| Trial | Phase | Enrollment | Study Type | Start Date | Status |
|---|
| Phase II, Randomized, Open-label Study of the IGF-1R Inhibitor AXL1717 Compared to Docetaxel in Patients With Previously Treated, Locally Advanced, or Metastatic Squamous Cell Carcinoma or Adenocarcinoma of the Lung [NCT01561456] | Phase 2 | 100 participants (Actual) | Interventional | 2011-12-31 | Completed |
| 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) | Interventional | 2019-08-01 | Recruiting |
| Randomized Multicenter Study Comparing 6xFEC With 3xFEC-3xDoc in High-risk Node-negative Patients With Operable Breast Cancer: Comparison of Efficacy and Evaluation of Clinico-pathological and Biochemical Markers as Risk Selection Criteria [NCT01222052] | Phase 3 | 4,150 participants (Actual) | Interventional | 2002-01-31 | Active, not recruiting |
| Randomized, Multicentre Phase II Trial of the Sequencing of Radium-223 and Docetaxel Plus Prednisone in Symptomatic Bone-only Metastatic Castration-resistant Prostate Cancer (mCRPC) [NCT03230734] | Phase 2 | 70 participants (Anticipated) | Interventional | 2017-09-01 | Recruiting |
| The Efficacy and Safety of Neoadjuvant Pegylated Liposomal Doxorubicin Plus Cyclophosphamide Followed by Docetaxel in Breast Cancer Patients: A Multicentric, Open-label, Non-randomized Concurrent Control, Non-inferiority Trial [NCT03123770] | Phase 4 | 384 participants (Anticipated) | Interventional | 2016-12-31 | Recruiting |
| A Phase I/II Study of Obatoclax Mesylate (GX15-070MS) Administered Every 3 Weeks in Combination With Docetaxel to Patients With Relapsed or Refractory Non-Small Cell Lung Cancer (NSCLC) [NCT00405951] | Phase 1/Phase 2 | 47 participants (Actual) | Interventional | 2006-10-31 | Completed |
| Weekly Administration of (bi-)Daily Oral Docetaxel in Combination With Ritonavir in Patients With Normal or Impaired Liver Function [NCT05084456] | Phase 1 | 0 participants (Actual) | Interventional | 2017-07-31 | Withdrawn(stopped due to Pending further development) |
| A Phase II/III Study of N-803 (ALT-803) Plus Pembrolizumab Versus Standard of Care in Participants With Stage IV or Recurrent Non-Small Cell Lung Cancer Previously Treated With Anti-PD-1 or Anti-PD-L1 Therapy (Lung-MAP Non-Match Sub-Study) [NCT05096663] | Phase 2/Phase 3 | 82 participants (Actual) | Interventional | 2022-03-15 | Active, not recruiting |
| Cardiac Safety and Efficacy for Early-stage Breast Cancer Patients Treated With Pegylated Liposomal Doxorubicin（PLD）：an Dynamic Randomized, Positive Control, Open, Multicenter Clinical Study [NCT03949634] | Phase 3 | 272 participants (Anticipated) | Interventional | 2017-09-01 | Recruiting |
| A Phase I Trial of Docetaxel and Sirolimus in Patients With Advanced Malignancies [NCT01054313] | Phase 1 | 103 participants (Actual) | Interventional | 2010-01-31 | Completed |
| A Phase II Trial of Neoadjuvant Bevacizumab, Docetaxel and Carboplatin for Triple Negative Breast Cancer (Neat Trial) [NCT01208480] | Phase 2 | 45 participants (Actual) | Interventional | 2010-09-30 | Completed |
| A Prospective, Open and Unicentric Phase II Clinical Trial of Docetaxel Combined With Oxaliplatin for Triple Negative Local Advanced Breast Cancer Patients (TNLABC) [NCT01216124] | | 0 participants | Expanded Access | | Available |
| A Prospective, Phase II Trial of Induction Chemotherapy With Docetaxel/Cisplatin for Masaoka Stage III/IV Thymic Epithelial Tumors [NCT01312324] | Phase 2 | 27 participants (Actual) | Interventional | 2007-02-28 | Completed |
| A Multicenter, Randomized, Open-Label Phase 3 Study to Investigate the Efficacy and Safety of Aldoxorubicin Compared to Investigator's Choice in Subjects With Metastatic, Locally Advanced, or Unresectable Soft Tissue Sarcomas Who Either Relapsed or Were R [NCT02049905] | Phase 3 | 433 participants (Actual) | Interventional | 2014-01-31 | Completed |
| A Randomized Multicenter Phase II/III Study of Optimized Treatment Strategies for Stage II and III Nasopharyngeal Carcinoma [NCT03908372] | Phase 2/Phase 3 | 120 participants (Anticipated) | Interventional | 2019-06-15 | Recruiting |
| A Phase 1 Study of Liposome Encapsulated Docetaxel (LE-DT) in Patients With Advanced Solid Tumors [NCT01151384] | Phase 1 | 30 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Phase I Study of Chemo-Immunotherapy in Patients With Relapsed and Refractory Head and Neck Squamous Cell Carcinoma [NCT01149902] | Phase 1 | 10 participants (Anticipated) | Interventional | 2010-07-31 | Recruiting |
| Phase II Study of Concurrent Chemoradiotherapy Using IMRT (With Single Photon Emission Computed Tomography/SPECT-CT to Define Functional Lung Volume and Positron Emission Tomography/PET to Define Gross Tumour Volume/GTV) and Docetaxel-cisplatin (or Carbop [NCT01266512] | Phase 2 | 34 participants (Actual) | Interventional | 2011-01-31 | Completed |
| A Phase 2, Randomized, Non-Comparative, Two-Arm Open Label, Multiple-Center Study Of CP-751,871 In Combination With Docetaxel/Prednisone In Chemotherapy- Naive (Arm A) And Docetaxel/Prednisone Refractory (Arm B) Patients With Hormone Insensitive Prostate [NCT00313781] | Phase 2 | 204 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Randomized Phase II Trial of 4-regimen (SP, FL/Tax, FL/Doc, FOLFOX) in Patients With Recurrent or Metastatic Gastric Cancer [NCT01283204] | Phase 2 | 180 participants (Actual) | Interventional | 2010-03-09 | Completed |
| A Phase III, Randomized, Double-Blinded, Multi-Center, Study to Assess the Efficacy of Docetaxel (TAXOTERE™) in Combination With ZD6474 (ZACTIMA™) Versus Docetaxel (TAXOTERE™) With Placebo in Subjects With Locally Advanced or Metastatic NSCLC [NCT00312377] | Phase 3 | 1,690 participants (Actual) | Interventional | 2006-05-31 | Completed |
| A Phase 1, Pharmacokinetic Study of STA-9090 in Combination With Docetaxel in Subjects With Advanced Solid Tumor Malignancies [NCT01183364] | Phase 1 | 27 participants (Actual) | Interventional | 2010-07-31 | Completed |
| 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 2 | 7 participants (Actual) | Interventional | 2013-12-19 | Terminated(stopped due to Loss of study funding) |
| FOcal Radiation for Oligometastatic Castration-rEsistant Prostate Cancer (FORCE): A Phase II Randomized Trial [NCT03556904] | Phase 2 | 13 participants (Actual) | Interventional | 2018-12-10 | Active, not recruiting |
| "A Multicenter Phase II Study of Capecitabine and Docetaxel for Previously Treated Pancreatic Cancer Patients CapTere" [NCT00290693] | Phase 2 | 45 participants (Actual) | Interventional | 2004-07-31 | Completed |
| An Open-Label, Multi-Center Phase I/II Study of the Safety and Tolerability of the Combination of Trastuzumab-MCC-DM1 (T-DM1) With Docetaxel, and Potentially Pertuzumab, for Treatment for Patients With Advanced Breast Cancer [NCT00934856] | Phase 1/Phase 2 | 98 participants (Actual) | Interventional | 2009-07-31 | Completed |
| 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 2 | 43 participants (Actual) | Interventional | 2005-12-05 | Completed |
| Phase III Study to Compare Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Vinorelbine With Trastuzumab-biosimilar (Kanjinti®) Plus Pertuzumab Plus Docetaxel as First-line Treatment for HER2-positive Advanced Breast Cancer [NCT03811418] | Phase 3 | 0 participants (Actual) | Interventional | 2019-01-31 | Withdrawn(stopped due to Study approved with treatment regimen based on current guidelines. However, reimbursement of IMP was not feasible.) |
| Phase I Trial to Compare Pharmacokinetics and Safety of SYP-0704A With Taxotere in Subjects With Advanced Solid Tumor [NCT01336582] | Phase 1 | 42 participants (Actual) | Interventional | 2009-08-31 | Completed |
| A Multi-center Phase II Trial to Evaluate the Efficacy and Safety of Neoadjuvant Chemotherapy With DoceTaxel(Doxotel) and Gemcitabine(Gemcibine)in Locally Advanced Breast Cancer [NCT01352494] | Phase 2 | 99 participants (Anticipated) | Interventional | 2011-05-31 | Not yet recruiting |
| A Randomized, Phase IIB/III Study of Ganetespib (STA-9090) in Combination With Docetaxel Versus Docetaxel Alone in Subjects With Stage IIIb or IV Non-Small-Cell Lung Cancer [NCT01348126] | Phase 2/Phase 3 | 385 participants (Actual) | Interventional | 2011-05-31 | Terminated |
| A Randomized, Phase III Study Comparing TAC (Docetaxel, Doxorubicin, Cyclophosphamide) With TCX ( Docetaxel, Cyclophosphamide, Capecitabine) as Adjuvant Treatment for Node-Positive Her2-Negative Breast Cancer [NCT01354522] | Phase 3 | 400 participants (Anticipated) | Interventional | 2011-05-31 | Recruiting |
| A Phase 2, Double-Blind, Placebo-Controlled Study of IPI-504 and Docetaxel in Previously Treated Patients With Stage IIIB or IV Non-Small Cell Lung Cancer [NCT01362400] | Phase 2 | 226 participants (Actual) | Interventional | 2011-05-31 | Completed |
| A Randomized Phase II Study of Perioperative Atezolizumab +/- Chemotherapy in Resectable MSI-H/dMMR Gastric and Gastroesophageal Junction (GEJ) Cancer [NCT05836584] | Phase 2 | 240 participants (Anticipated) | Interventional | 2024-06-08 | Recruiting |
| 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 1 | 130 participants (Anticipated) | Interventional | 2022-06-17 | Recruiting |
| A Phase III Randomized Trial of Eribulin (NSC #707389) With or Without Gemcitabine Versus Standard of Care (Physician's Choice) for Treatment of Metastatic Urothelial Carcinoma Refractory to, or Ineligible for, Anti PD1/PDL1 Therapy [NCT04579224] | Phase 3 | 465 participants (Anticipated) | Interventional | 2021-06-28 | Suspended(stopped due to Other - New treatment available, eliminating Arm 2) |
| A Randomized Phase II Trial of Cabozantinib and Cabozantinib Plus Nivolumab Versus Standard Chemotherapy in Patients With Previously Treated Non-Squamous NSCLC [NCT04310007] | Phase 2 | 117 participants (Anticipated) | Interventional | 2020-07-13 | Active, not recruiting |
| The Registry to Observe Clinical Outcomes of Patients With High-risk Metastatic Hormone-naïve Prostate Cancer in Japan [NCT04034095] | | 979 participants (Actual) | Observational [Patient Registry] | 2019-07-08 | Active, not recruiting |
| A Phase 3 Study of Erdafitinib Compared With Vinflunine or Docetaxel or Pembrolizumab in Subjects With Advanced Urothelial Cancer and Selected FGFR Gene Aberrations [NCT03390504] | Phase 3 | 629 participants (Actual) | Interventional | 2018-03-23 | Active, not recruiting |
| A Randomized, Double-Blind, Phase III Trial of Taxane/Trastuzumab/Pertuzumab With Atezolizumab or Placebo in First-Line HER2-Positive Metastatic Breast Cancer [NCT03199885] | Phase 3 | 600 participants (Anticipated) | Interventional | 2019-04-05 | Active, not recruiting |
| A Phase II Trial of Trametinib With Docetaxel in Patients With KRAS Mutation Positive Non-Small Cell Lung Cancer (NSCLC) and Progressive Disease Following One or Two Prior Systemic Therapies [NCT02642042] | Phase 2 | 60 participants (Actual) | Interventional | 2016-07-18 | Active, 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 3 | 315 participants (Actual) | Interventional | 2014-01-15 | Active, not recruiting |
| A Randomized Phase III Trial of Adjuvant Therapy Comparing Chemotherapy Alone (Six Cycles of Docetaxel Plus Cyclophosphamide or Four Cycles of Doxorubicin Plus Cyclophosphamide Followed by Weekly Paclitaxel) to Chemotherapy Plus Trastuzumab in Women With [NCT01275677] | Phase 3 | 3,270 participants (Actual) | Interventional | 2011-01-06 | Active, 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 3 | 403 participants (Actual) | Interventional | 2008-08-08 | Active, not recruiting |
| 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 1 | 102 participants (Actual) | Interventional | 2010-03-31 | Completed |
| A Randomized Multicenter Phase II/III Study Comparing 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) Versus Epirubicin, Cisplatin and 5-FU (ECF) in Patients With Locally Advanced Resectable Adenocarcinoma of the Esophagogastreal Junction or the Stomac [NCT01216644] | Phase 2/Phase 3 | 716 participants (Actual) | Interventional | 2010-08-31 | Completed |
| A Phase II Trial of Concurrent Chemoradiotherapy With Weekly Docetaxel and Cisplatin for Locally Advanced Head and Neck Cancer [NCT01126008] | Phase 2 | 44 participants (Actual) | Interventional | 2009-11-16 | Completed |
| An Open-Label, Randomized, Multicenter, Phase II, Non Comparative, Exploratory Study on Neoadjuvant Treatment With Trastuzumab Plus Docetaxel Plus Bevacizumab According to Positon Emission Tomography (PET) Value Modification in Patients With Early Stage H [NCT01142778] | Phase 2 | 152 participants (Actual) | Interventional | 2010-05-19 | Completed |
| SIMCAP (Surgery in Metastatic Carcinoma of Prostate): Phase 2.5 Multi-Institution Randomized Prospective Clinical Trial Evaluating the Impact of Cytoreductive Radical Prostatectomy Combined With Best Systemic Therapy on Oncologic and Quality of Life Outco [NCT03456843] | Phase 2 | 190 participants (Anticipated) | Interventional | 2018-03-14 | Recruiting |
| Phase II Study of Concurrent Cisplatin/Pemetrexed and RT Followed by Docetaxel in Stage III NSCLC (Non Small Cell Lung Cancer) [NCT00301808] | Phase 2 | 29 participants (Actual) | Interventional | 2005-11-30 | Completed |
| 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 3 | 150 participants (Anticipated) | Interventional | 2022-05-23 | Recruiting |
| "A Phase Ib Dose Escalation, Open Label, Multicenter Study Evaluating LDE225 (Sonidegib) in Combination With Docetaxel in Triple Negative (TN) Advanced Breast Cancer (ABC) Patients EDALINE" [NCT02027376] | Phase 1 | 12 participants (Actual) | Interventional | 2014-05-31 | Completed |
| [NCT01257139] | Phase 3 | 490 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Tratamiento Individualizado en función de Las Mutaciones en EGFR y Del Nivel de expresión de BRCA1 en Pacientes Con Adenocarcinoma de pulmón Avanzado [NCT00883480] | | 153 participants (Actual) | Interventional | 2005-06-30 | Completed |
| A Randomized, Multicenter, Phase II Trial of Cisplatin, Irinotecan and Bevacizumab (PCA) vs. Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer [NCT00911820] | Phase 2 | 88 participants (Actual) | Interventional | 2009-07-31 | Completed |
| ESSAI DE PHASE III RANDOMISE EVALUANT LE FOLFOX AVEC OU SANS DOCETAXEL (TFOX) EN 1ère LIGNE DE CHIMIOTHERAPIE DES ADENOCARCINOMES OESO-GASTRIQUES LOCALEMENT AVANCES OU METASTATIQUES [NCT03006432] | Phase 3 | 507 participants (Actual) | Interventional | 2016-12-19 | Active, not recruiting |
| Randomised Phase II Study of the Combination of Oral Vinorelbine With Capecitabine Versus Gemcitabine in Combination With Paclitaxel Versus Gemcitabine in Combination With Docetaxel as First Line Chemotherapy in Patients With Metastatic Breast Cancer [NCT03887130] | Phase 2 | 152 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Phase I Dose Escalation Trial of Biweekly Alimta (With Vitamin Supplementation) in Combination With Taxotere in Advanced Solid Tumor Patients [NCT01172028] | Phase 1 | 33 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Randomized Phase II Trial of Neoadjuvant Combination Chemotherapy of DCS (Cisplatin + Docetaxel + S-1) and DCF (Docetaxel + Cisplatin + 5-FU) in Patients With Locally Advanced Gastric Adenocarcinoma [NCT01286766] | Phase 2 | 6 participants (Actual) | Interventional | 2009-09-30 | Completed |
| A Multicenter, Open-Label, Phase II Study of LE-DT for Efficacy and Safety in Patients With Metastatic Castrate Resistant Prostate Cancer [NCT01188408] | Phase 2 | 0 participants (Actual) | Interventional | 2010-06-30 | Withdrawn(stopped due to Study shut-down in 12/2010 when NeoPharm merged with Insys.) |
| A Phase 1 Study of 1-Methyl-D-tryptophan (NSC-721782) in Combination With Docetaxel in Metastatic Solid Tumors [NCT01191216] | Phase 1 | 27 participants (Actual) | Interventional | 2010-09-30 | Completed |
| 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) | Interventional | 2019-03-01 | Not yet recruiting |
| A Phase 2 Study of Gefitinib Compared With Pemetrexed/Cisplatin in Advanced Non-Small Cell Lung Cancer Patients [NCT01192230] | Phase 2 | 30 participants (Anticipated) | Interventional | 2009-06-30 | Recruiting |
| Phase I/II Study With Temsirolimus Versus no add-on in Patients With Castration Resistant Prostate Cancer (CRPC) Receiving First-line Docetaxel Chemotherapy [NCT01206036] | Phase 1/Phase 2 | 19 participants (Actual) | Interventional | 2010-07-31 | Completed |
| Early Detection of Chemotherapy Induced Cardiac Damage in Elderly Patients With Early Breast Cancer: a Randomized Phase II Trial Comparing (Neo) Adjuvant Epirubicin-cyclophosphamide (EC) Versus Docetaxel (Taxotere)-Cyclophosphamide (TC.) [NCT01301040] | Phase 2 | 2 participants (Actual) | Interventional | 2011-03-31 | Terminated(stopped due to Slow recruitment) |
| A Phase 1 and Pharmacologic Study of MM-111 in Combination With Multiple Treatment Regimens in Patients With Advanced HER2 Positive Solid Tumors [NCT01304784] | Phase 1 | 100 participants (Anticipated) | Interventional | 2011-01-31 | Completed |
| Phase II Study of Patients With Peritoneal Carcinomatosis From Gastric Cancer Treated With Preoperative Systemic Chemotherapy Followed by Peritonectomy and Intraperitoneal Chemotherapy [NCT01379482] | Phase 2 | 18 participants (Actual) | Interventional | 2005-01-31 | Completed |
| 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 2 | 127 participants (Actual) | Interventional | 2007-03-31 | Completed |
| Phase II Multicenter Randomized Two-arm Study of Capmatinib and Spartalizumab Combination Therapy vs Docetaxel in Pretreated Adult Patients With EGFR Wild-type ALK Rearrangement Negative Advanced/Metastatic Non-small Cell Lung Cancer [NCT03647488] | Phase 2 | 18 participants (Actual) | Interventional | 2018-12-26 | Completed |
| A Phase I/II, Open-label, Two Part Study of GSK3359609 in Combination With Tremelimumab in Participants With Selected, Advanced Solid Tumors [NCT03693612] | Phase 1/Phase 2 | 26 participants (Actual) | Interventional | 2018-11-26 | Completed |
| A Biomarker-Driven Master Protocol for Previously Treated Squamous Cell Lung Cancer (Lung-Map) [NCT02154490] | | 1,864 participants (Actual) | Observational | 2014-07-08 | Completed |
| Anlotinib Combined With Docetaxel For Advanced Non-Small Cell Lung Cancer After The Failure Of Platinum-Based Doublet-Chemotherapy [NCT03735264] | Phase 2 | 46 participants (Anticipated) | Interventional | 2018-11-15 | Not yet recruiting |
| Randomized, OpEn-Label, Active-ContrOl Trial of SPI-2012 (Eflapegrastim) Versus Pegfilgrastim in the Management of Chemotherapy-Induced Neutropenia in Early-Stage BReast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) (RECOVER) [NCT02953340] | Phase 3 | 237 participants (Actual) | Interventional | 2017-05-10 | Completed |
| A Phase II Trial of Induction Chemoradiotherapy With Cisplatin/Etoposide Followed by Surgical Resection, Followed by Docetaxel, for Non-Small Cell Lung Cancer Involving the Superior Sulcus (Pancoast Tumors) [NCT00062439] | Phase 2 | 46 participants (Actual) | Interventional | 2003-07-31 | Completed |
| 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 3 | 3,222 participants (Actual) | Interventional | 2001-04-30 | Completed |
| Cyclophosphamide and Docetaxel Every 3 Weeks as Neoadjuvant Therapy in Locally Advanced Breast Cancer, A Collaborative Trial [NCT01229605] | Phase 2 | 0 participants (Actual) | Interventional | 2010-10-31 | Withdrawn(stopped due to Study was not a good fit for the patient population seen at this hospital.) |
| A Phase 1 Study to Evaluate the Effects of Rifampin on Pharmacokinetics of Pevonedistat in Patients With Advanced Solid Tumors [NCT03486314] | Phase 1 | 20 participants (Actual) | Interventional | 2018-08-13 | Completed |
| Docetaxel (NSC-628503) And Vinorelbine (NSC-608210) Plus Filgrastim (NSC-614629) With Weekly Trastuzumab (NSC-688097) For HER-2 Positive, Stage IV Breast Cancer [NCT00041067] | Phase 2 | 76 participants (Actual) | Interventional | 2002-09-30 | Completed |
| A Phase 3,Randomized, Double-blinded, Placebo-controlled Study to Evaluate Efficacy and Safety of Pyrotinib Plus Trastuzumab and Docetaxel Versus Placebo Plus Trastuzumab and Docetaxel in Patients With HER2 Positive MBC. [NCT03863223] | Phase 3 | 590 participants (Actual) | Interventional | 2019-04-22 | Active, not recruiting |
| Activity of CYP3A and Genotypes of CYP3A5 and MDR1 as Predictors of the Clearance and Adverse Effects of Docetaxel, and the Effect of Docetaxel to CYP3A Activity in Previously Untreated Breast Cancer Patients [NCT01110291] | | 20 participants (Actual) | Observational | 2003-04-30 | Completed |
| Multimodal Therapy With and Without Cetuximab in Patients With Locally Advanced Esophageal Carcinoma - An Open-Label Phase III Trial [NCT01107639] | Phase 3 | 297 participants (Actual) | Interventional | 2010-05-27 | Completed |
| A Phase II Study of AZD4547 for Previously Treated FGFR-Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study) [NCT02965378] | Phase 2/Phase 3 | 43 participants (Actual) | Interventional | 2014-10-31 | Completed |
| Androgen Deprivation Withdrawal Versus Maintenance and Intermittent Chemotherapy Versus Continuous in Prostate Cancer Patients With Castrate Resistant Disease [NCT01224405] | Phase 3 | 600 participants (Anticipated) | Interventional | 2010-04-30 | Active, not recruiting |
| Survival Analysis of A Chinese Randomized Crossover Study Comparing Erlotinib to Docetaxel/Cisplatin in Previously Untreated Stage IIIB/IV Lung Adenocarcinoma With EGFR Mutations [NCT01131429] | Phase 2 | 60 participants (Anticipated) | Interventional | 2010-06-30 | Not yet recruiting |
| Randomized Phase II Trial of Sunitinib and Docetaxel in Advanced Gastric Cancer Patients Who Had Prior Chemotherapy With Fluoropyrimidine and Platinum [NCT01238055] | Phase 2 | 116 participants (Actual) | Interventional | 2008-11-30 | Completed |
| A Phase 3, Open-Label, Randomized Study to Compare Adjuvant Chemotherapy of Docetaxel/Capecitabine/Oxaliplatin Versus Capecitabine/Oxaliplatin in Advanced Gastric Cancer Patients at Stage IIIB and IV (M0) (Based on AJCC Ed. 6) Who Received Radical Resecti [NCT01935778] | Phase 3 | 286 participants (Anticipated) | Interventional | 2013-10-02 | Recruiting |
| Modified FLOT Chemotherapy as First-line Treatment in Advanced or Metastatic Gastric Cancer [NCT03606928] | Phase 1/Phase 2 | 18 participants (Actual) | Interventional | 2018-07-01 | Completed |
| "Randomized Phase II Study Evaluating the Feasibility of a Chemotherapy With Docetaxel-Prednisone in a Weekly Schedule or Every 3 Weeks, for Castration-resistant Metastatic Prostate Cancer Elderly Patients (>=75), Vulnerable or Frail , as Defined by the C [NCT01254513] | Phase 2 | 66 participants (Actual) | Interventional | 2010-12-09 | Completed |
| Phase II Trial of Pevonedistat (TAK-924) Plus Docetaxel in Patients With Previously Treated Advanced Non-Small Cell Lung Cancer [NCT03228186] | Phase 2 | 40 participants (Actual) | Interventional | 2018-03-05 | Terminated(stopped due to Pharmaceutical company discontinued the study drug.) |
| A Phase 1, Double-blinded, Randomised, Multi-centre, Three-period, Three-treatment, Crossover Study to Compare the Intravenous Pharmacokinetic and Safety Characteristics of European Taxotere® and American Taxotere® With Hospira Docetaxel Injection Adminis [NCT01268163] | Phase 1 | 32 participants (Actual) | Interventional | 2007-08-31 | Completed |
| A Phase II Study of Induction Docetaxel, Cisplatin, Cetuximab and Bevacizumab (TPE-A) Followed by Concurrent Radiation, Cisplatin, Cetuximab and Bevacizumab (XPE-A) in Patients With Locally Advanced Head and Neck Cancer (CTRC# 11-36) [NCT01588431] | Phase 2 | 5 participants (Actual) | Interventional | 2011-12-31 | Active, not recruiting |
| A Randomized, Multicenter, Open-label, Phase III Trial of Docetaxel and S1 (DS) Versus S1 and Cisplatin (SP) in Curatively Resected (D2) Gastric Cancer of Stage IIIB/IV (M0) [NCT01283217] | Phase 3 | 166 participants (Anticipated) | Interventional | 2010-03-31 | Recruiting |
| A Phase I/II Dose-Escalation and Efficacy/Safety Study of Afuresertib Plus Sintilimab Plus Chemotherapy in Patients With Selected Solid Tumors That Resistance to Prior Anti-PD-1/PD-L1 Treatment [NCT05383482] | Phase 1/Phase 2 | 167 participants (Anticipated) | Interventional | 2022-06-30 | Recruiting |
| A Multicenter, Open-Label, Phase II Study of LE-DT for Efficacy and Safety in Patients With Locally Advanced or Metastatic Pancreatic Cancer [NCT01186731] | Phase 2 | 40 participants (Actual) | Interventional | 2010-04-30 | Completed |
| Docetaxel Plus 6-month Androgen Suppression and Radiation Therapy Versus 6-month Androgen Suppression and Radiation Therapy for Patients With High Risk Localized or Locally Advanced Prostate Cancer: A Randomized Controlled Trial [NCT00116142] | Phase 3 | 350 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Total Neoadjuvant Chemotherapy With 5-fluoruracil, Leucovorin, Oxaliplatin and Docetaxel in Locally Advanced Gastric and Gastroesophageal Junction Cancer (OCTASUR): Randomized, Single Center, Open Label Trial, Phase 2/3 [NCT06028737] | Phase 2/Phase 3 | 758 participants (Anticipated) | Interventional | 2023-08-25 | Recruiting |
| A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Docetaxel Versus Placebo + Docetaxel as Treatment for Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) [NCT05348577] | Phase 3 | 790 participants (Anticipated) | Interventional | 2022-03-25 | 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 3 | 1,367 participants (Actual) | Interventional | 2018-12-18 | Active, not recruiting |
| A Phase II Trial of ADI-PEG 20 in Combination With Gemcitabine and Docetaxel for the Treatment of Soft Tissue Sarcoma Osteosarcoma, Ewing's Sarcoma, and Small Cell Lung Cancer [NCT03449901] | Phase 2 | 98 participants (Actual) | Interventional | 2018-05-09 | Completed |
| Phase II Study of Docetaxel and Capecitabine in Advanced Squamous Cell Carcinoma of the Head and Neck [NCT02524275] | Phase 2 | 14 participants (Actual) | Interventional | 2015-03-30 | Terminated(stopped due to low enrollment) |
| A Multicenter Phase II Study, to Evaluate the Predictive Markers of Response in Locally Advanced Breast Cancer, Treated With Bevacizumab Combined With Neoadjuvant Chemotherapy [NCT01338753] | Phase 2 | 74 participants (Actual) | Interventional | 2009-10-31 | Completed |
| RAGE Inhibition to Decrease Cancer Therapy Related Cardio Toxicity in Women With Early Breast Cancer [NCT05256745] | Phase 1/Phase 2 | 48 participants (Anticipated) | Interventional | 2023-06-06 | Recruiting |
| Multicentre Randomized Phase II Study of Neoadjuvant Trastuzumab Plus Docetaxel With and Without Bevacizumab and Trastuzumab Plus Docetaxel Plus Non-pegylated Liposome-encapsulated Doxorubicin (NPLD) With and Without Bevacizumab in HER2-positive Early Bre [NCT01367028] | Phase 2 | 100 participants (Actual) | Interventional | 2011-06-30 | Completed |
| The Effectiveness and Safety of Intravesical Docetaxel Instillation After Operation to Prevent Intravesical Recurrence After Radical Nephroureterectomy or Distal Ureterectomy in Upper Urinary Tract Urothelial Carcinoma: A Prospective Study [NCT03209206] | Phase 2 | 84 participants (Anticipated) | Interventional | 2017-06-28 | Recruiting |
| Phase I/II Study With the Combination of Afatinib and Selumetinib in Advanced KRAS Mutant Positive and PIK3CA Wildtype Non-small Cell Lung Cancer [NCT02450656] | Phase 1/Phase 2 | 320 participants (Anticipated) | Interventional | 2015-06-30 | Recruiting |
| SAMSUNG MEDICAL CENTER [NCT02447380] | Phase 2 | 2 participants (Actual) | Interventional | 2017-07-10 | Completed |
| A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation [NCT04165031] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2019-11-28 | Terminated(stopped due to The study was terminated due to an unexpected toxicity finding.) |
| A Phase 1b (Open-Label)/Phase 2 (Randomized, Double-Blinded) Study Evaluating Gemcitabine and Docetaxel With or Without Olaratumab in the Treatment of Advanced Soft Tissue Sarcoma [NCT02659020] | Phase 1/Phase 2 | 310 participants (Actual) | Interventional | 2016-03-01 | Completed |
| A Randomized, Multicenter, Controlled, Adaptive II/III Study to Compare Neoadjuvant Chemotherapy of Docetaxel，Oxaliplatin Combined With S-1(DOS) Versus Oxaliplatin Combined With S-1(SOX)in Locally Advanced Gastric Adenocarcinoma (RESOLVE-2 Study) [NCT03691454] | Phase 2/Phase 3 | 258 participants (Anticipated) | Interventional | 2018-06-28 | Active, not recruiting |
| A Clinical Phase I, Open-label, PET Study With [89Zr]-Df-CriPec® Docetaxel in Patients With Solid Tumours to Assess Biodistribution and Tumour Accumulation of [89Zr]-Df-CriPec® Docetaxel [NCT03712423] | Phase 1 | 7 participants (Actual) | Interventional | 2018-04-01 | Completed |
| A Phase II Study of Docetaxel Combined With Cisplatin as the First Line Chemotherapy in Patients With Metastatic Non-small Cell Lung Cancer [NCT01356303] | Phase 2 | 50 participants (Anticipated) | Interventional | 2009-03-31 | Suspended(stopped due to Difficulty in enrolling patients) |
| A Single-center, Prospective, Randomized Study of Adjuvant Paclitaxel and Trastuzumab Versus Docetaxel and Trastuzumab in Stage I HER2 Positive Breast Cancer [NCT05189067] | Phase 2/Phase 3 | 190 participants (Anticipated) | Interventional | 2022-01-31 | Recruiting |
| Single Arm Phase II Study of Docetaxel and Lapatinib in Metastatic Transitional Cell Carcinoma in Bladder as Second Line Treatment [NCT01382706] | Phase 2 | 15 participants (Actual) | Interventional | 2011-06-13 | Terminated(stopped due to Trial not progressing toward scientific goals) |
| A Phase III Randomized Controlled Trial to Compare BL-B01D1 With Physician's Choice of Chemotherapy (Last Line) in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma (NPC) Previously Treated With PD-1/PD-L1 Monoclonal Antibody and at Least Two [NCT06118333] | Phase 3 | 368 participants (Anticipated) | Interventional | 2023-12-04 | Recruiting |
| A Phase II, Open-label, Platform Study, to Evaluate Immunotherapy-based Combinations in Participants With Advanced Non-Small Cell Lung Cancer [NCT05676931] | Phase 2 | 320 participants (Anticipated) | Interventional | 2023-02-01 | Recruiting |
| Phase 3 Randomized Study of DS-1062a Versus Docetaxel in Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-LUNG01) [NCT04656652] | Phase 3 | 590 participants (Anticipated) | Interventional | 2020-12-21 | Active, 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 2 | 377 participants (Actual) | Interventional | 2017-06-26 | Completed |
| Neoadjuvant Phase II Study of Pembrolizumab And Carboplatin Plus Docetaxel in Triple Negative Breast Cancer [NCT03639948] | Phase 2 | 121 participants (Actual) | Interventional | 2018-09-04 | Active, not recruiting |
| Open-label, Randomized, Active-controlled, Multicenter, Phase III Clinical Trial to Compare the Efficacy and the Safety of AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Taxotere Versus AC(Doxorubicin, Cyclophosphamide) Followed by 4 Cycles Nanoxe [NCT05207514] | Phase 3 | 320 participants (Anticipated) | Interventional | 2022-02-01 | Not yet recruiting |
| A Randomized, Open-label, Two-period, Crossover Trial to Compare the Pharmacokinetic Profiles Between Albumin-bound Docetaxel and Taxotere in Patients With Advanced Solid Tumors [NCT04811118] | Phase 1 | 27 participants (Actual) | Interventional | 2021-05-18 | Active, not recruiting |
| 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 2 | 50 participants (Anticipated) | Interventional | 2018-10-01 | Recruiting |
| A Randomized, Controlled, Single Center Clinical Trial to Evaluate the Efficacy and Safety of Neoadjuvant Therapy With Androgen Deprivation Therapy Combined With Docetaxel for High Risk and Very High Risk Prostate Cancer [NCT04869371] | Phase 2 | 75 participants (Anticipated) | Interventional | 2018-12-12 | Active, not recruiting |
| 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 3 | 3,509 participants (Actual) | Interventional | 2008-04-30 | Terminated |
| A Phase III, Randomized Open-Label Study to Compare the Pharmacokinetics, Efficacy, and Safety of Subcutaneous (SC) Trastuzumab With Intravenous (IV) Trastuzumab Administered in Women With HER2-Positive Early Breast Cancer (EBC) [NCT00950300] | Phase 3 | 596 participants (Actual) | Interventional | 2009-10-16 | Completed |
| Efficacy and Safety of Anlotinib Versus Docetaxel in Advanved Non-squamous Non-small-cell Lung Cancer Without EGFR Mutation Who Failed in First-line Platinum-based Doublet Chemotherapy: an Open, Muti-center, Randomized Controlled Trial [NCT03703596] | Phase 2 | 88 participants (Anticipated) | Interventional | 2018-10-16 | Not yet recruiting |
| A Randomized, Phase 3 Study of Poziotinib in Previously Treated Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) Harboring HER2 Exon 20 Mutations (PINNACLE) [NCT05378763] | Phase 3 | 268 participants (Anticipated) | Interventional | 2022-05-12 | Suspended(stopped due to The study has not enrolled any patients. The study design is under discussion and will likely be redesigned in consultation with the FDA.) |
| A Prospective, Open-label, Non-inferiority Study to Evaluate Injectable Albumin-bound Paclitaxel Versus Docetaxel for the Adjuvant Treatment of Breast Cancer [NCT05420467] | Phase 4 | 2,413 participants (Anticipated) | Interventional | 2022-07-10 | Recruiting |
| Xenotransplantation of Primary Cancer Samples in Zebrafish Embryos [NCT03668418] | | 120 participants (Anticipated) | Observational | 2018-06-01 | Recruiting |
| Chemotherapy Plus Pembrolizumab After Progression With Previous PD-1/PD-L1 Inhibitors in Patients With Advanced Non-small Cell Lung Cancer: Placebo-controlled Randomized Phase II Study [NCT03656094] | Phase 2 | 98 participants (Anticipated) | Interventional | 2018-11-01 | Recruiting |
| Adjuvant 6 Cycles of Docetaxel and Cyclophosphamide or 3 Cycles of Cyclophosphamide/Epirubicin/Fluorouracil Followed by 3 Cycles of Docetaxel Versus 4 Cycles of Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel in HER2-negative Operable Breast [NCT01314833] | Phase 3 | 1,570 participants (Actual) | Interventional | 2010-06-01 | Completed |
| A Phase 1b Clinical Study of the Dual MDMX/MDM2 Inhibitor, ALRN-6924, as a Chemoprotection Agent in Patients With TP53-Mutated, HER2 Negative Breast Cancer Receiving Neoadjuvant or Adjuvant Chemotherapy With Docetaxel, Doxorubicin, and Cyclophosphamide (T [NCT05622058] | Phase 1 | 6 participants (Actual) | Interventional | 2023-01-09 | Terminated(stopped due to The study has been terminated early given that the first four patients enrolled have experienced Grade 4 neutropenia and alopecia after cycle 1 and as such failed to meet the primary endpoint and the main secondary endpoint.) |
| DORA: A Phase I and Randomized Phase II Study of Docetaxel and RAD001 (Everolimus) in Advanced/Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck [NCT01313390] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2009-06-30 | Terminated(stopped due to Lack of recruitment) |
| Randomized Trial of Comparing One Cycle With Three Cycles Induction Chemotherapy Using Docetaxel, Cisplatin and Fluorouracil in Locoregionally Advanced Nasopharyngeal Carcinoma [NCT02096380] | | 120 participants (Anticipated) | Observational [Patient Registry] | 2014-05-31 | Not 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 1 | 0 participants (Actual) | Interventional | 2014-06-30 | Withdrawn |
| A Multicenter Phase III Randomized Trial Comparing Docetaxel in Combination With Doxorubicin and Cyclophosphamide Versus Doxorubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Treatment of Operable Breast Cancer HER2neu Negative Patients With [NCT00312208] | Phase 3 | 3,299 participants (Actual) | Interventional | 2001-11-30 | Completed |
| A Randomized Pilot Phase II Study of Docetaxel Alone or in Combination With PANVAC(Trademark)-V (Vaccinia) and PANVAC(Trademark)-F (Fowlpox) in Adults With Metastatic Breast Cancer [NCT00179309] | Phase 2 | 48 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Randomized, Phase II Study of Definitive Radiotherapy With Concurrent Cisplatin vs. Docetaxel-cetuximab in Locally Advanced Head and Neck Squamous Cell Carcinoma: an ERCC1 Biomarker Enrichment and Interaction Design [NCT02128906] | Phase 2 | 160 participants (Anticipated) | Interventional | 2013-12-31 | Recruiting |
| Anlotinib Plus Chemotherapy as First-line Therapy for Gastrointestinal Tumor Patients With Unresectable Liver Metastasis: A Multi-cohort, Multi-center Clinical Trial (ALTER-G-001) [NCT05262335] | Phase 2 | 116 participants (Anticipated) | Interventional | 2021-12-01 | Recruiting |
| A Phase IIa, Open-Label, Single- Center Study to Assess the Activity of Oshadi D and Oshadi R in Combination With Docetaxel, as 2nd Line Therapy for Metastatic Non Small Cell Lung Cancer [NCT02134990] | Phase 2 | 20 participants (Anticipated) | Interventional | 2014-06-30 | Recruiting |
| An Open Label, Two Treatment, Two Period, Two Sequence,Crossover, Bioequivalence Study of BH009 Against Winthrop (Docetaxel) Injection in Patients With Solid Tumors [NCT04889599] | Phase 3 | 46 participants (Actual) | Interventional | 2021-04-29 | Completed |
| Dose Climbing Trial of Anlotinib Plus Pemetrexed/Docetaxel in the Second-line Treatment of Advanced Gene Negative Non-squamous Non-small Cell Lung Cancer [NCT03566576] | | 18 participants (Anticipated) | Interventional | 2018-07-01 | Not yet recruiting |
| Abiraterone Acetate Maintenance in Combination With Docetaxel After Disease Progression to Abiraterone Acetate in Metastatic Castration Resistant Prostate Cancer. Randomized Phase II Study. [NCT02036060] | Phase 2 | 119 participants (Actual) | Interventional | 2014-02-07 | Completed |
| Phase 2 Study of Neoadjuvant Bevacizumab Plus DOF Versus DOF in Local Advanced Gastric Carcinoma and Its Association With Circulating Tumor Cell [NCT02048540] | Phase 1/Phase 2 | 86 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Randomized Open Non Comparative Multicenter Phase II Study of Sequential Erlotinib With Docetaxel Versus Docetaxel Alone in Second Line of Treatment in Patients With Non Small Cell Lung Cancer After Failure of First Line Chemotherapy [NCT01350817] | Phase 2 | 156 participants (Actual) | Interventional | 2011-05-31 | Completed |
| An Open-label, Multi-center Phase II Trial to Evaluate the Efficacy and Safety of Combination Chemotherapy With DoceTaxel(Detaxel) and Oxaliplatin(Oxalitin)in Recurrent or Metastatic Breast Cancer [NCT01351597] | Phase 2 | 51 participants (Anticipated) | Interventional | 2011-04-30 | Recruiting |
| Phase II Study of Docetaxel, Oxaliplatin, Capecitabine With Bevacizumab and Trastuzumab in Case of Human Epidermal Growth Factor Receptor 2 (HER2)-Positivity in Patients With Locally Advanced or Metastatic Gastric Cancer or Adenocarcinoma of the Gastro-oe [NCT01359397] | Phase 2 | 0 participants | Interventional | 2011-03-31 | Active, not recruiting |
| [NCT02099396] | Phase 2/Phase 3 | 100 participants (Anticipated) | Interventional | 2014-04-30 | Not yet recruiting |
| An Open-label, Randomized, Multi-center, Phase III Clinical Study of MRG002 Versus Investigator's Choice of Chemotherapy in the Treatment of Patients With HER2-positive Unresectable Locally Advanced or Metastatic Urothelial Cancer Previously Treated With [NCT05754853] | Phase 3 | 290 participants (Anticipated) | Interventional | 2023-04-06 | Recruiting |
| The Management of Metastatic Neck Nodes in N2/3 Hypopharyngeal Squamous Cell Carcinoma: A Multi-center Randomized Controlled Prospective Study [NCT05494190] | | 111 participants (Anticipated) | Interventional | 2022-11-01 | Recruiting |
| Tislelizumab Combined With Docetaxel for Cross-line Treatment of First-line Resistant Advanced NSCLC，a Phase II Clinical Study [NCT05192681] | Phase 2 | 35 participants (Anticipated) | Interventional | 2021-10-10 | Enrolling by invitation |
| Randomized Phase II Trial of Single Agent Chemotherapy Plus Nivolumab or Single Agent Chemotherapy Alone in Patients With Advanced Squamous or Non-squamous NSCLC With Primary Resistance to Prior PD-1 or PDL-1 Inhibitor [NCT03041181] | Phase 2 | 3 participants (Actual) | Interventional | 2017-01-27 | Terminated(stopped due to Funder decision - lack of accrual) |
| A Randomized, Multicenter, Open-Label, Phase III Trial Comparing Trastuzumab Plus Pertuzumab Plus a Taxane Following Anthracyclines Versus Trastuzumab Emtansine Plus Pertuzumab Following Anthracyclines as Adjuvant Therapy in Patients With Operable HER2-Po [NCT01966471] | Phase 3 | 1,846 participants (Actual) | Interventional | 2014-01-31 | Completed |
| 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 3 | 174 participants (Actual) | Interventional | 2007-02-28 | Completed |
| 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 4 | 110 participants (Actual) | Interventional | 2015-08-18 | Completed |
| Docetaxel, Irinotecan, Recurrent, Refractory, Bone and Soft Tissue Sarcomas [NCT01380275] | Phase 2 | 35 participants (Anticipated) | Interventional | 2008-04-30 | Recruiting |
| Anlotinib Plus Docetaxel Versus Docetaxel for Treatment of EGFR Wild-type Advanced Non-small-cell Lung Cancer After Disease Progression on Platinum-based Therapy : a Multicentre, Double-blind, Randomised Explorative Trial [NCT03624309] | Phase 2 | 84 participants (Anticipated) | Interventional | 2018-10-15 | Recruiting |
| Ib Dose Finding Study of LDE225 Plus Docetaxel/Prednisone in Patients With Advanced or Metastatic Castration Resistant Prostate Cancer Who Experience Disease Progression After Receiving Docetaxel [NCT02182622] | Phase 1 | 0 participants (Actual) | Interventional | 2014-07-31 | Withdrawn |
| 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 2 | 98 participants (Anticipated) | Interventional | 2014-06-30 | Active, not recruiting |
| A Randomized Phase 2 Trial of Doxorubicin Plus Pemetrexed Followed by Docetaxel, Versus Doxorubicin Plus Cyclophosphamide Followed by Docetaxel, as Neoadjuvant Treatment for Early Breast Cancer [NCT00149214] | Phase 2 | 257 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Phase II Trial Evaluating Weekly Docetaxel and Capecitabine in Patients With Metastatic or Advanced, Locally, Recurrent Head and Neck Cancer [NCT00148122] | Phase 2 | 40 participants (Actual) | Interventional | 2002-11-30 | Completed |
| Dose Determination of Taxotere®, Eloxatin® and Xeloda® (TEX)in Combination With Herceptin® as First-line Treatment for Patients With HER2 Positive Non-resectable Oesophagus, Cardia or Gastric Cancer (ECV) [NCT01295086] | | 27 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Randomized Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) With Cetuximab +/- Docetaxel Followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT02057107] | Phase 2 | 40 participants (Actual) | Interventional | 2013-07-03 | Completed |
| 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 1 | 53 participants (Actual) | Interventional | 2010-05-31 | Completed |
| Randomized Phase II Study of Ixabepilone Plus Trastuzumab vs. Docetaxel Plus Trastuzumab in Female Subjects With Her2+ Locally Advanced and/or Metastatic Breast Cancer [NCT00490646] | Phase 2 | 50 participants (Actual) | Interventional | 2008-02-29 | Completed |
| A Phase I/II Study of MGCD265 in Combination With Erlotinib or Docetaxel in Subjects With Advanced Malignancies and in Subjects With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00975767] | Phase 1 | 126 participants (Actual) | Interventional | 2009-08-31 | Terminated(stopped due to The study was terminated due to a need for a reformulation of the study drug. Phase 1 completed, no patients enrolled in Phase 2.) |
| A Randomized Double-Blinded Placebo Controlled Phase III Trial Comparing Doctaxel and Prednisone With and Without Bevacizumab (IND #7921, NSC #704865) in Men With Hormone Refractory Prostate Cancer [NCT00110214] | Phase 3 | 1,050 participants (Actual) | Interventional | 2005-04-30 | Completed |
| A Phase II Trial Evaluating Biweekly Docetaxel and DeGramont Regimen in First-Line Treatment of Unresectable or Metastatic Gastric Adenocarcinoma (DaeMon) [NCT01567618] | Phase 2 | 39 participants (Actual) | Interventional | 2012-03-31 | Completed |
| A Phase 1/2 Safety And Pharmacokinetic Study Of SU011248 In Combination With Docetaxel (Taxotere) And Prednisone In Patients With Metastatic Hormone Refractory Prostate Cancer (HRPC) [NCT00137436] | Phase 1/Phase 2 | 93 participants (Actual) | Interventional | 2005-10-31 | Completed |
| Phase II Study of The Efficacy And Safety of Chloroquine (C) in CombinAtion With Taxane or Taxane-like (T) Chemo Agents in The Treatment of Patients With Advanced or Metastatic Breast Cancer Who Have Failed Anthracycline Chemo Base Therapy [NCT01446016] | Phase 2 | 38 participants (Actual) | Interventional | 2011-09-30 | Completed |
| A Phase II Study to Evaluate Overall Response Rate of BAY 43-9006 (Sorafenib) Combined With Docetaxel and Cisplatin or Oxaliplatin in the Treatment of Metastatic or Advanced Unresectable Gastric and Gastroesophageal Junction (GEJ) Adenocarcinoma [NCT00253370] | Phase 2 | 44 participants (Actual) | Interventional | 2005-10-31 | Completed |
| Guidance of Adjuvant Instillation in Intermediate Risk Non-muscle Invasive Bladder Cancer by Drug Screens in Patient Derived Organoids. A Single Center, Open-label, Phase II Trial With a Feasibility Endpoint. (GAIN-INST-TRIAL) [NCT05024734] | Phase 2 | 33 participants (Anticipated) | Interventional | 2022-11-17 | Recruiting |
| Anlotinib Combined With Docetaxel as Second-line Treatment of Patients With Wild-type Advanced Non-squamous NSCLC [NCT03750916] | Phase 2 | 46 participants (Anticipated) | Interventional | 2018-11-30 | Not yet recruiting |
| A Phase II Evaluation of Gemcitabine (NSC #613327) and Docetaxel (NSC # 628503) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus [NCT00114218] | Phase 2 | 28 participants (Actual) | Interventional | 2005-03-31 | Completed |
| A Phase II Trial of Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) in Metastatic Esophageal and Gastric Cancer [NCT00394433] | Phase 2 | 38 participants (Actual) | Interventional | 2006-09-30 | Completed |
| A Randomized Controlled Study of Docetaxel Monotherapy or Docetaxel and DOXIL for the Treatment of Advanced Breast Cancer [NCT00091442] | Phase 3 | 751 participants (Actual) | Interventional | 2004-09-30 | Completed |
| A Multicenter Open-label, Phase I/II Dose Escalation Study of Oral Lapatinib in Combination With Docetaxel in Patients With HER-2 Positive Advanced or Metastatic Breast Cancer [NCT01044485] | Phase 1/Phase 2 | 17 participants (Actual) | Interventional | 2008-11-30 | Completed |
| A Phase III Randomized Trial of Docetaxel Based Induction Chemotherapy in Patients With N2/N3 Locally Advanced Head and Neck Cancer [NCT00117572] | Phase 3 | 285 participants (Actual) | Interventional | 2004-11-30 | Completed |
| A Randomized Phase-II Pilot Trial of Docetaxel and Prednisone Versus Radiation Therapy Plus Docetaxel and Prednisone in Patients With Nonmetastatic and Oligometastatic Castrate Resistant Prostate Cancer [NCT01087580] | Phase 2 | 0 participants (Actual) | Interventional | 2011-03-31 | Withdrawn |
| Randomized Phase III Study of Docetaxel or Pemetrexed With or Without Cetuximab in Patients With Recurrent or Progressive Non-Small Cell Lung Cancer After Platinum-Based Therapy [NCT00095199] | Phase 3 | 939 participants (Actual) | Interventional | 2005-01-31 | Completed |
| Anlotinib Combined With Docetaxel Versus Docetaxel for Platinum-based Therapy Treated Advanced NSCLC: a Multicentre, Randomised Explorative Trial [NCT03726736] | Phase 1/Phase 2 | 97 participants (Anticipated) | Interventional | 2018-12-21 | Recruiting |
| GALLANT: A Phase 2 Study Using Metronomic Gemcitabine, Doxorubicin, Docetaxel and Nivolumab as Second/Third Line Therapy for Advanced Sarcoma [NCT04535713] | Phase 2 | 260 participants (Anticipated) | Interventional | 2020-09-30 | Recruiting |
| A Randomized, Multicenter, Double-Blind, Placebo-Controlled, Phase III Study to Evaluate Pertuzumab in Combination With Docetaxel and Trastuzumab as Neoadjuvant Therapy, and Pertuzumab in Combination With Trastuzumab as Adjuvant Therapy After Surgery and [NCT02586025] | Phase 3 | 329 participants (Actual) | Interventional | 2016-03-14 | Completed |
| A Phase 2, Multicenter, Randomized Study to Compare the Efficacy and Safety of MK-7684A or MK-7684A Plus Docetaxel Versus Docetaxel Monotherapy in the Treatment of Participants With Metastatic Non-small Cell Lung Cancer With Progressive Disease After Trea [NCT04725188] | Phase 2 | 255 participants (Actual) | Interventional | 2021-04-20 | Active, not recruiting |
| 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 1 | 30 participants (Anticipated) | Interventional | 2021-01-20 | Recruiting |
| UpFrontPSMA : A Randomised Phase 2 Study of Sequential 177Lu-PSMA617 and Docetaxel Versus Docetaxel in Metastatic Hormone-Naive Prostate Cancer [NCT04343885] | Phase 2 | 130 participants (Actual) | Interventional | 2020-04-21 | Active, not recruiting |
| CHAARTED: ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer [NCT00309985] | Phase 3 | 790 participants (Actual) | Interventional | 2006-09-26 | Active, 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 2 | 121 participants (Actual) | Interventional | 2005-09-27 | Active, not recruiting |
| Phase II Trial of Irinotecan/Docetaxel for Advanced Pancreatic Cancer, With Randomization Between Irinotecan/Docetaxel and Irinotecan/Docetaxel Plus C225 a Monoclonal Antibody to the Epidermal Growth Factor Receptor (EGF-r) [NCT00042939] | Phase 2 | 94 participants (Actual) | Interventional | 2003-12-09 | Completed |
| A Phase III, Adjuvant Trial Comparing Three Chemotherapy Regimens in Women With Node-Positive Breast Cancer: Docetaxel/Doxorubicin/Cyclophosphamide (TAC); Dose-Dense (DD) Doxorubicin/Cyclophosphamide Followed By DD Paclitaxel (DD AC→P); DD AC Followed By [NCT00093795] | Phase 3 | 4,894 participants (Actual) | Interventional | 2004-10-31 | Completed |
| An Open-label, Dose-escalation, Safety and Pharmacokinetics Phase I Study of Ombrabulin in Combination With Docetaxel and Cisplatin Every 3 Weeks in Patients With Advanced Solid Tumors [NCT01095302] | Phase 1 | 11 participants (Actual) | Interventional | 2010-05-31 | Completed |
| A Phase III Randomized Trial With NEOadjuvant Chemotherapy (TAC) With or Without ZOledronic Acid for Patients With HER2- Negative Large Resectable or Locally Advanced Breast Cancer(NEO-ZOTAC) [NCT01099436] | Phase 3 | 250 participants (Actual) | Interventional | 2010-04-30 | Completed |
| Phase II Study Of Sequential Gemcitabine Followed By Docetaxel For Recurrent Ewing's Sarcoma, Osteosarcoma, Or Unresectable Or Locally Recurrent Chondrosarcoma [SARC Study] [NCT00073983] | Phase 2 | 54 participants (Actual) | Interventional | 2006-10-31 | Completed |
| A Three-Arm Randomized Trial to Compare Adjuvant Adriamycin and Cyclophosphamide Followed by Taxotere (AC-T); Adriamycin and Taxotere (AT); and Adriamycin, Taxotere, and Cyclophosphamide (ATC) in Breast Cancer Patients With Positive Axillary Lymph Nodes [NCT00003782] | Phase 3 | 5,351 participants (Actual) | Interventional | 1999-03-31 | Completed |
| [NCT02447406] | Phase 1/Phase 2 | 7 participants (Actual) | Interventional | 2015-04-30 | Completed |
| Feasibility Trial of MK3475 + Docetaxel or Gemcitabine in Platinum Pre-treated Urothelial Cancer [NCT02437370] | Phase 1 | 32 participants (Actual) | Interventional | 2015-09-01 | Completed |
| Phase III Trial Assessing the Interest of a Maintenance Chemotherapy Combining Docetaxel (Taxotere) 5-FU After Induction Treatment by Aintensive Chemotherapy for Inflammatory Breast Cancers [NCT02324088] | Phase 3 | 174 participants (Actual) | Interventional | 2000-10-31 | Completed |
| Endostar First-line Treatment of Advanced Non-small Cell Lung Squamous Carcinoma Based on Chemotherapy for Advanced Non-small Cell Lung Squamous Carcinoma Patients：a Randomized Controlled,Open, Multicenter Clinical Study [NCT02513342] | Phase 4 | 400 participants (Anticipated) | Interventional | 2015-03-31 | Recruiting |
| Perioperative Chemotherapy (FLOT Protocol) Compared To Neoadjuvant Chemoradiation (CROSS Protocol) in Patients With Adenocarcinoma of the Esophagus [NCT02509286] | Phase 3 | 438 participants (Actual) | Interventional | 2016-01-31 | Active, not recruiting |
| A Registry Based Study Evaluating Overall Survival and Treatment Length in mCRPC Patients Treated With Enzalutamide in Sweden [NCT03328364] | | 211 participants (Actual) | Observational | 2017-12-01 | Completed |
| A Phase II Trial for the Use of Intravesical Gemcitabine and Docetaxel (GEMDOCE) in the Treatment of BCG naïve Non-muscle Invasive Urothelial Carcinoma of the Bladder [NCT04386746] | Phase 2 | 27 participants (Actual) | Interventional | 2020-07-29 | Active, not recruiting |
| A Randomized, Open-Label Phase 1/2 Study Evaluating Ramucirumab in Pediatric Patients and Young Adults With Relapsed, Recurrent, or Refractory Synovial Sarcoma [NCT04145700] | Phase 1/Phase 2 | 23 participants (Actual) | Interventional | 2020-03-04 | Terminated(stopped due to Study terminated for meeting protocol specified futility criteria.) |
| 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 2 | 6 participants (Actual) | Interventional | 2018-12-19 | Terminated(stopped due to Lack of accrual) |
| Localized High-Risk Soft Tissue Sarcomas Of The Extremities And Trunk Wall In Adults: An Integrating Approach Comprising Standard Vs Histotype-Tailored Neoadjuvant Chemotherapy [NCT01710176] | Phase 3 | 550 participants (Actual) | Interventional | 2011-06-01 | Active, not recruiting |
| A Phase 2 Study to Determine the Efficacy and Safety of BIND-014 (Docetaxel Nanoparticles for Injectable Suspension) in Patients With Urothelial Carcinoma, Cholangiocarcinoma, Cervical Cancer and Squamous Cell Carcinoma of the Head and Neck [NCT02479178] | Phase 2 | 73 participants (Actual) | Interventional | 2015-06-30 | Terminated |
| Phase II Study of Chemo-Radiation-Induced Abscopal Effect in Metastatic Breast Cancer and in Other Metastatic Sites of Solid Tumors [NCT02474186] | Phase 2 | 41 participants (Actual) | Interventional | 2003-04-30 | Completed |
| A Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, Combined With Chemotherapy in Advanced Soft Tissue and Bone Sarcomas [NCT05116800] | Phase 2 | 0 participants (Actual) | Interventional | 2022-03-01 | Withdrawn(stopped due to IND withdrawn) |
| Single Arm, Phase II Clinical Study of Intermittent High Dose of Icotinib in Combination With Docetaxel as Second-line Treatment for Non-small Cell Lung Cancer Patients With Wild Type EGFR: [NCT02191059] | Phase 2 | 60 participants (Anticipated) | Interventional | 2014-07-31 | Not yet recruiting |
| An Open, Single-center, Phase II Trial of Cetuximab+Zimberelimab Combined With Platinum-containing Dual-agent Neoadjuvant Therapy for Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT06107114] | Phase 2 | 52 participants (Anticipated) | Interventional | 2023-12-01 | Not yet recruiting |
| Neoadjuvant Toripalimab and Albumin Paclitaxel /Cisplatin Versus Docetaxel/ Cisplatin/ 5-fluorouracil (TPF) on Pathological Response in Patients With Locally Advanced and Resectable Oral Squamous Cell Carcinoma [NCT05125055] | Phase 2/Phase 3 | 80 participants (Anticipated) | Interventional | 2021-10-01 | Recruiting |
| A Pilot Trial of Cisplatin/Etoposide/Radiotherapy Followed by Consolidation Docetaxel and the Addition of Bevacizumab (NSC-704865) in Three Cohorts of Patients With Inoperable Locally Advanced Stage III Non-small Cell Lung Cancer [NCT00334815] | Phase 2 | 29 participants (Actual) | Interventional | 2006-06-15 | Active, not recruiting |
| A Randomized Multicenter Phase III Trial Comparing Docetaxel or Hormone Therapy as Second Line Treatment in Patients With Asymptomatic or Oligosymptomatic Metastatic Castration-resistent Prostate Cancer (mCRPC) Progressing After Abiraterone or Enzalutamid [NCT04139772] | Phase 3 | 18 participants (Actual) | Interventional | 2019-09-01 | Active, not recruiting |
| Adjuvant Dynamic Marker-Adjusted Personalized Therapy Trial Optimizing Risk Assessment and Therapy Response Prediction in Early Breast Cancer [NCT01779206] | Phase 2/Phase 3 | 4,936 participants (Anticipated) | Interventional | 2012-05-31 | Active, not recruiting |
| A Phase II Trial of Neoadjuvant Nivolumab, Docetaxel, Cisplatin Therapy Followed by Surgery and Radiation Therapy for Resectable High Grade Salivary Gland Carcinoma [NCT05727410] | Phase 2 | 50 participants (Anticipated) | Interventional | 2022-11-15 | Recruiting |
| 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 2 | 178 participants (Anticipated) | Interventional | 2021-06-24 | Recruiting |
| A Phase II, Single-center, Open-label, Single-arm Study of Induction Chemotherapy Combined With Immunotherapy for Locally Advanced Hypopharyngeal Carcinoma [NCT04156698] | Phase 2 | 51 participants (Anticipated) | Interventional | 2020-05-21 | Active, not recruiting |
| An Open-label Phase Ib/II Study of BAY 1000394 (Roniciclib) in Combination With Docetaxel in Second- or Third-line Treatment of Patients With Advanced Non-small Cell Lung Cancer (NSCLC) [NCT02522910] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2015-08-31 | Withdrawn |
| A Phase III, Randomized, Double-blind, Placebo-controlled Multi-center Study of ASA404 in Combination With Docetaxel in Second-line Treatment of Patients With Locally Advanced or Metastatic (Stage IIIb/IV) Non-small Cell Lung Cancer (NSCLC) [NCT00738387] | Phase 3 | 900 participants (Actual) | Interventional | 2008-12-31 | Terminated |
| The Prognosis Study of Postoperative Non-small-cell Lung Cancer Patients Treated Precisely With the Integrated Traditional Chinese and Western Medicine Based on CTC Detection [NCT03269162] | Phase 3 | 144 participants (Anticipated) | Interventional | 2016-09-30 | Active, not recruiting |
| Phase II, Single-arm Study of Selumetinib in Combination With Docetaxel, in Advanced Gastric Adenocarcinoma Patients With Low/High MEK Signature, RAS Mutation or RAS Amplification as a Second-line Chemotherapy [NCT02448290] | Phase 2 | 25 participants (Actual) | Interventional | 2014-11-12 | Completed |
| Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Docetaxel for Injection (Albumin-bound) in Different Dose Regimens in Patients With Advanced Solid Tumors: An Open-label, Multicenter, Phase 1b Study [NCT05114915] | Phase 1 | 144 participants (Anticipated) | Interventional | 2022-01-07 | Recruiting |
| A Prospective, Open-label, Randomized Controlled Clinical Study of Apatinib Combined With Docetaxel in the Treatment of Advanced Esophageal Squamous Cell Carcinoma [NCT03193424] | Phase 2 | 120 participants (Anticipated) | Interventional | 2016-10-31 | Recruiting |
| Phase III Randomized Comparing Docetaxel, Doxorubicin and Cyclophosphamide (TAC) vs 5-Fluorouracil, Doxorubicin and Cyclophosphamide (FAC) as Adjuvant Treatment of High Risk Operable Breast Cancer Patients With Negative Axillary Lymph Nodes [NCT00121992] | Phase 3 | 1,060 participants (Actual) | Interventional | 1999-07-31 | Completed |
| Observational Study of Metastatic Prostate Cancer Subjects Receiving Docetaxel Therapy for Evaluation of Docetaxel Plasma Levels Using the MyDocetaxel Assay [NCT02376296] | | 35 participants (Actual) | Observational | 2015-02-28 | Completed |
| Docetaxel Plus Famitinib Versus Docetaxel Plus Placebo in Patients With Advanced Non-squamous and Non-Small Cell Lung Cancer (NSCLC) [NCT02364362] | Phase 1 | 18 participants (Actual) | Interventional | 2015-01-31 | Completed |
| An Open-label, Randomized Clinical Trial of Recombinant Human Endostatin (Endo) Combined With Chemotherapy Compared With Chemotherapy for Adjuvant Treatment of Esophageal Cancer [NCT03649945] | Phase 2 | 186 participants (Anticipated) | Interventional | 2018-11-30 | Not yet recruiting |
| Phase I/II Study With the Combination of Dacomitinib and PD-0325901 in Metastatic KRAS Mutation Positive Non-small Cell Lung Cancer [NCT02039336] | Phase 1/Phase 2 | 35 participants (Anticipated) | Interventional | 2014-01-31 | Recruiting |
| Phase I Study To Determine The Maximally Tolerated Dose Of Oral, Daily CP-868,596 And CP-868,596 Plus AG-013736 When Given In Combination With Docetaxel Administered Every 3 Weeks To Patients With Advanced Solid Tumors [NCT00949624] | Phase 1 | 50 participants (Actual) | Interventional | 2005-12-31 | Completed |
| Sequential Chemoradiotherapy With Reduced Target Delineation and Radiation Doses During Radiotherapy for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma [NCT03389295] | Phase 2 | 118 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Phase I Study - Hypofractionated Cyberknife Radiotherapy Combined With Neoadjuvant Chemotherapy for Breast Tumors [NCT00872625] | Phase 1 | 26 participants (Actual) | Interventional | 2007-04-30 | Completed |
| A Multicentre Phase IIa Study to Evaluate the Efficacy and Tolerability of ModraDoc006/r in Patients With Recurrent or Metastatic HER-2 Negative Breast Cancer, Suitable for Treatment With a Taxane [NCT03890744] | Phase 2 | 12 participants (Actual) | Interventional | 2019-01-30 | Completed |
| Multicenter Safety, Feasibility and Pharmacokinetic Phase I Trial of ModraDoc006/r in Patients With Metastatic Castration-resistant Prostate Cancer [NCT03136640] | Phase 1 | 23 participants (Actual) | Interventional | 2017-04-26 | Completed |
| A Multicenter, Phase II, Open Label, Randomized Trial Evaluating the Efficacy of Tedopi Plus Docetaxel or Tedopi Plus Nivolumab as Second-line Therapy in Metastatic Non-small-cell Lung Cancer Progressing After First-line Chemo-immunotherapy (Combi-TED) [NCT04884282] | Phase 2 | 105 participants (Anticipated) | Interventional | 2021-10-12 | Recruiting |
| An Open, Single-arm and Multi-center Pharmacokinetic Study of Pyrotinib and Docetaxel Plus Trastuzumab in Patients With HER2 Positive Recurrent or Metastasis Breast Cancer. [NCT04367090] | Phase 1 | 97 participants (Actual) | Interventional | 2020-05-28 | Completed |
| Phase II Study of Docetaxel Chemotherapy With Pembrolizumab and Interleukin-12 Gene Therapy in Patients With Anthracycline- Refractory Triple Negative Breast Cancer (INTEGRAL) [NCT04095689] | Phase 2 | 30 participants (Anticipated) | Interventional | 2021-03-17 | Suspended(stopped due to Stopping rules met per protocol, comprehensive review needed prior to enrolling again) |
| Taxotere Plus Concurrent Concomitant Boost Radiotherapy For Squamous Cell Cancer of the Head and Neck (TAXT-XRT) [NCT00006107] | Phase 1 | 31 participants (Actual) | Interventional | 2000-07-14 | Completed |
| A Phase III Randomized Trial of MK-3475 (Pembrolizumab) Versus Standard Treatment in Subjects With Recurrent or Metastatic Head and Neck Cancer [NCT02252042] | Phase 3 | 495 participants (Actual) | Interventional | 2014-11-17 | Completed |
| An Open-Label, Randomized, Cross-Over, Multicenter, Phase IIIb Study, to Assess Patients' Tolerability of Trastuzumab Administrated Subcutaneously (SC) Either Via a Single Use Injection Device (SID) or Via Vial for Manual Administration (SC Vial) in Patie [NCT02194166] | Phase 3 | 90 participants (Actual) | Interventional | 2014-07-18 | Completed |
| Phase I Open-Label, Dose Escalation Study To Determine The Maximum Tolerated Dose And To Evaluate The Safety Profile of Lenalidomide (Revlimid® CC-5013) With Every Three Week Docetaxel (Taxotere®) In Subjects With Androgen Independent Prostate Cancer [NCT01378091] | Phase 1 | 64 participants (Actual) | Interventional | 2005-08-31 | Completed |
| A Phase II Trial to Assess the Efficacy and Safety of Panitumumab Combined With Docetaxel and Cisplatin as a First-line Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma [NCT01379807] | Phase 2 | 55 participants (Anticipated) | Interventional | 2010-12-31 | Active, not recruiting |
| A Randomized Phase III Study Of Low-Docetaxel Oxaliplatin, Capecitabine (Low-Tox) Vs Epirubicin, Oxaliplatin And Capecitabine (Eox) In Patients With Locally Advanced Unresectable Or Metastatic Gastric Cancer [NCT02076594] | Phase 3 | 171 participants (Actual) | Interventional | 2013-01-31 | Terminated(stopped due to The interim analysis performed on 09 November 2018, showed the failure to achieve the primary objective of effectiveness of the experimental treatment.) |
| A Phase I Study Using Low-Dose Fractionated Whole Abdominal Radiation Therapy (LDFWART) As A Docetaxel Chemo-Potentiator for Patients With Platinum-Resistant Recurrent Ovarian Carcinoma [NCT02083536] | Phase 1 | 0 participants (Actual) | Interventional | 2014-05-31 | Withdrawn(stopped due to Study voluntarily stopped by Principal Investigator due to lack of accrual.) |
| [NCT02223884] | Phase 2 | 30 participants (Actual) | Interventional | 2011-07-31 | Completed |
| A Randomized Phase III Study of Docetaxel/ Epirubicin Versus Tailored Regimens as Neoadjuvant Chemotherapy for Stage II/III Breast Cancer With Tumor Size More Than 2 cm [NCT00776724] | Phase 3 | 166 participants (Actual) | Interventional | 2008-05-29 | Completed |
| A Randomized, Open-label Phase 2 Study of EC145 Single-agent and the Combination of EC145 Plus Docetaxel Versus Docetaxel Alone in Participants With Folate-receptor Positive [FR(++)] Second Line NSCLC [NCT01577654] | Phase 2 | 203 participants (Actual) | Interventional | 2011-03-31 | Completed |
| Pegylated Liposomal Doxorubicin (Caelyx) in Combination With Herceptin and Taxotere as First-line Chemotherapy in Metastatic Breast Cancer Patients: A 2 Stage Phase II, Open Label, Multicenter Study. [NCT00687440] | Phase 2 | 27 participants (Actual) | Interventional | 2005-07-15 | Completed |
| Three Drugs in Advanced Gastric Cancer Neoadjuvant Chemotherapy for Stage Ⅲ Multicenter, Open, Randomized, Controlled Clinical Study [NCT02555358] | Phase 2 | 300 participants (Actual) | Interventional | 2014-11-30 | Completed |
| Phase II Study of Preoperative TPF Chemotherapy in Locally Advanced Resectable Oral Cavity Squamous Cell Cancer in Order to Improve the Rate of Pathological Complete Response [NCT01914900] | Phase 2 | 14 participants (Actual) | Interventional | 2012-06-30 | Completed |
| 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 2 | 20 participants (Actual) | Interventional | 2009-11-30 | Completed |
| Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Albumin-bound Formulation of Docetaxel for Intravenous Infusion in Patients With Advanced Solid Tumors: A Phase 1, Single-center, Open-label, Dose-escalation Study [NCT04471675] | Phase 1 | 208 participants (Anticipated) | Interventional | 2020-12-02 | Recruiting |
| 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 3 | 800 participants (Anticipated) | Interventional | 2021-11-11 | Not yet recruiting |
| An Open Label, Multicenter, Phase 2 Study to Determine the Safety and Efficacy of BIND-014 (Docetaxel Nanoparticles for Injectable Suspension) as a Second-Line Therapy for Patients With KRAS Mutation Positive or Squamous Cell Non-Small Cell Lung Cancer [NCT02283320] | Phase 2 | 69 participants (Actual) | Interventional | 2014-09-30 | Completed |
| 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 2 | 2 participants (Actual) | Interventional | 2016-11-30 | Terminated(stopped due to Competing studies) |
| A Phase I Pilot Study of SBRT and Concurrent Docetaxel for Reirradiation of Locally Recurrent or Second Primary Squamous Cell Carcinoma of the Head and Neck [NCT02110992] | Phase 1 | 7 participants (Actual) | Interventional | 2014-04-30 | Terminated(stopped due to slow accrual) |
| Anlotinib Plus Docetaxel Versus Docetaxel for Treatment of EGFR/ALK/ROS1 Mutation-negative Advanced Nonsquamous NSCLC After Disease Progression on Platinum-based Therapy : a Multicentre, Double-blind, Randomised Explorative Trial [NCT03654027] | Phase 2 | 84 participants (Anticipated) | Interventional | 2018-10-01 | Not yet recruiting |
| Adjuvant Chemotherapy of Breast Cancer: Sequential Chemotherapy vs. Standard Therapy. Prospective Randomised Comparison of 4 x Epirubicin and Cyclophosphamide (EC) --> 4 x Docetaxel (Doc) vs. 6 x CMF / CEF in Patients With 1 to 3 Positive Lymph Nodes [NCT02115204] | Phase 3 | 2,011 participants (Actual) | Interventional | 2000-06-30 | Completed |
| A Phase II Clinical Trial Evaluating the Safety and Efficacy of Combination of Hyperthermia and Concurrent Chemoradiotherapy (CCRT) in Treatment Failure Solid Tumors [NCT02120118] | Phase 2 | 0 participants (Actual) | Interventional | 2014-02-28 | Withdrawn(stopped due to Taiwan FDA asked for seperating this protocol into one disease site per protocol.) |
| Assessment of the Clinical Value of a Docetaxel, Cisplatin and 5-fluorouracil (DCF) Strategy Adapted to Patients for the Management of Metastatic or Locally Advanced Anal Resistant Radiochemotherapy Squamous Cell Anal Carcinoma. [NCT02402842] | Phase 2 | 70 participants (Actual) | Interventional | 2014-09-30 | Completed |
| A Multicenter, Randomized, Controlled Phase II Clinical Study of Comparison of Docetaxel for Injection (Albumin-bound) and Taxotere in Second-line or Above Locally Advanced or Metastatic Gastric Adenocarcinoma or Gastroesophageal Junction Adenocarcinoma [NCT05705635] | Phase 2 | 100 participants (Anticipated) | Interventional | 2023-01-13 | Recruiting |
| A Randomized, Double-blind, Placebo Controlled Phase III Study of Darolutamide (ODM-201) Versus Placebo in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Patients With Metastatic Hormone Sensitive Prostate Cancer [NCT02799602] | Phase 3 | 1,306 participants (Actual) | Interventional | 2016-11-30 | Completed |
| The Function of Pre-Albumin, Retinol Conjugated Protein and Transferrin in Early Malnutrition Detecting and Nutritional Status Dynamic Monitoring for Local Advanced Nasopharyngeal Carcinoma Patients With Chemoradiotherapy [NCT03240835] | | 50 participants (Anticipated) | Observational | 2017-09-12 | Active, not recruiting |
| Response Adapted Neoadjuvant Therapy in Gastroesophageal Cancers (RANT-GC Trial) - a Phase Ib Feasibility Trial [NCT05733689] | Phase 1 | 20 participants (Anticipated) | Interventional | 2023-12-31 | Not yet recruiting |
| Randomised Phase III Study of Docetaxel vs Active Symptom Control in Patients With Relapsed Oesophago-gastric Adenocarcinoma [NCT00978549] | Phase 3 | 320 participants (Anticipated) | Interventional | 2008-04-30 | Completed |
| Phase II Study of Neo-adjuvant Chemotherapy With Letrozole in Patients With Estrogen Receptor Positive/HER-2 Negative Breast Cancer [NCT03497702] | Phase 2 | 114 participants (Anticipated) | Interventional | 2017-05-08 | Recruiting |
| 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 2 | 7 participants (Actual) | Interventional | 2007-11-30 | Completed |
| 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 1 | 15 participants (Anticipated) | Interventional | 2021-09-30 | Not yet recruiting |
| Clarify of Predictive Risk Factors of Chemotherapy-induced Liver Injury After Therapy With Docetaxel and Cisplatin for Nasopharyngeal Carcinoma [NCT03069820] | Phase 4 | 120 participants (Anticipated) | Interventional | 2017-02-10 | Recruiting |
| Neoadjuvant TIL- and Response-Adapted Chemoimmunotherapy for TNBC [NCT05645380] | Phase 2 | 139 participants (Anticipated) | Interventional | 2022-12-05 | Recruiting |
| Open-Label, Global, Multicenter, Randomized, Phase 3 Study of Sacituzumab Govitecan Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) With Progression on or After Platinum-Based Chemotherapy and Anti-PD-1/PD-L1 Im [NCT05089734] | Phase 3 | 580 participants (Anticipated) | Interventional | 2021-11-17 | Active, not recruiting |
| A Phase II Study of Duvelisib Plus Docetaxel in PD-1 Inhibitor Experienced Patients With Incurable Head and Neck Squamous Cell Carcinoma [NCT05057247] | Phase 2 | 26 participants (Actual) | Interventional | 2021-10-14 | Active, 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 2 | 86 participants (Actual) | Interventional | 2015-01-31 | Active, not recruiting |
| A Randomized Phase Ⅱ/Ⅲ Trial of Postoperative Concurrent Chemoradiotherapy Versus Radiotherapy Alone for Patients With Locoregionally Advanced Esophageal Squamous Cell Carcinoma [NCT03600831] | Phase 2/Phase 3 | 434 participants (Anticipated) | Interventional | 2018-08-20 | Recruiting |
| A Phase I/II Clinical Trial of Sorafenib in Combination With Cisplatin and Docetaxel in Patients With Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT02035527] | Phase 1 | 3 participants (Actual) | Interventional | 2014-04-14 | Completed |
| A Phase I Open-label Dose Escalation Study of Single Oral Daily Doses of BIBW 2992 for Three Days After Administration of Docetaxel, in Patients With Advanced Solid Tumors [NCT02171676] | Phase 1 | 40 participants (Actual) | Interventional | 2005-05-31 | Completed |
| [NCT03067792] | Phase 3 | 52 participants (Actual) | Interventional | 2014-12-31 | Completed |
| Weekly ModraDoc/r in Combination With Hormonal Treatment and High-dose Intensity-modulated Radiation Therapy in Patients With High-risk Early Stage Prostate Cancer [NCT03066154] | Phase 1 | 24 participants (Anticipated) | Interventional | 2016-09-30 | Recruiting |
| Phase II Study of Taxotere® (Docetaxel) + ZD1839 (IRESSA®) in Previously Untreated Elderly Patients (≥70 Years Old) With Stage III-b (With Malignant Pleural Effusion [MPE+]) or Stage IV Non-Small Cell Lung Cancer (NSCLC) [NCT00231465] | Phase 2 | 44 participants (Actual) | Interventional | 2003-07-31 | Completed |
| Phase 1/2 Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin and Irinotecan in Subjects With Metastatic Pancreatic Cancer [NCT02324543] | Phase 1/Phase 2 | 47 participants (Actual) | Interventional | 2015-02-28 | Completed |
| A Randomized, Open Labeled Phase II Pilot Study of Total Neoadjuvant Chemotherapy With FLOT ( FLOT-TNT) VS Standard Perioperative FLOT ( FLOTPOP) in Patients With Gastric or GEJ Cancer, and Assessment of CTDNA as Correlative Biological Response [NCT05567835] | Phase 2 | 50 participants (Anticipated) | Interventional | 2023-12-31 | Not yet recruiting |
| A Phase 2 Study of 9-ING-41, a Glycogen Synthase Kinase-3 Beta (GSK-3β) Inhibitor, Combined With Chemotherapy in Adolescents and Adults With Advanced Sarcomas [NCT04906876] | Phase 2 | 0 participants (Actual) | Interventional | 2021-09-30 | Withdrawn(stopped due to IND withdrawn) |
| An Open-Label, Randomized Phase II Study of Herceptin (Trastuzumab), Taxotere (Docetaxel), and Xeloda (Capecitabine) in Combination, Versus Herceptin (Trastuzumab) Plus Taxotere (Docetaxel), in Patients With Advanced and/or Metastatic Breast Cancers That [NCT02748213] | Phase 2 | 225 participants (Actual) | Interventional | 2002-02-28 | Completed |
| A Non-comparative Randomized 2:1 Phase II Study of Docetaxel, Cisplatin, and 5-fluorouracil in Combination or Not With Atezolizumab in Patients With Metastatic or Unresectable Locally Advanced Squamous Cell Anal Carcinoma [NCT03519295] | Phase 2 | 99 participants (Anticipated) | Interventional | 2018-07-22 | Active, not recruiting |
| Dose Reduction of Docetaxel-Based Chemotherapy in Vulnerable Older Women With Early-Stage Breast Cancer (DOROTHY) [NCT06042569] | Phase 2 | 174 participants (Anticipated) | Interventional | 2023-12-28 | Recruiting |
| Phase I Trial Study of Gemcitabine and Docetaxel With Radiation in Adult Patients With High Grade and Greater Than 5 cm Soft Tissue Sarcoma of the Extremities [NCT04037527] | Phase 1 | 27 participants (Anticipated) | Interventional | 2020-08-18 | Recruiting |
| 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 2 | 75 participants (Actual) | Interventional | 2018-11-20 | Completed |
| A Randomized Phase II Study to Assess the Activity of TroVax® (MVA-5T4) Plus Docetaxel Versus Docetaxel Alone in Subjects With Progressive Hormone Refractory Prostate Cancer [NCT01194960] | Phase 2 | 25 participants (Actual) | Interventional | 2010-08-31 | Terminated |
| A Phase II, Multicenter, Open-Label, Randomized Study of YM155 Plus Docetaxel as First-Line Treatment in Subjects With HER2 Negative Metastatic Breast Cancer [NCT01038804] | Phase 2 | 101 participants (Actual) | Interventional | 2009-12-31 | Completed |
| The Prospective,Multicenter,Randomized Controlled Clinical Study of the Optimal Intervention Time of Radiotherapy for Oligometastatic Stage IV Non-small Cell Lung Cancer（NSCLC） [NCT02076477] | Phase 3 | 420 participants (Anticipated) | Interventional | 2014-01-31 | Recruiting |
| A Randomized Multicenter Phase II Trial of Patupilone (EPO906) Plus Prednisone Versus Docetaxel Plus Prednisone in Patients With Metastatic Hormone Refractory Prostate Cancer [NCT00411528] | Phase 2 | 185 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Phase II Evaluation of Adjuvant Hyperfractionated Radiation and Docetaxel for HPV Associated Oropharynx Cancer [NCT01932697] | Phase 2 | 81 participants (Actual) | Interventional | 2013-09-04 | Completed |
| A Phase 2 Study of Pembrolizumab in Combination With Plinabulin and Docetaxel in Previously Treated Patients With Metastatic Non-Small Cell Lung Cancer and Progressive Disease (PD) After Immunotherapy (Anti-PD-1/PD-L1 Inhibitor) Alone or in Combination Wi [NCT05599789] | Phase 2 | 47 participants (Anticipated) | Interventional | 2023-02-01 | Recruiting |
| [NCT01648517] | Phase 2 | 60 participants (Actual) | Interventional | 2012-07-27 | Completed |
| A Phase III Randomized Study of Primary Chemotherapy With Adriamycin/Cyclophosphamide(AC) vs Taxotere/Xeloda(TX) for Stage II and III Breast Cancer [NCT00352378] | Phase 3 | 209 participants (Actual) | Interventional | 2002-06-30 | Completed |
| STAMPEDE: Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: A Multi-Stage Multi-Arm Randomised Controlled Trial [NCT00268476] | Phase 2/Phase 3 | 11,992 participants (Actual) | Interventional | 2005-07-08 | Active, not recruiting |
| Phase II Study of Neoadjuvant Hormonal Therapy Plus Docetaxel Followed by Radical Prostatectomy for Men With Proven or Suspected Node-positive Prostate Cancer [NCT01076335] | Phase 2 | 40 participants (Actual) | Interventional | 2005-05-31 | Completed |
| Phase I/II Trial Of Weekly Irinotecan And Docetaxel With The Addition Of Celecoxib In Advanced Non-Small Cell Lung Cancer [NCT00073866] | Phase 1/Phase 2 | 0 participants | Interventional | 2003-06-30 | Completed |
| A Prospective Single-center Randomized Phase 2 Trial Comparing Docetaxel Plus Fulvestrant With Docetaxel in Postmenopausal, Hormone-receptor Positive and HER2-negative Metastatic Breast Cancer [NCT02137083] | Phase 2 | 22 participants (Actual) | Interventional | 2014-04-30 | Completed |
| A Phase Ib, Open-label Study of Safety and Pharmacokinetics of Volitinib in Combination With Docetaxel in Patients With Advanced Gastric Cancer [NCT02252913] | Phase 1 | 25 participants (Actual) | Interventional | 2014-09-30 | Completed |
| Dose-dense Biweekly Docetaxel, Oxaliplatin and 5-fluorouracil as First-line Treatment in Advanced Gastric Cancer [NCT02289378] | Phase 2 | 30 participants (Anticipated) | Interventional | 2014-11-30 | Recruiting |
| A Phase Ia/Ib, First-in-human, Open Label, Multicentre, Dose-escalation and Dose-expansion Study of a Novel NanoZolid®-Docetaxel Depot Formulation (NZ-DTX Depot) Given as an Intra-tumoural Injection in Patients With Advanced Solid Tumours [NCT04810208] | Phase 1 | 6 participants (Actual) | Interventional | 2019-02-28 | Terminated(stopped due to Strategic decision) |
| 12 weekS Adjuvant dOcetaxel Plus trastuzumaB in Patients With Tumors ≤1cm, Node-negative, HER2-positive Breast cancER (SOBER):a Single-grouparm, Open-label, Prospective, Phase 2 Study [NCT03367676] | Phase 2 | 112 participants (Anticipated) | Interventional | 2017-12-30 | Recruiting |
| The Evaluation of First-line Treatment Efficacy of Docetaxel and Abiraterone in Metastatic Castration-resistant Prostate Cancer Patients With Intraductal Carcinoma of the Prostate and the Exploration of the Genes Related to Treatment Effect [NCT03356444] | Phase 2 | 140 participants (Anticipated) | Interventional | 2017-11-30 | Not yet recruiting |
| Nedaplatin Versus Cisplatin and Capecitabine Versus Fluorouracil in Induction Chemotherapy Plus Concurrent Chemoradiotherapy for Locoregionally Advanced NPC： a Phase 3, Multicentre, Non-inferiority, Randomised Factorial Trial [NCT03503136] | Phase 3 | 632 participants (Anticipated) | Interventional | 2018-06-30 | Not yet recruiting |
| A Pilot Study Targeting Angiogenesis Using Bevacizumab Combined With Chemotherapy and Histone Deacetylase Inhibitor (Valproic Acid) in Advanced Sarcomas [NCT01106872] | Phase 1 | 47 participants (Actual) | Interventional | 2010-09-30 | Completed |
| Phase I/II Study of Split-dose TPF-Induction Chemotherapy Before Surgery of Oropharyngeal and Cavity of the Mouth Cancer [NCT01108042] | Phase 1/Phase 2 | 71 participants (Actual) | Interventional | 2009-11-30 | Completed |
| Phase III Clinical Study of PD-1 Monoclonal Antibody-activated Autologous Peripheral Blood T-Lymphocyte (PD1-T) Combined With Docetaxel in the Second-line Treatment of IIIB/IIIC/IV Non-small Cell Lung Cancer [NCT03944980] | Phase 3 | 146 participants (Anticipated) | Interventional | 2019-06-01 | Recruiting |
| A Pilot Study of Induction Chemotherapy Followed by Surgery for Locally Advanced Resectable Head and Neck Cancer [NCT01111942] | Early Phase 1 | 4 participants (Actual) | Interventional | 2010-02-28 | Terminated(stopped due to lack of enrollment) |
| Multicenter Randomized Phase II Study for the Therapy of Locally Advanced or Metastatic NSCLC (Stage IIIB/IV) With Cisplatin/Docetaxel or Oxaliplatin/Docetaxel [NCT01222312] | Phase 2 | 88 participants (Actual) | Interventional | 2008-08-31 | Completed |
| Endostar Continuous Intravenous Infusion Combined With Induction Chemotherapy and Concurrent Chemoradiotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma (NPC). [NCT03932266] | Phase 2 | 73 participants (Anticipated) | Interventional | 2019-06-30 | Not yet recruiting |
| A Randomized Phase III Study to Investigate the Efficacy and Safety of Docetaxel + Capecitabine vs. Vinorelbine + Capecitabine Followed by Capecitabine Alone as 1st Therapy on Locally Advanced and Metastatic Breast Cancer Patients. [NCT01126138] | Phase 3 | 200 participants (Anticipated) | Interventional | 2010-07-31 | Recruiting |
| A Phase II, Randomized, Open-label Study of Lapatinib Plus Chemotherapy Versus Trastuzumab Plus Chemotherapy as First-line Treatment for Women With HER2-positive and p95HER2-positive Metastatic Breast Cancer [NCT01137994] | Phase 2 | 0 participants (Actual) | Interventional | 2011-10-31 | Withdrawn |
| A Phase II Study Of The Weekly Administration Of Docetaxel In Combination With The Epidermal Growth Factor Receptor Inhibitor OSI-774 In Recurrent And/Or Metastatic Breast Cancer [NCT00054275] | Phase 2 | 39 participants (Actual) | Interventional | 2002-12-31 | Completed |
| ARTemis - Avastin Randomized Trial With Neo-Adjuvant Chemotherapy for Patients With Early Breast Cancer [NCT01093235] | Phase 3 | 800 participants (Anticipated) | Interventional | 2009-04-30 | Recruiting |
| An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Advanced or Metastatic Squamous Cell Non-small Cell Lung Cancer (NSCLC) [NCT01642004] | Phase 3 | 272 participants (Actual) | Interventional | 2012-10-16 | Completed |
| A Trial to Determine the Maximum Tolerated Dose and Evaluate the Safety and Pharmacokinetics of Docetaxel-PNP, Polymeric Nanoparticle Formulation of Docetaxel, in Subjects With Advanced Solid Malignancies [NCT01103791] | Phase 1 | 19 participants (Actual) | Interventional | 2010-04-30 | Completed |
| Phase I Study of Ceritinib Plus Docetaxel in ALK-Negative, EGFR WT Advanced NSCLC [NCT03611738] | Phase 1 | 21 participants (Actual) | Interventional | 2019-02-01 | Active, not recruiting |
| 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 4 | 10 participants (Anticipated) | Interventional | 2014-10-31 | Active, not recruiting |
| An Investigator-Sponsored Phase 1/2 Study of Selinexor (KPT-330) and Docetaxel as Second Line Therapy in Patients With Relapsed Squamous Cell Lung Cancer [NCT02536495] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2015-09-30 | Withdrawn(stopped due to PI decision due to funding support) |
| A Phase 2, Randomized, 2-Arm, Double-Blind Study of AT-101 in Combination With Docetaxel Versus Docetaxel Plus Placebo in Patients With Relapsed or Refractory Non-Small Cell Lung Cancer (NSCLC) [NCT00544960] | Phase 2 | 106 participants (Actual) | Interventional | 2007-09-30 | Completed |
| A Multi-Center, Randomized Phase III Study of Neoadjuvant Anti-PD-1 Immunotherapy Plus TP Chemotherapy Versus TP Chemotherapy or Up-Front Surgery in Resectable Locally Advanced Oral Squamous Cell Carcinoma [NCT05798793] | Phase 3 | 309 participants (Anticipated) | Interventional | 2023-11-20 | Not yet recruiting |
| A Multicenter, Open-label, Phase 2 Study to Evaluate the Efficacy and Safety of SKB264 Monotherapy in Selected Subjects With Advanced Solid Tumors [NCT05631262] | Phase 2 | 366 participants (Anticipated) | Interventional | 2022-11-30 | Recruiting |
| A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C [NCT04303780] | Phase 3 | 345 participants (Actual) | Interventional | 2020-06-04 | Active, not recruiting |
| A Randomized Phase 3 Study of Sitravatinib in Combination With Nivolumab Versus Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer With Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy S [NCT03906071] | Phase 3 | 532 participants (Anticipated) | Interventional | 2019-07-15 | Active, not recruiting |
| A Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, Compared With Placebo in Combination With Docetaxel, in Patients Receiving [NCT01750281] | Phase 2 | 212 participants (Actual) | Interventional | 2012-12-18 | Completed |
| A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Paclitaxel With or Without Bevacizumab for the Treatment of Platinum-resistant Recurrent Ovarian Cancer (KEYNOTE-B96/ENGOT-ov65) [NCT05116189] | Phase 3 | 616 participants (Anticipated) | Interventional | 2021-12-13 | Active, not recruiting |
| A Prospective， Randomized， Open-label， Multicentric，phaseIII Clinical Trial Compared With PC and CEF100 Followed by Docetaxel as Adjuvant Chemotherapy Regimen for Chinese Primary Triple Negative Breast Cancer Patients [NCT01216111] | Phase 3 | 647 participants (Actual) | Interventional | 2011-01-01 | Completed |
| 替雷利珠单抗联合含铂双药新辅助治疗用于提高可切除局部晚期口腔鳞癌下颌骨保留的前瞻性、单臂Ⅱ期临床试验 [NCT06130007] | Phase 2 | 48 participants (Anticipated) | Interventional | 2023-11-25 | Not yet recruiting |
| A Phase 1b Trial Investigating Docetaxel Combined With Cirmtuzumab in Patients With Metastatic Castration Resistant Prostate Cancer [NCT05156905] | Phase 1 | 32 participants (Anticipated) | Interventional | 2022-06-16 | Recruiting |
| A Global, Multicenter, Three Arms, Open-label Randomized Study to Evaluate the Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension Compared to Taxotere® (Docetaxel Injection Concentrate) in Triple-negative Breast Cancer Patients With Locally Advan [NCT03671044] | Phase 3 | 657 participants (Anticipated) | Interventional | 2018-07-10 | Recruiting |
| A Randomised Non-comparative Phase II Trial of Biomarker-driven Intermittent Docetaxel Versus Standard-of-care (SOC) Docetaxel in Metastatic Castration-resistant Prostate Cancer (mCRPC) [NCT04918810] | Phase 2 | 120 participants (Anticipated) | Interventional | 2021-11-11 | Recruiting |
| Randomized, Double-blind, Parallel Controlled, Multicenter Phase II Clinical Trial to Evaluate the Safety and Efficacy of TQB2450 Injection Combined With Arotinib Capsules and Chemotherapy in the Treatment of Advanced Non-small Cell Lung Cancer After Immu [NCT06141226] | Phase 2 | 148 participants (Anticipated) | Interventional | 2023-04-12 | Recruiting |
| A Phase 1b Study to Evaluate HMBD-001 With or Without Chemotherapy in Participants With Advanced Solid Tumors Harboring NRG1 Gene Fusions or Selected HER3 Mutations [NCT05919537] | Phase 1 | 68 participants (Anticipated) | Interventional | 2023-09-06 | Recruiting |
| A Phase 1b Study to Evaluate HMBD-001 in Combination With Docetaxel With or Without Cetuximab in Participants With Advanced Squamous Non-small Cell Lung Cancers [NCT05910827] | Phase 1/Phase 2 | 62 participants (Anticipated) | Interventional | 2023-12-31 | Recruiting |
| A Randomized Phase II Study of 177 LuPSMA-617 vs Docetaxel in Patients With Metastatic Castration-Resistant Prostate Cancer and PSMA-Positive Disease [NCT04663997] | Phase 2 | 200 participants (Anticipated) | Interventional | 2021-08-11 | Recruiting |
| 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 3 | 990 participants (Anticipated) | Interventional | 2021-01-10 | Active, not recruiting |
| A Phase III Randomized Trial of Adjuvant Chemotherapy With or Without Bevacizumab for Patients With Completely Resected Stage IB (≥ 4 cm) - IIIA Non-small Cell Lung Cancer (NSCLC) [NCT00324805] | Phase 3 | 1,501 participants (Actual) | Interventional | 2007-06-01 | Active, not recruiting |
| A Pilot Study of Customizing First Line Chemotherapy in Advanced Non-Small Cell Lung Cancer Based on Molecular Markers [NCT01356368] | Phase 2 | 3 participants (Actual) | Interventional | 2010-05-31 | Terminated(stopped due to slow accrual rate) |
| Multicenter Phase II Study of Docetaxel and Oxaliplatin Combination in Patients With Locally Advanced or Metastatic Biliary Tract Cancer [NCT01234051] | Phase 2 | 53 participants (Anticipated) | Interventional | 2010-11-30 | Recruiting |
| A Phase Ib, Open-label, Dose-escalation Study of the Safety and Pharmacology of Ipatasertib (GDC-0068) in Combination With Docetaxel, Fluoropyrimidine Plus Oxaliplatin, Paclitaxel, or Enzalutamide in Patients With Advanced Solid Tumors [NCT01362374] | Phase 1 | 122 participants (Actual) | Interventional | 2011-07-11 | Completed |
| Phase II Study to Investigate the Treatment of Patients With NSCLC Stage IIIB and IV Without the Option of Surgery With a Combination of Cisplatin, Docetaxel and Bevacizumab [NCT01368848] | Phase 2 | 7 participants (Actual) | Interventional | 2010-04-30 | Completed |
| A Multicenter, Randomized, Open-label, Phase II Study to Evaluate the Efficacy and Safety of Neoadjuvant Treatment Consisting of Either a Docetaxel - Letrozole Combination or Letrozole Alone in Women Over 60 Years of Age Suffering From Grade I or II Opera [NCT00617968] | Phase 2 | 5 participants (Actual) | Interventional | 2003-10-31 | Completed |
| Phase I Study of the Pharmacokinetics and Pharmacodynamics of ZD6474 in Combination With Docetaxel in Advanced Solid Tumors [NCT00937417] | Phase 1 | 0 participants (Actual) | Interventional | 2008-09-30 | Withdrawn(stopped due to Withdrawn because SWOG no longer pursuing this study at this time) |
| Phase II Study of Sorafenib (Bay 43-9006) and Docetaxel in Metastatic Prostate Cancer [NCT00619996] | Phase 2 | 43 participants (Anticipated) | Interventional | 2007-03-31 | Completed |
| A Double Blind Randomised Phase 2 Trial of Docetaxel With or Without AZD6244 in wt BRAF Advanced Melanoma [NCT01256359] | Phase 2 | 80 participants (Anticipated) | Interventional | 2010-10-31 | Active, not recruiting |
| 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 2 | 6 participants (Actual) | Interventional | 2019-05-23 | Terminated(stopped due to Security and effect data from another ongoing study.) |
| [NCT01160419] | Phase 2 | 49 participants (Anticipated) | Interventional | 2009-12-31 | Active, not recruiting |
| A Prospective Randomized Phase III, Trial Comparing Consolidation Therapy With or Without Strontium-89 Following Induction Chemotherapy in Androgen-Independent Prostate Cancer [NCT00024167] | Phase 3 | 265 participants (Actual) | Interventional | 2002-04-30 | Terminated(stopped due to Terminated due to slow accrual) |
| Randomized Phase II Study of Two Different Regimens of TPF Induction Chemotherapy Regimen Followed by Radiation Therapy Plus Cetuximab (TPF-CET-HART) vs. HART and Cis-platinum, 5-FU (PF-HART) in Patients With Locally Advanced Unresectable Squamous Cell Ca [NCT01181401] | Phase 2 | 94 participants (Actual) | Interventional | 2010-08-31 | Completed |
| 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 1 | 169 participants (Actual) | Interventional | 2010-09-14 | Completed |
| A Phase II Randomized, Non-inferiority Study Comparing the Efficacy and Safety of Dalpiciclib Combined With AI With Neoadjuvant Chemotherapy in ER+ HER2- Postmenopausal Breast Cancer Patients [NCT06107673] | Phase 2 | 144 participants (Anticipated) | Interventional | 2023-09-30 | 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 3 | 272 participants (Anticipated) | Interventional | 2023-05-01 | Recruiting |
| Randomized, Open-label, Phase 3 Study of SAR408701 Versus Docetaxel in Previously Treated, Metastatic Nonsquamous, Non-small-cell Lung Cancer Patients With CEACAM5-positive Tumors [NCT04154956] | Phase 3 | 450 participants (Anticipated) | Interventional | 2020-02-06 | Recruiting |
| A Phase 1 First-in-Human Study With ABBV-155 Alone and in Combination With Taxane Therapy in Adults With Relapsed and/or Refractory Solid Tumors [NCT03595059] | Phase 1 | 169 participants (Actual) | Interventional | 2018-07-13 | Active, not recruiting |
| Open-Label, Multicenter, Phase Ⅱ Study of Docetaxel and Cisplatin Combined With Nimotuzumab As First-Line Treatment in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma [NCT03708822] | Phase 2 | 48 participants (Anticipated) | Interventional | 2018-11-01 | Recruiting |
| A Phase 3, Randomized, Open-label, Multicenter Study of the Efficacy and Safety of Pyrotinib Versus Docetaxel in Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) Harboring a HER2 Exon 20 Mutation Who Progressed on or After Treatment [NCT04447118] | Phase 3 | 151 participants (Actual) | Interventional | 2020-09-11 | Active, not recruiting |
| Phase II Trial of Cisplatin Plus Weekly Docetaxel as the First-line Treatment for Recurrent or Metastatic Nasopharyngeal Cancer [NCT01312311] | Phase 2 | 51 participants (Anticipated) | Interventional | 2006-07-31 | Recruiting |
| Concurrent Chemoradiation Versus Induction Docetaxel, Cisplatin and 5-fluorouracil (TPF) Followed by Concomitant Chemoradiotherapy in Locally Advanced Hypopharyngeal and Base of Tongue Cancer: A Randomized Phase II Study [NCT01312350] | Phase 2 | 40 participants (Actual) | Interventional | 2010-11-30 | Completed |
| Prospective Randomized Trial Comparing Induction Chemotherapy Plus Concurrent Chemoradiotherapy With Concurrent Chemoradiotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma [NCT01245959] | Phase 3 | 476 participants (Anticipated) | Interventional | 2011-01-31 | Active, not recruiting |
| A Multicenter Randomized Phase II Study to Evaluate the Benefit of Chemotherapy Plus Best Supportive Care (BSC) Versus BSC in Patients With Metastatic Oesophageal Cancer of Squamous Cell-type Who Have Not Experienced a Disease Progression or Unacceptable [NCT01248299] | Phase 2 | 105 participants (Actual) | Interventional | 2011-01-31 | Terminated |
| A Prospective, Single-center, One-arm Clinical Study of Apatinib Combined With Chemotherapy for Patients Who Progressed After First Line EGFR-TKI Treatment Without T790M Mutation [NCT03758677] | Phase 2 | 30 participants (Anticipated) | Interventional | 2020-08-01 | Not yet recruiting |
| A Phase III, Randomized, Two-armed, Triple Blinded, Parallel, Active Controlled Non-Inferiority Clinical Trial of AryoTrust (AryoGen Trastuzumab) Efficacy and Safety in Comparison to Herceptin (Genentech) in HER2-Positive Breast Cancer [NCT03425656] | Phase 3 | 108 participants (Actual) | Interventional | 2016-07-09 | Completed |
| A Randomized, Multicenter, Phase ii Study of the Efficacy and Safety of Trastuzumab-MCC-DM1 vs. Trastuzumab (Herceptin®) and Docetaxel (Taxotere®) in Patients With Metastatic HER2-positive Breast Cancer Who Have Not Received Prior Chemotherapy for Metasta [NCT00679341] | Phase 2 | 137 participants (Actual) | Interventional | 2008-09-30 | Completed |
| A Phase I, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Aflibercept in Combination With Intravenous Docetaxel Administrated Every 3 Weeks in Chinese Patients With Advanced Solid Malignancies [NCT01148615] | Phase 1 | 20 participants (Actual) | Interventional | 2010-07-31 | Completed |
| A Phase I Study Evaluating the Efficacy and Safety of Sodium Selenite in Combination With Docetaxel in Castration-resistant Prostate Cancer [NCT01155791] | Phase 1 | 2 participants (Actual) | Interventional | 2010-04-30 | Terminated |
| A Multicenter, Phase II Open Label Study of Pyrotinib Maleate Combined With Docetaxel in the First-line Treatment of HER2-positive Metastatic Breast Cancer [NCT03876587] | Phase 2 | 79 participants (Anticipated) | Interventional | 2019-03-31 | Not yet recruiting |
| A Multicenter, Double-Blind, Randomized, Parallel-Group, Phase III Study of the Efficacy and Safety of Hercules Plus Taxane Versus Herceptin® Plus Taxane as First Line Therapy in Patients With HER2-Positive Metastatic Breast Cancer [NCT02472964] | Phase 3 | 500 participants (Actual) | Interventional | 2012-07-31 | Completed |
| SAMSUNG MEDICAL CENTER [NCT03061643] | Phase 2 | 42 participants (Actual) | Interventional | 2017-02-08 | Active, not recruiting |
| Biomarkers of Response to Taxotere in Hormone-Refractory Prostate Cancer [NCT01160705] | | 73 participants (Actual) | Observational | 2009-11-30 | Completed |
| Randomized Phase II Trial of the Sequences of Anthracyline and Taxane in Locally Advanced Breast Cancer [NCT01270373] | Phase 2 | 112 participants (Anticipated) | Interventional | 2010-08-31 | Active, not recruiting |
| A Randomized Phase III Study of TaxoteRe Plus Cisplatin Versus AlImta Plus Cisplatin in 1st Line Non-squamous Cell Type Lung Cancer [NCT01282151] | Phase 3 | 148 participants (Actual) | Interventional | 2011-07-31 | Terminated(stopped due to Difficulty in recruitment due to approval of maintenance pemetrexed treatment) |
| Prospective Randomized Controlled Study on the Risk and Clinical Benefit of Chemotherapy and Intensive Endocrine Therapy for Luminal B1 Early-stage Breast Cancer [NCT03373708] | Phase 2/Phase 3 | 200 participants (Anticipated) | Interventional | 2017-12-20 | Not yet recruiting |
| A Multicenter,Exploratory Study of Anlotinib in Combination With Docetaxel Versus Docetaxel Alone in Participants With Advanced Non-Small Cell Lung Cancer After Failure of First-Line Chemotherapy [NCT03732001] | Phase 2 | 80 participants (Anticipated) | Interventional | 2018-11-08 | Recruiting |
| A Prospective, Open-label Study to Evaluate Injectable Albumin-bound Paclitaxel Versus Docetaxel for the Neoadjuvant Treatment of Breast Cancer [NCT05420454] | Phase 4 | 1,576 participants (Anticipated) | Interventional | 2022-07-10 | Recruiting |
| A Phase III Study to Investigate the Differential Influence of Prior Chemotherapy on the Efficacy of Erlotinib in Patients With Advanced Non-small Cell Lung Cancer (IIIB, IV) With or Without EGFR Gene Mutation [NCT01204307] | Phase 2 | 101 participants (Actual) | Interventional | 2010-01-31 | Completed |
| A Phase II Study of Neoadjuvant Treatment With Pegylated Liposomal Doxorubicin (Caelyx) and Cyclophosphamide +/- Trastuzumab Followed by Docetaxel in Patients With Locally Advanced Breast Cancer [NCT01206881] | Phase 2 | 45 participants (Anticipated) | Interventional | 2009-03-31 | Completed |
| A Randomised, Phase 3 Trial Comparing 3-weekly Docetaxel 75 mg/m2 (in a 3 Week Cycle) Versus 2-weekly Docetaxel 50 mg/m2 (in a 4 Week Cycle) in Combination With Darolutamide + ADT in Patients With mHSPC [NCT05676203] | Phase 3 | 250 participants (Anticipated) | Interventional | 2023-05-16 | Recruiting |
| Randomized Phase II Trial of Docetaxel (Taxotere) and Oblimersen (Antisense Oligonucleotide Directed to BCL-2) Versus Taxotere Alone in Patients With Hormone-Refractory Prostate Cancer [NCT00085228] | Phase 2 | 116 participants (Actual) | Interventional | 2004-04-30 | Completed |
| Clinical and Translational Phase II Study of Liposomal Doxorubicin Plus Docetaxel and Trastuzumab With Metformin as Primary Systemic Therapy for Operable and Locally Advanced Recombinant Human ErbB-2 (HER2) Positive Breast Cancer [NCT02488564] | Phase 2 | 49 participants (Actual) | Interventional | 2014-12-17 | Completed |
| 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 4 | 45 participants (Anticipated) | Interventional | 2019-03-01 | Not yet recruiting |
| A Phase II Study of Sequential Capecitabine Plus Oxaliplatin (XELOX) Followed by Docetaxel Plus Capecitabine (TX) in Patients With Unresectable Gastric [NCT01331928] | Phase 2 | 51 participants (Anticipated) | Interventional | 2011-01-31 | 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 1 | 180 participants (Anticipated) | Interventional | 2022-03-29 | Active, not recruiting |
| A Phase I/II Study on the Treatment With Taxotere in Combination With Xeloda in Patients With Metastatic Oesophageal Cancer or Cancer in the Cardia Region [NCT00821912] | Phase 1/Phase 2 | 93 participants (Actual) | Interventional | 2006-03-31 | Active, not recruiting |
| Randomized, Open Label, Multi-Center Study Comparing Cabazitaxel at 25 mg/m^2 and at 20 mg/m^2 in Combination With Prednisone Every 3 Weeks to Docetaxel in Combination With Prednisone in Patients With Metastatic Castration Resistant Prostate Cancer Not Pr [NCT01308567] | Phase 3 | 1,168 participants (Actual) | Interventional | 2011-05-05 | Completed |
| Phase Ⅱ/Ⅲ Clinical Study of Tumor Treating Fields（EFE-P100） Combined With Docetaxel in the Treatment of Stage IV Non-small Cell Lung Cancer Patients With Disease Progression After Platinum-based Chemotherapy and Anti-programmed Death 1(PD-1)/Programmed Ce [NCT05661240] | Phase 2/Phase 3 | 348 participants (Anticipated) | Interventional | 2022-12-20 | Not yet recruiting |
| Phase I/II Study of Gemcitabine and Docetaxel Combined With Immune Checkpoint Blockade (Retifanlimab) in Patients With Advanced Soft Tissue Sarcoma [NCT04577014] | Phase 1/Phase 2 | 74 participants (Anticipated) | Interventional | 2020-09-29 | Recruiting |
| 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 2 | 130 participants (Anticipated) | Interventional | 2019-05-29 | Active, not recruiting |
| A Randomized, Multicenter, Open Phase II Study of Cetuximab With Docetaxel, Cisplatin as Induction Chemotherapy in Unresectable, Locally Advanced Head and Neck Squamous Cell Carcinoma (HNSCC) [NCT00623558] | Phase 2 | 92 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Evaluation of Central Venous Catheters Used for Chemotherapy in Women With Breast Cancer - An Interdisciplinary Randomized Controlled Study of Complications, Material Wear, Staff- and Patient Perspectives, and Health Economy. [NCT04324346] | | 250 participants (Actual) | Interventional | 2016-04-01 | Completed |
| An Open, Multicenter, Randomized Controlled Clinical Study of Chidamide Combined With Exemestane (+/- Goserelin) Versus Neoadjuvant Chemotherapy in Patients of Stage II-III HR-positive/HER2-negative Breast Cancer [NCT05253066] | Phase 2/Phase 3 | 130 participants (Anticipated) | Interventional | 2022-02-25 | Not yet recruiting |
| 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 2 | 7 participants (Actual) | Interventional | 2011-07-31 | Terminated(stopped due to Due to slow accrual) |
| Phase I/II Trial of Combination Chemotherapy With Docetaxel, Cisplatin and 5-FU for Unresectable Advanced Esophageal Cancer. [NCT00915850] | Phase 1/Phase 2 | 32 participants (Anticipated) | Interventional | 2007-08-31 | Recruiting |
| A Randomised, Open-Label Phase 3 Trial Comparing Amrubicin Versus Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure of First-Line Chemotherapy [NCT01207011] | Phase 3 | 202 participants (Actual) | Interventional | 2010-10-31 | Completed |
| A Phase 3 Study to Evaluate the Efficacy and Safety of Docetaxel and Prednisone With or Without Lenalidomide in Subjects With Castrate-Resistant Prostate Cancer (CRPC) [NCT00988208] | Phase 3 | 1,059 participants (Actual) | Interventional | 2009-11-11 | Completed |
| A Phase II Randomized Multicenter Open Label Prospective Study of Neoadjuvant Chemotherapy Docetaxel With or Without MEK Inhibitor SELUMETINIB in Patients With Early and Locally Advanced Triple Negative Breast Cancer [NCT02685657] | Phase 2 | 164 participants (Anticipated) | Interventional | 2016-09-30 | Not yet recruiting |
| Phase II, Open, Not Randomized Clinical Trial, to Evaluate the Sequential Taxotere®, Followed by Myocet® and Cyclophosphamide First Line Treatment in her2 Negative Breast Cancer Patients [NCT00721747] | Phase 2 | 83 participants (Anticipated) | Interventional | 2008-01-31 | Active, not recruiting |
| Randomized Phase II Feasibility Study of Cetuximab Combined With 4 Cycles of TPF Followed by Platinum Based Chemo-radiation Strategies [NCT00646659] | Phase 2 | 47 participants (Actual) | Interventional | 2008-02-29 | Terminated(stopped due to Recruitment was suspended prematurely for safety concerns and closed after IDMC review) |
| Phase I/II Study of the Combination of Oxaliplatin / Docetaxel and ZACTIMA for the Treatment of Advanced Cancers of the Esophagus and Gastroesophageal Junction [NCT00732745] | Phase 1 | 9 participants (Actual) | Interventional | 2008-10-31 | Terminated(stopped due to Lost funding for Phase II portion of study) |
| An Investigator-sponsored, Phase 1/2 Trial of the Oral XPO1 Inhibitor Selinexor (KPT-330) Monotherapy and in Combination With Docetaxel for Previously Treated, Advanced KRAS Mutant Non-small Cell Lung Cancer (NSCLC) [NCT03095612] | Phase 1/Phase 2 | 40 participants (Actual) | Interventional | 2018-03-22 | Completed |
| 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 1 | 829 participants (Actual) | Interventional | 2016-06-23 | Completed |
| Multimodality Therapy for Recurrent High Risk Prostate Cancer: A Phase II Study [NCT00734851] | Phase 2 | 36 participants (Actual) | Interventional | 2008-12-31 | Terminated(stopped due to Dose Limiting Toxicities) |
| "An Open Label Study to Assess the Effect of Neoadjuvant Treatment With Docetaxel + Xeloda + Avastin on Pathological Response Rate in Inflammatory or Locally Advanced Breast Cancer" [NCT00576901] | Phase 2 | 23 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to The sample for statistical analysis of results could not be recruited within the specified timeframe upon retirement of the original principal investigator.) |
| A Phase II Clinical Trial Evaluating the Safety and Efficacy of Combination of Hyperthermia and Concurrent Chemoradiotherapy (CCRT) for Recurrent Head and Neck Cancer [NCT02567383] | Phase 2 | 45 participants (Anticipated) | Interventional | 2015-09-30 | Recruiting |
| Study of the Vascular Disrupting Agent NPI-2358 in Combination With Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer [NCT00630110] | Phase 1/Phase 2 | 172 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Randomized Phase II Trial of Pre-Operative Docetaxel-Cytoxan (TC) or Exemestane in Patients With Hormone Receptor-Positive Breast Cancers With Recurrence Scores Greater Than 10 (≥ 11) and Less Than 25 (≤ 24) [NCT00941330] | Phase 2 | 31 participants (Actual) | Interventional | 2009-07-31 | Completed |
| Docetaxel, Gemcitabine and Bevacizumab as Salvage Therapy for Metastatic Breast Cancer [NCT00754351] | Phase 2 | 48 participants (Actual) | Interventional | 2008-09-30 | Completed |
| Clinical Study of Apatinib Mesylate Tablets Combined With Docetaxel Monotherapy as Second-line Therapy of Advanced EGFR Wild-type, Non-squamous, Non-small-cell Lung Cancer [NCT02852798] | | 60 participants (Anticipated) | Observational | 2016-08-31 | Not yet recruiting |
| Pharmacodynamic Biomarkers of Standard Anti-microtubule Drugs as Assessed by Early Tumor Biopsy [NCT03393741] | | 35 participants (Anticipated) | Observational | 2018-01-29 | Recruiting |
| Phase IV Clinical Study Evaluating The Efficacy of Chemoradiotherapy Following Neoadjuvant Treatment With Docetaxel and Cisplatin in Indifferentiated and Non-keratinized Squamous Cell Carcinoma of Nasopharynx [NCT00772681] | Phase 4 | 57 participants (Actual) | Interventional | 2004-10-31 | Completed |
| An Open Label Study of the Effect of First Line Combination Treatment With Avastin and Docetaxel on Disease Response in Patients With Metastatic Breast Cancer [NCT00774241] | Phase 4 | 0 participants (Actual) | Interventional | 2010-01-31 | Withdrawn(stopped due to Study was put on hold then out of Medical Plan therefore cancelled) |
| 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 2 | 63 participants (Actual) | Interventional | 2004-02-29 | Terminated(stopped due to Treatment became standard.) |
| Study Comparing Paclitaxel Plus Carboplatin Versus Anthracyclines Followed by Docetaxel as Adjuvant Chemotherapy for Triple Negative Breast Cancer [NCT04031703] | Phase 3 | 647 participants (Actual) | Interventional | 2011-01-01 | Completed |
| A Phase II Study of Docetaxel - Carboplatin as Second Line Treatment in Patients With Refractory or Relapsed Small Cell Lung Cancer [NCT00686985] | Phase 2 | 55 participants (Anticipated) | Interventional | 2007-09-30 | Recruiting |
| Effect of Ketoconazole Inhibition of CYP3A on Urinary Excretion of Docetaxel [NCT00697437] | Phase 2 | 10 participants (Actual) | Interventional | 2006-10-31 | Completed |
| Nab-paclitaxel Compared With Docetaxel Combined With Epirubicin and Cyclophosphamide in the Neoadjuvant Chemotherapy Breast Cancer [NCT05251766] | Phase 1 | 30 participants (Anticipated) | Interventional | 2022-04-20 | Not yet recruiting |
| A Randomized Phase III Study of Vitamins B6 and B12 to Prevent Chemotherapy-Induced Neuropathy in Cancer Patients. [NCT00659269] | Phase 3 | 319 participants (Actual) | Interventional | 2006-07-31 | Completed |
| Phase I/II, Open Label Study of Sequential Taxotere® (Docetaxel) and Gleevec® (Imatinib Mesylate) in Hormone Refractory Prostate Cancer [NCT00861471] | Phase 1/Phase 2 | 24 participants (Actual) | Interventional | 2005-05-31 | Terminated(stopped due to due to slow accrual) |
| Open Label, Randomized Multicenter Study Docetaxel + 5-fluorouracil + Cisplatin Compared to Cisplatin + 5-fluorouracil in Patients With Metastatic or Locally Recurrent Gastric Cancer Previously Untreated With Chemotherapy for Advanced Disease [NCT00811447] | Phase 3 | 243 participants (Actual) | Interventional | 2008-11-30 | Completed |
| 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 1 | 104 participants (Actual) | Interventional | 2009-02-28 | Terminated |
| Optimization of Erlotinib for the Treatment of Patients With Advanced Non Small Cell Lung Cancer: an Italian Randomized Trial [NCT00637910] | Phase 3 | 850 participants (Anticipated) | Interventional | 2007-11-30 | Recruiting |
| L-TIL Plus Tislelizumab as Second Line Therapy for PD-1 Inhibitor Resistant Advanced NSCLC Patients [NCT05878028] | Phase 2 | 33 participants (Anticipated) | Interventional | 2022-09-16 | Recruiting |
| A Phase 1, Open-Label, Multicenter Study to Assess Safety, Tolerability, Pharmacokinetics, and Preliminary Anti-Tumor Activity of Ascending Doses of AZD4635 Both as Monotherapy and in Combination in Patients With Advanced Solid Malignancies [NCT02740985] | Phase 1 | 313 participants (Actual) | Interventional | 2016-06-17 | Completed |
| Pharmacokinetics and Pharmacogenetics-based Adaptive Dosing of 5-fu (5-Fluorouracile) in Head & Neck Cancer Patient Undergoing Docetaxel, Cisplatin, 5-Fluorouracile (=TPF) Therapy [NCT02484677] | Phase 4 | 12 participants (Actual) | Interventional | 2015-07-15 | Completed |
| Docetaxel-epirubicin Plus Bevacizumab as First Line Therapy for Patients With Metastatic and HER2 Negative Breast Cancer. A Multicenter Phase I-II Study [NCT00705315] | Phase 1/Phase 2 | 46 participants (Anticipated) | Interventional | 2008-05-31 | Completed |
| Feasibility and Efficacy of Molecular Analysis-Directed Individualized Therapy Based of Tumoral mRNA Levels of ERCC1, RRM1 and BRCA1 in Advanced Non-Small-Cell Lung Cancer [NCT00705549] | Phase 2 | 88 participants (Actual) | Interventional | 2008-02-29 | Terminated(stopped due to Due to poor accrual) |
| A Randomized Phase II Study of Erlotinib Compared to Single Agent Chemotherapy-erlotinib Combination in Pretreated Patients With Advanced NSCLC (NVALT10 Study) [NCT00835471] | Phase 2 | 195 participants (Actual) | Interventional | 2009-03-31 | Completed |
| An Open Label, Dose Escalation, Safety and Pharmacokinetic Phase 1 Study With AVE8062 Administered as a 30 Minutes Intravenous Infusion Followed by Docetaxel Administered as an 1 Hour Intravenous Infusion 24 Hours-Apart Every 3 Weeks in Patients With Adva [NCT01907685] | Phase 1 | 58 participants (Actual) | Interventional | 2006-06-30 | Completed |
| Phase II Study: Neoadjuvant Gemcitabine, Docetaxel and Capecitabine Followed by Neoadjuvant Radiation Therapy With Gemcitabine and Capecitabine in the Treatment of Stage II and III Pancreatic Adenocarcinoma [NCT01065870] | Phase 2/Phase 3 | 64 participants (Anticipated) | Interventional | 2009-12-31 | Recruiting |
| A Randomized, Open Label Phase 2/3 Study Comparing Cobolimab + Dostarlimab + Docetaxel To Dostarlimab + Docetaxel To Docetaxel Alone In Participants With Advanced Nonsmall Cell Lung Cancer Who Have Progressed On Prior Anti-PD-(L)1 Therapy And Chemotherapy [NCT04655976] | Phase 2/Phase 3 | 758 participants (Actual) | Interventional | 2020-12-08 | Active, not recruiting |
| An Open-label, Multicenter, Phase 1a/1b Study of IGM-8444 as a Single Agent and in Combination in Subjects With Relapsed, Refractory, or Newly Diagnosed Cancers [NCT04553692] | Phase 1 | 430 participants (Anticipated) | Interventional | 2020-09-23 | Recruiting |
| Apatinib Plus Docetaxel as 2nd Line Treatment in Patients With Advanced Non-squamous and Non-small Cell Lung Cancer [NCT02780778] | Phase 2/Phase 3 | 20 participants (Anticipated) | Interventional | 2016-05-31 | Recruiting |
| A Randomized Phase II Study of Reolysin in Patients With Previously Treated Advanced or Metastatic, Non Small Cell Lung Cancer Receiving Standard Salvage Therapy. [NCT01708993] | Phase 2 | 166 participants (Actual) | Interventional | 2012-12-10 | Completed |
| A Randomized Phase II Study of Reolysin in Combination With Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Patients With Metastatic Castration Resistant Prostate Cancer [NCT01619813] | Phase 2 | 85 participants (Actual) | Interventional | 2012-12-14 | Completed |
| A Phase III Study of Neoadjuvant Docetaxel and Androgen Suppression Plus Radiation Therapy Versus Androgen Suppression Alone Plus Radiation Therapy for High-Risk Localized Adenocarcinoma of the Prostate [NCT00651326] | Phase 3 | 48 participants (Actual) | Interventional | 2008-06-02 | Terminated(stopped due to Poor accrual) |
| A Phase I Study of a Second Generation Clusterin Antisense Oligonucleotide (OGX-011) in Combination With Docetaxel [NCT00471432] | Phase 1 | 40 participants (Actual) | Interventional | 2003-04-04 | Completed |
| A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours [NCT00372736] | Phase 1 | 27 participants (Actual) | Interventional | 2006-07-27 | Completed |
| A Phase I Study of AEG35156 in Combination With Docetaxel in Patients With Solid Tumors [NCT00357747] | Phase 1 | 10 participants (Actual) | Interventional | 2005-06-09 | Completed |
| A Randomized Phase II Study of OGX-011 in Combination With Docetaxel and Prednisone or Docetaxel and Prednisone Alone in Patients With Metastatic Hormone Refractory Prostate Cancer [NCT00258388] | Phase 2 | 82 participants (Actual) | Interventional | 2005-09-28 | Completed |
| A Phase II Study of a Second Generation Clusterin Antisense Oligonucleotide (OGX-011) in Combination With Docetaxel in Advanced Breast Cancer [NCT00258375] | Phase 2 | 15 participants (Actual) | Interventional | 2005-10-21 | Completed |
| A Phase I and Pharmacokinetics Study of Docetaxel in Combination With Capecitabine and Cisplatin in Solid Tumors [NCT00084734] | Phase 1 | 61 participants (Actual) | Interventional | 2002-05-31 | Completed |
| A Phase I/II Study Of Increasing Doses Of Epirubicin And Docetaxel Plus Pegfilgrastim For Locally Advanced Or Inflammatory Breast Cancer [NCT00066443] | Phase 1/Phase 2 | 93 participants (Actual) | Interventional | 2003-11-03 | Completed |
| Exploratory Study of Molecular Phenotype Changes and Personalized Treatment for Patients With Castration Resistant Prostate Cancer [NCT02208583] | | 150 participants (Anticipated) | Interventional | 2014-06-30 | Recruiting |
| A Pilot Dose Escalation Phase I Trial of a Densified Chemotherapy Association of Docetaxel and Epirubicin Driven by Mathematical Modeling in Metastatic Breast Cancer Patients: The MODEL1 Study [NCT02392845] | Phase 1 | 17 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Phase 1/2 Study of PX-866 and Docetaxel in Patients With Solid Tumors [NCT01204099] | Phase 1/Phase 2 | 223 participants (Actual) | Interventional | 2010-09-30 | Completed |
| A Randomized Phase 3 Study Comparing Standard First-Line Docetaxel/Prednisone to Docetaxel/Prednisone in Combination With Custirsen (OGX-011) in Men With Metastatic Castrate Resistant Prostate Cancer [NCT01188187] | Phase 3 | 1,022 participants (Actual) | Interventional | 2010-11-30 | Completed |
| The Study of Intraperitoneal Docetaxel Plus S-1 for Malignant Ascites Due to Far Advanced Gastric Cancer [NCT02779608] | Phase 2 | 50 participants (Anticipated) | Interventional | 2017-01-20 | Recruiting |
| A Phase 1/2, Modified Dose Escalation, Open Label Trial to Determine the Therapeutic Effect and Safety of INCB007839 Combined With Trastuzumab in Patients With Previously Untreated HER2 Positive Metastatic Breast Cancer [NCT00864175] | Phase 1/Phase 2 | 68 participants (Actual) | Interventional | 2007-07-31 | Terminated(stopped due to Incyte suspended development of the compound.) |
| Plinabulin vs. Pegfilgrastim in Reducing the Duration of Severe Neutropenia in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) [NCT04227990] | Phase 2 | 115 participants (Actual) | Interventional | 2017-11-27 | Completed |
| A Phase I Dose Escalation Trial of BIBW 2992 Administration for 20, 13 or 6 Days in Combination With Docetaxel Every 21 Days [NCT02171741] | Phase 1 | 31 participants (Actual) | Interventional | 2005-04-30 | Completed |
| A Phase II Randomized Trial of Induction Chemotherapy Versus no Induction Chemotherapy Followed by Definitive Chemoradiotherapy in Patients With Inoperable Thoracic Esophageal Cancer [NCT02403531] | Phase 2 | 110 participants (Actual) | Interventional | 2015-05-01 | Completed |
| A Phase I/II Multicenter, Open-Label Study of YM155 Plus Docetaxel in Subjects With Advanced Hormone Refractory Prostate Cancer and Other Solid Tumors [NCT00514267] | Phase 1/Phase 2 | 32 participants (Actual) | Interventional | 2007-05-31 | Completed |
| A Randomized, Open-label Phase III Trial to Evaluate the Efficacy and Safety of Pertuzumab Retreatment in Previously Pertuzumab, Trastuzuamb and Chemotherapy Treated Her2-Positive Metastatic Advanced Breast Cancer [NCT02514681] | Phase 3 | 370 participants (Anticipated) | Interventional | 2015-08-01 | Active, not recruiting |
| A Study on Neoadjuvant Therapy for Her-2 Positive Breast Cancer and the Prognosis Detecting Circulating Tumor Cells [NCT02510781] | Phase 2 | 200 participants (Anticipated) | Interventional | 2015-01-31 | Recruiting |
| Phase II Study of Trastuzumab in Combination With Chemotherapy (Docetaxel Plus Capecitabine) For First Line Treatment of Her2-Positive Advanced Gastric or Gastro-Esophageal Junction Cancer [NCT02004769] | Phase 2 | 67 participants (Actual) | Interventional | 2013-11-30 | Completed |
| A Prospective Open-label, Randomized, Two-arm Pilot Study to Investigate the Toxicity and Pharmacokinetics of 2-Weekly and 3-Weekly Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer. [NCT03343977] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2018-02-14 | Withdrawn(stopped due to Study withdrawn for technical reasons) |
| A Multicenter, Placebo-Controlled, Phase III Trial of Standard Adjuvant Chemotherapy Plus Moxifloxacin in Operable Breast Cancer [NCT05114720] | Phase 3 | 520 participants (Anticipated) | Interventional | 2021-11-11 | Recruiting |
| Evaluation of Pathological Response in Patient With Resectable Gastric Cancer and Perioperative Chemotherapy FLOT Versus XELOX; Phase 2 [NCT04937738] | Phase 2 | 284 participants (Anticipated) | Interventional | 2021-07-21 | Active, not recruiting |
| A Phase II, Open-label, Multicenter, Randomized Study to Assess the Efficacy and Safety of GSK1120212 Compared With Docetaxel in 2nd Line Subjects With Targeted Mutations (KRAS, NRAS, BRAF, MEK1) in Locally Advanced or Metastatic Non-small Cell Lung Cance [NCT01362296] | Phase 2 | 134 participants (Actual) | Interventional | 2011-09-30 | Completed |
| An Open-label, Randomized, Phase II Study of Erlotinib Monotherapy Versus Docetaxel and Cisplatin as Neoadjuvant Therapy in Patients of Stage IIIA Lung Adenocarcinoma With Epidermal Growth Factor Receptor Gene Mutation. [NCT02036359] | Phase 2 | 76 participants (Anticipated) | Interventional | 2012-05-31 | Recruiting |
| A Phase IV, Multicenter, Open-Label, Single-Arm Study of Pertuzumab (in Combination With Trastuzumab and Docetaxel) in First Line Treatment of Indian Patients With HER2-Positive Advanced (Metastatic or Locally Recurrent) Breast Cancer [NCT02445586] | Phase 4 | 52 participants (Actual) | Interventional | 2015-08-17 | Completed |
| Chemotherapy in Combination With Erlotinib, or Sequential Chemotherapy for Erlotinib for Treatment, EGFR - TKI Resistance of EGFR Mutations in Patients With NSCLC Randomized Controlled Phase II Clinical Study [NCT02037997] | Phase 2 | 80 participants (Anticipated) | Interventional | 2013-12-31 | Recruiting |
| Open Label, Non Controlled, Non Randomized, Interventional Study to Evaluate the Response Rate After Induction Therapy With DocEtaxel and CIsplatin in Unresectable Locally Advanced Squamous Cell Carcinoma of heaD and nEck [NCT02061631] | Phase 2 | 35 participants (Actual) | Interventional | 2014-05-31 | Completed |
| A Phase 2, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sitravatinib in Combination With Tislelizumab in Patients With Locally Advanced Unresectable or Metastatic Esophageal Squamous Cell Carcinoma That Progressed on or After Ant [NCT05461794] | Phase 2 | 100 participants (Anticipated) | Interventional | 2022-10-03 | Active, not recruiting |
| "Preventive HIPEC in Combination With Perioperative FLOT Versus FLOT Alone for Resectable Diffuse Type Gastric and Gastroesophageal Junction Type II/III Adenocarcinoma - The Phase III PREVENT Trial of the AIO /CAOGI /ACO" [NCT04447352] | Phase 3 | 200 participants (Anticipated) | Interventional | 2020-12-17 | Recruiting |
| A Prospective, Multisite, Randomized, Open-label Phase III Clinical Trial (CLOVER Study)Comparing 4 Cycles With 6 Cycles of TC (Docetaxel+Cyclophosphamide) Adjuvant Chemotherapy for 1-3 Lymph Node Positive ER+/HER2- Early Breast Cancer [NCT03926091] | Phase 3 | 2,172 participants (Anticipated) | Interventional | 2019-04-01 | Recruiting |
| A Phase 1b Study of Combination of Avelumab and Taxane Based Chemotherapy in Platinum Refractory or Ineligible Metastatic Urothelial Cancer [NCT03575013] | Phase 1 | 21 participants (Anticipated) | Interventional | 2018-10-29 | Active, 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 2 | 470 participants (Anticipated) | Interventional | 2018-01-02 | Recruiting |
| 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 1 | 150 participants (Anticipated) | Interventional | 2016-11-30 | Recruiting |
| Effect of Chemotherapy Alone vs. Chemotherapy Followed by Surgical Resection on Survival and Quality of Life in Patients With Limited-metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction - A Phase III Trial of Arbeitsgemeinschaft Internist [NCT02578368] | Phase 3 | 271 participants (Anticipated) | Interventional | 2016-02-29 | Recruiting |
| [NCT02095717] | Phase 2 | 50 participants (Actual) | Interventional | 2014-03-31 | Terminated(stopped due to The trial was stopped for futility in view of the results of the interim analysis) |
| Randomized Controlled Trial of S-1 Maintenance Therapy in Metastatic Esophagogastric Cancer [NCT02128243] | Phase 2 | 242 participants (Actual) | Interventional | 2014-09-30 | Completed |
| A Phase II Study of Palbociclib for Previously Treated Cell Cycle Gene Alteration Positive Patients With Stage IV Squamous Cell Lung Cancer (Lung-Map Sub-Study) [NCT02785939] | Phase 2/Phase 3 | 53 participants (Actual) | Interventional | 2014-09-30 | Completed |
| A Phase I Dose Escalation Clinical Trial of Apatinib Tablets Plus Docetaxel as Second-line Treatment in Locally Advanced or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma [NCT03071042] | Phase 1 | 12 participants (Anticipated) | Interventional | 2015-10-31 | Recruiting |
| 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 2 | 0 participants (Actual) | Interventional | 2018-09-30 | Withdrawn(stopped due to Trial not initiated) |
| A Single-arm, Multicenter, Phase II Clinical Study of Docetaxel for Injection (Albumin-bound) in Combination With Bevacizumab in Patients With Platinum-Resistant Recurrent Ovarian Cancer [NCT05325229] | Phase 2 | 94 participants (Anticipated) | Interventional | 2022-08-18 | Recruiting |
| Randomized Phase II Study of Suramin and Docetaxel Versus Docetaxel in Non-Small Cell Lung Cancer After Failure of First-Line Chemotherapy [NCT01671332] | Phase 2 | 80 participants (Actual) | Interventional | 2012-06-30 | Completed |
| Erlotinib Treatment Beyond Progression in EGFR Mutant or Patients Who Have Responded EGFR TKI in Stage IIIB/IV NSCLC [NCT02064491] | Phase 2 | 18 participants (Actual) | Interventional | 2014-02-28 | Completed |
| PRIMAL STUDY: A Phase 1b, Open-label, Multicenter, Multinational Study of PEGylated Recombinant Human Hyaluronidase (PEGPH20) Combined With Docetaxel (PDoc) in Subjects With Recurrent Previously Treated Locally Advanced or Metastatic Non-small Cell Lung C [NCT02346370] | Phase 1 | 16 participants (Actual) | Interventional | 2015-02-10 | Terminated(stopped due to Changing standard of care therapy regimen) |
| An Open-label, Randomized, Phase III, Multicenter Clinical Trial Comparing the Efficacy and Safety of Individualized Intraperitoneal and System Chemotherapy Versus System Chemotherapy as First-line Chemotherapy for Advanced Gastric Cancer [NCT03061058] | Phase 3 | 240 participants (Anticipated) | Interventional | 2013-04-01 | Recruiting |
| Phase 3 Study of Weekly Paclitaxel in Combination With Cisplatin as Adjuvant Chemotherapy for Early Stage Human Epidermal Growth Factor Receptor-2 (HER2) Negative Breast Cancer in High-risk Women [NCT03201861] | Phase 3 | 762 participants (Anticipated) | Interventional | 2017-07-27 | Recruiting |
| A Phase I Open-Label, Safety, Pharmacokinetic and Preliminary Efficacy Study of CriPec® Docetaxel in Patients With Solid Tumours [NCT02442531] | Phase 1 | 33 participants (Actual) | Interventional | 2015-08-31 | Completed |
| Nedaplatin (Jiebaishu®) and Docetaxel in Comparison With Cisplatin and Docetaxel Regimen for the First Line Treatment of Advanced Squamous Cell Carcinoma of Lung(IIIB/IV): Randomized, Controlled, Multicentre Study [NCT02088515] | Phase 4 | 290 participants (Actual) | Interventional | 2013-12-31 | Completed |
| Docetaxel, Estramustine and Short Term Androgen Withdrawal for Patients With a Rising PSA After Definitive Local Treatment [NCT00165399] | Phase 2 | 62 participants (Actual) | Interventional | 2004-03-31 | Completed |
| Shorter Anthracycline-Free Chemo Immunotherapy Adapted to Pathological Response in Early Triple Negative Breast Cancer (SCARLET), A Randomized Phase III Study [NCT05929768] | Phase 3 | 2,400 participants (Anticipated) | Interventional | 2023-09-15 | Recruiting |
| A Phase I Study of AZD8186 in Combination With Docetaxel in Patients With PTEN Mutated or PIK3CB Mutated Advanced Solid Tumors, Potentially Amenable to Docetaxel [NCT03218826] | Phase 1 | 23 participants (Actual) | Interventional | 2018-09-24 | Active, not 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 2 | 90 participants (Anticipated) | Interventional | 2021-08-31 | Not yet recruiting |
| Randomized, Open-label, Parallel-group, Multi-centre Phase II Clinical Trial of Active Cellular Immunotherapy With Preparation DCVAC/PCa in Patients With Castrate-resistant Prostate Cancer [NCT02105675] | Phase 2 | 60 participants (Anticipated) | Interventional | 2012-02-29 | Completed |
| Clinical Phase Ib/II Trial of L-NMMA Plus Taxane Chemotherapy in the Treatment of Refractory Locally Advanced or Metastatic Triple Negative Breast Cancer Patients [NCT02834403] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2016-11-30 | Completed |
| 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 3 | 456 participants (Anticipated) | Interventional | 2022-05-11 | Recruiting |
| Docetaxel and Prostvac for Metastatic Castration Sensitive Prostate Cancer [NCT02649855] | Phase 2 | 74 participants (Actual) | Interventional | 2016-01-19 | Active, not recruiting |
| An Open-label Randomized Multinational Phase 3 Trial of Nivolumab Versus Docetaxel in Previously Treated Subjects With Advanced or Metastatic Non-small Cell Lung Cancer (CheckMate 078: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 078) [NCT02613507] | Phase 3 | 639 participants (Actual) | Interventional | 2015-12-11 | Completed |
| Phase II Randomized Study of Docetaxel With or Without Thalidomide in Patients With Androgen-Independent Metastatic Prostate Cancer [NCT00020046] | Phase 2 | 0 participants | Interventional | 1999-12-31 | Completed |
| Phase II Clinical Study of Darsilide Combined With Exemestane+Goserelin Neoadjuvant Endocrine Therapy in HR Positive and HER2 Negative Premenopausal Breast Cancer Patients [NCT06009627] | Phase 2/Phase 3 | 119 participants (Anticipated) | Interventional | 2023-04-11 | Recruiting |
| Immuno-Chemotherapy as Single Treatment Modality for Larynx Preservation (ICoLP) [NCT04030455] | Phase 2 | 25 participants (Anticipated) | Interventional | 2019-08-07 | Recruiting |
| First Line Treatment of Elderly Patients With Advanced or Metastatic NSCLC With Docetaxel and Bevacizumab [NCT02179567] | Phase 2 | 26 participants (Actual) | Interventional | 2010-03-31 | Terminated(stopped due to Terminated due to poor accrual) |
| An Open-label Study of Xeloda Plus Taxotere on Treatment Response in Patients With HER2-neu-negative, and the Addition of Herceptin for HER2-neu-positive Breast Cancer [NCT00127933] | Phase 4 | 157 participants (Actual) | Interventional | 2005-08-31 | Completed |
| CAMPFIRE: Children's and Young Adult Master Protocol for Innovative Pediatric Research [NCT05999994] | Phase 2 | 105 participants (Anticipated) | Interventional | 2020-01-22 | Recruiting |
| A Randomized Phase II Trial of Docetaxel or Cabazitaxel With or Without Darolutamide in Men With Metastatic Castration-resistant Prostate Cancer [NCT05762536] | Phase 2 | 245 participants (Anticipated) | Interventional | 2023-10-19 | Recruiting |
| DART 2.0: ctHPV-DNA Informed De-Escalated Adjuvant and Definitive Radiation Therapy [NCT05541016] | Phase 2 | 320 participants (Anticipated) | Interventional | 2023-02-21 | Recruiting |
| A Phase 3, Randomized, Double-blind Study of Pembrolizumab (MK-3475) Plus Docetaxel Plus Prednisone Versus Placebo Plus Docetaxel Plus Prednisone in Participants With Chemotherapy-naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Prog [NCT04907227] | Phase 3 | 81 participants (Actual) | Interventional | 2020-09-23 | Terminated(stopped due to The data did not support study endpoints) |
| 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 2 | 123 participants (Actual) | Interventional | 2010-02-05 | Completed |
| GORG - 002 Randomized Phase III Trial to Determine the Effectiveness of High Dose Versus Standard Dose of Vitamin D2 (Ergocalciferol) Given With Docetaxel in Patients With Metastatic Breast Cancer [NCT00944424] | Phase 3 | 260 participants (Anticipated) | Interventional | 2009-07-31 | Recruiting |
| Phase II Multicenter Study in the Preoperative Treatment of Gastric Adenocarcinoma Consisting of Chemotherapy Using Docetaxel-cisplatin-5FU + Lenograstim Followed by Chemoradiation Based 5FU and Oxaliplatin [NCT01565109] | Phase 2 | 34 participants (Anticipated) | Interventional | 2009-03-31 | Recruiting |
| "A Phase II Trial of Celecoxib Plus Chemotherapy [Docetaxel or Pemetrexed] in Patients With Previously Treated, COX Dependent Recurrent Non-Small Cell Lung Cancer" [NCT00520845] | Phase 2 | 23 participants (Actual) | Interventional | 2007-10-31 | Terminated(stopped due to slow accrual) |
| Perioperative FLOT Versus Adjuvant XELOX for Locally Advanced Gastric Cancer - a Randomized Controlled Study [NCT05264896] | Phase 3 | 110 participants (Anticipated) | Interventional | 2022-03-21 | Recruiting |
| CSP #553 - Adjuvant Therapy in Prostate Carcinoma Treatment [NCT00132301] | Phase 3 | 298 participants (Actual) | Interventional | 2006-06-30 | Completed |
| A Prospective Randomized Phase Ⅱ Study of Nimotuzumab Combined With Chemoradiotherapy for Unresectable, Locally Advanced Squamous Cell Lung Cancer [NCT02577341] | Phase 2 | 122 participants (Actual) | Interventional | 2015-08-31 | Completed |
| A Multicenter, Randomized, Double Blind Study Comparing the Efficacy and Safety of Aflibercept Versus Placebo Administered Every 3 Weeks in Patients Treated With Docetaxel/ Prednisone for Metastatic Androgen-independent Prostate Cancer [NCT00519285] | Phase 3 | 1,224 participants (Actual) | Interventional | 2007-08-31 | Completed |
| Effect of Neoadjuvant Chemotherapy Followed by Concurrent Chemo-radiotherapy on Nutritional Status in Locoregionally Advanced Nasopharyngeal Carcinoma Patients: Prospective Observational Study [NCT02575547] | | 186 participants (Actual) | Observational | 2015-06-30 | Completed |
| Multicenter Phase II Trial of Nintedanib (Vargatef®) Plus Docetaxel in Second Line of Treatment in Patients With no Squamous Non Small Cell Lung Cancer Refractory to First Line Chemotherapy [NCT02531737] | Phase 2 | 59 participants (Actual) | Interventional | 2015-09-30 | Completed |
| Phase II Study to Evaluate Induction Chemotherapy Using Docetaxel, Cisplatin and Fluorouracil Followed by Weekly Docetaxel and Cetuximab in Concurrence With Intensity-modulated Radiotherapy for Locally Recurrent Nasopharyngeal Carcinoma (NPC) [NCT01326559] | Phase 2 | 33 participants (Actual) | Interventional | 2010-06-30 | Completed |
| A Phase II Trial of Postoperative Chemotherapy and Chemo-radiotherapy for Resected Adenocarcinoma of the Stomach and Gastro-esophageal Junction [NCT00718913] | Phase 2 | 40 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Phase II, Multicenter, Randomized, Open Label Study of a Sequential Treatment of Intermittent Erlotinib and Docetaxel Versus Erlotinib in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer After Failure of a Prior Chemotherapy Regimen [NCT00908336] | Phase 2 | 70 participants (Anticipated) | Interventional | 2009-03-31 | Recruiting |
| Docetaxel and Cetuximab in Patients With Docetaxel-resistant Hormone-refractory Prostate Cancer (HRPC). A Multicenter Phase II Trial [NCT00728663] | Phase 2 | 35 participants (Actual) | Interventional | 2008-06-30 | Completed |
| Phase II, Multicentre, Uncontrolled Pilot Study to Evaluate Safety and Efficacy of the Combination of Cetuximab and Chemotherapy (Docetaxel, Cisplatin, 5-fluorouracil) as Neoadjuvant Therapy Followed Concomitant Chemoradiotherapy (Cisplatin) Plus Cetuxima [NCT00733889] | Phase 2 | 50 participants (Actual) | Interventional | 2006-12-31 | Completed |
| A Randomized, Open Label, Multicenter, Phase III, 2-Arm Study of Androgen Deprivation With Leuprolide, +/- Docetaxel for Clinically Asymptomatic Prostate Cancer Subjects With a Rising PSA Following Definitive Local Therapy [NCT00514917] | Phase 3 | 413 participants (Actual) | Interventional | 2007-07-31 | Terminated(stopped due to Company decision to discontinue the study, not due to any safety or efficacy concerns) |
| PREDIX HER2 - Neoadjuvant Response-guided Treatment of HER2 Positive Breast Cancer. Part of a Platform of Translational Phase II Trials Based on Molecular Subtypes [NCT02568839] | Phase 2/Phase 3 | 202 participants (Actual) | Interventional | 2014-11-30 | Active, not recruiting |
| A Multicenter, Open-label, Phase Ib/II Study of Docetaxel for Injection (Albumin-bound) and SG001 in Combination With Cisplatin and Simultaneous Radiotherapy Versus Paclitaxel in Combination With Cisplatin and Simultaneous Radiotherapy for Locally Advance [NCT06136988] | Phase 1/Phase 2 | 129 participants (Anticipated) | Interventional | 2023-12-31 | Not yet recruiting |
| Phase II Clinical Study of Cadonilimab Combination With Chemotherapy With or Without the Anti-CD47 Antibody AK117 Neoadjuvant/Adjuvant Therapy for Resectable Gastric or Gastroesophageal Junction Adenocarcinoma [NCT05960955] | Phase 2 | 90 participants (Anticipated) | Interventional | 2023-11-13 | Recruiting |
| A Phase I Study of Intraperitoneal Docetaxel in Combination With 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) for Gastric Cancer Patients With Peritoneal Carcinomatosis [NCT04583488] | Phase 1 | 30 participants (Anticipated) | Interventional | 2020-11-01 | Recruiting |
| A Phase 1b/2 Study of Ibrutinib Combination Therapy in Selected Advanced Gastrointestinal and Genitourinary Tumors [NCT02599324] | Phase 1/Phase 2 | 263 participants (Actual) | Interventional | 2015-12-01 | Completed |
| Phase II Study of Docetaxel + Cetuximab + Concurrent Re-Irradiation (Intensity -Modulated Radiation Therapy, IMRT) for Patients With Locoregionally Recurrent Head and Neck Cancer [NCT00713219] | Phase 2 | 14 participants (Actual) | Interventional | 2008-07-31 | Completed |
| International Randomized Study to Evaluate the Addition of Docetaxel to the Combination of Cisplatin-5-fluorouracil (TCF) vs. Cisplatin-5-fluorouracil (CF) in the Induction Treatment of Nasopharyngeal Carcinoma (NPC) in Children and Adolescents [NCT00565448] | Phase 2 | 75 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Phase I/II Study of Dasatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer [NCT00439270] | Phase 1/Phase 2 | 49 participants (Actual) | Interventional | 2007-07-31 | Completed |
| Randomized, Single-blind, Multicenter, Parallel Group Clinical Trial to Assess Pharmacokinetic Parameters, Safety of NNG-TMAB (Trastuzumab) in Combination With Docetaxel on Recurrent or Metastatic Breast Cancer Patients With Positive HER2. [NCT05301530] | Phase 1 | 50 participants (Actual) | Interventional | 2019-05-27 | Completed |
| Phase II Study of Imatinib Mesylate and Docetaxel in Pretreated Patients With Metastatic NSCLC [NCT01083589] | Phase 2 | 22 participants (Actual) | Interventional | 2005-01-31 | Completed |
| Open Label, Phase II Study of Capecitabine (Xeloda®) as Fluoropyrimidine of Choice in Combination With Chemotherapy in Patients With Advanced and/or Metastatic Gastric Cancer Suitable for Treatment With a Fluoropyrimidine-Based Regimen [NCT00454636] | Phase 2 | 158 participants (Actual) | Interventional | 2007-03-31 | Completed |
| A Single Arm, Open-label Study to Evaluate the Efficacy on Tumor Response and the Safety of Bevacizumab and Trastuzumab Combination and Sequential Capecitabine in Patients With HER2 +Ive Locally Recurrent or Metastatic Breast Cancer After Early Relapse to [NCT00964704] | Phase 2 | 0 participants (Actual) | Interventional | 2011-03-31 | Withdrawn(stopped due to No patients have been recruited therefore study has been cancelled) |
| A Randomized, Open Label Study to Compare the Complete Pathological Response Rate Achieved With 4 Combinations of Herceptin, Docetaxel and Pertuzumab in Patients With Locally Advanced, Inflammatory or Early Stage HER2 Positive Breast Cancer [NCT00545688] | Phase 2 | 417 participants (Actual) | Interventional | 2006-06-26 | Completed |
| "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 2 | 189 participants (Actual) | Interventional | 2007-04-24 | Completed |
| A Phase I/II Study of S-1 and Weekly Docetaxel for Metastatic Gastric Carcinoma [NCT00980382] | Phase 1/Phase 2 | 85 participants (Actual) | Interventional | 2004-09-30 | Completed |
| A Phase II Randomized Study of the Combination of Ribociclib Plus Goserelin Acetate With Hormonal Therapy Versus Physician Choice Chemotherapy in Premenopausal or Perimenopausal Patients With Hormone Receptor-positive/ HER2-negative Inoperable Locally Adv [NCT03839823] | Phase 2 | 223 participants (Actual) | Interventional | 2019-02-25 | Completed |
| A Phase II, Double-blind, Placebo Controlled, Randomized Study to Assess the Efficacy and Safety of ZD6474 in Combination With Docetaxel (Taxotere™) vs Docetaxel Alone as 2nd Line Treatment for Advanced Breast Cancer (ABC). [NCT00494481] | Phase 2 | 64 participants (Actual) | Interventional | 2006-01-31 | Completed |
| S-1 Plus Docetaxel(DS) Versus S-1 Plus Oxaliplatin(SOX) as Postoperative Therapy for Stage II / III Gastric Cancer, a Randomized Controlled Trial [NCT03961867] | Phase 3 | 440 participants (Anticipated) | Interventional | 2020-09-15 | Recruiting |
| A Randomized, Open-label Study of the Effect of Different Dosing Regimens of Xeloda® in Combination With Taxotere® on Disease Progression in Patients With Locally Advanced and/or Metastatic Breast Cancer [NCT00077857] | Phase 2 | 470 participants (Actual) | Interventional | 2003-07-31 | Completed |
| Phase 2 Study of Adjuvant Chemotherapy With Docetaxel, Capecitabine and Cisplatin in Patients With Advanced Gastric Cancer [NCT00976976] | Phase 2 | 46 participants (Actual) | Interventional | 2007-05-31 | Completed |
| 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 2 | 37 participants (Anticipated) | Interventional | 2009-09-30 | Recruiting |
| Low Molecular Weight Heparin in Advanced Non Small Cell Lung Cancer (NSCLC): a Randomized Open Label Phase III Study Evaluating the Effect of Enoxaparin (Clexane) on Survival and Symptom Control in Patients With Stage IIIB and IV NSCLC Undergoing a Cispla [NCT00771563] | Phase 3 | 104 participants (Actual) | Interventional | 2008-06-30 | Completed |
| Randomized Proteomic Stratified Phase III Study of Second-Line Erlotinib Versus Chemotherapy in Patients With Inoperable Non Small Cell Lung Cancer [NCT00989690] | Phase 3 | 275 participants (Anticipated) | Interventional | 2008-02-29 | Recruiting |
| Evaluation of Differing Taxanes/Taxane Combinations on the Outcome of Patients With Operable Breast Cancer [NCT00050167] | Phase 1 | 603 participants (Actual) | Interventional | 2002-11-30 | Completed |
| A Phase II Study of Pre-operative Docetaxel for Progressive Localized Castration Resistant Prostate Cancer [NCT00811031] | Phase 2 | 0 participants (Actual) | Interventional | | Withdrawn |
| Phse II Study of Induction Chemotherapy With TPF Regimen Followed by Concurrent Chemoradiotherapy for Locally Advanced Nasopharyngeal Carcinoma [NCT00817583] | Phase 2 | 100 participants (Anticipated) | Interventional | 2009-01-31 | Not yet recruiting |
| An Explorative Study Of The Tolerability Of SU011248 In Combination With Docetaxel And Trastuzumab As First-Line Treatment In Patients With Breast Cancer Over-Expressing HER-2 [NCT00372424] | Phase 1 | 26 participants (Actual) | Interventional | 2006-12-31 | Completed |
| A Randomized Phase II Study of Docetaxel in Combination With Oxaliplatin With or Without 5-FU or Capecitabine in Metastatic or Locally Recurrent Gastric Cancer Previously Untreated With Chemotherapy for Advanced Disease [NCT00382720] | Phase 2 | 275 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Retrospective Analysis of Salvage Therapy With Bevacizumab Plus Docetaxel and Cisplatin for Taiwanese Metastatic Breast Cancer [NCT01025349] | Phase 2 | 20 participants (Actual) | Interventional | 2005-01-31 | Completed |
| Phase II Study Evaluating the Efficacy and Tolerance of Bevacizumab (Avastin) in HER2- Inflammatory Breast Cancer [NCT00820547] | Phase 2 | 100 participants (Actual) | Interventional | 2009-01-31 | Completed |
| A Randomized, Open-Label, Controlled, Phase II Trial of Combination Chemotherapy With or Without Panitumumab as First-line Treatment of Subjects With Metastatic or Recurrent Head and Neck Cancer, and Cross-over Second-line Panitumumab Monotherapy of Subje [NCT00454779] | Phase 2 | 113 participants (Actual) | Interventional | 2007-01-01 | Completed |
| Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Docetaxel and S-1 in Breast Cancer [NCT00994968] | Phase 2 | 49 participants (Anticipated) | Interventional | 2009-07-31 | Recruiting |
| 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 1 | 102 participants (Actual) | Interventional | 2005-12-31 | Completed |
| A Pilot Trial of Sequential Primary (Neoadjuvant) Combination Chemotherapy With Docetaxel/Capecitabine (TX) and Doxorubicin/Cyclophosphamide (AC) in Primary Breast Cancer With Evaluation of Chemotherapy Effects on Gene Expression [NCT00005908] | Phase 2 | 30 participants (Actual) | Interventional | 2000-06-30 | Completed |
| A Safety and Efficacy Study of Doxil and Taxotere ± Herceptin in Advanced Breast Cancer [NCT00004888] | Phase 2 | 84 participants (Actual) | Interventional | 2001-01-31 | Completed |
| Phase II Trial of Taxotere and Oxaliplatin Combination Chemotherapy in Squamous Cell Carcinoma of the Head and Neck [NCT00184028] | Phase 2 | 12 participants (Actual) | Interventional | 2004-09-30 | Terminated(stopped due to Insufficient Accrual) |
| Phase II Study of Irinotecan and Docetaxel in Patients With Metastatic or Unresectable Gastric or Gastroesophageal Junction Adenocarcinoma [NCT00183872] | Phase 2 | 40 participants (Actual) | Interventional | 2005-04-14 | Completed |
| Randomized, Placebo-Controlled, Double-Blind, Phase 2 Study Of AG-013736 In Combination With Docetaxel Versus Docetaxel Alone In Patients With Metastatic Breast Cancer Preceded By A Phase 1 Evaluation Of The Combination [NCT00076024] | Phase 1/Phase 2 | 174 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Primary Systemic Therapy Using Sequential Docetaxel/Cyclophosphamide/Bevacizumab Followed by Doxorubicin in Operable/Locally Advanced Breast Cancer [NCT00203502] | Phase 2 | 40 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Randomized Phase III Study of Docetaxel Versus Intercalated Erlotinib Docetaxel Combination Therapy in Patients With Relapsed EGFR (Epidermal Growth Factor Receptor) Wild Type, ALK(Anaplastic Lymphoma Kinase) Negative Non Squamous Cell Carcinoma. (NVALT [NCT02775006] | Phase 3 | 45 participants (Actual) | Interventional | 2016-10-14 | Terminated(stopped due to accrual to slow, target not achievable) |
| Phase II Study of Biweekly Gemcitabine and Docetaxel as First Line Treatment for Advanced Disease in Elderly Non Small Cell Lung Cancer (NSCLC) Patients. [NCT00905983] | Phase 2 | 48 participants (Actual) | Interventional | 2007-10-31 | Active, not recruiting |
| Phase II Study of Biweekly Gemcitabine and Docetaxel as First Line Therapy for Advanced Non-Small Cell Lung Cancer Patients With ECOG PS 2 [NCT00906061] | Phase 2 | 76 participants (Anticipated) | Interventional | 2007-10-31 | Recruiting |
| A Randomized Phase II Study of TAK228 (MLN0128, Sapanisertib) Plus Docetaxel Versus Standard of Care in Patients With Previously - Treated NFE2L2 or KEAP1-Positive Stage IV or Recurrent Squamous Cell Lung Cancer (ECOG-ACRIN LUNG-MAP Sub-Study) [NCT04267913] | Phase 2 | 0 participants (Actual) | Interventional | 2020-09-05 | Withdrawn(stopped due to The pharmaceutical company sold the compound and pulled out.) |
| Docetaxel in Patients With Metastatic Breast Cancer Who Have Been Heavily Pretreated, Including Prior Treatment With Paclitaxel or Docetaxel. [NCT02041351] | Phase 2 | 17 participants (Actual) | Interventional | 2013-11-30 | Completed |
| A Randomized, Crossover Phase 1 Study to Evaluate the Effects of Pevonedistat on the QTc Interval in Patients With Advanced Solid Tumors [NCT03330106] | Phase 1 | 68 participants (Actual) | Interventional | 2017-11-15 | Completed |
| Phase II-III Trial of Adjuvant Radiotherapy Following Radical Prostatectomy With or Without Adjuvant Docetaxel [NCT03070886] | Phase 2/Phase 3 | 175 participants (Actual) | Interventional | 2017-01-16 | Active, not recruiting |
| A Randomized, Double-Blind, Active Comparator, Non-Inferiority Study of Subcutaneously Administered Neugranin (Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor) or Pegfilgrastim in Subjects With Breast Cancer Receiving Myelosuppressiv [NCT01126190] | Phase 3 | 381 participants (Actual) | Interventional | 2010-06-30 | Completed |
| Phase II Trial Assessing Neoadjuvant Therapy With FEC 100 Followed by Taxotere® (Docetaxel) Plus Vectibix® (Panitumumab) in Patients With Operable, HR and Her-2 Negative Breast Cancer. TVA Study [NCT00933517] | Phase 2 | 62 participants (Actual) | Interventional | 2009-09-30 | Completed |
| A Phase III, Randomized, Multicenter, Open-Label, Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Patients [NCT03493854] | Phase 3 | 500 participants (Actual) | Interventional | 2018-06-14 | Completed |
| A Phase III Randomized Trial for Evaluating Second Line Hormonal Therapy (Ketoconazole/Hydrocortisone) Versus Paclitaxel/Estramustine Combination Chemotherapy on Progression Free Survival in Asymptomatic Patients With a Rising PSA After Hormonal Therapy f [NCT00027859] | Phase 3 | 0 participants | Interventional | 2003-10-08 | Completed |
| A Phase II Trial of Docetaxel and Carboplatin in Patients With Advanced Squamous Carcinoma of the Esophagus [NCT00003864] | Phase 2 | 0 participants | Interventional | 1999-09-03 | Completed |
| A Phase II Study of Gemcitabine and Docetaxel in Pancreatic Adenocarcinoma [NCT00003810] | Phase 2 | 0 participants | Interventional | 1999-08-11 | Completed |
| Phase III Study of Adriamycin/Taxotere Versus Adriamycin/Cytoxan for the Adjuvant Treatment of Node Positive or High Risk Node Negative Breast Cancer [NCT00003519] | Phase 3 | 2,778 participants (Anticipated) | Interventional | 1998-08-20 | Completed |
| FDG-PET Based Chemotherapy Selection for Metastatic Non-Small Cell Lung Cancer [NCT00564733] | Phase 2 | 55 participants (Actual) | Interventional | 2007-10-31 | Completed |
| 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 2 | 7 participants (Actual) | Interventional | 2019-01-24 | Terminated(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.) |
| Phase II Study of Oxaliplatin / Irinotecan / Bevacizumab Followed by Docetaxel / Bevacizumab in Inoperable Locally Advanced or Metastatic Gastric Cancer Patients [NCT00952003] | Phase 2 | 40 participants (Actual) | Interventional | 2009-07-31 | Completed |
| A Pilot Study of Taxotere (Docetaxel) Combined With Xeloda (Capecitabine) in the Treatment of Metastatic Breast Cancer [NCT00214864] | Phase 2 | 18 participants (Actual) | Interventional | 2002-12-31 | Completed |
| A Phase II, Prospective, Open-label Clinical Trial of Pre-Operative PD-1 Antibody (Toripalimab) + Chemoradiotherapy in Patients With Locally Advanced Esophageal Cancer [NCT04177875] | Phase 2 | 44 participants (Anticipated) | Interventional | 2019-05-01 | Recruiting |
| Multicentre, Randomised, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral SHR1020 Plus Docetaxel Therapy Compared to Placebo Plus Docetaxel Therapy in Patients With Local Advanced or Metastatic or Recurrent Non Squamous Non Sma [NCT02766140] | Phase 3 | 12 participants (Actual) | Interventional | 2016-06-30 | Terminated(stopped due to difficulty in recruitment) |
| Aromatase Inhibitors (AI) Plus Chemotherapy Versus Chemotherapy as Neoadjuvant Treatment in Postmenopausal Hormone Receptor-positive Breast Cancer [NCT02769104] | Phase 3 | 120 participants (Anticipated) | Interventional | 2016-05-31 | Recruiting |
| Multicentric, Randomized Phase II Trial for the Treatment of Patients With Relapsed Osteosarcoma [NCT02718482] | Phase 2 | 7 participants (Actual) | Interventional | 2016-04-06 | Terminated(stopped due to Not adequate enrollment (sample size not possible to reach)) |
| A Prospective, Randomized, Open, Multi-center Phase III Clinical Study Comparing Efficacy and Safety of Sequential T-FEC and TX-XEC as Post-operative Adjuvant Chemotherapy Options for the Treatment of Triple-negative Breast Cancer [NCT01642771] | Phase 3 | 636 participants (Anticipated) | Interventional | 2012-06-30 | Active, not recruiting |
| Randomized Phase II Study of Docetaxel Versus Cabazitaxel Post Abiraterone or Enzalutamide Progression [NCT03764540] | Phase 2 | 214 participants (Anticipated) | Interventional | 2019-04-01 | Recruiting |
| Study of Endostar Combined With Docetaxel and Cisplatin on the Angiogenesis of Advanced Non-small Cell Lung Cancer [NCT00657423] | Phase 3 | 80 participants (Anticipated) | Interventional | 2008-04-30 | Recruiting |
| A Multicenter Randomized Phase III Study Comparing 6 Versus 12 Months of Trastuzumab in Combination With Dose Dense Docetaxel Following FE75C as Adjuvant Treatment of Women With Axillary Lymph Node Positive Breast Cancer Over-expressing HER2 [NCT00615602] | Phase 3 | 489 participants (Actual) | Interventional | 2004-10-31 | Completed |
| A Multicenter, Open Label, Phase II Trial Evaluating Docetaxel (Taxotere®) + Anthracycline (Epirubicin or Doxorubicin) x 4 Cycles Followed by Docetaxel (T) Single Agent x 4 Cycles as First-Line Therapy in Patients With Her2 Negative Locally Advanced or Me [NCT00620100] | Phase 2 | 2 participants (Actual) | Interventional | 2004-09-30 | Terminated(stopped due to the study was early terminated due to lack of recruitment.) |
| A 2-part Trial Comparing Overall Survival of Patients With Metastatic Ewing's Sarcoma Treated With Vigil Versus Gemcitabine and Docetaxel and to Determine Safety Profile of Vigil in Combination With Irinotecan and Temozolomide. [NCT02511132] | Phase 2 | 22 participants (Actual) | Interventional | 2016-02-10 | Completed |
| A Multicenter Randomized Double-blinded Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of SCT-I10A or Placebo Plus Docetaxel in Treating Advanced Squamous Non-small Cell Lung Cancer [NCT04171284] | Phase 3 | 360 participants (Anticipated) | Interventional | 2019-10-22 | Active, not recruiting |
| Nedaplatin Versus Cisplatin in Induction Chemotherapy Combined With Concurrent Chemoradiotherapy for Locally Advanced Nasopharyngeal Carcinoma：a Prospective, Parallel, Randomized, Open Labeled, Phase III Non-Inferiority Clinical Study [NCT04437329] | Phase 3 | 352 participants (Anticipated) | Interventional | 2020-08-01 | Recruiting |
| Phase II, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy of AZD6244 in Combination With Docetaxel, Compared With Docetaxel Alone, in 2nd Line Patients With KRAS Mutation Positive Locally Advanced Metastatic NSCLC [NCT00890825] | Phase 2 | 88 participants (Actual) | Interventional | 2009-04-20 | Completed |
| An Open-Label, Randomized, Phase II/III Trial of Taxane Therapy With or Without Bavituximab for the Treatment of HER2-Negative Metastatic Breast Cancer [NCT02651610] | Phase 2/Phase 3 | 0 participants (Actual) | Interventional | 2015-12-31 | Withdrawn |
| Phase II Study: Induction Chemotherapy Followed by Transoral Robotic Surgery and Neck Dissection for Definitive Management of Oropharyngeal Squamous Cell Carcinoma. (NECTORS Trial) [NCT04277858] | Phase 2 | 60 participants (Anticipated) | Interventional | 2018-08-14 | Recruiting |
| A Randomized Phase II Trial of Docetaxel, Cisplatin, and Hypofractionated Radiotherapy Versus Docetaxel and Cisplatin for Limited Volume Stage IV Non-small Cell Lung Cancer: The Synergistic Metastases Annihilation With Radiotherapy and Docetaxel (Taxotere [NCT00887315] | Phase 2 | 11 participants (Actual) | Interventional | 2009-04-30 | Terminated(stopped due to Slow accrual and loss of sponsor) |
| "A Feasibility Trial of Partial Breast Irradiation With Various Concurrent Chemotherapy Regimens (PBIC)" [NCT00681993] | | 35 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Phase II Trial of Combined Modality Therapy With Growth Factor Support in Locally Advanced NSCLC [NCT00682383] | Phase 2 | 26 participants (Actual) | Interventional | 2003-09-30 | Completed |
| A Phase I/II Study Of The Docetaxel/Pemetrexed Combination As First Line Treatment In Patients With Advanced/Metastatic NSCLC [NCT00684099] | Phase 1/Phase 2 | 70 participants (Anticipated) | Interventional | 2006-05-31 | Completed |
| A Phase II Study of Pemetrexed Plus Cisplatin With Concurrent Radiation Therapy Followed by Every-21-Day Docetaxel Consolidation in Patients With Inoperable Stage IIIA/B Squamous Cell Lung Cancer [NCT02787473] | Phase 2 | 54 participants (Anticipated) | Interventional | 2016-10-31 | Recruiting |
| PErsonalized TREatment of High-risk MAmmary Cancer - the PETREMAC Trial [NCT02624973] | Phase 2 | 200 participants (Actual) | Interventional | 2016-04-15 | Active, not recruiting |
| A Neo-Adjuvant Study of Sequential Epirubicin and Docetaxel in Combination With Capecitabine in Patients With Locally Advanced Breast Cancer [NCT00645866] | Phase 2 | 47 participants (Anticipated) | Interventional | 2003-04-30 | Completed |
| A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability Study of INCB054828 in Subjects With Advanced Malignancies (FIGHT-101) [NCT02393248] | Phase 1/Phase 2 | 201 participants (Actual) | Interventional | 2015-02-27 | Terminated |
| Postoperative Concurrent Chemoradiotherapy in Treating Patients With High-Risk Malignant Salivary Gland Tumors of Head and Neck, A Non-Randomized, Phase II Trial [NCT02776163] | Phase 2 | 53 participants (Anticipated) | Interventional | 2016-06-01 | Recruiting |
| Phase II Study of Nimotuzumab Plus Docetaxel in Chemotherapy-refractory/Resistant Patients With Advanced Non-small-cell Lung Cancer [NCT00983047] | Phase 2 | 30 participants (Actual) | Interventional | 2009-08-31 | Terminated(stopped due to The sponsor decide to terminate) |
| Evaluation of Bevacizumab and Weekly Docetaxel in Elderly (≥ 75 Years) Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00541099] | Phase 2 | 11 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Bioequivalence Study of Docetaxel for Injectable Emulsion (ANX-514) in Patients With Advanced Cancer [NCT00664170] | Phase 1 | 39 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Phase II Single Center Study of Docetaxel for Clinically Asymptomatic High Risk Prostate Cancer Patients With an Early Rising PSA Following Radical Prostatectomy [NCT00714376] | Phase 2 | 6 participants (Actual) | Interventional | 2008-05-31 | Terminated(stopped due to Prematurely terminated due to financial considerations) |
| A Phase II Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, Erlotinib, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck [NCT00720304] | Phase 2 | 37 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Phase II Study: Docetaxel Plus Oxaliplatin as Second-line Therapy in Patients With Advanced Metastatic Pancreatic Cancer [NCT00690300] | Phase 2 | 44 participants (Anticipated) | Interventional | 2008-01-31 | Recruiting |
| A Phase II Multicenter Study of Docetaxel and Oxaliplatin in Combination With Bevacizumab as First-Line Treatment in Chemotherapy-Naïve Subjects With Unresectable Locally Advanced and/or Recurrent (Stage IIIB) or Metastatic (Stage IV) Non-Squamous Cell Hi [NCT00356122] | Phase 2 | 53 participants (Actual) | Interventional | 2006-07-31 | Completed |
| A Phase II Open-Label Study Designed to Evaluate the Efficacy and Safety, of Erlotinib in Combination With Docetaxel in Selected Non Small Cell Lung Cancer Patients Eligible for First Line Treatment [NCT00840125] | Phase 2 | 4 participants (Actual) | Interventional | 2009-02-28 | Completed |
| A Phase I/II Study of Docetaxel, 5-Fluorouracil and Oxaliplatin (D-FOX) in Patients With Untreated Locally Unresectable or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction [NCT00526110] | Phase 1/Phase 2 | 98 participants (Actual) | Interventional | 2004-08-31 | Completed |
