Yes)Cycle 86/Day 1 (Answer to Q1: No)
Crizotinib6.893.251.049.046.153.943.956.135.864.237.462.636.064.028.171.924.175.923.976.123.576.521.378.825.374.727.073.028.271.828.671.428.671.428.471.628.171.927.972.130.569.529.170.928.671.431.568.532.167.928.871.228.072.030.070.030.070.032.068.024.575.525.075.028.371.727.372.728.671.426.873.227.073.024.375.730.369.725.075.032.367.725.874.224.175.930.070.025.075.027.672.426.973.129.670.429.270.829.270.826.173.929.270.825.075.036.463.629.470.638.961.120.080.035.364.721.478.637.562.523.176.937.562.521.478.635.764.321.478.630.869.225.075.030.869.225.075.030.869.230.070.022.277.822.277.825.075.022.277.816.783.337.562.520.080.020.080.00.0100.00.0100.00.0100.00.0100.00.0100.00.0100.0

[back to top]

Percentage of Participants With Visual Disturbance as Assessed by Visual Symptom Assessment Questionnaire (VSAQ-ALK)

"VSAQ-ALK is a self-report measure that was developed to assess the problems of visual disturbances and symptoms may include the appearance of overlapping shadows and after images; shimmering, flashing or trailing lights; strings, streamers, or floaters; as well as hazy or blurry vision. The participants answered Yes to the first question (Q1) of VSAQ-ALK Have you experienced any visual disturbances? were considered to have experienced visual disturbance and were instructed to complete the rest of the questionnaire. The percentage of participants who responded to Q1 of VSAQ-ALK as Yes and as No during each study cycle was calculated as (n/N*)*100 where N* was the number of participants who had completed Q1." (NCT01639001)
Timeframe: Cycle 1 Day 1 to end of treatment or withdrawal, no later than 4 weeks (+/- 1 week) from last dose of study medication or when the decision was taken to withdraw from the study (whichever was sooner, assessed up to Cycle 86)

InterventionPercentage of participants (Number)
Baseline: Cycle 1/Day 1 (Answer to Q1: Yes)Baseline: Cycle 1/Day 1 (Answer to Q1: No)Cycle 2/Day 1 (Answer to Q1: Yes)Cycle 2/Day 1 (Answer to Q1: No)Cycle 3/Day 1 (Answer to Q1: Yes)Cycle 3/Day 1 (Answer to Q1: No)Cycle 4/Day 1 (Answer to Q1: Yes)Cycle 4/Day 1 (Answer to Q1: No)Cycle 5/Day 1 (Answer to Q1: Yes)Cycle 5/Day 1 (Answer to Q1: No)Cycle 6/Day 1 (Answer to Q1: Yes)Cycle 6/Day 1 (Answer to Q1: No)
Chemotherapy7.192.913.486.611.188.914.885.213.586.510.189.9

[back to top]

Percentage of Participants With Treatment-Emergent AEs (Treatment Related)

An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. Grade 3 and 4 AEs in below table indicated severe AE and life-threatening consequences respectively; Grade 5 indicated death due to AE. (NCT01639001)
Timeframe: From the first dose of study medication up to 28 days after the last dose of study medication or up to the time that a participant died or received subsequent anticancer treatment (maximum duration between first and last dose: 324.4 weeks)

,
InterventionPercentage of participants (Number)
AEsSerious AEsGrade 3/4 AEsGrade 5 AEsAEs associated with permanent discontinuationAEs associated with dose reductionAEs associated with temporary discontinuation
Chemotherapy96.03.040.601.07.931.7
Crizotinib98.18.743.31.95.813.528.8

[back to top]

Percentage of Participants With Treatment-Emergent Adverse Events (AEs; All Causalities)

An AE was an untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes: death, initial or prolonged inpatient hospitalization, life-threatening experience, persistent or significant disability/incapacity, congenital anomaly. Treatment-emergent AEs were those with initial onset or that worsen in severity after the first dose of study medication. Grade 3 and 4 AEs in below table indicated severe AE and life-threatening consequences respectively; Grade 5 indicated death due to AE. (NCT01639001)
Timeframe: From the first dose of study medication up to 28 days after the last dose of study medication or up to the time that a participant died or received subsequent anticancer treatment (maximum duration between first and last dose: 324.4 weeks)

,
InterventionPercentage of participants (Number)
AEsSAEsGrade 3/4 AEsGrade 5 AEsAEs associated with permanent discontinuationAEs associated with dose reductionAEs associated with temporary discontinuation
Chemotherapy99.012.952.52.04.07.937.6
Crizotinib99.044.258.722.126.914.439.4

[back to top]

Estimate of the Percentage of Participants Surviving at 1 Year and at 18 Months

Probability of survival 1 year and 18 month after randomization. The probability of survival at 1 year was estimated using the Kaplan Meier method and a 2-sided 95% CI for the log [-log(1-year survival probability)] was calculated using a normal approximation and then back transformed to give a CI for the 1-year survival probability itself. The probability of survival at 18 months was estimated similarly. (NCT01639001)
Timeframe: From randomization to 1 year and from randomization to 18 months

,
InterventionPercentage of paricipants (Number)
Up to 1 yearUp to 18 months
Chemotherapy79.572.1
Crizotinib79.371.2

[back to top]

Change From Baseline Scores in QLQ-C30 Symptoms as Assessed by the EORTC-QLQ-C30

EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). The QLQ-C30 Appetite loss, Constipation, Diarrhea, Dyspnea, Fatigue, Financial difficulties, Insomnia, Nausea/vomiting, and Pain each ranged from 0-100 with higher scores indicating a high level of symptomatology/problems. (NCT01639001)
Timeframe: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）

,
InterventionUnits on a scale (Mean)
QLQ-C30 Appetite lossQLQ-C30 ConstipationQLQ-C30 DiarrheaQLQ-C30 DyspneaQLQ-C30 FatigueQLQ-C30 Financial DifficultiesQLQ-C30 InsomniaQLQ-C30 Nausea and VomitingQLQ-C30 Pain
Chemotherapy4.44652.6341-0.4791-0.19032.60280.3826-1.60606.5986-0.6956
Crizotinib-1.59677.136715.3294-7.9353-3.8888-3.2339-8.38164.0796-9.1305

[back to top]

Change From Baseline in Lung Cancer Symptom Scores as Assessed by the EORTC Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13)

The QLQ-LC13 consisted of 1 multi-item scale and 9 single items that assessed the specific symptoms (dyspnea, cough, hemoptysis, and site specific pain), side effects (sore mouth, dysphagia, neuropathy, and alopecia), and pain medication use of lung cancer participants receiving chemotherapy. The QLQ-LC13 Alopecia, Coughing, Dysphagia, Dyspnoea, Haemoptysis, Pain in arm or shoulder, Pain in chest, Pain in other parts, Peripheral neuropathy, and Sore mouth each ranged from 0-100 with higher scores indicating a high level of symptomatology/problems. (NCT01639001)
Timeframe: From Baseline to deterioration while on study treatment. For participants with no deterioration, the data was censored at the last date when QLQ-LC13 assessment for pain, dyspnea, or cough was completed (assessed up to 33 months）

,
InterventionUnits on a scale (Mean)
QLQ-LC13 AlopeciaQLQ-LC13 CoughingQLQ-LC13 DysphagiaQLQ-LC13 DyspnoeaQLQ-LC13 HaemoptysisQLQ-LC13 Pain in Arm or ShoulderQLQ-LC13 Pain in ChestQLQ-LC13 Pain in Other PartsQLQ-LC13 Peripheral NeuropathyQLQ-LC13 Sore Mouth
Chemotherapy2.7710-10.27481.0535-0.4371-3.0513-2.5927-4.1328-0.25731.85193.9114
Crizotinib-2.0837-17.27040.5354-9.0842-4.3017-6.8289-8.3565-4.84750.17871.5134

[back to top]

Progression Free Survival (PFS)

Kaplan-Meier estimates of survival were calculated. The median survival times and 95% confidence intervals are presented. (NCT01649947)
Timeframe: 6 years

Interventionmonths (Median)
Cohort 2: Bevacizumab Ineligible Patients4.2
Cohort 1: Bevacizumab Eligible Patients2.9

[back to top]

Antitumor Activity, as Measured by Tumor Response Rate of Hydroxychloroquine, Paclitaxel, Carboplatin, and Bevacizumab (for Eligible Patients) in Patients With Advanced or Recurrent NSCLC Cancer

Assessed using RECIST criteria. Determined using a Simon's two-stage minimax design with a 5% significance level and 80% power. (NCT01649947)
Timeframe: 6 years

Interventionpercentage of participants (Number)
Cohort 2: Bevacizumab Ineligible Patients55
Cohort 1: Bevacizumab Eligible Patients27

[back to top]

Phase 2 Safety: Number of Subjects Reporting Adverse Events

"Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug & occurs within first 3 weeks of therapy & met at least one of the following criteria:~Grade 3 or 4 non-hematologic toxicity as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0, 2009 [NCI, 2009] with the exceptions of Grade 3 electrolyte disturbances that respond to correction within 24 hours; or Grade 3 rash, diarrhea, nausea, vomiting and mucositis that responded to standard medical supportive care within 48 hours).~Grade 4 neutropenia lasting ≥5 days~Febrile neutropenia~Grade 3 thrombocytopenia with bleeding~Grade 4 thrombocytopenia~Grade 4 anemia~Treatment delay of >14 days due to unresolved toxicity~Alanine aminotransferase (ALT) >3 times upper limit of normal (ULN) with bilirubin >2 times ULN" (NCT01653912)
Timeframe: Up to Day 51

Interventionparticipants (Number)
TEAEsSerious TEAEsGSK2110183 Related Serious TEAEsGSK2110183 Related TEAEsStudy Treatment Related TEAEsTEAEs Leading to Discontinuation of GSK2110183TEAEs Leading to Discontinuation of Study TreatmntTEAEs Leading to Dose Modification of GSK2110183TEAEs Leading to Dose Modification of Study TrtmntTEAEs Leading to DeathDose Limiting Toxicity
Phase 2 (Treatment Group): GSK21101833016112530913172400

[back to top]

Phase 1: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade Greater Than or Equal to (≥) 3 in Severity

(NCT01653912)
Timeframe: Up to Week 3

InterventionParticipants (Number)
Subjects with at Least 1 TEAE of Grade ≥3NeutropeniaHypomagnesaemiaDiarrhoeaRash Maculo-PapularVomitingAnaemiaRashFatigueNauseaNeutropenic sepsisHyperglycemia
Phase 1 (Dose Escalation): GSK211018326126122321313

[back to top]

Phase 1 Safety: Number of Subjects Reporting Adverse Events

"Study Treatment refers to GSK2110183 with or without Carboplatin and/or Paclitaxel.~Dose limiting toxicity (DLT): An event is considered a DLT if it had a reasonable causal relationship to study drug & occurs within first 3 weeks of therapy & met at least one of the following criteria:~Grade 3 or 4 non-hematologic toxicity as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0, 2009 [NCI, 2009] with the exceptions of Grade 3 electrolyte disturbances that respond to correction within 24 hours; or Grade 3 rash, diarrhea, nausea, vomiting and mucositis that responded to standard medical supportive care within 48 hours).~Grade 4 neutropenia lasting ≥5 days~Febrile neutropenia~Grade 3 thrombocytopenia with bleeding~Grade 4 thrombocytopenia~Grade 4 anemia~Treatment delay of >14 days due to unresolved toxicity~Alanine aminotransferase (ALT) >3 times upper limit of normal (ULN) with bilirubin >2 times ULN" (NCT01653912)
Timeframe: Up to Week 3

Interventionparticipants (Number)
Treatment Emergent Adverse Events (TEAEs)Serious TEAEsGSK2110183 Related Serious TEAEsGSK2110183 Related TEAEsStudy Treatment Related TEAEsTEAEs Leading to Discontinuation of GSK2110183TEAEs Leading to Discontinuation of Study TreatmntTEAEs Leading to Dose Modification of GSK2110183TEAEs Leading to Dose Modification of Study TrtmntTEAEs Leading to DeathDose Limiting Toxicity
Phase 1 (Dose Escalation): GSK2110183291472929617182603

[back to top]

Overall Response Rate (ORR) in Phase 2 Subjects With Recurrent Platinum-resistant Ovarian Cancer (Cohort A)

"Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is Disappearance of all target lesions and Partial Response (PR) is greater than or equal to (≥) 30% decrease in the sum of the longest diameter of target lesions.~Overall Response (OR) = CR + PR." (NCT01653912)
Timeframe: Every 3 weeks up to 6 months

InterventionPercentage of participants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseNot EvaluableOverall Response Rate
Phase 2 (Treatment Group): GSK21101837.125.039.314.314.332.1

[back to top]

ORR in Phase 1 Subjects With Recurrent Platinum-resistant Ovarian Cancer

"Per RECIST version 1.1 criteria for target lesions and assessed by MRI: Complete Response (CR) is disappearance of all target lesions and Partial Response (PR) is ≥30% decrease in the sum of the longest diameter of target lesions.~Overall Response (OR) = CR + PR." (NCT01653912)
Timeframe: Up to Week 3

InterventionPercentage of participants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseNot EvaluableOverall Response Rate
Phase 1 (Dose Escalation): GSK2110183024.144.820.710.324.1

[back to top]

Progression Free Survival (PFS) by RECIST or Clinical Symptomatic Progression of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)

PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or clinical symptomatic progression or death due to any cause whichever is earlier. Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started. (NCT01653912)
Timeframe: From first dose until disease progression or death (approximately 36 months)

InterventionMonths (Median)
Phase 2 (Treatment Group): GSK21101836.5

[back to top]

Phase 1: Maximum Tolerated Dose (MTD) of GSK2110183

MTD is defined as the highest dose at which 1 or fewer of up to 6 subjects experience a dose limiting toxicity (DLT) during the first 3 weeks of combination therapy. MTD was considered exceeded if 2 or more subjects in a cohort of up to 6 subjects experienced a DLT. (NCT01653912)
Timeframe: Up to Week 3

Interventionmg (Number)
Phase 1 (Dose Escalation): GSK2110183125

[back to top]

PFS by RECIST of Subjects With Recurrent Platinum-resistant Ovarian Cancer (Phase 2-Cohort A)

PFS was defined as the number of months between date of first GSK2110183 treatment and the earliest date of disease progression by RECIST or death due to any cause whichever is earlier. Progression is defined using RECIST version 1.1 as at least a 20% increase in the sum of the longest diameter of target lesion in reference to the smallest sum of the longest diameter recorded since the treatment started. (NCT01653912)
Timeframe: From first dose until disease progression or death (approximately 36 months)

InterventionMonths (Median)
Phase 2 (Treatment Group): GSK21101837.1

[back to top]

Phase 2: Response Rate (RR) Defined by Gynecologic Cancer Intergroup (GCIG) CA 125

RR is defined by the percentage of subjects with investigator-assessed Partial Cancer Antigen (CA) 125 Response (PR) or Complete CA 125 Response (CR) at any time during the study by GCIG CA 125. PR is greater than (>) 50% decrease in CA-125 values from baseline and no clinical or radiological evidence of new lesions. CR is decrease in the CA-125 to within the normal limits and less than (<) 40 IU/mL and no clinical or radiological evidence of disease. (NCT01653912)
Timeframe: From Month 1 to 6

InterventionPercentage of participants (Number)
Complete CA 125 ResponsePartial CA 125 ResponseStable ResponseCA 125 ProgressionNot EvaluableResponse rate
Phase 2 (Treatment Group): GSK211018316.730.030.0023.346.7

[back to top]

Phase 2: Number of Subjects With Treatment-Emergent Adverse Events (TEAE) of Grade ≥3 in Severity

(NCT01653912)
Timeframe: Up to Day 21 (Phase 2)

Interventionparticipants (Number)
Subjects with at Least 1 TEAE of Grade ≥3NeutropeniaHypomagnesaemiaDiarrhoeaRash Maculo-PapularVomitingAnaemiaRashFatigueNauseaNeutropenic sepsisHyperglycemia
Phase 2 (Treatment Group): GSK21101832613654334130

[back to top]

Phase 2: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) Total Score

"The Functional Assessment of Cancer Therapy-Ovarian Cancer (FACT-O) instrument measures health related quality of life (HRQoL) in participants with ovarian cancer. The instrument is organized into sections of physical, social/family, emotional, functional well-being and ovarian subscales with a 5-point rating scale in which 0 = not at all and 4 = very much. Data presented here are change from baseline at follow-up in the FACT-O Total Score. The total score is the sum of Physical Well Being (PWB) + Social Well-being (SWB) + Emotional Well Being (EWB) + Family Well-being (FWB) + Ovarian Cancer Subscale (OCS). The FACT-O Total score range 0 - 152 with higher scores indicating better quality of life." (NCT01663857)
Timeframe: Baseline, Study Completion (up to 3 years)

Interventionunits on a scale (Mean)
LY2228820 + Gemcitabine +Carboplatin-0.6
Placebo + Gemcitabine + Carboplatin-8.9

[back to top] [back to top]

Phase 2: Overall Survival

Data presented are the median overall survival in months for participants in the Phase 2 treatment arms. (NCT01663857)
Timeframe: Baseline to Date of Death from any cause (up to 5 years)

Interventionmonths (Median)
LY2228820 + Gemcitabine +Carboplatin29.17
Placebo + Gemcitabine + Carboplatin25.10

[back to top]

Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820

PK parameters after administration of LY2228820 for both Phase 1b and Phase 2. (NCT01663857)
Timeframe: Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD

Interventionnanograms * hr per milliliter (ng*hr/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 3Cycle 1 Day 10Cycle 2 Day 10
200 mg LY22288203470317042703270

[back to top]

Phase 1b and 2: Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve From Time Zero to 8 Hours (AUC 0-8) of LY2228820

PK parameters after administration of LY2228820 for both Phase 1b and Phase 2. (NCT01663857)
Timeframe: Phase1b:Cycle(C)1 Day(D)1:Predose(PRD),0.5,1,2,4,6,8 hours(hr)postdose(PD); C1D10:PRD,0.5,1,2,8hrPD; C2D10:PRD,0.5,1,2,4,6,8,12hrPD; C7D3:PRD,0.5,1,2,4,6hrPD; Phase 2: C1D3:PRD,0.5,1,2,4,6,8hrPD; C1D10:PRD,0.5,1,2,4,6,8hrPD; C7D3:PRD,0.5,1,2,4,6,8hrPD

Interventionnanograms * hr per milliliter (ng*hr/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 10Cycle 2 Day 10Cycle 7 Day 3
300 mg LY22288203560935034907230

[back to top]

Phase 2: Progression-free Survival (PFS) in Participants Treated With LY2228820 Plus Gemcitabine and Carboplatin Versus Placebo Plus Gemcitabine and Carboplatin

PFS was defined as time from date of randomization to the date of investigator-determined objective progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death due to any cause, whichever occurred first. Progressive disease (PD) is defined as at least a 20% increase in the sum of the largest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. (NCT01663857)
Timeframe: Randomization to Date of Disease Progression or Death from any cause (up to 3 years)

Interventionmonths (Median)
LY2228820 + Gemcitabine +Carboplatin10.25
Placebo + Gemcitabine + Carboplatin8.44

[back to top]

Phase 2: Percentage of Participants Who Achieve Complete Response or Partial Response (Overall Response Rate)

Overall Response Rate was estimated as the percentage of participants with best response of Complete Response (CR) or Partial Response (PR), based on RECIST version 1.1 divided by the total number of randomized participants. CR is defined as disappearance of all target lesions. PR is defined as at least 30% disease in the sum of the largest diameter (LD) of target lesions, taking as reference the baseline sum LD. (NCT01663857)
Timeframe: Baseline to Disease Progression (up to 3 years)

Interventionpercentage of participants (Number)
LY2228820 + Gemcitabine +Carboplatin46.6
Placebo + Gemcitabine + Carboplatin46.2

[back to top]

Clinical Benefit Rate

Clinical benefit rate (CBR) was defined as the proportion of subjects who experienced a best overall response of complete response/full response or partial response (confirmed by a subsequent assessment at least 28 days later), or documented stable disease for at least 3 months after the first dose. Response categories were determined based on RECIST v1.1 criteria, then based on modified Rustin (CA-125) criteria if assessment could not be made using RECIST criteria. (NCT01696032)
Timeframe: Up to 24 months

InterventionPercent of participants (Number)
Stage 1: Guadecitabine+Carboplatin 30 mg/m243
Stage 1: Guadecitabine+Carboplatin 45 mg/m250
Stage 2: Guadecitabine+Carboplatin 30 mg/m241
Stage 2: Treatment Choice29
Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m219

[back to top]

Overall Survival

Overall survival was defined as the number of days from the day the participant was administered the first dose of study treatment to the date of death (regardless of cause). Survival time was censored on the last date the participant was known to be alive or lost to follow-up before reaching the event of death; in the TC group, time was censored at the date of crossover. (NCT01696032)
Timeframe: Up to 24 months

InterventionDays (Median)
Stage 1: Guadecitabine+Carboplatin 30 mg/m2341
Stage 1: Guadecitabine+Carboplatin 45 mg/m2195
Stage 2: Guadecitabine+Carboplatin 30 mg/m2331
Stage 2: Treatment Choice221
Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2279

[back to top]

Progression Free Survival at 6 Months

Progression free survival rate at 6 months is the proportion of participants who were alive and did not have disease progression at 6 months after start of treatment. (NCT01696032)
Timeframe: 6 months

InterventionPercent of participants (Number)
Stage 1: Guadecitabine+Carboplatin 30 mg/m20.36
Stage 1: Guadecitabine+Carboplatin 45 mg/m20.33
Stage 2: Guadecitabine+Carboplatin 30 mg/m20.37
Stage 2: Treatment Choice0.11
Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m20.19

[back to top]

Stage 1: Dose Limiting Toxicities

Number of participants with dose limiting toxicities (DLTs) in Stage 1 (NCT01696032)
Timeframe: Up to 12 months

InterventionParticipants (Count of Participants)
Stage 1: Guadecitabine+Carboplatin 30 mg/m20
Stage 1: Guadecitabine+Carboplatin 45 mg/m24

[back to top]

Stage 2: Progression Free Survival

Progression free survival (PFS) time was defined as the time interval from the date of the first dose of study medication until the earlier of disease progression or death. Participants were treated with their assigned treatment [guadecitabine+carboplatin (G+C) or treatment choice (TC)] until disease progression or unacceptable treatment-related toxicity occurred. (NCT01696032)
Timeframe: Up to 24 months

InterventionDays (Median)
Stage 2: Guadecitabine+Carboplatin 30 mg/m2114
Stage 2: Treatment Choice64

[back to top]

Stage 1: Pharmacokinetic Parameter AUC0-8

Area under the concentration-time curve from 0 to 8 hours (AUC0-8) for guadecitabine, decitabine and carboplatin (NCT01696032)
Timeframe: Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)

,
InterventionHours*ng/mL (Mean)
GuadecitabineDecitabineCarboplatin
Stage 1: Guadecitabine+Carboplatin 30 mg/m223971.151200
Stage 1: Guadecitabine+Carboplatin 45 mg/m241612941900

[back to top]

Stage 1: Pharmacokinetic Parameter Cmax

Time to maximum plasma concentration for guadecitabine, decitabine and carboplatin (NCT01696032)
Timeframe: Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)

,
Interventionng/mL (Mean)
GuadecitabineDecitabineCarboplatin
Stage 1: Guadecitabine+Carboplatin 30 mg/m296.222.619600
Stage 1: Guadecitabine+Carboplatin 45 mg/m210926.321900

[back to top]

Stage 1: Pharmacokinetic Parameter Tmax

Time to last measurable concentration for guadecitabine, decitabine and carboplatin (NCT01696032)
Timeframe: Pre-dose and up to 8 hours post-dose on Cycle 1 Day 1 for guadecitabine and decitabine and Day 8 for carboplatin (28 day cycles)

,
InterventionHours (Median)
GuadecitabineDecitabineCarboplatin
Stage 1: Guadecitabine+Carboplatin 30 mg/m21.421.981.03
Stage 1: Guadecitabine+Carboplatin 45 mg/m21.983.951.05

[back to top]

CA-125 Levels

Percentage of participants with CA-125 reduction by ≥ 50% from baseline (NCT01696032)
Timeframe: Up to 24 months

InterventionPercent of participants (Number)
Stage 1: Guadecitabine+Carboplatin 30 mg/m227
Stage 1: Guadecitabine+Carboplatin 45 mg/m250
Stage 2: Guadecitabine+Carboplatin 30 mg/m236
Stage 2: Treatment Choice32
Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m229

[back to top]

Duration of Response

Duration of response is defined as the time between the date of the first documentation of complete response/full response or partial response, and the date of disease progression or date of death due to any cause, or the last adequate tumor assessment prior to the start of subsequent anti-cancer therapy including crossing over to G+C from TC arm, whichever occurred earlier. Only participants who responded were included in the duration of response calculation. (NCT01696032)
Timeframe: Up to 24 months

InterventionDays (Median)
Stage 1: Guadecitabine+Carboplatin 30 mg/m2225
Stage 1: Guadecitabine+Carboplatin 45 mg/m2195
Stage 2: Guadecitabine+Carboplatin 30 mg/m2186
Stage 2: Treatment Choice173
Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m2182

[back to top]

Objective Response Rate

The objective response rate (ORR) was defined as the proportion of participants who experienced an objective response (best overall response of complete response/full response or partial response, which was confirmed by a subsequent assessment at least 28 days later). Response categories were determined based on RECIST v1.1 criteria, or on modified Rustin (CA-125) criteria if response assessment could not be made using RECIST criteria. (NCT01696032)
Timeframe: Up to 24 months

InterventionPercent (Number)
Stage 1: Guadecitabine+Carboplatin 30 mg/m221
Stage 1: Guadecitabine+Carboplatin 45 mg/m20
Stage 2: Guadecitabine+Carboplatin 30 mg/m216
Stage 2: Treatment Choice8
Stage 2: Crossover Treatment Choice to Guadecitabine+Carboplatin 30 mg/m24

[back to top]

Best Overall Response (BOR) - Initial Treatment Period

BOR was assessed by independent radiology review using RECIST 1.1 and was recorded from randomization until the last imaging assessment in this period. Response categories included: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. BOR for the Initial Treatment Period was based on IRO. BOR for participants during the Initial Treatment Period is presented. (NCT01704287)
Timeframe: Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)

,,
InterventionPercentage of Participants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseNot EvaluableNo DiseaseNo Assessment
Investigator-Choice Chemotherapy (ICC)0.04.519.061.515.10.00.0
Pembrolizumab 10 mg/kg7.220.414.947.59.90.00.0
Pembrolizumab 2 mg/kg3.318.916.746.713.30.60.6

[back to top]

Best Overall Response (BOR) - Switch-to-Pembrolizumab Treatment Period

The BOR was assessed using RECIST 1.1 and was recorded from the start of the second line of study drug (pembrolizumab) until the last imaging assessment in this period. Response categories included: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD): at least a 20% increase in the sum of diameters of target lesions; and Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For the switch-to-pembrolizumab treatment groups, BOR was based on independent review committee (IRC) assessment. The BOR for switched-to pembrolizumab treatment groups is presented. (NCT01704287)
Timeframe: Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)

,
InterventionPercentage of Participants (Number)
Complete ResponsePartial ResponseStable DiseaseProgressive DiseaseNot EvaluableNo Assessment
ICC→Pembrolizumab 10 mg/kg4.413.311.155.613.32.2
ICC→Pembrolizumab 2 mg/kg1.917.015.154.711.30.0

[back to top]

Interim Overall Survival (OS) - Initial Treatment Period

OS was defined as the time from randomization to death due to any cause. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS based on the product-limit (Kaplan-Meier) method for censored data is presented. This was the interim analysis for OS. (NCT01704287)
Timeframe: Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)

InterventionMonths (Median)
Pembrolizumab 2 mg/kg13.4
Pembrolizumab 10 mg/kg14.7
Investigator-Choice Chemotherapy (ICC)11.0

[back to top]

Final Overall Survival (OS) - Initial Treatment Period

OS was defined as the time from randomization to death due to any cause. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS duration based on the product-limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for OS. (NCT01704287)
Timeframe: Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019)

InterventionMonths (Median)
Pembrolizumab 2 mg/kg13.4
Pembrolizumab 10 mg/kg14.7
Investigator-Choice Chemotherapy (ICC)11.0

[back to top]

Number of Participants Who Discontinued Study Drug Due to an Adverse Event (AE) - Overall Study

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of study drug, was also an AE. The number of participants who discontinued study drug due to an AE is presented. (NCT01704287)
Timeframe: Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019)

InterventionParticipants (Count of Participants)
Pembrolizumab 2 mg/kg29
Pembrolizumab 10 mg/kg33
ICC Only13
ICC→Pembrolizumab 2 mg/kg1
ICC→Pembrolizumab 10 mg/kg1
ICC→Pembrolizumab 2 mg/kg (After Switch to Pembrolizumab)4
ICC→Pembrolizumab 10 mg/kg (After Switch to Pembrolizumab)4

[back to top]

Duration of Response (DOR) - Initial Treatment Period

For participants who demonstrated a confirmed response (Complete Response [CR]: disappearance of all target lesions or Partial Response [PR]: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. DOR analysis was based on IRO assessment. Analysis of DOR was not planned or analyzed for the switch-to-pembrolizumab treatment groups. Median DOR for participants who demonstrated a confirmed response is presented. (NCT01704287)
Timeframe: Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)

InterventionMonths (Median)
Pembrolizumab 2 mg/kg22.8
Pembrolizumab 10 mg/kgNA
Investigator-Choice Chemotherapy (ICC)6.8

[back to top]

Number of Participants Who Experienced an Adverse Event (AE) - Overall Study

An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of study drug, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which was temporally associated with the use of study drug, was also an AE. Participants were included in the treatment group in which an AE was experienced. The number of participants who experienced at least one AE is presented. (NCT01704287)
Timeframe: Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019)

InterventionParticipants (Count of Participants)
Pembrolizumab 2 mg/kg172
Pembrolizumab 10 mg/kg179
ICC Only71
ICC→Pembrolizumab 2 mg/kg52
ICC→Pembrolizumab 10 mg/kg45
ICC→Pembrolizumab 2 mg/kg (After Switch to Pembrolizumab)53
ICC→Pembrolizumab 10 mg/kg (After Switch to Pembrolizumab)41

[back to top]

Overall Response Rate (ORR) - Initial Treatment Period

ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed using RECIST 1.1. Analysis of ORR was not planned or conducted for the switch-to-pembrolizumab treatment groups. The percentage of participants who experienced a CR or PR is presented. This was the final analysis for ORR. (NCT01704287)
Timeframe: Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)

InterventionPercentage of Participants (Number)
Pembrolizumab 2 mg/kg22.2
Pembrolizumab 10 mg/kg27.6
Investigator-Choice Chemotherapy (ICC)4.5

[back to top]

Progression-free Survival (PFS) - Initial Treatment Period

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. Analysis of PFS was based on an integrated radiology and oncology (IRO) assessment and was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median PFS based on the product limit (Kaplan-Meier) method for censored data is presented. This was the final analysis for PFS. (NCT01704287)
Timeframe: Up to approximately 36 months (Through Final Analysis database cutoff date of 16-Nov-2015)

InterventionMonths (Median)
Pembrolizumab 2 mg/kg2.9
Pembrolizumab 10 mg/kg3.0
Investigator-Choice Chemotherapy (ICC)2.8

[back to top]

Final Overall Survival (OS) By Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Status - Initial Treatment Period

OS was defined as the time from randomization to death due to any cause. Participants with an Allred Proportion Score (APS) ≥2 (membranous staining in ≥1% of cells for PD-L1) were considered to be PD-L1 Positive and participants with an APS of 0 or 1 were considered to be PD-L1 Negative. Analysis of OS was not planned or conducted for the switch-to-pembrolizumab treatment groups. Median OS duration based on the product-limit (Kaplan-Meier) method for censored data by PD-L1 tumor expression status is presented. (NCT01704287)
Timeframe: Up to approximately 75 months (Through End of Trial Analysis database cutoff date of 31-Jan-2019)

,,
InterventionMonths (Median)
PD-L1 PositivePD-L1 Negative
Investigator-Choice Chemotherapy (ICC)12.19.3
Pembrolizumab 10 mg/kg17.513.4
Pembrolizumab 2 mg/kg15.010.5

[back to top]

Change in MD Anderson Dysphagia Inventory (MDADI) From Baseline

MDADI is a questionnaire of 20 questions and contains a global subscale, and three other categories of questions (emotional, functional, and physical). The scores are summed and a mean score is calculated. This mean score was multiplied by 20 to obtain a score, with a range of 0 (extremely low functioning) to 100 (high functioning). Thus, a higher MDADI score represented better day-to-day functioning and better QOL. (NCT01706939)
Timeframe: Baseline and 5 years

Interventionscore on a scale (Mean)
Reduced Dose Radiation-8.12
Standard Dose Radiation-8.93

[back to top]

Biomarkers Predictive of Failure

To determine biomarkers predictive of failure with either reduced or standard dose radiotherapy. (NCT01706939)
Timeframe: at 5 years

Interventionbiomarkers (Number)
Reduced Dose Radiation0
Standard Dose Radiation0

[back to top]

Change in Xerostomia Questionnaire (XQ)

XQ is a nine questions survey developed specifically for xerostomia symptoms. The scores are summed and a mean score is calculated on a scale of 0 (low xerostomia interference) to 10 (high xerostomia interference). A lower or negative score reflects a better quality of life compared to baseline. (NCT01706939)
Timeframe: Baseline and 5 years

Interventionscore on a scale (Mean)
Reduced Dose Radiation2.18
Standard Dose Radiation4.38

[back to top]

Number of Participants With Acute Toxicity of Chemoradiotherapy (CRT)

Number of participants with acute toxicity treated with reduced or standard dose CRT. (NCT01706939)
Timeframe: at 5 years

InterventionParticipants (Count of Participants)
Reduced Dose Radiation3
Standard Dose Radiation1

[back to top]

Number of Participants With Local-regional Control

Local-regional control (LRC) at 3 years in patients with advanced HPV related oropharynx cancer or unknown primary treated with reduced or standard dose radiation. (NCT01706939)
Timeframe: at 3 years

InterventionParticipants (Count of Participants)
Reduced Dose Radiation10
Standard Dose Radiation7

[back to top]

Change in European Organization for Research and Treatment of Cancer Questionnaire for Head and Neck (EORTC HN)

The EORTC Head and Neck module was specifically designed and validated for head and neck cancer patients. This 35-item questionnaire contains 7 symptom scales (pain, swallowing, senses, speech, social eating, social contact, and sexuality), 6 single-item scales (difficulties of teeth, mouth opening, dry mouth, sticky saliva, coughing, and feeling ill), and 5 items about the additional use of pain medicine, nutritional supplements, and feeding tube and changes in body weight. All items were transformed to scales from 0 to 100, and divided into respective sub-scores of global health (GHS), functional (FS), and symptom scale (SS). Subscales from 0-100. A high score on global health and functional scale represents a better level of functioning, whereas a high score on a symptom scale and head and neck module indicates more severe symptoms. (NCT01706939)
Timeframe: Baseline and 5 years

,
Interventionscore on a scale (Mean)
EORTC GHSEORTC FSEORTC SSEORTC HN
Reduced Dose Radiation5.955.14-3.91-2.80
Standard Dose Radiation-30.56-6.3314.978.97

[back to top]

Change in MD Anderson Symptom Inventory Symptom Inventory and Severity (MDASI-HN SI and SS)

"MD Anderson Symptom Inventory Symptom Inventory and Severity (MDASI-HN SI and SS) MDASI Head and Neck is a site-specific MDASI module which includes the core MDASI 13 symptom severity items (SS) and 6 symptom interference items (SI), alongside 9 items relevant to head and neck cancer. The scores are summed and a mean score is calculated on a scale of 0 (low severity or interference) to 10 (high severity or complete interference). In order to calculate the mean score, a majority of the subscale's items must have been completed.~A lower or negative score reflects a better quality of life compared to baseline." (NCT01706939)
Timeframe: Baseline and 5 years

,
Interventionscore on a scale (Mean)
MDASI-HN SIMDASI-HN SS
Reduced Dose Radiation0.640.52
Standard Dose Radiation1.561.48

[back to top]

Number of Participants With Progression Free Survival (PFS)

Progression free survival (PFS) at 5 years in patients with advanced HPV related oropharynx cancer, nasopharynx cancer or unknown primary treated with reduced or standard dose radiation. (NCT01706939)
Timeframe: at 3 and 5 years

,
InterventionParticipants (Count of Participants)
at 3 yearsat 5 years
Reduced Dose Radiation1010
Standard Dose Radiation77

[back to top]

Number of Participants With Overall Survival at 5 Years

Overall Survival (OS) 5 years treated with reduced or standard dose CRT. (NCT01706939)
Timeframe: at 5 years

InterventionParticipants (Count of Participants)
Reduced Dose Radiation10
Standard Dose Radiation7

[back to top]

Toxicity (Phase I and Phase II)

Adverse Events were collected each cycle during treatment and follow-up according to the CTCAE v4.0 guidelines. The worst graded adverse event was determined for each patient. Below is a table of the number of patients that reported a Grade 3 or Grade 4 or Grade 5 as their worst reported event. (NCT01711541)
Timeframe: upt to 5 years

,,,,
InterventionParticipants (Count of Participants)
Grade 3 Adverse EventGrade 4 Adverse EventGrade 5 Adverse Event
Dose Level 0030
Dose Level 0B210
Dose Level 1210
Dose Level 2400
Dose Level 3610

[back to top]

Dose Limiting Toxicity (Phase I)

"Dose Limiting Toxicity (DLTs) will be assessed during the first cycle of induction chemotherapy.~The following events are considered DLTs: Grade 4 neutropenia (ANC < 500) lasting more than 14 days, Febrile neutropenia, Grade 4 thrombocytopenia, dose delay of greater than 3 weeks due to failure to recover counts, treatment-related grade 3 or grade 4 non-hematological toxicity (excluding alopecia, fatigue, hypersensitivity reaction, nausea, vomiting, constipation, diarrhea, hypokalemia, hypomagnesemia, hypocalcemia, hypophosphatemia, and grade 3 hypertension), a dose delay of greater than 3 weeks for non-hematological toxicity despite replacement of electrolytes, maximum treatment for diarrhea, nausea, vomiting, and hypertension, any drug-related death.~The number of patients reporting a DLT are reported below. The maximum tolerated dose (MTD) will be determined as the highest dose where 1 or fewer out of 6 patients reports a DLT." (NCT01711541)
Timeframe: Up to 3 weeks

InterventionParticipants (Count of Participants)
Dose Level 00
Dose Level 0B0
Dose Level 10
Dose Level 20
Dose Level 31

[back to top]

CHFR Methylation Status

Number of participants with advanced esophagogastric cancer that are CHFR-methylated or unmethylated at baseline. (NCT01715233)
Timeframe: Baseline

InterventionParticipants (Count of Participants)
CHFR-methylatedCHFR-unmethylated
Metastatic Esophageal, Gastroesophageal & Gastric Cancer.612

[back to top]

Overall Survival

Number of participants alive at 2 years. (NCT01715233)
Timeframe: 2 Years

InterventionParticipants (Count of Participants)
Metastatic Esophageal, Gastroesophageal And Gastric Cancer.2

[back to top]

Response

Number of participants treated with mDCF with progressive disease (PD), stable disease (SD), partial response (PR), non-complete response and non-progressive disease (non-CR/non-PD), and partial response with progressive disease clinically (PR/PD) as defined by RECIST criteria. Response is compared based on CHFR-methylation status. (NCT01715233)
Timeframe: 4 months

InterventionParticipants (Count of Participants)
CHFR-methylated72174376CHFR-unmethylated72174376Unknown methylation status72174376
SDnon-CR/non-PDPR/PDPRPD
Metastatic Esophageal, Gastroesophageal & Gastric Cancer.3
Metastatic Esophageal, Gastroesophageal & Gastric Cancer.2
Metastatic Esophageal, Gastroesophageal & Gastric Cancer.1
Metastatic Esophageal, Gastroesophageal & Gastric Cancer.5
Metastatic Esophageal, Gastroesophageal & Gastric Cancer.0

[back to top]

Number of Patients With Toxicity of Concurrent Chemoradiotherapy

Assessed by NCI Common Toxicity Criteria for Adverse Effects, Version 4.0. Reported participants who experienced an AE during concurrent chemoradiotherapy. (NCT01716195)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Response Adapted Chemoradiation17

[back to top]

Number of Participants With Overall Survival

Defined as the time from registration to death using the Kaplan-Meier method.. (NCT01716195)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Response Adapted Chemoradiation16

[back to top]

Number of Participants With Progression-free Survival

Defined from date of registration to date of first documentation of progression and/or distant metastasis, or death due to any cause. The true 2-year progression-free survival rate will be estimated by the proportion of efficacy-evaluable patients on study without documentation of disease progression or death 2 years from registration. A 95% confidence interval (CI) for the true progression-free survival rate will be constructed using the Duffy-Santner approach. However, Kaplan-Meier methodology will be used to estimate the final 2-year progression-free survival rate and its 95% CI in case there are censored patients. (NCT01716195)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Response Adapted Chemoradiation17

[back to top]

Progression Free Survival (PFS)

Progression Free Survival (PFS) is defined as the time from randomization to the date of the first documented progression, as determined by the Independent Review Committee (IRC) using RECIST 1.1, or death due to any cause, whichever occurs first. Participants who died without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment before subsequent anti-cancer therapy. Unit of measure (months) is the median survival time. (NCT01721746)
Timeframe: From the date of randomization to the date of the first documented progression or death (Up to approximately 38 months)

Interventionmonths (Median)
Nivolumab3.12
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)3.65

[back to top] [back to top]

Objective Response Rate (ORR) by Baseline PD-L1 Expression

Objective Response Rate (ORR) is defined as the number of participants with a Best Overall Response (BOR) of complete response (CR) or partial response (PR) divided by number of randomized participants. PD-L1 expression evaluated for ORR. (NCT01721746)
Timeframe: From date of randomization to the date of objectively documented progression or the date of subsequent therapy (Up to approximately 38 months)

,
InterventionPercentage of participants (Number)
<5% PD-L1 expression>=5% PD-L1 expression
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)13.812.2
Nivolumab15.343.2

[back to top]

Objective Response Rate (ORR)

Objective response rate (ORR) per Independent Review Committee (IRC) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of randomized participants using RECIST 1.1 (NCT01721746)
Timeframe: From date of randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (Up to approximately 38 months)

InterventionPercentage of participants (Number)
Nivolumab27.2
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)9.8

[back to top]

Overall Survival (OS)

Overall Survival (OS) was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. Unit of measure (months) is the median survival time. (NCT01721746)
Timeframe: Up to 96 months

InterventionMonths (Median)
Nivolumab15.74
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)14.39

[back to top]

Overall Survival (OS) by PD-L1 Negative

Overall Survival (OS) by PD-L1 expression was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. (NCT01721746)
Timeframe: Up to 96 months

InterventionMonths (Median)
Nivolumab11.14
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)11.76

[back to top]

Overall Survival (OS) by PD-L1 Positive

Overall Survival (OS) by PD-L1 expression was defined the time between the date of randomization to the date of death. For participants without documentation of death, OS was censored on the last date the participant was known to be alive. (NCT01721746)
Timeframe: Up to 96 months

InterventionMonths (Median)
Nivolumab31.44
Investigator's Choice (Dacarbazine or Carboplatin+Paclitaxel)16.72

[back to top]

Phase 1b: Percentage Inhibition of Expression Levels of Gli1 in Skin Cells

The gene expression data (Gli1) was normalized and the level of percentage of Gli1 inhibition post treatment was calculated. (NCT01722292)
Timeframe: Baseline, Cycle 2 Day 1, Cycle 7 Day 1

InterventionPercentage of Gli 1 Inhibition (Median)
Phase 1b: 100 mg LY294068094.7
Phase 1b: 200 mg LY294068095.1
Phase 1b: 400 mg LY294068094.8

[back to top]

Phase 1b: Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])

ORR was defined as the percentage of all randomized participants with the best overall response of PR or CR using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Tumor marker results must have normalized. PR is at least a 30% decrease in the sum of diameter of target lesions, taking as reference the baseline sum diameters. (NCT01722292)
Timeframe: Baseline to Study Completion Up to 39 Months

Interventionpercentage of participants (Mean)
Phase 1b: 100 mg LY2940680 + C+ E50
Phase 1b: 200 mg LY2940680 + C+ E50
Phase 1b: 400 mg LY2940680 + C+ E57.1

[back to top] [back to top] [back to top] [back to top] [back to top] [back to top] [back to top] [back to top]

Maximum Tolerated Dose (MTD) of Afatinib

The maximally tolerated dose (MTD) was defined as the dose of afatinib in which <2 of 6 patients experience a DLT with the next higher dose having at least 2 of up to 6 patients experiencing a DLT. No dose escalations or de-escalations are permitted within each subject's treatment. (NCT01732640)
Timeframe: 1 Year (Average)

Interventionmg (Number)
All Study Participants20

[back to top]

Number of Participants With Dose Limiting Toxicities

Grade 3 or 4 neutropenia (ie. absolute neutrophil count <1000 cells/mm^3) that was associated with a fever>38.5 degrees C or lasting longer than 5 days, grade 3 thrombocytopenia with bleeding or grade 4 thrombocytopenia, and any grade 3 or 4 non-hematologic toxicity per CTCAE criteria which were probably or definitely related to study therapy. During the chemoradiation, an event of stomatitis, pharyngitis, mucositis, or dermatitis was not considered to be a dose limiting toxicity unless it was a grade 4 that did resolve to NCT01732640)
Timeframe: 1 year (average)

InterventionParticipants (Count of Participants)
20 mg Afatinib2
30 mg Afatinib3

[back to top]

Progression Rate

secondary outcome measure for efficacy evaluation (NCT01763645)
Timeframe: Day 127

Interventionpercentage of patients (Number)
BCD-021 (CISC BIOCAD)5.56
Avastin (F. Hoffmann-La Roche Ltd)8.93

[back to top]

Partial Response Rate

secondary outcome measure for efficacy evaluation (NCT01763645)
Timeframe: Day 127

Interventionpercentage of patients (Number)
BCD-021 (CISC BIOCAD)40.74
Avastin (F. Hoffmann-La Roche Ltd)37.50

[back to top]

Stabilization Rate

secondary outcome measure for efficacy evaluation (NCT01763645)
Timeframe: Day 127

Interventionpercentage of patients (Number)
BCD-021 (CISC BIOCAD)51.85
Avastin (F. Hoffmann-La Roche Ltd)51.79

[back to top]

Area Under the Curve After the First Test Drug Administration

primary outcome measure for pharmacokinetics (PK) substudy (NCT01763645)
Timeframe: up to Day 22, after the first bevacizumab administration (time points for blood samples: 0 h 1.5 h, 3 h, 4.5 h, 6 h, 24 h, 96 h, 168 h, 336 h and 504 h)

Intervention(ng/ml)*hour (Median)
BCD-021 (CISC BIOCAD)66869
Avastin (F. Hoffmann-La Roche Ltd)58844

[back to top]

Complete Response Rate

secondary outcome measure for efficacy evaluation (NCT01763645)
Timeframe: Day 127

Interventionpercentage of patients (Number)
BCD-021 (CISC BIOCAD)1.85
Avastin (F. Hoffmann-La Roche Ltd)1.79

[back to top]

Occurrence of Anti-bevacizumab Antibodies

Secondary outcome measure for immunogenicity assessment (NCT01763645)
Timeframe: Day 1 (before the drug administration), Day 15, 64 and 127

Interventionpercentage of patients (Number)
BCD-021 (CISC BIOCAD)1.47
Avastin (F. Hoffmann-La Roche Ltd)1.52

[back to top]

Overall Response Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT01763645)
Timeframe: Day 127

Interventionpercentage of participans (Number)
BCD-021 (CISC BIOCAD)42.59
Avastin (F. Hoffmann-La Roche Ltd)39.29

[back to top]

Overall Survival (OS)

OS defined as the time from the date of randomization to the date of death from any cause. For participants not known to have died as of the data cut-off date, OS was censored at the last contact date (last contact for participants in post-discontinuation = last known alive date in mortality status). (NCT01769391)
Timeframe: Randomization to Date of Death (Up to 24 Months)

Interventionmonths (Median)
Necitumumab +Paclitaxel+Carboplatin13.2
Paclitaxel + Carboplatin11.2

[back to top]

Percent Change in Tumor Size (CTS)

CTS is defined as maximum percent change from baseline in the sum of target lesions. (NCT01769391)
Timeframe: Baseline to Progressive Disease or Death (Up to 24 Months)

Interventionpercent change in tumor size (Mean)
Necitumumab +Paclitaxel+Carboplatin-44.3
Paclitaxel + Carboplatin-38.65

[back to top]

Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) (Objective Response Rates [ORR])

The denominator of ORR (Objective Response Rate) includes each participant enrolled who received any amount of study drug (necitumumab, gemcitabine, and/or cisplatin), and who had a complete radiographic assessment at baseline and at least one complete radiographic assessment post-baseline. The numerator includes those participants counted in the denominator with a confirmed best overall tumor response of partial or complete response (Complete Response (CR): disappearance of all non-nodal target lesions, with the short axes of any target lymph nodes reduced to <10 millimeters (mm). Partial Response (PR): at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph nodes), taking as reference the baseline sum diameter.) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. (NCT01769391)
Timeframe: Baseline to Disease Progression or Death (Up to 24 Months)

Interventionpercentage of participants (Number)
Necitumumab +Paclitaxel+Carboplatin48.9
Paclitaxel + Carboplatin40.0

[back to top]

Percentage of Participants With Anti Necitumumab Antibodies

(NCT01769391)
Timeframe: Baseline to End of Cycle 6

Interventionpercentage of participants (Number)
Necitumumab + Paclitaxel+ Carboplatin2.8

[back to top]

Progression-Free Survival

Progression-Free Survival (PFS) is defined as the time from randomization until the first radiographically documented progressive disease (PD) or death from any cause. PD defined by Response Evaluation Criteria in Solid Tumors Criteria (RECIST version 1.1) as at least a 20% increase in the sum of the diameters of target lesions,taking as reference the smallest sum on study (including the baseline sum if that is the smallest). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. For participants not known to have died as of the data cut-off date and who do not have objective PD, PFS will be censored at the date of the last complete radiographic assessment. (NCT01769391)
Timeframe: Randomization to Progressive Disease or Death (Up to 24 Months)

Interventionmonths (Median)
Necitumumab +Paclitaxel+Carboplatin5.4
Paclitaxel + Carboplatin5.6

[back to top]

Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab

(NCT01769391)
Timeframe: Pre-infusion Cycle 1, Day 1; Cycle 3, Day 1; Cycle 5; Day 1 (within 2 hours prior to beginning of infusion)

Interventionmicrogram/milliliter (μg/mL) (Geometric Mean)
Cycle 1, Day 1 (n=92)Cycle 3, Day 1 (n=72)Cycle 5, Day 1 (n=62)
Necitumumab +Paclitaxel+Carboplatin262.418296.843303.475

[back to top]

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab

(NCT01769391)
Timeframe: Cycle 1, Day 8 ; Cycle 2, Day 1; Cycle 3, Day 1;Cycle 4, Day1;Cycle 5, Day 1; Cycle 6, Day 1 (within 2 hours prior to beginning of infusion)

Interventionnanogram/milliliter (ng/mL) (Geometric Mean)
Cycle 1, Day 8 (n-85)Cycle 2, Day 1 (n=79)Cycle 3, Day 1 (n=76)Cycle 4, Day 1 (n=70)Cycle 5, Day 1 (n=62)Cycle 6, Day 1 (n=59)
Necitumumab +Paclitaxel+Carboplatin59.26947.87478.14280.39289.13787.043

[back to top]

Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])

Defined using the same denominator as defined in ORR. Among participants counted in the denominator, the numerator counts those with a confirmed best tumor response of SD, PR, or CR per RECIST 1.1. (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; PR at least 30% decrease in the sum of diameter of target lesions; CR: disappearance of all target lesions). (NCT01769391)
Timeframe: Baseline to Progressive Disease and/or Death (Estimated up to 24 Months)

Interventionpercentage of participants (Number)
Necitumumab +Paclitaxel+Carboplatin87.2
Paclitaxel + Carboplatin84.0

[back to top]

Death Rate

(NCT01779050)
Timeframe: Up to 3 years after completion of treatment (estimated to be 4 years)

InterventionParticipants (Count of Participants)
Arm I (Definitive Therapy)1
Arm II (Definitive Therapy, Trastuzumab)0

[back to top]

Number of Participants With Disease Recurrence

-Disease recurrence is defined as the documented appearance of local (breast, chest wall, axillary, supraclavicular nodes) or distant disease. (NCT01779050)
Timeframe: Up to 3 years after completion of treatment (estimated to be 4 years)

InterventionParticipants (Count of Participants)
Arm I (Definitive Therapy)1
Arm II (Definitive Therapy, Trastuzumab)0

[back to top]

Percentage of Participants Experiencing Treatment-Emergent Adverse Events

(NCT01803282)
Timeframe: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days

Interventionpercentage of participants (Number)
Part A: ADX 200 mg100.0
Part A: ADX 600 mg100.0
Part A: ADX 1800 mg83.3
Part B: PAC, ADX 800 mg100.0
Part B: LAC, ADX 1200 mg100.0
Part B: LSC, ADX 1200 mg100.0
Part B: EGC, ADX 800 mg100.0
Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg100.0
Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg100.0
Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg100.0
Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg100.0
Part B: BRCA, ADX 800 mg100.0

[back to top]

Percentage of Participants Experiencing Laboratory Abnormalities

Treatment-emergent laboratory abnormalities were defined as values that increase at least one toxicity grade from baseline. Participants with any laboratory abnormality were reported. (NCT01803282)
Timeframe: Part A: First dose date up to 32 weeks plus 30 days; Part B: First dose date up to 181 weeks plus 30 days

,,,,,,,,,,,
Interventionpercentage of participants (Number)
Any Laboratory abnormalities: HematologyAny Laboratory abnormalities: Serum ChemistryAny Laboratory abnormalities: Coagulation
Part A: ADX 1800 mg33.383.333.3
Part A: ADX 200 mg0.0100.025.0
Part A: ADX 600 mg33.366.70.0
Part B: BRCA, ADX 800 mg86.766.740.0
Part B: EGC, ADX 800 mg87.587.535.0
Part B: FL CRC, ADX 800 mg+BEV 10 mg/kg90.981.836.4
Part B: FL CRC, ADX 800 mg+BEV 5 mg/kg84.495.637.8
Part B: LAC, ADX 1200 mg90.060.010.0
Part B: LSC, ADX 1200 mg80.070.010.0
Part B: PAC, ADX 800 mg97.288.938.9
Part B: SL CRC, ADX 800 mg+BEV 10 mg/kg100.087.537.5
Part B: SL CRC, ADX 800 mg+BEV 5 mg/kg95.586.445.5

[back to top]

Objective Response Rate (ORR)

The number of patients who had at least 1 confirmed visit response of Complete Response (CR) or Partial Response (PR) prior to any evidence of progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm; Objective Response Rate (ORR) = CR + PR (NCT01809210)
Timeframe: Up until progression or last evaluable assessment in the absence of progression, up to 9 months

Interventionparticipants (Number)
Cohort 1 sel50, Gem, Cis1
Cohort 2 sel50, Gem, Carb2
Cohort 3 sel75, Gem, Cis2
Cohort 4 sel150, Pem, Carb1
Cohort 5 sel75, Pem, Carb1
Cohort 6 sel75, Pem, Cis2
Cohort 7 sel100, Pem, Carb2

[back to top]

Percentage Change From Baseline at 6 Weeks in Target Lesion Size

The percentage change in the sum of the diameters of target lesions (NCT01809210)
Timeframe: Week 6

Intervention% change (Mean)
Cohort 1 sel50, Gem, Cis-7.5
Cohort 2 sel50, Gem, Carb-29.3
Cohort 3 sel75, Gem, Cis-10.4
Cohort 4 sel150, Pem, Carb-14.7
Cohort 5 sel75, Pem, Carb-24.4
Cohort 6 sel75, Pem, Cis-18.9
Cohort 7 sel100, Pem, Carb-18.4

[back to top]

Tmax,ss

Time to reach maximum plasma concentration at steady state (NCT01809210)
Timeframe: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

Interventionh (Median)
Cohort 1 sel50, Gem, Cis1.00
Cohort 2 sel50, Gem, Carb1.25
Cohort 3 sel75, Gem, Cis1.00
Cohort 4 sel150, Pem, Carb1.00
Cohort 5 sel75, Pem, Carb1.75
Cohort 6 sel75, Pem, Cis1.48
Cohort 7 sel100, Pem, Carb1.50

[back to top]

Best Objective Response

The best response a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Per Response Evaluation Criteria In Solid Tumours (RECIST version 1.1) for target lesions (TL) and assessed by MRI or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progressive Disease (PD); Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, the sum must also demonstrate an absolute increase of >=5mm; Complete Response (CR), disappearance of all target lesions, any pathological lymph nodes selected as TLs must have a reduction in short axis to <10mm (NCT01809210)
Timeframe: Screening, week 6 and week 12

,,,,,,
Interventionparticipants (Number)
Complete responsePartial responseUnconfirmed complete or partial responseStable diseaseRECIST progressionDeathIncomplete post-baseline assessments
Cohort 1 sel50, Gem, Cis0100200
Cohort 2 sel50, Gem, Carb0231003
Cohort 3 sel75, Gem, Cis0202102
Cohort 4 sel150, Pem, Carb0102000
Cohort 5 sel75, Pem, Carb0123000
Cohort 6 sel75, Pem, Cis0227112
Cohort 7 sel100, Pem, Carb0226101

[back to top]

Dose Limiting Toxicity (DLT) Events in Chemotherapy in Combination With Selumetinib

Any toxicity not attributable to the disease or disease-related processess under investigation, considered related to the combination of chemotherapy plus selumetinib, which occurs within the timeframe and is dose limiting (NCT01809210)
Timeframe: The first dose on Cycle 1 Day 1 up to the time before dosing on Cycle 2 Day 1, assessed up to 3 weeks

,,,,,,
Interventionparticipants (Number)
Evaluable patientsEvaluable patients with a DLT Event
Cohort 1 sel50, Gem, Cis30
Cohort 2 sel50, Gem, Carb72
Cohort 3 sel75, Gem, Cis41
Cohort 4 sel150, Pem, Carb30
Cohort 5 sel75, Pem, Carb60
Cohort 6 sel75, Pem, Cis121
Cohort 7 sel100, Pem, Carb61

[back to top]

Best Percentage Change From Baseline in Target Lesion Size

The best percentage change in tumour size a patient has had during their time in the study up until RECIST progression or last valuable assessment in the absence of RECIST progression. Percentage change was derived at each visit by the percentage change in the sum of the diameters of target lesions (NCT01809210)
Timeframe: Screening, week 6 and week 12

Intervention% change (Mean)
Cohort 1 sel50, Gem, Cis-11.9
Cohort 2 sel50, Gem, Carb-34.6
Cohort 3 sel75, Gem, Cis-41.3
Cohort 4 sel150, Pem, Carb-28.3
Cohort 5 sel75, Pem, Carb-34.7
Cohort 6 sel75, Pem, Cis-24.4
Cohort 7 sel100, Pem, Carb-25.4

[back to top]

AUC (0-tau)

Area under the concentration time curve (AUC) over a dosing interval at steady state (0-tau) (NCT01809210)
Timeframe: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

Interventionh*ng/mL (Geometric Mean)
Cohort 1 sel50, Gem, CisNA
Cohort 2 sel50, Gem, Carb3571
Cohort 3 sel75, Gem, Cis3339
Cohort 4 sel150, Pem, Carb4813
Cohort 5 sel75, Pem, Carb4366
Cohort 6 sel75, Pem, Cis4116
Cohort 7 sel100, Pem, Carb5202

[back to top]

CL/F

Apparent oral plasma clearance (NCT01809210)
Timeframe: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

InterventionL/h (Mean)
Cohort 1 sel50, Gem, CisNA
Cohort 2 sel50, Gem, Carb14.72
Cohort 3 sel75, Gem, Cis22.64
Cohort 4 sel150, Pem, Carb10.72
Cohort 5 sel75, Pem, Carb18.82
Cohort 6 sel75, Pem, Cis19.08
Cohort 7 sel100, Pem, Carb21.02

[back to top]

Cmax,ss

Maximum plasma concentration at steady state (NCT01809210)
Timeframe: Cycle 2 Day1, pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 hours post dose

Interventionng/mL (Geometric Mean)
Cohort 1 sel50, Gem, Cis476.7
Cohort 2 sel50, Gem, Carb1222
Cohort 3 sel75, Gem, Cis1487
Cohort 4 sel150, Pem, Carb1615
Cohort 5 sel75, Pem, Carb1375
Cohort 6 sel75, Pem, Cis1364
Cohort 7 sel100, Pem, Carb2309

[back to top]

Count of Participants That Achieve Pathologic Complete Response (PCR)

PCR is defined as the absence of any residual invasive cancer on hematoxylin and eosin (H&E) evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes. (NCT01818063)
Timeframe: 36 months following surgery

InterventionParticipants (Count of Participants)
Arm 1 (Paclitaxel, Carboplatin)3
Arm 2 (Veliparib, Paclitaxel, Carboplatin)3

[back to top]

Number of Subjects Experiencing a Metastasis by Site of Metastasis

Number of patients experiencing a metastasis between baseline and cycle 3 (NCT01820754)
Timeframe: 3 months

InterventionParticipants (Count of Participants)
Ipilimumab1

[back to top]

Percentage of Subjects With Detectable Circulating T Cells After Treatment

"The primary objective of this trial is to determine the percentage of early stage lung cancer patients with detectable circulating T cells specific against tumor-associated antigen (TAA) after receiving platinum based neoadjuvant chemotherapy plus ipilimumab before surgery. Based on Duke intracellular cytokine staining (ICS) assessments over the past 8 years, detectable circulating T cells with specificity against TAA are defined as a CD8, CD4, and double positive (DP) (CD4+CD8+) lymphocyte percentage of ≥ 0.05% with each value also being at least twice that of the background unstimulated control value." (NCT01820754)
Timeframe: 3 months

InterventionPercentage of participants (Number)
Ipilimumab16.7

[back to top]

Feasibility and Tolerability of Neoadjuvant Chemotherapy Plus Ipilimumab and Surgery

"Number of subjects experiencing any of the criteria listed below:~Number of subjects receiving 3 doses of preoperative therapy~Number of subjects undergoing surgical exploration within 42 days of day 1 of the last cycle of neoadjuvant chemotherapy~Number of subjects undergoing lobectomy having surgery-related mortality~Number of subjects experiencing dose-limiting toxicity (DLT) during neoadjuvant therapy. DLT will be defined as treatment-related: ≥ Grade 4 hematologic toxicity (excluding neutropenia without fever or infection) or ≥ Grade 3 non-hematologic toxicity (excluding fatigue, nausea, vomiting, peripheral neuropathy, chemotherapy infusion reaction to carboplatin or paclitaxel)" (NCT01820754)
Timeframe: 6 months

InterventionParticipants (Count of Participants)
Patients receiving 3 cyclesPatients undergoing surgical explorationPatients undergoing lobectomyPatients experiencing a DLT
Ipilimumab2413113

[back to top]

Patterns of Pathologic Response and Response Evaluation Criteria in Solid Tumor (RECIST) Response

"Within each category of RECIST response [partial response (PR), stable disease (SD), progressive disease (PD)], the number of subjects experiencing a pathologic complete response, pathologic partial response, and no pathologic response. RECIST evaluation will be conducted after completion of neoadjuvant therapy. Pathologic response will be evaluated in the resected tumor as follows:~No Pathologic Response: No evidence of cell death or tumor necrosis~Pathologic Partial Response: ≥30% tumor necrosis or cell death~Pathologic Complete Response: No evidence of viable tumor in surgical specimen (includes lung tissue and dissected lymph nodes)" (NCT01820754)
Timeframe: 3 months

InterventionParticipants (Count of Participants)
PRSDPD
Ipilimumab1482

[back to top]

Percentage of Patients With Complete or Partial Response

Per the RECIST guideline v1.1 complete response is defined as the disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. No statistical testing was done due to early study termination. (NCT01822496)
Timeframe: From randomization to study termination. Maximum follow-up was 39.0 months

Interventionpercentage of participants (Number)
EGFR: Erlotinib50.0
EGFR: No Erlotinib26.7
ALK: Crizotinib66.7
ALK: No Crizotinib75.0

[back to top]

Overall Survival

Overall survival time is defined as time from randomization to the date of death from any cause. Overall survival rates are estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. (NCT01822496)
Timeframe: From randomization to study termination. Maximum follow-up was 39.0 months

InterventionMonths (Median)
EGFR: ErlotinibNA
EGFR: No Erlotinib35.9
ALK: CrizotinibNA
ALK: No CrizotinibNA

[back to top]

Number of Patients With Grade 3-5 Adverse Events

Adverse events (AE) are graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE. (NCT01822496)
Timeframe: From randomization to study termination. Maximum follow-up was 39.0 months

InterventionParticipants (Count of Participants)
EGFR: Erlotinib0
EGFR: No Erlotinib0
ALK: Crizotinib0
ALK: No Crizotinib0

[back to top]

Progression-free Survival

Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesions at any location. Progression-free survival time is measured from the date of randomization to the date of first progression, death, or last known follow-up (censored). No statistical testing was done due to early study termination. (NCT01822496)
Timeframe: From randomization to study termination. Maximum follow-up was 39.0 months

Interventionmonths (Median)
EGFR: Erlotinib21.1
EGFR: No Erlotinib9.2
ALK: Crizotinib14.7
ALK: No CrizotinibNA

[back to top]

Distant Progression-free Survival

Distant progression is defined as the first occurrence of distant metastasis. Distant progression-free survival time is measured from the date of randomization to the date of first distant progression, death, or last known follow-up (censored). Distant progression-free survival rates are estimated using the Kaplan-Meier method. No testing was done due to early study termination. (NCT01822496)
Timeframe: From randomization to study termination. Maximum follow-up was 39.0 months

InterventionMonths (Median)
EGFR: ErlotinibNA
EGFR: No Erlotinib35.9
ALK: CrizotinibNA
ALK: No Crizotinib20.1

[back to top]

Local-regional Progression-free Survival

Progression is defined using the RECIST guideline v1.1 as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new regional lesions. Local progression is defined as progression within the planning target volume (PTV). Regional progression is defined as progression outside of the PTV but within the same lobe of the lung as the primary tumor or in regional lymph nodes as defined by the American Joint Committee on Cancer (AJCC) 7th edition nodal stations. Local-regional progression-free survival time is measured from the date of randomization to the date of first local-regional progression, death, or last known follow-up (censored). Local-regional progression-free survival rates are estimated using the Kaplan-Meier method. No testing was done due to early study termination. (NCT01822496)
Timeframe: From randomization to study termination. Maximum follow-up was 39.0 months

InterventionMonths (Median)
EGFR: Erlotinib25.7
EGFR: No ErlotinibNA
ALK: Crizotinib14.7
ALK: No CrizotinibNA

[back to top]

Number of Participants With an Objective Response

ORR is the proportion of participants with a complete response (CR) or partial response (PR) per the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all tumors. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters. (NCT01827384)
Timeframe: Up to 30 days after completion of study treatment, up to 75 months

,,,,,,,,,,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial Response
TAC1 -> TAC400
TAC200
TAC2 -> TAC100
TAC2 -> TAC300
TAC301
TAC3 -> TAC100
TAC3 -> TAC1 -> TAC400
TAC3 -> TAC400
TAC400
TAC4 -> TAC100
TAC4 -> TAC200
TAC4 -> TAC300
Treatment Assignment Code 1 (TAC1)00

[back to top]

Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. (NCT01827384)
Timeframe: Date treatment consent signed to date off study, approx. 73months (m) & 21day (d); 4m & 11d; 61m & 8d; 4m & 11d; 10m & 11d; 72m & 29d; 13m & 11d; 6m & 13d; 29m & 18d; 48m & 25d; 49m & 5d; 4m &7d; 15m & 5d; and 75m &13d, for each group respectively.

InterventionParticipants (Count of Participants)
Treatment Assignment Code 1 (TAC1)13
TAC1 -> TAC41
TAC29
TAC2 -> TAC11
TAC2 -> TAC31
TAC322
TAC3 -> TAC12
TAC3 -> TAC1 -> TAC41
TAC3 -> TAC42
TAC415
TAC4 -> TAC17
TAC4 -> TAC21
TAC4 -> TAC32
Participants Enrolled But Not Treated2

[back to top]

Proportion of Participants With 4 Month Progression-free Survival (PFS)

Time from random assignment to progression or death from any cause (whichever comes first). Progression was measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Progression is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. And the appearance of one or more new lesions is also considered progressions. (NCT01827384)
Timeframe: 4 months

Interventionproportion of participants (Number)
Treatment Assignment Code 1 (TAC1)0.23
TAC1 -> TAC40.00
TAC20.22
TAC2 -> TAC10.00
TAC2 -> TAC31.00
TAC30.41
TAC3 -> TAC10.50
TAC3 -> TAC1 -> TAC40.00
TAC3 -> TAC40.00
TAC40.13
TAC4 -> TAC10.29
TAC4 -> TAC20.00
TAC4 -> TAC30.00

[back to top]

Progression Free Survival (PFS) by Blinded Independent Review Committee (BIRC)

PFS defined as time from date of randomization to date of first documented disease (as assessed by Blinded Independent Review Committee (BIRC) per RECIST 1.1) or date of death due to any cause (NCT01828099)
Timeframe: from the date of randomization to the date of first radiologically documented disease progression or death due to any cause (assessed every 6 weeks up to approximately 34 months)

Interventionmonths (Median)
Ceritinib16.6
Chemotherapy8.1

[back to top]

Comparison of the Objective Response Rate Between the Two Treatment Groups p

Objective response rate is defined as the percentage of subjects who achieve best overall response of irCR or irPR pr irRECIST and evaluated by independent radiology.. (NCT01836029)
Timeframe: From the time of randomization until the best response on treatment is documented.

Interventionpercentage of participants (Number)
Chemotherapy and Cetuximab Plus VTX-233738.0
Chemotherapy and Cetuximab Plus Placebo33.7

[back to top]

Comparison of Overall Survival (OS) Between the 2 Treatment Groups.

Estimated using Kaplan-Meier product limit estimates, 1-sided stratified log-rank test, and Cox proportional hazard model; all with 90% 1-sided confidence intervals. (NCT01836029)
Timeframe: OS is the time from randomization until death due to any cause or the date last confirmed to be alive.

Interventiondays (Median)
Chemotherapy and Cetuximab Plus VTX-2337412
Chemotherapy and Cetuximab Plus Placebo343

[back to top]

Comparison of Progression Free Survival (PFS) Between Treatment Groups Using irRECIST and Evaluated by Independent Radiology.

PFS was based on central assessment by a blinded independent radiologist per immune related response evaluation criteria for solid tumors (irRECIST) and was summarized and displayed by treatment arm using Kaplan-Meier methods. Treatments were compared using a stratified log-rank test controlling for randomization stratification factors. The hazard ratio between the 2 treatment arms, as well as the associated one-sided 90% CI and p-value, were presented using a Cox proportional hazards regression model. (NCT01836029)
Timeframe: PFS is the time from randomization until disease progression or death, whichever comes first.

Interventiondays (Median)
Chemotherapy and Cetuximab Plus VTX-2337185
Chemotherapy and Cetuximab Plus Placebo181

[back to top]

Comparison of Adverse Events (AEs) Between the Two Treatment Groups.

The frequency and severity of adverse events, including any clinically significant changes in physical exam, laboratory values, or other clinical assessment. (NCT01836029)
Timeframe: AEs were collected from the first dose of study drug given on Cycle 1 Day 1 until 7 days after the dose of study drug or End of Treatment visit, whichever occurred first. Overall mean duration of exposure was 25.3 weeks.

,
Interventionpercentage of participants (Number)
Subjects with TEAESubjects with Grade 3 and above TEAESubjects with serious TEAESubjects with TEAE with outcome of deathSubjects discontinued treatment due to TEAE
Chemotherapy and Cetuximab Plus Placebo10083.739.58.118.6
Chemotherapy and Cetuximab Plus VTX-233710084.339.34.519.1

[back to top]

Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E

Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 1 was planned for Parts A, B, C, D, and E. (NCT01840579)
Timeframe: At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days)

Interventiondays (Median)
Part A: Pembrolizumab 2 mg/kg0.223
Part A: Pembrolizumab 10 mg/kg0.00903
Part B: Pembrolizumab+Cisplatin/Pemetrexed1.98
Part B: Pembrolizumab+Carboplatin/Pemetrexed2.52
Part C: Pembrolizumab+Carboplatin/Paclitaxel0.028
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel0.027
Part D: Pembrolizumab+Ipilimumab0.026
Part E: Pembrolizumab+Cisplatin/Etoposide0.026
Part E: Pembrolizumab+Carboplatin/Etoposide0.028
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF0.031

[back to top]

Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 4: Part D

Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle length for Part D was 42 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 4 was only planned for Part D. (NCT01840579)
Timeframe: Cycle 4 Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose

Interventiondays (Median)
Part D: Pembrolizumab+Ipilimumab0.026

[back to top]

Time to Maximum Serum Concentration (Tmax) of Pembrolizumab for Cycle 8: Parts B, C, and E

Tmax was the time required to reach the maximum concentration of pembrolizumab in serum. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 for Parts B, C, and E was 21 days. Tmax is reported as median and full range. Per protocol, analysis for Tmax in Cycle 8was planned for Parts B, C, and E. (NCT01840579)
Timeframe: Cycle 8 Day 1 pre- and post-dose

Interventiondays (Median)
Part B: Pembrolizumab+Cisplatin/Pemetrexed0.024
Part B: Pembrolizumab+Carboplatin/Pemetrexed0.026
Part C: Pembrolizumab+Carboplatin/Paclitaxel0.028
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel0.027
Part E: Pembrolizumab+Cisplatin/Etoposide0.029
Part E: Pembrolizumab+Carboplatin/Etoposide0.026

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 1 Ctrough was taken for Parts A, B, C, D, and E on Day 1 of Cycle 2 at pre-dose (prior to Cycle 2 infusion). Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 1 Ctrough was planned for Parts A, B, C, D, and E. (NCT01840579)
Timeframe: Cycle 2 Day 1 pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg11.2
Part A: Pembrolizumab 10 mg/kg47.9
Part B: Pembrolizumab+Cisplatin/Pemetrexed19.88
Part B: Pembrolizumab+Carboplatin/Pemetrexed15.79
Part C: Pembrolizumab+Carboplatin/Paclitaxel9.45
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel10.96
Part D: Pembrolizumab+Ipilimumab8.26
Part E: Pembrolizumab+Cisplatin/Etoposide14.57
Part E: Pembrolizumab+Carboplatin/Etoposide15.30
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF17.88

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 10: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 10 Ctrough was taken for Part D on Day 22 of Cycle 10 at pre-dose (prior to Cycle 11 infusion). Cycle 10 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 10 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 10 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab36.30

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 12: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 12 Ctrough was taken for Part D on Day 22 of Cycle 12 at pre-dose (prior to Cycle 13 infusion). Cycle 12 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 12 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 12 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab30.90

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 14: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 14 Ctrough was taken for Part D on Day 22 of Cycle 14 at pre-dose (prior to Cycle 15 infusion). Cycle 14 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 14 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 14 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab28.40

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 15: Parts A, B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts A, B, C, and E on Day 1 of Cycle 16 at pre-dose (prior to Cycle 16 infusion). Cycle 15 length for Part A was 14 days. Cycle 15 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 15 Ctrough was only planned for Parts A, B, C, and E. (NCT01840579)
Timeframe: Cycle 16 Day 1 pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg199
Part B: Pembrolizumab+Cisplatin/Pemetrexed47.50
Part B: Pembrolizumab+Carboplatin/Pemetrexed56.27
Part E: Pembrolizumab+Cisplatin/Etoposide52.50

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 16: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 16 Ctrough was taken for Part D on Day 22 of Cycle 16 at pre-dose (prior to Cycle 17 infusion). Cycle 16 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 16 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 16 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab30.70

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 17: Part A

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose (prior to Cycle 18 infusion). Cycle 17 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 17 Ctrough was planned for Part A. (NCT01840579)
Timeframe: Cycle 18 Day 1 pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg125

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 4: Parts A and D

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 4 at pre-dose and 0-30 minutes post-dose and for Part D on Day 22 of Cycle 4 at pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and 0-30 minutes post-dose. Cycle 4 length for Part A was 14 days. Cycle 4 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 4 was only planned for Parts A and D. (NCT01840579)
Timeframe: Cycle 4 Day 1 pre- and post-dose (Part A) and Day 22 pre-dose (Day 1 of the following cycle prior to pembrolizumab infusion) and post-dose (Part D)

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg93.0
Part A: Pembrolizumab 10 mg/kg367
Part D: Pembrolizumab+Ipilimumab86.21

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 2: Part A

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 2 at pre-dose and 0-30 minutes post-dose. Cycle 2 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 2 was only planned for Part A. (NCT01840579)
Timeframe: Cycle 2 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg82.7
Part A: Pembrolizumab 10 mg/kg322

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 18: Part A

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 18 at pre-dose and 0-30 minutes post-dose. Cycle 18 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 18 was only planned for Part A. (NCT01840579)
Timeframe: Cycle 18 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg329

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 16: Part A

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 16 at pre-dose and 0-30 minutes post-dose. Cycle 16 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 16 was only planned for Part A. (NCT01840579)
Timeframe: Cycle 16 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg348

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 14: Part A

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 14 at pre-dose and 0-30 minutes post-dose. Cycle 14 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 14 was only planned for Part A. (NCT01840579)
Timeframe: Cycle 14 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg335

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 12: Part A

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 12 at pre-dose and 0-30 minutes post-dose. Cycle 12 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 12 was only planned for Part A. (NCT01840579)
Timeframe: Cycle 12 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg357

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 10: Part A

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 10 at pre-dose and 0-30 minutes post-dose. Cycle 10 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 10 was only planned for Part A. (NCT01840579)
Timeframe: Cycle 10 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg133
Part A: Pembrolizumab 10 mg/kg266

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 1: Parts A, B, C, D, and E

Cmax was the maximum observed concentration of pembrolizumab in serum. For Part A, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), 6 hour (hr) (±30 min), and 24hr; Days 2, 3, 8, 15, and 22 (±2 hr for Day 2 to Day 22) after completion of infusion. For Parts B, C, and E, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), and Day 15 (±24 hr) after completion of infusion. For Part D, samples were collected on Day 1 at pre-dose, post-dose (to +30 min), and 24hr; Day 5 (96hr was preferred, 72hr or 120hr were also acceptable, ±2 hr), Day 15, and Day 22 (±24 hr) after completion of infusion. Cycle 1 length for Part A was 28 days. Cycle 1 length for Parts B, C, and E was 21 days. Cycle 1 length for Part D was 42 days. Cmax is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Cmax was planned for Parts A, B, C, D, and E. (NCT01840579)
Timeframe: At designated timepoints in Cycle 1 for Parts A, B, C, D, and E (up to approximately 22 days)

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg47.4
Part A: Pembrolizumab 10 mg/kg250
Part B: Pembrolizumab+Cisplatin/Pemetrexed52.51
Part B: Pembrolizumab+Carboplatin/Pemetrexed47.46
Part C: Pembrolizumab+Carboplatin/Paclitaxel56.39
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel53.79
Part D: Pembrolizumab+Ipilimumab72.71
Part E: Pembrolizumab+Cisplatin/Etoposide74.33
Part E: Pembrolizumab+Carboplatin/Etoposide84.55
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF88.65

[back to top]

Clearance (CL) of Pembrolizumab Over Time for Part A Cycle 1

CL was the volume of plasma from which pembrolizumab was eliminated per unit time. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. CL is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for CL was only planned for Part A Cycle 1. (NCT01840579)
Timeframe: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

InterventionmL/day/kg (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg2.46
Part A: Pembrolizumab 10 mg/kg2.93

[back to top]

Area Under the Concentration Time Curve From 0-Infinity (AUC 0-inf) for Part A Cycle 1

AUC 0-inf was the AUC of pembrolizumab from time zero to infinity after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-inf is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-inf was only planned for Part A Cycle 1. (NCT01840579)
Timeframe: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

Interventionµg•day/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg812
Part A: Pembrolizumab 10 mg/kg3410

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 19: Parts B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 20 at pre-dose (prior to Cycle 20 infusion). Cycle 19 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 19 Ctrough was only planned for Parts B, C, and E. (NCT01840579)
Timeframe: Cycle 20 Day 1 Pre-dose

Interventionµg/mL (Geometric Mean)
Part B: Pembrolizumab+Cisplatin/Pemetrexed48.50
Part B: Pembrolizumab+Carboplatin/Pemetrexed50.98

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 2: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 2 Ctrough was taken for Part D on Day 22 of Cycle 2 at pre-dose (prior to Cycle 3 infusion). Cycle 2 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 2 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 2 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab20.10

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 23: Parts B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 24 at pre-dose (prior to Cycle 24 infusion). Cycle 23 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 23 Ctrough was only planned for Parts B, C, and E. (NCT01840579)
Timeframe: Cycle 24 Day 1 Pre-dose

Interventionµg/mL (Geometric Mean)
Part B: Pembrolizumab+Cisplatin/Pemetrexed42.40
Part B: Pembrolizumab+Carboplatin/Pemetrexed51.72

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 27: Parts B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling was taken for Parts B, C, and E on Day 1 of Cycle 28 at pre-dose (prior to Cycle 28 infusion). Cycle 27 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 27 Ctrough was only planned for Parts B, C, and E. (NCT01840579)
Timeframe: Cycle 28 Day 1 Pre-dose

Interventionµg/mL (Geometric Mean)
Part B: Pembrolizumab+Cisplatin/Pemetrexed53.90
Part B: Pembrolizumab+Carboplatin/Pemetrexed68.20

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Part D on Day 22 of Cycle 3 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). (NCT01840579)
Timeframe: Cycle 3 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab30.30

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 3: Parts A, B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 3 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 4 at pre-dose (prior to Cycle 4 infusion). Cycle 3 length for Part A was 14 days. Cycle 3 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). (NCT01840579)
Timeframe: Cycle 4 Day 1 at Pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg37.2
Part A: Pembrolizumab 10 mg/kg83.0
Part B: Pembrolizumab+Cisplatin/Pemetrexed32.71
Part B: Pembrolizumab+Carboplatin/Pemetrexed25.38
Part C: Pembrolizumab+Carboplatin/Paclitaxel24.80
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel23.63
Part E: Pembrolizumab+Cisplatin/Etoposide32.20
Part E: Pembrolizumab+Carboplatin/Etoposide30.43
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF34.31

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 4: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 4 Ctrough was taken for Part D on Day 22 of Cycle 4 at pre-dose (prior to Cycle 5 infusion). Cycle 4 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 4 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 4 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab28.08

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 5: Parts A, B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 5 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 6 at pre-dose (prior to Cycle 6 infusion). Cycle 5 length for Part A was 14 days. Cycle 5 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 5 Ctrough was only planned for Parts A, B, C, and E. (NCT01840579)
Timeframe: Cycle 6 Day 1 pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg46.5
Part A: Pembrolizumab 10 mg/kg38.3
Part B: Pembrolizumab+Cisplatin/Pemetrexed37.70
Part B: Pembrolizumab+Carboplatin/Pemetrexed23.84
Part C: Pembrolizumab+Carboplatin/Paclitaxel35.33
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel33.91
Part E: Pembrolizumab+Cisplatin/Etoposide47.82
Part E: Pembrolizumab+Carboplatin/Etoposide38.63
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF46.47

[back to top]

Volume of Distribution (Vz) of Pembrolizumab Over Time for Part A Cycle 1

Vz was the volume of distribution during the terminal phase. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 prior to pembrolizumab infusion. Cycle 1 length A was 28 days. Vz is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for Vz was only planned for Part A Cycle 1. (NCT01840579)
Timeframe: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

InterventionmL/kg (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg65.3
Part A: Pembrolizumab 10 mg/kg76.5

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 6: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 6 Ctrough was taken for Part D on Day 22 of Cycle 6 at pre-dose (prior to Cycle 7 infusion). Cycle 6 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 6 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 6 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab40.10

[back to top]

Area Under the Concentration Time Curve From 0-28 Days (AUC 0-28) for Part A Cycle 1

AUC 0-28 was the AUC of pembrolizumab from time zero to 28 days after dosing. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and Day 1 of Cycle 2 pre-dose. Cycle 1 length was 28 days. AUC 0-28 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for AUC 0-28 was only planned for Part A Cycle 1. (NCT01840579)
Timeframe: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

Interventionµg•day/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg507
Part A: Pembrolizumab 10 mg/kg2219

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 7: Parts A, B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 7 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 8 at pre-dose (prior to Cycle 8 infusion). Cycle 7 length for Part A was 14 days. Cycle 7 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 7 Ctrough was only planned for Parts A, B, C, and E. (NCT01840579)
Timeframe: Cycle 8 Day 1 pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg54.9
Part A: Pembrolizumab 10 mg/kg134
Part B: Pembrolizumab+Cisplatin/Pemetrexed39.33
Part B: Pembrolizumab+Carboplatin/Pemetrexed37.44
Part C: Pembrolizumab+Carboplatin/Paclitaxel42.70
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel32.44
Part E: Pembrolizumab+Cisplatin/Etoposide54.0
Part E: Pembrolizumab+Carboplatin/Etoposide48.92
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF43.10

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 8: Part D

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 8 Ctrough was taken for Part D on Day 22 of Cycle 8 at pre-dose (prior to Cycle 9 infusion). Cycle 8 length for Part D was 42 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 8 Ctrough was only planned for Part D. (NCT01840579)
Timeframe: Cycle 8 Day 22 pre-dose

Interventionµg/mL (Geometric Mean)
Part D: Pembrolizumab+Ipilimumab35.20

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 9: Part A

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 9 Ctrough was taken for Part A on Day 1 of Cycle 10 at pre-dose (prior to Cycle 10 infusion). Cycle 9 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 9 Ctrough was only planned for Part A. (NCT01840579)
Timeframe: Cycle 10 Day 1 pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg68.4
Part A: Pembrolizumab 10 mg/kg125

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 6: Part A

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Part A on Day 1 of Cycle 6 at pre-dose and 0-30 minutes post-dose. Cycle 6 length for Part A was 14 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 6 was only planned for Part A. (NCT01840579)
Timeframe: Cycle 6 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg115
Part A: Pembrolizumab 10 mg/kg286

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 13: Part A

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 13 Ctrough was taken for Part A on Day 1 of Cycle 14 at pre-dose (prior to Cycle 14 infusion). Cycle 13 length for Part A was 14 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 13 Ctrough was only planned for Part A. (NCT01840579)
Timeframe: Cycle 14 Day 1 pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg147

[back to top]

Maximum Serum Concentration (Cmax) of Pembrolizumab for Cycle 8: Parts A, B, C, and E

Cmax was the maximum observed concentration of pembrolizumab in serum. Blood sampling was taken for Parts A, B, C and E on Day 1 of Cycle 8 at pre-dose and 0-30 minutes post-dose. Cycle 8 length for Part A was 14 days. Cycle 8 length for Parts B, C, and E was 21 days. Cmax is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cmax in Cycle 8 was only planned for Parts A, B, C, and E. (NCT01840579)
Timeframe: Cycle 8 Day 1 pre- and post-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg115
Part A: Pembrolizumab 10 mg/kg298
Part B: Pembrolizumab+Cisplatin/Pemetrexed124.47
Part B: Pembrolizumab+Carboplatin/Pemetrexed95.51
Part C: Pembrolizumab+Carboplatin/Paclitaxel122.00
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel66.62
Part E: Pembrolizumab+Cisplatin/Etoposide150.00
Part E: Pembrolizumab+Carboplatin/Etoposide131.78

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab for Cycle 11: Parts A, B, C, and E

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose. Blood sampling for Cycle 11 Ctrough was taken for Parts A, B, C, and E on Day 1 of Cycle 12 at pre-dose (prior to Cycle 12 infusion). Cycle 11 length for Part A was 14 days. Cycle 11 length for Parts B, C, and E was 21 days. Ctrough is reported as geometric mean with a percent coefficient of variation (%CV). Per protocol, analysis for Cycle 11 Ctrough was only planned for Parts A, B, C, and E. (NCT01840579)
Timeframe: Cycle 12 Day 1 Pre-dose

Interventionµg/mL (Geometric Mean)
Part A: Pembrolizumab 10 mg/kg159
Part B: Pembrolizumab+Cisplatin/Pemetrexed39.30
Part B: Pembrolizumab+Carboplatin/Pemetrexed45.00
Part C: Pembrolizumab+Carboplatin/Paclitaxel32.60
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel57.80
Part E: Pembrolizumab+Cisplatin/Etoposide52.20

[back to top]

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT01840579)
Timeframe: Up to approximately 37.9 months

InterventionParticipants (Count of Participants)
Part A: Pembrolizumab 2 mg/kg0
Part A: Pembrolizumab 10 mg/kg0
Part B: Pembrolizumab+Cisplatin/Pemetrexed1
Part B: Pembrolizumab+Carboplatin/Pemetrexed5
Part C: Pembrolizumab+Carboplatin/Paclitaxel4
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel3
Part D: Pembrolizumab+Ipilimumab2
Part E: Pembrolizumab+Cisplatin/Etoposide1
Part E: Pembrolizumab+Carboplatin/Etoposide1
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF0

[back to top]

Number of Participants Who Experienced at Least One Adverse Event (AE)

An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. (NCT01840579)
Timeframe: Up to approximately 51.3 months

InterventionParticipants (Count of Participants)
Part A: Pembrolizumab 2 mg/kg3
Part A: Pembrolizumab 10 mg/kg7
Part B: Pembrolizumab+Cisplatin/Pemetrexed6
Part B: Pembrolizumab+Carboplatin/Pemetrexed6
Part C: Pembrolizumab+Carboplatin/Paclitaxel8
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel6
Part D: Pembrolizumab+Ipilimumab5
Part E: Pembrolizumab+Cisplatin/Etoposide6
Part E: Pembrolizumab+Carboplatin/Etoposide6
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF3

[back to top]

Number of Participants Who Experienced Dose-limiting Toxicities (DLTs)

"The following toxicities graded per the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0) were considered DLTs if judged by the investigator to be related to either study drug:~Grade (G) 4 neutropenia lasting >7 days~Grade 3 and Grade 4 febrile neutropenia~Grade 4 thrombocytopenia (<25,000/mm^3)~Grade 4 anemia~Grade 4 non-hematologic toxicity (not laboratory)~Grade 3 non-hematologic toxicity (not laboratory) lasting >3 days despite optimal supportive care~Any Grade 3 non-hematologic laboratory value if medical intervention is required to treat the participant or the abnormality persists for >7 days.~(Part D only) Missing the second dose of pembrolizumab (Cycle1 Day 22) due to drug-related adverse event" (NCT01840579)
Timeframe: Cycle 1 (first dose and up to 4 weeks in Part A, 3 weeks in Parts B, C, E, and 6 weeks in Part D)

InterventionParticipants (Count of Participants)
Part A: Pembrolizumab 2 mg/kg0
Part A: Pembrolizumab 10 mg/kg0
Part B: Pembrolizumab+Cisplatin/Pemetrexed1
Part B: Pembrolizumab+Carboplatin/Pemetrexed0
Part C: Pembrolizumab+Carboplatin/Paclitaxel2
Part C: Pembrolizumab+Carboplatin/Nab-paclitaxel0
Part D: Pembrolizumab+Ipilimumab0
Part E: Pembrolizumab+Cisplatin/Etoposide3
Part E: Pembrolizumab+Carboplatin/Etoposide0
Part E: Pembrolizumab+Cisplatin/Etoposide+G-CSF0

[back to top]

Terminal Half-Life (t1/2) of Pembrolizumab Over Time for Part A Cycle 1

t1/2 was the time required to divide the pembrolizumab concentration by two after reaching pseudo-equilibrium. Blood sampling was taken at the following timepoints: Part A Cycle 1 Day 1 at pre-dose, 0-30 minutes post-dose, and at 6, 24, 48, 168, 336, 504 hours after completion of pembrolizumab infusion and pre-dose Day 1 of the following cycle prior to pembrolizumab infusion. Cycle 1 length A was 28 days. t1/2 is reported as geometric mean with a percent coefficient of variation. Per protocol, analysis for t1/2 was only planned for Part A Cycle 1. (NCT01840579)
Timeframe: At designated timepoints in Cycle 1 for Part A (Up to approximately 28 days)

Interventiondays (Geometric Mean)
Part A: Pembrolizumab 2 mg/kg18.4
Part A: Pembrolizumab 10 mg/kg18.1

[back to top]

Phase 1b: To Determine the Maximum Tolerated Dose (MTD) of OMP-59R5 When Administered With Etoposide and Cisplatin or Carboplatin (Number of Subjects With DLTs)

To determine the MTD of tarextumab when administered on Day 1 of each 21 day cycle along with etoposide 100 mg/m2 on Days 1, 2 and 3, and cisplatin 80 mg/m2 or carboplatin area under the curve (AUC) of 5 mg/mL•min on Day 1 in subjects with untreated extensive stage small cell lung cancer. DLT evaluable population includes all subjects who received at least 1 partial dose of OMP-59R5 during the Phase 1b dose escalation portion of the study including the carboplatin cohort and who had completed Day 21 cycle of 1 OMP-59R5 administration or had discontinued due to drug-related toxicity. (NCT01859741)
Timeframe: Up to 1 year in absence of unacceptable toxicity or disease progression.

InterventionParticipants (Count of Participants)
P1B: OMP-59R5 5mg/kg + ETO + CIS0
P1B: OMP-59R5 7.5 mg/kg + ETO + CIS0
P1B: OMP-59R5 10 mg/kg + ETO + CIS1
P1B: OMP-59R5 12.5 mg/kg + ETO + CIS0
P1B: OMP-59R5 15 mg/kg + ETO + CIS0
P1B: OMP-59R5 15mg/kg + ETO + CARB0

[back to top]

Duration of Response

Duration of response: time from the date of first documented response per the investigator response assessment (CR or PR) to the date of PD or the date of last disease assessment if the participant discontinued the study before PD using RECIST 1.1 CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis <10 mm); no new lesions. PR: >=30% decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions. PD: at least a 20% increase (including an absolute increase of at least 5 mm) in sum of diameters of target lesions, taking as reference smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. (NCT01862328)
Timeframe: From the date of first documented response (CR or PR) to the date of first documented PD or the date of last disease assessment if the participants discontinued the study before PD (up to 5 years)

Interventionmonths (Mean)
Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^22.880
Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC62.270
Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC516.153
Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC57.015

[back to top]

Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924

(NCT01862328)
Timeframe: Cycle 1 Day 1 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2] and 28 days [Arm 3])

,,,,,
Interventionnanogram per milliliter (ng/ml) (Mean)
Cycle 1 Day 1: End-doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 3 hours post doseCycle 1 Day 1: 20 hours post dose
Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2163.882.048.07.5
Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2197.1130.695.814.6
Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5275.7156.8152.423.4
Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5257.3192.7138.034.6
Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5372.7246.7186.924.4
Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2222.0160.5103.014.2

[back to top]

MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924

The number of participants analyzed includes only those participants who had data available for this measure. (NCT01862328)
Timeframe: Cycle 1 Days 1 and 5 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2])

Interventionng/ml (Mean)
Cycle 1 Day 1: End-doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 3 hours post doseCycle 1 Day 1: 6 hours post doseCycle 1 Day 1: 20 hours post doseCycle 1 Day 5: End-doseCycle 1 Day 5: 1.5 hours post doseCycle 1 Day 5: 3 hours post doseCycle 1 Day 5: 6 hours post doseCycle 1 Day 5: 20 hours post dose
Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5429.8253.6192.8136.330.2253.2171.0118.476.510.9

[back to top]

MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924

The number of participants analyzed includes only those participants who had data available for this measure. (NCT01862328)
Timeframe: Cycle 1 Days 1 and 5 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2])

Interventionng/ml (Mean)
Cycle 1 Day 1: End-doseCycle 1 Day 1: 1.5 hours post doseCycle 1 Day 1: 3 hours post doseCycle 1 Day 1: 7 hours post doseCycle 1 Day 1: 20 hours post doseCycle 1 Day 5: End-doseCycle 1 Day 5: 1.5 hours post doseCycle 1 Day 5: 3 hours post doseCycle 1 Day 5: 7 hours post doseCycle 1 Day 5: 20 hours post dose
Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2152.8137.386.463.414.2211.1115.396.738.39.8

[back to top]

Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

(NCT01862328)
Timeframe: Baseline up to 30 days after the last dose of study drug (up to 5 years)

,,,,,,
InterventionParticipants (Count of Participants)
TEAESAE
Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^241
Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2189
Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC572
Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5123
Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC571
Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC663
Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2107

[back to top] [back to top] [back to top]

Percentage of Participants With Objective Response

Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease; all nodes, both target and non-target, must decrease to normal (short axis less than [<] 10 millimeter [mm]); no new lesions. PR: greater than or equal to (>=) 30 percent (%) decrease under baseline of sum of diameters of all target lesions; short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions; no unequivocal progression of non-target disease; no new lesions. (NCT01862328)
Timeframe: Screening, Cycle 2 Days 15 (Arm 1, 2a, and 2) and 22 (Arm 3) then every other Cycle thereafter up to 30 days after the last dose of study drug (up to 5 years) (Cycle Length = 21 days [Arm 1, 2a, and 2] and 28 days [Arm 3])

,,,,,,
Interventionpercentage of participants (Number)
CRPR
Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^200
Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2019
Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC500
Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC51836
Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5040
Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6017
Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^200

[back to top]

Number of Alive Subjects

Survival status of patients after treatment will be determined. (NCT01867086)
Timeframe: 24 months

InterventionParticipants (Count of Participants)
Alive Subjects After 24 monthsDead Subjects After 24 months
Vigil™ Vaccine01

[back to top]

Immune Analysis in Blood

To determine if subjects will have a positive (defined as >10 ELISPOTS from baseline) immune response to Vigil. Blood was collected to compare ELISPOT results from baseline until 30 days after last dose. (NCT01867086)
Timeframe: Baseline, End of Treatment (30 days after last dose) up to 12 months

InterventionParticipants (Count of Participants)
ELISPOT-Positive After 12 monthsELISPOT-Negative After 12 months
Vigil™ Vaccine10

[back to top]

Number of Participants With the Abnormal Urinalysis Findings

Urinalysis parameters included urine protein, urine glucose, urine ketones and occult blood were assessed. Dipstick test was performed for routine urinalysis. Abnormal values such as trace, 1+, 2+, 3+, 4+, >1000, >=1000, and >10 have been reported. (NCT01868022)
Timeframe: Up to Cycle 16 (each cycle was of 21 days)

,,,,,,,,
InterventionParticipants (Count of Participants)
Cycle 1 Day 1, Urine glucose, >1000Cycle 1 Day 1, Urine glucose, 2+Cycle 1 Day 1, Urine glucose, traceCycle 2 Day 1, Urine glucose, traceCycle 4 Day 1, Urine glucose, >=1000Cycle 4 Day 1, Urine glucose, 4+Cycle 1 Day 1, Urine ketones, traceCycle 4 Day 1, Urine ketones, traceCycle 28, Day 1, Urine ketones, traceCycle 1 Day 1, Occult Blood, 1+Cycle 1 Day 1, Occult Blood, 3+Cycle 2 Day 1, Occult Blood, 1+Cycle 2 Day 1, Occult Blood, traceCycle 4 Day 1, Occult Blood, traceCycle 4 Day 1, Occult Blood, 1+Cycle 4 Day 1, Occult Blood, 2+Cycle 8 Day 1, Occult Blood, 1+Cycle 1 Day 1, Urine protein, 1+Cycle 1 Day 1, Urine protein, traceCycle 2, Day 1, Urine protein, traceCycle 2, Day 1, Urine protein, 2+Cycle 4, Day 1, Urine protein, traceCycle 8, Day 1, Urine protein, traceCycle 12, Day 1, Urine protein, traceCycle 16, Day 1, Urine protein, trace
10 mg/kg GSK3052230 + Docetaxel: Arm B0000000000000000001100000
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0000000000000000001000001
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0000000000000000000000000
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0000001000110001101002310
20 mg/kg GSK3052230 + Docetaxel: Arm B0000000000000000000000000
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A1000101102000000012100000
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0011012011011100020111000
5 mg/kg GSK3052230 + Docetaxel: Arm B0100000000000000000000000
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0000000000000100000000000

[back to top]

Number of Participants With Maximum Tolerated Dose (MTD) or Maximum Feasible Dose (MFD)

The MTD is defined as the highest dose level tested at which < 33 percent of participants experience a DLT. In cases when MTD is not reached dose was described as the MFD. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionParticipants (Count of Participants)
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A14
20 mg/kg GSK3052230 + Docetaxel: Arm B3
15 mg/kg GSK3052230 + Pemetrexed + Carboplatin: Arm C25

[back to top]

Number of Participants With Hematology Change From Baseline With Respect to the Normal Range

Hematology parameters included platelet Count, red blood cell (RBC) Count, hemoglobin, absolute white blood cell (WBC) Count, absolute neutrophils (Neu), absolute lymphocytes (Lym), absolute monocytes (Mono), absolute eosinophils (Eos), absolute basophils (Baso). Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Hematology parameters with worst-case change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). (NCT01868022)
Timeframe: Median of 28.5 weeks

,,,,,,,,
InterventionParticipants (Count of Participants)
Baso, decrease to low, n=3,3,14,3,3,3,3,22,8Baso, normal or no change, n=3,3,14,3,3,3,3,22,8Baso, increase to high, n=3,3,14,3,3,3,3,22,8Eos, decrease to low, n=3,3,14,3,3,3,3,24,8Eos, normal or no change, n=3,3,14,3,3,3,3,24,8Eos, increase to high, n=3,3,14,3,3,3,3,24,8Mono, decrease to low, n=3,3,14,3,3,3,3,25,8Mono, normal or no change, n=3,3,14,3,3,3,3,25,8Mono, increase to high, n=3,3,14,3,3,3,3,25,8RBC, decrease to low, n=3,3,14,3,3,3,3,25,8RBC, normal or no change, n=3,3,14,3,3,3,3,25,8RBC, increase to high, n=3,3,14,3,3,3,3,25,8
10 mg/kg GSK3052230 + Docetaxel: Arm B111130203121
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A030030203210
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C030030220120
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C51348145612101793
20 mg/kg GSK3052230 + Docetaxel: Arm B030030102210
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A194111211451041
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C161351335341
5 mg/kg GSK3052230 + Docetaxel: Arm B030030021030
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A030030310300

[back to top]

Number of Participants With Clinically Significant Findings for 12-lead Electrocardiogram (ECG)

A single 12-lead ECG was performed at the specified timepoints during the study where the participant was instructed to be in semi-recumbent position for 5 minutes before obtaining the ECG. An ECG machine that automatically calculated the heart rate and measures like the PR, QRS, QT, and corrected QT intervals. Number of participants with worst-case post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported. (NCT01868022)
Timeframe: Median of 28.5 weeks

,,,,,,,,
InterventionParticipants (Count of Participants)
Abnormal not clinically significantAbnormal clinically significant
10 mg/kg GSK3052230 + Docetaxel: Arm B20
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A20
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C10
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C123
20 mg/kg GSK3052230 + Docetaxel: Arm B30
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A81
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C23
5 mg/kg GSK3052230 + Docetaxel: Arm B20
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A00

[back to top]

Number of Participants With Dose Delays

Dose reduction and delays were done due to toxicity, or in the interest of participant's safety per investigator discretion. Requirement for more than 2 dose reductions resulted in permanent discontinuation of chemotherapy. Participants with dose delay has been reported. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionParticipants (Count of Participants)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A2
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A4
5 mg/kg GSK3052230 + Docetaxel: Arm B2
10 mg/kg GSK3052230 + Docetaxel: Arm B1
20 mg/kg GSK3052230 + Docetaxel: Arm B0
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C2
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C12
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C1

[back to top]

Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range

Clinical chemistry parameters included potassium, sodium, chloride (Cl), total carbon dioxide (CO2), total and ionized calcium, magnesium, phosphate, albumin, glucose (fasting), Blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, Total bilirubin (T. Bil), and Direct bilirubin (D. Bil), total T3 and T4, free T4, amylase, lipase, prothrombin time, partial thromboplastin time, international normalized ratio, and fibrinogen. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Clinical chemistry parameters with change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). (NCT01868022)
Timeframe: Median of 28.5 weeks

,,
InterventionParticipants (Count of Participants)
D.Bil, decrease to low, n=2,2,8,1,2,2,1,12,6D.Bil, normal or no change, n=2,2,8,1,2,2,1,12,6D.Bil, increase to high, n=2,2,8,1,2,2,1,12,6Cl, decrease to low, n=3,3,14,3,3,3,3,25,8Cl, normal or no change, n=3,3,14,3,3,3,3,25,8Cl, increase to high, n=3,3,14,3,3,3,3,25,8CO2, decrease to low, n=3,3,14,3,3,3,3,25,8CO2, normal or no change, n=3,3,14,3,3,3,3,25,8CO2, increase to high, n=3,3,14,3,3,3,3,25,8Cr CL, decrease to low, n=3,3,9,2,1,3,3,15,4Cr CL, normal or no change, n=3,3,9,2,1,3,3,15,4Cr CL, increase to high, n=3,3,9,2,1,3,3,15,4Urea/BUN, decrease to low, n=3,2,13,3,2,3,3,25,8Urea/BUN,normal or no change,n=3,2,13,3,2,3,3,25,8Urea/BUN, increase to high, n=3,2,13,3,2,3,3,25,8
20 mg/kg GSK3052230 + Docetaxel: Arm B110120012030021
5 mg/kg GSK3052230 + Docetaxel: Arm B010030120011111
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A020120021120120

[back to top]

Number of Participants With Best Response

Best response defined as complete response (CR:disappearance of all target. Any pathological lymph nodes < 10 millimeter [mm] in the short axis) or partial response (PR at least a 30 percent decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters), stable disease (SD neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) or progressive disease (PR at least a 20 percent increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started. In addition, the sum must have an absolute increase from nadir of 5 mm) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST. Best response as per RECIST version 1.1 for Arm A and B participants has been reported. Best response according to RECIST version 1.1 or modified RECIST for Arm C participants has been reported. (NCT01868022)
Timeframe: Median of 28.5 weeks

,,,,,,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable disease, discontinuedStable disease, ongoingProgressive disease
10 mg/kg GSK3052230 + Docetaxel: Arm B00200
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A02100
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C02100
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0111021
20 mg/kg GSK3052230 + Docetaxel: Arm B00200
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A06502
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C01201
5 mg/kg GSK3052230 + Docetaxel: Arm B00201
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A01101

[back to top]

Number of Participants With Abnormal Echocardiogram (ECHO) Findings

Echocardiography scans were obtained at given time points using an echocardiogram and the findings for left ventricular ejection fraction (LVEF) were obtained. LVEF values at end of treatment (EOT) were recorded as no change or any increase and any decrease values. Only those participants available at the specified time points were analyzed. (NCT01868022)
Timeframe: Median of 28.5 weeks

,,,,,
InterventionParticipants (Count of Participants)
No change or any increaseAny Decrease
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C23
20 mg/kg GSK3052230 + Docetaxel: Arm B11
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A11
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C20
5 mg/kg GSK3052230 + Docetaxel: Arm B01
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A01

[back to top]

Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

Blood pressure was measured in a semi-supine position after 5 minutes of rest. Blood pressure was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented. NA indicates that data were not available as standard deviation could not be calculated for a single participant. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). (NCT01868022)
Timeframe: Baseline and up to Median of 28.5 weeks

,,,,,,,,
InterventionMillimeters of mercury (mmHg) (Mean)
DBP, n=3, 2, 9, 3, 2, 2, 3, 21, 5SBP, n=3, 1, 13, 2, 2, 2, 3, 21, 4
10 mg/kg GSK3052230 + Docetaxel: Arm B6.017.5
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0.5-14.0
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C2.33.0
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C12.812.5
20 mg/kg GSK3052230 + Docetaxel: Arm B3.56.0
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A2.09.6
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C10.618.7
5 mg/kg GSK3052230 + Docetaxel: Arm B-0.610.5
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A6.3-12.3

[back to top]

Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range

Clinical chemistry parameters included potassium, sodium, chloride (Cl), total carbon dioxide (CO2), total and ionized calcium, magnesium, phosphate, albumin, glucose (fasting), Blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, Total bilirubin (T. Bil), and Direct bilirubin (D. Bil), total T3 and T4, free T4, amylase, lipase, prothrombin time, partial thromboplastin time, international normalized ratio, and fibrinogen. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Clinical chemistry parameters with change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). (NCT01868022)
Timeframe: Median of 28.5 weeks

,,
InterventionParticipants (Count of Participants)
D.Bil, decrease to low, n=2,2,8,1,2,2,1,12,6D.Bil, normal or no change, n=2,2,8,1,2,2,1,12,6D.Bil, increase to high, n=2,2,8,1,2,2,1,12,6Cl, decrease to low, n=3,3,14,3,3,3,3,25,8Cl, normal or no change, n=3,3,14,3,3,3,3,25,8Cl, increase to high, n=3,3,14,3,3,3,3,25,8CO2, decrease to low, n=3,3,14,3,3,3,3,25,8CO2, normal or no change, n=3,3,14,3,3,3,3,25,8CO2, increase to high, n=3,3,14,3,3,3,3,25,8Cr CL, decrease to low, n=3,3,9,2,1,3,3,15,4Cr CL, normal or no change, n=3,3,9,2,1,3,3,15,4Cr CL, increase to high, n=3,3,9,2,1,3,3,15,4T4 free, decrease to low, n=0,1,6,0,1,0,2,16,3T4 free, normal or no change,=0,1,6,0,1,0,2,16,3T4 free, increase to high, n=0,1,6,0,1,0,2,16,3Total T3, decrease to low, n=0,1,1,0,1,0,1,6,3Total T3, normal or no change, n=0,1,1,0,1,0,1,6,3Total T3, increase to high, n=0,1,1,0,1,0,1,6,3Urea/BUN, decrease to low, n=3,2,13,3,2,3,3,25,8Urea/BUN,normal or no change,n=3,2,13,3,2,3,3,25,8Urea/BUN, increase to high, n=3,2,13,3,2,3,3,25,8
10 mg/kg GSK3052230 + Docetaxel: Arm B020210030010010010020
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A011102112210010010020
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A071581386180150010085

[back to top]

Number of Participants With Clinical Chemistry Changes From Baseline With Respect to the Normal Range

Clinical chemistry parameters included potassium, sodium, chloride (Cl), total carbon dioxide (CO2), total and ionized calcium, magnesium, phosphate, albumin, glucose (fasting), Blood urea nitrogen (BUN), creatinine (Cr), uric acid, creatinine clearance, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatase, Total bilirubin (T. Bil), and Direct bilirubin (D. Bil), total T3 and T4, free T4, amylase, lipase, prothrombin time, partial thromboplastin time, international normalized ratio, and fibrinogen. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Clinical chemistry parameters with change from Baseline with respect to normal range only has been presented. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). (NCT01868022)
Timeframe: Median of 28.5 weeks

,,
InterventionParticipants (Count of Participants)
D.Bil, decrease to low, n=2,2,8,1,2,2,1,12,6D.Bil, normal or no change, n=2,2,8,1,2,2,1,12,6D.Bil, increase to high, n=2,2,8,1,2,2,1,12,6Cl, decrease to low, n=3,3,14,3,3,3,3,25,8Cl, normal or no change, n=3,3,14,3,3,3,3,25,8Cl, increase to high, n=3,3,14,3,3,3,3,25,8CO2, decrease to low, n=3,3,14,3,3,3,3,25,8CO2, normal or no change, n=3,3,14,3,3,3,3,25,8CO2, increase to high, n=3,3,14,3,3,3,3,25,8Cr CL, decrease to low, n=3,3,9,2,1,3,3,15,4Cr CL, normal or no change, n=3,3,9,2,1,3,3,15,4Cr CL, increase to high, n=3,3,9,2,1,3,3,15,4T4 free, decrease to low, n=0,1,6,0,1,0,2,16,3T4 free, normal or no change,=0,1,6,0,1,0,2,16,3T4 free, increase to high, n=0,1,6,0,1,0,2,16,3T4 total, decrease to low, n=0,0,0,0,0,0,1,4,1T4 total, normal or no change, n=0,0,0,0,0,0,1,4,1T4 total, increase to high, n=0,0,0,0,0,0,1,4,1Total T3, decrease to low, n=0,1,1,0,1,0,1,6,3Total T3, normal or no change, n=0,1,1,0,1,0,1,6,3Total T3, increase to high, n=0,1,1,0,1,0,1,6,3Urea/BUN, decrease to low, n=3,2,13,3,2,3,3,25,8Urea/BUN,normal or no change,n=3,2,13,3,2,3,3,25,8Urea/BUN, increase to high, n=3,2,13,3,2,3,3,25,8
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C010210120120020010010012
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C07591522177961112311232141110
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C051352053040120001210134

[back to top]

Number of Participants With Non-serious Adverse Events (AEs) and Serious AEs (SAEs)

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, protocol-specific events including drug-induced liver injury with hyperbilirubinaemia, any new primary cancers, cardiac toxicity including Left Ventricular Ejection Fraction (LVEF) changes or treatment emergent cardiac valve toxicity and treatment emergent acute anterior uveitis were categorized as SAE. Participants having non-serious AE or SAE were included in the analysis. The All Treated Subjects Population comprised of all participants who received at least one dose of study treatment. (NCT01868022)
Timeframe: Median of 28.5 weeks

,,,,,,,,
InterventionParticipants (Count of Participants)
Non-serious AEsSAEs
10 mg/kg GSK3052230 + Docetaxel: Arm B33
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A33
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C30
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C245
20 mg/kg GSK3052230 + Docetaxel: Arm B31
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A145
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C84
5 mg/kg GSK3052230 + Docetaxel: Arm B32
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A30

[back to top]

Number of Participants With Dose-Limiting Toxicities (DLT)

DLT is defined as toxicities due to GSK3052230 or due to the combination of GSK3052230 with chemotherapy within Cycle 1 (first 21 days of period on study) that are unlikely to be due to another cause, such as the known effects of cytotoxics chemotherapy alone, disease progression, or accident, and protocol-specified criteria. Clinically significant toxicities that persist or occur beyond Cycle 1 that the investigator and GlaxoSmithKline (GSK) medical monitor consider dose-limiting may also be designated a DLT for the purpose of establishing Maximum tolerated dose (MTD). Number of participants with DLTs has been reported. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionParticipants (Count of Participants)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
5 mg/kg GSK3052230 + Docetaxel: Arm B0
10 mg/kg GSK3052230 + Docetaxel: Arm B0
20 mg/kg GSK3052230 + Docetaxel: Arm B0
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C1
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C3

[back to top]

Number of Participants Withdrew Due to AEs

An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. The AEs leading to permanent discontinuation from the study has been reported. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionParticipants (Count of Participants)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
5 mg/kg GSK3052230 + Docetaxel: Arm B0
10 mg/kg GSK3052230 + Docetaxel: Arm B1
20 mg/kg GSK3052230 + Docetaxel: Arm B0
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C2
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C1
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C3

[back to top]

Change From Baseline in Forced Vital Capacity (FVC) in of Arm C Participants With Malignant Pleural Mesothelioma (MPM)

FVC is the total amount of air exhaled during the Forced Expiratory Volume test. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Assessment of FVC was done on Day 1 of every odd cycle for Arm C participants with MPM. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available as standard deviation could not be calculated for a single participant. (NCT01868022)
Timeframe: Up to 31 cycles (each cycle was of 21 days)

InterventionLiters (Mean)
Cycle 3,Day 1, n=3, 24, 4Cycle 4,Day 1, n=1, 4, 1Cycle 5,Day 1, n=1, 23, 3Cycle 6,Day 1, n=1, 5, 2Cycle 7,Day 1, n=1, 15, 2
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0.303-0.3400.2400.3100.530

[back to top]

Change From Baseline in Forced Vital Capacity (FVC) in of Arm C Participants With Malignant Pleural Mesothelioma (MPM)

FVC is the total amount of air exhaled during the Forced Expiratory Volume test. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Assessment of FVC was done on Day 1 of every odd cycle for Arm C participants with MPM. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available as standard deviation could not be calculated for a single participant. (NCT01868022)
Timeframe: Up to 31 cycles (each cycle was of 21 days)

InterventionLiters (Mean)
Cycle 3,Day 1, n=3, 24, 4Cycle 4,Day 1, n=1, 4, 1Cycle 5,Day 1, n=1, 23, 3Cycle 6,Day 1, n=1, 5, 2Cycle 7,Day 1, n=1, 15, 2Cycle 8,Day 1, n=0, 3, 1Cycle 9,Day 1, n=0, 15, 1Cycle 11,Day 1, n=0, 12, 2Cycle 12,Day 1, n=0, 2, 1Cycle 13,Day 1, n=0, 8, 2Cycle 14,Day 1, n=0, 3, 1Cycle 15,Day 1, n=0, 6, 1Cycle 17,Day 1, n=0, 4, 1Cycle 19,Day 1, n=0, 1, 1Cycle 21,Day 1, n=0, 1, 1Cycle 23,Day 1, n=0, 1, 1Cycle 25,Day 1, n=0, 0, 1Cycle 27,Day 1, n=0, 0, 1Cycle 31,Day 1, n=0, 0, 1
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0.1380.6000.5870.1100.5750.6401.1300.5100.5800.5550.910-0.0300.5600.6200.5600.5100.4300.2200.270

[back to top]

Change From Baseline in Forced Vital Capacity (FVC) in of Arm C Participants With Malignant Pleural Mesothelioma (MPM)

FVC is the total amount of air exhaled during the Forced Expiratory Volume test. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. Assessment of FVC was done on Day 1 of every odd cycle for Arm C participants with MPM. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates that data were not available as standard deviation could not be calculated for a single participant. (NCT01868022)
Timeframe: Up to 31 cycles (each cycle was of 21 days)

InterventionLiters (Mean)
Cycle 3,Day 1, n=3, 24, 4Cycle 4,Day 1, n=1, 4, 1Cycle 5,Day 1, n=1, 23, 3Cycle 6,Day 1, n=1, 5, 2Cycle 7,Day 1, n=1, 15, 2Cycle 8,Day 1, n=0, 3, 1Cycle 9,Day 1, n=0, 15, 1Cycle 10,Day 1, n=0, 3, 0Cycle 11,Day 1, n=0, 12, 2Cycle 12,Day 1, n=0, 2, 1Cycle 13,Day 1, n=0, 8, 2Cycle 14,Day 1, n=0, 3, 1Cycle 15,Day 1, n=0, 6, 1Cycle 17,Day 1, n=0, 4, 1Cycle 19,Day 1, n=0, 1, 1Cycle 21,Day 1, n=0, 1, 1Cycle 23,Day 1, n=0, 1, 1
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0.2800.4130.2380.4640.3990.2630.3530.0630.3470.2250.389-0.2070.2470.158-0.02-0.27-0.62

[back to top]

Treatment Duration With GSK3052230

The number of participants administered study treatment were summarized according to the duration of therapy. The extent of treatment exposure is calculated as the number of cycles administered. The duration of exposure to study treatment is calculated from first day to last day of treatment plus 1 day. Median and full range (minimum and maximum) has been reported. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionCycles (Median)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A7.0
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A15.0
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A8.0
5 mg/kg GSK3052230 + Docetaxel: Arm B6.0
10 mg/kg GSK3052230 + Docetaxel: Arm B4.0
20 mg/kg GSK3052230 + Docetaxel: Arm B6.0
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C6.0
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C11.0
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C3.0

[back to top]

Progression Free Survival (PFS) as Assessed by Investigator

PFS is defined as the interval between first dose of GSK3052230 and the earliest date of disease progression or death due to any cause by investigator assessment per RECIST 1.1 (for Arm A and B participants) or modified RECIST (for Arm C participants). For participants who do not progress or die, PFS was censored at the time of last radiological scan. Participants who discontinued study with no post-treatment tumor assessment were censored at date of first dose of study drug. Mean and 95 percent CI has been reported. NA indicates that data were not available as only 1 participant had event, other two censored therefore there is no confidence interval. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionMonths (Median)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A4.1
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm ANA
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A5.5
5 mg/kg GSK3052230 + Docetaxel: Arm B4.6
10 mg/kg GSK3052230 + Docetaxel: Arm B9.5
20 mg/kg GSK3052230 + Docetaxel: Arm B5.1
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C4.6
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C7.4
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C4.1

[back to top]

Number of Participants With Overall Response Rate (ORR)

Overall Response Rate (ORR) is defined as the percentage of participants achieving a confirmed Complete response (CR) or Partial response (PR) from the start of treatment until disease progression as per RECIST version 1.1 or modified RECIST for participants in Arm C. This was determined based on Investigator assessments of response. 95% confidence intervals (CI) are calculated based on the unconditional exact method. ORR as per RECIST vesrion 1.1 for Arm A and B has been reported. ORR as per RECIST version 1.1 and modified RECIST version 1.1 for Arm C has been reported. The study population used for decision-making at the interim analyses during the dose expansion cohorts of the study arms is termed as the All Evaluable Participants Population. NA indicates 0 participants met ORR criteria therefore no dispersion. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionParticipants (Count of Participants)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A1
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A2
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A6
5 mg/kg GSK3052230 + Docetaxel: Arm B0
10 mg/kg GSK3052230 + Docetaxel: Arm B0
20 mg/kg GSK3052230 + Docetaxel: Arm B0
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C2
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C11
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C1

[back to top]

Number of Participants With Dose Reduction

Dose reduction and delays were done due to toxicity, or in the interest of participant's safety per investigator discretion. Requirement for more than 2 dose reductions resulted in permanent discontinuation of chemotherapy. Participants with dose reduction has been reported. (NCT01868022)
Timeframe: Median of 28.5 weeks

InterventionParticipants (Count of Participants)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A1
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A3
5 mg/kg GSK3052230 + Docetaxel: Arm B1
10 mg/kg GSK3052230 + Docetaxel: Arm B0
20 mg/kg GSK3052230 + Docetaxel: Arm B2
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C2
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0

[back to top]

Change From Baseline in Heart Rate

Heart rate was measured in a semi-supine position after 5 minutes of rest. Heart rate was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented. (NCT01868022)
Timeframe: Baseline and up to Median of 28.5 weeks

InterventionBeats per minute (bpm) (Mean)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A-0.3
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A3.2
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A8.0
5 mg/kg GSK3052230 + Docetaxel: Arm B28.0
10 mg/kg GSK3052230 + Docetaxel: Arm B10.5
20 mg/kg GSK3052230 + Docetaxel: Arm B0.6
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C-5.0
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C2.8
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C24.4

[back to top]

Change From Baseline in Temperature

Temperature was measured in a semi-supine position after 5 minutes of rest. Temperature was measured before start of first chemotherapy infusion and within 20 minutes before start of GSK3052230 infusion on Day 1 of every cycle and Baseline. Baseline is defined as the most recent, non-missing value prior to or on the first study GSK3052230 treatment dose date. Change from Baseline is calculated as visit value minus Baseline value. The worst-case post-Baseline values has been presented. (NCT01868022)
Timeframe: Baseline and up to Median of 28.5 weeks

InterventionDegree Celsius (Mean)
5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A-0.30
10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A-0.38
20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A0.35
5 mg/kg GSK3052230 + Docetaxel: Arm B0.10
10 mg/kg GSK3052230 + Docetaxel: Arm B1.03
20 mg/kg GSK3052230 + Docetaxel: Arm B-0.03
10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C-0.23
15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C-0.16
20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C0.12

[back to top]

Kaplan-Meier Estimates of Overall Survival

Overall survival was defined as the time from the date of randomization to the date of death (from any cause). (NCT01881230)
Timeframe: From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Interventionmonths (Median)
Arm A: Nab-Paclitaxel + Gemcitabine12.1
Arm B: Nab-Paclitaxel + Carboplatin16.8
Arm C: Gemcitabine + Carboplatin12.6

[back to top]

Kaplan-Meier Estimates of Progression-Free Survival (PFS) Based on Investigator Assessment.

PFS was defined as the time from the date of randomization to the date of disease progression or death from any cause on or prior to the data cutoff date for the statistical analysis, whichever occurred earlier. Tumor responses were assessed every 6 weeks using, Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and defined as: Complete response (CR) is the disappearance of all target lesions; Partial response (PR) occurs when at least a 30% decrease in the sum of diameters of target lesions from baseline; Stable disease is neither sufficient shrinkage to qualify for a PR nor sufficient increase of lesions to qualify for Progressive disease (PD); Progressive Disease- is at least a 20% increase in the sum of diameters of target lesions from nadir. (NCT01881230)
Timeframe: From date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Interventionmonths (Median)
Arm A: Nab-Paclitaxel + Gemcitabine5.5
Arm B: Nab-Paclitaxel + Carboplatin8.3
Arm C: Gemcitabine + Carboplatin6.0

[back to top]

Percentage of Participants Who Discontinued From All Study Treatment Due to TEAEs

Treatment-emergent adverse events (TEAEs) were defined as any AEs that begin or worsen with an onset date on or after the date of the first dose of IP through 28 days after the last dose. (NCT01881230)
Timeframe: From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

Interventionpercentage of participants (Number)
Arm A: Nab-Paclitaxel + Gemcitabine21.7
Arm B: Nab-Paclitaxel + Carboplatin26.6
Arm C: Gemcitabine + Carboplatin21.9

[back to top]

Percentage of Participants With an Objective Complete or Partial Overall Response by Investigator Assessment.

Percentage of participants with an Objective Complete or Partial Overall Response according to RECIST 1.1 and defined as: Complete response-disappearance of all target lesions; partial response at least a 30% decrease in the sum of diameters of target lesions from baseline; stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for Progressive disease (PD)• Progressive Disease- At least a 20% increase in the sum of diameters of target lesions from nadir. (NCT01881230)
Timeframe: Disease response was assessed every 6 weeks; from date of randomization to data cut-off date of 16 December 2016; total length of time on study was 31 months for Arm A, 34 months for Arm B and 35 months for Arm C

Interventionpercentage of participants (Number)
Arm A: Nab-Paclitaxel + Gemcitabine39.3
Arm B: Nab-Paclitaxel + Carboplatin73.4
Arm C: Gemcitabine + Carboplatin43.9

[back to top]

Number of Participants With Treatment Emergent Adverse Events (TEAEs)

Treatment-emergent adverse events (TEAEs) were defined as any AEs that began or worsened with the onset date on or after the date of the first dose of IP through 28 days after the last dose. A serious AE (SAE) = any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. The severity of AEs was graded based on the participant's symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.0); AEs were evaluated for severity as follows: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death. (NCT01881230)
Timeframe: From randomization through to 28 days after the last dose of IP; up to data cut off date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

,,
Interventionparticipants (Number)
Any TEAEAny Grade 3 or Higher TEAETreatment-related TEAETreatment-related, Grade 3 or Higher TEAESerious TEAETreatment-related Serious TEAETEAE Leading to Discontinuation (D/C) of IPTreatment Related (TR) TEAE Leading to D/C of IPTEAE Leading to Dose Reduction (DR) of IPTreatment related TEAE Leading to DR of IPTEAE Leading to Dose Interruption (DI) of IPTR TEAE Leading to DI of IPTEAE leading to D/C of nab-PaclitaxelTR TEAE leading to D/C of nab-PaclitaxelTEAE leading to DR of nab-PaclitaxelTR TEAE leading to DR of nab-PaclitaxelTEAE leading to DI of nab-PaclitaxelTR TEAE leading to DI of nab-PaclitaxelTEAE leading to D/C of GemcitabineTR TEAE leading to D/C of GemcitabineTEAE leading to DR of GemcitabineTR TEAE leading to DR of GemcitabineTEAE leading to DI of GemcitabineTR TEAE leading to DI of GemcitabineTEAE leading to D/C of CarboplatinTR TEAE leading to D/C of CarboplatinTEAE leading to DR of CarboplatinTR TEAE leading to DR of CarboplatinTEAE leading to DI of CarboplatinTR TEAE leading to DI of CarboplatinTEAE Leading to DeathTreatment Related TEAE leading to death
Arm A: Nab-Paclitaxel + Gemcitabine6046593522101612232331271611222131271371818312400000021
Arm B: Nab-Paclitaxel + Carboplatin6351624320929272020504417131919504400000028251717504410
Arm C: Gemcitabine + Carboplatin6454604625131512252350440000001392523494315122120504321

[back to top]

Percentage of Participants Experiencing Dose Modifications (Reductions and Interruptions)

The number of participants with dose modifications occurring during the treatment period. Dose reductions and interruptions are typically caused by clinically significant laboratory abnormalities and /or treatment emergent adverse events/toxicities. (NCT01881230)
Timeframe: From randomization through to 28 days after the last dose of IP; up to data-cut off of date of 16 Dec 2016; maximum treatment duration of study drug exposure was 108.3 weeks for Arm A, 83 weeks for Arm B, 110.1 weeks for Arm C

,,
Interventionpercentage of participants (Number)
≥ one DR for both IPs≥ one DI for both IPs≥ one dose missed for both IPs
Arm A: Nab-Paclitaxel + Gemcitabine33.338.348.3
Arm B: Nab-Paclitaxel + Carboplatin46.970.345.3
Arm C: Gemcitabine + Carboplatin51.673.456.3

[back to top]

Percentage of Participants Who Initiated Cycle 6 Receiving Doublet Combination Therapy

The percentage of participants who initiated Cycle 6 receiving doublet combination therapy regardless of the need for dose modifications. (NCT01881230)
Timeframe: Cycle 6

Interventionpercentage of participants (Number)
Arm A: Nab-Paclitaxel + Gemcitabine55.7
Arm B: Nab-Paclitaxel + Carboplatin64.1
Arm C: Gemcitabine + Carboplatin50.0

[back to top]

Proportion of Patients With Grade III or IV Oropharyngeal Bleeding or Positive Margins

"Surgery quality was evaluated based on grade 3-4 bleeding events per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 during surgery and positive margins after surgery. Per CTCAE v5.0, grade 3 = severe and grade 4 = life-threatening.~Having grade 3-4 bleeding or positive margins indicates worse outcomes." (NCT01898494)
Timeframe: Assessed during surgery and directly after surgery

Interventionproportion of participants (Number)
Arm S (Surgery)0.091

[back to top]

Progression-free Survival Rate at 2 Years

Progression-free survival is defined as the time from randomization/assignment of post-surgical treatment to the appearance of lesions, including primary, nodal or new site, or death, whichever occurs first. These patients are considered disease-free after surgery so the appearance of any lesions is counted as progression. Kaplan-Meier estimate was used to characterize progression-free survival rate at 2 years. (NCT01898494)
Timeframe: Assessed every 3 months for 2 years

Interventionproportion of participants (Number)
Arm S (Surgery) Then Arm A (Low Risk, Observation)0.969
Arm S (Surgery) Then Arm B (Intermediate Risk, Low-dose IMRT)0.949
Arm S (Surgery) Then Arm C (Intermediate Risk, Standard-dose IMRT)0.96
Arm S (Surgery) Then Arm D (High Risk, IMRT, Chemotherapy)0.907

[back to top]

Swallowing Function Before Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)

"The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life (my swallowing impacts my day-to-day life). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning)." (NCT01898494)
Timeframe: Assessed at baseline

Interventionscore on a scale (Mean)
Arm S (Surgery) Then Arm A (Low Risk, Observation)89.1
Arm S (Surgery) Then Arm B (Intermediate Risk, Low-dose IMRT)90.2
Arm S (Surgery) Then Arm C (Intermediate Risk, Standard-dose IMRT)87.4
Arm S (Surgery) Then Arm D (High Risk, IMRT, Chemotherapy)88.2

[back to top]

Swallowing Function After Surgery Assessed Using MD Anderson Dysphagia Inventory (MDADI)

"The MDADI measures swallowing-related quality of life (QOL) in patients with swallowing dysfunction in a 20-item written questionnaire. It evaluates the patient's physical (P), emotional (E) and functional (F) perceptions of swallowing dysfunction. This instrument has been psychometrically validated in head and neck cancer patients. Two summary scores can be obtained from the MDADI: 1) global and 2) composite. The global scale is a single question, scored individually, to assess the overall impact that swallowing abilities have on quality of life (my swallowing impacts my day-to-day life). The composite MDADI score summarizes overall performance on remaining 19-items of the MDADI, as a weighted average of the physical, emotional, and functional subscale questions. This study reports the composite MDADI score. The summary MDADI scores are normalized to range from 20 (extremely low functioning) to 100 (high functioning)." (NCT01898494)
Timeframe: Assessed 4-6 weeks after surgery

Interventionscore on a scale (Mean)
Arm S (Surgery) Then Arm A (Low Risk, Observation)75.5
Arm S (Surgery) Then Arm B (Intermediate Risk, Low-dose IMRT)76.3
Arm S (Surgery) Then Arm C (Intermediate Risk, Standard-dose IMRT)69.6
Arm S (Surgery) Then Arm D (High Risk, IMRT, Chemotherapy)73.3

[back to top]

Quality of Life (QOL) at 6 Months After Treatment Assessed by Functional Assessment of Cancer Therapy - Head and Neck Cancer (FACT-HN) Total Score

The FACT-H&N (version 4) consists of a cancer-specific questionnaire, FACT-G, in addition to 12 H&N cancer-specific items (the HN subscale). FACT-G is a 27-item measure that assesses general cancer quality of life. FACT-HN total score ranges between 0 and 148. The higher the score, the better the QOL. (NCT01898494)
Timeframe: Assessed at 6 months after treatment

Interventionscore on a scale (Mean)
Arm S (Surgery) Then Arm A (Low Risk, Observation)128.5
Arm S (Surgery) Then Arm B (Intermediate Risk, Low-dose IMRT)121.02
Arm S (Surgery) Then Arm C (Intermediate Risk, Standard-dose IMRT)117.8
Arm S (Surgery) Then Arm D (High Risk, IMRT, Chemotherapy)114.6

[back to top]

Pathologic Complete Response Rate (

The absence of carcinoma (pT0 disease) and the absence of microscopic lymph node metastases (N0) on the final cystectomy specimen. (NCT01916109)
Timeframe: 1 year

Interventionparticipants (Number)
Gemcitabine, Carboplatin, and Panitumumab (GCaP)3

[back to top]

Number of Patients With a Pathological Complete Response (pCR) Who Received Targeted Therapy With Trastuzumab and Pertuzumab or Bevacizumab Predicted by Genomically-derived Molecular Subtypes.

Number of patients with a pathological complete response (pCR) who received targeted therapy with trastuzumab and pertuzumab or bevacizumab predicted by genomically-derived molecular subtypes (HER2 positive or HER2 negative. pCR is defined as absence of invasive cancer in breast or lymph nodes after neoadjuvant chemotherapy. (NCT01959490)
Timeframe: Up to 30 days after last cycle of treatment

InterventionParticipants (Count of Participants)
Cohort 1P (HER2 Positive)4
Cohort 1T (HER2 Positive)6
Cohort II (HER2 Negative)3

[back to top]

Overall Survival

The estimated distributions of overall survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses. (NCT01959698)
Timeframe: From the start of treatment until death for any reason, assessed up to 5 years

Interventionmonths (Median)
Treatment (Carfilzomib, Rituximab, Chemotherapy)22.6

[back to top]

MTD Defined as the Dose of Carfilzomib Added to Standard R-ICE Chemotherapy Which, if Exceeded, Would Put the Patient at an Undesirable Risk of Medically Unacceptable Dose-limiting Toxicities (Phase I)

(NCT01959698)
Timeframe: 28 days

Interventionmg/m2 (Number)
Dose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)NA
Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)NA
Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)NA
Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)NA
Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)NA
Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)NA
Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)NA

[back to top]

Overall Response Rate (PR + CR)

Overall response rate (CR and PR) after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a single nodule) No clinically enlarged liver or spleen) (NCT01959698)
Timeframe: The time measurement criteria are first met for CR until the first date that recurrent disease is objectively documented, assessed up to 12 weeks

Interventionpercentage of participants (Number)
Treatment (Carfilzomib, Rituximab, Chemotherapy)66

[back to top]

Complete Response Rate According to the International Working Group Response Criteria as Reported by the Revised Cheson Criteria

Efficacy rates were estimated using simple relative frequencies. Complete response rate after 3 cycles of C R ICE in patients age of 18 to 75 with relapsed/refractory CD20-positive DLBCL treated with rituximab-based immunochemotherapy (e.g., R-CHOP, R-EPOCH, R-HyperCVAD, etc.) induction. Response was based on a Modified Cheson Criteria with Complete response (CR): All lesions with a longest diameter ≤ 15 mm or short axis ≤ 10 mm (Not palpable during the clinical examination, No visible nodule on imaging, And disappearance of all non-nodal target lesions Or in case of hypermetabolic disease on the baseline PET scan, negative PET scan whatever the appearance of lesions on CT) and Partial Response (PR): ≥ 50 % of sum of the products of the diameters (SPD) of target lesions or in the case of hypermetabolic lesions on the baseline PET scan, persistence of at least one PET-positive site without progression of other lesions on CT (≥ 50 % of SPD of target lesions (or longest diameter if a si (NCT01959698)
Timeframe: Up to 5 years

Interventionpercentage of participants (Number)
Treatment (Carfilzomib, Rituximab, Chemotherapy)48

[back to top]

Progression-free Survival

The estimated distributions of progression-free survival will be obtained using the Kaplan-Meier method. Corresponding confidence intervals using the methodology of Brookmeyer and Crowley will be computed. It is assumed a priori that any drop out times will be non-informative in terms of the censoring mechanism. Groups defined by levels of categorical or dichotomized numeric demographic/baseline variables will be compared in regards to time-to-event distributions using the log-rank test. Cox proportional hazards model regression will be utilized for multivariate analyses. (NCT01959698)
Timeframe: Up to 5 years

Interventionmonths (Median)
Treatment (Carfilzomib, Rituximab, Chemotherapy)15.2

[back to top]

Toxicity of the Addition of Carfilzomib to R-ICE at the MTD, Assessed by the CTEP Version 4.0 of the NCI CTCAE

Count of participants that experienced serious adverse events assessed by the CTEP version 4.0 of the NCI CTCAE (NCT01959698)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Dose Level 1: Carfilzomib 10mg/m2(d1-2; d8-9)2
Dose Level 2: Carfilzomib 15mg/m2(d1-2; d8-9)0
Dose Level 3: Carfilzomib 20mg/m2(d1-2; d8-9)0
Dose Level 4: Carfilzomib 20mg/m2(d1-2); 27mg/m2(d8-9)1
Dose Level 5: Carfilzomib 20mg/m2(d1-2); 36mg/m2(d8-9)1
Dose Level 6: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)3
Expansion Cohort: Carfilzomib 20mg/m2(d1-2); 45mg/m2(d8-9)4

[back to top]

Duration of Response

"Duration of response (DOR) was calculated as the time from the first objective response (PR or CR) to disease progression per RECIST v1.1 based on the central, independent, blinded radiologists' review.~DOR was only calculated for participants with an objective response. For responders not meeting the criterion for progression by the end of the study, DOR was censored at the date of the last evaluable tumor assessment.~Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions." (NCT01966003)
Timeframe: Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Interventionmonths (Median)
ABP 2155.8
Bevacizumab5.6

[back to top]

Percentage of Participants With an Objective Response

"Tumor assessments were performed by central, independent, blinded radiologists according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 using computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest and abdomen. Objective response is defined as a best overall response of partial response (PR) or complete response (CR) as defined by RECIST v1.1. All participants who did not meet the criteria for CR or PR by the end of the study were considered non-responders.~CR: Disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes must be reduced in short axis to < 10 mm.~PR: Disappearance of all target lesions with persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, and no new lesions, or, at least a 30% decrease in the sum of diameters of target lesions, with no progression of existing non-target lesions and no new lesions." (NCT01966003)
Timeframe: Disease assessments were performed at weeks 1, 7, 13, 19, and approximately every 9 weeks thereafter. The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Interventionpercentage of participants (Number)
ABP 21539.0
Bevacizumab41.7

[back to top]

Progression-free Survival

"Progression-free survival (PFS) was defined as the time from the randomization date to the date of disease progression using RECIST v1.1 based on the central, independent, blinded radiologists' review, or death. Participants who were alive and did not meet the criteria for progression by the end of the study were censored at their last evaluable disease assessment date. Participants with no evaluable tumor assessments after randomization who did not die by the end of the study were censored on the randomization date.~Progressive Disease was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm, or, unequivocal progression of existing non-target lesions, or any new lesions." (NCT01966003)
Timeframe: From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Interventionmonths (Median)
ABP 2156.6
Bevacizumab7.9

[back to top]

Number of Participants Who Developed Anti-drug Antibodies

Two validated assays were used to detect the presence of anti-ABP 215 antibodies. Samples were first tested in an electrochemiluminescence (ECL)- based bridging immunoassay to detect antibodies capable of binding to ABP 215 (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a non-cell based target binding assay to determine neutralizing activity against ABP 215 (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. (NCT01966003)
Timeframe: 44 weeks (6 months after end of treatment)

,
Interventionparticipants (Number)
Binding antibody positiveNeutralizing antibody positive
ABP 21540
Bevacizumab70

[back to top]

Number of Participants With Adverse Events

"Adverse events (AEs) were graded for severity according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4, and according to the following scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death due to AE.~A serious adverse event (SAE) is defined as an AE that meets at least 1 of the following serious criteria:~fatal~life-threatening~required inpatient hospitalization or prolongation of existing hospitalization~resulted in persistent or significant disability/incapacity~congenital anomaly/birth defect~other medically important serious event" (NCT01966003)
Timeframe: up to 19 weeks

,
Interventionparticipants (Number)
Any adverse eventAny grade ≥ 3 adverse eventAny fatal adverse eventAny serious adverse eventAny AE leading to discontinuation of study drugAny AE leading to discontinuation of chemotherapyAny AE leading to dose delay of study drugAny AE leading to dose delay of any chemotherapyAny AE leading to dose reduction of chemotherapy
ABP 21530813913856174738648
Bevacizumab28913711715359698349

[back to top]

Overall Survival

"Overall survival (OS) was defined as the time from the randomization date to date of death. Participants alive at the end of study were censored at the last date known to be alive, derived from dates collected within the study that implied a participant was alive.~Participants were followed for survival status during the treatment phase and thereafter every 9 weeks until the end of the clinical study, consent was withdrawn, they were lost to follow-up, died, or had proscribed therapy (eg, commercial bevacizumab, non-study anti-cancer treatment)." (NCT01966003)
Timeframe: From randomization until the end of study; The mean actual follow-up time from randomization was 4.7 and 5.0 months for ABP 215 and bevacizumab, respectively.

Interventionmonths (Median)
ABP 215NA
BevacizumabNA

[back to top]

Phase 1b: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Sampling Time AUC (0-t) of Tepotinib, Its Metabolites and Gefitinib

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration is at or above the lower limit of quantification (LLLQ). AUC(0-t) was calculated according to the mixed log-linear trapezoidal rule. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
Interventionnanogram*hour per milliliter (ng*h/mL) (Geometric Mean)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A Day15 of Cycle 1MSC2571107A Day 1 of Cycle 1MSC2571107A Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg62801560016804420248872NA7690
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg92102220017707530324188029307080

[back to top]

Phase 1b: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC 0-infinity) of Tepotinib, Its Metabolites and Gefitinib

The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
Interventionng*h/mL (Geometric Mean)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of Cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mgNANANANANANANANA
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mgNANANANANANANANA

[back to top]

Phase 1b: Area Under the Plasma Concentration-Time Curve Within 1 Dosing Interval (AUC 0-tau) of Tepotinib, Its Metabolites and Gefitinib

AUC (0-tau) is the area under the plasma concentration time curve within 1 dosing interval. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
Interventionng*h/mL (Geometric Mean)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of Cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg62801560016804420248872NA7690
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg92102220017707530324188029307080

[back to top]

Phase 1b: Average Observed Plasma Concentration (Cavg) of Tepotinib, Its Metabolites and Gefitinib

Cavg is the average plasma concentration within 1 dosing interval obtained directly from the concentration versus time curve. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

,
Interventionng/mL (Geometric Mean)
TepotinibMSC2571109AMSC2571107AGefitinib
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg65418536.4321
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg92431478.3295

[back to top]

Phase 1b: Maximum Observed Plasma Concentration (Cmax) of Tepotinib, Its Metabolites and Gefitinib

Cmax is the maximum observed plasma concentration obtained directly from the concentration versus time curve. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
InterventionNanogram per Milliliter (ng/mL) (Geometric Mean)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of Cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg37576313228016.844.9NA432
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg575105014944424.394.9215366

[back to top]

Phase 1b: Minimum Observed Plasma Concentration (Cmin) of Tepotinib, Its Metabolites and Gefitinib

Cmin is minimum observed plasma concentration obtained directly from the concentration versus time curve. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

,
Interventionng/mL (Geometric Mean)
TepotinibMSC2571109AMSC2571107AGeftinib
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg53415632.8231
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg73527068.7190

[back to top]

Phase 1b: Number of Participants With Death and Reasons

Number of participants with death due to progressive disease (PD), adverse event (AE) related to study treatment, AE not related to study treatment were reported. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Number of participants with deaths due to PD, AE related to study treatment, AE not related to study treatment were reported. (NCT01982955)
Timeframe: Up to 175 weeks

,
InterventionParticipants (Count of Participants)
Death due to PDDeath due to AE related to study treatmentDeath due to AE not related to study treatment
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg001
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg300

[back to top] [back to top] [back to top]

Phase 1b: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)

The laboratory measurements included hematology and coagulation, biochemistry and urinalysis. (NCT01982955)
Timeframe: Up to 175 weeks

,
InterventionParticipants (Count of Participants)
Amylase increasedLipase increasedNeutrophil count decreasedHyperglycemiaHypocalcemiaHyponatremiaHypoproteinemia
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg2100101
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg2212020

[back to top]

Phase 2: Number of Participants With Clinically Significant Abnormalities in Vital Signs

Vital signs assessment included blood pressure, heart rate, respiratory rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionParticipants (Count of Participants)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)0
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)0
Phase 2: Single-arm Cohort (MET+ T790M Positive)0

[back to top]

Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported. (NCT01982955)
Timeframe: Up to 175 weeks

,
InterventionParticipants (Count of Participants)
Any TEAEsAny Serious TEAEs
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg64
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg127

[back to top]

Phase 2: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2

ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionParticipants (Count of Participants)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)6
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)1
Phase 2: Single-arm Cohort (MET+ T790M Positive)1

[back to top] [back to top]

Phase 1b: Time to Reach Maximum Plasma Concentration (Tmax) of Tepotinib, Its Metabolites and Gefitinib

Tmax is time to reach maximum observed plasma concentration obtained directly from the concentration versus time curve. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
InterventionHours (Median)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of Cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg8.006.0024.000.0024.000.13NA4.00
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg9.019.0024.000.0024.000.258.008.00

[back to top]

Phase 2: Number of Participants With Death and Reasons

An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. Number of participants with deaths due to progression disease (PD), AE related to study treatment, unknown reason was reported. (NCT01982955)
Timeframe: Up to 328 weeks

,,
InterventionParticipants (Count of Participants)
Death due to disease progressionDeath due to AE related to study treatmentDeath due to unknown reason
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)1505
Phase 2: Single-arm Cohort (MET+ T790M Positive)802
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)2102

[back to top] [back to top]

Phase 2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings

ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionParticipants (Count of Participants)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)2
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)1
Phase 2: Single-arm Cohort (MET+ T790M Positive)0

[back to top]

Phase 1b: Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). CR: defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionPercentage of Participants (Number)
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg33.3
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg33.3

[back to top]

Phase 2 (Non-Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). CR: defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionPercentage of Participants (Number)
Phase 2: Single-arm Cohort (MET+ T790M Positive)0

[back to top]

Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)

Progression-free survival (assessed by Independent Review Committee) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the IRC or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionMonths (Median)
Phase 2: Single-arm Cohort (MET+ T790M Positive)2.63

[back to top]

Phase 2 (Non-Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Investigator

Progression-free survival (assessed by Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease by the Investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionMonths (Median)
Phase 2: Single-arm Cohort (MET+ T790M Positive)1.41

[back to top]

Phase 2 (Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR:disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD:an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR/PD at minimum interval of 42 days after randomization/start of study treatment. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionPercentage of Participants (Number)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)83.9
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)70.8

[back to top]

Phase 2 (Randomized Part Only): Percentage of Participants With Objective Response Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

Objective response (OR) was defined as the percentage of participants who had achieved complete response (CR) or partial response (PR) as the best overall response according to local radiological assessments from randomization/the first administration of the study treatment to the first observation of disease progression (PD). CR: defined as disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR: defined as at least a 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD defined as an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionPercentage of Participants (Number)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)45.2
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)33.3

[back to top]

Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by Independent Review Committee (IRC)

Progression-free survival (assessed by Independent Review Committee) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease (PD) by the IRC or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 mm. PFS was measured using Kaplan-Meier (KM) estimates. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionMonths (Median)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)10.15
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)4.34

[back to top]

Phase 2 (Randomized Part Only): Progression-free Survival (PFS) Based on Tumor Assessment by the Investigator

Progression-free survival (assessed by the Investigator) time was defined as the time in months from randomization to either first observation of radiologically confirmed progression disease (PD) by the investigator or occurrence of death due to any cause within 84 days of either randomization or the last tumor assessment. PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter (mm). PFS was measured using Kaplan-Meier (KM) estimates. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionMonths (Median)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)4.86
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)4.37

[back to top]

Phase 2: (Non-Randomized Part Only): Overall Survival (OS) Time

Overall survival time was measured as time in months between the date of randomization and the date of death. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionMonths (Median)
Phase 2: Single-arm Cohort (MET+ T790M Positive)25.86

[back to top]

Phase 2: (Randomized Part Only): Overall Survival (OS) Time

Overall survival time was measured as time in months between the date of randomization and the date of death. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionMonths (Median)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)17.25
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)19.48

[back to top]

Phase 2: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status Scale Score at End of Treatment (EOT)

EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnoea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL. (NCT01982955)
Timeframe: Baseline and EOT (up to 110 weeks)

InterventionUnits on a Scale (Mean)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)-16.29
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)-2.78
Phase 2: Single-arm Cohort (MET+ T790M Positive)-24.19

[back to top]

Phase 1b: Apparent Volume of Distribution (Vz/F) During the Terminal Phase of Tepotinib, Its Metabolites and Gefitinib

The Vz/f was defined as the theoretical volume in which the total amount of required to uniformly distribute to produce the desired plasma concentration. Apparent volume of distribution after oral dose (Vz/F) was influenced by the fraction absorbed. The Vz/f was calculated by dividing the dose with area under the concentration time curve from time zero to infinity multiplied with terminal elimination rate constant Lambda(z). Vz/f=Dose/AUC(0-inf) multiply Lambda(z). (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
InterventionLiter (Geometric Mean)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of Cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mgNANANANANANANANA
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mgNANANANANANANANA

[back to top]

Phase 1b: Apparent Total Body Clearance From Plasma (CL/F) of Tepotinib and Gefitinib

The CL/f is a measure of the rate at which it was metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed. The CL/F from plasma was calculated using the formula: Dose divided by area under the concentration time curve from time zero to infinity (AUC0-inf). (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 15 of Cycle 1 (each Cycle is 21 days)

,
Interventionliter per hour (L/h) (Geometric Mean)
TepotinibGefitinib
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg17.332.5
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg20.335.3

[back to top]

Phase 1b: Apparent Terminal Half-Life (t1/2) of Tepotinib, Its Metabolites and Gefitinib

Apparent terminal half-life was defined as the time required for the plasma concentration of drug to decrease 50 percent in the final stage of its elimination. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
InterventionHours (Median)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of Cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mgNANANANANANANANA
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mgNANANANANANANANA

[back to top]

Phase 1b: Apparent Terminal Elimination Rate Constant Lambda(z) of Tepotinib, Its Metabolites and Gefitinib

Lambda(z) was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
Intervention1 per hour (Geometric Mean)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of Cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mgNANANANANANANANA
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mgNANANANANANANANA

[back to top]

Phase 2: Time-to-Symptom Progression (TTSP)

TTSP was measured from randomization to symptomatic progression by lung cancer symptom scale (LCSS) used to measure symptom changes relevant to quality of life (QoL).It consisted of 9 items focused on cancer symptoms (loss of appetite, fatigue, cough, shortness of breath, blood in sputum, pain, symptoms of cancer, illness affecting normal activity, QoL).For each symptom score distance from left boundary to point where participant has marked line was measured in millimeters (mm).Total scale length was 100 mm. Symptomatic progression was defined as increase/worsening of average symptomatic burden index (ASBI) (mean of 6 major lung cancer specific symptom scores);Worsening defined as 10% increase of scale breadth from baseline. Score 0 indicate no/minimum symptoms;100 indicates maximum level of symptoms. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionMonths (Median)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)5.75
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)7.95
Phase 2: Single-arm Cohort (MET+ T790M Positive)2.63

[back to top]

Phase 2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation

An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to permanent treatment discontinuation were reported. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionParticipants (Count of Participants)
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)3
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)1
Phase 2: Single-arm Cohort (MET+ T790M Positive)2

[back to top]

Phase 2: Number of Participants With Laboratory Test Abnormalities of Grade 3 or Higher Severity Based on NCI-CTCAE Version 4.03 Reported as Treatment-Emergent Adverse Events (TEAEs)

The laboratory measurements included hematology and coagulation, biochemistry and urinalysis. (NCT01982955)
Timeframe: Up to 328 weeks

,,
InterventionParticipants (Count of Participants)
AnaemiaNeutropeniaAlanine aminotransferase increasedAmylase increasedGamma-glutamyltransferase increasedLipase increasedNeutrophil count decreasedWhite blood cell count decreasedHyponatremiaHypokalemiahypophosphatemiaHypoalbuminemia
Phase 2: Pemetrexed and Cisplatin/Carboplatin (MET + T790 Negative)710212323210
Phase 2: Single-arm Cohort (MET+ T790M Positive)000201000000
Phase 2: Tepotinib 500 mg + Gefitinib 250 mg (MET + T790 Negative)001705211001

[back to top]

Phase 1b: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Leading to Permanent Treatment Discontinuation

An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Term TEAE is defined as AEs starting/worsening after first intake of the study drug. TEAEs included both Serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to permanent treatment discontinuation were reported. (NCT01982955)
Timeframe: Up to 175 weeks

,
InterventionParticipants (Count of Participants)
TEAE Leading Permanent Tepotinib DiscontinuationTEAE Leading Permanent Gefitinib Discontinuation
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg00
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg21

[back to top]

Phase 2 (Non-Randomized Part Only): Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR:disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD:an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR/PD at minimum interval of 42 days after randomization/start of study treatment. (NCT01982955)
Timeframe: Up to 328 weeks

InterventionPercentage of Participants (Number)
Phase 2: Single-arm Cohort (MET+ T790M Positive)40

[back to top]

Phase 1b: Number of Participants Experiencing at Least One Dose Limiting Toxicity (DLT)

Dose limiting toxicity (DLT) using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 was defined as toxicities at any dose level and judged to be related to the study treatment by investigator and/or the sponsor. DLTs included Grade 4 neutropenia for more than 7 days; Grade greater than or equal to (>=) 3 febrile neutropenia for more than 1 day; Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with non-traumatic bleeding; Grade >= 3 uncontrolled nausea/vomiting and/or diarrhea despite adequate and optimal treatment and Grade >= 3 any non-hematological adverse event (AE), except the aforementioned gastrointestinal events and alopecia. Number of participants who experienced DLT during Phase 1b were reported. (NCT01982955)
Timeframe: Day 1 to Day 21 of Cycle 1 (each cycle is 21 days)

InterventionParticipants (Count of Participants)
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg0
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg0

[back to top]

Phase 1b: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiograms (ECG) Findings

ECG parameters included heart rhythm, pulse rate intervals, QRS, QT intervals, RR intervals and corrected QT(QTc) intervals. Clinical significance was determined by the investigator. Number of participants with clinically significant abnormalities in 12-lead ECG were reported. (NCT01982955)
Timeframe: Up to 175 weeks

InterventionParticipants (Count of Participants)
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg0
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg0

[back to top]

Phase 1b: Number of Participants With Clinically Significant Abnormalities in Vital Signs

Vital signs assessment included blood pressure, heart rate, respiratory rate and body temperature. Number of Participants with any clinically significant abnormalities in vital signs were reported. Clinical significance was determined by the investigator. (NCT01982955)
Timeframe: Up to 175 weeks

InterventionParticipants (Count of Participants)
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg0
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg0

[back to top]

Phase 1b: Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Score of 2 or Higher Than 2

ECOG PS score is widely used by doctors and researchers to assess how a participants' disease is progressing, and is used to assess how the disease affects the daily living abilities of the participant, and determine appropriate treatment and prognosis. The score ranges from Grade 0 to Grade 5, where Grade 0 = Fully active, able to carry on all pre-disease performance without restriction, Grade 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (like light house work, office work), Grade 2 = Ambulatory and capable of all self-care but unable to carry out any work activities, Grade 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours and Grade 4 = Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair, Grade 5 = Death. Number of participants with ECOG performance status score of 2 or higher than 2 were reported. (NCT01982955)
Timeframe: Up to 175 weeks

InterventionParticipants (Count of Participants)
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg1
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg9

[back to top]

Phase 1b: Percentage of Participants With Disease Control Based on Tumor Response Assessment According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) Criteria

Disease control defined as CR, PR, or stable disease(SD) as the best overall response according to local radiological assessments from the date of randomization/the first administration of the study treatment to the first observation of PD. CR:disappearance of all target and non-target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR:at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum diameters. PD:an increase of at least 20% in the sum of the diameters of target lesions, taking as reference the smallest sum of the diameters of target lesions recorded since treatment started and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5mm. SD:as any cases that do not qualify for either PR or PD at minimum interval of 42 days after randomization/start of study treatment (NCT01982955)
Timeframe: Up to 328 weeks

InterventionPercentage of Participants (Number)
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mg50.0
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mg58.3

[back to top]

Phase 1b: Apparent Volume of Distribution During the Steady State (Vss/F) of Tepotinib, Its Metabolites and Gefitinib

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss/f after oral dose was influenced by the fraction absorbed. (NCT01982955)
Timeframe: Pre dose, 0.25, 0.5, 1, 2, 4, 8, 10 and 24 hours post dose on Day 1 and 15 of Cycle 1 (each Cycle is 21 days)

,
InterventionLiter (Geometric Mean)
Tepotinib: Day 1 of Cycle 1Tepotinib: Day 15 of Cycle 1MSC2571109A: Day 1 of Cycle 1MSC2571109A: Day 15 of cycle 1MSC2571107A: Day 1 of Cycle 1MSC2571107A: Day 15 of Cycle 1Gefitinib: Day 1 of Cycle 1Gefitinib: Day 15 of Cycle 1
Phase 1b: Tepotinib 300 mg + Gefitinib 250 mgNANANANANANANANA
Phase 1b: Tepotinib 500 mg + Gefitinib 250 mgNANANANANANANANA

[back to top]

Overall Response Rate

"The overall response rate (ORR) was defined as the percentage of participants for whom the best overall confirmed response was either complete response (CR) or partial response (PR) assessed by the investigator according to RECIST v1.1 criteria.~CR: Disappearance of all target and non-target lesions, no new lesions and normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters, or, the disappearance of all target lesions and persistence of one or more non-target lesion(s) and/or maintenance of tumor marker levels above normal limits." (NCT01987232)
Timeframe: From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

Interventionpercentage of participants (Number)
Carfilzomib 20/20 mg/m²60.0
Carfilzomib 20/27 mg/m²100.0
Carfilzomib 20/36 mg/m²66.7
Carfilzomib 20/45 mg/m²33.3
Carfilzomib 20/56 mg/m²33.3
All Participants46.9

[back to top]

Number of Participants With Dose-limiting Toxicities

"The maximum tolerated dose (MTD) was defined as the highest dose level at which < 33% of participants experienced a dose-limiting toxicity (DLT) during the first 21-day cycle. Dose-limiting toxicities were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. A DLT was defined as:~A grade 3 or greater non-hematologic toxicity that was assessed as related to carfilzomib by the investigator except in the case of neuropathy. A grade 2 or higher neuropathy with pain was considered a DLT.~Grade 4 neutropenia: absolute neutrophil count (ANC) < 500 mm³, lasting ≥ 7 days despite granulocyte colony stimulating factor support, or any febrile (temperature > 38.3°C) neutropenia (ANC < 1000 mm³).~Thrombocytopenia of any grade associated with clinically significant bleeding or platelet/blood transfusion~Grade 4 fatigue lasting ≥ 7 days~Grade 3 nausea, vomiting or diarrhea lasting ≥ 7 days." (NCT01987232)
Timeframe: First 21-day Cycle

InterventionParticipants (Count of Participants)
Carfilzomib 20/20 mg/m²0
Carfilzomib 20/27 mg/m²0
Carfilzomib 20/36 mg/m²0
Carfilzomib 20/45 mg/m²0
Carfilzomib 20/56 mg/m²1

[back to top]

Duration of Response

"Duration of response (DOR) was calculated for participants who achieved a confirmed CR or PR. defined as the time from first evidence of confirmed PR/CR to disease progression or death due to any cause. Median DOR was calculated using Kaplan-Meier methods. Participants with no baseline disease assessments, who started a new anticancer therapy before documentation of PD or death, with death or PD immediately after more than 1 consecutively missed disease assessment visit or alive without documentation of PD before the data cutoff date were censored.~DOR was originally specified as a secondary endpoint for the phase 2 portion of the study. Since phase 2 did not proceed, DOR was analyzed in phase 1b participants on an exploratory basis." (NCT01987232)
Timeframe: From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

Interventionmonths (Median)
Carfilzomib 20/20 mg/m²4.9
Carfilzomib 20/27 mg/m²5.0
Carfilzomib 20/36 mg/m²NA
Carfilzomib 20/45 mg/m²4.3
Carfilzomib 20/56 mg/m²4.5
All Participants4.8

[back to top]

Number of Participants With Adverse Events (AEs)

"The severity of each adverse event was assessed using the NCI-CTCAE Version 4.03 according to the following:~Grade 1 - Mild: Asymptomatic or mild symptoms; intervention not indicated~Grade 2 - Moderate: Minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL)~Grade 3 - Severe: Medically significant but not life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL~Grade 4 - Life-threatening~Grade 5 - Fatal.~A serious AE is an AE that met one or more of the following criteria:~Death~Life-threatening~Required inpatient hospitalization or prolongation of an existing hospitalization~Resulted in persistent or significant disability/incapacity~A congenital anomaly/birth defect~Important medical events that required medical or surgical intervention to prevent one of the outcomes above." (NCT01987232)
Timeframe: From first day of any study treatment (i.e., carfilzomib, carboplatin, or etoposide) up to 30 days after the last day of study treatment. The median overall duration of treatment was 16 weeks.

,,,,
InterventionParticipants (Count of Participants)
Any adverse eventAdverse events ≥ grade 3Serious adverse eventsAEs leading to disocontinuation of study drugFatal adverse events
Carfilzomib 20/20 mg/m²53110
Carfilzomib 20/27 mg/m²33100
Carfilzomib 20/36 mg/m²32100
Carfilzomib 20/45 mg/m²1513730
Carfilzomib 20/56 mg/m²54211

[back to top]

Progression-free Survival

"Progression-free survival (PFS) was specified as a primary endpoint for the phase 2 portion of the study. Since phase 2 did not proceed PFS was analyzed in phase 1b participants on an exploratory basis. PFS was defined as the time from the start of treatment to documented disease progression or death due to any cause, whichever occurred first. Disease progression was determined by the investigator according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, defined as at least a 20% increase in the size of target lesions (absolute increase ≥ 5 mm), unequivocal progression of existing non-target lesions, or any new lesions.~Median PFS was calculated using Kaplan-Meier methods. Participants with no baseline disease assessments, who started a new anticancer therapy before documentation of PD or death, with death or PD immediately after more than 1 consecutively missed disease assessment visit or alive without documentation of PD before the data cutoff date were censored. (NCT01987232)
Timeframe: From first dose of study drug until the end of treatment; median duration of treatment was 16 weeks.

Interventionmonths (Median)
Carfilzomib 20/20 mg/m²4.0
Carfilzomib 20/27 mg/m²6.4
Carfilzomib 20/36 mg/m²7.0
Carfilzomib 20/45 mg/m²2.9
Carfilzomib 20/56 mg/m²3.8
All Participants4.4

[back to top]

Overall Survival

Overall Survival (OS) was defined as the time from the date of randomization to the date of death, regardless of the cause of death. Participants who were alive at the time of the analysis were censored at the date of the last follow-up assessment. (NCT01998919)
Timeframe: Date of randomization until date of death or date of last follow-up assessment

Interventionweeks (Median)
Placebo Plus Chemotherapy75.7
Erlotinib Plus Chemotherapy74.1

[back to top]

Duration of Response

Duration of Response was defined similarly for complete responders and partial responders. CR was defined as the date CR was first recorded to the date on which PD was first noted or date of death. PR was defined as the date the first PR was recorded to the date of the first observation of PD or date of death. (NCT01998919)
Timeframe: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-study Phases

Interventionweeks (Median)
Placebo Plus Chemotherapy24.1
Erlotinib Plus Chemotherapy38.4

[back to top]

Percentage of Participants With Confirmed CR or PR as Assessed by RECIST

CR=disappearance of all target lesions; PR=at least a 30% decrease in sum of LD of target lesions, taking as reference the baseline sum LD. (NCT01998919)
Timeframe: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases

Interventionpercentage of participants (Number)
Placebo Plus Chemotherapy24.4
Erlotinib Plus Chemotherapy36.8

[back to top]

Percentage of Participants With Non-Progression at Week 16 as Assessed by RECIST

Non-progression defined as documented best overall tumor response of CR, PR, or SD (where SD was maintained for >16 weeks) per RECIST. (NCT01998919)
Timeframe: Week 16

Interventionpercentage of participants (Number)
Placebo Plus Chemotherapy53.8
Erlotinib Plus Chemotherapy64.5

[back to top]

Percentage of Participants With Non-Progression at Week 8 as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)

Non-progression defined as documented best overall tumor response of complete response (CR), partial response (PR), or stable disease (SD; where SD was maintained for greater than [>]8 weeks) per RECIST. Investigator's assessment of response used in all analyses. CR equals (=)disappearance of all target lesions; PR=at least a 30 percent (%) decrease in sum of longest diameter (LD) of target lesions, taking as reference the baseline sum LD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference smallest sum LD since treatment started. (NCT01998919)
Timeframe: Week 8

Interventionpercentage of participants (Number)
Placebo Plus Chemotherapy76.9
Erlotinib Plus Chemotherapy80.3

[back to top]

Progression-Free Survival (PFS)

PFS was defined as the interval between the day of randomization and the date of first documentation of progressive disease or date of death, whichever came first. (NCT01998919)
Timeframe: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases

Interventionweeks (Median)
Placebo Plus Chemotherapy23.4
Erlotinib Plus Chemotherapy30.4

[back to top]

Time to Progression

Time to progression was defined as the interval between the day of randomization and the first documentation of PD. Participants who were withdrawn from the study without documented progression and for whom there exists CRF evidence that evaluations have been made, were censored at 1) the date of the last tumor assessment, 2) last date in the drug log, or 3) last date of follow-up when the participant was known to be progression free, whichever was last. Participants without post-baseline tumor assessments but known to be alive were censored at the time of randomization. (NCT01998919)
Timeframe: Screening/Baseline, Day 22 of Cycles 2, 4 and 6 and every 8 weeks in Post-Study and Off-Study Phases

Interventionweeks (Median)
Placebo Plus Chemotherapy24.1
Erlotinib Plus Chemotherapy31.4

[back to top]

Percentage of Participants With Cardiac Toxicity Categorized According to National Cancer Institute CTCAE Version 4.0

Percentage of patients with grade 1 or higher toxicity from the Cardiac Disorders System Organ Class. (NCT02003209)
Timeframe: Up to 6 weeks post surgery

Interventionpercentage of pts with cardiac toxicity (Number)
Arm I (Combination Chemotherapy, Surgery, Radiation)4.46
Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation)4.46

[back to top]

Median Percentage of Tumor-infiltrating Lymphocytes (sTILS)

Percentage of Tumor-infiltrating lymphocytes present in the stroma in tissue specimen. (NCT02003209)
Timeframe: 2.8 years

,
Interventionpercentage of TILs (Median)
No pCRpCR
Arm I (Combination Chemotherapy, Surgery, Radiation)1010
Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation)1010

[back to top]

Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes by Menopausal Status

Proportion of patients with pCR evaluated histologically, and defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy calculated separately for premenopausal and postmenopausal women. (NCT02003209)
Timeframe: Up to 2.8 years (when all patients completed primary breast surgery)

,
Interventionpercentage of participants with pCR (Number)
Premenopausal WomenPostmenopausal Women
Arm I (Combination Chemotherapy, Surgery, Radiation)44.238.2
Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation)46.245.5

[back to top]

Percent of Patients With Pathologic Complete Response (pCR) in the Breast

Proportion of patients with pCR in the breast, defined as the absence of any invasive component in the resected breast specimen. (NCT02003209)
Timeframe: Up to 2.8 years (when all patients completed primary breast surgery)

Interventionpercentage of participants (Number)
Arm I (Combination Chemotherapy, Surgery, Radiation)44.4
Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation)47.1

[back to top]

Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes

Proportion of patients with pCR evaluated histologically, and defined as the absence of any invasive component in the resected breast specimen and all resected lymph nodes following completion of neoadjuvant therapy. (NCT02003209)
Timeframe: Up to 2.8 years (when all patients completed primary breast surgery)

Interventionpercentage of participants (Number)
Arm I (Combination Chemotherapy, Surgery, Radiation)41.2
Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation)45.8

[back to top]

Kaplan-Meier Probability of Being Alive at 1 Year

(NCT02004093)
Timeframe: 1 year

Interventionpercent (Number)
Chemotherapy + Pertuzumab88
Chemotherapy85

[back to top]

Kaplan-Meier Probability of Being Progression Free at 1 Year

(NCT02004093)
Timeframe: 1 year

Interventionpercent (Number)
Chemotherapy + Pertuzumab24
Chemotherapy19

[back to top]

Kaplan-Meier Probability of Maintaining a Response to at Least 1 Year

(NCT02004093)
Timeframe: 1 year

Interventionpercent (Number)
Chemotherapy + Pertuzumab18
Chemotherapy18

[back to top]

Kaplan-Meier Probability of No Disease or Progression at 1 Year

The probability of being event free (no disease progression or death events) at 1 year in participants remaining at risk. (NCT02004093)
Timeframe: 1 year

Interventionpercent (Number)
Chemotherapy + Pertuzumab24
Chemotherapy21

[back to top]

Overall Survival

Survival was the interval of time from date of first dose of study medication to date of death at any time. Participants who had not died were censored at the date of last contact when they were known to be alive. (NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment

Interventionmonths (Median)
Chemotherapy + Pertuzumab28.2
ChemotherapyNA

[back to top]

Percentage of Participants With a Best Overall Confirmed Response Based on Combined CA 125 and RECIST Measurements

"Response by tumor measurement occurred if there was documented and confirmed complete response (CR) or partial response (PR). For all participants, response was assessed by both the RECIST and by CA 125 levels, according to whether the participant had measurable or non-measurable disease at baseline. Response according to CA 125 levels was defined as at least a 50% reduction from baseline. The decrease had to be confirmed and maintained for at least 28 days. The confirmatory sample must have been less than or equal to the previous sample (within an assay variability of 10%). For overall response, the response categories were response, stable disease and progressive disease. Stable disease included 1) stable disease as defined by RECIST for solid tumors and 2) CA 125 levels that had not met the definition of response or progressive disease." (NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Interventionpercentage of participants (Number)
Chemotherapy + Pertuzumab74.3
Chemotherapy68.0

[back to top]

Percentage of Participants With Disease Progression or Death

Disease progression was assessed according to RECIST (Response Evaluation Criteria In Solid Tumors), for participants with measurable disease, or by changes in CA 125 (Cancer Antigen 125) according to GCIG (Gynecologic Cancer Inter Group) for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. (NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Interventionpercentage of participants (Number)
Chemotherapy + Pertuzumab87.8
Chemotherapy80.0

[back to top]

Progression-Free Survival

Progression-free survival was defined as the time from first administration of study drug (Study Day 1) to documented disease progression or death, whichever occurred earlier. Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress or died while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. (NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Interventionweeks (Median)
Chemotherapy + Pertuzumab34.1
Chemotherapy40.0

[back to top]

Time to Progressive Disease

The time to progressive disease is the interval of time from date of first dose of study medication to date of first documentation of progressive disease by either RECIST or CA 125 criteria. Participants who never progressed while being followed were censored at the last valid tumor measurement or CA 125 measurement. (NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression

Interventionweeks (Median)
Chemotherapy + Pertuzumab34.3
Chemotherapy37.3

[back to top]

Time To Response

Time to response was the date of first dose of study medication to the date of the first documentation of response, according to CA 125 criteria for all participants or response according to RECIST criteria for participants with measurable disease. If response was evaluable by both criteria, then the date of response was for the earlier of the two events. (NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment

Interventionweeks (Median)
Chemotherapy + Pertuzumab6.0
Chemotherapy6.3

[back to top]

Percentage of Participants Who Died

(NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until 2 years after last dose of treatment

Interventionpercentage of participants (Number)
Chemotherapy + Pertuzumab45.9
Chemotherapy41.3

[back to top]

Duration of Response

For participants who achieved a response, the duration of response was defined as the interval between initial documentation of response to the first documentation of disease progression or death. Participants who responded and did not progress or die while on study or while being followed were censored at the last valid tumor or CA 125 measurement. (NCT02004093)
Timeframe: Day 15 of Cycles 2, 4, 6, and Day 15 of all Cycles from Cycle 7 to 17 until disease progression up to 104 weeks

Interventionweeks (Median)
Chemotherapy + Pertuzumab28.7
Chemotherapy37.0

[back to top]

Percentage of Participants With Disease Progression

Disease progression was assessed according to RECIST, for participants with measurable disease, or by changes in CA 125 according to GCIG for all participants. Participants who did not progress while being followed were censored at the time of the last valid tumor assessment or valid CA 125 assessment. (NCT02004093)
Timeframe: Screening and Day 15 of Cycles 2, 4, 6, and Day 15 of all cycles from Cycle 7 to 17 until disease progression

Interventionpercentage of participants (Number)
Chemotherapy + Pertuzumab83.8
Chemotherapy76.0

[back to top]

Event-free Survival (EFS)

Event-free survival (EFS) is defined as the time from diagnosis to the earliest of disease progression/recurrence, second malignancy or death from any cause, or to the date of last follow-up for patients without events. EFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's. (NCT02017964)
Timeframe: 2 years from diagnosis

Interventionpercent probability (Number)
All Eligible Patients (Combination Chemotherapy)52.0

[back to top]

Overall Survival (OS)

Overall Survival (OS) is defined as the time from diagnosis to death from any cause, or to the date of last follow-up for survivors. OS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's, as the data are not mature to 72 months. (NCT02017964)
Timeframe: Assessed up to 72 months, reported at 2 years from diagnosis

Interventionpercent probability (Number)
All Eligible Patients (Combination Chemotherapy)92.0

[back to top]

Percentage of Patients With Responses at 189 Days

The percentage of patients with complete response (CR) at the end of induction (~189 days) was reported and presented with the associated exact 95% confidence interval. (NCT02017964)
Timeframe: 189 days from start of treatment

InterventionPercentage of patients (Number)
All Eligible Patients (Combination Chemotherapy)92.0

[back to top]

Percentage of Patients With Responses at 273 Days

The percentage of patients with complete response (CR) at the end of therapy (~273 days) was reported and presented with the associated exact 95% confidence interval. (NCT02017964)
Timeframe: 273 days from start of treatment

InterventionPercentage of patients (Number)
All Eligible Patients (Combination Chemotherapy)88.0

[back to top]

Progression-free Survival (PFS)

Progression-free survival (PFS) is defined as the time interval from diagnosis to the earliest of disease progression/recurrence or death from any cause, or to the date of last follow-up for patients without events. PFS was estimated using the method of Kaplan and Meier. 2-year estimates are reported with 95% CI's. (NCT02017964)
Timeframe: 2 years from diagnosis

Interventionpercent probability (Number)
All Eligible Patients (Combination Chemotherapy)52.0

[back to top]

Safety of DC Vaccine Combined With Chemotherapy

Toxicities will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 . This will include all patients (eligible and ineligible) who receive at least 1 inoculation of DC vaccine therapy. This safety population will also be used for the summaries and analysis of all safety parameters (drug exposure, tables of adverse events information, including serious adverse events, etc.). (NCT02018458)
Timeframe: 4 years

InterventionParticipants (Count of Participants)
LA TNBC: DC Vaccine+Preop Chemo10

[back to top]

Disease-free Survival

"Results are only reported for Arm 1, LA TNBC: DC vaccine+preop chemo patients. Arm 2, ER+/HER2- BC: DC vaccine+preop chemo patients did not enroll any patients with these hormone receptor criteria.~Analysis of disease-free survival (DFS, reported in months) was calculated from the first day of treatment up to 36 months." (NCT02018458)
Timeframe: 36 months

Interventionmonths (Mean)
LA TNBC: DC Vaccine+Preop Chemo15.6

[back to top]

Part 3: Tmax of Parsaclisib Monotherapy

tmax is defined as the time to the maximum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,
Interventionhours (Median)
Cycle 1 Day 1, Cohort ACycle 1 Day 15, Cohort ACycle 1 Day 1, Cohort BCycle 1 Day 15, Cohort BCycle 1 Day 1, Cohort CCycle 1 Day 15, Cohort CCycle 1 Day 1, Cohort DCycle 1 Day 15, Cohort D
Parsaclisib 20 mg QD0.51.02.00.50.51.01.00.5
Parsaclisib 30 mg QD1.01.01.50.751.00.50.751.0

[back to top]

Part 3: Cmin of Parsaclisib Monotherapy

Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,
Interventionnmol (Mean)
Cycle 1 Day 15, Cohort ACycle 1 Day 15, Cohort BCycle 1 Day 15, Cohort CCycle 1 Day 15, Cohort D
Parsaclisib 20 mg QD214395197202
Parsaclisib 30 mg QD281296477421

[back to top]

Part 3: Cmax of Parsaclisib Monotherapy

Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,
Interventionnmol (Mean)
Cycle 1 Day 1, Cohort ACycle 1 Day 15, Cohort ACycle 1 Day 1, Cohort BCycle 1 Day 15, Cohort BCycle 1 Day 1, Cohort CCycle 1 Day 15, Cohort CCycle 1 Day 1, Cohort DCycle 1 Day 15, Cohort D
Parsaclisib 20 mg QD15501720120019301760206017601600
Parsaclisib 30 mg QD23502390172022601760392025002990

[back to top]

Part 3: AUC0-τ of Parsaclisib Monotherapy

AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours [q12h] administration or from hour 0 to 24 for once every 24 hours [q24h] administration) of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,
Interventionhr*nmol/L (Mean)
Cycle 1 Day 15, Cohort ACycle 1 Day 15, Cohort BCycle 1 Day 15, Cohort CCycle 1 Day 15, Cohort D
Parsaclisib 20 mg QD12600179001420013600
Parsaclisib 30 mg QD19500201002800025200

[back to top]

Part 3: AUC0-t of Parsaclisib Monotherapy

AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of of parsaclisib. PK samples for parsaclisib monotherapy were collected and analyzed from the Part 3 dose expansion (different participant populations). Cohort A: B-cell malignancies; Cohort B: Hodgkin's lymphoma; Cohort C: diffuse large B-cell lymphoma; Cohort D: indolent lymphoma. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,
Interventionhr*nmol/L (Mean)
Cycle 1 Day 1, Cohort ACycle 1 Day 1, Cohort BCycle 1 Day 1, Cohort CCycle 1 Day 1, Cohort D
Parsaclisib 20 mg QD6530701071107230
Parsaclisib 30 mg QD107008430120009970

[back to top]

Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT

CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 44 months (3.7 years)

Interventionpercentage of participants (Number)
Diffuse large B-cell lymphomaFollicular lymphomaMantle cell lymphomaClassical Hodgkin's lymphoma
Parsaclisib 20 mg + Itacitinib 300 mg0.00.0100.050.0

[back to top]

Part 2: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT

CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 44 months (3.7 years)

Interventionpercentage of participants (Number)
Diffuse large B-cell lymphoma
Parsaclisib 30 mg + Itacitinib 300 mg0.0

[back to top]

Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT

CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

Interventionpercentage of participants (Number)
Diffuse large B-cell lymphomaFollicular lymphomaMantle cell lymphomaMarginal zone lymphomaNodal marginal zone B-cell lymphomaSplenic marginal zone lymphomaClassical Hodgkin's lymphomaNodular lymphocytic-predominant Hodgkin's lymphoma
Parsaclisib 30 mg QD16.740.0100.00.0100.0100.00.00.0

[back to top]

Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT

CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

Interventionpercentage of participants (Number)
Diffuse large B-cell lymphomaFollicular lymphomaMantle cell lymphomaExtranodal marginal zone lymphoma of mucosa-associated lymphatic tissueNodal marginal zone B-cell lymphomaSplenic marginal zone lymphomaClassical Hodgkin's lymphoma
Parsaclisib 20 mg QD36.485.766.750.0100.0100.050.0

[back to top]

Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT

CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

Interventionpercentage of participants (Number)
Diffuse large B-cell lymphomaMantle cell lymphoma
Parsaclisib 45 mg QD50.00.0

[back to top]

Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT

CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

,
Interventionpercentage of participants (Number)
Diffuse large B-cell lymphomaFollicular lymphoma
Parsaclisib 10 mg QD0.0100.0
Parsaclisib 15 mg QD50.0100.0

[back to top]

Part 1: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for Hodgkin's Lymphoma (HL) and Non-Hodgkin's Lymphoma (NHL), Using Positron Emission Tomography-computed Tomography (PET-CT) and CT

CR, PET-CT: (a) complete metabolic response (MR); (b) lymph nodes and extralymphatic sites (LNs/ELSs): score 1, 2, or 3, with/without residual mass; (c) no new lesions (NNLs); (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

Interventionpercentage of participants (Number)
Diffuse large B-cell lymphoma
Parsaclisib 5 mg QD0.0

[back to top]

Tmax of Itacitinib in Combination With Parsaclisib

tmax is defined as the time to the maximum concentration of itacitinib. (NCT02018861)
Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Interventionhours (Median)
Parsaclisib 20/30 mg + Itacitinib 300 mg2.0

[back to top]

Part 2: Overall Response Rate (Percentage of Participants With CR and PR) Based on IWCLL Criteria for CLL for Participants With CLL

CR: (a) peripheral blood lymphocytes <4 x 10^9/L; (b) no significant lymphadenopathy and lymph nodes <1.5 cm in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10^9/L; (f) platelets ≥100 x 10^9/L; (g) hemoglobin ≥11.0 g/dL (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10^9/L or increase ≥50% over Baseline; (b) ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules. (NCT02018861)
Timeframe: Up to approximately 44 months (3.7 years)

Interventionpercentage of participants (Number)
Parsaclisib 20 mg + Itacitinib 300 mg100.0

[back to top]

Part 1: ORR Based on the VIth International Workshop on Waldenström Macroglobulinemia (WM) Response Assessment for Participants With WM

ORR: sum of participants achieving minor response (MR), PR, very good partial response (VGPR), and CR. CR: (a) no serum monoclonal IgM protein by immunofixation; (b) normal serum IgM level; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at Baseline (BL); (d) morphologically normal bone marrow aspirate and trephine biopsy. VGPR: (a) detectable monoclonal IgM protein; (b) ≥90% reduction in serum IgM level from BL; (c) complete resolution of extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. PR: (a) detectable monoclonal IgM protein; (b) ≥50% but <90% reduction in serum IgM level from BL; (c) reduction in extramedullary disease, i.e., lymphadenopathy/splenomegaly if present at BL; (d) no new signs/symptoms of active disease. MR: (a) detectable monoclonal IgM protein; (b) ≥25% but <50% reduction in serum IgM level from BL; (d) no new signs/symptoms of active disease. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

Interventionpercentage of participants (Number)
Parsaclisib 20 mg QD100.0

[back to top]

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) is defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occur after a participant provides informed consent. Abnormal laboratory values or test results occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, are considered clinically meaningful, require therapy (e.g., hematologic abnormality that requires transfusion), or require changes in the study drug(s). A TEAE is defined as an event that was reported for the first time, or the worsening of a pre-existing event, after the first dose of study drug. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

InterventionParticipants (Count of Participants)
Parsaclisib 5 mg QD1
Parsaclisib 10 mg QD3
Parsaclisib 15 mg QD3
Parsaclisib 20 mg QD32
Parsaclisib 30 mg QD25
Parsaclisib 45 mg QD4
Parsaclisib 20 mg + Itacitinib 300 mg6
Parsaclisib 30 mg + Itacitinib 300 mg3
Parsaclisib 15 mg QD + R-ICE4
Parsaclisib 20 mg QD + R-ICE1

[back to top]

Cmin of Itacitinib in Combination With Parsaclisib

Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of itacitinib. (NCT02018861)
Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Interventionnmol (Mean)
Parsaclisib 20/30 mg + Itacitinib 300 mg32.8

[back to top]

Cmax of Itacitinib in Combination With Parsaclisib

Cmax is defined as the maximum observed plasma or serum concentration of itacitinib. (NCT02018861)
Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Interventionnanomoles (nmol) (Mean)
Parsaclisib 20/30 mg + Itacitinib 300 mg887

[back to top]

AUC0-τ of Itacitinib in Combination With Parsaclisib

AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for once every 12 hours [q12h] administration or from hour 0 to 24 for once every 24 hours [q24h] administration) of itacitinib. (NCT02018861)
Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Interventionhr*nmol/L (Mean)
Parsaclisib 20/30 mg + Itacitinib 300 mg6450

[back to top]

AUC0-t of Itacitinib in Combination With Parsaclisib

AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of itacitinib. (NCT02018861)
Timeframe: Cycle 1 Day 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

Interventionhours (hr)*nmol/L (Mean)
Parsaclisib 20/30 mg + Itacitinib 300 mg6450

[back to top]

Part 1: Overall Response Rate (Percentage of Participants With Complete Response [CR] and Partial Response [PR]) Based on International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Criteria for Chronic Lymphocytic Leukemia (CLL) for CLL Participants

CR: (a) peripheral blood lymphocytes <4 x 10^9/Liter (L); (b) no significant lymphadenopathy and lymph nodes <1.5 centimeters (cm) in longest diameter; (c) no splenomegaly/hepatomegaly; (d) no disease-related constitutional symptoms; (e) neutrophils ≥1.5 x 10^9/L; (f) platelets ≥100 x 10^9/L; (g) hemoglobin ≥11.0 grams/deciliter (g/dL) (without transfusion); (h) minimal residual disease assessment; (i) normocellular marrow, with no CLL cells/no B-lymphoid nodules. PR (improvement in ≥2 Group A parameters and ≥1 Group B parameter if previously abnormal. If only 1 parameter of both Groups A and B was abnormal before therapy, only 1 needs to improve): Group A: (a) decrease of ≥50% (from Baseline) in lymph nodes, liver/spleen size, and circulating lymphocyte count; (b) any constitutional symptoms. Group B: (a) platelets ≥100 x 10^9/L or increase ≥50% over Baseline; (b) hemoglobin ≥11 g/dL or increase ≥50% over Baseline; (c) presence of CLL cells or B-lymphoid nodules. (NCT02018861)
Timeframe: Up to approximately 53 months (4.4 years)

Interventionpercentage of participants (Number)
Parsaclisib 10 mg QD0.0
Parsaclisib 20 mg QD0.0
Parsaclisib 30 mg QD66.7
Parsaclisib 45 mg QD0.0

[back to top]

Parts 1 and 2: Tmax of Parsaclisib as Monotherapy and in Combination With Itacitinib

tmax is defined as the time to the maximum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,,,,,,,
Interventionhours (Median)
Cycle 1 Day 1Cycle 1 Day 15
Parsaclisib 10 mg QD1.01.0
Parsaclisib 15 mg QD1.01.0
Parsaclisib 20 mg + Itacitinib 300 mg1.01.0
Parsaclisib 20 mg QD1.01.0
Parsaclisib 30 mg + Itacitinib 300 mg1.01.0
Parsaclisib 30 mg QD0.50.5
Parsaclisib 45 mg QD1.00.5
Parsaclisib 5 mg QD2.00.5

[back to top]

Parts 1 and 2: Cmin of Parsaclisib as Monotherapy and in Combination With Itacitinib

Cmin is defined as the minimum observed plasma or serum concentration over the dose interval of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,,,,,,,
Interventionnmol (Mean)
Cycle 1 Day 15
Parsaclisib 10 mg QD104
Parsaclisib 15 mg QD156
Parsaclisib 20 mg + Itacitinib 300 mg515
Parsaclisib 20 mg QD178
Parsaclisib 30 mg + Itacitinib 300 mg341
Parsaclisib 30 mg QD295
Parsaclisib 45 mg QD864
Parsaclisib 5 mg QD127

[back to top]

Parts 1 and 2: Cmax of Parsaclisib as Monotherapy and in Combination With Itacitinib

Cmax is defined as the maximum observed plasma or serum concentration of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,,,,,,,
Interventionnmol (Mean)
Cycle 1 Day 1Cycle 1 Day 15
Parsaclisib 10 mg QD791856
Parsaclisib 15 mg QD8081310
Parsaclisib 20 mg + Itacitinib 300 mg17402390
Parsaclisib 20 mg QD12701280
Parsaclisib 30 mg + Itacitinib 300 mg20402500
Parsaclisib 30 mg QD32703310
Parsaclisib 45 mg QD40105530
Parsaclisib 5 mg QD354690

[back to top]

Parts 1 and 2: AUC0-τ of Parsaclisib as Monotherapy and in Combination With Itacitinib

AUC0-τ is defined as the area under the steady-state plasma or serum concentration-time curve over 1 dose interval (i.e., from hour 0 to 12 for q12h administration or from hour 0 to 24 for q24h administration) of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,,,,,,,
Interventionhr*nmol/L (Mean)
Cycle 1 Day 15
Parsaclisib 10 mg QD6910
Parsaclisib 15 mg QD11100
Parsaclisib 20 mg + Itacitinib 300 mg22400
Parsaclisib 20 mg QD11900
Parsaclisib 30 mg + Itacitinib 300 mg22900
Parsaclisib 30 mg QD24800
Parsaclisib 45 mg QD47700
Parsaclisib 5 mg QD7130

[back to top]

Parts 1 and 2: AUC0-t of Parsaclisib as Monotherapy and in Combination With Itacitinib

AUC0-t is defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of parsaclisib. PK samples collected in Part 2, the combination dose escalation study, and in Part 3, Cohort E expansion group, were analyzed for both parsaclisib and itacitinib. (NCT02018861)
Timeframe: Cycle 1 Days 1 and 15; pre-dose and 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

,,,,,,,
Interventionhr*nmol/L (Mean)
Cycle 1 Day 1
Parsaclisib 10 mg QD3260
Parsaclisib 15 mg QD3730
Parsaclisib 20 mg + Itacitinib 300 mg7540
Parsaclisib 20 mg QD5990
Parsaclisib 30 mg + Itacitinib 300 mg10400
Parsaclisib 30 mg QD13300
Parsaclisib 45 mg QD16800
Parsaclisib 5 mg QD2110

[back to top]

Part 6: ORR (Sum of Participants With CR and PR) Based on the Revised Response Criteria for HL and NHL, Using PET-CT and CT

CR, PET-CT: (a) complete MR; (b) LNs/ELSs: score 1, 2, or 3, with/without residual mass; (c) NNLs; (d) no evidence of fluorodeoxyglucose-avid disease in marrow. CT: complete radiologic response: (a) regression of target nodes/nodal masses to ≤ 1.5 cm in longest transverse lesion diameter; (b) no ELSs of disease; (c) absence of nonmeasured lesions; (d) regression to normal organ size; (e) NNLs; (f) normal morphological bone marrow. PR, PET-CT: (a) partial MR; (b) LNs/ELSs: score 4 or 5, with reduced uptake compared with Baseline and residual mass of any size; (c) NNLs; (d) residual uptake higher than uptake in normal marrow but reduced compared with Baseline. CT: partial remission: (a) LNs/ELSs: ≥ 50% decrease in the sum of the product of the perpendicular diameters for multiple lesions of up to 6 target measurable sites; (b) spleen must have regressed by > 50% in length beyond normal; (c) NNLs. (NCT02018861)
Timeframe: Up to approximately 4 months

,
Interventionpercentage of participants (Number)
Diffuse large B-cell lymphoma
Parsaclisib 15 mg QD + R-ICE50.0
Parsaclisib 20 mg QD + R-ICE100.0

[back to top]

Time to Confirmed Response During Induction and Over the Entire Study

Time to confirmed complete or partial response (CR/PR) is defined as the time from day 1 of treatment in Induction to the first occurrence of confirmed CR/PR. Two timeframes are offered: - Time to confirmed response within the Induction timeframe. - Time to Confirmed Response Over the Entire Study, i.e. the time from Day 1 of treatment in Induction to the first occurrence of confirmed CR/PR any time during the study. Only participants with a confirmed CR or PR are included in this summary. (NCT02027428)
Timeframe: Induction is from Day 1 to a maximum treatment time of 19 weeks; entire study from Day 1 Induction through Maintenance up to PD; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study

Interventionmonths (Median)
All Participants - Induction1.446
Nab-Paclitaxel + BSC: Induction + Maintenance1.478
BSC: Induction + Maintenance1.413

[back to top]

Participants With Treatment-Emergent Adverse Events (TEAEs) Over the Entire Study

TEAE over entire study is defined as any adverse event (AE) with an onset on or after Day 1 of treatment for the Induction part, and before the treatment discontinuation date plus 28 days, or any serious AE which occurred thereafter but was determined to be related to any study drug by the investigator. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life threatening, Grade 5 = Death. Relation to study drug was determined by the investigator. (NCT02027428)
Timeframe: From Day 1 up to 01 August 2019; (maximum treatment length plus 28 days); the maximum treatment duration was 234.1 weeks for entire study

,,,,,,,
InterventionParticipants (Count of Participants)
TEAESerious TEAESeverity Grade 3/4 TEAESeverity Grade 3 or higher TEAETreatment-related (trt-related) TEAETrt-related serious TEAETEAE-study drug dose reduced or interruptedTrt-related TEAE-dose reduced or interruptedTEAE-study drug withdrawnTrt-related TEAE- study drug withdrawnTEAE-outcome of deathTrt-related TEAE-outcome of death
BSC: Induction + Maintenance6221484861852450120
BSC: TEAE Specific to BSCNANANANA101000NA0
BSC: TEAE Specific to CarboplatinNANANANA587453710NA0
BSC: TEAE Specific to Nab-PaclitaxelNANANANA618524510NA0
Nab-Paclitaxel + BSC: Induction + Maintenance1305410810912922115107221840
Nab-Paclitaxel + BSC: TEAE Specific to BSCNANANANA181170202NA0
Nab-Paclitaxel + BSC: TEAE Specific to CarboplatinNANANANA12316958511NA0
Nab-Paclitaxel + BSC: TEAE Specific to Nab-PaclitaxelNANANANA129221131042218NA0

[back to top]

Participants With Treatment-Emergent Adverse Events (TEAEs) in the Induction Period

TEAE in the Induction part is defined as any adverse event (AE) with an onset on or after Day 1 of treatment for the Induction part, and on or before the day of randomization for subjects who entered into the Maintenance part, or, for subjects who did not enter into the Maintenance part, before the treatment discontinuation date plus 28 days or any serious AE which occurred thereafter but was determined to be related to any study drug by the investigator. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild, Grade 2 = Moderate Grade, 3 = Severe Grade, 4 = Life threatening, Grade 5 = Death. Relation to study drug was determined by the investigator. (NCT02027428)
Timeframe: Day 1 of Induction up to Week 23 (maximum treatment in Induction plus 4 weeks if not continuing into Maintenance)

,,
InterventionParticipants (Count of Participants)
TEAESerious TEAESeverity Grade 3/4 TEAESeverity Grade 3 or higher TEAETreatment-related (trt-related) TEAETrt-related serious TEAETEAE-study drug dose reduced or interruptedTrt-related TEAE-dose reduced or interruptedTEAE-study drug withdrawnTrt-related TEAE-study drug withdrawnTEAE-outcome of deathTrt-related TEAE-outcome of death
All Participants - Induction419177337340408823413015535327
TEAE Specific to CarboplatinNANANANA394732912365329NA6
TEAE Specific to Nab-PaclitaxelNANANANA407803402925534NA7

[back to top]

Percentage of Participants Who Achieved Disease Control (Disease Control Rate) by Investigator Assessment During Induction and Over the Entire Study

Disease control rate was defined as the percentage of participants who had radiologic CR, PR or SD for >= 6 weeks according to RECIST 1.1 criteria as determined by the investigator. Only participants with a confirmed CR/PR are included in this summary. Two timeframes are offered: - Time to confirmed response within the Induction timeframe. - Time to Confirmed Response Over the Entire Study, i.e. the time from Day 1 of treatment in Induction to the first occurrence of confirmed CR/PR any time during the study. RECIST 1.1 Definition: - CR- disappearance of all target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to < 10 mm. - PR- at least a 30% decrease in the sum of diameters of target lesions from baseline; - SD- neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for PD. The 95% CI was calculated using Clopper-Pearson method. (NCT02027428)
Timeframe: Induction is from Day 1 to a maximum treatment time of 19 weeks; entire study from Day 1 induction through maintenance up to PD; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study

Interventionpercentage of participants (Number)
All Participants - Induction47.9
Nab-Paclitaxel + BSC: Induction + Maintenance99.3
BSC: Induction + Maintenance100.0

[back to top]

Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) Over Entire Study

Overall response was defined as the percentage of participants with a confirmed assessment of complete response (CR) or partial response (PR) according to RECIST 1.1 criteria and confirmed in no less than 28 days. The 95% confidence interval (CI) was calculated using Clopper-Pearson method. RECIST 1.1 Definition: - Complete response-disappearance of all target lesions; any pathological lymph nodes (whether target or non target) must have reduction in short axis to < 10 mm. - Partial response-at least a 30% decrease in the sum of diameters of target lesions from baseline. (NCT02027428)
Timeframe: Day 1 of treatment in the induction period and subsequent anticancer therapy, death or discontinuation up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study

Interventionpercentage of participants (Number)
Nab-Paclitaxel + BSC: Induction + Maintenance69.1
BSC: Induction + Maintenance57.6

[back to top]

Percentage of Participants Who Achieved a Confirmed Overall Response of Complete Response or Partial Response (Overall Response Rate) In Maintenance Beyond the Response in Induction

Overall response in the maintenance period was defined as the percentage of participants who showed an improvement in best overall response from stable disease (SD) or partial response (PR) during Induction to a Complete Response (CR) or PR during Maintenance according to RECIST 1.1 criteria and confirmed in no less than 28 days. Evaluation takes as reference the lesion measurement or status at the last tumor assessment before randomization to Maintenance. The 95% CI was calculated using Clopper-Pearson method. RECIST 1.1 Definition: - Complete response-disappearance of all target lesions; any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. - Partial response-at least a 30% decrease in the sum of diameters of target lesions from baseline. - Stable disease-neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease. (NCT02027428)
Timeframe: For the induction period the maximum treatment was 19 weeks for the maintenance period the maximum treatment was 150 weeks.

Interventionpercentage of participants (Number)
Nab-Paclitaxel + BSC: Induction + Maintenance9.6
BSC: Induction + Maintenance3.0

[back to top]

Kaplan-Meier Estimate of Progression-Free Survival (PFS) Over Entire Study

PFS was defined as the time in months from Day 1 of treatment for the Induction part to the date of disease progression according to RECIST 1.1 criteria (documented by CT-scan, not including symptomatic deterioration) or death (any cause) on or prior to 01 August 2019, whichever occurred earlier. RECIST 1.1 Definition: - Progressive Disease (PD) - At least a 20% increase in the sum of diameters of target lesions from nadir; the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of new lesions is also considered progression. (NCT02027428)
Timeframe: Between Day 1 of the Induction Part through to the date of disease progression or death; up to 01 August 2019; the maximum treatment duration was 234.1 weeks for entire study

Interventionmonths (Median)
Nab-Paclitaxel + BSC: Induction + Maintenance6.47
BSC: Induction + Maintenance5.55

[back to top]

Kaplan-Meier Estimate of Progression-Free Survival (PFS) From Randomization Into Maintenance

Progression-free survival is defined as the time in months from the date of randomization to the date of disease progression based on the investigator's assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by computerized axial tomography [CT scan], not including symptomatic deterioration) or death (any cause) on or prior to 01 Aug 2019. RECIST 1.1 Definition: - Complete response (CR) -disappearance of all target lesions; - Partial response (PR) -at least a 30% decrease in the sum of diameters of target lesions from baseline - Stable disease (SD) -neither sufficient shrinkage to qualify for partial response (PR) nor sufficient increase of lesions to qualify for progressive disease (PD) - Progressive Disease (PD) - At least a 20% increase in the sum of diameters of target lesions from nadir, and/or the appearance of new lesions. (NCT02027428)
Timeframe: From the date of randomization to the date of disease progression or death of any cause; up to data cut off date of 15 September 2017; up to 27.6 months

Interventionmonths (Median)
Nab-Paclitaxel + Best Supportive Care (BSC)3.12
Best Supportive Care (BSC)2.60

[back to top]

Kaplan-Meier Estimate of Overall Survival (OS) Over Entire Study

Overall survival was defined as the time in months from Day 1 of treatment for the Induction part to death from any cause. Subjects who were alive at the time of analysis had their OS censored at the date or last contact of 01 August 2019, whichever was earlier. The last contact date was the date of the last record in the database, or if the subject was lost to follow-up, the last known date that the subject was alive. (NCT02027428)
Timeframe: Between Day 1 of treatment in the Induction Part to death from any cause; up to 01 August 2019; survival follow up was 55.89 months

Interventionmonths (Median)
Nab-Paclitaxel + BSC: Induction + Maintenance20.57
BSC: Induction + Maintenance15.05

[back to top]

Kaplan-Meier Estimate of Overall Survival (OS) From Randomization Into Maintenance

Overall survival was defined as the duration in months between randomization and death from any cause. Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off (01 August 2019 whichever was earlier. The last contact date was the date of the last record in the database, or if the subject was lost to follow-up, the last known date that the subject was alive. (NCT02027428)
Timeframe: From the date of randomization to death from any cause; up to 01 August 2019; survival follow up was 55.89 months

Interventionmonths (Median)
Nab-Paclitaxel + Best Supportive Care (BSC)17.61
Best Supportive Care (BSC)12.16

[back to top]

Kaplan-Meier Estimate for Duration of Response Over the Entire Study

Duration of overall response was measured from the time criteria were first met for CR/PR until the first date the recurrent or progressive disease (PD) was radiologically documented. Participants who did not have PD after the response were censored on the date of last tumor assessment. If a participant died before PD, the participant was censored on the date of death. (NCT02027428)
Timeframe: Between Day 1 of the Induction Period through to the date of disease progression or death; up to 01 August 2019; maximum treatment duration was 234.1 weeks for entire study.

Interventionmonths (Median)
Nab-Paclitaxel + BSC: Induction + Maintenance5.95
BSC: Induction + Maintenance4.60

[back to top]

Number of Participants With Carboplatin Infusion Hypersensitivity Reactions Using a Slowed Carboplatin Infusion Program

To determine the frequency of carboplatin infusion hypersensitivity reactions using a slowed carboplatin infusion program (NCT02035345)
Timeframe: 2 Years

Interventionparticipants (Number)
Carboplain Slowed Infusion Group Reactors6

[back to top]

Number of Patients With Carboplatin Reactions of Different Severity

To characterize the nature and symptoms of carboplatin reactions associated with the slowed infusion protocol. (NCT02035345)
Timeframe: 2 Years

Interventionparticipants (Number)
Grade 2Grade 3Grade 4
Carboplatin321

[back to top]

Part 2 Cohorts G+ and G-: Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. (NCT02039674)
Timeframe: Up to approximately 2 years

InterventionMonths (Median)
Part 2 Cohort G+ (Pembro 200 mg+Pe+C)34.5
Part 2 Cohort G- (Placebo+Pe+C)21.1

[back to top]

Part 2 Cohorts G+ and G-: Objective Response Rate (ORR)

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR). (NCT02039674)
Timeframe: Up to approximately 2 years

InterventionPercentage of Participants (Number)
Part 2 Cohort G+ (Pembro 200 mg+Pe+C)55.0
Part 2 Cohort G- (Placebo+Pe+C)28.6

[back to top]

Part 2 Cohorts G+ and G-: Duration of Response (DOR)

For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR. (NCT02039674)
Timeframe: Up to approximately 2 years

InterventionMonths (Median)
Part 2 Cohort G+ (Pembro 200 mg+Pe+C)NA
Part 2 Cohort G- (Placebo+Pe+C)NA

[back to top]

Part 2 Cohorts D4 and H: Objective Response Rate (ORR)

For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. Per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR was assessed by BICR. (NCT02039674)
Timeframe: Up to approximately 2 years

InterventionPercentage of Participants (Number)
Part 2 Cohorts D4 & H (Pembro 2mg/kg+I)29.5

[back to top]

All Cohorts: Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

DLTs were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4. A DLT was defined as any of the following events: Grade 4 non-hematologic toxicity (not laboratory); Grade 4 hematologic toxicity lasting ≥7 days; Grade 3 non-hematologic toxicity (not laboratory, specifically nausea, vomiting and diarrhea) lasting >3 days despite optimal supportive care; Any Grade 3 or Grade 4 non-hematologic laboratory value requiring treatment or hospitalization, or persisting for >1 week; Febrile neutropenia Grade 3 or Grade 4; Qualifying thrombocytopenia <25,000/mm^3; Prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity; Missing >10% of erlotinib or gefitinib doses as a result of adverse events (AEs) during the DLT window of observation; or Grade 5 toxicity. (NCT02039674)
Timeframe: Cycle 1 (Up to 21 days)

InterventionParticipants (Count of Participants)
Part1 Cohort A2 (Pembro 2 mg/kg+Paclitaxel [Pa]+Carboplatin [C])0
Part1 Cohort A10 (Pembro10mg/kg+Pa+C)0
Part 1 Cohort B2 (Pembro 2mg/kg+Pa+C+Bevacizumab [B])0
Part 1 Cohort B10 (Pembro 10 mg/kg+Pa+C+B)0
Part 1 Cohort C2 (Pembro 2 mg/kg+Pemetrexed [Pe]+C)0
Part 1 Cohort C10 (Pembro 10 mg/kg+Pe+C)0
Part 1 Cohort D1 (Pembro 10mg/kg+Ipilimumab [I])0
Part 1 Cohort D2 (Pembro 10 mg/kg+I)0
Part 1 Cohort D4 (Pembro 2 mg/kg+I)0
Part 1 Cohort E (Pembro 2 mg/kg+Erlotinib)0
Part 1 Cohort F (Pembro 2 mg/kg+Gefitinib)0
Part 2 Cohort G+ (Pembro 200 mg+Pe+C)0
Part 2 Cohort G- (Placebo+Pe+C)0
Part 2 Cohort H (Pembro 2 mg/kg+I)0

[back to top]

Part 2 Cohorts G+ and G-: Progression-Free Survival (PFS)

PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. PFS was assessed by BICR. (NCT02039674)
Timeframe: Up to approximately 2 years

InterventionMonths (Median)
Part 2 Cohort G+ (Pembro 200 mg+Pe+C)24.5
Part 2 Cohort G- (Placebo+Pe+C)9.9

[back to top]

Progression-Free Survival in Participants With PD-L1 Expression >= 5%

Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy. (NCT02041533)
Timeframe: From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)

InterventionMonths (Median)
Nivolumab4.21
Investigator Choice of Chemotherapy5.88

[back to top]

Progression-Free Survival in All Randomized Participants

Progression-Free Survival (PFS) was defined as the time between the date of randomization and the first date of documented tumor progression, as determined by the Independent Radiology Review Committee (IRRC) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death due to any cause, whichever occurs first. Participants who die without a reported progression were considered to have progressed on the date of their death. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the day they were randomized. Participants who received subsequent anti-cancer therapy prior to documented progression were censored at the last evaluable tumor assessment prior to the initiation of new therapy. (NCT02041533)
Timeframe: From date of randomization until date of documented tumor progression (assessed up to August 2016, approximately 28 months)

InterventionMonths (Median)
Nivolumab4.21
Investigator Choice of Chemotherapy5.82

[back to top]

Objective Response Rate (ORR) in Participants With PD-L1 Expression >= 5%

ORR was defined as the proportion of randomized participants who achieved a Best Overall Response (BOR) of CR or PR using the RECIST v1.1 criteria per Independent Radiology Review Committee (IRRC) assessment. BOR was defined as the best response designation recorded between the date of randomization and the date of objectively documented progression or start of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or subsequent therapy, all available response designations contributed to the BOR assessment. For participants who continued treatment beyond progression, BOR was determined from response designations recorded up to the time of initial progression. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measureable disease and no new sites; Stable Disease (SD)= Failure to attain CR/PR or PD; Progressive Disease (PD)= Any new lesion or increase by >=50% of previously involved sites from nadir. (NCT02041533)
Timeframe: From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to August 2016, approximately 28 months)

InterventionPercentage of participants (Number)
Nivolumab26.1
Investigator Choice of Chemotherapy33.5

[back to top]

Overall Survival in All Randomized Participants

Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up. (NCT02041533)
Timeframe: From date of randomization to date of death (up to approximately 89 months)

InterventionMonths (Median)
Nivolumab13.73
Investigator Choice of Chemotherapy13.80

[back to top] [back to top]

Overall Survival in Participants With PD-L1 Expression >= 5%

Overall Survival (OS) was defined as the time from randomization to the date of death. A participant who had not died was censored at the last known alive date. OS was censored at the date of randomization for participants who were randomized but had no follow-up. (NCT02041533)
Timeframe: From date of randomization to date of death (up to approximately 89 months)

InterventionMonths (Median)
Nivolumab14.36
Investigator Choice of Chemotherapy13.21

[back to top]

Level of Obesity

Obesity will be quantitative assessed by body mass index (BMI) and will be assessed for its predictive and prognostic significance. The interaction between BMI and metformin treatment will be examined with an interaction term in a Cox proportional hazards model. (NCT02065687)
Timeframe: Up to 5 years

Interventionproportion of participants obese (Number)
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)0.4957
Arm II (Paclitaxel, Carboplatin, Placebo)0.4979

[back to top]

Duration of Response by Treatment

Duration of response until disease progression, death, or date last seen among patients who responded. (NCT02065687)
Timeframe: From the date of response to disease progression, death, or date last seen assessed up to 5 years

InterventionMonths (Median)
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)8.0
Arm II (Paclitaxel, Carboplatin, Placebo)8.0

[back to top]

Number of Participants With Grade 3 or Higher Adverse Events as Assessed by Common Terminology Criteria for Adverse Events Version 4

Toxicities will be assessed by organ or organ system. For each category of toxicity, each patient will be evaluated by the worst grade experienced during the course of therapy. Data will be summarized by frequency and severity according to the regimen administered. The number of patients with a grade three or greater adverse event will be reported (by system organ class). (NCT02065687)
Timeframe: Up to 5 years

,
InterventionParticipants (Count of Participants)
Blood and lymphatic system disordersCardiac disordersEar and labyrinth disordersEndocrine disordersEye disordersGastrointestinal disordersGeneral disorders administration site conditionsImmune system disordersInfections and infestationsInjury, poisoning and procedural complicationsInvestigationsMetabolism and Nutrition DisordersMusculoskeletal and connective tissue disordersNeoplasms benign, malignant and unspecifiedNervous system disordersPsychiatric disordersRenal and urinary disordersReproductive system and breast disordersRespiratory, thoracic and mediastinal disordersSkin and subcutaneous tissue disordersVascular disorders
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)23210017501423881180117210
Arm II (Paclitaxel, Carboplatin, Placebo)172000106110628183092504118

[back to top]

Proportion of Patients Responding to Therapy

The proportion of patients who had a response (complete or partial) by RECIST 1.1. Measurable disease is defined by RECIST (version 1.1). Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT, MRI or caliper measurement by clinical exam; or ≥ 20 mm when measured by chest x-ray. Lymph nodes must be > 15 mm in short axis when measured by CT or MRI. (NCT02065687)
Timeframe: During study treatment, up to 5 years.

Interventionpercentage of patients (Number)
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)61.6
Arm II (Paclitaxel, Carboplatin, Placebo)60.2

[back to top]

Progression-free Survival (PFS) (Phase II)

Time until disease progression, death, or date of last contact. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined. (NCT02065687)
Timeframe: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years

InterventionMonths (Median)
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)9.0
Arm II (Paclitaxel, Carboplatin, Placebo)8.5

[back to top]

Progression Free Survival (PFS) (Phase III)

Time until disease progression, death, or date of last contact. For response, only those patients who had measurable disease were included in an analysis of response. Non-measurable patients are included in the ITT analysis. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined. (NCT02065687)
Timeframe: From date of study entry to time of progression or death, whichever occurs first, assessed up to 5 years

InterventionMonths (Median)
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)9.0
Arm II (Paclitaxel, Carboplatin, Placebo)8.5

[back to top]

Overall Survival (OS) (Phase II)

The observed length of life from randomization into the study to death or the date of last contact. For response, only those patients who had measurable disease were included in an analysis of response. Non-measurable patients are included in the ITT analysis. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined. (NCT02065687)
Timeframe: From date of study entry to time of death or the date of last contact, assessed up to 5 years.