| A Phase III, Randomised, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of 10 mg ZD4054 (Zibotentan) in Combination With Docetaxel in Comparison With Docetaxel in Patients With Metastatic Hormone-resistant Prostate Cancer [NCT00617669] | Phase 3 | 1,494 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Phase 1 Dose Finding Study of the gFOLFOXIRITAX Regimen Using UGT1A1 Genotype-directed Irinotecan With Fluorouracil, Leucovorin, Oxaliplatin and Taxotere in Patients With Untreated Advanced Upper Gastrointestinal Adenocarcinomas: The I-FLOAT Study [NCT04361708] | Phase 1 | 54 participants (Anticipated) | Interventional | 2020-05-08 | Recruiting |
| Adjuvant 3DCRT/IMRT in Combination With Androgen Suppression and Docetaxel for High Risk Prostate Cancer Patients Post-Prostatectomy: A Phase II Trial [NCT00528866] | Phase 2 | 80 participants (Actual) | Interventional | 2008-04-30 | Completed |
| 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 3 | 260 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Randomized, Open-label, Phase 3 Study of MK-2870 vs Chemotherapy (Docetaxel or Pemetrexed) in Previously Treated Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With EGFR Mutations or Other Genomic Alterations [NCT06074588] | Phase 3 | 556 participants (Anticipated) | Interventional | 2023-11-12 | Recruiting |
| A Randomized Phase II Study of ADT + Abiraterone Versus ADT + Docetaxel + Abiraterone in Patients With Low Volume Metastatic Hormone Sensitive Prostate Cancer [NCT06060587] | Phase 2 | 150 participants (Anticipated) | Interventional | 2023-10-19 | Recruiting |
| 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 2 | 610 participants (Anticipated) | Interventional | 2021-09-16 | Recruiting |
| A Phase III, Randomized, Double-Blind, Clinical Trial of Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) Versus Placebo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Subjects With Gastric and Gastroesophageal Junction (GEJ) Adeno [NCT04882241] | Phase 3 | 120 participants (Anticipated) | Interventional | 2020-07-29 | Active, 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 3 | 686 participants (Anticipated) | Interventional | 2020-09-18 | Recruiting |
| A Phase 2, Randomized, Open-label Three-arm Clinical Study to Evaluate the Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care Chemotherapy and Lenvatinib Monotherapy in Participants With R [NCT04428151] | Phase 2 | 400 participants (Anticipated) | Interventional | 2020-08-06 | Recruiting |
| A Multinational, Multicenter, Phase III, Randomized Open-label Trial of Pembrolizumab Versus Docetaxel in Previously Treated Subjects With Non-Small Cell Lung Cancer [NCT02864394] | Phase 3 | 425 participants (Actual) | Interventional | 2016-09-07 | Completed |
| Randomized Phase II/III Trial of Adjuvant Radiation Therapy With Cisplatin, Docetaxel-Cetuximab, or Cisplatin-Atezolizumab in Pathologic High-Risk Squamous Cell Cancer of the Head and Neck [NCT01810913] | Phase 2/Phase 3 | 613 participants (Anticipated) | Interventional | 2013-03-22 | 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 3 | 4,804 participants (Actual) | Interventional | 2011-11-08 | Active, not recruiting |
| A Phase II Trial of Licorice Root and Docetaxel in Patients With Hormone Refractory Prostate Cancer [NCT00176631] | Phase 2 | 10 participants (Actual) | Interventional | 2007-09-30 | Terminated(stopped due to slow accrual) |
| "A Phase IIA Study of Sequential (First Strike, Second Strike) Therapies, Modeled on Evolutionary Dynamics of Anthropocene Extinctions, for High Risk Metastatic Castration Sensitive Prostate Cancer" [NCT05189457] | Phase 2 | 31 participants (Anticipated) | Interventional | 2022-01-25 | Recruiting |
| Phase III Clinical Study of SI-B001 Combined With Docetaxel Second-line Therapy in Patients With Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma Without Actionable Genomic Alterations Who Failed Only First-line Treatment With PD-1/PD-L [NCT05943795] | Phase 3 | 584 participants (Anticipated) | Interventional | 2023-07-14 | Recruiting |
| Randomized, Placebo-Controlled, Phase 2 Study Of Induction Chemotherapy With Cisplatin/Carboplatin, And Docetaxel With Or Without Erlotinib In Patients With Head And Neck Squamous Cell Carcinomas Amenable For Surgical Resection [NCT01927744] | Phase 2 | 105 participants (Anticipated) | Interventional | 2013-12-16 | Recruiting |
| Neoadjuvant Chemotherapy With Docetaxel, Cisplatin Followed by Maintenance Therapy With the EGFR Inhibitor Erlotinib (Tarceva) in Patients With Stage I, II and III Non-Small Cell Lung Cancer Following Definitive Surgical Resection [NCT00254384] | Phase 1 | 50 participants (Actual) | Interventional | 2005-10-05 | Active, not recruiting |
| Phase I, Open Label, Dose Escalation Study of the Safety, Tolerability, and Pharmacokinetics of the Combination RAD001 Plus Docetaxel in Patients With Metastatic Breast Cancer [NCT00253318] | Phase 1 | 15 participants (Actual) | Interventional | 2005-11-01 | Terminated(stopped due to Toxicity and Lack of Efficacy) |
| Phase III Trial of Laryngeal Preservation Comparing Induction Chemotherapy With Cisplatin, 5-fluorouracil and Docetaxel (TPF) Followed by Radiotherapy and Concomitant Administration of Radiotherapy With Cisplatin [NCT03340896] | Phase 3 | 256 participants (Actual) | Interventional | 2015-06-25 | Active, not recruiting |
| A Phase III, Randomized, Double-Blind, Clinical Trial of Pembrolizumab (MK-3475) Plus Chemotherapy (XP or FP) Versus Placebo Plus Chemotherapy (XP or FP) as Neoadjuvant/Adjuvant Treatment for Subjects With Gastric and Gastroesophageal Junction (GEJ) Adeno [NCT03221426] | Phase 3 | 1,007 participants (Actual) | Interventional | 2017-10-09 | Active, not recruiting |
| Phase II Study of the Early Use of Docetaxel in Patients With Biochemical Relapse After Primary Therapy for Prostate Cancer and an Incomplete Response to Androgen Deprivation Therapy. [NCT00482274] | Phase 2 | 3 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to Drug supplier stopped funding due to loss of study drug (docetaxel) patent.) |
| A Phase II Study of Neoadjuvant Bevacizumab Plus Docetaxel in High Risk Patients With Prostate Cancer Undergoing Radical Prostatectomy [NCT00321646] | Phase 2 | 42 participants (Actual) | Interventional | 2006-06-30 | Completed |
| A Phase I/II Study of Azacitidine (Vidaza), Docetaxel and Prednisone for Patients With Hormone Refractory Metastatic Prostate Cancer Previously Treated With a Taxotere Containing Regimen. [NCT00503984] | Phase 1/Phase 2 | 22 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to Withdrawal of Funding) |
| Phase II Study of Neoadjuvant Treatment With NOV-002 in Combination With Doxorubicin and Cyclophosphamide Followed by Docetaxel in Patients With Stages IIB-IIIC Breast Cancer [NCT00499122] | Phase 2 | 41 participants (Actual) | Interventional | 2007-06-04 | Completed |
| A Randomized Phase 3 Study Of Docetaxel In Combination With Sunitinib Versus Docetaxel In The First-Line Treatment Of Advanced Breast Cancer Patients [NCT00393939] | Phase 3 | 594 participants (Actual) | Interventional | 2007-02-28 | Completed |
| A Randomized Phase II Study of Intermittent Chemotherapy or Intermittent Chemotherapy With Maintenance GM-CSF in Patients With Previously Untreated Hormone Refractory Prostate Cancer [NCT00488982] | Phase 2 | 125 participants (Actual) | Interventional | 2007-04-30 | Completed |
| Phase II Prospective Study Evaluating the Role of Personalized Chemotherapy Regimens for Chemo-Naive Select Stage IIIB and IV Non-Small Cell Lung Cancer (NSCLC) in Patients Using a Genomic Predictor of Platinum Resistance to Guide Therapy [NCT00509366] | Phase 2 | 101 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to Study terminated due to reproducibility issues with genomics prediction model.) |
| A Randomized, Double-Blinded, Placebo-Controlled, Phase 2 Study With and Without Enzastaurin in Combination With Docetaxel and Prednisone, Followed By Enzastaurin Maintenance as First-Line Treatment in Hormone Refractory Metastatic Prostate Cancer Patient [NCT00466440] | Phase 2 | 108 participants (Actual) | Interventional | 2007-06-30 | Completed |
| "Phase II Study of TPF Induction Chemotherapy Followed by Hyperfractionated Radiotherapy With Cetuximab Boost Concomitant With Cetuximab in Patients With Local Advanced Larynx/Hypolarynx Carcinoma" [NCT00941135] | Phase 2 | 70 participants (Anticipated) | Interventional | 2009-05-31 | Terminated |
| Docetaxel, Carboplatin, Trastuzumab and Bevacizumab (TCH+B) For Early-Stage HER-2/Neu(+) Breast Cancer and Bone Marrow Micrometastases [NCT00949247] | Early Phase 1 | 20 participants (Actual) | Interventional | 2009-12-31 | Completed |
| PROMIX - Preoperative Treatment of Breast Cancer With a Combination of Epirubicin, Docetaxel and Bevacizumab. A Translational Trial on Molecular Markers and Functional Imaging to Predict Response Early. A Phase 2 Study. [NCT00957125] | Phase 2 | 151 participants (Actual) | Interventional | 2008-09-30 | Active, not recruiting |
| A Phase I/II Study of RAD001 With Docetaxel in the Treatment of Metastatic, Androgen Independent Prostate Cancer [NCT00459186] | Phase 1/Phase 2 | 19 participants (Actual) | Interventional | 2005-11-30 | Completed |
| Title: A Pilot Study Evaluating the Safety and Feasibility of Custirsen (OGX-011) in Combination With Second Line Chemotherapy in Patients With Hormone Refractory Prostate Cancer [NCT00327340] | Phase 2 | 70 participants (Actual) | Interventional | 2006-07-31 | Completed |
| A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Pro [NCT03933449] | Phase 3 | 123 participants (Actual) | Interventional | 2016-12-29 | Completed |
| A Randomized Phase II Study of Docetaxel vs. Docetaxel Plus Cisplatin vs. Docetaxel Plus S-1 as Second-line Chemotherapy After Cisplatin Plus S-1 or Capecitabine in Metastatic Gastric Cancer [NCT00980603] | Phase 2 | 144 participants (Anticipated) | Interventional | 2008-11-30 | Recruiting |
| A Randomized Phase II Study of Weekly or Every 3 Weeks ABI-007 Versus Every 3 Weeks Taxotere as First Line Therapy of Stage IV (Metastatic) Breast Cancer [NCT00274456] | Phase 2 | 302 participants (Actual) | Interventional | 2005-11-01 | Completed |
| A Pilot, Phase II, Multicenter, Open-Label, Prospective Evaluation of Docetaxel and Bevacizumab ± Trastuzumab in the First-Line Treatment of Patients With Metastatic Breast Cancer [NCT00364611] | Phase 2 | 73 participants (Actual) | Interventional | 2006-08-31 | Completed |
| A Phase II, Multicenter Evaluation of Docetaxel, Gemcitabine, and Bevacizumab Combination Followed by Bevacizumab Alone in Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00378573] | Phase 2 | 17 participants (Actual) | Interventional | 2007-01-31 | Terminated(stopped due to Incidence of GI Perforation) |
| Phase II Study of Salvage Therapy With Sunitinib,Docetaxel and Platinum on Metastatic or Unresectable Non Small Cell Lung Cancer [NCT01019798] | Phase 2 | 16 participants (Anticipated) | Interventional | 2009-01-31 | Recruiting |
| To Evaluate the Cardiac Safety of Pegylated Liposomal Doxorubicin Concurrently Plus Trastuzumab and Pertuzumab in the Adjuvant Setting for Early-stage HER-2-positive Breast Cancer: a Multicenter, Randomized Controlled Clinical Study [NCT05656079] | | 204 participants (Anticipated) | Interventional | 2021-07-01 | Recruiting |
| TNM Trial: Upfront Docetaxel [T] and Alternating iv and Oral Vinorelbine [N] Followed, by Either Maintenance Oral Vinorelbine, or Observation for Advanced Breast Cancer [NCT02144194] | Phase 2 | 65 participants (Actual) | Interventional | 2012-03-31 | Active, not recruiting |
| Pharmacodynamic Study Using FLT-PET/CT in Patients With Advanced Solid Malignancies Treated With a Sequential Combination of X-82 and Docetaxel [NCT02146222] | Phase 1 | 14 participants (Actual) | Interventional | 2014-09-30 | Completed |
| 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) | Observational | 2021-07-31 | Recruiting |
| A Phase III Trial for Locally Recurrent, Previously Irradiated Head and Neck Cancer: Concurrent Re-Irradiation and Chemotherapy Versus Chemotherapy Alone [NCT00113399] | Phase 3 | 15 participants (Actual) | Interventional | 2005-04-30 | Terminated(stopped due to Terminated early due to low accrual.) |
| Infusional Fluorouracil and Weekly Docetaxel as First-line Therapy for Gastric Cancer With Bone Marrow Metastasis and Disseminated Intravascular Coagulation: a Multi-center, Phase II Trail [NCT04547153] | Phase 2 | 24 participants (Actual) | Interventional | 2021-01-15 | Completed |
| Phase I/II Study of Oral S-1 Plus Docetaxel in Elderly Patients With Advanced Gastric Cancer [NCT00209729] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2005-04-30 | Suspended(stopped due to Registration is less) |
| 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 2 | 49 participants (Actual) | Interventional | 2003-10-31 | Completed |
| A Randomized Phase 2, Open-Label Study Of CP-751,871 In Combination With Docetaxel And Docetaxel Alone As A First Line Treatment Of Patients With Advanced Breast Cancer [NCT00678626] | Phase 2 | 0 participants (Actual) | Interventional | 2009-04-30 | Withdrawn |
| Randomized Phase 3 Trial of Triple Combination of Induction, Concurrent and Adjuvant Chemotherapy Versus Concurrent Chemotherapy Alone in High Risk Nasopharyngeal Carcinoma Patients Treated With Intensity-modulated Radiotherapy [NCT02621970] | Phase 3 | 534 participants (Anticipated) | Interventional | 2016-01-31 | Not yet recruiting |
| A Randomized Phase II, Multi-Center, Open-Label Trial of PR104 and Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer [NCT00862134] | Phase 2 | 42 participants (Actual) | Interventional | 2009-03-31 | Terminated(stopped due to Interim analysis indicated low probability of clinically significant result) |
| A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06939999 (PRMT5 INHIBITOR) IN PARTICIPANTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER, HEAD AND NECK SQUAMOUS CELL CARCINOMA, ESOPHAGEAL C [NCT03854227] | Phase 1 | 54 participants (Actual) | Interventional | 2019-03-14 | Terminated(stopped due to The study has been terminated based on a strategic evaluation within the current Pfizer oncology portfolio. This decision is not due to any safety concerns or requests from any regulatory authorities.) |
| A Phase III Randomised Study Comparing Three Combination Chemotherapy Regimens in Patients With Non Pre-treated Advanced Non-small Cell Lung Cancer [NCT00622349] | Phase 3 | 707 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Multicenter Phase II Study Evaluating Docetaxel and CDDP as Induction Regimen Prior to Surgery or Radiochemotherapy With Docetaxel, Followed by Adjuvant Docetaxel Therapy in Chemonaive Patients With NSCLC Stage II, IIIa and IIIb [NCT00432315] | Phase 2 | 80 participants (Actual) | Interventional | 2001-05-31 | Completed |
| Randomized Trial of Epirubicin and Cyclophosphamide Followed by Docetaxel Against Docetaxel and Cyclophosphamide in Patients With TOP2A Normal Early Breast Cancer [NCT00689156] | Phase 3 | 2,015 participants (Actual) | Interventional | 2008-06-30 | Completed |
| [NCT00833326] | Phase 1 | 27 participants (Actual) | Interventional | 2009-01-31 | Completed |
| Phase II Study for Inoperable Non-Metastatic Pancreatic Cancer (Stage IVA) With Neoadjuvant Gemzar, Taxotere and Xeloda (GTX), and Radiation With Gemzar [NCT00869258] | Phase 2 | 32 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Single Agent Chemotherapy With Weekly Docetaxel vs Combination Chemotherapy in Second-line Treatment of Advanced Non Small Cell Lung Cancer [NCT00345059] | Phase 3 | 84 participants (Actual) | Interventional | 2005-05-31 | Terminated(stopped due to slow accrual) |
| Pilot Phase II Study of Docetaxel in Combination With a Dietary Phytonutrient in First Line Treatment of Hormone Independent Metastatic Prostate Cancer [NCT01012141] | Phase 2 | 30 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Multicentre Study to Determine the Feasibility of Using an Integrated Consent Model to Compare Three Standard of Care Regimens for The Treatment of Triple-Negative Breast Cancer in the Neoadjuvant/Adjuvant Setting (REaCT-TNBC) OTT 15-04 [NCT02688803] | Phase 4 | 2 participants (Actual) | Interventional | 2016-08-31 | Completed |
| A Randomised Phase III Study of Trastuzumab-Docetaxel vs Trastuzumab-Vinorelbine as 1. Line Therapy for Patients With Metastatic HER2 Positive Breast Cancer [NCT00430001] | Phase 3 | 300 participants (Anticipated) | Interventional | 2005-05-31 | Recruiting |
| Phase I Study of Docetaxel and Temsirolimus in Resistant Solid Malignancies [NCT00703625] | Phase 1 | 26 participants (Actual) | Interventional | 2008-03-08 | Completed |
| An Open Label, Randomized Study of Neoadjuvant Nivolumab and Chemotherapy, With or Without Sub-ablative Stereotactic Body Radiation Therapy, for Resectable Stage IIA to IIIB Non-small Cell Lung Cancer [NCT05500092] | Phase 2 | 52 participants (Anticipated) | Interventional | 2023-01-25 | Recruiting |
| Nedaplatin/Docetaxel Versus Cisplatin/Docetaxel in Treatment of Advanced/Relapsed Squamous Cell Lung Cancer :A Randomized, Open, Parallel, Multicentre, Phase Ⅲ Study [NCT02643407] | Phase 3 | 488 participants (Anticipated) | Interventional | 2015-10-31 | Recruiting |
| Efficacy and Safety Study of TA(E)C-GP Versus A(E)C-T for the High Risk Triple-negative Breast Cancer Patients Predicted by the Messenger RNA (mRNA)-Long Non-coding RNA (lncRNA) Signature and Validation of the Signature's Efficacy [NCT02641847] | Phase 2/Phase 3 | 503 participants (Anticipated) | Interventional | 2015-07-31 | Recruiting |
| 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 1 | 77 participants (Actual) | Interventional | 2009-03-17 | Completed |
| The Efficacy of Sequential Intravesical Gemcitabine and Docetaxel Therapy (GEM/DOCE) in High-risk BCG-naive Patients With Non-muscle Invasive Bladder Cancer (NMIBC) [NCT05671900] | | 70 participants (Anticipated) | Interventional | 2020-04-01 | Active, not recruiting |
| Phase 2 Randomized Study of Adriamycin & Docetaxel in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor to Validate Gene Expression & Proteomic Signatures Predictive of Treatment Respons [NCT00669773] | Phase 2 | 49 participants (Actual) | Interventional | 2007-02-28 | Active, not recruiting |
| Prospective Non-inferiority Randomized Trial Comparing Clinical Target Volume Based on Disease Extension Risk Atlas and Computer-aided Delineation and Traditional Clinical Target Volume in Radiotherapy for Nasopharyngeal Carcinoma [NCT02627807] | | 386 participants (Actual) | Interventional | 2015-12-31 | Active, not recruiting |
| A Phase II Study of Docetaxel Plus Carboplatin in Chemonaive Hormone-Refractory Prostate Cancer (HRPC) Patients [NCT00675545] | Phase 2 | 2 participants (Actual) | Interventional | 2007-05-31 | Completed |
| A Prospective, Randomised, Double-Blind, Placebo-Controlled Phase III Study of Modafinil to Improve Fatigue and Quality of Life in Patients Treated With Docetaxel-Based Chemotherapy for Metastatic Breast or Prostate Cancer [NCT00917748] | Phase 3 | 84 participants (Actual) | Interventional | 2009-06-30 | Completed |
| Phase II Trial Of Oxaliplatin With Docetaxel Followed By Epidermal Growth Factor Antibody (EGFR-AB) Cetuximab In Patients With Recurrent Or Metastatic Squamous Cell Carcinoma of Head and Neck (SCCHN) [NCT00591149] | Phase 2 | 16 participants (Actual) | Interventional | 2007-06-30 | Terminated(stopped due to Study was stopped due to termination of funding) |
| 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 2 | 79 participants (Anticipated) | Interventional | 2022-08-22 | Recruiting |
| Open Label, Randomized, Single-dose, Crossover Study to Evaluate the Pharmacokinetics of Docetaxel Between Two Docetaxel Products, CKD-810 and Taxotere Inj., in Patients With Advanced Solid Cancer [NCT01019941] | Phase 1 | 44 participants (Anticipated) | Interventional | 2009-08-31 | Completed |
| 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 2 | 125 participants (Actual) | Interventional | 2008-10-31 | Terminated(stopped due to Withdrawal of funding support) |
| Phase I/II Trial of Weekly Docetaxel and Cisplatin for Locoregional Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT00268671] | Phase 1/Phase 2 | 45 participants | Interventional | 2003-08-31 | Completed |
| A Multi-center Phase II Study Evaluating the Efficacy and Tolerance of the Association of Liposomal Doxorubicin and Docetaxel in First Line Chemotherapy in Patients With Metastatic Breast Cancer [NCT00524810] | Phase 2 | 67 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (PIONeeR Clinical Study) [NCT03833440] | Phase 2 | 120 participants (Anticipated) | Interventional | 2019-10-08 | Recruiting |
| Comparative Analysis of the Efficacies of AT and AC-T Regimens in Neoadjuvant Chemotherapy of Breast Cancer [NCT02613026] | Phase 3 | 104 participants (Actual) | Interventional | 2009-07-31 | Completed |
| A Randomized Phase 2 Clinical Trial Of Docetaxel With Or Without PF-3512676 As First-Line Treatment Of Patients With Advanced Breast Cancer [NCT00471159] | Phase 2 | 0 participants (Actual) | Interventional | 2007-08-31 | Withdrawn |
| Induction Chemotherapy With Cetuximab, Docetaxel, Cisplatin, and Fluorouracil (ETPF) in Patient With Resectable Stage III-IV Squamous Cell Carcinoma of the Oropharynx [NCT00665392] | Phase 2 | 42 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Immunotherapy With Low Dose Interleukin-2 After Cytoreductive Chemotherapy for Patients With Hormone Refractory Metastatic Prostate Cancer: A Phase I/II Study [NCT00283829] | Phase 1/Phase 2 | 30 participants (Actual) | Interventional | 2002-09-30 | Completed |
| Randomized Phase II Study of Docetaxel in Combination With Zactima (ZD6474) in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT00459043] | Phase 2 | 30 participants (Actual) | Interventional | 2007-03-31 | Completed |
| PANTHER. A Randomized Phase 3 Study Comparing Biweekly and Tailored Epirubicin + Cyclophosphamide Followed by Biweekly Tailored Docetaxel (dtEC→dtT) Versus Three Weekly Epirubicin + Cyclophosphamide + 5-fluorouracil Followed by Docetaxel (FEC→T) in Lymph [NCT00798070] | Phase 3 | 2,017 participants (Actual) | Interventional | 2007-02-28 | Active, not recruiting |
| A Multicenter, Double-blind, Randomized, Parallel-group, Phase III Study of the Efficacy and Safety of QL1701 Plus Docetaxel Versus Herceptin® Plus Docetaxel as First Line Therapy in Patients With HER2-positive Metastatic Breast Cancer [NCT05629949] | Phase 3 | 474 participants (Actual) | Interventional | 2020-04-29 | Active, not recruiting |
| A Phase II Study of Neoadjuvant Therapy With Cisplatin, Docetaxel, Panitumumab Plus Radiation Therapy Followed by Surgery in Patients With Locally Advanced Adenocarcinoma of the Distal Esophagus [NCT00757172] | Phase 2 | 70 participants (Actual) | Interventional | 2009-01-31 | Completed |
| Phase I/II and Pharmacokinetic Study of Docetaxel Plus VEGF Trap (AVE0005, NSC# 724770) in Patients With Recurrent Ovarian, Primary Peritoneal, and Fallopian Tube Cancer [NCT00436501] | Phase 1/Phase 2 | 58 participants (Actual) | Interventional | 2007-01-31 | Completed |
| Apatinib Plus Docetaxel Versus Docetaxel as Second-line Treatment in Advanced Gastric Cancer Stage II Randomized Controlled Clinical Studies [NCT02596256] | Phase 2 | 80 participants (Anticipated) | Interventional | 2016-04-30 | Active, not recruiting |
| A Randomised,Multi-Center Study of Docetaxol Plus Capecitabine or Cisplatin in Anthracycline-Pretreated Patients With Advanced Breast Cancer [NCT00717951] | Phase 2 | 120 participants (Actual) | Interventional | 2008-05-31 | Active, not recruiting |
| Chemotherapy Induction and Chemoradiotherapy Combined With Cetuximab Respectively in Patients With Non-Metastatic Esophageal Carcinoma: A Multicentric Phase II Study [NCT00735345] | Phase 2 | 50 participants (Anticipated) | Interventional | 2008-08-31 | Terminated(stopped due to because of safety concerns the study was terminated prematurely) |
| Phase I-II Study of Liposomal Doxorubicin (Myocet®), Docetaxel and Trastuzumab as First-Line Treatment of Patients With HER-2/Neu Positive Metastatic Breast Cancer [NCT00250874] | Phase 2 | 45 participants | Interventional | 2003-12-31 | Recruiting |
| A Multicenter, Randomised Phase II Trial on the Therapy of Advanced Gastric Cancer or Adenocarcinoma of the Esophagogastric Junction in Patients Older Than 65 Years With Specific Regard of Quality of Life and Pharmacogenetic Risk Profile [NCT00737373] | Phase 2 | 143 participants (Actual) | Interventional | 2007-08-31 | Completed |
| A Randomized, Multicenter, Phase II Study of Docetaxel and TS-1 Combination as a First-line Treatment in Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma (HNSCC) [NCT00805012] | Phase 2 | 96 participants (Anticipated) | Interventional | 2008-12-31 | Terminated(stopped due to slow accrual rate) |
| Stereotactic Radiosurgery and Systemic Dose Chemotherapy for Locally Advanced Lung Cancer (Protocol Number GK001) [NCT02568033] | Early Phase 1 | 22 participants (Anticipated) | Interventional | 2013-10-31 | Recruiting |
| A Phase I/II Study of Taxotere, Oxaliplatin, and 5- Fluorouracil [NCT00711243] | Phase 1/Phase 2 | 59 participants (Actual) | Interventional | 2005-04-20 | Completed |
| Docetaxel Plus Bevacizumab in Pretreated, Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC [NCT00741195] | Phase 2 | 50 participants (Actual) | Interventional | 2008-04-30 | Completed |
| A Phase II Study of Pre-operative Chemotherapy Plus Bevacizumab With Early Salvage Therapy Based on PET Assessment of Response in Patients With Locally Advanced But Resectable Gastric and GEJ Adenocarcinoma [NCT00737438] | Phase 2 | 22 participants (Actual) | Interventional | 2008-08-31 | Completed |
| A Phase 2/3 Multicenter, Randomized, Double Blind Study of Docetaxel (Taxotere) Plus DN-101 or Placebo in Androgen Independent Prostate Cancer (AIPC) [NCT00043576] | Phase 2/Phase 3 | 250 participants | Interventional | 2002-08-31 | Active, not recruiting |
| Single Center Open-Label Non-Comparative Phase I Dose Finding Study Of Weekly Flavopiridol In Combination With Weekly Docetaxel In Patients With Advanced Solid Tumors [NCT00045448] | Phase 1 | 0 participants | Interventional | 2002-04-30 | Completed |
| Defining the Interaction of Docetaxel and Lonafarnib in Patients With Advanced Malignancies [NCT00288444] | Phase 1 | 38 participants (Actual) | Interventional | 2006-01-31 | Terminated |
| 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 2 | 162 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Multicenter Randomized Phase II Trial of Docetaxel With/Without VANDETANIB for Advanced Gastroesophageal Cancer [NCT00683787] | Phase 2 | 8 participants (Actual) | Interventional | 2008-05-31 | Terminated(stopped due to low accrual) |
| A Phase II Study of the Combination of Metronomic Docetaxel and Bevacizumab as 2nd Line Treatment in Patients With Small Cell Lung Cancer (SCLC) [NCT00755157] | Phase 2 | 0 participants (Actual) | Interventional | 2008-04-30 | Withdrawn |
| A Phase II Protocol in Borderline Resectable Pancreatic Cancer Using Gemcitabine/Docetaxel Chemotherapy and An Oxaliplatin-Based Chemoradiation. [NCT00761241] | Phase 2 | 40 participants (Anticipated) | Interventional | 2008-09-30 | Completed |
| A Pilot Study of Docetaxel (Taxotere), Vinorelbine, and Bevacizumab, as Adjuvant Chemotherapy for Patients With Resected Stage I-III Non-small Cell Lung Cancer [NCT00675597] | | 25 participants (Actual) | Interventional | 2008-05-31 | Completed |
| Multicenter Study on Efficacy and Safety of Concurrent and Adjuvant Chemotherapy With Cisplatin and Docetaxel Combined With Radiotherapy for Local Advanced Cervical Cancer [NCT02703961] | Phase 3 | 598 participants (Anticipated) | Interventional | 2016-02-29 | Recruiting |
| A Study of the Proper Dosage of Lovastatin and Docetaxel for Patients With Cancer [NCT00584012] | Phase 1 | 9 participants (Actual) | Interventional | 2004-04-30 | Terminated(stopped due to Funding issues) |
| A Phase 2 Study of Docetaxel, Ramucirumab, and Pembrolizumab for Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer Who Progressed on Platinum-Doublet and PD-1/PD-L1 Blockade [NCT04340882] | Phase 2 | 41 participants (Anticipated) | Interventional | 2020-06-05 | Recruiting |
| Phase II Study of a Biochemically Synergistic Regimen for Metastatic Pancreatic Cancer (Stage IVB) With Gemzar, Taxotere and Xeloda (GTX) [NCT00996333] | Phase 2 | 46 participants (Actual) | Interventional | 2003-06-30 | Completed |
| The Evaluation of Efficacy and Safety of Subsequent Cisplatin and Docetaxel Regimen In The First Line Treatment of Advanced Epithelial Ovarian Cancer [NCT00772863] | Phase 2 | 37 participants (Actual) | Interventional | 2003-09-30 | Completed |
| 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 2 | 90 participants (Actual) | Interventional | 2010-08-31 | Completed |
| Phase III Trial of Docetaxel vs. Docetaxel and Radium-223 for Metastatic Castration-Resistant Prostate Cancer (mCRPC) [NCT03574571] | Phase 3 | 738 participants (Anticipated) | Interventional | 2018-06-19 | Recruiting |
| Randomized Phase II Trial of Docetaxel With or Without PSA-TRICOM Vaccine in Patients With Castrate-Resistant Metastatic Prostate Cancer [NCT01145508] | Phase 2 | 10 participants (Actual) | Interventional | 2010-08-31 | Terminated(stopped due to Poor accrual) |
| A Randomised, Multicentre, Multinational Phase II Study to Evaluate Pertuzumab in Combination With Trastuzumab, Given Either Concomitantly or Sequentially With Standard Anthracycline-based Chemotherapy or Concomitantly With a Non-anthracycline-based Chemo [NCT00976989] | Phase 2 | 225 participants (Actual) | Interventional | 2009-11-30 | Completed |
| Phase II Trial of Docetaxel and Liposomal Doxorubicin (Doxil) Chemotherapy Combined With Enoxaparin in Patients With Advanced Pancreatic Cancer [NCT00426127] | Phase 2 | 2 participants (Actual) | Interventional | 2006-11-30 | Terminated(stopped due to Inadequate number of eligible patients) |
| Intensity-modulated Radiation Therapy Combined With Cisplatin-based or Carboplatin-based Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma：: A Phase 3 Trial [NCT03919552] | Phase 3 | 482 participants (Anticipated) | Interventional | 2018-01-31 | Recruiting |
| Docetaxel Combined With Pulsatile Erlotinib (Tarceva®) In Patients With Metastatic Non Small Cell Lung Cancer (NSCLC) (DOPERLO) [NCT00783471] | Phase 2 | 51 participants (Actual) | Interventional | 2008-11-30 | Terminated(stopped due to The low accrual rate of the study (30% of the expected accrual rate)/Low efficacy in both treatment arms.) |
| CADENCE: Carboplatin and Docetaxel in Neoadjuvant Treatment of ER-Negative, HER2-Negative Breast Cancer: A Co-Clinical Trial With Genoproteomic Discovery [NCT02547987] | Phase 2 | 25 participants (Actual) | Interventional | 2015-11-01 | Active, not recruiting |
| Phase II Trial Of Weekly Irinotecan And Docetaxel In Recurrent Or Metastatic Head And Neck Carcinoma [NCT00040807] | Phase 2 | 0 participants | Interventional | 2002-11-19 | Completed |
| 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 1 | 17 participants (Actual) | Interventional | 2019-07-10 | Completed |
| Open-label Phase I-II Clinical Trial to Evaluate Treatment With Myocet/Taxotere/Herceptin as Primary Chemotherapy Treatment for HER2neu Positive Breast Cancer Patients [NCT00129896] | Phase 1/Phase 2 | 73 participants (Actual) | Interventional | 2004-01-31 | Completed |
| Randomized, Controlled Biomarker Study Evaluating the Anti-angiogenic Activity of Sunitinib in Hormone Refractory Prostate Cancer Patients Treated by Docetaxel [NCT00795171] | Phase 2 | 60 participants (Anticipated) | Interventional | 2008-11-30 | Recruiting |
| A Randomized, Multicenter, Open Phase III Study Comparing a Dose-Intensified 8 Week Schedule of Adriamycin and Docetaxel (ADOC) With a Sequential 24 Week Schedule of Adriamycin/Cyclophosphamide Followed by Docetaxel (AC-DOC) Regimen as Preoperative Therap [NCT00793377] | Phase 3 | 913 participants (Actual) | Interventional | | Completed |
| A Feasibility Phase II Study of Gemcitabine With Docetaxel With Concurrent 3-D Conformal Radiation Plus Continuous Infusion 5-Fluorouracil in the Treatment of Resected Cholangiocarcinoma, Gallbladder, Pancreatic and Ampullary Cancers [NCT00660699] | Phase 2 | 50 participants (Actual) | Interventional | 2002-09-30 | Completed |
| Phase IIB Study of Trimodality Management of Clinical T1bN0M0 Cancers of the Esophagus [NCT01217060] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2010-10-31 | Completed |
| Phase II Single-Arm Trial Comparing the Use of FLT PET to Standard Computed Tomography to Assess the Treatment Response of Neoadjuvant Docetaxel and Cisplatin in Stage IB-IIIA Resectable Non-small Cell Lung Cancer [NCT00963807] | Phase 2 | 26 participants (Actual) | Interventional | 2009-09-30 | Completed |
| A Randomized Parallel Group Phase III Trial of OSE2101 as 2nd or 3rd Line Compared With Standard Treatment (Docetaxel or Pemetrexed) in HLA-A2 Positive Patients With Advanced Non-Small-Cell Lung Cancer With Progressive Disease After Last Treatment With Im [NCT02654587] | Phase 3 | 363 participants (Anticipated) | Interventional | 2016-02-29 | Active, not recruiting |
| A Randomised Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide Compared to Doxorubicin and Cyclophosphamide in Operable Node Negative Breast Cancer With Normal Topoisomerase IIα Expression [NCT00801411] | Phase 2 | 318 participants (Anticipated) | Interventional | 2008-10-31 | Recruiting |
| 0822GCC Randomized, Double-Blind, Placebo-Controlled Multicenter Phase 2 Study of the Efficacy and Safety of Apricoxib in Combination With Either Docetaxel or Pemetrexed in Non-Small Cell Lung Cancer Patients [NCT00771953] | Phase 2 | 109 participants (Actual) | Interventional | 2008-11-30 | Completed |
| A Randomized, Double-Blind, Phase 3 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer Following Disease Progression After One Prior Platinum-Based Therapy [NCT01168973] | Phase 3 | 1,253 participants (Actual) | Interventional | 2010-12-31 | Completed |
| 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 1 | 6 participants (Actual) | Interventional | 2008-10-31 | Terminated(stopped due to Low accrual) |
| Neoadjuvant Therapy With Trastuzumab and Docetaxel Followed by Trastuzumab, Caelyx (Liposomal Doxorubicin) and Cyclophosphamide in Operable or Locally Advanced Her-2 Positive Breast Cancer [NCT00434031] | Phase 2 | 0 participants (Actual) | Interventional | 2007-09-30 | Withdrawn(stopped due to lack of enrollment) |
| Phase 1/1b Study to Evaluate the Safety and Activity of TTX-030 (Anti-CD39) in Combination With Pembrolizumab or Budigalimab and/or Chemotherapy in Subjects With Advanced Solid Tumors [NCT04306900] | Phase 1 | 185 participants (Anticipated) | Interventional | 2020-03-30 | Active, not recruiting |
| Phase Ib Trial of Pembrolizumab (MK-3475) With Platinum-Based Chemotherapy in Small Cell/Neuroendocrine Cancers of Urothelium and Prostate [NCT03582475] | Phase 1 | 15 participants (Actual) | Interventional | 2018-12-20 | Completed |
| A Study to Evaluate Serplulimab in Combination With Docetaxel +S-1 VS. Docetaxel +S-1 as Adjuvant Treatment Therapy in Stage IIIc Gastric Cancer(PD-L1 + / MSI-H / EBV +/dMMR) [NCT05769725] | Phase 2 | 70 participants (Anticipated) | Interventional | 2023-03-01 | Recruiting |
| Utility of Exosomal microRNAs to Predict Response to Androgen Deprivation Therapy in Prostate Cancer Patients [NCT02366494] | | 60 participants (Anticipated) | Observational | 2015-04-29 | Active, not recruiting |
| A Phase I/II Study Evaluating the Combination of Weekly Docetaxel and Cisplatin Together With Capecitabine and Bevacizumab in Patients With Advanced Gastric Cancer [NCT00845884] | Phase 1/Phase 2 | 49 participants (Anticipated) | Interventional | 2009-02-28 | Not yet recruiting |
| An Extension Multicenter Phase II Open Label Non-comparative Trial of RP56976 Administered Every Three Weeks in Combination With Daily Prednisolone for Metastatic Hormone Refractory Prostate Cancer. [NCT00723086] | Phase 2 | 16 participants (Actual) | Interventional | 2005-05-31 | Completed |
| PhaseⅡ Study of Weekly Docetaxel and Fixed-Dose Rate Gemcitabine in Patient With Previously Treated Advanced Soft Tissue and Bone Sarcoma Prospective, Open Label, Multi-Institutional [NCT00807261] | Phase 2 | 30 participants (Anticipated) | Interventional | 2008-09-30 | Enrolling by invitation |
| Phase I/II Study of Preoperative Radiation and Docetaxel Activity in High Risk Localized Prostate Cancer [NCT00321698] | Phase 1/Phase 2 | 25 participants (Actual) | Interventional | 2006-01-31 | Active, not recruiting |
| Phase II Study of Adjusted-dose Docetaxel-oxaliplatin-capecitabine in Patients With Advanced Gastric Adenocarcinoma and Intermediate General Status. [NCT00733616] | Phase 2 | 44 participants (Actual) | Interventional | 2008-11-30 | Completed |
| A Randomized, Double Blind, Placebo-Controlled, Phase IIIb Study of the Efficacy and Safety of Continuing Enzalutamide in Chemotherapy Naïve Metastatic Castration Resistant Prostate Cancer Patients Treated With Docetaxel Plus Prednisolone Who Have Progres [NCT02288247] | Phase 3 | 688 participants (Actual) | Interventional | 2014-12-01 | Active, not recruiting |
| A Randomised Phase II Feasibility Study Investigating the Biological Effects of the Addition of Zoledronic Acid to Neoadjuvant Combination Chemotherapy on Invasive Breast Cancer [NCT00525759] | Phase 2 | 40 participants (Actual) | Interventional | 2007-07-31 | Completed |
| Phase I Study Evaluating Extended Field Intensity Modulated Radiation Therapy and Docetaxel in Patients With Prostate Cancer Associated With Pelvic Node Metastasis [NCT00482807] | Phase 1 | 9 participants (Actual) | Interventional | 2004-08-31 | Completed |
| An Open-Label, Multicenter, Randomized, Phase II Study to Evaluate the Efficacy and Safety of Two Combination Dose Regimens: Capecitabine + Epirubicin + Cyclophosphamide (CEX) Versus 5-FU + Epirubicin + Cyclophosphamide (FEC 100) as Neoadjuvant Therapy in [NCT02846428] | Phase 2 | 182 participants (Actual) | Interventional | 2004-03-31 | Completed |
| Genotype-driven Treatment of Advanced Non-small Cell Lung Cancer Based on mRNA Expression of ERCC1 & RRM1 as First-line Chemotherapy [NCT00736814] | Phase 2 | 117 participants (Anticipated) | Interventional | 2008-06-30 | Recruiting |
| A Phase III Randomised Study Comparing Concomitant Radiochemotherapy With Cisplatin and Docetaxel as Induction Versus Consolidation Treatment in Patients With Locally Advanced Unresectable Non-small Cell Lung Cancer. [NCT00633568] | Phase 3 | 125 participants (Actual) | Interventional | 2007-01-31 | Terminated(stopped due to Slow recruitment) |
| A Study to Evaluate Camrelizumab in Combination With Docetaxel +S-1 Sequenced by Camrelizumab+S-1 as Adjuvant Treatment Therapy in Stage III Gastric Cancer (PD-L1 + / MSI-H / EBV +/dMMR) [NCT04152889] | Phase 2 | 20 participants (Anticipated) | Interventional | 2020-04-14 | Recruiting |
| A Phase I, Open-label, Dose-escalation, Safety, Pharmacokinetic, and Pharmacodynamic Study of Intravenously Administered ATI-1123, a Liposomal Docetaxel Formulation, on an Every 3 Week Schedule, in Patients With Advanced Solid Tumors [NCT01041235] | Phase 1 | 29 participants (Actual) | Interventional | 2009-12-31 | Completed |
| A Single Arm Phase II Feasibility Study of Neoadjuvant Docetaxel, Oxaliplatin and S-1 Chemotherapy in Potentially Operable Gastric or Gastroesophageal Adenocarcinoma. [NCT00816543] | Phase 2 | 41 participants (Actual) | Interventional | 2008-12-31 | Completed |
| A Phase II, Single-center, Dynamic Observational Study With PET of 68Ga-HER2-affibody in Anti-HER2 Treatment [NCT04769050] | | 50 participants (Anticipated) | Observational | 2021-02-18 | Recruiting |
| Phase Ⅱ Study of Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation for Stage Ⅲ Nasopharyngeal Carcinoma [NCT00816855] | Phase 2 | 52 participants (Anticipated) | Interventional | 2007-02-28 | Recruiting |
| A Randomized Phase 2 Study of LY2181308 in Combination With Docetaxel Versus Docetaxel in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Were Previously Treated With First Line Chemotherapy [NCT01107444] | Phase 2 | 180 participants (Actual) | Interventional | 2010-05-31 | Completed |
| Randomized Phase II Study of Docetaxel Followed by Vandetanib (ZD6474) vs. Docetaxel Plus Vandetanib in Patients With Persistent or Recurrent Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Carcinoma [NCT00872989] | Phase 2 | 129 participants (Actual) | Interventional | 2010-03-31 | Completed |
| Phase 2 Study of Comparison Between XELOX (Capecitabine and Oxaliplatin) and Docetaxel, Oxaliplatin and S1 Regimen as Neoadjuvant Chemotherapy for Patients With Locally Advanced Gastric Cancer [NCT02623153] | Phase 2 | 200 participants (Anticipated) | Interventional | 2016-01-31 | Not yet recruiting |
| A Phase I/IIa Study of Safety and Efficacy of Alpharadin® With Docetaxel in Patients With Bone Metastasis From Castration-Resistant Prostate Cancer [NCT01106352] | Phase 1/Phase 2 | 70 participants (Actual) | Interventional | 2010-07-31 | Completed |
| Phase II Trial of Neoadjuvant Docetaxel ± Metronomic Capecitabine/CTX Followed by FEC in Women With Operable Triple Negative Breast Cancer [NCT02897050] | Phase 2 | 170 participants (Anticipated) | Interventional | 2016-09-30 | Suspended |
| A Phase III Clinical Trial Comparing the Combination of TC Plus Bevacizumab to TC Alone and to TAC for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer [NCT00887536] | Phase 3 | 1,613 participants (Actual) | Interventional | 2009-05-31 | Completed |
| Open-Label Study of Bevacizumab (Avastin®) and Taxane Monotherapy for the First-Line Treatment of Patients With Advanced Triple Negative Breast Cancer [NCT01094184] | Phase 4 | 49 participants (Actual) | Interventional | 2010-03-31 | Completed |
| Advanced Non-small Cell Lung Cancer With Chinese Medicine Comprehensive Treatment Plan [NCT02777788] | Phase 2/Phase 3 | 120 participants (Anticipated) | Interventional | 2014-09-30 | Active, not recruiting |
| Randomised Comparison of Adjuvant Docetaxel / Cyclophosphamide With Sequential Adjuvant EC / Docetaxel Chemotherapy in Patients With HER2/Neu Negative Early Breast Cancer [NCT01049425] | Phase 3 | 3,198 participants (Actual) | Interventional | 2009-02-05 | Completed |
| A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer [NCT00567190] | Phase 3 | 808 participants (Actual) | Interventional | 2008-02-12 | Completed |
| 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 2 | 214 participants (Actual) | Interventional | 2006-08-31 | Completed |
| A Phase 1b Study to Assess the Safety Profile, Pharmacokinetics, and Anti-VEGF Activity of PTC299 in Patients With Advanced Cancer [NCT00704821] | Phase 1 | 76 participants (Actual) | Interventional | 2008-07-03 | Terminated |
| Randomized, Single-blind, Multicenter, Parallel Group Clinical Trial to Assess Efficacy and Safety of NNG-TMAB (Trastuzumab) in Combination With Docetaxel on Recurrent or Metastatic Breast Cancer Patients With Positive HER2 [NCT05301010] | Phase 3 | 128 participants (Actual) | Interventional | 2018-02-02 | Completed |
| A Prospective Multicenter Study With 5-FU, Leucovorin, Oxaliplatin and Docetaxel (FLOT) in Patients With Locally Advanced, Limited Metastatic or Extensive Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction [NCT00849615] | Phase 2 | 252 participants (Actual) | Interventional | 2009-02-28 | Completed |
| A Multicenter Phase III Randomized Trial Comparing Docetaxel in Combination With Doxorubicin and Cyclophosphamide (TAC) Versus 5-fluorouracil in Combination With Doxorubicin and Cyclophosphamide (FAC) as Adjuvant Treatment of Operable Breast Cancer Patien [NCT00688740] | Phase 3 | 1,491 participants (Actual) | Interventional | 1997-06-30 | Completed |
| A Phase 1 Study to Assess Mass Balance, Pharmacokinetics, and Metabolism of [14C]-Pevonedistat in Patients With Advanced Solid Tumors [NCT03057366] | Phase 1 | 8 participants (Actual) | Interventional | 2017-05-11 | Completed |
| A Phase II Study of Gemzar, Taxotere, and Xeloda (GTX) for Adjuvant Pancreatic Cancer [NCT00882310] | Phase 2 | 37 participants (Actual) | Interventional | 2006-09-30 | Completed |
| A Randomized, 3 Arm, Multicenter, Phase III Study to Evaluate the Efficacy and the Safety of T-DM1 Combined With Pertuzumab or T-DM1 Combined With Pertuzumab-Placebo (Blinded for Pertuzumab), Versus the Combination of Trastuzumab Plus Taxane, as First Lin [NCT01120184] | Phase 3 | 1,095 participants (Actual) | Interventional | 2010-07-31 | Completed |
| A Phase I, Dose-Escalation Study of the Safety, Tolerability, and Pharmacokinetics of Intravenous Aflibercept in Combination With Intravenous Docetaxel Administered Every 3 Weeks in Patients With Advanced Solid Malignancies [NCT00545246] | Phase 1 | 12 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Study of KN026 in Combination With Docetaxel as Neoadjuvant Therapy in Patients With Early-stage or Locally Advanced HER2-positive Breast Cancer [NCT04881929] | Phase 2 | 30 participants (Anticipated) | Interventional | 2021-08-09 | Recruiting |
| A Randomised Phase II Feasibility Study of Docetaxel (Taxotere®) Plus Prednisolone vs. Docetaxel (Taxotere®) Plus Prednisolone Plus Zoledronic Acid (Zometa®) vs. Docetaxel (Taxotere®) Plus Prednisolone Plus Strontium-89 vs. Docetaxel (Taxotere®) Plus Pred [NCT00554918] | Phase 2 | 300 participants (Anticipated) | Interventional | 2005-02-28 | Completed |
| Induction Chemotherapy Followed by Chemoradiation With Cetuximab and Cisplatin for Inoperable Squamous Cell Carcinoma of the Head and Neck [NCT00868491] | Phase 2 | 30 participants (Anticipated) | Interventional | 2008-03-31 | Completed |
| A Randomized, Multicenter, Double-Blind, Parallel-Controlled, Phase III Clinical Study to Evaluate QL1209/Pertuzumab in Combination With Docetaxel in Patients With Early-Stage or Locally Advanced HER2-Positive and ER/PR-negative Breast Cancer. [NCT04629846] | Phase 3 | 544 participants (Anticipated) | Interventional | 2020-11-30 | Not yet recruiting |
| Phase II Study of SPI-1620 in Combination With Docetaxel as a Second-Line Treatment for Patients With Advanced Biliary Cancer [NCT01773785] | Phase 2 | 30 participants (Actual) | Interventional | 2013-04-30 | Terminated(stopped due to The study completed the first phase and did not meet efficacy end point to enter into the randomized phase.) |
| Phase III Study Comparing the Efficacy of Paclitaxel-bevacizumab With Docetaxel in 2nd or 3rd Line of Treatment of Non Squamous Non Small Cells Lung Cancer [NCT01763671] | Phase 3 | 166 participants (Actual) | Interventional | 2013-05-31 | Completed |
| Phase I Study of Docetaxel, Prednisone and Pazopanib in Men With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) and Poor-Risk Factors [NCT01385228] | Phase 1 | 36 participants (Actual) | Interventional | 2011-06-30 | Completed |
| Analysis of Clinical Outcome, Predictive and Prognostic Factors of Therapeutic Responses in Patients Who Treated With Doxorubicin & Docetaxel Neoadjuvant Chemotherapy in Clinical Stage II or III Breast Cancer [NCT01396655] | Phase 2 | 78 participants (Actual) | Interventional | 2006-07-31 | Completed |
| IXTEND: A Randomized Phase 2 Study to Evaluate the Combination of Ixabepilone Plus Capecitabine or Capecitabine Plus Docetaxel in the Treatment of Metastatic Breast Cancer [NCT00546364] | Phase 2 | 62 participants (Actual) | Interventional | 2008-02-29 | Terminated(stopped due to Slow Accrual) |
| A Phase Ib/II Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of HMPL-453 (FGFR Inhibitor) Combined With Chemotherapy or Anti-PD-1 Antibody in Patients With Advanced Solid Tumors [NCT05173142] | Phase 1/Phase 2 | 141 participants (Anticipated) | Interventional | 2022-01-22 | Recruiting |
| PreOperative Treatment With chEmotheRapy or chemoRAdiatioN in esophaGeal or gastroEsophageal adenocaRcinoma [NCT01404156] | Phase 2/Phase 3 | 60 participants (Anticipated) | Interventional | 2015-09-30 | Recruiting |
| A Phase II Trial of Androgen Deprivation, Docetaxel and Enzalutamide in Patients With Metastatic Hormone Sensitive Prostate Cancer [NCT03246347] | Phase 2 | 40 participants (Actual) | Interventional | 2017-08-23 | Active, not recruiting |
| Concomitant Chemotherapy AND Bcl-xL Inhibitor (AT-101) For Bio-selection For Organ Preservation In Patients With Advanced Laryngeal Cancer [NCT01633541] | Phase 2 | 55 participants (Actual) | Interventional | 2012-03-31 | Completed |
| A Phase 1b/2 Study of Tergenpumatucel-L (HyperAcute Lung) Immunotherapy in Combination With the IDO Pathway Inhibitor Indoximod and Docetaxel in Patients With Advanced Previously Treated Non-Small Cell Lung Cancer (NSCLS) [NCT02460367] | Phase 1 | 16 participants (Actual) | Interventional | 2016-01-31 | Terminated(stopped due to Lack of enrollment and changing landscape of standard of care.) |
| PEXG (Cisplatin, Epirubicin, Capecitabine, Gemcitabine) Versus PDXG (Cisplatin, Docetaxel, Capecitabine, Gemcitabine) in Locally Advanced or Metastatic Pancreatic Adenocarcinoma: A Randomized Phase II Trial [NCT00966706] | Phase 2 | 105 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Non-Metastatic High-Risk Prostate Cancer Patients With Biochemical Relapse Only After Local Treatment. A Prospective Randomized Phase III Study Comparing Hormonal Therapy +/-Docetaxel [NCT00764166] | Phase 3 | 254 participants (Actual) | Interventional | 2003-06-30 | Active, not recruiting |
| Phase 2 Study of Gemcitabine and Docetaxel Combination Chemotherapy in Patients With Carcinoma of Unknown Primary [NCT02590055] | Phase 2 | 29 participants (Anticipated) | Interventional | 2015-10-31 | Recruiting |
| Multicenter, Open Lable Phase II Study to Evaluate the Safety and Efficacy of a Perioperative Chemotherapy With Docetaxel, Cisplatin and Capecitabine in Patients With Gastric Adenocarcinoma, Adenocarcinoma of the Gastro-esophageal Junction or the Distal E [NCT00865982] | Phase 2 | 50 participants (Anticipated) | Interventional | 2008-09-30 | Active, not recruiting |
| Docetaxel and Irinotecan Combination as a Second Line Treatment of Metastatic Gastric Cancer; a Phase II Multicenter Study [NCT04770623] | Phase 2 | 24 participants (Actual) | Interventional | 2021-03-05 | Completed |
| Double-blind, Randomized, Multicenter, Phase III Clinical Study to Compare the Efficacy and to Evaluate the Safety and Immunogenicity of Trastuzumab Biosimilar HLX02 and EU-sourced Herceptin® in Previously Untreated HER2 Overexpressing Metastatic Breast C [NCT03084237] | Phase 3 | 649 participants (Actual) | Interventional | 2016-11-30 | Completed |
| Neoadjuvant Hormonal Ablation, Imatinib Mesylate and Docetaxel Followed by Radical Prostatectomy for High-Risk Localized Prostate Cancer [NCT00500110] | Phase 2 | 39 participants (Actual) | Interventional | 2003-06-30 | Completed |
| A Multinational, Randomized, Double-Blind Study Comparing Aflibercept Versus Placebo in Patients Treated With Second-Line Docetaxel After Failure of One Platinum Based Therapy for Locally Advanced or Metastatic Non-Small-Cell Lung Cancer [NCT00532155] | Phase 3 | 913 participants (Actual) | Interventional | 2007-09-30 | Completed |
| Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taipei, Taiwan [NCT01004601] | | 179 participants (Actual) | Interventional | 2005-03-31 | Completed |
| A Phase Ila Exploratory 2-stage Design Study of CPC634 (CriPec® Docetaxel) Monotherapy in Subjects With Platinum Resistant Ovarian Cancer. [NCT03742713] | Phase 2 | 25 participants (Actual) | Interventional | 2018-10-01 | Completed |
| An Open-Label, Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent Metastatic Nasopharyngeal Carcinoma [NCT05126719] | Phase 2 | 238 participants (Anticipated) | Interventional | 2021-08-04 | Recruiting |
| KN035, a Single Domain PD-L1 Subcutanuous Injection Antibody, in Combination With Trastuzumab and Docetaxel in HER2-positive Breast Cancer [NCT04034823] | Phase 2 | 59 participants (Anticipated) | Interventional | 2019-09-01 | Not yet recruiting |
| A Randomised, Double Blind, Placebo Controlled, Multicentre Study to Evaluate the Efficacy and Safety of Bevacizumab in Combination With Docetaxel in Comparison With Docetaxel Plus Placebo, as First Line Treatment for Patients With HER2 Negative Metastati [NCT00333775] | Phase 3 | 736 participants (Actual) | Interventional | 2006-03-31 | Completed |
| 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 2 | 18 participants (Actual) | Interventional | 2009-04-30 | Completed |
| A Phase 1 Study of MLN8237, an Aurora A Kinase Inhibitor, in Patients With Advanced Solid Tumors Including Castration-Resistant Prostate Cancer Receiving a Standard Docetaxel Regimen [NCT01094288] | Phase 1 | 41 participants (Actual) | Interventional | 2010-08-17 | Completed |
| 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 4 | 110 participants (Anticipated) | Interventional | 2021-07-19 | Recruiting |
| A Randomized Phase III Trial of Adjuvant Chemotherapy in Patients With Early Stage Non-Small Cell Lung Cancer Associated With Banking of Frozen Tumor Specimens and Collection of Gene Expression Profile Data [NCT00863512] | Phase 3 | 34 participants (Actual) | Interventional | 2009-03-31 | Terminated |
| A Multicenter, Phase II Trial of the Safety and Efficacy of Amplimexon® (Imexon for Injection) in Combination With Taxotere® (Docetaxel) for Previously Treated Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) [NCT00697060] | Phase 2 | 0 participants (Actual) | Interventional | 2010-08-31 | Withdrawn(stopped due to Study cancelled prior to start due to change in company priorities.) |
| 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 1 | 98 participants (Anticipated) | Interventional | 2015-12-31 | Completed |
| A Phase I/II Trial of Post-Prostatectomy Radiation Therapy, Hormonal Therapy and Concurrent Docetaxel for High Risk Pathologic T2-T3NO (Tumor-3, Node-0) Prostate Cancer [NCT00669162] | Phase 1/Phase 2 | 27 participants (Actual) | Interventional | 2012-08-31 | Completed |
| Target Dosing of Docetaxel Through Pharmacokinetic/Pharmacodynamic Optimisation of the First Chemotherapeutic Cycle [NCT00703378] | Phase 1/Phase 2 | 33 participants (Actual) | Interventional | 2006-05-31 | Completed |
| A Randomized, Phase II Study Comparing DA (Paclitaxel, Pirarubicin) With DAC ( Paclitaxel, Pirarubicin，Cyclophosphamide) as Postoperative Adjuvant Treatment for Early-stage Breast Cancer [NCT02838225] | Phase 2 | 300 participants (Actual) | Interventional | 2009-01-31 | Completed |
| Phase 1 Trial Evaluating the Safety and Tolerability of NanoDoce® Intratumoral Injection in Subjects With Localized Renal Cell Carcinoma [NCT04260360] | Phase 1 | 0 participants (Actual) | Interventional | 2020-04-30 | Withdrawn(stopped due to Not initiated) |
| Induction Chemotherapy With Nedaplatin, Docetaxel and 5-Fluorouracil Followed by Concurrent Nedaplatin and Radiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: a Single Arm, Open Label, Multicenter, Phase II Clinical Study. [NCT04834206] | Phase 2 | 32 participants (Actual) | Interventional | 2021-05-01 | Completed |
| Phase III Study of Chemo-hormonal Therapy Versus Hormonal Therapy Alone in Advanced Hormone-naives Prostate Cancer Patients. [NCT00796458] | Phase 3 | 200 participants (Anticipated) | Interventional | 2005-04-30 | Recruiting |
| A Phase II Study of Weekly Docetaxel and Capecitabine for Persistent or Recurrent Platinum Resistant Epithelial Carcinoma of the Ovary, Fallopian Tube or Peritoneum [NCT00354601] | Phase 2 | 2 participants (Actual) | Interventional | 2006-01-31 | Terminated(stopped due to funding withdrawn) |
| ACADEMIC: A Randomized Phase II Clinical Trial of ADT Combined With Abiraterone or Docetaxel in Metastatic Hormone Sensitive Prostate Cancer [NCT03827473] | Phase 2 | 1 participants (Actual) | Interventional | 2019-02-08 | Terminated(stopped due to The trial was closed because the changing standard of care landscape, making this trial not impactful anymore.) |
| A Phase I, Multi-arm, Dose Escalation Study of Brivanib Alaninate Combined With Several Chemotherapy Regimens in Subjects With Solid Tumors [NCT00798252] | Phase 1 | 111 participants (Actual) | Interventional | 2009-03-31 | Completed |
| Docetaxel (DTX) - Ifosfamide (IFX) As First Line Chemotherapy In Metastatic Breast Cancer [NCT00026078] | Phase 2 | 42 participants (Anticipated) | Interventional | 2001-03-31 | Recruiting |
| ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers [NCT05616624] | Phase 1/Phase 2 | 108 participants (Anticipated) | Interventional | 2023-04-05 | Recruiting |
| Multimodality Management of Head and Neck Cancer: A Phase II Trial of Induction Chemotherapy, Organ Preservation Surgery, and Concurrent Chemoradiotherapy [NCT00544414] | Phase 2 | 31 participants (Actual) | Interventional | 2000-06-07 | Active, not recruiting |
| Docetaxel Followed by Provenge in Castration-Resistant Prostate Cancer [NCT02793765] | Phase 2 | 0 participants (Actual) | Interventional | 2016-12-31 | Withdrawn(stopped due to Dendreon was sold and new company decided not to fund study.) |
| Provenge Followed by Docetaxel in Castration-Resistant Prostate Cancer [NCT02793219] | Phase 2 | 0 participants (Actual) | Interventional | 2016-12-31 | Withdrawn(stopped due to Dendreon was sold and new company decided not to fund study.) |
| Randomized Phase II Trial, Comparing Standard of Care Chemotherapy (Pemetrexed or Docetaxel) Plus Erlotinib to Standard of Care Chemotherapy (Pemetrexed or Docetaxel) Alone in EGFR TKI-Responsive Non-Small Cell Lung Cancer [NCT00660816] | Phase 2 | 46 participants (Actual) | Interventional | 2008-01-31 | Completed |
| Open-label, Multicenter,PhaseI Trial in Order To Determine the Safety and Pharmacokinetics of BAY43-9006 in Combination With Docetaxel as First-line Treatment in Metastatic Hormone Refractory Prostate Cancer Patients [NCT00405210] | Phase 1 | 38 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Absorption and Excretion of Docetaxel (as ModraDoc 006 Tablets) After Oral Administration in Combination With Ritonavir [NCT05242926] | Phase 1 | 0 participants (Actual) | Interventional | 2017-10-31 | Withdrawn(stopped due to Pending further development) |
| Postoperative Concurrent Chemoradiotherapy With Docetaxel for High-Risk Squamous Cell Carcinoma of Head and Neck，A Non-Randomized Phase II Trial [NCT02776137] | Phase 2 | 91 participants (Actual) | Interventional | 2016-03-31 | Completed |
| Concurrent Docetaxel Plus Cisplatin or Cisplatin Alone With Intensity-modulated Radiotherapy in High Risk Locregionally Advanced Nasopharyngeal Carcinoma: a Phase 2 Randomized Controlled Trial [NCT02610556] | Phase 2 | 130 participants (Anticipated) | Interventional | 2016-01-31 | 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 2 | 34 participants (Actual) | Interventional | 2005-10-31 | Terminated(stopped due to Poor accrual) |
| Randomized, Controlled, Multicenter Phase III Clinical Study Evaluating the Efficacy and Safety of RC48-ADC for the Treatment of Locally Advanced or Metastatic Breast Cancer With Low Expression of HER2 [NCT04400695] | Phase 3 | 366 participants (Anticipated) | Interventional | 2020-09-29 | Recruiting |
| A Randomized Phase II Study of PEP02, Irinotecan or Docetaxel as a Second Line Therapy in Patients With Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma [NCT00813072] | Phase 2 | 135 participants (Actual) | Interventional | 2007-11-30 | Completed |
| An Open Label Study to Assess the Effect of First-line Treatment With Avastin in Combination With Docetaxel and Cisplatin on Progression-free Survival in Patients With Metastatic or Locally Advanced Non-small Cell Lung Cancer [NCT00661778] | Phase 2 | 50 participants (Actual) | Interventional | 2007-07-31 | Completed |
| A Randomized Phase 2 Study of LY2181308 in Combination With Docetaxel Versus Docetaxel in Hormone Refractory Prostate Cancer [NCT00642018] | Phase 2 | 154 participants (Actual) | Interventional | 2008-03-31 | Completed |
| Induction Chemotherapy Followed by Cetuximab Plus Definitive Radiotherapy Versus Radiation Plus Cisplatin [NCT00999700] | Phase 3 | 282 participants (Anticipated) | Interventional | 2009-09-30 | Active, not recruiting |
| Secondary Adjuvant (Rescue) Treatment With Docetaxel (Taxotere) and Detection of Isolated Tumor Cells in Bone Marrow as a Surrogate Marker for Effect in Node Positive and High Risk Node Negative Breast Cancer After Standard Adjuvant Epirubicin-containing [NCT00248703] | Phase 2 | 1,128 participants (Actual) | Interventional | 2003-10-31 | Completed |
| Phase I Study of Induction Cisplatin, Docetaxel, and Nintedanib for Stage IB-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection [NCT02225405] | Phase 1 | 26 participants (Actual) | Interventional | 2015-04-03 | Active, not recruiting |
| A Phase II Study of Sorafenib in Combination With Docetaxel in Patients With Androgen-Independent Prostate Cancer [NCT00589420] | Phase 2 | 18 participants (Actual) | Interventional | 2007-07-27 | Completed |
| Phase ⅡStudy of Neoadjuvant Chemotherapy Followed by Concurrent Chemoradiation for Stage ⅣAB Nasopharyngeal Carcinoma [NCT00816816] | Phase 2 | 64 participants (Anticipated) | Interventional | 2007-02-28 | Recruiting |
| A Pilot Study of Adjuvant Docetaxel Plus Gemcitabine in Patients With Completely Resected Leiomyosarcoma (LMS) of the Uterus [NCT00614835] | | 25 participants (Actual) | Interventional | 2001-08-31 | Completed |
| 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 2 | 140 participants (Actual) | Interventional | 2001-10-31 | Completed |
| PD-1 Immune Checkpoint Inhibitors and Immune-Related Adverse Events: a Cohort Study [NCT04115410] | | 4,724 participants (Anticipated) | Observational | 2020-07-01 | Not yet recruiting |
| A Multicenter Phase II Trial of Docetaxel Combined With Cisplatin (CDDP) as a Neo-Adjuvant Chemotherapy in Patients With Loco Regionally Advanced Undifferentiated Carcinoma of Nasopharyngeal Type (UCNT) [NCT00916097] | Phase 2 | 66 participants (Actual) | Interventional | 2002-07-31 | Completed |
| Phase II Study of SGN-15 (cBR96 - Doxorubicin Immunoconjugate) Combined With Taxotere in Patients With Hormone Refractory Prostate Carcinoma [NCT00031187] | Phase 2 | 160 participants | Interventional | 2000-10-31 | Completed |
| Pharmacokinetics of Weekly Docetaxel in Patients Age 65 and Older With Metastatic Breast or Lung Cancer [NCT00059943] | Phase 2 | 0 participants | Interventional | 2002-09-30 | Completed |
| A Pilot Study of Molecularly Tailored Therapy for Patients With Metastatic Pancreatic Cancer [NCT01888978] | Phase 2 | 19 participants (Actual) | Interventional | 2012-12-31 | Completed |
| Ph 2 Trial of G-FLIP (Low Doses Gemcitabine, 5FU, Leucovorin, Irinotecan & Oxaliplatin), Followed by G-FLIP-DM (G-FLIP + Low Doses Docetaxel & MitomycinC), When Used in Combination With Vitamin C, in Patients With Advanced Pancreatic Cancer [NCT01905150] | Phase 2 | 34 participants (Actual) | Interventional | 2014-07-31 | Completed |
| Exploratory Evaluation Of A Sequential Administration Of Docetaxel And SU011248 In Women With Advanced Breast Cancer [NCT00291577] | Phase 1 | 22 participants (Actual) | Interventional | 2006-07-31 | Completed |
| A Randomized Phase III Study of Metronomic vs. Intermittent Capecitabine Maintenance Therapy Following First-line Capecitabine and Docetaxel Therapy in HER2-negative Metastatic Breast Cancer [NCT01917279] | Phase 3 | 280 participants (Anticipated) | Interventional | 2013-10-31 | Recruiting |
| 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 3 | 4 participants (Anticipated) | Interventional | 2008-08-31 | Recruiting |
| A 2-Part Phase 2 Study of SPI-1620 in Combination With Docetaxel Versus Docetaxel Alone for Patients With Non Small-cell Lung Cancer After Failure of First-line Platinum-based Chemotherapy [NCT01741155] | Phase 2 | 34 participants (Actual) | Interventional | 2013-05-31 | Terminated(stopped due to The study did not meet efficacy end point and did not enroll patients in the randomized phase.) |
| Pilot Study of Perioperative Docetaxel, Oxaliplatin, and 5-Fluorouracil (FLOT) in Patients With Gastric or Gastroesophageal Junction Adenocarcinoma [NCT01932580] | Phase 2 | 10 participants (Actual) | Interventional | 2013-08-31 | Completed |
| Phase II Study of Docetaxel and Cisplatin Chemotherapy Versus Docetaxel and Cisplatin Chemotherapy Combined With High Dose Proton Pump Inhibitor in Metastatic Breast Cancer [NCT01069081] | Phase 2 | 94 participants (Actual) | Interventional | 2009-08-31 | Completed |
| A Phase I Study of Docetaxel Plus Synthetic Lycopene in Metastatic Prostate Cancer Patients With Biochemical or Clinical Relapse [NCT01949519] | Phase 1 | 24 participants (Actual) | Interventional | 2013-11-30 | Completed |
| Role of Early 18F-FDG-PET/CT Scan in Predicting Mediastinal Downstaging With Neoadjuvant Chemotherapy in Resectable Stage III A NSCLC [NCT02607423] | Phase 2 | 0 participants (Actual) | Interventional | 2015-11-19 | Withdrawn(stopped due to The study failed to meet its accrual targets.) |
| SUNRISE: A Phase III, Randomized, Double-Blind, Placebo-Controlled Multicenter Trial of Bavituximab Plus Docetaxel Versus Docetaxel Alone in Patients With Previously Treated Stage IIIb/IV Non-Squamous Non Small-Cell Lung Cancer [NCT01999673] | Phase 3 | 582 participants (Anticipated) | Interventional | 2013-12-31 | Completed |
| Clinical Study on Docetaxel Plus Cisplatin(TP) Regimen Combined With Postoperative Radiotherapy for Stage Ia2- IIb Cervical Cancer [NCT01999933] | Phase 2/Phase 3 | 600 participants (Anticipated) | Interventional | 2013-11-30 | Recruiting |
| A Neoadjuvant Study of Chemotherapy Versus Endocrine Therapy in Postmenopausal Patients With Primary Breast Cancer [NCT00963729] | Phase 3 | 756 participants (Anticipated) | Interventional | 2008-09-30 | Completed |
| A Study of Patient Preference Between Cabazitaxel and Docetaxel in First-line Chemotherapy for Metastatic Castrate-resistant Prostate Cancer [NCT02044354] | Phase 3 | 195 participants (Actual) | Interventional | 2014-05-22 | Active, not recruiting |
| A Phase III Trial of Cisplatin/Etoposide/Radiotherapy With or Without Consolidation Docetaxel in Patients With Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer (NSCLC): Hoosier Oncology Group LUN01-24 [NCT00216125] | Phase 3 | 243 participants (Actual) | Interventional | 2002-02-28 | Completed |
| Assessing Tumor Response and IMRT Treatment Planning After Induction Chemotherapy Based on FDG-PET/CT for Locally Advanced Head and Neck Squamous Cell Carcinoma. [NCT02047201] | Phase 2 | 40 participants (Actual) | Interventional | 2013-06-30 | Completed |
| Taxotere and Cisplatin as Induction Chemotherapy in Patients With Stage IIIa N2 Non Small Cell Lung Cancer (NSCLC) [NCT00005868] | Phase 2 | 47 participants (Actual) | Interventional | 2000-03-31 | Completed |
| Phase II Randomized Study of Two Different Schedules of Docetaxel or Paclitaxel for Metastatic Breast Cancer [NCT00006120] | Phase 2 | 0 participants | Interventional | 2000-05-31 | Active, not recruiting |
| Adjuvant AC Followed by Albumin-bound Paclitaxel Versus AC Followed by Taxanes in Breast Cancer: a Prospective, Multi-center, Real-world Study [NCT05287308] | | 500 participants (Anticipated) | Interventional | 2022-03-31 | Not yet recruiting |
| An Open-Label Phase II Study of Navelbine (Vinorelbine Tartrate) and Taxotere (Docetaxel) as First-Line Therapy for Metastatic Breast Cancer [NCT00006682] | Phase 2 | 0 participants | Interventional | 2000-02-29 | Completed |
| Phase I Study Of Gemcitabine, Docetaxel And Carboplatin, With And Without Filrastim Support, Combination Chemotherapy In Patients With Advanced Non-Hematological Malignancies [NCT00008125] | Phase 1 | 25 participants (Actual) | Interventional | 1998-03-31 | Completed |
| A Phase Ib, Open-Label, Multicenter Study Evaluating The Safety, Efficacy and Pharmacokinetics Of Ipatasertib In Combination With Atezolizumab And Docetaxel In Metastatic Castration-Resistant Prostate Cancer. [NCT04404140] | Phase 1 | 6 participants (Actual) | Interventional | 2020-07-09 | Terminated(stopped due to Despite many risk-minimization strategies, the combination of ipatasertib, atezolizumab and docetaxel was challenging due to multiple study treatment modifications required to manage toxicity, making further enrollment inappropriate.) |
| 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 1 | 0 participants | Interventional | 2006-11-30 | Completed |
| Single Arm Study of the Combination of Biweekly Avastin and Docetaxel as the First Line Treatment for Patients With Metastatic Breast Cancer [NCT00979641] | Phase 2 | 65 participants (Actual) | Interventional | 2009-01-31 | Terminated(stopped due to Participants are no longer being examined. The results are published 2016 Anticancer Research 36: 6431-6438) |
| Phase 2 Study of CP-868,596 + Docetaxel, AG-013736 + Docetaxel, or CP-868,596 + AG-013736 + Docetaxel and of Docetaxel Alone in Patients With Stage IIIb or IV Non-Small Cell Lung Cancer. [NCT00386555] | Phase 2 | 0 participants (Actual) | Interventional | 2007-05-31 | Withdrawn(stopped due to Study was cancelled before patient enrollment) |
| Neoadjuvant Treatment of TEC Versus TEC Plus Metformin in Breast Cancer：A Prospective, Randomized Trial [NCT01929811] | Phase 2 | 92 participants (Actual) | Interventional | 2013-10-31 | Terminated(stopped due to Slow enrollment.) |
| A Randomized Phase II Study Of Gemcitabine/Cisplatin, Gemcitabine/Docetaxel, Gemcitabine/Irinotecan, Or Fixed Dose Rate Infusion Gemcitabine In Patients With Metastic Pancreatic Cancer [NCT00012220] | Phase 2 | 259 participants (Actual) | Interventional | 2001-01-31 | Completed |
| A Phase II Study of Doxorubicin and Cyclophosphamide With Sequential Docetaxel in Patients With Hormone-Refractory Prostate Cancer [NCT00005960] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Active, not recruiting |
| Phase II Trial of Docetaxel and Carboplatin as First-Line Therapy for Metastatic Breast Cancer [NCT00005963] | Phase 2 | 53 participants (Actual) | Interventional | 2000-11-30 | Completed |
| Phase II Trial Exploring the Feasibility of Adjuvant Carboplatin/Docetaxel in Curatively Resected Stage I-IIIA Non-Small Cell Lung Cancer [NCT00280735] | Phase 2 | 75 participants (Actual) | Interventional | 2004-05-31 | Completed |
| A Phase III, Double-Blind, Randomised, Placebo-Controlled Study to Assess the Efficacy and Safety of Selumetinib (AZD6244; ARRY-142886) (Hyd-Sulfate) in Combination With Docetaxel, in Patients Receiving Second Line Treatment for KRAS Mutation-Positive Loc [NCT01933932] | Phase 3 | 510 participants (Actual) | Interventional | 2013-09-25 | Active, not recruiting |
| First Prospective Intergroup Translational Research Trial Assessing the Potential Predictive Value of p53 Using a Functional Assay in Yeast in Patients With Locally Advanced/Inflammatory or Large Operable Breast Cancer Prospectively Randomised to a Taxane [NCT00017095] | Phase 3 | 1,856 participants (Actual) | Interventional | 2001-03-31 | Completed |
| A Phase II Trial of Neoadjuvant Cisplatin-Fluorouracil-Docetaxel Chemotherapy, Surgery, and Intraperitoneal (IP) Floxuridine (FUdR) Plus Leucovorin in Patients With Locally Advanced Gastric Cancer [NCT00006038] | Phase 2 | 0 participants | Interventional | 2000-02-29 | Completed |
| Neoadjuvant Therapy With Docetaxel and Ketoconazole in Patients With High-Risk Prostate Cancer: A Pilot Study [NCT00870714] | | 20 participants (Anticipated) | Interventional | 2004-09-30 | Active, not recruiting |
| Positron Emission Tomography Imaging of Bone in Patients With Metastatic Prostate Cancer - A Pilot Study Evaluating Treatment Response [NCT00392938] | | 11 participants (Actual) | Observational | 2005-12-31 | Completed |
| Phase II Trial of Consolidation or Salvage Chemotherapy by Using Weekly Docetaxel/Irinotecan After Cisplatin Plus Weekly 24-Hour Infusion of High-dose 5-Fluorouracil/Leucovorin for Non-resectable Gastric Cancers [NCT00166881] | Phase 2 | 29 participants (Actual) | Interventional | 2000-06-30 | Completed |
| A Multicenter, Randomized, Phase II Study of the Combination of Docetaxel (TAXOTERE) and Concomitant Radiotherapy With or Without Cisplatin in Patients With Locally Advanced Head and Neck Cancer [NCT00521521] | Phase 2 | 86 participants (Actual) | Interventional | 2001-07-31 | Completed |
| A Multi-arm, Multi-stage, Randomized Phase II/III Trial of Immunotherapy Strategies in Metastatic Hormone-sensitive Prostate Cancer [NCT03879122] | Phase 2/Phase 3 | 135 participants (Anticipated) | Interventional | 2019-02-11 | Active, not recruiting |
| Safety and Dose Finding Study of Oral MP470, a Multi-targeted Tyrosine Kinase Inhibitor, in Combination With Standard-of-Care Chemotherapy Regimens [NCT00881166] | Phase 1 | 101 participants (Actual) | Interventional | 2007-11-30 | Completed |
| Phase I Study of TTC (Taxotere/Temodar/Cisplatin) in Metastatic Melanoma Patients [NCT00527761] | Phase 1 | 23 participants (Actual) | Interventional | 2004-08-31 | Completed |
| A Phase I/II Trial of ABI-008 (Nab-docetaxel) in Patients With Metastatic Breast Cancer [NCT00531271] | Phase 1/Phase 2 | 85 participants (Anticipated) | Interventional | 2007-11-01 | Terminated |
| Randomized Study Comparing Induction Chemotherapy With Docetaxel, Cisplatin, 5FU Versus Cisplatin, 5 FU in Patients With T3 and T4 Larynx and Hypopharynx Carcinoma [NCT00169182] | Phase 3 | 220 participants (Actual) | Interventional | 2001-12-15 | Completed |
| A Randomized Phase III Study of Trastuzumab (Herceptin) in Combination With Either Vinorelbine (Navelbine), or Taxane-based Chemotherapy in Patients With HER2 Overexpressing Metastatic Breast Cancer [NCT00146549] | Phase 3 | 250 participants | Interventional | 2001-08-31 | Completed |
| Phase II Study of Tailored-Dose Docetaxel in Metastatic Breast Cancer [NCT00148070] | Phase 2 | 45 participants (Actual) | Interventional | 1999-03-31 | Completed |
| Phase 2 Study of Weekly Topotecan With Docetaxel for Recurrent Small Cell Lung Cancer [NCT00315211] | Phase 2 | 7 participants (Actual) | Interventional | 2004-11-30 | Terminated(stopped due to Slow Accrual) |
| A Randomized Phase III Trial of Gemcitabine and Docetaxel Versus Gemcitabine and Paclitaxel in Patients With Metastatic Breast Cancer: A Comparison of Different Schedules [NCT00236899] | Phase 3 | 241 participants (Actual) | Interventional | 2005-09-30 | Completed |
| 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 3 | 306 participants (Anticipated) | Interventional | 2021-02-01 | Recruiting |
| Toripalimab Combined With FLOT Regimen for Perioperative Treatment of PD-L1 Positive Locally Advanced Resectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma (GEJ): a Prospective, Single-center Clinical Study [NCT05466019] | Phase 2 | 30 participants (Anticipated) | Interventional | 2021-05-01 | Recruiting |
| Phase II Study Evaluating Docetaxel and CDDP as Neoadjuvant Chemotherapy Prior to Surgery, Followed by Adjuvant Docetaxel Plus CDDP in Chemonaive Patients With NSCLC Stage III [NCT00172380] | Phase 2 | 41 participants (Actual) | Interventional | 2005-02-28 | Completed |
| A Double Blind , Randomized, Multicenter Study of Second Line Treatment of Endostar（rh Recombined Endostatin）With Single Docetaxel In NSCLC Patients [NCT00813332] | Phase 4 | 300 participants (Anticipated) | Interventional | 2008-10-31 | Recruiting |
| A Phase 1 Study of Weekly Elesclomol Sodium Plus Docetaxel and Concomitant Prednisone in Subjects With Metastatic Castration Refractory Prostate Cancer (m-CRPC) [NCT00808418] | Phase 1 | 34 participants (Actual) | Interventional | 2008-11-30 | Completed |
| 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 1 | 44 participants (Actual) | Interventional | 2000-02-29 | Completed |
| Phase II Organ Preservation Trial Using Cisplatin Concomitant With Radiation Therapy in Advanced Laryngeal Cancer Patients Who Have Responded to Induction Chemotherapy With Taxotere, Cisplatin, and 5-Fluorouracil (TPF) [NCT01073683] | Phase 2 | 100 participants (Anticipated) | Interventional | 2010-04-30 | Not yet recruiting |
| Postoperative Radiation and Concurrent Chemotherapy With Weekly Docetaxel Versus Cisplatin in Patients With High-risk Oral Cavity Cancer: a Randomized Phase II Clinical Trial [NCT02923258] | Phase 2/Phase 3 | 224 participants (Actual) | Interventional | 2018-04-21 | Completed |
| A Phase II Study Induction Chemotherapy, Neoadjuvant Chemoradiotherapy, Surgical Resection and Adjuvant Chemotherapy for Patients With Locally Advanced, Resectable Pancreatic Adenocarcinoma [NCT00609336] | Phase 2 | 35 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Phase 1 Safety and Pharmacokinetic Study of ABT-263 in Combination With Taxotere® (Docetaxel) in the Treatment of Subjects With Solid Tumors [NCT00888108] | Phase 1 | 41 participants (Actual) | Interventional | 2009-07-31 | Completed |
| A Phase I Investigation of MK-5108 and MK-5108 With Docetaxel in Patients With Advanced Solid Tumors [NCT00543387] | Phase 1 | 35 participants (Actual) | Interventional | 2008-03-27 | Completed |
| A Phase I/II Trial of Docetaxel and Oxaliplatin in Patients With Advanced Gastric Cancer [NCT00533533] | Phase 1/Phase 2 | 68 participants (Anticipated) | Interventional | 2006-01-31 | Completed |
| Multicenter Phase II Trial of Weekly Taxotere and Irinotecan (CPT-11) in Patients With Advanced Non-small Cell Lung Cancer [NCT00819728] | Phase 2 | 35 participants (Actual) | Interventional | 2000-06-30 | Completed |
| [NCT00538525] | | 10 participants (Actual) | Interventional | 2007-09-30 | Completed |
| An Open-Label, Two-Part Study to Determine the Safety, Tolerability, and Activity of Lonafarnib and Docetaxel [NCT00539968] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2007-06-30 | Terminated |
| A Phase II Pilot Study of Estramustine, Docetaxel, and Carboplatin for Patients With Hormone Refractory Prostate Cancer Progressing After Mitoxantrone-Based Chemotherapy. [NCT00183924] | Phase 2 | 20 participants (Actual) | Interventional | 2001-03-31 | Completed |
| Randomized Controlled Trial Comparing Docetaxel-cisplatin Combination With Docetaxel Alone in Elderly Patients With Advanced Non-small-cell Lung Cancer(JCOG0207) [NCT00190476] | Phase 3 | 230 participants | Interventional | 2003-04-30 | Terminated |
| A Randomized, Double-Blind, Two-Way Crossover, Bioequivalence Study of SID530 and Taxotere® in Study Participants With Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Platinum Therapy Failure or Study Participants With Locally Advanced or [NCT00931008] | Phase 3 | 42 participants (Actual) | Interventional | 2009-10-31 | Completed |
| A Nonrandomized Phase II Study: Feasibility and Outcome of Neo Adjuvant Chemotherapy With Oxaliplatin, Fluorodeoxyuridine (FUdR), Taxotere and Leucovorin in the Treatment of Previously Untreated Advanced Esophago-Gastric Carcinoma [NCT00448760] | Phase 2 | 29 participants (Actual) | Interventional | 2004-10-31 | Completed |
| Phase II Trial of Combination Weekly Bortezomib (VELCADE) and Docetaxel (TAXOTERE) in Patients With Recurrent and/ or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) [NCT00425750] | Phase 2 | 25 participants (Actual) | Interventional | 2005-08-31 | Completed |
| A Salvage Trial of AR Inhibition With ADT and Apalutamide With Radiation Therapy Followed by Docetaxel in Men With PSA Recurrent Prostate Cancer After Radical Prostatectomy (STARTAR) [NCT03311555] | Phase 2 | 40 participants (Actual) | Interventional | 2018-03-28 | Completed |
| A Randomized Phase III Trial of Neoadjuvant Therapy in Patients With Palpable and Operable Breast Cancer Evaluating the Effect on Pathologic Complete Response (pCR) of Adding Capecitabine or Gemcitabine to Docetaxel When Administered Before AC With or Wit [NCT00408408] | Phase 3 | 1,206 participants (Actual) | Interventional | 2006-11-30 | Active, not recruiting |
| Randomized Phase II Trial of Sequential Docetaxel Followed by Capecitabine Versus Concomitant, Dose-Dense Docetaxel/Capecitabine as in Induction Therapy for Early Stage Breast Cancer [NCT00209092] | Phase 2 | 51 participants (Actual) | Interventional | 2006-08-31 | Completed |
| A Phase 1 Safety And Pharmacokinetic Study Of SU011248 In Combination With Docetaxel In Patients With Advanced Solid Tumors [NCT00712504] | Phase 1 | 49 participants (Actual) | Interventional | 2004-07-31 | Completed |
| A Randomized, Open-label Study to Compare the Effect of First-line Treatment With Avastin in Combination With Herceptin/Docetaxel and Herceptin/Docetaxel Alone on Progression-free Survival in Patients With HER2 Positive Locally Recurrent or Metastatic Bre [NCT00391092] | Phase 3 | 424 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Adjuvant Treatment of High Risk Uterine Leiomyosarcoma With Gemcitabine/Docetaxel Followed by Doxorubicin: A Phase II Trial [NCT00282087] | Phase 2 | 47 participants (Actual) | Interventional | 2006-01-31 | Completed |
| A Randomized Multicenter Trial of Neoadjuvant Taxotere (T) and Adriamycin/Cytoxan (Ac): A Validation [NCT00206518] | Phase 2 | 167 participants (Actual) | Interventional | 2004-09-30 | Completed |
| Phase II Neoadjuvant Chemotherapy Trial in Clinical Stage II/III Her2Neu Positive Breast Cancer With Sequential AC -> Docetaxel With Concurrent Dual EGFR Kinase Blockade by GW572016 (Lapatinib) Followed by 1 Year Adjuvant Trastuzumab [NCT00404066] | Phase 2 | 21 participants (Actual) | Interventional | 2006-10-31 | Completed |
| A Phase II Evaluation of Docetaxel and Vinorelbine Plus Sargramostim in Patients With Metastatic Malignant Melanoma [NCT00256282] | Phase 2 | 52 participants (Actual) | Interventional | 2003-04-30 | Completed |
| A Phase II Trial of Docetaxel Plus ASA404 as Second-Line Therapy in Patients With Advanced Urothelial Carcinoma: Hoosier Oncology Group GU09-144 [NCT01071928] | Phase 2 | 0 participants (Actual) | Interventional | 2010-06-30 | Withdrawn(stopped due to Lack of efficacy of experimental treatment) |
| A Phase II Study to Assess the Feasibility and Activity of Concomitant Radiation and Docetaxel Chemotherapy Followed by Docetaxel Chemotherapy in Prostate Cancer Patients With a Persistent or Rising PSA After Radical Prostatectomy [NCT00348816] | Phase 2 | 21 participants (Actual) | Interventional | 2006-05-31 | Terminated(stopped due to Loss of funding) |
| A Multi-Center, Randomized Study of Docetaxel, Anthracycline and Cyclophosphamide (TAC) Versus Docetaxel and Cyclophosphamide (TC) in Neoadjuvant Treatment of Triple-Negative or Her2 Positive Breast Cancer [NCT00912444] | Phase 3 | 102 participants (Actual) | Interventional | 2009-07-31 | Terminated(stopped due to TAC treatment was associated with better survial outcome compared with TC treatment, we terminated recruiting and waiting for longer follow up period.) |
| INST 0601C: A Non-Randomized Phase II Protocol of Erlotinib for Patients With Newly Diagnosed, Advanced Non-Small Cell Carcinoma of the Lung [NCT00391586] | Phase 2 | 45 participants (Actual) | Interventional | 2006-07-31 | Terminated(stopped due to PI left institution.) |
| Phase 3 Study of Pemetrexed Versus Docetaxel in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Who Have Had Prior Chemotherapy [NCT00391274] | Phase 3 | 211 participants (Actual) | Interventional | 2006-10-31 | Completed |
| A Phase II Study of Docetaxel, Cisplatin, and Fluorouracil (Modified DCF) With Bevacizumab in Patients With Unresectable or Metastatic Gastroesophageal Adenocarcinoma [NCT00390416] | Phase 2 | 48 participants (Actual) | Interventional | 2006-10-31 | Completed |
| A Phase I Trial of Fractionated Docetaxel and Radium 223 in Metastatic Castration-Resistant Prostate Cancer (CRPC) [NCT03737370] | Phase 1 | 25 participants (Anticipated) | Interventional | 2018-01-30 | Recruiting |
| Multicenter Phase II Trial of Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Docetaxel (T) as Neoadjuvant Treatment for Operable Stage II and IIIA Breast Cancer Patients [NCT00129376] | Phase 2 | 63 participants (Actual) | Interventional | 2003-02-28 | Completed |
| SBRT/LDRT in Combination With Camrelizumab and Apatinib in Metastatic Non-small Cell Lung Cancer Patient Previously Treated With PD-1/L1 Inhibitor and Chemotherapy：a Prospective Exploratory Study [NCT04878107] | Phase 2 | 88 participants (Anticipated) | Interventional | 2022-03-15 | Recruiting |
| Phase III Randomized Trial of Preoperative Chemotherapy Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed by Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients With Stage IIIA (N2) Non-Small Cell [NCT00113386] | Phase 3 | 19 participants (Actual) | Interventional | 2005-04-30 | Terminated(stopped due to This study terminated early due to low accrual.) |
| Phase II Study of Neoadjuvant Pegylated Liposomal Doxorubicin and Docetaxel in Locally Advanced Operable Breast Cancer [NCT00524459] | Phase 2 | 6 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to Terminated by sponsor due to lack of funding) |
| Phase III Study of Docetaxel and Atrasentan Versus Docetaxel and Placebo for Patients With Advanced Hormone Refractory Prostate Cancer [NCT00134056] | Phase 3 | 1,038 participants (Actual) | Interventional | 2006-08-31 | Completed |
| Phase II Trial of Docetaxel Plus Oxaliplatin (DOCOX) With or Without Cetuximab in Patients With Metastatic Gastric and/or Gastroesophageal Junction Adenocarcinoma [NCT00517829] | Phase 2 | 150 participants (Actual) | Interventional | 2007-07-31 | Completed |
| Pilot Study of Neoadjuvant Dose Dense Docetaxel With Correlative Molecular Studies in Stage II/III Breast Cancer [NCT00343512] | Phase 2 | 34 participants (Actual) | Interventional | 2004-02-29 | Terminated(stopped due to closed due to competing neoadjuvant studies for a small patient population) |
| 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 3 | 755 participants (Actual) | Interventional | 2004-12-31 | Completed |
| 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 3 | 186 participants (Anticipated) | Interventional | 2022-08-31 | Recruiting |
| A Phase 2, Open-label, Randomized Controlled Trial of BMS-986218 or BMS-986218 Plus Nivolumab in Combination With Docetaxel in Participants With Metastatic Castration-resistant Prostate Cancer [NCT05169684] | Phase 2 | 10 participants (Actual) | Interventional | 2022-02-14 | Completed |
| A Phase III, Open-labelled, Randomised Study of Neoadjuvant Docetaxel+Oxaliplatin+S-1 (DOS) + Surgery + Adjuvant S-1 Versus Surgery + Adjuvant S-1 in Patients With Resectable Advanced Gastric Cancer [NCT01515748] | Phase 3 | 530 participants (Actual) | Interventional | 2011-12-30 | Completed |
| Phase II Trial of Weekly Gemcitabine and Docetaxel Combination Therapy for Relapsed Ovarian or Peritoneal Cancer [NCT00227721] | Phase 2 | 30 participants (Actual) | Interventional | 2004-02-29 | Completed |
| A Phase II Trial of Avastin in Combination With Docetaxel in Patients With Recurrence of Epithelial Carcinoma of the Ovary/Fallopian Tube/Peritoneum Within 12 Months of Platinum Therapy [NCT00504257] | Phase 2 | 45 participants (Actual) | Interventional | 2007-03-31 | Completed |
| A Randomized Multicenter Trial Comparing Weekly Docetaxel and CMF in the Adjuvant Treatment of Women With High-Risk Breast Cancer Who Are > 65 Years Old or Are Not Candidates for Anthracycline-Based Adjuvant Therapy [NCT00193011] | Phase 3 | 150 participants (Anticipated) | Interventional | 2002-03-31 | Completed |
| Phase II Pilot Study of TPF (Docetaxel, Cisplatin, and 5-FU) Induction Chemotherapy Followed by Concurrent Cisplatin and Reduced Dose Radiation in Locally Advanced Head and Neck Cancer [NCT00352118] | Phase 2 | 4 participants (Actual) | Interventional | 2006-03-31 | Terminated(stopped due to Low dose radiation treatment was not appropriate for these patients.) |
| Phase II Trial of Weekly Docetaxel, Vinorelbine, and Herceptin in the First-Line Treatment of Patients With Metastatic Breast Cancer and Overexpression of Her-2 [NCT00193089] | Phase 2 | 60 participants (Actual) | Interventional | 2001-04-30 | Completed |
| An Open-Label, Non-Randomized Phase II Study of Alvocidib (Flavopiridol) in Combination With Docetaxel in Refractory, Metastatic Pancreatic Cancer (NCI #6366) [NCT00331682] | Phase 2 | 10 participants (Actual) | Interventional | 2006-03-31 | Completed |
| 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 2 | 218 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Salvage Radiation Therapy and Docetaxel (Taxotere) for Biochemical Failure After Radical Prostatectomy [NCT00480857] | Phase 2 | 19 participants (Actual) | Interventional | 2007-03-31 | Terminated(stopped due to Lack of funding.) |
| A Phase II, Double-blind, Placebo-controlled, Randomised Study to Assess the Efficacy and Safety of Docetaxel (Taxotere)/Prednisolone/ZD6474 vs Docetaxel/Prednisolone/Placebo in Patients With Hormone Refractory Prostrate Cancer (HRPC) [NCT00498797] | Phase 2 | 86 participants (Actual) | Interventional | 2005-12-31 | Completed |
| A Pilot (Phase I) Study of Weekly Docetaxel and Cetuximab Chemoradiation for Poor Risk Stage III Non-Small Cell Lung Cancer [NCT00288054] | Phase 1 | 24 participants (Actual) | Interventional | 2006-04-30 | Terminated(stopped due to Study closed early due to poor accrual.) |
| Adjuvant Chemotherapy (Docetaxel and Estramustine Phosphate) for High Risk Localized Prostate Cancer [NCT00193271] | Phase 2 | 30 participants | Interventional | 2004-08-31 | Completed |
| A Multicenter, Open-Label, Randomized, Phase III Trial Comparing Immediate Adjuvant Hormonal Therapy (ELIGARD®- Leuprolide Acetate) in Combination With TAXOTERE® (Docetaxel) Administered Every Three Weeks Versus Hormonal Therapy Alone Versus Deferred Ther [NCT00283062] | Phase 3 | 228 participants (Actual) | Interventional | 2005-12-31 | Completed |
| Pilot Trial of Sequential Dose-Dense Neoadjuvant Chemotherapy Plus Herceptin in HER2 Positive Stage II-III Breast Cancer Patients [NCT00270894] | Phase 2 | 30 participants (Actual) | Interventional | 2005-11-30 | Completed |
| A Feasibility Study for Individualized Treatment of Patients With Advanced Pancreatic Cancer [NCT00276744] | Phase 2 | 249 participants (Actual) | Interventional | 2005-10-31 | Terminated(stopped due to Because there was no longer an active laboratory component to this study.) |
| A Pilot Phase II Study Evaluating the Combination of Oxaliplatin and Docetaxel With Bevacizumab as First Line Therapy in Patients With FIGO Stage IB-IV Epithelial Ovarian, Primary Peritoneal or Fallopian Tube Carcinoma [NCT00296816] | Phase 2 | 132 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Phase II Trial of Adjuvant TC (Docetaxel/Cyclophosphamide) Plus Trastuzumab in HER2-Positive Early Stage Breast Cancer Patients [NCT00493649] | Phase 2 | 493 participants (Actual) | Interventional | 2007-06-30 | Completed |
| 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 2 | 150 participants (Actual) | Interventional | 2003-10-31 | Completed |
| Phase Ⅲ Trial of Neoadjuvant Recombinant Human Endostatin, Docetaxel and Epirubicin as First-Line Therapy in Patients With Breast Cancer [NCT01479036] | Phase 3 | 800 participants (Anticipated) | Interventional | 2011-10-31 | Recruiting |
| A Multicenter Trial Evaluating the Efficacy and Safety of Nedaplatin Plus Docetaxel in Neoadjuvant Chemotherapy Followed by Nedaplatin in Concurrent Chemoradiation for Patients With Locoregionally Advanced Nasopharyngeal Carcinoma [NCT01479504] | Phase 3 | 2 participants (Anticipated) | Interventional | 2011-11-30 | Recruiting |
| A Phase III Protocol of Androgen Suppression (AS) and 3DCRT/IMRT Vs AS and 3DCTR/IMRT Followed by Chemotherapy With Docetaxel and Prednisone for Localized, High-Risk, Prostate Cancer [NCT00288080] | Phase 3 | 612 participants (Actual) | Interventional | 2005-12-31 | Completed |
| Neoadjuvant Docetaxel+Cisplatin and 5-fluorouracil (TPF) Followed by Radiotherapy+Concomitant Chemo or Cetuximab Versus Radiotherapy+Concomitant Chemo or Cetuximab in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. A Randomize [NCT01086826] | Phase 3 | 320 participants (Actual) | Interventional | 2008-03-31 | Completed |
| WEEKLY IV TOPOTECAN/DOCETAXEL COMBINATION COMPARED TO DOCETAXEL IN PATIENTS WITH PRETREATED ADVANCED NSCLC: AN OPEN-LABEL MULTICENTER RANDOMIZED PHASE III TRIAL [NCT00065182] | Phase 2 | 399 participants (Actual) | Interventional | 2003-08-14 | Completed |
| A Phase 1/2 Study of Bcl-2 Antisense Oligonucleotide G3139 in Combination With Doxorubicin and Docetaxel in Metastatic and Locally Advanced Breast Cancer [NCT00063934] | Phase 1/Phase 2 | 31 participants (Actual) | Interventional | 2003-05-31 | Terminated |
| A Phase II Study of Bevacizumab in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck [NCT00281840] | Phase 2 | 30 participants (Actual) | Interventional | 2005-09-30 | Completed |
| National Lung Matrix Trial: Multi-drug, Genetic Marker-directed, Non-comparative, Multi-centre, Multi-arm Phase II Trial in Non-small Cell Lung Cancer [NCT02664935] | Phase 2 | 423 participants (Actual) | Interventional | 2015-05-31 | Active, not recruiting |
| Phase II Pilot Trial of Dose-Dense Docetaxel Followed by Doxorubicin Plus Cyclophosphamide (T-AC) Given as Adjuvant or Neoadjuvant Treatment for Women With Node Positive or High-Risk Primary Breast Cancer [NCT00193115] | Phase 2 | 32 participants | Interventional | 2004-03-31 | Completed |
| A Phase II Trial of Weekly Docetaxel and Bortezomib (Velcade; PS-341) in the Treatment of Patients With Advanced Hormone-Refractory Prostate Cancer [NCT00193232] | Phase 2 | 50 participants | Interventional | 2004-05-31 | Completed |
| Efficacy & Safety of Bevacizumab as Neoadjuvant Treatment in Patients With Locally Advanced Inflammatory Breast Cancer, a Pilot Study. [NCT01880385] | Phase 1 | 30 participants (Anticipated) | Interventional | 2011-03-31 | Recruiting |
| A Pilot Study of Docetaxel on a Bi-Weekly Schedule in the Treatment of Elderly Men With Hormone-Refractory Prostate Cancer (HRPC) [NCT00215709] | Phase 1 | 17 participants (Actual) | Interventional | 2004-07-31 | Completed |
| Phase 2 Study of Androgen Deprivation Therapy (ADT) Plus Chemotherapy as Initial Treatment for Local Failures or Advanced Prostate Cancer [NCT02560051] | Phase 2 | 19 participants (Actual) | Interventional | 2015-11-30 | Terminated(stopped due to Slow accrual; resource re-allocation) |
| Phase I Study of Taxotere, Cisplatin, and CPT-11 in Advanced Solid Tumor Malignancies [NCT00251407] | Phase 1 | 46 participants (Actual) | Interventional | 1999-09-30 | Completed |
| A Randomized Multicenter Trial of Neoadjuvant Taxotere and Adriamycin/Cytoxan(AC): A Biologic Correlative Study [NCT00206466] | Phase 2 | 70 participants (Actual) | Interventional | 2002-04-30 | Completed |
| Phase I Study of the Oral Platinum Agent Satraplatin (JM-216) in Combination With Docetaxel in Treatment of Advanced Malignancies [NCT00125411] | Phase 1 | 28 participants (Actual) | Interventional | 2007-03-31 | Terminated(stopped due to Sponsor decided to discontinue study drug development.) |
| A PHASE II STUDY OF THE CLINICAL AND BIOLOGIC EFFECTS OF DOCETAXEL (TAXOTERE) IN PATIENTS WITH LOCALLY ADVANCED BREAST CANCER [NCT00206505] | Phase 2 | 40 participants | Interventional | 1999-01-31 | Completed |
| A Phase II Single-arm Study of AMG 386 in Combination With Docetaxel for Advanced Urothelial Carcinoma After Failure of a Platinum-containing Regimen [NCT01907308] | Phase 2 | 0 participants (Actual) | Interventional | 2014-02-28 | Withdrawn(stopped due to Sponsor's decision to terminate the study) |
| A Trail of Neoadjuvant Endostar in Combination With Docetaxel, Epirubicin and Cyclophosphamide in Patients With Stage III Breast Cancer (TENDENCY) [NCT01907529] | Phase 2/Phase 3 | 300 participants (Anticipated) | Interventional | 2019-08-31 | Enrolling by invitation |
| A Phase Ib/II Study of Docetaxel With or Without Buparlisib as Second Line Therapy for Patients With Advanced or Metastatic Squamous Non-small Cell Lung Cancer [NCT01911325] | Phase 1 | 27 participants (Actual) | Interventional | 2013-10-31 | Terminated(stopped due to Review of safety and preliminary efficacy data showed marginal anti-tumor activity.) |
| A Phase IIa, Open-Label, Multi-Center, Multi-Cohort, Immune-Modulated Study of Selected Small Molecules (Gefitinib, AZD9291, or Selumetinib + Docetaxel) or a 1st Immune-Mediated Therapy (IMT; Tremelimumab) With a Sequential Switch to a 2nd IMT (MEDI4736) [NCT02179671] | Phase 2 | 32 participants (Actual) | Interventional | 2014-07-25 | Completed |
| A Feasibility Study of De-escalation of Chemotherapy in Patients With Early-Stage HER2 Positive Breast Cancer [NCT04419181] | Phase 2 | 20 participants (Anticipated) | Interventional | 2024-08-11 | Suspended(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 Prospective Phase II Trial of Docetaxel-Samarium in Patients With Hormone-Refractory Advanced Prostate Cancer Who Achieve a Response or a Stabilization to Docetaxel-Estramustine [NCT00126230] | Phase 2 | 55 participants | Interventional | 2004-01-31 | Terminated |
| A Phase I/II Trial of ABI-008 (Nab-docetaxel) in Patients With Hormone-refractory Prostate Cancer [NCT00477529] | Phase 1/Phase 2 | 102 participants (Actual) | Interventional | 2007-04-01 | Completed |
| A Multicenter, Placebo-Controlled, Double-Blind Randomized Phase II Trial of Neoadjuvant Treatment With Single-Agent Bevacizumab or Placebo, Followed by Six Cycles of Docetaxel, Doxorubicin, and Cyclophosphamide (TAC), With or Without Bevacizumab in Patie [NCT00203372] | Phase 2 | 6 participants (Actual) | Interventional | 2005-05-31 | Completed |
| A Phase 1b/2 Study of Docetaxel and Prednisone, With or Without ISIS 183750 (an eIF4E Inhibitor), in Patients With Castrate-Resistant Prostate Cancer [NCT01234025] | Phase 1/Phase 2 | 113 participants (Actual) | Interventional | 2010-11-30 | Completed |
| A Randomized, Controlled, Open-Label, Multicenter, Phase 2 Study of Nimotuzumab Plus Docetaxel and Capecitabine Versus Docetaxel and Capecitabine as First-Line Treatment in Patients With Recurrent/Metastatic Triple Negative Breast Cancer [NCT01939054] | Phase 2 | 90 participants (Anticipated) | Interventional | 2013-09-30 | Recruiting |
| A Phase II of AT-101 in Combination With Docetaxel in Patients With Recurrent, Locally Advanced or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT01285635] | Phase 2 | 35 participants (Actual) | Interventional | 2010-06-30 | Terminated(stopped due to drug is no longer manufactured) |
| A Phase II Study of Cisplatin Plus Docetaxel as Neoadjuvant Therapy for Stages IB Through Selected IIIA NSCLC [NCT00232206] | Phase 2 | 40 participants (Anticipated) | Interventional | 2005-05-31 | Terminated(stopped due to study terminated due to slow accrual) |
| An Extension Phase II Study of the Clinical and Biologic Effects of Docetaxel (Taxotere) in Patients With Locally Advanced Breast Cancer [NCT00206453] | Phase 2 | 25 participants (Actual) | Interventional | 2002-01-31 | Terminated(stopped due to accrual too difficult to meet) |
| A Phase 1-2 Study of OR2805, a Monoclonal Antibody Targeting CD163, Alone and in Combination With Anticancer Agents in Subjects With Advanced Malignancies [NCT05094804] | Phase 1/Phase 2 | 172 participants (Anticipated) | Interventional | 2021-09-09 | Recruiting |
| Phase I/II Study of Docetaxel, Cisplatin and 5-fluorouracil(TPF) as 1st-line Chemotherapy in Patients With Metastatic Esophageal Cancer. [NCT00209690] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2003-10-31 | Completed |
| A Phase II Single-arm Study of Tazemetostat With Docetaxel, Cisplatin, and 5-fluorouracil as Preoperative Treatment for Locally Advanced Potentially Resectable SMARCB1 (INI-1)- Deficient Sinonasal Carcinoma [NCT05151588] | Phase 2 | 30 participants (Anticipated) | Interventional | 2023-09-01 | Not yet recruiting |
| A Dose-finding Trial of Hyperthermic Intraperitoneal Docetaxel and Cisplatin in Patients Receiving Hyperthermic Intraperitoneal Chemotherapy [NCT05410483] | Phase 1 | 30 participants (Anticipated) | Interventional | 2022-03-01 | Recruiting |
| Docetaxel and Cisplatin Chemotherapy Followed by Radiochemotherapy in Patients With Inoperable, Locally Advanced Esophageal Cancer, A Multicenter Phase II Trial [NCT00238407] | Phase 2 | 21 participants (Actual) | Interventional | 2004-03-31 | Completed |
| 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 1 | 40 participants (Actual) | Interventional | 2004-05-31 | Completed |
| A Phase II Trial of Combination Therapy With Celecoxib and Taxotere for the Treatment of Stage D3 Prostate Cancer [NCT00215345] | Phase 2 | 66 participants | Interventional | 2002-08-31 | Recruiting |
| Phase II Pharmacogenomic Study of Neoadjuvant Pre-irradiation Docetaxel and Cisplatin, Followed by Neoadjuvant Concomitant Docetaxel, Cisplatin and Irradiation, Followed by Surgery (CD-CDR-S) in Adult Patients With Operable Adenocarcinomas of the Esophagu [NCT00216008] | Phase 2 | 42 participants | Interventional | 2005-07-31 | Terminated(stopped due to IRB Closure) |
| Multicenter Phase II Trial of Oxaliplatin and Docetaxel for Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck [NCT00557206] | Phase 2 | 35 participants (Actual) | Interventional | 2005-04-30 | Terminated(stopped due to Funding was terminated) |
| 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 2 | 0 participants | Interventional | 2004-06-30 | Completed |
| 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 2 | 0 participants | Interventional | 2005-05-31 | Completed |
| Phase I Trial With a Combination of Docetaxel +153 Sm-EDTMP (Samarium 153) in Patients With Hormone-Refractory Prostate Cancer [NCT00559429] | Phase 1 | 13 participants (Actual) | Interventional | 2004-12-31 | Completed |
| A Phase II Study of MEDI4736 for Previously Treated Patients With Stage IV Squamous Cell Lung Cancer and No Matching Biomarkers (Lung-Map Sub-Study) [NCT02766335] | Phase 2/Phase 3 | 116 participants (Actual) | Interventional | 2014-07-31 | Completed |
| A Phase II Study of Irinotecan and Taxotere With Concurrent Radiotherapy as a Preoperative Treatment in Resectable Esophageal Cancer [NCT00318903] | Phase 2 | 25 participants (Actual) | Interventional | 2002-01-31 | Completed |
| [NCT00243204] | Phase 3 | 400 participants (Anticipated) | Interventional | 2006-01-31 | Terminated(stopped due to FDA Hold May 2007) |
| A Phase I, Open-Label, Randomized, Two Period Crossover Study to Investigate the Effects of GW679769 on the Pharmacokinetics of Docetaxel in Subjects With Cancer [NCT00440128] | Phase 1 | 12 participants (Actual) | Interventional | 2007-05-04 | Completed |
| A Phase 1b Study of Vantictumab (OMP-18R5) in Combination With Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer [NCT01957007] | Phase 1 | 34 participants (Anticipated) | Interventional | 2013-09-30 | Completed |
| An Open Label, Randomized Study to Evaluate Safety and Pharmacokinetics of Intravenous Infusion of Nanosomal Docetaxel Lipid Suspension for Injection in Patients With Advanced Solid Tumors [NCT01957995] | Phase 1 | 13 participants (Actual) | Interventional | 2013-11-08 | Completed |
| A Pilot Safety and Toxicity Trial of Adjuvant Chemotherapy With Gemcitabine and Docetaxel and Radiation Therapy for Completely Resected Uterine Leiomyosarcoma [NCT01958580] | | 3 participants (Actual) | Interventional | 2013-09-17 | Terminated(stopped due to Study terminated due to low accrual. PI left the institution) |
| A Phase 2, Randomized, Open-Label, Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer [NCT05848011] | Phase 2 | 150 participants (Anticipated) | Interventional | 2023-09-28 | Recruiting |
| Phase II Trial of Exploring the Predictive Factors of Docetaxol Plus Capecitabine(TX) Regimen and Oxaliplatin Plus Capecitabine (XELOX) Regimen in the First Line Treatment of Patients With Metastatic Gastric Cancer (MGC) [NCT01963702] | Phase 2 | 120 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| 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 3 | 174 participants (Actual) | Interventional | 2014-02-21 | Completed |
| A Phase 2 Platform Study Evaluating the Safety and Efficacy of Novel Treatment Combinations in Patients With Lung Cancer (VELOCITY-Lung) [NCT05633667] | Phase 2 | 397 participants (Anticipated) | Interventional | 2023-03-16 | Recruiting |
| A Phase 1, Open-label, Multicenter Study of BMS-986360/CC-90001 Alone and in Combination With Chemotherapy or Nivolumab in Advanced Solid Tumors [NCT05625412] | Phase 1 | 220 participants (Anticipated) | Interventional | 2022-12-09 | Recruiting |
| A Prospective, Multi-Center, Randomized Control Phase 2 Trial of Optimizing Platinum-Based Chemotherapy Based on ERCC1 Expression as First-Line Treatment in Patients With Locally Advanced or Metastatic Gastric Cancer [NCT01967875] | Phase 2 | 27 participants (Actual) | Interventional | 2013-07-31 | Terminated(stopped due to slow enrollment) |
| A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Giredestrant in Combination With Phesgo Versus Phesgo After Induction Therapy With Phesgo + Taxane in Patients With Previously Untreated HER2-Positive, Estrogen Receptor-Posit [NCT05296798] | Phase 3 | 812 participants (Anticipated) | Interventional | 2022-07-04 | Recruiting |
| A Phase 3, Randomized, Double-Blind Study of Nivolumab or Placebo in Combination With Docetaxel, in Men With Metastatic Castration-resistant Prostate Cancer [NCT04100018] | Phase 3 | 984 participants (Anticipated) | Interventional | 2020-02-06 | Active, not recruiting |
| Sequential Therapy With Induction TPN Followed by Nivolumab With Radiation in Locoregionally Advanced Laryngeal and Hypopharyngeal Cancer [NCT03894891] | Phase 2 | 6 participants (Actual) | Interventional | 2019-06-11 | Completed |
| A Multicenter Randomized Study Comparing the Dose Dense, G-CSF-supported Sequential Administration of FE75C Followed by Docetaxel Versus Docetaxel/Cyclophosphamide Doublet as Adjuvant Chemotherapy in Women With HER-2 Negative, Axillary Lymph Node Positive [NCT01985724] | Phase 3 | 650 participants (Actual) | Interventional | 2007-10-31 | Completed |
| Phase II, Open-label Non-randomized Trial to Investigate the Efficacy of Bevacizumab in Combination With Dose Dense Sequential Chemotherapy in the Neo-adjuvant Setting for HER2 Negative Breast Cancer Patients [NCT01985841] | Phase 2 | 34 participants (Actual) | Interventional | 2011-10-31 | Terminated(stopped due to Due to poor accrual) |
| A Combined Phase I/II Feasibility-and-Efficacy Study of a Carbohydrate Mimotope-based Vaccine With MONTANIDE™ ISA 51 VG Combined With Neoadjuvant Chemotherapy [NCT02229084] | Phase 1/Phase 2 | 50 participants (Actual) | Interventional | 2015-01-14 | Completed |
| Single-center Randomized Study Evaluating of Oncological Benifits of Pressured Intraperitoneal Aerosol Chemotherapy (PIPAC) in Patients With Locally Advanced Gastric Cancer in Patients With Cyt-. [NCT04595929] | | 304 participants (Anticipated) | Interventional | 2020-02-10 | Recruiting |
| A Phase II Study of MAOA Inhibitor Plus Docetaxel in Patients Receiving and Progressing on Docetaxel Therapy [NCT01253642] | Phase 2 | 11 participants (Actual) | Interventional | 2010-07-12 | Terminated(stopped due to low enrollment) |
| Phase I Trial of Daily Lenalidomide (CC-5013, Revlimid™) and Docetaxel Given Every Three Weeks in Patients With Advanced Solid Tumors [NCT00253344] | Phase 1 | 33 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Comparison of Postoperative Adjuvant Chemotherapy With/Without Rh-endostatin: a Randomized, PhaseⅢ and Open Clinical Study of Non-small Cell Lung Cancer in PhaseⅠB [NCT02001168] | Phase 3 | 392 participants (Anticipated) | Interventional | 2013-10-31 | Active, not recruiting |
| A Randomized Phase III Trial of Neoadjuvant Chemotherapy With 3 Cycles of FEC Followed by 3 Cycles of Docetaxel Versus 4 Cycles of Adriamycin Plus Cyclophosphamide Followed by 4 Cycles of Docetaxel in Node-positive Breast Cancer [NCT02001506] | Phase 3 | 250 participants (Actual) | Interventional | 2012-11-30 | Completed |
| Adjuvant Treatment of EC/TC Versus EC/TC Plus Danggui Buxue Decoction in Breast Cancer：A Prospective, Randomized Trial [NCT02005783] | Phase 2 | 50 participants (Anticipated) | Interventional | 2013-10-31 | Completed |
| Phase II Study of Capecitabine and Weekly Docetaxel Followed by Capecitabine Maintenance for Patients With Metastatic Breast Carcinoma [NCT00225056] | Phase 2 | 43 participants | Interventional | 2003-10-31 | Terminated(stopped due to Terminated due to lack of accrual) |
| A Phase I Study Using Low Dose Abdominal Radiotherapy as A Docetaxel Chemosensitizer for Recurrent , Persistent Or Advanced Ovarian, Peritoneal Or Fallopian Tube Cancer [NCT00066456] | Phase 1 | 13 participants (Actual) | Interventional | 2003-09-30 | Completed |
| A Phase II Study to Measure Response Rate and Toxicity of Neo-adjuvant Chemoradiotherapy With Oxaliplatin (OX) and Infusional 5-Fluorouracil (5-FU) Plus Cetuximab Followed by Post-Operative Docetaxel and Cetuximab in Patients With Operable Adenocarcinoma [NCT00551759] | Phase 2 | 22 participants (Actual) | Interventional | 2008-10-02 | Terminated(stopped due to The study used a two-stage design. After stage one, the study was terminated due to excess toxicity.) |
| A Multicenter, Single Arm, Open-Label PhIV Study to Investigate the Effect of First-Line Herceptin (Trastuzumab) in Combination With a Taxane in Patients With Metastatic Breast Cancer Who Relapsed After Receiving (Neo)Adjuvant Herceptin for HER2-Positive [NCT01301729] | Phase 4 | 32 participants (Actual) | Interventional | 2011-03-31 | Completed |
| A Phase 3, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of BGB-A317 (Anti-PD1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer Who Have Progressed on a Prior Platinum-Containing Regimen [NCT03358875] | Phase 3 | 805 participants (Actual) | Interventional | 2017-11-30 | Active, not recruiting |
| A Phase I Trial of Apalutamide Plus Abiraterone Acetate, Docetaxel, and Prednisone in Patients With Metastatic Castrate Resistant Prostate Cancer (mCRPC) [NCT02913196] | Phase 1 | 16 participants (Actual) | Interventional | 2016-12-30 | Active, not recruiting |
| MetronomIc CApecitabine and DOcetaxel as Second-line Chemotherapy for Advanced Gastric Cancer Patients Previously Treated With Fluoropyrimidine and Platinum Agents MiCADO Study [NCT02007148] | Phase 2 | 51 participants (Anticipated) | Interventional | 2013-11-30 | Recruiting |
| Treatment of Patients With Transitional-Cell Carcinoma of the Urothelial Tract With Gemcitabine, Docetaxel and Filgrastim [NCT00005958] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Active, not recruiting |
| A Phase I/IIA Dose-Escalating Trial of BCL-2 Antisense (G3139) Treatment for Patients With Androgen-Independent Prostate Cancer or Other Advanced Solid Tumor Malignancies [NCT00003103] | Phase 1/Phase 2 | 57 participants (Anticipated) | Interventional | 1997-08-31 | Completed |
| A Phase II Randomized - Non Comparative - Study on the Activity of Trabectedin or Gemcitabine + Docetaxel in Metastatic or Locally Relapsed Uterine Leiomyosarcoma Pretreated With Conventional Chemotherapy [NCT02249702] | Phase 2 | 168 participants (Actual) | Interventional | 2010-04-30 | Completed |
| An Open-Label Phase I/II Clinical Study of PT-112 in Combination With Docetaxel in Subjects With Advanced Solid Tumor in a Phase I Dose Escalation Study and in Subjects With Non-Small Cell Lung Cancer (NSCLC) in a Phase II Dose Confirmation Study [NCT02884479] | Phase 1/Phase 2 | 75 participants (Anticipated) | Interventional | 2016-08-31 | Recruiting |
| Phase II Study Comparing Gemcitabine Plus Cisplatin to Docetaxel, Cisplatin, and Fluorouracil Induction Chemotherapy Followed by Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma [NCT02016417] | Phase 2 | 120 participants (Anticipated) | Interventional | 2014-05-31 | Not yet recruiting |
| Phase II, Single Arm, Single Institution Clinical Trial of Docetaxel and Doxorubicin in Combination With Local Administration of INGN 201 (Ad5CMV-p53) in Locally Advanced Breast Cancer (LABC) [NCT00044993] | Phase 2 | 0 participants | Interventional | 2002-02-28 | Completed |
| Phase II Trial of Neoadjuvant Recombinant Human Endostatin, Docetaxel and Epirubicin as First-line Therapy in Patients With Breast Cancer [NCT00604435] | Phase 2 | 69 participants (Actual) | Interventional | 2008-02-29 | Completed |
| Phase 3, Randomized, Open-label Study Of The Efficacy And Safety Of Pf-02341066 Versus Standard Of Care Chemotherapy (Pemetrexed Or Docetaxel) In Patients With Advanced Non-small Cell Lung Cancer (Nsclc) Harboring A Translocation Or Inversion Event Involv [NCT00932893] | Phase 3 | 347 participants (Actual) | Interventional | 2009-09-30 | Completed |
| Feasibility Study of Intraperitoneal Docetaxel Combined With Intravenous Cisplatin and Oral TS-ONE for Gastric Cancer Patients With Peritoneal Carcinomatosis [NCT02024841] | Phase 1 | 12 participants (Actual) | Interventional | 2013-12-31 | Completed |
| 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 1 | 59 participants (Actual) | Interventional | 2009-07-31 | Completed |
| A Phase II Study of Docetaxel and Carboplatin as Second Line Chemotherapy in First Relapse of Platinum Sensitive Epithelial Ovarian Cancer [NCT02026921] | Phase 2 | 74 participants (Actual) | Interventional | 2004-06-30 | Completed |
| 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 2 | 18 participants (Actual) | Interventional | 2018-08-24 | Active, not recruiting |
| Allogeneic Transplantation Using Mini-Conditioning for Treatment of Stage IV Breast Cancer [NCT00006261] | Phase 2 | 0 participants (Actual) | Interventional | 2000-05-31 | Withdrawn |
| Randomized Phase II Trial of Herceptin (NSC 688097) and Weekly Docetaxel (NSC 628503) in Androgen-Independent (Horomone Refractory) Adenocarcinoma of the Prostate (CaP) [NCT00005857] | Phase 2 | 0 participants | Interventional | 2000-08-31 | Completed |
| Impact of Neoadjuvant Chemotherapy With or Without Zometa on Occult Micrometastases and Bone Density in Women With Locally Advanced Breast Cancer [NCT00242203] | Phase 2 | 120 participants (Actual) | Interventional | 2002-10-31 | Completed |
| A Randomized Phase II Study on the OPTimization of IMmunotherapy in Squamous Carcinoma of the Head and Neck [NCT03620123] | Phase 2 | 54 participants (Actual) | Interventional | 2018-07-16 | Completed |
| Phase II Trial of Gemcitabine and Docetaxel in Patients With Unresectable or Metastatic Hepatocellular Carcinoma [NCT00006010] | Phase 2 | 25 participants (Actual) | Interventional | 2001-09-30 | Completed |
| Phase I Dose-Escalation Parallel Studies of Intraperitoneal Oxaliplatin With Intravenous Docetaxel and Intravenous Oxaliplatin With Intraperitoneal Docetaxel in Platinum-Sensitive or Platinum-Resistant Recurrent Ovarian, Primary Peritoneal, and Fallopian [NCT00692900] | Phase 1 | 25 participants (Actual) | Interventional | 2008-12-31 | Completed |
| Neoadjuvant Durvalumab (MEDI4736) Plus Docetaxel, Oxaliplatin, S-1 (DOS) Followed by Surgery and Adjuvant Durvalumab Plus S-1 Chemotherapy in Potentially Resectable MMR Proficient (pMMR) Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma [NCT04221555] | Phase 2 | 68 participants (Anticipated) | Interventional | 2020-05-13 | Recruiting |
| A Randomized, Controlled, Open-label, Global Phase 3 Study Comparing the Efficacy of the Anti-PD-1 Antibody Tislelizumab (BGB-A317) Versus Chemotherapy as Second Line Treatment in Patients With Advanced Unresectable/Metastatic Esophageal Squamous Cell Car [NCT03430843] | Phase 3 | 512 participants (Actual) | Interventional | 2018-01-26 | Completed |
| A Phase II Clinical Study of SHR3680 Combined With Docetaxel in the Treatment of Metastatic Castration-resistant Prostate Cancer Previously Treated With Abiraterone [NCT04603833] | Phase 2 | 150 participants (Anticipated) | Interventional | 2020-12-02 | Recruiting |
| A Phase I Study of Suberoylanilide Hydroxamic Acid (Vorinostat) (NSC 701852) in Combination With Docetaxel in Patients With Advanced and Relapsed Solid Malignancies [NCT00565227] | Phase 1 | 12 participants (Actual) | Interventional | 2007-04-30 | Terminated(stopped due to closed due to toxicity) |
| A Study on the Efficacy and Safety of Anlotinib Combined With Docetaxel in the Treatment of Wild-type Advanced Non-squamous Non Small Cell Lung Cancer Patients With Progress After Immunotherapy Plus Chemotherapy as First-line Treatment [NCT04619537] | Phase 2 | 42 participants (Anticipated) | Interventional | 2020-10-08 | Recruiting |
| Phase II Study of Weekly Docetaxol Combined With Cisplatin and 5-Fu in Patients With Advanced Gastric Cancer [NCT00568971] | Phase 2 | 40 participants (Actual) | Interventional | 2007-04-30 | Terminated(stopped due to The study has finished.) |
| A Phase III Trials Program Exploring the Integration of Bevacizumab, Everolimus (RAD001), and Lapatinib Into Current Neoadjuvant Chemotherapy Regimes for Primary Breast Cancer [NCT00567554] | Phase 3 | 2,600 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Clinical Trial of Selegiline Plus Docetaxel for the Treatment of Metastatic, Castrate-resistant Prostate Adenocarcinoma [NCT04586543] | Phase 2 | 110 participants (Anticipated) | Interventional | 2020-05-18 | Recruiting |
| Phase II Evaluation of Docetaxel Randomized With Doxercalciferol or Placebo in Patients With Advanced Prostate Cancer [NCT00582582] | Phase 2 | 70 participants (Actual) | Interventional | 2002-04-30 | Terminated(stopped due to Lack of drug supply for doxercalciferol for this study) |
| Efficacy and Safety of Dose-dense Epirubicin and Cyclophosphamide Plus Paclitaxel as Neoadjuvant Chemotherapy for HER2-negative Early Breast Cancer：a Multicenter Randomized Controlled Trial [NCT04576143] | Phase 2/Phase 3 | 260 participants (Anticipated) | Interventional | 2020-09-20 | Recruiting |
| Phase Ib/II Evaluation of RAD001 With Docetaxel and Bevacizumab in Patients With Metastatic Androgen Independent Prostate Cancer [NCT00574769] | Phase 1/Phase 2 | 27 participants (Actual) | Interventional | 2010-02-17 | Completed |
| Phase II Study of Perioperative S-1 Plus Docetaxel in Patients With Localized Advanced Gastric Cancer [NCT00587145] | Phase 2 | 44 participants (Anticipated) | Interventional | 2006-05-31 | Recruiting |
| Phase II Trial of Induction Chemotherapy With Weekly Gemcitabine, Epirubicin, Docetaxel as Primary Treatment of Locally Advanced or Inflammatory Breast Cancer Patients [NCT00193050] | Phase 2 | 110 participants (Actual) | Interventional | 2001-11-30 | Completed |
| A Randomized Study of Gemcitabine Plus Docetaxel After Cisplatin, Etoposide and Radiation Therapy in Stage III Unresectable NSCLC [NCT00191139] | Phase 2 | 64 participants (Actual) | Interventional | 2003-03-31 | Completed |
| A Randomized, Placebo-Controlled, Double-Blind, Phase 3 Study Evaluating the Pain Palliation Benefit of Adding Custirsen to a Taxane for Second-Line Chemotherapy in Men With Castrate Resistance Prostate Cancer [NCT01083615] | Phase 3 | 14 participants (Actual) | Interventional | 2010-03-31 | Terminated(stopped due to Unable to enroll due to criteria for stable baseline pain) |
| A Randomized, Open-label, Multi-center Phase II Study to Compare AUY922 With Docetaxel or Irinotecan in Adult Patients With Advanced Gastric Cancer, Who Have Progressed After One Line of Chemotherapy [NCT01084330] | Phase 2 | 68 participants (Actual) | Interventional | 2010-04-30 | Completed |
| Toripalimab Combined With Docetaxel or Nab-paclitaxel in the Treatment of Advanced Gastric Cancer : a Single-arm, Open Label, Prospective Phase II Clinical Trial [NCT04563975] | Phase 2 | 54 participants (Anticipated) | Interventional | 2020-07-02 | Recruiting |
| An Open-label Study of the Effect of First-line Herceptin Alone or in Combination With a Taxane on Tumor Response and Disease Progression in Patients With Metastatic Breast Cancer Who Relapsed After Receiving Adjuvant Herceptin for HER2-positive Early Bre [NCT00475670] | Phase 2 | 44 participants (Actual) | Interventional | 2005-10-31 | Completed |
| An Open-label Phase 1/2 Study of TAK-700 in Combination With Docetaxel and Prednisone in Men With Metastatic Castration-Resistant Prostate Cancer [NCT01084655] | Phase 1/Phase 2 | 38 participants (Actual) | Interventional | 2010-07-31 | Completed |
| An Open-label, Multi-centre Study of Lapatinib in Combinationwith Chemotherapy in Patients With ErbB2 Overexpressing Breastcancer After Trastuzumab Failure in the Neoadjuvant or Adjuvantsetting. [NCT00479856] | Phase 2 | 9 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to Study was terminated due to difficulty in identifying eligible subjects) |
| A Phase III, Multicenter, Randomized, Open-Label, Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Atezolizumab Given in Combination With Cabozantinib Versus Docetaxel Monotherapy in Patients With Metastatic Non-Small Lung Cancer [NCT04471428] | Phase 3 | 366 participants (Actual) | Interventional | 2020-10-01 | Active, not recruiting |
| Randomized Phase II Trial of Extended Neoadjuvant Therapy for Locally Advanced Adenocarcinoma of the Esophagus, Gastroesophageal Junction, and Gastric Cardia [NCT00938470] | Phase 2 | 73 participants (Actual) | Interventional | 2010-01-31 | Completed |
| Preoperative Chemotherapy and Radiotherapy Concomitant to Cetuximab in Non-Small Cell Lung Cancer (NSCLC) Patients With IIIB Disease - A Multicenter Phase II Trial [NCT01059188] | Phase 2 | 69 participants (Actual) | Interventional | 2010-05-03 | Completed |
| Detecting Chemosensitivity and Predicting Treatmemt Efficacy With Circulating Tumour Cells From Peripheral Blood in Metastatic Nasopharyngeal Carcinoma Patients [NCT04544969] | | 50 participants (Anticipated) | Observational [Patient Registry] | 2020-04-01 | Recruiting |
| Concurrent Chemoradiotherapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck Versus Concomitant Cetuximab With Radiotherapy After Neoadjuvant Chemotherapy: a Randomized, Opened, Multicenter Phase II Trial [NCT02753140] | Phase 2 | 60 participants (Anticipated) | Interventional | 2016-04-30 | Not yet recruiting |
| A Phase II Study of Robotic Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Patients With Gastric Cancer and Limited Peritoneal Metastasis: ROBO-CHIP Trial [NCT05753306] | Phase 2 | 20 participants (Anticipated) | Interventional | 2023-03-16 | Recruiting |
| A Multicenter Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LBL-007 in Combination With Tislelizumab in the Treatment of Malignancies [NCT05516914] | Phase 1/Phase 2 | 490 participants (Anticipated) | Interventional | 2022-09-01 | Recruiting |
| A Controlled, Randomized Phase II Trial of Docetaxel Plus Trastuzumab Versus Ado-Trastuzumab Emtansine for Recurrent, Metastatic, or Treatment-Naive, Unresectable HER2-Positive Salivary Gland Cancer [NCT05408845] | Phase 2 | 116 participants (Anticipated) | Interventional | 2022-09-30 | Recruiting |
| An Open-Label, Phase Ib Study to Assess the Safety and Tolerability of GSK1120212 in Combination With Docetaxel in Japanese Subjects With Non-small Cell Lung Cancer [NCT01938456] | Phase 1 | 0 participants (Actual) | Interventional | 2013-10-31 | Withdrawn(stopped due to This study was Cancelled Before Active) |
| Phase II Study of Efficacy and Safety Evaluation of KN026 Monotherapy or Combination Therapy in Patients With HER2 Expressing or Positive Metastatic Breast Cancer [NCT04165993] | Phase 2 | 68 participants (Actual) | Interventional | 2019-12-31 | Active, not recruiting |
| A Randomized Phase II Trial Comparing Biomarker Directed Therapy Versus Clinician's Choice of Enzalutamide or Docetaxel in Patients With Advanced Prostate Cancer Post Abiraterone [NCT04015622] | Phase 2 | 100 participants (Anticipated) | Interventional | 2020-10-07 | Recruiting |
| Phase III Randomized Trial of Proton Beam Therapy (PBT) Versus Intensity Modulated Photon Radiotherapy (IMRT) for the Treatment of Esophageal Cancer [NCT03801876] | Phase 3 | 300 participants (Anticipated) | Interventional | 2019-03-15 | Recruiting |
| A Phase 3, Multicenter, Randomized, Open-Label, Active-Controlled Trial Of JSKN003 Versus Treatment Of Physician'S Choice For HER2-low, Unresectable and/or Metastatic Breast Cancer Subjects [NCT06079983] | Phase 3 | 400 participants (Anticipated) | Interventional | 2023-12-01 | Not yet recruiting |
| A Randomised Phase III Open Label Study of Regorafenib + Nivolumab vs Standard Chemotherapy in Refractory Advanced Gastro-Oesophageal Cancer (AGOC) [NCT04879368] | Phase 3 | 450 participants (Anticipated) | Interventional | 2021-06-01 | Recruiting |
| A Phase I Study of Continuous, Concomitant Oral Treatment With BIBF 1120 and Docetaxel - a Phase I, Open-label, Dose-escalation Study in Japanese Patients With Stage IIIB/IV or Recurrent Non-small-cell Lung Cancer After Failure of Chemotherapy [NCT00876460] | Phase 1 | 43 participants (Actual) | Interventional | 2009-03-31 | Completed |
| 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 2 | 31 participants (Actual) | Interventional | 2008-06-16 | Active, not recruiting |
| Combination of Docetaxel + Estramustine + Hydrocortisone Versus Docetaxel + Prednisone in Patients With Advanced Prostate Cancer Who Have Relapse in Biochemistry Whilst Androgenic Blockage [NCT00705822] | Phase 3 | 54 participants (Actual) | Interventional | 2006-08-31 | Terminated(stopped due to low recruitment rate) |
| Multicenter Phase II Study of Weekly Docetaxel, Cisplatin, and S-1 (TPS) Induction Chemotherapy in Locally Advanced Squamous Cell Cancer of the Head and Neck [NCT01645748] | Phase 2 | 35 participants (Actual) | Interventional | 2008-10-31 | Completed |
| A Trial Comparing Pre-operative Chemo-radiotherapy With Cisplatin and Fluorouracil Versus Chemotherapy With Docetaxel and Irinotecan in PET Non Responders Resectable Cancer Esophagus: a Multicenter Study [NCT01608464] | Phase 2 | 170 participants (Actual) | Interventional | 2012-05-31 | Terminated(stopped due to poor accrual) |
| A Randomized Phase III Study Comparing Trastuzumab Plus Docetaxel (HT) Followed by 5-FU, Epirubicin, and Cyclophosphamide (FEC) to the Same Regimen Followed by Single-agent Trastuzumab as Adjuvant Treatments for Early Breast Cancer [NCT00593697] | Phase 3 | 2,168 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Phase I Trial of Irinotecan, Radiation Therapy and Escalating Doses of Docetaxel With Cisplatin in Locally Advanced Esophageal Cancer [NCT00601692] | Phase 1 | 27 participants (Actual) | Interventional | 2003-04-30 | Completed |
| Phase II Trial of Weekly Docetaxel (Taxotere®) and Monthly Cisplatin Chemotherapy as Adjuvant Treatment for Patients With Completely Resected Non-small Cell Lung Cancer [NCT00281970] | Phase 2 | 50 participants (Anticipated) | Interventional | 2004-08-31 | Completed |
| "Phase II Pilot Study Evaluating the Neoadjuvant Combination Taxotere (Docetaxel) and Erbitux (Cetuximab) in Operable and Triple Negative Breast Cancer Patients. TENEO Study." [NCT00600249] | Phase 2 | 35 participants (Anticipated) | Interventional | 2008-01-31 | Completed |
| Effects of Chemotherapy on Brain Structure and Function [NCT00755313] | | 81 participants (Actual) | Observational | 2007-05-31 | Completed |
| A Randomized, Open-Label, Phase III Study of Taxane Based Chemotherapy With Lapatinib or Trastuzumab as First-Line Therapy for Women With HER2/Neu Positive Metastatic Breast Cancer [NCT00667251] | Phase 3 | 652 participants (Actual) | Interventional | 2008-10-07 | Completed |
| Phase II Study of Induction Checkpoint Blockade for Untreated Stage I-IIIA Non-Small Cell Lung Cancers Amenable for Surgical Resection [NCT03158129] | Phase 2 | 101 participants (Actual) | Interventional | 2017-06-09 | Active, not recruiting |
| Randomized, Controlled Study Comparing the Efficacy and Safety of Docetaxel （60mg/m2）Maintenance Treatment vs. Best Supportive Care Following First Line Chemotherapy With Different Doses of Docetaxel（75/60mg/m2）in Combination With Cisplatin in Patients Wi [NCT01038661] | Phase 3 | 375 participants (Actual) | Interventional | 2009-11-30 | Completed |
| A Phase I Study of RAD001 (Everolimus) + Docetaxel + Cisplatin as Induction Chemotherapy in Patients With Local-Regional Advanced Head and Neck Cancer [NCT00935961] | Phase 1 | 18 participants (Actual) | Interventional | 2009-07-31 | Completed |
| Phase II Study of Neoadjuvant Taxotere, Cisplatin, and 5-Fluorouracil in Patients With Gastric or Gastroesophageal Junction Adenocarcinoma [NCT00763646] | Phase 2 | 30 participants (Anticipated) | Interventional | 2007-04-30 | Recruiting |
| A Randomized Double-Blind Phase 3 Trial Comparing Docetaxel Combined With Dasatinib to Docetaxel Combined With Placebo in Castration-Resistant Prostate Cancer [NCT00744497] | Phase 3 | 1,930 participants (Actual) | Interventional | 2008-10-31 | Completed |
| Multicentre, Randomised, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral BIBF 1120 Plus Standard Docetaxel Therapy Compared to Placebo Plus Standard Docetaxel Therapy in Patients With Stage IIIB/IV or Recurrent Non Small Cell [NCT00805194] | Phase 3 | 1,314 participants (Actual) | Interventional | 2008-12-03 | Completed |
| A Randomized, Double-blind, Multicenter, Phase 2 Study of a Human Monoclonal Antibody to Human av Integrins (CNTO 95) in Combination With Docetaxel for the First-Line Treatment of Subjects With Metastatic Hormone Refractory Prostate Cancer [NCT00537381] | Phase 2 | 131 participants (Actual) | Interventional | 2007-05-31 | Completed |
| A Randomized/Open Label/Parallel Group/Multicenter/Phase IV Study to Assess Safety/Tolerability/Efficacy of Oral Gefitinib 250 mg Versus IV Docetaxel 60 mg/m2 in Patients With Locally Advanced or Metastatic NSCL Cancer of Adenocarcinoma Histology Previous [NCT00536107] | Phase 4 | 14 participants (Actual) | Interventional | 2007-10-31 | Terminated |
| a Prospective Random Study on the Efficacy and Safety of Bevacizumab in Untreated Patients With Locally Advanced Cervical Cancer [NCT04138992] | Phase 2/Phase 3 | 150 participants (Anticipated) | Interventional | 2020-08-01 | Recruiting |
| An Open-label, Randomized, Parallel-group, Multicenter Study of Neoadjuvant Docetaxel(Taxotere®) Plus Cisplatin Plus 5-fluorouracil Versus Neoadjuvant Cisplatin Plus 5-fluorouracil in Patients With Locally Advanced Inoperable Squamous Cell Carcinoma of th [NCT00995293] | Phase 3 | 240 participants (Actual) | Interventional | 2009-08-27 | Completed |
| A Phase II Study to Evaluate the Efficacy and Safety of Docetaxel-PM in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma [NCT02639858] | Phase 2 | 31 participants (Anticipated) | Interventional | 2015-10-31 | Recruiting |
| Phase II Study of the Gemzar, Taxotere and Xeloda Regimen (GTX) for Inoperable or Metastatic Adenocarcinoma of the Biliary System [NCT00868998] | Phase 2 | 4 participants (Actual) | Interventional | 2005-08-31 | Terminated(stopped due to Poor patient accrual) |
| Phase II Trial of Erlotinib in Combination With Docetaxel in Advanced Hepatocellular and Biliary Tract Carcinomas: Hoosier Oncology Group GI06-101 [NCT00532441] | Phase 2 | 25 participants (Actual) | Interventional | 2007-09-30 | Terminated(stopped due to Terminated due to funding issues.) |
| The Effect of Pharmacogenetics on Treatment Toxicities and Outcomes in East Asian and Caucasian Patients Undergoing Docetaxel or Gemcitabine-based Chemotherapy [NCT00695994] | Phase 2 | 300 participants (Actual) | Interventional | 2006-10-31 | Completed |
| Randomized Study of Docetaxel +/- Vandetanib in Metastatic TCC [NCT00880334] | Phase 2 | 149 participants (Actual) | Interventional | 2006-09-30 | Completed |
| 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 2 | 75 participants (Actual) | Interventional | 2004-04-30 | Completed |
| Optimizing and Personalising Azacitidine Combination Therapy for Treating Solid Tumours Using the Quadratic Phenotypic Optimization Platform (QPOP) and an Artificial Intelligence-based Platform (CURATE.AI) [NCT05381038] | Phase 1/Phase 2 | 10 participants (Anticipated) | Interventional | 2022-06-30 | Not yet recruiting |
| Phase 1/2 Study of Anti-PD-L1 in Combination With Chemo(Radio)Therapy for Oesophageal Cancer [NCT02735239] | Phase 1/Phase 2 | 73 participants (Actual) | Interventional | 2016-06-24 | Completed |
| SHORT-HER: MULTICENTRIC RANDOMISED PHASE III TRIAL OF 2 DIFFERENT ADJUVANT CHEMOTHERAPY REGIMENS PLUS 3 VS 12 MONTHS OF TRASTUZUMAB IN HER2 POSITIVE BREAST CANCER PATIENTS [NCT00629278] | Phase 3 | 2,500 participants (Anticipated) | Interventional | 2007-12-31 | Recruiting |
| A Phase I, Open-label, Dose-escalation Study of Apatinib in Combination With Docetaxel as 2nd Line Treatment in Patients With Advanced Lung Adenocarcinoma Harboring Wild-type Epidermal Growth Factor Receptor (EGFR) [NCT02691871] | Phase 1 | 20 participants (Anticipated) | Interventional | 2016-02-29 | Not yet recruiting |
| A Randomized Phase II Trial of Erlotinib or Intermittent Dosing of Erlotinib and Docetaxel in Male Former-smokers With Locally Advanced or Metastatic Squamous NSCLC in Second-line Setting After Failure on Chemotherapy [NCT01204697] | Phase 2 | 74 participants (Actual) | Interventional | 2010-11-30 | Completed |
| Sequential Cisplatin/Vinorelbine/Bevacizumab Followed by Docetaxel/Gemcitabine/Bevacizumab Versus Cisplatin/Docetaxel/Bevacizumab in Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer [NCT00620971] | Phase 2 | 77 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Phase I Study of IPI-504 and Docetaxel in Patients With Advanced Solid Tumors [NCT00606814] | Phase 1 | 60 participants (Actual) | Interventional | 2007-12-31 | Completed |
| Phase II Trial of Gemcitabine and Docetaxel in Advanced Carcinoma of the Urothelium [NCT00004223] | Phase 2 | 0 participants | Interventional | 2000-02-24 | Completed |
| The Effect of Preoperative Docetaxel, Cisplatin and Capecitabine on Serum RUNX3 Hypermethylation Status in Patients With Gastric and Lower Oesophagus Adenocarcinoma. [NCT00674167] | Phase 2 | 21 participants (Actual) | Interventional | 2007-05-31 | Active, not recruiting |
| Preoperative Chemoradiotherapy In Non-Small Cell Lung Cancer (NSCLC) Patients With Operable Stage IIIB Disease: A Prospective Phase II Trial [NCT00030810] | Phase 2 | 46 participants (Actual) | Interventional | 2001-09-30 | Completed |
| Multicenter Phase III, Randomized Study to Evaluate Treatment Customized According to RAP80 and BRCA1 Assessment in Patients With Advanced Non-small-cell Lung Cancer [NCT00617656] | Phase 3 | 400 participants (Actual) | Interventional | 2008-02-29 | Terminated(stopped due to No safety reasons. Interim analysis shows that the hypothesis superiority of the experimental arm over the control arm- would not be confirmed.) |
| A Phase ll Trial of Induction Docetaxel and S-1 Followed by Concomitant Radiotherapy With Low-dose Daily Cisplatin in Locally Advanced Head and Neck Cancer [NCT00625937] | Phase 2 | 46 participants (Anticipated) | Interventional | 2006-11-30 | Recruiting |
| Nab-paclitaxel Compared With Docetaxel Followed by Anthracyclines and Cyclophosphamide in the Neoadjuvant Breast Cancer [NCT04182568] | Phase 4 | 100 participants (Anticipated) | Interventional | 2019-08-21 | Recruiting |
| Docetaxel-based Chemoradiotherapy Plus Periradiation Chemotherapy in R0 Gastric Cancer [NCT02640898] | | 500 participants (Anticipated) | Interventional | 2015-12-31 | Recruiting |
| Randomized Adjuvant Phase III Trial of Six Cycles of Docetaxel+Hormonal Treatment Versus Hormonal Treatment in Patients With Intermediate or High-risk Prostate Cancer Treated With Radical Radiotherapy [NCT00653848] | Phase 3 | 378 participants (Actual) | Interventional | 2007-05-31 | Active, not recruiting |
| A Phase I Dose Escalation Trial of Once Daily Oral Treatment Using Afatinib (BIBW2992) Plus Gemcitabine or Docetaxel in Patients With Relapsed or Refractory Solid Tumors. [NCT01251653] | | 94 participants (Actual) | Observational | 2010-11-30 | Completed |
| Phase Ⅲ Randomized Trial of Cisplatin Plus Docetaxel Versus Cetuximab, Cisplatin, and Docetaxel Induction Chemotherapy Followed by Concurrent Chemoradiation in Previously Untreated Patients Metastatic Nasopharyngeal Carcinoma [NCT02633176] | Phase 3 | 120 participants (Anticipated) | Interventional | 2015-01-31 | Recruiting |
| A Single-arm, Multicenter, Phase Ⅱ Clinical Study of Docetaxel for Injection (Albumin-bound) in Patients With Pancreatic Cancer Who Have Received at Least One Line of Therapy [NCT05616494] | Phase 2 | 53 participants (Anticipated) | Interventional | 2022-12-06 | Recruiting |
| Biweekly Docetaxel (Taxotere®)in Combination With Capecitabine (Xeloda®)as First-Line Treatment in Patients With Advanced Gastric Cancer [NCT00669370] | Phase 2 | 50 participants (Anticipated) | Interventional | 2006-06-30 | Recruiting |
| Pilot Evaluation of Bevacizumab, in Combination With Docetaxel and Cyclophosphamide in the Adjuvant Treatment of Patients With HER 2 Negative Breast Cancer [NCT00911716] | | 106 participants (Actual) | Interventional | 2008-10-31 | Completed |
| [NCT02627248] | Phase 4 | 200 participants (Anticipated) | Interventional | 2015-10-31 | Recruiting |
| A Phase II Study of Irinotecan (CPT-11) and Docetaxel (Taxotere) in Patients With Recurrent Non-Small Cell Lung Cancer [NCT00003900] | Phase 2 | 48 participants (Actual) | Interventional | 1999-10-31 | Completed |
| ProBio: An Outcome-adaptive and Randomized Multi-arm Biomarker Driven Study in Patients With Metastatic Prostate Cancer [NCT03903835] | Phase 3 | 750 participants (Anticipated) | Interventional | 2019-02-01 | Recruiting |
| A Phase II Study of Bevacizumab Plus Docetaxel and Gemcitabine in Subjects With Advanced, Previously Untreated, Non-Squamous Non-Small Cell Lung Cancer [NCT00970684] | Phase 2 | 13 participants (Actual) | Interventional | 2009-09-30 | Completed |
| A Single-Arm, Phase 2 Study of Ramucirumab in Combination With Weekly Docetaxel in Patients With Stage IV Non-Small Cell Lung Cancer Following Disease Progression After Prior Platinum-Based Chemotherapy [NCT02831491] | Phase 2 | 0 participants (Actual) | Interventional | 2016-11-30 | Withdrawn(stopped due to To pursue broader program objectives in oncology.) |
| Phase II Trial Of Gemcitabine and Docetaxel With Bevacizumab in Selected Sarcoma Subtypes [NCT00887809] | Phase 2 | 47 participants (Actual) | Interventional | 2009-04-30 | Completed |
| [NCT00539630] | Phase 3 | 86 participants (Actual) | Interventional | 2002-11-30 | Completed |
| [NCT00539669] | Phase 2 | 47 participants (Actual) | Interventional | 2003-03-31 | Completed |
| Phase III Multicenter Study of the Effects on Quality of Life of Three-weekly Versus Weekly First-line Chemotherapy for Metastatic or Locally Advanced Breast Cancer [NCT00540800] | Phase 3 | 139 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Induction Chemotherapy of Docetaxel, Cisplatin and Xeloda in Nomogram-predicted High Risk Locoregionally Advanced Nasopharyngeal Carcinoma [NCT02786641] | Phase 3 | 235 participants (Anticipated) | Interventional | 2016-08-31 | Not yet recruiting |
| Randomized Single Institution Pilot Study of Vaccinia-CEA(6D)-TRICOM and Fowlpox-CEA(6D)-TRICOM With GM-CSF in Combination With Docetaxel in Patients With CEA-Bearing Cancers [NCT00088933] | Phase 1 | 60 participants (Actual) | Interventional | 2004-06-30 | Terminated |
| Phase I Trial of Fixed Dose STI571 (Imatinib Mesylate) With Escalating Doses of Docetaxel in Patients With Metastatic Androgen-Independent Prostate Cancer [NCT00038194] | Phase 1 | 28 participants (Actual) | Interventional | 2001-10-31 | Completed |
| Phase II Multicentre Open Label Trial Evaluating the Efficacy and Safety of the Liposomal Doxorubicin (Myocet®) and Docetaxel (Taxotere®) Combination as First-line Treatment of Patients With Metastatic HER2/Neu Negative Breast Cancer [NCT00377559] | Phase 2 | 70 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Adjuvant Chemotherapy in Elderly Patients With Breast Cancer: Weekly Docetaxel vs. CMF [NCT00331097] | Phase 3 | 300 participants (Actual) | Interventional | 2003-07-31 | Completed |
| A Randomized Phase II Study of Concurrent Cisplatin-radiotherapy With or Without Neoadjuvant Chemotherapy Using Taxotere and Cisplatin in Advanced Nasopharyngeal Carcinoma (NPC) [NCT00436293] | Phase 2 | 61 participants (Actual) | Interventional | 2002-12-31 | Completed |
| An Multicenter, Randomized Study of Comparison of Docetaxel Plus Prednisone With Mitoxantrone Plus Prednisone in the Patients With Hormone-refractory (Androgen-independent) Metastatic Prostate Cancer [NCT00436839] | Phase 3 | 228 participants (Actual) | Interventional | 2007-01-31 | Completed |
| High-dose Alkylating Chemotherapy in Oligo-metastatic Breast Cancer Harboring Homologous Recombination Deficiency [NCT01646034] | Phase 3 | 74 participants (Actual) | Interventional | 2014-09-30 | Active, not recruiting |
| Individualized 1st Line Chemotherapy Based on BRCA1 and RRM1 mRNA Expression Levels for Advanced Non-small Cell Lung Cancer [NCT01424709] | Phase 2 | 120 participants (Anticipated) | Interventional | 2010-12-31 | Active, not recruiting |
| Adjuvant Taxotere in Patients With High Risk Prostate Cancer Post Prostatectomy and Radiation [NCT00186420] | Phase 2 | 13 participants (Actual) | Interventional | 2003-07-31 | Completed |
| Phase 2 Study of Nimotuzumab in Combination With TPF for Head and Neck Squamous Cell Carcinoma [NCT01425736] | Phase 2 | 91 participants (Actual) | Interventional | 2009-01-31 | Completed |
| A Phase II Study of Docetaxel With PI-88 in Patients With Advanced Non-Small-Cell Lung Cancer [NCT00103389] | Phase 2 | 98 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Phase IB Study of Gemcitabine, Docetaxel and Bevacizumab in Patients With Soft Tissue Sarcoma [NCT00276055] | Phase 1 | 38 participants (Actual) | Interventional | 2005-11-30 | Completed |
| A Phase 2 Study of Nivolumab in Combination With Either Rucaparib, Docetaxel, or Enzalutamide in Men With Castration-resistant Metastatic Prostate Cancer [NCT03338790] | Phase 2 | 292 participants (Actual) | Interventional | 2017-12-19 | Active, not recruiting |
| A Phase 3, Multicenter, Randomized, Open-label Trial to Compare the Efficacy and Safety of Pembrolizumab (MK-3475) in Combination With Lenvatinib (E7080/MK-7902) Versus Docetaxel in Previously Treated Participants With Metastatic Non-small Cell Lung Cance [NCT03976375] | Phase 3 | 422 participants (Actual) | Interventional | 2019-06-26 | Active, not recruiting |
| A Randomized Trial of Oral Topotecan Versus Docetaxel in Second-Line Treatment of Non-Small Cell Lung Cancer [NCT00193245] | Phase 2 | 80 participants | Interventional | 2000-11-30 | Completed |
| 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 2 | 50 participants | Interventional | 2003-10-31 | Completed |
| A Randomized Phase III Comparison of Weekly Docetaxel Versus Weekly Docetaxel/Gemcitabine in the Treatment of Elderly or Poor Performance Status Patients With Advanced Non-Small Cell Lung Cancer [NCT00193323] | Phase 2 | 346 participants | Interventional | 2001-08-31 | Completed |
| A Phase II Trial of Taxotere, Cisplatin, and Irinotecan in Advanced Esophageal and Gastric Cancer [NCT00165464] | Phase 2 | 54 participants (Actual) | Interventional | 2001-08-31 | Completed |
| A Multi-Institutional Phase II Pilot Trial With Weekly Docetaxel and Herceptin as First or Second Line Therapy for HER2/Neu Overexpressing Metastatic Breast Cancer [NCT00006104] | Phase 2 | 46 participants (Actual) | Interventional | 1998-09-30 | Completed |
| A Randomized, Open-Label, Controlled, Multi-Center Phase III Clinical Study of Camrelizumab Combined With Famitinib Malate Versus Docetaxel in Patients With Advanced Non-Small Cell Lung Cancer Who Progressed on Prior Immune Checkpoint Inhibitor Treatment [NCT05106335] | Phase 3 | 1 participants (Actual) | Interventional | 2022-01-06 | Terminated(stopped due to Sponsor R & D Strategy Adjustment) |
| A Phase II Study of Docetaxel and Vinorelbine in Advanced Non-Small Cell Lung Carcinoma [NCT00006215] | Phase 2 | 0 participants | Interventional | 1999-10-31 | Active, not recruiting |
| A Phase Ii Clinical Study Using Weekly Low-Dose Taxotere® (Docetaxel) With Concurrent Radiotherapy For Localized, Inoperable Carcinoma Of The Uterine Cervix [NCT00178269] | Phase 2 | 0 participants | Interventional | 2005-01-31 | Completed |
| Phase I Trial of Epirubicin and Taxotere in Patients With Metastatic Androgen Independent Prostate Cancer [NCT00096304] | Phase 1 | 36 participants (Anticipated) | Interventional | 2004-06-08 | Terminated(stopped due to Low accrual) |
| Genomic and Proteomic Analysis of Docetaxel and Capecitabine as Primary Chemotherapy for Stage II-III Breast Cancer [NCT00198237] | Phase 2 | 40 participants | Interventional | 2003-03-31 | Completed |
| Randomized Phase 2 Study of 3 Therapeutic Modalities in PS 2/3 Patients With NSCLC Stage IIIB/IV [NCT00198393] | Phase 2 | 126 participants (Actual) | Interventional | 2004-11-30 | Completed |
| An Open-label, Randomised, Phase II Study of Docetaxel in Combination With a Dietary Phytonutrient in First or Second Line Treatment for Patients With HER2 Negative Locally Advanced or Metastatic Breast Cancer, or Loco-regional Recurrence Not Amenable to [NCT00852332] | Phase 2 | 42 participants (Actual) | Interventional | 2009-08-31 | Terminated(stopped due to The trial was stopped for futility in view of the results of the anticipated analysis) |
| A Randomized Phase II Study of Weekly Docetaxel Plus Cisplatin Followed by Gemcitabine Versus Gemcitabine Plus Cisplatin Followed by Weekly Docetaxel in the Treatment of Advanced Non-small Cell Lung Cancer [NCT00173888] | Phase 2 | 15 participants (Actual) | Interventional | 2003-07-31 | Completed |
| Phase II Study of Carboplatin Plus Docetaxel (Taxotere) in Patients With Anaplastic Prostate Carcinoma [NCT00514540] | Phase 2 | 121 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Palbociclib + Letrozole Versus Epirubicin + Cyclophosphamide and Sequential Docetaxel as Neoadjuvant Chemotherapy for Postmenopausal Estrogen Receptor-positive Breast Cancer: a Prospective Randomized Controlled Double-blind Phase IV Trial [NCT04137640] | Phase 4 | 152 participants (Anticipated) | Interventional | 2021-07-19 | Not yet recruiting |
| Open-Label, Cooperative, Randomized, Multicenter Phase III Study on the Use of Cisplatin Resistant Genotype (ERCC1 Over-Expression) in Tumor RNA to Customize Chemotherapy in Stage IV-IIIB (Malignant Pleural Effusion) Non-Small-Cell Lung Cancer Patients [NCT00174629] | Phase 3 | 449 participants (Actual) | Interventional | 2001-06-30 | Completed |
| A Phase 1 Study of PS-341 in Combination With Docetaxel in Patients With Advanced Solid Tumors [NCT00049088] | Phase 1 | 24 participants (Actual) | Interventional | 2002-08-31 | Terminated(stopped due to Administratively complete.) |
| A Phase I Trial of Docetaxel/Prednisone Plus Fractionated 177Lu- J591 Anti-prostate-specific Membrane Antigen Monoclonal Antibody in Patients With Metastatic, Castrate-resistant Prostate Cancer [NCT00916123] | Phase 1 | 15 participants (Actual) | Interventional | 2009-05-31 | Completed |
| Docetaxel (NSC-628503), Cisplatin (NSC-119875), And 5-Fluorouracil (NSC-19893) Induction Chemotherapy Followed By Accelerated Fractionation/Concomitant Boost Radiation And Concurrent Single Agent Cisplatin (NSC-119875), In Patients With Advanced Squamous [NCT00054054] | Phase 2 | 0 participants | Interventional | 2003-04-30 | Completed |
| 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 2 | 14 participants (Actual) | Interventional | 2010-08-31 | Terminated |
| Comparing TP (Docetaxel + Cisplatin) and TAC (Docetaxel + Doxorubicin + Cyclophosphamide) in Neoadjuvant Therapy for Operable Triple Negative Breast Cancer, A Multicenter, Randomized, Phase II Clinical Trial [NCT04664972] | Phase 2 | 212 participants (Actual) | Interventional | 2018-11-23 | Completed |
| A Phase III, Randomized, Multicenter, Open-Label, Two-Arm Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Subcutaneous Administration of the Fixed-Dose Combination of Pertuzumab and Trastuzumab in Combination With Chemotherapy in Chinese P [NCT04024462] | Phase 3 | 200 participants (Actual) | Interventional | 2020-02-05 | Active, 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 2 | 1,200 participants (Anticipated) | Interventional | 2016-11-17 | Recruiting |
| Assessing REsponse to Neoadjuvant Taxotere and Trastuzumab in Nigerian Women With HER2-positive Breast Cancer (ARETTA) [NCT03879577] | Phase 2 | 60 participants (Anticipated) | Interventional | 2019-11-25 | Recruiting |
| Phase II Randomized Adjuvant Trial of Dose-Dense Docetaxel Before or After Doxorubicin/Cyclophosphamide (AC) in Axillary Node-Positive Breast Cancer [NCT00201708] | Phase 2 | 56 participants (Actual) | Interventional | 2004-10-31 | Completed |
| 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 3 | 430 participants (Anticipated) | Interventional | 2023-03-13 | Recruiting |
| A Phase 1/2 Study of BMS-986340 as Monotherapy and in Combination With Nivolumab or Docetaxel in Participants With Advanced Solid Tumors [NCT04895709] | Phase 1/Phase 2 | 665 participants (Anticipated) | Interventional | 2021-05-27 | Recruiting |
| A Phase 2 Study of Magrolimab Combination Therapy in Patients With Head and Neck Squamous Cell Carcinoma [NCT04854499] | Phase 2 | 230 participants (Anticipated) | Interventional | 2021-09-07 | Recruiting |
| Phase II Trial of Gleevec (Imatinib Mesylate) and Taxotere (Docetaxel) as a Combined Regimen for Advanced Gastric Adenocarcinoma [NCT00209079] | Phase 2 | 5 participants (Actual) | Interventional | 2004-09-30 | Terminated(stopped due to Terminated 4/17/07. Drug sponsor withdrew.) |
| Docetaxel by 1 Hour Infusion Followed by 24 Hour Infusion of Cisplatin Plus Capecitabine as Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer [NCT00155259] | Phase 2 | 47 participants (Actual) | Interventional | 2004-10-31 | Completed |
| Phase II Study of Adjuvant Cisplatin and Docetaxel in Non-small Cell Lung Cancer [NCT00582634] | Phase 2 | 4 participants (Actual) | Interventional | 2004-09-30 | Completed |
| Phase IV Randomized Trial of Pemetrexed Followed by Docetaxel or in Reverse Sequence in Non-small-cell Lung Cancer Patients Failed Previous Chemotherapy [NCT01442909] | Phase 4 | 44 participants (Actual) | Interventional | 2008-03-31 | Completed |
| Randomized Study of Docetaxel Versus Docetaxel Plus Genasense™ (G3139; Bcl-2 Antisense Oligonucleotide) in Patients With Previously Treated Non-Small Cell Lung Cancer [NCT00030641] | Phase 2/Phase 3 | 0 participants | Interventional | 2001-10-31 | Active, not recruiting |
| A Multicenter, Randomized Phase II Study Evaluating the Feasibility and Activity of Two Different Combinations of Docetaxel and Gemcitabine and of Cisplatin/Gemcitabine Followed by Docetaxel as First Line Therapy for Locally Advanced Unresectable or Metas [NCT00425191] | Phase 2 | 165 participants (Actual) | Interventional | 2002-07-31 | Completed |
| Clinical Trial of the Neoadjuvant Standard Chemotherapy 3 FEC 100 + 3 TAXOTERE Protocol Versus the Same Protocol Adapted as a Function of Clinical Response [NCT00425516] | Phase 2 | 264 participants (Actual) | Interventional | 2007-01-31 | Completed |
| A Phase 1, Open-Label, Dose-Escalation Trial to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of MGCD0103 (MG-0103) in Combination With Docetaxel (Taxotere®) in Subjects With Advanced Solid Malignancies [NCT00511576] | Phase 1 | 54 participants (Anticipated) | Interventional | 2007-08-31 | Terminated(stopped due to Celgene terminated its collaboration agreement with MethylGene for the development of MGCD0103. All Celgene-sponsored trials with MGCD0103 will be closed.) |
| Evaluation of Primary Chemotherapy With Docetaxel Plus Capecitabine in Selected Patients With Newly Diagnosed Localized or Locally Advanced Prostate Cancer [NCT00151047] | Phase 2 | 15 participants (Actual) | Interventional | 2003-03-31 | Completed |
| A Phase I Study of 17-N-Allylamino-17-Demethoxy Geldanamycin (17-AAG, NSC# 330507) in Combination With Docetaxel in Patients With Advanced Solid Tumors [NCT00058253] | Phase 1 | 80 participants (Actual) | Interventional | 2003-02-28 | Completed |
| A Dose Regimen-Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Activity of Oradoxel Monotherapy in Subjects With Advanced Malignancies [NCT02963168] | Phase 1 | 24 participants (Anticipated) | Interventional | 2017-04-20 | Recruiting |
| A Randomized Phase II Study Comparing Single-Agent Docetaxel to Alternating Docetaxel-Gemcitabine as Primary Chemotherapy in Patients With Metastatic Breast Cancer [NCT00191243] | Phase 2 | 237 participants (Actual) | Interventional | 2002-03-31 | Completed |
| A Phase 1 First In Human Study Evaluating Safety And Efficacy Of ABBV-637 As Either Monotherapy Or In Combination In Adult Subjects With Relapsed And Refractory Solid Tumors [NCT04721015] | Phase 1 | 81 participants (Actual) | Interventional | 2021-02-23 | Active, not recruiting |
| Phase III Study of Docetaxel in Combination With Gemcitabine Versus Docetaxel in Combination With Capecitabine in Patients With Locally Advanced or Metastatic Breast Cancer [NCT00191438] | Phase 3 | 300 participants | Interventional | 2002-10-31 | Completed |
| [NCT01862081] | Phase 1 | 80 participants (Actual) | Interventional | 2013-07-16 | Completed |
| Phase II Study of Gleevec and Taxotere in Recurrent Non-Small Cell Lung Cancer [NCT00222144] | Phase 2 | 23 participants (Actual) | Interventional | 2004-09-30 | Completed |
| Perioperative Immunotherapy vs. Chemo-immunotherapy Stratified by Early Response Evaluation in Patients With Advanced Gastric Cancer (GC) and Adenocarcinoma of the Esophago-gastric Junction (AEG) [NCT04062656] | Phase 2 | 21 participants (Actual) | Interventional | 2019-09-26 | Active, not recruiting |
| PhAse 1/2 StuDy of Modern ImmunotherApy in BCG-Unresponsive, BCG-RelaPsing, and High-Risk BCG-Naive Non-muscle Invasive UroThelial Carcinoma of the BLADDER [NCT03317158] | Phase 1/Phase 2 | 55 participants (Anticipated) | Interventional | 2017-11-21 | Recruiting |
| A Phase II Study of Docetaxel, Oxaliplatin and S-1 (DOS) in Patients With Advanced Gastric Cancer [NCT00525005] | Phase 2 | 44 participants (Actual) | Interventional | 2007-08-31 | Completed |
| Phase II Study of Induction Docetaxel, Cisplatin and 5-Fluorouracil Chemotherapy in Squamous Cell Carcinoma of the Oral Cavity With Molecular Endpoints [NCT00400205] | Phase 2 | 14 participants (Actual) | Interventional | 2006-08-31 | Terminated(stopped due to Safety reasons) |
| A Study to Evaluate Navelbine in Combination With Trastuzumab Plus Pertuzumab in Patients With HER2 Positive Early Stage or Locally Advanced Breast Cancer in Neoadjuvant Treatment [NCT04665986] | Phase 3 | 50 participants (Anticipated) | Interventional | 2021-03-01 | Not yet recruiting |
| A Randomized Study of Cetuximab or Cetuximab Plus Docetaxel Followed by Radical Prostatectomy for Patients With Adenocarcinoma of the Prostate [NCT00448097] | Phase 2 | 7 participants (Actual) | Interventional | 2007-02-28 | Terminated(stopped due to lack of patient population - slow accrual) |
| A Randomized, Open-label Study of the Effect of Adjuvant Therapy With Adriamycin Plus Cytoxan Followed by Taxotere or Taxotere Plus Xeloda on Overall Survival in Female Patients With High-risk Breast Cancer [NCT00089479] | Phase 3 | 2,611 participants (Actual) | Interventional | 2002-08-31 | Completed |
| Pilot Phase IIa Study of Metronomic Chemotherapy With Taxotere (Docetaxel) Plus Nexavar (Sorafenib) as First-Line Therapy in Performance Status-2 Patients With Advanced Non-Squamous Cell Non-Small Cell Lung Cancer [NCT00801801] | Phase 2 | 5 participants (Actual) | Interventional | 2008-01-31 | Terminated(stopped due to Sponsors withdrew funding; preliminary efficacy data was not encouraging.) |
| Anti-HER2 TKI Versus Pertuzumab in Combination With Dose-dense Trastuzumab and Taxane as First Line in HER2-positive Breast Cancer Patients With Active Brain Metastases: A Phase II, Multicenter, Double-blind, Randomized Clinical Trial [NCT04760431] | Phase 2 | 120 participants (Anticipated) | Interventional | 2021-10-01 | Not yet recruiting |
| A Randomized Phase III Comparing Sequential Therapy With TPF/Chemoradiation (ST) To Cisplatinum-Based Chemoradiotherapy [PARADIGM TRIAL] [NCT00095875] | Phase 3 | 145 participants (Actual) | Interventional | 2004-08-31 | Completed |
| A Multi-center Randomized Phase II Study of Doxorubicin Liposome Versus Epirubicin Plus Cyclophosphamide Combined With Trastuzumab and Pertuzumab(HP), Followed by Taxon Plus HP as Neoadjuvant Therapy for HER2-positive Early Breast Cancer [NCT04172259] | Phase 2 | 156 participants (Anticipated) | Interventional | 2019-01-10 | Active, 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 3 | 505 participants (Actual) | Interventional | 2017-03-04 | Active, not recruiting |
| Neoadjuvant Hormonal Therapy Combined With Chemoimmunotherapy (Taxotere, Trastuzumab and Pertuzumab) in Patients With HER2-positive and ER-Positive Breast Cancer (NeoHTTP Study) [NCT02345772] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2014-07-31 | Terminated(stopped due to PI no longer at site. Data was not collected) |
| Phase II Trial of Neoadjuvant Docetaxel and CG1940/CG8711 Followed by Radical Prostatectomy in Patients With High-Risk, Clinically Localized Prostate Cancer [NCT00577356] | Phase 2 | 6 participants (Actual) | Interventional | 2008-02-29 | Terminated(stopped due to Safety reasons, though no safety issues arose.) |
| MITOXANTRONE (N) VS. 5-FLUOROURACIL, EPIRUBICIN AND CYCLOPHOSPHAMIDE AS FIRST-LINE CHEMOTHERAPY FOR PATIENTS WITH METASTATIC BREAST CANCER AND AN UNFAVORABLE PROGNOSIS [NCT00002544] | Phase 3 | 300 participants (Anticipated) | Interventional | 1993-05-31 | Completed |
| Randomized Phase II Study of Docetaxel/Gemcitabine vs. Docetaxel/Cisplatin in Metastatic or Locoregionally Advanced Pancreatic Carcinoma [NCT00004884] | Phase 2 | 96 participants (Actual) | Interventional | 1999-07-31 | Completed |
| A Phase II Double-Blinded, Randomized, Placebo-Controlled Study of Indoximod in Combination With a Taxane Chemotherapy in Metastatic Breast Cancer [NCT01792050] | Phase 2 | 169 participants (Actual) | Interventional | 2013-02-28 | Completed |
| A Study of Raltitrexed Plus Docetaxel Versus Docetaxel as Second-line Chemotherapy in Subjects With Gastric Cancer [NCT01836120] | Phase 2 | 100 participants (Anticipated) | Interventional | 2013-04-30 | Active, not recruiting |
| 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 3 | 567 participants (Anticipated) | Interventional | 2012-07-31 | Recruiting |
| A Multi-Center, Phase 1/1b, Open-Label, Dose Escalation Study of ABT-700, a Monoclonal Antibody in Subjects With Advanced Solid Tumors [NCT01472016] | Phase 1 | 74 participants (Actual) | Interventional | 2011-10-06 | Completed |
| The ELDORADO (Eligard®, Docetaxel and Radiotherapy) Study: A Phase II Study of Chemo - Hormonal Therapy and Radiation in High Risk Prostate Cancer [NCT00452556] | Phase 2 | 86 participants (Anticipated) | Interventional | 2007-05-31 | Active, not recruiting |
| 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) | Observational | 2002-02-28 | Completed |
| A Phase 1/2 Study of Picoplatin and Docetaxel (With Prednisone) in Subjects With Chemotherapy-Naive Metastatic Hormone-Refractory Prostate Cancer [NCT00448734] | Phase 1/Phase 2 | 95 participants (Anticipated) | Interventional | 2006-06-30 | Active, not recruiting |
| A Phase I Study of Intraperitoneal Hyperthermic Docetaxel at the Time of Second Look Surgery Following Front-Line Normothermic Intraperitoneal and Intravenous Cisplatin/Paclitaxel for Patients With Stage II and III Ovarian Carcinoma [NCT00474669] | Phase 1 | 30 participants (Anticipated) | Interventional | 2007-06-30 | Completed |
| Vinorelbine and Gemcitabine Versus Docetaxel and Gemcitabine as First Line Treatment in Patients With Advanced or Metastatic Non Small Cell Lung Cancer (NSCLC). A Prospective , Multicenter, Randomized, Phase III Trial [NCT00441740] | Phase 3 | 419 participants (Actual) | Interventional | 2004-04-30 | Completed |
| A Multicenter Randomized Phase III Study of the Docetaxel and Gemcitabine Combination Versus Monotherapy With Gemcitabine as First-line Treatment in Elderly Patients With Advanced Non-Small-Cell Lung Cancer (NSCLC) [NCT00442026] | Phase 3 | 106 participants (Actual) | Interventional | 2006-12-31 | Terminated(stopped due to Due to poor accrual) |
| A Phase Ib, Multi-Center, Open-Label, Dose Escalation Trial of Intravenous PR-104 Given in Combination With Docetaxel or Gemcitabine in Subjects With Solid Tumors [NCT00459836] | Phase 1 | 42 participants (Actual) | Interventional | 2007-02-28 | Completed |
| Gastrectomy Plus Chemotherapy Versus Chemotherapy Alone for Advanced Gastric Cancer With a Single Non-curable Factor [NCT03001726] | | 228 participants (Anticipated) | Observational | 2017-01-31 | Enrolling by invitation |
| Open-label, Phase 1 Trial to Evaluate the Safety and Pharmacokinetic Parameters of a 2-day Pulse of Intravenous (IV) AC480 (AC480IV) Administered as Monotherapy and in Combination With Docetaxel in Patients With Advanced Solid Tumors [NCT01245543] | Phase 1 | 0 participants (Actual) | Interventional | 2010-11-30 | Withdrawn(stopped due to Clinical investigations have been discontinued and transfer to BMS 3/24/2015) |
| A Randomized, Open Label, Parallel Group, Regional, Multicenter, Phase III Study of Oral Gefitinib (IRESSA®) Versus Intravenous Docetaxel (TAXOTERE®) in Patients With Locally Advanced or Metastatic Recurrent Non Small Cell Lung Cancer Who Have Previously [NCT00478049] | Phase 3 | 163 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Phase II Evaluation of Docetaxel and Gemcitabine Plus G-CSF in the Treatment of Recurrent or Persistent Leiomyosarcoma of the Uterus [NCT00031629] | Phase 2 | 51 participants (Actual) | Interventional | 2005-01-31 | Completed |
| 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 2 | 7 participants (Actual) | Interventional | 2007-05-31 | Completed |
| An Open Label, Multi-cohort, Multicenter Phase II Study to Evaluate the Efficacy and Safety of Envofolimab in Combination With BD0801 Injection With/Without Chemotherapy in Patients With Advanced Solid Tumors [NCT05148195] | Phase 2 | 110 participants (Anticipated) | Interventional | 2021-12-22 | Recruiting |
| A Phase 2, Open-label, Randomized, Multi-arm Study of BGB-A445 in Combination With Investigational Agents in Non-Small Cell Lung Cancer Patients Previously Treated With Anti-PD-(L)1 Antibody [NCT06029127] | Phase 2 | 100 participants (Anticipated) | Interventional | 2023-10-23 | Recruiting |
| A Co-clinical Trial in Triple Negative Breast Cancer Patients With Genoproteomic Discovery [NCT02124902] | Phase 2 | 148 participants (Actual) | Interventional | 2014-07-07 | Terminated(stopped due to Insufficient funding/staff) |
| Immunomodulation of Pembrolizumab Plus Docetaxel for the Treatment of Recurrent or Metastatic (R/M) Squamous Cell Carcinoma of the Head and Neck (HNSCC) After Platinum Failure [NCT02718820] | Phase 1/Phase 2 | 22 participants (Actual) | Interventional | 2016-03-31 | Completed |
| Phase II Trial of First Line Docetaxel and Oxaliplatin in Stage IV or Relapsed Non-Small Cell Lung Cancer [NCT01243775] | Phase 2 | 33 participants (Actual) | Interventional | 2010-11-30 | Completed |
| Phase II Trial of Bexarotene (Targretin) Capsules With Tretinoin and Chemotherapy in Patients With Advanced Non-small-cell Lung Cancer [NCT00514293] | Phase 2 | 39 participants (Anticipated) | Interventional | 2007-01-31 | Recruiting |
| Open Label, Randomized Multicentric Phase II Clinical Trial of Mycobacterium w in Combination With Docetaxel Versus Docetaxel in Metastatic Hormone Refractory Prostate Cancer. [NCT00525408] | Phase 2 | 134 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to Interim Analysis report indicates trial futility) |
| Randomised Phase II Screening Study to be Used in an TP/TPF-chemotherapy (Short Induction) Before TP/TPF-induction, Radiotherapy With or Without Cetuximab in the Primary Therapy of the Only by Laryngectomy Operable Carcinoma of the Larynx/Hypopharynx [NCT00508664] | Phase 2 | 180 participants (Actual) | Interventional | 2007-07-31 | Completed |
| Marched Pair Study of the Standard Chemotherapy 4doxorubicin Plus Cyclophosphamide(AC) 60 + 4 Docetaxel Protocol Versus 4 PLD C35+4 Docetaxel in Neoadjuvant Chemotherapy of Breast Cancer [NCT02953184] | Phase 2 | 160 participants (Anticipated) | Interventional | 2016-11-30 | Recruiting |
| Dendritic Cell Vaccination in Combination With Docetaxel for Patients With Cancer Prostate - a Randomized Phase II Study [NCT01446731] | Phase 2 | 43 participants (Actual) | Interventional | 2011-10-31 | Completed |
| Phase I Study Panitumumab Plus Chemoradiotherapy and Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Cancer of the Head and Neck [NCT00513383] | Phase 1 | 34 participants (Actual) | Interventional | 2006-04-30 | Completed |
| [NCT02940990] | Phase 2 | 50 participants (Anticipated) | Interventional | 2016-11-30 | Not yet recruiting |
| p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer: A Multicenter, Randomized Controlled, Predictive Marker Clinical Trial [NCT00525200] | Phase 3 | 170 participants (Actual) | Interventional | 2007-06-30 | Completed |
| S1 Plus Docetaxel Versus Capecitabine Plus Docetaxel First-line Treatment in Patients With Advanced Breast Cancer: a Phase 2, Prospective,Multicenter, Randomised Study [NCT02947061] | Phase 2 | 300 participants (Anticipated) | Interventional | 2015-04-30 | Recruiting |
| Veterans Affairs Seamless Phase II/III Randomized Trial of STAndard Systemic theRapy With or Without PET-directed Local Therapy for OligoRecurrenT Prostate Cancer (VA STARPORT) [NCT04787744] | Phase 2/Phase 3 | 464 participants (Anticipated) | Interventional | 2021-07-01 | Recruiting |
| A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating the Efficacy and Safety of AB928-Based Treatment Combinations in Patients With Metastatic Castrate Resistant Prostate Cancer [NCT04381832] | Phase 1/Phase 2 | 173 participants (Actual) | Interventional | 2020-07-07 | Active, 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 3 | 452 participants (Anticipated) | Interventional | 2019-11-05 | Active, not recruiting |
| Tocotrienol in Combination With Neoadjuvant Chemotherapy for Women With Breast Cancer [NCT02909751] | Phase 2 | 80 participants (Actual) | Interventional | 2016-09-14 | Completed |
| [NCT00086268] | Phase 3 | 250 participants (Actual) | Interventional | 2004-04-30 | Completed |
| Concurrent Chemotherapy Based on Genetic Testing in Patients With High-Risk Salivary Gland Tumors [NCT02921984] | Phase 1 | 20 participants (Actual) | Interventional | 2013-09-30 | Completed |
| Phase I/II Trial of Samarium Sm-153 Lexidronam Combined With Docetaxel for Patients With Androgen-Independent Prostate Cancer [NCT00121095] | Phase 1/Phase 2 | 69 participants (Anticipated) | Interventional | 2005-07-31 | Recruiting |
| 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 3 | 400 participants (Anticipated) | Interventional | 2008-01-31 | Active, not recruiting |
| Phase III Randomized Study Of Adjuvant Hormonal Therapy With And Without Docetaxel And Estramustine In Patients With Advanced Prostate Cancer Or With A High Risk Of Relapse [NCT00055731] | Phase 3 | 413 participants (Actual) | Interventional | 2002-11-14 | Completed |
| Ph1 Study of the Safety, PK, and PDn of Escalating Oral Doses of the Glutaminase Inhibitor CB-839, as a Single Agent and in Combination With Standard Chemotherapy in Patients With Advanced and/or Treatment-Refractory Solid Tumors [NCT02071862] | Phase 1 | 210 participants (Actual) | Interventional | 2014-02-28 | Completed |
| Predictive fActors for toleraNce to Taxane Based CHemotherapy In Older adultS Affected by mEtastatic Prostate Cancer, a Prospective Observational Study (ANCHISES) [NCT05471427] | | 118 participants (Actual) | Observational | 2020-01-01 | Completed |
| Phase II Study to Determine the Effects of Neoadjuvant Docetaxel on Newly Diagnosed Intermediate and High Grade Cancer of the Prostate in Patients Who Are Scheduled for Radical Prostatectomy With Genomic Correlates of Pathological Response [NCT00598858] | Phase 2 | 0 participants (Actual) | Interventional | 2009-01-31 | Withdrawn(stopped due to Halted due to zero accrual and lack of funding) |
| A Phase I Study of the PI3-Kinase Inhibitor BKM120 in Combination With Docetaxel in Patients With Advanced Solid Tumors. [NCT01540253] | Phase 1 | 38 participants (Actual) | Interventional | 2012-05-31 | Completed |
| Phase II Trial of Neoadjuvant[FEC100]/Cisplatin-Docetaxel ± Trastuzumab in Women With Over Expressed or Amplified Her2/Neu With Locally Advanced Breast Cancer [NCT00535509] | | 285 participants (Actual) | Interventional | 2007-06-30 | Completed |
| 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 2 | 100 participants (Anticipated) | Interventional | 2003-03-31 | Recruiting |
| A Randomized, Phase 2 Study of INCB039110 or Placebo in Combination With Docetaxel in Subjects With Previously Treated Stage IIIb, IV, or Recurrent Non-Small Cell Lung Cancer [NCT02257619] | Phase 2 | 9 participants (Actual) | Interventional | 2014-09-30 | Terminated(stopped due to Sponsor decision to not initiate part 2 due to slow enrollment and competing trials.) |
| Phase II Trial Assessing the Impact on Instrumental and Daily Living Autonomy of a Chemotherapy With Biweekly Docetaxel in the Treatment of Metastatic Breast Cancer in Patients Over 70 [NCT00104624] | Phase 2 | 53 participants (Anticipated) | Interventional | 2005-05-31 | Terminated(stopped due to Toxicity issues) |
| 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) | Interventional | 2009-07-31 | Completed |
| Randomized Phase Ii Trial Of Weekly Docetaxel, Estramustine And Prednisone Versus Docetaxel And Prednisone In Patient With Hormone-Resistant Prostate Cancer [NCT00541281] | Phase 2 | 150 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Study of GSK2302024A Antigen-Specific Cancer Immunotherapeutic Combined With Standard Neoadjuvant Treatment in Patients With WT1-positive Primary Invasive Breast Cancer [NCT01220128] | Phase 2 | 66 participants (Actual) | Interventional | 2011-04-11 | Terminated(stopped due to Study termination due to negative Ph III of another study product from same technology platform.) |
| Study of Chinese Medicine Plus Chemotherapy Maintenance Versus Chemotherapy Maintenance in Advanced Non Small Cell Lung Cancer: A Randomized Double-blind Controlled Clinical Trial [NCT02900742] | Phase 3 | 71 participants (Actual) | Interventional | 2013-03-31 | Completed |
| Phase II Study of Patients With Hormone-Naïve Prostate Cancer With a Rising Prostate Specific Antigen: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), Thalidomide Plus Docetaxel [NCT00450008] | Phase 2 | 9 participants (Actual) | Interventional | 2006-12-31 | Terminated(stopped due to PI decision) |
| An Open-label, Randomized Phase IIB/III Active Control Study of Second-line Tergenpumatucel-L (Hyper-Acute(R)-Lung ) Immunotherapy Versus Docetaxel in Progressive or Relapsed Non-Small Cell Lung Cancer [NCT01774578] | Phase 2/Phase 3 | 135 participants (Actual) | Interventional | 2013-02-28 | Terminated |
| A Phase 1 Study of AG-270 in the Treatment of Subjects With Advanced Solid Tumors or Lymphoma With Homozygous Deletion of MTAP [NCT03435250] | Phase 1 | 123 participants (Actual) | Interventional | 2018-03-04 | Terminated(stopped due to Strategic reasons) |
| A Phase 2 Study of the Safety and Efficacy of BIO-11006 in the Treatment of Recurrent Osteosarcoma and Ewing's Sarcoma in Patients With Lung Metastases [NCT04183062] | Phase 2 | 10 participants (Anticipated) | Interventional | 2019-10-04 | Active, not recruiting |
| A Phase 2 Study of Sequential and Concurrent Chemoradiation for Patients With Advanced Nasopharyngeal Carcinoma (NPC) [NCT00896181] | Phase 2 | 26 participants (Actual) | Interventional | 2008-12-10 | Completed |
| A Phase II Study of Biweekly Induction Regimen With Docetaxel, Cisplatin and Fluorouracil for Patients With Locally Advanced Squamous Cell Carcinoma of Head and Neck [NCT04397341] | Phase 2 | 58 participants (Actual) | Interventional | 2014-03-01 | Completed |
| Phase I Study to Evaluate the Maximum Tolerated Dose of the Combination of SH003 and Docetaxel in Patients With Solid Cancer [NCT04360317] | Phase 1 | 9 participants (Anticipated) | Interventional | 2020-06-30 | Not yet recruiting |
| RAnDomized Trial of SPI-2012 Versus Pegfilgrastim in the Management of Chemotherapy Induced Neutropenia in Breast CANCEr Patients Receiving Docetaxel and Cyclophosphamide (TC) (ADVANCE) [NCT02643420] | Phase 3 | 406 participants (Actual) | Interventional | 2016-01-19 | Completed |
| A Study of Nivolumab +/- Docetaxel in Patients Previously Treated With Advanced or Metastatic Non Small Cell Lung Cancer [NCT04023617] | Phase 2 | 72 participants (Anticipated) | Interventional | 2019-07-08 | Recruiting |
| A Phase II Study of OSI-774 in Combination With Cisplatin and Docetaxel in Metastatic or Recurrent Head and Neck Squamous Cell Cancer [NCT00076310] | Phase 2 | 50 participants (Actual) | Interventional | 2004-01-28 | Active, not recruiting |
| A Phase II Study of Imatinib and Docetaxel in Metastatic Hormone Refractory Prostate Cancer [NCT00251225] | Phase 2 | 49 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Phase II Evaluation of Docetaxel Combined With Estramustine Phosphate in Patients With Metastatic Breast Cancer [NCT00003066] | Phase 2 | 40 participants (Anticipated) | Interventional | 1997-02-28 | Active, not recruiting |
| Randomized Phase II Study of Docetaxel and Gemcitabine for Stage IIIB/IV Non-Small Cell Lung Cancer [NCT00003762] | Phase 2 | 106 participants (Actual) | Interventional | 1999-02-28 | Completed |
| A Randomized Phase III Multicenter Trial of Neoadjuvant Docetaxel (Taxotere) Plus Cisplatin Plus 5-Fluorouracil Versus Neoadjuvant Cisplatin Plus 5-Fluorouracil in Patients With Locally Advanced Inoperable Squamous Cell Carcinoma of the Head and Neck [NCT00003888] | Phase 3 | 359 participants (Actual) | Interventional | 1999-04-30 | Completed |
| A Phase II Trial of Docetaxel, Cisplatin, 5-FU, and Leucovorin for Carcinoma of the Nasopharnyx [NCT00004164] | Phase 2 | 0 participants | Interventional | 1999-08-31 | Active, not recruiting |
| SHERLOC: A Phase 2 Study of MM-121 in Combination With Docetaxel Versus Docetaxel Alone in Patients With Heregulin Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer (Merrimack Pharmaceuticals Inc.) [NCT02387216] | Phase 2 | 153 participants (Actual) | Interventional | 2015-02-01 | Terminated(stopped due to Based on the preliminary results seen during interim analysis, which were confirmed in the final analysis, the Sponsor terminated the study) |
| Pilot Study to Evaluate the Effect of Intrapleural Docetaxel Administration Using Medical Pleuroscopy in Malignant Effusion With Lung Cancer [NCT03394105] | Phase 2 | 4 participants (Actual) | Interventional | 2016-07-26 | Completed |
| ZD-1839 (Iressa®) With Concurrent Docetaxel and Conformal Three Dimensional Thoracic Radiation Followed by Consolidative Docetaxel and ZD-1839 for Patients With Stage III Non Small Cell Lung Cancer: A Phase I Study [NCT00310154] | Phase 1 | 45 participants (Anticipated) | Interventional | 2003-11-30 | Completed |
| A Multi-center Phase II Randomized Study of Customized Neoadjuvant Therapy Versus Standard Chemotherapy in Non-small Cell Lung Cancer (NSLC) Patients With Resectable Stage IIIA (N2) Disease (CONTEST-TRIAL) [NCT01784549] | Phase 2 | 168 participants (Anticipated) | Interventional | 2012-07-31 | Recruiting |
| Phase II Study of Docetaxel and Gemcitabine in Previously Treated Metastatic Esophageal Squamous Cell Cancer [NCT01469598] | Phase 2 | 24 participants (Actual) | Interventional | 2011-08-31 | Completed |
| A Phase II Study of Neoadjuvant Chemotherapy With Docetaxel, Capecitabine, Cisplatin, and Bevacizumab in Patients With Unresectable Advanced Gastric Cancer [NCT01471470] | Phase 2 | 31 participants (Actual) | Interventional | 2010-07-31 | Completed |
| Multicenter, Explorative Phase II Study of Perioperative 5-FU, Leucovorin, Docetaxel, and Oxaliplatin (FLOT) in Combination With Trastuzumab in Patients With HER2-positive, Locally Advanced, Resectable Adenocarcinoma of the Gastroesophageal Junction or St [NCT01472029] | Phase 2 | 53 participants (Actual) | Interventional | 2011-12-31 | Completed |
| Metformin With Standard Taxotere and Prednisone in the Treatment of Castration Resistant Prostate Cancer [NCT01478308] | Phase 2 | 0 participants (Actual) | Interventional | 2011-06-30 | Withdrawn(stopped due to No accrual in initial period, PI decided to close study.) |
| Randomized Phase II Trial of Two Different Schedules of Docetaxel Plus Cisplatin as First-Line Therapy in Advanced Non-Small Cell Lung Cancer [NCT00319514] | Phase 2 | 78 participants | Interventional | 2004-04-30 | Completed |
| 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 2 | 120 participants (Anticipated) | Interventional | 2010-10-31 | Completed |
| Phase II Study of Docetaxel and Epirubicine as First-Line Treatment in Patients With Advanced or Metastatic Adenocarcinoma of the Stomach [NCT00075465] | Phase 2 | 0 participants | Interventional | 2001-04-30 | Active, not recruiting |
| Phase I-II Study Of Docetaxel And Oxaliplatine In Patients With Stage III-IV Ovarian Epithelial Cancer [NCT00075543] | Phase 1/Phase 2 | 0 participants | Interventional | 2003-07-31 | Active, not recruiting |
| 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 1 | 18 participants (Anticipated) | Interventional | 2004-09-30 | Completed |
| Randomized Phase II Trial of Sequential Docetaxel Followed by Capecitabine Versus Concomitant Docetaxel/Capecitabine as in Induction Therapy for Early Stage Breast Cancer [NCT00415285] | Phase 2 | 100 participants | Interventional | 2006-12-31 | Recruiting |
| Randomized Phase III Trial Comparing an Association of Hormonal Treatment and Docetaxel Versus the Hormonal Treatment Alone in Metastatic Prostate Cancers [NCT00104715] | Phase 3 | 385 participants (Actual) | Interventional | 2004-10-18 | Completed |
| A Phase II Evaluation of Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF in the Treatment of Recurrent or Advanced Leiomyosarcoma of the Uterus [NCT00101127] | Phase 2 | 0 participants | Interventional | 2003-12-31 | Completed |
| Safety and Pharmacokinetic Study of Jin Fu Kang In Combination With Docetaxel for Patients With Previously Treated Non-Small Cell Lung Cancer [NCT00260026] | Phase 2 | 20 participants | Interventional | 2004-11-30 | Completed |
| Study of Oxaliplatin and Taxotere in Androgen Independent Prostate Cancer [NCT00260611] | Phase 2 | 34 participants (Actual) | Interventional | 2004-11-30 | Completed |
| Randomized Phase III Trial Comparing Induction Chemotherapy With Cisplatin/5-fluorouracil (PF) or Docetaxel/Cisplatin/5-fluorouracil (TPF) Plus Chemoradiotherapy (CRT) Versus CRT Alone as First-line Treatment or Unresectable Locally Advanced Head and Neck [NCT00261703] | Phase 2/Phase 3 | 439 participants (Actual) | Interventional | 2002-12-31 | Completed |
| A Randomized Trial of Pivanex Plus Docetaxel or Docetaxel Monotherapy in Patients With Chemotherapy Resistant Advanced Non-Small Cell Carcinoma of the Lung (NSCLC) [NCT00073385] | Phase 2 | 225 participants | Interventional | 2003-09-30 | Completed |
| Phase I/II Study of Neoadjuvant Weekly Docetaxel and Mitoxantrone Prior to Prostatectomy in Patients With High Risk Localized Prostate Cancer [NCT00017563] | Phase 2 | 57 participants (Actual) | Interventional | 2000-09-30 | Completed |
| A Phase III Trial of Standard Fractionation Radiation and Concurrent Single Agent Cisplatin, With and Without Docetaxel, Cisplatin, and 5-Fluorouracil Induction Chemotherapy, in Patients With Advanced Oropharyngeal Squamous Cell Cancer [NCT00268372] | Phase 3 | 6 participants (Actual) | Interventional | 2005-12-31 | Terminated(stopped due to SWOG eliminated its head and neck committee) |
| National Trial Phase II to Study the Combination of Gemcitabine and Docetaxel in Patients With Locally Advanced or Metastatic Pancreatic or Biliary Adenocarcinoma That Cannot be Removed by Surgery [NCT00268840] | Phase 2 | 45 participants (Actual) | Interventional | 2001-08-31 | Completed |
| A Phase I Trial of Docetaxel and PTK787 in Metastatic Breast Cancer Patients and Recurrent or Refractory Gynecological Cancer Patients [NCT00268918] | Phase 1 | 24 participants (Actual) | Interventional | 2005-09-30 | Completed |
| 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 3 | 17 participants (Actual) | Interventional | 2003-10-31 | Completed |
| A Phase II Study of Taxotere (Docetaxel) Plus Adriamycin (Doxorubicin) and Prednisone (TAP) in Hormone-Refractory Prostate Cancer [NCT00416533] | Phase 2 | 47 participants (Anticipated) | Interventional | 2004-08-31 | Completed |
| A Multicenter, Randomized Phase II Study of Two Schedules of Taxotere (Weekly Versus Every 3 Weeks) in Elderly or Poor Performance (ECOG PS 2), Chemotherapy-Naive Patients With Advanced Non-Small Cell Lung Cancer [NCT00075374] | Phase 2 | 6 participants (Actual) | Interventional | 2003-10-31 | Completed |
| A Randomized, Open-Label, Parallel Group, International, Multicenter, Phase III Study of Oral ZD1839 (IRESSA®) Versus Intravenous Docetaxel (TAXOTERE®) in Patients With Locally Advanced or Metastatic Recurrent Non-Small Cell Lung Cancer Who Have Previousl [NCT00076388] | Phase 3 | 1,440 participants | Interventional | 2004-02-29 | Completed |
| 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 2 | 46 participants (Actual) | Interventional | 2005-04-30 | Terminated(stopped due to Investigator abruptly left Carilion.) |
| Phase II Trial of Weekly Irinotecan and Docetaxel in Refractory Metastatic Breast Cancer [NCT00079118] | Phase 2 | 70 participants (Actual) | Interventional | 2004-04-30 | Completed |
| [NCT01660542] | Phase 4 | 96 participants (Actual) | Interventional | 2011-04-30 | Completed |
| Randomized Double-Blind Phase II Trial of Docetaxel and Imatinib Versus Docetaxel and Placebo in Metastatic Androgen-Independent Prostate Cancer (AIPC) With Bone Metastases [NCT00080678] | Phase 2 | 116 participants (Actual) | Interventional | 2003-05-31 | Completed |
| A Phase II Study of GTI-2040 in Combination With Docetaxel and Prednisone in Hormone-Refractory Prostate Cancer [NCT00087165] | Phase 2 | 22 participants (Actual) | Interventional | 2005-01-31 | Completed |
| Phase I/II Study of Inhaled Doxorubicin Plus IV Docetaxel and Cisplatin in Patients With Locally Advanced or Metastatic Unresectable Non Small Cell Lung Cancer [NCT00082472] | Phase 1/Phase 2 | 30 participants | Interventional | 2004-01-31 | Active, not recruiting |
| A Randomized Phase III Study Comparing Epirubicin, Docetaxel and Capecitabine + G-CSF to Epirubicin and Docetaxel + G-CSF as Neoadjuvant Treatment for Early HER-2 Negative Breast Cancer and Comparing Epirubicin, Docetaxel and Capecitabine + G-CSF ± Trastu [NCT00309556] | Phase 3 | 536 participants (Actual) | Interventional | 2005-02-28 | Completed |
| Phase II Trial Of Docetaxel With Capecitabine And Bevacizumab As First-Line Chemotherapy For Patients With Metastatic Breast Cancer [NCT00088998] | Phase 2 | 46 participants (Actual) | Interventional | 2004-12-31 | Completed |
| 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 2 | 1 participants (Actual) | Interventional | 2005-12-31 | Terminated(stopped due to Terminated due to low subject accrual) |
| A Phase I/II Study of Docetaxel/Prednisone and PTK 787/ZK 222584 in Previously Untreated Metastatic Hormone Refractory Prostate Cancer [NCT00293371] | Phase 1/Phase 2 | 6 participants (Actual) | Interventional | 2005-02-28 | Terminated(stopped due to low accrual) |
| A Randomized Phase III Study Comparing Concomitant Docetaxel Plus Gemcitabine to Sequential Therapy of Docetaxel Followed by Gemcitabine in Anthracycline-Pretreated Metastatic or Locally Recurrent Breast Cancer Patients [NCT00294385] | Phase 3 | 430 participants (Actual) | Interventional | 2002-06-30 | Completed |
| A Phase III Randomized, Open-Label Study of CG1940 and CG8711 Versus Docetaxel and Prednisone in Patients With Metastatic Hormone-Refractory Prostate Cancer Who Are Chemotherapy-Naïve [NCT00089856] | Phase 3 | 626 participants (Actual) | Interventional | 2004-07-31 | Terminated(stopped due to Based on futility analysis showing <30% chance of meeting primary endpoint.) |
| Pyrotinib as Neoadjuvant Agent for Non-objective Response Patients of HER2-positive Early Breast Cancer Treated by Trastuzumab, Pertuzumab, and Chemotherapy (PYHOPE-BC-104): a Randomized, Controlled, Phase Ⅱ Trial [NCT04717531] | Phase 2 | 60 participants (Anticipated) | Interventional | 2021-06-03 | Recruiting |
| Multiple-Arm Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of XmAb20717 in Combination With Standard of Care Treatment in Patients With Metastatic Castration Sensitive Prostate Cancer [NCT05733351] | Phase 1 | 30 participants (Anticipated) | Interventional | 2023-08-03 | Recruiting |
| Effectiveness of RaproCell in Alleviating the Side Effects of Chemotherapeutic Agents, Without Adversely Impacting the Overall Success of the Agents on Cancer Cells. [NCT05137067] | Phase 2 | 90 participants (Actual) | Interventional | 2021-01-20 | Completed |
| 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 2 | 70 participants (Actual) | Interventional | 2019-04-02 | Completed |
| A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Canakinumab in Combination With Docetaxel Versus Placebo in Combination With Docetaxel in Adult Subjects With Non-small Cell Lung Cancer (NSCLC) Previous [NCT03626545] | Phase 3 | 245 participants (Actual) | Interventional | 2019-01-23 | Terminated(stopped due to The study was early terminated due to the lack of efficacy of study treatment observed in the analysis of the primary endpoint of the randomized part) |
| A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ramucirumab Plus Docetaxel Versus Placebo Plus Docetaxel in Patients With Locally Advanced or Unresectable or Metastatic Urothelial Carcinoma Who Progressed on or After Platinum-Based Therap [NCT02426125] | Phase 3 | 530 participants (Actual) | Interventional | 2015-07-13 | Completed |
| A Phase I Study of ZD4054 (Zibotentan) in Combination With Docetaxel in 2 Parts, an Open-Label, Non-Randomized, Dose-Finding Part and a Double-Blind, Placebo-Controlled, Randomized Dose Expansion Part, in Patients With Metastatic Hormone-Refractory Prosta [NCT00314782] | Phase 1 | 44 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Phase I/II Study of Neoadjuvant Bortezomib in Combination With Docetaxel and Cisplatin Followed by Surgery in Early Stage Non-Small Cell Lung Cancer. [NCT00313690] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2006-04-30 | Withdrawn(stopped due to Recruitment difficulties) |
| Sequential vs Upfront Intensified Neoadjuvant Chemotherapy in Patients With Large Resectable and/or Locally Advanced Breast Cancer. The INTENS Study [NCT00314977] | Phase 3 | 200 participants (Anticipated) | Interventional | 2006-02-28 | Completed |
| Weekly Docetaxel and Carboplatin in Patients With Recurrent Squamous Carcinoma of the Cervix: A Phase I/II Study [NCT00084890] | Phase 1 | 15 participants (Actual) | Interventional | 2003-11-30 | Terminated(stopped due to slow accrual) |
| A Randomised Phase II Study: Treatment With Daily p.o. Iressa™ (ZD1839) or Placebo in Combination With Weekly IV Infusion of Docetaxel in Patients With Metastatic Breast Cancer [NCT00319618] | Phase 2 | 66 participants | Interventional | 2003-06-30 | Completed |
| A Phase II Study Using FDG-PET to Investigate the Dosing Schedule and Response of Combination SGN-15 (cBR96-Doxorubicin Immunoconjugate) and Docetaxel in Patients With Stage IV or Stage IIIB Non-Small Cell Lung Carcinoma Ineligible for Combined Modality T [NCT00086333] | Phase 2 | 30 participants | Interventional | 2004-07-31 | Completed |
| Phase II Trial Of TAXOTERE + TARCEVA™ To Treat HRPC In Men ≥ 65 Years Of Age [NCT00087035] | Phase 2 | 1 participants (Actual) | Interventional | 2004-05-31 | Completed |
| A Phase Ib/II Clinical Trial of AK112 and AK104 With or Without Chemotherapy in Advanced Non-small Cell Lung Cancer [NCT05904379] | Phase 1/Phase 2 | 148 participants (Anticipated) | Interventional | 2023-07-13 | Recruiting |
| Phase II, Randomized, Open-label, International, Multicenter Study to Compare Efficacy of Standard Chemotherapy vs. Letrozole Plus Abemaciclib as Neoadjuvant Therapy in HR-positive/HER2-negative High/Intermediate Risk Breast Cancer Patients [NCT04293393] | Phase 2 | 200 participants (Actual) | Interventional | 2020-10-02 | Active, not recruiting |
| Phase I Trial of Concurrent Taxotere With Radiation Therapy and Hormonal Therapy For Clinically Localized High Risk Prostate Cancer [NCT00099086] | Phase 1 | 20 participants (Actual) | Interventional | 2007-01-16 | Active, not recruiting |
| A Multicenter Randomized Comparative Study of Docetaxel Plus Epirubicin Versus Docetaxel Plus Capecitabine Combinations as First Line Treatment of Metastatic Breast Cancer [NCT00429871] | Phase 3 | 272 participants (Actual) | Interventional | 2002-05-31 | Completed |
| 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 3 | 377 participants (Actual) | Interventional | 2013-01-24 | Completed |
| 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 3 | 135 participants (Actual) | Interventional | 2004-07-31 | Completed |
| A Multicenter Randomized Study Comparing the Dose Dense, G-CSF-Supported Sequential Administration of FE75C Followed by Docetaxel Versus Paclitaxel as Adjuvant Chemotherapy in Women With Axillary Lymph Node Positive Breast Cancer [NCT00431080] | Phase 3 | 478 participants (Actual) | Interventional | 2004-08-31 | Completed |
| Randomized Phase II Study of the Induction Chemotherapy With Docetaxel Alone vs CDDP + Docetaxel for C-stage IB-II Non-Small Cell Lung Cancer (JCOG 0204-MF) [NCT00132639] | Phase 2 | 80 participants (Actual) | Interventional | 2002-10-31 | Completed |
| A Phase III Randomized, Open-Label Study of Docetaxel in Combination With CG1940 and CG8711 Versus Docetaxel and Prednisone in Taxane-Naïve Patients With Metastatic Hormone-Refractory Prostate Cancer With Pain [NCT00133224] | Phase 3 | 408 participants (Actual) | Interventional | 2005-07-31 | Terminated(stopped due to Accrual and treatment with CG1940/CG8711 stopped due to IDMC recommendation.) |
| A Phase II Study of Docetaxel Plus Carboplatin in Hormone Refractory Prostate Cancer Patients Refractory to Prior Docetaxel-based Chemotherapy [NCT00134706] | Phase 2 | 30 participants (Actual) | Interventional | 2004-01-31 | Completed |
| Randomized Phase II Study Evaluating The Tolerability Of Adjuvant Docetaxel-based Chemotherapy For Completely Resected Stage IB-II Non-Small Cell Lung Cancer (NSCLC): Toledo Trial [NCT00434668] | Phase 2 | 99 participants (Anticipated) | Interventional | 2005-12-31 | Completed |
| Phase I Trial of Weekly Docetaxel and Daily Temozolomide in Patients With Metastatic Disease [NCT00401180] | Phase 1 | 25 participants (Actual) | Interventional | 2002-06-30 | Completed |
| Phase II Trial of Docetaxel and Carboplatin Administered Every Two Weeks as Induction Therapy for Stage II or III Breast Cancer [NCT00107510] | Phase 2 | 58 participants (Anticipated) | Interventional | 2005-08-31 | Completed |
| A Multicenter Randomized Phase II Study of Docetaxel Versus Vinorelbine as First-Line Treatment in Elderly Patients With Advanced Non-Small-Cell Lung Cancer (NSCLC) [NCT00441922] | Phase 3 | 166 participants (Anticipated) | Interventional | 2003-01-31 | Completed |
| A Phase I/II Study of Docetaxel as a Radiosensitizer for Locally Advanced Cervical Cancer (GIA 13026) [NCT00452920] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2003-09-30 | Withdrawn |
| Phase II Study of Docetaxel and Thalidomide as a Second-Line Treatment for Non-Small Cell Lung Cancer [NCT00114192] | Phase 2 | 37 participants (Anticipated) | Interventional | 2004-06-30 | Completed |
| Randomized Phase II Trial Evaluating [Radiotherapy-Docetaxel-5 Fluorouracil] Association Versus [Radiotherapy-Docetaxel-Cisplatin] Association in Non Resecables First Line of Chemotherapy in Metastatics Pancreas Cancers Patients [NCT00112697] | Phase 2 | 71 participants (Actual) | Interventional | 2003-10-06 | Completed |
| A Randomized Phase III Study Comparing Docetaxel Followed by Cyclophosphamide, Epirubicin and 5-FU to Docetaxel With Capecitabine Followed by Cyclophosphamide, Epirubicin and Capecitabine as Adjuvant Treatment for Early Breast Cancer [NCT00114816] | Phase 3 | 1,500 participants (Anticipated) | Interventional | 2004-01-31 | Completed |
| Cetuximab in Combination With Radiation Therapy and Chemotherapy Prior to Surgery in Patients With Resectable, Locally Advanced Esophageal Carcinoma. A Multicenter Phase IB-II Trial [NCT00445861] | Phase 1/Phase 2 | 27 participants (Actual) | Interventional | 2007-01-31 | Completed |
| A Phase I Study of a Chimeric Antibody Against Interleukin-6 (CNTO 328) Combined With Docetaxel in Subjects With Metastatic Hormone-Refractory Prostate Cancer [NCT00401765] | Phase 1 | 40 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Phase I/II Study With Docetaxel and Gemcitabine in Hormonal Refractory Metastatic Prostate Cancer [NCT00115635] | Phase 1/Phase 2 | 60 participants (Actual) | Interventional | 2005-03-31 | Completed |
| 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 2 | 32 participants (Actual) | Interventional | 2004-01-31 | Completed |
| A Phase I-II Study of Lapatinib and Docetaxel as Neoadjuvant Treatment for HER-2 Positive Locally Advanced/Inflammatory or Large Operable Breast Cancer [NCT00450892] | Phase 1/Phase 2 | 129 participants (Actual) | Interventional | 2007-02-28 | Completed |
| A Multicenter, Open Label, Phase II Trial Evaluating Docetaxel + Anthracycline x 4 Cycles Followed by Docetaxel Single Agent x 4 Cycles as First-Line Therapy in Patients With Her2 Negative Locally Advanced or Metastatic Breast Cancer Who Have Relapsed ≥ 1 [NCT00461344] | Phase 2 | 20 participants (Actual) | Interventional | 2004-07-31 | Terminated(stopped due to due to slow recruitment of patients) |
| Phase III, Open, Multicenter and Randomized Study of Customized Adjuvant Chemotherapy Based on BRCA1 mRNA Levels in Completely Resected Stages II-IIIA Non-Small-Cell Lung Cancer Patients [NCT00478699] | Phase 3 | 500 participants (Actual) | Interventional | 2007-06-30 | Completed |
| A Phase 1 Study Evaluating A Second Generation Antisense Oligonucleotide (OGX 427) That Inhibits Heat Shock Protein 27 (Hsp27 [NCT00487786] | Phase 1 | 64 participants (Actual) | Interventional | 2007-06-30 | Completed |
| A Phase II Trial of Docetaxel and Celecoxib in Patients With Androgen Independent Prostate Cancer [NCT00494338] | Phase 2 | 6 participants (Actual) | Interventional | 2004-11-30 | Terminated(stopped due to due to celecoxib safety issues) |
| A Prospective Phase II of Peri-Operative Docetaxel + Laparoscopic Radical Prostatectomy in Patients With Localized Gleason 7 pT2a-pT2b Adenocarcinoma and a Risk of Relapse After Radical Prostatectomy [NCT00127088] | Phase 2 | 37 participants | Interventional | 2004-10-31 | Suspended |
| A Phase I Study of the Combination of Chemoradiotherapy With Biologic Therapy for Advanced Head and Neck Cancer [NCT00405405] | Phase 1 | 13 participants (Actual) | Interventional | 2006-12-31 | Completed |
| Phase I Trial to Compare Pharmacokinetics and Safety of Docetaxel PNP With Taxotere in Subjects With Advanced Solid Tumor [NCT02274610] | Phase 1 | 18 participants (Actual) | Interventional | 2014-11-30 | Completed |
| A Phase 1, Open Label Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD2171 and Selected Chemotherapy Regimens When Given in Combination to Patients With Advanced Solid Tumors [NCT00502567] | Phase 1 | 104 participants (Actual) | Interventional | 2005-01-31 | Completed |
| TPLF-4, Compressed TPLF for Locally Advanced Squamous Cell Carcinoma [NCT00139230] | Phase 2 | 30 participants | Interventional | 1997-01-31 | Completed |
| Phase I/II Pilot Study of Induction Chemotherapy With Docetaxel in Combination With Cisplatin and 5-Fluorouracil (5-FU) in Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT00139269] | Phase 1/Phase 2 | 38 participants | Interventional | 1998-02-28 | Completed |
| Phase II Study of Docetaxel and Capecitabine as 1st Line Therapy for Patients With Locally Advanced or Metastatic Gastric Cancer [NCT00142038] | Phase 2 | 80 participants | Interventional | 2004-03-31 | Completed |
| A Prospective, Open-label, Phase I Study of Docetaxel and Nedaplatin Twice Weekly in Combination With Chest Radiotherapy in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma [NCT02964455] | Phase 1 | 12 participants (Actual) | Interventional | 2016-11-30 | Completed |
| A Pilot Trial of Germline Polymorphisms as Predictors of Response to Gemcitabine, Docetaxel, and Capecitabine (GTX) in Metastatic or Unresectable Pancreatic Cancer. [NCT00159471] | | 1 participants (Actual) | Interventional | 2005-02-28 | Terminated(stopped due to Insufficient Accrual) |
| Docetaxel and Diethylstilbestrol in the Treatment of Androgen Independent Prostate Cancer: A Phase II Study [NCT00136526] | Phase 2 | 30 participants (Actual) | Interventional | 2002-12-31 | Completed |
| Phase II Study of Bevacizumab and Docetaxel (AvaTax) in Metastatic Esophagogastric Cancer [NCT00137813] | Phase 2 | 42 participants (Actual) | Interventional | 2004-08-31 | Completed |
| Phase II Trial of Weekly Docetaxel (Taxotere®) and Carboplatin as Initial Chemotherapy for Women With Ovarian Cancer and Similar Malignancies [NCT00138242] | Phase 2 | 30 participants (Anticipated) | Interventional | 2004-12-31 | Completed |
| Multicenter Phase II Study Evaluating Docetaxel, CDDP, and Cetuximab as Induction Regimen Prior to Surgery in Chemo-naive Patients With NSCLC Stage IB, II and IIIA [NCT00406302] | Phase 2 | 41 participants (Actual) | Interventional | 2007-01-31 | Completed |
| A Phase III Study to Compare HS627 vs. Pertuzumab on the Efficacy, Safety and Immunogenicity in Combination With Trastuzumab and Docetaxel as Neoadjuvant Therapy in Patients With Early-stage or Locally Advanced HER2 Positive Breast Cancer [NCT04514419] | Phase 3 | 408 participants (Anticipated) | Interventional | 2020-06-30 | Recruiting |
| Ph III Random Trial of 120-Min Infusion Gemcitabine v. 90-Min Infusion Gemcitabine + Docetaxel in Unresectable Soft Tissue Sarcoma: A Multi-Disciplinary Trial of the North Amer. Sarcoma Study Group of the Connective Tissue Oncology Society [NCT00142571] | Phase 3 | 120 participants | Interventional | 2003-01-31 | Completed |
| Docetaxel and Carboplatin for Patients With Metastatic, Castration Resistant Prostate Cancer and Inactivated Genes in BRCA 1/2 Pathway [NCT02598895] | Phase 2 | 14 participants (Actual) | Interventional | 2016-01-26 | Completed |
| Evaluation of Thymidine Phosphorylase and Other Predictive/Prognostic Factors in Primary Breast Cancer Treated With Docetaxel and Capecitabine (DC) [NCT00156312] | | 25 participants (Anticipated) | Interventional | 2003-07-31 | Completed |
| A Phase I, Open-Label Study of the Safety, Tolerability and Pharmacokinetics of GW572016 in Combination With Docetaxel (Taxotere) [NCT00148902] | Phase 1 | 52 participants (Actual) | Interventional | 2003-04-28 | Completed |
| A Prospective Study of Adebrelimab Combined With Bevacizumab and Docetaxel in the Treatment of Advanced Non-Squamous Non-small Cell Lung Cancer After Progression on First-line Immunotherapy [NCT06182800] | Phase 2 | 35 participants (Anticipated) | Interventional | 2023-12-27 | Not yet recruiting |
| A Phase 3 Open-Label, Randomized, Controlled, Global Study of Telisotuzumab Vedotin (ABBV-399) Versus Docetaxel in Subjects With Previously Treated c-Met Overexpressing, EGFR Wildtype, Locally Advanced/Metastatic Non-Squamous Non-Small Cell Lung Cancer [NCT04928846] | Phase 3 | 698 participants (Anticipated) | Interventional | 2022-03-25 | Recruiting |
| A Phase I/II Study of M9241 With Docetaxel and Abiraterone in Adults With Metastatic Castration Sensitive and M9241 With Docetaxel in Castration Resistant Prostate Cancer [NCT04633252] | Phase 1/Phase 2 | 86 participants (Anticipated) | Interventional | 2021-02-23 | Recruiting |
| RACE-trial: Neoadjuvant Radiochemotherapy Versus Chemotherapy for Patients With Locally Advanced, Potentially Resectable Adenocarcinoma of the Gastroesophageal Junction (GEJ) A Randomized Phase III Joint Study of the AIO, ARO and DGAV [NCT04375605] | Phase 3 | 342 participants (Actual) | Interventional | 2020-06-03 | Active, not recruiting |
| 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 3 | 580 participants (Actual) | Interventional | 2019-06-27 | Completed |
| Phase II Study to Evaluate the Effectiveness and Safety of Anlotinib Combined With Docetaxel in Progress After First Line Standard Cheomotherapy in Advanced Non-driver Mutation Non- Squamous Non-small Cell Lung Cancer [NCT03646968] | Phase 2 | 43 participants (Anticipated) | Interventional | 2018-08-01 | Recruiting |
| A Phase 2 Study of Zolbetuximab (IMAB362) as Monotherapy and in Combination With Chemotherapy and/or Immunotherapy in Subjects With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma and Locoregional Gast [NCT03505320] | Phase 2 | 143 participants (Anticipated) | Interventional | 2018-06-29 | 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 3 | 1,000 participants (Anticipated) | Interventional | 2017-09-22 | Recruiting |
| A Phase I, Open-Label, Multi-center Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD6244 (ARRY-142886) When Given in Combination With Standard Doses of Selected Chemotherapies to Patients With Advanced Solid Tumors [NCT00600496] | Phase 1 | 140 participants (Actual) | Interventional | 2007-12-14 | Active, not recruiting |
| An Open-label, Randomized, Phase IIIb Trial Evaluating the Efficacy and Safety of Standard of Care +/- Continuous Bevacizumab Treatment Beyond Progression of Disease (PD) in Patients With Advanced Non-squamous Non-small Cell Lung Cancer (NSCLC) After Firs [NCT01351415] | Phase 3 | 485 participants (Actual) | Interventional | 2011-06-25 | Completed |
| A Phase II Clinical Trial of Epirubicin Plus Cyclophosphamide Followed by Docetaxel Plus Trastuzumab and Bevacizumab Given as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or Given as Adjuvant Therapy for HER2-Positive Pathologic St [NCT00464646] | Phase 2 | 105 participants (Actual) | Interventional | 2007-05-31 | Completed |
| Phase II Trial of Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients [NCT00428922] | Phase 2 | 26 participants (Actual) | Interventional | 2007-06-14 | Completed |
| A Multicentric, Randomized, Phase II Study Evaluating the Combination of METFORMIN With TAXOTERE®+Metformine Placebo Versus TAXOTERE®+Metformin for the Treatment of Metastatic Hormone-refractory Prostate Cancer. [NCT01796028] | Phase 2 | 100 participants (Actual) | Interventional | 2013-01-31 | Completed |
| 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 2 | 46 participants (Anticipated) | Interventional | 2021-03-28 | Recruiting |
| 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 2 | 41 participants (Actual) | Interventional | 2005-07-31 | Completed |
| A Randomized, Phase II Trial of AZD2171, Docetaxel, and Prednisone Compared to Docetaxel and Prednisone in Patients With Metastatic, Hormone Refractory Prostate Cancer [NCT00527124] | Phase 2 | 57 participants (Actual) | Interventional | 2007-11-30 | Terminated(stopped due to Closure was recommended by CTEP due to slow accrual.) |
| 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 1 | 500 participants (Anticipated) | Interventional | 2008-01-31 | Recruiting |
| A Multi-center, Phase II Study to Evaluate Efficacy and Safety of Perioperative Chemotherapy With Fluorouracil, Leucovorin, Oxaliplatin, Docetaxel (FLOT) and Trastuzumab in Combination With Toripalimab in Patients With HER2 Positive Locally Advanced Gastr [NCT05715931] | Phase 2 | 30 participants (Anticipated) | Interventional | 2023-02-28 | Recruiting |
| A Phase III Randomized Open-Label Study of Single Agent Pembrolizumab vs Physicians' Choice of Single Agent Docetaxel, Paclitaxel, or Irinotecan in Subjects With Advanced/Metastatic Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus That Have Pro [NCT02564263] | Phase 3 | 628 participants (Actual) | Interventional | 2015-12-01 | Completed |
| 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 2 | 45 participants (Actual) | Interventional | 2014-10-31 | Completed |
| Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors: Phase II Study of Chemotherapy, Photon and Heavy Ion Radiotherapy Integration for More Effective and Less Toxic Treatment in Inoperable Patients [NCT02099188] | Phase 2 | 27 participants (Actual) | Interventional | 2013-11-30 | Active, not recruiting |
| Multidisciplinary Approach for Poor Prognosis Sinonasal Tumors: Phase II Study of Chemotherapy, Surgery, Photon and Heavy Ion Radiotherapy Integration for More Effective and Less Toxic Treatment in Operable Patients [NCT02099175] | Phase 2 | 41 participants (Actual) | Interventional | 2013-11-30 | Active, not recruiting |
| A Randomized, Open-label, Controlled, Multicenter Phase III Study of Hydrochloride Capsule Combined With AK105 Injection Versus Standard Second-line Chemotherapy for Advanced Gastric and Gastro-oesophageal Junction Adenocarcinoma [NCT04385550] | Phase 3 | 528 participants (Anticipated) | Interventional | 2020-05-20 | Not yet recruiting |
| Phase II Study of Toripalimab Combined With Fluorouracil, Leucovorin, Oxaliplatin and Docetaxel (FLOT) in Patients With Locally Advanced, Resectable Gastric Cancer or Gastroesophageal Junction Adenocarcinoma [NCT04354662] | Phase 2 | 35 participants (Anticipated) | Interventional | 2019-09-26 | Recruiting |
| Docetaxel Plus Cisplatin Versus 5-fluorouracil Plus Cisplatin as First-line Treatment for Metastatic Esophageal Squamous Patients: a Prospective Multicenter, Randomized Controlled Clinical Study [NCT03002064] | Phase 3 | 358 participants (Anticipated) | Interventional | 2016-12-31 | Recruiting |
| Phase II Safety Study of Docetaxel and Carboplatin in Combination With Trastuzumab and Lapatinib in Early Breast Cancer [NCT00820872] | Phase 2 | 30 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Phase II Trial of Pre-Operative Docetaxel-Cytoxan (TC) in Patients With Hormone Receptor-Positive Cancers With Recurrence Scores ≥ 25 [NCT00832338] | Phase 2 | 23 participants (Actual) | Interventional | 2009-04-30 | Terminated(stopped due to Funding withdrawn) |
| An Open, Single-center, Phase II Trial of Cadonilimab Combined With Platinum-containing Dual-agent Neoadjuvant Therapy for Locally Advanced Operable Head and Neck Squamous Cell Carcinoma [NCT06023875] | Phase 2 | 30 participants (Anticipated) | Interventional | 2023-07-19 | Recruiting |
| Genomic Biomarker-Selected Umbrella Neoadjuvant Study for High Risk Localized Prostate Cancer [NCT04812366] | Phase 2 | 315 participants (Anticipated) | Interventional | 2021-09-21 | Recruiting |
| Phase II Study of Pralatrexate and Docetaxel in Patients With Advanced Esophageal and Gastroesophageal Carcinoma Who Have Failed Prior Platinum-based Therapy. [NCT01129206] | Phase 2 | 6 participants (Actual) | Interventional | 2010-07-31 | Completed |
| A Phase III, Open-Label, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Best Supportive Care Following Adjuvant Cisplatin-Based Chemotherapy in Patients With Completely Resected Stage IB-IIIA No [NCT02486718] | Phase 3 | 1,280 participants (Actual) | Interventional | 2015-10-31 | Active, not recruiting |
| Docetaxel (Taxotere) and 5-Fluorouracil As Second- Or Third-Line Chemotherapy In Women With Metastatic Breast Cancer [NCT00015886] | Phase 2 | 25 participants (Actual) | Interventional | 1997-01-31 | Completed |
| Neoadjuvant Chemotherapy With 3x Epirubicin/Docetaxel Followed by 3x Carboplatin/Docetaxel in Patients With Primary Breast Cancer [NCT00527449] | Phase 2 | 50 participants (Actual) | Interventional | 2006-05-31 | Completed |
| Phase II Study of Tailored-Dose Docetaxel + Trastuzumab in Her-2 Positive Metastatic Breast Cancer [NCT00146042] | Phase 2 | 22 participants (Actual) | Interventional | 1999-03-31 | Completed |
| An Evaluation of Estramustine, Docetaxel and Zoledronate in Patients With Hormone-Refractory Adenocarcinoma of the Prostate [NCT00151073] | Phase 2 | 28 participants (Actual) | Interventional | 2002-04-30 | Completed |
| A Randomised, Controlled, Open Phase II b Study Comparing a Combination of Dose-Intensified Doxorubicin and Docetaxel With or Without Tamoxifen as Preoperative Therapy in Patients With Operable Carcinoma of the Breast (T>=3cm N0-2 M0) [NCT00543829] | Phase 2 | 250 participants (Actual) | Interventional | 1998-04-30 | Completed |
| A Multicenter Randomized Phase II Study Evaluating the Feasibility and Activity of Two Different Combinations of Docetaxel (RP56976, TAXOTERE *) and Gemcitabine and of Cisplatin/Gemcitabine Followed by Docetaxel as First Line Therapy for Locally Advanced [NCT00191490] | Phase 2 | 162 participants | Interventional | 2002-07-31 | Completed |
| A Phase I, Open-Label Study of SB-715992 in Combination With Docetaxel in Patients With Advanced Solid Tumors. [NCT00169520] | Phase 1 | 30 participants (Actual) | Interventional | 2004-06-30 | Completed |
| A Phase III Randomized Study of Sequential Epidoxorubicin Followed By CMF: Cyclophosphamide+Methotrexate+Fluorouracil (Arm A) Versus Sequential Epidoxorubicin Followed By Docetaxel Followed By CMF (Arm B) Versus Sequential Intensified Epidoxorubicin Follo [NCT00174707] | Phase 3 | 998 participants (Actual) | Interventional | 1997-12-31 | Completed |
| Weekly Taxol® Plus Xeloda® Versus Taxotere® Every Three Weeks Plus Xeloda® in the Treatment of Metastatic Breast Cancer A Phase II/III Study [NCT00201435] | Phase 2/Phase 3 | 224 participants (Anticipated) | Interventional | 2005-03-31 | Completed |
| A Phase Ib, Pharmacokinetic, Multiple Center, Open Label Study Evaluating the Safety and Efficacy of Mycograb Administered IV in Combination With Docetaxel in Metastatic or Recurrent Breast Cancer Patients [NCT00217815] | Phase 1/Phase 2 | 20 participants | Interventional | 2005-09-30 | Completed |
| Gene Expression Profiles of Breast Cancer Treated With Sequential Adriamycin and Docetaxel in Relation to Tumor Responses [NCT00212082] | Phase 2 | 100 participants | Interventional | 2002-04-30 | Completed |
| Real World Evidence Study on Metastatic Prostate Cancer Patient Characteristics, Treatment Patterns and Outcomes in the Pirkanmaa Hospital District in Finland [NCT05701007] | | 1 participants (Actual) | Observational | 2023-02-13 | Completed |
| Phase 1 Study of Cemiplimab - TP Induction Chemotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT05376553] | Phase 1 | 24 participants (Anticipated) | Interventional | 2022-06-16 | Recruiting |
| A Phase II Randomized Trial Of Gemcitabine Plus Paclitaxel And Gemcitabine Plus Docetaxel In Patients With Metastatic Breast Cancer [NCT00191672] | Phase 2 | 120 participants | Interventional | 2003-12-31 | Completed |
| Patterns of Genetic Expression Associated to Sensibility to Doxorubicin Versus Docetaxel as Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer [NCT00123929] | Phase 2 | 250 participants (Anticipated) | Interventional | 2005-01-31 | Completed |
| A Single Arm Phase II Trial of Docetaxel and Capecitabine for the First Line Treatment of Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN): Hoosier Oncology Group HN02-40 [NCT00216138] | Phase 2 | 19 participants (Actual) | Interventional | 2004-03-31 | Terminated(stopped due to Interim analysis results did not meet criteria for second stage of trial) |
| A Phase I Study of Cetuximab/Docetaxel(Taxotere)/Cisplatin/5-Fluorouracil (C-TPF) in Patients With Newly Diagnosed Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT00402545] | Phase 1 | 29 participants (Anticipated) | Interventional | 2007-01-31 | Completed |
| Phase II Trial- Weekly Taxotere and Topotecan for Recurrent Ovarian, Primary Peritoneal, Endometrial and Uterine Cancers [NCT00231855] | Phase 2 | 31 participants | Interventional | 2004-11-30 | Completed |
| Phase II Evaluation of Weekly Docetaxel in Combination With Weekly Carboplatin in the Treatment of Recurrent Epithelial Ovarian Carcinoma [NCT00214058] | Phase 2 | 36 participants | Interventional | 2002-08-31 | Completed |
| A Single-arm Exploratory Clinical Study of Anlotinib Hydrochloride Combined With Docetaxel in EGFR Mutations Advanced Non Small Cell Lung Cancer Patients Who Have Progressed After Targeted Therapy and Chemotherapy [NCT04619563] | Phase 2 | 42 participants (Anticipated) | Interventional | 2020-11-04 | Recruiting |
| Phase I Trial of Three-Weekly Docetaxel, Carboplatin and Oral CC-5013 in Patients With Advanced Solid Tumors [NCT00415116] | Phase 1 | 14 participants (Actual) | Interventional | 2004-08-31 | Completed |
| A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Phase 2 Study Comparing AT-101 in Combination With Docetaxel and Prednisone Versus Docetaxel and Prednisone in Men With Chemotherapy-Naïve Metastatic Hormone Refractory Prostate Cancer (HRPC) [NCT00571675] | Phase 2 | 220 participants (Actual) | Interventional | 2007-10-31 | Completed |
| A Dose Escalation, Expansion Study of Vofatamab (B-701) Alone, Plus Docetaxel, or Versus Docetaxel in Subjects With Locally Advanced or Metastatic Urothelial Cell Carcinoma Who Have Relapsed After, or Are Refractory to Standard Therapy [NCT02401542] | Phase 1/Phase 2 | 71 participants (Actual) | Interventional | 2015-06-30 | Terminated(stopped due to program has been put on hold by the sponsor) |
| Feasibility of Dose Titrating Paricalcitol (Zemplar) in Women Receiving Taxanes or Ixabepilone for Metastatic Breast Cancer [NCT00637897] | Phase 1 | 24 participants (Actual) | Interventional | 2008-03-31 | Completed |
| An Open-Label, Multicenter, Randomized Phase 2 Study Evaluating the Safety and Efficacy of Docetaxel in Combination With Ramucirumab (IMC-1121B) Drug Product or IMC-18F1 or Without Investigational Therapy as Second-line Therapy in Patients With Locally Ad [NCT01282463] | Phase 2 | 148 participants (Actual) | Interventional | 2011-04-30 | Completed |
| A Phase 1b Study of Docetaxel in Combination With Ramucirumab (IMC-1121B) Drug Product in Patients With Locally Advanced or Metastatic Breast Cancer [NCT01256567] | Phase 1 | 7 participants (Actual) | Interventional | 2010-12-31 | Completed |
| 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 2 | 38 participants (Actual) | Interventional | 2006-03-31 | Terminated(stopped due to Due to Poor Accrual) |
| Biochemical Recurrence Rate of Radical Prostatectomy Combined With Neoadjuvant and Adjuvant in Patients With High Risk Locallized Prostate Cancer [NCT01530295] | | 70 participants (Anticipated) | Interventional | 2008-07-31 | Recruiting |
| Phase I/II Trial of ZD1839 (Iressa®), Trastuzumab (Herceptin®), and Docetaxel (Taxotere®) in Patients With erbB-2 (HER-2) Overexpressing, Stage IV Breast Carcinoma [NCT00086957] | Phase 1/Phase 2 | 31 participants (Actual) | Interventional | 2004-01-31 | Completed |
| Pharmacodynamic Trial: Molecular Marker & Imaging Studies as Primary Endpoints to Determine Optimal Biological Dosage of Perifosine, Orally Avail AKT PH Domain Inhibitor Combined w/ Docetaxel in Patients w/Relapsed Epithelial Ovarian Cancer [NCT00431054] | Phase 1 | 22 participants (Actual) | Interventional | 2007-02-28 | Completed |
| Study Evaluating the Contribution of MRI for the Evaluation of Early Response to Neoadjuvant Chemotherapy in Patients With Infiltrative Breast Cancer [NCT00462696] | | 30 participants (Anticipated) | Interventional | 2006-02-28 | Completed |
| A Phase II Randomized Crossover Study Doxorubicin HCI Liposome Injection Versus Weekly Docetaxel in Patients First Relapse Metastatic Breast Cancer [NCT00193037] | Phase 2 | 102 participants (Actual) | Interventional | 2001-02-28 | Completed |
| A Randomized, Open-label, Multi-center Study of Larotaxel at 90mg/m2 or Docetaxel Every 3 Weeks, Alone or in Combination With Trastuzumab According to Her2neu Status, Administered After a Combination of Anthracycline and Cyclophosphamide as Pre-operative [NCT00485979] | Phase 2 | 330 participants (Actual) | Interventional | 2007-06-30 | Completed |
| Phase II Trial of Docetaxel, Oxaliplatin and Capecitabine (TEX) in Advanced or Metastatic Gastric Cancer [NCT00511446] | Phase 2 | 56 participants (Actual) | Interventional | 2007-08-31 | Completed |
| A Phase II Trial to Assess the Activity of MVA 5T4 (Trovax®) Plus Docetaxel Versus Docetaxel Alone in Patients With Progressive Hormone Refractory Prostate Cancer (HRPC) [NCT00521274] | Phase 2 | 11 participants (Actual) | Interventional | 2007-08-31 | Terminated(stopped due to Oxford BioMedica halted TroVax injections) |
| A Chinese Multi-Center,Randomized Study of Combination or Sequential Use of Docetaxel,Anthracycline and Cyclophosphamide in Adjuvant Therapy for Node Positive Breast Cancer [NCT00525642] | Phase 2/Phase 3 | 603 participants (Actual) | Interventional | 2003-06-30 | Active, not recruiting |
| Safety and Efficacy (Phase II) Study of Concurrent Cetuximab Plus Conformal Thoracic Radiotherapy in (Poor Prognosis) Patients With Inoperable or Unresectable, Locally Advanced Non-Small Cell Lung Cancer (LA - NSCLC) [NCT00673738] | Phase 2 | 27 participants (Actual) | Interventional | 2008-04-30 | Completed |
| Neoadjuvant and Concurrent Chemoradiotherapy Plus Nimotuzumab in Treating Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Oropharynx and Hypopharynx [NCT01516996] | Phase 2 | 80 participants (Anticipated) | Interventional | 2012-03-31 | Recruiting |
| A Multicenter Phase II Study of Neoadjuvant Docetaxel, Cisplatin and Capecitabine and Protocolized Surgery in Resectable Gastric Cancer [NCT01517009] | Phase 2 | 50 participants (Anticipated) | Interventional | 2008-06-30 | Completed |
| 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 3 | 1,736 participants (Anticipated) | Interventional | 2023-06-01 | 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 3 | 382 participants (Anticipated) | Interventional | 2023-12-15 | Not yet recruiting |
| A Pilot Trial of Pembrolizumab Plus Chemoradiotherapy in Participants With Unresectable Gastroesophageal Cancer [NCT04522336] | Phase 1 | 15 participants (Anticipated) | Interventional | 2020-09-16 | Recruiting |
| Phase II, Open-label, Single-center Study Evaluating Safety and Activity of Androgen Deprivation Therapy Followed by Chemoimmunotherapy for Newly Metastatic Hormone-sensitive Prostate Cancer (mHSPC) [NCT03951831] | Phase 2 | 20 participants (Anticipated) | Interventional | 2019-05-16 | Active, not recruiting |
| A Phase I-II Study of Systemic Capecitabine, Cisplatin and Intraperitoneal Docetaxel (XPID) in Patients With Advanced Stomach Cancer With Peritoneal Seeding [NCT01525771] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2011-02-28 | Completed |
| A Phase II Study of Weekly 24-hour Infusion 5-fluoro-deoxyuridine (FUdR)/Leucovorin With Oxaliplatin and Docetaxel (Taxotere) as First-line Treatment in Patients With Metastatic Gastric Adenocarcinoma (IIT# 14065) [NCT00448682] | Phase 2 | 25 participants (Actual) | Interventional | 2005-06-30 | Terminated |
| [NCT01526499] | Phase 2 | 60 participants (Anticipated) | Interventional | 2011-12-31 | Recruiting |
| Cisplatin and 5-fluorouracil(PF) or Docetaxel,Cisplatin and 5-fluorouracil (TPF) Neoadjuvant Chemotherapy With Chemoradiation Therapy for Locally Advanced Nasopharyngeal Carcinoma--A Randomised Prospective Multicenter Phase 3 Study [NCT01536223] | Phase 3 | 400 participants (Anticipated) | Interventional | 2012-04-30 | Recruiting |
| Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide in Locally Advanced or Node Positive Primary Breast Cancer With Companion Pharmacokinetic and Pharmacogenomic Analyses [NCT01540110] | Phase 2 | 21 participants (Actual) | Interventional | 2010-08-11 | Completed |
| Multicenter Prospective Randomized Phase III Trial Comparing Elective to Prophylactic Regional Lymph Node Irradiation for Thoracic Esophageal Cancer [NCT01551589] | | 220 participants (Actual) | Interventional | 2012-03-31 | Completed |
| Neoadjuvant Chemotherapy With Docetaxel in Advanced Cervical Carcinoma [NCT00003445] | Phase 2 | 0 participants | Interventional | 1997-12-31 | Completed |
| A Randomized Phase II-III Multicenter Trial of Docetaxel Plus Cisplatin and Docetaxel Plus 5-FU Versus Cisplatin Plus 5-FU in 1st Line Treatment of Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck. [NCT00401323] | Phase 2/Phase 3 | 568 participants (Actual) | Interventional | 1998-01-31 | Completed |
| A Phase II Trial of Weekly, Low-Dose Docetaxel (Taxotere) in Patients With Platinum-Resistant Epithelial Ovarian or Primary Peritoneal Serous Cancer [NCT00004081] | Phase 2 | 30 participants (Actual) | Interventional | 1999-07-31 | Completed |
| Phase I Evaluation of Erlotinib and Docetaxel With Concomitant Boost Radiation for Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT00113347] | Phase 1 | 10 participants (Actual) | Interventional | 2005-04-30 | Completed |
| Phase I Trial of Intrapleural Docetaxel Administered Via an Implantable Catheter in Subjects With a Malignant Pleural Effusion [NCT00114205] | Phase 1 | 24 participants (Anticipated) | Interventional | 2003-07-31 | Completed |
| A Randomized, Double-Blind, Phase 2 Study Evaluating the Safety of Same Day Versus Next Day Administration of Pegfilgrastim With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) in Women With Breast Cancer [NCT00115414] | Phase 2 | 0 participants | Interventional | | Completed |
| Phase III Study Comparing the Use of Docetaxel on a Every Three-Week vs. Weekly Schedule in the Treatment of Patients With Metastatic Breast Cancer [NCT00008411] | Phase 3 | 90 participants (Actual) | Interventional | 1999-12-31 | Completed |
| A Phase II Trial of Docetaxel Plus Cetuximab and Docetaxel Plus Bortezomib (NSC #681239, IND #58443) in Advanced Non-Small Cell Lung Cancer Patients With Performance Status (PS) 2 [NCT00118183] | Phase 2 | 62 participants (Actual) | Interventional | 2005-07-31 | Completed |
| Carcinoma Unknown Primary: Treatment With Gemcitabine, Docetaxel and Capecitabine (GTX) an Evaluation and Treatment Study of The Cancer Institute of New Jersey Oncology Group [NCT00119314] | Phase 2 | 0 participants (Actual) | Interventional | 2004-07-31 | Withdrawn(stopped due to slow accrual) |
| A Phase I/II Trial of Docetaxel Followed by Infusional Flavopiridol Over 72 Hours in Patients With Previously Treated Locally Advanced or Metastatic Breast Cancer [NCT00020332] | Phase 1/Phase 2 | 0 participants | Interventional | 2000-10-31 | Completed |
| A Multicenter Randomized Trial of Sequential Epirubicin and Docetaxel Versus Epirubicin in Node Positive Postmenopausal Breast Cancer Patients [NCT00010140] | Phase 3 | 0 participants | Interventional | 1997-08-31 | Active, not recruiting |
| Phase 1 Trial of Dose Escalated BGB324 in Combination With Docetaxel for Previously Treated Advanced Non-small Cell Lung Cancer (NSCLC) [NCT02922777] | Phase 1 | 23 participants (Actual) | Interventional | 2016-11-30 | Active, not recruiting |
| A Phase II Study Using SGN-15 (cBR96 - Doxorubicin Immunoconjugate) in Combination With Taxotere for the Treatment of Metastatic or Recurrent Breast Carcinoma [NCT00028483] | Phase 2 | 0 participants | Interventional | 2000-10-31 | Terminated |
| An EORTC-IDBBC/ECSG Phase II Study Evaluating The Role Of The Multi-Drug Resistance (MDR) Reversor, R101933, In Patients With Taxane Refractory Metastatic Breast Cancer [NCT00028873] | Phase 2 | 35 participants (Actual) | Interventional | 2001-09-30 | Completed |
| Efficacy and Safety Study of the Combined Modality Therapy in Patients With Potentially Resectable, Locally Advanced Adenocarcinoma of the Esophago-gastric Junction With Preoperative Chemo- and Chemoradiation Followed by Surgical Resection [NCT01523015] | Phase 2/Phase 3 | 100 participants (Anticipated) | Interventional | 2012-01-31 | Recruiting |
| Phase ll Trial of Docetaxel/Pembrolizumab Combination Treatment in Patients With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma [NCT05252429] | Phase 2 | 27 participants (Anticipated) | Interventional | 2022-07-06 | Recruiting |
| Phase II Trial of Concurrent Cisplatin/Docetaxel and Radiotherapy Followed by Consolidation Docetaxel in Stage IIIB Non-Small Cell Lung Cancer [NCT00014196] | Phase 2 | 33 participants (Actual) | Interventional | 2001-03-31 | Terminated(stopped due to This study was closed early due to poor accrual.) |
| Phase II Trial Of Sequential Estramustine/Paclitaxel Followed By Doxorubicin/Ketoconazole In Patients With Androgen-Independent Prostate Cancer [NCT00014352] | Phase 2 | 0 participants | Interventional | 2000-09-30 | Completed |
| A Phase II Study Of Estramustine, Docetaxel, And Bevacizumab (IND # 7921, NSC # 704865) In Men With Hormone Refractory Prostate Cancer [NCT00016107] | Phase 2 | 72 participants (Actual) | Interventional | 2001-06-30 | Completed |
| Phase I Study Of Flavopiridol And Docetaxel (Taxotere) In Patients With Advanced Cancers [NCT00016185] | Phase 1 | 0 participants | Interventional | 2001-03-31 | Completed |
| A Phase II Trial Of Exisulind With Docetaxel In Patients With Metastatic Adenocarcinoma Of The Breast [NCT00039520] | Phase 2 | 10 participants (Actual) | Interventional | 2002-01-31 | Completed |
| Docetaxel And Infliximab/Placebo In Non-Small Cell Lung Cancer (NSCLC) Patients Greater Than Or Equal To 65 Years Of Age Or In NSCLC Patients With Poor Performance Status: A Double-Blind Randomized, Placebo-Controlled Trial To Prevent And Treat Wasting, A [NCT00040885] | Phase 3 | 67 participants (Actual) | Interventional | 2002-10-31 | Completed |
| A Phase I Study Of OSI-774 (NSC #718781)-Based Multimodality Therapy For Inoperable Stage III Non Small Cell Lung Cancer [NCT00042835] | Phase 1 | 48 participants (Actual) | Interventional | 2002-05-31 | Terminated(stopped due to Administratively complete.) |
| A Randomized Study Comparing 4 Monthly Doses of MDX-010 (CTLA-4) as a Single Agent or Used in Combination With a Single Dose of Docetaxel in Patients With Hormone-Refractory Prostate Cancer [NCT00050596] | Phase 2 | 0 participants | Interventional | 2002-11-30 | Completed |
| A Phase II Study Using SGN-15 (cBR96-Doxorubicin Immunoconjugate) in Combination With Docetaxel for the Treatment of Advanced Stage or Recurrent Non-Small Cell Lung Carcinoma [NCT00051571] | Phase 2 | 60 participants | Interventional | | Completed |
| Randomized And Multicentric Phase III Study Evaluating The Benefit By Using A Chemotherapy With FEC 100 And Docetaxel In Non Metastatic Breast Cancer Which Has Relapsed After A Conservative Surgery [NCT00053911] | Phase 3 | 0 participants | Interventional | 2002-11-30 | Terminated |
| CT-2103 vs Docetaxel for the Second-Line Treatment of Non-Small Cell Lung Cancer (NSCLC): A Phase III Study [NCT00054184] | Phase 3 | 350 participants (Anticipated) | Interventional | 2003-01-31 | Terminated |
| A Phase II Study Of Docetaxel And Capecitabine In Patients With Measurable Metastatic Adenocarcinoma Of The Stomach And Gastroesophageal Junction [NCT00054457] | Phase 2 | 46 participants (Actual) | Interventional | 2003-09-30 | Completed |
| A Phase I Study of Intravenous LB-100 for Injection as a Single Agent and in Combination With Docetaxel in the Treatment of Patients With Advanced Solid Tumors [NCT01837667] | Phase 1 | 29 participants (Actual) | Interventional | 2013-02-28 | Completed |
| PHASE 2 STUDY OF BEVACIZUMAB IN COMBINATION WITH DOCETAXEL IN PATIENTS WITH ADVANCED BREAST CANCER [NCT00055861] | Phase 2 | 27 participants (Actual) | Interventional | 2002-07-31 | Completed |
| Definitive Concurrent Chemoradiotherapy With Docetaxel Plus Cisplatin Versus 5-fluorouracil Plus Cisplatin in Patients With Esophageal Squamous Cell Carcinoma: a Phase II Randomized Controlled Trial [NCT02969473] | Phase 2 | 120 participants (Anticipated) | Interventional | 2010-10-31 | Active, not recruiting |
| A Randomized, Multicenter, Open-Label, Phase II Study Of VELCADE Alone Or VELCADE Plus Docetaxel In Previously Treated Patients With Advanced Non-Small Cell Lung Cancer [NCT00064012] | Phase 2 | 4 participants (Actual) | Interventional | 2003-05-31 | Completed |
| Phase Ib/II Neoadjuvant Trial of the Farnesyltransferase Inhibitor, R115777 With Docetaxel and Capecitabine for Patients With Stage IIIA or IIIB Breast Cancer [NCT00070252] | Phase 1/Phase 2 | 53 participants (Actual) | Interventional | 2003-09-30 | Completed |
| Phase II Study Of Gemcitabine And Docetaxel In Patients With Inoperable Stage IIIB Or IIIB or IV Non-Small Cell Lung Cancer [NCT00075517] | Phase 2 | 0 participants | Interventional | 2003-09-30 | Active, not recruiting |
| A Phase II Randomized Study Of Dose-Dense Docetaxel And Cisplatin Every Two Weeks With Pegfilgrastim And Darbepoetin Alfa With And Without The Chemoprotector BNP7787 In Patients With Advanced Non-Small Cell Lung Cancer [NCT00077311] | Phase 2 | 160 participants (Actual) | Interventional | 2004-08-31 | Completed |
| Phase 2 Study of Talabostat and Docetaxel in Advanced Non-Small Cell Lung Cancer [NCT00080080] | Phase 2 | 0 participants | Interventional | | Completed |
| A Pilot Study Assessing Patterns of Response or Resistance to Preoperative Dose Dense Docetaxel in Women With Newly Diagnosed Breast Cancer [NCT00080626] | Phase 2 | 19 participants (Actual) | Interventional | 2003-08-11 | Terminated(stopped due to low accrual) |
| A Phase I Study Of Weekly Taxotere (Docetaxel) And Gleevec (STI571, Imatinib Mesylate, CGP 57148B) In Locally Advanced Or Metastatic Breast Cancer [NCT00080665] | Phase 1 | 12 participants (Actual) | Interventional | 2003-12-31 | Completed |
| A Phase II Trial Combining Estramustine, Docetaxel And Thalidomide In Patients With Androgen-Independent Metastatic Prostate Cancer [NCT00083005] | Phase 2 | 60 participants (Anticipated) | Interventional | 2004-03-31 | Completed |
| Positron Emission Tomography Pre- and Post-treatment Assessment For Locally Advanced Non-Small Cell Lung Carcinoma [NCT00083083] | Phase 2 | 250 participants (Anticipated) | Interventional | 2005-03-31 | Active, not recruiting |
| A Phase II Study of Docetaxel in Combination With ZD 1839 (IRESSA) in Previously Treated Patients With Metastatic Pancreatic Cancer [NCT00137761] | Phase 2 | 32 participants (Actual) | Interventional | 2004-10-31 | Completed |
| A Phase I/II Study of Taxotere, Cisplatin, 5-Fluorouracil and Leucovorin for Squamous Cell Carcinoma of the Head and Neck [NCT00139243] | Phase 1/Phase 2 | 30 participants | Interventional | 1997-10-31 | Completed |
| A Multicenter Randomized Phase II Study Evaluating The Activity And Tolerability Of Three Different Combinations Of Docetaxel (Taxotere) And Irinotecan (Campto) As Second Line Therapy For Recurrent Or Metastatic Non Small Cell Lung Cancer (NSCLS) [NCT00139711] | Phase 2 | 138 participants | Interventional | 2003-03-31 | Completed |
| A Multi-centre, Randomised, Parallel Group, Open-label, Phase II, Single-stage Selection Trial of Liposomal Irinotecan (Nal-IRI) and 5-fluorouracil (5-FU)/Folinic Acid or Docetaxel as Second-line Therapy in Patients With Progressive Poorly Differentiated [NCT03837977] | Phase 2 | 102 participants (Anticipated) | Interventional | 2018-11-13 | Active, not recruiting |
| A Post-marketing Surveillance Study to Evaluate the Effectiveness and Safety of Docetaxel-Based Chemotherapy [NCT02972216] | | 40 participants (Actual) | Observational | 2014-11-30 | Completed |
| Multi-Cycle High-Dose Chemotherapy Versus Optimized Conventionally-Dosed Chemotherapy in Patients With Metastatic Breast Cancer: A Phase II Prospective Randomized Trial [NCT00012311] | Phase 2 | 0 participants | Interventional | 2000-01-31 | Active, not recruiting |
| A Phase II Trial of Evaluating Circulating Endothelial Cell as A Surrogate Marker for Monitoring Treatment Efficacy of Docetaxel Plus Capecitabine With Bevacizumab as First Line Treatment for Patients With Locally Recurrent and Metastatic Breast Cancer [NCT00845910] | Phase 2 | 22 participants (Actual) | Interventional | 2009-05-31 | Terminated(stopped due to To be confirmed) |
| Phase II Trial of Gemcitabine And Docetaxel In Androgen-Independent Metastatic Prostate Cancer [NCT00276549] | Phase 2 | 35 participants (Actual) | Interventional | 2005-10-31 | Completed |
| A Dose-Escalation Trial Of The Combination Of Docetaxel, Gemcitabine And Filgrastim (NEUPOGEN) For The Treatment Of Patients With Advanced Solid Tumors [NCT00014456] | Phase 1 | 35 participants (Actual) | Interventional | 2000-03-31 | Completed |
| Docetaxel And Vinorelbine Plus Filgrastim For HER-2 Negative, Stage IV Breast Cancer [NCT00015938] | Phase 2 | 95 participants (Actual) | Interventional | 2001-05-31 | Completed |
| A Phase III Trial of Cisplatin/Etoposide/Radiotherapy With Consolidation Docetaxel Followed by Maintenance Therapy With ZD1839 (NSC-715055) or Placebo in Patients With Inoperable Locally Advanced Stage III Non-Small Cell Lung Cancer [NCT00020709] | Phase 3 | 840 participants (Actual) | Interventional | 2001-06-30 | Completed |
| A Randomized Phase II Study of Bevacizumab in Combination With Docetaxel in Locally Advanced Breast Cancer [NCT00027885] | Phase 2 | 49 participants (Actual) | Interventional | 2001-11-30 | Completed |
| Evaluation Of Celecoxib In Combination With Docetaxel In The Treatment Of Advanced Non-Small Cell Lung Cancer Patients Previously Treated With Platinum Based Chemotherapy [NCT00030420] | Phase 2 | 24 participants (Actual) | Interventional | 2001-10-31 | Completed |
| A Phase III Randomized Study of Patients With High Risk, Hormone-Naive Prostate Cancer: Androgen Blockade With 4 Cycles of Immediate Chemotherapy Versus Androgen Blockade With Delayed Chemotherapy [NCT00030654] | Phase 3 | 21 participants (Actual) | Interventional | 2002-10-31 | Completed |
| Safety of Extended Use of ModraDoc006/r in Patients With Advanced Solid Tumours [NCT03150368] | Phase 1 | 17 participants (Actual) | Interventional | 2017-05-10 | Completed |
| A Phase III Randomized Trial Assessing the Utility of a Test Dose Program With Taxanes [NCT00277043] | Phase 3 | 200 participants (Actual) | Interventional | 2002-06-30 | Completed |
| Prospective, Open-Label, Randomized Study of Combination Therapy of MYOCET® Plus Cyclophosphamide and Trastuzumab Versus Free Doxorubicin Plus Cyclophosphamide Alone, Each Followed by Docetaxel and Trastuzumab, in Neoadjuvant Setting in Treatment-Naive Pa [NCT00712881] | Phase 2 | 126 participants (Actual) | Interventional | 2008-10-13 | Completed |
| Phase II Trial of Docetaxel With PI-88 in Patients With Advanced Non-Small-Cell Lung Cancer [NCT00097851] | Phase 2 | 100 participants | Interventional | 2004-02-29 | Completed |
| Randomized, Open Label, Multicentric Phase III Evaluating the Benefit of a Sequential Regimen Associating FEC 100 and Ixabepilone in Adjuvant Treatment of Non Metastatic, Poor Prognosis Breast Cancer Defined as Triple-negative Tumor [HER2 Negative - ER Ne [NCT00630032] | Phase 3 | 762 participants (Actual) | Interventional | 2007-09-30 | Completed |
| A Phase II Study of Docetaxel (Taxotere) (NSC# 628503, IND# 59,761) in Children With Refractory Leukemias [NCT00021242] | Phase 2 | 12 participants (Actual) | Interventional | 2002-08-31 | Completed |
| Phase I Pharmacokinetic Trial of Thalidomide and Docetaxel: A Regimen Based on Anti-Angiogenic Therapeutic Principles [NCT00049296] | Phase 1 | 26 participants (Actual) | Interventional | 2002-07-31 | Completed |
| Docetaxel In Second-Line Treatment Of Advanced Non-Small-Cell Lung Cancer - The Distal Study [NCT00022022] | Phase 3 | 200 participants (Anticipated) | Interventional | 2000-12-31 | Active, not recruiting |
| A Phase II Study Of Estramustine, Docetaxel, And Exisulind (IND #64733) In Men With Hormone Refractory Prostate Cancer [NCT00052845] | Phase 2 | 80 participants (Actual) | Interventional | 2002-11-30 | Completed |
| Single Agent Docetaxel for Metastatic Breast Cancer in Patients Aged 70 Years and Older (and in a Cohort of Patients Younger Than 60 Years) [NCT00025493] | Phase 2 | 27 participants (Actual) | Interventional | 2001-10-31 | Terminated(stopped due to poor accrual) |
| Phase II Trial of Sequential Vinorelbine and Docetaxel in Advanced Non-Small Cell Lung Cancer Patients Age Seventy and Older, or With Performance Status 2 [NCT00026156] | Phase 2 | 125 participants (Actual) | Interventional | 2001-11-30 | Completed |
| A Phase I and Phase II Study of OSI-774 in Combination With Docetaxel in Squamous Cell Carcinoma of the Head and Neck [NCT00055770] | Phase 1/Phase 2 | 45 participants (Anticipated) | Interventional | 2002-10-31 | Completed |
| Evaluation Of Celecoxib In Combination With Weekly Docetaxel In Elderly (70 Years) Or Poor Performance Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) [NCT00030407] | Phase 2 | 34 participants (Actual) | Interventional | 2001-10-31 | Completed |
| Phase I/II Study of Docetaxel and OSI-774 (Erlotinib) in Solid Tumor Patients With an Emphasis on NSCLC Using Molecular Correlates as Potential Markers of Response [NCT00390429] | Phase 1/Phase 2 | 81 participants (Actual) | Interventional | 2002-07-31 | Completed |
| A Phase I Trial of High Dose Ketoconazole Plus Weekly Docetaxel in Metastatic Androgen Independent Prostate Cancer [NCT00032825] | Phase 1 | 674 participants (Actual) | Interventional | 2002-03-19 | Completed |
| A Randomised Trial Of Standard Anthracycline-Based Chemotherapy With Fluorouracil, Epirubicin And Cyclophosphamide (FEC) Or Epirubicin And CMF (Epi-CMF) Versus FEC Followed By Sequential Docetaxel As Adjuvant Treatment For Women With Early Breast Cancer [NCT00033683] | Phase 2 | 0 participants | Interventional | 2001-02-28 | Active, not recruiting |
| A Multicenter, Open-Label, Phase II Trial of Adjuvant Taxotere in Patients At High Risk of Relapse Following Prostatectomy [NCT00069888] | Phase 2 | 83 participants (Actual) | Interventional | 2001-11-30 | Completed |
| 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 2 | 116 participants (Actual) | Interventional | 2003-05-31 | Completed |
| A Pilot Study of Low Dose Suramin as Modulator of Docetaxel and Gemcitabine in Patients With Previously Treated Non-Small Cell Lung Cancer (NSCLC) [NCT00066768] | Phase 1 | 24 participants (Actual) | Interventional | 2003-07-31 | Completed |
| A Phase 1/2 Multicenter, Open Label, Dose Ranging Study of DN-101 and Taxotere® in Patients With Advanced (Stage IIIB or IV) Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Previous Therapy With Platinum-Based Chemotherapy [NCT00066885] | Phase 1/Phase 2 | 80 participants | Interventional | 2003-06-30 | Completed |
| Randomized Blinded Phase III Assessment of Second or Third-Line Chemotherapy With Docetaxel + Plinabulin Compared to Docetaxel + Placebo in Patients With Advanced Non-Small Cell Lung Cancer and With at Least One Measurable Lung Lesion [NCT02504489] | Phase 3 | 559 participants (Actual) | Interventional | 2015-12-31 | Completed |
| Docetaxel and Cisplatin Chemo- and Radiochemotherapy Followed by Surgery in Patients With Locally Advanced Esophageal Cancer - A Multicenter Phase II Trial [NCT00072033] | Phase 2 | 66 participants (Actual) | Interventional | 2003-03-31 | Completed |
| TPExtreme: Randomized, Controlled Trial of Platinum-Cetuximab Combined Either With Docetaxel (TPEx) or With 5FU (Extreme) in Patients With Recurrent/Metastatic Squamous Cell Cancer of the Head and Neck [NCT02268695] | Phase 2 | 541 participants (Actual) | Interventional | 2014-10-10 | Completed |
| A Phase II Study of Docetaxel and Epirubicin Combination in Patients With Advanced Gastric Cancer. [NCT00375999] | Phase 2 | 34 participants (Actual) | Interventional | 2006-09-30 | Completed |
| Phase II, Randomized, Open-Label, Two-Arm, Multicenter Study of MEDI-522, a HuMA Directed Against the Human Alpha V Beta 3 Integrin, in Combination With Docetaxel, Prednisone, and Zoledronic Acid in the Treatment of Patients With Metastatic Androgen-Indep [NCT00072930] | Phase 2 | 150 participants | Interventional | 2003-12-31 | Completed |
| A Multicenter Randomized Phase III Study of Adjuvant Treatment With Epirubicin Followed by Docetaxel (E/T) Versus Epirubicin and Docetaxel Combination (ET) in High Risk Lymph Node Negative Breast Cancer Patients [NCT00424606] | Phase 3 | 658 participants (Actual) | Interventional | 2001-06-30 | Completed |
| A Phase II Evaluation Of Docetaxel (NSC #628503) In The Treatment Of Persistent Or Recurrent Squamous Cell Carcinoma Of The Cervix [NCT00041093] | Phase 2 | 27 participants (Actual) | Interventional | 2002-06-30 | Completed |
| A Phase 1 Trial of the Combination of Perifosine and Docetaxel With or Without Prednisone [NCT00399087] | Phase 1 | 39 participants (Actual) | Interventional | 2004-11-30 | Completed |
| Phase III Randomized Study of Hypericum Perforatum (St. John's Wort) Combined With Docetaxel in Patients With Unresectable Solid Tumors [NCT00041171] | Phase 3 | 0 participants (Actual) | Interventional | | Withdrawn(stopped due to The study was not activated.) |
| Phase I/II Study of Docetaxel, Cisplatin and 5-fluorouracil(TPF) as Chemotherapy in Pre-treated Patients With Metastatic Esophageal Cancer. [NCT00209716] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2003-12-31 | Completed |
| Phase II Study of Docetaxel Combined With Ketoconazole in the First-line Treatment of Locally Advanced or Metastatic Breast Cancer Patients With Measurable Primary Breast Tumor [NCT00212095] | Phase 2 | 30 participants (Actual) | Interventional | 2005-06-30 | Completed |
| Efficacy of Docetaxel (J 15) and Celecoxib in Metastatic Prostate Cancer [NCT00213694] | | 52 participants | Observational | 2003-11-30 | Completed |
| Imatinib Mesylate (Gleevec®, STI571) in Combination With Docetaxel (Taxotere) for the Treatment of Advanced, Platinum-Refractory Ovarian Cancer and Primary Peritoneal Carcinomatosis: Hoosier Oncology Group GYN03-62 [NCT00216112] | Phase 2 | 23 participants (Actual) | Interventional | 2003-12-31 | Completed |
| A Phase I/2 Study of GTI-2040 Combined With Docetaxel In Metastatic Or Unresectable Locally Advanced Non-Small Cell Lung Cancer [NCT00074022] | Phase 1/Phase 2 | 48 participants (Actual) | Interventional | 2003-10-31 | Completed |
| A Pharmacokinetic Interaction Study Of Docetaxel (Taxotere) 75 mg/mIV On The Combination Therapy Doxorubicin (50 mg/m) And Cyclophosphamide (50 mg/m) In The Treatment Of Advanced Breast Cancer [NCT00074139] | Phase 1 | 0 participants (Actual) | Interventional | 2003-09-30 | Withdrawn(stopped due to No patients were enrolled) |
| A Pilot Trial of Pox Vector PSA Vaccine With Concurrent Docetaxel Versus Pox Vector Vaccine Followed by Docetaxel in Metastatic Androgen Independent Prostate Cancer [NCT00045227] | Phase 2 | 0 participants | Interventional | 2002-08-31 | Completed |
| A Pilot Study to Evaluate the Influence of Garlic on the Pharmacokinetics of Docetaxel in Patients With Metastatic Breast Cancer [NCT00079170] | | 0 participants | Interventional | 2004-01-31 | Completed |
| 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 3 | 0 participants | Interventional | 2001-03-31 | Completed |
| An Open-label, Phase I, Dose-escalation Study of ABR-217620 in Combination With Docetaxel in Patients With Advanced Non-small Cell Lung Cancer (NSCLC) [NCT00132379] | Phase 1 | 13 participants (Actual) | Interventional | 2005-11-30 | Completed |
| A Phase II Clinical Trial of Taxotere, Emcyt and Thalidomide (TET) for the Treatment of Hormone-Refractory Prostate Cancer [NCT00046826] | Phase 2 | 0 participants | Interventional | 2001-09-30 | Completed |
| A Randomized Phase III Trial Comparing FEC-Chemotherapy vs. EC-Doc-Chemotherapy in Patients With Primary Breast Cancer [NCT00047099] | Phase 3 | 446 participants (Anticipated) | Interventional | 2001-08-31 | Completed |
| 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 3 | 263 participants (Actual) | Interventional | 2002-05-31 | Completed |
| Phase 1-2a Dose-Ranging Study of TLK286 in Combination With Docetaxel (Taxotere) in Platinum-Resistant Non-Small Cell Lung Cancer [NCT00047801] | Phase 1/Phase 2 | 28 participants | Interventional | 2002-10-31 | Completed |
| A Randomized, Double-blind, Multicenter, Phase II Study to Assess the Safety, Tolerability, and Efficacy of ZD6474 in Combination With Docetaxel (TAXOTERE™) in Subjects With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC) After Failure o [NCT00047840] | Phase 2 | 129 participants | Interventional | 2002-10-31 | Completed |
| Phase III Study of Docetaxel Vs Vinorelbine in Elderly Patients With Advanced Non-Small Cell Lung Cancer [NCT00148291] | Phase 3 | 180 participants | Interventional | 1999-06-30 | Completed |
| A Phase I Study of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, OSI-774, in Combination With Docetaxel and Radiation in Locally Advanced Squamous Cell Cancer of the Head and Neck [NCT00049283] | Phase 1 | 30 participants (Actual) | Interventional | 2002-09-30 | Completed |
| Impact of Early FDG-PET Directed Intervention on Preoperative Therapy for Locally Advanced Gastric Cancer: A Random Assignment Phase II Study [NCT02485834] | Phase 2 | 5 participants (Actual) | Interventional | 2015-08-31 | Terminated(stopped due to Poor accrual) |
| A Phase 2, Multi-Center Trial of ZD1839 (IRESSA) in Combination With Docetaxel as First-Line Treatment in Patients With Advanced Breast Cancer [NCT00052169] | Phase 2 | 33 participants (Actual) | Interventional | 2003-01-31 | Completed |
| A Phase II Trial of One-Cycle Induction Chemotherapy Followed by Pulsed Docetaxel and Concurrent Radiation for Non-Small Cell Lung Cancer [NCT00167401] | Phase 2 | 0 participants | Interventional | 2002-02-28 | Completed |
| Randomized And Multicentric Opened Phase III Study Evaluating The Concomitant Administration Of Docetaxel 75MG/M2 and Epirubicine 75MG/M2 Versus FEC 100 In Non Metastatic With Positive Lymphatic Nodes Breast Cancer Subjects, And The Sequential Addition Of [NCT00054587] | Phase 3 | 3,010 participants (Actual) | Interventional | 2001-06-30 | Completed |
| Phase I Study of a Novel Schedule of Capecitabine and Docetaxel in Patients With Advanced Solid Tumors [NCT00169000] | Phase 1 | 12 participants (Actual) | Interventional | 2003-01-31 | Completed |
| An Intergroup Phase III Trial to Evaluate the Activity of Docetaxel, Given Either Sequentially or in Combination With Doxorubicin, Followed by CMF, in Comparison to Doxorubicin Alone or in Combination With Cyclophosphamide, Followed by CMF, in the Adjuvan [NCT00174655] | Phase 3 | 2,887 participants (Actual) | Interventional | 1998-06-30 | Completed |
| A Two Arm Phase II Study Comparing Docetaxel/Cisplatin Induction Therapy Followed By Concurrent Chemoradiotherapy Versus Concurrent Chemoradiotherapy Followed By Consolidation Docetaxel/Cisplatin in Patients With Locally Advanced Unresectable NSCLC (Stage [NCT00174772] | Phase 2 | 72 participants (Actual) | Interventional | 2004-03-31 | Completed |
| A Phase II Trial of 13-Cis Retinoic Acid, Alpha Interferon, Taxotere, and Estramustine (R.I.T.E.) for the Treatment of Hormone Refractory Prostate Cancer [NCT00176527] | Phase 2 | 40 participants (Anticipated) | Interventional | 2002-11-30 | Terminated(stopped due to accrual goal met) |
| Evaluation of Response Rate to Pre-Operative Docetaxel + Herceptin Study Part A and Docetaxel Study Part B in Locally Advanced Breast Cancer Patients, Stratified by HER2-Status Trial - PHASE II [(Herceptin Docetaxel Neoadjuvant) HEDON] [NCT00398489] | Phase 2 | 94 participants (Anticipated) | Interventional | 2006-10-31 | Active, not recruiting |
| Phase I Trial of Liposomal Doxorubicin (Doxil) and Weekly Docetaxel (Taxotere) [NCT00183742] | Phase 1 | 35 participants | Interventional | 2000-12-31 | Completed |
| A Phase II Study of Bortezomib (Velcade®, PS-341) and Docetaxel for Patients With Hormone Refractory Prostate Cancer [NCT00183937] | Phase 2 | 15 participants (Actual) | Interventional | 2005-04-30 | Completed |
| Phase II Study Of Weekly Docetaxel In Patients With Advanced Epidermoid Carcinoma Of The Penis [NCT00058448] | Phase 2 | 1 participants (Actual) | Interventional | 2004-10-31 | Terminated(stopped due to Study terminated due to poor patient recruitment.) |
| Phase II Study of Oxaliplatin and Taxotere in Metastatic Bladder Cancer [NCT00186277] | Phase 2 | 10 participants (Actual) | Interventional | 2003-12-31 | Completed |
| Phase III Trial of Doxorubicin /Cyclophosphamide (AC), Docetaxel (D), and Alternating AC and D (AC-D) as Front-line Chemotherapy for Metastatic Breast Cancer: Japan Clinical Oncology Group Trial (JCOG9802) [NCT00190489] | Phase 3 | 450 participants | Interventional | 1999-01-31 | Completed |
| A Phase II Trial of Epirubicin/Docetaxel in the First-Line Treatment of Patients With Metastatic Breast Cancer [NCT00193024] | Phase 2 | 90 participants | Interventional | 2001-09-30 | Terminated |
| A Phase I Study of Topotecan in Combination With Docetaxel in Patients With Refractory and/or Advanced Solid Tumors [NCT00193570] | Phase 1 | 20 participants | Interventional | 2002-02-28 | Completed |
| Taxotere Plus Weekly Navelbine and G-CSF: A Phase II Study in Stage IV Breast Cancer [NCT00194740] | Phase 2 | 48 participants (Actual) | Interventional | 1997-11-30 | Completed |
| A Phase II Study of ZD1839 (Iressa), Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor, in Combination With Docetaxel in Patients With Recurrent or Metastatic Advanced Non-Small Cell Lung Cancer [NCT00048087] | Phase 2 | 0 participants (Actual) | Interventional | 2002-08-31 | Withdrawn(stopped due to Slow accrual.) |
| Adjuvant Chemo-RT With Cisplatin (NSC-119875) and Docetaxel (NSC-628503) After Complete Resection of Locally Advanced (Stage III and IV) Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT00084435] | Phase 2 | 0 participants (Actual) | Interventional | 2005-07-31 | Withdrawn(stopped due to Poor accrual and suspension of head and neck committee) |
| A Phase I Dose Escalation of ZD1839 (Iressa®) (Days 1 and 2) and Docetaxel (Day 3) Every 3 Weeks in Patients With an Advanced Solid Tumor [NCT00084786] | Phase 1 | 0 participants | Interventional | 2004-03-31 | Completed |
| Crossover From Docetaxel and Placebo to Docetaxel and Imatinib in Patients With Androgen-Independent Prostate Cancer With Bone Metastases: Extension Trial to ID03-0008 [NCT00084825] | Phase 2 | 23 participants (Actual) | Interventional | 2003-05-31 | Completed |
| A Phase II Evaluation of Weekly Docetaxel (NSC #628503) in the Treatment of Recurrent or Persistent Endometrial Carcinoma [NCT00085332] | Phase 2 | 0 participants | Interventional | 2004-07-31 | Completed |
| Neoadjuvant Chemoradiotherapy (Gemcitabine/Cisplatin and Taxotere) With or Without Co-Administration of ZD 1839 (Iressa) for Stage IIIA (N2) and Selective Stage IIIB Non-Small Cell Lung Cancer: Phase I-II Study [NCT00062270] | Phase 1/Phase 2 | 0 participants | Interventional | 2003-05-31 | Completed |
| A Dose Escalating (Phase I) Study Looking at the Biomodulation of Capecitabine by Docetaxel and Gemcitabine in Patients With Advanced Pancreas Cancer [NCT00320749] | Phase 1 | 21 participants (Actual) | Interventional | 2005-12-31 | Completed |
| 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 1 | 350 participants (Actual) | Interventional | 2013-11-15 | Active, not recruiting |
| A Phase II Study of Neo-adjuvant Chemotherapy in Locally Advanced Gastric Cancer [NCT00414271] | Phase 2 | 18 participants (Actual) | Interventional | 2006-01-31 | Completed |
| A Phase II Clinical Trial of Bevacizumab Beginning Concurrently With a Sequential Regimen of Doxorubicin and Cyclophosphamide Followed by Docetaxel and Capecitabine as Neoadjuvant Therapy Followed by Postoperative Bevacizumab Alone for Women With Locally [NCT00365417] | Phase 2 | 45 participants (Actual) | Interventional | 2006-08-31 | Completed |
| PHASE II TRIAL WITH DOCETAXEL IN PATIENTS WITH RELAPSING GERM CELL CANCER [NCT00002903] | Phase 2 | 25 participants (Anticipated) | Interventional | 1995-07-31 | Completed |
| A Randomized Phase II Study of Neoadjuvant PD-1 Blockade Alone or Plus TPF Induction Chemotherapy for Resectable Local Advanced Oral Squamous Cell Carcinoma [NCT04649476] | Phase 2 | 68 participants (Actual) | Interventional | 2021-03-22 | Active, not recruiting |
| Phase II Trial of Weekly Docetaxel (Taxotere) Vs. Weekly Docetaxel in Combination With ZD1839 (Iressa®) As Consolidation Therapy For Metastatic Urothelial Cancer Following Maximal Response To Multi-Agent Chemotherapy [NCT00479089] | Phase 2 | 50 participants (Actual) | Interventional | 2004-02-29 | Terminated(stopped due to Study halted due to drug sponsor decision to not continue.) |
| Phase II Study of Imatinib Mesylate and Docetaxel in Patients With Metastatic or Recurrent Head and Neck Squamous Cell Cancer [NCT00485485] | Phase 2 | 7 participants (Actual) | Interventional | 2007-01-31 | Completed |
| A Phase 2 Randomized Open-label Study of Erlotinib Plus Tivantinib (ARQ 197) Versus Single Agent Chemotherapy in Previously Treated KRAS Mutation Positive Subjects With Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT01395758] | Phase 2 | 96 participants (Actual) | Interventional | 2011-07-31 | Completed |
| Differential Gene Regulation During Neoadjuvant Therapy Trial of Epirubicin/Cyclophosphamide (EC) vs Docetaxel/Capecitabine (DX) Regimens in Patients With Large ER-positive and ER-negative Breast Cancers: A Randomized Phase II Trial. [NCT01869192] | Phase 2 | 72 participants (Actual) | Interventional | 2003-03-05 | Completed |
| 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 2 | 28 participants (Anticipated) | Interventional | 2023-05-20 | Recruiting |
| High-dose Chemotherapy for Poor-Prognosis Relapsed Germ-Cell Tumors [NCT00936936] | Phase 2 | 64 participants (Actual) | Interventional | 2009-06-02 | Active, not 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 3 | 275 participants (Actual) | Interventional | 2007-05-31 | Completed |
| 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 2 | 112 participants (Actual) | Interventional | 2007-12-31 | Completed |
| A Phase II Study of Modified Docetaxel, Cisplatin, and Fluorouracil (mDCF) in Patients With Unresectable or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma [NCT00515411] | Phase 2 | 111 participants (Actual) | Interventional | 2006-10-23 | Completed |
| A Randomized Phase 2 Study of Abemaciclib (LY2835219) Versus Docetaxel in Patients With Stage IV Squamous Non-Small Cell Lung Cancer Previously Treated With Platinum-Based Chemotherapy [NCT02450539] | Phase 2 | 159 participants (Actual) | Interventional | 2015-08-06 | Completed |
| Prospective Validation Trial of Taxane Therapy (Docetaxel or Weekly Paclitaxel) and Risk of Chemotherapy-Induced Peripheral Neuropathy in African American Women [NCT04001829] | Phase 2 | 249 participants (Actual) | Interventional | 2019-08-09 | Active, not recruiting |
| A Phase III, Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Efficacy and Safety of Pertuzumab+Herceptin+Docetaxel Versus Placebo+Herceptin+Docetaxel in Previously Untreated HER2-Positive Metastatic Breast Cancer [NCT02896855] | Phase 3 | 243 participants (Actual) | Interventional | 2016-09-13 | Completed |
| A Phase II Trial of Avastin, Docetaxel and Androgen Deprivation Followed by Continued Avastin and Androgen Deprivation for Men With a Rising Prostate Specific Antigen (PSA) After Local Therapy [NCT00658697] | Phase 2 | 42 participants (Actual) | Interventional | 2008-06-30 | Completed |
| 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 2 | 53 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Phase II Study to Evaluate the Efficacy and Toxicity of Multimodality Treatment With Induction Taxotere/Cisplatin?5-FU (TPF) Chemotherapy Followed by Concomitant Cetuximab and Radiation Therapy in Patients With Locally Advanced Squamous Cell Carcinoma of [NCT00721513] | Phase 2 | 20 participants (Actual) | Interventional | 2008-09-30 | Completed |
| A Phase III,Randomized,Multicenter,Double-blind Clinical Trail to Evaluate the Efficacy,Safety and Immunogenicity of the Combination of TQ-B211 Plus Docetaxel Versus Herceptin® Plus Docetaxel as First-line Treatment in Patients With HER2-positive MBC. [NCT04385563] | Phase 3 | 338 participants (Anticipated) | Interventional | 2018-11-11 | 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 2 | 240 participants (Anticipated) | Interventional | 2023-02-09 | Recruiting |
| A Phase II Trial of AK104 in Combination With Docetaxel in Subjects With Advanced Non-Small Cell Lung Cancer and Progressive Disease After Platinum Doublet Chemotherapy and Treatment With One Prior Anti-PD-1/PD-L1 Monoclonal Antibody (mAb) [NCT05215067] | Phase 2 | 40 participants (Anticipated) | Interventional | 2022-03-09 | Recruiting |
| Multicenter Exploratory Trial of the Safety and Efficacy of Adjuvant Docetaxel and Carboplatin in Patients With Resected Non-small Cell Lung Cancer [NCT00883675] | Phase 4 | 133 participants (Actual) | Interventional | 2009-05-31 | Completed |
| A Phase II Study of Adjuvant Treatment With Cisplatin-based Chemotherapy Plus Concomitant Atezolizumab in Patients With Stage I (Tumors ≥ 4cm), IIA, IIB, and Select Stage III [Any T1-3 N1-2 and T4N0-2] Resected Non-small Cell Lung Cancer (NSCLC) and the C [NCT04367311] | Phase 2 | 100 participants (Anticipated) | Interventional | 2020-05-22 | Recruiting |
| 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 2 | 101 participants (Actual) | Interventional | 2015-07-31 | Completed |
| Antiangiogenic Therapy or Chemotherapy Combined With PD-1 Inhibitor Versus Standard Chemotherapy for PD-1 Inhibitor Refractory R/M NPC [NCT05549466] | Phase 2 | 84 participants (Anticipated) | Interventional | 2022-10-08 | Recruiting |
| 4CAST: A Phase 1b Dose Exploration and Dose Expansion, Open-label, Single-centre Study Evaluating the Safety and Efficacy of INO-464 in Combination With Chemotherapy in Patients With metASTatic Breast Cancer [NCT04947189] | Phase 1/Phase 2 | 65 participants (Anticipated) | Interventional | 2022-11-01 | Recruiting |
| Phase I Trial Evaluating the Safety of Durvalumab in Combination With Docetaxel, Cisplatin and 5-FU in Induction for Locally Advanced Head and Neck Squamous Cell Carcinoma [NCT02997332] | Phase 1 | 36 participants (Anticipated) | Interventional | 2017-03-30 | Recruiting |
| A Phase III Trial Comparing Docetaxel Every Third Week to Biweekly Docetaxel Monotherapy in Metastatic Hormone Refractory Prostate Cancer Patients - PROSTY Trial [NCT00255606] | Phase 3 | 360 participants (Anticipated) | Interventional | 2005-08-31 | Completed |
| Randomized Phase II Study Evaluating the Efficacy of Gemcitabine Versus the Gemcitabine/Docetaxel Combination as Second Line Treatment in Metastatic or Relapsed and Inoperable Uterine or Soft Tissue Leiomyosarcomas [NCT00227669] | Phase 2 | 90 participants (Actual) | Interventional | 2005-10-31 | Completed |
| Phase II Trial Assessing the Impact on Instrumental and Daily Living Autonomy of a Chemotherapy Regimen With Bi-Weekly Docetaxel in the Treatment of Metastatic or Locally Advanced Non-Small Cell Lung Cancer in Patients Over the Age of 70 [NCT00227708] | Phase 2 | 58 participants (Anticipated) | Interventional | 2005-06-30 | Completed |
| Phase II Trial of Docetaxel Plus Imatinib Mesylate in Metastatic Breast Cancer [NCT00193180] | Phase 2 | 37 participants (Actual) | Interventional | 2005-05-31 | Completed |
| Randomized Trial of Gemcitabine Plus Docetaxel vs. Docetaxel Plus Capecitabine in Metastatic Breast Cancer in 1st and 2nd [NCT00191152] | Phase 3 | 475 participants (Actual) | Interventional | 2002-02-28 | Completed |
| A Phase IIb Randomised Clinical Trial of the Tolerability, Safety and Efficacy of Adjuvant Docetaxel-Zoledronic Acid After Prostatectomy for High-risk Early Prostate Cancer (AD-ZAP). [NCT00258765] | Phase 2 | 1 participants (Actual) | Interventional | 2006-05-31 | Terminated(stopped due to Poor recruitment & not feasible to continue) |
| Phase I & Biological Study of Etanercept & Weekly Docetaxel in Patients With Advanced Solid Tumors [NCT00201812] | Phase 1 | 27 participants (Actual) | Interventional | 2000-11-30 | Completed |
| Phase I Study of the Combination of Zoledronic Acid and Docetaxel in Patients With Hormone Refractory Metastatic Prostate Cancer [NCT00415779] | Phase 1 | 36 participants (Anticipated) | Interventional | 2006-07-31 | Completed |
| A Randomised Phase II Study of Two Dose Schedules of PI-88 in Combination With Docetaxel in Patients With Androgen-independent Prostate Cancer [NCT00268593] | Phase 2 | 48 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Multicenter Phase II Study of Taxotere (Docetaxel) Administered Weekly or Every Three Weeks in Combination With Prednisone as Second Line Chemotherapy in Patients With Hormone Refractory Prostate Cancer (HRPC) [NCT00268710] | Phase 2 | 0 participants | Interventional | 2004-02-29 | Completed |
| Phase II Study of Calcitriol-Enhanced Docetaxel in Patients With Previously Untreated Metastatic or Locally Advanced Pancreatic Cancer [NCT00238199] | Phase 2 | 25 participants (Actual) | Interventional | 2002-06-30 | Completed |
| A Phase I Study Evaluating the Combination Afatinib With Docetaxel and Cisplatin (TPA) in Induction Chemotherapy in Locally Advanced Squamous Cell Carcinoma of the Upper Aerodigestive Tract [NCT02216617] | Phase 1 | 8 participants (Actual) | Interventional | 2014-08-06 | Completed |
| A Phase II Pilot Study of Combination of Irinotecan and Cisplatin in Docetaxel/Cisplatin-Responsive Advanced Non-Small Cell Lung Cancer [NCT00263016] | Phase 2 | 50 participants (Anticipated) | Interventional | 2005-05-31 | Terminated(stopped due to Slow recruitment) |
| A Phase II Study to Evaluate the Safety and Efficacy of the Combination of ZD1839 (IRESSA™), Docetaxel and Cisplatin in Subjects With Recurrent and/or Metastatic Head and Neck Cancer [NCT00242762] | Phase 2 | 36 participants | Interventional | 2003-07-31 | Completed |
| Phase II Trial of Neoadjuvant Docetaxel and ZD 1839 (Iressa) Followed by Radical Prostatectomy in Patients With High Risk, Locally Advanced Prostate Cancer [NCT00242918] | Phase 2 | 29 participants | Interventional | 2003-05-31 | Completed |
| Multi-Institutional Phase II Study of Weekly Docetaxel and Concurrent Radiotherapy for Laryngeal and Hypopharyngeal Cancer in the Group of Elderly and/or Patients With Medical Illness [NCT00243113] | Phase 2 | 50 participants (Anticipated) | Interventional | 2004-06-30 | Completed |
| A Randomized Phase III Multicenter Trial of Neoadjuvant Docetaxel (Taxotere®) Plus Cisplatin and 5-Fluorouracil (TPF) Versus Neoadjuvant Cisplatin Plus 5-Fluorouracil Followed by Concomitant Chemoradiotherapy to Improve the Overall Survival and Progressio [NCT00273546] | Phase 3 | 500 participants (Actual) | Interventional | 1999-05-31 | Completed |
| A Randomized Cost-minimization Trial Comparing Pemetrexed (Alimta®) Versus Docetaxel (Taxotere®) as Second Line Treatment in Advanced Non Small Cell Lung Cancer (NSCLC): Study 05-06 of Groupe Français de Pneumo-Cancérologie (GFPC). [NCT00284778] | Phase 3 | 150 participants (Anticipated) | Interventional | 2006-02-28 | Completed |
| A Multicentre, Randomised, Double-Blind, Non-Comparative Phase II Trial Of ZD1839 (Iressa™) And Placebo In Combination With Chemotherapy With Docetaxel As First-Line Treatment In Patients With Metastatic Breast Cancer [NCT00247481] | Phase 2 | 77 participants | Interventional | 2002-09-30 | Completed |
| Phase II Study of Weekly Carboplatin and Taxotere in Platinum Sensitive Relapsed Ovarian or Tubal or Primary Peritoneal Cancers [NCT00247988] | Phase 2 | 38 participants | Interventional | 2003-10-31 | Terminated(stopped due to Regulatory issues(trial temporarily suspended December 28, 2005. Permanently suspended January 19, 2007. Institutional Reveiw Board informed April 18, 2007) |
| A Phase II Study of Taxotere and Gemcitabine for Stages III-B and IV Non-Small Cell Lung Cancer [NCT00278460] | Phase 2 | 49 participants (Actual) | Interventional | 2000-11-30 | Completed |
| Open Label, Randomised, Multicenter Phase III Study of Adjuvant Chemotherapy in Radically Resected Adenocarcinoma of the Stomach or Gastroesophageal Junction: Comparison of a Sequential Treatment (CPT-11+5-FU/LV --> TXT+CDDP) Versus a 5-FU/LV Regimen [NCT01640782] | Phase 3 | 1,100 participants (Actual) | Interventional | 2005-02-28 | Completed |
| "Phase II Study of PET Guided Neoadjuvant Chemotherapy (NAC) and Oncotype Guided Hormonal Therapy of Breast Cancer" [NCT01641406] | Phase 2 | 60 participants (Anticipated) | Interventional | 2011-03-31 | Recruiting |
| Phase IV Study of Safety and Efficacy of Docetaxel in Combination With Prednisone in Advanced Hormone Refractory Prostate Cancer Treatment [NCT00280098] | Phase 4 | 30 participants (Anticipated) | Interventional | 2006-01-31 | Completed |
| A Multicentre, Randomised, Open-Label, Parallel-Group, Phase III Post-Marketing Clinical Study to Compare the Overall Survival Between Gefitinib and Docetaxel in Patients With Advanced or Metastatic (Stage IIIB/IV), or Recurrent Non-Small Cell Lung Cancer [NCT00252707] | Phase 3 | 484 participants (Anticipated) | Interventional | 2003-09-30 | Completed |
| A Phase II Study of Bi-Weekly Docetaxel Plus 24-Hour Infusion of High-Dose 5-Fluorouracil and Leucovorin(HDFL)for Inoperable Advanced or Metastatic Gastric Cancer [NCT00270543] | Phase 2 | 54 participants (Anticipated) | Interventional | | Not yet recruiting |
| A Randomized Phase II Study of Weekly Docetaxel Plus Cisplatin Followed by Gemcitabine vs. Gemcitabine Plus Cisplatin Followed by Weekly Docetaxel in the Treatment of Advanced Non-Small Cell Lung Cancer [NCT00270582] | Phase 2 | 58 participants (Anticipated) | Interventional | 2005-11-30 | Recruiting |
| A Phase II Trial of Capecitabine and Docetaxel in the Treatment of Advanced and Recurrent Cervical Cancer [NCT00257348] | Phase 2 | 5 participants (Actual) | Interventional | 2004-03-31 | Completed |
| A Two Arm Phase II Study Assessing Docetaxel/Cisplatin Induction Therapy Followed by Concurrent Chemoradiotherapy or Concurrent Chemoradiotherapy Followed by Consolidation Docetaxel/Cisplatin in Patients With Locally Advanced Unresectable NSCLC (Stage III [NCT00271323] | Phase 2 | 14 participants (Actual) | Interventional | 2005-05-31 | Terminated |
| Phase II Trial of Capecitabine (Xeloda) and Weekly Docetaxel (Taxotere) in Metastatic Androgen Independent Prostate Carcinoma [NCT00258284] | Phase 2 | 30 participants (Actual) | Interventional | 2003-08-31 | Completed |
| 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 1 | 54 participants (Anticipated) | Interventional | 2012-06-30 | Suspended(stopped due to Study suspended prior to enrollment) |
| Randomized Phase II Trial of Two Sequential Schedules of Docetaxel and Cisplatin Followed by Gemcitabine in Patients With Advanced Non-small-cell Lung Cancer. [NCT00424853] | Phase 2 | 88 participants (Actual) | Interventional | 2005-05-31 | Completed |
| An Open, Randomized, Multicentre, Phase II Pilot Study of Docetaxel and Cisplatin in the Adjuvant Treatment of Non-Small Cell Lung Cancer (NSCLC) Stage I-II [NCT00293085] | Phase 2 | 37 participants (Actual) | Interventional | 2001-12-31 | Completed |
| A Phase I/II Trial: Docetaxel, Irinotecan, and Carboplatin in the Treatment of Extensive Stage Small Cell Lung Carcinoma [NCT00264134] | Phase 1/Phase 2 | 40 participants | Interventional | 2003-06-30 | Terminated |
| A Phase II Study of Docetaxel Before Medical Castration With Degarelix in Patients With Newly Diagnosed Metastatic Prostatic Adenocarcinoma. [NCT03069937] | Phase 2 | 52 participants (Actual) | Interventional | 2017-03-01 | Active, not recruiting |
| A Multicenter Randomized Phase II Trial in NSCLC Stage IV and IIIB (T4 With Pleural Effusion) in Elderly Independent Patients the Schedule Docetaxel / Gemcitabine First Line Following by Erlotinib When Progression Versus Erlotinib First Line Following by/ [NCT00418704] | | 100 participants (Actual) | Observational | 2006-05-31 | Completed |
| A Phase 3, Randomized, Open-Label Study Evaluating DN-101 in Combination With Docetaxel in Androgen-Independent Prostate Cancer (AIPC) (ASCENT-2) [NCT00273338] | Phase 3 | 1,200 participants (Anticipated) | Interventional | 2006-01-31 | Terminated(stopped due to DSMB) |
| Phase II Randomized Study Evaluting the Effect of Celecoxib as Maintenance Treatment of Stage IIIb Non-Small Cell Lung Cancer That Reponded or is Stable After Radiochemotherapy [NCT00274898] | Phase 2 | 80 participants (Anticipated) | Interventional | 2004-05-31 | Active, not recruiting |
| A Pilot Study to Evaluate The Effects of Neoadjuvant AZD2171, a VEGF Receptor Tyrosine Kinase Inhibitor With Docetaxel, Doxorubicin, and Cyclophosphamide Chemotherapy in Previously Untreated Locally Advanced Breast Cancer [NCT00310089] | | 33 participants (Anticipated) | Interventional | 2006-01-31 | Completed |
| A Phase II Trial of Docetaxel/Prednisone in Combination With Sargramostim as Treatment for Hormone-refractory Prostate Cancer [NCT00313482] | Phase 2 | 35 participants (Actual) | Interventional | 2006-04-30 | Terminated(stopped due to Low accrual) |
| A Phase III Study of Docetaxel and S-1 Versus S-1 in the Treatment of Advanced Gastric Cancer [NCT00287768] | Phase 3 | 628 participants (Anticipated) | Interventional | 2006-03-31 | Completed |
| Phase I Study of Metronomic Daily Dosing of Docetaxel in Women With Progressive or Recurrent Gynecologic Cancer [NCT00287885] | Phase 1 | 18 participants (Actual) | Interventional | 2004-03-31 | Completed |
| A Randomized Phase III Study Exploring the Efficacy of Capecitabine Given Concomitantly or in Sequence to EC-Doc With or Without Trastuzumab as Neoadjuvant Treatment of Primary Breast Cancer [NCT00288002] | Phase 3 | 1,500 participants (Anticipated) | Interventional | 2005-01-31 | Completed |
| First-in-human, Open-label, Dose-escalation Trial With Expansion Cohorts to Evaluate Safety of GEN1046 in Subjects With Malignant Solid Tumors [NCT03917381] | Phase 1/Phase 2 | 752 participants (Anticipated) | Interventional | 2019-05-14 | Recruiting |
| A Phase 1/2 Study of Gemcitabine and Docetaxel in Combination With Hydroxychloroquine (Autophagy Inhibitor) in Patients With Recurrent Osteosarcoma [NCT03598595] | Phase 1/Phase 2 | 31 participants (Actual) | Interventional | 2019-01-28 | Active, not recruiting |
| A Randomized Phase II Pilot Trial of Carboplatin Compared to Docetaxel for Patients With Metastatic Genetic Breast Cancer [BRCA Trial] [NCT00321633] | Phase 2 | 148 participants (Anticipated) | Interventional | 2005-09-30 | Completed |
| Phase II Trial With Taxotere and Cisplatin in Non-operable Adrenocortical Carcinoma [NCT00324012] | Phase 2 | 19 participants (Actual) | Interventional | 2006-04-30 | Completed |
| A Multicenter Phase II Open Label Non-Comparative Trial of RP56976 Administered Every Three Weeks in Combination With Daily Prednisolone for Metastatic Hormone Refractory Prostate Cancer [NCT00291005] | Phase 2 | 42 participants | Interventional | 2004-08-31 | Completed |
| A Phase II Randomized Trial Of Surgery Followed By Chemoradiotherapy Plus Cetuximab For Advanced Squamous Cell Carcinoma Of The Head and Neck [NCT00084318] | Phase 2 | 238 participants (Actual) | Interventional | 2004-04-30 | Completed |
| A Randomized Placebo-Controlled Phase Ib/IIa Safety, Tolerability and Efficacy Study of Oral Phenoxodiol in Combination With Docetaxel Versus Docetaxel Alone in Patients With Recurrent Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancer [NCT00303888] | Phase 1 | 31 participants (Actual) | Interventional | 2006-05-31 | Terminated |
| A Phase 1 Trial of Amplimexon® (Imexon, Inj.) Plus Taxotere® (Docetaxel) in Previously Treated Inoperable Stage III and Stage IV Non-Small Cell Lung Cancer (NSCLC), Locally Advanced or Metastatic Previously Treated Breast Cancer or Hormone Refractory Pros [NCT00327288] | Phase 1 | 34 participants (Actual) | Interventional | 2005-10-31 | Completed |
| 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 2 | 88 participants (Actual) | Interventional | 2003-12-31 | Terminated(stopped due to Due to poor accrual) |
| Adjuvant Therapy of Breast Cancer: Impact of Erythropoiesis Stimulating Factors on Event Free Survival High Risk Breast Cancer Treatment [NCT00309920] | | 1,234 participants (Anticipated) | Interventional | 2004-01-31 | Recruiting |
| Prevention of Chemotherapy-induced Menopause by Temporary Ovarian Suppression With Triptorelin Vs. Control in Young Breast Cancer Patients. A Randomized Phase III Multicenter Study [PROMISE] [NCT00311636] | Phase 3 | 280 participants (Anticipated) | Interventional | 2003-09-30 | Completed |
| Docetaxel, Cisplatin and Fluorouracil Combination in the Neoadjuvant Treatment of Locally Advanced Gastric Adenocarcinoma : Phase II Clinical Study [NCT00343239] | Phase 2 | 59 participants (Actual) | Interventional | 2006-06-30 | Completed |
| A Randomized, Controlled, Open Label, Phase III Study Evaluating the Efficacy and Safety of JDQ443 Versus Docetaxel in Previously Treated Subjects With Locally Advanced or Metastatic KRAS G12C Mutant Non-small Cell Lung Cancer [NCT05132075] | Phase 3 | 360 participants (Anticipated) | Interventional | 2022-06-15 | Recruiting |
| A Phase II Clinical Trial of Docetaxel, Oxaliplatin Combination Chemotherapy in Patients With Stage IIIB/IV Non-adenocarcinoma, Non-small Cell Lung Cancer (NSCLC) as Second-line Treatment [NCT01497041] | Phase 2 | 35 participants (Anticipated) | Interventional | 2011-02-28 | Recruiting |
| MINT I Multi- Institutional Neo-adjuvant Therapy MammaPrint Project I [NCT01501487] | Phase 4 | 226 participants (Actual) | Interventional | 2011-10-31 | Completed |
| Comparison of the Effectiveness of Neoadjuvant Chemotherapy and the Outcomes Associated With Chemo-induced Amenorrhea Between Docetaxel Plus Epirubicin, and Docetaxel Plus Epirubicin Plus Cyclophosphamide as Neoadjuvant Chemotherapy for Operable Premenopa [NCT01503905] | | 600 participants (Anticipated) | Interventional | 2011-12-31 | Recruiting |
| Explorative Trial to Investigate Catumaxomab (Anti-EpCAM x Anti-CD3) for Treatment of Peritoneal Carcinomatosis in Patients With Gastric Adenocarcinomas Prior to Gastrectomy [NCT01504256] | Phase 2 | 42 participants (Anticipated) | Interventional | 2011-10-31 | Completed |
| A Phase II Randomized Controlled Trial of Adjuvant Chemotherapy for High Risk Gastric Cancer Patients (IIIb-IIIc) [NCT01618474] | Phase 2 | 100 participants (Anticipated) | Interventional | 2012-05-31 | Enrolling by invitation |
| A Phase III, Open-Label, Prospective, Randomized, Multicenter, Neo-adjuvant Study of Chemotherapy Versus Endocrine Therapy in Premenopausal Patient With Hormone Responsive, HER2 Negative, Lymph Node Positive Breast Cancer [NCT01622361] | Phase 3 | 290 participants (Anticipated) | Interventional | 2012-06-30 | Recruiting |
| [NCT01624025] | Phase 2 | 22 participants (Actual) | Interventional | 2012-06-30 | Completed |
| A Multinational, Randomized, Open-Label Phase III Study of Custirsen (TV-1011/OGX-011) In Combination With Docetaxel Versus Docetaxel As A Second-Line Treatment In Patients With Advanced or Metastatic (Stage IV) Non-Small Cell Lung Cancer [NCT01630733] | Phase 3 | 700 participants (Anticipated) | Interventional | 2012-09-30 | Recruiting |
| Randomized Phase II Trial Using Concomitant Chemoradiation Plus Induction or Consolidation Chemotherapy for Unresectable Stage III Non-small Cell Lung Cancer Patients [NCT01652820] | Phase 2 | 140 participants (Actual) | Interventional | 2001-10-31 | Completed |
| A Phase II Randomized Study of Docetaxel With or Without NINTEDANIB (BIBF-1120) in Patient Receiving a First or Second-line of Chemotherapy for HER Negative Metastatic or Locally Recurrent Breast Cancer [NCT01658462] | Phase 2 | 51 participants (Actual) | Interventional | 2013-05-31 | Completed |
| Boanmycin Hydrochloride for Injection in Combination With Docetaxel for Patients With Advanced Lung Squamous Cell Carcinoma as Salvage Chemotherapy: a Prospective, Randomized, Parallel and Controlled Clinical Trial [NCT01660399] | Phase 2 | 300 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| Randomized, Open Label, Positive Controlled, Multicenter Trial to Evaluate Icotinib as First-line and Maintenance Treatment in EGFR Mutated Patients With Lung Adenocarcinoma [NCT01665417] | Phase 4 | 100 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| 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 2 | 207 participants (Anticipated) | Interventional | 2017-12-21 | Recruiting |
| Comparison the Safety and Efficacy of Epirubicin Plus Cyclophosphamide (EC)Versus Docetaxel Plus Cyclophosphamide (TC) in Lymph Node Negative, ER Positive, Her2 Negative Breast Cancer Patients as Adjuvant Chemotherapy [NCT02549677] | Phase 4 | 294 participants (Actual) | Interventional | 2015-10-31 | Completed |
| 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 2 | 68 participants (Actual) | Interventional | 1999-11-30 | Completed |
| A Randomized, Controlled, Open-label, Multicenter, Phase Ш Clinical Study of the Efficacy and Safety of KN026 in Combination With HB1801 Versus Trastuzumab in Combination With Pertuzumab and Docetaxel in the First-line Treatment of Subjects With HER2-posi [NCT05838066] | Phase 3 | 880 participants (Anticipated) | Interventional | 2023-07-31 | Not yet recruiting |
| A Phase 1b Dose Escalation Trial of PSK®/Placebo With Docetaxel to Treat Metastatic Castration-resistant Prostate Cancer [NCT01685489] | Phase 1 | 0 participants (Actual) | Interventional | 2013-05-31 | Withdrawn(stopped due to funding sequestered) |
| Molecular Imaging for Response Assessment of Bevacizumab + Docetaxel as Neoadjuvant Chemotherapy in Primary Breast Cancer [NCT01690325] | Phase 2 | 21 participants (Actual) | Interventional | 2012-09-30 | Terminated(stopped due to Therapy of HER2+ patients according to protocol was no longer appropriate. Patient enrolment behind planned schedule and challenges of site performance) |
| Neo-/Adjuvant Phase III Trial to Compare Intense Dose-dense Chemotherapy to Tailored Dose-dense Chemotherapy in Patients With High-risk Early Breast Cancer (GAIN-2) [NCT01690702] | Phase 3 | 2,886 participants (Actual) | Interventional | 2012-09-30 | Completed |
| A Phase II Study of Docetaxel and S-1 as First-line Chemotherapy in Patients With Advanced Esophageal Cancer [NCT01693432] | Phase 2 | 37 participants (Anticipated) | Interventional | 2011-11-30 | Recruiting |
| Total Neoadjuvant Therapy for the Treatment of Gastroesophageal Junction (GEJ) and Gastric Cancers: A Pilot Trial [NCT05296005] | Phase 1 | 20 participants (Anticipated) | Interventional | 2022-05-31 | Not 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 2 | 0 participants (Actual) | Interventional | 2021-01-15 | Withdrawn(stopped due to Business objectives have changed) |
| A Clinical Trial of the P-Glycoprotein Antagonist, Tariquidar (XR9576), in Combination With Docetaxel in Patients With Lung, Ovarian, Renal and Cervical Cancer: Analysis of the Interaction Between Tariquidar and Docetaxel [NCT00069160] | Phase 2 | 48 participants (Actual) | Interventional | 2003-09-30 | Completed |
| Evaluation of Docetaxel in Recurrent, Platinum Resistant, Refractory and Paclitaxel Refractory Ovarian Cancer and Primary Peritoneal Carcinoma [NCT00004037] | Phase 2 | 0 participants | Interventional | 1998-06-30 | Terminated |
| The Effectiveness and Safety of Neoadjuvant Pegylated Liposomal Doxorubicin and Docetaxel in Breast Cancer. [NCT03221881] | | 100 participants (Actual) | Interventional | 2015-01-31 | Completed |
| Molecular Markers Predictive Response to Dose Dense Chemotherapy With Epirubicin and Docetaxel in Sequences for Locally Advanced Breast Cancer. [NCT00496795] | Phase 2 | 100 participants (Anticipated) | Interventional | 2007-09-30 | Active, not recruiting |
| Phase II Individualized Therapies Selection Study for Patients With Metastatic Colorectal Carcinoma According to the Genomic Expression Profile in Tumor Samples. [NCT01703910] | Phase 2 | 29 participants (Actual) | Interventional | 2012-11-30 | Completed |
| A Phase 1, Multicenter, Open-Label, Dose Escalation Study of ASP9853 in Combination With Either Docetaxel or Paclitaxel in Subjects With Advanced Non-hematologic Malignancies [NCT01705483] | Phase 1 | 21 participants (Actual) | Interventional | 2012-08-28 | Terminated(stopped due to Based on the results of the Phase 1 data, the company decided not to pursue the development of this drug at this time.) |
| A Randomised Phase II Trial of Epirubicin, Oxaliplatin and Capecitabine (EOX) Versus Docetaxel and Oxaliplatin (ElTax) in the Treatment of Advanced Gastro-oesophageal Cancer [NCT01710592] | Phase 2 | 35 participants (Actual) | Interventional | 2007-05-31 | Completed |
| A Phase II Study of Salvage Docetaxel in Patients With Advanced Urothelial Cancer Failed to Prior Chemotherapy [NCT01711112] | Phase 2 | 31 participants (Actual) | Interventional | 2010-08-31 | Completed |
| A Phase I-II Evaluation of the Safety and Efficacy of the Oral HSP90 Inhibitor Debio 0932 in Combination With Standard of Care in first-and Second-line Therapy of Patients With Stage IIIb or IV Non-small Cell Lung Cancer-the HALO Study (HSP90 Inhibition A [NCT01714037] | Phase 1 | 82 participants (Actual) | Interventional | 2012-08-31 | Terminated |
| [NCT01718626] | Phase 2 | 100 participants (Anticipated) | Interventional | 2012-10-31 | Active, not recruiting |
| Phase I/II Study of the Combination of Docetaxel, Gemcitabine and Pazopanib for Neoadjuvant Treatment of Patients With Operable Soft Tissue Sarcoma [NCT01719302] | Phase 1/Phase 2 | 6 participants (Actual) | Interventional | 2012-10-31 | Completed |
| A Phase III Multicenter, Randomized, Open-label, Active-Controlled Study of SHR-A1811 With or Without Pertuzumab Versus Trastuzumab, Pertuzumab and Docetaxel in HER2-Positive Recurrent or Metastatic Breast Cancer [NCT06057610] | Phase 3 | 864 participants (Anticipated) | Interventional | 2023-10-31 | Not yet recruiting |
| A Phase Ⅱ Randomized Controlled Trial to Compare Chemotherapy Sequenced by EGFR-TKIs and Chemotherapy Combined With EGFR-TKIs for Advanced or Metastatic NSCLC Patients Failed to EGFR-TKIs Therapy [NCT01746277] | Phase 2 | 60 participants (Anticipated) | Interventional | 2012-10-31 | Recruiting |
| Phase II Clinical Trial of Cisplatin,Docetaxel and S-1 as First Line Chemotherapy for Advanced Gastric and Gastroesophageal Junction Cancer [NCT01747707] | Phase 2 | 40 participants (Anticipated) | Interventional | 2012-09-30 | Recruiting |
| Randomised Phase II Pilot Study: Induction Chemotherapy With Docetaxel, Cisplatin and Cetuximab Versus Docetaxel, Cisplatin and 5 FU Followed by Radiotherapy With Cetuximab for Locally Advanced or Not Resectable Carcinoma of the Head and Neck [NCT01884259] | Phase 2 | 100 participants (Actual) | Interventional | 2013-05-31 | Completed |
| A Multi-Institution Study of TGFβ Imprinted, Ex Vivo Expanded Universal Donor NK Cell Infusions as Adoptive Immunotherapy in Combination With Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Pediatric Bone and Soft Tissue [NCT05634369] | Phase 1/Phase 2 | 50 participants (Anticipated) | Interventional | 2022-11-14 | Recruiting |
| A Randomized Phase III Trial of Intravesical BCG veRsus Intravesical Docetaxel and GEmcitabine Treatment in BCG Naïve High Grade Non-Muscle Invasive Bladder Cancer (BRIDGE) [NCT05538663] | Phase 3 | 870 participants (Anticipated) | Interventional | 2023-02-07 | Recruiting |
| 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 2 | 160 participants (Actual) | Interventional | 2022-07-25 | Active, not recruiting |
| A Randomized, Multicenter, Phase Ⅱ/Ш Clinical Study to Evaluate the Efficacy of KN026 in Combination With Chemotherapy in Subjects With HER2 Positive Advanced Unresectable or Metastatic Gastric Cancer (Including Gastro-esophageal Junction Adenocarcinoma) [NCT05427383] | Phase 2/Phase 3 | 286 participants (Anticipated) | Interventional | 2022-04-07 | Recruiting |
| A Phase 1/2, Randomized Study Evaluating Multiple Nivolumab Combination Therapies in Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer (NSCLC) After Failure of Platinum-Based Chemotherapy and Anti-PD-1 (L)1 Immunotherapy [NCT04151563] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2021-04-15 | Withdrawn(stopped due to Business objectives have changed) |
| Phase II Trial of Trastuzumab in Combination With Pertuzumab in Pretreated Patients With Non-small Cell Lung Cancer (NSCLC) Harboring a Her2 Mutation and Receiving Docetaxel [NCT03845270] | Phase 2 | 46 participants (Actual) | Interventional | 2019-05-17 | Completed |
| Phase II Trial of Nivolumab With Chemotherapy as Neoadjuvant Treatment in Inflammatory Breast Cancer (IBC) [NCT03742986] | Phase 2 | 8 participants (Actual) | Interventional | 2019-05-02 | Completed |
| 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 2 | 82 participants (Anticipated) | Interventional | 2019-03-12 | Recruiting |
| An Open-Label, Randomized Phase 3 Study to Evaluate Enfortumab Vedotin vs Chemotherapy in Subjects With Previously Treated Locally Advanced or Metastatic Urothelial Cancer (EV-301) [NCT03474107] | Phase 3 | 608 participants (Actual) | Interventional | 2018-06-27 | Active, not recruiting |
| A Phase Ⅱ Randomized Controlled Trial to Compare Gefitinib With Docetaxel as Second-line Therapy for Advanced or Metastatic Non-squamous NSCLC Patients With Wild-type EGFR [NCT01755923] | Phase 2 | 60 participants (Anticipated) | Interventional | 2012-12-31 | Recruiting |
| Phase II Trial of Neoadjuvant Concurrent Chemoradiation With Weekly Docetaxel/Cisplatin for Resectable IIIA-N2 NSCLC [NCT01771289] | Phase 2 | 50 participants (Anticipated) | Interventional | 2013-01-31 | Recruiting |
| A Phase III, Open-label, Randomized, Controlled Study of Utidelone in Combination With AC Versus Docetaxel in Combination With AC for Neoadjuvant Chemotherapy in Patients With High-risk Early-stage or Locally Advanced HER2-negative Breast Cancer [NCT05673629] | Phase 3 | 552 participants (Anticipated) | Interventional | 2023-05-30 | Recruiting |
| Randomized Double-blind Controlled Clinical Study of Chemotherapy Combined With or Without Traditional Chinese Medicine on Survival Affect of Elderly Patients With Advanced Non-small-cell Lung Cancer [NCT01780181] | | 82 participants (Actual) | Observational | 2012-12-31 | Completed |
| Phase I Study of Afatinib With Postoperative Radiation Therapy for Intermediate and High Risk Squamous Cancer of the Head and Neck (SCCHN) [NCT01783587] | Phase 1 | 38 participants (Anticipated) | Interventional | 2013-02-28 | Completed |
| A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors [NCT05094336] | Phase 1/Phase 2 | 527 participants (Anticipated) | Interventional | 2022-02-01 | Recruiting |
| Phase II Randomized Study of Docetaxel With or Without Low-dose, Short Course Sunitinib in the Treatment of Advanced Solid Tumors [NCT01803503] | Phase 2 | 80 participants (Anticipated) | Interventional | 2013-05-31 | Recruiting |
| An Open-label, Single-arm, Phase II Study to Assess the Efficacy and Safety of Endostar® (Recombinant Human Endostatin Injection) Plus Gemcitabine and Docetaxel in Treatment of Soft Tissue Sarcoma Patients With Pulmonary Metastases [NCT01812018] | Phase 2 | 30 participants (Anticipated) | Interventional | 2012-11-30 | Recruiting |
| A Phase Ib/II, Open-label Study of LJM716 in Combination With BYL719 Compared to Taxane or Irinotecan in Patients With Previously Treated Esophageal Squamous Cell Carcinoma (ESCC) [NCT01822613] | Phase 1 | 48 participants (Actual) | Interventional | 2013-07-26 | Completed |
| Phase 2-3 Study of Silymarin on Cisplatin Induced Nephrotoxicity [NCT01829178] | Phase 2/Phase 3 | 30 participants (Actual) | Interventional | 2013-08-31 | Completed |
| Neoadjuvant Androgen Deprivation Therapy and Chemotherapy Followed by Radical Prostatectomy in Patients With Prostate Cancer [NCT02494713] | Phase 2 | 4 participants (Actual) | Interventional | 2015-10-31 | Terminated(stopped due to slow enrollment; resource re-allocation) |
| Phase II Trial Using Erbitux+ Taxotere With Low Dose Fractionated Radiation for Recurrent Unresectable Locally Advanced Head and Neck Carcinoma [NCT01794845] | Phase 2 | 5 participants (Actual) | Interventional | 2013-06-03 | Terminated(stopped due to Early termination due to lack of efficacy (overall response)) |
| 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 3 | 372 participants (Anticipated) | Interventional | 2021-12-20 | Recruiting |
| A Phase II Randomized Prospective Trial of Docetaxel/Prednisone Versus Docetaxel/Prednisone and Enzalutamide in Castration-Resistant Prostate Cancer (CRPC) Patients Progressing on Enzalutamide [NCT02685267] | Phase 2 | 9 participants (Actual) | Interventional | 2016-02-29 | Terminated |
| A Phase III Clinical Trial Comparing the Combination of Docetaxel Plus Cyclophosphamide to Anthracycline-Based Chemotherapy Regimens for Women With Node-Positive or High-Risk Node-Negative, HER2-Negative Breast Cancer [NCT01547741] | Phase 3 | 1,871 participants (Actual) | Interventional | 2012-04-30 | Active, not recruiting |
| A Phase 1b, Open-Label, Dose-Escalation, Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Orally Administered SM08502 Combined With Hormonal Therapy or Chemotherapy in Subjects With Advanced Solid Tumors [NCT05084859] | Phase 1 | 30 participants (Actual) | Interventional | 2021-11-03 | Active, not recruiting |
| Efficacy and Safety Evaluation of IBI308 Versus Docetaxel in Patients With Advanced or Metastatic Squamous Cell Lung Cancer After Failure of First-line Platinum-based Therapy- a Randomized, Open-label, Multicenter, Parallel, Phase 3 Study (ORIENT-3) [NCT03150875] | Phase 3 | 290 participants (Actual) | Interventional | 2017-09-01 | Completed |
| Phase I/II Trial to Establish the Safety and Preliminary Efficacy of the Combination of Docetaxel, Prednisone, and SOM 230 (Pasireotide) in Metastatic Castrate Resistant Prostate Cancer (CRPC). [NCT01468532] | Phase 1/Phase 2 | 18 participants (Actual) | Interventional | 2011-10-31 | Completed |
| Using PERS(PErsonalized Regimen Selection) Genetic Model Assistant Decision-making System of Neoadjuvant Chemotherapy for Breast Cancer Multicentric, Prospective, Randomized Controlled Phase III Clinical Study [NCT03006614] | Phase 3 | 320 participants (Anticipated) | Interventional | 2016-04-30 | Recruiting |
| A Phase II Clinical Study to Evaluate the Efficacy and Safety of SI-B001 in Combination With Chemotherapy in the Treatment of EGFR WT and ALK WT Recurrent and Metastatic Non-small Cell Lung Cancer [NCT05020457] | Phase 2 | 60 participants (Anticipated) | Interventional | 2021-12-07 | Recruiting |
| An Open-Label Randomized Phase III Trial of BMS-936558 (Nivolumab) Versus Docetaxel in Previously Treated Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) [NCT01673867] | Phase 3 | 582 participants (Actual) | Interventional | 2012-11-02 | Completed |
| Prospective, Open, Multicentre Phase I/II Study to Evaluate the Safety and Efficacy of a Neoadjuvant Radiochemotherapy With Docetaxel and Oxalipaltin in Patients With Adenocarcinoma of the Gastric-oesophageal Junction [NCT00374985] | Phase 1/Phase 2 | 25 participants (Actual) | Interventional | 2005-10-31 | Completed |
| A Multicenter, Single-arm Prospective Phase II Study of Chidamide in Combination With Chemotherapy for Neoadjuvant Treatment of HR-positive/HER2-negative Breast Cancer [NCT05400993] | Phase 2 | 59 participants (Anticipated) | Interventional | 2022-05-23 | Recruiting |
| Induction Chemotherapy Plus Radiotherapy Alone Versus Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: a Phase 3, Multicentre, Randomised Controlled Trial [NCT04414566] | Phase 3 | 562 participants (Anticipated) | Interventional | 2020-06-01 | Not yet recruiting |
| Prospective Study To Validate The Predictive Value Of Mammostrat Score, DDR Score And TLE3 Gene When A Taxane-Based Chemo Agents Or Anthracycline-Based Chemo Agent Is Used In The Neo-Adjuvant Setting [NCT02067416] | Phase 2 | 0 participants (Actual) | Interventional | 2012-07-31 | Withdrawn(stopped due to Funding agent withdrew funding) |
| Randomized Phase II Trial of Neoadjuvant Docetaxel Plus Cisplatin and 5-fluorouracil Followed by Concomitant Chemoradiotherapy and Chemoradiotherapy Alone in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck. [NCT00357149] | Phase 2 | 101 participants (Actual) | Interventional | 2003-01-31 | Completed |
| An Open Label Study to Assess the Effect of a Combination of Avastin and Docetaxel and Sequential Chemotherapy on Pathological Response in Patients With Primary Operable HER2 Negative Breast Cancer [NCT00559754] | Phase 2 | 72 participants (Actual) | Interventional | 2007-12-31 | Completed |
| An Open-label, Randomized Study to Evaluate the Effect of Tarceva, Compared With Alimta (Pemetrexed) or Taxotere (Docetaxel),on Survival in Patients With Advanced, Recurrent or Metastatic Non-small Cell Lung Cancer Who Have Experienced Disease Progression [NCT00556322] | Phase 3 | 424 participants (Actual) | Interventional | 2006-03-31 | Completed |
| Synergy of Pembrolizumab Anti-PD-1 Immunotherapy With Chemotherapy for Poorly Chemo-responsive Thyroid and Salivary Gland Tumors. The iPRIME Study. [NCT03360890] | Phase 2 | 46 participants (Anticipated) | Interventional | 2018-03-26 | Recruiting |
| An Open Label Phase I Safety run-in Trial of Oral Nintedanib Plus Docetaxel Therapy in Japanese Patients With Locally Advanced or Metastatic Adenocarcinoma Subtype Non-small Cell Lung Cancer After Failure of Platinum-based First Line Chemotherapy [NCT02300298] | Phase 1 | 10 participants (Actual) | Interventional | 2014-12-24 | Completed |
| A Pilot Study of Short-term Fasting on Neoadjuvant Chemotherapy in Patients With Newly Diagnosed Breast Cancer (STEFNE Study) [NCT02379585] | Phase 1/Phase 2 | 8 participants (Actual) | Interventional | 2013-01-31 | Terminated(stopped due to PI Decision) |
| Phase II Study of Gemcitabine/Taxotere/Xeloda (GTX) in Combination With Cisplatin in Subjects With Metastatic Pancreatic Cancer [NCT01459614] | Phase 2 | 44 participants (Actual) | Interventional | 2011-11-30 | Completed |
| A Phase 2 Study of GTX-SRS: Neoadjuvant Gemcitabine, Docetaxel, and Capecitabine in Combination With Stereotactic Radiosurgery for Borderline Resectable Pancreatic Cancer [NCT00833859] | Phase 2 | 2 participants (Actual) | Interventional | 2009-03-31 | Terminated(stopped due to Abandoned - Lack of funding after only 2 patients enrolled) |
| A Phase II Trial of Taxotere, Carboplatin and Herceptin in Locally Advanced or Inflammatory Breast Cancer [NCT00118053] | Phase 2 | 5 participants (Actual) | Interventional | 2005-04-30 | Terminated(stopped due to slow accrual) |
| A Phase 2, Multi-Arm Study of Magrolimab in Patients With Solid Tumors [NCT04827576] | Phase 2 | 106 participants (Actual) | Interventional | 2021-10-01 | Active, not recruiting |
| A Phase III, Open-label, Randomised, Multicentre Study of Ceralasertib Plus Durvalumab Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer Without Actionable Genomic Alterations, and Whose Disease Has Progressed On or After [NCT05450692] | Phase 3 | 580 participants (Anticipated) | Interventional | 2022-09-15 | Recruiting |
| A Phase Ⅰb Study Evaluating the Safety, Tolerability and Pharmacokinetics of Pegylated Recombinant Human Endostatin (PEG-ENDO) in Subjects With Advanced / Metastatic Non-small Cell Lung Cancer (NSCLC) or Other Solid Tumors [NCT04413227] | Phase 1 | 30 participants (Anticipated) | Interventional | 2020-04-02 | Recruiting |
| Multiple Centers, Prospective, Phase II Trial of Gemcitabine and Docetaxel Combination Chemotherapy in Patients With Locally Advanced/Metastatic Soft Tissue Sarcoma or Imatinib Mesylate Refractory Advanced/Metastatic Malignant Gastrointestinal Stromal Tum [NCT00359333] | Phase 2 | 58 participants (Actual) | Interventional | 2006-12-31 | Completed |
| 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 2 | 42 participants (Actual) | Interventional | 2011-10-31 | Completed |
| Open-Label, Phase 1/2 Study Evaluating the Relative Bioavailability/Bioequivalence of Different Formulations of Selinexor, the Impact of Hepatic Impairment on Selinexor Pharmacokinetics, and the Tolerability and Antitumor Activity of Selinexor Combination [NCT04256707] | Phase 1/Phase 2 | 120 participants (Anticipated) | Interventional | 2020-01-14 | Recruiting |
| PHASE I/II STUDY OF DOCETAXEL (TAXOTERE) AND ESTRAMUSTINE COMBINATION CHEMOTHERAPY IN PATIENTS WITH PROSTATE CANCER [NCT00002775] | Phase 1/Phase 2 | 37 participants (Anticipated) | Interventional | 1998-02-28 | Active, not recruiting |
| Phase 1b/2 Study Investigating Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of Anti-HER2 Bispecific Antibody ZW25 in Combination With Chemotherapy With/Without Tislelizumab in Patients With Advanced HER2-positive Breast Cancer [NCT04276493] | Phase 1/Phase 2 | 71 participants (Actual) | Interventional | 2020-03-26 | Active, not recruiting |
| Personalized Treatment of Metastatic Castrate Resistant Prostate Cancer Patients According to Circulating Tumor Cells Kinetic During Chemotherapy: A GETUG-AFU 28 Study [NCT03101046] | Phase 2 | 40 participants (Actual) | Interventional | 2018-11-15 | Completed |
| A Randomized Phase II Trial Evaluating the Performance of Genomic Expression Profiles to Direct the Use of Preoperative Chemotherapy for Early Stage Breast Cancer [NCT00636441] | Phase 2 | 56 participants (Actual) | Interventional | 2008-04-30 | Terminated(stopped due to Study terminated due to reproducibility issues with genomics prediction model) |
| PHASE I STUDY OF TAXOTERE IN PATIENTS WITH ADVANCED MALIGNANCIES AND VARYING DEGREES OF LIVER DYSFUNCTION [NCT00002901] | Phase 1 | 0 participants | Interventional | 1996-12-31 | Completed |
| 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 2 | 27 participants (Actual) | Interventional | 2012-12-31 | Completed |
| A Phase II Study of Definitive Therapy for Newly Diagnosed Men With Oligometastatic Prostate Cancer [NCT02716974] | Phase 2 | 26 participants (Actual) | Interventional | 2016-06-30 | Completed |
| A Phase II Study of AB-16B5 Combined With Docetaxel in Previously Treated Subjects With Metastatic Non-Small Cell Lung Cancer (EGIA-002) [NCT04364620] | Phase 2 | 35 participants (Actual) | Interventional | 2021-02-23 | Active, not recruiting |
| Open-label Dose Escalation Phase 1b Trial of a New Micellar Docetaxel Compound in Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) [NCT04629781] | Phase 1 | 11 participants (Actual) | Interventional | 2021-05-28 | Active, not recruiting |
| Phase I Study Evaluating MK6592 in Combination With Docetaxel in Adult Patients With Relapsed or Refractory Advanced Solid Tumors [NCT00359671] | Phase 1 | 38 participants (Anticipated) | Interventional | 2006-12-31 | Terminated |
| A Phase 2 Multicohort Study of Nivolumab in Combination With Docetaxel and Androgen Deprivation Therapy in Metastatic Hormone Sensitive Prostate Cancer Patients With DNA Damage Repair Defects or Inflamed Tumors [NCT04126070] | Phase 2 | 60 participants (Anticipated) | Interventional | 2020-05-11 | Recruiting |
| 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 3 | 444 participants (Actual) | Interventional | 2014-06-25 | Completed |
| A Phase II Trial of Docetaxel/Cisplatin Chemotherapy Followed by Pelvic Radiation Therapy in Patients, With High-risk Endometrial Carcinoma After Staging Surgery [NCT01461746] | Phase 2 | 67 participants (Anticipated) | Interventional | 2011-10-31 | Recruiting |
| Induction Chemotherapy With Taxotere, Cisplatin and 5-Fluorouracil Followed by Concomitant Cetuximab and Radiation for Locoregionally Advanced Squamous Cell Cancer of the Head and Neck: A Phase II Trial [NCT01467115] | Phase 2 | 1 participants (Actual) | Interventional | 2010-03-31 | Completed |
| Phase II Multicentre Open Label Study Evaluating the Efficacy and Safety of Liposomal Doxorubicin, Trastuzumab, Docetaxel as First-line Treatment of Patients With HER2 Positive Metastatic Breast Cancer [NCT00377780] | Phase 2 | 60 participants (Actual) | Interventional | 2006-08-31 | Terminated(stopped due to wothdrawal of sponsor) |
| A Randomized Phase III Evaluation of Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Bevacizumab (NSC #704865) Versus Docetaxel (NSC #628503) and Gemcitabine (NSC #613327) Plus G-CSF With Placebo in the Treatment of Recurrent or Adva [NCT01012297] | Phase 3 | 107 participants (Actual) | Interventional | 2009-11-30 | Terminated(stopped due to The study was targeted to accrue 130 patients, but closed early for futility.) |
| A Phase Ⅲ Study to Evaluate the Efficacy and Safety Of Intravesical Nanoxel®M (Docetaxel-PM) In Bacillius Calmette-Guerin Refractory Non-Muscle Invasive Bladder Cancer [NCT02982395] | Phase 3 | 36 participants (Actual) | Interventional | 2017-01-31 | Terminated |
| Phase II Study of Biweekly Schedule of Docetaxel and Cisplatin in High Risk Patients With Unresectable Non-small Cell Lung Cancer [NCT00995761] | Phase 2 | 48 participants (Actual) | Interventional | 2009-10-31 | Completed |
| An Open Randomized Phase III Trial of Six Cycles of Docetaxel Versus Surveillance After Radical Prostatectomy in High Grade Prostate Cancer Patients With Margin Positive T2 or T3 Tumours [NCT00376792] | Phase 3 | 396 participants (Anticipated) | Interventional | 2005-10-31 | Recruiting |
| A Phase II, Prospective, Single-center, Randomized, Controlled Study to Investigate the Efficacy and Safety of Sintilimab Compared With Docetaxel or Pemetrexed as Second-line Treatment for Patients With Stage IV Nonsquamous Non-small Cell Lung Cancer With [NCT03830411] | Phase 2 | 76 participants (Anticipated) | Interventional | 2019-03-13 | Recruiting |
| Induction Chemotherapy With Docetaxel and Cisplatin Followed by Radiotherapy Alone or Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma [NCT03015727] | Phase 3 | 440 participants (Anticipated) | Interventional | 2016-12-31 | Recruiting |
| A Phase II Study of Adjuvant PALbociclib as an Alternative to CHemotherapy in Elderly patientS With High-risk ER+/HER2- Early Breast Cancer [NCT03609047] | Phase 2 | 366 participants (Anticipated) | Interventional | 2019-06-14 | Active, not recruiting |
| MINDACT (Microarray In Node-Negative and 1 to 3 Positive Lymph Node Disease May Avoid Chemotherapy): A Prospective, Randomized Study Comparing the 70-Gene Signature With the Common Clinical-Pathological Criteria in Selecting Patients for Adjuvant Chemothe [NCT00433589] | Phase 3 | 6,600 participants (Anticipated) | Interventional | 2007-02-28 | Completed |
| 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 2 | 341 participants (Actual) | Interventional | 2015-11-23 | Completed |
| A Randomized, Controlled Clinical Trial Comparing the Efficacy and Safety of a Single Agent Docetaxel 2-weeks Regimen in the Treatment of HER2 Negative Metastatic Breast Cancer to a 3-weeks Regimen [NCT03147963] | Phase 2 | 90 participants (Anticipated) | Interventional | 2015-12-20 | Recruiting |
| A Randomised Phase II/III Trial of Preoperative Chemoradiotherapy Versus Preoperative Chemotherapy for Resectable Gastric Cancer [NCT01924819] | Phase 2/Phase 3 | 574 participants (Actual) | Interventional | 2009-09-30 | Active, not recruiting |
| ONO-4538 Phase III Study A Multicenter, Randomized, Open-label Study in Patients With Esophageal Cancer Refractory or Intolerant to Combination Therapy With Fluoropyrimidine and Platinum-based Drugs [NCT02569242] | Phase 3 | 419 participants (Actual) | Interventional | 2015-12-14 | Completed |
| A Phase 1b/Adaptive Phase 2 Study of Docetaxel With or Without MLN1117 in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer [NCT02393209] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2015-06-03 | Terminated(stopped due to Lack of efficacy in combination.) |
| Phase II, Open Label, Randomized, Biomarker Study of Immune-mediated Mechanism of Action of Neoadjuvant Subcutaneous (SC) Trastuzumab in Patients With Operable or Locally Advanced/Inflammatory HER2-positive Breast Cancer (ImmunHER) [NCT03144947] | Phase 2 | 65 participants (Anticipated) | Interventional | 2016-11-29 | Active, not recruiting |
| A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial of Bavituximab Plus Docetaxel in Patients With Previously Treated Locally Advanced or Metastatic Non-Squamous Non Small-Cell Lung Cancer [NCT01138163] | Phase 2 | 121 participants (Actual) | Interventional | 2010-06-30 | Completed |
| A Phase II, Multicenter, Open-Label Study Of YM155 Plus Docetaxel in Subjects With Stage III (Unresectable) or Stage IV Melanoma [NCT01009775] | Phase 2 | 64 participants (Actual) | Interventional | 2009-11-30 | Completed |
| A Single-arm, Multicenter, Phase Ib/II Clinical Study of Docetaxel for Injection (Albumin-bound) in Combination With Nivolumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) Progressing on or After Platinum-b [NCT05027204] | Phase 1/Phase 2 | 94 participants (Anticipated) | Interventional | 2022-03-04 | Recruiting |
| A Phase I/II Study of Bevacizumab and Erlotinib in Combination With Docetaxel and Prednisone for Patients With Hormone Refractory Prostate Cancer [NCT00996502] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2006-07-31 | Terminated(stopped due to Poor enrollment; PI left the institution) |
| A Prospective Randomized Controlled Study Comparing the Efficacy and Safety of Rezvilutamide+ADT+Docetaxel Versus Rezvilutamide +ADT in the Treatment of Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC) [NCT05983783] | Phase 3 | 200 participants (Anticipated) | Interventional | 2023-08-01 | Recruiting |
| Phase 1/2 Trial Evaluating the Safety and Tolerability of NanoDoce® Injection and Intravesical Instillation in Subjects With Urothelial Carcinoma [NCT03636256] | Phase 1/Phase 2 | 36 participants (Actual) | Interventional | 2019-04-02 | Completed |
| DETECT V / CHEVENDO A Multicenter, Randomized Phase III Study to Compare Chemo- Versus Endocrine Therapy in Combination With Dual HER2-targeted Therapy of Herceptin® (Trastuzumab) and Perjeta® (Pertuzumab) Plus Kisqali® (Ribociclib) in Patients With HER2 [NCT02344472] | Phase 3 | 270 participants (Anticipated) | Interventional | 2015-09-30 | Recruiting |
| A Randomized, Controlled Phase II Study to Compare Preoperative Chemotherapies in Locally Advanced Gastric/Gastroesophageal Cancer [NCT02725424] | Phase 2 | 180 participants (Actual) | Interventional | 2015-08-31 | Completed |
| PHASE III COMPARISON OF TAXOTERE (DOCETAXEL) AND TAXOL (PACLITAXEL) IN PATIENTS WITH ADVANCED BREAST CANCER [NCT00002662] | Phase 3 | 0 participants | Interventional | 1994-08-31 | Completed |
| Neoadjuvant Capecitabine, Oxaliplatin, Docetaxel and Atezolizumab in Non-metastatic, Resectable Gastric and GE-junction Cancer: The PANDA Trial [NCT03448835] | Phase 2 | 20 participants (Anticipated) | Interventional | 2018-03-07 | Recruiting |
| A Study of Combined Treatment of Apatinib With Docetaxel as Post Second-line Therapy in Advanced Non-squamous Non-small Cell Lung Cancer(NSCLC) [NCT03416231] | Phase 2 | 20 participants (Anticipated) | Interventional | 2016-11-30 | Recruiting |
| 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 2 | 30 participants (Anticipated) | Interventional | 1997-10-31 | Completed |
| A Phase II Study of Non-Small Cell Cancer of the Lung Utilizing Low-Dose Weekly Therapy of Taxotere and Carboplatin [NCT00003562] | Phase 2 | 38 participants (Anticipated) | Interventional | 1998-07-31 | Active, not recruiting |
| Phase III Trial of TC Versus TAC in HER2-Negative Early Stage Breast Cancer Patients [NCT00493870] | Phase 3 | 1,961 participants (Actual) | Interventional | 2007-05-29 | Completed |
| Randomized Phase II Trial of Either 5-Fluorouracil, Recombinant Alfa-2a-Interferon and Intravenous Hydroxyurea With Filgrastim Support (FHIG) or Doxorubicin/Docetaxel (Dd) in Patients With Advanced Gastric Cancer [NCT00003172] | Phase 2 | 0 participants | Interventional | 1997-12-31 | Completed |
| A Phase I/II Study of Docetaxel and Epirubicin as First-Line Therapy for Metastatic Breast Cancer [NCT00002866] | Phase 1 | 50 participants (Anticipated) | Interventional | 1996-08-12 | Completed |
| A Phase II Study in Patients With Metastatic or Locally Advanced Breast Cancer to Evaluate the Worth of the Combination of Adriamycin (Doxorubicin), Taxotere (Docetaxel), and Cyclophosphamide (ATC) [NCT00003352] | Phase 2 | 89 participants (Actual) | Interventional | 1998-06-30 | Completed |
| A Randomized Phase II Study of Eribulin/Cyclophosphamide or Docetaxel/Cyclophosphamide as Neoadjuvant Therapy in Locally Advanced HER2-Negative Breast Cancer [NCT01527487] | Phase 2 | 76 participants (Actual) | Interventional | 2012-06-30 | Completed |
| A Phase II Trial of Gemcitabine and Docetaxel in Patients With Unresectable Leiomyosarcoma [NCT00004066] | Phase 2 | 82 participants (Anticipated) | Interventional | 1999-06-30 | Completed |
| A Phase I Open-Label Safety Study of Escalating Doses of Taxotere in Combination With Escalating Doses of GEM231 in Patients With Refractory Solid Tumors [NCT00004864] | Phase 1 | 0 participants | Interventional | 1999-07-31 | Completed |
| 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 2 | 0 participants | Interventional | 1999-10-31 | Completed |
| 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 2 | 236 participants (Anticipated) | Interventional | 2022-12-20 | Recruiting |
| Phase I/II Trial of Amifostine, High-Dose Cisplatin and Docetaxel in Patients With Advanced Lung Cancer [NCT00004264] | Phase 1/Phase 2 | 0 participants | Interventional | 1997-07-31 | Active, not recruiting |
| "A Phase II Trial of Sequential Doublets Chemotherapy in Patients With Locally Advanced or Metastatic Bladder Cancer" [NCT00005086] | Phase 2 | 6 participants (Actual) | Interventional | 1999-08-31 | Completed |
| A Phase II Neoadjuvant Trial of Sequential Doxorubicin and Docetaxel for the Treatment of Stage III Breast Cancer Measuring STAT Activation as a Predictor of Response to Therapy [NCT00005800] | Phase 2 | 45 participants (Actual) | Interventional | 1999-04-30 | Completed |
| The Efficacy and Safety of Postoperative Chemotherapy With Docetaxel Plus Oxaliplatin and Capecitabine Versus Oxaliplatin Plus Capecitabine for Postoperative Pathological Stage IIIB/IIIC Gastric Adenocarcinoma: a Randomised, Phase 3 Trial [NCT04351867] | Phase 3 | 196 participants (Anticipated) | Interventional | 2020-09-30 | Not yet recruiting |
| Prospective Biomarker Analysis of Patients With Metastatic Castration-resistant Prostate Cancer (mCRPC) Undergoing Sequential Treatment With Docetaxel and Enzalutamide [NCT03700099] | Phase 2 | 30 participants (Anticipated) | Interventional | 2019-09-03 | Active, not recruiting |
| Phase III Randomized, Placebo Controlled, Trial of Docetaxel Versus Docetaxel Plus ZD1839 (Iressa, Gefitinib) in Performance Status 2 or Previously Treated Patients With Recurrent or Metastatic Head and Neck Cancer [NCT00088907] | Phase 3 | 270 participants (Actual) | Interventional | 2004-08-31 | Terminated(stopped due to It was unlikely that the primary endpoint would be reached based on the fifth interim analysis results.) |
| A Phase I-II Trial of Dovitinib Plus Docetaxel as Second-line Chemotherapy in Patients With Metastatic or Unresectable Gastric Cancer After Failure of First-line Chemotherapy [NCT01921673] | Phase 1/Phase 2 | 14 participants (Actual) | Interventional | 2013-08-31 | Completed |
| Phase II Study of Gemcitabine and Docetaxel (GEMDOC) Combination in Patients With Previously Treated Recurrent or Metatstatic Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT00248560] | Phase 2 | 36 participants (Actual) | Interventional | 2005-01-31 | Completed |
| An Open-label, Multicenter, Phase I/II Dose Escalation Study of Oral GW572016 in Combination With Docetaxel (Taxotere) Plus Trastuzumab (Herceptin) in Subjects Previously Untreated for ErbB2-overexpressing Metastatic Breast Cancer [NCT00251433] | Phase 1 | 53 participants (Actual) | Interventional | 2005-09-26 | Terminated(stopped due to EGF100161 (NCT00251433) was terminated in Phase I (Phase II expansion portion of the study was never initiated) by sponsor decision.) |
| Phase III Trial to Compare Epirubicin and Cyclophosphamide (EC) Followed by Docetaxel (T) to Epirubicin and Docetaxel (ET) Followed by Capecitabine (X) as Adjuvant Treatment, Node Positive Breast Cancer Patients [NCT00129935] | Phase 3 | 1,384 participants (Actual) | Interventional | 2004-02-29 | Completed |
| A Phase II Study of Induction Chemotherapy Followed by Surgical Treatment in Locally Advanced Oropharyngeal And Supraglotic Cell Carcinoma [NCT02760667] | Phase 2 | 20 participants (Actual) | Interventional | 2015-06-30 | Active, not recruiting |
| 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 3 | 214 participants (Actual) | Interventional | 2018-08-11 | Completed |
| A Single-arm, Phase Ⅱ Clinical Trial of Anlotinib Hydrochloride Combined With Irinotecan or Docetaxel for Second Line Treatment of Nonsensitive Relapsed Small-cell Lung Cancer [NCT04757779] | Phase 2 | 40 participants (Anticipated) | Interventional | 2019-12-30 | Recruiting |
| The Study of Envafolimab Plus Docetaxel in Combination With or Without Trilaciclib Versus Docetaxel in Advanced NSCLC Previously Treated With a PD-1 Inhibitor Combined With Chemotherapy [NCT05910034] | Phase 2 | 132 participants (Anticipated) | Interventional | 2023-07-01 | Not yet recruiting |
| A Phase III Study of Doxorubicin-Cyclophosphamide Therapy Followed by Paclitaxel or Docetaxel Given Weekly or Every 3 Weeks in Patients With Axillary Node-Positive Breast Cancer [NCT00004125] | Phase 3 | 0 participants | Interventional | 1999-11-16 | Completed |
| A Phase IB/II Study of Gemcitabine and Docetaxel in Combination With Pazopanib (Gem/Doce/Pzb) for the Neoadjuvant Treatment of Soft Tissue Sarcoma (STS) [NCT01418001] | Phase 1/Phase 2 | 5 participants (Actual) | Interventional | 2011-08-31 | Terminated(stopped due to Lack of accrual) |
| 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 3 | 341 participants (Anticipated) | Interventional | 2021-03-31 | Not yet 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 2 | 46 participants (Anticipated) | Interventional | 2021-04-02 | Recruiting |
| Neoadjuvant Treatment and Molecular Characterization of Locally Advanced Breast Cancer [NCT00068341] | Phase 2 | 74 participants (Actual) | Interventional | 2003-07-31 | Completed |
| A Multicentre, Randomised Phase II to Compare Epirubicin (E) & Cyclophosphamide (C) Treatment Plus Docetaxel (D) & Trastuzumab vs. E & C Treatment Plus D & Lapatinib in Women With Primary Resectable or Locally Advanced HER2+ Breast Cancer [NCT00841828] | Phase 2 | 102 participants (Actual) | Interventional | 2009-02-28 | Completed |
| Randomized, Multicenter, Phase III, Open-Label Study of Alectinib Versus Pemetrexed or Docetaxel in Anaplastic Lymphoma Kinase-Positive Advanced Non Small Cell Lung Cancer Patients Previously Treated With Platinum-Based Chemotherapy and Crizotinib [NCT02604342] | Phase 3 | 119 participants (Actual) | Interventional | 2015-11-03 | Completed |
| A Phase III Randomized Trial of Gemcitabine (NSC# 613327) Plus Docetaxel (NSC# 628503) Followed by Doxorubicin (NSC# 123127) Versus Observation for Uterus-Limited, High Grade Uterine Leiomyosarcoma [NCT01533207] | Phase 3 | 38 participants (Actual) | Interventional | 2012-06-04 | Terminated |
| A Randomized Controlled Study to Evaluate the Efficacy and Safety of Endocrine Therapy Plus Chemotherapy Versus Chemotherapy Alone as the Neoadjuvant Therapy in the Treatment of ER-positive, HER2-negative Breast Cancer (IIa-IIIc) [NCT02980965] | Phase 3 | 249 participants (Actual) | Interventional | 2013-05-31 | Completed |
| A Phase II Trial of First-Line Therapy With Gemcitabine, Docetaxel, and Cetuximab in Patients With Unresectable Stage III or IV Non-Small Cell Lung Cancer [NCT00193453] | Phase 2 | 69 participants (Actual) | Interventional | 2005-07-31 | Completed |
| A Phase II Trial of Docetaxel, Thalidomide, Prednisone and Bevacizumab in Patients With Androgen-Independent Prostate Cancer [NCT00089609] | Phase 2 | 73 participants (Actual) | Interventional | 2005-04-19 | Completed |
| An Open Label Phase 2 Study to Evaluate the Safety and Efficacy of Lenvatinib With Pembrolizumab or Lenvatinib, Pembrolizumab and FLOT in the Neoadjuvant / Adjuvant Treatment for Patients With Gastric Cancer [NCT04745988] | Phase 2 | 43 participants (Anticipated) | Interventional | 2021-11-11 | Recruiting |
| A Phase 1 First Time in Human Study to Evaluate the Safety, Pharmacokinetics and Immunogenicity of MEDI5083 Alone or in Combination With Durvalumab, Tremelimumab, and/or Docetaxel in Advanced Solid Tumors [NCT03089645] | Phase 1 | 39 participants (Actual) | Interventional | 2017-03-21 | Completed |
| Phase 1b/2 Study of Vorinostat in Combination With Gemcitabine and Docetaxel in Advanced Sarcoma [NCT01879085] | Phase 1/Phase 2 | 37 participants (Actual) | Interventional | 2013-09-24 | Completed |
| Phase II and Coagulation Study of rhuMAb-VEGF With or Without Docetaxel in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma [NCT00066677] | Phase 2 | 32 participants (Actual) | Interventional | 2003-10-31 | Terminated(stopped due to Stopped accordining to early stopping rule for futility) |
| 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 2 | 13 participants (Actual) | Interventional | 2003-03-31 | Terminated(stopped due to low accrual) |
| A Multicenter, Multinational, Randomized, Double-Blind, Phase III Study of IMC-1121B Plus Docetaxel Versus Placebo Plus Docetaxel in Previously Untreated Patients With HER2-Negative, Unresectable, Locally-Recurrent or Metastatic Breast Cancer [NCT00703326] | Phase 3 | 1,144 participants (Actual) | Interventional | 2008-08-06 | Completed |
| A Phase II Trial of Docetaxel, Cetuximab (C225), and Cisplatin Followed by Radiation, Cetuximab, and Cisplatin in Locally Advanced Head and Neck Cancer [NCT00226239] | Phase 2 | 39 participants (Actual) | Interventional | 2005-10-31 | Completed |
| Phase II Evaluation of Ifosfamide Plus Doxorubicin & Filgrastim Versus Gemcitabine Plus Docetaxel & Filgrastim in the Treatment of Localized Poor Prognosis Soft Tissue Sarcoma [NCT00189137] | Phase 2 | 84 participants (Actual) | Interventional | 2004-08-31 | Completed |
| the General Hospital of PLA [NCT03177174] | | 150 participants (Actual) | Interventional | 2017-06-12 | Completed |
| [NCT02402712] | Phase 3 | 418 participants (Actual) | Interventional | 2015-05-06 | Completed |
| A Study to Evaluate the Potential of Concomitant Ramucirumab to Affect the Pharmacokinetics of Docetaxel in Patients With Advanced Malignant Solid Tumors [NCT01567163] | Phase 2 | 22 participants (Actual) | Interventional | 2012-07-31 | Completed |