InterventionMonths (Median)
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)34.6
Arm II (Paclitaxel, Carboplatin, Placebo)30.4

[back to top]

Overall Survival (OS) (Phase II and III)

The observed length of life from randomization into the study to death or the date of last contact. This study was originally designed as a phase II/III study. It passed the phase 2 threshold and started the phase 3; however, a phase 3 interim analysis stopped the trial for futility. Therefore, data available for Phase III may be identical to data reported for Phase II or Phase II/III combined. (NCT02065687)
Timeframe: From date of study entry to time of death or the date of last contact, assessed up to 5 years

InterventionMonths (Median)
Arm I (Paclitaxel, Carboplatin, Metformin Hydrochloride)34.6
Arm II (Paclitaxel, Carboplatin, Placebo)30.4

[back to top]

Metabolic Response of All Pulmonary Lesions and Thoracic Lymph Nodes

Favorable response will be defined as having maximum SUV less than 6.0 on post-treatment PET/CT. (NCT02073968)
Timeframe: Up to 16 weeks after completion of radiation therapy

InterventionParticipants (Count of Participants)
Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)24

[back to top]

Lung Cancer Cause-specific Survival

"Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions~A patient will be considered to have died from lung cancer if he or she had evidence of disease progression at any site and no direct evidence of other cause of death. Kaplan-Meier survival plots will be produced." (NCT02073968)
Timeframe: From study registration to death directly from lung cancer, censored at the date of data collection, assessed up to 5 years

Interventionmonths (Median)
Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)28

[back to top]

Locoregional Progression-free Survival Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria

"Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions~Kaplan-Meier survival plots will be produced. The survival probabilities will be presented." (NCT02073968)
Timeframe: From study registration to date of local or regional disease progression or death, censored at the date of data collection, assessed up to 5 years

Interventionpercentage with LRPFS at 1 year (Number)
Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)50

[back to top] [back to top]

Progression-free Survival Assessed Using the RECIST Criteria

"Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions~Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for progression free survival among the predictor variables." (NCT02073968)
Timeframe: From study registration to date of disease progression or death, censored at the date of data collection, assessed up to 5 years

Interventionpercentage of patients w/ PFS at 1 year (Number)
Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)26

[back to top]

Incidence of Grade >= 2 Radiation-induced Lung Toxicity, Scored Using Common Terminology Criteria for Adverse Events (CTCAE), Version (v.) 4

Incidence of grade >= 2 radiation-induced lung toxicity, scored using Common Terminology Criteria for Adverse Events (CTCAE), version (v.) 4, will be presented as frequency and percentages. (NCT02073968)
Timeframe: Up to 5 years

InterventionParticipants (Count of Participants)
Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)7

[back to top]

Overall Survival

Kaplan-Meier survival plots will be produced. The survival probabilities will be presented. Log-rank testing will be used to compare the survival probabilities between categorical predictors. A Cox regression model will be used to estimate the hazard rates for overall survival among the predictor variables. (NCT02073968)
Timeframe: From study registration to death, censored at the date of data collection, assessed up to 5 years

Interventionpercentage of patients alive at 1 year (Number)
Treatment (PET-adjusted IMRT, Carboplatin, Paclitaxel)74

[back to top]

Number of Subjects With Treatment-emergent Adverse (TEAEs), Serious TEAEs, TEAEs Leading to Discontinuation and TEAEs Leading to Death

An adverse event (AE) was defined as any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE was any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. AEs were considered treatment emergent if they started on or after the day of first administration of the first trial treatment given (Sym004 or one of the individual Platinum-Doublet therapies) or if they worsened after receiving first dose of treatment. (NCT02083679)
Timeframe: Day 1 up to 28 days after last dose of study drug (up to 53 weeks)

,,,
Interventionsubjects (Number)
TEAEsSerious TEAEsTEAE leading to DiscontinuationTEAEs Leading to Death
Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel3300
Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine3310
Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed6530
Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel3320

[back to top]

Number of Subjects With Dose Limiting Toxicities (DLTs)

DLT: any National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.03 Grade 4 hematologic or Grade 3/4 non-hematologic toxicities that occurred during DLT observation period and were considered by Investigator to be at least possibly related to trial treatment, and were confirmed by Safety Monitoring Committee (SMC), with exception of Grade 4 neutropenia for not >5 days; Grade 4 lymphocytopenia/ thrombocytopenia for not >5 days; fatigue/headache lasting < 7 days; nausea/vomiting/diarrhoea lasting not >3 days; asymptomatic Grade 3 increase in liver function tests that resolve to baseline within 7 days; Mucositis >= Grade 3 lasting < 7 days; Grade 3 hyperglycemia that resolves in < 7 days; any laboratory values >Grade 3 without any clinical correlate (resolve within 5 days); Grade 3 skin toxicities that resolve to Grade 2 within 7 days; Grade 3/4 hypomagnesemia that resolves within 5 days. Subjects with DLTs presented based on investigator and SMC decision. (NCT02083679)
Timeframe: Day 1 to Day 21 of Cycle 1

,,,
InterventionSubjects (Number)
InvestigatorSMC
Part 1: Sym004 6 mg/kg + Carboplatin/Paclitaxel10
Part 1: Sym004 6 mg/kg + Cisplatin/Gemcitabine22
Part 1: Sym004 6 mg/kg + Cisplatin/Pemetrexed11
Part 1: Sym004 6/12 mg/kg + Carboplatin/Paclitaxel00

[back to top]

Assess the Disease Control Rate in Each Treatment Arm

the disease control rate is defined as the percentage of FAS subjects with a best overall response of CR, PR or SD). (NCT02087241)
Timeframe: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

InterventionPercentage of Participants (Number)
Cohort 166.7
Cohort 266.7
Cohort 30
Cohort A85.7

[back to top]

Assess the Objective Response Rates in Each Arm

The objective response rate is defined as the number of the subjects with a confirmed best overall response of CR or PR divided by the number of subjects in the Full Analysis Set (FAS) for whom measureable disease is present at baseline (NCT02087241)
Timeframe: Up to a maximum of 4 treatment cycles (treatment cycles will be repeated every 21 days)

InterventionPercentage of Participants (Number)
Cohort 166.7
Cohort 233.3
Cohort 30
Cohort A14.3

[back to top]

Phase Ib and II: Progression Free Survival (PFS)

"Phase Ib: Progression-free Survival is calculated from date of enrollment to the date of disease progression or death due to any cause, whichever occurs first. Symptomatic deterioration is not considered PD. For a patient without evidence of disease progression or death, Progression-free survival will be censored at the date of last evaluable tumor assessment. Patients with no evaluable tumor assessments will be censored at the date of first study drug administration.~Phase II: Progression-free survival (PFS) based on Blinded Independent Central Review (BICR) is the primary endpoint and is defined as the number of days from the date of randomization to the date of objective disease progression or relapse (according to RECIST v1.1 only) or death due to any cause, whichever occurs first. If neither event occurs, PFS is censored at the date of the last evaluable tumor assessment. Symptomatic deterioration is not considered objective disease progression." (NCT02098343)
Timeframe: Up to 24 months

Interventiondays (Median)
Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.330
Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.277.5
Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.313
Phase II: Arm A. APR-246 + Carboplatin/PLD.283
Phase II: Arm B. Carboplatin/PLD.295

[back to top]

Phase Ib: Dose-limiting Toxicities (DLT) (See Description) of Combined APR-246 and Carboplatin/PLD Regimen

DLT: Hematological and non-hematological toxicities according to grade/days stated in the protocol. (NCT02098343)
Timeframe: Until the end of the first treatment cycle, i.e., Day 28

InterventionParticipants (Count of Participants)
Phase Ib. APR-246 (35mg/kg) + Carboplatin/PLD.0
Phase Ib. APR-246 (50mg/kg) + Carboplatin/PLD.1
Phase Ib. APR-246 (67.5mg/kg) + Carboplatin/PLD.0

[back to top]

Part A: Volume of Distribution (Vz) for MLN4924

(NCT02122770)
Timeframe: Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A

,,,
InterventionLiter (L) (Geometric Mean)
Day 1Day 8
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg494421
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg511550
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg503477
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg445445

[back to top] [back to top] [back to top]

Part A Tmax: Time to Reach the Cmax for MLN4924

(NCT02122770)
Timeframe: Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A

,,,
Interventionhour (Median)
Day 1Day 8
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg1.241.03
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg1.051.13
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg1.041.21
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg1.021.50

[back to top]

Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Fluconazole

(NCT02122770)
Timeframe: Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionh*ng/mL (Geometric Mean)
Part A: MLN4924 8 mg/m^2450
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg498

[back to top]

Part A AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MLN4924 and MLN4924 + Itraconazole

(NCT02122770)
Timeframe: Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionh*ng/mL (Geometric Mean)
Part A: MLN4924 8 mg/m^2465
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg585
Part A: MLN4924 15 mg/m^2798
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg1060
Part A: MLN4924 20 mg/m^21120
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg1130

[back to top]

Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Fluconazole

(NCT02122770)
Timeframe: Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionhour*nanogram per milliliter (h*ng/mL) (Geometric Mean)
Part A: MLN4924 8 mg/m^2445
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg491

[back to top]

Part A AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for MLN4924 and MLN4924 + Itraconazole

(NCT02122770)
Timeframe: Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionh*ng/mL (Geometric Mean)
Part A: MLN4924 8 mg/m^2459
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg571
Part A: MLN4924 15 mg/m^2793
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg1030
Part A: MLN4924 20 mg/m^21110
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg1140

[back to top]

Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Fluconazole

(NCT02122770)
Timeframe: Day 1 (MLN4924) and Day 8 (MLN4924 + Fluconazole): pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Part A: MLN4924 8 mg/m^251.6
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg51.0

[back to top]

Part A Cmax: Maximum Observed Plasma Concentration for MLN4924 and MLN4924 + Itraconazole

(NCT02122770)
Timeframe: Day 1 (MLN4924) and Day 8 (MLN4924 + Itraconazole): pre-dose and at multiple time points (up to 72 hours) post-dose

Interventionng/mL (Geometric Mean)
Part A: MLN4924 8 mg/m^259.1
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg66.8
Part A: MLN4924 15 mg/m^2121
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg193
Part A: MLN4924 20 mg/m^2178
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg137

[back to top]

Part B: Duration of Response

The duration of response was defined in participants with disease response (CR or PR) as the time between the first documentation of response and progressive disease (PD). Responders without PD will be censored at the last clinical assessment of response. CR was defined as complete disappearance of all target lesions. All pathological lymph nodes, both target and non-target, must decrease to normal (short axis <10 mm). PR was defined as at least 30% decrease under baseline of the sum of diameters of all target lesions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (NCT02122770)
Timeframe: Time from the date of first documentation of a response and PD (approximately up Cycle 29)

Interventionmonths (Mean)
Part B: MLN4924 + Docetaxel4.07
Part B: MLN4924 + Carboplatin or Paclitaxel8.46

[back to top]

Part B: Percentage of Participants With Objective Response

Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as complete disappearance of all target lesions. All pathological lymph nodes, both target and non-target, must decrease to normal (short axis less than [<]10 millimeter [mm]). PR was defined as at least 30% decrease under baseline of the sum of diameters of all target lesions. (NCT02122770)
Timeframe: Baseline up to symptomatic deterioration, progressive disease (PD), treatment discontinuation, or until the study is stopped (approximately Cycle 29)

Interventionpercentage of participants (Number)
Part B: MLN4924 + Docetaxel10.5
Part B: MLN4924 + Carboplatin or Paclitaxel22.2

[back to top]

Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) and Serious Adverse Event (SAE)

(NCT02122770)
Timeframe: Baseline up to 30 days after the last dose of study drug (Day 40 for Part A; approximately Cycle 29 for Part B)

,,,,,
InterventionParticipants (Count of Participants)
TEAESAE
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg62
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg185
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg133
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg133
Part B: MLN4924 + Carboplatin or Paclitaxel136
Part B: MLN4924 + Docetaxel2314

[back to top]

Number of Participants With Clinically Significant Change From Baseline in Body Weight Measurements

(NCT02122770)
Timeframe: Part A: Baseline up to Day 40; Part B: Baseline up to approximately Cycle 29

,,,,,
Interventionparticipants (Number)
Grade 1 AE: 5 < 10% decrease from baselineGrade 2 AE: 10 - <20% decrease from baselineGrade 3 AE: >=20% decrease from baseline
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg000
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg110
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg000
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg000
Part B: MLN4924 + Carboplatin or Paclitaxel100
Part B: MLN4924 + Docetaxel100

[back to top]

Part A: Terminal Phase Elimination Half-life (T1/2) for MLN4924

(NCT02122770)
Timeframe: Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A

,,,
Interventionhour (Geometric Mean)
Day 1Day 8
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg9.7411.0
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg9.8810.7
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg11.011.6
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg10.613.3

[back to top]

Part A: Plasma Clearance (CLp) for MLN4924

(NCT02122770)
Timeframe: Days 1 and 8: predose and at multiple time-points (up to 72 hours) postdose for Part A

,,,
Interventionliter per hour (L/h) (Geometric Mean)
Day 1Day 8
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg35.226.5
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg35.835.5
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg31.728.6
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg29.223.2

[back to top]

Part A: Blood to Plasma (B/P) Concentration Ratio for MLN4924

(NCT02122770)
Timeframe: Day 1 up to 24 hours post infusion

,,,
InterventionRatio (Geometric Mean)
End of infusion2 hours post infusion8 hours post infusion24 hours post infusion
Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg55.266.570.766.3
Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg35.148.856.758.0
Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg51.169.271.171.9
Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg43.754.773.767.6

[back to top]

Incidence of Adverse Events

Grade 3 and 4 toxicities associated with this combined chemotherapy regimen as assessed by clinician assessment using the NCI Common Terminology Criteria for Adverse Events,a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care Activities of daily living (ADL). Grade 4 Life-threatening consequences; urgent intervention indicated. Describe patient reported symptoms associated with this regimen. (NCT02124707)
Timeframe: 18 weeks

Interventionincidents (Number)
Small Intestinal ObstructionFatigueGait DisturbanceInfusion Related ReactionSepsisLymphocyte Count DecreasedNeutrophil Count DecreasedPlatelet Count DecreasedWhite Blood Cell DecreasedHypernatremiaHypoalbuminemiaHypomagnesemiaMyalgiaPneumothoraxDry SkinRash Acneiform
Carboplatin, Paclitaxel and Cetuximab1211136171111115

[back to top]

Head and Neck Quality of Life Assessments

Quality of life (QOL) as measured by the Functional Assessment of Cancer Therapy - Head and Neck (FACT-HN) questionnaire. The FACT-HN is the FACT-General (FACT-G) and a head and neck cancer specific, 12 item subscale given at baseline, at end of treatment, and at first follow-up visit. The FACT-G is a 27 item measure of general QOL assessing function in 4 domains: physical well-being (PWB), social-family well-being (SFWB), emotional well-being (EWB) and functional well-being (FWB). Items are rated by patients on a Likert scale from 0 to 4, with all subscales summed to give a total score with a range of 0-148 Higher scores represent better QOL. (NCT02124707)
Timeframe: Baseline, End of treatment (EOT), First follow-up visit (8-12 weeks after EOT)

Interventionscore on a scale (Median)
QOL at BaselineQOL at End of TreatmentQOL at First Follow-up
Carboplatin, Paclitaxel and Cetuximab92.58788

[back to top]

Median Progression Free Survival

Progression events will be defined per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions Progression free survival after treatment with weekly carboplatin, paclitaxel and cetuximab for 6 weeks with or without the addition of maintenance weekly cetuximab is defined as the time from Day 1 of treatment until progression or death as a result of any cause. (NCT02124707)
Timeframe: 36 months

InterventionDays (Median)
Carboplatin, Paclitaxel and Cetuximab132

[back to top]

Median Overall Survival

Overall survival after treatment with weekly carboplatin, paclitaxel and cetuximab for 6 weeks with or without the addition of maintenance weekly cetuximab is defined as the time from D1 of treatment under this protocol until death as a result of any cause. (NCT02124707)
Timeframe: 36 months

InterventionDays (Median)
Carboplatin, Paclitaxel and Cetuximab231

[back to top]

Pathological Complete Response (pCR) Rate

"-A patient is considered to not to have a pCR if any of the following are true:~There is histologic evidence of invasive tumor cells in the surgical breast specimen or the axillary lymph nodes.~The patient has discontinued neoadjuvant treatment early due to refusal, toxicity, or radiographic evidence of progression and then goes straight to surgery where there is histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes~The patient has discontinued neoadjuvant treatment early due to refusal, toxicity or radiographic evidence of progression and then receives alternative treatment.~The patient discontinues study treatment, refuses surgery, or is unable to undergo surgery due to a co-morbid condition.~Thus, any patient who does not receive alternative treatment prior to surgery and has no histologic evidence of invasive tumor cells in the surgical breast specimen and the axillary lymph nodes is considered to have a pCR." (NCT02124902)
Timeframe: At the time of surgery (surgery will take place 3-5 weeks after completion of treatment and estimated treatment length is 18 weeks)

InterventionParticipants (Count of Participants)
Washington University: Neoadjuvant Docetaxel and Carboplatin47
Baylor: Neoadjuvant Docetaxel and Carboplatin11

[back to top]

3-year Overall Survival

3-year overall survival (NCT02126969)
Timeframe: From date of randomization until date of death from any cause, assessed up to 3 years

InterventionParticipants (Count of Participants)
Chemotherapy Plus Radiation Therapy14
Chemotherapy Without Radiation11

[back to top]

Primary Site Complete Response Rate

Primary site is defined as the original, or first site that the cancer developed in the body. In this study, primary sites within the head and neck included squamous cancers of the larynx, oral cavity, oropharynx, hypopharynx.Complete response rate in patients treated with 2 cycles of induction Docetaxel and Carboplatin with low dose fractionated radiation therapy (LDFRT) will be compared to those treated with chemotherapy alone. CRR was determined Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or MRI: Complete Response (CR), Disappearance of all target lesions; Where possible, surgeon also evaluated primary site and provided response assessment. (NCT02126969)
Timeframe: Up to 50 days

InterventionParticipants (Count of Participants)
Chemotherapy Plus Radiation Therapy6
Chemotherapy Without Radiation4

[back to top]

Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy.

"Quality of Life (QOL) will be measured pre- and post-treatment using a single 5-question QOL well-being survey. The change in score will be presented independently for each subpart of the QOL survey.~Physical; scores range from 7-35; higher scores indicate increased well-being~Social/family; scores range from 7-35; higher scores indicate increased well-being~Emotional; scores range from 6-30; higher scores indicate increased well-being~Functional; scores range from 7-35; higher scores indicate increased well-being~Additional Concerns; scores range from 10-50; lower scores indicate increased well-being~FACT-G is the sum of the first 4 scores; scores range from 27-135; higher scores indicated increased well-being~FACT-H&N is the sum of the first five scores; scores range from 37-185; higher scores indicated increased well-being~Trial Outcome Index is the sum of 1, 4 and 5; scores range from 24-120; higher scores indicated increased well-being" (NCT02126969)
Timeframe: Up to 50 days (pre- and post-treatment)

,
Interventionchange in score (Mean)
PHYSICAL WELL-BEING SCORESOCIAL/FAMILY WELL-BEING SCOREEMOTIONAL WELL-BEING SCOREFUNCTIONAL WELL-BEING SCOREFACT-G TOTAL SCOREADDITIONAL CONCERNS SCOREFACT-H&N TOTAL SCORETRIAL OUTCOME INDEX SCORE
Chemotherapy Plus Radiation Therapy-1.46-1.342.05-0.48-1.235.013.793.08
Chemotherapy Without Radiation-1.64-2.341.60-1.70-4.083.63-0.460.29

[back to top]

Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales

Participants rated their function on EORTC QLQ C-30, with total score and single-item (physical, cognitive and role functioning) scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Clinically meaningful deterioration was defined as a decrease in score of 10 points in physical function; decrease of 7 points in cognitive function and decrease of 14 points in role function. (NCT02131064)
Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

,
InterventionPercentage of Participants (Number)
Cognitive FunctioningPhysical FunctioningRole Functioning
T-DM1 + P42.440.047.8
TCH + P59.172.576.7

[back to top]

Percentage of Participants by Response for Skin Problem Single Items

"Participants answered the Question 1 Did itching skin bother you? and Question 2 Have you had skin problems?, from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported." (NCT02131064)
Timeframe: Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months)

,
InterventionPercentage of Participants (Number)
Q1: Not at all: BaselineQ1: A little bit: BaselineQ1: Somewhat: BaselineQ1: Quite a bit: BaselineQ1: Very much: BaselineQ1: Not at all: Neoadjuvant Cycle 3Q1: A little bit: Neoadjuvant Cycle 3Q1: Somewhat: Neoadjuvant Cycle 3Q1: Quite a bit: Neoadjuvant Cycle 3Q1: Very much: Neoadjuvant Cycle 3Q1: Not at all: Neoadjuvant Cycle 5Q1: A little bit: Neoadjuvant Cycle 5Q1: Somewhat: Neoadjuvant Cycle 5Q1: Quite a bit: Neoadjuvant Cycle 5Q1: Very much: Neoadjuvant Cycle 5Q1: Not at all: Pre-SurgeryQ1: A little bit: Pre-SurgeryQ1: Somewhat: Pre-SurgeryQ1: Quite a bit: Pre-SurgeryQ1: Very much: Pre-SurgeryQ1: Not at all: Adjuvant Cycle 4Q1: A little bit: Adjuvant Cycle 4Q1: Somewhat: Adjuvant Cycle 4Q1: Quite a bit: Adjuvant Cycle 4Q1: Very much: Adjuvant Cycle 4Q1: Not at all: Adjuvant Cycle 8Q1: A little bit: Adjuvant Cycle 8Q1: Somewhat: Adjuvant Cycle 8Q1: Quite a bit: Adjuvant Cycle 8Q1: Very much: Adjuvant Cycle 8Q1: Not at all: End of TherapyQ1: A little bit: End of TherapyQ1: Somewhat: End of TherapyQ1: Quite a bit: End of TherapyQ1: Very much: End of TherapyQ1: Not at all: Follow-up 2Q1: A little bit: Follow-up 2Q1: Somewhat: Follow-up 2Q1: Quite a bit: Follow-up 2Q1: Very much: Follow-up 2Q1: Not at all: Follow-up 4Q1: A little bit: Follow-up 4Q1: Somewhat: Follow-up 4Q1: Quite a bit: Follow-up 4Q1: Very much: Follow-up 4Q2: Not at all: BaselineQ2: A little bit: BaselineQ2: Somewhat: BaselineQ2: Quite a bit: BaselineQ2: Very much: BaselineQ2: Not at all: Neoadjuvant Cycle 3Q2: A little bit: Neoadjuvant Cycle 3Q2: Somewhat: Neoadjuvant Cycle 3Q2: Quite a bit: Neoadjuvant Cycle 3Q2: Very much: Neoadjuvant Cycle 3Q2: Not at all: Neoadjuvant Cycle 5Q2: A little bit: Neoadjuvant Cycle 5Q2: Somewhat: Neoadjuvant Cycle 5Q2: Quite a bit: Neoadjuvant Cycle 5Q2: Very much: Neoadjuvant Cycle 5Q2: Not at all: Pre-SurgeryQ2: A little bit: Pre-SurgeryQ2: Somewhat: Pre-SurgeryQ2: Quite a bit: Pre-SurgeryQ2: Very much: Pre-SurgeryQ2: Not at all: Adjuvant Cycle 4Q2: A little bit: Adjuvant Cycle 4Q2: Somewhat: Adjuvant Cycle 4Q2: Quite a bit: Adjuvant Cycle 4Q2: Very much: Adjuvant Cycle 4Q2: Not at all: Adjuvant Cycle 8Q2: A little bit: Adjuvant Cycle 8Q2: Somewhat: Adjuvant Cycle 8Q2: Quite a bit: Adjuvant Cycle 8Q2: Very much: Adjuvant Cycle 8Q2: Not at all: End of TherapyQ2: A little bit: End of TherapyQ2: Somewhat: End of TherapyQ2: Quite a bit: End of TherapyQ2: Very much: End of TherapyQ2: Not at all: Follow-up 2Q2: A little bit: Follow-up 2Q2: Somewhat: Follow-up 2Q2: Quite a bit: Follow-up 2Q2: Very much: Follow-up 2Q2: Not at all: Follow-up 4Q2: A little bit: Follow-up 4Q2: Somewhat: Follow-up 4Q2: Quite a bit: Follow-up 4Q2: Very much: Follow-up 4
T-DM1 + P72.616.102.20.448.927.404.01.846.226.006.31.348.021.505.81.339.021.506.72.239.015.706.33.142.622.906.71.839.914.804.02.237.712.104.51.367.317.905.80.424.238.6014.84.525.637.7012.64.027.437.208.14.024.230.909.44.925.624.209.94.527.430.0013.53.127.825.606.31.330.018.804.52.2
TCH + P71.914.902.3035.331.2010.92.348.923.107.72.340.326.707.22.738.523.509.56.834.827.609.04.139.426.706.84.543.919.003.60.946.210.403.21.464.721.303.20.514.040.7018.66.821.335.7020.45.021.333.9015.46.323.533.0013.19.023.135.7012.25.027.133.9010.06.836.225.804.11.839.814.504.52.7

[back to top]

Percentage of Participants by Response for Neuropathy Single Item

"Participants answered the question Did you have tingling hands/feet?, from the Modified Quality of Life Questionnaire Breast Cancer 23 (mQLQ-BR23), on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported." (NCT02131064)
Timeframe: Baseline,Cycle(C) 3,C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4 (approx 47 months)

,
InterventionPercentage of Participants (Number)
Not at all: BaselineA little bit: BaselineSomewhat: BaselineQuite a bit: BaselineVery much: BaselineNot at all: Neoadjuvant Cycle 3A little bit: Neoadjuvant Cycle 3Somewhat: Neoadjuvant Cycle 3Quite a bit: Neoadjuvant Cycle 3Very much: Neoadjuvant Cycle 3Not at all: Neoadjuvant Cycle 5A little bit: Neoadjuvant Cycle 5Somewhat: Neoadjuvant Cycle 5Quite a bit: Neoadjuvant Cycle 5Very much: Neoadjuvant Cycle 5Not at all: Pre-SurgeryA little bit: Pre-SurgerySomewhat: Pre-SurgeryQuite a bit: Pre-SurgeryVery much: Pre-SurgeryNot at all: Adjuvant Cycle 4A little bit: Adjuvant Cycle 4Somewhat: Adjuvant Cycle 4Quite a bit: Adjuvant Cycle 4Very much: Adjuvant Cycle 4Not at all: Adjuvant Cycle 8A little bit: Adjuvant Cycle 8Somewhat: Adjuvant Cycle 8Quite a bit: Adjuvant Cycle 8Very much: Adjuvant Cycle 8Not at all: End of TherapyA little bit: End of TherapySomewhat: End of TherapyQuite a bit: End of TherapyVery much: End of TherapyNot at all: Follow-up 2A little bit: Follow-up 2Somewhat: Follow-up 2Quite a bit: Follow-up 2Very much: Follow-up 2Not at all: Follow-up 4A little bit: Follow-up 4Somewhat: Follow-up 4Quite a bit: Follow-up 4Very much: Follow-up 4
T-DM1 + P81.29.400.9059.619.302.70.454.321.102.71.852.017.905.41.342.615.209.02.731.819.309.04.031.423.8012.16.732.719.307.61.332.717.903.11.8
TCH + P78.79.500.90.554.320.803.21.837.129.908.66.822.629.0015.410.031.231.709.56.333.028.1010.94.131.230.8010.95.038.019.905.94.139.815.404.12.3

[back to top]

Percentage of Participants by Response for Hair Loss Single Item

"Participants answered the Question Have you lost any hair?, from the mQLQ-BR23, on a 5-point scale (1 'Not at all', 2 'A little', 3 'Somewhat', 4 'Quite a bit', 5 'Very much'). Percentage of participants by each response was reported." (NCT02131064)
Timeframe: Baseline,Cycle(C) 3, C5 of neoadjuvant period (each C=21 days); pre-surgery visit (within 6weeks after neoadjuvant therapy; up to approx 6months), C4 & 8 of Adjuvant Period (each C=21 days), End of Treatment, Follow up 2 & 4(approx 47 months)

,
InterventionPercentage of Participants (Number)
Not at all: BaselineA little bit: BaselineSomewhat: BaselineQuite a bit: BaselineVery much: BaselineNot at all: Neoadjuvant Cycle 3A little bit: Neoadjuvant Cycle 3Somewhat: Neoadjuvant Cycle 3Quite a bit: Neoadjuvant Cycle 3Very much: Neoadjuvant Cycle 3Not at all: Neoadjuvant Cycle 5A little bit: Neoadjuvant Cycle 5Somewhat: Neoadjuvant Cycle 5Quite a bit: Neoadjuvant Cycle 5Very much: Neoadjuvant Cycle 5Not at all: Pre-SurgeryA little bit: Pre-SurgerySomewhat: Pre-SurgeryQuite a bit: Pre-SurgeryVery much: Pre-SurgeryNot at all: Adjuvant Cycle 4A little bit: Adjuvant Cycle 4Somewhat: Adjuvant Cycle 4Quite a bit: Adjuvant Cycle 4Very much: Adjuvant Cycle 4Not at all: Adjuvant Cycle 8A little bit: Adjuvant Cycle 8Somewhat: Adjuvant Cycle 8Quite a bit: Adjuvant Cycle 8Very much: Adjuvant Cycle 8Not at all: End of TherapyA little bit: End of TherapySomewhat: End of TherapyQuite a bit: End of TherapyVery much: End of TherapyNot at all: Follow-up 2A little bit: Follow-up 2Somewhat: Follow-up 2Quite a bit: Follow-up 2Very much: Follow-up 2Not at all: Follow-up 4A little bit: Follow-up 4Somewhat: Follow-up 4Quite a bit: Follow-up 4Very much: Follow-up 4
T-DM1 + P87.44.000065.016.600.4058.719.301.30.449.824.702.2050.215.702.21.348.914.300.9057.814.8001.348.411.700.40.441.311.202.70.4
TCH + P81.47.700.508.611.3020.839.420.419.9015.826.230.813.6011.321.367.95.003.22.770.14.100.90.969.75.400.91.855.79.001.41.852.97.2001.4

[back to top]

Minimum Observed Serum Concentration (Cmin) of Trastuzumab

Only participants who received trastuzumab were to be analyzed for this outcome. (NCT02131064)
Timeframe: Pre-study treatment infusion (0 hours [hr]) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period

Interventionmcg/mL (Mean)
Trastuzumab (neoadjuvant period)Trastuzumab (adjuvant period)
TCH + P45.821.8

[back to top]

Maximum Observed Serum Concentration (Cmax) of Trastuzumab

Only participants who received trastuzumab were to be analyzed for this outcome. (NCT02131064)
Timeframe: 15-30 minutes (min) post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period

Interventionmicrograms per milliliter (mcg/mL) (Mean)
Cycle 1 (neoadjuvant period)Cycle 6 (neoadjuvant period)Cycle 1 (adjuvant period)Cycle 6 (adjuvant period)
TCH + P167148159181

[back to top]

Cmin of Trastuzumab Emtansine and Total Trastuzumab

Only participants who received trastuzumab emtansine were to be analyzed for this outcome. (NCT02131064)
Timeframe: Pre-study treatment infusion (0 hr) (infusion duration = 90 min) on Day 1 of Cycle 6 (cycle length = 21 days) in neoadjuvant and adjuvant period

Interventionmcg/mL (Mean)
Trastuzumab emtansine (neoadjuvant)Total Trastuzumab (neoadjuvant)Trastuzumab emtansine (adjuvant)Total Trastuzumab (adjuvant)
T-DM1 + P3.0412.34.098.70

[back to top]

Cmax of Trastuzumab Emtansine and Total Trastuzumab

Only participants who received trastuzumab emtansine were to be analyzed for this outcome. (NCT02131064)
Timeframe: 15-30 min post-study treatment infusion (infusion duration = 90 min) on Day 1 of Cycle 1 and 6 (each cycle = 21 days) in neoadjuvant and adjuvant period.

Interventionmcg/mL (Mean)
Trastuzumab emtansine: C1 (neoadjuvant)Trastuzumab emtansine: C6 (neoadjuvant)Total Trastuzumab: C1 (neoadjuvant)Total Trastuzumab: C6 (neoadjuvant)Trastuzumab emtansine: C1 (adjuvant)Trastuzumab emtansine: C6 (adjuvant)Total Trastuzumab: C1 (adjuvant)Total Trastuzumab: C6 (adjuvant)
T-DM1 + P80.471.779.179.170.473.173.082.6

[back to top]

Time to Clinically Meaningful Deterioration in GHS/QoL Score

Participants rated their quality of life (global health status) on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by GHS/QoL. All valid GHS/QoL questionnaires of the neoadjuvant phase including surgery were used. Participants without deterioration were censored at the time of completing the last GHS/QoL plus 1 day. Median time to deterioration was estimated with Kaplan-Meier method. The 95% confidence interval (CI) for the median was computed using the method of Brookmeyer and Crowley. (NCT02131064)
Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

Interventionmonths (Median)
TCH + P3.02
T-DM1 + P4.63

[back to top]

Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples

tpCR was assessed by local pathology review on samples taken at surgery following completion of neoadjuvant therapy. tpCR was defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes ( that is [i.e.], ypT0/is, ypN0 in the American Joint Committee on Cancer [AJCC] staging system, 7th edition). Percentage of participants with tpCR was reported. (NCT02131064)
Timeframe: Pre-surgery (within 6 weeks after neoadjuvant therapy; up to approximately 6 months)

InterventionPercentage of Participants (Number)
TCH + P56.1
T-DM1 + P44.4

[back to top]

Percentage of Participants With a Clinically Meaningful Deterioration in Global Health Status (GHS)/Quality of Life (QoL) Score

Participants rated their quality of life (global health status) on European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ- C30), with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better quality of life. Clinically meaningful deterioration in GHS/QoL was defined as a decrease in score of 10 points in GHS/QoL. (NCT02131064)
Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

InterventionPercentage of Participants (Number)
TCH + P69.9
T-DM1 + P45.4

[back to top]

Percentage of Participants Who Received Breast-Conserving Surgery (BCS)

BCS rate was defined as the percentage of participants who achieve BCS out of the ITT population of participants without inflammatory breast cancer. (NCT02131064)
Timeframe: Surgery performed after completion of neoadjuvant therapy (approximately 6 months after neoadjuvant period)

InterventionPercentage of Participants (Number)
TCH + P52.6
T-DM1 + P41.7

[back to top]

Overall Survival

Overall survival in the overall study population was defined as the time from the date of randomization to the date of death from any cause. 3 years OS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. (NCT02131064)
Timeframe: From randomization until death (up to approximately 47 months)

InterventionProbability (Number)
TCH + P97.6
T-DM1 + P97.0

[back to top]

Invasive Disease-free Survival (IDFS)

IDFS is defined only for participants who undergo surgery. IDFS is defined as the time from surgery to the first documented occurrence of an IDFS event, defined as: Ipsilateral invasive breast tumor recurrence; Ipsilateral local-regional invasive breast cancer recurrence; Distant recurrence; Contralateral invasive breast cancer; and death from any cause. 3 years of IDFS event-free rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. (NCT02131064)
Timeframe: From surgery to the first documented occurrence of IDFC event (up to approximately 47 months)

InterventionProbability (Number)
TCH + P91.99
T-DM1 + P93.04

[back to top]

Event-Free Survival

Event-free survival (EFS) is defined as the time from randomization to disease progression or disease recurrence (local, regional, distant, or contralateral, invasive or non-invasive), or death from any cause. 3 years EFS rate per randomized treatment arms in the ITT population were estimated using the Kaplan-Meier method and estimated the probability of a patient being event-free after 3 years after treatment. (NCT02131064)
Timeframe: From randomization up to disease progression or recurrence or death (up to approximately 47 months)

InterventionProbability (Number)
TCH + P94.21
T-DM1 + P85.28

[back to top]

Time to Clinically Meaningful Deterioration in Function Subscale

Participants rated their function on EORTC QLQ C-30, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates better functioning. Time to deterioration was defined as the time from baseline to first 10-point (or greater) decrease as measured by physical function; to first 14-point (or greater) decrease as measured by role function, to first 7-point (or greater) decrease as measured by cognitive function. Median time to deterioration was estimated with Kaplan-Meier method. The 95% CI for the median was computed using the method of Brookmeyer and Crowley. (NCT02131064)
Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

,
Interventionmonths (Median)
Physical FunctionRole FunctionCognitive Function
T-DM1 + P4.864.444.44
TCH + P2.792.793.42

[back to top]

Serum Levels of Plasma DM1-Containing Catabolites Concentrations (in ng/mL) (Nonreducible Thioether Linker [MCC]-DM1 and Lysine [Lys]-MCC-DM1)

(NCT02131064)
Timeframe: 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period

Interventionng/mL (Mean)
C1: MCC-DM1 (Neoadjuvant Period)C1: Lys-MCC-DM1 (Neoadjuvant period)C6: MCC-DM1 (Neoadjuvant Period)C6: Lys-MCC-DM1 (Neoadjuvant period)C1: MCC-DM1 (Adjuvant Period)C1: Lys-MCC-DM1 (Adjuvant period)C6: MCC-DM1 (Adjuvant Period)C6: Lys-MCC-DM1 (Adjuvant period)
T-DM1 + P8.18NA8.22NA7.98NA7.90NA

[back to top]

Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) Concentrations

DM1 is the metabolite of trastuzumab emtansine. Only participants who received trastuzumab emtansine were to be analyzed for this outcome. (NCT02131064)
Timeframe: 15-30 min post-study treatment infusion (Cmax) on Day 1 of Cycle 1 and 6 in neoadjuvant and adjuvant period

Interventionnanograms per milliliter (ng/mL) (Mean)
C1: 15-30 min post-dose (neoadjuvant)C6: 15-30 min post-dose (neoadjuvant)C1: 15-30 min post-dose (adjuvant)C6: 15-30 min post-dose (adjuvant)
T-DM1 + P4.644.734.495.15

[back to top]

Percentage of Participants With Selected Adverse Events (AEs)

Selected AEs included hepatotoxicity, pulmonary toxicity, cardiac dysfunction, neutropenia, thrombocytopenia, peripheral neuropathy, hemorrhage, infusion related reaction (IRR)/hypersensitivity, IRR/Hypersensitivity symptoms, rash, diarrhea and mucositis. An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. (NCT02131064)
Timeframe: Baseline to end of study (approximately 47 months)

,
InterventionPercentage of Participants (Number)
HepatotoxicityPulmonary ToxicityCardiac DysfunctionNeutropeniaThrombocytopeniaPeripheral NeuropathyHemorrhageIRR/HypersensitivityIRR/Hypersensitivity symptomsRashDiarrheaMucositis
T-DM1 + P39.04.91.38.117.928.733.222.919.336.838.624.7
TCH + P14.20.94.639.722.847.519.213.77.844.776.743.8

[back to top]

Percentage of Participants With ATA to Trastuzumab

(NCT02131064)
Timeframe: Baseline (Pre-trastuzumab [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (Pre-trastuzumab infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period

InterventionPercentage of participants (Number)
Neoadjuvant Phase (baseline)Neoadjuvant Phase (post-baseline)Adjuvant Phase (baseline)Adjuvant Phase (post-baseline)
T-DM1 + P112.65.45.0

[back to top]

Percentage of Participants With Anti-Therapeutic Antibodies (ATA) to TDM-1

Participants were considered post-baseline ATA positive if they had ATAs post-baseline that were either treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a negative or missing ATA result at baseline, and at least one positive ATA result post-baseline. Participants had treatment-enhanced ATAs if they had a positive ATA result at baseline, and at least one positive ATA result post-baseline that was greater than or equal to (>/=) 0.60 titer units higher than the result at baseline. (NCT02131064)
Timeframe: Baseline (b) (Pre-TDM1 [0 hr] infusion [infusion duration = 90 min] on Day 1 of Cycle 1); post-baseline (pb) (Pre-TDM1 infusion [0 hr] on Day 1 of Cycle 6) (each cycle = 21 days) in neoadjuvant and adjuvant period

InterventionPercentage of Participants (Number)
Neoadjuvant Phase (Baseline)Neoadjuvant Phase (Post-Baseline)Adjuvant Phase (Baseline)Adjuvant Phase (Post-baseline)
T-DM1 + P5.57.511.713.1

[back to top]

Percentage of Participants With a Clinically Meaningful Increase in Symptom Subscales

Participants rated their symptoms on EORTC QLQ C-30 and mQLQ-BR23, with total scores ranging from 0 (worst) to 100 (best); where higher score indicates greater degree of symptoms. Clinically meaningful increase in symptoms was defined as an increase in score (deterioration) of 11 points in nausea and vomiting, pain, dyspnea; increase of 9 points in insomnia; increase of 14 points in appetite loss; increase of 15 points in diarrhea, constipation; increase of 10 points in fatigue, systemic therapy side effects, hair loss. (NCT02131064)
Timeframe: From Baseline (Day 1 Cycle 1) to Cycle 6 (each cycle = 21 days) in neoadjuvant period

,
InterventionPercentage of Participants (Number)
Appetite LossAny Hair LossSystemic Therapy Side-EffectsConstipationDiarrheaDyspneaFatigueNausea/VomitingPainInsomnia
T-DM1 + P47.840.575.132.750.731.268.843.936.630.2
TCH + P61.191.289.733.279.356.087.666.356.042.5

[back to top]

Progression Free Survival (PFS) Rate at Month 6

PFS was defined as the time from randomization to documented disease progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or death due to any cause, whichever occurred first and was based on blinded independent central radiologists' (BICR) review. Progressive Disease (PD) was defined as ≥20% increase in the sum of diameters of target lesions and an absolute increase of ≥5 mm. (Note: the appearance of one or more new lesions was also considered progression). Participants were evaluated every 9 weeks with radiographic imaging to assess their response to treatment. The data cutoff was 09-May-2016. The PFS rate at Month 6 was calculated. (NCT02142738)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Pembrolizumab62.1
SOC Chemotherapy50.3

[back to top]

Overall Survival (OS) Rate

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The data cutoff was 10-July-2017. The median OS rate at 12 months is presented. (NCT02142738)
Timeframe: 12 months

InterventionPercentage of Participants (Number)
Pembrolizumab70.3
SOC Chemotherapy54.8

[back to top]

Objective Response Rate (ORR)

ORR was defined as the percentage of participants in the analysis population who experienced a Complete Response (CR; disappearance of all target lesions) or a Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using RECIST 1.1 based on BICR evaluation. ORR was assessed from enrollment/treatment initiation of a participant through data cutoff of 09-May-2016. The ORR is presented for each treatment group. (NCT02142738)
Timeframe: Up to ~1.6 years

InterventionPercentage of Participants (Number)
Pembrolizumab44.8
SOC Chemotherapy27.8

[back to top]

Percentage of Participants With at Least 1 Treatment Emergent Adverse Event With Action Taken as Study Drug Withdrawn

The percentage of participants with at least 1 TEAE with action taken as studydrug withdrawn during the treatment period of the trial was assessed throughout the conduct of the study. Study drug withdrawn (treatment permanently discontinued) was attributed to the part in which the onset of the adverse event took place. (NCT02151149)
Timeframe: From the date of the first dose of IP until 28 days after the last dose of IP; up to a later data cut-off date of 14 July 2017 the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively

InterventionPercentage of Participants (Number)
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)25.0
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)20.0

[back to top]

Number of Participants With Treatment Emergent Adverse Events During the Treatment Period

"Treatment-emergent adverse events (TEAEs) were defined as any AE or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the IP through 28 days after the last dose of IP. Any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs was graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and based on the scale:~Grade 1 = Mild - transient or mild discomfort; Grade 2 = Moderate - mild to moderate limitation in activity, assistance may be needed; minimal medical intervention required; Grade 3 = Severe - marked limitation in activity, assistance usually required; medical intervention required, hospitalization is possible; Grade 4 = Life threatening - extreme limitation in activity, assistance required; medical intervention, hospitalization or hospice care probable; Grade 5 = death." (NCT02151149)
Timeframe: From the date of the first dose of IP until 28 days after the last dose of IP; up to a later data cut-off date of 14 July 2017; maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively.

,
InterventionParticipants (Count of Participants)
Treatment Emergent Adverse EventSerious Treatment Emergent Adverse EventGrade 3 or 4 Treatment Emergent Adverse EventGrade 3 or Higher Treatment Emergent Adverse EventTreatment Related TEAETreatment-Related Serious TEAETEAE with Action to Reduce or Interrupt IP DoseTreatment-Related Action to Reduce/Interrupt IPTEAE with Action Taken as Study Drug WithdrawnTreatment-related TEAE with Action to Halt IPTEAE with Fatal OutcomeTreatment-related TEAE with Fatal Outcome
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)6823606065126056171310
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)6932596166125451141330

[back to top]

Percentage of Participants With Either Peripheral Neuropathy ≥ Grade 2 or Myelosuppression Adverse Events (AEs) ≥ Grade 3 Based on Local Laboratory Values

Peripheral neuropathy (sensory or motor) assessment was done at screening, on Days 1, 8, 15 of every treatment cycle, at the End-of-Treatment visit and at the 28-day Follow-up Visit. Changes in neuropathy grade from baseline was reported as an AE as assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Myelosuppression in participants receiving chemotherapy may have manifested as neutropenia, thrombocytopenia, or anemia. Grade 3 neutropenia including an absolute neutropenia count (ANC) of 500 to 1,000 cells/mm^3; anemia hemoglobain levels (Hgb) <8.0 - 6.5 g/dL; <4.9 - 4.0 mmol/L; <80 - 65 g/L; transfusion indicated; and thrombocytopenia with platelet levels <100,000 cells/mm^3. (NCT02151149)
Timeframe: From the date of the first dose of investigational product (IP) until 28 days after the last dose of IP; up to data cut-off date of 20 November 2016; The median treatment duration for Arms A and B were 3.04 months and 5.17 months respectively.

InterventionPercentage of Participants (Number)
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)76.5
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)77.1

[back to top]

Percentage of Participants With a Dose Delay During the Entire Study

A dose delay occurred when the dose assigned at a visit was held compared to the previous visit. Dose delays were typically caused by clinically significant laboratory abnormalities and/or TEAEs or toxicities. (NCT02151149)
Timeframe: From the first dose of study treatment to discontinuation date of study treatment; up to date cut off date of 16 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively

,
InterventionPercentage of Participants (Number)
nab-PaclitaxelCarboplatin
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)58.852.9
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)48.644.3

[back to top]

Dose Intensity Per Week of Carboplatin During the Entire Study

"Dose intensity for carboplatin was the cumulative dose divided by the dosing period in weeks." (NCT02151149)
Timeframe: From day 1 of study treatment to the end date of study treatment; up to data cut off date of 20 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively

Interventionmg*min/mL/week (Mean)
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)1.51
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)1.33

[back to top]

Percentage of Participants With Dose Reductions During the Entire Study

A dose reduction occurred when the dose assigned at a visit was lower than the dose assigned at the previous visit. Dose reductions were typically caused by clinically significant laboratory abnormalities and/or TEAEs or toxicities. (NCT02151149)
Timeframe: From the first dose of study treatment to discontinuation date of study treatment; up to date cut off date of 20 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively

,
InterventionPercentage of Participants (Number)
nab-PaclitaxelCarboplatin
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)64.757.4
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)58.658.6

[back to top]

Dose Intensity Per Week of Nab-Paclitaxel During the Entire Study

Dose intensity was the cumulative dose divided by the dosing period in weeks. (NCT02151149)
Timeframe: From day 1 of study treatment to the end date of study treatment; up to data cut off date of 20 November 2016; the maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively

Interventionmg/m^2/week (Mean)
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)64.07
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)56.57

[back to top]

Kaplan Meier Estimate of Overall Survival (OS)

Overall survival was defined as the time in months between day 1 of treatment and death from any cause). Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off, whichever was earlier. Participants who were lost to follow-up prior to the end of the study or who were withdrawn from the study were censored at the time of last contact. (NCT02151149)
Timeframe: From first dose of IP to the date of death due to any cause; up to a later clinical cut-off date of 14 July 2017; for Arms A and B participants were followed for OS for 31 months and 33 months respectively

Interventionmonths (Median)
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)14.52
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)14.98

[back to top]

Kaplan Meier Estimate of Progression-Free Survival (PFS)

Progression-free survival was defined as the time in months from day 1 of treatment to the date of disease progression based on the investigator's assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred earlier. RECIST V1.1 criteria includes: - Complete Response (CR) is the disappearance of all target lesions; - Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions from baseline; - Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease (PD); - Progressive Disease is at least a 20% increase in the sum of diameters of target lesions from nadir (NCT02151149)
Timeframe: From first dose of IP to the date of disease progression; up to a later clinical cut-off date of 14 July 2017; for Arms A and B participants were followed for PFS for 31 months and 20 months respectively

Interventionmonths (Median)
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)3.88
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)7.20

[back to top]

Percentage of Participants Who Achieved a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to RECIST 1.1 Criteria

Overall response rate (ORR) was defined as the percentage of participants who had radiologic CR or PR compared to baseline (radiographic evaluation on the day of or within 28 days prior to randomization) according to RECIST Version 1.1 criteria as determined by the investigator, which was confirmed by repeated radiologic assessment performed no less than 28 days after the criteria for response were first met and occurred between Day 1 of treatment and the start of subsequent anticancer therapy, death or study discontinuation. A complete response and partial response per RECIST V 1.0 criteria was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of diameters of target lesions from baseline. (NCT02151149)
Timeframe: From the first dose of IP to the date of documented first response; up to the data cut-off date of 14 July 2017; maximum treatment duration for Arms A and B was 16.6 months and 20.1 months respectively.

InterventionPercentage of participants (Number)
Arm A: Nab-Paclitaxel and Carboplatin (21-day Treatment Cylce)26.8
Arm B: Nab-Paclitaxel and Carboplatin (28-day Treatment Cycle)41.7

[back to top]

Progression-Free Survival (PFS)

Time to PFS is defined as the number of days from the date the participant was randomized to the date the participant experiences radiographic disease progression (as determined by the investigators), or to the date of death (all causes of mortality) if disease progression is not reached. All events of disease progression occurring on or before the Primary Analysis Cutoff date of 05 April 2019 were to be included, regardless of whether the event occurred while the participant was still taking study drug or had previously discontinued study drug. PFS was estimated for each treatment group using Kaplan-Meier methodology. (NCT02163694)
Timeframe: From randomization until the primary analysis data cut-off date of 05 April 2019; the median duration of follow-up was 35.5 months

Interventionmonths (Median)
Veliparib Placebo With Carboplatin and Paclitaxel12.6
Veliparib With Carboplatin and Paclitaxel14.5

[back to top] [back to top]

Percentage of Participants With Local-regional Progression

Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: [1] ≥ 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of ≥1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported. (NCT02186847)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.

Interventionpercentage of participants (Number)
Chemoradiation17.2
Metformin + Chemoradiation20.5

[back to top]

Percentage of Participants With Distant Metastases

Distant metastasis (DM) is defined as the appearance of ≥ 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported. (NCT02186847)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.

Interventionpercentage of participants (Number)
Chemoradiation17.2
Metformin + Chemoradiation20.5

[back to top]

Percentage of Participants Alive Without Progression (Progression-free Survival)

Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: [1] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported. (NCT02186847)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.

Interventionpercentage of participants (Number)
Chemoradiation60.4
Metformin + Chemoradiation51.3

[back to top]

Percentage of Participants Alive (Overall Survival)

Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported. (NCT02186847)
Timeframe: From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.

Interventionpercentage of participants (Number)
Chemoradiation38.5
Metformin + Chemoradiation40.1

[back to top]

Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.

ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment. (NCT02187744)
Timeframe: Cycle 6/End of treatment

InterventionPercentage of participants (Number)
PF-0528001488.1
Trastuzumab-EU82.0

[back to top]

Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.

Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response. (NCT02187744)
Timeframe: Cycle 6/End of treatment

InterventionPercentage of participants (Number)
PF-0528001447.0
Trastuzumab-EU50.0

[back to top]

Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.

The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) >20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group. (NCT02187744)
Timeframe: Cycle 5

InterventionPercentage of participants (Number)
PF-0528001492.1
Trastuzumab-EU93.3

[back to top]

Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.

The number of participants with positive (titer >=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive. (NCT02187744)
Timeframe: Cycles 1 through 6

,
InterventionNumber of participants (Number)
Cycle 1 (n=113,112)Cycle 2 (n=111,112)Cycle 4 (n=108,109)Cycle 6 (n=108,108)
PF-052800140000
Trastuzumab-EU1000

[back to top]

Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.

Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation. (NCT02187744)
Timeframe: Cycles 1 through 6

,
Interventionμg/mL (Mean)
Cycle 1/Day 1 0 hours N= 101, 88Cycle 1/Day 1 1 hour N= 97, 80Cycle 2/Day 21 0 hours N= 99, 88Cycle 4/Day 63 0 hours N= 98, 89Cycle 5/Day 84 0 hours N= 101, 87Cycle 5/Day 84 1 hour N= 90, 80Cycle 6/Day 105 0 hours N= 101, 89
PF-052800142.313160.424.2933.4335.01137.037.77
Trastuzumab-EU1.318164.827.2037.3340.44138.840.10

[back to top]

Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.

The number of participants with positive (NAb response >=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive. (NCT02187744)
Timeframe: Cycles 1 through 6

,
InterventionNumber of participants (Number)
Cycle 1 (n=113,112)Cycle 2 (n=110,112)Cycle 4 (n=108,110)Cycle 6 (n=108,108)
PF-052800140000
Trastuzumab-EU0000

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionMonths (Median)
Pembrolizumab5.4
Chemotherapy (SOC Treatment)6.6

[back to top]

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%

OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionMonths (Median)
Pembrolizumab18.0
Chemotherapy (SOC Treatment)13.0

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionPercentage of participants (Number)
Pembrolizumab27.2
Chemotherapy (SOC Treatment)26.5

[back to top]

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%

OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionMonths (Median)
Pembrolizumab20.0
Chemotherapy (SOC Treatment)12.2

[back to top]

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%

OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionMonths (Median)
Pembrolizumab16.4
Chemotherapy (SOC Treatment)12.1

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionPercentage of participants (Number)
Pembrolizumab39.1
Chemotherapy (SOC Treatment)32.0

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionPercentage of participants (Number)
Pembrolizumab33.2
Chemotherapy (SOC Treatment)28.9

[back to top]

Number of Participants Who Experienced At Least One Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. (NCT02220894)
Timeframe: Up to approximately 38 months

InterventionParticipants (Count of Participants)
Pembrolizumab608
Chemotherapy (SOC Treatment)606

[back to top]

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. (NCT02220894)
Timeframe: Up to approximately 35 months

InterventionParticipants (Count of Participants)
Pembrolizumab126
Chemotherapy (SOC Treatment)93

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionMonths (Median)
Pembrolizumab6.5
Chemotherapy (SOC Treatment)6.4

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented. (NCT02220894)
Timeframe: Up to approximately 44 months

InterventionMonths (Median)
Pembrolizumab6.2
Chemotherapy (SOC Treatment)6.7

[back to top]

Maximum Tolerated Dose of Brentuximab Vedotin That Can be Combined With Ifosfamide, Carboplatin, and Etoposide Chemotherapy

Will be defined as the dose at which =< 1 of 6 patients experience a dose-limiting toxicity. Dose-limiting toxicity will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. (NCT02227199)
Timeframe: Up to 28 days following the second course of chemotherapy, approximately 70 days

Interventionmg/kg (Number)
Treatment (Brentuximab, Ifosfamide, Carboplatin, Etoposide)1.5

[back to top]

2 Year Progression-free Survival

(NCT02227199)
Timeframe: Up to 2 years from initiation of therapy.

InterventionParticipants (Count of Participants)
Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)2
Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)3
Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)33

[back to top]

Percentage of Patients That Achieve a Complete Remission Following Study Treatment

(NCT02227199)
Timeframe: 3 weeks following the completion of chemotherapy

InterventionParticipants (Count of Participants)
Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)3
Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)3
Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)26

[back to top]

2 Year Overall Survival

(NCT02227199)
Timeframe: Up to 2 years from initiation of study therapy.

InterventionParticipants (Count of Participants)
Phase I: Dose Escalation, Dose Level 1 (Brentuximab 1.2mg/kg, Ifosfamide, Carboplatin, Etoposide)3
Phase I: Dose Escalation, Dose Level 2 (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)3
Phase II: Dose Expansion (Brentuximab 1.5mg/kg, Ifosfamide, Carboplatin, Etoposide)37

[back to top]

Rates of Acute Toxicity, Determined by Incidence of Mucositis, Xerostomia, Anorexia, Weight Loss, Dermatitis and G-tube Placement

Toxicity rates will be summarized by type of toxicity, grade, and attribution. The incidence of acute (mucositis, xerostomia, anorexia, weight loss, dermatitis and G-tube placement) toxicities will be estimated along with 95% confidence intervals. Toxicity criteria of the Common Toxicity Criteria (CTC) and the Radiation Therapy Oncology Group (RTOG) will be used to determine grades. General CTC grade definitions: 0 = No adverse event or within normal limits; 1 = Mild adverse event; 2 = Moderate adverse event; 3 = Severe and undesirable adverse event; 4 = Life-threatening or disabling adverse event; 5 = Death related to adverse event. For Mucous, 3 = Confluent fibrinous, mucositis / may include severe pain requiring narcotic; 4 = Ulceration, hemorrhage or necrosis. For neutropenia, 3 = Neutrophils 0.5 - < 1.0; 4 = Neutrophils < 0.5 or sepsis. (NCT02258659)
Timeframe: Up to 5 years

Interventionparticipants (Number)
Grade 3+ mucositisGrade 3+ dermatitisgrade 3+ neutropeniagrade 3+ Anorexia
Single Arm3512295

[back to top]

Rates of Late Toxicity, Determined by Incidence of Xerostomia, Dental Decay, Osteroradionecrosis, G-tube Dependency, Tracheostomy Placement and Dysphagia

Toxicity rates will be summarized by type of toxicity, grade, and attribution. The incidence of late-term (xerostomia, dental decay, osteroradionecrosis, G-tube dependency, speech abnormalities, tracheostomy placement and dysphagia) toxicities will be estimated along with 95% confidence intervals. (NCT02258659)
Timeframe: Up to 5 years

Interventionparticipants (Number)
G-tube dependenceDysphagia
Single Arm1818

[back to top]

Cancer-specific Survival

Overall Cancer-specific survival rate. Patients dying from non-cancer related causes will be censored at the time of death. (NCT02258659)
Timeframe: Up to 5 years

Interventionpercentage of participants (Number)
Single Arm95

[back to top]

Overall Survival

Overall survival rate (NCT02258659)
Timeframe: From the date of registration to the date of death or date of last patient contact if censored, assessed up to 5 years

Interventionpercentage of participants (Number)
Single Arm87

[back to top]

Progression-Free Survival (PFS), Evaluated Using RECIST Version (v) 1.1

If all patients are followed for two years, the PFS rate and confidence interval will be determined based on the exact binomial distribution. Otherwise, PFS will be estimated using the Kaplan-Meier method and a (large-sample) one-sided 90% confidence interval will be derived for the PFS rate at two years to test the non-inferiority hypothesis. Median PFS will be estimated as described in Brookmeyer and Crowley. (NCT02258659)
Timeframe: Time from enrollment until disease progression or death from any cause, assessed at 2 years

Interventionpercentage of participants (Number)
Single Arm94.5

[back to top]

Rate of Pathologic Complete Response (PCR) on Post Treatment Biopsy/Surgery, Evaluated Using RECIST v1.1

Pathologic response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution. (NCT02258659)
Timeframe: Up to 8 weeks after completion of CRT

Interventionpercentage of participants (Number)
Single Arm90

[back to top]

Clinical Complete Response by Computerized Tomography (CT) & Magnetic Resonance Imaging (MRI) Only

Clinical response rates will be determined and 95% confidence intervals obtained using the exact binomial distribution. (NCT02258659)
Timeframe: Up to 5 years

Interventionpercentage of participants (Number)
complete responsePartial ResponseStable Disease
Single Arm138013

[back to top]

Overall Survival in All Participants

Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. OS was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive. (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy12.1
Veliparib + Carboplatin + Paclitaxel12.1

[back to top]

Progression Free Survival (PFS) in All Participants

"Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per RECIST version 1.1 or death (all causes of mortality), whichever occurred first.~PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.~PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cut-off date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death." (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy6.7
Veliparib + Carboplatin + Paclitaxel5.9

[back to top]

Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup

"Progression-free survival is defined as the time from the date of randomization to the date of disease progression (PD) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 or death (all causes of mortality), whichever occurred first.~PD: At least a 20% increase in the size of target lesions, taking as reference the smallest size recorded since the treatment started (Baseline or after) with an absolute increase of at least 5 mm, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions.~PFS was estimated using Kaplan-Meier methodology. Participants who did not have an event of disease progression or had not died on or before the cutoff date were censored at the date of their last disease progression assessment on or before the cut-off date. Any PD and death occurring > 26 weeks and > 12 weeks after the previous assessment, respectively, were excluded and patients were censored at last assessment before PD or death." (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy5.2
Veliparib + Carboplatin + Paclitaxel6.3

[back to top]

Objective Response Rate (ORR) in All Participants

"Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per RECIST version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.~CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions." (NCT02264990)
Timeframe: Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively.

Interventionpercentage of participants (Number)
Investigator's Choice Chemotherapy29.0
Veliparib + Carboplatin + Paclitaxel26.2

[back to top]

Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup

"Objective response rate is defined as the percentage of participants with a complete response (CR) or partial response (PR) per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 criteria. Response must have been confirmed at a consecutive assessment 28 days or more after the assessment at which response was first observed.~CR: The disappearance of all target and non-target lesions and no new lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum diameters, persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits, or any new lesions." (NCT02264990)
Timeframe: Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively.

Interventionpercentage of participants (Number)
Investigator's Choice Chemotherapy30.0
Veliparib + Carboplatin + Paclitaxel22.5

[back to top]

Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup

Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive. (NCT02264990)
Timeframe: From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.

Interventionmonths (Median)
Investigator's Choice Chemotherapy9.2
Veliparib + Carboplatin + Paclitaxel11.2

[back to top] [back to top] [back to top]

Multiple Dose Adavosertib Cmax

Maximum plasma concentration of adavosertib after a multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin. (NCT02272790)
Timeframe: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

InterventionnM (Geometric Mean)
Arm D 175 mg4135
Arm D 225 mg23530

[back to top]

Progression Free Survival (Median, 80% CI)

"Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.~Progression-free survival was derived based on scan/assessment dates, not visit dates." (NCT02272790)
Timeframe: Throughout the Study, Approximately 4 years

InterventionMonths (Median)
Arm A1.7
Arm B5.5
Arm C4.2
Arm C212.0
Arm D-175 mg2.7
Arm D-225 mgNA

[back to top]

Serious Adverse Events

The number of patients experiencing at least one serious adverse event (SAE). (NCT02272790)
Timeframe: Throughout the duration of the study (up to 19 months)

,,,,,
InterventionParticipants (Number)
Pts. with ≥ one serious TEAE related to AZD1775.Pts. with ≥ one serious TEAE related to Chemo.
Arm A00
Arm B88
Arm C99
Arm C277
Arm D-175 mg11
Arm D-225 mg11

[back to top] [back to top]

Serious Adverse Events Leading to Death

The number of patients experiencing at least one serious adverse event (SAE) leading to death. (NCT02272790)
Timeframe: Throughout the duration of the study (up to 19 months)

,,,,,
InterventionParticipants (Number)
No. with STEAE related to AZD1775 leading to deathNo. with STEAE related to chemo leading to death
Arm A00
Arm B11
Arm C00
Arm C200
Arm D-175 mg00
Arm D-225 mg00

[back to top] [back to top] [back to top] [back to top] [back to top]

Overall Survival (Median, 95% CI)

Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive. (NCT02272790)
Timeframe: Throughout the Study, Approximately 4 years

InterventionMonths (Median)
Arm A16.0
Arm BNA
Arm C8.9
Arm C219.2
Arm D-175 mg6.2
Arm D-225 mgNA

[back to top]

Single Dose Adavosertib Cmax

Maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin. (NCT02272790)
Timeframe: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

InterventionnM (Geometric Mean)
Arm A 800 mg/m² Gemcitabine477.4
Arm A 1000 mg/m² Gemcitabine571.1
Arm B533.8
Arm C556.6

[back to top]

Overall Survival (Median, 80% CI)

Overall survival (OS) was defined as the elapsed time from the date of first dose of AZD1775 until death due to any cause. Any patient not known to have died at the time of the analysis was censored based on the last recorded date on which the patient was known to be alive. (NCT02272790)
Timeframe: Throughout the Study, Approximately 4 years

InterventionMonths (Median)
Arm A16.0
Arm BNA
Arm C8.9
Arm C219.2
Arm D-175 mg3.8
Arm D-225 mgNA

[back to top]

Objective Response Rate (ORR)

Objective response rate is defined as the proportion of patients achieving a complete or partial tumour response according to RECIST v1.1 criteria. (NCT02272790)
Timeframe: Throughout the duration of the study (up to 19 months)

InterventionParticipants (Number)
Arm A1
Arm B11
Arm C7
Arm C28
Arm D-175 mg2
Arm D-225 mg1

[back to top]

Single Dose Adavosertib Tmax

The time to reach maximum plasma concentration of adavosertib after a single oral dose (Cycle 1 Day 1) in combination with IV infusion of commonly used chemotherapy agents, including gemcitabine, paclitaxel, and carboplatin. (NCT02272790)
Timeframe: Pre-dose, 0.5 hr, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

Interventionhours (Median)
Arm A 800 mg/m² Gemcitabine2.00
Arm A 1000 mg/m² Gemcitabine2.02
Arm B4.08
Arm C3.15

[back to top]

Disease Control Rate (DCR)

The Disease Control Rate is defined as the proportion of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) according to RECIST v1.1 criteria. (NCT02272790)
Timeframe: Throughout the duration of the study (up to 19 months)

InterventionParticipants (Number)
Arm A3
Arm B27
Arm C19
Arm C212
Arm D-175 mg3
Arm D-225 mg5

[back to top]

Duration of Response (DoR)

Duration of Response (DoR) is defined as the time from first documented tumour response until the date of documented progression or death from any cause. (NCT02272790)
Timeframe: Throughout the duration of the study, approximately 19 months.

InterventionMonths (Median)
Arm A4.4
Arm B12.0
Arm CNA
Arm C210.4
Arm D-175 mgNA
Arm D-225 mgNA

[back to top]

Progression Free Survival (Median, 95% CI)

"Progression-free survival (PFS) was defined as the elapsed time from date of first dose of AZD1775 until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdrew from therapy or received another anti-cancer therapy prior to progression. Patients who had not progressed or died at the time of analysis were censored at the time of the latest date of assessment from their last evaluable RECIST assessment.~Progression-free survival was derived based on scan/assessment dates, not visit dates." (NCT02272790)
Timeframe: Throughout the Study, Approximately 4 years

InterventionMonths (Median)
Arm A1.7
Arm B5.5
Arm C4.2
Arm C212.0
Arm D-175 mg2.7
Arm D-225 mgNA

[back to top]

Multiple Dose Adavosertib Tmax

The time to reach maximum plasma concentration of adavosertib after multiple oral doses (Cycle 1 Day 3) in combination with IV infusion of 40 mg/m² pegylated liposomal doxorubicin. (NCT02272790)
Timeframe: Pre-dose, 1 hr, 2 hr, 4 hr, 6 hr, and 8 hr

Interventionhours (Median)
Arm D 175 mg3.92
Arm D 225 mg2.88

[back to top]

Gynecologic Cancer Intergroup (GCIG) CA-125 Response

The GCIG CA-125 response is defined as the proportion of patients achieving a 50% reduction in CA-125 levels from baseline, if baseline level is ≥2 x the upper limit of normal (ULN) within 2 weeks prior to starting treatment. Response must be confirmed and maintained for at least 28 days. (NCT02272790)
Timeframe: Throughout the study, approximately 4 years

InterventionPercent (Number)
Arm A25.0
Arm B53.6
Arm C26.7
Arm C263.6
Arm D-175 mg25.0
Arm D-225 mg25.0

[back to top]

The Number of Patients Experiencing Treatment-emergent Adverse Events (TEAEs) by Maximum CTCAE Grade.

"The number of patients experiencing at least one treatment-related adverse event (TEAE) by maximum CTCAE grade.~Severity Grade 1 = Mild; Severity Grade 2 = Moderate; Severity Grade 3 = Severe; Severity Grade 4 = Life Threatening; Severity Grade 5 = Fatal" (NCT02272790)
Timeframe: Throughout the duration of the study (up to 19 months)

,,,,,
InterventionParticipants (Number)
Number of patients with ≥1 TEAE of max Grade 1Number of patients with ≥1 TEAE of max Grade 2Number of patients with ≥1 TEAE of max Grade 3Number of patients with ≥1 TEAE of max Grade 4Number of patients with ≥1 TEAE of max Grade 5
Arm A01260
Arm B2119151
Arm C051080
Arm C200480
Arm D-175 mg03300
Arm D-225 mg04020

[back to top] [back to top]

2 - Year Progression Free Survival

Number of participants progression free 2 years after registration. (NCT02272816)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
Carboplatin AUC-1046

[back to top]

Part A: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344

Accumulation ratio of AUC0-t was calculated as AUC0-t, after dosing on Day 8 divided by AUC0-t, after dosing on Day 1 of Cycle 1. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionratio (Geometric Mean)
Part A: M4344 10 mg BIWNA
Part A: M4344 20 mg BIWNA
Part A: M4344 40 mg BIWNA
Part A: M4344 80 mg BIWNA
Part A: M4344 160 mg BIWNA
Part A: M4344 300 mg BIWNA
Part A: M4344 450 mg BIW0.955
Part A: M4344 700 mg BIW1.46
Part A: M4344 1050 mg BIW1.36
Part A: M4344 1200 mg BIW1.89

[back to top]

Part A2: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

SD is defined as neither sufficient increase to qualify for progression disease (PD) nor sufficient shrinkage to qualify for partial response (PR). PR: at least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 6.2 years

InterventionParticipants (Count of Participants)
Part A2: M4344 100 mg BID1
Part A2: M4344 150 mg QD1
Part A2: M4344 250 mg QD4
Part A2: M4344 350 mg QD2

[back to top]

Part A2: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 39)

InterventionParticipants (Count of Participants)
Part A2: M4344 100 mg BID7
Part A2: M4344 150 mg QD5
Part A2: M4344 250 mg QD7
Part A2: M4344 350 mg QD7

[back to top]

Part A2: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 6.2 years

Interventionpercentage of participants (Number)
Part A2: M4344 100 mg BID0.0
Part A2: M4344 150 mg QD0.0
Part A2: M4344 250 mg QD0.0
Part A2: M4344 350 mg QD0.0

[back to top]

Part B1: Apparent Clearance (CL/f) of M4344

CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionliter per hour (Geometric Mean)
Part B1: M4344 350 mg + CarboplatinNA
Part B1: M4344 400 mg + Carboplatin1090
Part B1: M4344 500 mg + Carboplatin194

[back to top]

Part B1: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionliters (Geometric Mean)
Part B1: M4344 350 mg + CarboplatinNA
Part B1: M4344 400 mg + Carboplatin1620
Part B1: M4344 500 mg + Carboplatin1060

[back to top]

Part B1: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionng*h/mL (Geometric Mean)
Part B1: M4344 350 mg + Carboplatin392
Part B1: M4344 400 mg + Carboplatin268
Part B1: M4344 500 mg + Carboplatin1450

[back to top]

Part B1: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionng*h/mL (Geometric Mean)
Part B1: M4344 350 mg + CarboplatinNA
Part B1: M4344 400 mg + Carboplatin368
Part B1: M4344 500 mg + Carboplatin2570

[back to top]

Part B1: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344

AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionng*h/mL/mg (Geometric Mean)
Part B1: M4344 350 mg + CarboplatinNA
Part B1: M4344 400 mg + Carboplatin0.920
Part B1: M4344 500 mg + Carboplatin5.15

[back to top]

Part B1: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344

AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionng*h/mL/mg (Geometric Mean)
Part B1: M4344 350 mg + Carboplatin1.12
Part B1: M4344 400 mg + Carboplatin0.669
Part B1: M4344 500 mg + Carboplatin2.90

[back to top]

Part B1: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344

Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionng/mL/mg (Geometric Mean)
Part B1: M4344 350 mg + Carboplatin0.884
Part B1: M4344 400 mg + Carboplatin0.286
Part B1: M4344 500 mg + Carboplatin0.735

[back to top]

Part B1: Maximum Observed Plasma Concentration (Cmax) of M4344

Cmax was obtained directly from the plasma concentration versus time curve. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionng/mL (Geometric Mean)
Part B1: M4344 350 mg + Carboplatin309
Part B1: M4344 400 mg + Carboplatin114
Part B1: M4344 500 mg + Carboplatin367

[back to top]

Part B1: Maximum Tolerated Dose (MTD) of M4344 (Monotherapy) Administered in Combination With Carboplatin

MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks. (NCT02278250)
Timeframe: up to Cycle 1 (each cycle is of 21 days)

Interventionmg (Number)
Part B1: M4344NA

[back to top]

Part B1: Number of Participants With Clinically Relevant Findings in Vital Signs

Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator. (NCT02278250)
Timeframe: up to Safety follow-up (Week 92.3)

InterventionParticipants (Count of Participants)
Part B1: M4344 350 mg + Carboplatin0
Part B1: M4344 400 mg + Carboplatin0
Part B1: M4344 500 mg + Carboplatin0

[back to top]

Part B1: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)

ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by Investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported. (NCT02278250)
Timeframe: up to Safety follow-up (Week 92.3)

InterventionParticipants (Count of Participants)
Part B1: M4344 350 mg + Carboplatin0
Part B1: M4344 400 mg + Carboplatin0
Part B1: M4344 500 mg + Carboplatin0

[back to top]

Part B1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs. (NCT02278250)
Timeframe: up to Safety follow-up (Week 92.3)

InterventionParticipants (Count of Participants)
Part B1: M4344 350 mg + Carboplatin3
Part B1: M4344 400 mg + Carboplatin7
Part B1: M4344 500 mg + Carboplatin6

[back to top]

Part B1: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 5.2 years

Interventionpercentage of participants (Number)
Part B1: M4344 350 mg + Carboplatin0.0
Part B1: M4344 400 mg + Carboplatin14.3
Part B1: M4344 500 mg + Carboplatin0.0

[back to top]

Part B1: Terminal Elimination Half-Life (T1/2) of M4344

Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionhours (Geometric Mean)
Part B1: M4344 350 mg + CarboplatinNA
Part B1: M4344 400 mg + Carboplatin1.03
Part B1: M4344 500 mg + Carboplatin3.77

[back to top]

Part B1:Time to Reach Maximum Plasma Concentration (Tmax) of M4344

Tmax was obtained directly from the plasma concentration versus time curve. (NCT02278250)
Timeframe: Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 2 (each cycle is of 21 days)

Interventionhours (Median)
Part B1: M4344 350 mg + Carboplatin1.52
Part B1: M4344 400 mg + Carboplatin1.50
Part B1: M4344 500 mg + Carboplatin1.96

[back to top]

Part C: Number of Participants With Clinically Relevant Findings in Vital Signs

Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator. (NCT02278250)
Timeframe: up to Safety follow-up (Week 31.1)

InterventionParticipants (Count of Participants)
Part C: M4344 250 mg QD0

[back to top]

Part C: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)

ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported. (NCT02278250)
Timeframe: up to Safety follow-up (Week 31.1)

InterventionParticipants (Count of Participants)
Part C: M4344 250 mg QD6

[back to top]

Part C: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator

OR is defined as the confirmed assessment of best overall response of complete response (CR) or partial response (PR). CR is defined as disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 6.4 years

Interventionpercentage of participants (Number)
Part C: M4344 250 mg QD0.0

[back to top]

Part C: Progression-Free Survival (PFS) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 as Assessed by Investigator

PFS is defined as the time from start of study treatment to progression disease (PD) or death. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 6.4 years

Interventionmonths (Median)
Part C: M4344 250 mg QD1.6

[back to top]

Part A: Apparent Clearance (CL/f) of M4344

CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionliter per hour (Geometric Mean)
Cycle 1 Day 1
Part A: M4344 1200 mg BIW781

[back to top]

Part A: Apparent Clearance (CL/f) of M4344

CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,
Interventionliter per hour (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW597NA
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW464513
Part A: M4344 700 mg BIW409221
Part A: M4344 80 mg BIWNANA

[back to top]

Part A: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionliters (Geometric Mean)
Cycle 1 Day 1
Part A: M4344 1200 mg BIW4060

[back to top]

Part A: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,
Interventionliters (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW3970NA
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW14801620
Part A: M4344 700 mg BIW1960993
Part A: M4344 80 mg BIWNANA

[back to top]

Part A: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,,
Interventionnanogram*hour per milliliter (ng*h/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW13901550
Part A: M4344 1200 mg BIW22201880
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW948809
Part A: M4344 700 mg BIW18302670
Part A: M4344 80 mg BIWNANA

[back to top]

Part A: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344

AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose. AUC0-t/dose was measured in nanogram*hour per milliliter per milligram (ng*h/mL/mg). (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,,
Interventionng*h/mL/mg (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW1.321.47
Part A: M4344 1200 mg BIW1.851.57
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW2.111.80
Part A: M4344 700 mg BIW2.613.82
Part A: M4344 80 mg BIWNANA

[back to top]

Part A: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344

Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg). (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,,
Interventionng/mL/mg (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW0.3760.312
Part A: M4344 1200 mg BIW0.4800.405
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW0.8350.760
Part A: M4344 700 mg BIW0.7380.964
Part A: M4344 80 mg BIWNANA

[back to top]

Part A: Maximum Observed Plasma Concentration (Cmax) of M4344

Cmax was obtained directly from the plasma concentration versus time curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,,
Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW395328
Part A: M4344 1200 mg BIW576486
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW376342
Part A: M4344 700 mg BIW516675
Part A: M4344 80 mg BIWNANA

[back to top]

Part A: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)

Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 124.9)

,,,,,,,,,
InterventionParticipants (Count of Participants)
HematologyTotal Bilirubin
Part A: M4344 10 mg BIW00
Part A: M4344 1050 mg BIW06
Part A: M4344 1200 mg BIW04
Part A: M4344 160 mg BIW00
Part A: M4344 20 mg BIW00
Part A: M4344 300 mg BIW00
Part A: M4344 40 mg BIW00
Part A: M4344 450 mg BIW00
Part A: M4344 700 mg BIW05
Part A: M4344 80 mg BIW00

[back to top]

Part A: Terminal Elimination Half-Life (T1/2) of M4344

Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionhours (Geometric Mean)
Cycle 1 Day 1
Part A: M4344 1200 mg BIW3.60

[back to top]

Part A: Terminal Elimination Half-Life (T1/2) of M4344

Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,
Interventionhours (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW4.61NA
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW2.222.19
Part A: M4344 700 mg BIW3.333.11
Part A: M4344 80 mg BIWNANA

[back to top]

Part A: Maximum Tolerated Dose (MTD) of M4344 Administered Twice Weekly (BIW)

MTD as per NCI-CTCAE v4.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks. (NCT02278250)
Timeframe: up to Cycle 1 (each cycle is of 21 days)

Interventionmilligrams (mg) (Number)
Part A: M4344NA

[back to top]

Part C: Overall Survival (OS)

OS was defined as the time from treatment start to the date of death due to any cause. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date. OS was measured using Kaplan-Meier (KM) estimates. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 6.4 years

Interventionmonths (Number)
Participant 1Participant 2Participant 3Participant 4Participant 5Participant 6
Part C: M4344 250 mg QD1.910.791.613.982.532.63

[back to top] [back to top]

Part C: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)

Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death. (NCT02278250)
Timeframe: up to Safety follow-up (Week 31.1)

InterventionParticipants (Count of Participants)
Low lymphocytesLow hemoglobinTotal BilirubinAspartate AminotransferaseAlanine Aminotransferase
Part C: M4344 250 mg QD86743

[back to top]

Part C: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1

Confirmed BOR is defined as best response of any of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the treatment start date until documented disease progression. CR: Disappearance of all evidence of target/non-target lesions. PR: At least 30%reduction from baseline in sum of longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD: at least a 20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 6.4 years

InterventionParticipants (Count of Participants)
Complete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)Non-CR/Non-PDNon-evaluable
Part C: M4344 250 mg QD003802

[back to top]

Part A: Number of Participants With Clinically Relevant Findings in Vital Signs

Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings in vital signs were reported. Clinical relevance was decided by Investigator. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 124.9)

InterventionParticipants (Count of Participants)
Part A: M4344 10 mg BIW0
Part A: M4344 20 mg BIW0
Part A: M4344 40 mg BIW0
Part A: M4344 80 mg BIW0
Part A: M4344 160 mg BIW0
Part A: M4344 300 mg BIW0
Part A: M4344 450 mg BIW0
Part A: M4344 700 mg BIW0
Part A: M4344 1050 mg BIW0
Part A: M4344 1200 mg BIW0

[back to top]

Part A: Time to Reach Maximum Plasma Concentration (Tmax) of M4344

Tmax was obtained directly from the plasma concentration versus time curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,,,,,,,
Interventionhours (Median)
Cycle 1 Day 1Cycle 1 Day 8
Part A: M4344 10 mg BIWNANA
Part A: M4344 1050 mg BIW2.064.00
Part A: M4344 1200 mg BIW3.073.95
Part A: M4344 160 mg BIWNANA
Part A: M4344 20 mg BIWNANA
Part A: M4344 300 mg BIWNANA
Part A: M4344 40 mg BIWNANA
Part A: M4344 450 mg BIW1.511.22
Part A: M4344 700 mg BIW2.002.00
Part A: M4344 80 mg BIWNANA

[back to top]

Part A2: Apparent Clearance (CL/f) of M4344

CL/f was a measure of the rate at which a drug was metabolized or eliminated by normal biological processes. CL/f was calculated as Dose/AUC0-inf, where AUC0-inf was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity. AUC0-inf was calculated as AUC0-t + Clast pred/Lambda Z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the lower limit of quantification (LLQ) and Lambda Z was the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,
Interventionliter per hour (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A2: M4344 100 mg BID461424
Part A2: M4344 150 mg QD344239
Part A2: M4344 250 mg QD207302
Part A2: M4344 350 mg QD515NA

[back to top]

Part A2: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC0-t) of M4344

Area under the plasma concentration versus time curve from time zero to the last sampling time t at which the concentration was at or above the lower limit of quantification (LLOQ). AUC0-t was calculated according to the mixed log-linear trapezoidal rule. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,
Interventionng*h/mL (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A2: M4344 100 mg BID216236
Part A2: M4344 150 mg QD414627
Part A2: M4344 250 mg QD1230829
Part A2: M4344 350 mg QD703NA

[back to top]

Part A2: Dose Normalized Area Under the Plasma Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-t/Dose) of M4344

AUC0-t/Dose was defined as AUC from time of dosing to the time of the last measurable concentration divided by dose. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,
Interventionng*h/mL/mg (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A2: M4344 100 mg BID2.162.36
Part A2: M4344 150 mg QD2.764.18
Part A2: M4344 250 mg QD4.933.32
Part A2: M4344 350 mg QD2.01NA

[back to top]

Part A: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)

ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical significance was decided by investigator. Number of participants with clinically significant abnormalities in 12-Lead ECGs were reported. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 124.9)

InterventionParticipants (Count of Participants)
Part A: M4344 10 mg BIW0
Part A: M4344 20 mg BIW0
Part A: M4344 40 mg BIW0
Part A: M4344 80 mg BIW0
Part A: M4344 160 mg BIW0
Part A: M4344 300 mg BIW0
Part A: M4344 450 mg BIW0
Part A: M4344 700 mg BIW1
Part A: M4344 1050 mg BIW0
Part A: M4344 1200 mg BIW1

[back to top]

Part A: Number of Participants With Stable Disease (SD) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

SD is defined as neither sufficient increase to qualify for progression disease (PD) nor sufficient shrinkage to qualify for partial response (PR). PR: at least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. PD: at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 4.3 years

InterventionParticipants (Count of Participants)
Part A: M4344 10 mg BIW0
Part A: M4344 20 mg BIW1
Part A: M4344 40 mg BIW0
Part A: M4344 80 mg BIW0
Part A: M4344 160 mg BIW0
Part A: M4344 300 mg BIW0
Part A: M4344 450 mg BIW2
Part A: M4344 700 mg BIW2
Part A: M4344 1050 mg BIW1
Part A: M4344 1200 mg BIW1

[back to top]

Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal relationship with this treatment. Therefore, an AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, regardless if it is considered related to the medicinal product. Serious AE: AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs are defined as AEs that were reported or worsened on or after start of study drug dosing through the Safety Follow-up Visit. TEAEs included both serious TEAEs and non-serious TEAEs. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 124.9)

InterventionParticipants (Count of Participants)
Part A: M4344 10 mg BIW2
Part A: M4344 20 mg BIW1
Part A: M4344 40 mg BIW2
Part A: M4344 80 mg BIW1
Part A: M4344 160 mg BIW1
Part A: M4344 300 mg BIW2
Part A: M4344 450 mg BIW4
Part A: M4344 700 mg BIW12
Part A: M4344 1050 mg BIW10
Part A: M4344 1200 mg BIW7

[back to top]

Part A: Percentage of Participants With Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

The OR was defined as the confirmed assessment of best overall response (BOR) of partial response (PR),or complete response (CR) according to RECIST v1.1. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions. (NCT02278250)
Timeframe: Time from first dose of study treatment up to 4.3 years

Interventionpercentage of participants (Number)
Part A: M4344 10 mg BIW0.0
Part A: M4344 20 mg BIW0.0
Part A: M4344 40 mg BIW0.0
Part A: M4344 80 mg BIW0.0
Part A: M4344 160 mg BIW0.0
Part A: M4344 300 mg BIW0.0
Part A: M4344 450 mg BIW0.0
Part A: M4344 700 mg BIW0.0
Part A: M4344 1050 mg BIW0.0
Part A: M4344 1200 mg BIW0.0

[back to top]

Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve (Racc [AUC]) of M4344

Accumulation ratio of AUC was calculated as AUC, after dosing on Day 8 divided by AUC, after dosing on Day 1 of Cycle 1. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionratio (Geometric Mean)
Part A2: M4344 100 mg BID0.997
Part A2: M4344 150 mg QD1.32
Part A2: M4344 250 mg QD0.676
Part A2: M4344 350 mg QDNA

[back to top]

Part A2: Accumulation Ratio for Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (Racc [AUC0-t]) of M4344

Accumulation ratio of AUC0-t was calculated as AUC0-t, after dosing on Day 8 divided by AUC0-t, after dosing on Day 1 of Cycle 1. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 12 (in BID arms), 24 hours post-dose (in QD arms) on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionratio (Geometric Mean)
Part A2: M4344 100 mg BID1.00
Part A2: M4344 150 mg QD1.42
Part A2: M4344 250 mg QD0.672
Part A2: M4344 350 mg QDNA

[back to top]

Part A2: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M4344

Dose normalized was calculated as Cmax obtained directly from the concentration versus time curve divided by dose. Cmax/dose was measured in nanogram per milliliter per milligram (ng/mL/mg). (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,
Interventionng/mL/mg (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A2: M4344 100 mg BID1.111.14
Part A2: M4344 150 mg QD0.8291.63
Part A2: M4344 250 mg QD2.071.52
Part A2: M4344 350 mg QD0.758NA

[back to top]

Part A2: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344

Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 8 divided by Cmax, after dosing on Day 1 of Cycle 1. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionratio (Geometric Mean)
Part A2: M4344 100 mg BID1.08
Part A2: M4344 150 mg QD2.26
Part A2: M4344 250 mg QD0.733
Part A2: M4344 350 mg QDNA

[back to top]

Part A2: Apparent Volume of Distribution During Terminal Phase (Vz/f) of M4344

Vz/f: the distribution of a study drug between plasma and the rest of the body after oral dosing. For single dose Vz/f = Dose/(AUC0-inf*Lambda Z), where AUC0-inf = (AUC0-t + Clast pred/Lambda Z). Clastpred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration was at or above the LLOQ and Lambda Z = the apparent terminal rate constant determined from the terminal slope of the log-transformed plasma concentration curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)

Interventionliters (Geometric Mean)
Part A2: M4344 100 mg BID876
Part A2: M4344 150 mg QD1220
Part A2: M4344 250 mg QD519
Part A2: M4344 350 mg QD1760

[back to top]

Part A2: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)

Interventionng*h/mL (Geometric Mean)
Part A2: M4344 100 mg BID217
Part A2: M4344 150 mg QD436
Part A2: M4344 250 mg QD1210
Part A2: M4344 350 mg QD680

[back to top]

Part A2: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344

AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose. AUC0-inf/Dose was measured in nanogram*hour per milliliter per milligram (ng*h/mL/mg). (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)

Interventionng*h/mL/mg (Geometric Mean)
Part A2: M4344 100 mg BID2.17
Part A2: M4344 150 mg QD2.91
Part A2: M4344 250 mg QD4.84
Part A2: M4344 350 mg QD1.94

[back to top]

Part A2: Maximum Tolerated Dose (MTD) of M4344 Administered With a Dose Dense Schedule

MTD as per NCI-CTCAE v5.0 is defined as highest dose for a given schedule at which there is no more than 1 dose- limiting toxicity (DLT) in 6 participants. DLT: as related/possibly drug-related: Neutropenia Grade (Gr)4 for > 7 days duration/requiring hemopoietic growth factors; Febrile neutropenia; Infection with Gr3/4 neutropenia; Thrombocytopenia Gr3; Thrombocytopenia Gr4 for > 7 days duration/requiring hemopoietic growth factors; Gr3/4 toxicity to organs other than bone marrow; Gr3/4 increase in bilirubin unless increase is due to inhibition of bilirubin glucuronidation; Death due to drug-related complications; Cardiac: QTc prolongation, Gr2/greater ventricular arrhythmia, severe sustained/symptomatic sinus bradycardia, persistent supraventricular arrhythmia, Symptoms suggestive of congestive heart failure, Troponin-T level consistent with myocardial infarction; drug-related toxicity causes interruption of treatment for > 2 weeks. (NCT02278250)
Timeframe: up to Cycle 1 (each cycle is of 21 days)

Interventionmg (Number)
Part A2: M4344250

[back to top]

Part A2: Number of Participants With Clinically Relevant Findings in Vital Signs

Vital signs included body temperature, heart rate, systolic and diastolic blood pressure and respiration rate. Number of participants with clinically relevant findings were reported. Clinical relevance was decided by Investigator. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 39)

InterventionParticipants (Count of Participants)
Part A2: M4344 100 mg BID0
Part A2: M4344 150 mg QD0
Part A2: M4344 250 mg QD0
Part A2: M4344 350 mg QD0

[back to top]

Part A2: Maximum Observed Plasma Concentration (Cmax) of M4344

Cmax was obtained directly from the plasma concentration versus time curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,
Interventionng/mL (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A2: M4344 100 mg BID111114
Part A2: M4344 150 mg QD124244
Part A2: M4344 250 mg QD517379
Part A2: M4344 350 mg QD265NA

[back to top]

Part A2: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0)

Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v5.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 39)

,,,
InterventionParticipants (Count of Participants)
Low lymphocytesTotal BilirubinAspartate AminotransferaseAlanine Aminotransferase
Part A2: M4344 100 mg BID1322
Part A2: M4344 150 mg QD1212
Part A2: M4344 250 mg QD2300
Part A2: M4344 350 mg QD3343

[back to top]

Part A2: Terminal Elimination Half-Life (T1/2) of M4344

Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. T1/2 was calculated by natural log 2 divided by Lambda z. Lambda z was determined from the terminal slope of the log-transformed plasma concentration curve using linear regression method. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,
Interventionhours (Geometric Mean)
Cycle 1 Day 1Cycle 1 Day 8
Part A2: M4344 100 mg BID1.321.36
Part A2: M4344 150 mg QD2.471.31
Part A2: M4344 250 mg QD1.741.31
Part A2: M4344 350 mg QD2.37NA

[back to top]

Part A2: Time to Reach Maximum Plasma Concentration (Tmax) of M4344

Tmax was obtained directly from the plasma concentration versus time curve. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 12 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

,,,
Interventionhours (Median)
Cycle 1 Day 1Cycle 1 Day 8
Part A2: M4344 100 mg BID1.451.03
Part A2: M4344 150 mg QD1.621.28
Part A2: M4344 250 mg QD1.501.50
Part A2: M4344 350 mg QD1.10NA

[back to top]

Part B1: Number of Participants With Grade 3 or 4 (Greater Than [>] 20 Percent [%] of Total) in Laboratory Parameters Based on National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v4.0)

Laboratory parameters: hematology and chemistry. Blood samples were collected for analysis of following hematology parameters: Hemoglobin, Erythrocytes, mean corpuscular hemoglobin (MCH), MCH concentration, Mean corpuscular volume, Reticulocytes, Platelets, Leukocytes, Eosinophils, Basophils, Neutrophils, Lymphocytes, Monocytes. Blood samples were collected for analysis of following chemistry parameters: Glucose, Blood urea nitrogen/Urea, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Inorganic phosphate, Total bilirubin, Direct bilirubin, Total protein, Albumin, Creatine kinase, Alkaline phosphatase, Aspartate aminotransferase, Alanine aminotransferase, Lactate dehydrogenase, Uric acid, Thyroid stimulating hormone. Number of participants with Grade 3 or 4 (>20% of total) in laboratory parameters were reported as per NCI-CTCAE v4.0 graded from Grade 1 to 5. Grade 1: Mild, Grade 2: Moderate; Grade 3: Severe. Grade 4: Life-threatening and Grade 5: Death. (NCT02278250)
Timeframe: up to Safety follow-up (Week 92.3)

,,
InterventionParticipants (Count of Participants)
NeutrophilsPlateletsLow hemoglobinLow LeukocytesLow lymphocytesChemistry
Part B1: M4344 350 mg + Carboplatin111010
Part B1: M4344 400 mg + Carboplatin134130
Part B1: M4344 500 mg + Carboplatin531410

[back to top]

Part A2: Number of Participants With Clinically Significant Abnormalities in 12-Lead Electrocardiogram (ECGs)

ECG parameters included PR interval, RR interval, QT interval, QRS duration, QTc intervals (derived using Fridericia's correction method) and heart rate. A 12-lead ECG was recorded with the participant in a supine position after a rest of at least 5 minutes using an ECG machine. Clinical Significance was determined by investigator. Number of participants with clinically significant abnormalities in 12-lead ECGs were reported. (NCT02278250)
Timeframe: up to safety follow-up visit (Week 39)

InterventionParticipants (Count of Participants)
Part A2: M4344 100 mg BID0
Part A2: M4344 150 mg QD0
Part A2: M4344 250 mg QD0
Part A2: M4344 350 mg QD0

[back to top]

Part A: Dose Normalized Area Under the Concentration-Time Curve Over Entire Dosing Time Period From Time Zero Extrapolated to Infinity (AUC0-inf/Dose) of M4344

AUC0-inf/Dose was defined as AUC extrapolated to infinity divided by dose. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)

Interventionng*h/mL/mg (Geometric Mean)
Part A: M4344 10 mg BIWNA
Part A: M4344 20 mg BIWNA
Part A: M4344 40 mg BIWNA
Part A: M4344 80 mg BIWNA
Part A: M4344 160 mg BIWNA
Part A: M4344 300 mg BIWNA
Part A: M4344 450 mg BIW2.16
Part A: M4344 700 mg BIW2.45
Part A: M4344 1050 mg BIW1.68
Part A: M4344 1200 mg BIW1.28

[back to top]

Part A: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4344

AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated plasma concentration at the last sampling time point at which the measured plasma concentration is at or above the Lower Limit of quantification (LLOQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured plasma concentrations of the terminal log-linear phase. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Cycle 1 Day 1 (each cycle is of 21 days)

Interventionng*h/mL (Geometric Mean)
Part A: M4344 10 mg BIWNA
Part A: M4344 20 mg BIWNA
Part A: M4344 40 mg BIWNA
Part A: M4344 80 mg BIWNA
Part A: M4344 160 mg BIWNA
Part A: M4344 300 mg BIWNA
Part A: M4344 450 mg BIW971
Part A: M4344 700 mg BIW1710
Part A: M4344 1050 mg BIW1760
Part A: M4344 1200 mg BIW1540

[back to top]

Part A: Accumulation Ratio for Maximum Observed Plasma Concentration (Racc [Cmax]) of M4344

Accumulation ratio of Cmax was calculated as Cmax, after dosing on Day 8 divided by Cmax, after dosing on Day 1 of Cycle 1. (NCT02278250)
Timeframe: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 8 and 24 hours post-dose on Day 1 and Day 8 of Cycle 1 (each cycle is of 21 days)

Interventionratio (Geometric Mean)
Part A: M4344 10 mg BIWNA
Part A: M4344 20 mg BIWNA
Part A: M4344 40 mg BIWNA
Part A: M4344 80 mg BIWNA
Part A: M4344 160 mg BIWNA
Part A: M4344 300 mg BIWNA
Part A: M4344 450 mg BIW0.988
Part A: M4344 700 mg BIW1.19
Part A: M4344 1050 mg BIW1.01
Part A: M4344 1200 mg BIW1.55

[back to top]

Progression-free Survival (PFS) Among All Randomized Particiapants Who Received at Least One Dose of Blinded Study Therapy Using Modified World Health Organization (mWHO) Criteria

PFS is defined as the time between the date of randomization and the date of progression per mWHO criteria or death, whichever occurs first. A participant who died without reported progression per mWHO criteria was considered to have progressed on the date of death. For those participants who remained alive and had not progressed, PFS was censored on the date of last evaluable tumor assessment. For those participants who remained alive and had no recorded post-baseline tumor assessment, PFS was censored on the day of randomization. (NCT02279732)
Timeframe: Approximately 43 months post study start

Interventionmonths (Median)
Ipi + PAC/CARNA
Placebo + PAC/CARNA

[back to top]

Overall Survival of All Randomized Participants

OS is defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive. (NCT02279732)
Timeframe: Approximately 43 months post study start

Interventionmonths (Median)
Ipi + PAC/CARNA
Placebo + PAC/CARNA

[back to top]

Overall Survival (OS) of All Randomized Participants Who Received at Least One Dose of Blinded Study Therapy

OS is defined as the time from the date of randomization until the date of death. For those participants who have not died, OS was censored on the last date the participant was known to be alive. (NCT02279732)
Timeframe: Approximately 43 months post study start

Interventionmonths (Median)
Ipi + PAC/CARNA
Placebo + PAC/CARNA

[back to top]

Percentage of Participants Who Achieved a Best Overall Response of Complete Response or Partial Response According to RECIST 1.1 Guidelines

Overall tumor response is defined as the percentage of participants who achieved an objective confirmed CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions from baseline) according to RECIST V1.1 guidelines, compared with baseline where baseline was the last computed tomography (CT) scan obtained prior to or on Day 1 of study treatment. (NCT02289456)
Timeframe: Response assessments were evaluated every 2 cycles; up to the clinical cut-off date of 24 February 2017; maximum treatment duration on study was 14.1 months

InterventionPercentage of participants (Number)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel30.0

[back to top]

Percentage of Protocol Dose

The percentage of protocol specified dose administered during the induction and monotherapy periods. Percentage of protocol dose = (dose intensity / protocol weekly dose) * 100%; the protocol weekly dose of nab-paclitaxel is 66.67 mg/m2/week; the protocol weekly dose of carboplatin was 1.67 mg*min/mL/week. (NCT02289456)
Timeframe: From Day 1 of study drug treatment to end of study drug treatment; up to clinical data cut-off date of 24 February 2017; ; maximum treatment duration was 14.1 months.

,
InterventionPercentage of Protocol Dose (Median)
nab-PaclitaxelCarboplatin
Induction Period: Nab-Paclitaxel and/or Carboplatin82.62080.630
Monotherapy Period: Nab-Paclitaxel71.185NA

[back to top]

Kaplan Meier Estimate of Progression-Free Survival (PFS)

Progression-free survival was defined as the time in months from day 1 of treatment to the date of disease progression based on the investigator's assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria (documented by radiological assessment) or death (any cause) on or prior to the clinical cut-off date, which ever occurred earlier. RECIST V1.1 criteria includes: - Complete Response (CR) is the disappearance of all target lesions; - Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions from baseline; - Stable Disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease (PD); - Progressive Disease is at least a 20% increase in the sum of diameters of target lesions from nadir (NCT02289456)
Timeframe: From Day 1 of study drug treatment to the date of disease progression; up to the clinical cut-off date of 24 February 2017; maximum treatment duration on study was 14.1 months

Interventionmonths (Median)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel4.40

[back to top]

Dose Intensity of Nab-Paclitaxel During the Entire Study

Dose intensity for nab-paclitaxel during the entire study period was (mg/m^2/week) = [cumulative dose for nab-paclitaxel in mg/m^2] / [nab-paclitaxel dosing period in weeks] (NCT02289456)
Timeframe: From Day 1 of study treatment to end of study treatment; maximum treatment duration on study was 14.1 months

Interventionmg/m^2/week (Mean)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel52.173

[back to top]

Kaplan Meier Estimate of Overall Survival (OS)

Overall survival was defined as the time in months between day 1 of treatment and death from any cause). Participants who were still alive as of the clinical cut-off date had their OS censored at the date of last contact or clinical cut-off, whichever was earlier. Participants who were lost to follow-up prior to the end of the study or who were withdrawn from the study were censored at the time of last contact. (NCT02289456)
Timeframe: From Day 1 of study treatment to death from any cause; up to the clinical cut-off date of 24 February 2017; maximum treatment duration on study was 14.1 months

Interventionmonths (Median)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel7.66

[back to top]

Kaplan Meier Estimate of Duration of Response

Duration of overall response was measured from the time measurement criteria were first met for CR (the disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions from baseline), whichever was first recorded, until the first date that recurrent disease or PD (at least a 20% increase in the sum of diameters of target lesions from nadir) was radiologically documented (taking as reference for PD the smallest measurements recorded on study). Median and 95% CI were estimated based on the Kaplan-Meier method. (NCT02289456)
Timeframe: From Day 1 of study drug treatment to the date of first occurrence of CR or PR; up to the clinical cut-off date of 24 February 2017; maximum treatment duration on study was 14.1 months

InterventionMonths (Median)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel6.83

[back to top]

Percentage of Participants With Dose Reductions During the Entire Study

A dose reduction occurs when the dose assigned at a visit was lower than the dose assigned at the previous visit. Dose reductions are typically caused by clinically significant laboratory abnormalities and/or treatment emergent adverse events or toxicities. (NCT02289456)
Timeframe: From day 1 of IP until 28 days after the last dose of IP; maximum treatment duration was 14.1 months during the entire study

InterventionPercentage of Participants (Number)
nab-PaclitaxelCarboplatin
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel32.527.5

[back to top]

Number of Participants With TEAEs During the Induction and Monotherapy Periods

Treatment-emergent adverse events were defined as any adverse event or serious adverse event that occurred or worsened on or after the day of the first dose of the IP through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. The severity of AEs were graded based on National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0 and the scale: Grade 1 = Mild l intervention/therapy required Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death. (NCT02289456)
Timeframe: From date of the first dose of IP until 28 days after the last IP dose and SAEs made known to the investigator any time thereafter that are suspected of being related to IP; up to cutoff date of 24 Feb 2017; maximum treatment duration was 14.1 months

,
InterventionParticipants (Count of Participants)
TEAESerious TEAEGrade 1/2 TEAEGrade 3/4 TEAEGrade 3 or Higher TEAETreatment-Related TEAETreatment-Related Serious TEAETEAE With Action to Reduce/Interrupt IPTreatment-Related to Reduce or Interrupt IPTEAE with Action Taken to Withdraw IPTreatment-Related TEAE Action to Halt IPTEAE with Fatal OutcomeTreatment-Related TEAE with Fatal Outcome
Induction Period: Nab-Paclitaxel and/or Carboplatin40203930303813252211810
Monotherapy Period: Nab-Paclitaxel1441477120321100

[back to top]

Time to Response

Time to response was defined as the time from Day 1 of study treatment to the first occurrence of response (CR or PR) according to RECIST v1.1 guidelines. RECIST V1.1 criteria includes: - A Complete Response (CR) is the disappearance of all target lesions; - A Partial Response (PR) is at least a 30% decrease in the sum of diameters of target lesions from baseline (NCT02289456)
Timeframe: From Day 1 of study drug treatment to the date of first occurrence of CR or PR; up to the clinical cut-off date of 24 February 2017; maximum treatment duration on study was 14.1 months

InterventionMonths (Median)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel2.00

[back to top]

Percentage of Participants Who Discontinued Study Treatment During the Induction Period Due to Treatment Emergent Adverse Events (TEAEs).

Treatment-emergent adverse events were defined as any adverse event (AE) or serious adverse event (SAE) that occurred or worsened on or after the day of the first dose of the investigational product through 28 days after the last dose of IP. In addition, any SAE with an onset date more than 28 day after the last dose of IP that was assessed by the investigator as related to IP was considered a TEAE. A participant met the primary endpoint if: an AE was the reason for discontinuation as recorded in the electronic Case Report Form (eCRF) and the participant had no doses administered beyond Cycle 4. 95% confidence interval for the percentage was calculated using the Clopper Pearson method. (NCT02289456)
Timeframe: From date of the first dose of IP until 28 days after the last dose of IP during induction and SAEs made known to the investigator any time thereafter that are suspected of being related to IP; maximum treatment duration during induction was 3.9 months

InterventionPercentage of Participants (Number)
(Induction Period) Nab-Paclitaxel and Carboplatin27

[back to top]

Percentage of Participants Who Discontinued Study Treatment During the Induction Period (Discontinuation Rate)

Discontinuation Rate was measured as Percentage of Participants who Discontinued Study Treatment During the Induction Period (NCT02289456)
Timeframe: From date of the first dose of IP until 28 days after the last dose of IP during induction and SAEs made known to the investigator any time thereafter that are suspected of being related to IP; maximum treatment duration during induction was 3.9 months

InterventionPercentage of Participants (Number)
(Induction Period) Nab-Paclitaxel and Carboplatin60.0

[back to top]

Dose Intensity of Carboplatin During the Entire Study

Dose intensity for carboplatin during the entire study period was (mg*min/mL/week) = [cumulative dose for carboplatin in mg*min/mL] / [carboplatin dosing period in weeks]. (NCT02289456)
Timeframe: From Day 1 of study treatment to end of study treatment; maximum treatment duration on study was 14.1 months

Interventionmg*min/mL/week (Mean)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel1.170

[back to top]

Percentage of Participants Who Achieved a Complete Response or Partial Response or Continued Stable Disease (Disease Control Rate)

Disease control rate was defined as the percentage of participants who had continued stable disease, complete or partial response during the course of the study, according to RECIST v1.1 guidelines, as evaluated by the investigator. RECIST V1.1 criteria includes: - Complete Response is the disappearance of all target lesions; - Partial Response is at least a 30% decrease in the sum of diameters of target lesions from baseline; - Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase of lesions to qualify for progressive disease; - Progressive Disease is at least a 20% increase in the sum of diameters of target lesions from nadir (NCT02289456)
Timeframe: Response assessments were evaluated every 6 weeks; up to the clinical cut-off date of 24 February 2017; maximum treatment duration on study was 14.1 months

InterventionPercentage of Participants (Number)
Nab-Paclitaxel/Carboplatin Followed by Nab-Paclitaxel75.0

[back to top]

Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)

"A DLT was defined as any of the following drug-related toxicities, graded according to the Common Toxicity Criteria for Adverse Events (CTCAE), V.4.0:~Events associated with treatment delay >14 days in initiating Cycle 2 therapy:~Grade 4 thrombocytopenia, neutropenia, or febrile neutropenia, or Grade 3 febrile neutropenia with fever for > 7 days~Grade ≥ 3 non-hematologic toxicity with ≥ 2 grade increase from baseline and attributed to veliparib treatment, excluding nausea or vomiting for ≤ 48 hours or inadequately treated, electrolyte abnormalities resolving in ≤ 24 hours, hypersensitivity reactions or alopecia~Grade 2 non-hematologic toxicity of ≥ 2 grade increase from baseline, attributed to veliparib treatment requiring delay of >14 days in initiation of Cycle 2~Any toxicity of ≥ 2-grade increase from baseline, attributed to veliparib and requiring a dose modification in Cycle 1 or omission of carboplatin, >1 daily etoposide dose, or >30% veliparib doses in Cycle 1" (NCT02289690)
Timeframe: Cycle 1 Day -2 to pre-dose on Cycle 2 Day 1 (23 days)

InterventionParticipants (Count of Participants)
Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide1
Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide0
Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide1

[back to top]

Phase 1: Maximum Observed Plasma Concentration (Cmax) of Veliparib

Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionμg/mL (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide0.620
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide1.00
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide1.39
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide1.44
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide1.99

[back to top]

Phase 1: Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionμg/mL (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)16.9
Etoposide Cycle 2 Day 1 (No Veliparib)16.4

[back to top]

Phase 1: Dose-normalized Maximum Observed Plasma Concentration of Veliparib

"Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL.~Dose normalized Cmax is calculated as Cmax / veliparib dose in mg." (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Intervention(ng/mL)/mg (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide7.75
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide8.35
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide8.66
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide7.19
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide8.31

[back to top]

Phase 1: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionμg*h/mL (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)112
Etoposide Cycle 2 Day 1 (No Veliparib)99.5

[back to top]

Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-t) is calculated as AUC(0-t) / etoposide dose in mg/m². (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Intervention(ng*h/mL)/(mg/m²) (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)1020
Etoposide Cycle 2 Day 1 (No Veliparib)952

[back to top]

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Etoposide With and Without Veliparib

Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionhours (Median)
Etoposide Cycle 1 Day 1 (With Veliparib)0.9
Etoposide Cycle 2 Day 1 (No Veliparib)0.9

[back to top]

Phase 1: Dose-normalized Maximum Observed Plasma Concentration (Cmax) of Etoposide With and Without Veliparib

Etoposide plasma concentrations were determined using liquid chromatography with tandem mass spectrometric detection with a lower limit of quantitation 160 ng/mL. Dose normalized Cmax is calculated as Cmax / etoposide dose in mg/m². (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Intervention(ng/mL)/(mg/m²) (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)169
Etoposide Cycle 2 Day 1 (No Veliparib)170

[back to top]

Phase 1: Terminal Phase Elimination Half-life (t1/2) of Etoposide With and Without Veliparib

The terminal half-life of etoposide was estimated using using non-compartmental methods. Values reported represent the harmonic mean ± pseudo-standard deviation. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionhours (Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)5.7
Etoposide Cycle 2 Day 1 (No Veliparib)5.0

[back to top]

Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose of Veliparib

The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. Dose normalized AUC(0-8) is calculated as AUC(0-8) / veliparib dose in mg. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Intervention(ng*h/mL)/mg (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide39.8
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide35.3
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide46.9
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide33.3
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide38.7

[back to top]

Phase 1: Dose-normalized Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose of Veliparib

The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. Dose normalized AUC(0-12) is calculated as AUC(0-12) / veliparib dose in mg. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Intervention(ng*h/mL)/mg (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide50.9
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide43.8
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide60.7
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide41.7
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide48.5

[back to top]

Phase 1: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC[0-t]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to the last measurable concentration (24 hours) of etoposide was estimated using using non-compartmental methods. (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Interventionμg*h/mL (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)102
Etoposide Cycle 2 Day 1 (No Veliparib)94.7

[back to top]

Phase 2: Progression-free Survival

"Progression-free survival (PFS) is defined as the time from the date of randomization to the date of earliest radiographic disease progression or death provided no radiographic disease progression occurred.~If a participant did not have an event of disease progression and had not died on or prior to the cutoff for PFS analysis, the participant's data was censored at the date of their last disease assessment or randomization date provided participant did not have any post-baseline disease assessment.~Disease assessments were performed using computed tomography according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.~Progressive Disease (PD) was defined as at least a 20% increase in the size of target lesions and an absolute increase of at least 5 mm taking as reference the smallest lesion size recorded since the treatment started (baseline or after), or the appearance of one or more new lesions." (NCT02289690)
Timeframe: From randomization up to the date the 126th PFS event was reached; Median time on follow-up was 7.3, 7.1, and 8.9 months in each treatment group respectively.

Interventionmonths (Median)
Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib5.8
Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo5.7
Phase 2: Placebo + Carboplatin/Etoposide -> Placebo5.6

[back to top]

Phase 2: Overall Survival

Overall survival (OS) is defined as the time from the date of randomization to the date of death. If a participant did not die on or prior to the cut-off for OS analysis, the participant's data were censored at the date of their last known alive date, which is defined as the last date of the last survival follow-up visit, the start date of the last AE, the start date or end date of the last dose of any study drugs, the last lab and vital sign collection date, or the last disease assessment date, whichever occurred last. (NCT02289690)
Timeframe: From randomization until the end of study; median time on follow-up was 10.0, 8.6, and 11.7 months in each treatment group respectively.

Interventionmonths (Median)
Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib10.1
Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo10.0
Phase 2: Placebo + Carboplatin/Etoposide -> Placebo12.4

[back to top]

Phase 2: Objective Response Rate

"Objective response rate (ORR) is defined as the percentage of participants with objective response (confirmed) as assessed by the investigator using RECIST version 1.1. Objective response includes both complete response (CR) and partial response (PR). Response must be confirmed at a subsequent tumor assessment at least 28 days apart. Participants with no post-baseline confirmed response were counted as non-responders.~CR: Disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. No new lesions.~PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, and no new lesions." (NCT02289690)
Timeframe: Tumor assessments were performed every 6 weeks for the first 30 weeks and every 9 weeks thereafter until disease progression; median time on follow-up was 7.3, 7.1, and 8.9 months in each group respectively.

Interventionpercentage of participants (Number)
Phase 2: Veliparib + Carboplatin/Etoposide -> Veliparib77.0
Phase 2: Veliparib + Carboplatin/Etoposide -> Placebo59.3
Phase 2: Placebo + Carboplatin/Etoposide -> Placebo63.9

[back to top]

Phase 1: Time to Maximum Observed Plasma Concentration (Tmax) of Veliparib

Plasma concentrations of veliparib were determined using a validated online solid-phase extraction followed by high-performance liquid chromatography with tandem mass spectrometric detection (HPLC LC-MS/MS). The lower limit of quantitation (LLOQ) for veliparib was established at ≥ 1.05 ng/mL. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionhours (Median)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide2.0
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide1.0
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide1.5
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide2.0
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide1.0

[back to top]

Phase 1: Number of Participants With Adverse Events

"The intensity of each adverse event (AE) was assessed utilizing the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0, and according to the following: Grade 1 (Mild): AE is transient and easily tolerated by the participant; Grade 2 (Moderate): AE causes the participant discomfort and interrupts the participant's usual activities; Grade 3/4 (Severe): The adverse event causes considerable interference with the participant's usual activities and may be incapacitating or life-threatening; Grade 5: Death.~Serious adverse events were those that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization, resulted in congenital anomaly, or persistent or significant disability/incapacity." (NCT02289690)
Timeframe: From first dose of any study drug to 30 days after the last dose; the median duration of treatment with veliparib across all groups in Phase 1 was 127.5 days.

,,,,,,
InterventionParticipants (Count of Participants)
Any adverse eventAny AE Grade 3/4Any serious adverse eventAny fatal adverse event
Phase 1: Veliparib 120 mg BID 7 Days + Carboplatin/Etoposide3310
Phase 1: Veliparib 160 mg BID 7 Days + Carboplatin/Etoposide4431
Phase 1: Veliparib 200 mg BID 7 Days + Carboplatin/Etoposide3321
Phase 1: Veliparib 240 mg BID 14 Days + Carboplatin/Etoposide141460
Phase 1: Veliparib 240 mg BID 21 Days + Carboplatin/Etoposide4430
Phase 1: Veliparib 240 mg BID 7 Days + Carboplatin/Etoposide8730
Phase 1: Veliparib 80 mg BID 7 Days + Carboplatin/Etoposide4430

[back to top]

Phase 1: Dose-normalized Area Under the Concentration-time Curve From Time 0 to Infinity (AUC[0-∞]) of Etoposide With and Without Veliparib

The area under the plasma concentration-time curve from 0 to infinity for etoposide was estimated using using non-compartmental methods. Dose normalized AUC(0-∞) is calculated as AUC(0-∞) / etoposide dose in mg/m². (NCT02289690)
Timeframe: Cycle 1 Day 1 (coadministered with veliparib and carboplatin), and on Cycle 2 Day 1 (co-administered with carboplatin but in the absence of veliparib) at 55 minutes (5 minutes before the end of infusion) and 3, 5, 8, and 24 hours post-dose.

Intervention(ng*h/mL)/(mg/m²) (Geometric Mean)
Etoposide Cycle 1 Day 1 (With Veliparib)1120
Etoposide Cycle 2 Day 1 (No Veliparib)1020

[back to top]

Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose (AUC[0-8]) of Veliparib

The area under the plasma concentration-time curve from time 0 to 8 hours post-dose for veliparib was estimated using non-compartmental methods. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionμg*h/mL (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide3.18
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide4.24
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide7.51
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide6.66
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide9.29

[back to top]

Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours Post-dose (AUC[0-12]) of Veliparib

The area under the plasma concentration-time curve from time 0 to 12 hours post-dose for veliparib was estimated using non-compartmental methods. AUC(0-12) was calculated by assuming the concentration at 12 hours post-dose was the same as the pre-dose concentration. (NCT02289690)
Timeframe: Cycle 1 Day 1 predose and at 1, 2, 3, 5, 8, and 24 hours post-dose

Interventionμg*h/mL (Geometric Mean)
Phase 1: Veliparib 80 mg BID + Carboplatin/Etoposide4.07
Phase 1: Veliparib 120 mg BID + Carboplatin/Etoposide5.25
Phase 1: Veliparib 160 mg BID + Carboplatin/Etoposide9.71
Phase 1: Veliparib 200 mg BID + Carboplatin/Etoposide8.35
Phase 1: Veliparib 240 mg BID + Carboplatin/Etoposide11.6

[back to top]

Times to Onset of CTCAE Grade 2+ PN

Compare time to grade 2+ CIPN between GSH and placebo arms. (NCT02311907)
Timeframe: Up to 1 year

Interventiondays (Median)
A (Glutathione, Carboplatin)140
B (Placebo, Paclitaxel)234

[back to top]

Change in Patient Reported Quality of Life as Assessed by Functional Assessment of Cancer Therapy-Ovarian (FACT-O) and Patient Daily-symptom Questionnaires Over Time.

Quality of life was measured by FACT-O (on a 0 to 100 scale, higher scores represent better life quality) from baseline and at the end of TAXOL/CBDCA. The change in Quality of Life was calculated as the difference between baseline measure and end of treatment measure (with range from -100 to 100). A negative change represents a worsening in QOL from baseline to one year. Abbreviations used: Change from Baseline (chg from bsl) (NCT02311907)
Timeframe: Baseline to 1 year

,
Interventionunits on a scale (Median)
FACT-O Physical Subscale Chg from BslFACT-O Social/Family Subscale Chg from BslFACT-O Emotional Subscale Chg from BslFACT-O Functional Subscale Chg from BslFACT-O Additional Concerns Subscale Chg from BslFACT-O Total Score Chg from Bsl
A (Glutathione, Carboplatin)-14.3-4.28.30.0-2.30.3
B (Placebo, Paclitaxel)-8.90.04.25.14.84.4

[back to top]

Paclitaxel Acute Pain Syndrome Incidence and Severity Between GSH and Placebo Arms

Descriptive statistics will be used to describe TAXOL/CBDCA acute pain syndrome incidence/severity between GSH and placebo arms. Pain was scored on a scale from 0-10, where 0 = 'No aches or pains' and 10 = 'Aches or pains as bad as can be.' (NCT02311907)
Timeframe: Up to 1 year

Interventionunits on a scale (Median)
A (Glutathione, Carboplatin)2.0
B (Placebo, Paclitaxel)2.0

[back to top]

Paclitaxel/Carboplatin (PC) Induced Peripheral Neuropathy as Assessed by EORTC QLQ-CIPN20 (European Organization for Research and Treatment of Cancer (EORTC), Quality of Life (QLQ), Chemotherapy Induced Peripheral Neuropathy 20 (CIPN20)).

The CIPN sensory subscale will be calculated by standard scoring algorithm and converted to 0-100 scale (higher scores indicated less symptoms and better quality of life). Generalized linear models (repeated measures analysis of variance [ANOVA] if data are complete) will be used to compare the CIPN between Glutathione (GSH) and placebo arms. (NCT02311907)
Timeframe: Every 28 day cycle, up to 6 cycles.

InterventionUnits on a scale 1-100 (Least Squares Mean)
A (Glutathione, Carboplatin)83.7
B (Placebo, Paclitaxel)82.1

[back to top]

Percentage of Patients Delaying PC Chemotherapy Secondary to PN

Patients delaying TAXOL/CBDCA secondary to peripheral neuropathy between GSH and placebo arms. (NCT02311907)
Timeframe: Up to 1 year

InterventionPercentage of participants (Number)
A (Glutathione, Carboplatin)1.1
B (Placebo, Paclitaxel)0

[back to top]

Recurrence-free Survival (for Patients Without Clinical Evidence of Disease)

A log-rank test and a Kaplan-Meier curve will be used to compare the recurrence free survival between GSH and placebo arms (for ovarian/fallopian tube/primary peritoneal patients only). (NCT02311907)
Timeframe: Up to 1 year

InterventionMedian survival time in days (Median)
A (Glutathione, Carboplatin)NA
B (Placebo, Paclitaxel)NA

[back to top]

Times to Onset of CTCAE Grade 3+ PN

Time to grade 3+ CIPN between GSH and placebo arms. (NCT02311907)
Timeframe: Up to 5 years from registration

Interventiondays (Median)
A (Glutathione, Carboplatin)NA
B (Placebo, Paclitaxel)NA

[back to top]

Percentage of Patients Undergoing Dose Reductions Secondary to PCI PN

Proportion of patients requiring chemotherapy dose reductions secondary to TAXOL/CBDCA induced peripheral neuropathy between GSH and placebo arms. (NCT02311907)
Timeframe: Up to 1 year

,
Interventionpercentage of participants (Number)
Reduced TAXOL Dose : YesReduced CARBO Dose: Yes
A (Glutathione, Carboplatin)2.11.1
B (Placebo, Paclitaxel)1.10.0

[back to top]

Percentage of Patients With Grade 2+ and Grade 3+ Paclitaxel/Carboplatin-induced (PCI) Peripheral Neuropathy (PN) According to the Common Terminology Criteria for Adverse Events (CTCAE) Neuropathy Scale

Proportion of grade 2+ and grade 3+ chemotherapy induced peripheral neuropathy (CIPN) at any time during or at the end of the TAXOL/CBDCA based chemotherapy between GSH and placebo arms. Neuropathy scale has grades 1 through 5 (1-mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening and Grade 5 Death related to AE). (NCT02311907)
Timeframe: Up to 1 year

,
Interventionpercentage of participants (Number)
Grade 2+ CIPN: YesGrade 3+ CIPN: Yes
A (Glutathione, Carboplatin)38.35.3
B (Placebo, Paclitaxel)33.04.4

[back to top]

Rate of Pathologic Complete Response (pCR) Based on Response Evaluation Criteria in Solid Tumors Criteria

The pCR rate will first be determined as proportions and calculating its 95% confidence interval. To study the association between pCR response (yes/no) and the presence of gross residual disease, type and number of mutations, clinical lymph node status (positive/negative), tumor size (< 2 cm/>= 2 cm) based on p53, logistic regression analysis will be used, controlling for cancer treatment and disease stage and other covariates if numbers allow. (NCT02315196)
Timeframe: Disease was evaluated at baseline to after four cycles every 28 days and then after twelve weeks of treatment after surgery (up to 28 weeks from baseline).

InterventionParticipants (Count of Participants)
Treatment (Doxil, Carboplatin, Surgery, Paclitaxel)16

[back to top]

Event Free Survival Rate

measure the event free survival rate for the patients at 18 months: patients that without tumor relapse or metastasis (NCT02319486)
Timeframe: 18 months

Interventionparticipants (Number)
CEV With/Without Carboplatin- Stage 27
CEV With/Without Carboplatin - Stage 34

[back to top]

Progression Free Survival

PFS is defined as time from enrollment to time of progression or death. Disease progression (PD) may be determined objectively per RECIST 1.1 (Response Evaluation Criteria in Solid Tumors, where PD is defined as a 20% increase in the sum of longest diameters of target lesions, a measurable increase in non-target lesion, or appearance of new lesions) or subjectively as determined by investigator (with evidence documented in the medical records). If the subject died without documented PD, date of progression will be date of death. For surviving subjects who did not have documented PD, PFS was censored at last radiologic assessment. For subjects who received subsequent anti-cancer therapy prior to documented PD, PFS was censored at last radiologic assessment prior to commencement of subsequent therapy. Subjects who experienced a PFS event following an interval equal to two or more scheduled radiologic assessments were censored at last assessment prior to first missed assessment. (NCT02328105)
Timeframe: From date of treatment start to date of progression/death, or censored as described above; assessed for approximately 3 years

Interventionmonths (Median)
Carboplatin + Abraxane7.3

[back to top]

Number of Subjects With Stable Disease or Response

Disease control is calculated for each subject indicating whether or not they achieved an overall response of stable disease or better by RECIST 1.1 (where a CR is indicated by disappearance of all target and non target lesions, a PR is indicated by >= 30% decrease in sum of longest diameter of target lesions with baseline as reference, and SD is neither sufficient shrinkage to qualify for PR nor sufficient growth, >=20%, to indicate progression). (NCT02328105)
Timeframe: 18 weeks

InterventionParticipants (Count of Participants)
Carboplatin + Abraxane9

[back to top]

Overall Survival

OS is defined as the duration of time from enrollment to the date of death from any cause. Subjects who were alive or lost to follow-up at the time of the analysis were censored at the last known date they were alive. (NCT02328105)
Timeframe: From date of treatment start to date of death, or censored as described above; assessed for approximately 3 years

Interventionmonths (Median)
Carboplatin + Abraxane30

[back to top]

Number of Participants With a Response

The primary endpoint is a binary variable determined for each patient indicating whether or not they achieved a complete response (CR) or a partial response (PR) as per RECIST 1.1 (where a CR is indicated by disappearance of all target and non target lesions and a PR is indicated by >= 30% decrease in sum of longest diameter of target lesions with baseline as reference). Because overall response is the primary endpoint for this study, best responses of CR or PR must be confirmed by a subsequent radiologic assessment. (NCT02328105)
Timeframe: Up to a planned 18 weeks

InterventionParticipants (Count of Participants)
Carboplatin + Abraxane4

[back to top]

Duration of Response

For subjects who achieve a CR or PR, response duration will be measured from the first day of the response until the day on which progressive disease (PD) or death occurred. The censoring method will be the same as that described for PFS. (NCT02328105)
Timeframe: From date of response to date of progression/death, or censored as described above; assessed for approximately 3 years.

Interventionmonths (Median)
Carboplatin + Abraxane10.8

[back to top]

Duration of Disease Control

For subjects who achieve SD or better, duration of disease control will be measured from the treatment start date until the day on which progressive disease (PD) or death occurred. The censoring method will be the same as that described for PFS. (NCT02328105)
Timeframe: From date of treatment start to date of progression, or censored as described above; assessed for approximately 3 years

Interventionmonths (Median)
Carboplatin + Abraxane7.3

[back to top]

Progression Free Survival

Defined as the time from randomization to the first objective documentation of disease progression, defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions, or death due to any cause with patients who had not progressed or died at the time of final analysis censored on the date of the last tumour assessment. (NCT02337530)
Timeframe: 3 years

Interventionmonths (Median)
Intermittent Oral Selumatinib With Pemetrexed and Platinum7.2
Continuous Oral Selumatinib With Pemetrexed and Platinum6.9
Pemetrexed and Platinum Alone4.0

[back to top]

Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 17.95
Cohort 1a8.00

[back to top]

Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionh*ng/mL (Geometric Mean)
Cohort 139370
Cohort 1a44630
Cohort 251340

[back to top]

Time to Maximum Plasma Concentration (Tmax) of AZD1775 at Steady State When Given in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 14.00
Cohort 1a3.09
Cohort 24.04

[back to top]

Number of Patients With Treatment-Emergent Adverse Events During AZD1775 Monotherapy Cycle by System Organ Class and Preferred Term

The number of patients with TEAEs during AZD1775 Monotherapy Cycle was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. (NCT02341456)
Timeframe: Up to 1 week

,,
InterventionParticipants (Number)
Patients with at least 1 TEAE in AZD1775 cycleGastrointestinal Disorders - NauseaGastrointestinal Disorders - ConstipationGastrointestinal Disorders - DiarrhoeaImmune System Disorders - Hypersensitivity
Cohort 111000
Cohort 1a11010
Cohort 221101

[back to top]

Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy

(NCT02341456)
Timeframe: PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

Interventionhours (Median)
Cohort 12.02
Cohort 1a3.95
Cohort 23.96

[back to top]

Time to Maximum Plasma Concentration (Tmax) of AZD1775 Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 14.00
Cohort 1a4.04
Cohort 24.00

[back to top]

Time to Maximum Plasma Concentration (Tmax) of IV Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 12.99
Cohort 23.03

[back to top]

Time to Last Detectable Concentration (Tlast) of Paclitaxel When Given in Combination With Oral AZD1775 and IV Carboplatin

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 12.99
Cohort 23.03

[back to top]

Area Under Plasma Concentration-time Curve From 0 to Last Measurable Conc. (AUC0-t) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 & 2)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionh*ng/mL (Geometric Mean)
Cohort 156240
Cohort 1a48700

[back to top]

Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 11.97
Cohort 1a1.08

[back to top]

Area Under the Plasma Concentration-time Curve (AUC0-t) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionh*ng/mL (Geometric Mean)
Cohort 113100
Cohort 216360

[back to top]

Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) at Steady State for AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

InterventionnM*h (Geometric Mean)
Cohort 18300
Cohort 1a7154
Cohort 214870

[back to top]

Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose Administration of AZD1775 Monotherapy

(NCT02341456)
Timeframe: PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

InterventionnM*h (Geometric Mean)
Cohort 13521
Cohort 1a3387
Cohort 25331

[back to top]

Area Under the Plasma Concentration-time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) Following Single Dose of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

InterventionnM*h (Geometric Mean)
Cohort 14191
Cohort 1a2902
Cohort 25606

[back to top]

Duration of Response

The duration of response is defined as the time in weeks from the date of first documented overall response occurrence of CR or PR, (whichever was recorded first) to the earliest date that progressive disease/death was documented. If progression or death has not been documented, a patient's DoR was censored at the date of last tumour assessment. (NCT02341456)
Timeframe: Up to 18 months

InterventionWeeks (Median)
Cohort 118.1
Cohort 1a0.00
Cohort 220.7

[back to top]

Number of Patients With an Objective Response

Objective response is defined as either a complete response or a partial response. (NCT02341456)
Timeframe: Up to 18 months

InterventionParticipants (Number)
Cohort 11
Cohort 1a1
Cohort 23

[back to top]

Best Overall Response

The number of subjects with best overall response in CR, PR, NE, SD, PD subcategory. Best overall response is calculated based on the overall visit responses from each RECIST assessment. (NCT02341456)
Timeframe: Up to 18 months

,,
InterventionParticipants (Number)
Partial ResponseNot EvaluableStable DiseaseProgressive DiseaseComplete Response
Cohort 111220
Cohort 1a12210
Cohort 231200

[back to top]

Peak Plasma Concentration (Cmax) of AZD1775 at Steady State When Given in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

InterventionnM (Geometric Mean)
Cohort 11271
Cohort 1a1129
Cohort 22289

[back to top]

Peak Plasma Concentration (Cmax) of AZD1775 Following Oral Dose of AZD1775 in Combination With IV Infusion of Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

InterventionnM (Geometric Mean)
Cohort 1705.4
Cohort 1a654.8
Cohort 21133

[back to top]

Number of Patients With Clinically Important Abnormalities in Clinical Chemistry by Preferred Term

The number of patients with clinically important changes in clinical chemistry TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. (NCT02341456)
Timeframe: Up to 21 days (1 Cycle)

,,
InterventionParticipants (Number)
Aspartate aminotransferase increasedAlanine aminotransferase increasedBlood alkaline phosphatase increasedBlood lactate dehydrogenase increasedC-reactive protein increasedHypoalbuminemiaHypokalemiaHypophosphatemiaDehydrationHyperglycaemiaHypocalcaemiaHyponatraemiaHypercalcaemiaHypercholsterolaemiaHypoglycaemiaHypomagnesaemiaAzotemiaHepatic function abnormal
Cohort 1001112111201001011
Cohort 1a210000100000000000
Cohort 2100002221011110100

[back to top]

Number of Patients With Clinically Important Abnormalities in Vital Signs by Preferred Term

The number of patients with clinically important changes in vital sign TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. (NCT02341456)
Timeframe: Up to 21 days (1 Cycle)

,,
InterventionParticipants (Number)
PyrexiaHypotension
Cohort 132
Cohort 1a10
Cohort 241

[back to top]

Number of Patients With Clinically Important Changes in Haematology and Coagulation TEAEs by System Organ Class and Preferred Term

The number of patients with clinically important changes in haematology and coagulation TEAEs was analyzed in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. (NCT02341456)
Timeframe: Up to 21 days (1 Cycle)

,,
InterventionParticipants (Number)
Blood & Lymphatic System Disorders (BLSD) AnaemiaBLSD - NeutropeniaBLSD - ThrombocytopeniaBLSD - Febrile NeutropeniaInvestigations - WBC Count DecreasedInvestigations - Neutrophil Count DecreasedInvestigations - Platelet Count DecreasedInvestigations - Haematocrit DecreasedInvestigations - Monocyte Count Decreased
Cohort 1631153411
Cohort 1a401034300
Cohort 2522253300

[back to top]

Number of Patients With Treatment-Emergent Adverse Events

The number of patients with treatment-emergent adverse events was analyzed on the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. (NCT02341456)
Timeframe: Up to 21 days (1 Cycle)

,,
InterventionParticipants (Number)
Patients with ≥ 1 Adverse Event (AE)Patients with ≥ 1 Treatment-Emergent AE (TEAE)Patients with TEAE Related to TreatmentPatients with Serious TEAEPatients with Severe TEAEPatients with TEAE with AZD1775 discontinuedPatients with TEAE with paclitaxel discontinuedPatients with TEAE with carboplatin discontinuedPatients with TEAE and fatal outcomePatients with Dose-Limiting Toxicity
Cohort 17663611011
Cohort 1a664040NA001
Cohort 26664622212

[back to top]

Time to Peak Plasma Concentration of Platinum (Tmax) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 11.02
Cohort 1a1.02
Cohort 21.02

[back to top]

Number of Treatment-Emergent Adverse Events (TEAE)

The number of treatment-emergent adverse events was counted in the safety analysis set which was comprised of all patients who received at least one dose of the investigational drug. (NCT02341456)
Timeframe: Up to 21 days (1 Cycle)

,,
InterventionTEAE (Number)
Number of Adverse Events (AEs)Number of TEAEsNumber of TEAEs Related to Study TreatmentNumber of Serious TEAEsNumber of Severe TEAEsNumber of TEAEs with AZD1775 discontinuedNumber of TEAEs with paclitaxel discontinuedNumber of TEAEs with carboplatin discontinuedNumber of TEAEs with fatal outcomeNumber of Dose-Limiting Toxicities (DLT)Number of TEAEs with DLT
Cohort 1370362262988310111
Cohort 1a202182950230NA0011
Cohort 23823812639101333222

[back to top]

Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

InterventionnM (Geometric Mean)
Cohort 1444.6
Cohort 1a378.2
Cohort 2805.9

[back to top]

Plasma Concentration of AZD1775 8 Hours After Single Dose Administration (C8h) of AZD1775 Monotherapy

(NCT02341456)
Timeframe: PK Samples will be collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

InterventionnM (Geometric Mean)
Cohort 1370.1
Cohort 1a343.5
Cohort 2612

[back to top]

Number of Patients With Clinical Benefit

Clinical benefit is defined as achieving complete response, partial response, or stable disease. (NCT02341456)
Timeframe: Up to 18 months

InterventionParticipants (Number)
Cohort 13
Cohort 1a3
Cohort 25

[back to top]

Plasma Concentration of Paclitaxel at the End of Infusion (Ceoi) When Given Combination With Oral AZD1775 and IV Carboplatin.

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionng/mL (Geometric Mean)
Cohort 14791
Cohort 25361

[back to top]

Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionng/mL (Geometric Mean)
Cohort 113300
Cohort 1a18550
Cohort 217500

[back to top]

Plasma Concentration of Platinum at the End of Infusion (Ceoi) When Given as a 2 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionng/mL (Geometric Mean)
Cohort 115960
Cohort 1a12200

[back to top]

Time to Last Detectable Concentration of Platinum (Tlast) When Given as a 1 Hour Infusion in Combination With Oral AZD1775 and IV Paclitaxel.

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionhours (Median)
Cohort 17.98
Cohort 1a7.28
Cohort 28.00

[back to top]

Peak Plasma Concentration (Cmax) of AZD1775 Following Single Dose Administration of AZD1775 Monotherapy

(NCT02341456)
Timeframe: PK Samples collected in all treatment groups on Cycle 0 Day 1, Cycle 1 Day 1, and Cycle 1 Day 3 before the first (morning) dose of AZD1775 (predose) and at 1, 2, 4, 6, and 8 hours postdose

InterventionnM (Geometric Mean)
Cohort 1689.1
Cohort 1a649.2
Cohort 21066

[back to top]

Peak Plasma Concentration (Cmax) of Paclitaxel Following Single IV Infusion in Combination With Single Dose Oral AZD1775 and IV Carboplatin

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionng/mL (Geometric Mean)
Cohort 14848
Cohort 25361

[back to top]

Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 1 Hour in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionng/mL (Geometric Mean)
Cohort 113300
Cohort 1a18550
Cohort 217500

[back to top]

Peak Plasma Concentration (Cmax) of Platinum Following Single IV Infusion of Carboplatin Over 2 Hours in Combination With Single Oral Dose AZD1775 Alone (Cohort 1a) or With IV Paclitaxel (Cohorts 1 and 2)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

Interventionng/mL (Geometric Mean)
Cohort 115960
Cohort 1a13200

[back to top]

Percentage of Patients With an Objective Response

Objective response is defined as either a complete response or a partial response. (NCT02341456)
Timeframe: Up to 18 months

InterventionPercentage (Number)
Cohort 116.7
Cohort 1a16.7
Cohort 250

[back to top]

Percentage of Patients With Clinical Benefit

Clinical benefit is defined as achieving complete response, partial response, or stable disease. (NCT02341456)
Timeframe: Up to 18 months

InterventionPercentage (Number)
Cohort 150
Cohort 1a50
Cohort 283.3

[back to top]

Plasma Concentration of AZD1775 8 Hours After Administration (C8h) at Steady State in Combination With IV Paclitaxel and Carboplatin (Cohorts 1 and 2) or Carboplatin Alone (Cohort 1a)

(NCT02341456)
Timeframe: AZ1775:C0D1, C1D1, & C1D3 before AZD1775 dose and at 1,2,4,6&8 hrs postdose. Paclitaxel:C1D1 before paclitaxel infusion & at 1.5,3,4,6&8 hrs after start of infusion Carboplatin:C1D1 before carboplatin infusion &at 1,2,4,6&8 hrs after start of infusion

InterventionnM (Geometric Mean)
Cohort 1982
Cohort 1a774.6
Cohort 21700

[back to top]

Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)28.7
Cetuximab + Chemotherapy (Control)43.9

[back to top]

Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)23.3
Cetuximab + Chemotherapy (Control)36.1

[back to top]

Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)23.5
Cetuximab + Chemotherapy (Control)15.1

[back to top]

Pembro Combo vs Control: Overall Survival (OS) in All Participants

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and control arm. Per protocol, OS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)13.0
Cetuximab + Chemotherapy (Control)10.7

[back to top]

Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)17.2
Cetuximab + Chemotherapy (Control)13.6

[back to top]

Pembro Combo vs Control: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in All Participants

ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro combo arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)35.6
Cetuximab + Chemotherapy (Control)36.3

[back to top]

Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)23.9
Cetuximab + Chemotherapy (Control)14.0

[back to top]

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)44.7
Cetuximab + Chemotherapy (Control)44.9

[back to top]

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)44.9
Cetuximab + Chemotherapy (Control)43.3

[back to top]

Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)36.4
Cetuximab + Chemotherapy (Control)35.7

[back to top]

Number of Participants Who Discontinued Study Drug Due to an AE

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued study drug due to an AE was reported for each treatment arm. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionParticipants (Count of Participants)
Pembrolizumab Monotherapy (Pembro Mono)36
Pembrolizumab + Chemotherapy (Pembro Combo)90
Cetuximab + Chemotherapy (Control)79

[back to top]

Number of Participants Experiencing an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionParticipants (Count of Participants)
Pembrolizumab Monotherapy (Pembro Mono)290
Pembrolizumab + Chemotherapy (Pembro Combo)271
Cetuximab + Chemotherapy (Control)286

[back to top]

Pembro Combo vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, ORR was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)42.9
Cetuximab + Chemotherapy (Control)38.2

[back to top]

Pembro Combo vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)49.4
Cetuximab + Chemotherapy (Control)47.2

[back to top]

Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as Combined Positive Score ≥20 (hereafter referred to as CPS ≥20). Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)5.8
Cetuximab + Chemotherapy (Control)5.3

[back to top]

Pembro Combo vs Control: PFS Per RECIST 1.1 by BICR in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by immunohistochemistry (IHC) as Combined Positive Score ≥1 (hereafter referred to as CPS ≥1). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)5.1
Cetuximab + Chemotherapy (Control)5.0

[back to top]

Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥1

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)13.6
Cetuximab + Chemotherapy (Control)10.4

[back to top]

Pembro Combo vs Control: OS in Participants With PD-L1 CPS ≥20

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)14.7
Cetuximab + Chemotherapy (Control)11.0

[back to top]

Pembro Combo vs Control: Change From Baseline to Week 15 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared between all participants of the pembro combo arm and the control arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Baseline, Week 15

InterventionScore on a Scale (Least Squares Mean)
Pembrolizumab + Chemotherapy (Pembro Combo)1.17
Cetuximab + Chemotherapy (Control)0.77

[back to top]

Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)20.6
Cetuximab + Chemotherapy (Control)13.6

[back to top]

Pembro Mono vs Control: OS in All Participants

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and control arm. Per protocol, OS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)11.5
Cetuximab + Chemotherapy (Control)10.7

[back to top]

Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥20

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, OS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)14.8
Cetuximab + Chemotherapy (Control)10.7

[back to top]

Pembro Combo vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro combo arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between CPS ≥1 participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy (Pembro Combo)19.7
Cetuximab + Chemotherapy (Control)12.5

[back to top]

Pembro Mono vs Control: Percentage of Participants With PFS at 12 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 12 months is reported here out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 12 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)17.6
Cetuximab + Chemotherapy (Control)15.0

[back to top]

Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)26.2
Cetuximab + Chemotherapy (Control)45.7

[back to top]

Pembro Combo vs Control: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in All Participants

"PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro combo arm was compared to the control arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for all participants in the pembro combo arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)4.9
Cetuximab + Chemotherapy (Control)5.2

[back to top]

Pembro Combo vs Control: Time to Deterioration (TTD) in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score (Kaplan-Meier Method)

"EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in GHS/QoL combined score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record." (NCT02358031)
Timeframe: Baseline up to approximately 12 months

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)NA
Cetuximab + Chemotherapy (Control)NA

[back to top]

Pembro Combo vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score (Kaplan-Meier Method)

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)NA
Cetuximab + Chemotherapy (Control)NA

[back to top]

Pembro Mono vs Control: OS in Participants With PD-L1 CPS ≥1

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)12.3
Cetuximab + Chemotherapy (Control)10.3

[back to top]

Pembro Combo vs Control: TTD in the EORTC QLQ- Head and Neck Module 35 (H&N35) Pain Score (Kaplan-Meier Method)

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared between all participants of pembro combo arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro mono arm and control arm and is presented later in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

InterventionMonths (Median)
Pembrolizumab + Chemotherapy (Pembro Combo)NA
Cetuximab + Chemotherapy (Control)NA

[back to top]

Pembro Mono vs Control: TTD in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score

"EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD in GHS/QoL defined as the time from baseline to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score, with confirmation. Per protocol, TTD in GHS/QoL combined score was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in GHS/QoL combined score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Baseline up to approximately 12 months

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)NA
Cetuximab + Chemotherapy (Control)NA

[back to top]

Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Swallowing Score

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Swallowing scale (Items 35-38) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Swallowing Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Swallowing Score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)NA
Cetuximab + Chemotherapy (Control)NA

[back to top]

Pembro Mono vs Control: TTD in the EORTC QLQ- H&N35 Pain Score

EORTC QLQ-H&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multi-item scales that assess pain, swallowing, senses, speech, social eating, social contact and sexuality. Participant responses to the Pain scale (Items 31-34) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. TTD in EORTC QLQ-H&N35 Pain Score defined as the time from baseline to the first onset of a ≥10 point decrease from baseline, with confirmation. Per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared between all participants of pembro mono arm and control arm as a pre-specified secondary analysis. Also per protocol, TTD in EORTC QLQ-H&N35 Pain Score was compared separately between all participants of pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Baseline up to approximately 12 months

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)NA
Cetuximab + Chemotherapy (Control)NA

[back to top]

Pembro Mono vs Control: Change From Baseline to Week 15 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared between all participants of the pembro mono arm and the control arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 15 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Baseline, Week 15

InterventionScore on a Scale (Least Squares Mean)
Pembrolizumab Monotherapy (Pembro Mono)0.85
Cetuximab + Chemotherapy (Control)0.60

[back to top]

Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥1. Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)3.2
Cetuximab + Chemotherapy (Control)5.0

[back to top]

Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in All Participants

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and control arm. Per protocol, PFS was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)2.3
Cetuximab + Chemotherapy (Control)5.2

[back to top]

Pembro Mono vs Control: Percentage of Participants With PFS at 6 Months Per RECIST 1.1 by BICR Among Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants with PFS (PFS rate) at 6 months is reported here out of all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥20 in the pembro mono arm and control arm. Per protocol, the percentage of participants with PFS at 6 months was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)33.0
Cetuximab + Chemotherapy (Control)46.6

[back to top]

Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in All Participants

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro mono arm and control arm. Per protocol, ORR was compared separately between all participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)16.9
Cetuximab + Chemotherapy (Control)36.0

[back to top]

Pembro Mono vs Control: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1

ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the control arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants with PD-L1 biomarker positive expression defined by IHC as CPS ≥1 in the pembro mono arm and control arm. Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and control arm and is presented earlier in the record. (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionPercentage of Participants (Number)
Pembrolizumab Monotherapy (Pembro Mono)19.1
Cetuximab + Chemotherapy (Control)34.9

[back to top]

Pembro Mono vs Control: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥20

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.~Per protocol, PFS in the pembro mono arm was compared to the control arm as a pre-specified primary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and control arm with PD-L1 biomarker positive expression defined by IHC as CPS ≥20. Per protocol, PFS was compared separately between CPS ≥20 participants of the pembro combo arm and control arm and is presented earlier in the record." (NCT02358031)
Timeframe: Up to approximately 47 months (through Final Analysis cut-off date of 25-Feb-2019)

InterventionMonths (Median)
Pembrolizumab Monotherapy (Pembro Mono)3.4
Cetuximab + Chemotherapy (Control)5.3

[back to top]

Serum Concentration of Bevacizumab up to 1 Year

(NCT02364999)
Timeframe: Pre-dose from Cycle 1 to Cycle 17, 2.5 hours post-dose in Cycle 1, and 1.5 hours post-dose in Cycle 5

,
Interventionng/mL (Mean)
Pre-dose in Cycle 12.5 hours post-dose in Cycle 1Pre-dose in Cycle 2Pre-dose in Cycle 3Pre-dose in Cycle 4Pre-dose in Cycle 51.5 hours post-dose in Cycle 5Pre-dose in Cycle 6Pre-dose in Cycle 7Pre-dose in Cycle 8Pre-dose in Cycle 9Pre-dose in Cycle 10Pre-dose in Cycle 11Pre-dose in Cycle 12Pre-dose in Cycle 13Pre-dose in Cycle 14Pre-dose in Cycle 15Pre-dose in Cycle 16Pre-dose in Cycle 17
Bevacizumab-EU116.4302200589308335099750110000377200116700122100126400140900135900135600136300139700136200134000128600127500
PF-0643953568.082800005435081090100900105300360700112000117300123600127200125700129500135200130900128000134000137000134800

[back to top]

Number of Participants With Neutralizing Antibody (NAb)

Only samples that were confirmed positive for ADA were further tested for NAb. The NAb analysis was conducted using a single validated quasi-quantitative enzyme-linked immunosorbent assay (ELISA) that utilized PF-06439535 as a reagent. Samples with NAb titer >=1.70 were considered positive. (NCT02364999)
Timeframe: 55 weeks

,
InterventionParticipants (Count of Participants)
Cycle 1 pre-doseOverall (post-treatment)
Bevacizumab-EU03
PF-0643953510

[back to top]

Number of Participants With Treatment-Emergent Adverse Events

AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. (NCT02364999)
Timeframe: 55 weeks

,
InterventionParticipants (Count of Participants)
All-causality AEAll-causality SAEBevacizumab-related AEBevacizumab-related SAEGrade 1 all-causality AEGrade 2 all-causality AEGrade 3 all-causality AEGrade 4 all-causality AEGrade 5 all-causality AE
Bevacizumab-EU3478019917411341044424
PF-064395353448119023321411252521

[back to top]

Number of Participants With Anti-Drug Antibody (ADA)

ADA assay was performed using a sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) method, which used biotinylated- and ruthenium-labeled PF-06439535 as reagents. Samples with ADA titer greater than or equal to (>=) 2.29 were considered positive. (NCT02364999)
Timeframe: 55 weeks

,
InterventionParticipants (Count of Participants)
Cycle 1 pre-doseOverall (post-treatment)
Bevacizumab-EU35
PF-0643953515

[back to top]

Progression Free Survival Rate at 55 Weeks

This outcome measure refers to the possibility of being progression free at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method. (NCT02364999)
Timeframe: 55 weeks

Interventionpercentage of participants (Number)
PF-0643953532.3
Bevacizumab-EU30.5

[back to top]

Objective Response Rate (ORR) by Week 19

ORR refers to percentage of participants who achieved complete response (CR) or partial response (PR) by Week 19 of the study in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 which was subsequently confirmed by Week 25. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved PR if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits. (NCT02364999)
Timeframe: 25 weeks

Interventionpercentage of participants (Number)
PF-0643953545.3
Bevacizumab-EU44.6

[back to top]

Duration of Response (DOR)

DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of PD or to death due to any cause in the absence of documented PD. DOR was based on the Brookmeyer and Crowley method. (NCT02364999)
Timeframe: 55 weeks

Interventionweeks (Median)
PF-0643953536.3
Bevacizumab-EU28.7

[back to top]

Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)

Laboratory evaluation included hematology (hemoglobin, white blood cells, platelets and absolute neutrophil count), blood chemistry (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, serum or plasma creatinine, sodium, potassium, total calcium, magnesium, blood urea nitrogen or urea, and albumin ), coagulation (international normalized ratio for prothrombin time and activated partial thromboplastin time) and urinalysis (dipstick followed by a quantitative urine protein analysis for results of 2+ or greater). (NCT02364999)
Timeframe: 55 weeks

InterventionParticipants (Count of Participants)
PF-06439535303
Bevacizumab-EU304

[back to top]

Survival Rate at 55 Weeks

This outcome measure refers to the possibility of being alive at 55 weeks since start of study treatment, estimated from the Kaplan-Meier curve using the product-limit method. (NCT02364999)
Timeframe: 55 weeks

Interventionpercentage of participants (Number)
PF-0643953565.8
Bevacizumab-EU64.1

[back to top]

OS in Arm A Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population

(NCT02366143)
Timeframe: Baseline until death (up approximately 53 months)

,
InterventionMonths (Median)
Teff-high WT PopulationTeff-high PopulationITT Population
Arm A (Atezolizumab+Paclitaxel+Carboplatin)21.321.019.0
Arm C (Bevacizumab+Paclitaxel+Carboplatin)16.316.715.0

[back to top]

OS in Arm A Versus Arm C by PD-L1 Subgroup

OS in Arm A Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population) (NCT02366143)
Timeframe: Baseline until death (up approximately 53 months)

,
InterventionMonths (Median)
TC2/3 or IC2/3 PopulationTC1/2/3 or IC1/2/3 Population
Arm A (Atezolizumab+Paclitaxel+Carboplatin)26.124.4
Arm C (Bevacizumab+Paclitaxel+Carboplatin)17.016.0

[back to top]

OS in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population

(NCT02366143)
Timeframe: Baseline until death (up approximately 53 months)

,
InterventionMonths (Median)
Teff High-WT PopulationITT-WT Population
Arm A (Atezolizumab+Paclitaxel+Carboplatin)21.319.0
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)25.819.5

[back to top]

Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Arm A and Arm B

(NCT02366143)
Timeframe: Day 21 of Cycles 1, 2 3, and 7 (Cycle length=21 days)

,
Interventionmcg/mL (Mean)
Cycle 1 Day 21Cycle 2 Day 21Cycle 3 Day 21Cycle 7 Day 21
Arm A (Atezolizumab+Paclitaxel+Carboplatin)76.4119146219
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)80.8130160220

[back to top]

Maximum Observed Serum Concentration (Cmax) of Atezolizumab in Arm A and Arm B

The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes. (NCT02366143)
Timeframe: Day 1 of Cycle 1 and 3 (Cycle length=21 days)

,
Interventionmcg/mL (Mean)
Cycle 1 Day 1Cycle 3 Day 1
Arm A (Atezolizumab+Paclitaxel+Carboplatin)410498
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)414540

[back to top]

Duration of Response (DOR), as Determined By Investigator in Arm B Versus Arm C

DOR, as determined by investigator according to RECIST v1.1 in Arm B versus Arm C in the Teff high-WT population and the ITT-WT population. (NCT02366143)
Timeframe: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

,
InterventionMonths (Median)
Teff high-WT PopulationITT-WT Population
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)11.29.0
Arm C (Bevacizumab+Paclitaxel+Carboplatin)5.75.7

[back to top]

Cmin of Bevacizumab in Arm B and Arm C

(NCT02366143)
Timeframe: Cycle 1 Day 1 and Cycle 2 Day 21 (Cycle length=21 days)

,
Interventionmcg/mL (Mean)
Cycle 1 Day 1Cycle 2 Day 21
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)NA98.0
Arm C (Bevacizumab+Paclitaxel+Carboplatin)NA90.4

[back to top]

Cmax of Bevacizumab in Arm B and Arm C

(NCT02366143)
Timeframe: Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length=21 days)

,
Interventionmcg/mL (Mean)
Cycle 1 Day 1Cycle 3 Day 1
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)329413
Arm C (Bevacizumab+Paclitaxel+Carboplatin)323430

[back to top]

Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

(NCT02366143)
Timeframe: Baseline up to approximately 29 months

InterventionPercentage of Participants (Number)
Arm A (Atezolizumab+Paclitaxel+Carboplatin)4.6
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)2.9

[back to top]

Percentage of Participants With Adverse Events

Percentage of participants with at least one adverse event. (NCT02366143)
Timeframe: Baseline up to data cutoff date 7 December 2020 (up to approximately 68 months)

InterventionPercentage (Number)
Arm C (Bevacizumab+Paclitaxel+Carboplatin)99.0
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)98.2
Arm A (Atezolizumab+Paclitaxel+Carboplatin)97.8

[back to top]

Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population

Overall Survival (OS) in Arm B Versus Arm C in ITT-WT Population (NCT02366143)
Timeframe: Baseline until death until data cut-off on 22 January 2018 (up to approximately 34 months)

InterventionMonths (Median)
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)19.2
Arm C (Bevacizumab+Paclitaxel+Carboplatin)14.7

[back to top]

Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population

Overall Survival (OS) in Arm A Versus Arm C in ITT-WT Population (NCT02366143)
Timeframe: Baseline until death (up approximately 53 months)

InterventionMonths (Median)
Arm A (Atezolizumab+Paclitaxel+Carboplatin)19.0
Arm C (Bevacizumab+Paclitaxel+Carboplatin)14.7

[back to top]

OS in Arm B Versus Arm C in Teff High-WT Population, Teff High Population, and ITT Population

(NCT02366143)
Timeframe: Baseline until death (up to approximately 34 months)

,
InterventionMonths (Median)
Teff High-WT PopulationTeff High PopulationITT Population
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)25.025.219.8
Arm C (Bevacizumab+Paclitaxel+Carboplatin)16.716.714.9

[back to top]

TTD in Patient-Reported Lung Cancer Symptoms as Determined by EORTC Quality-of-Life Questionnaire-Core Lung Cancer Module 13 (QLQ-LC13) Score

QLQ-LC13 Quality-of-Life Questionnaire Lung Cancer Module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998). (NCT02366143)
Timeframe: Baseline up to approximately 29 months

,,
InterventionMonths (Median)
Cough in Teff-high WT PopulationDyspnea in Teff-high WT PopulationChest Pain in Teff-high WT PopulationArm and/or Shoulder Pain in Teff-high WTCough in ITT-WT PopulationDyspnea in ITT-WT PopulationArm and/or Shoulder Pain in ITT-WTPain in Chest in ITT-WT Population
Arm A (Atezolizumab+Paclitaxel+Carboplatin)NANANANANA21.9NANA
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)NANA22.219.5NANA19.5NA
Arm C (Bevacizumab+Paclitaxel+Carboplatin)NANA18.4NANANANANA

[back to top]

Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms Determined by European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Score

EORTC QLQ-C30 is a validated & reliable self-report measure (Aaronson et al.1993;Fitzsimmons et al.1999) that consists of 30 questions that assess 5 aspects of patient functioning (physical,emotional,role, cognitive,and social), 3 symptom scales (fatigue,nausea & vomiting, pain),global health/quality of life,and six single items (dyspnea,insomnia, appetite loss,constipation,diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life);however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al.1998). (NCT02366143)
Timeframe: Baseline up to approximately 29 months

,,
InterventionMonths (Median)
Dyspnea in Teff-high WT PopulationDyspnea in ITT-WT Population
Arm A (Atezolizumab+Paclitaxel+Carboplatin)NANA
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)NANA
Arm C (Bevacizumab+Paclitaxel+Carboplatin)NANA

[back to top]

Progression Free Survival (PFS), as Determined by the Investigator in Arm B Versus Arm C in the Teff-high WT Population and ITT-WT Population

Progression Free Survival (PFS), as Determined by the Investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population. (NCT02366143)
Timeframe: Baseline until disease progression or death, whichever occurs first until data cut-off on 15 September 2017 (up to approximately 29 months)

,
InterventionMonths (Median)
Teff-high WT PopulationITT-WT Population
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)11.38.3
Arm C (Bevacizumab+Paclitaxel+Carboplatin)6.86.8

[back to top]

Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C

(NCT02366143)
Timeframe: Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days)

,
Interventionng/mL (Mean)
Cy1D1 Pre-doseCy1D1 Before End of InfusionCy1D1 After InfusionCy2D21Cy3D1 Before End Of InfusionCy3D1 After Infusion
Arm A (Atezolizumab+Paclitaxel+Carboplatin)NA48502300NA58101800
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)NA64402490NA78102990

[back to top]

Plasma Concentrations for Paclitaxel in Arm A, Arm B, and Arm C

(NCT02366143)
Timeframe: Predose (same day of treatment administration), 5-10 minutes before end of paclitaxel infusion, 1 h after paclitaxel infusion (infusion duration=3 h) on D1 of Cy1,3 (Cycle length=21 days)

Interventionng/mL (Mean)
Cy1D1 Pre-doseCy1D1 Before End of InfusionCy1D1 After InfusionCy3D1 Before End Of InfusionCy3D1 After Infusion
Arm C (Bevacizumab+Paclitaxel+Carboplatin)NA5560198078101930

[back to top]

Plasma Concentrations for Carboplatin in Arm A, Arm B, and Arm C

(NCT02366143)
Timeframe: Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 h after carboplatin infusion (infusion duration=15 to 30 minutes) on D1 of Cy1,3 (Cycle length=21 days)

,,
Interventionng/mL (Mean)
Cy1D1 Pre-doseCy1D1 Before End of InfusionCy1D1 After InfusionCy2D21Cy3D1 Before End of InfusionCy3D1 After Infusion
Arm A (Atezolizumab+Paclitaxel+Carboplatin)NA18300117001762090011700
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)NA18300139001901870012200
Arm C (Bevacizumab+Paclitaxel+Carboplatin)NA17200101001432060010400

[back to top]

PFS, as Determined by the Investigator in Arm B Versus Arm C in Teff High Population and ITT Population

PFS, as determined by the investigator according to RECIST v1.1, in Arm B versus C in the Teff high population and ITT population. (NCT02366143)
Timeframe: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

,
InterventionMonths (Median)
Teff-high PopulationITT Population
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)11.38.3
Arm C (Bevacizumab+Paclitaxel+Carboplatin)6.86.8

[back to top]

PFS, as Determined by the Investigator in Arm B Versus Arm C by PD-L1 Subgroup

PFS as Determined by the Investigator according to RECIST v1.1, in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population) (NCT02366143)
Timeframe: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

,
InterventionMonths (Median)
TC2/3 or IC2/3 SubgroupTC1/2/3 or IC1/2/3 Subgroup
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)11.111.0
Arm C (Bevacizumab+Paclitaxel+Carboplatin)6.86.8

[back to top]

PFS, as Determined by the Investigator in Arm A Versus Arm B in Teff High-WT Population and ITT-WT Population

PFS, as determined by the investigator according to RECIST v1.1, in Arm A versus B in the Teff high-WT population and ITT-WT population. (NCT02366143)
Timeframe: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

,
InterventionMonths (Median)
Teff-high WTITT-WT
Arm A (Atezolizumab+Paclitaxel+Carboplatin)6.36.3
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)11.38.3

[back to top]

PFS, as Determined by the Independent Review Facility (IRF) in Arm B Versus Arm C in Teff-High-WT Population and ITT-WT Population

PFS, as determined by the independent review facility (IRF) Using RECIST v1.1 in Arm B versus Arm C in the T-effector (Teff)-high wild type (WT) population and the intent-to-treat (ITT)-WT population. (NCT02366143)
Timeframe: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

,
InterventionMonths (Median)
Teff-high WT PopulationITT-WT Population
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)10.78.5
Arm C (Bevacizumab+Paclitaxel+Carboplatin)7.07.0

[back to top]

Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator in the Teff-High-WT Population and ITT-WT Population

Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator using RECIST v1.1 in the Teff-High-WT population and ITT-WT population. (NCT02366143)
Timeframe: Baseline until disease progression or death, whichever occurs first (up to approximately 29 months)

,,
InterventionPercentage (Number)
Teff-high WT PopulationITT-WT Population
Arm A (Atezolizumab+Paclitaxel+Carboplatin)54.049.3
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)69.363.5
Arm C (Bevacizumab+Paclitaxel+Carboplatin)53.548.0

[back to top]

OS Rates at Years 1 and 2 in Arm B Versus Arm C

OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population. (NCT02366143)
Timeframe: Baseline to 2 years or death, whichever occurs first.

,
InterventionPercentage (Number)
1-Year Teff-high WT Population1-Year ITT-WT Population2-Year Teff-high WT Population2-Year ITT-WT Population
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)68.6367.3252.0343.42
Arm C (Bevacizumab+Paclitaxel+Carboplatin)58.7460.6341.7033.71

[back to top]

OS Rates at Years 1 and 2 in Arm A Versus Arm C

OS at 1- and 2-year landmark timepoints in Teff-high WT population and ITT-WT population. (NCT02366143)
Timeframe: Baseline to 2 years or death, whichever occurs first.

,
InterventionPercentage (Number)
1-Year Teff-high WT Population2-Year Teff-high WT Population1-Year ITT-WT Population2-Year ITT-WT Population
Arm A (Atezolizumab+Paclitaxel+Carboplatin)67.4846.0164.0641.45
Arm C (Bevacizumab+Paclitaxel+Carboplatin)56.9238.7459.8931.79

[back to top]

OS in Arm B Versus Arm C by PD-L1 Subgroup

OS in Arm B Versus Arm C by PD-L1 Subgroup: TC2/3 or 1C2/3 and TC1/2/3 or IC1/2/3 (ITT-WT Population) (NCT02366143)
Timeframe: Baseline until death (up to approximately 34 months)

,
InterventionMonths (Median)
TC 2/3 or IC2/3 PopulationTC1/2/3 or IC1/2/3 Population
Arm B (Atezolizumab+Bevacizumab+Paclitaxel + Carboplatin)22.222.5
Arm C (Bevacizumab+Paclitaxel+Carboplatin)16.716.4

[back to top]

OS as Determined by the Investigator Using Recist v1.1 in the ITT Population

OS is defined as the time between the date of randomization and date of death from any cause in the ITT population. (NCT02367781)
Timeframe: Up to approximately 41 months after first subject enrolled

InterventionMonths (Median)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)17.0
Arm B (Nab-Paclitaxel+Carboplatin)13.5

[back to top]

Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1 in ITT-WT Population, ITT Population, and PD-L1 Expression Population and PD-L1 Expression WT Population

DOR,defined for participants with objective response (OR) as time from 1st documented OR to documented disease progression as determined by investigator using RECIST v1.1,or death from any cause,whichever occurs 1st.ITT defined as all randomized participants,regardless of receipt of assigned treatment.ITT-WT defined as ITT population excluding participants with activating EGFR mutation or ALK translocation.PD-L1 expression population is defined as one of following:PD-L1 IHC TC1/2/3 or IC1/2/3 population,defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue;PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue;PD-L1 IHC TC3 or IC3 population,defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue.PD-L1 expression WT is defined as PD-L1 expression population excluding participants with activating EGFR mutation or ALK translocation. (NCT02367781)
Timeframe: Up to approximately 35 months after first subject enrolled

,
InterventionMonths (Median)
ITT PopulationITT-WT PopulationTC1/2/3 or IC1/2/3 ITT PopulationTC1/2/3 or IC1/2/3 ITT WT Population
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)6.26.77.27.2
Arm B (Nab-Paclitaxel+Carboplatin)5.45.45.05.0

[back to top]

Event Free Rate (%) at Year 1 and 2 in ITT-WT Population and ITT Population

The OS rate at the 1- and 2-year landmark time points after randomization. (NCT02367781)
Timeframe: Up to 41 months after first patient enrolled, years 1 and 2 reported

,
InterventionPercentage of participants (Number)
Event Free Rate (%) at Year 1 ITT WTEvent Free Rate (%) at Year 2 ITT WTEvent Free Rate (%) at Year 1 ITTEvent Free Rate (%) at Year 2 ITT
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)62.0240.4361.6539.73
Arm B (Nab-Paclitaxel+Carboplatin)54.5632.3654.4732.21

[back to top]

Event Free Rate (%) at Year 1 and 2 in PD-L1 Expression Population and PD-L1 Expression WT Population

The OS rate at the 1- and 2-year landmark time points after randomization in the PD-L1 Expression Population and PD-L1 Expression WT Population. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. The PD-L1 expression WT population is defined as the PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation. (NCT02367781)
Timeframe: Up to 35 months after first patient enrolled, years 1 and 2 reported

,
InterventionPercentage of participants (Number)
Event Free Rate (%) at Year 1 TC1/2/3 or IC1/2/3 ITTEvent Free Rate (%) at Year 2 TC1/2/3 or IC1/2/3 ITTEvent Free Rate (%) at Year 1 TC1/2/3 or IC1/2/3 ITT WTEvent Free Rate (%) at Year 2 TC1/2/3 or IC1/2/3 ITT WT
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)68.5644.6368.8444.02
Arm B (Nab-Paclitaxel+Carboplatin)61.8635.9862.5135.33

[back to top]

Maximum Observed Serum Concentration (Cmax) of Atezolizumab for Patients in Atezolizumab+Carboplatin+Nab-Paclitaxel Arm

Predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes. (NCT02367781)
Timeframe: Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days)

Interventionmcg/mL (Mean)
Cycle 1 Day 1Cycle 3 Day 1
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)392454

[back to top]

Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT-WT Population

ORR (confirmation not required) is defined as the proportion of participants with an objective response, either CR or PR, with the use of RECIST v1.1, as determined by the investigator in the ITT-WT population. (NCT02367781)
Timeframe: Up to approximately 41 months after first subject enrolled

InterventionPercentage of participants (Number)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)60.2
Arm B (Nab-Paclitaxel+Carboplatin)41.0

[back to top]

Progression-Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the ITT-WT Population

PFS is defined as the time between the date of randomization and the date of first documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first in the ITT-WT population. (NCT02367781)
Timeframe: Up to approximately 35 months after first patient enrolled

InterventionMonths (Median)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.0
Arm B (Nab-Paclitaxel+Carboplatin)5.5

[back to top]

Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms in the ITT-WT Population

Defined as time from randomization to confirmed deterioration (10-point change) on the combined European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core (EORTC QLQ-C30) and supplemental lung cancer module (EORTC QLQ-LC13) symptom subscales. (NCT02367781)
Timeframe: Up to approximately 35 months after first subject enrolled

InterventionMonths (Median)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)2.2
Arm B (Nab-Paclitaxel+Carboplatin)1.9

[back to top]

Minimum Observed Serum Concentration (Cmin) of Atezolizumab Prior to Infusion in Atezolizumab+Carboplain+Nab-Paclitaxel

Predose samples will be collected on the same day of treatment administration. (NCT02367781)
Timeframe: Cycle 1 Day 21, Cycle 2 Day 21, Cycle 3 Day 21, and Cycle 7 Day 21 (Cycle length = 21 days)

Interventionmcg/mL (Mean)
Cycle 1 Day 21Cycle 2 Day 21Cycle 3 Day 21Cycle 7 Day 21
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)70.9111134218

[back to top]

Percentage of Participants With Adverse Events

Percentage of participants with at least one adverse event. Adverse event onset date before cross over. (NCT02367781)
Timeframe: Up to approximately 69 months after first patient enrolled

InterventionPercentage of participants (Number)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)99.6
Arm B (Nab-Paclitaxel+Carboplatin)98.7

[back to top]

OS as Determined by the Investigator Using RECIST v1.1 in the PD-L1 Expression Population and PD-L1 Expression WT Population

OS is defined as the time between the date of randomization and date of death from any cause in the PD-L1 Expression Population and PD-L1 Expression WT Population. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. The PD-L1 expression WT population is defined as the PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation. (NCT02367781)
Timeframe: Up to approximately 35 months after first patient enrolled

,
InterventionMonths (Median)
TC1/2/3 or IC1/2/3 ITT PopulationTC1/2/3 or IC1/2/3 WT ITT Population
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)21.221.2
Arm B (Nab-Paclitaxel+Carboplatin)16.916.9

[back to top]

Percentage of Participants With an Objective Response (OR) (Complete Response [CR] or Partial Response [PR]) as Determined by the Investigator Using RECIST v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population

ORR (confirmation not required) is defined as proportion of participants with an objective response, either CR or PR, with the use of RECIST v1.1, as determined by investigator in ITT population, PD-L1 Expression population, and PD-L1 Expression WT population. ITT population was defined as all randomized participants, regardless of receipt of the assigned treatment. PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. PD-L1 expression WT population is defined as PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation. (NCT02367781)
Timeframe: Up to approximately 35 months after first subject enrolled

,
InterventionPercentage of participants (Number)
ITT PopulationTC1/2/3 or IC1/2/3 ITT WT PopulationTC1/2/3 or IC1/2/3 ITT Population
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)59.165.664.6
Arm B (Nab-Paclitaxel+Carboplatin)42.246.245.0

[back to top]

Overall Survival (OS) in the ITT-WT Population

OS is defined as the time between the date of randomization and date of death from any cause in the ITT-WT population. (NCT02367781)
Timeframe: Up to approximately 35 months after first patient enrolled

InterventionMonths (Median)
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)18.6
Arm B (Nab-Paclitaxel+Carboplatin)13.9

[back to top]

Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Atezolizumab

Baseline prevalence and post-baseline incidence of anti-drug antibodies (ADA) to Atezolizumab in the Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) and Arm B Carboplatin+nab-paclitaxel Crossover Participants (NCT02367781)
Timeframe: Up to approximately 35 months after first subject enrolled

,
InterventionPerecentage of participants (Number)
BaselinePost-baseline
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)3.122.4
Arm B (Nab-Paclitaxel+Carboplatin)4.823.5

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of≥0.5 points for chest pain score is considered to be clinically significant. (NCT02367781)
Timeframe: Up to approximately 35 months after first subject enrolled

InterventionUnits on a scale (Mean)
Chest Pain, Week 1Chest Pain, Week 2Chest Pain, Week 3Chest Pain, Week 4Chest Pain, Week 5Chest Pain, Week 6Chest Pain, Week 7Chest Pain, Week 8Chest Pain, Week 9Chest Pain, Week 10Chest Pain, Week 11Chest Pain, Week 12Chest Pain, Week 13Chest Pain, Week 14Chest Pain, Week 15Chest Pain, Week 16Chest Pain, Week 17Chest Pain, Week 18Chest Pain, Week 19Chest Pain, Week 20Chest Pain, Week 21Chest Pain, Week 22Chest Pain, Week 23Chest Pain, Week 24Chest Pain, Week 25Chest Pain, Week 26Chest Pain, Week 27Chest Pain, Week 28Chest Pain, Week 29Chest Pain, Week 30Chest Pain, Week 31Chest Pain, Week 32Chest Pain, Week 33Chest Pain, Week 34Chest Pain, Week 35Chest Pain, Week 36Chest Pain, Week 37Chest Pain, Week 38Chest Pain, Week 39Chest Pain, Week 40Chest Pain, Week 41Chest Pain, Week 42Chest Pain, Week 43Chest Pain, Week 44Chest Pain, Week 45Chest Pain, Week 46Chest Pain, Week 47Chest Pain, Week 48Chest Pain, Week 49Chest Pain, Week 50Chest Pain, Week 51Chest Pain, Week 52Chest Pain, Week 53Chest Pain, Week 54Chest Pain, Week 55Chest Pain, Week 56Chest Pain, Week 57Chest Pain, Week 58Chest Pain, Week 59Chest Pain, Week 60Chest Pain, Week 61Chest Pain, Week 62Chest Pain, Week 63Chest Pain, Week 64Chest Pain, Week 65Chest Pain, Week 66Chest Pain, Week 67Chest Pain, Week 68Chest Pain, Week 69Chest Pain, Week 70Chest Pain, Week 71Chest Pain, Week 72Chest Pain, Week 73Chest Pain, Week 74Chest Pain, Week 75Chest Pain, Week 76Chest Pain, Week 77Chest Pain, Week 78Chest Pain, Week 79Chest Pain, Week 80Chest Pain, Week 81Chest Pain, Week 82Chest Pain, Week 83Chest Pain, Week 84Chest Pain, Week 85Chest Pain, Week 86Chest Pain, Week 87Chest Pain, Week 88Chest Pain, Week 89Chest Pain, Week 90Chest Pain, Week 91Chest Pain, Week 92Chest Pain, Week 93Chest Pain, Survival Follow-Up Month 1Chest Pain, Survival Follow-Up Month 2Chest Pain, Survival Follow-Up Month 3Chest Pain, Survival Follow-Up Month 4Chest Pain, Survival Follow-Up Month 5Chest Pain, Survival Follow-Up Month 6Cough, Week 1Cough, Week 2Cough, Week 3Cough, Week 4Cough, Week 5Cough, Week 6Cough, Week 7Cough, Week 8Cough, Week 9Cough, Week 10Cough, Week 11Cough, Week 12Cough, Week 13Cough, Week 14Cough, Week 15Cough, Week 16Cough, Week 17Cough, Week 18Cough, Week 19Cough, Week 20Cough, Week 21Cough, Week 22Cough, Week 23Cough, Week 24Cough, Week 25Cough, Week 26Cough, Week 27Cough, Week 28Cough, Week 29Cough, Week 30Cough, Week 31Cough, Week 32Cough, Week 33Cough, Week 34Cough, Week 35Cough, Week 36Cough, Week 37Cough, Week 38Cough, Week 39Cough, Week 40Cough, Week 41Cough, Week 42Cough, Week 43Cough, Week 44Cough, Week 45Cough, Week 46Cough, Week 47Cough, Week 48Cough, Week 49Cough, Week 50Cough, Week 51Cough, Week 52Cough, Week 53Cough, Week 54Cough, Week 55Cough, Week 56Cough, Week 57Cough, Week 58Cough, Week 59Cough, Week 60Cough, Week 61Cough, Week 62Cough, Week 63Cough, Week 64Cough, Week 65Cough, Week 66Cough, Week 67Cough, Week 68Cough, Week 69Cough, Week 70Cough, Week 71Cough, Week 72Cough, Week 73Cough, Week 74Cough, Week 75Cough, Week 76Cough, Week 77Cough, Week 78Cough, Week 79Cough, Week 80Cough, Week 81Cough, Week 82Cough, Week 83Cough, Week 84Cough, Week 85Cough, Week 86Cough, Week 87Cough, Week 88Cough, Week 89Cough, Week 90Cough, Week 91Cough, Week 92Cough, Week 93Cough, Survival Follow-Up Month 1Cough, Survival Follow-Up Month 2Cough, Survival Follow-Up Month 3Cough, Survival Follow-Up Month 4Cough, Survival Follow-Up Month 5Cough, Survival Follow-Up Month 6Dyspnoea, Week 1Dyspnoea, Week 2Dyspnoea, Week 3Dyspnoea, Week 4Dyspnoea, Week 5Dyspnoea, Week 6Dyspnoea, Week 7Dyspnoea, Week 8Dyspnoea, Week 9Dyspnoea, Week 10Dyspnoea, Week 11Dyspnoea, Week 12Dyspnoea, Week 13Dyspnoea, Week 14Dyspnoea, Week 15Dyspnoea, Week 16Dyspnoea, Week 17Dyspnoea, Week 18Dyspnoea, Week 19Dyspnoea, Week 20Dyspnoea, Week 21Dyspnoea, Week 22Dyspnoea, Week 23Dyspnoea, Week 24Dyspnoea, Week 25Dyspnoea, Week 26Dyspnoea, Week 27Dyspnoea, Week 28Dyspnoea, Week 29Dyspnoea, Week 30Dyspnoea, Week 31Dyspnoea, Week 32Dyspnoea, Week 33Dyspnoea, Week 34Dyspnoea, Week 35Dyspnoea, Week 36Dyspnoea, Week 37Dyspnoea, Week 38Dyspnoea, Week 39Dyspnoea, Week 40Dyspnoea, Week 41Dyspnoea, Week 42Dyspnoea, Week 43Dyspnoea, Week 44Dyspnoea, Week 45Dyspnoea, Week 46Dyspnoea, Week 47Dyspnoea, Week 48Dyspnoea, Week 49Dyspnoea, Week 50Dyspnoea, Week 51Dyspnoea, Week 52Dyspnoea, Week 53Dyspnoea, Week 54Dyspnoea, Week 55Dyspnoea, Week 56Dyspnoea, Week 57Dyspnoea, Week 58Dyspnoea, Week 59Dyspnoea, Week 60Dyspnoea, Week 61Dyspnoea, Week 62Dyspnoea, Week 63Dyspnoea, Week 64Dyspnoea, Week 65Dyspnoea, Week 66Dyspnoea, Week 67Dyspnoea, Week 68Dyspnoea, Week 69Dyspnoea, Week 70Dyspnoea, Week 71Dyspnoea, Week 72Dyspnoea, Week 73Dyspnoea, Week 74Dyspnoea, Week 75Dyspnoea, Week 76Dyspnoea, Week 77Dyspnoea, Week 78Dyspnoea, Week 79Dyspnoea, Week 80Dyspnoea, Week 81Dyspnoea, Week 82Dyspnoea, Week 83Dyspnoea, Week 84Dyspnoea, Week 85Dyspnoea, Week 86Dyspnoea, Week 87Dyspnoea, Week 88Dyspnoea, Week 89Dyspnoea, Week 90Dyspnoea, Week 91Dyspnoea, Week 92Dyspnoea, Week 93Dyspnoea, Survival Follow-Up Month 1Dyspnoea, Survival Follow-Up Month 2Dyspnoea, Survival Follow-Up Month 3Dyspnoea, Survival Follow-Up Month 4Dyspnoea, Survival Follow-Up Month 5Dyspnoea, Survival Follow-Up Month 6
Arm B (Nab-Paclitaxel+Carboplatin)0.140.030.010.010.000.030.03-0.14-0.01-0.070.01-0.10-0.03-0.17-0.19-0.16-0.14-0.07-0.16-0.22-0.32-0.11-0.19-0.43-0.24-0.13-0.15-0.07-0.04-0.28-0.12-0.30-0.18-0.170.05-0.35-0.10-0.05-0.22-0.39-0.19-0.41-0.220.00-0.07-0.07-0.15-0.18-0.72-0.19-0.50-0.36-0.33-0.21-0.30-0.33-0.40-0.50-0.63-0.50-0.20-0.40-0.100.380.170.250.13-0.25-0.170.000.00-1.00-1.50-1.50-1.50-1.50-1.50-1.50-0.50-1.50-1.50-1.50-1.50-1.50-1.50-1.50-1.50-1.50-1.50-1.50-1.50-1.50-1.500.22-0.16-0.08-0.07-0.020.020.040.04-0.09-0.10-0.09-0.08-0.06-0.21-0.13-0.07-0.15-0.11-0.04-0.18-0.05-0.25-0.21-0.33-0.40-0.31-0.33-0.24-0.41-0.54-0.47-0.34-0.48-0.43-0.46-0.46-0.38-0.12-0.52-0.330.00-0.20-0.45-0.03-0.17-0.50-0.22-0.41-0.13-0.16-0.14-0.03-0.120.14-0.56-0.19-0.40-0.21-0.17-0.070.100.170.000.130.130.380.800.500.500.000.830.630.380.130.170.170.33-1.50-0.50-0.50-0.50-0.50-0.500.001.001.00-0.501.000.501.001.500.000.000.000.000.000.001.000.00-0.01-0.31-0.13-0.45-0.27-0.290.230.310.320.450.420.510.600.530.620.750.600.740.760.610.710.670.680.620.540.540.390.410.410.310.200.300.300.220.330.270.260.380.190.300.460.340.100.510.260.040.180.080.410.290.310.470.450.290.000.430.060.290.300.400.440.530.240.350.350.500.600.720.56-0.500.070.500.400.400.730.730.600.60-1.80-1.00-1.00-1.00-1.50-1.00-1.00-1.00-0.80-0.80-1.00-1.00-0.80-1.00-1.00-1.00-1.00-1.00-1.00-0.80-0.800.600.460.610.450.480.54

[back to top]

PFS as Determined by the Investigator Using Recist v1.1 in the ITT Population, PD-L1 Expression Population, and PD-L1 Expression WT Population

PFS is defined as the time between the date of randomization and the date of first documented disease progression as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurs first. The ITT population was defined as all randomized participants, regardless of receipt of the assigned treatment. The PD-L1 expression population is defined as one of the following: PD-L1 IHC TC1/2/3 or IC1/2/3 population, defined as ITT participants with PD-L1 IHC TC1/2/3 or IC1/2/3 expression in baseline tumor tissue; PD-L1 IHC TC2/3 or IC2/3 population, defined as ITT participants with PD-L1 IHC TC2/3 or IC2/3 expression in baseline tumor tissue; PD-L1 IHC TC3 or IC3 population, defined as ITT participants with PD-L1 IHC TC3 or IC3 expression in baseline tumor tissue. The PD-L1 expression WT population is defined as the PD-L1 expression population excluding participants with an activating EGFR mutation or ALK translocation. (NCT02367781)
Timeframe: Up to approximately 35 months after first subject enrolled

,
InterventionMonths (Median)
ITT PopulationTC1/2/3 or IC1/2/3 ITT PopulationTC1/2/3 or IC1/2/3-WT ITT Population
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)7.07.57.5
Arm B (Nab-Paclitaxel+Carboplatin)5.65.75.9

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms Score Using the Symptoms in Lung Cancer (SILC) Scale

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of≥0.5 points for chest pain score is considered to be clinically significant. (NCT02367781)
Timeframe: Up to approximately 35 months after first subject enrolled

InterventionUnits on a scale (Mean)
Chest Pain, Week 1Chest Pain, Week 2Chest Pain, Week 3Chest Pain, Week 4Chest Pain, Week 5Chest Pain, Week 6Chest Pain, Week 7Chest Pain, Week 8Chest Pain, Week 9Chest Pain, Week 10Chest Pain, Week 11Chest Pain, Week 12Chest Pain, Week 13Chest Pain, Week 14Chest Pain, Week 15Chest Pain, Week 16Chest Pain, Week 17Chest Pain, Week 18Chest Pain, Week 19Chest Pain, Week 20Chest Pain, Week 21Chest Pain, Week 22Chest Pain, Week 23Chest Pain, Week 24Chest Pain, Week 25Chest Pain, Week 26Chest Pain, Week 27Chest Pain, Week 28Chest Pain, Week 29Chest Pain, Week 30Chest Pain, Week 31Chest Pain, Week 32Chest Pain, Week 33Chest Pain, Week 34Chest Pain, Week 35Chest Pain, Week 36Chest Pain, Week 37Chest Pain, Week 38Chest Pain, Week 39Chest Pain, Week 40Chest Pain, Week 41Chest Pain, Week 42Chest Pain, Week 43Chest Pain, Week 44Chest Pain, Week 45Chest Pain, Week 46Chest Pain, Week 47Chest Pain, Week 48Chest Pain, Week 49Chest Pain, Week 50Chest Pain, Week 51Chest Pain, Week 52Chest Pain, Week 53Chest Pain, Week 54Chest Pain, Week 55Chest Pain, Week 56Chest Pain, Week 57Chest Pain, Week 58Chest Pain, Week 59Chest Pain, Week 60Chest Pain, Week 61Chest Pain, Week 62Chest Pain, Week 63Chest Pain, Week 64Chest Pain, Week 65Chest Pain, Week 66Chest Pain, Week 67Chest Pain, Week 68Chest Pain, Week 69Chest Pain, Week 70Chest Pain, Week 71Chest Pain, Week 72Chest Pain, Week 73Chest Pain, Week 74Chest Pain, Week 75Chest Pain, Week 76Chest Pain, Week 77Chest Pain, Week 78Chest Pain, Week 79Chest Pain, Week 80Chest Pain, Week 81Chest Pain, Week 82Chest Pain, Week 83Chest Pain, Week 84Chest Pain, Week 85Chest Pain, Week 86Chest Pain, Week 87Chest Pain, Week 88Chest Pain, Week 89Chest Pain, Week 90Chest Pain, Week 91Chest Pain, Week 92Chest Pain, Week 93Chest Pain, Week 94Chest Pain, Week 95Chest Pain, Week 96Chest Pain, Week 97Chest Pain, Week 98Chest Pain, Week 99Chest Pain, Week 100Chest Pain, Week 101Chest Pain, Week 102Chest Pain, Week 103Chest Pain, Week 104Chest Pain, Week 105Chest Pain, Week 106Chest Pain, Week 107Chest Pain, Week 108Chest Pain, Week 109Chest Pain, Week 110Chest Pain, Week 111Chest Pain, Week 112Chest Pain, Week 113Chest Pain, Week 114Chest Pain, Week 115Chest Pain, Week 116Chest Pain, Week 117Chest Pain, Week 118Chest Pain, Week 119Chest Pain, Week 120Chest Pain, Week 121Chest Pain, Week 122Chest Pain, Week 123Chest Pain, Week 124Chest Pain, Week 125Chest Pain, Survival Follow-Up Month 1Chest Pain, Survival Follow-Up Month 2Chest Pain, Survival Follow-Up Month 3Chest Pain, Survival Follow-Up Month 4Chest Pain, Survival Follow-Up Month 5Chest Pain, Survival Follow-Up Month 6Cough, Week 1Cough, Week 2Cough, Week 3Cough, Week 4Cough, Week 5Cough, Week 6Cough, Week 7Cough, Week 8Cough, Week 9Cough, Week 10Cough, Week 11Cough, Week 12Cough, Week 13Cough, Week 14Cough, Week 15Cough, Week 16Cough, Week 17Cough, Week 18Cough, Week 19Cough, Week 20Cough, Week 21Cough, Week 22Cough, Week 23Cough, Week 24Cough, Week 25Cough, Week 26Cough, Week 27Cough, Week 28Cough, Week 29Cough, Week 30Cough, Week 31Cough, Week 32Cough, Week 33Cough, Week 34Cough, Week 35Cough, Week 36Cough, Week 37Cough, Week 38Cough, Week 39Cough, Week 40Cough, Week 41Cough, Week 42Cough, Week 43Cough, Week 44Cough, Week 45Cough, Week 46Cough, Week 47Cough, Week 48Cough, Week 49Cough, Week 50Cough, Week 51Cough, Week 52Cough, Week 53Cough, Week 54Cough, Week 55Cough, Week 56Cough, Week 57Cough, Week 58Cough, Week 59Cough, Week 60Cough, Week 61Cough, Week 62Cough, Week 63Cough, Week 64Cough, Week 65Cough, Week 66Cough, Week 67Cough, Week 68Cough, Week 69Cough, Week 70Cough, Week 71Cough, Week 72Cough, Week 73Cough, Week 74Cough, Week 75Cough, Week 76Cough, Week 77Cough, Week 78Cough, Week 79Cough, Week 80Cough, Week 81Cough, Week 82Cough, Week 83Cough, Week 84Cough, Week 85Cough, Week 86Cough, Week 87Cough, Week 88Cough, Week 89Cough, Week 90Cough, Week 91Cough, Week 92Cough, Week 93Cough, Week 94Cough, Week 95Cough, Week 96Cough, Week 97Cough, Week 98Cough, Week 99Cough, Week 100Cough, Week 101Cough, Week 102Cough, Week 103Cough, Week 104Cough, Week 105Cough, Week 106Cough, Week 107Cough, Week 108Cough, Week 109Cough, Week 110Cough, Week 111Cough, Week 112Cough, Week 113Cough, Week 114Cough, Week 115Cough, Week 116Cough, Week 117Cough, Week 118Cough, Week 119Cough, Week 120Cough, Week 121Cough, Week 122Cough, Week 123Cough, Week 124Cough, Week 125Cough, Survival Follow-Up Month 1Cough, Survival Follow-Up Month 2Cough, Survival Follow-Up Month 3Cough, Survival Follow-Up Month 4Cough, Survival Follow-Up Month 5Cough, Survival Follow-Up Month 6Dyspnoea, Week 1Dyspnoea, Week 2Dyspnoea, Week 3Dyspnoea, Week 4Dyspnoea, Week 5Dyspnoea, Week 6Dyspnoea, Week 7Dyspnoea, Week 8Dyspnoea, Week 9Dyspnoea, Week 10Dyspnoea, Week 11Dyspnoea, Week 12Dyspnoea, Week 13Dyspnoea, Week 14Dyspnoea, Week 15Dyspnoea, Week 16Dyspnoea, Week 17Dyspnoea, Week 18Dyspnoea, Week 19Dyspnoea, Week 20Dyspnoea, Week 21Dyspnoea, Week 22Dyspnoea, Week 23Dyspnoea, Week 24Dyspnoea, Week 25Dyspnoea, Week 26Dyspnoea, Week 27Dyspnoea, Week 28Dyspnoea, Week 29Dyspnoea, Week 30Dyspnoea, Week 31Dyspnoea, Week 32Dyspnoea, Week 33Dyspnoea, Week 34Dyspnoea, Week 35Dyspnoea, Week 36Dyspnoea, Week 37Dyspnoea, Week 38Dyspnoea, Week 39Dyspnoea, Week 40Dyspnoea, Week 41Dyspnoea, Week 42Dyspnoea, Week 43Dyspnoea, Week 44Dyspnoea, Week 45Dyspnoea, Week 46Dyspnoea, Week 47Dyspnoea, Week 48Dyspnoea, Week 49Dyspnoea, Week 50Dyspnoea, Week 51Dyspnoea, Week 52Dyspnoea, Week 53Dyspnoea, Week 54Dyspnoea, Week 55Dyspnoea, Week 56Dyspnoea, Week 57Dyspnoea, Week 58Dyspnoea, Week 59Dyspnoea, Week 60Dyspnoea, Week 61Dyspnoea, Week 62Dyspnoea, Week 63Dyspnoea, Week 64Dyspnoea, Week 65Dyspnoea, Week 66Dyspnoea, Week 67Dyspnoea, Week 68Dyspnoea, Week 69Dyspnoea, Week 70Dyspnoea, Week 71Dyspnoea, Week 72Dyspnoea, Week 73Dyspnoea, Week 74Dyspnoea, Week 75Dyspnoea, Week 76Dyspnoea, Week 77Dyspnoea, Week 78Dyspnoea, Week 79Dyspnoea, Week 80Dyspnoea, Week 81Dyspnoea, Week 82Dyspnoea, Week 83Dyspnoea, Week 84Dyspnoea, Week 85Dyspnoea, Week 86Dyspnoea, Week 87Dyspnoea, Week 88Dyspnoea, Week 89Dyspnoea, Week 90Dyspnoea, Week 91Dyspnoea, Week 92Dyspnoea, Week 93Dyspnoea, Week 94Dyspnoea, Week 95Dyspnoea, Week 96Dyspnoea, Week 97Dyspnoea, Week 98Dyspnoea, Week 99Dyspnoea, Week 100Dyspnoea, Week 101Dyspnoea, Week 102Dyspnoea, Week 103Dyspnoea, Week 104Dyspnoea, Week 105Dyspnoea, Week 106Dyspnoea, Week 107Dyspnoea, Week 108Dyspnoea, Week 109Dyspnoea, Week 110Dyspnoea, Week 111Dyspnoea, Week 112Dyspnoea, Week 113Dyspnoea, Week 114Dyspnoea, Week 115Dyspnoea, Week 116Dyspnoea, Week 117Dyspnoea, Week 118Dyspnoea, Week 119Dyspnoea, Week 120Dyspnoea, Week 121Dyspnoea, Week 122Dyspnoea, Week 123Dyspnoea, Week 124Dyspnoea, Week 125Dyspnoea, Survival Follow-Up Month 1Dyspnoea, Survival Follow-Up Month 2Dyspnoea, Survival Follow-Up Month 3Dyspnoea, Survival Follow-Up Month 4Dyspnoea, Survival Follow-Up Month 5Dyspnoea, Survival Follow-Up Month 6
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)0.19-0.02-0.05-0.11-0.12-0.24-0.23-0.21-0.18-0.10-0.11-0.15-0.26-0.28-0.26-0.33-0.33-0.28-0.28-0.26-0.25-0.28-0.24-0.21-0.20-0.17-0.22-0.20-0.27-0.15-0.16-0.19-0.18-0.18-0.10-0.21-0.18-0.32-0.28-0.19-0.25-0.16-0.24-0.24-0.14-0.15-0.22-0.14-0.22-0.18-0.13-0.15-0.20-0.22-0.34-0.19-0.19-0.32-0.25-0.27-0.28-0.16-0.12-0.15-0.31-0.25-0.18-0.15-0.13-0.14-0.10-0.24-0.25-0.08-0.210.03-0.06-0.04-0.11-0.18-0.59-0.39-0.34-0.20-0.44-0.38-0.53-0.46-0.55-0.18-0.32-0.40-0.18-0.30-0.05-0.17-0.19-0.25-0.21-0.50-0.36-0.75-0.33-0.60-1.00-1.00-1.00-0.75-0.60-0.42-0.50-0.130.130.000.250.500.25-0.25-0.250.000.000.00-0.750.500.500.01-0.070.15-0.28-0.11-0.370.080.020.02-0.06-0.09-0.15-0.11-0.13-0.15-0.20-0.15-0.17-0.24-0.23-0.27-0.37-0.32-0.33-0.33-0.37-0.37-0.37-0.30-0.38-0.49-0.43-0.41-0.52-0.43-0.43-0.32-0.30-0.19-0.35-0.46-0.35-0.46-0.38-0.27-0.38-0.44-0.44-0.39-0.38-0.30-0.25-0.44-0.29-0.38-0.39-0.30-0.32-0.37-0.41-0.40-0.26-0.35-0.33-0.31-0.42-0.35-0.23-0.22-0.19-0.23-0.29-0.48-0.34-0.34-0.26-0.23-0.48-0.43-0.42-0.32-0.31-0.40-0.52-0.08-0.48-0.44-0.39-0.25-0.30-0.32-0.54-0.33-0.46-0.36-0.29-0.27-0.35-0.55-0.400.05-0.28-0.31-0.10-0.43-0.58-0.50-0.50-0.75-0.80-0.63-0.63-0.63-0.50-0.50-0.50-0.30-0.63-0.25-0.330.25-0.25-0.50-0.250.00-0.25-0.50-0.50-0.750.500.50-0.21-0.07-0.14-0.39-0.25-0.230.130.100.220.230.260.270.290.320.380.410.500.470.320.340.290.220.280.230.260.240.260.210.180.220.210.170.200.160.160.240.120.200.180.210.220.210.160.180.310.310.240.260.170.220.260.290.200.320.240.320.240.270.240.280.260.260.370.190.320.350.330.450.440.360.270.320.280.350.440.330.500.170.410.300.260.230.200.310.320.30-0.120.020.130.190.05-0.07-0.110.060.090.370.330.200.350.500.480.510.330.380.110.270.200.350.470.48-0.20-0.20-0.30-0.150.160.33-0.040.200.200.400.800.600.300.300.500.300.600.60-0.20-0.200.200.410.360.270.020.13-0.09

[back to top]

Plasma Concentrations of Carboplatin

(NCT02367781)
Timeframe: Predose (same day of treatment administration), 5-10 minutes before end of carboplatin infusion, 1 hour after carboplatin infusion (infusion duration=15 to 30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months)

,
Interventionng/mL (Mean)
Cycle 1 Day 1 Pre-doseCycle 1 Day 1 Before End of InfusionCycle 1 Day 1 Post InfusionCycle 3 Day 1 Pre-doseCycle 3 Day 1 Before End of InfusionCycle 3 Day 1 Post Infusion
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)NA20,50011,90016915,30011,400
Arm B (Nab-Paclitaxel+Carboplatin Crossover)NA17,00012,40016017,80013,400

[back to top]

Plasma Concentrations of Nab-Paclitaxel Reported as Total Paclitaxel

(NCT02367781)
Timeframe: Predose (same day of treatment administration), 5-10 minutes before end of nab-paclitaxel infusion, 1 hour after nab-paclitaxel infusion (infusion duration=30 minutes) on Day 1 of Cycle 1 and 3 (1 Cycle=21 days) (up to approximately 35 months)

,
Interventionng/mL (Mean)
Cycle 1 Day 1 Pre-doseCycle 1 Day 1 Before End of InfusionCycle 1 Day 1 Post InfusionCycle 3 Day 1 Pre-doseCycle 3 Day 1 Before End of InfusionCycle 3 Day 1 Post Infusion
Arm A (Atezolizumab+Nab-Paclitaxel+Carboplatin)NA3520307NA4480357
Arm B (Nab-Paclitaxel+Carboplatin Crossover)NA2530417NA2030447

[back to top]

OS in the TC2/3 or IC2/3 Population

OS is defined as the time between the date of randomization and date of death from any cause, in the TC2/3 or IC2/3 Population. (NCT02367794)
Timeframe: Up to approximately 39 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin14.5
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin20.4
Arm A: Atezolizumab + Paclitaxel + Carboplatin14.8

[back to top]

PFS as Determined by the Investigator Using RECIST v1.1 in the ITT Population (Arm A and Arm B)

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT Population Arm A and Arm B. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

InterventionMonths (Median)
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin6.5
Arm A: Atezolizumab + Paclitaxel + Carboplatin5.6

[back to top]

Percentage of Participants With Objective Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

Proportion of participants with an objective response (CR or PR) in the ITT population. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

InterventionPercentage of participants (Number)
Arm C: Nab-Paclitaxel + Carboplatin41.0
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin49.7
Arm A: Atezolizumab + Paclitaxel + Carboplatin49.3

[back to top]

Percentage of Participants With Adverse Events

Percentage of participants with at least one adverse event. (NCT02367794)
Timeframe: Up to approximately 68 months after first participant enrolled

InterventionPercentage of participants (Number)
Arm C: Nab-Paclitaxel + Carboplatin97.0
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin99.4
Arm A: Atezolizumab + Paclitaxel + Carboplatin97.9

[back to top]

Overall Survival (OS) in the ITT Population

OS is defined as the time between the date of randomization and date of death from any cause in the ITT population. (NCT02367794)
Timeframe: Up to approximately 39 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin13.5
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin14.2
Arm A: Atezolizumab + Paclitaxel + Carboplatin12.6

[back to top]

Plasma Concentrations for Nab-Paclitaxel

Plasma concentrations for nab-paclitaxel. (NCT02367794)
Timeframe: Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)

,
Interventionng/mL (Mean)
Cycle 1 Day 1 Prior to InfusionCycle 1 Day 1 Before End of InfusionCycle 1 Day 1 After InfusionCycle 3 Day 1 Prior to InfusionCycle 3 Day 1 Before End of InfusionCycle 3 Day 1 After Infusion
Arm B: Atezolizumab + Nab-Paclitaxel + CarboplatinNA3330735NA7160296
Arm C: Nab-Paclitaxel + CarboplatinNA8160921NA71801140

[back to top]

OS in the in the Teff Population

OS is defined as the time between the date of randomization and date of death from any cause in the in the Teff Population. (NCT02367794)
Timeframe: Up to approximately 39 months after first participant enrolled

,,
InterventionMonth (Median)
Teff >=-1.91Teff<-1.91
Arm A: Atezolizumab + Paclitaxel + Carboplatin15.210.5
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin17.413.0
Arm C: Nab-Paclitaxel + Carboplatin16.412.4

[back to top]

Percentage of Participants With Anti-therapeutic Antibody (ATA) Response to Atezolizumab

Percentage of participants with Anti-therapeutic Antibody (ATA) response to atezolizumab. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

,
InterventionPercentage of participants (Number)
Baseline evaluable participantsPost-baseline evaluable participants
Arm A: Atezolizumab + Paclitaxel + Carboplatin3.148.1
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin1.921.4

[back to top]

PFS as Determined by the Investigator Using RECIST v1.1 in the Teff Population

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the Teff Population. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

,,
InterventionMonths (Median)
Teff >=-1.91Teff<-1.91
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.05.5
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin7.06.2
Arm C: Nab-Paclitaxel + Carboplatin5.65.7

[back to top]

Plasma Concentrations for Carboplatin

Plasma concentrations for carboplatin. (NCT02367794)
Timeframe: Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 15 to 30 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)

,,
Interventionng/mL (Mean)
Cycle 1 Day 1 Prior to InfusionCycle 1 Day 1 Before End of InfusionCycle 1 Day 1 After InfusionCycle 3 Day 1 Prior to InfusionCycle 3 Day 1 Before End of InfusionCycle 3 Day 1 After Infusion
Arm A: Atezolizumab + Paclitaxel + CarboplatinNA21100119002383380020000
Arm B: Atezolizumab + Nab-Paclitaxel + CarboplatinNA1590098901472350011200
Arm C: Nab-Paclitaxel + CarboplatinNA24900108001612680014700

[back to top]

Plasma Concentrations for Paclitaxel

Plasma concentrations for paclitaxel. (NCT02367794)
Timeframe: Prior to infusion (within same day of treatment administration), 5-10 minutes before the end of infusion, and 1 hour after the end of infusion (infusion duration 180 minutes) on Day 1 of Cycles 1 and 3 (each cycle is 21 days)

Interventionng/mL (Mean)
Cycle 1 Day 1 Prior to InfusionCycle 1 Day 1 Before end of InfusionCycle 1 Day 1 After InfusionCycle 3 Day 1 Prior to InfusionCycle 3 Day 1 Before end of InfusionCycle 3 Day 1 After Infusion
Arm A: Atezolizumab + Paclitaxel + CarboplatinNA58602960NA2190011000

[back to top]

OS in the TC1/2/3 or IC1/2/3 Population

OS is defined as the time between the date of randomization and date of death from any cause in the TC1/2/3 or IC1/2/3 Population. (NCT02367794)
Timeframe: Up to approximately 39 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin15.0
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin14.8
Arm A: Atezolizumab + Paclitaxel + Carboplatin14.9

[back to top]

OS in the ITT Population (Arm A and Arm B)

OS is defined as the time between the date of randomization and date of death from any cause in the ITT Population, Arm A and Arm B. (NCT02367794)
Timeframe: Up to approximately 39 months after first participant enrolled

InterventionMonths (Median)
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin14.2
Arm A: Atezolizumab + Paclitaxel + Carboplatin12.6

[back to top]

Duration of Response as Determined by the Investigator Using RECIST v1.1 in the ITT Population

Duration of response is defined as the time from the first documented objective response to documented PD or death from any cause, whichever occurred first, in the ITT Population. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin5.2
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin7.2
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.0

[back to top]

Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for chest pain score is considered to be clinically significant. (Note: PD=progression of disease) (NCT02367794)
Timeframe: Baseline up to approximately 30 months after first participant enrolled

InterventionUnits on a scale (Mean)
Chest Pain, Week 1Chest Pain, Week 2Chest Pain, Week 3Chest Pain, Week 4Chest Pain, Week 5Chest Pain, Week 6Chest Pain, Week 7Chest Pain, Week 8Chest Pain, Week 9Chest Pain, Week 10Chest Pain, Week 11Chest Pain, Week 12Chest Pain, Week 13Chest Pain, Week 14Chest Pain, Week 15Chest Pain, Week 16Chest Pain, Week 17Chest Pain, Week 18Chest Pain, Week 19Chest Pain, Week 20Chest Pain, Week 21Chest Pain, Week 22Chest Pain, Week 23Chest Pain, Week 24Chest Pain, Week 25Chest Pain, Week 26Chest Pain, Week 27Chest Pain, Week 28Chest Pain, Week 29Chest Pain, Week 30Chest Pain, Week 31Chest Pain, Week 32Chest Pain, Week 33Chest Pain, Week 34Chest Pain, Week 35Chest Pain, Week 36Chest Pain, Week 37Chest Pain, Week 38Chest Pain, Week 39Chest Pain, Week 40Chest Pain, Week 41Chest Pain, Week 42Chest Pain, Week 43Chest Pain, Week 44Chest Pain, Week 45Chest Pain, Week 46Chest Pain, Week 47Chest Pain, Week 48Chest Pain, Week 49Chest Pain, Week 50Chest Pain, Week 51Chest Pain, Week 52Chest Pain, Week 53Chest Pain, Week 54Chest Pain, Week 55Chest Pain, Week 56Chest Pain, Week 57Chest Pain, Week 58Chest Pain, Week 59Chest Pain, Week 60Chest Pain, Week 61Chest Pain, Week 62Chest Pain, Week 63Chest Pain, Week 64Chest Pain, Week 65Chest Pain, Week 66Chest Pain, Week 67Chest Pain, Week 68Chest Pain, Week 69Chest Pain, Week 70Chest Pain, Week 71Chest Pain, Week 72Chest Pain, Week 73Chest Pain, Week 74Chest Pain, Week 75Chest Pain, Week 76Chest Pain, Week 77Chest Pain, Week 78Chest Pain, Week 79Chest Pain, Week 80Chest Pain, Week 81Chest Pain, Week 82Chest Pain, Week 83Chest Pain, Week 84Chest Pain, Week 85Chest Pain, Week 86Chest Pain, Week 87Chest Pain, Week 88Chest Pain, Week 89Chest Pain, Week 90Chest Pain, Week 91Chest Pain, Week 92Chest Pain, Week 93Chest Pain, Week 94Chest Pain, Week 95Chest Pain, Week 96Chest Pain, Week 97Chest Pain, Week 98Chest Pain, Week 99Chest Pain, Week 100Chest Pain, Week 101Chest Pain, Week 102Chest Pain, Week 103Chest Pain, Week 104Chest Pain, Week 105Chest Pain, Week 106Chest Pain, Week 107Chest Pain, Week 108Chest Pain, Week 109Chest Pain, Week 110Chest Pain, Week 111Chest Pain, Week 112Chest Pain, Week 113Chest Pain, Week 114Chest Pain, Week 115Chest Pain, Week 116Chest Pain, Week 117Chest Pain, Week 118Chest Pain, Week 119Chest Pain, Week 120Chest Pain, Week 121Chest Pain, Week 122Chest Pain, Week 123Chest Pain, Week 124Chest Pain, Time of First PdChest Pain, Time of Last Tx DoseCough, Week 1Cough, Week 2Cough, Week 3Cough, Week 4Cough, Week 5Cough, Week 6Cough, Week 7Cough, Week 8Cough, Week 9Cough, Week 10Cough, Week 11Cough, Week 12Cough, Week 13Cough, Week 14Cough, Week 15Cough, Week 16Cough, Week 17Cough, Week 18Cough, Week 19Cough, Week 20Cough, Week 21Cough, Week 22Cough, Week 23Cough, Week 24Cough, Week 25Cough, Week 26Cough, Week 27Cough, Week 28Cough, Week 29Cough, Week 30Cough, Week 31Cough, Week 32Cough, Week 33Cough, Week 34Cough, Week 35Cough, Week 36Cough, Week 37Cough, Week 38Cough, Week 39Cough, Week 40Cough, Week 41Cough, Week 42Cough, Week 43Cough, Week 44Cough, Week 45Cough, Week 46Cough, Week 47Cough, Week 48Cough, Week 49Cough, Week 50Cough, Week 51Cough, Week 52Cough, Week 53Cough, Week 54Cough, Week 55Cough, Week 56Cough, Week 57Cough, Week 58Cough, Week 59Cough, Week 60Cough, Week 61Cough, Week 62Cough, Week 63Cough, Week 64Cough, Week 65Cough, Week 66Cough, Week 67Cough, Week 68Cough, Week 69Cough, Week 70Cough, Week 71Cough, Week 72Cough, Week 73Cough, Week 74Cough, Week 75Cough, Week 76Cough, Week 77Cough, Week 78Cough, Week 79Cough, Week 80Cough, Week 81Cough, Week 82Cough, Week 83Cough, Week 84Cough, Week 85Cough, Week 86Cough, Week 87Cough, Week 88Cough, Week 89Cough, Week 90Cough, Week 91Cough, Week 92Cough, Week 93Cough, Week 94Cough, Week 95Cough, Week 96Cough, Week 97Cough, Week 98Cough, Week 99Cough, Week 100Cough, Week 101Cough, Week 102Cough, Week 103Cough, Week 104Cough, Week 105Cough, Week 106Cough, Week 107Cough, Week 108Cough, Week 109Cough, Week 110Cough, Week 111Cough, Week 112Cough, Week 113Cough, Week 114Cough, Week 115Cough, Week 116Cough, Week 117Cough, Week 118Cough, Week 119Cough, Week 120Cough, Week 121Cough, Week 122Cough, Week 123Cough, Week 124Cough, Time of First PdCough, Time of Last Tx DoseDyspnoea, Week 1Dyspnoea, Week 2Dyspnoea, Week 3Dyspnoea, Week 4Dyspnoea, Week 5Dyspnoea, Week 6Dyspnoea, Week 7Dyspnoea, Week 8Dyspnoea, Week 9Dyspnoea, Week 10Dyspnoea, Week 11Dyspnoea, Week 12Dyspnoea, Week 13Dyspnoea, Week 14Dyspnoea, Week 15Dyspnoea, Week 16Dyspnoea, Week 17Dyspnoea, Week 18Dyspnoea, Week 19Dyspnoea, Week 20Dyspnoea, Week 21Dyspnoea, Week 22Dyspnoea, Week 23Dyspnoea, Week 24Dyspnoea, Week 25Dyspnoea, Week 26Dyspnoea, Week 27Dyspnoea, Week 28Dyspnoea, Week 29Dyspnoea, Week 30Dyspnoea, Week 31Dyspnoea, Week 32Dyspnoea, Week 33Dyspnoea, Week 34Dyspnoea, Week 35Dyspnoea, Week 36Dyspnoea, Week 37Dyspnoea, Week 38Dyspnoea, Week 39Dyspnoea, Week 40Dyspnoea, Week 41Dyspnoea, Week 42Dyspnoea, Week 43Dyspnoea, Week 44Dyspnoea, Week 45Dyspnoea, Week 46Dyspnoea, Week 47Dyspnoea, Week 48Dyspnoea, Week 49Dyspnoea, Week 50Dyspnoea, Week 51Dyspnoea, Week 52Dyspnoea, Week 53Dyspnoea, Week 54Dyspnoea, Week 55Dyspnoea, Week 56Dyspnoea, Week 57Dyspnoea, Week 58Dyspnoea, Week 59Dyspnoea, Week 60Dyspnoea, Week 61Dyspnoea, Week 62Dyspnoea, Week 63Dyspnoea, Week 64Dyspnoea, Week 65Dyspnoea, Week 66Dyspnoea, Week 67Dyspnoea, Week 68Dyspnoea, Week 69Dyspnoea, Week 70Dyspnoea, Week 71Dyspnoea, Week 72Dyspnoea, Week 73Dyspnoea, Week 74Dyspnoea, Week 75Dyspnoea, Week 76Dyspnoea, Week 77Dyspnoea, Week 78Dyspnoea, Week 79Dyspnoea, Week 80Dyspnoea, Week 81Dyspnoea, Week 82Dyspnoea, Week 83Dyspnoea, Week 84Dyspnoea, Week 85Dyspnoea, Week 86Dyspnoea, Week 87Dyspnoea, Week 88Dyspnoea, Week 89Dyspnoea, Week 90Dyspnoea, Week 91Dyspnoea, Week 92Dyspnoea, Week 93Dyspnoea, Week 94Dyspnoea, Week 95Dyspnoea, Week 96Dyspnoea, Week 97Dyspnoea, Week 98Dyspnoea, Week 99Dyspnoea, Week 100Dyspnoea, Week 101Dyspnoea, Week 102Dyspnoea, Week 103Dyspnoea, Week 104Dyspnoea, Week 105Dyspnoea, Week 106Dyspnoea, Week 107Dyspnoea, Week 108Dyspnoea, Week 109Dyspnoea, Week 110Dyspnoea, Week 111Dyspnoea, Week 112Dyspnoea, Week 113Dyspnoea, Week 114Dyspnoea, Week 115Dyspnoea, Week 116Dyspnoea, Week 117Dyspnoea, Week 118Dyspnoea, Week 119Dyspnoea, Week 120Dyspnoea, Week 121Dyspnoea, Week 122Dyspnoea, Week 123Dyspnoea, Week 124Dyspnoea, Time of First PdDyspnoea, Time of Last Tx Dose
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin0.140.09-0.03-0.05-0.08-0.13-0.18-0.17-0.19-0.16-0.24-0.21-0.22-0.24-0.28-0.14-0.17-0.13-0.10-0.15-0.07-0.080.04-0.15-0.17-0.06-0.17-0.12-0.11-0.21-0.16-0.15-0.20-0.04-0.14-0.060.05-0.09-0.18-0.11-0.14-0.05-0.08-0.25-0.21-0.16-0.16-0.17-0.24-0.17-0.16-0.09-0.12-0.18-0.11-0.22-0.22-0.22-0.20-0.27-0.23-0.03-0.12-0.13-0.130.00-0.08-0.09-0.15-0.06-0.13-0.20-0.02-0.10-0.17-0.020.00-0.11-0.13-0.35-0.25-0.31-0.32-0.33-0.35-0.37-0.25-0.20-0.14-0.04-0.42-0.150.00-0.230.140.09-0.180.050.00-0.15-0.10-0.25-0.56-0.56-0.50-0.72-0.57-0.30-0.90-0.50-0.25-0.67-0.50-0.50-0.50-0.67-1.000.000.000.000.000.000.000.000.100.010.030.00-0.10-0.16-0.24-0.22-0.27-0.26-0.27-0.28-0.27-0.25-0.28-0.29-0.23-0.18-0.21-0.34-0.29-0.24-0.26-0.27-0.30-0.33-0.31-0.32-0.39-0.36-0.33-0.31-0.34-0.41-0.35-0.34-0.38-0.39-0.22-0.36-0.46-0.39-0.43-0.41-0.38-0.48-0.32-0.38-0.38-0.41-0.44-0.29-0.22-0.33-0.28-0.45-0.38-0.46-0.36-0.51-0.45-0.41-0.38-0.29-0.30-0.27-0.28-0.30-0.44-0.21-0.26-0.28-0.15-0.19-0.22-0.22-0.170.07-0.18-0.30-0.04-0.45-0.31-0.33-0.39-0.10-0.24-0.270.00-0.37-0.29-0.35-0.58-0.19-0.42-0.410.00-0.18-0.14-0.350.00-0.35-0.200.00-0.56-0.380.08-0.28-0.57-0.70-0.300.50-0.130.170.130.50-0.88-0.50-0.251.001.001.001.001.001.002.00-0.16-0.240.110.110.160.160.250.230.250.290.260.340.310.410.320.290.320.320.250.280.280.280.230.250.300.200.180.310.210.170.190.120.180.090.020.050.040.110.160.100.040.240.130.050.160.110.200.080.060.140.060.100.080.110.110.110.150.140.120.020.110.060.050.010.100.070.050.040.040.010.060.160.220.250.100.100.050.250.040.090.16-0.13-0.02-0.05-0.08-0.17-0.16-0.230.08-0.21-0.13-0.32-0.52-0.28-0.23-0.38-0.07-0.02-0.22-0.18-0.26-0.24-0.26-0.67-0.60-0.63-0.20-0.24-0.17-0.36-0.40-0.27-0.15-0.20-0.35-0.27-0.40-0.20-0.60-0.80-0.80-0.80-0.80-0.80-0.80-0.800.420.28

[back to top]

TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-LC13 Symptom Subscales in the ITT Population

TTD was documented for a 3-symptom composite endpoint using the following EORTC QLQ-LC13 symptom scores: cough, chest pain, and dyspnea multi--item scale. In this instance, symptom deterioration will be determined as a >= 10-point increase above baseline in any of the listed symptom scores, whichever occurs first (cough, chest pain, and dyspnea multi-item scale). Confirmed clinically meaningful symptom deterioration will need to be held for the original symptom; a >= 10-point increase above baseline in a symptom score must be held for at least two consecutive assessments or an initial>=10-point increase above baseline followed by death within 3 weeks from the last assessment. A >= 10-point change in the EORTC scale score is perceived by patients as clinically significant. (NCT02367794)
Timeframe: Up to approximately 30 months after the first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin2.6
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin3.4
Arm A: Atezolizumab + Paclitaxel + Carboplatin2.8

[back to top]

Minimum Observed Serum Atezolizumab Concentration (Cmin)

Minimum observed serum atezolizumab concentration (Cmin). The predose samples will be collected on the same day of treatment administration. (NCT02367794)
Timeframe: Predose on Day 1 of Cycles 1-4, 8, 16, every 8 cycle thereafter (up to 30 months), at treatment discontinuation (up to 30 months), and at 120 days after the last dose of atezolizumab (up to approximately 30 months, each cycle is 21 days)

,
Interventionµg/mL (Mean)
Cycle 1 Day 1Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 8 Day 1Cycle 16 Day 1Cycle 24 Day 1Cycle 32 Day 1Cycle 40 Day 1Treatment Discontinuation VisitDay 120 Post Last Dose
Arm A: Atezolizumab + Paclitaxel + CarboplatinNA63.91031281882011872423081267.81
Arm B: Atezolizumab + Nab-Paclitaxel + CarboplatinNA69.51071261902122242101741379.47

[back to top]

Maximum Observed Serum Atezolizumab Concentration (Cmax)

Maximum observed serum atezolizumab concentration (Cmax). The predose samples will be collected on the same day of treatment administration. The infusion duration of atezolizumab will be of 30-60 minutes. (NCT02367794)
Timeframe: Cycle 1 Day 1 and Cycle 3 Day 1 (Cycle length = 21 days)

,
Interventionµg/mL (Mean)
Cycle 1 Day 1 Post doseCycle 3 Day 1 Post dose
Arm A: Atezolizumab + Paclitaxel + Carboplatin372470
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin378444

[back to top]

Event Free Rate at 1 and 2 Years in the ITT Population

Event free rate at 1 and 2 years is defined as the proportion of participants alive at 1 and 2 years after randomization estimated using Kaplan-Meier (KM) methodology for the ITT population. (NCT02367794)
Timeframe: 1 and 2 years

,,
InterventionPercentage of participants (Number)
1 Year2 Year
Arm A: Atezolizumab + Paclitaxel + Carboplatin52.3027.79
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin56.3432.51
Arm C: Nab-Paclitaxel + Carboplatin56.2826.58

[back to top]

Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for chest pain score is considered to be clinically significant. (Note: PD=progression of disease) (NCT02367794)
Timeframe: Baseline up to approximately 30 months after first participant enrolled

InterventionUnits on a scale (Mean)
Chest Pain, Week 1Chest Pain, Week 2Chest Pain, Week 3Chest Pain, Week 4Chest Pain, Week 5Chest Pain, Week 6Chest Pain, Week 7Chest Pain, Week 8Chest Pain, Week 9Chest Pain, Week 10Chest Pain, Week 11Chest Pain, Week 12Chest Pain, Week 13Chest Pain, Week 14Chest Pain, Week 15Chest Pain, Week 16Chest Pain, Week 17Chest Pain, Week 18Chest Pain, Week 19Chest Pain, Week 20Chest Pain, Week 21Chest Pain, Week 22Chest Pain, Week 23Chest Pain, Week 24Chest Pain, Week 25Chest Pain, Week 26Chest Pain, Week 27Chest Pain, Week 28Chest Pain, Week 29Chest Pain, Week 30Chest Pain, Week 31Chest Pain, Week 32Chest Pain, Week 33Chest Pain, Week 34Chest Pain, Week 35Chest Pain, Week 36Chest Pain, Week 37Chest Pain, Week 38Chest Pain, Week 39Chest Pain, Week 40Chest Pain, Week 41Chest Pain, Week 42Chest Pain, Week 43Chest Pain, Week 44Chest Pain, Week 45Chest Pain, Week 46Chest Pain, Week 47Chest Pain, Week 48Chest Pain, Week 49Chest Pain, Week 50Chest Pain, Week 51Chest Pain, Week 52Chest Pain, Week 53Chest Pain, Week 54Chest Pain, Week 55Chest Pain, Week 56Chest Pain, Week 57Chest Pain, Week 58Chest Pain, Week 59Chest Pain, Week 60Chest Pain, Week 61Chest Pain, Week 62Chest Pain, Week 63Chest Pain, Week 64Chest Pain, Week 65Chest Pain, Week 66Chest Pain, Week 67Chest Pain, Week 68Chest Pain, Week 69Chest Pain, Week 70Chest Pain, Week 71Chest Pain, Week 72Chest Pain, Week 73Chest Pain, Week 74Chest Pain, Week 75Chest Pain, Week 76Chest Pain, Week 77Chest Pain, Week 78Chest Pain, Week 79Chest Pain, Week 80Chest Pain, Week 81Chest Pain, Week 82Chest Pain, Week 83Chest Pain, Week 84Chest Pain, Week 85Chest Pain, Week 86Chest Pain, Week 87Chest Pain, Week 88Chest Pain, Week 89Chest Pain, Week 90Chest Pain, Week 91Chest Pain, Week 92Chest Pain, Week 93Chest Pain, Week 94Chest Pain, Week 95Chest Pain, Week 96Chest Pain, Week 97Chest Pain, Week 98Chest Pain, Week 99Chest Pain, Week 100Chest Pain, Week 101Chest Pain, Week 102Chest Pain, Week 103Chest Pain, Week 104Chest Pain, Week 105Chest Pain, Week 106Chest Pain, Week 107Chest Pain, Week 108Chest Pain, Week 109Chest Pain, Week 110Chest Pain, Week 111Chest Pain, Week 112Chest Pain, Week 113Chest Pain, Week 114Chest Pain, Week 115Chest Pain, Week 116Chest Pain, Week 117Chest Pain, Week 118Chest Pain, Week 119Chest Pain, Week 120Chest Pain, Week 121Chest Pain, Week 122Chest Pain, Week 123Chest Pain, Week 124Chest Pain, Week 125Chest Pain, Week 126Chest Pain, Week 127Chest Pain, Time of First PdChest Pain, Time of Last Tx DoseCough, Week 1Cough, Week 2Cough, Week 3Cough, Week 4Cough, Week 5Cough, Week 6Cough, Week 7Cough, Week 8Cough, Week 9Cough, Week 10Cough, Week 11Cough, Week 12Cough, Week 13Cough, Week 14Cough, Week 15Cough, Week 16Cough, Week 17Cough, Week 18Cough, Week 19Cough, Week 20Cough, Week 21Cough, Week 22Cough, Week 23Cough, Week 24Cough, Week 25Cough, Week 26Cough, Week 27Cough, Week 28Cough, Week 29Cough, Week 30Cough, Week 31Cough, Week 32Cough, Week 33Cough, Week 34Cough, Week 35Cough, Week 36Cough, Week 37Cough, Week 38Cough, Week 39Cough, Week 40Cough, Week 41Cough, Week 42Cough, Week 43Cough, Week 44Cough, Week 45Cough, Week 46Cough, Week 47Cough, Week 48Cough, Week 49Cough, Week 50Cough, Week 51Cough, Week 52Cough, Week 53Cough, Week 54Cough, Week 55Cough, Week 56Cough, Week 57Cough, Week 58Cough, Week 59Cough, Week 60Cough, Week 61Cough, Week 62Cough, Week 63Cough, Week 64Cough, Week 65Cough, Week 66Cough, Week 67Cough, Week 68Cough, Week 69Cough, Week 70Cough, Week 71Cough, Week 72Cough, Week 73Cough, Week 74Cough, Week 75Cough, Week 76Cough, Week 77Cough, Week 78Cough, Week 79Cough, Week 80Cough, Week 81Cough, Week 82Cough, Week 83Cough, Week 84Cough, Week 85Cough, Week 86Cough, Week 87Cough, Week 88Cough, Week 89Cough, Week 90Cough, Week 91Cough, Week 92Cough, Week 93Cough, Week 94Cough, Week 95Cough, Week 96Cough, Week 97Cough, Week 98Cough, Week 99Cough, Week 100Cough, Week 101Cough, Week 102Cough, Week 103Cough, Week 104Cough, Week 105Cough, Week 106Cough, Week 107Cough, Week 108Cough, Week 109Cough, Week 110Cough, Week 111Cough, Week 112Cough, Week 113Cough, Week 114Cough, Week 115Cough, Week 116Cough, Week 117Cough, Week 118Cough, Week 119Cough, Week 120Cough, Week 121Cough, Week 122Cough, Week 123Cough, Week 124Cough, Week 125Cough, Week 126Cough, Week 127Cough, Time of First PdCough, Time of Last Tx DoseDyspnoea, Week 1Dyspnoea, Week 2Dyspnoea, Week 3Dyspnoea, Week 4Dyspnoea, Week 5Dyspnoea, Week 6Dyspnoea, Week 7Dyspnoea, Week 8Dyspnoea, Week 9Dyspnoea, Week 10Dyspnoea, Week 11Dyspnoea, Week 12Dyspnoea, Week 13Dyspnoea, Week 14Dyspnoea, Week 15Dyspnoea, Week 16Dyspnoea, Week 17Dyspnoea, Week 18Dyspnoea, Week 19Dyspnoea, Week 20Dyspnoea, Week 21Dyspnoea, Week 22Dyspnoea, Week 23Dyspnoea, Week 24Dyspnoea, Week 25Dyspnoea, Week 26Dyspnoea, Week 27Dyspnoea, Week 28Dyspnoea, Week 29Dyspnoea, Week 30Dyspnoea, Week 31Dyspnoea, Week 32Dyspnoea, Week 33Dyspnoea, Week 34Dyspnoea, Week 35Dyspnoea, Week 36Dyspnoea, Week 37Dyspnoea, Week 38Dyspnoea, Week 39Dyspnoea, Week 40Dyspnoea, Week 41Dyspnoea, Week 42Dyspnoea, Week 43Dyspnoea, Week 44Dyspnoea, Week 45Dyspnoea, Week 46Dyspnoea, Week 47Dyspnoea, Week 48Dyspnoea, Week 49Dyspnoea, Week 50Dyspnoea, Week 51Dyspnoea, Week 52Dyspnoea, Week 53Dyspnoea, Week 54Dyspnoea, Week 55Dyspnoea, Week 56Dyspnoea, Week 57Dyspnoea, Week 58Dyspnoea, Week 59Dyspnoea, Week 60Dyspnoea, Week 61Dyspnoea, Week 62Dyspnoea, Week 63Dyspnoea, Week 64Dyspnoea, Week 65Dyspnoea, Week 66Dyspnoea, Week 67Dyspnoea, Week 68Dyspnoea, Week 69Dyspnoea, Week 70Dyspnoea, Week 71Dyspnoea, Week 72Dyspnoea, Week 73Dyspnoea, Week 74Dyspnoea, Week 75Dyspnoea, Week 76Dyspnoea, Week 77Dyspnoea, Week 78Dyspnoea, Week 79Dyspnoea, Week 80Dyspnoea, Week 81Dyspnoea, Week 82Dyspnoea, Week 83Dyspnoea, Week 84Dyspnoea, Week 85Dyspnoea, Week 86Dyspnoea, Week 87Dyspnoea, Week 88Dyspnoea, Week 89Dyspnoea, Week 90Dyspnoea, Week 91Dyspnoea, Week 92Dyspnoea, Week 93Dyspnoea, Week 94Dyspnoea, Week 95Dyspnoea, Week 96Dyspnoea, Week 97Dyspnoea, Week 98Dyspnoea, Week 99Dyspnoea, Week 100Dyspnoea, Week 101Dyspnoea, Week 102Dyspnoea, Week 103Dyspnoea, Week 104Dyspnoea, Week 105Dyspnoea, Week 106Dyspnoea, Week 107Dyspnoea, Week 108Dyspnoea, Week 109Dyspnoea, Week 110Dyspnoea, Week 111Dyspnoea, Week 112Dyspnoea, Week 113Dyspnoea, Week 114Dyspnoea, Week 115Dyspnoea, Week 116Dyspnoea, Week 117Dyspnoea, Week 118Dyspnoea, Week 119Dyspnoea, Week 120Dyspnoea, Week 121Dyspnoea, Week 122Dyspnoea, Week 123Dyspnoea, Week 124Dyspnoea, Week 125Dyspnoea, Week 126Dyspnoea, Week 127Dyspnoea, Time of First PdDyspnoea, Time of Last Tx Dose
Arm A: Atezolizumab + Paclitaxel + Carboplatin0.440.28-0.050.09-0.16-0.20-0.14-0.17-0.21-0.08-0.09-0.30-0.17-0.15-0.17-0.23-0.24-0.17-0.16-0.17-0.18-0.14-0.10-0.17-0.20-0.110.04-0.19-0.18-0.08-0.15-0.16-0.100.02-0.19-0.06-0.08-0.14-0.13-0.06-0.13-0.110.05-0.10-0.05-0.070.040.00-0.09-0.14-0.190.02-0.20-0.24-0.15-0.08-0.27-0.24-0.28-0.26-0.34-0.36-0.55-0.42-0.25-0.47-0.43-0.53-0.03-0.32-0.43-0.14-0.08-0.38-0.21-0.21-0.050.000.170.090.220.22-0.050.350.300.330.130.00-0.290.000.140.19-0.050.000.250.19-0.110.000.070.000.210.080.170.000.00-0.40-0.50-0.380.25-0.38-0.38-1.00-0.67-1.00-0.67-0.67-1.00-1.00-1.00-1.00-1.00-1.00-1.00-0.50-0.50-0.50-1.00-0.110.05-0.020.17-0.08-0.33-0.19-0.35-0.47-0.36-0.34-0.42-0.50-0.46-0.46-0.50-0.47-0.52-0.48-0.48-0.37-0.51-0.46-0.44-0.45-0.46-0.52-0.54-0.31-0.52-0.48-0.54-0.49-0.53-0.53-0.41-0.47-0.43-0.54-0.45-0.50-0.47-0.58-0.68-0.45-0.56-0.69-0.67-0.54-0.55-0.63-0.72-0.69-0.64-0.53-0.63-0.68-0.51-0.74-0.67-0.81-0.69-0.84-0.78-0.82-0.81-0.70-0.82-0.78-0.66-0.78-0.92-0.90-0.72-1.00-1.04-1.04-1.18-0.60-0.86-0.61-0.95-0.72-0.44-1.00-0.90-0.60-0.42-0.94-1.29-1.14-0.79-0.93-0.94-0.90-0.88-0.81-1.00-0.78-1.00-0.64-0.81-0.79-0.75-0.670.00-0.25-0.80-1.25-1.38-0.75-1.25-1.25-1.75-1.17-1.50-1.00-1.33-1.50-1.50-1.00-1.00-1.00-1.25-2.00-1.00-2.00-1.00-1.00-0.16-0.210.170.270.300.260.310.290.270.310.330.340.350.290.340.340.300.360.290.340.440.240.190.240.200.290.250.390.360.300.310.390.360.260.310.300.380.370.320.400.360.370.330.290.410.330.270.260.310.220.140.060.150.340.110.100.160.120.130.12-0.030.02-0.18-0.04-0.06-0.22-0.18-0.18-0.24-0.11-0.20-0.18-0.01-0.06-0.11-0.17-0.22-0.130.12-0.20-0.130.00-0.040.00-0.40-0.22-0.16-0.17-0.25-0.51-0.06-0.17-0.17-0.10-0.14-0.25-0.20-0.180.04-0.29-0.29-0.20-0.030.00-0.03-0.350.23-0.04-0.30-0.400.10-0.40-0.45-1.30-0.47-1.30-0.67-0.73-1.20-1.20-1.40-1.10-1.30-1.30-1.00-1.20-1.00-1.20-1.200.270.28

[back to top]

Change From Baseline in Patient-reported Lung Cancer Symptoms Score Using the SILC Scale Symptom Severity Score in the ITT Population

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of ≥0.5 points for chest pain score is considered to be clinically significant. (Note: PD=progression of disease) (NCT02367794)
Timeframe: Baseline up to approximately 30 months after first participant enrolled

InterventionUnits on a scale (Mean)
Chest Pain, Week 1Chest Pain, Week 2Chest Pain, Week 3Chest Pain, Week 4Chest Pain, Week 5Chest Pain, Week 6Chest Pain, Week 7Chest Pain, Week 8Chest Pain, Week 9Chest Pain, Week 10Chest Pain, Week 11Chest Pain, Week 12Chest Pain, Week 13Chest Pain, Week 14Chest Pain, Week 15Chest Pain, Week 16Chest Pain, Week 17Chest Pain, Week 18Chest Pain, Week 19Chest Pain, Week 20Chest Pain, Week 21Chest Pain, Week 22Chest Pain, Week 23Chest Pain, Week 24Chest Pain, Week 25Chest Pain, Week 26Chest Pain, Week 27Chest Pain, Week 28Chest Pain, Week 29Chest Pain, Week 30Chest Pain, Week 31Chest Pain, Week 32Chest Pain, Week 33Chest Pain, Week 34Chest Pain, Week 35Chest Pain, Week 36Chest Pain, Week 37Chest Pain, Week 38Chest Pain, Week 39Chest Pain, Week 40Chest Pain, Week 41Chest Pain, Week 42Chest Pain, Week 43Chest Pain, Week 44Chest Pain, Week 45Chest Pain, Week 46Chest Pain, Week 47Chest Pain, Week 48Chest Pain, Week 49Chest Pain, Week 50Chest Pain, Week 51Chest Pain, Week 52Chest Pain, Week 53Chest Pain, Week 54Chest Pain, Week 55Chest Pain, Week 56Chest Pain, Week 57Chest Pain, Week 58Chest Pain, Week 59Chest Pain, Week 60Chest Pain, Week 61Chest Pain, Week 62Chest Pain, Week 63Chest Pain, Week 64Chest Pain, Week 65Chest Pain, Week 66Chest Pain, Week 67Chest Pain, Week 68Chest Pain, Week 69Chest Pain, Week 70Chest Pain, Week 71Chest Pain, Week 72Chest Pain, Week 73Chest Pain, Week 74Chest Pain, Week 75Chest Pain, Week 76Chest Pain, Week 77Chest Pain, Week 78Chest Pain, Week 79Chest Pain, Week 80Chest Pain, Week 81Chest Pain, Week 82Chest Pain, Week 83Chest Pain, Week 84Chest Pain, Week 85Chest Pain, Week 86Chest Pain, Week 87Chest Pain, Week 88Chest Pain, Week 89Chest Pain, Week 90Chest Pain, Week 91Chest Pain, Week 92Chest Pain, Week 93Chest Pain, Week 94Chest Pain, Week 95Chest Pain, Week 96Chest Pain, Week 97Chest Pain, Week 98Chest Pain, Week 99Chest Pain, Week 100Chest Pain, Week 101Chest Pain, Week 102Chest Pain, Week 103Chest Pain, Week 104Chest Pain, Week 105Chest Pain, Week 106Chest Pain, Week 107Chest Pain, Week 108Chest Pain, Week 109Chest Pain, Week 110Chest Pain, Week 111Chest Pain, Week 112Chest Pain, Week 113Chest Pain, Week 114Chest Pain, Week 115Chest Pain, Week 116Chest Pain, Week 117Chest Pain, Week 118Chest Pain, Time of First PdChest Pain, Time of Last Tx DoseChest Pain, Survival Follow-Up Month 1Chest Pain, Survival Follow-Up Month 2Chest Pain, Survival Follow-Up Month 3Chest Pain, Survival Follow-Up Month 4Chest Pain, Survival Follow-Up Month 5Chest Pain, Survival Follow-Up Month 6Chest Pain, Survival Follow-Up Month 7Chest Pain, Survival Follow-Up Month 8Cough, Week 1Cough, Week 2Cough, Week 3Cough, Week 4Cough, Week 5Cough, Week 6Cough, Week 7Cough, Week 8Cough, Week 9Cough, Week 10Cough, Week 11Cough, Week 12Cough, Week 13Cough, Week 14Cough, Week 15Cough, Week 16Cough, Week 17Cough, Week 18Cough, Week 19Cough, Week 20Cough, Week 21Cough, Week 22Cough, Week 23Cough, Week 24Cough, Week 25Cough, Week 26Cough, Week 27Cough, Week 28Cough, Week 29Cough, Week 30Cough, Week 31Cough, Week 32Cough, Week 33Cough, Week 34Cough, Week 35Cough, Week 36Cough, Week 37Cough, Week 38Cough, Week 39Cough, Week 40Cough, Week 41Cough, Week 42Cough, Week 43Cough, Week 44Cough, Week 45Cough, Week 46Cough, Week 47Cough, Week 48Cough, Week 49Cough, Week 50Cough, Week 51Cough, Week 52Cough, Week 53Cough, Week 54Cough, Week 55Cough, Week 56Cough, Week 57Cough, Week 58Cough, Week 59Cough, Week 60Cough, Week 61Cough, Week 62Cough, Week 63Cough, Week 64Cough, Week 65Cough, Week 66Cough, Week 67Cough, Week 68Cough, Week 69Cough, Week 70Cough, Week 71Cough, Week 72Cough, Week 73Cough, Week 74Cough, Week 75Cough, Week 76Cough, Week 77Cough, Week 78Cough, Week 79Cough, Week 80Cough, Week 81Cough, Week 82Cough, Week 83Cough, Week 84Cough, Week 85Cough, Week 86Cough, Week 87Cough, Week 88Cough, Week 89Cough, Week 90Cough, Week 91Cough, Week 92Cough, Week 93Cough, Week 94Cough, Week 95Cough, Week 96Cough, Week 97Cough, Week 98Cough, Week 99Cough, Week 100Cough, Week 101Cough, Week 102Cough, Week 103Cough, Week 104Cough, Week 105Cough, Week 106Cough, Week 107Cough, Week 108Cough, Week 109Cough, Week 110Cough, Week 111Cough, Week 112Cough, Week 113Cough, Week 114Cough, Week 115Cough, Week 116Cough, Week 117Cough, Week 118Cough, Time of First PdCough, Time of Last Tx DoseCough, Survival Follow-Up Month 1Cough, Survival Follow-Up Month 2Cough, Survival Follow-Up Month 3Cough, Survival Follow-Up Month 4Cough, Survival Follow-Up Month 5Cough, Survival Follow-Up Month 6Cough, Survival Follow-Up Month 7Cough, Survival Follow-Up Month 8Dyspnoea, Week 1Dyspnoea, Week 2Dyspnoea, Week 3Dyspnoea, Week 4Dyspnoea, Week 5Dyspnoea, Week 6Dyspnoea, Week 7Dyspnoea, Week 8Dyspnoea, Week 9Dyspnoea, Week 10Dyspnoea, Week 11Dyspnoea, Week 12Dyspnoea, Week 13Dyspnoea, Week 14Dyspnoea, Week 15Dyspnoea, Week 16Dyspnoea, Week 17Dyspnoea, Week 18Dyspnoea, Week 19Dyspnoea, Week 20Dyspnoea, Week 21Dyspnoea, Week 22Dyspnoea, Week 23Dyspnoea, Week 24Dyspnoea, Week 25Dyspnoea, Week 26Dyspnoea, Week 27Dyspnoea, Week 28Dyspnoea, Week 29Dyspnoea, Week 30Dyspnoea, Week 31Dyspnoea, Week 32Dyspnoea, Week 33Dyspnoea, Week 34Dyspnoea, Week 35Dyspnoea, Week 36Dyspnoea, Week 37Dyspnoea, Week 38Dyspnoea, Week 39Dyspnoea, Week 40Dyspnoea, Week 41Dyspnoea, Week 42Dyspnoea, Week 43Dyspnoea, Week 44Dyspnoea, Week 45Dyspnoea, Week 46Dyspnoea, Week 47Dyspnoea, Week 48Dyspnoea, Week 49Dyspnoea, Week 50Dyspnoea, Week 51Dyspnoea, Week 52Dyspnoea, Week 53Dyspnoea, Week 54Dyspnoea, Week 55Dyspnoea, Week 56Dyspnoea, Week 57Dyspnoea, Week 58Dyspnoea, Week 59Dyspnoea, Week 60Dyspnoea, Week 61Dyspnoea, Week 62Dyspnoea, Week 63Dyspnoea, Week 64Dyspnoea, Week 65Dyspnoea, Week 66Dyspnoea, Week 67Dyspnoea, Week 68Dyspnoea, Week 69Dyspnoea, Week 70Dyspnoea, Week 71Dyspnoea, Week 72Dyspnoea, Week 73Dyspnoea, Week 74Dyspnoea, Week 75Dyspnoea, Week 76Dyspnoea, Week 77Dyspnoea, Week 78Dyspnoea, Week 79Dyspnoea, Week 80Dyspnoea, Week 81Dyspnoea, Week 82Dyspnoea, Week 83Dyspnoea, Week 84Dyspnoea, Week 85Dyspnoea, Week 86Dyspnoea, Week 87Dyspnoea, Week 88Dyspnoea, Week 89Dyspnoea, Week 90Dyspnoea, Week 91Dyspnoea, Week 92Dyspnoea, Week 93Dyspnoea, Week 94Dyspnoea, Week 95Dyspnoea, Week 96Dyspnoea, Week 97Dyspnoea, Week 98Dyspnoea, Week 99Dyspnoea, Week 100Dyspnoea, Week 101Dyspnoea, Week 102Dyspnoea, Week 103Dyspnoea, Week 104Dyspnoea, Week 105Dyspnoea, Week 106Dyspnoea, Week 107Dyspnoea, Week 108Dyspnoea, Week 109Dyspnoea, Week 110Dyspnoea, Week 111Dyspnoea, Week 112Dyspnoea, Week 113Dyspnoea, Week 114Dyspnoea, Week 115Dyspnoea, Week 116Dyspnoea, Week 117Dyspnoea, Week 118Dyspnoea, Time of First PdDyspnoea, Time of Last Tx DoseDyspnoea, Survival Follow-Up Month 1Dyspnoea, Survival Follow-Up Month 2Dyspnoea, Survival Follow-Up Month 3Dyspnoea, Survival Follow-Up Month 4Dyspnoea, Survival Follow-Up Month 5Dyspnoea, Survival Follow-Up Month 6Dyspnoea, Survival Follow-Up Month 7Dyspnoea, Survival Follow-Up Month 8
Arm C: Nab-Paclitaxel + Carboplatin0.04-0.08-0.14-0.19-0.17-0.35-0.38-0.35-0.36-0.20-0.27-0.34-0.31-0.32-0.45-0.28-0.32-0.28-0.18-0.23-0.37-0.27-0.29-0.43-0.25-0.50-0.35-0.22-0.30-0.15-0.49-0.29-0.29-0.15-0.26-0.24-0.27-0.19-0.060.060.14-0.100.13-0.080.150.000.18-0.08-0.230.000.550.150.180.080.210.050.050.130.000.090.610.05-0.440.190.250.42-0.500.080.700.300.080.250.420.430.250.000.000.070.080.140.250.070.000.001.131.331.000.830.670.671.170.881.500.670.671.171.170.830.671.251.171.00-0.500.250.500.000.250.25-0.500.000.250.500.00-0.25-0.25-0.50-0.250.00-0.19-0.180.03-0.10-0.09-0.13-0.02-0.220.33-0.750.01-0.02-0.09-0.26-0.18-0.27-0.27-0.26-0.32-0.28-0.31-0.30-0.23-0.31-0.39-0.19-0.18-0.26-0.29-0.29-0.36-0.25-0.26-0.28-0.28-0.41-0.27-0.34-0.38-0.29-0.46-0.17-0.31-0.03-0.14-0.05-0.080.020.000.100.07-0.04-0.02-0.050.100.030.100.00-0.120.230.050.120.210.080.290.140.100.060.180.140.00-0.050.190.130.080.08-0.300.000.200.20-0.170.000.000.070.080.000.250.000.000.210.080.430.300.201.001.170.830.670.831.000.671.001.000.830.830.831.000.500.831.000.830.670.500.500.500.500.250.250.500.500.750.500.500.250.500.750.750.50-0.15-0.31-0.030.03-0.18-0.09-0.04-0.171.33-0.500.180.130.060.170.210.170.200.260.230.370.400.440.400.420.360.450.550.460.480.370.510.500.440.250.270.200.310.240.300.300.340.280.390.320.350.320.240.310.390.380.450.370.480.220.320.360.320.320.460.410.710.600.700.710.820.690.740.800.780.670.910.580.580.630.800.700.520.630.961.000.700.570.670.740.700.670.730.570.570.600.500.570.280.160.701.330.400.400.530.270.330.750.400.670.530.330.670.730.470.500.400.400.700.500.400.300.600.600.800.600.300.501.000.500.500.400.401.000.380.430.560.710.670.570.660.631.070.10

[back to top]

Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population

TTD in Patient-reported Lung Cancer Symptoms Using EORTC QLQ-C30 Symptom Subscales in the ITT Population. The EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC scales and single-item measures will be linearly transformed so that each score has a range of 0-100. A high score for a functional scale represents a high or healthy level of functioning, and a high score for the global health status and HRQoL represents a high HRQoL; however, a high score for a symptom scale or item represents a high level of symptomatology or problems. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin3.2
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin4.2
Arm A: Atezolizumab + Paclitaxel + Carboplatin3.0

[back to top]

Progression Free Survival (PFS) as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in the Intent-to-Treat (ITT) Population

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the ITT population. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin5.6
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin6.5
Arm A: Atezolizumab + Paclitaxel + Carboplatin5.6

[back to top]

PFS as Determined by the Investigator Using RECIST v1.1 in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the Tumor Cell (TC) 2/3 or Tumor-Infiltrating Immune Cell (IC) 2/3 Population. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin5.6
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin8.4
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.0

[back to top]

PFS as Determined by the Investigator Using RECIST v1.1 in the TC1/2/3 or IC1/2/3 Population

PFS is defined as the time between the date of randomization and the date of first documented disease progression or death, whichever occurs first, in the TC1/2/3 or IC1/2/3 Population. (NCT02367794)
Timeframe: Up to approximately 30 months after first participant enrolled

InterventionMonths (Median)
Arm C: Nab-Paclitaxel + Carboplatin5.6
Arm B: Atezolizumab + Nab-Paclitaxel + Carboplatin7.1
Arm A: Atezolizumab + Paclitaxel + Carboplatin7.0

[back to top]

Phase I: Disease Assessment for Progression-Free Survival (PFS)

"To evaluate progression-free survival (PFS) and objective response for phase I participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions" (NCT02382406)
Timeframe: From date of registration to time of first documented progression or death, whichever occurs first (estimate 9 months)

Interventionmonths (Median)
Phase I, Cohort 15.2

[back to top]

Phase I: Overall Survival (OS)

To evaluate overall survival rates for phase I participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC. (NCT02382406)
Timeframe: From date of registration to date of death from any cause up to 49 months.