| Phase II Study of Dose-Dense TC (Docetaxel + Cyclophosphamide) With Pegfilgrastim Support for Adjuvant Therapy of pN0, pN1 or Nx Breast Cancer [NCT01671319] | Phase 2 | 42 participants (Actual) | Interventional | 2011-06-30 | Completed |
| A Multicenter, Open Phase Ib Study to Evaluate the Efficacy and Safety of SCT-I10A in Combination With SCT200 or SCT200 in Combination With Paclitaxel/Docetaxel in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma [NCT05552807] | Phase 1 | 120 participants (Anticipated) | Interventional | 2022-06-15 | Recruiting |
| Feasibility of Assessing Drug Response to Precise Local Injection of Anti-cancer Drugs Using Presage's CIVO Device in Soft Tissue Sarcoma Patients Undergoing Surgery. [NCT03056599] | Phase 1 | 23 participants (Actual) | Interventional | 2016-12-15 | Completed |
| Efficacy and Safety of Pyrotinib in Combination With Neoadjuvant Chemotherapy in Stage II-III HR+/HER2-, HER4 High Expression Breast Cancer Patients: A Phase II, Single-center, Randomized, Double-Blinded, Placebo-Controlled Trial [NCT04872985] | Phase 2 | 140 participants (Anticipated) | Interventional | 2021-04-20 | Recruiting |
| A Randomized Phase III Trial of Erlotinib Versus Docetaxel in Patients With Advanced Squamous Cell Non-small Cell Lung Cancer Who Failed First Line Platinum Based Doublet Chemotherapy Stratified by VeriStrat Good vs VeriStrat Poor [NCT01652469] | Phase 3 | 81 participants (Actual) | Interventional | 2012-08-31 | Completed |
| An Umbrella Study to Evaluate MLN1117 in Combination With Taxanes (Docetaxel or Paclitaxel) and Other Investigational Anticancer Agents for the Treatment of Patients With Previously Treated Advanced and Metastatic Gastric and Gastroesophageal Adenocarcino [NCT02551055] | Phase 1 | 32 participants (Actual) | Interventional | 2015-10-15 | Terminated(stopped due to Business Decision; No Safety Or Efficacy Concerns.) |
| A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum-Containing Chemotherapy [NCT02813785] | Phase 3 | 565 participants (Actual) | Interventional | 2016-07-01 | Completed |
| Weekly Docetaxel, Cisplatin, and Cetuximab (TPC) in Palliative Treatment of Patients With SCCHN [NCT01437449] | Phase 2 | 27 participants (Actual) | Interventional | 2011-10-31 | Completed |
| Using Genetic Polymorphisms of Drug Metabolism and Immunohistochemical Stain to Predict the Efficacy and Toxicity in Patients With Gastric Adenocarcinoma - A Phase II Study [NCT01558011] | Phase 2 | 51 participants (Actual) | Interventional | 2012-03-31 | Terminated(stopped due to The budget issues.) |
| Phase II Randomized Study of Continuing Treatment With Docetaxel Versus Switching to Cabazitaxel After Minor Prostate Specific Antigen Response to Docetaxel in the First Line Treatment of Patients With Castration-Resistant Metastatic Prostate Cancer. [NCT01576029] | Phase 2 | 2 participants (Actual) | Interventional | 2012-08-31 | Completed |
| A Randomized, Phase II Trial Comparing Induction Chemotherapy Gemcitabine Plus Cisplatin With Docetaxel Plus Cisplatin Followed by Concurrent Chemoradiotherapy in Locally Advanced Nasopharyngeal Carcinoma in Northwest China [NCT01596868] | Phase 2 | 60 participants (Anticipated) | Interventional | 2012-05-31 | Completed |
| A Phase II, Randomized, Open-label Platform Trial Utilizing a Master Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC Participants [NCT05553808] | Phase 2 | 105 participants (Actual) | Interventional | 2019-01-24 | Completed |
| A Phase 2 Study of Neoadjuvant Docetaxel, Oxaliplatin, S-1 in Patients With Unresectable Locally Advanced or Distant Metastasis Limited to Lymph Node Gastric Cancer [NCT05184803] | Phase 2 | 63 participants (Anticipated) | Interventional | 2022-03-23 | Recruiting |
| A Phase I Study to Assess the Safety, Tolerability and Pharmacokinetics of Docetaxel Lipid Microsphere for Injection in Cancer Patients Receiving Chemotherapy [NCT01611961] | Phase 1 | 35 participants (Anticipated) | Interventional | 2012-08-31 | Recruiting |
| Phase II Trial of Docetaxel-Cisplatin Neoadjuvant Chemotherapy Followed by Concurrent Radiotherapy With Cetuximab or Weekly Cisplatin in Locally Advanced Nasopharyngeal Carcinoma [NCT01614938] | Phase 2 | 46 participants (Actual) | Interventional | 2010-08-31 | Active, not recruiting |
| 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 2 | 35 participants (Anticipated) | Interventional | 2022-04-20 | Recruiting |
| Perioperative Chemotherapy With FOLFIRINOX Regimen or FLOT Regimen for Resectable Gastric or Esophagogastric Junction Adenocarcinoma (Type II-III): Open-label Randomized Phase 2/3 Trial [NCT04393584] | Phase 2/Phase 3 | 538 participants (Anticipated) | Interventional | 2019-01-29 | Recruiting |
| A Phase III Clinical Trial of Docetaxel Plus Cisplatin Versus Vinorelbine Plus Cisplatin in Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma [NCT02465736] | Phase 3 | 610 participants (Anticipated) | Interventional | 2015-07-31 | Recruiting |
| A Randomized Phase III Study of Neo-Adjuvant Docetaxel and Androgen Deprivation Prior to Radical Prostatectomy Versus Immediate Radical Prostatectomy in Patients With High-Risk, Clinically Localized Prostate Cancer [NCT00430183] | Phase 3 | 788 participants (Actual) | Interventional | 2007-05-08 | Active, not recruiting |
| A Phase I/II Trial of Preoperative Oxaliplatin, Docetaxel, and Capecitabine With Concurrent Radiation Therapy in Localized Carcinoma of the Esophagus or Gastroesophageal Junction [NCT00193128] | Phase 1/Phase 2 | 59 participants (Actual) | Interventional | 2004-04-30 | Completed |
| Drug Treatment Patterns and Effects for Metastatic Non-small Cell Lung Cancer Patients In NORway (DELINOR) [NCT05834348] | | 20,605 participants (Anticipated) | Observational | 2023-06-26 | Recruiting |
| A Phase I/II Study of Concurrent Weekly Docetaxel (Taxotere®), Androgen Ablation, and Adaptive External Beam Radiotherapy for Localized High-Risk Adenocarcinoma of the Prostate [NCT00225420] | Phase 1/Phase 2 | 23 participants (Actual) | Interventional | 2005-08-31 | Completed |
| A Randomized Phase II Study of Preoperative Herceptin/Navelbine Versus Taxotere/Carboplatin/Herceptin in Early Stage, HER-2 Positive Breast Cancer [NCT00148668] | Phase 2 | 81 participants (Actual) | Interventional | 2003-12-31 | Completed |
| An Open-Label, Multicenter Extension Study of Trastuzumab Emtansine Administered as a Single Agent or in Combination With Other Anti-Cancer Therapies in Patients Previously Enrolled in a Genentech and/or F. Hoffmann-La Roche Ltd-Sponsored Trastuzumab Emta [NCT00781612] | Phase 2 | 720 participants (Anticipated) | Interventional | 2008-10-16 | Recruiting |
| Phase III Study of Osimertinib or Docetaxel-bevacizumab as Third-line Treatment in EGFR T790M Mutated Non-Small Cell Lung Cancer [NCT02959749] | Phase 2/Phase 3 | 147 participants (Actual) | Interventional | 2015-08-31 | Completed |
| A Phase I/II Trial of Induction Cisplatin and Docetaxel Followed by Concomitant Docetaxel/Radiotherapy With Subcutaneous Amifostine for Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT00318890] | Phase 1/Phase 2 | 48 participants (Actual) | Interventional | 2002-10-31 | Completed |
| An Open-label, Dose-finding Study to Evaluate the Safety of AMG 706 in Combination With Paclitaxel or Docetaxel as Treatment for Locally Recurrent or Metastatic Breast Cancer [NCT00322400] | Phase 1 | 46 participants (Actual) | Interventional | 2006-03-31 | Completed |
| A Multinational, Multicenter, Phase III Open Randomized Trial With or Without Consolidation Chemotherapy Using Docetaxel and Cisplatin After Concurrent Chemoradiation in Inoperable Stage III Non-small Cell Lung Cancer (CCheIN) [NCT00326378] | Phase 3 | 434 participants (Actual) | Interventional | 2005-10-31 | Completed |
| 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 2 | 93 participants (Actual) | Interventional | 2016-09-01 | Completed |
| A Retrospective, Longitudinal Multi-Center Study of Radium-223 in Patients With Metastatic Castration-Resistant Prostate Cancer [NCT03419442] | | 150 participants (Actual) | Observational | 2018-12-03 | Completed |
| A Phase Ib, Open-Label, Multicenter Study of the Safety and Pharmacokinetics of the Combination of RhuMab 2C4 (Omnitarg), a Recombinant Humanized Antibody to HER2, and Docetaxel (Taxotere) in Patients With Advanced Solid Tumors [NCT02490475] | Phase 1 | 19 participants (Actual) | Interventional | 2004-02-29 | Completed |
| Concurrent Helical Tomotherapy With Chemotherapy in Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC): a Phase I/II Trial of Radiation Dose Escalation and Fixed Dose Chemotherapy. [NCT00379717] | Phase 1/Phase 2 | 30 participants (Anticipated) | Interventional | 2006-11-30 | Recruiting |
| Neoadjuvant Epirubicin/Cyclophosphamide Followed by Docetaxel Combined With Trastuzumab for the Patients With HER-Positive Advanced Breast Cancer [NCT00379015] | Phase 2 | 38 participants (Actual) | Interventional | 2006-01-31 | Completed |
| A Phase II Safety and Tolerability Study of Avastin When Added to Single-agent Chemotherapy to Treat Patient With Breast Cancer Metastatic to Brain [NCT00476827] | Phase 2 | 16 participants (Actual) | Interventional | 2007-05-31 | Terminated(stopped due to Slow accrual) |
| A Pilot Phase I/II Study to Evaluate the Effects of Taxotere/Prednisone Plus Sunitinib in Chemotherapy-Naïve, Hormone Refractory Prostate Cancer Patients With Biochemical Relapse [NCT00879619] | Phase 1/Phase 2 | 4 participants (Actual) | Interventional | 2009-07-31 | Terminated(stopped due to Terminated due to slow accrual.) |
| A Phase 1b/2 Study of the Oral CDK4/6 Inhibitor LEE011 (Ribociclib) in Combination With Docetaxel Plus Prednisone in Metastatic Castration Resistant Prostate Cancer [NCT02494921] | Phase 1/Phase 2 | 43 participants (Actual) | Interventional | 2015-11-20 | Completed |
| A Phase II Organ Preservation Trial Using Cetuximab and Radiation Therapy in Advanced Laryngeal Cancer Patients Who Have Responded to One Cycle of Induction Chemotherapy With Taxotere, Cisplatin, 5-Fluorouracil (TPF), and Cetuximab [NCT00599131] | Phase 2 | 4 participants (Actual) | Interventional | 2007-08-31 | Terminated(stopped due to The study was discontinued prematurely due to early stopping rules.) |
| Pilot Neoadjuvant Trial of Chemohormonal Therapy Followed by Prostatectomy in Patients With High Risk or Oligometastatic Prostate Cancer [NCT03358563] | Early Phase 1 | 30 participants (Actual) | Interventional | 2018-01-17 | Completed |
| A Multi-institutional Open Label, Trial Evaluating the Efficacy of Gemcitabine and Docetaxel in Patients With Relapsed or Refractory Metastatic Colorectal Adenocarcinoma With Methylated CHFR and/or Microsatellite Instability Phenotype [NCT01639131] | Phase 2 | 6 participants (Actual) | Interventional | 2012-09-10 | Terminated |
| 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 1 | 475 participants (Anticipated) | Interventional | 2016-07-08 | Recruiting |
| Taxotere Plus Concurrent Radiotherapy After Induction Chemotherapy for Squamous Cell Carcinoma of the Head and Neck (TAXT-XRT) [NCT00003200] | Phase 1 | 22 participants (Actual) | Interventional | 1995-10-31 | Completed |
| 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 3 | 1,050 participants (Anticipated) | Interventional | 1998-10-31 | Completed |
| A Phase II Study of Docetaxel and Carboplatin for Suboptimally Debulked Stage III or Stage IV Ovarian and Fallopian Tube Carcinoma [NCT00003560] | Phase 2 | 40 participants (Anticipated) | Interventional | 1998-05-31 | Active, 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 1 | 0 participants | Interventional | 1999-07-31 | Completed |
| A RANDOMIZED TRIAL COMPARING PREOPERATIVE DOXORUBICIN (ADRIAMYCIN)/CYCLOPHOSPHAMIDE (AC) TO PREOPERATIVE AC FOLLOWED BY PREOPERATIVE DOCETAXEL (TAXOTERE) AND TO PREOPERATIVE AC FOLLOWED BY POSTOPERATIVE DOCETAXEL IN PATIENTS WITH OPERABLE CARCINOMA OF THE [NCT00002707] | Phase 3 | 2,411 participants (Actual) | Interventional | 1995-12-31 | Completed |
| "Randomized Phase II Clinical Study of Radiation Therapy, Hormone Therapy and Chemotherapy With Docetaxel Versus Radiation Therapy and Hormone Therapy in Patients With High-Risk Localized Prostate Cancer (Stage III and IV)" [NCT03432780] | Phase 2 | 134 participants (Actual) | Interventional | 2008-12-18 | Active, not recruiting |
| Phase I Study to Determine the Safety of MS-209 in Combination With Docetaxel in Patients With a Solid Progressive Tumor [NCT00004886] | Phase 1 | 30 participants (Actual) | Interventional | 1999-12-31 | Completed |
| A Phase III Trial of Preoperative vs. Postoperative Chemotherapy With Taxotere-Cisplatin-5FU (TCF) in Patients With Locally Advanced Operable Gastric Carcinoma [NCT00005060] | Phase 3 | 240 participants (Actual) | Interventional | 1999-11-30 | Completed |
| Docetaxel Followed by Radical Prostatectomy in Patients With High Risk Localized Prostate Cancer [NCT00005096] | Phase 2 | 19 participants (Actual) | Interventional | 1999-12-31 | Completed |
| A Phase II Study of Estramustine, Docetaxel, and Carboplatin With G-CSF Support in Men With Hormone Refractory Prostate Cancer [NCT00005810] | Phase 2 | 40 participants (Actual) | Interventional | 2000-03-31 | Completed |
| A Multicenter, Multinational, Phase II Study to Evaluate Perjeta in Combination With Herceptin and Standard Neoadjuvant Anthracycline-Based Chemotherapy in Patients With HER2-Positive, Locally Advanced, Inflammatory, or Early-Stage Breast Cancer [NCT02132949] | Phase 2 | 401 participants (Actual) | Interventional | 2014-07-14 | Completed |
| Phase I/II Trial of the Combination of Docetaxel, Gemcitabine and Cisplatin (DGP) as Induction Chemotherapy in Patients With Stage III Non-Small Cell Lung Cancer [NCT00003037] | Phase 1/Phase 2 | 0 participants | Interventional | 1997-04-30 | Completed |
| A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Chemotherapy in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer After Failure With Pla [NCT02302807] | Phase 3 | 931 participants (Actual) | Interventional | 2015-01-13 | Completed |
| A Randomised Comparative Trial of Adriamycin + Taxotere vs. Adriamycin + Cyclophosphamide as Primary Medical Therapy for Patients With Potentially Operable Breast Cancer Greater Than or Equal to 3 cm Diameter, Locally Advanced, or Inflammatory Disease [NCT00003679] | Phase 3 | 350 participants (Anticipated) | Interventional | 1998-11-30 | Active, not recruiting |
| Phase II Study of Weekly Docetaxel (Taxotere) in Hormone Refractory Metastatic Prostate Cancer [NCT00003781] | Phase 2 | 25 participants (Actual) | Interventional | 1998-12-31 | Completed |
| A Phase I Study of Oxaliplatin in Combination With Docetaxel (Taxotere) Metastatic/Recurrent Solid Tumors [NCT00004243] | Phase 1 | 0 participants | Interventional | 2000-03-31 | Completed |
| Taxotere-Cisplatin-5FU (TCF) Versus Taxotere-Cisplatin (TC) Versus Epirubicin-Cisplatin-5FU (ECF) as Systemic Treatment for Advanced Gastric Carcinoma: A Randomized Phase II Trial [NCT00004873] | Phase 2 | 0 participants | Interventional | 1999-08-31 | Completed |
| A Phase I - II Open Label Study of the Maximum Tolerated Dose, Safety and Efficacy of Docetaxel and Cisplatin Plus STI571 in Advanced Non-Small Cell Lung Cancer [NCT02127372] | Phase 1/Phase 2 | 43 participants (Actual) | Interventional | 2004-11-30 | Terminated(stopped due to The study was closed due to poor accrual) |
| A Pilot Trial of Platinum, Gemcitabine, or Pemetrexed Single- or Multi-Agent Therapy With Serial Tumor Specimen Collection in Patients With Advanced Non-Small-Cell Lung Cancer [NCT02145078] | | 4 participants (Actual) | Interventional | 2014-06-30 | Terminated(stopped due to Slow accrual.) |
| 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 1 | 51 participants (Actual) | Interventional | 2014-04-01 | Completed |
| A Phase III Open-Label, Multicenter Trial of Avelumab (MSB0010718C) Versus Docetaxel in Subjects With Non-Small Cell Lung Cancer That Has Progressed After a Platinum-Containing Doublet [NCT02395172] | Phase 3 | 792 participants (Actual) | Interventional | 2015-03-24 | Completed |
| Phase I/II Study of Docetaxel (Taxotere) in Combination With Doxorubicin HCI Liposome Injection (Doxil) in Advanced Androgen-Independent Prostate Cancer (AIPC) [NCT00456989] | Phase 1/Phase 2 | 39 participants (Actual) | Interventional | 2004-01-31 | Completed |
| Open-label, Multicenter Phase 1 Study of Mogamulizumab (KW-0761) in Combination With Docetaxel in Previously Treated Subjects With Non-small Cell Lung Cancer (NSCLC) [NCT02358473] | Phase 1 | 13 participants (Actual) | Interventional | 2015-01-31 | Completed |
| 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 2 | 369 participants (Anticipated) | Interventional | 2022-12-20 | Recruiting |
| Comparison of With and Without Sequential Single Drug Therapy of S-1 After Adjuvant Chemotherapy With Docetaxel Plus S-1 in Stage III Gastric Cancer [NCT05813015] | Phase 3 | 70 participants (Anticipated) | Interventional | 2023-01-28 | Recruiting |
| A Phase 3 Open-Label, Randomized, Multicenter Study of NKTR-102 Versus Treatment of Physician's Choice (TPC) in Patients With Metastatic Breast Cancer Who Have Stable Brain Metastases and Have Been Previously Treated With an Anthracycline, a Taxane, and C [NCT02915744] | Phase 3 | 178 participants (Actual) | Interventional | 2016-11-30 | Completed |
| Validation of a Radiation Response Signature in Borderline Resectable Pancreatic Cancer Patients Treated With Induction Chemotherapy Followed by Stereotactic Body Radiation Therapy (SBRT) [NCT01754623] | Phase 2 | 9 participants (Actual) | Interventional | 2013-02-28 | Terminated(stopped due to Lack of pre-treatment tissue to make the study plan feasible.) |
| Program for Assessment of Capecitabine (Xeloda) Plus Docetaxel First-line Therapies in HER2-negative Metastatic Breast Cancer (XEBRA Study) [NCT01777945] | | 46 participants (Actual) | Observational | 2012-12-31 | Completed |
| A Phase I/Randomized Phase II Study of Docetaxel With or Without AZD4547 in Recurrent FGFR1-Amplified Squamous Non-Small Cell Lung Cancer [NCT01824901] | Phase 1/Phase 2 | 2 participants (Actual) | Interventional | 2014-01-15 | Completed |
| 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 2 | 60 participants (Anticipated) | Interventional | 2023-02-01 | Not yet recruiting |
| Perioperative RAMucirumab in Combination With FLOT Versus FLOT Alone for reSEctable eSophagogastric Adenocarcinoma - RAMSES - a Phase II/III Trial of the AIO [NCT02661971] | Phase 2/Phase 3 | 180 participants (Actual) | Interventional | 2016-06-30 | Completed |
| A Study of the Safety and Efficacy of the Combination of Gemcitabine and Docetaxel With MORAb-004 in Metastatic Soft Tissue Sarcoma [NCT01574716] | Phase 2 | 209 participants (Actual) | Interventional | 2012-08-07 | Completed |
| A Phase II Study of Bevacizumab With Docetaxel and Capecitabine in the Neoadjuvant Setting for Breast Cancer Patients [NCT02005549] | Phase 2 | 18 participants (Actual) | Interventional | 2006-02-28 | Completed |
| Efficacy and Safety of Apantamide Combined With Docetaxel and ADT vs. Apantamide Combined With ADT in Patients With High Tumor Burden mHSPC: a Multicenter and Prospective Cohort Study [NCT05713578] | Early Phase 1 | 220 participants (Anticipated) | Interventional | 2023-03-01 | Recruiting |
| A Phase II, Single-arm Study of Docetaxel and Oxaliplatin in Metastatic Cisplatin-resistant Transitional Cell Carcinoma of the Urinary Bladder [NCT03159143] | Phase 2 | 22 participants (Actual) | Interventional | 2004-12-17 | Completed |
| A Randomized Controlled Study of AC (Doxorubicin Hydrochloride Liposome/Cyclophosphamide) vs TC (Docetaxel/Cyclophosphamide) Regimens for Postoperative Adjuvant Chemotherapy in Patients With HR-positive, HER2-negative Early Breast Cancer [NCT05302336] | Phase 4 | 402 participants (Anticipated) | Interventional | 2022-05-01 | Recruiting |
| A Multicenter, Randomized, Double-blind, Parallel-controlled Clinical Study to Evaluate the Efficacy and Safety of TQB2440 Injection/Perjeta ® Combined With Trastuzumab and Docetaxel in Patients With Early or Locally Advanced ER/ PR-negative HER2-positive [NCT05985187] | Phase 3 | 412 participants (Actual) | Interventional | 2020-10-20 | Active, not recruiting |
| Phase 2a Open-Label, Multicenter Trial of Naptumomab Estafenatox (NAP) in Combination With Docetaxel Following Obinutuzumab Pretreatment in Subjects With Checkpoint Inhibitor Pretreated Advanced or Metastatic Non-Small Cell Lung Cancer [NCT04880863] | Phase 2 | 38 participants (Actual) | Interventional | 2021-10-26 | Active, not recruiting |
| A Randomized, Open-label Phase II/III Efficacy and Safety Study of Atezolizumab in Combination With FLOT Versus FLOT Alone in Patients With Gastric Cancer and Adenocarcinoma of the Oesophago-gastric Junction and High Immune Responsiveness (MO30039/MO43340 [NCT03421288] | Phase 2 | 674 participants (Anticipated) | Interventional | 2018-09-14 | Recruiting |
| DART-HPV: A Phase III Evaluation of De-escalated Adjuvant Radiation Therapy for HPV-Associated Oropharynx Cancer [NCT02908477] | Phase 3 | 227 participants (Actual) | Interventional | 2016-10-03 | Active, not recruiting |
| A Phase II Study of Docetaxel and Modulation of Autophagy With Hydroxychloroquine for Metastatic Hormone Refractory Prostate Cancer [NCT00786682] | Phase 2 | 11 participants (Actual) | Interventional | 2008-12-31 | Terminated(stopped due to Lack of improved efficacy compared to historical controls, competing studies) |
| Phase II Study of Weekly Docetaxel Together With Weekly Cisplatin in Chemotherapy-Naive Patients With Stage IV or Select Stage IIIB (Malignant Effusion) Non-Small Cell Lung Cancer [NCT00118131] | Phase 2 | 49 participants (Actual) | Interventional | 2003-12-31 | Terminated(stopped due to Slow accrual) |
| 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 3 | 600 participants (Anticipated) | Interventional | 1997-08-31 | Completed |
| Preoperative Chemotherapy in Non-Small Cell Lung Cancer (NSCLC) Patients With Mediastinal Lymph Node Metastases (Stage IIIA, N2) [NCT00003231] | Phase 2 | 40 participants (Anticipated) | Interventional | 1997-04-30 | Completed |
| Phase I Study of Oxaliplatin in Combination With Docetaxel and Radiotherapy in Patients With Unresectable or Recurrent Non-Small Cell Lung Cancer (NSCLC) [NCT00356941] | Phase 1 | 4 participants (Actual) | Interventional | 2006-04-30 | Terminated(stopped due to Withdrawn due to lack of accrual) |
| A Multicenter, Randomized, Double-blind, Parallel-controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of AL2846 Capsules Combined With TQB2450 Injection Compared With Docetaxel Injection in Patients With Advanced Non-small Cell Lung Ca [NCT05922345] | Phase 3 | 518 participants (Anticipated) | Interventional | 2023-06-08 | Recruiting |
| 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 3 | 1,406 participants (Anticipated) | Interventional | 2023-06-07 | Recruiting |
| 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 2 | 85 participants (Anticipated) | Interventional | 2021-10-22 | Recruiting |
| 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 3 | 501 participants (Actual) | Interventional | 2020-04-07 | Active, not recruiting |
| A Phase II, Randomized, Open-label Platform Trial Utilizing a Master Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC Participants [NCT03739710] | Phase 2 | 185 participants (Anticipated) | Interventional | 2019-01-24 | Recruiting |
| A Multicenter, Open-Label, Randomized-Controlled Study of Abemaciclib, a CDK4 and 6 Inhibitor, in Combination With Fulvestrant Compared to Chemotherapy in Women With HR Positive, HER2 Negative Metastatic Breast Cancer With Visceral Metastases [NCT04031885] | Phase 4 | 4 participants (Actual) | Interventional | 2019-08-14 | Terminated(stopped due to Business decision based on the inability to enroll subjects into the trial) |
| Treatment of Prostate Cancer by Induction of Alternate Cell Death Pathways: A Phase I Trial of Docetaxel, Estramustine, Mitoxantrone and Prednisone [NCT00003633] | Phase 1 | 12 participants (Anticipated) | Interventional | 1998-08-31 | Active, not recruiting |
| Dose Escalation Trial of Docetaxel Plus Irinotecan in Patients With Advanced Cancer [NCT00004923] | Phase 1/Phase 2 | 47 participants (Actual) | Interventional | 1999-04-30 | Completed |
| 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 2 | 18 participants (Actual) | Interventional | 2006-01-31 | Terminated(stopped due to Sponsor withdrew financial support) |
| A Phase I Study of Docetaxel, Capecitabine and Oxaliplatin (DXO) in Patients With Advanced Stomach Cancer [NCT00446290] | Phase 1 | 22 participants (Actual) | Interventional | 2006-03-31 | Completed |
| 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 2 | 28 participants (Actual) | Interventional | 2016-02-29 | Terminated(stopped due to Terminated due to insufficient funding) |
| A Phase II Study of Definitive Therapy for Newly Diagnosed Men With Oligometastatic Prostate Cancer After Prostatectomy [NCT03043807] | Phase 2 | 26 participants (Actual) | Interventional | 2017-02-22 | Completed |
| Randomized, Multicenter, Double-blind, Phase 3 Trial of Tavocept Versus Placebo in Patients With Newly Diagnosed or Relapsed Advanced Primary Adenocarcinoma of the Lung Treated With Docetaxel or Paclitaxel Plus Cisplatin [NCT00966914] | Phase 3 | 540 participants (Actual) | Interventional | 2010-04-30 | Completed |
| A Randomized, Open-Label, Active-Controlled, Multi-Center Study to Compare Efficacy, Safety, and Tolerability of KN046 Combined With Lenvatinib Versus Docetaxel in Subjects With Non-Small Cell Lung Cancer After Failure of Anti-PD-(L)1 Agent [NCT05001724] | Phase 2/Phase 3 | 16 participants (Actual) | Interventional | 2021-10-28 | Terminated(stopped due to Because the efficacy data did not meet expectations, the sponsor decided to terminate the study.) |
| Efficacy and Safety of Perioperative Chemotherapy Combined With Tislelizumab and Trastuzumab in Patients With HER2-positive Resectable Gastric or Gastr-oesophageal Junction Carcinoma (GC/EGJ) -- a Prospective, Single-arm, Phase II Study [NCT04819971] | Phase 2 | 67 participants (Anticipated) | Interventional | 2021-12-01 | Recruiting |
| A Phase 2 Study of Docetaxel Plus Apalutamide in Castration-Resistant Prostate Cancer Patients Post Abiraterone Acetate [NCT03093272] | Phase 2 | 9 participants (Actual) | Interventional | 2017-06-23 | Terminated(stopped due to Safety concerns) |
| 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 3 | 226 participants (Actual) | Interventional | 2014-09-23 | Completed |
| Phase 2 Study of Pembrolizumab Combined With Chemoradiation Therapy in Anaplastic Thyroid Cancer [NCT03211117] | Phase 2 | 3 participants (Actual) | Interventional | 2017-08-14 | Completed |
| A Phase I Trial of Docetaxel and Low-Dose Fractionated Radiation in the Treatment of Metastatic or Recurrent Non-Small Cell Lung Cancer (NSCLC) [NCT00378404] | Phase 1 | 10 participants (Actual) | Interventional | 2004-11-30 | Terminated(stopped due to Slow accrual) |
| 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 1 | 398 participants (Actual) | Interventional | 2015-02-02 | Completed |
| Phase III Randomized Clinical Trial Evaluating the Sequencing of Anthracyclines and Taxanes in Neoadjuvant Therapy for Locally Advanced HER2-negative Breast Cancer [NCT04540692] | Phase 3 | 494 participants (Anticipated) | Interventional | 2021-01-12 | Recruiting |
| A Randomized Phase II Pilot Study Prospectively Evaluating Treatment for Patients Based on ERCC1(Excision Repair Cross-Complementing 1) for Advanced/Metastatic Esophageal, Gastric or Gastroesophageal Junction (GEJ) Cancer [NCT01498289] | Phase 2 | 213 participants (Actual) | Interventional | 2012-02-29 | Completed |
| Phase II Study of Dose Attenuated Chemotherapy in Patients With Lung Cancer and Age > 70 and/or Comorbidities [NCT05800587] | Phase 2 | 280 participants (Anticipated) | Interventional | 2023-02-22 | Recruiting |
| Effect of NST Whole-course Nutritional Management on Nutritional Status and Adverse Reactions in Patients With Esophageal Cancer Undergoing Concurrent Chemoradiotherapy [NCT05800054] | | 210 participants (Anticipated) | Interventional | 2021-01-01 | Recruiting |
| Docetaxel Alone or in Combination With Enzalutamide as First-line Treatment for Metastatic Castration Resistant Prostate Cancer Previously Treated With Abiraterone: a Single Center, Randomized, Open-label Study [NCT05627752] | Phase 2/Phase 3 | 120 participants (Anticipated) | Interventional | 2023-06-01 | Recruiting |
| A Randomized Phase II Trial of Low Stathmin Expression as a Predictive Biomarker for OSCC Patients Receiving TPF Induction Chemotherapy Followed by Radical Surgery and Radiotherapy/Chemoradiotherapy [NCT03326947] | Phase 2 | 60 participants (Anticipated) | Interventional | 2018-01-01 | Recruiting |
| A Randomized Controlled Clinical Trial to Evaluate the Efficacy and Safety of Ultrasound Hyperthermia in Combination With Chemotherapy on Oral and Maxillofacial-Head and Neck Cancer [NCT02353260] | Phase 2 | 120 participants (Anticipated) | Interventional | 2014-12-31 | Recruiting |
| A Randomized Controlled Trial to Evaluate the Efficacy and Safety of Docetaxel Combined With Platinum-based Drugs Compared With Docetaxel Alone for Metastatic Hormone-sensitive Prostate Cancer Patients Carrying DNA Repair Mutation [NCT05461261] | Phase 2 | 50 participants (Anticipated) | Interventional | 2022-07-01 | Recruiting |
| A Randomized, Open Label, Multicenter, Phase III, 2-Arm Study of Androgen Deprivation +/- Taxotere (Docetaxel) for Non-metastatic Prostate Cancer Patients With a Rising PSA [NCT03119857] | Phase 3 | 349 participants (Actual) | Interventional | 2009-02-28 | Active, not recruiting |
| A Phase IB Dose Escalation and Expansion Trial of MEK 162 With Docetaxel in Previously Treated Stage IV, Non-small Cell Lung Cancer (NSCLC) [NCT02451865] | Phase 1 | 0 participants (Actual) | Interventional | 2016-06-30 | Withdrawn |
| Safety of Xeloda in Solid Tumours [NCT02479217] | | 1,268 participants (Actual) | Observational | 2006-07-31 | Completed |
| A Pilot Study of Mobilization and Treatment of Disseminated Tumor Cells in Men With Metastatic Prostate Cancer [NCT02478125] | Phase 1 | 3 participants (Actual) | Interventional | 2016-07-31 | Terminated(stopped due to Low accrual) |
| An Open Label, Phase 1, Treatment Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of IDE397 (MAT2A Inhibitor) In Adult Participants With Advanced Solid Tumors [NCT04794699] | Phase 1 | 130 participants (Anticipated) | Interventional | 2021-04-14 | Recruiting |
| Phase 3, Two-stage, Randomized Study of ONC-392 Versus Docetaxel in Metastatic Non-Small Cell Lung Cancers That Progressed on PD-1/PD-L1 Inhibitors [NCT05671510] | Phase 3 | 600 participants (Anticipated) | Interventional | 2023-06-28 | Recruiting |
| A Randomized, Parallel Control, Exploratory Trial to Compare Apatinib Plus Chemotherapy Drug Versus Chemotherapy Drug as Second-line Treatment in Subjects With Advanced or Metastatic of the Non-small Cell Lung Cancer (NSCLC) [NCT03256721] | Phase 2 | 37 participants (Actual) | Interventional | 2017-08-16 | Terminated(stopped due to Due to the enrollment was slow and exceeded the expected enrollment time) |
| Docetaxel, Oxaliplatin, Fluorouracil (FLOT Regimen) Combined With Teriprizumab (PD-1) in the First-line Treatment of Patients With Advanced Gastric Cancer and Peritoneal Metastasis: an Open, One-arm, Exploratory Study [NCT04886193] | | 20 participants (Anticipated) | Interventional | 2021-04-16 | Recruiting |
| CHemotherapy Plus Enzalutamide In First Line Therapy for Castration Resistant prOstate caNcer [NCT02453009] | Phase 2 | 232 participants (Anticipated) | Interventional | 2014-10-31 | Recruiting |
| Two Independent Phase 1b Cohorts of Docetaxel or Cabazitaxel in Combination With the Potent CYP3A4 Inhibitor, Clarithromycin [NCT03043989] | Phase 1 | 4 participants (Actual) | Interventional | 2017-03-21 | Terminated(stopped due to Low accrual) |
| 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 2 | 100 participants (Anticipated) | Interventional | 2021-10-20 | Recruiting |
| Randomized Open-label, Multicentric, Phase II Clinical Trial to Evaluate the Efficacy of a Neoadjuvant Chemotherapy Scheme Customized by Levels of BRCA1 in Women With Primary HER2 Negative Breast Cancer (The BERNAQ Clinical Trial) [NCT02365805] | Phase 2 | 30 participants (Actual) | Interventional | 2014-04-30 | Completed |
| Combination of Docetaxel, Cisplatin, and Capecitabine (DCX) in the Treatment of Locally Advanced or Metastatic Nasopharyngeal Carcinoma: a Prospective, Phase 2 Study [NCT02360501] | Phase 2 | 50 participants (Actual) | Interventional | 2008-01-31 | Completed |
| A Phase Ib/II Study of Pembrolizumab Plus Chemotherapy in Patients With Advanced Cancer (PembroPlus) [NCT02331251] | Phase 1/Phase 2 | 81 participants (Actual) | Interventional | 2014-12-31 | Terminated(stopped due to PI not longer at site.) |
| A Study of Population Pharmacokinetics of Docetaxel (Taxotere) in Caucasian and African-American Cancer Patients [NCT00003565] | Phase 2 | 109 participants (Actual) | Interventional | 1998-09-30 | Completed |
| A Randomized, Multicenter Study To Evaluate The Efficacy And Safety Of Apatinib Versus Docetaxel In Patients With Previously Treated Locally Advanced Or Metastatic Gastric Cancer, Including Adenocarcinoma Of The Gastroesophageal Junction [NCT02409199] | Phase 2/Phase 3 | 66 participants (Anticipated) | Interventional | 2015-06-30 | Recruiting |
| 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 2 | 68 participants (Anticipated) | Interventional | 2020-06-21 | Recruiting |
| A Phase II, Prospective, Single-center, Randomized, Controlled Study to Investigate the Efficacy and Safety of Sintilimab or Placebo in Combination With Chemotherapy as Second-line Treatment for Patients With Stage IV Nonsquamous Non-small Cell Lung Cance [NCT03863483] | Phase 2 | 70 participants (Anticipated) | Interventional | 2019-03-26 | Recruiting |
| A Phase 1/1b Study to Evaluate the Safety and Tolerability of AB801 Monotherapy and Combination Therapy in Participants With Advanced Malignancies [NCT06120075] | Phase 1 | 80 participants (Anticipated) | Interventional | 2023-12-01 | Not yet recruiting |
| SAFFRON-301: A Randomized Phase 3 Study of Tislelizumab in Combination With Sitravatinib in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer That Progressed on or After Platinum-Based Chemotherapy and Anti-PD-(L)1 Antibody [NCT04921358] | Phase 3 | 351 participants (Anticipated) | Interventional | 2021-07-27 | Active, not recruiting |
| Phase II Randomized Trial of Gemcitabine/Docetaxel and Gemcitabine/Irinotecan in Stage IIIB/IV Non-Small Cell Lung Cancer [NCT00004139] | Phase 2 | 80 participants (Actual) | Interventional | 1999-09-30 | Completed |
| TRITON3: A Multicenter, Randomized, Open Label Phase 3 Study of Rucaparib Versus Physician's Choice of Therapy for Patients With Metastatic Castration Resistant Prostate Cancer Associated With Homologous Recombination Deficiency [NCT02975934] | Phase 3 | 405 participants (Actual) | Interventional | 2017-06-13 | Active, not recruiting |
| A Phase I Study of Estramustine, Taxotere and Carboplatin (ETP) in Patients With Horomone Refractory Prostate Cancer [NCT00005627] | Phase 1 | 0 participants | Interventional | 1999-03-31 | Completed |
| A Randomized Trial of Trastuzumab Deruxtecan and Biology-Driven Selection of Neoadjuvant Treatment for HER2-positive Breast Cancer: ARIADNE [NCT05900206] | Phase 2 | 370 participants (Anticipated) | Interventional | 2023-10-09 | Recruiting |
| An Open Label Phase I of Oral Nintedanib Plus Weekly Docetaxel Therapy in Patients With Locally Advanced or Metastatic Lung Adenocarcinoma After Failure of Platinum -Based First Line Chemotherapy [NCT02668393] | Phase 1 | 14 participants (Actual) | Interventional | 2016-03-07 | Completed |
| A Phase I Study of Pyrotinib In Combination With Docetaxel In Patients With HER2 Positive Advanced Gastric Cancer [NCT02378389] | Phase 1 | 28 participants (Anticipated) | Interventional | 2014-09-30 | Recruiting |
| A Multicenter, Randomized, Phase II Clinical Trial to Evaluate the Effect of Avastin in Combination With Neoadjuvant Treatment Regimens on the Molecular and Metabolic Characteristics and Changes in the Primary Tumors With Reference to the Obtained Respons [NCT00773695] | Phase 2 | 150 participants (Actual) | Interventional | 2008-11-07 | Completed |
| Phase III Randomized Trial of Standard Systemic Therapy (SST) Versus Standard Systemic Therapy Plus Definitive Treatment (Surgery or Radiation) of the Primary Tumor in Metastatic Prostate Cancer [NCT03678025] | Phase 3 | 1,273 participants (Anticipated) | Interventional | 2018-09-24 | Recruiting |
| A Pilot Multi-arm Study of sEphB4-HSA in Combination With Different Chemotherapy Regimens in Patients With Specific Advanced or Metastatic Solid Tumors [NCT02495896] | Phase 1 | 61 participants (Actual) | Interventional | 2015-09-03 | Terminated(stopped due to Lack of funding) |
| A Prospective Clinical Study Evaluating Xihuang Pill to Improve the Efficacy of Neoadjuvant Chemotherapy for Breast Cancer [NCT05914753] | | 200 participants (Anticipated) | Interventional | 2023-07-01 | Not yet recruiting |
| A Phase Ib/II Open Label, Multi-arm, Parallel Cohort Dose Finding and Expansion Study to Assess the Safety, Pharmacokinetics and Efficacy of NUC-3373, a Nucleotide Analogue, Given in Combination With Standard Approved Agents in Patients With Advanced Soli [NCT05714553] | Phase 1/Phase 2 | 91 participants (Anticipated) | Interventional | 2023-03-08 | Recruiting |
| The Effect of Traditional Chinese Treatment Combined Adjuvant Chemotherapy in IIIb and IIIc Gastric Cancer: A Randomized Controlled Trial [NCT03607656] | Phase 2/Phase 3 | 270 participants (Actual) | Interventional | 2018-06-08 | Completed |
| A Phase II Trial of AK112 (PD1/VEGF Bispecific) in Combination With Chemotherapy in Patients With NSCLC [NCT04736823] | Phase 2 | 296 participants (Anticipated) | Interventional | 2021-02-01 | Recruiting |
| A Randomized Open-Label Phase III Study of Sacituzumab Govitecan Versus Treatment of Physician's Choice in Subjects With Metastatic or Locally Advanced Unresectable Urothelial Cancer [NCT04527991] | Phase 3 | 696 participants (Anticipated) | Interventional | 2021-01-13 | Active, not recruiting |
| (CompassHER2-pCR): Preoperative THP and Postoperative HP in Patients Who Achieve a Pathologic Complete Response [NCT04266249] | Phase 2 | 2,156 participants (Anticipated) | Interventional | 2020-03-13 | Recruiting |
| A Phase II Randomized Trial, Non Comparative, Evaluating Chemotherapy Associated Cisplatin, 5-fluorouracil and Docetaxel at Adapted Doses in Patients With Locally Advanced Squamous Cell Carcinoma [NCT04356170] | Phase 2 | 99 participants (Anticipated) | Interventional | 2021-02-04 | Recruiting |
| [NCT01454934] | Phase 3 | 540 participants (Actual) | Interventional | 2011-12-09 | Completed |
| Induction Therapy With Gefitinib Followed by Taxane Platinum Chemotherapy and Intercalated Gefitinib in NSCLC Stages II-IIIB With Activating EGFR Mutation - A Single Arm Phase II Trial. [NCT02326285] | Phase 2/Phase 3 | 1 participants (Actual) | Interventional | 2015-11-30 | Terminated(stopped due to Due to low patient enrollment was stopped. Only one patient could be enrolled. 37 patients were pre-screened, but not into the inclusion criteria (wt-EGFR)) |
| 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 4 | 250 participants (Anticipated) | Interventional | 2014-01-31 | Recruiting |
| A Multicenter, Open-Label, Single-Arm Study of Pertuzumab in Combination With Trastuzumab and a Taxane in First Line Treatment of Patients With HER2-Positive Advanced (Metastatic or Locally Recurrent) Breast Cancer [NCT01572038] | Phase 3 | 1,436 participants (Actual) | Interventional | 2012-06-01 | Completed |
| A Phase II Evaluation of Docetaxel (NSC #628503) Plus Trabectedin (Yondelis®), R279741, IND # 101018) With Growth Factor Support in the Third-Line Treatment of Recurrent or Persistent Ovarian, Fallopian Tube or Primary Peritoneal Cancer [NCT00569673] | Phase 2 | 71 participants (Actual) | Interventional | 2008-03-31 | Completed |
| Phase I/II Trial of MK-0752 Followed by Docetaxel in Locally Advanced or Metastatic Breast Cancer: A Study by the Stem Cell Clinical Consortium [NCT00645333] | Phase 1/Phase 2 | 30 participants (Actual) | Interventional | 2008-03-31 | Completed |
| A Multicentre Phase IIb Trial to Evaluate the Efficacy and Tolerability of ModraDoc006/r in Subjects With Metastatic Castration Resistant Prostate Cancer (mCRPC), Suitable for Treatment With a Taxane [NCT04028388] | Phase 2 | 102 participants (Actual) | Interventional | 2019-07-17 | Completed |
| Food-effect Study of Weekly Administration of (bi-)Daily Oral Docetaxel (ModraDoc006) in Combination With Ritonavir [NCT03147378] | Phase 1 | 18 participants (Actual) | Interventional | 2017-05-10 | Completed |
| A Single-arm Phase II Trial of Biweekly Docetaxel and S-1 Combination Therapy as Second-line Treatment for Advanced Gastric Cancer [NCT03137004] | Phase 2 | 47 participants (Anticipated) | Interventional | 2017-06-01 | Not yet recruiting |
| A Prospective Randomized Controlled Clinical Study of Albumin-bound Paclitaxel Combined With Cisplatin (AP Regimen) Versus Docetaxel Combined With Cisplatin (TP Regimen) Induced Chemotherapy in Advanced Head and Neck Squamous Tummor [NCT04766827] | Phase 4 | 116 participants (Anticipated) | Interventional | 2020-12-12 | Recruiting |
| A Phase 3, Multicenter, Randomized, Open-label Study of SHR-A1811 (HER2-ADC) Compared With the Chemotherapy Treatment Chosen by the Investigators for Subjects With HER2-positive Metastatic and/or Unresectable Gastric Cancer or Gastroesophageal Junction Ad [NCT06123494] | Phase 3 | 360 participants (Anticipated) | Interventional | 2024-01-01 | Not yet recruiting |
| Phase II Clinical Trial of Docetaxel in Combination With Gemcitabine in Platinum-Resistant Ovarian Cancer and Primary Peritoneal Carcinoma [NCT00183794] | Phase 2 | 20 participants (Actual) | Interventional | 2002-11-30 | Completed |
| Phase 2 Study Evaluating the Safety and Efficacy of Eloxatin (Oxaliplatin) and Docetaxel as First-line Therapy of Stage IV or IIIB Unresectable Non-Small Cell Lung Cancer [NCT00145418] | Phase 2 | 15 participants (Actual) | Interventional | 2005-02-28 | Terminated(stopped due to low enrollment) |
| The Phase II Trial of SHR-1210 Combined With Preoperative Chemotherapy or Apatinib for Locally Advanced Esophageal Squamous Cell Carcinoma [NCT03917966] | Phase 2 | 80 participants (Anticipated) | Interventional | 2020-04-07 | Recruiting |
| Randomized Phase II Trial of Sequential Versus Concurrent Docetaxel and PS-341 (NSC 681239) in Previously Treated Non-Small Cell Lung Cancer (NSCLC) [NCT00362882] | Phase 2 | 81 participants (Actual) | Interventional | 2006-07-31 | Completed |
| Phase II Study of Sequential Dose-Dense Chemotherapy and Dose-Intense Erlotinib for the Initial Treatment of Advanced Non-Small Cell Lung Cancer [NCT01557959] | Phase 2 | 45 participants (Actual) | Interventional | 2007-07-31 | Completed |
| Multicenter Study Investigating Utilization of Pharmacokinetic(PK)-Guided Docetaxel in Senior Adult Breast Cancer Patients Receiving Docetaxel and Cyclophosphamide (TC) Chemotherapy [NCT02502864] | Phase 4 | 9 participants (Actual) | Interventional | 2016-02-09 | Completed |
| A Prospective, Randomized Clinical Study of Safety and Efficacy by Using Docetaxel With or Without Traditional Chinese Medicine XH1 in Patients With Stage ⅢB-Ⅳ Non-small Cell Lung Cancer (NSCLC) Who Failed With First-line Chemotherapy [NCT03407300] | Phase 2 | 80 participants (Anticipated) | Interventional | 2018-02-01 | Recruiting |
| A Phase 2 Trial of Bevacizumab, Lenalidomide, Docetaxel, and Prednisone (ART-P) for Treatment of Metastatic Castrate-Resistant Prostate Cancer [NCT00942578] | Phase 2 | 63 participants (Actual) | Interventional | 2009-07-16 | Completed |
| A Phase 2 Randomized, Double-blind, Clinical Trial of Trilaciclib Versus Placebo in Patients With Metastatic Non-Small Cell Lung Cancer (NSCLC) Treated With Docetaxel in the 2nd/3rd Line Setting (PRESERVE 4) [NCT04863248] | Phase 2 | 10 participants (Actual) | Interventional | 2021-04-30 | Terminated(stopped due to Treatment paradigm in second- and third-line NSCLC is shifting away from docetaxel, the backbone chemotherapy therapy used in this study.) |
| Immunotherapy With Chemotherapy and Chemoradiation for Advanced Squamous Cancer of Nasal Cavity / Paranasal Sinuses (I-NAPA) [NCT05027633] | Phase 2 | 35 participants (Anticipated) | Interventional | 2021-11-02 | Recruiting |
| A Randomized Phase 2 Trial of Ascorbic Acid in Combination With Docetaxel in Men With Metastatic Prostate Cancer [NCT02516670] | Phase 2 | 50 participants (Actual) | Interventional | 2016-06-20 | Terminated(stopped due to insufficient clinical response per DSMB) |
| Phase 1b Study Of Docetaxel + Pf 03084014 In Metastatic Or Locally Recurrent/Advanced Triple Negative Breast Cancer [NCT01876251] | Phase 1 | 30 participants (Actual) | Interventional | 2013-11-04 | Terminated(stopped due to The study was terminated on June 24th, 2015 due to change in strategy of PF-03084014 development. There were no safety/efficacy concerns behind the decision.) |
| A Randomized Phase II Trial of Docetaxel With or Without Bevacizumab as First-Line Therapy for Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Metastatic Breast Cancer [NCT00217672] | Phase 2 | 76 participants (Actual) | Interventional | 2005-05-31 | Completed |
| A Phase Ⅱ Study to Evaluate the Efficacy and Safety of Camrelizumab Plus Chemotherapy as Neoadjuvant Therapy With Triple Negative Breast Cancer (TNBC) [NCT05088057] | Phase 2 | 30 participants (Anticipated) | Interventional | 2021-09-20 | Recruiting |
| A Randomized, Double-Blind, Phase 2 Study of Docetaxel and Ramucirumab Versus Docetaxel and Placebo in the Treatment of Stage IV Non-Small Cell Lung Cancer Following Disease Progression After One Prior Platinum-Based Therapy [NCT01703091] | Phase 2 | 197 participants (Actual) | Interventional | 2012-12-31 | Completed |
| Multiple-center, Single-arm, Phase II Study on Sintilimab Combined With Docetaxel in Non-driver Gene Mutation Advanced NSCLC Patients Who Had Failed With Double Platinum-based Chemotherapy [NCT04144582] | Phase 2 | 30 participants (Actual) | Interventional | 2019-01-01 | Completed |
| A Phase 1 / 2 Study of CAN04, a Fully Humanized Monoclonal Antibody Against IL1RAP, in Combination With Different Chemotherapy Regimens in Subjects With Advanced Solid Tumours [NCT05116891] | Phase 1/Phase 2 | 40 participants (Actual) | Interventional | 2021-09-22 | Completed |
| A Phase II, Open-label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of MPDL3280A (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Platinum Failure [NCT01903993] | Phase 2 | 287 participants (Actual) | Interventional | 2013-08-06 | Completed |
| Apatinib Plus Camrelizumab Combined With Docetaxel and S1 in First-line Treatment for Metastatic Gastric Cancer: HCCSC G05 Trial [NCT04781686] | Phase 2 | 35 participants (Anticipated) | Interventional | 2021-05-14 | Recruiting |
| Phase III Study Comparing Concurrent Chemoradiotherapy With Weekly Docitaxel Plus Cisplatin Versus the Standard Concurrent Radiotherapy With Cisplatin in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck [NCT04780750] | Phase 3 | 60 participants (Anticipated) | Interventional | 2021-04-01 | Not yet recruiting |
| A Phase Ib/II Trial of Cadonilimab (PD-1/CTLA-4 Bispecific Antibody) in Combination With Anlotinib and Docetaxel in Patients (Pts) With Checkpoint Inhibitor (CPI)-Experienced Advanced Non-small Cell Lung Cancer (NSCLC) [NCT05816499] | Phase 1/Phase 2 | 44 participants (Anticipated) | Interventional | 2023-02-16 | Recruiting |
| 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 2 | 225 participants (Anticipated) | Interventional | 2022-10-04 | Recruiting |
| Phase II Neoadjuvant Pyrotinib Combined With Neoadjuvant Chemotherapy in HER2-low-expressing and HR Positive Early or Locally Advanced Breast Cancer: a Single-arm, Non-randomized, Single-center, Open Label Trial [NCT05165225] | Phase 2 | 48 participants (Anticipated) | Interventional | 2021-07-13 | Active, not recruiting |
| A Phase II Trial of Perioperative Chemotherapy With Leucovorin, Oxaliplatin, Docetaxel and S-1 (LOTS) For Patients With Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma [NCT04999332] | Phase 2 | 58 participants (Anticipated) | Interventional | 2021-12-10 | Recruiting |
| Multimodality Treatment for Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) (BEACON Study: Bevacizumab and Chemotherapy for Operable NSCLC) [NCT00130780] | Phase 2 | 71 participants (Actual) | Interventional | 2005-08-31 | Completed |
| Phase I/II Trial of RAD001 Plus Docetaxel in Patients With Metastatic or Recurrent Non-Small Cell Lung Cancer [NCT00406276] | Phase 1/Phase 2 | 28 participants (Actual) | Interventional | 2006-11-30 | Terminated(stopped due to data analysis showed insufficient drug efficacy) |
| 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 1 | 12 participants (Actual) | Interventional | 2006-06-30 | Terminated(stopped due to Poor accrual) |
| A PHASE 1B OPEN-LABEL THREE-ARM MULTI-CENTER STUDY TO ASSESS THE SAFETY AND TOLERABILITY OF PF-05212384 (PI3K/MTOR INHIBITOR) IN COMBINATION WITH OTHER ANTI-TUMOR AGENTS [NCT01920061] | Phase 1 | 110 participants (Actual) | Interventional | 2013-09-10 | Completed |
| Role of Neo-adjuvant Chemotherapy in Organ Preservation in Locally Advanced Squamous Cell Carcinoma of Oral Tongue [NCT02985255] | Phase 2 | 30 participants (Anticipated) | Interventional | 2016-04-30 | Recruiting |
| Phase II Trial of Bevacizumab, Docetaxel, and Oxaliplatin in Gastric and Gastroesophageal Junction Cancer [NCT00217581] | Phase 2 | 39 participants (Actual) | Interventional | 2004-10-31 | Completed |
| A Prospective, Multicenter, Randomized, Double Blind, Placebo-controlled, 2-parallel Groups, Phase 3 Study to Compare the Efficacy and Safety of Masitinib in Combination With Docetaxel to Placebo in Combination With Docetaxel in First Line Metastatic Cast [NCT03761225] | Phase 3 | 714 participants (Actual) | Interventional | 2014-09-30 | Completed |
| LUNAR: Pivotal, Randomized, Open-label Study of Tumor Treating Fields (TTFields) Concurrent With Standard of Care Therapies for Treatment of Stage 4 Non-small Cell Lung Cancer (NSCLC) Following Platinum Failure [NCT02973789] | Phase 3 | 276 participants (Actual) | Interventional | 2016-12-31 | Active, not recruiting |
| Predictors of Response to Neoadjuvant Docetaxel-Carboplatin Chemotherapy for Patients With Stage II and III Triple Negative Breast Cancer [NCT01560663] | | 415 participants (Anticipated) | Observational | 2012-01-31 | Active, not recruiting |
| A Phase I Open Label, Multicenter, Dose-Escalation Study to Determine the Maximum Tolerated Dose, Dose Limiting Toxicity, Safety and Pharmacokinetics of CGC-11047 When Used in Individual Combinations With 1) Gemcitabine or 2) Docetaxel or 3) Bevacizumab o [NCT00705874] | Phase 1 | 172 participants (Actual) | Interventional | 2006-05-31 | Completed |
| The Clinical Research of Mesylate Apatinib Combined With Docetaxel and S-1 as the First-line Treatment of Metastatic Gastric Cancer [NCT03154983] | Phase 2 | 48 participants (Anticipated) | Interventional | 2017-05-20 | Recruiting |
| Phase II Trial to Evaluate Benefit of Early Switch From First-Line Docetaxel/Prednisone to Cabazitaxel/Prednisone and the Opposite Sequence, Exploring Molecular Markers and Mechanisms of Taxane Resistance in Men With Metastatic Castration-Resistant Prosta [NCT01718353] | Phase 2 | 63 participants (Actual) | Interventional | 2013-03-31 | Completed |
| A Randomized Phase II Trial of Cytotoxic Chemotherapy With or Without Epigenetic Priming in Patients With Advanced Non-Small Cell Lung Cancer [NCT01935947] | Phase 2 | 17 participants (Actual) | Interventional | 2013-05-31 | Terminated |
| A Randomized-Controlled Three-arm Phase II Study of Lurbinectedin (PM01183) Alone or In Combination With Gemcitabine and a Control Arm With Docetaxel as Second-Line Treatment in Unresectable Non-Small Cell Lung Cancer (NSCLC) Patients [NCT01951157] | Phase 2 | 69 participants (Actual) | Interventional | 2013-09-11 | Completed |
| A Multi-Centre Randomized Study Comparing Two Standard of Care Adjuvant Chemotherapy Regimens for Lower Risk HER-2 Positive Breast Cancer [NCT03705429] | Phase 3 | 51 participants (Actual) | Interventional | 2019-05-01 | Completed |
| A Dose Increase Finding Study of Doxorubicin Hydrochloride Liposome Injection in Neoadjuvant Chemotherapy for Patients With Locally Advanced Breast Cancer [NCT03017404] | | 18 participants (Actual) | Interventional | 2015-05-31 | Completed |
| A Phase II Study to Evaluate the Effects of Docetaxel Plus Lycopene in Castration Resistant, Chemotherapy-Naïve Prostate Cancer Patients [NCT01882985] | Phase 2 | 14 participants (Actual) | Interventional | 2010-12-31 | Completed |
| 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 3 | 280 participants (Anticipated) | Interventional | 2022-02-03 | Active, not recruiting |
| A Phase 1 Study of NBTXR3 Activated by Radiotherapy With Concurrent Chemotherapy for Adenocarcinoma of the Esophagus [NCT04615013] | Phase 1 | 24 participants (Anticipated) | Interventional | 2020-11-23 | Recruiting |
| A Feasibility Trial of Nivolumab With Neoadjuvant CF or DCF Therapy for Locally Advanced Esophageal Carcinoma FRONTiER Trial [NCT03914443] | Phase 1 | 36 participants (Anticipated) | Interventional | 2019-05-07 | Active, not recruiting |
| Randomized Phase II Trial of Chemotherapy of Physician's Choice Plus Trastuzumab Versus Chemotherapy of Physician's Choice Plus Trastuzumab Plus Pertuzumab In Women With Pretreated, HER2-Overexpressing Metastatic Breast Cancer (MBC) [NCT02229149] | Phase 2 | 33 participants (Actual) | Interventional | 2014-12-31 | Terminated(stopped due to per Sponsor request) |
| 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 2 | 0 participants (Actual) | Interventional | 2021-12-06 | Withdrawn(stopped due to Upon reviewing current available combo studies, the sponsor decided to prioritize different combo study.) |
| A Phase II Study of Weekly Docetaxel (Taxotere®) in Combination With Capecitabine (Xeloda) in Advanced Gastric and Gastro-Esophageal Adenocarcinomas. [NCT00177255] | Phase 2 | 40 participants (Actual) | Interventional | 2005-04-30 | Terminated(stopped due to Roche has withdrawn support) |
| Weekly Docetaxel Plus Cisplatin as First-line Chemotherapy in Metastatic Salivary Gland Cancer Patients : a Multicenter Phase II Study [NCT05008237] | Phase 2 | 42 participants (Actual) | Interventional | 2014-05-02 | Active, not recruiting |
| 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 2 | 610 participants (Anticipated) | Interventional | 2023-05-03 | Active, not recruiting |
| A Phase II Randomized Study of Ramucirumab Plus MK3475 (Pembrolizumab) Versus Standard of Care for Patients Previously Treated With Immunotherapy for Stage IV or Recurrent Non-Small Cell Lung Cancer (Lung-MAP Non-Matched Sub-Study) [NCT03971474] | Phase 2 | 166 participants (Actual) | Interventional | 2019-05-28 | Active, not recruiting |
| Maintenance Systemic Therapy Versus Local Consolidative Therapy (LCT) Plus Maintenance Systemic Therapy for Limited Metastatic Non-Small Cell Lung Cancer (NSCLC): A Randomized Phase II/III Trial [NCT03137771] | Phase 2 | 218 participants (Actual) | Interventional | 2017-04-07 | Active, not recruiting |
| A PHASE II STUDY OF DOCETAXEL (TAXOTERE) (NSC# 628503) IN CHILDREN WITH RECURRENT SOLID TUMORS [NCT00002825] | Phase 2 | 20 participants (Actual) | Interventional | 1997-01-31 | Completed |
| A Phase II Study of Preoperative Dose-Dense Chemotherapy With Sequential Doxorubicin and Docetaxel for Initial Treatment of Operable and Inoperable Stage II-IIIB Breast Cancer [NCT00003953] | Phase 2 | 39 participants (Actual) | Interventional | 1999-02-28 | Completed |
| 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 2 | 204 participants (Actual) | Interventional | 1998-10-31 | Completed |
| Docetaxel and Estramustine Versus Mitoxantrone and Prednisone for Advanced, Hormone Refractory Prostate Cancer [NCT00004001] | Phase 3 | 770 participants (Actual) | Interventional | 1999-10-31 | Completed |
| A Phase II Study of Taxotere and Irinotecan (CPT-11) in Patients With Advanced Adenocarcinoma of the Lower Esophagus, Esophagogastric Junction, and Gastric Cardia [NCT00004235] | Phase 2 | 47 participants (Actual) | Interventional | 2000-01-31 | Completed |
| A Phase I Study of Docetaxel Plus 5-FU, Cisplatin and Leucovorin in Patients With Advanced Solid Tumors [NCT00004913] | Phase 1 | 0 participants | Interventional | 2000-01-31 | Completed |
| 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 2 | 18 participants (Anticipated) | Interventional | 2022-04-07 | Recruiting |
| 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 1 | 64 participants (Actual) | Interventional | 2013-06-10 | Completed |
| 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 1 | 65 participants (Actual) | Interventional | 2013-10-09 | Completed |
| A Phase I Study of Neoadjuvant Chemotherapy Involving Cabazitaxel, Docetaxel, Mitoxantrone or Satraplatin (CDMS) Followed by Surgery for Patients With High Risk Localized Prostate Cancer [NCT03258320] | Phase 1 | 50 participants (Anticipated) | Interventional | 2015-01-31 | Recruiting |
| Bevacizumab Combined With High-Dose Gemcitabine, Docetaxel, Melphalan, and Carboplatin in Patients With Advanced Epithelial Ovarian Cancer [NCT00583622] | Phase 2 | 13 participants (Actual) | Interventional | 2007-12-31 | Terminated(stopped due to Slow Accrual) |
| A Phase 1 Multicenter, Dose-escalation Study of LY573636-sodium in Combination With 1) Gemcitabine HCl or 2) Docetaxel or 3) Temozolomide or 4) Cisplatin, or 5) Erlotinib in Patients With Advanced Solid Tumors [NCT01284335] | Phase 1 | 234 participants (Actual) | Interventional | 2008-07-31 | Terminated(stopped due to Study was terminated due to the termination of tasisulam development.) |
| Docetaxel Followed by Radical Prostatectomy in Patients With High Risk Localized Prostate Cancer [NCT01250717] | Phase 2 | 28 participants (Actual) | Interventional | 2001-01-31 | Completed |
| Camrelizumab Plus Docetaxel and Cisplatin as First-line Therapy in Recurrent or Metastatic Oral Squamous Cell Carcinoma Patients(CHANCE): an Open-label, Single-arm, Phase II Trial [NCT05611463] | Phase 2 | 25 participants (Anticipated) | Interventional | 2020-06-02 | Recruiting |
| A Phase 1, Three-Part, Open-Label, Parallel-Cohort Safety and Tolerability Study of Relugolix in Combination With Abiraterone Acetate Plus a Corticosteroid, Apalutamide, or Docetaxel With or Without Prednisone in Men With Metastatic Castration-Sensitive P [NCT04666129] | Phase 1 | 72 participants (Anticipated) | Interventional | 2021-02-18 | Recruiting |
| A Randomized, Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced Non-Small-Cell Lung Adenocarcinoma [NCT01798485] | Phase 3 | 696 participants (Actual) | Interventional | 2013-04-30 | Terminated(stopped due to The study was stopped after the first Interim Analysis due to futility.) |
| National Phase IIIb Prospective Two-Cohort Non-Randomized, Multi-centre, Open Label Study to Assess the Safety of Subcutaneous Trastuzumab and Molecular Biomarkers in Patients With Early and Locally Advanced HER2-Positive Breast Cancer [NCT01940497] | Phase 3 | 240 participants (Actual) | Interventional | 2013-11-15 | Completed |
| The Borealis-2 Clinical Trial: A Randomized Phase 2 Study Comparing Docetaxel Alone to Docetaxel in Combination With OGX-427 in Patients With Relapsed or Refractory Metastatic Urothelial Carcinoma After Receiving a Platinum-containing Regimen: Hoosier Can [NCT01780545] | Phase 2 | 200 participants (Actual) | Interventional | 2013-04-30 | Completed |
| A Randomized, Open-label, Phase II, Multi-center Trial of Gemcitabine (G) With Pazopanib (P) or Gemcitabine (G) With Docetaxel (T) in Previously Treated Subjects With Advanced Soft Tissue Sarcoma [NCT01593748] | Phase 2 | 90 participants (Actual) | Interventional | 2012-09-27 | Completed |
| Cisplatin-Docetaxel Induction Plus Concurrent 3-D Conformal Radiotherapy and Weekly Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer Patients: A Phase II Trial [NCT03371550] | Phase 2 | 44 participants (Actual) | Interventional | 2004-08-05 | Completed |
| Mutation Scores and Differential Protein Evaluating Efficacy in Neo-adjuvant Chemotherapy and the Non-PCR Patients Treated With Sequential Nalvelbine and Xeloda in HER2(-) Luminal B Breast Cancer [NCT03359694] | Phase 3 | 300 participants (Anticipated) | Interventional | 2017-12-31 | Not yet recruiting |
| MEK114375: A Rollover Study to Provide Continued Treatment With GSK1120212 to Subjects With Solid Tumors or Leukemia [NCT01376310] | Phase 2 | 159 participants (Actual) | Interventional | 2010-11-02 | Terminated(stopped due to Company Decision) |
| Phase 2/3 Study of Dose-escalated External Beam Radiation Therapy With or Without Chemotherapy for High Risk Adenocarcinoma of the Prostate [NCT01603420] | Phase 2/Phase 3 | 2 participants (Actual) | Interventional | 2012-07-31 | Terminated(stopped due to enrollment goals not met) |
| Neoadjuvant S1, Oxaliplatin, and Docetaxel (SLOT) Versus S1, Oxaliplatin(SOX) in Patients With Locally Advanced, Resectable Gastric/Esophagogastric Junction (EGJ) Cancer [NCT02512380] | Phase 3 | 380 participants (Anticipated) | Interventional | 2015-07-31 | Recruiting |
| A Phase I Clinical Trial of AZD1775 in Combination With Neoadjuvant Weekly Docetaxel and Cisplatin Prior to Surgery in Squamous Cell Carcinoma of the Head and Neck (HNSCC) [NCT02508246] | Phase 1 | 12 participants (Actual) | Interventional | 2015-07-22 | Completed |
| Neoadjuvant Therapy and Biomarker Analysis of Stage II and III Breast Cancer With Docetaxel/Capecitabine and Celecoxib Followed by Doxorubicin/Cyclophosphamide and Celecoxib [NCT00665457] | Phase 2 | 3 participants (Actual) | Interventional | 2004-04-15 | Terminated(stopped due to study drug was removed from the market and low enrollment.) |
| Adjuvant Six Cycles of Docetaxel and Cyclophosphamide or Three Cycles of Cyclophosphamide/Epirubicin/Fluorouracil Followed by Three Cycles of Docetaxel Versus Four Cycles of Epirubicin and Cyclophosphamide Followed by Weekly Paclitaxel in Operable Breast [NCT04127019] | Phase 3 | 2,079 participants (Actual) | Interventional | 2010-06-01 | Completed |
| A Randomized, Open-Label, Active-Controlled, Multi-Center, Phase III Clinical Study of Anti-PD-1 Antibody SHR-1210 vs. Investigator's Choice of Chemotherapy in Subjects With Locally Advanced or Metastatic Esophageal Cancer [NCT03099382] | Phase 3 | 457 participants (Actual) | Interventional | 2017-05-05 | Completed |
| "International Multi-center Open-label Randomized Clinical Trial of Efficacy, Safety and Pharmacokinetics of BCD-100 (JSC BIOCAD, Russia) Monotherapy Compared to Docetaxel as Second-line Therapy of Patients With Advanced Inoperable or Metastatic Non-small [NCT03288870] | Phase 2/Phase 3 | 218 participants (Anticipated) | Interventional | 2017-09-19 | Active, 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 2 | 16 participants (Actual) | Interventional | 2013-09-24 | Completed |
| A Phase 1/2 Study Evaluating the Safety and Efficacy of ABT-751 in Combination With Docetaxel Versus Docetaxel Alone in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer [NCT00354562] | Phase 1/Phase 2 | 75 participants (Actual) | Interventional | 2007-02-28 | Terminated |
| Expanded Access to NanoDoce [NCT04060628] | | 0 participants | Expanded Access | | Available |
| A Phase 1a/b Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of GS-9716 as Monotherapy and in Combination With Anticancer Therapies in Subjects With Solid Malignancies [NCT05006794] | Phase 1 | 195 participants (Anticipated) | Interventional | 2021-09-15 | Recruiting |
| 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 2 | 1,143 participants (Anticipated) | Interventional | 2019-12-17 | Recruiting |
| A Parallel Arm Phase 1b/2a Study of DKN-01 as Monotherapy or in Combination With Docetaxel for the Treatment of Advanced Prostate Cancer With Elevated DKK1 [NCT03837353] | Phase 1/Phase 2 | 18 participants (Actual) | Interventional | 2019-04-01 | Terminated(stopped due to Terminated early due to slow accrual in the context of changing practice patterns.) |
| A Phase II Trial of Docetaxel-polymeric Micelles(PM) Plus Oxaliplatin as a First-line Chemotherapy in Patients With Esophageal Squamous Cell Carcinoma [NCT03585673] | Phase 2 | 38 participants (Anticipated) | Interventional | 2018-06-01 | Recruiting |
| Single Center, Single Arm Phase II Study on Efficacy Evaluation and Bio-marker Analysis of Sintilimab Combined With Docetaxel for Double Platinum-based Chemotherapy Failure Advanced Non-small Cell Lung Cancer [NCT03798743] | Phase 2 | 30 participants (Actual) | Interventional | 2019-01-01 | Completed |
| An Open, Multi-cohort, Phase II Clinical Study Evaluating the Efficacy and Safety of Docetaxel Polymer Micelles for Injection in Patients With Advanced Malignant Solid Tumors [NCT05254665] | Phase 2 | 110 participants (Anticipated) | Interventional | 2022-02-28 | Not yet recruiting |
| TCH (Docetaxel/Carboplatin/Trastuzumab) Versus EC -TH(Epirubicin/Cyclophosphamide Followed by Docetaxe/Trastuzumab) as Neoadjuvant Treatment for HER2-Positive Breast Cancer [NCT03140553] | Phase 2 | 140 participants (Actual) | Interventional | 2016-09-01 | Completed |
| A Phase Ib/II Study of AK104#PD-1 / CTLA-4 Bispecific Antibody# and AK117#Anti-CD47 Antibody# in Combination With or Without Chemotherapy in Advanced Malignant Tumors [NCT05235542] | Phase 1/Phase 2 | 130 participants (Anticipated) | Interventional | 2022-07-12 | Recruiting |
| Randomized Trial of Neo-adjuvant Chemotherapy With or Without Metformin for HER2 Positive Operable Breast Cancer [NCT03238495] | Phase 2 | 100 participants (Anticipated) | Interventional | 2017-08-15 | Recruiting |
| Utidelone Versus Docetaxel in HER2-negative Locally Advanced or Metastatic Breast Cancer : A Phase III, Open Label, Randomized Controlled Trial [NCT05430399] | Phase 3 | 349 participants (Anticipated) | Interventional | 2022-06-21 | Recruiting |
| Randomized Phase II Study of Standard Chemotherapy With Docetaxel With or Without Bintrafusp Alfa in Patients With Advanced NSCLC After Progressing on a Combination of Anti-PD-1/PD-L1 Agents and Chemotherapy [NCT04396535] | Phase 2 | 80 participants (Anticipated) | Interventional | 2020-10-23 | Active, not recruiting |
| A Two-arm, Open-label, Randomized Phase III Study of Pembrolizumab (MK-3475) Monotherapy Versus Standard Chemotherapy in Platinum Pre-treated, Recurrent or Metastatic Nasopharyngeal Cancer (NPC) (Keynote-122) [NCT02611960] | Phase 3 | 233 participants (Actual) | Interventional | 2016-04-18 | Completed |
| A Phase III Randomized Clinical Trial of Pembrolizumab (MK-3475) Versus Paclitaxel, Docetaxel or Vinflunine in Subjects With Recurrent or Progressive Metastatic Urothelial Cancer [NCT02256436] | Phase 3 | 542 participants (Actual) | Interventional | 2014-10-22 | Completed |
| Phase II Study of Taxotere, Doxorubicin and Cyclophosphamide (TAC) Primary Therapy in Stage III Breast Cancer [NCT00004175] | Phase 2 | 0 participants | Interventional | 1998-11-30 | Completed |
| Antitumor Immune Responses in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: a Phase II Study With Trastuzumab and Concomitant Weekly Paclitaxel in Patients With HER2+ Tumors or Epirubicin + Taxotere in HER2- Tumors. [NCT02307227] | Phase 2 | 46 participants (Actual) | Interventional | 2006-04-30 | Completed |
| Multicentre, Randomised, Double-blind, Phase III Trial to Investigate the Efficacy and Safety of Oral Nintedanib Plus Docetaxel Therapy Compared to Placebo Plus Docetaxel Therapy in Patients With Stage IIIB/IV or Recurrent, Adenocarcinoma Subtype Non-smal [NCT02231164] | Phase 3 | 12 participants (Actual) | Interventional | 2014-10-31 | Terminated |
| A Phase 1b Dose Escalation, Open-label Study Of CP-751,871 In Combination With Docetaxel In Advanced Non-hematologic Malignancies [NCT01653158] | Phase 1 | 46 participants (Actual) | Interventional | 2005-03-31 | Completed |
| A Phase I , Single Arm, Dose Escalation Study to Evaluate Tolerability, Safety, Pharmacokinetics and Preliminary Efficacy of HL-085 Plus Docetaxel in Patients With KRAS Mutant NSCLC [NCT03990077] | Phase 1 | 2 participants (Actual) | Interventional | 2020-05-21 | Terminated(stopped due to drug development strategy adjustment) |
| Phase II Clinical Study of Camrelizumab Combined With Chemotherapy or Anlotinib in Second-line or Above Therapy for Advanced Esophageal Squamous Cell Cancer Previously Treated With First-line Immunotherapy [NCT05322499] | Phase 2 | 80 participants (Anticipated) | Interventional | 2022-04-15 | Not yet recruiting |
| Clinical Study of Apatinib in Combination With Docetaxel for Patients With Advanced NSCLC After Failure of Platinum-based Double-drug Therapy [NCT03411967] | Phase 2 | 20 participants (Anticipated) | Interventional | 2018-02-01 | Not yet recruiting |
| A Study of Apatinib Plus Docetaxel for Treatment of Advanced Non-squamous Non-small Cell Lung Cancer With Bone Metastases [NCT03127319] | Phase 2 | 40 participants (Anticipated) | Interventional | 2017-07-03 | Recruiting |
| Phase II Clinical Trial of Docetaxel Plus Cisplatin as Adjuvant Chemotherapy and Concurrent Chemoradiotherapy Versus FOLFOX6 as Adjuvant and 5-FU/CF as Chemoradiotherapy in Patients of Locally Advanced Gastric Cancer After Radical Surgery [NCT01889303] | Phase 2 | 100 participants (Anticipated) | Interventional | 2013-05-31 | Recruiting |
| A Phase I/II Open-Label Dose Escalation Trial of CPI-613 in Combination With Docetaxel Chemotherapy as a Second-Line Treatment of Non-Small-Cell Lung Cancer [NCT03370159] | Phase 1/Phase 2 | 0 participants (Actual) | Interventional | 2018-06-30 | Withdrawn(stopped due to Sponsor decided not to move forward) |
| Pathological Complete Response Rate in Locally Advanced Breast Cancer With Neoadjuvant Fluorourcil/Epirubicin/Cyclophosphamide, Epirubicin/Cyclophosphamide Followed by Docetaxel, or Docetaxel/Cyclophosphamide as Neoadjuvant Chemotherapy [NCT03349177] | Phase 2/Phase 3 | 200 participants (Anticipated) | Interventional | 2017-11-27 | Not yet recruiting |
| Neoadjuvant Treatment of Breast Cancer - a Prospective Observational Study, PANnon ONCology (PANONC) Group Non-commercial Clinical Trial [NCT05131893] | | 300 participants (Anticipated) | Observational [Patient Registry] | 2022-03-31 | Not yet recruiting |
| A Randomized Phase III Comparing Sequential Therapy With Induction Chemotherapy/Chemoradiation To Cisplatinum-Based Chemoradiotherapy in Locally Advanced Hypopharyngeal Carcinoma [NCT04502641] | Phase 3 | 160 participants (Anticipated) | Interventional | 2020-08-01 | Recruiting |
| An Open-label, Randomized, Positive Drug-controlled Phase Ⅱ Study to Compare the Efficacy and Safety of HB1801 to Taxotere in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer [NCT05863325] | Phase 2 | 80 participants (Anticipated) | Interventional | 2023-06-27 | Recruiting |
| A Phase III, Open-label, Randomized, Controlled Clinical Study of Utidelone Versus Docetaxel in Patients With Locally Advanced or Metastatic Non-Small Cell Lung Cancer Previously Failed Platinum-containing Chemotherapy Regimens [NCT05673590] | Phase 3 | 612 participants (Anticipated) | Interventional | 2023-05-12 | Recruiting |
| Phase 1/2a, Open-Label, Multicenter Study of Intramuscular PRL-02 Depot in Patients With Advanced Prostate Cancer [NCT04729114] | Phase 1/Phase 2 | 100 participants (Anticipated) | Interventional | 2021-06-14 | Recruiting |
| A Prospective Randomised Phase III Study Of Androgen Deprivation Therapy With Or Without Docetaxel With Or Without Local Radiotherapy With Or Without Abiraterone Acetate And Prednisone In Patients With Metastatic Hormone-Naïve Prostate Cancer [NCT01957436] | Phase 3 | 1,173 participants (Actual) | Interventional | 2013-11-13 | Active, not recruiting |
| Docetaxel With Rapid Hormonal Cycling as a Treatment for Patients With Prostate Cancer [NCT00587431] | Phase 2 | 102 participants (Actual) | Interventional | 2003-07-31 | Completed |
| A Randomized, Phase 3, Open-label Study to Evaluate SGN-B6A Compared With Docetaxel in Adult Subjects With Previously Treated Non-small Cell Lung Cancer [NCT06012435] | Phase 3 | 560 participants (Anticipated) | Interventional | 2023-11-30 | Not yet recruiting |
| A Phase 3, Randomized, Double-blind Study of Pembrolizumab (MK-3475) Plus Docetaxel Plus Prednisone Versus Placebo Plus Docetaxel Plus Prednisone in Participants With Chemotherapy-naïve Metastatic Castration-Resistant Prostate Cancer (mCRPC) Who Have Prog [NCT03834506] | Phase 3 | 1,030 participants (Actual) | Interventional | 2019-05-02 | Completed |
| 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 2 | 128 participants (Anticipated) | Interventional | 2010-07-09 | Active, 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 3 | 1,560 participants (Anticipated) | Interventional | 2018-08-01 | Recruiting |
| A Randomized, Muticenter Double-blind Phase III Study of Neoadjuvant Pyrotinib Plus Trastuzumab and Docetaxel Compared With Placebo Plus Trastuzumab and Docetaxel in Women With HER2 Positive Early Stage or Locally Advanced Breast Cancer [NCT03588091] | Phase 3 | 355 participants (Actual) | Interventional | 2018-07-24 | Active, not recruiting |
| A Pilot Study of Raltegravir and Cisplatin in Squamous Cell Carcinoma of the Head and Neck [NCT01275183] | Early Phase 1 | 5 participants (Actual) | Interventional | 2010-12-31 | Completed |
| Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After the Same-Day, Varying Dosing Time Schedules of Eflapegrastim Administration in Patients With Breast-Cancer Receiving Docetaxel and Cyclophosphamide [NCT04187898] | Phase 1 | 90 participants (Anticipated) | Interventional | 2020-03-11 | Recruiting |
| An Open Label, Randomized Phase 3 Clinical Trial of Nivolumab vs Therapy of Investigator's Choice in Recurrent or Metastatic Platinum-refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN) [NCT02105636] | Phase 3 | 361 participants (Actual) | Interventional | 2014-05-29 | Completed |
| A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus the Combination of Trastuzumab Plus Docetaxel as First-Line Treatment of Patients With Her2-Positive Progressive Or Recurrent Locally [NCT02144012] | Phase 3 | 49 participants (Actual) | Interventional | 2014-06-30 | Terminated |
| A Phase 2, Multicenter, Randomized Study to Evaluate the Safety and Efficacy of Viagenpumatucel-L (HS-110) in Combination With Low Dose (Metronomic) Cyclophosphamide Versus Chemotherapy Alone in Patients With Non-Small Cell Lung Adenocarcinoma After Failu [NCT02117024] | Phase 2 | 66 participants (Actual) | Interventional | 2014-07-31 | Terminated(stopped due to Sponsor Decision; strategic - based on changing treatment landscape) |
| A Phase 1/2 Open-Label, Dose-Escalation and Clinical Response Study of Quaratusugene Ozeplasmid in Combination With Pembrolizumab Versus Docetaxel With or Without Ramucirumab in Patients With Previously Treated Non-Small Cell Lung Cancer [NCT05062980] | Phase 1/Phase 2 | 180 participants (Anticipated) | Interventional | 2022-03-30 | Recruiting |
| An Open-label, Multicentre, Phase IIIb Study With Intravenous Administration of Pertuzumab, Subcutaneous Trastuzumab, and a Taxane in Patients With HER2-positive Metastatic Breast Cancer [NCT02019277] | Phase 3 | 50 participants (Actual) | Interventional | 2013-12-05 | Completed |
| A Randomised, Double-blind, Parallel Group, Equivalence, Multicentre Phase III Trial to Compare the Efficacy, Safety and Pharmacokinetics of HD201 to Herceptin® in Patients With HER2+ Early Breast Cancer [NCT03013504] | Phase 3 | 503 participants (Actual) | Interventional | 2018-02-19 | Completed |
| Phase II Trial of Magrolimab and Cetuximab With Pembrolizumab or Docetaxel for Recurrent/Metastatic Head Neck Squamous Cell Carcinoma [NCT06046482] | Phase 2 | 57 participants (Anticipated) | Interventional | 2023-11-28 | Recruiting |
| 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 2 | 116 participants (Anticipated) | Interventional | 2023-09-20 | Recruiting |
| A Phase III, Randomized, Controlled, Open-label, Multicenter, Global Study of Capmatinib Versus SoC Docetaxel Chemotherapy in Previously Treated Patients With EGFR wt, ALK Negative, Locally Advanced or Metastatic (Stage IIIB/IIIC or IV) NSCLC Harboring ME [NCT04427072] | Phase 3 | 22 participants (Actual) | Interventional | 2020-09-25 | Completed |
| A Phase III, Multicenter, Randomized, Open-label Study of Oral LDK378 Versus Standard Chemotherapy in Adult Patients With ALK-rearranged (ALK-positive) Advanced Non-small Cell Lung Cancer Who Have Been Treated Previously With Chemotherapy (Platinum Double [NCT01828112] | Phase 3 | 231 participants (Actual) | Interventional | 2013-06-28 | Completed |
| 4 Cycles Of Neoadjuvant Chemotherapy Plus Concurrent Chemoradiation Versus Concurrent Chemoradiation Alone In Patients With Stage N2-3 Nasopharyngeal Carcinoma: A Phase 3 Multicenter Randomised Controlled Trial [NCT02512315] | Phase 3 | 192 participants (Anticipated) | Interventional | 2015-08-31 | Recruiting |
| 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 2 | 1,460 participants (Actual) | Interventional | 2014-04-07 | Active, not recruiting |
| A Phase 3, Randomized Study to Evaluate Plinabulin Versus Pegfilgrastim in the Prevention of Severe Neutropenia in Breast Cancer Patients Receiving Myelosuppressive Chemotherapy With Docetaxel, Doxorubicin, and Cyclophosphamide (TAC) (Protective 2) [NCT03294577] | Phase 3 | 221 participants (Actual) | Interventional | 2019-10-23 | Active, not recruiting |
| A Phase III Clinical Study to Compare the Combination Therapy of Eribulin Mesylate + Pertuzumab + Trastuzumab With Paclitaxel or Docetaxel + Pertuzumab + Trastuzumab (EMERALD) [NCT03264547] | Phase 3 | 480 participants (Anticipated) | Interventional | 2017-08-28 | Recruiting |
| A Pilot Study of Molecular Profile-Directed Chemotherapy for Metastatic HER2(-) Esophagogastric Adenocarcinoma [NCT02358863] | | 13 participants (Actual) | Interventional | 2015-02-28 | Terminated(stopped due to Issues with recruitment.) |
| A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab (Anti-PD-L1 Antibody) Compared With Docetaxel in Patients With Non-Small Cell Lung Cancer After Failure With Platinum Containing Chemotherapy [NCT02008227] | Phase 3 | 1,225 participants (Actual) | Interventional | 2014-03-11 | Completed |
| A Multi-center, Non-randomized, Three-cohort, Phase II Trial of a Modified Triplet Combination of Docetaxel, Oxaliplatin and Fluorouracil for Gastric Cancer With Peritoneal Carcinomatosis and Inoperable Malignant Bowel Obstruction [NCT04840264] | Phase 2 | 79 participants (Anticipated) | Interventional | 2022-01-07 | 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 3 | 1,052 participants (Actual) | Interventional | 2007-12-06 | Active, not recruiting |
| A Phase II Study of Capecitabine and Docetaxel in Previously Untreated Advanced Non-Small Cell Lung Cancer Patients [NCT00201825] | Phase 2 | 29 participants (Actual) | Interventional | 2004-12-31 | Completed |
| A Prospective Study of Savolitinib Plus Docetaxel in Pretreated EGFR/ALK/ROS1/MET ex14m-wildtype Advanced NSCLC Patients With MET Overexpression (FirstMET) [NCT05777278] | Phase 1/Phase 2 | 29 participants (Anticipated) | Interventional | 2023-07-26 | Recruiting |
| 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 2 | 28 participants (Actual) | Interventional | 2020-06-01 | Completed |
| A Randomized Phase 3 Study of MRTX849 Versus Docetaxel in Patients With Previously Treated Non-Small Cell Lung Cancer With KRAS G12C Mutation [NCT04685135] | Phase 3 | 450 participants (Anticipated) | Interventional | 2021-04-01 | Recruiting |
| A Randomized Phase III Non-inferiority Study of Induction Chemotherapy Followed by IMRT Alone Versus Induction Chemotherapy Followed by IMRT Plus Concurrent Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma [NCT02434614] | Phase 3 | 440 participants (Actual) | Interventional | 2015-03-31 | Active, not recruiting |
| A Multicenter, Randomized, Double-Blind, Parallel-Controlled Phase Ⅲ Clinical Study to Compare the Efficacy and Safety of SYSA1901 vs Pertuzumab (Perjeta®) in the Neoadjuvant Therapy of HER2-Positive Breast Cancer [NCT05720026] | Phase 3 | 560 participants (Anticipated) | Interventional | 2023-01-09 | Recruiting |
| Phase II Study of Dose Dense Carboplatin and Taxotere With Herceptin As Primary Systemic Therapy in Breast Cancer [NCT00232479] | Phase 2 | 48 participants (Actual) | Interventional | 2005-09-30 | Completed |
| A Randomized Crossover, Phase II Clinical Trial of MK-3475 in Combination With Docetaxel Versus Docetaxel Alone in Patients With Non-Small Cell Lung Cancer (NSCLC) Previously Treated. [NCT02574598] | Phase 2 | 78 participants (Actual) | Interventional | 2016-06-30 | Completed |
| A Multicenter, Open-label, Randomized Phase II Study to Evaluate the Efficacy of AUY922 vs Pemetrexed or Docetaxel in NSCLC Patients With EGFR Mutations Who Have Progressed on Prior EGFR TKI Treatment [NCT01646125] | Phase 2 | 59 participants (Actual) | Interventional | 2012-11-23 | Terminated(stopped due to An interim analysis was conducted in May-2014. Upon review of the data, the committee recommended study termination due to futility.) |
| TIGER-3: A Phase 3, Open-label, Multicenter, Randomized Study of Oral Rociletinib (CO-1686) Monotherapy Versus Single-agent Cytotoxic Chemotherapy in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC) After Failure of at Least 1 Previous EGFR-di [NCT02322281] | Phase 3 | 149 participants (Actual) | Interventional | 2015-02-28 | Terminated(stopped due to Sponsor discontinued development of CO-1686 for NSCLC) |
| Phase 2, Open-Label, Dose-Ranging Study of SPI-2012 (HM10460A) or Pegfilgrastim Use for the Management of Neutropenia in Patients With Breast Cancer Who Are Candidates for Adjuvant and Neoadjuvant Chemotherapy With the Docetaxel + Cyclophosphamide (TC) Re [NCT01724866] | Phase 2 | 148 participants (Actual) | Interventional | 2013-03-25 | Completed |
| A Phase II/III Randomized Trial of Two Doses of MK-3475 (SCH900475) Versus Docetaxel in Previously Treated Subjects With Non-Small Cell Lung Cancer [NCT01905657] | Phase 2/Phase 3 | 1,034 participants (Actual) | Interventional | 2013-08-09 | Completed |
| A Phase I and Randomized Phase II Multicenter Study of Cabozantinib (XL184) Plus Docetaxel and Prednisone in Metastatic Castrate Resistant Prostate Cancer [NCT01683994] | Phase 1/Phase 2 | 49 participants (Actual) | Interventional | 2012-09-07 | Completed |
| A Phase I, Open-label Clinical Trial to Evaluate Safety, Tolerability, Antitumor Activities and Pharmacokinetics of IN10018 as Mono or Combination Therapy in Locally Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma [NCT05327231] | Phase 1 | 33 participants (Actual) | Interventional | 2020-07-09 | Completed |
| Dose-Dense Induction/Neoadjuvant Chemotherapy in the Treatment of Patients With Locally Advanced Non-Small Cell Lung Cancer With Additional Genomic Analyses to Identify Signatures Predictive of Chemotherapy Response. [NCT02157116] | Phase 2 | 13 participants (Actual) | Interventional | 2006-05-31 | Terminated(stopped due to Insufficient accrual to meet analysis goals) |
| [information is prepared from clinicaltrials.gov, extracted Sep-2024] |
| Trial | Outcome |
|---|
| NCT00003782 (1) [back to overview] | Overall Survival |
| NCT00004888 (6) [back to overview] | Progression-Free Survival |
| NCT00004888 (6) [back to overview] | Overall Survival |
| NCT00004888 (6) [back to overview] | Duration of Response |
| NCT00004888 (6) [back to overview] | Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event |
| NCT00004888 (6) [back to overview] | Summary of Left Ventricular Ejection Fraction Values |
| NCT00004888 (6) [back to overview] | Best Overall Response Using Eastern Cooperative Group Solid Tumor Response Criteria. |
| NCT00005908 (4) [back to overview] | Overall Clinical Response Rate |
| NCT00005908 (4) [back to overview] | Number of Participants, e.g. Responders and Non-responders With a Percent Change in Expression Patterns After Chemotherapy With Changes in Expression Patterns After Chemotherapy in Preclinical Models |
| NCT00005908 (4) [back to overview] | Complementary Deoxyribonucleic Acid (cDNA) Expression |
| NCT00005908 (4) [back to overview] | Number of Participants With Adverse Events |
| NCT00017563 (1) [back to overview] | Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence. |
| NCT00021255 (3) [back to overview] | Percentage of Participants With Disease Free Survival at 5 Years |
| NCT00021255 (3) [back to overview] | Percentage of Participants With Disease Free Survival at 10 Years |
| NCT00021255 (3) [back to overview] | Overall Survival- Percentage of Participants Who Survived at 10 Years |
| NCT00024167 (2) [back to overview] | Overall Survival From Randomization |
| NCT00024167 (2) [back to overview] | Overall Survival From Registration |
| NCT00041067 (4) [back to overview] | Progression-free Survival |
| NCT00041067 (4) [back to overview] | Response Rate (Complete and Partial, Confirmed and Unconfirmed) |
| NCT00041067 (4) [back to overview] | Toxicity |
| NCT00041067 (4) [back to overview] | Survival at 1 Year |
| NCT00042939 (5) [back to overview] | Epidermal Growth Factor Receptor (EGFR) Status |
| NCT00042939 (5) [back to overview] | Proportion of Patients With Thromboembolic Events |
| NCT00042939 (5) [back to overview] | Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria) |
| NCT00042939 (5) [back to overview] | Progression-free Survival |
| NCT00042939 (5) [back to overview] | Overall Survival |
| NCT00050167 (1) [back to overview] | Percentage of Participants With Reoccurrence |
| NCT00054275 (3) [back to overview] | Progression Free Survival(PFS) |
| NCT00054275 (3) [back to overview] | Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000 |
| NCT00054275 (3) [back to overview] | Overall Survival as of 2008 |
| NCT00062439 (5) [back to overview] | Adverse Events |
| NCT00062439 (5) [back to overview] | Response |
| NCT00062439 (5) [back to overview] | Progression-Free Survival at 3 Years |
| NCT00062439 (5) [back to overview] | Overall Survival |
| NCT00062439 (5) [back to overview] | Feasibility of Treating Patients With Stage IIB/IIIB Pancoast Tumors With a Regimen of Cisplatin and Etoposide Plus Concurrent Radiotherapy Followed by Surgical Resection Followed by Consolidation Therapy With Docetaxel. |
| NCT00063934 (4) [back to overview] | Clinical Imaging Responses |
| NCT00063934 (4) [back to overview] | Number of Participants With Pathologic Complete Response (pCR) |
| NCT00063934 (4) [back to overview] | Number of Participant With Toxicities |
| NCT00063934 (4) [back to overview] | Bcl-2 Expression in Breast Cancer Tissue |
| NCT00065182 (5) [back to overview] | Number of Participants With Grade 1, 2, 3 or 4 Hematologic Toxicities |
| NCT00065182 (5) [back to overview] | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT00065182 (5) [back to overview] | Median Time of Overall Survival |
| NCT00065182 (5) [back to overview] | Number of Participants With Clinically Significant Abnormal Vital Signs Data |
| NCT00065182 (5) [back to overview] | Number of Participants With Grade 3 or 4 Clinical Chemical Toxicities |
| NCT00066677 (4) [back to overview] | Number of Participants With Thromboembolic Events |
| NCT00066677 (4) [back to overview] | Overall Survival |
| NCT00066677 (4) [back to overview] | Progression-free Survival |
| NCT00066677 (4) [back to overview] | Objective Response Rate |
| 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. |
| NCT00068341 (5) [back to overview] | Pathologic Nodal Status |
| NCT00069160 (6) [back to overview] | Geometric Mean of Maximum Concentration of the Drug (Cmax) |
| NCT00069160 (6) [back to overview] | Clinical Response Rate |
| NCT00069160 (6) [back to overview] | Percent Increase in Sestamibi Area Under Curve (AUC) in Liver After Tariquidar |
| NCT00069160 (6) [back to overview] | Percent Increase in Sestamibi Area Under Curve (AUC) in Tumor Tissue |
| NCT00069160 (6) [back to overview] | The Number of Participants With Adverse Events. |
| NCT00069160 (6) [back to overview] | Geometric Mean of Area Under Curve (AUC0)-24 |
| NCT00073983 (2) [back to overview] | Objective Response Rate |
| NCT00073983 (2) [back to overview] | Toxicity as Assessed by NCI CTCAE v3.0 |
| NCT00076024 (5) [back to overview] | Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind) |
| NCT00076024 (5) [back to overview] | Percentage of Participants With Objective Response (OR) for Phase 2 (Open-label) |
| NCT00076024 (5) [back to overview] | Duration of Response (DR) for Phase 2 (Double-blind) |
| NCT00076024 (5) [back to overview] | Duration of Response (DR) for Phase 2 (Open-label) |
| NCT00076024 (5) [back to overview] | Time to Tumor Progression (TTP) |
| NCT00077857 (7) [back to overview] | Number of Participants With Adverse Events and Serious Adverse Events |
| NCT00077857 (7) [back to overview] | Time to Overall Response |
| NCT00077857 (7) [back to overview] | Time to Progression of Disease or Death |
| NCT00077857 (7) [back to overview] | Percentage of Participants With Best Overall Response Being Complete Response (CR) or Partial Response (PR) |
| NCT00077857 (7) [back to overview] | Overall Survival |
| NCT00077857 (7) [back to overview] | Duration of Overall Response |
| NCT00077857 (7) [back to overview] | Time to Treatment Failure |
| NCT00084318 (6) [back to overview] | Disease-free Survival |
| NCT00084318 (6) [back to overview] | Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4) |
| NCT00084318 (6) [back to overview] | Overall Survival |
| NCT00084318 (6) [back to overview] | Frequency of Other Acute and Late Toxicity |
| NCT00084318 (6) [back to overview] | Treatment Tolerance |
| NCT00084318 (6) [back to overview] | Local-regional Control |
| NCT00086957 (5) [back to overview] | Objective Response Rate |
| NCT00086957 (5) [back to overview] | Overall Survival |
| NCT00086957 (5) [back to overview] | Progression-free Survival |
| NCT00086957 (5) [back to overview] | Number of Participants With at Least One Dose Limiting Toxicity in Phase I |
| NCT00086957 (5) [back to overview] | Recommended Phase II Dose |
| NCT00088907 (3) [back to overview] | Overall Survival |
| NCT00088907 (3) [back to overview] | Overall Response Rate |
| NCT00088907 (3) [back to overview] | Time to Progression |
| NCT00089479 (10) [back to overview] | Disease Free Survival Including Any New Cancer as Event [Number of Events] |
| NCT00089479 (10) [back to overview] | Disease Free Survival [Number of Events] |
| NCT00089479 (10) [back to overview] | Breast Cancer Free Survival [Number of Events] |
| NCT00089479 (10) [back to overview] | Overall Survival [Time to Event] |
| NCT00089479 (10) [back to overview] | Disease Free Survival Including New Primary Breast Cancer as Event [Time to Event |
| NCT00089479 (10) [back to overview] | Disease Free Survival Including Any New Cancer as Event [Time to Event] |
| NCT00089479 (10) [back to overview] | Breast Cancer Free Survival [Time to Event] |
| NCT00089479 (10) [back to overview] | Disease Free Survival [Time to Event] |
| NCT00089479 (10) [back to overview] | Overall Survival [Number of Events] |
| NCT00089479 (10) [back to overview] | Disease Free Survival Including New Primary Breast Cancer as Event [Number of Events] |
| NCT00089609 (6) [back to overview] | Number of Participants Who Died After a Follow Up of 34 Months Following Treatment |
| NCT00089609 (6) [back to overview] | Number of Participants With a Significant Increase in Circulating Apoptotic Endothelial Cell (CAEC) Level |
| NCT00089609 (6) [back to overview] | Number of Participants With Adverse Events |
| NCT00089609 (6) [back to overview] | Time to Progression Using Bubley Criteria |
| NCT00089609 (6) [back to overview] | Number of Participants Who Had a Prostate-specific Antigen (PSA) Response |
| NCT00089609 (6) [back to overview] | Disease Progression by Clinical and Radiographic Criteria Without the Use of Prostate-Specific Antigen (PSA) |
| NCT00090610 (5) [back to overview] | Quality of Life |
| NCT00090610 (5) [back to overview] | Median Overall Survival |
| NCT00090610 (5) [back to overview] | Progression-free Survival (PFS) |
| NCT00090610 (5) [back to overview] | Recurrence-Free Survival |
| NCT00090610 (5) [back to overview] | Objective Response Rate |
| NCT00091442 (3) [back to overview] | Time to Progression |
| NCT00091442 (3) [back to overview] | Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) |
| NCT00091442 (3) [back to overview] | Overall Survival |
| NCT00093795 (5) [back to overview] | Disease-free Survival: Any Recurrence, Contralateral Breast Cancer, Second Primary Cancer, Death From Any Cause Prior to Recurrence or Second Primary Cancer |
| NCT00093795 (5) [back to overview] | Distant Recurrence-free Interval: the Time to Distant Disease Recurrence Only |
| NCT00093795 (5) [back to overview] | Recurrence-free Interval: Time to First Local, Regional, or Distant Recurrence |
| NCT00093795 (5) [back to overview] | Overall Survival |
| NCT00093795 (5) [back to overview] | Toxicity |
| NCT00095199 (8) [back to overview] | Proportion of Randomized Participants With the Best Overall Response (OR) of Partial Response (PR) or Complete Response (CR) (Overall Response Rate [ORR]) |
| NCT00095199 (8) [back to overview] | Duration of Overall Response (OR) |
| NCT00095199 (8) [back to overview] | Time to Symptomatic Progression |
| NCT00095199 (8) [back to overview] | Overall Survival (OS) |
| NCT00095199 (8) [back to overview] | Percentage of Participants With Symptomatic Response (Symptom Response Rates) Using the Lung Cancer Subscale (LCS) Scores of Functional Assessment of Cancer Therapy for Participants With Lung Cancer (FACT-L) |
| NCT00095199 (8) [back to overview] | Progression Free Survival (PFS) |
| NCT00095199 (8) [back to overview] | Proportion of Randomized Participants With Best Overall Response (OR) of Partial Response (PR), Complete Response (CR), or Stable Disease (SD) |
| NCT00095199 (8) [back to overview] | Number of Participants With Common Toxicity Criteria (CTC) Grade 3 or 4 Toxicities |
| NCT00095875 (2) [back to overview] | Overall Survival |
| 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 |
| NCT00110214 (4) [back to overview] | Proportion of Participants Who Experience (Maximum) Grade 3 or Higher Toxicities |
| NCT00110214 (4) [back to overview] | Proportion of Participants Who Experienced at Least a 50% Post-therapy PSA (Prostate-Specific Antigen) Decline |
| NCT00110214 (4) [back to overview] | Overall Survival |
| NCT00110214 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT00112294 (15) [back to overview] | Median Number of Months of Progression-free Survival (PFS) |
| NCT00112294 (15) [back to overview] | Median Change From Baseline in Symptoms, by Time Point |
| NCT00112294 (15) [back to overview] | Number of Participants Experiencing Other Significant AEs: Acneform Rash |
| NCT00112294 (15) [back to overview] | Median Number of Months to Response |
| NCT00112294 (15) [back to overview] | Median Number of Months of Survival |
| 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 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] | Number of Participants With Improvement of Symptoms |
| 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 With Complete Response (CR) or Partial Response (PR) |
| NCT00112294 (15) [back to overview] | Number of Participants Experiencing Other Significant AEs: Infusion Reaction |
| NCT00112294 (15) [back to overview] | Number of Participants Experiencing Other Significant AEs: Cardiac AEs |
| NCT00112294 (15) [back to overview] | Median Number of Months of Response |
| NCT00114218 (2) [back to overview] | Incidence of Adverse Effects That Are Grade 3 or Greater as Assessed by Common Terminology Criteria for Adverse Events Version 3.0 |
| NCT00114218 (2) [back to overview] | Percentage of Patients With Objective Tumor Response Rate (Either Complete Response (CR) or Partial Response (PR) Using RECIST Version 1.0 |
| NCT00116142 (5) [back to overview] | Number of Participants With Late Adverse Events, Any Grade and Attribution |
| NCT00116142 (5) [back to overview] | Number of Participants With Acute Adverse Events |
| NCT00116142 (5) [back to overview] | 10-Year Restricted Mean Survival Time for Overall Survival |
| NCT00116142 (5) [back to overview] | 10-year Biochemical Recurrence (PSA Failure) |
| NCT00116142 (5) [back to overview] | 10-year Prostate Cancer Mortality |
| NCT00117572 (13) [back to overview] | Quality of Life (McMaster) |
| NCT00117572 (13) [back to overview] | Quality of Life (McMaster) |
| NCT00117572 (13) [back to overview] | Quality of Life (Normalcy of Diet) |
| NCT00117572 (13) [back to overview] | Quality of Life (Speech) |
| NCT00117572 (13) [back to overview] | Quality of Life (FACT H&N) |
| NCT00117572 (13) [back to overview] | Overall Survival: Time From Randomization to Death From Any Cause |
| NCT00117572 (13) [back to overview] | Recurrence Free Survival: Time From Randomization to Local/Regional/Distant Recurrence or Death From Any Cause |
| NCT00117572 (13) [back to overview] | Quality of Life (Normalcy of Diet) |
| NCT00117572 (13) [back to overview] | Distant Failure-free Survival (DFFS): Time From Randomization to Distant Recurrence or Death From Any Cause |
| NCT00117572 (13) [back to overview] | Failure Pattern (Distant Recurrence) |
| NCT00117572 (13) [back to overview] | Failure Pattern (Local/Regional Recurrence) |
| NCT00117572 (13) [back to overview] | Quality of Life (Speech) |
| NCT00117572 (13) [back to overview] | Quality of Life (FACT H&N) |
| NCT00118131 (4) [back to overview] | Overall Tumor Response Rate |
| NCT00118131 (4) [back to overview] | 1-year Survival Rate |
| NCT00118131 (4) [back to overview] | Time to Progressive Disease |
| NCT00118131 (4) [back to overview] | Median Survival Time |
| NCT00121992 (8) [back to overview] | Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup |
| NCT00121992 (8) [back to overview] | Disease-free Survival (DFS) Events |
| NCT00121992 (8) [back to overview] | Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup |
| NCT00121992 (8) [back to overview] | The Number of Participants Who Experienced Adverse Events (AE) |
| NCT00121992 (8) [back to overview] | Overall Survival (OS) |
| NCT00121992 (8) [back to overview] | Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup |
| NCT00121992 (8) [back to overview] | Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup |
| NCT00121992 (8) [back to overview] | Best Score During Study for Global Health Status Scale |
| NCT00127933 (6) [back to overview] | Percentage of Participants With Complete Pathological Response in the Primary Breast Tumor at the Time of Definitive Surgery |
| NCT00127933 (6) [back to overview] | Participants With Overall Survival |
| NCT00127933 (6) [back to overview] | Participants With Disease-Free Survival |
| NCT00127933 (6) [back to overview] | Percentage of Participants Assessed for Pathological Complete Response (pCR) Plus Near Complete (npCR) in Primary Breast Tumor at Time of Definitive Surgery |
| NCT00127933 (6) [back to overview] | Percentage of Participants With Local Recurrence |
| NCT00127933 (6) [back to overview] | Percentage of Participants With Overall Clinical Response (Complete Response (CR) Plus Partial Response (PR)) |
| NCT00129376 (3) [back to overview] | Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining) |
| NCT00129376 (3) [back to overview] | Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining) |
| NCT00129376 (3) [back to overview] | Pathological Complete Response (pCR) Rate |
| NCT00129935 (4) [back to overview] | Number of Participants With Disease-free Survival (DFS) Event |
| NCT00129935 (4) [back to overview] | The Number of Participants Who Experienced Adverse Events (AE) |
| NCT00129935 (4) [back to overview] | Quality of Life Questionnaire: Time to Taking Off the Wig |
| NCT00129935 (4) [back to overview] | Number of Participants With Overall Survival (OS) Event |
| NCT00130780 (1) [back to overview] | The Primary Goal of This Study is to Show That the Addition of Bevacizumab to Cisplatin-based Chemotherapy in the Neoadjuvant Setting for Non-squamous Cell Carcinomas Improves Therapeutic Response/Outcome Assessment. |
| NCT00132301 (1) [back to overview] | Number of Participants With Progression-Free Survival |
| NCT00134056 (7) [back to overview] | Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer. |
| NCT00134056 (7) [back to overview] | Number of Patients With a Change in Functional Status |
| NCT00134056 (7) [back to overview] | Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer. |
| NCT00134056 (7) [back to overview] | Compare Pain Progression Between the Two Study Arms. |
| NCT00134056 (7) [back to overview] | Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI) |
| NCT00134056 (7) [back to overview] | Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm. |
| NCT00134056 (7) [back to overview] | Compare Qualitative and Quantitative Toxicity Between the Two Study Arms |
| NCT00137436 (13) [back to overview] | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR2 |
| NCT00137436 (13) [back to overview] | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR3 |
| NCT00137436 (13) [back to overview] | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFR2 |
| NCT00137436 (13) [back to overview] | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Clinical Benefit Response (CBR): VEGFC |
| NCT00137436 (13) [back to overview] | Ratio to Baseline (Bsl) in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFC |
| NCT00137436 (13) [back to overview] | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf): Pain Interference (Questions 7A Through 7G) |
| NCT00137436 (13) [back to overview] | Time to PSA Progression |
| NCT00137436 (13) [back to overview] | Percentage of Participants With Prostate Specific Antigen (PSA) Response |
| NCT00137436 (13) [back to overview] | Percentage of Participants With Objective Response Rate (ORR) |
| NCT00137436 (13) [back to overview] | Duration of PSA Response (DPR) |
| NCT00137436 (13) [back to overview] | Change From Baseline in Modified Brief Pain Inventory-Short Form (mBPI-sf) : Pain Intensity (Questions 2-5) |
| NCT00137436 (13) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale) |
| NCT00137436 (13) [back to overview] | Ratio to Baseline in Median Levels of Soluble Protein Biomarkers by Prostate Specific Antigen (PSA) Response: VEGFR3 |
| NCT00145418 (4) [back to overview] | Response Rate |
| NCT00145418 (4) [back to overview] | Duration of Response |
| NCT00145418 (4) [back to overview] | Safety Objective is to Describe the Safety Profile of 1st Line Treatment by Recording Grade 3 and 4 Adverse Events Experienced by Participants in This Trial. |
| NCT00145418 (4) [back to overview] | Time to Progression |
| NCT00148122 (3) [back to overview] | Probability of Progression Free Survival |
| NCT00148122 (3) [back to overview] | Frequency of Grade III/IV Toxicities Experienced by Participants |
| NCT00148122 (3) [back to overview] | Overall Response Rate at 4 Months |
| 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 |
| NCT00149214 (5) [back to overview] | Disease-free Survival |
| NCT00149214 (5) [back to overview] | Number of Patients With Histologically Negative Axillary Lymph Node Status at Surgery |
| NCT00149214 (5) [back to overview] | Number of Participants With a Pathological Complete Response |
| NCT00149214 (5) [back to overview] | Number of Participants With a Clinical Tumor Response After the First Sequence of Chemotherapy |
| NCT00149214 (5) [back to overview] | Number of Participants With a Clinical Tumor Response After the Second Sequence of Chemotherapy |
| NCT00177255 (2) [back to overview] | Overall Survival |
| NCT00177255 (2) [back to overview] | Overall Response Rate |
| NCT00179309 (2) [back to overview] | Progression-free Survival (PFS) |
| NCT00179309 (2) [back to overview] | Number of Participants With Adverse Events |
| NCT00183794 (2) [back to overview] | Tumor Response Type: CR, PR, SD or PD |
| NCT00183794 (2) [back to overview] | Median Time to Progression (Months) |
| NCT00183872 (2) [back to overview] | Progression Free Survival |
| NCT00183872 (2) [back to overview] | Objective Response (Complete, Partial, Stable and Progression) |
| NCT00184028 (2) [back to overview] | Tumor Response |
| NCT00184028 (2) [back to overview] | Number of Participants With Serious Adverse Events (SAEs) |
| NCT00189137 (2) [back to overview] | The Percentage of Patients Alive Without Disease at 2 Years |
| NCT00189137 (2) [back to overview] | Percentage of Patients Hospitalized in Each Arm. |
| NCT00191139 (5) [back to overview] | Overall Survival |
| NCT00191139 (5) [back to overview] | 2-Year Survival |
| NCT00191139 (5) [back to overview] | Number of Patients With Overall Tumor Response |
| NCT00191139 (5) [back to overview] | Lung Cancer Symptom Scale (LCSS) Assessment Post-randomization |
| NCT00191139 (5) [back to overview] | Progression-Free Survival |
| NCT00191152 (13) [back to overview] | Duration of Response (Crossover Treatment) |
| NCT00191152 (13) [back to overview] | Best Overall Response (Initial Treatment) |
| NCT00191152 (13) [back to overview] | Duration of Response (Initial Treatment) |
| NCT00191152 (13) [back to overview] | Progression-Free Survival (Crossover Treatment) |
| NCT00191152 (13) [back to overview] | Overall Survival |
| NCT00191152 (13) [back to overview] | Progression-Free Survival (Initial Treatment) |
| NCT00191152 (13) [back to overview] | Summary of Changes in Rotterdam Symptom Checklist by Treatment (Crossover Treatment) |
| NCT00191152 (13) [back to overview] | Time to Disease Progression (Initial Treatment) |
| NCT00191152 (13) [back to overview] | Time to Disease Progression (Crossover Treatment) |
| NCT00191152 (13) [back to overview] | Summary of Changes in Rotterdam Symptom Checklist (RSCL) by Treatment (Initial Treatment) |
| NCT00191152 (13) [back to overview] | Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Initial Treatment) |
| NCT00191152 (13) [back to overview] | Summary of Changes in Karnofsky Performance Status (KPS) by Treatment (Crossover Treatment) |
| NCT00191152 (13) [back to overview] | Best Overall Response (Crossover Treatment) |
| NCT00193037 (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. |
| NCT00193037 (2) [back to overview] | Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment |
| NCT00193050 (3) [back to overview] | Time to Treatment Failure (TTF) |
| NCT00193050 (3) [back to overview] | Overall Survival (OS) |
| NCT00193050 (3) [back to overview] | Pathologic Complete Response (pCR) |
| NCT00193128 (3) [back to overview] | Overall Survival (OS) |
| NCT00193128 (3) [back to overview] | Disease-Free Survival (DFS) |
| NCT00193128 (3) [back to overview] | Pathologic Complete Response Rate (PCRR), the Percentage of Patients Who Have No Evidence of Cancer in Their Surgical Specimen Following Surgery |
| NCT00193180 (3) [back to overview] | Overall Response Rate (ORR) |
| NCT00193180 (3) [back to overview] | Overall Survival (OS) |
| NCT00193180 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT00193427 (4) [back to overview] | Overall Survival (OS) |
| NCT00193427 (4) [back to overview] | Overall Response Rate (ORR) |
| NCT00193427 (4) [back to overview] | Pathologic Complete Response Rate |
| NCT00193427 (4) [back to overview] | Progression Free Survival (PFS) |
| NCT00193453 (3) [back to overview] | Response Duration |
| NCT00193453 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT00193453 (3) [back to overview] | Overall Clinical Response Rate |
| NCT00201825 (3) [back to overview] | Determine Objective Response Rate |
| NCT00201825 (3) [back to overview] | Time to Tumor Progression |
| NCT00201825 (3) [back to overview] | One Year Survival |
| NCT00203502 (5) [back to overview] | To Measure the Change in Left Ventricular Ejection Fraction (LVEF) From Baseline |
| NCT00203502 (5) [back to overview] | Percentage of Participants With Pathologic Complete Response (pCR) Among Those With Triple Negative Breast Cancer |
| NCT00203502 (5) [back to overview] | Percentage of Participants With Pathological Complete Response. |
| NCT00203502 (5) [back to overview] | Number of Participants With Clinical Complete Response in Breast and the Axillary Lymph Nodes After the Completion of Chemotherapy and Bevacizumab. |
| NCT00203502 (5) [back to overview] | Percentage of Participants With Grade 3 or 4 Adverse Events |
| NCT00206518 (3) [back to overview] | Overall Survival |
| NCT00206518 (3) [back to overview] | Pathological Tumor Response to Neoadjuvant Chemotherapy (Taxotere and AC) |
| NCT00206518 (3) [back to overview] | Disease Relapse |
| NCT00209092 (2) [back to overview] | Long Term Follow up Data on Recurrence and Survival |
| NCT00209092 (2) [back to overview] | Number of Participants With Complete Pathologic Response Rate to Pre-operative Treatment in Arm A (Docetaxel for 4 Cycles Followed by Capecitabine for 4 Cycles) or Arm B (Docetaxel + Capecitabine for 8 Cycles) in Patients With Early Stage Breast Cancer. |
| NCT00215930 (3) [back to overview] | Best Disease Response After a Maximum of Six Cycles. |
| NCT00215930 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT00215930 (3) [back to overview] | Overall Survival (OS) |
| NCT00216125 (2) [back to overview] | Overall Survival |
| NCT00216125 (2) [back to overview] | Progression Free Survival |
| NCT00217581 (5) [back to overview] | Overall Survival |
| NCT00217581 (5) [back to overview] | Response Rate by RECIST Criteria |
| NCT00217581 (5) [back to overview] | Time to Progression |
| NCT00217581 (5) [back to overview] | Time to Treatment Failure |
| NCT00217581 (5) [back to overview] | Toxicity Profile |
| NCT00217672 (3) [back to overview] | Comparison of Response Rates, Duration of Response, and Overall Survival |
| NCT00217672 (3) [back to overview] | Comparison of Safety and Toxicity |
| NCT00217672 (3) [back to overview] | Antitumor Activity Based on Time to Tumor Progression (TTP). |
| NCT00225420 (2) [back to overview] | Biochemical Progression-free Survival (PFS) |
| NCT00225420 (2) [back to overview] | Number of Patients Experiencing Dose-Limiting Toxicities |
| NCT00226239 (5) [back to overview] | 2-year Overall Survival (OS) |
| NCT00226239 (5) [back to overview] | 3-year Overall Survival (OS) |
| NCT00226239 (5) [back to overview] | Objective Response Rate (ORR) |
| NCT00226239 (5) [back to overview] | Progression-free Survival (PFS) |
| NCT00226239 (5) [back to overview] | Quality of Life (QOL) |
| NCT00227721 (2) [back to overview] | Progression-free Survival |
| NCT00227721 (2) [back to overview] | Response Rate to the Combination of Gemcitabine and Docetaxel in Patients With Platinum Sensitive and Resistant Epithelial Ovarian or Peritoneal Cancer. |
| NCT00231465 (3) [back to overview] | Overall Response Rate (ORR) |
| NCT00231465 (3) [back to overview] | Overall Survival (OS) Rate |
| NCT00231465 (3) [back to overview] | Progression Free Survival (PFS) Rate |
| NCT00232479 (2) [back to overview] | Safety and Tolerability |
| NCT00232479 (2) [back to overview] | Number of Patients With Pathologic Complete Response (pCR) |
| NCT00236899 (9) [back to overview] | Overall Survival (OS) by Treatment Drug |
| NCT00236899 (9) [back to overview] | Overall Survival (OS) by Treatment Schedule |
| NCT00236899 (9) [back to overview] | Time to Progressive Disease (TTPD) by Treatment Drug |
| NCT00236899 (9) [back to overview] | Number of Participants With Serious and Nonserious Adverse Events (AEs) |
| NCT00236899 (9) [back to overview] | Time to Progressive Disease (TTPD) by Treatment Schedule |
| NCT00236899 (9) [back to overview] | Quality of Life (QOL) Using the Rotterdam Symptom Scale Checklist (RSSC) at Beginning of 3-Week or 4-Week Cycle |
| NCT00236899 (9) [back to overview] | Quality of Life (QOL) Using the Rotterdam Symptom Scale Checklist (RSSC) at 30-Day Post-therapy Visit |
| NCT00236899 (9) [back to overview] | Overall Response Rate(ORR) by Treatment Drug |
| NCT00236899 (9) [back to overview] | Overall Response Rate (ORR) by Treatment Schedule |
| 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. |
| 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 |
| NCT00248560 (4) [back to overview] | Survival |
| NCT00248560 (4) [back to overview] | Response (Complete Response [CR] + Partial Response [PR]) |
| NCT00248560 (4) [back to overview] | Response Duration |
| NCT00248560 (4) [back to overview] | Toxicity as Measured by Number and Grade of Adverse Events |
| NCT00251225 (3) [back to overview] | Overall Survival (OS) |
| NCT00251225 (3) [back to overview] | Overall Time To Progression (TTP) |
| NCT00251225 (3) [back to overview] | Prostate-Specific Antigen (PSA) Response Rate |
| NCT00253370 (3) [back to overview] | The Proportion of Patients With Objective Response (Complete Response or Partial Response) |
| NCT00253370 (3) [back to overview] | Progression-free Survival (PFS) |
| NCT00253370 (3) [back to overview] | Overall Survival (OS) |
| NCT00256282 (2) [back to overview] | Progression-free Survival (PFS) in Patients With AJCC Stage IV Metastatic Melanoma Treated With Docetaxel and Vinorelbine as First-line or Post-first Line (Salvage) Systemic Therapy |
| NCT00256282 (2) [back to overview] | Percentage of Patients Alive at One Year |
| NCT00258362 (2) [back to overview] | Percent of Patients Estimated to be Alive |
| NCT00258362 (2) [back to overview] | Percent of Patients Estimated to be Progression-Free and Alive |
| NCT00270894 (7) [back to overview] | Left Ventricular Ejection Fraction (LVEF) |
| NCT00270894 (7) [back to overview] | Frequency of Grade 3 or 4 Hematologic and Nonhematologic Toxicities |
| NCT00270894 (7) [back to overview] | Clinical Response Prior to Surgery |
| NCT00270894 (7) [back to overview] | Progression-free Survival (PFS) |
| NCT00270894 (7) [back to overview] | Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule |
| NCT00270894 (7) [back to overview] | Overall Survival (OS) |
| NCT00270894 (7) [back to overview] | Pathologic Response |
| NCT00271505 (3) [back to overview] | Disease Control Rate |
| NCT00271505 (3) [back to overview] | Overall Survival (OS)- 5 Years |
| NCT00271505 (3) [back to overview] | Time to Progression-Free Survival (PFS) |
| NCT00274456 (9) [back to overview] | Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts |
| NCT00274456 (9) [back to overview] | Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response |
| NCT00274456 (9) [back to overview] | Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator |
| NCT00274456 (9) [back to overview] | Participants With Treatment-Emergent, Treatment-Related Adverse Events |
| NCT00274456 (9) [back to overview] | Kaplan-Meier Estimates for Progression-free Survival (PFS) |
| NCT00274456 (9) [back to overview] | Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts |
| NCT00274456 (9) [back to overview] | Kaplan-Meier Estimate for Overall Survival (OS) |
| NCT00274456 (9) [back to overview] | Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression |
| NCT00274456 (9) [back to overview] | Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression |
| NCT00276549 (2) [back to overview] | Objective PSA Response Rate (Number of Patients With a PSA Response) |
| NCT00276549 (2) [back to overview] | Number of Patients With Measurable Soft Tissue Disease Will be Assessed Per Solid Tumor Response Criteria (RECIST). |
| NCT00276744 (1) [back to overview] | 6-month Overall Survival |
| NCT00280735 (4) [back to overview] | Toxicity in Patients Treated With This Regimen |
| NCT00280735 (4) [back to overview] | Progression Free Survival |
| NCT00280735 (4) [back to overview] | Overall Survival |
| NCT00280735 (4) [back to overview] | Number of Participants Who Completed Four Cycles of the Carboplatin/Docetaxel Regimen |
| NCT00281840 (2) [back to overview] | Response Rate |
| NCT00281840 (2) [back to overview] | Time to Progression |
| NCT00282087 (10) [back to overview] | Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS) |
| NCT00282087 (10) [back to overview] | Correlation Between Age and Tumor Response to Treatment (PFS) |
| NCT00282087 (10) [back to overview] | Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS) |
| NCT00282087 (10) [back to overview] | Tolerability/Toxicity of This Regimen |
| NCT00282087 (10) [back to overview] | Two-year Progression-free Survival Among Women Treated With This Adjuvant Regimen for High Risk Uterine LMS |
| NCT00282087 (10) [back to overview] | Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS) |
| NCT00282087 (10) [back to overview] | Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS) |
| NCT00282087 (10) [back to overview] | Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS) |
| NCT00282087 (10) [back to overview] | Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS) |
| NCT00282087 (10) [back to overview] | Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS) |
| NCT00283062 (4) [back to overview] | To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire |
| NCT00283062 (4) [back to overview] | Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE) |
| NCT00283062 (4) [back to overview] | Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression |
| NCT00283062 (4) [back to overview] | Median Overall Survival (OS) |
| NCT00288054 (5) [back to overview] | Progression-free Survival. |
| NCT00288054 (5) [back to overview] | Toxicity |
| NCT00288054 (5) [back to overview] | Treatment-related Esophagitis or Pneumonitis |
| NCT00288054 (5) [back to overview] | Overall Survival |
| NCT00288054 (5) [back to overview] | Response Rate |
| NCT00288080 (6) [back to overview] | Biochemical Control |
| NCT00288080 (6) [back to overview] | Disease-free Survival |
| NCT00288080 (6) [back to overview] | Distant Metastasis |
| NCT00288080 (6) [back to overview] | Local Control |
| NCT00288080 (6) [back to overview] | Overall Survival |
| NCT00288080 (6) [back to overview] | Incidence of Adverse Events |
| NCT00290693 (5) [back to overview] | Rate of Participants Achieving Complete Response or Partial Response to Therapy. |
| NCT00290693 (5) [back to overview] | Number of Study Participants Experiencing Toxicity After Receiving Protocol Therapy |
| NCT00290693 (5) [back to overview] | Overall Surival (OS) |
| NCT00290693 (5) [back to overview] | Progression-free Survival (PFS) |
| NCT00290693 (5) [back to overview] | Rate of Participants Achieving a 50% or More Reduction in CA 19-9 Levels |
| NCT00291577 (15) [back to overview] | Duration of Tumor Response Based on Investigator Assessment |
| NCT00291577 (15) [back to overview] | Number of Subjects With Clinical Benefit of Complete Response, Partial Response, or Stable Disease Based on Investigator Assessment |
| NCT00291577 (15) [back to overview] | Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Docetaxel PK Parameters |
| NCT00291577 (15) [back to overview] | Progression-Free Survival (PFS) Based on Investigator Assessment |
| NCT00291577 (15) [back to overview] | Area Under the Curve From Time 24 Hours to 48 Hours (AUC24_48) : Docetaxel PK Parameters |
| NCT00291577 (15) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero (0) to 24 Hours (AUC24): Docetaxel PK Parameters |
| NCT00291577 (15) [back to overview] | Area Under the Plasma Concentration-time Curve From Time Zero (0) to 48 Hours (AUC48): Docetaxel PK Parameters |
| NCT00291577 (15) [back to overview] | Maximum Observed Plasma Concentration (Cmax): Docetaxel PK Parameters |
| NCT00291577 (15) [back to overview] | Maximum Observed Plasma Concentration (Cmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters |
| NCT00291577 (15) [back to overview] | Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters |
| NCT00291577 (15) [back to overview] | Time to Reach Maximum Plasma Concentration (Tmax): Docetaxel PK Parameters |
| NCT00291577 (15) [back to overview] | Time to Reach Maximum Plasma Concentration (Tmax): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters |
| NCT00291577 (15) [back to overview] | Trough Plasma Concentration (Ctrough) at Time Zero (0): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters |
| NCT00291577 (15) [back to overview] | Area Under the Plasma Concentration-time Profile From Time Zero (0) to 24 Hours (AUC24): Sunitinib (SU011248), Sunitinib Metabolite (SU012662), and Total Drug PK Parameters |
| NCT00291577 (15) [back to overview] | Number of Subjects With Objective Response of Complete Response or Partial Response Based on Investigator Assessment |
| 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) |
| NCT00296816 (9) [back to overview] | CA-125 Response Rate |
| NCT00296816 (9) [back to overview] | Overall Survival Rate |
| NCT00296816 (9) [back to overview] | Tumor Response Rate Based on Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00296816 (9) [back to overview] | Twelve-month Recurrence-free Survival (RFS) Rate in Participants With Non Measurable Disease at Baseline |
| NCT00296816 (9) [back to overview] | Twenty Four-month Progression-free Survival (PFS) Rate in Participants |
| NCT00296816 (9) [back to overview] | Twelve-month Progression-free Survival (PFS) Rate in Participants |
| NCT00296816 (9) [back to overview] | Median Time to Recurrence-free Survival (RFS) in Participants With Non-measurable Disease at Baseline |
| NCT00296816 (9) [back to overview] | Median Time to Progression-free Survival (PFS) |
| NCT00296816 (9) [back to overview] | Median Overall Survival Time |
| NCT00301808 (4) [back to overview] | Overall Survival |
| NCT00301808 (4) [back to overview] | Safety Outcomes |
| NCT00301808 (4) [back to overview] | Progression-free Survival |
| NCT00301808 (4) [back to overview] | Probability of Overall Survival at One Year |
| 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] | Number of Participants With Complete Response (CR) or Partial Response (PR) [Tumor Response] |
| NCT00308750 (8) [back to overview] | Duration of CR or PR (Duration of Response) |
| NCT00308750 (8) [back to overview] | Change From Baseline in Total Functional Assessment of Cancer Therapy-Lung (FACT-L) Scale |
| NCT00308750 (8) [back to overview] | Number of Participants With Adverse Events (AEs) or Deaths |
| NCT00308750 (8) [back to overview] | Time to Disease Progression |
| NCT00308750 (8) [back to overview] | Overall Survival (OS) |
| NCT00309985 (6) [back to overview] | Proportion of Patients With PSA Complete Response (CR) at 12 Months |
| NCT00309985 (6) [back to overview] | Proportion of Patients With PSA Complete Response (CR) at 6 Months |
| NCT00309985 (6) [back to overview] | Overall Survival |
| NCT00309985 (6) [back to overview] | Time to Castration Resistant Prostate Cancer (Hormone Refractory Disease) |
| NCT00309985 (6) [back to overview] | Time to Clinical Progression |
| NCT00309985 (6) [back to overview] | QOL Change From Baseline to 3 Months |
| NCT00312208 (2) [back to overview] | Death From Any Cause (Overall Survival) |
| NCT00312208 (2) [back to overview] | Local, Regional or Metastatic Relapse, or Second Primary Cancer, or Death From Any Cause (Disease-Free Survival) |
| NCT00312377 (9) [back to overview] | Disease Control Rate (DCR) |
| NCT00312377 (9) [back to overview] | Duration of Response (DoR) |
| NCT00312377 (9) [back to overview] | Objective Response Rate (ORR) |
| NCT00312377 (9) [back to overview] | Overall Survival (OS) in the Overall Population |
| NCT00312377 (9) [back to overview] | Time to Deterioration of Disease-related Symptoms (TDS) by Functional Assessment of Cancer Therapy - Lung (FACT-L) Lung Cancer Subscale (LCS). |
| NCT00312377 (9) [back to overview] | Time to Deterioration of Disease-related Symptoms (TDS) by FACT-L Pulmonary Symptom Index (PSI) |
| NCT00312377 (9) [back to overview] | Progression-Free Survival (PFS) in the Overall Population |
| NCT00312377 (9) [back to overview] | Progression-Free Survival (PFS) in the Female Population |
| NCT00312377 (9) [back to overview] | Overall Survival (OS) in the Female Population |
| NCT00313781 (6) [back to overview] | Total Number of Circulation Tumor Cells (CTCs) |
| NCT00313781 (6) [back to overview] | Total Number of the Insulin Like Growth Factor Receptor Type 1 (IGF-1R) Positive CTCs |
| NCT00313781 (6) [back to overview] | Human Anti-human Antibody (HAHA) at Baseline (Day 1 of Cycle 1) |
| NCT00313781 (6) [back to overview] | Human Anti-human Antibody (HAHA) at the Last Follow-up Visit |
| NCT00313781 (6) [back to overview] | Percentage of Participants With Prostate Specific Antigen (PSA) Best Response |
| NCT00313781 (6) [back to overview] | Progression Free Survival (PFS) |
| NCT00320749 (3) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT00320749 (3) [back to overview] | Therapeutic Response |
| NCT00320749 (3) [back to overview] | Common Toxicities |
| NCT00321646 (2) [back to overview] | Endorectal MRI Response After Completion of 6 Cycles of Neoadjuvant Therapy |
| NCT00321646 (2) [back to overview] | PSA Response After Completing 6 Cycles of Neoadjuvant Chemotherapy. |
| NCT00321698 (6) [back to overview] | Prostate-specific Antigen Short-term Response Rate Measured as a Percentage Change in PSA |
| NCT00321698 (6) [back to overview] | Pathologic Response Rate at the Phase II Dose |
| NCT00321698 (6) [back to overview] | Surgical Margin Status at Time of Prostatectomy (Count of Subjects With Negative Surgical Margins) |
| NCT00321698 (6) [back to overview] | Efficacy Assessed Using Health-Related Quality of Life by Expanded Prostate Cancer Index Composite and Urinary Symptom Scores by American Urological Association's Measures |
| NCT00321698 (6) [back to overview] | Clinical Progression-free Rate as Determined by <0.1ng PSA Results |
| NCT00321698 (6) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT00324805 (2) [back to overview] | Overall Survival |
| NCT00324805 (2) [back to overview] | Disease-free Survival |
| NCT00327340 (4) [back to overview] | Safety and Tolerability of Custirsen (OGX-011) in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second-line Chemotherapy. |
| NCT00327340 (4) [back to overview] | Relationship Between Changes in Serum Clusterin Levels and Change in Serum PSA Levels When OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone is Administered as Second Line Chemotherapy. |
| NCT00327340 (4) [back to overview] | Feasibility of Treatment With OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second Line Chemotherapy Based on Time to Pain Progression |
| NCT00327340 (4) [back to overview] | Feasibility of Treatment With Custirsen (OGX-011) in Combination With Second-line Chemotherapy Based on Prostate Specific Antigen (PSA) Response |
| NCT00331682 (3) [back to overview] | Objective Response Rate as Measured by RECIST Criteria |
| NCT00331682 (3) [back to overview] | Overall Survival |
| NCT00331682 (3) [back to overview] | Time to Progression |
| NCT00333775 (5) [back to overview] | Progression-free Survival |
| NCT00333775 (5) [back to overview] | Time to Treatment Failure |
| NCT00333775 (5) [back to overview] | Percentage of Participants With a Complete Response or a Partial Response |
| NCT00333775 (5) [back to overview] | Overall Survival |
| NCT00333775 (5) [back to overview] | Duration of Response |
| NCT00334815 (4) [back to overview] | Overall Survival |
| NCT00334815 (4) [back to overview] | Progression-free Survival |
| NCT00334815 (4) [back to overview] | Response Rate (Confirmed or Unconfirmed Partial Response) |
| NCT00334815 (4) [back to overview] | Adverse Events |
| NCT00343512 (3) [back to overview] | Tumor Response as Measured by Ultrasound |
| NCT00343512 (3) [back to overview] | Safety Profile Based on Number of Patients With Each Worst-grade Toxicity |
| NCT00343512 (3) [back to overview] | Number Participants to Achieve Pathologic Complete Response |
| NCT00348816 (2) [back to overview] | Rate of Prostate-Specific Antigen (PSA) Decline Reported as the Number of Subjects Reaching a PSA Nadir of Zero Following the Intervention. |
| NCT00348816 (2) [back to overview] | Progression-free Survival Based on PSA Progression |
| NCT00354601 (1) [back to overview] | Number of Participants With Grade 3 or Higher Toxicity |
| NCT00356122 (5) [back to overview] | Progression-free Survival (PFS) |
| NCT00356122 (5) [back to overview] | Time-to-treatment Failure (TTF) |
| NCT00356122 (5) [back to overview] | Number of Participants With Treatment-related Toxicities |
| NCT00356122 (5) [back to overview] | Objective Response Rate |
| NCT00356122 (5) [back to overview] | Overall Survival (OS) |
| NCT00362882 (4) [back to overview] | Disease Control Rate |
| NCT00362882 (4) [back to overview] | Progression-free Survival @ 6 Months |
| NCT00362882 (4) [back to overview] | Overall Response Rate |
| NCT00362882 (4) [back to overview] | Overall Survival |
| NCT00364611 (7) [back to overview] | Confirmed Overall Response (OR) Based on RECIST Criteria |
| NCT00364611 (7) [back to overview] | Overall Survival (OS) Time |
| NCT00364611 (7) [back to overview] | Time to Progression-free Survival (PFS) |
| NCT00364611 (7) [back to overview] | Number of Participants With Adverse Events (AE) |
| NCT00364611 (7) [back to overview] | Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria |
| NCT00364611 (7) [back to overview] | Progression-free Survival (PFS) Rate: Percentage of Participants With PFS |
| NCT00364611 (7) [back to overview] | Duration of Response (DR) |
| NCT00365365 (3) [back to overview] | Cardiac Safety - Number of Participants With Grade 3-4 Clinical Congestive Heart Failure (CHF) |
| NCT00365365 (3) [back to overview] | Safety - Number of Participants With Adverse Events (AE) |
| NCT00365365 (3) [back to overview] | Disease-free Survival (DFS) Rate |
| NCT00365417 (8) [back to overview] | Reported Adverse Events |
| NCT00365417 (8) [back to overview] | Number of Patients With at Least One Surgical Complications (Wound Dehiscence, Infection, Seroma, or Hematoma). |
| NCT00365417 (8) [back to overview] | Overall Survival |
| NCT00365417 (8) [back to overview] | Progression-free Survival |
| NCT00365417 (8) [back to overview] | Clinical Response Rate (cRR) of the Sequential Regimen |
| NCT00365417 (8) [back to overview] | Cardiac Events |
| NCT00365417 (8) [back to overview] | pCR in the Breast and Nodes |
| NCT00365417 (8) [back to overview] | Pathologic Complete Response (pCR) in the Breast |
| NCT00372424 (6) [back to overview] | Duration of Response (DR) |
| NCT00372424 (6) [back to overview] | Percentage of Participants With Objective Response (OR) |
| NCT00372424 (6) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Docetaxel |
| NCT00372424 (6) [back to overview] | Plasma Trough Concentrations (Ctrough) of SU011248 (Sunitinib), SU012662 (Sunitinib Metabolite) and Total Drug (SU011248+SU012662) |
| NCT00372424 (6) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs) |
| NCT00372424 (6) [back to overview] | Progression-free Survival (PFS) |
| NCT00375999 (1) [back to overview] | Overall Survival |
| NCT00378573 (1) [back to overview] | Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00382720 (3) [back to overview] | Best Overall Response Rate (ORR) |
| NCT00382720 (3) [back to overview] | Overall Survival (OS) |
| NCT00382720 (3) [back to overview] | Time to Progression |
| NCT00390416 (3) [back to overview] | Patients With Measurable Disease the Confirmed Response Rate |
| NCT00390416 (3) [back to overview] | 1-year Survival |
| NCT00390416 (3) [back to overview] | 6 Month Progression Free Survival |
| NCT00390429 (7) [back to overview] | Comparison of Toxicity of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004]) |
| NCT00390429 (7) [back to overview] | Safety and Toxicity of Erlotinib Hydrochloride and Docetaxel as Measured by NCI CTC v3.0 on Day 8 of Course 1 and on Day 1 of Every Subsequent Course (Phase I [Completed as of 12/01/2004]) |
| NCT00390429 (7) [back to overview] | Response Rate (Phase II) |
| NCT00390429 (7) [back to overview] | Progression-free Survival (Phase II) |
| NCT00390429 (7) [back to overview] | Overall Survival (Phase II) |
| NCT00390429 (7) [back to overview] | Maximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004]) |
| NCT00390429 (7) [back to overview] | Frequency and Severity of Toxicities (Phase II) |
| NCT00391092 (7) [back to overview] | Overall Survival (OS) |
| NCT00391092 (7) [back to overview] | Functional Assessment of Cancer Therapy - Generic (FACT-G) and Functional Assessment of Cancer Therapy - Breast (FACT-B) Subscale Scores |
| NCT00391092 (7) [back to overview] | Change From Baseline for FACT-G and FACT-B |
| NCT00391092 (7) [back to overview] | Time to Treatment Failure (TTF) |
| NCT00391092 (7) [back to overview] | Progression Free Survival (PFS) |
| NCT00391092 (7) [back to overview] | Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR) in Participants With Measurable Disease at Baseline |
| NCT00391092 (7) [back to overview] | Duration of Response (DR) |
| NCT00391274 (5) [back to overview] | Number of Patients With Disease Progression |
| NCT00391274 (5) [back to overview] | Overall Tumor Response |
| NCT00391274 (5) [back to overview] | Overall Survival |
| NCT00391274 (5) [back to overview] | Progression-Free Survival (PFS) |
| NCT00391274 (5) [back to overview] | Pharmacology Toxicity |
| NCT00391586 (1) [back to overview] | Toxicity Profile |
| NCT00393939 (4) [back to overview] | Duration of Response (DR) |
| NCT00393939 (4) [back to overview] | Percentage of Participants With Objective Response |
| NCT00393939 (4) [back to overview] | Progression-Free Survival (PFS) |
| NCT00393939 (4) [back to overview] | Overall Survival (OS) |
| NCT00394433 (4) [back to overview] | Best Response |
| NCT00394433 (4) [back to overview] | Progression-Free Survival |
| NCT00394433 (4) [back to overview] | Overall Survival |
| NCT00394433 (4) [back to overview] | 10-month Progression-Free Survival Rate |
| NCT00400205 (2) [back to overview] | Number of Patients Who Had Response by RECIST Criteria (Response Evaluation Criteria in Solid Tumors) |
| NCT00400205 (2) [back to overview] | Tumor Change by Baseline Acetylated Tubulin Expression Score |
| NCT00404066 (2) [back to overview] | Disease-free Survival (DFS) |
| NCT00404066 (2) [back to overview] | Percentage of Participants With Pathologic Complete Response (pCR) |
| NCT00406276 (2) [back to overview] | Number of Subjects Showing Partial Response and Stable Disease With the Combination of RAD001 and Docetaxel. |
| NCT00406276 (2) [back to overview] | Time to Progression:Time Period (in Months) From Study Entry Until Disease Progression, Death, or Last Date of Contact. |
| NCT00408408 (9) [back to overview] | Toxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone |
| NCT00408408 (9) [back to overview] | pCR in the Breast and Nodes |
| NCT00408408 (9) [back to overview] | Clinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens |
| NCT00408408 (9) [back to overview] | Clinical Overall Response (cOR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at the Completion of the Docetaxel-based Portion of Chemotherapy |
| NCT00408408 (9) [back to overview] | Clinical Complete Response (cCR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at Completion of Therapy |
| NCT00408408 (9) [back to overview] | Clinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens |
| NCT00408408 (9) [back to overview] | Pathologic Complete Response (pCR) of the Primary Tumor in the Breast |
| NCT00408408 (9) [back to overview] | Surgical Complication |
| NCT00408408 (9) [back to overview] | Disease-free Survival (DFS) |
| NCT00414271 (4) [back to overview] | Number of Participants With Pathological Response |
| NCT00414271 (4) [back to overview] | Feasibility and Safety of Pre-operative Chemotherapy in Locally Advanced Gastric Cancer as Assessed by Number of Participants Who Experienced Adverse Events Grade 3 or Higher as Defined by CTCAE. |
| NCT00414271 (4) [back to overview] | Progression-free Survival as Measured by Number of Participants Without Disease Progression. |
| NCT00414271 (4) [back to overview] | Overall Survival |
| NCT00424840 (1) [back to overview] | Number of Subjects Who Require Dose Delay/Reduction in Dose of Bortezomibin the First Cycle |
| NCT00425750 (3) [back to overview] | Patient Response to Treatment |
| NCT00425750 (3) [back to overview] | Progression-free Survival |
| NCT00425750 (3) [back to overview] | Overall Survival |
| NCT00426127 (2) [back to overview] | Tumor Response Measured by CT Scans After Each Set of 3 Cycles of Chemotherapy |
| NCT00426127 (2) [back to overview] | Number of Blood Draws With Incidence of Elevated D-Dimer Measured by Drawing D-Dimer Levels Every Cycle |
| NCT00428922 (3) [back to overview] | Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen. |
| NCT00428922 (3) [back to overview] | Overall Clinical Benefit Rate (CR+PR+SD) |
| NCT00428922 (3) [back to overview] | Changes in CTCs as Predictors of PFS and Clinical Benefit |
| NCT00430183 (2) [back to overview] | 5-year bPFS Rate |
| NCT00430183 (2) [back to overview] | Proportion of Biochemical Progression-Free Survival (bPFS Proportion) at 3 Years |
| NCT00432172 (1) [back to overview] | Clinical Response Rate |
| NCT00436501 (7) [back to overview] | Overall Objective Response Rate According to RECIST (Phase II) |
| NCT00436501 (7) [back to overview] | Overall Median Duration of Response (Phase II) |
| NCT00436501 (7) [back to overview] | Number of Participants With Treatment-related Adverse Effects as Assessed by NCI CTCAE v3.0 (Phase II) |
| NCT00436501 (7) [back to overview] | Median Progression-Free Survival (PFS) (Phase II) |
| NCT00436501 (7) [back to overview] | Median Overall Survival (OS) (Phase II) |
| NCT00436501 (7) [back to overview] | Maximum Tolerated Dose of VEGF Trap (Phase I) |
| NCT00436501 (7) [back to overview] | Number of Participants With Clinical Response (Partial Response or Complete Response) According to the Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00439270 (16) [back to overview] | Baseline Scores and Changes in Pain Intensity From Baseline on the Brief Pain Inventory Short Form (BPI-sf) Scores Through Cycle 6 |
| NCT00439270 (16) [back to overview] | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Drug-related SAEs, Drug-related Adverse Events (AEs), Drug-related AEs Leading to Discontinuation, and Drug-related Grade 3 or 4 AEs in the Overall Population |
| NCT00439270 (16) [back to overview] | Number of Participants With Death as Outcome, Drug-related Serious Adverse Events (SAEs), Drug-related Adverse Events (AEs), Drug-related AEs Leading to Discontinuation, and Drug-related Grade 3 or 4 AEs in the Phase 2 Cohort |
| NCT00439270 (16) [back to overview] | Number of Participants Meeting the Criteria for On-study Abnormal Results Grade 3-4 of Clinical Laboratory Tests |
| NCT00439270 (16) [back to overview] | Number of Participants by Best On-study Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00439270 (16) [back to overview] | Number of Participants by Best On-study Bone Scan Assessment From Baseline |
| NCT00439270 (16) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Dasatinib and of Docetaxel |
| NCT00439270 (16) [back to overview] | Area Under the Concentration-time Curve (AUC) From 0 to 10 Hours Postdose (AUC [0-10])and AUC in 1 Dosing Interval, From Time 0 to 24 Hours (AUC[Tau])of Dasatinib Coadministered With Docetaxel |
| NCT00439270 (16) [back to overview] | Recommended Phase 2 Dose of Dasatinib Administered With Docetaxel, 75 mg/m^2 |
| NCT00439270 (16) [back to overview] | Percentage of Participants With Improvement on Bone Scan |
| NCT00439270 (16) [back to overview] | Percentage of Participants With an Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00439270 (16) [back to overview] | Percentage of Participants With a Prostate Specific Antigen (PSA) Response |
| NCT00439270 (16) [back to overview] | Number of Months of Progression-free Survival (PFS) |
| NCT00439270 (16) [back to overview] | Maximum Tolerated Dose (MTD) of Dasatinib Administered With Docetaxel |
| NCT00439270 (16) [back to overview] | Duration of Prostate Specific Antigen (PSA) Response |
| NCT00439270 (16) [back to overview] | Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity (AUC[Inf]) of Docetaxel |
| NCT00446030 (1) [back to overview] | Percent of Participants With Grade 3/4 Clinical Congestive Heart Failure (CHF) |
| NCT00446290 (1) [back to overview] | Number of Participants With DLTs |
| NCT00448760 (4) [back to overview] | Median Progression-free Survival (PFS) |
| NCT00448760 (4) [back to overview] | Overall Survival |
| NCT00448760 (4) [back to overview] | Pathologic Complete Response |
| NCT00448760 (4) [back to overview] | Clinical Response |
| NCT00454636 (6) [back to overview] | Progression-Free Survival (PFS) |
| NCT00454636 (6) [back to overview] | Overall Survival (OS) |
| NCT00454636 (6) [back to overview] | Overall Response Rate (ORR) |
| NCT00454636 (6) [back to overview] | Duration of Response |
| NCT00454636 (6) [back to overview] | Time to Response |
| NCT00454636 (6) [back to overview] | Percentage of Participants With Grade 3 Hand-Foot Syndrome (HFS) |
| 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 Pemetrexed |
| NCT00454649 (34) [back to overview] | Plasma Clearance (CL) for Pemetrexed |
| NCT00454649 (34) [back to overview] | Apparent Oral Clearance (CL/F) for Axitinib (AG-013736) |
| NCT00454649 (34) [back to overview] | Apparent Oral Clearance (CL/F) for Capecitabine |
| 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] | 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 Gemcitabine |
| 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 Pemetrexed |
| 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] | 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 8 Hours [AUC (0-8)] for Cisplatin |
| NCT00454649 (34) [back to overview] | Maximum Observed Plasma Concentration (Cmax) for Axitinib (AG-013736) |
| NCT00454649 (34) [back to overview] | Maximum Observed Plasma Concentration (Cmax) for Capecitabine |
| 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] | 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] | Plasma Clearance (CL) for Gemcitabine |
| NCT00454649 (34) [back to overview] | Plasma Clearance (CL) for Paclitaxel |
| 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 Capecitabine |
| 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 Cisplatin |
| 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 Gemcitabine |
| NCT00454779 (12) [back to overview] | Overall Response Rate (ORR) During the First-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Duration of Response (DOR) During the First-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Overall Response Rate (ORR) During the Second-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Time to Response (TTR) During the Second-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Time to Response (TTR) During the First-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Rate of Disease Control (RDC) During the Second-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Rate of Disease Control (RDC) During the First-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Progression Free Survival (PFS) During the Second-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Overall Survival (OS) for the Second-line Treatment |
| NCT00454779 (12) [back to overview] | Progression Free Survival (PFS) During the First-line Treatment Phase |
| NCT00454779 (12) [back to overview] | Overall Survival (OS) for the First-line Treatment |
| NCT00454779 (12) [back to overview] | Duration of Response (DOR) During the Second-line Treatment Phase |
| NCT00459043 (3) [back to overview] | Partial Response Rate in Both Groups of Patients. |
| NCT00459043 (3) [back to overview] | Overall Survival |
| NCT00459043 (3) [back to overview] | Progression Free Survival |
| NCT00459186 (2) [back to overview] | Response Based on PET Scan |
| NCT00459186 (2) [back to overview] | Number of Patients Free of Dose Limiting Toxicity |
| NCT00464646 (8) [back to overview] | Percentage of Participants With Surgical Complications (From Mastectomy, Lumpectomy, and Axillary Staging Procedures) (Cohort A) |
| NCT00464646 (8) [back to overview] | Number of Patients With Pathological Complete Response (pCR) in the Breast and Nodes for Patients With HER2-positive LABC Following Neoadjuvant Treatment (Cohort A) |
| NCT00464646 (8) [back to overview] | Number of Participants With no Histologic Evidence of Invasive Tumor Cells in the Surgical Breast Specimen. |
| NCT00464646 (8) [back to overview] | Overall Survival |
| NCT00464646 (8) [back to overview] | Recurrence-free Survival |
| NCT00464646 (8) [back to overview] | Clinical Complete Response (cCR) |
| NCT00464646 (8) [back to overview] | Grade 3 and 4 Toxicities, Including Toxicities Associated With Radiation Therapy(RT) |
| NCT00464646 (8) [back to overview] | Number of Participants With Cardiac Events |
| NCT00466440 (12) [back to overview] | Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) |
| NCT00466440 (12) [back to overview] | Part 2: Duration of Response |
| NCT00466440 (12) [back to overview] | Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020) |
| NCT00466440 (12) [back to overview] | Percentage of Participants Exhibiting a Decline in Prostate-Specific Androgen (PSA) From Baseline ≥30% Within First 3 Months of Treatment |
| NCT00466440 (12) [back to overview] | Part 2: Overall Survival (OS) |
| NCT00466440 (12) [back to overview] | Part 2: Progression Free Survival (PFS) |
| NCT00466440 (12) [back to overview] | Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Docetaxel |
| NCT00466440 (12) [back to overview] | Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Docetaxel |
| NCT00466440 (12) [back to overview] | Part 2: Percentage of Participants With Objective Tumor Response (Response Rate) |
| NCT00466440 (12) [back to overview] | Prostate-Specific Androgen (PSA) Velocity at 3 Months |
| NCT00466440 (12) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT00466440 (12) [back to overview] | Prostate-Specific Androgen (PSA) Velocity at 2 Months |
| NCT00475670 (10) [back to overview] | Percentage of Participants With Clinical Benefit According to RECIST Guidelines |
| NCT00475670 (10) [back to overview] | Overall Survival |
| NCT00475670 (10) [back to overview] | Percentage of Participants With Treatment Failure |
| NCT00475670 (10) [back to overview] | Progression-Free Survival |
| NCT00475670 (10) [back to overview] | Progression-free Survival (PFS) - Percentage of Participants With Progressive Disease |
| NCT00475670 (10) [back to overview] | Time to Treatment Failure |
| NCT00475670 (10) [back to overview] | Duration of Response - Percentage of Participants With Progressive Disease or Death |
| NCT00475670 (10) [back to overview] | Duration of Response |
| NCT00475670 (10) [back to overview] | Overall Survival - Percentage of Participants Who Died |
| NCT00475670 (10) [back to overview] | Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Guidelines |
| NCT00479089 (2) [back to overview] | Median Progression Free Survival From Trial Enrollment for Overall Study |
| NCT00479089 (2) [back to overview] | Median Overall Survival |
| NCT00479856 (1) [back to overview] | Overall Tumor Response |
| NCT00480857 (5) [back to overview] | The Number of Patients That Experience Evidence of Local Recurrence |
| NCT00480857 (5) [back to overview] | The Percentage of Patients That Experience at Least 1 Grade 1, 2, 3 and 4 Toxicities |
| NCT00480857 (5) [back to overview] | Percentage of Patients Alive Without Progression at 4 Years |
| NCT00480857 (5) [back to overview] | The Number of Patients Alive |
| NCT00480857 (5) [back to overview] | Number of Patients That Achieve a Post-radiotherapy PSA Nadir of 0.1 ng/mL or Less |
| NCT00482274 (1) [back to overview] | Number of Participants With a Complete Response as Measured by Serum PSA Less Than 0.2 ng/ml |
| NCT00485485 (1) [back to overview] | Participant Response Rate |
| NCT00488982 (4) [back to overview] | Overall Survival |
| NCT00488982 (4) [back to overview] | Cumulative Duration of Time on and Off Docetaxel-based Therapy |
| NCT00488982 (4) [back to overview] | Time to Progression |
| NCT00488982 (4) [back to overview] | Number of Participants With PSA Response to Successive Series of Chemotherapy |
| NCT00490646 (8) [back to overview] | Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 |
| NCT00490646 (8) [back to overview] | Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1) |
| NCT00490646 (8) [back to overview] | Progression Free Survival (PFS) |
| NCT00490646 (8) [back to overview] | Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0 |
| NCT00490646 (8) [back to overview] | Duration of Response |
| NCT00490646 (8) [back to overview] | Time to Response |
| NCT00490646 (8) [back to overview] | Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0 |
| NCT00490646 (8) [back to overview] | Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
| NCT00493649 (4) [back to overview] | OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. |
| NCT00493649 (4) [back to overview] | Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. |
| NCT00493649 (4) [back to overview] | DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H. |
| NCT00493649 (4) [back to overview] | Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H. |
| NCT00493870 (7) [back to overview] | 3-year DFS Stratified by TOP2A Among TC Arm |
| NCT00493870 (7) [back to overview] | 3-year DFS-DCIS, OS and RFI Among Per-protocol Patients. |
| NCT00493870 (7) [back to overview] | 3-year DFS Stratified by TOP2A Among TAC Arm |
| NCT00493870 (7) [back to overview] | Number and Frequency of Participants by TOP2A Status by Study Treatment |
| NCT00493870 (7) [back to overview] | 3-year DFS-DCIS, OS and RFI Among Analyzed ITT Patients |
| NCT00493870 (7) [back to overview] | 3-year Invasive Disease-free Survival (IDFS) Among Per-protocol Patients |
| NCT00493870 (7) [back to overview] | 3-year Invasive Disease-free Survival (IDFS) Among Analyzed ITT Patients |
| NCT00494481 (1) [back to overview] | Number of Patients With a Disease Progression Event |
| NCT00498797 (2) [back to overview] | Number of Patients With an Objective Disease Progression Event |
| NCT00498797 (2) [back to overview] | Prostate Specific Antigen (PSA) Response |
| NCT00499109 (3) [back to overview] | Progression Free Survival (PFS) |
| NCT00499109 (3) [back to overview] | Response Rate (RR) |
| NCT00499109 (3) [back to overview] | Overall Survival (OS) |
| NCT00499122 (3) [back to overview] | Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy |
| NCT00499122 (3) [back to overview] | Definition of the Safety Profiles of Protocol Therapy |
| NCT00499122 (3) [back to overview] | Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders |
| NCT00500110 (1) [back to overview] | Number of Participants Achieving Pathological Complete Response |
| NCT00503984 (8) [back to overview] | Progression-Free Survival (PFS) |
| NCT00503984 (8) [back to overview] | Overall Survival (OS) |
| NCT00503984 (8) [back to overview] | Number of Participants Experiencing Adverse Events After Beginning Protocol Therapy. |
| NCT00503984 (8) [back to overview] | Duration of Response |
| NCT00503984 (8) [back to overview] | Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Azacitidine and Docetaxel) |
| NCT00503984 (8) [back to overview] | Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Prednisone) |
| NCT00503984 (8) [back to overview] | Number of Participants Achieving Prostate-specific Antigen (PSA) Response. |
| NCT00503984 (8) [back to overview] | Number of Participants Achieving Complete Response (CR) or Partial Response (CR) to Protocol Therapy. |
| NCT00504257 (5) [back to overview] | Median Progression Free Survival |
| NCT00504257 (5) [back to overview] | Overall Response Rate (RR) |
| NCT00504257 (5) [back to overview] | Occurrence of Grade 3 or 4 Toxicity |
| NCT00504257 (5) [back to overview] | Six Month Progression Free Survival (PFS) |
| NCT00504257 (5) [back to overview] | Overall Survival (OS) |
| NCT00509366 (3) [back to overview] | Median Time to Progressive Disease |
| NCT00509366 (3) [back to overview] | 1-year Progression Free Survival Rate in Chemo-naive Select Stage IIIB or Stage IV NSCLC Patients |
| NCT00509366 (3) [back to overview] | Mean Change From Baseline to Follow-up Cycle in Quality of Life - Functional Assessment of Cancer Therapy-Lung (FACT-L) |
| 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. |
| NCT00514917 (11) [back to overview] | Change From Baseline in Erectile Function Domain of International Index of Erectile Function (EF-IIEF) Total Score at EOT |
| NCT00514917 (11) [back to overview] | Median Progression-Free Survival (PFS) in Intent-to-treat (ITT) Population |
| NCT00514917 (11) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index (TOI) Score at EOT |
| NCT00514917 (11) [back to overview] | Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Index Score at EOT |
| NCT00514917 (11) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) |
| NCT00514917 (11) [back to overview] | Median Progression-Free Survival (PFS) in Testosterone Specific Evaluable Population |
| NCT00514917 (11) [back to overview] | Progression-Free Survival (PFS) Rate at Month 36 in Testosterone Specific Evaluable Population |
| NCT00514917 (11) [back to overview] | Cancer-Specific Survival: Number of Participants Who Died (Cancer-Specific) |
| NCT00514917 (11) [back to overview] | Progression-Free Survival (PFS) Rate at Month 36 in ITT Population |
| NCT00514917 (11) [back to overview] | Overall Survival (OS): Number of Participants Who Died (All Cause) |
| NCT00514917 (11) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at End of Treatment (EOT) |
| NCT00515411 (2) [back to overview] | 6 Month Progression Free Survival (PFS) |
| NCT00515411 (2) [back to overview] | Overall Survival |
| NCT00517829 (5) [back to overview] | Overall Survival |
| NCT00517829 (5) [back to overview] | Progression-free Survival |
| NCT00517829 (5) [back to overview] | Time to Response |
| NCT00517829 (5) [back to overview] | Duration of Response |
| NCT00517829 (5) [back to overview] | Objective Response Rate (ORR) |
| NCT00519285 (11) [back to overview] | Prostate Specific Antigen Response Rate |
| NCT00519285 (11) [back to overview] | Time to Skeletal Related Events |
| NCT00519285 (11) [back to overview] | Tumor Response Rate in Participants With Measurable Disease |
| NCT00519285 (11) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate Total Score as a Measure of Health Related Quality of Life |
| NCT00519285 (11) [back to overview] | Number of Participants With Adverse Events as a Measure of Safety |
| NCT00519285 (11) [back to overview] | Number of Participants With Positive Anti-aflibercept Antibody Levels as a Measure of Immunogenicity of Aflibercept |
| NCT00519285 (11) [back to overview] | Overall Survival Time |
| NCT00519285 (11) [back to overview] | Pain Progression-free Survival Time |
| NCT00519285 (11) [back to overview] | Pain Response Rate |
| NCT00519285 (11) [back to overview] | Progression Free Survival Time |
| NCT00519285 (11) [back to overview] | Prostate Specific Antigen Progression-free Survival Time |
| NCT00520676 (8) [back to overview] | Percentage of Participants With Tumor Response (Response Rate) |
| NCT00520676 (8) [back to overview] | Survival Without Grade 3 or 4 Toxicity |
| 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 Clinically Important Grade 3 or 4 Toxicity |
| NCT00520676 (8) [back to overview] | Progression-free Survival (PFS) |
| NCT00520676 (8) [back to overview] | Overall Survival (OS) |
| NCT00520676 (8) [back to overview] | Duration of Response |
| NCT00520845 (3) [back to overview] | Time to Progression |
| NCT00520845 (3) [back to overview] | Overall Response Rate |
| NCT00520845 (3) [back to overview] | Median Survival |
| NCT00526110 (3) [back to overview] | Median Overall Survival |
| NCT00526110 (3) [back to overview] | Progression Free Survival |
| NCT00526110 (3) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT00527124 (5) [back to overview] | Prostate-specific Antigen (PSA) Response in Accordance With the Prostate Specific Antigen Working Group |
| NCT00527124 (5) [back to overview] | Overall Response Rate Evaluated by the RECIST Criteria |
| NCT00527124 (5) [back to overview] | Time to Progression |
| NCT00527124 (5) [back to overview] | Overall Survival |
| NCT00527124 (5) [back to overview] | 6-month Progression-free Survival (PFS) Proportion |
| NCT00528866 (9) [back to overview] | Local-regional Progression (3 Year Rate) |
| NCT00528866 (9) [back to overview] | Distant Metastasis (3-year Rate) |
| NCT00528866 (9) [back to overview] | "Number of Patients With Acute Adverse Events (Based on CTCAE, v3.0)" |
| NCT00528866 (9) [back to overview] | "Time to Late Grade 3+ Adverse Events (Based on CTCAE, v3.0)" |
| NCT00528866 (9) [back to overview] | Time to Biochemical (PSA) Failure (3-year Rate) |
| NCT00528866 (9) [back to overview] | Prostate Cancer Death (3-year Rate) |
| NCT00528866 (9) [back to overview] | Overall Survival (3-year Rate) |
| NCT00528866 (9) [back to overview] | Number of Participants Free From Progression at 3 Years |
| NCT00528866 (9) [back to overview] | Non-prostate Cancer Death (3-year Rate) |
| NCT00532155 (5) [back to overview] | Health Related Quality of Life (HRQL) Assessed by the Average Symptom Burden Index (ASBI) |
| NCT00532155 (5) [back to overview] | Overall Survival (OS) |
| NCT00532155 (5) [back to overview] | Progression Free Survival (PFS) |
| NCT00532155 (5) [back to overview] | Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria |
| NCT00532155 (5) [back to overview] | Health Related Quality of Life (HRQL) Assessed by the Lung Cancer Symptom Scale (LCSS) |
| NCT00532441 (3) [back to overview] | 16 Weeks Progression-free Survival |
| NCT00532441 (3) [back to overview] | Response Rate |
| NCT00532441 (3) [back to overview] | Overall Survival |
| NCT00536107 (2) [back to overview] | Number of Patients With Adverse Event (AE) |
| NCT00536107 (2) [back to overview] | Number of Patients With Serious Adverse Events (SAEs) |
| NCT00537381 (7) [back to overview] | Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration |
| NCT00537381 (7) [back to overview] | Number of Participants With Best Overall Response (OR) |
| NCT00537381 (7) [back to overview] | Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration |
| NCT00537381 (7) [back to overview] | Number of Participants With Prostate Specific Antigen (PSA) Response |
| NCT00537381 (7) [back to overview] | Overall Survival |
| NCT00537381 (7) [back to overview] | Progression-Free Survival (PFS) |
| NCT00537381 (7) [back to overview] | Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration |
| NCT00541099 (4) [back to overview] | Response Rate |
| NCT00541099 (4) [back to overview] | Survival |
| NCT00541099 (4) [back to overview] | Overall Survival |
| NCT00541099 (4) [back to overview] | Toxicity According to NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 |
| NCT00543387 (2) [back to overview] | Number of Participants With Dose Limiting Toxicities (DLTs) |
| NCT00543387 (2) [back to overview] | Number of Participants Who Experienced an Adverse Event (AE) |
| NCT00544414 (2) [back to overview] | Progression-free Survival |
| NCT00544414 (2) [back to overview] | Overall Response |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS) |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Best Primary Tumor Response (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Disease Progression [PD]) During Neo-Adjuvant Treatment by X-Ray/Mammography |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination |
| NCT00545688 (16) [back to overview] | Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Pathological Complete Response (pCR) |
| NCT00545688 (16) [back to overview] | Time to Clinical Response During Neo-Adjuvant Treatment Period |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned |
| NCT00545688 (16) [back to overview] | Percentage of Participants Who Were Progression Free and Disease Free |
| NCT00545688 (16) [back to overview] | Progression Free and Disease Free Survival |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving pCR by Hormone Receptor Status |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving pCR by Lymph Node Status |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving pCR by Breast Cancer Type |
| NCT00545688 (16) [back to overview] | Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination |
| NCT00546364 (8) [back to overview] | Percentage of Nontriple-negative (NTN) Participants With Best Response to Treatment of Complete or Partial Per Cohort |
| NCT00546364 (8) [back to overview] | Percentage of Participants With Best Response to Treatment of Complete or Partial |
| NCT00546364 (8) [back to overview] | Median Number of Treatment Cycles |
| NCT00546364 (8) [back to overview] | Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade |
| NCT00546364 (8) [back to overview] | Number of Participants With Abnormalities in Serum Chemistry Laboratory Results |
| NCT00546364 (8) [back to overview] | Number of Participants With Best Tumor Response as Assessed With Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00546364 (8) [back to overview] | Number of Participants With Death, Adverse Events (AEs), Drug-related AEs, Serious AEs (SAEs), Drug-related SAEs, AEs Leading to Discontinuation (AEDs), Drug-related AEDs, and Drug-related Peripheral Neuropathy |
| NCT00546364 (8) [back to overview] | Percentage of Triple-negative (TN) Participants With Best Response to Treatment of Complete or Partial |
| NCT00551759 (1) [back to overview] | Proportion of Patients With Pathologic Complete Response |
| NCT00556322 (22) [back to overview] | Duration of Overall Survival in All Participants (Data Cutoff 07 September 2010) |
| NCT00556322 (22) [back to overview] | Percentage of Participants Who Died in Epidermal Growth Factor Receptor (EGFR) Positive and Negative Population |
| NCT00556322 (22) [back to overview] | Duration of OS in EGFR Positive and Negative Population |
| NCT00556322 (22) [back to overview] | Time to Symptomatic Progression Using FACT-L |
| NCT00556322 (22) [back to overview] | Time to Deterioration in the TOI |
| NCT00556322 (22) [back to overview] | Time to Deterioration in Quality of Life Using FACT-L |
| NCT00556322 (22) [back to overview] | Progression-Free Survival (PFS) in All Participants (Data Cutoff 07 September 2010) |
| NCT00556322 (22) [back to overview] | Probable Percentage of Participants With Symptomatic Progression at 6 Months as Assessed by FACT-L |
| NCT00556322 (22) [back to overview] | Probable Percentage of Participants With Deterioration in the TOI at 6 Months as Assessed by FACT-L |
| NCT00556322 (22) [back to overview] | PFS in EGFR Positive and Negative Population (Data Cutoff 07 September 2010) |
| NCT00556322 (22) [back to overview] | Probable Percentage of Participants Remaining Without Deterioration in Quality of Life at 6 Months as Assessed by FACT-L |
| NCT00556322 (22) [back to overview] | Probable Percentage of Participants Remaining Alive at 1 Year |
| NCT00556322 (22) [back to overview] | Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months |
| NCT00556322 (22) [back to overview] | Percentage of Participants With Symptomatic Progression Using FACT-L |
| NCT00556322 (22) [back to overview] | Percentage of Participants With Disease Progression or Death (All Participants; Data Cut Off 07 September 2010) |
| NCT00556322 (22) [back to overview] | Percentage of Participants With Deterioration in the Trial Outcome Index (TOI) |
| NCT00556322 (22) [back to overview] | Percentage of Participants With Deterioration in Quality of Life Determined Using Functional Assessment of Cancer Therapy - Lung (FACT-L) |
| NCT00556322 (22) [back to overview] | Percentage of Participants Who Died (All Participants; Data Cutoff: 07 September 2010) |
| NCT00556322 (22) [back to overview] | Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator Using RECIST |
| NCT00556322 (22) [back to overview] | Probable Percentage of Participants Remaining Alive at 1 Year in the EGFR Positive and Negative Population |
| NCT00556322 (22) [back to overview] | Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months in EGFR Positive and Negative Population |
| NCT00556322 (22) [back to overview] | Percentage of Participants With Disease Progression or Death in EGFR Positive and Negative Population (Data Cut Off 07 September 2010) |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Insulin-Like Growth Factor (IGF) Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by KISS1 Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by KISS1 Protein Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Phosphorylated AKT (pAKT) Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Proliferation of Ki67 |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With Objective Clinical Response |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Angiotension Protein Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With Breast-Conserving Surgery |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by ENOS Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With Pathological Complete Response (pCR) |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Angiotensin II Receptor Type I (AGTR) Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by HIF Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by Vascular Endothelial Growth Factor (VEGF) Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by RKISS1 Gene Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by VEGFR Protein Expression |
| NCT00559754 (21) [back to overview] | Percentage of Participants With pCR by VEGFR Gene Expression |
| NCT00564733 (1) [back to overview] | Overall Response Rate (Patients That Achieve a CR or PR) |
| NCT00565448 (4) [back to overview] | Overall Response (OR) |
| NCT00565448 (4) [back to overview] | Docetaxel Area Under the Plasma Concentration-time Curve (AUC) in the Docetaxel/Cisplatin/5-FU Group |
| NCT00565448 (4) [back to overview] | Number of Participants With Complete Response (CR) |
| NCT00565448 (4) [back to overview] | Overall Survival (OS) Rate |
| NCT00565851 (9) [back to overview] | Summary of Adverse Events (CTCAE Version 4.0) |
| NCT00565851 (9) [back to overview] | Progression Free Survival (Surgery Analysis) |
| NCT00565851 (9) [back to overview] | Progression-free Survival (Chemotherapy Analysis) |
| 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] | 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 |
| NCT00567190 (17) [back to overview] | Baseline LVEF Value and Change in LVEF From Baseline at Maximum Absolute Decrease Value During the Treatment Period |
| NCT00567190 (17) [back to overview] | Overall Number of Participants Who Experienced at Least One Adverse Event, Including Serious and Non-Serious Adverse Events, by Most Severe Intensity (According to NCI-CTCAE v3.0) During the Treatment Period |
| NCT00567190 (17) [back to overview] | Time to Symptom Progression |
| NCT00567190 (17) [back to overview] | Overall Survival |
| NCT00567190 (17) [back to overview] | Number of Participants by Categories for the Maximum Absolute Decrease From Baseline in LVEF Value During the Treatment Period |
| NCT00567190 (17) [back to overview] | Number of Participants Who Experienced at Least One Adverse Event During the Post-Treatment Follow-Up Period |
| NCT00567190 (17) [back to overview] | Number of Participants Who Experienced at Least One Adverse Event to Monitor (Excluding Cardiac-Related AEs) by Severity During the Treatment Period |
| NCT00567190 (17) [back to overview] | Cardiac-Related AEs to Monitor: Number of Participants Who Experienced at Least One Symptomatic Left Ventricular Dysfunction (LVD), Any LVD, or Serious AE Suggestive of Congestive Heart Failure by Severity During the Treatment Period |
| NCT00567190 (17) [back to overview] | Number of Participants With Laboratory Abnormalities in Blood Biochemistry Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period |
| NCT00567190 (17) [back to overview] | Number of Participants With Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period |
| NCT00567190 (17) [back to overview] | Objective Response Determined by an Independent Review Facility |
| NCT00567190 (17) [back to overview] | Overall Number of Adverse Events by Severity (NCI-CTCAE v3.0 All Grades and Grades 3 to 5) Per 100 Patient-Years of Exposure During the Treatment Period |
| NCT00567190 (17) [back to overview] | Overall Number of Participants Who Experienced at Least One Adverse Event Leading to Discontinuation of Any or All Study Medication |
| NCT00567190 (17) [back to overview] | Duration of Objective Response Determined by an Independent Review Facility |
| NCT00567190 (17) [back to overview] | Overall Number of Participants Who Experienced at Least One Adverse Event That Resulted in Interruption or Modification of Any Study Medication |
| NCT00567190 (17) [back to overview] | Progression-Free Survival (PFS) Determined by an Independent Review Facility |
| NCT00567190 (17) [back to overview] | Progression-Free Survival (PFS) Determined by the Investigator |
| NCT00569673 (2) [back to overview] | Objective Tumor Response |
| NCT00569673 (2) [back to overview] | Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 |
| NCT00576901 (3) [back to overview] | Percentage of Participants Undergoing Breast-Conserving Surgery |
| NCT00576901 (3) [back to overview] | Percentage of Participants Achieving Pathological Complete Response (pCR) |
| NCT00576901 (3) [back to overview] | Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR) |
| NCT00583622 (1) [back to overview] | Participant Response |
| NCT00587431 (2) [back to overview] | PSA of <_ 0.05 ng/ml After Radical Prostatectomy or Radiation Therapy and PSA <_ 2.0 ng/ml for Patients With Clinical Metastases Without Prior Definitive Therapy |
| NCT00587431 (2) [back to overview] | The Effects of Testosterone Administration on Docetaxel Pharmacokinetics. |
| 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 |
| NCT00589420 (3) [back to overview] | Prostate Specific Antigen (PSA) Response Rate |
| NCT00589420 (3) [back to overview] | 6-month Progression-free Survival (PFS) |
| NCT00589420 (3) [back to overview] | Objective Response Rate (ORR) |
| NCT00591149 (1) [back to overview] | Efficacy Measured by Response Rate in Participants |
| NCT00609336 (7) [back to overview] | Median Overall Survival of Patients With Adenocarcinoma of the Pancreas |
| NCT00609336 (7) [back to overview] | Percent of Patients Surviving at Annual Intervals |
| NCT00609336 (7) [back to overview] | Surgical Completion Rate and Complication Rate |
| NCT00609336 (7) [back to overview] | Frequency and Severity of Toxicities Associated With This Treatment Regimen as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 |
| NCT00609336 (7) [back to overview] | Percent of Patients Surviving at 5 Years |
| NCT00609336 (7) [back to overview] | Pathologic Response Rate (Complete, Near-complete, Partial) to Neoadjuvant Chemotherapy and Chemoradiotherapy |
| NCT00609336 (7) [back to overview] | Median Recurrence Free Survival Following Pancreaticoduodenectomy |
| NCT00617669 (8) [back to overview] | Health Related Quality of Life |
| NCT00617669 (8) [back to overview] | Incidence of Skeletal Related Events |
| NCT00617669 (8) [back to overview] | Overall Survival |
| NCT00617669 (8) [back to overview] | Pain Response |
| NCT00617669 (8) [back to overview] | Progression Free Survival |
| NCT00617669 (8) [back to overview] | PSA Response |
| NCT00617669 (8) [back to overview] | Time to Pain Progression |
| NCT00617669 (8) [back to overview] | Time to Prostate-specific Antigen (PSA) Progression |
| NCT00621049 (4) [back to overview] | Disease-free Survival |
| NCT00621049 (4) [back to overview] | Safety |
| NCT00621049 (4) [back to overview] | Overall Survival (OS) |
| NCT00621049 (4) [back to overview] | 2-year Survival |
| NCT00630032 (6) [back to overview] | Number of Disease-free Survival Events for Triple-negative Subgroup |
| NCT00630032 (6) [back to overview] | Number of Event-free Survival |
| NCT00630032 (6) [back to overview] | Overall Survival |
| NCT00630032 (6) [back to overview] | Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup |
| NCT00630032 (6) [back to overview] | Percentage of Participants With Disease-free Survival (DFS) |
| NCT00630032 (6) [back to overview] | Number of Distant Metastasis-free Survival Events for the Whole Population |
| NCT00636441 (6) [back to overview] | Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer |
| NCT00636441 (6) [back to overview] | Disease-free Survival |
| NCT00636441 (6) [back to overview] | Sites of Recurrence |
| NCT00636441 (6) [back to overview] | Clinical Response Using WHO Criteria |
| NCT00636441 (6) [back to overview] | To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt. |
| NCT00636441 (6) [back to overview] | Overall Survival |
| NCT00642018 (12) [back to overview] | Estimate Overall Survival |
| NCT00642018 (12) [back to overview] | Percentage of Participants With Complete Response or Partial Response (Overall Response Rate) |
| NCT00642018 (12) [back to overview] | Prostate Specific Antigen (PSA) Kinetics: Percentage of Participants With PSA Response (Response Rate) |
| NCT00642018 (12) [back to overview] | Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment |
| NCT00642018 (12) [back to overview] | Change From Baseline to Day 21 in Granulocyte Colony Stimulating Factor(G-CSF) (Assess Biomarker Responses) |
| NCT00642018 (12) [back to overview] | Number of Participants With Adverse Events (Safety) |
| NCT00642018 (12) [back to overview] | Functional Assessment of Cancer Therapy-General (FACT-G) Total Score at 3 Months (Evaluate Clinical Symptoms) |
| NCT00642018 (12) [back to overview] | Adverse Event Profile |
| NCT00642018 (12) [back to overview] | Progression-free Survival (PFS) in Participants With Hormone Refractory Prostate Cancer (HRPC) Administered LY2181308 Sodium Plus Docetaxel Compared to Docetaxel Alone |
| NCT00642018 (12) [back to overview] | Estimate Duration of Overall Response |
| NCT00642018 (12) [back to overview] | Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) Total Score at 3 Months (Participant Reported Outcomes) |
| NCT00642018 (12) [back to overview] | Pharmacokinetics of Docetaxel: Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-infinity) |
| NCT00645333 (2) [back to overview] | Dose Limiting Toxicity (DLT) |
| NCT00645333 (2) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT00658697 (5) [back to overview] | Proportion of Patients With PSA Responses at One Year After the Completion of ADT |
| NCT00658697 (5) [back to overview] | Time to PSA Progression (TTP) |
| NCT00658697 (5) [back to overview] | Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT) |
| NCT00658697 (5) [back to overview] | Toxicity |
| NCT00658697 (5) [back to overview] | Testosterone Recovery |
| NCT00659269 (4) [back to overview] | Neurotoxicity Assessment at Baseline |
| NCT00659269 (4) [back to overview] | Neurotoxicity Assessment at Cycle 4 |
| NCT00659269 (4) [back to overview] | Neurotoxicity Assessment at Cycle 2 |
| NCT00659269 (4) [back to overview] | Change in Neurotoxicity Assessment Between Cycle 4 and Baseline |
| NCT00660699 (8) [back to overview] | Disease Free Survival (DFS) - Median |
| NCT00660699 (8) [back to overview] | Toxicities Associated With Treatment (Grade 1-2) |
| NCT00660699 (8) [back to overview] | Overall Survival (OS) |
| NCT00660699 (8) [back to overview] | Overall Survival (OS) |
| NCT00660699 (8) [back to overview] | Toxicities Associated With Treatment (Grade 3-4) |
| NCT00660699 (8) [back to overview] | Incidence of Severe Toxicities |
| NCT00660699 (8) [back to overview] | Overall Survival (OS) - Median |
| NCT00660699 (8) [back to overview] | Incidence of Disease Recurrence |
| NCT00660816 (4) [back to overview] | Response Rate |
| NCT00660816 (4) [back to overview] | Progression-free Survival |
| NCT00660816 (4) [back to overview] | Overall Survival |
| NCT00660816 (4) [back to overview] | Disease Stabilization Rate (e.g., Complete Response, Partial Response, and Stable Disease) |
| NCT00661778 (4) [back to overview] | Progression-free Survival |
| NCT00661778 (4) [back to overview] | Percentage of Participants With an Objective Response |
| NCT00661778 (4) [back to overview] | 1-year Survival |
| NCT00661778 (4) [back to overview] | Overall Survival |
| 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 |
| NCT00665392 (7) [back to overview] | Complete Radiological Response (rCR) |
| NCT00665392 (7) [back to overview] | Pathologic Response |
| NCT00665392 (7) [back to overview] | The 2-year Estimated Overall Survival (OS) Rate |
| NCT00665392 (7) [back to overview] | The 2-year Estimated Progression-free Survival (PFS) |
| NCT00665392 (7) [back to overview] | Biomarkers Analysis - HPV Genotyping |
| NCT00665392 (7) [back to overview] | Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months |
| NCT00665392 (7) [back to overview] | Complete Clinical Response (cCR) |
| NCT00665457 (1) [back to overview] | Number of Participants With Grade 4 Adverse Events |
| NCT00667251 (10) [back to overview] | CNS Metastases at the Time of Progression (HER2+) |
| NCT00667251 (10) [back to overview] | Progression-free Survival |
| NCT00667251 (10) [back to overview] | Time to CNS Metastases at the Time of First Progression |
| NCT00667251 (10) [back to overview] | Clinical Benefit Response Rate (HER2/Neu+)) |
| NCT00667251 (10) [back to overview] | Clinical Benefit Response Rate (ITT) |
| NCT00667251 (10) [back to overview] | CNS Metastases at the Time of Progression (ITT) |
| NCT00667251 (10) [back to overview] | Overall Objective Response Rate (Complete or Partial) HER2/Neu+ |
| NCT00667251 (10) [back to overview] | Overall Objective Response Rate (Complete or Partial) ITT |
| NCT00667251 (10) [back to overview] | Overall Survival |
| NCT00667251 (10) [back to overview] | Quality of Life as Measured by the EORTC QLQ-C30 Global Score From Baseline to 12 Weeks |
| NCT00669162 (1) [back to overview] | Percentage of Patients Who Can Safely Tolerate and Complete Adjuvant Hormonal Therapy, Radiation Therapy and Docetaxel After a Radical Prostatectomy |
| NCT00673738 (3) [back to overview] | Overall Response Rate (ORR) |
| NCT00673738 (3) [back to overview] | Median Overall Survival (OS) |
| NCT00673738 (3) [back to overview] | Median Progression Free Survival (PFS) |
| NCT00675597 (1) [back to overview] | To Measure the Number of Cycles |
| NCT00679341 (8) [back to overview] | Clinical Benefit (CB) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00679341 (8) [back to overview] | Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00679341 (8) [back to overview] | Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00679341 (8) [back to overview] | Overall Survival |
| NCT00679341 (8) [back to overview] | Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST) |
| NCT00679341 (8) [back to overview] | Time to Symptom Progression |
| NCT00679341 (8) [back to overview] | Plasma Concentration of Free Emtansine |
| NCT00679341 (8) [back to overview] | Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine and Total Trastuzumab |
| NCT00687297 (3) [back to overview] | Progression-free Survival |
| NCT00687297 (3) [back to overview] | Progression-free Survival |
| NCT00687297 (3) [back to overview] | Objective Response Rate |
| NCT00687440 (1) [back to overview] | Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria |
| NCT00688740 (3) [back to overview] | Number of Participants With Second Primary Malignancies (Toxicity) |
| NCT00688740 (3) [back to overview] | Number of Participants With Disease-Free Survival Events |
| NCT00688740 (3) [back to overview] | Number of Participants With Overall Survival Events |
| NCT00703326 (9) [back to overview] | Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate) |
| NCT00703326 (9) [back to overview] | Overall Survival (OS) |
| NCT00703326 (9) [back to overview] | Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013 |
| NCT00703326 (9) [back to overview] | Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016 |
| NCT00703326 (9) [back to overview] | Duration of Response |
| NCT00703326 (9) [back to overview] | Number of Participants With Adverse Events |
| NCT00703326 (9) [back to overview] | Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy |
| NCT00703326 (9) [back to overview] | Time to Progression (TTP) |
| NCT00703326 (9) [back to overview] | Progression-Free Survival (PFS) |
| NCT00705874 (1) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT00711243 (5) [back to overview] | Toxicity Profile |
| NCT00711243 (5) [back to overview] | Response Rate in Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction (Phase II) |
| NCT00711243 (5) [back to overview] | Median Overall Survival (OS) |
| NCT00711243 (5) [back to overview] | Dose-limiting Toxicity of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil |
| NCT00711243 (5) [back to overview] | Maximum Tolerated Dose (MTD) of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil (Phase I) |
| NCT00713219 (1) [back to overview] | Overall Progression-Free Survival (PFS). |
| NCT00721513 (7) [back to overview] | Quality of Life - Functional Assessment of Cancer Therapy - General (FACT-G) |
| NCT00721513 (7) [back to overview] | Performance Status Scale for Head and Neck Cancer |
| NCT00721513 (7) [back to overview] | MD Anderson Dysphagia Inventory |
| NCT00721513 (7) [back to overview] | Progression-free Survival |
| NCT00721513 (7) [back to overview] | Overall Survival |
| NCT00721513 (7) [back to overview] | Number of Participants With Local-Regional Control |
| NCT00721513 (7) [back to overview] | Number of Participants With Distant Metastasis |
| NCT00734851 (5) [back to overview] | The Rate of Progression Free Survival (PFS) at 24 Months |
| NCT00734851 (5) [back to overview] | Proportion of Biochemical Progression (bPFS Proportion) at 2 and 3 Years. |
| NCT00734851 (5) [back to overview] | Rate of Local Recurrence at 2 and 3 Years |
| NCT00734851 (5) [back to overview] | Change in Quality of Life (QoL) After 3 Month |
| NCT00734851 (5) [back to overview] | Change in Quality of Life (QoL) After 1 Year |
| NCT00737438 (1) [back to overview] | Overall Response Will be Characterized by the Patient's FDG-PET Scan |
| NCT00744497 (15) [back to overview] | Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology |
| NCT00744497 (15) [back to overview] | Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes |
| NCT00744497 (15) [back to overview] | Percentage of Participants With a Reduction in Pain Intensity From Baseline |
| NCT00744497 (15) [back to overview] | Overall Survival: Time From Randomization to Date of Death |
| NCT00744497 (15) [back to overview] | Number of Participants With Abnormal Results in Urinalysis |
| NCT00744497 (15) [back to overview] | Number of Participants by Maximal On-study Fridericia-corrected QTc Interval |
| NCT00744497 (15) [back to overview] | Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest |
| NCT00744497 (15) [back to overview] | Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline |
| NCT00744497 (15) [back to overview] | Time to First Skeletal-related Event (SRE) |
| NCT00744497 (15) [back to overview] | Progression-free Survival (PFS) |
| NCT00744497 (15) [back to overview] | Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00744497 (15) [back to overview] | Time to Prostate Specific Antigen (PSA) Progression |
| NCT00744497 (15) [back to overview] | Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval |
| NCT00744497 (15) [back to overview] | Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study |
| NCT00744497 (15) [back to overview] | Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths |
| NCT00757172 (5) [back to overview] | Percentage of Participants With 3-year Overall Survival |
| NCT00757172 (5) [back to overview] | Percentage of Participants With 2-year Disease-free Survival |
| NCT00757172 (5) [back to overview] | Number of Participants With Near-complete Response Rate (≤ 10% Residual Cancer in Primary Tumor Viable) |
| NCT00757172 (5) [back to overview] | Number of Participants With Pathologic Complete Response Following Surgery |
| NCT00757172 (5) [back to overview] | Number of Participants With Frequent (>=15% Grade 3/4 Incidence) Adverse Events Regardless of Attribution |
| NCT00771953 (1) [back to overview] | Progression Free Survival |
| NCT00801801 (2) [back to overview] | Response Rate in Poor Performance Status Subjects |
| NCT00801801 (2) [back to overview] | 2-month Progression-free Survival Rate |
| NCT00805194 (14) [back to overview] | Duration of Confirmed Objective Tumour Response |
| NCT00805194 (14) [back to overview] | Duration of Disease Control |
| NCT00805194 (14) [back to overview] | Incidence and Intensity of Adverse Events |
| NCT00805194 (14) [back to overview] | Objective Tumour Response |
| NCT00805194 (14) [back to overview] | Clinical Improvement |
| NCT00805194 (14) [back to overview] | Change From Baseline in Tumour Size |
| NCT00805194 (14) [back to overview] | Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review |
| NCT00805194 (14) [back to overview] | Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator |
| NCT00805194 (14) [back to overview] | Progression Free Survival (PFS) as Assessed by Central Independent Review |
| NCT00805194 (14) [back to overview] | Overall Survival (Key Secondary Endpoint) |
| NCT00805194 (14) [back to overview] | Disease Control |
| NCT00805194 (14) [back to overview] | Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide |
| NCT00805194 (14) [back to overview] | Time to Confirmed Objective Tumour Response |
| NCT00805194 (14) [back to overview] | Quality of Life (QoL) |
| NCT00820872 (1) [back to overview] | Proportion of Patients Experiencing Grade 3 or 4 Diarrhea as Measured by NCI CTCAE v3.0 |
| NCT00841828 (2) [back to overview] | Complete Pathological Response (pCR) Rate in Breast and Axilla According to the Miller&Payne Criteria (G5-A and G5-D). |
| NCT00841828 (2) [back to overview] | Overall Clinical Response Rate (ORR) |
| 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] | 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 Experienced a Dose Limiting Toxicity (DLT) During Cycle 1 |
| 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] | Time to Maximum Plasma Concentration of MK-2206 (Tmax) |
| NCT00848718 (12) [back to overview] | Area Under the MK-2206 Concentration Versus Time Curve From Time Zero to 48 Hours Postdose (AUC 0-48h) |
| 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 |
| NCT00861471 (5) [back to overview] | Time to PSA Progression |
| NCT00861471 (5) [back to overview] | Percentage of Participants With Greater or Equal to 80% PSA Reduction From Baseline Without Clinical or Radiologic Evidence of Progression |
| NCT00861471 (5) [back to overview] | Percentage of Participants With Measurable Disease Response |
| NCT00861471 (5) [back to overview] | Median Overall Survival Time |
| NCT00861471 (5) [back to overview] | Percentage of Participants With Prostate Specific Antigen (PSA) Response |
| NCT00862134 (3) [back to overview] | Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients |
| NCT00862134 (3) [back to overview] | Safety and Tolerability: Serious Adverse Events |
| NCT00862134 (3) [back to overview] | Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone |
| NCT00872989 (6) [back to overview] | Progression Free Survival (PFS) |
| NCT00872989 (6) [back to overview] | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT00872989 (6) [back to overview] | Overall Survival |
| NCT00872989 (6) [back to overview] | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel |
| NCT00872989 (6) [back to overview] | Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease |
| NCT00872989 (6) [back to overview] | Time to Treatment Failure |
| NCT00876460 (13) [back to overview] | Clinical Relevant Abnormalities in Laboratory Parameters |
| NCT00876460 (13) [back to overview] | AUC0-inf of Docetaxel in Course 2 |
| NCT00876460 (13) [back to overview] | Cmax of Docetaxel in Course 1 |
| NCT00876460 (13) [back to overview] | AUC0-inf of Nintedanib in Course 1 |
| NCT00876460 (13) [back to overview] | Objective Tumor Response |
| NCT00876460 (13) [back to overview] | Disease Control |
| NCT00876460 (13) [back to overview] | Time to Treatment Failure (TTF) |
| NCT00876460 (13) [back to overview] | Progression-Free Survival (PFS) |
| NCT00876460 (13) [back to overview] | Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel |
| NCT00876460 (13) [back to overview] | Cmax of Nintedanib in Course 1 |
| NCT00876460 (13) [back to overview] | Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses |
| NCT00876460 (13) [back to overview] | Cmax of Docetaxel in Course 2 |
| NCT00876460 (13) [back to overview] | AUC0-inf of Docetaxel in Course 1 |
| NCT00880334 (5) [back to overview] | Median Progression-Free Survival (PFS) |
| NCT00880334 (5) [back to overview] | Grade 3-5 Toxicity Rate |
| NCT00880334 (5) [back to overview] | Disease Control Rate |
| NCT00880334 (5) [back to overview] | Objective Response Rate |
| NCT00880334 (5) [back to overview] | Median Overall Survival |
| NCT00883675 (1) [back to overview] | Febrile Neutropenia |
| NCT00887809 (1) [back to overview] | Overall Objective Response |
| NCT00890825 (4) [back to overview] | Alive and Progression-Free at 6 Months |
| NCT00890825 (4) [back to overview] | Change From Baseline in Tumour Size at 6 Week. |
| NCT00890825 (4) [back to overview] | Change From Baseline in Tumour Size at Week 12 |
| NCT00890825 (4) [back to overview] | Duration of Response |
| NCT00896181 (5) [back to overview] | Overall Survival (OS) |
| NCT00896181 (5) [back to overview] | Number of Participants With Adverse Events Resulting in Treatment Discontinuation |
| NCT00896181 (5) [back to overview] | Median Progression-free Survival (PFS) |
| NCT00896181 (5) [back to overview] | Number of Participants With Progression-free Survival (PFS) at 2 Years After Chemo-radiotherapy |
| NCT00896181 (5) [back to overview] | Number of Participants With Treatment Response |
| NCT00911820 (5) [back to overview] | Best Response |
| NCT00911820 (5) [back to overview] | 7-month Progression-Free Survival |
| NCT00911820 (5) [back to overview] | Overall Response (OR) Rate |
| NCT00911820 (5) [back to overview] | Overall Survival |
| NCT00911820 (5) [back to overview] | Progression-Free Survival |
| 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 |
| 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] | 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] | Number of Participants With Abnormal Changes in PR Interval |
| 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] | 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] | Minimum Observed Serum Trough Concentration (Cmin) of Trastuzumab |
| NCT00927589 (19) [back to overview] | Maximum Observed Serum Concentration (Cmax) of Trastuzumab |
| NCT00932893 (15) [back to overview] | Overall Survival (OS) |
| NCT00932893 (15) [back to overview] | Percentage of Participants With Disease Control at Week 12 |
| NCT00932893 (15) [back to overview] | Percentage of Participants With Disease Control at Week 6 |
| NCT00932893 (15) [back to overview] | Percentage of Participants With Objective Response (OR) |
| NCT00932893 (15) [back to overview] | Progression-Free Survival (PFS) |
| NCT00932893 (15) [back to overview] | Time to Tumor Response (TTR) |
| NCT00932893 (15) [back to overview] | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) |
| NCT00932893 (15) [back to overview] | Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough |
| NCT00932893 (15) [back to overview] | Duration of Response (DR) |
| NCT00932893 (15) [back to overview] | European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13) |
| NCT00932893 (15) [back to overview] | European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS) |
| NCT00932893 (15) [back to overview] | Overall Survival Probability at Months 6 and 12 |
| NCT00932893 (15) [back to overview] | Plasma Concentration of Crizotinib |
| NCT00932893 (15) [back to overview] | Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins |
| NCT00932893 (15) [back to overview] | Number of Participants With Categorical Maximum QTcF for Crizotinib |
| NCT00934856 (30) [back to overview] | t1/2 of Total Serum Trastuzumab |
| NCT00934856 (30) [back to overview] | CL of Total Serum Trastuzumab |
| NCT00934856 (30) [back to overview] | t1/2 of Plasma Docetaxel |
| NCT00934856 (30) [back to overview] | Clearance (CL) of Serum Trastuzumab Emtansine |
| NCT00934856 (30) [back to overview] | Cmax of Plasma Docetaxel |
| NCT00934856 (30) [back to overview] | Cmax of Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1) |
| NCT00934856 (30) [back to overview] | t1/2 of Plasma DM1 |
| NCT00934856 (30) [back to overview] | Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) - MBC and LABC Population |
| NCT00934856 (30) [back to overview] | Number of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab - MBC and LABC Population |
| NCT00934856 (30) [back to overview] | Cmax of Total Serum Trastuzumab |
| NCT00934856 (30) [back to overview] | Volume of Distribution at Steady State (Vss) of Serum Trastuzumab Emtansine |
| NCT00934856 (30) [back to overview] | AUCinf of Plasma DM1 |
| NCT00934856 (30) [back to overview] | AUCinf of Plasma Docetaxel |
| NCT00934856 (30) [back to overview] | AUCinf of Total Serum Trastuzumab |
| NCT00934856 (30) [back to overview] | CL of Plasma Docetaxel |
| NCT00934856 (30) [back to overview] | Vss of Total Serum Trastuzumab |
| NCT00934856 (30) [back to overview] | Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) - MBC Population |
| NCT00934856 (30) [back to overview] | Time to Treatment Failure (TTF) - MBC Population |
| NCT00934856 (30) [back to overview] | PFS - MBC Population |
| NCT00934856 (30) [back to overview] | Duration of Response - MBC Population |
| NCT00934856 (30) [back to overview] | Percentage of Participants With a BOR of CR or PR - LABC Population |
| NCT00934856 (30) [back to overview] | Percentage of Participants With CR or PR or Stable Disease (SD) for at Least 6 Months [Clinical Benefit Rate (CBR)] - MBC Population |
| NCT00934856 (30) [back to overview] | Percentage of Participants With Pathological CR (pCR) - LABC Population |
| NCT00934856 (30) [back to overview] | Percentage of Participants With Progression-Free Survival (PFS) Event - MBC Population |
| NCT00934856 (30) [back to overview] | Number of Participants With Dose Limiting Toxicity (DLT) - MBC and LABC Feasibility Population |
| NCT00934856 (30) [back to overview] | Vss of Plasma Docetaxel |
| NCT00934856 (30) [back to overview] | Maximum Observed Concentration (Cmax) of Serum Trastuzumab Emtansine |
| NCT00934856 (30) [back to overview] | Apparent Terminal Half-Life (t1/2) of Serum Trastuzumab Emtansine |
| NCT00934856 (30) [back to overview] | Percentage of Participants With Treatment Failure - MBC Population |
| NCT00934856 (30) [back to overview] | Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Serum Trastuzumab Emtansine |
| NCT00938470 (5) [back to overview] | Percentage of Participants With Overall Clinical Tumor Response (CR or PR) |
| NCT00938470 (5) [back to overview] | Number of Participants Who Experienced a Maximum Grade of 3 or Above Adverse Event |
| NCT00938470 (5) [back to overview] | Overall Survival |
| NCT00938470 (5) [back to overview] | Percentage of Participants With Pathologic Complete Response (PCR) |
| NCT00938470 (5) [back to overview] | Disease-free Survival |
| NCT00942578 (10) [back to overview] | Count of Participants With a Radiologic Response |
| NCT00942578 (10) [back to overview] | Recommended Phase 2 Dose (RP2D) |
| NCT00942578 (10) [back to overview] | Median Time to Progression (TTP) |
| NCT00942578 (10) [back to overview] | Median Overall Survival of Patients Studied |
| NCT00942578 (10) [back to overview] | Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered the Four-Drug Combination |
| NCT00942578 (10) [back to overview] | Count of Participants With Dose-Limiting Toxicities (DLT) |
| NCT00942578 (10) [back to overview] | Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells |
| NCT00942578 (10) [back to overview] | Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells |
| NCT00942578 (10) [back to overview] | Count of Participants With Prostatic Antigen-Specific (PSA) Declines |
| NCT00942578 (10) [back to overview] | Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration |
| NCT00950300 (22) [back to overview] | Event-Free Survival (EFS) |
| NCT00950300 (22) [back to overview] | Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20) |
| NCT00950300 (22) [back to overview] | Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab |
| NCT00950300 (22) [back to overview] | Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery |
| NCT00950300 (22) [back to overview] | Overall Survival (OS) |
| NCT00950300 (22) [back to overview] | Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery |
| NCT00950300 (22) [back to overview] | Cmax of Trastuzumab After Surgery |
| NCT00950300 (22) [back to overview] | AUC21d of Trastuzumab After Surgery |
| NCT00950300 (22) [back to overview] | Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery |
| NCT00950300 (22) [back to overview] | Observed Ctrough of Trastuzumab After Surgery |
| NCT00950300 (22) [back to overview] | Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery |
| NCT00950300 (22) [back to overview] | Percentage of Participants Who Died |
| NCT00950300 (22) [back to overview] | Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery |
| NCT00950300 (22) [back to overview] | Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline |
| NCT00950300 (22) [back to overview] | Percentage of Participants With Pathological Complete Response (pCR) |
| NCT00950300 (22) [back to overview] | Percentage of Participants With Total Pathological Complete Response (tpCR) |
| NCT00950300 (22) [back to overview] | Predicted Ctrough of Trastuzumab After Surgery |
| NCT00950300 (22) [back to overview] | Percentage of Participants Who Experienced a Protocol-Defined Event |
| NCT00950300 (22) [back to overview] | Predicted Ctrough of Trastuzumab Prior to Surgery |
| NCT00950300 (22) [back to overview] | Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery |
| NCT00950300 (22) [back to overview] | Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline |
| NCT00950300 (22) [back to overview] | Tmax of Trastuzumab After Surgery |
| NCT00963807 (5) [back to overview] | Change in 18F-Fluorodeoxyglucose (FDG) Uptake |
| NCT00963807 (5) [back to overview] | Overall Response Rate Reported as a Proportion of the Total Number of Patients Who Received at Least One Cycle of Therapy Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT00963807 (5) [back to overview] | Change in FLT Uptake in Responders and Non-responders |
| NCT00963807 (5) [back to overview] | Change in FLT Uptake |
| NCT00963807 (5) [back to overview] | Change in 18F-Fluorothymidine (FLT) Uptake |
| NCT00970684 (3) [back to overview] | Best Response |
| NCT00970684 (3) [back to overview] | Progression Free Survival(PFS) |
| NCT00970684 (3) [back to overview] | Median Time to Progression |
| NCT00976989 (12) [back to overview] | Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events |
| NCT00976989 (12) [back to overview] | Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD) |
| NCT00976989 (12) [back to overview] | Efficacy: Clinical Response Rate |
| NCT00976989 (12) [back to overview] | Efficacy: Percentage of Participants Achieving Breast Conserving Surgery |
| NCT00976989 (12) [back to overview] | Efficacy: Percentage of Participants With Complete Pathological Response (pCR) |
| NCT00976989 (12) [back to overview] | Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event |
| NCT00976989 (12) [back to overview] | Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event |
| NCT00976989 (12) [back to overview] | Efficacy: Percentage of Participants Without an Overall Survival (OS) Event |
| NCT00976989 (12) [back to overview] | Efficacy: Time to Clinical Response |
| NCT00976989 (12) [back to overview] | Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures |
| NCT00976989 (12) [back to overview] | Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period |
| NCT00976989 (12) [back to overview] | Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator |
| NCT00988208 (7) [back to overview] | Time to Onset of Secondary Primary Malignancies |
| NCT00988208 (7) [back to overview] | Progression-Free Survival (PFS) |
| NCT00988208 (7) [back to overview] | Percentage of Participants With an Objective Response According to Response Evaluation Criteria in Solid Tumors - RECIST Version 1.1 Criteria |
| NCT00988208 (7) [back to overview] | Percentage of Participants Who Received Post-Study Therapies |
| NCT00988208 (7) [back to overview] | Overall Survival (OS) |
| NCT00988208 (7) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (AEs) |
| NCT00988208 (7) [back to overview] | Percentage of Participants With Secondary Primary Malignancies During the Course of the Trial |
| NCT00995761 (1) [back to overview] | Response Rates Confirmed With CT or MRI |
| NCT01012297 (4) [back to overview] | Progression-free Survival |
| NCT01012297 (4) [back to overview] | Overall Survival |
| NCT01012297 (4) [back to overview] | Objective Response Rate as Measured by RECIST 1.1 Criteria |
| NCT01012297 (4) [back to overview] | Frequency and Severity of Adverse Effects as Assessed by the CTCAE Version 4.0 |
| NCT01064479 (5) [back to overview] | Disease Control (CR + PR + Stable Disease [SD]) |
| NCT01064479 (5) [back to overview] | Overall Survival (OS) |
| 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) |
| NCT01076335 (1) [back to overview] | Number of Participants Progression Free at 1 Year |
| NCT01084655 (14) [back to overview] | Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel |
| NCT01084655 (14) [back to overview] | Phase 2: Best PSA Response |
| NCT01084655 (14) [back to overview] | Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel |
| NCT01084655 (14) [back to overview] | Phase 2: AUC 0-tau: Area Under the Plasma Concentration Versus Time Curve Zero to the Time of the End of the Dosing Interval for Orteronel |
| NCT01084655 (14) [back to overview] | Phase 2: Time to PSA Progression |
| NCT01084655 (14) [back to overview] | Phase 2: Time to Radiographic Disease Progression |
| NCT01084655 (14) [back to overview] | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE) |
| NCT01084655 (14) [back to overview] | Number of Participants With TEAEs Related to Electrocardiogram (ECG) |
| NCT01084655 (14) [back to overview] | Phase 2: Percentage of Participants With Objective Measurable Disease Response |
| NCT01084655 (14) [back to overview] | Number of Participants With TEAEs Related to Hematology and Serum Chemistry |
| NCT01084655 (14) [back to overview] | Number of Participants With TEAEs Related to Vital Signs |
| NCT01084655 (14) [back to overview] | Phase 2: Change From Baseline in Circulating Tumor Cells (CTCs) |
| NCT01084655 (14) [back to overview] | Phase 2: Percentage of Participants With Prostate-specific Antigen (PSA) Response of 30 Percent (%), 50%, and 90% |
| NCT01084655 (14) [back to overview] | Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for Orteronel |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 44 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 46 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 5 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 6 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 7 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 8 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 9 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at End of Study |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 10 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 11 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 12 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 13 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 14 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 15 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 16 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 17 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 20 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 21 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 22 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 23 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 24 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 25 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 26 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 27 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 28 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 29 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 3 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 30 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 32 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 36 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 37 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 39 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 4 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 40 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 42 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 44 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 46 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 5 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 6 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 7 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 8 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 9 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at End of Study |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 10 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 11 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 12 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 13 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 14 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 15 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 16 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 17 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 18 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 20 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 21 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 22 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 23 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 24 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 25 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 26 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 27 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 28 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 29 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 3 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 30 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 32 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 36 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 37 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 39 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 4 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 42 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 44 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 46 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 5 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 6 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 7 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at Cycle 8 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score At Cycle 9 |
| NCT01094184 (116) [back to overview] | Change From Baseline in FACT-B Score at End of Study |
| NCT01094184 (116) [back to overview] | Overall Survival |
| NCT01094184 (116) [back to overview] | Percentage of Participants Who Died Due to Any Cause |
| NCT01094184 (116) [back to overview] | Percentage of Participants With Disease Progression |
| NCT01094184 (116) [back to overview] | Time to Disease Progression |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D - Visual Analogue Scale (VAS) Score at Cycle 2 |
| NCT01094184 (116) [back to overview] | Change From Baseline in Euro Quality of Life (EQ-5D) - Health State Questionnaire Score at Cycle 2 |
| NCT01094184 (116) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Score at Cycle 2 |
| NCT01094184 (116) [back to overview] | Percentage of Participants By Karnofsky Performance Status Scale Scores |
| NCT01094184 (116) [back to overview] | Percentage of Participants By Karnofsky Performance Status Scale Scores |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D-VAS Score at Cycle 18 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 10 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 11 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 12 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 13 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 14 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 15 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 16 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 17 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 18 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 20 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 21 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 22 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 23 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 24 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 25 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 26 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 27 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 28 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 29 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 3 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 30 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 32 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 36 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 37 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 39 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 4 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 40 |
| NCT01094184 (116) [back to overview] | Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 42 |
| NCT01094288 (14) [back to overview] | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01094288 (14) [back to overview] | Terminal Phase Elimination Half-life (T1/2) for Docetaxel |
| NCT01094288 (14) [back to overview] | Overall Response Rate (ORR) Assessed for Overall Participant Population |
| NCT01094288 (14) [back to overview] | AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel |
| NCT01094288 (14) [back to overview] | AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel |
| NCT01094288 (14) [back to overview] | AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Day 7 Over the Dosing Interval for Alisertib |
| NCT01094288 (14) [back to overview] | Overall Response Rate for Prostate Cancer Participants |
| NCT01094288 (14) [back to overview] | Best Overall Response Rate Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria |
| NCT01094288 (14) [back to overview] | Best Overall Response Rate Assessed by RECIST Criteria |
| NCT01094288 (14) [back to overview] | Cmax: Maximum Observed Plasma Concentration for Alisertib |
| NCT01094288 (14) [back to overview] | Cmax: Maximum Observed Plasma Concentration for Docetaxel |
| NCT01094288 (14) [back to overview] | Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib |
| NCT01094288 (14) [back to overview] | Duration of Stable Disease (SD) |
| NCT01094288 (14) [back to overview] | Duration of Response |
| NCT01106352 (21) [back to overview] | Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4 |
| NCT01106352 (21) [back to overview] | Number of Subjects Who Responded to Interactive Voice Response System (IVRS) Pain |
| NCT01106352 (21) [back to overview] | Exploratory Efficacy: Weighted Mean Area Under the Curve for Bone Turnover Biomarkers |
| NCT01106352 (21) [back to overview] | Changes From Baseline in Weight During the Treatment Period |
| NCT01106352 (21) [back to overview] | Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period |
| NCT01106352 (21) [back to overview] | Changes From Baseline in Respiratory Rate During the Treatment Period |
| NCT01106352 (21) [back to overview] | Changes From Baseline in Heart Rate During the Treatment Period |
| NCT01106352 (21) [back to overview] | Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period |
| NCT01106352 (21) [back to overview] | Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period |
| NCT01106352 (21) [back to overview] | Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period |
| NCT01106352 (21) [back to overview] | Number of Subjects With Physical Examination During the Treatment Period |
| NCT01106352 (21) [back to overview] | Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period |
| NCT01106352 (21) [back to overview] | Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period |
| NCT01106352 (21) [back to overview] | Progression Free Survival (PFS) End Point |
| NCT01106352 (21) [back to overview] | Overall Survival Rate |
| NCT01106352 (21) [back to overview] | Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period |
| NCT01106352 (21) [back to overview] | Exploratory Efficacy: Time to Clinical or Radiographic Progression |
| NCT01106352 (21) [back to overview] | Exploratory Efficacy: Percent Change From Baseline in Circulating Tumor Cells at Day 85 |
| NCT01106352 (21) [back to overview] | Number of Subjects With Signs of Long-Term Radiation Toxicity |
| NCT01106352 (21) [back to overview] | Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part |
| NCT01106352 (21) [back to overview] | Exploratory Efficacy: Time to Prostate-specific Antigen (PSA) Progression |
| NCT01107444 (13) [back to overview] | Overall Survival (OS) |
| NCT01107444 (13) [back to overview] | Percent of Participants Having a Partial Response (PR) or a Complete Response (CR) |
| NCT01107444 (13) [back to overview] | Pharmacokinetics: Area Under the Concentration Curve From Zero to 4 Hours (AUC[0-4]) for LY2181309 and Docetaxel |
| NCT01107444 (13) [back to overview] | Progression Free Survival (PFS) |
| NCT01107444 (13) [back to overview] | Time to Documented Disease Progression |
| NCT01107444 (13) [back to overview] | Time to Worsening of Symptoms as Defined by Lung Cancer Symptom Score (LCSS) Questionnaire |
| NCT01107444 (13) [back to overview] | Time to Objective Tumor Response of Partial Response (PR) or Complete Response (CR) |
| NCT01107444 (13) [back to overview] | Number of Participants With Characterization of Toxicities as Defined by Common Terminology Criteria for Adverse Events (CTCAE) Coding |
| NCT01107444 (13) [back to overview] | Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index (ASBI) on Cycle 2 Day 1 |
| NCT01107444 (13) [back to overview] | Duration of Response |
| NCT01107444 (13) [back to overview] | Change From Baseline in Tumor Size to the End of Cycle 2 |
| NCT01107444 (13) [back to overview] | Pharmacokinetics: Area Under the Drug Concentration-Time Curve From Zero to Infinity (AUC[0 ∞]) of LY2181309 and Docetaxel |
| NCT01107444 (13) [back to overview] | Lung Cancer Symptom Scale (LCSS) Average Total Score at Cycle 2 Day 1 |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Decline of ≥2 Points From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Death or Disease Progression According to Investigator Assessment |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment |
| NCT01120184 (38) [back to overview] | Percentage of Participants With a Clinically Significant Deterioration in Health Related Quality of Life (HRQoL) as Measured by FACT Breast (FACT-B) Trial Outcome Index-Physical Function Breast (TOI-PFB) Score |
| NCT01120184 (38) [back to overview] | Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With High Human Epidermal Growth Factor Receptor 2 (HER2) Messenger Ribonucleic Acid (mRNA) Levels |
| NCT01120184 (38) [back to overview] | Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | Percentage of Participants Who Died Prior to Clinical Cutoff |
| NCT01120184 (38) [back to overview] | Percentage of Participants Who Died at 2 Years |
| NCT01120184 (38) [back to overview] | Percentage of Participants Experiencing Treatment Failure |
| NCT01120184 (38) [back to overview] | Percentage of Participants Experiencing a Clinically Significant Increase in Taxane-Related Treatment Symptoms as Measured by Taxane Subscale of the Functional Assessment of Cancer Therapy (FACT) Taxane (FACT-TaxS) Score |
| NCT01120184 (38) [back to overview] | Overall Survival Truncated at 2 Years |
| NCT01120184 (38) [back to overview] | Overall Survival (OS) at Clinical Cutoff |
| NCT01120184 (38) [back to overview] | OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | OS at Clinical Cutoff Among Those With High HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | One-Year Survival Rate |
| NCT01120184 (38) [back to overview] | Hospitalization Days |
| NCT01120184 (38) [back to overview] | Duration of Response According to IRF Assessment |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Grade 3-4 Laboratory Parameters |
| NCT01120184 (38) [back to overview] | Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module |
| NCT01120184 (38) [back to overview] | Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module |
| NCT01120184 (38) [back to overview] | Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score |
| NCT01120184 (38) [back to overview] | Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score |
| NCT01120184 (38) [back to overview] | Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score |
| NCT01120184 (38) [back to overview] | Time to Treatment Failure (TTF) |
| NCT01120184 (38) [back to overview] | Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score |
| NCT01120184 (38) [back to overview] | Progression-Free Survival (PFS) According to IRF Assessment |
| NCT01120184 (38) [back to overview] | PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | PFS According to IRF Assessment Among Those With High HER2 mRNA Levels |
| NCT01120184 (38) [back to overview] | PFS According to Investigator Assessment |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Objective Response According to IRF Assessment |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Objective Response According to Investigator Assessment |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Hospitalization |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Grade 5 Adverse Events |
| NCT01120184 (38) [back to overview] | Percentage of Participants With Grade ≥3 Adverse Events |
| NCT01126190 (4) [back to overview] | Double-Blind Phase: Number of Participants With Febrile Neutropenia |
| NCT01126190 (4) [back to overview] | Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1 |
| NCT01126190 (4) [back to overview] | Open-Label Phase: Number of Participants With Febrile Neutropenia |
| NCT01126190 (4) [back to overview] | Open-Label Phase: Duration of Severe Neutropenia in Cycle 1 |
| NCT01129206 (4) [back to overview] | Overall Response |
| NCT01129206 (4) [back to overview] | Correlation of FDG PET Response With Response Rate |
| NCT01129206 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT01129206 (4) [back to overview] | Overall Survival (OS) |
| NCT01145508 (1) [back to overview] | Overall Survival |
| NCT01168973 (9) [back to overview] | Percentage of Participants Achieving Disease Control (Disease Control Rate) |
| NCT01168973 (9) [back to overview] | Number of Participants With Anti-Ramucirumab Antibodies |
| NCT01168973 (9) [back to overview] | Progression-Free Survival (PFS) Time |
| NCT01168973 (9) [back to overview] | Change From Baseline to 30-Day Follow-Up Visit on European Quality of Life Questionnaire-5 Dimension (EQ-5D) Health State Scores |
| NCT01168973 (9) [back to overview] | Maximum and Minimum Serum Concentrations (Cmax and Cmin) of Ramucirumab |
| NCT01168973 (9) [back to overview] | Maximum Improvement on Lung Cancer Symptom Scale (LCSS) |
| NCT01168973 (9) [back to overview] | Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died |
| NCT01168973 (9) [back to overview] | Overall Survival |
| NCT01168973 (9) [back to overview] | Percentage of Participants Achieving an Objective Response (Objective Response Rate) |
| NCT01196429 (5) [back to overview] | Objective Tumor Response |
| 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] | Frequency and Severity of Toxicity |
| NCT01204697 (6) [back to overview] | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) |
| NCT01204697 (6) [back to overview] | Percentage of Participants Free From Disease Progression or Death at 6 Months |
| NCT01204697 (6) [back to overview] | Overall Survival (OS) |
| NCT01204697 (6) [back to overview] | Duration of Response (DoR) |
| NCT01204697 (6) [back to overview] | Progression-free Survival (PFS) |
| NCT01204697 (6) [back to overview] | Percentage of Participants With Disease Control |
| 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 Patients With Adverse Events (AEs) |
| NCT01220128 (28) [back to overview] | Number of Subjects With Severe Toxicities |
| NCT01220128 (28) [back to overview] | Number of Patients With Adverse Events (AEs), by CTCAE Maximum Grade Reported |
| 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 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 Alanine Aminotransferase Increased Abnormality, by Common Terminology Criteria for Adverse Events (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 Subjects With Anemia, by CTCAE Maximum Grade |
| 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 Blood Bilirubin Increased Abnormality, by CTCAE Maximum Grade |
| NCT01220128 (28) [back to overview] | Number of Subjects With Serious Adverse Events SAE(s) |
| 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 Breast Cancer Pathological Response |
| 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 Subjects With Hypercalcemia 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 Serious Adverse Events (SAEs), by CTCAE Maximum Grade Reported |
| NCT01220128 (28) [back to overview] | Number of Subjects With Hypernatremia 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 Hypokalemia 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 Creatine Increased Abnormality, by CTCAE Maximum Grade |
| 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 Hyponatremia Abnormality, by CTCAE Maximum Grade |
| 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 |
| NCT01221753 (1) [back to overview] | 4-y Overall Survival Rate |
| NCT01243775 (4) [back to overview] | Neutropenia Grade 3-4 |
| NCT01243775 (4) [back to overview] | Progression Free Survival |
| NCT01243775 (4) [back to overview] | Overall Survival |
| NCT01243775 (4) [back to overview] | Response Rate |
| NCT01250717 (1) [back to overview] | Pathologic Complete Response Was Assessed by Rigorous Pathological Examination by One of Two Pathologists |
| NCT01251653 (20) [back to overview] | Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD). |
| NCT01251653 (20) [back to overview] | Total Clearance (CL) of Docetaxel |
| NCT01251653 (20) [back to overview] | Volume of Distribution at Steady State (Vss) of Gemcitabine |
| NCT01251653 (20) [back to overview] | Best Overall Response According to RECIST v1.1 Criteria |
| NCT01251653 (20) [back to overview] | Cmax of Gemcitabine |
| NCT01251653 (20) [back to overview] | Duration of Disease Control According to RECIST v1.1 |
| NCT01251653 (20) [back to overview] | Duration of Objective Response According to RECIST v1.1 |
| NCT01251653 (20) [back to overview] | Cmax of Docetaxel |
| NCT01251653 (20) [back to overview] | Objective Response According to RECIST v1.1 |
| NCT01251653 (20) [back to overview] | AUC 0-24 of Docetaxel |
| NCT01251653 (20) [back to overview] | Cmax,ss of Afatinib |
| NCT01251653 (20) [back to overview] | The Incidence and Intensity of AEs With Grading According to CTCAE. |
| NCT01251653 (20) [back to overview] | Time to Objective Response According to RECIST v1.1 |
| NCT01251653 (20) [back to overview] | Disease Control According to RECIST v1.1 |
| NCT01251653 (20) [back to overview] | Overall Survival (OS) |
| NCT01251653 (20) [back to overview] | Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib |
| NCT01251653 (20) [back to overview] | Progression Free Survival (PFS) |
| NCT01251653 (20) [back to overview] | Total Clearance (CL) of Gemcitabine |
| NCT01251653 (20) [back to overview] | Volume of Distribution at Steady State (Vss) of Docetaxel |
| NCT01251653 (20) [back to overview] | AUC 0-tz of Gemcitabine |
| NCT01253642 (7) [back to overview] | Duration of Progression Free Survival After Initiation of Combination Phenelzine and Docetaxel Therapy |
| NCT01253642 (7) [back to overview] | Response Rate in Measurable Disease by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria |
| NCT01253642 (7) [back to overview] | Time to Death From All Causes |
| NCT01253642 (7) [back to overview] | Toxicity of the Regimen |
| NCT01253642 (7) [back to overview] | Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30% |
| NCT01253642 (7) [back to overview] | Maximum Change in PSA |
| NCT01253642 (7) [back to overview] | Frequency of MAOA (Monoamine Oxidase A) Overexpression in CRPC (Castration-Resistant Prostate Cancer) Tumors That Are Progressing on Docetaxel |
| NCT01256567 (7) [back to overview] | Half Life (t 1/2) of Ramucirumab |
| NCT01256567 (7) [back to overview] | Maximum Concentration (Cmax) of Ramucirumab |
| NCT01256567 (7) [back to overview] | Number of Participants With Adverse Events |
| NCT01256567 (7) [back to overview] | Steady State Volume of Distribution (Vss) of Ramucirumab |
| NCT01256567 (7) [back to overview] | Serum Anti-IMC-1121B Antibody Assessment (Immunogenicity) |
| NCT01256567 (7) [back to overview] | Area Under the Curve (AUC) of Ramucirumab |
| NCT01256567 (7) [back to overview] | Clearance (Cl) of Ramucirumab |
| NCT01275677 (7) [back to overview] | Toxicity Assessed by Adverse Events |
| NCT01275677 (7) [back to overview] | Percentage of Patients Alive and Recurrence-Free (RFI) |
| NCT01275677 (7) [back to overview] | Percentage of Patients Alive and Free From Invasive Disease (IDFS) |
| NCT01275677 (7) [back to overview] | Percentage of Patients Alive and Free From Distant Recurrence (DRFI) |
| NCT01275677 (7) [back to overview] | Percentage of Patients Alive and Free From Breast Cancer (BCFS) |
| NCT01275677 (7) [back to overview] | Percentage of Patients Alive and Disease-Free (DFS-DCIS) |
| NCT01275677 (7) [back to overview] | Percentage of Patients Alive (Overall Survival) |
| NCT01282463 (9) [back to overview] | Duration of Response |
| NCT01282463 (9) [back to overview] | Number of Participants With Serum Anti-Ramucirumab Antibody Assessment |
| NCT01282463 (9) [back to overview] | Percentage of Participants Achieving Objective Response Rate (ORR) |
| NCT01282463 (9) [back to overview] | Pharmacokinetics (PK) Maximum Concentration (Cmax) Ramucirumab |
| NCT01282463 (9) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT01282463 (9) [back to overview] | Progression-Free Survival (PFS) |
| NCT01282463 (9) [back to overview] | PK: Minimum Concentration (Cmin) Ramucirumab |
| NCT01282463 (9) [back to overview] | PK: Cmin Icrucumab |
| NCT01282463 (9) [back to overview] | PK: Cmax Icrucumab |
| NCT01284335 (8) [back to overview] | Number of Participants With a Clinically Significant Effects |
| NCT01284335 (8) [back to overview] | Number of Participants With Dose-Limiting Toxicities Cycle 1 |
| NCT01284335 (8) [back to overview] | PK: Area Under the Curve Albumin (AUCalb) |
| NCT01284335 (8) [back to overview] | Pharmacokinetic (PK): Concentration Maximum (Cmax) |
| NCT01284335 (8) [back to overview] | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) |
| NCT01284335 (8) [back to overview] | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) |
| NCT01284335 (8) [back to overview] | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) |
| NCT01284335 (8) [back to overview] | Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response) |
| NCT01285635 (5) [back to overview] | Median Progression Free Survival in Months |
| NCT01285635 (5) [back to overview] | Median Overall Survival in Months |
| NCT01285635 (5) [back to overview] | Median Duration of Response For All Groups Combined |
| NCT01285635 (5) [back to overview] | Incidence of Grade 3 and 4 Toxicities by Arm |
| NCT01285635 (5) [back to overview] | Number of Patients With a Complete Response (CR) and Partial Response (PR) |
| NCT01301729 (7) [back to overview] | Clinical Benefit Rate |
| NCT01301729 (7) [back to overview] | Duration of Response |
| NCT01301729 (7) [back to overview] | Overall Response Rate |
| NCT01301729 (7) [back to overview] | Overall Survival |
| NCT01301729 (7) [back to overview] | Percentage of Participants With an Adverse Event (AE) |
| NCT01301729 (7) [back to overview] | Time to Progression |
| NCT01301729 (7) [back to overview] | Progression-Free Survival (PFS) |
| NCT01308567 (11) [back to overview] | Time to Tumor Progression Free Survival |
| NCT01308567 (11) [back to overview] | Overall Survival (OS) |
| NCT01308567 (11) [back to overview] | Time to Prostate Serum Antigen Progression Free Survival (PSA-PFS) |
| NCT01308567 (11) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL |
| NCT01308567 (11) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score as a Measure of Health Related Quality of Life (HRQoL) |
| NCT01308567 (11) [back to overview] | Percentage of Participants With Overall Objective Tumor Response |
| NCT01308567 (11) [back to overview] | Time to Pain Progression Free Survival (Pain PFS) |
| NCT01308567 (11) [back to overview] | Skeletal Related Events (SRE) Free Survival |
| NCT01308567 (11) [back to overview] | Progression Free Survival (PFS) |
| NCT01308567 (11) [back to overview] | Percentage of Participants With PSA Response |
| NCT01308567 (11) [back to overview] | Percentage of Participants With Pain Response |
| NCT01351415 (8) [back to overview] | Time to Progression (TTP) According to RECIST v1.1 |
| NCT01351415 (8) [back to overview] | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |
| NCT01351415 (8) [back to overview] | Percentage of Participants Who Are Alive at Month 6, 12, and 18 |
| NCT01351415 (8) [back to overview] | Percentage of Participants With Objective Response According to RECIST v1.1 |
| NCT01351415 (8) [back to overview] | Percentage of Participants With Disease Control According to RECIST v1.1 |
| NCT01351415 (8) [back to overview] | Overall Survival (OS) |
| NCT01351415 (8) [back to overview] | Duration of Response (DoR) According to RECIST v1.1 |
| NCT01351415 (8) [back to overview] | Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
| 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] | 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 |
| 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] | 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 IDFS Event-Free (Excluding SPNBC) at Year 3, as Assessed Using Radiologic, Histologic Examinations or Laboratory Findings |
| NCT01358877 (30) [back to overview] | Trough Serum Concentration (Cmin) of Pertuzumab |
| 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: Anxiety/Depression Domain |
| NCT01358877 (30) [back to overview] | Percentage of Participants With Primary Cardiac Event |
| 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] | Change From Baseline in EORTC QLQ-C30 Financial Difficulties Subscale Scores |
| NCT01358877 (30) [back to overview] | Percentage of Participants With Response for EQ-5D-3L Questionnaire: Self-Care Domain |
| NCT01358877 (30) [back to overview] | Change From Baseline in EORTC QLQ-BR23 Symptom Scale Score |
| NCT01358877 (30) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Who Were Alive at Year 3 |
| 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] | 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] | Change From Baseline in EORTC QLQ-C30 Disease/Treatment-Related Symptoms Subscale Scores |
| 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] | Peak Serum Concentration (Cmax) of Pertuzumab |
| 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 Who Died |
| 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 |
| NCT01362296 (20) [back to overview] | Change From Baseline in Heart Rate: Randomized Phase |
| NCT01362296 (20) [back to overview] | Change From Baseline in Heart Rate: Crossover Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With Any SAE or Non-serious AE: Crossover Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase |
| NCT01362296 (20) [back to overview] | GSK1120212 Plasma Pharmacokinetic (PK) Concentration |
| NCT01362296 (20) [back to overview] | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase |
| NCT01362296 (20) [back to overview] | Change From Baseline in SBP and DBP: Crossover Phase |
| NCT01362296 (20) [back to overview] | Progression-Free Survival (PFS) as Assessed by the Investigator (INV) |
| NCT01362296 (20) [back to overview] | Overall Survival (OS) |
| NCT01362296 (20) [back to overview] | Duration of Response (DOR) as Assessed by the Investigator: Randomized Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase |
| NCT01362296 (20) [back to overview] | Number of Participants With Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase |
| NCT01376310 (1) [back to overview] | Number of Participants With Adverse Events |
| NCT01395758 (4) [back to overview] | Overall Survival (OS) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy. |
| NCT01395758 (4) [back to overview] | Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy. |
| NCT01395758 (4) [back to overview] | ORR Among Subjects in the Crossover Period Treated With Erlotinib Plus Tivantinib |
| NCT01395758 (4) [back to overview] | Objective Response Rate (ORR) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy. |
| NCT01418001 (1) [back to overview] | Overall Objective Response |
| NCT01437449 (4) [back to overview] | Progression-free Survival (PFS) |
| NCT01437449 (4) [back to overview] | Grade 3, 4, and 5 Related Adverse Events (Toxicities) |
| NCT01437449 (4) [back to overview] | Overall Response Rate (ORR) |
| NCT01437449 (4) [back to overview] | Overall Survival (OS) |
| NCT01443078 (2) [back to overview] | Pathologic Response Rate |
| NCT01443078 (2) [back to overview] | PERCIST Partial Metabolic Response |
| NCT01446016 (4) [back to overview] | Time of Overall Survival (OS) |
| NCT01446016 (4) [back to overview] | Overall Response Rate (ORR) |
| NCT01446016 (4) [back to overview] | Time to Progression Free Survival (PFS) |
| NCT01446016 (4) [back to overview] | Number of Patients Who Experienced Grade 3 of Greater Adverse Events |
| NCT01454934 (3) [back to overview] | Objective Response Rate (ORR) |
| NCT01454934 (3) [back to overview] | Overall Survival (OS) |
| NCT01454934 (3) [back to overview] | Progression Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT01459614 (5) [back to overview] | Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity |
| NCT01459614 (5) [back to overview] | Overall Survival (OS) |
| NCT01459614 (5) [back to overview] | Percentage of Participants Without Disease Progression (Progression-Free Survival) at 6 Months |
| NCT01459614 (5) [back to overview] | Progression-free Survival (PFS) |
| NCT01459614 (5) [back to overview] | Disease Control Rate (DCR) |
| NCT01468532 (9) [back to overview] | Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 |
| NCT01468532 (9) [back to overview] | Time to Progression (TTP) |
| NCT01468532 (9) [back to overview] | Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy |
| NCT01468532 (9) [back to overview] | Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy |
| NCT01468532 (9) [back to overview] | Percentage Prostate-specific Antigen (PSA) Change Noted |
| NCT01468532 (9) [back to overview] | Pharmacokinetics (PK) of SOM230 |
| NCT01468532 (9) [back to overview] | The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0 |
| NCT01468532 (9) [back to overview] | Measurements of Tumor Using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria Before and After Treatment With the Combination of Pasireotide in Combination With Docetaxel |
| NCT01468532 (9) [back to overview] | Overall Survival (OS) |
| NCT01498289 (6) [back to overview] | PFS in Low-ERCC1 Participants |
| NCT01498289 (6) [back to overview] | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT01498289 (6) [back to overview] | PFS Variation by ERCC1 |
| NCT01498289 (6) [back to overview] | Overall Survival (OS) |
| NCT01498289 (6) [back to overview] | Overall Response Rate (ORR) |
| NCT01498289 (6) [back to overview] | Progression-free Survival (PFS) in High-ERCC1 Patients |
| NCT01515748 (10) [back to overview] | Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3 |
| NCT01515748 (10) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
| NCT01515748 (10) [back to overview] | Overall Survival (OS) |
| NCT01515748 (10) [back to overview] | Percentage of Participants With 3-Year Progression-Free Survival (PFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1 |
| NCT01515748 (10) [back to overview] | Percentage of Participants With R0 Resection |
| NCT01515748 (10) [back to overview] | Number of Participants With Post-Operative Pathological Stage Response |
| NCT01515748 (10) [back to overview] | Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 |
| NCT01515748 (10) [back to overview] | Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 |
| NCT01515748 (10) [back to overview] | Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 |
| NCT01515748 (10) [back to overview] | Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 |
| NCT01527487 (4) [back to overview] | Pathologic Complete Response (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery |
| NCT01527487 (4) [back to overview] | The Number of Adverse Events as a Measure of Safety and Tolerability. |
| NCT01527487 (4) [back to overview] | Disease-Free Survival (DFS) at 2 Years |
| NCT01527487 (4) [back to overview] | Clinical Response Rate (cRR) of ErC as Neoadjuvant Therapy |
| NCT01533207 (3) [back to overview] | Number of Participants With Recurrence |
| NCT01533207 (3) [back to overview] | Number of Participants Who Experienced Death |
| NCT01533207 (3) [back to overview] | Incidence of Grade 3 or Higher Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 |
| NCT01557959 (3) [back to overview] | Time to Progression |
| NCT01557959 (3) [back to overview] | Response Rate Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood |
| NCT01557959 (3) [back to overview] | Median Survival Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood |
| NCT01567163 (7) [back to overview] | Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 2 |
| NCT01567163 (7) [back to overview] | Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Docetaxel |
| NCT01567163 (7) [back to overview] | Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies |
| NCT01567163 (7) [back to overview] | Pharmacokinetics: Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Docetaxel |
| NCT01567163 (7) [back to overview] | Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 1 |
| NCT01567163 (7) [back to overview] | Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 2 |
| NCT01567163 (7) [back to overview] | Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 1 |
| NCT01572038 (58) [back to overview] | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Number of Participants Who Died Over the Course of the Study by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term) |
| NCT01572038 (58) [back to overview] | Number of Participants Who Died Within 6 Months of Starting Study Treatment by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term) |
| NCT01572038 (58) [back to overview] | Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events That Were Related to Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.5% of Participants by Preferred Term |
| NCT01572038 (58) [back to overview] | Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events to Monitor, Occurring in ≥0.5% of Participants by Category and Preferred Term |
| NCT01572038 (58) [back to overview] | Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria |
| NCT01572038 (58) [back to overview] | Change From Baseline in FACT-B Questionnaire Breast Cancer Subscale Score Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Region of Enrollment: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Number of Participants With a Congestive Heart Failure Event |
| NCT01572038 (58) [back to overview] | Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events, Occurring in ≥1% of Participants by System Organ Class and Preferred Term |
| NCT01572038 (58) [back to overview] | Number of Participants by Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Categories Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Visceral Disease at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Taxane Chemotherapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), TEAEs Leading to Death, Grade ≥3 TEAEs, Any-Grade and Grade ≥3 TEAEs Related to Pertuzumab, and TEAEs to Monitor |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Region of Enrollment: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Previous Trastuzumab Therapy: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Hormone Receptor Status at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by ECOG Performance Status at Baseline: Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), Grade ≥3 TEAEs, and Grade ≥3 TEAEs Related to Pertuzumab |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Age (≤65 vs. >65 Years): Overview of the Number of Participants With Serious Treatment-Emergent Adverse Events (TEAEs), TEAEs Leading to Death, Grade ≥3 TEAEs, Any-Grade and Grade ≥3 TEAEs Related to Pertuzumab, and TEAEs to Monitor |
| NCT01572038 (58) [back to overview] | Percentage of Participants by Best Overall Response as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Overview of the Number of Participants With at Least One Treatment-Emergent Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0) |
| NCT01572038 (58) [back to overview] | Change From Baseline in FACT-B Questionnaire Emotional Well-Being Subscale Score Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Change From Baseline in FACT-B Questionnaire Functional Well-Being Subscale Score Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Change From Baseline in FACT-B Questionnaire Physical Well-Being Subscale Score Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Change From Baseline in FACT-B Questionnaire Social Well-Being Subscale Score Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events to Monitor of Any Grade, Occurring in ≥5% of Participants by Category |
| NCT01572038 (58) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B) Questionnaire Total Score Over the Course of the Study |
| NCT01572038 (58) [back to overview] | Clinical Benefit Rate (CR or PR, or SD for at Least 6 Months) Based on Best Overall Response as Assessed by the Investigator Using RECIST v.1.1 |
| NCT01572038 (58) [back to overview] | Duration of Response as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Overall Survival |
| NCT01572038 (58) [back to overview] | Progression-Free Survival, as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Age (≤65 vs. >65 Years): Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by ECOG Performance Status at Baseline: Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by ECOG Performance Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Hormone Receptor Status at Baseline: Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Hormone Receptor Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Previous Trastuzumab Therapy: Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Previous Trastuzumab Therapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Region of Enrollment: Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Taxane Chemotherapy: Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Taxane Chemotherapy: Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Taxane Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Visceral Disease at Baseline: Overall Survival |
| NCT01572038 (58) [back to overview] | Subgroup Analysis by Visceral Disease at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Time to Onset of the First Episode of Congestive Heart Failure |
| NCT01572038 (58) [back to overview] | Time to Response for Participants With Best Overall Response of Complete Response or Partial Response, as Assessed by the Investigator Using RECIST v1.1 |
| NCT01572038 (58) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events Leading to Discontinuation of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.2% of Participants by Preferred Term |
| NCT01572038 (58) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events of Special Interest by Category and Preferred Term |
| NCT01572038 (58) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events of Any Grade That Were Related to Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥10% of Participants by System Organ Class |
| NCT01572038 (58) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events Leading to Dose Interruption of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.5% of Participants by Preferred Term |
| NCT01572038 (58) [back to overview] | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria |
| NCT01572038 (58) [back to overview] | Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0 |
| NCT01574716 (6) [back to overview] | Part 2: Number of Participants Who Had Relationship Between MORAb-004 Exposures and Biomarker Levels |
| NCT01574716 (6) [back to overview] | Part 2: Overall Response Rate (ORR) |
| NCT01574716 (6) [back to overview] | Part 2: Overall Survival (OS) |
| NCT01574716 (6) [back to overview] | Part 2: Radiologic Progression-free Survival (PFS) |
| NCT01574716 (6) [back to overview] | Part 2: Radiologic Progression-free Survival Rate (PFR) |
| NCT01574716 (6) [back to overview] | Part 2: Symptomatic Progression-free Survival |
| NCT01593748 (4) [back to overview] | Average Score of Quality of Life |
| NCT01593748 (4) [back to overview] | Rate of Participants With Grade 3 or Higher Toxicity |
| NCT01593748 (4) [back to overview] | Hazard Ratio |
| NCT01593748 (4) [back to overview] | Average Number of Months of Progression-free Survival |
| NCT01603420 (7) [back to overview] | Assessment of Total Number of Survival Events With Comparison of Group Arms |
| NCT01603420 (7) [back to overview] | Assessment of Total Number of Local/Distant Failures |
| NCT01603420 (7) [back to overview] | Assessment of Total Number of Biochemical Failure Events |
| NCT01603420 (7) [back to overview] | Assessment of Number of Grade 2 or Higher Genitourinary (GU) and Gastrointestinal (GI) Adverse Events |
| NCT01603420 (7) [back to overview] | Phase 2 - Cumulative Number of Incidences of Grade 3 or Higher Adverse Events. |
| NCT01603420 (7) [back to overview] | Assessment of Total Number of Salvage Androgen Deprivation Use With Comparison of Arms. |
| NCT01603420 (7) [back to overview] | Phase 2 - Assessment of Number of Freedom From Failure Events in the Chemotherapy Arm |
| NCT01633541 (7) [back to overview] | Functional Assessment 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] | Voice Related QOL |
| NCT01633541 (7) [back to overview] | Number of Patients Alive and Free From Indication for Laryngectomy Three Months Post Treatment |
| NCT01633541 (7) [back to overview] | Head and Neck Related Quality of Life (QOL) |
| NCT01633541 (7) [back to overview] | Progression-free Survival |
| NCT01639131 (3) [back to overview] | Progression-free Survival (PFS) |
| NCT01639131 (3) [back to overview] | Response Rate |
| NCT01639131 (3) [back to overview] | Overall Survival With Gemcitabine and Docetaxel Combination Therapy |
| NCT01642004 (14) [back to overview] | Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants |
| NCT01642004 (14) [back to overview] | Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants |
| NCT01642004 (14) [back to overview] | Overall Survival (OS) Rate in All Randomized Participants - Extended Collection |
| NCT01642004 (14) [back to overview] | Overall Survival (OS) Rate in All Randomized Participants |
| NCT01642004 (14) [back to overview] | Progression-Free Survival (PFS) Time in Months for All Randomized Participants |
| NCT01642004 (14) [back to overview] | Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants |
| NCT01642004 (14) [back to overview] | Progression Free Survival Rate (PFSR) |
| NCT01642004 (14) [back to overview] | Time To Response (TTR) in Months for All Confirmed Responders |
| NCT01642004 (14) [back to overview] | Duration of Objective Response (DOR) in Months for All Confirmed Responders |
| NCT01642004 (14) [back to overview] | Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint |
| NCT01642004 (14) [back to overview] | Objective Response Rate (ORR) in All Randomized Participants |
| NCT01642004 (14) [back to overview] | Overall Survival (OS) Time in Months for All Randomized Participants - Extended Collection |
| NCT01642004 (14) [back to overview] | Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint |
| NCT01642004 (14) [back to overview] | Percentage of Participants Experiencing Disease-related Symptom Improvement by Week 12 |
| NCT01646125 (2) [back to overview] | Progression Free Survival (PFS) |
| NCT01646125 (2) [back to overview] | Overall Response Rate (ORR) |
| NCT01652469 (3) [back to overview] | Number of Participants With Adverse Events |
| NCT01652469 (3) [back to overview] | Progression-free Survival |
| NCT01652469 (3) [back to overview] | Overall Survival |
| NCT01653158 (31) [back to overview] | Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 4 |
| NCT01653158 (31) [back to overview] | Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 4 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 1 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 4 |
| NCT01653158 (31) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 1 |
| NCT01653158 (31) [back to overview] | Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 4 |
| NCT01653158 (31) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 1 |
| NCT01653158 (31) [back to overview] | Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 1 |
| NCT01653158 (31) [back to overview] | Observed Accumulation Ratio (Rac) of CP-751,871 |
| NCT01653158 (31) [back to overview] | Recommended Phase 2 Dose (RP2D) |
| NCT01653158 (31) [back to overview] | Systemic Clearance (CL) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Systemic Clearance (CL) of CP-751,871 in Cycle 4 |
| NCT01653158 (31) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4 |
| NCT01653158 (31) [back to overview] | Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871 |
| NCT01653158 (31) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 4 |
| NCT01653158 (31) [back to overview] | Volume of Distribution (Vz) of CP-751,871 in Cycle 1 |
| NCT01653158 (31) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT01653158 (31) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 4 |
| NCT01653158 (31) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 1 |
| NCT01653158 (31) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4 |
| NCT01671319 (2) [back to overview] | Incidence of Febrile Neutropenia |
| NCT01671319 (2) [back to overview] | Feasibility for Dose-dense TC Therapy: Number of Participants Receiving at Least 90% of Total Dose of Therapy |
| NCT01671332 (5) [back to overview] | Overall Survival |
| NCT01671332 (5) [back to overview] | Number of Participants With Toxicity/Adverse Events From Treatment |
| NCT01671332 (5) [back to overview] | Evaluation of Peripheral Blood Lymphocytes for DNA Damage-induced Checkpoint Control. |
| NCT01671332 (5) [back to overview] | Progression-free Survival in Months |
| NCT01671332 (5) [back to overview] | Response Rate Per RECIST 1.1 Criteria |
| NCT01673867 (9) [back to overview] | Objective Response Rate (ORR) by PD-L1 Expression at Baseline |
| NCT01673867 (9) [back to overview] | Duration of Objective Response (DOOR) |
| NCT01673867 (9) [back to overview] | Overall Survival (OS) - Extended Collection |
| NCT01673867 (9) [back to overview] | Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint |
| NCT01673867 (9) [back to overview] | Percentage of Participants Experiencing Disease-Related Symptom Improvement by Week 12 |
| NCT01673867 (9) [back to overview] | Progression-Free Survival (PFS) |
| NCT01673867 (9) [back to overview] | Overall Survival (OS) by PD-L1 Expression at Baseline |
| NCT01673867 (9) [back to overview] | Time To Objective Response (TTOR) |
| NCT01673867 (9) [back to overview] | Objective Response Rate (ORR) |
| NCT01683994 (5) [back to overview] | Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) |
| NCT01683994 (5) [back to overview] | Progression Free Survival (PFS) of Cabozantinib + Docetaxel + Prednisone Compared to Docetaxel + Prednisone Alone |
| NCT01683994 (5) [back to overview] | Number of Participants Achieving Prostatic-Specific Antigen (PSA) Decline of 30% or 50% From Baseline |
| NCT01683994 (5) [back to overview] | Number of Participants With a Dose Limiting Toxicities (DLTs) |
| NCT01683994 (5) [back to overview] | Maximum Tolerated Dose (MTD) |
| NCT01703091 (6) [back to overview] | Overall Survival (OS) |
| NCT01703091 (6) [back to overview] | Change From Baseline in Lung Cancer Symptom Scale (LCSS) |
| NCT01703091 (6) [back to overview] | Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score |
| NCT01703091 (6) [back to overview] | Progression-Free Survival (PFS) |
| NCT01703091 (6) [back to overview] | Percentage of Participants Who Achieved Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [Objective Tumor Response Rate (ORR)] |
| NCT01703091 (6) [back to overview] | Percentage of Participants Who Achieved Best Overall Disease Response of CR, PR or Stable Disease (SD) [Disease Control Rate (DCR)] |
| NCT01715233 (3) [back to overview] | Overall Survival |
| NCT01715233 (3) [back to overview] | CHFR Methylation Status |
| NCT01715233 (3) [back to overview] | Response |
| NCT01718353 (9) [back to overview] | PSA Progression Free Survival |
| NCT01718353 (9) [back to overview] | Radiographic Progression-free Survival (rPFS) |
| NCT01718353 (9) [back to overview] | Progression Free Survival (PFS) |
| NCT01718353 (9) [back to overview] | Percentage of Participants With PSA Response |
| NCT01718353 (9) [back to overview] | Percentage of Participants With ≥30% and ≥50% Reduction in PSA Response |
| NCT01718353 (9) [back to overview] | Clinical Progression-free Survival (cPFS) |
| NCT01718353 (9) [back to overview] | Overall Survival |
| NCT01718353 (9) [back to overview] | Drug-target Engagement in CTCs: Change From Baseline at Cycle 1 Day 8 in MTB by Categories of PSA Decrease From Baseline (≥30%, Not ≥30%) After Cycle 4 |
| NCT01718353 (9) [back to overview] | Drug-target Engagement in Circulating Tumor Cells (CTCs): Change From Baseline at Cycle 1 Day 8 in Percent Androgen Receptor Nuclear Localization (%ARNL) by Categories of PSA Decrease From Baseline (≥50%, Not ≥50%) After Cycle 4 |
| NCT01724866 (28) [back to overview] | Absolute ANC Nadir Overtime in Cycle 2 |
| NCT01724866 (28) [back to overview] | Depth of ANC Nadir in Cycle 4 |
| NCT01724866 (28) [back to overview] | Duration of DSN in Cycle 3 |
| NCT01724866 (28) [back to overview] | Depth of ANC Nadir in Cycle 3 |
| NCT01724866 (28) [back to overview] | Depth of ANC Nadir in Cycle 2 |
| NCT01724866 (28) [back to overview] | Depth of ANC Nadir in Cycle 1 |
| NCT01724866 (28) [back to overview] | Time to ANC Recovery in Cycle 4 |
| NCT01724866 (28) [back to overview] | Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312) |
| NCT01724866 (28) [back to overview] | Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1 |
| NCT01724866 (28) [back to overview] | Absolute ANC Nadir Overtime in Cycle 4 |
| NCT01724866 (28) [back to overview] | Duration of Severe Neutropenia (DSN) in Cycle 1 |
| NCT01724866 (28) [back to overview] | Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities |
| NCT01724866 (28) [back to overview] | Time to Reach Maximum Concentration of SPI-2012 (Tmax) |
| NCT01724866 (28) [back to overview] | Time to ANC Recovery in Cycle 3 |
| NCT01724866 (28) [back to overview] | Time to ANC Recovery in Cycle 2 |
| NCT01724866 (28) [back to overview] | Time to ANC Recovery in Cycle 1 |
| NCT01724866 (28) [back to overview] | Time to ANC Nadir in Cycle 1 |
| NCT01724866 (28) [back to overview] | Time to ANC Nadir in Cycle 4 |
| NCT01724866 (28) [back to overview] | Duration of DSN in Cycle 4 |
| NCT01724866 (28) [back to overview] | Time to ANC Nadir in Cycle 3 |
| NCT01724866 (28) [back to overview] | Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4 |
| NCT01724866 (28) [back to overview] | Time to ANC Nadir in Cycle 2 |
| NCT01724866 (28) [back to overview] | Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4 |
| NCT01724866 (28) [back to overview] | Maximum Concentration of SPI-2012 (Cmax) |
| NCT01724866 (28) [back to overview] | Number of Participants With Positive Antibodies for SPI-2012 |
| NCT01724866 (28) [back to overview] | Half-life of SPI-2012 (t1/2) |
| NCT01724866 (28) [back to overview] | Absolute ANC Nadir Overtime in Cycle 3 |
| NCT01724866 (28) [back to overview] | Duration of DSN in Cycle 2 |
| NCT01750281 (2) [back to overview] | Overall Survival (OS) |
| NCT01750281 (2) [back to overview] | Progression Free Survival (PFS) |
| NCT01754623 (2) [back to overview] | Margin-negative (R0) Resection Rate |
| NCT01754623 (2) [back to overview] | Overall Survival (OS) Rate |
| NCT01777945 (7) [back to overview] | Clinical Benefit Rate |
| NCT01777945 (7) [back to overview] | Time to Treatment Failure |
| NCT01777945 (7) [back to overview] | Progression-free Survival (PFS) |
| NCT01777945 (7) [back to overview] | Percentage of Capecitabine Dose Modifications |
| NCT01777945 (7) [back to overview] | Duration of Treatment With Xeloda |
| NCT01777945 (7) [back to overview] | Overall Response Rate |
| NCT01777945 (7) [back to overview] | Number of Participants With Adverse Events |
| NCT01779050 (2) [back to overview] | Death Rate |
| NCT01779050 (2) [back to overview] | Number of Participants With Disease Recurrence |
| NCT01780545 (3) [back to overview] | Overall Survival |
| NCT01780545 (3) [back to overview] | Overall Survival (OS) According to Baseline Serum Hsp27 Level. |
| NCT01780545 (3) [back to overview] | Safety and Toxicity of Regimen |
| NCT01794845 (2) [back to overview] | Overall Response Rate (ORR) of Participants |
| NCT01794845 (2) [back to overview] | Number of Study Participants Experiencing Treatment-Related Toxicity |
| NCT01798485 (10) [back to overview] | Objective Response Rate (ORR) as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Kaplan-Meier Estimate of Duration of Response (DOR) as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Kaplan-Meier Estimate for Time to Emergence of New Metastatic Lesion (TNL) as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Progression Free Survival (PFS) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Participants With Treatment-Emergent Adverse Events as of 23 December 2015 |
| NCT01798485 (10) [back to overview] | Disease Control Rate (DCR) as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Progression-free Survival (PFS) as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Percentage of Participants With Progressive Disease Due to Any New Metastatic Lesion as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Overall Survival as of 19 October 2015 |
| NCT01798485 (10) [back to overview] | Overall Survival (OS) In Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015 |
| NCT01824901 (1) [back to overview] | Maximum Tolerated Dose (MTD) of FGFR Inhibitor AZD4547 |
| NCT01828112 (1) [back to overview] | Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC) |
| 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 Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
| NCT01862328 (8) [back to overview] | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 |
| NCT01862328 (8) [back to overview] | Percentage of Participants With Objective Response |
| NCT01862328 (8) [back to overview] | MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924 |
| NCT01862328 (8) [back to overview] | Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings |
| NCT01862328 (8) [back to overview] | Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924 |
| NCT01862328 (8) [back to overview] | Duration of Response |
| NCT01868022 (23) [back to overview] | Number of Participants With Dose Reduction |
| NCT01868022 (23) [back to overview] | Number of Participants With Dose Delays |
| NCT01868022 (23) [back to overview] | Change From Baseline in Temperature |
| NCT01868022 (23) [back to overview] | Change From Baseline in Heart Rate |
| NCT01868022 (23) [back to overview] | Number of Participants With the Abnormal Urinalysis Findings |
| 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 Non-serious Adverse Events (AEs) and Serious AEs (SAEs) |
| NCT01868022 (23) [back to overview] | Progression Free Survival (PFS) as Assessed by Investigator |
| 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 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 Withdrew Due to AEs |
| NCT01868022 (23) [back to overview] | Number of Participants With Overall Response Rate (ORR) |
| 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 Dose-Limiting Toxicities (DLT) |
| 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] | 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 |
| NCT01869192 (2) [back to overview] | Pathological Response |
| NCT01869192 (2) [back to overview] | Overall Response Rate |
| NCT01876251 (23) [back to overview] | Ctrough of PF-03084014 in the Expansion Cohort |
| NCT01876251 (23) [back to overview] | Maximum Serum or Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of PF-03084014 in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Cmax of PF-03084014 in the Expansion Cohort |
| NCT01876251 (23) [back to overview] | Cmax of Docetaxel in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | AUClast of PF-03084014 in the Expansion Cohort |
| NCT01876251 (23) [back to overview] | AUClast and AUC From Time 0 Extrapolated to Infinite Time (AUCinf) of Docetaxel in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Measured Concentration (AUClast) of PF-03084014 in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Progression-free Survival (PFS) at 6 Months - Expansion Cohort |
| NCT01876251 (23) [back to overview] | Percentage of Participants With Objective Response (OR) |
| NCT01876251 (23) [back to overview] | Number of Participants With Laboratory Abnormalities |
| NCT01876251 (23) [back to overview] | Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1 |
| NCT01876251 (23) [back to overview] | Duration of Response (DR) |
| NCT01876251 (23) [back to overview] | Volume of Distribution (Vss) of Docetaxel in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Tmax of PF-03084014 in the Expansion Cohort |
| NCT01876251 (23) [back to overview] | Tmax of Docetaxel in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Time to Cmax (Tmax) of PF-03084014 in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Terminal Half-life (t1/2) of Docetaxel in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Systemic Clearance (CL) of Docetaxel in Dose-finding Cohort |
| NCT01876251 (23) [back to overview] | Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood |
| NCT01876251 (23) [back to overview] | Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood |
| NCT01876251 (23) [back to overview] | Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood |
| NCT01876251 (23) [back to overview] | Number of Participants With QTc Values Meeting Categorical Summarization Criteria |
| NCT01876251 (23) [back to overview] | Number of Participants With All Causality and Treatment-related Treatment-emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Withdrawals Due to TEAEs |
| NCT01879085 (8) [back to overview] | Six-month Progression-free Survival (PFS) |
| NCT01879085 (8) [back to overview] | Six-month Overall Survival (OS) |
| NCT01879085 (8) [back to overview] | Objective Response Rate (ORR) |
| NCT01879085 (8) [back to overview] | Progression-free Survival (PFS) |
| NCT01879085 (8) [back to overview] | Phase I: Recommended Phase II Dose of Vorinostat |
| NCT01879085 (8) [back to overview] | Overall Survival (OS) |
| NCT01879085 (8) [back to overview] | One-year Progression-free Survival (PFS) |
| NCT01879085 (8) [back to overview] | One-year Overall Survival (OS) |
| NCT01882985 (1) [back to overview] | Time to PSA Progression |
| NCT01903993 (7) [back to overview] | DOR (Modified RECIST) |
| NCT01903993 (7) [back to overview] | Duration of Response (DOR) |
| NCT01903993 (7) [back to overview] | Objective Response Rate (ORR) |
| NCT01903993 (7) [back to overview] | ORR (Modified RECIST) |
| NCT01903993 (7) [back to overview] | Overall Survival (OS) |
| NCT01903993 (7) [back to overview] | PFS (Modified RECIST) |
| NCT01903993 (7) [back to overview] | Progression-Free Survival (PFS) |
| NCT01905657 (6) [back to overview] | Percentage of Participants Discontinuing Study Drug Due to AEs |
| NCT01905657 (6) [back to overview] | Percentage of Participants Experiencing Adverse Events (AEs) |
| NCT01905657 (6) [back to overview] | Duration of Response (DOR) by RECIST 1.1 |
| NCT01905657 (6) [back to overview] | Overall Response Rate (ORR) by RECIST 1.1 |
| NCT01905657 (6) [back to overview] | Overall Survival (OS) |
| NCT01905657 (6) [back to overview] | Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
| NCT01920061 (80) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B) |
| NCT01920061 (80) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A) |
| NCT01920061 (80) [back to overview] | Number of Participants With Maximum Increase From Baseline in Corrected QT (QTc) Interval |
| NCT01920061 (80) [back to overview] | Number of Participants With Maximum Corrected QT (QTc) Interval Meeting Pre-defined Criteria |
| NCT01920061 (80) [back to overview] | Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology |
| NCT01920061 (80) [back to overview] | Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation |
| NCT01920061 (80) [back to overview] | Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Triple Negative Breast Cancer - Arm B |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Transitional Cell Carcinoma - Arm B |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Prostate Cancer - Arm A |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Insulin - End of Treatment |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Ovarian Cancer - Arm B |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Non-Small Cell Lung Cancer - Arms A, B and C |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Head and Neck Cancer - Arm C |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Breast Cancer - Arms A and C |
| NCT01920061 (80) [back to overview] | Number of Participants With Vital Signs Data Meeting Pre-defined Criteria |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Insulin - Baseline |
| NCT01920061 (80) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (Treatment Related) - Arms A, B, C and B Expansion |
| NCT01920061 (80) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion |
| NCT01920061 (80) [back to overview] | Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Insulin - End of Treatment |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Insulin - End of Treatment |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B) |
| NCT01920061 (80) [back to overview] | Duration of Response - Arm B Expansion |
| NCT01920061 (80) [back to overview] | Clinical Benefit Response Rate - Arm B Expansion |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B) |
| NCT01920061 (80) [back to overview] | Progression Free Survival - Arm B Expansion |
| NCT01920061 (80) [back to overview] | Percentage of Participants With Objective Response - Arm C |
| NCT01920061 (80) [back to overview] | Percentage of Participants With Objective Response - Arm B Expansion |
| NCT01920061 (80) [back to overview] | Percentage of Participants With Objective Response - Arm B |
| NCT01920061 (80) [back to overview] | Percentage of Participants With Objective Response - Arm A |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B) |
| NCT01920061 (80) [back to overview] | Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
| NCT01920061 (80) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C) |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Glucose - Baseline |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Glucose - Baseline |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Glucose - Baseline |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Glucose - End of Treatment |
| NCT01920061 (80) [back to overview] | Mean Observed Score Values for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion |
| NCT01920061 (80) [back to overview] | Mean Change From Baseline for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C) |
| NCT01920061 (80) [back to overview] | Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B) |
| NCT01920061 (80) [back to overview] | Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C) |
| NCT01920061 (80) [back to overview] | Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A) |
| NCT01920061 (80) [back to overview] | Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C) |
| NCT01920061 (80) [back to overview] | Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C) |
| NCT01920061 (80) [back to overview] | Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
| NCT01920061 (80) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B) |
| NCT01920061 (80) [back to overview] | Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion) |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A) |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Glucose - End of Treatment |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Glucose - End of Treatment |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Insulin - Baseline |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment |
| NCT01920061 (80) [back to overview] | Mean Serum Biomarkers for Insulin - Baseline |
| NCT01920061 (80) [back to overview] | Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Docetaxel in Combination With PF-05212384 - Plasma Docetaxel (Arm A) |
| NCT01920061 (80) [back to overview] | Percentage of Participants With BRAF and KRAS Mutations in Population of Oesophageal Carcinoma - Arm C |
| NCT01920061 (80) [back to overview] | Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C) |
| NCT01932697 (9) [back to overview] | Change From Mean Baseline Score to Mean Score at 12 Months Post-RT in Swallow Function as Measured by the Pharyngeal Total Modified Barium Swallow Impairment Profile. |
| NCT01932697 (9) [back to overview] | Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (Version 4) |
| NCT01932697 (9) [back to overview] | 2-year Distant Metastasis-free Survival Rate |
| NCT01932697 (9) [back to overview] | Incidence of Grade 3 or Higher Mucositis Oral |
| NCT01932697 (9) [back to overview] | 2-year Loco-regional Tumor Control (LRC) Rate |
| NCT01932697 (9) [back to overview] | 2-year Overall Survival (OS) Rate |
| NCT01932697 (9) [back to overview] | 2-year Progression-free Survival (PFS) |
| NCT01932697 (9) [back to overview] | European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35) |
| NCT01932697 (9) [back to overview] | EuroQol Five-dimensional Instrument (EQ-5D-3L) |
| NCT01933932 (6) [back to overview] | Symptom Improvement Rate Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS) |
| NCT01933932 (6) [back to overview] | Duration of Response (DoR) |
| NCT01933932 (6) [back to overview] | Overall Survival (OS) |
| NCT01933932 (6) [back to overview] | Time to Symptom Progression Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS) |
| NCT01933932 (6) [back to overview] | Progression-Free Survival (PFS) |
| NCT01933932 (6) [back to overview] | Objective Response Rate (ORR) |
| NCT01940497 (11) [back to overview] | Percentage of Participants With Event (Local, Regional or Distant Recurrence, Contralateral Breast Cancer or Death) Using Mammography |
| NCT01940497 (11) [back to overview] | Percentage of Participants by Response to Patient Satisfaction Questionnaire (PSQ) |
| NCT01940497 (11) [back to overview] | Duration of Treatment With Trastuzumab |
| NCT01940497 (11) [back to overview] | Disease-Free Survival (DFS) Using Mammography |
| NCT01940497 (11) [back to overview] | Actual Dose of Trastuzumab Administered |
| NCT01940497 (11) [back to overview] | Percentage of Health Care Professionals (HCPs) by Response to Health Care Professional Questionnaire (HCPQ) |
| NCT01940497 (11) [back to overview] | Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) |
| NCT01940497 (11) [back to overview] | Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography |
| NCT01940497 (11) [back to overview] | Percentage of Participants Who Received Concomitant Medications |
| NCT01940497 (11) [back to overview] | Percentage of Participants Who Died |
| NCT01940497 (11) [back to overview] | Overall Survival (OS) |
| NCT01951157 (8) [back to overview] | Information on Quality of Life (QoL) |
| NCT01951157 (8) [back to overview] | Information on Quality of Life (QoL) |
| NCT01951157 (8) [back to overview] | Progression-free Survival Rate at Six Months (PFS6) |
| NCT01951157 (8) [back to overview] | Progression-free Survival Rate at Four Months (PFS4) |
| NCT01951157 (8) [back to overview] | Progression-free Survival |
| NCT01951157 (8) [back to overview] | Overall Survival (OS) |
| NCT01951157 (8) [back to overview] | Overall Response Rate |
| NCT01951157 (8) [back to overview] | Duration of Response |
| 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. |
| NCT01966471 (12) [back to overview] | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score |
| NCT01966471 (12) [back to overview] | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time |
| NCT01966471 (12) [back to overview] | Time to Clinically Meaningful Deterioration in the Global Health Status/ Quality of Life and Functional (Physical, Role, and Cognitive) Subscales of the QLQ-C30 From First HER2-Targeted Treatment |
| NCT01966471 (12) [back to overview] | Distant Recurrence-Free Interval (DRFI) |
| NCT01966471 (12) [back to overview] | Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation |
| NCT01966471 (12) [back to overview] | IDFS Plus Second Primary Non-Breast Cancer |
| NCT01966471 (12) [back to overview] | Disease-Free Survival (DFS) |
| NCT01966471 (12) [back to overview] | Overall Survival (OS) |
| NCT01966471 (12) [back to overview] | Invasive Disease-Free Survival (IDFS) in the Overall Population |
| NCT01966471 (12) [back to overview] | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score |
| NCT01966471 (12) [back to overview] | EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score |
| NCT01966471 (12) [back to overview] | Percentage of Participants With Adverse Events |
| NCT02003209 (5) [back to overview] | Percent of Patients With Pathological Complete Response (pCR) in the Breast and Post Therapy Lymph Nodes |
| 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] | 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 by Menopausal Status |
| NCT02003209 (5) [back to overview] | Median Percentage of Tumor-infiltrating Lymphocytes (sTILS) |
| NCT02005549 (3) [back to overview] | Percentage of Participants Undergoing Breast-Conserving Surgery |
| NCT02005549 (3) [back to overview] | Percentage of Participants With pCR, Clinical Complete Response (CR), or Clinical Partial Response (PR) |
| NCT02005549 (3) [back to overview] | Percentage of Participants With Pathological Complete Response (pCR) |
| NCT02008227 (37) [back to overview] | PFS as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP |
| NCT02008227 (37) [back to overview] | Progression-Free Survival (PFS) as Determined by Investigator Using RECIST v1.1: PP-ITT |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Pain in Arm or Shoulder |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Hemoptysis |
| NCT02008227 (37) [back to overview] | EORTC QLQ Core 30 (C30) Questionnaire Score: Single Items |
| NCT02008227 (37) [back to overview] | EORTC QLQ-C30 Questionnaire Score: Functional Subscales |
| NCT02008227 (37) [back to overview] | EORTC QLQ-C30 Questionnaire Score: GHS Scale |
| NCT02008227 (37) [back to overview] | EORTC QLQ-C30 Questionnaire Score: Symptom Subscale |
| NCT02008227 (37) [back to overview] | DOR as Determined by Investigator Using RECIST v1.1: SP ITT |
| NCT02008227 (37) [back to overview] | DOR as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP |
| NCT02008227 (37) [back to overview] | Duration of Response (DOR) as Determined by Investigator Using RECIST v1.1: PP-ITT |
| NCT02008227 (37) [back to overview] | Maximum Observed Serum Atezolizumab Concentration (Cmax) |
| NCT02008227 (37) [back to overview] | OS: SP-ITT |
| NCT02008227 (37) [back to overview] | OS: TC1/2/3 or IC1/2/3 Subgroup of PP |
| NCT02008227 (37) [back to overview] | OS: TC1/2/3 Or IC1/2/3 Subgroup of SP |
| NCT02008227 (37) [back to overview] | OS: TC2/3 or IC2/3 Subgroup of SP |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Pain in Chest |
| NCT02008227 (37) [back to overview] | Overall Survival (OS): PP-ITT |
| NCT02008227 (37) [back to overview] | Percentage of Participants Who Died: Tumor Cells (TC)1/2/3 or Tumor-Infiltrating Immune Cells (IC)1/2/3 Subgroup of PP |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Dyspnea |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Dysphagia |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Coughing |
| NCT02008227 (37) [back to overview] | Percentage of Participants Who Died: PP-ITT |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Pain in Other Parts |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Peripheral Neuropathy |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Sore Mouth |
| NCT02008227 (37) [back to overview] | Percentage of Participants With Objective Response as Determined Using RECIST v1.1: PP-ITT |
| NCT02008227 (37) [back to overview] | Minimum Observed Serum Atezolizumab Concentration (Cmin) |
| NCT02008227 (37) [back to overview] | Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms, Using the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ) Lung Cancer Supplemental Module 13 (LC13) |
| NCT02008227 (37) [back to overview] | EORTC QLQ-LC13 Questionnaire Score: Alopecia |
| NCT02008227 (37) [back to overview] | Percentage of Participants With Disease Progression (PD) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death: PP-ITT |
| NCT02008227 (37) [back to overview] | Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab |
| NCT02008227 (37) [back to overview] | Percentage of Participants With Objective Response as Determined Using RECIST v1.1: SP-ITT |
| NCT02008227 (37) [back to overview] | Percentage of Participants With Objective Response as Determined Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP |
| NCT02008227 (37) [back to overview] | Percentage of Participants With PD as Determined by Investigator Using RECIST v1.1 or Death: TC1/2/3 or IC1/2/3 Subgroup of PP |
| NCT02008227 (37) [back to overview] | PFS as Determined by Investigator Using RECIST v1.1: SP-ITT |
| NCT02008227 (37) [back to overview] | OS: TC3 or IC3 Subgroup of SP |
| NCT02019277 (14) [back to overview] | OS During Second-Line of Treatment |
| NCT02019277 (14) [back to overview] | Percentage of Participants Who Died Due to Any Cause |
| NCT02019277 (14) [back to overview] | Percentage of Participants Who Died During Receiving Second-Line of Treatment |
| NCT02019277 (14) [back to overview] | Percentage of Participants With AEs Leading to Premature Discontinuation of Investigational Medicinal Products (IMPs) |
| NCT02019277 (14) [back to overview] | Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
| NCT02019277 (14) [back to overview] | Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Below 50% |
| NCT02019277 (14) [back to overview] | Percentage of Participants With PD (Assessed According to RECIST Version 1.1) or Death Due to Any Cause |
| NCT02019277 (14) [back to overview] | Progression-free Survival (PFS) Assessed According to RECIST Version 1.1 |
| NCT02019277 (14) [back to overview] | Number of Participants Receiving Second-Line Treatment by Treatment Type |
| NCT02019277 (14) [back to overview] | Percentage of Participants With Adverse Events (AEs) and Serious AEs |
| NCT02019277 (14) [back to overview] | Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades |
| NCT02019277 (14) [back to overview] | Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA) |
| NCT02019277 (14) [back to overview] | Overall Survival (OS) |
| NCT02019277 (14) [back to overview] | Event-free Survival (EFS) Assessed According to RECIST Version 1.1 |
| NCT02027376 (9) [back to overview] | Time To Progression (TTP) |
| NCT02027376 (9) [back to overview] | Docetaxel Clearance on Cycle 1 and Cycle 2 (Pharmacokinetics (PK)) |
| NCT02027376 (9) [back to overview] | Changes in QT/QTc From Baseline and Cycle 3 ECG Values. |
| NCT02027376 (9) [back to overview] | The Number of Participants Who Experienced Adverse Events (AE) |
| NCT02027376 (9) [back to overview] | Recommended Phase II Dose (RP2D) of LDE225 (Sonidegib) in Combination With Docetaxel |
| NCT02027376 (9) [back to overview] | Objective Response Rate (ORR) |
| NCT02027376 (9) [back to overview] | Maximum Tolerated Dose (MTD) of LDE225 (Sonidegib) in Combination With Docetaxel |
| NCT02027376 (9) [back to overview] | LDE225 (Sonidegib) Trough Concentration (Pharmacokinetics (PK)) |
| NCT02027376 (9) [back to overview] | Incidence Rate of DLT Within the First Two Cycles of LDE225 (Sonidegib) in Combination With Docetaxel |
| NCT02105636 (4) [back to overview] | Overall Survival (OS) |
| NCT02105636 (4) [back to overview] | Investigator-Assessed Objective Response Rate (ORR) |
| NCT02105636 (4) [back to overview] | Investigator-Assessed Progression-Free Survival (PFS) |
| NCT02105636 (4) [back to overview] | Overall Survival (OS) - Extended Collection |
| NCT02117024 (6) [back to overview] | Time to Progression (TTP) |
| NCT02117024 (6) [back to overview] | Survival at 6 Months |
| NCT02117024 (6) [back to overview] | Overall Survival (OS) |
| NCT02117024 (6) [back to overview] | Survival at 12 Months |
| NCT02117024 (6) [back to overview] | Frequency of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events (TEAE) |
| NCT02117024 (6) [back to overview] | Progression-Free Survival (PFS) |
| 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] | 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] | 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: Blood to Plasma (B/P) Concentration Ratio for MLN4924 |
| NCT02122770 (17) [back to overview] | Part A: Plasma Clearance (CLp) for MLN4924 |
| NCT02122770 (17) [back to overview] | Part B: Percentage of Participants With Objective Response |
| NCT02122770 (17) [back to overview] | Part A: Volume of Distribution (Vz) for MLN4924 |
| NCT02122770 (17) [back to overview] | Part A: Terminal Phase Elimination Half-life (T1/2) for MLN4924 |
| NCT02124902 (1) [back to overview] | Pathological Complete Response (pCR) Rate |
| NCT02126969 (3) [back to overview] | Change in Quality of Life (QOL) of Patients Receiving Low Dose Fractionated Radiation Therapy With Chemotherapy. |
| NCT02126969 (3) [back to overview] | Primary Site Complete Response Rate |
| NCT02126969 (3) [back to overview] | 3-year Overall Survival |
| NCT02127372 (4) [back to overview] | Phase 1 - Maximum Tolerated Dose (MTD) of STI571 |
| NCT02127372 (4) [back to overview] | Phase 2: 1 Year Survival |
| NCT02127372 (4) [back to overview] | Phase II - Radiographic Response |
| NCT02127372 (4) [back to overview] | Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin |
| NCT02131064 (22) [back to overview] | Time to Clinically Meaningful Deterioration in GHS/QoL Score |
| NCT02131064 (22) [back to overview] | Cmax of Trastuzumab Emtansine and Total Trastuzumab |
| NCT02131064 (22) [back to overview] | Percentage of Participants With Total Pathological Complete Response (tpCR) Assessed Based on Tumor Samples |
| NCT02131064 (22) [back to overview] | Invasive Disease-free Survival (IDFS) |
| NCT02131064 (22) [back to overview] | Minimum Observed Serum Concentration (Cmin) of Trastuzumab |
| NCT02131064 (22) [back to overview] | Percentage of Participants With a Clinically Meaningful Deterioration in Function Subscales |
| 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] | Percentage of Participants With a Clinically Meaningful Increase in Symptom 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] | Event-Free Survival |
| NCT02131064 (22) [back to overview] | Overall Survival |
| NCT02131064 (22) [back to overview] | Percentage of Participants Who Received Breast-Conserving Surgery (BCS) |
| 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] | 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 |
| NCT02132949 (15) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Invasive Disease-Free Survival (iDFS) at 1 to 4 Years, Determined by the Investigator According to RECIST v1.1 |
| NCT02132949 (15) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1 to 5 Years |
| NCT02132949 (15) [back to overview] | Overview of the Number of Participants With at Least One Adverse Event During the Adjuvant Period |
| NCT02132949 (15) [back to overview] | Overview of the Number of Participants With at Least One Adverse Event During the Neoadjuvant Period |
| NCT02132949 (15) [back to overview] | Overview of the Number of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants Positive for Anti-Therapeutic Antibodies (ATAs) to Pertuzumab at Baseline and Anytime Post-Baseline |
| NCT02132949 (15) [back to overview] | Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Adjuvant Treatment Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Neoadjuvant Treatment Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Treatment-Free Follow-Up Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants With Clinical Response as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 During the Neoadjuvant Treatment Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Treatment-Free Follow-Up Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Adjuvant Treatment Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Neoadjuvant Treatment Period |
| NCT02132949 (15) [back to overview] | Percentage of Participants With Total Pathologic Complete Response (tpCR), Evaluated After Surgery |
| NCT02132949 (15) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1 to 5 Years, Determined by the Investigator According to RECIST v1.1 |
| NCT02144012 (14) [back to overview] | Progression-Free Survival (PFS) |
| NCT02144012 (14) [back to overview] | Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire |
| NCT02144012 (14) [back to overview] | Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF) |
| NCT02144012 (14) [back to overview] | Safety: Percentage of Participants With Grade 3 and 4 AEs |
| NCT02144012 (14) [back to overview] | Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption |
| NCT02144012 (14) [back to overview] | Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire |
| NCT02144012 (14) [back to overview] | Safety: Percentage of Participants With Adverse Events (AEs) |
| NCT02144012 (14) [back to overview] | Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction |
| NCT02144012 (14) [back to overview] | One-Year Survival Rate |
| NCT02144012 (14) [back to overview] | Objective Response Rate (ORR) |
| NCT02144012 (14) [back to overview] | Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine |
| NCT02144012 (14) [back to overview] | Percentage of Participants With Adverse Events Leading to Treatment Discontinuation |
| NCT02144012 (14) [back to overview] | Duration of Response (DOR) |
| NCT02144012 (14) [back to overview] | Overall Survival (OS) |
| NCT02145078 (2) [back to overview] | Overall Survival (OS) |
| NCT02145078 (2) [back to overview] | Progression-free Survival (PFS) |
| NCT02154490 (1) [back to overview] | Screen Success Rate |
| NCT02179671 (5) [back to overview] | Objective Response Rate (ORR) |
| NCT02179671 (5) [back to overview] | Overall Survival |
| NCT02179671 (5) [back to overview] | Progression-free Survival |
| NCT02179671 (5) [back to overview] | Confirmed Complete Response (CR) Rate |
| NCT02179671 (5) [back to overview] | Duration of Response |
| 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] | Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6. |
| 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] | Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6. |
| NCT02187744 (6) [back to overview] | Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6. |
| NCT02231164 (1) [back to overview] | Disease Control According to Response Evaluation Criteria in Solid Tumours (RECIST), Version 1.1 |
| NCT02252042 (17) [back to overview] | Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS |
| NCT02252042 (17) [back to overview] | Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants |
| NCT02252042 (17) [back to overview] | Updated Final OS for All Participants |
| NCT02252042 (17) [back to overview] | Time to Progression (TTP) Per RECIST 1.1 in All Participants |
| NCT02252042 (17) [back to overview] | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants |
| NCT02252042 (17) [back to overview] | PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
| NCT02252042 (17) [back to overview] | PFS Per Modified RECIST in All Participants |
| NCT02252042 (17) [back to overview] | PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
| NCT02252042 (17) [back to overview] | OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS) |
| NCT02252042 (17) [back to overview] | Duration of Response (DOR) Per RECIST 1.1 in All Participants |
| NCT02252042 (17) [back to overview] | TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
| NCT02252042 (17) [back to overview] | Initial Overall Survival (OS) for All Participants |
| NCT02252042 (17) [back to overview] | DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
| NCT02252042 (17) [back to overview] | Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants |
| NCT02252042 (17) [back to overview] | ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS |
| NCT02252042 (17) [back to overview] | Objective Response Rate (ORR) Per RECIST 1.1 in All Participants |
| NCT02252042 (17) [back to overview] | Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS |
| NCT02256436 (20) [back to overview] | Number of Participants Who Discontinued Study Treatment Due to an AE |
| NCT02256436 (20) [back to overview] | Number of Participants Who Experienced an Adverse Event (AE) |
| NCT02256436 (20) [back to overview] | Objective Response Rate (ORR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | ORR Per mRECIST - All Participants |
| NCT02256436 (20) [back to overview] | ORR Per mRECIST - Participants With PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | ORR Per mRECIST - Participants With Strongly PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | ORR Per RECIST 1.1 - All Participants |
| NCT02256436 (20) [back to overview] | ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | OS - Participants With PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | OS - Participants With Strongly PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | PFS Per Modified RECIST (mRECIST) - Participants With Strongly PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | PFS Per mRECIST - All Participants |
| NCT02256436 (20) [back to overview] | PFS Per mRECIST - Participants With PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | PFS Per RECIST 1.1 - Participants With Programmed Cell Death-Ligand (PD-L1) Positive Tumors |
| NCT02256436 (20) [back to overview] | PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants |
| NCT02256436 (20) [back to overview] | DOR Per RECIST 1.1 - All Participants |
| NCT02256436 (20) [back to overview] | DOR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | Duration of Response (DOR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors |
| NCT02256436 (20) [back to overview] | Overall Survival (OS) - All Participants |
| NCT02288247 (9) [back to overview] | Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS) |
| NCT02288247 (9) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) |
| NCT02288247 (9) [back to overview] | Time to Prostate-specific Antigen (PSA) Progression |
| NCT02288247 (9) [back to overview] | Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P) |
| NCT02288247 (9) [back to overview] | Prostate-specific Antigen (PSA) Response |
| NCT02288247 (9) [back to overview] | Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS) |
| NCT02288247 (9) [back to overview] | Objective Response Rate (ORR) |
| NCT02288247 (9) [back to overview] | Progression Free Survival (PFS) |
| NCT02288247 (9) [back to overview] | Time to First Skeletal-related Event (SRE) |
| NCT02300298 (7) [back to overview] | AUC0-infinity of Docetaxel |
| NCT02300298 (7) [back to overview] | Maximum Measured Concentration (Cmax) of Nintedanib |
| NCT02300298 (7) [back to overview] | Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity) |
| NCT02300298 (7) [back to overview] | Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 to Time of the Last Quantifiable Concentration (AUC0-tz) |
| NCT02300298 (7) [back to overview] | Number of Patients Experiencing Dose Limiting Toxicity (DLT) in Cycle 1 |
| NCT02300298 (7) [back to overview] | Cmax of Docetaxel |
| NCT02300298 (7) [back to overview] | AUC0-tz of Docetaxel |
| NCT02302807 (11) [back to overview] | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Physical Functioning Scale |
| NCT02302807 (11) [back to overview] | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Global Health Status Scale |
| NCT02302807 (11) [back to overview] | Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Fatigue Symptom Scale |
| NCT02302807 (11) [back to overview] | Unconfirmed Duration of Response (DOR) as Determined by the Investigator With Use of RECIST v1.1 |
| NCT02302807 (11) [back to overview] | Progression-free Survival (PFS) as Determined by the Investigator With Use of RECIST v1.1 |
| NCT02302807 (11) [back to overview] | Percentage of Participants With Post-Baseline Anti-therapeutic Antibodies (ATA) to Atezolizumab |
| NCT02302807 (11) [back to overview] | Percentage of Participants With Adverse Events (AEs) |
| NCT02302807 (11) [back to overview] | Overall Survival (OS) |
| NCT02302807 (11) [back to overview] | Maximum Observed Serum Atezolizumab Concentration (Cmax) |
| NCT02302807 (11) [back to overview] | Percentage of Participants With Unconfirmed Objective Response Rate (ORR) as Determined by the Investigator With Use of Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1) |
| NCT02302807 (11) [back to overview] | Minimum Observed Serum Atezolizumab Concentration (Cmin) |
| NCT02322281 (5) [back to overview] | Overall Survival (OS) |
| NCT02322281 (5) [back to overview] | Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS) |
| NCT02322281 (5) [back to overview] | Percentage of Participants With Confirmed Response |
| NCT02322281 (5) [back to overview] | Duration of Response (DOR) According to RECIST Version 1.1 as Determined by Investigator Assessment |
| NCT02322281 (5) [back to overview] | Plasma PK for Patients Treated With Rociletinib Based on Sparse Sampling |
| NCT02324543 (10) [back to overview] | Disease Control Rate (DCR) Using RECIST 1.1 Criteria |
| NCT02324543 (10) [back to overview] | Response Rate (RR) Using RECIST 1.1 Criteria |
| NCT02324543 (10) [back to overview] | Progression-free Survival (PFS) Using RECIST 1.1 Criteria |
| NCT02324543 (10) [back to overview] | Overall Survival (OS) Rate at 9 Months |
| NCT02324543 (10) [back to overview] | Overall Survival (OS) |
| NCT02324543 (10) [back to overview] | Maximum Tolerated Dose (MTD) of Gemcitabine |
| NCT02324543 (10) [back to overview] | Maximum Tolerated Dose (MTD) of Docetaxel |
| NCT02324543 (10) [back to overview] | Maximum Tolerated Dose (MTD) of Irinotecan |
| NCT02324543 (10) [back to overview] | Maximum Tolerated Dose (MTD) of Cisplatin |
| NCT02324543 (10) [back to overview] | Maximum Tolerated Dose (MTD) of Capecitabine |
| NCT02346370 (2) [back to overview] | Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel |
| NCT02346370 (2) [back to overview] | Number of Dose Limiting Toxicities (DLTs) |
| NCT02358473 (6) [back to overview] | Progression Free Survival by RECIST 1.1 |
| NCT02358473 (6) [back to overview] | Overall Survival |
| NCT02358473 (6) [back to overview] | Overall Response Rate |
| NCT02358473 (6) [back to overview] | Number of Subjects Reporting Serious Adverse Events |
| NCT02358473 (6) [back to overview] | Number of Subjects Reporting Adverse Events |
| NCT02358473 (6) [back to overview] | Number of Subjects Experiencing Dose-limiting Toxicity |
| NCT02358863 (1) [back to overview] | The Number of Patients With Tumor Size Reduction (Objective Response Rate) |
| NCT02387216 (6) [back to overview] | Objective Response Rate |
| NCT02387216 (6) [back to overview] | Number of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone |
| NCT02387216 (6) [back to overview] | Percentage of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone |
| NCT02387216 (6) [back to overview] | Time to Progression |
| NCT02387216 (6) [back to overview] | Progression Free Survival |
| NCT02387216 (6) [back to overview] | Overall Survival |
| NCT02393209 (9) [back to overview] | Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 1b |
| NCT02393209 (9) [back to overview] | Recommended Phase 2 Dose of TAK-117 in Phase 1b |
| NCT02393209 (9) [back to overview] | Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b |
| NCT02393209 (9) [back to overview] | Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b |
| NCT02393209 (9) [back to overview] | Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b |
| NCT02393209 (9) [back to overview] | Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1b |
| NCT02393209 (9) [back to overview] | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b |
| NCT02393209 (9) [back to overview] | TAK-117 Plasma Concentration in Phase 1b |
| NCT02393209 (9) [back to overview] | Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b |
| NCT02393248 (39) [back to overview] | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 2: Overall Response Rate (ORR) |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Tmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: CL/F Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: AUC0-24 Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States |
| NCT02393248 (39) [back to overview] | Emax Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2 |
| NCT02393248 (39) [back to overview] | Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2 |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Vz/F Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02393248 (39) [back to overview] | EC50 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2 |
| NCT02393248 (39) [back to overview] | Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE) |
| NCT02393248 (39) [back to overview] | Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Part 3: Number of Participants With Any TEAE |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Cmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States |
| NCT02393248 (39) [back to overview] | E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2 |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Cmin Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: t1/2 Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1 |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 3: ORR |
| NCT02393248 (39) [back to overview] | Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State) |
| NCT02393248 (39) [back to overview] | Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State) |
| NCT02395172 (14) [back to overview] | Number of Participants With Positive Anti-Drug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) for Avelumab |
| NCT02395172 (14) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity |
| NCT02395172 (14) [back to overview] | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT) |
| NCT02395172 (14) [back to overview] | Overall Survival (OS) Time in Full Analysis Set Population |
| NCT02395172 (14) [back to overview] | Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS) |
| NCT02395172 (14) [back to overview] | Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population |
| NCT02395172 (14) [back to overview] | Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population |
| NCT02395172 (14) [back to overview] | Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT) |
| NCT02395172 (14) [back to overview] | Progression-Free Survival (PFS) Time in Full Analysis Set Population |
| NCT02395172 (14) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Drug Related Treatment Emergent Adverse Events and Treatment Emergent Adverse Events Leading to Death |
| NCT02395172 (14) [back to overview] | Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population |
| NCT02395172 (14) [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) |
| NCT02395172 (14) [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) |
| NCT02395172 (14) [back to overview] | Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score vs. Worst Post-baseline Score |
| NCT02401542 (1) [back to overview] | Primary Efficacy Outcome: Progression Free Survival (PFS) |
| 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] | Disease Free Survival (DFS) |
| 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 |
| NCT02426125 (11) [back to overview] | Percentage of Participants With Disease Control Rate (DCR) |
| NCT02426125 (11) [back to overview] | Progression Free Survival (PFS) |
| NCT02426125 (11) [back to overview] | Percentage of Participants With an Objective Response Rate (ORR) |
| NCT02426125 (11) [back to overview] | Overall Survival (OS) |
| NCT02426125 (11) [back to overview] | PK: Minimum Concentration (Cmin) of Ramucirumab |
| NCT02426125 (11) [back to overview] | Number of Participants With Anti-Ramucirumab Antibodies |
| NCT02426125 (11) [back to overview] | Duration of Response (DoR) |
| NCT02426125 (11) [back to overview] | Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale |
| NCT02426125 (11) [back to overview] | Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab |
| NCT02426125 (11) [back to overview] | Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS) |
| NCT02426125 (11) [back to overview] | Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Non-Serious Adverse Events by Event Outcome |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE) |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab |
| NCT02445586 (35) [back to overview] | Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant |
| NCT02445586 (35) [back to overview] | Median Duration of Overall Survival |
| NCT02445586 (35) [back to overview] | Median Duration of Progression-Free Survival |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03 |
| NCT02445586 (35) [back to overview] | Number of Participants With Congestive Heart Failure |
| NCT02445586 (35) [back to overview] | Number of Participants With Hematological Abnormalities Reported as Serious Adverse Events |
| NCT02445586 (35) [back to overview] | Number of Participants With Non-Serious Adverse Events Related to Trastuzumab |
| NCT02445586 (35) [back to overview] | Number of Participants With Serum Chemistry Abnormalities Reported as Serious Adverse Events |
| NCT02445586 (35) [back to overview] | Number of Participants With Coagulation Abnormalities Reported as Serious Adverse Events |
| NCT02445586 (35) [back to overview] | Number of Participants With Non-Serious Adverse Events Related to Docetaxel |
| NCT02445586 (35) [back to overview] | Number of Participants With Adverse Events Leading to Treatment Discontinuation |
| NCT02445586 (35) [back to overview] | Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time |
| NCT02445586 (35) [back to overview] | Number of Participants by Best Overall Response |
| NCT02445586 (35) [back to overview] | Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death |
| NCT02445586 (35) [back to overview] | Number of Participants Who Died or Were Censored for Overall Survival Analysis |
| NCT02445586 (35) [back to overview] | Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant |
| NCT02445586 (35) [back to overview] | Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events |
| NCT02445586 (35) [back to overview] | Number of Participants With Serious Adverse Events Related to Trastuzumab |
| NCT02445586 (35) [back to overview] | Number of Participants With Serious Adverse Events Related to Pertuzumab |
| NCT02445586 (35) [back to overview] | Number of Participants With Serious Adverse Events Related to Docetaxel |
| NCT02445586 (35) [back to overview] | Number of Participants With Non-Serious Adverse Events Related to Pertuzumab |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab |
| NCT02445586 (35) [back to overview] | Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events |
| NCT02445586 (35) [back to overview] | Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis |
| NCT02445586 (35) [back to overview] | Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events |
| NCT02445586 (35) [back to overview] | Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time |
| NCT02445586 (35) [back to overview] | Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months |
| NCT02445586 (35) [back to overview] | Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months |
| NCT02445586 (35) [back to overview] | Overall Response Rate |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03) |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Serious Adverse Events by Event Outcome |
| NCT02445586 (35) [back to overview] | Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug |
| NCT02450539 (10) [back to overview] | Time to Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status of >/=2 |
| NCT02450539 (10) [back to overview] | Pharmacokinetics (PK): Clearance of Abemaciclib |
| NCT02450539 (10) [back to overview] | Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire EQ VAS Overall Self-rated Health Score |
| NCT02450539 (10) [back to overview] | Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire Index Value |
| NCT02450539 (10) [back to overview] | Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR): Disease Control Rate (DCR) |
| NCT02450539 (10) [back to overview] | Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR]) |
| NCT02450539 (10) [back to overview] | Change From Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Scores |
| NCT02450539 (10) [back to overview] | Progression Free Survival (PFS) |
| NCT02450539 (10) [back to overview] | PK: Volume of Distribution of Abemaciclib |
| NCT02450539 (10) [back to overview] | Overall Survival (OS) |
| 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 |
| NCT02485834 (5) [back to overview] | Number of Participants Who Reported Grade 3 or Higher Adverse Events |
| NCT02485834 (5) [back to overview] | Number of Patients Achieved R0 Resection During Surgery |
| NCT02485834 (5) [back to overview] | Overall Survival |
| NCT02485834 (5) [back to overview] | Progression-free Survival |
| NCT02485834 (5) [back to overview] | Number of Patients Had Pathologic Complete Response |
| NCT02490475 (17) [back to overview] | CL for Docetaxel Alone and in Combination With Pertuzumab |
| NCT02490475 (17) [back to overview] | Vss for Docetaxel Alone and in Combination With Pertuzumab |
| NCT02490475 (17) [back to overview] | Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel |
| NCT02490475 (17) [back to overview] | Tmax for Docetaxel Alone and in Combination With Pertuzumab |
| NCT02490475 (17) [back to overview] | t1/2 for Docetaxel Alone and in Combination With Pertuzumab |
| NCT02490475 (17) [back to overview] | Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel |
| NCT02490475 (17) [back to overview] | Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint |
| NCT02490475 (17) [back to overview] | Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria |
| NCT02490475 (17) [back to overview] | Mean Residence Time (MRT) of Pertuzumab |
| NCT02490475 (17) [back to overview] | Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel |
| NCT02490475 (17) [back to overview] | Cmax for Docetaxel Alone and in Combination With Pertuzumab |
| NCT02490475 (17) [back to overview] | Clearance (Cl) of Pertuzimab in Combination With Docetaxel |
| NCT02490475 (17) [back to overview] | AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab |
| NCT02490475 (17) [back to overview] | AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel |
| NCT02490475 (17) [back to overview] | Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel |
| NCT02490475 (17) [back to overview] | Number of Participants With DLTs |
| NCT02490475 (17) [back to overview] | Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI) |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Pathologic Response |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Prostate-specific Antigen (PSA) Levels |
| NCT02494713 (13) [back to overview] | Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI) |
| NCT02494713 (13) [back to overview] | Safety of Drug Regimen as Measured by Number of Adverse Events |
| NCT02494713 (13) [back to overview] | Surgical Morbidity as Measured by Number of Adverse Events |
| NCT02494921 (13) [back to overview] | Percentage of Participants With Radiographic Progression-free Survival at 6 Months (Phase 1b/2 RP2D) |
| NCT02494921 (13) [back to overview] | Prostate-Specific Antigen (PSA) Response Rate (Phase 1b/2 RP2D) |
| NCT02494921 (13) [back to overview] | Mean Maximum Serum Concentration of Ribociclib (Cmax) (Phase 1b) |
| NCT02494921 (13) [back to overview] | RP2D of Docetaxel (Phase 1b) |
| NCT02494921 (13) [back to overview] | Median PSA Progression-Free Survival (Phase 1b/2 RP2D) |
| NCT02494921 (13) [back to overview] | Median Duration of Response (Phase1b/2 RP2D) |
| NCT02494921 (13) [back to overview] | Mean Area Under Curve (AUC) 0-24 Hour (Phase 1b) |
| NCT02494921 (13) [back to overview] | Mean Area Under Curve (AUC) 0-24 Hour (Phase 1b) |
| NCT02494921 (13) [back to overview] | Maximally Tolerated Dose (MTD) (Phase 1b) |
| NCT02494921 (13) [back to overview] | Mean Maximum Serum Concentration of Ribociclib (Cmax) (Phase 1b) |
| NCT02494921 (13) [back to overview] | Median Radiographic Progression-free Survival (Phase1b/2 RP2D) |
| NCT02494921 (13) [back to overview] | Number of Participants With Treatment-Related Adverse Events |
| NCT02494921 (13) [back to overview] | Objective Response Rate (ORR) (Phase1b/2 RP2D) |
| NCT02502864 (2) [back to overview] | Incidence of Grade 3 and 4 Neutropenia and Febrile Neutropenia |
| NCT02502864 (2) [back to overview] | Rate of Achieving Targeted Area Under the Curve (AUC) |
| NCT02511132 (3) [back to overview] | Number of Participants With Adverse Events Determined by Laboratory Assessments and Physical Examinations |
| NCT02511132 (3) [back to overview] | Overall Survival |
| NCT02511132 (3) [back to overview] | Progression Free Survival |
| NCT02516670 (7) [back to overview] | Number of Participates With a Decline in Prostate-specific Antigen From Their Baseline Measurement |
| NCT02516670 (7) [back to overview] | Radiographic Progression Free Survival (rPFS) |
| NCT02516670 (7) [back to overview] | Number of Participants With Adverse Events |
| NCT02516670 (7) [back to overview] | Number of Serious Adverse Events |
| NCT02516670 (7) [back to overview] | Average Number of Times Docetaxel Had Dose Reductions |
| NCT02516670 (7) [back to overview] | Number of Participates Experiencing Serious Adverse Events (SAE) |
| NCT02516670 (7) [back to overview] | Change in Quality of Life (QoL) as Measured by the FACT-P Questionnaire |
| NCT02524275 (3) [back to overview] | Survival |
| NCT02524275 (3) [back to overview] | Overall Response Rate of Complete or Partial Response |
| NCT02524275 (3) [back to overview] | Progression-free Survival |
| NCT02547987 (1) [back to overview] | Pathologic Complete Response |
| NCT02551055 (8) [back to overview] | Number of Participants With at Least 1 ≥ Grade 3 TEAE in Part 1 |
| NCT02551055 (8) [back to overview] | Number of Participants With at Least 1 TEAE and Serious TEAE in Part 1 and 2 |
| NCT02551055 (8) [back to overview] | Number of Participants With at Least 1 Dose Modification Due to AE in Part 1 |
| NCT02551055 (8) [back to overview] | Number of Participants Who Experienced Cycle 1 Dose Limiting Toxicity (DLT) in Part 1 |
| NCT02551055 (8) [back to overview] | Number of Participants With at Least 1 Treatment-Emergent Adverse Event (TEAE) in Part 1 |
| NCT02551055 (8) [back to overview] | Plasma Concentration of MLN1117-1003 |
| NCT02551055 (8) [back to overview] | Number of Participants With at Least 1 Treatment-Emergent Serious Adverse Event (SAE) in Part 1 |
| NCT02551055 (8) [back to overview] | Number of Participants With Dose Delays, Dose Reductions, and Dose Interruptions Due To AE in Part 1 and 2 |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by PSA Level |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by PSA Level |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by PSA Level |
| NCT02560051 (17) [back to overview] | Quality of Life Measure by FACT-P Scale |
| NCT02560051 (17) [back to overview] | Quality of Life Measure by FACT-P Scale |
| NCT02560051 (17) [back to overview] | Quality of Life Measure by FACT-P Scale |
| NCT02560051 (17) [back to overview] | Quality of Life Measure by FACT-P Scale |
| NCT02560051 (17) [back to overview] | Safety of Drug Regimen as Measured by Number of Adverse Events |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by PSA Level |
| NCT02560051 (17) [back to overview] | Quality of Life Measure by FACT-P Scale |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by Number Who Progressed |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by Number Who PSA Progressed |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by Number of Participants With Pathology/Biopsy Positive for Disease |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by PSA Level |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by PSA Level |
| NCT02560051 (17) [back to overview] | Quality of Life Measure by FACT-P Scale |
| NCT02560051 (17) [back to overview] | Efficacy as Measured by PSA Level |
| NCT02564263 (11) [back to overview] | Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) |
| NCT02564263 (11) [back to overview] | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants |
| NCT02564263 (11) [back to overview] | Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus |
| NCT02564263 (11) [back to overview] | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants |
| NCT02564263 (11) [back to overview] | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus |
| NCT02564263 (11) [back to overview] | Overall Survival (OS) in All Participants |
| NCT02564263 (11) [back to overview] | Number of Participants Experiencing an Adverse Event (AE) |
| NCT02564263 (11) [back to overview] | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) |
| NCT02564263 (11) [back to overview] | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus |
| NCT02564263 (11) [back to overview] | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) |
| NCT02564263 (11) [back to overview] | Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE) |
| 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) |
| 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) |
| NCT02569242 (3) [back to overview] | Progression-free Survival |
| NCT02569242 (3) [back to overview] | Overall Survival |
| NCT02569242 (3) [back to overview] | Duration of Response |
| NCT02574078 (7) [back to overview] | Duration of Response (DOR), Groups A-D Only |
| NCT02574078 (7) [back to overview] | Objective Response Rate (ORR), Groups A-E |
| 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), Groups A-C Only |
| NCT02574078 (7) [back to overview] | Overall Survival (OS), Group D Only |
| NCT02574078 (7) [back to overview] | Progression-Free Survival (PFS), Group E Only |
| NCT02574078 (7) [back to overview] | Progression-Free Survival (PFS), Groups A-D Only |
| NCT02574598 (1) [back to overview] | Overall Response Rate |
| NCT02586025 (16) [back to overview] | Percentage of Participants With Breast Pathologic Complete Response (bpCR), Defined as ypT0/is According to the AJCC Staging System as Assessed by the IRC |
| NCT02586025 (16) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Disease-Free Survival (DFS) at 1, 3, and 5 Years |
| NCT02586025 (16) [back to overview] | Percentage of Participants Who Experienced a Primary Cardiac Event |
| NCT02586025 (16) [back to overview] | Change From Baseline in LVEF Over Time |
| NCT02586025 (16) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1, 3, and 5 Years |
| NCT02586025 (16) [back to overview] | Percentage of Participants With tpCR as Assessed by the Local Pathologist |
| NCT02586025 (16) [back to overview] | Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC) |
| NCT02586025 (16) [back to overview] | Maximum Change From Baseline in LVEF |
| NCT02586025 (16) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1, 3, and 5 Years |
| NCT02586025 (16) [back to overview] | Percentage of Participants With an Objective Response (CR or PR) During Cycles 1-4, According to RECIST Version 1.1 |