Interventionmonths (Median)
Phase I, Cohort 113

[back to top]

Phase II: Disease Assessment for Anti-Tumor Activity

To evaluate anti-tumor activity for phase I participants will be reported as a percentage change in the sum of the dimensions of all measurable lesions as defined by RECIST 1.1 criteria. (NCT02382406)
Timeframe: From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]).

Interventionpercent change (Median)
Phase II-46.7731

[back to top]

Phase II: Disease Assessment for Progression-Free Survival (PFS)

"To evaluate progression-free survival (PFS) for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria. PFS is defined as the duration of time from date of registration to time of progression or death, whichever occurs first.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions" (NCT02382406)
Timeframe: From date of registration to time of first documented progression or death, whichever occurs first (estimate 9 months)

Interventionmonths (Median)
Phase II6.2

[back to top]

Phase I: Disease Assessment for Anti-Tumor Activity

To evaluate anti-tumor activity for phase I participants will be reported as a percentage change in the sum of the dimensions of all measurable lesions as defined by RECIST 1.1 criteria. (NCT02382406)
Timeframe: From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]).

Interventionpercent change (Median)
Phase I, Cohort 1-6.9457

[back to top]

Phase II: Number of Participants With Adverse Events as a Measure of Safety and Tolerability

To evaluate the safety and tolerability of the combination of MK-3475 with carboplatin/nab-paclitaxel for the first line treatment of phase II participants with advanced NSCLC per CTCAE v4.0. Safety and tolerability is defined as rates of Grade 1-5 toxicity according to CTCAE v4. (NCT02382406)
Timeframe: Begin C1D1 and every 2 cycles (6 weeks) thereafter, for up to 2 years or until unacceptable toxicity.

InterventionParticipants (Count of Participants)
Patient had at least one adverse event of any grade.Patient had at least one grade 3 or greater adverse event.Patient had at least one grade 3 or greater treatment related adverse event.Patient having serious adverse event.
Phase II32312711

[back to top]

All Phases: Assessment of Association of PD-L1 Expression on PFS

To evaluate the association of PD-L1 expression on PFS for all participants receiving MK-3475. PD-L1 will be categorized as positive (≥50% expression) or negative (<50% expression) from pre-treatment and post-treatment biopsies. PFS will be summarized by PD-L1 expression. (NCT02382406)
Timeframe: From date of registration to time of first documented progression. (Measurable disease will be assessed after every 2 chemotherapy cycles [every 6 weeks thereafter for up to 2 years or until unacceptable toxicity]).

Interventionmonths (Median)
>=50%0-49%0%
Subjects With PD-L1 Staining Information4.64.25.6

[back to top]

Phase II: Overall Survival (OS)

To evaluate overall survival rates for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC. (NCT02382406)
Timeframe: From date of registration to date of death from any cause up to 42 months.

Interventionmonths (Median)
Phase II16

[back to top]

Phase II: Objective Response Rate

"To evaluate objective response rate for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria.~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR." (NCT02382406)
Timeframe: From the start of treatment until progression or death up to 24 months

InterventionParticipants (Count of Participants)
Phase II16

[back to top] [back to top]

Phase I : Objective Response Rate

"To evaluate objective response rate for phase II participants receiving MK-3475 and carboplatin/nab-paclitaxel for the first line treatment of advanced NSCLC per RECIST 1.1 criteria.~Objective response rate (ORR), is defined as the proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST)." (NCT02382406)
Timeframe: From the start of treatment until progression or death up to 11 months.

InterventionParticipants (Count of Participants)
Phase I, Cohort 11

[back to top]

Progression-free Survival (PFS) Time, as Assessed by the Investigator

PFS time was defined as the time in months from the date of randomization until first observation of PD (radiologically confirmed by Investigator), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Interventionmonths (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil5.5
Cisplatin/Carboplatin + 5-Flurouracil4.6

[back to top]

Duration of Response (DOR)

DOR was determined for participants whose BOR was either CR or PR. It was defined as the time from the first assessment of CR or PR until the event defining PFS time. PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

InterventionWeeks (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil18.1
Cisplatin/Carboplatin + 5-Flurouracil13.9

[back to top]

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Emergent Adverse Events Leading to Death and AEs Leading to Discontinuation

An Adverse event (AE) was defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug that were absent before treatment or that worsened relative to pre-treatment state up to 30 days after last administration. TEAEs included both Serious TEAEs and non-serious TEAEs. (NCT02383966)
Timeframe: Time from date of randomization up to data cutoff (assessed up to 904 days)

,
InterventionParticipants (Count of Participants)
TEAEsTESAEsTEAEs Leading to DeathAEs Leading to Discontinuation
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil163461127
Cisplatin/Carboplatin + 5-Flurouracil752188

[back to top]

Best Overall Response Rate (ORR)

The Best ORR was based on imaging and classified according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. The BOR rate was defined as the number of participants whose BOR was either complete response (CR) or partial response (PR), relative to the number of participants belonging to the trial set of interest. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Interventionpercentage of participants (Number)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil50
Cisplatin/Carboplatin + 5-Flurouracil26.6

[back to top]

Disease Control Rate (DCR)

The DCR was based on imaging and classified according to RECIST Version 1.1 criteria. The DCR was defined as the number of participants whose Best Overall Response is either CR, PR or stable disease (SD), divided by the number of participants belonging to the trial set of interest multiplied by 100. CR was defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must had reduction in short axis to less than (<) 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on trial. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Interventionpercentage of participants (Number)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil75.6
Cisplatin/Carboplatin + 5-Flurouracil59.5

[back to top]

Overall Survival (OS) Time

The OS time was defined as the time from randomization to the date of death. If a participant was alive at the time of analysis, survival time was censored at the last date when the participant was known to be alive. If this date was after data cut-off, participants were censored at the date of data cut-off. OS was measured using Kaplan-Meier (KM) estimates. (NCT02383966)
Timeframe: Time from date of randomization up to data cutoff (assessed up to 904 days)

Interventionmonths (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil10.2
Cisplatin/Carboplatin + 5-Flurouracil8.4

[back to top]

Progression-free Survival (PFS) Time, as Assessed by an Independent Review Committee (IRC)

PFS time was defined as the time in months from the date of randomization until first observation of PD (based on imaging as assessed by IRC), or death due to any cause when death occurs within 60 days after the last tumor assessment or randomization (whichever is later). PD is defined as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on trial; and/or unequivocal progression of existing non-target lesions and/or the presence of new lesions. The sum must also demonstrate an absolute increase of at least 5 millimeter. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02383966)
Timeframe: Every 6 weeks starting from the date of randomization until occurrence of PD, assessed up to data-cutoff (904 days)

Interventionmonths (Median)
Cetuximab + Cisplatin/Carboplatin + 5-Fluorouracil5.5
Cisplatin/Carboplatin + 5-Flurouracil4.2

[back to top]

Overall Survival (OS)

OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive. (NCT02392507)
Timeframe: From Date of Randomization until Death Due to Any Cause (Up to 18 Months)

InterventionMonths (Median)
Necitumumab + Nab-Paclitaxel + Carboplatin15.54

[back to top]

Percentage of Participants Who Achieve Best Overall Disease Response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD) (Disease Control Rate [DCR])

Disease Control Rate (DCR) was the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1 criteria. CR defined as the disappearance of all target and nontarget lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the LD of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. (NCT02392507)
Timeframe: From Date of Randomization to Objective Disease Progression or Start of New Anticancer Therapy (Up to 18 Months)

Interventionpercentage of participants (Number)
Necitumumab + Nab-Paclitaxel + Carboplatin78.4

[back to top]

PK: Maximum Concentration (Cmax) of Necitumumab, Nab-Paclitaxel, and Carboplatin

The Cmax is the maximum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin. (NCT02392507)
Timeframe: Cycle 1, 3 and 4: predose and <15minutes (min) post end-of-infusion

,,
Interventionng/mL (Geometric Mean)
Cycle 1Cycle 3Cycle 4
Carboplatin16.41610.5
Necitumumab231291277
Paclitaxel343284221

[back to top]

Pharmacokinetics (PK): Minimum Concentration (Cmin) of Necitumumab, Nab-Paclitaxel, and Carboplatin

The Cmin is the minimum observed serum/plasma concentration of Necitumumab, Nab-Paclitaxel, and Carboplatin. (NCT02392507)
Timeframe: Cycle 3 and cycle 4: predose

,,
Interventionnanogram per milliliter (ng/mL) (Geometric Mean)
Cycle 3Cycle 4
Carboplatin0.1310.209
Necitumumab65.290
Paclitaxel33.6107

[back to top]

Progression Free Survival (PFS)

PFS defined as time from date of randomization until first radiographic documentation of measured PD defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determined disease progression or death observed for participant.If participant was not known to have died or have objective progression as of data inclusion cutoff date for analysis,the PFS time censored at last adequate tumor assessment date.The use of new anticancer therapy prior to occurrence of PD resulted in censoring at the date of last radiographic assessment prior to initiation of new therapy. (NCT02392507)
Timeframe: From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up to 18 Months)

InterventionMonths (Median)
Necitumumab + Nab-Paclitaxel + Carboplatin5.59

[back to top]

Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR])

ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. Progressive disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. (NCT02392507)
Timeframe: From Date of Randomization to Objective Disease Progression (Up to 18 Months)

Interventionpercentage of participants (Number)
Necitumumab + Nab-Paclitaxel + Carboplatin51.0

[back to top]

Immunogenicity: Number of Participants Developing Anti-drug Antibodies to Necitumumab

A participant was considered to have an anti-drug antibody response if anti-drug antibodies (ADA) were detected at any time point. (NCT02392507)
Timeframe: Predose Cycle 1 Through Short Term Follow Up (Up To 18 Months)

InterventionParticipants (Count of Participants)
Necitumumab + Nab-Paclitaxel + Carboplatin3

[back to top]

OS in Participants With Blood Tumor Mutational Burden (bTMB)

OS is defined as the time from randomization to death from any cause. (NCT02409342)
Timeframe: From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)

,
InterventionMonths (Median)
bTMB >=10-WT PopulationbTMB >=16-WT PopulationbTMB >=20-WT Population
Atezolizumab11.213.917.2
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)10.38.510.5

[back to top]

OS in Participants With PD-L1 Expression

OS is defined as the time from randomization to death from any cause. (NCT02409342)
Timeframe: From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)

,
InterventionMonths (Median)
SP263 >=50%-WT PopulationSP263 >=25%-WT PopulationSP263 =1%-WT Population
Atezolizumab19.518.217.8
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)16.112.614.0

[back to top]

Overall Survival (OS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations

OS is defined as the time from randomization to death from any cause. (NCT02409342)
Timeframe: From randomization to death from any cause until data cut-off on 4 February 2020 (up to approximately 54.5 months)

,
InterventionMonths (Median)
TC2/3 or IC2/3-WT PopulationTC1/2/3 or IC1/2/3-WT Population
Atezolizumab19.918.9
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)16.114.7

[back to top]

Percentage of Participants Who Are Alive at 1 Year in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations

(NCT02409342)
Timeframe: Baseline to 1 year or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)

,
InterventionPercentage of participants (Number)
1-Year TC2/3 or IC2/3-WT Population1-Year TC1/2/3 or IC1/2/3-WT Population
Atezolizumab63.3959.95
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)58.6554.89

[back to top]

Percentage of Participants Who Are Alive at 2 Years in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations

(NCT02409342)
Timeframe: Baseline to 2 years or death, whichever occurs first until clinical cut-off date on 4 February 2020 (up to approximately 54.5 months)

,
InterventionPercentage of participants (Number)
2-Years TC2/3 or IC2/3-WT Population2-Years TC1/2/3 or IC1/2/3-WT Population
Atezolizumab44.1541.76
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)35.4230.82

[back to top]

Percentage of Participants With Anti-therapeutic Antibodies (ATAs)

(NCT02409342)
Timeframe: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionPercentage of participants (Number)
Baseline evaluable participantsPost-baseline evaluable participants
Atezolizumab1.424.3

[back to top]

Percentage of Participants With Objective Response (ORR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations

Objective response (partial response plus complete response) as determined by the investigator according to RECIST v1.1. (NCT02409342)
Timeframe: Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 4 Feb 2020 (up to approximately 54.5 months)

,
InterventionPercentage of participants (Number)
TC2/3 or IC2/3-WT PopulationTC1/2/3 or IC1/2/3-WT Population
Atezolizumab33.731.4
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)32.132.1

[back to top]

Progression-free Survival (PFS) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations

PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. PFS could not be formally tested. (NCT02409342)
Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months)

,
InterventionMonths (Number)
TC2/3 or IC2/3-WT PopulationTC1/2/3 or IC1/2/3-WT Population
Atezolizumab7.35.8
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)5.55.6

[back to top]

Time to Deterioration (TTD) in Patient-reported Lung Cancer Symptoms Score as Assessed by the Symptoms in Lung Cancer (SILC) Scale Symptom Score in the TC3 or IC3-WT Populations

TTD in each of the patient-reported lung cancer symptoms with use of the SILC scale. The SILC scale is a nine-item content valid self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a total symptom severity score. Each SILC symptom scale (dyspnea, cough, chest pain) score was calculated as the average of the component items (range 0 to 4). An increase in score suggested worsening in symptomatology. A symptom score change of 0.3 points for the dyspnea and cough scores was considered to be clinically significant; whereas a symptom score change of 0.5 points for the chest pain score was considered to be clinically significant. (NCT02409342)
Timeframe: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)

,
InterventionMonths (Median)
CoughDyspneaChest pain
Atezolizumab3.51.31.7
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)3.41.01.1

[back to top]

TTD as Assessed Using EORTC QLQ Supplementary Lung Cancer Module (EORTC QLQ-LC13) in the TC3 or IC3-WT Populations

TTD in patient-reported lung cancer symptoms, defined as time from randomization to deterioration (10-point change) in any of the following symptom subscales (cough, dyspnea [multi-item scale], and chest pain), whichever occurs first, as measured by the EORTC QLQ-LC13. EORTC QLQ-LC13 module incorporates one multi-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. (NCT02409342)
Timeframe: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)

,
InterventionMonths (Median)
CoughDyspneaChest pain
AtezolizumabNA11.1NA
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)NA11.8NA

[back to top]

Duration of Response (DOR) in the TC3 or IC3-WT Populations

DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. (NCT02409342)
Timeframe: From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionMonths (Number)
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)6.7
AtezolizumabNA

[back to top]

Maximum Observed Serum Concentration (Cmax) of Atezolizumab

(NCT02409342)
Timeframe: 0 hour (predose) and 30 minutes after atezolizumab infusion on Day 1 (infusion duration = up to 1 hour)

Interventionmicrograms per milliliter (μg/ mL) (Mean)
Atezolizumab411

[back to top]

Overall Survival (OS) in the TC3 or IC3-WT Populations

OS is defined as the time from randomization to death from any cause. (NCT02409342)
Timeframe: From randomization to death from any cause until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionMonths (Median)
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)13.1
Atezolizumab20.2

[back to top]

Percentage of Participants Who Are Alive at 1 Year in the TC3 or IC3-WT Populations

(NCT02409342)
Timeframe: Baseline to 1 year or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionPercentage of participants (Number)
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)50.64
Atezolizumab64.90

[back to top]

Percentage of Participants Who Are Alive at 2 Years in the TC3 or IC3-WT Populations

(NCT02409342)
Timeframe: Baseline to 2 years or death, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionPercentage of participants (Number)
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)24.79
Atezolizumab45.49

[back to top]

Percentage of Participants With at Least One Adverse Event

Percentage of participants with at least one adverse event. (NCT02409342)
Timeframe: Baseline up to until data cut-off on 8 March 2022 (up to approximately 79.5 months)

InterventionPercentage of participants (Number)
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)95.1
Atezolizumab92.3

[back to top]

Percentage of Participants With Objective Response (ORR) in the TC3 or IC3-WT Populations

Objective response (partial response plus complete response) as determined by the investigator according to RECIST v1.1. (NCT02409342)
Timeframe: Every 6 weeks for 48 weeks following Day 1, thereafter every 9 weeks after completion of Week 48 tumor assessment, regardless of treatment delays, until radiographic disease progression until data cut-off on 10 Sep 2018 (up to approximately 38 months)

InterventionPercentage of participants (Number)
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)28.6
Atezolizumab38.3

[back to top]

Progression-free Survival (PFS) in the TC3 or IC3-WT Populations

PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. PFS could not be formally tested. (NCT02409342)
Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionMonths (Number)
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)5.0
Atezolizumab8.1

[back to top]

Change From Baseline in Patient-reported Lung Cancer Symptoms Score as Assessed by the SILC Scale Symptom Score in the TC3 or IC3-WT Populations

Change from baseline in each of the patient-reported lung cancer symptoms with use of the SILC scale. The SILC scale is a nine-item content valid self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a total symptom severity score. Each SILC symptom scale (dyspnea, cough, chest pain) score was calculated as the average of the component items (range 0 to 4). An increase in score suggested worsening in symptomatology. A symptom score change of 0.3 points for the dyspnea and cough scores was considered to be clinically significant; whereas a symptom score change of 0.5 points for the chest pain score was considered to be clinically significant. (NCT02409342)
Timeframe: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionScore on a scale (Mean)
Chest Pain, Week 1Chest Pain, Week 2Chest Pain, Week 3Chest Pain, Week 4Chest Pain, Week 5Chest Pain, Week 6Chest Pain, Week 7Chest Pain, Week 8Chest Pain, Week 9Chest Pain, Week 10Chest Pain, Week 11Chest Pain, Week 12Chest Pain, Week 13Chest Pain, Week 14Chest Pain, Week 15Chest Pain, Week 16Chest Pain, Week 17Chest Pain, Week 18Chest Pain, Week 19Chest Pain, Week 20Chest Pain, Week 21Chest Pain, Week 22Chest Pain, Week 23Chest Pain, Week 24Chest Pain, Week 25Chest Pain, Week 26Chest Pain, Week 27Chest Pain, Week 28Chest Pain, Week 29Chest Pain, Week 30Chest Pain, Week 31Chest Pain, Week 32Chest Pain, Week 33Chest Pain, Week 34Chest Pain, Week 35Chest Pain, Week 36Chest Pain, Week 37Chest Pain, Week 38Chest Pain, Week 39Chest Pain, Week 40Chest Pain, Week 41Chest Pain, Week 42Chest Pain, Week 43Chest Pain, Week 44Chest Pain, Week 45Chest Pain, Week 46Chest Pain, Week 47Chest Pain, Week 48Chest Pain, Week 49Chest Pain, Week 50Chest Pain, Week 51Chest Pain, Week 52Chest Pain, Week 53Chest Pain, Week 54Chest Pain, Week 55Chest Pain, Week 56Chest Pain, Week 57Chest Pain, Week 58Chest Pain, Week 59Chest Pain, Week 60Chest Pain, Week 61Chest Pain, Week 62Chest Pain, Week 63Chest Pain, Week 64Chest Pain, Week 65Chest Pain, Week 66Chest Pain, Week 67Chest Pain, Week 68Chest Pain, Week 69Chest Pain, Week 70Chest Pain, Week 71Chest Pain, Week 72Chest Pain, Week 73Chest Pain, Week 74Chest Pain, Week 75Chest Pain, Week 76Chest Pain, Week 77Chest Pain, Week 78Chest Pain, Week 79Chest Pain, Week 80Chest Pain, Week 81Chest Pain, Week 82Chest Pain, Week 83Chest Pain, Week 84Chest Pain, Week 85Chest Pain, Week 86Chest Pain, Week 87Cough, Week 1Cough, Week 2Cough, Week 3Cough, Week 4Cough, Week 5Cough, Week 6Cough, Week 7Cough, Week 8Cough, Week 9Cough, Week 10Cough, Week 11Cough, Week 12Cough, Week 13Cough, Week 14Cough, Week 15Cough, Week 16Cough, Week 17Cough, Week 18Cough, Week 19Cough, Week 20Cough, Week 21Cough, Week 22Cough, Week 23Cough, Week 24Cough, Week 25Cough, Week 26Cough, Week 27Cough, Week 28Cough, Week 29Cough, Week 30Cough, Week 31Cough, Week 32Cough, Week 33Cough, Week 34Cough, Week 35Cough, Week 36Cough, Week 37Cough, Week 38Cough, Week 39Cough, Week 40Cough, Week 41Cough, Week 42Cough, Week 43Cough, Week 44Cough, Week 45Cough, Week 46Cough, Week 47Cough, Week 48Cough, Week 49Cough, Week 50Cough, Week 51Cough, Week 52Cough, Week 53Cough, Week 54Cough, Week 55Cough, Week 56Cough, Week 57Cough, Week 58Cough, Week 59Cough, Week 60Cough, Week 61Cough, Week 62Cough, Week 63Cough, Week 64Cough, Week 65Cough, Week 66Cough, Week 67Cough, Week 68Cough, Week 69Cough, Week 70Cough, Week 71Cough, Week 72Cough, Week 73Cough, Week 74Cough, Week 75Cough, Week 76Cough, Week 77Cough, Week 78Cough, Week 79Cough, Week 80Cough, Week 81Cough, Week 82Cough, Week 83Cough, Week 84Cough, Week 85Cough, Week 86Cough, Week 87Dyspnoea, Week 1Dyspnoea, Week 2Dyspnoea, Week 3Dyspnoea, Week 4Dyspnoea, Week 5Dyspnoea, Week 6Dyspnoea, Week 7Dyspnoea, Week 8Dyspnoea, Week 9Dyspnoea, Week 10Dyspnoea, Week 11Dyspnoea, Week 12Dyspnoea, Week 13Dyspnoea, Week 14Dyspnoea, Week 15Dyspnoea, Week 16Dyspnoea, Week 17Dyspnoea, Week 18Dyspnoea, Week 19Dyspnoea, Week 20Dyspnoea, Week 21Dyspnoea, Week 22Dyspnoea, Week 23Dyspnoea, Week 24Dyspnoea, Week 25Dyspnoea, Week 26Dyspnoea, Week 27Dyspnoea, Week 28Dyspnoea, Week 29Dyspnoea, Week 30Dyspnoea, Week 31Dyspnoea, Week 32Dyspnoea, Week 33Dyspnoea, Week 34Dyspnoea, Week 35Dyspnoea, Week 36Dyspnoea, Week 37Dyspnoea, Week 38Dyspnoea, Week 39Dyspnoea, Week 40Dyspnoea, Week 41Dyspnoea, Week 42Dyspnoea, Week 43Dyspnoea, Week 44Dyspnoea, Week 45Dyspnoea, Week 46Dyspnoea, Week 47Dyspnoea, Week 48Dyspnoea, Week 49Dyspnoea, Week 50Dyspnoea, Week 51Dyspnoea, Week 52Dyspnoea, Week 53Dyspnoea, Week 54Dyspnoea, Week 55Dyspnoea, Week 56Dyspnoea, Week 57Dyspnoea, Week 58Dyspnoea, Week 59Dyspnoea, Week 60Dyspnoea, Week 61Dyspnoea, Week 62Dyspnoea, Week 63Dyspnoea, Week 64Dyspnoea, Week 65Dyspnoea, Week 66Dyspnoea, Week 67Dyspnoea, Week 68Dyspnoea, Week 69Dyspnoea, Week 70Dyspnoea, Week 71Dyspnoea, Week 72Dyspnoea, Week 73Dyspnoea, Week 74Dyspnoea, Week 75Dyspnoea, Week 76Dyspnoea, Week 77Dyspnoea, Week 78Dyspnoea, Week 79Dyspnoea, Week 80Dyspnoea, Week 81Dyspnoea, Week 82Dyspnoea, Week 83Dyspnoea, Week 84Dyspnoea, Week 85Dyspnoea, Week 86Dyspnoea, Week 87
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)0.570.420.250.150.270.300.230.170.270.300.260.220.070.070.100.000.220.110.110.200.030.300.00-0.090.270.120.050.00-0.250.210.180.410.000.400.000.060.310.230.220.430.360.250.300.140.630.300.500.501.000.800.880.750.701.131.170.380.671.171.000.501.000.830.500.000.000.001.000.750.501.000.501.001.500.500.750.500.501.000.500.750.750.000.000.500.000.000.000.13-0.01-0.03-0.02-0.01-0.18-0.20-0.10-0.24-0.070.02-0.08-0.09-0.20-0.05-0.10-0.040.02-0.230.00-0.17-0.20-0.22-0.13-0.45-0.46-0.50-0.45-0.50-0.88-0.86-0.73-0.77-0.80-0.14-0.17-0.250.05-0.50-0.360.210.170.100.360.250.100.500.170.670.300.130.630.700.500.670.500.500.670.330.750.500.330.000.000.500.000.250.250.250.250.00-0.500.000.000.000.250.000.250.000.250.250.000.000.500.000.000.000.420.330.250.430.550.500.630.500.460.430.360.390.430.260.360.180.480.390.290.600.270.550.340.360.220.320.350.350.200.180.180.220.200.160.110.110.280.400.270.570.310.300.400.490.650.560.300.601.400.241.051.100.761.101.000.400.530.800.601.200.730.670.300.200.600.400.500.200.300.300.100.000.000.200.300.300.400.300.100.500.400.600.600.800.600.400.40

[back to top]

Change From Baseline in Patient-reported Lung Cancer Symptoms Score as Assessed by the SILC Scale Symptom Score in the TC3 or IC3-WT Populations

Change from baseline in each of the patient-reported lung cancer symptoms with use of the SILC scale. The SILC scale is a nine-item content valid self-report measure of lung cancer symptoms. It measures severity of cough, dyspnea, and chest pain with a total symptom severity score. Each SILC symptom scale (dyspnea, cough, chest pain) score was calculated as the average of the component items (range 0 to 4). An increase in score suggested worsening in symptomatology. A symptom score change of 0.3 points for the dyspnea and cough scores was considered to be clinically significant; whereas a symptom score change of 0.5 points for the chest pain score was considered to be clinically significant. (NCT02409342)
Timeframe: Baseline until data cut-off on 10 September 2018 (up to approximately 38 months)

InterventionScore on a scale (Mean)
Chest Pain, Week 1Chest Pain, Week 2Chest Pain, Week 3Chest Pain, Week 4Chest Pain, Week 5Chest Pain, Week 6Chest Pain, Week 7Chest Pain, Week 8Chest Pain, Week 9Chest Pain, Week 10Chest Pain, Week 11Chest Pain, Week 12Chest Pain, Week 13Chest Pain, Week 14Chest Pain, Week 15Chest Pain, Week 16Chest Pain, Week 17Chest Pain, Week 18Chest Pain, Week 19Chest Pain, Week 20Chest Pain, Week 21Chest Pain, Week 22Chest Pain, Week 23Chest Pain, Week 24Chest Pain, Week 25Chest Pain, Week 26Chest Pain, Week 27Chest Pain, Week 28Chest Pain, Week 29Chest Pain, Week 30Chest Pain, Week 31Chest Pain, Week 32Chest Pain, Week 33Chest Pain, Week 34Chest Pain, Week 35Chest Pain, Week 36Chest Pain, Week 37Chest Pain, Week 38Chest Pain, Week 39Chest Pain, Week 40Chest Pain, Week 41Chest Pain, Week 42Chest Pain, Week 43Chest Pain, Week 44Chest Pain, Week 45Chest Pain, Week 46Chest Pain, Week 47Chest Pain, Week 48Chest Pain, Week 49Chest Pain, Week 50Chest Pain, Week 51Chest Pain, Week 52Chest Pain, Week 53Chest Pain, Week 54Chest Pain, Week 55Chest Pain, Week 56Chest Pain, Week 57Chest Pain, Week 58Chest Pain, Week 59Chest Pain, Week 60Chest Pain, Week 61Chest Pain, Week 62Chest Pain, Week 63Chest Pain, Week 64Chest Pain, Week 65Chest Pain, Week 66Chest Pain, Week 67Chest Pain, Week 68Chest Pain, Week 69Chest Pain, Week 70Chest Pain, Week 71Chest Pain, Week 72Chest Pain, Week 73Chest Pain, Week 74Chest Pain, Week 75Chest Pain, Week 76Chest Pain, Week 77Chest Pain, Week 78Chest Pain, Week 79Chest Pain, Week 80Chest Pain, Week 81Chest Pain, Week 82Chest Pain, Week 83Chest Pain, Week 84Chest Pain, Week 85Chest Pain, Week 86Chest Pain, Week 87Chest Pain, Week 88Chest Pain, Week 89Chest Pain, Week 90Chest Pain, Week 91Chest Pain, Week 92Chest Pain, Week 93Chest Pain, Week 94Chest Pain, Week 95Chest Pain, Week 96Chest Pain, Week 97Chest Pain, Week 98Chest Pain, Week 99Chest Pain, Week 100Chest Pain, Week 101Chest Pain, Week 102Chest Pain, Week 103Chest Pain, Week 104Chest Pain, Week 105Chest Pain, Week 106Chest Pain, Week 107Chest Pain, Week 108Chest Pain, Week 109Chest Pain, Week 110Chest Pain, Week 111Chest Pain, Week 112Chest Pain, Week 113Chest Pain, Week 114Chest Pain, Week 115Chest Pain, Week 116Chest Pain, Week 117Chest Pain, Week 118Chest Pain, Week 119Chest Pain, Week 120Chest Pain, Week 121Chest Pain, Week 122Chest Pain, Week 123Chest Pain, Week 124Chest Pain, Week 125Chest Pain, Week 126Chest Pain, Week 127Chest Pain, Week 128Chest Pain, Week 129Chest Pain, Week 130Chest Pain, Week 131Cough, Week 1Cough, Week 2Cough, Week 3Cough, Week 4Cough, Week 5Cough, Week 6Cough, Week 7Cough, Week 8Cough, Week 9Cough, Week 10Cough, Week 11Cough, Week 12Cough, Week 13Cough, Week 14Cough, Week 15Cough, Week 16Cough, Week 17Cough, Week 18Cough, Week 19Cough, Week 20Cough, Week 21Cough, Week 22Cough, Week 23Cough, Week 24Cough, Week 25Cough, Week 26Cough, Week 27Cough, Week 28Cough, Week 29Cough, Week 30Cough, Week 31Cough, Week 32Cough, Week 33Cough, Week 34Cough, Week 35Cough, Week 36Cough, Week 37Cough, Week 38Cough, Week 39Cough, Week 40Cough, Week 41Cough, Week 42Cough, Week 43Cough, Week 44Cough, Week 45Cough, Week 46Cough, Week 47Cough, Week 48Cough, Week 49Cough, Week 50Cough, Week 51Cough, Week 52Cough, Week 53Cough, Week 54Cough, Week 55Cough, Week 56Cough, Week 57Cough, Week 58Cough, Week 59Cough, Week 60Cough, Week 61Cough, Week 62Cough, Week 63Cough, Week 64Cough, Week 65Cough, Week 66Cough, Week 67Cough, Week 68Cough, Week 69Cough, Week 70Cough, Week 71Cough, Week 72Cough, Week 73Cough, Week 74Cough, Week 75Cough, Week 76Cough, Week 77Cough, Week 78Cough, Week 79Cough, Week 80Cough, Week 81Cough, Week 82Cough, Week 83Cough, Week 84Cough, Week 85Cough, Week 86Cough, Week 87Cough, Week 88Cough, Week 89Cough, Week 90Cough, Week 91Cough, Week 92Cough, Week 93Cough, Week 94Cough, Week 95Cough, Week 96Cough, Week 97Cough, Week 98Cough, Week 99Cough, Week 100Cough, Week 101Cough, Week 102Cough, Week 103Cough, Week 104Cough, Week 105Cough, Week 106Cough, Week 107Cough, Week 108Cough, Week 109Cough, Week 110Cough, Week 111Cough, Week 112Cough, Week 113Cough, Week 114Cough, Week 115Cough, Week 116Cough, Week 117Cough, Week 118Cough, Week 119Cough, Week 120Cough, Week 121Cough, Week 122Cough, Week 123Cough, Week 124Cough, Week 125Cough, Week 126Cough, Week 127Cough, Week 128Cough, Week 129Cough, Week 130Cough, Week 131Dyspnoea, Week 1Dyspnoea, Week 2Dyspnoea, Week 3Dyspnoea, Week 4Dyspnoea, Week 5Dyspnoea, Week 6Dyspnoea, Week 7Dyspnoea, Week 8Dyspnoea, Week 9Dyspnoea, Week 10Dyspnoea, Week 11Dyspnoea, Week 12Dyspnoea, Week 13Dyspnoea, Week 14Dyspnoea, Week 15Dyspnoea, Week 16Dyspnoea, Week 17Dyspnoea, Week 18Dyspnoea, Week 19Dyspnoea, Week 20Dyspnoea, Week 21Dyspnoea, Week 22Dyspnoea, Week 23Dyspnoea, Week 24Dyspnoea, Week 25Dyspnoea, Week 26Dyspnoea, Week 27Dyspnoea, Week 28Dyspnoea, Week 29Dyspnoea, Week 30Dyspnoea, Week 31Dyspnoea, Week 32Dyspnoea, Week 33Dyspnoea, Week 34Dyspnoea, Week 35Dyspnoea, Week 36Dyspnoea, Week 37Dyspnoea, Week 38Dyspnoea, Week 39Dyspnoea, Week 40Dyspnoea, Week 41Dyspnoea, Week 42Dyspnoea, Week 43Dyspnoea, Week 44Dyspnoea, Week 45Dyspnoea, Week 46Dyspnoea, Week 47Dyspnoea, Week 48Dyspnoea, Week 49Dyspnoea, Week 50Dyspnoea, Week 51Dyspnoea, Week 52Dyspnoea, Week 53Dyspnoea, Week 54Dyspnoea, Week 55Dyspnoea, Week 56Dyspnoea, Week 57Dyspnoea, Week 58Dyspnoea, Week 59Dyspnoea, Week 60Dyspnoea, Week 61Dyspnoea, Week 62Dyspnoea, Week 63Dyspnoea, Week 64Dyspnoea, Week 65Dyspnoea, Week 66Dyspnoea, Week 67Dyspnoea, Week 68Dyspnoea, Week 69Dyspnoea, Week 70Dyspnoea, Week 71Dyspnoea, Week 72Dyspnoea, Week 73Dyspnoea, Week 74Dyspnoea, Week 75Dyspnoea, Week 76Dyspnoea, Week 77Dyspnoea, Week 78Dyspnoea, Week 79Dyspnoea, Week 80Dyspnoea, Week 81Dyspnoea, Week 82Dyspnoea, Week 83Dyspnoea, Week 84Dyspnoea, Week 85Dyspnoea, Week 86Dyspnoea, Week 87Dyspnoea, Week 88Dyspnoea, Week 89Dyspnoea, Week 90Dyspnoea, Week 91Dyspnoea, Week 92Dyspnoea, Week 93Dyspnoea, Week 94Dyspnoea, Week 95Dyspnoea, Week 96Dyspnoea, Week 97Dyspnoea, Week 98Dyspnoea, Week 99Dyspnoea, Week 100Dyspnoea, Week 101Dyspnoea, Week 102Dyspnoea, Week 103Dyspnoea, Week 104Dyspnoea, Week 105Dyspnoea, Week 106Dyspnoea, Week 107Dyspnoea, Week 108Dyspnoea, Week 109Dyspnoea, Week 110Dyspnoea, Week 111Dyspnoea, Week 112Dyspnoea, Week 113Dyspnoea, Week 114Dyspnoea, Week 115Dyspnoea, Week 116Dyspnoea, Week 117Dyspnoea, Week 118Dyspnoea, Week 119Dyspnoea, Week 120Dyspnoea, Week 121Dyspnoea, Week 122Dyspnoea, Week 123Dyspnoea, Week 124Dyspnoea, Week 125Dyspnoea, Week 126Dyspnoea, Week 127Dyspnoea, Week 128Dyspnoea, Week 129Dyspnoea, Week 130Dyspnoea, Week 131
Atezolizumab0.310.330.430.430.280.250.300.200.330.250.210.330.300.270.450.190.220.260.230.230.110.190.330.180.290.110.200.230.180.320.330.350.040.310.280.080.390.310.140.300.300.330.180.420.310.370.310.170.470.200.310.540.290.250.150.290.080.190.000.380.360.430.290.400.350.45-0.090.390.500.180.450.420.270.500.330.000.190.210.310.720.080.080.500.430.380.210.290.43-0.200.07-0.070.330.500.200.330.330.500.330.880.500.830.500.631.001.000.501.001.501.752.001.501.501.502.001.752.002.002.001.752.502.003.002.503.003.003.002.003.003.002.002.000.100.19-0.01-0.030.00-0.18-0.06-0.13-0.06-0.10-0.07-0.09-0.20-0.07-0.19-0.19-0.21-0.26-0.27-0.33-0.19-0.170.05-0.120.14-0.03-0.050.080.050.120.05-0.04-0.29-0.02-0.09-0.36-0.04-0.07-0.20-0.390.05-0.200.03-0.11-0.260.08-0.030.230.260.000.060.270.380.070.120.140.150.080.06-0.040.000.14-0.040.350.120.45-0.090.610.500.230.550.420.640.560.670.310.560.360.630.330.580.250.670.290.380.570.640.640.500.430.500.670.790.300.670.580.570.670.250.600.500.500.250.000.33-0.500.000.000.500.500.500.000.500.500.500.500.500.500.502.002.002.002.002.002.002.002.002.002.002.002.000.120.290.250.280.210.210.320.250.340.490.240.350.230.260.390.260.160.210.330.230.400.220.380.420.500.280.370.450.380.540.410.580.360.280.27-0.020.420.500.250.440.530.520.410.310.530.370.390.390.470.530.590.720.400.630.720.610.450.600.180.570.540.660.770.660.940.670.330.820.740.750.840.800.670.890.710.530.650.400.550.690.530.530.870.890.830.660.661.200.560.740.510.871.200.480.871.131.260.800.700.881.130.960.551.071.070.401.131.501.301.501.601.501.501.601.401.301.501.301.502.202.402.202.202.202.202.202.202.202.202.202.20

[back to top]

Duration of Response (DOR) in the TC2/3 or IC2/3-WT and TC1/2/3 or IC1/2/3-WT Populations

DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression, as determined by the investigator with use of RECIST v1.1, or death from any cause, whichever occurs first. (NCT02409342)
Timeframe: From first occurrence of a complete response or partial response, whichever occurs first, until first date that progressive disease or death is documented, whichever occurs first until data cut-off on 4 February 2020 (up to approximately 54.5 months)

,
InterventionMonths (Number)
TC2/3 or IC2/3-WT PopulationTC1/2/3 or IC1/2/3-WT Population
Atezolizumab38.926.3
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)5.85.7

[back to top]

Investigator-Assessed PFS in Participants With bTMB According to RECIST v1.1

PFS according to RECIST v1.1 in the bTMB subpopulations. (NCT02409342)
Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)

,
InterventionMonths (Median)
bTMB >=10-WT PopulationbTMB >=16-WT PopulationbTMB >=20-WT Population
Atezolizumab5.56.86.8
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)4.34.45.2

[back to top]

Investigator-Assessed PFS in Participants With PD-L1 Expression According to RECIST v1.1

Investigator-assessed PFS according to RECIST v1.1 in the PD-L1 (defined with SP263 IHC assay) (NCT02409342)
Timeframe: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first until data cut-off on 10 September 2018 (up to approximately 38 months)

,
InterventionMonths (Median)
SP263 >=50%-WT PopulationSP263 >=25%-WT PopulationSP263 >=1%-WT Population
Atezolizumab7.06.96.8
Chemotherapy (Carboplatin/ Cisplatin) + (Pemetrexed/ Gemcitabine)4.94.95.4

[back to top]

Minimum Observed Serum Concentration (Cmin) of Atezolizumab

(NCT02409342)
Timeframe: Prior to infusion (0 hour) on Day 1 of Cycles 2, 3, 4, 8, 16, and every eighth cycle thereafter, and at treatment discontinuation until data cut-off on 10 September 2018 (up to approximately 38 months) (cycle duration = 21 days)

Interventionmicrograms per milliliter (μg/ mL) (Mean)
Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 8 Day 1Cycle 16 Day 1Cycle 24 Day 1Cycle 32 Day 1Cycle 40 Day 1Cycle 48 Day 1Treatment Discontinuation Visit
Atezolizumab76.7121154201213245276252555121

[back to top]

Overall Survival

Overall survival (OS) was defined as the time from the participant's first dose of study drug to the date of death, and was calculated using Kaplan-Meier methods. Participants who did not die were censored at the date of last study visit or the last known date to be alive, whichever was later. (NCT02412371)
Timeframe: From first dose of study drug until end of study; maximum time on follow-up was approximately 46 months.

Interventionmonths (Median)
Total32.6

[back to top]

Duration of Overall Response (DOR)

Duration of overall response was defined as time from the date of first response (CR or PR) to the earliest documentation of radiographic progressive disease or death due to disease progression, calculated using Kaplan-Meier methods. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment. (NCT02412371)
Timeframe: Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.

Interventionmonths (Median)
Total30.4

[back to top]

Number of Participants With Dose-limiting Toxicities (DLTs)

"DLTs were defined as the following events considered treatment-related by the Investigator, graded per Common Terminology Criteria for Adverse Events (CTCAE) v4.0.~Radiation-induced myelopathy/myelitis or ≥ Grade (G) 3 cardiac toxicity~Radiation-related pneumonitis resulting in delay in RT, CT, or veliparib of >3 weeks or early discontinuation (DC) of RT (total dose <50 Gy)~≥G4 esophagitis or esophagitis, dysphagia, and odynophagia requiring treatment interruption of >7 days despite medical management, neutropenia for >7 days or neutropenic fever or thrombocytopenia~≥G2 seizure~G4 diarrhea or nausea/vomiting despite antiemetic therapy for >48 hours~Any other toxicity resulting in delay in RT, CT or veliparib >14 days or early DC of RT~Other nonhematologic toxicities ≥G3, except anorexia, fatigue, G3 infection, G3 aspartate/alanine transferase (AST/ALT) elevations ≤7 days, infusion reactions, G3/4 lymphopenia or electrolyte abnormalities corrected to ≤G2 in <48 hours" (NCT02412371)
Timeframe: For Cohorts 1 - 5, from the start of veliparib dosing through 28 days after RT completion or until initiation of consolidation CT, approx. 10 weeks; For Cohort 6, 21 days from start of consolidation CT or until the start of cycle 2 consolidation therapy.

InterventionParticipants (Count of Participants)
Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT1
Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT0
Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT2

[back to top]

Objective Response Rate

"Objective response rate (ORR) is defined as the percentage of participants who have a confirmed complete response (CR) or partial response (PR) as assessed by the investigator using RECIST v1.1. Participants who did not meet complete response or partial response, including those who did not have post-baseline radiological assessments were considered as non-responders.~Complete Response (CR): The disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. Normalization of tumor marker level. All lymph nodes must be non-pathological in size (< 10 mm short axis).~Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~Response must have been confirmed 4 weeks after the first documentation." (NCT02412371)
Timeframe: Tumor assessments were performed prior to consolidation chemotherapy, 24 weeks after start of treatment, every 8 weeks until 1 year after start of treatment, and then every 12 weeks until disease progression; median time on follow-up was 11 months.

Interventionpercentage of participants (Number)
Veliparib 60 mg BID + CRT -> Veliparib 120 mg BID + CT50.0
Veliparib 80 mg BID + CRT -> Veliparib 120 mg BID + CT50.0
Veliparib 120 mg BID + CRT -> Veliparib 120 mg BID + CT100.0
Veliparib 200 mg BID + CRT -> Veliparib 120 mg BID + CT62.5
Veliparib 240 mg BID + CRT -> Veliparib 120 mg BID + CT72.7
Veliparib 240 mg BID + CRT -> Veliparib 240 mg BID + CT0.0

[back to top]

Progression-free Survival

"Progression-free survival (PFS) was defined as the time from first dose of study drug to the date of earliest radiographic disease progression per investigator assessment based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or death, and was calculated using Kaplan-Meier methods. All radiographic disease progression was included regardless whether the event occurred while the participant was taking study drug or had previously discontinued study drug. Participants who did not experience radiographic disease progression or death were censored at the date of the last disease assessment. Participants with no post-baseline disease assessment were censored at first dose date plus 1 day.~Progressive disease (PD) was defined as at least a 20% increase in the size of target lesions with an absolute increase of at least 5 mm, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions." (NCT02412371)
Timeframe: From first dose until end of study; maximum time on follow-up was approximately 46 months.

Interventionmonths (Median)
Total19.6

[back to top]

Event-free Survival

Event-free survival is defined as the time from registration to the earliest occurrence of recurrence of any type, disease progression, new invasive primary cancer, or death from any cause. Disease progression will be assessed using RECIST 1.1. Disease progression is defined as appearance of one or more new lesions, unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT02412670)
Timeframe: Assessed every 3 months for 2 years, and every 6 months for 3-5 years

Interventionmonths (Median)
Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)NA
Arm B (Gemcitabine, Carboplatin)10.2

[back to top]

Proportion of Patients With Renal Insufficiency at Completion of Chemotherapy

Renal insufficiency is defined as CrCl < 60 ml/min. (NCT02412670)
Timeframe: Assessed at completion of chemotherapy; at 8 weeks for Arm A and 12 weeks for Arm B

Interventionproportion of participants (Number)
Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)0.2
Arm B (Gemcitabine, Carboplatin)0.833

[back to top]

Recurrence-free Survival

Recurrence-free survival is defined as the time from the date of surgery to disease recurrence or death from any cause. Patients alive without documented recurrence will be censored at the date of last disease assessment. (NCT02412670)
Timeframe: Assessed every 3 months for 2 years; and every 6 months for 3-5 years

Interventionmonths (Median)
Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)NA
Arm B (Gemcitabine, Carboplatin)8.5

[back to top]

Proportion of Patients With Renal Insufficiency at Completion of Surgery

Renal insufficiency is defined as CrCl < 60 ml/min. (NCT02412670)
Timeframe: Assessed at completion of surgery (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)

Interventionproportion of participants (Number)
Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)0.69
Arm B (Gemcitabine, Carboplatin)0.833

[back to top]

Bladder Cancer-free Survival

Bladder cancer-free survival was defined as the time from the date of surgery to the earlier of a return of bladder cancer or death from any cause. Patients alive without documented bladder cancer were censored at the date of last disease assessment. (NCT02412670)
Timeframe: Assessed every 3 months for 2 years, and every 6 months for 3-5 years

Interventionmonths (Median)
Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)NA
Arm B (Gemcitabine, Carboplatin)NA

[back to top]

Complete Pathologic Response Rate

Complete pathologic response is defined as pT0pN0 (no evidence of disease) as assessed by pathologic evaluation of nephrectomy/ureterectomy and any identifiable regional lymph nodes. (NCT02412670)
Timeframe: Assessed at nephroureterectomy or regional lymph node dissection (21-60 days from completion of chemotherapy; chemotherapy was administered for a total of 4 cycles; cycle length is 14 days and 21 days for arms A and B, respectively)

Interventionproportion of participants (Number)
Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)0.103
Arm B (Gemcitabine, Carboplatin)0.167

[back to top]

Cumulative Incidence of Cancer-specific Death at 24 Months

Cancer-specific survival was defined as the time from registration to death due to cancer; deaths due to other causes are counted as competing events. Cancer-specific survival was analyzed using Gray's method and cumulative incidence of cancer-specific death at 24 months is reported. (NCT02412670)
Timeframe: Assessed every 3 months for 2 years

Interventionproportion of patients died of cancer (Number)
Arm A (Methotrexate, Vinblastine, Doxorubicin, Cisplatin)0.09
Arm B (Gemcitabine, Carboplatin)0.20

[back to top]

Number of Participants With Minimal Residual Disease

To evaluate minimal residual disease rates (residual cancer burden 0+1) with two neoadjuvant chemotherapy regimens in subjects with stage I-III triple-negative breast cancer. (NCT02413320)
Timeframe: 20 weeks

InterventionParticipants (Count of Participants)
Carboplatin + Paclitaxel Then Doxorubicin + Cyclophosphamide31
Carboplatin + Docetaxel35

[back to top]

Number of Participants With Pathological Complete Response

To evaluate the pathological complete response rates with neoadjuvant chemotherapy regimens of carboplatin plus paclitaxel x 4 cycles followed by doxorubicin plus cyclophosphamide X 4 cycles and carboplatin plus docetaxel X 6 cycles in subjects with stage I-III triple-negative breast cancer. Pathological complete response is defined as no evidence of disease in the breast and axilla at the time of pathology review except for DCIS. (NCT02413320)
Timeframe: 20 weeks

InterventionParticipants (Count of Participants)
Carboplatin + Paclitaxel Then Doxorubicin + Cyclophosphamide26
Carboplatin + Docetaxel28

[back to top]

Percentage of Participants With Adverse Events

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with the treatment. An adverse event was therefore any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsened during the study were also considered as adverse events. (NCT02419742)
Timeframe: Baseline up to approximately 5 years and 10 months

InterventionParticipants (Count of Participants)
Trastuzumab With AC-TH Regimen46
Trastuzumab With TCH Regimen51

[back to top]

Overall Survival (OS)

Overall survival was defined as time from the date of first study treatment until date of death, regardless of the cause of death. (NCT02419742)
Timeframe: Time from the date of first study treatment until date of death, regardless of the cause of death within 12 months from the last dose of Trastuzumab for every participant. The follow up period was 52 weeks from the last dose of treatment in both arms.

InterventionMonths (Median)
Trastuzumab With AC-TH RegimenNA
Trastuzumab With TCH RegimenNA

[back to top]

Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography

LVEF assessments were performed every three months (four cycles) using echocardiogram (NCT02419742)
Timeframe: Baseline to every 4 cycles up to Cycle 21 (AC-TH), every 4 cycles up to Cycle 17 (TCH) (each cycle is 21 days), at study treatment completion (12 months post baseline) at 6 month (18 months post baseline) and 12 month follow-up (24 months post baseline)

InterventionPercentage of LVEF (Mean)
BaselineCycle 5Cycle 9Cycle 13Cycle 17Cycle 21Study Completion Visit6 Month Follow Up12 Month Follow Up
Trastuzumab With AC-TH Regimen60.1-0.2-0.5-2.0-1.8-1.8-3.3-1.6-2.2

[back to top]

Clinically Significant Changes in Cardiac Function As Determined by Left Ventricular Ejection Fraction (LVEF) Measurements Using Echocardiography

LVEF assessments were performed every three months (four cycles) using echocardiogram (NCT02419742)
Timeframe: Baseline to every 4 cycles up to Cycle 21 (AC-TH), every 4 cycles up to Cycle 17 (TCH) (each cycle is 21 days), at study treatment completion (12 months post baseline) at 6 month (18 months post baseline) and 12 month follow-up (24 months post baseline)

InterventionPercentage of LVEF (Mean)
BaselineCycle 5Cycle 9Cycle 13Cycle 17Study Completion Visit6 Month Follow Up12 Month Follow Up
Trastuzumab With TCH Regimen62.1-0.4-1.0-1.0-1.1-0.7-0.3-0.4

[back to top]

Disease Free Survival (DFS)

DFS was defined as time from the date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause. Local, regional or distant recurrence, and contra-lateral breast cancer was assessed by combination of physical examination, mammography and pelvic examination. (NCT02419742)
Timeframe: The date of first study treatment to the date of local, regional or distant recurrence, contra-lateral breast cancer or death due to any cause within 12 months from the last dose of Trastuzumab for every participant

InterventionMonths (Median)
Trastuzumab With AC-TH RegimenNA
Trastuzumab With TCH RegimenNA

[back to top]

Number of Patients With at Least One MCS110 Dose Reduction, and Number of Patients With at Least One MCS110 Dose Interruption

patients treated with MCS110 only (NCT02435680)
Timeframe: 4 years

,
InterventionParticipants (Count of Participants)
MCS110 dose reductionMCS110 dose interruption
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine59
MCS110+Carboplatin+Gemcitabine36

[back to top]

Serum C-terminal Telopeptide of Type I Collagen (CTX-I)

"results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days.~Biomarker Analyses performed for MCS110 treated patients only." (NCT02435680)
Timeframe: baseline, day 2, 4, 15, 22, 43, 64, 85, 106, 127, 148

,
Intervention% change from baseline (Mean)
Day 2Day 4Day 15Day 22 (cycle 2 day 1)Day 43 (cycle 3 day 1)Day 64 (cycle 4 day 1)Day 85 (cycle 5 day 1)Day 106 (cycle 6 day 1)Day 127 (cycle 7 day 1)Day 148 (cycle 8 day 1)
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine85.080.269.452.939.329.540.650.268.775.3
MCS110+Carboplatin+Gemcitabine79.472.565.667.964.369.710241.238.740.5

[back to top]

MCS110 Dose Intensity

"Relative dose intensity by categories.~Patients treated with MCS110 only. The dose intensity measures the dose actually taken versus the planned dose, and is expressed in percentage:~<50%: less than 50 % of the planned dose received; 50-<75 %: dose received is 50% or more, but less than 75 %; 75-<90 %: dose received is 75% or more, but less than 90%; 90-<110 %: dose received is 90% or more, but less than 110%" (NCT02435680)
Timeframe: 4 years

,
InterventionParticipants (Count of Participants)
<50%50-<75%75-<90%90-<110%
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine4353
MCS110+Carboplatin+Gemcitabine1873

[back to top]

Tumor Response Per RECIST v1.1 (by Local Investigator Assessment)

CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. (NCT02435680)
Timeframe: 4 years

,
InterventionParticipants (Count of Participants)
PRNon-CR/ Non-progressive diseaseSDprogressive diseaseunknownclinical benefit rateORR
Carboplatin+Gemcitabine6071276
MCS110+Carboplatin+Gemcitabine811942108

[back to top]

Tumor Response Per RECIST v1.1 (by Local Investigator Assessment) Duration of Response

CR: complete response. PR: partial response. SD: stable disease: CBR: clinical benefit rate =CR + PR + SD lasting at least for 6 months. ORR = CR + PR. Efficacy Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. (NCT02435680)
Timeframe: 4 years

Interventionmonths (Median)
MCS110+Carboplatin+Gemcitabine9.6
Carboplatin+Gemcitabine5

[back to top]

Progression Free Survival (PFS) as Per RECIST v1.1 (by Local Investigator Assessment)

PFS Results presented for all MCS110 treated patients (with and without day 8 dose), in line with phase 2 study design. (NCT02435680)
Timeframe: 4 years

Interventionmonths (Median)
All MCS110+Carboplatin+Gemcitabine5.6
Carboplatin+Gemcitabine5.5

[back to top]

Cmax Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)

day 21 (end cycle 1); day 84 (end cycle 4) (NCT02435680)
Timeframe: day 21, day 84

,,
Interventionnanogram /mL (Geometric Mean)
Cmax Carboplatin Day 21Cmax Carboplatin Day 84Cmax Gemcitabine Day 21Cmax Gemcitabine Day 84Cmax dFdU Day 21Cmax dFdU Day 84
Carboplatin+Gemcitabine1120011600237086303770032300
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine1250010000548034003390030300
MCS110+Carboplatin+Gemcitabine124009550275024703910036600

[back to top]

Free MCS110 : Derived Pharmacokinetics (PK) Parameters: AUCtau

AUC tau derived from day 0 to 21 (cycle 1) from day 0 to 21 (cycle 4) Cycle duration is 21 days (NCT02435680)
Timeframe: day 21 (end cycle 1); day 84 (end cycle 4)

,
Interventionday * microgram / mL (Geometric Mean)
day 21day 84
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine29603240
MCS110+Carboplatin+Gemcitabine14301840

[back to top]

Free MCS110 : Derived Pharmacokinetics (PK) Parameters: Cmax

(NCT02435680)
Timeframe: day 21 (end cycle 1); day 84 (end cycle 4)

,
Interventionmicrogram / mL (Geometric Mean)
day 21day 84
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine281319
MCS110+Carboplatin+Gemcitabine186240

[back to top]

AUClast Derived From Plasma Concentration of Carboplatin, Gemcitabine and 2',2'-Difluoro-deoxyuridine (dFdU)

day 21 (end cycle 1); day 84 (end cycle 4) (NCT02435680)
Timeframe: day 21, day 84

,,
Interventionhours * nanogram /mL (Geometric Mean)
AUC Carboplatin Day 21AUC Carboplatin Day 84AUC Gemcitabine Day 21AUC Gemcitabine Day 84AUC dFdU Day 21AUC dFdU Day 84
Carboplatin+Gemcitabine218002050026206320231000211000
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine214001750042702770181000147000
MCS110+Carboplatin+Gemcitabine245001830023902410230000229000

[back to top]

Tumor Associated Macrophage (TAM) and Tumor Infiltrating Lymphocyte (TIL) Content in Pre- and Post-dose Tumor Biopsies.

results expressed as a the ratio change from baseline expressed in percentage: Biopsies were taken at baseline and between Day 29 and Day 43. Patients treated with MCS110 only (NCT02435680)
Timeframe: Baseline, Day 29-43

,
Intervention% change from baseline (Geometric Mean)
CD163CD8
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine43.599.0
MCS110+Carboplatin+Gemcitabine42.1102

[back to top]

Total Colony Stimulation Factor -1 (CSF-I) Circulating Levels

results expressed as a the ratio change from baseline expressed in percentage. Cycle duration is 21 days. These Biomarker Analyses were performed for MCS110 treated patients only. (NCT02435680)
Timeframe: baseline, day 1, 4, 15, 22, 43, 64, 85, 106, 127, 148

,
Intervention% change from baseline (Mean)
Day 1Day 4Day 15Day 22 (cycle 2 day 1)Day 43 (cycle 3 day 1)Day 64 (cycle 4 day 1)Day 85 (cycle 5 day 1)Day 106 (cycle 6 day 1)Day 127 (cycle 7 day 1)Day 148 (cycle 8 day 1)
MCS110 With C1D8 Dose + Carboplatin +Gemcitabine115435019500344007000078000107000103000109000111000
MCS110+Carboplatin+Gemcitabine1104930216003200057900736007930097500110000108000

[back to top]

Circulating Monocytes Cells in Blood

Cycle duration is 21 days results expressed in percentage of cells. Only 1 arm reported as results were available for 1 patient only. (NCT02435680)
Timeframe: day 15, 29, 43, 50

Interventionpercentage (Number)
day 15 CD14+CD16-day 15 CD14+CD16+day 29 (cycle 2 day 8) CD14+CD16-day 29 (cycle 2 day 8) CD14+CD16+day 43 (cycle 3 day 1) CD14+CD16-day 43 (cycle 3 day 1) CD14+CD16+day 50 (cycle 3 day 8) CD14+CD16-day 50 (cycle 3 day 8) CD14+CD16+
MCS110+Carboplatin+Gemcitabine43.554.886.612.29.189.78610

[back to top]

Proportion of Basal Subtype

Proportion of basal subtype was calculated as number of patients who had basal subtype disease divided by all triple-negative breast cancers who were randomized to arms B and C after 6/22/2016 and had intrinsic subtype results. (NCT02445391)
Timeframe: Assessed at registration to step 0 (baseline)

Interventionpercentage of participants (Number)
All Patients Concurrently Randomized to Arms B and C78

[back to top]

3-year Recurrence-Free Survival (RFS) Rate in Basal-Subtype Patients

RFS was defined as time from randomization to local/regional recurrence, distant recurrence or death, whichever occurred first. Cases with incomplete follow up or without adequate disease evaluations were censored at the date last documented to be free of RFS events. 3-year RFS rate was estimated using Kaplan-Meier method. (NCT02445391)
Timeframe: No mandatory timeline, assessed at any time as a standard of care procedure or at the investigator's discretion; data reported every 3 months within 2 years from randomization, every 6 months if 2-3 years.

Interventionpercentage of participants (Number)
Arm B (Cisplatin or Carboplatin) (Enrolled While Arm C Was Open)46.2
Arm C (Capecitabine) (Open to Accrual 6/22/2016)49.3

[back to top] [back to top] [back to top]

3-year Overall Survival (OS) Rate in Basal-Subtype Patients

OS was defined as time from randomization to death from any cause. Patient alive were censored at date of known alive. The 3-year OS rate was estimated using Kaplan-Meier method. (NCT02445391)
Timeframe: Assessed every 3 months within 2 years from randomization, every 6 months if 2-3 years

Interventionpercentage of participants (Number)
Arm B (Cisplatin or Carboplatin) (Enrolled While Arm C Was Open)57.8
Arm C (Capecitabine) (Open to Accrual 6/22/2016)66.2

[back to top]

3-year Invasive Disease-Free Survival (IDFS) Rate in Basal-Subtype Patients

IDFS was defined to be time from randomization to the earliest of documented disease recurrence (local, regional and/or distant), invasive contralateral breast cancer, invasive any other second cancer, or death. Cases with incomplete follow up or without adequate disease evaluations were censored at the date last documented to be free of IDFS events. 3-year IDFS rate was estimated using Kaplan-Meier method. (NCT02445391)
Timeframe: No mandatory timeline, assessed at any time as a standard of care procedure or at the investigator's discretion; data reported every 3 months within 2 years from randomization, every 6 months if 2-3 years.

Interventionpercentage of participants (Number)
Arm B (Cisplatin or Carboplatin) (Enrolled While Arm C Was Open)42.0
Arm C (Capecitabine) (Open to Accrual 6/22/2016)49.4

[back to top] [back to top]

Frequency and Severity of Adverse Effects

Number of treated patients with Adverse Events (grade 3 or higher) observed while receiving randomized therapy, by Preferred term with incidence rate greater than 5%. (NCT02446600)
Timeframe: During treatment period and up to 100 days after stopping the study treatment, up to 39 months.

,,,
InterventionParticipants (Count of Participants)
AnemiaFatigueNeutrophil count decreasedPlatelet count decreasedUrinary tract infectionWhite blood cell decreased
Arm I (Platinum-based Chemotherapy)23351241022
Arm II (Olaparib)281232113
Arm III (Olaparib, Cediranib Maleate)113173152
Japanese Cohort101001

[back to top]

Progression Free Survival Determined Using Response Evaluation Criteria in Solid Tumors Version 1.1 Criteria

Progression free survival (PFS) was defined as the number of months between study enrollment and documentation of disease progression (RECIST 1.1) or death from any cause. Patients still alive and disease free at the last follow-up were censored on the date of last CT Scan, or the CT Scan date prior to two missed assessments. Japanese cohort not included in progression free survival analysis, only included in toxicity assessments. (NCT02446600)
Timeframe: The protocol required lesion assessments every 9 weeks from cycle 1, day 1 for the first year, then every 12 weeks thereafter until disease progression. An average of approximately 10 months.

Interventionmonths (Median)
Arm I (Platinum-based Chemotherapy)10.3
Arm II (Olaparib)8.2
Arm III (Olaparib, Cediranib Maleate)10.4

[back to top]

Overall Survival

Overall survival (OS) was defined as the number of months between study enrollment and death from any cause. Patients still alive at the last follow-up were censored on the date of last contact. Japanese cohort not included in overall survival analysis, the cohort was only included in toxicity assessments. (NCT02446600)
Timeframe: Approximately 30 months

Interventionmonths (Median)
Arm I (Platinum-based Chemotherapy)31.3
Arm II (Olaparib)29.2
Arm III (Olaparib, Cediranib Maleate)30.5

[back to top]

Serum Concentrations of Tremelimumab

Blood samples were collected to determine the serum concentration of tremelimumab. (NCT02453282)
Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3.

Interventionmcg/mL (Mean)
At Week 0: Pre-infusionAt Week 0: End of infusionAt Week 12: Pre-infusionAt Week 12: End of infusionAt follow-up Month 3
Durvalumab + TremelimumabNA22.64.924.80.5

[back to top]

Serum Concentrations of Durvalumab

Blood samples were collected to determine the serum concentration of durvalumab. (NCT02453282)
Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, and at follow-up Month 3.

,
Interventionmicrogram per milliliter (mcg/mL) (Mean)
At Week 0: Pre-infusionAt Week 0: End of infusionAt Week 12: Pre-infusionAt Week 12: End of infusionAt Week 24: Pre-infusionAt Week 24: End of infusionAt follow-up Month 3
Durvalumab + TremelimumabNA444.3140.8506.1197.0553.241.4
Durvalumab MonotherapyNA484.5139.5625.3163.0598.249.3

[back to top]

Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab

Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against durvalumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. (NCT02453282)
Timeframe: At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.

,
InterventionParticipants (Count of Participants)
ADA positive at any timeTreatment-emergent ADA positiveADA positive at baseline and post-baselineADA positive at post-baseline onlyADA positive at baseline onlyTreatment-boosted ADAPersistent positiveTransient positivenAb positive at any visit
Durvalumab + Tremelimumab1481850901
Durvalumab Monotherapy1783860832

[back to top]

Number of Participants With ADA Response to Tremelimumab

Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. Tiered analysis was performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples were employed. Immunogenicity results were analyzed by summarizing the number of participants who developed detectable ADAs against tremelimumab. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. (NCT02453282)
Timeframe: At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.

InterventionParticipants (Count of Participants)
ADA positive at any timeTreatment-emergent ADA positiveADA positive at baseline and post-baselineADA positive at post-baseline onlyADA positive at baseline onlyTreatment-boosted ADAPersistent positiveTransient positivenAb positive at any visit
Durvalumab + Tremelimumab33281284025425

[back to top] [back to top]

Trough Serum Concentration at Steady State (Ctrough_ss) of Durvalumab

Blood samples were collected to determine the Ctrough_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. (NCT02453282)
Timeframe: Pre-dose at Week 12.

Interventionmcg/mL (Mean)
Durvalumab Monotherapy139.5
Durvalumab + Tremelimumab140.8

[back to top]

Time From Randomization to Second Progression (PFS2); PD-L1 (TC >=25%) Analysis Set Population

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy12.7
Durvalumab + Tremelimumab10.9
SoC Chemotherapy10.4

[back to top]

Progression-Free Survival (PFS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs SoC Chemotherapy

The PFS per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) using blinded independent central review (BICR) assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). Progressive disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs) and an absolute increase of at least 5 millimeter (mm), taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab + Tremelimumab3.9
SoC Chemotherapy5.4

[back to top]

PFS2; PD-L1 (TC >=1%) Analysis Set Population

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy10.6
Durvalumab + Tremelimumab9.4
SoC Chemotherapy10.5

[back to top]

PFS2; FAS Population

The PFS2 was defined as the time from the date of randomization to the earliest of the progression events (subsequent to that used for the primary variable PFS and excluding any confirmation of progression scans performed for first progression) or death (ie, date of PFS2 event or censoring - date of randomization + 1). The second progression event was determined by local standard clinical practice which may have included any of the following: objective radiological imaging, symptomatic progression, or death. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to Week 48, then every 8 weeks thereafter until 1st progression. Disease then assessed per local practice until 2nd progression. Assessed up to data cut-off date (maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy9.3
Durvalumab + Tremelimumab9.8
SoC Chemotherapy10.1

[back to top]

PFS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs Durvalumab Monotherapy

The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy4.7
Durvalumab + Tremelimumab3.9
SoC Chemotherapy5.4

[back to top]

PFS; PD-L1 (TC >=1%) Analysis Set Population

The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy3.6
Durvalumab + Tremelimumab2.8
SoC Chemotherapy5.5

[back to top]

PFS; FAS Population

The PFS per RECIST 1.1 using BICR assessments was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdraw from randomized therapy or received another anti-cancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1). The PD was defined as at least a 20% increase in the sum of diameters of TLs and an absolute increase of at least 5 mm, taking as reference the smallest sum of diameters since treatment started including the baseline sum of diameters. Median PFS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy2.8
Durvalumab + Tremelimumab2.9
SoC Chemotherapy5.4

[back to top]

Percentage of Participants APF12; PD-L1 (TC >=1%) Analysis Set Population

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

Interventionpercentage of participants (Number)
Durvalumab Monotherapy27.0
Durvalumab + Tremelimumab20.4
SoC Chemotherapy14.9

[back to top]

Percentage of Participants APF12; FAS Population

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

Interventionpercentage of participants (Number)
Durvalumab Monotherapy22.5
Durvalumab + Tremelimumab19.8
SoC Chemotherapy13.8

[back to top]

Percentage of Participants Alive and Progression Free at 12 Months (APF12); PD-L1 (TC >=25%) Analysis Set Population

The APF12 was defined as the percentage of participants who were alive and progression free per RECIST v1.1 using BICR assessments at 12 months after randomization. The PFS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

Interventionpercentage of participants (Number)
Durvalumab Monotherapy32.3
Durvalumab + Tremelimumab25.8
SoC Chemotherapy14.3

[back to top]

Overall Survival (OS); PD-L1 (TC >=25%) Analysis Set Population, Durvalumab Monotherapy Vs SoC Chemotherapy and Durvalumab + Tremelimumab Vs SoC Chemotherapy

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy16.3
Durvalumab + Tremelimumab11.9
SoC Chemotherapy12.9

[back to top]

OS; PD-L1 (TC >=25%) Analysis Set Population, Durvalumab + Tremelimumab Vs Durvalumab Monotherapy

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy16.3
Durvalumab + Tremelimumab11.9
SoC Chemotherapy12.9

[back to top]

OS; PD-L1 (TC >=1%) Analysis Set Population

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy14.6
Durvalumab + Tremelimumab10.9
SoC Chemotherapy12.3

[back to top]

OS; FAS Population

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02453282)
Timeframe: From baseline until death due to any cause, assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab Monotherapy12.3
Durvalumab + Tremelimumab11.2
SoC Chemotherapy11.8

[back to top]

ORR; PD-L1 (TC >=1%) Analysis Set Population

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionpercentage of participants (Number)
Durvalumab Monotherapy26.5
Durvalumab + Tremelimumab25.3
SoC Chemotherapy33.6

[back to top]

ORR; FAS Population

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of CR or PR. The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionpercentage of participants (Number)
Durvalumab Monotherapy22.2
Durvalumab + Tremelimumab24.7
SoC Chemotherapy30.1

[back to top]

Objective Response Rate (ORR); PD-L1 (TC >=25%) Analysis Set Population

The ORR per RECIST 1.1 using BICR assessments was defined as the percentage of participants with at least 1 visit response of Complete Response (CR) or Partial Response (PR). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionpercentage of participants (Number)
Durvalumab Monotherapy35.6
Durvalumab + Tremelimumab34.4
SoC Chemotherapy37.7

[back to top]

Maximum Serum Concentration at Steady State (Cmax_ss) of Durvalumab

Blood samples were collected to determine the Cmax_ss of durvalumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. (NCT02453282)
Timeframe: Within 1 hour after end of infusion on infusion day at Week 12.

Interventionmcg/mL (Mean)
Durvalumab Monotherapy625.3
Durvalumab + Tremelimumab506.1

[back to top]

Duration of Response (DoR); PD-L1 (TC >=25%) Analysis Set Population

The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab MonotherapyNA
Durvalumab + TremelimumabNA
SoC Chemotherapy4.4

[back to top]

DoR; PD-L1 (TC >=1%) Analysis Set Population

The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab MonotherapyNA
Durvalumab + TremelimumabNA
SoC Chemotherapy4.4

[back to top]

DoR; FAS Population

The DoR per RECIST 1.1 using BICR assessments was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (ie, date of PFS event or censoring - date of first response + 1). The CR was defined as disappearance of all TLs (any pathological lymph nodes selected as TLs must have a reduction in short axis to <10 mm) and PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters as long as criteria for PD are not met). (NCT02453282)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 48 weeks relative to the date of randomization, then every 8 weeks thereafter until confirmed disease progression. Assessed up to the data cut-off date (a maximum of approximately 3 years).

Interventionmonths (Median)
Durvalumab MonotherapyNA
Durvalumab + TremelimumabNA
SoC Chemotherapy4.3

[back to top]

Ctrough_ss of Tremelimumab

Blood samples were collected to determine the Ctrough_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. (NCT02453282)
Timeframe: Pre-dose at Week 12.

Interventionmcg/mL (Mean)
Durvalumab + Tremelimumab4.9

[back to top]

Cmax_ss of Tremelimumab

Blood samples were collected to determine the Cmax_ss of tremelimumab. Steady state was defined as Cycle 4 (Week 12). PK parameters were determined using standard non-compartmental methods. (NCT02453282)
Timeframe: Within 1 hour after end of infusion on infusion day at Week 12.

Interventionmcg/mL (Mean)
Durvalumab + Tremelimumab24.8

[back to top]

Adverse Events as Measured by Number of Events Experienced by All Participants

(NCT02469116)
Timeframe: 30 days after completion of treatment (approximately 22 weeks)

Interventionevents (Number)
Low white blood cell countLow absolute neutrophil countLow platelet countLow hemoglobinAllergy/immunologyCardiovascularCoagulationConstitutional symptomsDermatologyEndocrineGastrointestinalGenitourinary/renalHemorrhageInfection/febrile neutropeniaLymphaticsMetabolic/laboratoryMusculoskeletalNeurologicOcular/visualPainPulmonary
Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF)25214778341426456431292746302272

[back to top]

Efficacy of Regimen as Measured by CA-125 Response

"Progression is defined as one of the following:~Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 ≥ twice the upper limit of normal on two occasions at least one week apart~Patients with elevated CA-125 pretreatment which never normalizes must show evidence of CA-125 ≥ 2 times the nadir value OR > 50% increase from the nadir on two occasions at least one week apart,~Patients with CA-125 in the normal range pretreatment must show evidence of CA-125 ≥ two times the upper limit of normal on two occasions at least one week apart.~Complete response is defined as a CA-125 value <13 confirmed on two occasions at least 2 weeks apart.~Partial Response is defined as a reduction of at least 50% from the original elevated CA-125 value (original value must have been > 50), confirmed on two occasions at least 2 weeks apart.~Stable Disease is defined as not meeting one of the above criteria." (NCT02469116)
Timeframe: Completion of treatment (approximately 18 weeks)

Interventionparticipants (Number)
Complete responsePartial responseStable diseaseProgressive disease
Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF)16101

[back to top]

Incidence of Grade 3-4 Neutropenia as Measured by CTCAE Version 3

(NCT02469116)
Timeframe: Through 30 days after completion of treatment (approximately 22 weeks)

Interventionparticipants (Number)
Grade 3 neutropeniaGrade 4 neutropenia
Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF)40

[back to top]

Progression-Free Survival (PFS) in the Intention-to-treat Population

"PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death (all causes of mortality) if disease progression was not reached. If the participant did not have an event of disease progression according to RECIST criteria (as or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method.~Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.~The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached." (NCT02470585)
Timeframe: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.

Interventionmonths (Median)
Placebo + Carboplatin + Paclitaxel -> Placebo17.3
Veliparib + Carboplatin + Paclitaxel -> Placebo15.2
Veliparib + Carboplatin + Paclitaxel -> Veliparib23.5

[back to top] [back to top]

Progression-Free Survival (PFS) in the BRCA-deficient Population

"PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death prior to the analysis cut-off date, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The analysis of PFS occurred when the protocol-specified number of PFS events was reached.~Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions." (NCT02470585)
Timeframe: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.

Interventionmonths (Median)
Placebo + Carboplatin + Paclitaxel -> Placebo22.0
Veliparib + Carboplatin + Paclitaxel -> Placebo21.1
Veliparib + Carboplatin + Paclitaxel -> Veliparib34.7

[back to top] [back to top] [back to top]

Progression-Free Survival (PFS) in the Homologous Recombination Deficiency Cohort

"PFS was defined as the time from the date that the participant was randomized to the date the participant experienced an event of disease progression, according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1 (as determined by the investigator) or to the date of death if disease progression was not reached. If the participant did not have an event of disease progression or death, the participant's data were censored at the date of their last evaluable disease assessment. PFS was estimated using the Kaplan-Meier method. The primary analysis of PFS occurred when the protocol-specified number of PFS events was reached and was performed in 3 sequentially inclusive populations.~Progressive Disease (PD): At least a 20% increase in the size of target lesions, compared with the smallest size recorded since the treatment started, and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions.~." (NCT02470585)
Timeframe: From randomization until the primary analysis data cut-off date of 03 May 2019, the median duration of follow-up was 28 months.

Interventionmonths (Median)
Placebo + Carboplatin + Paclitaxel -> Placebo20.5
Veliparib + Carboplatin + Paclitaxel -> Placebo18.1
Veliparib + Carboplatin + Paclitaxel -> Veliparib31.9

[back to top]

Time to First Major Adverse Hematologic Event (MAHE) in Part 1

MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible). Time to first occurrence of a MAHE event was defined as the first time to observe an interested event among all the components, starting from the first dose date of study drug administration. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionMonths (Median)
Part 1: Cohort 1 Trilaciclib 200 mg/m^22.6
Part 1: Cohort 2 Trilaciclib 240mg/m^23.0

[back to top]

Occurrence of Grade 3/4 Neutropenia in Part 1

Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^26
Part 1: Cohort 2 Trilaciclib 240mg/m^23

[back to top]

Occurrence of G-CSF Administration in Part 2

Administration of G-CSF was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where G-CSF was administered concurrently was identified bycomparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo24
Part 2: Trilaciclib 240 mg/m^24

[back to top]

Change From Baseline of Platelet Count at the End of Cycle 6, Part 1

Blood samples were collected for local clinical laboratory assessment of platelet count. (NCT02499770)
Timeframe: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6

Interventionx 10^9 cells/L (Mean)
Part 1: Cohort 1 Trilaciclib 200 mg/m^2-72.6
Part 1: Cohort 2 Trilaciclib 240mg/m^2-59.4

[back to top]

Tmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1

Tmax of etoposide and free and total carboplatin in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. (NCT02499770)
Timeframe: Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 Tmax values)

InterventionHours (Median)
Etoposide Day 1 Cycle 1Etoposide Day 3 Cycle 1Free Carboplatin Day 1 Cycle 1Total Carboplatin Day 1 Cycle 1
Part 1: Dose Finding/Expansion1.081.000.520.52

[back to top]

Time of Maximum Observed Concentration (Tmax) of Trilaciclib in Cycle 1, Part 1

Tmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. (NCT02499770)
Timeframe: Days 1 and 3 of Cycle 1 for a 21-day cycle

,
InterventionHours (Median)
Day 1 Cycle 1Day 3 Cycle 1
Part 1: Cohort 1 Trilaciclib 200 mg/m^20.570.52
Part 1: Cohort 2 Trilaciclib 240mg/m^20.500.45

[back to top]

Occurrence of RBC Transfusion in Part 2

Within a cycle, a RBC transfusion event was defined as either 1) an actual RBC transfusion, or 2) eligible for RBC transfusion (defined as hemoglobin <8.0 g/dL). The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions. If a participant did not have any RBC transfusions, they were assigned a value of 0. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

,
InterventionParticipants (Count of Participants)
OverallOn/after Week 5
Part 2: Placebo99
Part 2: Trilaciclib 240 mg/m^262

[back to top]

Number of Participants With Dose Limiting Toxicities by Cohort in Cycle 1, Part 1

"Dose-limiting toxicities (DLTs) were drug-related toxicities defined as follows:~Absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting for ≥ 7 days~≥ Grade 3 neutropenic infection/febrile neutropenia~Grade 4 thrombocytopenia (TCP) or ≥ Grade 3 TCP with bleeding~Unable to start next cycle of chemotherapy due to lack of recovery to an ANC ≥ 1.5 × 10^9/L and platelet count ≥ 100 × 10^9/L~≥ Grade 3 nonhematologic toxicity (nausea, vomiting, and diarrhea failing maximal medical management; fatigue lasting for > 72 hours)~Toxicities not clearly related to etoposide/carboplatin therapy were also considered for the purposes of determining DLTs." (NCT02499770)
Timeframe: Days 1-21 of Cycle 1

,
InterventionParticipants (Count of Participants)
Number of participants meeting ≥1 DLT criteriaGrade 4 TCP or ≥Grade 3 TCP with bleedingUnable to start next cycle of chemotherapy
Part 1: Cohort 1 Trilaciclib 200 mg/m^2211
Part 1: Cohort 2 Trilaciclib 240mg/m^2101

[back to top]

Maximum Observed Plasma Concentration (Cmax) of Trilaciclib in Cycle 1, Part 1

Cmax of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was below the limit of quantification (BLQ) was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted. (NCT02499770)
Timeframe: Days 1 and 3 of Cycle 1 for a 21-day cycle

,
Interventionng/mL (Mean)
Day 1 Cycle 1Day 3 Cycle 1
Part 1: Cohort 1 Trilaciclib 200 mg/m^212401620
Part 1: Cohort 2 Trilaciclib 240mg/m^215702260

[back to top] [back to top]

Cmax of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1

Cmax of etoposide and free and total carboplatin in plasma were determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. For estimation of Cmax, a concentration that was BLQ was assigned a value of zero if it occurred in a profile before the first measurable concentration. If a BLQ value occurred after a measurable concentration in a profile, and was followed by a value above the lower limit of quantification, then the BLQ was treated as missing data. If a BLQ value occurred at the end of the collection interval (after the last quantifiable concentration) it was treated as missing data. If two BLQ values occurred in succession after Cmax, the profile was deemed to have terminated at the first BLQ value and any subsequent concentrations were omitted. (NCT02499770)
Timeframe: Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 Cmax values)

Interventionμg/mL (Mean)
Etoposide Day 1 Cycle 1Etoposide Day 3 Cycle 1Free Carboplatin Day 1 Cycle 1Total Carboplatin Day 1 Cycle 1
Part 1: Dose Finding/Expansion21.920.220.318.8

[back to top]

Best Overall Tumor Response Based on Blinded Independent Central Review (BICR) Assessments in Part 1

Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was determined by BICR. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT02499770)
Timeframe: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)

,
InterventionParticipants (Count of Participants)
CRPRSDPDNot evaluableUnconfirmed CRUnconfirmed PR
Part 1: Cohort 1 Trilaciclib 200 mg/m^21620002
Part 1: Cohort 2 Trilaciclib 240mg/m^20800000

[back to top]

Best Overall Tumor Response Based on BICR Assessments in Part 2

Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was determined by BICR. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT02499770)
Timeframe: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)

,
InterventionParticipants (Count of Participants)
CRPRSDPDNot evaluableUnconfirmed CRUnconfirmed PR
Part 2: Placebo023104005
Part 2: Trilaciclib 240 mg/m^212372104

[back to top]

Best Overall Tumor Response Based on Assessments in Part 2

Tumor response was assessed by CT or MRI. Overall visit response by RECIST v1.1 was derived programmatically using data from TLs, NTLs, & new lesions. Tumor response data were used to determine each participant's time point response & BOR. CR was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. PR was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for PD were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. SD was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT02499770)
Timeframe: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)

,
InterventionParticipants (Count of Participants)
CRPRSDPDNot evaluableUnconfirmed CRUnconfirmed PR
Part 2: Placebo119124106
Part 2: Trilaciclib 240 mg/m^202491004

[back to top]

Best Overall Tumor Response Based on Assessments in Part 1

Tumor response was assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Overall visit response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 was derived programmatically using data from target lesions (TLs), non-target lesions (NTLs), & new lesions. Tumor response data were used to determine each participant's time point response & best overall response (BOR). Complete response (CR) was disappearance of all TLs, any pathological lymph nodes selected as TLs must have reduced in short axis to <10 mm. Partial response (PR) was at least a 30% decrease from baseline in the sum of diameters of TLs, as long as criteria for progressive disease (PD) were not met. PD was a ≥20% increase in the smallest sum of diameters of TLs since treatment started (including baseline) and an absolute increase of ≥5 mm. Stable disease (SD) was neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT02499770)
Timeframe: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% overall survival (OS) events observed (a maximum of 4 years)

,
InterventionParticipants (Count of Participants)
CRPRSDPDNot evaluableUnconfirmed CRUnconfirmed PR
Part 1: Cohort 1 Trilaciclib 200 mg/m^20801010
Part 1: Cohort 2 Trilaciclib 240mg/m^21700000

[back to top]

AUC0-inf of Etoposide and Free and Total Carboplatin in Cycle 1, Part 1

AUC0-inf of etoposide and free and total carboplatin in plasma were determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. (NCT02499770)
Timeframe: Days 1 and 3 of Cycle 1 for a 21-day cycle (carboplatin was only dosed on Day 1 so there are no Day 3 AUC0-inf values)

Interventionh*μg/mL (Mean)
Etoposide Day 1 Cycle 1Etoposide Day 3 Cycle 1Free Carboplatin Day 1 Cycle 1Total Carboplatin Day 1 Cycle 1
Part 1: Dose Finding/Expansion13114650.5137

[back to top]

Area Under the Plasma Concentration Versus Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Trilaciclib in Cycle 1, Part 1

AUC0-inf of trilaciclib in plasma was determined from individual concentration-time data by non-compartmental analysis methods. The actual sampling times in relation to dosing were used. (NCT02499770)
Timeframe: Days 1 and 3 of Cycle 1 for a 21-day cycle

,
Interventionh*ng/mL (Mean)
Day 1 Cycle 1Day 3 Cycle 1
Part 1: Cohort 1 Trilaciclib 200 mg/m^225603110
Part 1: Cohort 2 Trilaciclib 240mg/m^222802960

[back to top]

Nadir of Absolute Neutrophil Count in Cycle 1, Part 2

Cycle nadir was the lowest value for ANC that occurred between start of cycle and end of cycle and was less than the cycle baseline. (NCT02499770)
Timeframe: From baseline to the end of Cycle 1

Interventionx 10^9 cells/L (Mean)
Part 2: Placebo0.815
Part 2: Trilaciclib 240 mg/m^21.899

[back to top]

Time to First MAHE in Part 2

MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelopreservation into a single endpoint. The individual components for MAHE were hospitalization for a hematologic event, febrile neutropenia, death related to treatment, dose delay/reduction due to ANC or platelet counts, prolonged severe neutropenia (duration >5 days), RBC transfusion (actual or eligible) and platelet transfusion (actual or eligible). Time to first occurrence of a MAHE event was defined as the first time to observe an interested event among all the components, starting from the first dose date of study drug administration. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionMonths (Median)
Part 2: Placebo1.0
Part 2: Trilaciclib 240 mg/m^2NA

[back to top]

Progression Free Survival (PFS) Based on Assessments in Part 1

Tumor response was assessed by CT or MRI. PFS was defined as the time (months) from date of first dose date of study drug for participants in Part 1 until date of documented disease progression or death due to any cause, whichever occurred first. More specifically, PFS was determined using all the assessment data up until the last evaluable visit prior to or on the date of i) disease progression as defined by RECIST 1.1 or by clinical criteria as determined by the investigator; or ii) withdrawal of consent; or iii) receiving subsequent anticancer therapy, whichever was earlier. For PFS determined using response data derived programmatically, either clinical progression or progression by RECIST (whichever came first) was considered. Median and inter-quartile range of PFS were calculated using the Kaplan-Meier method. (NCT02499770)
Timeframe: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)

InterventionMonths (Median)
Part 1: Cohort 1 Trilaciclib 200 mg/m^25.3
Part 1: Cohort 2 Trilaciclib 240mg/m^26.3

[back to top]

PFS Based on Assessments in Part 2

Tumor response was assessed by CT or MRI. PFS was defined as the time (months) from date of first dose date of study drug for participants in Part 1 until date of documented disease progression or death due to any cause, whichever occurred first. More specifically, PFS was determined using all the assessment data up until the last evaluable visit prior to or on the date of i) disease progression as defined by RECIST 1.1 or by clinical criteria as determined by the investigator; or ii) withdrawal of consent; or iii) receiving subsequent anticancer therapy, whichever was earlier. For PFS determined using response data derived programmatically, either clinical progression or progression by RECIST (whichever came first) was considered. Median and inter-quartile range of PFS were calculated using the Kaplan-Meier method. (NCT02499770)
Timeframe: Baseline, end of every two 21-day cycles, up until disease progression to a maximum of the time at least 70% OS events observed (a maximum of 4 years)

InterventionMonths (Median)
Part 2: Placebo5.0
Part 2: Trilaciclib 240 mg/m^26.1

[back to top]

OS in Part 2

OS was calculated as the time (months) from date of first dose of study drug for participants in Part 2 to the date of death due to any cause. Participants who did not die during the study were censored at the date last known to be alive. Participants lacking data beyond the day of first dose of study drug had their survival time censored at day of first dose of study drug. OS was not censored if a participant received other anti-tumor treatments after the study drugs. Median and inter-quartile range of OS were calculated using the Kaplan-Meier method. (NCT02499770)
Timeframe: Baseline up until death or a maximum of the time at least 70% OS events observed (a maximum of 4 years)

InterventionMonths (Median)
Part 2: Placebo10.6
Part 2: Trilaciclib 240 mg/m^210.9

[back to top]

OS in Part 1

OS was calculated as the time (months) from date of first dose of study drug for participants in Part 1 to the date of death due to any cause. Participants who did not die during the study were censored at the date last known to be alive. Participants lacking data beyond the day of first dose of study drug had their survival time censored at day of first dose of study drug. OS was not censored if a participant received other anti-tumor treatments after the study drugs. Median and inter-quartile range of OS were calculated using the Kaplan-Meier method. (NCT02499770)
Timeframe: Baseline up until death or a maximum of the time at least 70% OS events observed (a maximum of 4 years)

InterventionMonths (Median)
Part 1: Cohort 1 Trilaciclib 200 mg/m^210.6
Part 1: Cohort 2 Trilaciclib 240mg/m^212.8

[back to top]

Occurrence of Severe (Grade 4) Neutropenia in Part 2

Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo16
Part 2: Trilaciclib 240 mg/m^22

[back to top]

Occurrence of Severe (Grade 4) Neutropenia in Part 1

Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^24
Part 1: Cohort 2 Trilaciclib 240mg/m^20

[back to top]

Change From Baseline of Platelet Count at the End of Cycle 6, Part 2

Blood samples were collected for local clinical laboratory assessment of platelet count. (NCT02499770)
Timeframe: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6

Interventionx 10^9 cells/L (Mean)
Part 2: Placebo-32.7
Part 2: Trilaciclib 240 mg/m^2-54.4

[back to top]

Occurrence of Red Blood Cell (RBC) Transfusion in Part 1

Within a cycle, a RBC transfusion event was defined as either 1) an actual RBC transfusion, or 2) eligible for RBC transfusion (defined as hemoglobin <8.0 g/dL). The occurrence of RBC transfusions was defined as at least 1 cycle with RBC transfusion during the treatment period. For the treatment period, the total number of RBC transfusions was the number of cycles with RBC transfusions. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^24
Part 1: Cohort 2 Trilaciclib 240mg/m^21

[back to top]

Occurrence of Pulmonary Infection SAE in Part 2

"SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A pulmonary infection SAE was a serious event in the MedDRA system organ class infections and infestations and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection." (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo1
Part 2: Trilaciclib 240 mg/m^24

[back to top]

Occurrence of Pulmonary Infection SAE in Part 1

"SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. A pulmonary infection SAE was a serious event in the MedDRA system organ class infections and infestations and a preferred term of bronchitis, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection or viral upper respiratory tract infection." (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^21
Part 1: Cohort 2 Trilaciclib 240mg/m^20

[back to top]

Occurrence of Platelet Transfusion in Part 2

Within a cycle, a platelet transfusion event was defined as either 1) an actual platelet transfusion, or 2) eligible for platelet transfusion (defined as a platelet count ≤10 × 10^9/L). The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo0
Part 2: Trilaciclib 240 mg/m^22

[back to top]

Occurrence of Platelet Transfusion in Part 1

Within a cycle, a platelet transfusion event was defined as either 1) an actual platelet transfusion, or 2) eligible for platelet transfusion (defined as a platelet count ≤10 × 10^9/L). The occurrence of platelet transfusions was defined as at least 1 cycle with platelet transfusion during the treatment period. For the treatment period, the total number of platelet transfusions was the number of cycles with platelet transfusions. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^21
Part 1: Cohort 2 Trilaciclib 240mg/m^20

[back to top]

Occurrence of IV Antibiotic Administration in Part 2

Intravenous antibiotic administration was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where IV antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of IV antibiotic to the start of cycle and end of cycle. The occurrence of IV antibiotic administration was defined as at least 1 cycle with IV antibiotic administration during the treatment period. For the treatment period, the total number of IV antibiotic administrations was the number of cycles with IV antibiotic administrations. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo8
Part 2: Trilaciclib 240 mg/m^28

[back to top]

Occurrence of IV Antibiotic Administration in Part 1

Intravenous antibiotic administration was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where IV antibiotic was administered concurrently was identified by comparing the start and stop dates of each administration of IV antibiotic to the start of cycle and end of cycle. The occurrence of IV antibiotic administration was defined as at least 1 cycle with IV antibiotic administration during the treatment period. For the treatment period, the total number of IV antibiotic administrations was the number of cycles with IV antibiotic administrations. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^24
Part 1: Cohort 2 Trilaciclib 240mg/m^21

[back to top]

Occurrence of Febrile Neutropenia in Part 1

Each febrile neutropenia event (as defined by Common Terminology Criteria for Adverse Events [CTCAE]) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^20
Part 1: Cohort 2 Trilaciclib 240mg/m^20

[back to top]

Duration of Grade 3/4 Neutropenia in Part 1

Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. Within each cycle, duration (days) of Grade 3/4 neutropenia was defined as the number of days from the date of the first ANC value of <1.0 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥1.0 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <1.0 × 10^9/L and 2) no other ANC values <1.0 × 10^9/L occurred between this day and end of cycle. The duration of Grade 3/4 neutropenia only included participants who had at least 1 Grade 3/4 neutropenia event in the cycle, and censoring rules were applied for unresolved Grade 3/4 neutropenia in a cycle. For the treatment period, the overall duration of Grade 3/4 neutropenia was the median value among the durations of Grade 3/4 neutropenia from all cycles. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionDays (Median)
Part 1: Cohort 1 Trilaciclib 200 mg/m^28
Part 1: Cohort 2 Trilaciclib 240mg/m^28

[back to top]

Duration of Grade 3/4 Neutropenia in Part 2

Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. Within each cycle, duration (days) of Grade 3/4 neutropenia was defined as the number of days from the date of the first ANC value of <1.0 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥1.0 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <1.0 × 10^9/L and 2) no other ANC values <1.0 × 10^9/L occurred between this day and end of cycle. The duration of Grade 3/4 neutropenia only included participants who had at least 1 Grade 3/4 neutropenia event in the cycle, and censoring rules were applied for unresolved Grade 3/4 neutropenia in a cycle. For the treatment period, the overall duration of Grade 3/4 neutropenia was the median value among the durations of Grade 3/4 neutropenia from all cycles. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionDays (Median)
Part 2: Placebo8
Part 2: Trilaciclib 240 mg/m^28

[back to top]

Occurrence of Febrile Neutropenia in Part 2

Each febrile neutropenia event (as defined by CTCAE) was captured as an AE. The occurrence of febrile neutropenia was defined as at least 1 febrile neutropenia event during the treatment period. For the treatment period, the total number of febrile neutropenia events was the number of febrile neutropenia events with a unique start date. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo3
Part 2: Trilaciclib 240 mg/m^21

[back to top]

Duration of Severe (Grade 4) Neutropenia in Part 2

Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. Within each cycle, the duration (days) of severe neutropenia was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <0.5 × 10^9/L and 2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. The duration of severe neutropenia only included participants who had at least 1 severe neutropenia event in the cycle, and censoring rules were applied for unresolved severe neutropenia in a cycle. For the treatment period, the overall duration of severe neutropenia was the median value among the durations from all cycles. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionDays (Median)
Part 2: Placebo8
Part 2: Trilaciclib 240 mg/m^23

[back to top]

Occurrence of ESA Administration in Part 2

Administration of ESAs was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo2
Part 2: Trilaciclib 240 mg/m^21

[back to top]

Change From Baseline of Hemoglobin at the End of Cycle 6, Part 1

Blood samples were collected for local clinical laboratory assessment of hemoglobin levels. (NCT02499770)
Timeframe: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6

Interventiong/L (Mean)
Part 1: Cohort 1 Trilaciclib 200 mg/m^2-9.8
Part 1: Cohort 2 Trilaciclib 240mg/m^2-20.1

[back to top]

Change From Baseline of Hemoglobin at the End of Cycle 6, Part 2

Blood samples were collected for local clinical laboratory assessment of hemoglobin levels. (NCT02499770)
Timeframe: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6

Interventiong/L (Mean)
Part 2: Placebo-25.9
Part 2: Trilaciclib 240 mg/m^2-20.6

[back to top]

Occurrence of Infectious SAEs in Part 2

"SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the MedDRA system organ class infections and infestations and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection." (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo2
Part 2: Trilaciclib 240 mg/m^24

[back to top]

Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 1

Blood samples were collected for local clinical laboratory assessment of lymphocyte count. (NCT02499770)
Timeframe: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6

Interventionx 10^9 cells/L (Mean)
Part 1: Cohort 1 Trilaciclib 200 mg/m^20.188
Part 1: Cohort 2 Trilaciclib 240mg/m^20.067

[back to top]

Occurrence of Erythropoietin Stimulating Agent (ESA) Administration in Part 1

Administration of ESAs was collected with concomitant medications, which were coded using WHO-DD Version September 2017. A cycle where an ESA was administered concurrently was identified by comparing the start and stop dates of each administration of an ESA to the start of cycle and end of cycle. The occurrence of ESA administration was at least 1 cycle with an ESA administration during the treatment period. For the treatment period, the total number of ESA administrations was the number of cycles with ESA administrations. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^22
Part 1: Cohort 2 Trilaciclib 240mg/m^20

[back to top]

Nadir of Absolute Neutrophil Count in Cycle 1, Part 1

Cycle nadir was the lowest value for ANC that occurred between start of cycle and end of cycle and was less than the cycle baseline. (NCT02499770)
Timeframe: From baseline to the end of Cycle 1

Interventionx 10^9 cells/L (Mean)
Part 1: Cohort 1 Trilaciclib 200 mg/m^21.198
Part 1: Cohort 2 Trilaciclib 240mg/m^21.653

[back to top]

Occurrence of Dose Reduction in Part 2

Dose reductions were not permitted for trilaciclib, per study protocol. Dose reductions for E/P were derived from changes in the protocol-specified dose on the dosing page and corresponded to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any participant. Simultaneous reductions in the doses of E/P were counted as 1 dose reduction. For the treatment period, the total number of dose reductions was the number of cycles where there was at least 1 dose reduction. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo13
Part 2: Trilaciclib 240 mg/m^23

[back to top]

Occurrence of Dose Reduction in Part 1

Dose reductions were not permitted for trilaciclib, per study protocol. Dose reductions for E/P were derived from changes in the protocol-specified dose on the dosing page and corresponded to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any participant. Simultaneous reductions in the doses of E/P were counted as 1 dose reduction. For the treatment period, the total number of dose reductions was the number of cycles where there was at least 1 dose reduction. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^22
Part 1: Cohort 2 Trilaciclib 240mg/m^23

[back to top]

Duration of Severe (Grade 4) Neutropenia in Cycle 1 of Part 2

In addition to deriving severe (Grade 4) neutropenia using the method described for the primary endpoints, an approach was applied that accounted for participants who did not experience a severe neutropenia event in Cycle 1. For the post-hoc analysis, severe neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. In Cycle 1, the duration (days) of severe neutropenia was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <0.5 × 10^9/L and 2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. The duration of severe neutropenia was set to 0 for participants who did not experience severe neutropenia in Cycle 1. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation. (NCT02499770)
Timeframe: From baseline to the end of Cycle 1

InterventionDays (Median)
Part 2: Placebo0
Part 2: Trilaciclib 240 mg/m^20

[back to top]

Duration of Severe (Grade 4) Neutropenia in Part 1

Severe (Grade 4) neutropenia was defined as at least 1 ANC value <0.5 × 10^9/L during the treatment period. Within each cycle, the duration (days) of severe neutropenia was defined as the number of days from the date of the first ANC value of <0.5 × 10^9/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10^9/L that met the following criteria: 1) occurred after the ANC value of <0.5 × 10^9/L and 2) no other ANC values <0.5 × 10^9/L occurred between this day and end of cycle. The duration of severe neutropenia only included participants who had at least 1 severe neutropenia event in the cycle, and censoring rules were applied for unresolved severe neutropenia in a cycle. For the treatment period, the overall duration of severe neutropenia was the median value among the durations from all cycles. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionDays (Median)
Part 1: Cohort 1 Trilaciclib 200 mg/m^26

[back to top]

Change From Baseline of Lymphocyte Count at the End of Cycle 6, Part 2

Blood samples were collected for local clinical laboratory assessment of lymphocyte count. (NCT02499770)
Timeframe: Baseline, Day 1, Day 3, Day 8, Day 10, and Day 15 of a 21-day cycle x 6

Interventionx 10^9 cells/L (Mean)
Part 2: Placebo-0.203
Part 2: Trilaciclib 240 mg/m^20.104

[back to top]

Occurrence of Infectious SAEs in Part 1

"SAEs were defined as any untoward medical occurrence that at any dose resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity or was a congenital anomaly/birth defect. An infectious SAE was a serious event in the Medical Dictionary for Regulatory Activities (MedDRA) system organ class infections and infestations and a preferred term of anal abscess, bacteraemia, bronchitis, candida infection, chronic sinusitis, conjunctivitis, infection, influenza, nasopharyngitis, oral candidiasis, oral herpes, pharyngitis streptococcal, pneumonia, pneumonia bacterial, respiratory tract infection, sepsis, skin infection, upper respiratory tract infection, urinary tract infection, urosepsis or viral upper respiratory tract infection." (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^22
Part 1: Cohort 2 Trilaciclib 240mg/m^21

[back to top]

Occurrence of Granulocyte-Colony Stimulating Factor (G-CSF) Administration in Part 1

Administration of G-CSF was collected with concomitant medications, which were coded using World Health Organization Drug Dictionary (WHO-DD) Version September 2017. A cycle where G-CSF was administered concurrently was identified by comparing the start and stop dates of each administration of G-CSF to the start of cycle and end of cycle. The occurrence of G-CSF administrations was defined as at least 1 cycle with G-CSF administrations during the treatment period. For the treatment period, the total number of G-CSF administrations was the number of cycles with G-CSF administrations. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 1: Cohort 1 Trilaciclib 200 mg/m^25
Part 1: Cohort 2 Trilaciclib 240mg/m^23

[back to top]

Occurrence of Grade 3/4 Neutropenia in Part 2

Grade 3/4 neutropenia was defined as at least 1 ANC value <1.0 × 10^9/L during the treatment period. (NCT02499770)
Timeframe: From randomization to the end of the treatment period (a minimum of 51 days up to a maximum of 379 days)

InterventionParticipants (Count of Participants)
Part 2: Placebo30
Part 2: Trilaciclib 240 mg/m^214

[back to top]

Disease Control Rate (DCR) at 12 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC

Disease control rate (DCR) at 12 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 48 weeks (-7 days, i.e., 329 days), following the start of study treatment. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy47.3
Monotherapy30.6
Standard of Care48.8

[back to top]

Serum Concentrations of Tremelimumab, Pharmacokinetic Analysis Set

Blood samples were collected to determine the serum concentration of tremelimumab. (NCT02516241)
Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, pre-dose at week 4, and at follow-up Month 3.

Interventionμg/mL (Mean)
Week 0 - PredoseWeek 0 - PostdoseWeek 4 - PredoseWeek 12 - PredoseWeek 12 - PostdoseFollow-up Month 3
Combination TherapyNA24.03.755.4328.10.943

[back to top]

Serum Concentrations of Durvalumab, Pharmacokinetic Analysis Set

Blood samples were collected to determine the serum concentration of durvalumab. (NCT02516241)
Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0, 12 and 24, pre-dose at week 4, and at follow-up Month 3.

,
Interventionμg/mL (Mean)
Week 0 - PredoseWeek 0 - PostdoseWeek 4 - PredoseWeek 12 - PredoseWeek 12 - PostdoseWeek 24 - PredoseWeek 24 - PostdoseFollow-up Month 3
Combination TherapyNA51175.312559415060423.3
MonotherapyNA48478.914457616360019.9

[back to top]

PFS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy

"Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression.~Median PFS was calculated using the Kaplan-Meier technique." (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy2.0
Monotherapy2.0
Standard of Care7.2

[back to top]

Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab, Safety Analysis Set - ADA Evaluable Patients

Serum Samples will be measured for the presence of ADAs and ADA-neutralizing antibodies for Durvalumab using validated assays. Tiered analysis will be performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples will be used. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The category may include patients meeting these criteria who are ADA positive at baseline. (NCT02516241)
Timeframe: At week 0, 4, 12 and 24, and at follow-up Month 3.

,
InterventionParticipants (Count of Participants)
ADA evaluable patientsADA positive at any visit (ADA Prevalence)Treatment-emergent ADA positive (ADA Incidence)Treatment-boosted ADATreatment-induced ADA (Positive Post-baseline only)ADA Positive at Baseline onlyADA Positive Post-baseline and Positive at BaselinePersistently PositiveTransiently PositivenAb Positive at any visit
Combination Therapy29337280288115143
Monotherapy3023111110183852

[back to top]

Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"Fatigue will be based on the question of I have a lack of energy and pain will be based on the question of I have pain, according to GP1 and GP4 in PWB, respectively.~Improvement in fatigue is defined at least 1 point improvement from baseline using GP1 of FACT-BL.~Deterioration in pain is defined as at least 1 point deterioration from baseline using GP4 of FACT-BL." (NCT02516241)
Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

,,
InterventionParticipants (Count of Participants)
Patients with improvement in fatiguePatient with deterioration in pain
Combination Therapy1564
Monotherapy1359
Standard of Care1032

[back to top]

Improvement in Fatigue and Deterioration in Pain Per FACT-BL, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"Fatigue will be based on the question of I have a lack of energy and pain will be based on the question of I have pain, according to GP1 and GP4 in PWB, respectively.~Improvement in fatigue is defined at least 1 point improvement from baseline using GP1 of FACT-BL.~Deterioration in pain is defined as at least 1 point deterioration from baseline using GP4 of FACT-BL." (NCT02516241)
Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

,,
InterventionParticipants (Count of Participants)
Patients with improvement in fatiguePatient with deterioration in pain
Combination Therapy2378
Monotherapy2471
Standard of Care1451

[back to top]

Improvement in Fatigue and Deterioration in Pain Per FACT-BL, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"Fatigue will be based on the question of I have a lack of energy and pain will be based on the question of I have pain, according to GP1 and GP4 in PWB, respectively.~Improvement in fatigue is defined at least 1 point improvement from baseline using GP1 of FACT-BL.~Deterioration in pain is defined as at least 1 point deterioration from baseline using GP4 of FACT-BL." (NCT02516241)
Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

,,
InterventionParticipants (Count of Participants)
Patients with improvement in fatiguePatient with deterioration in pain
Combination Therapy38142
Monotherapy37130
Standard of Care2483

[back to top]

Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"the change from baseline in the following total/index scores will be evaluated as secondary endpoints: FACT-BL TOI (refer to as TOI), FACT-BL Total score, and NFBlSI-18 score.~All the 5 subscales (PWB (0-28), FWB (0-28), EWB (0-24), SWB (0-28), and BlCS(0-48)) are summed as the FACT-BL total score (range 0-156), while the sum of PWB, FWB and BICS constitutes the FACT-BL TOI (range 0-104).~NFBlSI-18 (range 0-72) is based on the scores of 16 items (GP4, C2, BL1, GP3, GE6, GE1, C6, BL5, GF5, GP2, GP1, GP6, C3, GP5, GF3, GF7) and 2 extra items I feel weak all overall and I feel light-headed (dizzy). The range of each item is 0-4.~Higher score represent worse" (NCT02516241)
Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

,,
InterventionScores on a scale (Mean)
NFBLSI - 18 Score (Average overall visits)FACT-BL TOI (Average overall visits)FACT-BL Total score (Average overall visits)
Combination Therapy-3.4-4.9-5.7
Monotherapy-3.8-5.0-6.5
Standard of Care-2.0-3.0-3.2

[back to top]

Alive and Progression-free at 12 Months (APF12), Full Analysis Set

Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy21.4
Monotherapy16.8
Standard of Care15.3

[back to top]

Alive and Progression-free at 12 Months (APF12), PD-L1-High Analysis Set

Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy25.6
Monotherapy21.2
Standard of Care15.0

[back to top]

Alive and Progression-free at 12 Months (APF12), PD-L1-Low/Negative Analysis Set

Alive and progression-free at 12 months (APF12) was defined as the Kaplan-Meier estimate of PFS (per RECIST 1.1 as assessed by investigator) at 12 months. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy15.2
Monotherapy9.7
Standard of Care15.6

[back to top]

Alive at 24 Months (OS24), Full Analysis Set

Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy39.0
Monotherapy31.5
Standard of Care29.0

[back to top]

Alive at 24 Months (OS24), PD-L1-High Analysis Set

Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy43.7
Monotherapy36.0
Standard of Care29.3

[back to top]

Alive at 24 Months (OS24), PD-L1-Low/Negative Analysis Set

Alive at 24 months (OS24) is defined as the Kaplan-Meier estimate of OS at 24 months. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to 24 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy32.1
Monotherapy24.5
Standard of Care28.6

[back to top]

Objective Response Rate (ORR), PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC

Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Interventionpercentage of participants (Number)
Combination Therapy46.8
Monotherapy27.8
Standard of Care48.3

[back to top]

Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"the change from baseline in the following total/index scores will be evaluated as secondary endpoints: FACT-BL TOI (refer to as TOI), FACT-BL Total score, and NFBlSI-18 score.~All the 5 subscales (PWB (0-28), FWB (0-28), EWB (0-24), SWB (0-28), and BlCS(0-48)) are summed as the FACT-BL total score (range 0-156), while the sum of PWB, FWB and BICS constitutes the FACT-BL TOI (range 0-104).~NFBlSI-18 (range 0-72) is based on the scores of 16 items (GP4, C2, BL1, GP3, GE6, GE1, C6, BL5, GF5, GP2, GP1, GP6, C3, GP5, GF3, GF7) and 2 extra items I feel weak all overall and I feel light-headed (dizzy). The range of each item is 0-4.~Higher score represent worse" (NCT02516241)
Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

,,
InterventionScores on a scale (Mean)
NFBLSI - 18 Score (Average overall visits)FACT-BL TOI (Average overall visits)FACT-BL Total score (Average overall visits)
Combination Therapy-3.9-5.8-8.0
Monotherapy-2.0-2.6-2.7
Standard of Care-5.7-8.0-10.1

[back to top]

Change From Baseline in FACT-BL (Derived NFBlSI-18 Score, FACT-BL TOI, and FACT-BL Total Score) by MMRM Analysis, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"the change from baseline in the following total/index scores will be evaluated as secondary endpoints: FACT-BL TOI (refer to as TOI), FACT-BL Total score, and NFBlSI-18 score.~All the 5 subscales (PWB (0-28), FWB (0-28), EWB (0-24), SWB (0-28), and BlCS(0-48)) are summed as the FACT-BL total score (range 0-156), while the sum of PWB, FWB and BICS constitutes the FACT-BL TOI (range 0-104).~NFBlSI-18 (range 0-72) is based on the scores of 16 items (GP4, C2, BL1, GP3, GE6, GE1, C6, BL5, GF5, GP2, GP1, GP6, C3, GP5, GF3, GF7) and 2 extra items I feel weak all overall and I feel light-headed (dizzy). The range of each item is 0-4.~Higher score represent worse outcome." (NCT02516241)
Timeframe: At baseline then every 8 weeks until second progression/death, whichever comes first. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

,,
InterventionScores on a scale (Mean)
NFBLSI - 18 Score (Average overall visits)FACT-BL TOI (Average overall visits)FACT-BL Total score (Average overall visits)
Combination Therapy-3.7-5.5-7.2
Monotherapy-3.1-3.9-4.7
Standard of Care-5.2-7.2-8.8

[back to top]

To Assess the Efficacy of Durvalumab Monotherapy Versus SoC in Terms of OS in PD-L1-High Analysis Set

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Monotherapy14.4
Standard of Care12.1

[back to top]

To Assess the Efficacy of Durvalumab + Tremelimumab Combination Therapy Versus SoC in Terms of OS in Full Analysis Set

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy15.1
Standard of Care12.1

[back to top]

PFS2, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy

"Time from randomization to second progression or death (PFS2) was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy or death (ie, date of PFS2 event or censoring - date of randomization +1).~Median PFS2 was calculated using the Kaplan-Meier technique." (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until first confirmed disease progression, disease then assessed per local practice until 2nd progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy10.7
Monotherapy9.4
Standard of Care11.6

[back to top]

PFS2, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC

"Time from randomization to second progression or death (PFS2) was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy or death (ie, date of PFS2 event or censoring - date of randomization +1).~Median PFS2 was calculated using the Kaplan-Meier technique." (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until first confirmed disease progression, disease then assessed per local practice until 2nd progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy17.2
Monotherapy13.4
Standard of Care11.3

[back to top]

Number of Participants With Anti-Drug Antibody (ADA) Response to Tremelimumab, Safety Analysis Set - ADA Evaluable Patients

Serum Samples will be measured for the presence of ADAs and ADA-neutralizing antibodies for Tremelimumab using validated assays. Tiered analysis will be performed to include screening, confirmatory, and titer assay components, and positive-negative cut points previously statistically determined from drug-naïve validation samples will be used. Persistently positive is defined as having at least 2 post-baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The category may include patients meeting these criteria who are ADA positive at baseline. (NCT02516241)
Timeframe: At week 0, 4, 12 and at follow-up Month 3.

InterventionParticipants (Count of Participants)
ADA evaluable patientsADA positive at any visit (ADA Prevalence)Treatment-emergent ADA positive (ADA Incidence)Treatment-boosted ADATreatment-induced ADA (Positive Post-baseline only)ADA Positive at Baseline onlyADA Positive Post-baseline and Positive at BaselinePersistently PositiveTransiently PositivenAb Positive at any visit
Combination Therapy292645415383312550

[back to top]

PFS2, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"Time from randomization to second progression or death (PFS2) was defined as the time from the date of randomization to the earliest of the progression event subsequent to first subsequent therapy or death (ie, date of PFS2 event or censoring - date of randomization +1).~Median PFS2 was calculated using the Kaplan-Meier technique." (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until first confirmed disease progression, disease then assessed per local practice until 2nd progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy14.6
Monotherapy11.9
Standard of Care11.5

[back to top]

Objective Response Rate (ORR), PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy

Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Interventionpercentage of participants (Number)
Combination Therapy20.4
Monotherapy22.6
Standard of Care50.4

[back to top]

OS, Full Analysis Set - Durvalumab Monotherapy vs SoC

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Monotherapy13.2
Standard of Care12.1

[back to top]

OS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy17.9
Standard of Care12.1

[back to top]

OS, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis were censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02516241)
Timeframe: From randomization date until death due to any cause, assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy11.8
Monotherapy10.9
Standard of Care12.2

[back to top]

PFS, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

"Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression.~Median PFS was calculated using the Kaplan-Meier technique." (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy3.7
Monotherapy2.3
Standard of Care6.7

[back to top]

PFS, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC

"Progression free survival (PFS) (per RECIST 1.1, as assessed by investigator) was defined as the time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the patient withdraws from randomized therapy or receives another anticancer therapy prior to progression.~Median PFS was calculated using the Kaplan-Meier technique." (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy4.1
Monotherapy2.4
Standard of Care5.8

[back to top]

Objective Response Rate (ORR), Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

Interventionpercentage of participants (Number)
Combination Therapy36.3
Monotherapy25.7
Standard of Care49.1

[back to top]

Objective Response Rate (ORR) Based on BICR Assessment According to RECIST 1.1 - Responses Are Confirmed - Durvalumab Cisplatin Ineligible Population

"Objective response rate ORR (per RECIST 1.1 as assessed by investigator) is defined as the number (%) of patients with at least 1 visit response of CR or PR.~unconfirmed responses are excluded." (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (01NOV2017, a maximum of 3 years).

Interventionpercentage of participants (Number)
Monotherapy - PD-L1 High23.0
Monotherapy - PD-L1 Low/Negative17.9
Monotherapy - Total21.0

[back to top]

Duration of Response (DoR), PD-L1-Low/Negative Analysis Set

Duration of response (DoR) (per RECIST 1.1 as assessed by investigator) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy12.9
Monotherapy5.6
Standard of Care5.7

[back to top]

Duration of Response (DoR), PD-L1-High Analysis Set

Duration of response (DoR) (per RECIST 1.1 as assessed by investigator) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy10.0
Monotherapy18.5
Standard of Care5.8

[back to top]

Duration of Response (DoR), Full Analysis Set

Duration of response (DoR) (per RECIST 1.1 as assessed by investigator) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to the data cut-off date (27JAN2020, a maximum of 5 years).

InterventionMonths (Median)
Combination Therapy11.1
Monotherapy9.3
Standard of Care5.7

[back to top]

Disease Control Rate (DCR) at 12 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

Disease control rate (DCR) at 12 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 48 weeks (-7 days, i.e., 329 days), following the start of study treatment. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020)

Interventionpercentage of participants (Number)
Combination Therapy38.0
Monotherapy28.0
Standard of Care50.6

[back to top]

Disease Control Rate (DCR) at 6 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy

Disease control rate (DCR) at 6 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 24 weeks (-7 days, i.e., 161 days), following the start of study treatment. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 6 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy29.2
Monotherapy27.7
Standard of Care59.1

[back to top]

Disease Control Rate (DCR) at 6 Months, PD-L1-High Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Monotherapy vs SoC

Disease control rate (DCR) at 6 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 24 weeks (-7 days, i.e., 161 days), following the start of study treatment. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 6 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy49.8
Monotherapy34.4
Standard of Care53.1

[back to top]

Disease Control Rate (DCR) at 6 Months, Full Analysis Set -Durvalumab + Tremelimumab Combination Therapy vs SoC and Durvalumab Mono Therapy vs SoC

Disease control rate (DCR) at 6 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 24 weeks (-7 days, i.e., 161 days), following the start of study treatment. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 6 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy41.5
Monotherapy31.8
Standard of Care55.5

[back to top]

Disease Control Rate (DCR) at 12 Months, PD-L1-Low/Negative Analysis Set -Durvalumab + Tremelimumab Combination Therapy Versus SoC and Durvalumab + Tremelimumab Combination Therapy Versus Durvalumab Monotherapy

Disease control rate (DCR) at 12 months is defined as the percentage of patients who have a best objective response (BoR) of CR or PR, or who have demonstrated SD for a minimum interval of 48 weeks (-7 days, i.e., 329 days), following the start of study treatment. (NCT02516241)
Timeframe: Tumour scans performed at baseline then every 8 weeks since randomization until confirmed disease progression. Assessed up to 12 months or the data cut-off date (27JAN2020).

Interventionpercentage of participants (Number)
Combination Therapy24.1
Monotherapy24.1
Standard of Care53.3

[back to top]

Pathologic Complete Response Rate (Phase II)

A pathologic complete response (pathCR) rate of at least 35% (>= 40% is desirable) will be of interest. The pathCR rate in each of the treatment step will be estimated, along with the 95% confidence interval. (NCT02530437)
Timeframe: Up to 4 years and 10 months

InterventionParticipants (Count of Participants)
Complete ResponseLess than complete response
Phase 1 B43

[back to top]

Overall Survival

Kaplan-Meier method will be used to estimate the probabilities of overall survival. (NCT02530437)
Timeframe: Up to 4 years and 10 months

Interventionmonths (Median)
Phase 1 B27

[back to top]

Relapse-free Survival

Kaplan-Meier method will be used to estimate the probabilities of relapse-free survival. (NCT02530437)
Timeframe: Up to 4 years and 10 months

Interventionmonths (Median)
Phase 1 B14

[back to top]

Serum Concentrations of Durvalumab

Blood samples were collected to determine the serum concentration of durvalumab. (NCT02542293)
Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0 and 12; pre-dose on Week 24 and at follow-up Month 3

,
Interventionmicrogram per milliliter (µg/mL) (Geometric Mean)
Week 0: Pre-infusionWeek 0: End of infusionWeek 12: Pre-infusionWeek 12: End of infusionWeek 24: Pre-infusionFollow-up Month 3
China: Durvalumab + TremelimumabNA392.772.4448.985.65.4
Global: Durvalumab + TremelimumabNA418.677.5434.3108.88.8

[back to top]

Time From Randomization to Second Progression or Death (PFS2); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets

"The PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary variable PFS, or death (ie, date of PFS2 event or censoring - date of randomization + 1).~bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).

,
Interventionmonths (Median)
bTMB ≥20 mut/Mb analysis setbTMB ≥16 mut/Mb analysis setbTMB ≥12 mut/Mb analysis set
Global: Durvalumab + Tremelimumab10.610.99.9
Global: SoC Chemotherapy8.610.59.0

[back to top]

Number of Participants With Anti-Drug Antibody (ADA) Response to Durvalumab

Blood samples were measured for the presence of ADAs and ADA-neutralizing antibodies (nAb) for durvalumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to >=4 fold during the study period. Persistently positive is defined as having at least 2 post baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive. (NCT02542293)
Timeframe: At Weeks 0, 12, and 24; 3 and 6 months after last dose of study treatment.

,
InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (positive post-baseline only)ADA positive post-baseline and positive at baselinePersistent positiveTransient positivenAb positive at any visitADA positive at baseline and not detected post-baseline
China: Durvalumab + Tremelimumab110101000
Global: Durvalumab + Tremelimumab26120121112313

[back to top]

OS; China Cohort: China Programmed Cell Death Ligand 1 (PD-L1) Negative NSCLC Analysis Set

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02542293)
Timeframe: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the China cohort DCO date (a maximum of approximately 44 months).

Interventionmonths (Median)
China: Durvalumab + Tremelimumab15.0
China: SoC Chemotherapy11.7

[back to top]

Overall Survival (OS); Global Cohort: Blood Tumor Mutational Burden (bTMB) ≥20 Mutations Per Megabase (Mut/Mb) Analysis Set

The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT02542293)
Timeframe: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).

Interventionmonths (Median)
Global: Durvalumab + Tremelimumab11.7
Global: SoC Chemotherapy9.1

[back to top]

Alive and Progression-Free at 12 Months (APF12); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets

"The APF12 was defined as the percentage of participants who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).~bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay." (NCT02542293)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

,
Interventionpercentage of participants (Number)
bTMB ≥20 mut/Mb analysis setbTMB ≥16 mut/Mb analysis setbTMB ≥12 mut/Mb analysis set
Global: Durvalumab + Tremelimumab25.622.021.6
Global: SoC Chemotherapy7.012.313.8

[back to top]

APF12; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets

"The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months).~PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).~Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses." (NCT02542293)
Timeframe: Tumour scans performed at baseline then every 6 weeks up to 12 months.

,,,
Interventionpercentage of participants (Number)
PD-L1-negative NSCLC analysis setFAS
China: Durvalumab + Tremelimumab15.623.9
China: SoC Chemotherapy11.316.6
Global: Durvalumab + Tremelimumab18.220.2
Global: SoC Chemotherapy12.114.9

[back to top]

DoR; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets

"DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of PD (ie, date of PFS event or censoring - date of first response + 1).~PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).~Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.

,,,
Interventionmonths (Median)
PD-L1-negative NSCLC analysis setFAS
China: Durvalumab + Tremelimumab10.512.9
China: SoC Chemotherapy6.16.1
Global: Durvalumab + Tremelimumab10.211.1
Global: SoC Chemotherapy4.94.9

[back to top]

PFS2; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets

"The PFS2 was defined as the time from the date of randomization to the earliest of the progression events subsequent to that used for the primary variable PFS, or death (ie, date of PFS2 event or censoring - date of randomization + 1).~PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).~Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.

,,,
Interventionmonths (Median)
PD-L1-negative NSCLC analysis setFAS
China: Durvalumab + Tremelimumab13.815.5
China: SoC Chemotherapy10.312.9
Global: Durvalumab + Tremelimumab9.19.4
Global: SoC Chemotherapy12.410.4

[back to top]

Duration of Response (DoR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets

"DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response (CR or PR) until the first date of documented progression or death in the absence of PD (ie, date of PFS event or censoring - date of first response + 1).~bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).

,
Interventionmonths (Median)
bTMB ≥20 mut/Mb analysis setbTMB ≥16 mut/Mb analysis setbTMB ≥12 mut/Mb analysis set
Global: Durvalumab + Tremelimumab11.610.611.5
Global: SoC Chemotherapy4.24.34.3

[back to top]

Number of Participants With ADA Response to Tremelimumab

Blood samples were measured for the presence of ADAs and ADA-nAb for tremelimumab using validated assays. ADA prevalence is defined as the percentage of participants with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as the sum of treatment-induced ADA and treatment-boosted ADA. ADA incidence is the percentage of participants who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted to >=4 fold during the study period. Persistently positive is defined as having at least 2 post baseline ADA positive measurements with at least 16 weeks (112 days) between the first and last positive measurements, or an ADA positive result at the last available assessment. Transiently positive is defined as having at least 1 post baseline ADA positive measurement and not fulfilling the conditions for persistently positive. (NCT02542293)
Timeframe: At Weeks 0 and 12; 3 and 6 months after last dose of study treatment.

,
InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (positive post-baseline only)ADA positive post-baseline and positive at baselinePersistent positiveTransient positivenAb positive at any visitADA positive at baseline and not detected post-baseline
China: Durvalumab + Tremelimumab210110200
Global: Durvalumab + Tremelimumab493713642911339

[back to top]

Serum Concentrations of Tremelimumab

Blood samples were collected to determine the serum concentration of tremelimumab. (NCT02542293)
Timeframe: Pre-dose and within 1 hour after end of infusion at Week 0 and 12, and at follow-up Month 3

,
Interventionµg/mL (Geometric Mean)
Week 0: Pre-infusionWeek 0: End of infusionWeek 12: Pre-infusionWeek 12: End of infusionFollow-up Month 3
China: Durvalumab + TremelimumabNA18.43.323.2NA
Global: Durvalumab + TremelimumabNA20.33.420.8NA

[back to top]

Objective Response Rate (ORR); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets

"The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of complete response (CR) or partial response (PR) prior to PD.~bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.~tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).

,
Interventionpercentage of participants (Number)
bTMB ≥20 mut/Mb analysis setbTMB ≥16 mut/Mb analysis setbTMB ≥12 mut/Mb analysis settTMB ≥14 mut/Mb analysis settTMB ≥12 mut/Mb analysis settTMB ≥10 mut/Mb analysis settTMB ≥8 mut/Mb analysis set
Global: Durvalumab + Tremelimumab27.531.228.761.342.637.736.7
Global: SoC Chemotherapy43.346.142.044.741.842.541.2

[back to top]

ORR; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets

"The ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with at least 1 visit response of CR or PR prior to PD.~PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).~Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.~PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.

,,,
Interventionpercentage of participants (Number)
PD-L1-negative NSCLC analysis setFASPD-L1 TC ≥25% analysis setPD-L1 TC ≥50% analysis set
China: Durvalumab + Tremelimumab23.135.954.860.0
China: SoC Chemotherapy41.439.040.646.4
Global: Durvalumab + Tremelimumab23.125.935.237.4
Global: SoC Chemotherapy38.841.743.944.0

[back to top]

OS at Months 12, 18 and 24; Global and China Cohorts: PD-L1-Negative NSCLC and FAS Analysis Sets

"The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1).~PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).~Global Cohort: The FAS included all randomized participants prior to the end of global recruitment.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses." (NCT02542293)
Timeframe: Months 12, 18 and 24

,,,
Interventionpercentage of participants (Number)
Month 12: PD-L1-negative NSCLC analysis setMonth 12: FASMonth 18: PD-L1-negative NSCLC analysis setMonth 18: FASMonth 24: PD-L1-negative NSCLC analysis setMonth 24: FAS
China: Durvalumab + Tremelimumab68.072.844.054.636.044.2
China: SoC Chemotherapy46.453.139.341.817.930.4
Global: Durvalumab + Tremelimumab47.847.734.134.822.125.7
Global: SoC Chemotherapy52.850.034.534.622.323.4

[back to top]

OS at Months 12, 18 and 24; Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, and bTMB ≥12 Mut/Mb Analysis Sets

"The OS was defined as the time from the date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1).~bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay." (NCT02542293)
Timeframe: Months 12, 18 and 24

,
Interventionpercentage of participants (Number)
Month 12: bTMB ≥20 mut/Mb analysis setMonth 12: bTMB ≥16 mut/Mb analysis setMonth 12: bTMB ≥12 mut/Mb analysis setMonth 18: bTMB ≥20 mut/Mb analysis setMonth 18: bTMB ≥16 mut/Mb analysis setMonth 18: bTMB ≥12 mut/Mb analysis setMonth 24: bTMB ≥20 mut/Mb analysis setMonth 24: bTMB ≥16 mut/Mb analysis setMonth 24: bTMB ≥12 mut/Mb analysis set
Global: Durvalumab + Tremelimumab49.350.546.936.235.529.426.124.021.3
Global: SoC Chemotherapy40.848.944.620.428.527.813.618.219.0

[back to top]

OS; Global and China Cohorts: FAS, PD-L1 Tumor Cell (TC) ≥25%, and PD-L1 TC ≥50% Analysis Sets

"The OS was defined as time from date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on last recorded date on which participant was known to be alive.~Global Cohort: The FAS included all randomized participants prior to the end of global recruitment. Any participants recruited in China, after global recruitment had ended, were not included in the FAS.~China Cohort: The China FAS included all randomized participants in the China cohort and were used for all China only efficacy analyses.~PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included the subset of participants in the FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay." (NCT02542293)
Timeframe: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global or China cohort DCO dates, as applicable (a maximum of approximately 44 months) for each cohort.

,,,
Interventionmonths (Median)
FASPD-L1 TC ≥25% analysis setPD-L1 TC ≥50% analysis set
China: Durvalumab + Tremelimumab20.036.636.6
China: SoC Chemotherapy14.115.815.8
Global: Durvalumab + Tremelimumab10.912.214.1
Global: SoC Chemotherapy12.110.410.5

[back to top]

OS; Global Cohort: bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, PD-L1-Negative NSCLC, bTMB <20 Mut/Mb, bTMB Non-Evaluable Population, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets

"OS was defined as time from date of randomization until death due to any cause (ie, date of death or censoring - date of randomization + 1). Any participant not known to have died at time of analysis was censored based on last recorded date on which participant was known to be alive.~bTMB ≥16 mut/Mb, bTMB ≥12 mut/Mb and bTMB <20 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥16 mut/Mb, ≥12 mut/Mb and <20 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.~PD-L1-negative analysis set included the subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by the Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).~bTMB non-evaluable analysis set included the subset of participants in FAS whose bTMB status at baseline could not be determined by the GuardantOMNI CDx assay or whose sample was not available.~tTMB analysis sets are defined same as the bTMB analysis sets (NCT02542293)
Timeframe: From baseline (Day 1, Week 0) until death due to any cause, assessed up to the Global cohort DCO date (a maximum of approximately 44 months).

,
Interventionmonths (Median)
bTMB ≥16 mut/Mb analysis setbTMB ≥12 mut/Mb analysis setPD-L1 negative analysis setbTMB <20 mut/Mb analysis setbTMB non-evaluable analysis settTMB ≥14 mut/Mb analysis settTMB ≥12 mut/Mb analysis settTMB ≥10 mut/Mb analysis settTMB ≥8 mut/Mb analysis set
Global: Durvalumab + Tremelimumab12.110.911.19.99.317.511.111.111.0
Global: SoC Chemotherapy11.910.312.511.510.410.613.910.610.2

[back to top]

PFS; Global and China Cohorts: PD-L1-Negative NSCLC, FAS, PD-L1 TC ≥25%, and PD-L1 TC ≥50% Analysis Sets

"PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective PD or death regardless of whether participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).~PD-L1-negative analysis set included subset of participants in FAS whose PD-L1 status was PD-L1-negative at baseline as defined by Ventana SP263 PD-L1 Assay (ie, <1% PD-L1-membrane expression in tumoral tissue).~Global Cohort: FAS included all randomized participants prior to end of global recruitment.~China Cohort: China FAS included all randomized participants in China cohort and were used for all China only efficacy analyses.~PD-L1 TC ≥25% and PD-L1 TC ≥50% analysis sets included subset of participants in FAS whose PD-L1 status was TC ≥25% and TC ≥50% membrane expression in tumoral tissue, respectively at baseline as defined by the Ventana SP263 PD-L1 Assay." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global or China cohort DCO dates, as applicable (approximately 44 months) for each cohort.

,,,
Interventionmonths (Median)
PD-L1-negative NSCLC analysis setFASPD-L1 TC ≥25% analysis setPD-L1 TC ≥50% analysis set
China: Durvalumab + Tremelimumab5.14.26.86.8
China: SoC Chemotherapy6.06.05.75.7
Global: Durvalumab + Tremelimumab4.14.04.24.6
Global: SoC Chemotherapy5.65.65.45.4

[back to top]

Progression-Free Survival (PFS); Global Cohort: bTMB ≥20 Mut/Mb, bTMB ≥16 Mut/Mb, bTMB ≥12 Mut/Mb, tTMB ≥14 Mut/Mb, tTMB ≥12 Mut/Mb, tTMB ≥10 Mut/Mb, and tTMB ≥8 Mut/Mb Analysis Sets

"The PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as the time from the date of randomization until the date of objective PD or death (by any cause in the absence of progression) regardless of whether the participant withdrew from randomized therapy or received another anticancer therapy prior to progression (ie, date of PFS event or censoring - date of randomization + 1).~bTMB ≥20 mut/Mb, bTMB ≥16 mut/Mb and bTMB ≥12 mut/Mb analysis sets included the subset of participants in FAS whose bTMB status was ≥20 mut/Mb, ≥16 mut/Mb and ≥12 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay.~tTMB ≥14 mut/Mb, tTMB ≥12 mut/Mb, tTMB ≥10 mut/Mb and tTMB ≥8 mut/Mb analysis sets included the subset of participants in FAS whose tTMB status was ≥14 mut/Mb, ≥12 mut/Mb, ≥10 mut/Mb and ≥8 mut/Mb, respectively at baseline as defined by the GuardantOMNI CDx assay." (NCT02542293)
Timeframe: Tumour scans performed at baseline and every 6 weeks up to 48 weeks relative to date of randomization, then every 8 weeks thereafter until confirmed PD/death. Up to Global cohort DCO date (approximately 44 months).

,
Interventionmonths (Median)
bTMB ≥20 mut/Mb analysis setbTMB ≥16 mut/Mb analysis setbTMB ≥12 mut/Mb analysis settTMB ≥14 mut/Mb analysis settTMB ≥12 mut/Mb analysis settTMB ≥10 mut/Mb analysis settTMB ≥8 mut/Mb analysis set
Global: Durvalumab + Tremelimumab4.24.23.98.75.24.34.4
Global: SoC Chemotherapy5.15.55.15.85.85.15.0

[back to top]

Pathologic Complete Response

This is the complete disappearance of invasive cancer in the breast at the time of surgery (NCT02547987)
Timeframe: At the time of definitive surgery (approximately 4-5 months after beginning chemotherapy)

InterventionParticipants (Count of Participants)
Docetaxel/Carboplatin10

[back to top]

Proportion of Subjects Who Experience ≥ Grade 3 Toxicity According Per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 Criteria

Proportion of subjects who experience ≥ Grade 3 toxicity regardless of relation according per Common Toxicity Criteria for Adverse Effects (CTCAE) v4 criteria while receiving pembrolizumab in combination with standard carboplatin/paclitaxel therapy (NCT02549209)
Timeframe: From time of consent to up to a maximum of 7 months(30 days following cessation of treatment )

Interventionproportion of participants (Number)
Investigational Treatment0.74

[back to top]

Objective Response Rates (ORR)

"Objective response rate(ORR) is defined as the percentage of subjects with a partial response or complete response according to immune-related RECIST criteria.~Immune-Related Response Criteria:~Complete Response(irCR): Disappearance of all lesions in two consecutive observations not less than 4 wk apart.~Partial Reponse (irPR): decrease in tumor burden ≥50 %relative to baseline confirmed by a consecutive assessment at least 4 wk after first documentation Stable Disease (irSD): not meeting criteria for irCR or irPR, in absence of irPD" (NCT02549209)
Timeframe: From start of treatment Day 1 (D1) and assessed for a maximum of 18 months

Interventionpercentage of participants (Number)
Investigational Treatment74.4

[back to top]

Duration of Response (DoR) in the All-comers (Full Analysis Set)

Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (NCT02551159)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

InterventionMonths (Median)
Durvalumab + Tremelimumab9.2
Durvalumab11.9
Standard of Care (SOC)4.2

[back to top]

Percentage of Patients Alive at 12, 18 and 24 Months in the All-comers (Full Analysis Set)

Percentage of patients alive (NCT02551159)
Timeframe: 12, 18 and 24 months after randomization

,,
Intervention% of participants (Number)
at 12 monthsat 18 monthsat 24 months
Durvalumab42.831.224.7
Durvalumab + Tremelimumab46.530.722.9
Standard of Care (SOC)43.829.723.2

[back to top]

Overall Survival (OS) Status in the PD-L1 TC/IC High Subgroup - Durvalumab + Tremelimumab Versus Standard of Care (SOC)

Number of participants with Overall Survival (OS) (NCT02551159)
Timeframe: From date of randomization until time of final analysis, an average of approximately 4 years

InterventionParticipants (Count of Participants)
Durvalumab + Tremelimumab162
Durvalumab84
Standard of Care (SOC)77

[back to top]

Percentage of Patients Alive at 12, 18 and 24 Months in the PD-L1 TC/IC High Subgroup

Percentage of patients alive (NCT02551159)
Timeframe: 12, 18 and 24 months after randomization

,,
Intervention% of participants (Number)
at 12 monthsat 18 monthsat 24 months
Durvalumab48.034.727.6
Durvalumab + Tremelimumab49.331.823.9
Standard of Care (SOC)44.030.826.4

[back to top]

Overall Survival (OS) Median Duration in the All-comers (Full Analysis Set)

Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1) (NCT02551159)
Timeframe: From date of randomization until time of final analysis, an average of approximately 4 years

InterventionMonths (Median)
Durvalumab + Tremelimumab10.7
Durvalumab9.9
Standard of Care (SOC)10.3

[back to top]

Progression Free Survival (PFS) in the PD-L1 TC/IC High Subgroup

Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression). Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT02551159)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

InterventionMonths (Median)
Durvalumab + Tremelimumab2.8
Durvalumab2.8
Standard of Care (SOC)5.3

[back to top]

Duration of Response (DoR) in the PD-L1 TC/IC High Subgroup

Time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (NCT02551159)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

InterventionMonths (Median)
Durvalumab + Tremelimumab6.5
Durvalumab12.3
Standard of Care (SOC)4.2

[back to top]

Overall Survival (OS) Median Duration in the PD-L1 TC/IC High Subgroup

Time from the date of randomization until death due to any cause (i.e., date of death or censoring - date of randomization + 1) (NCT02551159)
Timeframe: From date of randomization until time of final analysis, an average of approximately 4 years

InterventionMonths (Median)
Durvalumab + Tremelimumab11.2
Durvalumab10.9
Standard of Care (SOC)10.9

[back to top]

Progression Free Survival (PFS) in the All-comers (Full Analysis Set)

"Time from the date of randomization until the date of objective disease progression or death (by any cause in the absence of progression).~Progression is defined using Response Evaluation Criteria in Solid Tumours criteria (RECIST v1.1), as ≥20% increase in the sum of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions" (NCT02551159)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 24 weeks relative to the date of randomization and then every 8 weeks thereafter, up to approximately 4 years

InterventionMonths (Median)
Durvalumab + Tremelimumab2.8
Durvalumab2.8
Standard of Care (SOC)5.4

[back to top]

Part A: Number of Subjects Reporting Adverse Events (AEs)

Treatment-emergent AEs (TEAEs) defined as events occurring on or after cycle 1, day 1 up to and including 30 days after last dose (approximately 114 days). (NCT02561832)
Timeframe: From day 1 cycle 1, up to and including 30 days after last dose

InterventionParticipants (Number)
Cohort 18
Cohort 27

[back to top]

Incidence of Adverse Events Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (Phases I and II)

Safety will be assessed through summaries of adverse events, vital signs, physical examinations, and clinical laboratory test data. Adverse events will then be quantified via CTCAE 4.0. (NCT02565901)
Timeframe: Up to 3 years

InterventionGrade 3 or 4 AE (Number)
Arm I (Sirolimus, Docetaxel, Carboplatin)2
Arm II (Sirolimus, Docetaxel, Carboplatin)2
Phase 1 Group0

[back to top]

Percentage of Patients With Reduction in Prostate Specific Antigen According to the Prostate Cancer Working Group 2 (PCWG2) Criteria (Phases I and II)

PSA decline from the level at registration will be quantified for each patient and proportion of patients with PSA decline divided by the total number of patients enrolled in study will be described. (NCT02565901)
Timeframe: Baseline to up to 3 years

InterventionPercent with PSA decline (Number)
Arm I (Sirolimus, Docetaxel, Carboplatin)36
Arm II (Sirolimus, Docetaxel, Carboplatin)36
Phase 1 Group50

[back to top]

Change in Tumor Diameter as Measured by Diagnostic Computerized Tomography (CT) Scan

Tumor diameter was measured in centimeters. Mean change in tumor diameter from the baseline measurement at screening is reported. (NCT02567799)
Timeframe: Screening, visits 20 and 3, 6, 11 & 13 months post radiation therapy

,,
InterventionMean Change from Baseline (cm) (Mean)
Visit 203 Months Post-RT6 Months Post-RT9 Months Post-RT11 Months Post-RT13 Months Post-RT
BIO 300 Oral Suspension (1000 mg/Day)0.04-2.29-3.23-3.25-3.10-3.13
BIO 300 Oral Suspension (1500 mg/Day)-1.15-3.54-3.42-5.0-5.9-3.05
BIO 300 Oral Suspension (500 mg/Day)-1.30-2.83-2.43-2.58-2.55-2.33

[back to top]

Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 Administered in the Absence of Chemotherapy

(NCT02567799)
Timeframe: Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose

Interventionng*hr/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)857
BIO 300 Oral Suspension (1000 mg/Day)1493
BIO 300 Oral Suspension (1500 mg/Day)1570

[back to top]

DLCO as Measured by Pulmonary Function Test (PFT)

(NCT02567799)
Timeframe: Screening and months 6 & 13 post radiation therapy completion

,,
InterventionmL/mmHg/Min (Mean)
Baseline6 months post-RT13 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)14.9610.469.48
BIO 300 Oral Suspension (1500 mg/Day)16.1511.2818.95
BIO 300 Oral Suspension (500 mg/Day)12.1210.8311.65

[back to top]

Extent of Esophagitis by Patient Reported Swallowing Diary

The assessment will provide a score (the swallowing questionnaire) from 0 to 5; 1 no problems swallowing; 2 mild soreness only; 3 some difficulty swallowing solids; 4 cannot swallow solids; and 5 cannot swallow liquids. (NCT02567799)
Timeframe: Screening, weeks 1, 2, 3, 4, 5, & 6 and months 3 & 6 post radiation therapy completion

,,
InterventionSwallowing Diary Score (Mean)
Weeks 1-6 Average3 months post-RT6 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)1.541.01.0
BIO 300 Oral Suspension (1500 mg/Day)1.641.61.6
BIO 300 Oral Suspension (500 mg/Day)1.21.01.33

[back to top]

FVC as Measured by Pulmonary Function Test (PFT)

(NCT02567799)
Timeframe: Screening and months 6 & 13 post radiation therapy completion

,,
InterventionLiters (Mean)
Baseline6 months post-RT13 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)2.792.12.19
BIO 300 Oral Suspension (1500 mg/Day)3.512.933.28
BIO 300 Oral Suspension (500 mg/Day)2.462.322.32

[back to top]

Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300

(NCT02567799)
Timeframe: Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6

Interventionng/mL (Mean)
Week 2Week 3Week 4Week 5Week 6
BIO 300 Oral Suspension (1000 mg/Day)5.845.563.826.7124.0

[back to top]

Mean Weekly BIO 300 Trough Levels, Serum Concentration of BIO 300

(NCT02567799)
Timeframe: Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6

,
Interventionng/mL (Mean)
Week 1Week 2Week 3Week 4Week 5Week 6
BIO 300 Oral Suspension (1500 mg/Day)16.029.9614.1222.6623.5424.54
BIO 300 Oral Suspension (500 mg/Day)44.232.65.18.340.712.4

[back to top]

FEV1 as Measured by Pulmonary Function Test (PFT)

(NCT02567799)
Timeframe: Screening and months 6 & 13 post radiation therapy completion

,,
InterventionLiters (Mean)
Baseline6 months post-RT13 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)1.911.291.26
BIO 300 Oral Suspension (1500 mg/Day)2.392.032.39
BIO 300 Oral Suspension (500 mg/Day)1.691.711.61

[back to top]

Mean Area Under the Serum Concentration Curve (AUC) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin

(NCT02567799)
Timeframe: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose

Interventionng*hr/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)1371
BIO 300 Oral Suspension (1000 mg/Day)1578
BIO 300 Oral Suspension (1500 mg/Day)1821

[back to top]

Mean Area Under the Serum Concentration Curve (AUC) of Carboplatin When Administered in Combination With BIO 300

(NCT02567799)
Timeframe: Week1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose

Interventionng*hr/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)30810.04
BIO 300 Oral Suspension (1000 mg/Day)41785.18
BIO 300 Oral Suspension (1500 mg/Day)41753.3

[back to top]

Mean Area Under the Serum Concentration Curve (AUC) of Paclitaxel When Administered in Combination With BIO 300

(NCT02567799)
Timeframe: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose

Interventionng*hr/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)1236.51
BIO 300 Oral Suspension (1000 mg/Day)1796.1
BIO 300 Oral Suspension (1500 mg/Day)755.27

[back to top]

Quality of Life (QOL) as Measured by University of California, San Diego-Shortness of Breath Questionnaire (UCSD-SOBQ) Patient Reported Outcome Questionnaire.

"The UCSD-SOBQ is a 24-item patient self-reported questionnaire where items are scored on a 6-point scale (0, not at all to 5, maximal or unable to-do because of breathlessness). Total scores range from 0 to 120 and lower scores indicate better quality of life." (NCT02567799)
Timeframe: Screening and months 3, 6, & 13 post radiation therapy completion

,,
InterventionUCSD-SOBQ Total Score (Mean)
Screening3 months post-RT6 months post-RT13 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)29.938.054.739.8
BIO 300 Oral Suspension (1500 mg/Day)13.923.024.823.2
BIO 300 Oral Suspension (500 mg/Day)19.437.046.864.0

[back to top]

Percent Change From Baseline in Expression Levels of Serum TGF-beta Isoform 1 (TGFB1)

Measuring change from baseline (screening visit) of TGF-beta isoform 1 (TGFB1) (NCT02567799)
Timeframe: Screening, once weekly during weeks 1-6 of concurrent chemoradiotherapy prior to BIO 300, paclitaxel, and carboplatin dose, and once at the end of consolidation, 3 months and 6 months after the completion of RT

,,
InterventionPercent change from baseline (Mean)
Week 1Week 2Week 3Week 4Week 5Week 6After consolidation therapy3 months post-RT6 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)96.7127.560.169.061.769.374.3144.9130.5
BIO 300 Oral Suspension (1500 mg/Day)117.396.774.455.851.233.460.883.161.2
BIO 300 Oral Suspension (500 mg/Day)141.8130.3108.690.688.5142.868.7205.7106.5

[back to top]

Quality of Life (QOL) as Measured by Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) Patient Reported Outcome Questionnaire.

The Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) questionnaire is a 36-item self-reporting instrument that measures quality of life specific to patients with cancer. Items are rated on a 5 item (point) Likert Scale, from 0 (not at all) to 4 (very much). Total scores range from 0 to 136 and higher scores indicate better quality of life. The FACT-TOI questionnaire was scored according to FACT-L Scoring Guidelines Version 4. (NCT02567799)
Timeframe: Screening and months 3, 6, & 13 post radiation therapy completion

,,
InterventionFACT-TOI Total Score (Mean)
Screening3 months post-RT6 months post-RT13 months post-RT
BIO 300 Oral Suspension (1000 mg/Day)46.453.042.352.0
BIO 300 Oral Suspension (1500 mg/Day)47.147.644.447.0
BIO 300 Oral Suspension (500 mg/Day)66.654.555.450.8

[back to top]

Mean Maximum Serum Concentration (Cmax) of BIO 300 Administered in the Absence of Chemotherapy

(NCT02567799)
Timeframe: Day 1, prior to 1st dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post dose

Interventionng/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)174
BIO 300 Oral Suspension (1000 mg/Day)302
BIO 300 Oral Suspension (1500 mg/Day)388

[back to top]

Weekly Paclitaxel Trough Levels, Plasma Concentration of Paclitaxel and Carboplatin

Serum trough levels of paclitaxel and carboplatin were measured. Carboplatin trough levels were below the limit of quantification at all timepoints and are therefore reported as zero ng/mL. (NCT02567799)
Timeframe: Concurrent chemoradiotherapy weeks 1, 2, 3, 4, 5 and 6

,
Interventionng/mL (Mean)
Week 1Week 2Week 3Week 4Week 5Week 6
Carboplatin000000
Paclitaxel1.041.091.531.831.901.92

[back to top]

Mean Maximum Serum Concentration (Cmax) of BIO 300 When Administered in Combination With Paclitaxel and Carboplatin

(NCT02567799)
Timeframe: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to 1st dose then 0.5, 1, 2, 3, 4, 8, and 24 hours post dose

Interventionng/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)155
BIO 300 Oral Suspension (1000 mg/Day)427
BIO 300 Oral Suspension (1500 mg/Day)414

[back to top]

Mean Maximum Serum Concentration (Cmax) of Carboplatin When Administered in Combination With BIO 300

(NCT02567799)
Timeframe: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose

Interventionng/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)7594
BIO 300 Oral Suspension (1000 mg/Day)9938.33
BIO 300 Oral Suspension (1500 mg/Day)12883.33

[back to top]

Mean Maximum Serum Concentration (Cmax) of Paclitaxel When Administered in Combination With BIO 300

(NCT02567799)
Timeframe: Week 1 or 2, during the 1st or 2nd chemotherapy infusion, prior to BIO 300 dose then 0.5, 1, 2, 3, 4, 8 and 24 hours post initial dose

Interventionng/mL (Mean)
BIO 300 Oral Suspension (500 mg/Day)665.5
BIO 300 Oral Suspension (1000 mg/Day)1026.5
BIO 300 Oral Suspension (1500 mg/Day)307.6

[back to top]

Number of Participants With Adverse Events Throughout the Study

(NCT02567799)
Timeframe: Day 1 up to month 13 post radiation or 12 months post chemotherapy consolidation for surgical participants.

InterventionParticipants (Number)
BIO 300 Oral Suspension (500 mg/Day)7
BIO 300 Oral Suspension (1000 mg/Day)7
BIO 300 Oral Suspension (1500 mg/Day)7

[back to top]

Number of Participants With Pulmonary Fibrosis Assessed by Four-dimensional Computerized Tomography (4D-CT)

(NCT02567799)
Timeframe: Screening, visits 20 & 37 and 9 & 13 months post radiation therapy for non-surgical participants; screening only for surgical participants

InterventionParticipants (Count of Participants)
BIO 300 Oral Suspension (500 mg/Day)0
BIO 300 Oral Suspension (1000 mg/Day)0
BIO 300 Oral Suspension (1500 mg/Day)0

[back to top]

Progression-Free Survival (PFS), Groups A-D Only

Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. (NCT02574078)
Timeframe: up to approximately 48 months

InterventionMonths (Median)
Group A, Cohort A, Nivo15.0
Group A, Cohort A, Beva + Nivo6.7
Group A, Cohort A, Beva6.0
Group A, Cohort B, Nivo5.9
Group A, Cohort B, Peme + Nivo8.1
Group A, Cohort B, Peme5.0
Group B, Nivo9.6
Group B, BSC2.3
Group C, Nivo2.7
Group C, ICC6.7
Group D, Nivo + Erlo11.0
Group D, Erlo11.0

[back to top]

Progression-Free Survival (PFS), Group E Only

Progression-free survival (PFS) is defined as the time from randomization to the date of the first documented tumor progression, as determined by investigators (per RECIST v1.1), or death due to any cause, whichever occurs first. (NCT02574078)
Timeframe: up to approximately 48 months

Interventionmonths (Median)
Group E9.63

[back to top]

Overall Survival (OS), Groups A-C Only

Overall survival (OS) is defined as the time from randomization to the date of death. (NCT02574078)
Timeframe: up to approximately 60 months

InterventionMonths (Median)
Group A, Cohort A, Nivo20.0
Group A, Cohort A, Beva + Nivo30.8
Group A, Cohort A, Beva18.1
Group A, Cohort B, Nivo28.9
Group A, Cohort B, Peme + Nivo17.4
Group A, Cohort B, Peme18.4
Group B, NivoNA
Group B, BSC13.6
Group C, Nivo3.9
Group C, ICC15.8

[back to top]

Objective Response Rate (ORR), Groups A-E

"Objective response rate (ORR) is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR). Best overall response (BOR) is defined as the best response designation, recorded between the date of first dose and the date of the initial objectively documented tumor progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.~Confidence interval based on the Clopper and Pearson method." (NCT02574078)
Timeframe: up to approximately 48 months

InterventionPercentage of participants (Number)
Group A, Cohort A, Nivo23.1
Group A, Cohort A, Beva + Nivo16.7
Group A, Cohort A, Beva12.5
Group A, Cohort B, Nivo29.4
Group A, Cohort B, Peme + Nivo21.2
Group A, Cohort B, Peme3.1
Group B, Nivo18.8
Group B, BSC5.9
Group C, Nivo20.8
Group C, ICC15.4
Group D, Nivo + Erlo64.7
Group D, Erlo62.5
Group E23.1

[back to top]

Duration of Response (DOR), Groups A-D Only

"Duration of response (DOR) is defined as the time from first confirmed response (complete response (CR) or partial response (PR)) to the date of the initial objectively documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first.~Median computed using Kaplan-Meier method." (NCT02574078)
Timeframe: up to approximately 48 months

Interventionmonths (Median)
Group A, Cohort A, Nivo12.780
Group A, Cohort A, Beva + NivoNA
Group A, Cohort A, Beva17.084
Group A, Cohort B, Nivo12.912
Group A, Cohort B, Peme + Nivo8.542
Group A, Cohort B, Peme14.982
Group B, NivoNA
Group B, BSCNA
Group C, Nivo3.877
Group C, ICC2.940
Group D, Nivo + Erlo8.805
Group D, Erlo10.152

[back to top] [back to top]

Overall Survival (OS), Group D Only

Overall survival (OS) is defined as the time from randomization to the date of death. (NCT02574078)
Timeframe: up to approximately 60 months

Interventionmonths (Median)
Group D, Nivo + ErloNA
Group D, Erlo34.8

[back to top]

Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Respiration Rate Increase/Decrease

The number of participants with maximal on-treatment (TR) changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) maximal Respiration Rate (RR) were reported by using criteria: Ic./Dc. BS RR <20 breaths per minute (breaths/min), on TR change =<5 breaths/min, >5 - =<10 breaths/min, >10 breaths/min and missing. Ic./Dc. BS RR missing, on TR change missing. Ic./Dc. BS RR >=20 breaths/min, on TR change =<5 breaths/min, >5 - =<10 breaths/min, >10 breaths/min and missing. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to 71.5 months)

,,
InterventionParticipants (Count of Participants)
Ic. BS RR <20 breaths/min, on TR change =<5 breaths/minIc.BS RR<20 breaths/min, on TR change >5 - = <10 breaths/minIc. BS RR <20 breaths/min, on TR change >10 breaths/minIc. BS RR <20 breaths/min, on TR change missingIc. BS RR >=20 breaths/min, on TR change =<5 breaths/minIc.BS RR >=20 breaths/min, on TR change >5 - =<10 breaths/minIc. BS RR >=20 breaths/min, on TR change >10 breaths/minIc. BS RR >=20 breaths/min, on TR change missingIc. BS RR missing, on TR change missingDc. BS RR <20 breaths/min, on TR change =<5 breaths/minDc. BS RR <20 breaths/min, on TR change >5 - =<10 breaths/minDc. BS RR <20 breaths/min, on TR change >10 breaths/minDc. BS RR <20 breaths/min, on TR change missingDc. BS RR >=20 breaths/min, on TR ch =<5 breaths/minDc.BS RR >=20 breaths/min, on TR change >5 - =<10 breaths/minDc. BS RR >=20 breaths/min, on TR change >10 breaths/minDc. BS RR >=20 breaths/min, on TR change missingDc. BS RR missing, on TR change missing
Avelumab Biweekly2211811189537623280117914476
Avelumab Weekly22413146841212362045813221
Chemotherapy3062621412420151132581141012231511

[back to top]

Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)

OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Biweekly20.1
Chemotherapy14.9

[back to top]

Overall Survival (OS) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)

OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Weekly19.3
Chemotherapy15.3

[back to top]

Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High PD-L1+ Full Analysis Set

Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionpercentage of participants (Number)
Avelumab Biweekly37.7
Chemotherapy30.1

[back to top]

Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High PD-L1+ Modified Full Analysis Set

Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionpercentage of participants (Median)
Avelumab Weekly34.6
Chemotherapy30.2

[back to top]

Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in Moderate and High PD-L1+ Full Analysis Set

Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionpercentage of participants (Number)
Avelumab Biweekly33.5
Chemotherapy30.3

[back to top]

Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)

OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Biweekly18.7
Chemotherapy13.3

[back to top]

Overall Survival (OS) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)

OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Weekly16.8
Chemotherapy13.0

[back to top]

Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Systolic Blood Pressure Increase/Decrease and Maximal Diastolic Blood Pressure Increase/Decrease

The number of participants with maximal on-treatment changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) Systolic Blood Pressure (SBP) and diastolic blood pressure (DBP) (millimeter of mercury [mmHg]) were reported by using criteria: Ic./Dc. BS SBP <140 mmHg and >=140 mmHg, on maximal treatment (TR) change =<20 mmHg, >20 - =<40 mmHg, >40 mmHg and missing; Ic./Dc. BS SBP missing, on maximal treatment (TR) change missing; Ic./Dc. BS DBP <90 mmHg and >= 90 mmHg, on maximal TR change =<20 mmHg, >20 - =<40 mmHg, >40 mmHg and missing; Ic./Dc. BS DBP missing on maximal TR change missing. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
Ic. BS SBP <140 mmHg, on TR change =<20 mmHgIc. BS SBP <140 mmHg, on TR change >20 - =<40 mmHgIc. BS SBP <140 mmHg, on TR change >40 mmHgIc. BS SBP <140 mmHg, on TR change missingIc. BS SBP >=140 mmHg, on TR change =<20 mmHgIc. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHgIc. BS SBP >=140 mmHg, on TR change >40 mmHgIc. BS SBP > = 140 mmHg, on TR change missingIc. BS SBP missing, on TR change missingDc. BS SBP <140 mmHg, on TR change =<20 mmHgDc. BS SBP <140 mmHg, on TR change >20 - =<40 mmHgDc. BS SBP <140 mmHg, on TR change >40 mmHgDc. BS SBP <140 mmHg, on TR change missingDc. BS SBP >=140 mmHg, on TR change =<20 mmHgDc. BS SBP >=140 mmHg, on TR change >20 - =<40 mmHgDc. BS SBP >=140 mmHg, on TR change >40 mmHgDc. BS SBP > = 140 mmHg, on TR change missingDc. BS SBP missing, on TR change missingIc. BS DBP <90 mmHg, on TR change =<20 mmHgIc. BS DBP <90 mmHg, on TR change >20 - =<40 mmHgIc. BS DBP <90 mmHg, on TR change >40 mmHgIc. BS DBP <90 mmHg, on TR change missingIc. BS DBP missing, on TR change missingIc. BS DBP >=90 mmHg, on TR change =<20 mmHgIc. BS DBP >=90 mmHg, on TR change >20 - =<40 mmHgIc. BS DBP >=90 mmHg, on TR change >40 mmHgIc. BS DBP >=90 mmHg, on TR change missingDc. BS DBP <90 mmHg, on TR change =<20 mmHgDc. BS DBP <90 mmHg, on TR change >20 - =<40 mmHgDc. BS DBP <90 mmHg, on TR change >40 mmHgDc. BS DBP <90 mmHg, on TR change missingDc. BS DBP >=90 mmHg, on TR change =<20 mmHgDc. BS DBP >=90 mmHg,on TR change >20 - =<40 mmHgDc. BS DBP >=90 mmHg, on TR change >40 mmHgDc. BS DBP >=90 mmHg, on TR change missingDc. BS DBP missing, on TR change missing
Avelumab Biweekly219611614417030220706141125123027248017024000279383171112100
Avelumab Weekly20956164265020204707461510202603715012111264331559010
Chemotherapy2781041021785121322691213234182140245123128000415321231810001

[back to top]

Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Weight Increase/Decrease

The number of participants with maximal on-treatment changes from baseline in Increase (Ic.)/Decrease (Dc.) in maximal weight were reported by using criteria: Ic./Dc. From baseline, on treatment (TR) change <10 percentage (%), >=10% and missing. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
Ic. from baseline, on TR change <10%Ic. from baseline, on TR change >=10%Ic. from baseline, on TR change missingDc. from baseline, on TR change <10%Dc. from baseline, on TR change >=10%Dc. from baseline, on TR change missing
Avelumab Biweekly30238212964421
Avelumab Weekly28028102585010
Chemotherapy43639254235225

[back to top]

Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Electrocardiogram (ECG) Parameters

ECG parameters included heart rate, PR interval, QRS interval, corrected QT interval using Bazett's formula (QTcB) and corrected QT interval using Fridericia's formula (QTcF). PCSA criteria for abnormal value of ECG parameters: any heart rate <= 50 bpm and decrease from baseline >=20 bpm , any hear rate >= 120 bpm and increase from baseline >= 20 bpm; PR interval: >= 220 milliseconds (ms) and increase from baseline >= 20 ms; QRS interval >= 120 ms; QTcF > 450 ms, > 480 ms, > 500 ms, QTcF increase from baseline > 30 ms and QTcF increase from baseline > 60 ms; QTcB > 450 ms, > 480 ms, > 500 ms, QTcB increase from baseline > 30 ms and QTcB increase from baseline > 60 ms. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
Heart Rate <= 50 bpm and decrease from baseline >= 20 bpmHeart Rate >= 120 bpm and decrease from baseline >= 20 bpmPR interval >= 220 ms and increase from baseline >= 20 msQRS interval >= 120 msQTcF > 450 msQTcF > 480 msQTcF > 500 msQTcF increase from baseline > 30 msQTcF increase from baseline > 60 msQTcB > 450 msQTcB > 480 msQTcB > 500 msQTcB increase from baseline > 30 msQTcB increase from baseline > 60 ms
Avelumab Biweekly1100181953206491363211
Avelumab Weekly16510134112131115257
Chemotherapy073152411539137024164919

[back to top]

Number of Participants With Shift From Baseline to Greater Than or Equal to (>=) Grade 3 in Laboratory Parameter Values Based on National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 4.03

Number of participants with shifts from Baseline values (Grade 0/1/2/3) to abnormal post-baseline values (shift to >= Grade 4) were reported as per NCI-CTCAE, v4.03 graded from Grade 1 to 5. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Death. Shifts in laboratory parameter (anemia, lymphocyte count decreased, neutrophil count decreased, platelet count decreased, white blood cell count decreased, alanine aminotransferase increased, alkaline phosphatase increased, aspartate aminotransferase increased, blood bilirubin increased, creatine phosphokinase increased, creatinine increased and Hyperglycemia) were reported. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
Anemia: Grade 0 to Grade 3Anemia: Grade 1 to Grade 3Anemia: Grade 2 to Grade 3Lymphocyte count decreased: Grade 0 to Grade 3Lymphocyte count decreased: Grade 0 to Grade 4Lymphocyte count decreased: Grade 1 to Grade 3Lymphocyte count decreased: Grade 2 to Grade 3Lymphocyte count decreased: Grade 2 to Grade 4Lymphocyte count decreased: Grade 3 to Grade 4Neutrophil count decreased: Grade 0 to Grade 3Neutrophil count decreased: Grade 0 to Grade 4Neutrophil count decreased: Grade 1 to Grade 3Platelet count decreased: Grade 0 to Grade 3Platelet count decreased: Grade 0 to Grade 4Platelet count decreased: Grade 1 to Grade 3White blood cell count decreased: Grade 0 to Grade 3White blood cell count decreased: Grade 0 to Grade 4Alanine aminotransferase increased: Grade 0 to Grade 3Alanine aminotransferase increased: Grade 0 to Grade 4Alanine aminotransferase increased: Grade 1 to Grade 3Alkaline phosphatase increased: Grade 0 to Grade 3Alkaline phosphatase increased: Grade 1 to Grade 3Alkaline phosphatase increased: Grade 1 to Grade 4Alkaline phosphatase increased: Grade 2 to Grade 3Aspartate aminotransferase increased: Grade 0 to Grade 3Aspartate aminotransferase increased: Grade 0 to Grade 4Aspartate aminotransferase increased: Grade 1 to Grade 3Blood bilirubin increased: Grade 0 to Grade 3Blood bilirubin increased: Grade 0 to Grade 4Creatine phosphokinase increased: Grade 0 to Grade 3Creatine phosphokinase increased: Grade 0 to Grade 4Creatine phosphokinase increased: Grade 1 to Grade 4Creatine phosphokinase increased: Grade 2 to Grade 3Creatinine increased: Grade 0 to Grade 3Creatinine increased: Grade 1 to Grade 3Hyperglycemia: Grade 0 to Grade 3Hyperglycemia: Grade 0 to Grade 4
Avelumab Biweekly4441612700401000001211010071000650060210
Avelumab Weekly2561521060043013131810330142041501140200
Chemotherapy5830631312121165251182002411532111032130100041353

[back to top]

Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in Moderate and High PD-L1+ Modified Full Analysis Set

Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionpercentage of participants (Number)
Avelumab Weekly30.6
Chemotherapy30.6

[back to top]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and AEs of Special Interest (AESIs)

Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged in participant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. The term TEAEs were those events with onset dates occurring during the on-treatment period or if the worsening of an event is during the on-treatment period TEAEs included both serious TEAEs and non-serious TEAEs. Any AE that was suspicious to be a potential Immune-related adverse event (irAE) including infusion related reactions were considered AESIs. Number of participants with TEAEs and AESIs were reported. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
TEAEsAESIs
Avelumab Biweekly346158
Avelumab Weekly308160
Chemotherapy484173

[back to top]

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ HRQoL Analysis Set

EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL. (NCT02576574)
Timeframe: Baseline, End of treatment (up to Week 283.9)

Interventionscore on a scale (Mean)
Avelumab Biweekly-0.3
Chemotherapy-6.1

[back to top]

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life (EORTC QLQ-C30) Global Health Status at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set

EORTC QLQ-C30 was a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consisted of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). The EORTC QLQ-C30 GHS/QoL score ranged from 0 to 100; High score indicated better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL. (NCT02576574)
Timeframe: Baseline, End of treatment (Week 283.9)

Interventionscore on a scale (Mean)
Avelumab Weekly-12.9
Chemotherapy-4.5

[back to top] [back to top]

Change From Baseline in European Quality Of Life 5-dimensions (EQ-5D-5L) Visual Analog Scale (VAS) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set

EQ-5D-5L is comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses are used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 is the worst health you can imagine and 100 is the best health you can imagine. (NCT02576574)
Timeframe: Baseline, End of treatment (Week 283.9)

Interventionmillimeter (Mean)
Avelumab Weekly-10.3
Chemotherapy-3.9

[back to top]

Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)

DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Biweekly35.9
Chemotherapy8.4

[back to top]

Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)

DOR was defined for participants with confirmed response, as the time from first documentation of objective response (Complete Response [CR] or Partial Response [PR]) to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Weekly19.4
Chemotherapy8.4

[back to top]

Overall Survival (OS) in Full Analysis Set (FAS)

OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Biweekly15.0
Chemotherapy14.3

[back to top]

Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1) + Full Analysis Set (FAS)

PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Biweekly8.4
Chemotherapy5.6

[back to top]

Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in High Programmed Death Ligand 1 (PD-L1) + Modified Full Analysis Set (mFAS)

PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Weekly7.5
Chemotherapy5.6

[back to top]

Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Full Analysis Set (FAS)

PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Biweekly6.9
Chemotherapy5.6

[back to top]

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ Modified HRQoL Analysis Set

EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items). (NCT02576574)
Timeframe: Baseline, End of treatment (up to Week 283.9)

,
Interventionscore on a scale (Mean)
DyspneaCoughingHemoptysisSore mouthDysphagiaPeripheral neuropathyAlopeciaPain in chestPain in arm or shoulderPain in other parts
Avelumab Weekly6.1-0.6-0.60.63.80.6-2.52.54.410.1
Chemotherapy4.9-5.20.01.9-0.59.915.0-0.51.41.4

[back to top]

Overall Survival (OS) in Modified Full Analysis Set (mFAS)

OS is defined as the time from randomization to the date of death, regardless of the actual cause of the participant's death. The participants who were still alive at the time of data analysis or who were lost to follow-up OS time was censored at the last recorded date that the participant was known to be alive before the data cutoff date. OS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Weekly15.4
Chemotherapy14.8

[back to top]

Number of Participants With At Least One Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab

Serum samples were analyzed by a validated electrochemiluminesce immunoassay to detect the presence of antidrug antibodies (ADA). Samples that screened positive were subsequently tested in a confirmatory assay were tested for neutralizing antibodies (nAb). Number of participants with ADA or nAb positive results for Avelumab were reported. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,
InterventionParticipants (Count of Participants)
ADAs to AvelumabNAbs to Avelumab
Avelumab Biweekly6643
Avelumab Weekly3818

[back to top]

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score Versus (Vs) Worst Post-baseline Score

ECOG performance status measured to assess participant's performance status on a scale of 0 to 5, where 0 = Fully active, able to carry on all pre-disease activities without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out light or sedentary work; 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; 3 = Capable of only limited self-care, confined to bed/chair for more than 50 percent of waking hours; 4 = Completely disabled, cannot carry on any self-care, totally confined to bed/chair; 5 = dead. ECOG performance status was reported in terms of number of participants with baseline value vs worst post-baseline value (that is [i.e.] highest score). (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
Baseline score 0, worst post-baseline score 0Baseline score 0, worst post-baseline score 1Baseline score 0, worst post-baseline score 2Baseline score 0, worst post-baseline score 3Baseline score 0, worst post-baseline score 4Baseline score 0, worst post-baseline score 5Baseline score 0, worst post-baseline score MissingBaseline score 1, worst post-baseline score 0Baseline score 1, worst post-baseline score 1Baseline score 1, worst post-baseline score 2Baseline score 1, worst post-baseline score 3Baseline score 1, worst post-baseline score 4Baseline score 1, worst post-baseline score 5Baseline score 1, worst post-baseline score MissingBaseline score >=2, worst post-baseline score 0Baseline score >=2, worst post-baseline score 1Baseline score >=2, worst post-baseline score 2Baseline score >=2, worst post-baseline score 3Baseline score >=2, worst post-baseline score 4Baseline score >=2, worst post-baseline score 5Baseline score >=2, worst post-baseline score missingBaseline score missing, worst post-baseline score 0Baseline score missing, worst post-baseline score 1Baseline score missing, worst post-baseline score 2Baseline score missing, worst post-baseline score 3Baseline score missing, worst post-baseline score 4Baseline score missing, worst post-baseline score 5Baseline score missing, worst post-baseline score missing
Avelumab Biweekly50568110611683516351000010000000000
Avelumab Weekly3549970042153321811600000100000000
Chemotherapy84831140144233466431600000000100000

[back to top]

Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Body Temperature Increase

The number of participants with changes from baseline in increased Body Temperature (degree Celsius [°C]) were reported by using criteria: Baseline temperature (temp.) less than (<) 37°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C, greater than or equal to (>=)3°C and missing; Baseline temp. 37 - <38°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C, >=3°C and missing; Baseline temp. 38 - <39°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C, >=3°C and missing; Baseline temp. 39-<40°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C, >=3°C and missing; Baseline temp. >=40°C, on treatment change <1°C, 1 - <2°C, 2 - <3°C, >=3°C and missing; Baseline temp. missing, on treatment change missing. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
Baseline temp. <37°C, on treatment change <1°CBaseline temp.<37°C, on treatment change 1 - <2°CBaseline temp. <37°C, on treatment change 2 - <3°CBaseline temp. <37°C, on treatment change >=3°CBaseline temp. <37°C, on treatment change missingBaseline temp. 37 - <38°C, on treatment change <1°CBaseline temp. 37 - <38°C, on treatment change 1 - <2°CBaseline temp. 37 - <38°C, on treatment change 2 - <3°CBaseline temp. 37 - <38°C, on treatment change >=3°CBaseline temp. 37 - <38°C, on treatment change missingBaseline temp. 38 - <39°C, on treatment change <1°CBaseline temp. 38 - <39°C, on treatment change 1 - <2°CBaseline temp. 38 - <39°C, on treatment change 2 - <3°CBaseline temp. 38 - <39°C, on treatment change >=3°CBaseline temp. 38 - <39°C, on treatment change missingBaseline temp. 39 - <40°C, on treatment change <1°CBaseline temp. 39 - <40°C, on treatment change 1 - <2°CBaseline temp. 39 - <40°C, on treatment change 2 - <3°CBaseline temp. 39 - <40°C, on treatment change >=3°CBaseline temp. 39 - <40°C, on treatment change missingBaseline temp. >=40°C, on treatment change <1°CBaseline temp. >=40°C, on treatment change 1 - <2°CBaseline temp. >=40°C, on treatment change 2 - <3°CBaseline temp. >=40°C, on treatment change >=3°CBaseline temp. >=40°C, on treatment change missingBaseline temp. missing, on treatment change missing
Avelumab Biweekly2714530162310010000010000000000
Avelumab Weekly256322161920000000000000000000
Chemotherapy4033300213710030000000000000002

[back to top]

Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Independent Review Committee (IRC) in Moderate and High Programmed Death Ligand 1 (PD-L1)+ Modified Full Analysis Set (mFAS)

PFS is defined as the time from date of randomization until date of the first documentation of progressive disease (PD) or death due to any cause in the absence of documented PD, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the sum of the longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

Interventionmonths (Median)
Avelumab Weekly5.6
Chemotherapy5.6

[back to top]

Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) at End of Treatment (EOT) in High Programmed Death Ligand 1 (PD-L1)+ HRQoL Analysis Set

EORTC QLQ-LC13 consisted of 13 questions relating to disease symptoms specific to lung cancer and treatment side effects typical of treatment with chemotherapy and radiotherapy. The EORTC QLQ-LC13 module generated one multiple-item score assessing dyspnea and a series of single item scores assessing coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arms or shoulder and pain in other parts. Score range: 0 (no burden of symptom domain or single symptom item) to 100 (highest burden of symptoms for symptom domains and single items). (NCT02576574)
Timeframe: Baseline, End of treatment (up to Week 283.9)

,
Interventionscore on a scale (Mean)
DyspneaCoughingHemoptysisSore mouthDysphagiaPeripheral neuropathyAlopeciaPain in chestPain in arm or shoulderPain in other parts
Avelumab Biweekly7.32.4-1.83.03.03.60.0-4.20.61.8
Chemotherapy5.2-4.31.51.9-0.610.814.2-1.51.91.5

[back to top]

Number of Participants With Maximal On-Treatment Changes From Baseline in Vital Signs - Maximal Heart Rate Increase/Decrease

The number of participants with maximal on-treatment (TR) changes from baseline (BS) in Increase (Ic.)/Decrease (Dc.) heart rate (HR) (beats per minute [bpm]) were reported by using criteria: Ic./Dc. BS HR <100/>=100 bpm, on treatment change =<20 bpm, >20 - =<40 bpm, >40 bpm and missing; Ic./Dc. BS HR missing, on treatment change missing. (NCT02576574)
Timeframe: Time from date of randomization up to data cutoff (assessed up to approximately 71.5 months)

,,
InterventionParticipants (Count of Participants)
Ic. BS HR <100 bpm, on TR change =<20 bpmIc. BS HR <100 bpm, on TR change >20 - =<40 bpmIc. BS HR <100 bpm, on TR change >40 bpmIc. BS HR <100 bpm, on TR change missingIc. BS HR >= 100 bpm, on TR change =<20 bpmIc. BS HR >= 100 bpm, on TR change >20 - =<40 bpmIc. BS HR >= 100 bpm, on TR change >40 bpmIc. BS HR >= 100 bpm, on TR change missingIc. BS HR missing, on TR change missingDc. BS HR <100 bpm, on TR change =<20 bpmDc. BS HR <100 bpm, on TR change >20 - =<40 bpmDc. BS HR <100 bpm, on TR change >40 bpmDc. BS HR <100 bpm, on TR change missingDc. BS HR >= 100 bpm, on TR change =<20 bpmDc. BS HR >= 100 bpm, on TR change >20 - =<40 bpmDc. BS HR >= 100 bpm, on TR change >40 bpmDc. BS HR >= 100 bpm, on TR change missingDc. BS HR missing, on TR change missing
Avelumab Biweekly206862114310030267442141461130
Avelumab Weekly2026612530201022752151312710
Chemotherapy33285916463072385401162026372

[back to top]

Progression-free Survival (PFS) of Subjects With Advanced Nasopharyngeal Carcinoma.

Progression-free survival was defined as the duration from randomization to the first occurrence of documented disease progression [based on imaging results] or death from any cause, whichever occurred first. (NCT02578641)
Timeframe: From randomization until first occurrence of disease progression or death of any cause, whichever occurred first, assessed up to 7 years. Subjects who received subsequent anti-cancer therapy were censored at the date of last tumor assessment.

InterventionMonths (Median)
Chemo + EBV-CTL7.9
Chemo Only8.5

[back to top]

Overall Survival (OS) of Subjects With Advanced Nasopharyngeal Carcinoma.

Efficacy of EBV-CTL following first line chemotherapy was compared to chemotherapy alone in terms of OS of subjects with advanced nasopharyngeal carcinoma. Overall survival was defined as the duration in months from the day of randomization until death from any cause for a subject known to be deceased, or censored at the last contact date that a subject was known to be alive or lost to follow-up. (NCT02578641)
Timeframe: From randomization until death, assessed up to 7 years. Survivors and lost to follow-up subjects were censored at the date of last contact. Survival follow-up was done every 12 weeks from end of treatment.

InterventionMonths (Median)
Chemo + EBV-CTL25
Chemo Only24.9

[back to top]

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS is presented. (NCT02578680)
Timeframe: Through Database Cutoff Date of 08-Nov-2017 (Up to approximately 21 months)

InterventionMonths (Median)
PembrolizumabNA
Control11.3

[back to top]

Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. (NCT02578680)
Timeframe: From time of first documented evidence of CR or PR through database cutoff date of 08-Nov-2017 (Up to approximately 21 months)

InterventionMonths (Median)
Pembrolizumab11.2
Control7.8

[back to top]

Number of Participants Who Discontinued Any Study Drug Due to an AE

The number of participants who discontinued any randomized study drug due to an AE is presented. (NCT02578680)
Timeframe: Through Database Cutoff Date of 08-Nov-2017 (Up to approximately 21 months)

InterventionParticipants (Count of Participants)
Pembrolizumab112
Control30

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a study participant administered study drug and which does not necessarily have to have a causal relationship with this study drug. For participants who switched from the Control group to receiving pembro, AEs that occurred after the first dose of pembro are excluded from this interim analysis, but will be included in the final analysis. The number of participants who experienced an AE is presented. (NCT02578680)
Timeframe: Through Database Cutoff Date of 08-Nov-2017 (Up to approximately 21 months); Serious AEs: Up to 90 days after last dose of study treatment, Other AEs: Up to 30 days after last dose of study treatment

InterventionParticipants (Count of Participants)
Pembrolizumab404
Control200

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented. (NCT02578680)
Timeframe: Through Database Cutoff Date of 08-Nov-2017 (Up to approximately 21 months)

InterventionMonths (Median)
Pembrolizumab8.8
Control4.9

[back to top]

Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. (NCT02578680)
Timeframe: Through Database Cutoff Date of 08-Nov-2017 (Up to approximately 21 months)

InterventionPercentage of Participants (Number)
Pembrolizumab47.6
Control18.9

[back to top]

Symptom Assessment (Measured by FACT-L Symptom Assessment Scale)

The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. A maximum score of 136 could be obtained. (NCT02590003)
Timeframe: baseline

Interventionunits on a scale (Mean)
Platinum-based Doublet Chemotherapy89
Single Agent Chemotherapy44

[back to top]

Symptom Assessment (Measured by FACT-L Symptom Assessment Scale)

The higher the score, the greater the symptoms. The FACT-L is measure of symptoms associated with lung cancer. The higher the score, the greater the symptoms. A maximum score of 136 could be obtained. Symptoms were measured following 2 21-day cycles of chemotherapy. (NCT02590003)
Timeframe: week 6

Interventionunits on a scale (Mean)
Single Agent Chemotherapy60.5

[back to top]

Treatment Failure-free Survival

(NCT02590003)
Timeframe: 90 days

InterventionParticipants (Count of Participants)
Platinum-based Doublet Chemotherapy0
Single Agent Chemotherapy0

[back to top]

Grade 3-5 Adverse Events

Adverse events were characterized using Common Terminology Criteria for Adverse Events (CTCAE) (NCT02590003)
Timeframe: Up to week 13

,
InterventionParticipants (Count of Participants)
OverallGrade 3Grade 4Grade 5
Platinum-based Doublet Chemotherapy0000
Single Agent Chemotherapy2200

[back to top]

Overall Response Rate

(NCT02590003)
Timeframe: start of treatment to disease progression/recurrence, up to 12 months

InterventionParticipants (Count of Participants)
Platinum-based Doublet Chemotherapy0
Single Agent Chemotherapy0

[back to top]

Overall Survival

(NCT02590003)
Timeframe: Up to 12 months

InterventionParticipants (Count of Participants)
Platinum-based Doublet Chemotherapy0
Single Agent Chemotherapy0

[back to top]

Progression-free Survival

(NCT02590003)
Timeframe: start of treatment to disease progression, up to 12 months

InterventionParticipants (Count of Participants)
Platinum-based Doublet Chemotherapy0
Single Agent Chemotherapy0

[back to top]

Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)

To characterize the adverse events related to MK-3475 by frequency, type and grade in patients with Chemotherapy naive advanced NSCLC based on the sequence of administration with first-line chemotherapy. A count of participants experiencing an adverse event is summarized here, the detailed summary is in the adverse events section of this report. (NCT02591615)
Timeframe: 24 Months

Interventionparticipants (Number)
Arm A Squamous Carcinoma9
Arm A Non-squamous Carcinoma34
Arm B Squamous Carcinoma10
Arm B Non-squamous Carcinoma37

[back to top]

Overall Response Rate (ORR) Per RECIST 1.1

The primary objective of this randomized phase II trial to determine the overall response rate (ORR per RECIST 1.1) in Chemotherapy naive patients with stage IV NSCLC after the administration of standard platinum-based chemotherapy before MK-3475 (arm A) and administration of MK-3475 administered before standard platinum-based chemotherapy (arm B). Overall Response (OR) = CR + PR. (NCT02591615)
Timeframe: 18 Months

Interventionproportion of participants (Number)
Arm A (Both Squamous and Non-Squamous)0.395
Arm B (Both Squamous and Non-Squamous)0.404

[back to top]

Compare Progression-Free Survival (PFS) Per RECIST 1.1

To compare the progression-free survival (PFS) per RECIST 1.1 in previously untreated patients with advanced NSCLC treated with first line carboplatin-based chemotherapy followed by MK-3475 to patients treated with MK-3475 prior to first-line carboplatin-based chemotherapy. (NCT02591615)
Timeframe: 24 Months

InterventionMonths (Median)
Arm A (Both Squamous and Non-Squamous)5.8
Arm B (Both Squamous and Non-Squamous)4.0

[back to top]

Complete Remission Rate Per Independent Review Facility

Number of patients with complete metabolic response by PET (positive emission tomography) and CT (computed tomography) scans, or complete radiologic response by CT only. (NCT02592876)
Timeframe: Up to 4 months

InterventionParticipants (Count of Participants)
RICE18
19A+RICE25

[back to top]

Progression-free Survival (PFS)

PFS is defined as the time from randomization to first documentation of disease progression per investigator, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first. (NCT02592876)
Timeframe: Up to 30 months

Interventionmonths (Median)
RICENA
19A+RICENA

[back to top]

Duration of Complete Response (CR)

Defined as the time from the start of the first radiographic documentation of CR per investigator to the first documentation of progressive disease, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first. (NCT02592876)
Timeframe: Up to 27.9 months

Interventionmonths (Median)
RICENA
19A+RICENA

[back to top]

Duration of Objective Response (OR)

Duration of OR is defined as the time from the start of the first radiographic documentation of OR per investigator to the first documentation of PD, death due to any cause, or receipt of subsequent anticancer therapy, whichever comes first. (NCT02592876)
Timeframe: Up to 27.9 months

Interventionmonths (Median)
RICENA
19A+RICENA

[back to top]

Objective Response Rate (ORR)

ORR is defined as the proportion of patients with complete remission (CR) or partial remission (PR) per independent review facility (IRF) at the end of treatment. (NCT02592876)
Timeframe: Up to 4 months

InterventionParticipants (Count of Participants)
RICE30
19A+RICE32

[back to top]

Overall Survival (OS)

OS is defined as the time from date of randomization to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the patient is known to be alive. (NCT02592876)
Timeframe: Up to 30 months

Interventionmonths (Median)
RICENA
19A+RICENA

[back to top]

Number of Participants With Adverse Events (AEs)

Treatment-emergent adverse events (TEAEs) are presented and defined as newly occurring (not present at baseline) or worsening after first dose of investigational product. AE severity and seriousness are assessed independently. 'Severity' characterizes the intensity of an AE and is graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.03. An AE is considered 'serious' if it is life-threatening, fatal, requires hospitalization, or is otherwise considered to be medically significant. (NCT02592876)
Timeframe: Up to 4 months

,
InterventionParticipants (Count of Participants)
Treatment-emergent AE (TEAE)Treatment-related AEsGrade 3 or Higher TEAEsSerious AEs (SAEs)Treatment-related SAEsAEs Leading to Dose DelayAEs Leading to Dose ReductionAEs Leading to Treatment Discontinuation
19A+RICE4040381913853
RICE393831139332

[back to top]

Number of Participants With Laboratory Abnormalities

Number of participants who experienced a maximum post-baseline laboratory toxicity of Grade 3 or higher (per National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.03). (NCT02592876)
Timeframe: Up to 4 months

,
InterventionParticipants (Count of Participants)
Any Hematology TestHemoglobin LowLeukocytes HighLeukocytes LowLymphocytes HighLymphocytes LowNeutrophils LowPlatelets LowAny Chemistry TestAlanine Aminotransferase HighAspartate Aminotransferase HighCalcium HighCalcium LowCreatinine HighGlucose HighPhosphate LowPotassium LowSodium LowUrate High
19A+RICE37180240312235163202138530
RICE37191232342226183140049342

[back to top]

Number of Patients Achieving Peripheral Blood Stem Cell (PBSC) Mobilization

Defined as the number of patients who are able to adequately mobilize PBSC per investigator assessment on or after completion of study treatment, prior to subsequent anticancer therapy. (NCT02592876)
Timeframe: Up to 30 months

,
InterventionParticipants (Count of Participants)
Patients with attempted stem cell collection(s)Patients with sufficient stem cell collection
19A+RICE2421
RICE2826

[back to top]

Number of Patients Receiving Autologous Stem Cell Transplant (ASCT)

Number of patients receiving ASCT after completion of study treatment (EOT), prior to subsequent anticancer therapy. (NCT02592876)
Timeframe: Up to 30 months

,
InterventionParticipants (Count of Participants)
Patients planned to receive ASCT at EOTPatients who received ASCT at EOT
19A+RICE2522
RICE2825

[back to top]

Maximum Tolerated Dose (MTD) and Dose Limiting Toxicity (DLT) of the Combination of Pembrolizumab With Paclitaxel, Carboplatin and Radiation Therapy According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

The 3+3 algorithm design will be used to find the MTD. Safety will be evaluated by DLT, defined as grade 4 pneumonitis. Toxicities will be characterized based on seriousness, causality, toxicity grading, and action taken with regard to trial treatment. (NCT02621398)
Timeframe: Up to 30 days

Interventionmg (Number)
All Participants200

[back to top]

Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 (No Invasive Residual in Breast or Nodes; Noninvasive Breast Residuals Allowed)

pCR rate (ypT0/Tis ypN0; no invasive residual in breast or nodes; noninvasive breast residuals allowed) was defined as the rate of absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria assessed by local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the alternative definition of ypT0/Tis ypN0 is presented. (NCT02622074)
Timeframe: Up to approximately 9 months (at the time of definitive surgery)

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC60.0
Cohort B: KNpCb (Regimen 1) / KAC80.0
Cohort C: KNpCb (Regimen 2) / KAC80.0
Cohort D: KNpCb (Regimen 3) / KAC60.0
Cohort E: KTCb (Regimen 1) / KAC30.0
Cohort F: KTCb (Regimen 2) / KAC50.0

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: First Combination Regimen

ORR was defined as the percentage of participants who achieved a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions) according to RECIST 1.1 by Investigator review. Because imaging was assessed prior to surgery, a confirmation assessment of CR or PR was not obtained. Participants with missing outcome for objective response were considered non-responders. The percentage of participants who experienced a CR or PR based on RECIST 1.1 following the first combination regimen is presented. (NCT02622074)
Timeframe: At the end of Cycle 5 following treatment with the first combination regimen (KNp, KNpCb, or KTCb) (Up to ~4 months); Each cycle was 21 days.

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC60.0
Cohort B: KNpCb (Regimen 1) / KAC90.0
Cohort C: KNpCb (Regimen 2) / KAC90.0
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC60.0
Cohort F: KTCb (Regimen 2) / KAC80.0

[back to top]

Event-Free Survival (EFS) Rate at Month 6

EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 6 are presented (through Final Analysis cut-off of 18-Nov-2019). (NCT02622074)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC90.0
Cohort B: KNpCb (Regimen 1) / KAC100.0
Cohort C: KNpCb (Regimen 2) / KAC100.00
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC100.0
Cohort F: KTCb (Regimen 2) / KAC100.0

[back to top]

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented. (NCT02622074)
Timeframe: Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)

InterventionParticipants (Count of Participants)
Cohort A: KNp / KAC1
Cohort B: KNpCb (Regimen 1) / KAC2
Cohort C: KNpCb (Regimen 2) / KAC1
Cohort D: KNpCb (Regimen 3) / KAC5
Cohort E: KTCb (Regimen 1) / KAC2
Cohort F: KTCb (Regimen 2) / KAC5

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE either prior to or after definitive surgery is presented. (NCT02622074)
Timeframe: Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)

InterventionParticipants (Count of Participants)
Cohort A: KNp / KAC10
Cohort B: KNpCb (Regimen 1) / KAC10
Cohort C: KNpCb (Regimen 2) / KAC10
Cohort D: KNpCb (Regimen 3) / KAC10
Cohort E: KTCb (Regimen 1) / KAC10
Cohort F: KTCb (Regimen 2) / KAC10

[back to top]

Number of Participants With Dose Limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)

"The following events, if considered to be study-treatment-related by the Investigator, were considered a DLT:~Hematologic:~Grade 4 neutropenia lasting ≥8 days;~Febrile neutropenia Grade 3 or Grade 4; or~Grade 4 thrombocytopenia requiring platelet transfusion, or Grade 3 thrombocytopenia with bleeding~Non-hematologic:~Grade 4 toxicity;~Grade ≥3 symptomatic hepatic toxicities lasting >48 hours, or Grade ≥3 asymptomatic hepatic toxicities lasting ≥7 days; or~Grade ≥3 non-hematologic, non-hepatic organ toxicity, with exceptions~Other:~Any treatment delays for ≥14 days due to unresolved toxicity;~Grade 5 treatment-related adverse event (AE);~A dose reduction of study treatment during the DLT evaluation period." (NCT02622074)
Timeframe: Cycle 1 Day 1 through end of Cycle 3 and Cycle 6 Day 1 through end of Cycle 7 (Up to ~150 days from first dose of first combination regimen); Each cycle was 21 days.

InterventionParticipants (Count of Participants)
Cohort A: KNp / KAC2
Cohort B: KNpCb (Regimen 1) / KAC4
Cohort C: KNpCb (Regimen 2) / KAC6
Cohort D: KNpCb (Regimen 3) / KAC6
Cohort E: KTCb (Regimen 1) / KAC0
Cohort F: KTCb (Regimen 2) / KAC4

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: Second Combination Regimen

ORR was defined as the percentage of participants who achieved a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions) according to RECIST 1.1 by Investigator review. Because imaging was assessed prior to surgery, a confirmation assessment of CR or PR was not obtained. Participants with missing outcome for objective response were considered non-responders. The percentage of participants who experienced a CR or PR based on RECIST 1.1 following the second combination regimen is presented. (NCT02622074)
Timeframe: After completion of the second combination regimen (KAC; Cycle 9) but prior to surgery (Up to ~9 months); Each cycle was 21 days.