| NCT02586025 (16) [back to overview] | Percentage of Participants With at Least One Adverse Event (AE) During the Neoadjuvant Treatment Period |
| NCT02586025 (16) [back to overview] | Percentage of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period |
| NCT02586025 (16) [back to overview] | Percentage of Participants Who Experienced a Secondary Cardiac Event |
| NCT02586025 (16) [back to overview] | Percentage of Participants With at Least One AE During the Adjuvant Treatment Period |
| NCT02586025 (16) [back to overview] | Percentage of Participants With bpCR as Assessed by the Local Pathologist |
| NCT02586025 (16) [back to overview] | Percentage of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 |
| NCT02599324 (19) [back to overview] | Phase 1b/2 RP2D: DCR in Cohorts 1 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b: ORR in Cohorts 1 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b/2 RP2D: ORR in Cohorts 1 and 2 |
| NCT02599324 (19) [back to overview] | Phase 1b: Terminal Elimination Rate Constant (λz) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b: Area Under the Concentration-Time Curve From Time 0 to Hour 24 (AUC0-24h) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b: Apparent Total Clearance at Steady-State (CLss/F) for Ibrutinib in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b/2 RP2D: PFS in Cohorts 3 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b/2 RP2D: Progression-Free Survival (PFS) as Assessed by Investigator in Cohorts 1 and 2 |
| NCT02599324 (19) [back to overview] | Phase 1b/2 RP2D: Overall Response Rate (ORR) as Assessed by Investigator in Cohorts 3 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b/2 RP2D: Overall Survival (OS) in Cohorts 1 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b/2 RP2D: Duration of Response (DOR) in Cohorts 1 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b: Disease Control Rate (DCR) in Cohorts 1 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cohorts 1 to 6 |
| NCT02599324 (19) [back to overview] | Phase 1b: Time to Cmax (Tmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b: Time of Last Observed Concentration (Tlast) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b: Terminal Elimination Rate Constant (λz) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b: Terminal Elimination Half-Life (t1/2term) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b: Observed Maximum Concentration (Cmax) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02599324 (19) [back to overview] | Phase 1b: Area Under the Concentration-Time Curve to Last Observed Time Point (AUClast) for Ibrutinib and Its Metabolite PCI-45227 in Cohorts 1 to 4 |
| NCT02604342 (27) [back to overview] | TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population |
| NCT02604342 (27) [back to overview] | TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population |
| NCT02604342 (27) [back to overview] | Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC |
| NCT02604342 (27) [back to overview] | Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator |
| NCT02604342 (27) [back to overview] | Plasma Concentration of Alectinib Metabolite |
| NCT02604342 (27) [back to overview] | Plasma Concentration of Alectinib |
| NCT02604342 (27) [back to overview] | PFS Using RECIST Version 1.1 as Assessed by IRC |
| NCT02604342 (27) [back to overview] | Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC |
| NCT02604342 (27) [back to overview] | Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC |
| NCT02604342 (27) [back to overview] | Percentage of Participants With CNS Objective Response Rate (ORR) With Measurable CNS Metastases at Baseline Using RECIST Version 1.1 as Assessed By IRC |
| NCT02604342 (27) [back to overview] | Percentage of Participants With Adverse Events (AEs) |
| NCT02604342 (27) [back to overview] | Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC |
| NCT02604342 (27) [back to overview] | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time |
| NCT02604342 (27) [back to overview] | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population |
| NCT02604342 (27) [back to overview] | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time |
| NCT02604342 (27) [back to overview] | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population |
| NCT02604342 (27) [back to overview] | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population |
| NCT02604342 (27) [back to overview] | Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population |
| NCT02604342 (27) [back to overview] | Overall Survival (OS) |
| NCT02604342 (27) [back to overview] | PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC |
| NCT02604342 (27) [back to overview] | Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC |
| NCT02604342 (27) [back to overview] | Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC |
| NCT02604342 (27) [back to overview] | Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC |
| NCT02604342 (27) [back to overview] | Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time |
| NCT02604342 (27) [back to overview] | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time |
| NCT02604342 (27) [back to overview] | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time |
| NCT02604342 (27) [back to overview] | Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time |
| NCT02611960 (10) [back to overview] | Percentage of Participants Who Discontinue Study Treatment Due to an AE |
| NCT02611960 (10) [back to overview] | Duration of Response (DOR) Per RECIST 1.1 |
| NCT02611960 (10) [back to overview] | Percentage of Participants Who Experience One or More Adverse Events (AEs) |
| NCT02611960 (10) [back to overview] | Percentage of Participants Surviving (OS Rate) at 24 Months |
| NCT02611960 (10) [back to overview] | Percentage of Participants With PFS (PFS Rate) at 12 Months |
| NCT02611960 (10) [back to overview] | Percentage of Participants With PFS (PFS Rate) at 6 Months |
| NCT02611960 (10) [back to overview] | Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
| NCT02611960 (10) [back to overview] | Objective Response Rate (ORR) Per RECIST 1.1 |
| NCT02611960 (10) [back to overview] | Overall Survival (OS) |
| NCT02611960 (10) [back to overview] | Percentage of Participants Surviving (OS Rate) at 12 Months |
| NCT02613507 (6) [back to overview] | Median Overall Survival |
| NCT02613507 (6) [back to overview] | Overall Survival Rate |
| NCT02613507 (6) [back to overview] | Overall Survival in Subpopulations |
| NCT02613507 (6) [back to overview] | Median Progression Free Survival (PFS) |
| NCT02613507 (6) [back to overview] | Progression Free Survival Rate |
| NCT02613507 (6) [back to overview] | Objective Response Rate |
| NCT02642042 (10) [back to overview] | Progression Free Survival in Participants With G12C KRAS Mutation |
| NCT02642042 (10) [back to overview] | Progression Free Survival in All KRAS Mutant Participants |
| NCT02642042 (10) [back to overview] | Overall Survival in Participants With Non-G12C KRAS Mutation |
| NCT02642042 (10) [back to overview] | Overall Survival in All KRAS Mutants |
| NCT02642042 (10) [back to overview] | Overall Survival in Participants With G12C KRAS Mutation |
| NCT02642042 (10) [back to overview] | Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT02642042 (10) [back to overview] | Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With Non-G12C KRAS Mutation |
| NCT02642042 (10) [back to overview] | Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With G12C KRAS Mutation |
| NCT02642042 (10) [back to overview] | Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in All KRAS Mutant Participants |
| NCT02642042 (10) [back to overview] | Progression Free Survival in Participants With Non-G12C KRAS Mutation |
| NCT02643420 (9) [back to overview] | Number of Participants With Febrile Neutropenia (FN) in Cycle 1 |
| NCT02643420 (9) [back to overview] | Number of Participants With Neutropenic Complications in Cycle 1 |
| NCT02643420 (9) [back to overview] | Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 |
| NCT02643420 (9) [back to overview] | Duration of Severe Neutropenia in Cycle 2, 3 and 4 |
| NCT02643420 (9) [back to overview] | Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1 |
| NCT02643420 (9) [back to overview] | Duration of Severe Neutropenia (DSN) in Cycle 1 |
| NCT02643420 (9) [back to overview] | Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4 |
| NCT02643420 (9) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
| NCT02643420 (9) [back to overview] | Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4 |
| NCT02649855 (6) [back to overview] | Antigen Spreading (i.e., a Broader Immune Response) With Greater Associated Response Score Compared to Docetaxel Alone After 19 Weeks |
| NCT02649855 (6) [back to overview] | Number of Participants With T-cell Response to Prostate-specific Antigen (PSA) |
| NCT02649855 (6) [back to overview] | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0) |
| NCT02649855 (6) [back to overview] | Number of Participants With T-cell Response to Prostate-specific Antigen (PSA) |
| NCT02649855 (6) [back to overview] | Antigen Specific T-cell Immune Composite Response Scores Between All Arms at 39 Weeks and 1 Year |
| NCT02649855 (6) [back to overview] | Antigen Specific T-cell Immune Composite Response Scores Between All Arms at 39 Weeks and 1 Year |
| NCT02659020 (18) [back to overview] | Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD) |
| NCT02659020 (18) [back to overview] | Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab |
| NCT02659020 (18) [back to overview] | Phase 1b/2: Population PK: Clearance of Olaratumab |
| NCT02659020 (18) [back to overview] | Phase 1b/2: PK: Cmax of Gemcitabine |
| NCT02659020 (18) [back to overview] | Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel |
| NCT02659020 (18) [back to overview] | Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT) |
| NCT02659020 (18) [back to overview] | "Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) Worst Pain Score" |
| NCT02659020 (18) [back to overview] | Phase 1b/2: PK: Cmax of Docetaxel |
| NCT02659020 (18) [back to overview] | Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales. |
| NCT02659020 (18) [back to overview] | Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L) |
| NCT02659020 (18) [back to overview] | Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab |
| NCT02659020 (18) [back to overview] | Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab |
| NCT02659020 (18) [back to overview] | Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab |
| NCT02659020 (18) [back to overview] | Phase 2: Progression Free Survival (PFS) |
| NCT02659020 (18) [back to overview] | Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR]) |
| NCT02659020 (18) [back to overview] | Phase 2: Overall Survival (OS) (Olaratumab-Naive) |
| NCT02659020 (18) [back to overview] | Phase 2: Overall Survival (Olaratumab Pre-Treated) |
| NCT02659020 (18) [back to overview] | Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies |
| NCT02668393 (2) [back to overview] | Number of Participants With Dose-limiting Toxicity (DLT) During the First Treatment Cycle |
| NCT02668393 (2) [back to overview] | Maximum Tolerated Dose (MTD) of Nintedanib Administered in Combination With Docetaxel |
| NCT02685267 (3) [back to overview] | PSA Response in the Standard Treatment Arm and Experimental Treatment Arm |
| NCT02685267 (3) [back to overview] | Progression-free Survival (Radiographic or Per PCWG2 Criteria) |
| NCT02685267 (3) [back to overview] | Overall Survival |
| NCT02716974 (3) [back to overview] | Time to Prostate-specific Antigen Recurrence |
| NCT02716974 (3) [back to overview] | Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities |
| NCT02716974 (3) [back to overview] | Efficacy as Assessed by 2-year PSA Progression-free Survival Rate |
| NCT02718820 (4) [back to overview] | Overall Response Rate |
| NCT02718820 (4) [back to overview] | Median Overall Survival (OS) |
| NCT02718820 (4) [back to overview] | Median Progression Free Survival (PFS) |
| NCT02718820 (4) [back to overview] | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 |
| NCT02748213 (6) [back to overview] | Progression-Free Survival (PFS) According to RECIST |
| NCT02748213 (6) [back to overview] | Overall Survival (OS) |
| NCT02748213 (6) [back to overview] | Percentage of Participants With Death or Disease Progression According to RECIST |
| NCT02748213 (6) [back to overview] | Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) |
| NCT02748213 (6) [back to overview] | Duration of Response (DOR) According to RECIST |
| NCT02748213 (6) [back to overview] | Percentage of Participants Who Died |
| NCT02766335 (10) [back to overview] | Investigator-assessed Progression-free Survival |
| NCT02766335 (10) [back to overview] | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT02766335 (10) [back to overview] | Overall Survival |
| NCT02766335 (10) [back to overview] | Response Rate |
| NCT02766335 (10) [back to overview] | Overall Survival in PD-L1 Positive MEDI4736-treated Participants |
| NCT02766335 (10) [back to overview] | Overall Survival in MEDI4736-treated Participants |
| NCT02766335 (10) [back to overview] | Overall Response Rate Among PD-L1 Positive Participants Treated With MEDI4736 |
| NCT02766335 (10) [back to overview] | Response Rate in MEDI4736-treated Participants |
| NCT02766335 (10) [back to overview] | Investigator-assessed Progression-free Survival in Participants Treated With MEDI4736 |
| NCT02766335 (10) [back to overview] | Investigator-assessed Progression-free Survival in PD-L1 Positive Participants Treated With MEDI4736 |
| NCT02785939 (5) [back to overview] | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT02785939 (5) [back to overview] | Duration of Response Among Participants Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1 |
| NCT02785939 (5) [back to overview] | Overall Survival With Investigational Therapy |
| NCT02785939 (5) [back to overview] | Progression-free Survival With Palbociclib. |
| NCT02785939 (5) [back to overview] | Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial) |
| NCT02799602 (16) [back to overview] | Time to Initiation of Subsequent Antineoplastic Therapy - Month |
| NCT02799602 (16) [back to overview] | Time to Worsening of Disease-Related Physical Symptoms - Month |
| NCT02799602 (16) [back to overview] | OS From Date of Randomization Until Death From Any Cause - Number of Events |
| NCT02799602 (16) [back to overview] | Time to Pain Progression - Month |
| NCT02799602 (16) [back to overview] | Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events |
| NCT02799602 (16) [back to overview] | Time to Initiation of Opioid Use for ≥7 Consecutive Days - Number of Events |
| NCT02799602 (16) [back to overview] | Symptomatic Skeletal Event Free Survival (SSE-FS) - Month |
| NCT02799602 (16) [back to overview] | Time to First Symptomatic Skeletal Event (SSE) - Number of Events |
| NCT02799602 (16) [back to overview] | Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events |
| NCT02799602 (16) [back to overview] | Time to Worsening of Disease-Related Physical Symptoms - Number of Events |
| NCT02799602 (16) [back to overview] | Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events |
| NCT02799602 (16) [back to overview] | OS From Date of Randomization Until Death From Any Cause - Months |
| NCT02799602 (16) [back to overview] | Time to First Symptomatic Skeletal Event (SSE) - Month |
| NCT02799602 (16) [back to overview] | Time to Castration-Resistant Prostate Cancer (CRPC) - Month |
| NCT02799602 (16) [back to overview] | Time to Initiation of Opioid Use for ≥7 Consecutive Days - Month |
| NCT02799602 (16) [back to overview] | Time to Pain Progression - Number of Events |
| NCT02834403 (7) [back to overview] | Recommended Phase 2 Dose (RP2D) of the L-NMMA and Docetaxel Combination |
| NCT02834403 (7) [back to overview] | Asses the Maximum Tolerated Dose (MTD) of L-NMMA When Combined With Docetaxel/Amlodipine in the Treatment of Refractory Locally Advanced or Metastatic TNBC Patients, Based on the Number of Dose Limiting Toxicities (DLTs) Per Dose Level. |
| NCT02834403 (7) [back to overview] | Dose Limiting Toxicities (DLTs) and Other Adverse Events |
| NCT02834403 (7) [back to overview] | Recommended Phase 2 Dose (RP2D) of the L-NMMA and Docetaxel Combination |
| NCT02834403 (7) [back to overview] | Clinical Benefit Rate |
| NCT02834403 (7) [back to overview] | Time to Maximum Plasma Concentration of L-NMMA and Docetaxel |
| NCT02834403 (7) [back to overview] | Asses the Maximum Tolerated Dose (MTD) of Docetaxel When Combined With L-NMMA/Amlodipine in the Treatment of Refractory Locally Advanced or Metastatic TNBC Patients, Based on the Number of Dose Limiting Toxicities (DLTs) Per Dose Level. |
| NCT02864394 (13) [back to overview] | Number of Participants Who Experienced an AE That Was Experienced by ≥10% of Participants in Either Arm |
| NCT02864394 (13) [back to overview] | Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors |
| NCT02864394 (13) [back to overview] | ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) |
| NCT02864394 (13) [back to overview] | OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) |
| NCT02864394 (13) [back to overview] | PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) |
| NCT02864394 (13) [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 PD-L1 Positive (TPS ≥50%) Tumors |
| NCT02864394 (13) [back to overview] | Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors |
| NCT02864394 (13) [back to overview] | DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) |
| NCT02864394 (13) [back to overview] | Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors |
| NCT02864394 (13) [back to overview] | Number of Participants Who Discontinued Study Treatment Due to an AE |
| NCT02864394 (13) [back to overview] | Number of Participants Who Experienced a Grade 3-5 AE |
| NCT02864394 (13) [back to overview] | Number of Participants Who Experienced an Adverse Event (AE) |
| NCT02864394 (13) [back to overview] | Number of Participants Who Experienced an Adverse Event of Special Interest (AEOSI) |
| NCT02896855 (13) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1 |
| NCT02896855 (13) [back to overview] | Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1 |
| NCT02896855 (13) [back to overview] | Number of Participants With at Least One Grade ≥3 Adverse Event |
| NCT02896855 (13) [back to overview] | Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan |
| NCT02896855 (13) [back to overview] | Overall Survival |
| NCT02896855 (13) [back to overview] | Baseline LVEF and Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study |
| NCT02896855 (13) [back to overview] | Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years |
| NCT02896855 (13) [back to overview] | Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1 |
| NCT02896855 (13) [back to overview] | Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment |
| NCT02896855 (13) [back to overview] | Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
| NCT02896855 (13) [back to overview] | Number of Participants With at Least One Adverse Event |
| NCT02896855 (13) [back to overview] | Number of Participants With an Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan |
| NCT02896855 (13) [back to overview] | Number of Participants by the LVEF Abnormality Status Categories Over Time, as Determined by the Change From Baseline in LVEF Using ECHO or MUGA Scans |
| NCT02915744 (11) [back to overview] | Progression-Free Survival (Overall) |
| NCT02915744 (11) [back to overview] | Compare Health-Related Quality of Life (HRQoL) Using the the EuroQoL 5D (EQ-5D-5L™) |
| NCT02915744 (11) [back to overview] | Clinical Benefit Rate (CBR) |
| NCT02915744 (11) [back to overview] | Compare Health-Related Quality of Life (HRQoL) Using the Brief Fatigue Inventory (BFI) |
| NCT02915744 (11) [back to overview] | Compare Health-Related Quality of Life (HRQoL) Using the European Organisation for Treatment of Cancer (EORTC) Quality of Life Core 30 (QLQ-C30) Module With the Brain Neoplasms 20-question (BN-20) Subscale. |
| NCT02915744 (11) [back to overview] | Progression-Free Survival in Brain Metastasis (PFS-BM) |
| NCT02915744 (11) [back to overview] | Progression-Free Survival (Outside the Central Nervous System) |
| NCT02915744 (11) [back to overview] | Overall Survival (OS) of Patients |
| NCT02915744 (11) [back to overview] | Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3 |
| NCT02915744 (11) [back to overview] | Magnitude of Clinical Benefit Assessed by ESMO-MCBS Derived From Overall Survival |
| NCT02915744 (11) [back to overview] | Duration of Response (DoR) |
| NCT02953340 (10) [back to overview] | Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4 |
| NCT02953340 (10) [back to overview] | Number of Participants With Clinically Significant Laboratory Abnormalities |
| NCT02953340 (10) [back to overview] | Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4 |
| NCT02953340 (10) [back to overview] | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death |
| NCT02953340 (10) [back to overview] | Relative Dose Intensity (RDI) of TC Chemotherapy |
| NCT02953340 (10) [back to overview] | Depth of ANC Nadir in Cycle 1 |
| NCT02953340 (10) [back to overview] | Duration of Severe Neutropenia (DSN) in Cycle 1 |
| NCT02953340 (10) [back to overview] | Number of Participants With Febrile Neutropenia (FN) in Cycle 1 |
| NCT02953340 (10) [back to overview] | Number of Participants With Neutropenic Complications in Cycle 1 |
| NCT02953340 (10) [back to overview] | Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1 |
| NCT02965378 (5) [back to overview] | Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial) |
| NCT02965378 (5) [back to overview] | Progression-free Survival |
| NCT02965378 (5) [back to overview] | Duration of Response Among Patients Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1 |
| NCT02965378 (5) [back to overview] | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT02965378 (5) [back to overview] | Overall Survival |
| NCT02975934 (18) [back to overview] | PSA Response in Participants With a BRCA or ATM Alteration Combined |
| NCT02975934 (18) [back to overview] | Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined |
| NCT02975934 (18) [back to overview] | Interim Overall Survival in Participants With a BRCA Alteration |
| NCT02975934 (18) [back to overview] | Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined |
| NCT02975934 (18) [back to overview] | Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF |
| NCT02975934 (18) [back to overview] | Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling |
| NCT02975934 (18) [back to overview] | Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined |
| NCT02975934 (18) [back to overview] | Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration |
| NCT02975934 (18) [back to overview] | Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined |
| NCT02975934 (18) [back to overview] | Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration |
| NCT02975934 (18) [back to overview] | PSA Response in Participants With a BRCA Alteration |
| NCT02975934 (18) [back to overview] | Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined |
| NCT02975934 (18) [back to overview] | Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration |
| NCT02975934 (18) [back to overview] | Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P |
| NCT02975934 (18) [back to overview] | Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L |
| NCT02975934 (18) [back to overview] | Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration |
| NCT02975934 (18) [back to overview] | Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined |
| NCT02975934 (18) [back to overview] | Duration of Response (DOR) by IRR in Participants With a BRCA Alteration |
| 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] | Time to Death or Distant Metastases (TTDM) |
| NCT02998528 (4) [back to overview] | Event-Free Survival (EFS) |
| NCT02998528 (4) [back to overview] | Major Pathologic Response (MPR) Rate |
| NCT03041181 (1) [back to overview] | Number of Participants With Grade 3 or Grade 4 Adverse Events |
| NCT03043807 (1) [back to overview] | Time to Prostate-specific Antigen Recurrence |
| 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] | 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 |
| 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: 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: 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 B: Number of Participants With Best Overall Response as Per Investigator's Assessment |
| 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 A: Aetotal,14C: Total Cumulative Excretion of [14C]-Pevonedistat From the Body |
| 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: Aeurine: Cumulative Amount of Pevonedistat Dose Excreted in Urine at 144-168 Hours Post-dose |
| 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: Renal Clearance (CLR) for Pevonedistat |
| NCT03057366 (15) [back to overview] | Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
| NCT03093272 (5) [back to overview] | Overall Survival |
| NCT03093272 (5) [back to overview] | Serum PSA Change From Baseline to 12 Weeks on Treatment |
| NCT03093272 (5) [back to overview] | Maximum Blood Concentration (Cmax) for Docetaxel Pharmacokinetic Analysis |
| NCT03093272 (5) [back to overview] | To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide |
| NCT03093272 (5) [back to overview] | Area Under the Curve (AUC) for Docetaxel Pharmacokinetic Analysis |
| NCT03150875 (5) [back to overview] | Overall Survival |
| NCT03150875 (5) [back to overview] | Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE) |
| NCT03150875 (5) [back to overview] | Progression-free Survival by Investigators' Assessment |
| NCT03150875 (5) [back to overview] | Overall Response Rate (ORR) Per RECIST v1.1 as Assessed by Investigators |
| NCT03150875 (5) [back to overview] | Duration of Response (DOR) Per RECIST v1.1 as Assessed by Investigators |
| NCT03159143 (4) [back to overview] | Disease Control Rate (DCR) |
| NCT03159143 (4) [back to overview] | Overall Survival |
| NCT03159143 (4) [back to overview] | Response Rate |
| NCT03159143 (4) [back to overview] | Time to Progression (TTP) |
| NCT03211117 (3) [back to overview] | Number of Patients With Locoregional Recurrence and Locoregional Progression in the Thyroid Bed or Regional Lymph Nodes |
| NCT03211117 (3) [back to overview] | Overall Survival Rate |
| NCT03211117 (3) [back to overview] | Incidence of Adverse Events Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 |
| NCT03228186 (5) [back to overview] | The Percentage of Patients That Respond to Treatment |
| NCT03228186 (5) [back to overview] | The Number of Toxicities by System Organ Class |
| NCT03228186 (5) [back to overview] | Median Progression Free Survival Time |
| NCT03228186 (5) [back to overview] | The Number of Patients Who Achieve Stable Disease |
| NCT03228186 (5) [back to overview] | Median Overall Survival Time |
| NCT03246347 (1) [back to overview] | 52-week PSA Complete Response (CR) Rate |
| NCT03329378 (5) [back to overview] | Number of Participants Alive at the End of the Study |
| NCT03329378 (5) [back to overview] | Number of Participants With Pathologic Complete Response (pCR) |
| NCT03329378 (5) [back to overview] | Number of Cardiac Toxicity Events |
| NCT03329378 (5) [back to overview] | Number of Non-cardiac Toxicities |
| NCT03329378 (5) [back to overview] | Number of Participants With Breast Conservation |
| 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: 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 QRS 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: Cmax: Maximum Observed Plasma Concentration for Pevonedistat |
| NCT03338790 (9) [back to overview] | Number of Participants With Laboratory Values Change From Baseline |
| NCT03338790 (9) [back to overview] | Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3) |
| NCT03338790 (9) [back to overview] | Number of Participants With Laboratory Abnormalities in Specific Liver Tests |
| NCT03338790 (9) [back to overview] | Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests |
| NCT03338790 (9) [back to overview] | Number of Participants With Laboratory Values Change From Baseline |
| NCT03338790 (9) [back to overview] | Number of Participants With Laboratory Values Change From Baseline |
| NCT03338790 (9) [back to overview] | Number of Participants With Adverse Events (AEs) |
| NCT03338790 (9) [back to overview] | Number of Deaths |
| NCT03338790 (9) [back to overview] | Prostate-Specific Antigen Response Rate (RR-PSA) |
| NCT03430843 (15) [back to overview] | Duration of Response (DOR) in the PDL-1 Positive Analysis Set. |
| NCT03430843 (15) [back to overview] | Duration of Response (DOR) in the ITT Analysis Set |
| NCT03430843 (15) [back to overview] | Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C-30) in the ITT Analysis Set |
| NCT03430843 (15) [back to overview] | HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set |
| NCT03430843 (15) [back to overview] | HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set. |
| NCT03430843 (15) [back to overview] | HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set |
| NCT03430843 (15) [back to overview] | HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set |
| NCT03430843 (15) [back to overview] | HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set |
| NCT03430843 (15) [back to overview] | Number of Participants Experiencing Adverse Events (AEs) |
| NCT03430843 (15) [back to overview] | Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set |
| NCT03430843 (15) [back to overview] | Progression-free Survival (PFS) in the ITT Analysis Set |
| NCT03430843 (15) [back to overview] | Overall Survival (OS) in the PDL-1 Positive Analysis Set |
| NCT03430843 (15) [back to overview] | Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set |
| NCT03430843 (15) [back to overview] | Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets |
| NCT03430843 (15) [back to overview] | Objective Response Rate (ORR) in the ITT Analysis Set |
| NCT03449901 (5) [back to overview] | Progression-free Survival (PFS) (Cohort 1 Only) |
| NCT03449901 (5) [back to overview] | Safety and Tolerability of Regimen as Measured by Number and Grade of Adverse Events |
| NCT03449901 (5) [back to overview] | Number of Participants With Cancer-related Mortality (Cohort 1 Only) |
| NCT03449901 (5) [back to overview] | Clinical Benefit Rate (CBR) (Cohort 1 Only) |
| NCT03449901 (5) [back to overview] | Overall Survival (OS) (Cohort 1 Only) |
| NCT03474107 (9) [back to overview] | Duration of Response (DOR) as Per RECIST V1.1 |
| NCT03474107 (9) [back to overview] | Change From Baseline to Week 12 in European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Global Health Status (QL2 Score) |
| NCT03474107 (9) [back to overview] | Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS) |
| NCT03474107 (9) [back to overview] | Overall Survival (OS) |
| NCT03474107 (9) [back to overview] | Number of Participants With Treatment Emergent Adverse Events |
| NCT03474107 (9) [back to overview] | Disease Control Rate (DCR) as Per RECIST V1.1 |
| NCT03474107 (9) [back to overview] | Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) |
| NCT03474107 (9) [back to overview] | Number of Participants With ECOG Performance Status |
| NCT03474107 (9) [back to overview] | Overall Response Rate (ORR) as Per RECIST V1.1 |
| 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: 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: Total Clearance After Intravenous Administration (CL) for Pevonedistat Without Rifampin (Day 1) and With Rifampin (Day 10) |
| 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 B: Number of Participants With Best Overall Response as Per Investigator's Assessment |
| 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 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) |
| NCT03493854 (7) [back to overview] | Number of Participants With a Secondary Cardiac Event |
| NCT03493854 (7) [back to overview] | Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) |
| NCT03493854 (7) [back to overview] | Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4) |
| NCT03493854 (7) [back to overview] | Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline |
| NCT03493854 (7) [back to overview] | Number of Participants With a Primary Cardiac Event |
| NCT03493854 (7) [back to overview] | Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment |
| NCT03493854 (7) [back to overview] | Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) |
| NCT03626545 (28) [back to overview] | Randomized Part: Time to Definitive 10-point Deterioration in Global Health Status (GHS)/Quality of Life (QoL), Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire |
| NCT03626545 (28) [back to overview] | Randomized Part: Time to Definitive 10-point Deterioration (TTD) Symptom Scores of Chest Pain, Cough and Dyspnea Per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Lung Cancer (LC13) Questionnaire |
| NCT03626545 (28) [back to overview] | Randomized Part: Pre-dose Plasma Trough Concentration (CTrough) of Canakinumab |
| NCT03626545 (28) [back to overview] | Randomized Part: Cmax of Docetaxel |
| NCT03626545 (28) [back to overview] | Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire |
| NCT03626545 (28) [back to overview] | Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire |
| NCT03626545 (28) [back to overview] | Randomized Part: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores |
| NCT03626545 (28) [back to overview] | Randomized Part: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores |
| NCT03626545 (28) [back to overview] | Randomized Part: Change From Baseline in Chest Pain, Cough and Dyspnea Scores as Per the EORTC-QLQ LC13 Questionnaire |
| NCT03626545 (28) [back to overview] | Randomized Part: Change From Baseline in Chest Pain, Cough and Dyspnea Scores as Per the EORTC-QLQ LC13 Questionnaire |
| NCT03626545 (28) [back to overview] | Randomized Part: AUClast of Docetaxel |
| NCT03626545 (28) [back to overview] | Safety run-in Part: Time of Maximum Plasma Concentration (Tmax) of Canakinumab |
| NCT03626545 (28) [back to overview] | Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs) |
| NCT03626545 (28) [back to overview] | All Collected Deaths |
| NCT03626545 (28) [back to overview] | Safety run-in Part: Tmax of Docetaxel |
| NCT03626545 (28) [back to overview] | Safety run-in Part: AUClast of Docetaxel |
| NCT03626545 (28) [back to overview] | Randomized Part: Tmax of Docetaxel |
| NCT03626545 (28) [back to overview] | Disease Control Rate (DCR) |
| NCT03626545 (28) [back to overview] | Duration of Response (DOR) |
| NCT03626545 (28) [back to overview] | Overall Response Rate (ORR) |
| NCT03626545 (28) [back to overview] | Randomized Part: Canakinumab ADA Incidence On-treatment |
| NCT03626545 (28) [back to overview] | Randomized Part: Canakinumab Antidrug Antibodies (ADA) at Baseline |
| NCT03626545 (28) [back to overview] | Randomized Part: Overall Survival (OS) |
| NCT03626545 (28) [back to overview] | Safety run-in Part: Cmax of Docetaxel |
| NCT03626545 (28) [back to overview] | Randomized Part: Progression-Free Survival (PFS) |
| NCT03626545 (28) [back to overview] | Randomized Part: Time to Response (TTR) |
| NCT03626545 (28) [back to overview] | Safety run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Canakinumab |
| NCT03626545 (28) [back to overview] | Safety run-in Part: Maximum Plasma Concentration (Cmax) of Canakinumab |
| NCT03636256 (3) [back to overview] | Recurrence Free Survival (RFS) |
| NCT03636256 (3) [back to overview] | Disease Progression |
| NCT03636256 (3) [back to overview] | Incidence of Treatment Emergent Adverse Events (Safety and Tolerability) |
| NCT03647488 (19) [back to overview] | Maximum Plasma Concentration (Cmax) of Spartlizumab |
| NCT03647488 (19) [back to overview] | All Collected Deaths |
| NCT03647488 (19) [back to overview] | Run-in Part: Percentage of Participants With Adverse Events (AEs) |
| NCT03647488 (19) [back to overview] | Run-in Part: Percentage of Participants With at Least One Dose Interruption |
| NCT03647488 (19) [back to overview] | Run-in Part: Relative Dose Intensity Received by Participants |
| NCT03647488 (19) [back to overview] | Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment |
| NCT03647488 (19) [back to overview] | Progression Free Survival (PFS) |
| NCT03647488 (19) [back to overview] | Run-in Part: Percentage of Participants With at Least One Dose Reduction. |
| NCT03647488 (19) [back to overview] | Maximum Plasma Concentration (Cmax) of Capmatinib |
| NCT03647488 (19) [back to overview] | Spartalizumab ADA Incidence On-treatment |
| NCT03647488 (19) [back to overview] | Spartalizumab Antidrug Antibodies (ADA) Prevalence at Baseline |
| NCT03647488 (19) [back to overview] | AUClast of Capmatinib |
| NCT03647488 (19) [back to overview] | Time to Reach Maximum (Tmax) Plasma Concentration of Spartlizumab |
| NCT03647488 (19) [back to overview] | Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib |
| NCT03647488 (19) [back to overview] | Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment |
| NCT03647488 (19) [back to overview] | AUCtau of Spartlizumab |
| NCT03647488 (19) [back to overview] | AUCtau of Capmatinib |
| NCT03647488 (19) [back to overview] | AUClast of Spartlizumab |
| NCT03647488 (19) [back to overview] | Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs) |
| NCT03693612 (51) [back to overview] | Change From Baseline in Temperature-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Specific Gravity of Urine-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Specific Gravity of Urine-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Respiratory Rate-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Pulse Rate-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Oxygen Saturation-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Hemoglobin Level-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Hemoglobin Level-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Hematocrit Level-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Hematocrit Level-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Free Triiodothyronine (T3)-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Free Thyroxine (T4)-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Free Thyroxine (T4)-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Erythrocytes Count-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Erythrocytes Count-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Creatinine and Bilirubin Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Creatinine and Bilirubin Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Amylase and Lipase Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Amylase and Lipase Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Albumin and Total Protein Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Albumin and Total Protein Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Albumin and Total Protein Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Overall Response Rate-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1 |
| NCT03693612 (51) [back to overview] | Minimum Observed Plasma Concentration (Cmin) of Feladilimab-Part 1 |
| NCT03693612 (51) [back to overview] | Maximum Observed Plasma Concentration (Cmax) of Feladilimab-Part 1 |
| NCT03693612 (51) [back to overview] | Disease Control Rate-Part 1 |
| NCT03693612 (51) [back to overview] | Cmin of Tremelimumab-Part 1 |
| NCT03693612 (51) [back to overview] | Cmax of Tremelimumab-Part 1 |
| NCT03693612 (51) [back to overview] | AUC(0-t) of Tremelimumab-Part 1 |
| NCT03693612 (51) [back to overview] | Area Under the Plasma Concentration-time Curve (AUC[0-t]) of Feladilimab-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With Electrocardiogram (ECG) Findings |
| NCT03693612 (51) [back to overview] | Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With DLTs According to Severity-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participants With Abnormal Urinalysis Parameters-Part 1 |
| NCT03693612 (51) [back to overview] | Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1 |
| NCT03693612 (51) [back to overview] | Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1 |
| NCT03737123 (10) [back to overview] | PFS by irRECIST |
| NCT03737123 (10) [back to overview] | Clinical Benefit Rate (CBR) With RECIST 1.1 |
| 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] | Objective Response Rate (ORR) 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] | Progression Free Survival (PFS) Compared to Historical Controls |
| NCT03737123 (10) [back to overview] | Objective Response Rate (ORR) With irRECIST |
| NCT03737123 (10) [back to overview] | Progression Free Survival (PFS) |
| NCT03742986 (2) [back to overview] | Number of Participants Who Had a Pathological Complete Response (pCR) |
| NCT03742986 (2) [back to overview] | Number of Participants Who Had a Pathological Complete Response (pCR) |
| NCT03827473 (5) [back to overview] | Prostate Specific Antigen Progression Free Survival (PSA-PFS) |
| NCT03827473 (5) [back to overview] | Change in Quality of Life - PROMIS Fatigue |
| NCT03827473 (5) [back to overview] | Change in Quality of Life - FACT-P |
| NCT03827473 (5) [back to overview] | Prostate-specific Antigen (PSA) Response |
| NCT03827473 (5) [back to overview] | Change in Quality of Life - FACT/GOG-NTX |
| NCT03834506 (12) [back to overview] | Time to Prostate-specific Antigen (PSA) Progression |
| NCT03834506 (12) [back to overview] | Number of Participants Who Experienced an Adverse Event (AE) |
| NCT03834506 (12) [back to overview] | Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) |
| NCT03834506 (12) [back to overview] | Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST) |
| NCT03834506 (12) [back to overview] | Time to First Symptomatic Skeletal-related Event (SSRE) |
| NCT03834506 (12) [back to overview] | Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) |
| NCT03834506 (12) [back to overview] | Prostate-specific Antigen (PSA) Response Rate |
| NCT03834506 (12) [back to overview] | Overall Survival (OS) |
| NCT03834506 (12) [back to overview] | Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review |
| NCT03834506 (12) [back to overview] | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) |
| NCT03834506 (12) [back to overview] | Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review |
| NCT03834506 (12) [back to overview] | "Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 (Worst Pain in 24 Hours) and Opiate Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score" |
| NCT03837353 (5) [back to overview] | Number of Participants With a Best Overall Response of Complete Response (iCR) or Partial Response (iPR) Per iRECIST by End of Long-Term Follow-Up Period |
| NCT03837353 (5) [back to overview] | Maximal Percent Change in PSA Measured After Treatment Initiation |
| NCT03837353 (5) [back to overview] | Number of Dose Limiting Toxicities Observed by End of Treatment Cycle 1 |
| NCT03837353 (5) [back to overview] | Progression-Free Survival (PFS) |
| NCT03837353 (5) [back to overview] | Number of Participants With a Decline in Prostate-Specific Antigen (PSA) of at Least 50% Relative to Baseline |
| 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] | 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 |
| NCT03840915 (7) [back to overview] | Number of Participants With Dose-Limiting Toxicities (DLTs) |
| NCT03840915 (7) [back to overview] | Duration of Response (DOR) |
| NCT03840915 (7) [back to overview] | Number of Participants With Positive Antidrug Antibodies (ADA) |
| NCT03840915 (7) [back to overview] | Overall Survival (OS) |
| NCT03894891 (6) [back to overview] | Median Laryngectomy-free Survival (LFS) |
| NCT03894891 (6) [back to overview] | Median Laryngo-esophageal Dysfunction-free Survival (LEDFS) |
| NCT03894891 (6) [back to overview] | Number of Participants With Grade 3-5 Treatment-related Adverse Events |
| NCT03894891 (6) [back to overview] | EORTC QLQ-C30 Change in Emotional Functional Score From Baseline to Post IMRT+Nivolumab |
| NCT03894891 (6) [back to overview] | EORTC QLQ-C30 Change in Fatigue Score From Baseline to Post IMRT+Nivolumab |
| NCT03894891 (6) [back to overview] | Median Censoring Time for Overall Survival (OS) |
| NCT03933449 (11) [back to overview] | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus |
| NCT03933449 (11) [back to overview] | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) |
| NCT03933449 (11) [back to overview] | Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants |
| NCT03933449 (11) [back to overview] | Number of Participants Experiencing an Adverse Event (AE) |
| NCT03933449 (11) [back to overview] | Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE) |
| NCT03933449 (11) [back to overview] | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) |
| NCT03933449 (11) [back to overview] | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus |
| NCT03933449 (11) [back to overview] | Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants |
| NCT03933449 (11) [back to overview] | Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus |
| NCT03933449 (11) [back to overview] | Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10) |
| NCT03933449 (11) [back to overview] | Overall Survival (OS) in All Participants |
| NCT03971474 (8) [back to overview] | Overall Survival (OS), Subgroup Analysis by Stratification Factors |
| NCT03971474 (8) [back to overview] | Number of Participants With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs |
| NCT03971474 (8) [back to overview] | Investigator Assessed-progression-free Survival (IA-PFS) |
| NCT03971474 (8) [back to overview] | Disease Control Rate (DCR) |
| NCT03971474 (8) [back to overview] | Investigator-Assessed Progression-Free Survival (IA-PFS), Subgroup Analysis by Stratification Factors |
| NCT03971474 (8) [back to overview] | Response Rate (RR) |
| NCT03971474 (8) [back to overview] | Overall Survival (OS) |
| NCT03971474 (8) [back to overview] | Duration of Response (DOR) |
| NCT04024462 (3) [back to overview] | Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8) |
| NCT04024462 (3) [back to overview] | Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8) |
| NCT04024462 (3) [back to overview] | Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment |
| NCT04031885 (1) [back to overview] | Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) |
| NCT04145700 (7) [back to overview] | Pharmacokinetics (PK): Maximum Serum Concentration of Ramucirumab (Cmax) |
| NCT04145700 (7) [back to overview] | Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) |
| NCT04145700 (7) [back to overview] | Number of Participants With Treatment-Emergent Anti-Drug Antibodies (TE-ADA) |
| NCT04145700 (7) [back to overview] | Duration of Response (DoR) |
| NCT04145700 (7) [back to overview] | Complete Response (CR): Percentage of Participants Who Achieve CR |
| NCT04145700 (7) [back to overview] | Progression Free Survival (PFS) |
| NCT04145700 (7) [back to overview] | PK: Minimum Serum Concentration of Ramucirumab (Cmin) |
| NCT04165031 (2) [back to overview] | Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs) |
| NCT04165031 (2) [back to overview] | Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446 |
| NCT04303780 (1) [back to overview] | Progression-free Survival (PFS) |
| NCT04386746 (1) [back to overview] | 3-Month Complete Response Rate |
| NCT04471428 (12) [back to overview] | Time to Confirmed Deterioration in Patient-Reported Global Health Status (GHS) |
| NCT04471428 (12) [back to overview] | Minimum Plasma Concentration (Cmin) of Cabozantinib |
| NCT04471428 (12) [back to overview] | Confirmed Objective Response Rate (ORR) as Determined by Investigator |
| NCT04471428 (12) [back to overview] | Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab |
| NCT04471428 (12) [back to overview] | OS Rates |
| NCT04471428 (12) [back to overview] | PFS Rates Assessed by Investigator |
| NCT04471428 (12) [back to overview] | Overall Survival (OS) |
| NCT04471428 (12) [back to overview] | Maximum Serum Concentration (Cmax) of Atezolizumab |
| NCT04471428 (12) [back to overview] | Progression-Free Survival (PFS) as Determined by Investigator |
| NCT04471428 (12) [back to overview] | Duration of Response (DOR) as Determined by Investigator |
| NCT04471428 (12) [back to overview] | Time to Confirmed Deterioration in Patient-Reported Physical Functioning (PF) |
| NCT04471428 (12) [back to overview] | Minimum Serum Concentration (Cmin) of Atezolizumab |
| NCT04863248 (1) [back to overview] | Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0 |
| NCT04907227 (12) [back to overview] | Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) |
| NCT04907227 (12) [back to overview] | Time to Prostate-specific Antigen (PSA) Progression |
| NCT04907227 (12) [back to overview] | Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST) |
| NCT04907227 (12) [back to overview] | Time to First Symptomatic Skeletal-related Event (SSRE) |
| NCT04907227 (12) [back to overview] | Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) |
| NCT04907227 (12) [back to overview] | Overall Survival (OS) |
| NCT04907227 (12) [back to overview] | Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review |
| NCT04907227 (12) [back to overview] | Number of Participants Who Experienced an Adverse Event (AE) |
| NCT04907227 (12) [back to overview] | Prostate-specific Antigen (PSA) Response Rate |
| NCT04907227 (12) [back to overview] | Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review |
| NCT04907227 (12) [back to overview] | Number of Participants Who Discontinued Study Treatment Due To an Adverse Event (AE) |
| NCT04907227 (12) [back to overview] | "Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 (Worst Pain in 24 Hours) and Opiate Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score" |
| NCT05553808 (21) [back to overview] | Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline |
| NCT05553808 (21) [back to overview] | Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline |
| NCT05553808 (21) [back to overview] | Objective Response Rate |
| NCT05553808 (21) [back to overview] | Kaplan-Meier Estimates of iRECIST Progression-free Survival (iPFS) |
| NCT05553808 (21) [back to overview] | Minimum Observed Concentration (CmIn) of Feladilimab |
| NCT05553808 (21) [back to overview] | Overall Survival |
| NCT05553808 (21) [back to overview] | Kaplan-Meier Estimates of Progression-Free Survival (PFS) |
| NCT05553808 (21) [back to overview] | Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline |
| NCT05553808 (21) [back to overview] | Disease Control Rate (DCR) |
| NCT05553808 (21) [back to overview] | iRECIST Objective Response Rate (iORR) |
| NCT05553808 (21) [back to overview] | Kaplan-Meier Estimates of Duration of Response (DOR) in Participants With Objective Response |
| NCT05553808 (21) [back to overview] | Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable |
| NCT05553808 (21) [back to overview] | Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable |
| NCT05553808 (21) [back to overview] | Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline |
| NCT05553808 (21) [back to overview] | Kaplan-Meier Estimates of iRECIST Duration of Response (iDOR) in Participants With Objective Response |
| NCT05553808 (21) [back to overview] | Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline |
| NCT05553808 (21) [back to overview] | Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months |
| NCT05553808 (21) [back to overview] | Maximum Observed Concentration (Cmax) of Docetaxel |
| NCT05553808 (21) [back to overview] | Maximum Observed Concentration (Cmax) of Feladilimab |
| NCT05553808 (21) [back to overview] | Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals |
| NCT05553808 (21) [back to overview] | Number of Participants With Positive ADA Against Feladilimab |
Overall Survival
(NCT00003782)
Timeframe: 8 years
| Intervention | percentage of patients alive (Number) |
|---|
| Arm 1: Doxorubicin + Cyclophosphamide, Then Docetaxel | 83 |
| Arm 2: Doxorubicin + Docetaxel | 79 |
| Arm 3: Doxorubicin + Docetaxel + Cyclophosphamide | 79 |
Progression-Free Survival
Progression-Free Survival was defined as time from study entry to progression or to death without documentation of progression. A progression is defined as a significant increase in size of lesions present at the start of therapy or after a response. (NCT00004888)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.
| Intervention | months (Median) |
|---|
| Arm I: Doxorubicin and Taxotere | 11 |
| Arm II: Doxorubicin, Taxotere, and Herceptin | 10.6 |
Overall Survival
(NCT00004888)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.
| Intervention | months (Median) |
|---|
| Arm I: Doxorubicin and Taxotere | 24.6 |
| Arm II: Doxorubicin, Taxotere, and Herceptin | 31.8 |
Duration of Response
Defined as time from onset of PR or CR, whichever occurred first, until objective evidence of progression. (NCT00004888)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of November 21, 2007 is used for this report.
| Intervention | Months (Median) |
|---|
| Arm I: Doxorubicin and Taxotere | 10.1 |
| Arm II: Doxorubicin, Taxotere, and Herceptin | 14.7 |
Grades of Cardiotoxicity Events in the Subset of Patients Reporting a Cardiotoxicity Event
This table summarizes the cardiotoxicity events of different grades. Grade 1 is a decline of left ventricular ejection fraction(LVEF) >=10% but <20% of baseline value. Grade 2 is LVEF below LLN (50%) or decline of LVEF >=20% of baseline value. Grade 3 is congestive heart failure responsive to treatment. Please note that only a subset of patients reported cardiotoxic events so the totals will not add up to the total number of participants. (NCT00004888)
Timeframe: Baseline, after cycle 4 (~84 days), after cycle 8 (~168 days), and 30 or more days after last cycle of induction therapy
| Intervention | participants (Number) |
|---|
| Grade 1 After Cycle 4 (approx. 84 days) | Grade 1 After Cycle 8 (approx. 168 days) | Grade 1 After 30 days or more after last cycle | Grade 2 After Cycle 4 (approx 84 days) | Grade 2 After Cycle 8 (approx 168 days) | Grade 2 After 30 days or more after last cycle | Grade 3 After Cycle 4 (approx 84 days) | Grade 3 After Cycle 8 (approx 168 days) | Grade 3 After 30 days or more after last cycle |
|---|
| Arm I: Doxorubicin and Taxotere | 2 | 4 | 1 | 3 | 4 | 1 | 1 | 0 | 0 |
,| Arm II: Doxorubicin, Taxotere, and Herceptin | 12 | 8 | 10 | 0 | 2 | 5 | 0 | 0 | 0 |
Summary of Left Ventricular Ejection Fraction Values
This table summarizes the LVEF information at baseline, post Cycle 4, post Cycle 8, and 30 or more days after Cycle 8 on all treated patients and on the eligible subset. LVEF drops reported are absolute (not relative) drops. (NCT00004888)
Timeframe: Baseline, after cycle 4, after cycle 8, and 30 or more days after last cycle of induction therapy.
| Intervention | LVEF percent (Mean) |
|---|
| Baseline | Post Cycle 4 | Post Cycle 8 | greater than or equal to 30 days after cycle 8 | Baseline minus post cycle 4 | Baseline minus post cycle 8 | Baseline minus 30 days or more after cycle 8 |
|---|
| Arm I: Doxorubicin and Taxotere | 64.8 | 63 | 60.8 | 62.6 | 2.3 | 4.2 | 0.9 |
,| Arm II: Doxorubicin, Taxotere, and Herceptin | 62.9 | 61.7 | 58.9 | 59.1 | 1.6 | 4.9 | 6.2 |
Best Overall Response Using Eastern Cooperative Group Solid Tumor Response Criteria.
Please note that overall response includes CR and PR. CR is defined as complete disappearance of all clinically detectable malignant disease for at least 4 weeks. PR is 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. No change is defined as no significant change in measurable or evaluable disease for at least 4 weeks. Progression is defined as a significant increase in size of lesions present at the start of therapy or after a response. (NCT00004888)
Timeframe: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually until death or until reaching full study stop date. Data as of Nov 21, 2007 is used for this report. Please note that best overall response is reported in the table.
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | No Change | Progression | Unevaluable |
|---|
| Arm I: Doxorubicin and Taxotere | 1 | 17 | 11 | 6 | 3 |
,| Arm II: Doxorubicin, Taxotere, and Herceptin | 4 | 17 | 11 | 9 | 5 |
Overall Clinical Response Rate
Overall response rate is defined as the percentage of participants with a CR (complete disappearance of all target lesions), PR (a 30% decrease in the sum of the longest diameter of target lesions) determined by clinical measurements per the Response Evaluation Criteria in Solid Tumors (RECIST) and/or a complete pathologic response (disappearance of all invasive tumor pathologically or presence of ductal carcinoma in situ) per the Chevallier criteria. For details about the RECIST or Chevallier criteria see the protocol link module. (NCT00005908)
Timeframe: 6 years
| Intervention | Percentage of participants (Number) |
|---|
| Complete Response | Partial Response | Complete pathologic response |
|---|
| Dose A & B-Cohort 1 & 2-Arm 1& 2-Docetaxel & Capecitabine | 31 | 59 | 10 |
Number of Participants, e.g. Responders and Non-responders With a Percent Change in Expression Patterns After Chemotherapy With Changes in Expression Patterns After Chemotherapy in Preclinical Models
Patients were classified as responders or non-responders based on change in tumor size by clinical exam and pathologic response.For instance, patients with a pathological complete response, micro-invasive disease at surgery, or clinical complete response after four cycles of treatment were considered responders. Changes in gene expression associated with treatment was assessed before/after chemotherapy. All gene expression summary intensities below 50 were thresholded to the value of 50 and genes showing variability significantly smaller than the median gene variability were screened out. (NCT00005908)
Timeframe: 6 years
| Intervention | Participants (Number) |
|---|
| Responders | Non-responders |
|---|
| Dose A & B-Cohort 1 & 2-Arm 1 & 2-Docetaxel & Capecitabine | 8 | 13 |
Complementary Deoxyribonucleic Acid (cDNA) Expression
Patients were classified as responders or non-responders based on change in tumor size by clinical exam and pathologic response.For instance, patients with a pathological complete response, micro-invasive disease at surgery, or clinical complete response after four cycles of treatment were considered responders. Changes in gene expression associated with treatment was assessed before/after chemotherapy. All gene expression summary intensities below 50 were thresholded to the value of 50 and genes showing variability significantly smaller than the median gene variability were screened out. (NCT00005908)
Timeframe: 6 years
| Intervention | Participants (Number) |
|---|
| Responders | Non-responders |
|---|
| Dose A-Cohort 1-Arm 1-Docetaxel & Capecitabine | 8 | 2 |
,| Dose B-Cohort 2-Arm 2 Reduced Dose-Docetaxel & Capecitabine | 7 | 13 |
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For the detailed list of adverse events see the adverse event module. (NCT00005908)
Timeframe: 6 years
| Intervention | Participants (Number) |
|---|
| Dose A-Cohort 1-Arm 1-Docetaxel & Capecitabine | 9 |
| Dose B-Cohort 2-Arm 2 Reduced Dose-Docetaxel & Capecitabine | 20 |
Number of Participants With 5-year Freedom From Prostate Specific Antigen (PSA) Recurrence.
Number of participants that experienced 5-year freedom from Prostate Specific Antigen (PSA) recurrence (PSA > 0.4 ng/ml confirmed by a second PSA that is higher than the first by any amount (2)) in men with high risk localized prostate cancer treated with neoadjuvant docetaxel/mitoxantrone followed by surgery. (NCT00017563)
Timeframe: Every 3 months after surgery for up to 5 years.
| Intervention | participants (Number) |
|---|
| Docetaxel and Mitox | 30 |
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
| Intervention | percentage 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 |
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
| Intervention | percentage 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 |
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
| Intervention | percentage 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 |
Overall Survival From Randomization
Overall survival (OS) was computed using the number of months from the date of randomization to the date of death. Participants still alive were censored at the last follow-up date. Kaplan-Meier methodology was used to evaluate OS. (NCT00024167)
Timeframe: Followed every 4 weeks from randomization until death, up to 7 years.
| Intervention | months (Median) |
|---|
| Induction Treatment + Strontium-89 | 24.2 |
| Induction Treatment + No Strontium-89 | 22.8 |
Overall Survival From Registration
Overall survival (OS) was computed using the number of months from the date of registration to the date of death. Participants still alive were censored at the last follow-up date. Kaplan-Meier methodology was used to evaluate OS. (NCT00024167)
Timeframe: Followed every 4 weeks from registration until death, up to 7 years.
| Intervention | months (Median) |
|---|
| Induction Treatment + Strontium-89 | 27.9 |
| Induction Treatment + No Strontium-89 | 26.6 |
Progression-free Survival
(NCT00041067)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | 20 |
Response Rate (Complete and Partial, Confirmed and Unconfirmed)
Response was measured by the RECIST criteria. A patient was considered a responder if there was confirmed or unconfirmed partial or complete response. All others were considered non-responders even if the patient was technically not assessable due to different measurement techniques at the two time points. (NCT00041067)
Timeframe: response assessed after every 3 cycles (9 weeks) during treatment for up to 3 years if no progession
| Intervention | participants (Number) |
|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | 53 |
Toxicity
Number of patients for whom highest grade of toxicity observed during treatment. Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT00041067)
Timeframe: toxicities assessed every 3 weeks during treatment, for up to 3 years if no progession
| Intervention | Participants (Number) |
|---|
| Alkaline phosphatase increase | Anemia | Arthralgia | Bone pain | Catheter related infection | Chest pain,not cardio or pleur | Dehydration | Depression | Diarrhea without colostomy | Dyspepsia/heartburn | Dyspnea | Fatigue/malaise/lethargy | Febrile neutropenia | Headache | Hyperglycemia | Hypermagnesemia | Hypokalemia | Hypophosphatemia | Hypotension | Hypoxia | Infection w/o 3-4 neutropenia | Infection with 3-4 neutropenia | LVEF decrease/CHF | Leukopenia | Lymphopenia | Muscle weakness (not neuro) | Nausea | Neutropenia/granulocytopenia | PRBC transfusion | Pain-other | Pericar. effusion/pericarditis | Pneumonitis/infiltrates | Respiratory infect w/ neutrop | Respiratory infection, unk ANC | SGPT (ALT) increase | Sensory neuropathy | Syncope | Tearing | Thrombosis/embolism | Transplant-pRBC transfusion | Vomiting |
|---|
| Docetaxel + Vinorelbine + G-CSF + Trastuzumab | 1 | 7 | 1 | 2 | 2 | 2 | 1 | 1 | 2 | 1 | 2 | 9 | 4 | 3 | 6 | 1 | 2 | 1 | 1 | 1 | 4 | 1 | 1 | 11 | 2 | 1 | 3 | 16 | 1 | 3 | 1 | 3 | 1 | 1 | 1 | 5 | 1 | 1 | 1 | 1 | 2 |
Survival at 1 Year
(NCT00041067)
Timeframe: 1 year
| Intervention | percentage of patients (Number) |
|---|
| Trastuzumab, Docetaxel, Vinorelbine and Filgrastim | 93 |
Epidermal Growth Factor Receptor (EGFR) Status
EGFR expression was be evaluated by staining 5-micron paraffin sections of tumor biopsies with anti-EGFR clone 2-18C9 (DAKO Corporation, Carpinteria, CA) using an indirect immunoperoxidase technique according to the instructions provided by DAKO. In brief, this includes an antigen retrieval pretreatment, the blocking of endogenous peroxidase activity, incubation with anti-EGFR antibody or a negative reagent control, staining with a detection system, visualization, and coverslipping. (NCT00042939)
Timeframe: Original tumor tissue samples submitted within one month of patient randomization
| Intervention | participants (Number) |
|---|
| Positive | Negative |
|---|
| Arm A: Irinotecan/Docetaxel | 29 | 1 |
,| Arm B: Irinotecan/Docetaxel/Cetuximab | 30 | 1 |
Proportion of Patients With Thromboembolic Events
To determine the rate of thromboembolic events in this population when prophylactic enoxaparin sodium is administered. (NCT00042939)
Timeframe: Assessed every 6 weeks while on treatment and for 30 days after the end of treatment
| Intervention | Proportion of participants (Number) |
|---|
| Arm A: Irinotecan/Docetaxel | 0 |
| Arm B: Irinotecan/Docetaxel/Cetuximab | 0.023 |
Proportion of Patients With Objective Response Evaluated by RECIST (Solid Tumor Response Criteria)
"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" (NCT00042939)
Timeframe: Assessed every 12 weeks until progression
| Intervention | Proportion of participants (Number) |
|---|
| Arm A: Irinotecan/Docetaxel | 0.045 |
| Arm B: Irinotecan/Docetaxel/Cetuximab | 0.07 |
Progression-free Survival
"Progression-free survival was defined as the shorter of:~The time from registration to progression. or~The time from registration to death without documentation of progression given that the death occured within 4 months of the last disease assessment without progression (or registration, whichever is more recent).~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." (NCT00042939)
Timeframe: Assessed every 3 months for 2 years and then every 6 months for 1 year
| Intervention | months (Median) |
|---|
| Arm A: Irinotecan/Docetaxel | 3.9 |
| Arm B: Irinotecan/Docetaxel/Cetuximab | 4.5 |
Overall Survival
Overall survival was defined as time from registration to death from any cause. (NCT00042939)
Timeframe: Assessed every 3 months for 2 years and then every 6 months for 1 year
| Intervention | months (Median) |
|---|
| Arm A: Irinotecan/Docetaxel | 6.5 |
| Arm B: Irinotecan/Docetaxel/Cetuximab | 5.3 |
Percentage of Participants With Reoccurrence
Percentage of participants where number with local recurrence, distant metastasis, or death of any cause at 50 months is divided by total number of participants and used as primary efficacy end point to compare paclitaxel to combination docetaxel and capecitabine in breast cancer treatment for preventing recurrence (return of cancer). (NCT00050167)
Timeframe: Median of 50 months
| Intervention | participants (Log Mean) |
|---|
| Weekly Paclitaxel (WP) | 90.7 |
| Docetaxel and Capecitabine (DX) | 87.5 |
Progression Free Survival(PFS)
Progression free survival was defined as time from the start of treatment to the date of cancer progression, or death, and censored at the date of last follow-up for those without disease progression and still alive. Stable disease is measured from the start of the treatment until progression, taking as reference the smallest measurements recorded since the treatment started. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT00054275)
Timeframe: 3 years
| Intervention | months (Median) |
|---|
| Docetaxel and OSI-774 | 8.4 |
Disease Response (Tumor Measurements)Per RECIST Criteria v. 2000
Response and progression will be evaluated in this study using the criteria by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. Partial Response: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions. Progressive Disease: At least a 20% increase in the sum of the LD of target lesions. Stable Disease: Neither sufficient shrinkage nor sufficient increase. (NCT00054275)
Timeframe: after 6 course (6 months) of combination therapy
| Intervention | participants (Number) |
|---|
| Partial response | Disease progression | Stable disease |
|---|
| Docetaxel and OSI-774 | 11 | 14 | 3 |
Overall Survival as of 2008
Overall survival (OS) was defined as time from the start of treatment to death, and censored at the time of last assessment for survivors. (NCT00054275)
Timeframe: 5 yrs
| Intervention | months (Median) |
|---|
| Docetaxel and OSI-774 | 22.3 |
Adverse Events
Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT00062439)
Timeframe: Weekly for the first 13 weeks, then every 3 weeks for the next 6 weeks.
| Intervention | Participants (Number) |
|---|
| Adult respiratory distress syndrome (ARDS) | Allergic reaction/hypersensitivity | Chylothorax | Dehydration | Diarrhea | Dyspnea (shortness of breath) | Esophagitis | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Fistula, pulmonary/upper respiratory - Bronchus | Fistula, pulmonary/upper respiratory - Lung | Glucose, serum-high (hyperglycemia) | Hemoglobin | Hemorrhage/bleeding w/surgery, intra- or post-op | Hypoxia | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | Inf (clin/microbio) w/Gr 3-4 neuts - Wound | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | Inf w/normal ANC or Gr 1-2 neutrophils - Meninges | Inf w/normal ANC or Gr 1-2 neutrophils - Wound | Infection with unknown ANC - Lung (pneumonia) | Infection with unknown ANC - Wound | Leak, cerebrospinal fluid (CSF) | Leukocytes (total WBC) | Lymphopenia | Metabolic/Laboratory-Other (Specify) | Mucositis/stomatitis (clinical exam) - Esophagus | Nausea | Neutrophils/granulocytes (ANC/AGC) | Pain - Chest wall | Pain - Extremity-limb | Pain-Other (Specify) | Platelets | Pulmonary/Upper Respiratory-Other (Specify) | SVT and nodal arrhythmia - Atrial fibrillation | Sodium, serum-low (hyponatremia) | Thrombosis/thrombus/embolism | Ventricular arrhythmia - Ventricular fibrillation | Vomiting | Weight loss |
|---|
| Consolidation Docetaxel | 0 | 0 | 0 | 2 | 1 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 6 | 2 | 0 | 0 | 1 | 8 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
,| Induction Cisplatin/Etoposide + XRT | 0 | 1 | 0 | 2 | 1 | 0 | 1 | 2 | 2 | 0 | 0 | 0 | 3 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 11 | 3 | 1 | 1 | 1 | 15 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 2 | 0 |
,| Surgery | 3 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 4 | 1 | 3 | 0 | 0 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 |
Response
Response was defined as achieving a confirmed or unconfirmed complete or partial response as determined by RECIST. Patients who dropped out due to any cause prior to getting their response assessment were counted as non-responders. A complete response (CR) was defined as disappearance of all disease. A partial response was defined as a >= 30% decrease in the sum of longest diameters of target lesions. A CR or PR was defined as confirmed if two consecutive determinations were documented at least 4 weeks apart. (NCT00062439)
Timeframe: After completion of induction therapy.
| Intervention | percentage of participants (Number) |
|---|
| Induction Cisplatin/Etoposide + XRT/Surgery/Consolidation Chem | 28 |
Progression-Free Survival at 3 Years
Duration from date of enrollment to date of progression (per RECIST), symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free were censored at the date of last contact. (NCT00062439)
Timeframe: At the completion of induction therapy, then again 4 weeks after the completion of consolidation therapy, then every 3 months for 2 years, then every 6 months until up to a maximum of 5 years after enrollment.
| Intervention | percentage of patients (Number) |
|---|
| Induction Cisplatin/Etoposide + XRT/Surgery/Consolidation Chem | 56 |
Overall Survival
The duration from the date of enrollment until the date of death due to any cause. Patients last known to be alive were censored at the date of last contact. (NCT00062439)
Timeframe: daily for 12 weeks then every 3 weeks for 12 weeks, then every 6 months thereafter.
| Intervention | years (Median) |
|---|
| Induction Cisplatin/Etoposide + XRT/Surgery/Consolidation Chem | 4 |
Feasibility of Treating Patients With Stage IIB/IIIB Pancoast Tumors With a Regimen of Cisplatin and Etoposide Plus Concurrent Radiotherapy Followed by Surgical Resection Followed by Consolidation Therapy With Docetaxel.
Feasibility was assessed by estimating the percentage of participants who would be able to complete the entire treatment regimen. (NCT00062439)
Timeframe: After completion of 5 weeks of radiotherapy given concurrently with cisplatin+etoposide, surgery + 8 weeks of recovery time, and 6 weeks of consolidation therapy with docetaxel
| Intervention | percentage of participants (Number) |
|---|
| Induction Cisplatin/Etoposide + XRT/Surgery/Consolidation Chem | 45 |
Clinical Imaging Responses
Evaluation target lesions (clinical response) by physical exam/ultrasound measurements of primary tumor and axillary lymph nodes after 3-6 courses: Complete Response: Disappearance of all target lesions; Partial Response: >30% decrease in sum longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease: >20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1>new lesions; Stable Disease: Neither sufficient shrinkage for PR nor increase for PD, reference smallest sum LD since treatment started. (NCT00063934)
Timeframe: After 3 and 6 courses of 21 day treatments (up to 18 weeks)
| Intervention | participants (Number) |
|---|
| CR | PR |
|---|
| Oblimersen Plus Doxorubicin + Docetaxel | 30 | 0 |
Number of Participants With Pathologic Complete Response (pCR)
Pathologic complete responses (pCR), defined as no evidence of residual invasive tumor, including no residual tumor in the axillary lymph nodes, measured by microscopic evaluation of tissue specimen at time of definitive surgery (after 6 courses of neoadjuvant therapy). Neoadjuvant (preoperative) therapy administered on the first five days of every 3-week cycle. Response Evaluation Criteria in Solid Tumors (RECIST) Committee [JNCI 92(3):205-216, 2000] (NCT00063934)
Timeframe: At time of definitive surgery (after 6 courses of neoadjuvant therapy in 3 week cycles), approximately 18 weeks
| Intervention | Participants (Number) |
|---|
| Oblimersen Plus Doxorubicin + Docetaxel | 0 |
Number of Participant With Toxicities
(NCT00063934)
Timeframe: From baseline until the date of first documented toxicity or date of death from any cause, whichever came first, assessed every three weeks up to 2 years and 5 months
| Intervention | Participants (Count of Participants) |
|---|
| Oblimersen Plus Doxorubicin + Docetaxel | 30 |
Bcl-2 Expression in Breast Cancer Tissue
Number of participant with Bcl-2 Expression in breast cancer tissue by protein and mRNA expression before treatment and at 3-5 days after oblimersen treatment. (NCT00063934)
Timeframe: before treatment and at 3-5 days after oblimersen treatment
| Intervention | participants (Number) |
|---|
| Oblimersen Plus Doxorubicin + Docetaxel | 30 |
Number of Participants With Grade 1, 2, 3 or 4 Hematologic Toxicities
Hematology parameters included hemoglobin, hematocrit, red blood cell count, white blood cell count with differential leukocyte and platelet count. Differential to include total neutrophils, bands, lymphocytes, monocytes, eosinophil, and basophils. Recording of any hematology toxicity grade was done using National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 2.0. Higher the grade, more is the toxicity. Data for number of participants with grade 1, 2, 3 or 4 hematologic toxicities have been presented. (NCT00065182)
Timeframe: Up to 16 months
| Intervention | Participants (Count of Participants) |
|---|
| Hemoglobin, Grade 1 | Hemoglobin, Grade 2 | Hemoglobin, Grade 3 | Neutrophils, Grade 1 | Neutrophils, Grade 2 | Neutrophils, Grade 3 | Neutrophils, Grade 4 | Platelets, Grade 1 | Platelets, Grade 2 | Platelets, Grade 3 | Platelets, Grade 4 | White blood cell, Grade 1 | White blood cell, Grade 2 | White blood cell, Grade 3 | White blood cell, Grade 4 |
|---|
| IV Docetaxel | 107 | 46 | 11 | 14 | 7 | 7 | 11 | 10 | 3 | 0 | 0 | 28 | 14 | 13 | 2 |
,| IV Topotecan + IV Docetaxel | 76 | 95 | 18 | 27 | 37 | 47 | 20 | 75 | 20 | 18 | 1 | 38 | 51 | 50 | 15 |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
AE is defined as any untoward medical occurrence in a participant, 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. SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or it is considered to be medically significant. (NCT00065182)
Timeframe: Up to 16 months
| Intervention | Participants (Count of Participants) |
|---|
| Any AEs | Any SAEs |
|---|
| IV Docetaxel | 172 | 49 |
,| IV Topotecan + IV Docetaxel | 186 | 58 |
Number of Participants With Clinically Significant Abnormal Vital Signs Data
Vital sign parameters included (blood pressure, and pulse rate after five minutes sitting, body temperature). Blood pressure and pulse rate was measured after sitting for 5 minutes. Only participants with clinically significant abnormal Vital sign data was reported. (NCT00065182)
Timeframe: Up to 16 months
| Intervention | Participants (Count of Participants) |
|---|
| IV Topotecan + IV Docetaxel | 0 |
| IV Docetaxel | 0 |
Number of Participants With Grade 3 or 4 Clinical Chemical Toxicities
Standard chemistry evaluation included sodium, potassium, chloride, bicarbonate, calcium, phosphorous, magnesium, blood urea nitrogen (BUN)/urea, uric acid, creatinine, lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, total protein and albumin. Recording of any hematology toxicity grade was done using National Cancer Institute - Common Toxicity Criteria for Adverse Events (NCI CTCAE) version 2.0. Higher the grade, more is the toxicity. Data for number of participants with grade 3 or 4 clinical chemical toxicities have been presented. (NCT00065182)
Timeframe: Up to 16 months
| Intervention | Participants (Count of Participants) |
|---|
| Albumin, Grade 3 | BUN/Urea, Grade 3 | Creatinine, Grade 3 | Alkaline Phosphatase, Grade 3 | AST, Grade 3 | AST, Grade 4 | ALT, Grade 3 | ALT, Grade 4 | Bilirubin, Grade 3 | Sodium, Grade 3 | Sodium, Grade 4 | Calcium, Grade 3 | Calcium, Grade 4 | Potassium, Grade 3 | Potassium, Grade 4 | Magnesium, Grade 3 |
|---|
| IV Docetaxel | 3 | 2 | 1 | 1 | 1 | 0 | 0 | 0 | 2 | 9 | 1 | 2 | 1 | 3 | 1 | 2 |
,| IV Topotecan + IV Docetaxel | 3 | 4 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 12 | 0 | 2 | 0 | 7 | 1 | 4 |
Number of Participants With Thromboembolic Events
(NCT00066677)
Timeframe: 93 days
| Intervention | participants (Number) |
|---|
| rhuMAB-VEGF | 3 |
| rhuMAB-VEGF and Docetaxel | 2 |
Overall Survival
(NCT00066677)
Timeframe: From date of registration until the date of death, assessed up to 5 years
| Intervention | days (Median) |
|---|
| rhuMAB-VEGF | 165 |
| rhuMAB-VEGF and Docetaxel | 125 |
Progression-free Survival
(NCT00066677)
Timeframe: 4 months
| Intervention | days (Median) |
|---|
| rhuMAB-VEGF | 43 |
| rhuMAB-VEGF and Docetaxel | 48 |
Objective Response Rate
(NCT00066677)
Timeframe: 56 days
| Intervention | participants (Number) |
|---|
| rhuMAB-VEGF | 0 |
| rhuMAB-VEGF and Docetaxel | 0 |
Tumor Response Assessment
Measured by physical examination compared to breast mammography and MRI assessment (NCT00068341)
Timeframe: 5 years
| Intervention | participants (Number) |
|---|
| Arm I: Her2 + | 6 |
| Arm II: Her2 + | 1 |
| Arm III: Her - | 12 |
Clinical Tumor Response by Physical Exam and Imaging Studies
(NCT00068341)
Timeframe: 5 years
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Marginal Response |
|---|
| Arm I: Her2+ | 8 | 7 | 0 |
,| Arm II:Her2+ | 5 | 7 | 1 |
,| Arm III: Her2- | 18 | 21 | 4 |
Clinico-histologic Predictors of pCR (Pathologic Complete Response)
(NCT00068341)
Timeframe: 5 years
| Intervention | participants (Number) |
|---|
| ER-negative | ER-positive | PR-negative | PR-positive | ER and PR both negative | ER and PR one negative | ER and PR both positive | HER2 negative | HER2 positive | T-Stage T2 | T-Stage T3 | T-Stage T4 | Tumor Type - IDC only | Tumor Type - all others (compared to IDC only) | Tumor Type - ILC only | Tumor Type - all other comparted to (ICL only) | Triple Negative-yes | Triple Negative-no | FISH positive Herceptin No | FISH positive Herceptin Yes |
|---|
| Pathologic CR - No | 14 | 38 | 24 | 28 | 14 | 10 | 28 | 30 | 22 | 9 | 27 | 16 | 38 | 14 | 9 | 43 | 5 | 38 | 13 | 9 |
,| Pathologic CR - Yes | 11 | 8 | 14 | 5 | 9 | 7 | 3 | 12 | 7 | 5 | 13 | 1 | 19 | 0 | 0 | 19 | 6 | 7 | 1 | 6 |
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
| Intervention | participants (Number) |
|---|
| DFS (Disease Free Survival) | OS (overall survival) |
|---|
| Arm I: HER2+ | 13 | 13 |
,| Arm II: HER2+ | 8 | 11 |
,| HER2- | 33 | 39 |
,| Total | 54 | 63 |
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
| Intervention | participants (Number) |
|---|
| N(0) | N+ |
|---|
| Arm I (Pre-op TCH) | 9 | 6 |
,| Her2- (Pre-op TC) | 21 | 23 |
,| Her2+ (Pre-op TC, Post-op Herceptin) | 4 | 11 |
Geometric Mean of Maximum Concentration of the Drug (Cmax)
In the first cycle patients were to receive docetaxel on days 1 and 8 and to be randomized to receive tariquidar on either day 1 or 8. Thus pharmacokinetic data with and without tariquidar can be compared. (NCT00069160)
Timeframe: 24 hours
| Intervention | Cmax (ng/mL) (Geometric Mean) |
|---|
| C1D1 | C1D8 | Both Groups (C1D1 + C1D8) |
|---|
| Docetaxel Alone | 1315 | 1060 | 1190 |
,| With Tariquidar | 1093 | 1026 | 1063 |
Clinical Response Rate
Response is determined by RECIST criteria defined as changes in only the largest diameter (unidimensional measurement) of the tumor lesion. Lesions are either measurable or non-measurable. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >/- 20 mm with conventional techniques (CT, MRI, xray) or as >/- 10 mm with a spiral CT scan. Non-measurable lesions are defined as all other lesions (or sites of disease) including small lesions (longest diameter <20 mm with conventional techniques or <10 mm using spiral CT. (NCT00069160)
Timeframe: 4 years, 8-11 months
| Intervention | Percentage of participants (Number) |
|---|
| All Patients Who Received Docetaxel and Tariquidar | 8 |
Percent Increase in Sestamibi Area Under Curve (AUC) in Liver After Tariquidar
A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P<0.001. A secondary objective of this study was to establish whether tariquidar (150 mg) modulates Pgp in liver. Sestamibi is a Pgp substrate that may be a surrogate for measuring drug efflux from tumors. A baseline Tc-sestamibi scan was obtained before the administration of tariquidar. A minimum of 48 hours later, on or about day 22 a single dose of tariquidar was administered, followed by a second Tc-sestamibi scan. (NCT00069160)
Timeframe: 3 - 24 hours
| Intervention | percent increase in sestamibi AUC (Median) |
|---|
| All Patients Who Received Docetaxel and Tariquidar | 82.2 |
Percent Increase in Sestamibi Area Under Curve (AUC) in Tumor Tissue
99mTc-sestamibi is a radionuclide imaging agent used to study cardiac function that has also been shown to be a substrate for P-glycoprotein- mediated drug efflux. Because of the high expression of Pgp in liver tissue, sestamibi uptake in liver tissue is often monitored as a marker of Pgp inhibition. A significant change in the area under the curve(AUC) in liver tissue (normal tissue as a surrogate) is defined as P<0.001. (NCT00069160)
Timeframe: 3-24 hours
| Intervention | Percent (Median) |
|---|
| All Patients Who Received Docetaxel and Tariquidar | 12.4 |
The Number of Participants With Adverse Events.
Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module. (NCT00069160)
Timeframe: 4 yrs 8-11 months
| Intervention | participants (Number) |
|---|
| Patients on Docetaxel on Days 1, 8 & Tariquidar on Day 8, 22 | 23 |
| Patients on Docetaxel on Days 1, 8 & Tariquidar on Days 1, 22 | 25 |
Geometric Mean of Area Under Curve (AUC0)-24
(NCT00069160)
Timeframe: 24 hours
| Intervention | h*ng/mL (Geometric Mean) |
|---|
| C1D1 | C1D8 | Both Groups (C1D1 + C1D8) |
|---|
| Docetaxel Alone | 1367 | 1308 | 1339 |
,| With Tariquidar | 1409 | 1327 | 1373 |
Objective Response Rate
Patients will be evaluated up to 4 time points(after 2,4,8 and 12 cycles of therapy), each cycle is 21 days. Per RECIST 1.0 and assessed by CT/MRI disease status will be categorized as R=CR/PR(response), F=progressive disease or death(failure), or S(stable disease=neither R nor F) based on the change from baseline. A patient with outcome R or F at any stage is scored as having that overall outcome, a patient with outcome S is re-evaluated after subsequent cycles of therapy. Patients who receive more than 14 cycles of therapy will be scored as the outcome at completion of cycle 14. (NCT00073983)
Timeframe: After 2, 4, 8 and 12 cycles of therapy, each cycle is 21 days
| Intervention | participants (Number) |
|---|
| Ewing's Sarcoma | 6 |
| Osteosarcoma | 5 |
| Chondrosarcoma | 14 |
Toxicity as Assessed by NCI CTCAE v3.0
Toxicity was graded according to Common Terminology Criteria for Adverse Events v.3.0 (CTCAE v.3.0). For gemcitabine or docetaxel related grade 3 or 4 non-hematological toxicities or hematological toxicities (grade 3 or 4 neutropenia for ≥ 7 days, grade 4 thrombocytopenia, or any platelet transfusion), both agents were withheld until the toxicity was ≤ grade 1. If the toxicity recovered to ≤ grade 1 by cycle day 35, the dose of both agents was reduced for all subsequent cycles. If the toxicity did not resolve by day 35, protocol therapy was discontinued. (NCT00073983)
Timeframe: Throughout the study
| Intervention | participants (Number) |
|---|
| Toxicity | No Toxicity |
|---|
| Chondrosarcoma | 5 | 20 |
,| Ewing's Sarcoma | 4 | 10 |
,| Osteosarcoma | 3 | 11 |
Percentage of Participants With Objective Response (OR) for Phase 2 (Double-blind)
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses 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 percent (%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. (NCT00076024)
Timeframe: Phase 2 double- blind baseline until the date of first documented progression or discontinuation from the study treatment due to any cause, assessed every 9 weeks up to 129 weeks
| Intervention | percentage of participants (Number) |
|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | 41.1 |
| Docetaxel + Placebo (Phase 2, Double-blind) | 23.6 |
Percentage of Participants With Objective Response (OR) for Phase 2 (Open-label)
Percentage of participants with OR based assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses 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. (NCT00076024)
Timeframe: Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks
| Intervention | percentage of participants (Number) |
|---|
| Axitinib (Phase 2, Open-label) | 6.3 |
Duration of Response (DR) for Phase 2 (Double-blind)
Time in days from the first documentation of objective tumor response 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 cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. (NCT00076024)
Timeframe: Phase 2 double-blind baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 9 weeks up to 129 weeks
| Intervention | days (Median) |
|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | 211 |
| Docetaxel + Placebo (Phase 2, Double-blind) | 149 |
Duration of Response (DR) for Phase 2 (Open-label)
Time in days from the first documentation of objective tumor response 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 cancer minus the date of the first CR or PR that was subsequently confirmed plus 1. DR was calculated for the subgroup of participants with a confirmed objective tumor response. (NCT00076024)
Timeframe: Phase 2 open-label baseline until the date of first documented progression or discontinuation from the study due to any cause, assessed every 8 weeks up to 58 weeks
| Intervention | days (Median) |
|---|
| Axitinib (Phase 2, Open-label) | 1.0 |
Time to Tumor Progression (TTP)
Time in days from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever comes first. TTP was calculated as first event date minus the date of first dose of study medication plus 1. Tumor progression was determined from oncologic assessment data (where data meet the criteria for progressive disease [PD]). (NCT00076024)
Timeframe: Phase 2 double-blind baseline until tumor progression or death or discontinuation from study treatment, assessed every 9 weeks up to 129 weeks
| Intervention | days (Median) |
|---|
| Axitinib + Docetaxel (Phase 2, Double-blind) | 247 |
| Docetaxel + Placebo (Phase 2, Double-blind) | 215 |
Number of Participants With Adverse Events and Serious Adverse Events
"An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.~A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is Life-Threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.~Additional information about Adverse Events can be found in the Adverse Event Section." (NCT00077857)
Timeframe: First study drug intake until last study drug intake plus 28 days
| Intervention | Participants (Number) |
|---|
| Adverse Events | Serious Adverse Events |
|---|
| 1250 mg/m^2 Capecitabine + Docetaxel | 206 | 41 |
,| 825 mg/m^2 Capecitabine + Docetaxel | 234 | 53 |
Time to Overall Response
For patients with Best Overall Response being Complete Response (CR) or Partial Response (PR), time to response was measured as the time from randomization to the first time when the measurement criteria for CR or PR were met. The percentage of participants with overall response within the given time ranges in each of the categories: Weeks 1-6, 7-12, 13-18, 19-24, 25-30, 31-36, and 43-48 are reported. (NCT00077857)
Timeframe: Until PD or end of primary study treatment (up to 16 cycles) plus 28 days.
| Intervention | Percentage of participants (Number) |
|---|
| Week 1-6 | Week 7-12 | Week 13-18 | Week 19-24 | Week 25-30 | Week 31-36 | Week 43-48 |
|---|
| 1250 mg/m^2 Capecitabine + Docetaxel | 25 | 48 | 20 | 7 | 3 | 3 | 0 |
,| 825 mg/m^2 Capecitabine + Docetaxel | 30 | 30 | 17 | 7 | 1 | 2 | 1 |
Time to Progression of Disease or Death
Progression Free Survival was defined as the time from the date of randomization to the day of documented disease progression or death due to any cause. (NCT00077857)
Timeframe: Event driven (after 350 events). Median observation time was approximately 16 months.
| Intervention | Months (Median) |
|---|
| 1250 mg/m^2 Capecitabine + Docetaxel | 7.9 |
| 825 mg/m^2 Capecitabine + Docetaxel | 5.8 |
Percentage of Participants With Best Overall Response Being Complete Response (CR) or Partial Response (PR)
According to Response Evaluation Criteria in Solid Tumors (RECIST) criteria: CR is defined as the disappearance of all target lesions and PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the nadir sum LD. (NCT00077857)
Timeframe: Until Progressive Disease (PD) or end of primary study treatment (up to 16 cycles) plus 28 days.
| Intervention | Percentage of participants (Number) |
|---|
| 1250 mg/m^2 Capecitabine + Docetaxel | 45.1 |
| 825 mg/m^2 Capecitabine + Docetaxel | 37.4 |
Overall Survival
Overall Survival was measured as the time from the date of randomization to the date of death. (NCT00077857)
Timeframe: Throughout the study. Median observation time was approximately 16 months.
| Intervention | Months (Median) |
|---|
| 1250 mg/m^2 Capecitabine + Docetaxel | 16.4 |
| 825 mg/m^2 Capecitabine + Docetaxel | 15.1 |
Duration of Overall Response
Duration of overall response was measured from the time that measurement criteria were first met for Complete Response or Partial Response until the first date that progressive disease or death was documented. (NCT00077857)
Timeframe: Until PD or death. Median duration of response was approximately 7 months.
| Intervention | Months (Median) |
|---|
| 1250 mg/m^2 Capecitabine + Docetaxel | 6.9 |
| 825 mg/m^2 Capecitabine + Docetaxel | 6.9 |
Time to Treatment Failure
"The time to treatment failure was the time from the date of randomization to the first occurrence of any of the following events:~adverse events~insufficient therapeutic response (disease progression)~death~failure to return~refusing treatment/being unwilling to cooperate~withdrawing consent." (NCT00077857)
Timeframe: Until premature withdrawal or end of primary study treatment (up to 16 cycles).
| Intervention | Months (Median) |
|---|
| 1250 mg/m^2 Capecitabine + Docetaxel | 5.1 |
| 825 mg/m^2 Capecitabine + Docetaxel | 4.6 |
Disease-free Survival
Two-year rates are shown (Kaplan-Meier estimates). Disease-free survival is defined as the time from randomization to local, regional, or distant progression, second primary, or death (event) or last follow-up (censored). Response criteria as follows: No evidence of disease (NED): All patients must have no measurable tumor following surgery; Local-Regional Relapse: Recurrent cancer in the tumor bed and/or neck not clearly attributable to a second primary neoplasm; biopsy confirmation is necessary; Distant Relapse: Clear evidence of distant metastases (lung, bone, brain, etc.); Biopsy is recommended where possible. A solitary lung mass/nodule is considered a second primary neoplasm unless proven otherwise. (NCT00084318)
Timeframe: From randomization to 2 years
| Intervention | percentage of participants (Number) |
|---|
| RT + Cisplatin + Cetuximab | 57.3 |
| RT + Docetaxel + Cetuximab | 65.9 |
Frequency of Toxicity (Grade 5 and Acute Non-hematologic Grade 4)
Each regimen was monitored for excessive acute toxicity (defined as nonhematologic grade 4 toxicity within 90 days of the start of radiation or any grade 5 toxicity). The target rate was based on the observed rate from RTOG-9501/NCT00002670 of 15%. The unacceptable rate was >30%. [RTOG = Radiation Therapy Oncology Group] (NCT00084318)
Timeframe: From start of treatment to last follow-up. Analysis occurs at the time of the primary analysis.
| Intervention | percentage of participants (Number) |
|---|
| RT+Cisplatin+Cetuximab | 9.3 |
| RT+Docetaxel+Cetuximab | 12.3 |
Overall Survival
Two-year rates are shown (Kaplan-Meier estimates). Overall survival is defined as the time from randomization to death (event) or last follow-up (censored). (NCT00084318)
Timeframe: From randomization to 2 years
| Intervention | percentage of participants (Number) |
|---|
| RT + Cisplatin + Cetuximab | 68.8 |
| RT + Docetaxel + Cetuximab | 79.2 |
Frequency of Other Acute and Late Toxicity
Maximum grade toxicity that is definitely, probably, or possibly related to protocol treatment. (NCT00084318)
Timeframe: From start of treatment to last follow-up. Analysis occurs at the time of the primary endpoint analysis.
| Intervention | percentage of participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| RT+Cisplatin+Cetuximab | 1.0 | 10.3 | 74.2 | 14.4 | 0.0 |
,| RT+Docetaxel+Cetuximab | 0.0 | 9.4 | 73.6 | 16.0 | 0.9 |
Treatment Tolerance
Tolerability was defined as having received 90% of the radiation dose, 95% of the cetuximab loading dose, and at least 4 weeks of cetuximab and cisplatin or docetaxel at doses 95% of the protocol prescription. The percentage of patients determined to be tolerant of treatment are shown. (NCT00084318)
Timeframe: From start of treatment to end of treatment (protocol treatment lasts seven weeks).
| Intervention | percentage of participants (Number) |
|---|
| RT+Cisplatin+Cetuximab | 80.4 |
| RT+Docetaxel+Cetuximab | 84.9 |
Local-regional Control
Two-year rate is shown (cumulative incidence estimate). Local-regional failure is defined as the time from randomization to local-regional recurrence (event), death (competing risk), or last follow-up (censored). (NCT00084318)
Timeframe: From randomization to 2 years
| Intervention | percentage of participants (Number) |
|---|
| RT + Cisplatin + Cetuximab | 19.8 |
| RT + Docetaxel + Cetuximab | 18.9 |
Objective Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) 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 Rate defined as percentage of patients achieving a Best Response of either CR or PR. (NCT00086957)
Timeframe: After 3 cycles of treatment, up to 2 years.
| Intervention | percentage of participants (Number) |
|---|
| Dose Level 2 - Docetaxel 60 mg/m^2 | 64 |
Overall Survival
Estimated using the product-limit method of Kaplan and Meier. (NCT00086957)
Timeframe: Until death from any cause, up to 5 years.
| Intervention | Months (Median) |
|---|
| Dose Level 2 - Docetaxel 60 mg/m^2 | 43.2 |
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. 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 the appearance of new lesions. (NCT00086957)
Timeframe: Until disease progression, up to 5 years.
| Intervention | Months (Median) |
|---|
| Dose Level 2 - Docetaxel 60 mg/m^2 | 12.7 |
Number of Participants With at Least One Dose Limiting Toxicity in Phase I
Dose Limiting Toxicity (DLT) defined as any treatment-related grade 3 or greater except for hematological toxicities which must be grade 4. Interstitial Lung Disease (ILD) related to treatment should be considered as a DLT regardless of the grade. (NCT00086957)
Timeframe: 4 weeks from start of treatment, up to 2 years
| Intervention | participants with DLTs (Number) |
|---|
| Phase I: Dose Level 1 - Docetaxel 75 mg/m^2 | 2 |
| Phase I: Dose Level 2 - Docetaxel 60 mg/m^2 | 0 |
Recommended Phase II Dose
The maximum tolerated dose (MTD): subjects received gefitinib 250 mg orally daily, trastuzumab 6 mg/kg intravenously every 3 weeks (after an initial dose of 8 mg/kg with cycle 1), and docetaxel 75 mg/m^2 intravenously every 3 weeks. This was to serve as the phase II dose if no dose-limiting toxicities (DLTs) occurred in the first three subjects. If one DLT occurred in the first three subjects, another three subjects where to be enrolled at this dose, whereas if two DLTs occurred in the first three subjects, the docetaxel dose was to be decreased to 60 mg/m^2. The study would then be continued only if no more than one patient had a DLT at this dose. Once the dose of docetaxel was established, all further subjects were to be treated at the phase II MTD dose. (NCT00086957)
Timeframe: 4 weeks from start of treatment, up to 2 years
| Intervention | mg/m^2 (Number) |
|---|
| Phase I | 60 |
Overall Survival
Overall survival is defined as time from registration to death from any cause. All eligible and treated patients were included in the analysis. (NCT00088907)
Timeframe: assessed every 3 months if patient is < 2 years from study entry then every 6 months if patient is 2-5 years from study entry. No specific requirements if patient is more than 5 years from study entry.
| Intervention | months (Median) |
|---|
| Arm I (Docetaxel and Placebo) | 5.98 |
| Arm II (Docetaxel and Gefitinib) | 7.33 |
Overall 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.~Tumor measurements may be made using physical examination, CT scans or MRI scans. While on protocol treatment, tumor measurement by physical examination to be done every 4 weeks, and tumor measurement by CT/MRI scans to be done every 8 weeks (every 2 treatment cycles).~All eligible and treated patients were included in the analysis." (NCT00088907)
Timeframe: assessed every 3 months if patient is < 2 years from study entry then every 6 months if patient is 2-5 years from study entry. No specific requirements if patient is more than 5 years from study entry.
| Intervention | percentage of participants (Number) |
|---|
| Arm I (Docetaxel and Placebo) | 4.3 |
| Arm II (Docetaxel and Gefitinib) | 9.8 |
Time to Progression
"Time to progression is defined as time from registration to disease progression. 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 .~Tumor measurements may be made using physical examination, CT scans or MRI scans. While on protocol treatment, tumor measurement by physical examination to be done every 4 weeks, and tumor measurement by CT/MRI scans to be done every 8 weeks (every 2 treatment cycles).~All eligible and treated patients were included in the analysis." (NCT00088907)
Timeframe: assessed every 3 months if patient is < 2 years from study entry then every 6 months if patient is 2-5 years from study entry. No specific requirements if patient is more than 5 years from study entry.
| Intervention | months (Median) |
|---|
| Arm I (Docetaxel and Placebo) | 2.14 |
| Arm II (Docetaxel and Gefitinib) | 3.55 |
Disease Free Survival Including Any New Cancer as Event [Number of Events]
Number of patients with/without recurrence of breast cancer, any new cancer, or death due to any cause. (NCT00089479)
Timeframe: Time from the date of randomization until the date of first event, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years.
| Intervention | participants (Number) |
|---|
| Patients with event | Patients without events |
|---|
| AC Then T | 200 | 1104 |
,| AC Then XT | 177 | 1130 |
Disease Free Survival [Number of Events]
Number of patients with/without recurrence of breast cancer, or death due to any cause. (NCT00089479)
Timeframe: Time from the date of randomization until the date of first event, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years.
| Intervention | participants (Number) |
|---|
| Patients with event | Patients without events |
|---|
| AC Then T | 164 | 1140 |
,| AC Then XT | 140 | 1167 |
Breast Cancer Free Survival [Number of Events]
Number of patients with/without recurrence of breast cancer, new primary breast cancer, or death related to the chemotherapy administered or due to breast cancer. (NCT00089479)
Timeframe: Time from the date of randomization to event, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years .
| Intervention | participants (Number) |
|---|
| Patients with event | Patients without events |
|---|
| AC Then T | 158 | 1146 |
,| AC Then XT | 144 | 1163 |
Overall Survival [Time to Event]
Overall survival was measured as the time from the date of randomization to the date of death. Patients still alive at the time of the analysis were censored using the date they were last known to be alive. (NCT00089479)
Timeframe: Time from the date of randomization to the date of death, or date last known to be alive. Patients were followed for an average of 5 years.
| Intervention | months (Median) |
|---|
| AC Then T | NA |
| AC Then XT | NA |
Disease Free Survival Including New Primary Breast Cancer as Event [Time to Event
Time from the date of randomization until the date of first event (recurrence of breast cancer, new primary breast cancer, or death due to any cause). Patients without event at the time of the analysis were censored using the date they were last known to be recurrent disease free. (NCT00089479)
Timeframe: Time from the date of randomization until the date of first event, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years.
| Intervention | months (Median) |
|---|
| AC Then T | NA |
| AC Then XT | NA |
Disease Free Survival Including Any New Cancer as Event [Time to Event]
Time from the date of randomization until the date of first event (recurrence of breast cancer, any new cancer, or death due to any cause). Patients without event at the time of the analysis were censored using the date they were last known to be recurrent disease free. (NCT00089479)
Timeframe: Time from the date of randomization until the date of first event, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years.
| Intervention | months (Median) |
|---|
| AC Then T | NA |
| AC Then XT | NA |
Breast Cancer Free Survival [Time to Event]
Breast cancer-free survival was measured as time from the date of randomization to the date of recurrence of breast cancer, new primary breast cancer, or death related to the chemotherapy administered or due to breast cancer. Patients without event at the time of the analysis were censored using the date they were last known to be recurrent disease free. (NCT00089479)
Timeframe: Time from the date of randomization to death, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years.
| Intervention | months (Median) |
|---|
| AC Then T | NA |
| AC Then XT | NA |
Disease Free Survival [Time to Event]
Disease free survival was measured as the time from the date of randomization until the date of first event (recurrence of breast cancer, or death due to any cause). Patients without event at the time of the analysis were censored using the date they were last known to be recurrent disease free. (NCT00089479)
Timeframe: Time from the date of randomization until the date of first event, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years.
| Intervention | months (Median) |
|---|
| AC Then T | NA |
| AC Then XT | NA |
Overall Survival [Number of Events]
Number of patients who died/were alive. (NCT00089479)
Timeframe: Time from the date of randomization to the date of death, or date last known to be alive. Patients were followed for an average of 5 years.
| Intervention | participants (Number) |
|---|
| Patients with event | Patients without events |
|---|
| AC Then T | 108 | 1196 |
,| AC Then XT | 75 | 1232 |
Disease Free Survival Including New Primary Breast Cancer as Event [Number of Events]
Number of patients with/without recurrence of breast cancer, new primary breast cancer, or death due to any cause. (NCT00089479)
Timeframe: Time from the date of randomization until the date of first event, or date last known to be event free if no event was reported. Patients were followed for an average of 5 years.
| Intervention | participants (Number) |
|---|
| Patients with event | Patients without events |
|---|
| AC Then T | 169 | 1135 |
,| AC Then XT | 154 | 1153 |
Number of Participants Who Died After a Follow Up of 34 Months Following Treatment
From on study date to date of death at 34 months. (NCT00089609)
Timeframe: 34 months
| Intervention | Participants (Count of Participants) |
|---|
| Main Cohort - Prostate Cancer | 38 |
Number of Participants With a Significant Increase in Circulating Apoptotic Endothelial Cell (CAEC) Level
"The assay utilized has no standard curve. Categorizing patients with ≥ 75% PSA decline in one group and < PSA decline in another group, every patient is their own control with comparison of CAEC at baseline vs. 6 weeks (after two cycles of treatment). Blood is drawn from the patient and a million viable mononuclear cells are counted and then it is determined how many CAECs are in the specimen. The cell count is then compared from baseline to post 2 cycles of treatment. Thus, significant increase is dependent upon this comparison and varies between patients." (NCT00089609)
Timeframe: Baseline and at 6 weeks (after two cycles of treatment)
| Intervention | Participants (Count of Participants) |
|---|
| Main Cohort - Particpants With ≥75% PSA Decline | 14 |
| Main Cohort - Particpants With <75% PSA Decline | 0 |
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. (NCT00089609)
Timeframe: 37 months
| Intervention | Participants (Count of Participants) |
|---|
| Main Cohort - Prostate Cancer | 60 |
| Expansion Cohort - Prostate Cancer | 13 |
Time to Progression Using Bubley Criteria
Time to disease progression was based on the Prostate-Specific Antigen (PSA) Working Group 1 Criteria (Bubley Criteria) and standard Response Evaluation Criteria in Solid Tumors (RECIST) for measurable disease. Per the criteria, investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. (NCT00089609)
Timeframe: up to 40 months
| Intervention | Months (Median) |
|---|
| Main Cohort - Prostate Cancer | 18.3 |
Number of Participants Who Had a Prostate-specific Antigen (PSA) Response
PSA response was assessed by the PSA Consensus Criteria. PSA decline is defined as a decline in PSA of at least 50% with no other evidence of disease progression. (NCT00089609)
Timeframe: 21.6 months
| Intervention | Participants (Count of Participants) |
|---|
| Main Cohort - Prostate Cancer | 52 |
Disease Progression by Clinical and Radiographic Criteria Without the Use of Prostate-Specific Antigen (PSA)
Clinical and radiographic response was measured by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease 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. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking s reference the smallest sum LD since the treatment started. Progressive disease (PD) is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded or the appearance of one or more new lesions. (NCT00089609)
Timeframe: up to 34 months
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) |
|---|
| Main Cohort - Prostate Cancer | 2 | 19 | 11 | 1 |
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
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Cycle 1 | Cycle 2 | Cycle 3 | Cycle 4 | Cycle 5 | Cycle 6 | End of Study |
|---|
| Arm 1 | 76.3 | 65.1 | 72.7 | 69.4 | 70.8 | 69.3 | 74.3 | 71.4 |
,| Arm 2 | 76.6 | 73.3 | 75.3 | 75.6 | 76.0 | 74.0 | 81.2 | 78.0 |
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
| Intervention | months (Median) |
|---|
| Arm 1 | 13.7 |
| Arm 2 | 8.4 |
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
| Intervention | months (Median) |
|---|
| Arm 1 | 20 |
| Arm 2 | 15.8 |
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
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 55.4 |
| Arm 2 | 43.3 |
Time to Progression
Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first. (NCT00091442)
Timeframe: From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled
| Intervention | Months (Median) |
|---|
| Docetaxel | 7.0 |
| DOXIL+Docetaxel | 9.8 |
Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR)
Number of participants in the evaluable population who achieved a CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: Disappearance of all target lesions and PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Response was assessed by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI). (NCT00091442)
Timeframe: Up to 30 to 42 days after last dose of study medication
| Intervention | Participants (Number) |
|---|
| Docetaxel | 95 |
| DOXIL+Docetaxel | 129 |
Overall Survival
Time interval in months between the date of randomization and the participant's death from any cause. (NCT00091442)
Timeframe: From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled
| Intervention | Months (Median) |
|---|
| Docetaxel | 20.7 |
| DOXIL+Docetaxel | 20.4 |
Disease-free Survival: Any Recurrence, Contralateral Breast Cancer, Second Primary Cancer, Death From Any Cause Prior to Recurrence or Second Primary Cancer
The percentage of patients alive and cancer-free. (NCT00093795)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Group 1: TAC X 6 | 80.1 |
| Group 2: AC X 4 Then P X 4 | 82.2 |
| Group 3: AC X 4 Then PG X 4 | 80.6 |
Distant Recurrence-free Interval: the Time to Distant Disease Recurrence Only
Percentage of patients distant recurrence-free (no distant disease recurrence only) (NCT00093795)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Group 1: TAC X 6 | 86.6 |
| Group 2: AC X 4 Then P X 4 | 87.4 |
| Group 3: AC X 4 Then PG X 4 | 86.6 |
Recurrence-free Interval: Time to First Local, Regional, or Distant Recurrence
Percentage of patients recurrence-free (no first local, regional, or distant recurrence) (NCT00093795)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Group 1: TAC X 6 | 85.1 |
| Group 2: AC X 4 Then P X 4 | 86.2 |
| Group 3: AC X 4 Then PG X 4 | 84.8 |
Overall Survival
Percentage of participants alive at 5 years (NCT00093795)
Timeframe: 5 years
| Intervention | percentage of patients alive (Number) |
|---|
| Group 1: TAC X 6 | 89.6 |
| Group 2: AC X 4 Then P X 4 | 89.1 |
| Group 3: AC X 4 Then PG X 4 | 90.8 |
Toxicity
Percentage of patients who ever experienced grade 2 or higher toxicities. (NCT00093795)
Timeframe: 30 days after the last dose of study therapy (about 7 months after study entry)
| Intervention | percentage of patients (Number) |
|---|
| Group 1: TAC X 6 | 82.7 |
| Group 2: AC X 4 Then P X 4 | 87.5 |
| Group 3: AC X 4 Then PG X 4 | 88.4 |
Proportion of Randomized Participants With the Best Overall Response (OR) of Partial Response (PR) or Complete Response (CR) (Overall Response Rate [ORR])
The best overall response rate (ORR) was the proportion of randomized participants with a best OR of CR or PR, according to modified World Health Organization (WHO) guidelines. It was calculated as the total number of participants with CR or PR divided by the total number of participants treated in that arm. Participants with no post-baseline evaluation were considered as non-responders. The tumor response was assessed by the independent review committee (IRC) in the Pemetrexed group and by the investigator in the Docetaxel group. (NCT00095199)
Timeframe: Randomization until progression of disease or death from any cause up to 59.6 months
| Intervention | proportion of participants (Number) |
|---|
| Cetuximab & Pemetrexed | 0.066 |
| Pemetrexed | 0.043 |
| Cetuximab & Docetaxel | 0.078 |
| Docetaxel | 0.066 |
Duration of Overall Response (OR)
The duration of response, in participants with best OR of complete response (CR) or partial response (PR), was measured from the date criteria are met for CR/PR (not confirmation date, whichever was first recorded), until the first occurrence date that the criteria of progressive disease (PD) was met, or death. Participants who were alive and without progression were censored at the date of their last independent review committee (IRC) tumor assessment. The tumor response and progression were assessed by the IRC in the Pemetrexed group and by the investigator in the Docetaxel group. (NCT00095199)
Timeframe: Time of first occurrence of either (PR) or (CR) to the first date of progressive disease or death up to 32.5 months
| Intervention | months (Median) |
|---|
| Cetuximab & Pemetrexed | 4.17 |
| Pemetrexed | 6.93 |
| Cetuximab & Docetaxel | 5.36 |
| Docetaxel | 5.39 |
Time to Symptomatic Progression
The FACT-LCS (see description in Outcome measure 5) inventories problems specific to lung cancer symptoms. Using this Scale, Symptom progression = a ≥ 2 point decrease from baseline in LCS score maintained for 2 consecutive assessments ≥3 weeks, and <5 weeks, apart. The symptom progression date = the first of 2 consecutive assessments with a ≥2 point decline. Time to symptomatic progression = the time from randomization to the symptom progression date. For participants with no symptom progression, time to symptomatic progression was censored the date of last symptom assessment. (NCT00095199)
Timeframe: Randomization until symptomatic progression up to 48.3 months
| Intervention | months (Median) |
|---|
| Cetuximab & Pemetrexed | NA |
| Pemetrexed | NA |
| Cetuximab & Docetaxel | NA |
| Docetaxel | NA |
Overall Survival (OS)
OS was defined as the time from randomization to death. Participants without a date of death were censored on the last date participants were known to be alive, or lost to follow-up. (NCT00095199)
Timeframe: Randomization to the date of death from any cause up to 72.8 months
| Intervention | months (Median) |
|---|
| Cetuximab & Pemetrexed | 6.93 |
| Pemetrexed | 7.79 |
| Cetuximab & Docetaxel | 5.75 |
| Docetaxel | 8.15 |
Percentage of Participants With Symptomatic Response (Symptom Response Rates) Using the Lung Cancer Subscale (LCS) Scores of Functional Assessment of Cancer Therapy for Participants With Lung Cancer (FACT-L)
The FACT-LCS is a set of 7 questions to inventory problems specific to lung cancer symptoms. Participants rate each item on a 5-point Likert-type scale from 0 (not at all) to 4 (very much). Scores range from 0-28 and higher score indicates fewer symptoms. Symptom response (improvement) was defined as ≥2 point increase from baseline in the 7-item LCS score that was maintained for 2 consecutive assessments at least 3 weeks, and not >5 weeks apart for participants, whose baseline LCS score was ≤26. Symptom response rate was the percentage of participants with symptomatic response. (NCT00095199)
Timeframe: At baseline, every 3 weeks and 30 days after end of therapy up to 50 months
| Intervention | percentage of participants (Number) |
|---|
| Cetuximab & Pemetrexed | 17.1 |
| Pemetrexed | 22.9 |
| Cetuximab & Docetaxel | 17.3 |
| Docetaxel | 13.5 |
Progression Free Survival (PFS)
PFS was defined as the time from randomization until the date of progressive disease (PD) or death from any cause. Participants who were alive and without progression were censored at the date of their last tumor assessment. PFS was assessed by the independent review committee (IRC) in the Pemetrexed group (Cetuximab & Pemetrexed versus Pemetrexed) and by the investigator in the Docetaxel group (Cetuximab & Docetaxel versus Docetaxel). (NCT00095199)
Timeframe: Randomization to progression of disease or death due to any cause up to 59.6 months
| Intervention | months (Median) |
|---|
| Cetuximab & Pemetrexed | 2.89 |
| Pemetrexed | 2.76 |
| Cetuximab & Docetaxel | 2.37 |
| Docetaxel | 1.54 |
Proportion of Randomized Participants With Best Overall Response (OR) of Partial Response (PR), Complete Response (CR), or Stable Disease (SD)
The disease control rate (DCR) was the proportion of randomized participants with a best OR of CR, PR or SD according to modified World Health Organization (WHO) guidelines. It was calculated as the total number of participants with CR, PR or SD divided by the total number of participants randomized in that arm. The tumor response was assessed by the independent review committee (IRC) in the Pemetrexed group and by the investigator in the Docetaxel group. (NCT00095199)
Timeframe: Randomization to progression of disease or death due to any cause up to 59.6 months
| Intervention | proportion of participants (Number) |
|---|
| Cetuximab & Pemetrexed | 0.522 |
| Pemetrexed | 0.480 |
| Cetuximab & Docetaxel | 0.335 |
| Docetaxel | 0.253 |
Number of Participants With Common Toxicity Criteria (CTC) Grade 3 or 4 Toxicities
National Cancer Institutes-Common Toxicity Criteria version 3.0 was used by investigators to assess participant toxicities. Mapping of investigator verbatim terms to CTCAE terms was done by the sponsor/designee using CTCAE v4.0. Participants reported had grade 3 or 4 toxicities (or both potentially). Grade 3 AEs: severe or medically significant but not immediately life-threatening;hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living. Grade 4 AEs: life-threatening consequences; urgent intervention indicated. (NCT00095199)
Timeframe: Time from first dose to 30 days after last dose of study therapy up to 28.3 months for Cetuximab & Pemetrexed (versus Pemetrexed alone) and up to 54.3 months for Cetuximab + Docetaxel (versus Docetaxel alone)
| Intervention | participants (Number) |
|---|
| Cetuximab & Pemetrexed | 179 |
| Pemetrexed | 143 |
| Cetuximab + Docetaxel | 112 |
| Docetaxel | 97 |
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
| Intervention | percent of patients (Number) |
|---|
| Arm I | 73 |
| Arm II | 78 |
Proportion of Participants Who Experience (Maximum) Grade 3 or Higher Toxicities
"The National Cancer Institute (NCI) Criteria for Adverse Events(CTCAE) Version 3.0 was used to evaluate toxicity. These events were considered at least possibly related to treatment.~Grade 1: mild; Grade 2: moderate; Grade 3: Severe; Grade 4: Life Threatening; Grade 5: Death" (NCT00110214)
Timeframe: During treatment (up to 2 years)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel + Placebo | 56.2 |
| Docetaxel + Bevacizumab | 75.4 |
Proportion of Participants Who Experienced at Least a 50% Post-therapy PSA (Prostate-Specific Antigen) Decline
PSA decline will be reported on all patients and will be defined as a decrease in PSA value by >= 50% for two successive evaluations at least 4 weeks apart. The reference PSA value for these declines should be measured within 2 weeks before starting therapy. (NCT00110214)
Timeframe: Duration of study (up to 5 years)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel + Placebo | 57.9 |
| Docetaxel + Bevacizumab | 69.5 |
Overall Survival
Overall Survival (OS) was measured from the date of randomization to date of death due to any cause. OS was estimated using the Kaplan Meier method. (NCT00110214)
Timeframe: Duration of study (up to 5 years)
| Intervention | months (Median) |
|---|
| Docetaxel + Placebo | 21.5 |
| Docetaxel + Bevacizumab | 22.6 |
Progression-free Survival (PFS)
"PFS was defined as the data of randomization to date of progression or death due to any cause, whichever occurs first. PFS was estimated using the Kaplan Meier method.~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" (NCT00110214)
Timeframe: Duration of study (up to 5 years)
| Intervention | months (Median) |
|---|
| Docetaxel + Placebo | 7.5 |
| Docetaxel + Bevacizumab | 9.9 |
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).
| Intervention | Participants (Number) |
|---|
| Neutropenia | Leukopenia | Thrombocytopenia | Anemia |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 198 | 139 | 33 | 17 |
,| Taxane+Carboplatin (T/C) | 177 | 97 | 29 | 15 |
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).
| Intervention | Participants (Number) |
|---|
| Hyperglycemia (non-fasting) | Hypomagnesemia | Hyponatremia | Low albumin |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 33 | 26 | 25 | 17 |
,| Taxane+Carboplatin (T/C) | 36 | 2 | 21 | 9 |
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).
| Intervention | Participants (Number) |
|---|
| Death | Serious adverse events | Adverse events |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 38 | 183 | 324 |
,| Taxane+Carboplatin (T/C) | 27 | 121 | 320 |
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).
| Intervention | participants (Number) |
|---|
| Cetuximab | Taxane | Carboplatin |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 100 | 80 | 78 |
,| Taxane+Carboplatin (T/C) | 0 | 54 | 52 |
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).
| Intervention | Participants (Number) |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 107 |
| Taxane+Carboplatin (T/C) | 92 |
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).
| Intervention | Participants (Number) |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 230 |
| Taxane+Carboplatin (T/C) | 212 |
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).
| Intervention | Participants (Number) |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 87 |
| Taxane+Carboplatin (T/C) | 58 |
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).
| Intervention | Participants (Number) |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 45 |
| Taxane+Carboplatin (T/C) | 18 |
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).
| Intervention | Participants (Number) |
|---|
| Cetuximab+Taxane+Carboplatin (C/T/C) | 58 |
| Taxane+Carboplatin (T/C) | 25 |
Incidence of Adverse Effects That Are Grade 3 or Greater as Assessed by Common Terminology Criteria for Adverse Events Version 3.0
Count of participants with Toxicities maximum grade greater than or equal to grade 3 (NCT00114218)
Timeframe: Assessed every 28 days (28 days=1 cycle) while on study treatment, 30 days after the last cycle of treatment, and up to 5 years in follow-up
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Gemcitabine Hydrochloride, Docetaxel) | 18 |
Percentage of Patients With Objective Tumor Response Rate (Either Complete Response (CR) or Partial Response (PR) Using RECIST Version 1.0
RECIST 1.0 defines complete response as the disappearance of all target lesions and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart. Partial response is defined as 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 non-target lesions and no new lesions. Documentation by two disease assessments at least 4 weeks apart is required. In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% decrease in the LD is required. These patients will have their response classified according to the definitions stated above. Complete and partial responses are included in the objective tumor response rate. (NCT00114218)
Timeframe: CT scan or MRI if used to follow lesions for measurable disease every other cycle for the first 6 months; every 6 months thereafter until disease progression for up to 5 years.
| Intervention | Percentage of participants (Number) |
|---|
| Treatment (Gemcitabine Hydrochloride, Docetaxel) | 8 |
Number of Participants With Late Adverse Events, Any Grade and Attribution
Late adverse events will be focused on GU/GI including Urinary/Fecal Incontinence, Hematuria, Diarrhea, Rectal Bleeding and other. (NCT00116142)
Timeframe: Every 6 months post radiation therapy for 5 years (+/-90 days), then annually, up to 13.9 years from randomization
| Intervention | Participants (Count of Participants) |
|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 128 |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 140 |
Number of Participants With Acute Adverse Events
Adverse acute events were reported via the clinical database only for toxicities considered reportable via the SAE mechanism (those of grade 2 and grade 3 events that are unexpected and possibly, probably, or definitely related/associated with treatment; or all grade 4 and grade 5 events). Common Toxicity Criteria Volume 3.0 (CTCAE) is used for this study. (NCT00116142)
Timeframe: During study treatment or within 30 days of the last dose of study, up to 7.2 months from randomization
| Intervention | Participants (Count of Participants) |
|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 18 |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 46 |
10-Year Restricted Mean Survival Time for Overall Survival
Overall survival (OS) was measured from the date of random assignment to death from any cause, censored at the date of last follow-up in surviving patients. The 10-Year Restricted Mean Survival Time was calculated as the area under the Kaplan Meier plot for OS, from randomization to 10-years follow-up (NCT00116142)
Timeframe: Following the end of RT patients were seen for follow up every 6 months for 5 years and annually thereafter, 10 years.
| Intervention | years (Mean) |
|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 8.82 |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 9.11 |
10-year Biochemical Recurrence (PSA Failure)
"Time to biochemical recurrence was defined as the time from date of random assignment to the earliest of PSA failure or initiation of salvage therapy, or censored at the date of last disease assessment for those without PSA failure. PSA failure was defined according to the 2006 RTOG-ASTRO Phoenix definition (i.e., A PSA rise by 2 ng/mL or more above the nadir).~10-year biochemical recurrence rate was estimated from a competing risk model where non-prostate cancer death was counted as competing risk." (NCT00116142)
Timeframe: PSA was measured following the end of RT, then every 6 months for 5 years and annually thereafter, 10 years
| Intervention | percentage of subjects (Number) |
|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 48 |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 54 |
10-year Prostate Cancer Mortality
Measured from the date of random assignment to date of death from prostate cancer, or censored at the date of last follow-up in surviving patients. Patients who died due to other reasons were counted as competing risk in a competing risk model. (NCT00116142)
Timeframe: Following the end of RT patients were seen for follow up every 6 months for 5 years and annually thereafter, 10 years.
| Intervention | percentage of subjects (Number) |
|---|
| Arm1: Androgen Suppression Therapy + Radiation Therapy | 11 |
| Arm2: Docetaxel + Androgen Suppression Therapy + Radiation Therapy | 15 |
Quality of Life (McMaster)
McMaster RT Questionnaire (4-28 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to 1 year (1 year-pre)
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -3.29 |
| Chemoradiotherapy | -6.00 |
Quality of Life (McMaster)
McMaster RT Questionnaire (4-28 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to post-CRT (post-pre). This corresponds to week 16 in the induction arm and week 10 in the CRT alone arm.
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -9.72 |
| Chemoradiotherapy | -9.79 |
Quality of Life (Normalcy of Diet)
Performance Status Score (0-100 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to post-CRT (post-pre). This corresponds to week 16 in the induction arm and week 10 in the CRT alone arm.
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -54.00 |
| Chemoradiotherapy | -41.51 |
Quality of Life (Speech)
Performance Status Score (0-100 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to post-CRT (post-pre). This corresponds to week 16 in the induction arm and week 10 in the CRT alone arm.
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -10.67 |
| Chemoradiotherapy | -7.35 |
Quality of Life (FACT H&N)
FACT Hand-and-neck subscale(b) (0-40 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to post-CRT (post-pre). This corresponds to week 16 in the induction arm and week 10 in the CRT alone arm.
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -11.41 |
| Chemoradiotherapy | -12.34 |
Overall Survival: Time From Randomization to Death From Any Cause
Survival rates over 6 years. (NCT00117572)
Timeframe: Up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Induction Plus Chemoradiotherapy | 74.9 |
| Chemoradiotherapy | 72.8 |
Recurrence Free Survival: Time From Randomization to Local/Regional/Distant Recurrence or Death From Any Cause
Recurrence-free survival rates over 6 years. Recurrence-free survival is time from randomization to local, regional, or distant recurrence or death from any cause (NCT00117572)
Timeframe: Up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Induction Plus Chemoradiotherapy | 68.6 |
| Chemoradiotherapy | 58.6 |
Quality of Life (Normalcy of Diet)
Performance Status Score (0-100 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to 1 year (1 year-pre)
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -10.22 |
| Chemoradiotherapy | -8.89 |
Distant Failure-free Survival (DFFS): Time From Randomization to Distant Recurrence or Death From Any Cause
DFFS rates over 6 years. DFFS is time from randomization to distant recurrence or death from any cause (NCT00117572)
Timeframe: Up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Induction Plus Chemoradiotherapy | 69.3 |
| Chemoradiotherapy | 63.8 |
Failure Pattern (Distant Recurrence)
Percentage of patients with distant recurrence (NCT00117572)
Timeframe: Up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Induction Plus Chemoradiotherapy | 13.8 |
| Chemoradiotherapy | 21.5 |
Failure Pattern (Local/Regional Recurrence)
Percentage of patients with local/regional recurrence (NCT00117572)
Timeframe: Up to 6 years
| Intervention | percentage of participants (Number) |
|---|
| Induction Plus Chemoradiotherapy | 10.1 |
| Chemoradiotherapy | 12.6 |
Quality of Life (Speech)
Performance Status Score (0-100 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to 1 year (1 year-pre)
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -1.70 |
| Chemoradiotherapy | -3.41 |
Quality of Life (FACT H&N)
FACT Hand-and-neck subscale(b) (0-40 point scale with negative numbers indicating worsening of function) (NCT00117572)
Timeframe: Change from baseline to 1 year (1 year-pre)
| Intervention | units on a scale (Mean) |
|---|
| Induction Plus Chemoradiotherapy | -7.60 |
| Chemoradiotherapy | -7.34 |
Overall Tumor Response Rate
"Patients experiencing 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., or similar definition that is accurate and appropriate." (NCT00118131)
Timeframe: 7 years
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel and Cisplatin | 21 |
1-year Survival Rate
(NCT00118131)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel and Cisplatin | 38 |
Time to Progressive 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. (NCT00118131)
Timeframe: 8 years
| Intervention | months (Median) |
|---|
| Docetaxel and Cisplatin | 3.38 |
Disease Free Survival in Hormonal Receptor Positive and HER2 Negative Subgroup
"Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally.~Disease-Free Survival (DFS) is 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 or death from any cause whichever occurs first." (NCT00121992)
Timeframe: 10 year
| Intervention | events (Number) |
|---|
| Arm A: FAC | 50 |
| Arm B: TAC | 37 |
Disease-free Survival (DFS) Events
DFS is calculated from the date of randomization until the first date of recurrence local, regional or distant, second primary tumor or death. (NCT00121992)
Timeframe: 10 years
| Intervention | events (Number) |
|---|
| Arm A: FAC | 127 |
| Arm B: TAC | 112 |
Number of Disease Free Survival Events in Hormone-receptor Positive and Human Epidermal Growth Factor Receptor 2 (HER2) Positive Status Subgroup
Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is 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 or death from any cause whichever occurs first. (NCT00121992)
Timeframe: 10 year
| Intervention | events (Number) |
|---|
| Arm A: FAC | 6 |
| Arm B: TAC | 6 |
The Number of Participants Who Experienced Adverse Events (AE)
Safety was assessed by standard clinical and laboratory tests (haematology, serum chemistry). AE grade were defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 1.0. (NCT00121992)
Timeframe: Through study treatment, and average of 4 months
| Intervention | participants (Number) |
|---|
| Number patients with One AE | One G3-4 or severe treatment-emergent AE | One serious treatment-emergent AE | One serious G3-4 treatment-emergent AE | Number of patients discontinued due to AE | Number patients death due to AE |
|---|
| Arm A: FAC | 519 | 88 | 22 | 10 | 4 | 0 |
,| Arm B: TAC | 532 | 151 | 119 | 55 | 25 | 1 |
Overall Survival (OS)
"OS was determined from the date of randomization until the date of death for any reason.~OS is calculated from the date of randomization up to the first date of death by any cause." (NCT00121992)
Timeframe: 10 years
| Intervention | Participants with mortality event (Number) |
|---|
| Arm A: FAC | 57 |
| Arm B: TAC | 53 |
Disease Free Survival in Hormonal Receptor Negative and HER2 Negative Subgroup
Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. Disease-Free Survival (DFS) is 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 or death from any cause whichever occurs first. (NCT00121992)
Timeframe: 10 year
| Intervention | events (Number) |
|---|
| Arm A: FAC | 29 |
| Arm B: TAC | 28 |
Disease Free Survival in Hormonal Receptor Negative and HER2 Positive Subgroup
Hormone-receptor status and HER2 receptor status was analysed in Paraffin-embedded tumor samples obtained at the time of surgery, and were processed centrally. (NCT00121992)
Timeframe: 10 year
| Intervention | events (Number) |
|---|
| Arm A: FAC | 6 |
| Arm B: TAC | 5 |
Best Score During Study for Global Health Status Scale
"The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) was used.~Questionnaires were self-administered to patients during the 14 days prior to randomisation baseline, at six prospective time points corresponding to chemotherapy cycles, with the time window related to each chemotherapy cycle defined as the period between the day following the first chemotherapy dose of the corresponding cycle and the day of the first dose of the following cycle, and then at 44, 68 and 120 weeks of the study.~The Global Health Status Scale has been used, which is calculated with questions 29 and 30 from the EORTC QLQ-C30. From this scale, the best score is the highest score observed during study (of all the questionnaires completed by patient). In this scale, scores range from 0 to 100 and a high score represents a high level of functioning or HRQoL." (NCT00121992)
Timeframe: 120 weeks
| Intervention | score on a scale (Mean) |
|---|
| Arm A: FAC | 79.30 |
| Arm B: TAC | 77.78 |
Percentage of Participants With Complete Pathological Response in the Primary Breast Tumor at the Time of Definitive Surgery
Pathological complete response was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. (NCT00127933)
Timeframe: at the time of definitive surgery; after four 3-week cycles (3-4 months)
| Intervention | percentage of participants (Number) |
|---|
| HER2-Neu Negative | 9.9 |
| HER2-Neu Positive | 35.7 |
Participants With Overall Survival
Overall survival was defined as the time from date of start of study treatment to the date of death, regardless of the cause of death. Patients who were alive at the time of the analysis were censored at the date of the last follow-up assessment. Patients without follow-up assessment were censored at the day of the last dose. Patients with no post-baseline information were censored at the start of study treatment. (NCT00127933)
Timeframe: 22 - 1191 days
| Intervention | participants (Number) |
|---|
| HER2-Neu Negative | 118 |
| HER2-Neu Positive | 32 |
Participants With Disease-Free Survival
Disease-free survival was defined as the time from date of surgery to date of first evidence of cancer recurrence in the breast (ie, local or distant recurrence or contra lateral disease) or death from any cause, whichever came first. Patients who were alive or withdrawn from the study and had no evidence of disease recurrence and for whom there was CRF evidence that evaluations had been made were censored at the date of the last clinical follow-up assessment when the patient was known to be disease free. (NCT00127933)
Timeframe: 30 - 1102 days
| Intervention | participants (Number) |
|---|
| HER2-Neu Negative | 92 |
| HER2-Neu Positive | 25 |
Percentage of Participants Assessed for Pathological Complete Response (pCR) Plus Near Complete (npCR) in Primary Breast Tumor at Time of Definitive Surgery
Pathological complete response was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. Near pCR (npCR) was defined as the presence of invasive tumor cells with a size of 5 mm or less in aggregate in the tissue specimen removed from the breast after 4 cycles of preoperative treatment. Only pathological assessments occurring prior to the first date of adjuvant treatment were included in the analysis of pCR rate. (NCT00127933)
Timeframe: at the time of definitive surgery; after four 3-week cycles (3-4 months)
| Intervention | percentage of participants (Number) |
|---|
| HER2-Neu Negative | 15.8 |
| HER2-Neu Positive | 50.0 |
Percentage of Participants With Local Recurrence
Local recurrence was defined as evidence of recurrent carcinoma in the same breast where it was diagnosed initially before preoperative treatment. (NCT00127933)
Timeframe: 30 - 1102 days
| Intervention | percentage of participants (Number) |
|---|
| HER2-Neu Negative | 3.1 |
| HER2-Neu Positive | 3.7 |
Percentage of Participants With Overall Clinical Response (Complete Response (CR) Plus Partial Response (PR))
The best overall response in an individual patient, according to RECIST, during preoperative treatment was the best response recorded from the start of study treatment until disease progression/recurrence (taking as reference for PD the smallest measurements recorded since the baseline assessment) or completion of preoperative treatment. Patients with CR or PR were considered responders. Patients with no tumor assessment after the start of study treatment were considered nonresponders. (NCT00127933)
Timeframe: post 2 and 4, 3-week cycles of treatment
| Intervention | percentage of participants (Number) |
|---|
| HER2-Neu Negative | 23.8 |
| HER2-Neu Positive | 23.5 |
Number of Participants With Over-expression of p27 (>75% Cells With Nuclear Staining)
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Sections were rated according to the percentage of tumor cells nuclei with positive staining (1 = < 25%; 2 = between 25-75% and 3 = > 75%). (NCT00129376)
Timeframe: Up to 29 weeks
| Intervention | Participants (Count of Participants) |
|---|
| < 75% | > 75% |
|---|
| Doxorubicin + Cyclophosphamide Followed Docetaxel | 24 | 17 |
Number of Participants With Over-expression of Survivin (>1% Cells With Nuclear Staining)
Paraffin-embedded tumors were processed with standard immunocytochemical techniques. Tumors with more than 1% of cells with nuclear staining were considered to be over-expressing this protein. (NCT00129376)
Timeframe: Up to 29 weeks
| Intervention | Participants (Count of Participants) |
|---|
| > 1 % | < 1% |
|---|
| Doxorubicin + Cyclophosphamide Followed Docetaxel | 18 | 26 |
Pathological Complete Response (pCR) Rate
Pathological complete response was defined by the Miller & Payne criteria. pCR was defined as no invasive cells identifiable in breast sections at surgery. Response was measured by physical exam and breast imaging before surgery and was evaluated according to the World Health Organization (WHO) criteria. Pathological response after surgery, was based on the proportion of remaining tumor and postchemotherapy changes, evaluating separately the response in the breast and in the axilla lymph nodes. (NCT00129376)
Timeframe: Up to 29 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Doxorubicin + Cyclophosphamide Followed Docetaxel | 11 |
Number of Participants With Disease-free Survival (DFS) Event
A participant was considered to have had a DFS event if there was evidence of local, regional or metastatic recurrence, second primary cancer (with the exception of carcinoma of squamous cells or basal cells of the skin, cervical carcinoma in situ or lobular or ductal carcinoma in situ of the breast) or death for any reason. (NCT00129935)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: EC-T | 127 |
| Arm B: ET-X | 170 |
The Number of Participants Who Experienced Adverse Events (AE)
Safety was assessed by standard clinical and laboratory tests, and were evaluated using NCI-CTC criteria v2.0 (NCT00129935)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: EC-T | 665 |
| Arm B: ET-X | 699 |
Quality of Life Questionnaire: Time to Taking Off the Wig
"Time to taking off the wig was assessed by a specific Hair Toxicity Questionnaire were patients answered when they stop to use the wig.~The questionnaire was evaluated up to two years after the end of chemotherapy." (NCT00129935)
Timeframe: Up to 30 months
| Intervention | Months (Median) |
|---|
| Arm A: EC-T | 8.35 |
| Arm B: ET-X | 6.03 |
Number of Participants With Overall Survival (OS) Event
A participant was considered to have had a OS event if patient died from any cause. (NCT00129935)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: EC-T | 70 |
| Arm B: ET-X | 83 |
The Primary Goal of This Study is to Show That the Addition of Bevacizumab to Cisplatin-based Chemotherapy in the Neoadjuvant Setting for Non-squamous Cell Carcinomas Improves Therapeutic Response/Outcome Assessment.
These criteria have been modified for the purpose of this study (i.e.: there will be no confirmation of response at 4 weeks per usual response criteria as this is not applicable to the preoperative treatment plan): Complete Response (CR): Disappearance of all clinical evidence of tumor. Partial Response (PR): A 50% or greater decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Minor Response (MR): A > 25% and < 50% decrease in the sum of the products of measured lesions. No simultaneous increase in the size of any lesion or the appearance of new lesions may occur. Non-measurable lesions must remain stable or regress for this category. Stable Disease (SD): A less than 25% decrease. This includes a decrease of less than 25% in the sum of the products of the meas (NCT00130780)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| A: Pre-surgical Treatment With Bevacizumab Plus Chemotherapy | 51 |
| B: Pre-Surgical Docetaxel, Cisplatin, and Adjuvant Bevacizumab | 20 |
Number of Participants With Progression-Free Survival
The primary objective of this study is to determine whether adding early chemotherapy based on docetaxel plus prednisone compared to standard of care alone reduces disease progression as evidenced by detectable PSA in high risk patients with prostate cancer who have undergone radical prostatectomy. (NCT00132301)
Timeframe: Up to 100 months (centralized follow-up)
| Intervention | Participants (Count of Participants) |
|---|
| Arm 1: Docetaxel and Prednisone | 66 |
| Arm 2: Standard of Care | 84 |
Compare Progression-free Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.
Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients without progression are censored at date of last contact. Disease progression is defined by confirmed bone disease progression, soft tissue or pain progression. (NCT00134056)
Timeframe: Up to 7 years after study opens
| Intervention | months (Median) |
|---|
| Arm I: Placebo | 9.1 |
| Arm II: Atrasentan | 9.2 |
Number of Patients With a Change in Functional Status
Functional status will be measured with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index. The FACT-P also addresses four general domains of QOL (physical, functional, emotional, and social well-being subscales) as well as symptom concerns associated with prostate cancer and its treatment. (NCT00134056)
Timeframe: up to 18 months study period
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Placebo | 118 |
| Arm II: Atrasentan Hydrochloride | 139 |
Compare Survival Between a Control or Standard Therapy Arm of Docetaxel + Placebo + Prednisone With Docetaxel + Atrasentan + Prednisone in Patients With Hormone Refractory Prostate Cancer.
Measured from date of registration to date of death due to any cause. Patient last known to be alive are censored at date of last contact. (NCT00134056)
Timeframe: Up to 7 years after study opens
| Intervention | months (Median) |
|---|
| Arm I: Placebo | 17.6 |
| Arm II: Atrasentan | 17.8 |
Compare Pain Progression Between the Two Study Arms.
Pain progression is defined as patients reporting an increase of at least two Worst Pain points, maintained for at least two consecutive assessments, increase to Level 3 (strong opioid) on the Pain Medication Log Analgesic Code for patients receiving Level 2 (weak opioid) analgesics at randomization, or an increase to Level 2 or 3 analgesics for patients receiving Level 0 or 1 analgesics at randomization. (NCT00134056)
Timeframe: Up to 52 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Placebo | 59 |
| Arm II: Atrasentan | 41 |
Compare Elements of Quality of Life Between Treatment Arms: Pain Palliation Response, as Measured by the Brief Pain Inventory (BPI)
"Pain palliation is the proportion of patients showing a two-point reduction in the Worst Pain score (WPS) maintained for two consecutive assessments with no increase in analgesic use. Increase in analgesic use is defined as an increase in Analgesic code Level to 2 (weak opioid) or 3 (strong opioid). Patients will be classified as pain palliated or not palliated. Patients with a WPS of 0 will be defined as stable if their WPS remains 0 for Weeks 7 and 10 with no increase in analgesic use, but they will not be categorized as responders. Pain palliation response is measured by BPI short form that has the following: yes/no question about pain today; 4 pain rating questions (worst pain, least pain, average pain, and current pain); pain medications and pain relief; 7 items addressing effect of pain on functioning. For patients who continue to receive treatment beyond 12 treatment cycles, the Worst Pain item is measured by Pain Medication Log and Pain Assessment" (NCT00134056)
Timeframe: up to 18 months study period
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Placebo | 75 |
| Arm II: Atrasentan | 83 |
Compare Prostate Specific Antigen (PSA) Response Rates Between the Experimental Arm and the Standard Arm.
PSA Partial Response: Greater than or equal to 50% reduction in baseline PSA. There must be no evidence of soft tissue progression, or confirmed none disease progression, or pain progression. (NCT00134056)
Timeframe: Up to 7 years after study opens
| Intervention | Participants (Count of Participants) |
|---|
| Arm I: Placebo | 243 |
| Arm II: Atrasentan | 249 |
Compare Qualitative and Quantitative Toxicity Between the Two Study Arms
Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT00134056)
Timeframe: Assessed every 3 weeks up to 52 weeks
| Intervention | Participants (Number) |
|---|
| ALT, SGPT (serum glutamic pyruvic transaminase) | AST, SGOT | Adult respiratory distress syndrome (ARDS) | Albumin, serum-low (hypoalbuminemia) | Alkaline phosphatase | Allergic reaction/hypersensitivity | Allergy/Immunology-Other (Specify) | Amylase | Anorexia | Arthritis (non-septic) | Aspiration | Auditory/Ear-Other (Specify) | Bilirubin (hyperbilirubinemia) | Blood/Bone Marrow-Other (Specify) | CNS cerebrovascular ischemia | CPK (creatine phosphokinase) | Calcium, serum-low (hypocalcemia) | Cardiac Arrhythmia-Other (Specify) | Cardiac General-Other (Specify) | Cardiac troponin I (cTnI) | Cardiac troponin T (cTnT) | Cardiac-ischemia/infarction | Conduction abnormality NOS | Confusion | Constipation | Cough | Creatinine | Dehydration | Diarrhea | Dizziness | Dry mouth/salivary gland (xerostomia) | Dysphagia (difficulty swallowing) | Dyspnea (shortness of breath) | Edema: head and neck | Edema: limb | Edema: trunk/genital | Erectile dysfunction | Esophagitis | Fatigue (asthenia, lethargy, malaise) | Febrile neutropenia | Fever in absence of neutropenia, ANC lt1.0x10e9/L | Fracture | Glucose, serum-high (hyperglycemia) | Glucose, serum-low (hypoglycemia) | Heartburn/dyspepsia | Hemoglobin | Hemolysis | Hemorrhage, Respiratory tract NOS | Hemorrhage, GI - Rectum | Hemorrhage, GI - Stomach | Hemorrhage, GI - Upper GI NOS | Hemorrhage, GU - Bladder | Hemorrhage/Bleeding-Other (Specify) | Hemorrhoids | Hot flashes/flushes | Hypertension | Hypotension | Hypoxia | INR (of prothrombin time) | Induration/fibrosis (skin and subcutaneous tissue) | Inf (clin/microbio) w/Gr 3-4 neuts - Bladder | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | Inf (clin/microbio) w/Gr 3-4 neuts - Bronchus | Inf (clin/microbio) w/Gr 3-4 neuts - Esophagus | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | Inf (clin/microbio) w/Gr 3-4 neuts - Nerve-periph | Inf (clin/microbio) w/Gr 3-4 neuts - Skin | Inf (clin/microbio) w/Gr 3-4 neuts - Soft tissue | Inf (clin/microbio) w/Gr 3-4 neuts - UTI | Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | Inf w/normal ANC or Gr 1-2 neutrophils - Bronchus | Inf w/normal ANC or Gr 1-2 neutrophils - Colon | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | Inf w/normal ANC or Gr 1-2 neutrophils - Muscle | Inf w/normal ANC or Gr 1-2 neutrophils - Scrotum | Inf w/normal ANC or Gr 1-2 neutrophils - Sinus | Inf w/normal ANC or Gr 1-2 neutrophils - Skin | Inf w/normal ANC or Gr 1-2 neutrophils - Stomach | Inf w/normal ANC or Gr 1-2 neutrophils - Trachea | Inf w/normal ANC or Gr 1-2 neutrophils - UTI | Inf w/normal ANC or Gr 1-2 neutrophils - Ungual | Inf w/unknown ANC - Middle ear (otitis media) | Inf w/unknown ANC - Upper aerodigestive NOS | Infection with unknown ANC - Blood | Infection with unknown ANC - Lung (pneumonia) | Infection with unknown ANC - Upper airway NOS | Infection with unknown ANC - Urinary tract NOS | Infection-Other (Specify) | Insomnia | Left ventricular diastolic dysfunction | Left ventricular systolic dysfunction | Leukocytes (total WBC) | Lipase | Lymphopenia | Magnesium, serum-high (hypermagnesemia) | Metabolic/Laboratory-Other (Specify) | Mood alteration - agitation | Mood alteration - depression | Mucositis/stomatitis (clinical exam) - Oral cavity | Mucositis/stomatitis (clinical exam) - Pharynx | Mucositis/stomatitis (clinical exam) - Stomach | Mucositis/stomatitis (functional/symp) - Esophagus | Mucositis/stomatitis (functional/symp) - Oral cav | Mucositis/stomatitis (functional/symp) - Pharynx | Mucositis/stomatitis (functional/symp) - Rectum | Muscle weakness, not d/t neuropathy - Extrem-lower | Muscle weakness, not d/t neuropathy - body/general | Myocarditis | Nail changes | Nasal cavity/paranasal sinus reactions | Nausea | Neuropathy: motor | Neuropathy: sensory | Neutrophils/granulocytes (ANC/AGC) | Opportunistic inf associated w/gt=Gr 2 lymphopenia | PTT (Partial thromboplastin time) | Pain - Abdomen NOS | Pain - Back | Pain - Bone | Pain - Chest wall | Pain - Chest/thorax NOS | Pain - Extremity-limb | Pain - Joint | Pain - Muscle | Pain - Neuralgia/peripheral nerve | Pain - Pelvis | Pain-Other (Specify) | Phosphate, serum-low (hypophosphatemia) | Platelets | Pneumonitis/pulmonary infiltrates | Pneumothorax | Potassium, serum-high (hyperkalemia) | Potassium, serum-low (hypokalemia) | Pulmonary/Upper Respiratory-Other (Specify) | Rash: hand-foot skin reaction | Renal failure | Renal/Genitourinary-Other (Specify) | Right ventricular dysfunction (cor pulmonale) | SVT and nodal arrhythmia - Atrial fibrillation | SVT and nodal arrhythmia - Atrial flutter | SVT and nodal arrhythmia - Sinus tachycardia | Sodium, serum-low (hyponatremia) | Somnolence/depressed level of consciousness | Speech impairment (e.g., dysphasia or aphasia) | Sudden death | Syncope (fainting) | Thrombosis/embolism (vascular access-related) | Thrombosis/thrombus/embolism | Vasovagal episode | Vomiting | Watery eye (epiphora, tearing) | Weight gain |
|---|
| Arm I: Placebo | 2 | 2 | 3 | 3 | 4 | 5 | 0 | 0 | 5 | 1 | 0 | 1 | 0 | 2 | 0 | 2 | 7 | 2 | 1 | 2 | 1 | 2 | 1 | 1 | 3 | 1 | 4 | 9 | 10 | 3 | 1 | 1 | 38 | 0 | 16 | 1 | 2 | 0 | 60 | 8 | 1 | 1 | 20 | 1 | 1 | 47 | 1 | 0 | 1 | 1 | 0 | 0 | 2 | 0 | 2 | 2 | 9 | 10 | 3 | 1 | 1 | 2 | 0 | 0 | 11 | 1 | 1 | 1 | 4 | 0 | 2 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 3 | 0 | 1 | 4 | 1 | 1 | 3 | 101 | 0 | 30 | 1 | 0 | 1 | 1 | 2 | 1 | 1 | 0 | 3 | 0 | 0 | 2 | 11 | 1 | 0 | 2 | 11 | 7 | 10 | 140 | 1 | 1 | 4 | 1 | 5 | 0 | 1 | 1 | 2 | 8 | 1 | 0 | 0 | 3 | 7 | 7 | 1 | 2 | 11 | 0 | 1 | 4 | 1 | 0 | 3 | 1 | 0 | 8 | 1 | 0 | 2 | 3 | 0 | 9 | 0 | 8 | 0 | 0 |
,| Arm II: Atrasentan | 2 | 4 | 0 | 0 | 6 | 6 | 1 | 1 | 5 | 0 | 1 | 0 | 1 | 2 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 4 | 2 | 1 | 8 | 7 | 1 | 0 | 1 | 17 | 1 | 2 | 0 | 0 | 1 | 40 | 20 | 2 | 0 | 24 | 0 | 1 | 22 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 2 | 1 | 2 | 3 | 3 | 1 | 0 | 2 | 0 | 1 | 1 | 6 | 0 | 2 | 0 | 3 | 2 | 1 | 1 | 0 | 5 | 0 | 1 | 0 | 2 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 3 | 1 | 0 | 2 | 98 | 1 | 32 | 0 | 2 | 0 | 0 | 2 | 0 | 0 | 1 | 3 | 1 | 1 | 1 | 8 | 0 | 1 | 0 | 5 | 6 | 11 | 154 | 1 | 0 | 0 | 2 | 8 | 1 | 0 | 1 | 2 | 3 | 1 | 1 | 1 | 0 | 4 | 0 | 0 | 1 | 2 | 1 | 0 | 2 | 0 | 1 | 2 | 1 | 1 | 3 | 0 | 1 | 0 | 1 | 1 | 11 | 2 | 7 | 1 | 1 |
Time to PSA Progression
Defined as the time from start of study treatment to first documentation of PSA progression using the PSA Working Group criteria calculated as (first event date - first dose date + 1)/7. PSA progression is defined for patients with a PSA response, as a 50% increase over nadir (lowest) and increase in absolute-value PSA level by at least 5 nanograms per milliliter (ng/mL) [or back to baseline] and for patients without a PSA response as a 25% increase over baseline [or nadir (lowest)] and increase in absolute-value PSA level by at least 5 ng/mL, both confirmed by a second value. (NCT00137436)
Timeframe: Baseline to first documentation of PSA progression up to 28 days after date of last dose
| Intervention | weeks (Median) |
|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | 42.1 |
Percentage of Participants With Prostate Specific Antigen (PSA) Response
PSA response rate, which is defined as a greater than or equal to a 50% decrease in PSA from baseline, that is subsequently confirmed. (NCT00137436)
Timeframe: Baseline, Day 1 of each 21-day cycle
| Intervention | percentage of participants (Median) |
|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | 56.4 |
Percentage of Participants With Objective Response Rate (ORR)
Defined as confirmed complete response (CR: disappearance of all target lesions) or confirmed partial response (PR: ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD) according to response evaluation criteria in solid tumors (RECIST). Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. (NCT00137436)
Timeframe: Baseline to first documentation of PSA progression up to 28 days after date of last dose
| Intervention | percentage of participants (Number) |
|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | 42.4 |
Duration of PSA Response (DPR)
Defined as time from first documentation of PSA response (≥50% decrease in PSA from baseline that is subsequently confirmed) to first documentation of PSA progression (defined for patients with a PSA response as a 50% increase over nadir [lowest] and increase in absolute-value PSA level by at least 5 ng/mL [or back to baseline] and for patients without a PSA response as a 25% increase over baseline [or nadir / lowest] and increase in absolute-value PSA level by at least 5 ng/mL, both confirmed by a second value). Calculated as (end date for DPR - first PSA response + 1)/7. (NCT00137436)
Timeframe: Baseline to first documentation of PSA progression up to 28 days after date of last dose
| Intervention | weeks (Median) |
|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | 39.1 |
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire (FACT-General and Prostate Cancer Subscale)
Assesses health related quality of life and advanced prostate cancer specific symptoms. FACT-General (FACT-G) assesses 4 domains: physical, social and family, emotional, and functional well-being. The prostate cancer subscale assesses prostate cancer symptoms focusing on pain, urination problems, and sexual functions. Individual scores range from 0 (not at all) to 4 (very much). Scores for some of the individual questions are reverse-coded in order for higher scores to correspond to better health status. FACT-P overall score range is 0 to 156; higher scores indicate better health status. (NCT00137436)
Timeframe: Baseline (C1.D1), Day 1 of Cycles 2 through 16, and End of Treatment (EOT=following Cycle 16 or within 7 days of withdrawal from study)
| Intervention | scores on a scale (Mean) |
|---|
| Bsl mean C1.D1 (n=47) | Change from Bsl - C2.D1 (n=42) | Change from Bsl - C3.D1 (n=31) | Change from Bsl - C4.D1 (n=30) | Change from Bsl - C5.D1 (n=33) | Change from Bsl - C6.D1 (n=31) | Change from Bsl - C7.D1 (n=29) | Change from Bsl - C8.D1 (n=25) | Change from Bsl - C9.D1 (n=24) | Change from Bsl - C10.D1 (n=22) | Change from Bsl - C11.D1 (n=21) | Change from Bsl - C12.D1 (n=18) | Change from Bsl - C13.D1 (n=16) | Change from Bsl - C14.D1 (n=17) | Change from Bsl - C15.D1 (n=12) | Change from Bsl - C16.D1 (n=12) | Change from Bsl - EOT (n=36) |
|---|
| SU011248 37.5 mg + Docetaxel 75 mg/m^2 + Prednisone 5 mg | 112.0 | 6.4 | 7.2 | 6.6 | 4.9 | 8.2 | 4.4 | 3.6 | 0.2 | 2.0 | 3.1 | 4.1 | 5.6 | 7.9 | 4.1 | 6.2 | 0.6 |
Response Rate
Response rate by RECIST criteria to the combination of oxaliplatin and docetaxel in patients with previously untreated NSCLC. Per RECIST 1.0 defines a complete response (CR)as the disappearance of all disease. A partial response(PR) as a minimum of a 30% decrease in the sum of the longest dimension of target lesions. Progressive disease (PR) is defined as a minimum of a 20% increase in the sum of the longest dimension of target lesions. Stable disease is defined as neither sufficient shrinkage to qualify as a PR nor sufficient increase to qualify as PD. (NCT00145418)
Timeframe: Response is measured every 2 cycles until disease progression
| Intervention | Participants (Number) |
|---|
| partial response | complete response | stable disease |
|---|
| Oxaliplatin + Docetaxel | 7 | 0 | 1 |
Duration of Response
Duration of response is a measure of how long the participants response to therapy was maintained. (NCT00145418)
Timeframe: 0 -12 months
| Intervention | months (Median) |
|---|
| Oxaliplatin + Docetaxel | 7.9 |
Safety Objective is to Describe the Safety Profile of 1st Line Treatment by Recording Grade 3 and 4 Adverse Events Experienced by Participants in This Trial.
Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE V 3.0) and the incidence of any Grade 3 or 4 toxicities will be analyzed. Toxicity is assessed every cycle. (NCT00145418)
Timeframe: day one of cycle one until participant removed from trial
| Intervention | participants (Number) |
|---|
| Grade 3 or 4 anemia | grade 3 or 4 thrombocytopenia | Grade 3 or 4 fatigue | Grade 3 or 4 dehydration | Grade 3 or 4 nausea | Grade 3 or 4 diarrhea | Grade 3 or 4 anorexia | Grade 3 or 4 neutropenia | Grade 3 or 4 vomiting |
|---|
| Oxaliplatin + Docetaxel | 1 | 1 | 5 | 2 | 1 | 2 | 1 | 3 | 2 |
Time to Progression
Progression is measured from each participants start of study until removal from treatment. (NCT00145418)
Timeframe: <1 cycle to 6 cycles of treatment
| Intervention | months (Median) |
|---|
| Oxaliplatin + Docetaxel | 2.4 |
Probability of Progression Free Survival
The estimated 1 year progression free survival. Progression was defined, using RECIST (Response Evaluation Criteria In Solid Tumors Criteria), as a 20% increase in the sum of the longest diameter of target lesions, the development of any new lesion, or the significant clinical deterioration related to the progression of patient's disease. The probability of progression-free survival was presented in a Kaplan-Meier curve to illustrate the distribution of progression time. The median time to progression was determined with a 95% CI (Confidence Interval). (NCT00148122)
Timeframe: 1 year post treatment
| Intervention | percentage of patients (Number) |
|---|
| Arm 1 | 25 |
Frequency of Grade III/IV Toxicities Experienced by Participants
The frequency of grade 3 and grade 4 adverse events experienced by all treated participants. (NCT00148122)
Timeframe: 30 days post treatment
| Intervention | participants (Number) |
|---|
| Grade 3 and 4 Lymphopenia | Grade 3 and 4 Infection w/o Neutropenia | Grade 3 and 4 Fatigue | Grade 3 and 4 Leukocytes | Grade 3 and 4 Stomatitis | Grade 3 and 4 Neutrophils | Grade 3 and 4 Diarrhea | Grade 3 and 4 Hand-Foot Skin Reaction | Grade 3 and 4 Hemoglobin | Grade 3 and 4 Platelets | Grade 3 and 4 Allergic Reaction | Grade 3 and 4 Anorexia | Grade 3 and 4 Cardiac-Ischemia | Grade 3 and 4 Dysphagia | Grade 3 and 4 Dyspnea | Grade 3 and 4 Abnormal ENT Examination | Grade 3 and 4 Edema Limbs | Grade 3 and 4 Febrile Neutropenia | Grade 3 and 4 Hand-Foot Syndrome | Grade 3 and 4 Hyperglycemia | Grade 3 and 4 Hyponatremia | Grade 3 and 4 Infection with Unknown ANC | Grade 3 and 4 Infection, Lung | Grade 3 and 4 Melena | Grade 3 and 4 Mental Status Changes | Grade 3 and 4 Mucositis | Grade 3 and 4 Nausea | Grade 3 and 4 Oral Pain | Grade 3 and 4 Pain, Extremity | Grade 3 and 4 Pharyngolaryngeal Pain | Grade 3 and 4 AST Elevation | Grade 3 and 4 Vomiting |
|---|
| Arm 1 | 8 | 5 | 4 | 4 | 4 | 3 | 2 | 2 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Overall Response Rate at 4 Months
Disease was assessed by radiologic imaging and RECIST (Response Evaluation Criteria in Solid Tumors) was used to determine response: 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. (NCT00148122)
Timeframe: 4 months
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 16 |
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
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 17 |
| Arm 2 | 31 |
Disease-free Survival
Disease-free survival is defined as the time from date of study enrollment (randomization) to first date of progressive disease (PD) or death from any cause. PD per Response Evaluation Criteria In Solid Tumors (RECIST) criteria is at least a 20% increase in the sum of 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. For patients not known to have died as of the data cut-off date and who do not have progressive disease, disease-free survival was censored at the last contact date. (NCT00149214)
Timeframe: baseline through post surgery, follow-up for 3 years post-surgery (up to 5.2 years after randomization)
| Intervention | months (Median) |
|---|
| Pemetrexed Plus Doxorubicin, Followed by Docetaxel | NA |
| Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel | NA |
Number of Patients With Histologically Negative Axillary Lymph Node Status at Surgery
Histologically negative is defined as no malignant cells present in the axillary lymph nodes during surgery. (NCT00149214)
Timeframe: surgery after eight 21-day cycles of chemotherapy
| Intervention | participants (Number) |
|---|
| Pemetrexed Plus Doxorubicin, Followed by Docetaxel | 64 |
| Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel | 63 |
Number of Participants With a Pathological Complete Response
pathological assessment of tissue removed during surgery to determine if tumor tissue is still present after chemotherapy (NCT00149214)
Timeframe: surgery after eight 21-day cycles of chemotherapy
| Intervention | participants (Number) |
|---|
| Pathological Complete Response | Tumor Cells Still Present | Not evaluable |
|---|
| Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel | 24 | 89 | 6 |
,| Pemetrexed Plus Doxorubicin, Followed by Docetaxel | 21 | 99 | 7 |
Number of Participants With a Clinical Tumor Response After the First Sequence of Chemotherapy
The number of participants with a clinical tumor response based on measurement of tumor size after the first sequence of chemotherapy, without a second confirmatory tumor measurement, per protocol. (NCT00149214)
Timeframe: Cycles 1-4 (21-day cycles)
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Unknown | Not Done |
|---|
| Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel | 9 | 43 | 44 | 2 | 17 | 4 |
,| Pemetrexed Plus Doxorubicin, Followed by Docetaxel | 8 | 45 | 49 | 3 | 17 | 9 |
Number of Participants With a Clinical Tumor Response After the Second Sequence of Chemotherapy
The number of participants with a clinical tumor response based on measurement of tumor size after the second sequence of chemotherapy, without a second confirmatory tumor measurement required, per protocol. (NCT00149214)
Timeframe: Cycles 5-8 (21-day cycles)
| Intervention | participants (Number) |
|---|
| Complete Tumor Response | Partial Tumor Response | Stable Disease | Progressive Disease | Unknown | Not Done |
|---|
| Cyclophosphamide Plus Doxorubicin, Followed by Docetaxel | 21 | 60 | 24 | 1 | 10 | 3 |
,| Pemetrexed Plus Doxorubicin, Followed by Docetaxel | 19 | 59 | 35 | 2 | 9 | 7 |
Overall Survival
The time interval between the date on which a patient first received protocol treatment and the documented date of death. (NCT00177255)
Timeframe: 2 years
| Intervention | Months (Median) |
|---|
| Docetaxel + Capecitabine | 10.7 |
Overall Response Rate
The number of responders (complete responders + partial responders) divided by the number of evaluable patients. (NCT00177255)
Timeframe: Every 2 cycles (6 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel + Capecitabine | 28.2 |
Progression-free Survival (PFS)
Time between the first day of treatment and disease progression. Progression is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Progressive disease is a minimum of 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new measurable lesions. (NCT00179309)
Timeframe: 19.7 months
| Intervention | Months (Median) |
|---|
| Arm I - PANVAC + Docetaxel | 6.6 |
| Arm II - Docetaxel Alone | 3.8 |
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. (NCT00179309)
Timeframe: 80 months
| Intervention | Participants (Number) |
|---|
| Arm I - PANVAC + Docetaxel | 23 |
| Arm II - Docetaxel Alone | 23 |
Tumor Response Type: CR, PR, SD or PD
Tumor response will be based on the RECIST v1.0 criteria. CR (complete response)= disappearance of all target lesions, PR (partial response)= greater or equal to 30% decrease in sum of longest diameter of target lesions, SD (stable disease)= <30% decrease or <20% increase, PD (progressive disease)= greater or equal to 20% increase in longest diameter of target lesions. For patients with an elevated CA-125 as the only evidence of disease, a PR was defined as a decrease of 50% or more lasting at least 8 weeks (Rustin et al. JCO 14:1545-51, 1996). Disease assessment performed every 2 cycles (1 cycle = 21 days). Responders included CR and PR. (NCT00183794)
Timeframe: 6 months after enrollment of last participant
| Intervention | Participants (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Gemcitabine and Docetaxel | 1 | 4 | 9 | 6 |
Progression Free Survival
Progression free survival is measured from the start of treatment until the time the participant is first recorded as having disease progression, or death due to any cause. If a participant has not progressed or died, progression free survival is censored at the time of the last follow up. (NCT00183872)
Timeframe: every 2 cycles
| Intervention | Months (Median) |
|---|
| Arm 1 - Irinotecan and Docetaxel | 4.1 |
Objective Response (Complete, Partial, Stable and Progression)
Objective response was defined using standard RECIST criteria. CR (complete response) = disappearance of all target lesions; PR (partial response) = 30% decrease in the sum of the longest diameter or target lesions; PD (progressive disease) = 20% increase in the sum of the longest diameter of target lesions SD (stable disease) = small changes that do not meet criteria of CR, PR, and PD. (NCT00183872)
Timeframe: every 2 cycles
| Intervention | participants (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Arm 1 - Irinotecan and Docetaxel | 0 | 7 | 22 | 9 |
Tumor Response
"All eligible patients who received the first dose of Taxotere will be included in the analysis.~Tumor Response will be categorized as: Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), Early Death from Malignant Disease.~Per RECIST criteria, CR = disappearance of all target and nontarget lesions; PR = at least a 30% decrease in the sum of the largest 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 PD taking as references the smallest sum LD since the treatment started; PD = at least a 20% increase in the sum of 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." (NCT00184028)
Timeframe: 6 months after the last subject enrolled has gone off study
| Intervention | Participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Early Offstudy (refused further therapy) | Early Death (due to malignant disease) |
|---|
| Arm 1 | 0 | 1 | 5 | 2 | 3 | 1 |
Number of Participants With Serious Adverse Events (SAEs)
Safety evaluation according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. (NCT00184028)
Timeframe: At end of every cycle
| Intervention | Participants (Number) |
|---|
| Taxotere Followed by Oxaliplatin | 7 |
The Percentage of Patients Alive Without Disease at 2 Years
Disease-free survival (NCT00189137)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| Doxorubicin and Ifosfamide | 57 |
| Gemcitabine and Docetaxel | 74 |
Percentage of Patients Hospitalized in Each Arm.
To contrast the proportion of treated patients hospitalized subsequent to treatment with gemcitabine and docetaxel as compared to doxorubicin and ifosfamide as neoadjuvant or adjuvant therapy of poor prognosis soft tissue sarcoma. (NCT00189137)
Timeframe: 12 weeks
| Intervention | percentage of patients hospitalized (Number) |
|---|
| Doxorubicin and Ifosfamide | 35 |
| Gemcitabine and Docetaxel | 26 |
Overall Survival
Overall survival is the duration from enrollment to death from any cause. For patients who are alive, overall survival is censored at the last contact. (NCT00191139)
Timeframe: baseline to date of death from any cause up to 2057 days
| Intervention | days (Median) |
|---|
| Gemcitabine | 492.5 |
| Gemcitabine Plus Docetaxel | 899.0 |
2-Year Survival
Percentage of participants alive at 2 years. (NCT00191139)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Gemcitabine | 40.6 |
| Gemcitabine Plus Docetaxel | 55.7 |
Number of Patients 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. The total number of CRs plus PRs equals overall response rate (ORR). (NCT00191139)
Timeframe: randomization and every 3 months up to 2 years of post-study followup
| Intervention | participants (Number) |
|---|
| Gemcitabine | 24 |
| Gemcitabine Plus Docetaxel | 27 |
Lung Cancer Symptom Scale (LCSS) Assessment Post-randomization
LCSS measures physical & functional dimensions. The patient scale contains 9 items, 3 summation & 6 symptom items. Each item is marked on a visual analog scale (0=low; 100=high). The mean of the 6 symptoms is used to calculate the average symptom burden index (ASBI). Improved=mean ASBI assessments from any 2 consecutive improved post-randomization assessments was at least 0.5 standard deviation (SD) below pre-randomization ASBI; worse=mean ASBI from any 2 consecutive post-randomization assessments was at least 0.5 SD above pre-randomization ASBI; stable=criteria for improved/worse not met. (NCT00191139)
Timeframe: baseline to 3 months after last dose of study treatment (three 21-day cycles)
| Intervention | participants (Number) |
|---|
| Improvement | Stable | Worse |
|---|
| Gemcitabine | 8 | 10 | 2 |
,| Gemcitabine Plus Docetaxel | 5 | 9 | 8 |
Progression-Free Survival
Defined as the time from randomization into consolidation treatment to the first date of documented disease progression or death. Progression-free survival time was censored at the date of the last follow-up visit at which disease was assessed for patients who were still alive and who had not progressed. (NCT00191139)
Timeframe: baseline to measured progressive disease up to 2057 days
| Intervention | days (Median) |
|---|
| Gemcitabine | 162.5 |
| Gemcitabine Plus Docetaxel | 408.0 |
Duration of Response (Crossover Treatment)
At crossover treatment, duration of response was measured from the time criteria were met for complete response (CR) or partial response (PR), until first date that recurrent or progressive disease was objectively documented or date of death due to any cause, whichever came first. This definition only applied to those who crossed over & achieved CR or PR in crossover treatment. Duration of response censored at earliest of: 1) date of last contact for those alive without disease progression; or 2) start date of other anti-tumor therapy for documented disease progression. (NCT00191152)
Timeframe: Date of CR or PR until first date of recurrent or progressive disease after receiving crossover treatment was objectively documented or date of date due to any cause, whichever came first (up to 82 months)
| Intervention | months (Median) |
|---|
| Capecitabine | 25.89 |
| Gemcitabine | 42.50 |
Best Overall Response (Initial Treatment)
Best overall response was the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response was assessed 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 did not meet above criteria. (NCT00191152)
Timeframe: Best response from start of treatment until disease progression/recurrence (up to 82 months)
| Intervention | participants (Number) |
|---|
| Complete Response (confirmed) | Partial Response (confirmed) | Stable Disease | Progressive Disease | Unknown |
|---|
| Docetaxel Plus Capecitabine | 6 | 79 | 90 | 27 | 34 |
,| Gemcitabine Plus Docetaxel | 6 | 71 | 96 | 32 | 34 |
Duration of Response (Initial Treatment)
Among tumor responders, duration of tumor response was 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 response was censored at the earliest of: 1) date of last contact for participants alive without disease progression (DP); or 2) start date of other anti-tumor therapy for DP; or 3) dose date of crossover treatment. (NCT00191152)
Timeframe: Date of response (CR or PR) until the first date of documented progression or death from any cause (up to 82 months)
| Intervention | months (Median) |
|---|
| Gemcitabine Plus Docetaxel | 9.11 |
| Docetaxel Plus Capecitabine | 10.39 |
Progression-Free Survival (Crossover Treatment)
For crossover treatment, progression-free survival (PFS) was defined as the number of months between first dose date of crossover treatment and date of documented disease progression or date of death due to any cause, whichever came first. PFS for crossover treatment only applied to those participants who crossed over from initial treatment to crossover treatment. PFS was censored at the earliest of: 1) date of last contact for participants alive without disease progression; or 2) start date of other anti-tumor therapy for participants with documented disease progression. (NCT00191152)
Timeframe: First dose date of crossover treatment to date of first-documented progression after receiving crossover treatment or date of death due to any cause, whichever came first (up to 82 months)
| Intervention | months (Median) |
|---|
| Capecitabine | 4.51 |
| Gemcitabine | 2.34 |
Overall Survival
Overall survival time was defined as the number of months between the date of randomization and the date of death due to any cause. The overall survival time was censored at the date of last contact for participants who were still alive. (NCT00191152)
Timeframe: Date of randomization to date of death from any cause (up to 82 months)
| Intervention | months (Median) |
|---|
| Gemcitabine Plus Docetaxel | 22.99 |
| Docetaxel Plus Capecitabine | 23.29 |
Progression-Free Survival (Initial Treatment)
For initial treatment, progression-free survival (PFS) was defined as the number of months between the date of randomization and the date of first documented disease progression or the date of death due to any cause, whichever came first. Time to PFS was censored at the earliest of: 1) date of last contact for participants alive without disease progression; or 2) start date of other anti-tumor therapy for progression; or 3) first dose date of crossover treatment. (NCT00191152)
Timeframe: Date of randomization until the date of first documented progression or date of death from any cause, whichever came first (up to 82 months)
| Intervention | months (Median) |
|---|
| Gemcitabine Plus Docetaxel | 9.01 |
| Docetaxel Plus Capecitabine | 8.88 |
Summary of Changes in Rotterdam Symptom Checklist by Treatment (Crossover Treatment)
RSCL includes 4 scales to assess quality of life (QOL) endpoints: 1) a 23-item physical distress level with scale score ranges from 23 to 92 [low score represents better QOL] 2)a 7-item psychological distress level with scale score ranges from 7 to 28[low score represents better QOL] 3)8-item activity level with scale score ranges from 8 to 32 [high score represents better QOL]; 1-item overall valuation of life with score range from 1 to 7 [low score represents better QOL]. (NCT00191152)
Timeframe: First day of crossover treatment until end of crossover treatment at trial discontinuation (up to 82 months)
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline |
|---|
| Capecitabine | 75.00 | -2.78 |
,| Gemcitabine | 76.39 | -0.69 |
Time to Disease Progression (Initial Treatment)
Time to disease progression (TTDP) at initial treatment was defined as the number of months between date of randomization and the date of first documented disease progression or the date of death due to disease under study, whichever came first. TTDP censored at earliest of: 1) date of death not due to disease; or 2) date of last contact for participants alive without disease progression; or 3) start date of other anti-tumor therapy; or 4) first dose date of crossover treatment. (NCT00191152)
Timeframe: Randomization date to the earliest date of first documented disease progression date or the date of death if the participant died due to study disease (up to 82 months)
| Intervention | months (Median) |
|---|
| Gemcitabine Plus Docetaxel | 9.28 |
| Docetaxel Plus Capecitabine | 8.88 |
Time to Disease Progression (Crossover Treatment)
For crossover treatment, time to disease progression (TTDP) was defined as the number of months between the first dose date of crossover treatment and the date of disease progression or the date of death due to disease under study, whichever came first. TTDP for crossover treatment only applied to those participants who crossed over from initial treatment to crossover treatment. TTDP censored at earliest of: 1)date of death not due to disease; or 2)date of last contact for participants alive without disease progression; or 3)start date of other anti-tumor therapy due to progression. (NCT00191152)
Timeframe: Date of first dose of crossover treatment to date of first-documented disease progression after receiving first crossover treatment or date of death due to study disease, whichever came first (up to 82 months)
| Intervention | months (Median) |
|---|
| Capecitabine | 4.51 |
| Gemcitabine | 2.34 |
Summary of Changes in Rotterdam Symptom Checklist (RSCL) by Treatment (Initial Treatment)
RSCL includes 4 scales to assess quality of life (QOL) endpoints: 1) a 23-item physical distress level with scale score ranges from 23 to 92 [low score represents better QOL] 2)a 7-item psychological distress level with scale score ranges from 7 to 28[low score represents better QOL] 3)8-item activity level with scale score ranges from 8 to 32 [high score represents better QOL]; 1-item overall valuation of life with score range from 1 to 7 [low score represents better QOL]. (NCT00191152)
Timeframe: Baseline until crossover treatment began (up to 82 months)
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change from Baseline |
|---|
| Docetaxel Plus Capecitabine | 72.32 | -2.68 |
,| Gemcitabine Plus Docetaxel | 68.09 | 2.42 |
Best Overall Response (Crossover Treatment)
Best overall response was the best response recorded from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response assessed using 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 did not meet above criteria. (NCT00191152)
Timeframe: Best response from start of treatment until disease progression/recurrence (up to 82 months)
| Intervention | participants (Number) |
|---|
| Complete Response (confirmed) | Partial Response (confirmed) | Stable Disease | Progressive Disease | Unknown |
|---|
| Capecitabine | 1 | 10 | 19 | 34 | 13 |
,| Gemcitabine | 1 | 6 | 20 | 36 | 18 |
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.
PFS was defined as the interval from first study treatment until the date that the first progression of breast cancer was documented, or death occurred. (NCT00193037)
Timeframe: 18 Months
| Intervention | months (Median) |
|---|
| Arm A -Liposomal Doxorubicin Then Docetaxel | 6.5 |
| Arm B - Docetaxel Then Liposomal Doxorubicin | 5.5 |
Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment
ORR is defined as the percentage of patients who exhibit a Complete Response (CR) or Partial Response (PR). Complete Response is the total disappearance of clinically and radiologically detectable disease for at least 4 weeks. Partial Response is at least a 50% reduction of all measurable lesions as measured by the product of the perpendicular diameters of the greatest dimensions of tumor size, with no new lesions appearing for at least four weeks. (NCT00193037)
Timeframe: 18 Months
| Intervention | percentage of patients (Number) |
|---|
| Arm A -Liposomal Doxorubicin Then Docetaxel | 28 |
| Arm B - Docetaxel Then Liposomal Doxorubicin | 31 |
Time to Treatment Failure (TTF)
"Time to Treatment Failure (TTF) is defined as the minimum of the time from first date of treatment to the either of the following dates:~disease progression date (RECIST or clinical)~death date~treatment discontinuation" (NCT00193050)
Timeframe: 69 months
| Intervention | months (Median) |
|---|
| Intervention | 13 |
Overall Survival (OS)
Number of participants that are alive at 48th months (NCT00193050)
Timeframe: 48 months
| Intervention | Participants (Count of Participants) |
|---|
| Intervention | 72 |
Pathologic Complete Response (pCR)
For the purpose of this study, a Pathologic complete response (pCR) was defined as no evidence of residual invasive tumor in the breast (pT0). Residual ductal or lobular carcinoma in situ was not considered in pCR assessments. Percentage of participants who experienced pCR is reported. (NCT00193050)
Timeframe: 18 Months
| Intervention | percentage of participants (Number) |
|---|
| Intervention | 18 |
Overall Survival (OS)
Length of time, in months, that patients were alive from their first date of protocol treatment until death. (NCT00193128)
Timeframe: 36 months
| Intervention | months (Median) |
|---|
| Oxaliplatin/Docetaxel/Capecitabine/Radiation (Cohort 2) | 24.1 |
Disease-Free Survival (DFS)
Defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death from any cause. (NCT00193128)
Timeframe: 18 months
| Intervention | months (Median) |
|---|
| Oxaliplatin/Docetaxel/Capecitabine/Radiation (Cohort 2) | 16.3 |
Pathologic Complete Response Rate (PCRR), the Percentage of Patients Who Have No Evidence of Cancer in Their Surgical Specimen Following Surgery
The absence of any residual tumor cells in a histologic evaluation of a tumor specimen following surgery is defined as a complete pathologic response (NCT00193128)
Timeframe: 18 months
| Intervention | Participants (Count of Participants) |
|---|
| Oxaliplatin/Docetaxel/Capecitabine/Radiation (Cohort 2) | 24 |
Overall Response Rate (ORR)
Defined as the proportion of patients with confirmed complete or partial response (CR or PR), recorded from date of treatment until date of recurrence or progressive disease, and assessed by RECIST v 1.1. (NCT00193180)
Timeframe: 18 months
| Intervention | percentage of participants (Number) |
|---|
| Intervention | 16 |
Overall Survival (OS)
Defined as the time from first protocol treatment to date of death due to any cause. (NCT00193180)
Timeframe: 18 months
| Intervention | months (Median) |
|---|
| Intervention | 15.4 |
Progression Free Survival (PFS)
PFS defined as the length of time, in months, that patients were alive from date of first protocol treatment until worsening of disease, assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. (NCT00193180)
Timeframe: 18 months
| Intervention | Months (Median) |
|---|
| Intervention | 9.3 |
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
| Intervention | Months (Median) |
|---|
| Intervention | 18 |
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
| Intervention | percentage of participants (Number) |
|---|
| Intervention | 30 |
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
| Intervention | Percentage of participants (Number) |
|---|
| Intervention | 0 |
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
| Intervention | Months (Median) |
|---|
| Intervention | 9.9 |
Response Duration
The Response Duration was calculated from time of initial measured response to date of first observation of progressive disease. (NCT00193453)
Timeframe: 18 months
| Intervention | Months (Median) |
|---|
| Intervention | 7.0 |
Progression Free Survival (PFS)
Progression free survival was defined as the interval between the start date of treatment and the date of occurrence of progressive disase or death from any cause. (NCT00193453)
Timeframe: 18 months
| Intervention | Months (Median) |
|---|
| Intervention | 4.0 |
Overall Clinical Response Rate
Overall response rate was defined as the proportion of treated patients whose best response was a complete or partial response after completing at least two courses of treatment. (NCT00193453)
Timeframe: 18 months
| Intervention | Percentage of participants (Number) |
|---|
| Intervention | 17 |
Determine Objective 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. (NCT00201825)
Timeframe: Every 35 days
| Intervention | patients (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Stable Disease | Disease Progression | Overall response (CR + PR) |
|---|
| Docetaxel and Capecitabine | 0 | 5 | 14 | 9 | 5 |
Time to Tumor Progression
(NCT00201825)
Timeframe: Every 35 days
| Intervention | months (Median) |
|---|
| Docetaxel and Capecitabine | 3.3 |
One Year Survival
(NCT00201825)
Timeframe: one year
| Intervention | months (Median) |
|---|
| Docetaxel and Capecitabine | 10.5 |
To Measure the Change in Left Ventricular Ejection Fraction (LVEF) From Baseline
Absolute change in LVEF, where LVEF values are measured in percentage units (NCT00203502)
Timeframe: Immediately before treatment and 1 year after start of treatment
| Intervention | Percentage of LVEF (Mean) |
|---|
| Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | -3.5 |
Percentage of Participants With Pathologic Complete Response (pCR) Among Those With Triple Negative Breast Cancer
pCR rate for triple negative patients--percent (NCT00203502)
Timeframe: at surgery, one day
| Intervention | % pCR among triple negative pts (Number) |
|---|
| Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | 57 |
Percentage of Participants With Pathological Complete Response.
Pathological complete response was defined as the absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the resected breast. (NCT00203502)
Timeframe: Participants were assessed during surgery, an average of one hour
| Intervention | percentage of evaluable patients (Number) |
|---|
| Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | 41 |
Number of Participants With Clinical Complete Response in Breast and the Axillary Lymph Nodes After the Completion of Chemotherapy and Bevacizumab.
Clinical complete response was defined using RECIST response categories as the clinical response to chemotherapy (NCT00203502)
Timeframe: At completion of chemotherapy treatment, an average of one hour
| Intervention | percentage of pts w/ cCR (Number) |
|---|
| Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | 53 |
Percentage of Participants With Grade 3 or 4 Adverse Events
Percent of participants who had at least one grade 3 or 4 adverse event (NCT00203502)
Timeframe: After each chemotherapy infusion, approximately one hour
| Intervention | percentage of pts w/ grade 3/4 AE (Number) |
|---|
| Intervention: Drug:Docetaxel + Cyclophosphamide + Avastin | 79 |
Overall Survival
(NCT00206518)
Timeframe: 10 years
| Intervention | participants (Number) |
|---|
| deceased | alive |
|---|
| A: Taxotere/Docetaxel | 16 | 67 |
,| B: AC Adriamycin/Cytoxan | 19 | 65 |
Pathological Tumor Response to Neoadjuvant Chemotherapy (Taxotere and AC)
"The patients' pathological response were assessed using Chevalier's system which graded the responses into Chevalier 1, 2, 3A, 3B, 3C, 3D, and 4, defined as:~Disappearance of all tumor either on macroscopic or microscopic assessment in both the breast and LN (pCR)~Presence of in situ carcinoma in the breast. No invasive tumor in breast and no tumor in LN (pCR)~Presence of invasive cancer with stromal alteration such as sclerosis or fibrosis (pPR) 3A: Subjectively > 75% therapeutic effect 3B: Subjectively between 50% - 75% therapeutic effect 3C: Subjectively between 25% - 50% therapeutic effect 3D: Subjectively < 25% therapeutic effect OR Grade 4~No or few modification of tumoral appearance (pNR)." (NCT00206518)
Timeframe: 10 years
| Intervention | participants (Number) |
|---|
| 1 | 2 | 3A | 3B | 3C | 3D | 4 | N/A |
|---|
| A: Taxotere/Docetaxel | 3 | 2 | 18 | 15 | 18 | 10 | 3 | 14 |
,| B: AC Adriamycin/Cytoxan | 9 | 1 | 15 | 18 | 15 | 8 | 0 | 18 |
Disease Relapse
Data associated with relapse and progression will be obtained over the course of 10 years. Relapse/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. (NCT00206518)
Timeframe: 10 years
| Intervention | participants (Number) |
|---|
| relapsed | not relapsed |
|---|
| A: Taxotere/Docetaxel | 24 | 59 |
,| B: AC Adriamycin/Cytoxan | 25 | 59 |
Long Term Follow up Data on Recurrence and Survival
Number of Patients remained alive and relapse free (NCT00209092)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Arm A:Sequential Therapy | 19 |
| Arm B:Concurrent Therapy | 21 |
Number of Participants With Complete Pathologic Response Rate to Pre-operative Treatment in Arm A (Docetaxel for 4 Cycles Followed by Capecitabine for 4 Cycles) or Arm B (Docetaxel + Capecitabine for 8 Cycles) in Patients With Early Stage Breast Cancer.
"Pathologic complete response (pCR): Absence of invasive breast cancer in the breast.~Overall Clinical Response=Complete response(CR-complete disappearance of all measurable malignant disease)+partial response(PR-reduction by at least 30%)~Stable disease (SD): No decrease or <25% increase in the sum of the products of the longest perpendicular diameters of all measurable lesions.~Progressive disease (PD): A 20% or greater increase in a single lesion, OR reappearance of any lesion which has disappeared, OR clear worsening of any evaluable disease OR appearance of any new lesion/site." (NCT00209092)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| Pathologic Complete Response-Overall population | Overall Clinical Response | Stable disease | Progressive Disease |
|---|
| Arm A:Sequential Therapy | 2 | 15 | 3 | 7 |
,| Arm B:Concurrent Therapy | 3 | 23 | 1 | 2 |
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
| Intervention | Participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Not Assessible |
|---|
| Double Agent Chemotherapy | 0 | 23 | 23 | 6 | 1 |
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
| Intervention | Months (Median) |
|---|
| Double Agent Chemotherapy | 6.6 |
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
| Intervention | Months (Median) |
|---|
| Double Agent Chemotherapy | 13.3 |
Overall Survival
A comparison of overall survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median survival time and a log rank test were used to analyze the hypothesized improvement in overall survival. (NCT00216125)
Timeframe: Participants were measured from treatment initiation to death
| Intervention | Months (Median) |
|---|
| Consolidation Docetaxel | 21.5 |
| Observation Only | 24.1 |
Progression Free Survival
"A comparison of progression free survival following cisplatin/etoposide/radiotherapy between the consolidation docetaxel and observation arms was analyzed using Kaplan-Meier analysis. Median PFS time and a log rank test were used to analyze the hypothesized improvement in progression free survival.~Progression is defined by RECIST as a 20% increase in the sum of longest diameters of target measurable lesions over the smallest sum observed (over baseline if no decrease during therapy) or by the appearance of a new lesion." (NCT00216125)
Timeframe: Participants were monitored from treatment initiation until disease progression per RECIST or death
| Intervention | months (Median) |
|---|
| Consolidation Docetaxel | 12.3 |
| Observation Only | 12.9 |
Overall Survival
Overall survival using the Kaplan-Meier method (NCT00217581)
Timeframe: Patients will be followed for survival every three months after they are off study or until their disease progresses, for up to two years
| Intervention | months (Median) |
|---|
| Docetaxel, Oxaliplatin & Bevacizumab | 11.1 |
Response Rate by RECIST Criteria
Percentage of Participants with response by RECIST criteria until progression (NCT00217581)
Timeframe: After every 2 cycles (1 cycle =21 days)
| Intervention | percentage of responders (Number) |
|---|
| Docetaxel, Oxaliplatin & Bevacizumab | 42 |
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 (NCT00217581)
Timeframe: After every 2 cycles (1 cycle =21 days) From study registration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 18 months
| Intervention | months (Median) |
|---|
| Docetaxel, Oxaliplatin & Bevacizumab | 6.6 |
Time to Treatment Failure
Time to treatment failure using the Kaplan-Meier method (NCT00217581)
Timeframe: Every 21 days From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
| Intervention | months (Median) |
|---|
| Docetaxel, Oxaliplatin & Bevacizumab | 4.5 |
Toxicity Profile
Toxicity profile of grade 3 and grade 4 events using the NCI-CTCAE Version 3.0 scale for toxicity grading. (NCT00217581)
Timeframe: At 21 days following completion of study treatment
| Intervention | Participants (Count of Participants) |
|---|
| Neutropenia | Leukopenia | GI Perforation | TE Fistula | Hypertension | Venous Thromboemblism | Neuropathy | Nausea | Vomiting | Diarrhea | Dehydration | Fever | Fatigue | Anorexia |
|---|
| Docetaxel, Oxaliplatin & Bevacizumab | 13 | 1 | 3 | 1 | 2 | 1 | 5 | 4 | 2 | 3 | 4 | 2 | 2 | 2 |
Comparison of Response Rates, Duration of Response, and Overall Survival
(NCT00217672)
Timeframe: Time of death, up to 3 years
| Intervention | months (Median) |
|---|
| Overall Duration of Response (DR) | Overall Observed Response (OR) | ER+ and/or PgR+ DR | ER+ and/or PgR+ OR | ER-/PgR- DR | ER-/PgR- OR | Adjuvantb Chemotherapy Including Taxane DR | Adjuvantb Chemotherapy Including Taxane OR | Adjuvantb Chemotherapy Without Taxane DR | Adjuvantb Chemotherapy Without Taxane OR | No Previous Adjuvant Chemo DR | No Previous Adjuvant Chemo OR |
|---|
| Docetaxel + Bevacizumab | 11.8 | 26.3 | 14.6 | NA | 6.2 | 18.6 | 18.2 | 26.1 | 13.2 | NA | 9.0 | 26.3 |
Comparison of Safety and Toxicity
Evaluated using adverse event (AE) information. Detailed AE information is provided in the AE section. (NCT00217672)
Timeframe: When adverse events occur, up to 30 days after last dose for each subject, up to 3 years from start of study
| Intervention | subjects (Number) |
|---|
| dose reduction of docetaxel for toxicity | dose delay or interruption | discontinued docetaxel and continued to receive be | bevacizumab dose delay or interruption | patients came off of study because of bevacizumab- |
|---|
| Docetaxel + Bevacizumab | 10 | 19 | 10 | 24 | 9 |
Antitumor Activity Based on Time to Tumor Progression (TTP).
(NCT00217672)
Timeframe: From randomization until tumor progression
| Intervention | months (Median) |
|---|
| Docetaxel + Bevacizumab | 9.3 |
Biochemical Progression-free Survival (PFS)
Measure of the activity of a treatment on a disease. In this study it is measured from the date of enrollment to the date on which the prostate cancer progresses or the date the patient dies. Survival curves were estimated using the Kaplan-Meier technique. Biochemical (PSA) failure is defined, in accordance to the American Society for Therapeutic Radiology and Oncology consensus definition, as three consecutive rise in PSA. The date of biochemical failure is considered to be the midpoint between the last non-rising PSA and the first rising PSA. (NCT00225420)
Timeframe: Average follow up of 2 years
| Intervention | percentage of patients (Mean) |
|---|
| Single Arm | 94 |
Number of Patients Experiencing Dose-Limiting Toxicities
Determine the number of patients experiencing dose-limiting toxicities (DLT) at each dose level. DLT was defined as grade 3-4 non-haematological or grade 4 haematological toxicity, using the Common Terminology Criteria for Adverse Events, version 3.0. (NCT00225420)
Timeframe: Average follow up of 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel at 10 mg/m2 | 1 |
| Docetaxel 15 mg/m2 | 1 |
| Docetaxel 20 mg/m2 | 0 |
2-year Overall Survival (OS)
Two-year OS is an estimated percentage of participants still living at two years after the start of study treatment. (NCT00226239)
Timeframe: Up to 24 months
| Intervention | percentage of participants (Number) |
|---|
| Head and Neck Cancer Patients | 84 |
3-year Overall Survival (OS)
Three-year OS is an estimated percentage of participants still living at three years after the start of study treatment. (NCT00226239)
Timeframe: Up to 36 months
| Intervention | percentage of participants (Number) |
|---|
| Head and Neck Cancer Patients | 74 |
Objective Response Rate (ORR)
Objective response rate is defined as the percentage of participants with a best response of complete response or partial response. Disease assessments were based on Response Evaluation Criteria in Solid Tumors (RECIST), version 1.0. (NCT00226239)
Timeframe: Up to 36 months
| Intervention | percentage of participants (Number) |
|---|
| Head and Neck Cancer Patients | 86 |
,| Head and Neck Cancer Patients | 100 |
Progression-free Survival (PFS)
PFS is an estimated percentage of participants without disease progression at two years (or three years) after the start of study treatment. Progression was defined using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0. The two-year and three-year PFS ended up being the same in this study. (NCT00226239)
Timeframe: Up to 36 months
| Intervention | percentage of participants (Number) |
|---|
| two-year PFS | three-year PFS |
|---|
| Head and Neck Cancer Patients | 70 | 70 |
Quality of Life (QOL)
"Effect of treatment on acute and late QOL and functional status using Functional Assessment of Cancer Therapy-General (FACT-G) with FACT-Head and Neck (FACT-HN) subscale. The instructions to the participant were: Below is a list of statements that other people with your illness have said are important. By circling one number per line, please indicate how true each statement has been for you during the past 7 days. The choices for each statement ranged from 0 (not at all) to 4 (very much). The FACT-G and FACT-Head and Neck total scores were computed by summing 27 and 39 questions respectively, for four subscales: physical well-being, social well-being, emotional well-being, and functional well-being. Questions for both assessments are phrased so that higher numbers/values indicate a better health state." (NCT00226239)
Timeframe: Pre-treatment, Post-induction, 3 months after XPE and 12 months after XPE
| Intervention | units on a scale (Mean) |
|---|
| FACT-G Total Score Pre-treatment | FACT-G Total Score Post-induction | FACT-G Total Score 3 months after XPE | FACT-G Total Score 12 months after XPE | FACT-HN Pre-treatment | FACT-HN Post-induction | FACT-HN 3 months after XPE | FACT-HN 12 months after XPE |
|---|
| Head and Neck Cancer Patients | 77.4311 | 75.6303 | 71.3864 | 86.6702 | 25.7000 | 25.1250 | 19.4545 | 24.5263 |
Progression-free Survival
Progression-free survival estimated using Kaplan-Meier's product-limit method. (NCT00227721)
Timeframe: Every two cycles until disease progression or death, assessed up to 5 years
| Intervention | months (Median) |
|---|
| Docetaxel & Gemcitabine Hydrochloride | 7.2 |
Response Rate to the Combination of Gemcitabine and Docetaxel in Patients With Platinum Sensitive and Resistant Epithelial Ovarian or Peritoneal Cancer.
(NCT00227721)
Timeframe: Disease status by Response Evaluation Criteria In Solid Tumors Criteria (RECIST) or Gynecological Cancer Intergroup (GCIG) CA-125 criteria was assessed every two cycles from enrollment up to progression, death, or five years (whichever occurred first).
| Intervention | percentage of participants with CR or PR (Number) |
|---|
| Docetaxel & Gemcitabine Hydrochloride | 62 |
Overall Response Rate (ORR)
ORR: Complete Response (CR) + Partial Response (PR). Response rate for Elderly (> 70 years) previously untreated patients with Stage IIIb (With Malignant Pleural Effusion (MPE)) or IV non-small cell lung cancer (NSCLC) receiving Taxotere + ZD1839. Best clinical response to treatment with combination was determined using Response Evaluation Criteria in Solid Tumors (RECIST V1.0): * 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, taking as reference the baseline sum LD; * 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; * 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. (NCT00231465)
Timeframe: Duration of time on study, an average of 19 months
| Intervention | percentage of participants (Mean) |
|---|
| Taxotere® (Docetaxel) + ZD1839 (IRESSA®) | 40 |
Overall Survival (OS) Rate
OS was calculated from the date of enrollment to the date of death. All 44 treated were assessed for OS, with a minimum follow-up of 19 months. (NCT00231465)
Timeframe: Duration of time on study, an average of 19 months
| Intervention | Months (Median) |
|---|
| Taxotere® (Docetaxel) + ZD1839 (IRESSA®) | 9.59 |
Progression Free Survival (PFS) Rate
PFS was calculated from the date of enrollment to the date of progression. All 44 treated were assessed for PFS, with a minimum follow-up of 19 months. Progression (PD): At least a 20% increase in the sum of 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. (NCT00231465)
Timeframe: Duration of time on study, an average of 19 months
| Intervention | Months (Median) |
|---|
| Taxotere® (Docetaxel) + ZD1839 (IRESSA®) | 6.9 |
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.
| Intervention | participants (Number) |
|---|
| Group 1 | 1 |
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
| Intervention | participants (Number) |
|---|
| Group 1 | 19 |
Overall Survival (OS) by Treatment Drug
OS is the duration from enrollment to time of death as a result of any cause. For participants who are alive, OS is censored at the last contact (date of the last follow-up visit). (NCT00236899)
Timeframe: Baseline up to 51.64 months
| Intervention | months (Median) |
|---|
| Treatment Drug (Docetaxel) | 19.11 |
| Treatment Drug (Paclitaxel) | 23.80 |
Overall Survival (OS) by Treatment Schedule
OS is the duration from enrollment to time of death as a result of any cause. For participants who are alive, OS is censored at the last contact (date of the last follow-up visit). (NCT00236899)
Timeframe: Baseline up to 51.64 months
| Intervention | months (Mean) |
|---|
| Treatment Schedule (Weekly) | 21.11 |
| Treatment Schedule (3 Weekly) | 20.95 |
Time to Progressive Disease (TTPD) by Treatment Drug
"TTPD is defined as the time from the day of treatment to first observation of documented disease progression or death due to any cause, whichever comes first. TTPD was censored at the time of last follow-up for patients who were still alive without progression. Tumor response was assessed in cancer patients by using Response Evaluation Criteria in Solid Tumors (RECIST), which define when cancer patients improve (respond), stay the same (stabilize), or worsen (progression) during treatments. Progressive Disease is a ≥20% increase in sum of longest diameter of target lesions." (NCT00236899)
Timeframe: Baseline up to 49.84 months
| Intervention | months (Median) |
|---|
| Treatment Drug (Docetaxel) | 7.74 |
| Treatment Drug (Paclitaxel) | 7.80 |
Number of Participants With Serious and Nonserious Adverse Events (AEs)
Summary tables of serious adverse events (SAEs) and all other nonserious AEs are located in the Reported Adverse Event Module. (NCT00236899)
Timeframe: Baseline up to 51.64 months
| Intervention | participants (Number) |
|---|
| SAEs | Nonserious AEs |
|---|
| Arm A: Docetaxel and Gemcitabine (Tri-weekly) | 9 | 57 |
,| Arm B: Paclitaxel and Gemcitabine (Tri-weekly) | 10 | 58 |
,| Arm C: Docetaxel and Gemcitabine (Weekly) | 7 | 53 |
,| Arm D: Paclitaxel and Gemcitabine (Weekly) | 11 | 56 |
Time to Progressive Disease (TTPD) by Treatment Schedule
"TTPD is defined as the time from the day of treatment to first observation of documented disease progression or death due to any cause, whichever comes first. TTPD was censored at the time of last follow-up for patients who were still alive without progression. Tumor response was assessed in cancer patients by using Response Evaluation Criteria in Solid Tumors (RECIST), which define when cancer patients improve (respond), stay the same (stabilize), or worsen (progression) during treatments. Progressive Disease is a ≥20% increase in sum of longest diameter of target lesions." (NCT00236899)
Timeframe: Baseline up to 49.84 months
| Intervention | months (Median) |
|---|
| Treatment Schedule (Weekly) | 8.33 |
| Treatment Schedule (3 Weekly) | 7.51 |
Quality of Life (QOL) Using the Rotterdam Symptom Scale Checklist (RSSC) at Beginning of 3-Week or 4-Week Cycle
RSSC is a valid and reliable measure of psychological and physical distress of cancer patients. Overall QOL is assessed on a 7-point scale (1=Excellent to 7=Extremely Poor). Categories include Excellent, Good, Moderately Good, Neither Good nor Bad, Rather Poor, Poor, and Extremely Poor. Number of responses to the overall QOL by treatment arm are provided. Arms A (Docetaxel and Gemcitabine 3 Weekly) and B (Paclitaxel and Gemcitabine 3 Weekly) were assessed every 3 weeks. Arms C (Docetaxel and Gemcitabine Weekly) and D (Paclitaxel and Gemcitabine Weekly) were assessed every 4 weeks. (NCT00236899)
Timeframe: Baseline up to 51.64 months
| Intervention | participants (Number) |
|---|
| 1=Excellent | 2=Good | 3=Moderately Good | 4=Neither Good Nor Bad | 5=Rather Poor | 6=Poor | 7=Extremely Poor | No Response |
|---|
| Arm A: Docetaxel and Gemcitabine (Tri-weekly) | 3 | 13 | 6 | 6 | 2 | 0 | 0 | 30 |
,| Arm B: Paclitaxel and Gemcitabine (Tri-weekly) | 1 | 13 | 8 | 7 | 3 | 3 | 3 | 26 |
,| Arm C: Docetaxel and Gemcitabine (Weekly) | 2 | 9 | 9 | 6 | 3 | 7 | 0 | 22 |
,| Arm D: Paclitaxel and Gemcitabine (Weekly) | 4 | 5 | 9 | 7 | 6 | 2 | 1 | 25 |
Quality of Life (QOL) Using the Rotterdam Symptom Scale Checklist (RSSC) at 30-Day Post-therapy Visit
RSSC is a valid and reliable measure of psychological and physical distress of cancer patients. Overall QOL is assessed on a 7-point scale (1=Excellent to 7=Extremely Poor). Categories include Excellent, Good, Moderately Good, Neither Good nor Bad, Rather Poor, Poor, and Extremely Poor. Number of responses to the overall QOL (using the 7-point scale) by treatment arm are provided. (NCT00236899)
Timeframe: Baseline up to 51.64 months
| Intervention | participants (Number) |
|---|
| 1=Excellent | 2=Good | 3=Moderately Good | 4=Neither Good Nor Bad | 5=Rather Poor | 6=Poor | 7=Extremely Poor | No Response |
|---|
| Arm A: Docetaxel and Gemcitabine (Tri-weekly) | 0 | 7 | 2 | 3 | 0 | 2 | 1 | 45 |
,| Arm B: Paclitaxel and Gemcitabine (Tri-weekly) | 0 | 7 | 6 | 6 | 1 | 0 | 0 | 44 |
,| Arm C: Docetaxel and Gemcitabine (Weekly) | 0 | 2 | 3 | 0 | 1 | 1 | 2 | 49 |
,| Arm D: Paclitaxel and Gemcitabine (Weekly) | 0 | 4 | 2 | 3 | 1 | 2 | 0 | 47 |
Overall Response Rate(ORR) by Treatment Drug
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. Not Available=participants assessed whose data were not available. Not Assessed=participants who did not participate in assessments. The ORR=sum of complete and partial tumor responses observed, divided by the total number of evaluable participants. (NCT00236899)
Timeframe: Baseline up to 49.84 months
| Intervention | percentage of responses (Number) |
|---|
| ORR (Complete Response or Partial Response) | Complete Response | Partial Response | Stable Disease | Progressive Disease | Not Available | Not Assessed |
|---|
| Treatment Drug (Docetaxel) | 43.2 | 5.08 | 38.14 | 32.20 | 17.80 | 0.85 | 5.93 |
,| Treatment Drug (Paclitaxel) | 39.8 | 7.32 | 32.52 | 32.52 | 16.26 | 1.63 | 9.76 |
Overall Response Rate (ORR) by Treatment Schedule
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. Not Available=participants assessed whose data were not available. Not Assessed=participants who did not participate in assessments. The ORR=sum of complete and partial tumor responses observed, divided by the total number of evaluable participants. (NCT00236899)
Timeframe: Baseline up to 49.84 months
| Intervention | percentage of responses (Number) |
|---|
| ORR (Complete Response or Partial Response) | Complete Response | Partial Response | Stable Disease | Progressive Disease | Not Available | Not Assessed |
|---|
| Treatment Schedule (3 Weekly) | 33.06 | 5.65 | 27.42 | 40.32 | 12.90 | 1.61 | 12.10 |
,| Treatment Schedule (Weekly) | 50.43 | 6.84 | 43.59 | 23.93 | 21.37 | 0.85 | 3.42 |
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
| Intervention | participants (Number) |
|---|
| Docetaxel+Carboplatin +Radiation+Surgery | 7 |
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
| Intervention | standardized uptake value (SUV)max (Mean) |
|---|
| Docetaxel / Carboplatin / XRT + Surgical Resection | 5.7 |
Survival
Overall Survival using the Kaplan-Meier method (NCT00248560)
Timeframe: Every 8 weeks
| Intervention | months (Median) |
|---|
| Gemcitabine, Docetaxel | 4.2 |
Response (Complete Response [CR] + Partial Response [PR])
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. (NCT00248560)
Timeframe: every 8 weeks for approximately 8 - 48 weeks
| Intervention | participants (Number) |
|---|
| Gemcitabine, Docetaxel | 6 |
Response Duration
Response duration in months (NCT00248560)
Timeframe: Every 8 weeks
| Intervention | months (Median) |
|---|
| Gemcitabine, Docetaxel | 3.2 |
Toxicity as Measured by Number and Grade of Adverse Events
Toxicity as the total number of participants with a given grade 3 and/or grade 4 adverse event (NCT00248560)
Timeframe: Every 2 weeks
| Intervention | participants (Number) |
|---|
| Anemia | Neutropenia | Hyponatremia | Dehydration | Fatigue | Dyspnea | Pneumonia | Thrombocytopenia | Febrile neutropenia | Tachycardia | Syncope | Fluid retention | Mucositis | Hyperglycemia | Constipation | Anorexia | Vomiting | Other non-hematologic toxicity |
|---|
| Gemcitabine, Docetaxel | 13 | 10 | 10 | 3 | 3 | 3 | 3 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Overall Survival (OS)
OS is the amount of time in months from the date of registration to the date of death from any cause. (NCT00251225)
Timeframe: Up to 60 months
| Intervention | months (Median) |
|---|
| Hormone Refractory Prostate Cancer Patients | 23.1 |
Overall Time To Progression (TTP)
TTP is the amount of time from date of registration to date of first documentation of progression or symptomatic deterioration. For progression, one or more of the following must occur: (1) 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. (2) Increase in PSA by at least 25% from baseline in patients whose PSA did not decrease, and of 50% from nadir in patients whose PSA decreased with a confirmation 3 weeks later. (3) Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). (4) Appearance of any new lesion/site. (5) Death due to disease without prior documentation of progression and without symptomatic deterioration, which is defined as global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. (NCT00251225)
Timeframe: Up to 24 months
| Intervention | months (Median) |
|---|
| Hormone Refractory Prostate Cancer Patients | 6.4 |
Prostate-Specific Antigen (PSA) Response Rate
PSA response rate is the number of participants who experienced a best response of: complete response, CR (PSA less than or equal to 0.2 ng/mL, documented two or more times, a minimum of four weeks apart), partial response, PR (a decline in PSA by at least 50%, confirmed by a second PSA value four or more weeks later) or stable disease (does not qualify for CR, PR, Progression or Symptomatic Deterioration, at least 6 weeks after registration) / total number of analyzable patients. (NCT00251225)
Timeframe: Up to 12 months
| Intervention | percentage of patients (Number) |
|---|
| Hormone Refractory Prostate Cancer Patients | 72.4 |
The Proportion of Patients With Objective Response (Complete Response or Partial Response)
Response was evaluated using RECIST (Response Evaluation Criteria in Solid Tumors) 1.0 criteria. Per RECIST criteria, complete response (CR) = disappearance of all target and non-target 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. (NCT00253370)
Timeframe: Assessed every 6 weeks until disease progression or up to 3 years
| Intervention | Proportion of patients (Number) |
|---|
| BAY 43-9006, Docetaxel, Cisplatin | 0.409 |
Progression-free Survival (PFS)
"Progression-free survival was defined as the shorter of:~The time from registration to progression. or~The time from registration to death without documentation of progression given that the death occurs within 4 months of the last disease assessment without progression (or registration, whichever is more recent).~Therefore, cases not meeting either of the criteria for a PFS event are censored at the date of last disease assessment without progression (or registration, whichever is more recent).~Progression is defined as at least 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 non-target lesions." (NCT00253370)
Timeframe: Assessed every 6 weeks until disease progression or up to 3 years
| Intervention | Months (Median) |
|---|
| BAY 43-9006, Docetaxel, Cisplatin | 5.8 |
Overall Survival (OS)
Overall survival was defined as the time from registration to death from any cause. (NCT00253370)
Timeframe: Assessed every 3 months if patient is < 2 years from study entry; then every 6 months if patient is 2-3 years from study entry.
| Intervention | Months (Median) |
|---|
| BAY 43-9006, Docetaxel, Cisplatin | 13.6 |
Progression-free Survival (PFS) in Patients With AJCC Stage IV Metastatic Melanoma Treated With Docetaxel and Vinorelbine as First-line or Post-first Line (Salvage) Systemic Therapy
The primary endpoint is to evaluate the six-month progression-free survival (PFS) in patients with AJCC stage IV metastatic melanoma treated with docetaxel and vinorelbine as first-line or post-first line (salvage) systemic therapy. Progressive disease is defined as any new lesion or a greater than or equal to 20% increase in the largest perpendicular diameter of the sum of the T-lesions identified on contrast enhanced CT or MRI scan. (NCT00256282)
Timeframe: Six months from initial treatment
| Intervention | days (Median) |
|---|
| Docetaxel and Vinorelbine Plus Sargramostim | 134 |
Percentage of Patients Alive at One Year
(NCT00256282)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel and Vinorelbine Plus Sargramostim | 25 |
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
| Intervention | Percentage of Patients (Number) |
|---|
| 1 Year | 2 Years | 3 Years |
|---|
| Patients With Endometrial Cancer | 94 | 91 | 80 |
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
| Intervention | Percentage of Patients (Number) |
|---|
| 1 Year | 2 Years | 3 Years |
|---|
| Patients With Endometrial Cancer | 86 | 76 | 68 |
Left Ventricular Ejection Fraction (LVEF)
LVEF was assessed by echocardiogram (ECHO) or multigated angiogram (MUGA) during neoadjuvant treatment and during follow-up. (NCT00270894)
Timeframe: At screening, prior to cycle 5, prior to surgery, and then during follow-up at Month 6, 12, 24, and 36
| Intervention | LVEF percent (Mean) |
|---|
| Screening | After Epirubicin/Cyclophosphamide | Pre-Surgery | Follow-up Month 6 | Follow-up Month 12 | Follow-up Month 24 | Follow-up Month 36 |
|---|
| Neoadjuvant Therapy | 63.55 | 61.94 | 56.88 | 57.68 | 58.15 | 59.38 | 55.00 |
Frequency of Grade 3 or 4 Hematologic and Nonhematologic Toxicities
Toxicities are evaluated according to the Common Terminology Criteria for Adverse Events, version 3.0. Grade refers to the severity of the adverse event (AE). Generally, 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. (NCT00270894)
Timeframe: Toxicities are evaluated every 2 weeks during neoadjuvant treatment and assessed once during the post-treatment follow-up period, up to 25 weeks.
| Intervention | Events (Number) |
|---|
| CTCAE grade 3 hematologic events | CTCAE grade 3 non-hematologic events | CTCAE grade 4 hematologic events | CTCAE grade 4 non-hematologic events |
|---|
| Neoadjuvant Therapy | 2 | 11 | 0 | 0 |
Clinical Response Prior to Surgery
Clinical response was assessed via physical exam every 2 weeks during neoadjuvant treatment and via imaging prior to definitive surgery. Clinical complete response was defined as no evidence of cancer in breast by exam or imaging. Clinical partial response was defined as >= 50 % reduction in sum of diameters to measurement of primary lesion compared to pretreatment by exam or imaging. Clinical stable disease was defined as < 50% reduction in sum of diameters to measurement of primary lesion compared to pretreatment by exam or imaging, and < 25% increase in sum of diameters. (NCT00270894)
Timeframe: Assessed every 2 weeks during neoadjuvant treatment and prior to definitive surgery, up to 23 weeks.
| Intervention | Participants (Number) |
|---|
| Clinical complete response | Clinical partial response | Clinical stable disease |
|---|
| Neoadjuvant Therapy | 20 | 5 | 2 |
Progression-free Survival (PFS)
PFS is defined as the duration of time from start of treatment to time of progression or death, whichever comes first. (NCT00270894)
Timeframe: PFS was measured from day 1 of treatment until time of progression or death, whichever comes first, assessed up to 48 months.
| Intervention | Months (Median) |
|---|
| Neoadjuvant Therapy | NA |
Percentage of Subjects Able to Complete > 85% of the Planned Dose on Schedule
Feasibility will be determined by evaluating the percentage of subjects able to complete the neoadjuvant portion of the study on time with > 85% of the protocol-specified dose. (NCT00270894)
Timeframe: From the start of treatment through the neoadjuvant treatment period (approximately 20 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Neoadjuvant Therapy | 60 |
Overall Survival (OS)
Overall survival is defined as the time from treatment start until death from any cause. The median overall survival time is used to measure OS. (NCT00270894)
Timeframe: Measured from day 1 of treatment until time of death, assessed up to 48 months.
| Intervention | Months (Median) |
|---|
| Neoadjuvant Therapy | NA |
Pathologic Response
Pathologic response was assessed at time of definitive surgery, scheduled to occur 20-24 weeks after study treatment start. Pathologic complete response was defined as no invasive carcinoma in surgical specimen of breast, but residual ductal carcinoma in situ may be present. Pathologic partial response was defined as >= 50% decrease in sum of diameters in pathologic cancer size compared to pretreatment clinical size. Stable disease was defined as < 50% decrease in sum of diameters in pathologic cancer size compared to pretreatment clinical size, and < 25% increase in sum of diameters. (NCT00270894)
Timeframe: At completion of neoadjuvant treatment period, up to 24 weeks.
| Intervention | Participants (Number) |
|---|
| Pathologic complete response (pCR) | Pathologic partial response (pPR) | Stable disease (SD) |
|---|
| Neoadjuvant Therapy | 16 | 9 | 3 |
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
| Intervention | percentage of participants (Mean) |
|---|
| Carboplatin,Docetaxel, and Bevacizumab | 95 |
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
| Intervention | months (Median) |
|---|
| Carboplatin,Docetaxel, and Bevacizumab | 16.5 |
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
| Intervention | months (Median) |
|---|
| Carboplatin, Docetaxel, and Bevacizumab | 7.9 |
Nadir of Myelosuppression (Over All Cycles) as Measured by Hemoglobin (Hb) Counts
Maximal degree of myelosuppression is represented by the nadir in hemoglobin (Hb) measurements over all treatment cycles. (NCT00274456)
Timeframe: Day 1 up to 125 weeks
| Intervention | g/L (Mean) |
|---|
| ABI-007 300 mg/m^2 q3w | 112.1 |
| ABI-007 100 mg/m^2 Weekly | 106.7 |
| ABI-007 150 mg/m^2 Weekly | 105.6 |
| Docetaxel 100 mg/m^2 q3w | 107.1 |
Percentage of Participants With Stable Disease for ≥ 16 Weeks, or Complete or Partial Overall Response
Known as the disease control rate, this outcome measures the percentage of participants with stable disease for 16 weeks or more, or had a confirmed complete or partial response (see outcome #1 for confirmed response definitions). Assessments made by independent radiology and by investigators are reported separately (NCT00274456)
Timeframe: Day 1 up to 95 weeks
| Intervention | percentage of participants (Number) |
|---|
| Independent Assessed SD Disease Control | Investigator Assessed Disease Control |
|---|
| ABI-007 100 mg/m^2 Weekly | 75 | 83 |
,| ABI-007 150 mg/m^2 Weekly | 80 | 91 |
,| ABI-007 300 mg/m^2 q3w | 68 | 72 |
,| Docetaxel 100 mg/m^2 q3w | 58 | 69 |
Percentage of Participants Showing an Overall Response As Assessed by the Independent Radiology Reader and by the Investigator
Percentage of participants who achieve 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. A partial response (PR) is >= 30% decrease in the sum of the longest diameters of target lesion. PR was also recorded when all measurable disease has completely disappeared, but a non-measurable component (ie, ascites) is still present but not progressing. Overall response (ORR) = CR+PR. (NCT00274456)
Timeframe: Day 1 up to 95 weeks
| Intervention | percentage of participants (Number) |
|---|
| Independent reader assessed ORR | Investigator assessed ORR |
|---|
| ABI-007 100 mg/m^2 Weekly | 45 | 63 |
,| ABI-007 150 mg/m^2 Weekly | 49 | 74 |
,| ABI-007 300 mg/m^2 q3w | 37 | 46 |
,| Docetaxel 100 mg/m^2 q3w | 35 | 39 |
Kaplan-Meier Estimates for Progression-free Survival (PFS)
PFS was defined as the time from the date of randomization to the start of disease progression (PD) or patient death (any cause), whichever occurred first. Patients without disease progression were censored at the last time the patient was known to be progression-free. Patients who initiated new anticancer therapy prior to documented progression or death were censored at the start of new therapy. Disease progression was assessed separately by investigators and by an independent radiologist. Both assessments are offered. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000). PD for target lesions is defined as 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. (NCT00274456)
Timeframe: Day 1 up to 95 weeks
| Intervention | months (Median) |
|---|
| Independent Assessment for PFS | Investigator Assessment for PFS |
|---|
| ABI-007 100 mg/m^2 Weekly | 12.8 | 7.5 |
,| ABI-007 150 mg/m^2 Weekly | 12.9 | 14.6 |
,| ABI-007 300 mg/m^2 q3w | 11.0 | 10.9 |
,| Docetaxel 100 mg/m^2 q3w | 7.5 | 7.8 |
Nadir of Myelosuppression (Over All Cycles) as Measured by Absolute Neutrophils (ANC), White Blood Cells (WBC) and Platelet Counts
Maximal degree of myelosuppression is represented by the nadir in absolute neutrophil (ANC), white blood cell (WBC), and platelet measurements over all treatment cycles. (NCT00274456)
Timeframe: Day 1 up to 125 weeks
| Intervention | 10^9/L (Mean) |
|---|
| ANC | WBC | Platelet |
|---|
| ABI-007 100 mg/m^2 Weekly | 1.51 | 3.15 | 192.1 |
,| ABI-007 150 mg/m^2 Weekly | 1.11 | 2.68 | 172.6 |
,| ABI-007 300 mg/m^2 q3w | 1.21 | 2.88 | 182.1 |
,| Docetaxel 100 mg/m^2 q3w | 0.38 | 1.60 | 161.8 |
Kaplan-Meier Estimate for Overall Survival (OS)
Participant survival was defined as the date of randomization to the date of death. Participants that were alive at the time of analysis were censored at the last known time that the participant was alive. The final analysis of mature overall survival was conducted after 2 years of follow-up (data cutoff date 31 Jan 2010). (NCT00274456)
Timeframe: Day 1 to 221 weeks
| Intervention | months (Median) |
|---|
| ABI-007 300 mg/m^2 q3w | 27.7 |
| ABI-007 100 mg/m^2 Weekly | 22.2 |
| ABI-007 150 mg/m^2 Weekly | 33.8 |
| Docetaxel 100 mg/m^2 q3w | 26.6 |
Kaplan-Meier Estimates for Duration of Response Based on Independent Radiology Assessment of Response and Progression
Duration of response was measured as the progression-free survival on patients with confirmed response. The independent radiology assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. (NCT00274456)
Timeframe: Day 1 - 95 weeks
| Intervention | months (Median) |
|---|
| ABI-007 300 mg/m^2 q3w | 13.0 |
| ABI-007 100 mg/m^2 Weekly | 13.2 |
| ABI-007 150 mg/m^2 Weekly | 15.1 |
| Docetaxel 100 mg/m^2 q3w | 9.0 |
Kaplan-Meier Estimates for Duration of Response Based on Investigator Assessment of Response and Progression
Duration of response was measured as the progression-free survival on patients with confirmed response. The investigator assessment is offered here. Response was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 (Therasse, 2000) and is defined in outcome #1. Progression-free survival is defined in outcome #3. (NCT00274456)
Timeframe: Day 1 - 95 weeks
| Intervention | months (Median) |
|---|
| ABI-007 300 mg/m^2 q3w | 12.9 |
| ABI-007 100 mg/m^2 Weekly | 9.2 |
| ABI-007 150 mg/m^2 Weekly | 14.8 |
| Docetaxel 100 mg/m^2 q3w | 15.1 |
Objective PSA Response Rate (Number of Patients With a PSA Response)
Decline from a baseline value by ≥ 50% or normalization of PSA (< 0.03) confirmed by a second measurement at least 1 week or more weeks later. Patients must not demonstrate clinical or radiographic evidence of disease progression during this time period. The date of response will be defined as the first date at which the PSA declined from baseline by ≥ 50% or normalized. (NCT00276549)
Timeframe: every 4 weeks
| Intervention | participants (Number) |
|---|
| Number of patients with a response ≥ 50% | Number of patients with no response |
|---|
| Gemcitabine (Gemzar) and Docetaxel (Taxotere) | 17 | 18 |
Number of Patients With Measurable Soft Tissue Disease Will be Assessed Per Solid Tumor Response Criteria (RECIST).
Patients who have a response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) by RECIST criteria. To be assigned a status of PR or CR, changes in tumor measurements must be confirmed by repeat assessments that should be performed no less than 4 weeks after the criteria for response are first met. In the case of SD, patients who do not meet the criteria for response or progressive disease for at least 90 days will be categorized as stable disease. (NCT00276549)
Timeframe: at 4 weeks after treatment completion
| Intervention | participants (Number) |
|---|
| Partial Response | Stable Disease |
|---|
| Gemcitabine (Gemzar) and Docetaxel (Taxotere) | 3 | 19 |
6-month Overall Survival
Percentage of patients survived at 6 months for patients whose tumors were xenografted and treated in the mouse when treated with the most active agent identified in that model (NCT00276744)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 53 |
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
| Intervention | percentage of participants (Number) |
|---|
| Neutropenia | Thrombocytopenia | Febrile Neutorpenia | Nausea | Vomiting | Diarrhea | Infusional reactions | Dehydration | Fatigue/asthenia | Syncope | Arrythmia | Proteinuria | Infection | Dyspnea |
|---|
| Grade 3 % | 24 | 1 | 3 | 1 | 1 | 3 | 4 | 1 | 5.5 | 5.5 | 0 | 0 | 0 | 0 |
,| Grade 3/4 % | 65 | 1 | 11 | 1 | 1 | 3 | 4 | 1 | 5.5 | 5.5 | 1 | 1 | 3 | 1 |
,| Grade 4 % | 42 | 0 | 8 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 3 | 1 |
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
| Intervention | percentage of participants (Number) |
|---|
| Single Arm Trial | 86 |
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
| Intervention | percentage of participants (Number) |
|---|
| Single Arm Trial | 86 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Single Arm Trial | 57 |
Response Rate
The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence. The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Response and progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST). A response will be determined by at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD (NCT00281840)
Timeframe: 5 years
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Progressive Disease | Stable Disease |
|---|
| Bevacizumab With Docetaxel and Radiation Therapy | 16 | 6 | 1 | 3 |
Time to Progression
The time to disease progression is calculated from the date of treatment. Data for patients who remain disease progression free are censored as of date when the last follow-up information is obtained. (NCT00281840)
Timeframe: 5 yrs after treatment
| Intervention | Months (Mean) |
|---|
| Bevacizumab With Docetaxel and Radiation Therapy | 44.2 |
Correlation Between Uterine Serosal Involvement and Tumor Response to Treatment (PFS)
AJCC Stage I: No serosal involvement AJCC Stage II: No serosal involement AJCC Stage III: Serosal only (NCT00282087)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| AJCC Stage I | AJCC Stage II | AJCC Stage III |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 0 | 6 | 41 |
Correlation Between Age and Tumor Response to Treatment (PFS)
(NCT00282087)
Timeframe: 2 years
| Intervention | years (Median) |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 53 |
Correlation Between Mitotic Rate and Tumor Response to Treatment (PFS)
Mitotic rate is measured in mitoses per 10 high-power fields (NCT00282087)
Timeframe: 2 years
| Intervention | mitoses per 10 high-power fields (Median) |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 18 |
Tolerability/Toxicity of This Regimen
Unacceptable toxicity is defined as grade 3 or 4 non-hematologic toxicity events that are considered to be treatment-related, excluding alopecia and fatigue. (NCT00282087)
Timeframe: Every 28 days during dosing and then every 3 months thereafter until patient comes off study
| Intervention | number of major toxicity events (Number) |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 6 |
Two-year Progression-free Survival Among Women Treated With This Adjuvant Regimen for High Risk Uterine LMS
(NCT00282087)
Timeframe: Every 3 months up to two years
| Intervention | percentage of participants (Number) |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 78 |
Correlation Between 1988 FIGO Stage and Tumor Response to Treatment (PFS)
Stage I: confined to the uterine corpus Stage II: confined to corpus and cervix Stage IIIA: serosa involvement only (disease could involve the uterine serosa, but patients must have had no other evidence of local spread) (NCT00282087)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| FIFO Stage I | FIGO Stage II | FIGO Stage III |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 38 | 7 | 2 |
Correlation Between Estrogen Receptor (ER) or Progesterone Receptor (PR) Positive and Tumor Response to Treatment (PFS)
(NCT00282087)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| ER or PR Positive | ER and PR Negative |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 33 | 14 |
Correlation Between Estrogen Receptor (ER) Status and Tumor Response to Treatment (PFS)
(NCT00282087)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Positive Status | Negative Status |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 24 | 14 |
Correlation Between Menopausal Status at Diagnosis and Tumor Response to Treatment (PFS)
(NCT00282087)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Postmenopausal | Premenopausal |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 43 | 4 |
Correlation Between Progesterone Receptor (PR) Status and Tumor Response to Treatment (PFS)
(NCT00282087)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Positive Status | Negative Status |
|---|
| Women Treated With Adjuvant Regimen for High Risk Uterine LMS | 19 | 19 |
To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire
"The FACT-P is a 39-item participant questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better QoL with fewer symptoms. A score of 156 represents the best outcome.~Note: Enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn due to the low sample size." (NCT00283062)
Timeframe: from 30 days before randomization (baseline) and 18 months after treatment initiation (for change from baseline)
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Change from Baseline (N=33, N=41, N=12, N=10) |
|---|
| Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | 114.7 | 6.7 |
,| Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | 124.0 | 0.7 |
,| Leuprolide Acetate - Deferred Treatment (D-HT) | 119.7 | 6.1 |
,| Leuprolide Acetate - Immediate Treatment (I-HT) | 121.5 | 1.7 |
Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE)
Number of participants with treatment-emergent adverse events (TEAE). A TEAE was as any adverse event that occurred or worsened during the on-treatment period, which was the period from the day of first infusion of study treatment until 30 days after the last infusion of study treatment. (NCT00283062)
Timeframe: from treatment initiation up to 19 months after treatment initiation
| Intervention | participants (Number) |
|---|
| with any adverse event (AE) | with any serious adverse event (SAE) | with an SAE resulting in death | with a drug-related AE | with a drug-related SAE | with AE leading to discontinue all study therapy | with AE leading to chemotherapy discontinuation | with AE leading to chemotherapy dose reduction |
|---|
| Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | 19 | 5 | 0 | 18 | 2 | 1 | 1 | 2 |
,| Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | 47 | 12 | 0 | 47 | 6 | 2 | 1 | 5 |
,| Leuprolide Acetate - Deferred Treatment (D-HT) | 14 | 2 | 0 | 10 | 0 | 0 | NA | NA |
,| Leuprolide Acetate - Immediate Treatment (I-HT) | 48 | 8 | 0 | 43 | 0 | 0 | NA | NA |
Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression
"PFS is the interval from the date of surgery to date of progression. The date of progression was the earlier of~first PSA increase to ≥ 0.4 ng/mL confirmed within two weeks~date of the nadir, if PSA nadir did not reach < 0.4 ng/mL (for deferred arm)~first radiological/ histological evidence of tumor progression~death. Median PFS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Median PFS could not be estimated. Reported is the number of participants with disease progression." (NCT00283062)
Timeframe: from the date of surgery up to 3 years after randomization of the last participant
| Intervention | participants (Number) |
|---|
| Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) | 10 |
| Leuprolide Acetate - Immediate Treatment (I-HT) | 14 |
| Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) | 9 |
| Leuprolide Acetate - Deferred Treatment (D-HT) | 8 |
Progression-free Survival.
Duration from the date of enrollment until the date of progression (as defined by RECIST: >= 20% increase over baseline in the sum of longest diameters, or appearance of new lesions, or non-measurable disease that is clearly worsening in the opinion of the treating investigator, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and free of disease progression are censored at the date of last contact. (NCT00288054)
Timeframe: At week 10, week 22, and then every 3 months until progression for up to 3 years after enrollment.
| Intervention | months (Number) |
|---|
| Cohort 1: Cetuximab + Radiotherapy (no Docetaxel) | 8 |
Toxicity
Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT00288054)
Timeframe: Weekly for the first 8 weeks, then every 4 weeks while subject on protocol treatment.
| Intervention | Participants (Number) |
|---|
| Allergic reaction/hypersensitivity | Ataxia (incoordination) | Burn | Cardiac troponin I (cTnI) | Cough | Dehydration | Diarrhea | Dyspnea (shortness of breath) | Esophagitis | Fatigue (asthenia, lethargy, malaise) | Hypoxia | Inf (clin/microbio) w/Gr 3-4 neuts - Lung | Left ventricular diastolic dysfunction | Lymphopenia | Magnesium, serum-low (hypomagnesemia) | Muscle weakness, not d/t neuropathy - Extrem-lower | Neurology-Other (Specify) | Neutrophils/granulocytes (ANC/AGC) | Pain - Head/headache | Pain - Skin | Potassium, serum-low (hypokalemia) | Rash: acne/acneiform | Syncope (fainting) | Thrombosis/thrombus/embolism |
|---|
| Cetuximab + Chest Radiation Therapy | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 3 | 1 | 1 | 1 | 1 | 1 | 4 | 3 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 1 |
Overall Survival
The duration form the date of enrollment until the date of death due to any cause. Patients last known to be alive are censored at the date of last contact. (NCT00288054)
Timeframe: weekly while patient is on protocol treatment, then monthly thereafter.
| Intervention | months (Median) |
|---|
| Cohort 1: Cetuximab + Radiotherapy (no Docetaxel) | 14 |
Response Rate
Confirmed and unconfirmed complete and partial responses in the subset of patients with measurable disease (as defined per RECIST). A confirmed complete response (CR) is defined as disappearance of all disease, confirmed by a second determination of CR at least 4 weeks later. A confirmed partial response (PR) is defined as a >= 30% decrease from baseline in the sum of longest diameters, confirmed by a second determination of PR at least 4 weeks later. A patient is considered to have measurable disease if they have at least one lesion with a longest diameter of >= 2 cm by conventional CT, or >= 1 cm by spiral CT. (NCT00288054)
Timeframe: Week 10 and week 22
| Intervention | percentage of participants (Number) |
|---|
| Cohort 1: Cetuximab + Radiotherapy (no Docetaxel) | 47 |
Biochemical Control
Four-year rates are shown (Kaplan-Meier estimates). Biochemical control is defined as freedom from biochemical failure. Biochemical failure was considered as the first of either prostate-specific antigen (PSA) failure or initiation of salvage hormone therapy. PSA failure was defined as a rise of 2 ng/ml over the nadir PSA. Patients who experienced death without biochemical failure, local failure prior to biochemical failure, or development of distant metastases prior to biochemical failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. (NCT00288080)
Timeframe: From randomization to date of biochemical failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + Radiation Therapy | 82.0 |
| Androgen Suppression + Radiation Therapy + Chemotherapy | 84.1 |
Disease-free Survival
A failure for disease-free survival is the first of the following: biochemical failure, local failure, distant metastases, or death due to any cause. The corresponding outcome time was measured from the date of randomization. Disease-free survival rates at 4 years were calculated using the Kaplan-Meier method. (NCT00288080)
Timeframe: From randomization to date of progression, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + Radiation Therapy | 73.0 |
| Androgen Suppression + Radiation Therapy + Chemotherapy | 78.5 |
Local Control
Local control is defined as the absence of local failure which is the first of either progression or recurrence within the prostate. Progression of the tumor was considered to have occurred when there was a 25% or greater increase in the product of the two largest perpendicular diameters of the prostate. Recurrence was defined as the reappearance of disease after a complete response. Patients who experienced death without local failure, biochemical failure prior to local failure, and development of distant metastases prior to local failure were censored on the date of the competing event. The corresponding outcome time was measured from the date of randomization. Due to an insufficient number of events (2 in each arm), this endpoint was not statistically compared. Local control rates at 4 years were calculated using the Kaplan-Meier method. (NCT00288080)
Timeframe: From randomization to date of local failure, death, or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + Radiation Therapy | 99.2 |
| Androgen Suppression + Radiation Therapy + Chemotherapy | 99.5 |
Overall Survival
Four-year rates are shown. 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. (NCT00288080)
Timeframe: From randomization to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 4 years.
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + Radiation Therapy | 88.7 |
| Androgen Suppression + Radiation Therapy + Chemotherapy | 93.3 |
Incidence of Adverse Events
Adverse events are graded using CTCAE v3.0. The worst grade of all adverse events for each patient is counted. (NCT00288080)
Timeframe: From start of treatment until the end of follow-up
| Intervention | percentage of participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Androgen Suppression + Radiation Therapy | 14.9 | 48.4 | 26.0 | 4.3 | 1.4 |
,| Androgen Suppression + Radiation Therapy + Chemotherapy | 2.1 | 25.9 | 40.1 | 28.4 | 0.7 |
Rate of Participants Achieving Complete Response or Partial Response to Therapy.
Rate of participants achieving complete response (CR) or partial response (PR) to Captere therapy according to RECIST criteria v 1.0. 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. (NCT00290693)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Partial Response (PR) >= 2 cycles | Stable Disease (SD), >= 2 cycles | Complete Response (CR), >= 2 cycles |
|---|
| CapTere (Capecitabine + Docetaxel) | 6 | 25 | 0 |
Number of Study Participants Experiencing Toxicity After Receiving Protocol Therapy
Number of study participants experiencing toxicity (serious adverse events or adverse events). Study participants assessed for this outcome measure must have received at least one dose of protocol therapy. Toxicity assessed according to Common Terminology Criteria for Adverse Events v3.0 (CTCAE). (NCT00290693)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| CapTere (Capecitabine + Docetaxel) | 38 |
Overall Surival (OS)
Overall survival is measured from the time from date of initial protocol therapy to date of death. In the absence of confirmation of death, survival time will be censored to last date of follow-up. (NCT00290693)
Timeframe: Up to 1 year
| Intervention | months (Median) |
|---|
| CapTere (Capecitabine + Docetaxel) | 5.3 |
Progression-free Survival (PFS)
Progression-free survival (PFS) is measured the time from the start of protocol therapy to disease progression 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 non-target lesion, or the appearance of new lesions. (NCT00290693)
Timeframe: Up to 1 year
| Intervention | months (Median) |
|---|
| CapTere (Capecitabine + Docetaxel) | 3.7 |
Rate of Participants Achieving a 50% or More Reduction in CA 19-9 Levels
Rate of participants achieving a 50% or more reduction in CA 19-9 levels after receiving protocol therapy. Baseline CA-19-9 will be compared to the lowest recorded value on patients receiving therapy on protocol. A 50% drop in CA 19-9 in patients with baseline levels above 100 U/ml will be recorded as a CA 19-9 response if the > 50% drop can be confirmed with at least one more CA 19-9 level thereafter with > 50% drop compared to baseline. (NCT00290693)
Timeframe: Up to 1 year
| Intervention | percentage of participants (Number) |
|---|
| CapTere (Capecitabine + Docetaxel) | 35.48 |
Duration of Tumor Response Based on Investigator Assessment
Median duration (50%) of tumor response based on Investigator assessment for a subgroup of subjects with objective disease response: who have not progressed or died due to any cause; with a response and subsequent progression or death due to any cause for duration of response (DR). DR defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurs first. DR calculated as (Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7. (NCT00291577)
Timeframe: Start of first confirmed CR or PR to first confirmed progression or death
| Intervention | weeks (Median) |
|---|
| Sunitinib in Combination With Docetaxel | 28.7 |
Number of Subjects With Clinical Benefit of Complete Response, Partial Response, or Stable Disease Based on Investigator Assessment
Number of subjects with clinical benefit based on Investigator assessment of confirmed complete response (CR), partial response (PR), or stable disease (SD) according to RECIST for at least 24 weeks on study. (NCT00291577)
Timeframe: First dose of study treatment until at least 24 weeks on study
| Intervention | participants (Number) |
|---|
| Sunitinib in Combination With Docetaxel | 17 |
Area Under the Curve From Time 0 to Last Quantifiable Concentration (AUClast): Docetaxel PK Parameters
Mean AUClast = area under the plasma concentration-time profile from time 0 (predose) to the last measurable concentration; collected C1D1, C2D1. Paired observation. (NCT00291577)
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
| Intervention | ng*hr/mL (Mean) |
|---|
| C1D1 | C2D1 |
|---|
| Sunitinib in Combination With Docetaxel | 3159.58 | 3304.48 |
Progression-Free Survival (PFS) Based on Investigator Assessment
Median time (50 percent [%]) from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first; based on Investigator assessment. PFS calculated as (Weeks) = (first event date minus first dose date plus 1) divided by 7. (NCT00291577)
Timeframe: First dose of study treatment until progressive disease
| Intervention | weeks (Median) |
|---|
| Sunitinib in Combination With Docetaxel | 34.9 |
Area Under the Curve From Time 24 Hours to 48 Hours (AUC24_48) : Docetaxel PK Parameters
Mean AUC24_48 = area under the plasma concentration-time profile from 24 to 48 hours; collected C1D1, C2D1. Paired observation. (NCT00291577)
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
| Intervention | ng*hr/mL (Mean) |
|---|
| C1D1 | C2D1 |
|---|
| Sunitinib in Combination With Docetaxel | 249.45 | 225.29 |
Area Under the Plasma Concentration-time Curve From Time Zero (0) to 24 Hours (AUC24): Docetaxel PK Parameters
Mean AUC24 = area under the plasma concentration-time profile from time 0 to 24 hours; collected C1D1, C2D1. Paired observation. (NCT00291577)
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
| Intervention | ng*hr/mL (Mean) |
|---|
| C1D1 | C2D1 |
|---|
| Sunitinib in Combination With Docetaxel | 2918.09 | 3101.69 |
Area Under the Plasma Concentration-time Curve From Time Zero (0) to 48 Hours (AUC48): Docetaxel PK Parameters
Mean AUC48 = area under the plasma concentration-time profile from time 0 to 48 hours; collected C1D1, C2D1. Paired observation. (NCT00291577)
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
| Intervention | ng*hr.mL (Mean) |
|---|
| C1D1 | C2D1 |
|---|
| Sunitinib in Combination With Docetaxel | 3167.53 | 3326.98 |
Maximum Observed Plasma Concentration (Cmax): Docetaxel PK Parameters
Mean Cmax = maximum plasma concentration for Docetaxel; collected C1D1, C2D1. Paired observation; Cmax dose corrected (dose correction if predose concentrations of SU011248 or SU012662 were > 5% of Cmax). (NCT00291577)
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
| Intervention | ng/mL (Mean) |
|---|
| C1D1 | C2D1 |
|---|
| Sunitinib in Combination With Docetaxel | 2932.00 | 2955.38 |
Plasma Elimination Half-life (t1/2): Docetaxel PK Parameters
Mean Thalf (t1/2) = terminal elimination half life; collected C1D1, C2D1. Paired observation. (NCT00291577)
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
| Intervention | hours (Mean) |
|---|
| C1D1 | C2D1 |
|---|
| Sunitinib in Combination With Docetaxel | 22.55 | 24.88 |
Time to Reach Maximum Plasma Concentration (Tmax): Docetaxel PK Parameters
Median Tmax = time to maximum plasma concentration (Cmax) for Docetaxel; collected C1D1, C2D1. Paired observation. (NCT00291577)
Timeframe: 0.5, 1, 1.5, 2, 3, 4, 6, 8, 24, 32, 48 hours postdose
| Intervention | hours (Median) |
|---|
| C1D1 | C2D1 |
|---|
| Sunitinib in Combination With Docetaxel | 0.70 | 0.77 |
Number of Subjects With Objective Response of Complete Response or Partial Response Based on Investigator Assessment
Number of subjects with objective response based on Investigator assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. (NCT00291577)
Timeframe: First dose of study treatment until at least 4 weeks after confirmed response or partial response
| Intervention | participants (Number) |
|---|
| Sunitinib in Combination With Docetaxel | 14 |
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.
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide | 11 |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin | 10 |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab | 28 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide | 6 |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin | 4 |
| Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and Trastuzumab | 22 |
CA-125 Response Rate
"A CA-125 response was considered at least a 50% reduction in the level of the biomarker, CA-125, from a pretreatment level, which was confirmed and maintained for at least 28 days.~The overall CA-125 biomarker response rate was defined as the number of participants in the measurable disease subgroup who met the above criteria at least once within the study treatment period +21 days, divided by the number of evaluable participants in the disease subgroup." (NCT00296816)
Timeframe: up to 12 months after treatment initiation
| Intervention | percentage of participants (Number) |
|---|
| With non-measurable disease at baseline (N=27) | With measurable disease at baseline (N=53) |
|---|
| Oxaliplatin/Docetaxel/Bevacizumab | 81.5 | 83.0 |
Overall Survival Rate
"Survival was the observed length of life from entry into the study to death or the date of last contact.~The overall survival rate (percentage of participants showing survival) at 12 and 24-months is reported here." (NCT00296816)
Timeframe: up to up to approximately 1700 days after treatment initiation
| Intervention | percentage of participants (Number) |
|---|
| Overall survival at 12 months | Overall survival at 24 months |
|---|
| Oxaliplatin/Docetaxel/Bevacizumab | 85.5 | 71.8 |
Tumor Response Rate Based on Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST)
"Tumors were assessed by CT and MRI. Tumor response was evaluated by GOG RECIST in which:~Complete response (CR) was the disappearance of all target and non-target lesions, with no evidence of new lesions~Partial response (PR) was at least a 30% decrease in the sum of longest dimensions (LD) of all measurable target lesions~Participants with a response (CR or PR) were to have the initial response confirmed by tumor imaging in 4-6 weeks." (NCT00296816)
Timeframe: up to 12 months following treatment initiation
| Intervention | participants (Number) |
|---|
| Unconfirmed response (CR+PR) | Unconfirmed complete response (CR) | Unconfirmed partial response (PR) | Unconfirmed progressive disease (PD) | Confirmed response (CR+PR) | Confirmed complete response (CR) | Confirmed partial response (PR) |
|---|
| Oxaliplatin/Docetaxel/Bevacizumab | 51 | 23 | 28 | 5 | 41 | 21 | 20 |
Twelve-month Recurrence-free Survival (RFS) Rate in Participants With Non Measurable Disease at Baseline
"Participants with Recurrence-free survival (RFS) were participants with a non-measurable disease at baseline, who had not achieved disease progression nor had died.~Disease progression included the following:~the appearance of a new lesion~symptomatic deterioration~progression of non-target lesions~a predefined serum CA 125 increase.~RFS rate was the percent of participants in the non-measurable disease subgroup who achieved RFS." (NCT00296816)
Timeframe: up to 12 months following treatment initiation
| Intervention | percentage of participants (Number) |
|---|
| Oxaliplatin/Docetaxel/Bevacizumab | 67.5 |
Twenty Four-month Progression-free Survival (PFS) Rate in Participants
"Tumor assessments were performed by Computed tomography (CT) and Magnetic Resonance Imaging (MRI) to evaluate disease progression based on Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST).~Disease progression was recorded as any one of the following:~appearance of a new lesion~symptomatic deterioration~progression of target or nontarget lesions~death~Participants who did not die or show show disease progression achieved PFS. PFS rate is the percent of participants who achieved PFS." (NCT00296816)
Timeframe: up to 24 months following treatment initiation
| Intervention | percentage of participants (Number) |
|---|
| Oxaliplatin/Docetaxel/Bevacizumab | 34.3 |
Twelve-month Progression-free Survival (PFS) Rate in Participants
"Tumor assessments were performed by Computed tomography (CT) and Magnetic Resonance Imaging (MRI) to evaluate disease progression based on Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST).~Disease progression was recorded as any one of the following:~appearance of a new lesion~symptomatic deterioration~progression of target or nontarget lesions~death~Participants who did not die or show show disease progression achieved PFS. PFS rate is the percent of participants who achieved PFS." (NCT00296816)
Timeframe: up to 12 months following treatment initiation
| Intervention | percentage of participants (Number) |
|---|
| Oxaliplatin/Docetaxel/Bevacizumab | 65.7 |
Overall Survival
Overall survival using Kaplan-Meier estimates (NCT00301808)
Timeframe: Date of registration to the date of death
| Intervention | months (Median) |
|---|
| Cisplatin, Docetaxel & Radiation Therapy | 33.7 |
Safety Outcomes
Toxicity: total number of SAEs and other AEs (NCT00301808)
Timeframe: 72 hours after 2nd and 3rd cycles: 30 days after completion of study treatment; Every 2 months thereafter; then once a year
| Intervention | Adverse event (Number) |
|---|
| Serious (grade 3 or 4) | other (grade 0, 1, or 2) |
|---|
| Cisplatin, Docetaxel & Radiation Therapy | 20 | 245 |
Progression-free Survival
Progression-free survival using Kaplan-Meier estimates (NCT00301808)
Timeframe: Approximately 3 weeks after the last cycle of cisplatin/pemetrexed or completion of radiation whichever is the later.
| Intervention | months (Median) |
|---|
| Cisplatin, Docetaxel & Radiation Therapy | 16.9 |
Probability of Overall Survival at One Year
Overall Survival at one year using Kaplan-Meier product-limit analysis (NCT00301808)
Timeframe: at 1 year
| Intervention | probability of overall survival at 1 yr. (Number) |
|---|
| Cisplatin, Docetaxel & Radiation Therapy | 0.66 |
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
| Intervention | months (Median) |
|---|
| Enzastaurin/Pemetrexed/Carboplatin | 2.6 |
| Pemetrexed/Carboplatin | 3.8 |
| Docetaxel/Carboplatin | 2.6 |
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]
| Intervention | units 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 | -2.52 | 2.77 |
,| Pemetrexed/Carboplatin | -0.78 | -5.66 | -1.52 | -0.77 | -3.11 | -2.81 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Enzastaurin/Pemetrexed/Carboplatin | 9 |
| Pemetrexed/Carboplatin | 16 |
| Docetaxel/Carboplatin | 19 |
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
| Intervention | months (Median) |
|---|
| Enzastaurin/Pemetrexed/Carboplatin | 7.4 |
| Pemetrexed/Carboplatin | 9.3 |
| Docetaxel/Carboplatin | 5.8 |
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]
| Intervention | units 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 | -4.69 | 3.38 |
,| Enzastaurin/Pemetrexed/Carboplatin | -3.98 | -3.25 | 0.39 | 0.31 | 1.89 | 7.38 |
,| Pemetrexed/Carboplatin | 1.12 | -1.54 | 0.64 | 3.54 | -0.26 | -0.83 |
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
| Intervention | Participants (Count of Participants) |
|---|
| AEs | SAEs | Deaths Due to AEs |
|---|
| Docetaxel/Carboplatin | 69 | 26 | 4 |
,| Enzastaurin/Pemetrexed/Carboplatin | 63 | 35 | 3 |
,| Pemetrexed/Carboplatin | 70 | 20 | 5 |
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
| Intervention | months (Median) |
|---|
| Enzastaurin/Pemetrexed/Carboplatin | 4.6 |
| Pemetrexed/Carboplatin | 6.0 |
| Docetaxel/Carboplatin | 4.1 |
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
| Intervention | months (Median) |
|---|
| Enzastaurin/Pemetrexed/Carboplatin | 7.2 |
| Pemetrexed/Carboplatin | 12.7 |
| Docetaxel/Carboplatin | 9.2 |
Proportion of Patients With PSA Complete Response (CR) at 12 Months
PSA CR is defined as a PSA level less than 0.2 ng/ml measured for 2 consecutive measurements at least 4 weeks apart. Patients who met the criterion of PSA CR and had PSA level less than 0.2 ng/ml before and after the 12-month time point are considered as having a PSA CR at 12 months. (NCT00309985)
Timeframe: Assessed at 12 months
| Intervention | proportion of participants (Number) |
|---|
| Androgen-Deprivation Therapy and Docetaxel | 0.277 |
| Androgen-Deprivation Therapy Alone | 0.168 |
Proportion of Patients With PSA Complete Response (CR) at 6 Months
PSA CR is defined as a PSA level less than 0.2 ng/ml measured for 2 consecutive measurements at least 4 weeks apart. Patients who met the criterion of PSA CR and had PSA level less than 0.2 ng/ml before and after the 6-month time point are considered as having a PSA CR at 6 months. (NCT00309985)
Timeframe: Assessed at 6 months
| Intervention | proportion of participants (Number) |
|---|
| Androgen-Deprivation Therapy and Docetaxel | 0.320 |
| Androgen-Deprivation Therapy Alone | 0.196 |
Overall Survival
Overall survival is defined as the time from randomization to death or date last known alive. Survival data reflects the database as of December 23, 2013. (NCT00309985)
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; then annually if patient is 5 - 10 years from study entry
| Intervention | months (Median) |
|---|
| Androgen-Deprivation Therapy and Docetaxel | 57.6 |
| Androgen-Deprivation Therapy Alone | 44.0 |
Time to Castration Resistant Prostate Cancer (Hormone Refractory Disease)
Time to castration resistant prostate cancer is defined as the time from randomization to PSA progression or clinical progression, whichever occurred first. Patients without documented progression were censored at the date of last disease assessment. Secondary endpoint data reflect the database as of December 23, 2014. (NCT00309985)
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; then annually if patient is 5 - 10 years from study entry
| Intervention | months (Median) |
|---|
| Androgen-Deprivation Therapy and Docetaxel | 20.2 |
| Androgen-Deprivation Therapy Alone | 11.7 |
Time to Clinical Progression
Time to clinical progression is defined as the time from randomization to clinical progression. Clinical progression is defined as increasing symptomatic bone metastases, progression per Response Evaluation Criteria In Solid Tumors (RECIST) criteria or clinical deterioration due to cancer per investigator's opinion. Patients without documented clinical progression were censored at the date of last disease assessment. Secondary endpoint data reflect the database as of December 23, 2014. (NCT00309985)
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; then annually if patient is 5 - 10 years from study entry
| Intervention | months (Median) |
|---|
| Androgen-Deprivation Therapy and Docetaxel | 33.0 |
| Androgen-Deprivation Therapy Alone | 19.8 |
QOL Change From Baseline to 3 Months
The primary QOL change was evaluated by the Functional Assessment of Cancer Therapy - Prostate (FACT-P) instrument. FACT-P is a self-report measure of both general and disease-specific QOL. Higher scores represent better QOL. The FACT-P (version 4) contains 39 likert items distributed over 5 subscales: physical (7 items), social/family (7 items), emotional (6 items), and functional (7 items) well-being, and the additional concerns related to prostate cancer scale (12 items). The FACT-P total score is calculated by summing all these 5 subscales and ranges from 0 to 156. (NCT00309985)
Timeframe: Assessed at baseline and 3 months
| Intervention | units on a scale (Mean) |
|---|
| Androgen-Deprivation Therapy and Docetaxel | -2.7 |
| Androgen-Deprivation Therapy Alone | -1.1 |
Death From Any Cause (Overall Survival)
The considered event is death from any cause. The analysis is performed on the time from randomization to this event. The Measured Values table below presents the numbers of patients with the event at the end of the study period. (NCT00312208)
Timeframe: Median follow-up of 65 months
| Intervention | Participants (Number) |
|---|
| Doxorubicin + Cyclophosphamide Followed by Docetaxel (AC -> T) | 187 |
| Docetaxel + Doxorubicin and Cyclophosphamide (TAC) | 202 |
Disease Control Rate (DCR)
Disease control rate is defined as the number of patients who achieved disease control at least 6 weeks following randomisation. Disease control at 6 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 6 weeks as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere, PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions and SD >= 6 is assigned to patients who have not responded and have no evidence of progression at least 6 weeks after randomisation. (NCT00312377)
Timeframe: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
| Intervention | Participants (Number) |
|---|
| Vandetanib 100 mg Plus Docetaxel | 413 |
| Placebo Plus Docetaxel | 380 |
Duration of Response (DoR)
Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment) (NCT00312377)
Timeframe: RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
| Intervention | Weeks (Median) |
|---|
| Vandetanib 100 mg Plus Docetaxel | 29.9 |
| Placebo Plus Docetaxel | 19.7 |
Objective Response Rate (ORR)
The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) as determined according to RECIST 1.0. CR is defined as the disappearance of all target lesions with no evidence of tumour elsewhere and PR is defined as at least a 30% reduction in the total tumour size of measurable lesions with no new lesions and no progression in the non-target lesions. (NCT00312377)
Timeframe: Each patient was assessed for objective response from the sequence of RECIST scan data up to data cut off. RECIST tumour assessments carried out every 6 weeks from randomisation until objective progression
| Intervention | Participants (Number) |
|---|
| Vandetanib 100 mg Plus Docetaxel | 120 |
| Placebo Plus Docetaxel | 71 |
Overall Survival (OS) in the Overall Population
Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown). (NCT00312377)
Timeframe: Time to death in months
| Intervention | Months (Median) |
|---|
| Vandetanib 100 mg Plus Docetaxel | 10.6 |
| Placebo Plus Docetaxel | 10 |
Progression-Free Survival (PFS) in the Overall Population
Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions. (NCT00312377)
Timeframe: RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
| Intervention | Weeks (Median) |
|---|
| Vandetanib 100 mg Plus Docetaxel | 17.3 |
| Placebo Plus Docetaxel | 14 |
Progression-Free Survival (PFS) in the Female Population
Median time (in weeks) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. Progression was derived according to RECIST 1.0 and is defined as an increase of at least 20% in the total tumour size of measurable lesions over the nadir measurement, unequivocal progression in the non-target lesions or the appearance of one or more new lesions. (NCT00312377)
Timeframe: RECIST tumour assessments carried out every 6 weeks from randomisation until the date of first documented objective disease progression or date of death from any cause, whichever came first assessed up to 24 months
| Intervention | Weeks (Median) |
|---|
| Vandetanib 100 mg Plus Docetaxel | 20.1 |
| Placebo Plus Docetaxel | 18.3 |
Overall Survival (OS) in the Female Population
Overall survival is defined as the time from date of randomization until death. Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive (ie their status must be known at the censored date and should not be lost to follow up or unknown). (NCT00312377)
Timeframe: Time to death in months
| Intervention | Months (Median) |
|---|
| Vandetanib 100 mg Plus Docetaxel | 12.7 |
| Placebo Plus Docetaxel | 14.2 |
Total Number of Circulation Tumor Cells (CTCs)
Blood samples were collected and processed to enumerate the number of total CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive epithelial cell adhesion molecule (EpCAM) and cytokeratin staining. (NCT00313781)
Timeframe: Baseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose)
| Intervention | Number of CTCs/7.5 mL (Mean) |
|---|
| Baseline (Cycle 1 Day 1) (n=46, 39) | Cycle 3 Day1 (n=28, 29) | Cycle 5 Day 1 (n=25, 23) |
|---|
| CP-751,871+Docetaxel+Prednisone | 105.17 | 6.39 | 15.20 |
,| Docetaxel+Prednisone | 213.23 | 12.21 | 17.78 |
Total Number of the Insulin Like Growth Factor Receptor Type 1 (IGF-1R) Positive CTCs
Blood samples were collected to enumerate the number of total IGF-1R positive CTCs via Veridex CellSearch technology in which CTCs were identified based on cell surface positive EpCAM and cytokeratin staining. A separate CellSave tube of cells was also collected and processed with cell surface staining of IGF-1R to enumerate surfaces of IGF-1R-positive CTCs. (NCT00313781)
Timeframe: Baseline, prior to dosing in odd numbered cycles (ie. Cycle 1, 3, 5, etc) and end of treatment (up to 28 days post last dose)
| Intervention | Number of IGF-1R positive CTCs/7.5 mL (Mean) |
|---|
| Baseline (Cycle 1 Day 1) (n=22, 18) | Cycle 3 Day1 (n=12, 15) | Cycle 5 Day 1 (n=11, 10) |
|---|
| CP-751,871+Docetaxel+Prednisone | 24.73 | 2.33 | 2.00 |
,| Docetaxel+Prednisone | 54.94 | 4.93 | 3.90 |
Human Anti-human Antibody (HAHA) at Baseline (Day 1 of Cycle 1)
Levels of HAHA in serum were detected at baseline. (NCT00313781)
Timeframe: Baseline (Day 1 of Cycle 1)
| Intervention | mg/deciliter (dl) (Mean) |
|---|
| CP-751,871+Docetaxel+Prednisone | 1130.3 |
| Docetaxel+Prednisone | 1338.1 |
Human Anti-human Antibody (HAHA) at the Last Follow-up Visit
Levels of HAHA in serum were detected at the last follow-up visit. (NCT00313781)
Timeframe: The last follow-up visit (150 days post last dose)
| Intervention | mg/dl (Mean) |
|---|
| CP-751,871+Docetaxel+Prednisone | 944.81 |
| Docetaxel+Prednisone | 819.00 |
| Docetaxel+Prednisone+CP-751,871 Crossover | 970.86 |
Percentage of Participants With Prostate Specific Antigen (PSA) Best Response
Percentage of participants with PSA best response of either PSA normalization (PN) or partial PSA response (PR) relative to the total number of participants evaluable for response. PN was defined as PSA =< 0.2 nanogram/milliliter (ng/ml) on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression. PP was defined as >= 50% decrease in PSA from baseline on 2 successive evaluations at least 3 weeks apart and no imaging or clinical evidence of disease progression. (NCT00313781)
Timeframe: Baseline, Day 1 and Day 15 of each cycle, end of treatment (up to 28 days post last dose) and follow-up (monthly, up to 150 days post last dose)
| Intervention | Percentage of participants (Mean) |
|---|
| CP-751,871+Docetaxel+Prednisone | 51.7 |
| Docetaxel+Prednisone | 60.2 |
| Docetaxel+Prednisone+CP-751,871 Crossover | 28.1 |
Progression Free Survival (PFS)
PFS was defined as the time from randomization to first event of disease progression. Disease progression events were defined as the following: PSA progression,objective disease progression as per RECIST, death, and discontinuation of treatment due to symptomatic deterioration. PSA progression was defined as the time-point of PSA progression on 2 successive evaluations taken 1 week apart after dosing in cycle 3. (NCT00313781)
Timeframe: Baseline, Day 15 of each cycle and follow-up (monthly, up to 150 days post last dose)
| Intervention | Months (Median) |
|---|
| CP-751,871+Docetaxel+Prednisone | 4.9 |
| Docetaxel+Prednisone | 7.7 |
| Docetaxel+Prednisone+CP-751,871 Crossover | 4.0 |
Maximum Tolerated Dose (MTD)
MTD will be the dose at which 1 or fewer patients (≤ 1/6) experiences a DLT during the first or second cycle with the next higher dose having at least 2/3 or 2/6 patients experiencing Dose Limiting Toxicities (DLT). (NCT00320749)
Timeframe: Weekly up to 24 weeks
| Intervention | mg/m^2 (Number) |
|---|
| docetaxel | gemcitabine | capecitabine |
|---|
| Capecitabine, Docetaxel, Gemcitabine | 36 | 750 | 625 |
Therapeutic 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. (NCT00320749)
Timeframe: every 8 weeks, up to 24 weeks
| Intervention | percent of patients (Number) |
|---|
| Partial Response | Complete Response | Stable Disease |
|---|
| Capecitabine, Docetaxel, Gemcitabine | 11 | 0 | 72 |
Common Toxicities
The NCI Common Terminology Criteria for Adverse Events version 3.0 was used for adverse event reporting and toxicity grading. (NCT00320749)
Timeframe: Weekly up to 24 weeks
| Intervention | percent of patients (Number) |
|---|
| leukopenia | neutropenia | fatigue |
|---|
| Capecitabine, Docetaxel, Gemcitabine | 29 | 29 | 25 |
Endorectal MRI Response After Completion of 6 Cycles of Neoadjuvant Therapy
A response was defined as a decrease in tumor size of >50% for the largest lesion in the prostate by endorectal MRI. (NCT00321646)
Timeframe: after 6 months of neoadjuvant chemotherapy.
| Intervention | proportion of participants (Number) |
|---|
| Chemotherapy | 0.29 |
PSA Response After Completing 6 Cycles of Neoadjuvant Chemotherapy.
The rate of PSA decline by 50% compared to baseline PSA. (NCT00321646)
Timeframe: after 6 months of ajuvant chemotherapy.
| Intervention | proportion of participants (Number) |
|---|
| Chemotherapy | 0.22 |
Prostate-specific Antigen Short-term Response Rate Measured as a Percentage Change in PSA
"All participants were combined for this assessment as pre-specified in the protocol.~The percentage change for patients were determined from pre- and post- treatment PSA values. The mean percentage change in PSA will be reported.~PSA will be monitored every 3-6 months during the first 5 years, then annually after surgery for up to 10 years" (NCT00321698)
Timeframe: Baseline (pre-treatment) and 1 month after surgery (post-treatment)
| Intervention | percentage change (Mean) |
|---|
| All Research Participants | -49.1 |
Pathologic Response Rate at the Phase II Dose
"Pathologic response rate is determined post-prostatectomy by pathologist laboratory analyses. The TNM system is the most widely used cancer staging system. Most hospitals and medical centers use the TNM system as their main method for cancer reporting. In the TNM system:~The T refers to the size and extent of the main/primary tumor. T1, T2, T3, T4: Refers to the size and/or extent of the main tumor. The higher the number after the T, the larger the tumor or the more it has grown into nearby tissues. T's may be further divided to provide more detail, such as T3a and T3b." (NCT00321698)
Timeframe: 4-6 weeks after study treatment
| Intervention | participants (Number) |
|---|
| Pathologic Stage pT2c | Pathologic Stage pT3a | Pathologic Stage pT3b |
|---|
| Phase II MTD Dose | 7 | 3 | 3 |
Surgical Margin Status at Time of Prostatectomy (Count of Subjects With Negative Surgical Margins)
"Pathologic response rate is determined post-prostatectomy by pathologist laboratory analyses. The TNM system is the most widely used cancer staging system. Most hospitals and medical centers use the TNM system as their main method for cancer reporting. In the TNM system:~The M refers to whether the cancer has metastasized. This means that the cancer has spread outside of the primary tumor to other parts of the body." (NCT00321698)
Timeframe: 5 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Phase I Dose 1-4 | 9 |
| Phase II MTD Dose | 13 |
Clinical Progression-free Rate as Determined by <0.1ng PSA Results
The estimated percentage of participants who were progression-free at 5 years per analyses of PSA results post-study treatment. (NCT00321698)
Timeframe: 3, 6, 9, 12 months and annually, up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| All Research Participants | 62.8 |
Maximum Tolerated Dose (MTD)
"Maximal tolerated dose (MTD) of the combination radiation (45 Gy) and docetaxel.~The dose of radiation will be fixed at 45 Gy while the dose of docetaxel will be escalated. The starting dose of docetaxel will be 10 mg/m2 and will be escalated in increments of 10 mg/m2 up to a dose of 30 mg/m2 the pre-planned ceiling).~MTD will be the dose that is associated with no more than 1 dose limiting toxicity (DLT) up to 6 patients. The DLT will be defined as clinically significant grade 3 non-hematologic or grade 4 hematologic toxicity, attributable to the chemoirradiation. If 2 of 3 patients experience a DLT, dose escalation will stop and the previous dose level will be considered the MTD. If 1 of 3 has DLT, additional 3 patients will be enrolled at the same dose level. If none of the additional 3 patients has DLT, the dose escalation will continue. If 1 additional patient has DLT, the previous dose will be considered the MTD and dose escalation will be stopped." (NCT00321698)
Timeframe: 5 weeks
| Intervention | mg/m^2 (Number) |
|---|
| Phase I Dose 1-4 | 30 |
Overall Survival
Overall survival (OS) was defined as the time from randomization to death from any cause, and patients who were thought to be alive at the time of final analysis were censored at the last date of contact. The study failed to meet its primary endpoint. (NCT00324805)
Timeframe: From registration to death, up to 10 years
| Intervention | months (Median) |
|---|
| Arm I (Chemotherapy) | NA |
| Arm II (Chemotherapy, Bevacizumab) | 85.8 |
Disease-free Survival
Disease-free survival (DFS) was defined as the time from randomization to an event. Events include disease recurrence, new primary of lung cancer, second primaries or death, whichever occurred first; however, it should be noted that patients with new primaries at other non-lung sites should have continued followup for recurrence of the original cancer. Patients that have not had an event reported at analysis were censored at their last date of disease assessment. (NCT00324805)
Timeframe: From registration to death, up to 10 years
| Intervention | months (Median) |
|---|
| Arm I (Chemotherapy) | 42.9 |
| Arm II (Chemotherapy, Bevacizumab) | 40.6 |
Safety and Tolerability of Custirsen (OGX-011) in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second-line Chemotherapy.
"Safety and tolerability were based on Adverse Events (AE) and Serious Adverse Events (SAE) graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE).~The CTCAE has 5 grades 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; and Grade 5=Death related to AE." (NCT00327340)
Timeframe: Subjects were followed for safety from enrollment for up to 8 months (9 three-week cycles plus 30 days after end of treatment)
| Intervention | percentage of participants (Number) |
|---|
| Percent of Subjects with Serious Adverse Events | Percent of Subjects with Grade 5 Adverse Events | Percent of Subjects with Grade 4 Adverse Events | Percent of Subjects with Grade 3 Adverse Events | Percent of Subjects with Grade 2 Adverse Events | Percent of Subjects with Grade 1 Adverse Events | Percent of Subjects who Discontinued Study Drug |
|---|
| OGX-011 + Docetaxel + Prednisone | 26 | 4 | 15 | 52 | 98 | 100 | 17 |
,| OGX-011 + Mitoxantrone + Prednisone | 26 | 13 | 26 | 70 | 83 | 100 | 22 |
Relationship Between Changes in Serum Clusterin Levels and Change in Serum PSA Levels When OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone is Administered as Second Line Chemotherapy.
Serum clusterin samples were collected prior to receiving OGX-011 loading dose 1, prior to study treatment on Day 1 of each cycle, and at the end of treatment. PSA was evaluated at screening, on Day 1 of each cycle, at the end of treatment visit, and during off-treatment follow-up. PSA response was defined in the protocol as a decrease in PSA of ≥ 50% relative to baseline on two or more consecutive measurements 4-6 weeks apart. (NCT00327340)
Timeframe: Enrollment until disease progression (up to 13 months)
| Intervention | percentage of participants (Number) |
|---|
| Minimum clusterin level < or = to 45 mcg/mL | Minimum clusterin level > 45 mcg/mL |
|---|
| OGX-011 + Docetaxel + Prednisone | 24 | 7 |
,| OGX-011 + Mitoxantrone + Prednisone | 22 | 4 |
Feasibility of Treatment With OGX-011 in Combination With Either Docetaxel/Prednisone or Mitoxantrone/Prednisone as Second Line Chemotherapy Based on Time to Pain Progression
Time to pain progression was defined as the time (months) from the first dose of OGX-011 to the first documentation of pain or analgesic progression or initiation of palliative radiation therapy. Pain response was defined as either a decrease of at least two points on the 11-point Worst Pain Scale, without an increase in analgesic level, maintained for at least two consecutive measurements approximately three weeks apart -or- a decrease in analgesic level, without an increase in pain score, maintained for at least two consecutive measurements approximately three weeks apart. (NCT00327340)
Timeframe: Enrollment until pain progression (up to 21 months)
| Intervention | months (Number) |
|---|
| OGX-011 + Mitoxantrone + Prednisone | 5.2 |
| OGX-011 + Docetaxel + Prednisone | 7.2 |
Feasibility of Treatment With Custirsen (OGX-011) in Combination With Second-line Chemotherapy Based on Prostate Specific Antigen (PSA) Response
PSA or prostate specific antigen is a marker for prostate cancer. A PSA response was defined as a decrease in PSA values of ≥ 50% relative to baseline on two or more consecutive measurements that were 4-6 weeks apart. (NCT00327340)
Timeframe: PSA was evaluated at screening, on Day 1 of each cycle, at the end of treatment visit and during off-treatment follow up (up to 27 months)
| Intervention | percentage of participants (Number) |
|---|
| OGX-011 / Mitoxantrone/Prednisone | 17 |
| OGX-011 / Docetaxel/Prednisone | 31 |
Objective Response Rate as Measured by RECIST Criteria
Objective response rate as measured by RECIST criteria (NCT00331682)
Timeframe: Up to 2 years
| Intervention | participants (Number) |
|---|
| Stable Disease | Progression of Disease |
|---|
| Docetaxel and Flavopiridol | 3 | 6 |
Overall Survival
Will be computed using Kaplan-Meier methods. (NCT00331682)
Timeframe: Between the start of treatment until patient death, assessed up to 2 years
| Intervention | months (Median) |
|---|
| Docetaxel and Flavopiridol | 4.2 |
Time to Progression
Will be computed using Kaplan-Meier methods. (NCT00331682)
Timeframe: Between the start of treatment until the criteria for progression are met, assessed up to 2 years
| Intervention | weeks (Median) |
|---|
| Docetaxel and Flavopiridol | 8 |
Progression-free Survival
Progression-free survival was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST 1.0). Progression-free survival was defined as the time from randomization to the time of the first documented disease progression or death, whichever occurred first. Disease progression was defined as ≥ 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 unequivocal progression of existing non-target lesions, or appearance of new lesion(s). (NCT00333775)
Timeframe: Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months)
| Intervention | Months (Median) |
|---|
| Docetaxel 100 mg/m^2 Plus Placebo | 8.0 |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 7.5 mg/kg | 8.7 |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 15.0 mg/kg | 8.8 |
Time to Treatment Failure
Time to treatment failure was defined as time from randomization to the date of disease progression, death, or withdrawal of treatment due to an adverse event, withdrawal of informed consent, insufficient therapeutic response, refusal of treatment/failure to co-operate, or failure to return, whichever occurred first. (NCT00333775)
Timeframe: Baseline to the 15 September 2008 cut-off date (up to 2 years, 6 months)
| Intervention | months (Median) |
|---|
| Docetaxel 100 mg/m^2 Plus Placebo | 6.1 |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 7.5 mg/kg | 7.0 |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 15.0 mg/kg | 7.7 |
Percentage of Participants With a Complete Response or a Partial Response
Responses were evaluated using the Response Evaluation Criteria in Solid Tumors. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. (NCT00333775)
Timeframe: Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months)
| Intervention | Percentage of participants (Number) |
|---|
| Complete response | Partial response |
|---|
| Docetaxel 100 mg/m^2 Plus Bevacizumab 15.0 mg/kg | 1.0 | 62.1 |
,| Docetaxel 100 mg/m^2 Plus Bevacizumab 7.5 mg/kg | 3.0 | 52.2 |
,| Docetaxel 100 mg/m^2 Plus Placebo | 1.0 | 43.5 |
Overall Survival
Overall survival was defined as the time from randomization to death from any cause. (NCT00333775)
Timeframe: Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months)
| Intervention | Months (Median) |
|---|
| Docetaxel 100 mg/m^2 Plus Placebo | NA |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 7.5 mg/kg | NA |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 15.0 mg/kg | NA |
Duration of Response
Duration of response was defined as the time from the first documented complete response or partial response to disease progression or death. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. Responses were evaluated using the Response Evaluation Criteria in Solid Tumors. (NCT00333775)
Timeframe: Baseline to the 15 September 2008 cut-off date (up to 2 years, 6 months)
| Intervention | Months (Median) |
|---|
| Docetaxel 100 mg/m^2 Plus Placebo | 6.4 |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 7.5 mg/kg | 7.2 |
| Docetaxel 100 mg/m^2 Plus Bevacizumab 15.0 mg/kg | 7.0 |
Overall Survival
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. (NCT00334815)
Timeframe: Every week, up to 4 years
| Intervention | Months (Median) |
|---|
| Low Risk Patient Stratum | 46 |
| High Risk Patient Stratum | 17 |
Progression-free Survival
From date of registration to time of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact. (NCT00334815)
Timeframe: Disease assessments were performed every 10 weeks as long as the patient remained on protocol treatment, up to 4 years.
| Intervention | Months (Median) |
|---|
| Low Risk Patient Stratum | 38 |
| High Risk Patient Stratum | 15 |
Response Rate (Confirmed or Unconfirmed Partial Response)
Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. (NCT00334815)
Timeframe: Response assessment occured at the end of CRT and docetaxel/bevacizumab and then every 2-3 months for 2 years and then every 6 months until 4 years after the initial registration
| Intervention | percentage of participants (Number) |
|---|
| Low Risk Patient Stratum | 64 |
| High Risk Patient Stratum | 70 |
Adverse Events
Only adverse events that are possibly, probably or definitely related to study drug are reported. (NCT00334815)
Timeframe: Up to one year
| Intervention | Participants (Number) |
|---|
| Acidosis (metabolic or respiratory) | Arthritis (non-septic) | Calcium, serum-low (hypocalcemia) | Carbon monoxide diffusion capacity (DL(co)) | Creatinine | Dehydration | Dyspnea (shortness of breath) | Esophagitis | FEV(1) | Febrile neutropenia | Glucose, serum-high (hyperglycemia) | Hemoglobin | Hemorrhage, Respiratory tract NOS | Hemorrhage, GI - Peritoneal cavity | Hemorrhage, pulmonary/upper respiratory - Lung | Hypotension | Hypoxia | INR (of prothrombin time) | Inf (clin/microbio) w/Gr 3-4 neuts - Nose | Inf (clin/microbio) w/Gr 3-4 neuts - Oral cav-gums | Inf (clin/microbio) w/Gr 3-4 neuts - UTI | Inf (clin/microbio) w/Gr 3-4 neuts - Upper airway | Inf w/normal ANC or Gr 1-2 neutrophils - Blood | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | Leukocytes (total WBC) | Lymphopenia | Muscle weakness, not d/t neuropathy - body/general | Nausea | Neutrophils/granulocytes (ANC/AGC) | Pain - Chest wall | Pain - Chest/thorax NOS | Pain - Head/headache | Pain - Joint | Pain - Neck | Pain - Throat/pharynx/larynx | Platelets | Pneumonitis/pulmonary infiltrates | Potassium, serum-low (hypokalemia) | Pulmonary/Upper Respiratory-Other (Specify) | Rash/desquamation | Rash: dermatitis associated w/radiation | Sodium, serum-low (hyponatremia) | Weight loss |
|---|
| Concurrent Chemotherapy and Radiotherapy | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 1 | 3 | 1 | 2 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 6 | 2 | 1 | 2 | 10 | 1 | 1 | 1 | 0 | 1 | 1 | 2 | 1 | 3 | 0 | 1 | 1 | 1 | 0 |
,| Consolidation Therapy With Docetaxel and Bevacizumab. | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 1 |
Tumor Response as Measured by Ultrasound
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. (NCT00343512)
Timeframe: At screening, 8 weeks and at surgery (within 14-21 days)
| Intervention | participants (Number) |
|---|
| Complete Response | Progressive Disease | Stable Disease | Partial Response |
|---|
| Therapeutic Intervention | 5 | 1 | 1 | 11 |
Safety Profile Based on Number of Patients With Each Worst-grade Toxicity
Not all participants necessarily have an adverse event, thus not everyone will be accounted for in worst-grade toxicities. Likewise, one participant can potentially have more than one event in various grades 1-5 which accounts for the difference in number of patients analyzed and total number in the worst-grade toxicity tables. Tables represent the number of patients with worst-grade toxicity at each of five grades (grade 1, least severe; to grade 5, most severe) following NCI Common Toxicity Criteria (NCT00343512)
Timeframe: Through 30 days after completion of treatment
| Intervention | participants (Number) |
|---|
| No. patients with worst-grade toxicity 1 | No. patients with worst-grade toxicity 2 | No. patients with worst-grade toxicity 3 | No. patients with worst-grade toxicity 4 | No. patients with worst-grade toxicity 5 |
|---|
| Therapeutic Intervention | 5 | 8 | 11 | 1 | 0 |
Number Participants to Achieve Pathologic Complete Response
whether or not patient has pathologic complete response (pCR) to dose dense docetaxel in the neoadjuvant setting (pCR = no residual viable tumor on histologic analysis) (NCT00343512)
Timeframe: 3 month
| Intervention | participants (Number) |
|---|
| pCR: Yes | pCR: No |
|---|
| Therapeutic Intervention | 5 | 29 |
Rate of Prostate-Specific Antigen (PSA) Decline Reported as the Number of Subjects Reaching a PSA Nadir of Zero Following the Intervention.
Subjects were followed after the intervention and monitored for PSA (Prostate Specific Antigen) decline for up to 5 years of follow-up, to determine how many had a decline and reached a PSA nadir of zero.. (NCT00348816)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel (Single Arm) | 12 |
Progression-free Survival Based on PSA Progression
Subjects were monitored for PSA (Prostate Specific Antigen) for up to 5 years of follow-up. (NCT00348816)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel (Single Arm) | 12 |
Number of Participants With Grade 3 or Higher Toxicity
summary of grade 3 (per Common Toxicity Criteria) or higher toxicities which generally is described as a severe adverse reaction or symptom. (NCT00354601)
Timeframe: Days 1, 8, 15, 21 of each course and treatment end (28 days after last dose or start of new therapy)
| Intervention | participants (Number) |
|---|
| Docetaxel and Capecitabine | 1 |
Progression-free Survival (PFS)
"PFS was defined as the interval from the date of registration to the earliest date of documented evidence of progressive disease, or the date of death due to any cause, whichever occurred first.~Progressive disease occurred when the participant had at least a 20% increase in the sum of the longest diameter (LD) of target lesions, compared to the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions." (NCT00356122)
Timeframe: Baseline to PFS (up to 24 months after the first treatment)
| Intervention | Months (Median) |
|---|
| Docetaxel/Oxaliplatin/Bevacizumab | 5.6 |
Time-to-treatment Failure (TTF)
"Treatment failure was defined as an event which lead to the participant's withdrawal from the study treatment due to lack of efficacy, disease progression, adverse events, or due to a participant's request as recorded in the Case Report Form (CRF), death, or use of other anticancer therapy.~TTF was assessed using Kaplan-Meier method, and the median TTF with 95% CIs was computed using the Brookmeyer and Crowley method." (NCT00356122)
Timeframe: Baseline to treatment failure (up to 24 months after the first treatment)
| Intervention | Months (Median) |
|---|
| Docetaxel/Oxaliplatin/Bevacizumab | 4.7 |
Objective Response Rate
"Objective response rate is the percentage of participants with an objective response. Improvements in tumor measurements from baseline values were assigned a status of Complete Response (CR) or Partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST). Overall objective response was the sum of CR and PR.~CR referred to the disappearance of all target lesions, and PR was at least 30% decrease in the sum of the longest diameter (LD) of target lesions, compared to the baseline sum LD. Responses were confirmed by repeat assessments within 4 to 6 weeks." (NCT00356122)
Timeframe: Baseline to CR or PR (up to 24 months after the first treatment)
| Intervention | Percentage of participants (Mean) |
|---|
| Docetaxel/Oxaliplatin/Bevacizumab | 30.2 |
Overall Survival (OS)
OS was measured from the date of registration to the date of death due to any cause, or to the date of last contact (for censored observations). OS was assessed by the Kaplan-Meier method and the estimates of median survival time with 95% CI are reported. (NCT00356122)
Timeframe: Baseline to OS (up to 24 months after the first treatment)
| Intervention | Months (Median) |
|---|
| Docetaxel/Oxaliplatin/Bevacizumab | 14.0 |
Disease Control Rate
Disease control rate was defined as the rate of partial response (PR) plus stable disease (SD; for at least 2 cycles). (NCT00362882)
Timeframe: Up to 4 years
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 50 |
| Arm 2 | 49 |
Progression-free Survival @ 6 Months
Estimated using the product-limit method of Kaplan and Meier. 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. (NCT00362882)
Timeframe: 6 months
| Intervention | percent of participants (Number) |
|---|
| Arm 1 | 30 |
| Arm 2 | 17 |
Overall Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT, MRI or X-ray: 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 (NCT00362882)
Timeframe: Up to 4 years
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 10 |
| Arm 2 | 10 |
Overall Survival
Will be estimated using the product-limit method of Kaplan and Meier. (NCT00362882)
Timeframe: From first day of treatment to time of death due to any cause, up to 4 years
| Intervention | Months (Median) |
|---|
| Arm 1 | 13.3 |
| Arm 2 | 7.8 |
Confirmed Overall Response (OR) Based on RECIST Criteria
"Confirmed OR was confirmed Complete Response (CR) + confirmed Partial Response (PR). According to RECIST~CR was the disappearance of all tumor lesions~PR was a pre-defined decrease in the size of tumor lesions.~To determine a response, radiologic tumors assessments were performed using computed tomography (CT) and/or magnetic resonance imaging (MRI) of the chest, and the abdomen, bone scan or positron emission tomography (PET) scan, and other imaging techniques as clinically indicated. To confirm a response, 2 assessments separated by 28 days or more were required." (NCT00364611)
Timeframe: From treatment initiation to June 2011
| Intervention | participants (Number) |
|---|
| Confirmed overall response | Confirmed complete response | Confirmed partial response |
|---|
| Docetaxel and Bevacizumab | 30 | 3 | 27 |
,| Docetaxel, Bevacizumab and Trastuzumab | 17 | 4 | 13 |
Overall Survival (OS) Time
"OS was the interval between the date of study entry and the date of death from any cause. In the absence of confirmation of death, survival time was censored at the last date the participant was known to be alive.~OS time was estimated from Kaplan-Meier Plots." (NCT00364611)
Timeframe: From treatment initiation to June 2011
| Intervention | days (Median) |
|---|
| Docetaxel and Bevacizumab | 750 |
| Docetaxel, Bevacizumab and Trastuzumab | 986 |
Time to Progression-free Survival (PFS)
"Time to PFS was the interval from the date of registration to the earliest of the following documented dates:~PD as defined by RECIST (criteria pre-defining changes in lesion size or appearance)~symptomatic deterioration~death.~Time to PFS was estimated from Kaplan-Meier Plots." (NCT00364611)
Timeframe: From treatment initiation to PFS event (up to June 2011)
| Intervention | days (Median) |
|---|
| Docetaxel and Bevacizumab | 255 |
| Docetaxel, Bevacizumab and Trastuzumab | 403 |
Number of Participants With Adverse Events (AE)
"An adverse event (AE) was any unfavorable and unintended sign, symptom, syndrome, or illness that developed or worsened during the clinical study. AEs occurring on or after first dose of study medication inclusive to 30 days post-last dose were the treatment emergent adverse events (TEAEs).~An serious adverse event was an AE that at any dose (including overdose) resulted in death, was life-threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly, and/or was medically important." (NCT00364611)
Timeframe: From treatment initiation to 30 days after the last dose of study treatment
| Intervention | participants (Number) |
|---|
| with treatment emergent adverse events (TEAEs) | with serious adverse events | with TEAEs resulting in death |
|---|
| Docetaxel and Bevacizumab | 52 | 14 | 3 |
,| Docetaxel, Bevacizumab and Trastuzumab | 20 | 4 | 0 |
Number of Participants With Confirmed Clinical Benefit Based on RECIST Criteria
"Clinical Benefit (CB) was achieved in participants with a response (CR + PR) or a stable disease (SD).~According to RECIST~CR was the disappearance of all tumor lesions~PR was a pre-defined decrease in the size of tumor lesions~SD was neither sufficient decrease in tumor size to qualify for PR or sufficient increase to qualify for PD.~Confirmation of a response needed 2 responses scored, separated by 28 days or more (for CR and PR), and by 26 weeks or more (for SD)." (NCT00364611)
Timeframe: From treatment initiation to June 2011
| Intervention | participants (Number) |
|---|
| with confirmed Clinical Benefit (CR+PR+SD) | with confirmed CR | with confirmed PR | with confirmed SD |
|---|
| Docetaxel and Bevacizumab | 35 | 3 | 27 | 14 |
,| Docetaxel, Bevacizumab and Trastuzumab | 17 | 4 | 13 | 1 |
Progression-free Survival (PFS) Rate: Percentage of Participants With PFS
"PFS was the time from registration to first documentation of~progressive disease (PD) based on Response Evaluation Criteria in Solid Tumors (RECIST) - criteria pre-defining changes in lesion size or appearance~symptomatic deterioration~death due to any cause (in absence of PD).~The Percentage of participants with PFS is reported.~For the analysis, participants were censored~on the last available tumor assessment date on study treatment if they~had no PFS event~were on anticancer therapy not related to study treatment~on the registration date if they~did not receive study drug~had no post baseline tumor assessment" (NCT00364611)
Timeframe: Up to 6 months and 12 months after treatment initiation
| Intervention | percentage of participants (Number) |
|---|
| PFS rate at 6 months | PFS rate at 12 months |
|---|
| Docetaxel and Bevacizumab | 59.6 | 30.8 |
,| Docetaxel, Bevacizumab and Trastuzumab | 90.5 | 81.0 |
Duration of Response (DR)
"DR was the interval from date of initial documented confirmed response (CR or PR) to the first documented confirmed date of disease progression (PD) or death from any cause in the absence of previous documentation of objective tumor progression.~Participants who were alive and without any record of PD at the time of discontinuation were censored at the last available tumor assessment date; participants with non-study anti-cancer therapy during the study were censored at the last available tumor assessment date prior to the anti-cancer therapy.~DR was estimated from Kaplan-Meier Plots." (NCT00364611)
Timeframe: From treatment initiation to June 2011
| Intervention | days (Median) |
|---|
| Docetaxel and Bevacizumab | 232 |
| Docetaxel, Bevacizumab and Trastuzumab | 366 |
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)
| Intervention | participants (Number) |
|---|
| Stratum 1 (AC->T + Bevacizumab) | 1 |
| Stratum 2 (TAC + Bevacizumab) | 3 |
| Stratum 3 (TCH + Bevacizumab).) | 1 |
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.
| Intervention | participants (Number) |
|---|
| with TEAE | with serious TEAE | with any TEAE leading to death | with any TEAE leading to treatment discontinuation | with any Grade 3-4 Serious TEAE |
|---|
| Stratum 1 (AC->T + Bevacizumab) | 78 | 23 | 0 | 21 | 23 |
,| Stratum 2 (TAC + Bevacizumab) | 75 | 24 | 2 | 24 | 24 |
,| Stratum 3 (TCH + Bevacizumab).) | 59 | 12 | 0 | 16 | 9 |
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
| Intervention | percentage of participants (Number) |
|---|
| DFS rate at 12 months | DFS rate at 24 months | DFS rate at 36 months |
|---|
| Stratum 1 (AC->T + Bevacizumab) | 93.6 | 87.1 | 85.5 |
,| Stratum 2 (TAC + Bevacizumab) | 95.9 | 94.1 | 90.4 |
,| Stratum 3 (TCH + Bevacizumab).) | 98.2 | 96.3 | 90.4 |
Reported Adverse Events
Number of Adverse Events (NCT00365417)
Timeframe: Approximately 14 months
| Intervention | events (Number) |
|---|
| Neoadjuvant Study Treatment | 566 |
Number of Patients With at Least One Surgical Complications (Wound Dehiscence, Infection, Seroma, or Hematoma).
Number of patients with at least one surgical complications (wound dehiscence, infection, seroma, or hematoma) (NCT00365417)
Timeframe: Two (2) years
| Intervention | participants (Number) |
|---|
| Chemo Plus Bevacizumab | 24 |
Overall Survival
Percentage of patients alive. (NCT00365417)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| Chemo Plus Bevacizumab | 74.52 |
Progression-free Survival
Percentage of patients free from disease progression. Progression is determined using international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. At least a 20% increase in the sum of the longest diameter of the target lesions. Other manifestations of progressive disease would also be classified as disease progression, eg., appearance of one or more new lesions in the breast, regional lymph nodes or distant sites, unequivocal progression of existing non-target lesions, and appearance of inflammatory carcinoma on clinical exam. (NCT00365417)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| Chemo Plus Bevacizumab | 57.69 |
Clinical Response Rate (cRR) of the Sequential Regimen
Clinical tumor measurements were required before study entry & before cycle 5 of chemotherapy (between AC & TX). Final tumor measurements were obtained 4-5 weeks after the last dose of chemotherapy. Clinical tumor assessments by physical examination were recommended before each chemotherapy cycle. The criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee(RECIST) were used to define clinical response status. CR was defined as the disappearance of all lesions with no evidence of PD. PR was defined as at least 30% decrease in the sum of the longest diameter of target lesions, using as reference the baseline sum longest diameter and/or the persistence of greater than or equal to 1 nontarget lesion without worsening of any other clinical manifestations of disease. PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, the appearance of new lesions, or unequivocal progression of existing lesions. (NCT00365417)
Timeframe: Approximately 6 months
| Intervention | percentage of patients (Number) |
|---|
| Chemo Plus Bevacizumab | 77.27 |
Cardiac Events
Events: Congestive Heart Failure; Cardiac Death (NCT00365417)
Timeframe: Assessments throughout; up to 18 months following study entry
| Intervention | cardiac events (Number) |
|---|
| Chemo Plus Bevacizumab | 0 |
pCR in the Breast and Nodes
Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel nodes (NCT00365417)
Timeframe: Approximately 7 months
| Intervention | participants (Number) |
|---|
| pCR in the breast and nodes | No pCR in the breast and nodes | No data available |
|---|
| Neoadjuvant Study Treatment | 4 | 38 | 3 |
Pathologic Complete Response (pCR) in the Breast
Measured by no histologic evidence of invasive tumor cells in the surgical breast specimen (NCT00365417)
Timeframe: Approximately 7 months
| Intervention | participants (Number) |
|---|
| pCR in the breast | No pCR in the breast | No data available |
|---|
| Neoadjuvant Study Treatment | 4 | 38 | 3 |
Duration of Response (DR)
Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cancer. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. (NCT00372424)
Timeframe: Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)
| Intervention | weeks (Median) |
|---|
| Sunitinib + Docetaxel + Trastuzumab | 51.3 |
Percentage of Participants With Objective Response (OR)
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). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response. CR are defined as disappearance of all target lesions. 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. (NCT00372424)
Timeframe: Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)
| Intervention | percentage of participants (Number) |
|---|
| Sunitinib + Docetaxel + Trastuzumab | 72.7 |
Maximum Observed Plasma Concentration (Cmax) of Docetaxel
Concentration values below the lower limit of quantification were taken as zero. (NCT00372424)
Timeframe: End of infusion (1 H) on Day 1 of Cycle 1, 2, 4 and 6
| Intervention | ng/mL (Mean) |
|---|
| Cycle1/Day1 (n= 23) | Cycle2/Day1 (n= 19) | Cycle4/Day1 (n= 16) | Cycle6/Day1 (n= 15) |
|---|
| Sunitinib + Docetaxel + Trastuzumab | 1117.05 | 1388.63 | 1316.88 | 1670.40 |
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A 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 are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. (NCT00372424)
Timeframe: From screening until 28 days post last dose of study drug
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| Sunitinib + Docetaxel + Trastuzumab | 24 | 11 |
Progression-free Survival (PFS)
"Time in weeks from start of study treatment to first documentation of objective tumor progression or death due to any cause. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7. 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)." (NCT00372424)
Timeframe: Baseline, assessed every 6 weeks starting from Day1 of Cycle 3 up to end of treatment (Day 1344)
| Intervention | weeks (Median) |
|---|
| Sunitinib + Docetaxel + Trastuzumab | 58.4 |
Overall Survival
(NCT00375999)
Timeframe: One year
| Intervention | month (Median) |
|---|
| Treatment Group | 13.4 |
Objective Response Rate (Complete Response [CR] Plus Partial Response [PR]) Using Response Evaluation Criteria in Solid Tumors (RECIST)
"Complete response is defined as disappearance of all target and nontarget lesions identified and reported at baseline (at or within 4 weeks before the beginning of treatment) by image-based evaluations such as computerized tomography (CT) or magnetic resonance imaging (MRI).~Partial response is defined as persistence of one or more nontarget lesions and at least 30 percent decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameters." (NCT00378573)
Timeframe: 1 year from start of treatment
| Intervention | Participants (Number) |
|---|
| Complete Response | Confirmed Partial Response | Unconfirmed Partial Response | Stable Disease | Progressive Disease | Not Evaluable |
|---|
| Docetaxel, Gemcitabine and Bevacizumab | 0 | 6 | 1 | 2 | 7 | 1 |
Best Overall Response Rate (ORR)
"Percentage of partial and complete responses, according to WHO criteria:~Complete Response: Disappearance of all known disease, determined by 2 observations not less than 4 weeks apart.~Partial Response: Decrease by at least 50% of the diameters of all measurable lesions, determined by 2 observations not less than 4 weeks apart." (NCT00382720)
Timeframe: every 8 weeks up to a maximum of 36 months
| Intervention | percentage of participants (Number) |
|---|
| (TE) Taxotere and Eloxatin | 23.1 |
| (TEF) Taxotere, Eloxatin and 5-fluorouracil | 46.6 |
| (TEX) Taxotere, Eloxatin and Xeloda | 25.6 |
Overall Survival (OS)
The number of months measured from the date of randomization to the date of death due to any cause. (NCT00382720)
Timeframe: up to a maximum of 36 months
| Intervention | months (Median) |
|---|
| (TE) Taxotere and Eloxatin | 8.97 |
| (TEF) Taxotere, Eloxatin and 5-fluorouracil | 14.59 |
| (TEX) Taxotere, Eloxatin and Xeloda | 11.30 |
Time to Progression
"The number of months measured from the day of randomization to the first tumor progression according to World Health Organization (WHO) criteria evaluation of cancer response, or death from any cause.~WHO Criteria for Progressive Disease: ≥ 25% increase in the size of at least one bidimensionally or unidimensionally measurable lesion." (NCT00382720)
Timeframe: every 8 weeks up to a maximum of 36 months
| Intervention | Months (Median) |
|---|
| (TE) Taxotere and Eloxatin | 4.50 |
| (TEF) Taxotere, Eloxatin and 5-fluorouracil | 7.66 |
| (TEX) Taxotere, Eloxatin and Xeloda | 5.55 |
Patients With Measurable Disease the Confirmed Response Rate
(NCT00390416)
Timeframe: up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Confirmed Response Rate | Response Rate (proximal/GEJ tumors) |
|---|
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | 67 | 85 |
1-year Survival
(NCT00390416)
Timeframe: 1 year
| Intervention | months (Median) |
|---|
| Progression Free Survival | Overall Survival |
|---|
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | 12 | 16.8 |
6 Month Progression Free Survival
as measured from the start of the treatment to the date of either documentation of disease progression or death. As we have previously, we will define progression of disease as per RECIST criteria. As per RECIST criteria, any evidence of progression in non-measurable lesions, measurable lesions, or the development of new lesions, would qualify as disease progression .RECIST criteria as defined by CTEP (http://ctep.info.nih.gov/Policies). (NCT00390416)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel, Cisplatin, Fluorouracil, Bevacizumab, Leucovorin | 79 |
Comparison of Toxicity of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])
(NCT00390429)
Timeframe: up to 36 months
| Intervention | participants (Number) |
|---|
| Neutropenia | Febrile neutropenia | Hemoglobin | Diarrhea | Fatigue | Infection (without neutropenia) | Mucositis | Nausea | Rash |
|---|
| Phase I, Group A (Completed) | 10 | 3 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
,| Phase I, Group B (Completed) | 16 | 4 | 1 | 3 | 1 | 3 | 1 | 0 | 1 |
Safety and Toxicity of Erlotinib Hydrochloride and Docetaxel as Measured by NCI CTC v3.0 on Day 8 of Course 1 and on Day 1 of Every Subsequent Course (Phase I [Completed as of 12/01/2004])
(NCT00390429)
Timeframe: Up to 36 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase I, Arm A (Completed) | 17 |
| Phase I, Arm B (Completed) | 25 |
| Phase II | 39 |
Response Rate (Phase II)
Per Response Evaluation Criteria In Solid Tumors Criteria 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. (NCT00390429)
Timeframe: Up to 36 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase II | 11 |
Progression-free Survival (Phase II)
(NCT00390429)
Timeframe: Completion of study (up to 65 months)
| Intervention | months (Median) |
|---|
| Phase II | 4.1 |
Overall Survival (Phase II)
(NCT00390429)
Timeframe: Up to 65 months
| Intervention | months (Median) |
|---|
| Phase II | 18.2 |
Maximum Tolerated Dose of Two Different Schedules of Erlotinib Hydrochloride and Docetaxel (Phase I [Completed as of 12/01/2004])
Maximum tolerated dose (MTD) defined as the highest dose level at which no more than one patient experienced DLT when at least 6 patients were treated at that dose level and were assessable for toxicity, graded according to NCI CTCAE 2.0. (NCT00390429)
Timeframe: up to 36 months
| Intervention | mg (Number) |
|---|
| Phase I, Group A (Completed) | 600 |
| Phase I, Group B (Completed) | 200 |
Frequency and Severity of Toxicities (Phase II)
Treatment-related adverse events Grade ≥3 by NCI CTCAE 2.0. (NCT00390429)
Timeframe: Completion of study (up to 36 months)
| Intervention | participants (Number) |
|---|
| Neutropenia | Febrile neutropenia | Platelets | Diarrhea | Dehydration | Fatigue | Hypokalemia | Hyponatremia | Infection (without neutropenia) | Myalgias | Nausea | Ocular | Pain | Stomatitis |
|---|
| Phase II | 14 | 4 | 1 | 7 | 2 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Overall Survival (OS)
OS was defined as the time from randomization to the date of death, regardless of the cause of death. OS was estimated using Kaplan-Meier methods. (NCT00391092)
Timeframe: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
| Intervention | months (Median) |
|---|
| Trastuzumab + Docetaxel | 38.3 |
| Trastuzumab + Bevacizumab + Docetaxel | 38.5 |
Functional Assessment of Cancer Therapy - Generic (FACT-G) and Functional Assessment of Cancer Therapy - Breast (FACT-B) Subscale Scores
FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate quality of life (QoL) in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general Health-Related QoL (HRQoL): Physical Well-being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB) and Functional Well-Being (FWB); each ranged from 0 (not at all) to 4 (very much). FACT-G ranged between 0-108. Since questions could be reversed coded, as appropriate, before calculating FACT-G, 0 and 108 could be considered worst and best health states. FACT -B is used for assessment of HRQoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: 7 items for each physical, functional, social/family; all 3 ranged from 0-28, emotional (6 items) ranged from 0-24, and breast cancer subscale (9 items) ranged from 0-36. All single-item measures ranges from 0-144. High scale score represents a better QoL. (NCT00391092)
Timeframe: Baseline, Cycles 3, 5, 11, and post progressive disease (PD; 14 to 28 days after disease progression [up to the clinical cutoff of 30 June 2011, up to 4.75 years])
| Intervention | units on a scale (Mean) |
|---|
| Physical Well-Being: Baseline (n=173,189) | Social Well-Being: Baseline (n=173,189) | Emotional Well-Being: Baseline (n=173,189) | Functional Well-Being: Baseline (n=173,189) | Total FACT-G Score: Baseline (n=173,189) | Breast Specific: Baseline (n=173,189) | Total FACT-B Score: Baseline (n=173,189) | Trial Outcome Index: Baseline (n=173,189) | Physical Well-Being: Cycle 3 (n=145,173) | Social Well-Being: Cycle 3 (n=145,173) | Emotional Well-Being: Cycle 3 (n=145,173) | Functional Well-Being: Cycle 3 (n=145, 173) | Total FACT-G Score: Cycle 3 (n=145,173) | Breast Specific: Cycle 3 (n=145,173) | Total FACT-B Score: Cycle 3 (n=145,173) | Trial Outcome Index: Cycle 3 (n=145,173) | Physical Well-Being: Cycle 5 (n=139, 166) | Social Well-Being: Cycle 5 (n=139, 166) | Emotional Well-Being: Cycle 5 (n=139, 166) | Functional Well-Being: Cycle 5 (n=139, 166) | Total FACT-G Score: Cycle 5 (n=139, 166) | Breast Specific: Cycle 5 (n=139, 166) | Total FACT-B Score: Cycle 5 (n=139, 166) | Trial Outcome Index: Cycle 5 (n=139, 166) | Physical Well-Being: Cycle 11 (n=100, 133) | Social Well-Being: Cycle 11 (n=100, 133) | Emotional Well-Being: Cycle 11 (n=100, 133) | Functional Well-Being: Cycle 11 (n=100, 133) | Total FACT-G Score: Cycle 11 (n=100, 133) | Breast Specific: Cycle 11 (n=100, 133) | Total FACT-B Score: Cycle 11 (n=100, 133) | Trial Outcome Index: Cycle 11 (n=100, 133) | Physical Well-Being: Post PD (n=33, 39) | Social Well-Being: Post PD (n=33, 39) | Emotional Well-Being: Post PD (n=33, 39) | Functional Well-Being: Post PD (n=33, 39) | Total FACT-G Score: Post PD (n=33, 39) | Breast Specific: Post PD (n=33, 39) | Total FACT-B Score: Post PD (n=33, 39) | Trial Outcome Index: Post PD (n=33, 39) |
|---|
| Trastuzumab + Bevacizumab + Docetaxel | 21.47 | 20.88 | 15.54 | 16.36 | 74.49 | 22.84 | 97.46 | 60.85 | 19.96 | 21.19 | 16.70 | 16.20 | 74.05 | 23.17 | 97.23 | 59.33 | 19.67 | 20.68 | 17.07 | 15.78 | 73.21 | 23.15 | 96.36 | 58.59 | 21.56 | 20.78 | 17.46 | 16.98 | 76.55 | 23.80 | 100.43 | 62.34 | 20.35 | 19.68 | 14.77 | 15.08 | 70.04 | 22.87 | 92.92 | 58.47 |
,| Trastuzumab + Docetaxel | 21.20 | 20.59 | 14.95 | 16.34 | 73.30 | 21.67 | 94.97 | 59.54 | 20.19 | 20.64 | 16.47 | 15.43 | 72.94 | 22.29 | 95.26 | 58.04 | 19.51 | 19.36 | 16.05 | 14.81 | 69.78 | 21.65 | 91.43 | 55.99 | 21.71 | 19.71 | 15.96 | 16.25 | 73.26 | 21.29 | 94.57 | 59.19 | 19.94 | 19.02 | 14.76 | 14.13 | 67.84 | 22.90 | 90.74 | 56.97 |
Change From Baseline for FACT-G and FACT-B
FACT-G is core questionnaire of Functional Assessment of Chronic Illness Therapy (FACIT) measurement system to evaluate quality of life (QoL) in cancer population. FACT-G consisted of 27 questions grouped in 4 domains of general Health-Related QoL (HRQoL): Physical Well-being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB) and Functional Well-Being (FWB); each ranged from 0 (not at all) to 4 (very much). FACT-G ranged between 0-108. Since questions could be reversed coded, as appropriate, before calculating FACT-G, 0 and 108 could be considered worst and best health states. FACT -B is used for assessment of HRQoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: 7 items for each physical, functional, social/family; all 3 ranged from 0-28, emotional (6 items) ranged from 0-24, and breast cancer subscale (9 items) ranged from 0-36. All single-item measures ranges from 0-144. High scale score represents a better QoL. (NCT00391092)
Timeframe: Baseline, Cycles 3, 5, 11, and post PD (14 to 28 days after disease progression [up to the clinical cutoff of 30 June 2011, up to 4.75 years])
| Intervention | units on a scale (Mean) |
|---|
| Physical Well-Being: Cycle 3 (n=145,173) | Social Well-Being: Cycle 3 (n=145,173) | Emotional Well-Being: Cycle 3 (n=145,173) | Functional Well-Being: Cycle 3 (n=145, 173) | Total FACT-G Score: Cycle 3 (n=145,173) | Breast Specific: Cycle 3 (n=145,173) | Total FACT-B Score: Cycle 3 (n=145,173) | Trial Outcome Index: Cycle 3 (n=145,173) | Physical Well-Being: Cycle 5 (n=139, 166) | Social Well-Being: Cycle 5 (n=139, 166) | Emotional Well-Being: Cycle 5 (n=139, 166) | Functional Well-Being: Cycle 5 (n=139, 166) | Total FACT-G Score: Cycle 5 (n=139, 166) | Breast Specific: Cycle 5 (n=139, 166) | Total FACT-B Score: Cycle 5 (n=139, 166) | Trial Outcome Index: Cycle 5 (n=139, 166) | Physical Well-Being: Cycle 11 (n=100, 133) | Social Well-Being: Cycle 11 (n=100, 133) | Emotional Well-Being: Cycle 11 (n=100, 133) | Functional Well-Being: Cycle 11 (n=100, 133) | Total FACT-G Score: Cycle 11 (n=100, 133) | Breast Specific: Cycle 11 (n=100, 133) | Total FACT-B Score: Cycle 11 (n=100, 133) | Trial Outcome Index: Cycle 11 (n=100, 133) | Physical Well-Being: Post PD (n=33, 39) | Social Well-Being: Post PD (n=33, 39) | Emotional Well-Being: Post PD (n=33, 39) | Functional Well-Being: Post PD (n=33, 39) | Total FACT-G Score: Post PD (n=33, 39) | Breast Specific: Post PD (n=33, 39) | Total FACT-B Score: Post PD (n=33, 39) | Trial Outcome Index: Post PD (n=33, 39) |
|---|
| Trastuzumab + Bevacizumab + Docetaxel | -1.51 | 0.32 | 1.16 | -0.16 | -0.44 | 0.34 | -0.24 | -1.52 | -1.80 | -0.20 | 1.53 | -0.58 | -1.28 | 0.31 | -1.10 | -2.26 | 0.09 | -0.10 | 1.92 | 0.62 | 2.06 | 0.96 | 2.97 | 1.49 | -1.12 | -1.19 | -0.78 | -1.28 | -4.44 | 0.03 | -4.55 | -2.38 |
,| Trastuzumab + Docetaxel | -1.01 | 0.05 | 1.52 | -0.91 | -0.36 | 0.61 | 0.29 | -1.50 | -1.69 | -1.23 | 1.09 | -1.53 | -3.53 | -0.03 | -3.55 | -3.55 | 0.51 | -0.89 | 1.00 | -0.09 | -0.05 | -0.38 | -0.41 | -0.35 | -1.25 | -1.58 | -0.20 | -2.22 | -5.46 | 1.22 | -4.23 | -2.57 |
Time to Treatment Failure (TTF)
TTF was defined as the time between randomization and date of disease progression (per RECIST v1.0; unequivocal progression of existing non-target lesions), death, or withdrawal of treatment due to adverse events, withdrawal of informed consent, insufficient therapeutic response, refusal of treatment/failure to co-operate, or failure to return, whichever occurred first. Progressive disease is defined using 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 recorded since the treatment started. (NCT00391092)
Timeframe: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
| Intervention | months (Median) |
|---|
| Trastuzumab + Docetaxel | 7.7 |
| Trastuzumab + Bevacizumab + Docetaxel | 9.8 |
Progression Free Survival (PFS)
PFS was defined as the time from randomization to time of first documented disease progression (unequivocal progression of existing non-target lesions) or death, whichever occurred first as assessed by Response Evaluation Criteria in Solid Tumors version 1.0 (RECIST v1.0). Progressive disease is defined using 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 recorded since the treatment started. Primary PFS variable was defined based on the investigators' assessments and the statistical conclusions on the primary efficacy endpoint were based on investigator assessed PFS. PFS was estimated using Kaplan-Meier methods. (NCT00391092)
Timeframe: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
| Intervention | months (Median) |
|---|
| Trastuzumab + Docetaxel | 13.7 |
| Trastuzumab + Bevacizumab + Docetaxel | 16.5 |
Percentage of Participants With a Best Overall Response (OR) of Confirmed Complete Response (CR) or Partial Response (PR) in Participants With Measurable Disease at Baseline
Best OR was assessed using RECIST v1.0 criteria. Participants were classified as responders if their best OR was either confirmed CR (disappearance of all target lesions) or confirmed PR (at least a 30% decrease in the sum of the longest diameter [LD] of target lesions, taking as reference the baseline sum LD). Participants without any post-baseline assessments were regarded as non-responders. The 95% CI for the one sample binomial using Pearson-Clopper method. (NCT00391092)
Timeframe: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Docetaxel | 69.9 |
| Trastuzumab + Bevacizumab + Docetaxel | 74.3 |
Duration of Response (DR)
DR was defined as the time when response (CR or PR per RECIST v1.0) was first documented to the date of disease progression per RECIST v1.0 (unequivocal progression of existing non-target lesions) or death. Progressive disease is defined using 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 recorded since the treatment started. (NCT00391092)
Timeframe: Every 9 weeks up to Week 36, thereafter every 12 weeks until disease progression (up to the clinical cutoff of 30 June 2011, up to 4.75 years)
| Intervention | months (Median) |
|---|
| Trastuzumab + Docetaxel | 11.4 |
| Trastuzumab + Bevacizumab + Docetaxel | 14.6 |
Number of Patients With Disease Progression
Number of patients who have died or have had progression of disease. This outcome substitutes for the outcome on Duration of Response. (NCT00391274)
Timeframe: time of response to progressive disease (up to 12 months)
| Intervention | participants (Number) |
|---|
| Pemetrexed | 4 |
| Docetaxel | 1 |
Overall Tumor Response
"Response based on Response Evaluation Criteria In Solid Tumors (RECIST), which define when cancer patients improve (respond), stay the same (stabilize), or worsen (progression) during treatments. 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; SD (stable disease) = small changes that do not meet above criteria." (NCT00391274)
Timeframe: baseline to measured tumor response (up to 24 months after study enrollment)
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Early Death from Malignant Disease | Early Death from Other Causes | Unknown |
|---|
| Docetaxel | 0 | 4 | 46 | 36 | 6 | 1 | 5 |
,| Pemetrexed | 0 | 10 | 33 | 49 | 7 | 1 | 4 |
Overall Survival
Overall survival was defined as the time from the date of study enrollment to the date of death due to any cause. Survival time was censored at the date of last contact for patients who were still alive or lost to follow-up. An amendment allowed for the collection of overall survival on an additional 43 survival events. At the time the original record was released, it was not possible to provide results with the 95% Confidence Interval (CI) since the upper limit was not calculable. The median and 95% CIs are now reported. (NCT00391274)
Timeframe: baseline to date of death from any cause (up to 24 months after study enrollment); amendment (up to 30 months after study enrollment)
| Intervention | months (Median) |
|---|
| Overall Survival (up to 24 months) | Overall Survival (up to 30 months) |
|---|
| Docetaxel | 12.2 | 11.5 |
,| Pemetrexed | 11.7 | 11.4 |
Progression-Free Survival (PFS)
Progression-free survival (PFS) time was defined as the time from the date of study enrollment to the date of the first of the following events: objective disease progression or death due to any cause. For patients who were alive and had not progressed, PFS was censored at the last contact. (NCT00391274)
Timeframe: baseline to measured progressive disease (up to 24 months after study enrollment)
| Intervention | months (Median) |
|---|
| Pemetrexed | 2.8 |
| Docetaxel | 3.1 |
Pharmacology Toxicity
Maximum common terminology criteria (CTC) Grade 3 or 4 toxicities possibly related to study drug are reported. The worst grade event per cycle is reported. Grades range from 0 (none) to 5 (death). Grade 3 events are severe and Grade 4 events are life-threatening. (NCT00391274)
Timeframe: first dose of study drug up to 24 months
| Intervention | participants (Number) |
|---|
| Serum Glutamic Pyruvic Transaminase | Hemoglobin | Leukocytes | Lymphopenia | Neutrophils/Granulocytes | Platelets | Hypokalemia | Anorexia | Constipation | Diarrhea | Enteritis | Fatigue (Asthenia, Lethargy, Malaise) | Febrile Neutropenia | Infection (Clinical/Microbiological: Neutrophils) | Infection (Unknown: Pneumonia) | Mucositis/Stomatitis | Neuropathy: Motor | Pain: Thorax Not Otherwise Specified (NOS) | Pericardial Effusion (Non-Malignant) | Pulmonary/Upper Respiratory - Other | Rash/Desquamation |
|---|
| Docetaxel | 0 | 3 | 21 | 0 | 29 | 0 | 1 | 0 | 1 | 5 | 1 | 5 | 4 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 0 |
,| Pemetrexed | 1 | 7 | 4 | 1 | 5 | 7 | 0 | 1 | 0 | 0 | 0 | 3 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 1 |
Toxicity Profile
Toxicities are assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 3.0. Toxicities are reported as the number of patients who experienced grade 3 or grade 4 adverse events after receiving at least one dose of on-study treatment. (NCT00391586)
Timeframe: 28 days after last on-study treatment
| Intervention | participants (Number) |
|---|
| Acne | Anorexia | Confusion | Dehydration | Diarrhea | Dyspnea | Fatigue | Nasal hemorrhage | Insomnia | Kidney pain | Lymphocyte count decreased | Muscle weakness | Neutrophil count decreased | Desquamating rash | Syncope | Thrombosis (clotting) |
|---|
| Erlotinib Followed by Chemotherapy | 1 | 1 | 1 | 1 | 2 | 3 | 8 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1 |
Duration of Response (DR)
DR defined as time from first objective documentation of complete or partial response that was subsequently confirmed to first documentation of disease progression or to death due to any cause, whichever occurred first. DR calculated (Months) = (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. (NCT00393939)
Timeframe: Baseline up to Month 33
| Intervention | months (Median) |
|---|
| Independent radiology asssessment (n=151, 116) | Investigator's assessment (n=156, 130) |
|---|
| Docetaxel | 7.2 | 5.8 |
,| Docetaxel + Sunitinib | 7.5 | 6.9 |
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). CR defined as the disappearance of all tumor lesions (target and non-target). PR defined as greater than or equal to 30 percent (≥30%) decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions with a non-progressive disease status of the non-target lesions. (NCT00393939)
Timeframe: Baseline up to Month 33
| Intervention | percentage of participants (Number) |
|---|
| Independent radiology assessment | Investigator's assessment |
|---|
| Docetaxel | 39.1 | 43.8 |
,| Docetaxel + Sunitinib | 51.0 | 52.7 |
Progression-Free Survival (PFS)
PFS defined as time from date of randomization to date of the first documentation of objective tumor progression or death due to any cause, whichever occurred first. PFS calculated as (Months) = (first event date minus randomization date plus 1) divided by 30.4. (NCT00393939)
Timeframe: Baseline up to Month 33
| Intervention | months (Median) |
|---|
| Independent radiology assessment | Investigator's assessment |
|---|
| Docetaxel | 8.3 | 6.9 |
,| Docetaxel + Sunitinib | 8.6 | 8.2 |
Overall Survival (OS)
Time from randomization to date of death due to any cause. OS calculated as (Months) = (death date minus date of first dose of study medication plus 1) divided by 30.4. For participants who were alive, overall survival was censored at last contact. (NCT00393939)
Timeframe: Baseline to date of death from any cause (up to Month 33)
| Intervention | months (Median) |
|---|
| Docetaxel + Sunitinib | 26.0 |
| Docetaxel | 28.9 |
Best Response
Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; 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. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria. (NCT00394433)
Timeframe: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
| Intervention | participants (Number) |
|---|
| Partial Response | Stable Disease | Progressive Disease |
|---|
| Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) | 23 | 7 | 5 |
Progression-Free Survival
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Patients alive and progression-free at last follow-up are censored. Per RECIST 1.0 criteria: progressive disease 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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. (NCT00394433)
Timeframe: Disease was evaluated radiologically at baseline and every 2 cycles on treatment. Treatment continued until disease progression or unacceptable toxicity. Treatment duration was a median of 6 cycles/18 weeks given 3-week cycle length (range 1-26 cycles).
| Intervention | months (Median) |
|---|
| Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) | 8.9 |
Overall Survival
Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods. (NCT00394433)
Timeframe: Patients in the study cohort were followed for a median of 12.2 month (up to 40 months).
| Intervention | months (Median) |
|---|
| Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) | 14.9 |
10-month Progression-Free Survival Rate
10-month progression-free survival rate is the probability of patients remaining alive and progression-free at 10-months from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. (NCT00394433)
Timeframe: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment continued until disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 10 months.
| Intervention | probability (%) (Number) |
|---|
| Docetaxel, Cisplatin, Irinotecan and Bevacizumab (TPCA) | 40.0 |
Number of Patients Who Had Response by RECIST Criteria (Response Evaluation Criteria in Solid Tumors)
Complete remission (complete disappearance of disease), partial remission [more than 30% decrease in tumor measurement by RECIST (Response evaluation criteria in solid tumors)]. (NCT00400205)
Timeframe: every 3 months
| Intervention | participants (Number) |
|---|
| Recipients of Docetaxel, Cisplatin, 5-Fluorouracil | 8 |
Tumor Change by Baseline Acetylated Tubulin Expression Score
"Percent change in TNM stage of tumors after three cycles of study treatment was assessed to see if baseline acetylated tubulin (AT) expression predicts treatment success. Decreasing tumor stage change (a negative number) indicates that the tumor is responding to treatment while an increase means that the severity of the tumor is not decreasing. Immunohistochemistry (IHC) analysis of AT expression was performed in formalin-fixed, paraffin-embedded, pre-treatment tissues. The staining was scored based upon intensity according to the following criteria: 0=no staining, 1+=weak tumor staining, 2+=moderate tumor staining, 3+=moderate to high tumor staining, and 4+=high tumor staining.~Data presented are adopted from Saba, NF, et. al. Acetylated Tubulin (AT) as a Prognostic Marker in Squamous Cell Carcinoma of the Head and Neck. Head and Neck Pathology (2014) 8:66-72." (NCT00400205)
Timeframe: Baseline, After 3 cycles of study treatment
| Intervention | percentage of tumor stage change (Mean) |
|---|
| AT score less than or equal to 2 | AT score greater than 2 |
|---|
| Recipients of Docetaxel, Cisplatin, 5-Fluorouracil | -0.8 | -0.36 |
Disease-free Survival (DFS)
Disease-free survival (DFS) is expressed as the percentage of participants who were disease-free and alive at the time of analysis. (NCT00404066)
Timeframe: 42 months (median follow-up)
| Intervention | Participants (Count of Participants) |
|---|
| Neoadjuvant Chemotherapy | 16 |
Percentage of Participants With Pathologic Complete Response (pCR)
Pathologic Complete Response (pCR) rate, assessed as no evidence of invasive disease in excised surgical specimens of breast and/or axilla, in participants who received at least 1 cycle of docetaxel and lapatinib and at least one follow-up evaluation. (NCT00404066)
Timeframe: 12 weeks
| Intervention | percentage of participants (Number) |
|---|
| Neoadjuvant Chemotherapy | 38.9 |
Number of Subjects Showing Partial Response and Stable Disease With the Combination of RAD001 and Docetaxel.