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC80.0
Cohort B: KNpCb (Regimen 1) / KAC100
Cohort C: KNpCb (Regimen 2) / KAC100
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC70.0
Cohort F: KTCb (Regimen 2) / KAC90.0

[back to top]

Overall Survival (OS) Rate at Month 12

OS was defined as the time from the first dose date of study treatment to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 12 are presented (through Final Analysis cut-off of 18-Nov-2019). (NCT02622074)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC80.0
Cohort B: KNpCb (Regimen 1) / KAC100.0
Cohort C: KNpCb (Regimen 2) / KAC100.0
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC100.0
Cohort F: KTCb (Regimen 2) / KAC100.0

[back to top]

Event-Free Survival (EFS) Rate at Month 12

EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 12 are presented (through Final Analysis cut-off of 18-Nov-2019). (NCT02622074)
Timeframe: Month 12

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC80.0
Cohort B: KNpCb (Regimen 1) / KAC100.0
Cohort C: KNpCb (Regimen 2) / KAC100.0
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC100.0
Cohort F: KTCb (Regimen 2) / KAC100.0

[back to top]

Event-Free Survival (EFS) Rate at Month 24

EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 24 are presented (through Final Analysis cut-off of 18-Nov-2019). (NCT02622074)
Timeframe: Month 24

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC60.0
Cohort B: KNpCb (Regimen 1) / KAC100.0
Cohort C: KNpCb (Regimen 2) / KAC100.0
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC90.0
Cohort F: KTCb (Regimen 2) / KAC100.0

[back to top]

Overall Survival (OS) Rate at Month 6

OS was defined as the time from the first dose date of study treatment to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 6 are presented (through Final Analysis cut-off of 18-Nov-2019). (NCT02622074)
Timeframe: Month 6

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC100.0
Cohort B: KNpCb (Regimen 1) / KAC100.0
Cohort C: KNpCb (Regimen 2) / KAC100.0
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC100.0
Cohort F: KTCb (Regimen 2) / KAC100.0

[back to top]

Overall Survival (OS) Rate at Month 24

OS was defined as the time from the first dose date of study treatment to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 24 are presented (through Final Analysis cut-off of 18-Nov-2019). (NCT02622074)
Timeframe: Month 24

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC70.0
Cohort B: KNpCb (Regimen 1) / KAC100.0
Cohort C: KNpCb (Regimen 2) / KAC100.0
Cohort D: KNpCb (Regimen 3) / KAC90.0
Cohort E: KTCb (Regimen 1) / KAC90.0
Cohort F: KTCb (Regimen 2) / KAC100.0

[back to top]

Pathological Complete Response (pCR) Rate Using the Definition of ypT0 ypN0 (No Invasive or Noninvasive Residual in Breast or Nodes)

pCR rate (ypT0 ypN0; no invasive or noninvasive residual in breast or nodes) was defined as the rate of absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by American Joint Committee on Cancer (AJCC) staging criteria assessed by local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the definition of ypT0 ypN0 is presented. (NCT02622074)
Timeframe: Up to approximately 9 months (at the time of definitive surgery)

InterventionPercentage of Participants (Number)
Cohort A: KNp / KAC50.0
Cohort B: KNpCb (Regimen 1) / KAC80.0
Cohort C: KNpCb (Regimen 2) / KAC80.0
Cohort D: KNpCb (Regimen 3) / KAC60.0
Cohort E: KTCb (Regimen 1) / KAC20.0
Cohort F: KTCb (Regimen 2) / KAC50.0

[back to top]

Progression Free Survival (PFS) in the Heregulin (HRG)-High Expression Population

"PFS is defined as the time from the date of randomization to the date of the first radiographic disease progression or death due to any cause, whichever comes first.~Median PFS is from Kaplan-Meier analysis. Confidence interval (CI) for median was computed using Brookmeyer-Crowley method." (NCT02633800)
Timeframe: from Day 0 to end of active study (study termination) - within 12 months

Interventionmonths (Median)
Patritumab5.56
Placebo5.56

[back to top]

Plasma Concentrations for Cisplatin in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)

(NCT02657434)
Timeframe: Prd (0 h), 5-10 mins before end of cisplatin infusion (infusion duration=30-60 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)

Interventionng/mL (Mean)
Cy1D1 PredoseCy1D1 Before End of InfusionCy1D1 Post InfusionCy3D1 PredoseCy3D1 Before End of InfusionCy3D1 Post Infusion
Arm A (Atezolizumab + Carboplatin or Cisplatin + PemetrexedNA3630240029030202740

[back to top]

Plasma Concentrations for Pemetrexed in Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)

(NCT02657434)
Timeframe: Prd (0 h), 5-10 mins before end of pemetrexed infusion (infusion duration=10 mins), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)

Interventionng/mL (Mean)
Cy1D1 PredoseCy1D1 Before End of InfusionCy1D1 Post InfusionCy3D1 PredoseCy3D1 Before End of InufsionCy3D1 Post Infusion
Arm A (Atezolizumab + Carboplatin or Cisplatin + PemetrexedNA86500436001.837940050100

[back to top]

Plasma Concentrations for Carboplatin in Arm A(Atezolizumab + Carboplatin or Cisplatin + Pemetrexed)

(NCT02657434)
Timeframe: Prd (0 h), 5-10 minutes (mins) before end of carboplatin infusion (infusion duration=1-2 h), 1 h post-infusion on D1 of Cy1,3 (Cy length=21 days)

Interventionng/mL (Mean)
Cy1D1 PredoseCy1D1 Before End of InfusionCy1D1 Post InfusionCy3D1 PredoseCy3D1 Before End of InfusionCy3D1 Post Infusion
Arm A (Atezolizumab + Carboplatin or Cisplatin + PemetrexedNA14900128002201790013900

[back to top]

Duration of Response (DOR) as Determined by the Investigator Using RECIST v1.1

DOR is defined as the time interval from the date of the first occurrence of a CR or PR (whichever status is recorded first) until the first date that progressive disease or death is documented, whichever occurs first. (NCT02657434)
Timeframe: Randomization up to approximately 25 months

InterventionMonths (Number)
Arm B (Carboplatin or Cisplatin + Pemetrexed)6.4
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed9.5

[back to top]

Maximum Observed Serum Atezolizumab Concentration (Cmax)

Maximum observed serum atezolizumab concentration (Cmax) after infusion (Arm A) (NCT02657434)
Timeframe: Day 1 of Cycle 1 (Cycle length=21 days)

Interventionμg/mL (Mean)
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed403

[back to top]

Overall Survival (OS)

OS is defined as time from randomization to death from any cause. (NCT02657434)
Timeframe: Randomization up to approximately 39 months

InterventionMonths (Median)
Arm B (Carboplatin or Cisplatin + Pemetrexed)13.6
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed17.5

[back to top]

Overall Survival Rate at Year 1

The Overall Survival Rate at the 1-year landmark time point is defined as the probabilities that participants are alive 1-year after randomization. (NCT02657434)
Timeframe: Year 1

InterventionPercentage (Number)
Arm B (Carboplatin or Cisplatin + Pemetrexed)55.04
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed59.72

[back to top]

Overall Survival Rate Year 2

The Overall Survival Rate at the 2-year landmark time point is defined as the probabilities that participants are alive 2-years after randomization. (NCT02657434)
Timeframe: Year 2

InterventionPercentage (Number)
Arm B (Carboplatin or Cisplatin + Pemetrexed)34.01
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed39.13

[back to top]

Progression Free Survival (PFS) as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

PFS is defined as the time from randomization to the first occurrence of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever occurred first. (NCT02657434)
Timeframe: Randomization up to approximately 39 months

InterventionMonths (Median)
Arm B (Carboplatin or Cisplatin + Pemetrexed)5.2
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed7.7

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score

The EORTC QLQ-LC13 module incorporates one multiple item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998). (NCT02657434)
Timeframe: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)

InterventionUnits on a scale (Mean)
Coughing: Week 3Coughing: Week 6Coughing: Week 9Coughing: Week 12Coughing: Week 15Coughing: Week 18Coughing: Week 21Coughing: Week 24Coughing: Week 27Coughing: Week 30Coughing: Week 33Coughing: Week 36Coughing: Week 39Coughing: Week 42Coughing: Week 45Coughing: Week 48Coughing: Week 51Coughing: Week 54Coughing: Week 57Coughing: Week 60Coughing: Week 63Coughing: Week 66Coughing: Week 69Coughing: Week 72Coughing: Week 75Coughing: Week 78Coughing: Week 81Coughing: Week 84Coughing: Week 87Coughing: Week 90Coughing: Time of First PdCoughing: Time of Last Tx DoseCoughing: Survival Follow-Up Week 12Coughing: Survival Follow-Up Week 24Dyspnoea: Week 3Dyspnoea: Week 6Dyspnoea: Week 9Dyspnoea: Week 12Dyspnoea: Week 15Dyspnoea: Week 18Dyspnoea: Week 21Dyspnoea: Week 24Dyspnoea: Week 27Dyspnoea: Week 30Dyspnoea: Week 33Dyspnoea: Week 36Dyspnoea: Week 39Dyspnoea: Week 42Dyspnoea: Week 45Dyspnoea: Week 48Dyspnoea: Week 51Dyspnoea: Week 54Dyspnoea: Week 57Dyspnoea: Week 60Dyspnoea: Week 63Dyspnoea: Week 66Dyspnoea: Week 69Dyspnoea: Week 72Dyspnoea: Week 75Dyspnoea: Week 78Dyspnoea: Week 81Dyspnoea: Week 84Dyspnoea: Week 87Dyspnoea: Week 90Dyspnoea: Time of First PDDyspnoea: Time of Last Tx DoseDyspnoea: Survival Follow-Up Week 12Dyspnoea: Survival Follow-Up Week 24Pain In Chest: Week 3Pain In Chest: Week 6Pain In Chest: Week 9Pain In Chest: Week 12Pain In Chest: Week 15Pain In Chest: Week 18Pain In Chest: Week 21Pain In Chest: Week 24Pain In Chest: Week 27Pain In Chest: Week 30Pain In Chest: Week 33Pain In Chest: Week 36Pain In Chest: Week 39Pain In Chest: Week 42Pain In Chest: Week 45Pain In Chest: Week 48Pain In Chest: Week 51Pain In Chest: Week 54Pain In Chest: Week 57Pain In Chest: Week 60Pain In Chest: Week 63Pain In Chest: Week 66Pain In Chest: Week 69Pain In Chest: Week 72Pain In Chest: Week 75Pain In Chest: Week 78Pain In Chest: Week 81Pain In Chest: Week 84Pain In Chest: Week 87Pain In Chest: Week 90Pain In Chest: Time of First PdPain In Chest: Time of Last Tx DosePain In Chest: Survival Follow-Up Week 12Pain In Chest: Survival Follow-Up Week 24Pain In Arm Or Shoulder: Week 3Pain In Arm Or Shoulder: Week 6Pain In Arm Or Shoulder: Week 9Pain In Arm Or Shoulder: Week 12Pain In Arm Or Shoulder: Week 15Pain In Arm Or Shoulder: Week 18Pain In Arm Or Shoulder: Week 21Pain In Arm Or Shoulder: Week 24Pain In Arm Or Shoulder: Week 27Pain In Arm Or Shoulder: Week 30Pain In Arm Or Shoulder: Week 33Pain In Arm Or Shoulder: Week 36Pain In Arm Or Shoulder: Week 39Pain In Arm Or Shoulder: Week 42Pain In Arm Or Shoulder: Week 45Pain In Arm Or Shoulder: Week 48Pain In Arm Or Shoulder: Week 51Pain In Arm Or Shoulder: Week 54Pain In Arm Or Shoulder: Week 57Pain In Arm Or Shoulder: Week 60Pain In Arm Or Shoulder: Week 63Pain In Arm Or Shoulder: Week 66Pain In Arm Or Shoulder: Week 69Pain In Arm Or Shoulder: Week 72Pain In Arm Or Shoulder: Week 75Pain In Arm Or Shoulder: Week 78Pain In Arm Or Shoulder: Week 81Pain In Arm Or Shoulder: Week 84Pain In Arm Or Shoulder: Week 87Pain In Arm Or Shoulder: Week 90Pain In Arm Or Shoulder: Time of First PdPain In Arm Or Shoulder: Time of Last Tx DosePain In Arm Or Shoulder:Survival Follow-Up Week 12Pain In Arm Or Shoulder:Survival Follow-Up Week 24
Arm B (Carboplatin or Cisplatin + Pemetrexed)-2.50-3.57-1.85-3.91-6.33-4.00-6.00-4.81-3.850.42-0.46-6.11-5.00-8.97-13.19-7.69-17.59-17.20-11.54-14.04-10.26-9.52-11.11-8.33-13.33-16.67-16.67-33.330.00-33.33-6.01-5.193.57-8.770.210.120.891.150.00-1.07-3.56-2.29-0.711.250.77-1.111.30-0.43-2.08-4.56-9.88-6.45-2.99-11.11-6.84-9.52-16.67-5.56-6.670.0011.110.000.000.002.373.969.924.68-1.250.710.82-2.07-1.46-3.47-3.33-2.41-5.13-4.17-0.46-1.67-3.89-7.69-6.25-7.69-11.11-7.53-1.280.00-5.13-4.76-16.67-8.33-6.670.000.000.00-33.33-33.336.561.345.951.75-4.69-4.46-2.88-6.90-3.89-5.07-6.00-2.41-5.561.25-5.56-1.67-5.000.00-0.69-1.71-2.78-1.08-1.28-5.26-5.134.760.00-8.33-6.670.000.000.000.000.002.19-0.5013.101.75

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC Quality-of-Life Lung Cancer Module (QLQ-LC13) Symptom Score

The EORTC QLQ-LC13 module incorporates one multiple item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. The EORTC QLQ-LC13 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however, a high score for a symptom scale or item represents a high level of symptomatology or problems. A≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998). (NCT02657434)
Timeframe: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)

InterventionUnits on a scale (Mean)
Coughing: Week 3Coughing: Week 6Coughing: Week 9Coughing: Week 12Coughing: Week 15Coughing: Week 18Coughing: Week 21Coughing: Week 24Coughing: Week 27Coughing: Week 30Coughing: Week 33Coughing: Week 36Coughing: Week 39Coughing: Week 42Coughing: Week 45Coughing: Week 48Coughing: Week 51Coughing: Week 54Coughing: Week 57Coughing: Week 60Coughing: Week 63Coughing: Week 66Coughing: Week 69Coughing: Week 72Coughing: Week 75Coughing: Week 78Coughing: Week 81Coughing: Week 84Coughing: Week 87Coughing: Week 90Coughing: Week 93Coughing: Time of First PdCoughing: Time of Last Tx DoseCoughing: Survival Follow-Up Week 12Coughing: Survival Follow-Up Week 24Dyspnoea: Week 3Dyspnoea: Week 6Dyspnoea: Week 9Dyspnoea: Week 12Dyspnoea: Week 15Dyspnoea: Week 18Dyspnoea: Week 21Dyspnoea: Week 24Dyspnoea: Week 27Dyspnoea: Week 30Dyspnoea: Week 33Dyspnoea: Week 36Dyspnoea: Week 39Dyspnoea: Week 42Dyspnoea: Week 45Dyspnoea: Week 48Dyspnoea: Week 51Dyspnoea: Week 54Dyspnoea: Week 57Dyspnoea: Week 60Dyspnoea: Week 63Dyspnoea: Week 66Dyspnoea: Week 69Dyspnoea: Week 72Dyspnoea: Week 75Dyspnoea: Week 78Dyspnoea: Week 81Dyspnoea: Week 84Dyspnoea: Week 87Dyspnoea: Week 90Dyspnoea: Week 93Dyspnoea: Time of First PDDyspnoea: Time of Last Tx DoseDyspnoea: Survival Follow-Up Week 12Dyspnoea: Survival Follow-Up Week 24Pain In Chest: Week 3Pain In Chest: Week 6Pain In Chest: Week 9Pain In Chest: Week 12Pain In Chest: Week 15Pain In Chest: Week 18Pain In Chest: Week 21Pain In Chest: Week 24Pain In Chest: Week 27Pain In Chest: Week 30Pain In Chest: Week 33Pain In Chest: Week 36Pain In Chest: Week 39Pain In Chest: Week 42Pain In Chest: Week 45Pain In Chest: Week 48Pain In Chest: Week 51Pain In Chest: Week 54Pain In Chest: Week 57Pain In Chest: Week 60Pain In Chest: Week 63Pain In Chest: Week 66Pain In Chest: Week 69Pain In Chest: Week 72Pain In Chest: Week 75Pain In Chest: Week 78Pain In Chest: Week 81Pain In Chest: Week 84Pain In Chest: Week 87Pain In Chest: Week 90Pain In Chest: Week 93Pain In Chest: Time of First PdPain In Chest: Time of Last Tx DosePain In Chest: Survival Follow-Up Week 12Pain In Chest: Survival Follow-Up Week 24Pain In Arm Or Shoulder: Week 3Pain In Arm Or Shoulder: Week 6Pain In Arm Or Shoulder: Week 9Pain In Arm Or Shoulder: Week 12Pain In Arm Or Shoulder: Week 15Pain In Arm Or Shoulder: Week 18Pain In Arm Or Shoulder: Week 21Pain In Arm Or Shoulder: Week 24Pain In Arm Or Shoulder: Week 27Pain In Arm Or Shoulder: Week 30Pain In Arm Or Shoulder: Week 33Pain In Arm Or Shoulder: Week 36Pain In Arm Or Shoulder: Week 39Pain In Arm Or Shoulder: Week 42Pain In Arm Or Shoulder: Week 45Pain In Arm Or Shoulder: Week 48Pain In Arm Or Shoulder: Week 51Pain In Arm Or Shoulder: Week 54Pain In Arm Or Shoulder: Week 57Pain In Arm Or Shoulder: Week 60Pain In Arm Or Shoulder: Week 63Pain In Arm Or Shoulder: Week 66Pain In Arm Or Shoulder: Week 69Pain In Arm Or Shoulder: Week 72Pain In Arm Or Shoulder: Week 75Pain In Arm Or Shoulder: Week 78Pain In Arm Or Shoulder: Week 81Pain In Arm Or Shoulder: Week 84Pain In Arm Or Shoulder: Week 87Pain In Arm Or Shoulder: Week 90Pain In Arm Or Shoulder: Week 93Pain In Arm Or Shoulder: Time of First PdPain In Arm Or Shoulder: Time of Last Tx DosePain In Arm Or Shoulder:Survival Follow-Up Week 12Pain In Arm Or Shoulder:Survival Follow-Up Week 24
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed-3.41-9.82-8.29-10.71-11.53-11.63-10.50-10.03-11.65-11.39-11.97-12.94-13.41-14.70-14.72-13.92-10.97-13.81-13.53-10.71-12.82-12.61-11.90-16.67-18.84-23.81-18.52-29.17-25.00-16.670.00-10.48-8.13-6.94-14.29-1.41-1.17-3.34-0.46-1.12-3.88-1.45-0.42-2.08-2.78-3.02-2.91-4.95-6.33-3.61-5.34-1.69-1.90-4.99-0.40-6.55-4.50-4.76-1.52-6.76-3.17-9.88-6.94-2.785.5622.22-0.160.4413.434.760.81-6.32-4.24-0.60-3.56-3.36-2.74-4.76-2.71-3.06-3.88-2.91-3.99-7.17-5.63-4.64-5.49-4.29-5.80-3.57-6.84-4.50-5.95-4.550.000.007.414.178.330.000.00-3.81-0.83-2.78-4.76-2.60-5.44-8.09-4.37-7.34-6.26-1.83-5.26-3.79-3.33-1.94-3.24-3.99-8.60-6.06-4.22-3.38-6.19-2.90-4.17-3.42-1.80-7.14-7.58-8.70-2.383.704.17-16.670.000.001.900.335.560.00

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score

EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998). (NCT02657434)
Timeframe: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)

InterventionUnits on a scale (Mean)
Dyspnoea: Week 3Dyspnoea: Week 6Dyspnoea: Week 9Dyspnoea: Week 12Dyspnoea: Week 15Dyspnoea: Week 18Dyspnoea: Week 21Dyspnoea: Week 24Dyspnoea: Week 27Dyspnoea: Week 30Dyspnoea: Week 33Dyspnoea: Week 36Dyspnoea: Week 39Dyspnoea: Week 42Dyspnoea: Week 45Dyspnoea: Week 48Dyspnoea: Week 51Dyspnoea: Week 54Dyspnoea: Week 57Dyspnoea: Week 60Dyspnoea: Week 63Dyspnoea: Week 66Dyspnoea: Week 69Dyspnoea: Week 72Dyspnoea: Week 75Dyspnoea: Week 78Dyspnoea: Week 81Dyspnoea: Week 84Dyspnoea: Week 87Dyspnoea: Week 90Dyspnoea: Survival Follow-Up Week 12Dyspnoea: Survival Follow-Up Week 24
Arm B (Carboplatin or Cisplatin + Pemetrexed)-1.95-1.230.20-0.91-1.67-2.12-5.67-2.75-2.53-1.25-1.83-3.83-1.67-3.27-6.25-5.13-14.81-9.68-7.69-11.11-7.69-9.52-16.67-4.17-6.670.000.000.000.000.009.205.26

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms as Assessed by European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire-Core 30 (QLQ-C30) Symptom Score

EORTC QLQ-C30 is a validated and reliable self-report measure that consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). EORTC QLQ-C30 is scored according to the EORTC scoring manual (Fayers et al. 2001). All EORTC scales and single-item measures are linearly transformed so that each score has a range of 0-100. A high score for a functional/global health status scale represents a high or healthy level of functioning/HRQoL (Health-Related Quality of Life); however a high score for a symptom scale or item represents a high level of symptomatology or problems. A ≥10-point change in the symptoms subscale score is perceived by patients as clinically significant (Osoba et al. 1998). (NCT02657434)
Timeframe: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)

InterventionUnits on a scale (Mean)
Dyspnoea: Week 3Dyspnoea: Week 6Dyspnoea: Week 9Dyspnoea: Week 12Dyspnoea: Week 15Dyspnoea: Week 18Dyspnoea: Week 21Dyspnoea: Week 24Dyspnoea: Week 27Dyspnoea: Week 30Dyspnoea: Week 33Dyspnoea: Week 36Dyspnoea: Week 39Dyspnoea: Week 42Dyspnoea: Week 45Dyspnoea: Week 48Dyspnoea: Week 51Dyspnoea: Week 54Dyspnoea: Week 57Dyspnoea: Week 60Dyspnoea: Week 63Dyspnoea: Week 66Dyspnoea: Week 69Dyspnoea: Week 72Dyspnoea: Week 75Dyspnoea: Week 78Dyspnoea: Week 81Dyspnoea: Week 84Dyspnoea: Week 87Dyspnoea: Week 90Dyspnoea: Week 93Dyspnoea: Survival Follow-Up Week 12Dyspnoea: Survival Follow-Up Week 24
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed-1.39-4.71-6.33-3.39-2.44-3.44-2.89-2.45-1.32-2.71-3.74-6.67-8.42-9.12-2.11-7.41-2.92-2.78-5.630.00-5.13-1.80-3.570.00-5.80-4.76-11.11-4.178.330.000.008.00-14.29

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of≥0.5 points for chest pain score is considered to be clinically significant. (NCT02657434)
Timeframe: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)

InterventionUnits on a scale (Mean)
Chest Pain: Week 1Chest Pain: Week 2Chest Pain: Week 3Chest Pain: Week 4Chest Pain: Week 5Chest Pain: Week 6Chest Pain: Week 7Chest Pain: Week 8Chest Pain: Week 9Chest Pain: Week 10Chest Pain: Week 11Chest Pain: Week 12Chest Pain: Week 13Chest Pain: Week 14Chest Pain: Week 15Chest Pain: Week 16Chest Pain: Week 17Chest Pain: Week 18Chest Pain: Week 19Chest Pain: Week 20Chest Pain: Week 21Chest Pain: Week 22Chest Pain: Week 23Chest Pain: Week 24Chest Pain: Week 25Chest Pain: Week 26Chest Pain: Week 27Chest Pain: Week 28Chest Pain: Week 29Chest Pain: Week 30Chest Pain: Week 31Chest Pain: Week 32Chest Pain: Week 33Chest Pain: Week 34Chest Pain: Week 35Chest Pain: Week 36Chest Pain: Week 37Chest Pain: Week 38Chest Pain: Week 39Chest Pain: Week 40Chest Pain: Week 41Chest Pain: Week 42Chest Pain: Week 43Chest Pain: Week 44Chest Pain: Week 45Chest Pain: Week 46Chest Pain: Week 47Chest Pain: Week 48Chest Pain: Week 49Chest Pain: Week 50Chest Pain: Week 51Chest Pain: Week 52Chest Pain: Week 53Chest Pain: Week 54Chest Pain: Week 55Chest Pain: Week 56Chest Pain: Week 57Chest Pain: Week 58Chest Pain: Week 59Chest Pain: Week 60Chest Pain: Week 61Chest Pain: Week 62Chest Pain: Week 63Chest Pain: Week 64Chest Pain: Week 65Chest Pain: Week 66Chest Pain: Week 67Chest Pain: Week 68Chest Pain: Week 69Chest Pain: Week 70Chest Pain: Week 71Chest Pain: Week 72Chest Pain: Week 73Chest Pain: Week 74Chest Pain: Week 75Chest Pain: Week 76Chest Pain: Week 77Chest Pain: Week 78Chest Pain: Week 79Chest Pain: Week 80Chest Pain: Week 81Chest Pain: Week 82Chest Pain: Week 83Chest Pain: Week 84Chest Pain: Week 85Chest Pain: Week 86Chest Pain: Week 87Chest Pain: Week 88Chest Pain: Week 89Chest Pain: Week 90Chest Pain: Week 91Chest Pain: Time of First PdChest Pain: Time of Last Tx DoseCough: Week 1Cough: Week 2Cough: Week 3Cough: Week 4Cough: Week 5Cough: Week 6Cough: Week 7Cough: Week 8Cough: Week 9Cough: Week 10Cough: Week 11Cough: Week 12Cough: Week 13Cough: Week 14Cough: Week 15Cough: Week 16Cough: Week 17Cough: Week 18Cough: Week 19Cough: Week 20Cough: Week 21Cough: Week 22Cough: Week 23Cough: Week 24Cough: Week 25Cough: Week 26Cough: Week 27Cough: Week 28Cough: Week 29Cough: Week 30Cough: Week 31Cough: Week 32Cough: Week 33Cough: Week 34Cough: Week 35Cough: Week 36Cough: Week 37Cough: Week 38Cough: Week 39Cough: Week 40Cough: Week 41Cough: Week 42Cough: Week 43Cough: Week 44Cough: Week 45Cough: Week 46Cough: Week 47Cough: Week 48Cough: Week 49Cough: Week 50Cough: Week 51Cough: Week 52Cough: Week 53Cough: Week 54Cough: Week 55Cough: Week 56Cough: Week 57Cough: Week 58Cough: Week 59Cough: Week 60Cough: Week 61Cough: Week 62Cough: Week 63Cough: Week 64Cough: Week 65Cough: Week 66Cough: Week 67Cough: Week 68Cough: Week 69Cough: Week 70Cough: Week 71Cough: Week 72Cough: Week 73Cough: Week 74Cough: Week 75Cough: Week 76Cough: Week 77Cough: Week 78Cough: Week 79Cough: Week 80Cough: Week 81Cough: Week 82Cough: Week 83Cough: Week 84Cough: Week 85Cough: Week 86Cough: Week 87Cough: Week 88Cough: Week 89Cough: Week 90Cough: Week 91Cough: Time of First PdCough: Time of Last Tx DoseDyspnoea: Week 1Dyspnoea: Week 2Dyspnoea: Week 3Dyspnoea: Week 4Dyspnoea: Week 5Dyspnoea: Week 6Dyspnoea: Week 7Dyspnoea: Week 8Dyspnoea: Week 9Dyspnoea: Week 10Dyspnoea: Week 11Dyspnoea: Week 12Dyspnoea: Week 13Dyspnoea: Week 14Dyspnoea: Week 15Dyspnoea: Week 16Dyspnoea: Week 17Dyspnoea: Week 18Dyspnoea: Week 19Dyspnoea: Week 20Dyspnoea: Week 21Dyspnoea: Week 22Dyspnoea: Week 23Dyspnoea: Week 24Dyspnoea: Week 25Dyspnoea: Week 26Dyspnoea: Week 27Dyspnoea: Week 28Dyspnoea: Week 29Dyspnoea: Week 30Dyspnoea: Week 31Dyspnoea: Week 32Dyspnoea: Week 33Dyspnoea: Week 34Dyspnoea: Week 35Dyspnoea: Week 36Dyspnoea: Week 37Dyspnoea: Week 38Dyspnoea: Week 39Dyspnoea: Week 40Dyspnoea: Week 41Dyspnoea: Week 42Dyspnoea: Week 43Dyspnoea: Week 44Dyspnoea: Week 45Dyspnoea: Week 46Dyspnoea: Week 47Dyspnoea: Week 48Dyspnoea: Week 49Dyspnoea: Week 50Dyspnoea: Week 51Dyspnoea: Week 52Dyspnoea: Week 53Dyspnoea: Week 54Dyspnoea: Week 55Dyspnoea: Week 56Dyspnoea: Week 57Dyspnoea: Week 58Dyspnoea: Week 59Dyspnoea: Week 60Dyspnoea: Week 61Dyspnoea: Week 62Dyspnoea: Week 63Dyspnoea: Week 64Dyspnoea: Week 65Dyspnoea: Week 66Dyspnoea: Week 67Dyspnoea: Week 68Dyspnoea: Week 69Dyspnoea: Week 70Dyspnoea: Week 71Dyspnoea: Week 72Dyspnoea: Week 73Dyspnoea: Week 74Dyspnoea: Week 75Dyspnoea: Week 76Dyspnoea: Week 77Dyspnoea: Week 78Dyspnoea: Week 79Dyspnoea: Week 80Dyspnoea: Week 81Dyspnoea: Week 82Dyspnoea: Week 83Dyspnoea: Week 84Dyspnoea: Week 85Dyspnoea: Week 86Dyspnoea: Week 87Dyspnoea: Week 88Dyspnoea: Week 89Dyspnoea: Week 90Dyspnoea: Week 91Dyspnoea: Time of First PdDyspnoea: Time of Last Tx Dose
Arm B (Carboplatin or Cisplatin + Pemetrexed)0.20-0.01-0.050.03-0.02-0.050.070.030.060.030.02-0.02-0.05-0.070.130.020.02-0.06-0.15-0.020.030.04-0.08-0.020.05-0.050.040.240.060.010.020.210.040.210.330.150.150.120.200.15-0.05-0.06-0.22-0.10-0.20-0.060.020.02-0.09-0.13-0.020.140.130.110.120.130.120.270.230.140.230.460.250.150.110.420.360.330.070.250.30-0.130.130.380.380.00-0.25-0.750.00-0.25-0.25-0.75-0.250.00-1.000.00-1.00-1.00-1.000.000.000.280.17-0.08-0.13-0.05-0.11-0.14-0.16-0.22-0.20-0.17-0.22-0.21-0.13-0.24-0.23-0.11-0.20-0.20-0.19-0.25-0.25-0.19-0.29-0.34-0.27-0.24-0.25-0.19-0.19-0.25-0.08-0.130.010.05-0.10-0.270.01-0.110.020.02-0.10-0.27-0.31-0.200.00-0.18-0.25-0.43-0.26-0.50-0.37-0.45-0.29-0.24-0.27-0.10-0.30-0.41-0.17-0.31-0.55-0.230.04-0.29-0.45-0.61-0.17-0.64-0.75-0.57-0.83-0.90-1.25-0.63-0.63-0.63-1.00-0.50-1.00-0.25-0.50-0.50-0.50-1.00-0.500.000.000.000.000.000.000.00-0.08-0.150.200.110.100.210.220.230.300.350.340.460.390.380.340.440.450.370.350.350.300.300.220.160.240.300.500.300.430.460.430.450.350.480.360.470.420.590.530.590.650.620.630.500.320.580.490.550.530.550.630.520.670.720.810.820.770.840.680.770.660.730.850.950.670.460.400.670.370.470.430.330.40-0.050.450.500.55-0.070.000.000.000.100.100.000.000.000.200.000.200.200.200.200.000.580.47

[back to top]

Change From Baseline in Patient-Reported Lung Cancer Symptoms as Reported Using the Symptoms in Lung Cancer (SILC) Scale Score

Change from baseline per SILC scale will be analyzed for each lung cancer symptoms scores. SILC questionnaire comprises 3 individual symptoms & are scored at individual symptom level, thus have a dyspnea score, chest pain score, & cough score. There are a total of 9 questions in SILC questionnaire, each question has a minimum value of 0 & maximum value of 4. Each individual symptom score is calculated as average of responses for symptom items. 'Chest pain' score is mean of question 1 & 2, 'Cough' score is mean of question 3 & 4 and 'Dyspnea' score is mean of question 5 to 9 in SILC questionnaire. An increase in score is suggestive of a worsening in symptomology. A score change of ≥0.3 points for dyspnea & cough symptom scores is considered to be clinically significant; whereas a score change of≥0.5 points for chest pain score is considered to be clinically significant. (NCT02657434)
Timeframe: Baseline up to 3 and 6 months after disease progression or loss of clinical benefit (up to approximately 25 months)

InterventionUnits on a scale (Mean)
Chest Pain: Week 1Chest Pain: Week 2Chest Pain: Week 3Chest Pain: Week 4Chest Pain: Week 5Chest Pain: Week 6Chest Pain: Week 7Chest Pain: Week 8Chest Pain: Week 9Chest Pain: Week 10Chest Pain: Week 11Chest Pain: Week 12Chest Pain: Week 13Chest Pain: Week 14Chest Pain: Week 15Chest Pain: Week 16Chest Pain: Week 17Chest Pain: Week 18Chest Pain: Week 19Chest Pain: Week 20Chest Pain: Week 21Chest Pain: Week 22Chest Pain: Week 23Chest Pain: Week 24Chest Pain: Week 25Chest Pain: Week 26Chest Pain: Week 27Chest Pain: Week 28Chest Pain: Week 29Chest Pain: Week 30Chest Pain: Week 31Chest Pain: Week 32Chest Pain: Week 33Chest Pain: Week 34Chest Pain: Week 35Chest Pain: Week 36Chest Pain: Week 37Chest Pain: Week 38Chest Pain: Week 39Chest Pain: Week 40Chest Pain: Week 41Chest Pain: Week 42Chest Pain: Week 43Chest Pain: Week 44Chest Pain: Week 45Chest Pain: Week 46Chest Pain: Week 47Chest Pain: Week 48Chest Pain: Week 49Chest Pain: Week 50Chest Pain: Week 51Chest Pain: Week 52Chest Pain: Week 53Chest Pain: Week 54Chest Pain: Week 55Chest Pain: Week 56Chest Pain: Week 57Chest Pain: Week 58Chest Pain: Week 59Chest Pain: Week 60Chest Pain: Week 61Chest Pain: Week 62Chest Pain: Week 63Chest Pain: Week 64Chest Pain: Week 65Chest Pain: Week 66Chest Pain: Week 67Chest Pain: Week 68Chest Pain: Week 69Chest Pain: Week 70Chest Pain: Week 71Chest Pain: Week 72Chest Pain: Week 73Chest Pain: Week 74Chest Pain: Week 75Chest Pain: Week 76Chest Pain: Week 77Chest Pain: Week 78Chest Pain: Week 79Chest Pain: Week 80Chest Pain: Week 81Chest Pain: Week 82Chest Pain: Week 83Chest Pain: Week 84Chest Pain: Week 85Chest Pain: Week 86Chest Pain: Week 87Chest Pain: Week 88Chest Pain: Week 89Chest Pain: Week 90Chest Pain: Week 91Chest Pain: Week 92Chest Pain: Week 93Chest Pain: Week 94Chest Pain: Week 95Chest Pain: Time of First PdChest Pain: Time of Last Tx DoseCough: Week 1Cough: Week 2Cough: Week 3Cough: Week 4Cough: Week 5Cough: Week 6Cough: Week 7Cough: Week 8Cough: Week 9Cough: Week 10Cough: Week 11Cough: Week 12Cough: Week 13Cough: Week 14Cough: Week 15Cough: Week 16Cough: Week 17Cough: Week 18Cough: Week 19Cough: Week 20Cough: Week 21Cough: Week 22Cough: Week 23Cough: Week 24Cough: Week 25Cough: Week 26Cough: Week 27Cough: Week 28Cough: Week 29Cough: Week 30Cough: Week 31Cough: Week 32Cough: Week 33Cough: Week 34Cough: Week 35Cough: Week 36Cough: Week 37Cough: Week 38Cough: Week 39Cough: Week 40Cough: Week 41Cough: Week 42Cough: Week 43Cough: Week 44Cough: Week 45Cough: Week 46Cough: Week 47Cough: Week 48Cough: Week 49Cough: Week 50Cough: Week 51Cough: Week 52Cough: Week 53Cough: Week 54Cough: Week 55Cough: Week 56Cough: Week 57Cough: Week 58Cough: Week 59Cough: Week 60Cough: Week 61Cough: Week 62Cough: Week 63Cough: Week 64Cough: Week 65Cough: Week 66Cough: Week 67Cough: Week 68Cough: Week 69Cough: Week 70Cough: Week 71Cough: Week 72Cough: Week 73Cough: Week 74Cough: Week 75Cough: Week 76Cough: Week 77Cough: Week 78Cough: Week 79Cough: Week 80Cough: Week 81Cough: Week 82Cough: Week 83Cough: Week 84Cough: Week 85Cough: Week 86Cough: Week 87Cough: Week 88Cough: Week 89Cough: Week 90Cough: Week 91Cough: Week 92Cough: Week 93Cough: Week 94Cough: Week 95Cough: Time of First PdCough: Time of Last Tx DoseDyspnoea: Week 1Dyspnoea: Week 2Dyspnoea: Week 3Dyspnoea: Week 4Dyspnoea: Week 5Dyspnoea: Week 6Dyspnoea: Week 7Dyspnoea: Week 8Dyspnoea: Week 9Dyspnoea: Week 10Dyspnoea: Week 11Dyspnoea: Week 12Dyspnoea: Week 13Dyspnoea: Week 14Dyspnoea: Week 15Dyspnoea: Week 16Dyspnoea: Week 17Dyspnoea: Week 18Dyspnoea: Week 19Dyspnoea: Week 20Dyspnoea: Week 21Dyspnoea: Week 22Dyspnoea: Week 23Dyspnoea: Week 24Dyspnoea: Week 25Dyspnoea: Week 26Dyspnoea: Week 27Dyspnoea: Week 28Dyspnoea: Week 29Dyspnoea: Week 30Dyspnoea: Week 31Dyspnoea: Week 32Dyspnoea: Week 33Dyspnoea: Week 34Dyspnoea: Week 35Dyspnoea: Week 36Dyspnoea: Week 37Dyspnoea: Week 38Dyspnoea: Week 39Dyspnoea: Week 40Dyspnoea: Week 41Dyspnoea: Week 42Dyspnoea: Week 43Dyspnoea: Week 44Dyspnoea: Week 45Dyspnoea: Week 46Dyspnoea: Week 47Dyspnoea: Week 48Dyspnoea: Week 49Dyspnoea: Week 50Dyspnoea: Week 51Dyspnoea: Week 52Dyspnoea: Week 53Dyspnoea: Week 54Dyspnoea: Week 55Dyspnoea: Week 56Dyspnoea: Week 57Dyspnoea: Week 58Dyspnoea: Week 59Dyspnoea: Week 60Dyspnoea: Week 61Dyspnoea: Week 62Dyspnoea: Week 63Dyspnoea: Week 64Dyspnoea: Week 65Dyspnoea: Week 66Dyspnoea: Week 67Dyspnoea: Week 68Dyspnoea: Week 69Dyspnoea: Week 70Dyspnoea: Week 71Dyspnoea: Week 72Dyspnoea: Week 73Dyspnoea: Week 74Dyspnoea: Week 75Dyspnoea: Week 76Dyspnoea: Week 77Dyspnoea: Week 78Dyspnoea: Week 79Dyspnoea: Week 80Dyspnoea: Week 81Dyspnoea: Week 82Dyspnoea: Week 83Dyspnoea: Week 84Dyspnoea: Week 85Dyspnoea: Week 86Dyspnoea: Week 87Dyspnoea: Week 88Dyspnoea: Week 89Dyspnoea: Week 90Dyspnoea: Week 91Dyspnoea: Week 92Dyspnoea: Week 93Dyspnoea: Week 94Dyspnoea: Week 95Dyspnoea: Time of First PdDyspnoea: Time of Last Tx Dose
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed0.300.210.060.03-0.01-0.02-0.04-0.07-0.030.020.04-0.010.050.060.080.080.000.120.02-0.010.010.020.040.090.140.090.040.030.040.040.05-0.010.030.110.110.170.060.040.130.040.090.030.130.100.030.080.090.050.030.000.120.00-0.01-0.080.030.04-0.01-0.12-0.23-0.150.00-0.04-0.060.09-0.030.130.020.12-0.050.030.04-0.22-0.10-0.02-0.07-0.06-0.21-0.25-0.18-0.12-0.250.00-0.50-0.30-0.20-0.500.500.000.000.000.000.000.001.000.500.200.13-0.06-0.08-0.07-0.22-0.33-0.33-0.22-0.28-0.29-0.35-0.33-0.40-0.37-0.34-0.33-0.33-0.31-0.31-0.36-0.39-0.36-0.41-0.44-0.29-0.27-0.22-0.32-0.32-0.34-0.34-0.37-0.45-0.44-0.29-0.32-0.31-0.37-0.31-0.33-0.35-0.30-0.31-0.37-0.36-0.41-0.34-0.29-0.38-0.40-0.40-0.15-0.10-0.13-0.16-0.35-0.26-0.25-0.45-0.50-0.52-0.38-0.53-0.57-0.49-0.39-0.43-0.47-0.35-0.53-0.43-0.56-0.72-0.77-0.54-0.67-0.65-0.82-0.57-0.64-1.04-0.79-0.890.13-0.200.00-0.38-0.83-0.880.000.25-0.500.500.500.500.00-0.45-0.290.160.150.120.170.170.160.250.240.170.160.260.220.300.220.190.260.150.220.220.270.220.280.220.240.280.240.240.250.200.210.150.160.170.240.230.220.240.220.190.190.160.170.220.230.210.230.140.140.160.240.300.270.220.230.160.180.110.160.070.270.230.160.270.140.120.160.260.250.160.070.130.060.090.270.450.020.090.030.19-0.26-0.170.180.450.600.32-0.15-0.47-0.70-0.20-0.50-0.50-0.70-0.40-0.80-1.000.400.18

[back to top]

Minimum Observed Serum Atezolizumab Concentration (Cmin)

Minimum observed serum atezolizumab concentration (Cmin) prior to infusion at selected cycles (Arm A) (NCT02657434)
Timeframe: Predose (Prd; 0 hour [h]) on D1 of Cy 2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle (up to approximately 25 months)

Interventionμg/mL (Mean)
Cy2D1Cy3D1Cy4D1Cy8D1Cy16D1Cy24D1Treatment Discontinuation VisitDay 120 Post Last Dose
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed69.811515122123425712913.4

[back to top]

Percentage of Participants With an Objective Response (Complete Response [CR] or Partial Response [PR]) Assessed by the Investigator Using RECIST V1.1

An objective response is defined as either an unconfirmed CR or a PR, as determined by the investigator using RECIST v1.1. Objective Response Rate is defined as the proportion of patients who had an objective response. (NCT02657434)
Timeframe: Randomization up to approximately 25 months

,
InterventionPercentage of Participants (Number)
RespondersNon-Responders
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed51.748.3
Arm B (Carboplatin or Cisplatin + Pemetrexed)37.462.6

[back to top]

Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) of Atezolizumab

Baseline prevalence and post-baseline incidence of anti-drug antibodies (ADA) to Atezolizumab in the Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed) (NCT02657434)
Timeframe: Prd (0 h) on D1 of Cy1,2,3,4,8,16 (Cy length=21 days) and thereafter on D1 of every 8th cycle, at treatment discontinuation & then every 30 days (up to 120 days) after last dose of atezolizumab (up to app 25 months)

InterventionPercentage of Participants (Number)
Baseline Evaluable ParticipantsPost-Baseline Evaluable Participants
Arm A (Atezolizumab + Carboplatin or Cisplatin + Pemetrexed1.835.4

[back to top]

Number of Participants With Dose Limiting Toxicities (DLTs) - Part 2

"Dose limiting toxicities (DLTs) were defined as any of the items listed below.~Any Grade 2 drug-related uveitis or eye pain that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment.~Any Grade 2 drug-related pneumonitis or interstitial lung disease that does not resolve to dose delay and systemic steroids in 14 days.~Any Grade 3 non-skin drug-related adverse event with the exception of laboratory abnormalities that cannot be alleviated or controlled by appropriate care within 14 days.~Any Grade 4 drug-related adverse event including laboratory abnormalities except Grade 4 leukopenia or neutropenia lasting < 14 days and asymptomatic amylase/lipase elevation.~Drug-related hepatic function laboratory abnormalities." (NCT02659059)
Timeframe: 9 weeks after first dose

InterventionParticipants (Count of Participants)
Nivolumab+Ipilimumab+Chemotherapy1

[back to top]

Progression Free Survival (PFS) by Tumor Mutation Burden (TMB) Levels - Part 1

"Progression Free Survival (PFS) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.~High TMB = ≥ 10 mutations per megabase Low TMB = < 10 mutations per megabase" (NCT02659059)
Timeframe: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)

InterventionMonths (Median)
High TMB (>=10 Mutations/MB)Low TMB (<10 Mutations/MB)
Nivolumab+Ipilimumab10.842.79

[back to top]

Overall Survival (OS) - Part 1

Overall survival (OS) was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive. (NCT02659059)
Timeframe: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

InterventionMonths (Median)
Nivolumab+Ipilimumab20.83

[back to top]

Overall Survival (OS) by Tumor Mutation Burden (TMB) Levels - Part 1

"Overall survival (OS) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.~High TMB = ≥ 10 mutations per megabase Low TMB = < 10 mutations per megabase" (NCT02659059)
Timeframe: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

InterventionMonths (Median)
High TMB (>=10 Mutations/MB)Low TMB (<10 Mutations/MB)
Nivolumab+Ipilimumab47.3111.33

[back to top]

Number of Participants With Adverse Events (AEs) - Part 2

Number of participants with adverse events (AEs) including serious adverse events (SAEs) and deaths graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy. (NCT02659059)
Timeframe: Deaths are from first dose to database lock (Up to 24 months). AEs and SAEs are from first dose to 30 days post last dose

InterventionParticipants (Count of Participants)
Adverse Events (AEs)Serious Adverse Events (SAEs)Deaths due to Disease progressionDeaths due to Study drug toxicityDeaths due to unknown causesDeaths due to other causes
Nivolumab+Ipilimumab+Chemotherapy36269016

[back to top]

Objective Response Rate (ORR) by PD-L1 Positive and Negative Levels - Part 1

Objective response rate (ORR) in PD-L1 positive (PD-L1 ≥1%) and PD-L1 negative (PD-L1 <1%) participants was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment. (NCT02659059)
Timeframe: From first dose to database lock (Up to 18 months)

InterventionPercentage of participants (Number)
PD-L1 ≥1%PD-L1 <1%
Nivolumab+Ipilimumab41.314.9

[back to top]

Objective Response Rate (ORR) by PD-L1 Expression Levels-Part 1

"Objective response rate (ORR) by PD-L1 expression levels was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.~CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 <1% = PD-L1 negative (membranous staining in <1% tumor cells)" (NCT02659059)
Timeframe: From first dose up to approximately 72 months

InterventionPercentage of participants (Number)
PD-L1 ≥1%PD-L1 <1%
Nivolumab+Ipilimumab44.217.1

[back to top]

Number of Participants With Laboratory Abnormalities in Thyroid Tests - Part 2

Number of participants with specific thyroid laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy. (NCT02659059)
Timeframe: From first dose to 30 days post last dose

InterventionParticipants (Count of Participants)
TSH > ULNTSH > ULN with TSH <= ULN at baselineTSH > ULN with at least one FT3/FT4 test value < LLNTSH > ULN with all other FT3/FT4 test values ≥ LLNTSH > ULN with FT3/FT4 test missingTSH < LLNTSH < LLN with TSH >= LLN at baselineTSH < LLN with at least one FT3/FT4 test value > ULNTSH < LLN with all other FT3/FT4 test values <= ULNTSH < LLN with FT3/Ft4 test missing
Nivolumab+Ipilimumab+Chemotherapy1078111312760

[back to top]

Number of Participants With Laboratory Abnormalities in Hepatic Tests - Part 2

Number of participant with specific liver laboratory abnormalities graded by Common Terminology Criteria for Adverse Events (CTCAE v4.0) to determine the safety and tolerability of Nivolumab and Ipilimumab combined with chemotherapy. (NCT02659059)
Timeframe: From first dose to 30 days post last dose

InterventionParticipants (Count of Participants)
ALT OR AST >3XULNALT OR AST >5XULNALT OR AST >10XULNALT OR AST >20XULNTOTAL BILIRUBIN >2XULNConcurrent ALT OR AST >3XULN & BILIRUBIN >2XULN within 1 dayConcurrent ALT OR AST >3XULN & BILIRUBIN >2XULN within 30 days
Nivolumab+Ipilimumab+Chemotherapy2211000

[back to top]

Progression Free Survival (PFS) - Part 2

Progression Free Survival (PFS) was defined as the time between the date of first dose and the first date of documented progression, as determined by investigator (per RECIST 1.1), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT02659059)
Timeframe: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 59 months)

InterventionMonths (Median)
Nivolumab+Ipilimumab+Chemotherapy10.81

[back to top]

Overall Survival (OS) by PD-L1 Expression Levels - Part 1

"Overall survival (OS) by PD-L1 expression levels was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive.~PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 <1% = PD-L1 negative (membranous staining in <1% tumor cells)" (NCT02659059)
Timeframe: From the date of first treatment to the date of death due to any cause (Up to approximately 72 months)

InterventionMonths (Median)
PD-L1 ≥1%PD-L1 <1%
Nivolumab+Ipilimumab26.5113.70

[back to top]

Objective Response Rate (ORR) by Tumor Mutation Burden (TMB) Levels - Part 1

"Objective response rate (ORR) by tumor mutational burden (TMB) using DNA derived from tumor specimens was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.~CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~High TMB = ≥ 10 mutations per megabase Low TMB = < 10 mutations per megabase" (NCT02659059)
Timeframe: From first dose up to approximately 72 months

InterventionPercentage of participants (Number)
High TMB (>=10 Mutations/MB)Low TMB (<10 Mutations/MB)
Nivolumab+Ipilimumab52.116.0

[back to top]

Progression Free Survival (PFS) - Part 1

Progression Free Survival (PFS) was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT02659059)
Timeframe: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)

InterventionMonths (Median)
Nivolumab+Ipilimumab5.19

[back to top]

Overall Survival (OS) - Part 2

Overall survival (OS) was defined as the time from date of first treatment to the date of death due to any cause. A participant who has not died will be censored at the last known date alive. (NCT02659059)
Timeframe: From the date of first treatment to the date of death due to any cause (Up to approximately 59 months)

InterventionMonths (Median)
Nivolumab+Ipilimumab+Chemotherapy19.35

[back to top]

Progression Free Survival (PFS) by PD-L1 Expression Levels - Part 1

"Progression Free Survival (PFS) by PD-L1 expression levels was defined as the time between the date of first dose and the first date of documented progression, as determined by blinded independent central review (BICR), or death due to any cause, whichever occurred first. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.~PD-L1 ≥1% = PD-L1 positive (membranous staining in ≥ 1% tumor cells) PD-L1 <1% = PD-L1 negative (membranous staining in <1% tumor cells)" (NCT02659059)
Timeframe: From first dose to the first date of documented progression, or death due to any cause, whichever occurred first (Up to approximately 72 months)

InterventionMonths (Median)
PD-L1 ≥1%PD-L1 <1%
Nivolumab+Ipilimumab6.802.92

[back to top]

Objective Response Rate (ORR) - Part 1

"Objective response rate (ORR) was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on Blinded Independent Central Review (BICR) assessment.~CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters." (NCT02659059)
Timeframe: From first dose up to approximately 72 months

InterventionPercentage of participants (Number)
Nivolumab+Ipilimumab32.3

[back to top]

Objective Response Rate (ORR) - Part 2

"Objective response rate (ORR) was defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on investigator assessment.~CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters." (NCT02659059)
Timeframe: From first dose up to approximately 59 months

InterventionPercentage of participants (Number)
Nivolumab+Ipilimumab+Chemotherapy47.2

[back to top]

HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456173Week 172456174Week 572456174Week 572456173
Very good, good, and neither good nor badUnable to answer questionMissingBadVery bad
HGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib15
LGG Cohort: Dabrafenib and Trametinib5
HGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib4
LGG Cohort: Dabrafenib and Trametinib9
HGG Cohort: Dabrafenib and Trametinib5
LGG Cohort: Dabrafenib and Trametinib12
LGG Cohort: Dabrafenib and Trametinib6
LGG Cohort: Dabrafenib and Trametinib2
HGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib1
HGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib14

[back to top]

LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score

"The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 7 items measuring the global health of the patient. 4 items used a 5-level Likert scale with 1=poor and 5=excellent; 1 item used a 5-level Likert scale with 1=never and 5=always; and 2 items used a 5-level Likert scale with 1=never and 5=almost always. The total raw global health score, ranging from 7 to 35, was computed by summing item values, with higher scores indicating better overall well-being. Raw scores were then transformed into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores reflected better global health status.~Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up." (NCT02684058)
Timeframe: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)

InterventionScore on a Scale (Mean)
BaselineWeek 5 Day 1Week 8 Day 1Week 16 Day 1Week 24 Day 1Week 32 Day 1Week 40 Day 1Week 48 Day 1Week 56 Day 1Week 72 Day 1Week 88 Day 1Week 104 Day 1Week 120 Day 1Week 136 Day 1Week 152 Day 1Week 168 Day 1EOTPost Treatment Follow-Up 1Post Treatment Follow-Up 2Post Treatment Follow-Up 3Post Treatment Follow-Up 4Post Treatment Follow-Up 5
LGG Cohort: Dabrafenib and Trametinib42.6742.1443.8344.6845.2745.4645.3744.8344.5444.2144.9145.6044.4144.4547.8846.4844.9845.4027.7043.6031.2029.40

[back to top]

LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score

"The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the pain of the participants. Pain item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening pain. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated more severe pain experiences.~Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up." (NCT02684058)
Timeframe: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)

InterventionScore on a Scale (Mean)
BaselineWeek 5 Day 1Week 8 Day 1Week 16 Day 1Week 24 Day 1Week 32 Day 1Week 40 Day 1Week 48 Day 1Week 56 Day 1EOTPost Treatment Follow-Up 1Post Treatment Follow-Up 2Post Treatment Follow-Up 3Post Treatment Follow-Up 4Post Treatment Follow-Up 5Post Treatment Follow-Up 6Post Treatment Follow-Up 8
LGG Cohort: Carboplatin and Vincristine52.6450.9751.0051.7551.8149.5952.5251.2053.9952.8750.6043.2543.2543.2543.2550.8843.25

[back to top]

LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Pain Score

"The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the pain of the participants. Pain item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening pain. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated more severe pain experiences.~Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up." (NCT02684058)
Timeframe: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)

InterventionScore on a Scale (Mean)
BaselineWeek 5 Day 1Week 8 Day 1Week 16 Day 1Week 24 Day 1Week 32 Day 1Week 40 Day 1Week 48 Day 1Week 56 Day 1Week 72 Day 1Week 88 Day 1Week 104 Day 1Week 120 Day 1Week 136 Day 1Week 152 Day 1Week 168 Day 1EOTPost Treatment Follow-Up 1Post Treatment Follow-Up 2Post Treatment Follow-Up 3Post Treatment Follow-Up 4Post Treatment Follow-Up 5
LGG Cohort: Dabrafenib and Trametinib52.1450.1149.9349.7250.6548.7749.8749.8948.1449.4647.8248.7448.5646.1647.4248.6151.4653.0558.5153.0558.5158.51

[back to top]

T1/2 for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)

PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

,
Interventionhr (Geometric Mean)
DabrafenibCarboxy-dabrafenibDesmethyl-dabrafenibHydroxy-dabrafenib
HGG Cohort: Dabrafenib and Trametinib2.487.127.062.66
LGG Cohort: Dabrafenib and Trametinib3.096.5916.13.52

[back to top]

Tmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)

PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

,
Interventionhr (Geometric Mean)
DabrafenibCarboxy-dabrafenibDesmethyl-dabrafenibHydroxy-dabrafenib
HGG Cohort: Dabrafenib and Trametinib1.473.372.211.97
LGG Cohort: Dabrafenib and Trametinib1.473.662.291.68

[back to top]

HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456173Week 172456174Week 572456174Week 572456173
BadVery badUnable to answer questionVery good, good, and neither good nor badMissing
HGG Cohort: Dabrafenib and Trametinib4
LGG Cohort: Dabrafenib and Trametinib13
HGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib6
LGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib10
HGG Cohort: Dabrafenib and Trametinib5
LGG Cohort: Dabrafenib and Trametinib16
LGG Cohort: Dabrafenib and Trametinib2
HGG Cohort: Dabrafenib and Trametinib0
HGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib11

[back to top]

AUClast for Trametinib

Pharmacokinetic (PK) parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast). (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Interventionhour (hr) * nanogram (ng)/mililiter (mL) (Geometric Mean)
HGG Cohort: Dabrafenib and Trametinib282
LGG Cohort: Dabrafenib and Trametinib328

[back to top]

AUCtau for Trametinib

PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Interventionhr * ng/mL (Geometric Mean)
HGG Cohort: Dabrafenib and Trametinib307
LGG Cohort: Dabrafenib and Trametinib339

[back to top]

Cmax for Trametinib

PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Interventionng/mL (Geometric Mean)
HGG Cohort: Dabrafenib and Trametinib21.3
LGG Cohort: Dabrafenib and Trametinib22.7

[back to top]

Ctrough for Trametinib

PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose

Interventionng/ml (Geometric Mean)
HGG Cohort: Dabrafenib and Trametinib8.73
LGG Cohort: Dabrafenib and Trametinib9.82

[back to top]

HGG Cohort: Clinical Benefit Rate (CBR) as Per Central Independent Assessment Using RANO Criteria

"Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.~SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status." (NCT02684058)
Timeframe: Up to approx. 4.8 years

InterventionPercentage of participants (Number)
HGG Cohort: Dabrafenib and Trametinib65.9

[back to top]

HGG Cohort: Clinical Benefit Rate (CBR) as Per Investigator Assessment Using RANO Criteria

"Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.~SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status." (NCT02684058)
Timeframe: Up to approx. 4.8 years

InterventionPercentage of participants (Number)
HGG Cohort: Dabrafenib and Trametinib75.6

[back to top]

HGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)

Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact. (NCT02684058)
Timeframe: Up to 5.1 years

InterventionMonths (Median)
HGG Cohort: Dabrafenib and TrametinibNA

[back to top]

HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria

Time from the date of first dose of study treatment to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. (NCT02684058)
Timeframe: Up to approx. 4.8 years

InterventionMonths (Median)
HGG Cohort: Dabrafenib and Trametinib9.0

[back to top]

HGG Cohort: Kaplan-Meier Estimates of Progression Free Survival (PFS) as Per Investigatort Assessment Using RANO Criteria

Time from the date of first dose of study treatment to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. (NCT02684058)
Timeframe: Up to approx. 4.8 years

InterventionMonths (Median)
HGG Cohort: Dabrafenib and Trametinib24.0

[back to top]

HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria

"Percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 3.2 years

InterventionPercentage of participants (Number)
HGG Cohort: Dabrafenib and Trametinib56.1

[back to top]

HGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)

Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time (NCT02684058)
Timeframe: Up to approx 4.8 years

InterventionPercentage of participants (Number)
HGG Cohort: Dabrafenib and Trametinib56.1

[back to top]

HGG Cohort: Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria

"Time from start of treatment to first documented response of CR or PR as per independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 4.8 years

InterventionMonths (Median)
HGG Cohort: Dabrafenib and Trametinib8.5

[back to top]

HGG Cohort: Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria

"Time from start of treatment to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 4.8 years

InterventionMonths (Median)
HGG Cohort: Dabrafenib and Trametinib3.4

[back to top]

LGG Cohort: 2-year OS Estimate

OS was defined as the time from the first dose to death due to any cause in the LGG cohort. The 2-year Kaplan-Meier OS estimate represented the estimated percentage of participants remaining free from OS events for up to 2 years. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact (NCT02684058)
Timeframe: 2 years from first dose

InterventionPercentage of participants (Number)
LGG Cohort: Dabrafenib and Trametinib100.0
LGG Cohort: Carboplatin and Vincristine96.9

[back to top]

LGG Cohort: Clinical Benefit Rate (CBR) by Central Independent Assessment Using RANO Criteria

"Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.~SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status." (NCT02684058)
Timeframe: Up to approx. 4.2 years

InterventionPercentage of participants (Number)
LGG Cohort: Dabrafenib and Trametinib86.3
LGG Cohort: Carboplatin and Vincristine43.2

[back to top]

LGG Cohort: Clinical Benefit Rate (CBR) by Investigator Assessment Using RANO Criteria

"Percentage of participants with a best overall response of CR or PR, or stable disease (SD) which lasts for 24 weeks or longer.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically.~SD: Partient did not qualify for CR, PR, or progressive disease and has stable nonenhancing (T2/FLAIR) lesions on same or lower doses of corticosteroids compared with baseline scan and clinically stable status." (NCT02684058)
Timeframe: Up to approx. 4.2 years

InterventionPercentage of participants (Number)
LGG Cohort: Dabrafenib and Trametinib91.8
LGG Cohort: Carboplatin and Vincristine56.8

[back to top]

LGG Cohort: Kaplan-Meier Estimates of Overall Survival (OS)

Time from first dose to death due to any cause in the LGG cohort. Confidence Intervals were estimated using the Brookmeyer Crowley method. If a patient was not known to have died at the time of analysis cut-off, OS was censored at the date of last contact. (NCT02684058)
Timeframe: Up to 4.6 years

InterventionMonths (Median)
LGG Cohort: Dabrafenib and TrametinibNA
LGG Cohort: Carboplatin and VincristineNA

[back to top]

LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Central Independent Assessment Using RANO Criteria

"Time from randomization to first documented response of CR or PR as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically (NCT02684058)
Timeframe: Up to approx. 4.2 years

InterventionMonths (Median)
LGG Cohort: Dabrafenib and Trametinib11.0
LGG Cohort: Carboplatin and VincristineNA

[back to top]

LGG Cohort: Kaplan-Meier Estimates of Time to Response (TTR) as Per Investigator Assessment Using RANO Criteria

"Time from randomization to first documented response of CR or PR as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients without an event were censored either at the maximum follow-up time (if they experienced disease progression or death), or at their last tumor assessment date.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 4.2 years

InterventionMonths (Median)
LGG Cohort: Dabrafenib and Trametinib7.4
LGG Cohort: Carboplatin and VincristineNA

[back to top]

LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using RANO Criteria (Longer Follow-up Time)

Percentage of participants with a best overall confirmed CR or PR as assessed per RANO criteria by central independent assessment. The 95% CIs were computed using two-sided exact binomial method. CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses. PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically. This analysis was conducted at the end of the trial (after the primary endpoint analysis cut-off date) and includes a longer follow-up time (NCT02684058)
Timeframe: Up to approx 4.2 years

InterventionPercentage of participants (Number)
LGG Cohort: Dabrafenib and Trametinib54.8
LGG Cohort: Carboplatin and Vincristine16.2

[back to top]

HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Immediate Reaction Once the Medication Was Placed Into the Mouth

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456173Week 172456174Week 572456173Week 572456174
Very good, good, and neither good nor badBadVery badUnable to answer questionMissing
HGG Cohort: Dabrafenib and Trametinib4
LGG Cohort: Dabrafenib and Trametinib13
HGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib5
HGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib3
HGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib10
HGG Cohort: Dabrafenib and Trametinib5
LGG Cohort: Dabrafenib and Trametinib18
LGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib11

[back to top]

HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Remaining After-taste Once Rinsing the Mouth With Water

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456173Week 172456174Week 572456173Week 572456174
Very badUnable to answer questionMissingVery good, good, and neither good nor badBad
HGG Cohort: Dabrafenib and Trametinib4
LGG Cohort: Dabrafenib and Trametinib15
HGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib0
HGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib7
LGG Cohort: Dabrafenib and Trametinib5
HGG Cohort: Dabrafenib and Trametinib6
LGG Cohort: Dabrafenib and Trametinib17
LGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib4
HGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib8

[back to top]

HGG and LGG Cohort: Palatability of Dabrafenib Oral Suspension Based on the Palatability Questionnaire Item: Taste of the Medication Before Rinsing the Mouth

Participants who received the dabrafenib dispersible tablets for oral suspension completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on how it tasted before rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456173Week 172456174Week 572456174Week 572456173
Very good, good, and neither good nor badBadVery badUnable to answer questionMissing
HGG Cohort: Dabrafenib and Trametinib5
LGG Cohort: Dabrafenib and Trametinib18
LGG Cohort: Dabrafenib and Trametinib4
HGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib5
HGG Cohort: Dabrafenib and Trametinib1
HGG Cohort: Dabrafenib and Trametinib6
LGG Cohort: Dabrafenib and Trametinib20
LGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib2
HGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib8

[back to top]

HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: After- Taste Once the Medication Was Swallowed

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after the medication was swallowed, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456173Week 172456174Week 572456174Week 572456173
Unable to answer questionMissingVery good, good, and neither good nor badBadVery bad
HGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib15
LGG Cohort: Dabrafenib and Trametinib5
HGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib11
HGG Cohort: Dabrafenib and Trametinib5
LGG Cohort: Dabrafenib and Trametinib16
LGG Cohort: Dabrafenib and Trametinib3
HGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib13

[back to top]

HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Immediate Reaction Once the Medication Was Placed Into the Mouth

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the immediate reaction once the medication was placed into their mouth, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456174Week 172456173Week 572456173Week 572456174
BadVery BadUnable to answer questionMissingVery good, good, and neither good nor bad
LGG Cohort: Dabrafenib and Trametinib15
HGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib4
HGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib2
HGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib11
HGG Cohort: Dabrafenib and Trametinib5
LGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib13

[back to top]

HGG and LGG Cohort: Palatability of Trametinib Oral Solution Based on the Palatability Assessment: Remaining After-taste Once Rinsing the Mouth With Water

Participants who received the trametinib oral solution completed a questionnaire to evaluate the palatability of the pediatric formulation. After taking the medication, participants provided feedback on the after-taste of the medication after rinsing with water, rating their experience as very good, good, neither good nor bad, bad or very bad. The ratings of very good, good, and neither good nor bad were grouped together for reporting purposes. (NCT02684058)
Timeframe: Week 1 and Week 5

InterventionParticipants (Count of Participants)
Week 172456173Week 172456174Week 572456173Week 572456174
Very good, good, and neither good nor badBadUnable to answer questionVery BadMissing
LGG Cohort: Dabrafenib and Trametinib15
HGG Cohort: Dabrafenib and Trametinib2
LGG Cohort: Dabrafenib and Trametinib6
LGG Cohort: Dabrafenib and Trametinib9
HGG Cohort: Dabrafenib and Trametinib4
HGG Cohort: Dabrafenib and Trametinib0
LGG Cohort: Dabrafenib and Trametinib2
HGG Cohort: Dabrafenib and Trametinib1
LGG Cohort: Dabrafenib and Trametinib3
HGG Cohort: Dabrafenib and Trametinib3
LGG Cohort: Dabrafenib and Trametinib14

[back to top]

LGG Cohort: Overall Response Rate (ORR) by Central Independent Assessment Using Response Assessment in Neuro-Oncology (RANO) Criteria

"Percentage of participants in the LGG cohort with a best overall confirmed Complete Response (CR) or Partial Response (PR) as assessed per RANO criteria by central independent assessment. The 95% confidence intervals (CIs) were computed using two-sided exact binomial method.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approximately (approx.) 3 years

InterventionPercentage of participants (Number)
LGG Cohort: Dabrafenib and Trametinib46.6
LGG Cohort: Carboplatin and Vincristine10.8

[back to top]

T1/2 for Trametinib

PK parameters were calculated by standard non-compartmental analysis. T1/2 is the elimination half-life (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Interventionhour (Geometric Mean)
HGG Cohort: Dabrafenib and Trametinib26.7
LGG Cohort: Dabrafenib and Trametinib25.7

[back to top]

Tmax for Trametinib

PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Interventionhour (Geometric Mean)
HGG Cohort: Dabrafenib and Trametinib1.67
LGG Cohort: Dabrafenib and Trametinib1.53

[back to top]

All-collected Deaths

On-treatment deaths were collected from 1st dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment (efficacy/survival) follow-up deaths were collected from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG). For participants in the LGG cohort who crossed over to dabrafenib and trametinib, on-treatment deaths were collected from 1st dose to 30 days after last dose of crossover treatment, up to 4.2 years. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up. (NCT02684058)
Timeframe: On-treatment: Up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment: Up to 4.6 years (LGG) and 5.1 years (HGG).Crossover arm: on-treatment: up to 4.2 years

,
InterventionParticipants (Count of Participants)
On- treatment deathsPost-treatment efficacy/survival follow-up deathsCrossover post-treatment efficacy/survival follow-up deathsAll deaths
HGG Cohort: Dabrafenib and Trametinib611017
LGG Cohort: Dabrafenib and Trametinib0000

[back to top]

All-collected Deaths

On-treatment deaths were collected from 1st dose to 30 days after last dose of treatment (or start of crossover treatment), up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment (efficacy/survival) follow-up deaths were collected from 31 days post-treatment to end of study (or start of crossover treatment), up to 4.6 years (LGG) and 5.1 years (HGG). For participants in the LGG cohort who crossed over to dabrafenib and trametinib, on-treatment deaths were collected from 1st dose to 30 days after last dose of crossover treatment, up to 4.2 years. None of the patients who crossed-over were included in the crossover post-treatment efficacy/survival follow-up. (NCT02684058)
Timeframe: On-treatment: Up to 4.2 years (LGG) and 4.1 years (HGG). Post- treatment: Up to 4.6 years (LGG) and 5.1 years (HGG).Crossover arm: on-treatment: up to 4.2 years

InterventionParticipants (Count of Participants)
On- treatment deathsPost-treatment efficacy/survival follow-up deathsCrossover on-treatment deathsCrossover post-treatment efficacy/survival follow-up deathsAll deaths
LGG Cohort: Carboplatin and Vincristine00101

[back to top]

AUClast for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)

PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast). (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

,
Interventionhr * ng/ml (Geometric Mean)
DabrafenibCarboxy-dabrafenibDesmethyl-dabrafenibHydroxy-dabrafenib
HGG Cohort: Dabrafenib and Trametinib43307340035202810
LGG Cohort: Dabrafenib and Trametinib48706420038702980

[back to top]

AUCtau for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)

PK parameters were calculated by standard non-compartmental analysis. AUCtau is the AUC calculated to the end of a dosing interval (tau) at steady-state (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

,
Interventionhr * ng/ml (Geometric Mean)
DabrafenibCarboxy-dabrafenibDesmethyl-dabrafenibHydroxy-dabrafenib
HGG Cohort: Dabrafenib and Trametinib43007120033602840
LGG Cohort: Dabrafenib and Trametinib49106070036602960

[back to top]

Cmax for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)

PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose and 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

,
Interventionng/ml (Geometric Mean)
DabrafenibCarboxy-dabrafenibDesmethyl-dabrafenibHydroxy-dabrafenib
HGG Cohort: Dabrafenib and Trametinib15209050388801
LGG Cohort: Dabrafenib and Trametinib13307210377687

[back to top]

Ctrough for Dabrafenib and Its Metabolites (Carboxy-dabrafenib, Desmethyl-dabrafenib Amd Hydroxy-dabrafenib)

PK parameters were calculated by standard non-compartmental analysis. Ctrough is the pre-dose plasma concentration (NCT02684058)
Timeframe: Week 3 Day 1 pre-dose

,
Interventionng/ml (Geometric Mean)
DabrafenibCarboxy-dabrafenibDesmethyl-dabrafenibHydroxy-dabrafenib
HGG Cohort: Dabrafenib and Trametinib38.0398027541.8
LGG Cohort: Dabrafenib and Trametinib46.0319031044.3

[back to top]

HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria

"Time from first documented response (PR or CR) until disease progression or death as per central independent assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 3.2 years and up to approx. 4.8 years

InterventionMonths (Median)
Up to approx. 3.2 yearsUp to approx. 4.8 years
HGG Cohort: Dabrafenib and Trametinib22.227.4

[back to top]

HGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria

"Time from first documented response (PR or CR) until disease progression or death as per investigator assessment using RANO criteria. CIs were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 3.2 years and up to approx. 4.8 years

InterventionMonths (Median)
Up to approx. 3.2 yearsUp to approx. 4.8 years
HGG Cohort: Dabrafenib and Trametinib26.632.7

[back to top]

HGG Cohort: ORR by Investigator Assessment Using RANO Criteria

"ORR in the HGG cohort defined as the percentage of participants in the HGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 3.2 years and up to approx. 4.8 years

InterventionPercentage of participants (Number)
Up to approx. 3.2 yearsUp to approx. 4.8 years
HGG Cohort: Dabrafenib and Trametinib58.561.0

[back to top]

LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Central Independent Assessment Using RANO Criteria

"Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 3 years and up to approx 4.2 years

,
InterventionMonths (Median)
Up to approx. 3 yearsUp to approx 4.2 years
LGG Cohort: Carboplatin and VincristineNA19.4
LGG Cohort: Dabrafenib and Trametinib20.330.0

[back to top]

LGG Cohort: Kaplan-Meier Estimates of Duration of Response (DOR) as Per Investigator Assessment Using RANO Criteria

"Time from first documented response (PR or CR) until disease progression or death as per RANO criteria. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy, were censored at the date of the last adequate tumor evaluation.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 3 years and up to approx 4.2 years

,
InterventionMonths (Median)
Up to approx. 3 yearsUp to approx 4.2 years
LGG Cohort: Carboplatin and VincristineNA22.5
LGG Cohort: Dabrafenib and TrametinibNA44.4

[back to top]

LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Central Independent Assessment Using RANO Criteria

Time from the date of randomization to the date of first documented disease progression as per central independent review assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. (NCT02684058)
Timeframe: Up to approx. 3 years and up to approx 4.2 years

,
InterventionMonths (Median)
Up to approx. 3 yearsUp to approx 4.2 years
LGG Cohort: Carboplatin and Vincristine7.47.2
LGG Cohort: Dabrafenib and Trametinib20.124.9

[back to top]

LGG Cohort: Kaplan-Meier Progression-Free Survival (PFS) as Per Investigator Assessment Using RANO Criteria

Time from the date of randomization to the date of first documented disease progression as per investigator assessment using RANO criteria or death due to any cause. Confidence Intervals were estimated using the Brookmeyer Crowley method. Patients who had not progressed or died or had received further anticancer therapy were censored at the date of the last adequate tumor evaluation. (NCT02684058)
Timeframe: Up to approx. 3 years and up to approx 4.2 years

,
InterventionMonths (Median)
Up to approx. 3 yearsUp to approx 4.2 years
LGG Cohort: Carboplatin and VincristineNA30.8
LGG Cohort: Dabrafenib and TrametinibNA46.0

[back to top]

LGG Cohort: ORR by Investigator Assessment Using RANO Criteria

"Percentage of participants in the LGG cohort with a best overall confirmed CR or PR as assessed per RANO criteria by investigator assessment. The 95% CIs were computed using two-sided exact binomial method.~CR: Complete disappearance of all enhancing measurable and nonmeasurable disease sustained for at least 4 weeks; no new lesions; and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be off steroids or only on physiologic replacement doses.~PR: ≥ 50% reduction, compared to baseline, in the sum of products of the perpendicular diameters for all measurable lesions for at least 4 weeks, no progression of nonmeasureable disease, no new lesions, and stable or improved nonenhancing (T2/FLAIR) lesions. Patient must be on a corticosteroid dose not greater than the dose at the time of baseline scan and be stable or improving clinically." (NCT02684058)
Timeframe: Up to approx. 3 years and up to approx 4.2 years

,
InterventionPercentage of participants (Number)
Up to approx. 3 yearsUp to approx. 4.2 years
LGG Cohort: Carboplatin and Vincristine13.518.9
LGG Cohort: Dabrafenib and Trametinib54.858.9

[back to top]

LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score

"The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the fatigue interference of the participants. Fatigue item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening fatigue. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated a greater level of reported fatigue.~Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up." (NCT02684058)
Timeframe: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)

InterventionScore on a Scale (Mean)
BaselineWeek 5 Day 1Week 8 Day 1Week 16 Day 1Week 24 Day 1Week 32 Day 1Week 40 Day 1Week 48 Day 1Week 56 Day 1EOTPost Treatment Follow-Up 1Post Treatment Follow-Up 2Post Treatment Follow-Up 3Post Treatment Follow-Up 4Post Treatment Follow-Up 5Post Treatment Follow-Up 6Post Treatment Follow-Up 8
LGG Cohort: Carboplatin and Vincristine54.3756.8858.1057.8155.0257.6658.4953.4857.6356.8852.3662.6248.9448.9448.9455.7848.94

[back to top]

LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Fatigue Score

"The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 1 item measuring the fatigue interference of the participants. Fatigue item used a 5-level Likert scale with 1= never and 5= almost always, higher scores indicate worsening fatigue. Raw scores were then converted into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores indicated a greater level of reported fatigue.~Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the PROMIS Parent Proxy Global 7+2 Health questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up." (NCT02684058)
Timeframe: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)

InterventionScore on a Scale (Mean)
BaselineWeek 5 Day 1Week 8 Day 1Week 16 Day 1Week 24 Day 1Week 32 Day 1Week 40 Day 1Week 48 Day 1Week 56 Day 1Week 72 Day 1Week 88 Day 1Week 104 Day 1Week 120 Day 1Week 136 Day 1Week 152 Day 1Week 168 Day 1EOTPost Treatment Follow-Up 1Post Treatment Follow-Up 2Post Treatment Follow-Up 3Post Treatment Follow-Up 4Post Treatment Follow-Up 5
LGG Cohort: Dabrafenib and Trametinib53.3053.9652.6851.2251.0452.4952.2751.6550.5149.9350.5251.1150.4050.9747.7148.2152.3548.9462.6248.9456.0762.62

[back to top]

LGG Cohort: PROMIS Parent Proxy Global Health 7+2 Scores- Global Health Score

"The PROMIS Parent Proxy Global Health 7+2 was used to evaluate the quality of life of participants. The questionnaire included 7 items measuring the global health of the patient. 4 items used a 5-level Likert scale with 1=poor and 5=excellent; 1 item used a 5-level Likert scale with 1=never and 5=always; and 2 items used a 5-level Likert scale with 1=never and 5=almost always. The total raw global health score, ranging from 7 to 35, was computed by summing item values, with higher scores indicating better overall well-being. Raw scores were then transformed into T-scores, standardized with a mean of 50 and a standard deviation of 10. Higher T-scores reflected better global health status.~Participants who discontinued treatment for reasons other than disease progression entered the post-treatment efficacy follow-up phase, where the questionnaire was performed every 16 weeks until disease progression, withdrawal of consent by patient or a parental/legal guardian, or lost to follow-up." (NCT02684058)
Timeframe: Baseline, and Day 1 of Week 5, 8, 16, 24, 32, 49, 48 and 56, and thereafter every 16 weeks until end of treatment (EOT), EOT, and every 16 weeks in the post-treatment efficacy follow-up phase until disease progression (assessed up to 4.6 years)

InterventionScore on a Scale (Mean)
BaselineWeek 5 Day 1Week 8 Day 1Week 16 Day 1Week 24 Day 1Week 32 Day 1Week 40 Day 1Week 48 Day 1Week 56 Day 1EOTPost Treatment Follow-Up 1Post Treatment Follow-Up 2Post Treatment Follow-Up 3Post Treatment Follow-Up 4Post Treatment Follow-Up 5Post Treatment Follow-Up 6Post Treatment Follow-Up 8
LGG Cohort: Carboplatin and Vincristine42.8939.0638.3641.1136.5740.9638.8441.5638.6639.6945.5339.7034.6043.6037.9036.4537.90

[back to top]

Part 2: Overall Survival

Overall survival was defined as duration from the date of randomization to the date of the participant's death. (NCT02703272)
Timeframe: Up to 4 year and 4 months

InterventionMonths (Median)
Part 2: Ibrutinib+CIT (RICE or RVICI)14.13
Part 2: Chemoimmunotherapy11.07

[back to top]

Part 2: Percentage of Participants With EFS at 2 Years

EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. (NCT02703272)
Timeframe: At 2 years

InterventionPercentage of participants (Number)
Part 2: Ibrutinib+CIT (RICE or RVICI)14.3
Part 2: Chemoimmunotherapy12.5

[back to top]

Part 2: Percentage of Participants Who Achieved Partial Response (PR)

Percentage of participants who achieved PR were assessed. PR was defined as 50% decrease in SPD on computed tomography (CT) or magnetic resonance imaging (MRI); FDG-PET may be positive; no new or PD; morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. (NCT02703272)
Timeframe: Up to 4 year and 4 months

Interventionpercentage of participants (Number)
Part 2: Ibrutinib+CIT (RICE or RVICI)51.4
Part 2: Chemoimmunotherapy62.5

[back to top]

Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionng/mL (Median)
12-17 years
Part 2: Ibrutinib: 240 mg/m^22.93

[back to top]

Part 2: Percentage of Participants Who Achieved Complete Response (CR)

Complete response rate was defined as the percentage of participants who achieved complete response or complete response with an incomplete marrow recovery (CRi) on or prior to initiation of subsequent anti-leukemic therapy per the IRC assessment. (NCT02703272)
Timeframe: Up to 4 year and 4 months

InterventionPercentage of Participants (Number)
Part 2: Ibrutinib+CIT (RICE or RVICI)17.1
Part 2: Chemoimmunotherapy18.8

[back to top]

Part 1 and Part 2: Overall Response Rate (ORR)

ORR was defined as the percentage of participants achieving a best overall response of either complete response (CR) (including CR biopsy-negative [CRb] and unconfirmed CR [CRu]) or partial response (PR) as evaluated by International Pediatric non-Hodgkin lymphoma (NHL) response criteria. CR=disappearance of all disease; CRb=residual mass has no morphologic evidence of disease from limited or core biopsy, with no new lesions by imaging examination; bone marrow (BM) and CSF morphologically free of disease; no new or PD elsewhere, CRu=Residual mass is negative by FDG-PET; no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, PR=50% decrease in SPD on CT or MRI; FDG-PET may be positive (deauville score or 4 or 5 with reduced lesional uptake compared with baseline); no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. (NCT02703272)
Timeframe: Up to 4 year and 4 months

InterventionPercentage of participants (Number)
Part 1: Ibrutinib+RICE81.8
Part 1: Ibrutinib+RVICI50.0
Part 2: Ibrutinib+CIT (RICE or RVICI)68.6
Part 2: Chemoimmunotherapy81.3

[back to top]

Part 2: Number of Participants With c-MYC Gene Rearrangement

Number of participants with c-MYC gene rearrangement were reported. Blood samples were taken to evaluate the levels of biomarker such as c-MYC Gene rearrangement. (NCT02703272)
Timeframe: At baseline (Cycle 1 Day 1)

InterventionParticipants (Count of Participants)
Part 2: Ibrutinib+CIT (RICE or RVICI)1
Part 2: Chemoimmunotherapy1

[back to top]

Part 2: Number of Participants Who Proceeded to Stem Cell Transplantation

Number of participants who proceeded to stem cell transplantation were reported. (NCT02703272)
Timeframe: Up to end of the study (Up to 4 year and 4 months)

InterventionParticipants (Count of Participants)
Part 2: Ibrutinib+CIT (RICE or RVICI)13
Part 2: Chemoimmunotherapy7

[back to top]

Part 2: Event Free Survival (EFS) Between the 2 Treatment Groups

EFS was the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurred first based on blinded independent event review by the Independent Review Committee (IRC). CR was defined as computed tomography (CT) or magnetic resonance imaging (MRI) reveals no residual disease or new lesions, resected residual mass that was pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50 percent (%) decrease in sum of the products of the lesion diameters (SPD) on CT or MRI; fluorodeoxyglucose (FDG)-positron emission tomography (PET) may be positive, no new or progressive disease (PD); morphologic evidence of disease may be present in BM or cerebrospinal fluid (CSF) if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. (NCT02703272)
Timeframe: Time from Randomization to death, disease progression, or lack of CR or PR after 3 cycles of treatment (up to 4 year and 4 months)

InterventionMonths (Median)
Part 2: Ibrutinib+CIT (RICE or RVICI)6.05
Part 2: Chemoimmunotherapy6.97

[back to top]

Part 2: Duration of Response

Duration of response was defined as the duration from date of initial documentation of a response (CR or PR) to the date of first documented evidence of progressive disease (PD) or death, whichever occurred first. PD: >25% increase in SPD of residual lesions (calculated from nadir) on CT or MRI; Deauville score 4 or 5 on FDG-PET with increase in lesional uptake from baseline; documentation of new lesions or development of new morphologic evidence of disease in BM or CSF. (NCT02703272)
Timeframe: Up to 4 year and 4 months

InterventionMonths (Median)
Part 2: Ibrutinib+CIT (RICE or RVICI)6.01
Part 2: Chemoimmunotherapy6.51

[back to top]

Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

,
Interventionmilliliter per hour (mL/h) (Median)
1-5 years6-11 years12-17 years
Part 1: Ibrutinib: 240 mg/m^212201450348
Part 1: Ibrutinib: 329 mg/m^2508805729

[back to top]

Part 1: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionmilliliter per hour (mL/h) (Median)
1-5 years6-11 years
Part 1: Ibrutinib: 440 mg/m^212001300

[back to top]

Part 1 and Part 2: Visual Analog Scale (VAS) Score for Palatability

Palatability of ibrutinib was measured by using a VAS. The scale is a 5-point visual analog scale incorporating a facial hedonic scale designed to span pediatric ages and levels of participant comprehension with a score range of 1 to 5, where 1 represents best score and 5 is worst palatability. (NCT02703272)
Timeframe: Day 1 of Cycle 1 and Cycle 3

,,
InterventionUnits on a scale (Mean)
Cycle 1 Day 1Cycle 3 Day 1
Part 1: Ibrutinib+RICE2.63.3
Part 1: Ibrutinib+RVICI3.22.3
Part 2: Ibrutinib+CIT (RICE or RVICI)2.42.6

[back to top]

Part 1 and Part 2: Gene Expression Evaluated by Disease-specific Biomarkers at Baseline

"Tumor formalin-fixed paraffin-embedded (FFPE) samples were taken to evaluate the baseline gene expression by disease-specific biomarkers such as BCL-2L1 (BCL-xl), BIRC2 (cIAP1), Caspase 3 (CASP3), STAT3, and SYK. Transcripts per million (TPM) is a normalization method for RNA-sequencing, which means for every 1,000,000 RNA molecules in the RNA-sequencing tumor FFPE sample, x came from this gene/transcript." (NCT02703272)
Timeframe: Baseline

,
InterventionTranscripts per million (Mean)
BCL-2L1 (BCL-xl)BIRC2 (cIAP1)Caspase 3 (CASP3)STAT3SYK
Part 2: Chemoimmunotherapy74.3079040.0171647.61412526.35308618.36324
Part 2: Ibrutinib+CIT (RICE or RVICI)58.0934647.2078751.14711540.02256705.29909

[back to top]

Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionng/mL (Median)
1-5 years6-11 years
Part 2: Ibrutinib: 440 mg/m^23.794.15

[back to top]

Part 1 and Part 2: Number of Participants With Greater Than (>) 90% Bruton's Tyrosine Kinase (BTK) Occupancy

Number of participants with >90% BTK occupancy were reported. Blood samples were collected to assess BTK occupancy. (NCT02703272)
Timeframe: Up to 3 months

InterventionParticipants (Count of Participants)
Part 1: Ibrutinib5
Part 2: Ibrutinib5

[back to top]

Part 2: Tumor Volume Reduction Rate at Day 14

The tumor volume reduction rate was defined as percent decrease in the sum of the products of the lesion diameters at Day 14. It was measured as the mean change in the sum of the products of the lesion diameters (SPD) at Day 14. (NCT02703272)
Timeframe: At Day 14

InterventionPercent change (Least Squares Mean)
Part 2: Ibrutinib+CIT (RICE or RVICI)-49.7
Part 2: Chemoimmunotherapy-58.60

[back to top]

Part 2: Number of Participants With CD79B, CARD11, and MYD Mutations

Number of participants with CD79B, CARD11, and MYD mutations were reported. Blood samples were taken to evaluate the levels of biomarkers such as CD79B, CARD11, and MYD mutations. (NCT02703272)
Timeframe: Up to 4 year and 4 months

,
InterventionParticipants (Count of Participants)
CD79BCARD11MYD mutation
Part 2: Chemoimmunotherapy000
Part 2: Ibrutinib+CIT (RICE or RVICI)110

[back to top]

Part 2: Time to Response

Time to response was defined as the time interval from the first dose of ibrutinib to the first documented response for those participants who responded. Time to response was summarized for participants who achieved either CR (including CRb and CRu) or PR. CR=disappearance of all disease; CRb=residual mass has no morphologic evidence of disease from limited or core biopsy, with no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, CRu=Residual mass is negative by FDG-PET; no new lesions by imaging examination; BM and CSF morphologically free of disease; no new or PD elsewhere, PR=50% decrease in SPD on CT or MRI; FDG-PET may be positive (deauville score or 4 or 5 with reduced lesional uptake compared with baseline); no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. (NCT02703272)
Timeframe: Up to 4 Years and 4 months

InterventionMonths (Median)
Part 2: Ibrutinib+CIT (RICE or RVICI)0.89
Part 2: Chemoimmunotherapy0.82

[back to top]

Part 2: Percentage of Participants With EFS at 3 Years

EFS is the time interval from randomization to death, disease progression, or lack of complete response (CR) or partial response (PR) after 3 cycles of treatment, whichever occurs first based on blinded independent event review by the IRC. CR was defined as CT or MRI reveals no residual disease or new lesions, resected residual mass that is pathologically (morphologically) negative for disease, BM and CSF morphologically free of disease with no new lesions by imaging examination. PR was defined as 50% decrease in um of the products of the SPD on CT or MRI; FDG-PET may be positive, no new or PD; morphologic evidence of disease may be present in BM or CSF if present at diagnosis; however, there should be 50% reduction in percentage of lymphoma cells. (NCT02703272)
Timeframe: At 3 years

InterventionPercentage of participants (Number)
Part 2: Ibrutinib+CIT (RICE or RVICI)8.6
Part 2: Chemoimmunotherapy12.5

[back to top]

Part 1 and Part 2: Number of Participants With Adverse Events as Measure of Safety and Tolerability

An AE is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. (NCT02703272)
Timeframe: Up to 4 year and 4 months

InterventionParticipants (Count of Participants)
Part 1: Ibrutinib+RICE11
Part 1: Ibrutinib+RVICI10
Part 2: Ibrutinib+CIT (RICE or RVICI)35
Part 2: Chemoimmunotherapy15

[back to top]

Part 2: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionng/mL (Median)
12-17 years18+ years
Part 2: Ibrutinib: 329 mg/m^24.863.7

[back to top]

Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionliter(s) (Median)
1-5 years6-11 years
Part 2: Ibrutinib: 440 mg/m^21.686.18

[back to top]

Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

AUC is defined as area under the plasma concentration-time curve. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionh*ng/mL (Mean)
12-17 years18+ years
Part 2: Ibrutinib: 329 mg/m^2499423

[back to top]

Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

AUC is defined as area under the plasma concentration-time curve. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionh*ng/mL (Mean)
1-5 years6-11 years
Part 2: Ibrutinib: 440 mg/m^2298655

[back to top]

Part 2: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

AUC is defined as area under the plasma concentration-time curve. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionh*ng/mL (Mean)
12-17 years
Part 2: Ibrutinib: 240 mg/m^2:215

[back to top]

Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionliter(s) (Median)
12-17 years18+ years
Part 2: Ibrutinib: 329 mg/m^24.149.29

[back to top]

Part 2: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionliter(s) (Median)
12-17 years
Part 2: Ibrutinib: 240 mg/m^29.9

[back to top]

Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

InterventionmL/h (Median)
12-17 years18+ years
Part 2: Ibrutinib: 329 mg/m^29821510

[back to top]

Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

InterventionmL/h (Median)
1-5 years6-11 years
Part 2: Ibrutinib: 440 mg/m^21110856

[back to top]

Part 2: Apparent (Oral) Plasma Clearance (CL/F) of Ibrutinib

CL/F is defined as apparent plasma clearance of ibrutinib. As per planned analyses, PK parameters for Part 2 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

InterventionmL/h (Median)
12-17 years
Part 2: Ibrutinib: 240 mg/m^21730

[back to top]

Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionnanograms per milliliter (ng/mL) (Median)
1-5 years6-11 years
Part 1: Ibrutinib: 440 mg/m^25.073.88

[back to top]

Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

AUC is defined as area under the plasma concentration-time curve. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 milligrams per meter square [mg/m^2], 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

,
Interventionhours*nanogram per milliliter (h*ng/mL) (Median)
1-5 years6-11 years12-17 years
Part 1: Ibrutinib: 240 mg/m^21431451210
Part 1: Ibrutinib: 329 mg/m^2386349661

[back to top]

Part 1: Area Under the Plasma Concentration-time Curve (AUC) of Ibrutinib

AUC is defined as area under the plasma concentration-time curve. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 milligrams per meter square [mg/m^2], 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionhours*nanogram per milliliter (h*ng/mL) (Median)
1-5 years6-11 years
Part 1: Ibrutinib: 440 mg/m^2310324

[back to top]

Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

,
Interventionliter(s) (Median)
1-5 years6-11 years12-17 years
Part 1: Ibrutinib: 240 mg/m^211.1183.63
Part 1: Ibrutinib: 329 mg/m^25.187.5511.3

[back to top]

Part 1: Maximum Observed Plasma Concentration (Cmax) of Ibrutinib

Cmax is defined as maximum plasma concentration of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

,
Interventionnanograms per milliliter (ng/mL) (Median)
1-5 years6-11 years12-17 years
Part 1: Ibrutinib: 240 mg/m^23.863.464.88
Part 1: Ibrutinib: 329 mg/m^24.483.644.73

[back to top]

Part 1: Apparent (Oral) Volume of Distribution (Vd/F) of Ibrutinib

Vd/F is defined as apparent (oral) volume of distribution of ibrutinib. As per planned analyses, pharmacokinetic (PK) parameters for Part 1 were presented per dose group (240 mg/m^2, 329 mg/m^2 and 440 mg/m^2) and age group (1-5, 6-11, 12-17 and >18 years). As planned in protocol, the PK parameters were presented per dose group as dosing was dependent on age. (NCT02703272)
Timeframe: Up to Cycle 3 (each cycle of 21 or 28 days)

Interventionliter(s) (Median)
1-5 years6-11 years
Part 1: Ibrutinib: 440 mg/m^27.6319

[back to top]

Overall Survival

"Overall survival is defined as the time from randomization until death. In the event that no death was documented prior to study termination or analysis cutoff, OS was censored at the last known date the subject was known to be alive, either through completion of on-study visits or through survival follow-up contact.~The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology).~The Kaplan-Meier curves were also plotted. A Cox proportional hazard model with an adjustment for tumor histology (biphasic vs sarcomatoid) was used to compute the estimated hazard ratio and two-sided 95% CI. The treatment effect on OS was evaluated using the stratified log-rank test (stratified by tumor histology). The significance level to be used in the OS analysis at the final analysis was based on α = 0.04999 (two-sided)." (NCT02709512)
Timeframe: 18 months

Interventionmonths (Median)
Drug: ADI-PEG 20 Plus Pem Platinum9.30
Drug: Placebo Plus Pem Platinum7.66

[back to top]

Progression Free Survival

The key secondary endpoint for the phase 3 portion is PFS, which will be analyzed only if the analysis of OS is statistically significant at the final analysis, with alpha level of 0.05 (two-sided) using the same statistical methodologies as applied to OS. (NCT02709512)
Timeframe: approximately 18 months

Interventionmonths (Median)
Drug: ADI-PEG 20 Plus Pem Platinum6.24
Drug: Placebo Plus Pem Platinum5.65

[back to top]

Response Rate

"Objective Response Rate is calculated as the proportion of subjects whose best tumor response from all post-baseline tumor assessments is complete response (CR) or partial response (PR). The best tumor response is the best response recorded from the start of the treatment until the end of treatment taking into account any requirement for confirmation.~To test Objective Response Rate significance, a Relative Risk Ratio (ADI-PEG 20 / Placebo) was calculated as the common relative risk of having a response (CR or PR) based on the Mantel-Haenszel estimator controlling for tumor histology (biphasic versus sarcomatoid)." (NCT02709512)
Timeframe: approximately 18 months

InterventionParticipants (Count of Participants)
Drug: ADI-PEG 20 Plus Pem Platinum12
Drug: Placebo Plus Pem Platinum12

[back to top]

Overall Survival Phase 3 Interim Analysis

"The primary analysis of OS Phase 3 was performed at the interim analysis. This was performed once 50% of the planned OS events for phase 3 have occurred (ie, 169 of the 338 planned OS events). This interim analysis will evaluate OS in the ITT population in an unblinded manner. The OS data at the second interim analysis will be analyzed to support the following decisions:~Futility stopping: Terminate the study due to futility at the interim analysis. Sample size re-estimation: Increase the target number of OS events after the second interim analysis.. The treatment effect on OS will be evaluated using the stratified log-rank test (stratified by tumor histology)." (NCT02709512)
Timeframe: Approximately 18 months

Interventionmonths (Median)
Drug: ADI-PEG 20 Plus Pem Platinum9.82
Drug: Placebo Plus Pem Platinum7.49

[back to top]

Progression Free Survival (PFS)

The length of time from treatment initiation to progression of disease (at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression) as assessed by RECIST 1.1. (NCT02710396)
Timeframe: Up to 2 years

Interventionmonths (Median)
Cohort 14.80
Cohort 23.94

[back to top]

Number of Subjects With NSCLC Who Achieved DCB

Objective response to study treatment will be assessed by RECIST 1.1 by a study radiologist. Partial and complete responses will be confirmed by a repeat imaging occurring at least 4 weeks after the initial identification of response; unconfirmed responses will be considered stable or progressive disease dependent on results of the second CT scan. Durable clinical benefit (DCB) will be defined as stable disease (Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study), OR complete response (disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.), OR partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) lasting longer than 6 months. (NCT02710396)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Cohort 13
Cohort 20
Cohort 30

[back to top]

Objective Response Rate (ORR)

ORR is defined as participants with a partial (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) or complete response (Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm) as assessed by RECIST 1.1 criteria. (NCT02710396)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Cohort 14
Cohort 21
Cohort 30

[back to top]

Overall Survival (OS)

The length of time from the start of treatment to death. (NCT02710396)
Timeframe: Up to 28 months

InterventionMonths (Median)
Cohort 114.06
Cohort 223.49

[back to top]

Number of Subjects With Major Pathologic Response (MPR)

Major pathologic response rate (MPR) is defined as > or = 90% decrease in viable tumor. (NCT02716038)
Timeframe: 84 days

InterventionParticipants (Count of Participants)
MPDL3280A, Carboplatin, Nab-paclitaxel17

[back to top]

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Carboplatin (Total and Free)

Cmax is maximum plasma concentration of carboplatin. The LLQ of carboplatin was 100.0 ng/mL. (NCT02718417)
Timeframe: Pre-dose and at 0.5, 1, 5, 6, 10, and 24 hours post carboplatin infusion on Day 1 of Cycle 2

,,
Interventionng/mL (Geometric Mean)
Total CarboplatinFree Carboplatin
PK: Chemotherapy + Avelumab Followed by Avelumab1835015350
PK: Chemotherapy Followed by Avelumab2358021740
PK: Chemotherapy Followed by Observation1899017090

[back to top]

Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Carboplatin (Total and Free)

AUCinf is the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. (NCT02718417)
Timeframe: Pre-dose and at 0.5, 1, 5, 6, 10, and 24 hours post carboplatin infusion on Day 1 of Cycle 2

,,
Interventionng*hr/mL (Geometric Mean)
Total CarboplatinFree Carboplatin
PK: Chemotherapy + Avelumab Followed by Avelumab10050052000
PK: Chemotherapy Followed by Avelumab8760055840
PK: Chemotherapy Followed by Observation9043052300

[back to top]

Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment

Vital signs included blood pressure and pulse rate. Blood pressure included sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP). MP is applicable only for two arms 'Chemotherapy followed by Avelumab' and 'Chemotherapy + Avelumab followed by Avelumab'. OP is applicable only for third arm 'Chemotherapy followed by Observation'. Category titles 'MP/OP' imply which ever phase was applicable for the respective reporting arms. (NCT02718417)
Timeframe: Baseline, first 3 months of Chemotherapy Phase (CP): Day 1 of Cycles 2, 3 and 4 (each cycle 21 days); Maintenance/Observation Phase (MP/OP): Days 1, 15 and 29 of Cycles 1 and 2 (each cycle 42 days) and at end of treatment (up to 27 months)

,
Interventionmillimeters of mercury (Mean)
CP: Change at Day 1, Cycle 2: Sitting DBPCP: Change at Day 1, Cycle 3: Sitting DBPCP: Change at Day 1, Cycle 4: Sitting DBPMP/OP: Change at Day 1, Cycle 1: Sitting DBPMP/OP: Change at Day 15, Cycle 1: Sitting DBPMP/OP: Change at Day 29, Cycle 1: Sitting DBPMP/OP: Change at Day 1, Cycle 2: Sitting DBPMP/OP: Change at Day 15, Cycle 2: Sitting DBPMP/OP: Change at Day 29, Cycle 2: Sitting DBPChange at EOT : Sitting DBPCP: Change at Day 1, Cycle 2: Sitting SBPCP: Change at Day 1, Cycle 3: Sitting SBPCP: Change at Day 1, Cycle 4: Sitting SBPMP/OP: Change at Day 1, Cycle 1: Sitting SBPMP/OP: Change at Day 15, Cycle 1: Sitting SBPMP/OP: Change at Day 29, Cycle 1: Sitting SBPMP/OP: Change at Day 1, Cycle 2: Sitting SBPMP/OP: Change at Day 15, Cycle 2: Sitting SBPMP/OP: Change at Day 29, Cycle 2: Sitting SBPChange at EOT: Sitting SBP
Chemotherapy + Avelumab Followed by Avelumab0.100.50-0.50-1.30-1.80-1.80-1.70-2.40-1.900.000.70-0.300.10-1.60-3.20-2.80-0.60-3.90-2.90-1.00
Chemotherapy Followed by Avelumab0.00-0.50-0.10-2.20-2.10-1.70-2.30-2.00-2.60-0.702.301.501.00-1.80-1.10-2.20-1.20-2.10-2.701.70

[back to top]

Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment

Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized. MP is applicable only for two arms 'Chemotherapy followed by Avelumab' and 'Chemotherapy + Avelumab followed by Avelumab'. OP is applicable only for third arm 'Chemotherapy followed by Observation'. Category titles 'MP/OP' imply which ever phase was applicable for the respective reporting arms. (NCT02718417)
Timeframe: Baseline, first 3 months of Chemotherapy Phase (CP): Day 1 of Cycles 2, 3 and 4 (each cycle 21 days); Maintenance/Observation Phase (MP/OP): Days 1, 15 and 29 of Cycles 1 and 2 (each cycle 42 days) and at end of treatment (up to 27 months)

,
Interventionbeats per minute (Mean)
CP: Change at Day 1, Cycle 2CP: Change at Day 1, Cycle 3CP: Change at Day 1, Cycle 4MP/OP: Change at Day 1, Cycle 1MP/OP: Change at Day 15, Cycle 1MP/OP: Change at Day 29, Cycle 1MP/OP: Change at Day 1, Cycle 2MP/OP: Change at Day 15, Cycle 2MP/OP: Change at Day 29, Cycle 2Change at EOT
Chemotherapy + Avelumab Followed by Avelumab1.802.901.90-0.10-2.40-3.60-4.70-4.90-5.20-1.50
Chemotherapy Followed by Avelumab-0.5-0.20-0.30-1.90-2.90-3.10-3.50-5.10-5.60-1.60

[back to top]

Change From Baseline in Vital Signs - Pulse Rate at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment

Vital signs included blood pressure and pulse rate. Changes from baseline in sitting pulse rate were summarized. MP is applicable only for two arms 'Chemotherapy followed by Avelumab' and 'Chemotherapy + Avelumab followed by Avelumab'. OP is applicable only for third arm 'Chemotherapy followed by Observation'. Category titles 'MP/OP' imply which ever phase was applicable for the respective reporting arms. (NCT02718417)
Timeframe: Baseline, first 3 months of Chemotherapy Phase (CP): Day 1 of Cycles 2, 3 and 4 (each cycle 21 days); Maintenance/Observation Phase (MP/OP): Days 1, 15 and 29 of Cycles 1 and 2 (each cycle 42 days) and at end of treatment (up to 27 months)

Interventionbeats per minute (Mean)
CP: Change at Day 1, Cycle 2CP: Change at Day 1, Cycle 3CP: Change at Day 1, Cycle 4MP/OP: Change at Day 1, Cycle 1MP/OP: Change at Day 15, Cycle 1MP/OP: Change at Day 29, Cycle 1MP/OP: Change at Day 1, Cycle 2Change at EOT
Chemotherapy Followed by Observation-0.70-0.0-0.30-0.70-11.70-4.00-3.40-3.70

[back to top]

Functional Assessment of Ovarian Symptom Index- 18 (FOSI-18) Score

National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (FOSI-18) is an 18-itemed participant completed questionnaire, designed to assess impact of cancer therapy on ovarian cancer-related symptoms. Based on numerical point scoring of symptoms. Includes three subscales: disease-related symptoms (10 items), treatment-related side effects (5) and general function/well-being (3). Participants rated their level of symptoms for each items using 5-point scale from 0=not at all to 4=very much. Items that were negatively framed, scores were reversed for analysis so that higher scores= good quality of life. Total symptom index: total of 18 scores, ranging from 0=severely symptomatic to 72=asymptomatic. Higher FOSI-18 scores= better functioning or lower symptom burden. MP applicable only for arms 'Chemotherapy followed by Avelumab' and 'Chemotherapy + Avelumab followed by Avelumab' and OP for 'Chemotherapy followed by Observation'. (NCT02718417)
Timeframe: CP: Pre-dose on Day 1 of Cycles 2 to 6 (1 cycle= 21 days); MP/OP: Day 1 of Cycles 1 to 12 (1 cycle= 42 days), End of treatment (any time up to Month 27)

,,
Interventionunits on a scale (Mean)
CP: Day 1, Cycle 2CP: Day 1, Cycle 3CP: Day 1, Cycle 4CP: Day 1, Cycle 5CP: Day 1, Cycle 6MP/OP: Day 1, Cycle 1MP/OP: Day 1, Cycle 2MP/OP: Day 1, Cycle 3MP/OP: Day 1, Cycle 4MP/OP: Day 1, Cycle 5MP/OP: Day 1, Cycle 6MP/OP: Day 1, Cycle 7MP/OP: Day 1, Cycle 8MP/OP: Day 1, Cycle 9MP/OP: Day 1, Cycle 10MP/OP: Day 1, Cycle 11MP/OP: Day 1, Cycle 12End of treatment
Chemotherapy + Avelumab Followed by Avelumab53.8854.1054.3154.5354.7454.9655.3955.8256.2556.6957.1257.5557.9858.4158.8459.2859.7156.01
Chemotherapy Followed by Avelumab54.3354.6154.8855.1655.4355.7056.2556.8057.3557.9058.4559.0059.5560.0960.6461.1961.7457.04
Chemotherapy Followed by Observation54.2754.5154.7554.9955.2355.4755.9556.4356.9157.3957.8758.3658.8459.3259.8060.2860.7656.64

[back to top]

Percentage of Participants With Objective Response as Assessed by Blinded Independent Central Review (BICR)

BICR assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of CR or PR. CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. (NCT02718417)
Timeframe: Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months)

Interventionpercentage of participants (Number)
Chemotherapy Followed by Avelumab30.4
Chemotherapy + Avelumab Followed by Avelumab36.0
Chemotherapy Followed by Observation30.4

[back to top]

Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Carboplatin (Total and Free)

AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose. (NCT02718417)
Timeframe: Pre-dose (0 hour), 0.5, 1, 5, 6, 10, and 24 hours post carboplatin infusion on Day 1 of Cycle 2

,,
Interventionng*hr/mL (Geometric Mean)
Total CarboplatinFree Carboplatin
PK: Chemotherapy + Avelumab Followed by Avelumab8410052100
PK: Chemotherapy Followed by Avelumab8438056880
PK: Chemotherapy Followed by Observation8096052590

[back to top]

Number of Participants With Positive Programmed Death Receptor-1 Ligand-1 (PD-L1) Biomarker Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)

PD-L1 assessment was performed using immunohistochemistry. Participants were considered positive if their pretreatment tumor tissue sample demonstrated cell surface PD-L1 expression greater than or equal to (>=) 1 percent (%) tumor cells or >= 5% immune cells and were otherwise considered negative. (NCT02718417)
Timeframe: Up to 36 months

InterventionParticipants (Count of Participants)
Chemotherapy Followed by Avelumab158
Chemotherapy + Avelumab Followed by Avelumab160
Chemotherapy Followed by Observation169

[back to top]

Number of Participants With Treatment-Emergent Adverse Events (AEs) Graded Based on, National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI-CTCAE version 4.03, Grade 1: asymptomatic or mild symptoms, clinical or diagnostic observations only, intervention not indicated; Grade 2: moderate, minimal, local or noninvasive intervention indicated, limiting age-appropriate instrumental activities of daily life (ADL); Grade 3: severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Treatment-emergent events are events between first dose of study drug and up to 36 months that were absent before treatment or that worsened relative to pretreatment state. (NCT02718417)
Timeframe: Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 36 months)

,,
InterventionParticipants (Count of Participants)
Grade 1Grade 2Grade 3Grade 4Grade 5
Chemotherapy + Avelumab Followed by Avelumab1377148846
Chemotherapy Followed by Avelumab1189151675
Chemotherapy Followed by Observation1596131763

[back to top]

Number of Participants With Neutralizing Antibodies (nAb) Against Avelumab by Never and Ever Positive Status

"nAb against avelumab in serum samples was determined and reported separately for nAb never-positive and nAb ever-positive participants. Participants were considered nAb ever-positive if they had at least one positive nAb results (less than or equal to cut point of 0.710 in qualitative competitive ligand binding assay) at any time point during 36 months. nAb never-positive participants were those who had at least one negative nAb results (greater than cut point of 0.710 in qualitative competitive ligand binding assay) at any time point. Data for this outcome measure was not planned to be collected and analyzed for reporting arm Chemotherapy followed by Observation, since, avelumab was not administered in this arm." (NCT02718417)
Timeframe: Up to 36 months

,
InterventionParticipants (Count of Participants)
Never-positiveEver-positive
Immunogenicity: Chemotherapy + Avelumab Followed by Avelumab28246
Immunogenicity: Chemotherapy Followed by Avelumab25616

[back to top]

Number of Participants With Laboratory Abnormalities Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute Common Terminology Criteria (NCI-CTCAE), Version 4.03

As per NCI-CTCAE v 4.03, Grade 3 and above criteria were; Hematology [Anemia - Grade 3: hemoglobin <8.0 grams per deciliter (g/dL), <4.9 millimoles per liter (mmol/L), <80 grams per liter (g/L), transfusion indicated, Grade 4: life-threatening consequences, urgent intervention indicated, Grade 5: death; platelet count decreased- Grade 3:<50.0 to 25.0*10^9/Liters(L), Grade 4: <25.0*10^9/L; lymphocyte count decreased-Grade 3: <0.5-0.2*10^9/L, Grade 4: <0.2*10^9/L; neutrophil count decreased-Grade 3: <1.0 to 0.5*10^9 /L, Grade 4: <0.5*10^9/L]. Chemistry [creatinine increased-Grade 3: >3.0 to 6.0*upper limit of normal (ULN), Grade 4: >6.0*ULN; serum amylase increased, lipase increased-Grade 3: >2.0 - 5.0*ULN, Grade 4: >5.0*ULN]. Liver function [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)-Grade 3: >5.0 to 20.0*ULN, Grade 4: >20.0*ULN]. (NCT02718417)
Timeframe: Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

,,
InterventionParticipants (Count of Participants)
AnemiaPlatelet Count DecreasedLymphocyte Count DecreasedNeutrophil Count DecreasedCreatinine IncreasedSerum Amylase IncreasedLipase IncreasedALT or AST
Chemotherapy + Avelumab Followed by Avelumab68356315979241
Chemotherapy Followed by Avelumab73203514425190
Chemotherapy Followed by Observation633829156010110

[back to top]

Number of Participants With Electrocardiogram (ECG) Abnormalities

ECG abnormalities included: 1) QT interval, QT interval corrected using Bazett's formula (QTcB) and QT interval corrected using Fridericia's formula (QTcF): increase from baseline greater than (>) 30 millisecond (ms) or 60 ms; absolute value > 450 ms, >480 ms and > 500 ms; 2) heart rate (HR) : absolute value <=50 bpm and decrease from baseline >=20 bpm; absolute value >=120 beats per minute (bpm) and increase from baseline >=20 bpm; 3) PR interval: absolute value >=220 ms and increase from baseline >=20 ms; 4) QRS interval: absolute value >= 120 ms. (NCT02718417)
Timeframe: Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

,,
InterventionParticipants (Count of Participants)
QT increase from baseline >30 msQT increase from baseline >60 msQT >450 msQT >480 msQT >500 msQTcB increase from baseline >30 msQTcB increase from baseline >60 msQTcB >450 msQTcB >480 msQTcB >500 msQTcF increase from baseline >30 msQTcF increase from baseline >60 msQTcF >450 msQTcF >480 msQTcF >500 msHeart rate <=50 bpm and decrease >= 20 bpmHeart rate >=120 bpm and increase >= 20 bpmPR >=220 ms and increase from baseline >=20 msQRS >=120 ms
Chemotherapy + Avelumab Followed by Avelumab15260301061373818563291253483251111069
Chemotherapy Followed by Avelumab1283112211071913529169014441061777
Chemotherapy Followed by Observation106352075116251653217891753151136616

[back to top]

Maintenance Progression-Free Survival (PFS) as Assessed by Investigator

Investigator assessed maintenance PFS was defined as the time from Cycle 1 Day 1 of the maintenance phase to the date of the first documentation of PD or death due to any cause, whichever occurs first. It was defined, for participants who proceeded to maintenance phase and who did not have disease progression by investigator during the chemotherapy phase. As per RECIST version 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method (NCT02718417)
Timeframe: From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months)

Interventionmonths (Median)
Chemotherapy Followed by Avelumab10.4
Chemotherapy + Avelumab Followed by Avelumab11.6
Chemotherapy Followed by Observation12.7

[back to top]

Maintenance Phase: Predose Plasma Concentration (Ctrough) of Avelumab

"Ctrough is the concentration at the end of the dosing interval when avelumab was given as a Q2W regimen in the absence of carboplatin and paclitaxel following 1 cycle of avelumab dosing, i.e. before administration of drug on Day 1 of cycle 2. Ctrough of Avelumab in the absence of chemotherapy (i.e. in the maintenance phase) has been reported. The LLQ of avelumab was 0.20 micro-gram per milliliter (mcg/mL). Data for this outcome measure was not reported for reporting arms PK: Chemotherapy + Avelumab followed by Avelumab (since data was not planned to be collected 1 cycle after the initiation of avelumab dosing ) and PK: Chemotherapy followed by Observation (since avelumab was not administered in this arm and therefore data collection was not planned)." (NCT02718417)
Timeframe: Pre-dose (0 hour) on Day 1 of Cycle 2

Interventionmcg/mL (Geometric Mean)
PK: Chemotherapy Followed by Avelumab29.18

[back to top]

Maintenance Phase: Maximum Plasma Concentration (Cmax) of Avelumab

"Cmax is the concentration at the end of a 1 hour infusion, corresponding to the maximum plasma concentration of avelumab. The LLQ of avelumab was 0.20 mcg/mL. Data for this outcome measure was not reported for reporting arms PK: Chemotherapy + Avelumab followed by Avelumab(since data was not planned to be collected 1 cycle after the initiation of avelumab dosing ) and PK: Chemotherapy followed by Observation (since avelumab was not administered in this arm and therefore data collection was not planned)." (NCT02718417)
Timeframe: End of avelumab infusion on Day 1 of Cycle 2

Interventionmcg/mL (Geometric Mean)
PK: Chemotherapy Followed by Avelumab205.6

[back to top]

Number of Participants With Anti-Drug Antibodies (ADA) Against Avelumab by Never and Ever Positive Status

"ADA against avelumab in serum samples was determined and reported separately for ADA never-positive and ADA ever-positive participants. Participants were considered ADA ever-positive if they had at least one positive (ADA titer greater than or equal to 60 with assay cut point of 1.12) ADA result at any time point during 36 months and were otherwise considered negative. Data for this outcome measure was not planned to be collected and analyzed for reporting arm Chemotherapy followed by Observation, since, avelumab was not administered in this arm." (NCT02718417)
Timeframe: Up to 36 months

,
InterventionParticipants (Count of Participants)
Never-positiveEver-positve
Immunogenicity: Chemotherapy + Avelumab Followed by Avelumab197131
Immunogenicity: Chemotherapy Followed by Avelumab23141

[back to top]

Duration of Response (DOR) as Assessed by Investigator

Investigator assessed DOR: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm. PR: at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method. (NCT02718417)
Timeframe: First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Interventionmonths (Median)
Chemotherapy Followed by Avelumab10.6
Chemotherapy + Avelumab Followed by AvelumabNA
Chemotherapy Followed by Observation15.4

[back to top]

Duration of Response (DOR) as Assessed by Blinded Independent Central Review (BICR)

BICR assessed DOR: time (in months) from the first documentation of objective response (confirmed CR or PR) to the date of first documentation of PD or death due to any cause. As per RECIST version 1.1, CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm. PR: at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method. (NCT02718417)
Timeframe: First response subsequently confirmed to progression of disease or start of new anti-cancer therapy or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Interventionmonths (Median)
Chemotherapy Followed by Avelumab11.9
Chemotherapy + Avelumab Followed by Avelumab14.5
Chemotherapy Followed by ObservationNA

[back to top]

Chemotherapy Phase: Predose Plasma Concentration (Ctrough) of Avelumab When Given With Paclitaxel and Carboplatin

"Ctrough is the concentration at the end of the dosing interval when avelumab was given as a Q2W regimen in the absence of carboplatin and paclitaxel following 1 cycle of avelumab dosing, i.e. before administration of drug on Day 1 of cycle 2. The LLQ of avelumab was 0.20 mcg/mL. Data for this outcome measure was not reported for reporting arms PK: Chemotherapy followed by Avelumab (data not available for this OM as avelumab was not given along with paclitaxel and carboplatin in this arm) and PK: Chemotherapy followed by Observation (since avelumab was not administered in this arm and therefore data collection was not planned)." (NCT02718417)
Timeframe: Pre-dose (0 hour) on Day 1 of Cycle 2

Interventionmcg/mL (Geometric Mean)
PK: Chemotherapy + Avelumab Followed by Avelumab3.607

[back to top]

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once Every Three Weeks [Q3W] Regimen)

Cmax is maximum plasma concentration of paclitaxel. The LLQ of paclitaxel was 10.0 ng/mL. (NCT02718417)
Timeframe: Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2

Interventionng/mL (Geometric Mean)
PK: Chemotherapy Followed by Avelumab5646
PK: Chemotherapy + Avelumab Followed by Avelumab4775
PK: Chemotherapy Followed by Observation4694

[back to top]

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Paclitaxel (Once a Week [QW] Regimen)

Cmax is maximum plasma concentration of paclitaxel. The LLQ of paclitaxel was 10.0 ng/mL. (NCT02718417)
Timeframe: Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2

Interventionng/mL (Geometric Mean)
PK: Chemotherapy Followed by Avelumab2880
PK: Chemotherapy + Avelumab Followed by Avelumab2678
PK: Chemotherapy Followed by Observation2649

[back to top]

Chemotherapy Phase: Maximum Plasma Concentration (Cmax) of Avelumab When Given With Paclitaxel and Carboplatin

"Cmax is the concentration at the end of a 1 hour infusion, corresponding to the maximum plasma concentration of avelumab. The LLQ of avelumab was 0.20 mcg/mL. Data for this outcome measure was not reported for reporting arms PK: Chemotherapy followed by Avelumab (data not available for this OM as avelumab was not given along with paclitaxel and carboplatin in this arm) and PK: Chemotherapy followed by Observation (since avelumab was not administered in this arm and therefore data collection was not planned)." (NCT02718417)
Timeframe: End of infusion on Day 1 of Cycle 2

Interventionmcg/mL (Geometric Mean)
PK: Chemotherapy + Avelumab Followed by Avelumab162.9

[back to top]

Number of Participants With Positive Tumor-Infiltrating Cluster of Differentiation 8 (CD8+) T Lymphocytes Expression in Tumor Tissue as Assessed by Immunohistochemistry (IHC)

CD8 assessment was performed using immunohistochemistry. Participants were considered positive if their pre-treatment tumor tissue sample demonstrated >= 1% CD8 positive cells and were otherwise considered negative. (NCT02718417)
Timeframe: Up to 36 months

InterventionParticipants (Count of Participants)
Chemotherapy Followed by Avelumab107
Chemotherapy + Avelumab Followed by Avelumab107
Chemotherapy Followed by Observation118

[back to top]

Overall Survival

Overall survival was defined as the time (in months) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact. Analysis was performed using Kaplan-Meier method. (NCT02718417)
Timeframe: Baseline to discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Interventionmonths (Median)
Chemotherapy Followed by AvelumabNA
Chemotherapy + Avelumab Followed by AvelumabNA
Chemotherapy Followed by ObservationNA

[back to top]

Maintenance Progression-Free Survival as Assessed by Blinded Independent Central Review (BICR)

BICR assessed maintenance PFS was defined as the time from Cycle 1 Day 1 of the maintenance phase to the date of the first documentation of PD or death due to any cause, whichever occurs first. It was defined, for participants who proceeded to maintenance phase and who did not have disease progression by BICR during the chemotherapy phase. As per RECIST version 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method. (NCT02718417)
Timeframe: From Day 1 of Cycle 1 (42 days) of maintenance phase to progression of disease or death, whichever occurred first (maximum duration of 27 months)

Interventionmonths (Median)
Chemotherapy Followed by Avelumab13.6
Chemotherapy + Avelumab Followed by Avelumab13.8
Chemotherapy Followed by ObservationNA

[back to top]

Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (QW Regimen)

AUCinf is the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. (NCT02718417)
Timeframe: Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2

Interventionnanogram*hour per milliliter (ng*hr/mL) (Geometric Mean)
PK: Chemotherapy Followed by Avelumab5138
PK: Chemotherapy + Avelumab Followed by Avelumab4997
PK: Chemotherapy Followed by Observation4921

[back to top]

Percentage of Participants With Objective Response as Assessed by Investigator

Investigator assessed objective response according to RECIST version 1.1, was defined as participants with confirmed best overall response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target and non-target lesions, and sustained for at least 4 weeks. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 mm. PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as reference the baseline sum longest dimensions. (NCT02718417)
Timeframe: Baseline to progression of disease, start of new anti-cancer therapy or discontinuation from study or death, whichever occurred first (maximum duration of 27 months)

Interventionpercentage of participants (Number)
Chemotherapy Followed by Avelumab25.9
Chemotherapy + Avelumab Followed by Avelumab31.1
Chemotherapy Followed by Observation27.8

[back to top]

Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (Q3W Regimen)

AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24). (NCT02718417)
Timeframe: Pre-dose (0 hour), 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2

Interventionng*hr/mL (Geometric Mean)
PK: Chemotherapy Followed by Avelumab17540
PK: Chemotherapy + Avelumab Followed by Avelumab15870
PK: Chemotherapy Followed by Observation16390

[back to top]

Chemotherapy Phase: Area Under the Concentration Time Curve From Time Zero to 24 Hours (AUC24) of Paclitaxel (QW Regimen)

AUC24 is the area under the plasma concentration versus time curve from time zero (pre-dose) to 24 hours post-dose (0 to 24). (NCT02718417)
Timeframe: Pre-dose (0 hour), 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2

Interventionng*hr/mL (Geometric Mean)
PK: Chemotherapy Followed by Avelumab4960
PK: Chemotherapy + Avelumab Followed by Avelumab4572
PK: Chemotherapy Followed by Observation4304

[back to top]

Chemotherapy Phase: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUCinf) of Paclitaxel (Q3W Regimen)

AUCinf is the area under the plasma concentration-time profile from time 0 extrapolated to infinite time. (NCT02718417)
Timeframe: Pre-dose and at 1, 3, 4, 5, 6, 10, and 24 hours post paclitaxel infusion on Day 1 of Cycle 2

Interventionng*hr/mL (Geometric Mean)
PK: Chemotherapy Followed by Avelumab18070
PK: Chemotherapy + Avelumab Followed by Avelumab16190
PK: Chemotherapy Followed by Observation17470

[back to top]

Percentage of Participants With Pathological Complete Response (pCR)

pCR was defined (for neoadjuvant participants who underwent interval debulking surgery [IDS]), as the chemotherapy response score 3 (CSR3), based on a study by Bohm et al, 2015. CSR3 was defined as complete or near-complete response with no residual tumor or minimal irregularly scattered tumor foci seen as individual cells, cell groups, or nodules up to 2 mm. Complete or near-complete response was defined as complete or near-complete microscopic disappearance of invasive tumor/ residual disease. (NCT02718417)
Timeframe: Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Interventionpercentage of participants (Number)
Chemotherapy Followed by Avelumab15.7
Chemotherapy + Avelumab Followed by Avelumab17.4
Chemotherapy Followed by Observation25.9

[back to top]

Progression-Free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR)

BICR assessed PFS: Duration from randomization until disease progression or death. PFS data was censored on the date of the last adequate tumor assessment for participants who did not have an event (progression of disease or death), who started a new anti-cancer therapy prior to an event or for participants with an event after 2 or more missing tumor assessments. Progression as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1: as at least a 20 percent (%) increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of one or more new lesions was also considered progression. Analysis was performed using Kaplan-Meier method. (NCT02718417)
Timeframe: Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Interventionmonths (Median)
Chemotherapy Followed by Avelumab16.8
Chemotherapy + Avelumab Followed by Avelumab18.1
Chemotherapy Followed by ObservationNA

[back to top]

Progression-Free Survival (PFS) as Assessed by Investigator

Investigator assessed PFS was defined as time (in months) from date of randomization to the first documentation of disease progression or death (due to any cause), whichever occurred first. Progression as per RECIST 1.1, was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must have also demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. Analysis was performed using a Cox's Proportional Hazard model stratified by the randomization strata and a stratified log-rank test. (NCT02718417)
Timeframe: Baseline to progression of disease or discontinuation from the study or death, whichever occurred first (maximum duration of 27 months)

Interventionmonths (Median)
Chemotherapy Followed by Avelumab13.8
Chemotherapy + Avelumab Followed by Avelumab16.1
Chemotherapy Followed by Observation15.0

[back to top]

Change From Baseline in Vital Signs - Blood Pressure at Day 1 of Cycles 2, 3, 4 in Chemotherapy Phase; Days 1, 15 and 29 of Cycles 1 and 2 in Maintenance/ Observation Phase and at End of Treatment

Vital signs included blood pressure and pulse rate. Blood pressure included sitting diastolic blood pressure (DBP) and sitting systolic blood pressure (SBP). MP is applicable only for two arms 'Chemotherapy followed by Avelumab' and 'Chemotherapy + Avelumab followed by Avelumab'. OP is applicable only for third arm 'Chemotherapy followed by Observation'. Category titles 'MP/OP' imply which ever phase was applicable for the respective reporting arms. (NCT02718417)
Timeframe: Baseline, first 3 months of Chemotherapy Phase (CP): Day 1 of Cycles 2, 3 and 4 (each cycle 21 days); Maintenance/Observation Phase (MP/OP): Days 1, 15 and 29 of Cycles 1 and 2 (each cycle 42 days) and at end of treatment (up to 27 months)

Interventionmillimeters of mercury (Mean)
CP: Change at Day 1, Cycle 2: Sitting DBPCP: Change at Day 1, Cycle 3: Sitting DBPCP: Change at Day 1, Cycle 4: Sitting DBPMP/OP: Change at Day 1, Cycle 1: Sitting DBPMP/OP: Change at Day 15, Cycle 1: Sitting DBPMP/OP: Change at Day 29, Cycle 1: Sitting DBPMP/OP: Change at Day 1, Cycle 2: Sitting DBPChange at EOT : Sitting DBPCP: Change at Day 1, Cycle 2: Sitting SBPCP: Change at Day 1, Cycle 3: Sitting SBPCP: Change at Day 1, Cycle 4: Sitting SBPMP/OP: Change at Day 1, Cycle 1: Sitting SBPMP/OP: Change at Day 15, Cycle 1: Sitting SBPMP/OP: Change at Day 29, Cycle 1: Sitting SBPMP/OP: Change at Day 1, Cycle 2: Sitting SBPChange at EOT: Sitting SBP
Chemotherapy Followed by Observation0.701.00-0.40-0.90-9.70-8.30-0.700.701.001.700.600.00-4.70-9.30-0.502.90

[back to top]

Pathological Complete Response (PathCR) Rate

Defined as number of patients with pathologic complete responses (pCR) divided by total evaluable patients. pCR is defined as no recognized cancer and margins free of tumor as found by the pathologist following resection of the esophageal specimen and accompanying lymph nodes. (NCT02730546)
Timeframe: Up to 3 years

Interventionpercentage of patients (Number)
Treatment (Pembrolizumab, Chemotherapy, Radiation, Surgery)22.6

[back to top]

Overall Survival (OS) in All Randomized Participants

Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) (NCT02741570)
Timeframe: From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)

InterventionMonths (Median)
Nivolumab + Ipilimumab13.90
EXTREME Regimen13.50

[back to top]

Overall Survival (OS) in All Randomized Participants - Extended Collection

Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) (NCT02741570)
Timeframe: From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)

InterventionMonths (Median)
Nivolumab + Ipilimumab13.90
EXTREME Regimen13.50

[back to top]

Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20 - Extended Collection

Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) (NCT02741570)
Timeframe: From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)

InterventionMonths (Median)
Nivolumab + Ipilimumab17.74
EXTREME Regimen14.59

[back to top]

Duration of Objective Response (DOR)

"The time between the first documented response (Complete response (CR) or partial response (PR)) and progression or death, per RECIST 1.1 by blinded independent central review (BICR) assessment. (Based on Kaplan-Meier Estimates)~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters." (NCT02741570)
Timeframe: From randomization to the first documented response (CR or PR) and progression (up to approximately 65 months)

,
InterventionMonths (Median)
All randomized participantsRandomized PD-L1 CPS >= 20 participants
EXTREME Regimen5.886.97
Nivolumab + Ipilimumab16.5933.51

[back to top]

Objective Response Rate (ORR)

"Objective Response Rate (ORR) is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR). Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria by blinded independent central review (BICR) assessment.~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters." (NCT02741570)
Timeframe: From randomization up to approximately 65 months

,
InterventionPercent (Number)
All randomized participantsRandomized PD-L1 CPS >= 20 participants
EXTREME Regimen37.135.4
Nivolumab + Ipilimumab24.234.1

[back to top]

Progression Free Survival (PFS)

"PFS is defined as the time between the date of randomization and the date of first documented tumor progression, based on Blinded Independent Central Review (BICR) assessments (per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria), or death due to any cause, whichever occurs first. Participants who neither progress nor die will be censored on the date of their last tumor assessment. Participants who receive subsequent anti-cancer therapy prior to documented progression, will be censored on the date of their last tumor assessment prior to subsequent therapy. (Based on Kaplan-Meier Estimates)~Progression is defined as at least a 20% increase in the sum of diameters of target lesions, in addition the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)." (NCT02741570)
Timeframe: From randomization to disease progression or death (Up to approximately 65 months)

,
InterventionMonths (Median)
Randomized participantsRandomized PD-L1 CPS >= 20 participants
EXTREME Regimen6.776.97
Nivolumab + Ipilimumab3.295.39

[back to top]

Overall Survival (OS) in Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥20

Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) (NCT02741570)
Timeframe: From randomization to date of death or date the participant was last known to be alive (Up to approximately 55 months)

InterventionMonths (Median)
Nivolumab + Ipilimumab17.58
EXTREME Regimen14.59

[back to top]

Overall Survival (OS) in Randomized Participants With Programmed Death-Ligand 1 (PD-L1) With a Combined Positive Score (CPS) ≥ 1

Overall survival (OS) is defined as the time between randomization and death. For participants without documentation of death, OS will be censored on the last date the participant was known to be alive. Overall survival will be censored at the date of randomization for participants who were randomized but had no follow-up. Survival follow-up will be conducted every 3 months after participants off-treatment date. (Based on Kaplan-Meier estimates) (NCT02741570)
Timeframe: From randomization to date of death or date the participant was last known to be alive (Up to approximately 65 months)

InterventionMonths (Median)
Nivolumab + Ipilimumab15.67
EXTREME Regimen13.24

[back to top]

Objective Response Rate (ORR) as Measured by RECIST 1.1 at Month 24

"ORR is the number of patients whose best tumor response outcome by Month 24 is a Complete Response (CR) or Partial Response (PR), divided by the total number of evaluable patients.~Per the Response Evaluation Criteria in Solid Tumors (RECIST v1.1.):~CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD" (NCT02744898)
Timeframe: Up to Month 24

InterventionPercentage of participants (Number)
Carboplatin AUC and Abraxane 100mg/m233.3

[back to top]

Progression-Free Survival (PFS) at Month 24

PFS is defined as the time from first dosing to the first observation of disease progression or death due to any cause. PFS was estimated beyond the collected data using Kaplan Meier methods. (NCT02744898)
Timeframe: Up to Month 24

InterventionMonths (Median)
Carboplatin AUC and Abraxane 100mg/m228.2

[back to top]

Tolerability Measured Completion of Dose Regimen

Tolerability for an individual patient will be defined as remaining on the study for 6 cycles with two or fewer dose reductions. (NCT02744898)
Timeframe: 24 months

InterventionParticipants (Count of Participants)
Carboplatin AUC and Abraxane 100mg/m216

[back to top]

Progression Free Survival (PFS) With Carboplatin, Etoposide and MPDL3280A Compared to Chemotherapy Alone According to RECIST v1.1

Disease progression will be assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT and bone scans. (NCT02748889)
Timeframe: From the first occurrence of progression or death, whichever occurred first, assessed up to 2 years.

Interventionmonths (Mean)
Carboplatin, Etoposide and MPDL3280A6

[back to top]

Relative Dose Intensity as Measured by Mean Percent of Intended Cycles Completed

Prospective evaluation of the Relative Dose Intensity (RDI) of weight-based dose dense weekly paclitaxel and carboplatin as measured by the average percent of completed treatment cycles out of the intended therapeutic plan (NCT02756013)
Timeframe: Up to 190 days

Interventionpercent of intended cycles completed (Mean)
Paclitaxel + Carboplatin77.5

[back to top]

Number of Participants With Progression-free Survival (PFS)

Progression will be evaluated in this study using the new international criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT02756013)
Timeframe: every 3 months for up to 2 years, then every 6 months (up to 31 months)

InterventionParticipants (Count of Participants)
3 months6 months9 months12 months15 months18 months21 months24 months31 months
Paclitaxel + Carboplatin332222222

[back to top]

Plasma Concentration of Carboplatin in the Global Population

Plasma concentration of carboplatin in the Global population. (NCT02763579)
Timeframe: Predose, before end of infusion, and after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

,
Interventionng/mL (Mean)
Pre-Dose on Day 1 of Cycle 1Before End of Infusion on Day 1 of Cycle 1Post Infusion on Day 1 of Cycle 1Pre-Dose on Day 1 of Cycle 3Before End of Infusion on Day 1 of Cycle 3Post Infusion on Day 1 of Cycle 3
Atezolizumab + Carboplatin + EtoposideNA112006860126113006540
Placebo + Carboplatin + EtoposideNA133007200144139007180

[back to top]

Percentage of Participants With at Least One Adverse Event in the Global Population

The percentage of participants with at least one adverse event in the global population. (NCT02763579)
Timeframe: Baseline until up to 90 days after end of treatment (up to approximately 49 months)

InterventionPercentage of participants (Number)
Placebo + Carboplatin + Etoposide96.4
Atezolizumab + Carboplatin + Etoposide100.0

[back to top]

PFS Rate at 6 Months and at 1 Year in Global Population

PFS rates at 6 months and at 1 year is defined as the proportion of participants who are alive without disease progression 6 months and 1 year after randomization, respectively. (NCT02763579)
Timeframe: 6 months, 1 year

,
InterventionPercentage of participants (Number)
6 Months1 Year
Atezolizumab + Carboplatin + Etoposide30.8612.62
Placebo + Carboplatin + Etoposide22.395.35

[back to top]

Maximum Observed Serum Concentration (Cmax) of Atezolizumab in the Global Population

Atezolizumab maximum observed plasma concentration (Cmax; 30 minutes following the end of the atezolizumab infusion) for each respective day. (NCT02763579)
Timeframe: Post-dose Day 1 of Cycle 1 (cycle length = 21 days)

Interventionμg/mL (Mean)
Atezolizumab + Carboplatin + Etoposide389

[back to top]

Duration of Response (DOR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator using RECIST v1.1 or death from any cause, whichever comes first. (NCT02763579)
Timeframe: First occurrence of PR or CR until PD or death, whichever occurs first (up to approximately 23 months)

InterventionMonths (Median)
Placebo + Carboplatin + Etoposide3.1
Atezolizumab + Carboplatin + Etoposide4.1

[back to top]

Duration of Progression-Free Survival (PFS) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least 20% increase in the sum of the longest diameter of target lesions compared to baseline, or unequivocal progression in non-target lesion(s), or the appearance of new lesion(s). (NCT02763579)
Timeframe: Baseline until PD or death, whichever occurs first (up to approximately 23 months)

InterventionMonths (Median)
Placebo + Carboplatin + Etoposide4.3
Atezolizumab + Carboplatin + Etoposide5.2

[back to top]

Minimum Observed Serum Concentration (Cmin) of Atezolizumab in the Global Population

Atezolizumab pre-dose plasma concentration (Cmin) for each respective day. (NCT02763579)
Timeframe: Predose on Day 1 of Cycles 1, 3, 4, 8, 16 and 24 (cycle length = 21 days)

Interventionμg/mL (Mean)
Cycle 1 Day 1Cycle 3 Day1Cycle 4 Day 1Cycle 8 Day 1Cycle 16 Day 1Cycle 24 Day 1
Atezolizumab + Carboplatin + EtoposideNA80.6138186196221

[back to top]

Time to Deterioration (TTD) Per European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) Core 30 (C30) and Supplemental Lung Cancer Module (QLQ-LC13) in the Global Population

"TTD according to the EORTC QLQ-C30 and EORTC QLQ-LC13 measures were evaluated in each of the following linearly transformed symptom scores: cough, dyspnea (single item), dyspnea (multi-item subscale), chest pain, or arm/shoulder pain. The linear transformation gives each individual symptom subscale a possible score of 0 to 100. For the symptom to be considered deteriorated, a score increase of ≥10 points above baseline must be held for at least two consecutive assessments or an initial score increase of ≥10 points is followed by death within 3 weeks from the last assessment. A ≥ 10-point change in the symptoms subscale score is perceived by participants as clinically significant." (NCT02763579)
Timeframe: Baseline until deterioration per symptom subscale (up to approximately 23 months)

,
InterventionMonth (Median)
CoughPain in ChestPain in Arm or ShoulderDyspnea
Atezolizumab + Carboplatin + Etoposide20.3NANANA
Placebo + Carboplatin + EtoposideNANANA5.6

[back to top]

Percentage of Participants With Anti-Drug Antibodies (ADA) to Atezolizumab in the Global Population

The baseline prevalence and post-baseline incidence of ADAs against atezolizumab. (NCT02763579)
Timeframe: Predose (0 hours [H]) on Day (D) 1 of Cycles (C) 1, 2, 3, 4, 8, 16, and every 8 cycles (Q8C) thereafter (cycle = 21 days) until treatment discontinuation (up to 23 months) and 120 days after last dose (up to approximately 23 months overall)

InterventionPercentage of participants (Number)
Baseline evaluable participantsPost-baseline evaluable participants
Atezolizumab + Carboplatin + Etoposide2.018.6

[back to top]

OS Rate at 1 Year and 2 Years in the Global Population

OS rates at 1 and 2 years is defined as the proportion of participants who are alive 1 year and 2 years after randomization, respectively. (NCT02763579)
Timeframe: 1 year, 2 years

,
InterventionPercentage of participants (Number)
1 Year2 Years
Atezolizumab + Carboplatin + Etoposide51.69NA
Placebo + Carboplatin + Etoposide38.23NA

[back to top]

Plasma Concentration of Etoposide in the Global Population

Plasma concentration of etoposide in the Global Population. (NCT02763579)
Timeframe: Predose, before end of infusion, 1 and 4 hours after end of carboplatin infusion on Day 1 of Cycle 1 and Cycle 3 (cycle = 21 days)

,
Interventionng/mL (Mean)
Pre-Dose on Day 1 of Cycle 1Before End of Infusion on Day 1 of Cycle 11 Hour Post Infusion on Day 1 of Cycle 14 Hours Post Infusion on Day 1 of Cycle 1Pre-Dose on Day 1 of Cycle 3Before End of Infusion on Day 1 of Cycle 31 Hour Post Infusion on Day 1 of Cycle 34 Hours Post Infusion on Day 1 of Cycle 3
Atezolizumab + Carboplatin + EtoposideNA19400126007300NA17700122007960
Placebo + Carboplatin + EtoposideNA17000111007640NA16600124006740

[back to top]

Percentage of Participants With Objective Response Rate (ORR) as Assessed by the Investigator Using RECIST v1.1 in the Global Population

Objective response (OR) is defined as complete response (CR) or partial response (PR) as determined by the investigator according to RECIST v1.1. (NCT02763579)
Timeframe: Baseline until partial response (PR) or complete response (CR), whichever occurs first (up to approximately 23 months)

InterventionPercentage of participants (Number)
Placebo + Carboplatin + Etoposide76.7
Atezolizumab + Carboplatin + Etoposide74.1

[back to top]

Duration of Overall Survival (OS) in the Global Population

OS is defined as the time from randomization to death from any cause. (NCT02763579)
Timeframe: Baseline until death from any cause (up to approximately 23 months)

InterventionMonths (Median)
Placebo + Carboplatin + Etoposide10.3
Atezolizumab + Carboplatin + Etoposide12.3

[back to top]

Monitor Quality of Life During Combination Therapy and Single Agent Maintenance Therapy With Anti-PD-1 Therapy With the Functional Assessment of Cancer Therapy- Ovarian (FACT- O) Surveys at Intervals During Therapy.

"Each cycle is 21 days. All participants were asked to complete FACT-O surveys at baseline/ time of enrollment, at 3 months, 6 months and 18 months from initiation of therapy.~FACT-O is a validated 26-item summary score 112 points that captures the FACT-General (FACT-G) QOL dimensions of Physical Well-Being (7 items), Functional Well-Being (7 items), and an Ovarian Cancer Subscale (12 items). FACT-0 is a survey with 39 items self administered survey. Each item is scored on 5 point Likert-type scale. The FACT-0 scoring range is from 0-44. The subscale scoring ranges for FACT-G is 0-108. The higher the total score the better the patient well-being. the outcome measure data represent FACT-G scoring as it is the section that pertains to QOL.~https://www.facit.org/measures/FACT-O" (NCT02766582)
Timeframe: Time of enrollment until 18 months from initiation of therapy

Interventionscore on a scale (Median)
screening3 months6 months18 months
Chemotherapy Combined With Pembrolizumab858883.986

[back to top]

Progression Free Survival (PFS) of Combination Platinum Based Therapy With Anti-Programmed Death (PD)-1 Therapy Followed by Maintenance Anti-PD-1 Therapy in Patients With Epithelial Ovarian Cancer (EOC).

"Time to progression free survival (PFS) is the period from study entry (first dose of therapy) until disease progression, death or date of last contact.~All patients underwent baseline computed tomographic scans prior to initiation of therapy. The residual disease information was collected from surgical operative reports as well as post operative CT scans. Treatment responses were assessed with CA 125 at each cycle of therapy. CT scans were performed post-operatively prior to initiation of systemic therapy, at the completion of combination platinum, taxane, and pembrolizumab therapy, and at the completion of maintenance pembrolizumab therapy. CT scans were also performed with increasing CA 125 or if clinically indicated per treating physician and assessments were made using response evaluation criteria in solid tumor (RECIST) criteria defined as a 20% increase in the sum of the longest diameter of target lesions, or measurable increase in non-target l" (NCT02766582)
Timeframe: measured from date of completion of primary therapy to the date of the first clinical, biochemical or radiologic evidence of disease progression or death due to any cause

Interventionmonths (Median)
Chemotherapy Combined With Pembrolizumab13.2

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented. (NCT02775435)
Timeframe: Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

InterventionParticipants (Count of Participants)
Pembrolizumab + Chemotherapy273
Chemotherapy274

[back to top]

Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death. DOR as assessed by blinded independent central review per RECIST 1.1 is presented. (NCT02775435)
Timeframe: Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy7.7
Chemotherapy4.8

[back to top]

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 is presented. (NCT02775435)
Timeframe: Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy6.4
Chemotherapy4.8

[back to top]

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. OS is presented. (NCT02775435)
Timeframe: Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy15.9
Chemotherapy11.3

[back to top]

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

The number of participants who discontinued study treatment due to an AE is presented. (NCT02775435)
Timeframe: Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

InterventionParticipants (Count of Participants)
Pembrolizumab + Chemotherapy65
Chemotherapy33

[back to top]

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1. ORR as assessed by blinded independent central review per RECIST 1.1 is presented. (NCT02775435)
Timeframe: Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy57.9
Chemotherapy38.4

[back to top]

Median Change in Quality of Life (QOL) From Baseline to 12 Months Post Treatment

"Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 12 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs.~Range for Questionnaires:~HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148" (NCT02784288)
Timeframe: Baseline to 12 Months post-treatment (up to approximately 15 months post neck dissection).

Interventionscore on a scale (Median)
HN-QOL: EatingHN-QOL: SpeechHN-QOL: PainHN-QOL: EmotionUW-QOL: Pain_generalUW-QOL: Pain_mouthUW-QOL: Pain_throatUW-QOL: DisfigurementUW-QOL: ActivityUW-QOL: RecreationUW-QOL: EmploymentUW-QOL: ChewingUW-QOL: SwallowingUW-QOL: Saliva amountUW-QOL: Saliva consistencyUW-QOL: TasteUW-QOL: SpeechUW-QOL: Mucus amountUW-QOL: Mucus consistencyV-RQOL: PhysicalV-RQOL: EmotionalV-RQOL: TotalFACT H&N: Physical Well BeingFACT H&N: Social Well BeingFACT H&N: Emotional Well BeingFACT H&N: Functional Well BeingFACT H&N: HN subscaleFACT H&N: Total
Neck Dissection-4.206.310.700-10000000100100000001030-14

[back to top]

Median Change in Quality of Life (QOL) From Baseline to 24 Months Post Treatment

"Four QOL instruments will be administered: the University of Washington Quality of Life (UWQOL), University of Michigan Head and Neck Quality of Life Instrument (HN-QOL), the University of Michigan Voice Related Quality of Life Measure (V-RQOL), and the FACT Head and Neck (version 4) (FACT H&N). Results of each of the 4 surveys will be reported in separate rows in the results table. The difference in scores from baseline to 24 months after completion of study treatment is calculated for each participant, with the median across all participants reported for each survey. Higher scores indicate better QOLs.~Range for Questionnaires:~HN QOLs: -100 to +100 VR QOLs: -100 to +100 UW QOLs: -100 to +100 FACTHN Physical: -28 to +28 FACTHN Social: -28 to +28 FACTHN Emotional: -24 to +24 FACTHN Functional: -28 to +28 FACTHN subscale: -40 to +40 FACTHN Total: -148 to +148" (NCT02784288)
Timeframe: 2 years post-treatment (up to approximately 27 months post neck dissection)

Interventionscore on a scale (Median)
HN-QOL- EatingHN-QOL- SpeechHN-QOL- PainHN-QOL- EmotionUWQOL-Pain_GeneralUWQOL- Pain_MouthUWQOL- Pain_throatUWQOL- DisfigurementUWQOL- activityUWQOL-RecreationUWQOL- EmploymentUWQOL- ChewingUWQOL- SwallowingUWQOL- Saliva amountUWQOL- Saliva consistencyUWQOL- TasteUWQOL- SpeechUWQOL- Mucus amountUWQOL- Mucus consistencyV-RQOL- PhysicalV-RQOL- EmotionalV-RQOL- TotalFACT H&N- Physical well beingFACT H&N- Social well beingFACT H&N- Emotional well beingFACT H&N- Functional well beingFACT H&N- HN subscaleFACT H&N- total FACTHN
Neck Dissection0.00.06.310.7-100-100000001000000000002021

[back to top]

Progression Free Survival (PFS)

Proportion of patients alive and free of disease persistence, progression or recurrence at 3 years from the date of completion of study treatment. Persistent disease at completion of treatment, post-treatment recurrence or disease specific death will be defined events for progression free survival (PFS). (NCT02784288)
Timeframe: 3 Years

Interventionpercentage of participants (Number)
Neck Dissection97

[back to top]

Disease Specific Survival (DSS)

Proportion of patients alive at 3 years from date of neck dissection. Death from OPSCC (Oropharyngeal Squamous Cell Cancer) will be considered an event for DSS. Death from other causes will be censored at time of death. (NCT02784288)
Timeframe: 3 Years

Interventionpercentage of participants (Number)
Neck Dissection100

[back to top]

Impact of Neck Dissection on Shoulder Function Using the Neck Dissection Impairment Index

"The neck dissection impairment index will be scored and summarized for all patients who receive neck dissection.~Scores ranging from 0-100 with higher scores indicating better function" (NCT02784288)
Timeframe: 2 years post-treatment (up to approximately 27 months post neck dissection)

Interventionscore on a scale (Median)
Neck Dissection98

[back to top]

Overall Survival (OS)

Proportion of patients alive at 3 years from date of neck dissection. Death from any cause will be considered an event for overall survival. (NCT02784288)
Timeframe: 3 Years

InterventionPercent of Patients (Number)
Neck Dissection100

[back to top]

Percent of Patients Who Achieve a pCR

pCR is pathologic complete response defined as ypT0/isN0 on pathology report (NCT02789657)
Timeframe: at surgery post approximately 18 weeks of treatment

InterventionParticipants (Count of Participants)
Experimental: Optimal- 18 Weeks19
Experimental: Sub-optimal With AC2
Experimental: Optimal With AC0
Experimental: Sub-optimal no AC0

[back to top]

Number of of Patients Who Develop Major Toxicities as Defined in Protocol.

"Defined based on CTCAE version 4:~Neutropenia (grade>2)~Thrombocytopenia (grade >2)~Anemia (grade >2)~Diarrhea (any grade, grade >3)~Neuropathy (any grade, grade 2, grade >3)~Vomiting (any grade, grade >3)" (NCT02789657)
Timeframe: From start of neo-adjuvant treatment through approximately 18 weeks.

,,
InterventionParticipants (Count of Participants)
ANCThrombocytopeniaAnemiaDiarrheaNeuropathyVomiting
Experimental: Optimal- 18 Weeks192202355
Experimental: Sub-optimal no AC202200
Experimental: Sub-optimal With AC323301

[back to top]

Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm

Time to deterioration in global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm. (NCT02807636)
Timeframe: Up to approximately 73 months

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin12.06
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin32.07

[back to top]

PFS Event Free Rate

Progression Free Survival (PFS) Event Free Rate at Year 1 (NCT02807636)
Timeframe: Year 1

InterventionPercentage (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin22.17
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin30.47

[back to top]

Overall Survival (OS) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

OS is defined as the time from randomization to death due to any cause. (NCT02807636)
Timeframe: Baseline until death due to any cause (up to approximately 73 months)

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin13.44
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin16.13

[back to top]

Overall Survival (OS) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

OS is defined as the time from randomization to death due to any cause. (NCT02807636)
Timeframe: Baseline until death due to any cause (up to approximately 73 months)

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin13.34
Atezolizumab Monotherapy15.21

[back to top]

OS Event Free Rate in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Overall Survival (OS) Event Free Rate at 1 Year. (NCT02807636)
Timeframe: Year 1

InterventionPercentage (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin54.56
Atezolizumab Monotherapy57.91

[back to top]

OS Event Free Rate Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Overall Survival (OS) Event Free Rate at 1 Year. (NCT02807636)
Timeframe: Year 1

InterventionPercentage (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin55.00
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin60.00

[back to top]

Objective Response Rate (ORR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Objective response rate (ORR) is defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), observed on two assessments >= 28 days apart per RECIST v1.1, based on investigator assessment. The analysis population for ORR will be all randomized participants with measurable disease at baseline. (NCT02807636)
Timeframe: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)

InterventionPercentage of Participants (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin44.8
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin48.1

[back to top]

Objective Response Rate (ORR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Objective response rate (ORR) is defined as the proportion of participants with a confirmed objective response, either complete response (CR) or partial response (PR), observed on two assessments >= 28 days apart per RECIST v1.1, based on investigator assessment. The analysis population for ORR will be all randomized participants with measurable disease at baseline. (NCT02807636)
Timeframe: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)

InterventionPercentage of Participants (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin44.4
Atezolizumab Monotherapy24.2

[back to top]

Percentage of Participants With Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs)

Percentage of participants with Anti-Therapeutic (Anti-Atezolizumab) Antibodies (ATAs). (NCT02807636)
Timeframe: Up to approximately 35 months

,
InterventionPercentage of participants (Number)
Baseline evaluable participantsPost-baseline evaluable participants
Atezolizumab Monotherapy0.926.3
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin1.219.7

[back to top]

Minimum Atezolizumab Serum Concentration

Minimum atezolizumab serum concentration. (NCT02807636)
Timeframe: Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 8 Day 1, Cycle 16 Day 1, Cycle 24 Day 1, Cycle 32 Day 1, Day 120 post dose of last blinded atezolizumab treatment, and study drug early discontinuation

,
Interventionμg/ mL (Mean)
Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 8 Day 1Cycle 16 Day 1Cycle 24 Day 1Cycle 32 Day 1Day 120 Post Dose of Last Blinded Atezo TrtStudy Drug Early Discontinuation
Atezolizumab Monotherapy80.21291571932202332589.53124
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin79.812215321623524425918.8154

[back to top]

Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm

Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab Monotherapy Arm. (NCT02807636)
Timeframe: Up to approximately 73 months

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin16.10
Atezolizumab Monotherapy9.23

[back to top]

Time to Deterioration in Physical Function as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm

Median time to deterioration in physical function as measured by the QLQ-C30 in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm. (NCT02807636)
Timeframe: Up to approximately 73 months

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin15.74
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin16.39

[back to top]

Time to Deterioration in Global Health Status as Measured by the EORTC QLQ-C30 Score in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab Monotherapy Arm

Time to deterioration in global health status as measured by the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 in the Placebo+Chemo Arm versus Atezolizumab Monotherapy Arm. (NCT02807636)
Timeframe: Up to approximately 73 months

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin12.02
Atezolizumab Monotherapy23.20

[back to top]

Maximum Atezolizumab Serum Concentration

Maximum atezolizumab serum concentration. (NCT02807636)
Timeframe: Cycle 1 Day 1

Interventionμg/ mL (Mean)
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin379
Atezolizumab Monotherapy390

[back to top]

IRF-PFS

Independent review facility PFS (IRF-PFS) is defined as the time from randomization to the first documented disease progression as determined by blinded independent central review with use of RECIST v1.1, or death due to any cause, whichever occurs first. (NCT02807636)
Timeframe: Randomization to first documented disease progression or death from any cause (up to 35 months)

InterventionMonths (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin6.34
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin7.10

[back to top]

Investigator-Assessed Progression-Free Survival (INV-PFS) in Participants Treated With Atezolizumab Monotherapy Arm Compared With Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever occurs first. (NCT02807636)
Timeframe: Baseline up to disease progression, death, or loss of follow-up, whichever occurs first (assessed at baseline, every 9 weeks for 54 weeks and every 12 weeks thereafter up to 35 months)

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin6.31
Atezolizumab Monotherapy2.69

[back to top]

Investigator Assessed Progression-Free Survival (PFS) in the Placebo+Gemcitabine+Carboplatin/Cisplatin Arm Versus Atezolizumab +Gemcitabine+Carboplatin/Cisplatin Arm

PFS is defined as the time from randomization to the first documented disease progression as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever occurs first. (NCT02807636)
Timeframe: Baseline up to first documented disease progression or death, whichever occurs first (up to approximately 35 months)

InterventionMonths (Median)
Placebo+Gemcitabine+Carboplatin/Cisplatin6.34
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin8.18

[back to top]

Duration of Response (DOR) in Atezolizumab+Gemcitabine+Carboplatin/Cisplatin Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Duration of response (DOR) is defined for participants with an objective response as the time from the first documented objective response to documented disease progression per RECIST v1.1, based on investigator assessment, or death due to any cause, whichever occurs first. (NCT02807636)
Timeframe: From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)

InterventionMonths (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin8.15
Atezolizumab+Gemcitabine+Carboplatin/Cisplatin9.13

[back to top]

Duration of Response (DOR) in Atezolizumab Monotherapy Arm Versus Placebo+Gemcitabine+Carboplatin/Cisplatin Arm

Duration of response (DOR) is defined for participants with an objective response as the time from the first documented objective response to documented disease progression per RECIST v1.1, based on investigator assessment, or death due to any cause, whichever occurs first. (NCT02807636)
Timeframe: From first documented objective response (CR or PR) to disease progression, death, or loss of follow-up, whichever occurs first (up to approximately 73 months)

InterventionMonths (Number)
Placebo+Gemcitabine+Carboplatin/Cisplatin8.11
Atezolizumab Monotherapy29.63

[back to top]

Overall Survival (OS)

The event of interest was defined as death from any cause. OS was defined as the interval from date of randomization until the date of death due to any cause. OS was summarized using Kaplan-Meier estimates of the quartiles for each treatment arm, and 95% CIs for the medians were calculated. (NCT02810457)
Timeframe: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.

InterventionMonths (Median)
FKB238 / Paclitaxel / Carboplatin14.13
Avastin / Paclitaxel / Carboplatin16.95

[back to top]

Duration Of Response (DOR)

DOR was evaluated in this study as a secondary efficacy endpoint. Only the patients defined as responders in the primary analysis of ORR were taken into account for the analysis of DOR. The event of interest was defined as first documented disease progression or death due to any reason, whichever occurred first. DOR was defined as the interval from the first documented response (as defined per RECIST v1.1) until the earlier date of the first documented disease progression or death due to any reason. The date of first documented response was taken as the date of the first tumor assessment with an overall visit response of CR or PR. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. DOR was calculated in units of months. (NCT02810457)
Timeframe: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.

Interventionmonths (Median)
FKB238 / Paclitaxel / Carboplatin6.47
Avastin / Paclitaxel / Carboplatin6.31

[back to top]

Serum Trough Concentration (Ctrough)

Ctrough (pre-infusion) and serum maximum concentration (Cmax; at completion of infusion) were compared between treatment arms and time points, and descriptive statistics provided. Ctrough and Cmax concentrations were summarized using the pharmacokinetics (PK) population for each visit at which samples were taken. The pre-dose serum concentrations at Cycles 2, 4, and 6 were considered as Ctrough values and the post-dose serum concentrations at Cycles 1 and 4 were considered as Cmax values. PK data at Cycle 1 Day 1 pre-infusion were not calculable and are therefore not presented in the outcome measure data table. Data are only provided for the time points at which the serum trough concentration was measured. (NCT02810457)
Timeframe: Cycle 1 Day 1 (pre- and post-infusion), Cycle 2 Day 1 (pre), Cycle 4 Day 1 (pre and post), Cycle 6 Day 1 (pre), discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up.

,
Interventionug/ml (Geometric Mean)
Cycle 1, Day 1 end of infusionCycle 2, Day 1 pre-infusionCycle 4, Day 1 pre-infusionCycle 4, Day 1 end of infusionCycle 6, Day 1 pre-infusion
Avastin / Paclitaxel / Carboplatin245.1148.4883.26373.92108.22
FKB238 / Paclitaxel / Carboplatin255.1542.7477.16339.9187.25

[back to top]

Proportion of Patients Developing Anti-drug Antibodies (ADAs)

The ADA levels were summarized at baseline and post-baseline time points using descriptive statistics. (NCT02810457)
Timeframe: Pre-dose at Cycles 1, 2, 4 and 6, discontinuation visit, and every 12 weeks (up to 1 year [±14 days] after randomisation) until death, or the patient was lost to follow-up, whichever occurred first.

,
Interventionpercentage of participants (Number)
ADA prevalence (ADA positive, baseline or post)Treatment-emergent ADA positive (ADA incidence)
Avastin / Paclitaxel / Carboplatin3.02.3
FKB238 / Paclitaxel / Carboplatin3.02.3

[back to top]

ORR at Week 19

ORR (by RECIST v1.1) at Week 19 was defined as the proportion of patients with a BOR of CR or PR assessed at Week 19. Only tumor assessments performed up until 19 weeks (i.e. Week 18 assessment + 7 day assessment window) from randomization were considered in this analysis. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. Overall Response=CR+PR. (NCT02810457)
Timeframe: From the date of randomization up to Week 19.

Interventionpercentage of participants (Number)
FKB238 / Paclitaxel / Carboplatin47.8
Avastin / Paclitaxel / Carboplatin51.0

[back to top]

Overall Response Rate (ORR) Assessed as the Proportion of Patients With a Best Overall Response (BOR) of Either Complete Response (CR) or Partial Response (PR)

The primary variable in this study was ORR, defined as the proportion of patients with a BOR of CR or PR (by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)). A BOR was defined as the best response (in the order of CR, PR, stable disease (SD), no evidence of disease (NED), progressive disease (PD), and not evaluable (NE)) among all post-baseline disease assessments that occurred until progression, or last evaluable assessment in the absence of progression prior to the initiation of subsequent anti-cancer therapy, irrespective of whether or not patients discontinued the study treatment. The 95% Pearson-Clopper confidence interval (CI) of ORR for each treatment arm was provided. Per RECIST v1.1 for target lesions and assessed by computed tomography (CT) or, if contraindicated, magnetic resonance imaging (MRI): CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions. Overall Response=CR+PR. (NCT02810457)
Timeframe: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.

Interventionpercentage of participants (Number)
FKB238 / Paclitaxel / Carboplatin51.6
Avastin / Paclitaxel / Carboplatin53.7

[back to top]

Progression-free Survival (PFS)

The event of interest for PFS was defined as the interval from the date of randomization until first documented disease progression or death from any cause, whichever occurs first. Disease progression was based on tumor assessments according to RECIST v1.1 criteria. The items of the overall response CR, PR, SD and NED were taken as progression-free whereas PD denoted disease progression. PFS was summarized using Kaplan-Meier estimates of the quartiles for each treatment arm, and 95% CIs for the medians were calculated. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: PD=at least a 20% increase in the sum of the longest diameter of target lesions, unequivocal progression of existing non-target lesions, or the appearance of one or more new lesions. (NCT02810457)
Timeframe: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.

InterventionMonths (Median)
FKB238 / Paclitaxel / Carboplatin7.72
Avastin / Paclitaxel / Carboplatin7.62

[back to top]

Disease Control Rate (DCR) Assessed as the Proportion of Patients With a BOR of Either CR, PR, SD or NED

The DCR was defined as the proportion of patients defined as responders. The number and percentage of responders and non-responders and the 95% Pearson-Clopper CI of DCR for each treatment arm was provided. The odds ratio for treatment (FKB238 arm versus Avastin arm) and the corresponding 95% Wald CI were produced based on a logistic regression analysis of DCR. Per RECIST v1.1 for target lesions and assessed by CT or, if contraindicated, MRI: CR=disappearance of all target lesions; PR=at least 30% decrease from baseline in the sum of diameters of target lesions; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study. DCR=CR+PR+SD (≥ 6 weeks). (NCT02810457)
Timeframe: Until data cut-off, which occurred 12 months after randomization of the last patient enrolled, for a total estimated period of time of up to approximately 30 months.

Interventionpercentage of participants with response (Number)
FKB238 / Paclitaxel / Carboplatin87.6
Avastin / Paclitaxel / Carboplatin87.5

[back to top]

Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors

Objective response rate is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy44.9
Part 2: Placebo + Chemotherapy38.9

[back to top]

Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors

Objective response rate is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy52.7
Part 2: Placebo + Chemotherapy40.8

[back to top]

Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors

Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + Chemotherapy17.6
Part 2: Placebo + Chemotherapy16.0

[back to top]

Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors

Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + Chemotherapy23.0
Part 2: Placebo + Chemotherapy16.1

[back to top]

Part 2: Overall Survival (OS) - All Participants

Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + Chemotherapy17.2
Part 2: Placebo + Chemotherapy15.5

[back to top]

Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. (NCT02819518)
Timeframe: Up to approximately 52 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy20.5
Part 2: Placebo + Chemotherapy13.5

[back to top]

Part 2: Percentage of Participants Who Experienced an AE- All Participants

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy98.6
Part 2: Placebo + Chemotherapy98.2

[back to top]

Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors

Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + Chemotherapy9.7
Part 2: Placebo + Chemotherapy5.6

[back to top]

Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors

Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by BICR or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + Chemotherapy7.6
Part 2: Placebo + Chemotherapy5.6

[back to top]

Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors

"The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented." (NCT02819518)
Timeframe: Baseline and Week 15

InterventionScores on a scale (Least Squares Mean)
Part 2: Pembrolizumab + Chemotherapy-3.92
Part 2: Placebo + Chemotherapy-3.15

[back to top]

Part 2: Progression-Free Survival (PFS) - All Participants

Progression-free survival was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on assessments by blinded independent central review (BICR) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + Chemotherapy7.5
Part 2: Placebo + Chemotherapy5.6

[back to top]

Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. (NCT02819518)
Timeframe: Up to approximately 39 months

InterventionPercentage of Participants (Number)
Part 1: Pembrolizumab + Nab-paclitaxel38.5
Part 1: Pembrolizumab + Paclitaxel50.0
Part 1: Pembrolizumab + Gemcitabine/Carboplatin27.3

[back to top]

Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants

An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. (NCT02819518)
Timeframe: Up to approximately 39 months

InterventionPercentage of Participants (Number)
Part 1: Pembrolizumab + Nab-paclitaxel100.0
Part 1: Pembrolizumab + Paclitaxel100.0
Part 1: Pembrolizumab + Gemcitabine/Carboplatin100.0

[back to top]

Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors

"The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented." (NCT02819518)
Timeframe: Baseline and Week 15

InterventionScores on a scale (Least Squares Mean)
Part 2: Pembrolizumab + Chemotherapy-2.69
Part 2: Placebo + Chemotherapy-0.88

[back to top]

Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants

"The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented." (NCT02819518)
Timeframe: Baseline and Week 15

InterventionScores on a scale (Least Squares Mean)
Part 2: Pembrolizumab + Chemotherapy-3.52
Part 2: Placebo + Chemotherapy-2.15

[back to top]

Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented. (NCT02819518)
Timeframe: Baseline and Week 15

InterventionScores on a scale (Least Squares Mean)
Part 2: Pembrolizumab + Chemotherapy12.50
Part 2: Placebo + Chemotherapy12.36

[back to top]

Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented. (NCT02819518)
Timeframe: Baseline and Week 15

InterventionScores on a scale (Least Squares Mean)
Part 2: Pembrolizumab + Chemotherapy13.00
Part 2: Placebo + Chemotherapy11.86

[back to top]

Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors

EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented. (NCT02819518)
Timeframe: Baseline and Week 15

InterventionScores on a scale (Least Squares Mean)
Part 2: Pembrolizumab + Chemotherapy13.56
Part 2: Placebo + Chemotherapy13.26

[back to top]

Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors

Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy58.6
Part 2: Placebo + Chemotherapy53.6

[back to top]

Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors

Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy65.0
Part 2: Placebo + Chemotherapy54.4

[back to top]

Part 2: Disease Control Rate (DCR) - All Participants

Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy56.0
Part 2: Placebo + Chemotherapy51.2

[back to top]

Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors

For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + ChemotherapyNA
Part 2: Placebo + Chemotherapy6.8

[back to top]

Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors

For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + ChemotherapyNA
Part 2: Placebo + Chemotherapy7.3

[back to top]

Part 2: Duration of Response (DOR) - All Participants

For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionMonths (Median)
Part 2: Pembrolizumab + ChemotherapyNA
Part 2: Placebo + Chemotherapy6.5

[back to top]

Part 2: Objective Response Rate (ORR) - All Participants

Objective response rate is defined as the percentage of participants in the analysis population who have a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented. (NCT02819518)
Timeframe: Up to approximately 53 months

InterventionPercentage of Participants (Number)
Part 2: Pembrolizumab + Chemotherapy40.8
Part 2: Placebo + Chemotherapy37.0

[back to top]

Pathologic Objective Response Rate (pORR) in Participants Receiving Protocol Therapy

The pORR will be calculated as the percentage of participants with pathologic complete response (pCR) and pathologic partial response (pPR) overall as best response. For this protocol, pathologic complete response (pCR) will be defined as no residual macroscopic or (viable) microscopic disease. Pathologic partial response (pPR) will be defined as the presence of residual (viable) microscopic tumor, and the size of the largest focus will be provided for possible outcome correlation. (NCT02834975)
Timeframe: Up to 48 months

Interventionpercentage of participants (Number)
Pembrolizumab, Paclitaxel + Carboplatin60

[back to top] [back to top]

Progression-Free Survival (PFS)

Progression-Free Survival (PFS) is measured from date of start of treatment to the earliest occurrence of any of the following events: documented disease progression or death from any cause. Patients who are alive and progression-free will be censored at the date of last documented progression-free status which is the date of last tumor assessment according to RECIST v1.1. (NCT02834975)
Timeframe: Up to 48 months

Interventionmonths (Median)
Pembrolizumab, Paclitaxel + Carboplatin22.5

[back to top]

Pembro Combo vs Chemo: Change From Baseline to Week 18 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro combo arm and the chemo arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro arm and chemo arm and is presented later in the record." (NCT02853305)
Timeframe: Baseline, Week 18

InterventionScore on a Scale (Least Squares Mean)
Pembrolizumab + ST Chemotherapy (Pembro Combo)2.54
ST Chemotherapy (Chemo)-0.14

[back to top]

PFS Using RECIST 1.1 as Assessed by BICR at 6 Months

PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS was compared between arms as a pre-specified secondary analysis of the ITT population (all randomized participants). PFS is reported here for all participants at 6 months based on the product-limit (Kaplan-Meier) method for censored data. (NCT02853305)
Timeframe: 6 months

InterventionPercentage of Participants (Number)
Pembrolizumab + ST Chemotherapy (Pembro Combo)73.7
Pembrolizumab (Pembro)43.6
ST Chemotherapy (Chemo)70.3

[back to top]

PFS Using RECIST 1.1 as Assessed by BICR at 18 Months

PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS was compared between arms as a pre-specified secondary analysis of the ITT population (all randomized participants). PFS is reported here for all participants at 18 months based on the product-limit (Kaplan-Meier) method for censored data. (NCT02853305)
Timeframe: 18 months

InterventionPercentage of Participants (Number)
Pembrolizumab + ST Chemotherapy (Pembro Combo)23.0
Pembrolizumab (Pembro)19.1
ST Chemotherapy (Chemo)13.5

[back to top]

PFS Using RECIST 1.1 as Assessed by BICR at 12 Months

PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, PFS was compared between arms as a pre-specified secondary analysis of the ITT population (all randomized participants). PFS is reported here for all participants at 12 months based on the product-limit (Kaplan-Meier) method for censored data. (NCT02853305)
Timeframe: 12 months

InterventionPercentage of Participants (Number)
Pembrolizumab + ST Chemotherapy (Pembro Combo)33.7
Pembrolizumab (Pembro)26.6
ST Chemotherapy (Chemo)20.9

[back to top]

Pembro vs Chemo: TTD in the EORTC-QLQ-C30 GHS/QoL (Items 29 and 30) Combined Score

"EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD in GHS/QoL was defined as the time from first dose date to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score without confirmation. Per protocol, TTD in GHS/QoL combined score was compared between the pembro arm and chemo arm. TTD in GHS/QoL combined score was compared separately between the pembro combo arm and chemo arm and is presented earlier in the record." (NCT02853305)
Timeframe: Baseline up to approximately 25 months

InterventionMonths (Median)
Pembrolizumab (Pembro)3.6
ST Chemotherapy (Chemo)4.5

[back to top]

Pembro vs Chemo: OS in Participants With Programmed Cell Death Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥10%

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the CPS ≥10% subset of the pembro arm was compared to OS in the CPS ≥10% subset of the chemo arm for this endpoint as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro arm and chemo arm who were PD-L1 CPS ≥10%. Per protocol, OS in the CPS ≥10% subset of the pembro combo arm was not a pre-specified analysis of the ITT population and is not presented. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionMonths (Median)
Pembrolizumab (Pembro)16.1
ST Chemotherapy (Chemo)15.2

[back to top]

Pembro vs Chemo: OS

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro arm was compared to the chemo arm as a pre-specified primary analysis of the ITT population (all randomized participants). OS is reported here for all participants in the pembro arm and chemo arm. Per protocol, OS was compared separately between all participants of the pembro combo arm and chemo arm and is presented earlier in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionMonths (Median)
Pembrolizumab (Pembro)15.6
ST Chemotherapy (Chemo)14.3

[back to top]

Pembro vs Chemo: ORR Using RECIST 1.1 as Assessed by BICR

ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, ORR in the pembro arm was compared to the chemo arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro arm and chemo arm. Per protocol, ORR was compared separately between participants of the pembro combo arm and chemo arm and is presented earlier in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionPercentage of Participants (Number)
Pembrolizumab (Pembro)30.3
ST Chemotherapy (Chemo)44.9

[back to top]

Pembro vs Chemo: DOR Using RECIST 1.1 as Assessed by BICR

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. DOR is reported here for all participants in the pembro arm and chemo arm who had CR or PR. Per protocol, DOR was assessed separately in responders of the pembro combo arm and chemo arm and is presented earlier in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionMonths (Median)
Pembrolizumab (Pembro)28.2
ST Chemotherapy (Chemo)6.2

[back to top]

Pembro Combo vs Chemo: Progression-free Survival (PFS) Using Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

"PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study.~Per protocol, PFS in the pembro combo arm was compared to the chemo arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population (all randomized participants). PFS is reported here for all participants in the pembro combo arm and chemo arm. Per protocol, PFS was compared separately between all participants of the pembro arm and chemo arm and is presented later in the record." (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionMonths (Median)
Pembrolizumab + ST Chemotherapy (Pembro Combo)8.3
ST Chemotherapy (Chemo)7.1

[back to top]

Pembro Combo vs Chemo: Time to Deterioration (TTD) in the EORTC-QLQ-C30 GHS/QoL (Items 29 and 30) Combined Score

"EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. TTD in GHS/QoL was defined as the time from first dose date to the first onset of a ≥10 point decrease from baseline in GHS/QoL combined score without confirmation. Per protocol, TTD in GHS/QoL combined score was compared between the pembro combo arm and chemo arm. TTD in GHS/QoL combined score was compared separately between the pembro arm and chemo arm and is presented later in the record." (NCT02853305)
Timeframe: Baseline up to approximately 25 months

InterventionMonths (Median)
Pembrolizumab + ST Chemotherapy (Pembro Combo)8.0
ST Chemotherapy (Chemo)4.5

[back to top]

Pembro vs Chemo: Change From Baseline To Week 18 in the EORTC QLQ-C30 GHS/QoL Combined Score

"The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro arm and the chemo arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and chemo arm and is presented earlier in the record." (NCT02853305)
Timeframe: Baseline, Week 18

InterventionScore on a Scale (Least Squares Mean)
Pembrolizumab (Pembro)-1.89
ST Chemotherapy (Chemo)-0.95

[back to top]

Pembro vs Chemo: PFS Using RECIST 1.1 as Assessed by BICR

"PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study.~Per protocol, PFS in the pembro arm was compared to the chemo arm as a pre-specified analysis of the ITT population (all randomized participants). PFS is reported here for all participants in the pembro arm and chemo arm. Per protocol, PFS was compared separately between all participants of the pembro combo arm and chemo arm and is presented earlier in the record." (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionMonths (Median)
Pembrolizumab (Pembro)3.9
ST Chemotherapy (Chemo)7.1

[back to top]

Pembro Combo vs Chemo: Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS in the pembro combo arm was compared to the chemo arm as a pre-specified primary analysis of the ITT population (all randomized participants). OS is reported here for all participants in the pembro combo arm and chemo arm. Per protocol, OS was compared separately between all participants of the pembro arm and chemo arm and is presented later in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionMonths (Median)
Pembrolizumab + ST Chemotherapy (Pembro Combo)17.0
ST Chemotherapy (Chemo)14.3

[back to top]

Pembro vs Chemo: DCR Using RECIST 1.1 as Assessed by BICR

DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or SD (neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). Per protocol, DCR in the pembro arm was compared to the chemo arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by BICR was reported as the DCR for all participants in the pembro arm and chemo arm. Per protocol, DCR was compared separately between participants of the pembro combo arm and chemo arm and is presented earlier in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionPercentage of Participants (Number)
Pembrolizumab (Pembro)47.2
ST Chemotherapy (Chemo)75.9

[back to top]

Number of Participants Who Discontinue Study Drug Due to an AE

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that discontinued any study drug due to an AE was reported for each treatment arm. (NCT02853305)
Timeframe: Up to approximately 52 months

InterventionParticipants (Count of Participants)
Pembrolizumab + ST Chemotherapy (Pembro Combo)108
Pembrolizumab (Pembro)48
ST Chemotherapy (Chemo)62

[back to top]

Pembro Combo vs Chemo: Objective Response Rate (ORR) Using RECIST 1.1 as Assessed by BICR

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. The sponsor allowed a maximum of 10 target lesions in total and 5 per organ on this study. Per protocol, ORR in the pembro combo arm was compared to the chemo arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro combo arm and chemo arm. Per protocol, ORR was compared separately between participants of the pembro arm and chemo arm and is presented later in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionPercentage of Participants (Number)
Pembrolizumab + ST Chemotherapy (Pembro Combo)54.7
ST Chemotherapy (Chemo)44.9

[back to top]

Pembro Combo vs Chemo: Duration of Response (DOR) Using RECIST 1.1 as Assessed by BICR

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. DOR is reported here for all participants in the pembro combo arm and chemo arm who had CR or PR. Per protocol, DOR was assessed separately in responders of the pembro arm and chemo arm and is presented later in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionMonths (Median)
Pembrolizumab + ST Chemotherapy (Pembro Combo)8.5
ST Chemotherapy (Chemo)6.2

[back to top]

Pembro Combo vs Chemo: Disease Control Rate (DCR) Using RECIST 1.1 as Assessed by BICR

DCR was defined as the percentage of participants who had a confirmed CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD [at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). Per protocol, DCR in the pembro combo arm was compared to the chemo arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by BICR was reported as the DCR for all participants in the pembro combo arm and chemo arm. Per protocol, DCR was compared separately between participants of the pembro arm and chemo arm and is presented later in the record. (NCT02853305)
Timeframe: Up to approximately 42 months

InterventionPercentage of Participants (Number)
Pembrolizumab + ST Chemotherapy (Pembro Combo)80.3
ST Chemotherapy (Chemo)75.9

[back to top]

Number of Participants Who Experience an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. The number of participants that experienced at least one AE was reported for each treatment arm. (NCT02853305)
Timeframe: Up to approximately 55 months

InterventionParticipants (Count of Participants)
Pembrolizumab + ST Chemotherapy (Pembro Combo)348
Pembrolizumab (Pembro)289
ST Chemotherapy (Chemo)341

[back to top]

Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (Efficacy Population)

A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT02855944)
Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Interventionmonths (Median)
Rucaparib9.4
Chemotherapy7.2

[back to top]

Investigator Assessed Duration of Response (DOR) by RECIST v1.1 (ITT Population)

A secondary endpoint is the DOR for the Treatment Part of the study. The DOR as assessed by investigator is analyzed in the subgroup of patients who had a confirmed response by RECIST v1.1. DOR for any confirmed RECIST CR or PR will be measured from the date of the first response until the first date that progressive disease (PD) is documented. DOR is calculated in months as the time from the first date of the scan showing a response to the first scan with disease progression +1 day. Any patients with an ongoing response are censored at the date of the last post-baseline scan. Only tumor scans up to and within 6 weeks of start of any subsequent anti-cancer treatment are included. Progressive disease (PD) is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT02855944)
Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Interventionmonths (Median)
Rucaparib9.4
Chemotherapy7.2

[back to top]

Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (ITT Population)

A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. (NCT02855944)
Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Interventionpercentage of participants (Number)
Rucaparib37.9
Chemotherapy30.2

[back to top]

Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (ITT Population)

A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or response per Gynecologic Cancer InterGroup Cancer Antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response. (NCT02855944)
Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Interventionpercentage of patients (Number)
Rucaparib47.8
Chemotherapy40.5

[back to top]

Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (Efficacy Population)

The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT02855944)
Timeframe: Assessments every 8 weeks from Cycle 1 Day 1 (C1D1) until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

InterventionMonths (Median)
Rucaparib7.4
Chemotherapy5.7

[back to top]

Investigator Assessed Progression-Free Survival (invPFS) by RECIST Version 1.1 for Rucaparib Versus Chemotherapy (ITT Population)

The primary efficacy endpoint is invPFS for the Treatment Part of the study. The time to invPFS is calculated in months as the time from randomization to disease progression +1 day, as determined by RECIST v1.1 (Response Evaluation Criteria in Solid Tumors) criteria or death due to any cause, whichever occurs first. Progression is defined using RECIST v1.1, as at least a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT02855944)
Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

InterventionMonths (Median)
Rucaparib7.4
Chemotherapy5.7

[back to top]

Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (Efficacy Population)

EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed. (NCT02855944)
Timeframe: Baseline to the end of Cycle 6, or up to approximately 6 months

Interventionscore on a scale (Least Squares Mean)
Rucaparib0.5
Chemotherapy0.3

[back to top]

Least Squares Mean Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Global Health Status Score for the First 6 Cycles (ITT Population)

EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer patients. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Global scores are converted to a score of 0 to 100, with a higher score indicating improved health status. Mean changes from baseline global score over the first 6 cycles in the Treatment Part of the study were analyzed. (NCT02855944)
Timeframe: Baseline to the end of Cycle 6, or up to approximately 6 months

Interventionscore on a scale (Least Squares Mean)
Rucaparib0.6
Chemotherapy0.4

[back to top]

Overall Survival (Efficacy Population)

Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive. (NCT02855944)
Timeframe: All patients were followed for survival up to approximately 3.5 years.

InterventionMonths (Median)
Rucaparib21.1
Chemotherapy26.2

[back to top]

Overall Survival (ITT Population)

Overall survival (OS) is defined as the number of days from the date of randomization to the date of death (due to any cause). Patients who are still alive were censored on the date of their last available visit or last date known to be alive. (NCT02855944)
Timeframe: All patients were followed for survival up to approximately 3.5 years.

InterventionMonths (Median)
Rucaparib19.4
Chemotherapy25.4

[back to top]

Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 (Efficacy Population)

A secondary endpoint is the ORR for the Treatment Part of the study. ORR is defined as the percentage of patients with a confirmed CR (complete response) or PR (partial response) by RECIST v1.1. The confirmed response is defined as a CR or PR on subsequent tumor assessment at least 28 days after first response documentation. CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. (NCT02855944)
Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Interventionpercentage of participants (Number)
Rucaparib40.3
Chemotherapy32.3

[back to top]

Investigator Assessed Overall Response Rate (ORR) by RECIST v1.1 and/or CA-125 Response (Efficacy Population)

A secondary endpoint is ORR for the Treatment Part of the study defined as the percentage of patients with best response of CR or PR using RECIST v1.1 or response per Gynecologic Cancer InterGroup Cancer Antigen 125 (GCIG CA-125) criteria. Complete response (CR) is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Response to CA-125 has occurred if there is at least a 50% decrease from baseline: 1. in a sample collected after initiation of study treatment AND 2. that is confirmed in a subsequent sample collected ≥21 days after the prior sample. The absolute value of this confirmatory sample must be ≤110% of the prior sample. The date when the first sample with a 50% decrease from baseline is observed is the date of the CA-125 response. (NCT02855944)
Timeframe: Assessments every 8 weeks from C1D1 until disease progression, death, or initiation of subsequent treatment. After 18 months on study, assessments every 16 weeks. Total follow-up was up to approximately 3.5 years.

Interventionpercentage of patients (Number)
Rucaparib50.7
Chemotherapy43.6

[back to top]

Maximum Concentration (Cmax) of Epacadostat in Part A

Cmax was the maximum observed concentration of epacadostat in plasma for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, Cmax for Cohort 1 was measured on Days 1, 5, and 12 and Cmax for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). Cmax is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
InterventionnM (Geometric Mean)
Day 5
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab852
Part A Cohort 2: Epacadostat 25 mg+Pembrolizumab371

[back to top]

Maximum Concentration (Cmax) of Epacadostat in Part A

Cmax was the maximum observed concentration of epacadostat in plasma for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, Cmax for Cohort 1 was measured on Days 1, 5, and 12 and Cmax for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). Cmax is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
InterventionnM (Geometric Mean)
Day 1Day 5Day 12
Part A Cohort 1: Epacadostat 100 mg106011001200
Part A Cohort 1: Epacadostat 25 mg327269294

[back to top]

Terminal Half-Life (t1/2) of Epacadostat in Part A

t1/2 was the time required to divide the epacadostat concentration by two after reaching pseudo-equilibrium. Plasma t1/2 was measured for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, t1/2 for Cohort 1 was measured on Days 1, 5, and 12 and t1/2 for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). t1/2 is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
Interventionhours (Geometric Mean)
Day 5
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab3.77
Part A Cohort 2: Epacadostat 25 mg+Pembrolizumab2.62

[back to top]

Terminal Half-Life (t1/2) of Epacadostat in Part A

t1/2 was the time required to divide the epacadostat concentration by two after reaching pseudo-equilibrium. Plasma t1/2 was measured for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, t1/2 for Cohort 1 was measured on Days 1, 5, and 12 and t1/2 for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). t1/2 is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
Interventionhours (Geometric Mean)
Day 1Day 5Day 12
Part A Cohort 1: Epacadostat 100 mg2.552.822.43
Part A Cohort 1: Epacadostat 25 mg3.943.014.27

[back to top]

Number of Participants Who Discontinued Study Treatment Due to An Adverse Event (AE)

An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who discontinued due to an AE was reported for each arm. (NCT02862457)
Timeframe: Up to approximately 38.5 months

InterventionParticipants (Count of Participants)
Part A Cohort 1: Epacadostat 25 mg0
Part A Cohort 1: Epacadostat 100 mg1
Part A Cohort 2: Epacadostat 25 mg+Pembrolizumab0
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab1
Part B Cohort 1: Pembrolizumab+Cisplatin+Pemetrexed0
Part B Cohort 2: Pembrolizumab+Carboplatin+Pemetrexed3
Part B Cohort 3: Pembrolizumab+Carboplatin+Paclitaxel3

[back to top]

Time to Maximum Concentration (Tmax) of Epacadostat in Part A

Tmax was the time required to reach the maximum concentration of epacadostat in plasma for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, Tmax for Cohort 1 was measured on Days 1, 5, and 12 and Tmax for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). Tmax is presented as a Median with a full range. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
Interventionhours (Median)
Day 5
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab2.00
Part A Cohort 2: Epacadostat 25 mg+Pembrolizumab2.00

[back to top]

Time to Maximum Concentration (Tmax) of Epacadostat in Part A

Tmax was the time required to reach the maximum concentration of epacadostat in plasma for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, Tmax for Cohort 1 was measured on Days 1, 5, and 12 and Tmax for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). Tmax is presented as a Median with a full range. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
Interventionhours (Median)
Day 1Day 5Day 12
Part A Cohort 1: Epacadostat 100 mg2.002.002.00
Part A Cohort 1: Epacadostat 25 mg2.002.002.00

[back to top]

Trough Concentration (Ctrough) of Epacadostat in Part A

Ctrough was the lowest concentration of epacadostat in plasma just before the next dose for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, Ctrough for Cohort 1 was measured on Days 1, 5, and 12 and Ctrough for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). Ctrough is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose

,
InterventionnM (Geometric Mean)
Day 5
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab106.0
Part A Cohort 2: Epacadostat 25 mg+PembrolizumabNA

[back to top]

Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (NCI-CTCAE v.4.0)

A DLT was defined as the occurrence of any treatment-emergent adverse event occurring up to and including Study Day 7 for Part A Cohort 1 or Day 21 for Part A Cohort 2 and Part B. The following criteria defined DLTs: Grade (G) 4 thrombocytopenia; G4 neutropenia (despite optimal supportive care in Part B) lasting >1 week; febrile neutropenia (only if considered clinically significant in Part B); G4 toxicity; G3 laboratory abnormality lasting >1 week: G3 toxicity excluding nausea or vomiting controlled within 72 hours, rash in the absence of desquamation, no mucosal involvement, does not require systemic steroids, and resolves to G1 by the next scheduled dose of pembrolizumab or 14 days; G2 or higher episcleritis, uveitis, or iritis; unable to receive 75% of epacadostat or 1 dose of pembrolizumab during the DLT observation period because of toxicity, even if the toxicity does not meet DLT criteria; or >2 week delay in initiating Cycle 2 due to toxicity. (NCT02862457)
Timeframe: Up to Day 7 for Part A Cohort 1; up to Day 21 for Part A Cohort 2 and Part B

InterventionParticipants (Count of Participants)
Part A Cohort 1: Epacadostat 25 mg0
Part A Cohort 1: Epacadostat 100 mg0
Part A Cohort 2: Epacadostat 25 mg+Pembrolizumab0
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab1
Part B Cohort 1: Pembrolizumab+Cisplatin+Pemetrexed1
Part B Cohort 2: Pembrolizumab+Carboplatin+Pemetrexed2
Part B Cohort 3: Pembrolizumab+Carboplatin+Paclitaxel2

[back to top]

Trough Concentration (Ctrough) of Epacadostat in Part A

Ctrough was the lowest concentration of epacadostat in plasma just before the next dose for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, Ctrough for Cohort 1 was measured on Days 1, 5, and 12 and Ctrough for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). Ctrough is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose

,
InterventionnM (Geometric Mean)
Day 1Day 5Day 12
Part A Cohort 1: Epacadostat 100 mgNA87.795.4
Part A Cohort 1: Epacadostat 25 mgNANANA

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab in Part A Cycles 1, 2, 4, 6, and 8

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose for participants that received either dose regimen in Part A for Cohort 1 combined, Cohort 2 combined, and Cohorts 1+2 combined. Per protocol, blood sampling for Ctrough was taken at predose prior to the Cycle 1, 2, 4, 6, and 8 infusion. Cycle 1 length was 28 days (21-day pembrolizumab treatment cycle starting at Day 8 of Cycle 1). Cycle 2, 4, 6, and 8 length was 21 days. Ctrough is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Predose prior to the Cycles 1, 2, 4, 6, and 8 infusion

,,
Interventionµg/mL (Geometric Mean)
Cycle 1Cycle 2Cycle 4Cycle 6Cycle 8
Part A Combined Cohort 1NA17.324.528.538.2
Part A Combined Cohort 2NA17.941.851.047.9
Part A Combined Cohorts 1 And 2NA17.635.039.845.2

[back to top]

Trough Concentration (Ctrough) of Pembrolizumab in Part B Cycles 1, 2, 4, 6, and 8

Ctrough was the lowest concentration of pembrolizumab in serum just before the next dose for participants that received either dose regimen in Part B for Cohort 1, Cohort 2, Cohort 3, and Cohorts 1+2+3 combined. Per protocol, blood sampling for Ctrough was taken at pre-dose prior to the Cycle 1, 2, 4, 6, and 8 infusion. Cycle 1 length was 28 days (21-day pembrolizumab treatment cycle starting at Day 8 of Cycle 1). Cycle 2, 4, 6, and 8 length was 21 days. Ctrough is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Predose prior to the Cycles 1, 2, 4, 6, and 8 infusion

,,,
Interventionµg/mL (Geometric Mean)
Cycle 1Cycle 2Cycle 4Cycle 6Cycle 8
Part B Cohort 1: Pembrolizumab+Cisplatin+PemetrexedNA16.637.853.865.4
Part B Cohort 2: Pembrolizumab+Carboplatin+PemetrexedNA17.428.140.552.7
Part B Cohort 3: Pembrolizumab+Carboplatin+PaclitaxelNA8.6925.421.534.5
Part B Combined Cohorts 1, 2, and 3NA13.331.538.650.3

[back to top]

Area Under the Concentration-Time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) of Epacadostat in Part A

AUC0-t was defined as the AUC from zero to the time of the last measurable concentration of epacadostat in plasma for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, AUC0-t for Cohort 1 was measured on Days 1, 5, and 12 and AUC0-t for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). AUC0-t is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
InterventionnM•hour (Geometric Mean)
Day 1Day 5Day 12
Part A Cohort 1: Epacadostat 100 mg425046704710
Part A Cohort 1: Epacadostat 25 mg85510601020

[back to top]

Area Under the Concentration-Time Curve From Zero to the Time of the Last Measurable Concentration (AUC0-t) of Epacadostat in Part A

AUC0-t was defined as the AUC from zero to the time of the last measurable concentration of epacadostat in plasma for epacadostat administered alone (Cohort 1) and epacadostat administered with pembrolizumab (Cohort 2). Per protocol, AUC0-t for Cohort 1 was measured on Days 1, 5, and 12 and AUC0-t for Cohort 2 was measured on Day 5 only. Blood samples were collected pre-dose and post-dose at multiple time points up to 12 days during Cycle 1 (28-day cycle). AUC0-t is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (28-day cycle): Days 1, 5, and 12 at predose and 0.5, 1, 2, 4, 6, 8 and 10 hours postdose

,
InterventionnM•hour (Geometric Mean)
Day 5
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab3950
Part A Cohort 2: Epacadostat 25 mg+Pembrolizumab1260

[back to top]

Number of Participants Who Experienced At Least One Adverse Event (AE)

An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. The number of participants who experienced an AE was reported for each arm. (NCT02862457)
Timeframe: Up to approximately 39.7 months

InterventionParticipants (Count of Participants)
Part A Cohort 1: Epacadostat 25 mg3
Part A Cohort 1: Epacadostat 100 mg2
Part A Cohort 2: Epacadostat 25 mg+Pembrolizumab3
Part A Cohort 2: Epacadostat 100 mg+Pembrolizumab6
Part B Cohort 1: Pembrolizumab+Cisplatin+Pemetrexed7
Part B Cohort 2: Pembrolizumab+Carboplatin+Pemetrexed6
Part B Cohort 3: Pembrolizumab+Carboplatin+Paclitaxel6

[back to top]

Maximum Concentration (Cmax) of Pembrolizumab in Part B Cycle 1

Cmax was the maximum observed concentration of pembrolizumab in serum for participants that received either dose regimen in Part B for Cohort 1, Cohort 2, Cohort 3, and Cohorts 1+2+ 3 combined. Per protocol, the analysis for the Cmax of pembrolizumab was performed in Cycle 1 only. Blood samples were collected predose and postdose within 30 minutes post pembrolizumab infusion during Cycle 1 (21-day pembrolizumab treatment cycle starting at Day 8 of Cycle 1). Cmax is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (21-day pembrolizumab treatment cycle starting at Day 8 of Cycle 1): Day 1 predose and postdose within 30 minutes after the end of pembrolizumab infusion

Interventionµg/mL (Geometric Mean)
Part B Cohort 1: Pembrolizumab+Cisplatin+Pemetrexed73.8
Part B Cohort 2: Pembrolizumab+Carboplatin+Pemetrexed64.3
Part B Cohort 3: Pembrolizumab+Carboplatin+Paclitaxel65.3
Part B Combined Cohorts 1, 2, and 368.0

[back to top]

Maximum Concentration (Cmax) of Pembrolizumab in Part A Cycle 1

Cmax was the maximum observed concentration of pembrolizumab in serum for participants that received either dose regimen in Part A for Cohort 1 combined, Cohort 2 combined, and Cohorts 1+2 combined. Per protocol, the analysis for the Cmax of pembrolizumab was performed in Cycle 1 only. Blood samples were collected predose and postdose within 30 minutes post pembrolizumab infusion during Cycle 1 (21-day pembrolizumab treatment cycle starting at Day 8 of Cycle 1). Cmax is presented as a geometric mean with a percent geometric coefficient of variation. (NCT02862457)
Timeframe: Cycle 1 (21-day pembrolizumab treatment cycle starting at Day 8 of Cycle 1): Day 1 predose and postdose within 30 minutes after the end of pembrolizumab infusion

Interventionµg/mL (Geometric Mean)
Part A Combined Cohort 180.0
Part A Combined Cohort 273.8
Part A Combined Cohorts 1 and 276.2

[back to top]

Objective Response Rate (ORR) by Blinded Independent Centralized Review (BICR)

"ORR is number of randomized participants who have confirmed best overall response (BOR) of complete response (CR) or partial response (PR) using RECIST v1.1 criteria by BICR assessment.~BOR is the best response designation, between randomization and objectively documented progression per RECIST v1.1 criteria by BICR or the date of subsequent anti-cancer therapy, whichever occurs first.~PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathological lymph nodes to <10 mm (whether target or non-target).~Radiographic tumor response assessments from Week 7 (± 7 days), then every 6 weeks (± 7 days) until Week 49 and every 12 weeks (± 7 days) thereafter, until disease progression, treatment discontinued, or the start of subsequent anti-cancer therapy.~CR+PR, confidence interval based on the Clopper and Pearson method." (NCT02864251)
Timeframe: From randomization to the date of objectively documented progression, date of death, or the date of subsequent therapy (up to approximately 67 months)

InterventionPercent of Participants (Number)
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy30.6
Arm B: Nivolumab Plus Ipilimumab13.7
Arm C: Platinum Doublet Chemotherapy26.7

[back to top]

Progression Free Survival (PFS) by Blinded Independent Centralized Review (BICR)

"PFS is defined as the time between the date of randomization and the date of first documented tumor progression, as determined by BICR (per RECIST v1.1 criteria), or death due to any cause, whichever occurs first.~Participants who died without reported progression will be considered to have progressed on the date of their death. Subsequent therapy was accounted for by censoring at the last evaluable tumor assessment on or prior to the date of subsequent therapy.~Progression is the appearance of one or more new lesions. RECIST - response evaluation criteria in solid tumors is a standard system to measure tumor response to treatment.~Based on Kaplan-Meier estimates" (NCT02864251)
Timeframe: From randomization to the date of first documented tumor progression or death (approximately 58 months)

InterventionMonths (Median)
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy5.59
Arm B: Nivolumab Plus Ipilimumab1.54
Arm C: Platinum Doublet Chemotherapy5.45

[back to top]

Overall Survival (OS)

"Overall Survival (OS) is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a participant was known to be alive.~Median based on Kaplan-Meier Estimates" (NCT02864251)
Timeframe: From randomization to the date of death due to any cause (up to approximately 67 months)

InterventionMonths (Median)
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy19.35
Arm B: Nivolumab Plus Ipilimumab17.12
Arm C: Platinum Doublet Chemotherapy15.90

[back to top]

12 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)

The PFSR at 12 months is defined as the percent of treated participants remaining progression free and surviving at 12 months since the first dosing date. Progression is the appearance of one or more new lesions. Point estimates are derived from Kaplan-Meier analyses. (NCT02864251)
Timeframe: 12 Months after first treatment dose

InterventionPercent of Participants (Number)
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy21.2
Arm B: Nivolumab Plus Ipilimumab12.2
Arm C: Platinum Doublet Chemotherapy15.9

[back to top]

9 Month Progression Free Survival Rates (PFSR) by Blinded Independent Centralized Review (BICR)

"The PFSR at 9 months is defined as the percent of treated participants remaining progression free and surviving at 9 months since the first dosing date. Progression is the appearance of one or more new lesions.~Point estimates are derived from Kaplan-Meier analyses." (NCT02864251)
Timeframe: 9 months after first treatment dose

InterventionPercent of Participants (Number)
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy25.9
Arm B: Nivolumab Plus Ipilimumab12.2
Arm C: Platinum Doublet Chemotherapy19.8

[back to top]

Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)

"DOR is the time between the date of first response (CR or PR) and the date of first documented disease progression as determined by Response Evaluation Criteria In Solid Tumors (RECIST 1.1) or death due to any cause (death occurring after re-treatment or randomization to new combination treatment was not included), whichever occurred first.~PR is at least a 30% decrease in the sum of diameters of target lesions, using the baseline sum diameters as reference. CR is disappearance of all target lesions and a reduction in the short axis of pathological lymph nodes to <10 mm (whether target or non-target).~Radiographic tumor response assessments from Week 7 (± 7 days), then every 6 weeks (± 7 days) until Week 49 and every 12 weeks (± 7 days) thereafter, until disease progression, treatment discontinued, or the start of subsequent anti-cancer therapy.~Participants who neither progress nor die were censored on the date of their last assessment.~Median computed using Kaplan-Meier method" (NCT02864251)
Timeframe: From randomization to the date of first documented disease progression or death due to any cause (approximately 67 months)

InterventionMonths (Median)
Arm A: Nivolumab Plus Platinum-doublet Chemotherapy6.67
Arm B: Nivolumab Plus Ipilimumab50.04
Arm C: Platinum Doublet Chemotherapy5.55

[back to top]

Overall Survival (OS) According to PD-L1 Expression Level

PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by overall survival (OS) analysis. (NCT02899299)
Timeframe: Up to 40 months

,
InterventionMonths (Median)
<1% PD-L1≥1% PD-L1
Treatment A17.2818.04
Treatment B16.4913.27

[back to top]

Objective Response Rate (ORR) According to PD-L1 Expression Level

PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by objective response rate (ORR) analysis. (NCT02899299)
Timeframe: Up to 40 months

,
InterventionPercentage of Participants (Number)
<1% PD-L1≥1% PD-L1
Treatment A21.143.5
Treatment B38.544.3

[back to top]

Overall Survival (OS)

Overall Survival was defined as the time from randomization to the date of death due to any cause. A participant who has not died was censored at last known date alive. (NCT02899299)
Timeframe: From randomization to the date of death (Up to 40 Months)

InterventionMonths (Median)
Treatment A18.07
Treatment B14.09

[back to top]

Disease Control Rate (DCR)

Disease Control Rate is defined as the percentage of all randomized participants whose Best Overall Response was Complete Response, Partial Response, Stable Disease or Non-CR/Non-PD per adapted m-RECIST and RECIST 1.1 as assessed by Blinded Independent Central Review (BICR). (NCT02899299)
Timeframe: Up to 40 months

InterventionPercentage of Participants (Number)
Treatment A76.6
Treatment B85.1

[back to top]

Objective Response Rate (ORR)

Objective Response Rate is defined as the percentage of randomized participants who achieve a best overall response of complete response or partial response per Blinded Independent Central Review (BICR) assessments (Per adapted m-RECIST for pleural mesothelioma and RECIST 1.1, confirmation of response required). (NCT02899299)
Timeframe: Up to 40 months

InterventionPercentage of Participants (Number)
Treatment A39.6
Treatment B42.7

[back to top]

Progression Free Survival (PFS) According to PD-L1 Expression Level

PD-L1 Expression is defined as the percent of tumor cells membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 immunohistochemistry (IHC) assay. This is referred to as quantifiable PD-L1 expression and efficacy is determined by progression free survival (PFS) analysis. (NCT02899299)
Timeframe: Up to 40 months

,
InterventionMonths (Median)
<1% PD-L1≥1% PD-L1
Treatment A4.146.97
Treatment B8.317.06

[back to top]

Progression Free Survival (PFS)

Progression Free Survival is defined as the time between the date of randomization and the date of first documented tumor progression per Blinded Independent Central Review (BICR) assessments (using adapted m-RECIST and RECIST 1.1), or death due to any cause, whichever occurs first. Participants who received subsequent anticancer therapy prior to documented progression were censored at the date of the last evaluable tumor assessment conducted on or prior to the date of initiation of the subsequent anticancer therapy. (NCT02899299)
Timeframe: Up to 40 months

InterventionMonths (Median)
Treatment A6.77
Treatment B7.20

[back to top]

Apparent Clearance of Drug at Steady State at Steady State (CLss/F)

Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)

InterventionLitre/hour (Geometric Mean)
Ceralasertib (AZD6738)NA
Olaparib4.416

[back to top]

Time to Response (TTR)

The TTR (per RECIST 1.1 as assessed by the Investigator) was defined as the time from the date of first dose until the first date of documented response. (NCT02937818)
Timeframe: Until disease progression or data cut-off or Death (Up to 3.5 Years)

InterventionMonths (Median)
Arm A: Durvalumab + Tremelimumab (Original Cohort)1.8
Arm A: Durvalumab + Tremelimumab (Expansion Cohort)1.8
Arm C: Ceralasertib (AZD6738) + Olaparib1.7

[back to top]

Serum Concentrations of Durvalumab and Tremelimumab

Serum concentrations of Durvalumab and Tremelimumab are reported. (NCT02937818)
Timeframe: Durvalumab: Cycle 1 (each cycle was 4 weeks) Day 1(post-dose); Cycle 2 Day 1(pre-dose); Cycle 5 Day 1 (pre-dose); Tremelimumab: Cycle 1 (each cycle was 4 weeks) Day 1 (post-dose); Cycle 2 Day 1 (pre-dose); Cycle 5 Day 1 (No dose); Cycle 7 Day 1 (No dose)

Interventionμg/mL (Geometric Mean)
Durvalumab: Cycle 1 Day 1 (Post-dose)Durvalumab: Cycle 2 Day 1 (Pre-dose)Durvalumab: Cycle 5 Day 1 (Pre-dose)Tremelimumab: Cycle 1 Day 1 (Post-dose)Tremelimumab: Cycle 2 Day 1 (Pre-dose)Tremelimumab: Cycle 5 Day 1 (No dose)Tremelimumab: Cycle 7 Day 1 (No dose)
Arm A: Durvalumab + Tremelimumab (Original Cohort)391.19255.590116.84618.2992.6505.0050.784

[back to top]

Plasma Concentrations of Adavosertib and Carboplatin

Plasma concentrations of Adavosertib and Carboplatin are reported. (NCT02937818)
Timeframe: Adavosertib: Cycle 1 (each cycle was 21 days) Day 3 (pre-dose and post-dose); Cycle 3 Day 3 (pre-dose and post-dose); Carboplatin: Cycle 1 (each cycle was 21 days) Day 1 (post-dose)

InterventionnM (Geometric Mean)
Adavosertib: Cycle 1 Day 3 (Pre-dose)Adavosertib: Cycle 1 Day 3 (Post-dose)Adavosertib: Cycle 3 Day 3 (Pre-dose)Adavosertib: Cycle 3 Day 3 (Post-dose)Carboplatin: Cycle 1 Day 1 (Post-dose)
Arm B: Adavosertib + Carboplatin551.489728.342606.571805.27012834.615

[back to top]

Area Under the Concentration-time Curve at Steady State (AUCss)

Area under the concentration-time curve at steady state at steady state for Ceralasertib and Olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)

Interventionh*µg/mL (Geometric Mean)
Ceralasertib (AZD6738)NA
Olaparib67.929

[back to top]

Duration of Response (DoR)

The DoR was defined as the time from the date of first documented response (which was subsequently confirmed) CR/PR until the date of documented progression, or death in the absence of disease progression. The DoR in participants with confirmed objective response are reported. (NCT02937818)
Timeframe: Until disease progression or data cut-off or Death (Up to 3.5 Years)

InterventionMonths (Median)
Arm A: Durvalumab + Tremelimumab (Original Cohort)NA
Arm A: Durvalumab + Tremelimumab (Expansion Cohort)3
Arm C: Ceralasertib (AZD6738) + Olaparib8.5

[back to top]

Maximum Concentration (Cmax)

Maximum concentration for ceralasertib and olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose)

Interventionµg/mL (Geometric Mean)
Ceralasertib (AZD6738)4.215
Olaparib6.558

[back to top]

Maximum Concentration at Steady State (Cmax,ss)

Maximum concentration at steady state for Ceralasertib and Olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)

Interventionµg/mL (Geometric Mean)
Ceralasertib (AZD6738)5.176
Olaparib9.189

[back to top]

Minimum Concentration at Steady State (Cmin,ss)

Minimum concentration at steady state for Ceralasertib and Olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)

Interventionµg/mL (Geometric Mean)
Ceralasertib (AZD6738)1.119
Olaparib2.376

[back to top]

Number of Participants With Overall Response

Overall Response Rate (ORR) using Investigator assessments according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1. ORR was defined as the number (percentage) of participants with a confirmed Complete Response (CR) or confirmed Partial Response (PR) and was estimated for each treatment arm with corresponding 2-sided 95% exact confidence intervals (CIs). A confirmed response of CR/PR meant that a response of CR/PR was recorded at one visit and confirmed by repeat imaging, preferably at the next regularly scheduled imaging visit, and not less than 4 weeks after the visit when the response was first observed, with no evidence of progression between the initial and CR/PR confirmation visit. (NCT02937818)
Timeframe: Until disease progression [PD] (Up to 3.5 Years)

InterventionParticipants (Count of Participants)
Arm A: Durvalumab + Tremelimumab (Original Cohort)2
Arm A: Durvalumab + Tremelimumab (Expansion Cohort)1
Arm B: Adavosertib + Carboplatin0
Arm C: Ceralasertib (AZD6738) + Olaparib1

[back to top]

Progression Free Survival (PFS)

The PFS (per RECIST 1.1 according to the Investigator's assessment) was defined as the time from the date of the first dose of study treatment until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the participant withdrew from allocated therapy or received another anti-cancer therapy prior to progression. (NCT02937818)
Timeframe: Until disease progression or data cut-off or Death (Up to 3.5 Years)

InterventionMonths (Median)
Arm A: Durvalumab + Tremelimumab (Original Cohort)1.91
Arm A: Durvalumab + Tremelimumab (Expansion Cohort)1.77
Arm B: Adavosertib + Carboplatin2.60
Arm C: Ceralasertib (AZD6738) + Olaparib2.92

[back to top]

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is the development of an undesirable medical condition or the deterioration of a pre-existing medical condition following or during exposure to a pharmaceutical product, whether or not considered causally related to the product. SAE is an AE that results in any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a significant medical event. (NCT02937818)
Timeframe: Day 1 until disease progression, and follow-up visit (Up to 3.5 Years)

,,,
InterventionParticipants (Count of Participants)
Any AEAny AE causally related to any study treatmentAny AE with outcome = deathAny SAEAny AE leading to discontinuation of any study treatment
Arm A: Durvalumab + Tremelimumab (Expansion Cohort)179084
Arm A: Durvalumab + Tremelimumab (Original Cohort)1610162
Arm B: Adavosertib + Carboplatin88141
Arm C: Ceralasertib (AZD6738) + Olaparib1816171

[back to top]

Area Under the Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUC0-t)

Area under the concentration-time curve from time zero to the last measurable concentration for Ceralasertib and Olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose)

,
Interventionh*µg/mL (Geometric Mean)
Cycle 1, Day 1Cycle 1, Day 7
Ceralasertib (AZD6738)18.57524.061
Olaparib26.97362.535

[back to top]

Time to Maximum Concentration (Tmax)

Time to maximum concentration for ceralasertib and olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose)

InterventionHour (Median)
Ceralasertib (AZD6738)1.250
Olaparib1.800

[back to top]

Time to Maximum Concentration at Steady State (Tmax,ss)

Time to maximum concentration at steady state for Ceralasertib and Olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 7 (pre-dose and post-dose)

InterventionHour (Median)
Ceralasertib (AZD6738)1.875
Olaparib2.708

[back to top]

Partial Area Under the Concentration-time Curve (AUC0-6)

Partial area under the concentration-time curve for ceralasertib and olaparib are reported. (NCT02937818)
Timeframe: Cycle 1 (each cycle was 28 days in length) Day 1 (post-dose) and Cycle 1 Day 7 (pre-dose and post-dose)

,
Interventionh*µg/mL (Geometric Mean)
Cycle 1, Day 1Cycle 1, Day 7
Ceralasertib (AZD6738)18.34623.666
Olaparib26.35642.016

[back to top]

Overall Survival (OS)

The OS was defined as the time from the date of the first dose of study treatment until death due to any cause. (NCT02937818)
Timeframe: Until disease progression or data cut-off or Death (Up to 3.5 Years)

InterventionMonths (Median)
Arm A: Durvalumab + Tremelimumab (Original Cohort)5.95
Arm A: Durvalumab + Tremelimumab (Expansion Cohort)3.37
Arm B: Adavosertib + Carboplatin4.67
Arm C: Ceralasertib (AZD6738) + Olaparib7.56

[back to top]

Percentage of Participants With Disease Control at 12 Weeks

The disease control rate (DCR) at 12 weeks was defined as the percentage of participants who had a best objective response of CR or PR in the first 13 weeks or who had demonstrated stable disease (SD) for a minimum interval of 11 weeks following the start of study treatment. The DCR was determined programmatically based on RECIST 1.1 using site Investigator data and all data up until the first progression event. (NCT02937818)
Timeframe: At 12 Weeks

InterventionPercentage of Participants (Number)
Arm A: Durvalumab + Tremelimumab (Original Cohort)38.1
Arm A: Durvalumab + Tremelimumab (Expansion Cohort)15.0
Arm B: Adavosertib + Carboplatin30.0
Arm C: Ceralasertib (AZD6738) + Olaparib38.1

[back to top]

Objective Response Rate (ORR) at Cycle 3 and at Cycle 6 of Combination Therapy

"Objective response rate defined as the percentage of participants achieving a complete response (CR) and or partial response (PR) after treatment with NOX66 and carboplatin therapy as assessed by Response Evaluation Criteria in solid tumors (RECIST) v1.1.~CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to <10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and no new lesions." (NCT02941523)
Timeframe: Radiological evaluation at baseline and at 3 months and at 6 months

,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial Response
NOX66 400 mg + Carboplatin (AUC4) to Cycle 300
NOX66 400 mg + Carboplatin (AUC6) to Cycle 600
NOX66 800 mg + Carboplatin (AUC4) to Cycle 300
NOX66 800 mg + Carboplatin (AUC6) to Cycle 601

[back to top]

Overall Clinical Response Rate at Cycle 3 and at Cycle 6 of Combination Therapy

"Overall Clinical response rate defined as the percentage of participants who achieved complete response (CR) or partial response (PR) or stable disease (SD) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST) criteria v1.1 after combination of NOX66 and carboplatin therapy.~CR defined as disappearance of all target and non-target lesions and reduction of any pathological lymph nodes (whether target or non-target) to <10 mm in short axis; PR was defined by a 30% or more decrease in sum of longest diameter (SLD) of target lesions in reference to baseline. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions." (NCT02941523)
Timeframe: Radiological evaluation at baseline and at 3 months and at 6 months

InterventionParticipants (Count of Participants)
NOX66 400 mg + Carboplatin (AUC4) to Cycle 34
NOX66 400 mg + Carboplatin (AUC6) to Cycle 61
NOX66 800 mg + Carboplatin (AUC4) to Cycle 37
NOX66 800 mg + Carboplatin (AUC6) to Cycle 65

[back to top] [back to top]

Number of Participants Who Experience Dose Limiting Toxicity (DLT) During NOX66 Monotherapy and During NOX66 Combination With Carboplatin

Dose limiting toxicity during monotherapy and combination therapy defined as any Grade 3 or more toxicity (by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE version 4.03]) (related to therapy) excluding Grade 3 or more neutropenia lasting greater than 5 days or thrombocytopenia associate with bleeding or Grade 4 thrombocytopenia. (NCT02941523)
Timeframe: Up to 1 month for NOX66 monotherapy from enrollment and up to 7 months from start of NOX66 combination therapy

InterventionParticipants (Count of Participants)
NOX66 400 mg Monotherapy0
NOX66 400 mg Combination Therapy0
NOX66 800 mg Monotherapy0
NOX66 800 mg Combination Therapy0

[back to top]

Objective Response Rate

ORR（objective response rate）was defined as the percentage of participants in the analysis population who had a Complete Response or a Partial Response per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. Overall Response (OR) = CR + PR. (NCT02954172)
Timeframe: 18 weeks

Interventionpercentage of participants (Number)
Bevacizumab in Combination With Paclitaxel/Carboplatin46.4
IBI305 in Combination With Paclitaxel/Carboplatin44.3

[back to top]

Overall Survival Time

OS was defined as the time from randomization to death due to any cause. (NCT02954172)
Timeframe: 18.020 months

Interventionmonth (Median)
Bevacizumab in Combination With Paclitaxel/CarboplatinNA
IBI305 in Combination With Paclitaxel/Carboplatin18.020

[back to top]

Progression-free Survival

Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by Independent Radiological Review Committee.Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT02954172)
Timeframe: 18 months

Interventionmonths (Median)
Bevacizumab in Combination With Paclitaxel/Carboplatin8.260
IBI305 in Combination With Paclitaxel/Carboplatin8.430

[back to top]

Evaluation of Expression of Protein Programmed Death-Ligand 1 (PD-L1) Within Tumor, Stroma, and Infiltrating Immune Cells Combined, at Baseline and Following Immunotherapy.

To evaluate the correlation of pre-existing and post-immunotherapy immune response signatures with response to neoadjuvant chemotherapy. The number of PD-L1 positive cells (including tumor cells, lymphocytes, and macrophages) divided by the total number of tumor cells (PD-L1 positive or negative) in an area. (NCT02957968)
Timeframe: Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29

,,
InterventionNumber of PD-L1 positive cells (Mean)
Baseline (Bx 1)Post ImmunotherapyChange (Bx2-Bx1)
Cohort A: Triple Negative Breast Cancer (TNBC)31.0050.0019.00
Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab22.5035.5013.00
Cohort B: HER2-negative Hormone Receptor-positive Tumors13.0729.0716.00

[back to top]

Number of Adverse Events (AEs) Reported During and After Immune Treatment (ie, Decitabine and Pembrolizumab)

"Using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0), all adverse events (AEs) regardless of grade or attribution, will be captured from the beginning of study treatment (initiation of decitabine) until initiation of standard neoadjuvant chemotherapy.~For patients who do not initiate pembrolizumab, all AEs will be captured until 30 days following the last dose of decitabine or until another cancer treatment is initiated, whichever occurs first.For patients who initiate pembrolizumab, immune related adverse events (irAEs) (clinically significant and non-clinically significant) will be captured from the initiation of pembrolizumab through the end of the 30- day post-surgery (or post-treatment, for those who don't have surgery) follow-up period and at a 12-month follow-up time point." (NCT02957968)
Timeframe: Time of study registration until 30 days following the last dose of decitabine, or until another cancer treatment was initiated, or 30 days following surgery, 12- months.

InterventionAdverse Events Reported (Number)
Cohort A: Triple Negative Breast Cancer (TNBC)215
Cohort B: HER2-negative Hormone Receptor-positive Tumors151
Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab98

[back to top]

Number of Patients Meeting Criteria for Lymphocyte-predominant Breast Cancer (LPBC) Following Treatment With Decitabine and Pembrolizumab

To determine if the study treatment increases the proportion of tumors with ≥ 60% tumor or stromal area infiltrated with lymphocytes (ie, LPBC). The percentage of patients meeting criteria for LPBC following treatment with decitabine and pembrolizumab compared to the percentage before treatment (LPBC is defined as breast cancer with ≥ 60% intratumoral or stromal area with infiltrating lymphocytes.) (NCT02957968)
Timeframe: Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29

InterventionParticipants (Count of Participants)
Cohort A: Triple Negative Breast Cancer (TNBC)3
Cohort B: HER2-negative Hormone Receptor-positive Tumors0
Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab0

[back to top]

Number of Patients With Pathologic Complete Response (pCR) in the Breast and Post-therapy Lymph Nodes.

To determine the rate of pCR in the breast and lymph nodes (pCR breast and nodes). The number of patients with pCR in the breast and post-therapy lymph nodes defined as the absence of any invasive cancer in the resected breast specimen and absence of cancer on H&E evaluation of all resected lymph nodes following completion of neoadjuvant therapy (ypT0/is; ypN0). (NCT02957968)
Timeframe: 30 days following surgery or last dose of therapy

InterventionParticipants (Count of Participants)
Cohort A: Triple Negative Breast Cancer (TNBC)10
Cohort B: HER2-negative Hormone Receptor-positive Tumors3
Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab1

[back to top]

The Percentage of Increase in Tumor and Stroma With Infiltrating Lymphocytes (TIL) From Baseline Pre-treatment Biopsy to Post-immunotherapy Biopsy Following Administration of Decitabine Followed by Pembrolizumab.

To determine and quantify if treatment with neoadjuvant decitabine followed by pembrolizumab increases lymphocyte infiltration into tumor and/or stroma in patients with locally advanced, HER2-negative breast cancer. (NCT02957968)
Timeframe: Baseline pre-treatment biopsy to post-immunotherapy biopsy following administration of decitabine followed by pembrolizumab, 3-7 day window after Day 22 medication administration, about one month

,,
Intervention% of stromal area occupied by TIL (Mean)
BaselinePost TreatmentAbsolute Change Value
Cohort A: Triple Negative Breast Cancer (TNBC)27.3535.007.65
Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab25.8332.506.67
Cohort B: HER2-negative Hormone Receptor-positive Tumors17.5023.576.07

[back to top]

Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-decitabine Compared to MDSC Found in Blood Samples Collected at Baseline.

Evaluate the level of circulating MDSC per ml of blood at baseline, following treatment with decitabine alone. (NCT02957968)
Timeframe: Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29

,,
Interventionabsolute cell count per ml of blood (Mean)
Baseline GranulocyticPost Decitabine- GranulocyticChange- GranulocyticBaseline- MonocyticPost Decitabine- MonocyticChangeBaseline- Total-MDSCPost Decitabine- Total MDSCChange- Total MDSC
Cohort A: Triple Negative Breast Cancer (TNBC)13271.206279.00-6992.2059222.0520524.50-38697.5583927.6035606.00-48321.60
Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab77038.7143120.00-33918.7115843.2916081.57238.29138957.4392662.71-46294.71
Cohort B: HER2-negative Hormone Receptor-positive Tumors22575.5038759.5016184.0045450.3318886.00-26564.33213321.11146345.39-66975.72

[back to top]

Evaluation of Myeloid-derived Suppressor Cells (MDSC) Identified in Blood Samples Post-pembrolizumab Compared to MDSC Found in Blood Samples Collected at Baseline.

Evaluate the level of circulating MDSC per ml of blood at baseline, following treatment with pembrolizumab administered after decitabine. (NCT02957968)
Timeframe: Assessed at end of administration of decitabine and pembrolizumab Day- Window of time Days 25-29

,,
InterventionAbsolute cell count per ml of blood (Mean)
Baseline- GranulocyticPost Pembrolizumab- GranulocyticChange(Post Pembro-Baseline) GranulocyticBaseline- MonocyticPost Pembrolizumab- MonocyticChange (Post Pembro- Baseline)- MonocyticBaseline- Total MDSCPost Pembrolizumab- Total MDSCChange (Post Pembro-Baseline)- Total MDSC
Cohort A: Triple Negative Breast Cancer (TNBC)13271.2033099.4019828.2059222.0522499.95-36722.1083927.6074569.75-9357.85
Cohort A2: Triple Negative Breast Cancer (TNBC) With Extended Pembrolizumab77038.7163045.29-13993.4315843.2918028.432185.14138957.43133082.00-5875.43
Cohort B: HER2-negative Hormone Receptor-positive Tumors22575.5025780.333204.8345450.3321651.56-23798.78213321.1178836.72-134484.39

[back to top]

Terminal Elimination Half-Life (t1/2) of Free Carboplatin

t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve. (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Interventionhours (Median)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)5.23
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)2.49
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)1.79

[back to top]

Cumulative Dose of Gemcitabine

Cumulative dose: Sum of the total doses by cycle administered to a participant in the duration of exposure, i.e. total number of cycles received (milligram per meter square [mg/m^2]). (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

Interventionmg/m^2 (Mean)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)10694.3
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)14680.9
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)13277.2

[back to top]

Cumulative Dose of Carboplatin

Cumulative dose: Sum of the total doses by cycle (AUC) administered to a participant in the duration of exposure, i.e. total number of cycles received (in total prescribed AUC). (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

InterventionAUC (mg/mL/min) (Mean)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)20.3
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)27.8
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)26.0

[back to top]

Dose Modifications - Number of Participants With Skipped Doses

Dose modifications was summarized for each study drug based on skipped doses not received during the treatment period. Primary reasons for skipped doses included toxicity, investigator decision and administrative reasons (e.g., holidays). (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

InterventionParticipants (Count of Participants)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)15
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)20
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)13

[back to top]

Clearance (CL) of of Free Carboplatin

Clearance after intravenous infusion administration was calculated as: CL=Dose/AUC0-inf. AUC0-inf was calculated as: AUC0-inf=AUClast+Clast/lambdaz where Clast is the last quantifiable concentration in the terminal elimination phase. (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

InterventionLiter/hour (L/h) (Mean)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)6.65
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)14.0
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)13.7

[back to top]

Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Trilaciclib

AUC0-t was calculated with the linear/log-trapezoidal method, which uses linear interpolation between data points to calculate the AUC. The linear/log-trapezoidal method will be employed for all incremental trapezoids arising from increasing concentrations and the logarithmic trapezoidal method will be used for those arising from decreasing concentrations. (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Interventionhour* nanogram per milliliter (h*ng/mL) (Mean)
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)3610
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)3800

[back to top]

Area Under the Plasma Concentration-Time Curve From Time 0 to t Hours (AUC0-t) of Gemcitabine

AUC0-t was calculated with the linear/log-trapezoidal method. (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Interventionhour*microgram per milliliter (h*mcg/mL) (Mean)
Group 1: Gemcitabine/Carboplatin (Day 1 and 8)NA
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)20.4
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)15.4

[back to top]

Overall Survival (OS)

Overall survival was defined as the time (months) from date of randomization to the date of death due to any cause. Participants who do not die during the study were censored at the date last known to be alive. The OS was calculated using Kaplan-Meier method. (NCT02978716)
Timeframe: From date of randomization to date of death due to any cause, assessed up to a maximum of 1120 days

Interventionmonths (Median)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)12.6
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)NA
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)17.8

[back to top]

Number of Participants With Grade 3 or 4 Thrombocytopenia

"Hematologic toxicities events are defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 thrombocytopenia was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 thrombocytopenia during the treatment period, the participant was assigned as Yes to the occurrence of Grade 3 and 4 thrombocytopenia; otherwise, it was No. If a participant did not have an event, the value of 0 was assigned to that participant." (NCT02978716)
Timeframe: During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

InterventionParticipants (Count of Participants)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)21
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)12
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)19

[back to top]

Number of Participants With Febrile Neutropenia (FN)

"The criterion for identifying FN was if the PT was FEBRILE NEUTROPENIA the occurrence during the treatment period was defined as a binary variable (Yes or No); Yes if total number of events >=1 was observed, No for other scenarios. If a participant did not have an event, the value of 0 was assigned to that participant." (NCT02978716)
Timeframe: During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

InterventionParticipants (Count of Participants)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)1
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)1
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)0

[back to top]

Number of Cycles Participants Received Treatment in Each Treatment Arm

Participants were considered to have started a cycle if they have received at least 1 dose of any study drug. (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

Interventionnumber of cycles (Mean)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)6
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)9
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)8

[back to top]

Maximum Observed Plasma Concentration (Cmax) of Trilaciclib

The observed peak plasma concentration was determined from the plasma concentration-versus time data. (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Interventionng/mL (Mean)
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)2280
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)1630

[back to top]

Maximum Observed Plasma Concentration (Cmax) of Gemcitabine

The observed peak plasma concentration was determined from the plasma concentration-versus time data. (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Interventionmicrogram per milliliter (mcg/mL) (Mean)
Group 1: Gemcitabine/Carboplatin (Day 1 and 8)NA
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)18.0
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)23.8

[back to top]

Major Adverse Hematologic Event (MAHE) Rate

MAHE was a composite endpoint incorporating the measurement of several clinically meaningful aspects of myelosuppression into a single endpoint by summing of the total number of events across a set of pre-specified components.The individual components for MAHE were all-cause hospitalizations, all-cause dose reductions, febrile neutropenia, prolonged severe neutropenia (duration > 5 days), RBC transfusion and platelet transfusion. Event rate for MAHE was calculated as the number of events/durations of treatment period divided by 7 days/1 week. (NCT02978716)
Timeframe: During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Interventionevent rate per week (Number)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)0.153
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)0.108
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)0.080

[back to top]

Duration of Severe (Grade 4) Neutropenia (DSN) During Cycle 1

DSN was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of less than (<) 0.5 × 10^9 cells/liter (L) observed between Day 1 Cycle 1 and the end of Cycle 1 to the date of the first ANC value greater than or equal to (>=) 0.5 × 10^9/L that met the following: (1) occurred after the ANC value of < 0.5 × 10^9 cells/L and (2) no other ANC values < 0.5 × 10^9 cells/L occurred between this day and the end of Cycle 1. Severe neutropenia (SN) was set to zero for participants who did not experience severe (Grade 4) neutropenia in Cycle 1, including those who were randomized but never treated. (NCT02978716)
Timeframe: From randomization to the end of Cycle 1 (Each cycle= 21 days)

Interventiondays (Mean)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)1
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)2
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)1

[back to top]

Duration of Objective Response (DOR) as Per RECIST v1.1 as Determined by Investigator

DOR is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Participants who do not experience PD or death was censored at the last tumor assessment date. 95% Confidence Interval (CI) was calculated using the Kaplan-Meier method. (NCT02978716)
Timeframe: From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days

Interventionmonths (Median)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)7.8
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)11.5
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)9.6

[back to top]

Duration of Exposure

Duration of exposure (days) = First dose date of study drug from the last cycle - first dose date of study drug + 21. (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

Interventiondays (Median)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)101
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)161
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)168

[back to top]

Dose Modifications: Number of Participants With Cycle Delays

Dose modifications was summarized for each study drug based on number of cycles received during the treatment period. If the participant was unable to start a new cycle at that next visit, then the cycle is delayed, the reason entered, and the question was asked again at the next visit until the participant either starts a new cycle or discontinues treatment. (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

InterventionParticipants (Count of Participants)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)17
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)19
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)22

[back to top]

Relative Dose Intensity of Gemcitabine and Carboplatin

Relative dose intensity was defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity was defined as the cumulative planned dose through the study divided by (number of cycles × 3 weeks). Relative dose intensity (%) was calculated as: for gemcitabine (100 * [Dose intensity (mg/m2/week) / (2000/3 (mg/m2/week)]); for carboplatin (100 * [Dose intensity (AUC/week)/ (4/3) (AUC/week)]) and for trilaciclib (100 * [Dose intensity (mg/m2/week)/ (480 /3 (mg/m2/week)] for Group 2 and 100 * [Dose intensity (mg/m2/week) / (960 /3 (mg/m2/week)] for Group 3). (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

,,
Interventionpercentage of dose (Mean)
CarboplatinGemcitabine
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)77.579.1
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)79.180.8
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)81.781.0

[back to top]

Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

An Adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product that did not necessarily have a causal relationship with this treatment. Any AE that started on or after the first dose of study drugs was included as a TEAE. A Serious AE was defined as any AE, occurring at any dose (including after the informed consent form was signed and prior to dosing) and regardless of causality that met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. TEAEs included serious and non-serious TEAEs. (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 1116 days

,,
InterventionParticipants (Count of Participants)
Participants with any TEAEsParticipants with any Serious TEAEs
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)3010
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)3311
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)344

[back to top]

Number of Participants With Grade 3 and 4 Hematologic Toxicities

Hematologic toxicities events were defined as any cycle where any hematologic lab value occurs that meets the CTCAE toxicity grade criteria for >= Grade 3 and the value is treatment emergent. The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a participant had at least 1 cycle with at least one Grade 3 or 4 hematologic toxicities during the treatment period, the participant was assigned as Yes to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was No. If a participant did not have an event, the value of 0 was assigned to that participant. (NCT02978716)
Timeframe: During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

,,
InterventionParticipants (Count of Participants)
Participants with Grade 3 and 4 hematologic toxicities: YesParticipants with Grade 3 and 4 hematologic toxicities: No
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)259
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)303
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)278

[back to top]

Number of Participants With Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

BOR was defined as the best response across all time points (RECIST v1.1). The best overall response was determined once all the data for the participant is known. Each participant has been assigned one of the following categories (RECIST 1.1): complete response (CR): disappearance of all target lesions; partial response (PR): >= 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters; progression disease (PD): >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study); stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD); NE: not evaluable and missing. (NCT02978716)
Timeframe: From date of randomization until the occurrence of progressive disease or a censoring event, assessed up to a maximum of 875 days

,,
InterventionParticipants (Count of Participants)
Complete response (CR)Partial response (PR)Stable disease (SD)Progressive disease (PD)Not evaluable (NE)Missing
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)0711600
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)0159501
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)01115311

[back to top]

Dose Modifications: Number of Participants With Any Dose Interruptions

Dose interruptions was defined as interruption of infusion, regardless of whether the study drug was continued after the interruption. (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

,,
InterventionParticipants (Count of Participants)
TrilaciclibCarboplatinGemcitabine
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)NA12
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)314
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)500

[back to top]

Dose Modifications - Number of Participants With Dose Reductions

Dose (mg/m2) reductions were not permitted for trilaciclib. Dose reductions for carboplatin and gemcitabine were determined by comparing the planned dose on the respective drug administration pages between the current cycle and the previous cycle. (NCT02978716)
Timeframe: During the treatment period. From date of first dose, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 871 days

,,
InterventionParticipants (Count of Participants)
CarboplatinGemcitabine
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)1013
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)1320
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)1517

[back to top]

Volume of Distribution at Steady State (Vss) of Free Carboplatin

Vss was the volume of distribution at steady state of free carboplatin was reported. (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

InterventionLiter (Mean)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)44.4
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)35.0
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)34.0

[back to top]

Terminal Elimination Half-Life (t1/2) of Trilaciclib

t1/2 was calculated as 0.693 divided by lambda z. lambda z (terminal phase rate constant) was determined by linear regression of at least 3 points on the terminal phase of the log-linear plasma concentration-time curve, the actual body exposure to drug after administration of a dose of the drug ( in mg*h/L). (NCT02978716)
Timeframe: Cycle 1 Day 1 (Group 1): Pre-dose, 0.5, 1, 2, 3.5, 5, 24 hours post-dose; Cycle 1 Day 1 (Group 2) and Cycle 1 Day 2 (Group 3): Pre-dose, 0.5, 1, 1.5, 2.5, 4, 5.5, 24 hours post-dose (Each cycle is of 21 days)

Interventionhours (Median)
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)5.27
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)5.31

[back to top]

Progression Free Survival (PFS) as Per RECIST v1.1 as Determined by Investigator

PFS was defined as the time (months) from date of randomization until date of documented PD or death due to any cause, whichever comes first. PD: >= 20% increase in the sum of diameters of target lesions (taking as reference the smallest sum on study). The PFS was calculated using Kaplan-Meier method. (NCT02978716)
Timeframe: From date of randomization until the occurrence of disease progression, death due to any cause or a censoring event, assessed up to a maximum of 875 days

Interventionmonths (Median)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)5.7
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)9.4
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)7.3

[back to top]

All-cause Dose Reductions, Event Rate (Per Cycle)

Dose reductions were not permitted for trilaciclib. Dose reductions for gemcitabine or carboplatin were collected on the dosing page. No more than 3 dose modifications for toxicity in total were allowed for any participant. All dose reductions were counted as a separate event. Discontinuations of an individual component of the chemotherapy regimen were counted as a dose reduction If the participant continued the other chemotherapy drug as a monotherapy. Event rate was calculated as the total number of cycles with an event divided by the total number of cycles. (NCT02978716)
Timeframe: During the treatment period. From date of randomization, 21 day treatment cycles continue until disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 542 days

Interventionevent rate per cycle (Number)
Group 1: Gemcitabine/Carboplatin (Days 1 and 8)0.141
Group 2: Trilaciclib + Gemcitabine/Carboplatin (Days 1 and 8)0.118
Group 3: Trilaciclib (Days 1, 2, 8 and 9) + Gemcitabine/Carboplatin (Days 2 and 9)0.133

[back to top]

Part 3 Schedule Finding: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window

Part 3 of the study was a schedule finding phase to establish the recommended phase 2 dosing schedules for Part 4 and assess the safety and tolerability for the NKTR-214/nivolumab/ipilimumab triplet combination. The results presented are for the DLT Population. (NCT02983045)
Timeframe: Dose-limiting toxicities (DLTs) were assessed during a 3-week (21-day) DLT evaluation period beginning with the first dose of ipilimumab.

,,
InterventionParticipants (Count of Participants)
Patients with at least one eventEndocrine disorders: Adrenal insufficiencyEndocrine disorders: HyperthyroidismMetabolism and nutrition disorders: Hyponatraemia
Schedule Finding (Schedule 1): NKTR-214 + Nivolumab + Ipilimumab1001
Schedule Finding (Schedule 2): NKTR-214 + Nivolumab + Ipilimumab1100
Schedule Finding (Schedule 3): NKTR-214 + Nivolumab + Ipilimumab1010

[back to top]

Part 1 Dose Escalation: Incidence of Dose-limiting Toxicity (DLT) During the DLT Evaluation Window

Part 1of the study was a dose-escalation phase that evaluated the safety and tolerability and defined the maximum tolerated dose or recommended Phase 2 dose of the NKTR-214/nivolumab doublet across 5 dosage/schedule levels. The results presented are for the DLT Population. (NCT02983045)
Timeframe: Includes DLTs that occurred within the DLT window of at least 21 days after the first dose of study treatment (28 days for every 2 weeks dosing; 21 days for every 3 weeks dosing). Patients were counted only once under each preferred term.

,,,,
InterventionParticipants (Count of Participants)
At least 1 DLTMetabolism and Nutrition Disorders: AcidosisMetabolism and Nutrition Disorders: HyperglycaemiaVascular Disorders: Hypotension
Dose Escalation Cohort 1: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (240 mg) q2w0000
Dose Escalation Cohort 2: NKTR-214 (0.006 mg/kg) q2w + Nivolumab (240 mg) q2w0000
Dose Escalation Cohort 3: NKTR-214 (0.003 mg/kg) q2w + Nivolumab (240 mg) q2w0000
Dose Escalation Cohort 4: NKTR-214 (0.006 mg/kg) q3w + Nivolumab (360 mg) q3w0000
Dose Escalation Cohort 5: NKTR-214 (0.009 mg/kg) q3w + Nivolumab (360 mg) q3w2111

[back to top] [back to top]

Percentage of Patients Achieving >= 50% Reduction in PSA According to Prostate Cancer Working Group 3 (PCWG3) Criteria

Achievement of a PSA50 decline is whether the treatment results in a 50% or greater decline in PSA from baseline PSA prior to therapy (NCT02985021)
Timeframe: From Day 1 of treatment and up to 30 days after completion of treatment (typically up to 10 cycles of chemotherapy)

InterventionParticipants (Count of Participants)
Treatment (Docetaxel, Carboplatin)2

[back to top]

Pathologic Complete Response (pCR) Rate

Pathologic complete response (pCR) rate is defined as the number of randomized participants with absence of residual tumor in lung and lymph nodes as evaluated by blinded independent pathological review (BIPR). (NCT02998528)
Timeframe: From randomization up to a median of 30 months after randomization.

InterventionParticipants (Count of Participants)
Arm B: Platinum Doublet Chemo4
Arm C: Nivo 360 mg + Platinum Doublet Chemo43

[back to top]

Major Pathologic Response (MPR) Rate

Major pathologic response (MPR) rate is defined as number of randomized participants with NCT02998528)
Timeframe: From randomization up to a median of 30 months after randomization.

InterventionParticipants (Count of Participants)
Arm B: Platinum Doublet Chemo16
Arm C: Nivo 360 mg + Platinum Doublet Chemo66

[back to top]

Time to Death or Distant Metastases (TTDM)

TTDM is defined as the time between the date of randomization and the first date of distant metastasis or the date of death in the absence of distant metastasis. Distant metastasis is defined as any new lesion that is outside of the thorax using blinded independent central review (BICR) according to response evaluation criteria in solid tumors (RECIST) 1.1. Patients who have not developed distant metastasis or died at the time of analysis will be censored on the date of their last evaluable tumor assessment. (NCT02998528)
Timeframe: From randomization to the first date of distant metastasis or the date of death in the absence of distant metastasis (Up to a median of 30 months)

InterventionMonths (Median)
Arm B: Platinum Doublet Chemo26.71
Arm C: Nivo 360 mg + Platinum Doublet ChemoNA

[back to top]

Event-Free Survival (EFS)

Event-free survival (EFS) is defined as the length of time from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on blinded independent central review (BICR) assessment per response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). (NCT02998528)
Timeframe: From randomization to disease progression, reoccurrence, or death due to any cause. (Up to a median of 30 months)

InterventionMonths (Median)
Arm B: Platinum Doublet Chemo20.80
Arm C: Nivo 360 mg + Platinum Doublet Chemo31.57

[back to top]

PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% Analysis Set

The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab5.6
Platinum-based SoC4.5

[back to top]

DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% Analysis Set

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab12.2
Platinum-based SoC4.2

[back to top]

DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=25% LREM Analysis Set

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab11.6
Platinum-based SoC4.2

[back to top]

APF12 in PD-L1 TC >= 50% LREM Analysis Set

The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. (NCT03003962)
Timeframe: From date of randomization until 12 months

Interventionpercentage of participants (Number)
Durvalumab26.5
Platinum-based SoC14.5

[back to top]

APF12 in PD-L1 TC >= 50% Analysis Set

The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. (NCT03003962)
Timeframe: From date of randomization until 12 months

Interventionpercentage of participants (Number)
Durvalumab26.1
Platinum-based SoC11.7

[back to top]

APF12 in PD-L1 TC >= 25% LREM Analysis Set

The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. (NCT03003962)
Timeframe: From date of randomization until 12 months

Interventionpercentage of participants (Number)
Durvalumab24.1
Platinum-based SoC16.4

[back to top]

Alive and Progression-Free at 12 Months (APF12)

The APF12 was defined as the Kaplan-Meier estimate of percentage of participants alive and progression free at 12 months based on PFS (per RECIST 1.1 as assessed using Investigator assessments) analysis. (NCT03003962)
Timeframe: From date of randomization until 12 months

Interventionpercentage of participants (Number)
Durvalumab25.5
Platinum-based SoC13.3

[back to top]

OS at 24 Months in PD-L1 TC > = 25% LREM Analysis Set

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months. (NCT03003962)
Timeframe: From date of randomization till 24 months

Interventionpercentage of participants (Number)
Durvalumab34.7
Platinum-based SoC32.8

[back to top]

OS at 24 Months

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months. (NCT03003962)
Timeframe: From date of randomization till 24 months

Interventionpercentage of participants (Number)
Durvalumab34.6
Platinum-based SoC27.2

[back to top]

OS at 18 Months in PD-L1 TC >= 50% LREM Analysis Set

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. (NCT03003962)
Timeframe: From date of randomization till 18 months

Interventionpercentage of participants (Number)
Durvalumab44.3
Platinum-based SoC42.2

[back to top]

OS at 18 Months in PD-L1 TC >= 50% Analysis Set

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. (NCT03003962)
Timeframe: From date of randomization till 18 months

Interventionpercentage of participants (Number)
Durvalumab43.2
Platinum-based SoC34.9

[back to top]

OS at 18 Months in PD-L1 TC > = 25% LREM Analysis Set

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. (NCT03003962)
Timeframe: From date of randomization till 18 months

Interventionpercentage of participants (Number)
Durvalumab43.0
Platinum-based SoC41.4

[back to top]

OS at 18 Months

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 18 months were defined as the Kaplan-Meier estimate of OS at 18 months. (NCT03003962)
Timeframe: From date of randomization till 18 months.

Interventionpercentage of participants (Number)
Durvalumab42.5
Platinum-based SoC34.2

[back to top]

ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% LREM Analysis Set

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionpercentage of participants (Number)
Durvalumab44.0
Platinum-based SoC43.7

[back to top]

ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 50% Analysis Set

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionpercentage of participants (Number)
Durvalumab42.1
Platinum-based SoC40.7

[back to top]

ORR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >= 25% LREM Analysis Set

ORR (per RECIST 1.1 using Investigator assessments)was defined as the percentage of participants with an unconfirmed response of CR or PR. CR was defined as disappearance of all TLs. Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionpercentage of participants (Number)
Durvalumab38.5
Platinum-based SoC40.2

[back to top]

Objective Response Rate (ORR) as Per RECIST 1.1 Using Investigator Assessment

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of participants with an unconfirmed response of complete response (CR) or partial response (PR). CR was defined as disappearance of all target lesions (TLs). Any pathological lymph nodes selected as TLs had a reduction in short axis to < 10 millimeter (mm). PR was defined as at least a 30% decrease in the sum of diameters of TLs, with reference the baseline sum of diameters if criteria for PD are not met. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionpercentage of participants (Number)
Durvalumab37.6
Platinum-based SoC37.4

[back to top]

Duration of Response (DoR) as Per RECIST 1.1 Using Investigator Assessment

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab11.9
Platinum-based SoC4.2

[back to top]

DoR as Per RECIST 1.1 Using Investigator Assessment in PD-L1 TC >=50% LREM Analysis Set

DoR (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of first documented response until the first date of documented progression or death in the absence of disease progression (i.e. date of PFS event or censoring - date of first response + 1). DoR was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab12.2
Platinum-based SoC4.2

[back to top]

PFS Based on Investigator Assessment According to RECIST 1.1 in PD-L1 TC >= 50% LREM Analysis Set

The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab5.7
Platinum-based SoC5.5

[back to top]

PFS2 in PD-L1 TC >= 25% LREM Analysis Set

PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab11.8
Platinum-based SoC10.9

[back to top]

Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) 30-Item Core Quality of Life Questionnaire Version 3 (QLQ-C30)

The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months. (NCT03003962)
Timeframe: Baseline and 12 months

,
Interventionscores on a scale (Mean)
Global health statusPhysical functioningFatigueAppetite loss
Durvalumab-0.7-3.31.4-1.1
Platinum-based SoC-7.4-6.17.29.1

[back to top]

PFS2 in PD-L1 TC >= 50% Analysis Set

PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab11.3
Platinum-based SoC8.8

[back to top]

Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status

ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported. (NCT03003962)
Timeframe: From Baseline and until follow-up period of 57 months

,
Interventionnumber of participants (Number)
Restricted activity, BaselineRestricted activity, Follow-up Month 57
Durvalumab2670
Platinum-based SoC2552

[back to top]

Number of Participants With ECOG Performance Status in PD-L1 TC >=25% LREM Analysis Set

ECOG performance status was assessed at the times specified based on the following and scored as 0: fully active: able to carry out all usual activities without restrictions. 1: Restricted in strenuous activity, but ambulatory and able to carry out any work activities; up and about more than 50% of waking hours. 3: Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4: Completely disabled; unable to carry out any self-care and totally confined to bed or chair and 5: death. Data for only participants with restricted activity has been reported. (NCT03003962)
Timeframe: From Baseline and until follow-up period of 57 months

,
Interventionnumber of participants (Number)
Restricted activity, BaselineRestricted activity, Follow-up Month 57
Durvalumab2210
Platinum-based SoC2032

[back to top]

PFS2 in PD-L1 TC >= 50% LREM Analysis Set

PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab12.0
Platinum-based SoC10.9

[back to top]

Change From Baseline in EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set

The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. An outcome variable consisted of a score from 0 to 100. Higher scores on the global health status and functioning scales indicate better health status/function, but higher scores on symptom scales/items represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-C30 considered all data from baseline to PD or 12 months. (NCT03003962)
Timeframe: Baseline and 12 months

,
Interventionscores on a scale (Mean)
Global health statusPhysical functioningFatigueAppetite loss
Durvalumab-1.4-3.92.2-0.2
Platinum-based SoC-7.3-6.07.79.8

[back to top]

Change From Baseline in EORTC 13-Item Lung Cancer Quality of Life Questionnaire (QLQ-LC13)

The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months. (NCT03003962)
Timeframe: Baseline and 12 months

,
Interventionscores on a scale (Mean)
CoughDyspneaChest pain
Durvalumab-6.42.4-1.0
Platinum-based SoC-7.94.1-0.2

[back to top]

Percentage of Participants With Antidrug Antibody (ADA) Response to Durvalumab

Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. (NCT03003962)
Timeframe: Up to 24 weeks

Interventionpercentage of participants (Number)
Treatment-emergent ADA positiveTreatment-boosted ADAPersistently positiveTransiently positive
Durvalumab0.80.400.8

[back to top]

Time From Randomization to Second Progression (PFS2)

PFS2 was defined as the time from the date of randomization to the earliest of the progression events defined according to local clinical practice (subsequent to that used for the primary variable PFS) or death (i.e., date of PFS2 event or censoring - date of randomization + 1). PFS2 was calculated using the Kaplan-Meier technique. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) until confirmed objective disease progression. Disease then assessed as per local practice until 2nd progression or death (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab11.3
Platinum-based SoC9.3

[back to top]

OS at 24 Months in PD-L1 TC >= 50% Analysis Set

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months. (NCT03003962)
Timeframe: From date of randomization till 24 months

Interventionpercentage of participants (Number)
Durvalumab37.0
Platinum-based SoC27.0

[back to top]

Progression Free Survival (PFS) Based on Investigator Assessment According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

The PFS (per RECIST 1.1) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). Progression of disease per RECIST 1.1, when either 1 of the criteria met: Target lesion (TL): at least a 20% increase in the sum of diameters of TLs, for reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Non-target lesion (NTL): Unequivocal progression of existing NTLs. It may be due to an important progression in 1 lesion only or in several lesions. In all cases the progression must be clinically significant for the physician to consider changing (or stopping) therapy. New lesions: the presence of 1 or more new lesions was assessed as progression. (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months DCO 27 October 2022)

Interventionmonths (Median)
Durvalumab5.4
Platinum-based SoC4.8

[back to top]

OS at 24 Months in PD-L1 TC >= 50% LREM Analysis Set

OS was defined as the time from the date of randomization until death due to any cause. Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The percentage of participants alive at 24 months were defined as the Kaplan-Meier estimate of OS at 24 months. (NCT03003962)
Timeframe: From date of randomization till 24 months

Interventionpercentage of participants (Number)
Durvalumab36.9
Platinum-based SoC32.6

[back to top]

OS in Participants With LREM

OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. (NCT03003962)
Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Interventionmonths (Median)
Durvalumab14.6
Platinum-based SoC15.0

[back to top]

OS in PD-L1 TC >= 50% Analysis Set

OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. (NCT03003962)
Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Interventionmonths (Median)
Durvalumab14.6
Platinum-based SoC11.8

[back to top]

OS in PD-L1 TC >= 50% LREM Analysis Set

OS is defined as the time from the date of randomization until death due to ay cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. (NCT03003962)
Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

Interventionmonths (Median)
Durvalumab14.9
Platinum-based SoC14.9

[back to top]

Overall Survival (OS)

OS is defined as the time from the date of randomization until death due to any cause (date of death or censoring-date of randomization + 1). Any participant not known to have died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. (NCT03003962)
Timeframe: From date of randomization until death due to any cause. Assessed up to a maximum of approximately 69 months [data cut-off (DCO) 27 October 2022]

Interventionmonths (Median)
Durvalumab14.6
Platinum-based SoC12.8

[back to top]

PFS Based on Investigator Assessment According to RECIST 1.1 in LREM Analysis Set

The PFS (per RECIST 1.1 using Investigator assessments) was defined as the time from the date of randomization until the date of objective disease progression or death regardless of whether the participants withdrew from randomized therapy or received another anticancer therapy prior to progression (i.e., date of PFS event or censoring - date of randomization +1). (NCT03003962)
Timeframe: Tumor assessments (per RECIST 1.1) every 6 weeks for the first 48 weeks relative to the date of randomization and then every 8 weeks thereafter until confirmed objective disease progression (up to a maximum of approximately 69 months)

Interventionmonths (Median)
Durvalumab5.5
Platinum-based SoC5.6

[back to top]

Percentage of Participants With ADA Response to Durvalumab in LREM Analysis Set

Treatment-emergent ADA positive was defined as either treatment-induced or treatment-boosted ADA. Treatment-boosted ADA was defined as a baseline positive ADA titer that was boosted to a 4-fold or higher-level following study drug administration. Persistently positive was defined as positive at least 2 post-baseline assessments with at least 16 weeks between the first and last positive assessment or positive at last post-baseline assessment. Transiently positive was defined as having at least 1 post-baseline ADA positive assessment and not fulfilling the conditions of persistently positive. (NCT03003962)
Timeframe: Up to 24 weeks

Interventionpercentage of participants (Number)
Treatment-emergent ADA positiveTreatment-boosted ADAPersistently positiveTransiently positive
Durvalumab1.00.501.0

[back to top]

Time to Deterioration of EORTC QLQ-C30

Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration (a decrease in the function scales or the global health status/ health-related quality of life [HRQoL] from baseline of ≥10) that was confirmed at a subsequent visit or death in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. (NCT03003962)
Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

,
Interventionmonths (Median)
Global health statusPhysical functioningAppetite lossFatigue
Durvalumab7.37.49.24.9
Platinum-based SoC3.83.83.61.8

[back to top]

Time to Deterioration of EORTC QLQ-C30 in PD-L1 TC >= 25% LREM Analysis Set

Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The EORTC QLQ-C30 consisted of 30 questions that were combined to produce 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea/vomiting), 5 individual items (dyspnea, insomnia, appetite loss, constipation, and diarrhea), and a global measure of health status. The EORTC QLQ-C30 was scored according to the EORTC QLQ-C30 scoring manual. (NCT03003962)
Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to a maximum of approximately 69 months (DCO 27 October 2022)

,
Interventionmonths (Median)
Global health statusPhysical functioningAppetite lossFatigue
Durvalumab7.47.49.35.5
Platinum-based SoC5.54.73.71.8

[back to top]

Time to Deterioration of EORTC QLQ-LC13

Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. (NCT03003962)
Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)

,
Interventionmonths (Median)
CoughDyspneaChest pain
Durvalumab7.52.89.0
Platinum-based SoC6.63.66.4

[back to top]

Change From Baseline in EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set

The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. An outcome variable consisted of a score from 0 to 100. Higher scores on symptom scales represent greater symptom severity. Baseline was defined as the last non-missing assessment prior to randomization. The MMRM analysis of EORTC QLQ-LC13 considered all data from baseline to PD or 12 months. (NCT03003962)
Timeframe: Baseline and 12 months

,
Interventionscores on a scale (Mean)
CoughDyspneaChest pain
Durvalumab-6.62.9-0.7
Platinum-based SoC-8.63.9-1.0

[back to top]

Time to Deterioration of EORTC QLQ-LC13 in PD-L1 TC >= 25% LREM Analysis Set

Time to symptom deterioration was defined as the time from the date of randomization until the date if the first clinically meaningful symptom deterioration a decrease in the function scales or the global health status/ HRQoL from baseline of ≥10) that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful symptom deterioration, regardless of whether the participant withdraws from the study treatment or received another anticancer therapy prior to symptom deterioration. The QLQ-LC13 is a lung cancer specific module from the EORTC for lung cancer that comprised of 13 questions to assess lung cancer symptoms (cough, hemoptysis, dyspnea, and site-specific pain), treatment-related side-effects (sore mouth, dysphagia, peripheral neuropathy, and alopecia), and pain medication. (NCT03003962)
Timeframe: From randomization until date of first symptom deterioration that is confirmed, assessed up to maximum of approximately 69 months (DCO 27 October 2022)

,
Interventionmonths (Median)
CoughDyspneaChest pain
Durvalumab9.23.69.8
Platinum-based SoC8.23.66.6

[back to top]

Count of Adverse Events Evaluated by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.

"The safety evaluation of the population included all patients who received at least one dose of study medication. The descriptions and grading scales found in the revised NCI CTCAE version 4.0 will be utilized for adverse event reporting where Grade refers to the severity of the AE.~The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline:~Grade 1 Mild; asymptomatic or mild symptoms Grade 2 Moderate; minimal Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care of activity of daily living Grade 4 Life-threatening consequences; urgent intervention indicated Grade 5 Death related to AE" (NCT03029598)
Timeframe: Up to 3.5 years

Interventionadverse events (Number)
Grade 1 - Total Number of Reported AEsGrade 2 - Total Number of Reported AEsGrade 3 - Total Number of Reported AEsGrade 4 - Total Number of Reported AEs
Treatment (Pembrolizumab, Carboplatin)597169402

[back to top] [back to top] [back to top]

Number of Participants That Were PD-L1 Positive Based On PD-L1 Expression of Primary Tumor Blocks Assessed by Immunohistochemical Staining

PD-L1 antibody-stained archival tumor was evaluated by a board-certified pathologist and given a modified proportion score (MPS), or the overall percent of positive cells expressing PD-L1, and a MPS ≥ 5% was defined as PD-L1 positive. (NCT03029598)
Timeframe: Up to 3.5 years

InterventionParticipants (Count of Participants)
Treatment (Pembrolizumab, Carboplatin)7

[back to top]

Overall Survival (OS)

Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control OS will be conducted by examining whether the 95% confidence internal covers the historical control proportions. (NCT03029598)
Timeframe: Up to 3.5 years

Interventionmonths (Median)
Treatment (Pembrolizumab, Carboplatin)11.3

[back to top]

Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

"Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% CIs at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.~Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm." (NCT03029598)
Timeframe: Up to 3.5 years

Interventionmonths (Median)
Treatment (Pembrolizumab, Carboplatin)4.63

[back to top]

Response Rate (RR) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI/CT scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT03029598)
Timeframe: 6 months

InterventionParticipants (Count of Participants)
Patients that achieved a Partial Response (PR)Patient achieved Stable Disease (SD)Patients that had Progressive Disease (PD)
Treatment (Pembrolizumab, Carboplatin)3155

[back to top]

Progression-free Survival (PFS) Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

"Analyzed using the Kaplan-Meier method. Kaplan-Meier estimates of the survival function with 95% confidence intervals (CIs) at specific time points (using Greenwood's formula for the standard error) were computed. Comparisons with the historical control PFS will be conducted by examining whether the 95% confidence internal covers the historical control proportions.~Progression-free survival (PFS) is defined as the length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse. Participants are evaluated by RECIST1.1 to determine if/when a participant's disease has progressed defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm." (NCT03029598)
Timeframe: 6 months

Interventionmonths (Median)
Treatment (Pembrolizumab, Carboplatin)4.63

[back to top]

Best Overall Response (BOR)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI/CT scans: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR (NCT03029598)
Timeframe: Up to 3.5 years

InterventionParticipants (Count of Participants)
Partial ResponseStable DiseaseProgressive Disease
Treatment (Pembrolizumab, Carboplatin)3155

[back to top]

Rate of Pathologic Complete Response (CR)

The tissue collected at time of cytoreductive surgery, post study treatment, was evaluated by the attending pathologist assigned to look at the tissue for viable tumor cells. The corresponding surgical pathology report was reviewed to evaluate individual pCR (absence of viable tumor cells). (NCT03029611)
Timeframe: At the time of cytoreductive surgery after receiving study treatment (vaccinations given intradermally approximately two weeks after each combination chemotherapy for 3 doses.)

InterventionParticipants (Count of Participants)
Treatment (Chemotherapy, IGFBP-2 Vaccine)0

[back to top]

Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group in ITT Population

DOR is defined as the time interval from first occurrence of a CR or PR to the time of disease progression, as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever comes first for patients with measurable residual disease after primary surgery. (NCT03038100)
Timeframe: From the date of first occurrence of a confirmed complete or partial response until disease progression or death from any cause (up to approximately 55 months)

InterventionMonths (Median)
Placebo With Paclitaxel, Carboplatin and Bevacizumab14.06
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab16.59

[back to top]

Duration of Response Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery (Having Residual Measurable Disease) Group in PD-L1-Positive Population

DOR is defined as the time interval from first occurrence of a CR or PR to the time of disease progression, as determined by the investigator with the use of RECIST v1.1, or death from any cause, whichever comes first for patients with measurable residual disease after primary surgery. (NCT03038100)
Timeframe: From the date of first occurrence of a confirmed complete or partial response until disease progression or death from any cause (up to approximately 55 months)

InterventionMonths (Median)
Placebo With Paclitaxel, Carboplatin and Bevacizumab13.44
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab17.71

[back to top]

Overall Survival - ITT Population

Overall Survival (OS) is defined as the time from randomization to death from any cause. (NCT03038100)
Timeframe: From randomization up to death from any cause (up to approximately 59 months)

InterventionMonths (Median)
Placebo With Paclitaxel, Carboplatin and Bevacizumab46.59
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab50.53

[back to top]

Overall Survival - PD-L1-Positive Subpopulation

Overall Survival (OS) is defined as the time from randomization to death from any cause. (NCT03038100)
Timeframe: From randomization up to death from any cause (up to approximately 59 months)

InterventionMonths (Median)
Placebo With Paclitaxel, Carboplatin and Bevacizumab49.15
Atezolizumab With Paclitaxel, Carboplatin and BevacizumabNA

[back to top]

Percentage of Participants With Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery Group in PD-L1-Positive Population

OR is defined as either a CR or PR as determined by the investigator with the use of RECIST v1.1 for patients with measurable residual disease after primary surgery. (NCT03038100)
Timeframe: From randomization until disease progression or death from any cause (up to approximately 55 months)

InterventionPercentage of participants (Number)
Placebo With Paclitaxel, Carboplatin and Bevacizumab89.9
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab92.3

[back to top]

Percentage of Participants With at Least One Adverse Event

Percentage of participants with at least one adverse event. (NCT03038100)
Timeframe: From randomization up to approximately 59 months

InterventionPercentage (Number)
Placebo With Paclitaxel, Carboplatin and Bevacizumab99.8
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab100

[back to top]

Progression-Free Survival (PFS) Assessed by Investigator as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) - Intent-to-Treat (ITT) Population

Investigator-assessed PFS is defined as the time from randomization to the occurrence of disease progression, as determined by the investigator from tumor assessments per RECIST v1.1, or death from any cause during the study, whichever occurs first. (NCT03038100)
Timeframe: From randomization until disease progression or death from any cause (up to approximately 55 months)

InterventionMonths (Median)
Placebo With Paclitaxel, Carboplatin and Bevacizumab18.37
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab19.48

[back to top]

Maximum Serum Concentration (Cmax) of Atezolizumab

(NCT03038100)
Timeframe: Cycle 1 Day 1 post dose and Cycle 3 Day 1 post dose

Interventionµg/mL (Mean)
Cycle 1 Day 1Cycle 3 Day 1
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab487614

[back to top]

Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab

(NCT03038100)
Timeframe: Baseline to approximately 55 months

InterventionPercentage of participants (Number)
Baseline evaluable participantsPost-baseline evaluable participants
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab0.722.7

[back to top]

PFS Assessed by Investigator as Per RECIST v1.1 - Programmed Death-Ligand 1 (PD-L1)-Positive Subpopulation

Investigator-assessed PFS is defined as the time from randomization to the occurrence of disease progression, as determined by the investigator from tumor assessments per RECIST v1.1, or death from any cause during the study, whichever occurs first. (NCT03038100)
Timeframe: From randomization until disease progression or death from any cause (up to approximately 55 months)

InterventionMonths (Median)
Placebo With Paclitaxel, Carboplatin and Bevacizumab18.50
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab20.83

[back to top]

Percentage of Participants With Deterioration in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group

Percentage of participants with deterioration in patient-reported function and HRQoL, defined as >= 10 points decrease from the baseline score on each of the functional (physical, role, emotional, and social) and GHS/QoL scales of the EORTC QLQ-C30. (NCT03038100)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 60 months). Cycle length=21 days.

,
InterventionPercentage of participants (Number)
Physical Functioning, Cycle 3 Day 1Physical Functioning, Cycle 5 Day 1Physical Functioning, Cycle 8 Day 1Physical Functioning, Cycle 12 Day 1Physical Functioning, Cycle 16 Day 1Physical Functioning, Cycle 20 Day 1Physical Functioning, Completion of Treatment/ Early Termination VisitPhysical Functioning, Post-Treatment Follow Up 3 MonthsPhysical Functioning, Post-Treatment Follow Up 6 MonthsPhysical Functioning, Post-Treatment Follow Up 9 MonthsPhysical Functioning, Post-Treatment Follow Up 12 MonthsPhysical Functioning, Post-Treatment Follow Up 18 MonthsPhysical Functioning, Post-Treatment Follow Up 24 MonthsRole Functioning, Cycle 3 Day 1Role Functioning, Cycle 5 Day 1Role Functioning, Cycle 8 Day 1Role Functioning, Cycle 12 Day 1Role Functioning, Cycle 16 Day 1Role Functioning, Cycle 20 Day 1Role Functioning, Completion of Treatment/ Early Termination VisitRole Functioning, Post-Treatment Follow Up 3 MonthsRole Functioning, Post-Treatment Follow Up 6 MonthsRole Functioning, Post-Treatment Follow Up 9 MonthsRole Functioning, Post-Treatment Follow Up 12 MonthsRole Functioning, Post-Treatment Follow Up 18 MonthsRole Functioning, Post-Treatment Follow Up 24 MonthsSocial Functioning, Cycle 3 Day 1Social Functioning, Cycle 5 Day 1Social Functioning, Cycle 8 Day 1Social Functioning, Cycle 12 Day 1Social Functioning, Cycle 16 Day 1Social Functioning, Cycle 20 Day 1Social Functioning, Completion of Treatment/ Early Termination VisitSocial Functioning, Post-Treatment Follow Up 3 MonthsSocial Functioning, Post-Treatment Follow Up 6 MonthsSocial Functioning, Post-Treatment Follow Up 9 MonthsSocial Functioning, Post-Treatment Follow Up 12 MonthsSocial Functioning, Post-Treatment Follow Up 18 MonthsSocial Functioning, Post-Treatment Follow Up 24 MonthsEmotional Functioning, Cycle 3 Day 1Emotional Functioning, Cycle 5 Day 1Emotional Functioning, Cycle 8 Day 1Emotional Functioning, Cycle 12 Day 1Emotional Functioning, Cycle 16 Day 1Emotional Functioning, Cycle 20 Day 1Emotional Functioning, Completion of Treatment/ Early Termination VisitEmotional Functioning, Post-Treatment Follow Up 3 MonthsEmotional Functioning, Post-Treatment Follow Up 6 MonthsEmotional Functioning, Post-Treatment Follow Up 9 MonthsEmotional Functioning, Post-Treatment Follow Up 12 MonthsEmotional Functioning, Post-Treatment Follow Up 18 MonthsEmotional Functioning, Post-Treatment Follow Up 24 MonthsGHS/OoL Function, Cycle 3 Day 1GHS/OoL Function, Cycle 5 Day 1GHS/OoL Function, Cycle 8 Day 1GHS/OoL Function, Cycle 12 Day 1GHS/OoL Function, Cycle 16 Day 1GHS/OoL Function, Cycle 20 Day 1GHS/OoL Function, Completion of Treatment/ Early Termination VisitGHS/OoL Function, Post-Treatment Follow Up 3 MonthsGHS/OoL Function, Post-Treatment Follow Up 6 MonthsGHS/OoL Function, Post-Treatment Follow Up 9 MonthsGHS/OoL Function, Post-Treatment Follow Up 12 MonthsGHS/OoL Function, Post-Treatment Follow Up 18 MonthsGHS/OoL Function, Post-Treatment Follow Up 24 Months
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab24.128.623.616.517.016.725.123.725.025.525.925.05027.827.022.716.815.813.324.327.125.626.537.931.316.731.230.625.819.017.616.228.125.430.532.737.937.533.314.015.912.413.412.511.119.316.914.618.422.431.366.722.823.718.113.213.511.124.322.923.825.534.543.850.0
Placebo With Paclitaxel, Carboplatin and Bevacizumab24.127.123.417.217.118.220.522.624.519.017.821.4021.326.721.116.720.118.623.020.920.419.06.77.1029.029.621.818.919.520.227.226.523.022.68.914.3012.817.314.612.213.215.519.319.720.98.38.97.1024.224.121.317.618.320.224.520.520.921.417.821.40

[back to top]

Percentage of Participants With Objective Response (OR) Assessed by Investigator as Per RECIST v1.1 - Primary Tumor-Reductive Surgery Group in ITT Population

OR is defined as either a CR or PR as determined by the investigator with the use of RECIST v1.1 for patients with measurable residual disease after primary surgery. (NCT03038100)
Timeframe: From randomization until disease progression or death from any cause (up to approximately 55 months)

InterventionPercentage of participants (Number)
Placebo With Paclitaxel, Carboplatin and Bevacizumab88.7
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab92.8

[back to top]

Percentage of Participants Who Remain Stable in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group

Percentage of participants who remain stable defined as changes within 10 points from the baseline score on each of the functional (physical, role, emotional, and social) and GHS/QoL scales of the EORTC QLQ-C30. (NCT03038100)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days.

,
InterventionPercentage of participants (Number)
Physical Functioning, Cycle 3 Day 1Physical Functioning, Cycle 5 Day 1Physical Functioning, Cycle 8 Day 1Physical Functioning, Cycle 12 Day 1Physical Functioning, Cycle 16 Day 1Physical Functioning, Cycle 20 Day 1Physical Functioning, Completion of Treatment/ Early Termination VisitPhysical Functioning, Post-Treatment Follow Up 3 MonthsPhysical Functioning, Post-Treatment Follow Up 6 MonthsPhysical Functioning, Post-Treatment Follow Up 9 MonthsPhysical Functioning, Post-Treatment Follow Up 12 MonthsPhysical Functioning, Post-Treatment Follow Up 18 MonthsPhysical Functioning, Post-Treatment Follow Up 24 MonthsRole Functioning, Cycle 3 Day 1Role Functioning, Cycle 5 Day 1Role Functioning, Cycle 8 Day 1Role Functioning, Cycle 12 Day 1Role Functioning, Cycle 16 Day 1Role Functioning, Cycle 20 Day 1Role Functioning, Completion of Treatment/ Early Termination VisitRole Functioning, Post-Treatment Follow Up 3 MonthsRole Functioning, Post-Treatment Follow Up 6 MonthsRole Functioning, Post-Treatment Follow Up 9 MonthsRole Functioning, Post-Treatment Follow Up 12 MonthsRole Functioning, Post-Treatment Follow Up 18 MonthsRole Functioning, Post-Treatment Follow Up 24 MonthsSocial Functioning, Cycle 3 Day 1Social Functioning, Cycle 5 Day 1Social Functioning, Cycle 8 Day 1Social Functioning, Cycle 12 Day 1Social Functioning, Cycle 16 Day 1Social Functioning, Cycle 20 Day 1Social Functioning, Completion of Treatment/ Early Termination VisitSocial Functioning, Post-Treatment Follow Up 3 MonthsSocial Functioning, Post-Treatment Follow Up 6 MonthsSocial Functioning, Post-Treatment Follow Up 9 MonthsSocial Functioning, Post-Treatment Follow Up 12 MonthsSocial Functioning, Post-Treatment Follow Up 18 MonthsSocial Functioning, Post-Treatment Follow Up 24 MonthsEmotional Functioning, Cycle 3 Day 1Emotional Functioning, Cycle 5 Day 1Emotional Functioning, Cycle 8 Day 1Emotional Functioning, Cycle 12 Day 1Emotional Functioning, Cycle 16 Day 1Emotional Functioning, Cycle 20 Day 1Emotional Functioning, Completion of Treatment/ Early Termination VisitEmotional Functioning, Post-Treatment Follow Up 3 MonthsEmotional Functioning, Post-Treatment Follow Up 6 MonthsEmotional Functioning, Post-Treatment Follow Up 9 MonthsEmotional Functioning, Post-Treatment Follow Up 12 MonthsEmotional Functioning, Post-Treatment Follow Up 18 MonthsEmotional Functioning, Post-Treatment Follow Up 24 MonthsGHS/OoL, Cycle 3 Day 1GHS/OoL, Cycle 5 Day 1GHS/OoL, Cycle 8 Day 1GHS/OoL, Cycle 12 Day 1GHS/OoL, Cycle 16 Day 1GHS/OoL, Cycle 20 Day 1GHS/OoL, Completion of Treatment/ Early Termination VisitGHS/OoL, Post-Treatment Follow Up 3 MonthsGHS/OoL, Post-Treatment Follow Up 6 MonthsGHS/OoL, Post-Treatment Follow Up 9 MonthsGHS/OoL, Post-Treatment Follow Up 12 MonthsGHS/OoL, Post-Treatment Follow Up 18 MonthsGHS/OoL, Post-Treatment Follow Up 24 Months
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab56.150.149.451.148.750.944.547.943.946.950.056.333.330.933.630.932.133.434.828.627.129.934.734.525.066.736.736.735.239.233.333.831.132.634.830.625.918.816.757.353.654.650.151.352.151.855.547.648.043.137.516.742.244.842.942.943.342.340.338.642.138.832.837.516.7
Placebo With Paclitaxel, Carboplatin and Bevacizumab53.149.047.847.150.546.646.841.342.246.444.435.710035.830.131.232.927.627.328.625.124.523.833.342.95040.737.640.238.336.634.131.930.333.827.428.928.6057.552.453.253.255.049.253.051.348.653.646.750.050.043.342.639.040.738.436.937.238.939.939.342.235.70

[back to top]

Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and HRQoL - Primary Tumor-Reductive Surgery Group

Percentage of participants with clinical improvement, defined as >= 10-point increase from the baseline score on each of the functional (physical, role, emotional, and social) and GHS/QoL scales of the EORTC QLQ-C30. (NCT03038100)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days.

,
InterventionPercentage of participants (Number)
Physical Functioning, Cycle 3 Day 1Physical Functioning, Cycle 5 Day 1Physical Functioning, Cycle 8 Day 1Physical Functioning, Cycle 12 Day 1Physical Functioning, Cycle 16 Day 1Physical Functioning, Cycle 20 Day 1Physical Functioning, Completion of Treatment/Early Termination VisitPhysical Functioning, Post-Treatment Follow Up 3 MonthsPhysical Functioning, Post-Treatment Follow Up 6 MonthsPhysical Functioning, Post-Treatment Follow Up 9 MonthsPhysical Functioning, Post-Treatment Follow Up 12 MonthsPhysical Functioning, Post-Treatment Follow Up 18 MonthsPhysical Functioning, Post-Treatment Follow Up 24 MonthsRole Functioning, Cycle 3 Day 1Role Functioning, Cycle 5 Day 1Role Functioning, Cycle 8 Day 1Role Functioning, Cycle 12 Day 1Role Functioning, Cycle 16 Day 1Role Functioning, Cycle 20 Day 1Role Functioning, Completion of Treatment/ Early Termination VisitRole Functioning, Post-Treatment Follow Up 3 MonthsRole Functioning, Post-Treatment Follow Up 6 MonthsRole Functioning, Post-Treatment Follow Up 9 MonthsRole Functioning, Post-Treatment Follow Up 12 MonthsRole Functioning, Post-Treatment Follow Up 18 MonthsRole Functioning, Post-Treatment Follow Up 24 MonthsSocial Functioning, Cycle 3 Day 1Social Functioning, Cycle 5 Day 1Social Functioning, Cycle 8 Day 1Social Functioning, Cycle 12 Day 1Social Functioning, Cycle 16 Day 1Social Functioning, Cycle 20 Day 1Social Functioning, Completion of Treatment/ Early Termination VisitSocial Functioning, Post-Treatment Follow Up 3 MonthsSocial Functioning, Post-Treatment Follow Up 6 MonthsSocial Functioning, Post-Treatment Follow Up 9 MonthsSocial Functioning, Post-Treatment Follow Up 12 MonthsSocial Functioning, Post-Treatment Follow Up 18 MonthsSocial Functioning, Post-Treatment Follow Up 24 MonthsEmotional Functioning, Cycle 3 Day 1Emotional Functioning, Cycle 5 Day 1Emotional Functioning, Cycle 8 Day 1Emotional Functioning, Cycle 12 Day 1Emotional Functioning, Cycle 16 Day 1Emotional Functioning, Cycle 20 Day 1Emotional Functioning, Completion of Treatment/ Early Termination VisitEmotional Functioning, Post-Treatment Follow Up 3 MonthsEmotional Functioning, Post-Treatment Follow Up 6 MonthsEmotional Functioning, Post-Treatment Follow Up 9 MonthsEmotional Functioning, Post-Treatment Follow Up 12 MonthsEmotional Functioning, Post-Treatment Follow Up 18 MonthsEmotional Functioning, Post-Treatment Follow Up 24 MonthsGHS/OoL, Cycle 3 Day 1GHS/OoL, Cycle 5 Day 1GHS/OoL, Cycle 8 Day 1GHS/OoL, Cycle 12 Day 1GHS/OoL, Cycle 16 Day 1GHS/OoL, Cycle 20 Day 1GHS/OoL, Completion of Treatment/ Early Termination VisitGHS/OoL, Post-Treatment Follow Up 3 MonthsGHS/OoL, Post-Treatment Follow Up 6 MonthsGHS/OoL, Post-Treatment Follow Up 9 MonthsGHS/OoL, Post-Treatment Follow Up 12 MonthsGHS/OoL, Post-Treatment Follow Up 18 MonthsGHS/OoL, Post-Treatment Follow Up 24 Months
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab19.821.327.032.434.332.530.328.431.127.624.118.816.740.938.945.950.650.851.546.645.343.938.827.643.816.731.432.038.741.248.750.040.141.134.136.736.243.850.028.430.333.036.135.936.828.627.537.833.734.531.316.734.531.038.743.442.946.234.938.634.135.732.818.833.3
Placebo With Paclitaxel, Carboplatin and Bevacizumab22.623.728.735.432.134.832.435.732.734.537.842.9042.642.947.550.152.053.848.454.055.157.160505030.132.637.842.643.545.640.642.743.250.062.257.110029.730.332.334.631.835.327.729.130.438.144.442.950.032.333.039.541.542.942.538.040.639.239.340.042.9100

[back to top]

Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Function and Health Related Quality of Life (HRQoL) - Neoadjuvant Group

Clinically-meaningful improvement in patient-reported function and HRQoL during the treatment period, defined as a >=10-point increase from the baseline score on each of the functional (social, emotional, physical, role) and GHS/QoLscales of the European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires Core 30 (EORTC QLQ-C30). (NCT03038100)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days.

,
InterventionPercentage of participants (Number)
Physical Functioning, Presurgical/SurgeryPhysical Functioning, Cycle 4 Day 1Physical Functioning, Cycle 6 Day 1Physical Functioning, Cycle 8 Day 1Physical Functioning, Cycle 12 Day 1Physical Functioning, Cycle 16 Day 1Physical Functioning, Cycle 20 Day 1Physical Functioning, Completion of Treatment/Early Termination VisitPhysical Functioning, Post-Treatment Follow Up 3 MonthsPhysical Functioning, Post-Treatment Follow Up 6 MonthsPhysical Functioning, Post-Treatment Follow Up 9 MonthsPhysical Functioning, Post-Treatment Follow Up 12 MonthsPhysical Functioning, Post-Treatment Follow Up 18 MonthsPhysical Functioning, Post-Treatment Follow Up 24 MonthsRole Functioning, Presurgical/SurgeryRole Functioning, Cycle 4 Day 1Role Functioning, Cycle 6 Day 1Role Functioning, Cycle 8 Day 1Role Functioning, Cycle 12 Day 1Role Functioning, Cycle 16 Day 1Role Functioning, Cycle 20 Day 1Role Functioning, Completion of Treatment/ Early Termination VisitRole Functioning, Post-Treatment Follow Up 3 MonthsRole Functioning, Post-Treatment Follow Up 6 MonthsRole Functioning, Post-Treatment Follow Up 9 MonthsRole Functioning, Post-Treatment Follow Up 12 MonthsRole Functioning, Post-Treatment Follow Up 18 MonthsRole Functioning, Post-Treatment Follow Up 24 MonthsSocial Functioning, Presurgical/SurgerySocial Functioning, Cycle 4 Day 1Social Functioning, Cycle 6 Day 1Social Functioning, Cycle 8 Day 1Social Functioning, Cycle 12 Day 1Social Functioning, Cycle 16 Day 1Social Functioning, Cycle 20 Day 1Social Functioning, Completion of Treatment/Early TerminationSocial Functioning, Post-Treatment Follow Up 3 MonthsSocial Functioning, Post-Treatment Follow Up 6 MonthsSocial Functioning, Post-Treatment Follow Up 9 MonthsSocial Functioning, Post-Treatment Follow Up 12 MonthsSocial Functioning, Post-Treatment Follow Up 18 MonthsSocial Functioning, Post-Treatment Follow Up 24 MonthsEmotional Functioning, Presurgical/SurgeryEmotional Functioning, Cycle 4 Day 1Emotional Functioning, Cycle 6 Day 1Emotional Functioning, Cycle 8 Day 1Emotional Functioning, Cycle 12 Day 1Emotional Functioning, Cycle 16 Day 1Emotional Functioning, Cycle 20 Day 1Emotional Functioning, Completion of Treatment/Early Termination VisitEmotional Functioning, Post-Treatment Follow Up 3 monthsEmotional Functioning, Post-Treatment Follow Up 6 monthsEmotional Functioning, Post-Treatment Follow Up 9 monthsEmotional Functioning, Post-Treatment Follow Up 12 monthsEmotional Functioning, Post-Treatment Follow Up 18 monthsEmotional Functioning, Post-Treatment Follow Up 24 monthsGHS/HRQoL, PresurgicalSurgeryGHS/HRQoL, Cycle 4 Day 1GHS/HRQoL, Cycle 6 Day 1GHS/HRQoL, Cycle 8 Day 1GHS/HRQoL, Cycle 12 Day 1GHS/HRQoL, Cycle 16 Day 1GHS/HRQoL, Cycle 20 Day 1GHS/HRQoL, Completion of Treatment/ Early Termination VisitGHS/HRQoL, Post-Treatment Follow Up 3 MonthsGHS/HRQoL, Post-Treatment Follow Up 6 MonthsGHS/HRQoL, Post-Treatment Follow Up 9 MonthsGHS/HRQoL, Post-Treatment Follow Up 12 MonthsGHS/HRQoL, Post-Treatment Follow Up 18 MonthsGHS/HRQoL, Post-Treatment Follow Up 24 Months
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab33.618.025.636.643.142.031.734.439.239.250.037.550.050.040.922.633.639.847.146.652.439.740.248.652.654.250.050.033.625.633.339.344.644.343.541.544.835.147.454.275.050.030.735.638.244.741.642.032.333.833.333.834.229.250.050.046.737.147.759.061.458.061.353.153.141.950.041.750.050.0
Placebo With Paclitaxel, Carboplatin and Bevacizumab35.928.435.637.245.942.741.038.937.140.832.623.533.310048.638.345.950.455.953.156.646.949.551.353.523.550.0032.431.236.840.339.640.045.840.342.746.146.529.466.7031.731.242.139.541.444.844.633.835.430.339.529.416.7044.443.351.155.060.453.159.046.953.748.739.517.616.70

[back to top]

Percentage of Participants Who Achieve a Clinically-Meaningful Improvement in Patient-Reported Abdominal Pain and Bloating - Neoadjuvant Group

Clinically-meaningful improvement defined as a >=10-point decrease from the baseline score in patient-reported abdominal pain or bloating will be assessed using European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaires Ovarian Cancer Module 28 (EORTC QLQ-OV28) Abdominal/Gastrointestinal Symptom Scale (Items 31 and 31). (NCT03038100)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 66 weeks), and during follow-up period (up to approximately 55 months). Cycle length=21 days.

,
InterventionPercentage of participants (Number)
Abdominal Pain, Presurgical/SurgeryAbdominal Pain, Cycle 4 Day 1Abdominal Pain, Cycle 6 Day 1Abdominal Pain, Cycle 8 Day 1Abdominal Pain, Cycle 12 Day 1Abdominal Pain, Cycle 16 Day 1Abdominal Pain, Cycle 20 Day 1Abdominal Pain, Completion of Treatment/Early Termination VisitAbdominal Pain, Post-Treatment Follow Up 3 MonthsAbdominal Pain, Post-Treatment Follow Up 6 MonthsAbdominal Pain, Post-Treatment Follow Up 9 MonthsAbdominal Pain, Post-Treatment Follow Up 12 MonthsAbdominal Pain, Post-Treatment Follow Up 18 MonthsAbdominal Pain, Post-Treatment Follow Up 24 MonthsBloating, Presurgical/SurgeryBloating, Cycle 4 Day 1Bloating, Cycle 6 Day 1Bloating, Cycle 8 Day 1Bloating, Cycle 12 Day 1Bloating, Cycle 16 Day 1Bloating, Cycle 20 Day 1Bloating, Completion of Treatment/ Early Termination VisitBloating, Post-Treatment Follow Up 3 MonthsBloating, Post-Treatment Follow Up 6 MonthsBloating, Post-Treatment Follow Up 9 MonthsBloating, Post-Treatment Follow Up 12 MonthsBloating, Post-Treatment Follow Up 18 MonthsBloating, Post-Treatment Follow Up 24 Months
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab50.732.348.154.157.458.048.451.551.051.450.058.350.010054.059.866.963.463.464.856.558.553.162.263.262.550.0100
Placebo With Paclitaxel, Carboplatin and Bevacizumab54.236.455.064.363.163.568.751.058.361.360.570.610010062.765.071.071.968.566.766.362.157.359.267.447.166.70

[back to top]

Minimum Serum Concentration (Cmin) of Atezolizumab

(NCT03038100)
Timeframe: Cycle 2 Day 1 predose, Cycle 3 Day 1 Predose, Cycle 4 Day 1 predose, Cycle 8 Day 1 predose, Cycle 16 Day 1 predose

Interventionµg/mL (Mean)
Cycle 2 Day 1Cycle 3 Day 1Cycle 4 Day 1Cycle 8 Day 1Cycle 16 Day 1
Atezolizumab With Paclitaxel, Carboplatin and Bevacizumab88.9146149242286

[back to top]

Number of Participants With at Least 1 Occurrence of Grade 3 or 4 Hematologic Laboratory Abnormalities

"The occurrence of Grade 3 and 4 hematologic toxicities was a binary endpoint. If a patient had at least 1 cycle with at least 1 Grade 3 or 4 hematologic toxicities during the Induction Period, the patient was assigned as Yes to the occurrence of Grade 3 and 4 hematologic toxicities; otherwise, it was No. If a patient did not have an event, the value of 0 was assigned to that patient." (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab23
Placebo+Etoposide/Carboplatin/Atezolizumab43

[back to top]

Number of Participants With at Least 1 Occurrence of Infection Serious Adverse Events (SAEs)

"Any occurrence of an infection SAE during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. The criterion for identifying the proper infection SAE records was as follows: if the system organ class (SOC) from Medical Dictionary for Regulatory Activities (MedDRA) Version 20.1 takes value INFECTIONS AND INFESTATIONS, and the AE was a serious event." (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab3
Placebo+Etoposide/Carboplatin/Atezolizumab7

[back to top]

Number of Participants With at Least 1 Occurrence of IV Antibiotic Uses

"Occurrence of an IV antibiotics administration during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of IV antibiotics administration ≥ 1 is observed, No for other scenarios. Each IV antibiotic with a unique start date during the induction treatment period will be defined as a separate event. The criteria for identifying an IV antibiotic administration event was (1) if the therapeutic subgroup from WHO-DD Version September 2017 (ie, TEXT2 for CODE2) takes the value ANTIBACTERIALS FOR SYSTEMIC USE, and (2) the route of medication was intravenous or the route was other with the detailed specification as IVPB." (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab10
Placebo+Etoposide/Carboplatin/Atezolizumab12

[back to top]

Number of Participants With at Least 1 Occurrence of Platelet Transfusion

Any occurrence of a platelet transfusion during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. Each platelet transfusion event with a unique start date during the induction treatment period was defined as a separate event. (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab1
Placebo+Etoposide/Carboplatin/Atezolizumab2

[back to top]

Number of Participants With at Least 1 Occurrence of Pulmonary Infection Serious Adverse Events (SAEs)

"Any occurrence of a pulmonary SAE during the induction treatment period was defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. If the patient did not have an event, the value of 0 was assigned to that patient. Each pulmonary infection SAE with a unique start date during the induction treatment period was defined as separate event. The criterion for identifying the proper pulmonary infection SAE records was as follows:~The SOC from MedDRA Version 20.1 took the value INFECTIONS AND INFESTATIONS, the adverse event was a serious event, and the PT took values from the following list of PTs under the category of pulmonary infection adverse events: bronchiolitis, bronchitis, infectious pleural effusion, influenza, pneumonia, pneumonia bacterial, respiratory tract infection, upper respiratory tract infection, and viral upper respiratory tract infection." (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab2
Placebo+Etoposide/Carboplatin/Atezolizumab5

[back to top]

Number of Participants With at Least 1 Occurrence of RBC Transfusion on/After Week 5 (Proportion of Patients)

For this endpoint, the occurrence during the Induction Period was defined as a binary variable (Yes or No); Yes, if total number of events ≥1 was observed, No for other scenarios. If a patient did not have an event, a value of 0 was assigned to that patient. Each red blood cell transfusion with a unique start date on/after Week 5 on study during the Induction was defined as a separate event. (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 374 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab7
Placebo+Etoposide/Carboplatin/Atezolizumab11

[back to top]

Occurrence of Granulocyte Colony-Stimulating Factor (G-CSF) Administration (Proportion of Patients)

For this endpoint, the occurrence during the Induction Period was defined as a binary variable (Yes or No); Yes, if total number of events ≥1 was observed, No for other scenarios. If a patient did not have an event, a value of 0 was assigned to that patient. Any G-CSF administration in a cycle during the Induction Period was defined as a separate event. A patient with at least 1 cycle with G-CSF administration during an induction cycle or the Induction Period was considered to have occurrence of G-CSF administration. (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab16
Placebo+Etoposide/Carboplatin/Atezolizumab25

[back to top]

Best Overall Response

For all patients, the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) tumor response data were used to determine each patient's visit response (TPR = time point response). Per RECIST v1.1 for target lesions and assessed by CT/MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameters of target lesions; Progressive Disease (PD), >=20% increase in the sum of the longest diameter of target lesions, Stable Disease, neither sufficient shrinkage or increase to quality for PR or PD. Objective Response Rate (ORR) = CR + PR. The TPR at each visit was determined in 2 ways: (1) derived programmatically at the time of analysis using the information from target lesions, non-target lesions, and new lesions based on data collected through eCRF; and (2) judged by the investigator as collected in the eCRF. Results shown here are from the programmatically derived assessments. (NCT03041311)
Timeframe: From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days.

,
InterventionParticipants (Count of Participants)
Complete Response (CR)Partial Response (PR)Stable Disease (SD)Progressive Disease (PD)Not Evaluable (NE)MissingObjective response rate (CR+PR)
Placebo+Etoposide/Carboplatin/Atezolizumab1321422133
Trilaciclib+Etoposide/Carboplatin/Atezolizumab0282020028

[back to top]

Duration of Objective Response (Complete Response or Partial Response)

Duration of Response (DOR) is the time between first response by RECIST Version 1.1 of CR or PR and the first date that progressive disease is documented by RECIST Version 1.1, or death. Patients who do not experience PD or death will be censored at the last tumor assessment date. Only those patients with confirmed responses will be included in this analysis. (NCT03041311)
Timeframe: From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days.

,
Interventionmonths (Number)
25%Median75%
Placebo+Etoposide/Carboplatin/Atezolizumab3.04.35.0
Trilaciclib+Etoposide/Carboplatin/Atezolizumab4.45.68.3

[back to top]

Duration of Study Drug Exposure (Induction Period and Maintenance Period)

Induction period duration of exposure (days) = Day 1 of last induction cycle - Cycle 1 Day 1 of induction phase + 21. Maintenance period duration of exposure (days) = Day 1 of the last maintenance cycle -Cycle 1 Day 1 of maintenance phase + 21. (NCT03041311)
Timeframe: From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days.

,
InterventionDays (Mean)
Induction PeriodMaintenance Period
Placebo+Etoposide/Carboplatin/Atezolizumab88232
Trilaciclib+Etoposide/Carboplatin/Atezolizumab83223

[back to top]

Major Adverse Hematologic Events (MAHE) (Composite Endpoint)

"The composite endpoint major adverse hematologic events (MAHE) included the following aspects of myelosuppression:~All-cause hospitalizations - Each recorded preferred term (PT) with a unique start date was counted as an event.~All-cause dose reductions - Dose reductions were permitted for E/P but not for trilaciclib or atezolizumab. No more than 2 dose reductions were allowed. Each dose reduction was counted as a separate event.~Febrile neutropenia-Each febrile neutropenia event with a unique start date during the Induction Period was defined as a separate event.~Prolonged severe neutropenia (SN)-Each cycle with a severe neutropenia duration greater than 5 days was counted as an event, with the date of the first Grade 4 laboratory value defined as the start date for the time-to-first event analysis.~Red blood cell (RBC) transfusion on/after Week 5-Each RBC transfusion with a unique start date on/after Week 5 on study during the Induction Period was defined as a separate event." (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

,
Interventionevent rate per week (Number)
Major adverse hematologic events (MAHE)All-cause hospitalizationsAll-cause dose reductionsFebrile neutropenia TEAEsRBC transfusions on/after Week 5Prolonged SN (>5 days)
Placebo+Etoposide/Carboplatin/Atezolizumab0.0580.0300.0850.0040.0260.170
Trilaciclib+Etoposide/Carboplatin/Atezolizumab0.1320.0320.0210.0020.0170.005

[back to top]

Number of Cycles Completed (Induction Period and Maintenance Period)

Patients were considered to have started a cycle if they have received at least one dose of any study drug (carboplatin, etoposide, atezolizumab or trilaciclib). (NCT03041311)
Timeframe: From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 49 cycles.

,
InterventionCycles (Mean)
Induction PeriodMaintenance Period
Placebo+Etoposide/Carboplatin/Atezolizumab410
Trilaciclib+Etoposide/Carboplatin/Atezolizumab410

[back to top]

Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Induction Period)

"After Cycle 1, patients need to meet pre-specified laboratory parameter criteria before initiating Cycle 2 and each subsequent cycle of chemotherapy. A Cycle Day Status page asks if the cycle was delayed. If the start of the current cycle was delayed (the site answers Yes), this will be counted as a delay. Cycle delays could occur for management of toxicity (hematologic or non-hematologic) or for administrative/logistic reasons. The reason for each cycle delay was captured in the eCRF if it was related to AEs. Reasons other than AEs were not captured." (NCT03041311)
Timeframe: Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

,
InterventionParticipants (Count of Participants)
Number of patients with any cycle delays0 cycles1 cycle2 cycles3 or more cycles
Placebo+Etoposide/Carboplatin/Atezolizumab312218103
Trilaciclib+Etoposide/Carboplatin/Atezolizumab18341422

[back to top]

Number of Participants With Any Cycle Delays and the Number of Cycles Delayed (Maintenance Period)

"After Cycle 1, patients need to meet pre-specified laboratory parameter criteria before initiating Cycle 2 and each subsequent cycle of chemotherapy. A Cycle Day Status page asks if the cycle was delayed. If the start of the current cycle was delayed (the site answers Yes), this will be counted as a delay. Cycle delays could occur for management of toxicity (hematologic or non-hematologic) or for administrative/logistic reasons. The reason for each cycle delay was captured in the eCRF if it was related to AEs. Reasons other than AEs were not captured." (NCT03041311)
Timeframe: Maintenance Period. From date of first maintenance dose, 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1160 days.

,
InterventionParticipants (Count of Participants)
Number of patients with any cycle delays0 cycles1 cycle2 cycles3 or more cycles
Placebo+Etoposide/Carboplatin/Atezolizumab26211268
Trilaciclib+Etoposide/Carboplatin/Atezolizumab21201065

[back to top]

Number of Participants With Any Dose Interruptions [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)

Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption. (NCT03041311)
Timeframe: Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

,
InterventionParticipants (Count of Participants)
Trilaciclib/placeboCarboplatinEtoposide
Placebo+Etoposide/Carboplatin/Atezolizumab013
Trilaciclib+Etoposide/Carboplatin/Atezolizumab302

[back to top]

Number of Participants With Any Dose Reductions of Carboplatin and Etoposide (Induction Period)

No dose reductions were allowed for trilaciclib or atezolizumab during the study. (NCT03041311)
Timeframe: Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

,
InterventionParticipants (Count of Participants)
EtoposideCarboplatin
Placebo+Etoposide/Carboplatin/Atezolizumab1413
Trilaciclib+Etoposide/Carboplatin/Atezolizumab31

[back to top]

Number of Participants With at Least 1 Occurrence of Severe (Grade 4) Neutropenia

The occurrence of severe (Grade 4) neutropenia (SN) was a binary variable. If a patient had at least 1 absolute neutrophil count value <0.5 × 10^9/L during the Induction Period, the patient was assigned as Yes to the occurrence of SN; otherwise, it was No. (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles up to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab1
Placebo+Etoposide/Carboplatin/Atezolizumab26

[back to top]

Progression-Free Survival

Progression-free survival (PFS) was defined as the time (number of months) from date of randomization until date of documented radiologic disease progression per RECIST v1.1 or death due to any cause, whichever came first. (NCT03041311)
Timeframe: From date of randomization, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days.

,
Interventionmonths (Number)
25%Median75%
Placebo+Etoposide/Carboplatin/Atezolizumab4.05.46.4
Trilaciclib+Etoposide/Carboplatin/Atezolizumab3.75.98.5

[back to top]

Relative Dose Intensity of Trilaciclib/Placebo, Carboplatin, Etoposide, Atezolizumab (Induction Period) and Atezolizumab (Maintenance Period)

Relative dose intensity is defined as 100% times the actual dose intensity divided by the planned dose intensity. The planned dose intensity is defined as the cumulative planned dose through the study divided by (number of cycles * 3 weeks) (NCT03041311)
Timeframe: From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 724 days.

,
Interventionpercentage of dose (Mean)
Trilaciclib/PlaceboCarboplatinEtoposideAtezolizumab (Induction)Atezolizumab (Maintenance)
Placebo+Etoposide/Carboplatin/Atezolizumab91.189.187.791.094.2
Trilaciclib+Etoposide/Carboplatin/Atezolizumab94.695.393.494.193.5

[back to top]

Number of Participants With at Least 1 Occurrence of Febrile Neutropenia

"The criterion for identifying febrile neutropenia was if the preferred term for an adverse event was FEBRILE NEUTROPENIA. Any occurrence of a febrile neutropenia event during the induction treatment period is defined as a binary variable (Yes or No); Yes if total number of febrile neutropenia events ≥ 1 is observed, No for other scenarios. Each febrile neutropenia event with a unique start date during the induction treatment period was defined as a separate event." (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab1
Placebo+Etoposide/Carboplatin/Atezolizumab3

[back to top]

Overall Survival (OS)

Overall survival was calculated as the time (months) from date of randomization to the date of death due to any cause. Patients who did not die during the study were censored at the date last known to be alive. Patients lacking data beyond the date of randomization had their survival time censored at date of randomization. Overall survival was not censored if a patient received other anti-tumor treatments after the study drugs. Overall survival was calculated using the Kaplan-Meier method. (NCT03041311)
Timeframe: From date of randomization to date of death due to any cause, assessed up to a maximum of 38.1 months.

,
InterventionMonths (Number)
25%Median75%
Placebo+Etoposide/Carboplatin/Atezolizumab6.712.822.4
Trilaciclib+Etoposide/Carboplatin/Atezolizumab7.212.020.6

[back to top]

Number of Participants With Any Missed Doses [for Each Study Drug: Trilaciclib/Placebo, Carboplatin and Etoposide] (Induction Period)

"Missed doses are identified on the dosing page of each study drug based on the question Was the dose given?. The missed dose information will be obtained for each study drug. For a study drug, if the last record of response to question Was the dose given? is No, it will not be considered as a missed dose but instead considered to be end of treatment if both criteria below are met: (1) No other study drugs are given on the same day, and (2) No study drugs are given subsequently." (NCT03041311)
Timeframe: Induction Period. From date of first dose, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

,
InterventionParticipants (Count of Participants)
Trilaciclib/PlaceboCarboplatinEtoposide
Placebo+Etoposide/Carboplatin/Atezolizumab000
Trilaciclib+Etoposide/Carboplatin/Atezolizumab313

[back to top]

All-Cause Dose Reductions

Dose reductions are not permitted for trilaciclib or atezolizumab. Dose reductions for E/P are derived from changes in the protocol-specified dose on the dosing page and correspond to the reductions for toxicity specified in the protocol. No more than 2 dose reductions of E/P in total were allowed for any patient. Simultaneous reduction in the doses of etoposide and carboplatin were counted as 1 dose reduction. (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionEvents/Cycle (Number)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab0.021
Placebo+Etoposide/Carboplatin/Atezolizumab0.085

[back to top]

Duration of Severe (Grade 4) Neutropenia in Cycle 1

Duration of severe neutropenia (DSN; days) was defined as the number of days from the date of the first absolute neutrophil count (ANC) value of <0.5 × 10⁹/L observed between start of cycle and end of cycle to the date of the first ANC value ≥0.5 × 10⁹/L that met the following criteria: (1) occurred after the ANC value of <0.5 × 10⁹/L and (2) no other ANC values <0.5 × 10⁹/L occurred between this day and end of cycle. DSN was set to 0 for patients who did not experience severe neutropenia in a cycle, including those that were randomized and not treated. Data from unscheduled visits and the actual assessment date (rather than visit date) were included in the derivation. (NCT03041311)
Timeframe: Evaluated for Cycle 1 of the Induction Period (i.e., from randomization to the end of Cycle 1, each cycle = 21 days).

Interventiondays (Mean)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab0
Placebo+Etoposide/Carboplatin/Atezolizumab4

[back to top]

Number of Participants With Any Interrupted Doses of Atezolizumab (Overall Treatment Period)

Dose interruptions were defined as interruption of infusion, regardless of whether the study drug was continued after the interruption. (NCT03041311)
Timeframe: From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab1
Placebo+Etoposide/Carboplatin/Atezolizumab0

[back to top]

Number of Participants With Any Missed Doses of Atezolizumab (Overall Treatment Period)

"Missed doses are identified on the dosing page of each study drug based on the question Was the dose given?. The missed dose information will be obtained for each study drug. For a study drug, if the last record of response to question Was the dose given? is No, it will not be considered as a missed dose but instead considered to be end of treatment if both criteria below are met: (1) No other study drugs are given on the same day, and (2) No study drugs are given subsequently." (NCT03041311)
Timeframe: From date of first dose, up to four 21-day cycles of Induction therapy, followed by 21 day cycles of Maintenance therapy until disease progression, unacceptable toxicity or discontinuation by the patient or investigator, assessed up to 1162 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab3
Placebo+Etoposide/Carboplatin/Atezolizumab3

[back to top]

Number of Participants With at Least 1 Occurrence of Erythropoiesis Stimulating Agent (ESA) Administration

"Any ESA administration in a cycle during the Induction Period was defined as a separate event. A patient with at least 1 cycle with ESA administration during an induction cycle or the Induction Period was considered to have occurrence of ESA administration. The criterion to select proper records was as follows: If the chemical subgroup from WHO-DD Version September 2017 (ie TEXT4 for CODE4) takes the value OTHER ANTIANEMIC PREPARATIONS, the medication was classified as ESAs." (NCT03041311)
Timeframe: Induction Period. From date of randomization, 21 day treatment cycles to a maximum of 4 cycles or until (if earlier) disease progression, unacceptable toxicity, or discontinuation by the patient or investigator, assessed up to a maximum of 409 days.

InterventionParticipants (Count of Participants)
Trilaciclib+Etoposide/Carboplatin/Atezolizumab3
Placebo+Etoposide/Carboplatin/Atezolizumab6

[back to top]

OS in the Global Cohort; D + T + EP Compared With D + EP

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP in the global cohort. The alternative treatment comparisons in the global cohort were performed as primary outcome measures. (NCT03043872)
Timeframe: From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Interventionmonths (Median)
Global Cohort: D + T + EP10.4
Global Cohort: D + EP12.9

[back to top]

Objective Response Rate (ORR) in the Global Cohort

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of Complete Response (CR) or Partial Response (PR). CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size [<10 mm short axis]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters). (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Interventionpercentage of patients (Number)
Global Cohort: D + T + EP74.2
Global Cohort: D + EP79.5
Global Cohort: EP70.6

[back to top]

Change From Baseline in Primary PRO Symptoms as Assessed by EORTC QLQ in the Global Cohort; D + T + EP Compared With EP

A mixed model repeated measures (MMRM) analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs P. Analysis of D + EP vs EP is presented in a separate outcome measure. (NCT03043872)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

,
Interventionscores on a scale (Mean)
EORTC QLQ-LC13 CoughEORTC QLQ-LC13 DyspneaEORTC QLQ-LC13 Chest painEORTC QLQ-C30 FatigueEORTC QLQ-C30 Appetite loss
Global Cohort: D + T + EP-15.1-6.8-7.4-6.1-8.7
Global Cohort: EP-14.6-6.6-7.0-6.3-9.5

[back to top]

Change From Baseline in Primary PRO Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the China Cohort; D + T + EP Compared With EP

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + T + EP vs EP. Analysis of D + EP vs EP is presented in a separate outcome measure. (NCT03043872)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

,
Interventionscores on a scale (Mean)
EORTC QLQ-LC13 CoughEORTC QLQ-LC13 DyspneaEORTC QLQ-LC13 Chest painEORTC QLQ-C30 FatigueEORTC QLQ-C30 Appetite loss
China Cohort: D + T + EP-12.8-3.6-5.12.83.0
China Cohort: EP-12.9-0.8-5.42.90.8

[back to top]

OS in the China Cohort; Assessed at China Cohort First Analysis; D + EP Compared With EP

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + EP vs EP in the China cohort was pre-specified at approximately 60% maturity (to ensure a similar maturity to the interim analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP at the China cohort first analysis DCO (06 January 2020), and is comparable in terms of maturity with the interim analysis of OS for D + EP vs EP in the Global cohort. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the China cohort second analysis is presented separately in the subsequent primary outcome measure. (NCT03043872)
Timeframe: From baseline until death due to any cause. Assessed until China cohort first analysis DCO (maximum of approximately 19 months).

Interventionmonths (Median)
China Cohort: D + EP14.4
China Cohort: EP10.9

[back to top]

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13) in the Global Cohort

The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (an increase in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration. (NCT03043872)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

,,
Interventionmonths (Median)
QLQ-LC13 CoughingQLQ-LC13 DyspneaQLQ-LC13 HemoptysisQLQ-LC13 Pain in Arm or ShoulderQLQ-LC13 Pain in ChestQLQ-LC13 Pain in Other Parts
Global Cohort: D + EP9.36.518.39.711.57.8
Global Cohort: D + T + EP7.76.311.47.18.57.4
Global Cohort: EP7.75.510.87.67.96.6

[back to top]

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-LC13 in the China Cohort

The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and side effects from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (an increase in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration. (NCT03043872)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

,,
Interventionmonths (Median)
QLQ-LC13 CoughingQLQ-LC13 DyspneaQLQ-LC13 HemoptysisQLQ-LC13 Pain in Arm or ShoulderQLQ-LC13 Pain in ChestQLQ-LC13 Pain in Other Parts
China Cohort: D + EP15.58.1NA15.515.59.3
China Cohort: D + T + EPNA6.9NANANANA
China Cohort: EP8.64.710.18.610.08.6

[back to top]

ORR in the China Cohort

ORR (per RECIST 1.1 using Investigator assessments) was defined as the percentage of patients with at least 1 visit response of CR or PR. CR was defined as disappearance of all TLs since baseline (any pathological lymph nodes selected as TLs must have a reduction in short axis diameter to <10 mm) or disappearance of all NTLs since baseline (all lymph nodes must be non-pathological in size [<10 mm short axis]). PR was defined as at least a 30% decrease in the sum of diameters of TLs (taking as reference the baseline sum of diameters). (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Interventionpercentage of patients (Number)
China Cohort: D + T + EP84.6
China Cohort: D + EP78.7
China Cohort: EP72.6

[back to top]

Time to Deterioration of HRQoL and PRO Symptoms, Assessed Using EORTC QLQ in the China Cohort

The EORTC QLQ-C30 v3 was included for assessing HRQoL. It assesses HRQoL/health status through 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social), 3 symptom scales (fatigue, pain, and nausea and vomiting), and a global health and QoL scale. 6 single-item symptom measures are also included: dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties. Scores from 0 to 100 were derived for each of the 15 domains, with higher scores representing greater functioning, greater HRQoL, or greater level of symptoms. Time to deterioration (calculated using the Kaplan-Meier technique) was defined as time from randomization until the date of first clinically meaningful deterioration (a decrease in score from baseline of ≥10) that is confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration. (NCT03043872)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

,,
Interventionmonths (Median)
QLQ-C30 Global Health Status / HRQoLQLQ-C30 Cognitive FunctioningQLQ-C30 Emotional FunctioningQLQ-C30 Physical FunctioningQLQ-C30 Role FunctioningQLQ-C30 Social FunctioningQLQ-C30 FatigueQLQ-C30 Nausea / VomitingQLQ-C30 PainQLQ-C30 Appetite LossQLQ-C30 ConstipationQLQ-C30 DiarrheaQLQ-C30 DyspneaQLQ-C30 Insomnia
China Cohort: D + EP15.16.815.59.36.45.85.39.36.25.812.0NA15.515.5
China Cohort: D + T + EP14.57.620.421.86.86.73.78.46.68.4NA17.311.67.3
China Cohort: EP7.86.910.07.36.26.53.98.26.56.910.910.17.37.8

[back to top]

Change From Baseline in Primary Symptoms as Assessed by EORTC QLQ in the China Cohort; D + EP Compared With EP

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + EP vs EP. Analysis of D + T + EP vs EP is presented in a separate outcome measure. (NCT03043872)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

,
Interventionscores on a scale (Mean)
EORTC QLQ-LC13 CoughEORTC QLQ-LC13 DyspneaEORTC QLQ-LC13 Chest painEORTC QLQ-C30 FatigueEORTC QLQ-C30 Appetite loss
China Cohort: D + EP-14.9-2.2-6.71.53.6
China Cohort: EP-16.7-3.0-7.70.8-2.2

[back to top]

OS in the China Cohort; D + T + EP Compared With D + EP

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This secondary outcome measure presents OS for the analysis of D + T + EP vs D + EP at the China cohort second analysis DCO (02 November 2020). The alternative treatment comparisons were performed as primary outcome measures. (NCT03043872)
Timeframe: From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Interventionmonths (Median)
China Cohort: D + T + EP16.1
China Cohort: D + EP14.4

[back to top] [back to top]

PK of Tremelimumab; Peak and Trough Serum Concentrations in the Global Cohort

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively. (NCT03043872)
Timeframe: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

Interventionμg/mL (Geometric Mean)
Week 0: peak concentrationWeek 3: trough concentrationWeek 12: trough concentration
Global Cohort: D + T + EP22.774.2457.576

[back to top]

PK of Tremelimumab; Peak and Trough Serum Concentrations in the China Cohort

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively. (NCT03043872)
Timeframe: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

Interventionμg/mL (Geometric Mean)
Week 0: peak concentrationWeek 3: trough concentrationWeek 12: trough concentration
China Cohort: D + T + EP24.344.5309.523

[back to top]

Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations in the Global Cohort

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively. (NCT03043872)
Timeframe: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the global cohort final analysis DCO (27 January 2020).

,
Interventionmicrograms/milliliter (μg/mL) (Geometric Mean)
Week 0: peak concentrationWeek 3: trough concentrationWeek 12: trough concentration
Global Cohort: D + EP502.6109.5239.3
Global Cohort: D + T + EP447.391.86199.2

[back to top]

OS in the Global Cohort; Assessed at Global Cohort Final Analysis; D + EP Compared With EP and D + T + EP Compared With EP

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. This primary outcome measure presents OS for the analysis of D + EP vs EP and D + T + EP vs EP at the time of the global cohort final analysis DCO (27 January 2020). Analysis of D + EP vs EP at the global cohort interim analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (global cohort final analysis) is presented as a secondary outcome measure. (NCT03043872)
Timeframe: From baseline until death due to any cause. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Interventionmonths (Median)
Global Cohort: D + T + EP10.4
Global Cohort: D + EP12.9
Global Cohort: EP10.5

[back to top]

Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab in the Global Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category. (NCT03043872)
Timeframe: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the global cohort final analysis DCO (27 January 2020).

,
InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (ADA positive post-baseline only)ADA positive at baseline onlyADA positive post-baseline and positive at baselinePersistently positiveTransiently positivenAb positive at any visit
Global Cohort: D + EP11000110000
Global Cohort: D + T + EP600060001

[back to top]

Number of Patients With ADA Response to Tremelimumab in the Global Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category. (NCT03043872)
Timeframe: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the global cohort final analysis DCO (27 January 2020).

InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (ADA positive post-baseline only)ADA positive at baseline onlyADA positive post-baseline and positive at baselinePersistently positiveTransiently positivenAb positive at any visit
Global Cohort: D + T + EP1150560412

[back to top]

Number of Patients With ADA Response to Tremelimumab in the China Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA (or ADA incidence) was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. The presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to tremelimumab for each indicated category. (NCT03043872)
Timeframe: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, tremelimumab). Assessed at the China cohort second analysis DCO (02 November 2020).

InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (ADA positive post-baseline only)ADA positive at baseline onlyADA positive post-baseline and positive at baselinePersistently positiveTransiently positivenAb positive at any visit
China Cohort: D + T + EP330300300

[back to top]

Number of Patients With ADA Response to Durvalumab in the China Cohort

Serum sampling for ADA assessment was conducted utilizing a tiered approach (screen, confirm, titer). ADA positive post-baseline only was also referred to as treatment-induced ADA. Treatment-emergent ADA was defined as the sum of treatment-induced ADA and treatment-boosted ADA (defined as baseline positive ADA titer that was boosted to ≥4-fold during the study period). Persistently positive was defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks between first and last positive, or an ADA positive result at the last available assessment. Transiently positive was defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples. Results are reported as number of patients with ADA responses to durvalumab for each indicated category. (NCT03043872)
Timeframe: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of IP (ie, durvalumab). Assessed at the China cohort second analysis DCO (02 November 2020).

,
InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (ADA positive post-baseline only)ADA positive at baseline onlyADA positive post-baseline and positive at baselinePersistently positiveTransiently positivenAb positive at any visit
China Cohort: D + EP000000000
China Cohort: D + T + EP000000000

[back to top]

OS in the China Cohort; Assessed at China Cohort Second Analysis; D + EP Compared With EP and D + T + EP Compared With EP

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An analysis of OS for D + T + EP vs EP in the China cohort was pre-specified at approximately 80% maturity (to ensure a similar maturity to the final analysis of the Global cohort). This primary outcome measure presents OS for analysis of D + EP vs EP and D + T + EP vs EP at the time of the China cohort second analysis DCO (02 November 2020), and is comparable in terms of maturity with the final analysis of OS for D + EP vs EP and D + T + EP vs EP in the Global cohort. Analysis of D + EP vs EP at the China cohort first analysis DCO is presented in the previous primary outcome measure. Analysis of D + T + EP vs D + EP (China cohort second analysis) is presented as a secondary outcome measure. (NCT03043872)
Timeframe: From baseline until death due to any cause. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Interventionmonths (Median)
China Cohort: D + T + EP16.1
China Cohort: D + EP14.4
China Cohort: EP10.9

[back to top]

OS18 in the China Cohort

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months. (NCT03043872)
Timeframe: At 18 months post-randomization. Assessed at the China cohort second analysis DCO (02 November 2020).

Interventionpercentage of patients (Number)
China Cohort: D + T + EP40.0
China Cohort: D + EP36.1
China Cohort: EP23.4

[back to top]

Overall Survival (OS) in the Global Cohort; Assessed at Global Cohort Interim Analysis; D + EP Compared With EP

OS was defined as the time from date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. An interim analysis of OS in the global cohort was pre-specified after approximately 318 OS events occurred each between the D + EP and EP groups (60% maturity), and between the D + T + EP and EP groups (60% maturity). At the global cohort interim analysis DCO (11 March 2019), comparison of OS in the D + EP versus (vs) EP groups had crossed the pre-specified boundary. Since these results were considered final in terms of formal statistical testing, they are presented here as a primary outcome measure. Analysis of OS for D + EP vs EP and for D + T + EP vs EP at the time of the global cohort final analysis is presented separately in the subsequent primary outcome measure. (NCT03043872)
Timeframe: From baseline until death due to any cause. Assessed until global cohort interim analysis DCO (maximum of approximately 23 months).

Interventionmonths (Median)
Global Cohort: D + EP13.0
Global Cohort: EP10.3

[back to top]

Percentage of Patients Alive and Progression Free at 12 Months (APF12) in the Global Cohort

The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PFS was calculated using the Kaplan-Meier technique. (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Interventionpercentage of patients (Number)
Global Cohort: D + T + EP16.9
Global Cohort: D + EP17.9
Global Cohort: EP5.3

[back to top]

Percentage of Patients Alive and Progression Free at 6 Months (APF6) in the Global Cohort

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique. (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Interventionpercentage of patients (Number)
Global Cohort: D + T + EP43.2
Global Cohort: D + EP45.4
Global Cohort: EP45.8

[back to top]

Percentage of Patients Alive at 18 Months (OS18) in the Global Cohort

OS18 was defined as the percentage of patients who were alive at 18 months after randomization per the Kaplan-Meier estimate of OS at 18 months. (NCT03043872)
Timeframe: At 18 months post-randomization. Assessed at the global cohort final analysis DCO (27 January 2020).

Interventionpercentage of patients (Number)
Global Cohort: D + T + EP30.7
Global Cohort: D + EP32.0
Global Cohort: EP24.8

[back to top]

PFS in the China Cohort

PFS (per RECIST 1.1 using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of TLs, taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 mm for the sum from nadir. For evaluation of NTLs, PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique. (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until China cohort second analysis DCO (maximum of approximately 29 months).

Interventionmonths (Median)
China Cohort: D + T + EP5.6
China Cohort: D + EP4.9
China Cohort: EP5.5

[back to top]

Progression-Free Survival (PFS) in the Global Cohort

PFS (per Response Evaluation Criteria in Solid Tumors, version 1.1 [RECIST 1.1] using Investigator assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Progression (ie, PD) was defined as at least a 20% increase in the sum of diameters of target lesions (TLs), taking as reference the smallest previous sum of diameters (nadir) and an absolute increase of ≥5 millimeters (mm) for the sum from nadir. For evaluation of non-target lesions (NTLs), PD was defined as unequivocal progression of existing NTLs. Median PFS was calculated using the Kaplan-Meier technique. (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until global cohort final analysis DCO (maximum of approximately 33 months).

Interventionmonths (Median)
Global Cohort: D + T + EP4.9
Global Cohort: D + EP5.1
Global Cohort: EP5.4

[back to top]

Change From Baseline in Primary Symptoms, Assessed Using EORTC QLQ-C30 and EORTC QLQ-LC13 in the Global Cohort; D + EP Compared With EP

A MMRM analysis of EORTC QLQ-C30 and EORTC QLQ-LC13 was performed for 5 primary PRO symptoms (cough, dyspnea, chest pain, fatigue and appetite loss), and considered all data from baseline to PD or 12 months, excluding visits with excessive missing data (defined as >75% missing data). An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales/symptom items, with higher scores representing greater symptom severity. An improvement in symptoms was indicated by a negative change from baseline. A positive change from baseline indicated a deterioration of symptoms. A minimum clinically meaningful change was defined as an absolute change from baseline of ≥10. This outcome measure presents change from baseline for primary PRO symptoms (reported as adjusted means) for analysis of D + EP vs EP. Analysis of D + T + EP vs EP is presented in a separate outcome measure. (NCT03043872)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever comes first). Assessed up to 12 months.

,
Interventionscores on a scale (Mean)
EORTC QLQ-LC13 CoughEORTC QLQ-LC13 DyspneaEORTC QLQ-LC13 Chest painEORTC QLQ-C30 FatigueEORTC QLQ-C30 Appetite loss
Global Cohort: D + EP-15.0-7.1-7.8-5.8-10.1
Global Cohort: EP-15.4-6.5-7.2-4.5-7.6

[back to top]

PK of Durvalumab; Peak and Trough Serum Concentrations in the China Cohort

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively. (NCT03043872)
Timeframe: Samples were collected post-dose on Day 1 (Week 0), and pre-dose on Weeks 3 and 12. Assessed at the China cohort second analysis DCO (02 November 2020).

,
Interventionμg/mL (Geometric Mean)
Week 0: peak concentrationWeek 3: trough concentrationWeek 12: trough concentration
China Cohort: D + EP432.096.24194.4
China Cohort: D + T + EP429.481.21151.0

[back to top]

APF12 in the China Cohort

The APF12 was defined as the percentage of patients who were alive and progression free at 12 months from randomization (ie, PFS rate at 12 months). PFS was calculated using the Kaplan-Meier technique. (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 12 months post-randomization.

Interventionpercentage of patients (Number)
China Cohort: D + T + EP21.0
China Cohort: D + EP12.3
China Cohort: EP6.2

[back to top]

APF6 in the China Cohort

The APF6 was defined as the percentage of patients who were alive and progression free at 6 months from randomization (ie, PFS rate at 6 months). PFS was calculated using the Kaplan-Meier technique. (NCT03043872)
Timeframe: Tumour scans performed at baseline, Week 6, Week 12 then every 8 weeks relative to the date of randomization until RECIST 1.1-defined progression. Assessed until 6 months post-randomization.

Interventionpercentage of patients (Number)
China Cohort: D + T + EP43.7
China Cohort: D + EP35.2
China Cohort: EP43.1

[back to top] [back to top]

Part A: AUClast: Area Under the Plasma and Whole Blood Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Pevonedistat

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionhour*nanogram per milliliter (hr*ng/mL) (Mean)
PlasmaWhole Blood
Part A: [14C]-Pevonedistat 25 mg/m^21446.959284.0

[back to top]

Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

(NCT03057366)
Timeframe: Part A: From first dose of study drug in Part A up to Day 31; Part B: From first dose of study drug in Part B up to Cycle 11 Day 35 (Cycle length is equal to [=] 21 days)

,,
InterventionParticipants (Count of Participants)
TEAEsSAEs
Part A: [14C]-Pevonedistat 25 mg/m^241
Part B: Pevonedistat + Docetaxel21
Part B: Pevonedistat + Paclitaxel and Carboplatin52

[back to top]

Part A: Renal Clearance (CLR) for Pevonedistat

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionliter per hour (L/hr) (Mean)
Part A: [14C]-Pevonedistat 25 mg/m^20.8343

[back to top]

Part A: Aefeces,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Feces up to the Last Sampling Interval

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionmcg eq (Mean)
Part A: [14C]-Pevonedistat 25 mg/m^225029.45

[back to top]

Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment

The best overall response was defined as the participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters as the best overall response after randomization. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PD: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). (NCT03057366)
Timeframe: Up to Cycle 11 (Cycle length =21 days)

,
InterventionParticipants (Count of Participants)
CRPRSDPD
Part B: Pevonedistat + Docetaxel0002
Part B: Pevonedistat + Paclitaxel and Carboplatin0023

[back to top]

Part A: Feurine: Cumulative Percentage of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionpercentage of dose (Mean)
Part A: [14C]-Pevonedistat 25 mg/m^22.45

[back to top] [back to top]

Part A: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionmicrogram (mcg) (Mean)
Part A: [14C]-Pevonedistat 25 mg/m^21161.47

[back to top]

Part A: Aeurine,14C: Cumulative Amount of [14C]-Pevonedistat Excreted in Urine up to the Last Sampling Interval

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionmicrogram equivalent (mcg eq) (Mean)
Part A: [14C]-Pevonedistat 25 mg/m^219661.05

[back to top]

Part A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionmcg eq (Mean)
Part A: [14C]-Pevonedistat 25 mg/m^244690.50

[back to top]

Part A: Tmax: Time to Reach the Maximum Plasma and Whole Blood Concentration (Cmax) for Pevonedistat

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionhour (Median)
PlasmaWhole Blood
Part A: [14C]-Pevonedistat 25 mg/m^20.9801.000

[back to top]

Part A: Percent Distribution of Total Radioactivity (TRA) for Pevonedistat and Its Metabolites in Plasma, Urine and Feces

(NCT03057366)
Timeframe: Up to 168 hours post-dose

Interventionpercentage distribution of TRA (Mean)
Pevonedistat in PlasmaMetabolite-1 in PlasmaMetabolite-2 in PlasmaMetabolite-3 in PlasmaMetabolite-7 in PlasmaMetabolite-10b in PlasmaMetabolite-16 in PlasmaMetabolite-22 in PlasmaPevonedistat in UrineMetabolite-1 in UrineMetabolite-2 in UrineMetabolite-3 in UrineMetabolite-7 in UrineMetabolite-10b in UrineMetabolite-16 in UrineMetabolite-22 in UrineMetabolite-23 in UrineMetabolite-24 in UrinePevonedistat in FecesMetabolite-1 in FecesMetabolite-2 in FecesMetabolite-3 in FecesMetabolite-7 in Feces
Part A: [14C]-Pevonedistat 25 mg/m^249.314.621.54.50.86.51.01.910.546.519.19.91.83.56.11.30.81.730.314.134.020.31.3

[back to top] [back to top]

Part A: Cmax: Maximum Observed Plasma and Whole Blood Concentration for Pevonedistat

(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose

Interventionnanogram per milliliter (ng/mL) (Mean)
PlasmaWhole blood
Part A: [14C]-Pevonedistat 25 mg/m^2234.36862.9

[back to top]

Change From Baseline at Week 18 in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) Global Health Status/Quality of Life Scale

EORTC QLQ-C30 is a questionnaire that rates the overall quality of life in cancer participants. The first 28 questions use a 4-point scale (1=not at all to 4=very much) for evaluating function (physical, role, social, cognitive, emotional), symptoms (diarrhea, fatigue, dyspnea, appetite loss, insomnia, nausea/vomiting, constipation, and pain) and financial difficulties. The last 2 questions use a 7-point scale (1=very poor to 7=excellent) to evaluate overall health and quality of life. Scores are transformed to a range of 0 to 100 using a standard EORTC algorithm. Change from baseline scores were calculated using a constrained longitudinal data analysis (cLDA) model. Negative change from baseline values indicated deterioration in health status or functioning and positive changes indicated improvement. Data are presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Baseline (prior to first dose of study treatment in Cycle 1 [cycle length = 21 days]) and Week 18

InterventionScore on a Scale (Least Squares Mean)
Pembrolizumab+EP8.66
Placebo+EP4.23

[back to top]

Number of Participants Discontinuing Study Treatment Due to an Adverse Event (AE)

An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who discontinued due to an AE was reported for each arm according to the treatment received and is presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Up to approximately 26 months

InterventionParticipants (Count of Participants)
Pembrolizumab+EP33
Placebo+EP14

[back to top]

Number of Participants Experiencing Any Grade 3 to 5 Adverse Events (AE) as Assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE 4.03)

The CTCAE uses Grades 1 through 5 correlating to AE severity criteria. Grade 1=mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2=moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3=severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4=life-threatening consequences; urgent intervention indicated. Grade 5=death related to AE. The number of participants who experienced any Grade 3 to 5 AE was reported for each arm according to the treatment received and is presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Up to approximately 30.5 months

InterventionParticipants (Count of Participants)
Pembrolizumab+EP175
Placebo+EP172

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also an adverse event. The number of participants who experienced an AE was reported for each arm according to the treatment received and is presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Up to approximately 30.5 months

InterventionParticipants (Count of Participants)
Pembrolizumab+EP223
Placebo+EP222

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

ORR was defined as the percentage of participants who achieve a best objective response of complete response (CR) or partial response (PR) per RECIST 1.1. CR was defined as the disappearance of all target lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions taking as a reference the baseline sum diameters. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The ORR was calculated using the Miettinen & Nurminen method stratified by type of platinum therapy (carboplatin or cisplatin), baseline ECOG performance status (0 or 1), and baseline LDH (≤ or > upper limit of normal) and presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Up to approximately 30.5 months

InterventionPercentage of Participants (Number)
Pembrolizumab+EP70.6
Placebo+EP61.8

[back to top]

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow up. The OS was calculated using the non-parametric Kaplan-Meier method for censored data and presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Up to approximately 30.5 months

InterventionMonths (Median)
Pembrolizumab+EP10.8
Placebo+EP9.7

[back to top]

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. PD, as determined by RECIST 1.1, was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. For this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The PFS was calculated using the non-parametric Kaplan-Meier method for censored data and presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Up to approximately 30.5 months

InterventionMonths (Median)
Pembrolizumab+EP4.8
Placebo+EP4.3

[back to top]

Time to True Deterioration (TTD) in the Composite Endpoint of Cough, Chest Pain, and Dyspnea Using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Lung Cancer Module 13 (QLQ-LC13)

TTD in patient-reported lung cancer symptoms of cough (QLQ-LC-13 Item 1), chest pain (QLQ-LC-13 Item 10), and dyspnea (QLQ-C30 Item 8) was a composite endpoint defined as the time to first onset of ≥10 point deterioration from baseline in an item confirmed by a second adjacent ≥10 point deterioration. The QLQ-LC13 consists of 13 measures of lung cancer symptoms and side effects from chemotherapy and radiation. It is scored on a 4-point scale (1=none, 2=a little, 3=quite a bit, 4=very much). Scores were transformed to a range of 0 to 100 using a standard algorithm. Higher scores represented increasing symptom severity. TTD was calculated using the product-limit Kaplan-Meier method for censored data and is presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Day 1 of Cycles 1-9, Day 1 of every other cycle for Cycles 10-17 and 30 days after last dose of study treatment (Up to approximately 27 months)

InterventionMonths (Median)
Pembrolizumab+EPNA
Placebo+EP8.7

[back to top]

Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)

DOR was defined as the time from first documented evidence of a Complete Response (CR) or Partial Response (PR) per RECIST 1.1 until progressive disease (PD) per RECIST 1.1 or death due to any cause, whichever occurred first. CR was defined as the disappearance of all target lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions taking as a reference the baseline sum diameters. PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. In this study, RECIST 1.1 was modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data and is presented for the first course of study treatment per protocol. (NCT03066778)
Timeframe: Up to approximately 30.5 months

InterventionMonths (Median)
Pembrolizumab+EPNA
Placebo+EPNA

[back to top]

Total Number of Participants With Gastrostomy Dependence

The prevalence of gastrostomy use up to 2 years will be described. (NCT03067610)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
Radiation Therapy31

[back to top]

Probability of Locoregional or Distant Tumor Failure

The percentage of patients with locoregional or distant failure within 2 years of treatment will be estimated using cumulative incidence statistics, with death serving as the competing risk. Cumulative incidence refers to the estimated risk/probability of tumor failure within 2 years of treatment, either locoregional recurrence or distant metastasis, accounting for the competing risk of death. (NCT03067610)
Timeframe: 2 years

Interventionpercentage of patients (Number)
Locoregional recurrenceDistant metastasis
Radiation Therapy1414

[back to top]

Quality of Life (QOL) Patient Reported Outcomes (PRO)

"Quality of life (QOL) patient-reported outcomes (PRO) for overall number of participants following treatment with elective volume and dose de-escalation, using European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30), EORTC HN35, which is specific to head and neck cancer, and composite MD Anderson Dysphagia Inventory (MDADI).~EORTC QLQ-C30 and QLQ-H&N35 are scored on a 4-point categorical scale ranging from 1 not at all to 4 very much. This scale is then linearly transformed to a 0-100 scale, where a higher score represents a higher response level. A high score for a functional scale represents higher level functioning, a high score for quality of life represents a high quality of life, and a high score for a symptom scale represents worse symptoms.~MD Anderson Dysphagia Inventory (MDADI) questionnaire: Possible score ranges from 0-100, with higher score indicating higher functioning." (NCT03067610)
Timeframe: 12 months

,,,
Interventionscore on a scale (Mean)
EORTC QLQ30 globalEORTC QLQ30 physical fcnEORTC QLQ30 role fcnEORTC QLQ30 emotional fcnEORTC QLQ30 cognitive fcnEORTC QLQ30 social fcnEORTC HN35 dry mouthEORTC HN35 sticky salivaEORTC HN35 sensesEORTC HN35 painEORTC HN35 speechComposite MDADI
Total Cohort 12 Month85.993.095.388.290.790.338.027.115.97.99.884.9
Total Cohort 3 Month76.987.482.587.789.585.159.038.025.716.513.479.6
Total Cohort 6 Month79.290.385.682.986.485.647.727.320.114.219.276.9
Total Cohort Baseline71.490.381.978.090.085.214.415.76.724.418.481.3

[back to top]

Progression-free Survival

Progression-free survival will be calculated from the initiation of treatment. Progression is confirmed by biopsy, which will be used as the date of progression. (NCT03067610)
Timeframe: 2 year

Interventionpercentage of patients (Number)
Radiation Therapy79

[back to top]

Overall Survival

Overall survival will be calculated from the initiation of treatment using the Kaplan-Meier method. (NCT03067610)
Timeframe: 2 years

Interventionpercentage of patients (Number)
Radiation Therapy89

[back to top]

Number of Patients With Solitary Elective Volume Recurrence

The crude risk of 2-year solitary elective volume recurrence will be calculated among all patients who are followed for at least 2 years. Patients who die before 2 years without an SEVR will be included in the denominator. (NCT03067610)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
Radiation Therapy0

[back to top] [back to top]

Phases 1 and 2: Number of Participants With Dose Limiting Toxicities (DLTs)

A DLT was defined as the occurrence of any of the protocol-specified toxicities occurring up to and including Day 28 for the cohorts where mFOLFOX6 and nab-paclitaxel/gemcitabine are administered and Day 21 for all other chemotherapy regimens in Phase 1, except those with a clear alternative explanation (eg, disease progression) or transient (≤ 72 hours) abnormal laboratory values without associated clinically significant signs or symptoms based on investigator determination. (NCT03085914)
Timeframe: 28 days

InterventionParticipants (Count of Participants)
Group A: Epa + Pembrolizumab + mFOLFOX62
Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine0
Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin0
Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent0
Group E: Epa + Pembrolizumab + Cyclophosphamide0
Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent3
Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent0

[back to top]

Phases 1 and 2: Objective Response Rate (ORR)

ORR was defined as the percentage of participants having a complete response (CR) or partial response (PR) as determined by investigator assessment of radiographic disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. (NCT03085914)
Timeframe: Up to Week 18

,,,,,,
InterventionParticipants (Count of Participants)
Complete ResponsePartial Response
Group A: Epa + Pembrolizumab + mFOLFOX605
Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine12
Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin03
Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent02
Group E: Epa + Pembrolizumab + Cyclophosphamide03
Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent01
Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent05

[back to top]

Phases 1 & 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs

A TEAE is any AE either reported for the first time or worsening of a pre-existing event after first dose of epacadostat, pembrolizumab, or chemotherapy. Serious adverse event is defined as an event that meets 1 of the following criteria: is fatal or life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability, incapacity, or a substantial disruption of a person's ability to conduct normal life functions, constitutes a congenital anomaly or birth defect,is a medically important event that may jeopardize the participant or may require medical or surgical intervention to prevent 1 of the outcomes listed above. (NCT03085914)
Timeframe: Up to 21 months

,,,,,,
InterventionParticipants (Count of Participants)
TEAESerious TEAE
Group A: Epa + Pembrolizumab + mFOLFOX695
Group B: Epa + Pembrolizumab + Nab-Paclitaxel and Gemcitabine95
Group C: Epa + Pembrolizumab + Paclitaxel and Carboplatin113
Group D: Epa + Pembrolizumab + Pemetrexed and Platinum Agent96
Group E: Epa + Pembrolizumab + Cyclophosphamide134
Group F: Epa + Pembrolizumab + Gemcitabine and Platinum Agent86
Group G: Epa + Pembrolizumab + 5-FU and Platinum Agent115

[back to top]

Duration of Response (DOR [as Assessed by the IRRC])

The lower and upper limits of 95% CI for the median are censored value in the both groups. (NCT03117049)
Timeframe: Approximately 32 months

Interventionmonths (Median)
ONO-4538 Group11.0
Placebo Group7.0

[back to top]

Overall Survival (OS)

(NCT03117049)
Timeframe: Approximately 32 months

Interventionmonths (Median)
ONO-4538 Group25.4
Placebo Group24.7

[back to top]

Disease Control Rate (DCR [as Assessed by the IRRC])

DCR represents the proportion of subjects whose best overall response was assessed as CR, PR, or stable disease (SD). Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria. (NCT03117049)
Timeframe: Approximately 32 months

Interventionpercentage of participants (Number)
ONO-4538 Group87.3
Placebo Group89.8

[back to top]

Best Overall Response (BOR [as Assessed by the IRRC])

(NCT03117049)
Timeframe: Approximately 32 months

,
InterventionParticipants (Count of Participants)
Complete responsePartial responseStable diseaseProgressive diseaseNot evaluable
ONO-4538 Group1415571530
Placebo Group81311081117

[back to top]

Progression Free Survival (PFS) as Assessed by the Independent Radiology Review Committee (IRRC)

"PFS (as assessed by the IRRC) will be calculated using the following formula : PFS (days) = date when overall response is assessed as progressive disease (PD) or date of death (for any reason), whichever comes first - date of randomization + 1. Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria." (NCT03117049)
Timeframe: Approximately 32 months

Interventionmonths (Median)
ONO-4538 Group12.1
Placebo Group8.1

[back to top]

Objective Response Rate (ORR [as Assessed by the IRRC])

ORR represents the proportion of subjects whose best overall response was assessed as complete response (CR) or partial response (PR). Please refer to the protocol, in this study, tumor response will be evaluated by CT, etc. according to the RECIST 1.1 criteria. (NCT03117049)
Timeframe: Approximately 32 months

Interventionpercentage of participants (Number)
ONO-4538 Group61.5
Placebo Group50.5

[back to top]

Disease Control Rate (DCR) in Patients Treated With CNP

the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention. Responses are defined as Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study (NCT03121352)
Timeframe: Up to 24 months

InterventionParticipants (Count of Participants)
Carboplatin + Nab-paclitaxel + Pembrolizumab21

[back to top]

Progression-free Survival (PFS) in Patients Treated With CNP

Average time (in months) patient's tumors did not progress according to the RECIST criteria (V1.1). Progressive disease is defined as Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (NCT03121352)
Timeframe: Up to 24 months

Interventionmonths (Mean)
Carboplatin + Nab-paclitaxel + Pembrolizumab5.8

[back to top]

Duration of Response in Patients Treated With CNP

Average time patients have a response, as defined by the RECIST criteria (V1.1). Response includes: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT03121352)
Timeframe: Up to 24 months

InterventionMonths (Median)
CompletePartial
Carboplatin + Nab-paclitaxel + PembrolizumabNA6.3

[back to top]

Overall Response Rate (ORR) in Patients Treated With CNP

The number of people with tumor responses according to RECIST (V1.1). These responses include Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study (NCT03121352)
Timeframe: Up to 24 months

InterventionParticipants (Count of Participants)
Complete Response (CR)Partial Response (PR)Progressive Disease (PD)Stable Disease (SD)
Carboplatin + Nab-paclitaxel + Pembrolizumab21168

[back to top]

Overall Survival With an Accelerated and Adaptive RT Approach.

The overall survival (OS) for the treated participants will be characterized by Kaplan-Meier estimator. The medial OS will be estimated with a 95% confidence interval. (NCT03128008)
Timeframe: 2 years

Interventionmonths (Median)
Carboplatin/Paclitaxel With Radiation TherapyNA

[back to top]

Progression-free Survival (PFS) With an Accelerated and Adaptive RT Approach.

Median progression-free survival for participants will be characterized by Kaplan-Meier estimator. The median PFS will be estimated as well as their 95% confidence intervals. (NCT03128008)
Timeframe: 2 years

Interventionmonths (Median)
Carboplatin/Paclitaxel With Radiation Therapy13.39

[back to top]

The Number of Participants Eligible for an RT Boost After Completing a Standard Dose of RT (60 Gy), Delivered in an Accelerated Fashion (6 Fractions/Week) With Concurrent Chemotherapy

In the same participant cohort, the proportion of the participants who are eligible for an RT boost after completing a standard dose of RT (60 Gy), delivered in an accelerated fashion (6 fractions/week) with concurrent chemotherapy, will be estimated as well as its confidence interval. (NCT03128008)
Timeframe: 4 weeks

InterventionParticipants (Count of Participants)
Carboplatin/Paclitaxel With Radiation Therapy3

[back to top]

Number of Participants With Local Control With an Accelerated and Adaptive RT Approach

The local control rate for the same cohort of participants will be measured by standard of care imaging per NCCN guidelines at routine follow up clinic visits. (NCT03128008)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
Carboplatin/Paclitaxel With Radiation Therapy1

[back to top]

Number of Participants Experiencing Dose-Limiting Toxicities in Dose Optimization Cohort 1a

"DLTs were assesses in the Dose Optimization Cohort 1 a, which had doses of NKTR-214 as 0.008 mg/kg, 0.010 mg/kg, and 0.012 m/kg, I combination with pembrolizumab at 200 mg.~A single DLT (hypotension) was reported in 1 patient in dose optimization Cohort 1a." (NCT03138889)
Timeframe: DLTs were assessed at 21 days from Cycle 1

,,
InterventionParticipants (Count of Participants)
At least 1 DLTVascular Disorders: Hypotension
Dose Optimization Cohort 1a: NKTR-214 (0.008 mg/kg) + Pembro (200 mg)00
Dose Optimization Cohort 1a: NKTR-214 (0.010 mg/kg) + Pembro (200 mg)11
Dose Optimization Cohort 1a: NKTR-214 (0.012 mg/kg) + Pembro (200 mg)00

[back to top]

Number of Participants With Treatment-Emergent Adverse Events [Safety and Tolerability] for Dose Optimization Cohort 1a.

Safety and Tolerability of NKTR-214 (starting at dose of 0.008 mg/kg) in combination with pembrolizumab (Keytruda®) as evaluated by incidence of drug-emergent Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to drug discontinuation, and fatal AEs. (NCT03138889)
Timeframe: AEs reported starting immediately after first dose of study drug(s) until 100 days after the last dose of all study drugs, up to approximately 28 months.

,,,
InterventionParticipants (Count of Participants)
Subjects Reporting at Least One TEAESubjects Reporting at Least One Serious TEAESubjects Reporting at Least One TEAE Leading to DeathSubjects Reporting at Least One TEAE Leading to Drug Discontinuation
NKTR-214 (0.008 mg/kg) + Pembro (200 mg)4202
NKTR-214 (0.010 mg/kg) + Pembro (200 mg)7403
NKTR-214 (0.012 mg/kg) + Pembro (200 mg)7201
Total18806

[back to top]

Objective Response Rate (ORR) Per Investigator's Assessment by RECIST 1.1 of NKTR-214 at a Dose of 0.006 mg/kg With Pembrolizumab and Platinum-based Chemotherapy for Dose Expansion Cohorts 4+5.

"ORR per Investigator's Assessment* by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 4 +5. The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response.~Objective response is the sum of confirmed complete response and confirmed partial response.~*Efficacy endpoint for Cohort 4 +5 is per Investigator's Assessment due to the early termination of the study and incompleteness of BICR data for these cohorts." (NCT03138889)
Timeframe: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discont. treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.

InterventionParticipants (Count of Participants)
Dose Expansion Cohorts 4/52

[back to top]

Objective Response Rate (ORR) Per Blinded Independent Central Review (BICR) by RECIST 1.1 of NKTR-214 Plus Pembrolizumab for Dose Expansion Cohorts 2 and 3.

"ORR per BICR by RECIST 1.1 for the Response Evaluable Population dose expansion Cohorts 2 and 3.~ORR is defined as the proportion of enrolled participants who achieved a Best Overall Response (BOR) of CR or PR. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to < 10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR is calculated as the sum of CR and PR.~The Response Evaluable Population was subjects who received at least 1 dose (or partial dose) of study drug, had measurable disease (per RECIST 1.1) at baseline, and had at least 1 post-baseline assessment of tumor response." (NCT03138889)
Timeframe: Until disease progression, death, unacceptable toxicity, symptomatic deterioration, Investigator's decision to discontinue treatment, patient withdrew consent or lost to follow-up, or study terminated by Sponsor; or until maximum of 2 years.

InterventionParticipants (Count of Participants)
Dose Expansion Cohort 2: NKTR-214 (0.006 mg/kg) + Pembro (200 mg)13
Dose Expansion Cohort 3: NKTR-214 (0.010 mg/kg) + Pembro (200 mg)2

[back to top] [back to top]

PK of Tremelimumab; Peak and Trough Serum Concentrations

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of tremelimumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively. (NCT03164616)
Timeframe: Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.

Interventionμg/mL (Geometric Mean)
Week 0Week 3Week 12Follow-up (3 months)
T + D + SoC23.174.167.820.86

[back to top]

Time From Randomization to Second Progression (PFS2)

PFS2 was defined as the time from the date of randomization to the earliest of the progression event (subsequent to that used for the primary variable PFS) or death. The date of second progression was recorded by the Investigator and defined according to local standard clinical practice and could involve any of: objective radiological imaging, symptomatic progression or death. (NCT03164616)
Timeframe: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Interventionmonths (Median)
T + D + SoC10.4
D + SoC10.2
SoC Alone9.4

[back to top]

Progression-Free Survival (PFS); D + SoC Compared With SoC Alone

PFS (per RECIST version 1.1 [RECIST 1.1] using Blinded Independent Central Review [BICR] assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique. The final analysis of PFS in the global cohort was pre-specified after approximately 497 BICR PFS events occurred across the D + SoC and SoC alone treatment arms (75% maturity). (NCT03164616)
Timeframe: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Interventionmonths (Median)
D + SoC5.5
SoC Alone4.8

[back to top]

PFS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC

PFS (per RECIST 1.1 using BICR assessments) was defined as time from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression. Median PFS was calculated using the Kaplan-Meier technique. (NCT03164616)
Timeframe: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months.

Interventionmonths (Median)
T + D + SoC6.2
D + SoC5.5
SoC Alone4.8

[back to top]

Overall Survival (OS); D + SoC Compared With SoC Alone

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. The final analysis of OS in the global cohort was pre-specified after approximately 532 OS events occurred across the D + SoC and SoC alone treatment arms (80% maturity). (NCT03164616)
Timeframe: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Interventionmonths (Median)
D + SoC13.3
SoC Alone11.7

[back to top]

OS; T + D + SoC Compared With SoC Alone and T + D + SoC Compared With D + SoC

OS was defined as the time from the date of randomization until death due to any cause. Any patient not known to have died at the time of analysis was censored based on the last recorded date on which the patient was known to be alive. Median OS was calculated using the Kaplan-Meier technique. (NCT03164616)
Timeframe: From baseline until death due to any cause. Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

Interventionmonths (Median)
T + D + SoC14.0
D + SoC13.3
SoC Alone11.7

[back to top]

Objective Response Rate (ORR)

ORR (per RECIST 1.1 using BICR assessments) was defined as the percentage of patients with at least one visit response of complete response (CR) or partial response (PR). Results are presented for the pre-specified ORR analysis using unconfirmed responses based on BICR. (NCT03164616)
Timeframe: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Interventionpercentage of patients (Number)
T + D + SoC46.3
D + SoC48.5
SoC Alone33.4

[back to top]

Duration of Response (DoR)

DoR (per RECIST 1.1 using BICR assessments) was defined as the time from the date of first documented response until date of documented progression or death in the absence of disease progression. The end of response coincided with the date of progression or death from any cause used for the RECIST 1.1 PFS endpoint. The time of the initial response was defined as the latest of the dates contributing towards the first visit of PR or CR. Results are presented for the pre-specified DoR analysis using unconfirmed responses based on BICR. (NCT03164616)
Timeframe: Tumor scans performed at baseline, Week 6, Week 12 and then every 8 weeks relative to date of randomization until radiological progression. Assessed until global cohort DCO of 24 July 2019 (maximum of approximately 25 months).

Interventionmonths (Median)
T + D + SoC7.4
D + SoC6.0
SoC Alone4.2

[back to top]

Pharmacokinetics (PK) of Durvalumab; Peak and Trough Serum Concentrations

To evaluate PK, blood samples were collected at pre-specified timepoints and peak and trough serum concentrations of durvalumab were determined. Peak concentration on Week 0 is the post-infusion concentration of Week 0 (collected within 10 minutes of the end of infusion). Trough concentrations on Weeks 3 and 12 are the pre-infusion concentrations of Weeks 3 and 12, respectively. (NCT03164616)
Timeframe: Samples were collected post-dose on Day 1 (Week 0), pre-dose on Weeks 3 and 12 and at follow-up (3 months after the last valid dose). Assessed at the global cohort DCO of 12 March 2021.

,
Interventionmicrograms/milliliter (μg/mL) (Geometric Mean)
Week 0Week 3Week 12Follow-up (3 months)
D + SoC505.0191.53212.1116.06
T + D + SoC418.8082.08195.6213.42

[back to top]

Number of Patients With Anti-Drug Antibody (ADA) Response to Durvalumab

Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against durvalumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of neutralizing antibody (nAb) was tested for all ADA positive samples. (NCT03164616)
Timeframe: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, durvalumab).

,
InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (ADA positive post-baseline only)ADA positive at baseline onlyADA positive post-baseline and positive at baselinePersistently positiveTransiently positivenAb positive at any visit
D + SoC33191181327133
T + D + SoC4229227878263

[back to top]

Number of Patients With ADA Response to Tremelimumab

Blood samples were collected at pre-specified timepoints and number of patients who developed detectable ADAs against tremelimumab was determined. ADA prevalence is defined as percentage of patients with positive ADA result at any time, baseline or post-baseline. Treatment-emergent ADA is defined as either treatment-induced ADA or treatment-boosted ADA. ADA incidence is percentage of patients who were treatment-emergent ADA-positive. Treatment-boosted ADA is defined as baseline positive ADA titer that was boosted by ≥4-fold during the study period. Persistently positive is defined as having ≥2 post-baseline ADA positive measurements with ≥16 weeks (112 days) between the first and last positive, or an ADA positive result at the last available assessment. Transiently positive is defined as having ≥1 post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive. Presence of nAb was tested for all ADA positive samples. (NCT03164616)
Timeframe: Samples were collected on Day 1 (Week 0), Week 12 and at 3 months after the last dose of study treatment (ie, tremelimumab).

InterventionParticipants (Count of Participants)
ADA positive at any visit (ADA prevalence)Treatment-emergent ADA positive (ADA incidence)Treatment-boosted ADATreatment-induced ADA (ADA positive post-baseline only)ADA positive at baseline onlyADA positive post-baseline and positive at baselinePersistently positiveTransiently positivenAb positive at any visit
T + D + SoC443833545221831

[back to top]

Time to Deterioration of PRO Symptoms, Assessed Using EORTC QLQ-Lung Cancer Module 13 (QLQ-LC13)

The EORTC QLQ-LC13 is a disease-specific 13-item self-administered questionnaire for lung cancer, to be used in conjunction with the EORTC QLQ-C30. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, hemoptysis, dyspnea, and pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores from 0 to 100 were derived for each symptom item, with higher scores representing greater level of symptoms. Time to deterioration was defined as time from randomization until the date of first clinically meaningful deterioration that was confirmed at a subsequent visit or death (by any cause) in the absence of a clinically meaningful deterioration. (NCT03164616)
Timeframe: At baseline, Weeks 3, 6, 9, 12, 16 and 20, then Q4W until PD, on Day 28 and 2 months post-PD, then every 8 weeks until second progression/death (whichever came first). Assessed until global cohort DCO of 12 March 2021 (maximum of approximately 45 months).

,,
Interventionmonths (Median)
QLQ-LC13 CoughQLQ-LC13 HemoptysisQLQ-LC13 DyspneaQLQ-LC13 Pain in ChestQLQ-LC13 Pain in Arm or ShoulderQLQ-LC13 Pain in Other Parts
D + SoC11.014.05.09.58.98.9
SoC Alone8.811.43.68.68.85.8
T + D + SoC9.717.85.410.08.99.7

[back to top]

Pathologic Complete Response Rate (pCRR) After Induction Chemotherapy With Carboplatin, Nab-paclitaxel, and Durvalumab in Previously Untreated Stage III and IV SCCHN Amenable to Surgical Resection

The pCRR was assessed via surgical pathology report. Pathologic complete response will require no viable cancer cells on the surgical pathology report after neoadjuvant treatment with carboplatin, nab-paclitaxel, and durvalumab. This study protocol requires the same neoadjuvant therapy and surgery for all subjects. The primary outcome measure is the complete pathologic response defined by the surgical pathology report and is unrelated to adjuvant therapy. (NCT03174275)
Timeframe: After surgery (approximately 8-12 weeks after start of study treatment)

InterventionParticipants (Count of Participants)
Pathologic complete response was achievedPathologic complete response was not achieved
Pathologic Complete Response1025

[back to top]

Number of Patients Completing the Protocol

Defined as completion of vaginal cuff brachytherapy followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy (NCT03189446)
Timeframe: 4 months

InterventionParticipants (Count of Participants)
Vaginal Cuff Brachytherapy + Chemotherapy27

[back to top] [back to top]

Median Overall Survival Time

Overall survival is defined as the time from study enrollment to death from any cause. Estimated using a Kaplan-Meier analysis. (NCT03194373)
Timeframe: Up to 2 Years

Interventionmonths (Median)
Palbociclib and Carboplatin4.6

[back to top]

Median Progression Free Survival Time

Progression-free survival (PFS) is defined as the duration of time from start of treatment to time of progression. Progressive disease is defined as at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started, or the appearance of one or more new lesions. Estimated using a Kaplan-Meier analysis. (NCT03194373)
Timeframe: Up to 2 Years

Interventionmonths (Median)
Palbociclib and Carboplatin2.9

[back to top]

Percent Disease Control Rate (DCR)

The primary clinical objective of this trial is to estimate disease control rate (DCR) at 12 weeks in patients with metastatic head and neck squamous cell cancer treated with carboplatin and palbociclib. DCR will be defined as either CR (Complete Response: Disappearance of all target lesions, determined by two separate observations conducted not less than 4 weeks apart. There can be no appearance of new lesions.), PR (Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. There can be no appearance of new lesions.) or SD (Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.) at 12 weeks. (NCT03194373)
Timeframe: 12 weeks

Interventionpercentage of participants (Number)
Palbociclib and Carboplatin33

[back to top] [back to top]

Clinical Benefit Rate (CBR)

Patient response to treatment was evaluated by RECIST 1.1. The CBR (CR + PR+stable disease ≥ 6 months) and corresponding 95% confidence intervals (exact) were estimated among evaluable patients. (NCT03206203)
Timeframe: Up to 3 years

Interventionpercentage of participants (Number)
Arm 1 (Atezolizumab, Carboplatin)38.9
Arm 2 (Carboplatin)20.0

[back to top]

Duration of Response (DOR)

DOR was defined as the time from CR or PR to progression using RECIST V1.1. The median DOR and corresponding 95% confidence intervals was estimated uisng Kaplan-Meier method. (NCT03206203)
Timeframe: Up to 3 years

Interventionmonths (Median)
Arm 1 (Atezolizumab, Carboplatin)11.6
Arm 2 (Carboplatin)14.8

[back to top]

Overall Response Rate (ORR)

Patient response to treatment was evaluated by RECIST V1.1. The ORR (CR + PR) and corresponding 95% confidence intervals (exact) were estimated among evaluable patients. (NCT03206203)
Timeframe: Up to 3 years

Interventionpercentage of participants (Number)
Arm 1 (Atezolizumab, Carboplatin)31.5
Arm 2 (Carboplatin)8.9

[back to top]

Progression Free Survival (PFS)

The PFS is defined as the time from the first day of treatment to the first observation of disease progression (RECIST V1.1) or death of any cause. Those without events were censored at the last follow up. The median PFS time will be estimated using the Kaplan-Meier method with 95% confidence intervals. (NCT03206203)
Timeframe: Up to 3 years.

Interventionmonths (Median)
Arm 1 (Atezolizumab, Carboplatin)4.1
Arm 2 (Carboplatin)2.2

[back to top]

Overall Survival (OS)

OS is defined as the time from first day of treatment to death. Those alive were censored at the last follow up. The median and OS time and corresponding 95% confidence intervals were estimated using Kaplan-meier method. (NCT03206203)
Timeframe: Up to 3 years.

Interventionmonths (Median)
Arm 1 (Atezolizumab, Carboplatin)12.6
Arm 2 (Carboplatin)7.0

[back to top]

Overall Survival (OS)

OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date. (NCT03215706)
Timeframe: From date of randomization to date of death (assessed up to October 2019, approximately 23 months)

InterventionMonths (Median)
Treatment A14.13
Treatment B10.74

[back to top]

Objective Response Rate (ORR) by BICR by PD-LI Tumor Cell Expression

PD-L1 expression was defined as the percent of tumor cells with membrane staining in a minimum of 100 evaluable tumor cells per validated Dako PD-L1 IHC 28-8 pharmDx test. PD-L1 expression was classified as PD-L1 ≥1% (≥1% tumor cells with membrane staining in a minimum of a hundred evaluable tumor cells), PD-L1 < 1% and PD-L1 not quantifiable (without quantifiable PD-L1 expression), PD-L1 expression ≥ 50%, PD-L1 expression 1 to 49% (NCT03215706)
Timeframe: From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months)

,
InterventionPercentage of Participants (Number)
BASELINE PD-L1 EXPRESSION ≥1%BASELINE PD-L1 EXPRESSION < 1%Non-Quantifiable PD-L1 ExpressionBASELINE PD-L1 EXPRESSION 1 - 49%BASELINE PD-L1 EXPRESSION >= 50%
Treatment A41.931.133.337.848.7
Treatment B27.620.928.024.530.9

[back to top]

OS by PD-L1 Tumor Cell Expression

OS was defined as the time from randomization to the date of death from any cause. OS was censored on the last date a subject was known to be alive. Survival follow-up was to be conducted every 3 months after participants's off-treatment date. (NCT03215706)
Timeframe: From date of randomization to date of death (assessed up to October 2019, approximately 23 months)

,
InterventionMonths (Median)
< 1% PD-L1 Expression>= 1% PD-L1 Expressionwith 1-49% PD-L1 Expressionwith >= 50% PD-L1 ExpressionNon-Quantifiable PD-L1 Expression
Treatment A14.0314.2314.4614.1310.84
Treatment B9.9510.5810.2511.8617.05

[back to top]

PFS by BICR by PD-L1 Tumor Cell Expression

PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first. (NCT03215706)
Timeframe: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months)

,
InterventionMonths (Median)
< 1% PD-L1 Expression>= 1% PD-L1 Expressionwith 1-49% PD-L1 Expressionwith >= 50% PD-L1 ExpressionNon-Quantifiable PD-L1 Expression
Treatment A5.827.036.748.286.14
Treatment B4.864.705.294.275.78

[back to top]

Objective Response Rate (ORR) by BICR

ORR was defined as the number of randomized participants with a best overall response (BOR) of confirmed CR or PR based on BICR assessments (using RECIST v1.1 criteria), divided by the number of all randomized participants. BOR was recorded between the date of randomization and the date of objectively documented progression per RECIST 1.1 or the date of initiation of palliative local therapy or the date of initiation of subsequent anti-cancer therapy, whichever occurred first. For participants without documented progression or palliative local therapy or subsequent anti-cancer therapy, all available response designations contributed to the BOR determination. For participants who continued treatment beyond progression, the BOR was determined based on response designations recorded up to the time of the initial RECIST 1.1 defined progression. (NCT03215706)
Timeframe: From date of randomization until date of documented tumor progression or subsequent anti-cancer therapy, whichever occurs first (assessed up to October 2019, approximately 23 months)

InterventionPercentage of Participants (Number)
Treatment A37.7
Treatment B25.1

[back to top]

Duration of Response (DoR)

DoR was defined as the time between the date of first confirmed documented response (CR or PR) to the date of the first documented BICR-assessed tumor progression (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who started subsequent therapy (including palliative local therapy) without a prior reported progression were censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy (including palliative local therapy). Participants who died without a reported prior progression were considered to have progressed on the date of their death. For subjects who neither progressed nor died, DoR was censored on the date of their last evaluable tumor assessment. DoR was evaluated for responders (confirmed CR or PR) only. (NCT03215706)
Timeframe: From date of first confirmed response to date of tumor progression (assessed up to October 2019, approximately 23 months)

InterventionMonths (Median)
Treatment A10.02
Treatment B5.09

[back to top]

Progression Free Survival (PFS) by BICR

PFS (primary definition) was defined as the time from the randomization date to the date of the first documented tumor progression based on BICR assessment (per RECIST 1.1), or death from any cause, whichever occurred first. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Participants who had not progressed or died were censored on the date of their last evaluable tumor assessment. Participants who did not have any on-study tumor assessments and did not die were censored on the randomization date. Participants who started any palliative local therapy or subsequent anticancer therapy without a prior reported progression were censored at the last evaluable tumor assessment prior to initiation of the palliative local therapy or subsequent anti-cancer therapy, whichever procedure occurred first. (NCT03215706)
Timeframe: From date of randomization until date of documented tumor progression or death due to any cause, whichever occurs first (assessed up to October 2019, approximately 23 months)

InterventionMonths (Median)
Treatment A6.83
Treatment B4.96

[back to top]

Time to Response (TTR)

TTR was defined as the time from randomization to the date of the first confirmed documented response (CR or PR), as assessed by the BICR. TTR was evaluated for responders (confirmed CR or PR) only. (NCT03215706)
Timeframe: From date of randomization to date of first confirmed documented response (assessed up to October 2019, approximately 23 months)

InterventionMonths (Median)
Treatment A2.51
Treatment B1.56

[back to top]

Progression Free Survival (PFS)

"Time from initiation of the study drugs to progression or death, whichever occurs first. Disease progression was assessed via RECIST 1.1~Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study(this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progression).~Confidence Intervals (CIs) were calculated using the Kaplan Meier (KM) method" (NCT03256136)
Timeframe: From the start of treatment until disease progression or death due to any cause, up to approximately 2 years

Interventionmonths (Median)
Nivolumab Plus Ipilimumab EGFR1.3
Nivolumab Plus Ipilimumab ALK0.7
Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive4.65
Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive2.8

[back to top]

Overall Survival (OS)

Time from initiation of the study drugs to date of death due to any cause. CIs are the KM estimate CIs. (NCT03256136)
Timeframe: From the start of treatment until death due to any cause, up to approximately 2 years

Interventionmonths (Median)
Nivolumab Plus Ipilimumab EGFR22.3
Nivolumab Plus Ipilimumab ALK7.6
Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive7.75
Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive15.9

[back to top]

Objective Response Rate (ORR), Presented in Numbers of Participants

"Complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1)~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.~Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters." (NCT03256136)
Timeframe: Up to approximately 2 years

InterventionParticipants (Count of Participants)
Nivolumab Plus Ipilimumab EGFR0
Nivolumab Plus Ipilimumab ALK0
Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive1
Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive1

[back to top]

Disease Control Rate (DCR), Presented in Numbers of Participants

"The number of patients that achieved either complete response (CR), partial response (PR), or stable disease (SD) per RECIST version 1.1~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.~Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study." (NCT03256136)
Timeframe: Up to approximately 2 years

InterventionParticipants (Count of Participants)
Nivolumab Plus Ipilimumab EGFR0
Nivolumab Plus Ipilimumab ALK0
Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive3
Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive1

[back to top]

Duration Of Response

"Time from the first documentation of objective tumor response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.~Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.~Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study(this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note:the appearance of one or more new lesions is also considered progression)." (NCT03256136)
Timeframe: From the first documented response until disease progression or death, up to approximately 2 years

Interventionmonths (Median)
Nivolumab Plus Ipilimumab EGFRNA
Nivolumab Plus Ipilimumab ALKNA
Nivolumab + Carboplatin + Pemetrexed With EGFR Chemo Naive0.9
Nivolumab + Carboplatin + Pemetrexed ALK Chemo Naive1.4

[back to top]

Phase 2: Number of Subjects Who Achieved cCR (Clinical Complete Response) or pCR (Pathological Complete Response)

Clinical and pathological response after neoadjuvant therapy cCR by endoscopic + PET/CT evaluation; pCR for patients undergoing surgery Clinical Complete Response (cCR), no malignancy is found on clinical examination, imaging, endoscopy, and biopsy; Pathological Complete Response (pCR), no invasive and no in situ residual tumors in tissue (NCT03278626)
Timeframe: 5-8 Weeks post radiation treatment (7-8 months after treatment start)

InterventionParticipants (Count of Participants)
Nivolimumab+Carboplatin/Paclitaxel+Radiation1

[back to top]

Phase 1: Number of Unacceptable Toxicity (UT) Events

"UT is defined as:~Recurrent grade 3 or 4 hematologic toxicity (despite 1 prior dose reduction in chemotherapy)~any toxicity that results in a > 2-week delay in chemoradiation" (NCT03278626)
Timeframe: 92 days (up to 28 days after Day 64)

InterventionUnacceptable Toxicity Events (Number)
Nivolimumab+Carboplatin/Paclitaxel+Radiation0

[back to top]

Pathologic Complete Response Rate

The number of participants that achieve a pathologic complete response at surgery following FOLFIRINOX and chemoradiation. All patients will undergo a full pathological review of their surgical specimen according to the American Joint Committee on Cancer (AJCC) Staging Classification, 6th edition. Initial gross evaluation and identification of resection margins will be performed jointly by the surgeon and the pathologist. Pathological complete response will be defined as the absence of any viable tumor cells within the pathologic specimen. (NCT03279237)
Timeframe: 29 Weeks

InterventionParticipants (Count of Participants)
FOLFIRINOX + Pre-operative Radiation7

[back to top]

The Completion Rate of Chemotherapy in Combination With Chemoradiation

The number of participants that complete the assigned study intervention. (NCT03279237)
Timeframe: 21 weeks

InterventionParticipants (Count of Participants)
FOLFIRINOX + Pre-operative Radiation23

[back to top]

Clinical Response Rate

"The number of participants that achieved a clinical response following treatment. Clinical response is defined as achieving a best overall response of a complete response (CR) or a partial response (PR).~Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.~Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters." (NCT03279237)
Timeframe: After 4 and 8 cycles of FOLFIRINOX (8 and 16 weeks); and 3-4 weeks after chemo radiation (24-25 weeks)

InterventionParticipants (Count of Participants)
FOLFIRINOX + Pre-operative Radiation20

[back to top] [back to top]

Incidence of Treatment-emergent Adverse Events (TEAEs)

Comparison of Safety profile. Safety was monitored by incidence of adverse events (AEs). AEs were coded as per MedDRA (version 20.1) and severity was graded according to NCI-CTCAE (version 4.03); (NCT03296163)
Timeframe: Week 1 to week 52

,
Interventionparticipants (Number)
with ≥1 TEAEwith ≥1 Grade 3 or 4 TEAEwith ≥1 treatment-related TEAEwith ≥1 Grade 3 or 4 treatment-related TEAEwith at least one Serious TEAEwith ≥1 TEAE leading to discontinuationwith ≥1 treatment-related TEAE leading to discontinuation
EU-approved Avastin®28812527091546333
MB02 (Bevacizumab Biosimilar Drug)28813126498587242

[back to top]

Immunogenicity Assessments (Anti-drug Antibodies [ADA] and Neutralizing Antibodies [NAb])

Incidence of anti-drug antibodies (ADA) and neutralizing ADAs (NAb). Analyses of ADA incidence rate, antibody titer, and neutralizing antibodies (NAb) (following the recommended 3-tier approach) were performed. (NCT03296163)
Timeframe: At Weeks 1, 4, 10, 19, 34 and 52 from randomization and, at the End of Treatment Visit if, an ADA sample has not been collected within the previous 3 weeks

,
Interventionparticipants (Number)
ADA positiveNAb positiveNO seroconversion
EU-approved Avastin®5013247
MB02 (Bevacizumab Biosimilar Drug)5310239

[back to top]

Progression-free Survival (PFS)

Progression-free survival was defined as the time from randomization to subsequent confirmed progression per RECIST version 1.1, or death (whichever occurred first), measured in weeks and months. For PFS assessment clinical progression (i.e., treatment discontinuation due to progression of disease) was also considered as an event. (NCT03296163)
Timeframe: At Week 52 from randomisation

Interventionweeks (Median)
MB02 (Bevacizumab Biosimilar Drug)36.0
EU-approved Avastin®37.3

[back to top]

Objective Response Rate (ORR) at Week 18

"Objective response rate was assigned for a subject if the subject displayed either complete response (CR) or partial response (PR) per RECIST version 1.1 at Week 18, as assessed by independent radiological review committee (IRC).~Overall Response (OR) = CR + PR." (NCT03296163)
Timeframe: 18 weeks from randomisation

InterventionPercentage of participants (Number)
MB02 (Bevacizumab Biosimilar Drug)40.3
EU-approved Avastin®44.6

[back to top]

Overall Survival (OS)

Overall survival was defined as the time from randomization to subsequent death, measured in weeks and months. (NCT03296163)
Timeframe: At Week 52 from randomisation

Interventionweeks (Median)
MB02 (Bevacizumab Biosimilar Drug)NA
EU-approved Avastin®NA

[back to top]

Number of Cycles of Chemotherapy Administered

To evaluate the number of cycles low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the number of cycles of chemotherapy administered. (NCT03301350)
Timeframe: Week 12 to week 18 to account for possible delays

InterventionParticipants (Count of Participants)
4 complete cyclesLess than 1 cycle
Neoadjuvant Chemotherapy253

[back to top]

Delays of Administered Chemotherapy

To evaluate the delays of low dose weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the delays of chemotherapy administered. (NCT03301350)
Timeframe: Week 12 to week 18 to account for possible delays

InterventionParticipants (Count of Participants)
Participants with no delaysParticipants with single 1 week delayParticipants with single 2 week delayParticipants with more than 1 delay
Neoadjuvant Chemotherapy12734

[back to top]

Total Dose of Chemotherapy Administered

To evaluate the total dose of weekly Carboplatin/Paclitaxel regimen administered. Simple descriptive statistics will be used to describe the dose amount of chemotherapy administered. (NCT03301350)
Timeframe: Week 12 to week 18 to account for possible delays

Interventiondoses administered (Number)
Carboplatin dose AUC of 2.0 - full dosepaclitaxel dose: 80 mg/m2 - full doseCarboplatin reduced dose AUC 1.6Carboplatin reduced dose AUC 1.5Paclitaxel - reduced dose
Neoadjuvant Chemotherapy28527915223

[back to top]

Number and Percentage of Participants With Pathologic Complete Response (pCR) Rate

pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy. pCR will be assessed according to RECIST 1.1 criteria. The point estimate of the primary efficacy endpoint pCR and its exact 95% confidence intervals (CI) will be calculated. In evaluating pCR, subjects with missing data will be considered non-responders. (NCT03301350)
Timeframe: Up to 2 years

InterventionParticipants (Count of Participants)
Neoadjuvant Chemotherapy8

[back to top] [back to top]

Part B: Vz of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=10Cycle 5, n=8Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel5.36617.26278.0529

[back to top]

Part B: Vss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=10Cycle 5, n=8Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel5.18936.77017.4351

[back to top]

Part B: Tmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Cycle 4, n=10Cycle 5, n=9Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel0.5751.5000.542

[back to top]

Part B: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionParticipants (Count of Participants)
Non-Serious TEAEsSTEAEsAESIs
Part B: TSR-042 and Carboplatin-paclitaxel1490

[back to top]

Part B: Ctau,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=9Cycle 5, n=8Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel67.244459.300057.4833

[back to top]

Part B: Cmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=10Cycle 5, n=9Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel225.8000421.1111446.6667

[back to top]

Part B: CL of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Cycle 4, n=10Cycle 5, n=8Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel0.00980.00820.0092

[back to top]

Part B: AUCss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 4, n=10Cycle 5, n=8Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel55073.0926130694.9752117033.3612

[back to top]

Part B: AUC0-t of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 1, n=14Cycle 4, n=10Cycle 5, n=9Cycle 11, n=6
Part B: TSR-042 and Carboplatin-paclitaxel28097.984654730.0053124309.5455117030.4081

[back to top]

Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 1, n=1,0Cycle 2, n=8,2
Part A: TSR-042 and Niraparib 200 mg QD380.1478716.1418

[back to top]

Part A: Volume of Distribution After Oral Administration (Vz/F) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 2, n=8,2
Part A: TSR-042 and Niraparib 300 mg QD487.8826

[back to top]

Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=5,2Cycle 5, n=8,1Cycle 11, n=4,0
Part A: TSR-042 and Niraparib 200 mg QD5.69256.88117.4795

[back to top]

Part A: Volume of Distribution After Intravenous Administration (Vz) of of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=5,2Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD10.39846.3070

[back to top]

Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=5,2Cycle 5, n=8,1Cycle 11, n=4,0
Part A: TSR-042 and Niraparib 200 mg QD5.56476.65807.3107

[back to top]

Part A: Volume of Distribution After Intravenous Administration (Vss) of of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=5,2Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD9.86805.9659

[back to top]

Part A: Tmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Cycle 4, n=9,4Cycle 5, n=8,1Cycle 11, n=5,0
Part A: TSR-042 and Niraparib 200 mg QD1.5000.6250.567

[back to top]

Part A: Tmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Cycle 4, n=9,4Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD1.3002.783

[back to top]

Part A: Tmax at Steady State (Tmax,ss) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Cycle 2, n=10,3Cycle 5, n=7,0Cycle 11, n=2,0
Part A: TSR-042 and Niraparib 200 mg QD4.0082.0001.817

[back to top]

Part A: Tmax at Steady State (Tmax,ss) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Cycle 2, n=10,3
Part A: TSR-042 and Niraparib 300 mg QD2.250

[back to top]

Part A: Number of Participants With Non-serious Treatment-emergent Adverse Events (TEAEs), Serious TEAEs (STEAEs) and Adverse Events of Special Interest (AESIs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported. (NCT03307785)
Timeframe: Up to 28.5 months

,
InterventionParticipants (Count of Participants)
Non-serious TEAEsSTEAEsAESIs
Part A: TSR-042 and Niraparib 200 mg QD16111
Part A: TSR-042 and Niraparib 300 mg QD641

[back to top]

Part A: Ctau,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=8,1Cycle 5, n=8,1Cycle 11, n=4,0
Part A: TSR-042 and Niraparib 200 mg QD77.362568.550093.8000

[back to top]

Part A: Ctau,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=8,1Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD63.300071.2000

[back to top]

Part A: Ctau at Steady State (Ctau,ss) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

,
InterventionMicrogram per milliliter (Mean)
Cycle 2, n=11,6
Part A: TSR-042 and Niraparib 200 mg QD0.507900
Part A: TSR-042 and Niraparib 300 mg QD0.622000

[back to top]

Part A: Cmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=9,4Cycle 5, n=8,1Cycle 11, n=5,0
Part A: TSR-042 and Niraparib 200 mg QD222.5556393.8750405.4000

[back to top]

Part A: Cmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=9,4Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD178.5000319.0000

[back to top]

Part A: Cmax at Steady State (Cmax,ss) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 2, n=10,3Cycle 5, n=7,0Cycle 11, n=2,0
Part A: TSR-042 and Niraparib 200 mg QD0.9259000.8390710.768000

[back to top]

Part A: Cmax at Steady State (Cmax,ss) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 2, n=10,3
Part A: TSR-042 and Niraparib 300 mg QD1.706667

[back to top]

Part A: Clearance After Oral Administration (CL/F) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Cycle 1, n=1,0Cycle 2, n=8,2
Part A: TSR-042 and Niraparib 200 mg QD28.563816.6295

[back to top]

Part A: Clearance After Oral Administration (CL/F) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Cycle 2, n=8,2
Part A: TSR-042 and Niraparib 300 mg QD10.2833

[back to top]

Part A: Clearance After Intravenous Administration (CL) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Cycle 4, n=7,2Cycle 5, n=8,1Cycle 11, n=4,0
Part A: TSR-042 and Niraparib 200 mg QD0.00900.00810.0072

[back to top]

Part A: Clearance After Intravenous Administration (CL) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Cycle 4, n=7,2Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD0.01100.0071

[back to top]

Part A: AUCss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 4, n=7,2Cycle 5, n=8,1Cycle 11, n=4,0
Part A: TSR-042 and Niraparib 200 mg QD58598.5076135171.2753151575.3645

[back to top]

Part A: AUCss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 4, n=7,2Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD46122.3924141306.3782

[back to top]

Part A: AUC(0-t) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 1, n=16,6Cycle 4, n=9,4Cycle 5, n=8,1Cycle 11, n=5,0
Part A: TSR-042 and Niraparib 200 mg QD26827.770355408.3992137108.2574139591.8834

[back to top]

Part A: AUC(0-t) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 1, n=16,6Cycle 4, n=9,4Cycle 5, n=8,1
Part A: TSR-042 and Niraparib 300 mg QD29420.834729311.8182141328.9288

[back to top]

Part F: Vz of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Vz of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Vss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Vss of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Tmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Tmax,ss of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Tmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Tmax of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Objective Response Rate

Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. (NCT03307785)
Timeframe: Up to 3.5 months

InterventionPercentage of participants (Number)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexed0

[back to top]

Part F: Number of Participants With Positive Anti-TSR-042 Antibodies

Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). (NCT03307785)
Timeframe: Up to 3.5 months

InterventionParticipants (Count of Participants)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Number of Participants With Positive Anti-TSR-022 Antibodies

Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-022. The presence of anti-TSR-022 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). (NCT03307785)
Timeframe: Up to 3.5 months

InterventionParticipants (Count of Participants)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Number of Participants With DLT

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D. (NCT03307785)
Timeframe: 21 days

InterventionParticipants (Count of Participants)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexed0

[back to top]

Part F: Duration of Response

Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. (NCT03307785)
Timeframe: Up to 3.5 months

InterventionMonths (Median)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Disease Control Rate

Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1. (NCT03307785)
Timeframe: Up to 3.5 months

InterventionPercentage of participants (Number)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexed100

[back to top]

Part F: Ctau,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Ctau,ss of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part C: AUCss of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab21.4926
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab26.5006

[back to top]

Part C: AUC(0-infinity) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part C: TSR-042, Niraparib 200 mg QD and BevacizumabNA
Part C: TSR-042, Niraparib 300 mg QD and BevacizumabNA

[back to top]

Part C: AUC(0-infinity) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part C: TSR-042, Niraparib 200 mg QD and BevacizumabNA
Part C: TSR-042, Niraparib 300 mg QD and BevacizumabNA

[back to top]

Part C: Cmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab138.6667
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab158.4857

[back to top]

Part C: Ctau of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab0.161233
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab0.478714

[back to top]

Part C: Ctau of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab37.2750
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab28.7500

[back to top]

Part C: Disease Control Rate

Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1. (NCT03307785)
Timeframe: Up to 22.5 months

InterventionPercentage of participants (Number)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab83.3
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab85.7

[back to top]

Part C: Number of Participants With DLT

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D. (NCT03307785)
Timeframe: 21 days

InterventionParticipants (Count of Participants)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab1
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab1

[back to top]

Part C: Number of Participants With Positive Anti-TSR-042 Antibodies

Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). (NCT03307785)
Timeframe: Up to 22.5 months

InterventionParticipants (Count of Participants)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab0
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab0

[back to top]

Part C: Objective Response Rate

Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. (NCT03307785)
Timeframe: Up to 22.5 months

InterventionPercentage of participants (Number)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab50.0
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab14.3

[back to top]

Part C: Progression-free Survival

Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. (NCT03307785)
Timeframe: Up to 22.5 months

InterventionMonths (Median)
Part C: TSR-042, Niraparib 200 mg QD and BevacizumabNA
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab9.1

[back to top]

Part C: Tmax of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab3.975
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab4.050

[back to top]

Part C: Tmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab1.200
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab0.583

[back to top]

Part D: AUC(0-infinity) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part D: TSR-042, Carboplatin-paclitaxel and BevacizumabNA

[back to top]

Part D: Cmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab188.5000

[back to top]

Part D: Ctau of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab36.5250

[back to top]

Part D: Disease Control Rate

Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1. (NCT03307785)
Timeframe: Up to 9.5 months

InterventionPercentage of participants (Number)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab83.3

[back to top]

Part B: Tmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part B: TSR-042 and Carboplatin-paclitaxel1.000

[back to top]

Part B: Progression-free Survival

Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionMonths (Median)
Part B: TSR-042 and Carboplatin-paclitaxel17.6

[back to top]

Part B: Objective Response Rate

Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionPercentage of participants (Number)
Part B: TSR-042 and Carboplatin-paclitaxel42.9

[back to top]

Part D: Number of Participants With DLT

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D. (NCT03307785)
Timeframe: 21 days

InterventionParticipants (Count of Participants)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab0

[back to top]

Part D: Number of Participants With Positive Anti-TSR-042 Antibodies

Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). (NCT03307785)
Timeframe: Up to 9.5 months

InterventionParticipants (Count of Participants)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab0

[back to top]

Part B: Number of Participants With Positive Anti-TSR-042 Antibodies

Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). (NCT03307785)
Timeframe: Up to 28.5 months

InterventionParticipants (Count of Participants)
Part B: TSR-042 and Carboplatin-paclitaxel4

[back to top]

Part B: Number of Participants With DLT

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D. (NCT03307785)
Timeframe: 21 days

InterventionParticipants (Count of Participants)
Part B: TSR-042 and Carboplatin-paclitaxel1

[back to top]

Part B: Disease Control Rate

Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionPercentage of participants (Number)
Part B: TSR-042 and Carboplatin-paclitaxel57.1

[back to top]

Part B: Ctau of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part B: TSR-042 and Carboplatin-paclitaxel33.9778

[back to top]

Part B: Cmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part B: TSR-042 and Carboplatin-paclitaxel148.2000

[back to top]

Part B: AUC(0-infinity) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part B: TSR-042 and Carboplatin-paclitaxelNA

[back to top]

Part A: Tmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part A: TSR-042 and Niraparib 200 mg QD0.817
Part A: TSR-042 and Niraparib 300 mg QD1.750

[back to top]

Part A: Time to Reach Maximum Plasma Concentration (Tmax) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part A: TSR-042 and Niraparib 200 mg QD2.250
Part A: TSR-042 and Niraparib 300 mg QD4.083

[back to top]

Part A: Progression-free Survival

Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionMonths (Median)
Part A: TSR-042 and Niraparib 200 mg QD6.2
Part A: TSR-042 and Niraparib 300 mg QD2.8

[back to top]

Part A: Observed Concentration at the End of the Dosing Interval (Ctau) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part A: TSR-042 and Niraparib 200 mg QD0.191953
Part A: TSR-042 and Niraparib 300 mg QD0.342333

[back to top]

Part A: Objective Response Rate

Objective Response Rate is defined as the percentage of participants who achieved confirmed complete response (CR) or partial response (PR), evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 millimeters (mm) in the short axis. PR=At least a 30 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionPercentage of participants (Number)
Part A: TSR-042 and Niraparib 200 mg QD25.0
Part A: TSR-042 and Niraparib 300 mg QD0

[back to top]

Part A: Number of Participants With Positive Anti-TSR-042 Antibodies

Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). Anti-drug Antibody Population consisted of all participants who received at least 1 dose of study treatment and had provided a pre-dose blood sample and at least 1 post-dose blood sample at or after 96 hours. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionParticipants (Count of Participants)
Part A: TSR-042 and Niraparib 200 mg QD0
Part A: TSR-042 and Niraparib 300 mg QD0

[back to top]

Part A: Number of Participants With Dose-limiting Toxicity (DLT)

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of adverse event(AE) onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish recommended phase 2 dose (RP2D). (NCT03307785)
Timeframe: 21 days

InterventionParticipants (Count of Participants)
Part A: TSR-042 and Niraparib 200 mg QD2
Part A: TSR-042 and Niraparib 300 mg QD0

[back to top]

Part A: Maximum Observed Plasma (Cmax) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part A: TSR-042 and Niraparib 200 mg QD0.460600
Part A: TSR-042 and Niraparib 300 mg QD0.625667

[back to top]

Part A: Duration of Response

Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionMonths (Median)
Part A: TSR-042 and Niraparib 200 mg QD7.59
Part A: TSR-042 and Niraparib 300 mg QDNA

[back to top]

Part A: Disease Control Rate

Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or stable disease (SD) per RECIST version 1.1. (NCT03307785)
Timeframe: Up to 28.5 months

InterventionPercentage of participants (Number)
Part A: TSR-042 and Niraparib 200 mg QD43.8
Part A: TSR-042 and Niraparib 300 mg QD33.3

[back to top]

Part A: Ctau of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part A: TSR-042 and Niraparib 200 mg QD33.6000
Part A: TSR-042 and Niraparib 300 mg QD29.8000

[back to top]

Part A: Cmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part A: TSR-042 and Niraparib 200 mg QD158.6875
Part A: TSR-042 and Niraparib 300 mg QD138.9167

[back to top]

Part A: AUC(0-infinity) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part A: TSR-042 and Niraparib 200 mg QDNA
Part A: TSR-042 and Niraparib 300 mg QDNA

[back to top]

Part A: AUC at Steady State (AUCss) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part A: TSR-042 and Niraparib 200 mg QD16.3481
Part A: TSR-042 and Niraparib 300 mg QD29.4312

[back to top]

Part A: Area Under the Plasma Concentration From Time Zero to Infinity (AUC[0-infinity]) of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part A: TSR-042 and Niraparib 200 mg QDNA
Part A: TSR-042 and Niraparib 300 mg QDNA

[back to top]

Part D: Objective Response Rate

Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. (NCT03307785)
Timeframe: Up to 9.5 months

InterventionPercentage of participants (Number)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab50.0

[back to top]

Part D: Progression-free Survival

Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. (NCT03307785)
Timeframe: Up to 9.5 months

InterventionMonths (Median)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab7.6

[back to top]

Part D: Tmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab1.250

[back to top]

Part E: AUC(0-infinity) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: AUC0-t of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: AUCss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: CL of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Cmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Cmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Ctau of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Ctau,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Disease Control Rate

Disease Control Rate is defined as the percentage of participants who had achieved CR, PR, or SD per RECIST version 1.1. (NCT03307785)
Timeframe: Up to 4.4 months

InterventionPercentage of participants (Number)
Part E: TSR-042 and Carboplatin-pemetrexed0

[back to top]

Part E: Duration of Response

Duration of response is defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression by RECIST version 1.1 or death by any cause. (NCT03307785)
Timeframe: Up to 4.4 months

InterventionMonths (Median)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Number of Participants With DLT

An event was considered a DLT if it occurred within the first 21 days of treatment, and met one of following DLT criteria:hematologic toxicity- Grade4 thrombocytopenia persists for >=7 days from the time of AE onset, Grade 4 neutropenia, Grade 4 or Grade 3 febrile neutropenia persists for >=7 days, Grade4 or Grade3 anemia requiring blood transfusion, Grade 3 thrombocytopenia associated with clinically significant bleeding, Grade 3 neutropenia associated with infection as described in CTCAE version 4.0, drug related Grade 3 or 4 non-hematologic toxicity, drug related Grade 3 or 4 nonhematologic laboratory abnormality if any of the following also occur: abnormality leads to hospitalization and abnormality persists for >=7 days from the time of AE onset; drug related toxicity leading to prolonged delay (>2 weeks) in initiating Cycle 2. DLTs were collected during first cycle to establish RP2D. (NCT03307785)
Timeframe: 21 days

InterventionParticipants (Count of Participants)
Part E: TSR-042 and Carboplatin-pemetrexed0

[back to top]

Part E: Number of Participants With Positive Anti-TSR-042 Antibodies

Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to TSR-042. The presence of anti-TSR-042 antibodies were assessed using a tiered approach using electrochemiluminescence (that is, screening, confirmation, titer, and neutralizing antibody assay). (NCT03307785)
Timeframe: Up to 4.4 months

InterventionParticipants (Count of Participants)
Part E: TSR-042 and Carboplatin-pemetrexed0

[back to top]

Part E: Objective Response Rate

Objective Response Rate is defined as the percentage of participants who achieved confirmed CR or PR, evaluated using RECIST version 1.1 based on Investigator assessment; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be <10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. (NCT03307785)
Timeframe: Up to 4.4 months

InterventionPercentage of participants (Number)
Part E: TSR-042 and Carboplatin-pemetrexed0

[back to top]

Part C: Cmax of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab0.243667
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab0.891571

[back to top]

Part E: Progression-free Survival

Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. (NCT03307785)
Timeframe: Up to 4.4 months

InterventionMonths (Median)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Tmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Tmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose (each cycle was 21 days)

InterventionHours (Median)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Vss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose (each cycle was 21 days)

InterventionLiter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part E: Vz of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose (each cycle was 21 days)

InterventionLiter (Mean)
Part E: TSR-042 and Carboplatin-pemetrexedNA

[back to top]

Part F: AUC(0-infinity) of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Progression-free Survival

Progression-free Survival is defined as the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. PD is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. (NCT03307785)
Timeframe: Up to 3.5 months

InterventionMonths (Median)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: AUC(0-infinity) of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Geometric Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: AUC0-t of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: AUC0-t of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: AUCss of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part A: Area Under the Plasma Concentration From Time Zero to t (AUC[0-t]) of Niraparib

Blood samples were collected at indicated time points. Pharmacokinetic (PK) parameters of niraparib were calculated using non-compartmental methods. PK population consisted of all participants who received at least 1 dose of study treatment and had at least 1 PK sample. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

,
InterventionHours*microgram per milliliter (Mean)
Cycle 1, n=15,6Cycle 2, n=10,3
Part A: TSR-042 and Niraparib 200 mg QD6.043014.9172
Part A: TSR-042 and Niraparib 300 mg QD7.834129.3024

[back to top]

Part F: AUCss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: CL of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: CL of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose; Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Cmax of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168 and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Cmax of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Cmax,ss of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Cmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose; Cycle 5: Pre-dose, 0.5, 2, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Ctau of TSR-022

Blood samples were collected at indicated time points. PK parameters of TSR-022 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Ctau of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 1: Pre-dose, 0.5, 1, 2, 3, 24, 48, 96, 168, and 336 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexedNA

[back to top]

Part F: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported. (NCT03307785)
Timeframe: Up to 3.5 months

InterventionParticipants (Count of Participants)
Non-serious TEAEsSTEAEsAESIs
Part F: TSR-042, TSR-022, and Carboplatin-pemetrexed100

[back to top]

Part E: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported. (NCT03307785)
Timeframe: Up to 4.4 months

InterventionParticipants (Count of Participants)
Non-serious TEAEsSTEAEsAESIs
Part E: TSR-042 and Carboplatin-pemetrexed220

[back to top]

Part D: Vz of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=5Cycle 5, n=5Cycle 11, n=3
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab5.49556.15429.8356

[back to top]

Part D: Vss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter (Mean)
Cycle 4, n=5Cycle 5, n=5Cycle 11, n=3
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab5.14935.63998.0614

[back to top]

Part D: Tmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours (Median)
Cycle 4, n=5Cycle 5, n=5Cycle 11, n=4
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab0.5000.5500.500

[back to top]

Part D: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported. (NCT03307785)
Timeframe: Up to 9.5 months

InterventionParticipants (Count of Participants)
Non-serious TEAEsSTEAEsAESIs
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab630

[back to top]

Part D: Ctau,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=5Cycle 5, n=5Cycle 11, n=3
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab53.520048.080043.3000

[back to top]

Part D: Cmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionMicrogram per milliliter (Mean)
Cycle 4, n=5Cycle 5, n=5Cycle 11, n=4
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab256.8000416.0000429.7500

[back to top]

Part D: CL of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionLiter per hour (Mean)
Cycle 4, n=5Cycle 5, n=5Cycle 11, n=3
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab0.01020.00870.0104

[back to top]

Part D: AUCss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 4, n=5Cycle 5, n=5Cycle 11, n=3
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab51140.4410118845.392896800.1534

[back to top]

Part D: AUC0-t of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

InterventionHours*microgram per milliliter (Mean)
Cycle 1, n=6Cycle 4, n=5Cycle 5, n=5Cycle 11, n=4
Part D: TSR-042, Carboplatin-paclitaxel and Bevacizumab32819.540152409.0255119847.099977794.6422

[back to top]

Part C: Vz/F of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

,
InterventionLiter (Mean)
Cycle 2, n=2,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab551.4003
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab559.3634

[back to top]

Part C: Vz of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionLiter (Mean)
Cycle 4, n=5,5Cycle 5, n=4,6Cycle 11, n=4,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab6.64626.16989.6347
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab5.89225.20668.5098

[back to top]

Part C: Vss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionLiter (Mean)
Cycle 4, n=5,5Cycle 5, n=4,6Cycle 11, n=4,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab6.45676.24058.9478
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab5.51774.80357.7750

[back to top]

Part C: Tmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionHours (Median)
Cycle 4, n=5,7Cycle 5, n=5,6Cycle 11, n=4,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab1.5172.0832.000
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab0.6170.8252.417

[back to top]

Part C: Tmax,ss of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

,
InterventionHours (Median)
Cycle 2, n=4,4Cycle 5, n=4,3Cycle 11, n=3,1
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab4.9502.1582.000
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab3.9581.9672.083

[back to top]

Part C: Number of Participants With Non-serious TEAEs, STEAEs and AESIs

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. An SAE is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement. TEAE is any event that was not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Number of participants with TEAEs, SAEs and AESIs are reported. (NCT03307785)
Timeframe: Up to 22.5 months

,
InterventionParticipants (Count of Participants)
Non-serious TEAEsSTEAEsAESIs
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab530
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab730

[back to top]

Part C: Ctau,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionMicrogram per milliliter (Mean)
Cycle 4, n=4,6Cycle 5, n=5,6Cycle 11, n=3,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab70.425082.9800105.4667
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab64.266753.150060.9500

[back to top]

Part C: Ctau,ss of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

,
InterventionMicrogram per milliliter (Mean)
Cycle 2, n=5,4
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab0.484000
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab1.094250

[back to top]

Part C: Cmax,ss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionMicrogram per milliliter (Mean)
Cycle 4, n=5,7Cycle 5, n=5,6Cycle 11, n=4,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab234.4000325.2000349.7500
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab227.1429417.3333321.0000

[back to top]

Part C: Cmax,ss of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose; Cycles 5 and 11: Pre-dose, 2 hours post-dose (each cycle was 21 days)

,
InterventionMicrogram per milliliter (Mean)
Cycle 2, n=4,4Cycle 5, n=4,3Cycle 11, n=3,1
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab0.8545000.7097500.468333
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab1.4047501.0736670.638000

[back to top]

Part C: CL/F of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

,
InterventionLiter per hour (Mean)
Cycle 2, n=2,4
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab10.3777
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab14.4947

[back to top]

Part C: CL of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionLiter per hour (Mean)
Cycle 4, n=5,5Cycle 5, n=5,6Cycle 11, n=4,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab0.01000.00820.0079
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab0.01040.00820.0086

[back to top]

Part C: AUCss of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycle 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionHours*microgram per milliliter (Mean)
Cycle 4, n=5,5Cycle 5, n=5,6Cycle 11, n=4,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab55974.4268137399.5881147907.5379
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab50924.1510131288.0291119189.5905

[back to top]

Part C: AUC0-t of TSR-042

Blood samples were collected at indicated time points. PK parameters of TSR-042 were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 4: Pre-dose, 0.5, 2, 24, 96, 168, 336 and 504 hours post-dose; Cycles 5 and 11: Pre-dose, 0.5, 2, 24, 96, 168, 336, 504 and 1008 hours post-dose (each cycle was 21 days)

,
InterventionHours*microgram per milliliter (Mean)
Cycle 1, n=6,7Cycle 4, n=5,7Cycle 5, n=5,6Cycle 11, n=4,2
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab29830.654254268.1379137777.3188143070.3093
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab26311.178949198.8237131281.9046119161.8795

[back to top]

Part C: AUC0-t of Niraparib

Blood samples were collected at indicated time points. PK parameters of niraparib were calculated using non-compartmental methods. (NCT03307785)
Timeframe: Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8 and 24 hours post-dose (each cycle was 21 days)

,
InterventionHours*microgram per milliliter (Mean)
Cycle 1, n=6,7Cycle 2, n=4,4
Part C: TSR-042, Niraparib 200 mg QD and Bevacizumab3.451314.7473
Part C: TSR-042, Niraparib 300 mg QD and Bevacizumab11.360124.9691

[back to top]

Duration of Response (DOR) as Per RECIST v 1.1 by Investigator Assessment

DOR was defined as time from first documentation of objective response (confirmed CR or PR) to the date of first PD documentation or death due to any cause, whichever occurs first. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (<)10 millimeter(mm). PR: >=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. Median DOR was not derived for < 5 participants. (NCT03317496)
Timeframe: From date of first documented response to date of first documented PD or death due to any cause, whichever occurred first (maximum up to 5 years approximately)

InterventionMonths (Median)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/CarboplatinNA
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin9.6
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/CarboplatinNA
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/CisplatinNA

[back to top] [back to top]

Overall Survival (OS)

OS was defined as the time from the first dose of study treatment to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact. The median duration of OS was not derived for less than (<) 10 participants. (NCT03317496)
Timeframe: From first dose of study treatment until death due to any cause (maximum up to 5 years approximately)

InterventionMonths (Median)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/CarboplatinNA
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin18.1
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/CarboplatinNA
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin15.1

[back to top]

Serum Concentration of Avelumab

The lower limit of quantification (LLOQ) for avelumab was 0.2 micrograms per milliliter. Pharmacokinetic concentration analysis set was subset of safety analysis set and included participants who had at least one concentration measurement for avelumab or other study drugs which they were assigned to receive. Treatment groups with same dose and administration frequency were combined as pre-specified in reporting and analysis plan. (NCT03317496)
Timeframe: Pre-dose, 1 hour post-dose on Day 1 of Cycle 1, 2, 3, 6, 10, 14; 336 hours post-dose on Day 15 of Cycle 1, 2, 3 (each cycle of 21 days)

,,,
InterventionMicrograms per milliliter (Geometric Mean)
Cycle 1/Day 1- 1 hourCycle 1/Day 15- 336 hoursCycle 2/Day 1- pre-doseCycle 2/Day 1- 1 hourCycle 2/Day 15- 336 hoursCycle 3/Day 1- pre-doseCycle 3/Day 1- 1 hourCycle 3/Day 15- 336 hoursCycle 6/Day 1- pre-doseCycle 6/Day 1- 1 hourCycle 10/Day 1- pre-doseCycle 10/Day 1- 1 hourCycle 14/Day 1- pre-doseCycle 14/Day 1- 1 hour
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin284.116.514.328104.516.824.87893.8126.1710.86245.46.6206.04012.2429.05
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin172.29.5703.754197.013.555.651204.017.159.518208.38.695222.013.37216.6
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin173.312.324.780164.216.878.122147.019.4011.3892.539.523179.014.97215.3
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin300.214.715.013311.918.666.771296.822.5510.39344.018.55242.916.49402.2

[back to top]

Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v 4.03

AE was any untoward medical occurrence in a participant who received any study drug without regard to possibility of causal relationship. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. TEAEs were graded by the investigator using NCI CTCAE v 4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. In this outcome measure, number of participants with grade 3 or higher TEAEs were reported. (NCT03317496)
Timeframe: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

InterventionParticipants (Count of Participants)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin5
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin12
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin6
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin37

[back to top]

Number of Participants With Programmed Death-Ligand 1 (PD-L1) Expression

PD-L1 expression was determined using the Ventana PD-L1 SP263 IHC assay. PD-L1-positive status in UC cohorts was defined using an algorithm that combines assessments of PD-L1 staining on tumor and immune cells scored by pathologists and in NSCLC cohorts was defined as PD-L1 expression on >=1% of tumor cells. PD-L1 expression at baseline and on-treatment were reported in this outcome measure. (NCT03317496)
Timeframe: Baseline and Cycle 2 Day 8 (each cycle of 21 days)

,,,
InterventionParticipants (Count of Participants)
Baseline- Positive PD-L1Baseline- Negative PD-L1Baseline- Unknown PD-L1On-treatment (Cycle 2 Day 8)- Positive PD-L1On-treatment (Cycle 2 Day 8)- Negative PD-L1On-treatment (Cycle 2 Day 8)- Unknown PD-L1
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin141105
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin6702110
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin042024
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin281303632

[back to top]

Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment

OR: complete response(CR) or partial response(PR)determined by investigator according to RECIST v1.1 from date of first dose of study treatment until date of first documentation of progressive disease(PD),confirmed by repeat assessments performed no less than 4 weeks after first response. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (<)10 millimeter(mm). PR: >=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. (NCT03317496)
Timeframe: From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 3.5 years approximately)

InterventionPercentage of Participants (Number)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin50.0
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin53.8
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin33.3
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin39.0

[back to top]

Phase 1b Lead-in: Number of Participants With Dose-Limiting Toxicities (DLT)

DLTs=occurrence of any AEs attributable to study treatment in first 2 treatment cycles:Hematologic: grade(G)4 neutropenia lasting >7days;febrile neutropenia with body temperature >=38 degree Celsius for >1hour; G>=3 neutropenic infection(absolute neutrophil count <1.0*10^9/L),G>=3 thrombocytopenia (platelet count<50.0-25.0*10^9/L)with bleeding;G4 thrombocytopenia(PC<25.0*10^9/L),G4 anemia(life-threatening).Non-hematologic: any G4 toxicities;G3 toxicities persisting for >3days despite medical treatment(nausea,vomiting,diarrhea)except endocrinopathies controlled with hormonal therapy;ALT/AST >3*upper limit of normal(ULN)if normal at baseline or 2*Baseline(>ULN at baseline)with total bilirubin >2*ULN and alkaline phosphatase <2*ULN;G3 QTcF prolongation after correction of any reversible cause(electrolyte abnormalities/hypoxia).Delay of >=3weeks in scheduled administration/failure to deliver 75% of doses due to toxicities attributable to any study treatment. DLT-evaluable analysis set. (NCT03317496)
Timeframe: Day 1 up to Week 6 (first 2 treatment cycles; 1 cycle = 21 days)

InterventionParticipants (Count of Participants)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin0
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin1
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin0
Phase 1b Lead-in: Avelumab 1200mg+Gemcitabine/Cisplatin1

[back to top]

Progression Free Survival (PFS) as Per RECIST v 1.1 by Investigator Assessment

PFS was defined as the time from the date of first dose of study treatment to the date of the first documentation of PD per RECIST v1.1 or death due to any cause, whichever occurred first. PD: >=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm, appearance of one or more new lesions was considered PD. The median duration of PFS was not derived for less than (<) 10 participants. (NCT03317496)
Timeframe: From start of treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5 years approximately)

InterventionMonths (Median)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/CarboplatinNA
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin9.8
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/CarboplatinNA
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin5.4

[back to top]

Absolute Value of Tumor Mutational Burden (TMB) in Tumor Tissue

Mutational load within tumor tissue was defined as number per megabase of the genome, coding, base substitution, and indel mutations present in the sample. Mutational load was determined in whole blood samples using next generation deoxyribonucleic acid (DNA) sequencing followed by computational analysis. (NCT03317496)
Timeframe: Pre-dose on Day 1 of Cycle 1

InterventionMutations per megabase (Mean)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin4.3
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin2.8
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin4.4
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin2.5

[back to top]

Time-to-Tumor Response (TTR) as Per RECIST v 1.1 by Investigator Assessment

TTR was defined as the time from the date of first dose of study treatment to the first documentation of objective response (CR or PR) as assessed by investigator according to RECIST v 1.1. CR: disappearance of target and non-target lesions, with exception of nodal disease and normalization of tumor markers. All nodes, target and non-target must have short axis measures less than (<)10 millimeter(mm). PR: >=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. (NCT03317496)
Timeframe: From first dose of study treatment until first documentation of CR or PR (maximum up to 5 years approximately)

InterventionMonths (Median)
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin2.8
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin1.4
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin1.3
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin1.5

[back to top]

Number of Participants With Grade 3 or Higher Laboratory Abnormalities by CTCAE Grade

Participants with laboratory abnormalities of any Grade as per NCI CTCAE toxicity grading v4.03 were summarized:hematology(anemia,hemoglobin increased,lymphocyte count decreased,lymphocyte count increased, neutrophil count decreased,platelet count decreased and white blood cell decreased)and clinical chemistry(alanine aminotransferase increased,alkaline phosphatase,increased,aspartate,aminotransferase increased,blood bilirubin increased,cholesterol high,creatinine phosphokinase[cpk] increased,creatinine increased,gamma-glutamyl transferase[ggt] increased,hypercalcemia,hyperglycemia,hyperkalemia, hypermagnesemia,hypernatremia,hypertriglyceridemia,hypoalbuminemia,hypocalcemia,hypoglycemia,hypokalemia,hypomagnesemia,hyponatremia, hypophosphatemia,serum amylase increased and lipase increased).As per NCI CTCAE toxicity grading v4.03, Grade1=mild;Grade2=moderate;Grade3=severe;Grade4=life-threatening;Grade 5=death.Parameters with at least 1 participant with abnormal value are reported. (NCT03317496)
Timeframe: From screening up to 90 days after last dose of study drug (maximum up to 5 years approximately)

,,,
InterventionParticipants (Count of Participants)
ALANINE AMINOTRANSFERASE INCREASEDALKALINE PHOSPHATASE INCREASEDASPARTATE AMINOTRANSFERASE INCREASEDBLOOD BILIRUBIN INCREASEDCPK INCREASEDCREATININE INCREASEDGGT INCREASEDHYPERGLYCEMIAHYPERKALEMIAHYPOKALEMIAHYPONATREMIALIPASE INCREASEDSERUM AMYLASE INCREASEDHYPOPHOSPHATEMIAHYPOMAGNESEMIAHYPOCALCEMIAHYPERTRIGLYCERIDEMIAHYPERNATREMIAHYPERMAGNESEMIAHYPERCALCEMIAANEMIALYMPHOCYTE COUNT DECREASEDLYMPHOCYTE COUNT INCREASEDNEUTROPHIL COUNT DECREASEDPLATELET COUNT DECREASEDWHITE BLOOD CELL DECREASED
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin00000010001101000000010303
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin10110122102220003000550827
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin10100102010102020000230332
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin31201044254443212111671211116

[back to top]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs

Adverse event (AE) was any untoward medical occurrence in a participants who received any study drug without regard to possibility of causal relationship. Serious adverse event was any untoward medical occurrence that at any dose resulted in any of following outcomes/deemed significant for any other reason: death; initial /prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect. TEAEs were those events with onset dates occurring during the on-treatment period. On-treatment period was defined as time from first dose of any study treatment and up to 30 days after last dose or start day of new anti-cancer drug therapy minus 1 day, whichever occurred first. (NCT03317496)
Timeframe: From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5 years approximately)

,,,
InterventionParticipants (Count of Participants)
TEAEsSerious TEAEs
Phase 1b Lead-in: Avelumab 1200 mg + Pemetrexed/Carboplatin65
Phase 1b Lead-in: Avelumab 800 mg + Gemcitabine/Cisplatin139
Phase 1b Lead-in: Avelumab 800 mg + Pemetrexed/Carboplatin63
Phase 1b Lead-in+Phase 2:Avelumab 1200mg+Gemcitabine/Cisplatin4020

[back to top]

Number of Non-cardiac Toxicities

The frequency of adverse events categorized using CTCAE v4.03 (NCT03329378)
Timeframe: 2 years

Interventionevents (Number)
ddACTHP63
TCHP120

[back to top]

Number of Participants With Pathologic Complete Response (pCR)

Pathologic complete response (pCR) defined as the absence of any residual invasive cancer on hematoxylin and eosin evaluation of the resected breast specimen and all sampled ipsilateral lymph nodes following completion of neoadjuvant systemic therapy. (NCT03329378)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
ddACTHP1
TCHP4

[back to top]

Number of Participants With Breast Conservation

"Number of participants with breast-conserving surgery for patients for whom mastectomy was planned before treatment. It would be based on surgical opinion at time of surgery if the tumor was appropriately downstaged to perform breast conserving surgery on patients previously recommended to have a mastectomy." (NCT03329378)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
ddACTHP0
TCHP0

[back to top]

Number of Participants Alive at the End of the Study

Overall Survival - Number of participants alive at the end of the study. (NCT03329378)
Timeframe: 2 years

InterventionParticipants (Count of Participants)
ddACTHP2
TCHP5

[back to top]

Number of Cardiac Toxicity Events

"Determination of cardiac toxicity as measured by LVEF, longitudinal strain and troponin.~Left ventricular ejection fraction (LVEF) measurement of amount of blood being pumped out of the left ventricle of the heart with each contraction.~Peak systolic longitudinal strain is calculated by averaging the values of peak systolic strain in the basal, mid and apical segments of the LV in 4-, 3- and 2-chamber views on echocardiograms. A value of <-18% or a >15% decline in strain from patient's baseline value will be used as a cut-off value.~A value of troponin I > 0.08 ng/ml will be considered elevated." (NCT03329378)
Timeframe: 2 years

Interventionevents (Number)
ddACTHP2
TCHP2

[back to top]

Overall Response Rate

"The primary efficacy endpoint is ORR at Week 18 (ORR18) based on tumor response evaluated according to RECIST 1.1 as assessed by CIR. Each patient will be assigned to one of the following RECIST 1.1 categories based on independent CIR, irrespective of protocol deviations or missing data:~CR: complete response. PR: partial response. SD: stable disease. PD: progressive disease. NE: not evaluable (insufficient data)" (NCT03329911)
Timeframe: Week 18

InterventionParticipants (Count of Participants)
EU Avastin®156
BAT1706145

[back to top]

Part A: Change From Time-matched Baseline in QRS After Pevonedistat Administration

Change from time-matched baseline in QRS was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. (NCT03330106)
Timeframe: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A

,
Interventionmilliseconds (Least Squares Mean)
Predose1 Hour Postdose2 Hours Postdose3 Hours Postdose4 Hours Postdose6 Hours Postdose9 Hours Postdose11 Hours Postdose24 Hours Postdose
Pevonedistat 25 mg/m^2-0.4591.447-0.2120.138-1.068-0.192-0.791-0.551-0.946
Pevonedistat 50 mg/m^2-0.4820.850-0.0430.184-0.241-0.319-0.221-0.769-0.470

[back to top]

Part A: Change From Time-matched Baseline in PR After Pevonedistat Administration

Change from time-matched baseline in PR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. (NCT03330106)
Timeframe: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A

,
Interventionmilliseconds (Least Squares Mean)
Predose1 Hour Postdose2 Hours Postdose3 Hours Postdose4 Hours Postdose6 Hours Postdose9 Hours Postdose11 Hours Postdose24 Hours Postdose
Pevonedistat 25 mg/m^2-2.8941.152-0.090-1.557-3.406-4.665-4.499-3.018-5.245
Pevonedistat 50 mg/m^2-1.2203.3601.514-0.167-1.802-4.463-3.608-2.333-6.499

[back to top]

Part A: Change From Time-matched Baseline in Individual Corrected QT Interval (QTcI) After Pevonedistat Administration

Change from time-matched baseline in QTcI was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. (NCT03330106)
Timeframe: Predose, and at multiple time points up to 24 hours post dose on Day 1 or Day 8 in Part A

,
Interventionmilliseconds (Least Squares Mean)
Predose1 Hour Postdose2 Hours Postdose3 Hours Postdose4 Hours Postdose6 Hours Postdose9 Hours Postdose11 Hours Postdose24 Hours Postdose
Pevonedistat 25 mg/m^22.0993.5801.4773.0743.8162.143-1.4190.020-1.897
Pevonedistat 50 mg/m^2-1.884-0.206-0.0991.8771.3050.198-2.482-5.250-3.105

[back to top]

Part A: Change From Time-matched Baseline in Heart Rate (HR) After Pevonedistat Administration

Change from time-matched baseline in HR was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. ANOVA was used for the analysis. (NCT03330106)
Timeframe: Predose, and at multiple time points post dose up to 24 hours on Day 1 or Day 8 in Part A

,
Interventionbeats per minute (bpm) (Least Squares Mean)
Predose1 Hour Postdose2 Hours Postdose3 Hours Postdose4 Hours Postdose6 Hours Postdose9 Hours Postdose11 Hours Postdose24 Hours Postdose
Pevonedistat 25 mg/m^20.602-2.068-1.812-0.993-0.2792.7122.5452.7944.432
Pevonedistat 50 mg/m^20.981-1.595-0.5561.9292.7366.4117.1347.5117.609

[back to top]

Part A: Change From Time-matched Baseline in Fridericia-corrected QT Interval (QTcF) After Pevonedistat Administration

Change from time-matched baseline in QTcF was assessed following a single intravenous dose administration of pevonedistat at 25 and 50 mg/m^2 and was analysed by dose. Some participants were treated with pevonedistat 25 mg/m^2 or 50 mg/m^2 on Day 1 while others received treatment on Day 8. Data is reported at pre-dose and at multiple timepoints (1, 2, 3, 4, 6, 9, 11 and 24 hours) postdose up to Day 8 in Part A. Analysis of variance (ANOVA) was used for the analysis. (NCT03330106)
Timeframe: Baseline up to Day 8

,
Interventionmilliseconds (Least Squares Mean)
Predose1 Hour Postdose2 Hours Postdose3 Hours Postdose4 Hours Postdose6 Hours Postdose9 Hours Postdose11 Hours Postdose24 Hours Postdose
Pevonedistat 25 mg/m^21.3103.1800.8401.7542.5670.598-2.998-2.478-2.930
Pevonedistat 50 mg/m^2-2.231-0.639-2.127-1.184-1.127-3.465-6.898-8.638-7.653

[back to top]

Part B: Overall Response Rate (ORR)

Percentage of participants who achieve an overall response per investigator's assessment at end of treatment,according to Response Evaluation Criteria in Solid Tumor(RECIST),version 1.1 guideline. Complete response(CR):Disappearance of all target lesions.Any pathological lymph nodes(whether target and non target)must have reduction in short axis to <10 millimeter(mm).Partial Response(PR):atleast 30% decrease in sum of diameter of target lesions,taking as reference baseline sum of diameter.Stable Disease(SD):Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression(PD),taking as reference smallest sum of diameter; PD:atleast 20% increase in sum of diameter of target lesions,taking as reference,smallest sum on study(this includes baseline sum if that is smallest on study).In addition to relative increase of 20%,sum must also demonstrate an absolute increase of atleast 5 mm.Appearance of 1 or more new lesions is also considered progression. (NCT03330106)
Timeframe: Up to Cycle 45 (end of treatment) (Cycle length=21 days)

Interventionpercentage of participants (Number)
Part B: Pevonedistat 25 mg/m^2 + Docetaxel9.1
Part B: Pevonedistat 20 mg/m^2 + Carboplatin + Paclitaxel8.3

[back to top]

Part A: Terminal Phase Elimination Half-life (t1/2) for Pevonedistat

(NCT03330106)
Timeframe: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A

Interventionhours (h) (Mean)
Pevonedistat 25 mg/m^27.21
Pevonedistat 50 mg/m^26.73

[back to top]

Part A: AUC(0-24): Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours Postdose for Pevonedistat

(NCT03330106)
Timeframe: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A

Interventionhour*nanogram per milliliter (h*ng/mL) (Geometric Mean)
Pevonedistat 25 mg/m^21190
Pevonedistat 50 mg/m^22510

[back to top]

Part A: Cmax: Maximum Observed Plasma Concentration for Pevonedistat

(NCT03330106)
Timeframe: Days 1 or 8 predose and at multiple time points (up to 24 hours) post dose in Part A

Interventionnanograms per milliliter (ng/mL) (Geometric Mean)
Pevonedistat 25 mg/m^2197
Pevonedistat 50 mg/m^2509

[back to top]

Objective Response Rate (ORR) of Pembrolizumab + Epacadostat, Pembrolizumab Monotherapy and the EXTREME Regimen

"ORR was defined as the percentage of participants who had a complete response (CR), disappearance of all target lesions or partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions per RECIST v1.1 by investigator determination.~Responses are based on investigator assessments per RECIST 1.1 without confirmation using all available scans." (NCT03358472)
Timeframe: Minimum Week 9

Interventionpercentage of participants (Number)
Pembrolizumab + Epacadostat31.4
Pembrolizumab21.1
EXTREME34.3

[back to top]

Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Experiencing Adverse Events (AEs)

"AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.~Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months." (NCT03358472)
Timeframe: Up to 14 months

InterventionParticipants (Count of Participants)
Pembrolizumab + Epacadostat34
Pembrolizumab17
EXTREME34

[back to top]

Safety and Tolerability of Pembrolizumab + Epacadostat Versus Pembrolizumab Versus the EXTREME Regimen as Measured by Number of Participants Discontinuing Study Treatment Due to AEs

"AE is defined as any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment.~Data reported from start of study to data cutoff 17 Jan 2019, up to 14 months." (NCT03358472)
Timeframe: Up to 14 months

InterventionParticipants (Count of Participants)
Pembrolizumab + Epacadostat3
Pembrolizumab2
EXTREME7

[back to top]

Overall Survival (OS)

OS is defined as the time from maintenance randomization until death of any cause. (NCT03382561)
Timeframe: Every 6 weeks for 6 months, then every 8 weeks until 1 year, and then every 12 weeks until off treatment or end of observation. Then every 3 months if < 2 years from registration, every 6 months for years 2-3, and yearly up to 3 years 9 months.

Interventionmonths (Median)
Arm A (Cisplatin/Carboplatin, Etoposide and Nivolumab; CEN)11.2
Arm B (Cisplatin/Carboplatin and Etoposide; CE)8.1

[back to top]

Progression-free Survival (PFS)

"PFS is defined as the time from randomization to documented disease progression or death from any cause, whichever occurs first. Patients who have not experienced an event of interest by the time of analysis will be censored at the date they are last known to be alive and progression-free.~Progression was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Progression was defined as appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions, or at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm." (NCT03382561)
Timeframe: Every 6 weeks for 6 months, then every 8 weeks until 1 year, and then every 12 weeks until being off treatment or end of observation. Thereafter every 3 months if < 2 years from registration, every 6 months for years 2-3, and yearly up to 3 years 9 months

Interventionmonths (Median)
Arm A (Cisplatin/Carboplatin, Etoposide and Nivolumab; CEN)5.5
Arm B (Cisplatin/Carboplatin and Etoposide; CE)4.9

[back to top]

Response Rate

"Best overall response was evaluated using the revised Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1). Response was defined as complete response (CR) or partial response (PR).~CR: Disappearance of all lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm.~PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters." (NCT03382561)
Timeframe: Every 6 weeks for 6 months, then every 8 weeks until 1 year, and then every 12 weeks until being off treatment or end of observation. Thereafter every 3 months if < 2 years from registration, every 6 months for years 2-3, and yearly up to 3 years 9 months

Interventionproportion of participants (Number)
Arm A (Cisplatin/Carboplatin, Etoposide and Nivolumab; CEN)0.77
Arm B (Cisplatin/Carboplatin and Etoposide; CE)0.80

[back to top]

Number of Participants With Pathologic Complete Remission

Cytoreduction pathologic complete remission will be measured using RECIST (Response Evaluation Criteria in Solid Tumors) and immune-related response criteria. (NCT03394885)
Timeframe: 9 weeks

InterventionParticipants (Count of Participants)
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)0

[back to top]

Safety: Incidence of Post Chemotherapy Surgical Debulking

The number of subjects able to undergo interval cytoreductive surgery will be utilized as a measure of safety regarding the initial dosing of atezolizumab. (NCT03394885)
Timeframe: 9 weeks

InterventionParticipants (Count of Participants)
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)15

[back to top]

Safety: Dose Intensity

Percentage of planned doses of atezolizumab received at each cycle (21 day period) will be utilized as a measure of safety and tolerability for each subject. (NCT03394885)
Timeframe: Cycles 1-6,18 months total

Interventionpercentage of planned doses (Number)
Cycle 1Cycle 2Cycle 3Cycle 4Cycle 5Cycle 6
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)100.081.393.386.786.7100.0

[back to top]

Safety: Incidence of Dose Modifications

The number of dose modifications for atezolizumab at each cycle (21 day period) will be utilized as a measure of safety and tolerability for each subject. Dose modifications are defined as doses delayed, doses discontinued, or doses held. (NCT03394885)
Timeframe: Cycles 1-6,18 months total

Interventiondose modifications (Number)
Cycle 1Cycle 2Cycle 3Cycle 4Cycle 5Cycle 6
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)031232

[back to top]

Translational: Fold Change in Cytokine Expression

Analyzing changes in cytokine expression based on: ELISA (enzyme-linked immunosorbent assay) after treatment with atezolizumab, association with BRCA mutation status, tumor mutation profile (next generation sequencing) and progression free survival. (NCT03394885)
Timeframe: Baseline, 18 months

InterventionFold change (Median)
CXCL10 Fold ChangeINFgamma Fold ChangeIL10 Fold ChangeIL12p70 Fold ChangeIL1b Fold ChangeIL2RA Fold ChangeIL6 Fold ChangeTNFalpha Fold ChangeTIM3 Fold Change
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)0.70.80.91.40.91.10.40.81.0

[back to top]

Progression Free Survival Rate

All patients will be evaluated for progression free survival from the date of first treatment to the date of first observation of progressive disease or death due to any cause or will be stopped at date of last follow-up for those still alive without disease progression. 18-month progression free survival rate as estimated by Kaplan-Meier method. (NCT03394885)
Timeframe: 18 months

Interventionproportion of participants (Number)
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)0.65

[back to top]

Overall Survival Rate

All patients will be evaluated for overall survival from the date of first treatment on protocol to the date of death due to any cause and will be stopped at date of last follow-up for those still alive.18-month overall survival rate as estimated by Kaplan-Meier method. (NCT03394885)
Timeframe: 18 months

Interventionproportion of participants (Number)
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)0.93

[back to top]

Number of Participants With a Complete or Partial Response as Measured by RECIST (Response Evaluation Criteria in Solid Tumors)

RECIST criteria will be utilized for subjects over the course of the study to measure their response to study drugs. A Complete Response (disappearance of all tumor lesions) or Partial Response (reduction of greater than 30% in total tumor size) is considered a response. (NCT03394885)
Timeframe: 18 months

InterventionParticipants (Count of Participants)
Atezolizumab, Carboplatin, Paclitaxel (+Optional Bevacizumab)12

[back to top]

Objective Response Rate by RECIST 1.1 Among BRCA-mutant Patients

"ORR defined as the proportion of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., non-CR/non-PD in non-target lesions]; and no new lesions) based on RECIST 1.1.~BRCA-mutant patients were those with BRCA1 or BRCA2 mutations." (NCT03414684)
Timeframe: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

Interventionpercent of patients (Number)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion50.0

[back to top]

Second-course Time to Objective Response Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab

TTOR defined as the time from start of crossover treatment to the date of the first documented CR or PR by RECIST 1.1 on second-course therapy, whichever is first recorded (NCT03414684)
Timeframe: Assessed from the start of crossover therapy to the time of first response on crossover therapy, up to 2.8 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician DiscretionNA

[back to top]

Objective Response Rate by RECIST 1.1 Among PD-L1-positive Patients

"ORR defined as the proportion of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., non-CR/non-PD in non-target lesions]; and no new lesions) based on RECIST 1.1.~PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1." (NCT03414684)
Timeframe: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

Interventionpercent of patients (Number)
Arm A: Carboplatin + Nivolumab23.1
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion27.3

[back to top]

Objective Response Rate by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1

"Defined as the percentage of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., non-CR/non-PD in non-target lesions]; and no new lesions) based on RECIST 1.1" (NCT03414684)
Timeframe: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

Interventionpercent of patients (Number)
Arm A: Carboplatin + Nivolumab25.0
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion23.3

[back to top]

Second-course Objective Response Rate by irRC Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab

ORR by irRC defined as the proportion of patients achieving an immune-related complete response (complete disappearance of all target and non-target lesions; no new measurable/unmeasurable lesions) or immune-related partial response (a decrease of the immune-related sum of product diameters [irSPD] of 50% or greater) based on irRC, during second-course therapy (NCT03414684)
Timeframe: Assessed from the start of crossover treatment until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 2.8 years

Interventionpercent of patients (Number)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion20.0

[back to top]

Second-course Progression-free Survival Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab

PFS defined as the time from the start of crossover treatment to the earlier of progression (on crossover therapy) or death due to any cause; participants alive without disease progression are censored at date of last disease evaluation. (NCT03414684)
Timeframe: Assessed from the start of crossover therapy to the date of first documented progression on crossover therapy or the date of death from any cause, whichever came first, up to 2.8 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion4.1

[back to top]

Time to Objective Response Among PD-L1-positive Patients

"TTOR defined as the time from randomization to the date of the first documented CR or PR by RECIST 1.1, whichever is first recorded.~PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1." (NCT03414684)
Timeframe: Assessed from randomization to the time of first response, up to 3.5 years

Interventionmonths (Median)
Arm A: Carboplatin + NivolumabNA
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician DiscretionNA

[back to top]

Second-course Overall Survival Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab

Second-course OS defined as the time from the start of crossover treatment to death due from any cause, or censored at date last known alive. (NCT03414684)
Timeframe: Assessed from the start of crossover therapy until the date of death from any cause, up to 2.8 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion12.9

[back to top]

Second-course Objective Response Rate by RECIST 1.1 Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab

"ORR defined as the proportion of patients achieving a complete response (complete disappearance of all target and non-target lesions; no new lesions) or partial response (at least 30% decrease in the sum of the diameters of target lesions; persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits [i.e., non-CR/non-PD in non-target lesions]; and no new lesions) based on RECIST 1.1., during crossover therapy" (NCT03414684)
Timeframe: Assessed from the start of crossover treatment until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 2.8 years

Interventionpercent of patients (Number)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion20.0

[back to top]

Second-course Duration of Response Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab

DOR defined as the time measurement criteria are met for second-course CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented thereafter. Patients without events reported are censored at the last disease evaluation. (NCT03414684)
Timeframe: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) on crossover therapy to the time of first progression on crossover therapy, up to 2.5 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion1.81

[back to top]

Duration of Response

Defined as the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Patients without events reported are censored at the last disease evaluation. (NCT03414684)
Timeframe: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) to the time of first progression, up to 2.75 years

Interventionmonths (Median)
Arm A: Carboplatin + Nivolumab19.3
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion7.7

[back to top]

Clinical Benefit Rate Among PD-L1-positive Patients

"CBR defined as the proportion of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks.~PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1." (NCT03414684)
Timeframe: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

Interventionpercent of patients (Number)
Arm A: Carboplatin + Nivolumab30.8
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion36.4

[back to top]

Clinical Benefit Rate Among BRCA-mutant Patients

"CBR defined as the percentage of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks.~BRCA-mutant patients were those with BRCA1 or BRCA2 mutations." (NCT03414684)
Timeframe: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

Interventionpercent of patients (Number)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion50.0

[back to top]

Clinical Benefit Rate

Defined as the proportion of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks (NCT03414684)
Timeframe: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

Interventionpercent of patients (Number)
Arm A: Carboplatin + Nivolumab34.4
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion33.3

[back to top]

Overall Survival

Defined as the time from randomization to death due to any cause, or censored at date last known alive (NCT03414684)
Timeframe: Assessed from date of randomization until the date of death from any cause, up to 3.5 years

Interventionmonths (Median)
Arm A: Carboplatin + Nivolumab16.8
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion11.1

[back to top]

Overall Survival Among BRCA-mutant Patients

"OS defined as the time from randomization to death due to any cause, or censored at date last known alive.~BRCA-mutant patients were those with BRCA1 or BRCA2 mutations." (NCT03414684)
Timeframe: From date of randomization until the date of death from any cause, assessed up to 3.5 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion24.4

[back to top]

Second-course Clinical Benefit Rate Among Patients Who Crossed Over to Nab-paclitaxel Plus Nivolumab

CBR defined as the proportion of patients achieving a complete response or partial response by RECIST 1.1, or stable disease lasting greater than or equal to 24 weeks, during second course therapy (NCT03414684)
Timeframe: Assessed from the start of crossover treatment until disease progression, intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 2.8 years

Interventionpercent of patients (Number)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion30.0

[back to top]

Overall Survival Among PD-L1-positive Patients

"OS defined as the time from randomization to death due to any cause, or censored at date last known alive.~PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1." (NCT03414684)
Timeframe: Assessed from date of randomization until the date of death from any cause, up to 3.5 years

Interventionmonths (Median)
Arm A: Carboplatin + Nivolumab17.6
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion10.7

[back to top]

Progression-free Survival

Defined as the time from randomization to the earlier of progression or death due to any cause. Participants alive without disease progression are censored at date of last disease evaluation (NCT03414684)
Timeframe: Assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3.5 years

Interventionmonths (Median)
Arm A: Carboplatin + Nivolumab4.2
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion5.5

[back to top]

Progression-free Survival Among PD-L1-positive Patients

"PFS defined as the time from randomization to the earlier of progression or death due to any cause; participants alive without disease progression are censored at date of last disease evaluation.~PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1." (NCT03414684)
Timeframe: Assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3.5 years

Interventionmonths (Median)
Arm A: Carboplatin + Nivolumab8.3
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion4.7

[back to top]

Progression-free Survival Among BRCA-mutant Patients

"PFS defined as the time from randomization to the earlier of progression or death due to any cause; participants alive without disease progression are censored at date of last disease evaluation.~BRCA-mutant patients were those having BRCA1 or BRCA2 mutations." (NCT03414684)
Timeframe: Assessed from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, up to 3.5 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion4.74

[back to top]

Time to Objective Response Among BRCA-mutant Patients

"TTOR defined as the time from randomization to the date of the first documented CR or PR by RECIST 1.1, whichever is first recorded.~BRCA-mutant patients were those with BRCA1 or BRCA2 mutations." (NCT03414684)
Timeframe: Assessed from randomization to the time of first response, up to 3.5 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion3.2

[back to top]

Time to Objective Response

Defined as the time from randomization to the date of the first documented CR or PR by RECIST 1.1, whichever is first recorded (NCT03414684)
Timeframe: Assessed from randomization to the time of first response, up to 3.5 years

Interventionmonths (Median)
Arm A: Carboplatin + Nivolumab4.6
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion11.2

[back to top]

Objective Response Rate by irRC Among PD-L1-positive Patients

"ORR by irRC defined as the proportion of patients achieving an immune-related complete response (complete disappearance of all target and non-target lesions; no new measurable/unmeasurable lesions) or immune-related partial response (a decrease of the immune-related sum of product diameters [irSPD] of 50% or greater) based on irRC.~PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1." (NCT03414684)
Timeframe: Assessed from the start of treatment until disease progression, complete response (after at least 24 weeks of treatment), intercurrent illness, unacceptable toxicity, noncompliance/withdrawal, or general/specific worsening of condition, up to 3.5 years

Interventionpercent of patients (Number)
Arm A: Carboplatin + Nivolumab30.8

[back to top] [back to top]

Duration of Response Among PD-L1-positive Patients

"DOR defined as the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Patients without events reported are censored at the last disease evaluation.~PD-L1 positivity defined as ≥1% of the tumor cell population demonstrating unequivocal staining for PD-L1." (NCT03414684)
Timeframe: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) to the time of first progression, up to 2.75 years

Interventionmonths (Median)
Arm A: Carboplatin + Nivolumab16.8
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion4.9

[back to top]

Duration of Response Among BRCA-mutant Patients

"DOR defined as the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented. Patients without events reported are censored at the last disease evaluation.~BRCA-mutant patients were those with BRCA1 or BRCA2 mutations." (NCT03414684)
Timeframe: Assessed from the time measurement criteria are met for CR or PR by RECIST 1.1 (whichever is first recorded) to the time of first progression, up to 3.5 years

Interventionmonths (Median)
Arm B: Carboplatin, Then Nivolumab +/- Nab-paclitaxel After Progression, Per Physician Discretion2.04

[back to top]

Phase 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator Assessment

ORR is defined as the percentage of participants who achieved confirmed complete response (CR) or confirmed partial response (PR), according to response evaluation criteria in solid tumors (RECIST) version1.1. As per RECIST version 1.1, CR: disappearance of all lesions; all lymph nodes were non-pathological in size and normalization of tumor marker level; PR: greater than or equal to (>=) 30 percent (%) decrease in the sum of the diameters of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of nontarget lesions. (NCT03473743)
Timeframe: From Day 1 up to 36 months

InterventionPercentage of Participants (Number)
Arm A (Phase 2): Erdafitinib 8/9 mg Monotherapy44.2
Arm B (Phase 2): Erdafitinib 8 mg + Cetrelimab 240/480 mg54.5

[back to top]

Phase 2: Number of Participants With Treatment-emergent Adverse Event (TEAEs)

Number of participants with TEAEs were reported. An adverse event is any untoward medical event that occurs in a participant administered an investigational product and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs were defined as adverse events with onset or worsening on or after date of first dose of study treatment. (NCT03473743)
Timeframe: From Day 1 up to 36 months

InterventionParticipants (Count of Participants)
Arm A (Phase 2): Erdafitinib 8/9 mg Monotherapy43
Arm B (Phase 2): Erdafitinib 8 mg + Cetrelimab 240/480 mg44

[back to top]

Phase 1b: Number of Participants With Dose-Limiting Toxicity (DLTs)

Number of participants with DLTs were reported. The DLTs as per National Cancer Institute Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE version 5.0) are specific adverse events defined as grade 3 (severe), grade 4 (life-threatening), and grade 5 (death) non-hematological toxicity or hematological toxicity. (NCT03473743)
Timeframe: Up to 8 weeks

InterventionParticipants (Count of Participants)
Cohort Dose Level (DL) 1 (Phase 1b): Erdafitinib 6 Milligrams (mg) + Cetrelimab 240/480 mg0
Cohort DL2A (Phase 1b): Erdafitinib 8 mg + Cetrelimab 240/480 mg0
Cohort DL2B (Phase 1b): Erdafitinib 8/9 mg + Cetrelimab 240/480 mg0
Cohort DL2 (Phase 1b): Erdafitinib 8/9 mg + Cetrelimab 240/480 mg (RP2D)0
Cohort DL2C (Phase 1b): Erdafitinib 8 mg + Cetrelimab 360 mg + Cisplatin 50 mg/m^20
Cohort DL2D (Phase 1b): Erdafitinib 8 mg + Cetrelimab 360 mg + Carboplatin AUC 4 mg/mL/Min0

[back to top]

Overall Survival

Time is calculated from the diagnosis to the date of the last follow-up date if no death event, or the date of death. (NCT03480750)
Timeframe: 36 months

Interventionmonths (Median)
Trientine With Chemotherapy14.4

[back to top]

Maximum Plasma Concentration [Cmax] of Trientine

Trientine (TETA) prior to and within 24 hrs and 7 days after trientine (NCT03480750)
Timeframe: 0, 10mins, 30mins, 60mins, 90mins, 120mins, 4h, 6h, 24h, 148h, 150h, 153h, 156h post 1st dose of trientine

Interventionmg/L (Median)
Trientine With Chemotherapy Dose Level 1 (300mg)1.87
Trientine With Chemotherapy Dose Level 2 (600mg)5.07
Trientine With Chemotherapy Dose Level 3 (900mg)11.54
Trientine With Chemotherapy Dose Level 4 (1200mg)14.98
Trientine With Chemotherapy Dose Level 5 (1500mg)13.08
Trientine With Chemotherapy Dose Level 6 (1800mg)29.35

[back to top]

Maximum Tolerated Dose, MTD

'3+3' study design. MTD will be defined at the dose level of trientine prior to the level with DLT events ≧ 2/6 participants. (NCT03480750)
Timeframe: within 36 days after the start of Trientine

Interventionmg (Number)
Trientine With Chemotherapy Dose Level 1 - 6 (300 -1800mg)NA

[back to top]

Number of Participants With Dose-Limiting Toxicity (DLT)

(1) Grade 4 neutropenia (ANC <500/cumm^3) or thrombocytopenia ≧7 days; (2) Hematologic toxicities ≧ Grade 3, eg. febrile neutropenia <1,000/cumm^3, or platelet count <25,000/cumm^3 with hemorrhage ≧ 7 days; (3) Non-hematologic toxicities ≧ grade 3, eg. ALT or AST, ≧ 7days; other non-hematologic toxicities ≧ grade 3 (except alopecia, non-chemotherapy related nausea/vomiting); (4) Neurologic toxicities ≧ grade 2, eg. dizziness, or lethargy ≧ 3 days (NCT03480750)
Timeframe: 36 days

InterventionParticipants (Count of Participants)
Trientine With Chemotherapy at Dose Level 1 (300mg/d)0
Trientine With Chemotherapy at Dose Level 2 (600mg/d)0
Trientine With Chemotherapy at Dose Level 3 (900mg/d)0
Trientine With Chemotherapy at Dose Level 4 (1200mg/d)0
Trientine With Chemotherapy Dose Level 5 (1500mg/d)0
Trientine With Chemotherapy Dose Level 6 (1800mg/d)0

[back to top]

Percentage of Participants With Measurable Tumor Treatment Response Assessed by RECIST Criteria 1.1

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT scan (NCT03480750)
Timeframe: 176 days

Interventionpercentage of participants (Number)
Clinical benefit ratesResponse rates
Trientine With Chemotherapy43.825.0

[back to top]

Progression-free Survival

Time is calculated from the diagnosis to the last follow-up date if no disease progression , or the date of disease progression after the last treatment cycle of the study drugs (NCT03480750)
Timeframe: 36 months

Interventionmonths (Median)
Trientine With Chemotherapy4.6

[back to top]

Part A: Terminal Disposition Phase Half-life (T1/2z) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

(NCT03486314)
Timeframe: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Interventionhour (Mean)
Pevonedistat without rifampin (Day 1)Pevonedistat with rifampin (Day 10)
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg7.4425.708

[back to top]

Part A: Ratio of Maximum Observed Plasma Concentration (Cmax) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

The Least square (LS) means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model. (NCT03486314)
Timeframe: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Interventionratio (Least Squares Mean)
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg0.962

[back to top]

Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model. (NCT03486314)
Timeframe: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Interventionratio (Least Squares Mean)
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg0.785

[back to top]

Part A: Ratio of Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC∞) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

The LS means ratio of Day 10 over Day 1 were calculated from a mixed-model analysis of variance model. (NCT03486314)
Timeframe: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Interventionratio (Least Squares Mean)
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg0.790

[back to top]

Part B: Number of Participants With Best Overall Response as Per Investigator's Assessment

Best overall response was defined as participants with best response among complete response (CR) or partial response (PR) or stable disease (SD), or progressive disease (PD). It was assessed by investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target and non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR: at least 30 percent (%) decrease in sum of diameter of target lesions, taking as reference baseline sum of diameter. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference smallest sum of diameter. PD: at least 20% increase in sum of diameter of target lesions, taking as reference, smallest sum on study. (NCT03486314)
Timeframe: Up to Cycle 17 (end of treatment) (Cycle length =21 days)

,
InterventionParticipants (Count of Participants)
CRPRSDPD
Part B: Pevonedistat 20 mg/m^2 + Carboplatin AUC5 + Paclitaxel 175 mg/m^20133
Part B: Pevonedistat 25 mg/m^2 + Docetaxel 75 mg/m^20222

[back to top]

Part A: Volume of Distribution at Steady State After Intravenous Administration (Vss) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

(NCT03486314)
Timeframe: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Interventionliter (Mean)
Pevonedistat without rifampin (Day 1)Pevonedistat with rifampin (Day 10)
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg312.82296.10

[back to top]

Part A: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10)

(NCT03486314)
Timeframe: Days 1 and 10 pre-dose and at multiple time points (up to 48 hours) post-dose

Interventionliter per hour (L/h) (Mean)
Pevonedistat without rifampin (Day 1)Pevonedistat with rifampin (Day 10)
Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg35.2243.77

[back to top]

All Collected Deaths

"On-treatment deaths were collected from first dose of study medication to 30 days after the last dose of study medication for a maximum duration of 2.9 years.~Extended safety follow up deaths were collected from day 31 post treatment up to 150 days post-treatment, for a maximum duration of 3.2 years.~Post-treatment deaths were collected after 150 days post-treatment, for a maximum duration of 3.2 years." (NCT03499899)
Timeframe: Up to 2.9 years (on-treatment), up to 3.2 years (extended safety follow-up and post-treatment)

,,
InterventionParticipants (Count of Participants)
On-treatmentExtended safety follow-up deathsPost-treatment deathsAll deaths
LAG525 + Carboplatin1161128
LAG525 + PDR00107815
LAG525+ PDR001+ Carboplatin271524

[back to top]

Time to Response (TTR) Per Investigator's Assessment According to RECIST v1.1

"TTR is the time from date of randomization to first documented response of CR or PR based on investigators' assessment and according to RECIST 1.1. Median TTR was summarized using descriptive statistics.~CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters." (NCT03499899)
Timeframe: From date of randomization to first documented response (CR or PR), up to approximately 14 months

InterventionMonths (Median)
LAG525 + PDR0011.5
LAG525+ PDR001+ Carboplatin1.7
LAG525 + Carboplatin1.4

[back to top]

Progression Free Survival (PFS)

PFS is defined as time from date of randomization to the date of first documented progression or death due to any cause. PFS was assessed via investigator's assessment according to RECIST 1.1. PFS was censored at the date of the last adequate tumor assessment if no PFS event was observed prior to the analysis cut-off date or before the start of the new anticancer therapy date, whichever is earlier. The PFS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley. (NCT03499899)
Timeframe: From date of randomization to disease progression or death due to any cause, whichever occurs first, up to approximately 14 months

InterventionMonths (Median)
LAG525 + PDR0011.4
LAG525+ PDR001+ Carboplatin4.3
LAG525 + Carboplatin3.0

[back to top]

PK Parameter, Cmax of Carboplatin (Ultrafilterable Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as ultrafilterable platinum) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionng/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin2570014700
LAG525+ PDR001+ Carboplatin2320022300

[back to top]

PK Parameter, Cmax of Carboplatin (Total Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed carboplatin plasma concentration (determined as total platinum) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionng/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin2140020000
LAG525+ PDR001+ Carboplatin2230020900

[back to top]

Duration of Response (DOR) Per Investigator's Assessment According to RECIST v1.1

"DOR is the time between the first documented response (CR or PR) and the first documented progression or death due to underlying cancer based on RECIST1.1 and as per investigator's assessment. The DOR distribution was estimated using the Kaplan-Meier method and the 95% confidence intervals using the method of Brookmeyer and Crowley. If progression or death did not occur, the participant was censored at the date of last adequate tumor assessment.~CR: Disappearance of all non-nodal target lesions and any pathological lymph nodes assigned as target lesions must have a reduction in short axis to <10 mm.~PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.~Progression: at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. The sum must also demonstrate an absolute increase of at least 5 mm." (NCT03499899)
Timeframe: From first documented response up to disease progression or death due to underlying cancer, whichever occurs first, up to approximately 14 months

InterventionMonths (Median)
LAG525 + PDR0014.9
LAG525+ PDR001+ Carboplatin13.6
LAG525 + Carboplatin12.6

[back to top]

PK Parameter, AUClast of PDR001

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of PDR001 (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,
Interventionday*ug/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + PDR001780374
LAG525+ PDR001+ Carboplatin8901500

[back to top]

Overall Response Rate (ORR) Per Investigator's Assessment According to RECIST v1.1

"Overall response rate (ORR) is defined as the percentage of participants with best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1 based on investigator's assessment. The 95% CIs were computed using two-sided exact binomial method.~CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters." (NCT03499899)
Timeframe: Up to approximately 14 months

InterventionPercentage of participants (Number)
LAG525 + PDR0015.0
LAG525+ PDR001+ Carboplatin32.4
LAG525 + Carboplatin17.6

[back to top]

Overall Survival (OS)

OS is defined as the time from date of randomization to date of death due to any cause. If a participant was not known to have died, then OS was censored at the latest date the participant was known to be alive (on or before the cut-off date). The OS distribution was estimated using the Kaplan-Meier method. The 95% confidence intervals were calculated using the method of Brookmeyer and Crowley (NCT03499899)
Timeframe: From date of randomization to date of death due to any cause, up to 18 months

InterventionMonths (Median)
LAG525 + PDR0016.1
LAG525+ PDR001+ Carboplatin11.6
LAG525 + Carboplatin8.0

[back to top]

PK Parameter, Cmax of LAG525

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed plasma LAG525 concentration (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,,
Interventionug/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin128168
LAG525 + PDR001127144
LAG525+ PDR001+ Carboplatin136181

[back to top]

PK Parameter, Cmax of PDR001

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Cmax is the maximum observed PDR001 serum concentration (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,
Interventionug/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + PDR00178.095.1
LAG525+ PDR001+ Carboplatin82.4117

[back to top]

PK Parameter, Tmax of Carboplatin (Total Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as total platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionhr (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin0.7200.720
LAG525+ PDR001+ Carboplatin0.8570.789

[back to top]

PK Parameter, Tmax of Carboplatin (Ultrafilterable Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum carboplatin plasma concentration (determined as ultrafilterable platinum). Actual time of sample collection was used (not the nominal time point as per scheduled assessment) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionhr (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin0.6600.686
LAG525+ PDR001+ Carboplatin0.8020.828

[back to top]

PK Parameter, AUClast of LAG525

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of LAG525 (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,,
Interventionday*ug/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin10101490
LAG525 + PDR0011170240
LAG525+ PDR001+ Carboplatin13102040

[back to top]

PK Parameter, Tmax of PDR001

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum PDR001 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,
Interventionhr (Geometric Mean)
Cycle 1Cycle 3
LAG525 + PDR0011.431.67
LAG525+ PDR001+ Carboplatin1.711.61

[back to top]

Clinical Benefit Rate (CBR) Per Investigator's Assessment According to RECIST v1.1

"CBR is defined as the percentage of participants with a best overall response (BOR) of confirmed CR or PR, or stable disease (SD) lasting 24 weeks or longer, according to RECIST 1.1 criteria. The 95% CI were computed using two-sided exact binomial method.~CR: Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.~SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease." (NCT03499899)
Timeframe: Up to approximately 14 months

InterventionPercentage of Participants (Number)
LAG525 + PDR0015.0
LAG525+ PDR001+ Carboplatin35.3
LAG525 + Carboplatin20.6

[back to top]

PK Parameter, Tmax of LAG525

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. Tmax is the time to reach maximum LAG525 serum concentration. Actual time of sample collection was used (not the nominal time point as per scheduled assessment) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,,
Interventionhr (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin1.581.77
LAG525 + PDR0011.511.64
LAG525+ PDR001+ Carboplatin1.761.58

[back to top]

PK Parameter, AUClast of Carboplatin (Ultrafilterable Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as ultrafilterable platinum) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionng/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin3560036300
LAG525+ PDR001+ Carboplatin4140037400

[back to top]

PK Parameter, AUClast of Carboplatin (Total Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUClast is the area under the curve (AUC) from time zero to the last measurable concentration sampling time (tlast) of carboplatin (determined as total platinum) (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionng/mL (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin3890042600
LAG525+ PDR001+ Carboplatin4200040800

[back to top]

PK Parameter, AUC0-4h of Carboplatin (Total Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as total platinum). (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionhour*nanogram/miliLiter (hr*ng/mL) (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin4520043500
LAG525+ PDR001+ Carboplatin4500042700

[back to top]

PK Parameter, AUC0-504h of PDR001

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-504h was defined as the area under the plasma concentration-time curve from time zero to 504h. (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,
Interventionday*ug/mL (Mean)
Cycle 1Cycle 3
LAG525 + PDR0018191490
LAG525+ PDR001+ Carboplatin9071710

[back to top]

PK Parameter, AUC0-4h of Carboplatin (Ultrafilterable Platinum)

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-4h was defined as the area under the plasma concentration-time curve from time zero to 4h (determined as ultrafilterable platinum). (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Cycle 3 at pre-infusion, end of infusion, 1 hour, 2 hours and 3 hours post end of infusion. Each cycle is 21 days

,
Interventionhour*nanogram/miliLiter (hr*ng/mL) (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin4470041000
LAG525+ PDR001+ Carboplatin4360041100

[back to top]

Pharmacokinetics (PK) Parameter, Area Under the Plasma Concentration Versus Time Curve From Time 0 to 504 Hours (AUC0-504h) of LAG525

Blood samples were collected at the indicated time points for PK analysis. PK parameters were calculated by standard non-compartmental analysis. AUC0-504h was defined as the area under the plasma concentration-time curve from time zero to 504h. (NCT03499899)
Timeframe: Cycle 1 at pre-infusion, 1 hour (hr) post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 1. Cycle 3 at pre-infusion, 1 hr post end of infusion, 168 hr, 336 hr and 504 hr post-infusion on Day 1 of Cycle 3. Each cycle is 21 days

,,
Interventionday*microgram/miliLiter (day*ug/mL) (Geometric Mean)
Cycle 1Cycle 3
LAG525 + Carboplatin11801990
LAG525 + PDR00112702060
LAG525+ PDR001+ Carboplatin13502200

[back to top]

Number of Participants With Anti-drug Antibodies (ADA) on Treatment for PDR001

Number of participants who were treatment-induced ADA positive for PDR001 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for PDR001 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer) (NCT03499899)
Timeframe: From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 2.8 years

InterventionParticipants (Count of Participants)
LAG525 + PDR0011
LAG525+ PDR001+ Carboplatin0

[back to top]

Number of Participants With Anti-drug Antibodies (ADA) on Treatment for LAG525

Number of participants who were treatment-induced ADA positive for LAG525 (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive for LAG525 (post-baseline ADA positive with titer that was at least the fold titer change greater than the ADA-positive baseline titer) (NCT03499899)
Timeframe: From Cycle 1 to Cycle 7 (Day 1 pre-infusion) and end of treatment, assessed up to 3 years

InterventionParticipants (Count of Participants)
LAG525 + PDR0010
LAG525+ PDR001+ Carboplatin0
LAG525 + Carboplatin1

[back to top]

Number of Participants With Anti-drug Antibodies (ADA) at Baseline for PDR001

Number of participants who had an ADA positive result at baseline for PDR001. (NCT03499899)
Timeframe: Baseline

InterventionParticipants (Count of Participants)
LAG525 + PDR0013
LAG525+ PDR001+ Carboplatin6

[back to top]

Number of Participants With Anti-drug Antibodies (ADA) at Baseline for LAG525

Number of participants who had an ADA positive result at baseline for LAG525 (NCT03499899)
Timeframe: Baseline

InterventionParticipants (Count of Participants)
LAG525 + PDR0010
LAG525+ PDR001+ Carboplatin0
LAG525 + Carboplatin1

[back to top]

Progression-free Survival (PFS) by Independent Review Committee (IRC) Assessment

PFS is defined as the time from randomization until first documentation of progression or death from any cause, whichever occurs first, as assessed by the IRC per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (NCT03594747)
Timeframe: Up to approximately 2 years and 2 months; data presented as of primary analysis data cut off date of 30SEP2020

InterventionMonths (Median)
Tislelizumab + Paclitaxel + Carboplatin7.7
Tislelizumab + Nab-paclitaxel + Carboplatin9.6
Paclitaxel + Carboplatin5.5

[back to top]

OS (Overall Survival)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were to be censored at the date of the last follow-up. OS was reported for each arm. (NCT03629925)
Timeframe: Through Database Cutoff Date of 15 October 2019 (up to approximately 13 months)

InterventionMonths (Median)
Sintilimab+ Gemcitabine Plus PlatinumNA
Placebo+Gemcitabine Plus PlatinumNA

[back to top]

DCR (Disease Control Rate)

DCR was defined as the percentage of participants who had a CR (disappearance of all target lesions), PR (at least a 30% decrease in the sum of diameters of target lesions), or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD]). The percentage of participants who experienced a confirmed CR, PR, or SD according to RECIST 1.1 as assessed by BIRRC was reported as the DCR for each arm. (NCT03629925)
Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

InterventionPercentage of Participants (Number)
Sintilimab+ Gemcitabine Plus Platinum86.0
Placebo+Gemcitabine Plus Platinum80.3

[back to top]

DOR (Duration of Response)

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until progressive disease (PD) or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD. DOR assessments were based on BIRRC assessment. The DOR according to RECIST 1.1 for all participants who experienced a confirmed CR or PR was reported for each arm. (NCT03629925)
Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

InterventionMonths (Median)
Sintilimab+ Gemcitabine Plus Platinum6.05
Placebo+Gemcitabine Plus Platinum5.06

[back to top]

ORR(Objective Response Rate)

ORR was defined as the percentage of participants in the analysis population who had a confirmed Complete Response (CR: disappearance of all lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The percentage of participants who experienced a confirmed CR or PR according to RECIST 1.1 as assessed by BIRRC was reported as the ORR for each arm. (NCT03629925)
Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

InterventionPercentage of Participants (Number)
Sintilimab+ Gemcitabine Plus Platinum44.7
Placebo+Gemcitabine Plus Platinum35.4

[back to top]

TTR (Time to Response)

TTR was defined as the time of participants from the first treatment administration to the first incidence of a confirmed CR (disappearance of all lesions) or PR (at least a 30% decrease in the sum of diameters [SOD] of target lesions, taking as reference the baseline SOD) according to RECIST 1.1. The time from first treatment administration to the first incidence of treatment response was reported as the TTR for each arm. (NCT03629925)
Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

InterventionMonths (Median)
Sintilimab+ Gemcitabine Plus Platinum1.41
Placebo+Gemcitabine Plus Platinum1.41

[back to top]

PFS(Progression Free Survival)

PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. PFS according to RECIST 1.1 as assessed by BIRRC was reported for each arm. (NCT03629925)
Timeframe: Through Database Cutoff Date of 25 March 2020 (up to approximately 18 months)

Interventionmonths (Median)
Sintilimab+ Gemcitabine Plus Platinum5.5
Placebo+Gemcitabine Plus Platinum4.9

[back to top]

Number of Participants Who Discontinued From Study Treatment Due to an AE

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued treatment due to an AE was assessed. (NCT03631784)
Timeframe: Up to approximately 1 year

InterventionParticipants (Count of Participants)
Pembrolizumab + cCRT + Paclitaxel + Carboplatin48
Pembrolizumab + cCRT + Pemetrexed + Cisplatin26

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants with at least one AE was assessed. (NCT03631784)
Timeframe: Up to approximately 1 1/4 years

InterventionParticipants (Count of Participants)
Pembrolizumab + cCRT + Paclitaxel + Carboplatin108
Pembrolizumab + cCRT + Pemetrexed + Cisplatin101

[back to top]

Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

ORR was defined as the percentage of participants who experienced a complete response (CR; disappearance of all target lesions) or a partial response (PR; at least a 30% decrease in the sum of diameters of target lesions) and was assessed using modified RECIST 1.1 by blinded independent central review (BICR). (NCT03631784)
Timeframe: Up to approximately 3 years

InterventionPercentage of Participants (Number)
Pembrolizumab + cCRT + Paclitaxel + Carboplatin71.4
Pembrolizumab + cCRT + Pemetrexed + Cisplatin75.5

[back to top]

Percentage of Participants Who Developed Grade 3 or Higher Pneumonitis

Pneumonitis included the MedDRA preferred terms for radiation pneumonitis are acute interstitial pneumonitis, autoimmune lung disease, interstitial lung disease, pneumonitis, idiopathic pneumonia syndrome, organizing pneumonia, and immune-mediated pneumonitis. As per common terminology criteria for Adverse Events, version 4.0, pneumonitis was graded as follows: Grade (Gr) 1- asymptomatic, clinical or diagnostic observations only; intervention not indicated; Gr 2- symptomatic, medical intervention indicated, limiting instrumental activities of daily living (ADL); Gr 3- severe symptoms; limiting self-care activities of daily living (ADL), oxygen indicated; Gr 4- life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation); Gr 5- death. (NCT03631784)
Timeframe: Up to approximately 3 years

InterventionPercentage of Participants (Number)
Pembrolizumab + cCRT + Paclitaxel + Carboplatin8.0
Pembrolizumab + cCRT + Pemetrexed + Cisplatin6.9

[back to top]

Duration of Response (DOR)

DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression,as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurred first. DOR was evaluated for participants who had a objective response of CR or PR. (NCT03635489)
Timeframe: From the date of first occurrence of a complete or partial response until disease progression or death from any cause (up to approximately 24 months)

Interventionmonths (Median)
Placebo + Paclitaxel + Carboplatin8.87
Bevacizumab + Paclitaxel + Carboplatin16.10

[back to top]

Percentage of Participants With Adverse Events (AEs)

(NCT03635489)
Timeframe: From randomization up to 90 days after last dose of study treatment or until initiation of new anti-cancer therapy (up to approximately 76 weeks)

Interventionpercentage of participants (Number)
Placebo + Paclitaxel + Carboplatin100
Bevacizumab + Paclitaxel + Carboplatin100

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Role)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 Months
Placebo + Paclitaxel + Carboplatin34.825.045.250.040.048.140.037.542.9

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Social)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 MonthsSurvival Follow Up 18 MonthsSurvival Follow Up 24 Months
Bevacizumab + Paclitaxel + Carboplatin29.228.928.636.033.347.228.67.728.666.7100

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Social)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 Months
Placebo + Paclitaxel + Carboplatin28.327.338.743.828.933.326.737.528.6

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Physical)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 Months
Placebo + Paclitaxel + Carboplatin17.418.245.243.831.144.413.312.514.3

[back to top]

Progression-Free Survival (PFS)

PFS was defined as time from randomization to the first occurrence of disease progression, as assessed by the Investigator using RECIST v1.1, or death from any cause, whichever occurs first. (NCT03635489)
Timeframe: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 24 months)

Interventionmonths (Median)
Placebo + Paclitaxel + Carboplatin12.32
Bevacizumab + Paclitaxel + Carboplatin22.57

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Bloating

A clinically meaningful improvement in patient-reported abdominal pain or bloating was defined as a ≥10-point decrease from the linearly transformed 0-100 point baseline symptom scale score on each of two items from the Abdominal/Gastrointestinal Symptom Scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 Months
Placebo + Paclitaxel + Carboplatin26.136.429.025.033.325.946.725.028.6

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Physical)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 MonthsSurvival Follow Up 18 MonthsSurvival Follow Up 24 Months
Bevacizumab + Paclitaxel + Carboplatin16.718.434.336.031.027.823.823.128.600

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Emotional)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 Months
Placebo + Paclitaxel + Carboplatin8.713.69.718.811.122.26.712.514.3

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Abdominal Pain

A clinically meaningful improvement in patient-reported abdominal pain or bloating was defined as a ≥10-point decrease from the linearly transformed 0-100 point baseline symptom scale score on each of two items from the Abdominal/Gastrointestinal Symptom Scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 MonthsSurvival Follow Up 18 MonthsSurvival Follow Up 24 Months
Bevacizumab + Paclitaxel + Carboplatin31.342.140.048.045.233.338.146.242.966.70

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Abdominal Pain

A clinically meaningful improvement in patient-reported abdominal pain or bloating was defined as a ≥10-point decrease from the linearly transformed 0-100 point baseline symptom scale score on each of two items from the Abdominal/Gastrointestinal Symptom Scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 Months
Placebo + Paclitaxel + Carboplatin37.040.948.437.537.837.033.350.014.3

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Bloating

A clinically meaningful improvement in patient-reported abdominal pain or bloating was defined as a ≥10-point decrease from the linearly transformed 0-100 point baseline symptom scale score on each of two items from the Abdominal/Gastrointestinal Symptom Scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Ovarian Cancer Module (QLQ-OV28). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 MonthsSurvival Follow Up 18 MonthsSurvival Follow Up 24 Months
Bevacizumab + Paclitaxel + Carboplatin33.347.431.440.033.333.319.023.128.666.70

[back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Role)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 MonthsSurvival Follow Up 18 MonthsSurvival Follow Up 24 Months
Bevacizumab + Paclitaxel + Carboplatin31.336.848.640.042.933.342.930.857.133.30

[back to top] [back to top] [back to top]

Percentage of Participants Who Report a Clinically Meaningful Improvement in Patient-Reported Function (Emotional)

A clinically meaningful improvement in patient-reported function and HRQoL was defined as a >10-point increase from the linearly transformed 0-100 point baseline scale score on each of the four functional (physical, role, emotional, social) scales and global health status/HRQoL scale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire - Core 30 (QLQ-C30). (NCT03635489)
Timeframe: From randomization to the end of treatment/discontinuation (up to approximately 70 weeks), and during follow-up period (up to approximately 24 months)

Interventionpercentage of participants (Number)
Cycle 4 Day 1Cycle 7 Day 1Cycle 13 Day 1Cycle 22 Day 1Treatment Completion / Early Termination VisitSurvival Follow Up 3 MonthsSurvival Follow Up 6 MonthsSurvival Follow Up 9 MonthsSurvival Follow Up 12 MonthsSurvival Follow Up 18 MonthsSurvival Follow Up 24 Months
Bevacizumab + Paclitaxel + Carboplatin22.921.125.728.021.427.838.138.528.600

[back to top]

Objective Response Rate (ORR)

ORR was defined as the proportion of participants with complete response (CR) or partial response (PR) as assessed by investigator according to RECIST v.1.1. (NCT03635489)
Timeframe: Randomization up to disease progression or death from any cause, whichever occurs first (up to approximately 24 months)

Interventionpercentage of participants (Number)
Placebo + Paclitaxel + Carboplatin92.9
Bevacizumab + Paclitaxel + Carboplatin95.8

[back to top]

PFS Per RECIST 1.1 as Assessed by Investigator in Participants With PD-L1 CPS ≥10

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥10 is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy10.4
Placebo+Chemotherapy8.1

[back to top]

PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR)

PFS was defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by BICR is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy12.3
Placebo+Chemotherapy8.3

[back to top]

Number of Participants Who Experienced a Serious AE (SAE)

An SAE was defined as any untoward medical occurrence that, at any dose: a.) Resulted in death; b.) Was life-threatening; c.) Required inpatient hospitalization or prolongation of existing hospitalization; d.) Resulted in persistent or significant disability/incapacity; e.) Was a congenital anomaly/birth defect; f.) Other important medical events; h.) Was a new cancer (that is not a condition of the study) or i.) Was associated with an overdose. The number of participants who experienced an SAE is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionNumber of Participants (Number)
Pembrolizumab+Chemotherapy157
Placebo+Chemotherapy132

[back to top]

Duration of Response (DOR) Per RECIST 1.1 as Assessed by Investigator

For participants who demonstrate CR or PR, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. The DOR per RECIST 1.1 as assessed by Investigator is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy18.0
Placebo+Chemotherapy10.4

[back to top]

PFS Per RECIST 1.1 as Assessed by Investigator in All Participants

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy10.4
Placebo+Chemotherapy8.2

[back to top] [back to top]

Number of Participants Who Discontinued Study Treatment Due to an AE

The number of participants who discontinued study treatment due to an AE is presented. (NCT03635567)
Timeframe: Up to approximately 43 months

InterventionNumber of Participants (Number)
Pembrolizumab+Chemotherapy125
Placebo+Chemotherapy91

[back to top]

OS in All Participants

OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy26.4
Placebo+Chemotherapy16.8

[back to top]

OS in Participants With PD-L1 CPS ≥10

OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥10 is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy29.6
Placebo+Chemotherapy17.4

[back to top]

Overall Survival (OS) in Participants With PD-L1 CPS ≥1

OS was defined as the time from randomization to death due to any cause. The OS for all randomized participants with PD-L1 CPS ≥1 is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy28.6
Placebo+Chemotherapy16.5

[back to top]

Number of Participants With a 10-point Change From Baseline in Quality of Life (QoL) Based on the European Organisation for the Research & Treatment of Cancer (EORTC) QoL Questionnaire-30 (QLQ-C30) Combined Global Score

"The EORTC QLQ-C30 is a questionnaire to assess the quality of life of cancer patients. Participant responses to How would you rate your overall health during the past week? (Item 29) and How would you rate your overall quality of life during the past week? (Item 30) are scored on a 7-point scale (1= Very poor to 7=Excellent). Raw scores are standardized with linear transformation so that scores range from 0-100. A higher combined score indicates a better overall health status. Participant post-baseline scores were classified based on change from baseline, Improved: a ≥10-point improvement in score and confirmed by the next visit; Stable: a ≥10-point increase or <10-point change in score OR a <10-point change in score and a ≥10-point increase in score at the next visit; or Deteriorated: a ≥10-point deterioration in score when the criteria for improvement/stability weren't met. Participants who didn't meet Improved, Stable, or Deteriorated criteria reported as Other." (NCT03635567)
Timeframe: Baseline (Cycle 1 Day 1: Predose) and up to approximately 46 months

,
InterventionNumber of Participants (Number)
ImprovedStableDeterioratedOther
Pembrolizumab+Chemotherapy122106429
Placebo+Chemotherapy86139489

[back to top]

Percentage of Participants That Were PFS Event-Free (PFS Rate) at Month 12 Per RECIST 1.1 as Assessed by Investigator

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS Rate was defined as the percentage of participants that were PFS event-free at Month 12. The PFS Rate per RECIST 1.1 as assessed by Investigator at Month 12 is presented. (NCT03635567)
Timeframe: 12 months

InterventionPercentage of Participants (Number)
Pembrolizumab+Chemotherapy44.7
Placebo+Chemotherapy33.1

[back to top]

Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator in Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by Investigator for all randomized participants with PD-L1 CPS ≥1 is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionMonths (Median)
Pembrolizumab+Chemotherapy10.5
Placebo+Chemotherapy8.2

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An AE was any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experienced an AE is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionNumber of participants (Number)
Pembrolizumab+Chemotherapy305
Placebo+Chemotherapy307

[back to top]

Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by Investigator

ORR was defined as the percentage of the participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters). The ORR per RECIST 1.1 as assessed by Investigator is presented. (NCT03635567)
Timeframe: Up to approximately 46 months

InterventionPercentage of Participants (Number)
Pembrolizumab+Chemotherapy66.2
Placebo+Chemotherapy51.5

[back to top]

Overall Survival (OS)

OS is defined as the time from the start of treatment to death due to any cause. The Kaplan-Meier estimate of median PFS using the product-limit (Kaplan-Meier) method for censored data is presented. (NCT03664024)
Timeframe: Up to ~36 months

InterventionMonths (Median)
Pembrolizumab Plus Platinum-doublet Chemotherapy18.1

[back to top]

Progression Free Survival (PFS)

PFS is defined as the time from enrollment to the first documented disease progression or death due to any cause, whichever occurs first as assessed by investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1). The Kaplan-Meier estimate of median PFS using the product-limit (Kaplan-Meier) method for censored data is presented. (NCT03664024)
Timeframe: Up to ~36 months

InterventionMonths (Median)
Pembrolizumab Plus Platinum-doublet Chemotherapy7.2

[back to top]

Tumor Mutation Burden (TMB) in Cell-free Circulating Tumor Deoxyribonucleic Acid (ctDNA)

Cell-free ctDNA allows the exploration of tumor features from blood samples. TMB is a measure of mutational load in tumor cells and expressed as the number of somatic mutations per megabase (mut/MB) of DNA. The mean TMB in cell-free ctDNA of participants is presented. (NCT03664024)
Timeframe: Baseline (Day 1)

InterventionMut/MB (Mean)
Pembrolizumab Plus Platinum-doublet Chemotherapy Overall9
Pembrolizumab Plus Platinum-doublet Chemotherapy Responder8
Pembrolizumab Plus Platinum-doublet Chemotherapy Non-responder10

[back to top]

Percentage of Participants Who Experienced One or More Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experienced an AE is presented. (NCT03664024)
Timeframe: Up to ~31 months

InterventionPercentage of Participants (Number)
Pembrolizumab Plus Platinum-doublet Chemotherapy100

[back to top]

Percentage of Participants Discontinuing Study Intervention Due to an AE.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who discontinued the study intervention due to an AE is presented. (NCT03664024)
Timeframe: Up to ~28 months

InterventionPercentage of Participants (Number)
Pembrolizumab Plus Platinum-doublet Chemotherapy38.5

[back to top]

Objective Response Rate

Objective response rate is the proportion of participants who have a confirmed complete response (CR) or partial response (PR). Objective response rate is assessed by investigator review according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants with missing data are considered non-responders. The percentage of participants with an ORR is presented. (NCT03664024)
Timeframe: Up to ~25 months

InterventionPercentage of Participants (Number)
Pembrolizumab Plus Platinum-doublet Chemotherapy40.2

[back to top]

Part A: Time to Progression (TTP)

TTP according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and assessed by an Investigator was defined as the time from first dose of study intervention until progression disease (PD). PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Participant wise data reported for this outcome measure. (NCT03704467)
Timeframe: Time from first dose of study treatment up to 230 days

Interventionmonths (Number)
Participant 1Participant 2
Part A: Carboplatin + M6620 + Avelumab1.92.1

[back to top]

Part A: Progression-Free Survival (PFS)

PFS according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as the time from date of randomization until date of the first observation of progressive disease (PD) or death due to any cause within 12 weeks of the last tumor assessment in the absence of documented PD, whichever occurs first. PD was defined as at least a 20% increase in the sum of longest diameter (SLD), taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Participant wise data reported for this outcome measure. (NCT03704467)
Timeframe: Time from first dose of study treatment up to 230 days

Interventionmonths (Number)
Participant 1Participant 2Participant 3
Part A: Carboplatin + M6620 + Avelumab1.92.16.1

[back to top] [back to top]

Part A: Number of Participants With Confirmed Best Overall Response (BOR)

Confirmed BOR according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and as assessed by an Investigator was defined as best response of any of the complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) recorded from the date of randomization until disease progression/ recurrence (taking the smallest measurement recorded since the start of treatment as reference). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. SD: Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD was defined as at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions and unequivocal progression of non-target lesions. Number of participants with BOR in each category (CR, PR, SD, PD) were reported. (NCT03704467)
Timeframe: Time from first dose of study treatment up to 230 days

InterventionParticipants (Count of Participants)
Complete ResponsePartial ResponseStable DiseaseProgressive Disease
Part A: Carboplatin + M6620 + Avelumab0012

[back to top]

Part A: Number of Participants With Dose Limiting Toxicities (DLTs)

DLT: any death not clearly due to underlying disease/extraneous causes/Grade(Gr) >=3 nonhematologic/Gr>=4 hematologic toxicity that was probably/definitely related to any of study interventions, individually/combination that occurred during DLT observation period, except for any of following: Gr3 infusion-related reaction; Transient (<=6hr) Gr3 flu-like symptoms/fever, controlled with medical management; Transient (<=72hr) Gr3 fatigue, local reactions, headache, nausea/emesis; Gr3 diarrhea, skin toxicity, liver function test increase; Single laboratory values out of normal range and controlled with medical management; Tumor flare phenomenon: local pain, irritation/rash, localized at sites of known/suspected tumor; Neutropenia (Gr3/4) for <7 days not associated with any infection; Gr3 thrombocytopenia for <7 days without clinically significant bleeding and not requiring platelet transfusion; Symptomatic thyroid dysfunction manageable with treatment. (NCT03704467)
Timeframe: Up to 3 weeks

InterventionParticipants (Count of Participants)
Part A: Carboplatin + M6620 + Avelumab0

[back to top]

Disease Control Rate

Disease control rate will include complete response (CR], partial response (PR), and stable disease (SD), as per RECIST v1.1 criteria. (NCT03713944)
Timeframe: From C1D1 until death or up to a maximum of 28 months

Interventionpercentage of participants (Number)
Arm A92.9

[back to top]

Progression Free Survival

Progression free survival (PFS) defined as the time from the initiation of treatment to the time when the criteria for disease progression is met as defined by RECIST v1.1 or death of any cause.Disease progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions (NCT03713944)
Timeframe: From C1D1 until progression or death up to maximum of 20 Months

Interventionmonths (Median)
Arm A11.3

[back to top]

Number of Participants With Adverse Events

To characterize the toxicity of carboplatin plus pemetrexed plus atezolizumab plus bevacizumab in immunotherapy and chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5. (NCT03713944)
Timeframe: From C1D1 up to a maximum of 20 Months or until death

InterventionParticipants (Count of Participants)
Patient had at least one adverse event of any gradePatient had at least one grade 3 or greater adverse eventPatient had at least one grade 3 or greater treatment related adverse eventPatient had serious adverse event
Arm A30241912

[back to top]

Overall Response Rate

"Overall Response rate will include confirmed complete response (CR) + confirmed partial response (PR), as determined as per RECIST v1.1 criteria and assessed by the local investigator or designee.~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR." (NCT03713944)
Timeframe: From C1D1 until death or up to a maximum of 28 months.

Interventionpercentage of participants (Number)
Arm A42.9

[back to top]

Overall Survival

To estimate the overall survival (OS) of carboplatin plus pemetrexed plus atezolizumab plus bevacizumab in immunotherapy and chemotherapy-naïve patients with stage IV non-squamous non-small cell lung cancer. (NCT03713944)
Timeframe: From C1D1 up to a maximum of 28 Months or until death

Interventionmonths (Median)
Arm A22.4

[back to top]

Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

Progression free survival (PFS) is defined as the time (in months) from first treatment day to the date of the first documentation of objective progression of disease (PD) according to RECIST version 1.1 assessed by Investigator, or death due to any cause, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. (NCT03717155)
Timeframe: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 737 days)

InterventionMonths (Median)
Avelumab and Cetuximab6.1

[back to top]

Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator

Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported. (NCT03717155)
Timeframe: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)

Interventionpercentage of participants (Number)
Avelumab and Cetuximab34.9

[back to top]

Serum Trough Concentration Levels (Ctrough) of Avelumab

Ctrough is the serum concentration observed immediately before next dosing. (NCT03717155)
Timeframe: Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337

Interventionmcg/mL (Geometric Mean)
Day 8Day 22Day 29Day 43Day 50Day 64Day 71Day 85Day 99Day 113Day 127Day 169Day 253Day 337
Avelumab and Cetuximab28.813.642.415.656.419.758.221.521.219.418.119.317.020.8

[back to top]

Serum Trough Concentration Levels (Ctrough) of Cetuximab

Ctrough is the serum concentration observed immediately before next dosing. (NCT03717155)
Timeframe: Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337

Interventionmcg/mL (Geometric Mean)
Day 8Day 22Day 29Day 43Day 50Day 64Day 71Day 85Day 99Day 113Day 127Day 169Day 253Day 337
Avelumab and Cetuximab12.112.822.825.623.917.235.426.522.635.038.040.431.928.9

[back to top] [back to top]

Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab

Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed cetuximab concentration-time data. (NCT03717155)
Timeframe: Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337

Interventionmcg/mL (Geometric Mean)
Day 1Day 8Day 22Day 29Day 43Day 50Day 64Day 71Day 85Day 99Day 113Day 127Day 169Day 253Day 337
Avelumab and Cetuximab109198124260154238159262239252250245297269304

[back to top]

Overall Survival (OS)

OS is defined as the time from the first treatment day to the date of death due to any cause. Overall survival was assessed using Kaplan-Meier analysis. (NCT03717155)
Timeframe: Time from the first dose of study drug until occurrence of death due to any cause (assessed up to 941 days)

InterventionMonths (Median)
Avelumab and Cetuximab10.1

[back to top]

Number of Participants With Positive Anti-Drug Antibody (ADA) of Cetuximab

The detection of antibodies to cetuximab was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of cetuximab were reported. (NCT03717155)
Timeframe: Pre-dose up to 149 days

InterventionParticipants (Count of Participants)
Avelumab and Cetuximab1

[back to top]

Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab

The detection of antibodies to avelumab was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of avelumab were reported. (NCT03717155)
Timeframe: Pre-dose up to 149 days

InterventionParticipants (Count of Participants)
Avelumab and Cetuximab7

[back to top]

Duration of Response (DOR)

DOR is defined for participants with confirmed complete response (CR) or partial response (PR), as the time from first documentation of confirmed response to the date of first documentation of progression of disease (PD) according to RECIST version 1.1 (assessed by Investigator) or death due to any cause or tumor assessment. Duration of objective response was assessed using Kaplan-Meier analysis. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. (NCT03717155)
Timeframe: Time from the first dose of study drug until occurrence of PD, death due to any cause or last tumor assessment (assessed up to 612 days)

InterventionMonths (Median)
Avelumab and Cetuximab7.1

[back to top]

Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab

Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed Avelumab concentration-time data. (NCT03717155)
Timeframe: Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337

Interventionmicrogram per milliliter (mcg/mL) (Geometric Mean)
Day 1Day 8Day 22Day 29Day 43Day 50Day 64Day 71Day 85Day 99Day 113Day 127Day 169Day 253Day 337
Avelumab and Cetuximab206243234282237259214244223202234222245249246

[back to top]

Number of Participants With Adverse Events as a Measure of Safety and Tolerability of Carboplatin + Gemcitabine or Docetaxel

Assess the safety and tolerability of the combination of atezolizumab plus chemotherapy (carboplatin + gemcitabine or docetaxel) using CTCAE v4.03. Number of subjects who had any adverse events or events greater than grade 3 were reported in this outcome measure. (NCT03737123)
Timeframe: From C1D1 until death or up to a maximum of 8 months

InterventionParticipants (Count of Participants)
Number of patients had at least one adverse event of any gradeNumber of patients had at least one grade 3 or greater adverse eventNumber of patients had at least one grade 3 or greater treatment related adverse eventNumber of patients having serious adverse event
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine6663

[back to top]

Progression Free Survival (PFS) for Atezolizumab + Carboplatin and Gemcitabine

Evaluate PFS for atezolizumab + carboplatin and gemcitabine. PFS defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. (NCT03737123)
Timeframe: From C1D1 until death or progression or up to a maximum of 26 months

Interventionmonths (Median)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.3

[back to top]

Clinical Benefit Rate (CBR) With RECIST 1.1

Clinical benefit rate (CBR) of treatment (defined by proportion of all subjects with stable disease for at least 3 months, partial response, or complete response) using RECIST 1.1 from the start of treatment until disease/recurrence(taking as reference for progressive disease the smallest measurements recorded since the start of treatment). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions, neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the treatment started; Clinical Benefit Rate (CBR) = CR +PR +SD (for atleast 3 months). (NCT03737123)
Timeframe: From C1D1 until death or up to a maximum of 28 months.

Interventionpercentage of participants (Number)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine100

[back to top]

Clinical Benefit Rate (CBR) With irRECIST

"Clinical benefit rate (CBR) of treatment (defined by proportion of all subjects with stable disease for at least 3 months, partial response, or complete response) using irRECIST from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).~Per irRECIST for target lesions: Complete Response (irCR), Disappearance of all target lesions; Partial Response (irPR), >=30% decrease in the sum of the longest diameter of target lesions, neither sufficient shrinkage to qualify for irPR nor sufficient increase to qualify for irPD, taking as reference the smallest sum longest diameter since the treatment started; Clinical Benefit Rate (CBR) = irCR +irPR +irSD (for atleast 3 months)." (NCT03737123)
Timeframe: From C1D1 until death or up to a maximum of 28 months.

Interventionpercentage of participants (Number)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine100

[back to top]

Overall Survival (OS)

OS defined by the date of treatment start to date of death from any cause. (NCT03737123)
Timeframe: From C1D1 until death or up to a maximum of 28 months

Interventionmonths (Median)
Phase IIA : Atezolizumab + Carboplatin + GemcitabineNA

[back to top]

Objective Response Rate (ORR) With irRECIST

"ORR defined as the proportion of all subjects with confirmed PR or CR using immunerelated response criteria (irRECIST), from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).~Per irRECIST for target lesions Complete Response (irCR), Disappearance of all target lesions; Partial Response (irPR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = irCR + irPR." (NCT03737123)
Timeframe: From C1D1 until death or up to a maximum of 28 months.

Interventionpercentage of participants (Number)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine40

[back to top]

Objective Response Rate (ORR) With RECIST 1.1

"Objective response rate (ORR) using RECIST 1.1 defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment).~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR" (NCT03737123)
Timeframe: From C1D1 until death or up to a maximum of 28 months.

Interventionpercentage of participants (Number)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine40

[back to top]

PFS by irRECIST

PFS defined as duration from date of treatment start until progression according to irRECIST criteria or death from any cause. Per irRECIST criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions. (NCT03737123)
Timeframe: From C1D1 until progression or death or up to a maximum of 26 months

Interventionmonths (Median)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.3

[back to top]

Progression Free Survival (PFS)

"Evaluate PFS among patients to be treated with atezolizumab in combination with carboplatin + gemcitabine or docetaxel, who have cisplatin-ineligible metastatic urothelial carcinoma and who have progressed on prior PD-1 or PD-L1 inhibitor. PFS defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.~Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions." (NCT03737123)
Timeframe: From C1D1 until progression or death or up to a maximum of 26 months

Interventionmonths (Median)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.3

[back to top]

Progression Free Survival (PFS) Compared to Historical Controls

"To compare Progression Free Survival(PFS) with the historical control, Null hypothesis - Patients receiving atezolizumab plus chemotherapy (carboplatin +gemcitabine or docetaxel) will have a median PFS of 4 months.~Alternative hypothesis - Patients receiving atezolizumab plus chemotherapy (carboplatin + gemcitabine or docetaxel) will have a median PFS of 7.2 months.~Progression Free Survival defined as duration from date of treatment start until progression according to RECIST 1.1 criteria, or death from any cause.Per RECIST 1.1 criteria, Progressive disease can be defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions." (NCT03737123)
Timeframe: From C1D1 until progression or death or up to a maximum of 26 months

Interventionmonths (Median)
Phase IIA : Atezolizumab + Carboplatin + Gemcitabine11.3

[back to top]

Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria

"ORR= number of subjects with best overall response (BOR) of complete or partial response (CR, PR) divided by number of evaluable subjects. BOR= best response recorded from start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.~CR: disappearance of target and non-target lesions; no new lesions; pathological lymph nodes < 10mm.~PR: 30% decrease in target lesions; non-target lesions not progressed or not evaluated; no new lesions.~PD: 20% increase of target lesions and/or new lesion(s).~ORR was to be compared using Fisher's exact test within each ALK inhibitor treatment arm (each mutation vs. no mutation) and also within the subset of subjects with no mutation comparing each experimental arm vs. pemetrexed. Due to early accrual closure (few subjects), only the number of subjects with BOR of CR or PR are provided, by mutation, no statistical testing. Analysis was to occur after each patient was potentially followed ≥ 24 weeks." (NCT03737994)
Timeframe: Baseline to 24 weeks

InterventionParticipants (Count of Participants)
Mutation = None: BOR of CR or PR
Ensartinib0

[back to top]

Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria

"ORR= number of subjects with best overall response (BOR) of complete or partial response (CR, PR) divided by number of evaluable subjects. BOR= best response recorded from start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.~CR: disappearance of target and non-target lesions; no new lesions; pathological lymph nodes < 10mm.~PR: 30% decrease in target lesions; non-target lesions not progressed or not evaluated; no new lesions.~PD: 20% increase of target lesions and/or new lesion(s).~ORR was to be compared using Fisher's exact test within each ALK inhibitor treatment arm (each mutation vs. no mutation) and also within the subset of subjects with no mutation comparing each experimental arm vs. pemetrexed. Due to early accrual closure (few subjects), only the number of subjects with BOR of CR or PR are provided, by mutation, no statistical testing. Analysis was to occur after each patient was potentially followed ≥ 24 weeks." (NCT03737994)
Timeframe: Baseline to 24 weeks

InterventionParticipants (Count of Participants)
Mutation = I1171: BOR of CR or PR
LDK378 (Ceritinib)0

[back to top]

Duration of Overall Response, Per Investigator Assessment Using RECIST v1.1

"Duration of overall response (DOR) is defined as the time from the first occurrence of a documented BOR of CR or PR to the first date of recorded disease progression (PD) or death from any cause (whichever occurs first). BOR is the best response recorded from the start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.~CR: disappearance of target and non-target lesions; no new lesions; pathological lymph nodes < 10mm.~PR: 30% decrease in target lesions; non-target lesions not progressed or not evaluated; no new lesions.~PD: 20% increase of target lesions and/or new lesion(s).~Median DOR was to be estimated, with 95% confidence intervals, for each mutation/regimen combination using the Kaplan-Meier method. Due to early accrual closure resulting in few subjects, only the mean and range DOR are provided, by mutation, and no statistical testing was done." (NCT03737994)
Timeframe: Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

Interventionmonths (Mean)
Mutation = I1171Mutation = None
Lorlatinib27.919.2

[back to top]

Duration of Overall Response, Per Investigator Assessment Using RECIST v1.1

"Duration of overall response (DOR) is defined as the time from the first occurrence of a documented BOR of CR or PR to the first date of recorded disease progression (PD) or death from any cause (whichever occurs first). BOR is the best response recorded from the start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.~CR: disappearance of target and non-target lesions; no new lesions; pathological lymph nodes < 10mm.~PR: 30% decrease in target lesions; non-target lesions not progressed or not evaluated; no new lesions.~PD: 20% increase of target lesions and/or new lesion(s).~Median DOR was to be estimated, with 95% confidence intervals, for each mutation/regimen combination using the Kaplan-Meier method. Due to early accrual closure resulting in few subjects, only the mean and range DOR are provided, by mutation, and no statistical testing was done." (NCT03737994)
Timeframe: Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

Interventionmonths (Mean)
Mutation = None
Brigatinib3.5

[back to top]

Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria

Progression-free survival time is defined as the time from second step registration to the date of the first disease progression / progressive disease (PD), death, or last known follow-up (censored). Progressive disease is defined as a 20% increase of target lesions and/or new lesion(s). Percentage of participants progression-free at a given time (PFS) was to be estimated by the Kaplan-Meier method. Median PFS and PFS at specific time points was to be reported, with 95% confidence intervals, for each mutation (or no mutation)/regimen combination. Due to early accrual closure resulting in few participants, only the number of participants who progressed or died, by mutation, with no statistical testing. (NCT03737994)
Timeframe: Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

InterventionParticipants (Count of Participants)
Mutation = I1107: progression or death
LDK378 (Ceritinib)0

[back to top]

Overall Survival (OS)

Survival time is defined as the time from second step registration to the date of death, or last known follow-up (censored). Percentage of participants alive at a given time (OS) was to be estimated by the Kaplan-Meier method. Median OS and OS at specific time points was to be reported, with 95% confidence intervals, for each mutation/regimen combination. Due to early accrual closure resulting in few patients, only the number of participants who died are provided, by mutation, and no statistical testing was done. (NCT03737994)
Timeframe: Baseline to the date of death or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

,
InterventionParticipants (Count of Participants)
Mutation = I1171: deathsMutation = None: deaths
Brigatinib01
Lorlatinib00

[back to top]

Objective Response Rate (ORR), Per Investigator Assessment Using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 Criteria

"ORR= number of subjects with best overall response (BOR) of complete or partial response (CR, PR) divided by number of evaluable subjects. BOR= best response recorded from start of treatment to first progression (PD)/new anticancer therapy, otherwise last follow-up.~CR: disappearance of target and non-target lesions; no new lesions; pathological lymph nodes < 10mm.~PR: 30% decrease in target lesions; non-target lesions not progressed or not evaluated; no new lesions.~PD: 20% increase of target lesions and/or new lesion(s).~ORR was to be compared using Fisher's exact test within each ALK inhibitor treatment arm (each mutation vs. no mutation) and also within the subset of subjects with no mutation comparing each experimental arm vs. pemetrexed. Due to early accrual closure (few subjects), only the number of subjects with BOR of CR or PR are provided, by mutation, no statistical testing. Analysis was to occur after each patient was potentially followed ≥ 24 weeks." (NCT03737994)
Timeframe: Baseline to 24 weeks

,
InterventionParticipants (Count of Participants)
Mutation = I1171: BOR of CR or PRMutation = None: BOR of CR or PR
Brigatinib01
Lorlatinib12

[back to top]

Overall Survival (OS)

Survival time is defined as the time from second step registration to the date of death, or last known follow-up (censored). Percentage of participants alive at a given time (OS) was to be estimated by the Kaplan-Meier method. Median OS and OS at specific time points was to be reported, with 95% confidence intervals, for each mutation/regimen combination. Due to early accrual closure resulting in few patients, only the number of participants who died are provided, by mutation, and no statistical testing was done. (NCT03737994)
Timeframe: Baseline to the date of death or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

InterventionParticipants (Count of Participants)
Mutation = None: deaths
Ensartinib2

[back to top]

Number of Participants by Highest Grade Adverse Event Reported

Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data. (NCT03737994)
Timeframe: Baseline to the date of last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

InterventionParticipants (Count of Participants)Participants (Count of Participants)
Mutation = I110772512695Mutation = I110772512697Mutation = I110772512700Mutation = none72512697Mutation = none72512695Mutation = none72512698
Grade 1Grade 2Grade 3Grade 4Grade 5
Lorlatinib1
LDK378 (Ceritinib)1
LDK378 (Ceritinib)0
Brigatinib0
Lorlatinib0
Lorlatinib2
Ensartinib3
Brigatinib1
Ensartinib0

[back to top]

Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria

Progression-free survival time is defined as the time from second step registration to the date of the first disease progression / progressive disease (PD), death, or last known follow-up (censored). Progressive disease is defined as a 20% increase of target lesions and/or new lesion(s). Percentage of participants progression-free at a given time (PFS) was to be estimated by the Kaplan-Meier method. Median PFS and PFS at specific time points was to be reported, with 95% confidence intervals, for each mutation (or no mutation)/regimen combination. Due to early accrual closure resulting in few participants, only the number of participants who progressed or died, by mutation, with no statistical testing. (NCT03737994)
Timeframe: Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

,
InterventionParticipants (Count of Participants)
Mutation = I1107: progression or deathMutation = none: progression or death
Brigatinib11
Lorlatinib01

[back to top]

Progression-free Survival (PFS), Per Investigator Assessment Using RECIST v1.1 Criteria

Progression-free survival time is defined as the time from second step registration to the date of the first disease progression / progressive disease (PD), death, or last known follow-up (censored). Progressive disease is defined as a 20% increase of target lesions and/or new lesion(s). Percentage of participants progression-free at a given time (PFS) was to be estimated by the Kaplan-Meier method. Median PFS and PFS at specific time points was to be reported, with 95% confidence intervals, for each mutation (or no mutation)/regimen combination. Due to early accrual closure resulting in few participants, only the number of participants who progressed or died, by mutation, with no statistical testing. (NCT03737994)
Timeframe: Baseline to the date of the first disease progression / progressive disease, death, or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

InterventionParticipants (Count of Participants)
Mutation = none: progression or death
Ensartinib2

[back to top]

Overall Survival (OS)

Survival time is defined as the time from second step registration to the date of death, or last known follow-up (censored). Percentage of participants alive at a given time (OS) was to be estimated by the Kaplan-Meier method. Median OS and OS at specific time points was to be reported, with 95% confidence intervals, for each mutation/regimen combination. Due to early accrual closure resulting in few patients, only the number of participants who died are provided, by mutation, and no statistical testing was done. (NCT03737994)
Timeframe: Baseline to the date of death or last known follow-up. Maximum follow-up time was 33.6 months, median 8.9 months.

InterventionParticipants (Count of Participants)
Mutation = I1171: deaths
LDK378 (Ceritinib)0

[back to top]

Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13

"Disease-related symptoms assessed by change from baseline (for maintenance phase) in EORTC QLQ-LC13. Average adjusted mean over first 11 cycles is presented.~The EORTC QLQ-LC13 was scored according to the published scoring manual. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales in the EORTC QLQ-LC13. Higher scores on symptom scales represent greater symptom severity." (NCT03775486)
Timeframe: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months

,
Interventionchange from baseline score (Mean)
EORTC QLQ-LC13: DyspnoeaEORTC QLQ-LC13: CoughingEORTC QLQ-LC13: Pain in chest
Durvalumab/Olaparib Combination Therapy-1.27-2.141.31
Durvalumab/Placebo Therapy-0.76-3.093.57

[back to top]

Concentration of Durvalumab

Concentration (pharmacokinetics) of durvalumab (NCT03775486)
Timeframe: Assessed from start of initial therapy up to 2 years.

,
Interventionμg/mL (Geometric Mean)
Cycle 01 Day 01 (Initial Therapy Phase) Post doseCycle 02 Day 01 (Initial Therapy Phase) Pre doseCycle 04 Day 01 (Initial Therapy Phase) Pre doseCycle 01 (Maintenance Phase) Post doseCycle 02 (Maintenance Phase) Pre doseCycle 05 (Maintenance Phase) Pre doseCycle 08 (Maintenance Phase) Pre doseCycle 11 (Maintenance Phase) Pre doseCycle 14 (Maintenance Phase) Pre doseCycle 17 (Maintenance Phase) Pre doseCycle 20 (Maintenance Phase) Pre doseMonth 03 (Maintenance Phase) Pre dose
Durvalumab/Olaparib Combination Therapy417.15276.812155.461535.078159.157166.644198.932210.794276.612264.096528.04612.289
Durvalumab/Placebo Therapy453.72476.959154.947524.306160.315147.848154.057186.092182.042217.137112.27612.769

[back to top]

Duration of Response

"Duration of response (DoR) defined as time from the date of first documented response following randomization until the first date of documented progression or death in the absence of disease progression.~Percentage of participants remaining in response at 3, 6, 9 and 12 months estimated using the Kaplan-Meier method." (NCT03775486)
Timeframe: From date of first documented response until objective radiological disease progression or death, up to 18 months.

,
Interventionpercent (Number)
Percentage of participants remaining in response at 3 monthsPercentage of participants remaining in response at 6 monthsPercentage of participants remaining in response at 9 monthsPercentage of participants remaining in response at 12 months
Durvalumab/Olaparib Combination Therapy90.579.169.269.2
Durvalumab/Placebo Therapy85.165.765.765.7

[back to top]

Overall Survival

"Overall survival (OS) across the maintenance phase.~OS is defined as time from date of randomization until the date of death by any cause" (NCT03775486)
Timeframe: From randomization until the date of death due to any cause, up to 18 months.

,
InterventionParticipants (Count of Participants)
DeathCensored participants (still in survival at follow up or terminated study prior to death)
Durvalumab/Olaparib Combination Therapy4490
Durvalumab/Placebo Therapy4590

[back to top]

Progression-free Survival

"Progression-free survival (PFS) based on investigator assessments according to Response Evaluation Criteria in Solid Tumours version 1.1.~PFS is defined as time from date of randomization until the date of objective radiological disease progression using Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1) or death (by any cause in the absence of progression)." (NCT03775486)
Timeframe: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months

,
InterventionParticipants (Count of Participants)
RECIST progression: Target LesionsRECIST progression: Non Target LesionsRECIST progression: New LesionsDeath in the absence of progressionCensored subjects: Censored RECIST progressionCensored subjects: Censored deathCensored subjects: Progression-free at time of analysisCensored subjects: Progression-free prior to lost to follow-upCensored subjects: Progression-free prior to withdrawal of consentCensored subjects: Progression-free prior to discontinuation due to other reasonCensored subjects: No post-baseline evaluable tumor assessment
Durvalumab/Olaparib Combination Therapy402844801440302
Durvalumab/Placebo Therapy633039900340202

[back to top]

Time to Deterioration in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13

"Disease-related symptoms assessed by time to deterioration (for maintenance phase) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-Lung Cancer (LC)13.~Symptom deterioration is defined as an increase in the score from baseline of less than or equal to 10) that is confirmed at a subsequent assessment, or death (by any cause) in the absence of a clinically meaningful symptom deterioration.~NA is not applicable. The upper confidence limit was not calculable because of an insufficient number of participants with events." (NCT03775486)
Timeframe: From randomization until date of objective radiological disease progression or death, or last evaluable assessment in the absence of progression, up to 18 months

,
Interventionmonths (Median)
EORTC QLQ-LC13: DyspnoeaEORTC QLQ-LC13: CoughingEORTC QLQ-LC13: HaemoptysisEORTC QLQ-LC13: Pain In ChestEORTC QLQ-LC13: Pain In Arm Or ShoulderEORTC QLQ-LC13: Pain In Other Parts
Durvalumab/Olaparib Combination Therapy10.011.715.013.815.010.3
Durvalumab/Placebo Therapy9.710.612.611.59.710.6

[back to top] [back to top] [back to top]

Time to Deterioration in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30

"Disease-related symptoms and health-related quality of life (HRQoL) assessed by time to deterioration (for maintenance phase) in EORTC QLQ-C30.~NA is not applicable. The upper confidence limit was not calculable because of an insufficient number of participants with events." (NCT03775486)
Timeframe: From randomization until date of first symptom deterioration that is confirmed, up to 18 months.

,
Interventiontime to deterioration (months) (Median)
EORTC QLQ-C30: FatigueEORTC QLQ-C30: Nausea And VomitingEORTC QLQ-C30: PainEORTC QLQ-C30: DyspnoeaEORTC QLQ-C30: InsomniaEORTC QLQ-C30: Appetite LossEORTC QLQ-C30: ConstipationEORTC QLQ-C30: DiarrhoeaPhysical FunctioningRole FunctioningEmotional FunctioningCognitive FunctioningSocial FunctioningGlobal Health Status/Quality of Life
Durvalumab/Olaparib Combination Therapy8.812.210.212.213.811.712.213.812.010.012.210.29.310.2
Durvalumab/Placebo Therapy1012.69.711.010.611.512.011.512.010.611.010.610.09.7

[back to top]

Presence of Anti-drug Antibodies (ADAs) for Durvalumab

Presence of anti-drug antibodies (ADAs) for durvalumab, as assessed at 3, 6, 12, 16 and 20 weeks after start of treatment and every 12 weeks thereafter until 3 and 6 months after last dose of durvalumab (NCT03775486)
Timeframe: Assessed from start of initial therapy up to 2 years.

,
InterventionParticipants (Count of Participants)
ADA prevalence (any ADA positive, baseline or post-baseline)ADA incidence (treatment-induced or treatment-boosted)ADA positive post-baseline and positive at baselineADA positive post-baseline and not detected at baseline (treatment-induced)ADA not detected at post-baseline and positive at baselineTreatment-boosted ADAPersistent positiveTransient positiveNeutralizing anti-drug antibody positive at any visit
Durvalumab/Olaparib Combination Therapy1150560051
Durvalumab/Placebo Therapy941440321

[back to top]

Change From Baseline in EORTC Quality of Life Questionnaire (QLQ) QLQ-C30

"Disease-related symptoms and health-related quality of life (HRQoL) assessed by change from baseline (for maintenance phase) in EORTC QLQ-C30. Average adjusted mean over first 11 cycles is presented.~The EORTC QLQ-C30 was scored according to the published scoring manual. An outcome variable consisting of a score from 0 to 100 was derived for each of the symptom scales, each of the function scales, and the global health status/QoL scale in the EORTC QLQ-C30. Higher scores on the global health status and function scales indicate better health status/function.~A high scale score represents a higher response level. Thus a high score for a functional scale represents a high / healthy level of functioning, a high score for the global health status / quality of life (QoL) represents a high QoL, but a high score for a symptom scale / item represents a high level of symptomatology / problems." (NCT03775486)
Timeframe: Includes all assessments occurring within the first 12 months of randomization or until disease progression, up to 18 months.

,
Interventionchange from baseline score (Mean)
EORTC QLQ-C30: FatigueEORTC QLQ-C30: Appetite loss
Durvalumab/Olaparib Combination Therapy0.15-0.13
Durvalumab/Placebo Therapy-1.49-3.35

[back to top]

Overall RECIST 1.1 Response Rate

Response rate determined according to RECIST 1.1 criteria (NCT03780010)
Timeframe: 6 months

,
InterventionParticipants (Count of Participants)
Stable Disease Best ResponsePartial Response Best ResponseProgressive Disease Best ResponseComplete Response Best Response
10 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin9300
8 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin2100

[back to top]

Median Progression Free Survival

Median duration of progression free survival according to RECIST 1.1 criteria (NCT03780010)
Timeframe: months

InterventionMonths (Median)
8 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin3
10 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin6.5

[back to top]

Percent of Patients With Progression-free Survival (PFS) at 6 Months

Number of patients with progression-free survival at 6 months determined according to RECIST 1.1 criteria (NCT03780010)
Timeframe: 6 months

InterventionParticipants (Count of Participants)
8 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin1
10 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin7

[back to top]

Pharmacokinetic Profile of TRC105 When Given With Bevacizumab and Paclitaxel/Carboplatin

Trough serum TRC105 pharmacokinetic concentrations at steady state (cycle 3 day 1) will be measured using validated ELISA methods. (NCT03780010)
Timeframe: 3 months

Interventionng/mL (Mean)
8 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin56600
10 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin103228

[back to top]

Treatment-Emergent Adverse Events

Incidence of treatment-emergent (i.e. TRC105, bevacizumab, paclitaxel and/or carboplatin) adverse events by CTCAE v4.03 (NCT03780010)
Timeframe: from screening until completion of follow-up, on average 6 months

,
InterventionParticipants (Count of Participants)
Participants who experienced an AEParticipants who experienced a TRC105 related AEParticipants who experienced a Bev related AEParticipants who experienced a Carbo related AEParticipants who experienced a Pac related AE
10 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin1211101212
8 mg/kg TRC105 + Bevacizumab + Paclitaxel/Carboplatin33333

[back to top]

"Percentage of Participants Who Are Feasibility Failure"

"Feasibility failures were defined as patients that did not receive >= 75% of the planned dinutuximab doses during Induction cycles 3-5. Assessed by estimation of the feasibility failure rate together with a 95% confidence interval." (NCT03786783)
Timeframe: Up to the first 5 cycles of treatment

InterventionPercentage of patients (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)0.0

[back to top]

Response Rate

Per the revised INRC, response is comprised by responses in 3 components: primary tumor, soft tissue and bone metastases, and bone marrow. Primary and metastatic soft tissue sites were assessed using Response Evaluation Criteria in Solid Tumors and MIBG scans or FDG-PET scans if the tumor was MIBG non-avid. Bone marrow was assessed by histology or immunohistochemistry and cytology or immunocytology. Complete response (CR) - All components meet criteria for CR. Partial response (PR) - PR in at least one component and all other components are either CR, minimal disease (in bone marrow), PR (soft tissue or bone) or not involved (NI; no component with progressive disease (PD). Minor response (MR) - PR or CR in at least one component but at least one other component with stable disease; no component with PD. Stable disease (SD) - Stable disease in one component with no better than SD or NI in any other component; no component with PD. Progressive disease (PD) - Any component with PD. (NCT03786783)
Timeframe: Up to the first 5 cycles of treatment

InterventionPercentage of patients (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)78.6

[back to top]

Percentage of Participants With Unacceptable Toxicity

Assessed with National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Assessed by estimation of the combined toxic death and unacceptable toxicity rate during Induction cycles 3-5 together with a 95% confidence interval. (NCT03786783)
Timeframe: Up to the first 5 cycles of treatment

Interventionpercentage of patients (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)0.0

[back to top]

Event-free Survival

Per the revised INRC, progressive disease is: 1) > 20% increase in the longest diameter of the primary tumor, taking as reference the smallest sum and ¬> increase of 5 mm in longest dimension, 2) Any new soft tissue lesion detected by CT/MRI that is MIBG avid or FDG-PET avid, 3) Any new soft tissue lesion seen on CT/MRI that is biopsied and found to be neuroblastoma or ganglioneuroblastoma, 4) Any new bone site that is MIBG avid, 5) Any new bone site that is FDG-PET avid and has CT/MRI findings of tumor or is histologically neuroblastoma or ganglioneuroblastoma 6) A metastatic soft tissue site with > 20% increase in longest diameter, taking as reference the smallest sum on study, and with > 5mm in sum of diameters of target soft tissue lesions, 7) A relative MIBG score ¬> 1.2, 8) Bone marrow without tumor infiltration that becomes >5% tumor infiltration, 9) Bone marrow with tumor infiltration that increases by > 2-fold and has > 20% tumor infiltration on reassessment. (NCT03786783)
Timeframe: Up to 1 year

InterventionPercent Probability (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)82.6

[back to top]

Overall Survival

Kaplan-Meier method was used to estimate overall survival (OS). OS was defined as the time from study enrollment to death. 1-year OS is provided. (NCT03786783)
Timeframe: Up to 1 year

InterventionPercent Probability (Number)
Treatment(Chemotherapy, Dinutuximab, Sargramostim, ASCT, EBRT)95.0

[back to top]

Overall Survival (Duration)

Time from the date of randomisation until death by any cause (NCT03830866)
Timeframe: Time from date of randomisation until date of death by any cause, assessed up to the data cut-off date (20th January 2022), assessed up to a maximum of 34.3 months

InterventionMonths (Median)
Durvalumab + SoC CCRTNA
Placebo + SoC CCRTNA

[back to top]

Objective Response Rate (ORR)

Percentage of evaluable patients with an Investigator-assessed visit response of complete response (CR) or partial response (PR). CR defined as disappearance of all target and non-target lesions and no new lesions. PR defined as >= 30% decrease in the sum of diameters of target lesions (compared to baseline) and no new non-target lesion (NCT03830866)
Timeframe: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months

InterventionPercentage of Participants (Number)
Durvalumab + SoC CCRT82.6
Placebo + SoC CCRT80.5

[back to top]

Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression

PFS defined as time from date of randomisation until date of tumour progression or death by any cause, regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression (NCT03830866)
Timeframe: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months

InterventionMonths (Median)
Durvalumab + SoC CCRTNA
Placebo + SoC CCRTNA

[back to top]

Progression-free Survival (PFS) Based on the Investigator Assessment According to RECIST 1.1 or Histopathologic Confirmation of Local Tumour Progression, PD-L1 Expression >= 1%

PFS defined as time from date of randomisation until date of tumour progression or death by any cause, regardless of whether the patient withdrew from randomized therapy or received another anticancer therapy prior to progression (NCT03830866)
Timeframe: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months

InterventionMonths (Median)
Durvalumab + SoC CCRTNA
Placebo + SoC CCRTNA

[back to top]

Duration of Response (DoR) in Patients With Complete Response (CR)

Time from date of first documented CR until date of documented progression or death in the absence of progression. For patients who did not progress their DoR was their Progression-free survival censoring time (NCT03830866)
Timeframe: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months

InterventionMonths (Median)
Durvalumab + SoC CCRTNA
Placebo + SoC CCRTNA

[back to top]

Complete Response Rate

Percentage of evaluable patients with an overall visit response of Complete Response (disappearance of all target and non-target lesions) (NCT03830866)
Timeframe: Tumor assessments start 20 weeks after randomisation then every 12 weeks up to 164 weeks, then every 24 weeks until date of RECIST1.1 defined radiological progression. Assessed up to date of DCO (20-Jan-2022) to a maximum of 32.6 months

InterventionPercentage of Participants (Number)
Durvalumab + SoC CCRT42.9
Placebo + SoC CCRT40.3

[back to top]

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator

PFS was defined as the time from first administration of study intervention until date of the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Kaplan-Meier estimates was used to calculate PFS. (NCT03840915)
Timeframe: Time from first administration of study drug until the first documentation of PD or death, assessed up to approximately 26 months

Interventionmonths (Median)
Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed5.0
Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel4.1
Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine5.4
Cohort D: Bintrafusp Alfa + Docetaxel2.6

[back to top]

Overall Survival (OS)

OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method. (NCT03840915)
Timeframe: Time from first treatment assessed up to approximately 26 months

Interventionmonths (Median)
Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed11.4
Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel11.8
Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + GemcitabineNA
Cohort D: Bintrafusp Alfa + Docetaxel16.5

[back to top]

Duration of Response (DOR)

DOR was defined for participants with confirmed response, as the time from first documentation of confirmed objective response (Complete Response [CR] or Partial Response [PR]) according to RECIST 1.1 to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Results were calculated based on Kaplan-Meier estimates. (NCT03840915)
Timeframe: Time from first documentation of a confirmed objective response to PD or death due to any cause (assessed up to approximately 26 months)

Interventionmonths (Median)
Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed9.6
Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxelNA
Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine10.5
Cohort D: Bintrafusp Alfa + Docetaxel3.4

[back to top]

Number of Participants With Dose-Limiting Toxicities (DLTs)

DLT was defined as Adverse Events(AEs) with any of following toxicities: Grade 4 nonhematologic toxicity or hematologic toxicity lasting more than equal to(>=) 7 days despite medical intervention; Grade 3 nausea, vomiting, and diarrhea lasting >= 3 days despite supportive care; Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for >= 7 days; Grade 3 or Grade 4: grade 3 is defined as absolute neutrophil count (ANC) less than (<) 1,000/Cubic Millimeter(mm3) with a temperature of > 38.3 degree Celsius (°C); grade 4 is defined as ANC < 1,000/mm3 with a temperature of > 38.3°C, with life-threatening consequences; Thrombocytopenia < 25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events >= Grade 3 occurring within 5 days of bintrafusp alfa treatment; Prolonged delay(> 3 weeks) in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity. (NCT03840915)
Timeframe: Day 1 Week 1 up to Week 3

InterventionParticipants (Count of Participants)
Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed1
Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel1
Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine0
Cohort D: Bintrafusp Alfa + Docetaxel3

[back to top]

Number of Participants With Positive Antidrug Antibodies (ADA)

Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported. (NCT03840915)
Timeframe: Time from first treatment assessed up to approximately 26 months

InterventionParticipants (Count of Participants)
Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed9
Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel3
Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine2
Cohort D: Bintrafusp Alfa + Docetaxel3

[back to top]

Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC)

Percentage of participants with confirmed objective response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by Investigator. (NCT03840915)
Timeframe: Time from first treatment assessed up to approximately 26 months

InterventionPercentage of Participants (Number)
Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed45.0
Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel66.7
Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine44.4
Cohort D: Bintrafusp Alfa + Docetaxel16.7

[back to top]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. (NCT03840915)
Timeframe: Time from first treatment assessed up to approximately 26 months

,,,
InterventionParticipants (Count of Participants)
TEAEsSerious TEAEs
Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed4031
Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel95
Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine96
Cohort D: Bintrafusp Alfa + Docetaxel129

[back to top]

Number of Participants Who Experienced At Least One Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented. (NCT03850444)
Timeframe: Up to 59.7 months

InterventionParticipants (Count of Participants)
Pembrolizumab126
Chemotherapy (SOC Treatment)124

[back to top]

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented. (NCT03850444)
Timeframe: Up to 56.7 months

InterventionParticipants (Count of Participants)
Pembrolizumab26
Chemotherapy (SOC Treatment)22

[back to top]

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%

OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization until death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The OS for participants with a TPS ≥20% is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionMonths (Median)
Pembrolizumab20.0
Chemotherapy (SOC Treatment)13.7

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization until the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions or progression in non-target lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants with a TPS ≥50% is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionMonths (Median)
Pembrolizumab8.3
Chemotherapy (SOC Treatment)6.5

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization until the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions or progression in non-target lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants with a TPS ≥20% is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionMonths (Median)
Pembrolizumab6.3
Chemotherapy (SOC Treatment)6.5

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization until the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions or progression in non-target lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants with a TPS ≥1% is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionMonths (Median)
Pembrolizumab6.3
Chemotherapy (SOC Treatment)6.4

[back to top]

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%

OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization until death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The OS for participants with a TPS ≥50% is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionMonths (Median)
Pembrolizumab20.0
Chemotherapy (SOC Treatment)14.0

[back to top]

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%

OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization until death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The OS for participants with a TPS ≥1% is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionMonths (Median)
Pembrolizumab20.0
Chemotherapy (SOC Treatment)13.7

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionPercentage of participants (Number)
Pembrolizumab41.7
Chemotherapy (SOC Treatment)24.3

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionPercentage of participants (Number)
Pembrolizumab35.6
Chemotherapy (SOC Treatment)24.3

[back to top]

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target and non-target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented. (NCT03850444)
Timeframe: Up to 23.2 months

InterventionPercentage of participants (Number)
Pembrolizumab32.8
Chemotherapy (SOC Treatment)24.6

[back to top]

Clinical Benefit Rate

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR; Stable disease (SD): Neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD; Progressive disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). Clinical Benefit Rate (CBR) = CR + PR + SD at 6 months. (NCT03853707)
Timeframe: Up to 6 months

Interventionpercentage of participants (Number)
Arm A (Ipatasertib, Carboplatin, Paclitaxel)20.0
Arm B (Ipatasertib and Carboplatin)41.7
Arm C (Ipatasertib, Capecitabine, Atezolizumab)50.0

[back to top]

Overall Response

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. (NCT03853707)
Timeframe: Up to 36 months

InterventionParticipants (Count of Participants)
Arm A (Ipatasertib, Carboplatin, Paclitaxel)7
Arm B (Ipatasertib and Carboplatin)2
Arm C (Ipatasertib, Capecitabine, Atezolizumab)3

[back to top]

Overall Survival (OS)

Estimated using the product-limit method of Kaplan and Meier. Failure defined as death from any cause. (NCT03853707)
Timeframe: Up to 36 months

InterventionMonths (Median)
Arm A (Ipatasertib, Carboplatin, Paclitaxel)11.2
Arm B (Ipatasertib and Carboplatin)17.0
Arm C (Ipatasertib, Capecitabine, Atezolizumab)NA

[back to top]

Progression-free Survival (PFS)

Estimated using the product-limit method of Kaplan and Meier. Failure defined as disease progression or death from any cause. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. (NCT03853707)
Timeframe: Up to 36 months

InterventionMonths (Median)
Arm A (Ipatasertib, Carboplatin, Paclitaxel)4.8
Arm B (Ipatasertib and Carboplatin)3.9
Arm C (Ipatasertib, Capecitabine, Atezolizumab)8.2

[back to top]

Disease Free Survival (DFS)

Disease free survival will be defined as the time from surgical resection until the criteria for disease recurrence is met or death as a result of any cause. Disease recurrence is return of the cancer to where it started (local) or in another part of the body (distant). (NCT03871153)
Timeframe: Time from surgical resection until disease recurrence or death, up to a maximum of 8 months

InterventionMonths (Median)
Treatment6.7

[back to top]

Assess Adverse Events (AE)

Adverse events, >= grade 3 and related to treatment will be summarized by frequency and severity according to the NCI Common Terminology Criteria for (NCI CTCAE) v5 (NCT03871153)
Timeframe: AEs had been recorded from time of signed informed consent until 90 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 13 months.

InterventionParticipants (Count of Participants)
LUNG INFECTION Grade 5HYPOKALEMIA Grade 4ACIDOSIS Grade 3APPENDICITIS Grade 3PAIN Grade 3
Treatment11111

[back to top]

Pathologic Complete Response Rate

Pathologic Complete Response Rate is defined as lack of evidence of viable cancer in the surgical specimen at the time of surgery. (NCT03871153)
Timeframe: 3 months

InterventionParticipants (Count of Participants)
Pathological Complete Response AchievedPathological Complete Response Not Achieved
Treatment04

[back to top]

Pathologic N0 Rate

Pathologic N0 rate is defined as a lack of evidence of viable cancer in the removed lymph nodes at the time of surgery. (NCT03871153)
Timeframe: 3 months

InterventionParticipants (Count of Participants)
Pathologic N0 Status AchievedPathologic N0 Status Not Achieved
Treatment31

[back to top]

Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1. ORR as assessed by blinded independent central review per RECIST 1.1 is presented. (NCT03875092)
Timeframe: Up to approximately 33 months (Database cutoff date of 30-Sep-2020)

InterventionPercentage of Participants (Number)
Pembrolizumab + Chemotherapy80.0
Chemotherapy43.3

[back to top]

Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 is presented. Data are from the product-limit (Kaplan-Meier) method for censored data. (NCT03875092)
Timeframe: Up to approximately 33 months (Database cutoff date of 30-Sep-2020)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy8.3
Chemotherapy4.2

[back to top]

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. OS is presented. Data are from the product-limit (Kaplan-Meier) method for censored data. (NCT03875092)
Timeframe: Up to approximately 39 months (Database cutoff date of 30-Sep-2020)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy30.1
Chemotherapy12.7

[back to top]

Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

For participants who demonstrated a confirmed response (Complete Response [CR]: Disappearance of all target lesions or Partial Response [PR]: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death. DOR as assessed by blinded independent central review per RECIST 1.1 is presented. (NCT03875092)
Timeframe: Up to approximately 30 months (Database cutoff date of 30-Sep-2020)

InterventionMonths (Median)
Pembrolizumab + Chemotherapy7.1
Chemotherapy3.5

[back to top]

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

The number of participants who discontinued study treatment due to an AE is presented. (NCT03875092)
Timeframe: Up to approximately 29 months (Database cutoff date of 30-Sep-2020)

InterventionParticipants (Count of Participants)
Pembrolizumab + Chemotherapy8
Chemotherapy4

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented. Data are from the product-limit (Kaplan-Meier) method for censored data. (NCT03875092)
Timeframe: Up to approximately 31 months (Database cutoff date of 30-Sep-2020)

InterventionParticipants (Count of Participants)
Pembrolizumab + Chemotherapy65
Chemotherapy60

[back to top]

Incidence of Grade 3-5 Adverse Events

Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The safety and tolerability of durvalumab in combination with chemotherapy in subjects with variant histology bladder cancer who initiate study treatment will be assessed as the number, by treatment cohort, of grade 3, 4, or 5 adverse events, considered probably or definitely related by the investigator. (NCT03912818)
Timeframe: At 120 days

,
Interventionevents (Number)
Grade 3Grade 4Grade 5
Cohort I (Durvalumab, DD MVAC)100
Cohort III (Durvalumab, Carbo-gem)200

[back to top]

Proportion of Subjects Who Initiate Study Treatment and Achieve Tumor Stage of pT2 N0 M0 or Better (e.g., pT0, pT1 N0) at Cystectomy

"Achievement of tumor staging will be determined by pathologist at cystectomy and reported by treatment cohort. Assessed per National Comprehensive Cancer Network bladder cancer guidelines.~T0 N0 M0 = No evidence of primary tumor~T1 N0 M0 = Tumor staging by pathological assessment detected in lamina propria (T0), with no tumor positive nodes (N0).~T2 N0 M0 = Tumor staging by pathological assessment detected in muscularis propria (pT2), with no tumor positive nodes (N0) or tumor metastases (M0) observed." (NCT03912818)
Timeframe: At 20 weeks

InterventionParticipants (Count of Participants)
Cohort I (Durvalumab, DD MVAC)1
Cohort III (Durvalumab, Carbo-gem)1

[back to top]

Adverse Events

All adverse events (AEs) had been determined according to the NCI Common Terminology Criteria for (NCI CTCAE) V5. A summary of the total number of participants is provided. (NCT03913455)
Timeframe: AEs had been recorded from time of signed informed consent until 30 days after discontinuation of study drug(s) or until a new anti-cancer treatment starts, whichever occurs first, up to a maximum of 5 months

InterventionParticipants (Count of Participants)
Guadecitabine and Carboplatin24

[back to top]

Disease Control Rate (DCR)

"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.~DCR defined as CR + PR + Stable Disease (SD) >=8 weeks per RECIST 1.1" (NCT03913455)
Timeframe: Up to a maximum of 7 months

InterventionPercentage of participants (Number)
Guadecitabine and Carboplatin (Platinum Sensitive)42.9
Guadecitabine and Carboplatin (Platinum Resistant)33.3

[back to top]

Overall Survival (OS)

Overall survival is defined as the time from treatment start until death or date of last contact. (NCT03913455)
Timeframe: Time of treatment start until death or date of last contact, up to a maximum of 16 months.

InterventionMonths (Median)
Guadecitabine and Carboplatin (Platinum Sensitive)6.8
Guadecitabine and Carboplatin (Platinum Resistant)4.4

[back to top]

Progression Free Survival (PFS)

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD. PFS is defined as time from registration until disease progression met by RECIST 1.1 or death from any cause. (NCT03913455)
Timeframe: Time of treatment start until the criteria for disease progression or death. Up to a maximum of 7 months.

InterventionMonths (Median)
Guadecitabine and Carboplatin (Platinum Sensitive)1.9
Guadecitabine and Carboplatin (Platinum Resistant)1.7

[back to top]

Objective Response Rate (ORR)

"Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST): Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD) >= 20% increase in tumor burden relative to nadir or the appearance of one or more new lesions; Stable Disease (SD), not meet criteria for CR/PR/PD.~ORR is defined as the proportion of all subjects with confirmed PR or CR according to RECIST 1.1" (NCT03913455)
Timeframe: Up to a maximum of 7 months

InterventionPercentage of participants (Number)
Guadecitabine and Carboplatin (Platinum Sensitive)7.1
Guadecitabine and Carboplatin (Platinum Resistant)0

[back to top]

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as Assessed by Blinded Central Imaging

PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 is presented. (NCT03950674)
Timeframe: Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)

InterventionMonths (Median)
Pembrolizumab16.5
Control7.1

[back to top]

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a study participant administered study drug and which does not necessarily have to have a causal relationship with this study drug. The number of participants who experienced an AE is presented. (NCT03950674)
Timeframe: Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)

InterventionParticipants (Count of Participants)
Pembrolizumab25
Control15

[back to top]

Number of Participants Who Discontinued Any Study Drug Due to an AE

The number of participants who discontinued any randomized study drug due to an AE is presented. (NCT03950674)
Timeframe: Up to approximately 24 months

InterventionParticipants (Count of Participants)
Pembrolizumab9
Control3

[back to top] [back to top]

Overall Survival (OS)

OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS is presented. (NCT03950674)
Timeframe: Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)

InterventionMonths (Median)
PembrolizumabNA
Control25.9

[back to top]

Overall Response Rate (ORR) Per RECIST 1.1 as Assessed by Blinded Central Imaging

ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The percentage of participants who experienced a CR or PR is presented. (NCT03950674)
Timeframe: Through Database Cutoff Date of 20-May-2019 (Up to approximately 31.2 months)

InterventionPercentage of Participants (Number)
Pembrolizumab56.0
Control33.3

[back to top]

Duration of Response (DOR) Per RECIST 1.1 as Assessed by Blinded Central Imaging

For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR was defined as the time from first documented evidence of a CR or PR until PD or death. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. DOR assessments were based on blinded central imaging review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. (NCT03950674)
Timeframe: From time of first documented evidence of CR or PR through database cutoff date of 20-May-2019 (Up to approximately 31.2 months)

InterventionMonths (Median)
Pembrolizumab13.6
Control9.7

[back to top]

Duration of Progression Free Survival (PFS)

Progression free survival (PFS) is defined at the time all participants completed treatment and using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) as >= 20% increase in the sum of target lesions, a measurable increase in a non-target lesion, or the appearance of a new lesion. The duration is measured from the start of treatment to the time of progression or death, whichever occurs first. (NCT03965689)
Timeframe: Up to 2.5 years

Interventionmonths (Median)
Treatment (Paclitaxel, Carboplatin, Pevonedistat)3.68

[back to top]

Overall Survival (OS)

Defined as the duration of time from start of treatment to time of death or last known date alive at the time all participants completed treatment. (NCT03965689)
Timeframe: Up to 2.5 years

Interventionmonths (Median)
Treatment (Paclitaxel, Carboplatin, Pevonedistat)7.73

[back to top]

Objective Response Rate (ORR)

ORR was defined as the proportion of participants with a best overall response of complete response (CR) or partial response (PR) per RECIST v1.1 (as measured by BICR). (NCT04003610)
Timeframe: up to 148 days

Interventionpercentage of participants (Number)
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg0
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg0

[back to top]

EORTC QLQ-C30 Score

The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual. (NCT04003610)
Timeframe: up to 160 days

Interventionscores on a scale (Mean)
Appetite Loss, BaselineAppetite Loss, Cycle 3 Day 1Appetite Loss, Cycle 6 Day 1Appetite Loss, Follow UpCognitive Functioning, BaselineCognitive Functioning, Cycle 3 Day 1Cognitive Functioning, Cycle 6 Day 1Cognitive Functioning, Follow UpConstipation, BaselineConstipation, Cycle 3 Day 1Constipation, Cycle 6 Day 1Constipation, Follow UpDiarrhea, BaselineDiarrhea, Cycle 3 Day 1Diarrhea, Cycle 6 Day 1Diarrhea, Follow UpDyspnea, BaselineDyspnea, Cycle 3 Day 1Dyspnea, Cycle 6 Day 1Dyspnea, Follow UpEmotional Functioning, BaselineEmotional Functioning, Cycle 3 Day 1Emotional Functioning, Cycle 6 Day 1Emotional Functioning, Follow UpFatigue, BaselineFatigue, Cycle 3 Day 1Fatigue, Cycle 6 Day 1Fatigue, Follow UpFinancial Difficulties, BaselineFinancial Difficulties, Cycle 3 Day 1Financial Difficulties, Cycle 6 Day 1Financial Difficulties, Follow UpGlobal Health Status/Quality of Life (QoL), BaselineGlobal Health Status/QoL, Cycle 3 Day 1Global Health Status/QoL, Cycle 6 Day 1Global Health Status/QoL, Follow UpInsomnia, BaselineInsomnia, Cycle 3 Day 1Insomnia, Cycle 6 Day 1Insomnia, Follow UpNausea and Vomiting, BaselineNausea and Vomiting, Cycle 3 Day 1Nausea and Vomiting, Cycle 6 Day 1Nausea and Vomiting, Follow UpPain, BaselinePain, Cycle 3 Day 1Pain, Cycle 6 Day 1Pain, Follow UpPhysical Functioning, BaselinePhysical Functioning, Cycle 3 Day 1Physical Functioning, Cycle 6 Day 1Physical Functioning, Follow UpRole Functioning, BaselineRole Functioning, Cycle 3 Day 1Role Functioning, Cycle 6 Day 1Role Functioning, Follow UpSocial Functioning, BaselineSocial Functioning, Cycle 3 Day 1Social Functioning, Cycle 6 Day 1Social Functioning, Follow Up
Gemcitabine 1000 mg/m^2 Plus carboplatinGemcitabine 1000 mg/m^2 Plus Carboplatin26.716.70.066.766.791.766.783.340.016.70.033.320.00.00.033.326.716.733.366.773.387.591.7100.046.750.033.355.620.016.70.00.051.766.766.750.046.733.30.066.76.78.30.016.740.041.70.016.765.333.366.740.056.733.366.733.353.366.766.783.3

[back to top]

EORTC QLQ-C30 Score

The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual. (NCT04003610)
Timeframe: up to 160 days

Interventionscores on a scale (Mean)
Appetite Loss, BaselineCognitive Functioning, BaselineConstipation, BaselineDiarrhea, BaselineDyspnea, BaselineEmotional Functioning, BaselineFatigue, BaselineFinancial Difficulties, BaselineGlobal Health Status/Quality of Life (QoL), BaselineInsomnia, BaselineNausea and Vomiting, BaselinePain, BaselinePhysical Functioning, BaselineRole Functioning, BaselineSocial Functioning, Baseline
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg33.366.70.00.00.050.044.433.316.733.30.050.073.366.766.7

[back to top]

Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health. (NCT04003610)
Timeframe: Baseline; up to 160 days

Interventionscores on a scale (Mean)
BaselineCycle 4 Day 1Cycle 7 Day 1Follow Up
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg525530

[back to top]

Change From Baseline in the EQ-5D-5L EQ Visual Analog Scale Score

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health. (NCT04003610)
Timeframe: Baseline; up to 160 days

Interventionscores on a scale (Mean)
Baseline
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg40

[back to top]

Change From Baseline in the EORTC QLQ-C30 Score

The European Organization for the Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) contains 30 items and measures 5 functional dimensions (i.e., physical, role, emotional, cognitive, and social), 3 symptom items (i.e., fatigue, nausea/vomiting, and pain), 6 single items (i.e., dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, and financial impact), and a global health and quality of life scale. For each scale and single item, a linear transformation was applied to standardize the scores between 0 (worst) and 100 (best) as described in the EORTC QLQ-C30 Scoring Manual. Change from Baseline was calculated as the post-Baseline value minus the Baseline value. (NCT04003610)
Timeframe: Baseline; up to 160 days

Interventionscores on a scale (Mean)
Appetite Loss, Cycle 3 Day 1Appetite Loss, Cycle 6 Day 1Appetite Loss, Follow UpCognitive Functioning, Cycle 3 Day 1Cognitive Functioning, Cycle 6 Day 1Cognitive Functioning, Follow UpConstipation, Cycle 3 Day 1Constipation, Cycle 6 Day 1Constipation, Follow UpDiarrhea, Cycle 3 Day 1Diarrhea, Cycle 6 Day 1Diarrhea, Follow UpDyspnea, Cycle 3 Day 1Dyspnea, Cycle 6 Day 1Dyspnea, Follow UpEmotional Functioning, Cycle 3 Day 1Emotional Functioning, Cycle 6 Day 1Emotional Functioning, Follow UpFatigue, Cycle 3 Day 1Fatigue, Cycle 6 Day 1Fatigue, Follow UpFinancial Difficulties, Cycle 3 Day 1Financial Difficulties, Cycle 6 Day 1Financial Difficulties, Follow UpGlobal Health Status/QoL, Cycle 3 Day 1Global Health Status/QoL, Cycle 6 Day 1Global Health Status/QoL, Follow UpInsomnia, Cycle 3 Day 1Insomnia, Cycle 6 Day 1Insomnia, Follow UpNausea and Vomiting, Cycle 3 Day 1Nausea and Vomiting, Cycle 6 Day 1Nausea and Vomiting, Follow UpPain, Cycle 3 Day 1Pain, Cycle 6 Day 1Pain, Follow UpPhysical Functioning, Cycle 3 Day 1Physical Functioning, Cycle 6 Day 1Physical Functioning, Follow UpRole Functioning, Cycle 3 Day 1Role Functioning, Cycle 6 Day 1Role Functioning, Follow UpSocial Functioning, Cycle 3 Day 1Social Functioning, Cycle 6 Day 1Social Functioning, Follow Up
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg-16.70.00.033.30.033.3-33.3-33.3-33.3-50.00.0-66.70.033.333.312.50.041.7-11.111.1-44.40.00.0-33.333.316.733.3-16.70.0-33.30.00.00.0-8.30.0-83.3-26.70.0-13.30.00.033.341.733.366.7

[back to top]

Progression-free Survival (PFS)

PFS was defined as the time from the randomization date until the date of disease progression (as measured by a blinded independent central review [BICR] per Response Evaluation Criteria in Solid Tumors version 1.1 [RECIST v1.1]) or death due to any cause, whichever occurred first. (NCT04003610)
Timeframe: up to 130 days

Interventionmonths (Median)
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg1.81
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg2.12

[back to top]

Number of Participants With the Indicated EQ-5D-5L Dimension Scores

The EQ-5D-5L is a standardized instrument for use as a measure of health outcome. The EQ-5D-5L descriptive system is composed of 5 dimensions (mobility, self-case, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 response levels, which are coded by single-digit numbers: 1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = unable to/extreme problems. The EQ-5D-5L also includes a graded (0 [worst overall health] to 100 [best overall health]) vertical visual analog scale that provides a quantitative measure of the participant's perception of their overall health. (NCT04003610)
Timeframe: up to 160 days

InterventionParticipants (Count of Participants)Participants (Count of Participants)
Anxiety/Depression, Baseline72490111Anxiety/Depression, Baseline72490112Anxiety/Depression, Cycle 4 Day 172490112Anxiety/Depression, Cycle 7 Day 172490112Anxiety/Depression, Follow Up72490112Mobility, Baseline72490111Mobility, Baseline72490112Mobility, Cycle 4 Day 172490112Mobility, Cycle 7 Day 172490112Mobility, Follow Up72490112Pain/Discomfort, Baseline72490111Pain/Discomfort, Baseline72490112Pain/Discomfort, Cycle 4 Day 172490112Pain/Discomfort, Cycle 7 Day 172490112Pain/Discomfort, Follow Up72490112Self-care, Baseline72490111Self-care, Baseline72490112Self-care, Cycle 4 Day 172490112Self-care, Cycle 7 Day 172490112Self-care, Follow Up72490112Usual Activities, Baseline72490111Usual Activities, Baseline72490112Usual Activities, Cycle 4 Day 172490112Usual Activities, Cycle 7 Day 172490112Usual Activities, Follow Up72490112
12345
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg3
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg1
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg2
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg0
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg1
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg0

[back to top]

Overall Survival (OS)

OS was defined as the time from the date of randomization until death due to any cause. (NCT04003610)
Timeframe: up to 225 days

Interventionmonths (Median)
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mgNA
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mgNA

[back to top]

Number of Participants With Treatment-emergent Adverse Events

A treatment-emergent adverse event was defined as an adverse event that was either reported for the first time or the worsening of a pre-existing event after the first dose of study drug until 30 days after the last dose of study drug. (NCT04003610)
Timeframe: up to 178 days

InterventionParticipants (Count of Participants)
Pemigatinib 13.5 mg Plus Pembrolizumab 200 mg1
Gemcitabine 1000 mg/m^2 Plus Carboplatin or Pembrolizumab 200 mg6

[back to top]

the Maximum Tolerated Dose (MTD)

The primary endpoint was the MTD of anlotinib, at which less than 33% of patients experienced a DLT in the frst treatment cycle. A DLT involving hematological toxicity was defned as grade 4 and above, non-hematological toxicity as grade 3 and above, and liver and kidney function injury as grade 2 and above. (NCT04012619)
Timeframe: 1 month

Interventionmg (Number)
Anlotinib Hydrochloride Combined With AP10

[back to top]

Percentage of Participants Achieving Mobilization Rate Greater Than or Equal to 2x10^6 CD34+ Cells/kg Body Weight

Percentage of study participants achieving a mobilization rate of greater than or equal to 2x10^6 CD34+ cells/kg body weight. Descriptive statistics will be used to summarize the mobilization rates. (NCT04189952)
Timeframe: 9 weeks

Interventionpercentage of participants (Number)
Acalabrutinib + R-ICENA

[back to top]

Percentage of Participants Achieving Overall Response

Overall response is defined as the percentage of participants who achieved complete response (CR) or partial response (PR) to acalabrutinib + R-ICE therapy. Response will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria. (NCT04189952)
Timeframe: 9 weeks

Interventionpercentage of participants (Number)
Acalabrutinib + R-ICENA

[back to top]

Percentage of Participants Achieving Partial Response (PR)

The percentage of participants achieving partial response (PR) will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria. (NCT04189952)
Timeframe: 9 weeks

Interventionpercentage of participants (Number)
Acalabrutinib + R-ICENA

[back to top]

Number of Treatment-Emergent Adverse Events

The safety profile and tolerability of acalabrutinib + R-ICE will be reported as the number of treatment-emergent adverse events (AEs) or abnormalities of laboratory tests; serious adverse events (SAEs); dose-limiting toxicities (DLTs), or AEs leading to discontinuation of study treatment, or death. Severity and relationship will be assessed by the treating physician using the Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. (NCT04189952)
Timeframe: 13 weeks

InterventionTreatment-emergent adverse events (Number)
Acalabrutinib + R-ICENA

[back to top]

Event-Free Survival (EFS)

Duration of Event-Free Survival (EFS) in study participants. EFS is defined as the time from first dose to documented disease progression, death from any cause, or study dropout, whichever occurs first. (NCT04189952)
Timeframe: Up to 61 weeks

Interventionweeks (Number)
Acalabrutinib + R-ICENA

[back to top]

Progression-Free Survival (PFS)

Duration of Progression-Free Survival (PFS) in study participants. PFS is defined as the time from first dose to documented disease progression, or death from any cause, whichever occurs first. Data for subjects who are still alive and free from progression at the time of data cutoff date, lost to follow-up, or have discontinued the study will be censored on last assessment (or, if no post-baseline tumor assessment, at the time of first dose plus 1 day). (NCT04189952)
Timeframe: Up to 61 weeks

Interventionweeks (Number)
Acalabrutinib + R-ICENA

[back to top]

Overall Survival (OS)

Duration of Overall Survival (OS) in study participants. OS is defined as the time from first dose to death from any cause. Data for subjects who are still alive at the time of data cutoff date, lost to follow-up, have discontinued the study (or, if no post-baseline assessment, at the time of first dose plus 1 day) will be censored. (NCT04189952)
Timeframe: Up to 61 weeks

Interventionweeks (Number)
Acalabrutinib + R-ICENA

[back to top]

Percentage of Participants Achieving Complete Response (CR)

The percentage of participants achieving complete response (CR) will be assessed using Response Evaluation Criteria in Lymphoma (RECIL 2017) criteria. (NCT04189952)
Timeframe: 9 weeks (End of Cycle 3)

Interventionpercentage of participants (Number)
Acalabrutinib + R-ICENA

[back to top]

Number of Participants Experiencing Grade 3 and 4 Adverse Events

Defined by Common Terminology Criteria for Adverse Events version 5.0. Will be summarized by frequency and magnitude. (NCT04631029)
Timeframe: Up to 30 days

InterventionParticipants (Count of Participants)
Grade 3 Adverse EventsGrade 4 Adverse Events
Dose Level 132

[back to top]

Progression Free Survival (PFS) Rate

Defined as the proportion of patients alive and without disease progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Will be estimated with a 90% confidence interval. The Kaplan Meier estimator will be used to estimate survival curves. (NCT04631029)
Timeframe: Up to 2 months

InterventionParticipants (Count of Participants)
Alive without Disease ProgressionDeceased by 2 monthsWithdrew by 2 months
Dose Level 1012

[back to top]

Number of Participants With Dose Limiting Toxicities

The Bayesian optimal interval (BOIN) design will be used to find the MTD based on safety as determined by dose limiting toxicities. (NCT04631029)
Timeframe: Up to 21 days

InterventionParticipants (Count of Participants)
Completed Dose Level 1 without a dose-limiting toxicityExperienced a dose limiting toxicity in Dose Level 1
Dose Level 112

[back to top]

Number of Participants Who Received 3 or More Cycles of the Combination of Entinostat, Atezolizumab, Carboplatin, and Etoposide

The proportion of participants who received 3 or more cycles of the combination, will be calculated with a 90% confidence interval. (NCT04631029)
Timeframe: Up to cycle 4 (1 cycle = 21 days)

InterventionParticipants (Count of Participants)
Received 3 or more cyclesReceived 1 or 2 cycles
Dose Level 103

[back to top]

Run-in Part: Overall Response Rate (ORR) as Per Investigator Assessment

ORR was defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR), as per investigator judgment and according to RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in the SLD of the target lesions or no new lesions or no progression of non-target lesions. (NCT04816214)
Timeframe: Up to end of study, assessed up to 39 weeks

Interventionpercentage of participants (Number)
Run-in Part: Capmatinib + Osimertinib50.0

[back to top]

Run-in Part: Time to Response (TTR) as Per Investigator Assessment

TTR was defined as the duration of time between the date of fist dose of treatmwnr and the date of the first documented response of either CR or PR as per investigator judgment and according to RECIST v1.1 criteria. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions. (NCT04816214)
Timeframe: From first dose of treatment up to end of study, assessed up to 39 weeks

Interventionmonths (Median)
Run-in Part: Capmatinib + OsimertinibNA

[back to top]

Run-in Part: Progression-Free Survival (PFS) as Per Investigator Assessment

PFS was defined as the time (in months) from first dose of treatment to the date of the first documented progression or death due to any cause as per investigator judgment and according to RECIST v1.1. Progression was defined as a ≥20% increase in SLD compared to smallest SLD in the study, or progression of non-target lesions or new lesions. PFS was censored if no PFS event (progression or death) was observed. (NCT04816214)
Timeframe: From first dose of treatment until first documented progression or death or end of study, assessed up to 39 weeks

Interventionmonths (Median)
Run-in Part: Capmatinib + Osimertinib4.58

[back to top]

Run-in Part: Duration of Response (DOR) as Per Investigator Assessment

DOR was defined as the time from first documented response of CR or PR to the date of first documented PD or death due to any cause. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in the SLD of the target lesions or no new lesions or no progression of non-target lesions; PD: ≥20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions. (NCT04816214)
Timeframe: Up to disease progression or death or end of study, assessed up to 39 weeks

Interventionmonths (Median)
Run-in Part: Capmatinib + Osimertinib6.93

[back to top]

Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)

"Blood samples were collected. Tmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.~Actual recorded sampling times were considered for the calculations" (NCT04816214)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

Interventionhours (Median)
Osimertinib: Day 1Osimertinib: Day 15AZ5104: Day 1AZ5104: Day 15AZ7550: Day 1AZ7550: Day 15
Run-in Part: Capmatinib + Osimertinib6.004.0023.14.005.682.25

[back to top]

Run-in Part: Time to Maximum Plasma Concentration (Tmax) of Capmatinib

"Blood samples were collected. Tmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.~Actual recorded sampling times were considered for the calculations" (NCT04816214)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

Interventionhours (Median)
Day 1Day 15
Run-in Part: Capmatinib + Osimertinib1.921.00

[back to top]

Run-in Part: Disease Control Rate (DCR) as Per Investigator Assessment

DCR was defined as the percentage of participants with a BOR of CR, PR, and stable disease (SD) as per investigator judgment and according to RECIST v1.1. Criteria for CR: Disappearance of all lesions and pathologic lymph nodes; PR: ≥30% decrease in SLD of the target lesions or no new lesions or no progression of non-target lesions; SD: Neither sufficient shrinkage to qualify for PR or CR nor and increase in lesions which would qualify for PD. PD: ≥20% increase in SLD compared to the smallest SLD in the study, or progression of non-target lesions or new lesions. (NCT04816214)
Timeframe: From randomization up to end of study, assessed up to 39 weeks

Interventionpercentage of participants (Number)
Run-in Part: Capmatinib + Osimertinib66.7

[back to top]

Run-in Part: Number of Participants With Dose Limiting Toxicities (DLTs)

A DLT was defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to disease, progressive disease, inter-current illness, or concomitant medications, that despite optimal therapeutic intervention that occurred within the first 21 days of treatment with capmatinib in combination with osimertinib. (NCT04816214)
Timeframe: Up to 21 Days

InterventionParticipants (Count of Participants)
Run-in Part: Capmatinib + Osimertinib0

[back to top]

Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)

Blood samples were collected. AUClast of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT04816214)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

Interventionng*hr/mL (Mean)
Osimertinib: Day 1Osimertinib: Day 15AZ5104: Day 1AZ5104: Day 15AZ7550: Day 1AZ7550: Day 15
Run-in Part: Capmatinib + Osimertinib1790138082.913647.1112

[back to top]

Run-in Part: Dose Intensity of Each Study Drug

Dose intensity was computed as the ratio of actual cumulative dose (milligrams) received and actual duration of exposure (weeks) to study drug. (NCT04816214)
Timeframe: From the first dose until last dose of study treatment, assessed up to 39 weeks

Interventionmilligrams per week (mg/week) (Mean)
CapmatinibOsimertinib
Run-in Part: Capmatinib + Osimertinib5042.8534.9

[back to top]

Run-in Part: Maximum Plasma Concentration (Cmax) of Capmatinib

"Blood samples were collected. Cmax of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.~Actual recorded sampling times were considered for the calculations" (NCT04816214)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

Interventionnanograms per milliliter (ng/mL) (Mean)
Day 1Day 15
Run-in Part: Capmatinib + Osimertinib55105750

[back to top]

Run-in Part: Maximum Plasma Concentration (Cmax) of Osimertinib and Its Metabolites (AZ5104 and AZ7550)

Blood samples were collected. Cmax of osimertinib and its metabolites (AZ5104 and AZ7550) was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT04816214)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, 8 and 24 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

Interventionng/mL (Mean)
Osimertinib: Day 1Osimertinib: Day 15AZ5104: Day 1AZ5104: Day 15AZ7550: Day 1AZ7550: Day 15
Run-in Part: Capmatinib + Osimertinib99.52654.8622.03.6133.0

[back to top]

Run-in Part: Median Duration of Exposure to Each Study Drug

Duration of exposure is defined as the time (in weeks) between the first and the last dose of study treatment. (NCT04816214)
Timeframe: From the first dose until last dose of study treatment, assessed up to 39 weeks

Interventionweeks (Median)
CapmatinibOsimertinib
Run-in Part: Capmatinib + Osimertinib23.524.0

[back to top]

Run-in Part: Number of Participants With at Least One Dose Interruption and Dose Reduction of Each Study Drug

Number of participants with at least one dose interruption and dose reduction were reported for each study drug. (NCT04816214)
Timeframe: From the first dose until last dose of study treatment, assessed up to 39 weeks

InterventionParticipants (Count of Participants)
Dose Interruption: CapmatinibDose Interruption: OsimertinibDose Reduction: CapmatinibDose Reduction: Osimertinib
Run-in Part: Capmatinib + Osimertinib5430

[back to top]

Run-in Part: Area Under the Curve to the Last Measurable Concentration (AUClast) of Capmatinib

Blood samples were collected. AUClast of capmatinib was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT04816214)
Timeframe: Pre-dose, 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Days 1 and 15 of Cycle 1 (Cycle = 21 days)

Interventionnanograms*hours/milliliter (ng*hr/mL) (Mean)
Day 1Day 15
Run-in Part: Capmatinib + Osimertinib2010021300

[back to top]

Local Tumor Control

(NCT05718466)
Timeframe: 2 months

InterventionParticipants (Count of Participants)
Fractionated Radiosurgery and Bevacizumab14
Bev With Chemo4

[back to top]

Overall Survival

(NCT05718466)
Timeframe: 12 months

Interventionmonths (Median)
Fractionated Radiosurgery and Bevacizumab7.2
Bev With Chemo4.8

[back to top]

Progression Free Survival

(NCT05718466)
Timeframe: 12 months

Interventionmonths (Median)
Fractionated Radiosurgery and Bevacizumab5.1
Bev With Chemo1.8

[back to top]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
acetylcarnitine
Acetylcarnitine: An acetic acid ester of CARNITINE that facilitates movement of ACETYL COA into the matrices of mammalian MITOCHONDRIA during the oxidation of FATTY ACIDS.		4.1231O-acylcarnitinehuman metabolite
dinitrochlorobenzene
Dinitrochlorobenzene: A skin irritant that may cause dermatitis of both primary and allergic types. Contact sensitization with DNCB has been used as a measure of cellular immunity. DNCB is also used as a reagent for the detection and determination of pyridine compounds.. 1-chloro-2,4-dinitrobenzene : A C-nitro compound that is chlorobenzene carrying a nitro substituent at each of the 2- and 4-positions.		1.9710C-nitro compound;
monochlorobenzenes		allergen;
epitope;
sensitiser
gamma-aminobutyric acid
gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.. gamma-aminobutyric acid : A gamma-amino acid that is butanoic acid with the amino substituent located at C-4.		5.4940amino acid zwitterion;
gamma-amino acid;
monocarboxylic acid		human metabolite;
neurotransmitter;
Saccharomyces cerevisiae metabolite;
signalling molecule
adenine
[no description available]		7.64636-aminopurines;
purine nucleobase		Daphnia magna metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
ammonium hydroxide
azane : Saturated acyclic nitrogen hydrides having the general formula NnHn+2.		5.2731azane;
gas molecular entity;
mononuclear parent hydride		EC 3.5.1.4 (amidase) inhibitor;
metabolite;
mouse metabolite;
neurotoxin;
NMR chemical shift reference compound;
nucleophilic reagent;
refrigerant
quinacrine
Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.. quinacrine : A member of the class of acridines that is acridine substituted by a chloro group at position 6, a methoxy group at position 2 and a [5-(diethylamino)pentan-2-yl]nitrilo group at position 9.		2.1510acridines;
aromatic ether;
organochlorine compound;
tertiary amino compound		antimalarial;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor
beta-alanine
[no description available]		210amino acid zwitterion;
beta-amino acid		agonist;
fundamental metabolite;
human metabolite;
inhibitor;
neurotransmitter
benzene
[no description available]		2.1510aromatic annulene;
benzenes;
volatile organic compound		carcinogenic agent;
environmental contaminant;
non-polar solvent
butyric acid
Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester.. butyrate : A short-chain fatty acid anion that is the conjugate base of butyric acid, obtained by deprotonation of the carboxy group.. butyric acid : A straight-chain saturated fatty acid that is butane in which one of the terminal methyl groups has been oxidised to a carboxy group.		1.9910fatty acid 4:0;
straight-chain saturated fatty acid		human urinary metabolite;
Mycoplasma genitalium metabolite
carbamates
[no description available]		2.4820amino-acid anion
carbamyl phosphate
Carbamyl Phosphate: The monoanhydride of carbamic acid with PHOSPHORIC ACID. It is an important intermediate metabolite and is synthesized enzymatically by CARBAMYL-PHOSPHATE SYNTHASE (AMMONIA) and CARBAMOYL-PHOSPHATE SYNTHASE (GLUTAMINE-HYDROLYZING).		2.1110acyl monophosphate;
one-carbon compound		Escherichia coli metabolite;
mouse metabolite
carbon monoxide
Carbon Monoxide: Carbon monoxide (CO). A poisonous colorless, odorless, tasteless gas. It combines with hemoglobin to form carboxyhemoglobin, which has no oxygen carrying capacity. The resultant oxygen deprivation causes headache, dizziness, decreased pulse and respiratory rates, unconsciousness, and death. (From Merck Index, 11th ed). carbon monoxide : A one-carbon compound in which the carbon is joined only to a single oxygen. It is a colourless, odourless, tasteless, toxic gas.		3.8521carbon oxide;
gas molecular entity;
one-carbon compound		biomarker;
EC 1.9.3.1 (cytochrome c oxidase) inhibitor;
human metabolite;
ligand;
metabolite;
mitochondrial respiratory-chain inhibitor;
mouse metabolite;
neurotoxin;
neurotransmitter;
P450 inhibitor;
probe;
signalling molecule;
vasodilator agent
formic acid
formic acid: RN given refers to parent cpd. formic acid : The simplest carboxylic acid, containing a single carbon. Occurs naturally in various sources including the venom of bee and ant stings, and is a useful organic synthetic reagent. Principally used as a preservative and antibacterial agent in livestock feed. Induces severe metabolic acidosis and ocular injury in human subjects.		1.9910monocarboxylic acidantibacterial agent;
astringent;
metabolite;
protic solvent;
solvent
carnitine
[no description available]		4.5351amino-acid betainehuman metabolite;
mouse metabolite
methane
Methane: The simplest saturated hydrocarbon. It is a colorless, flammable gas, slightly soluble in water. It is one of the chief constituents of natural gas and is formed in the decomposition of organic matter. (Grant & Hackh's Chemical Dictionary, 5th ed). methane : A one-carbon compound in which the carbon is attached by single bonds to four hydrogen atoms. It is a colourless, odourless, non-toxic but flammable gas (b.p. -161degreeC).		5.9771alkane;
gas molecular entity;
mononuclear parent hydride;
one-carbon compound		bacterial metabolite;
fossil fuel;
greenhouse gas
choline
[no description available]		2.4620cholinesallergen;
Daphnia magna metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
neurotransmitter;
nutrient;
plant metabolite;
Saccharomyces cerevisiae metabolite
citric acid, anhydrous
Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability.. citric acid : A tricarboxylic acid that is propane-1,2,3-tricarboxylic acid bearing a hydroxy substituent at position 2. It is an important metabolite in the pathway of all aerobic organisms.		4.9321tricarboxylic acidantimicrobial agent;
chelator;
food acidity regulator;
fundamental metabolite
chlorine
chloride : A halide anion formed when chlorine picks up an electron to form an an anion.		4.4870halide anion;
monoatomic chlorine		cofactor;
Escherichia coli metabolite;
human metabolite
hydrochloric acid
Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. GASTRIC ACID is the hydrochloric acid component of GASTRIC JUICE.. hydrogen chloride : A mononuclear parent hydride consisting of covalently bonded hydrogen and chlorine atoms.		2.110chlorine molecular entity;
gas molecular entity;
hydrogen halide;
mononuclear parent hydride		mouse metabolite
salicylic acid
Scalp: The outer covering of the calvaria. It is composed of several layers: SKIN; subcutaneous connective tissue; the occipitofrontal muscle which includes the tendinous galea aponeurotica; loose connective tissue; and the pericranium (the PERIOSTEUM of the SKULL).		5.8461monohydroxybenzoic acidalgal metabolite;
antifungal agent;
antiinfective agent;
EC 1.11.1.11 (L-ascorbate peroxidase) inhibitor;
keratolytic drug;
plant hormone;
plant metabolite
gallic acid
gallate : A trihydroxybenzoate that is the conjugate base of gallic acid.		7.3110trihydroxybenzoic acidantineoplastic agent;
antioxidant;
apoptosis inducer;
astringent;
cyclooxygenase 2 inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
geroprotector;
human xenobiotic metabolite;
plant metabolite
4-nitrophenylphosphate
nitrophenylphosphate: RN given refers to mono(4-nitrophenyl) ester of phosphoric acid. 4-nitrophenyl phosphate : An aryl phosphate resulting from the mono-esterification of phosphoric acid with 4-nitrophenol.		210aryl phosphatemouse metabolite
malic acid
malic acid : A 2-hydroxydicarboxylic acid that is succinic acid in which one of the hydrogens attached to a carbon is replaced by a hydroxy group.. 2-hydroxydicarboxylic acid : Any dicarboxylic acid carrying a hydroxy group on the carbon atom at position alpha to the carboxy group.		1.99102-hydroxydicarboxylic acid;
C4-dicarboxylic acid		food acidity regulator;
fundamental metabolite
creatine
[no description available]		1.9810glycine derivative;
guanidines;
zwitterion		geroprotector;
human metabolite;
mouse metabolite;
neuroprotective agent;
nutraceutical
cytosine
[no description available]		3.8621aminopyrimidine;
pyrimidine nucleobase;
pyrimidone		Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
lactic acid
Lactic Acid: A normal intermediate in the fermentation (oxidation, metabolism) of sugar. The concentrated form is used internally to prevent gastrointestinal fermentation. (From Stedman, 26th ed). 2-hydroxypropanoic acid : A 2-hydroxy monocarboxylic acid that is propanoic acid in which one of the alpha-hydrogens is replaced by a hydroxy group.		3.49702-hydroxy monocarboxylic acidalgal metabolite;
Daphnia magna metabolite
dimethyl sulfoxide
Dimethyl Sulfoxide: A highly polar organic liquid, that is used widely as a chemical solvent. Because of its ability to penetrate biological membranes, it is used as a vehicle for topical application of pharmaceuticals. It is also used to protect tissue during CRYOPRESERVATION. Dimethyl sulfoxide shows a range of pharmacological activity including analgesia and anti-inflammation.. dimethyl sulfoxide : A 2-carbon sulfoxide in which the sulfur atom has two methyl substituents.		8.3260sulfoxide;
volatile organic compound		alkylating agent;
antidote;
Escherichia coli metabolite;
geroprotector;
MRI contrast agent;
non-narcotic analgesic;
polar aprotic solvent;
radical scavenger
formaldehyde
paraform: polymerized formaldehyde; RN given refers to parent cpd; used in root canal therapy		2.1310aldehyde;
one-carbon compound		allergen;
carcinogenic agent;
disinfectant;
EC 3.5.1.4 (amidase) inhibitor;
environmental contaminant;
Escherichia coli metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
glycine
[no description available]		5.0931alpha-amino acid;
amino acid zwitterion;
proteinogenic amino acid;
serine family amino acid		EC 2.1.2.1 (glycine hydroxymethyltransferase) inhibitor;
fundamental metabolite;
hepatoprotective agent;
micronutrient;
neurotransmitter;
NMDA receptor agonist;
nutraceutical
glycerol
Moon: The natural satellite of the planet Earth. It includes the lunar cycles or phases, the lunar month, lunar landscapes, geography, and soil.		7.0974alditol;
triol		algal metabolite;
detergent;
Escherichia coli metabolite;
geroprotector;
human metabolite;
mouse metabolite;
osmolyte;
Saccharomyces cerevisiae metabolite;
solvent
glycolic acid
glycolic acid: RN given refers to parent cpd. glycolic acid : A 2-hydroxy monocarboxylic acid that is acetic acid where the methyl group has been hydroxylated.		7.6102-hydroxy monocarboxylic acid;
primary alcohol		keratolytic drug;
metabolite
hydrogen carbonate
Bicarbonates: Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.. hydrogencarbonate : The carbon oxoanion resulting from the removal of a proton from carbonic acid.		2.6930carbon oxoanioncofactor;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
dalteparin
Dalteparin: A low-molecular-weight fragment of heparin, prepared by nitrous acid depolymerization of porcine mucosal heparin. The mean molecular weight is 4000-6000 daltons. It is used therapeutically as an antithrombotic agent. (From Merck Index, 11th ed)		5.8122
histamine
[no description available]		10.4241aralkylamino compound;
imidazoles		human metabolite;
mouse metabolite;
neurotransmitter
hydrogen
Hydrogen: The first chemical element in the periodic table with atomic symbol H, and atomic number 1. Protium (atomic weight 1) is by far the most common hydrogen isotope. Hydrogen also exists as the stable isotope DEUTERIUM (atomic weight 2) and the radioactive isotope TRITIUM (atomic weight 3). Hydrogen forms into a diatomic molecule at room temperature and appears as a highly flammable colorless and odorless gas.. dihydrogen : An elemental molecule consisting of two hydrogens joined by a single bond.		4.6111elemental hydrogen;
elemental molecule;
gas molecular entity		antioxidant;
electron donor;
food packaging gas;
fuel;
human metabolite
kynurenine
Kynurenine: A metabolite of the essential amino acid tryptophan metabolized via the tryptophan-kynurenine pathway.. kynurenine : A ketone that is alanine in which one of the methyl hydrogens is substituted by a 2-aminobenzoyl group.		2.0510aromatic ketone;
non-proteinogenic alpha-amino acid;
substituted aniline		human metabolite
thioctic acid
Thioctic Acid: An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS.		2.0210dithiolanes;
heterocyclic fatty acid;
thia fatty acid		fundamental metabolite;
geroprotector
malonic acid
malonic acid : An alpha,omega-dicarboxylic acid in which the two carboxy groups are separated by a single methylene group.. dicarboxylic acid : Any carboxylic acid containing two carboxy groups.		2.1710alpha,omega-dicarboxylic acidhuman metabolite
methanol
Methanol: A colorless, flammable liquid used in the manufacture of FORMALDEHYDE and ACETIC ACID, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness.. primary alcohol : A primary alcohol is a compound in which a hydroxy group, -OH, is attached to a saturated carbon atom which has either three hydrogen atoms attached to it or only one other carbon atom and two hydrogen atoms attached to it.. methanol : The primary alcohol that is the simplest aliphatic alcohol, comprising a methyl and an alcohol group.		2.5320alkyl alcohol;
one-carbon compound;
primary alcohol;
volatile organic compound		amphiprotic solvent;
Escherichia coli metabolite;
fuel;
human metabolite;
mouse metabolite;
Mycoplasma genitalium metabolite
melatonin
[no description available]		8.3811acetamides;
tryptamines		anticonvulsant;
central nervous system depressant;
geroprotector;
hormone;
human metabolite;
immunological adjuvant;
mouse metabolite;
radical scavenger
niacinamide
nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.		13.773225pyridine alkaloid;
pyridinecarboxamide;
vitamin B3		anti-inflammatory agent;
antioxidant;
cofactor;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
Escherichia coli metabolite;
geroprotector;
human urinary metabolite;
metabolite;
mouse metabolite;
neuroprotective agent;
Saccharomyces cerevisiae metabolite;
Sir2 inhibitor
nitrates
Nitrates: Inorganic or organic salts and esters of nitric acid. These compounds contain the NO3- radical.		4.6111monovalent inorganic anion;
nitrogen oxoanion;
reactive nitrogen species
nitric acid
Nitric Acid: Nitric acid (HNO3). A colorless liquid that is used in the manufacture of inorganic and organic nitrates and nitro compounds for fertilizers, dye intermediates, explosives, and many different organic chemicals. Continued exposure to vapor may cause chronic bronchitis; chemical pneumonitis may occur. (From Merck Index, 11th ed). nitric acid : A nitrogen oxoacid of formula HNO3 in which the nitrogen atom is bonded to a hydroxy group and by equivalent bonds to the remaining two oxygen atoms.		2.110nitrogen oxoacidprotic solvent;
reagent
nitrites
Nitrites: Salts of nitrous acid or compounds containing the group NO2-. The inorganic nitrites of the type MNO2 (where M=metal) are all insoluble, except the alkali nitrites. The organic nitrites may be isomeric, but not identical with the corresponding nitro compounds. (Grant & Hackh's Chemical Dictionary, 5th ed)		4.6111monovalent inorganic anion;
nitrogen oxoanion;
reactive nitrogen species		human metabolite
4-aminobenzoic acid
4-Aminobenzoic Acid: An aminobenzoic acid isomer that combines with pteridine and GLUTAMIC ACID to form FOLIC ACID. The fact that 4-aminobenzoic acid absorbs light throughout the UVB range has also resulted in its use as an ingredient in SUNSCREENS.. 4-ammoniobenzoate : A zwitterion obtained by transfer of a proton from the carboxy to the amino group of 4-aminobenzoic acid.. 4-aminobenzoic acid : An aminobenzoic acid in which the amino group is para to the carboxy group.		2.0710aminobenzoic acid;
aromatic amino-acid zwitterion		allergen;
Escherichia coli metabolite;
plant metabolite
propylene glycol
Propylene Glycol: A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations.. propane-1,2-diol : The simplest member of the class of propane-1,2-diols, consisting of propane in which a hydrogen at position 1 and a hydrogen at position 2 are substituted by hydroxy groups. A colourless, viscous, hygroscopic, low-melting (-59degreeC) and high-boiling (188degreeC) liquid with low toxicity, it is used as a solvent, emulsifying agent, and antifreeze.		4.6111glycol;
propane-1,2-diols		allergen;
human xenobiotic metabolite;
mouse metabolite;
protic solvent
pteridines
[no description available]		5.8622azaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
pteridines
pyridine
azine : An organonitrogen compound of general structure RCH=N-N=CHR or RR'C=N-N=CRR'.		2.1710azaarene;
mancude organic heteromonocyclic parent;
monocyclic heteroarene;
pyridines		environmental contaminant;
NMR chemical shift reference compound
pyridoxal phosphate
Pyridoxal Phosphate: This is the active form of VITAMIN B 6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (PYRIDOXAMINE).. pyridoxal 5'-phosphate : The monophosphate ester obtained by condensation of phosphoric acid with the primary hydroxy group of pyridoxal.		2.3110methylpyridines;
monohydroxypyridine;
pyridinecarbaldehyde;
vitamin B6 phosphate		coenzyme;
cofactor;
EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
pyruvic acid
Pyruvic Acid: An intermediate compound in the metabolism of carbohydrates, proteins, and fats. In thiamine deficiency, its oxidation is retarded and it accumulates in the tissues, especially in nervous structures. (From Stedman, 26th ed). pyruvic acid : A 2-oxo monocarboxylic acid that is the 2-keto derivative of propionic acid. It is a metabolite obtained during glycolysis.		2.25102-oxo monocarboxylic acidcofactor;
fundamental metabolite
thiosulfates
Thiosulfates: Inorganic salts of thiosulfuric acid possessing the general formula R2S2O3.. thiosulfate(2-) : A divalent inorganic anion obtained by removal of both protons from thiosulfuric acid.		3.88120divalent inorganic anion;
sulfur oxide;
sulfur oxoanion		human metabolite
selenious acid
Selenious Acid: A selenium compound with the molecular formula H2SO3. It used as a source of SELENIUM, especially for patients that develop selenium deficiency following prolonged PARENTERAL NUTRITION.		4.1831selenium oxoacid
spermine
[no description available]		2.110polyazaalkane;
tetramine		antioxidant;
fundamental metabolite;
immunosuppressive agent
sulfur dioxide
Sulfur Dioxide: A highly toxic, colorless, nonflammable gas. It is used as a pharmaceutical aid and antioxidant. It is also an environmental air pollutant.		4.6111sulfur oxideEscherichia coli metabolite;
food bleaching agent;
refrigerant
taurine
[no description available]		2.4920amino sulfonic acid;
zwitterion		antioxidant;
Escherichia coli metabolite;
glycine receptor agonist;
human metabolite;
mouse metabolite;
nutrient;
radical scavenger;
Saccharomyces cerevisiae metabolite
thiamine
thiamine(1+) : A primary alcohol that is 1,3-thiazol-3-ium substituted by (4-amino-2-methylpyrimidin-5-yl)methyl, methyl and 2-hydroxyethyl groups at positions 3, 4 and 5, respectively.		2.9130primary alcohol;
vitamin B1		Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
thymine
[no description available]		3.3811pyrimidine nucleobase;
pyrimidone		Escherichia coli metabolite;
human metabolite;
mouse metabolite
toluene
methylbenzene : Any alkylbenzene that is benzene substituted with one or more methyl groups.		2.2510methylbenzene;
toluenes;
volatile organic compound		cholinergic antagonist;
fuel additive;
neurotoxin;
non-polar solvent
uracil
2,4-dihydroxypyrimidine: a urinary biomarker for bipolar disorder		10.663312pyrimidine nucleobase;
pyrimidone		allergen;
Daphnia magna metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
prodrug;
Saccharomyces cerevisiae metabolite
uric acid
Uric Acid: An oxidation product, via XANTHINE OXIDASE, of oxypurines such as XANTHINE and HYPOXANTHINE. It is the final oxidation product of purine catabolism in humans and primates, whereas in most other mammals URATE OXIDASE further oxidizes it to ALLANTOIN.. uric acid : An oxopurine that is the final oxidation product of purine metabolism.. 6-hydroxy-1H-purine-2,8(7H,9H)-dione : A tautomer of uric acid having oxo groups at C-2 and C-8 and a hydroxy group at C-6.. 7,9-dihydro-1H-purine-2,6,8(3H)-trione : An oxopurine in which the purine ring is substituted by oxo groups at positions 2, 6, and 8.		2.110uric acidEscherichia coli metabolite;
human metabolite;
mouse metabolite
urea
pseudourea: clinical use; structure. isourea : A carboximidic acid that is the imidic acid tautomer of urea, H2NC(=NH)OH, and its hydrocarbyl derivatives.		5.0352isourea;
monocarboxylic acid amide;
one-carbon compound		Daphnia magna metabolite;
Escherichia coli metabolite;
fertilizer;
flour treatment agent;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
1,2-dimethylhydrazine
1,2-Dimethylhydrazine: A DNA alkylating agent that has been shown to be a potent carcinogen and is widely used to induce colon tumors in experimental animals.. 1,2-dimethylhydrazine : A member of the class of hydrazines that is hydrazine in which one of the hydrogens attached to each nitrogen is replaced by a methyl group. A powerful DNA alkylating agent and carcinogen, it is used to induce colon cancer in laboratory rats and mice.		2.3110hydrazinesalkylating agent;
carcinogenic agent
pk 11195
PK-11195 : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 1-(2-chlorophenyl)isoquinoline-3-carboxylic acid with the amino group of sec-butylmethylamine		2.0810aromatic amide;
isoquinolines;
monocarboxylic acid amide;
monochlorobenzenes		antineoplastic agent
1-anilino-8-naphthalenesulfonate
1-anilino-8-naphthalenesulfonate: RN given refers to parent cpd. 8-anilinonaphthalene-1-sulfonic acid : A naphthalenesulfonic acid that is naphthalene-1-sulfonic acid substituted by a phenylamino group at position 8.		3.8221aminonaphthalene;
naphthalenesulfonic acid		fluorescent probe
2,2'-dipyridyl
2,2'-Dipyridyl: A reagent used for the determination of iron.. 2,2'-bipyridine : A bipyridine in which the two pyridine moieties are linked by a bond between positions C-2 and C-2'.		2.7430bipyridinechelator;
ferroptosis inhibitor
mercaptoethanol
Mercaptoethanol: A water-soluble thiol derived from hydrogen sulfide and ethanol. It is used as a reducing agent for disulfide bonds and to protect sulfhydryl groups from oxidation.		1.9710alkanethiol;
primary alcohol		geroprotector
4-aminopyridine
[no description available]		2.4820aminopyridine;
aromatic amine		avicide;
orphan drug;
potassium channel blocker
phenytoin
[no description available]		9.341imidazolidine-2,4-dioneanticonvulsant;
drug allergen;
sodium channel blocker;
teratogenic agent
hydroxyindoleacetic acid
(5-hydroxyindol-3-yl)acetic acid : A member of the class of indole-3-acetic acids that is indole-3-acetic acid substituted by a hydroxy group at C-5.		2.3920indole-3-acetic acidsdrug metabolite;
human metabolite;
mouse metabolite
acetaminophen
Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak anti-inflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage.. paracetamol : A member of the class of phenols that is 4-aminophenol in which one of the hydrogens attached to the amino group has been replaced by an acetyl group.		2.7630acetamides;
phenols		antipyretic;
cyclooxygenase 1 inhibitor;
cyclooxygenase 2 inhibitor;
cyclooxygenase 3 inhibitor;
environmental contaminant;
ferroptosis inducer;
geroprotector;
hepatotoxic agent;
human blood serum metabolite;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
xenobiotic
acetazolamide
Acetazolamide: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)		2.2510monocarboxylic acid amide;
sulfonamide;
thiadiazoles		anticonvulsant;
diuretic;
EC 4.2.1.1 (carbonic anhydrase) inhibitor
albendazole
[no description available]		2.0610aryl sulfide;
benzimidazoles;
benzimidazolylcarbamate fungicide;
carbamate ester		anthelminthic drug;
microtubule-destabilising agent;
tubulin modulator
alprazolam
Alprazolam: A triazolobenzodiazepine compound with antianxiety and sedative-hypnotic actions, that is efficacious in the treatment of PANIC DISORDERS, with or without AGORAPHOBIA, and in generalized ANXIETY DISORDERS. (From AMA Drug Evaluations Annual, 1994, p238). alprazolam : A member of the class of triazolobenzodiazepines that is 4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepine carrying methyl, phenyl and chloro substituents at positions 1, 6 and 8 respectively. Alprazolam is only found in individuals that have taken this drug.		7.420organochlorine compound;
triazolobenzodiazepine		anticonvulsant;
anxiolytic drug;
GABA agonist;
muscle relaxant;
sedative;
xenobiotic
altretamine
Altretamine: A hexamethyl-2,4,6-triamine derivative of 1,3,5-triazine.		9.26166triamino-1,3,5-triazine
ambroxol
Ambroxol: A metabolite of BROMHEXINE that stimulates mucociliary action and clears the air passages in the respiratory tract. It is usually administered as the hydrochloride.		7.1310aromatic amine
amifostine anhydrous
Amifostine: A phosphorothioate proposed as a radiation-protective agent. It causes splenic vasodilation and may block autonomic ganglia.. amifostine : An organic thiophosphate that is the S-phospho derivative of 2-[(3-aminopropyl)amino]ethanethiol. A prodrug for the free thiol, WR-1065, which is used as a cytoprotectant in cancer chemotherapy and radiotherapy.		16.216743diamine;
organic thiophosphate		antioxidant;
prodrug;
radiation protective agent
p-aminohippuric acid
p-Aminohippuric Acid: The glycine amide of 4-aminobenzoic acid. Its sodium salt is used as a diagnostic aid to measure effective renal plasma flow (ERPF) and excretory capacity.. p-aminohippurate : A hippurate that is the conjugate base of p-aminohippuric acid, arising from deprotonation of the carboxy group.. p-aminohippuric acid : An N-acylglycine that is the 4-amino derivative of hippuric acid; used as a diagnostic agent in the measurement of renal plasma flow.		1.9710N-acylglycineDaphnia magna metabolite
theophylline
[no description available]		6.9810dimethylxanthineadenosine receptor antagonist;
anti-asthmatic drug;
anti-inflammatory agent;
bronchodilator agent;
drug metabolite;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
fungal metabolite;
human blood serum metabolite;
immunomodulator;
muscle relaxant;
vasodilator agent
amsacrine
Amsacrine: An aminoacridine derivative that intercalates into DNA and is used as an antineoplastic agent.. amsacrine : A sulfonamide that is N-phenylmethanesulfonamide substituted by a methoxy group at position 3 and an acridin-9-ylamino group at position 4. It exhibits antineoplastic activity.		4.2730acridines;
aromatic ether;
sulfonamide		antineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor
anastrozole
[no description available]		2.7530nitrile;
triazoles		antineoplastic agent;
EC 1.14.14.14 (aromatase) inhibitor
antipyrine
Antipyrine: An analgesic and antipyretic that has been given by mouth and as ear drops. Antipyrine is often used in testing the effects of other drugs or diseases on drug-metabolizing enzymes in the liver. (From Martindale, The Extra Pharmacopoeia, 30th ed, p29). antipyrine : A pyrazolone derivative that is 1,2-dihydropyrazol-3-one substituted with methyl groups at N-1 and C-5 and with a phenyl group at N-2.		2.0310pyrazoloneantipyretic;
cyclooxygenase 3 inhibitor;
environmental contaminant;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
xenobiotic
azasetron
azasetron: a selective 5-HT3 receptor antagonist; structure given in first source;		9.4522benzoxazine
azathioprine
Azathioprine: An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed). azathioprine : A thiopurine that is 6-mercaptopurine in which the mercapto hydrogen is replaced by a 1-methyl-4-nitroimidazol-5-yl group. It is a prodrug for mercaptopurine and is used as an immunosuppressant, prescribed for the treatment of inflammatory conditions and after organ transplantation and also for treatment of Crohn's didease and MS.		1.9810aryl sulfide;
C-nitro compound;
imidazoles;
thiopurine		antimetabolite;
antineoplastic agent;
carcinogenic agent;
DNA synthesis inhibitor;
hepatotoxic agent;
immunosuppressive agent;
prodrug
benzo(a)pyrene
Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke.. benzo[a]pyrene : An ortho- and peri-fused polycyclic arene consisting of five fused benzene rings.		2.5220ortho- and peri-fused polycyclic arenecarcinogenic agent;
mouse metabolite
benzothiazide
benzothiazide: structure. benzthiazide : 7-Sulfamoyl-1,2,4-benzothiadiazine 1,1-dioxide in which the hydrogen at position 6 is substituted by chlorine and that at position 3 is substituted by a benzylsulfanylmethyl group. A diuretic, it is used to treat hypertension and edema.		4.6111benzothiadiazine;
sulfonamide		antihypertensive agent;
diuretic
berberine
[no description available]		2.3110alkaloid antibiotic;
berberine alkaloid;
botanical anti-fungal agent;
organic heteropentacyclic compound		antilipemic drug;
antineoplastic agent;
antioxidant;
EC 1.1.1.141 [15-hydroxyprostaglandin dehydrogenase (NAD(+))] inhibitor;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
EC 1.13.11.52 (indoleamine 2,3-dioxygenase) inhibitor;
EC 1.21.3.3 (reticuline oxidase) inhibitor;
EC 2.1.1.116 [3'-hydroxy-N-methyl-(S)-coclaurine 4'-O-methyltransferase] inhibitor;
EC 2.1.1.122 [(S)-tetrahydroprotoberberine N-methyltransferase] inhibitor;
EC 2.7.11.10 (IkappaB kinase) inhibitor;
EC 3.1.1.4 (phospholipase A2) inhibitor;
EC 3.1.1.7 (acetylcholinesterase) inhibitor;
EC 3.1.1.8 (cholinesterase) inhibitor;
EC 3.1.3.48 (protein-tyrosine-phosphatase) inhibitor;
EC 3.4.14.5 (dipeptidyl-peptidase IV) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
geroprotector;
hypoglycemic agent;
metabolite;
potassium channel blocker
bicalutamide
bicalutamide: approved for treatment of advanced prostate cancer. N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide : A member of the class of (trifluoromethyl)benzenes that is 4-amino-2-(trifluoromethyl)benzonitrile in which one of the amino hydrogens is substituted by a 3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanoyl group.. bicalutamide : A racemate comprising of equal amounts of (R)-bicalutamide and (S)-bicalutamide. It is an oral non-steroidal antiandrogen used in the treatment of prostate cancer and hirsutism.		2.4720(trifluoromethyl)benzenes;
monocarboxylic acid amide;
monofluorobenzenes;
nitrile;
sulfone;
tertiary alcohol
bisindolylmaleimide i
bisindolylmaleimide I: a bis(indolyl)maleimide		2.0110
bumetanide
[no description available]		210amino acid;
benzoic acids;
sulfonamide		diuretic;
EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor
busulfan
[no description available]		11.71285methanesulfonate esteralkylating agent;
antineoplastic agent;
carcinogenic agent;
insect sterilant;
teratogenic agent
caffeine
[no description available]		4.0731purine alkaloid;
trimethylxanthine		adenosine A2A receptor antagonist;
adenosine receptor antagonist;
adjuvant;
central nervous system stimulant;
diuretic;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
EC 3.1.4.* (phosphoric diester hydrolase) inhibitor;
environmental contaminant;
food additive;
fungal metabolite;
geroprotector;
human blood serum metabolite;
mouse metabolite;
mutagen;
plant metabolite;
psychotropic drug;
ryanodine receptor agonist;
xenobiotic
verapamil
Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.. verapamil : A racemate comprising equimolar amounts of dexverapamil and (S)-verapamil. An L-type calcium channel blocker of the phenylalkylamine class, it is used (particularly as the hydrochloride salt) in the treatment of hypertension, angina pectoris and cardiac arrhythmia, and as a preventive medication for migraine.. 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile : A tertiary amino compound that is 3,4-dimethoxyphenylethylamine in which the hydrogens attached to the nitrogen are replaced by a methyl group and a 4-cyano-4-(3,4-dimethoxyphenyl)-5-methylhexyl group.		8.71100aromatic ether;
nitrile;
polyether;
tertiary amino compound
candesartan cilexetil
candesartan cilexetil: a prodrug which is metabolized to an active form candesartan to exert its biological effects		7.1710biphenyls
carbazilquinone
Carbazilquinone: An alkylating agent structurally similar to MITOMYCIN and found to be effective in the treatment of leukemia and various other neoplasms in mice. It causes leukemia and thrombocytopenia in almost all human patients.		3.3711organic molecular entity
carmustine
Carmustine: A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed). carmustine : A member of the class of N-nitrosoureas that is 1,3-bis(2-chloroethyl)urea in which one of the nitrogens is substituted by a nitroso group.		14.327424N-nitrosoureas;
organochlorine compound		alkylating agent;
antineoplastic agent
celecoxib
[no description available]		11.141611organofluorine compound;
pyrazoles;
sulfonamide;
toluenes		cyclooxygenase 2 inhibitor;
geroprotector;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug
chelerythrine
chelerythrine : A benzophenanthridine alkaloid isolated from the root of Zanthoxylum simulans, Chelidonium majus L., and other Papaveraceae.		2.0210benzophenanthridine alkaloid;
organic cation		antibacterial agent;
antineoplastic agent;
EC 2.7.11.13 (protein kinase C) inhibitor
chlorambucil
Chlorambucil: A nitrogen mustard alkylating agent used as antineoplastic for chronic lymphocytic leukemia, Hodgkin's disease, and others. Although it is less toxic than most other nitrogen mustards, it has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (Merck Index, 11th ed). chlorambucil : A monocarboxylic acid that is butanoic acid substituted at position 4 by a 4-[bis(2-chloroethyl)amino]phenyl group. A chemotherapy drug that can be used in combination with the antibody obinutuzumab for the treatment of chronic lymphocytic leukemia.		4.2941aromatic amine;
monocarboxylic acid;
nitrogen mustard;
organochlorine compound;
tertiary amino compound		alkylating agent;
antineoplastic agent;
carcinogenic agent;
drug allergen;
immunosuppressive agent
chloroquine
Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.. chloroquine : An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis.		7.9840aminoquinoline;
organochlorine compound;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antimalarial;
antirheumatic drug;
autophagy inhibitor;
dermatologic drug
chloroxine
chloroxine : A monohydroxyquinoline that is quinolin-8-ol in which the hydrogens at positions 5 and 7 have been substituted by chlorine. A synthetic antibacterial prepared by chlorination of quinolin-8-ol, it is used for the treatment of dandruff and seborrhoeic dermatitis of the scalp.		2.3110monohydroxyquinoline;
organochlorine compound		antibacterial agent;
antifungal drug;
antiseborrheic
chlorpheniramine
Chlorpheniramine: A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than PROMETHAZINE.. chlorphenamine : A tertiary amino compound that is propylamine which is substituted at position 3 by a pyridin-2-yl group and a p-chlorophenyl group and in which the hydrogens attached to the nitrogen are replaced by methyl groups. A histamine H1 antagonist, it is used to relieve the symptoms of hay fever, rhinitis, urticaria, and asthma.		3.7921monochlorobenzenes;
pyridines;
tertiary amino compound		anti-allergic agent;
antidepressant;
antipruritic drug;
H1-receptor antagonist;
histamine antagonist;
serotonin uptake inhibitor
ci 994
tacedinaline: oral cytostatic drug with impressive differential activity against leukemic cells & normal stem-cells. tacedinaline : A benzamide obtained by formal condensation of the carboxy group of 4-acetamidobenzoic acid with one of the amino groups of 1,2-phenylenediamine. An oral cytostatic drug with impressive differential activity against leukemic cells and normal stem-cells. Also used in combination therapy for selected tumors including non-smoll cell lung, pancreatic, breast, and colorectal cancers.		3.8121acetamides;
benzamides;
substituted aniline		antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
cimetidine
Cimetidine: A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output.. cimetidine : A member of the class of guanidines that consists of guanidine carrying a methyl substituent at position 1, a cyano group at position 2 and a 2-{[(5-methyl-1H-imidazol-4-yl)methyl]sulfanyl}ethyl group at position 3. It is a H2-receptor antagonist that inhibits the production of acid in stomach.		5.262aliphatic sulfide;
guanidines;
imidazoles;
nitrile		adjuvant;
analgesic;
anti-ulcer drug;
H2-receptor antagonist;
P450 inhibitor
ciprofloxacin
Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.. ciprofloxacin : A quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively.		2.3920aminoquinoline;
cyclopropanes;
fluoroquinolone antibiotic;
N-arylpiperazine;
quinolinemonocarboxylic acid;
quinolone antibiotic;
quinolone;
zwitterion		antibacterial drug;
antiinfective agent;
antimicrobial agent;
DNA synthesis inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
environmental contaminant;
topoisomerase IV inhibitor;
xenobiotic
platinum tetrachloride
platinum chloride: RN given refers to cpd with unspecified MF; structure in first source: K2PtCl; see also platinum tetrachloride. platinum dichloride : A platinum coordination entity consisting of platinum(II) bound to two chlorine atoms.		2.4920platinum coordination entitycatalyst;
reagent
cl 387785
CL 387785: structure in first source. N-{4-[(3-bromophenyl)amino]quinazolin-6-yl}but-2-ynamide : A member of the class of quinazolines that is 4,6-diaminoquinazoine in which the one of the hydrogens attached to the amino group at position 4 has been replaced by a m-bromophenyl group while one of the hydrogens attached to the amino group at position 6 has been replaced by a but-2-ynoyl group.		2.0610bromobenzenes;
quinazolines;
secondary carboxamide;
ynamide		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
epidermal growth factor receptor antagonist
clonazepam
Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of GAMMA-AMINOBUTYRIC ACID receptor responses.. clonazepam : 1,3-Dihydro-2H-1,4-benzodiazepin-2-one in which the hydrogens at positions 5 and 7 are substituted by 2-chlorophenyl and nitro groups, respectively. It is used in the treatment of all types of epilepsy and seizures, as well as myoclonus and associated abnormal movements, and panic disorders. However, its use can be limited by the development of tolerance and by sedation.		2.04101,4-benzodiazepinone;
monochlorobenzenes		anticonvulsant;
anxiolytic drug;
GABA modulator
croconazole
croconazole: RN & structure given from first source for parent cpd		3.1710aromatic ether;
conazole antifungal drug;
imidazole antifungal drug;
monochlorobenzenes
deferoxamine
Deferoxamine: Natural product isolated from Streptomyces pilosus. It forms iron complexes and is used as a chelating agent, particularly in the mesylate form.. desferrioxamine B : An acyclic desferrioxamine that is butanedioic acid in which one of the carboxy groups undergoes formal condensation with the primary amino group of N-(5-aminopentyl)-N-hydroxyacetamide and the second carboxy group undergoes formal condensation with the hydroxyamino group of N(1)-(5-aminopentyl)-N(1)-hydroxy-N(4)-[5-(hydroxyamino)pentyl]butanediamide. It is a siderophore native to Streptomyces pilosus biosynthesised by the DesABCD enzyme cluster as a high affinity Fe(III) chelator.		4.8642acyclic desferrioxaminebacterial metabolite;
ferroptosis inhibitor;
iron chelator;
siderophore
eflornithine
Eflornithine: An inhibitor of ORNITHINE DECARBOXYLASE, the rate limiting enzyme of the polyamine biosynthetic pathway.. eflornithine : A fluoroamino acid that is ornithine substituted by a difluoromethyl group at position 2.		4.8721alpha-amino acid;
fluoroamino acid		trypanocidal drug
pentetic acid
Pentetic Acid: An iron chelating agent with properties like EDETIC ACID. DTPA has also been used as a chelator for other metals, such as plutonium.		2.6730pentacarboxylic acidcopper chelator
dimethoate
Dimethoate: An organothiophosphorus cholinesterase inhibitor that is used as a systemic and contact insecticide.. dimethoate : A monocarboxylic acid amide that is N-methylacetamide in which one of the hydrogens of the methyl group attached to the carbonyl moiety is replaced by a (dimethoxyphosphorothioyl)sulfanediyl group.		3.3811monocarboxylic acid amide;
organic thiophosphate		acaricide;
agrochemical;
EC 3.1.1.7 (acetylcholinesterase) inhibitor;
EC 3.1.1.8 (cholinesterase) inhibitor;
environmental contaminant;
insecticide;
xenobiotic
diphenhydramine
Diphenhydramine: A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects.. diphenhydramine : An ether that is the benzhydryl ether of 2-(dimethylamino)ethanol. It is a H1-receptor antagonist used as a antipruritic and antitussive drug.. antitussive : An agent that suppresses cough. Antitussives have a central or a peripheral action on the cough reflex, or a combination of both. Compare with expectorants, which are considered to increase the volume of secretions in the respiratory tract, so facilitating their removal by ciliary action and coughing, and mucolytics, which decrease the viscosity of mucus, facilitating its removal by ciliary action and expectoration.		6.28104ether;
tertiary amino compound		anti-allergic agent;
antidyskinesia agent;
antiemetic;
antiparkinson drug;
antipruritic drug;
antitussive;
H1-receptor antagonist;
local anaesthetic;
muscarinic antagonist;
oneirogen;
sedative
dipyridamole
Dipyridamole: A phosphodiesterase inhibitor that blocks uptake and metabolism of adenosine by erythrocytes and vascular endothelial cells. Dipyridamole also potentiates the antiaggregating action of prostacyclin. (From AMA Drug Evaluations Annual, 1994, p752). dipyridamole : A pyrimidopyrimidine that is 2,2',2'',2'''-(pyrimido[5,4-d]pyrimidine-2,6-diyldinitrilo)tetraethanol substituted by piperidin-1-yl groups at positions 4 and 8 respectively. A vasodilator agent, it inhibits the formation of blood clots.		8.821piperidines;
pyrimidopyrimidine;
tertiary amino compound;
tetrol		adenosine phosphodiesterase inhibitor;
EC 3.5.4.4 (adenosine deaminase) inhibitor;
platelet aggregation inhibitor;
vasodilator agent
valproic acid
Valproic Acid: A fatty acid with anticonvulsant and anti-manic properties that is used in the treatment of EPILEPSY and BIPOLAR DISORDER. The mechanisms of its therapeutic actions are not well understood. It may act by increasing GAMMA-AMINOBUTYRIC ACID levels in the brain or by altering the properties of VOLTAGE-GATED SODIUM CHANNELS.. valproic acid : A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.		5.3541branched-chain fatty acid;
branched-chain saturated fatty acid		anticonvulsant;
antimanic drug;
EC 3.5.1.98 (histone deacetylase) inhibitor;
GABA agent;
neuroprotective agent;
psychotropic drug;
teratogenic agent
domperidone
Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms.. domperidone : 1-[3-(Piperidin-1-yl)propyl]-1,3-dihydro-2H-benzimidazol-2-one in which the 4-position of the piperidine ring is substituted by a 5-chloro-1,3-dihydro-2H-benzimidazol-2-on-1-yl group. A dopamine antagonist, it is used as an antiemetic for the short-term treatment of nausea and vomiting, and to control gastrointestinal effects of dopaminergic drugs given in the management of parkinsonism. The free base is used in oral suspensions, while the maleate salt is used in tablet preparations.		1.9910benzimidazoles;
heteroarylpiperidine		antiemetic;
dopaminergic antagonist
embelin
embelin: from Embelia fruit (Myrsinaceae). embelin : A member of the class of dihydroxy-1,4-benzoquinones that is 2,5-dihydroxy-1,4-benzoquinone which is substituted by an undecyl group at position 3. Isolated from Lysimachia punctata and Embelia ribes, it exhibits antimicrobial, antineoplastic and inhibitory activity towards hepatitis C protease.		2.3110dihydroxy-1,4-benzoquinonesantimicrobial agent;
antineoplastic agent;
hepatitis C protease inhibitor;
plant metabolite
emodin
Emodin: Purgative anthraquinone found in several plants, especially RHAMNUS PURSHIANA. It was formerly used as a laxative, but is now used mainly as a tool in toxicity studies.. emodin : A trihydroxyanthraquinone that is 9,10-anthraquinone which is substituted by hydroxy groups at positions 1, 3, and 8 and by a methyl group at position 6. It is present in the roots and barks of numerous plants (particularly rhubarb and buckthorn), moulds, and lichens. It is an active ingredient of various Chinese herbs.		2.0510trihydroxyanthraquinoneantineoplastic agent;
laxative;
plant metabolite;
tyrosine kinase inhibitor
etanidazole
Etanidazole: A nitroimidazole that sensitizes hypoxic tumor cells that are normally resistant to radiation therapy.. etanidazole : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of (2-nitro-1H-imidazol-1-yl)acetic acid with the amino group of ethanolamine. Used as a radiosensitising agent for hypoxic tumour cells.		5.0352C-nitro compound;
imidazoles;
monocarboxylic acid amide		alkylating agent;
antineoplastic agent;
prodrug;
radiosensitizing agent
ethacrynic acid
Ethacrynic Acid: A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of Henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic.. etacrynic acid : An aromatic ether that is phenoxyacetic acid in which the phenyl ring is substituted by chlorines at positions 2 and 3, and by a 2-methylidenebutanoyl group at position 4. It is a loop diuretic used to treat high blood pressure resulting from diseases such as congestive heart failure, liver failure, and kidney failure. It is also a glutathione S-transferase (EC 2.5.1.18) inhibitor.		210aromatic ether;
aromatic ketone;
dichlorobenzene;
monocarboxylic acid		EC 2.5.1.18 (glutathione transferase) inhibitor;
ion transport inhibitor;
loop diuretic
ethyl loflazepate
ethyl loflazepate: structure given in first source		1.9910organic molecular entity
ethylenediamine
ethylenediamine: RN given refers to parent cpd; edamine is the recommended contraction for the ethylenediamine radical. ethylenediamine : An alkane-alpha,omega-diamine in which the alkane is ethane.		2.4620alkane-alpha,omega-diamineGABA agonist
etodolac
Etodolac: A non-steroidal anti-inflammatory agent and cyclooxygenase-2 (COX-2) inhibitor with potent analgesic and anti-arthritic properties. It has been shown to be effective in the treatment of OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; ANKYLOSING SPONDYLITIS; and in the alleviation of postoperative pain (PAIN, POSTOPERATIVE).. etodolac : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is substituted by a 1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl moiety. A preferential inhibitor of cyclo-oxygenase 2 and non-steroidal anti-inflammatory, it is used for the treatment of rheumatoid arthritis and osteoarthritis, and for the alleviation of postoperative pain. Administered as the racemate, only the (S)-enantiomer is active.		7.0210monocarboxylic acid;
organic heterotricyclic compound		antipyretic;
cyclooxygenase 2 inhibitor;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug
fentanyl
Fentanyl: A potent narcotic analgesic, abuse of which leads to habituation or addiction. It is primarily a mu-opioid agonist. Fentanyl is also used as an adjunct to general anesthetics, and as an anesthetic for induction and maintenance. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1078). fentanyl : A monocarboxylic acid amide resulting from the formal condensation of the aryl amino group of N-phenyl-1-(2-phenylethyl)piperidin-4-amine with propanoic acid.		2.0710anilide;
monocarboxylic acid amide;
piperidines		adjuvant;
anaesthesia adjuvant;
anaesthetic;
intravenous anaesthetic;
mu-opioid receptor agonist;
opioid analgesic
fluconazole
Fluconazole: Triazole antifungal agent that is used to treat oropharyngeal CANDIDIASIS and cryptococcal MENINGITIS in AIDS.. fluconazole : A member of the class of triazoles that is propan-2-ol substituted at position 1 and 3 by 1H-1,2,4-triazol-1-yl groups and at position 2 by a 2,4-difluorophenyl group. It is an antifungal drug used for the treatment of mucosal candidiasis and for systemic infections including systemic candidiasis, coccidioidomycosis, and cryptococcosis.		4.4222conazole antifungal drug;
difluorobenzene;
tertiary alcohol;
triazole antifungal drug		environmental contaminant;
P450 inhibitor;
xenobiotic
flumequine
flumequine: structure. flumequine : A racemate comprising equimolar amounts of R- and S-flumequine. A broad-spectrum antibiotic, formerly used in veterinary medicine for stock breeding and treatment of aquacultures.. 9-fluoro-5-methyl-1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline-2-carboxylic acid : A member of the class of pyridoquinolines that is 1-oxo-6,7-dihydro-1H,5H-pyrido[3,2,1-ij]quinoline carrying additional carboxy, methyl and fluoro substituents at positions 2, 5 and 9 respectively.		2103-oxo monocarboxylic acid;
organofluorine compound;
pyridoquinoline;
quinolone antibiotic
fluorouracil
Fluorouracil: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the THYMIDYLATE SYNTHETASE conversion of deoxyuridylic acid to thymidylic acid.. 5-fluorouracil : A nucleobase analogue that is uracil in which the hydrogen at position 5 is replaced by fluorine. It is an antineoplastic agent which acts as an antimetabolite - following conversion to the active deoxynucleotide, it inhibits DNA synthesis (by blocking the conversion of deoxyuridylic acid to thymidylic acid by the cellular enzyme thymidylate synthetase) and so slows tumour growth.		23.13590192nucleobase analogue;
organofluorine compound		antimetabolite;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
radiosensitizing agent;
xenobiotic
flutamide
Flutamide: An antiandrogen with about the same potency as cyproterone in rodent and canine species.		3.3611(trifluoromethyl)benzenes;
monocarboxylic acid amide		androgen antagonist;
antineoplastic agent
furosemide
Furosemide: A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for EDEMA and chronic RENAL INSUFFICIENCY.. furosemide : A chlorobenzoic acid that is 4-chlorobenzoic acid substituted by a (furan-2-ylmethyl)amino and a sulfamoyl group at position 2 and 5 respectively. It is a diuretic used in the treatment of congestive heart failure.		5.5951chlorobenzoic acid;
furans;
sulfonamide		environmental contaminant;
loop diuretic;
xenobiotic
fusaric acid
Fusaric Acid: A picolinic acid derivative isolated from various Fusarium species. It has been proposed for a variety of therapeutic applications but is primarily used as a research tool. Its mechanisms of action are poorly understood. It probably inhibits DOPAMINE BETA-HYDROXYLASE, the enzyme that converts dopamine to norepinephrine. It may also have other actions, including the inhibition of cell proliferation and DNA synthesis.		7.0310aromatic carboxylic acid;
pyridines
gabapentin
Gabapentin: A cyclohexane-gamma-aminobutyric acid derivative that is used for the treatment of PARTIAL SEIZURES; NEURALGIA; and RESTLESS LEGS SYNDROME.. gabapentin : A gamma-amino acid that is cyclohexane substituted at position 1 by aminomethyl and carboxymethyl groups. Used for treatment of neuropathic pain and restless legs syndrome.		5.0320gamma-amino acidanticonvulsant;
calcium channel blocker;
environmental contaminant;
xenobiotic
gentamicin
Gentamicins: A complex of closely related aminoglycosides obtained from MICROMONOSPORA purpurea and related species. They are broad-spectrum antibiotics, but may cause ear and kidney damage. They act to inhibit PROTEIN BIOSYNTHESIS.		2.4520
glyburide
Glyburide: An antidiabetic sulfonylurea derivative with actions like those of chlorpropamide. glyburide : An N-sulfonylurea that is acetohexamide in which the acetyl group is replaced by a 2-(5-chloro-2-methoxybenzamido)ethyl group.		2.0410monochlorobenzenes;
N-sulfonylurea		anti-arrhythmia drug;
EC 2.7.1.33 (pantothenate kinase) inhibitor;
EC 3.6.3.49 (channel-conductance-controlling ATPase) inhibitor;
hypoglycemic agent
hexamethylene bisacetamide
N,N'-diacetyl-1,6-diaminohexane: chemical name obtained from Acta Biol Hung 1990;41(1-3):199-208		1.9810acetamides
ethidium
Ethidium: A trypanocidal agent and possible antiviral agent that is widely used in experimental cell biology and biochemistry. Ethidium has several experimentally useful properties including binding to nucleic acids, noncompetitive inhibition of nicotinic acetylcholine receptors, and fluorescence among others. It is most commonly used as the bromide.. ethidium : The fluorescent compound widely used in experimental cell biology and biochemistry to reveal double-stranded DNA and RNA.		2.4520phenanthridinesfluorochrome;
intercalator
hydroxychloroquine
Hydroxychloroquine: A chemotherapeutic agent that acts against erythrocytic forms of malarial parasites. Hydroxychloroquine appears to concentrate in food vacuoles of affected protozoa. It inhibits plasmodial heme polymerase. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p970). hydroxychloroquine : An aminoquinoline that is chloroquine in which one of the N-ethyl groups is hydroxylated at position 2. An antimalarial with properties similar to chloroquine that acts against erythrocytic forms of malarial parasites, it is mainly used as the sulfate salt for the treatment of lupus erythematosus, rheumatoid arthritis, and light-sensitive skin eruptions.		2.4110aminoquinoline;
organochlorine compound;
primary alcohol;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antimalarial;
antirheumatic drug;
dermatologic drug
hydroxyurea
[no description available]		15.61164one-carbon compound;
ureas		antimetabolite;
antimitotic;
antineoplastic agent;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
genotoxin;
immunomodulator;
radical scavenger;
teratogenic agent
lidocaine
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.. lidocaine : The monocarboxylic acid amide resulting from the formal condensation of N,N-diethylglycine with 2,6-dimethylaniline.		210benzenes;
monocarboxylic acid amide;
tertiary amino compound		anti-arrhythmia drug;
drug allergen;
environmental contaminant;
local anaesthetic;
xenobiotic
ifosfamide
[no description available]		23.94651271ifosfamidesalkylating agent;
antineoplastic agent;
environmental contaminant;
immunosuppressive agent;
xenobiotic
iodixanol
iodixanol: dimeric contrast media; structure given in first source. iodixanol : A dimeric, non-ionic, water-soluble, radiographic contrast agent, used particularly in coronary angiography.		2.0110organoiodine compoundradioopaque medium
iohexol
Iohexol: An effective non-ionic, water-soluble contrast agent which is used in myelography, arthrography, nephroangiography, arteriography, and other radiographic procedures. Its low systemic toxicity is the combined result of low chemotoxicity and low osmolality.. iohexol : A benzenedicarboxamide compound having N-(2,3-dihydroxypropyl)carbamoyl groups at the 1- and 3-positions, iodo substituents at the 2-, 4- and 6-positions and an N-(2,3-dihydroxypropyl)acetamido group at the 5-position.		7.7730benzenedicarboxamide;
organoiodine compound		environmental contaminant;
radioopaque medium;
xenobiotic
iomeprol
iomeprol: structure given in first source. iomeprol : A benzenedicarboxamide compound having N-substituted carbamoyl groups at the 1- and 3-positions, iodo substituents at the 2-, 4- and 6-positions and a glycoloyl(methyl)amino group at the 5-position.		2.0510benzenedicarboxamide;
organoiodine compound		environmental contaminant;
radioopaque medium;
xenobiotic
isoflurane
Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects.		4.6111organofluorine compoundinhalation anaesthetic
2-propanol
2-Propanol: An isomer of 1-PROPANOL. It is a colorless liquid having disinfectant properties. It is used in the manufacture of acetone and its derivatives and as a solvent. Topically, it is used as an antiseptic.. propan-2-ol : A secondary alcohol that is propane in which one of the hydrogens attached to the central carbon is substituted by a hydroxy group.		2.7830secondary alcohol;
secondary fatty alcohol		protic solvent
ketamine
Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.. ketamine : A member of the class of cyclohexanones in which one of the hydrogens at position 2 is substituted by a 2-chlorophenyl group, while the other is substituted by a methylamino group.		5.231cyclohexanones;
monochlorobenzenes;
secondary amino compound		analgesic;
environmental contaminant;
intravenous anaesthetic;
neurotoxin;
NMDA receptor antagonist;
xenobiotic
ketoconazole
1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.		5.7622dichlorobenzene;
dioxolane;
ether;
imidazoles;
N-acylpiperazine;
N-arylpiperazine
kinetin
Kinetin: A furanyl adenine found in PLANTS and FUNGI. It has plant growth regulation effects.. cytokinin : A phytohormone that promote cell division, or cytokinesis, in plant roots and shoots.. kinetin : A member of the class of 6-aminopurines that is adenine carrying a (furan-2-ylmethyl) substituent at the exocyclic amino group.		2.06106-aminopurines;
furans		cytokinin;
geroprotector
lansoprazole
Lansoprazole: A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers.		2.1310benzimidazoles;
pyridines;
sulfoxide		anti-ulcer drug;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor
leflunomide
Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS.. leflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide.		4.4811(trifluoromethyl)benzenes;
isoxazoles;
monocarboxylic acid amide		antineoplastic agent;
antiparasitic agent;
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
hepatotoxic agent;
immunosuppressive agent;
non-steroidal anti-inflammatory drug;
prodrug;
pyrimidine synthesis inhibitor;
tyrosine kinase inhibitor
letrozole
[no description available]		2.1110nitrile;
triazoles		antineoplastic agent;
EC 1.14.14.14 (aromatase) inhibitor
lg 100268
LG 100268: a retinoid X receptor (RXR) selective compound; structure given in first source		2.1310
lomustine
[no description available]		12.383113N-nitrosoureas;
organochlorine compound		alkylating agent;
antineoplastic agent
lorazepam
Lorazepam: A benzodiazepine used as an anti-anxiety agent with few side effects. It also has hypnotic, anticonvulsant, and considerable sedative properties and has been proposed as a preanesthetic agent.		4.8642benzodiazepine
2-(4-morpholinyl)-8-phenyl-4h-1-benzopyran-4-one
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one: specific inhibitor of phosphatidylinositol 3-kinase; structure in first source		2.7330chromones;
morpholines;
organochlorine compound		autophagy inhibitor;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
geroprotector
mechlorethamine
nitrogen mustard : Compounds having two beta-haloalkyl groups bound to a nitrogen atom, as in (X-CH2-CH2)2NR.		1.9910nitrogen mustard;
organochlorine compound		alkylating agent
memantine
[no description available]		4.6111adamantanes;
primary aliphatic amine		antidepressant;
antiparkinson drug;
dopaminergic agent;
neuroprotective agent;
NMDA receptor antagonist
merbromin
Merbromin: A once-popular mercury containing topical antiseptic.. merbromin : An organic sodium salt that is 2,7-dibromo-4-hydroxymercurifluorescein in which the carboxy group and the phenolic hydroxy group have been deprotonated and the resulting charge is neutralised by two sodium ions.		2.2110
metformin
Metformin: A biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose. (From Martindale, The Extra Pharmacopoeia, 30th ed, p289). metformin : A member of the class of guanidines that is biguanide the carrying two methyl substituents at position 1.		9.31205guanidinesenvironmental contaminant;
geroprotector;
hypoglycemic agent;
xenobiotic
methadone
Methadone: A synthetic opioid that is used as the hydrochloride. It is an opioid analgesic that is primarily a mu-opioid agonist. It has actions and uses similar to those of MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1082-3). methadone : A racemate comprising equimolar amounts of dextromethadone and levomethadone. It is a opioid analgesic which is used as a painkiller and as a substitute for heroin in the treatment of heroin addiction.. 6-(dimethylamino)-4,4-diphenylheptan-3-one : A ketone that is heptan-3-one substituted by a dimethylamino group at position 6 and two phenyl groups at position 4.		5.121benzenes;
diarylmethane;
ketone;
tertiary amino compound
methoxsalen
Methoxsalen: A naturally occurring furocoumarin compound found in several species of plants, including Psoralea corylifolia. It is a photoactive substance that forms DNA ADDUCTS in the presence of ultraviolet A irradiation.. methoxsalen : A member of the class of psoralens that is 7H-furo[3,2-g]chromen-7-one in which the 9 position is substituted by a methoxy group. It is a constituent of the fruits of Ammi majus. Like other psoralens, trioxsalen causes photosensitization of the skin. It is administered topically or orally in conjunction with UV-A for phototherapy treatment of vitiligo and severe psoriasis.		210aromatic ether;
psoralens		antineoplastic agent;
cross-linking reagent;
dermatologic drug;
photosensitizing agent;
plant metabolite
methyl salicylate
methyl salicylate: used in over-the-counter liniments, ointments, lotions for relief of musculoskeletal aches and pains; has hemolytic effect on human & sheep erythrocytes; RN given refers to parent cpd; structure in Merck Index, 9th ed, #5990. methyl salicylate : A benzoate ester that is the methyl ester of salicylic acid.		4.6111benzoate ester;
methyl ester;
salicylates		flavouring agent;
insect attractant;
metabolite
metoclopramide
Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic.. metoclopramide : A member of the class of benzamides resulting from the formal condensation of 4-amino-5-chloro-2-methoxybenzoic acid with the primary amino group of N,N-diethylethane-1,2-diamine.		6.8126benzamides;
monochlorobenzenes;
substituted aniline;
tertiary amino compound		antiemetic;
dopaminergic antagonist;
environmental contaminant;
gastrointestinal drug;
xenobiotic
metronidazole
Metronidazole: A nitroimidazole used to treat AMEBIASIS; VAGINITIS; TRICHOMONAS INFECTIONS; GIARDIASIS; ANAEROBIC BACTERIA; and TREPONEMAL INFECTIONS.. metronidazole : A member of the class of imidazoles substituted at C-1, -2 and -5 with 2-hydroxyethyl, nitro and methyl groups respectively. It has activity against anaerobic bacteria and protozoa, and has a radiosensitising effect on hypoxic tumour cells. It may be given by mouth in tablets, or as the benzoate in an oral suspension. The hydrochloride salt can be used in intravenous infusions. Metronidazole is a prodrug and is selective for anaerobic bacteria due to their ability to intracellularly reduce the nitro group of metronidazole to give nitroso-containing intermediates. These can covalently bind to DNA, disrupting its helical structure, inducing DNA strand breaks and inhibiting bacterial nucleic acid synthesis, ultimately resulting in bacterial cell death.		2.520C-nitro compound;
imidazoles;
primary alcohol		antiamoebic agent;
antibacterial drug;
antimicrobial agent;
antiparasitic agent;
antitrichomonal drug;
environmental contaminant;
prodrug;
radiosensitizing agent;
xenobiotic
midazolam
Midazolam: A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at pH less than 4 and lipid-soluble at physiological pH.. midazolam : An imidazobenzodiazepine that is 4H-imidazo[1,5-a][1,4]benzodiazepine which is substituted by a methyl, 2-fluorophenyl and chloro groups at positions 1, 6 and 8, respectively.		2.0710imidazobenzodiazepine;
monofluorobenzenes;
organochlorine compound		anticonvulsant;
antineoplastic agent;
anxiolytic drug;
apoptosis inducer;
central nervous system depressant;
GABAA receptor agonist;
general anaesthetic;
muscle relaxant;
sedative
mirtazapine
Mirtazapine: A piperazinoazepine tetracyclic compound that enhances the release of NOREPINEPHRINE and SEROTONIN through blockage of presynaptic ALPHA-2 ADRENERGIC RECEPTORS. It also blocks both 5-HT2 and 5-HT3 serotonin receptors and is a potent HISTAMINE H1 RECEPTOR antagonist. It is used for the treatment of depression, and may also be useful for the treatment of anxiety disorders.		2.610benzazepine;
tetracyclic antidepressant		alpha-adrenergic antagonist;
anxiolytic drug;
H1-receptor antagonist;
histamine antagonist;
oneirogen;
serotonergic antagonist
mitotane
Mitotane: A derivative of the insecticide DICHLORODIPHENYLDICHLOROETHANE that specifically inhibits cells of the adrenal cortex and their production of hormones. It is used to treat adrenocortical tumors and causes CNS damage, but no bone marrow depression.		2.930diarylmethane
mitoxantrone
Mitoxantrone: An anthracenedione-derived antineoplastic agent.. mitoxantrone : A dihydroxyanthraquinone that is 1,4-dihydroxy-9,10-anthraquinone which is substituted by 6-hydroxy-1,4-diazahexyl groups at positions 5 and 8.		15.168140dihydroxyanthraquinoneanalgesic;
antineoplastic agent
entinostat
[no description available]		8.9911benzamides;
carbamate ester;
primary amino compound;
pyridines;
substituted aniline		antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
deet
N,N-diethyl-m-toluamide : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of m-toluic acid with the nitrogen of diethylamine. First developed by the U.S. Army in 1946 for use by military personnel in insect-infested areas, it is the most widely used insect repellent worldwide.		2.610benzamides;
monocarboxylic acid amide		environmental contaminant;
insect repellent;
xenobiotic
nalidixic acid
[no description available]		2101,8-naphthyridine derivative;
monocarboxylic acid;
quinolone antibiotic		antibacterial drug;
antimicrobial agent;
DNA synthesis inhibitor
activins
Activins: Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.		2.1710
nicardipine
Nicardipine: A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents.. nicardipine : A racemate comprising equimolar amounts of (R)- and (S)-nicardipine. It is a calcium channel blocker which is used to treat hypertension.. 2-[benzyl(methyl)amino]ethyl methyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate : A dihydropyridine that is 1,4-dihydropyridine substituted by a methyl, {2-[benzyl(methyl)amino]ethoxy}carbonyl, 3-nitrophenyl, methoxycarbonyl and methyl groups at positions 2, 3, 4, 5 and 6, respectively.		2.1110benzenes;
C-nitro compound;
diester;
dihydropyridine;
methyl ester;
tertiary amino compound
niclosamide
Niclosamide: An antihelmintic that is active against most tapeworms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p48). niclosamide : A secondary carboxamide resulting from the formal condensation of the carboxy group of 5-chlorosalicylic acid with the amino group of 2-chloro-4-nitroaniline. It is an oral anthelmintic drug approved for use against tapeworm infections.		2.5120benzamides;
C-nitro compound;
monochlorobenzenes;
salicylanilides;
secondary carboxamide		anthelminthic drug;
anticoronaviral agent;
antiparasitic agent;
apoptosis inducer;
molluscicide;
piscicide;
STAT3 inhibitor
nifedipine
Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure.		1.9810C-nitro compound;
dihydropyridine;
methyl ester		calcium channel blocker;
human metabolite;
tocolytic agent;
vasodilator agent
nitroglycerin
Nitroglycerin: A volatile vasodilator which relieves ANGINA PECTORIS by stimulating GUANYLATE CYCLASE and lowering cytosolic calcium. It is also sometimes used for TOCOLYSIS and explosives.. nitroglycerol : A nitrate ester that is glycerol in which nitro group(s) replace the hydrogen(s) attached to one or more of the hydroxy groups.. nitroglycerin : A nitroglycerol that is glycerol in which the hydrogen atoms of all three hydroxy groups are replaced by nitro groups. It acts as a prodrug, releasing nitric oxide to open blood vessels and so alleviate heart pain.		6.9744nitroglycerolexplosive;
muscle relaxant;
nitric oxide donor;
prodrug;
tocolytic agent;
vasodilator agent;
xenobiotic
5-nitro-2-(3-phenylpropylamino)benzoic acid
5-nitro-2-(3-phenylpropylamino)benzoic acid: structure given in first source; chloride channel antagonist		2.0510nitrobenzoic acid
ns 1619
NS 1619: structure given in first source. NS 1619 : A member of the class of benzimidazoles that is 1,3-dihydro-2H-benzimidazol-2-one in which the hydrogens at positions 1 and 5 are replaced are replaced by 2-hydroxy-5-(trifluoromethyl)phenyl and trifluoromethyl groups, respectively. It is an opener/activator of the large-conductance calcium-activated potassium channel (Bkca).		2.0110(trifluoromethyl)benzenes;
benzimidazoles;
phenols		potassium channel opener
n-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide: structure given in first source. NS-398 : A C-nitro compound that is N-methylsulfonyl-4-nitroaniline bearing an additional cyclohexyloxy substituent at position 2.		2.0310aromatic ether;
C-nitro compound;
sulfonamide		antineoplastic agent;
cyclooxygenase 2 inhibitor
o(6)-benzylguanine
O(6)-benzylguanine: a suicide inhibitor of O(6)-methylguanine-DNA methyltransferase activity		2.4320
ofloxacin
Ofloxacin: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.. 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid : An oxazinoquinoline that is 2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinolin-7-one substituted by methyl, carboxy, fluoro, and 4-methylpiperazin-1-yl groups at positions 3, 6, 9, and 10, respectively.. ofloxacin : A racemate comprising equimolar amounts of levofloxacin and dextrofloxacin. It is a synthetic fluoroquinolone antibacterial agent which inhibits the supercoiling activity of bacterial DNA gyrase, halting DNA replication.		8.82213-oxo monocarboxylic acid;
N-arylpiperazine;
N-methylpiperazine;
organofluorine compound;
oxazinoquinoline
ondansetron
Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and has reported anxiolytic and neuroleptic properties.		10.643121carbazoles
oxonic acid
Oxonic Acid: Antagonist of urate oxidase.		11.7241191,3,5-triazines;
monocarboxylic acid
1,2-cyclohexanediamine
1,2-cyclohexanediamine: RN given refers to cpd without isomeric designation		2.3920primary aliphatic amine
oxolinic acid
quinolone antibiotic : An organonitrogen heterocyclic antibiotic whose structure contains a quinolone or quinolone-related skeleton.		210aromatic carboxylic acid;
organic heterotricyclic compound;
oxacycle;
quinolinemonocarboxylic acid;
quinolone antibiotic		antibacterial drug;
antifungal agent;
antiinfective agent;
antimicrobial agent;
enzyme inhibitor
pamidronate
[no description available]		9.6861phosphonoacetic acid
pentamidine
Pentamidine: Antiprotozoal agent effective in trypanosomiasis, leishmaniasis, and some fungal infections; used in treatment of PNEUMOCYSTIS pneumonia in HIV-infected patients. It may cause diabetes mellitus, central nervous system damage, and other toxic effects.. pentamidine : A diether consisting of pentane-1,5-diol in which both hydroxyl hydrogens have been replaced by 4-amidinophenyl groups. A trypanocidal drug that is used for treatment of cutaneous leishmaniasis and Chagas disease.		1.9710aromatic ether;
carboxamidine;
diether		anti-inflammatory agent;
antifungal agent;
calmodulin antagonist;
chemokine receptor 5 antagonist;
EC 2.3.1.48 (histone acetyltransferase) inhibitor;
NMDA receptor antagonist;
S100 calcium-binding protein B inhibitor;
trypanocidal drug;
xenobiotic
pentoxifylline
[no description available]		7.110oxopurine
phenobarbital
Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.. phenobarbital : A member of the class of barbiturates, the structure of which is that of barbituric acid substituted at C-5 by ethyl and phenyl groups.		2.0110barbituratesanticonvulsant;
drug allergen;
excitatory amino acid antagonist;
sedative
4-phenylbutyric acid
4-phenylbutyric acid: RN refers to the parent cpd. 4-phenylbutyric acid : A monocarboxylic acid the structure of which is that of butyric acid substituted with a phenyl group at C-4. It is a histone deacetylase inhibitor that displays anticancer activity. It inhibits cell proliferation, invasion and migration and induces apoptosis in glioma cells. It also inhibits protein isoprenylation, depletes plasma glutamine, increases production of foetal haemoglobin through transcriptional activation of the gamma-globin gene and affects hPPARgamma activation.		7.1510monocarboxylic acidantineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor;
prodrug
pifithrin
pifithrin: a tetrahydrobenzothiazol; inhibitor of P53 that protects mice from the side effects of cancer therapy; structure in first source		2.2510aromatic ketone
potassium chloride
Potassium Chloride: A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA.. potassium chloride : A metal chloride salt with a K(+) counterion.		1.9910inorganic chloride;
inorganic potassium salt;
potassium salt		fertilizer
4-aminobenzoic acid
para-Aminobenzoates: Benzoic acids, salts, or esters that contain an amino group attached to carbon number 4 of the benzene ring structure.. 4-aminobenzoate : An aromatic amino-acid anion that is the conjugate base of 4-aminobenzoic acid.		2.0710aminobenzoate;
aromatic amino-acid anion		Escherichia coli metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
prazosin
Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of HEART FAILURE; HYPERTENSION; PHEOCHROMOCYTOMA; RAYNAUD DISEASE; PROSTATIC HYPERTROPHY; and URINARY RETENTION.. prazosin : A member of the class of piperazines that is piperazine substituted by a furan-2-ylcarbonyl group and a 4-amino-6,7-dimethoxyquinazolin-2-yl group at positions 1 and 4 respectively.		1.9910aromatic ether;
furans;
monocarboxylic acid amide;
piperazines;
quinazolines		alpha-adrenergic antagonist;
antihypertensive agent;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor
procaine
Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016).. procaine : A benzoate ester, formally the result of esterification of 4-aminobenzoic acid with 2-diethylaminoethanol but formed experimentally by reaction of ethyl 4-aminobenzoate with 2-diethylaminoethanol.		2.0110benzoate ester;
substituted aniline;
tertiary amino compound		central nervous system depressant;
drug allergen;
local anaesthetic;
peripheral nervous system drug
procarbazine
Procarbazine: An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease.. procarbazine : A benzamide obtained by formal condensation of the carboxy group of 4-[(2-methylhydrazino)methyl]benzoic acid with the amino group of isopropylamine. An antineoplastic chemotherapy drug used for treatment of Hodgkin's lymphoma. Metabolism yields azo-procarbazine and hydrogen peroxide, which results in the breaking of DNA strands.		17.33016benzamides;
hydrazines		antineoplastic agent
prochlorperazine
Prochlorperazine: A phenothiazine antipsychotic used principally in the treatment of NAUSEA; VOMITING; and VERTIGO. It is more likely than CHLORPROMAZINE to cause EXTRAPYRAMIDAL DISORDERS. (From Martindale, The Extra Pharmacopoeia, 30th ed, p612). prochlorperazine : A member of the class of phenothiazines that is 10H-phenothiazine having a chloro substituent at the 2-position and a 3-(4-methylpiperazin-1-yl)propyl group at the N-10 position.		10.8464N-alkylpiperazine;
N-methylpiperazine;
organochlorine compound;
phenothiazines		alpha-adrenergic antagonist;
antiemetic;
cholinergic antagonist;
dopamine receptor D2 antagonist;
dopaminergic antagonist;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
first generation antipsychotic
propantheline
Propantheline: A muscarinic antagonist used as an antispasmodic, in rhinitis, in urinary incontinence, and in the treatment of ulcers. At high doses it has nicotinic effects resulting in neuromuscular blocking.		8.3811xanthenes
propidium
Propidium: Quaternary ammonium analog of ethidium; an intercalating dye with a specific affinity to certain forms of DNA and, used as diiodide, to separate them in density gradients; also forms fluorescent complexes with cholinesterase which it inhibits.		2.110phenanthridines;
quaternary ammonium ion		fluorochrome;
intercalator
propranolol
Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.. propranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3.		3.5911naphthalenes;
propanolamine;
secondary amine		anti-arrhythmia drug;
antihypertensive agent;
anxiolytic drug;
beta-adrenergic antagonist;
environmental contaminant;
human blood serum metabolite;
vasodilator agent;
xenobiotic
protoporphyrin ix
protoporphyrin IX: RN given refers to parent cpd; structure in Merck Index, 9th ed, #7685. protoporphyrin : A cyclic tetrapyrrole that consists of porphyrin bearing four methyl substituents at positions 3, 8, 13 and 17, two vinyl substituents at positions 7 and 12 and two 2-carboxyethyl substituents at positions 2 and 18. The parent of the class of protoporphyrins.		2.1310
semustine
Semustine: 4-Methyl derivative of LOMUSTINE; (CCNU). An antineoplastic agent which functions as an alkylating agent.. semustine : An organochlorine compound that is urea in which the two hydrogens on one of the amino groups are replaced by nitroso and 2-chloroethyl groups and one hydrogen from the other amino group is replaced by a 4-methylcyclohexyl group.		3.0910N-nitrosoureas;
organochlorine compound		alkylating agent;
antineoplastic agent;
carcinogenic agent
sodium fluoride
[no description available]		6.9810fluoride saltmutagen
sodium iodide
Sodium Iodide: A compound forming white, odorless deliquescent crystals and used as iodine supplement, expectorant or in its radioactive (I-131) form as an diagnostic aid, particularly for thyroid function tests.. sodium iodide : A metal iodide salt with a Na(+) counterion.		7.110inorganic sodium salt;
iodide salt
streptonigrin
[no description available]		2.0810pyridines;
quinolone		antimicrobial agent;
antineoplastic agent
vorinostat
Vorinostat: A hydroxamic acid and anilide derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used in the treatment of CUTANEOUS T-CELL LYMPHOMA and SEZARY SYNDROME.. vorinostat : A dicarboxylic acid diamide comprising suberic (octanedioic) acid coupled to aniline and hydroxylamine. A histone deacetylase inhibitor, it is marketed under the name Zolinza for the treatment of cutaneous T cell lymphoma (CTCL).		7.94105dicarboxylic acid diamide;
hydroxamic acid		antineoplastic agent;
apoptosis inducer;
EC 3.5.1.98 (histone deacetylase) inhibitor
sulforaphane
sulforaphane: from Cardaria draba L.. sulforaphane : An isothiocyanate having a 4-(methylsulfinyl)butyl group attached to the nitrogen.		2.1310isothiocyanate;
sulfoxide		antineoplastic agent;
antioxidant;
EC 3.5.1.98 (histone deacetylase) inhibitor;
plant metabolite
suramin
Suramin: A polyanionic compound with an unknown mechanism of action. It is used parenterally in the treatment of African trypanosomiasis and it has been used clinically with diethylcarbamazine to kill the adult Onchocerca. (From AMA Drug Evaluations Annual, 1992, p1643) It has also been shown to have potent antineoplastic properties.. suramin : A member of the class of phenylureas that is urea in which each of the amino groups has been substituted by a 3-({2-methyl-5-[(4,6,8-trisulfo-1-naphthyl)carbamoyl]phenyl}carbamoyl)phenyl group. An activator of both the rabbit skeletal muscle RyR1 and sheep cardiac RyR2 isoform ryanodine receptor channels, it has been used for the treatment of human African trypanosomiasis for over 100 years.		6.7973naphthalenesulfonic acid;
phenylureas;
secondary carboxamide		angiogenesis inhibitor;
antinematodal drug;
antineoplastic agent;
apoptosis inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
GABA antagonist;
GABA-gated chloride channel antagonist;
purinergic receptor P2 antagonist;
ryanodine receptor agonist;
trypanocidal drug
tegafur
[no description available]		13.97936organohalogen compound;
pyrimidines
temozolomide
[no description available]		14.185112imidazotetrazine;
monocarboxylic acid amide;
triazene derivative		alkylating agent;
antineoplastic agent;
prodrug
thalidomide
Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.		12.872414phthalimides;
piperidones
thioridazine
Thioridazine: A phenothiazine antipsychotic used in the management of PHYCOSES, including SCHIZOPHRENIA.. thioridazine : A phenothiazine derivative having a methylsulfanyl subsitituent at the 2-position and a (1-methylpiperidin-2-yl)ethyl] group at the N-10 position.		7.1510phenothiazines;
piperidines		alpha-adrenergic antagonist;
dopaminergic antagonist;
EC 1.8.1.12 (trypanothione-disulfide reductase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
first generation antipsychotic;
H1-receptor antagonist;
serotonergic antagonist
thiotepa
Thiotepa: A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed).		18.7921297aziridines
tolbutamide
Tolbutamide: A sulphonylurea hypoglycemic agent with actions and uses similar to those of CHLORPROPAMIDE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p290). tolbutamide : An N-sulfonylurea that consists of 1-butylurea having a tosyl group attached at the 3-position.		2.0410N-sulfonylureahuman metabolite;
hypoglycemic agent;
insulin secretagogue;
potassium channel blocker
trientine
Trientine: An ethylenediamine derivative used as stabilizer for EPOXY RESINS, as ampholyte for ISOELECTRIC FOCUSING and as chelating agent for copper in HEPATOLENTICULAR DEGENERATION.. TETA : An azamacrocyle in which four nitrogen atoms at positions 1, 4, 8 and 11 of a fouteen-membered ring are each substituted with a carboxymethyl group.. 2,2,2-tetramine : A polyazaalkane that is decane in which the carbon atoms at positions 1, 4, 7 and 10 are replaced by nitrogens.		10.6232polyazaalkane;
tetramine		copper chelator
trimetrexate
Trimetrexate: A nonclassical folic acid inhibitor through its inhibition of the enzyme dihydrofolate reductase. It is being tested for efficacy as an antineoplastic agent and as an antiparasitic agent against PNEUMOCYSTIS PNEUMONIA in AIDS patients. Myelosuppression is its dose-limiting toxic effect.		3.3811
talactoferrin alfa
talactoferrin alfa: recombinant human lactoferrin, an oral drug for treatment of refractory solid tumors; in Phase I trial 5/2006		4.9621acetamides
urethane
[no description available]		2.4110carbamate esterfungal metabolite;
mutagen
xylazine
Xylazine: An adrenergic alpha-2 agonist used as a sedative, analgesic and centrally acting muscle relaxant in VETERINARY MEDICINE.. xylazine : A methyl benzene that is 1,3-dimethylbenzene which is substituted by a 5,6-dihydro-4H-1,3-thiazin-2-ylnitrilo group at position 2. It is an alpha2 adrenergic receptor agonist and frequently used in veterinary medicine as an emetic and sedative with analgesic and muscle relaxant properties.		1.98101,3-thiazine;
methylbenzene;
secondary amino compound		alpha-adrenergic agonist;
analgesic;
emetic;
muscle relaxant;
sedative
zinc chloride
zinc chloride: RN given refers to parent cpd. zinc dichloride : A compound of zinc and chloride ions in the ratio 1:2. It exists in four crystalline forms, in each of which the Zn(2+) ions are trigonal planar coordinated to four chloride ions.		2.0110inorganic chloride;
zinc molecular entity		astringent;
disinfectant;
EC 5.3.3.5 (cholestenol Delta-isomerase) inhibitor;
Lewis acid
mitomycin
Mitomycin: An antineoplastic antibiotic produced by Streptomyces caespitosus. It is one of the bi- or tri-functional ALKYLATING AGENTS causing cross-linking of DNA and inhibition of DNA synthesis.. mitomycin : A family of aziridine-containing natural products isolated from Streptomyces caespitosus or Streptomyces lavendulae.		15.1611126mitomycinalkylating agent;
antineoplastic agent
prednisolone
Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states.. prednisolone : A glucocorticoid that is prednisone in which the oxo group at position 11 has been reduced to the corresponding beta-hydroxy group. It is a drug metabolite of prednisone.		11.7533511beta-hydroxy steroid;
17alpha-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(1),Delta(4)-steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		adrenergic agent;
anti-inflammatory drug;
antineoplastic agent;
drug metabolite;
environmental contaminant;
immunosuppressive agent;
xenobiotic
estriol
hormonin: estrogen replacement; each tablet contains 600 ug micronized 17beta-estradiol, 270 ug estriol and 1.4 mg estrone. chlorapatite : A phosphate mineral with the formula Ca5(PO4)3Cl.		2.061016alpha-hydroxy steroid;
17beta-hydroxy steroid;
3-hydroxy steroid		estrogen;
human metabolite;
human xenobiotic metabolite;
mouse metabolite
cephaloridine
Cephaloridine: A cephalosporin antibiotic.. cefaloridine : A cephalosporin compound having pyridinium-1-ylmethyl and 2-thienylacetamido side-groups. A first-generation semisynthetic derivative of cephalosporin C.		2.0410beta-lactam antibiotic allergen;
cephalosporin;
semisynthetic derivative		antibacterial drug
thymidine
[no description available]		6.07113pyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
metabolite;
mouse metabolite
floxuridine
Floxuridine: An antineoplastic antimetabolite that is metabolized to fluorouracil when administered by rapid injection; when administered by slow, continuous, intra-arterial infusion, it is converted to floxuridine monophosphate. It has been used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.. floxuridine : A pyrimidine 2'-deoxyribonucleoside compound having 5-fluorouracil as the nucleobase; used to treat hepatic metastases of gastrointestinal adenocarcinomas and for palliation in malignant neoplasms of the liver and gastrointestinal tract.		14.4155nucleoside analogue;
organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
radiosensitizing agent
benzimidazole
1H-benzimidazole : The 1H-tautomer of benzimidazole.		2.0510benzimidazole;
polycyclic heteroarene
bromouracil
Bromouracil: 5-Bromo-2,4(1H,3H)-pyrimidinedione. Brominated derivative of uracil that acts as an antimetabolite, substituting for thymine in DNA. It is used mainly as an experimental mutagen, but its deoxyriboside (BROMODEOXYURIDINE) is used to treat neoplasms.. 5-bromouracil : A pyrimidine having keto groups at the 2- and 4-positions and a bromo group at the 5-position. Used mainly as an experimental mutagen.		3.3110nucleobase analogue;
pyrimidines		mutagen
thyroxine
Thyroxine: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.. thyroxine : An iodothyronine compound having iodo substituents at the 3-, 3'-, 5- and 5'-positions.		4.93212-halophenol;
iodophenol;
L-phenylalanine derivative;
non-proteinogenic L-alpha-amino acid;
thyroxine zwitterion;
thyroxine		antithyroid drug;
human metabolite;
mouse metabolite;
thyroid hormone
carbachol
Carbachol: A slowly hydrolyzed CHOLINERGIC AGONIST that acts at both MUSCARINIC RECEPTORS and NICOTINIC RECEPTORS.		1.9910ammonium salt;
carbamate ester		cardiotonic drug;
miotic;
muscarinic agonist;
nicotinic acetylcholine receptor agonist;
non-narcotic analgesic
penicillamine
Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease.. penicillamine : An alpha-amino acid having the structure of valine substituted at the beta position with a sulfanyl group.		7.1510non-proteinogenic alpha-amino acid;
penicillamine		antirheumatic drug;
chelator;
copper chelator;
drug allergen
prednisone
Prednisone: A synthetic anti-inflammatory glucocorticoid derived from CORTISONE. It is biologically inert and converted to PREDNISOLONE in the liver.. prednisone : A synthetic glucocorticoid drug that is particularly effective as an immunosuppressant, and affects virtually all of the immune system. Prednisone is a prodrug that is converted by the liver into prednisolone (a beta-hydroxy group instead of the oxo group at position 11), which is the active drug and also a steroid.		12.16441111-oxo steroid;
17alpha-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(1),Delta(4)-steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		adrenergic agent;
anti-inflammatory drug;
antineoplastic agent;
immunosuppressive agent;
prodrug
estrone
Hydroxyestrones: Estrone derivatives substituted with one or more hydroxyl groups in any position. They are important metabolites of estrone and other estrogens.		7.411017-oxo steroid;
3-hydroxy steroid;
phenolic steroid;
phenols		antineoplastic agent;
bone density conservation agent;
estrogen;
human metabolite;
mouse metabolite
amifampridine
Amifampridine: 4-Aminopyridine derivative that acts as a POTASSIUM CHANNEL blocker to increase release of ACETYLCHOLINE from nerve terminals. It is used in the treatment of CONGENITAL MYASTHENIC SYNDROMES.		2.0310aminopyridine
triiodothyronine
Triiodothyronine: A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5' position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly T3.. 3,3',5-triiodo-L-thyronine : An iodothyronine compound having iodo substituents at the 3-, 3'- and 5-positions. Although some is produced in the thyroid, most of the 3,3',5-triiodo-L-thyronine in the body is generated by mono-deiodination of L-thyroxine in the peripheral tissues. Its metabolic activity is about 3 to 5 times that of L-thyroxine. The sodium salt is used in the treatment of hypothyroidism.		3.18102-halophenol;
amino acid zwitterion;
iodophenol;
iodothyronine		human metabolite;
mouse metabolite;
thyroid hormone
cantharidin
Cantharidin: A toxic compound, isolated from the Spanish fly or blistering beetle (Lytta (Cantharis) vesicatoria) and other insects. It is a potent and specific inhibitor of protein phosphatases 1 (PP1) and 2A (PP2A). This compound can produce severe skin inflammation, and is extremely toxic if ingested orally.. cantharidin : A monoterpenoid with an epoxy-bridged cyclic dicarboxylic anhydride structure secreted by many species of blister beetle, and most notably by the Spanish fly, Lytta vesicatoria. Natural toxin inhibitor of protein phosphatases 1 and 2A.		2.7330cyclic dicarboxylic anhydride;
monoterpenoid		EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
herbicide
alanine
Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.. alanine : An alpha-amino acid that consists of propionic acid bearing an amino substituent at position 2.		1.9810alanine zwitterion;
alanine;
L-alpha-amino acid;
proteinogenic amino acid;
pyruvate family amino acid		EC 4.3.1.15 (diaminopropionate ammonia-lyase) inhibitor;
fundamental metabolite
serine
Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.. serine : An alpha-amino acid that is alanine substituted at position 3 by a hydroxy group.		4.411L-alpha-amino acid;
proteinogenic amino acid;
serine family amino acid;
serine zwitterion;
serine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
aspartic acid
Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.. aspartic acid : An alpha-amino acid that consists of succinic acid bearing a single alpha-amino substituent. L-aspartic acid : The L-enantiomer of aspartic acid.		2.4620aspartate family amino acid;
aspartic acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
mouse metabolite;
neurotransmitter
glutamine
Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.. L-glutamine : An optically active form of glutamine having L-configuration.. glutamine : An alpha-amino acid that consists of butyric acid bearing an amino substituent at position 2 and a carbamoyl substituent at position 4.		6.3553amino acid zwitterion;
glutamine family amino acid;
glutamine;
L-alpha-amino acid;
polar amino acid zwitterion;
proteinogenic amino acid		EC 1.14.13.39 (nitric oxide synthase) inhibitor;
Escherichia coli metabolite;
human metabolite;
metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
cyanides
Cyanides: Inorganic salts of HYDROGEN CYANIDE containing the -CN radical. The concept also includes isocyanides. It is distinguished from NITRILES, which denotes organic compounds containing the -CN radical.. cyanides : Salts and C-organyl derivatives of hydrogen cyanide, HC#N.. isocyanide : The isomer HN(+)#C(-) of hydrocyanic acid, HC#N, and its hydrocarbyl derivatives RNC (RN(+)#C(-)).. cyanide : A pseudohalide anion that is the conjugate base of hydrogen cyanide.		1.9710pseudohalide anionEC 1.9.3.1 (cytochrome c oxidase) inhibitor
sucrose
Saccharum: A plant genus of the family POACEAE widely cultivated in the tropics for the sweet cane that is processed into sugar.		7.7130glycosyl glycosidealgal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
osmolyte;
Saccharomyces cerevisiae metabolite;
sweetening agent
9,10-dimethyl-1,2-benzanthracene
9,10-Dimethyl-1,2-benzanthracene: Polycyclic aromatic hydrocarbon found in tobacco smoke that is a potent carcinogen.. 7,12-dimethyltetraphene : A tetraphene having methyl substituents at the 7- and 12-positions. It is a potent carcinogen and is present in tobacco smoke.		2.1710ortho-fused polycyclic arene;
tetraphenes		carcinogenic agent
adenosine diphosphate
Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.		2.920adenosine 5'-phosphate;
purine ribonucleoside 5'-diphosphate		fundamental metabolite;
human metabolite
triphenylethylene
[no description available]		1.9910stilbenoid
uridine monophosphate
Uridine Monophosphate: 5'-Uridylic acid. A uracil nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position.. uridine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having uracil as the nucleobase.		2.1110pyrimidine ribonucleoside 5'-monophosphate;
uridine 5'-phosphate		Escherichia coli metabolite;
human metabolite;
mouse metabolite
bromodeoxyuridine
Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.		3.8440pyrimidine 2'-deoxyribonucleosideantimetabolite;
antineoplastic agent
carbostyril
Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.		4.5351monohydroxyquinoline;
quinolone		bacterial xenobiotic metabolite
edetic acid
Edetic Acid: A chelating agent that sequesters a variety of polyvalent cations such as CALCIUM. It is used in pharmaceutical manufacturing and as a food additive.		6.38153ethylenediamine derivative;
polyamino carboxylic acid;
tetracarboxylic acid		anticoagulant;
antidote;
chelator;
copper chelator;
geroprotector
tyrosine
Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.. tyrosine : An alpha-amino acid that is phenylalanine bearing a hydroxy substituent at position 4 on the phenyl ring.		3.8721amino acid zwitterion;
erythrose 4-phosphate/phosphoenolpyruvate family amino acid;
L-alpha-amino acid;
proteinogenic amino acid;
tyrosine		EC 1.3.1.43 (arogenate dehydrogenase) inhibitor;
fundamental metabolite;
micronutrient;
nutraceutical
adenosine monophosphate
Adenosine Monophosphate: Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.		2.4120adenosine 5'-phosphate;
purine ribonucleoside 5'-monophosphate		adenosine A1 receptor agonist;
cofactor;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
EC 3.1.3.11 (fructose-bisphosphatase) inhibitor;
fundamental metabolite;
micronutrient;
nutraceutical
methylene blue
Methylene Blue: A compound consisting of dark green crystals or crystalline powder, having a bronze-like luster. Solutions in water or alcohol have a deep blue color. Methylene blue is used as a bacteriologic stain and as an indicator. It inhibits GUANYLATE CYCLASE, and has been used to treat cyanide poisoning and to lower levels of METHEMOGLOBIN.. methylene blue : An organic chloride salt having 3,7-bis(dimethylamino)phenothiazin-5-ium as the counterion. A commonly used dye that also exhibits antioxidant, antimalarial, antidepressant and cardioprotective properties.		2.4620organic chloride saltacid-base indicator;
antidepressant;
antimalarial;
antimicrobial agent;
antioxidant;
cardioprotective agent;
EC 1.4.3.4 (monoamine oxidase) inhibitor;
EC 3.1.1.8 (cholinesterase) inhibitor;
EC 4.6.1.2 (guanylate cyclase) inhibitor;
fluorochrome;
histological dye;
neuroprotective agent;
physical tracer
leucine
Leucine: An essential branched-chain amino acid important for hemoglobin formation.. leucine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isobutyl group.		2.0810amino acid zwitterion;
L-alpha-amino acid;
leucine;
proteinogenic amino acid;
pyruvate family amino acid		algal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
cytidine monophosphate
Cytidine Monophosphate: Cytidine (dihydrogen phosphate). A cytosine nucleotide containing one phosphate group esterified to the sugar moiety in the 2', 3' or 5' position.. cytidine 5'-monophosphate : A pyrimidine ribonucleoside 5'-monophosphate having cytosine as the nucleobase.		3.8521cytidine 5'-phosphate;
pyrimidine ribonucleoside 5'-monophosphate		Escherichia coli metabolite;
human metabolite;
mouse metabolite
methionine
Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.. methionine : A sulfur-containing amino acid that is butyric acid bearing an amino substituent at position 2 and a methylthio substituent at position 4.		3.73100aspartate family amino acid;
L-alpha-amino acid;
methionine zwitterion;
methionine;
proteinogenic amino acid		antidote to paracetamol poisoning;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical
1,2-dipalmitoylphosphatidylcholine
1,2-Dipalmitoylphosphatidylcholine: Synthetic phospholipid used in liposomes and lipid bilayers to study biological membranes. It is also a major constituent of PULMONARY SURFACTANTS.		2.4720
phenylalanine
Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.. L-phenylalanine : The L-enantiomer of phenylalanine.. phenylalanine : An aromatic amino acid that is alanine in which one of the methyl hydrogens is substituted by a phenyl group.		1.9910amino acid zwitterion;
erythrose 4-phosphate/phosphoenolpyruvate family amino acid;
L-alpha-amino acid;
phenylalanine;
proteinogenic amino acid		algal metabolite;
EC 3.1.3.1 (alkaline phosphatase) inhibitor;
Escherichia coli metabolite;
human xenobiotic metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
colchicine
(S)-colchicine : A colchicine that has (S)-configuration. It is a secondary metabolite, has anti-inflammatory properties and is used to treat gout, crystal-induced joint inflammation, familial Mediterranean fever, and many other conditions.		3.1210alkaloid;
colchicine		anti-inflammatory agent;
gout suppressant;
mutagen
cytidine
[no description available]		3.4811cytidinesEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
cytidine triphosphate
Cytidine Triphosphate: Cytidine 5'-(tetrahydrogen triphosphate). A cytosine nucleotide containing three phosphate groups esterified to the sugar moiety.		2.9610cytidine 5'-phosphate;
pyrimidine ribonucleoside 5'-triphosphate		Escherichia coli metabolite;
mouse metabolite
cycloheximide
Cycloheximide: Antibiotic substance isolated from streptomycin-producing strains of Streptomyces griseus. It acts by inhibiting elongation during protein synthesis.. cycloheximide : A dicarboximide that is 4-(2-hydroxyethyl)piperidine-2,6-dione in which one of the hydrogens attached to the carbon bearing the hydroxy group is replaced by a 3,5-dimethyl-2-oxocyclohexyl group. It is an antibiotic produced by the bacterium Streptomyces griseus.		2.0210antibiotic fungicide;
cyclic ketone;
dicarboximide;
piperidine antibiotic;
piperidones;
secondary alcohol		anticoronaviral agent;
bacterial metabolite;
ferroptosis inhibitor;
neuroprotective agent;
protein synthesis inhibitor
ficusin
Ficusin: A naturally occurring furocoumarin, found in PSORALEA. After photoactivation with UV radiation, it binds DNA via single and double-stranded cross-linking.. psoralen : The simplest member of the class of psoralens that is 7H-furo[3,2-g]chromene having a keto group at position 7. It has been found in plants like Psoralea corylifolia and Ficus salicifolia.		210psoralensplant metabolite
egtazic acid
Egtazic Acid: A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.. ethylene glycol bis(2-aminoethyl)tetraacetic acid : A diether that is ethylene glycol in which the hydrogens of the hydroxy groups have been replaced by 2-[bis(carboxymethyl)amino]ethyl group respectively.		210diether;
tertiary amino compound;
tetracarboxylic acid		chelator
dimethylformamide
Dimethylformamide: A formamide in which the amino hydrogens are replaced by methyl groups.. N,N-dimethylformamide : A member of the class of formamides that is formamide in which the amino hydrogens are replaced by methyl groups.		1.9910formamides;
volatile organic compound		geroprotector;
hepatotoxic agent;
polar aprotic solvent
tubercidin
Tubercidin: An antibiotic purine ribonucleoside that readily substitutes for adenosine in the biological system, but its incorporation into DNA and RNA has an inhibitory effect on the metabolism of these nucleic acids.. tubercidin : An N-glycosylpyrrolopyrimidine that is adenosine in which the in the 5-membered ring that is not attached to the ribose moiety is replaced by a carbon. Tubercidin is produced in the culture broth of Streptomyces tubericidus.		2.0710antibiotic antifungal agent;
N-glycosylpyrrolopyrimidine;
ribonucleoside		antimetabolite;
antineoplastic agent;
bacterial metabolite
ampicillin
Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broad-spectrum antibiotic.. ampicillin : A penicillin in which the substituent at position 6 of the penam ring is a 2-amino-2-phenylacetamido group.		2.1110beta-lactam antibiotic;
penicillin allergen;
penicillin		antibacterial drug
mannitol
[no description available]		5.7261mannitolallergen;
antiglaucoma drug;
compatible osmolytes;
Escherichia coli metabolite;
food anticaking agent;
food bulking agent;
food humectant;
food stabiliser;
food thickening agent;
hapten;
metabolite;
osmotic diuretic;
sweetening agent
cytarabine
[no description available]		15.859529beta-D-arabinoside;
monosaccharide derivative;
pyrimidine nucleoside		antimetabolite;
antineoplastic agent;
antiviral agent;
immunosuppressive agent
ornithine
Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine.. ornithine : An alpha-amino acid that is pentanoic acid bearing two amino substituents at positions 2 and 5.		3.0610non-proteinogenic L-alpha-amino acid;
ornithine		algal metabolite;
hepatoprotective agent;
mouse metabolite
asparagine
Asparagine: A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed). asparagine : An alpha-amino acid in which one of the hydrogens attached to the alpha-carbon of glycine is substituted by a 2-amino-2-oxoethyl group.		1.9910amino acid zwitterion;
asparagine;
aspartate family amino acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
histidine
Histidine: An essential amino acid that is required for the production of HISTAMINE.. L-histidine : The L-enantiomer of the amino acid histidine.. histidine : An alpha-amino acid that is propanoic acid bearing an amino substituent at position 2 and a 1H-imidazol-4-yl group at position 3.		6.181amino acid zwitterion;
histidine;
L-alpha-amino acid;
polar amino acid zwitterion;
proteinogenic amino acid		algal metabolite;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
medroxyprogesterone acetate
[no description available]		9.133120-oxo steroid;
3-oxo-Delta(4) steroid;
acetate ester;
corticosteroid;
steroid ester		adjuvant;
androgen;
antineoplastic agent;
antioxidant;
female contraceptive drug;
inhibitor;
progestin;
synthetic oral contraceptive
valine
Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.. valine : A branched-chain amino acid that consists of glycine in which one of the hydrogens attached to the alpha-carbon is substituted by an isopropyl group.. L-valine : The L-enantiomer of valine.		2.110L-alpha-amino acid zwitterion;
L-alpha-amino acid;
proteinogenic amino acid;
pyruvate family amino acid;
valine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
threonine
Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.. threonine : An alpha-amino acid in which one of the hydrogens attached to the alpha-carbon of glycine is substituted by a 1-hydroxyethyl group.		2.1710amino acid zwitterion;
aspartate family amino acid;
L-alpha-amino acid;
proteinogenic amino acid;
threonine		algal metabolite;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
dichlorodiphenyldichloroethane
Dichlorodiphenyldichloroethane: An organochlorine insecticide that is slightly irritating to the skin. (From Merck Index, 11th ed, p482)		210chlorophenylethane;
monochlorobenzenes;
organochlorine insecticide		xenobiotic metabolite
tryptophan
Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.. tryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3.		2.7930erythrose 4-phosphate/phosphoenolpyruvate family amino acid;
L-alpha-amino acid zwitterion;
L-alpha-amino acid;
proteinogenic amino acid;
tryptophan zwitterion;
tryptophan		antidepressant;
Escherichia coli metabolite;
human metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
plant metabolite;
Saccharomyces cerevisiae metabolite
n,n'-diphenyl-4-phenylenediamine
N,N'-diphenyl-4-phenylenediamine: in veterinary medicine, has been used to prevent vitamin E deficiency in lambs; structure. N,N'-diphenyl-1,4-phenylenediamine : An N-substituted diamine that is 1,4-phenylenediamine in which one hydrogen from each amino group is replaced by a phenyl group.		1.9710N-substituted diamine;
secondary amino compound		antioxidant
arginine
Arginine: An essential amino acid that is physiologically active in the L-form.. arginine : An alpha-amino acid that is glycine in which the alpha-is substituted by a 3-guanidinopropyl group.		2.4720arginine;
glutamine family amino acid;
L-alpha-amino acid;
proteinogenic amino acid		biomarker;
Escherichia coli metabolite;
micronutrient;
mouse metabolite;
nutraceutical
ethylene
Plastipore: high density polyethylene sponge biocompatible material; used as posts in dental bridges		4.6111alkene;
gas molecular entity		plant hormone;
refrigerant
trichloroacetic acid
Trichloroacetic Acid: A strong acid used as a protein precipitant in clinical chemistry and also as a caustic for removing warts.. trichloroacetic acid : A monocarboxylic acid that is acetic acid in which all three methyl hydrogens are substituted by chlorine.		1.9910monocarboxylic acid;
organochlorine compound		carcinogenic agent;
metabolite;
mouse metabolite
fluoxymesterone
Fluoxymesterone: An anabolic steroid that has been used in the treatment of male HYPOGONADISM, delayed puberty in males, and in the treatment of breast neoplasms in women.		3.361111beta-hydroxy steroid;
17beta-hydroxy steroid;
3-oxo-Delta(4) steroid;
anabolic androgenic steroid;
fluorinated steroid		anabolic agent;
antineoplastic agent
dichloroacetic acid
[no description available]		7.5720monocarboxylic acid;
organochlorine compound		astringent;
marine metabolite
pantothenic acid
Pantothenic Acid: A butyryl-beta-alanine that can also be viewed as pantoic acid complexed with BETA ALANINE. It is incorporated into COENZYME A and protects cells against peroxidative damage by increasing the level of GLUTATHIONE.. pantothenic acid : A member of the class of pantothenic acids that is an amide formed from pantoic acid and beta-alanine.. vitamin B5 : Any member of a group of vitamers that belong to the chemical structural class called pantothenic acids that exhibit biological activity against vitamin B5 deficiency. Deficiency of vitamin B5 is rare due to its widespread distribution in whole grain cereals, legumes and meat. Symptoms associated with vitamin B5 deficiency are difficult to asses since they are subtle and resemble those of other B vitamin deficiencies. The vitamers include (R)-pantothenic acid and its ionized and salt forms.. (R)-pantothenate : A pantothenate that is the conjugate base of (R)-pantothenic acid, obtained by deprotonation of the carboxy group.. (R)-pantothenic acid : A pantothenic acid having R-configuration.		4.3422pantothenic acid;
vitamin B5		antidote to curare poisoning;
geroprotector;
human blood serum metabolite
methylprednisolone
Methylprednisolone: A PREDNISOLONE derivative with similar anti-inflammatory action.. 6alpha-methylprednisolone : The 6alpha-stereoisomer of 6-methylprednisolone.		14.321776-methylprednisolone;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		adrenergic agent;
anti-inflammatory drug;
antiemetic;
environmental contaminant;
neuroprotective agent;
xenobiotic
quinoxalines
quinoxaline : A naphthyridine in which the nitrogens are at positions 1 and 4.		6.522mancude organic heterobicyclic parent;
naphthyridine;
ortho-fused heteroarene
xanthenes
Xanthenes: Compounds with three aromatic rings in linear arrangement with an OXYGEN in the center ring.		2.4620xanthene
trehalose
alpha,alpha-trehalose : A trehalose in which both glucose residues have alpha-configuration at the anomeric carbon.		2.0710trehaloseEscherichia coli metabolite;
geroprotector;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
phenylhydrazine
[no description available]		2.0110phenylhydrazinesxenobiotic
quinuclidines
Quinuclidines: A class of organic compounds which contain two rings that share a pair of bridgehead carbon atoms and contains an amine group.		8.19138quinuclidines;
saturated organic heterobicyclic parent
pyridostigmine bromide
Pyridostigmine Bromide: A cholinesterase inhibitor with a slightly longer duration of action than NEOSTIGMINE. It is used in the treatment of myasthenia gravis and to reverse the actions of muscle relaxants.		2.0310pyridinium salt
caprolactam
Caprolactam: Cyclic amide of caproic acid used in manufacture of synthetic fibers of the polyamide type. Can cause local irritation.. epsilon-caprolactam : A member of the class of caprolactams that is azepane substituted by an oxo group at position 2.		4.6111caprolactamshuman blood serum metabolite
glyoxal
[no description available]		3.1410dialdehydeagrochemical;
allergen;
pesticide;
plant growth regulator
2-methylpentane
Hexanes: Six-carbon saturated hydrocarbon group of the methane series. Include isomers and derivatives. Various polyneuropathies are caused by hexane poisoning.		2.3110alkane
pyrroles
1H-pyrrole : A tautomer of pyrrole that has the double bonds at positions 2 and 4.. pyrrole : A five-membered monocyclic heteroarene comprising one NH and four CH units which forms the parent compound of the pyrrole group of compounds. Its five-membered ring structure has three tautomers. A 'closed class'.. azole : Any monocyclic heteroarene consisting of a five-membered ring containing nitrogen. Azoles can also contain one or more other non-carbon atoms, such as nitrogen, sulfur or oxygen.		11.982718pyrrole;
secondary amine
thiophenes
Thiophenes: A monocyclic heteroarene furan in which the oxygen atom is replaced by a sulfur.. thiophenes : Compounds containing at least one thiophene ring.		7.6152mancude organic heteromonocyclic parent;
monocyclic heteroarene;
thiophenes;
volatile organic compound		non-polar solvent
isopropyl myristate
isopropyl myristate: used for microemulsions; structure		4.9821fatty acid ester
3,4-dihydropyran
[no description available]		2.1110
trinitrotoluene
Trinitrotoluene: A 2,4,6-trinitrotoluene, which is an explosive chemical that can cause skin irritation and other toxic consequences.. 2,4,6-trinitrotoluene : A trinitrotoluene having the nitro groups at positions 2, 4 and 6.		2.1710trinitrotolueneexplosive
framycetin
Framycetin: A component of NEOMYCIN that is produced by Streptomyces fradiae. On hydrolysis it yields neamine and neobiosamine B. (From Merck Index, 11th ed). framycetin : A tetracyclic antibacterial agent derived from neomycin, being a glycoside ester of neamine and neobiosamine B.		4.3322aminoglycosideallergen;
antibacterial drug;
Escherichia coli metabolite
fluorodeoxyuridylate
Fluorodeoxyuridylate: 5-Fluoro-2'-deoxyuridylate. An inhibitor of thymidylate synthetase. Formed from 5-fluorouracil or 5-fluorodeoxyuridine.		1.9810pyrimidine 2'-deoxyribonucleoside 5'-monophosphate
ditiocarb
Ditiocarb: A chelating agent that has been used to mobilize toxic metals from the tissues of humans and experimental animals. It is the main metabolite of DISULFIRAM.. diethyldithiocarbamic acid : A member of the class of dithiocarbamic acids that is diethylcarbamic acid in which both of the oxygens are replaced by sulfur.		5.17111dithiocarbamic acidschelator;
copper chelator
quinazolines
Quinazolines: A group of aromatic heterocyclic compounds that contain a bicyclic structure with two fused six-membered aromatic rings, a benzene ring and a pyrimidine ring.. quinazoline : A mancude organic heterobicyclic parent that is naphthalene in which the carbon atoms at positions 1 and 3 have been replaced by nitrogen atoms.. quinazolines : Any organic heterobicyclic compound based on a quinazoline skeleton and its substituted derivatives.		21.61231150azaarene;
mancude organic heterobicyclic parent;
ortho-fused heteroarene;
quinazolines
acridines
Acridines: Compounds that include the structure of acridine.. acridine : A polycyclic heteroarene that is anthracene in which one of the central CH groups is replaced by a nitrogen atom.		5.9233acridines;
mancude organic heterotricyclic parent;
polycyclic heteroarene		genotoxin
indazoles
Indazoles: A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.		12.392212indazole
benzoxazoles
1,3-benzoxazole : A benzoxazole in which the benzene ring is fused to a 1,3-oxazole ring across positions 4 and 5.. benzoxazole : Compounds based on a fused 1,2- or 1,3-oxazole and benzene bicyclic ring skeleton.		4.61111,3-benzoxazoles;
mancude organic heterobicyclic parent
adamantane
Adamantane: A tricyclo bridged hydrocarbon.		2.5420adamantanes;
polycyclic alkane
cyclopentane
Cyclopentanes: A group of alicyclic hydrocarbons with the general formula R-C5H9.. cyclopentanes : Cyclopentane and its derivatives formed by substitution.		4.231cycloalkane;
cyclopentanes;
volatile organic compound		non-polar solvent
oxazoles
Oxazoles: Five-membered heterocyclic ring structures containing an oxygen in the 1-position and a nitrogen in the 3-position, in distinction from ISOXAZOLES where they are at the 1,2 positions.. 1,3-oxazole : A five-membered monocyclic heteroarene that is an analogue of cyclopentadiene with O in place of CH2 at position 1 and N in place of CH at position 3.. oxazole : An azole based on a five-membered heterocyclic aromatic skeleton containing one N and one O atom.		2101,3-oxazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
thiazoles
[no description available]		8.972041,3-thiazoles;
mancude organic heteromonocyclic parent;
monocyclic heteroarene
pyrazines
Pyrazines: A heterocyclic aromatic organic compound with the chemical formula C4H4N2.. pyrazine : A diazine that is benzene in which the carbon atoms at positions 1 and 4 have been replaced by nitrogen atoms.		11.762715diazine;
pyrazines		Daphnia magna metabolite
hydrazine
diamine : Any polyamine that contains two amino groups.		9.3275azane;
hydrazines		EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor
evans blue
Evans Blue: An azo dye used in blood volume and cardiac output measurement by the dye dilution method. It is very soluble, strongly bound to plasma albumin, and disappears very slowly.. Evans blue : An organic sodium salt that is the tetrasodium salt of 6,6'-{(3,3'-dimethyl[1,1'-biphenyl]-4,4'-diyl)bis[diazene-2,1-diyl]}bis(4-amino-5-hydroxynaphthalene-1,3-disulfonate). It is sometimes used as a counterstain, especially in fluorescent methods to suppress background autofluorescence.		2.0510organic sodium saltfluorochrome;
histological dye;
sodium channel blocker;
teratogenic agent
azacitidine
Azacitidine: A pyrimidine analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent.. 5-azacytidine : An N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-ribofuranosyl residue via an N-glycosidic linkage. An antineoplastic agent, it is used in the treatment of myeloid leukaemia.		11.912211N-glycosyl-1,3,5-triazine;
nucleoside analogue		antineoplastic agent
thymidine monophosphate
Thymidine Monophosphate: 5-Thymidylic acid. A thymine nucleotide containing one phosphate group esterified to the deoxyribose moiety.. dTMP : The neutral species of thymidine 5'-monophosphate (2'-deoxythymidine 5'-monophosphate).		210thymidine 5'-monophosphatefundamental metabolite
fluorobenzenes
Fluorobenzenes: Derivatives of BENZENE that contain FLUORINE.. monofluorobenzene : The simplest member of the class of monofluorobenzenes that is benzene carrying a single fluoro substituent.. fluorobenzenes : Any fluoroarene that is a benzene or a substituted benzene carrying at least one fluoro group.		2.0410monofluorobenzenesNMR chemical shift reference compound
funiculosin (anthraquinone)
funiculosin (anthraquinone): see also a pyridone cpd called funiculosin; structure		1.9710trihydroxyanthraquinone
plumbagin
plumbagin: a superoxide anion generator. plumbagin : A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone in which the hydrogens at positions 2 and 5 are substituted by methyl and hydroxy groups, respectively.		2.1310hydroxy-1,4-naphthoquinone;
phenols		anticoagulant;
antineoplastic agent;
immunological adjuvant;
metabolite
reticulin
Reticulin: A scleroprotein fibril consisting mostly of type III collagen. Reticulin fibrils are extremely thin, with a diameter of between 0.5 and 2 um. They are involved in maintaining the structural integrity in a variety of organs.		210benzylisoquinoline alkaloid;
benzyltetrahydroisoquinoline;
isoquinolinol		plant metabolite
caprolactone
hexano-6-lactone : A epsilon-lactone that is oxepane substituted by an oxo group at position 2.		7.5220epsilon-lactone
alpha-aminopyridine
alpha-aminopyridine: RN given refers to parent cpd; structure in Merck Index, 9th ed, #485. aminopyridine : Compounds containing a pyridine skeleton substituted by one or more amine groups.		8.57104
oleanolic acid
[no description available]		2.3110hydroxy monocarboxylic acid;
pentacyclic triterpenoid		plant metabolite
podophyllotoxin
Podophyllum: A genus of poisonous American herbs, family BERBERIDACEAE. The roots yield PODOPHYLLOTOXIN and other pharmacologically important agents. The plant was formerly used as a cholagogue and cathartic. It is different from the European mandrake, MANDRAGORA.		12.2994furonaphthodioxole;
lignan;
organic heterotetracyclic compound		antimitotic;
antineoplastic agent;
keratolytic drug;
microtubule-destabilising agent;
plant metabolite;
tubulin modulator
medroxyprogesterone
[no description available]		2.924017alpha-hydroxy steroid;
20-oxo steroid;
3-oxo-Delta(4) steroid;
tertiary alpha-hydroxy ketone		contraceptive drug;
progestin;
synthetic oral contraceptive
azomycin
azomycin: RN given refers to parent cpd with specified locant; structure		2.9240C-nitro compound;
imidazoles		antitubercular agent
methoxyhydroxyphenylglycol
Methoxyhydroxyphenylglycol: Synthesized from endogenous epinephrine and norepinephrine in vivo. It is found in brain, blood, CSF, and urine, where its concentrations are used to measure catecholamine turnover.		1.9710methoxybenzenes;
phenols
muscone
muscone: structure in first source		4.6111
malondialdehyde
Malondialdehyde: The dialdehyde of malonic acid.. malonaldehyde : A dialdehyde that is propane substituted by two oxo groups at the terminal carbon atoms respectively. A biomarker of oxidative damage to lipids caused by smoking, it exists in vivo mainly in the enol form.		3.6490dialdehydebiomarker
triethylenephosphoramide
Triethylenephosphoramide: An insect chemosterilant and an antineoplastic agent.		5.2441phosphoramide
hematoporphyrin
Hematoporphyrins: Iron-free derivatives of heme with 4 methyl groups, 2 hydroxyethyl groups and 2 propionic acid groups attached to the pyrrole rings. Some of these PHOTOSENSITIZING AGENTS are used in the PHOTOTHERAPY of malignant NEOPLASMS.. hematoporphyrin : A dicarboxylic acid that is protoporphyrin in which the vinyl groups at positions 7 and 12 are replaced by 1-hydroxyethyl groups.		2.0110
lithium carbonate
Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of BIOGENIC MONOAMINES in the CENTRAL NERVOUS SYSTEM, and affects multiple neurotransmission systems.		7.0510carbonate salt;
lithium salt		antimanic drug
docusate
Dioctyl Sulfosuccinic Acid: All-purpose surfactant, wetting agent, and solubilizer used in the drug, cosmetics, and food industries. It has also been used in laxatives and as cerumenolytics. It is usually administered as either the calcium, potassium, or sodium salt.		2.0610diester;
organosulfonic acid
megestrol acetate
[no description available]		5.055220-oxo steroid;
3-oxo-Delta(4) steroid;
acetate ester;
steroid ester		antineoplastic agent;
appetite enhancer;
contraceptive drug;
progestin;
synthetic oral contraceptive
galactitol
[no description available]		3.0610hexitolEscherichia coli metabolite;
human metabolite;
metabolite;
mouse metabolite
acetylcysteine
N-acetyl-L-cysteine : An N-acetyl-L-amino acid that is the N-acetylated derivative of the natural amino acid L-cysteine.		12.09102acetylcysteine;
L-cysteine derivative;
N-acetyl-L-amino acid		antidote to paracetamol poisoning;
antiinfective agent;
antioxidant;
antiviral drug;
ferroptosis inhibitor;
geroprotector;
human metabolite;
mucolytic;
radical scavenger;
vulnerary
c.i. 42510
Rosaniline Dyes: Compounds that contain the triphenylmethane aniline structure found in rosaniline. Many of them have a characteristic magenta color and are used as COLORING AGENTS.. basic fuchsin : A four-component mixture of chemically related dyes comprising pararosanilin, rosanilin, magenta II and new fuchsin in varying amounts. rosanilin : A hydrochloride that is the monohydrochloride of 4-[(4-aminophenyl)(4-iminocyclohexa-2,5-dien-1-ylidene)methyl]-2-methylaniline. One of the major constituents of Basic fuchsin, together with pararosanilin, magenta II and new fuchsin.		1.9710
methylnitrosourea
Methylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.. N-methyl-N-nitrosourea : A member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by methyl and nitroso groups.		4.3711N-nitrosoureasalkylating agent;
carcinogenic agent;
mutagen;
teratogenic agent
ethylnitrosourea
Ethylnitrosourea: A nitrosourea compound with alkylating, carcinogenic, and mutagenic properties.. N-ethyl-N-nitrosourea : A member of the class of N-nitrosoureas that is urea in which one of the nitrogens is substituted by ethyl and nitroso groups.		2.5220N-nitrosoureasalkylating agent;
carcinogenic agent;
genotoxin;
mutagen
alpha-fluoro-beta-alanine
alpha-fluoro-beta-alanine: metabolite of HCFU & 5-fluorouracil; structure in first source		210organonitrogen compound;
organooxygen compound
hydroxyethyl methacrylate
hydroxyethyl methacrylate: many of cited refs are for gel which refers to polymeric form of above cpd: POLYHYDROXYETHYL METHACRYLATE. 2-hydroxyethyl methacrylate : An enoate ester that is the monomethacryloyl derivative of ethylene glycol.		2.0410enoate esterallergen;
polymerisation monomer
deoxycytidine
[no description available]		26.4941408pyrimidine 2'-deoxyribonucleosideEscherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
durapatite
Durapatite: The mineral component of bones and teeth; it has been used therapeutically as a prosthetic aid and in the prevention and treatment of osteoporosis.. hydroxylapatite : A phosphate mineral with the formula Ca5(PO4)3(OH).		2.5220
zinc oxide
Zinc Oxide: A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock.		2.3110zinc molecular entity
arsenic trioxide
Arsenic Trioxide: An inorganic compound with the chemical formula As2O3 that is used for the treatment of ACUTE PROMYELOCYTIC LEUKEMIA in patients who have relapsed from, or are resistant to, conventional drug therapy.		8.8721
sorbitan monostearate
sorbitan monostearate: Stearic Acid was the HM (74-82), no longer an active MH		2.110
vancomycin
Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.. vancomycin : A complex glycopeptide from Streptomyces orientalis. It inhibits a specific step in the synthesis of the peptidoglycan layer in the Gram-positive bacteria Staphylococcus aureus and Clostridium difficile.		2.5420glycopeptideantibacterial drug;
antimicrobial agent;
bacterial metabolite
d-alpha tocopherol
Vitamin E: A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.. tocopherol : A collective name for a group of closely related lipids that contain a chroman-6-ol nucleus substituted at position 2 by a methyl group and by a saturated hydrocarbon chain consisting of three isoprenoid units. They are designated as alpha-, beta-, gamma-, and delta-tocopherol depending on the number and position of additional methyl substituents on the aromatic ring. Tocopherols occur in vegetable oils and vegetable oil products, almost exclusively with R,R,R configuration. Tocotrienols differ from tocopherols only in having three double bonds in the hydrocarbon chain.. vitamin E : Any member of a group of fat-soluble chromanols that exhibit biological activity against vitamin E deficiency. The vitamers in this class consists of a chroman-6-ol core which is substituted at position 2 by a methyl group and (also at position 2) either a saturated or a triply-unsaturated hydrocarbon chain consisting of three isoprenoid units. The major function of vitamin E is to act as a natural antioxidant by scavenging free radicals and molecular oxygen.. (R,R,R)-alpha-tocopherol : An alpha-tocopherol that has R,R,R configuration. The naturally occurring stereoisomer of alpha-tocopherol, it is found particularly in sunflower and olive oils.		2.610alpha-tocopherolalgal metabolite;
antiatherogenic agent;
anticoagulant;
antioxidant;
antiviral agent;
EC 2.7.11.13 (protein kinase C) inhibitor;
immunomodulator;
micronutrient;
nutraceutical;
plant metabolite
1,2-epoxyhexane
[no description available]		4.6111
selenomethionine
[no description available]		2.0510selenoamino acid;
selenomethionines		plant metabolite
paraquat
Paraquat: A poisonous dipyridilium compound used as contact herbicide. Contact with concentrated solutions causes irritation of the skin, cracking and shedding of the nails, and delayed healing of cuts and wounds.. paraquat : An organic cation that consists of 4,4'-bipyridine bearing two N-methyl substituents loctated at the 1- and 1'-positions.		2.2110organic cationgeroprotector;
herbicide
methionine sulfoximine
methionine sulfoximine : A non-proteinogenic alpha-amino acid that is the sulfoximine derivative of methionine .		3.2360methionine derivative;
non-proteinogenic alpha-amino acid;
sulfoximide
amiloride
Amiloride: A pyrazine compound inhibiting SODIUM reabsorption through SODIUM CHANNELS in renal EPITHELIAL CELLS. This inhibition creates a negative potential in the luminal membranes of principal cells, located in the distal convoluted tubule and collecting duct. Negative potential reduces secretion of potassium and hydrogen ions. Amiloride is used in conjunction with DIURETICS to spare POTASSIUM loss. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p705). amiloride : A member of the class of pyrazines resulting from the formal monoacylation of guanidine with the carboxy group of 3,5-diamino-6-chloropyrazine-2-carboxylic acid.		2.2110aromatic amine;
guanidines;
organochlorine compound;
pyrazines		diuretic;
sodium channel blocker
methylprednisolone hemisuccinate
Methylprednisolone Hemisuccinate: A water-soluble ester of METHYLPREDNISOLONE used for cardiac, allergic, and hypoxic emergencies.		3.3711corticosteroid hormone;
hemisuccinate
doxifluridine
doxifluridine : A pyrimidine 5'-deoxyribonucleoside that is 5-fluorouridine in which the hydroxy group at the 5' position is replaced by a hydrogen. It is an oral prodrug of the antineoplastic agent 5-fluorouracil. Designed to circumvent the rapid degradation of 5-fluorouracil by dihydropyrimidine dehydrogenase in the gut wall, it is converted into 5-fluorouracil in the presence of pyrimidine nucleoside phosphorylase.		3.2660organofluorine compound;
pyrimidine 5'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
prodrug
fluorescein-5-isothiocyanate
Fluorescein-5-isothiocyanate: Fluorescent probe capable of being conjugated to tissue and proteins. It is used as a label in fluorescent antibody staining procedures as well as protein- and amino acid-binding techniques.. fluorescein 5-isothiocyanate : The 5-isomer of fluorescein isothiocyanate. Acts as a fluorescent probe capable of being conjugated to tissue and proteins; used as a label in fluorescent antibody staining procedures as well as protein- and amino acid-binding techniques.		2.9740fluorescein isothiocyanate
sabinene
sabinene: RN given refers to cpd without isomeric designation. sabinene : A thujene that is a bicyclic monoterpene isolated from the essential oils of various plant species.		2.110thujeneplant metabolite
carbonates
Carbonates: Salts or ions of the theoretical carbonic acid, containing the radical CO2(3-). Carbonates are readily decomposed by acids. The carbonates of the alkali metals are water-soluble; all others are insoluble. (From Grant & Hackh's Chemical Dictionary, 5th ed). carbonates : Organooxygen compounds that are salts or esters of carbonic acid, H2CO3.		2.9640carbon oxoanion
cladribine
[no description available]		2.0510organochlorine compound;
purine 2'-deoxyribonucleoside		antineoplastic agent;
immunosuppressive agent
buthionine sulfoximine
Buthionine Sulfoximine: A synthetic amino acid that depletes glutathione by irreversibly inhibiting gamma-glutamylcysteine synthetase. Inhibition of this enzyme is a critical step in glutathione biosynthesis. It has been shown to inhibit the proliferative response in human T-lymphocytes and inhibit macrophage activation. (J Biol Chem 1995;270(33):1945-7). 2-amino-4-(S-butylsulfonimidoyl)butanoic acid : A non-proteinogenic alpha-amino acid that is homocysteine in which the thiol group carries an oxo, imino and butyl groups.. S-butyl-DL-homocysteine (S,R)-sulfoximine : A sulfoximide that is the sulfoximine derivative of an analogue of DL-methionine in which the S-methyl group is replaced by S-butyl.		3.95130diastereoisomeric mixture;
homocysteines;
non-proteinogenic alpha-amino acid;
sulfoximide		EC 6.3.2.2 (glutamate--cysteine ligase) inhibitor;
ferroptosis inducer
vidarabine
adenine arabinoside : A purine nucleoside in which adenine is attached to arabinofuranose via a beta-N(9)-glycosidic bond.		6.7783beta-D-arabinoside;
purine nucleoside		antineoplastic agent;
bacterial metabolite;
nucleoside antibiotic
iodinated glycerol
iodinated glycerol: secretolytic agent; RN given refers to cpd without iodine locant		2.730dioxolane
nimorazole
Nimorazole: An antitrichomonal agent which is effective either topically or orally and whose urinary metabolites are also trichomonicidal.		2.2510C-nitro compound;
imidazoles
iridium
Iridium: A metallic element with the atomic symbol Ir, atomic number 77, and atomic weight 192.22.		3.6820cobalt group element atom;
platinum group metal atom
manganese
Manganese: A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035). manganese(4+) : A manganese cation that is monoatomic and has a formal charge of +4.		2.1710elemental manganese;
manganese group element atom		Escherichia coli metabolite;
micronutrient
mercury
Mercury: A silver metallic element that exists as a liquid at room temperature. It has the atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to MERCURY POISONING. Because of its toxicity, the clinical use of mercury and mercurials is diminishing.. mercury(0) : Elemental mercury of oxidation state zero.		2.2110elemental mercury;
zinc group element atom		neurotoxin
molybdenum
Molybdenum: A metallic element with the atomic symbol Mo, atomic number 42, and atomic weight 95.95. It is an essential trace element, being a component of the enzymes xanthine oxidase, aldehyde oxidase, and nitrate reductase.		2.0510chromium group element atommicronutrient
palladium
Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys.. palladium : Chemical element (nickel group element atom) with atomic number 46.		8.830metal allergen;
nickel group element atom;
platinum group metal atom
platinum
Platinum: A heavy, soft, whitish metal, resembling tin, with atomic number 78, atomic weight 195.084, symbol Pt. It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as alutiae.		19.2732041elemental platinum;
nickel group element atom;
platinum group metal atom
rhenium
Rhenium: A metal, atomic number 75, atomic weight 186.207, symbol Re.		3.3110manganese group element atom
rhodium
Rhodium: A hard and rare metal of the platinum group, atomic number 45, atomic weight 102.905, symbol Rh.. rhodium atom : A cobalt group element atom of atomic number 45.		3.3110cobalt group element atom
ruthenium
Ruthenium: A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for PLATINUM and PALLADIUM.		4.1540iron group element atom;
platinum group metal atom
silver
Silver: An element with the atomic symbol Ag, atomic number 47, and atomic weight 107.87. It is a soft metal that is used medically in surgical instruments, dental prostheses, and alloys. Long-continued use of silver salts can lead to a form of poisoning known as ARGYRIA.		10.0321copper group element atom;
elemental silver		Escherichia coli metabolite
technetium
Technetium: The first artificially produced element and a radioactive fission product of URANIUM. Technetium has the atomic symbol Tc, and atomic number 43. All technetium isotopes are radioactive. Technetium 99m (m=metastable) which is the decay product of Molybdenum 99, has a half-life of about 6 hours and is used diagnostically as a radioactive imaging agent. Technetium 99 which is a decay product of technetium 99m, has a half-life of 210,000 years.		1.9810manganese group element atom
terbium
Terbium: An element of the rare earth family of metals. It has the atomic symbol Tb, atomic number 65, and atomic weight 158.92.		1.9710f-block element atom;
lanthanoid atom
thulium
Thulium: An element of the rare earth family of metals. It has the atomic symbol Tm, atomic number 69, and atomic weight 168.93.		4.6111f-block element atom;
lanthanoid atom
titanium
Titanium: A dark-gray, metallic element of widespread distribution but occurring in small amounts with atomic number, 22, atomic weight, 47.867 and symbol, Ti; specific gravity, 4.5; used for fixation of fractures.		4.6111titanium group element atom
cadmium
Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 112.41. It is a metal and ingestion will lead to CADMIUM POISONING.. elemental cadmium : An element in the zinc group of the periodic table with atomic number 48, atomic mass 112, M.P. 321degreeC, and B.P. 765degreeC). An odourless, tasteless, and highly poisonous soft, ductile, lustrous metal with electropositive properties. It has eight stable isotopes: (106)Cd, (108)Cd,(110)Cd, (111)Cd, (112)Cd, (113)Cd, (114)Cd and (116)Cd, with (112)Cd and (114)Cd being the most common.		2.9140cadmium molecular entity;
zinc group element atom
gadolinium
Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors.		5.0131f-block element atom;
lanthanoid atom
gold
Gold: A yellow metallic element with the atomic symbol Au, atomic number 79, and atomic weight 197. It is used in jewelry, goldplating of other metals, as currency, and in dental restoration. Many of its clinical applications, such as ANTIRHEUMATIC AGENTS, are in the form of its salts.		4.4760copper group element atom;
elemental gold
uranium
Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors.		4.6111actinoid atom;
f-block element atom;
monoatomic uranium
vanadium
Vanadium: A metallic element with the atomic symbol V, atomic number 23, and atomic weight 50.94. It is used in the manufacture of vanadium steel. Prolonged exposure can lead to chronic intoxication caused by absorption usually via the lungs.		7.1310elemental vanadium;
vanadium group element atom		micronutrient
yttrium
Yttrium: An element of the rare earth family of metals. It has the atomic symbol Y, atomic number 39, and atomic weight 88.91. In conjunction with other rare earths, yttrium is used as a phosphor in television receivers and is a component of the yttrium-aluminum garnet (YAG) lasers.		2.0510d-block element atom;
rare earth metal atom;
scandium group element atom
cupric chloride
cupric chloride: RN given refers to unlabeled parent cpd. copper(II) chloride : An inorganic chloride of copper in which the metal is in the +2 oxidation state.		2.0810copper molecular entity;
inorganic chloride		EC 5.3.3.5 (cholestenol Delta-isomerase) inhibitor
acetylglucosamine
Acetylglucosamine: The N-acetyl derivative of glucosamine.. N-acetyl-beta-D-glucosamine : An N-acetyl-D-glucosamine having beta-configuration at the anomeric centre.		2.0710N-acetyl-D-glucosamineepitope
camptothecin
NSC 100880: carboxylate (opened lactone) form of camptothecin; RN refers to (S)-isomer; structure given in first source		24.7221093delta-lactone;
pyranoindolizinoquinoline;
quinoline alkaloid;
tertiary alcohol		antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
genotoxin;
plant metabolite
barium sulfate
Barium Sulfate: A compound used as an x-ray contrast medium that occurs in nature as the mineral barite. It is also used in various manufacturing applications and mixed into heavy concrete to serve as a radiation shield.. barium sulfate : A metal sulfate with formula BaO4S. Virtually insoluble in water at room temperature, it is mostly used as a component in oil well drilling fluid it occurs naturally as the mineral barite.		4.3511barium salt;
inorganic barium salt;
metal sulfate		radioopaque medium
calcium phosphate, dibasic, anhydrous
calcium phosphate, dibasic, anhydrous: molecular formula CaHPO(4), DCPA=dicalcium phosphate anhydrous; don't confuse with dichloropropionanilide which also is called DCPA; MW=136.06; has greater surface area and lower pH than DCPD (dicalcium phosphate dihydrate); occurs in nature as monetite; an intermediate in preparing hydroxyapatite		2.3920calcium phosphate
calcium phosphate, monobasic, anhydrous
calcium phosphate, monobasic: MW 234.05		2.3920calcium phosphatefertilizer
tricalcium phosphate
tricalcium phosphate: a form of tricalcium phosphate used as bioceramic bone replacement material; see also records for alpha-tricalcium phosphate, beta-tricalcium phosphate, calcium phosphate; apatitic tricalcium phosphate Ca9(HPO4)(PO4)5(OH) is the calcium orthophosphate leading to beta tricalcium phosphate Ca3(PO4)2 (b-TCP). calcium phosphate : A calcium salt composed of calcium and phosphate/diphosphate ions; present in milk and used for the mineralisation of calcified tissues.		7.7130calcium phosphate
copper sulfate
Copper Sulfate: A sulfate salt of copper. It is a potent emetic and is used as an antidote for poisoning by phosphorus. It also can be used to prevent the growth of algae.. copper(II) sulfate : A metal sulfate compound having copper(2+) as the metal ion.		2.4420metal sulfateemetic;
fertilizer;
sensitiser
sodium thiosulfate
sodium thiosulfate: do not confuse synonym sodium hyposulfite with sodium hyposulfite, synonym for di-Na salt of dithionous acid. sodium thiosulfate : An inorganic sodium salt composed of sodium and thiosulfate ions in a 2:1 ratio.		5.06130inorganic sodium saltantidote to cyanide poisoning;
antifungal drug;
nephroprotective agent
calcium sulfate
Calcium Sulfate: A calcium salt that is used for a variety of purposes including: building materials, as a desiccant, in dentistry as an impression material, cast, or die, and in medicine for immobilizing casts and as a tablet excipient. It exists in various forms and states of hydration. Plaster of Paris is a mixture of powdered and heat-treated gypsum.		3.93100calcium salt;
inorganic calcium salt
fluorine
Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as fluoride (FLUORIDES) to prevent dental caries.		210diatomic fluorine;
gas molecular entity		NMR chemical shift reference compound
deuterium oxide
Deuterium Oxide: The isotopic compound of hydrogen of mass 2 (deuterium) with oxygen. (From Grant & Hackh's Chemical Dictionary, 5th ed) It is used to study mechanisms and rates of chemical or nuclear reactions, as well as biological processes.		210deuterated compound;
water		NMR solvent
galactose
aldohexose : A hexose with a (potential) aldehyde group at one end.		521
poloxalene
Poloxalene: A copolymer of polyethylene and polypropylene ether glycol. It is a non-ionic polyol surface-active agent used medically as a fecal softener and in cattle for prevention of bloat.. pluronic : A triblock copolymer composed of a central hydrophobic chain of poly(propylene oxide) flanked by two hydrophilic chains of poly(ethylene oxide).		2.4320epoxide
ozone
Ozone: The unstable triatomic form of oxygen, O3. It is a powerful oxidant that is produced for various chemical and industrial uses. Its production is also catalyzed in the ATMOSPHERE by ULTRAVIOLET RAY irradiation of oxygen or other ozone precursors such as VOLATILE ORGANIC COMPOUNDS and NITROGEN OXIDES. About 90% of the ozone in the atmosphere exists in the stratosphere (STRATOSPHERIC OZONE).. ozone : An elemental molecule with formula O3. An explosive, pale blue gas (b.p. -112degreeC) that has a characteristic, pungent odour, it is continuously produced in the upper atmosphere by the action of solar ultraviolet radiation on atmospheric oxygen. It is an antimicrobial agent used in the production of bottled water, as well as in the treatment of meat, poultry and other foodstuffs.		4.6111elemental molecule;
gas molecular entity;
reactive oxygen species;
triatomic oxygen		antiseptic drug;
disinfectant;
electrophilic reagent;
greenhouse gas;
mutagen;
oxidising agent;
tracer
cadmium chloride
Cadmium Chloride: A cadmium halide in the form of colorless crystals, soluble in water, methanol, and ethanol. It is used in photography, in dyeing, and calico printing, and as a solution to precipitate sulfides. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed). cadmium dichloride : A cadmium coordination entity in which cadmium(2+) and Cl(-) ions are present in the ratio 2:1. Although considered to be ionic, it has considerable covalent character to its bonding.		2.9340cadmium coordination entity
trolamine salicylate
Arthritis: Acute or chronic inflammation of JOINTS.		2.420
clodronic acid
Clodronic Acid: A diphosphonate which affects calcium metabolism. It inhibits bone resorption and soft tissue calcification.. clodronic acid : An organochlorine compound that is methylene chloride in which both hydrogens are replaced by phosphonic acid groups. It inhibits bone resorption and soft tissue calcification, and is used (often as the disodium salt tetrahydrate) as an adjunct in the treatment of severe hypercalcaemia associated with malignancy, and in the management of osteolytic lesions and bone pain associated with skeletal metastases.		1.99101,1-bis(phosphonic acid);
one-carbon compound;
organochlorine compound		antineoplastic agent;
bone density conservation agent
misonidazole
Misonidazole: A nitroimidazole that sensitizes normally radio-resistant hypoxic cells to radiation. It may also be directly cytotoxic to hypoxic cells and has been proposed as an antineoplastic.		2.420
1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea
1-(2-chloroethyl)-3-(2,6-dioxo-3-piperidinyl)-1-nitrosourea: structure		3.0610
metopimazine
metopimazine: RN given refers to parent cpd; structure		3.3811phenothiazines
technetium 99m
Technegas: ultrafine ventilatory agent; produced from technetium pertechnetate and graphite in an argon environment		1.9810technetium atom
clemastine
Clemastine: A histamine H1 antagonist used as the hydrogen fumarate in hay fever, rhinitis, allergic skin conditions, and pruritus. It causes drowsiness.. clemastine : 2-[(2R)-1-Methylpyrrolidin-2-yl]ethanol in which the hydrogen of the hydroxy group is substituted by a 1-(4-chlorophenyl)-1-phenylethyl group (R configuration). An antihistamine with antimuscarinic and moderate sedative properties, it is used as its fumarate salt for the symptomatic relief of allergic conditions such as rhinitis, urticaria, conjunctivitis and in pruritic (severe itching) skin conditions.		2.0110monochlorobenzenes;
N-alkylpyrrolidine		anti-allergic agent;
antipruritic drug;
H1-receptor antagonist;
muscarinic antagonist
cephalexin
Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of CEPHALORIDINE or CEPHALOTHIN, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms.. cephalexin : A semisynthetic first-generation cephalosporin antibiotic having methyl and beta-(2R)-2-amino-2-phenylacetamido groups at the 3- and 7- of the cephem skeleton, respectively. It is effective against both Gram-negative and Gram-positive organisms, and is used for treatment of infections of the skin, respiratory tract and urinary tract.		2.0510beta-lactam antibiotic allergen;
cephalosporin;
semisynthetic derivative		antibacterial drug
tetradecanoylphorbol acetate
Tetradecanoylphorbol Acetate: A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.. phorbol ester : Esters of phorbol, originally found in croton oil (from Croton tiglium, of the family Euphorbiaceae). A number of phorbol esters possess activity as tumour promoters and activate the mechanisms associated with cell growth. Some of these are used in experiments as activators of protein kinase C.. phorbol 13-acetate 12-myristate : A phorbol ester that is phorbol in which the hydroxy groups at the cyclopropane ring juction (position 13) and the adjacent carbon (position 12) have been converted into the corresponding acetate and myristate esters. It is a major active constituent of the seed oil of Croton tiglium. It has been used as a tumour promoting agent for skin carcinogenesis in rodents and is associated with increased cell proliferation of malignant cells. However its function is controversial since a decrease in cell proliferation has also been observed in several cancer cell types.		2.6830acetate ester;
diester;
phorbol ester;
tertiary alpha-hydroxy ketone;
tetradecanoate ester		antineoplastic agent;
apoptosis inducer;
carcinogenic agent;
mitogen;
plant metabolite;
protein kinase C agonist;
reactive oxygen species generator
danazol
Danazol: A synthetic steroid with antigonadotropic and anti-estrogenic activities that acts as an anterior pituitary suppressant by inhibiting the pituitary output of gonadotropins. It possesses some androgenic properties. Danazol has been used in the treatment of endometriosis and some benign breast disorders.		3.061017beta-hydroxy steroid;
terminal acetylenic compound		anti-estrogen;
estrogen antagonist;
geroprotector
taurolidine
[no description available]		7.4920thiadiazinane
osmium tetroxide
Osmium Tetroxide: (T-4)-Osmium oxide (OsO4). A highly toxic and volatile oxide of osmium used in industry as an oxidizing agent. It is also used as a histological fixative and stain and as a synovectomy agent in arthritic joints. Its vapor can cause eye, skin, and lung damage.. osmium tetroxide : An osmium coordination entity consisting of four oxygen atoms bound to a central osmium atom via covalent double bonds.		1.9810osmium coordination entityfixative;
histological dye;
oxidising agent;
poison
daunorubicin
Daunorubicin: A very toxic anthracycline aminoglycoside antineoplastic isolated from Streptomyces peucetius and others, used in treatment of LEUKEMIA and other NEOPLASMS.. anthracycline : Anthracyclines are polyketides that have a tetrahydronaphthacenedione ring structure attached by a glycosidic linkage to the amino sugar daunosamine.. daunorubicin : A natural product found in Actinomadura roseola.		7.53171aminoglycoside antibiotic;
anthracycline;
p-quinones;
tetracenequinones		antineoplastic agent;
bacterial metabolite
razoxane
Razoxane: An antimitotic agent with immunosuppressive properties.		2.0710N-alkylpiperazine
phenyl acetate
phenyl acetate: The ester formed between phenol and acetic acid. Don't confuse with phenylacetic acid derivatives listed under PHENYLACETATES.. phenyl acetate : An acetate ester obtained by the formal condensation of phenol with acetic acid.		4.1231benzenes;
phenyl acetates
4-methoxyamphetamine
4-methoxyamphetamine: para-methoxy derivative to amphetamine with hallucinogenic properties; minor descriptor (75-86); on line & INDEX MEDICUS search AMPHETAMINES (75-86); RN given refers to parent compound without isomeric designation		2.3920
transferrin
Transferrin: An iron-binding beta1-globulin that is synthesized in the LIVER and secreted into the blood. It plays a central role in the transport of IRON throughout the circulation. A variety of transferrin isoforms exist in humans, including some that are considered markers for specific disease states.		3.1450
fanft
FANFT: A potent nitrofuran derivative tumor initiator. It causes bladder tumors in all animals studied and is mutagenic to many bacteria.		1.9610
glutamic acid
Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.. glutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2.		2.0210glutamic acid;
glutamine family amino acid;
L-alpha-amino acid;
proteinogenic amino acid		Escherichia coli metabolite;
ferroptosis inducer;
micronutrient;
mouse metabolite;
neurotransmitter;
nutraceutical
glucaric acid
Glucaric Acid: A sugar acid derived from D-glucose in which both the aldehydic carbon atom and the carbon atom bearing the primary hydroxyl group are oxidized to carboxylic acid groups.. D-glucaric acid : The D-enantiomer of glucaric acid.. glucaric acid : A hexaric acid derived by oxidation of sugar such as glucose with nitric acid.		5.3322glucaric acidantineoplastic agent
alovudine
[no description available]		4.4322pyrimidine 2',3'-dideoxyribonucleoside
sodium azide
Sodium Azide: A cytochrome oxidase inhibitor which is a nitridizing agent and an inhibitor of terminal oxidation. (From Merck Index, 12th ed). sodium azide : The sodium salt of hydrogen azide (hydrazoic acid).		1.9910inorganic sodium saltantibacterial agent;
explosive;
mitochondrial respiratory-chain inhibitor;
mutagen
azides
Azides: Organic or inorganic compounds that contain the -N3 group.. azide : Any nitrogen molecular entity containing the group -N3.		2.7430pseudohalide anionmitochondrial respiratory-chain inhibitor
adenosine diphosphate ribose
Adenosine Diphosphate Ribose: An ester formed between the aldehydic carbon of RIBOSE and the terminal phosphate of ADENOSINE DIPHOSPHATE. It is produced by the hydrolysis of nicotinamide-adenine dinucleotide (NAD) by a variety of enzymes, some of which transfer an ADP-ribosyl group to target proteins.		2.610ADP-sugarEscherichia coli metabolite;
mouse metabolite
gallium citrate
[no description available]		2.0510
prednimustine
Prednimustine: Ester of CHLORAMBUCIL and PREDNISOLONE used as a combination alkylating agent and synthetic steroid to treat various leukemias and other neoplasms. It causes gastrointestinal and bone marrow toxicity.		6.3671corticosteroid hormone
zidovudine
Zidovudine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia.. zidovudine : A pyrimidine 2',3'-dideoxyribonucleoside compound having a 3'-azido substituent and thymine as the nucleobase.		8.5120azide;
pyrimidine 2',3'-dideoxyribonucleoside		antimetabolite;
antiviral drug;
HIV-1 reverse transcriptase inhibitor
tobramycin
Tobramycin: An aminoglycoside, broad-spectrum antibiotic produced by Streptomyces tenebrarius. It is effective against gram-negative bacteria, especially the PSEUDOMONAS species. It is a 10% component of the antibiotic complex, NEBRAMYCIN, produced by the same species.. tobramycin : A amino cyclitol glycoside that is kanamycin B lacking the 3-hydroxy substituent from the 2,6-diaminoglucose ring.		7.6830amino cyclitol glycosideantibacterial agent;
antimicrobial agent;
toxin
paclitaxel
Taxus: Genus of coniferous yew trees or shrubs, several species of which have medicinal uses. Notable is the Pacific yew, Taxus brevifolia, which is used to make the anti-neoplastic drug taxol (PACLITAXEL).		32.154,2411,818taxane diterpenoid;
tetracyclic diterpenoid		antineoplastic agent;
human metabolite;
metabolite;
microtubule-stabilising agent
etoposide
[no description available]		28.032,018697beta-D-glucoside;
furonaphthodioxole;
organic heterotetracyclic compound		antineoplastic agent;
DNA synthesis inhibitor
substance p
[no description available]		2.0810peptideneurokinin-1 receptor agonist;
neurotransmitter;
vasodilator agent
ribavirin
Rebetron: Rebetron is tradename		9.9211-ribosyltriazole;
aromatic amide;
monocarboxylic acid amide;
primary carboxamide		anticoronaviral agent;
antiinfective agent;
antimetabolite;
antiviral agent;
EC 2.7.7.49 (RNA-directed DNA polymerase) inhibitor
amikacin
Amikacin: A broad-spectrum antibiotic derived from KANAMYCIN. It is reno- and oto-toxic like the other aminoglycoside antibiotics.. amikacin : An amino cyclitol glycoside that is kanamycin A acylated at the N-1 position by a 4-amino-2-hydroxybutyryl group.		2.4520alpha-D-glucoside;
amino cyclitol glycoside;
aminoglycoside;
carboxamide		antibacterial drug;
antimicrobial agent;
nephrotoxin
phorbol 12,13-dibutyrate
Phorbol 12,13-Dibutyrate: A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.		1.9810butyrate ester;
phorbol ester;
tertiary alpha-hydroxy ketone
bezafibrate
[no description available]		2.1110aromatic ether;
monocarboxylic acid amide;
monocarboxylic acid;
monochlorobenzenes		antilipemic drug;
environmental contaminant;
geroprotector;
xenobiotic
nimustine
Nimustine: Antineoplastic agent especially effective against malignant brain tumors. The resistance which brain tumor cells acquire to the initial effectiveness of this drug can be partially overcome by the simultaneous use of membrane-modifying agents such as reserpine, calcium antagonists such as nicardipine or verapamil, or the calmodulin inhibitor, trifluoperazine. The drug has also been used in combination with other antineoplastic agents or with radiotherapy for the treatment of various neoplasms.. nimustine : An organochlorine compound that is urea in which the two hydrogens on one of the amino groups are replaced by nitroso and 2-chloroethyl groups and one hydrogen from the other amino group is replaced by a 4-amino-2-methylpyrimidin-5-ylmethyl] group. An antineoplastic agent especially effective against malignant brain tumors.		5.82122aminopyrimidine;
N-nitrosoureas;
organochlorine compound		alkylating agent;
antineoplastic agent
lonidamine
lonidamine: structure. lonidamine : A member of the class of indazoles that is 1H-indazole that is substituted at positions 1 and 3 by 2,4-dichlorobenzyl and carboxy groups, respectively.		3.7721dichlorobenzene;
indazoles;
monocarboxylic acid		antineoplastic agent;
antispermatogenic agent;
EC 2.7.1.1 (hexokinase) inhibitor;
geroprotector
ng-nitroarginine methyl ester
NG-Nitroarginine Methyl Ester: A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension.		2.1310alpha-amino acid ester;
L-arginine derivative;
methyl ester;
N-nitro compound		EC 1.14.13.39 (nitric oxide synthase) inhibitor
pirfenidone
pirfenidone : A pyridone that is 2-pyridone substituted at positions 1 and 5 by phenyl and methyl groups respectively. An anti-inflammatory drug used for the treatment of idiopathic pulmonary fibrosis.		2.9330pyridoneantipyretic;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug
vindesine
Vindesine: Vinblastine derivative with antineoplastic activity against CANCER. Major side effects are myelosuppression and neurotoxicity. Vindesine is used extensively in chemotherapy protocols (ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS).		13.765219methyl ester;
organic heteropentacyclic compound;
organic heterotetracyclic compound;
primary carboxamide;
tertiary alcohol;
tertiary amino compound;
vinca alkaloid		antineoplastic agent
epirubicin
Epirubicin: An anthracycline which is the 4'-epi-isomer of doxorubicin. The compound exerts its antitumor effects by interference with the synthesis and function of DNA.		19.99257112aminoglycoside;
anthracycline antibiotic;
anthracycline;
deoxy hexoside;
monosaccharide derivative;
p-quinones;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		antimicrobial agent;
antineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor
diaziquone
diaziquone: RN given refers to parent cpd. diaziquone : A 1,4-benzoquinone that is substituted at positions 2 and 5 have been replaced by aziridin-1-yl groups and at positions 3 and 6 by (ethoxycarbonyl)amino groups.		4.83401,4-benzoquinones;
aziridines;
carbamate ester;
enamine		alkylating agent;
antineoplastic agent
enkephalin, methionine
Enkephalin, Methionine: One of the endogenous pentapeptides with morphine-like activity. It differs from LEU-ENKEPHALIN by the amino acid METHIONINE in position 5. Its first four amino acid sequence is identical to the tetrapeptide sequence at the N-terminal of BETA-ENDORPHIN.		2.4720
idarubicin
Idarubicin: An orally administered anthracycline antineoplastic. The compound has shown activity against BREAST NEOPLASMS; LYMPHOMA; and LEUKEMIA.		9.84127anthracycline antibiotic;
deoxy hexoside;
monosaccharide derivative
propiconazole
Orbit: Bony cavity that holds the eyeball and its associated tissues and appendages.		4.6580conazole fungicide;
cyclic ketal;
dichlorobenzene;
triazole fungicide;
triazoles		antifungal agrochemical;
EC 1.14.13.70 (sterol 14alpha-demethylase) inhibitor;
environmental contaminant;
xenobiotic
piperacillin
Piperacillin: Semisynthetic, broad-spectrum, AMPICILLIN derived ureidopenicillin antibiotic proposed for PSEUDOMONAS infections. It is also used in combination with other antibiotics.. piperacillin : A penicillin in which the substituent at position 6 of the penam ring is a 2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carboxamido]-2-phenylacetamido group.		2.2510penicillin allergen;
penicillin		antibacterial drug
moxalactam
Moxalactam: Broad- spectrum beta-lactam antibiotic similar in structure to the CEPHALOSPORINS except for the substitution of an oxaazabicyclo moiety for the thiaazabicyclo moiety of certain CEPHALOSPORINS. It has been proposed especially for the meningitides because it passes the blood-brain barrier and for anaerobic infections.. moxalactam : A broad-spectrum oxacephem antibiotic in which the oxazine ring is substituted with a tetrazolylthiomethyl group and the azetidinone ring carries methoxy and 2-carboxy-2-(4-hydroxyphenyl)acetamido substituents.		1.9710cephalosporin;
oxacephem		antibacterial drug
amonafide
xanafide: salt formulation of amonafide; DNA-intercalating agent and topoisomerase II inhibitor		3.3811isoquinolines
pimonidazole
pimonidazole: structure given in first source		2.4620
pravastatin
Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES).. pravastatin : A carboxylic ester resulting from the formal condensation of (S)-2-methylbutyric acid with the hydroxy group adjacent to the ring junction of (3R,5R)-7-[(1S,2S,6S,8S,8aR)-6,8-dihydroxy-2-methyl-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid. Derived from microbial transformation of mevastatin, pravastatin is a reversible inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA). The sodium salt is used for lowering cholesterol and preventing cardiovascular disease. It is one of the lower potency statins, but has the advantage of fewer side effects compared with lovastatin and simvastatin.		5.06313-hydroxy carboxylic acid;
carbobicyclic compound;
carboxylic ester;
hydroxy monocarboxylic acid;
secondary alcohol;
statin (semi-synthetic)		anticholesteremic drug;
environmental contaminant;
metabolite;
xenobiotic
cabergoline
Cabergoline: An ergoline derivative and dopamine D2-agonist that inhibits PROLACTIN secretion. It is used in the management of HYPERPROLACTINEMIA, and to suppress lactation following childbirth for medical reasons. Cabergoline is also used in the management of PARKINSON DISEASE.. cabergoline : An N-acylurea that is (8R)-ergoline-8-carboxamide in which the hydrogen attached to the piperidine nitrogen (position 6) is substituted by an allyl group and the hydrogens attached to the carboxamide nitrogen are substituted by a 3-(dimethylamino)propyl group and an N-ethylcarbamoyl group. A dopamine D2 receptor agonist, cabergoline is used in the management of Parkinson's disease and of disorders associated with hyperprolactinaemia.		6.9910N-acylureaantineoplastic agent;
antiparkinson drug;
dopamine agonist
raloxifene hydrochloride
Raloxifene Hydrochloride: A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.. raloxifene hydrochloride : A hydrochloride salt resulting from the reaction of equimolar amounts of raloxifene and hydrogen chloride.		2.0510hydrochloridebone density conservation agent;
estrogen antagonist;
estrogen receptor modulator
itraconazole
Itraconazole: A triazole antifungal agent that inhibits cytochrome P-450-dependent enzymes required for ERGOSTEROL synthesis.. itraconazole : An N-arylpiperazine that is cis-ketoconazole in which the imidazol-1-yl group is replaced by a 1,2,4-triazol-1-yl group and in which the actyl group attached to the piperazine moiety is replaced by a p-[(+-)1-sec-butyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]phenyl group. A potent P-glycoprotein and CYP3A4 inhibitor, it is used as an antifungal drug for the treatment of various fungal infections, including aspergillosis, blastomycosis, candidiasis, chromoblastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, and sporotrichosis.		4.4241aromatic ether;
conazole antifungal drug;
cyclic ketal;
dichlorobenzene;
dioxolane;
N-arylpiperazine;
triazole antifungal drug;
triazoles		EC 3.6.3.44 (xenobiotic-transporting ATPase) inhibitor;
Hedgehog signaling pathway inhibitor;
P450 inhibitor
brequinar
brequinar : A quinolinemonocarboxylic acid that is quinoline substituted by 2'-fluoro[1,1'-biphenyl]-4-yl, methyl, carboxy and fluoro groups at positions 2, 3, 4, and 6, respectively. It is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. The compound exhibits antineoplastic and antiviral properties.		2.4110biphenyls;
monocarboxylic acid;
monofluorobenzenes;
quinolinemonocarboxylic acid		anticoronaviral agent;
antimetabolite;
antineoplastic agent;
antiviral agent;
EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor;
immunosuppressive agent;
pyrimidine synthesis inhibitor
imiquimod
Imiquimod: A topically-applied aminoquinoline immune modulator that induces interferon production. It is used in the treatment of external genital and perianal warts, superficial CARCINOMA, BASAL CELL; and ACTINIC KERATOSIS.. imiquimod : An imidazoquinoline fused [4,5-c] carrying isobutyl and amino substituents at N-1 and C-4 respectively. A prescription medication, it acts as an immune response modifier and is used to treat genital warts, superficial basal cell carcinoma, and actinic keratosis.		2.0110imidazoquinolineantineoplastic agent;
interferon inducer
pemirolast
pemirolast: RN from Toxlit; structure given in first source; antiallergic drug		3.8421pyridopyrimidine
piroxantrone
[no description available]		3.3711
aromasil
[no description available]		3.211017-oxo steroid;
3-oxo-Delta(1),Delta(4)-steroid		antineoplastic agent;
EC 1.14.14.14 (aromatase) inhibitor;
environmental contaminant;
xenobiotic
zileuton
[no description available]		5.78221-benzothiophenes;
ureas		anti-asthmatic drug;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor;
ferroptosis inhibitor;
leukotriene antagonist;
non-steroidal anti-inflammatory drug
cidofovir anhydrous
Cidofovir: An acyclic nucleoside phosphonate that acts as a competitive inhibitor of viral DNA polymerases. It is used in the treatment of RETINITIS caused by CYTOMEGALOVIRUS INFECTIONS and may also be useful for treating HERPESVIRUS INFECTIONS.. cidofovir anhydrous : Cytosine substituted at the 1 position by a 3-hydroxy-2-(phosphonomethoxy)propyl group (S configuration). A nucleoside analogue, it is an injectable antiviral used for the treatment of cytomegalovirus (CMV) retinitis in AIDS patients.		3.5111phosphonic acids;
pyrimidone		anti-HIV agent;
antineoplastic agent;
antiviral drug;
photosensitizing agent
mibefradil
Mibefradil: A benzimidazoyl-substituted tetraline that selectively binds and inhibits CALCIUM CHANNELS, T-TYPE.		2.1310tetralinsT-type calcium channel blocker
topotecan
Topotecan: An antineoplastic agent used to treat ovarian cancer. It works by inhibiting DNA TOPOISOMERASES, TYPE I.. topotecan : A pyranoindolizinoquinoline used as an antineoplastic agent. It is a derivative of camptothecin and works by binding to the topoisomerase I-DNA complex and preventing religation of these 328 single strand breaks.		19.3720177pyranoindolizinoquinolineantineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor
gemcitabine
gemcitabine : A 2'-deoxycytidine having geminal fluoro substituents in the 2'-position. An inhibitor of ribonucleotide reductase, gemcitabine is used in the treatment of various carcinomas, particularly non-small cell lung cancer, pancreatic cancer, bladder cancer and breast cancer.		26.37930404organofluorine compound;
pyrimidine 2'-deoxyribonucleoside		antimetabolite;
antineoplastic agent;
antiviral drug;
DNA synthesis inhibitor;
EC 1.17.4.1 (ribonucleoside-diphosphate reductase) inhibitor;
environmental contaminant;
immunosuppressive agent;
photosensitizing agent;
prodrug;
radiosensitizing agent;
xenobiotic
temoporfin
temoporfin: used as PHOTOCHEMOTHERAPY		7.1710
atorvastatin
[no description available]		7.0710aromatic amide;
dihydroxy monocarboxylic acid;
monofluorobenzenes;
pyrroles;
statin (synthetic)		environmental contaminant;
xenobiotic
irinotecan
[no description available]		19.7320592carbamate ester;
delta-lactone;
N-acylpiperidine;
pyranoindolizinoquinoline;
ring assembly;
tertiary alcohol;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
prodrug
ibandronic acid
Ibandronic Acid: Aminobisphosphonate that is a potent inhibitor of BONE RESORPTION. It is used in the treatment of HYPERCALCEMIA associated with malignancy, for the prevention of fracture and bone complications in patients with breast cancer and bone metastases, and for the treatment and prevention of POSTMENOPAUSAL OSTEOPOROSIS.		2.0210
3-iodobenzylguanidine
3-Iodobenzylguanidine: A guanidine analog with specific affinity for tissues of the sympathetic nervous system and related tumors. The radiolabeled forms are used as antineoplastic agents and radioactive imaging agents. (Merck Index, 12th ed) MIBG serves as a neuron-blocking agent which has a strong affinity for, and retention in, the adrenal medulla and also inhibits ADP-ribosyltransferase.		8.46105organoiodine compound
capecitabine
Capecitabine: A deoxycytidine derivative and fluorouracil PRODRUG that is used as an ANTINEOPLASTIC ANTIMETABOLITE in the treatment of COLON CANCER; BREAST CANCER and GASTRIC CANCER.. capecitabine : A carbamate ester that is cytidine in which the hydrogen at position 5 is replaced by fluorine and in which the amino group attached to position 4 is converted into its N-(penyloxy)carbonyl derivative. Capecitabine is a antineoplastic agent used in the treatment of cancers.		12.73612carbamate ester;
cytidines;
organofluorine compound		antimetabolite;
antineoplastic agent;
prodrug
adenosine
quinquefolan B: isolated from roots of Panax quinquefolium L.; RN not in Chemline 10/87; RN from Toxlit		2.4420adenosines;
purines D-ribonucleoside		analgesic;
anti-arrhythmia drug;
fundamental metabolite;
human metabolite;
vasodilator agent
gallium nitrate
gallium nitrate: RN given refers to parent cpd		3.9920
ruthenium chloride (rucl3)
ruthenium chloride: RN given refers to unlabeled cpd		2.3110
benzylaminopurine
benzylaminopurine: a plant growth regulator. N-benzyladenine : A member of the class of 6-aminopurines that is adenine in which one of the hydrogens of the amino group is replaced by a benzyl group.		7.06106-aminopurinescytokinin;
plant metabolite
carbogen
carbogen: mixture of 95% O2 & 5% CO2		4.0831
efavirenz
efavirenz: HIV-1 reverse transcriptase inhibitor. efavirenz : 1,4-Dihydro-2H-3,1-benzoxazin-2-one substituted at the 4 position by cyclopropylethynyl and trifluoromethyl groups (S configuration) and at the 6 position by chlorine. A non-nucleoside reverse transcriptase inhibitor with activity against HIV, it is used with other antiretrovirals for combination therapy of HIV infection.		2.0210acetylenic compound;
benzoxazine;
cyclopropanes;
organochlorine compound;
organofluorine compound		antiviral drug;
HIV-1 reverse transcriptase inhibitor
nelfinavir
Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children.. nelfinavir : An aryl sulfide that is used (as its mesylate salt) for treatment of HIV and also exhibits some anticancer properties.		2.4110aryl sulfide;
benzamides;
organic heterobicyclic compound;
phenols;
secondary alcohol;
tertiary amino compound		antineoplastic agent;
HIV protease inhibitor
glucose, (beta-d)-isomer
beta-D-glucose : D-Glucopyranose with beta configuration at the anomeric centre.. (1->4)-beta-D-glucan : A beta-D-glucan in which the glucose units are connected by (1->4) linkages.. (1->3)-beta-D-glucan : A beta-D-glucan in which the glucose units are connected by (1->3) linkages.		2.1510D-glucopyranoseepitope;
mouse metabolite
thiazolyl blue
thiazolyl blue: RN & II refers to bromide. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide : The bromide salt of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium.		3.89120organic bromide saltcolorimetric reagent;
dye
thymidine 5'-triphosphate
thymidine 5'-triphosphate: RN given refers to parent cpd. dTTP : A thymidine phosphate having a triphosphate group at the 5'-position.		1.9810pyrimidine 2'-deoxyribonucleoside 5'-triphosphate;
thymidine phosphate		Escherichia coli metabolite;
mouse metabolite
baicalin
[no description available]		4.6111dihydroxyflavone;
glucosiduronic acid;
glycosyloxyflavone;
monosaccharide derivative		antiatherosclerotic agent;
antibacterial agent;
anticoronaviral agent;
antineoplastic agent;
antioxidant;
cardioprotective agent;
EC 2.7.7.48 (RNA-directed RNA polymerase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
ferroptosis inhibitor;
neuroprotective agent;
non-steroidal anti-inflammatory drug;
plant metabolite;
prodrug
plerixafor
plerixafor: a bicyclam derivate, highly potent & selective inhibitor of HIV-1 & HIV-2. plerixafor : An azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma.		7.7930azacycloalkane;
azamacrocycle;
benzenes;
crown amine;
secondary amino compound;
tertiary amino compound		anti-HIV agent;
antineoplastic agent;
C-X-C chemokine receptor type 4 antagonist;
immunological adjuvant
amprenavir
[no description available]		2.0210carbamate ester;
sulfonamide;
tetrahydrofuryl ester		antiviral drug;
HIV protease inhibitor
5-methylcytosine
5-Methylcytosine: A methylated nucleotide base found in eukaryotic DNA. In ANIMALS, the DNA METHYLATION of CYTOSINE to form 5-methylcytosine is found primarily in the palindromic sequence CpG. In PLANTS, the methylated sequence is CpNpGp, where N can be any base.. 5-methylcytosine : A pyrimidine that is a derivative of cytosine, having a methyl group at the 5-position.		2.2510methylcytosine;
pyrimidines		human metabolite
2'-deoxycytidine 5'-triphosphate
2'-deoxycytidine 5'-triphosphate: RN given refers to unlabeled parent cpd		2.05102'-deoxycytidine phosphate;
pyrimidine 2'-deoxyribonucleoside 5'-triphosphate		Escherichia coli metabolite;
human metabolite;
mouse metabolite
1,2-distearoyllecithin
[no description available]		2.4820
lissamine rhodamine b
lissamine rhodamine B: RN given refers to parent cpd; Lissamine Rhodamine B refers to Na salt		2.0410
glutathione disulfide
Glutathione Disulfide: A GLUTATHIONE dimer formed by a disulfide bond between the cysteine sulfhydryl side chains during the course of being oxidized.		2.4220glutathione derivative;
organic disulfide		Escherichia coli metabolite;
mouse metabolite
iopamidol
Iopamidol: A non-ionic, water-soluble contrast agent which is used in myelography, arthrography, nephroangiography, arteriography, and other radiological procedures.. iopamidol : A benzenedicarboxamide compound having N-substituted carbamoyl groups at the 1- and 3-positions, iodo substituents at the 2-, 4- and 6-positions and a (2S)-2-hydroxypropanamido group at the 5-position.		2.0510benzenedicarboxamide;
organoiodine compound;
pentol		environmental contaminant;
radioopaque medium;
xenobiotic
cephalosporin c
cephalosporin C: RN given refers to parent cpd; structure in Merck, 9th ed, #1937. cephalosporin C : A cephalosporin antibiotic carrying a 3-acetoxymethyl substituent and a 6-oxo-N(6)-L-lysino group at position 7.		2.1110cephalosporinfungal metabolite
2,2'-dithiodiethanesulfonic acid
[no description available]		2.0110
dicarbine
dicarbine: minor descriptor (77-84); on-line & Index Medicus search CARBOLINES (77-84); RN given refers to parent cpd without isomeric designation		1.9810
trofosfamide
trofosfamide: cyclophosphamide analog; structure		5.5732ifosfamides
tretoquinol
Tretoquinol: An adrenergic beta-agonist used as a bronchodilator agent in asthma therapy.		3.1610isoquinolines
emitefur
Emitefur: structure given in first source		3.0910
goralatide
goralatide: from fetal calf bone marrow; exerts a high inhibitory activity on the proliferation of hematopoietic pluripotent stem cells. goralatide : A tetrapeptide that is Ser-Asp-Lys-Pro in which the N-terminal amino group carries an acetyl group. It is selective inhibitor of primitive haematopoietic cell proliferation and exhibits anti-inflammatory, anti-fibrotic, and pro-angiogenic properties.		8.7821oligopeptide;
tetrapeptide		anti-inflammatory agent;
pro-angiogenic agent
boron nitride
[no description available]		2.1310nitride
iridium radioisotopes
Iridium Radioisotopes: Unstable isotopes of iridium that decay or disintegrate emitting radiation. Ir atoms with atomic weights 182-190, 192, and 194-198 are radioactive iridium isotopes.		5.3872
2-methoxyestradiol
2-methoxy-17beta-estradiol : A 17beta-hydroxy steroid, being 17beta-estradiol methoxylated at C-2.		2.462017beta-hydroxy steroid;
3-hydroxy steroid		angiogenesis modulating agent;
antimitotic;
antineoplastic agent;
human metabolite;
metabolite;
mouse metabolite
naphthalimides
Naphthalimides: Compounds with three fused rings that appear like a naphthalene fused to piperidone or like a benz(de)isoquinoline-1,3-dione (not to be confused with BENZYLISOQUINOLINES which have a methyl separating the naphthyl from the benzyl rings). Members are CYTOTOXINS.		3.3811
bromosuccinimide
Bromosuccinimide: A brominating agent that replaces hydrogen atoms in benzylic or allylic positions. It is used in the oxidation of secondary alcohols to ketones and in controlled low-energy brominations. (From Miall's Dictionary of Chemistry, 5th ed; Hawley's Condensed Chemical Dictionary, 12th ed,).		2.1110dicarboximide;
organobromine compound;
pyrrolidinone		reagent
triazoles
Triazoles: Heterocyclic compounds containing a five-membered ring with two carbon atoms and three nitrogen atoms with the molecular formula C2H3N3.. triazoles : An azole in which the five-membered heterocyclic aromatic skeleton contains three N atoms and two C atoms.		6.841221,2,3-triazole
isocoumarins
Isocoumarins: Compounds that differ from COUMARINS in having the positions of the ring and ketone oxygens reversed so the keto oxygen is at the 1-position of the molecule.. isocoumarin : The simplest member of the class of isocoumarins that is 1H-isochromene which is substituted by an oxo group at position 1.		2.4320isocoumarins
fluorodeoxyglucose f18
Fluorodeoxyglucose F18: The compound is given by intravenous injection to do POSITRON-EMISSION TOMOGRAPHY for the assessment of cerebral and myocardial glucose metabolism in various physiological or pathological states including stroke and myocardial ischemia. It is also employed for the detection of malignant tumors including those of the brain, liver, and thyroid gland. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1162)		13.9161202-deoxy-2-((18)F)fluoro-D-glucose;
2-deoxy-2-fluoro-aldehydo-D-glucose
zoledronic acid
Zoledronic Acid: An imidobisphosphonate inhibitor of BONE RESORPTION that is used for the treatment of malignancy-related HYPERCALCEMIA; OSTEITIS DEFORMANS; and OSTEOPOROSIS.. zoledronic acid : An imidazole compound having a 2,2-bis(phosphono)-2-hydroxyethane-1-yl substituent at the 1-position.		6.77721,1-bis(phosphonic acid);
imidazoles		bone density conservation agent
5-hydroxymethylcytosine
5-(hydroxymethyl)cytosine : A nucleobase analogue that is cytosine in which the hydrogen at position 5 is replaced by a hydroxymethyl group.		2.2510aminopyrimidine;
aromatic primary alcohol;
nucleobase analogue;
pyrimidone		human metabolite;
mouse metabolite
enrofloxacin
Enrofloxacin: A fluoroquinolone antibacterial and antimycoplasma agent that is used in veterinary practice.. enrofloxacin : A quinolinemonocarboxylic acid that is 1,4-dihydroquinoline-3-carboxylic acid substituted by an oxo group at position 4, a fluoro group at position 6, a cyclopropyl group at position 1 and a 4-ethylpiperazin-1-yl group at position 7. It is a veterinary antibacterial agent used for the treatment of pets.		2.1510cyclopropanes;
N-alkylpiperazine;
N-arylpiperazine;
organofluorine compound;
quinolinemonocarboxylic acid;
quinolone		antibacterial agent;
antimicrobial agent;
antineoplastic agent
dapoxetine
[no description available]		4.6111naphthalenes
voriconazole
Voriconazole: A triazole antifungal agent that specifically inhibits STEROL 14-ALPHA-DEMETHYLASE and CYTOCHROME P-450 CYP3A.. voriconazole : A triazole-based antifungal agent used for the treatment of esophageal candidiasis, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp. It is an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4.		5.2431conazole antifungal drug;
difluorobenzene;
pyrimidines;
tertiary alcohol;
triazole antifungal drug		P450 inhibitor
ranimustine
ranimustine: RN given refers to (alpha)-(D)-isomer; structure		7.57266organic molecular entity
dw a 2114r
[no description available]		10.3476platinum coordination entity;
pyrrolidines		antineoplastic agent
7-hydroxystaurosporine
[no description available]		8.4211
nobiletin
nobiletin : A methoxyflavone that is flavone substituted by methoxy groups at positions 5, 6, 7, 8, 3' and 4' respectively.		7.110methoxyflavoneantineoplastic agent;
plant metabolite
leupeptin
[no description available]		210aldehyde;
tripeptide		bacterial metabolite;
calpain inhibitor;
cathepsin B inhibitor;
EC 3.4.21.4 (trypsin) inhibitor;
serine protease inhibitor
picropodophyllin
picropodophyllin: isolated from American May apple (Podophyllum); inhibits IGF-I autophosphorylation without interfering with tyrosine kinase activity. picropodophyllotoxin : An organic heterotetracyclic compound that has a furonaphthodioxole skeleton bearing 3,4,5-trimethoxyphenyl and hydroxy substituents.		3.511furonaphthodioxole;
lignan;
organic heterotetracyclic compound		antineoplastic agent;
insulin-like growth factor receptor 1 antagonist;
plant metabolite;
tyrosine kinase inhibitor
squalamine
squalamine: from dogfish shark Squalus acanthias; structure given in first source		8.821bile acid
3-deazaneplanocin
3-deazaneplanocin: S-adenosylhomocysteine hydrolase antagonist		2.110
corilagin
corilagin: isolated from Geranii herba. corilagin : An ellagitannin with a hexahydroxydiphenoyl group bridging over the 3-O and 6-O of the glucose core.		2.1510ellagitannin;
gallate ester		antihypertensive agent;
antioxidant;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor;
non-steroidal anti-inflammatory drug
bendamustine hydrochloride
[no description available]		6.5244
rosiglitazone
[no description available]		4.3641aminopyridine;
thiazolidinediones		EC 6.2.1.3 (long-chain-fatty-acid--CoA ligase) inhibitor;
ferroptosis inhibitor;
insulin-sensitizing drug
bexarotene
[no description available]		5.754benzoic acids;
naphthalenes;
retinoid		antineoplastic agent
n-acryloyl-tris(hydroxymethyl)aminomethane
N-acryloyl-tris(hydroxymethyl)aminomethane: structure: CH2=CH-CO-NH-C(CH2OH)3		2.0110
nicotine
(S)-nicotine : A 3-(1-methylpyrrolidin-2-yl)pyridine in which the chiral centre has S-configuration. The naturally occurring and most active enantiomer of nicotine, isolated from Nicotiana tabacum.		4.61113-(1-methylpyrrolidin-2-yl)pyridineanxiolytic drug;
biomarker;
immunomodulator;
mitogen;
neurotoxin;
nicotinic acetylcholine receptor agonist;
peripheral nervous system drug;
phytogenic insecticide;
plant metabolite;
psychotropic drug;
teratogenic agent;
xenobiotic
fibrinogen
Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products.. D-iditol : The D-enantiomer of iditol.		2.0210iditolfungal metabolite
methylglucoside
[no description available]		1.9810
fluoromisonidazole
[no description available]		2.0510
lopinavir
[no description available]		4.6111amphetamines;
dicarboxylic acid diamide		anticoronaviral agent;
antiviral drug;
HIV protease inhibitor
glucuronic acid
Glucuronic Acid: A sugar acid formed by the oxidation of the C-6 carbon of GLUCOSE. In addition to being a key intermediate metabolite of the uronic acid pathway, glucuronic acid also plays a role in the detoxification of certain drugs and toxins by conjugating with them to form GLUCURONIDES.. D-glucuronic acid : The D-enantiomer of glucuronic acid.. D-glucopyranuronic acid : A D-glucuronic acid in cyclic pyranose form.		2.7430D-glucuronic acidalgal metabolite
phosphoramide mustard
[no description available]		8.4111nitrogen mustard;
phosphorodiamide
4-hydroxycyclophosphamide
4-hydroxycyclophosphamide: primary activation metabolite of cyclophosphamide; RN given refers to cpd without isomeric designation. 4-hydroxycyclophosphamide : A phosphorodiamide that consists of 2-amino-1,3,2-oxazaphosphinan-4-ol 2-oxide having two 2-chloroethyl groups attached to the exocyclic nitrogen.		9.8842nitrogen mustard;
organochlorine compound;
phosphorodiamide		alkylating agent;
metabolite
combretastatin
combretastatin: cytotoxic principle from South African tree COMBRETUM caffrum; structure given in first source; acts at COLCHICINE site of TUBULIN		2.0110
cobalt
Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis.. cobalt(1+) : A monovalent inorganic cation obtained from cobalt.. cobalt atom : A cobalt group element atom that has atomic number 27.		2.1710cobalt group element atom;
metal allergen		micronutrient
fulvestrant
Fulvestrant: An estradiol derivative and estrogen receptor antagonist that is used for the treatment of estrogen receptor-positive, locally advanced or metastatic breast cancer.. fulvestrant : A 3-hydroxy steroid that is 17beta-estradiol in which the 7alpha hydrogen has been replaced by a nonyl group in which one of the hydrogens of the terminal methyl has been replaced by a (4,4,5,5,5-pentafluoropentyl)sulfinyl group. An estrogen receptor antagonist, it is used in the treatment of breast cancer.		2.071017beta-hydroxy steroid;
3-hydroxy steroid;
organofluorine compound;
sulfoxide		antineoplastic agent;
estrogen antagonist;
estrogen receptor antagonist
mafosfamide
mafosfamide: RN given refers to cis-(+-)-isomer		2.0210
uftoral
UFT(R) drug: a drug containing tegafur and uracil; a biochemical modulator of 5-fluorouracil; used for postoperative chemotherapy of colon cancer; reported to cause severe liver injury; do not confuse with 1-UFT protocol		6.8361
1,2-bis(2-aminophenoxy)ethane-n,n,n',n'-tetraacetic acid
1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid: structure in first source		210polyamino carboxylic acid;
tetracarboxylic acid		chelator
yttrium radioisotopes
Yttrium Radioisotopes: Unstable isotopes of yttrium that decay or disintegrate emitting radiation. Y atoms with atomic weights 82-88 and 90-96 are radioactive yttrium isotopes.		2.4320
fotemustine
fotemustine: structure given in first source. fotemustine : A racemate comprising equimolar amounts of (R)- and (S)-fotemustine. It is an alkylating agent used in the treatment of malignant melanoma.. diethyl (1-{[(2-chloroethyl)(nitroso)carbamoyl]amino}ethyl)phosphonate : A member of the class of N-nitrosoureas that is ethyl diethylphosphonate in the hydrogen at position 1 of the ethyl group attached to the phosphorus has been replaced by a [(2-chloroethyl)(nitroso)carbamoyl]amino group.		4.7350N-nitrosoureas;
organic phosphonate;
organochlorine compound
arginyl-glycyl-aspartic acid
arginyl-glycyl-aspartic acid: amino acid sequence of basic unit of widespread cellular recognition system		2.1510oligopeptide
wr 1065
WR-1065 : An alkanethiol that is the N-3-aminopropyl derivative of cysteamine. Used as the S-phosphorylated prodrug, amifostine, for cytoprotection in cancer chemotherapy and radiotherapy.		5.3953alkanethiol;
diamine		antioxidant;
drug metabolite;
radiation protective agent
vitamin b 6
Vitamin B 6: VITAMIN B 6 refers to several PICOLINES (especially PYRIDOXINE; PYRIDOXAL; & PYRIDOXAMINE) that are efficiently converted by the body to PYRIDOXAL PHOSPHATE which is a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, and aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into PYRIDOXAMINE phosphate. Although pyridoxine and Vitamin B 6 are still frequently used as synonyms, especially by medical researchers, this practice is erroneous and sometimes misleading (EE Snell; Ann NY Acad Sci, vol 585 pg 1, 1990). Most of vitamin B6 is eventually degraded to PYRIDOXIC ACID and excreted in the urine.		2.3110
cremophor el
cremophor EL: solvent for Althesin & Propanidid implicated as possible cause of similar adverse effects polyethoxylated castor oil; RN given refers to cpd with unknown MF; see also records for cremophor & cremophor A		5.4253
1,n(6)-ethenoadenine
1,N(6)-ethenoadenine: biologically active fluorescent derivatives of this cpd potentially valuable in studies concerning interactions between adenine cpds & various enzymes for which they serve as substrates or co-factors; structure		4.6111imidazo[2,1-i]purinemutagen
artesunic acid
[no description available]		3.9530
thiamethoxam
Thiamethoxam: A nitro-oxazine and thiazole derivative that is used as a broad spectrum neonicotinoid insecticide.. thiamethoxam : An oxadiazane that is tetrahydro-N-nitro-4H-1,3,5-oxadiazin-4-imine bearing (2-chloro-1,3-thiazol-5-yl)methyl and methyl substituents at positions 3 and 5 respectively.		4.61111,3-thiazoles;
2-nitroguanidine derivative;
organochlorine compound;
oxadiazane		antifeedant;
carcinogenic agent;
environmental contaminant;
neonicotinoid insectide;
xenobiotic
chlorodiethylenetriamine platinum
chlorodiethylenetriamine platinum: RN given refers to parent cpd; structure		2.0110
marcellomycin
marcellomycin: pyrromycinone glycoside antibiotic isolated from bohemic acid complex; RN given refers to parent cpd(1R-(1alpha,2beta,4beta))-isomer; structure in fourth source		3.0610
procyanidin
Proanthocyanidins: Dimers and oligomers of flavan-3-ol units (CATECHIN analogs) linked mainly through C4 to C8 bonds to leucoanthocyanidins. They are structurally similar to ANTHOCYANINS but are the result of a different fork in biosynthetic pathways.		4.7921proanthocyanidin
fingolimod hydrochloride
Fingolimod Hydrochloride: A sphingosine-derivative and IMMUNOSUPPRESSIVE AGENT that blocks the migration and homing of LYMPHOCYTES to the CENTRAL NERVOUS SYSTEM through its action on SPHINGOSINE 1-PHOSPHATE RECEPTORS. It is used in the treatment of MULTIPLE SCLEROSIS.. fingolimod hydrochloride : The hydrochloride salt of 2-amino-2-[2-(4-octylphenyl) ethyl]-1,3-propanediol (fingolimod).		2.1710hydrochlorideimmunosuppressive agent;
prodrug;
sphingosine-1-phosphate receptor agonist
triptolide
[no description available]		3.0340diterpenoid;
epoxide;
gamma-lactam;
organic heteroheptacyclic compound		antispermatogenic agent;
plant metabolite
ramosetron
[no description available]		10.9433indoles
cobaltiprotoporphyrin
cobaltiprotoporphyrin: RN given refers to cobalt protoporphyrin IX		2.0610
ecteinascidin 743
[no description available]		8.2484acetate ester;
azaspiro compound;
bridged compound;
hemiaminal;
isoquinoline alkaloid;
lactone;
organic heteropolycyclic compound;
organic sulfide;
oxaspiro compound;
polyphenol;
tertiary amino compound		alkylating agent;
angiogenesis modulating agent;
anti-inflammatory agent;
antineoplastic agent;
marine metabolite
1-hexadecyl-2-acetyl-glycero-3-phosphocholine
Platelet Activating Factor: A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION.. 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine : A 2-acetyl-1-alkyl-sn-glycero-3-phosphocholine betaine which has hexadecyl as the alkyl group. PAF is a potent phospholipid activator and mediator of many leukocyte functions, including platelet aggregation, inflammation, and anaphylaxis.		2.25102-acetyl-1-alkyl-sn-glycero-3-phosphocholineantihypertensive agent;
beta-adrenergic antagonist;
bronchoconstrictor agent;
hematologic agent;
vasodilator agent
deoxyglucose
Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity.. deoxyglucose : A deoxyhexose comprising glucose having at least one hydroxy group replaced by hydrogen.		2.9740
anecortave acetate
anecortave acetate: derived from cortisone (11 OH replaced by 9-11 double bond)		2.7330organic molecular entity
monochlorobimane
monochlorobimane: marker for glutathione		1.9810organochlorine compound;
pyrazolopyrazole		fluorochrome
tanshinone
tanshinone: from root of Salvia miltiorrhiza Bunge; RN given refers to tanshinone I; cardioprotective agent and neuroprotective agent		7.1310abietane diterpenoidanticoronaviral agent
wr 33278
WR 33278: symmetrical disulfide of WR-1065		1.9710
fe(ii)-edta
Fe(II)-EDTA: RN given refers to parent cpd		1.9810iron coordination entity
bis-neodecanoato-1,2-diaminocyclohexaneplatinum(ii)
[no description available]		3.0810
marimastat
marimastat: a matrix metalloproteinase inhibitor active in patients with advanced carcinoma of the pancreas, prostate, or ovary. marimastat : A secondary carboxamide resulting from the foraml condensation of the carboxy group of (2R)-2-[(1S)-1-hydroxy-2-(hydroxyamino)-2-oxoethyl]-4-methylpentanoic acid with the alpha-amino group of N,3-dimethyl-L-valinamide.		9.921hydroxamic acid;
secondary carboxamide		antineoplastic agent;
matrix metalloproteinase inhibitor
clofarabine
[no description available]		4.0910adenosines;
organofluorine compound		antimetabolite;
antineoplastic agent
sr 48692
SR 48692: structure in first source; a neurotensin receptor-1 antagonist		3.5311N-acyl-amino acid
tris(2-carboxyethyl)phosphine
tris(2-carboxyethyl)phosphine: water-soluble reagent which irreversibly reduces disulfides to thiols at room temperature & is active below neutral pH; used for quantitation of iodine and iodate. TCEP : A tertiary phosphine in which phosphane is substituted with three 2-carboxyethyl groups. It is a commonly used reducing agent.		2.0810phosphine derivative;
tricarboxylic acid		reducing agent
5-fluorodihydrouracil
5-fluorodihydrouracil: metabolite of 5-fluorouracil; RN given refers to parent cpd		210pyrimidone
efaproxiral
efaproxiral: RN & structure given in first source; allosteric effector of hemoglobin		10.0231
astragaloside a
[no description available]		2.3110
celastrol
[no description available]		7.2110monocarboxylic acid;
pentacyclic triterpenoid		anti-inflammatory drug;
antineoplastic agent;
antioxidant;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
Hsp90 inhibitor;
metabolite
peroxynitrous acid
Peroxynitrous Acid: A potent oxidant synthesized by the cell during its normal metabolism. Peroxynitrite is formed from the reaction of two free radicals, NITRIC OXIDE and the superoxide anion (SUPEROXIDES).		4.6111nitrogen oxoacid
fullerene c60
Fullerenes: A polyhedral CARBON structure composed of around 60-80 carbon atoms in pentagon and hexagon configuration. They are named after Buckminster Fuller because of structural resemblance to geodesic domes. Fullerenes can be made in high temperature such as arc discharge in an inert atmosphere.. fullerene : A compound composed solely of an even number of carbon atoms, which form a cage-like fused-ring polycyclic system with twelve five-membered rings and the rest six-membered rings. The term has been broadened to include any closed cage structure consisting entirely of three-coordinate carbon atoms.		2.1310fullerenegeroprotector
imatinib mesylate
imatinib methanesulfonate : A methanesulfonate (mesylate) salt that is the monomesylate salt of imatinib. Used for treatment of chronic myelogenous leukemia and gastrointestinal stromal tumours.		8.54142methanesulfonate saltanticoronaviral agent;
antineoplastic agent;
apoptosis inducer;
tyrosine kinase inhibitor
gefitinib
[no description available]		19.1813577aromatic ether;
monochlorobenzenes;
monofluorobenzenes;
morpholines;
quinazolines;
secondary amino compound;
tertiary amino compound		antineoplastic agent;
epidermal growth factor receptor antagonist
galactosyl-(1-3)galactose
galactosyl-(1-3)galactose: RN given refers to (alpha-D)-isomer		3.5111O-acyl carbohydrate
angiotensin ii, des-phe(8)-
Ile(5)-angiotensin II (1-7) : An angiotensin compound consisting of the linear heptapeptide sequence L-Asp-L-Arg-L-Val-L-Tyr-L-Ile-L-His-L-Pro.		3.4711amino acid zwitterion;
angiotensin		vasodilator agent
1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone
1-((3,5-dichloro)-2,6-dihydroxy-4-methoxyphenyl)-1-hexanone: structure given in first source. 1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one : A differentiation-inducing factor that is hexaphenone bearing two chloro substituents at positions 3 and 5, two hydroxy substituents at positions 2 and 6 as well as a single methoxy substituent at position 4. A secreted, chlorinated molecule that controls cell fate during development of Dictyostelium cells.		2.0210dichlorobenzene;
differentiation-inducing factor;
monomethoxybenzene;
resorcinols		eukaryotic metabolite;
signalling molecule
vadimezan
vadimezan : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by a 5,6-dimethyl-9-oxoxanthen-4-yl group.		6.9965monocarboxylic acid;
xanthones		antineoplastic agent
lestaurtinib
[no description available]		2.0410indolocarbazole
methotrexate
[no description available]		18.9221271dicarboxylic acid;
monocarboxylic acid amide;
pteridines		abortifacient;
antimetabolite;
antineoplastic agent;
antirheumatic drug;
dermatologic drug;
DNA synthesis inhibitor;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
immunosuppressive agent
platinum(ii) pentamidine
platinum(II) pentamidine: structure given in first source		1.9710
2',2'-difluorodeoxycytidine 5'-triphosphate
[no description available]		2.9610pyrimidone
auranthine
auranthine: identified in extracts of mycelia of most of the nephrotoxic fungi cultured on CDYE both		2.0610benzodiazepine
dexpanthenol
dexpanthenol: The alcohol of pantothenic acid		4.3422amino alcohol;
monocarboxylic acid amide		cholinergic drug;
provitamin
5-ethylamino-9-diethylaminobenzo(a)phenothiazinium
5-ethylamino-9-diethylaminobenzo(a)phenothiazinium: structure in first source; RN refers to the chloride salt		2.4920
abiraterone
[no description available]		2.25103beta-hydroxy-Delta(5)-steroid;
3beta-sterol;
pyridines		antineoplastic agent;
EC 1.14.99.9 (steroid 17alpha-monooxygenase) inhibitor
calcium borate
calcium borate: RN given refers to cpd with MF CaB4O7		4.6111
xylose
xylopyranose: structure in first source		3.821D-xylose
cd 437
CD 437: selective for retinoic acid receptors gamma. CD437 : A naphthoic acid that is 6-phenylnaphthylene-2-carboxyic acid in which the phenyl substituent has been substituted at positions 3 and 4 by adamant-1-yl and hydroxy groups, respectively. It acts as a selective agonist of retinoic acid receptor (RAR)gamma and induces cell cycle arrest and apoptosis in various cancer cells.		210adamantanes;
monocarboxylic acid;
naphthoic acid;
phenols		apoptosis inducer;
retinoic acid receptor gamma agonist
proline
Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.. proline : An alpha-amino acid that is pyrrolidine bearing a carboxy substituent at position 2.		2.0110amino acid zwitterion;
glutamine family amino acid;
L-alpha-amino acid;
proline;
proteinogenic amino acid		algal metabolite;
compatible osmolytes;
Escherichia coli metabolite;
micronutrient;
mouse metabolite;
nutraceutical;
Saccharomyces cerevisiae metabolite
10-propargyl-10-deazaaminopterin
10-propargyl-10-deazaaminopterin: structure in first source. pralatrexate : A pteridine that is the N-4-[1-(2,4-diaminopteridin-6-yl)pent-4-yn-2-yl]benzoyl derivative of L-glutamic acid. Used for treatment of Peripheral T-Cell Lymphoma, an aggressive form of non-Hodgkins lymphoma.		3.8321N-acyl-L-glutamic acid;
pteridines;
terminal acetylenic compound		antimetabolite;
antineoplastic agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
docetaxel anhydrous
Docetaxel: A semisynthetic analog of PACLITAXEL used in the treatment of locally advanced or metastatic BREAST NEOPLASMS and NON-SMALL CELL LUNG CANCER.. docetaxel anhydrous : A tetracyclic diterpenoid that is paclitaxel with the N-benzyloxycarbonyl group replaced by N-tert-butoxycarbonyl, and the acetoxy group at position 10 replaced by a hydroxy group.		24.58674248secondary alpha-hydroxy ketone;
tetracyclic diterpenoid		antimalarial;
antineoplastic agent;
photosensitizing agent
jm 221
JM 221: structure given in first source		2.3920
lonafarnib
lonafarnib: inhibitor of farnesyl protein transferase. lonafarnib : A 4-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamide that has R configuration. It is used as oral farnesyltransferase inhibitor.		10.36224-{2-[4-(3,10-dibromo-8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-yl)piperidin-1-yl]-2-oxoethyl}piperidine-1-carboxamideantineoplastic agent;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor
platinum(ii) 1,2-diaminocyclohexane malonate
platinum(II) 1,2-diaminocyclohexane malonate: RN given refers to (SP-4-2-(trans))-isomer		1.9710
levofloxacin
Levofloxacin: The L-isomer of Ofloxacin.. levofloxacin : An optically active form of ofloxacin having (S)-configuration; an inhibitor of bacterial topoisomerase IV and DNA gyrase.		8.45119-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid;
fluoroquinolone antibiotic;
quinolone antibiotic		antibacterial drug;
DNA synthesis inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
topoisomerase IV inhibitor
dx 8951
[no description available]		2.0310pyranoindolizinoquinoline
1,2-diaminocyclohexyl platinum sulfate
1,2-diaminocyclohexyl platinum sulfate: RN given refers to cpd without isomeric designation		3.4720
canertinib
[no description available]		3.4111monochlorobenzenes;
morpholines;
organofluorine compound;
quinazolines		antineoplastic agent;
tyrosine kinase inhibitor
hydroxyl radical
Hydroxyl Radical: The univalent radical OH. Hydroxyl radical is a potent oxidizing agent.		2.4320oxygen hydride;
oxygen radical;
reactive oxygen species
tipifarnib
[no description available]		2.4320imidazoles;
monochlorobenzenes;
primary amino compound;
quinolone		antineoplastic agent;
apoptosis inducer;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor
atrasentan
Atrasentan: A pyrrolidine and benzodioxole derivative that acts a RECEPTOR, ENDOTHELIN A antagonist. It has therapeutic potential as an antineoplastic agent and for the treatment of DIABETIC NEPHROPATHIES.		8.4311pyrrolidines
tetraammineplatinum(ii)
[no description available]		2.3920
cyc 202
seliciclib : 2,6-Diaminopurine carrying benzylamino, (2R)-1-hydroxybutan-2-yl and isopropyl substituents at C-6, C-2-N and N-9 respectively. It is an experimental drug candidate in the family of pharmacological cyclin-dependent kinase (CDK) inhibitors.		2.47202,6-diaminopurinesantiviral drug;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
ampelopsin
ampelopsin: hepatoprotective agent; isolated from Hovenia dulcis; RN given for (2R-trans)-isomer; structure in first source. (+)-dihydromyricetin : An optically active form of dihydromyricetin having (2R,3R)-configuration.		7.1510dihydromyricetin;
secondary alpha-hydroxy ketone		antineoplastic agent;
antioxidant;
metabolite
methylselenic acid
methylseleninic acid : An organoselenium compound that is seleninic acid in which the hydrogen attached to selenium is replaced by a methyl group.		2.4820one-carbon compound;
organoselenium compound		antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
human xenobiotic metabolite
doranidazole
doranidazole: structure given in first source		3.4211
calcium pyrophosphate
[no description available]		2.3920
technetium tc 99m pentetate
Technetium Tc 99m Pentetate: A technetium imaging agent used in renal scintigraphy, computed tomography, lung ventilation imaging, gastrointestinal scintigraphy, and many other procedures which employ radionuclide imaging agents.		3.6490
aminopterin
Aminopterin: A folic acid derivative used as a rodenticide that has been shown to be teratogenic.		6.8774dicarboxylic acidEC 1.5.1.3 (dihydrofolate reductase) inhibitor;
mutagen
biotin
vitamin B7 : Any member of a group of vitamers that belong to the chemical structural class called biotins that exhibit biological activity against vitamin B7 deficiency. Vitamin B7 deficiency is very rare in individuals who take a normal balanced diet. Foods rich in biotin are egg yolk, liver, cereals, vegetables (spinach, mushrooms) and rice. Symptoms associated with vitamin B7 deficiency include thinning hair, scaly skin rashes around eyes, nose and mouth, and brittle nails. The vitamers include biotin and its ionized and salt forms.		2.0110biotins;
vitamin B7		coenzyme;
cofactor;
Escherichia coli metabolite;
fundamental metabolite;
human metabolite;
mouse metabolite;
nutraceutical;
prosthetic group;
Saccharomyces cerevisiae metabolite
angiotensin ii
Giapreza: injectable form of angiotensin II used to increase blood pressure in adult patients with septic or other distributive shock. Ile(5)-angiotensin II : An angiotensin II that acts on the central nervous system (PDB entry: 1N9V).		710amino acid zwitterion;
angiotensin II		human metabolite
atropine
tropan-3alpha-yl 3-hydroxy-2-phenylpropanoate : A tropane alkaloid that is (1R,5)-8-methyl-8-azabicyclo[3.2.1]octane substituted by a (3-hydroxy-2-phenylpropanoyl)oxy group at position 3.		1.9910
7-hydroxy-5,11-dioxotetranorprostane-1,16-dioic acid
[no description available]		3.4311prostanoid
lignin
Lignin: The most abundant natural aromatic organic polymer found in all vascular plants. Lignin together with cellulose and hemicellulose are the major cell wall components of the fibers of all wood and grass species. Lignin is composed of coniferyl, p-coumaryl, and sinapyl alcohols in varying ratios in different plant species. (From Merck Index, 11th ed). lignin : A polyphenylpropanoid derived from three monolignol monomers: trans-p-coumaryl alcohol, coniferol and trans-sinapyl alcohol. There is extensive cross-linking and no defined primary structure.		2.1510
sb 203580
[no description available]		2.1710imidazoles;
monofluorobenzenes;
pyridines;
sulfoxide		EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector;
Hsp90 inhibitor;
neuroprotective agent
enzastaurin
[no description available]		6.6454indoles;
maleimides
erlotinib hydrochloride
[no description available]		18.599968hydrochloride;
terminal acetylenic compound		antineoplastic agent;
protein kinase inhibitor
organophosphonates
hydrogenphosphite : A divalent inorganic anion resulting from the removal of a proton from two of the hydroxy groups of phosphorous acid.		4.3922divalent inorganic anion;
phosphite ion
indisetron hydrochloride
indisetron hydrochloride: an anti-emetic agent, indisetron hydrochloride was developed in Japan; structure in first source		3.4311
3,7-diazabicyclo(3.3.1)nonane
3,7-diazabicyclo(3.3.1)nonane: 7-aza analog of azabicyclane; structure		2.5220
lapatinib
[no description available]		9.4143furans;
organochlorine compound;
organofluorine compound;
quinazolines		antineoplastic agent;
tyrosine kinase inhibitor
deferasirox
Deferasirox: A triazole and benzoate derivative that acts as a selective iron chelator. It is used in the management of chronic IRON OVERLOAD due to blood transfusion or non-transfusion dependent THALASSEMIA.. deferasirox : A member of the class of triazoles, deferasirox is 1,2,4-triazole substituted by a 4-carboxyphenyl group at position 1 and by 2-hydroxyphenyl groups at positions 3 and 5. An orally active iron chelator, it is used to manage chronic iron overload in patients receiving long-term blood transfusions.		2.1710benzoic acids;
monocarboxylic acid;
phenols;
triazoles		iron chelator
sorafenib
[no description available]		12.22617(trifluoromethyl)benzenes;
aromatic ether;
monochlorobenzenes;
phenylureas;
pyridinecarboxamide		angiogenesis inhibitor;
anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor;
ferroptosis inducer;
tyrosine kinase inhibitor
lenalidomide
[no description available]		9.1373aromatic amine;
dicarboximide;
isoindoles;
piperidones		angiogenesis inhibitor;
antineoplastic agent;
immunomodulator
n-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide
N-(3-chloro-7-indolyl)-1,4-benzenedisulphonamide: structure in first source. indisulam : A chloroindole that is 3-chloro-1H-indole substituted by a [(4-sulfamoylphenyl)sulfonyl]nitrilo group at position 7. It is a carbonic anhydrase inhibitor and a potential anti-cancer agent currently in clinical development.		3.8321chloroindole;
organochlorine compound;
sulfonamide		antineoplastic agent;
EC 4.2.1.1 (carbonic anhydrase) inhibitor
phenoxodiol
phenoxodiol: a synthetic derivative of DAIDZEIN		5.0431
cholic acid
Cholic Acid: A major primary bile acid produced in the liver and usually conjugated with glycine or taurine. It facilitates fat absorption and cholesterol excretion.. cholic acid : A bile acid that is 5beta-cholan-24-oic acid bearing three alpha-hydroxy substituents at position 3, 7 and 12.		7.011012alpha-hydroxy steroid;
3alpha-hydroxy steroid;
7alpha-hydroxy steroid;
bile acid;
C24-steroid;
trihydroxy-5beta-cholanic acid		human metabolite;
mouse metabolite
deoxycholic acid
Deoxycholic Acid: A bile acid formed by bacterial action from cholate. It is usually conjugated with glycine or taurine. Deoxycholic acid acts as a detergent to solubilize fats for intestinal absorption, is reabsorbed itself, and is used as a choleretic and detergent.. deoxycholic acid : A bile acid that is 5beta-cholan-24-oic acid substituted by hydroxy groups at positions 3 and 12 respectively.		2.1510bile acid;
C24-steroid;
dihydroxy-5beta-cholanic acid		human blood serum metabolite
cortisone
[no description available]		2.683011-oxo steroid;
17alpha-hydroxy steroid;
20-oxo steroid;
21-hydroxy steroid;
3-oxo-Delta(4) steroid;
C21-steroid;
glucocorticoid;
primary alpha-hydroxy ketone;
tertiary alpha-hydroxy ketone		human metabolite;
mouse metabolite
estramustine
Estramustine: A nitrogen mustard linked to estradiol, usually as phosphate; used to treat prostatic neoplasms; also has radiation protective properties.. estramustine : A carbamate ester obtained by the formal condensation of the hydroxy group of 17beta-estradiol with the carboxy group of bis(2-chloroethyl)carbamic acid.		11.8271617beta-hydroxy steroid;
carbamate ester;
organochlorine compound		alkylating agent;
antineoplastic agent;
radiation protective agent
elesclomol
[no description available]		3.3110carbohydrazide;
thiocarbonyl compound		antineoplastic agent;
apoptosis inducer
wortmannin
[no description available]		2.110acetate ester;
cyclic ketone;
delta-lactone;
organic heteropentacyclic compound		anticoronaviral agent;
antineoplastic agent;
autophagy inhibitor;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
geroprotector;
Penicillium metabolite;
radiosensitizing agent
menogaril
Menogaril: A semisynthetic anthracycline with the amino sugar on the D ring. It displays broad-spectrum antineoplastic activity against a variety of tumors.		3.3811
nsc 366140
NSC 366140: a 9-methoxypyrazoloacridine; structure given in first source		10.9233
trimethoprim, sulfamethoxazole drug combination
Trimethoprim, Sulfamethoxazole Drug Combination: A drug combination with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.. co-trimoxazole : A two-component mixture comprising trimethoprim and sulfamethoxazole.		2.4120
o-(chloroacetylcarbamoyl)fumagillol
O-(Chloroacetylcarbamoyl)fumagillol: Semisynthetic analog of fumagillin (a cyclohexane-sesquiterpene antibiotic isolated from ASPERGILLUS FUMIGATUS) that inhibits angiogenesis.. O-(chloroacetylcarbamoyl)fumagillol : A carbamate ester that is fumagillol in which the hydroxy group has been converted to the corresponding N-(chloroacetyl)carbamate derivative.		5.4141carbamate ester;
organochlorine compound;
semisynthetic derivative;
sesquiterpenoid;
spiro-epoxide		angiogenesis inhibitor;
antineoplastic agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
methionine aminopeptidase 2 inhibitor;
retinoic acid receptor alpha antagonist
bortezomib
[no description available]		12.082817amino acid amide;
L-phenylalanine derivative;
pyrazines		antineoplastic agent;
antiprotozoal drug;
protease inhibitor;
proteasome inhibitor
ritonavir
Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.. ritonavir : An L-valine derivative that is L-valinamide in which alpha-amino group has been acylated by a [(2-isopropyl-1,3-thiazol-4-yl)methyl]methylcarbamoyl group and in which a hydrogen of the carboxamide amino group has been replaced by a (2R,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl group. A CYP3A inhibitor and antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.		4.95211,3-thiazoles;
carbamate ester;
carboxamide;
L-valine derivative;
ureas		antiviral drug;
environmental contaminant;
HIV protease inhibitor;
xenobiotic
jib-04
JIB-04: structure in first source		2.1510
povidone-iodine
Povidone-Iodine: An iodinated polyvinyl polymer used as topical antiseptic in surgery and for skin and mucous membrane infections, also as aerosol. The iodine may be radiolabeled for research purposes.		4.3822
permanganate
[no description available]		4.6111manganese oxoacid
leupeptins
Leupeptins: A group of acylated oligopeptides produced by Actinomycetes that function as protease inhibitors. They have been known to inhibit to varying degrees trypsin, plasmin, KALLIKREINS, papain and the cathepsins.		210
xr5944
XR5944: structure in first source		7.0210
bradykinin
[no description available]		10.83014oligopeptidehuman blood serum metabolite;
vasodilator agent
carnosine
polaprezinc: stimulates bone growth		7.4920amino acid zwitterion;
dipeptide		anticonvulsant;
antineoplastic agent;
antioxidant;
Daphnia magna metabolite;
geroprotector;
human metabolite;
mouse metabolite;
neuroprotective agent
ouabain
Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.. cardiac glycoside : Steroid lactones containing sugar residues that act on the contractile force of the cardiac muscles.. ouabain : A steroid hormone that is a multi-hydroxylated alpha-L-rhamnosyl cardenoloide. It binds to and inhibits the plasma membrane Na(+)/K(+)-ATPase (sodium pump). It has been isolated naturally from Strophanthus gratus.		1.991011alpha-hydroxy steroid;
14beta-hydroxy steroid;
5beta-hydroxy steroid;
alpha-L-rhamnoside;
cardenolide glycoside;
steroid hormone		anti-arrhythmia drug;
cardiotonic drug;
EC 2.3.3.1 [citrate (Si)-synthase] inhibitor;
EC 3.1.3.41 (4-nitrophenylphosphatase) inhibitor;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor;
EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor;
ion transport inhibitor;
plant metabolite
pentostatin
Pentostatin: A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.. pentostatin : A member of the class of coformycins that is coformycin in which the hydroxy group at position 2' is replaced with a hydrogen. It is a drug used for the treatment of hairy cell leukaemia.		3.411coformycinsantimetabolite;
antineoplastic agent;
Aspergillus metabolite;
bacterial metabolite;
EC 3.5.4.4 (adenosine deaminase) inhibitor
inositol 3-phosphate
inositol 3-phosphate: RN given refers to (myo)-isomer		1.9710
meropenem
Meropenem: A thienamycin derivative antibacterial agent that is more stable to renal dehydropeptidase I than IMIPENEM, but does not need to be given with an enzyme inhibitor such as CILASTATIN. It is used in the treatment of bacterial infections, including infections in immunocompromised patients.. meropenem : A carbapenemcarboxylic acid in which the azetidine and pyrroline rings carry 1-hydroxymethyl and in which the azetidine and pyrroline rings carry 1-hydroxymethyl and 5-(dimethylcarbamoyl)pyrrolidin-3-ylthio substituents respectively.		2.6120alpha,beta-unsaturated monocarboxylic acid;
carbapenemcarboxylic acid;
organic sulfide;
pyrrolidinecarboxamide		antibacterial agent;
antibacterial drug;
drug allergen
abacavir
abacavir: a carbocyclic nucleoside with potent selective anti-HIV activity. abacavir : A 2,6-diaminopurine that is (1S)-cyclopent-2-en-1-ylmethanol in which the pro-R hydrogen at the 4-position is substituted by a 2-amino-6-(cyclopropylamino)-9H-purin-9-yl group. A nucleoside analogue reverse transcriptase inhibitor (NRTI) with antiretroviral activity against HIV, it is used (particularly as the sulfate) with other antiretrovirals in combination therapy of HIV infection.		2.02102,6-diaminopurinesantiviral drug;
drug allergen;
HIV-1 reverse transcriptase inhibitor
sodium arsenite
sodium arsenite : An inoganic sodium salt with formula with formula NaAsO2.		2.0310arsenic molecular entity;
inorganic sodium salt		antibacterial agent;
antifungal agent;
antineoplastic agent;
carcinogenic agent;
herbicide;
insecticide;
rodenticide
betadex
beta-Cyclodextrins: Cyclic GLUCANS consisting of seven (7) glucopyranose units linked by 1,4-glycosidic bonds.		2.7830cyclodextrin
tretinoin
Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).. retinoic acid : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraenoic acid substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified).. all-trans-retinoic acid : A retinoic acid in which all four exocyclic double bonds have E- (trans-) geometry.		7.1963retinoic acid;
vitamin A		anti-inflammatory agent;
antineoplastic agent;
antioxidant;
AP-1 antagonist;
human metabolite;
keratolytic drug;
retinoic acid receptor agonist;
retinoid X receptor agonist;
signalling molecule
resveratrol
trans-resveratrol : A resveratrol in which the double bond has E configuration.		2.0610resveratrolantioxidant;
phytoalexin;
plant metabolite;
quorum sensing inhibitor;
radical scavenger
retinol
Vitamin A: Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of CAROTENOIDS found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products.. vitamin A : Any member of a group of fat-soluble retinoids produced via metabolism of provitamin A carotenoids that exhibit biological activity against vitamin A deficiency. Vitamin A is involved in immune function, vision, reproduction, and cellular communication.. all-trans-retinol : A retinol in which all four exocyclic double bonds have E- (trans-) geometry.. retinol : A retinoid consisting of 3,7-dimethylnona-2,4,6,8-tetraen-1-ol substituted at position 9 by a 2,6,6-trimethylcyclohex-1-en-1-yl group (geometry of the four exocyclic double bonds is not specified).		2.3110retinol;
vitamin A		human metabolite;
mouse metabolite;
plant metabolite
tacrolimus
Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.. tacrolimus (anhydrous) : A macrolide lactam containing a 23-membered lactone ring, originally isolated from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis.		2.0810macrolide lactambacterial metabolite;
immunosuppressive agent
eicosapentaenoic acid
icosapentaenoic acid : Any straight-chain, C20 polyunsaturated fatty acid having five C=C double bonds.. all-cis-5,8,11,14,17-icosapentaenoic acid : An icosapentaenoic acid having five cis-double bonds at positions 5, 8, 11, 14 and 17.		5.3522icosapentaenoic acid;
omega-3 fatty acid		anticholesteremic drug;
antidepressant;
antineoplastic agent;
Daphnia galeata metabolite;
fungal metabolite;
micronutrient;
mouse metabolite;
nutraceutical
zithromax
Azithromycin: A semi-synthetic macrolide antibiotic structurally related to ERYTHROMYCIN. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis.. azithromycin : A macrolide antibiotic useful for the treatment of bacterial infections.		2.3110macrolide antibioticantibacterial drug;
environmental contaminant;
xenobiotic
desoxyepothilone b
desoxyepothilone B: microtubule-targeted antitumor agent; lacking the epoxide of epothilone B; may be equiv to epothilone D. epothilone D : An epithilone that is epithilone C in which the hydrogen at position 13 of the oxacyclohexadec-13-ene-2,6-dione macrocycle has been replaced by a methyl group.		3.4611epothilonemicrotubule-stabilising agent
epothilone b
[no description available]		3.4211epothilone;
epoxide		antineoplastic agent;
apoptosis inducer;
microtubule-stabilising agent
diethylstilbestrol
Diethylstilbestrol: A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed). diethylstilbestrol : An olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups.		2.0110olefinic compound;
polyphenol		antifungal agent;
antineoplastic agent;
autophagy inducer;
calcium channel blocker;
carcinogenic agent;
EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor;
endocrine disruptor;
xenoestrogen
bms 214662
7-cyano-2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-3-(phenylmethyl)-4-(2-thienylsulfonyl)-1H-1,4-benzodiazepine: a farnesyltransferase inhibitor; structure in first source. BMS-214662 : A member of the class of benzodiazepines that is 2,3,4,5-tetrahydro-1H-1,4-benzodiazepine substituted by (1H-imidazol-5-yl)methyl, benzyl, (thiophen-2-yl)sulfonyl, and cyano groups at positions 1, 3R, 4 and 7, respectively. It is a potent inhibitor of farnesyltransferase (IC50 = 1.35nM) which was under clinical development for the treatment of solid tumors.		3.4111benzenes;
benzodiazepine;
imidazoles;
nitrile;
sulfonamide;
thiophenes		antineoplastic agent;
apoptosis inducer;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor
epothilone a
Epothilones: A group of 16-member MACROLIDES which stabilize MICROTUBULES in a manner similar to PACLITAXEL. They were originally found in the myxobacterium Sorangium cellulosum, now renamed to Polyangium (MYXOCOCCALES).		11.03129epothilone;
epoxide		antineoplastic agent;
metabolite;
microtubule-stabilising agent;
tubulin modulator
alitretinoin
Alitretinoin: A retinoid that is used for the treatment of chronic hand ECZEMA unresponsive to topical CORTICOSTEROIDS. It is also used to treat cutaneous lesions associated with AIDS-related KAPOSI SARCOMA.		3.3811retinoic acidantineoplastic agent;
keratolytic drug;
metabolite;
retinoid X receptor agonist
aclarubicin
Aclarubicin: An anthracycline produced by Streptomyces galilaeus. It has potent antineoplastic activity.. aclacinomycin A : An anthracycline antibiotic that is produced by Streptomyces galilaeus and also has potent antineoplastic activity.		1.9810aminoglycoside;
anthracycline;
methyl ester;
phenols;
polyketide;
tetracenequinones;
trisaccharide derivative;
zwitterion		antimicrobial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor
decitabine
[no description available]		9.471472'-deoxyribonucleoside
troxacitabine
troxacitabine: shows good anti-HIV activity without cytotoxicity		2.0310carbohydrate derivative;
nucleobase-containing molecular entity
dactinomycin
Dactinomycin: A compound composed of a two CYCLIC PEPTIDES attached to a phenoxazine that is derived from STREPTOMYCES parvullus. It binds to DNA and inhibits RNA synthesis (transcription), with chain elongation more sensitive than initiation, termination, or release. As a result of impaired mRNA production, protein synthesis also declines after dactinomycin therapy. (From AMA Drug Evaluations Annual, 1993, p2015)		17.12449actinomycinmutagen
tiazofurin
tiazofurin: RN given refers to (beta-D)-isomer; structure given in first source. tiazofurine : A C-glycosyl compound that is 1,3-thiazole-4-carboxamide in which the hydrogen at position 2 has been replaced by a beta-D-ribofuranosyl group. It is metabolised to thiazole-4-carboxamide adenine dinucleotide (TAD), a selective inhibitor of inosine monophosphate dehydrogenase (IMP dehydrogenase).		3.06101,3-thiazoles;
C-glycosyl compound;
monocarboxylic acid amide		antineoplastic agent;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
prodrug
aphidicolin
Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.. aphidicolin : A tetracyclic diterpenoid that has an tetradecahydro-8,11a-methanocyclohepta[a]naphthalene skeleton with two hydroxymethyl substituents at positions 4 and 9, two methyl substituents at positions 4 and 11b and two hydroxy substituents at positions 3 and 9. An antibiotic with antiviral and antimitotical properties. Aphidicolin is a reversible inhibitor of eukaryotic nuclear DNA replication.		2.6830tetracyclic diterpenoidantimicrobial agent;
antimitotic;
antineoplastic agent;
antiviral drug;
apoptosis inducer;
Aspergillus metabolite;
DNA synthesis inhibitor;
EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor;
fungal metabolite
melphalan
Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.. melphalan : A phenylalanine derivative comprising L-phenylalanine having [bis(2-chloroethyl)amino group at the 4-position on the phenyl ring.		17.8820654L-phenylalanine derivative;
nitrogen mustard;
non-proteinogenic L-alpha-amino acid;
organochlorine compound		alkylating agent;
antineoplastic agent;
carcinogenic agent;
drug allergen;
immunosuppressive agent
prinomastat
prinomastat: a diazepine-based hydroxamic acid inhibitor; matrix metalloproteinase (MMP) inhibitor; angiogenesis inhibitor;. prinomastat : A hydroxamic acid that is (3S)-N-hydroxy-2,2-dimethylthiomorpholine-3-carboxamide in which the hydrogen attached to the thiomorpholine nitrogen has been replaced by a [4-(pyridin-4-yloxy)phenyl]sulfonyl group. It is a selective inhibitor with of matrix metalloproteinases (MMPs) 2, 3, 9, 13, and 14.		8.830aromatic ether;
hydroxamic acid;
pyridines;
sulfonamide;
thiomorpholines		antineoplastic agent;
EC 3.4.24.35 (gelatinase B) inhibitor;
matrix metalloproteinase inhibitor
rubitecan
rubitecan: RN refers to (+-)-isomer; anti-HIV agent; DNA Topoisomerases, Type I inhibitor. rubitecan : A pyranoindolizinoquinoline that is camptothecin in which the hydrogen at position 9 has been replaced by a nitro group. It is a prodrug for 9-aminocamptothecin.		2.0110C-nitro compound;
delta-lactone;
pyranoindolizinoquinoline;
semisynthetic derivative;
tertiary alcohol		antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
prodrug
riboflavin
vitamin B2 : Any member of a group of vitamers that belong to the chemical structural class called flavins that exhibit biological activity against vitamin B2 deficiency. Symptoms associated with vitamin B2 deficiency include glossitis, seborrhea, angular stomaitis, cheilosis and photophobia. The vitamers include riboflavin and its phosphate derivatives (and includes their salt, ionised and hydrate forms).		2.3110flavin;
vitamin B2		anti-inflammatory agent;
antioxidant;
cofactor;
Escherichia coli metabolite;
food colouring;
fundamental metabolite;
human urinary metabolite;
mouse metabolite;
photosensitizing agent;
plant metabolite
2,3-bis(bromomethyl)quinoxaline-1,4-dioxide
conoidin A: inhibits the peroxiredoxin TgPrx11; structure in first source		4.6111
sodium bicarbonate
Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions.		2.0410one-carbon compound;
organic sodium salt		antacid;
food anticaking agent
bromochloroacetic acid
Keratins: A class of fibrous proteins or scleroproteins that represents the principal constituent of EPIDERMIS; HAIR; NAILS; horny tissues, and the organic matrix of tooth ENAMEL. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of TYPE I KERATIN and a TYPE II KERATIN, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. alpha-Keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to GENE DUPLICATION.. bromochloroacetic acid : A monocarboxylic acid that is acetic acid in which one of the methyl hydrogens is replaced by bromine while a second is replaced by chlorine. A low-melting (27.5-31.5degreeC), hygroscopic crystalline solid, it can be formed during the disinfection (by chlorination) of water that contains bromide ions and organic matter, so can occur in drinking water as a byproduct of the disinfection process.		5.14802-bromocarboxylic acid;
monocarboxylic acid;
organochlorine compound
isomethyleugenol
Methylation: Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. (From Stedman, 25th ed)		2.1510isomethyleugenol
squalene
Addavax: an oil-water nanoemulsion and adjuvant containing squalene, Tween 80, and sorbitane trioleate		7.0410triterpenehuman metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
stilbenes
Stilbenes: Organic compounds that contain 1,2-diphenylethylene as a functional group.. trans-stilbene : The trans-isomer of stilbene.		7.5994stilbene
picibanil
Picibanil: A lyophilized preparation of a low-virulence strain (SU) of Streptococcus pyogenes (S. hemolyticus), inactivated by heating with penicillin G. It has been proposed as a noncytotoxic antineoplastic agent because of its immune system-stimulating activity.		2.3820penicillinate anion
cannabidiol
Cannabidiol: Compound isolated from Cannabis sativa extract.. cannabidiol : An cannabinoid that is cyclohexene which is substituted by a methyl group at position 1, a 2,6-dihydroxy-4-pentylphenyl group at position 3, and a prop-1-en-2-yl group at position 4.		2.3110olefinic compound;
phytocannabinoid;
resorcinols		antimicrobial agent;
plant metabolite
s 1033
[no description available]		2.110(trifluoromethyl)benzenes;
imidazoles;
pyridines;
pyrimidines;
secondary amino compound;
secondary carboxamide		anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
mitobronitol
Mitobronitol: Brominated analog of MANNITOL which is an antineoplastic agent appearing to act as an alkylating agent.		1.9810alcohol;
organobromine compound
tropisetron
Tropisetron: An indole derivative and 5-HT3 RECEPTOR antagonist that is used for the prevention of nausea and vomiting.. tropisetron : An indolyl carboxylate ester obtained by formal condensation of the carboxy group of indole-3-carboxylic acid with the hydroxy group of tropine.		5.453indolyl carboxylic acid
leuprolide
Leuprolide: A potent synthetic long-acting agonist of GONADOTROPIN-RELEASING HORMONE that regulates the synthesis and release of pituitary gonadotropins, LUTEINIZING HORMONE and FOLLICLE STIMULATING HORMONE.. leuprolide : An oligopeptide comprising pyroglutamyl, histidyl, tryptophyl, seryl, tyrosyl, D-leucyl, leucyl, arginyl, and N-ethylprolinamide residues joined in sequence. It is a synthetic nonapeptide analogue of gonadotropin-releasing hormone, and is used as a subcutaneous hydrogel implant (particularly as the acetate salt) for the treatment of prostate cancer and for the suppression of gonadal sex hormone production in children with central precocious puberty.		4.3541oligopeptideanti-estrogen;
antineoplastic agent;
gonadotropin releasing hormone agonist
fludarabine
[no description available]		6.7783purine nucleoside
propylthiouracil
Propylthiouracil: A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534). 6-propyl-2-thiouracil : A pyrimidinethione consisting of uracil in which the 2-oxo group is substituted by a thio group and the hydrogen at position 6 is substituted by a propyl group.		3.1810pyrimidinethioneantidote to paracetamol poisoning;
antimetabolite;
antioxidant;
antithyroid drug;
carcinogenic agent;
EC 1.14.13.39 (nitric oxide synthase) inhibitor;
hormone antagonist
sesquiterpenes
[no description available]		5.4141
mercaptopurine
Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia.. purine-6-thiol : A thiol that is the tautomer of mercaptopurine.. mercaptopurine : A member of the class of purines that is 6,7-dihydro-1H-purine carrying a thione group at position 6. An adenine analogue, it is used in the treatment of acute lymphocytic leukemia (ALL), chronic myeloid leukemia (CML), Crohn's disease, and ulcerative colitis.		2.4220aryl thiol;
purines;
thiocarbonyl compound		anticoronaviral agent;
antimetabolite;
antineoplastic agent
1-methyltryptophan
1-methyltryptophan: an immunomodulator. 1-methyltryptophan : A tryptophan derivative that is tryptophan carrying a single methyl substituent at position 1 on the indole.		2.2510indolyl carboxylic acid
curcumin
Curcumin: A yellow-orange dye obtained from tumeric, the powdered root of CURCUMA longa. It is used in the preparation of curcuma paper and the detection of boron. Curcumin appears to possess a spectrum of pharmacological properties, due primarily to its inhibitory effects on metabolic enzymes.. curcumin : A beta-diketone that is methane in which two of the hydrogens are substituted by feruloyl groups. A natural dyestuff found in the root of Curcuma longa.		581aromatic ether;
beta-diketone;
diarylheptanoid;
enone;
polyphenol		anti-inflammatory agent;
antifungal agent;
antineoplastic agent;
biological pigment;
contraceptive drug;
dye;
EC 1.1.1.205 (IMP dehydrogenase) inhibitor;
EC 1.1.1.21 (aldehyde reductase) inhibitor;
EC 1.1.1.25 (shikimate dehydrogenase) inhibitor;
EC 1.6.5.2 [NAD(P)H dehydrogenase (quinone)] inhibitor;
EC 1.8.1.9 (thioredoxin reductase) inhibitor;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
EC 3.5.1.98 (histone deacetylase) inhibitor;
flavouring agent;
food colouring;
geroprotector;
hepatoprotective agent;
immunomodulator;
iron chelator;
ligand;
lipoxygenase inhibitor;
metabolite;
neuroprotective agent;
nutraceutical;
radical scavenger
ptc-209
PTC-209: inhibits BMI-1 protein; structure in first source		2.1110
cinnarizine
Cinnarizine: A piperazine derivative having histamine H1-receptor and calcium-channel blocking activity with vasodilating and antiemetic properties but it induces PARKINSONIAN DISORDERS.		3.3611diarylmethane;
N-alkylpiperazine;
olefinic compound		anti-allergic agent;
antiemetic;
calcium channel blocker;
geroprotector;
H1-receptor antagonist;
histamine antagonist;
muscarinic antagonist
sulindac
Sulindac: A sulfinylindene derivative prodrug whose sulfinyl moiety is converted in vivo to an active NSAID analgesic. Specifically, the prodrug is converted by liver enzymes to a sulfide which is excreted in the bile and then reabsorbed from the intestine. This helps to maintain constant blood levels with reduced gastrointestinal side effects.. sulindac : A monocarboxylic acid that is 1-benzylidene-1H-indene which is substituted at positions 2, 3, and 5 by methyl, carboxymethyl, and fluorine respectively, and in which the phenyl group of the benzylidene moiety is substituted at the para position by a methylsulfinyl group. It is a prodrug for the corresponding sulfide, a non-steroidal anti-inflammatory drug, used particularly in the treatment of acute and chronic inflammatory conditions.		6.4133monocarboxylic acid;
organofluorine compound;
sulfoxide		analgesic;
antineoplastic agent;
antipyretic;
apoptosis inducer;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
prodrug;
tocolytic agent
xl147
[no description available]		9.4511aromatic amine;
benzothiadiazole;
quinoxaline derivative;
sulfonamide		antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
thioguanine anhydrous
Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.. tioguanine : A 2-aminopurine that is the 6-thiono derivative of 2-amino-1,9-dihydro-6H-purine. Incorporates into DNA and inhibits synthesis. Used in the treatment of leukaemia.		7.58942-aminopurinesanticoronaviral agent;
antimetabolite;
antineoplastic agent
thiourea
Thiourea: A photographic fixative used also in the manufacture of resins. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance may reasonably be anticipated to be a carcinogen (Merck Index, 9th ed). Many of its derivatives are ANTITHYROID AGENTS and/or FREE RADICAL SCAVENGERS.. thiourea : The simplest member of the thiourea class, consisting of urea with the oxygen atom substituted by sulfur.		2.7430one-carbon compound;
thioureas;
ureas		antioxidant;
chromophore
D-fructopyranose
[no description available]		3.3711cyclic hemiketal;
D-fructose;
fructopyranose		sweetening agent
digoxin
Digoxin: A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666). digoxin : A cardenolide glycoside that is digitoxin beta-hydroxylated at C-12. A cardiac glycoside extracted from the foxglove plant, Digitalis lanata, it is used to control ventricular rate in atrial fibrillation and in the management of congestive heart failure with atrial fibrillation, but the margin between toxic and therapeutic doses is small.		7.3110cardenolide glycoside;
steroid saponin		anti-arrhythmia drug;
cardiotonic drug;
EC 3.6.3.9 (Na(+)/K(+)-transporting ATPase) inhibitor;
epitope
tamoxifen
[no description available]		13.324821stilbenoid;
tertiary amino compound		angiogenesis inhibitor;
antineoplastic agent;
bone density conservation agent;
EC 1.2.3.1 (aldehyde oxidase) inhibitor;
EC 2.7.11.13 (protein kinase C) inhibitor;
estrogen antagonist;
estrogen receptor antagonist;
estrogen receptor modulator
nadp
[no description available]		2.4110
ranitidine
Ranitidine: A non-imidazole blocker of those histamine receptors that mediate gastric secretion (H2 receptors). It is used to treat gastrointestinal ulcers.. ranitidine : A member of the class of furans used to treat peptic ulcer disease (PUD) and gastroesophageal reflux disease.		4.131C-nitro compound;
furans;
organic sulfide;
tertiary amino compound		anti-ulcer drug;
drug allergen;
environmental contaminant;
H2-receptor antagonist;
xenobiotic
u 0126
U 0126: protein kinase kinase inhibitor; structure in first source		2.0810aryl sulfide;
dinitrile;
enamine;
substituted aniline		antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
osteogenesis regulator;
vasoconstrictor agent
lithium
Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight [6.938; 6.997]. Salts of lithium are used in treating BIPOLAR DISORDER.		7.0510alkali metal atom
cobaltous chloride
cobaltous chloride: RN given refers to unlabeled cpd; RN in Chemline for cobalt trichloride: 10241-04-0; RN for 60-labeled cpd: 14543-09-0; RN for 57-labeled cpd: 164113-89-1; RN for 58-labeled cpd: 29377-09-1; structure. cobalt dichloride : A cobalt salt in which the cobalt metal is in the +2 oxidation state and the counter-anion is chloride. It is used as an indicator for water in desiccants.		2.1710cobalt salt;
inorganic chloride		allergen;
calcium channel blocker;
sensitiser;
two-colour indicator
nitrogen dioxide
Nitrogen Dioxide: Nitrogen oxide (NO2). A highly poisonous gas. Exposure produces inflammation of lungs that may only cause slight pain or pass unnoticed, but resulting edema several days later may cause death. (From Merck, 11th ed) It is a major atmospheric pollutant that is able to absorb UV light that does not reach the earth's surface.		4.6111nitrogen oxide
amrubicin
amrubicin: structure in first source; a 9-amino-anthracycline antibiotic. amrubicin : A synthetic anthracycline antibiotic with molecular formula C25H25NO9. A specific inhibitor of topoisomerase II, it is used (particularly as the hydrochloride salt) in the treatment of cancer, especially lung cancer, where it is a prodrug for the active metabolite, ambrucinol.		10.132311anthracycline antibiotic;
methyl ketone;
primary amino compound;
quinone;
tetracenes		antineoplastic agent;
prodrug;
topoisomerase II inhibitor
ethylenediamine platinum(ii) malonate
[no description available]		2.8840
didimethylsulfoxide dichloroplatinum(ii)
[no description available]		5.8571
e 7010
E 7010: inhibits tubulin polymerization; structure given in first source		4.3711sulfonamide
dasatinib
N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1,3-thiazole-5-carboxamide: a dasatinib prodrug; structure in first source. dasatinib (anhydrous) : An aminopyrimidine that is 2-methylpyrimidine which is substituted at position 4 by the primary amino group of 2-amino-1,3-thiazole-5-carboxylic acid and at position 6 by a 4-(2-hydroxyethyl)piperazin-1-yl group, and in which the carboxylic acid group has been formally condensed with 2-chloro-6-methylaniline to afford the corresponding amide. A multi-targeted kinase inhibitor, it is used, particularly as the monohydrate, for the treatment of chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia. Note that the name 'dasatinib' is used to refer to the monohydrate (USAN) as well as to anhydrous dasatinib (INN).		6.41721,3-thiazoles;
aminopyrimidine;
monocarboxylic acid amide;
N-(2-hydroxyethyl)piperazine;
N-arylpiperazine;
organochlorine compound;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antineoplastic agent;
tyrosine kinase inhibitor
oxalylglycine
oxalylglycine: structure given in first source. N-oxalylglycine : An amino dicarboxylic acid that is iminodiacetic acid with an oxo substituent. It is used as an inhibitor of alpha-ketoglutarate dependent (EC 1.14.11.*) enzymes.		2.0510amino dicarboxylic acid;
N-acylglycine		EC 1.14.11.* (oxidoreductase acting on paired donors, 2-oxoglutarate as one donor, incorporating 1 atom each of oxygen into both donors) inhibitor
zd 6474
CH 331: structure in first source		7.1675aromatic ether;
organobromine compound;
organofluorine compound;
piperidines;
quinazolines;
secondary amine		antineoplastic agent;
tyrosine kinase inhibitor
calixarenes
Calixarenes: Phenolic metacyclophanes derived from condensation of PHENOLS and ALDEHYDES. The name derives from the vase-like molecular structures. A bracketed [n] indicates the number of aromatic rings.. calixarenes : Originally macrocyclic compounds capable of assuming a basket (or "calix") shaped conformation. They are formed from p-hydrocarbyl phenols and formaldehyde. The term now applies to a variety of derivatives by substitution of the hydrocarbon cyclo{oligo[(1,3-phenylene)methylene]}.. calixarene : A macrocycle composed of 1,3-phenylene groups linked by methylene groups. The number of 1,3-phenylene units in the macrocycle is denoted by the "n" in calix[n]arene name.		2.1110
salinomycin
salinomycin: from Streptomyces albus; RN given refers to parent cpd; structure		2.2110polyketide;
spiroketal		animal growth promotant;
potassium ionophore
ovalbumin
Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.		3.3220
dimethyldithiocarbamate
Dimethyldithiocarbamate: A chemical that acts as a dopamine beta-hydroxylase inhibitor. Its salts are agricultural fungicides. It is inferior to diethyldithiocarbamate as a chelating agent.. dimethyldithiocarbamate : A member of the class of dithiocarbamate anions resulting from the removal of the proton from the dithiocarbamic acid moiety of dimethyldithiocarbamic acid. The major species at pH 7.3.		2.0210dithiocarbamate anions
alpha-chymotrypsin
Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.		3.3711
naphthoquinones
Naphthoquinones: Naphthalene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.		5.6961
osteoprotegerin
Osteoprotegerin: A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.		2.0210long-chain fatty acid
rhodamine 123
Rhodamine 123: A fluorescent probe with low toxicity which is a potent substrate for ATP BINDING CASSETTE TRANSPORTER, SUBFAMILY B, MEMBER 1 and the bacterial multidrug efflux transporter. It is used to assess mitochondrial bioenergetics in living cells and to measure the efflux activity of ATP BINDING CASSETTE TRANSPORTER, SUBFAMILY B, MEMBER 1 in both normal and malignant cells. (Leukemia 1997;11(7):1124-30). rhodamine 123(1+) : A cationic fluorescent dye derived from 9-phenylxanthene.		2.730organic cation;
xanthene dye		fluorochrome
tetrathiomolybdate
tetrathiomolybdate: RN given refers to (MoS4)-2; chelates copper; inhibits CopB copper ATPase and cytokine proteins important for angiogenesis; structure		2.0510
sphingosine
sphing-4-enine : A sphingenine in which the C=C double bond is located at the 4-position.. sphingenine : A 2-aminooctadecene-1,3-diol having (2S,3R)-configuration.. sphingoid : Sphinganine, its homologs and stereoisomers, and the hydroxy and unsaturated derivatives of these compounds.. 2-aminooctadec-4-ene-1,3-diol : A 2-aminooctadecene-1,3-diol having its double bond at position 4.		2.4620sphing-4-eninehuman metabolite;
mouse metabolite
quercetin
[no description available]		2.99407-hydroxyflavonol;
pentahydroxyflavone		antibacterial agent;
antineoplastic agent;
antioxidant;
Aurora kinase inhibitor;
chelator;
EC 1.10.99.2 [ribosyldihydronicotinamide dehydrogenase (quinone)] inhibitor;
geroprotector;
phytoestrogen;
plant metabolite;
protein kinase inhibitor;
radical scavenger
bilirubin
[no description available]		2.4420biladienes;
dicarboxylic acid		antioxidant;
human metabolite;
mouse metabolite
dinoprostone
prostaglandin E2 : Prostaglandin F2alpha in which the hydroxy group at position 9 has been oxidised to the corresponding ketone. Prostaglandin E2 is the most common and most biologically potent of mammalian prostaglandins.		4.8221prostaglandins Ehuman metabolite;
mouse metabolite;
oxytocic
arachidonyltrifluoromethane
arachidonyltrifluoromethane: structure given in first source; inhibits 85-kDa phospholipase A2. AACOCF3 : A fatty acid derivative that is arachidonic acid in which the OH part of the carboxy group has been replaced by a trifluoromethyl group		2.5220fatty acid derivative;
ketone;
olefinic compound;
organofluorine compound		EC 3.1.1.4 (phospholipase A2) inhibitor
luteolin
[no description available]		2.6103'-hydroxyflavonoid;
tetrahydroxyflavone		angiogenesis inhibitor;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
c-Jun N-terminal kinase inhibitor;
EC 2.3.1.85 (fatty acid synthase) inhibitor;
immunomodulator;
nephroprotective agent;
plant metabolite;
radical scavenger;
vascular endothelial growth factor receptor antagonist
calcitriol
dihydroxy-vitamin D3: as a major in vitro metabolite of 1alpha,25-dihydroxyvitamin D3, produced in primary cultures of neonatal human keratinocytes		10.3472D3 vitamins;
hydroxycalciol;
triol		antineoplastic agent;
antipsoriatic;
bone density conservation agent;
calcium channel agonist;
calcium channel modulator;
hormone;
human metabolite;
immunomodulator;
metabolite;
mouse metabolite;
nutraceutical
vitamin k semiquinone radical
vitamin K semiquinone radical: found in active preparations of vitamin K-dependent carboxylase. vitamin K : Any member of a group of fat-soluble 2-methyl-1,4-napthoquinones that exhibit biological activity against vitamin K deficiency. Vitamin K is required for the synthesis of prothrombin and certain other blood coagulation factors.		1.9910
alprostadil
[no description available]		4.3422prostaglandins Eanticoagulant;
human metabolite;
platelet aggregation inhibitor;
vasodilator agent
cholecalciferol
Cholecalciferol: Derivative of 7-dehydroxycholesterol formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. It differs from ERGOCALCIFEROL in having a single bond between C22 and C23 and lacking a methyl group at C24.. calciol : A hydroxy seco-steroid that is (5Z,7E)-9,10-secocholesta-5,7,10(19)-triene in which the pro-S hydrogen at position 3 has been replaced by a hydroxy group. It is the inactive form of vitamin D3, being hydroxylated in the liver to calcidiol (25-hydroxyvitamin D3), which is then further hydroxylated in the kidney to give calcitriol (1,25-dihydroxyvitamin D3), the active hormone.		5.2231D3 vitamins;
hydroxy seco-steroid;
seco-cholestane;
secondary alcohol;
steroid hormone		geroprotector;
human metabolite
rutin
Hydroxyethylrutoside: Monohydroxyethyl derivative of rutin. Peripheral circulation stimulant used in treatment of venous disorders.		3.3811disaccharide derivative;
quercetin O-glucoside;
rutinoside;
tetrahydroxyflavone		antioxidant;
metabolite
harmine
Harmine: Alkaloid isolated from seeds of PEGANUM HARMALA; ZYGOPHYLLACEAE. It is identical to banisterine, or telepathine, from Banisteria caapi and is one of the active ingredients of hallucinogenic drinks made in the western Amazon region from related plants. It has no therapeutic use, but (as banisterine) was hailed as a cure for postencephalitic PARKINSON DISEASE in the 1920's.. harmine : A harmala alkaloid in which the harman skeleton is methoxy-substituted at C-7.		2.1510harmala alkaloidanti-HIV agent;
EC 1.4.3.4 (monoamine oxidase) inhibitor;
metabolite
genistein
[no description available]		2.42207-hydroxyisoflavonesantineoplastic agent;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
geroprotector;
human urinary metabolite;
phytoestrogen;
plant metabolite;
tyrosine kinase inhibitor
amphotericin b
Amphotericin B: Macrolide antifungal antibiotic produced by Streptomyces nodosus obtained from soil of the Orinoco river region of Venezuela.. amphotericin B : A macrolide antibiotic used to treat potentially life-threatening fungal infections.		4.5980antibiotic antifungal drug;
macrolide antibiotic;
polyene antibiotic		antiamoebic agent;
antiprotozoal drug;
bacterial metabolite
humulene
humulene: structure given in first source. (1E,4E,8E)-alpha-humulene : The (1E,4E,8E)-isomer of alpha-humulene.		2.0110alpha-humulene
amentoflavone
[no description available]		2.6620biflavonoid;
hydroxyflavone;
ring assembly		angiogenesis inhibitor;
antiviral agent;
cathepsin B inhibitor;
P450 inhibitor;
plant metabolite
baicalein
[no description available]		4.6111trihydroxyflavoneangiogenesis inhibitor;
anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
antifungal agent;
antineoplastic agent;
antioxidant;
apoptosis inducer;
EC 1.13.11.31 (arachidonate 12-lipoxygenase) inhibitor;
EC 1.13.11.33 (arachidonate 15-lipoxygenase) inhibitor;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
EC 4.1.1.17 (ornithine decarboxylase) inhibitor;
ferroptosis inhibitor;
geroprotector;
hormone antagonist;
plant metabolite;
prostaglandin antagonist;
radical scavenger
chrysin
chrysin : A dihydroxyflavone in which the two hydroxy groups are located at positions 5 and 7.		7.41107-hydroxyflavonol;
dihydroxyflavone		anti-inflammatory agent;
antineoplastic agent;
antioxidant;
EC 2.7.11.18 (myosin-light-chain kinase) inhibitor;
hepatoprotective agent;
plant metabolite
3-methylquercetin
isorhamnetin : A monomethoxyflavone that is quercetin in which the hydroxy group at position 3' is replaced by a methoxy group.		2.11107-hydroxyflavonol;
monomethoxyflavone;
tetrahydroxyflavone		anticoagulant;
EC 1.14.18.1 (tyrosinase) inhibitor;
metabolite
myricetin
[no description available]		2.41107-hydroxyflavonol;
hexahydroxyflavone		antineoplastic agent;
antioxidant;
cyclooxygenase 1 inhibitor;
food component;
geroprotector;
hypoglycemic agent;
plant metabolite
daidzein
[no description available]		2.03107-hydroxyisoflavonesantineoplastic agent;
EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor;
EC 3.2.1.20 (alpha-glucosidase) inhibitor;
phytoestrogen;
plant metabolite
maytansine
Maytansine: An ansa macrolide isolated from the MAYTENUS genus of East African shrubs.. maytansine : An organic heterotetracyclic compound and 19-membered macrocyclic lactam antibiotic originally isolated from the Ethiopian shrub Maytenus serrata but also found in other Maytenus species. It exhibits cytotoxicity against many tumour cell lines.		8.3373alpha-amino acid ester;
carbamate ester;
epoxide;
maytansinoid;
organic heterotetracyclic compound;
organochlorine compound		antimicrobial agent;
antimitotic;
antineoplastic agent;
plant metabolite;
tubulin modulator
sdz psc 833
valspodar: nonimmunosuppressive cyclosporin analog which is a potent multidrug resistance modifier; 7-10 fold more potent than cyclosporin A; a potent P glycoprotein inhibitor; MW 1215		4.3722homodetic cyclic peptide
n,n-dimethylsphingenine
N,N-dimethylsphingosine: a sphingosine kinase inhibitor. N,N-dimethylsphingosine : A sphingoid that is sphingosine in which the two amino hydrogens are replaced by methyl groups.		2.0210aminodiol;
sphingoid;
tertiary amino compound		EC 2.7.1.91 (sphingosine kinase) inhibitor;
metabolite
isotretinoin
Isotretinoin: A topical dermatologic agent that is used in the treatment of ACNE VULGARIS and several other skin diseases. The drug has teratogenic and other adverse effects.. isotretinoin : A retinoic acid that is all-trans-retinoic acid in which the double bond which is alpha,beta- to the carboxy group is isomerised to Z configuration. A synthetic retinoid, it is used for the treatment of severe cases of acne and other skin diseases.		14.38114retinoic acidantineoplastic agent;
keratolytic drug;
teratogenic agent
misoprostol
Misoprostol: A synthetic analog of natural prostaglandin E1. It produces a dose-related inhibition of gastric acid and pepsin secretion, and enhances mucosal resistance to injury. It is an effective anti-ulcer agent and also has oxytocic properties.. misoprostol : A diastereoisomeric mixture composed of approximately equal amounts of a double racemate of four of the sixteen possible diastereoisomers of methyl (13E)-11,16-dihydroxy-16-methyl-9-oxoprost-13-en-1-oate that is racemic prostaglandin E1 which is lacking the hydroxy group at position 15, but which has an additional hydroxy group at position 16. It is a synthetic prostaglandin E1 analogue, used in the treatment of gastric and duodenal ulcers. A weak abortifacient, it is also used for cervical ripening prior to surgical termination of pregnancy. The (11R,16S)-diastereoisomer is the pharmacologically active form.		3.3711
pitavastatin
pitavastatin : A dihydroxy monocarboxylic acid that is (6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]hept-6-enoic acid in which the two hydroxy groups are located at positions 3 and 5 (the 3R,5S-stereoisomer). Used as its calcium salt for treatment of hypercholesterolemia (elevated levels of cholesterol in the blood) on patients unable to sufficiently lower their cholesterol levels by diet and exercise.		7.4110cyclopropanes;
dihydroxy monocarboxylic acid;
monofluorobenzenes;
quinolines;
statin (synthetic)		antioxidant
4-hydroxy-2-nonenal
4-hydroxy-2-nonenal: cytotoxic product from peroxidation of liver microsomal lipids; RN given refers to cpd without isomeric designation. 4-hydroxynon-2-enal : An enal consisting of non-2-ene having an oxo group at the 1-position and a hydroxy group at the 4-position.. 4-hydroxynonenal : A monounsaturated fatty aldehyde that is nonanal that has undergone dehydrogenation to introduce a double bond at any position in the aliphatic chain and in which a hydrogen at position 4 has been replaced by a hydroxy group.		2.13104-hydroxynon-2-enal;
4-hydroxynonenal
menaquinone 6
menaquinone 6: RN given refers to (all-E)-isomer		4.6111
sphingosine 1-phosphate
sphingosine 1-phosphate: RN given refers to (R-(R*,S*-(E)))-isomer; RN for cpd without isomeric designation not available 8/89. sphingosine 1-phosphate : A phosphosphingolipid that consists of sphingosine having a phospho group attached at position 1		2.1110sphingoid 1-phosphatemouse metabolite;
signalling molecule;
sphingosine-1-phosphate receptor agonist;
T-cell proliferation inhibitor;
vasodilator agent
mitolactol
Mitolactol: Alkylating antineoplastic toxic to bone marrow; used in breast cancer, also in combination with other drugs.		1.9710alcohol;
organobromine compound
phenylephrine hydrochloride
Nose: A part of the upper respiratory tract. It contains the organ of SMELL. The term includes the external nose, the nasal cavity, and the PARANASAL SINUSES.. phenylephrine hydrochloride : A hydrochloride that is the monohydrochloride salt of phenylephrine.		2.6320hydrochloride
rutin sulfate
rutin sulfate: RN refers to Na salt		3.3811
granisetron
Granisetron: A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic for cancer chemotherapy patients.. granisetron : A monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 1-methyl-1H-indazole-3-carboxylic acid with the primary amino group of (3-endo)-9-methyl-9-azabicyclo[3.3.1]nonan-3-amine. A selective 5-HT3 receptor antagonist, it is used (generally as the monohydrochloride salt) to manage nausea and vomiting caused by cancer chemotherapy and radiotherapy, and to prevent and treat postoperative nausea and vomiting.		10.762320aromatic amide;
indazoles
levetiracetam
Levetiracetam: A pyrrolidinone and acetamide derivative that is used primarily for the treatment of SEIZURES and some movement disorders, and as a nootropic agent.. levetiracetam : A pyrrolidinone and carboxamide that is N-methylpyrrolidin-2-one in which one of the methyl hydrogens is replaced by an aminocarbonyl group, while another is replaced by an ethyl group (the S enantiomer). An anticonvulsant, it is used for the treatment of epilepsy in both human and veterinary medicine.		2.2510pyrrolidin-2-onesanticonvulsant;
environmental contaminant;
xenobiotic
sirolimus
Sirolimus: A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.. sirolimus : A macrolide lactam isolated from Streptomyces hygroscopicus consisting of a 29-membered ring containing 4 trans double bonds, three of which are conjugated. It is an antibiotic, immunosupressive and antineoplastic agent.		12.923013antibiotic antifungal drug;
cyclic acetal;
cyclic ketone;
ether;
macrolide lactam;
organic heterotricyclic compound;
secondary alcohol		antibacterial drug;
anticoronaviral agent;
antineoplastic agent;
bacterial metabolite;
geroprotector;
immunosuppressive agent;
mTOR inhibitor
topiramate
Topiramate: A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of EPILEPSY and MIGRAINE DISORDERS, and may also promote weight loss.. topiramate : A hexose derivative that is 2,3:4,5-di-O-isopropylidene-beta-D-fructopyranose in which the hydroxy group has been converted to the corresponding sulfamate ester. It blocks voltage-dependent sodium channels and is used as an antiepileptic and for the prevention of migraine.		3.3711cyclic ketal;
ketohexose derivative;
sulfamate ester		anticonvulsant;
sodium channel blocker
gamma-cyclodextrin
gamma-cyclodextrin : A cycloamylose composed of eight alpha-(1->4) linked D-glucopyranose units.		2.4320cyclodextrin
menaquinone 7
menaquinone-7 : A menaquinone whose side-chain contains seven isoprene units in an all-trans-configutation.		4.6111menaquinonebone density conservation agent;
cofactor;
Escherichia coli metabolite;
human blood serum metabolite;
Mycoplasma genitalium metabolite
alvocidib
alvocidib: structure given in first source. alvocidib : A synthetic dihydroxyflavone that is 5,7-dihydroxyflavone which is substituted by a 3-hydroxy-1-methylpiperidin-4-yl group at position 8 and by a chlorine at the 2' position (the (-)-3S,4R stereoisomer). A cyclin-dependent kinase 9 (CDK9) inhibitor, it has been studied for the treatment of acute myeloid leukaemia, arthritis and atherosclerotic plaque formation.		10.6163dihydroxyflavone;
hydroxypiperidine;
monochlorobenzenes;
tertiary amino compound		antineoplastic agent;
antirheumatic drug;
apoptosis inducer;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
fenretinide
Fenretinide: A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.. 4-hydroxyphenyl retinamide : A retinoid obtained by formal condensation of the carboxy group of all-trans retinoic acid and the anilino group of 4-hydroxyaniline. Synthetic retinoid agonist. Antiproliferative, antioxidant and anticancer agent with a long half-life in vivo. Apoptotic effects appear to be mediated by a mechanism distinct from that of 'classical' retinoids.		210monocarboxylic acid amide;
retinoid		antineoplastic agent;
antioxidant
morphine
Meconium: The thick green-to-black mucilaginous material found in the intestines of a full-term fetus. It consists of secretions of the INTESTINAL GLANDS; BILE PIGMENTS; FATTY ACIDS; AMNIOTIC FLUID; and intrauterine debris. It constitutes the first stools passed by a newborn.		2.7130morphinane alkaloid;
organic heteropentacyclic compound;
tertiary amino compound		anaesthetic;
drug allergen;
environmental contaminant;
geroprotector;
mu-opioid receptor agonist;
opioid analgesic;
plant metabolite;
vasodilator agent;
xenobiotic
deamino arginine vasopressin
Deamino Arginine Vasopressin: A synthetic analog of the pituitary hormone, ARGININE VASOPRESSIN. Its action is mediated by the VASOPRESSIN receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating FACTOR VIII and VON WILLEBRAND FACTOR.		2.7130heterodetic cyclic peptidediagnostic agent;
renal agent;
vasopressin receptor agonist
dexmedetomidine
[no description available]		2.0710medetomidinealpha-adrenergic agonist;
analgesic;
non-narcotic analgesic;
sedative
andrographolide
[no description available]		7.2110carbobicyclic compound;
gamma-lactone;
labdane diterpenoid;
primary alcohol;
secondary alcohol		anti-HIV agent;
anti-inflammatory drug;
antineoplastic agent;
metabolite
casein kinase ii
Casein Kinase II: A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.		2.4520
orantinib
orantinib: an antiangiogenic agent. orantinib : An oxindole that is 3-methyleneoxindole in which one of the hydrogens of the methylene group is substituted by a 2-(2-carboxyethyl)-3,5-dimethylpyrrol-3-yl group. It is an ATP-competitive inhibitor of the tyrosine kinase activity of fibroblast growth factor receptor 1.		3.4611
su 11248
[no description available]		8.9398monocarboxylic acid amide;
pyrroles		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
immunomodulator;
neuroprotective agent;
vascular endothelial growth factor receptor antagonist
palbociclib
[no description available]		9.8421aminopyridine;
aromatic ketone;
cyclopentanes;
piperidines;
pyridopyrimidine;
secondary amino compound;
tertiary amino compound		antineoplastic agent;
EC 2.7.11.22 (cyclin-dependent kinase) inhibitor
mitoguazone
Mitoguazone: Antineoplastic agent effective against myelogenous leukemia in experimental animals. Also acts as an inhibitor of animal S-adenosylmethionine decarboxylase.. mitoguazone : A hydrazone obtained by formal condensation of the two carbonyl groups of methylglyoxal with the primary amino groups of two molecules of aminoguanidine.		2.3720guanidines;
hydrazone		antineoplastic agent;
apoptosis inducer;
EC 4.1.1.50 (adenosylmethionine decarboxylase) inhibitor
fosbretabulin
fosbretabulin: a microtubule destabilizing agent isolated from Combretum caffrum; structure in first source		7.2464
lead
Lead: A soft, grayish metal with poisonous salts; atomic number 82, atomic weight 207.2, symbol Pb.		4.6111carbon group element atom;
elemental lead;
metal atom		neurotoxin
8-oxo-7,8-dihydrodeoxyguanine
8-oxo-7,8-dihydrodeoxyguanine: structure given in first source		3.4411
arsenic
Arsenic: A shiny gray element with atomic symbol As, atomic number 33, and atomic weight 75. It occurs throughout the universe, mostly in the form of metallic arsenides. Most forms are toxic. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), arsenic and certain arsenic compounds have been listed as known carcinogens. (From Merck Index, 11th ed)		5.2431metalloid atom;
pnictogen		micronutrient
naltrexone
Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of NALOXONE. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence.. naltrexone : An organic heteropentacyclic compound that is naloxone substituted in which the allyl group attached to the nitrogen is replaced by a cyclopropylmethyl group. A mu-opioid receptor antagonist, it is used to treat alcohol dependence.		7.1710cyclopropanes;
morphinane-like compound;
organic heteropentacyclic compound		antidote to opioid poisoning;
central nervous system depressant;
environmental contaminant;
mu-opioid receptor antagonist;
xenobiotic
gallium
Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72.. gallium atom : A metallic element predicted as eka-aluminium by Mendeleev in 1870 and discovered by Paul-Emile Lecoq de Boisbaudran in 1875. Named in honour of France (Latin Gallia) and perhaps also from the Latin gallus cock, a translation of Lecoq.		4.2930boron group element atom
elsamicin a
elsamicin A: from actinomycete strain J907-21; structure given in first source		3.3811
batimastat
batimastat: structure given in first source; a synthetic matrix metalloproteinase inhibitor. batimastat : A secondary carboxamide resulting from the formal condensation of the carboxy group of (2S,3R)-5-methyl-3-{[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl}-2-[(thiophen-2-ylsulfanyl)methyl]hexanoic acid with the amino group of hydroxylamine. It a broad-spectrum matrix metalloprotease inhibitor.		1.9910hydroxamic acid;
L-phenylalanine derivative;
organic sulfide;
secondary carboxamide;
thiophenes;
triamide		angiogenesis inhibitor;
antineoplastic agent;
matrix metalloproteinase inhibitor
sulfur
Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight [32.059; 32.076]. It is found in the amino acids cysteine and methionine.		2.3920chalcogen;
nonmetal atom		macronutrient
enalapril
Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat HYPERTENSION and HEART FAILURE.. enalapril : A dicarboxylic acid monoester that is ethyl 4-phenylbutanoate in which a hydrogen alpha to the carboxy group is substituted by the amino group of L-alanyl-L-proline (S-configuration).		2.0410dicarboxylic acid monoester;
dipeptide		antihypertensive agent;
EC 3.4.15.1 (peptidyl-dipeptidase A) inhibitor;
geroprotector;
prodrug
fumarates
Fumarates: Compounds based on fumaric acid.. fumarate(2-) : A C4-dicarboxylate that is the E-isomer of but-2-enedioate(2-)		2.4110butenedioate;
C4-dicarboxylate		human metabolite;
metabolite;
Saccharomyces cerevisiae metabolite
cysteine
Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.. L-cysteinium : The L-enantiomer of cysteinium.. cysteine : A sulfur-containing amino acid that is propanoic acid with an amino group at position 2 and a sulfanyl group at position 3.		9.8371cysteiniumfundamental metabolite
phosphorus
Phosphorus: A non-metal element that has the atomic symbol P, atomic number 15, and atomic weight 31. It is an essential element that takes part in a broad variety of biochemical reactions.		4.6111monoatomic phosphorus;
nonmetal atom;
pnictogen		macronutrient
heroin
Heroin: A narcotic analgesic that may be habit-forming. It is a controlled substance (opium derivative) listed in the U.S. Code of Federal Regulations, Title 21 Parts 329.1, 1308.11 (1987). Sale is forbidden in the United States by Federal statute. (Merck Index, 11th ed). heroin : A morphinane alkaloid that is morphine bearing two acetyl substituents on the O-3 and O-6 positions. As with other opioids, heroin is used as both an analgesic and a recreational drug. Frequent and regular administration is associated with tolerance and physical dependence, which may develop into addiction. Its use includes treatment for acute pain, such as in severe physical trauma, myocardial infarction, post-surgical pain, and chronic pain, including end-stage cancer and other terminal illnesses.		1.9710morphinane alkaloidmu-opioid receptor agonist;
opioid analgesic;
prodrug
sulindac sulfone
sulindac sulfone: inhibits K-ras-dependent cyclooxygenase-2; sulfated analog of indomethacin;; CP248 is an antineoplastic agent that fosters microtubule depolymerization; structure in first source. sulindac sulfone : A sulfone metabolite of sulindac that inhibits cell growth by inducing apoptosis independently of cyclooxygenase inhibition. It inhibits the development and induces regression of premalignant adenomatous polyps. Lipoxygenase and Cox-2 inhibitor.		6.4133monocarboxylic acid;
organofluorine compound;
sulfone		apoptosis inducer;
cyclooxygenase 2 inhibitor;
EC 1.13.11.34 (arachidonate 5-lipoxygenase) inhibitor
cefepime
Cefepime: A fourth-generation cephalosporin antibacterial agent that is used in the treatment of infections, including those of the abdomen, urinary tract, respiratory tract, and skin. It is effective against PSEUDOMONAS AERUGINOSA and may also be used in the empiric treatment of FEBRILE NEUTROPENIA.. cefepime : A cephalosporin bearing (1-methylpyrrolidinium-1-yl)methyl and (2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido groups at positions 3 and 7, respectively, of the cephem skeleton.		2.6120cephalosporin;
oxime O-ether		antibacterial drug
strontium radioisotopes
Strontium Radioisotopes: Unstable isotopes of strontium that decay or disintegrate spontaneously emitting radiation. Sr 80-83, 85, and 89-95 are radioactive strontium isotopes.		3.3711
aliskiren
aliskiren: orally active nonpeptidic renin inhibitor. aliskiren : A monomethoxybenzene compound having a 3-methoxypropoxy group at the 2-position and a multi-substituted branched alkyl substituent at the 4-position.		2.4110monocarboxylic acid amide;
monomethoxybenzene		antihypertensive agent
isocoumarin nm-3
isocoumarin NM-3: a synthetic derivative of cytogenin; structure in first source		2.4320
vx680
[no description available]		2.0710N-arylpiperazine
salubrinal
salubrinal: prevents dephosphorylation of eIF2alpha; structure in first source. salubrinal : A member of the class of quinolines that is a mixed aminal resulting from the formal condensation oftrichloroacetaldehyde with the amide nitrogen of trans-cinnamamide and the primary amino group of 1-quinolin-8-ylthiourea. It is a selective inhibitor of cellular complexes that dephosphorylate eukaryotic translation initiation factor 2 subunit alpha (eIF2alpha).		2.0810aminal;
organochlorine compound;
quinolines;
secondary carboxamide;
thioureas
cefotaxime
Cefotaxime: Semisynthetic broad-spectrum cephalosporin.. cefotaxime : A cephalosporin compound having acetoxymethyl and [2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino side groups.		1.97101,3-thiazoles;
cephalosporin;
oxime O-ether		antibacterial drug;
drug allergen
4,4'-diisothiocyanostilbene-2,2'-disulfonic acid
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid: An inhibitor of anion conductance including band 3-mediated anion transport.		2.4620
selenium
Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.97. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of GLUTATHIONE PEROXIDASE.		5.732chalcogen;
nonmetal atom		micronutrient
oxalates
Oxalates: Derivatives of OXALIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that are derived from the ethanedioic acid structure.		3.8530
palonosetron
Palonosetron: Isoquinoline and quinuclidine derivative that acts as a 5-HT3 RECEPTOR antagonist. It is used in the prevention of nausea and vomiting induced by cytotoxic chemotherapy, and for the prevention of post-operative nausea and vomiting.. palonosetron : An organic heterotricyclic compound that is an antiemetic used (as its hydrochloride salt) in combination with netupitant (under the trade name Akynzeo) to treat nausea and vomiting in patients undergoing cancer chemotherapy.		8.731810azabicycloalkane;
delta-lactam;
organic heterotricyclic compound		antiemetic;
serotonergic antagonist
(3S,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid
Fluvastatin: An indole-heptanoic acid derivative that inhibits HMG COA REDUCTASE and is used to treat HYPERCHOLESTEROLEMIA. In contrast to other statins, it does not appear to interact with other drugs that inhibit CYP3A4.. (3S,5S,6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid : A (6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid diastereoisomer in which both chiral centres have S configuration.. fluvastatin : A racemate comprising equimolar amounts of (3R,5S)- and (3S,5R)-fluvastatin. An HMG-CoA reductase inhibitor, it is used (often as the corresponding sodium salt) to reduce triglycerides and LDL-cholesterol, and increase HDL-chloesterol, in the treatment of hyperlipidaemia.		3.8521(6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3,5-dihydroxyhept-6-enoic acid
agn 191659
AGN 191659: a retinoid x receptor pan-agonist; structure in first source		2.4520
s-1,2-dichlorovinyl-n-acetylcysteine
S-1,2-dichlorovinyl-N-acetylcysteine: urinary metabolite of trichloroethylene in mice		5.6822
manumycin
manumycin: an NSAID; RN given for (1S-(1alpha,3(2E,4E,6S*),5alpha,5(1E,3E,5E),6alpha))-isomer; a farnesyl protein transferase inhibitor; from Streptomyces parvulus; MF C31-H38-N2-O7; structure given in first source. manumycin A : A polyketide with formula C31H38N2O7 initially isolated from Streptomyces parvulus as a result of a random screening program for farnesyl transferase (FTase) inhibitors. It is a natural product that exhibits anticancer and antibiotic properties.		2.9510enamide;
epoxide;
organic heterobicyclic compound;
polyketide;
secondary carboxamide;
tertiary alcohol		antiatherosclerotic agent;
antimicrobial agent;
antineoplastic agent;
apoptosis inducer;
bacterial metabolite;
EC 1.8.1.9 (thioredoxin reductase) inhibitor;
EC 2.5.1.58 (protein farnesyltransferase) inhibitor;
marine metabolite
krn 5500
KRN 5500: a derivative of spicamycin with a wide range of antitumor activity against human cancer cell lines; structure given in first source		210
everolimus
[no description available]		12.262210cyclic acetal;
cyclic ketone;
ether;
macrolide lactam;
primary alcohol;
secondary alcohol		anticoronaviral agent;
antineoplastic agent;
geroprotector;
immunosuppressive agent;
mTOR inhibitor
ixabepilone
[no description available]		9.59861,3-thiazoles;
beta-hydroxy ketone;
epoxide;
lactam;
macrocycle		antineoplastic agent;
microtubule-destabilising agent
ganglioside, gd2
[no description available]		2.0510
axitinib
[no description available]		7.644aryl sulfide;
benzamides;
indazoles;
pyridines		antineoplastic agent;
tyrosine kinase inhibitor;
vascular endothelial growth factor receptor antagonist
netupitant
netupitant: orally active neurokinin-1 receptor antagonist. netupitant : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoic acid with the secondary amino group of N-methyl-4-(2-methylphenyl)-6-(4-methylpiperazin-1-yl)pyridin-3-amine; an antiemetic used in combination with palonosetron hydrochloride (under the trade name Akynzeo) to treat nausea and vomiting in patients undergoing cancer chemotherapy.		9.2631aminopyridine;
monocarboxylic acid amide;
N-alkylpiperazine;
N-arylpiperazine;
organofluorine compound;
toluenes		antiemetic;
neurokinin-1 receptor antagonist
belotecan
belotecan: structure in first source		9.2231pyranoindolizinoquinoline
tanespimycin
CP 127374: analog of herbimycin A		2.74301,4-benzoquinones;
ansamycin;
carbamate ester;
organic heterobicyclic compound;
secondary amino compound		antineoplastic agent;
apoptosis inducer;
Hsp90 inhibitor
beta-escin
[no description available]		2.7620
peplomycin
Peplomycin: An antineoplastic agent derived from BLEOMYCIN.		11.18101glycopeptide
gadolinium dtpa
Gadolinium DTPA: A complex of gadolinium with a chelating agent, diethylenetriamine penta-acetic acid (DTPA see PENTETIC ACID), that is given to enhance the image in cranial and spinal MRIs. (From Martindale, The Extra Pharmacopoeia, 30th ed, p706)		4.7490gadolinium coordination entityMRI contrast agent
ergoline
Ergolines: A series of structurally-related alkaloids that contain the ergoline backbone structure.. ergoline : An indole alkaloid whose structural skeleton is found in many naturally occurring and synthetic ergolines which are known to bind to neurotransmitter receptors, such as dopamine, noradrenaline and serotonin receptors and function as unselective agonists or antagonists at these receptors.		6.9910diamine;
ergoline alkaloid;
indole alkaloid fundamental parent;
indole alkaloid;
organic heterotetracyclic compound
romurtide
romurtide: a synthetic muramyl dipeptide analog; stimulates chemotactic mobility, phagocytic activity & superoxide production by neutrophils in mice; used for the prophylaxis of leukocytopenia during radiation therapy; structure given in first source		2.3920organic molecular entity
edatrexate
edatrexate: structure given in first source		6.4663glutamic acid derivative
enloplatin
enloplatin: structure given in first source		5.7161
etoposide phosphate
[no description available]		7.5115furonaphthodioxole
perfosfamide
[no description available]		2.9140
larotaxel
larotaxel: has antineoplastic activity		8.4411
ski 2053r
SKI 2053R: structure in first source; RN given in first source		2.730
rmp 7
RMP 7: a synthetic bradykinin analog; selectively increases uptake of molecular tracers in RG2 glial tumors		10.772914
soblidotin
soblidotin: a dolastatin 10 derivative; RN refers to (2S-(1(1R*(R*),2S*),2R*(1S*,2S*)))-isomer; structure given in first source. soblidotin : A tetrapeptide derivative of dolastatin 10. It is an inhibitor of tubulin polymerization which exhibits potent antitumor activity.		4.3822tetrapeptideantineoplastic agent;
apoptosis inducer;
microtubule-destabilising agent
bay 12-9566
Bay 12-9566: an angiogenesis inhibitor with matrix metalloproteinase inhibitory activity		8.4111biphenyls;
organochlorine compound
ac 7700
AC 7700: a vascular disrupting agent; structure in first source		4.411
bms184476
[no description available]		9.9221
bms188797
[no description available]		9.3311
belinostat
[no description available]		6.6454hydroxamic acid;
olefinic compound;
sulfonamide		antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
panobinostat
Panobinostat: An indole and hydroxamic acid derivative that acts as a HISTONE DEACETYLASE inhibitor. It is used as an antineoplastic agent in combination with BORTEZOMIB and DEXAMETHASONE for the treatment of MULTIPLE MYELOMA.. panobinostat : A hydroxamic acid obtained by formal condensation of the carboxy group of (2E)-3-[4-({[2-(2-methylindol-3-yl)ethyl]amino}methyl)phenyl]prop-2-enoic acid with the amino group of hydroxylamine. A histone deacetylase inhibitor used (as its lactate salt) in combination with bortezomib and dexamethasone for the treatment of multiple myeloma.		5.6663cinnamamides;
hydroxamic acid;
methylindole;
secondary amino compound		angiogenesis modulating agent;
antineoplastic agent;
EC 3.5.1.98 (histone deacetylase) inhibitor
bromopyruvate
[no description available]		7.1102-oxo monocarboxylic acid anion
leucyl-leucine-methyl ester
leucyl-leucine-methyl ester: RN given refers to all L-isomer		1.9810peptide
staurosporine
staurosporinium : Conjugate acid of staurosporine.		9.3541ammonium ion derivative
taxane
taxane: produced by Taxomyces andreanae		14.697114diterpene;
terpenoid fundamental parent
chlorhexidine
Chlorhexidine: A disinfectant and topical anti-infective agent used also as mouthwash to prevent oral plaque.. chlorhexidine : A bisbiguanide compound with a structure consisting of two (p-chlorophenyl)guanide units linked by a hexamethylene bridge.		1.9910biguanides;
monochlorobenzenes		antibacterial agent;
antiinfective agent
cefmenoxime
Cefmenoxime: A cephalosporin antibiotic that is administered intravenously or intramuscularly. It is active against most common gram-positive and gram-negative microorganisms, is a potent inhibitor of Enterobacteriaceae, and is highly resistant to hydrolysis by beta-lactamases. The drug has a high rate of efficacy in many types of infection and to date no severe side effects have been noted.. cefmenoxime : A third-generation cephalosporin antibiotic, bearing a 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino group at the 7beta-position and a [(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl group at the 3-position.		6.9710cephalosporinantibacterial drug
3-aminopyridine-2-carboxaldehyde thiosemicarbazone
3-aminopyridine-2-carboxaldehyde thiosemicarbazone: a neuroprotective agent; structure given in first source		2.0310
iniparib
[no description available]		11.49129carbonyl compound;
organohalogen compound
cp 547632
3-(4-bromo-2,6-difluorobenzyloxy)-5-(3-(4-pyrrolidin-1-ylbutyl)ureido)isothiazole-4-carboxylic acid amide: inhibits vascular endothelial growth factor receptor-2 tyrosine kinase; structure in first source		3.4211
plitidepsin
plitidepsin: a cyclodepsipeptide isolated from Aplidium albicans; has a pyruvoyl-proline residue instead of the lactyl-proline residue found in the linear peptide moiety of didemnin B. plitidepsin : A didemnin that is didemin B in which the hydroxy group of the 1-(2-hydroxypropanoyl)-L-prolinamide moiety has been oxidised to the corresponding ketone. It was originally isolated from the Mediterranean tunicate Aplidium albicans.		8.4511didemninanticoronaviral agent;
antineoplastic agent;
marine metabolite
lenvatinib
lenvatinib : A member of the class of quinolines that is the carboxamide of 4-{3-chloro-4-[(cyclopropylcarbamoyl)amino]phenoxy}-7-methoxyquinoline-6-carboxylic acid. A multi-kinase inhibitor and orphan drug used (as its mesylate salt) for the treatment of various types of thyroid cancer that do not respond to radioiodine.		8.563aromatic amide;
aromatic ether;
cyclopropanes;
monocarboxylic acid amide;
monochlorobenzenes;
phenylureas;
quinolines		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor;
fibroblast growth factor receptor antagonist;
orphan drug;
vascular endothelial growth factor receptor antagonist
midostaurin
midostaurin : An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine.		2.0410benzamides;
gamma-lactam;
indolocarbazole;
organic heterooctacyclic compound		antineoplastic agent;
EC 2.7.11.13 (protein kinase C) inhibitor
technetium tc 99m diphosphonate
technetium Tc 99m diphosphonate: bone seeking radiopharmaceutical whose concentration in bone depends upon regional blood flow & bone metabolism		3.3911
cabazitaxel
cabazitaxel: an antineoplastic agent; structure in first source. cabazitaxel : A tetracyclic diterpenoid that is 10-deacetylbaccatin III having O-methyl groups attached at positions 7 and 10 as well as an O-(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl group attached at position 13. Acts as a microtubule inhibitor, binds tubulin and promotes microtubule assembly and simultaneously inhibits disassembly.		4.8761tetracyclic diterpenoidantineoplastic agent;
microtubule-stabilising agent
elisidepsin
elisidepsin: antineoplastic; structure in first source. elisidepsin : A synthetic cyclodepsipeptide derived from a marine metabolite that exhibits antineoplastic properties.		8.4811cyclodepsipeptideantineoplastic agent
nu 7026
2-(morpholin-4-yl)benzo(h)chromen-4-one: a radiosensitizing agent that inhibits DNA-dependent protein kinase; structure in first source		2.110organic heterotricyclic compound;
organooxygen compound
pbox-6
PBOX-6: structure in first source		7.5220
mocetinostat
mocetinostat: undergoing phase II clinical trials for treatment of cancer. mocetinostat : A benzamide obtained by formal condensation of the carboxy group of 4-({[4-(pyridin-3-yl)pyrimidin-2-yl]amino}methyl)benzoic acid with one of the amino groups of benzene-1,2-diamine. It is an orally active and isotype-selective HDAC inhibitor which exhibits antitumour activity (IC50 = 0.15, 0.29, 1.66 and 0.59 muM for HDAC1, HDAC2, HDAC3 and HDAC11).		2.4420aminopyrimidine;
benzamides;
pyridines;
secondary amino compound;
secondary carboxamide;
substituted aniline		antineoplastic agent;
apoptosis inducer;
autophagy inducer;
cardioprotective agent;
EC 3.5.1.98 (histone deacetylase) inhibitor;
hepatotoxic agent
k201 compound
K201 compound: structure given in first source		210
lipid a
Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties.. lipid A : The glycolipid moiety of bacterial lipopolysaccharide (R can be either hydrogen or a fatty acyl group).		210dodecanoate ester;
lipid A;
tetradecanoate ester		Escherichia coli metabolite
treosulfan
treosulfan: immunosuppressant; RN given refers to (S-(R*,R*))-isomer		11.6652methanesulfonate ester
pi103
PI103: pyridofuropyrimidine antineoplastic; a potent inhibitor of class I phosphatidylinositide 3-kinases (PI3K); structure in first soruce		2.110aromatic amine;
morpholines;
organic heterotricyclic compound;
phenols;
tertiary amino compound		antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor;
mTOR inhibitor
zibotentan
ZD4054: a potent endothelin receptor A antagonist that inhibits ovarian carcinoma cell proliferation		9.3911phenylpyridine
n-((2s)-2-mercapto-1-oxo-4-(3,4,4- trimethyl-2,5-dioxo-1-imidazolidinyl)butyl)-l-leucyl-n,3- dimethyl-l-valinamide
N-((2S)-2-mercapto-1-oxo-4-(3,4,4- trimethyl-2,5-dioxo-1-imidazolidinyl)butyl)-L-leucyl-N,3- dimethyl-L-Valinamide: matrix metalloproteinase inhibitor		5.7622
motexafin gadolinium
[no description available]		2.0510
sorbitan monooleate
[no description available]		4.6111fatty acid ester
ammonium trichloro(dioxoethylene-o,o'-)tellurate
ammonium trichloro(dioxoethylene-O,O'-)tellurate: has potential therapeutic application; inhibits HIV-1 reverse transcriptase and replication		3.3711
rucaparib
AG14447: Poly(ADP-ribose) polymerase inhibitor; structure in first source		10.3441azepinoindole;
caprolactams;
organofluorine compound;
secondary amino compound		antineoplastic agent;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
cediranib
[no description available]		11.141211aromatic ether
pitolisant
pitolisant: functions as both inverse agonist and antagonist of histamine H3 receptors; structure in first source		4.6111organochlorine compound
pazopanib
pazopanib: a protein kinase inhibitor. pazopanib : A pyrimidine that is 5-(pyrimidin-2-yl}amino-2-methylbenzenesulfonamide substituted at position 4 by a (2,3-dimethylindazol-6-yl)(methyl)amino group. Used as its hydrochloride salt for treatment of kidney cancer.		9.0193aminopyrimidine;
indazoles;
sulfonamide		angiogenesis modulating agent;
antineoplastic agent;
tyrosine kinase inhibitor;
vascular endothelial growth factor receptor antagonist
sepantronium
sepantronium: a survivin suppressant with antineoplastic activity. sepantronium : An organic cation that is 1-(2-methoxyethyl)-2-methyl-1H-naphtho[2,3-d]imidazole-4,9-dione in which the nitrogen at position 3 of the napthoimidazole moiety has been alkylated by a pyrazin-2-ylmethyl group.		10.131organic cation
azd 6244
AZD 6244: a MEK inhibitor		3.5311benzimidazoles;
bromobenzenes;
hydroxamic acid ester;
monochlorobenzenes;
organofluorine compound;
secondary amino compound		anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
bibw 2992
[no description available]		9.3995aromatic ether;
enamide;
furans;
monochlorobenzenes;
organofluorine compound;
quinazolines;
secondary carboxamide;
tertiary amino compound		antineoplastic agent;
tyrosine kinase inhibitor
artenimol
artenimol: derivative of antimalarial drug artemisinin (quinghaosu)		2.0510
binimetinib
binimetinib : A member of the class of benzimidazoles that is 1-methyl-1H-benzimidazole which is substituted at positions 4, 5, and 6 by fluorine, (4-bromo-2-fluorophenyl)nitrilo, and N-(2-hydroxyethoxy)aminocarbonyl groups, respectively. It is a MEK1 and MEK2 inhibitor (IC50= 12 nM). Approved by the FDA for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation in combination with encorafenib.		11.3531benzimidazoles;
bromobenzenes;
hydroxamic acid ester;
monofluorobenzenes;
secondary amino compound		antineoplastic agent;
apoptosis inducer;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
saracatinib
[no description available]		8.4611aromatic ether;
benzodioxoles;
diether;
N-methylpiperazine;
organochlorine compound;
oxanes;
quinazolines;
secondary amino compound		anticoronaviral agent;
antineoplastic agent;
apoptosis inducer;
autophagy inducer;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor;
radiosensitizing agent
rolapitant
[no description available]		8.5111azaspiro compound;
ether;
organofluorine compound;
piperidines;
pyrrolidin-2-ones		antiemetic;
neurokinin-1 receptor antagonist
ngr peptide
[no description available]		2.0510
volasertib
BI 6727: a polo-like kinase inhibitor with broad antitumor activity; structure in first source		5.8622
vinflunine
vinflunine: inhibits tubulin assembly; structure in first source. vinflunine : An organic heteropentacyclic compound and an organic heterotetracyclic compound that is vinorelbine in which the tetrahydropyridine moiety of the heterotetracyclic part of the molecule has been redced to the corresponding piperidine, and in which the ethyl group attached to this ring has been replaced by a 1,1-difluoroethyl group.		9.37104acetate ester;
methyl ester;
organic heteropentacyclic compound;
organic heterotetracyclic compound;
semisynthetic derivative;
vinca alkaloid		antineoplastic agent
homocamptothecin
homocamptothecin: a DNA topoisomerase I antagonists, is a semisynthetic analogue of camptothecin (CPT) with a seven-membered beta-hydroxylactone resulting from the insertion of a mehthylene spacer between the alcohol moiety and the carboxyl function of the naturally occurring six-membered alpha-hydroxylactone of CPT; structure in first source		2.0210epsilon-lactone;
organic heteropentacyclic compound;
organonitrogen heterocyclic compound;
tertiary alcohol		antineoplastic agent;
EC 5.99.1.2 (DNA topoisomerase) inhibitor
ribose
ribopyranose : The pyranose form of ribose.		3.0120D-ribose;
ribopyranose
lactulose
Lactulose: A synthetic disaccharide used in the treatment of constipation and hepatic encephalopathy. It has also been used in the diagnosis of gastrointestinal disorders. (From Martindale, The Extra Pharmacopoeia, 30th ed, p887). lactulose : A synthetic galactosylfructose disaccharide used in the treatment of constipation and hepatic encephalopathy.		2.0310
abt-737
[no description available]		3.6890aromatic amine;
aryl sulfide;
biphenyls;
C-nitro compound;
monochlorobenzenes;
N-arylpiperazine;
N-sulfonylcarboxamide;
secondary amino compound;
tertiary amino compound		anti-allergic agent;
anti-inflammatory agent;
antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
mp470
[no description available]		2.2110N-arylpiperazine
zk-219477
sagopilone: has antineoplastic activity		4.3711macrolide
nystatin a1
Nystatin: Macrolide antifungal antibiotic complex produced by Streptomyces noursei, S. aureus, and other Streptomyces species. The biologically active components of the complex are nystatin A1, A2, and A3.. nystatin : A heterogeneous mixture of polyene compounds produced by cultures of Streptomyces noursei. It mainly consists of three biologically active components designated nystatin A1, nystatin A2, and nystatin A3. It is used to treat oral and dermal fungal infections.. nystatin A1 : A polyene macrolide antibiotic; part of the nystatin complex produced by several Streptomyces species. It is an antifungal antibiotic used for the treatment of topical fungal infections caused by a broad spectrum of fungal pathogens comprising yeast-like and filamentous species.		4.3422nystatins
pirarubicin
[no description available]		9.23335anthracycline
bms-690514
[no description available]		8.4711
er-086526
eribulin: a halichondrin B derivative that suppresses microtubule growth and acts as an antimitotic agent; structure in first source. eribulin : A fully synthetic macrocyclic ketone analogue of marine sponge natural products. Inhibits growth phase of microtubules via tubulin-based antimitotic mechanism, which leads to G2/M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage		6.9453cyclic ketal;
cyclic ketone;
macrocycle;
polycyclic ether;
polyether;
primary amino compound		antineoplastic agent;
microtubule-destabilising agent
verubulin
verubulin: antineoplastic; a small-molecule inhibitor of microtubule formation that is not a substrate for multidrug resistance pumps; structure in first source		8.4611
nutlin-3a
nutlin 3: an MDM2 antagonist; structure in first source		7.7730stilbenoid
abt 869
[no description available]		6.1332aromatic amine;
indazoles;
phenylureas		angiogenesis inhibitor;
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
ridaforolimus
[no description available]		9.4511macrolide lactam
carfilzomib
[no description available]		5.1842epoxide;
morpholines;
tetrapeptide		antineoplastic agent;
proteasome inhibitor
chlorophyll b
[no description available]		2.2510chlorophyllcofactor
crizotinib
Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER.. crizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)		14.321063-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amineantineoplastic agent;
biomarker;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
trametinib
[no description available]		5.4331acetamides;
aromatic amine;
cyclopropanes;
organofluorine compound;
organoiodine compound;
pyridopyrimidine;
ring assembly		anticoronaviral agent;
antineoplastic agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor;
geroprotector
losartan potassium
Erythropoietin: Glycoprotein hormone, secreted chiefly by the KIDNEY in the adult and the LIVER in the FETUS, that acts on erythroid stem cells of the BONE MARROW to stimulate proliferation and differentiation.		10.843616
calcimycin
Calcimycin: An ionophorous, polyether antibiotic from Streptomyces chartreusensis. It binds and transports CALCIUM and other divalent cations across membranes and uncouples oxidative phosphorylation while inhibiting ATPase of rat liver mitochondria. The substance is used mostly as a biochemical tool to study the role of divalent cations in various biological systems.		2.0610benzoxazole
dextrothyroxine
[no description available]		2.610
veliparib
[no description available]		14.925337benzimidazolesEC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
sepharose
agarose : A linear polysaccharide made up from alternating D-galactose and 3,6-anhydro-alpha-L-galactopyranose residues joined by alpha-(1->3)- and beta-(1->4)-linkages.		2.4920
indocyanine green
Indocyanine Green: A tricarbocyanine dye that is used diagnostically in liver function tests and to determine blood volume and cardiac output.		2.93301,1-diunsubstituted alkanesulfonate;
benzoindole;
cyanine dye
pituitrin
Pituitrin: A substance or extract from the neurohypophysis (PITUITARY GLAND, POSTERIOR).		2.4220
crinamine
crinamine: RN given for (3alpha,5alpha,11R,13beta,19alpha)-isomer; structure in first source		2.2110
tubulysin b
[no description available]		2.1710butyrate ester
demethylcantharidin
demethylcantharidin: has antineoplastic activity; structure in first source		2.7330
acid phosphatase
Acid Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2.		2.910
esorubicin
esorubicin: RN given refers to parent cpd; synthesized deriv of doxorubicin		4.8621
ifoxetine
ifoxetine: RN given is for cis isomer		2.1110
bleomycetin
bleomycetin: RN given refers to parent cpd		3.4111
tetrahydrouridine
Tetrahydrouridine: An inhibitor of nucleotide metabolism.		6.9810
cysteinyldopa
Cysteinyldopa: Found in large amounts in the plasma and urine of patients with malignant melanoma. It is therefore used in the diagnosis of melanoma and for the detection of postoperative metastases. Cysteinyldopa is believed to be formed by the rapid enzymatic hydrolysis of 5-S-glutathionedopa found in melanin-producing cells.		1.9910catecholamine;
zwitterion
nad
NAD(1-) : An anionic form of nicotinamide adenine dinucleotide arising from deprotonation of the two OH groups of the diphosphate moiety.		4.3541organophosphate oxoanioncofactor;
human metabolite;
hydrogen acceptor;
Saccharomyces cerevisiae metabolite
rrx-001
RRx-001: has antineoplastic activity; structure in first source		4.921
mdv 3100
[no description available]		2.9330(trifluoromethyl)benzenes;
benzamides;
imidazolidinone;
monofluorobenzenes;
nitrile;
thiocarbonyl compound		androgen antagonist;
antineoplastic agent
toceranib phosphate
toceranib phosphate: a tyrosine kinase inhibitor; structure in first source		5.5253
nvp-tae684
[no description available]		2.0510piperidines
cytochrome c-t
Cytochromes c: Cytochromes of the c type that are found in eukaryotic MITOCHONDRIA. They serve as redox intermediates that accept electrons from MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX III and transfer them to MITOCHONDRIAL ELECTRON TRANSPORT COMPLEX IV.		3.5580
gw 4869
GW 4869: inhibits neutral sphingomyelinase; structure in first source		2.2510
thymalfasin
Thymalfasin: A thymus hormone polypeptide found in thymosin fraction 5 (a crude thymus gland extract) but now produced by synthesis. It is used alone or with interferon as an immunomodulator for the treatment of CHRONIC HEPATITIS B and HEPATITIS C. Thymalfasin is also used for the treatment of chemotherapy-induced immunosuppression, and to enhance the efficacy of influenza and hepatitis B vaccines in immunocompromised patients.		3.411polypeptide
rpl41 protein, human
RPL41 protein, human: RefSeq NM_021104		2.3110
glucagon
Glucagon: A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal GLUCAGON-LIKE PEPTIDES. Glucagon is secreted by PANCREATIC ALPHA CELLS and plays an important role in regulation of BLOOD GLUCOSE concentration, ketone metabolism, and several other biochemical and physiological processes. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1511). glucagon : A 29-amino acid peptide hormone consisting of His, Ser, Gln, Gly, Thr, Phe, Thr, Ser, Asp, Tyr, Ser, Lys, Tyr, Leu, Asp, Ser, Arg, Arg, Ala, Gln, Asp, Phe, Val, Gln, Trp, Leu, Met, Asn and Thr residues joined in sequence.		5.0421peptide hormone
beta-endorphin
beta-Endorphin: A 31-amino acid peptide that is the C-terminal fragment of BETA-LIPOTROPIN. It acts on OPIOID RECEPTORS and is an analgesic. Its first four amino acids at the N-terminal are identical to the tetrapeptide sequence of METHIONINE ENKEPHALIN and LEUCINE ENKEPHALIN.. beta-endorphin : A polypeptide consisting of 31 amino acid residues in the sequence Tyr-Gly-Gly-Phe-Met-Thr-Ser-Glu-Lys-Ser-Gln-Thr-Pro-Leu-Val-Thr-Leu-Phe-Lys-Asn-Ala-Ile-Ile-Lys-Asn-Ala-Tyr-Lys-Lys-Gly-Glu. It is an endogenous opioid peptide neurotransmitter found in the neurons of both the central and peripheral nervous system and results from processing of the precursor protein proopiomelanocortin (POMC).		2.1710
oligonucleotides
[no description available]		11.761510
cellulose
DEAE-Cellulose: Cellulose derivative used in chromatography, as ion-exchange material, and for various industrial applications.		10.7832glycoside
phosphatidylcholines
Phosphatidylcholines: Derivatives of PHOSPHATIDIC ACIDS in which the phosphoric acid is bound in ester linkage to a CHOLINE moiety.		2.93401,2-diacyl-sn-glycero-3-phosphocholine
gdc-0973
cobimetinib: has antineoplastic activity; structure in first source. cobimetinib : A member of the class of N-acylazetidines obtained by selective formal condensation of the carboxy group of 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoic acid with the secondary amino group from the azetidine ring of 3-[(2S)-piperidin-2-yl]azetidin-3-ol. An inhibitor of mitogen-activated protein kinase that is used (as its fumarate salt) in combination with vemurafenib for the treatment of patients with unresectable or metastatic melanoma.		3.3110aromatic amine;
difluorobenzene;
N-acylazetidine;
organoiodine compound;
piperidines;
secondary amino compound;
tertiary alcohol		antineoplastic agent;
EC 2.7.11.24 (mitogen-activated protein kinase) inhibitor
buparlisib
NVP-BKM120: a pan class I PI3 kinase inhibitor with antineoplastic activity; structure in first source		7.2553aminopyridine;
aminopyrimidine;
morpholines;
organofluorine compound		antineoplastic agent;
EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
4-thiouridylic acid
[no description available]		2.1110
chlorophyll a
Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms.. chlorophyll : A family of magnesium porphyrins, defined by the presence of a fifth ring beyond the four pyrrole-like rings. The rings can have various side chains which usually include a long phytol chain.		3.0140chlorophyll;
methyl ester		cofactor
pevonedistat
pevonedistat: a potent and selective inhibitor of NAE (NEDD8-activating enzyme). pevonedistat : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine which is substituted by a (1S)-2,3-dihydro-1H-inden-1-ylnitrilo group at position 4 and by a (1S,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl group at position 7. It is a potent and selective NEDD8-activating enzyme inhibitor with an IC50 of 4.7 nM, and currently under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes.		4.4641cyclopentanols;
indanes;
pyrrolopyrimidine;
secondary amino compound;
sulfamidate		antineoplastic agent;
apoptosis inducer
ku 0063794
Ku 0063794: an mTOR inhibitor; structure in first source		2.110benzyl alcohols;
monomethoxybenzene;
morpholines;
pyridopyrimidine;
tertiary amino compound		antineoplastic agent;
mTOR inhibitor
sphingosine kinase
[no description available]		2.0210
calpain
Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4.		7.730
chitosan
[no description available]		6.0881
icotinib
[no description available]		8.9330
2-fluoro-araatp
[no description available]		2.0210
mesna
Mesna: A sulfhydryl compound used to prevent urothelial toxicity by inactivating metabolites from ANTINEOPLASTIC AGENTS, such as IFOSFAMIDE or CYCLOPHOSPHAMIDE.		13.465730organosulfonic acid
sodium pertechnetate tc 99m
Sodium Pertechnetate Tc 99m: A gamma-emitting radionuclide imaging agent used for the diagnosis of diseases in many tissues, particularly in the gastrointestinal system, cardiovascular and cerebral circulation, brain, thyroid, and joints.		1.9810
cortisol succinate, sodium salt
hydrocortisone hemisuccinate: RN given refers to (11beta)-isomer; Synonyms Solu-Cortef & sopolcort H refer to Na salt		1.9710organic molecular entity
arginine
Teniposide: A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Teniposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent cells from entering into the mitotic phase of the cell cycle, and lead to cell death. Teniposide acts primarily in the G2 and S phases of the cycle.. teniposide : A furonaphthodioxole that is a synthetic derivative of podophyllotoxin with anti-tumour activity; causes single- and double-stranded breaks in DNA and DNA-protein cross-links and prevents repair by topoisomerase II binding.		11.853018
olaparib
[no description available]		13.453612cyclopropanes;
monofluorobenzenes;
N-acylpiperazine;
phthalazines		antineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor
thiostrepton
Thiostrepton: One of the CYCLIC PEPTIDES from Streptomyces that is active against gram-positive bacteria. In veterinary medicine, it has been used in mastitis caused by gram-negative organisms and in dermatologic disorders.. thiostrepton : A heterodetic cyclic peptide, in which the cyclisation step involves a formal lactonisation between the carboxy group of a quinaldic acid-based residue and a secondary alcohol. An antibiotic that inhibits bacterial protein synthesis. Also acts as an antitumor agent.		7.110
mln 8237
MLN 8237: an aurora kinase A inhibitor		2.2110benzazepine
bms 754807
BMS 754807: an IGR-1R kinase inhibitor; structure in first source		2.1310pyrazoles;
pyridines;
pyrrolidines;
pyrrolotriazine		antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
gdc-0068
ipatasertib: an Akt kinase inhibitor; structure in first source		4.421N-arylpiperazine
delanzomib
[no description available]		2.1710C-terminal boronic acid peptide;
phenylpyridine;
secondary alcohol;
threonine derivative		antineoplastic agent;
apoptosis inducer;
proteasome inhibitor
pci 32765
ibrutinib: a Btk protein inhibitor. ibrutinib : A member of the class of acrylamides that is (3R)-3-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine in which the piperidine nitrogen is replaced by an acryloyl group. A selective and covalent inhibitor of the enzyme Bruton's tyrosine kinase, it is used for treatment of B-cell malignancies.		5.5522acrylamides;
aromatic amine;
aromatic ether;
N-acylpiperidine;
pyrazolopyrimidine;
tertiary carboxamide		antineoplastic agent;
EC 2.7.10.2 (non-specific protein-tyrosine kinase) inhibitor
ethyl cellulose
[no description available]		3.8121glycoside
mk-1775
adavosertib: a Wee1 kinase inhibitor; structure in first source		7.654piperazines
niraparib
niraparib: structure in first source. niraparib : A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy.		7.07322-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamideantineoplastic agent;
apoptosis inducer;
EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor;
radiosensitizing agent
mk 2206
MK 2206: a protein kinase inhibitor and antineoplastic agent		5.341organic heterotricyclic compoundEC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor
navitoclax
[no description available]		10.1131aryl sulfide;
monochlorobenzenes;
morpholines;
N-sulfonylcarboxamide;
organofluorine compound;
piperazines;
secondary amino compound;
sulfone;
tertiary amino compound		antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
egg white
Egg White: The white of an egg, especially a chicken's egg, used in cooking. It contains albumin. (Random House Unabridged Dictionary, 2d ed)		2.4720
4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
[no description available]		2.2510BODIPY compound
oprozomib
ONX 0912: antineoplastic; an orally active proteasome inhibitor; structure in first source		2.1710
ly2510924
LY2510924: a CXCR4 antagonist		9.4511
ixazomib
ixazomib: a proteasome inhibitor with antineoplastic activity; MLN2238 is the biologically active form of MLN9708; structure in first source. ixazomib : A glycine derivative that is the amide obtained by formal condensation of the carboxy group of N-(2,5-dichlorobenzoyl)glycine with the amino group of [(1R)-1-amino-3-methylbutyl]boronic acid. The active metabolite of ixazomib citrate, it is used in combination therapy for treatment of multiple myeloma.		9.8821benzamides;
boronic acids;
dichlorobenzene;
glycine derivative		antineoplastic agent;
apoptosis inducer;
drug metabolite;
orphan drug;
proteasome inhibitor
fit-039
FIT-039: CDK9 inhibitor; structure in first source		2.2110
plx4032
[no description available]		3.3110aromatic ketone;
difluorobenzene;
monochlorobenzenes;
pyrrolopyridine;
sulfonamide		antineoplastic agent;
B-Raf inhibitor
gsk 1363089
GSK 1363089: a multikinase inhibitor that acts on Met, RON, Axl, and VEGFR; structure in first source		2.2110aromatic ether
glycolipids
[no description available]		4.6111
elafin
Elafin: A secretory proteinase inhibitory protein that was initially purified from human SKIN. It is found in a variety mucosal secretions and is present at high levels in SPUTUM. Elafin may play a role in the innate immunity (IMMUNITY, INNATE) response of the LUNG.		2.4110
piperidines
Piperidines: A family of hexahydropyridines.		12.192214
thymosin
Thymosin: Thymosin. A family of heat-stable, polypeptide hormones secreted by the thymus gland. Their biological activities include lymphocytopoiesis, restoration of immunological competence and enhancement of expression of T-cell characteristics and function. They have therapeutic potential in patients having primary or secondary immunodeficiency diseases, cancer or diseases related to aging.		3.411
interleukin-8
Interleukin-8: A member of the CXC chemokine family that plays a role in the regulation of the acute inflammatory response. It is secreted by variety of cell types and induces CHEMOTAXIS of NEUTROPHILS and other inflammatory cells.		6.0581
dabrafenib
[no description available]		3.73201,3-thiazoles;
aminopyrimidine;
organofluorine compound;
sulfonamide		anticoronaviral agent;
antineoplastic agent;
B-Raf inhibitor
pki 587
gedatolisib: inhibits both phosphatidylinositol 3-kinase and mTOR; structure in first source		3.711
ribociclib
ribociclib: inhibits both CDK4 and CDK6		4.7211
apatinib
apatinib: reverses multidrug resistance by inhibiting the efflux function of multiple ATP-binding cassette transporters; structure in first source		5.6841
mk-8033
1-(3-(1-methyl-1H-pyrazol-4-yl)-5-oxo-5H-benzo(4,5)cyclohepta(1,2-b)pyridin-7-yl)-N-(pyridin-2-ylmethyl)methanesulfonamide: inhibits both Ron and c-Met kinases; structure in first source		7.0810
gx 15-070
obatoclax: a pan-Bcl-2 inhibitor potentially useful in treating mantle cell lymphoma		5.6332
5-(4-amino-1-propan-2-yl-3-pyrazolo[3,4-d]pyrimidinyl)-1,3-benzoxazol-2-amine
sapanisertib: an mTOR inhibitor		4.6111benzoxazole
bay 1000394
roniciclib: an antineoplastic agent that inhibits cyclin-dependent kinases; structure in first source		4.9221
14-o-phosphonooxymethyltriptolide
14-O-phosphonooxymethyltriptolide disodium salt: pro-drug of triptolide; has antineoplastic activity		2.110
afuresertib
[no description available]		9.5111amphetamines
birinapant
birinapant: a Smac mimetic with antineoplastic activity		7.5920dipeptide
abt-199
venetoclax: A BCL-2 inhibitor with antineoplastic activity that is used in the treatment of CHRONIC LYMPHOCYTIC LEUKEMIA associated with chromosome 17p deletion; structure in first source.. venetoclax : A member of the class of pyrrolopyridines that is a potent inhibitor of the antiapoptotic protein B-cell lymphoma 2. It is used for treamtment of chronic lymphocytic leukemia with 17p deletion.		2.1310aromatic ether;
C-nitro compound;
monochlorobenzenes;
N-alkylpiperazine;
N-arylpiperazine;
N-sulfonylcarboxamide;
oxanes;
pyrrolopyridine		antineoplastic agent;
apoptosis inducer;
B-cell lymphoma 2 inhibitor
encorafenib
encorafenib: a BRAF inhibitor		2.2510
heme
Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.. ferroheme : Any iron(II)--porphyrin coordination complex.. ferroheme b : Heme b in which the iron has oxidation state +2.. heme : A heme is any tetrapyrrolic chelate of iron.		11.7132
ascorbic acid
Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.. L-ascorbic acid : The L-enantiomer of ascorbic acid and conjugate acid of L-ascorbate.. L-ascorbate : The L-enantiomer of ascorbate and conjugate base of L-ascorbic acid, arising from selective deprotonation of the 3-hydroxy group. Required for a range of essential metabolic reactions in all animals and plants.. vitamin C : Any member of a group of vitamers that belong to the chemical structural class called butenolides that exhibit biological activity against vitamin C deficiency in animals. The vitamers include L-ascorbic acid and its salt, ionized and oxidized forms.		7.4273ascorbic acid;
vitamin C		coenzyme;
cofactor;
flour treatment agent;
food antioxidant;
food colour retention agent;
geroprotector;
plant metabolite;
skin lightening agent
tetracycline
Tetracycline: A naphthacene antibiotic that inhibits AMINO ACYL TRNA binding during protein synthesis.. tetracycline : A broad-spectrum polyketide antibiotic produced by the Streptomyces genus of actinobacteria.		1.9710
minocycline
Minocycline: A TETRACYCLINE analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant STAPHYLOCOCCUS infections.. minocycline : A tetracycline analogue having a dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5.		1.9910
piroxicam
[no description available]		5.73102benzothiazine;
monocarboxylic acid amide;
pyridines		analgesic;
antirheumatic drug;
cyclooxygenase 1 inhibitor;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
non-steroidal anti-inflammatory drug
mobic
Meloxicam: A benzothiazine and thiazole derivative that acts as a NSAID and cyclooxygenase-2 (COX-2) inhibitor. It is used in the treatment of RHEUMATOID ARTHRITIS; OSTEOARTHRITIS; and ANKYLOSING SPONDYLITIS.. meloxicam : A benzothiazine that is piroxicam in which the pyridin-2-yl group is replaced by a 5-methyl-1,3-thiazol-2-yl group. A non-steroidal anti-inflammatory drug and selective inhibitor of COX-2, it is used particularly for the management of rheumatoid arthritis.		4.45411,3-thiazoles;
benzothiazine;
monocarboxylic acid amide		analgesic;
antirheumatic drug;
cyclooxygenase 2 inhibitor;
non-steroidal anti-inflammatory drug
warfarin
Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.. warfarin : A racemate comprising equal amounts of (R)- and (S)-warfarin. Extensively used as both an anticoagulant drug and as a pesticide against rats and mice.. 4-hydroxy-3-(3-oxo-1-phenylbutyl)-1-benzopyran-2-one : A member of the class of coumarins that is 4-hydroxycoumarin which is substituted at position 3 by a 1-phenyl-3-oxo-1-butyl group.		9.3960benzenes;
hydroxycoumarin;
methyl ketone
gimeracil
gimeracil: a biochemical and pharmacological modulator of 5-FU		2.0810organic molecular entity
6-o-palmitoylascorbic acid
[no description available]		210fatty acid ester
vulpinic acid
vulpinic acid: RN given refers to cpd without isomeric designation; structure given in first source; vulpinic acid refers to (E)-isomer		2.4110butenolide
ark 62-62
ARK 62-62: structure given in first source; RN given is for L-ascorbic acid, (SP-4-2) isomer		1.9610
s 1 (combination)
S 1 (combination): consists of tegafur, 5-chloro-2,4-dihydroxyuridine & potassium oxonate; an inhibitor of fluorouracil(5-FU) degradation; prolongs the blood 5-FU level as well as increases selective toxicity to tumor; used for the treatment of colon cancer		11.653819
nk 121
NK 121: structure given in first source		9.57296
carboxyphthalato-1,2-diaminocyclohexaneplatinum
carboxyphthalato-1,2-diaminocyclohexaneplatinum: RN given refers to hydrogen(SP-4-3(1R-trans))-isomer; structure		6.9371
epidermal growth factor
Epidermal Growth Factor: A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.		11.8371
pf 3512676
ProMune: an anticancer adjuvant and immunostimulant		5.0533
zhengguangmycin
zhengguangmycin: antitumor antibiotic complex consisting of more than 10 components; produced by Streptomyces pingyangensis;		2.0210
microcystin
microcystin: microcystins have the general structure cyclo(D-Ala-L-X-D-erythro--methylisoasp-L-Y-Adda-D-isoGlu-N-methyldehydroAla) where X and Y are variable L-amino acids;. microcystin : A family of cyclic heptapeptide hepatotoxins produced by a number of cyanobacteria, the most notable of which is Microcystis, from which the name of the family is derived. Microcystins consist of a heptapeptide macrocycle made up of five non-protein amino acids and two protein amino acids.		1.9910peptide
transforming growth factor beta
Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.		3.5780
cc-115
1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin-2(1H)-one: an mTOR kinase inhibitor; structure in first source		7.4110
n2-(1h-indazole-5-yl)-n6-methyl-3-nitropyridine-2,6-diamine
N2-(1H-indazole-5-yl)-N6-methyl-3-nitropyridine-2,6-diamine: a heat shock factor 1 antagonist; structure in first source. KRIBB11 : A member of the class of indazoles that is 1H-indazole substituted by a [6-(methylamino)-3-nitropyridin-2-yl]amino group at position 5. It is an inhibitor of heat shock factor 1 (IC50 = 1.2muM) and suppresses tumour growth in mouse xenograft models.		2.2110
acovenoside a
acovenoside A: Maasai arrow poison from Acokanthera schimperi; RN given refers to(1beta,3beta,5beta)-isomer; structure given in first source. acovenoside A : A cardenolide glycoside that is the 3-(6-deoxy-3-O-methyl-alpha-L-taloside) of 1beta,3beta,14-trihydroxy-5beta-card-20(22)-enolide.		7.610
selinexor
selinexor: inhibits karyopherin XPO1		5.6322
osimertinib
osimertinib: an EGFR tyrosine kinase inhibitor. osimertinib : A member of the class of aminopyrimidines that is 4-(1-methylindol-3-yl)pyrimidin-2-amine in which one of the amino hydrogens is replaced by a 2-methoxy-4-[2-(dimethylamino)ethyl](methyl)amino-5-acrylamidophenyl group. Used (as the mesylate salt) for treatment of EGFR T790M mutation positive non-small cell lung cancer.		11.11149acrylamides;
aminopyrimidine;
biaryl;
indoles;
monomethoxybenzene;
secondary amino compound;
secondary carboxamide;
substituted aniline;
tertiary amino compound		antineoplastic agent;
epidermal growth factor receptor antagonist
agar
Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis.. agar : A complex mixture of polysaccharides extracted from species of red algae. Its two main components are agarose and agaropectin. Agarose is the component responsible for the high-strength gelling properties of agar, while agaropectin provides the viscous properties.		2.7730
gsk-j4
GSK-J4: a JMJD3 inhibitor; structure in first source		2.1510organonitrogen heterocyclic compound
imetelstat
[no description available]		10.79109
glutaminase
[no description available]		2.0110
cyclin d1
Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.		5.7361
nuc-1031
NUC-1031: structure in first source		8.711
ter 286
TER 286: a glutathione-based glutathione S-transferase-activated cytotoxin; TLK-286 is the ((R)-(-))-isomer		3.4311
technetium tc 99m sulfur colloid
Technetium Tc 99m Sulfur Colloid: A gamma-emitting radionuclide imaging agent used for the diagnosis of diseases in many tissues, particularly in the gastrointestinal system, liver, and spleen.		3.5111
oligomycins
Oligomycins: A closely related group of toxic substances elaborated by various strains of Streptomyces. They are 26-membered macrolides with lactone moieties and double bonds and inhibit various ATPases, causing uncoupling of phosphorylation from mitochondrial respiration. Used as tools in cytochemistry. Some specific oligomycins are RUTAMYCIN, peliomycin, and botrycidin (formerly venturicidin X).		2.1310
kj-pyr-9
KJ-Pyr-9: antineoplastic; structure in first source		2.4110
carubicin
Carubicin: A very toxic anthracycline-type antineoplastic related to DAUNORUBICIN, obtained from Actinomadura carminata.. carminomycin(1+) : An anthracyline cation that is the conjugate acid of carminomycin, obtained by protonation of the amino group.		3.0610anthracycline cation
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone: an interleukin-1beta converting enzyme (ICE)-like protease inhibitor		2.0710
nitrophenols
Nitrophenols: PHENOLS carrying nitro group substituents.		3.76100
lewis x antigen
Lewis X Antigen: A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, Lewis X antigen is a stage-specific embryonic antigen.		3.3711
aqua regia
aqua regia: mixture of hydrochloric & nitric acids		2.110
angiotensin i
Angiotensin I: A decapeptide that is cleaved from precursor angiotensinogen by RENIN. Angiotensin I has limited biological activity. It is converted to angiotensin II, a potent vasoconstrictor, after the removal of two amino acids at the C-terminal by ANGIOTENSIN CONVERTING ENZYME.. angiotensin I : A ten amino acid peptide formed by renin cleavage of angiotensinogen. Angiotensin I has no direct biological function except that high levels can stimulate catecholamine production. It is metabolized to its biologically active byproduct angiotensin II, a potent vasoconstrictor, by angiotensin converting enzyme (ACE) through cleavage of the two terminal amino acids.. angiotensin I dizwitterion : A peptide zwitterion that is the dizwitterionic form of angiotensin I having both carboxy groups deprotonated and the aspartyl amino group and arginine side-chain protonated. It is the major species at pH 7.3.		3.4711angiotensin;
peptide zwitterion		human metabolite;
neurotransmitter agent
ferric oxide, saccharated
Ferric Oxide, Saccharated: A glucaric acid-iron conjugate that is used in the treatment of IRON-DEFICIENCY ANEMIA, including in patients with chronic kidney disease, when oral iron therapy is ineffective or impractical.		5.3322
hyaluronoglucosaminidase
Hyaluronoglucosaminidase: An enzyme that catalyzes the random hydrolysis of 1,4-linkages between N-acetyl-beta-D-glucosamine and D-glucuronate residues in hyaluronate. (From Enzyme Nomenclature, 1992) There has been use as ANTINEOPLASTIC AGENTS to limit NEOPLASM METASTASIS.		2.4320
apatorsen
apatorsen: an antisense oligonucleotide that targets Hsp27 for support of cancer therapy		8.5911
adrenomedullin
Adrenomedullin: A 52-amino acid peptide with multi-functions. It was originally isolated from PHEOCHROMOCYTOMA and ADRENAL MEDULLA but is widely distributed throughout the body including lung and kidney tissues. Besides controlling fluid-electrolyte homeostasis, adrenomedullin is a potent vasodilator and can inhibit pituitary ACTH secretion.		2.0710
epoetin alfa
Epoetin Alfa: A recombinant glycosylated form of erythropoietin which stimulates the differentiation and proliferation of erythroid precursors. It is used for the treatment of ANEMIA associated with CHRONIC RENAL FAILURE in dialysis and predialysis patients.		5.2343
vitamin b 12
Vitamin B 12: A cobalt-containing coordination compound produced by intestinal micro-organisms and found also in soil and water. Higher plants do not concentrate vitamin B 12 from the soil and so are a poor source of the substance as compared with animal tissues. INTRINSIC FACTOR is important for the assimilation of vitamin B 12.		4.0840
oblimersen
oblimersen: targets the Bcl-2 oncogene good efficacy with low toxicity tumour regressions		10.0333
cyclosporine
Cyclosporine: A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).		8.5189
silybin
Silybin: The major active component of silymarin flavonoids extracted from seeds of the MILK THISTLE, Silybum marianum; it is used in the treatment of HEPATITIS; LIVER CIRRHOSIS; and CHEMICAL AND DRUG INDUCED LIVER INJURY, and has antineoplastic activity; silybins A and B are diastereomers.		2.4220
lactoferrin
Lactoferrin: An iron-binding protein that was originally characterized as a milk protein. It is widely distributed in secretory fluids and is found in the neutrophilic granules of LEUKOCYTES. The N-terminal part of lactoferrin possesses a serine protease which functions to inactivate the TYPE III SECRETION SYSTEM used by bacteria to export virulence proteins for host cell invasion.		5.2831
digitonin
Digitonin: A glycoside obtained from Digitalis purpurea; the aglycone is digitogenin which is bound to five sugars. Digitonin solubilizes lipids, especially in membranes and is used as a tool in cellular biochemistry, and reagent for precipitating cholesterol. It has no cardiac effects.. digitonin : A spirostanyl glycoside that is digitogenin in which the 3-hydroxy group is substituted by a beta-D-glucopyranosyl-(1->3)-beta-D-galactopyranosyl-(1->2)-[beta-D-xylopyranosyl-(1->3)]-beta-D-glucopyranosyl-(1->4)-beta-D-galactopyranosyl group. It is a steroidal saponin isolated from the foxglove plant, Digitalis purpurea. It is used extensively as a mild non-ionic detergent for extracting proteins from membranes for structure and function studies.		6.9910
catalpol
catalpol: component of dihuang; RN given refers to (1aS-(1aalpha,1bbeta,2beta,5abeta,6beta,6aalpha))-isomer; RN for cpd without isomeric designation not avail 12/92		4.6111
muramidase
Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17.		3.4470
nedaplatin
nedaplatin: structure given in first source		13.81838
lewis y antigen
[no description available]		2.0610
sc002
SC002: structure in first source		4.0421
lutetium lu 177 dotatate
177Lu-DOTA-octreotate: an somatostatin receptor agonist		2.1110
exudates
Malaysia: A parliamentary democracy with a constitutional monarch in southeast Asia, consisting of 11 states (West Malaysia) on the Malay Peninsula and two states (East Malaysia) on the island of BORNEO. It is also called the Federation of Malaysia. Its capital is Kuala Lumpur. Before 1963 it was the Union of Malaya. It reorganized in 1948 as the Federation of Malaya, becoming independent from British Malaya in 1957 and becoming Malaysia in 1963 as a federation of Malaya, Sabah, Sarawak, and Singapore (which seceded in 1965). The form Malay- probably derives from the Tamil malay, mountain, with reference to its geography. (From Webster's New Geographical Dictionary, 1988, p715 & Room, Brewer's Dictionary of Names, 1992, p329)		4.1231
acyclovir
Acyclovir: A GUANOSINE analog that acts as an antimetabolite. Viruses are especially susceptible. Used especially against herpes.. acyclovir : An oxopurine that is guanine substituted by a (2-hydroxyethoxy)methyl substituent at position 9. Used in the treatment of viral infections.		2.41202-aminopurines;
oxopurine		antimetabolite;
antiviral drug
levoleucovorin
Levoleucovorin: A folate analog consisting of the pharmacologically active isomer of LEUCOVORIN.. (6S)-5-formyltetrahydrofolic acid : The pharmacologically active (6S)-stereoisomer of 5-formyltetrahydrofolic acid.		14.8776435-formyltetrahydrofolic acidantineoplastic agent;
metabolite
cyclic gmp
Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed). 3',5'-cyclic GMP : A 3',5'-cyclic purine nucleotide in which the purine nucleobase is specified as guanidine.		2.04103',5'-cyclic purine nucleotide;
guanyl ribonucleotide		Escherichia coli metabolite;
human metabolite;
mouse metabolite;
plant metabolite;
Saccharomyces cerevisiae metabolite
guanosine monophosphate
Guanosine Monophosphate: A guanine nucleotide containing one phosphate group esterified to the sugar moiety and found widely in nature.. guanosine 5'-monophosphate : A purine ribonucleoside 5'-monophosphate having guanine as the nucleobase.		7.730guanosine 5'-phosphate;
purine ribonucleoside 5'-monophosphate		biomarker;
Escherichia coli metabolite;
metabolite;
mouse metabolite
guanine
[no description available]		25.2199922-aminopurines;
oxopurine;
purine nucleobase		algal metabolite;
Escherichia coli metabolite;
human metabolite;
mouse metabolite;
Saccharomyces cerevisiae metabolite
guanosine
ribonucleoside : Any nucleoside where the sugar component is D-ribose.		2.420guanosines;
purines D-ribonucleoside		fundamental metabolite
hypoxanthine
[no description available]		2.0710nucleobase analogue;
oxopurine;
purine nucleobase		fundamental metabolite
folic acid
folcysteine: used to promote fertility in chickens. vitamin B9 : Any B-vitamin that exhibits biological activity against vitamin B9 deficiency. Vitamin B9 refers to the many forms of folic acid and its derivatives, including tetrahydrofolic acid (the active form), methyltetrahydrofolate (the primary form found in blood), methenyltetrahydrofolate, folinic acid amongst others. They are present in abundance in green leafy vegetables, citrus fruits, and animal products. Lack of vitamin B9 leads to anemia, a condition in which the body cannot produce sufficient number of red blood cells. Symptoms of vitamin B9 deficiency include fatigue, muscle weakness, and pale skin.		7.42141folic acids;
N-acyl-amino acid		human metabolite;
mouse metabolite;
nutrient
pheophytin a
pheophytin a: structure given in first source; RN given refers to (3S-(3alpha(2E,7S*,11S*),4beta,21beta))-isomer		2.2510
clozapine
Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with administration of this agent.. clozapine : A benzodiazepine that is 5H-dibenzo[b,e][1,4]diazepine substituted by a chloro group at position 8 and a 4-methylpiperazin-1-yl group at position 11. It is a second generation antipsychotic used in the treatment of psychiatric disorders like schizophrenia.		2.4820benzodiazepine;
N-arylpiperazine;
N-methylpiperazine;
organochlorine compound		adrenergic antagonist;
dopaminergic antagonist;
EC 3.4.21.26 (prolyl oligopeptidase) inhibitor;
environmental contaminant;
GABA antagonist;
histamine antagonist;
muscarinic antagonist;
second generation antipsychotic;
serotonergic antagonist;
xenobiotic
dacarbazine
(E)-dacarbazine : A dacarbazine in which the N=N double bond adopts a trans-configuration.		15.558523dacarbazine
didanosine
Didanosine: A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by a hydrogen. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. Didanosine is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA by binding to reverse transcriptase; ddI is then metabolized to dideoxyadenosine triphosphate, its putative active metabolite.. didanosine : A purine 2',3'-dideoxyribonucleoside that is inosine in which the hydroxy groups at both the 2' and the 3' positions on the sugar moiety have been replaced by hydrogen. An antiviral drug, it is used as a medication to treat HIV/AIDS.		2.0210purine 2',3'-dideoxyribonucleosideantimetabolite;
antiviral drug;
EC 2.4.2.1 (purine-nucleoside phosphorylase) inhibitor;
geroprotector;
HIV-1 reverse transcriptase inhibitor
ganciclovir
[no description available]		2.41102-aminopurines;
oxopurine		antiinfective agent;
antiviral drug
olanzapine
Olanzapine: A benzodiazepine derivative that binds SEROTONIN RECEPTORS; MUSCARINIC RECEPTORS; HISTAMINE H1 RECEPTORS; ADRENERGIC ALPHA-1 RECEPTORS; and DOPAMINE RECEPTORS. It is an antipsychotic agent used in the treatment of SCHIZOPHRENIA; BIPOLAR DISORDER; and MAJOR DEPRESSIVE DISORDER; it may also reduce nausea and vomiting in patients undergoing chemotherapy.. olanzapine : A benzodiazepine that is 10H-thieno[2,3-b][1,5]benzodiazepine substituted by a methyl group at position 2 and a 4-methylpiperazin-1-yl group at position 4.		7.0998benzodiazepine;
N-arylpiperazine;
N-methylpiperazine		antiemetic;
dopaminergic antagonist;
histamine antagonist;
muscarinic antagonist;
second generation antipsychotic;
serotonergic antagonist;
serotonin uptake inhibitor
raltitrexed
[no description available]		3.5320N-acyl-amino acid
8-hydroxyguanosine
8-hydroxyguanosine: immunostimulant for B lymphocytes; structure given in first source		2.0310purine nucleoside
pemetrexed
pemetrexed disodium : An organic sodium salt that is the disodium salt of N-{4-[2-(2-amino-4-oxo-4,7-dihydro-1H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-L-glutamic acid. Inhibits thymidylate synthase (TS), 421 dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT).		22.97412196N-acyl-L-glutamic acid;
pyrrolopyrimidine		antimetabolite;
antineoplastic agent;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
EC 2.1.1.45 (thymidylate synthase) inhibitor;
EC 2.1.2.2 (phosphoribosylglycinamide formyltransferase) inhibitor
tirapazamine
Tirapazamine: A triazine derivative that introduces breaks into DNA strands in hypoxic cells, sensitizing tumor cells to the cytotoxic activity of other drugs and radiation.. tirapazamine : A member of the class of benzotriazines that is 1,2,4-benzotriazine carrying an amino substituent at position 3 and two oxido substituents at positions 1 and 4.		8.8884aromatic amine;
benzotriazines;
N-oxide		antibacterial agent;
antineoplastic agent;
apoptosis inducer
sildenafil citrate
Sildenafil Citrate: A PHOSPHODIESTERASE TYPE-5 INHIBITOR; VASODILATOR AGENT and UROLOGICAL AGENT that is used in the treatment of ERECTILE DYSFUNCTION and PRIMARY PULMONARY HYPERTENSION.. sildenafil citrate : The citrate salt of sildenafil.		2.1110citrate saltEC 3.1.4.35 (3',5'-cyclic-GMP phosphodiesterase) inhibitor;
vasodilator agent
aprepitant
Aprepitant: A morpholine neurokinin-1 (NK1) receptor antagonist that is used in the management of nausea and vomiting caused by DRUG THERAPY, and for the prevention of POSTOPERATIVE NAUSEA AND VOMITING.. aprepitant : A morpholine-based antiemetic, which is or the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy. Aprepitant is a selective high-affinity antagonist of human substance P/neurokinin 1 (NK1) receptors.		10.522516(trifluoromethyl)benzenes;
cyclic acetal;
morpholines;
triazoles		antidepressant;
antiemetic;
neurokinin-1 receptor antagonist;
peripheral nervous system drug;
substance P receptor antagonist
fosaprepitant
fosaprepitant: a pro-drug form of aprepitant. fosaprepitant : A morpholine derivative that is the (1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ether of (3-{[(2R,3S)-3-(4-fluorophenyl)-2-hydroxymorpholin-4-yl]methyl}-5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)phosphonic acid.		5.4622(trifluoromethyl)benzenes;
cyclic acetal;
morpholines;
phosphoramide;
triazoles		antiemetic;
neurokinin-1 receptor antagonist;
prodrug
trypan blue
Trypan Blue: A diazo-naphthalene sulfonate that is widely used as a stain.. trypan blue : An organosulfonate salt that is the tetrasodium salt of 3,3'-[(3,3'-dimethylbiphenyl-4,4'-diyl)didiazene-2,1-diyl]bis(5-amino-4-hydroxynaphthalene-2,7-disulfonic acid).		2.4320
nintedanib
nintedanib : A member of the class of oxindoles that is a kinase inhibitor used (in the form of its ethylsulfonate salt) for the treatment of idiopathic pulmonary fibrosis and cancer.		10.491210
deoxydiguanosine diphosphosphate
5'-d(pGpG)-3' : A single-stranded DNA oligonucleotide comprising two 2'-deoxyguanosine residues connected by a 3'->5 linkage and with a phosphoric group at the 5'-terminus.		2105'-phospho-(3'->5')-dinucleotide;
single-stranded DNA oligonucleotide		Mycoplasma genitalium metabolite
methylnitronitrosoguanidine
Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.. N-methyl-N'-nitro-N-nitrosoguanidine : An N-nitroguanidine compound having nitroso and methyl substituents at the N'-position		1.9910nitroso compoundalkylating agent
8-hydroxy-2'-deoxyguanosine
8-Hydroxy-2'-Deoxyguanosine: Common oxidized form of deoxyguanosine in which C-8 position of guanine base has a carbonyl group.. 8-hydroxy-2'-deoxyguanosine : Guanosine substituted at the purine 8-position by a hydroxy group. It is used as a biomarker of oxidative DNA damage.		3.4411guanosinesbiomarker
amg531
[no description available]		6.9943
divicine
divicine: RN given refers to parent cpd		6.9810
cyclic guanosine monophosphate-adenosine monophosphate
2'-3'-cGAMP : A cyclic purine dinucleotide that consists of AMP and GMP units cyclised via 3',5'- and 2',5'-linkages respectively.		2.2110adenyl ribonucleotide;
cyclic purine dinucleotide;
guanyl ribonucleotide
sta 9090
[no description available]		2.5420ring assembly;
triazoles
bmn 673
talazoparib: inhibits both PARP1 and PARP2; structure in first source		8.811
pp242
torkinib : A member of the class of pyrazolopyrimidines that is 1H-pyrazolo[3,4-d]pyrimidine substituted by isopropyl, 5-hydroxyindol-2-yl and amino groups at positions 1, 3 and 4 respectively. It is a potent inhibitor of mTOR and exhibits anti-cancer properties.		2.110aromatic amine;
biaryl;
hydroxyindoles;
phenols;
primary amino compound;
pyrazolopyrimidine		antineoplastic agent;
mTOR inhibitor
eye
[no description available]		9.3241
acetylcellulose
acetylcellulose: coating compound. cellulose acetate : A glucan derivative obtained through the esterification of cellulose by acetic anhydride or acetic acid, resulting in the substitution of some of the hydroxy groups of cellulose by acetyl groups. It is used in a variety of applications including base material for photographic film, clothing, membrane filters, coatings, food packaging, and as a frame material for eyeglasses.		4.6111
concanavalin a
Concanavalin A: A MANNOSE/GLUCOSE binding lectin isolated from the jack bean (Canavalia ensiformis). It is a potent mitogen used to stimulate cell proliferation in lymphocytes, primarily T-lymphocyte, cultures.		1.9810
metallothionein
Metallothionein: A low-molecular-weight (approx. 10 kD) protein occurring in the cytoplasm of kidney cortex and liver. It is rich in cysteinyl residues and contains no aromatic amino acids. Metallothionein shows high affinity for bivalent heavy metals.		4.79100
phosphorus radioisotopes
Phosphorus Radioisotopes: Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes.		1.9810
nartograstim
nartograstim: a mutein of recombinant human G-CSF		3.3911
leptin
Leptin: A 16-kDa peptide hormone secreted from WHITE ADIPOCYTES. Leptin serves as a feedback signal from fat cells to the CENTRAL NERVOUS SYSTEM in regulation of food intake, energy balance, and fat storage.		2.2110
pyrimidinones
Pyrimidinones: Heterocyclic compounds known as 2-pyrimidones (or 2-hydroxypyrimidines) and 4-pyrimidones (or 4-hydroxypyrimidines) with the general formula C4H4N2O.		9.0794
phenanthrenes
Phenanthrenes: POLYCYCLIC AROMATIC HYDROCARBONS composed of three fused BENZENE rings.. phenanthrenes : Any benzenoid aromatic compound that consists of a phenanthrene skeleton and its substituted derivatives thereof.		2.7730
ConditionIndicatedRelationship StrengthStudiesTrials
Anemia, Fanconi
[description not available]		03.1450
Fanconi Anemia
Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)		08.1450
Congenital Zika Syndrome
[description not available]		02.2510
Disease Models, Animal
Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.		020.0220191
Zika Virus Infection
A viral disease transmitted by the bite of AEDES mosquitoes infected with ZIKA VIRUS. Its mild DENGUE-like symptoms include fever, rash, headaches and ARTHRALGIA. The viral infection during pregnancy, in rare cases, is associated with congenital brain and ocular abnormalities, called Congenital Zika Syndrome, including MICROCEPHALY and may also lead to GUILLAIN-BARRE SYNDROME.		02.2510
Cancer of Ovary
[description not available]		029.632,666943
Ovarian Neoplasms
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.		029.632,666943
Neoplasms, Cystic, Mucinous, and Serous
Neoplasms containing cyst-like formations or producing mucin or serum.		013.624816
Local Neoplasm Recurrence
[description not available]		027.541,395619
Deafness, Transitory
[description not available]		013.68685
Drug-Induced Cochlear Toxicity
[description not available]		06.97190
Ototoxicity
Damage to the EAR or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.		06.97190
Hearing Loss
A general term for the complete or partial loss of the ability to hear from one or both ears.		013.68685
Bladder Cancer
[description not available]		018.9125159
Urinary Bladder Neoplasms
Tumors or cancer of the URINARY BLADDER.		018.9125159
Carcinoma, Transitional Cell
A malignant neoplasm derived from TRANSITIONAL EPITHELIAL CELLS, occurring chiefly in the URINARY BLADDER; URETERS; or RENAL PELVIS.		018.3318152
Carcinoma, Non-Small Cell Lung
[description not available]		038.014,2493,121
Cancer of Lung
[description not available]		033.655,3503,499
Carcinoma, Non-Small-Cell Lung
A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.		033.014,2493,121
Lung Neoplasms
Tumors or cancer of the LUNG.		033.655,3503,499
Cancer of Liver
[description not available]		019.8825468
Liver Neoplasms
Tumors or cancer of the LIVER.		019.8825468
Hepatoblastoma
A malignant neoplasm occurring in young children, primarily in the liver, composed of tissue resembling embryonal or fetal hepatic epithelium, or mixed epithelial and mesenchymal tissues. (Stedman, 25th ed)		010.39328
Allergy, Drug
[description not available]		015.9616517
Pyrexia
[description not available]		09.984317
Female Genital Neoplasms
[description not available]		014.510840
Drug Hypersensitivity
Immunologically mediated adverse reactions to medicinal substances used legally or illegally.		020.9616517
Fever
An abnormal elevation of body temperature, usually as a result of a pathologic process.		014.984317
Genital Neoplasms, Female
Tumor or cancer of the female reproductive tract (GENITALIA, FEMALE).		014.510840
Malignant Melanoma
[description not available]		018.4715480
Cancer of Skin
[description not available]		016.2111127
Melanoma
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)		018.4715480
Skin Neoplasms
Tumors or cancer of the SKIN.		016.2111127
Cancer of Head
[description not available]		024.27574314
Head and Neck Neoplasms
Soft tissue tumors or cancer arising from the mucosal surfaces of the LIP; oral cavity; PHARYNX; LARYNX; and cervical esophagus. Other sites included are the NOSE and PARANASAL SINUSES; SALIVARY GLANDS; THYROID GLAND and PARATHYROID GLANDS; and MELANOMA and non-melanoma skin cancers of the head and neck. (from Holland et al., Cancer Medicine, 4th ed, p1651)		024.27574314
ER-Negative PR-Negative HER2-Negative Breast Cancer
[description not available]		023.88423313
Triple Negative Breast Neoplasms
Breast neoplasms that do not express ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and do not overexpress the NEU RECEPTOR/HER-2 PROTO-ONCOGENE PROTEIN.		023.88423313
Benign Neoplasms
[description not available]		023.94623253
Neoplasms
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.		023.94623253
Peritoneal Carcinomatosis
[description not available]		019.81281126
Cancer of the Fallopian Tube
[description not available]		018.7916790
Fallopian Tube Neoplasms
Benign or malignant neoplasms of the FALLOPIAN TUBES. They are uncommon. If they develop, they may be located in the wall or within the lumen as a growth attached to the wall by a stalk.		018.7916790
Peritoneal Neoplasms
Tumors or cancer of the PERITONEUM.		019.81281126
Epithelial Ovarian Cancer
[description not available]		023.07432176
Carcinoma, Ovarian Epithelial
A malignant neoplasm that originates in cells on the surface EPITHELIUM of the ovary and is the most common form of ovarian cancer. There are five histologic subtypes: papillary serous, endometrioid, mucinous, clear cell, and transitional cell. Mutations in BRCA1, OPCML, PRKN, PIK3CA, AKT1, CTNNB1, RRAS2, and CDH1 genes are associated with this cancer.		023.07432176
Cystadenocarcinoma, Serous
A malignant cystic or semicystic neoplasm. It often occurs in the ovary and usually bilaterally. The external surface is usually covered with papillary excrescences. Microscopically, the papillary patterns are predominantly epithelial overgrowths with differentiated and undifferentiated papillary serous cystadenocarcinoma cells. Psammoma bodies may be present. The tumor generally adheres to surrounding structures and produces ascites. (From Hughes, Obstetric-Gynecologic Terminology, 1972, p185)		017.0419842
Metastase
[description not available]		030.93733508
Neoplasm Metastasis
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.		025.93733508
Cancer of the Retina
[description not available]		015.5223932
Orbital Neoplasms
Neoplasms of the bony orbit and contents except the eyeball.		06.06101
Eye Cancer, Retinoblastoma
[description not available]		016.4129539
Retinoblastoma
A malignant tumor arising from the nuclear layer of the retina that is the most common primary tumor of the eye in children. The tumor tends to occur in early childhood or infancy and may be present at birth. The majority are sporadic, but the condition may be transmitted as an autosomal dominant trait. Histologic features include dense cellularity, small round polygonal cells, and areas of calcification and necrosis. An abnormal pupil reflex (leukokoria); NYSTAGMUS, PATHOLOGIC; STRABISMUS; and visual loss represent common clinical characteristics of this condition. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2104)		016.4129539
Cancer of Esophagus
[description not available]		025.69872744
Esophageal Neoplasms
Tumors or cancer of the ESOPHAGUS.		025.69872744
Thrombopenia
[description not available]		024.8656475
Emesis
[description not available]		018.55200103
Nausea
An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses.		019.13214118
Thrombocytopenia
A subnormal level of BLOOD PLATELETS.		024.8656475
Vomiting
The forcible expulsion of the contents of the STOMACH through the MOUTH.		018.55200103
Lung Adenocarcinoma
[description not available]		015.1110033
Adenocarcinoma of Lung
A carcinoma originating in the lung and the most common lung cancer type in never-smokers. Malignant cells exhibit distinct features such as glandular epithelial, or tubular morphology. Mutations in KRAS, EGFR, BRAF, and ERBB2 genes are associated with this cancer.		015.1110033
Carcinoma, Small Cell Lung
[description not available]		021.75327166
Small Cell Lung Carcinoma
A form of highly malignant lung cancer that is composed of small ovoid cells (SMALL CELL CARCINOMA).		021.75327166
Cancer of Cervix
[description not available]		020.3733099
Uterine Cervical Neoplasms
Tumors or cancer of the UTERINE CERVIX.		020.3733099
Retroperitoneal Neoplasms
New abnormal growth of tissue in the RETROPERITONEAL SPACE.		09.56316
Carcinoma, Neuroendocrine
A group of carcinomas which share a characteristic morphology, often being composed of clusters and trabecular sheets of round blue cells, granular chromatin, and an attenuated rim of poorly demarcated cytoplasm. Neuroendocrine tumors include carcinoids, small (oat) cell carcinomas, medullary carcinoma of the thyroid, Merkel cell tumor, cutaneous neuroendocrine carcinoma, pancreatic islet cell tumors, and pheochromocytoma. Neurosecretory granules are found within the tumor cells. (Segen, Dictionary of Modern Medicine, 1992)		013.46734
Cancer of Stomach
[description not available]		015.2810034
Stomach Neoplasms
Tumors or cancer of the STOMACH.		015.2810034
Benign Neoplasms, Brain
[description not available]		021.96485185
Brain Neoplasms
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.		021.96485185
Malignant Mesothelioma
[description not available]		015.48299
Canine Diseases
[description not available]		010.478014
Carcinoma, Epidermoid
[description not available]		026.711,269679
Carcinoma, Squamous Cell
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)		026.711,269679
Cancer, Embryonal
[description not available]		018.5417952
Cancer of Testis
[description not available]		019.8530664
Neoplasms, Germ Cell and Embryonal
Neoplasms composed of primordial GERM CELLS of embryonic GONADS or of elements of the germ layers of the EMBRYO, MAMMALIAN. The concept does not refer to neoplasms located in the gonads or present in an embryo or FETUS.		018.5417952
Testicular Neoplasms
Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms.		019.8530664
Esophageal Squamous Cell Carcinoma
A carcinoma that originates usually from cells on the surface of the middle and lower third of the ESOPHAGUS. Tumor cells exhibit typical squamous morphology and form large polypoid lesions. Mutations in RNF6, LZTS1, TGFBR2, DEC1, and WWOX1 genes are associated with this cancer.		012.663216
Mucositis, Oral
[description not available]		012.074128
Stomatitis
INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP.		012.074128
Carcinoma, Anaplastic
[description not available]		021.24374148
Carcinoma
A malignant neoplasm made up of epithelial cells tending to infiltrate the surrounding tissues and give rise to metastases. It is a histological type of neoplasm and not a synonym for cancer.		021.24374148
Neutropenia
A decrease in the number of NEUTROPHILS found in the blood.		024.52664528
Innate Inflammatory Response
[description not available]		013.232517
Inflammation
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.		018.232517
Carcinoma, Large Cell
A tumor of undifferentiated (anaplastic) cells of large size. It is usually bronchogenic. (From Dorland, 27th ed)		020.17268234
Complications, Neoplastic Pregnancy
[description not available]		08.25330
HPV Infection
[description not available]		014.897148
Carcinoma, Squamous Cell of Head and Neck
[description not available]		014.717721
Asthma, Bronchial
[description not available]		05.0931
Dysphagia
[description not available]		08.03185
Cancer of Larynx
[description not available]		011.856014
Hoarseness
An unnaturally deep or rough quality of voice.		02.3110
Squamous Cell Carcinoma of Head and Neck
The most common type of head and neck carcinoma that originates from cells on the surface of the NASAL CAVITY; MOUTH; PARANASAL SINUSES, SALIVARY GLANDS, and LARYNX. Mutations in TNFRSF10B, PTEN, and ING1 genes are associated with this cancer.		019.717721
Asthma
A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).		05.0931
Deglutition Disorders
Difficulty in SWALLOWING which may result from neuromuscular disorder or mechanical obstruction. Dysphagia is classified into two distinct types: oropharyngeal dysphagia due to malfunction of the PHARYNX and UPPER ESOPHAGEAL SPHINCTER; and esophageal dysphagia due to malfunction of the ESOPHAGUS.		08.03185
Laryngeal Neoplasms
Cancers or tumors of the LARYNX or any of its parts: the GLOTTIS; EPIGLOTTIS; LARYNGEAL CARTILAGES; LARYNGEAL MUSCLES; and VOCAL CORDS.		011.856014
Pregnancy
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.		015.488619
Papillomavirus Infections
Neoplasms of the skin and mucous membranes caused by papillomaviruses. They are usually benign but some have a high risk for malignant progression.		014.897148
Genetic Predisposition
[description not available]		013.784216
Nasopharyngeal Carcinoma
A carcinoma that originates in the EPITHELIUM of the NASOPHARYNX and includes four subtypes: keratinizing squamous cell, non-keratinizing, basaloid squamous cell, and PAPILLARY ADENOCARCINOMA. It is most prevalent in Southeast Asian populations and is associated with EPSTEIN-BARR VIRUS INFECTIONS. Somatic mutations associated with this cancer have been identified in NPCR, BAP1, UBAP1, ERBB2, ERBB3, MLL2, PIK3CA, KRAS, NRAS, and ARID1A genes.		09.87136
Cancer of Nasopharynx
[description not available]		014.966841
Nasopharyngeal Neoplasms
Tumors or cancer of the NASOPHARYNX.		014.966841
Germinoma
A malignant neoplasm of the germinal tissue of the GONADS; MEDIASTINUM; or pineal region. Germinomas are uniform in appearance, consisting of large, round cells with vesicular nuclei and clear or finely granular eosinophilic-staining cytoplasm. (Stedman, 265th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1642-3)		021.1412143
Adenocarcinoma, Endometrioid
[description not available]		014.517817
Adenocarcinoma, Basal Cell
[description not available]		027.261,4891,052
Adenocarcinoma
A malignant epithelial tumor with a glandular organization.		027.261,4891,052
Carcinoma, Endometrioid
An adenocarcinoma characterized by the presence of cells resembling the glandular cells of the ENDOMETRIUM. It is a common histological type of ovarian CARCINOMA and ENDOMETRIAL CARCINOMA. There is a high frequency of co-occurrence of this form of adenocarcinoma in both tissues.		014.517817
Breast Cancer
[description not available]		024.01601283
Breast Neoplasms
Tumors or cancer of the human BREAST.		024.01601283
Disease Exacerbation
[description not available]		026.61791589
Astrocytoma, Grade IV
[description not available]		015.9712080
Glioblastoma
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.		015.9712080
Cancer of the Uterus
[description not available]		015.4210122
Carcinosarcoma
A malignant neoplasm that contains elements of carcinoma and sarcoma so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue. (Stedman, 25th ed)		013.745111
Uterine Neoplasms
Tumors or cancer of the UTERUS.		015.4210122
Benign Cerebellar Neoplasms
[description not available]		012.745316
Arachnoidal Cerebellar Sarcoma, Circumscribed
[description not available]		012.786522
Medulloblastoma
A malignant neoplasm that may be classified either as a glioma or as a primitive neuroectodermal tumor of childhood (see NEUROECTODERMAL TUMOR, PRIMITIVE). The tumor occurs most frequently in the first decade of life with the most typical location being the cerebellar vermis. Histologic features include a high degree of cellularity, frequent mitotic figures, and a tendency for the cells to organize into sheets or form rosettes. Medulloblastoma have a high propensity to spread throughout the craniospinal intradural axis. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2060-1)		012.786522
Cholera Infantum
[description not available]		013.033419
Peripheral Nerve Diseases
[description not available]		015.417835
Cancer of Endometrium
[description not available]		019.2726871
Peripheral Nervous System Diseases
Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves.		015.417835
Endometrial Neoplasms
Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.		019.2726871
Genome Instability
[description not available]		011.351915
HBOC Syndrome
[description not available]		05.6822
Hereditary Breast and Ovarian Cancer Syndrome
Autosomal dominant HEREDITARY CANCER SYNDROME in which a mutation most often in either BRCA1 or BRCA2 is associated with a significantly increased risk for breast and ovarian cancers.		05.6822
Carcinoma, Adenosquamous
A mixed adenocarcinoma and squamous cell or epidermoid carcinoma.		010.86276
Lassitude
[description not available]		019.17155146
Chronic Insomnia
[description not available]		05.7232
Adverse Effects, Long Term
[description not available]		02.4110
Chemo-Fog
[description not available]		02.4110
Anxiety
Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS.		05.2362
Fatigue
The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.		019.17155146
Sleep Initiation and Maintenance Disorders
Disorders characterized by impairment of the ability to initiate or maintain sleep. This may occur as a primary disorder or in association with another medical or psychiatric condition.		05.7232
Adverse Drug Event
[description not available]		014.997039
Drug-Related Side Effects and Adverse Reactions
Disorders that result from the intended use of PHARMACEUTICAL PREPARATIONS. Included in this heading are a broad variety of chemically-induced adverse conditions due to toxicity, DRUG INTERACTIONS, and metabolic effects of pharmaceuticals.		014.997039
Cancer of Oropharnyx
[description not available]		015.759237
Oropharyngeal Neoplasms
Tumors or cancer of the OROPHARYNX.		015.759237
Adenopathy
[description not available]		02.6920
Tumour Lysis Syndrome
[description not available]		05.25111
Hepatic Failure
[description not available]		04.3741
Tumor Lysis Syndrome
A syndrome resulting from cytotoxic therapy, occurring generally in aggressive, rapidly proliferating lymphoproliferative disorders. It is characterized by combinations of hyperuricemia, lactic acidosis, hyperkalemia, hyperphosphatemia and hypocalcemia.		05.25111
Liver Failure
Severe inability of the LIVER to perform its normal metabolic functions, as evidenced by severe JAUNDICE and abnormal serum levels of AMMONIA; BILIRUBIN; ALKALINE PHOSPHATASE; ASPARTATE AMINOTRANSFERASE; LACTATE DEHYDROGENASES; and albumin/globulin ratio. (Blakiston's Gould Medical Dictionary, 4th ed)		09.3741
Glial Cell Tumors
[description not available]		018.1719571
Glioma
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)		018.1719571
Aneurysm, Thoracic Aortic
[description not available]		02.4110
Aortic Aneurysm, Thoracic
An abnormal balloon- or sac-like dilatation in the wall of the THORACIC AORTA. This proximal descending portion of aorta gives rise to the visceral and the parietal branches above the aortic hiatus at the diaphragm.		02.4110
Cancer of Prostate
[description not available]		016.0610236
Prostatic Neoplasms
Tumors or cancer of the PROSTATE.		016.0610236
Cancer of Kidney
[description not available]		015.58423
Bilateral Wilms Tumor
[description not available]		010.99385
Kidney Neoplasms
Tumors or cancers of the KIDNEY.		015.58423
Wilms Tumor
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.		010.99385
Minimal Disease, Residual
[description not available]		016.6910341
Cancer of Pancreas
[description not available]		015.736725
Pancreatic Neoplasms
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).		015.736725
Neoplasm Metastasis, Unknown Primary
[description not available]		013.225928
Chylopericardium
[description not available]		04.9181
Pericardial Effusion
Fluid accumulation within the PERICARDIUM. Serous effusions are associated with pericardial diseases. Hemopericardium is associated with trauma. Lipid-containing effusion (chylopericardium) results from leakage of THORACIC DUCT. Severe cases can lead to CARDIAC TAMPONADE.		04.9181
Dermatitis Medicamentosa
[description not available]		09.84246
Brill-Symmers Disease
[description not available]		03.3660
Diffuse Mixed Small and Large Cell Lymphoma
[description not available]		014.897129
Diffuse Large B-Cell Lymphoma
[description not available]		016.657952
Lymphoma, Follicular
Malignant lymphoma in which the lymphomatous cells are clustered into identifiable nodules within the LYMPH NODES. The nodules resemble to some extent the GERMINAL CENTER of lymph node follicles and most likely represent neoplastic proliferation of lymph node-derived follicular center B-LYMPHOCYTES.		03.3660
Lymphoma, Non-Hodgkin
Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.		014.897129
Lymphoma, Large B-Cell, Diffuse
Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation.		016.657952
Cerebral Primitive Neuroectodermal Tumor
[description not available]		010.332510
Neuroectodermal Tumors, Primitive
A group of malignant tumors of the nervous system that feature primitive cells with elements of neuronal and/or glial differentiation. Use of this term is limited by some authors to central nervous system tumors and others include neoplasms of similar origin which arise extracranially (i.e., NEUROECTODERMAL TUMORS, PRIMITIVE, PERIPHERAL). This term is also occasionally used as a synonym for MEDULLOBLASTOMA. In general, these tumors arise in the first decade of life and tend to be highly malignant. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2059)		010.332510
Wasting Disease
[description not available]		02.4110
Central Diabetes Insipidus
[description not available]		02.9640
Symptom Cluster
[description not available]		04.76110
Diabetes Mellitus
A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.		05.3241
Hyponatremia
Deficiency of sodium in the blood; salt depletion. (Dorland, 27th ed)		05.69102
Syndrome
A characteristic symptom complex.		09.76110
Diabetes Insipidus, Neurogenic
A genetic or acquired polyuric disorder caused by a deficiency of VASOPRESSINS secreted by the NEUROHYPOPHYSIS. Clinical signs include the excretion of large volumes of dilute URINE; HYPERNATREMIA; THIRST; and polydipsia. Etiologies include HEAD TRAUMA; surgeries and diseases involving the HYPOTHALAMUS and the PITUITARY GLAND. This disorder may also be caused by mutations of genes such as ARVP encoding vasopressin and its corresponding neurophysin (NEUROPHYSINS).		02.9640
Extranodal NK-T-Cell Lymphoma
[description not available]		07.58111
Blood Pressure, High
[description not available]		019.13128114
Hypertension
Persistently high systemic arterial BLOOD PRESSURE. Based on multiple readings (BLOOD PRESSURE DETERMINATION), hypertension is currently defined as when SYSTOLIC PRESSURE is consistently greater than 140 mm Hg or when DIASTOLIC PRESSURE is consistently 90 mm Hg or more.		019.13128114
Proteinuria
The presence of proteins in the urine, an indicator of KIDNEY DISEASES.		09.49172
Sister Joseph's Nodule
[description not available]		03.4520
Rhabdomyosarcoma
A malignant solid tumor arising from mesenchymal tissues which normally differentiate to form striated muscle. It can occur in a wide variety of sites. It is divided into four distinct types: pleomorphic, predominantly in male adults; alveolar (RHABDOMYOSARCOMA, ALVEOLAR), mainly in adolescents and young adults; embryonal (RHABDOMYOSARCOMA, EMBRYONAL), predominantly in infants and children; and botryoidal, also in young children. It is one of the most frequently occurring soft tissue sarcomas and the most common in children under 15. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p2186; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, pp1647-9)		010.1229
Rhabdomyosarcoma, Embryonal
A form of RHABDOMYOSARCOMA arising primarily in the head and neck, especially the orbit, of children below the age of 10. The cells are smaller than those of other rhabdomyosarcomas and are of two basic cell types: spindle cells and round cells. This cancer is highly sensitive to chemotherapy and has a high cure rate with multi-modality therapy. (From Holland et al., Cancer Medicine, 3d ed, p2188)		04.2160
Acute Kidney Failure
[description not available]		09.07424
Acute Kidney Injury
Abrupt reduction in kidney function. Acute kidney injury encompasses the entire spectrum of the syndrome including acute kidney failure; ACUTE KIDNEY TUBULAR NECROSIS; and other less severe conditions.		014.07424
Body Weight
The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.		011.93626
Neuroblastoma
A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)		017.0213740
Bone Cancer
[description not available]		017.0716243
Osteogenic Sarcoma
[description not available]		012.738519
Bone Neoplasms
Tumors or cancer located in bone tissue or specific BONES.		017.0716243
Osteosarcoma
A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed)		012.738519
Lymphoma, T Cell, Peripheral
[description not available]		08.29132
Lymphoma, T-Cell, Peripheral
A group of malignant lymphomas thought to derive from peripheral T-lymphocytes in lymph nodes and other nonlymphoid sites. They include a broad spectrum of lymphocyte morphology, but in all instances express T-cell markers admixed with epithelioid histiocytes, plasma cells, and eosinophils. Although markedly similar to large-cell immunoblastic lymphoma (LYMPHOMA, LARGE-CELL, IMMUNOBLASTIC), this group's unique features warrant separate treatment.		08.29132
Carcinogenesis
The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.		011.26179
Cells, Neoplasm Circulating
[description not available]		010.07306
Acute Myelogenous Leukemia
[description not available]		017.263618
Leukemia, Myeloid, Acute
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.		012.263618
Recrudescence
[description not available]		019.98208111
Diffuse Parenchymal Lung Disease
[description not available]		09.58258
Lung Diseases, Interstitial
A diverse group of lung diseases that affect the lung parenchyma. They are characterized by an initial inflammation of PULMONARY ALVEOLI that extends to the interstitium and beyond leading to diffuse PULMONARY FIBROSIS. Interstitial lung diseases are classified by their etiology (known or unknown causes), and radiological-pathological features.		09.58258
Cryptogenic Fibrosing Alveolitis
[description not available]		06.3262
Idiopathic Pulmonary Fibrosis
A common interstitial lung disease of unknown etiology, usually occurring between 50-70 years of age. Clinically, it is characterized by an insidious onset of breathlessness with exertion and a nonproductive cough, leading to progressive DYSPNEA. Pathological features show scant interstitial inflammation, patchy collagen fibrosis, prominent fibroblast proliferation foci, and microscopic honeycomb change.		06.3262
Polyploid
[description not available]		02.8330
Acquired Immune Deficiency Syndrome
[description not available]		05.4151
HIV Coinfection
[description not available]		09.76114
Acquired Immunodeficiency Syndrome
An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993.		05.4151
HIV Infections
Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).		09.76114
Germinoblastoma
[description not available]		013.014517
T-Cell Lymphoma
[description not available]		06.56101
Lymphoma
A general term for various neoplastic diseases of the lymphoid tissue.		013.014517
Lymphoma, T-Cell
A group of heterogeneous lymphoid tumors representing malignant transformations of T-lymphocytes.		06.56101
Diffuse Lymphocytic Lymphoma, Poorly-Differentiated
[description not available]		07.3553
Lymphoma, Mantle-Cell
A form of non-Hodgkin lymphoma having a usually diffuse pattern with both small and medium lymphocytes and small cleaved cells. It accounts for about 5% of adult non-Hodgkin lymphomas in the United States and Europe. The majority of mantle-cell lymphomas are associated with a t(11;14) translocation resulting in overexpression of the CYCLIN D1 gene (GENES, BCL-1).		07.3553
Plasmablastic Diffuse Large B-cell Lymphoma
[description not available]		02.4110
Pemphigoid
[description not available]		07.4110
Pemphigoid, Bullous
A chronic and relatively benign subepidermal blistering disease usually of the elderly and without histopathologic acantholysis.		02.4110
Cancer of Mouth
[description not available]		09.42587
Sarcoma, Epithelioid
[description not available]		012.985719
Cat Diseases
Diseases of the domestic cat (Felis catus or F. domesticus). This term does not include diseases of the so-called big cats such as CHEETAHS; LIONS; tigers, cougars, panthers, leopards, and other Felidae for which the heading CARNIVORA is used.		06.15162
Mouth Neoplasms
Tumors or cancer of the MOUTH.		09.42587
Sarcoma
A connective tissue neoplasm formed by proliferation of mesodermal cells; it is usually highly malignant.		012.985719
Endometrial Stromal Sarcoma
[description not available]		09.1431
Sarcoma, Endometrial Stromal
A highly malignant subset of neoplasms arising from the endometrial stroma. Tumors in this group infiltrate the stroma with a wide range of atypia cells and numerous mitoses. They are capable of widespread metastases (NEOPLASM METASTASIS).		04.1431
Cholangiocellular Carcinoma
[description not available]		07.5973
Bile Duct Cancer
[description not available]		07.7183
Hepatocellular Carcinoma
[description not available]		013.75414
Bile Duct Neoplasms
Tumors or cancer of the BILE DUCTS.		07.7183
Carcinoma, Hepatocellular
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.		013.75414
Cholangiocarcinoma
A malignant tumor arising from the epithelium of the BILE DUCTS.		012.5973
Anaphylactic Reaction
[description not available]		010.66181
Anaphylaxis
An acute hypersensitivity reaction due to exposure to a previously encountered ANTIGEN. The reaction may include rapidly progressing URTICARIA, respiratory distress, vascular collapse, systemic SHOCK, and death.		05.66181
Erythema
Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes.		04.8471
Seminoma
A radiosensitive, malignant neoplasm of the testis, thought to be derived from primordial germ cells of the sexually undifferentiated embryonic gonad. There are three variants: classical (typical), the most common type; anaplastic; and spermatocytic. The classical seminoma is composed of fairly well differentiated sheets or cords of uniform polygonal or round cells (seminoma cells), each cell having abundant clear cytoplasm, distinct cell membranes, a centrally placed round nucleus, and one or more nucleoli. In the female, a grossly and histologically identical neoplasm, known as dysgerminoma, occurs. (Dorland, 27th ed)		016.814123
Adult Fanconi Syndrome
[description not available]		02.4620
Chronic Illness
[description not available]		06.3172
Chronic Disease
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2).		06.3172
Anorexia
The lack or loss of APPETITE accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder ANOREXIA NERVOSA.		010.612012
Craniofacial Abnormalities
Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones.		02.4110
Cancer of the Urinary Tract
[description not available]		020.09161111
Ache
[description not available]		08.581710
Pain
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.		08.581710
Mucositis
An INFLAMMATION of the MUCOSA with burning or tingling sensation. It is characterized by atrophy of the squamous EPITHELIUM, vascular damage, inflammatory infiltration, and ulceration. It usually occurs at the mucous lining of the MOUTH, the GASTROINTESTINAL TRACT or the airway due to chemical irritations, CHEMOTHERAPY, or radiation therapy (RADIOTHERAPY).		09.55215
Fibrosis, Radiation
[description not available]		018.1110790
Radiation Pneumonitis
Inflammation of the lung due to harmful effects of ionizing or non-ionizing radiation.		023.1110790
Cancer of Colon
[description not available]		010.26557
Colonic Neoplasms
Tumors or cancer of the COLON.		010.26557
Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Disorder characterized by symptoms of CATATONIA; HYPOVENTILATION; DYSKINESIAS; ENCEPHALITIS; and SEIZURES followed by a reduced CONSCIOUSNESS. It is often followed by a viral-like prodrome. Many cases are self-limiting and respond well to IMMUNOMODULATORY THERAPIES against the NMDA RECEPTORS antibodies.		02.610
Complication, Postoperative
[description not available]		012.24548
Bronchial Fistula
An abnormal passage or communication between a bronchus and another part of the body.		03.3160
Postoperative Complications
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.		012.24548
Carcinoma, Oat Cell
[description not available]		021.3410176
Carcinoma, Small Cell
An anaplastic, highly malignant, and usually bronchogenic carcinoma composed of small ovoid cells with scanty neoplasm. It is characterized by a dominant, deeply basophilic nucleus, and absent or indistinct nucleoli. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1286-7)		021.3410176
Anti-MuSK Myasthenia Gravis
[description not available]		02.4620
Acute Respiratory Distress Syndrome
[description not available]		05.131
Acute Hypercapnic Respiratory Failure
[description not available]		06.0252
Carcinoma, Thymic
[description not available]		011.873118
Cancer of the Thymus
[description not available]		013.124317
Myasthenia Gravis
A disorder of neuromuscular transmission characterized by fatigable weakness of cranial and skeletal muscles with elevated titers of ACETYLCHOLINE RECEPTORS or muscle-specific receptor tyrosine kinase (MuSK) autoantibodies. Clinical manifestations may include ocular muscle weakness (fluctuating, asymmetric, external ophthalmoplegia; diplopia; ptosis; and weakness of eye closure) and extraocular fatigable weakness of facial, bulbar, respiratory, and proximal limb muscles. The disease may remain limited to the ocular muscles (ocular myasthenia). THYMOMA is commonly associated with this condition.		07.4620
Respiratory Distress Syndrome
A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA.		05.131
Respiratory Insufficiency
Failure to adequately provide oxygen to cells of the body and to remove excess carbon dioxide from them. (Stedman, 25th ed)		06.0252
Thymoma
A neoplasm originating from thymic tissue, usually benign, and frequently encapsulated. Although it is occasionally invasive, metastases are extremely rare. It consists of any type of thymic epithelial cell as well as lymphocytes that are usually abundant. Malignant lymphomas that involve the thymus, e.g., lymphosarcoma, Hodgkin's disease (previously termed granulomatous thymoma), should not be regarded as thymoma. (From Stedman, 25th ed)		011.873118
Thymus Neoplasms
Tumors or cancer of the THYMUS GLAND.		013.124317
Allergic Reaction
[description not available]		04.9881
Hansen Disease
[description not available]		02.4110
Hypersensitivity
Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.		04.9881
Leprosy
A chronic granulomatous infection caused by MYCOBACTERIUM LEPRAE. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid.		07.4110
Chronic Kidney Diseases
[description not available]		010.74274
Renal Insufficiency, Chronic
Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)		010.74274
B-Cell Lymphoma
[description not available]		011.512716
Lymphoma, B-Cell
A group of heterogeneous lymphoid tumors generally expressing one or more B-cell antigens or representing malignant transformations of B-lymphocytes.		011.512716
Microsatellite Instability
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.		05.8561
Avian Diseases
[description not available]		02.5920
Papilloma, Squamous Cell
[description not available]		02.4920
Papilloma
A circumscribed benign epithelial tumor projecting from the surrounding surface; more precisely, a benign epithelial neoplasm consisting of villous or arborescent outgrowths of fibrovascular stroma covered by neoplastic cells. (Stedman, 25th ed)		02.4920
Granuloma, Hodgkin
[description not available]		012.335127
Hodgkin Disease
A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.		012.335127
Ocular Toxicity
[description not available]		07.610
Day Blindness
[description not available]		05.9691
Neuroendocrine Tumors
Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.		08.65180
Debility
[description not available]		03.1840
Cancer, Second Primary
[description not available]		014.39779
Blood Poisoning
[description not available]		07.69116
Sepsis
Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.		07.69116
Interstitial Cell Tumor
[description not available]		02.4110
Cytokine Release Syndrome
A severe immune reaction characterized by excessive release of CYTOKINES. Symptoms include DYSPNEA; FEVER; HEADACHE; HYPOTENSION; NAUSEA; RASH; TACHYCARDIA; HYPOXIA; HYPERFERRITINEMIA, and MULTIPLE ORGAN FAILURE. It is associated with viral infections, SEPSIS; AUTOIMMUNE DISEASES and a variety of factors used in IMMUNOTHERAPY.		02.4110
2019 Novel Coronavirus Disease
[description not available]		010.03129
Cancer of the Thyroid
[description not available]		010.55264
Thyroid Neoplasms
Tumors or cancer of the THYROID GLAND.		010.55264
Kidney Failure
A severe irreversible decline in the ability of kidneys to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism.		010.23244
Renal Insufficiency
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.		015.23244
Diabetes Mellitus, Adult-Onset
[description not available]		07.0691
Diabetes Mellitus, Type 2
A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.		07.0691
Anal Cancer
[description not available]		010.52150
Anus Neoplasms
Tumors or cancer of the ANAL CANAL.		05.52150
Cancer of Mediastinum
[description not available]		010.67409
Mediastinal Neoplasms
Tumors or cancer of the MEDIASTINUM.		010.67409
Colorectal Cancer
[description not available]		012.034014
Colorectal Neoplasms
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.		012.034014
Cancer of the Urethra
[description not available]		05.692
Urethral Neoplasms
Cancer or tumors of the URETHRA. Benign epithelial tumors of the urethra usually consist of squamous and transitional cells. Primary urethral carcinomas are rare and typically of squamous cells. Urethral carcinoma is the only urological malignancy that is more common in females than in males.		05.692
Androgen-Independent Prostatic Cancer
[description not available]		08.06273
Prostatic Neoplasms, Castration-Resistant
Tumors or cancer of the PROSTATE which can grow in the presence of low or residual amount of androgen hormones such as TESTOSTERONE.		08.06273
Alopecia Cicatrisata
[description not available]		011.154027
Alopecia
Absence of hair from areas where it is normally present.		011.154027
Deaf Mutism
[description not available]		07.02152
Deafness
A general term for the complete loss of the ability to hear from both ears.		07.02152
Neoplasm Seeding
The local implantation of tumor cells by contamination of instruments and surgical equipment during and after surgical resection, resulting in local growth of the cells and tumor formation.		07.65292
Thromboembolism, Venous
[description not available]		08.99194
Venous Thromboembolism
Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream.		013.99194
Anemia
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.		021.19280229
Pulsatile Tinnitus
[description not available]		08.4291
Tinnitus
A nonspecific symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, and other noises in the ear. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of COCHLEAR DISEASES; VESTIBULOCOCHLEAR NERVE DISEASES; INTRACRANIAL HYPERTENSION; CRANIOCEREBRAL TRAUMA; and other conditions.		08.4291
Anoxemia
[description not available]		06.45151
Hypoxia
Sub-optimal OXYGEN levels in the ambient air of living organisms.		06.45151
Soft Tissue Neoplasms
Neoplasms of whatever cell type or origin, occurring in the extraskeletal connective tissue framework of the body including the organs of locomotion and their various component structures, such as nerves, blood vessels, lymphatics, etc.		011.273414
Rodent Diseases
Diseases of rodents of the order RODENTIA. This term includes diseases of Sciuridae (squirrels), Geomyidae (gophers), Heteromyidae (pouched mice), Castoridae (beavers), Cricetidae (rats and mice), Muridae (Old World rats and mice), Erethizontidae (porcupines), and Caviidae (guinea pigs).		02.610
Amaurosis
[description not available]		06.4282
Blindness
The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of EYE DISEASES; OPTIC NERVE DISEASES; OPTIC CHIASM diseases; or BRAIN DISEASES affecting the VISUAL PATHWAYS or OCCIPITAL LOBE.		011.4282
Epithelial Neoplasms
[description not available]		021.91320135
Skin Diseases, Vascular
Skin diseases affecting or involving the cutaneous blood vessels and generally manifested as inflammation, swelling, erythema, or necrosis in the affected area.		02.4110
Thoracic Neoplasms
New abnormal growth of tissue in the THORAX.		07.87165
Hematuria
Presence of blood in the urine.		03.4270
Clostridioides difficile Infection
[description not available]		04.9421
Health Care Associated Infection
[description not available]		02.610
Clostridium Infections
Infections with bacteria of the genus CLOSTRIDIUM and closely related CLOSTRIDIOIDES species.		04.9421
Cross Infection
Any infection which a patient contracts in a health-care institution.		02.610
Carcinoma, Lobular
A type of BREAST CANCER where the abnormal malignant cells form in the lobules, or milk-producing glands, of the breast.		06.45114
Extra-Mammary Paget Disease
[description not available]		04.0650
Paget Disease, Extramammary
A rare cutaneous neoplasm that occurs in the elderly. It develops more frequently in women and predominantly involves apocrine gland-bearing areas, especially the vulva, scrotum, and perianal areas. The lesions develop as erythematous scaly patches that progress to crusted, pruritic, erythematous plaques. The clinical differential diagnosis includes squamous cell carcinoma in situ and superficial fungal infection. It is generally thought to be an adenocarcinoma of the epidermis, from which it extends into the contiguous epithelium of hair follicles and eccrine sweat ducts. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1478)		04.0650
Adenocarcinoma Of Kidney
[description not available]		012.25199
Carcinoma, Renal Cell
A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.		012.25199
Carcinoma, Medullary
A carcinoma composed mainly of epithelial elements with little or no stroma. Medullary carcinomas of the breast constitute 5%-7% of all mammary carcinomas; medullary carcinomas of the thyroid comprise 3%-10% of all thyroid malignancies. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1141; Segen, Dictionary of Modern Medicine, 1992)		02.8530
Experimental Lung Inflammation
Inflammation of any part, segment or lobe, of the lung parenchyma.		08.9156
Pneumonia
Infection of the lung often accompanied by inflammation.		08.9156
Allergic Encephalomyelitis
[description not available]		02.610
MS (Multiple Sclerosis)
[description not available]		02.610
Multiple Sclerosis
An autoimmune disorder mainly affecting young adults and characterized by destruction of myelin in the central nervous system. Pathologic findings include multiple sharply demarcated areas of demyelination throughout the white matter of the central nervous system. Clinical manifestations include visual loss, extra-ocular movement disorders, paresthesias, loss of sensation, weakness, dysarthria, spasticity, ataxia, and bladder dysfunction. The usual pattern is one of recurrent attacks followed by partial recovery (see MULTIPLE SCLEROSIS, RELAPSING-REMITTING), but acute fulminating and chronic progressive forms (see MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE) also occur. (Adams et al., Principles of Neurology, 6th ed, p903)		02.610
Gestational Trophoblastic Neoplasia
Gestational Trophoblastic diseases that are malignant. It does not include HYDATIDIFORM MOLE. However, there is a minority of authors that consider the term gestational trophoblastic neoplasia synonymous with gestational trophoblastic disease.		04.3260
Gestational Trophoblastic Disease
A group of diseases arising from pregnancy that are commonly associated with hyperplasia of trophoblasts (TROPHOBLAST) and markedly elevated human CHORIONIC GONADOTROPIN. They include HYDATIDIFORM MOLE, invasive mole (HYDATIDIFORM MOLE, INVASIVE), placental-site trophoblastic tumor (TROPHOBLASTIC TUMOR, PLACENTAL SITE), and CHORIOCARCINOMA. These neoplasms have varying propensities for invasion and spread.		04.3260
Cramp
[description not available]		02.610
Idiopathic Inflammatory Myopathies
[description not available]		03.7230
Muscle Cramp
A sustained and usually painful contraction of muscle fibers. This may occur as an isolated phenomenon or as a manifestation of an underlying disease process (e.g., UREMIA; HYPOTHYROIDISM; MOTOR NEURON DISEASE; etc.). (From Adams et al., Principles of Neurology, 6th ed, p1398)		02.610
Myositis
Inflammation of a muscle or muscle tissue.		08.7230
Adenocystic Carcinoma
[description not available]		07.62121
Carcinoma, Adenoid Cystic
Carcinoma characterized by bands or cylinders of hyalinized or mucinous stroma separating or surrounded by nests or cords of small epithelial cells. When the cylinders occur within masses of epithelial cells, they give the tissue a perforated, sievelike, or cribriform appearance. Such tumors occur in the mammary glands, the mucous glands of the upper and lower respiratory tract, and the salivary glands. They are malignant but slow-growing, and tend to spread locally via the nerves. (Dorland, 27th ed)		07.62121
Idiopathic Interstitial Pneumonia
[description not available]		06.8764
Dysmyelopoietic Syndromes
[description not available]		06.51101
Myelodysplastic Syndromes
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.		06.51101
Dysgeusia
A condition characterized by alterations of the sense of taste which may range from mild to severe, including gross distortions of taste quality.		04.231
Deficiency, Folic Acid
[description not available]		02.610
Deficiency, Vitamin B 12
[description not available]		02.610
Folic Acid Deficiency
A nutritional condition produced by a deficiency of FOLIC ACID in the diet. Many plant and animal tissues contain folic acid, abundant in green leafy vegetables, yeast, liver, and mushrooms but destroyed by long-term cooking. Alcohol interferes with its intermediate metabolism and absorption. Folic acid deficiency may develop in long-term anticonvulsant therapy or with use of oral contraceptives. This deficiency causes anemia, macrocytic anemia, and megaloblastic anemia. It is indistinguishable from vitamin B 12 deficiency in peripheral blood and bone marrow findings, but the neurologic lesions seen in B 12 deficiency do not occur. (Merck Manual, 16th ed)		02.610
Vitamin B 12 Deficiency
A nutritional condition produced by a deficiency of VITAMIN B 12 in the diet, characterized by megaloblastic anemia. Since vitamin B 12 is not present in plants, humans have obtained their supply from animal products, from multivitamin supplements in the form of pills, and as additives to food preparations. A wide variety of neuropsychiatric abnormalities is also seen in vitamin B 12 deficiency and appears to be due to an undefined defect involving myelin synthesis. (From Cecil Textbook of Medicine, 19th ed, p848)		02.610
Lymph Node Metastasis
[description not available]		021.3328115
Febrile Neutropenia
Fever accompanied by a significant reduction in the number of NEUTROPHILS.		08.6394
Cancer of the Ureter
[description not available]		09.14174
Ureteral Neoplasms
Cancer or tumors of the URETER which may cause obstruction leading to hydroureter, HYDRONEPHROSIS, and PYELONEPHRITIS. HEMATURIA is a common symptom.		09.14174
Adrenocortical Carcinoma
A malignant neoplasm of the ADRENAL CORTEX. Adrenocortical carcinomas are unencapsulated anaplastic (ANAPLASIA) masses sometimes exceeding 20 cm or 200 g. They are more likely to be functional than nonfunctional, and produce ADRENAL CORTEX HORMONES that may result in hypercortisolism (CUSHING SYNDROME); HYPERALDOSTERONISM; and/or VIRILISM.		08.2750
Adrenal Cortex Cancer
[description not available]		03.3160
Adrenal Cortex Neoplasms
Tumors or cancers of the ADRENAL CORTEX.		03.3160
Cancer of the Tongue
[description not available]		014.09323
Tongue Neoplasms
Tumors or cancer of the TONGUE.		09.09323
Fibroid
[description not available]		02.6320
Giant Cell Tumors
Tumors of bone tissue or synovial or other soft tissue characterized by the presence of giant cells. The most common are giant cell tumor of tendon sheath and GIANT CELL TUMOR OF BONE.		02.610
Leiomyoma
A benign tumor derived from smooth muscle tissue, also known as a fibroid tumor. They rarely occur outside of the UTERUS and the GASTROINTESTINAL TRACT but can occur in the SKIN and SUBCUTANEOUS TISSUE, probably arising from the smooth muscle of small blood vessels in these tissues.		02.6320
Cardiac Toxicity
[description not available]		05.0721
Cardiotoxicity
Damage to the HEART or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION.		05.0721
Bilirubinemia
[description not available]		02.4820
Icterus
[description not available]		02.610
Liver Dysfunction
[description not available]		03.6930
Jaundice
A clinical manifestation of HYPERBILIRUBINEMIA, characterized by the yellowish staining of the SKIN; MUCOUS MEMBRANE; and SCLERA. Clinical jaundice usually is a sign of LIVER dysfunction.		07.610
Liver Diseases
Pathological processes of the LIVER.		03.6930
Invasiveness, Neoplasm
[description not available]		019.0517542
Cancer of Gallbladder
[description not available]		06.64102
Gallbladder Neoplasms
Tumors or cancer of the gallbladder.		06.64102
Encephalitis, JC Polyomavirus
[description not available]		02.7530
Leukoencephalopathy, Progressive Multifocal
An opportunistic viral infection of the central nervous system associated with conditions that impair cell-mediated immunity (e.g., ACQUIRED IMMUNODEFICIENCY SYNDROME and other IMMUNOLOGIC DEFICIENCY SYNDROMES; HEMATOLOGIC NEOPLASMS; IMMUNOSUPPRESSION; and COLLAGEN DISEASES). The causative organism is JC Polyomavirus (JC VIRUS) which primarily affects oligodendrocytes, resulting in multiple areas of demyelination. Clinical manifestations include DEMENTIA; ATAXIA; visual disturbances; and other focal neurologic deficits, generally progressing to a vegetative state within 6 months. (From Joynt, Clinical Neurology, 1996, Ch26, pp36-7)		02.7530
Leukoencephalopathy Syndrome, Posterior
[description not available]		03.1950
Mixed Tumor, Mullerian
A tumor, basically a carcinoma with a single sarcoma such as leiomyosarcoma or angiosarcoma or multiple sarcomas of uterine origin. The role of estrogen has been postulated as a possible etiological factor in this tumor. (Holland et al., Cancer Medicine, 3d ed, p1703)		09.36185
Carcinoma, Papillary
A malignant neoplasm characterized by the formation of numerous, irregular, finger-like projections of fibrous stroma that is covered with a surface layer of neoplastic epithelial cells. (Stedman, 25th ed)		010.01417
Preterm Birth
[description not available]		03.9540
Stillbirth
The event that a FETUS is born dead or stillborn.		02.2110
Neonatal Death
The death of a live-born INFANT less than 28 days of age.		02.2110
Abnormalities, Congenital
[description not available]		02.2110
Infantile Respiratory Distress Syndrome
[description not available]		02.2110
Infant, Small for Gestational Age
An infant having a birth weight lower than expected for its gestational age.		02.2110
Respiratory Distress Syndrome, Newborn
A condition of the newborn marked by DYSPNEA with CYANOSIS, heralded by such prodromal signs as dilatation of the alae nasi, expiratory grunt, and retraction of the suprasternal notch or costal margins, mostly frequently occurring in premature infants, children of diabetic mothers, and infants delivered by cesarean section, and sometimes with no apparent predisposing cause.		02.2110
Premature Birth
CHILDBIRTH before 37 weeks of PREGNANCY (259 days from the first day of the mother's last menstrual period, or 245 days after FERTILIZATION).		03.9540
Cancer of Intestines
[description not available]		04.9380
Adenocarcinoma, Papillary
An adenocarcinoma containing finger-like processes of vascular connective tissue covered by neoplastic epithelium, projecting into cysts or the cavity of glands or follicles. It occurs most frequently in the ovary and thyroid gland. (Stedman, 25th ed)		07.65213
Intestinal Perforation
Opening or penetration through the wall of the INTESTINES.		08.94152
Intestinal Neoplasms
Tumors or cancer of the INTESTINES.		04.9380
Anemia, Hemolytic, Acquired
[description not available]		03.5280
Anemia, Hemolytic
A condition of inadequate circulating red blood cells (ANEMIA) or insufficient HEMOGLOBIN due to premature destruction of red blood cells (ERYTHROCYTES).		03.5280
Sarcopenia
Progressive decline in muscle mass due to aging which results in decreased functional capacity of muscles.		09.2431
Brain Disorders
[description not available]		04.3841
Brain Diseases
Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.		04.3841
Yolk Sac Tumor
[description not available]		05.0590
Endodermal Sinus Tumor
An unusual and aggressive tumor of germ-cell origin that reproduces the extraembryonic structures of the early embryo. It is the most common malignant germ cell tumor found in children. It is characterized by a labyrinthine glandular pattern of flat epithelial cells and rounded papillary processes with a central capillary (Schiller-Duval body). The tumor is rarely bilateral. Before the use of combination chemotherapy, the tumor was almost invariably fatal. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1189)		05.0590
Cell Transformation, Neoplastic
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.		07.57172
Response Evaluation Criteria in Solid Tumors
An internationally recognized set of published rules used for evaluation of cancer treatment that define when tumors found in cancer patients improve, worsen, or remain stable during treatment. These criteria are based specifically on the response of the tumor(s) to treatment, and not on the overall health status of the patient resulting from treatment.		016.6410196
Kahler Disease
[description not available]		08.2114
Multiple Myeloma
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.		08.2114
Mesothelioma
A tumor derived from mesothelial tissue (peritoneum, pleura, pericardium). It appears as broad sheets of cells, with some regions containing spindle-shaped, sarcoma-like cells and other regions showing adenomatous patterns. Pleural mesotheliomas have been linked to exposure to asbestos. (Dorland, 27th ed)		017.212139
Bacterial Infections, Gram-Positive
[description not available]		02.2510
Hypogammaglobulinemia
[description not available]		02.2510
Agammaglobulinemia
An immunologic deficiency state characterized by an extremely low level of generally all classes of gamma-globulin in the blood.		02.2510
Gram-Positive Bacterial Infections
Infections caused by bacteria that retain the crystal violet stain (positive) when treated by the gram-staining method.		02.2510
Cognitive Decline
[description not available]		02.5820
Cognitive Dysfunction
Diminished or impaired mental and/or intellectual function.		02.5820
Esophageal Fistula
Abnormal passage communicating with the ESOPHAGUS. The most common type is TRACHEOESOPHAGEAL FISTULA between the esophagus and the TRACHEA.		04.3441
Esophagitis
INFLAMMATION, acute or chronic, of the ESOPHAGUS caused by BACTERIA, chemicals, or TRAUMA.		018.424833
Complications, Pregnancy
[description not available]		03.4620
Extravasation of Contrast Media
[description not available]		03.1450
Rhabdoid Tumor
A rare but highly lethal childhood tumor found almost exclusively in infants. Histopathologically, it resembles RHABDOMYOSARCOMA but the tumor cells are not of myogenic origin. Although it arises primarily in the kidney, it may be found in other parts of the body. The rhabdoid cytomorphology is believed to be the expression of a very primitive malignant cell. (From Holland et al., Cancer Medicine, 3d ed, p2210)		05.71102
Cancer of Nose
[description not available]		07.83153
Cancer of the Vulva
[description not available]		06.23121
Vulvar Neoplasms
Tumors or cancer of the VULVA.		06.23121
Choroid Neoplasms
Tumors of the choroid; most common intraocular tumors are malignant melanomas of the choroid. These usually occur after puberty and increase in incidence with advancing age. Most malignant melanomas of the uveal tract develop from benign melanomas (nevi).		03.2960
Long Sleeper Syndrome
[description not available]		02.2510
Sleep Wake Disorders
Abnormal sleep-wake schedule or pattern associated with the CIRCADIAN RHYTHM which affect the length, timing, and/or rigidity of the sleep-wake cycle relative to the day-night cycle.		02.2510
Interstitial Nephritis
[description not available]		07.5120
Acute Disease
Disease having a short and relatively severe course.		013.24617
Nephritis, Interstitial
Inflammation of the interstitial tissue of the kidney. This term is generally used for primary inflammation of KIDNEY TUBULES and/or surrounding interstitium. For primary inflammation of glomerular interstitium, see GLOMERULONEPHRITIS. Infiltration of the inflammatory cells into the interstitial compartment results in EDEMA, increased spaces between the tubules, and tubular renal dysfunction.		02.5120
Menstruation, Painful
[description not available]		02.2510
Endometrioma
An enlarged area of ENDOMETRIOSIS that resembles a tumor. It is usually found in the OVARY. When it is filled with old blood, it is known as a chocolate cyst.		05.22110
Sterility, Female
[description not available]		03.0240
Ovarian Diseases
Pathological processes of the OVARY.		02.730
Pelvic Pain
Pain in the pelvic region of genital and non-genital origin.		03.4720
Dysmenorrhea
Painful menstruation.		02.2510
Endometriosis
A condition in which functional endometrial tissue is present outside the UTERUS. It is often confined to the PELVIS involving the OVARY, the ligaments, cul-de-sac, and the uterovesical peritoneum.		05.22110
Infertility, Female
Diminished or absent ability of a female to achieve conception.		03.0240
Adenocarcinoma, Clear Cell
An adenocarcinoma characterized by the presence of varying combinations of clear and hobnail-shaped tumor cells. There are three predominant patterns described as tubulocystic, solid, and papillary. These tumors, usually located in the female reproductive organs, have been seen more frequently in young women since 1970 as a result of the association with intrauterine exposure to diethylstilbestrol. (From Holland et al., Cancer Medicine, 3d ed)		014.739918
Adult Optic Nerve Glioma
[description not available]		06.39141
Optic Nerve Glioma
Glial cell derived tumors arising from the optic nerve, usually presenting in childhood.		06.39141
Retinal Diseases
Diseases involving the RETINA.		04.09140
Acute Generalised Exanthematous Pustulosis
[description not available]		02.2510
Experimental Neoplasms
[description not available]		06.73400
Orphan Diseases
Rare diseases that have not been well studied.		03.2450
Carcinoma, Ductal, Breast
An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.		013.044521
Hallucination of Body Sensation
[description not available]		02.2510
Nerve Pain
[description not available]		05.8142
Acid Aspiration Syndrome
[description not available]		02.4920
Autoimmune Diseases of the Nervous System
Disorders caused by cellular or humoral immune responses primarily directed towards nervous system autoantigens. The immune response may be directed towards specific tissue components (e.g., myelin) and may be limited to the central nervous system (e.g., MULTIPLE SCLEROSIS) or the peripheral nervous system (e.g., GUILLAIN-BARRE SYNDROME).		02.2510
Autonomic Dysfunction, Paraneoplastic
[description not available]		04.2860
Merkel Cell Cancer
[description not available]		07.26225
Hallucinations
Subjectively experienced sensations in the absence of an appropriate stimulus, but which are regarded by the individual as real. They may be of organic origin or associated with MENTAL DISORDERS.		02.2510
Neuralgia
Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.		05.8142
Pneumonia, Aspiration
A type of lung inflammation resulting from the aspiration of food, liquid, or gastric contents into the upper RESPIRATORY TRACT.		02.4920
Carcinoma, Merkel Cell
A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245)		07.26225
Blood Clot
[description not available]		06.4182
Ascites
Accumulation or retention of free fluid within the peritoneal cavity.		013.01303
Thrombosis
Formation and development of a thrombus or blood clot in the blood vessel.		011.4182
Neoplasms, Pleural
[description not available]		016.058630
Intraocular Pressure
The pressure of the fluids in the eye.		02.6320
Cafe-au-Lait Spots with Pulmonic Stenosis
[description not available]		07.77132
Neoplasms, Nerve Sheath
[description not available]		02.9940
Neurofibromatosis 1
An autosomal dominant inherited disorder (with a high frequency of spontaneous mutations) that features developmental changes in the nervous system, muscles, bones, and skin, most notably in tissue derived from the embryonic NEURAL CREST. Multiple hyperpigmented skin lesions and subcutaneous tumors are the hallmark of this disease. Peripheral and central nervous system neoplasms occur frequently, especially OPTIC NERVE GLIOMA and NEUROFIBROSARCOMA. NF1 is caused by mutations which inactivate the NF1 gene (GENES, NEUROFIBROMATOSIS 1) on chromosome 17q. The incidence of learning disabilities is also elevated in this condition. (From Adams et al., Principles of Neurology, 6th ed, pp1014-18) There is overlap of clinical features with NOONAN SYNDROME in a syndrome called neurofibromatosis-Noonan syndrome. Both the PTPN11 and NF1 gene products are involved in the SIGNAL TRANSDUCTION pathway of Ras (RAS PROTEINS).		07.77132
Nerve Sheath Neoplasms
Neoplasms which arise from nerve sheaths formed by SCHWANN CELLS in the PERIPHERAL NERVOUS SYSTEM or by OLIGODENDROCYTES in the CENTRAL NERVOUS SYSTEM. Malignant peripheral nerve sheath tumors, NEUROFIBROMA, and NEURILEMMOMA are relatively common tumors in this category.		02.9940
Anasarca
[description not available]		08.09154
Eye Disorders
[description not available]		04.551
Edema
Abnormal fluid accumulation in TISSUES or body cavities. Most cases of edema are present under the SKIN in SUBCUTANEOUS TISSUE.		013.09154
Eye Diseases
Diseases affecting the eye.		04.551
Acantholysis
Separation of the prickle cells of the stratum spinosum of the epidermis, resulting in atrophy of the prickle cell layer. It is seen in diseases such as pemphigus vulgaris (see PEMPHIGUS) and DARIER DISEASE.		02.2510
Xeroderma
[description not available]		02.5220
Ichthyosis
Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome.		02.5220
Conjugate Nystagmus
[description not available]		02.8730
Colon Cancer, Familial Nonpolyposis
[description not available]		02.2510
Colorectal Neoplasms, Hereditary Nonpolyposis
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.		02.2510
Cancer of Digestive System
[description not available]		05.0852
Genito-urinary Cancer
[description not available]		014.8132
Digestive System Neoplasms
Tumors or cancer of the DIGESTIVE SYSTEM.		05.0852
Urogenital Neoplasms
Tumors or cancer of the UROGENITAL SYSTEM in either the male or the female.		09.8132
Birth Weight
The mass or quantity of heaviness of an individual at BIRTH. It is expressed by units of pounds or kilograms.		04.4311
Hibernation, Myocardial
[description not available]		04.4311
Tuberculosis, Drug-Resistant
[description not available]		04.4311
Infections, Coronavirus
[description not available]		09.85109
Chronic Hepatitis B
[description not available]		05.5231
Anterior Cerebral Circulation Infarction
[description not available]		04.4311
Apoplexy
[description not available]		06.8751
Airflow Obstruction, Chronic
[description not available]		04.821
Ductal Carcinoma
[description not available]		05.0731
Gastrointestinal Stromal Neoplasm
[description not available]		04.8321
Complications of Diabetes Mellitus
[description not available]		05.3422
Overweight
A status with BODY WEIGHT that is above certain standards. In the scale of BODY MASS INDEX, overweight is defined as having a BMI of 25.0-29.9 kg/m2. Overweight may or may not be due to increases in body fat (ADIPOSE TISSUE), hence overweight does not equal over fat.		07.3782
Atherogenesis
[description not available]		07.7254
Bone Fractures
[description not available]		05.6332
Primary Graft Dysfunction
A form of ischemia-reperfusion injury occurring in the early period following transplantation. Significant pathophysiological changes in MITOCHONDRIA are the main cause of the dysfunction. It is most often seen in the transplanted lung, liver, or kidney and can lead to GRAFT REJECTION.		04.4311
Lung Injury, Acute
[description not available]		04.7921
Airway Remodeling
The structural changes in the number, mass, size and/or composition of the airway tissues.		04.4311
Atheroma
[description not available]		04.4311
Lower Urinary Tract Symptom
[description not available]		04.4311
Adolescent Obesity
[description not available]		04.4311
Allergic Rhinitis
[description not available]		04.4311
Thyroid Cancer, Anaplastic
[description not available]		05.3341
Encephalopathy, Traumatic
[description not available]		04.4311
Familial Nonmedullary Thyroid Cancer
[description not available]		04.821
Acute Confusional Senile Dementia
[description not available]		07.5544
Rheumatoid Arthritis
[description not available]		04.4311
Bone Loss, Osteoclastic
[description not available]		04.7421
Carcinoma, Ehrlich Tumor
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.		05.4351
Alloxan Diabetes
[description not available]		05.1231
Autoimmune Diabetes
[description not available]		04.4311
Cutis Elastica
[description not available]		04.4311
E coli Infections
[description not available]		04.7721
Exanthem
[description not available]		010.39139
Cardiac Failure
[description not available]		017.732217
Extravascular Hemolysis
[description not available]		05.5651
Bleeding
[description not available]		011.03187
Hepatitis B Virus Infection
[description not available]		08.0164
Fasting Hypoglycemia
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.		05.0731
Hypermobility, Joint
[description not available]		04.4311
Chronic Kidney Failure
[description not available]		08.47322
Cirrhosis, Liver
[description not available]		04.4311
B16 Melanoma
[description not available]		06.29131
Muscle Disorders
[description not available]		06.2672
Morbid Obesity
[description not available]		04.4311
Age-Related Osteoporosis
[description not available]		07.5544
Prediabetes
[description not available]		04.4311
Cancer of Salivary Gland
[description not available]		07.1102
Hemorrhagic Shock
[description not available]		04.4311
Pulmonary Consumption
[description not available]		05.0731
Deficiency, Vitamin D
[description not available]		05.6532
Injuries
Used with anatomic headings, animals, and sports for wounds and injuries. Excludes cell damage, for which pathology is used.		04.4311
Injury, Ischemia-Reperfusion
[description not available]		04.4311
Bone Loss, Perimenopausal
[description not available]		05.2721
Bacterial Infections, Gram-Negative
[description not available]		07.5544
Carcinoma, Ductal, Pancreatic
[description not available]		04.4311
Hangman Fracture
[description not available]		05.2721
Eye Infections, Fungal
Infection by a variety of fungi, usually through four possible mechanisms: superficial infection producing conjunctivitis, keratitis, or lacrimal obstruction; extension of infection from neighboring structures - skin, paranasal sinuses, nasopharynx; direct introduction during surgery or accidental penetrating trauma; or via the blood or lymphatic routes in patients with underlying mycoses.		04.4311
Cell Transformation, Viral
An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus.		05.0731
Delayed Effects, Prenatal Exposure
[description not available]		04.7821
Brain Injuries, Traumatic
A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain.		04.4311
Aging
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.		08.83146
Albuminuria
The presence of albumin in the urine, an indicator of KIDNEY DISEASES.		05.7942
Alzheimer Disease
A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)		07.5544
Arthritis, Rheumatoid
A chronic systemic disease, primarily of the joints, marked by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Etiology is unknown, but autoimmune mechanisms have been implicated.		04.4311
Cardiovascular Diseases
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.		09.44165
Colitis
Inflammation of the COLON section of the large intestine (INTESTINE, LARGE), usually with symptoms such as DIARRHEA (often with blood and mucus), ABDOMINAL PAIN, and FEVER.		05.0131
Connective Tissue Diseases
A heterogeneous group of disorders, some hereditary, others acquired, characterized by abnormal structure or function of one or more of the elements of connective tissue, i.e., collagen, elastin, or the mucopolysaccharides.		04.4311
Diabetes Mellitus, Type 1
A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.		04.4311
Ehlers-Danlos Syndrome
A heterogeneous group of autosomally inherited COLLAGEN DISEASES caused by defects in the synthesis or structure of FIBRILLAR COLLAGEN. There are numerous subtypes: classical, hypermobility, vascular, and others. Common clinical features include hyperextensible skin and joints, skin fragility and reduced wound healing capability.		04.4311
Escherichia coli Infections
Infections with bacteria of the species ESCHERICHIA COLI.		04.7721
Exanthema
Diseases in which skin eruptions or rashes are a prominent manifestation. Classically, six such diseases were described with similar rashes; they were numbered in the order in which they were reported. Only the fourth (Duke's disease), fifth (ERYTHEMA INFECTIOSUM), and sixth (EXANTHEMA SUBITUM) numeric designations survive as occasional synonyms in current terminology.		010.39139
Heart Failure
A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.		012.732217
Hemolysis
The destruction of ERYTHROCYTES by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity.		05.5651
Hemorrhage
Bleeding or escape of blood from a vessel.		011.03187
Hepatitis B
INFLAMMATION of the LIVER in humans caused by a member of the ORTHOHEPADNAVIRUS genus, HEPATITIS B VIRUS. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.		08.0164
Hypoglycemia
A syndrome of abnormally low BLOOD GLUCOSE level. Clinical hypoglycemia has diverse etiologies. Severe hypoglycemia eventually lead to glucose deprivation of the CENTRAL NERVOUS SYSTEM resulting in HUNGER; SWEATING; PARESTHESIA; impaired mental function; SEIZURES; COMA; and even DEATH.		05.0731
Kidney Failure, Chronic
The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.		08.47322
Liver Cirrhosis
Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules.		04.4311
Muscular Diseases
Acquired, familial, and congenital disorders of SKELETAL MUSCLE and SMOOTH MUSCLE.		06.2672
Necrosis
The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.		09.33293
Obesity
A status with BODY WEIGHT that is grossly above the recommended standards, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).		017.733213
Obesity, Morbid
The condition of weighing two, three, or more times the ideal weight, so called because it is associated with many serious and life-threatening disorders. In the BODY MASS INDEX, morbid obesity is defined as having a BMI greater than 40.0 kg/m2.		04.4311
Osteoporosis
Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.		07.5544
Pneumonia, Viral
Inflammation of the lung parenchyma that is caused by a viral infection.		09.85109
Prediabetic State
The time period before the development of symptomatic diabetes. For example, certain risk factors can be observed in subjects who subsequently develop INSULIN RESISTANCE as in type 2 diabetes (DIABETES MELLITUS, TYPE 2).		04.4311
Salivary Gland Neoplasms
Tumors or cancer of the SALIVARY GLANDS.		07.1102
Tuberculosis, Pulmonary
MYCOBACTERIUM infections of the lung.		05.0731
Uveitis
Inflammation of part or all of the uvea, the middle (vascular) tunic of the eye, and commonly involving the other tunics (sclera and cornea, and the retina). (Dorland, 27th ed)		04.7821
Vitamin D Deficiency
A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)		05.6532
Wounds and Injuries
Damage inflicted on the body as the direct or indirect result of an external force, with or without disruption of structural continuity.		04.4311
Reperfusion Injury
Adverse functional, metabolic, or structural changes in tissues that result from the restoration of blood flow to the tissue (REPERFUSION) following ISCHEMIA.		04.4311
Osteoporosis, Postmenopausal
Metabolic disorder associated with fractures of the femoral neck, vertebrae, and distal forearm. It occurs commonly in women within 15-20 years after menopause, and is caused by factors associated with menopause including estrogen deficiency.		05.2721
Spinal Fractures
Broken bones in the vertebral column.		05.2721
Gram-Negative Bacterial Infections
Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.		07.5544
Tuberculosis, Multidrug-Resistant
Tuberculosis resistant to chemotherapy with two or more ANTITUBERCULAR AGENTS, including at least ISONIAZID and RIFAMPICIN. The problem of resistance is particularly troublesome in tuberculous OPPORTUNISTIC INFECTIONS associated with HIV INFECTIONS. It requires the use of second line drugs which are more toxic than the first line regimens. TB with isolates that have developed further resistance to at least three of the six classes of second line drugs is defined as EXTENSIVELY DRUG-RESISTANT TUBERCULOSIS.		04.4311
Coronavirus Infections
Virus diseases caused by the CORONAVIRUS genus. Some specifics include transmissible enteritis of turkeys (ENTERITIS, TRANSMISSIBLE, OF TURKEYS); FELINE INFECTIOUS PERITONITIS; and transmissible gastroenteritis of swine (GASTROENTERITIS, TRANSMISSIBLE, OF SWINE).		09.85109
Hepatitis B, Chronic
INFLAMMATION of the LIVER in humans caused by HEPATITIS B VIRUS lasting six months or more. It is primarily transmitted by parenteral exposure, such as transfusion of contaminated blood or blood products, but can also be transmitted via sexual or intimate personal contact.		05.5231
Brain Infarction
Tissue NECROSIS in any area of the brain, including the CEREBRAL HEMISPHERES, the CEREBELLUM, and the BRAIN STEM. Brain infarction is the result of a cascade of events initiated by inadequate blood flow through the brain that is followed by HYPOXIA and HYPOGLYCEMIA in brain tissue. Damage may be temporary, permanent, selective or pan-necrosis.		04.4311
Stroke
A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to BRAIN ISCHEMIA or INTRACRANIAL HEMORRHAGES. Stroke is classified by the type of tissue NECROSIS, such as the anatomic location, vasculature involved, etiology, age of the affected individual, and hemorrhagic vs. non-hemorrhagic nature. (From Adams et al., Principles of Neurology, 6th ed, pp777-810)		06.8751
Carcinoma, Pancreatic Ductal
Carcinoma that arises from the PANCREATIC DUCTS. It accounts for the majority of cancers derived from the PANCREAS.		04.4311
Pulmonary Disease, Chronic Obstructive
A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.		04.821
Carcinoma, Ductal
Malignant neoplasms involving the ductal systems of any of a number of organs, such as the MAMMARY GLANDS, the PANCREAS, the PROSTATE, or the LACRIMAL GLAND.		05.0731
Gastrointestinal Stromal Tumors
All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).		04.8321
Atherosclerosis
A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.		07.7254
Fractures, Bone
Breaks in bones.		05.6332
Acute Lung Injury
A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).		04.7921
Rhinitis, Allergic
An inflammation of the NASAL MUCOSA triggered by ALLERGENS.		04.4311
Thyroid Carcinoma, Anaplastic
An aggressive THYROID GLAND malignancy which generally occurs in IODINE-deficient areas in people with previous thyroid pathology such as GOITER. It is associated with CELL DEDIFFERENTIATION of THYROID CARCINOMA (e.g., FOLLICULAR THYROID CARCINOMA; PAPILLARY THYROID CANCER). Typical initial presentation is a rapidly growing neck mass which upon metastasis is associated with DYSPHAGIA; NECK PAIN; bone pain; DYSPNEA; and NEUROLOGIC DEFICITS.		05.3341
Neoplasms, Squamous Cell
Neoplasms of the SQUAMOUS EPITHELIAL CELLS. The concept does not refer to neoplasms located in tissue composed of squamous elements.		011.412318
Deep Vein Thrombosis
[description not available]		03.8821
Phlegmasia Alba Dolens
Inflammation that is characterized by swollen, pale, and painful limb. It is usually caused by DEEP VEIN THROMBOSIS in a FEMORAL VEIN, following PARTURITION or an illness. This condition is also called milk leg or white leg.		03.4120
Thrombophlebitis
Inflammation of a vein associated with a blood clot (THROMBUS).		03.4120
Venous Thrombosis
The formation or presence of a blood clot (THROMBUS) within a vein.		03.8821
Dysembryoma
[description not available]		08.1343
Teratoma
A true neoplasm composed of a number of different types of tissue, none of which is native to the area in which it occurs. It is composed of tissues that are derived from three germinal layers, the endoderm, mesoderm, and ectoderm. They are classified histologically as mature (benign) or immature (malignant). (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1642)		08.1343
Pleural Effusion, Malignant
Presence of fluid in the PLEURAL CAVITY as a complication of malignant disease. Malignant pleural effusions often contain actual malignant cells.		010.85377
Granulocytic Leukemia, Chronic
[description not available]		09.31169
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.		09.31169
Sensitivity and Specificity
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)		012.04667
Acquired Encephalocele
[description not available]		02.2510
Cranial Sinus Thrombosis
[description not available]		02.2510
Cerebrospinal Fluid Rhinorrhea
Discharge of cerebrospinal fluid through the nose. Common etiologies include trauma, neoplasms, and prior surgery, although the condition may occur spontaneously. (Otolaryngol Head Neck Surg 1997 Apr;116(4):442-9)		02.2510
Adrenal Cancer
[description not available]		09.31214
FMR1-Related Primary Ovarian Insufficiency
[description not available]		02.2510
Primary Ovarian Insufficiency
Cessation of ovarian function after MENARCHE but before the age of 40, without or with OVARIAN FOLLICLE depletion. It is characterized by the presence of OLIGOMENORRHEA or AMENORRHEA, elevated GONADOTROPINS, and low ESTRADIOL levels. It is a state of female HYPERGONADOTROPIC HYPOGONADISM. Etiologies include genetic defects, autoimmune processes, chemotherapy, radiation, and infections. The most commonly known genetic cause is the expansion of a CGG repeat to 55 to 199 copies in the 5' untranslated region in the X-linked FMR1 gene.		02.2510
Rupture, Spontaneous
Tear or break of an organ, vessel or other soft part of the body, occurring in the absence of external force.		04.3941
Urinary Incontinence, Stress
Involuntary discharge of URINE as a result of physical activities that increase abdominal pressure on the URINARY BLADDER without detrusor contraction or overdistended bladder. The subtypes are classified by the degree of leakage, descent and opening of the bladder neck and URETHRA without bladder contraction, and sphincter deficiency.		02.2510
Acute Liver Injury, Drug-Induced
[description not available]		07.73145
Hepatitis
INFLAMMATION of the LIVER.		07.5520
Chemical and Drug Induced Liver Injury
A spectrum of clinical liver diseases ranging from mild biochemical abnormalities to ACUTE LIVER FAILURE, caused by drugs, drug metabolites, herbal and dietary supplements and chemicals from the environment.		07.73145
Leukocytopenia
[description not available]		01716488
Aphthae
[description not available]		02.3110
Asialia
[description not available]		09.69168
Dermatitis
Any inflammation of the skin.		05.4351
Leukopenia
A decrease in the number of LEUKOCYTES in a blood sample below the normal range (LEUKOCYTE COUNT less than 4000).		01716488
Stomatitis, Aphthous
A recurrent disease of the oral mucosa of unknown etiology. It is characterized by small white ulcerative lesions, single or multiple, round or oval. Two to eight crops of lesions occur per year, lasting for 7 to 14 days and then heal without scarring. (From Jablonski's Dictionary of Dentistry, 1992, p742)		02.3110
Xerostomia
Decreased salivary flow.		09.69168
Benign Optic Nerve Neoplasm
[description not available]		07.11172
Carcinoma, Colloid
[description not available]		011.614712
Adenocarcinoma, Mucinous
An adenocarcinoma producing mucin in significant amounts. (From Dorland, 27th ed)		011.614712
Clerambault Syndrome
[description not available]		03.520
Encephalopathy, Toxic
[description not available]		010.16193
Atopic Hypersensitivity
[description not available]		02.830
Cholecystoduodenal Fistula
[description not available]		05.131
Vaginal Fistula
An abnormal anatomical passage that connects the VAGINA to other organs, such as the bladder (VESICOVAGINAL FISTULA) or the rectum (RECTOVAGINAL FISTULA).		04.5511
Aspiration, Respiratory
[description not available]		02.2510
Myoclonic Jerk
[description not available]		02.2510
Cancer of Spleen
[description not available]		04.4680
Bonnevie-Ullrich Syndrome
This syndrome that was originally observed by Ullrich, and designated as identical to TURNER SYNDROME, related the webbing of the neck, loose skin and other anomalies of the syndrome to accumulation of fluid in the embryo starting at the head and dispersing to the extremities (as observed by Bonnevie in mice). Commonly observed at birth in Turner Syndrome and NOONAN SYNDROME; EDEMA of the extremities usually recedes by one year and is an early sign of Turner syndrome, especially in female neonates.		02.2510
Turner Syndrome
A syndrome of defective gonadal development in phenotypic females associated with the karyotype 45,X (or 45,XO). Patients generally are of short stature with undifferentiated GONADS (streak gonads), SEXUAL INFANTILISM, HYPOGONADISM, webbing of the neck, cubitus valgus, elevated GONADOTROPINS, decreased ESTRADIOL level in blood, and CONGENITAL HEART DEFECTS. NOONAN SYNDROME (also called Pseudo-Turner Syndrome and Male Turner Syndrome) resembles this disorder; however, it occurs in males and females with a normal karyotype and is inherited as an autosomal dominant.		07.2510
Dendritic Cell Sarcoma, Follicular
Sarcoma of FOLLICULAR DENDRITIC CELLS most often found in the lymph nodes. This rare neoplasm occurs predominately in adults.		02.2510
Intradural-Extramedullary Spinal Cord Neoplasms
[description not available]		09.66194
Spinal Cord Neoplasms
Benign and malignant neoplasms which occur within the substance of the spinal cord (intramedullary neoplasms) or in the space between the dura and spinal cord (intradural extramedullary neoplasms). The majority of intramedullary spinal tumors are primary CNS neoplasms including ASTROCYTOMA; EPENDYMOMA; and LIPOMA. Intramedullary neoplasms are often associated with SYRINGOMYELIA. The most frequent histologic types of intradural-extramedullary tumors are MENINGIOMA and NEUROFIBROMA.		09.66194
Cochlear Hearing Loss
[description not available]		06.92260
Hearing Loss, Sensorineural
Hearing loss resulting from damage to the COCHLEA and the sensorineural elements which lie internally beyond the oval and round windows. These elements include the AUDITORY NERVE and its connections in the BRAINSTEM.		06.92260
Precordial Catch
[description not available]		02.9640
Blood Pressure, Low
[description not available]		06.8493
Drop Attack
[description not available]		02.5920
Chest Pain
Pressure, burning, or numbness in the chest.		02.9640
Hypotension
Abnormally low BLOOD PRESSURE that can result in inadequate blood flow to the brain and other vital organs. Common symptom is DIZZINESS but greater negative impacts on the body occur when there is prolonged depravation of oxygen and nutrients.		011.8493
Syncope
A transient loss of consciousness and postural tone caused by diminished blood flow to the brain (i.e., BRAIN ISCHEMIA). Presyncope refers to the sensation of lightheadedness and loss of strength that precedes a syncopal event or accompanies an incomplete syncope. (From Adams et al., Principles of Neurology, 6th ed, pp367-9)		02.5920
Palmoplantaris Pustulosis
[description not available]		02.4820
Psoriasis
A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis.		07.4820
Mast Cell Activation Disease
[description not available]		02.3110
Mastocytosis
A rare neoplastic disorder characterized by a clonal proliferation of MAST CELLS, associated with KIT-D816 mutations, and accompanied by aberrant mast cell activation. The abnormal increase of MAST CELLS may occur in only the skin (MASTOCYTOSIS, CUTANEOUS), in extracutaneous tissues involving multiple organs (MASTOCYTOSIS, SYSTEMIC), or in solid tumors (MASTOCYTOMA).		02.3110
Deficiency, Magnesium
[description not available]		05.3540
Magnesium Deficiency
A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. (Harrison's Principles of Internal Medicine, 12th ed, p1936)		05.3540
Osteoradionecrosis
Necrosis of bone following radiation injury.		02.4920
Age-Related Macular Degeneration
[description not available]		03.711
Macular Degeneration
Degenerative changes in the RETINA usually of older adults which results in a loss of vision in the center of the visual field (the MACULA LUTEA) because of damage to the retina. It occurs in dry and wet forms.		03.711
Chemotherapy-Induced Acral Erythema
[description not available]		05.1852
ATLL
[description not available]		011.43217
Leukemia-Lymphoma, Adult T-Cell
Aggressive T-Cell malignancy with adult onset, caused by HUMAN T-LYMPHOTROPIC VIRUS 1. It is endemic in Japan, the Caribbean basin, Southeastern United States, Hawaii, and parts of Central and South America and sub-Saharan Africa.		011.43217
Hand-Foot Syndrome
Chemotherapy-induced dermal side effects that are associated with the use of various CYTOSTATIC AGENTS. Symptoms range from mild ERYTHEMA and/or PARESTHESIA to severe ulcerative dermatitis with debilitating pain involving typically palmoplantar and intertriginous areas. These cutaneous manifestations are sometimes accompanied by nail anomalies.		05.1852
Hyperplasia
An increase in the number of cells in a tissue or organ without tumor formation. It differs from HYPERTROPHY, which is an increase in bulk without an increase in the number of cells.		010.2441
Deafness, Sudden
Complete sensorineural hearing loss which develops suddenly over a period of hours or a few days.		02.2510
Lymphoma of Mucosa-Associated Lymphoid Tissue
[description not available]		02.8130
Lymphoma, B-Cell, Marginal Zone
Extranodal lymphoma of lymphoid tissue associated with mucosa that is in contact with exogenous antigens. Many of the sites of these lymphomas, such as the stomach, salivary gland, and thyroid, are normally devoid of lymphoid tissue. They acquire mucosa-associated lymphoid tissue (MALT) type as a result of an immunologically mediated disorder.		02.8130
Electron Transport Chain Deficiencies, Mitochondrial
[description not available]		02.3110
Nephritis
Inflammation of any part of the KIDNEY.		02.9740
Mitochondrial Diseases
Diseases caused by abnormal function of the MITOCHONDRIA. They may be caused by mutations, acquired or inherited, in mitochondrial DNA or in nuclear genes that code for mitochondrial components. They may also be the result of acquired mitochondria dysfunction due to adverse effects of drugs, infections, or other environmental causes.		02.3110
Ascites, Gelatinous
[description not available]		03.6730
Pseudomyxoma Peritonei
A peritoneal adenocarcinoma characterized by build-up of MUCUS in the PERITONEAL CAVITY. Mucus secreting cells may attach to the peritoneal lining and continue to secrete mucus. The majority of cases represent tumor spread from a primary low-grade mucinous neoplasm of the APPENDIX (NCI Thesaurus).		03.6730
Nasal Septal Perforation
An opening or hole in the NASAL SEPTUM that is caused by TRAUMA, injury, drug use, or pathological process.		02.3110
Neuropathy, Paraneoplastic
[description not available]		05.4551
Anaplastic Oligodendroglioma
[description not available]		09.25197
Oligodendroglioma
A relatively slow-growing glioma that is derived from oligodendrocytes and tends to occur in the cerebral hemispheres, thalamus, or lateral ventricle. They may present at any age, but are most frequent in the third to fifth decades, with an earlier incidence peak in the first decade. Histologically, these tumors are encapsulated, relatively avascular, and tend to form cysts and microcalcifications. Neoplastic cells tend to have small round nuclei surrounded by unstained nuclei. The tumors may vary from well-differentiated to highly anaplastic forms. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2052; Adams et al., Principles of Neurology, 6th ed, p655)		09.25197
Hypercoagulability
[description not available]		03.730
Thrombophilia
A disorder of HEMOSTASIS in which there is a tendency for the occurrence of THROMBOSIS.		03.730
Cystadenocarcinoma, Papillary
An adenocarcinoma in which the tumor elements are arranged as finger-like processes or as a solid spherical nodule projecting from an epithelial surface.		010.5435
Blood Diseases
[description not available]		017.4915089
Chemotherapy-Induced Febrile Neutropenia
FEVER accompanied by a significant reduction in NEUTROPHIL count associated with CHEMOTHERAPY.		014.333932
Hematologic Diseases
Disorders of the blood and blood forming tissues.		017.4915089
Malnourishment
[description not available]		02.5320
Malnutrition
An imbalanced nutritional status resulting from insufficient intake of nutrients to meet normal physiological requirement.		02.5320
DIPG Brain Tumors
[description not available]		02.3110
Diffuse Intrinsic Pontine Glioma
A rare, aggressive brain tumor that forms in the GLIAL CELLS in the PONS.		07.3110
Leukemia, Lymphoblastic, Acute, T Cell
[description not available]		02.3110
Infection Reactivation
[description not available]		02.3110
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
A leukemia/lymphoma found predominately in children and young adults and characterized LYMPHADENOPATHY and THYMUS GLAND involvement. It most frequently presents as a lymphoma, but a leukemic progression in the bone marrow is common.		02.3110
Neoplasms, Skull
[description not available]		04.0450
Injuries, Radiation
[description not available]		014.476631
Eccrine Porocarcinoma
A rare malignant neoplasm of the sweat glands. It most often develops as a form of degenerative progression from a benign ECCRINE POROMA.		02.5820
Cystadenocarcinoma, Mucinous
A malignant cystic or semisolid tumor most often occurring in the ovary. Rarely, one is solid. This tumor may develop from a mucinous cystadenoma, or it may be malignant at the onset. The cysts are lined with tall columnar epithelial cells; in others, the epithelium consists of many layers of cells that have lost normal structure entirely. In the more undifferentiated tumors, one may see sheets and nests of tumor cells that have very little resemblance to the parent structure. (Hughes, Obstetric-Gynecologic Terminology, 1972, p184)		07.63132
Bronchospasm
[description not available]		03.3820
Hemorrhage, Vitreous
[description not available]		03.520
Bronchial Spasm
Spasmodic contraction of the smooth muscle of the bronchi.		03.3820
Vitreous Hemorrhage
Hemorrhage into the VITREOUS BODY.		03.520
Multiple Primary Neoplasms
[description not available]		09.7462
Leucocythaemia
[description not available]		010.37309
Leukemia
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)		010.37309
Envenomation, Snakebite
[description not available]		02.3110
Coagulation, Disseminated Intravascular
[description not available]		02.3110
Enterocolitis, Neutropenic
A syndrome characterized by inflammation in the ILEUM, the CECUM, and the ASCENDING COLON. It is observed in cancer patients with CHEMOTHERAPY-induced NEUTROPENIA or in other immunocompromised individuals (IMMUNOCOMPROMISED HOST).		02.5320
Disseminated Intravascular Coagulation
A disorder characterized by procoagulant substances entering the general circulation causing a systemic thrombotic process. The activation of the clotting mechanism may arise from any of a number of disorders. A majority of the patients manifest skin lesions, sometimes leading to PURPURA FULMINANS.		02.3110
Cancer of Granulosa Cells
[description not available]		04.5651
Central Nervous System Neoplasm
[description not available]		012.184616
Central Nervous System Neoplasms
Benign and malignant neoplastic processes that arise from or secondarily involve the brain, spinal cord, or meninges.		012.184616
Experimental Mammary Neoplasms
[description not available]		06.2200
Superior Vena Cava Obstruction
[description not available]		03.1350
Vascular Fistula
An abnormal passage between two or more BLOOD VESSELS, between ARTERIES; VEINS; or between an artery and a vein.		02.3110
Angiosarcoma
[description not available]		03.0240
Hemangiosarcoma
A rare malignant neoplasm characterized by rapidly proliferating, extensively infiltrating, anaplastic cells derived from blood vessels and lining irregular blood-filled or lumpy spaces. (Stedman, 25th ed)		08.0240
EBV Infections
[description not available]		04.2660
Libman-Sacks Disease
[description not available]		02.8430
Lupus Erythematosus, Systemic
A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys, and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.		02.8430
Epstein-Barr Virus Infections
Infection with human herpesvirus 4 (HERPESVIRUS 4, HUMAN); which may facilitate the development of various lymphoproliferative disorders. These include BURKITT LYMPHOMA (African type), INFECTIOUS MONONUCLEOSIS, and oral hairy leukoplakia (LEUKOPLAKIA, HAIRY).		04.2660
Esophageal Stricture
[description not available]		09.6932
Esophageal Stenosis
A stricture of the ESOPHAGUS. Most are acquired but can be congenital.		04.6932
Lymphocytopenia
[description not available]		04.7161
Lymphopenia
Reduction in the number of lymphocytes.		04.7161
Neoplasms, Bronchial
[description not available]		06.03101
Bronchial Neoplasms
Tumors or cancer of the BRONCHI.		06.03101
Anaplastic Astrocytoma
[description not available]		017.795819
Astrocytoma
Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)		012.795819
Myoepithelial Tumor
[description not available]		02.7830
Myoepithelioma
A usually benign tumor made up predominantly of myoepithelial cells.		07.7830
Rhabdomyolysis
Necrosis or disintegration of skeletal muscle often followed by myoglobinuria.		07.1510
Biliary Tract Cancer
[description not available]		07.6854
Biliary Tract Neoplasms
Tumors or cancer in the BILIARY TRACT including the BILE DUCTS and the GALLBLADDER.		07.6854
Kidney Diseases
Pathological processes of the KIDNEY or its component tissues.		012.027415
Benign Meningeal Neoplasms
[description not available]		04.03140
Meningeal Neoplasms
Benign and malignant neoplastic processes that arise from or secondarily involve the meningeal coverings of the brain and spinal cord.		04.03140
Hand Dermatosis
[description not available]		02.1510
Hand Dermatoses
Skin diseases involving the HANDS.		02.1510
Hypopharyngeal Cancer
[description not available]		016.763420
Hypopharyngeal Neoplasms
Tumors or cancer of the HYPOPHARYNX.		011.763420
Bone Marrow Diseases
Diseases involving the BONE MARROW.		011.944517
Cancer of Gastrointestinal Tract
[description not available]		08.69114
Lactic Acidosis
[description not available]		07.520
Bewilderment
[description not available]		02.5420
Agitation, Psychomotor
[description not available]		02.1510
Deficiency, Thiamine
[description not available]		02.1510
Acidosis, Lactic
Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE.		02.520
Psychomotor Agitation
A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.		02.1510
Thiamine Deficiency
A nutritional condition produced by a deficiency of THIAMINE in the diet, characterized by anorexia, irritability, and weight loss. Later, patients experience weakness, peripheral neuropathy, headache, and tachycardia. In addition to being caused by a poor diet, thiamine deficiency in the United States most commonly occurs as a result of alcoholism, since ethanol interferes with thiamine absorption. In countries relying on polished rice as a dietary staple, BERIBERI prevalence is very high. (From Cecil Textbook of Medicine, 19th ed, p1171)		02.1510
Nervous System Disorders
[description not available]		013.23121
Nervous System Diseases
Diseases of the central and peripheral nervous system. This includes disorders of the brain, spinal cord, cranial nerves, peripheral nerves, nerve roots, autonomic nervous system, neuromuscular junction, and muscle.		013.23121
Carcinoma, Basal Cell, Pigmented
[description not available]		06.262
Carcinoma, Basal Cell
A malignant skin neoplasm that seldom metastasizes but has potentialities for local invasion and destruction. Clinically it is divided into types: nodular, cicatricial, morphaic, and erythematoid (pagetoid). They develop on hair-bearing skin, most commonly on sun-exposed areas. Approximately 85% are found on the head and neck area and the remaining 15% on the trunk and limbs. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1471)		06.262
Central Hypothyroidism
[description not available]		07.4252
Hypothyroidism
A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA. It may be primary or secondary due to other pituitary disease, or hypothalamic dysfunction.		012.4252
Lupus Erythematosus, Cutaneous, Subacute
[description not available]		02.5220
Lupus Erythematosus, Cutaneous
A form of lupus erythematosus in which the skin may be the only organ involved or in which skin involvement precedes the spread into other body systems. It has been classified into three forms - acute (= LUPUS ERYTHEMATOSUS, SYSTEMIC with skin lesions), subacute, and chronic (= LUPUS ERYTHEMATOSUS, DISCOID).		02.5220
Cushing's Syndrome
[description not available]		03.3420
Cancer of Pituitary
[description not available]		04.74110
Cushing Syndrome
A condition caused by prolonged exposure to excess levels of cortisol (HYDROCORTISONE) or other GLUCOCORTICOIDS from endogenous or exogenous sources. It is characterized by upper body OBESITY; OSTEOPOROSIS; HYPERTENSION; DIABETES MELLITUS; HIRSUTISM; AMENORRHEA; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of ADRENOCORTICOTROPIN and those that are ACTH-independent.		03.3420
Pituitary Neoplasms
Neoplasms which arise from or metastasize to the PITUITARY GLAND. The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (see ADENOMA, BASOPHIL; ADENOMA, ACIDOPHIL; and ADENOMA, CHROMOPHOBE). Pituitary tumors may compress adjacent structures, including the HYPOTHALAMUS, several CRANIAL NERVES, and the OPTIC CHIASM. Chiasmal compression may result in bitemporal HEMIANOPSIA.		04.74110
Diarrhea
An increased liquidity or decreased consistency of FECES, such as running stool. Fecal consistency is related to the ratio of water-holding capacity of insoluble solids to total water, rather than the amount of water present. Diarrhea is not hyperdefecation or increased fecal weight.		019.365339
Cancer of Eye
[description not available]		09.97407
Infarct
[description not available]		07.4620
Cancer of Sigmoid
[description not available]		02.8330
Glomerulonephritis, Minimal Change
[description not available]		02.7730
Paraneoplastic Syndromes
In patients with neoplastic diseases a wide variety of clinical pictures which are indirect and usually remote effects produced by tumor cell metabolites or other products.		05.54160
Cold Panniculitis
[description not available]		02.4820
Nephrosis, Lipoid
A kidney disease with no or minimal histological glomerular changes on light microscopy and with no immune deposits. It is characterized by lipid accumulation in the epithelial cells of KIDNEY TUBULES and in the URINE. Patients usually show NEPHROTIC SYNDROME indicating the presence of PROTEINURIA with accompanying EDEMA.		02.7730
Nephrotic Syndrome
A condition characterized by severe PROTEINURIA, greater than 3.5 g/day in an average adult. The substantial loss of protein in the urine results in complications such as HYPOPROTEINEMIA; generalized EDEMA; HYPERTENSION; and HYPERLIPIDEMIAS. Diseases associated with nephrotic syndrome generally cause chronic kidney dysfunction.		02.830
47,XX,+21
[description not available]		03.3520
Down Syndrome
A chromosome disorder associated either with an extra chromosome 21 or an effective trisomy for chromosome 21. Clinical manifestations include hypotonia, short stature, brachycephaly, upslanting palpebral fissures, epicanthus, Brushfield spots on the iris, protruding tongue, small ears, short, broad hands, fifth finger clinodactyly, Simian crease, and moderate to severe INTELLECTUAL DISABILITY. Cardiac and gastrointestinal malformations, a marked increase in the incidence of LEUKEMIA, and the early onset of ALZHEIMER DISEASE are also associated with this condition. Pathologic features include the development of NEUROFIBRILLARY TANGLES in neurons and the deposition of AMYLOID BETA-PROTEIN, similar to the pathology of ALZHEIMER DISEASE. (Menkes, Textbook of Child Neurology, 5th ed, p213)		03.3520
Bone Diseases
Diseases of BONES.		02.1510
Lethargy
A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to DEPRESSION or DRUG ADDICTION.		03.5311
Nasal Bleeding
[description not available]		05.8242
Epistaxis
Bleeding from the nose.		05.8242
Cardiac Cancer
[description not available]		03.92120
Amaurosis Fugax
Transient complete or partial monocular blindness due to retinal ischemia. This may be caused by emboli from the CAROTID ARTERY (usually in association with CAROTID STENOSIS) and other locations that enter the central RETINAL ARTERY. (From Adams et al., Principles of Neurology, 6th ed, p245)		02.1710
Hemoptysis
Expectoration or spitting of blood originating from any part of the RESPIRATORY TRACT, usually from hemorrhage in the lung parenchyma (PULMONARY ALVEOLI) and the BRONCHIAL ARTERIES.		05.6461
Cancer of the Vagina
[description not available]		05.39130
Vaginal Neoplasms
Tumors or cancer of the VAGINA.		05.39130
Melanoameloblastoma
[description not available]		02.4920
Embryopathies
[description not available]		02.4620
Infant, Newborn, Diseases
Diseases of newborn infants present at birth (congenital) or developing within the first month of birth. It does not include hereditary diseases not manifesting at birth or within the first 30 days of life nor does it include inborn errors of metabolism. Both HEREDITARY DISEASES and METABOLISM, INBORN ERRORS are available as general concepts.		02.1710
Breast Cancer, Male
[description not available]		05.6232
Breast Neoplasms, Male
Any neoplasms of the male breast. These occur infrequently in males in developed countries, the incidence being about 1% of that in females.		05.6232
Fibromatosis
[description not available]		02.5220
Fibroma
A benign tumor of fibrous or fully developed connective tissue.		02.5220
Fibrosarcoma
A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)		06.38151
Agranulocytosis
A decrease in the number of GRANULOCYTES; (BASOPHILS; EOSINOPHILS; and NEUTROPHILS).		08.39118
Infusion Site Adverse Event
[description not available]		02.1710
Brain Stem Neoplasms, Primary
[description not available]		08.96225
Brain Stem Neoplasms
Benign and malignant intra-axial tumors of the MESENCEPHALON; PONS; or MEDULLA OBLONGATA of the BRAIN STEM. Primary and metastatic neoplasms may occur in this location. Clinical features include ATAXIA, cranial neuropathies (see CRANIAL NERVE DISEASES), NAUSEA, hemiparesis (see HEMIPLEGIA), and quadriparesis. Primary brain stem neoplasms are more frequent in children. Histologic subtypes include GLIOMA; HEMANGIOBLASTOMA; GANGLIOGLIOMA; and EPENDYMOMA.		08.96225
Thromboembolism
Obstruction of a blood vessel (embolism) by a blood clot (THROMBUS) in the blood stream.		012.6594
Hyperoxia
An abnormal increase in the amount of oxygen in the tissues and organs.		07.1710
Adenoma Sebaceum
Facial ANGIOFIBROMA in tuberous sclerosis		02.1710
Tuberous Sclerosis
Autosomal dominant neurocutaneous syndrome classically characterized by MENTAL RETARDATION; EPILEPSY; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and HAMARTOMAS formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.		02.1710
Disgerminoma
[description not available]		09.61295
Dysgerminoma
A malignant ovarian neoplasm, thought to be derived from primordial germ cells of the sexually undifferentiated embryonic gonad. It is the counterpart of the classical seminoma of the testis, to which it is both grossly and histologically identical. Dysgerminomas comprise 16% of all germ cell tumors but are rare before the age of 10, although nearly 50% occur before the age of 20. They are generally considered of low-grade malignancy but may spread if the tumor extends through its capsule and involves lymph nodes or blood vessels. (Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1646)		09.61295
Hyperglycemia, Postprandial
Abnormally high BLOOD GLUCOSE level after a meal.		05.152
Hyperglycemia
Abnormally high BLOOD GLUCOSE level.		010.152
Vestibular Diseases
Pathological processes of the VESTIBULAR LABYRINTH which contains part of the balancing apparatus. Patients with vestibular diseases show instability and are at risk of frequent falls.		02.4320
Carcinoma, Mucoepidermoid
A tumor of both low- and high-grade malignancy. The low-grade grow slowly, appear in any age group, and are readily cured by excision. The high-grade behave aggressively, widely infiltrate the salivary gland and produce lymph node and distant metastases. Mucoepidermoid carcinomas account for about 21% of the malignant tumors of the parotid gland and 10% of the sublingual gland. They are the most common malignant tumor of the parotid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575; Holland et al., Cancer Medicine, 3d ed, p1240)		03.0440
Cancer of Pelvis
[description not available]		07.68192
Actinic Keratosis
[description not available]		03.4420
Keratosis, Actinic
White or pink lesions on the arms, hands, face, or scalp that arise from sun-induced DNA DAMAGE to KERATINOCYTES in exposed areas. They are considered precursor lesions to superficial SQUAMOUS CELL CARCINOMA.		03.4420
Androblastoma
[description not available]		03.8940
Thrombotic Microangiopathies
Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.		03.9121
Retinal Pigment Epithelial Detachment
[description not available]		05.7371
Retinal Detachment
Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12).		05.7371
Buphthalmos
[description not available]		02.7630
Neoplasms, Bone Marrow
[description not available]		07.57123
Bone Marrow Neoplasms
Neoplasms located in the bone marrow. They are differentiated from neoplasms composed of bone marrow cells, such as MULTIPLE MYELOMA. Most bone marrow neoplasms are metastatic.		07.57123
Cancer of ILEUM
[description not available]		02.4720
Dental Tissue Neoplasms
[description not available]		02.5220
Mandibular Neoplasms
Tumors or cancer of the MANDIBLE.		03.1250
Ameloblastoma
An immature epithelial tumor of the JAW originating from the epithelial rests of Malassez or from other epithelial remnants of the ENAMEL from the developmental period. It is a slowly growing tumor, usually benign, but displays a marked propensity for invasive growth.		07.9440
Gastritis
Inflammation of the GASTRIC MUCOSA, a lesion observed in a number of unrelated disorders.		02.4520
Angiogenesis, Pathologic
[description not available]		013.375810
Complex and Mixed Neoplasms
[description not available]		02.5220
Neoplasms, Complex and Mixed
Neoplasms composed of more than one type of neoplastic tissue.		02.5220
Hypergonadotropic Hypogonadism
[description not available]		03.9240
Sterility, Male
[description not available]		0560
Disease, Pulmonary
[description not available]		09.51164
Hypogonadism
Condition resulting from deficient gonadal functions, such as GAMETOGENESIS and the production of GONADAL STEROID HORMONES. It is characterized by delay in GROWTH, germ cell maturation, and development of secondary sex characteristics. Hypogonadism can be due to a deficiency of GONADOTROPINS (hypogonadotropic hypogonadism) or due to primary gonadal failure (hypergonadotropic hypogonadism).		03.9240
Infertility, Male
The inability of the male to effect FERTILIZATION of an OVUM after a specified period of unprotected intercourse. Male sterility is permanent infertility.		0560
Lung Diseases
Pathological processes involving any part of the LUNG.		09.51164
Infection
[description not available]		08.64148
Infections
Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases.		08.64148
Acquired Autoimmune Hemolytic Anemia
[description not available]		0340
Anemia, Hemolytic, Autoimmune
Acquired hemolytic anemia due to the presence of AUTOANTIBODIES which agglutinate or lyse the patient's own RED BLOOD CELLS.		0340
Embolism, Pulmonary
[description not available]		03.6730
Pulmonary Embolism
Blocking of the PULMONARY ARTERY or one of its branches by an EMBOLUS.		03.6730
Bacterial Pneumonia
[description not available]		02.4320
Atypical Mycobacterial Infection, Disseminated
[description not available]		02.1710
Pneumonia, Bacterial
Inflammation of the lung parenchyma that is caused by bacterial infections.		02.4320
Intestinal Diseases
Pathological processes in any segment of the INTESTINE from DUODENUM to RECTUM.		03.0910
Animal Mammary Carcinoma
[description not available]		05.5761
Eyelid Diseases
Diseases involving the EYELIDS.		02.7830
Chromosome Instability Syndromes
[description not available]		02.6120
Anaplastic Large-Cell Lymphoma
[description not available]		02.2110
Cancer of the Tonsil
[description not available]		04.3441
Tonsillar Neoplasms
Tumors or cancer of the PALATINE TONSIL.		04.3441
Lymphoma, Large-Cell, Anaplastic
A systemic, large-cell, non-Hodgkin, malignant lymphoma characterized by cells with pleomorphic appearance and expressing the CD30 ANTIGEN. These so-called hallmark cells have lobulated and indented nuclei. This lymphoma is often mistaken for metastatic carcinoma and MALIGNANT HISTIOCYTOSIS.		02.2110
Enlarged Liver
[description not available]		07.2951
Neoplasms, Otorhinolaryngologic
[description not available]		08.49166
Cancer, Radiation-Induced
[description not available]		05.9491
Eaton-Lambert Myasthenic Syndrome
[description not available]		03.2960
Lambert-Eaton Myasthenic Syndrome
An autoimmune disease characterized by weakness and fatigability of proximal muscles, particularly of the pelvic girdle, lower extremities, trunk, and shoulder girdle. There is relative sparing of extraocular and bulbar muscles. CARCINOMA, SMALL CELL of the lung is a frequently associated condition, although other malignancies and autoimmune diseases may be associated. Muscular weakness results from impaired impulse transmission at the NEUROMUSCULAR JUNCTION. Presynaptic calcium channel dysfunction leads to a reduced amount of acetylcholine being released in response to stimulation of the nerve. (From Adams et al., Principles of Neurology, 6th ed, pp 1471)		03.2960
Meigs Syndrome
The triad of benign FIBROMA or other ovarian tumors with ASCITES, and HYDROTHORAX due to large PLEURAL EFFUSIONS.		02.2110
Pleural Effusion
Presence of fluid in the pleural cavity resulting from excessive transudation or exudation from the pleural surfaces. It is a sign of disease and not a diagnosis in itself.		010.76112
Fistula
Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body.		02.1710
HIV
Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2.		04.8221
Hematologic Malignancies
[description not available]		05.2362
Hematologic Neoplasms
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.		05.2362
Uveal Neoplasms
Tumors or cancer of the UVEA.		05.7571
Cancer of Pharynx
[description not available]		07.66122
Pharyngeal Neoplasms
Tumors or cancer of the PHARYNX.		07.66122
Atelectasis
[description not available]		02.2110
Epiphora
[description not available]		02.5720
Lacrimal Apparatus Diseases
Diseases of the LACRIMAL APPARATUS.		02.5720
Glaucoma, Neovascular
A form of secondary glaucoma which develops as a consequence of another ocular disease and is attributed to the forming of new vessels in the angle of the anterior chamber.		02.7330
Cancer of Parotid
[description not available]		02.9840
Parotid Neoplasms
Tumors or cancer of the PAROTID GLAND.		02.9840
Hypophosphatemia
A condition of an abnormally low level of PHOSPHATES in the blood.		06.6541
Dermatoses
[description not available]		05.4651
Skin Diseases
Diseases involving the DERMIS or EPIDERMIS.		05.4651
Cardiac Tamponade
Compression of the heart by accumulated fluid (PERICARDIAL EFFUSION) or blood (HEMOPERICARDIUM) in the PERICARDIUM surrounding the heart. The affected cardiac functions and CARDIAC OUTPUT can range from minimal to total hemodynamic collapse.		09.551
Abdominal Neoplasms
New abnormal growth of tissue in the ABDOMEN.		010.45297
Hypercalciuria
Excretion of abnormally high level of CALCIUM in the URINE, greater than 4 mg/kg/day.		02.2110
Kidney Tubular Transport, Inborn Error
[description not available]		02.2110
Nephrocalcinosis
A condition characterized by calcification of the renal tissue itself. It is usually seen in distal RENAL TUBULAR ACIDOSIS with calcium deposition in the DISTAL KIDNEY TUBULES and the surrounding interstitium. Nephrocalcinosis causes RENAL INSUFFICIENCY.		02.2110
Carcinomatous Meningitis
[description not available]		03.0240
Meningeal Carcinomatosis
Primary or secondary neoplasm in the ARACHNOID or SUBARACHNOID SPACE. It appears as a diffuse fibrotic thickening of the MENINGES associated with variable degrees of inflammation.		08.0240
Rhabdomyosarcoma 2
[description not available]		02.2110
Cancer of Muscle
[description not available]		04.3641
Rhabdomyosarcoma, Alveolar
A form of RHABDOMYOSARCOMA occurring mainly in adolescents and young adults, affecting muscles of the extremities, trunk, orbital region, etc. It is extremely malignant, metastasizing widely at an early stage. Few cures have been achieved and the prognosis is poor. Alveolar refers to its microscopic appearance simulating the cells of the respiratory alveolus. (Holland et al., Cancer Medicine, 3d ed, p2188)		02.2110
Anaplastic Ependymoma
[description not available]		06.59144
Ependymoma
Glioma derived from EPENDYMOGLIAL CELLS that tend to present as malignant intracranial tumors in children and as benign intraspinal neoplasms in adults. It may arise from any level of the ventricular system or central canal of the spinal cord. Intracranial ependymomas most frequently originate in the FOURTH VENTRICLE and histologically are densely cellular tumors which may contain ependymal tubules and perivascular pseudorosettes. Spinal ependymomas are usually benign papillary or myxopapillary tumors. (From DeVita et al., Principles and Practice of Oncology, 5th ed, p2018; Escourolle et al., Manual of Basic Neuropathology, 2nd ed, pp28-9)		06.59144
Acute Pain
Intensely discomforting, distressful, or agonizing sensation associated with trauma or disease, with well-defined location, character, and timing.		02.2510
Atrophy, Muscular, Peroneal
[description not available]		02.2110
Charcot-Marie-Tooth Disease
A hereditary motor and sensory neuropathy transmitted most often as an autosomal dominant trait and characterized by progressive distal wasting and loss of reflexes in the muscles of the legs (and occasionally involving the arms). Onset is usually in the second to fourth decade of life. This condition has been divided into two subtypes, hereditary motor and sensory neuropathy (HMSN) types I and II. HMSN I is associated with abnormal nerve conduction velocities and nerve hypertrophy, features not seen in HMSN II. (Adams et al., Principles of Neurology, 6th ed, p1343)		02.2110
Chromosomal Translocation
[description not available]		06.87110
IgG4 Related Systemic Disease
[description not available]		02.2110
Immunoglobulin G4-Related Disease
A spectrum of systemic autoimmune diseases in which IMMUNOGLOBULIN G4 plays a pathophysiologic role. It can affect multiple organs in highly variable presentations, characterized by inflammatory lesions composed of IgG4-positive PLASMA CELLS, further infiltrated by T helper cells (T-LYMPHOCYTES, HELPER-INDUCER) when linked to progressive FIBROSIS and eventual organ damage.		02.2110
Conus Medullaris Syndrome
[description not available]		03.1550
Hypermelanosis
[description not available]		05.2741
Hyperpigmentation
Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance.		05.2741
African Lymphoma
[description not available]		04.7971
Burkitt Lymphoma
A form of undifferentiated malignant LYMPHOMA usually found in central Africa, but also reported in other parts of the world. It is commonly manifested as a large osteolytic lesion in the jaw or as an abdominal mass. B-cell antigens are expressed on the immature cells that make up the tumor in virtually all cases of Burkitt lymphoma. The Epstein-Barr virus (HERPESVIRUS 4, HUMAN) has been isolated from Burkitt lymphoma cases in Africa and it is implicated as the causative agent in these cases; however, most non-African cases are EBV-negative.		04.7971
Emergencies
Situations or conditions requiring immediate intervention to avoid serious adverse results.		04.2260
Allodynia
[description not available]		02.7830
Respiration Disorders
Diseases of the respiratory system in general or unspecified or for a specific respiratory disease not available.		04.7921
Late Onset Diseases
[description not available]		02.2110
Vascular Diseases
Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.		02.8330
Ganglioneuroblastoma
A moderately malignant neoplasm composed of primitive neuroectodermal cells dispersed in myxomatous or fibrous stroma intermixed with mature ganglion cells. It may undergo transformation into a neuroblastoma. It arises from the sympathetic trunk or less frequently from the adrenal medulla, cerebral cortex, and other locations. Cervical ganglioneuroblastomas may be associated with HORNER SYNDROME and the tumor may occasionally secrete vasoactive intestinal peptide, resulting in chronic diarrhea.		03.1750
Pyomyositis
An intramuscular suppuration of the large skeletal muscle groups. It is associated with INFECTION such as STAPHYLOCOCCUS AUREUS and PYODERMA. It was known as a tropical disease but is increasing among the immunocompromised (IMMUNOCOMPROMISED HOST). Symptoms include muscle pain, FEVER, and leucocytosis. It has been diagnosed by MRI SCANS.		02.4720
Abscess
Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection.		02.4920
Hematemesis
Vomiting of blood that is either fresh bright red, or older coffee-ground in character. It generally indicates bleeding of the UPPER GASTROINTESTINAL TRACT.		02.0810
Paraparesis
Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of SPINAL CORD DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; MUSCULAR DISEASES; INTRACRANIAL HYPERTENSION; parasagittal brain lesions; and other conditions.		03.3820
Colonic Inertia
Symptom characterized by the passage of stool once a week or less.		06.5463
Anus Prolapse
[description not available]		02.0810
Peripheral Nerve Neoplasms
[description not available]		02.9640
Constipation
Infrequent or difficult evacuation of FECES. These symptoms are associated with a variety of causes, including low DIETARY FIBER intake, emotional or nervous disturbances, systemic and structural disorders, drug-induced aggravation, and infections.		06.5463
Peripheral Nervous System Neoplasms
Neoplasms which arise from peripheral nerve tissue. This includes NEUROFIBROMAS; SCHWANNOMAS; GRANULAR CELL TUMORS; and malignant peripheral NERVE SHEATH NEOPLASMS. (From DeVita Jr et al., Cancer: Principles and Practice of Oncology, 5th ed, pp1750-1)		02.9640
Dysarthosis
[description not available]		02.0810
Flaccid Quadriplegia
[description not available]		02.7130
Anterior Horn Cell Disease
[description not available]		02.4720
Motor Neuron Disease
Diseases characterized by a selective degeneration of the motor neurons of the spinal cord, brainstem, or motor cortex. Clinical subtypes are distinguished by the major site of degeneration. In AMYOTROPHIC LATERAL SCLEROSIS there is involvement of upper, lower, and brainstem motor neurons. In progressive muscular atrophy and related syndromes (see MUSCULAR ATROPHY, SPINAL) the motor neurons in the spinal cord are primarily affected. With progressive bulbar palsy (BULBAR PALSY, PROGRESSIVE), the initial degeneration occurs in the brainstem. In primary lateral sclerosis, the cortical neurons are affected in isolation. (Adams et al., Principles of Neurology, 6th ed, p1089)		02.4720
Gastric Fistula
Abnormal passage communicating with the STOMACH.		02.0810
Exophthalmos
Abnormal protrusion of both eyes; may be caused by endocrine gland malfunction, malignancy, injury, or paralysis of the extrinsic muscles of the eye.		02.0810
Dyskinesia Syndromes
[description not available]		02.0810
Sensation Disorders
Disorders of the special senses (i.e., VISION; HEARING; TASTE; and SMELL) or somatosensory system (i.e., afferent components of the PERIPHERAL NERVOUS SYSTEM).		05.8283
Movement Disorders
Syndromes which feature DYSKINESIAS as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions.		02.0810
Alveolitis, Fibrosing
[description not available]		04.7771
Pulmonary Fibrosis
A process in which normal lung tissues are progressively replaced by FIBROBLASTS and COLLAGEN causing an irreversible loss of the ability to transfer oxygen into the bloodstream via PULMONARY ALVEOLI. Patients show progressive DYSPNEA finally resulting in death.		09.7771
Esophageal Diseases
Pathological processes in the ESOPHAGUS.		02.4520
Drug Overdose
Accidental or deliberate use of a medication or street drug in excess of normal dosage.		02.7130
Leukostasis
Abnormal intravascular leukocyte aggregation and clumping often seen in leukemia patients. The brain and lungs are the two most commonly affected organs. This acute syndrome requires aggressive cytoreductive modalities including chemotherapy and/or leukophoresis. It is differentiated from LEUKEMIC INFILTRATION which is a neoplastic process where leukemic cells invade organs.		02.4320
Branch Retinal Artery Occlusion
[description not available]		02.0810
Choroiditis
Inflammation of the choroid.		02.0810
Retinal Artery Occlusion
Sudden ISCHEMIA in the RETINA due to blocked blood flow through the CENTRAL RETINAL ARTERY or its branches leading to sudden complete or partial loss of vision, respectively, in the eye.		02.0810
Argentaffinoma
[description not available]		06.3351
Carcinoid Tumor
A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182)		06.3351
Cardiometabolic Syndrome
A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components not only include metabolic dysfunctions of METABOLIC SYNDROME but also HYPERTENSION, and ABDOMINAL OBESITY.		02.0810
Metabolic Syndrome
A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.		02.0810
Inflammatory Breast Cancer
[description not available]		010.061210
Inflammatory Breast Neoplasms
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.		010.061210
Vulvar Diseases
Pathological processes of the VULVA.		02.0810
Ear Diseases
Pathological processes of the ear, the hearing, and the equilibrium system of the body.		04.9960
Appendiceal Cancer
[description not available]		02.7730
Appendiceal Neoplasms
Tumors or cancer of the APPENDIX.		02.7730
Water-Electrolyte Imbalance
Disturbances in the body's WATER-ELECTROLYTE BALANCE.		02.5220
Antidiuretic Hormone, Inappropriate Secretion
[description not available]		03.9120
Benign Hypothalamic Neoplasms
[description not available]		03.4170
Diabetes Insipidus
A disease that is characterized by frequent urination, excretion of large amounts of dilute URINE, and excessive THIRST. Etiologies of diabetes insipidus include deficiency of antidiuretic hormone (also known as ADH or VASOPRESSIN) secreted by the NEUROHYPOPHYSIS, impaired KIDNEY response to ADH, and impaired hypothalamic regulation of thirst.		02.4620
Inappropriate ADH Syndrome
A condition of HYPONATREMIA and renal salt loss attributed to overexpansion of BODY FLUIDS resulting from sustained release of ANTIDIURETIC HORMONES which stimulates renal resorption of water. It is characterized by normal KIDNEY function, high urine OSMOLALITY, low serum osmolality, and neurological dysfunction. Etiologies include ADH-producing neoplasms, injuries or diseases involving the HYPOTHALAMUS, the PITUITARY GLAND, and the LUNG. This syndrome can also be drug-induced.		03.9120
Chills
The sudden sensation of being cold. It may be accompanied by SHIVERING.		03.4711
Colicky Pain
[description not available]		06.2872
Abdominal Pain
Sensation of discomfort, distress, or agony in the abdominal region.		06.2872
Clubfeet
[description not available]		02.0810
Frigidity
[description not available]		02.0810
Sex Disorders
[description not available]		02.0810
Sexual Dysfunction, Physiological
Physiological disturbances in normal sexual performance in either the male or the female.		02.0810
Sexual Dysfunctions, Psychological
Disturbances in sexual desire and the psychophysiologic changes that characterize the sexual response cycle and cause marked distress and interpersonal difficulty. (APA, DSM-IV, 1994)		02.0810
Cancer of Parathyroid
[description not available]		02.0810
Parathyroid Neoplasms
Tumors or cancer of the PARATHYROID GLANDS.		02.0810
Ewing Sarcoma
[description not available]		07.58154
Synovioma
[description not available]		04.1331
Sarcoma, Ewing
A malignant tumor of the bone which always arises in the medullary tissue, occurring more often in cylindrical bones. The tumor occurs usually before the age of 20, about twice as frequently in males as in females.		07.58154
Sarcoma, Synovial
A malignant neoplasm arising from tenosynovial tissue of the joints and in synovial cells of tendons and bursae. The legs are the most common site, but the tumor can occur in the abdominal wall and other trunk muscles. There are two recognized types: the monophasic (characterized by sheaths of monotonous spindle cells) and the biphasic (characterized by slit-like spaces or clefts within the tumor, lined by cuboidal or tall columnar epithelial cells). These sarcomas occur most commonly in the second and fourth decades of life. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1363)		04.1331
Weight Reduction
[description not available]		08.37236
Weight Loss
Decrease in existing BODY WEIGHT.		08.37236
Dysplastic Nevus Syndrome, Hereditary
[description not available]		04.3911
Glomerulonephritis, Lupus
[description not available]		02.0810
Lupus Nephritis
Glomerulonephritis associated with autoimmune disease SYSTEMIC LUPUS ERYTHEMATOSUS. Lupus nephritis is histologically classified into 6 classes: class I - normal glomeruli, class II - pure mesangial alterations, class III - focal segmental glomerulonephritis, class IV - diffuse glomerulonephritis, class V - diffuse membranous glomerulonephritis, and class VI - advanced sclerosing glomerulonephritis (The World Health Organization classification 1982).		02.0810
Dehydration
The condition that results from excessive loss of water from a living organism.		05.2341
Cachexia
General ill health, malnutrition, and weight loss, usually associated with chronic disease.		09.732
Bilateral Headache
[description not available]		07.41105
Polyradiculitis
[description not available]		02.4520
Headache
The symptom of PAIN in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of HEADACHE DISORDERS.		07.41105
Polyradiculopathy
Disease or injury involving multiple SPINAL NERVE ROOTS. Polyradiculitis refers to inflammation of multiple spinal nerve roots.		02.4520
Milk-Alkali Syndrome
[description not available]		02.9740
Hemorrhage, Uterine
[description not available]		03.6530
Hypercalcemia
Abnormally high level of calcium in the blood.		02.9740
Uterine Hemorrhage
Bleeding from blood vessels in the UTERUS, sometimes manifested as vaginal bleeding.		03.6530
Hypoalbuminemia
A condition in which albumin level in blood (SERUM ALBUMIN) is below the normal range. Hypoalbuminemia may be due to decreased hepatic albumin synthesis, increased albumin catabolism, altered albumin distribution, or albumin loss through the urine (ALBUMINURIA).		02.0810
Taste Disorder, Anterior Tongue
[description not available]		04.3541
Arrhythmia
[description not available]		02.110
Arrhythmias, Cardiac
Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.		02.110
Blood Loss, Surgical
Loss of blood during a surgical procedure.		02.9840
Cancer of Penis
[description not available]		04.8370
Penile Neoplasms
Cancers or tumors of the PENIS or of its component tissues.		04.8370
Pernicious Vomiting of Pregnancy
[description not available]		02.110
Hyperemesis Gravidarum
Intractable VOMITING that develops in early PREGNANCY and persists. This can lead to DEHYDRATION and WEIGHT LOSS.		02.110
6th Nerve Palsy
[description not available]		02.7330
Airway Obstruction
Any hindrance to the passage of air into and out of the lungs.		02.9640
Male Genital Neoplasms
[description not available]		03.821
Genital Neoplasms, Male
Tumor or cancer of the MALE GENITALIA.		03.821
Left Ventricular Dysfunction
[description not available]		0310
Heart Disease, Ischemic
[description not available]		03.3620
Myocardial Ischemia
A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).		03.3620
Ventricular Dysfunction, Left
A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.		0310
Weight Gain
Increase in BODY WEIGHT over existing weight.		02.9340
Delayed Hypersensitivity
[description not available]		08.4270
Antibody Deficiency Syndrome
[description not available]		02.110
Pancytopenia
Deficiency of all three cell elements of the blood, erythrocytes, leukocytes and platelets.		012.94156
Immunologic Deficiency Syndromes
Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.		02.110
Acute Lymphoid Leukemia
[description not available]		010.45209
Precursor Cell Lymphoblastic Leukemia-Lymphoma
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.		010.45209
Extramembranous Glomerulopathy
[description not available]		02.110
Glomerulonephritis, Membranous
A type of glomerulonephritis that is characterized by the accumulation of immune deposits (COMPLEMENT MEMBRANE ATTACK COMPLEX) on the outer aspect of the GLOMERULAR BASEMENT MEMBRANE. It progresses from subepithelial dense deposits, to basement membrane reaction and eventual thickening of the basement membrane.		02.110
Leukocytosis
A transient increase in the number of leukocytes in a body fluid.		02.4520
Petechiae
Pinhead size (3 mm) skin discolorization due to hemorrhage.		03.0110
Angiitis
[description not available]		03.0110
Purpura
Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. When the size of the discolorization is		03.0110
Vasculitis
Inflammation of any one of the blood vessels, including the ARTERIES; VEINS; and rest of the vasculature system in the body.		03.0110
Asymptomatic Conditions
[description not available]		02.110
Cancer of Rectum
[description not available]		09.09201
Rectal Neoplasms
Tumors or cancer of the RECTUM.		09.09201
Abdominal Cryptorchidism
[description not available]		03.6330
Azoospermia
A condition of having no sperm present in the ejaculate (SEMEN).		02.4820
CJD (Creutzfeldt-Jakob Disease)
[description not available]		03.0110
Creutzfeldt-Jakob Syndrome
A rare transmissible encephalopathy most prevalent between the ages of 50 and 70 years. Affected individuals may present with sleep disturbances, personality changes, ATAXIA; APHASIA, visual loss, weakness, muscle atrophy, MYOCLONUS, progressive dementia, and death within one year of disease onset. A familial form exhibiting autosomal dominant inheritance and a new variant CJD (potentially associated with ENCEPHALOPATHY, BOVINE SPONGIFORM) have been described. Pathological features include prominent cerebellar and cerebral cortical spongiform degeneration and the presence of PRIONS. (From N Engl J Med, 1998 Dec 31;339(27))		03.0110
Aneurysm, Anterior Cerebral Artery
[description not available]		02.4620
Angiomyxoma
[description not available]		02.110
Intracranial Aneurysm
Abnormal outpouching in the wall of intracranial blood vessels. Most common are the saccular (berry) aneurysms located at branch points in CIRCLE OF WILLIS at the base of the brain. Vessel rupture results in SUBARACHNOID HEMORRHAGE or INTRACRANIAL HEMORRHAGES. Giant aneurysms (		02.4620
Female Genitourinary Diseases
[description not available]		03.3420
Ataxia
Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.		04.1531
Tracheal Neoplasms
New abnormal growth of tissue in the TRACHEA.		02.7330
Adenoma, Basal Cell
[description not available]		02.5220
Adenohypophyseal Hyposecretion
[description not available]		02.7330
Endotoxin Shock
[description not available]		02.110
Adenoma
A benign epithelial tumor with a glandular organization.		02.5220
Hypopituitarism
Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FOLLICLE STIMULATING HORMONE; SOMATOTROPIN; and CORTICOTROPIN). This may result from surgical or radiation ablation, non-secretory PITUITARY NEOPLASMS, metastatic tumors, infarction, PITUITARY APOPLEXY, infiltrative or granulomatous processes, and other conditions.		02.7330
Shock, Septic
Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status.		02.110
Candidemia
A form of invasive candidiasis where species of CANDIDA are present in the blood.		02.110
Hepatic Insufficiency
Conditions in which the LIVER functions fall below the normal ranges. Severe hepatic insufficiency may cause LIVER FAILURE or DEATH. Treatment may include LIVER TRANSPLANTATION.		03.4811
Breathlessness
[description not available]		07.69135
Cough
A sudden, audible expulsion of air from the lungs through a partially closed glottis, preceded by inhalation. It is a protective response that serves to clear the trachea, bronchi, and/or lungs of irritants and secretions, or to prevent aspiration of foreign materials into the lungs.		05.0631
Dyspnea
Difficult or labored breathing.		07.69135
Convulsive Generalized Seizure Disorder
[description not available]		02.4620
Foreign Bodies
Inanimate objects that become enclosed in the body.		02.1110
Pneumothorax, Primary Spontaneous
[description not available]		03.9240
Pneumothorax
An accumulation of air or gas in the PLEURAL CAVITY, which may occur spontaneously or as a result of trauma or a pathological process. The gas may also be introduced deliberately during PNEUMOTHORAX, ARTIFICIAL.		08.9240
Choroid Plexus Papilloma
[description not available]		05.0331
Kaposi Disease
[description not available]		02.4220
Xeroderma Pigmentosum
A rare, pigmentary, and atrophic autosomal recessive disease. It is manifested as an extreme photosensitivity to ULTRAVIOLET RAYS as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA.		02.4220
Anterior Choroidal Artery Infarction
[description not available]		03.3820
Cerebral Infarction
The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction).		03.3820
Krukenberg Carcinoma
[description not available]		02.110
Labor, Premature
[description not available]		02.110
Atypical Ductal Hyperplasia
[description not available]		03.6730
Carcinoma, Intraductal, Noninfiltrating
A noninvasive (noninfiltrating) carcinoma of the breast characterized by a proliferation of malignant epithelial cells confined to the mammary ducts or lobules, without light-microscopy evidence of invasion through the basement membrane into the surrounding stroma.		03.6730
Protein Aggregation, Pathological
A biochemical phenomenon in which misfolded proteins aggregate either intra- or extracellularly. Triggered by factors such as MUTATION; POST-TRANSLATIONAL MODIFICATIONS, and environmental stress, it is generally associated with ALZHEIMER DISEASE; PARKINSON DISEASE; HUNTINGTON DISEASE; and TYPE 2 DIABETES MELLITUS.		02.1110
Cold Fingers, Hereditary
[description not available]		03.0410
Sclerosis, Systemic
[description not available]		03.6430
Esophageal Dysmotility
[description not available]		03.0410
Raynaud Disease
An idiopathic vascular disorder characterized by bilateral Raynaud phenomenon, the abrupt onset of digital paleness or CYANOSIS in response to cold exposure or stress.		03.0410
Scleroderma, Systemic
A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA.		03.6430
Benign Brenner Tumor
[description not available]		03.940
Atrophy, Muscle
[description not available]		02.110
Injuries, Spinal Cord
[description not available]		02.110
Asbestosis
A form of pneumoconiosis caused by inhalation of asbestos fibers which elicit potent inflammatory responses in the parenchyma of the lung. The disease is characterized by interstitial fibrosis of the lung, varying from scattered sites to extensive scarring of the alveolar interstitium.		02.110
Muscular Atrophy
Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation.		02.110
Spinal Cord Injuries
Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).		02.110
Autism
[description not available]		02.1110
Autistic Disorder
A disorder beginning in childhood. It is marked by the presence of markedly abnormal or impaired development in social interaction and communication and a markedly restricted repertoire of activity and interest. Manifestations of the disorder vary greatly depending on the developmental level and chronological age of the individual. (DSM-V)		02.1110
Peripheral Nerve Injury
[description not available]		02.1110
Peripheral Nerve Injuries
Injuries to the PERIPHERAL NERVES.		02.1110
Impairment, Light Touch Sensation
[description not available]		03.4811
Ischemia
A hypoperfusion of the BLOOD through an organ or tissue caused by a PATHOLOGIC CONSTRICTION or obstruction of its BLOOD VESSELS, or an absence of BLOOD CIRCULATION.		02.9640
Connective and Soft Tissue Neoplasms
[description not available]		02.110
Chondrosarcoma
A slowly growing malignant neoplasm derived from cartilage cells, occurring most frequently in pelvic bones or near the ends of long bones, in middle-aged and old people. Most chondrosarcomas arise de novo, but some may develop in a preexisting benign cartilaginous lesion or in patients with ENCHONDROMATOSIS. (Stedman, 25th ed)		02.4620
Empyema
Presence of pus in a hollow organ or body cavity.		02.1110
Mesothelial Neoplasms
[description not available]		02.1110
Brain Swelling
[description not available]		02.7430
Brain Edema
Increased intracellular or extracellular fluid in brain tissue. Cytotoxic brain edema (swelling due to increased intracellular fluid) is indicative of a disturbance in cell metabolism, and is commonly associated with hypoxic or ischemic injuries (see HYPOXIA, BRAIN). An increase in extracellular fluid may be caused by increased brain capillary permeability (vasogenic edema), an osmotic gradient, local blockages in interstitial fluid pathways, or by obstruction of CSF flow (e.g., obstructive HYDROCEPHALUS). (From Childs Nerv Syst 1992 Sep; 8(6):301-6)		02.7430
Hyperammonemia
Elevated level of AMMONIA in the blood. It is a sign of defective CATABOLISM of AMINO ACIDS or ammonia to UREA.		02.1110
Dementia Praecox
[description not available]		02.4820
Schizophrenia
A severe emotional disorder of psychotic depth characteristically marked by a retreat from reality with delusion formation, HALLUCINATIONS, emotional disharmony, and regressive behavior.		02.4820
Carcinoid Heart Disease
Cardiac manifestation of gastrointestinal CARCINOID TUMOR that metastasizes to the liver. Substances secreted by the tumor cells, including SEROTONIN, promote fibrous plaque formation in ENDOCARDIUM and its underlying layers. These deposits cause distortion of the TRICUSPID VALVE and the PULMONARY VALVE eventually leading to STENOSIS and valve regurgitation.		03.9410
Choroid Plexus Neoplasms, Primary
[description not available]		07.98131
Choroid Plexus Neoplasms
Benign or malignant tumors which arise from the choroid plexus of the ventricles of the brain. Papillomas (see PAPILLOMA, CHOROID PLEXUS) and carcinomas are the most common histologic subtypes, and tend to seed throughout the ventricular and subarachnoid spaces. Clinical features include headaches, ataxia and alterations of consciousness, primarily resulting from associated HYDROCEPHALUS. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2072; J Neurosurg 1998 Mar;88(3):521-8)		07.98131
Benign Supratentorial Neoplasms
[description not available]		07.3295
Air Embolism
[description not available]		02.110
Cancer of Paranasal Sinus
[description not available]		04.6960
Paranasal Sinus Neoplasms
Tumors or cancer of the PARANASAL SINUSES.		04.6960
Hormone-Dependent Neoplasms
[description not available]		010.872313
Multiple Neurofibromas
[description not available]		02.5220
Neurofibromatoses
A group of disorders characterized by an autosomal dominant pattern of inheritance with high rates of spontaneous mutation and multiple neurofibromas or neurilemmomas. NEUROFIBROMATOSIS 1 (generalized neurofibromatosis) accounts for approximately 95% of cases, although multiple additional subtypes (e.g., NEUROFIBROMATOSIS 2, neurofibromatosis 3, etc.) have been described. (From Neurochirurgie 1998 Nov;44(4):267-72)		02.5220
Metaplasia
A condition in which there is a change of one adult cell type to another similar adult cell type.		03.6630
Anastomotic Leak
Breakdown of the connection and subsequent leakage of effluent (fluids, secretions, air) from a SURGICAL ANASTOMOSIS of the digestive, respiratory, genitourinary, and cardiovascular systems. Most common leakages are from the breakdown of suture lines in gastrointestinal or bowel anastomosis.		02.1110
Anuria
Absence of urine formation. It is usually associated with complete bilateral ureteral (URETER) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present.		03.0310
Hematochezia
The passage of bright red blood from the rectum. The blood may or may not be mixed with formed stool in the form of blood, blood clots, bloody stool or diarrhea.		02.4920
Primary Peritonitis
[description not available]		03.2460
Gastrointestinal Hemorrhage
Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM.		02.4920
Peritonitis
INFLAMMATION of the PERITONEUM lining the ABDOMINAL CAVITY as the result of infectious, autoimmune, or chemical processes. Primary peritonitis is due to infection of the PERITONEAL CAVITY via hematogenous or lymphatic spread and without intra-abdominal source. Secondary peritonitis arises from the ABDOMINAL CAVITY itself through RUPTURE or ABSCESS of intra-abdominal organs.		03.2460
Abortion, Missed
The retention in the UTERUS of a dead FETUS two months or more after its DEATH.		02.1110
Neoplasms, Sweat Gland
[description not available]		03.6430
Acute Hepatic Failure
[description not available]		02.4820
Liver Failure, Acute
A form of rapid-onset LIVER FAILURE, also known as fulminant hepatic failure, caused by severe liver injury or massive loss of HEPATOCYTES. It is characterized by sudden development of liver dysfunction and JAUNDICE. Acute liver failure may progress to exhibit cerebral dysfunction even HEPATIC COMA depending on the etiology that includes hepatic ISCHEMIA, drug toxicity, malignant infiltration, and viral hepatitis such as post-transfusion HEPATITIS B and HEPATITIS C.		02.4820
Hypokalemia
Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed)		04.1431
Infections, Listeria
[description not available]		02.1110
Calcification, Pathologic
[description not available]		03.1450
Calcinosis
Pathologic deposition of calcium salts in tissues.		03.1450
Auricular Cancer
[description not available]		02.1310
Ear Neoplasms
Tumors or cancer of any part of the hearing and equilibrium system of the body (the EXTERNAL EAR, the MIDDLE EAR, and the INNER EAR).		02.1310
Ileus
A condition caused by the lack of intestinal PERISTALSIS or INTESTINAL MOTILITY without any mechanical obstruction. This interference of the flow of INTESTINAL CONTENTS often leads to INTESTINAL OBSTRUCTION. Ileus may be classified into postoperative, inflammatory, metabolic, neurogenic, and drug-induced.		05.0631
Failure to Thrive
A condition of substandard growth or diminished capacity to maintain normal function.		02.7130
Dysesthesia
[description not available]		05.7842
Dermatitis, Radiation-Induced
[description not available]		06.41114
Radiodermatitis
A cutaneous inflammatory reaction occurring as a result of exposure to ionizing radiation.		06.41114
Benign Clear Cell Adenofibroma
[description not available]		03.0310
Brain Hemorrhage
[description not available]		02.5320
Cavernous Angioma, Central Nervous System
[description not available]		02.1310
Anhidrotic Ectodermal Dysplasia
[description not available]		02.1310
Intracranial Hemorrhages
Bleeding within the SKULL, including hemorrhages in the brain and the three membranes of MENINGES. The escape of blood often leads to the formation of HEMATOMA in the cranial epidural, subdural, and subarachnoid spaces.		02.5320
Hemangioma, Cavernous, Central Nervous System
A vascular anomaly composed of a collection of large, thin walled tortuous VEINS that can occur in any part of the central nervous system but lack intervening nervous tissue. Familial occurrence is common and has been associated with a number of genes mapped to 7q, 7p and 3q. Clinical features include SEIZURES; HEADACHE; STROKE; and progressive neurological deficit.		02.1310
Cacosmia
[description not available]		02.520
Emaciation
Clinical manifestation of excessive LEANNESS usually caused by disease or a lack of nutrition (MALNUTRITION).		02.4420
Myxosarcoma
A sarcoma, usually a liposarcoma or malignant fibrous histiocytoma, with an abundant component of myxoid tissue resembling primitive mesenchyme containing connective tissue mucin. (Stedman, 25th ed)		02.1110
Adenocarcinoma, Alveolar
[description not available]		010.992316
Adenocarcinoma, Bronchiolo-Alveolar
A carcinoma derived from epithelium of terminal bronchioles, in which the neoplastic tissue extends along the alveolar walls and grows in small masses within the alveoli. Involvement may be uniformly diffuse and massive, or nodular, or lobular. The neoplastic cells are cuboidal or columnar and form papillary structures. Mucin may be demonstrated in some of the cells and in the material in the alveoli, which also includes denuded cells. Metastases in regional lymph nodes, and in even more distant sites, are known to occur, but are infrequent. (From Stedman, 25th ed)		010.992316
Acquired Metabolic Diseases, Brain
[description not available]		03.511
MODS
[description not available]		05.0652
Multiple Organ Failure
A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative.		05.0652
Facial Neoplasms
New abnormal growth of tissue in the FACE.		05.2741
Cardiovascular Stroke
[description not available]		02.9640
Myocardial Infarction
NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).		02.9640
Acoustic Trauma
Usually refer to hearing loss due to a single noise event such as an explosion or shotgun blast.		05.160
Hearing Loss, Noise-Induced
Hearing loss due to exposure to explosive loud noise or chronic exposure to sound level greater than 85 dB. The hearing loss is often in the frequency range 4000-6000 hertz.		05.160
Pain, Procedural
Pain associated with examination, treatment or procedures.		03.5111
Anal Gland Neoplasms
Tumors or cancer of the anal gland.		02.4920
Desmoplastic Small Cell Tumor
[description not available]		03.0310
Desmoplastic Small Round Cell Tumor
A rare, aggressive soft tissue sarcoma that primarily affects adolescents and young adults. It is most commonly found in the abdomen.		03.0310
Infective Endocarditis
[description not available]		03.0410
Endocarditis
Inflammation of the inner lining of the heart (ENDOCARDIUM), the continuous membrane lining the four chambers and HEART VALVES. It is often caused by microorganisms including bacteria, viruses, fungi, and rickettsiae. Left untreated, endocarditis can damage heart valves and become life-threatening.		03.0410
Heavy Menstrual Bleeding
[description not available]		02.1310
Menorrhagia
Excessive uterine bleeding during MENSTRUATION.		02.1310
Adenomyosis
The extension of endometrial tissue (ENDOMETRIUM) into the MYOMETRIUM. It usually occurs in women in their reproductive years and may result in a diffusely enlarged uterus with ectopic and benign endometrial glands and stroma.		02.1310
Hyperkinetic Dysphonia
[description not available]		02.1110
Dysphonia
Difficulty and/or pain in PHONATION or speaking.		02.1110
Remission, Spontaneous
A spontaneous diminution or abatement of a disease over time, without formal treatment.		02.7130
Autoimmune Thrombocytopenia
[description not available]		03.3420
Purpura, Thrombocytopenic, Idiopathic
Thrombocytopenia occurring in the absence of toxic exposure or a disease associated with decreased platelets. It is mediated by immune mechanisms, in most cases IMMUNOGLOBULIN G autoantibodies which attach to platelets and subsequently undergo destruction by macrophages. The disease is seen in acute (affecting children) and chronic (adult) forms.		03.3420
Aesthesioneuroblastoma
[description not available]		04.6561
Esthesioneuroblastoma, Olfactory
A malignant olfactory neuroblastoma arising from the olfactory epithelium of the superior nasal cavity and cribriform plate. It is uncommon (3% of nasal tumors) and rarely is associated with the production of excess hormones (e.g., SIADH, Cushing Syndrome). It has a high propensity for multiple local recurrences and bony metastases. (From Holland et al., Cancer Medicine, 3rd ed, p1245; J Laryngol Otol 1998 Jul;112(7):628-33)		04.6561
Glaucoma
An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. (Dictionary of Visual Science, 4th ed)		02.1310
Cirrhosis
[description not available]		05.8283
Fibrosis
Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.		010.8283
Dermatitis, Eczematous
[description not available]		02.5320
Eczema
A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed).		02.5320
Dyslipidemia
[description not available]		03.0410
Adnexal Diseases
Diseases of the uterine appendages (ADNEXA UTERI) including diseases involving the OVARY, the FALLOPIAN TUBES, and ligaments of the uterus (BROAD LIGAMENT; ROUND LIGAMENT).		03.4120
Cystadenocarcinoma
A malignant neoplasm derived from glandular epithelium, in which cystic accumulations of retained secretions are formed. The neoplastic cells manifest varying degrees of anaplasia and invasiveness, and local extension and metastases occur. Cystadenocarcinomas develop frequently in the ovaries, where pseudomucinous and serous types are recognized. (Stedman, 25th ed)		07.8232
Dyslipidemias
Abnormalities in the serum levels of LIPIDS, including overproduction or deficiency. Abnormal serum lipid profiles may include high total CHOLESTEROL, high TRIGLYCERIDES, low HIGH DENSITY LIPOPROTEIN CHOLESTEROL, and elevated LOW DENSITY LIPOPROTEIN CHOLESTEROL.		03.0410
Pulmonary Hypertension
[description not available]		02.520
Hepatic Veno Occlusive Disease
[description not available]		06.0461
Hepatic Veno-Occlusive Disease
Liver disease that is caused by injuries to the ENDOTHELIAL CELLS of the vessels and subendothelial EDEMA, but not by THROMBOSIS. Extracellular matrix, rich in FIBRONECTINS, is usually deposited around the HEPATIC VEINS leading to venous outflow occlusion and sinusoidal obstruction.		06.0461
Hypertension, Pulmonary
Increased VASCULAR RESISTANCE in the PULMONARY CIRCULATION, usually secondary to HEART DISEASES or LUNG DISEASES.		02.520
Acute Edematous Pancreatitis
[description not available]		03.1650
Pancreatitis
INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis.		03.1650
Lymphangitis
A lymphatic disease characterized by INFLAMMATION of LYMPHATIC VESSELS.		02.4220
Body Dysmorphic Disorders
Preoccupations with appearance or self-image causing significant distress or impairment in important areas of functioning.		02.1310
Equine Diseases
[description not available]		02.1510
Hemoperitoneum
Accumulations of blood in the PERITONEAL CAVITY due to internal HEMORRHAGE.		02.1510
Hepatitis, Viral, Non-A, Non-B, Parenterally-Transmitted
[description not available]		03.5111
Hepatitis C
INFLAMMATION of the LIVER in humans caused by HEPATITIS C VIRUS, a single-stranded RNA virus. Its incubation period is 30-90 days. Hepatitis C is transmitted primarily by contaminated blood parenterally and is often associated with transfusion and intravenous drug abuse. However, in a significant number of cases, the source of hepatitis C infection is unknown.		03.5111
Child Mental Disorders
[description not available]		02.1310
Neurodevelopmental Disorders
These are a group of conditions with onset in the developmental period. The disorders typically manifest early in development, often before the child enters grade school, and are characterized by developmental deficits that produce impairments of personal, social, academic, or occupational functioning. (From DSM-5).		02.1310
Leanness
[description not available]		03.8621
Choriocarcinoma, Non-gestational
A highly malignant CHORIOCARCINOMA derived from the non-placental origin such as the totipotent cells in the TESTIS, the OVARY, and the PINEAL GLAND. It produces high levels of CHORIONIC GONADOTROPIN and can metastasize widely through the bloodstream to the lungs, brain, liver, bone, and other viscera by the time of diagnosis.		02.4720
Basal Ganglia Diseases
Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.		03.3720
Brachial Paresis
[description not available]		03.6630
Absence Seizure
[description not available]		05.7171
Seizures
Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as EPILEPSY or seizure disorder.		05.7171
Carcinoma, Embryonal
A highly malignant, primitive form of carcinoma, probably of germinal cell or teratomatous derivation, usually arising in a gonad and rarely in other sites. It is rare in the female ovary, but in the male it accounts for 20% of all testicular tumors. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, p1595)		04.370
Leiomyosarcoma, Epithelioid
[description not available]		05.3472
Leiomyosarcoma
A sarcoma containing large spindle cells of smooth muscle. Although it rarely occurs in soft tissue, it is common in the viscera. It is the most common soft tissue sarcoma of the gastrointestinal tract and uterus. The median age of patients is 60 years. (From Dorland, 27th ed; Holland et al., Cancer Medicine, 3d ed, p1865)		05.3472
ANS (Autonomic Nervous System) Diseases
[description not available]		02.1310
Central Nervous System Origin Vertigo
[description not available]		02.1310
Vertigo
An illusion of movement, either of the external world revolving around the individual or of the individual revolving in space. Vertigo may be associated with disorders of the inner ear (EAR, INNER); VESTIBULAR NERVE; BRAINSTEM; or CEREBRAL CORTEX. Lesions in the TEMPORAL LOBE and PARIETAL LOBE may be associated with FOCAL SEIZURES that may feature vertigo as an ictal manifestation. (From Adams et al., Principles of Neurology, 6th ed, pp300-1)		02.1310
Chromosomal Instability
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.		02.1510
Chromosome-Defective Micronuclei
[description not available]		02.7230
Cystadenoma, Serous
A cystic tumor of the ovary, containing thin, clear, yellow serous fluid and varying amounts of solid tissue, with a malignant potential several times greater than that of mucinous cystadenoma (CYSTADENOMA, MUCINOUS). It can be unilocular, parvilocular, or multilocular. It is often bilateral and papillary. The cysts may vary greatly in size. (Dorland, 27th ed; from Hughes, Obstetric-Gynecologic Terminology, 1972)		03.6530
Anemia, Macrocytic
Anemia characterized by larger than normal erythrocytes, increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).		03.0610
Abnormalities, Autosome
[description not available]		05.41140
Chromosome Deletion
Actual loss of portion of a chromosome.		04.0450
Femoral Neoplasms
New abnormal growth of tissue in the FEMUR.		04.0150
Urinary Tract Infections
Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA.		02.1510
Femoral Fractures
Fractures of the femur.		02.1510
Abdomen, Acute
A clinical syndrome with acute abdominal pain that is severe, localized, and rapid in onset. Acute abdomen may be caused by a variety of disorders, injuries, or diseases.		02.520
Mast-Cell Leukemia
[description not available]		02.1510
Leukemia, Mast-Cell
A form of systemic mastocytosis (MASTOCYTOSIS, SYSTEMIC) characterized by the presence of large numbers of tissue MAST CELLS in the peripheral blood without skin lesions. It is a high-grade LEUKEMIA disease with bone marrow smear of		02.1510
Nociceptive Pain
Dull or sharp aching pain caused by stimulated NOCICEPTORS due to tissue injury, inflammation or diseases. It can be divided into somatic or tissue pain and VISCERAL PAIN.		02.1510
Anhedonia
Inability to experience pleasure due to impairment or dysfunction of normal psychological and neurobiological mechanisms. It is a symptom of many PSYCHOTIC DISORDERS (e.g., DEPRESSIVE DISORDER, MAJOR; and SCHIZOPHRENIA).		02.1510
Depression
Depressive states usually of moderate intensity in contrast with MAJOR DEPRESSIVE DISORDER present in neurotic and psychotic disorders.		04.1231
Appetite Disorders
[description not available]		02.1510
Feeding and Eating Disorders
A group of disorders characterized by physiological and psychological disturbances in appetite or food intake.		02.1510
Distorted Hearing
[description not available]		03.79110
Cutaneous T-Cell Lymphoma
[description not available]		02.0410
Lymphoma, T-Cell, Cutaneous
A group of lymphomas exhibiting clonal expansion of malignant T-lymphocytes arrested at varying stages of differentiation as well as malignant infiltration of the skin. MYCOSIS FUNGOIDES; SEZARY SYNDROME; LYMPHOMATOID PAPULOSIS; and PRIMARY CUTANEOUS ANAPLASTIC LARGE CELL LYMPHOMA are the best characterized of these disorders.		02.0410
Dermatomyositis, Adult Type
[description not available]		02.4220
Leg Dermatoses
A nonspecific term used to denote any cutaneous lesion or group of lesions, or eruptions of any type on the leg. (From Stedman, 25th ed)		02.0410
Dermatomyositis
A subacute or chronic inflammatory disease of muscle and skin, marked by proximal muscle weakness and a characteristic skin rash. The illness occurs with approximately equal frequency in children and adults. The skin lesions usually take the form of a purplish rash (or less often an exfoliative dermatitis) involving the nose, cheeks, forehead, upper trunk, and arms. The disease is associated with a complement mediated intramuscular microangiopathy, leading to loss of capillaries, muscle ischemia, muscle-fiber necrosis, and perifascicular atrophy. The childhood form of this disease tends to evolve into a systemic vasculitis. Dermatomyositis may occur in association with malignant neoplasms. (From Adams et al., Principles of Neurology, 6th ed, pp1405-6)		02.4220
Venous Insufficiency
Impaired venous blood flow or venous return (venous stasis), usually caused by inadequate venous valves. Venous insufficiency often occurs in the legs, and is associated with EDEMA and sometimes with VENOUS STASIS ULCERS at the ankle.		02.0410
Back Ache
[description not available]		02.4420
Back Pain
Acute or chronic pain located in the posterior regions of the THORAX; LUMBOSACRAL REGION; or the adjacent regions.		02.4420
Spinal Neoplasms
New abnormal growth of tissue in the SPINE.		04.88130
Adult Premature Aging Syndrome
[description not available]		02.0510
Sarcoma 180
An experimental sarcoma of mice.		03.2560
Adhesions, Tissue
[description not available]		04.341
Peritoneal Diseases
Pathological processes involving the PERITONEUM.		03.8121
Endometrial Diseases
[description not available]		02.0410
Uterine Diseases
Pathological processes involving any part of the UTERUS.		02.0410
Condition, Preneoplastic
[description not available]		05.0331
Gynandroblastoma
A sex cord-gonadal stromal tumor, composed of cells of both the OVARY and the TESTIS. It produces both male and female GONADAL STEROID HORMONES.		03.4311
Precancerous Conditions
Pathological conditions that tend eventually to become malignant.		05.0331
Sex Cord-Gonadal Stromal Tumors
Neoplasms derived from the primitive sex cord or gonadal stromal cells of the embryonic GONADS. They are classified by their presumed histogenesis and differentiation. From the sex cord, there are SERTOLI CELL TUMOR and GRANULOSA CELL TUMOR; from the gonadal stroma, LEYDIG CELL TUMOR and THECOMA. These tumors may be identified in either the OVARY or the TESTIS.		03.4311
Diabetic Glomerulosclerosis
[description not available]		02.0410
Diabetic Nephropathies
KIDNEY injuries associated with diabetes mellitus and affecting KIDNEY GLOMERULUS; ARTERIOLES; KIDNEY TUBULES; and the interstitium. Clinical signs include persistent PROTEINURIA, from microalbuminuria progressing to ALBUMINURIA of greater than 300 mg/24 h, leading to reduced GLOMERULAR FILTRATION RATE and END-STAGE RENAL DISEASE.		02.0410
Esophagotracheal Fistula
[description not available]		02.7430
Froehlich's Syndrome
[description not available]		02.0410
Hemangioendothelioma, Epithelioid
A tumor of medium-to-large veins, composed of plump-to-spindled endothelial cells that bulge into vascular spaces in a tombstone-like fashion. These tumors are thought to have borderline aggression, where one-third develop local recurrences, but only rarely metastasize. It is unclear whether the epithelioid hemangioendothelioma is truly neoplastic or an exuberant tissue reaction, nor is it clear if this is equivalent to Kimura's disease (see ANGIOLYMPHOID HYPERPLASIA WITH EOSINOPHILIA). (Segen, Dictionary of Modern Medicine, 1992)		02.4220
B-Cell Leukemia
[description not available]		04.3511
Ectropion
The turning outward (eversion) of the edge of the eyelid, resulting in the exposure of the palpebral conjunctiva. (Dorland, 27th ed)		02.0410
Joint Pain
[description not available]		06.96127
Arthralgia
Pain in the joint.		06.96127
Abnormalities, Drug-Induced
Congenital abnormalities caused by medicinal substances or drugs of abuse given to or taken by the mother, or to which she is inadvertently exposed during the manufacture of such substances. The concept excludes abnormalities resulting from exposure to non-medicinal chemicals in the environment.		03.6130
Altidudinal Hemianopia
[description not available]		02.9610
Signet Ring Cell Carcinoma
[description not available]		05.4351
Carcinoma, Signet Ring Cell
A poorly differentiated adenocarcinoma in which the nucleus is pressed to one side by a cytoplasmic droplet of mucus. It usually arises in the gastrointestinal system.		05.4351
Submandibular Gland Neoplasms
New abnormal growth of tissue in the SUBMANDIBULAR GLAND.		02.0510
Focal Nodular Hyperplasia
Solitary or multiple benign hepatic vascular tumors, usually occurring in women of 20-50 years of age. The nodule, poorly encapsulated, consists of a central stellate fibrous scar and normal liver elements such as HEPATOCYTES, small BILE DUCTS, and KUPFFER CELLS among the intervening fibrous septa. The pale colored central scar represents large blood vessels with hyperplastic fibromuscular layer and narrowing lumen.		02.0410
Polyuria
Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes (DIABETES MELLITUS; DIABETES INSIPIDUS).		02.0410
Keratoacanthoma
A benign, non-neoplastic, usually self-limiting epithelial lesion closely resembling squamous cell carcinoma clinically and histopathologically. It occurs in solitary, multiple, and eruptive forms. The solitary and multiple forms occur on sunlight exposed areas and are identical histologically; they affect primarily white males. The eruptive form usually involves both sexes and appears as a generalized papular eruption.		02.0510
Hypertriglyceridemia
A condition of elevated levels of TRIGLYCERIDES in the blood.		04.6732
Neoplasms, Vascular
[description not available]		03.1550
Absence Status
[description not available]		02.4320
Status Epilepticus
A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition (see also EPILEPSIA PARTIALIS CONTINUA). Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. (From N Engl J Med 1998 Apr 2;338(14):970-6; Neurologia 1997 Dec;12 Suppl 6:25-30)		02.4320
Diplopia
A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include REFRACTIVE ERRORS; STRABISMUS; OCULOMOTOR NERVE DISEASES; TROCHLEAR NERVE DISEASES; ABDUCENS NERVE DISEASES; and diseases of the BRAIN STEM and OCCIPITAL LOBE.		02.7430
Central Nervous System Cysts
Congenital or acquired cysts of the brain, spinal cord, or meninges which may remain stable in size or undergo progressive enlargement.		02.4420
Onycholysis
Separation of nail plate from the underlying nail bed. It can be a sign of skin disease, infection (such as ONYCHOMYCOSIS) or tissue injury.		02.0510
Glioblastoma with Sarcomatous Component
[description not available]		02.7230
Gliosarcoma
Rare mixed tumors of the brain and rarely the spinal cord which contain malignant neuroectodermal (glial) and mesenchymal components, including spindle-shaped fibrosarcoma cells. These tumors are highly aggressive and present primarily in adults as rapidly expanding mass lesions. They may arise in tissue that has been previously irradiated. (From Br J Neurosurg 1995 Apr;9(2):171-8)		02.7230
Endothelioma, Vascular
[description not available]		02.0510
Hemangioendothelioma
A neoplasm derived from blood vessels, characterized by numerous prominent endothelial cells that occur singly, in aggregates, and as the lining of congeries of vascular tubes or channels. Hemangioendotheliomas are relatively rare and are of intermediate malignancy (between benign hemangiomas and conventional angiosarcomas). They affect men and women about equally and rarely develop in childhood. (From Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1866)		02.0510
Sarcoma, Small Cell
A sarcoma characterized by the presence of small cells, cells measuring 9-14 micrometers with a faint or indistinct rim of cytoplasm and an oval-to-elongated nucleus with relatively dense chromatin. (From Segen, Dictionary of Modern Medicine, 1992)		02.4320
Carcinoma, Intraepithelial
[description not available]		06.9591
Carcinoma in Situ
A lesion with cytological characteristics associated with invasive carcinoma but the tumor cells are confined to the epithelium of origin, without invasion of the basement membrane.		06.9591
Sexually Transmitted Diseases
Diseases due to or propagated by sexual contact.		02.0410
Alcohol Drinking
Behaviors associated with the ingesting of ALCOHOLIC BEVERAGES, including social drinking.		02.0510
Auditory Cortex Disorder
[description not available]		03.6430
Coin Lesion, Pulmonary
[description not available]		02.9610
Cyst
[description not available]		02.9610
Lymphatic Diseases
Diseases of LYMPH; LYMPH NODES; or LYMPHATIC VESSELS.		03.3820
Enlarged Spleen
[description not available]		02.0510
Adult-Onset Still Disease
[description not available]		02.0510
Still's Disease, Adult-Onset
Systemic-onset rheumatoid arthritis in adults. It differs from classical rheumatoid arthritis in that it is more often marked by acute febrile onset, and generalized lymphadenopathy and hepatosplenomegaly are more prominent.		02.0510
Brain Damage, Chronic
A condition characterized by long-standing brain dysfunction or damage, usually of three months duration or longer. Potential etiologies include BRAIN INFARCTION; certain NEURODEGENERATIVE DISORDERS; CRANIOCEREBRAL TRAUMA; ANOXIA, BRAIN; ENCEPHALITIS; certain NEUROTOXICITY SYNDROMES; metabolic disorders (see BRAIN DISEASES, METABOLIC); and other conditions.		04.3341
Deficiency, Mental
[description not available]		02.0510
Intellectual Disability
Subnormal intellectual functioning which originates during the developmental period. This has multiple potential etiologies, including genetic defects and perinatal insults. Intelligence quotient (IQ) scores are commonly used to determine whether an individual has an intellectual disability. IQ scores between 70 and 79 are in the borderline range. Scores below 67 are in the disabled range. (from Joynt, Clinical Neurology, 1992, Ch55, p28)		02.0510
Aspergilloses, Bronchopulmonary
[description not available]		02.0510
Pulmonary Aspergillosis
Infections of the respiratory tract with fungi of the genus ASPERGILLUS.		02.0510
Cranial Nerve V Diseases
[description not available]		02.0510
Benign Cranial Nerve Neoplasms
[description not available]		04.4851
Chordoma
A malignant tumor arising from the embryonic remains of the notochord. It is also called chordocarcinoma, chordoepithelioma, and notochordoma. (Dorland, 27th ed)		07.4620
Elevated Cholesterol
[description not available]		02.0510
Hypercholesterolemia
A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.		02.0510
Leukemia, Myelogenous, Aggressive Phase
[description not available]		03.4411
Blast Phase
[description not available]		07.3586
Blast Crisis
An advanced phase of chronic myelogenous leukemia, characterized by a rapid increase in the proportion of immature white blood cells (blasts) in the blood and bone marrow to greater than 30%.		07.3586
Aneuploid
[description not available]		03.6230
Ataxia Telangiectasia Syndrome
[description not available]		03.3620
Ataxia Telangiectasia
An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).		03.3620
Acneiform Eruptions
Visible efflorescent lesions of the skin caused by acne or resembling acne. (Dorland, 28th ed, p18, 575)		03.4411
Flank Pain
Pain emanating from below the RIBS and above the ILIUM.		02.0510
Cyclitis, Chronic
[description not available]		02.0510
Uveitis, Intermediate
Inflammation of the pars plana, ciliary body, and adjacent structures.		02.0510
Drug-Induced Stevens Johnson Syndrome
[description not available]		03.3520
Stevens-Johnson Syndrome
Rare cutaneous eruption characterized by extensive KERATINOCYTE apoptosis resulting in skin detachment with mucosal involvement. It is often provoked by the use of drugs (e.g., antibiotics and anticonvulsants) or associated with PNEUMONIA, MYCOPLASMA. It is considered a continuum of Toxic Epidermal Necrolysis.		03.3520
Klein Syndrome
[description not available]		02.0510
Gangliocytoma
[description not available]		02.4320
Aqueductal Stenosis
[description not available]		03.8540
Mixed Pineocytoma-Pineoblastoma
[description not available]		03.88120
Pinealoma
Neoplasms which originate from pineal parenchymal cells that tend to enlarge the gland and be locally invasive. The two major forms are pineocytoma and the more malignant pineoblastoma. Pineocytomas have moderate cellularity and tend to form rosette patterns. Pineoblastomas are highly cellular tumors containing small, poorly differentiated cells. These tumors occasionally seed the neuroaxis or cause obstructive HYDROCEPHALUS or Parinaud's syndrome. GERMINOMA; CARCINOMA, EMBRYONAL; GLIOMA; and other neoplasms may arise in the pineal region with germinoma being the most common pineal region tumor. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2064; Adams et al., Principles of Neurology, 6th ed, p670)		03.88120
Cystadenoma
A benign neoplasm derived from glandular epithelium, in which cystic accumulations of retained secretions are formed. In some instances, considerable portions of the neoplasm, or even the entire mass, may be cystic. (Stedman, 25th ed)		02.0510
Antibiotic-Associated Colitis
[description not available]		02.7130
Enterocolitis, Pseudomembranous
An acute inflammation of the INTESTINAL MUCOSA that is characterized by the presence of pseudomembranes or plaques in the SMALL INTESTINE (pseudomembranous enteritis) and the LARGE INTESTINE (pseudomembranous colitis). It is commonly associated with antibiotic therapy and CLOSTRIDIUM DIFFICILE colonization.		02.7130
Sinus Infections
[description not available]		02.0510
Sinusitis
Inflammation of the NASAL MUCOSA in one or more of the PARANASAL SINUSES.		02.0510
Hospital-Acquired Condition
[description not available]		02.0510
Follicular Thyroid Carcinoma
[description not available]		02.4620
Adenocarcinoma, Follicular
An adenocarcinoma of the thyroid gland, in which the cells are arranged in the form of follicles. (From Dorland, 27th ed)		02.4620
Delayed Puberty
[description not available]		02.0510
Adenohypophyseal Diseases
[description not available]		02.4120
Pituitary Diseases
Disorders involving either the ADENOHYPOPHYSIS or the NEUROHYPOPHYSIS. These diseases usually manifest as hypersecretion or hyposecretion of PITUITARY HORMONES. Neoplastic pituitary masses can also cause compression of the OPTIC CHIASM and other adjacent structures.		02.4120
Erythroderma, Sezary
[description not available]		02.0510
Sezary Syndrome
A form of cutaneous T-cell lymphoma manifested by generalized exfoliative ERYTHRODERMA; PRURITUS; peripheral lymphadenopathy, and abnormal hyperchromatic mononuclear (cerebriform) cells in the skin, LYMPH NODES, and peripheral blood (Sezary cells).		02.0510
Adenitis
[description not available]		02.0510
Kawasaki Disease
[description not available]		02.0510
Bartonella henselae Infection
[description not available]		02.0510
Cat-Scratch Disease
A self-limiting bacterial infection of the regional lymph nodes caused by AFIPIA felis, a gram-negative bacterium recently identified by the Centers for Disease Control and Prevention and by BARTONELLA HENSELAE. It usually arises one or more weeks following a feline scratch, with raised inflammatory nodules at the site of the scratch being the primary symptom.		02.0510
Mucocutaneous Lymph Node Syndrome
An acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes in infants and young children. The principal symptoms are fever, congestion of the ocular conjunctivae, reddening of the lips and oral cavity, protuberance of tongue papillae, and edema or erythema of the extremities.		02.0510
Cancer of Jejunum
[description not available]		02.4120
Dancing Eyes-Dancing Feet Syndrome
[description not available]		02.0610
Opsoclonus-Myoclonus Syndrome
A neurological condition that is characterized by uncontrolled rapid irregular movements of the eye (OPSOCLONUS) and the muscle (MYOCLONUS) causing unsteady, trembling gait. It is also known as dancing eyes-dancing feet syndrome and is often associated with neoplasms, viral infections, or autoimmune disorders involving the nervous system.		02.0610
Hearing Loss, High-Frequency
Hearing loss in frequencies above 1000 hertz.		04.5190
Gasser Syndrome
[description not available]		04.6460
Hemolytic-Uremic Syndrome
A syndrome that is associated with microvascular diseases of the KIDNEY, such as RENAL CORTICAL NECROSIS. It is characterized by hemolytic anemia (ANEMIA, HEMOLYTIC); THROMBOCYTOPENIA; and ACUTE RENAL FAILURE.		04.6460
Choriocarcinoma
A malignant metastatic form of trophoblastic tumors. Unlike the HYDATIDIFORM MOLE, choriocarcinoma contains no CHORIONIC VILLI but rather sheets of undifferentiated cytotrophoblasts and syncytiotrophoblasts (TROPHOBLASTS). It is characterized by the large amounts of CHORIONIC GONADOTROPIN produced. Tissue origins can be determined by DNA analyses: placental (fetal) origin or non-placental origin (CHORIOCARCINOMA, NON-GESTATIONAL).		05.26121
Cognition Disorders
Disorders characterized by disturbances in mental processes related to learning, thinking, reasoning, and judgment.		05.9952
Diverticulum, Meckel
[description not available]		02.0510
Malignant Fibrohistiocytic Tumors
[description not available]		03.4411
Histiocytoma, Malignant Fibrous
The most commonly diagnosed soft tissue sarcoma. It is a neoplasm with a fibrohistiocytic appearance found chiefly in later adult life, with peak incidence in the 7th decade.		03.4411
Dermatosclerosis
[description not available]		02.0510
Scleroderma, Localized
A term used to describe a variety of localized asymmetrical SKIN thickening that is similar to those of SYSTEMIC SCLERODERMA but without the disease features in the multiple internal organs and BLOOD VESSELS. Lesions may be characterized as patches or plaques (morphea), bands (linear), or nodules.		02.0510
Cadaver
A dead body, usually a human body.		04.1231
Bright Disease
A historical classification which is no longer used. It described acute glomerulonephritis, acute nephritic syndrome, or acute nephritis. Named for Richard Bright.		02.4320
Glomerulonephritis
Inflammation of the renal glomeruli (KIDNEY GLOMERULUS) that can be classified by the type of glomerular injuries including antibody deposition, complement activation, cellular proliferation, and glomerulosclerosis. These structural and functional abnormalities usually lead to HEMATURIA; PROTEINURIA; HYPERTENSION; and RENAL INSUFFICIENCY.		02.4320
Carcinoma, Lewis Lung
A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.		03.5180
Cataract, Membranous
[description not available]		02.4620
Cataract
Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). (Dorland, 27th ed)		02.4620
Bacterial Disease
[description not available]		05.262
Bacterial Infections
Infections by bacteria, general or unspecified.		05.262
Pulmonary Sarcoidosis
[description not available]		02.0510
Sarcoidosis, Pulmonary
Sarcoidosis affecting predominantly the lungs, the site most frequently involved and most commonly causing morbidity and mortality in sarcoidosis. Pulmonary sarcoidosis is characterized by sharply circumscribed granulomas in the alveolar, bronchial, and vascular walls, composed of tightly packed cells derived from the mononuclear phagocyte system. The clinical symptoms when present are dyspnea upon exertion, nonproductive cough, and wheezing. (Cecil Textbook of Medicine, 19th ed, p431)		02.0510
Infection, Mycobacterium avium-intracellulare
[description not available]		02.0510
Mycobacterium avium-intracellulare Infection
A nontuberculous infection when occurring in humans. It is characterized by pulmonary disease, lymphadenitis in children, and systemic disease in AIDS patients. Mycobacterium avium-intracellulare infection of birds and swine results in tuberculosis.		02.0510
Sclerosis
A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve.		02.0510
Vesico-Vaginal Fistula
[description not available]		03.4511
Sickle Cell Trait
The condition of being heterozygous for hemoglobin S.		02.4720
Acinar Carcinoma
[description not available]		02.7630
Carcinoma, Acinar Cell
A malignant tumor arising from secreting cells of a racemose gland, particularly the salivary glands. Racemose (Latin racemosus, full of clusters) refers, as does acinar (Latin acinus, grape), to small saclike dilatations in various glands. Acinar cell carcinomas are usually well differentiated and account for about 13% of the cancers arising in the parotid gland. Lymph node metastasis occurs in about 16% of cases. Local recurrences and distant metastases many years after treatment are common. This tumor appears in all age groups and is most common in women. (Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1240; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575)		02.7630
Anti-Yo-Associated Paraneoplastic Cerebellar Degeneration
[description not available]		02.0610
Polyneuropathy, Acquired
[description not available]		03.8221
Polyneuropathies
Diseases of multiple peripheral nerves simultaneously. Polyneuropathies usually are characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. The pathological processes affecting peripheral nerves include degeneration of the axon, myelin or both. The various forms of polyneuropathy are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance.		03.8221
Convergent Strabismus
[description not available]		02.0510
Esotropia
A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a cross-eye appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze.		02.0510
Vascular Malformations
A spectrum of congenital, inherited, or acquired abnormalities in BLOOD VESSELS that can adversely affect the normal blood flow in ARTERIES or VEINS. Most are congenital defects such as abnormal communications between blood vessels (fistula), shunting of arterial blood directly into veins bypassing the CAPILLARIES (arteriovenous malformations), formation of large dilated blood blood-filled vessels (cavernous angioma), and swollen capillaries (capillary telangiectases). In rare cases, vascular malformations can result from trauma or diseases.		02.0610
Benign Infratentorial Neoplasms
[description not available]		03.8421
Elephantiasis Neuromatosis
[description not available]		02.0610
Neurofibroma, Plexiform
A type of neurofibroma manifesting as a diffuse overgrowth of subcutaneous tissue, usually involving the face, scalp, neck, and chest but occasionally occurring in the abdomen or pelvis. The tumors tend to progress, and may extend along nerve roots to eventually involve the spinal roots and spinal cord. This process is almost always a manifestation of NEUROFIBROMATOSIS 1. (From Adams et al., Principles of Neurology, 6th ed, p1016; J Pediatr 1997 Nov;131(5):678-82)		02.0610
Opportunistic Infections
An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression.		04.1131
Cranial Nerve IV Diseases
[description not available]		02.0610
Choked Disk
[description not available]		02.4420
Adenomatous Polyposis Coli, Familial
[description not available]		05.2241
Papilledema
Swelling of the OPTIC DISK, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause OPTIC ATROPHY and visual loss. (Miller et al., Clinical Neuro-Ophthalmology, 4th ed, p175)		02.4420
Adenomatous Polyposis Coli
A polyposis syndrome due to an autosomal dominant mutation of the APC genes (GENES, APC) on CHROMOSOME 5. The syndrome is characterized by the development of hundreds of ADENOMATOUS POLYPS in the COLON and RECTUM of affected individuals by early adulthood.		05.2241
Fracture, Pathologic
[description not available]		03.8640
Adenoma, Prostatic
[description not available]		02.9810
Prostatic Hyperplasia
Increase in constituent cells in the PROSTATE, leading to enlargement of the organ (hypertrophy) and adverse impact on the lower urinary tract function. This can be caused by increased rate of cell proliferation, reduced rate of cell death, or both.		02.9810
Ectopic ACTH Syndrome
[description not available]		02.7230
ACTH Syndrome, Ectopic
Symptom complex due to ACTH production by non-pituitary neoplasms.		02.7230
Duncan Disease
[description not available]		02.7330
Lymphoproliferative Disorders
Disorders characterized by proliferation of lymphoid tissue, general or unspecified.		02.7330
Bronze Diabetes
[description not available]		02.0610
Hemochromatosis
A disorder of iron metabolism characterized by a triad of HEMOSIDEROSIS; LIVER CIRRHOSIS; and DIABETES MELLITUS. It is caused by massive iron deposits in parenchymal cells that may develop after a prolonged increase of iron absorption. (Jablonski's Dictionary of Syndromes & Eponymic Diseases, 2d ed)		02.0610
Hydatid Cyst of Morgagni
[description not available]		02.9810
Corpus Luteum Cyst
[description not available]		02.0710
Ovarian Cysts
General term for CYSTS and cystic diseases of the OVARY.		02.0710
Bradyarrhythmia
[description not available]		02.9810
Bradycardia
Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.		07.9810
Adenofibroma
A benign neoplasm composed of glandular and fibrous tissues, with a relatively large proportion of glands. (Stedman, 25th ed)		02.0710
Mixed Tumor, Malignant
A malignant tumor composed of more than one type of neoplastic tissue. (Dorland, 27th ed)		03.8540
Dizzyness
[description not available]		03.8621
Dizziness
An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness.		03.8621
Mastitis
INFLAMMATION of the BREAST, or MAMMARY GLAND.		02.0610
Rectovaginal Fistula
An abnormal anatomical passage between the RECTUM and the VAGINA.		02.0610
Urinary Bladder Fistula
An abnormal passage in the URINARY BLADDER or between the bladder and any surrounding organ.		02.0610
Androgenization
[description not available]		02.9810
Albinism
General term for a number of inherited defects of amino acid metabolism in which there is a deficiency or absence of pigment in the eyes, skin, or hair.		02.0510
Idiopathic Parkinson Disease
[description not available]		02.7130
Psychoses
[description not available]		02.0610
Parkinson Disease
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)		02.7130
Psychotic Disorders
Disorders in which there is a loss of ego boundaries or a gross impairment in reality testing with delusions or prominent hallucinations. (From DSM-IV, 1994)		02.0610
Auricular Flutter
[description not available]		02.4620
Atrial Flutter
Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).		07.4620
Laryngeal Diseases
Pathological processes involving any part of the LARYNX which coordinates many functions such as voice production, breathing, swallowing, and coughing.		02.0710
Alveolar Echinococcosis, Hepatic
[description not available]		02.0610
Histiocytic Sarcoma
Malignant neoplasms composed of MACROPHAGES or DENDRITIC CELLS. Most histiocytic sarcomas present as localized tumor masses without a leukemic phase. Though the biological behavior of these neoplasms resemble lymphomas, their cell lineage is histiocytic not lymphoid.		02.0710
Choroid Neovascularization
[description not available]		02.0710
Neovascularization, Optic Disc
[description not available]		02.0710
Retinal Neovascularization
Formation of new blood vessels originating from the retinal veins and extending along the inner (vitreal) surface of the retina.		02.0710
Adenoma, alpha-Cell
[description not available]		02.0610
Eye Abnormalities
Congenital absence of or defects in structures of the eye; may also be hereditary.		02.0610
Afferent Pupillary Defect
[description not available]		02.0610
Eye Pain
A dull or sharp painful sensation associated with the outer or inner structures of the eyeball, having different causes.		02.0610
Anemia, Hypochromic
Anemia characterized by a decrease in the ratio of the weight of hemoglobin to the volume of the erythrocyte, i.e., the mean corpuscular hemoglobin concentration is less than normal. The individual cells contain less hemoglobin than they could have under optimal conditions. Hypochromic anemia may be caused by iron deficiency from a low iron intake, diminished iron absorption, or excessive iron loss. It can also be caused by infections or other diseases, therapeutic drugs, lead poisoning, and other conditions. (Stedman, 25th ed; from Miale, Laboratory Medicine: Hematology, 6th ed, p393)		02.0610
Chromosomal Duplication
[description not available]		02.0710
Micrometastases, Neoplasm
[description not available]		03.4611
Hypotension, Postural
[description not available]		02.0710
Hypotension, Orthostatic
A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE.		02.0710
Adrenal Gland Hyperfunction
[description not available]		02.0710
Adrenocortical Hyperfunction
Excess production of ADRENAL CORTEX HORMONES such as ALDOSTERONE; HYDROCORTISONE; DEHYDROEPIANDROSTERONE; and/or ANDROSTENEDIONE. Hyperadrenal syndromes include CUSHING SYNDROME; HYPERALDOSTERONISM; and VIRILISM.		02.0710
Rib Fractures
Fractures of any of the RIBS.		02.9910
Human T-lymphotropic Virus 1 Infection
[description not available]		02.4520
HTLV-I Infections
Diseases caused by HUMAN T-LYMPHOTROPIC VIRUS 1.		02.4520
Angina at Rest
[description not available]		02.0710
Angina, Unstable
Precordial pain at rest, which may precede a MYOCARDIAL INFARCTION.		02.0710
Abscess, Abdominal
[description not available]		03.4611
Intestinal Obstruction
Any impairment, arrest, or reversal of the normal flow of INTESTINAL CONTENTS toward the ANAL CANAL.		03.8421
Abdominal Abscess
An abscess located in the abdominal cavity, i.e., the cavity between the diaphragm above and the pelvis below. (From Dorland, 27th ed)		03.4611
Esophageal Perforation
An opening or hole in the ESOPHAGUS that is caused by TRAUMA, injury, or pathological process.		02.0710
Prosthesis Durability
[description not available]		02.0710
Luft Disease
[description not available]		02.0710
Mitochondrial Myopathies
A group of muscle diseases associated with abnormal mitochondria function.		02.0710
Auricular Fibrillation
[description not available]		02.4320
Atrial Fibrillation
Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.		02.4320
Black Fever
[description not available]		02.0810
Leishmaniasis, Visceral
A chronic disease caused by LEISHMANIA DONOVANI and transmitted by the bite of several sandflies of the genera Phlebotomus and Lutzomyia. It is commonly characterized by fever, chills, vomiting, anemia, hepatosplenomegaly, leukopenia, hypergammaglobulinemia, emaciation, and an earth-gray color of the skin. The disease is classified into three main types according to geographic distribution: Indian, Mediterranean (or infantile), and African.		02.0810
Muscle Tissue Neoplasms
[description not available]		02.4520
Actinic Reticuloid Syndrome
[description not available]		02.0710
Insulin Sensitivity
[description not available]		02.0710
Insulin Resistance
Diminished effectiveness of INSULIN in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent HYPERGLYCEMIA or KETOSIS.		02.0710
Basal Cell Cancer
[description not available]		04.3711
Sore Throat
[description not available]		03.8121
Pharyngitis
Inflammation of the throat (PHARYNX).		03.8121
Ganglioglioma
Rare indolent tumors comprised of neoplastic glial and neuronal cells which occur primarily in children and young adults. Benign lesions tend to be associated with long survival unless the tumor degenerates into a histologically malignant form. They tend to occur in the optic nerve and white matter of the brain and spinal cord.		04.0450
Aortic Stenosis
[description not available]		02.0110
Coronary Artery Vasospasm
[description not available]		02.420
Aortic Valve Stenosis
A pathological constriction that can occur above (supravalvular stenosis), below (subvalvular stenosis), or at the AORTIC VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.		02.0110
Coronary Vasospasm
Spasm of the large- or medium-sized coronary arteries.		07.420
Thrombocythemia
[description not available]		02.0110
Glaucoma, Angle Closure
[description not available]		02.0110
Orbital Diseases
Diseases of the bony orbit and contents except the eyeball.		02.4120
Optic Atrophy
Atrophy of the optic disk which may be congenital or acquired. This condition indicates a deficiency in the number of nerve fibers which arise in the RETINA and converge to form the OPTIC DISK; OPTIC NERVE; OPTIC CHIASM; and optic tracts. GLAUCOMA; ISCHEMIA; inflammation, a chronic elevation of intracranial pressure, toxins, optic nerve compression, and inherited conditions (see OPTIC ATROPHIES, HEREDITARY) are relatively common causes of this condition.		02.0110
Glaucoma, Angle-Closure
A form of glaucoma in which the intraocular pressure increases because the angle of the anterior chamber is blocked and the aqueous humor cannot drain from the anterior chamber.		02.0110
Histiocytosis, Non-Langerhans-Cell
Group of disorders which feature accumulations of active HISTIOCYTES and LYMPHOCYTES, but where the histiocytes are not LANGERHANS CELLS. The group includes HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SINUS HISTIOCYTOSIS; xanthogranuloma; reticulohistiocytoma; JUVENILE XANTHOGRANULOMA; xanthoma disseminatum; as well as the lipid storage diseases (SEA-BLUE HISTIOCYTE SYNDROME; and NIEMANN-PICK DISEASES).		02.0110
Acute Promyelocytic Leukemia
[description not available]		03.3870
Leukemia, Promyelocytic, Acute
An acute myeloid leukemia in which abnormal PROMYELOCYTES predominate. It is frequently associated with DISSEMINATED INTRAVASCULAR COAGULATION.		03.3870
Alopecia Circumscripta
[description not available]		02.9310
Alopecia Areata
Loss of scalp and body hair involving microscopically inflammatory patchy areas.		02.9310
Colitis, Ischemic
Inflammation of the COLON due to colonic ISCHEMIA resulting from alterations in systemic circulation or local vasculature.		02.4120
Blastoma, Pulmonary
[description not available]		02.4320
Nail Diseases
Diseases of the nail plate and tissues surrounding it. The concept is limited to primates.		02.0110
Meningitis, Meningococcal, Serogroup A
[description not available]		02.0110
Meningitis, Meningococcal
A fulminant infection of the meninges and subarachnoid fluid by the bacterium NEISSERIA MENINGITIDIS, producing diffuse inflammation and peri-meningeal venous thromboses. Clinical manifestations include FEVER, nuchal rigidity, SEIZURES, severe HEADACHE, petechial rash, stupor, focal neurologic deficits, HYDROCEPHALUS, and COMA. The organism is usually transmitted via nasopharyngeal secretions and is a leading cause of meningitis in children and young adults. Organisms from Neisseria meningitidis serogroups A, B, C, Y, and W-135 have been reported to cause meningitis. (From Adams et al., Principles of Neurology, 6th ed, pp689-701; Curr Opin Pediatr 1998 Feb;10(1):13-8)		02.0110
Leukemia L 1210
[description not available]		08.37320
Gangrene
Death and putrefaction of tissue usually due to a loss of blood supply.		02.0110
Diathesis
[description not available]		03.7921
Anemias, Iron-Deficiency
[description not available]		02.0110
Celiac Sprue
[description not available]		02.0110
Infections, Helicobacter
[description not available]		02.4320
Kelly's Syndrome
[description not available]		02.0110
Celiac Disease
A malabsorption syndrome that is precipitated by the ingestion of foods containing GLUTEN, such as wheat, rye, and barley. It is characterized by INFLAMMATION of the SMALL INTESTINE, loss of MICROVILLI structure, failed INTESTINAL ABSORPTION, and MALNUTRITION.		02.0110
Gastritis, Atrophic
GASTRITIS with atrophy of the GASTRIC MUCOSA, the GASTRIC PARIETAL CELLS, and the mucosal glands leading to ACHLORHYDRIA. Atrophic gastritis usually progresses from chronic gastritis.		02.0110
Helicobacter Infections
Infections with organisms of the genus HELICOBACTER, particularly, in humans, HELICOBACTER PYLORI. The clinical manifestations are focused in the stomach, usually the gastric mucosa and antrum, and the upper duodenum. This infection plays a major role in the pathogenesis of type B gastritis and peptic ulcer disease.		02.4320
Anemia, Iron-Deficiency
Anemia characterized by decreased or absent iron stores, low serum iron concentration, low transferrin saturation, and low hemoglobin concentration or hematocrit value. The erythrocytes are hypochromic and microcytic and the iron binding capacity is increased.		02.0110
Cochlear Diseases
Pathological processes of the snail-like structure (COCHLEA) of the inner ear (LABYRINTH) which can involve its nervous tissue, blood vessels, or fluid (ENDOLYMPH).		02.9140
Mesonephroma
A rare tumor of the female genital tract, most often the ovary, formerly considered to be derived from mesonephric rests. Two varieties are recognized: (1) clear cell carcinoma, so called because of its histologic resemblance to renal cell carcinoma, and now considered to be of muellerian duct derivation and (2) an embryonal tumor (called also ENDODERMAL SINUS TUMOR and yolk sac tumor), occurring chiefly in children. The latter variety may also arise in the testis. (Dorland, 27th ed)		03.8140
Anticipatory Vomiting
[description not available]		06.7364
Brown Tendon Sheath Syndrome
[description not available]		02.730
Acanthosis Nigricans
A circumscribed melanosis consisting of a brown-pigmented, velvety verrucosity or fine papillomatosis appearing in the axillae and other body folds. It occurs in association with endocrine disorders, underlying malignancy, administration of certain drugs, or as in inherited disorder.		02.0110
Cardiac Diseases
[description not available]		04.6632
Heart Diseases
Pathological conditions involving the HEART including its structural and functional abnormalities.		04.6632
P carinii Pneumonia
[description not available]		02.0110
Pneumonia, Pneumocystis
A pulmonary disease in humans occurring in immunodeficient or malnourished patients or infants, characterized by DYSPNEA, tachypnea, and HYPOXEMIA. Pneumocystis pneumonia is a frequently seen opportunistic infection in AIDS. It is caused by the fungus PNEUMOCYSTIS JIROVECII. The disease is also found in other MAMMALS where it is caused by related species of Pneumocystis.		02.0110
Hypospermatogenesis
[description not available]		02.0210
Sclera Diseases
[description not available]		03.8121
Kaposi Sarcoma
[description not available]		03.7921
AIDS-Associated Lymphoma
[description not available]		03.3420
Sarcoma, Kaposi
A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Kaposi's sarcoma occurs spontaneously in Jewish and Italian males in Europe and the United States. An aggressive variant in young children is endemic in some areas of Africa. A third form occurs in about 0.04% of kidney transplant patients. There is also a high incidence in AIDS patients. (From Dorland, 27th ed & Holland et al., Cancer Medicine, 3d ed, pp2105-7) HHV-8 is the suspected cause.		03.7921
Lymphoma, AIDS-Related
B-cell lymphoid tumors that occur in association with AIDS. Patients often present with an advanced stage of disease and highly malignant subtypes including BURKITT LYMPHOMA; IMMUNOBLASTIC LARGE-CELL LYMPHOMA; PRIMARY EFFUSION LYMPHOMA; and DIFFUSE, LARGE B-CELL, LYMPHOMA. The tumors are often disseminated in unusual extranodal sites and chromosomal abnormalities are frequently present. It is likely that polyclonal B-cell lymphoproliferation in AIDS is a complex result of EBV infection, HIV antigenic stimulation, and T-cell-dependent HIV activation.		03.3420
Pain, Intractable
Persistent pain that is refractory to some or all forms of treatment.		02.7130
Granulocytic Leukemia
[description not available]		011.762210
Leukemia, Myeloid
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.		011.762210
Osteolysis
Dissolution of bone that particularly involves the removal or loss of calcium.		02.0210
Granuloma, Plasma Cell, Orbital
[description not available]		02.0210
Orbital Pseudotumor
A nonspecific tumor-like inflammatory lesion in the ORBIT of the eye. It is usually composed of mature LYMPHOCYTES; PLASMA CELLS; MACROPHAGES; LEUKOCYTES with varying degrees of FIBROSIS. Orbital pseudotumors are often associated with inflammation of the extraocular muscles (ORBITAL MYOSITIS) or inflammation of the lacrimal glands (DACRYOADENITIS).		07.0210
Leukemia, Acute Monocytic
[description not available]		03.3220
Leukemia, Monocytic, Acute
An acute myeloid leukemia in which 80% or more of the leukemic cells are of monocytic lineage including monoblasts, promonocytes, and MONOCYTES.		03.3220
Chylothorax
The presence of chyle in the thoracic cavity. (Dorland, 27th ed)		02.0210
Urethral Obstruction
Partial or complete blockage in any part of the URETHRA that can lead to difficulty or inability to empty the URINARY BLADDER. It is characterized by an enlarged, often damaged, bladder with frequent urges to void.		02.0210
Granulomatosis, Lipid
[description not available]		02.0210
Erdheim-Chester Disease
A rare form of non-Langerhans-cell histiocytosis (HISTIOCYTOSIS, NON-LANGERHANS-CELL) with onset in middle age. The systemic disease is characterized by infiltration of lipid-laden macrophages, multinucleated giant cells, an inflammatory infiltrate of lymphocytes and histiocytes in the bone marrow, and a generalized sclerosis of the long bones.		02.0210
Abnormality, Torsion
[description not available]		02.0210
Pancoast Syndrome
A condition caused by an apical lung tumor (Pancoast tumor) with involvement of the nearby vertebral column and the BRACHIAL PLEXUS. Symptoms include pain in the shoulder and the arm, and atrophy of the hand.		04.7220
Asthenia
Clinical sign or symptom manifested as debility, or lack or loss of strength and energy.		03.411
Paralysis, Legs
[description not available]		02.0210
Paraplegia
Severe or complete loss of motor function in the lower extremities and lower portions of the trunk. This condition is most often associated with SPINAL CORD DISEASES, although BRAIN DISEASES; PERIPHERAL NERVOUS SYSTEM DISEASES; NEUROMUSCULAR DISEASES; and MUSCULAR DISEASES may also cause bilateral leg weakness.		02.0210
HbS Disease
[description not available]		02.9410
Anemia, Sickle Cell
A disease characterized by chronic hemolytic anemia, episodic painful crises, and pathologic involvement of many organs. It is the clinical expression of homozygosity for hemoglobin S.		02.9410
Li-Fraumeni Syndrome
Rare autosomal dominant syndrome characterized by mesenchymal and epithelial neoplasms at multiple sites. MUTATION of the p53 tumor suppressor gene, a component of the DNA DAMAGE response pathway, apparently predisposes family members who inherit it to develop certain cancers. The spectrum of cancers in the syndrome was shown to include, in addition to BREAST CANCER and soft tissue sarcomas (SARCOMA); BRAIN TUMORS; OSTEOSARCOMA; LEUKEMIA; and ADRENOCORTICAL CARCINOMA.		02.0210
Leukemia P388
An experimental lymphocytic leukemia originally induced in DBA/2 mice by painting with methylcholanthrene.		04.69110
Pachymeningitis
[description not available]		02.4320
Meningitis
Inflammation of the coverings of the brain and/or spinal cord, which consist of the PIA MATER; ARACHNOID; and DURA MATER. Infections (viral, bacterial, and fungal) are the most common causes of this condition, but subarachnoid hemorrhage (HEMORRHAGES, SUBARACHNOID), chemical irritation (chemical MENINGITIS), granulomatous conditions, neoplastic conditions (CARCINOMATOUS MENINGITIS), and other inflammatory conditions may produce this syndrome. (From Joynt, Clinical Neurology, 1994, Ch24, p6)		02.4320
Neoplasms, Nervous System
[description not available]		03.821
Adenocarcinoma, Scirrhous
An adenocarcinoma with a hard (Greek skirrhos, hard) structure owing to the formation of dense connective tissue in the stroma. (From Dorland, 27th ed)		02.0210
Suffocation
[description not available]		02.0210
Tracheal Stenosis
A pathological narrowing of the TRACHEA.		02.0210
Asphyxia
A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life.		02.0210
Bowel Diseases, Inflammatory
[description not available]		02.0210
Inflammatory Bowel Diseases
Chronic, non-specific inflammation of the GASTROINTESTINAL TRACT. Etiology may be genetic or environmental. This term includes CROHN DISEASE and ULCERATIVE COLITIS.		02.0210
Nerve Degeneration
Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.		02.6830
Aseptic Necrosis of Bone
[description not available]		03.8340
Osteonecrosis
Death of a bone or part of a bone, either atraumatic or posttraumatic.		03.8340
Polyarthritis
[description not available]		02.420
Fasciitis
Inflammation of the fascia. There are three major types: 1, Eosinophilic fasciitis, an inflammatory reaction with eosinophilia, producing hard thickened skin with an orange-peel configuration suggestive of scleroderma and considered by some a variant of scleroderma; 2, Necrotizing fasciitis (FASCIITIS, NECROTIZING), a serious fulminating infection (usually by a beta hemolytic streptococcus) causing extensive necrosis of superficial fascia; 3, Nodular/Pseudosarcomatous /Proliferative fasciitis, characterized by a rapid growth of fibroblasts with mononuclear inflammatory cells and proliferating capillaries in soft tissue, often the forearm; it is not malignant but is sometimes mistaken for fibrosarcoma.		07.730
Arthritis
Acute or chronic inflammation of JOINTS.		02.420
Branchial Cleft Cyst
[description not available]		02.0210
Acute Onset Vascular Dementia
[description not available]		03.4111
Dementia, Vascular
An imprecise term referring to dementia associated with CEREBROVASCULAR DISORDERS, including CEREBRAL INFARCTION (single or multiple), and conditions associated with chronic BRAIN ISCHEMIA. Diffuse, cortical, and subcortical subtypes have been described. (From Gerontol Geriatr 1998 Feb;31(1):36-44)		03.4111
Adiadochokinesis
[description not available]		02.0210
Fra(X) Syndrome
[description not available]		02.0210
Atrophy
Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes.		08.1350
Cerebellar Ataxia
Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)		02.0210
Fragile X Syndrome
A condition characterized genotypically by mutation of the distal end of the long arm of the X chromosome (at gene loci FRAXA or FRAXE) and phenotypically by cognitive impairment, hyperactivity, SEIZURES, language delay, and enlargement of the ears, head, and testes. INTELLECTUAL DISABILITY occurs in nearly all males and roughly 50% of females with the full mutation of FRAXA. (From Menkes, Textbook of Child Neurology, 5th ed, p226)		02.0210
Adenocarcinoma, Sebaceous
A malignant tumor composed of cells showing differentiation toward sebaceous epithelium. The tumor is solitary, firm, somewhat raised, more or less translucent, and covered with normal or slightly verrucose epidermis. It may be yellow or orange. The face and scalp are the commonest sites. The growth can be slow or rapid but metastasis is uncommon. Surgery cures most of the cases. (From Rook et al., Textbook of Dermatology, 4th ed, pp2403-4)		02.0210
Neoplasms, Sebaceous Gland
[description not available]		02.0210
Eyelid Neoplasms
Tumors of cancer of the EYELIDS.		02.0210
Experimental Hepatoma
[description not available]		03.150
Cardiomyopathy, Congestive
[description not available]		02.0210
Cardiomyopathy, Dilated
A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.		02.0210
Colitis Gravis
[description not available]		02.0210
Constriction, Pathological
[description not available]		02.0210
Colitis, Ulcerative
Inflammation of the COLON that is predominantly confined to the MUCOSA. Its major symptoms include DIARRHEA, rectal BLEEDING, the passage of MUCUS, and ABDOMINAL PAIN.		02.0210
Constriction, Pathologic
The condition of an anatomical structure's being constricted beyond normal dimensions.		02.0210
Bilateral Deafness
[description not available]		02.0210
Middle Ear Inflammation
[description not available]		02.0210
Otitis Media
Inflammation of the MIDDLE EAR including the AUDITORY OSSICLES and the EUSTACHIAN TUBE.		02.0210
Brain Abscess
A circumscribed collection of purulent exudate in the brain, due to bacterial and other infections. The majority are caused by spread of infected material from a focus of suppuration elsewhere in the body, notably the PARANASAL SINUSES, middle ear (see EAR, MIDDLE); HEART (see also ENDOCARDITIS, BACTERIAL), and LUNG. Penetrating CRANIOCEREBRAL TRAUMA and NEUROSURGICAL PROCEDURES may also be associated with this condition. Clinical manifestations include HEADACHE; SEIZURES; focal neurologic deficits; and alterations of consciousness. (Adams et al., Principles of Neurology, 6th ed, pp712-6)		02.0310
Infection, Postoperative Wound
[description not available]		02.0310
Aspergillosis, Nervous System Invasive
[description not available]		02.0310
Brain Ventricular Neoplasms
[description not available]		02.7230
Neuroaspergillosis
Infections of the nervous system caused by fungi of the genus ASPERGILLUS, most commonly ASPERGILLUS FUMIGATUS. Aspergillus infections may occur in immunocompetent hosts, but are more prevalent in individuals with IMMUNOLOGIC DEFICIENCY SYNDROMES. The organism may spread to the nervous system from focal infections in the lung, mastoid region, sinuses, inner ear, bones, eyes, gastrointestinal tract, and heart. Sinus infections may be locally invasive and enter the intracranial compartment, producing MENINGITIS, FUNGAL; cranial neuropathies; and abscesses in the frontal lobes of the brain. (From Joynt, Clinical Neurology, 1998, Ch 27, pp62-3)		02.0310
Autoimmune Disease
[description not available]		02.0310
Autoimmune Diseases
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.		02.0310
Leukemic Infiltration
A pathologic change in leukemia in which leukemic cells permeate various organs at any stage of the disease. All types of leukemia show various degrees of infiltration, depending upon the type of leukemia. The degree of infiltration may vary from site to site. The liver and spleen are common sites of infiltration, the greatest appearing in myelocytic leukemia, but infiltration is seen also in the granulocytic and lymphocytic types. The kidney is also a common site and of the gastrointestinal system, the stomach and ileum are commonly involved. In lymphocytic leukemia the skin is often infiltrated. The central nervous system too is a common site.		02.9410
Child Development Deviations
[description not available]		02.0310
Developmental Disabilities
Disorders in which there is a delay in development based on that expected for a given age level or stage of development. These impairments or disabilities originate before age 18, may be expected to continue indefinitely, and constitute a substantial impairment. Biological and nonbiological factors are involved in these disorders. (From American Psychiatric Glossary, 6th ed)		02.0310
Aneurysm, Ruptured
The tearing or bursting of the weakened wall of the aneurysmal sac, usually heralded by sudden worsening pain. The great danger of a ruptured aneurysm is the large amount of blood spilling into the surrounding tissues and cavities, causing HEMORRHAGIC SHOCK.		02.0310
Congenital Familial Lymphedema
[description not available]		02.0310
Lymphedema
Edema due to obstruction of lymph vessels or disorders of the lymph nodes.		02.0310
Cicatrization
The formation of fibrous tissue in the place of normal tissue during the process of WOUND HEALING. It includes scar tissue formation occurring in healing internal organs as well as in the skin after surface injuries.		02.0310
Cicatrix
The fibrous tissue that replaces normal tissue during the process of WOUND HEALING.		02.0310
Cronobacter Infections
[description not available]		02.0310
Enterobacteriaceae Infections
Infections with bacteria of the family ENTEROBACTERIACEAE.		02.0310
Granuloma Annulare
Benign granulomatous disease of unknown etiology characterized by a ring of localized or disseminated papules or nodules on the skin and palisading histiocytes surrounding necrobiotic tissue resulting from altered collagen structures.		02.9410
Acute Post-operative Pain
[description not available]		02.0310
Glomangioma
[description not available]		02.0310
Pain, Postoperative
Pain during the period after surgery.		02.0310
Diseases, Peripheral Vascular
[description not available]		02.4120
Peripheral Vascular Diseases
Pathological processes involving any one of the BLOOD VESSELS in the vasculature outside the HEART.		02.4120
Abdominal Hernia
[description not available]		02.0310
Respiratory Tract Fistula
An abnormal passage communicating between any component of the respiratory tract or between any part of the respiratory system and surrounding organs.		02.0310
Pleural Diseases
Diseases involving the PLEURA.		02.0310
Atypical Lipomatous Tumor
[description not available]		02.0310
Liposarcoma
A malignant tumor derived from primitive or embryonal lipoblastic cells. It may be composed of well-differentiated fat cells or may be dedifferentiated: myxoid (LIPOSARCOMA, MYXOID), round-celled, or pleomorphic, usually in association with a rich network of capillaries. Recurrences are common and dedifferentiated liposarcomas metastasize to the lungs or serosal surfaces. (From Dorland, 27th ed; Stedman, 25th ed)		02.0310
Anterior Ischemic Optic Neuropathy
[description not available]		02.0310
Optic Neuropathy, Ischemic
Ischemic injury to the OPTIC NERVE which usually affects the OPTIC DISK (optic neuropathy, anterior ischemic) and less frequently the retrobulbar portion of the nerve (optic neuropathy, posterior ischemic). The injury results from occlusion of arterial blood supply which may result from TEMPORAL ARTERITIS; ATHEROSCLEROSIS; COLLAGEN DISEASES; EMBOLISM; DIABETES MELLITUS; and other conditions. The disease primarily occurs in the sixth decade or later and presents with the sudden onset of painless and usually severe monocular visual loss. Anterior ischemic optic neuropathy also features optic disk edema with microhemorrhages. The optic disk appears normal in posterior ischemic optic neuropathy. (Glaser, Neuro-Ophthalmology, 2nd ed, p135)		02.0310
Ambulation Disorders, Neurologic
[description not available]		03.3420
Age-Related Memory Disorders
[description not available]		02.4420
Memory Disorders
Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with DEMENTIA; CRANIOCEREBRAL TRAUMA; ENCEPHALITIS; ALCOHOLISM (see also ALCOHOL AMNESTIC DISORDER); SCHIZOPHRENIA; and other conditions.		02.4420
Altered Level of Consciousness
[description not available]		02.0410
Anti-Phospholipid Antibody Syndrome
[description not available]		03.3520
Antiphospholipid Syndrome
The presence of antibodies directed against phospholipids (ANTIBODIES, ANTIPHOSPHOLIPID). The condition is associated with a variety of diseases, notably systemic lupus erythematosus and other connective tissue diseases, thrombopenia, and arterial or venous thromboses. In pregnancy it can cause abortion. Of the phospholipids, the cardiolipins show markedly elevated levels of anticardiolipin antibodies (ANTIBODIES, ANTICARDIOLIPIN). Present also are high levels of lupus anticoagulant (LUPUS COAGULATION INHIBITOR).		03.3520
Complication, Intraoperative
[description not available]		02.0310
Splenic Diseases
Diseases involving the SPLEEN.		02.0310
Neoplasm Regression, Spontaneous
Disappearance of a neoplasm or neoplastic state without the intervention of therapy.		02.0310
Bessel-Hagen Disease
[description not available]		02.0310
Experimental Radiation Injuries
[description not available]		04.6360
Granulomatosis, Wegener's
[description not available]		02.0310
Granulomatosis with Polyangiitis
A multisystemic disease of a complex genetic background. It is characterized by inflammation of the blood vessels (VASCULITIS) leading to damage in any number of organs. The common features include granulomatous inflammation of the RESPIRATORY TRACT and KIDNEYS. Most patients have measurable autoantibodies (ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES) against MYELOBLASTIN.		02.0310
Pleurisy, Tuberculous
[description not available]		02.0310
Acrocephalosyndactylia
Congenital craniostenosis with syndactyly.		02.9610
Cancer Syndromes, Hereditary
[description not available]		02.9610
Deficiency, Protein C
[description not available]		03.3320
Brain Hemorrhage, Cerebral
[description not available]		05.5532
Deficiency, Protein S
[description not available]		02.9510
Cerebral Hemorrhage
Bleeding into one or both CEREBRAL HEMISPHERES including the BASAL GANGLIA and the CEREBRAL CORTEX. It is often associated with HYPERTENSION and CRANIOCEREBRAL TRAUMA.		05.5532
Ectopic Hormone Syndromes
[description not available]		02.0310
Phlegmon
[description not available]		02.0310
Cellulitis
An acute, diffuse, and suppurative inflammation of loose connective tissue, particularly the deep subcutaneous tissues, and sometimes muscle, which is most commonly seen as a result of infection of a wound, ulcer, or other skin lesions.		07.0310
Bacteremia
The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion.		04.8742
Atresia, Biliary
[description not available]		02.0410
Biliary Atresia
Progressive destruction or the absence of all or part of the extrahepatic BILE DUCTS, resulting in the complete obstruction of BILE flow. Usually, biliary atresia is found in infants and accounts for one third of the neonatal cholestatic JAUNDICE.		02.0410
Myosarcoma
A general term for a malignant neoplasm derived from muscular tissue. (Stedman, 25th ed)		02.0310
CBS Deficiency
[description not available]		02.0310
Homocystinuria
Autosomal recessive inborn error of methionine metabolism usually caused by a deficiency of CYSTATHIONINE BETA-SYNTHASE and associated with elevations of homocysteine in plasma and urine. Clinical features include a tall slender habitus, SCOLIOSIS, arachnodactyly, MUSCLE WEAKNESS, genu varus, thin blond hair, malar flush, lens dislocations, an increased incidence of MENTAL RETARDATION, and a tendency to develop fibrosis of arteries, frequently complicated by CEREBROVASCULAR ACCIDENTS and MYOCARDIAL INFARCTION. (From Adams et al., Principles of Neurology, 6th ed, p979)		07.0310
Amentia
[description not available]		02.0310
Dementia
An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness.		02.0310
Facial Palsy
[description not available]		02.0310
Bronchiolitis, Exudative
[description not available]		02.0310
Bronchiolitis Obliterans
Inflammation of the BRONCHIOLES leading to an obstructive lung disease. Bronchioles are characterized by fibrous granulation tissue with bronchial exudates in the lumens. Clinical features include a nonproductive cough and DYSPNEA.		02.0310
EHS Tumor
[description not available]		03.3770
Refractory Anemia
[description not available]		02.0310
Anemia, Refractory
A severe sometimes chronic anemia, usually macrocytic in type, that does not respond to ordinary antianemic therapy.		02.0310
Graft-Versus-Host Disease
[description not available]		02.0310
BOOP
[description not available]		02.0310
Palatal Neoplasms
Tumors or cancer of the PALATE, including those of the hard palate, soft palate and UVULA.		02.4220
Graft vs Host Disease
The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.		02.0310
Leukemia, Myeloid, Acute, M4
[description not available]		02.0410
Leukemia, Myelomonocytic, Acute
A pediatric acute myeloid leukemia involving both myeloid and monocytoid precursors. At least 20% of non-erythroid cells are of monocytic origin.		02.0410
Atypical Endometrial Hyperplasia
A benign form of endometrial hyperplasia with increased number of cells with atypia. The atypical cells are large and irregular and have an increased nuclear/cytoplasmic ratio. The risk of progression to endometrial carcinoma rises with the increasing degree of cell atypia.		02.9510
Endometrial Hyperplasia
Benign proliferation of the ENDOMETRIUM in the UTERUS. Endometrial hyperplasia is classified by its cytology and glandular tissue. There are simple, complex (adenomatous without atypia), and atypical hyperplasia representing also the ascending risk of becoming malignant.		02.9510
Facial Dermatoses
Skin diseases involving the FACE.		03.4311
Angioblastic Meningioma
[description not available]		02.6930
Meningioma
A relatively common neoplasm of the CENTRAL NERVOUS SYSTEM that arises from arachnoidal cells. The majority are well differentiated vascular tumors which grow slowly and have a low potential to be invasive, although malignant subtypes occur. Meningiomas have a predilection to arise from the parasagittal region, cerebral convexity, sphenoidal ridge, olfactory groove, and SPINAL CANAL. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2056-7)		02.6930
Menopause
The last menstrual period. Permanent cessation of menses (MENSTRUATION) is usually defined after 6 to 12 months of AMENORRHEA in a woman over 45 years of age. In the United States, menopause generally occurs in women between 48 and 55 years of age.		03.4211
Epidermal Cyst
Intradermal or subcutaneous saclike structure, the wall of which is stratified epithelium containing keratohyalin granules.		03.4311
Neurocytoma
A benign brain tumor composed of neural elements which most often arise from the SEPTUM PELLUCIDUM and the walls of the lateral ventricles. Immunohistochemistry and electron microscopy evaluations may reveal expression of neuron specific enolase and synaptophysin and cells containing microtubuli, neurosecretory granules, and presynaptic vesicles. (From Acta Med Port 1994 Feb;7(2):113-9)		08.3320
Hypocalcemia
Reduction of the blood calcium below normal. Manifestations include hyperactive deep tendon reflexes, Chvostek's sign, muscle and abdominal cramps, and carpopedal spasm. (Dorland, 27th ed)		03.821
Cancer of Cecum
[description not available]		02.0410
Chloroma
[description not available]		02.0410
Sarcoma, Myeloid
An extramedullary tumor of immature MYELOID CELLS or MYELOBLASTS. Granulocytic sarcoma usually occurs with or follows the onset of ACUTE MYELOID LEUKEMIA.		02.0410
Cardiomyopathies, Primary
[description not available]		02.0410
Cardiomyopathies
A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).		02.0410
Experimental Leukemia
[description not available]		03.3670
Carcinoma, Bronchial
[description not available]		08.25117
Carcinoma, Bronchogenic
Malignant neoplasm arising from the epithelium of the BRONCHI. It represents a large group of epithelial lung malignancies which can be divided into two clinical groups: SMALL CELL LUNG CANCER and NON-SMALL-CELL LUNG CARCINOMA.		08.25117
Cancer of Lip
[description not available]		01.9810
Fatigue, Mental
[description not available]		01.9810
Periphlebitis
Periphlebitis is inflammation of the outer coat of a vein or of tissues surrounding the vein.		03.3711
Phlebitis
Inflammation of a vein, often a vein in the leg. Phlebitis associated with a blood clot is called (THROMBOPHLEBITIS).		03.3711
Ureteral Obstruction
Blockage in any part of the URETER causing obstruction of urine flow from the kidney to the URINARY BLADDER. The obstruction may be congenital, acquired, unilateral, bilateral, complete, partial, acute, or chronic. Depending on the degree and duration of the obstruction, clinical features vary greatly such as HYDRONEPHROSIS and obstructive nephropathy.		02.3920
Eosinophilia, Tropical
[description not available]		02.910
Eosinophilia
Abnormal increase of EOSINOPHILS in the blood, tissues or organs.		02.910
Di Guglielmo Disease
[description not available]		03.0850
Leukemia, Erythroblastic, Acute
A myeloproliferative disorder characterized by neoplastic proliferation of erythroblastic and myeloblastic elements with atypical erythroblasts and myeloblasts in the peripheral blood.		03.0850
Cystitis
Inflammation of the URINARY BLADDER, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain.		05.5432
Arrhythmia, Sinoatrial
[description not available]		01.9810
Pallor
A clinical manifestation consisting of an unnatural paleness of the skin.		01.9810
Neoplasms, Trophoblastic
[description not available]		04.6232
Enterocolitis
Inflammation of the MUCOSA of both the SMALL INTESTINE and the LARGE INTESTINE. Etiology includes ISCHEMIA, infections, allergic, and immune responses.		04.4751
Maxillary Neoplasms
Cancer or tumors of the MAXILLA or upper jaw.		01.9810
Infections, Staphylococcal
[description not available]		01.9810
Staphylococcal Infections
Infections with bacteria of the genus STAPHYLOCOCCUS.		01.9810
Congenital Epulides
[description not available]		01.9810
Leukemia, Lymphocytic, T Cell
[description not available]		03.5930
Leukemia, T-Cell
A malignant disease of the T-LYMPHOCYTES in the bone marrow, thymus, and/or blood.		03.5930
Dejerine-Roussy Syndrome
[description not available]		03.3711
Empyema, Gall Bladder
[description not available]		01.9810
Cholecystitis
Inflammation of the GALLBLADDER; generally caused by impairment of BILE flow, GALLSTONES in the BILIARY TRACT, infections, or other diseases.		01.9810
Digestive System Disorders
[description not available]		03.3711
Digestive System Diseases
Diseases in any part of the GASTROINTESTINAL TRACT or the accessory organs (LIVER; BILIARY TRACT; PANCREAS).		03.3711
Cranial Nerve II Diseases
[description not available]		02.3820
Optic Nerve Diseases
Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect.		02.3820
Plasma Cell Tumor
[description not available]		06.45110
Plasmacytoma
Any discrete, presumably solitary, mass of neoplastic PLASMA CELLS either in BONE MARROW or various extramedullary sites.		06.45110
Island Cell Tumor
[description not available]		03.3711
Apudoma
A general term collectively applied to tumors associated with the APUD CELLS series, irrespective of their specific identification.		03.3711
Adenoma, Islet Cell
A benign tumor of the pancreatic ISLET CELLS. Usually it involves the INSULIN-producing PANCREATIC BETA CELLS, as in INSULINOMA, resulting in HYPERINSULINISM.		03.3711
Angioma, Sclerosing
[description not available]		02.420
Histiocytoma, Benign Fibrous
A benign tumor composed, wholly or in part, of cells with the morphologic characteristics of HISTIOCYTES and with various fibroblastic components. Fibrous histiocytomas can occur anywhere in the body. When they occur in the skin, they are called dermatofibromas or sclerosing hemangiomas. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 5th ed, p1747)		02.420
Parathyroid Disorders
[description not available]		01.9810
Parathyroid Diseases
Pathological processes of the PARATHYROID GLANDS. They usually manifest as hypersecretion or hyposecretion of PARATHYROID HORMONE that regulates the balance of CALCIUM; PHOSPHORUS; and MAGNESIUM in the body.		01.9810
Branch Vein Occlusion
[description not available]		02.910
Retinal Vein Occlusion
Blockage of the RETINAL VEIN. Those at high risk for this condition include patients with HYPERTENSION; DIABETES MELLITUS; ATHEROSCLEROSIS; and other CARDIOVASCULAR DISEASES.		02.910
Desmoid
[description not available]		02.910
Fibromatosis, Aggressive
A childhood counterpart of abdominal or extra-abdominal desmoid tumors, characterized by firm subcutaneous nodules that grow rapidly in any part of the body but do not metastasize. The adult form of abdominal fibromatosis is FIBROMATOSIS, ABDOMINAL. (Stedman, 25th ed)		02.910
Abdominal Epilepsy
[description not available]		03.3711
Epilepsies, Partial
Conditions characterized by recurrent paroxysmal neuronal discharges which arise from a focal region of the brain. Partial seizures are divided into simple and complex, depending on whether consciousness is unaltered (simple partial seizure) or disturbed (complex partial seizure). Both types may feature a wide variety of motor, sensory, and autonomic symptoms. Partial seizures may be classified by associated clinical features or anatomic location of the seizure focus. A secondary generalized seizure refers to a partial seizure that spreads to involve the brain diffusely. (From Adams et al., Principles of Neurology, 6th ed, pp317)		03.3711
Angor Pectoris
[description not available]		01.9910
Angina Pectoris
The symptom of paroxysmal pain consequent to MYOCARDIAL ISCHEMIA usually of distinctive character, location and radiation. It is thought to be provoked by a transient stressful situation during which the oxygen requirements of the MYOCARDIUM exceed that supplied by the CORONARY CIRCULATION.		01.9910
Coma
A profound state of unconsciousness associated with depressed cerebral activity from which the individual cannot be aroused. Coma generally occurs when there is dysfunction or injury involving both cerebral hemispheres or the brain stem RETICULAR FORMATION.		01.9910
Male Genitourinary Diseases
[description not available]		01.9910
Neoplasms, Skull Base
[description not available]		01.9910
Chondrosarcoma, Mesenchymal
A rare aggressive variant of chondrosarcoma, characterized by a biphasic histologic pattern of small compact cells intermixed with islands of cartilaginous matrix. Mesenchymal chondrosarcomas have a predilection for flat bones; long tubular bones are rarely affected. They tend to occur in the younger age group and are highly metastatic. (DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1456)		01.9910
Teratocarcinoma
A malignant neoplasm consisting of elements of teratoma with those of embryonal carcinoma or choriocarcinoma, or both. It occurs most often in the testis. (Dorland, 27th ed)		01.9910
Angioimmunoblastic Lymphadenopathy
[description not available]		03.3811
Immunoblastic Lymphadenopathy
A disorder characterized by proliferation of arborizing small vessels, prominent immunoblastic proliferations and amorphous acidophilic interstitial material. Clinical manifestations include fever, sweats, weight loss, generalized lymphadenopathy and frequently hepatosplenomegaly.		03.3811
Brain Embolism and Thrombosis
[description not available]		01.9910
Arterial Obstructive Diseases
[description not available]		01.9910
Arterial Occlusive Diseases
Pathological processes which result in the partial or complete obstruction of ARTERIES. They are characterized by greatly reduced or absence of blood flow through these vessels. They are also known as arterial insufficiency.		01.9910
Mixed Tumor, Mesodermal
A sarcoma of the body of the uterus arising in older women, composed of more than one mesenchymal tissue, especially including striated muscle cells. It is associated with previous pelvic radiation exposure in 20% of patients. (Stedman, 25th ed; Holland et al., Cancer Medicine, 3d ed, p1702)		04.721
Cancer of Maxillary Sinus
[description not available]		04.721
Fibromatosis, Abdominal
A relatively large mass of unusually firm scarlike connective tissue resulting from active participation of fibroblasts, occurring most frequently in the abdominal muscles of women who have borne children. The fibroblasts infiltrate surrounding muscle and fascia. (Stedman, 25th ed)		03.7921
Adenoma, Prolactin-Secreting, Pituitary
[description not available]		01.9910
Anterior Optic Neuritis
[description not available]		01.9910
Drug Withdrawal Symptoms
[description not available]		01.9910
Optic Neuritis
Inflammation of the optic nerve. Commonly associated conditions include autoimmune disorders such as MULTIPLE SCLEROSIS, infections, and granulomatous diseases. Clinical features include retro-orbital pain that is aggravated by eye movement, loss of color vision, and contrast sensitivity that may progress to severe visual loss, an afferent pupillary defect (Marcus-Gunn pupil), and in some instances optic disc hyperemia and swelling. Inflammation may occur in the portion of the nerve within the globe (neuropapillitis or anterior optic neuritis) or the portion behind the globe (retrobulbar neuritis or posterior optic neuritis).		06.9910
Substance Withdrawal Syndrome
Physiological and psychological symptoms associated with withdrawal from the use of a drug after prolonged administration or habituation. The concept includes withdrawal from smoking or drinking, as well as withdrawal from an administered drug.		01.9910
Constrictive Pericarditis
[description not available]		01.9910
Infectious Myelitis
[description not available]		03.3811
Neuroectodermal Tumors
Malignant neoplasms arising in the neuroectoderm, the portion of the ectoderm of the early embryo that gives rise to the central and peripheral nervous systems, including some glial cells.		01.9910
Conductive Hearing Loss
[description not available]		01.9910
Foreign-Body Granuloma
[description not available]		03.3811
Berger Disease
[description not available]		02.9110
Glomerulonephritis, IGA
A chronic form of glomerulonephritis characterized by deposits of predominantly IMMUNOGLOBULIN A in the mesangial area (GLOMERULAR MESANGIUM). Deposits of COMPLEMENT C3 and IMMUNOGLOBULIN G are also often found. Clinical features may progress from asymptomatic HEMATURIA to END-STAGE KIDNEY DISEASE.		02.9110
Mandibular Fractures
Fractures of the lower jaw.		01.9910
Abscess, Psoas
[description not available]		01.9910
Edema, Laryngeal
[description not available]		03.7921
Laryngeal Edema
Abnormal accumulation of fluid in tissues of any part of the LARYNX, commonly associated with laryngeal injuries and allergic reactions.		03.7921
Cytomegalic Inclusion Disease
[description not available]		0210
Cytomegalovirus Infections
Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults.		0210
Placental-Site Trophoblastic Tumor
[description not available]		0210
Trophoblastic Tumor, Placental Site
An uncommon variant of CHORIOCARCINOMA. It is composed almost entirely of mononuclear cytotrophoblasts (TROPHOBLASTS). Because its secretion of hCG (CHORIONIC GONADOTROPIN) is low, a large tumor may develop before the hCG can be detected.		0210
Delayed Postpartum Hemorrhage
[description not available]		0210
Postpartum Hemorrhage
Excess blood loss from uterine bleeding associated with OBSTETRIC LABOR or CHILDBIRTH. It is defined as blood loss greater than 500 ml or of the amount that adversely affects the maternal physiology, such as BLOOD PRESSURE and HEMATOCRIT. Postpartum hemorrhage is divided into two categories, immediate (within first 24 hours after birth) or delayed (after 24 hours postpartum).		0210
Snoring
Rough, noisy breathing during sleep, due to vibration of the uvula and soft palate.		0210
Anemia, Hypoplastic
[description not available]		02.9110
Anemia, Aplastic
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.		02.9110
Muscular Weakness
[description not available]		0210
Muscle Weakness
A vague complaint of debility, fatigue, or exhaustion attributable to weakness of various muscles. The weakness can be characterized as subacute or chronic, often progressive, and is a manifestation of many muscle and neuromuscular diseases. (From Wyngaarden et al., Cecil Textbook of Medicine, 19th ed, p2251)		0210
Vision, Diminished
[description not available]		0210
Agnogenic Myeloid Metaplasia
[description not available]		0210
Primary Myelofibrosis
A de novo myeloproliferation arising from an abnormal stem cell. It is characterized by the replacement of bone marrow by fibrous tissue, a process that is mediated by CYTOKINES arising from the abnormal clone.		0210
Uremia
A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.		0210
Ph 1 Chromosome
[description not available]		03.3811
Leukemoid Reaction
A peripheral blood picture resembling that of leukemia or indistinguishable from it on the basis of morphologic appearance alone. (Dorland, 27th ed)		0210
A-V Dissociation
[description not available]		0210
Abnormal Deep Tendon Reflex
[description not available]		0210
Reflex, Abnormal
An abnormal response to a stimulus applied to the sensory components of the nervous system. This may take the form of increased, decreased, or absent reflexes.		0210
Ambiguous Genitalia
[description not available]		0210
Androgen Insensitivity Syndrome
[description not available]		0210
Disorders of Sex Development
In gonochoristic organisms, congenital conditions in which development of chromosomal, gonadal, or anatomical sex is atypical. Effects from exposure to abnormal levels of GONADAL HORMONES in the maternal environment, or disruption of the function of those hormones by ENDOCRINE DISRUPTORS are included.		0210
Barrett Epithelium
[description not available]		0210
Barrett Esophagus
A condition with damage to the lining of the lower ESOPHAGUS resulting from chronic acid reflux (ESOPHAGITIS, REFLUX). Through the process of metaplasia, the squamous cells are replaced by a columnar epithelium with cells resembling those of the INTESTINE or the salmon-pink mucosa of the STOMACH. Barrett's columnar epithelium is a marker for severe reflux and precursor to ADENOCARCINOMA of the esophagus.		0210
Angiomyolipoma
A benign tumor containing vascular, adipose, and muscle elements. It occurs most often in the kidney with smooth muscle elements (angiolipoleiomyoma) in association with tuberous sclerosis. (Dorland, 27th ed)		0210
Craniopharyngioma, Adamantinous
[description not available]		0210
Craniopharyngioma
A benign pituitary-region neoplasm that originates from Rathke's pouch. The two major histologic and clinical subtypes are adamantinous (or classical) craniopharyngioma and papillary craniopharyngioma. The adamantinous form presents in children and adolescents as an expanding cystic lesion in the pituitary region. The cystic cavity is filled with a black viscous substance and histologically the tumor is composed of adamantinomatous epithelium and areas of calcification and necrosis. Papillary craniopharyngiomas occur in adults, and histologically feature a squamous epithelium with papillations. (From Joynt, Clinical Neurology, 1998, Ch14, p50)		0210
Hypesthesia
Absent or reduced sensitivity to cutaneous stimulation.		0210
Melanoma, Amelanotic
An unpigmented malignant melanoma. It is an anaplastic melanoma consisting of cells derived from melanoblasts but not forming melanin. (Dorland, 27th ed; Stedman, 25th ed)		0210
Elevated ICP (Intracranial Pressure)
[description not available]		0210
Palsy
[description not available]		0210
Paralysis
A general term most often used to describe severe or complete loss of muscle strength due to motor system disease from the level of the cerebral cortex to the muscle fiber. This term may also occasionally refer to a loss of sensory function. (From Adams et al., Principles of Neurology, 6th ed, p45)		0210
Intracranial Hypertension
Increased pressure within the cranial vault. This may result from several conditions, including HYDROCEPHALUS; BRAIN EDEMA; intracranial masses; severe systemic HYPERTENSION; PSEUDOTUMOR CEREBRI; and other disorders.		0210
Cranial Nerve Diseases
Disorders of one or more of the twelve cranial nerves. With the exception of the optic and olfactory nerves, this includes disorders of the brain stem nuclei from which the cranial nerves originate or terminate.		03.3911
Shoulder Pain
Unilateral or bilateral pain of the shoulder. It is often caused by physical activities such as work or sports participation, but may also be pathologic in origin.		0210
Cystadenoma, Mucinous
A multilocular tumor with mucin secreting epithelium. They are most often found in the ovary, but are also found in the pancreas, appendix, and rarely, retroperitoneal and in the urinary bladder. They are considered to have low-grade malignant potential.		0210
Itching
[description not available]		0210
Tachyarrhythmia
[description not available]		0210
Pruritus
An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief.		0210
Tachycardia
Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.		0210
Cardiac Death
[description not available]		02.3920
Leukemia, Megakaryocytic
[description not available]		0210
Leukemia, Megakaryoblastic, Acute
An acute myeloid leukemia in which 20-30% of the bone marrow or peripheral blood cells are of megakaryocyte lineage. MYELOFIBROSIS or increased bone marrow RETICULIN is common.		0210
Flushing
A transient reddening of the face that may be due to fever, certain drugs, exertion, or stress.		04.3111
Viremia
The presence of viruses in the blood.		0210
Cancer of Jaw
[description not available]		0210
Edema, Fetal
[description not available]		0210
Hyperbilirubinemia, Hereditary
Inborn errors of bilirubin metabolism resulting in excessive amounts of bilirubin in the circulating blood, either because of increased bilirubin production or because of delayed clearance of bilirubin from the blood.		02.0110
Fibrosis, Inflammatory Perianeurysmal
[description not available]		01.9810
Retroperitoneal Fibrosis
A slowly progressive condition of unknown etiology, characterized by deposition of fibrous tissue in the retroperitoneal space compressing the ureters, great vessels, bile duct, and other structures. When associated with abdominal aortic aneurysm, it may be called chronic periaortitis or inflammatory perianeurysmal fibrosis.		06.9810
Candida Infection
[description not available]		03.3611
Candidiasis
Infection with a fungus of the genus CANDIDA. It is usually a superficial infection of the moist areas of the body and is generally caused by CANDIDA ALBICANS. (Dorland, 27th ed)		03.3611
Adenoma, beta-Cell
[description not available]		01.9810
Insulinoma
A benign tumor of the PANCREATIC BETA CELLS. Insulinoma secretes excess INSULIN resulting in HYPOGLYCEMIA.		06.9810
Acute Kidney Tubular Necrosis
[description not available]		03.5830
Kidney Tubular Necrosis, Acute
Acute kidney failure resulting from destruction of EPITHELIAL CELLS of the KIDNEY TUBULES. It is commonly attributed to exposure to toxic agents or renal ISCHEMIA following severe TRAUMA.		03.5830
Skin Ulcer
An ULCER of the skin and underlying tissues.		01.9810
Paraganglioma, Gangliocytic
[description not available]		02.3720
Paraganglioma
A neural crest tumor usually derived from the chromoreceptor tissue of a paraganglion, such as the carotid body, or medulla of the adrenal gland (usually called a chromaffinoma or pheochromocytoma). It is more common in women than in men. (Stedman, 25th ed; from Segen, Dictionary of Modern Medicine, 1992)		02.3720
Respiratory Tract Neoplasms
New abnormal growth of tissue in the RESPIRATORY SYSTEM.		03.3611
Incontinentia Pigmenti Achromians
[description not available]		01.9710
Carcinoma 256, Walker
A transplantable carcinoma of the rat that originally appeared spontaneously in the mammary gland of a pregnant albino rat, and which now resembles a carcinoma in young transplants and a sarcoma in older transplants. (Stedman, 25th ed)		02.3720
Central Nervous System Disease
[description not available]		03.3611
Central Nervous System Diseases
Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord.		03.3611
Mitral Stenosis
[description not available]		01.9710
Mitral Valve Stenosis
Narrowing of the passage through the MITRAL VALVE due to FIBROSIS, and CALCINOSIS in the leaflets and chordal areas. This elevates the left atrial pressure which, in turn, raises pulmonary venous and capillary pressure leading to bouts of DYSPNEA and TACHYCARDIA during physical exertion. RHEUMATIC FEVER is its primary cause.		01.9710
Reticulum Cell-Like Sarcoma, Yoshida
[description not available]		01.9710
Leukemia, Lymphocytic
[description not available]		02.3720
Leukemia, Lymphoid
Leukemia associated with HYPERPLASIA of the lymphoid tissues and increased numbers of circulating malignant LYMPHOCYTES and lymphoblasts.		02.3720
Fetal Death
Death of the developing young in utero. BIRTH of a dead FETUS is STILLBIRTH.		01.9710
Fetal Growth Restriction
[description not available]		01.9710
Fetal Growth Retardation
Failure of a FETUS to attain expected GROWTH.		01.9710
Hydronephrosis
Abnormal enlargement or swelling of a KIDNEY due to dilation of the KIDNEY CALICES and the KIDNEY PELVIS. It is often associated with obstruction of the URETER or chronic kidney diseases that prevents normal drainage of urine into the URINARY BLADDER.		01.9710
Herpes Simplex Virus Infection
[description not available]		01.9710
Herpes Simplex
A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. (Dorland, 27th ed.)		01.9710