"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 of LD.~Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive disease (PD), taking as reference the smallest sum Longest diameter(LD) since treatment started." (NCT00406276)
Timeframe: 6 weeks
| Intervention | participants (Number) |
|---|
| Partial response | Stable disease | Disease Progression |
|---|
| Docetaxel/RAD001 | 2 | 15 | 7 |
Time to Progression:Time Period (in Months) From Study Entry Until Disease Progression, Death, or Last Date of Contact.
"Period from study entry until disease progression, death, or last date of contact.~Progressive Disease: Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions." (NCT00406276)
Timeframe: 6 months
| Intervention | Months (Median) |
|---|
| Docetaxel/RAD001 | 4.42 |
Toxicities Including Events Other Than Congestive Heart Failure, of Chemotherapy Alone, Bevacizumab With Chemotherapy, and Bevacizumab Alone
The number of patients who experienced Grade 1 or above Adverse Events. Referring to the Adverse Events tables for specifics. (NCT00408408)
Timeframe: 24 months after study entry
| Intervention | participants (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 180 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 157 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 172 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 185 |
| Arm 3A: Docetaxel + Gem Then AC | 158 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 185 |
pCR in the Breast and Nodes
Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen and axillary lymph nodes. (NCT00408408)
Timeframe: Time of surgery, on average 6 or 13 months
| Intervention | percentage of patients (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 27.3 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 24.4 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 18.7 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 27.4 |
| Arm 3A: Docetaxel + Gem Then AC | 22.9 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 30.3 |
Clinical Overall Response: cOR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
The percentage of patients assessed by physical exam as Clinical Complete Response or Clinical Partial Response according to RECIST. (NCT00408408)
Timeframe: Three to four weeks after the last chemotherapy dose on average 6 or 13 months
| Intervention | percentage of patients (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 79.9 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 87.7 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 75.4 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 90.7 |
| Arm 3A: Docetaxel + Gem Then AC | 83.3 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 80.5 |
Clinical Overall Response (cOR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at the Completion of the Docetaxel-based Portion of Chemotherapy
Percentages of patients assessed as Clinical Complete Response or Clinical Partial Response according to RECIST. (NCT00408408)
Timeframe: Assessed at cycle 5 of chemotherapy, on average at 15 weeks
| Intervention | percentage of patients (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 77 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 87.6 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 73.7 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 84 |
| Arm 3A: Docetaxel + Gem Then AC | 82.6 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 88 |
Clinical Complete Response (cCR) Following Docetaxel Alone, Docetaxel/Capecitabine, and Docetaxel/Gemcitabine Hydrochloride, With or Without Bevacizumab, as Assessed by Physical Exam at Completion of Therapy
Percentages of patients assessed as Clinical Complete Response or Clinical Partial Response according to RECIST. (NCT00408408)
Timeframe: Assessed at cycle 5 of chemotherapy, on average at 15 weeks
| Intervention | percentage of patients (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 30 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 43.3 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 29.8 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 34.5 |
| Arm 3A: Docetaxel + Gem Then AC | 37.9 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 42 |
Clinical Complete Resonse: cCR as Assessed by Physical Exam at the Completion of the Sequential Chemotherapy Regimens
The percentage of patients assessed by physical exam as Clinical Complete Response according to RECIST. (NCT00408408)
Timeframe: Three to four weeks after the last chemotherapy dose, on average at 6 or 13 months
| Intervention | percentage of patients (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 52.3 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 64.6 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 51.3 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 59.1 |
| Arm 3A: Docetaxel + Gem Then AC | 52.6 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 60 |
Pathologic Complete Response (pCR) of the Primary Tumor in the Breast
Percentage of patients absent of histologic evidence of invasive tumor cells in the surgical breast specimen. (NCT00408408)
Timeframe: Time of surgery, on average 6 or 13 months
| Intervention | percentage of patients (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 33.7 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 31.6 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 23.5 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 36.1 |
| Arm 3A: Docetaxel + Gem Then AC | 27.6 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 35.8 |
Surgical Complication
Number of patients with Grade 4 or above surgery-related toxicities (NCT00408408)
Timeframe: 24 months after study entry
| Intervention | participants (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 1 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 1 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 0 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 1 |
| Arm 3A: Docetaxel + Gem Then AC | 0 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 1 |
Disease-free Survival (DFS)
Percentage of patients free from local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, contralateral breast cancer, second primary cancer after 5 years. (NCT00408408)
Timeframe: Measured through 5 years after study enrollment
| Intervention | percentage of patients (Number) |
|---|
| Arm 1A: Docetaxel Then AC | 73.4 |
| Arm 1B Docetaxel + Bev Then AC + Bev | 72.2 |
| Arm 2A: Docetaxel + Capecitabine Then AC | 68.5 |
| Arm 2B: Docetaxel + Cape + Bev Then AC + Bev | 77.1 |
| Arm 3A: Docetaxel + Gem Then AC | 72.9 |
| Arm 3B: Docetaxel + Gem + Bev Then AC + Bev | 74.8 |
Number of Participants With Pathological Response
Number of participants who completed neoadjuvant chemotherapy and underwent repeat CT and endoscopic ultrasound (EUS) with pathological complete response (pCR), partial response in the primary tumor, stable disease or progressive disease as defined by EUS criteria. (NCT00414271)
Timeframe: up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| pathological complete response (pCR) | partial response | stable disease | progressive disease |
|---|
| Open Label, Single Arm | 0 | 4 | 8 | 3 |
Feasibility and Safety of Pre-operative Chemotherapy in Locally Advanced Gastric Cancer as Assessed by Number of Participants Who Experienced Adverse Events Grade 3 or Higher as Defined by CTCAE.
Number of participants who experience Grade 3/4 neutropenia, Grade 3 nausea or Grade 3 diarrhea. (NCT00414271)
Timeframe: up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3/4 neutropenia | Grade 3 nausea | Grade 3 diarrhea |
|---|
| Open Label, Single Arm | 10 | 1 | 2 |
Progression-free Survival as Measured by Number of Participants Without Disease Progression.
(NCT00414271)
Timeframe: up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Open Label, Single Arm | 3 |
Overall Survival
Median number of months participants alive at the time of observation. Calculated using Kaplan-Meier method. (NCT00414271)
Timeframe: up to 8 years
| Intervention | months (Median) |
|---|
| Open Label, Single Arm | 17.1 |
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
| Intervention | participants (Number) |
|---|
| Phase I: Dose Level 1 | 0 |
| Phase 1 Dose Level II: | 0 |
| Phase I Dose Level III | 0 |
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. (NCT00425750)
Timeframe: 7.55 months (average duration, on study to off study)
| Intervention | participants (Number) |
|---|
| Partial Response | Progressive Disease | Stable Disease | Not Evaluable |
|---|
| Bortezomib; Docetaxel | 1 | 10 | 10 | 4 |
Progression-free Survival
Median duration of survival without disease progression, calculated as on-study date to date of progression or date of death (censored) or off-study date (censored) (NCT00425750)
Timeframe: 7.55 months (average duration, on study to off study)
| Intervention | Month (Median) |
|---|
| Bortezomib; Docetaxel | 2.27 |
Overall Survival
Median survival time of patients, calculated as on-study date to date of death or off-study date (censored) (NCT00425750)
Timeframe: 7.55 months (average duration, on study to off study)
| Intervention | Month (Median) |
|---|
| Bortezomib; Docetaxel | 5.13 |
Tumor Response Measured by CT Scans After Each Set of 3 Cycles of Chemotherapy
(NCT00426127)
Timeframe: 9 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel and Liposomal Doxorubicin Combined With Enoxaparin | 1 |
Number of Blood Draws With Incidence of Elevated D-Dimer Measured by Drawing D-Dimer Levels Every Cycle
Incidence of elevated D-Dimer was defined as >.50 as drawn every cycle. Incidence of elevated D-Dimer was tested to determine safety and efficacy of the treatment regimen on patients with advanced pancreatic cancer. (NCT00426127)
Timeframe: 3 weeks
| Intervention | Blood draw (Number) |
|---|
| Incidences within normal range D-Dimer <.50 | Incidence with elevated D-Dimer >.50 |
|---|
| Docetaxel and Liposomal Doxorubicin Combined With Enoxaparin | 3 | 1 |
Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen.
The trial was designed as a single-stage phase II rather then usual two-stage design because of the progression free survival (PFS) primary endpoint, as it is impractical to wait to assess PFS for patients in the first stage. We will consider a PFS of 50% at twelve months (median PFS of 12 months) or less uninteresting and a PFS of 70% at twelve months (median PFS of twenty months) worthy of pursuing the regimen in a future trials. The single-stage design is as follows: p0=0.50, p1=0.70, α=0.10, β= 0.10. This leads to a total sample size of 39 patients, 24 or higher of who are progression-free at 12 months. (NCT00428922)
Timeframe: up to 3 years
| Intervention | months (Median) |
|---|
| Trastuzumab, Bevacizumab, and Docetaxel | 14.3 |
Overall Clinical Benefit Rate (CR+PR+SD)
Defined as best response of CR or PR or stable disease for at least 24 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/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 Progression of Disease (POD); POD, 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; Complete Response (CR), Disappearance of all target lesions (NCT00428922)
Timeframe: at least 24 weeks
| Intervention | percent of patients (Number) |
|---|
| Trastuzumab, Bevacizumab, and Docetaxel | 69 |
Changes in CTCs as Predictors of PFS and Clinical Benefit
Circulating tumor cells (CTCs) evaluated at baseline (day 1 of treatment) and after 1 treatment cycle (day 22 prior to cycle 2 treatment). (NCT00428922)
Timeframe: Day 1 and Day 22
| Intervention | patients with detected CTCs (Number) |
|---|
| Trastuzumab, Bevacizumab, and Docetaxel | 7 |
5-year bPFS Rate
Proportion of participants surviving 5 years from randomization without biochemical progression or death. (NCT00430183)
Timeframe: 5 years
| Intervention | Proportion of participants (Number) |
|---|
| Arm A: Docetaxel + LHRH Agonist + Surgical Intervention | 0.81 |
| Arm B: Surgical Intervention | 0.74 |
Proportion of Biochemical Progression-Free Survival (bPFS Proportion) at 3 Years
Proportion of participants surviving 3 years from randomization without biochemical progression or death. bPFS was defined as the time from randomization to the date of the first documented biochemical progression or death. Progression will be defined as having experienced either of the following: a serum PSA level > 0.2 ng/mL that increases on 2 consecutive occasions each of which is at least 3 months apart or death occurs. The time of biochemical failure is measured from the date of randomization to the date of the first PSA level > 0.2 ng/mL. (NCT00430183)
Timeframe: Up to 3 years
| Intervention | proportion of patients (Number) |
|---|
| Arm A: Docetaxel + LHRH Agonist + Surgical Intervention | 0.89 |
| Arm B: Surgical Intervention | 0.84 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Group 1 (Luminal A) Standard Treatment | 31 |
| Group 1 (Luminal A) Selective Treatment | 23 |
| Group 2 (Basal) Standard Treatment | 32 |
| Group 2 (Basal) Selective Treatment | 36 |
Overall Objective Response Rate According to RECIST (Phase II)
The percentage of participants in the Phase II arm with an objective response defined as a measurable response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. Standard RECIST criteria were followed to evaluate response and progression. All documented responses were required to undergo confirmation by imaging, examination, or both, no sooner than 4 weeks after the initial documentation of response. In the absence of new symptoms, this response assessment was consistently done after two additional cycles of therapy. (NCT00436501)
Timeframe: Up to 6 months
| Intervention | percentage of participants (Number) |
|---|
| Phase II: VEGF Trap, Docetaxel | 54 |
Maximum Tolerated Dose of VEGF Trap (Phase I)
Escalating dose levels of VEGF Trap were administered intravenously over three dose levels (2, 4, or 6 mg/kg; one dose every 21 days) to identify the maximum tolerated dose (MTD). The MTD is defined as the highest dose level below which 2 or more patients encounter a dose limiting toxicity (DLT), graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. MTD established on absence of observed DLT(s) in either cycle 0 (single agent) or cycle 1 (combination therapy) of any given dose level. (NCT00436501)
Timeframe: 21 day cycle, up to 3 cycles
| Intervention | mg/kg (Number) |
|---|
| Phase I VEGF Trap, Docetaxel | 6 |
Number of Participants With Clinical Response (Partial Response or Complete Response) According to the Response Evaluation Criteria in Solid Tumors (RECIST)
Frequency of clinical response (partial response or complete response) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance all target lesions; Partial Response (PR): >/= 30% decrease in sum of longest diameter (LD) of target lesions, reference baseline sum LD; Progressive Disease (PD): >/= 20% increase in sum of LD of target lesions, reference smallest sum LD recorded since treatment started or appearance of 1+ new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference smallest sum LD since treatment started. (NCT00436501)
Timeframe: Up to 6 months
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response |
|---|
| Phase I VEGF Trap, Docetaxel | 0 | 2 |
,| Phase II: VEGF Trap, Docetaxel | 11 | 14 |
Number of Participants Meeting the Criteria for On-study Abnormal Results Grade 3-4 of Clinical Laboratory Tests
ULN=upper limit of normal. Graded by Common Toxicity Criteria: 1 (least severe) to 4 (life threatening ). Absolute neutrophil count (*10^9/L), Grade 3, <1.0-0.5; Grade 4, <0.5. Hemoglobin (mmol/L), Grade 3, <4.9-4.0; Grade 4, <4.0. Platelets (*10^9/L), Grade 3, <50.0-25.0; Grade 4, <25.0. Leukocytes (*10^9/L) Grade 3, <2.0-1.0; Grade 4, <1.0. ALP, ALT, and AST (*ULN), Grade 3, >5.0-20.0; Grade 4, >20.0. Total bilirubin (*ULN), Grade 3, >3.0-10.0; Grade 4, >10.0. Creatinine (*ULN), Grade 3, >3.0-6.0; Grade 4, >6.0. Hypercalcemia (mmol/L), Grade 3, >3.1-3.4; Grade 4, >3.4. Hypocalcemia mmol/L), Grade 3, <1.75-1.5; Grade 4, <1.5. Hyperkalemia (mmol/L), Grade 3, >6.0-7.0; Grade 4, >7.0. Hypokalemia (mmol/L), Grade 3, <3.0-2.5; Grade 4, <2.5. Hypernatremia (mmol/L), Grade 3, >155-160; Grade 4, >160. Hyponatremia (mmol/L), Grade 3, <130-120; Grade 4, <120. Phosphorus (mmol/L), Grade 3, <0.6-0.3; Grade 4, <0.3. Prothrombin time (seconds), Grade 3, >2.0; Grade 4, not defined. (NCT00439270)
Timeframe: From Day 2 of Cycle 1 to up to 30 days after last dose of study drug (up to approximately 49 months)
| Intervention | Participants (Number) |
|---|
| Absolute neutrophil count | Hemoglobin | Platelet count | Leukocytes | Alanine aminotransferase (ALT) | Aspartate aminotransferase (AST) | Alkaline phosphatase (ALP) | Total bilirubin | Hypercalcemia | Hypocalcemia | Creatinine | Hyperkalemia | Hypokalemia | Hypernatremia | Hyponatremia | Phosphorus, inorganic | Prothrombin time |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 1 | 0 |
,| Dasatinib, 120 mg + Docetaxel, 75 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
,| Dasatinib, 50 mg + Docetaxel, 60 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Dasatinib, 50 mg + Docetaxel, 75 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
,| Dasatinib, 70 mg + Docetaxel, 75 mg/m^2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants by Best On-study Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
"RECIST for target lesions: Complete Response (CR)=disappearance of clinical and radiologic evidence of target lesions. Partial Response (PR)=a 30% or greater decrease in the sum of the longest diameter (LD) of all lesions in reference to the baseline sum LD. Stable disease (SD)=neither sufficient increase to qualify for Progressive Disease (PD) nor sufficient shrinkage to qualify for PR.~PD=a 20% or greater increase in the sum of LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline; unequivocal progression of nonmeasurable disease/lesions as evaluated by CT scan or MRI (not as evaluated by radionuclide bone scan) and/or new lesions are present.~To qualify as SD, patients had to exhibit SD for a minimum of 18 weeks. Those with evaluations noted as SD prior to 18 weeks and discontinued were reported as no change." (NCT00439270)
Timeframe: Pretreatment visit then every 6 weeks thereafter (up to 51.6 months)
| Intervention | Participants (Number) |
|---|
| Complete response | Partial response | Stable disease | No change | Progressive disease | Not evaluable |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 0 | 15 | 1 | 3 | 2 | 13 |
Number of Participants by Best On-study Bone Scan Assessment From Baseline
Stable=no new lesions appeared at any 6-week assessment or new pain was not developed in an area that was previously visualized for a minimum of 18 weeks; no change=stable disease prior to 18 weeks and then discontinued treatment; progression=2 or more new areas of focal uptake or new adverse clinical symptoms in an area previously visualized; improved=disappearance of at least 1 lesion, no new lesions appearing since the most recent prior assessment, and new pain not developing in an area that was previously visualized. (NCT00439270)
Timeframe: From Day 1 of therapy to last bone scan assessment (up to 51.6 months)
| Intervention | Participants (Number) |
|---|
| Improved | Stable | No change | Progression | Not evaluable |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 8 | 17 | 7 | 1 | 1 |
Maximum Observed Plasma Concentration (Cmax) of Dasatinib and of Docetaxel
(NCT00439270)
Timeframe: Docetaxel: Cycle 1, Day 1 at 0, 0.5, 1, 1.25, 1.5, 2, 3, 4, 7, 10, 24, and 48 hours postdose; dasatanib: Cycle 1, Day 14 at 0, .5, 1, 2, 3, 4, 7, 10, and 24 hours postdose
| Intervention | ng/mL (Geometric Mean) |
|---|
| Dasatinib (n=3, 1, 3, 29, 3) | Docetaxel (n=3, 3, 3, 34, 3) |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 83.91 | 2125.49 |
,| Dasatinib, 120 mg + Docetaxel, 75 mg/m^2 | 164.99 | 2412.41 |
,| Dasatinib, 50 mg + Docetaxel, 60 mg/m^2 | 42.70 | 2226.25 |
,| Dasatinib, 50 mg + Docetaxel, 75 mg/m^2 | 21.99 | 1763.34 |
,| Dasatinib, 70 mg + Docetaxel, 75 mg/m^2 | 30.00 | 1748.43 |
Area Under the Concentration-time Curve (AUC) From 0 to 10 Hours Postdose (AUC [0-10])and AUC in 1 Dosing Interval, From Time 0 to 24 Hours (AUC[Tau])of Dasatinib Coadministered With Docetaxel
(NCT00439270)
Timeframe: Cycle 1, Day 14 at 0, 0.5 , 1, 2, 3, 4, 7, 10, and 24 hours postdose
| Intervention | ng.h/mL (Geometric Mean) |
|---|
| AUC(0-10) (n=3, 1, 3, 28, 3) | AUC(tau) (n=3, 1, 3, 21, 3) |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 277.07 | 389.66 |
,| Dasatinib, 120 mg + Docetaxel, 75 mg/m^2 | 461.82 | 556.47 |
,| Dasatinib, 50 mg + Docetaxel, 60 mg/m^2 | 173.13 | 205.43 |
,| Dasatinib, 50 mg + Docetaxel, 75 mg/m^2 | 71.75 | 82.20 |
,| Dasatinib, 70 mg + Docetaxel, 75 mg/m^2 | 149.79 | 200.63 |
Recommended Phase 2 Dose of Dasatinib Administered With Docetaxel, 75 mg/m^2
Because no dose-limiting toxicities occurred, the recommended dose of dasatinib used in Phase 2 was based on findings from ongoing studies in chronic myelogenous leukemia and experience from the previous Phase 2 study of single-agent dasatinib in chronic refractory prostate cancer. The recommended Phase 2 dose of docetaxel (75 mg/m^2) was based on the docetaxel package insert. (NCT00439270)
Timeframe: From Day 3 of first 21-day cycle to Cycle 2 , Day 21 (or Study Day 42)
| Intervention | mg (Number) |
|---|
| All Treated (Phase 1) | 100 |
Percentage of Participants With Improvement on Bone Scan
Improvement=disappearance of at least 1 lesion, no new lesions appearing since the most recent prior assessment, and new pain not developing in an area that was previously visualized (NCT00439270)
Timeframe: From Day 1 of therapy to last bone scan assessment (up to 51.6 months)
| Intervention | Percentage of participants (Number) |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 23.5 |
Percentage of Participants With an Objective Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST)
Objective response rate is defined as the percentage of participants who have achieved best responses of confirmed Complete Response (CR) or Partial Response (PR) where confirmed requires repeat evaluations for a minimum of 4 weeks after the criteria for response are first met. RECIST: CR=disappearance of clinical and radiologic evidence of target lesions; PR=a 30% or greater decrease in the sum of the longest diameter (LD) of all lesions in reference to the baseline sum LD. (NCT00439270)
Timeframe: Pretreatment visit then every 6 weeks thereafter (up to 51.6 months)
| Intervention | Percentage of participants (Number) |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 44.1 |
Percentage of Participants With a Prostate Specific Antigen (PSA) Response
PSA response rate is defined as a decrease of >=50% in PSA levels from baseline, sustained for at least 6 weeks and confirmed by at least 2 measurements (NCT00439270)
Timeframe: At pretreatment visit, and on Day 1 of Cycles 2 through 12, then every other cycle, where investigator deems appropriate, and at end of treatment (up to 51.6 months)
| Intervention | Percentage of participants (Number) |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 64.7 |
Number of Months of Progression-free Survival (PFS)
"PFS defined as time in months from the first dosing date to the date of disease progression or the date of death. Patients who neither progressed nor died were censored on the date of their last on-study prostate specific antigen (PSA) measurement, tumor assessment, or radionuclide bone scan assessment (whichever occurred last). Disease progression defined as either of the following: progression on radionuclide bone scan, death, or at least 2 of the following:~tumor progression, as defined by modified Response Evaluation Criteria in Solid Tumors; PSA progression; or investigator-defined clinical progression based on physical examination, history, symptoms, and performance status." (NCT00439270)
Timeframe: Patients with an event: time from first dose to disease progression or death, whichever occurs first. Patients without an event: time to last on-study PSA measurement, tumor assessment, or radionuclide bone scan assessment, whichever occurs last
| Intervention | Months (Median) |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 11.5 |
Maximum Tolerated Dose (MTD) of Dasatinib Administered With Docetaxel
MTD was defined by dose-limiting toxicity (DLT) criteria. DLT was defined as grade 4 neutropenia causing treatment interruption for >14 days, febrile neutropenia, grade 4 thrombocytopenia, grade 3 thrombocytopenia with a bleeding episode requiring platelet transfusion, nausea and/or vomiting despite medical intervention/prophylaxis causing treatment interruption for >14 days, grade 3-4 asthenia/fatigue, any other grade >=3 nonhematologic toxicity except alopecia or transient arthralgia/myalgia (unless unresponsive to intervention), or interruption of study drug for >14 days due to toxicity. When defined, the MTD would serve as recommended Phase 2 dose of each drug in the combination of oral dasatinib and intravenous docetaxel. (NCT00439270)
Timeframe: From Day 3 of first 21-day cycle to Cycle 2 , Day 21 (or Study Day 42)
| Intervention | mg (Number) |
|---|
| All Treated (Phase 1) | NA |
Duration of Prostate Specific Antigen (PSA) Response
Duration of response is computed for participants with confirmed PSA response. It is measured in months from the time of the first of 2 consecutive measurements meeting the criteria for confirmed PSA response to the date of the first of 3 consecutive measurements that confirm PSA progression, the date of disease progression, or the date of death. Participants who neither progressed (PSA or disease) nor died were censored on the date of their last PSA assessment. PSA response is defined as a decrease of >=50% in PSA levels from baseline, sustained for at least 6 weeks and confirmed by at least 2 measurements. PSA progression is defined as 3 consecutive increases in PSA from baseline or nadir, each measurement at least 1 week apart. The final confirming PSA measurement had to be ≥5ng/mL higher than baseline or nadir and also represent at least a 50% increase from baseline or nadir (ie, the value is ≥1.5*baseline or nadir PSA). (NCT00439270)
Timeframe: At pretreatment visit, and on Day 1 of Cycles 2 through 12, then every other cycle, where investigator deems appropriate, and at end of treatment
| Intervention | Months (Median) |
|---|
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 9.5 |
Area Under the Concentration-time Curve (AUC) From Time 0 to Infinity (AUC[Inf]) of Docetaxel
(NCT00439270)
Timeframe: Cycle 1, Day 1 at 0, 0.5, 1, 1.25, 1.5, 2, 3, 4, 7, 10, 24, and 48 hours postdose
| Intervention | ng.h/mL (Geometric Mean) |
|---|
| Dasatinib, 50 mg + Docetaxel, 60 mg/m^2 | 3085.59 |
| Dasatinib, 50 mg + Docetaxel, 75 mg/m^2 | 2064.49 |
| Dasatinib, 70 mg + Docetaxel, 75 mg/m^2 | 2113.37 |
| Dasatinib, 100 mg + Docetaxel, 75 mg/m^2 | 2663.83 |
| Dasatinib, 120 mg + Docetaxel, 75 mg/m^2 | 3283.27 |
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
| Intervention | Percentage of Participants (Mean) |
|---|
| Stratum 1: TAC + Bevacizumab | 4.3 |
| Stratum 2: TCH + Bevacizumab | 0 |
Number of Participants With DLTs
Dose limiting toxicity (DLTs) was determined during the Wrst two cycles of treat- ment. The definitions of DLTs were as follows: (1) grade 4 neutropenia lasting for more than 5 days, or grade 3/4 neu- tropenia with fever; (2) grade 4 thrombocytopenia; (3) any other grade 3 non-hematological toxicity (excluding alope- cia); or (4) treatment delay of more than 2 weeks following the time of planned treatment. Maximal tolerated dose was defined as that the DLTs were observed in two or more patients from a cohort of two to six patients (NCT00446290)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| DXO Arm | 3 |
Overall Survival
(NCT00448760)
Timeframe: 24 months
| Intervention | months (Median) |
|---|
| Single Arm | 21.4 |
Pathologic Complete Response
No evidence of cellular residual cancerous cells as evidenced by tumor tissue samples taken via surgery at the end of neo-adjuvant chemotherapy. (NCT00448760)
Timeframe: 8 - 16 weeks
| Intervention | percentage of participants (Number) |
|---|
| Single Arm | 16.7 |
Clinical Response
"Overall response = Complete response (CR) + Partial Response (PR). Evaluated via endoscopic ultrasounds, PET and CT scans of the chest:~Complete Response (CR) applies to participants complete disappearance of all measurable and evaluable disease. No new lesion. No disease related symptoms. No evidence of non-evaluable disease, including tumor markers and other laboratory values.~Partial Response (PR) applies to participants with at least 50 percent reduction in the sum of the products of bi-dimensional perpendicular diameters of all measurable lesions. No progression of evaluable disease. No new lesions." (NCT00448760)
Timeframe: 8 - 16 weeks
| Intervention | percentage of participants (Number) |
|---|
| Single Arm | 72.4 |
Progression-Free Survival (PFS)
PFS was defined as the time from the start of treatment to the first documentation of disease progression or death for any cause. Disease progression was based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 criteria and 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 one or more new lesions. (NCT00454636)
Timeframe: Approximately 3.25 years
| Intervention | months (Median) |
|---|
| Cisplatin / Capecitabine | 4.43 |
| Epirubicin / Cisplatin / Capecitabine | 5.17 |
| Epirubicin / Oxaliplatin / Capecitabine | 7.07 |
| Docetaxel / Cisplatin / Capecitabine | 7.87 |
Overall Survival (OS)
OS was defined as the time elapsing from the date of the start of treatment until death, or last known follow-up. (NCT00454636)
Timeframe: Approximately 3.25 years
| Intervention | months (Median) |
|---|
| Cisplatin / Capecitabine | 10.23 |
| Epirubicin / Cisplatin / Capecitabine | 8.87 |
| Epirubicin / Oxaliplatin / Capecitabine | 13.87 |
| Docetaxel / Cisplatin / Capecitabine | 12.43 |
Overall Response Rate (ORR)
ORR was defined as the percentage of participants achieving either a complete response (CR) or a partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 criteria. CR was defined as the disappearance of all target lesions; for non-target lesions, disappearance of lesions and normal tumor marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using the baseline sum LD as reference. (NCT00454636)
Timeframe: Approximately 3.25 years
| Intervention | percentage of participants (Number) |
|---|
| Cisplatin / Capecitabine | 43.3 |
| Epirubicin / Cisplatin / Capecitabine | 40.7 |
| Epirubicin / Oxaliplatin / Capecitabine | 69.6 |
| Docetaxel / Cisplatin / Capecitabine | 59.6 |
Duration of Response
Duration of Response was defined as the time of complete response (CR) or partial response (PR) until the first date of recurrent or progressive disease, based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 criteria. CR was defined as the disappearance of all target lesions; for non-target lesions, disappearance of lesions and normal tumor marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using the baseline sum LD as reference. Progressive disease 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 one or more new lesions. (NCT00454636)
Timeframe: Approximately 3.25 years
| Intervention | days (Mean) |
|---|
| Cisplatin / Capecitabine | 308.92 |
| Epirubicin / Cisplatin / Capecitabine | 154.09 |
| Epirubicin / Oxaliplatin / Capecitabine | 203.06 |
| Docetaxel / Cisplatin / Capecitabine | 205.52 |
Time to Response
Time to Response was defined as the date of start of treatment until the first date of complete response (CR) or a partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.0 criteria. CR was defined as the disappearance of all target lesions; for non-target lesions, disappearance of lesions and normal tumor marker levels. PR was defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, using the baseline sum LD as reference. (NCT00454636)
Timeframe: Approximately 3.25 years
| Intervention | days (Mean) |
|---|
| Cisplatin / Capecitabine | 132.92 |
| Epirubicin / Cisplatin / Capecitabine | 126.64 |
| Epirubicin / Oxaliplatin / Capecitabine | 123.50 |
| Docetaxel / Cisplatin / Capecitabine | 138.16 |
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
| Intervention | hr (Mean) |
|---|
| Axitinib + Paclitaxel (Cohort 4) | 12.51 |
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 8.36 |
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
| Intervention | hr (Mean) |
|---|
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 2.77 |
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
| Intervention | L/hr (Mean) |
|---|
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 7.26 |
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
| Intervention | Liter/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 |
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
| Intervention | Liter/hr (Mean) |
|---|
| Axitinib + Capecitabine (Cohort 6) | 209.05 |
| Axitinib + Capecitabine (Cohort 7) | 314.12 |
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
| Intervention | ng*hr/mL (Mean) |
|---|
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 55580.26 |
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
| Intervention | ng*hr/mL (Mean) |
|---|
| Axitinib + Docetaxel (Cohort 5) | 3478.49 |
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
| Intervention | ng*hr/mL (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 10991.16 |
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
| Intervention | ng*hr/mL (Mean) |
|---|
| Axitinib + Paclitaxel (Cohort 4) | 5683.55 |
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 19959.91 |
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
| Intervention | ng*hr/mL (Mean) |
|---|
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 133032.97 |
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
| Intervention | nanogram*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 |
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
| Intervention | ng*hr/mL (Mean) |
|---|
| Axitinib + Capecitabine (Cohort 6) | 20534.52 |
| Axitinib + Capecitabine (Cohort 7) | 22163.88 |
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
| Intervention | ng*hr/mL (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 2932.43 |
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 2703.92 |
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
| Intervention | ng/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 |
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
| Intervention | ng/mL (Mean) |
|---|
| Axitinib + Capecitabine (Cohort 6) | 10808.00 |
| Axitinib + Capecitabine (Cohort 7) | 10588.38 |
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
| Intervention | ng/mL (Mean) |
|---|
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 23383.33 |
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
| Intervention | ng/mL (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 1680.54 |
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 1176.00 |
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
| Intervention | ng/mL (Mean) |
|---|
| Axitinib + Docetaxel (Cohort 5) | 3130.00 |
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
| Intervention | ng/mL (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 20635.29 |
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
| Intervention | ng/mL (Mean) |
|---|
| Axitinib + Paclitaxel (Cohort 4) | 3698.33 |
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 6105.00 |
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
| Intervention | ng/mL (Mean) |
|---|
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 83925.00 |
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)]
| Intervention | mg 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 |
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
| Intervention | Percentage 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 |
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
| Intervention | L/hr (Mean) |
|---|
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 12.57 |
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
| Intervention | L/hr (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 46.31 |
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 46.80 |
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
| Intervention | L/hr (Mean) |
|---|
| Axitinib + Docetaxel (Cohort 5) | 42.96 |
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
| Intervention | L/hr (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 224.36 |
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
| Intervention | L/hr (Mean) |
|---|
| Axitinib + Paclitaxel (Cohort 4) | 30.48 |
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 21.61 |
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
| Intervention | hr (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 |
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
| Intervention | hr (Mean) |
|---|
| Axitinib + Capecitabine (Cohort 6) | 0.85 |
| Axitinib + Capecitabine (Cohort 7) | 1.44 |
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
| Intervention | hr (Mean) |
|---|
| Axitinib + Paclitaxel + Carboplatin (Combined Cohort 1, 2, 3) | 2.62 |
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
| Intervention | hr (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 2.61 |
| Axitinib + Pemetrexed + Cisplatin (Cohort 9) | 3.91 |
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
| Intervention | hr (Mean) |
|---|
| Axitinib + Docetaxel (Cohort 5) | 11.49 |
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
| Intervention | hr (Mean) |
|---|
| Axitinib + Gemcitabine + Cisplatin (Cohort 8) | 0.29 |
Overall Response Rate (ORR) During the First-line Treatment Phase
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 (SLD) of target lesions from baseline; Overall Response (OR) = CR + PR. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. ORR is the percentage of subjects with an overall response among the analysis population. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 67 months
| Intervention | Percentage of Participants (Mean) |
|---|
| Panitumumab Plus Chemotherapy | 44.23 |
| Chemotherapy Alone | 37.25 |
Duration of Response (DOR) During the First-line Treatment Phase
Calculated only for the subset of subjects who have an overall response of CR or PR while on first-line treatment phase (subsequently confirmed at least 4 weeks thereafter), and is defined as time from the first CR or PR to the first observed disease progression by a modified RECIST v1.0. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 67 months
| Intervention | Months (Median) |
|---|
| Panitumumab Plus Chemotherapy | 8.0 |
| Chemotherapy Alone | 5.1 |
Overall Response Rate (ORR) During the Second-line Treatment Phase
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 (SLD) of target lesions from baseline; Overall Response (OR) = CR + PR. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. ORR is the percentage of subjects with an overall response among the analysis population. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 57 months
| Intervention | Percentage of Participants (Mean) |
|---|
| Chemotherapy Alone | 13.33 |
Time to Response (TTR) During the Second-line Treatment Phase
Time from the first dose of panitumumab monotherapy to the first CR or PR during second-line treatment phase (subsequently confirmed at least 4 weeks thereafter) (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 57 months
| Intervention | Weeks (Mean) |
|---|
| Chemotherapy Alone | 10.6 |
Time to Response (TTR) During the First-line Treatment Phase
Time from the date of randomization to the first CR or PR during first line treatment phase (subsequently confirmed at least 4 weeks thereafter) (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 67 months
| Intervention | Weeks (Mean) |
|---|
| Panitumumab Plus Chemotherapy | 8.8 |
| Chemotherapy Alone | 10.6 |
Rate of Disease Control (RDC) During the Second-line Treatment Phase
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 (SLD) of target lesions from baseline; Disease Progression (PD), >=20% increase in the SLD of target lesions from nadir; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. A best overall response of SD requires a visit response of SD or better no earlier than 35 days after the first dose date in second-line treatment. RCD is the percentage of subjects with a best overall response of CR, PR or SD among the analysis population. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 57 months
| Intervention | Percentage of Participants (Mean) |
|---|
| Chemotherapy Alone | 53.33 |
Rate of Disease Control (RDC) During the First-line Treatment Phase
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 (SLD) of target lesions from baseline; Disease Progression (PD), >=20% increase in the SLD of target lesions from nadir; Stable Disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. An overall response of CR or PR must be confirmed at least 4 weeks after the criteria for response are first met. A best overall response of SD requires a visit response of SD or better no earlier than 35 days after randomization. RCD is the percentage of subjects with a best overall response of CR, PR or SD among the analysis population. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 67 months
| Intervention | Percentage of Participants (Mean) |
|---|
| Panitumumab Plus Chemotherapy | 80.77 |
| Chemotherapy Alone | 72.55 |
Progression Free Survival (PFS) During the Second-line Treatment Phase
The time from the first dose of panitumumab monotherapy to the date of first disease progression determined by the investigators per modified RECIST v1.0, or death within 60 days after the last evaluable tumor assessment or the second-line first dose date (whichever is later) during the second-line treatment phase. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 57 months
| Intervention | Months (Median) |
|---|
| Chemotherapy Alone | 4.2 |
Overall Survival (OS) for the Second-line Treatment
Time from the first dose of panitumumab monotherapy to the date of death during the entire study (NCT00454779)
Timeframe: Until death, up to 57 months
| Intervention | Months (Median) |
|---|
| Chemotherapy Alone | 8.5 |
Progression Free Survival (PFS) During the First-line Treatment Phase
The time from the date of randomization to the date of first disease progression determined by the investigators per modified RECIST v1.0, or death within 60 days after the last evaluable tumor assessment or randomization date (whichever is later) during the first-line treatment phase. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 67 months
| Intervention | Months (Median) |
|---|
| Panitumumab Plus Chemotherapy | 6.9 |
| Chemotherapy Alone | 5.5 |
Overall Survival (OS) for the First-line Treatment
Time from the date of randomization to the date of death during the entire study (NCT00454779)
Timeframe: Until death, up to 67 months
| Intervention | Months (Median) |
|---|
| Panitumumab Plus Chemotherapy | 12.9 |
| Chemotherapy Alone | 13.8 |
Duration of Response (DOR) During the Second-line Treatment Phase
Time from the first CR or PR to the first observed disease progression by a modified RECIST v1.0. Subjects not meeting the criteria for progression by the analysis data cutoff date will be censored at their last evaluable disease assessment date. (NCT00454779)
Timeframe: Every 6 weeks until disease progression or death, up to 57 months
| Intervention | Months (Median) |
|---|
| Chemotherapy Alone | NA |
Partial Response Rate in Both Groups of Patients.
Objective tumor response was evaluated radiogically using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0. For target lesions: Complete Response (CR) disappearance of all target lesions; Partial Response (PR) >= 30% decrease in the sum of the longest diamter of target lesions; Overall Response (OR) = CR+PR (NCT00459043)
Timeframe: 3 years
| Intervention | percentage of participants (Number) |
|---|
| 1Docetaxel Single Agent | 7 |
| 2 Combination Docetaxel and ZD6474 | 13 |
Overall Survival
(NCT00459043)
Timeframe: 3 years
| Intervention | weeks (Median) |
|---|
| 1Docetaxel Single Agent | 26.8 |
| 2 Combination Docetaxel and ZD6474 | 24.1 |
Progression Free Survival
Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) as a 20% increase in the sumof the longest diameter of target lesions, or a measurable increase in a non-target lesion or the appearance of new lesions (NCT00459043)
Timeframe: 3 years
| Intervention | weeks (Median) |
|---|
| 1Docetaxel Single Agent | 3.21 |
| 2 Combination Docetaxel and ZD6474 | 9 |
Response Based on PET Scan
Patients were scanned using Positron Emission Tomography (PET) before and after receiving single agent RAD001. Patients were classified as having partial metabolic response, stable metabolic disease, or progressive metabolic disease based on changes in PET imaging from baseline to post-treatment. A positive FDG-PET for the purposes of this study consisted of a visualized area of abnormal increased FDG uptake that matched the anatomic location of an abnormality seen on bone scan or CT. Metabolic response was assessed for percent change in SUVmax according to the criteria of the European Organization for Research and Treatment of Cancer (EORTC) : partial metabolic response (PMR) ≤ -25%; stable metabolic disease (SMD) -25% + 25%; progressive metabolic disease (PMD) > 25%. (NCT00459186)
Timeframe: 10 to 14 days after study entry
| Intervention | percentage of participants (Number) |
|---|
| Partial Metabolic Response | Stable Metabolic Disease | Progressive Metabolic Disease |
|---|
| RAD001 Followed by RAD001 + Docetaxel | 22 | 67 | 11 |
Number of Patients Free of Dose Limiting Toxicity
"A dose limiting toxicity was defined as an adverse event or laboratory abnormality that occurs to patients on the Phase I portion of the trial, during the first 21 days following the first dose of RAD001/docetaxel during cycle 1, judged to be related to RAD001/docetaxel and meeting any of the following criteria:~Hematologic Toxicity:~CTCAE grade 4 neutropenia > 7 days or any Grade 3 or 4 neutropenia with fever Or CTCAE grade 3 or 4 thrombocytopenia > 7 days~Non-hematologic toxicity:~The occurrence of non-hematologic CTCAE grade 3 or 4 adverse events will be considered dose limiting, except for the following:~CTCAE grade 3 nausea or grade 3 or 4 vomiting CTCAE grade 3 or 4 vomiting will only be considered dose limiting if it occurs despite the use of standard anti-emetics.~CTCAE grade 3 or 4 fever identified with a source (i.e. infection, tumor)~CTCAE grade 3 or 4 alkaline phosphatase." (NCT00459186)
Timeframe: 21 days
| Intervention | participants (Number) |
|---|
| RAD001 Followed by RAD001 + Docetaxel | 14 |
Percentage of Participants With Surgical Complications (From Mastectomy, Lumpectomy, and Axillary Staging Procedures) (Cohort A)
The percentage of patients with surgical complications (from mastectomy, lumpectomy, and axillary staging procedures). (NCT00464646)
Timeframe: 2-4 weeks after surgery and at 9 and 12 months from study entry
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A | 37 |
Number of Patients With Pathological Complete Response (pCR) in the Breast and Nodes for Patients With HER2-positive LABC Following Neoadjuvant Treatment (Cohort A)
The determination of pCR is performed by the local pathologist following examination of tissue (breast and nodes)removed at the time of surgery. The outcome measure is the number of participants with no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or SNs identified after neoadjuvant chemotherapy. (NCT00464646)
Timeframe: Assessed at time of surgery on average at 8 months
| Intervention | participants (Number) |
|---|
| Cohort A | 34 |
Number of Participants With no Histologic Evidence of Invasive Tumor Cells in the Surgical Breast Specimen.
The determination of pCR will be performed by the local pathologist following examination of tissue (breast and nodes) removed at the time of surgery. (NCT00464646)
Timeframe: Assessed at the time of surgery
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A | 36 |
| Cohort B | 0 |
Overall Survival
Death from any cause during the 5 years from study entry. (NCT00464646)
Timeframe: From the first dose of study therapy until the date of death or for a maximum of five (5) years from study entry
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A | 12 |
| Cohort B | 0 |
Recurrence-free Survival
To determine the five-year RFS. (NCT00464646)
Timeframe: From the first dose of study therapy until the date of recurrence or for a maximum of five (5) years from study entry
| Intervention | percentage of patients (Number) |
|---|
| Cohort A | 75.97 |
| Cohort B | 89.66 |
Clinical Complete Response (cCR)
cCR following the last dose of docetaxel (Cohort A). cCR is detemined by tumor measurement by physical exam at baseline: target lesions greater than or equal to 2.0 cm; non-target lesions greater than or equal to 2.0 cm. cCR assessment at other timepoints: resolution of all target and non-target lesions identified at baseline, and no new lesions or other signs of disease progression. (NCT00464646)
Timeframe: Determined at baseline, 2-3 weeks after the last EC dose, 2-4 weeks after last Docetaxel dose-before surgery.
| Intervention | percentage of patients (Number) |
|---|
| Cohort A | 61.43 |
Grade 3 and 4 Toxicities, Including Toxicities Associated With Radiation Therapy(RT)
(NCT00464646)
Timeframe: Before each cycle of pre-op Rx; 2-4 wks after the last docetaxel dose; 2-4 wks post surgery (Cohort A); every 6 wks during post-op Rx (Cohort A); every 6 wks during targeted therapy alone (Cohort B); RT complications assessed at 12 mos from study entry
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A | 55 |
| Cohort B | 22 |
Number of Participants With Cardiac Events
The number of cardiac events defined as NYHA Class III/IV CHF and cardiac death.To determine the rate of cardiac events (NYHA Class III/IV CHF and cardiac death) of a regimen of EC followed by THA when administered to: Cohort A as neoadjuvant therapy for HER-2 positive locally advanced (clinical stage IIIA, IIIB or IIIC breast cancer or Cohort B as adjuvant therapy for resected HER2-positive pN2 or pN3 (pathologic stage III) breast cancer. The number of participants with one or more cardiac events are being reported. (NCT00464646)
Timeframe: Cohort A: Baseline, post-treatment with EC, 2-4 weeks after surgery, and 9, 12, 15, and 18 months from study entry. Cohort B: Baseline, post-treatment with EC, 2-3 weeks after the last dose of docetaxel, and 6, 9, 12, 15, and 18 months from study entry.
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A | 4 |
| Cohort B | 0 |
Part I: Pharmacokinetic (PK) Parameter: Maximum Observed Drug Concentration During a Dosing Interval at Steady State (Cmax,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
Cmax,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). (NCT00466440)
Timeframe: Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose
| Intervention | nanomole per liter (nmol/L) (Geometric Mean) |
|---|
| Enzastaurin | LSN326020 | Total Analyte |
|---|
| Enzastaurin 500 mg QD + Docetaxel 75 mg/m^2 + Prednisone | 778 | 667 | 1450 |
,| Enzastaurin 500 mg QD Alone | 870 | 664 | 1540 |
Part 2: Duration of Response
Duration of response is defined as the time from date of objective response to progressive disease (PD) or death or prostate-specific androgen (PSA) returning to at least 50% from original baseline value. (NCT00466440)
Timeframe: First objective response to PD/death/PSA returning to 50% or more than the original baseline value (up to 616 days)
| Intervention | days (Median) |
|---|
| Part 2: Docetaxel + Prednisone + Enzastaurin | 231 |
| Part 2: Docetaxel + Prednisone + Placebo | 201 |
Pharmacokinetic (PK) Parameter: Area Under the Concentration Versus Time Curve During 1 Dosing Interval at Steady State (AUCτ,ss) of Enzastaurin, LSN326020, and Total Analyte (Enzastaurin + LSN326020)
AUCτ,ss was calculated using concentration versus time data of enzastaurin, LSN326020, and total analyte (enzastaurin + LSN326020). Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). (NCT00466440)
Timeframe: Part 1: Cycle 1, Day 21 - predose 2, 4, 6, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 2, 3, 4, 8, and 24 hours postdose; Part 2: Cycle 2, Day 1 - predose, 1-3, and 4-9 hours postdose
| Intervention | nanomole*hour per liter (nmol*hr/L) (Geometric Mean) |
|---|
| Enzastaurin | LSN326020 | Total Analyte |
|---|
| Enzastaurin 500 mg QD Alone | 12900 | 15200 | 28700 |
,| Enzastaurin 500 mg QD+Docetaxel 75 mg/m^2+Prednisone (Part 1) | 13100 | 15700 | 29000 |
,| Enzastaurin 500 mg QD+Docetaxel 75 mg/m^2+Prednisone (Part 2) | 20800 | 24800 | 47800 |
Percentage of Participants Exhibiting a Decline in Prostate-Specific Androgen (PSA) From Baseline ≥30% Within First 3 Months of Treatment
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. Decline in PSA of ≥30% from baseline within the first 3 months of treatment was calculated. (NCT00466440)
Timeframe: Baseline up to 3 months
| Intervention | percentage of participants (Number) |
|---|
| Part 1: Docetaxel + Prednisone + Enzastaurin | 69.2 |
| Part 2: Docetaxel + Prednisone + Enzastaurin | 60.9 |
| Part 2: Docetaxel + Prednisone + Placebo | 72.5 |
Part 2: Overall Survival (OS)
Overall survival (OS) time is defined as the time from the date of diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date. (NCT00466440)
Timeframe: Baseline to death (up to 642 days)
| Intervention | days (Median) |
|---|
| Part 2: Docetaxel + Prednisone + Enzastaurin | 462 |
| Part 2: Docetaxel + Prednisone + Placebo | 448 |
Part 2: Progression Free Survival (PFS)
PFS was defined as the time from the date of study enrollment to the first date of objectively determined progressive disease (PD) or death from any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). PD is ≥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 1 or more new lesions. For participants not known to have died and who did not have PD, PFS was censored at the date of the last progression-free assessment. For participants who received subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to disease progression or death, PFS was censored at the date of last progression-free assessment prior to the initiation of post-discontinuation systemic anticancer therapy. No participant completed a full cycle of therapy and thus no formal analysis was performed. (NCT00466440)
Timeframe: Baseline to measured PD (up to 487 days)
| Intervention | Days (Median) |
|---|
| Part 2: Docetaxel + Prednisone + Enzastaurin | 229 |
| Part 2: Docetaxel + Prednisone + Placebo | 213 |
Pharmacokinetic (PK) Parameter: Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-∞]) of Docetaxel
AUC(0-∞) was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). (NCT00466440)
Timeframe: Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Docetaxel 75 mg/m^2 Alone | 2350 |
| Enzastaurin 500 mg QD + Docetaxel 75 mg/m^2 + Prednisone | 1750 |
Pharmacokinetic (PK) Parameter: Maximum Plasma Concentration (Cmax) of Docetaxel
Cmax was calculated using concentration versus time data of docetaxel. Data are reported as Geometric Mean and Geometric Coefficient of Variation (%). (NCT00466440)
Timeframe: Part 1: Cycle 1, Day 1 - predose 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose; Cycle 2, Day 1 - predose, 0.5, 1, 1.5, 2, 3, 4, 8, and 24 hours postdose
| Intervention | nanograms per millimeter (ng/mL) (Geometric Mean) |
|---|
| Docetaxel 75 mg/m^2 Alone | 2230 |
| Enzastaurin 500 mg QD + Docetaxel 75 mg/m^2 + Prednisone | 1840 |
Part 2: Percentage of Participants With Objective Tumor Response (Response Rate)
Response using Response Evaluation Criteria In Solid Tumors (RECIST). 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. Objective response rate (%)=number of objective responders divided by the number of participants qualified for efficacy analysis *100, where objective responders are those participants who have met criteria either for CR or PR. (NCT00466440)
Timeframe: Baseline up to 3 years
| Intervention | percentage of participants (Number) |
|---|
| Part 2: Docetaxel + Prednisone + Enzastaurin | 15.2 |
| Part 2: Docetaxel + Prednisone + Placebo | 15.0 |
Prostate-Specific Androgen (PSA) Velocity at 3 Months
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity. (NCT00466440)
Timeframe: Baseline up to 3 months
| Intervention | ug/L per month (Mean) |
|---|
| Part 1: Docetaxel + Prednisone + Enzastaurin | -0.45 |
| Part 2: Docetaxel + Prednisone + Enzastaurin | -0.30 |
| Part 2: Docetaxel + Prednisone + Placebo | -0.45 |
Number of Participants With Adverse Events (AEs)
A listing of serious AEs (SAEs) and all other non-serious AEs is included in the Reported Adverse Event Module. (NCT00466440)
Timeframe: Baseline through 3 years
| Intervention | Participants (Count of Participants) |
|---|
| SAEs | Other Non-Serious AEs |
|---|
| Part 1: Docetaxel + Prednisone + Enzastaurin | 8 | 14 |
,| Part 2: Docetaxel + Prednisone + Enzastaurin | 16 | 47 |
,| Part 2: Docetaxel + Prednisone + Placebo | 14 | 41 |
Prostate-Specific Androgen (PSA) Velocity at 2 Months
PSA is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is considered the most effective test currently available for the early detection of prostate cancer. PSA velocity is computed for each participant by means of linear regression on the logarithm of PSA. The linear regression fits a line through the logarithm of the PSA value on the y-axis, and the time from baseline on the x-axis with the baseline PSA value at time zero. The resulting slope is PSA velocity. (NCT00466440)
Timeframe: Baseline up to 2 months
| Intervention | microgram per liter (ug/L) per month (Mean) |
|---|
| Part 1: Docetaxel + Prednisone + Enzastaurin | -0.56 |
| Part 2: Docetaxel + Prednisone + Enzastaurin | -0.29 |
| Part 2: Docetaxel + Prednisone + Placebo | -0.55 |
Percentage of Participants With Clinical Benefit According to RECIST Guidelines
Clinical benefit was defined as stable disease (SD) for 6 months or longer, or a confirmed overall response of CR or PR. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the beginning of treatment. For NTLs, SD was synonymous with incomplete response and defined as the persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Taxane | 70.7 |
Overall Survival
The time, in months, from BL to death due to any cause. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 52 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment
| Intervention | months (Median) |
|---|
| Trastuzumab, Taxane | 25.0 |
Percentage of Participants With Treatment Failure
Treatment failure was defined as the time from first study drug infusion to failure. Failure was defined as any of the following: PD, death, withdrawal due to adverse event (AE) or lab abnormality, or refusal of treatment. Participants were censored at the last date recorded in the case report form (CRF) or the date of withdrawal. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Taxane | 95.1 |
Progression-Free Survival
The time, in months, from BL to PFS event. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | months (Median) |
|---|
| Trastuzumab, Taxane | 8.0 |
Progression-free Survival (PFS) - Percentage of Participants With Progressive Disease
PFS was defined as the time from day of first study drug infusion until death or PD. Participants were censored at the date of the last tumor assessment. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Taxane | 87.8 |
Time to Treatment Failure
The time, in months, from BL to treatment failure. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | months (Median) |
|---|
| Trastuzumab, Taxane | 8.0 |
Duration of Response - Percentage of Participants With Progressive Disease or Death
Duration of response was defined as the time from first confirmed CR or PR until death or progressive disease (PD). For TLs, PD was defined as at least a 20% increase in the SLD of the TL, taking as reference the smallest SLD recorded since the beginning of treatment or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of one or more new lesions or unequivocal progression of existing non target non-measurable lesions. Participants were censored at the date of the last tumor assessment. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Taxane | 88.0 |
Duration of Response
The time, in months, from when the response (CR or PR) was first noted until the date of documented PD, death, or withdrawal, whichever occurred first. Participants were censored at the date of the last tumor assessment. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | months (Median) |
|---|
| Trastuzumab, Taxane | 8.0 |
Overall Survival - Percentage of Participants Who Died
OS was defined as the time from the date of enrollment to the date of death due to any cause. Participants were censored at the last date recorded in the CRF. (NCT00475670)
Timeframe: BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 5 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Taxane | 63.4 |
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Guidelines
CR was defined for target lesions (TLs) as the disappearance of all lesions, and for nontarget lesions (NTLs) as the disappearance of all nontarget nonmeasurable lesions. PR was defined for TLs as at least a 30 percent (%) decrease from baseline (BL) in the sum of longest diameter (SLD) of TLs. 95% confidence interval for one-sample binomial using Pearson-Clopper method. (NCT00475670)
Timeframe: Baseline (BL); Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Taxane | 61.0 |
Overall Tumor Response
Overall tumor response is defined as the percentage of participants with a confirmed complete or partial tumor response per Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is defined as the disappearance of all target lesions. CR could only be declared if all target and non-target lesions had disappeared. Partial response (PR) is defined as a decrease of 30% or greater in the sum of the longest diameter of target lesions. (NCT00479856)
Timeframe: from start of treatment and every 6 weeks (wks) until Wk 12, then every 12 wks thereafter through the end of treatment (~95 wks; dependent on when participant discontinued study therapy due to disease progression, death, adverse event, of other reason)
| Intervention | percentage of participants (Number) |
|---|
| Lapatinib + Chemotherapy | 33.3 |
The Number of Patients That Experience Evidence of Local Recurrence
The number of patients that have local disease recurrence by imaging and clinical findings. (NCT00480857)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel | 0 |
The Percentage of Patients That Experience at Least 1 Grade 1, 2, 3 and 4 Toxicities
"To determine the rates of toxicities among patients treated with concurrent weekly docetaxel (TAXOTERE) and salvage prostate bed radiation therapy.~G1 events are considered mild. G2 events are considered moderate G3 events are considered severe G4 events are considered life-threatening" (NCT00480857)
Timeframe: 4 years
| Intervention | percentage of patients (Number) |
|---|
| Patients that experience at least 1 G1 toxicity | Patients that experience at least 1 G2 toxicity | Patients that experience at least 1 G3 toxicity | Patients that experience at least 1 G4 toxicity |
|---|
| Docetaxel | 79 | 50 | 58 | 11 |
Percentage of Patients Alive Without Progression at 4 Years
The primary objective is to assess the 4-year progression free proportion of patients treated with concurrent weekly docetaxel (TAXOTERE) and salvage prostate bed radiation therapy among patients with biochemical recurrence after radical prostatectomy. (NCT00480857)
Timeframe: 4 years
| Intervention | percentage of patients (Number) |
|---|
| Docetaxel | 42 |
The Number of Patients Alive
The number of patients alive at 4 years. (NCT00480857)
Timeframe: 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel | 18 |
Number of Patients That Achieve a Post-radiotherapy PSA Nadir of 0.1 ng/mL or Less
To determine the rates of complete biochemical response (as defined by achievement of a post-radiotherapy PSA nadir of 0.1 ng/mL or less) after concurrent weekly docetaxel (TAXOTERE) and salvage prostate bed radiation therapy. (NCT00480857)
Timeframe: 4 years
| Intervention | patients (Number) |
|---|
| Docetaxel | 12 |
Number of Participants With a Complete Response as Measured by Serum PSA Less Than 0.2 ng/ml
Complete response rate, as measured by PSA and defined as a PSA ≤0.2 ng/ml in PSA-relapsed, hormone-sensitive patients treated with docetaxel. (NCT00482274)
Timeframe: While receiving study treatment (approximately 6 months)
| Intervention | participants (Number) |
|---|
| Docetaxel | 1 |
Participant Response Rate
Response rate to regimen defined as the number of complete or partial response divided by the total number of participants treated. Tumor response defined by Response Evaluation Criteria In Solid Tumors (RECIST). All complete and partial responses confirmed by a second assessment six weeks later. (NCT00485485)
Timeframe: At 6 weeks reconfirmed 6 weeks later
| Intervention | Participants (Number) |
|---|
| Imatinib Mesylate + Docetaxel | 7 |
Overall Survival
The Kaplan-Meier product limit method will be used to estimate the median overall survival (NCT00488982)
Timeframe: Up to 7 years
| Intervention | months (Median) |
|---|
| Docetaxel and Observation | 14 |
| Docetaxel and GM-CSF | 28.4 |
| Overall Survival | 15.6 |
Cumulative Duration of Time on and Off Docetaxel-based Therapy
Median percentage of time will be calculated to summarize the total duration of chemotherapy and amount of docetaxel/prednisone administered while the patient is on study. The same results will be tabulated for each. For the on-chemotherapy period: will be estimated from the date of starting protocol therapy; if a patient received docetaxel on day 2 of a cycle, he will be considered to have received a full 21 days on therapy. For the off-chemotherapy period: will be calculated from the date of starting the observation or GM-CSF period to the date of resuming chemotherapy (NCT00488982)
Timeframe: Up to 7 years
| Intervention | months (Median) |
|---|
| Docetaxel and Observation OFF Chemotherapy | 24.7 |
| Docetaxel and GM-CSF OFF Chemotherapy | 30.9 |
| Docetaxel + Observation ON Chemotherapy | 8.3 |
| Docetaxel and GM-CSF ON Chemotherapy | 7.6 |
Time to Progression
The Kaplan-Meier product limit method with 95% confidence intervals will be used to estimate the median time to disease progression during initial course of randomized treatment (NCT00488982)
Timeframe: Up to 7 years
| Intervention | months (Median) |
|---|
| Docetaxel and Observation | 1.5 |
| Docetaxel and GM-CSF | 3.3 |
Number of Participants With PSA Response to Successive Series of Chemotherapy
PSA partial response is defined by at least a 50% decline from PSA value from the baseline measurement to 12 weeks of protocol therapy. The decline must be confirmed by a second PSA value obtained 4 or more weeks later For those patients whose PSA have decreased but has not reached response criteria defined above, progressive disease is defined as 25% increase over the nadir PSA value provided that the increase is at least 5ng/mL and is confirmed. (NCT00488982)
Timeframe: Up to 6 years
| Intervention | Participants (Count of Participants) |
|---|
| PSA response to Course 2 chemotherapy | PSA response to Course 3 chemotherapy |
|---|
| Docetaxel and GM-CSF | 8 | 0 |
,| Docetaxel and Observation | 4 | 1 |
Number of Participants With Hematology Abnormalities by Worst Grade Per National Cancer Institute Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Grade (GR)1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. White blood cell (WBC):GR1=NCT00490646)
Timeframe: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
| Intervention | participants (Number) |
|---|
| WBC Grade 1 (n=24; n=22) | WBC Grade 2 (n=24; n=22) | WBC Grade 3 (n=24; n=22) | WBC Grade 4 (n=24; n=22) | ANC Grade 1 (n=23; n=23) | ANC Grade 2 (n=23; n=23) | ANC Grade 3 (n=23; n=23) | ANC Grade 4 (n=23; n=23) | Platelet Count Grade 1 (n=24; n=23) | Platelet Count Grade 2 (n=24; n=23) | Platelet Count Grade 3 (n=24; n=23) | Platelet Count Grade 4 (n=24; n=23) | Hemoglobin Grade 1 (n=24; n=23) | Hemoglobin Grade 2 (n=24; n=23) | Hemoglobin Grade 3 (n=24; n=23) | Hemoglobin Grade 4 (n=24; n=23) |
|---|
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 1 | 1 | 15 | 4 | 0 | 0 | 3 | 19 | 3 | 0 | 0 | 0 | 12 | 8 | 1 | 0 |
,| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 6 | 7 | 8 | 1 | 2 | 4 | 8 | 6 | 9 | 0 | 0 | 1 | 14 | 8 | 0 | 0 |
Percentage of Participants With Objective Response (OR; Assessed by Response Evaluation Criteria in Solid Tumors [RECIST] Version 1.1)
Percentage of participants with best overall response (BOR) of either complete response (CR) or partial response (PR) according to RECIST version 1.1 as determined by the investigator. 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 (LD) of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. A two-sided confidence interval (CI) was computed using the Clopper-Pearson method. (NCT00490646)
Timeframe: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 60.0 |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 52.0 |
Progression Free Survival (PFS)
"Time in months from randomization until first date of documented progressive disease (PD) or death from any cause without prior documentation of progression. PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall.~Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method." (NCT00490646)
Timeframe: From randomization until the first date of documented progressive disease (PD) or death from any cause without prior documentation of progression (maximum participant PFS of 39.7 months).
| Intervention | months (Median) |
|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 11.3 |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 13.0 |
Number of Participants With Serum Chemistry Abnormalities by Worst Grade Per National Cancer Institure Common Terminology Criteria Adverse Events (NCI CTCAE), Version 3.0
Grading: NCI CTCAE, Version 3.0. GR1=mild, GR2=moderate, GR3=severe, GR4=life threatening or disabling. Normal ranges provided by local laboratory and may also vary by age and sex. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST): GR1=>ULN-2.5*ULN; GR2=>2.5-5.0*ULN; GR3=>5.0-20.0*ULN; GR4=>20.0*ULN. Total bilirubin: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3-10*ULN, GR4=>10*ULN. Creatinine: GR1=>ULN-1.5*ULN, GR2=>1.5-3.0*ULN, GR3=>3.0-6.0*ULN, GR4=>6.0*ULN. ULN=upper limit of normal. (NCT00490646)
Timeframe: Prior to every cycle of therapy (i.e. before starting of every 21 day or 3 week cycle; maximum time that any participant was on therapy was 108 weeks.)
| Intervention | participants (Number) |
|---|
| ALP Grade 1 (n=23; n=23) | ALP Grade 2 (n=23; n=23) | ALP Grade 3 (n=23; n=23) | ALP Grade 4 (n=23; n=23) | ALT Grade 1 (n=24; n=23) | ALT Grade 2 (n=24; n=23) | ALT Grade 3 (n=24; n=23) | ALT Grade 4 (n=24; n=23) | AST Grade 1 (n=24; n=23) | AST Grade 2 (n=24; n=23) | AST Grade 3 (n=24; n=23) | AST Grade 4 (n=24; n=23) | Total Bilirubin Grade 1 (n=24; n=23) | Total Bilirubin Grade 2 (n=24; n=23) | Total Bilirubin Grade 3 (n=24; n=23) | Total Bilirubin Grade 4 (n=24; n=23) | Creatinine Grade 1 (n=24; n=23) | Creatinine Grade 2 (n=24; n=23) | Creatinine Grade 3 (n=24; n=23) | Creatinine Grade 4 (n=24; n=23) |
|---|
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 8 | 1 | 0 | 0 | 15 | 0 | 1 | 0 | 11 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
,| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 11 | 0 | 0 | 0 | 10 | 3 | 0 | 0 | 13 | 0 | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 2 | 0 | 0 |
Duration of Response
"Period measured in months from time that measurement criteria were first met for CR or PR until first date of documented PD or death from any cause without prior documentation of progression.~PD=≥20% increase in sum of LD of target lesions in reference to smallest sum LD recorded at or following baseline or unequivocal progression of existing non-target lesion(s) overall. Refer to Outcome Measure 1 for definitions of CR and PR. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by Brookmeyer and Crowley method." (NCT00490646)
Timeframe: From the date of first PR or CR assessment to the date of documented progressive disease or death without prior documentation of progression (maximum participant duration of response of 38 months.)
| Intervention | months (Median) |
|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 11.5 |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 16.5 |
Time to Response
"Time to response was defined as the time in weeks from randomization until the measurement criteria are first met for a CR or PR, whichever is recorded first.~CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Estimated by the Kaplan-Meier product limit method. A two-sided 95% CI for median duration was computed by the Brookmeyer and Crowley method." (NCT00490646)
Timeframe: From randomization every 6 weeks for first 12 months and thereafter every 3 months until CR or PR whichever was recorded first (maximum participant time to response of 18.4 weeks.)
| Intervention | weeks (Median) |
|---|
| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 10.1 |
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 7.3 |
Number of Participants With Death as Outcome, Serious Adverse Events (SAEs), Adverse Events (AEs), and AEs Leading to Discontinuation of Study Therapy Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 3.0
AE: New untoward medical occurrence or worsening of a preexisting medical condition that does not have causal relationship with this treatment. SAE: Untoward medical event that at any dose: results in death, persistent or significant disability/incapacity, drug dependency/abuse; life-threatening, an important medical event, a congenital anomaly/birth defect; requires inpatient hospitalization/prolongs existing hospitalization. Grade 3=Severe; and Grade 4=Life-threatening or disabling. GR=Grade. (NCT00490646)
Timeframe: Assessed from the date of first dose until at least 30 days after the last dose of study drug (maximum time that any participant was on therapy was 108 weeks.)
| Intervention | participants (Number) |
|---|
| All deaths | Death within 30 days of last dose of study therapy | SAEs (Any Grade) | SAEs (Grades 3-4) | Drug-related SAEs (Any Grade) | Drug-related SAEs (Grades 3-4) | AEs (Any Grade) | AEs (Grades 3-4) | Drug-related AEs (Any Grade) | Drug-related AEs (Grades 3-4) | AEs leading to discontinuation of therapy (Any GR) | AEs leading to discontinuation of therapy (GR 3-4) | Drug-related peripheral neuropathy (Any Grade) | Drug-related peripheral neuropathy (Grades 3-4) |
|---|
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 1 | 0 | 13 | 12 | 10 | 8 | 24 | 23 | 24 | 22 | 9 | 4 | 12 | 0 |
,| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 1 | 1 | 6 | 4 | 3 | 2 | 24 | 19 | 24 | 18 | 5 | 2 | 16 | 2 |
Number of Participants With Best Overall Response (BOR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
BOR was the best response recorded from the start of treatment until disease progression or 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 LD of all lesions. CR and PR criteria should be met again after 4 weeks and before 6 weeks after initial assessment. Stable disease (SD)=Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. Refer to Outcome Measure 3 for definition of PD. (NCT00490646)
Timeframe: Assessed every 6 weeks from initiation of study therapy up to 12 months; then every 3 months until disease progression (maximum time that any participant was on therapy was 108 weeks).
| Intervention | participants (Number) |
|---|
| Complete response | Partial response | Stable disease | Progressive disease | Unable to determine (UTD; Death due to toxicity) | UTD (reason other than toxicity or progression) | Never treated |
|---|
| Trastuzumab 2 mg/kg + Docetaxel 100 mg/m^2 IV | 2 | 11 | 9 | 1 | 0 | 1 | 1 |
,| Trastuzumab 2 mg/kg + Ixabepilone 40 mg/m^2 IV | 3 | 12 | 6 | 1 | 1 | 1 | 1 |
OS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
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. (NCT00493649)
Timeframe: 2 years
| Intervention | probability of overall survival (Number) |
|---|
| cMYC-amplified Group | 0.990 |
| cMYC-nonamplified Group | 0.991 |
Disease-free Survival (DFS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up. (NCT00493649)
Timeframe: 2 years
| Intervention | probability of disease-free survival (Number) |
|---|
| TOP2A-amplified Group | 0.978 |
| TOP2A-nonamplified Group | 0.979 |
DFS by cMyc Expression in This Population of HER2+ ESBC Patients Treated With TC+H.
DFS was measured from the date of registration to either the date the patient was first recorded as having disease recurrence, or the date of death due to any causes before recurrence. If a patient had not recurred or died, DFS was censored at the date of last follow-up. (NCT00493649)
Timeframe: 2 years
| Intervention | probability of disease-free survival (Number) |
|---|
| cMYC-amplified Group | 0.968 |
| cMYC-nonamplified Group | 0.981 |
Overall Survival (OS) Rate at 2 Years in TOP2A-amplified and in TOP2A-nonamplified HER2+ ESBC Patients Treated With TC+H.
OS is measured from the date of registration 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. (NCT00493649)
Timeframe: 2 years
| Intervention | probability of overall survival (Number) |
|---|
| TOP2A-amplified Group | 0.995 |
| TOP2A-nonamplified Group | 0.988 |
3-year DFS Stratified by TOP2A Among TC Arm
To evaluate DFS among TC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer. (NCT00493870)
Timeframe: 3 years from randomization into study
| Intervention | percentage of participants (Number) |
|---|
| Amplification | 85.1 |
| Deletion | 82.8 |
| Normal | 93.8 |
3-year DFS-DCIS, OS and RFI Among Per-protocol Patients.
To compare disease-free survival-ductal carcinoma in situ (DFS-DCIS),overall survival (OS) and recurrence free interval (RFI) of TC with TAC among per protocol patients. (NCT00493870)
Timeframe: 3 years from randomization into study
| Intervention | percentage of participants (Number) |
|---|
| 3-year DFS-DCIS | 3-year OS | 3-year RFI |
|---|
| TAC Arm | 93.0 | 96.8 | 94.5 |
,| TC Arm | 91.1 | 96.8 | 92.1 |
3-year DFS Stratified by TOP2A Among TAC Arm
To evaluate DFS among TAC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer. (NCT00493870)
Timeframe: 3 years from randomization into study
| Intervention | percentage of participants (Number) |
|---|
| Amplification | 100 |
| Deletion | 90.9 |
| Normal | 93.2 |
Number and Frequency of Participants by TOP2A Status by Study Treatment
To evaluate the effectiveness of TC and TAC in TOP2A altered (amplified, deleted, or overexpressed at the protein level) early stage HER2-negative breast cancer (NCT00493870)
Timeframe: 10 years (from baseline to end of study participation)
| Intervention | Participants (Count of Participants) |
|---|
| Amplification | Deletion | Normal |
|---|
| TAC Arm | 14 | 128 | 489 |
,| TC Arm | 14 | 131 | 479 |
3-year DFS-DCIS, OS and RFI Among Analyzed ITT Patients
To compare disease-free survival-ductal carcinoma in situ (DFS-DCIS),overall survival (OS) and recurrence free interval (RFI) of TC with TAC. DFS-DCIS, defined as the time from the date of randomization to local recurrence following mastectomy, local recurrence in the ipsilateral breast following lumpectomy (invasive or non-invasive), regional recurrence, distant recurrence, contralateral breast cancer (invasive or non-invasive), second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colorectal carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. Patients who have not had any such event at the time of data analysis will be censored at the last date they were known to be event-free. (NCT00493870)
Timeframe: 3 years from randomization into study
| Intervention | percentage of participants (Number) |
|---|
| 3-year DFS-DCIS | 3-year OS | 3-year RFI |
|---|
| TAC Arm | 93.0 | 96.8 | 94.5 |
,| TC Arm | 90.9 | 96.8 | 91.9 |
3-year Invasive Disease-free Survival (IDFS) Among Per-protocol Patients
The primary objective of the study is to compare the 3-year invasive disease-free survival (IDFS) of adjuvant TC versus TAC as treatment for early stage HER2-negative breast cancer among per-protocol patients. Per-protocol only includes those patients who were randomized and received treatment as outlined in the protocol. (NCT00493870)
Timeframe: 3 years from randomization into study
| Intervention | percentage of participants (Number) |
|---|
| TC Arm | 91.3 |
| TAC Arm | 93.2 |
3-year Invasive Disease-free Survival (IDFS) Among Analyzed ITT Patients
The primary objective of the study is to compare the 3-year invasive disease-free survival (IDFS) of adjuvant TC versus TAC as treatment for early stage HER2-negative breast cancer among analyzed ITT patients. ITT patients are all patients who were randomized, whether or not they followed protocol. IDFS, defined as the time from the date of randomization to local recurrence following mastectomy, invasive local recurrence in the ipsilateral breast following lumpectomy, regional recurrence, distant recurrence, invasive contralateral breast cancer, second primary cancer (other than squamous or basal cell carcinoma of the skin, melanoma in situ, carcinoma in situ of the cervix, colorectal carcinoma in situ, or lobular carcinoma in situ of the breast), or death from any cause prior to recurrence or second primary cancer. Patients who have not had any such event at the time of data analysis will be censored at the last date they were known to be event-free. (NCT00493870)
Timeframe: 3 years from randomization into study
| Intervention | percentage of participants (Number) |
|---|
| TC Arm | 91.1 |
| TAC Arm | 93.2 |
Number of Patients With a Disease Progression Event
Number of patients with objective disease progression or death (by any cause in the absence of objective progression) (NCT00494481)
Timeframe: RECIST tumour assessments carried out at screening (within 3 weeks before the 1st dose) and then as per site clinical practice until objective progression. The only additional mandatory RECIST assessment is at the point of data cut-off
| Intervention | Participants (Number) |
|---|
| Vandetanib Plus Docetaxel | 24 |
| Placebo Plus Docetaxel | 18 |
Number of Patients With an Objective Disease Progression Event
Number of patients with objective disease progression or death (by any cause in the absence of objective progression) (NCT00498797)
Timeframe: RECIST tumour assessments carried out at screening and then as per site clinical practice until objective progression. The only additional mandatory tumour assessment visit is at the point of data cut-off (21 July 2007 or up to 7 days in advance of DCO)
| Intervention | Participants (Number) |
|---|
| Vandetanib | 28 |
| Placebo | 26 |
Prostate Specific Antigen (PSA) Response
Prostate Specific Antigen (PSA) response was defined as a reduction of at least 50% from baseline at any assessment, confirmed by a second assessment 2-4 weeks after the initial response (NCT00498797)
Timeframe: PSA measurements were to be performed at screening, at baseline (>2 weeks after screening) and every 3 weeks during the study. Any response was to be confirmed 2-4 weeks after the initial assessment of a 50% fall in PSA from baseline
| Intervention | Participants (Number) |
|---|
| Vandetanib | 17 |
| Placebo | 29 |
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
| Intervention | estimated percentage of participants (Number) |
|---|
| E. Dual Agent Chemotherapy | 52 |
| C. Standard of Care Control Arm | 56.5 |
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
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) |
|---|
| C. Standard of Care Control Arm | 0 | 31 |
,| E. Dual Agent Chemotherapy | 0 | 64 |
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
| Intervention | estimated percentage of participants (Number) |
|---|
| E. Dual Agent Chemotherapy | 46.1 |
| C. Standard of Care Control Arm | 46.6 |
Rate of Pathologic Complete Response in the Affected Breast After Protocol Therapy
The primary objective of this study is to define the rate of pathologic complete response rate (pCR) in the affected breast after the preoperative administration of NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with stage IIB-IIIC breast cancer. Pathologic complete response (pCR) is defined according to Hankoop et al [41] as either: the absence of any histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast or the presence of invasive tumor equal to or less than 10mm after preoperative treatment, determined at definitive breast surgery. (NCT00499122)
Timeframe: About 7 months
| Intervention | percentage of tumors (Median) |
|---|
| NOV-002 and Chemotherapy | 39 |
Definition of the Safety Profiles of Protocol Therapy
Definition of the safety profiles of protocol therapy in study participants as shown by the number of study participants experiencing adverse events or other toxicity. (NCT00499122)
Timeframe: Up to 30 days Post-Last Dose of Protocol Therapy, About 7 months
| Intervention | participants (Number) |
|---|
| NOV-002 and Chemotherapy | 41 |
Correlation Between Myeloid Derived Suppressor Cell (MDSC) Levels and Pathologic Complete Response (pCR) and Non-Responders
The investigators hypothesized that patients with favorable responses, i.e. pCR, are more likely to have significantly lower levels of MDSCs than non-responders. MDSC levels will be measured at baseline and on day 1 of each treatment cycle, cycles 1 through 8. (NCT00499122)
Timeframe: Baseline, Day 1 of Cycles 1 through 8, about 7 months
| Intervention | MDSC/uL (Mean) |
|---|
| Baseline, non-pCR | Baseline, pCR | Cycles 2-4 Day 1, non-pCR | Cycles 2-4 Day 1, pCR | Cycles 5-8 Day 1, non-pCR | Cycles 5-8 Day 1, pCR |
|---|
| NOV-002 and Chemotherapy | 257.4 | 124.3 | 534.2 | 207.8 | 363.7 | 171.5 |
Number of Participants Achieving Pathological Complete Response
Probability of response, defined as pathological complete remission based on tissue obtained at surgery. Pathological Complete Response (pCR): Patients without gross or microscopic evidence of residual disease at Radical Prostatectomy defined as pCR. (NCT00500110)
Timeframe: Every 3 months for 1 year, then every 6 months until disease progression or death
| Intervention | participants (Number) |
|---|
| Treatment | 0 |
Progression-Free Survival (PFS)
The time from the date of start of treatment until the first documented or confirmed disease progression, or death related to prostate cancer, whichever is earlier. (NCT00503984)
Timeframe: Up to 4.5 years
| Intervention | months (Median) |
|---|
| All Study Participants | 4.9 |
Overall Survival (OS)
The time from the date of initiation of study treatment until date of death from any cause. (NCT00503984)
Timeframe: Up to 4.5 years.
| Intervention | months (Median) |
|---|
| All Study Participants | 19.5 |
Number of Participants Experiencing Adverse Events After Beginning Protocol Therapy.
(NCT00503984)
Timeframe: Up to 4.5 years
| Intervention | participants (Number) |
|---|
| Level 1 - 75 Aza + 60 Doc | 3 |
| Level 2 - 75 Aza + 75 Doc | 4 |
| Level 3 - 100 Aza + 75 Doc | 3 |
| Level 4 - 150 Aza + 75 Doc | 12 |
Duration of Response
Length of time from the date of first observation of complete response (CR) or partial response (PR) to the date of first observation of disease progression, according to prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 1 (PCWG1) criteria. PSA response according to PCWG1 is defined as an least 50 percent decline in PSA level from baseline that was maintained for at least three weeks. (NCT00503984)
Timeframe: Up to 4.5 years.
| Intervention | weeks (Median) |
|---|
| All Study Participants Achieving PSA Response | 20.5 |
Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Azacitidine and Docetaxel)
Determination of a safe and potentially efficacious phase II dose of azacitidine in combination with docetaxel and prednisone that can be used for the treatment of hormone refractory metastatic prostate cancer. (NCT00503984)
Timeframe: Up to 1.5 years
| Intervention | mg/m2 (Number) |
|---|
| Initial RPTD Azacitidine (mg/m2) | Initial RPTD Docetaxel (mg/m2) | Reduced RPTD Azacitidine (mg/m2) | Reduced RPTD Docetaxel (mg/m2) |
|---|
| Phase 1 - Aza + Doc | 150 | 75 | 75 | 75 |
Phase I - Recommended Phase Two Dose (RPTD) of Azacitidine and Docetaxel in Combination With Prednisone. (Prednisone)
Determination of a safe and potentially efficacious phase II dose of azacitidine in combination with docetaxel and prednisone that can be used for the treatment of hormone refractory metastatic prostate cancer. (NCT00503984)
Timeframe: Up to 1.5 years
| Intervention | mg (Number) |
|---|
| Initial RPTD Prednisone (mg) | Reduced RPTD Prednisone (mg) |
|---|
| Phase 1 - Aza + Doc | 5 | 5 |
Number of Participants Achieving Prostate-specific Antigen (PSA) Response.
Number of participants achieving prostate-specific antigen (PSA) response according to Prostate Cancer Working Group 1 (PCWG1) criteria. PSA response according to PCWG1 is defined as an least 50 percent decline in PSA level from baseline that was maintained for at least three weeks. (NCT00503984)
Timeframe: Up to 4.5 years.
| Intervention | participants (Number) |
|---|
| Phase 1: Level 1 - 75 Aza + 60 Doc | 0 |
| Phase 1: Level 2 - 75 Aza + 75 Doc | 1 |
| Phase 1: Level 3 - 100 Aza + 75 Doc | 2 |
| Phase 1: Level 4 - 150 Aza + 75 Doc | 4 |
| Phase 2 - Aza + Doc Initial RPTD | 3 |
| Phase 2 - Aza + Doc Reduced RPTD | 0 |
Number of Participants Achieving Complete Response (CR) or Partial Response (CR) to Protocol Therapy.
"Number of participants achieving Complete Response (CR) or Partial Response to protocol therapy according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 Criteria. Per RECIST 1.0 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; " (NCT00503984)
Timeframe: Up to 4.5 years
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) |
|---|
| Phase 1: Level 1 - 75 Aza + 60 Doc | 0 | 0 |
,| Phase 1: Level 3 - 100 Aza + 75 Doc | 1 | 0 |
,| Phase 1: Level 4 - 150 Aza + 75 Doc | 0 | 1 |
,| Phase 2 - Aza + Doc Initial RPTD | 0 | 1 |
Overall Response Rate (RR)
Overall Response: Complete Response (CR) + Partial Response (PR). To determine the response rate (RR) of the investigational treatment regimen. Response and progression were evaluated in the study by using the Gynecologic Oncology Group (GOG) Response Evaluation Criteria in Solid Tumors (RECIST) method or modified Rustin Criteria for CA-125 measurements. (NCT00504257)
Timeframe: Up to 5 years
| Intervention | participants (Number) |
|---|
| Avastin and Docetaxel | 22 |
Occurrence of Grade 3 or 4 Toxicity
Number of participants with Grade 3 or 4 Toxicity based on 278 treatment cycles. Toxicity was graded per the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. (NCT00504257)
Timeframe: Up to 4 years
| Intervention | participants (Number) |
|---|
| Avastin and Docetaxel | 27 |
Six Month Progression Free Survival (PFS)
"Percentage of participants with PFS at six months. PFS: Period from study entry until disease progression, death due to disease progression, or date of last contact.~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, progression of non-target lesions, or the appearance of one or more new lesions." (NCT00504257)
Timeframe: 6 months per participant
| Intervention | percentage of participants (Number) |
|---|
| Avastin and Docetaxel | 43.9 |
Overall Survival (OS)
Overall Survival (OS): defined as observed length of life from entry onto the protocol to death, or for living patients, date of last contact (regardless of whether or not this contact is on a subsequent protocol). Survival (PFS and OS) were analyzed using the Kaplan-Meier method with standard errors based on Greenwood's formula. (NCT00504257)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Avastin and Docetaxel | 12.4 |
1-year Progression Free Survival Rate in Chemo-naive Select Stage IIIB or Stage IV NSCLC Patients
One-year progression-free survival was defined from the time from initiation of study treatment to the first date of disease progression or death as a result of any cause. Progression was 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. Time was censored at the date of the last follow-up visit for patients who were still alive and have not progressed. The one-year progression free survival rate is a percentage, representing the fraction of treated patients who, after one-year, are disease free or alive. (NCT00509366)
Timeframe: 1 year
| Intervention | percentage of treated patients (Number) |
|---|
| Treatment | 19.15 |
Mean Change From Baseline to Follow-up Cycle in Quality of Life - Functional Assessment of Cancer Therapy-Lung (FACT-L)
The outcome measure is mean change in the Trial Outcome Index (TOI) between baseline and each follow-up assessment measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L). The FACT-L instrument consists of 34 items to assess physical (PWB), social and family (SWB), emotional (EWB), functional well-being (FWB) and additional lung specific concerns (LCS). Using a 5-point Likert type scale, responses to individual items range from 0 (not at all) to 4 (Very Much) with higher scores indicating better quality of life. The TOI is the sum of PWB (7 items), FWB (7 items) and LCS scores (7 items), which each have a possible range between 0 and 28. Therefore, TOI ranges from 0 to 84. (NCT00509366)
Timeframe: Baseline, Every 21 days for a maximum of 6 cycles
| Intervention | units on a scale (Mean) |
|---|
| Change from baseline to Cycle 1 | Change from baseline to Cycle 2 | Change from baseline to Cycle 3 | Change from baseline to Cycle 4 | Change from baseline to Cycle 5 | Change from baseline to Cycle 6 |
|---|
| Treatment | 0.15 | -1.04 | -1.28 | -2.62 | -6.14 | -0.72 |
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)
| Intervention | participants (Number) |
|---|
| Second-Line: EP, Course 1 | 43 |
| Second-Line: EP, Course 2 | 24 |
Change From Baseline in Erectile Function Domain of International Index of Erectile Function (EF-IIEF) Total Score at EOT
EF-IIEF is a 6-item erectile function domain of IIEF. It consists of Question 1, 2, 3, 4, 5, and 15 of IIEF questionnaire. 5 questions are scored from 0 (no activity) to 5 (very high activity) and 1 question is scored from 1 (very low activity) to 5 (very high activity). Total EF-IIEF score ranges from 1 to 30, where higher score indicates high activity. (NCT00514917)
Timeframe: Baseline, EOT (up to Month 18)
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=201, 205) | Change at EOT (n=180, 186) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 6.4 | -3.1 |
,| Leuprolide+Bicalutamide | 6.8 | -3.3 |
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Trial Outcome Index (TOI) Score at EOT
Physical well-being, functional well-being, and prostate cancer concerns sub-scales of the FACT-P questionnaire were combined to calculate TOI. Total TOI score ranges from 0 to 104, with higher scores representing a better quality of life with fewer symptoms. (NCT00514917)
Timeframe: Baseline, EOT (up to Month 18)
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=206, 206) | Change at EOT (n=187, 187) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 82.1 | -5.4 |
,| Leuprolide+Bicalutamide | 80.4 | -3.1 |
Change From Baseline in Multidimensional Assessment of Fatigue (MAF) Index Score at EOT
MAF scale consists of 16-items to measure 4 dimensions of fatigue during past week: severity (Item 1-2), distress (Item 3), degree of interference in activities of daily living (Item 4-14), and timing (Item 15-16). Item 1-14 are scored on a numeric rating scale from 1 to 10, where higher score indicate more severity/distress/interference. Item 15-16 had multiple choice responses (4 responses each). Scale Index was calculated using Item 1-15, in following steps: 1) Item 15 score converted to 1-10 scale by multiplying the score with 2.5; 2) Average score was calculated from Item 4-14; 3) Finally scale index was calculated by adding Items 1, 2, 3 scores with average score from step 2 and converted score of Item 15 from step 1. Total MAF scale index score ranges 1 (no fatigue) to 50 (severe fatigue). (NCT00514917)
Timeframe: Baseline, EOT (up to Month 18)
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=168, 171) | Change at EOT (n=127, 144) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 16.4 | 4.0 |
,| Leuprolide+Bicalutamide | 16.6 | 2.6 |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
TEAE: any adverse event (AE) that occurred or worsened during the on-treatment period, which was the period from first administration of study treatment until 30 days after last administration of study treatment. AE: any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious AE: 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, or medically important. Drug-related AEs were any untoward medical occurrences attributed to study drug in a participant who received study drug. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 Grade 3 (severe) and Grade 4 (life threatening/disabling) TEAEs were also reported. (NCT00514917)
Timeframe: From first administration of study treatment until 30 days after the last administration of study treatment
| Intervention | participants (Number) |
|---|
| Any TEAE | Any Serious AE | Any TEAE Resulting in Death | Any TEAE Leading to any Treatment Discontinuation | Any Grade 3-4 TEAE | Docetaxel Related TEAE | Leuprolide Related TEAE | Bicalutamide Related TEAE | Any Treatment Related TEAE | Any Grade 3-4 Serious TEAE | Any TEAE Leading to Interruption of any Treatment |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 188 | 49 | 0 | 35 | 94 | 183 | 109 | 52 | 184 | 43 | 77 |
,| Leuprolide+Bicalutamide | 163 | 20 | 1 | 1 | 22 | NA | 136 | 74 | 136 | 14 | 1 |
Progression-Free Survival (PFS) Rate at Month 36 in Testosterone Specific Evaluable Population
PFS rate at Month 36 was defined as probability of being progression-free at Month 36. PFS rate was estimated using the Kaplan-Meier method. (NCT00514917)
Timeframe: Month 36
| Intervention | percent chance of being progression-free (Number) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 15.8 |
| Leuprolide+Bicalutamide | 9.1 |
Cancer-Specific Survival: Number of Participants Who Died (Cancer-Specific)
The cancer-specific survival was the time from the date of randomization to the date of death due to prostate cancer. Cancer-specific survival was to be analyzed using the Kaplan-Meier method. However, the analysis was not performed due to insufficient number of events. Reported is the number of participants who died from prostate cancer. (NCT00514917)
Timeframe: Randomization until death due to prostate cancer, assessed up to Month 60
| Intervention | participants (Number) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 2 |
| Leuprolide+Bicalutamide | 3 |
Progression-Free Survival (PFS) Rate at Month 36 in ITT Population
PFS rate at Month 36 was defined as probability of being progression-free at Month 36. PFS rate was estimated using the Kaplan-Meier method. (NCT00514917)
Timeframe: Month 36
| Intervention | percent chance of being progression-free (Number) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 15.5 |
| Leuprolide+Bicalutamide | 8.6 |
Overall Survival (OS): Number of Participants Who Died (All Cause)
The OS was the time interval from the date of randomization to the date of death due to any cause. OS was to be analyzed using the Kaplan-Meier method. However, the analysis was not performed due to insufficient number of events. Reported is the number of participants who died from any cause. (NCT00514917)
Timeframe: Randomization until death due to any cause, assessed up to Month 60
| Intervention | participants (Number) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 4 |
| Leuprolide+Bicalutamide | 11 |
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) Total Score at End of Treatment (EOT)
FACT-P is a 39-item participant questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better quality of life with fewer symptoms. A score of 156 represents the best outcome. (NCT00514917)
Timeframe: Baseline, EOT (up to Month 18)
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=206, 205) | Change at EOT (n=186, 184) |
|---|
| Docetaxel+Leuprolide+Bicalutamide | 121.4 | -4.9 |
,| Leuprolide+Bicalutamide | 119.6 | -3.4 |
6 Month Progression Free Survival (PFS)
"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, or similar definition as accurate and appropriate" (NCT00515411)
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 6 months
| Intervention | percentage of paticipants (Mean) |
|---|
| Arm A, - Modified DCF | 63 |
| ARM B - Parent DCF With G-CSF | 53 |
| Arm C - Modified DCF+ Trastuzumab | 73 |
Overall Survival
Overall survival measured in months (NCT00515411)
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 43 months
| Intervention | months (Median) |
|---|
| Arm A, - Modified DCF | 18.8 |
| ARM B - Parent DCF With G-CSF | 12.6 |
| Arm C - Modified DCF+ Trastuzumab | 24.9 |
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. (NCT00517829)
Timeframe: Treatment will continue until disease progression or intolerable toxicity
| Intervention | months (Median) |
|---|
| DOCOX | 8.5 |
| DOCOX+Cebuximab | 9.4 |
Progression-free Survival
"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." (NCT00517829)
Timeframe: Treatment will continue until disease progression or intolerable toxicity, up to 2 years
| Intervention | months (Median) |
|---|
| DOCOX | 4.7 |
| DOCOX+Cebuximab | 5.1 |
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. (NCT00517829)
Timeframe: Treatment will continue until disease progression or intolerable toxicity
| Intervention | months (Median) |
|---|
| DOCOX | 1.3 |
| DOCOX+Cebuximab | 1.4 |
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. (NCT00517829)
Timeframe: Treatment will continue until disease progression or intolerable toxicity
| Intervention | months (Median) |
|---|
| DOCOX | 7.3 |
| DOCOX+Cebuximab | 5.6 |
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. (NCT00517829)
Timeframe: Treatment will continue until disease progression or intolerable toxicity.
| Intervention | percentage of participants (Number) |
|---|
| DOCOX | 26.5 |
| DOCOX+Cebuximab | 38.0 |
Prostate Specific Antigen Response Rate
Prostate specific antigen (PSA) response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed at least 3 weeks later. Increases of any magnitude during the first 12 weeks were ignored in determining PSA response. (NCT00519285)
Timeframe: Before randomization (baseline) then every 3 weeks up to PSA progression (≥25% increase) or the cut-off date, whichever occurred first
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 63.5 |
| Aflibercept | 68.6 |
Tumor Response Rate in Participants With Measurable Disease
Tumor response was defined as either a Complete Response (disappearance of all target lesions) or a Partial Response (≥30% decrease from baseline in target lesions) as assessed by Response Evaluation Criteria In Solid Tumors (RECIST)version 1.0. (NCT00519285)
Timeframe: Before randomization (baseline) then every 3 months up to tumor progression (≥25% increase) or the cut-off date, whichever occurred first
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 28.1 |
| Aflibercept | 38.7 |
Number of Participants With Adverse Events as a Measure of Safety
"Adverse Events (AE) are any unfavorable and unintended sign, symptom, syndrome or illness observed by the investigator or reported by the participant during the study.~AE were collected at regular intervals throughout the study then graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.3.0)." (NCT00519285)
Timeframe: From first dose of study treatment (aflibercept/placebo or docetaxel whichever came first) to last dose of study treatment (aflibercept/placebo or docetaxel whichever came last) + 30 days
| Intervention | participants (Number) |
|---|
| Any Adverse Event | - Grade 3-4 AE | - Serious AE | - AE leading to death | --- Related AE leading to death | - AE leading to permanent discontinuation | - AE leading to premature discontinuation |
|---|
| Aflibercept | 607 | 470 | 331 | 46 | 19 | 268 | 116 |
,| Placebo | 585 | 290 | 184 | 23 | 8 | 125 | 73 |
Number of Participants With Positive Anti-aflibercept Antibody Levels as a Measure of Immunogenicity of Aflibercept
"Serum for detection of anti-drug antibodies (ADA) was collected in patients treated in selected centers only. Samples were analyzed using a titer-based, bridging immunoassay developed and validated to detect ADAs in human serum.~Samples with positive antibody levels were further analyzed using a validated, non-quantitative ligand binding assay to detect neutralizing antibodies Ab).~A participant was considered to have positive antibody levels if antibodies were detected above the quantification limits." (NCT00519285)
Timeframe: Pre-dose of cycle 1 (baseline), pre-dose of each every other cycle, then 30 and 90 days after the last administration of the study drug
| Intervention | participants (Number) |
|---|
| At baseline | At any time post-baseline | - Neutralizing Ab | - Not neutralizing Ab | - Neutralizing potential not evaluated |
|---|
| Aflibercept | 2 | 9 | 2 | 5 | 2 |
,| Placebo | 0 | 4 | 0 | 2 | 2 |
Overall Survival Time
"Overall survival (OS) time was measured as the time from date of randomization to the date of death due to any cause.~The median OS time and its 95.6% confidence interval were estimated using the Kaplan-Meier method. In the absence of confirmation of death, the participant was censored at the last date he/she was known to be alive or the study cut-off date (when 873 deaths have occurred), whichever was earlier." (NCT00519285)
Timeframe: From randomization up to the cut-off date (median follow-up of 35.4 months)
| Intervention | months (Median) |
|---|
| Placebo | 21.22 |
| Aflibercept | 22.14 |
Pain Progression-free Survival Time
"Pain progression was defined as either ≥1-point increase in Present Pain Intensity (PPI) score or ≥25% increase in Analgesics Score (AS) confirmed at least 3 weeks later, or requirement for palliative radiotherapy. PPI scale is a self-report 0-5 scale to assess pain intensity - a score 0 reflects no pain, a score 5 reflects excruciating pain. AS is a scoring method to assess analgesics consumption. Each analgesic is scored 1 or 4 depending on the analgesic type and dose. AS is the sum of the analgesic scores.~Pain progression-free survival (PFS) time was measured as the time from the date of randomization up to the date of first pain progression or death due to any cause, whichever occurred first.~The median pain-PFS and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of event, the participant was censored at the the date of last assessment without evidence of pain progression or the study cut-off date, whichever was earlier." (NCT00519285)
Timeframe: From randomization up to the cut-off date (median follow-up of 35.4 months)
| Intervention | months (Median) |
|---|
| Placebo | 9.72 |
| Aflibercept | 9.20 |
Pain Response Rate
Pain response was defined as either a ≥2-point decrease from baseline in Present Pain Intensity (PPI) score without increase in Analgesics Score (AS), or a ≥50% decrease from baseline in AS without increase in the PPI score confirmed at least 3 weeks later. Increases in PPI or AS during the first 12 weeks were ignored in determining pain response. (NCT00519285)
Timeframe: Before randomization (baseline) then every 3 weeks up to pain progression or the cut-off date, whichever occurred first
| Intervention | percentage of participants (Number) |
|---|
| Placebo | 46.3 |
| Aflibercept | 35.8 |
Progression Free Survival Time
"Disease progression was defined as a composite of: Radiological tumor progression (≥20% increase in target lesions, or appearance of at least 2 new bone lesions); PSA progression (≥25% increase in PSA level confirmed 3 weeks later); Pain progression (increase in pain intensity or in analgesic consumption for cancer related pain confirmed 3 weeks later); Radiotherapy for cancer related symptoms; Occurence of Skeletal related events (SRE).~Progression Free survival (PFS) time was measured as the time from the date of randomization up to the date of occurrence of the first event defining a disease progression or death due to any cause, whichever occurred first.~The median PFS time and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of disease progression, the participant was censored at the the date of last assessment without evidence of progression or the study cut-off date, whichever was earlier." (NCT00519285)
Timeframe: From randomization up to the cut-off date (median follow-up of 35.4 months)
| Intervention | months (Median) |
|---|
| Placebo | 6.24 |
| Aflibercept | 6.90 |
Prostate Specific Antigen Progression-free Survival Time
"Prostate specific antigen (PSA) progression was defined as ≥25% increase in PSA level confirmed 3 weeks later, above the nadir in participants who had achieved a PSA response, or above the baseline in participants who hadn't achieved a PSA response.~PSA progression-free survival (PFS) time was defined as the time from the date of randomization up to the date of the first documented PSA progression or death due to any cause, whichever occurred first.~The median PSA-PFS time and its 95% confidence interval were estimated using the Kaplan-Meier method. In the absence of PSA progression or death, the participant was censored at the the date of last assessment without evidence of progression or the study cut-off date, whichever was earlier." (NCT00519285)
Timeframe: From randomization up to the cut-off date (median follow-up of 35.4 months)
| Intervention | months (Median) |
|---|
| Placebo | 8.11 |
| Aflibercept | 8.25 |
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).
| Intervention | percentage of participants (Number) |
|---|
| Tumor Response Rate | Disease Control Rate | Complete Response | Partial Response | Stable Disease | Progressive Disease | Unknown |
|---|
| Docetaxel Plus Carboplatin | 23.1 | 64.4 | 0 | 23.1 | 41.3 | 17.3 | 18.3 |
,| Pemetrexed Plus Carboplatin | 34.0 | 74.5 | 0.9 | 33.0 | 40.6 | 16.0 | 9.4 |
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).
| Intervention | months (Median) |
|---|
| Pemetrexed Plus Carboplatin | 3.2 |
| Docetaxel Plus Carboplatin | 0.7 |
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).
| Intervention | participants (Number) |
|---|
| Non-Serious Adverse Events (AEs) | Serious Adverse Events (SAEs) |
|---|
| Docetaxel Plus Carboplatin | 100 | 35 |
,| Pemetrexed Plus Carboplatin | 94 | 28 |
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).
| Intervention | participants (Median) |
|---|
| Pemetrexed Plus Carboplatin | 12.2 |
| Docetaxel Plus Carboplatin | 2.0 |
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).
| Intervention | months (Median) |
|---|
| Pemetrexed Plus Carboplatin | 3.6 |
| Docetaxel Plus Carboplatin | 1.3 |
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).
| Intervention | months (Median) |
|---|
| Pemetrexed Plus Carboplatin | 5.8 |
| Docetaxel Plus Carboplatin | 6.0 |
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).
| Intervention | months (Median) |
|---|
| Pemetrexed Plus Carboplatin | 14.9 |
| Docetaxel Plus Carboplatin | 14.7 |
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).
| Intervention | months (Median) |
|---|
| Pemetrexed Plus Carboplatin | 5.5 |
| Docetaxel Plus Carboplatin | 5.4 |
Time to Progression
Estimated probable duration from on-study date to date of disease progression, using the Kaplan-Meier method with censoring (see analysis population description for additional details). Disease progression is defined under RECIST v1.1 as >=20% increase in sum of longest diameters of target lesions, unequivocal progression of non-target lesions, or appearance of new lesions. (NCT00520845)
Timeframe: 2 years from date of registration
| Intervention | days (Median) |
|---|
| Treatment Arm | 89 |
Overall Response Rate
Overall response rate is measured by complete response + partial response. 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. Patients are categorized according to the best response achieved prior to occurrence of progressive disease, where best response hierarchy is CR>PR>SD>PD. (NCT00520845)
Timeframe: On-treatment date to date of disease progression (assessed at 6 weeks up to 2 years)
| Intervention | participants (Number) |
|---|
| Treatment Arm | 0 |
Progression Free Survival
Progression Free Survival (PFS) defined as the time from the first study drug administration until the first day of radiological and/or symptomatic disease progression is documented, or the start of further anticancer therapy or death from any cause, whichever occurs first. Kaplan-Meier curve was used to estimate PFS. 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 lesion. (NCT00526110)
Timeframe: Assessed from baseline to 30 months
| Intervention | months (Median) |
|---|
| Phase II | 6.5 |
Maximum Tolerated Dose (MTD)
MTD is the highest dose at which 1 or fewer dose limiting toxicities (DLT's) are observed in 6 patients. DLT defined as any non-hematologic grade III/IV or neutropenia-associated (infection or fever treated in the hospital) toxicity attributable to this therapy. Response evaluated after two 14-day treatments of Docetaxel, 5-Fluorouracil and Oxaliplatin (One cycle = 28 days). (NCT00526110)
Timeframe: 28 days
| Intervention | mg/m^2 (Number) |
|---|
| Phase I | 50 |
Prostate-specific Antigen (PSA) Response in Accordance With the Prostate Specific Antigen Working Group
PSA < 4.0 ng/ml. is a CR. A 50% decline or better in PSA is a PR. Less than a 50% decline in PSA and less than a 25% increase in PSA is SD. A 25% or greater increase in PSA level by at least 5 ng/mL is PD by PSA only. The point estimate and 95% Wilson CI estimates of the proportion for the Prostate-specific antigen (PSA) response will be computed . (NCT00527124)
Timeframe: Up to 52 weeks
| Intervention | proportion of evaluable patients (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Arm I | .35 | .27 | .35 | .04 |
,| Arm II | .12 | .54 | .31 | .04 |
Overall Response Rate Evaluated by the RECIST Criteria
"The overall response is determined by combining the patient's status on target lesions, PSA, non-target lesions, and new disease as defined in the following table.~Target Lesions CR CR PR SD PD Any Any Any~PSA Response CR PR PR Non-PD Any Any PD Any~Non-Target Lesions CR Non-CR/Non-PD Non-PD Non-PD Any PD Any Any~New Lesions No No No No Yes or No Yes or No Yes or No Yes~Overall Response CR PR PR SD PD PD PD PD" (NCT00527124)
Timeframe: Up to 52 weeks
| Intervention | proportion of evaluable patients (Number) |
|---|
| SD | PD |
|---|
| Arm I | .92 | .08 |
,| Arm II | .92 | .08 |
Time to Progression
Analyzed with standard K-M methodology. Both point and 95% CI estimates of the median and other statistics (e.g., the 3-month rate, 6-month rate, etc.) will be computed from the censored distribution of TTP. These point and CI estimates will be reported for all patients combined, and separately for each treatment arm. (NCT00527124)
Timeframe: The time from registration date until documented clinical disease progression, or until date of death, whichever occurs first, assessed up to 52 weeks
| Intervention | months (Median) |
|---|
| Arm I | 8.0 |
| Arm II | 6.4 |
Overall Survival
Analyzed with standard K-M methodology. A 12 month survival rate will be calculated since median survival was not reached by the end of the study period. (NCT00527124)
Timeframe: The time from registration date until death from any cause, assessed up to 52 weeks
| Intervention | percentage of patients (Number) |
|---|
| Arm I | 71 |
| Arm II | 76 |
6-month Progression-free Survival (PFS) Proportion
The proportion of patients on each treatment arm who survive ≥ 6.00 months progression-free (NCT00527124)
Timeframe: Followed for 52 weeks at 3 month intervals after coming off treatment, time period equal to the length of treatment + up to 12 months
| Intervention | percentage of patients (Number) |
|---|
| Arm I | 60 |
| Arm II | 54 |
Local-regional Progression (3 Year Rate)
Time from registration to date of local progression (failure), death (competing risk), or last follow-up (censored). Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method. (NCT00528866)
Timeframe: Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 0 |
"Number of Patients With Acute Adverse Events (Based on CTCAE, v3.0)"
The number of patients with at least one grade 3 or higher adverse event (AE) from start of treatment to 90 days after the planned end of treatment (21 days after last docetaxel dose). 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. (NCT00528866)
Timeframe: From start of treatment to 90 days after the planned end of treatment (21 days after last docetaxel dose). Analysis occurs at the time of the primary analysis. (Patients are followed until death or study termination whichever occurs first.
| Intervention | participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 57 |
"Time to Late Grade 3+ Adverse Events (Based on CTCAE, v3.0)"
Two-year rate shown (cumulative incidence method). Adverse events are graded using CTCAE v3.0. Time of first late adverse event occurrence of the Grade 3+ adverse event between 91 days and 730 days from the completion of treatment (3 weeks after the last planned docetaxel dose) calculated. 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. (NCT00528866)
Timeframe: From 91 to 730 days after the planned end of treatment (21 days after last docetaxel dose). Analysis occurs at the time of the primary analysis. (Patients are followed from registration to death or study termination whichever occurs first.)
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 8.1 |
Time to Biochemical (PSA) Failure (3-year Rate)
Failure is defined as PSA ≥ 0.4 ng/mL confirmed by a second higher PSA or initiation of non-protocol hormones. Death is considered a competing risk. Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method. (NCT00528866)
Timeframe: Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 25.7 |
Prostate Cancer Death (3-year Rate)
Time from registration to date of distant metastasis (failure), death (competing risk), or last follow-up (censored). Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method. (NCT00528866)
Timeframe: Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 0 |
Overall Survival (3-year Rate)
Time from registration to date of death (failure) or last follow-up (censored). Three-year rate and 95% confidence interval were estimated by the Kaplan-Meier method. (NCT00528866)
Timeframe: Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 98.6 |
Number of Participants Free From Progression at 3 Years
Failure was defined as PSA ≥ 0.4 ng/mL after the end of radiation therapy confirmed by a second higher PSA, non-protocol hormones, local-regional progression, distant metastasis, or death, within 3 years after study registration. Freedom from progression (FFP) rate under null hypothesis was 50%; under alternative hypothesis ≥ 70%. Per Fleming's multiple testing procedure with 3 stages, 69 patients (76 allowing for 10% ineligible) were required for 90% power and type I error 0.025. If ≥ 44 of 69 patients had a FFP event, we would reject 50% FFP rate in favor of ≥ 70%. Analysis was out of 74 patients (not 69), so ≥ 44 was revised to ≥ 46. (NCT00528866)
Timeframe: From registration to 3 years.
| Intervention | participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 54 |
Non-prostate Cancer Death (3-year Rate)
Time from registration to date of death due to other causes (failure), death due to prostate cancer (competing risk), or last follow-up (censored).Three-year failure rate and 95% confidence interval were estimated by the cumulative incidence method. (NCT00528866)
Timeframe: Analysis occurs after all patients have been on study for at least 3 years. (Patients are followed from registration to death or study termination whichever occurs first.)
| Intervention | percentage of participants (Number) |
|---|
| Androgen Suppression + RT + Docetaxel | 1.4 |
Overall Survival (OS)
"OS was time interval from the date of randomization to the date of death due to any cause. If death was not observed during the study, overall survival time was censored at the last date the participant was known to be alive, or the study cutoff date, whichever was earlier. The cut-off date for the OS was date when 687 deaths were observed.~OS was estimated from Kaplan-Meier Curves." (NCT00532155)
Timeframe: Baseline to the date when 687 deaths occurred (26 January 2011)
| Intervention | months (Median) |
|---|
| Placebo/Docetaxel | 10.41 |
| Aflibercept/Docetaxel | 10.05 |
Progression Free Survival (PFS)
"PFS was defined as the time interval between the date of randomization and the time of occurrence of the first radiological tumor progression detected by a computer tomography (CT) scan and /or by Magnetic Resonance Imaging (MRI); or death due to any cause; whichever was earlier. Participants without disease progression were censored at the earliest date between their last valid tumour assessment and the data cutoff date.~PFS was estimated from Kaplan-Meier Curves." (NCT00532155)
Timeframe: Baseline to data cut-off (26 January 2011)
| Intervention | months (Median) |
|---|
| Placebo/Docetaxel | 4.11 |
| Aflibercept/Docetaxel | 5.19 |
Overall Response (OR) Rate as Per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria
"Participants with OR were those who had a confirmed complete response [CR] or a confirmed partial response [PR], based on RECIST criteria, in which~CR refected the disappearance of all tumor lesions (with no new tumors)~PR reflected a pre-defined decrease in tumor burden - a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD~OR was CR + PR The response rate was the percent of participants with a response.~To determine a response, tumors were assessed by the investigators using Computerized Tomography (CT) scans or Magnetic Resonance Imaging (MRI) scans; and an observed response was confirmed by repeated imaging after 4 - 6 weeks." (NCT00532155)
Timeframe: Baseline to data cut-off (26 January 2011)
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) rate | Partial Response (PR) rate | Overall Response (OR) rate |
|---|
| Aflibercept/Docetaxel | 0.2 | 23.0 | 38.6 |
,| Placebo/Docetaxel | 0.2 | 8.6 | 8.9 |
16 Weeks Progression-free Survival
To determine the rate of progression-free survival (PFS) at 16 weeks for the combination therapy of erlotinib and docetaxel for subjects in the Biliary stratum, per RECIST criteria. Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions taking as reference the smallest sum recorded since the treatment started or the appearance of one or more new lesions. (NCT00532441)
Timeframe: Start of treatment until disease progression per RECIST criteria up to 16 weeks
| Intervention | months (Median) |
|---|
| Biliary | 4.7 |
| Hepatocellular | 3.5 |
Response Rate
Determine the Response Rate Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) (NCT00532441)
Timeframe: 18 months
| Intervention | participants (Number) |
|---|
| Complete Response or Partial Response | Stable Disease | Progressive Disease |
|---|
| Erlotinib and Docetaxel: Biliary | 0 | 7 | 4 |
,| Erlotinib and Docetaxel: Hepatocellular | 0 | 6 | 7 |
Overall Survival
Determine Overall Survival (NCT00532441)
Timeframe: 18 Months
| Intervention | months (Median) |
|---|
| Hepatocellular | 6.7 |
| Biliary | 5.7 |
Number of Patients With Adverse Event (AE)
(NCT00536107)
Timeframe: From time consent was given to 28 days after last dose of study drug.
| Intervention | Participants (Number) |
|---|
| Gefitinib | 8 |
| Docetaxel | 6 |
Number of Patients With Serious Adverse Events (SAEs)
(NCT00536107)
Timeframe: From time consent was given to 28 days after last dose
| Intervention | participants (Number) |
|---|
| Gefitinib | 2 |
| Docetaxel | 1 |
Percent Change From Baseline in 'Vascular Endothelial Growth Factor (VEGF)' Marker Concentration
Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. (NCT00537381)
Timeframe: Baseline, Week 6, 7, 10 and 13
| Intervention | Percent change (Mean) |
|---|
| Percent Change at Week 6 (n = 10, 48) | Percent Change at Week 7 (n = 10, 54) | Percent Change at Week 10 (n = 11, 51) | Percent Change at Week 13 (n = 11, 41) |
|---|
| Docetaxel + Prednisone + Intetumumab | -9.64 | 11.69 | 32.11 | 20.19 |
,| Docetaxel + Prednisone + Placebo | -10.00 | -3.10 | 3.96 | 8.22 |
Number of Participants With Best Overall Response (OR)
Number of participants with best OR is based on assessment of confirmed complete response (CR) or confirmed partial response (PR). Confirmed CR is defined as disappearance of all target lesions. Confirmed PR is defined as greater than or equal to 30 percent decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD. Confirmed responses are those that persist on repeat imaging study greater than or equal to 4 weeks after initial documentation of response. (NCT00537381)
Timeframe: Baseline up to 6 months after last dose of study treatment, assessed up to 551 days
| Intervention | Participants (Number) |
|---|
| Complete Response | Partial Response |
|---|
| Docetaxel + Prednisone + Intetumumab | 0 | 8 |
,| Docetaxel + Prednisone + Placebo | 1 | 9 |
Percent Change From Baseline in 'C-telopeptide of Type I Collagen (CTx)' Marker Concentration
Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. (NCT00537381)
Timeframe: Baseline, Week 6, 7, 10 and 13
| Intervention | Percent change (Mean) |
|---|
| Percent Change at Week 6 (n = 10, 48) | Percent Change at Week 7 (n = 10, 54) | Percent Change at Week 10 (n = 11, 51) | Percent Change at Week 13 (n = 11, 41) |
|---|
| Docetaxel + Prednisone + Intetumumab | -30.81 | -39.78 | -25.48 | -44.89 |
,| Docetaxel + Prednisone + Placebo | 1.45 | -11.58 | 2.39 | 5.22 |
Number of Participants With Prostate Specific Antigen (PSA) Response
The PSA response is defined as at least a 50 percent decrease in PSA below the baseline value, confirmed by a second PSA value greater than or equal to 6 weeks later. A participant was considered to be a PSA responder if and only if the response occurs prior to PSA progression (increase of at least 25 percent and an increase of 5 nanogram per milliliter from the lowest observed PSA value since initiation of treatment, to be confirmed greater than or equal to 3 weeks later). (NCT00537381)
Timeframe: Baseline up to 6 months after last dose of study treatment or early withdrawal, assessed up to 601 days
| Intervention | Participants (Number) |
|---|
| Docetaxel + Prednisone + Placebo | 43 |
| Docetaxel + Prednisone + Intetumumab | 27 |
Overall Survival
Overall Survival is defined as the time from the date of randomization to death due to any cause. For participants who were alive at the time of analysis, overall survival was censored at the last contact date. (NCT00537381)
Timeframe: Baseline until death (up to 887 days)
| Intervention | Days (Median) |
|---|
| Docetaxel + Prednisone + Placebo | 626.0 |
| Docetaxel + Prednisone + Intetumumab | 522.0 |
Progression-Free Survival (PFS)
The PFS was assessed as median number of days from baseline until the first documented sign of disease progression (increase in disease; radiographic, clinical, or both) or death due to any cause, whichever occurred earlier. (NCT00537381)
Timeframe: Baseline up to 6 months after last dose of study treatment, assessed up to 551 days
| Intervention | Days (Median) |
|---|
| Docetaxel + Prednisone + Placebo | 336.0 |
| Docetaxel + Prednisone + Intetumumab | 232.0 |
Percent Change From Baseline in 'N-telopeptide of Type I Collagen (NTx)' Marker Concentration
Percent change = marker concentration at time of measurement minus baseline value divided by baseline value multiplied by 100. (NCT00537381)
Timeframe: Baseline, Week 6, 7, 10 and 13
| Intervention | Percent change (Mean) |
|---|
| Percent Change at Week 6 (n = 10, 48) | Percent Change at Week 7 (n = 10, 54) | Percent Change at Week 10 (n = 11, 51) | Percent Change at Week 13 (n = 11, 40) |
|---|
| Docetaxel + Prednisone + Intetumumab | -21.37 | -23.44 | -21.71 | -36.47 |
,| Docetaxel + Prednisone + Placebo | -0.77 | 1.58 | 2.55 | -3.87 |
Response Rate
(NCT00541099)
Timeframe: Every 8 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Avastin & Docetaxel | 0 |
Survival
(NCT00541099)
Timeframe: 6 months when treated with combination of Avastin and weekly docetaxel
| Intervention | percentage of participants surviving (Number) |
|---|
| Avastin & Docetaxel | 75 |
Overall Survival
Overall survival using Kaplan-Meier method. (NCT00541099)
Timeframe: 4 weeks after removal from study or until death
| Intervention | months (Median) |
|---|
| Avastin & Docetaxel | 35.7 |
Toxicity According to NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
Toxicity: using the highest grade of each toxicity experienced by each patient according to NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. (NCT00541099)
Timeframe: 1st and 2nd week of each 21 day cycle, up to six cycles.
| Intervention | Adverse event (Number) |
|---|
| Serious (grade 3 or 4) | other (grade 0, 1, or 2) |
|---|
| Avastin & Docetaxel | 21 | 123 |
Number of Participants With Dose Limiting Toxicities (DLTs)
DLTs were AEs considered related to study drug that prevented escalation of the drug dose. Hematologic DLTs included any Grade 5 hematologic toxicity, Grade 4 neutropenia lasting for ≥7 days in duration, Grade 3 or Grade 4 neutropenia with fever >38.5°C and/or infection requiring antibiotic or anti-fungal treatment, and Grade 4 thrombocytopenia (≤25.0 x 10^9/L). Non-hematologic DLT was defined as any Grade 3, 4, or 5 non-hematologic toxicity, with the specific exceptions of: Grade 3 nausea or Grade 3 vomiting, Grade 3 diarrhea, or Grade 3 dehydration occurring in the setting of inadequate compliance with supportive care and lasting for <48 hours, alopecia, inadequately treated hypersensitivity reactions, or Grade 3 elevated transaminases of ≤1 week in duration. Any drug-related AE leading to a dose modification of MK-5108, or any unresolved drug-related toxicity persisting>6 weeks, was also considered a DLT. (NCT00543387)
Timeframe: Day 1 to Day 21 of study treatment (Cycle 1 for Panel 1, Panel 2, or Crossover)
| Intervention | Participants (Count of Participants) |
|---|
| MK-5108 200 mg BID (Panel 1) | 0 |
| MK-5108 400 mg BID (Panel 1) | 0 |
| MK-5108 800 mg BID (Panel 1) | 0 |
| MK-5108 1200 mg BID (Panel 1) | 0 |
| MK-5108 1500 mg BID (Panel 1) | 0 |
| MK-5108 1800 mg BID (Panel 1) | 0 |
| MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2) | 1 |
| MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2) | 0 |
| MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2) | 2 |
| MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover) | 0 |
| MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover) | 0 |
Number of Participants Who 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 product, 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 the Sponsor's product, was also an AE. The number of participants who experienced an AE was reported for each dose level group. (NCT00543387)
Timeframe: From Day 1 of study treatment until 30 days following the last dose of study treatment (up to 577 days)
| Intervention | Participants (Count of Participants) |
|---|
| MK-5108 200 mg BID (Panel 1) | 3 |
| MK-5108 400 mg BID (Panel 1) | 3 |
| MK-5108 800 mg BID (Panel 1) | 3 |
| MK-5108 1200 mg BID (Panel 1) | 3 |
| MK-5108 1500 mg BID (Panel 1) | 3 |
| MK-5108 1800 mg BID (Panel 1) | 3 |
| MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Panel 2) | 6 |
| MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Panel 2) | 6 |
| MK-5108 225 mg BID + 60 mg/m^2 Docetaxel (Panel 2) | 5 |
| MK-5108 100 mg BID + 60 mg/m^2 Docetaxel (Crossover) | 1 |
| MK-5108 150 mg BID + 60 mg/m^2 Docetaxel (Crossover) | 3 |
Progression-free Survival
Estimated using the product-limit method of Kaplan and Meier. Progression defined as a 50% increase or an increase of 10 cm^2 (whichever is smaller) in the sum of all measurable lesions over smallest sum observed (over baseline if no decrease) using the same techniques as baseline, or clear worsening of any evaluable disease, or reappearance of any lesion that had disappeared, or appearance of any new lesion/site, or failure to return for evaluation due to death or deteriorating condition. Progression-free survival defined as from first day of treatment until the date of first documented progression or date of death from any cause, whichever came first. If failure has not occurred, failure time is censored at the time of last follow-up. (NCT00544414)
Timeframe: From date of initial treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 171 months
| Intervention | Months (Median) |
|---|
| Treatment | 170.5 |
Overall Response
Complete response (CR): Complete disappearance of all measurable and evaluable disease. No new lesions. Partial response (PR): Greater than or equal 50% decrease under baseline in the sum of products of perpendicular diameters of all measurable lesions. No new lesions. All measurable and evaluable lesions and sites must be assessed using the same techniques as baseline. Overall Response (OR) = CR + PR. (NCT00544414)
Timeframe: 30 days after last course of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Treatment | 28 |
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by X-Ray/Mammography
Clinical response was determined based on tumor measurements by sponsor in combination with tumor response assessment by investigator. Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Overall response is derived based on the sum total of breast tumors and all nodes examined. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| Primary Breast Tumor (n=71,58,61,47) | Overall Response (n=71,53,55,43) |
|---|
| Pertuzumab+Docetaxel | 66.0 | 65.1 |
,| Trastuzumab+Docetaxel | 67.6 | 67.6 |
,| Trastuzumab+Pertuzumab | 49.2 | 47.3 |
,| Trastuzumab+Pertuzumab+Docetaxel | 65.5 | 67.9 |
Percentage of Participants Achieving Clinical Response During Neo-Adjuvant Period by Clinical Examination
Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. Primary breast tumor clinical response is based on primary breast tumor assessment. Overall response is derived based on the sum total of breast tumors and all nodes examined. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| Primary Breast Tumor (n=99,101,102,91) | Overall Response (n=97,100,98,88) |
|---|
| Pertuzumab+Docetaxel | 71.4 | 73.9 |
,| Trastuzumab+Docetaxel | 79.8 | 81.4 |
,| Trastuzumab+Pertuzumab | 67.6 | 66.3 |
,| Trastuzumab+Pertuzumab+Docetaxel | 88.1 | 88.0 |
Percentage of Participants Achieving pCR by Presence or Absence of Residual Intraductal Carcinoma (DCIS) / Intalobular Carcinoma (LCIS)
pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders. (NCT00545688)
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
| Intervention | percentage of participants (Number) |
|---|
| pCR Achieved and No residual DCIS/LCIS at Surgery | pCR Achieved and Residual DCIS/LCIS at Surgery |
|---|
| Pertuzumab+Docetaxel | 17.7 | 6.3 |
,| Trastuzumab+Docetaxel | 16.8 | 12.1 |
,| Trastuzumab+Pertuzumab | 9.3 | 7.5 |
,| Trastuzumab+Pertuzumab+Docetaxel | 36.4 | 9.3 |
Percentage of Participants Achieving Best Primary Tumor Response (Complete Response [CR], Partial Response [PR], Stable Disease [SD] or Disease Progression [PD]) During Neo-Adjuvant Treatment by X-Ray/Mammography
Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is greater than (>)0 at screening or cycle 1 Day 1; PR: if measurement is at least a 30 percent (%) decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at, Baseline and Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Pertuzumab+Docetaxel | 19.1 | 46.8 | 34.0 | 0.0 |
,| Trastuzumab+Docetaxel | 18.3 | 49.3 | 31.0 | 1.4 |
,| Trastuzumab+Pertuzumab | 13.1 | 36.1 | 44.3 | 6.6 |
,| Trastuzumab+Pertuzumab+Docetaxel | 19.0 | 46.6 | 32.8 | 1.7 |
Percentage of Participants Achieving Best Primary Breast Tumor Response (CR, PR, SD or PD) During Neo-Adjuvant Period by Clinical Examination
Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for primary breast tumor using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Pertuzumab+Docetaxel | 20.9 | 50.5 | 28.6 | 0.0 |
,| Trastuzumab+Docetaxel | 23.2 | 56.6 | 20.2 | 0.0 |
,| Trastuzumab+Pertuzumab | 16.7 | 51.0 | 30.4 | 2.0 |
,| Trastuzumab+Pertuzumab+Docetaxel | 30.7 | 57.4 | 11.9 | 0.0 |
Percentage of Participants With Progressive Disease During Neo-Adjuvant Treatment Period
Tumor assessments were made based upon the Response Evaluation Criteria in Solid Tumors (RECIST) criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: PD: if lesion is at least a 20 % increased from measurements at baseline. Percentage of participants along with 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method were reported. Missing investigator assessments were considered as no progressive disease. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab+Docetaxel | 0.0 |
| Trastuzumab+Pertuzumab+Docetaxel | 0.9 |
| Trastuzumab+Pertuzumab | 7.5 |
| Pertuzumab+Docetaxel | 2.1 |
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During Neo-Adjuvant Period by X-Ray/Mammography
Tumor assessments were made based on the RECIST criteria - version 1.0 The overall response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Pertuzumab+Docetaxel | 18.6 | 46.5 | 34.9 | 0.0 |
,| Trastuzumab+Docetaxel | 18.3 | 49.3 | 31.0 | 1.4 |
,| Trastuzumab+Pertuzumab | 12.7 | 34.5 | 45.5 | 7.3 |
,| Trastuzumab+Pertuzumab+Docetaxel | 18.9 | 49.1 | 30.2 | 1.9 |
Percentage of Participants Achieving Pathological Complete Response (pCR)
pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants with invalid/missing pCR assessments were defined as non-responders (NCT00545688)
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab+Docetaxel | 29.0 |
| Trastuzumab+Pertuzumab+Docetaxel | 45.8 |
| Trastuzumab+Pertuzumab | 16.8 |
| Pertuzumab+Docetaxel | 24.0 |
Time to Clinical Response During Neo-Adjuvant Treatment Period
Time to clinical response was defined as the time from the date of first dose received to the date of assessment of clinical response. Time to Clinical response was determined by Kaplan-Meier estimates. Tumor assessments were made based on the RECIST criteria - version 1.0. The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes). Clinical Responders are participants who have achieved CR or PR during the Neo-adjuvant treatment. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | months (Median) |
|---|
| Trastuzumab+Docetaxel | 6.3 |
| Trastuzumab+Pertuzumab+Docetaxel | 6.3 |
| Trastuzumab+Pertuzumab | 6.9 |
| Pertuzumab+Docetaxel | 7.3 |
Percentage of Participants Achieving Breast Conserving Surgery For Whom Mastectomy Was Planned
Breast Conserving Surgery (BCS) was defined as quadrantectomy, lumpectomy, no surgery, sentinel node biopsy, axillary surgical resection or other method of avoiding mastectomy. (NCT00545688)
Timeframe: Surgery (Within 2 weeks after Cycle 4) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab+Docetaxel | 22.6 |
| Trastuzumab+Pertuzumab+Docetaxel | 23.2 |
| Trastuzumab+Pertuzumab | 18.0 |
| Pertuzumab+Docetaxel | 31.7 |
Percentage of Participants Who Were Progression Free and Disease Free
Disease-free survival (DFS) was defined as the time from first date of no disease to first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from the study without documented progression and for whom evaluations were made, were censored at date of last assessment when participant was known to be disease-free. Progression-free survival (PFS) was defined as time from date of randomization to first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. Participants who were withdrawn from study without documented progression and for whom evaluations were made, were censored at date of last assessment when the participant was known to be free from progressive disease. Participants without post baseline assessments but known to be alive were censored at the time of randomization. (NCT00545688)
Timeframe: Randomization up to a maximum of 329 weeks
| Intervention | percentage of participants (Number) |
|---|
| Progression Free | Disease Free |
|---|
| Pertuzumab+Docetaxel | 75.0 | 76.1 |
,| Trastuzumab+Docetaxel | 82.2 | 82.5 |
,| Trastuzumab+Pertuzumab | 74.8 | 80.2 |
,| Trastuzumab+Pertuzumab+Docetaxel | 84.1 | 85.1 |
Progression Free and Disease Free Survival
DFS was defined as the time from the first date of no disease (date of surgery) to the first documentation of PD or death. Participants without progression after surgery were considered Disease Free. Any evidence of contralateral disease in-situ was not considered as PD. PFS was defined as the time from the date of randomization to the first documentation of PD or death. Any evidence of contralateral disease in-situ was not considered as PD. DFS and PFS were determined using Kaplan-Meier estimates. (NCT00545688)
Timeframe: Randomization up to a maximum of 329 weeks
| Intervention | percentage of participants (Median) |
|---|
| PFS | DFS |
|---|
| Pertuzumab+Docetaxel | NA | NA |
,| Trastuzumab+Docetaxel | NA | NA |
,| Trastuzumab+Pertuzumab | NA | NA |
,| Trastuzumab+Pertuzumab+Docetaxel | 71.0 | 67.2 |
Percentage of Participants Achieving pCR by Hormone Receptor Status
pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Participants were classified as Estrogen and/or Progesterone positive (+ve), Estrogen and/or Progesterone negative (-ve) or receptor status unknown. Participants with invalid/missing pCR assessments were defined as non-responders. (NCT00545688)
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
| Intervention | percentage of participants (Number) |
|---|
| Estrogen and/or Progesterone +ve (n=50,50,51,46) | Estrogen and/or Progesterone -ve (n=57,57,55,50) | Receptor Status Unknown (0,0,1,0) |
|---|
| Pertuzumab+Docetaxel | 17.4 | 30.0 | NA |
,| Trastuzumab+Docetaxel | 20.0 | 36.8 | NA |
,| Trastuzumab+Pertuzumab | 5.9 | 27.3 | 0.0 |
,| Trastuzumab+Pertuzumab+Docetaxel | 26.0 | 63.2 | NA |
Percentage of Participants Achieving pCR by Lymph Node Status
pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Lymph node status was defined as either negative lymph node at surgery or positive lymph node at surgery. Participants with invalid/missing pCR assessments were defined as non-responders. (NCT00545688)
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
| Intervention | percentage of participants (Number) |
|---|
| pCR achieved and Negative Lymph Nodes at Surgery | pCR achieved and Positive Lymph Nodes at Surgery |
|---|
| Pertuzumab+Docetaxel | 17.7 | 6.3 |
,| Trastuzumab+Docetaxel | 21.5 | 7.5 |
,| Trastuzumab+Pertuzumab | 11.2 | 5.6 |
,| Trastuzumab+Pertuzumab+Docetaxel | 39.3 | 6.5 |
Percentage of Participants Achieving pCR by Breast Cancer Type
pCR was defined as an absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. Based on the type of breast cancer participants were categorized as those with 1. Operable breast cancer, 2. Inflammatory breast cancer and 3. Locally advanced breast cancer. Participants with invalid/missing pCR assessments were defined as non-responders. (NCT00545688)
Timeframe: Approximately 4 months from randomization following surgery or early withdrawal, whichever occurred first (Surgery was performed within 2 weeks after Cycle 4)
| Intervention | percentage of participants (Number) |
|---|
| Operable Breast Cancer (n=64,65,65,60) | Inflammatory Breast Cancer (n=7,10,7,5) | Locally Advance Breast Cancer (36,32,35,31) |
|---|
| Pertuzumab+Docetaxel | 26.7 | 40.0 | 16.1 |
,| Trastuzumab+Docetaxel | 23.4 | 14.3 | 41.7 |
,| Trastuzumab+Pertuzumab | 16.9 | 28.6 | 14.3 |
,| Trastuzumab+Pertuzumab+Docetaxel | 47.7 | 40.0 | 43.8 |
Percentage of Participants Achieving Best Overall Response (CR, PR, SD or PD) During the Neo-Adjuvant Period by Clinical Examination
Tumor assessments were made based on the RECIST criteria - version 1.0 The clinical response at each cycle up to the last assessment prior to surgery was derived for: i) the primary breast lesion; (ii) across secondary breast lesions, (iii) across all breast lesions (iv) across axillary nodes (v) across supraclavicular nodes and (vi) across all nodes (vii) across all lesions (overall) using the following algorithm: CR: if measurement of '0' is noted at a given cycle as compared to baseline measurement which is >0 at screening or cycle 1 day 1; PR: if measurement is at least a 30% decreased compared to baseline levels . (Reference= baseline size or sum of sizes); SD: if measurement at a given cycle is not sufficient shrinkage to qualify for neither PR nor sufficient increase to qualify for PD compared to baseline levels. PD: if lesion is at least a 20 % increase from measurements at baseline. Overall response is derived based on the sum total of breast tumors and all nodes examined. (NCT00545688)
Timeframe: Baseline up to Cycle 4 (assessed at Baseline, Day 1 of Cycles 1-4 Pre-Surgery) Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| CR | PR | SD | PD |
|---|
| Pertuzumab+Docetaxel | 15.9 | 58.0 | 26.1 | 0.0 |
,| Trastuzumab+Docetaxel | 21.6 | 59.8 | 17.5 | 1.0 |
,| Trastuzumab+Pertuzumab | 11.2 | 55.1 | 31.6 | 2.0 |
,| Trastuzumab+Pertuzumab+Docetaxel | 25.0 | 63.0 | 12.0 | 0.0 |
Percentage of Nontriple-negative (NTN) Participants With Best Response to Treatment of Complete or Partial Per Cohort
The tumor response rate is defined as the total number of participants whose best response is CR or PR, divided by the number of randomized participants. Participants not evaluable for response are considered to be nonresponders. NTN participants are who are not TN participants (TN participants are those with tumors that do not express estrogen or progesterone receptors and that do not overexpress HER2) and who received ixabepilone plus capecitabine or docetaxel plus capecitabine. (NCT00546364)
Timeframe: Baseline to 6 weeks (end of Cycle 2)
| Intervention | Percentage of NTN Participants (Number) |
|---|
| Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 | 33 |
| Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 | 54 |
| Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2 | 42 |
Percentage of Participants With Best Response to Treatment of Complete or Partial
The tumor response rate is defined as the number of participants with a best tumor response of CR or PR (as assessed by the investigator according to RECIST criteria), divided by the number of participants randomized in that arm. (NCT00546364)
Timeframe: Baseline to 6 weeks (end of Cycle 2)
| Intervention | Percentage of patients (Number) |
|---|
| Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 | 35 |
| Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 | 41 |
| Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2 | 30 |
Number of Participants With Abnormalities in Hematology Laboratory Results by Worst Common Terminology Criteria (CTC) Grade
CTC Grade 1=Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2=Moderate; minimal, local or noninvasive intervention indicated. Grade 3=Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4=Life-threatening consequences; urgent intervention indicated. (NCT00546364)
Timeframe: Baseline in Cycle 1 (21 days) and then prior to start of each 21-day cycle
| Intervention | Participants (Number) |
|---|
| Neutropenia (Grades 1-4) | Neutropenia (Grade 3 or 4) | Leukopenia (Grades 1-4) | Leukopenia (Grade 3 or 4) | Thrombocytopenia (Grades 1-4) | Thrombocytopenia (Grade 3 or 4) | Anemia (Grades 1-4) | Anemia (Grade 3 or 4) |
|---|
| Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2 | 17 | 15 | 17 | 12 | 7 | 0 | 17 | 0 |
,| Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 | 15 | 10 | 19 | 9 | 11 | 1 | 21 | 1 |
,| Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 | 18 | 12 | 20 | 9 | 9 | 0 | 18 | 0 |
Number of Participants With Abnormalities in Serum Chemistry Laboratory Results
ULN=Upper limit of normal among all laboratory ranges. Alanine aminotransferase (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. Aspartate aminotransferase (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. Creatine Grade 1: >ULN to 1.5*ULN; Grade 2: 1.5 to 3.0*ULN; Grade 3: >3.0 to 6.0*ULN; Grade 4: >6.0*ULN. (NCT00546364)
Timeframe: Baseline in Cycle 1 (21 days) and then prior to start of each 21-day cycle
| Intervention | Participants (Number) |
|---|
| ALT, high (Grades 1-4) | ALT, high (Grade 3 or 4) | AST, high (Grades 1-4) | AST, high (Grade 3 or 4) | Total bilirubin, high (Grades 1-4) | Total bilirubin, high (Grade 3 or 4) | Creatinine, high (Grades 1-4) | Creatinine, high (Grade 3 or 4) |
|---|
| Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2 | 5 | 0 | 5 | 0 | 0 | 0 | 2 | 0 |
,| Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 | 3 | 0 | 5 | 0 | 1 | 0 | 1 | 0 |
,| Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 | 4 | 0 | 7 | 0 | 0 | 0 | 1 | 0 |
Number of Participants With Best Tumor Response as Assessed With Response Evaluation Criteria in Solid Tumors (RECIST)
RECIST definitions: Complete reponse (CR)=disappearance of all nontarget lesions; partial response (PR)=at least 30% reduction in the sum of the longest diameter (LD) of all target lesions in reference to the baseline sum LD; stable disease (SD)=neither PR nor progressive disease (PD) criteria were met; PD=at least 20% increase in the sum of the LD of all target lesions, taking as reference the smallest sum LD recorded at or following baseline. Tumor status assessed by investigator. (NCT00546364)
Timeframe: Baseline to 6 weeks (end of Cycle 2)
| Intervention | Participants (Number) |
|---|
| Complete response (CR) | Partial response (PR) | Stable disease (SD) | Progressive disease (PD) | Discontinued before first tumor assessment | No tumor assessment due to other reasons | Unable to determine |
|---|
| Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2 | 0 | 6 | 3 | 9 | 1 | 1 | 0 |
,| Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 | 1 | 8 | 3 | 9 | 0 | 0 | 1 |
,| Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 | 1 | 6 | 6 | 4 | 3 | 0 | 0 |
Percentage of Triple-negative (TN) Participants With Best Response to Treatment of Complete or Partial
The tumor response rate is defined as the total number of participants whose best response is CR or PR, divided by the number of randomized participants. Participants not evaluable for response are considered to be nonresponders. TN participants are those with tumors that do not express estrogen or progesterone receptors and that do not over express human epidermal growth factor receptor 2 (HER2). (NCT00546364)
Timeframe: Baseline to 6 weeks (end of Cycle 2)
| Intervention | Percentage of TN Participants (Number) |
|---|
| Ixabepilone, 40 mg/m^2 + Capecitabine, 1000 mg/m^2 | 38 |
| Ixabepilone, 32 mg/m^2 + Capecitabine, 1000 mg/m^2 | 22 |
| Docetaxel, 75 mg/m^2 + Capecitabine, 1000 mg/m^2 | 13 |
Proportion of Patients With Pathologic Complete Response
After neoadjuvant therapy, participants underwent surgical resection. The excised tumor was examined by a pathologist. A pathologic complete response is defined as the absence of any histopathologic evidence of tumor in the resected esophageal and nodal tissue specimen. (NCT00551759)
Timeframe: At time of surgery (which occurred 63 to 91 days after study entry)
| Intervention | Proportion of patients (Number) |
|---|
| Neoadjuvant Therapy, Surgery, Adjuvant Therapy | 0.33 |
Duration of Overall Survival in All Participants (Data Cutoff 07 September 2010)
OS was determined from the date of randomization to the date of death irrespective of the cause of death. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months
| Intervention | months (Median) |
|---|
| Comparator | 5.5 |
| Erlotinib | 5.3 |
Percentage of Participants Who Died in Epidermal Growth Factor Receptor (EGFR) Positive and Negative Population
EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by immunohistochemistry (IHC). OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| EGFR Positive (n=149,143) | EGFR Negative (n=39,32) |
|---|
| Comparator | 79.9 | 79.5 |
,| Erlotinib | 76.9 | 75.0 |
Duration of OS in EGFR Positive and Negative Population
EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Death or Until Data Cut off (07 September 2010) up to 52 months
| Intervention | months (Median) |
|---|
| EGFR Positive (n=149,143) | EGFR Negative (n=39,32) |
|---|
| Comparator | 5.5 | 6.7 |
,| Erlotinib | 5.6 | 5.4 |
Time to Symptomatic Progression Using FACT-L
Participants' responses on the FACT-L were scored according to FACIT measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. Kaplan Meier estimated were used for analysis. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months
| Intervention | weeks (Median) |
|---|
| Comparator | 9.0 |
| Erlotinib | 7.1 |
Time to Deterioration in the TOI
TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. 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. The clinically meaningful decline used to determine deterioration in TOI was ≥6- point decline from baseline. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months
| Intervention | weeks (Median) |
|---|
| Comparator | 9.3 |
| Erlotinib | 6.7 |
Time to Deterioration in Quality of Life Using FACT-L
The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Time to deterioration of QoL or symptom progression is defined as time from randomization until either a clinically meaningful decline from baseline in Total FACT-L or, death on study, whichever occurs first. The clinically meaningful decline that was 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. Kaplan-Meier estimate was used to determine time to event. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months
| Intervention | weeks (Median) |
|---|
| Comparator | 9.0 |
| Erlotinib | 6.3 |
Progression-Free Survival (PFS) in All Participants (Data Cutoff 07 September 2010)
Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease 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 one or more new lesions. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months
| Intervention | weeks (Median) |
|---|
| Comparator | 8.6 |
| Erlotinib | 6.3 |
Probable Percentage of Participants With Symptomatic Progression at 6 Months as Assessed by FACT-L
Participants' responses on the FACT-L were scored according to FACIT measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. Kaplan Meier estimated were used for analysis. (NCT00556322)
Timeframe: 6 Months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 27 |
| Erlotinib | 27 |
Probable Percentage of Participants With Deterioration in the TOI at 6 Months as Assessed by FACT-L
TOI is defined as the sum of the scores of the PW, FWB, and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. 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. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: 6 Months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 28 |
| Erlotinib | 21 |
PFS in EGFR Positive and Negative Population (Data Cutoff 07 September 2010)
EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months
| Intervention | weeks (Median) |
|---|
| EGFR Positive (n=149,143) | EGFR Negative (n=39,32) |
|---|
| Comparator | 8.9 | 11.5 |
,| Erlotinib | 6.3 | 6.7 |
Probable Percentage of Participants Remaining Without Deterioration in Quality of Life at 6 Months as Assessed by FACT-L
The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the FACT-G and the LCS. The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. Kaplan Meier estimates were used for analysis. (NCT00556322)
Timeframe: 6 Months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 25.0 |
| Erlotinib | 19.0 |
Probable Percentage of Participants Remaining Alive at 1 Year
OS was determined from the date of randomization to the date of death irrespective of the cause of death. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: 1 Year
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 24.0 |
| Erlotinib | 26.0 |
Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months
Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease 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 one or more new lesions. Event free estimates were determined using Kaplan-Meier estimates. (NCT00556322)
Timeframe: 6 Months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 17.0 |
| Erlotinib | 13.0 |
Percentage of Participants With Symptomatic Progression Using FACT-L
Participants' responses on the FACT-L were scored according to the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system manual. Time to symptom progression is the time from randomization until the earlier of a clinically meaningful decline from baseline in LCS score, or death on study. A change in 2 to 3 points on the LCS is a clinically meaningful change. Meaningful declines in scores as measured by the FACIT instruments have been found to be larger than improvements. Thus, deterioration in disease-related symptoms was defined by the upper bound (3 points) of the range of clinically meaningful change. However, participants who demonstrated early lung cancer progression demonstrated smaller changes from baseline score on the LCS. Therefore, the clinically meaningful decline that was used to determine progression of symptoms in this study was at least 1.5-point decline in LCS score from baseline. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 60.6 |
| Erlotinib | 62.0 |
Percentage of Participants With Disease Progression or Death (All Participants; Data Cut Off 07 September 2010)
Tumor response was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria (version 1.0). Progressive Disease was defined as at least a 20 percent (%) 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. The primary analysis of PFS used objective progression (RECIST) plus clinical progression (based on relevant clinical findings - if any). A further assessment of PFS was made on objective (radiological) progression. If clinical progression was diagnosed first, the participant was censored at the date of the last tumor assessment, where non-progression was documented. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Until Data Cut off (07 September 2010) up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 83.3 |
| Erlotinib | 92.6 |
Percentage of Participants With Deterioration in the Trial Outcome Index (TOI)
TOI is defined as the sum of the scores of the Physical Well- Being (PWB), Functional Well-Being (FWB), and LCS of the FACT-L instrument. Trial Outcome Index measures the physical functioning of participants. 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. The clinically meaningful decline used to determine deterioration in TOI was ≥6-point decline from baseline. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 60.0 |
| Erlotinib | 63.3 |
Percentage of Participants With Deterioration in Quality of Life Determined Using Functional Assessment of Cancer Therapy - Lung (FACT-L)
The FACT-L measures health related QOL and composes of five domains: the four domains (physical well being, emotional well being, social well being, functional well being) from the Functional Assessment of Cancer Treatment-General scale (FACT-G) and the lung cancer subscale (LCS). The FACT-L total score ranges from 0 to 136, higher scores represent better QOL. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 66.1 |
| Erlotinib | 66.9 |
Percentage of Participants Who Died (All Participants; Data Cutoff: 07 September 2010)
Overall survival (OS) was determined from the date of randomization to the date of death irrespective of the cause of death. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 or Death and Every 12 Weeks until Death or Data Cut off (07 September 2010) up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 81.0 |
| Erlotinib | 77.8 |
Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator Using RECIST
Best overall response was defined as the best response according to RECIST recorded from the date of randomization until disease progression or recurrence. CR: disappearance of all target lesions; PR: reduction by at least 30% of the sum of the longest diameters of each target lesion, taking the initial sum of the longest diameters as a reference; Stable disease (SD): insufficient tumor reduction to define partial response and/or tumor increase less than that necessary to define tumor progression, taking as a reference the smallest sum of the longest diameter since the start of treatment; Progressive Disease (PD): increase by at least 20% in the sum of LD 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. 95% Confidence Interval (CI) for one sample binomial using Pearson-Clopper method. Participants with a missing response were considered non-responders. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity or Death or up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| Comparator | 6.3 |
| Erlotinib | 7.9 |
Probable Percentage of Participants Remaining Alive at 1 Year in the EGFR Positive and Negative Population
EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. OS was determined from the date of randomization to the date of death irrespective of the cause of death in EGFR positive and negative populations. Kaplan-Meier estimates were used for analysis. (NCT00556322)
Timeframe: 1 Year
| Intervention | percentage of participants (Number) |
|---|
| EGFR Positive (n=30,32) | EGFR Negative (n=8,4) |
|---|
| Comparator | 27.0 | 28.0 |
,| Erlotinib | 30.0 | 20.0 |
Probable Percentage of Participants Remaining Alive and Progression Free at 6 Months in EGFR Positive and Negative Population
EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC. Tumor response was evaluated according to RECIST criteria (version 1.0). PFS was defined as time from randomization to the date of documented disease progression or death, whichever occurred first in EGFR positive and negative populations. Participants without progression were censored at the date of last tumor assessment where non progression was documented. If a participant receives a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Event free estimates were determined using Kaplan-Meier estimates. (NCT00556322)
Timeframe: 6 Months
| Intervention | percentage of participants (Number) |
|---|
| EGFR Positive (n=23,18) | EGFR Negative (n=4,5) |
|---|
| Comparator | 20.0 | 11.0 |
,| Erlotinib | 13.0 | 16.0 |
Percentage of Participants With Disease Progression or Death in EGFR Positive and Negative Population (Data Cut Off 07 September 2010)
EGFR is a gene in the tumor tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR was determined by IHC.Tumor response was evaluated according to RECIST criteria (version 1.0). Progressive Disease 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 one or more new lesions. (NCT00556322)
Timeframe: Baseline, Weeks 3 and 6, Every 3 Weeks until Week 48 and Every 12 Weeks until Disease Progression or unacceptable toxicity up to 52 months
| Intervention | percentage of participants (Number) |
|---|
| EGFR Positive (n=149,143) | EGFR Negative (n=39,32) |
|---|
| Comparator | 79.9 | 89.7 |
,| Erlotinib | 93.7 | 90.6 |
Percentage of Participants With pCR by Hypoxia Inducible Factor (HIF) Protein Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. HIF protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| No expression (n=25) | Normal (n=8) | Augmented expression (n=5) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 40.0 | 12.5 | 60.0 |
Percentage of Participants With pCR by Insulin-Like Growth Factor (IGF) Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. IGF gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=0) | Gene expression below housekeeping level (n=34) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | NA | 32.4 |
Percentage of Participants With pCR by KISS1 Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. KISS1 gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=1) | Gene expression below housekeeping level (n=33) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 0.0 | 33.3 |
Percentage of Participants With pCR by KISS1 Protein Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. KISS1 protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| No expression (n=18) | Normal (n=3) | Augmented expression (n=4) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 27.8 | 66.7 | 50.0 |
Percentage of Participants With pCR by Kisspeptin (KISS1) Amplification
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. KISS1 amplification was defined as 1 (aneuploid), 2 (normal), 4 (amplification), or NE (not evaluated). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Anueploid (n=8) | Normal (n=13) | Amplification (n=2) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 12.5 | 30.77 | 50.0 |
Percentage of Participants With pCR by Phosphorylated AKT (pAKT) Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. pAKT gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=0) | Gene expression below housekeeping level (n=34) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | NA | 32.4 |
Percentage of Participants With pCR by Vascular Endothelial Growth Factor Receptor (VEGFR) Amplification
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEFGR amplification was defined as 1 (aneuploid), 2 (normal), 4 (amplification), or NE (not evaluated). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Anueploid (n=1) | Normal (n=18) | Amplification (n=4) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 0 | 33.3 | 0 |
Percentage of Participants With pCR by Proliferation of Ki67
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. Biomarker Ki67 proliferation was defined as low (less than [<]15% ) and high (≥15%). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| High proliferative index (n=50) | Low proliferative index (n=15) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 24.0 | 13.3 |
Percentage of Participants With pCR by Phosphorylated MAP Kinase (pMAPK) Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. pMAPK gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=30) | Gene expression equal to housekeeping level (n=1) | Gene expression below housekeeping level (n=3) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 33.3 | 0 | 33.3 |
Percentage of Participants With Objective Clinical Response
Overall clinical response is the best response obtained through physical examination and/or radiological tests after completion of chemotherapy cycles. The 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) and was categorized as clinical response (CR+PR) or clinical benefit (CR+PR+ no change [NC]). Per RECIST, CR was defined as disappearance of all target lesions, non-target lesions, and normalization of tumor marker level. PR was 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 the criteria for response were first met. (NCT00559754)
Timeframe: Within 28 days of enrollment, Weeks 12 and 24
| Intervention | percentage of participants (Number) |
|---|
| CR+PR | CR+PR+NC |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 88.9 | 98.6 |
Percentage of Participants With pCR by Angiotension Protein Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. Angiotensin protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| No expression (n=14) | Normal (n=1) | Augmented expression (n=11) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 7.1 | 0.0 | 63.6 |
Percentage of Participants With pCR by Endothelial Nitric Oxide Synthase (ENOS) Protein Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. ENOS protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| No expression (n=24) | Normal (n=10) | Augmented expression (n=4) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 29.2 | 40.0 | 25.0 |
Percentage of Participants With Breast-Conserving Surgery
Breast-conserving surgery was defined as lumpectomy + lymphadenectomy (LA), segmentectomy + LA, quadrantectomy + LA, or other (including sentinal node extirpation tumorectomy). (NCT00559754)
Timeframe: Week 24
| Intervention | percentage of participants (Number) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 62.7 |
Percentage of Participants With pCR by ENOS Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. ENOS gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=1) | Gene expression below housekeeping level (n=33) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 0 | 33.3 |
Percentage of Participants With Pathological Complete Response (pCR)
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria: 1) the primary tumor was Grade 5 (no malignant cells identified at the location of the primary tumor (ductal carcinoma in situ may be present); 2) no involvement was identified in the lymph nodes; 3) the tumour size at evaluation of the surgical piece was 0 centimeters (cm); and 4) the pathological staging of the tumour from the surgical piece was pT0pN0pM0, the stage is not applicable (NA). It will only be considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 24.2 |
Percentage of Participants With pCR by Angiotensin II Receptor Type I (AGTR) Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. AGTR gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=0) | Gene expression below housekeeping level (n=33) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | NA | 30.3 |
Percentage of Participants With pCR by HIF Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. HIF gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=9) | Gene expression below housekeeping level (n=25) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 44.4 | 28.0 |
Percentage of Participants With pCR by Vascular Endothelial Growth Factor (VEGF) Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEGF gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=1) | Gene expression below housekeeping level (n=33) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 100.0 | 30.3 |
Percentage of Participants With pCR by RKISS1 Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. RKISS1 gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=0) | Gene expression below housekeeping level (n=34) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | NA | 32.4 |
Percentage of Participants With pCR by VEGFR Protein Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEGFR protein expression was defined as 0 (no expression), 1 (normal), 2 (augmented expression), or NE (not evaluated). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| No expression (n=7) | Normal (n=5) | Augmented expression (n=10) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 28.6 | 40.0 | 20.0 |
Percentage of Participants With pCR by VEGFR Gene Expression
The percentage of participants with pCR was determined by anatomopathological study after completion of 8 cycles of study treatment. The anatomopathological study of the surgical piece was performed and assessed according to the Miller-Payne criteria. It was only considered pCR in the case of absence of invasive tumour cells in the breast and lymph nodes. VEGFR gene expression was defined as below the housekeeping reference level (>0), above the housekeeping reference level (<0), or equal to the housekeeping reference level (0). (NCT00559754)
Timeframe: After Week 24 (surgery)
| Intervention | percentage of participants (Number) |
|---|
| Gene expression above housekeeping level (n=7) | Gene expression below housekeeping level (n=27) |
|---|
| Doxorubicin + Cyclophosphamide/Bevacizumab + Docetaxel | 0.0 | 40.7 |
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.
| Intervention | participants (Number) |
|---|
| Chemotherapy | 13 |
Overall Response (OR)
OR is classified as CR, partial response (PR), stable disease (SD), progressive disease (PD) or Unknown on completion of both induction and radiation treatment and assessed according to the Modified RECIST from the NCI. CR is defined as the disappearance of all target lesions (TLs) and non-TLs. PR is defined as ≥30% decrease in the sum of the longest diameters (LD) of TLs, taking as reference the disease measurement done at study entry. PD is defined as ≥20% increase in the sum of the LD of TLs, taking as a reference the smallest disease measurement recorded at study entry or the appearance of ≥1 new lesions or unequivocal progression of non-TLs. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. (NCT00565448)
Timeframe: after the completion of the consolidation treatment (up to 18 weeks)
| Intervention | participants (Number) |
|---|
| CR | PR | SD | PD | Unknown | Missing |
|---|
| Cisplatin/5-FU | 1 | 20 | 1 | 0 | 0 | 3 |
,| Docetaxel /Cisplatin/5-FU | 1 | 43 | 2 | 2 | 0 | 2 |
Docetaxel Area Under the Plasma Concentration-time Curve (AUC) in the Docetaxel/Cisplatin/5-FU Group
AUC estimated by Bayesian method using concentration-time data for each participant and the previously defined adult population model as prior information (with validity of the estimation verified). (NCT00565448)
Timeframe: Three plasma samples: one just before then 45 minutes and 5hour after the end of cycle 1 infusion
| Intervention | µg*h/mL (Mean) |
|---|
| Docetaxel/Cisplatin/5-FU | 3.43 |
Number of Participants With Complete Response (CR)
CR assessed by independent reviewers, according to the Modified Response Evaluation Criteria in Solid Tumors (RECIST) from the National Cancer Institute (NCI). Disease response evaluated after the completion of the induction treatment and prior to the radiation treatment. CR defined as the complete disappearance of the target and non-target lesion(s) identified at baseline after radiological evaluation by Magnetic Resonance Imaging (MRI) only. (NCT00565448)
Timeframe: after the completion of the induction treatment (up to 9 weeks)
| Intervention | participants (Number) |
|---|
| Docetaxel /Cisplatin/5-FU | 1 |
| Cisplatin/5-FU | 0 |
Overall Survival (OS) Rate
OS rate is the percentage of participants who survived 3 years after completion of consolidation treatment period. The Kaplan-Meier method was used to estimate OS rate. (NCT00565448)
Timeframe: 3 years after the end of the consolidation treatment period (up to 40 months from randomization)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel /Cisplatin/5-FU | 85.7 |
| Cisplatin/5-FU | 78.0 |
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
| Intervention | Participants (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 |
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.
| Intervention | Months (Median) |
|---|
| No Cytoreductive Surgery | 16.2 |
| Cytoreductive Surgery | 18.9 |
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
| Intervention | Months (Median) |
|---|
| Paclitaxel and Carboplatin Chemotherapy | 10.4 |
| Paclitaxel and Carboplatin Chemotherapy With Bevacizumab | 13.8 |
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.
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Prior to surgery | 6 weeks post-surgery | 15 weeks post-surgery | 6 months post-surgery | 12 months post-surgery |
|---|
| Cytoreductive Surgery | 74.2 | 68.4 | 68.8 | 73.5 | 75.6 |
,| No Cytoreductive Surgery | 74.5 | 69.3 | 68.7 | 72.6 | 74.0 |
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.
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Prior to cycle 1 (baseline) | Prior to cycle 3 | Prior to cycle 6 | 6 months post cycle 1 | 12 months post cycle 1 |
|---|
| Paclitaxel and Carboplatin Chemotherapy | 75.8 | 74.2 | 73.3 | 77.1 | 77.0 |
,| Paclitaxel and Carboplatin Chemotherapy With Bevacizumab | 75.3 | 73.4 | 72.3 | 77.2 | 77.8 |
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
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Prior to surgery (baseline) | 6 weeks post-surgery | 15 weeks post-surgery | 6 months post-surgery | 12 months post-surgery |
|---|
| Cytoreductive Surgery | 71.7 | 69.8 | 64.6 | 70.2 | 70.7 |
,| No Cytoreductive Surgery | 73.4 | 73.2 | 71.5 | 71.6 | 71.8 |
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.
| Intervention | score on a scale (Least Squares Mean) |
|---|
| Prior to cycle 1 (baseline) | Prior to cycle 3 | Prior to cycle 6 | 6 months post cycle 1 | 12 months post cycle 1 |
|---|
| Paclitaxel and Carboplatin Chemotherapy | 71.5 | 73.2 | 71.5 | 71.6 | 71.8 |
,| Paclitaxel and Carboplatin Chemotherapy With Bevacizumab | 69.4 | 69.8 | 64.6 | 70.2 | 70.7 |
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).
| Intervention | Months (Median) |
|---|
| Paclitaxel and Carboplatin Chemotherapy | 37.3 |
| Paclitaxel and Carboplatin Chemotherapy With Bevacizumab | 42.2 |
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)
| Intervention | Months (Median) |
|---|
| No Cytoreductive Surgery | 64.7 |
| Cytoreductive Surgery | 50.6 |
Baseline LVEF Value and Change in LVEF From Baseline at Maximum Absolute Decrease Value During the Treatment Period
All participants were required to have a left ventricular ejection fraction (LVEF) ≥50% at baseline, as measured by echocardiogram (preferred) or multiple-gated acquisition (MUGA) scan. The same method of LVEF assessment and the same institution/facility used at baseline was used throughout the study, to the extent possible. The baseline value was defined as the last valid value recorded during the pre-treatment period before or on study Day 1. The maximum absolute decrease in LVEF value was defined as the lowest post-baseline value up to the end of the overall study treatment period. Only data reported prior to the date of first crossover treatment were included for participants who crossed over from placebo to pertuzumab. (NCT00567190)
Timeframe: Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks)
| Intervention | Percentage points of LVEF (Mean) |
|---|
| Baseline (BL) LVEF Value | Change in LVEF From BL at Maximum Decrease Value |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 64.8 | -7.5 |
,| Placebo + Trastuzumab + Docetaxel | 65.6 | -7.3 |
Overall Number of Participants Who Experienced at Least One Adverse Event, Including Serious and Non-Serious Adverse Events, by Most Severe Intensity (According to NCI-CTCAE v3.0) During the Treatment Period
Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 3.0 (NCI-CTCAE v3.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death. Severe and serious are not synonymous. Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE. Only the most severe intensity was counted for multiple occurrences of the same AE in one participant. AEs reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks. (NCT00567190)
Timeframe: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
| Intervention | Participants (Count of Participants) |
|---|
| At Least One Serious AE - All Grades | At Least One Non-Serious AE - All Grades | At Least One AE - All Grades | At Least One AE - Grade 1 | At Least One AE - Grade 2 | At Least One AE - Grade 3 | At Least One AE - Grade 4 | At Least One AE - Grade 5 |
|---|
| Crossover From Placebo to Pertuzumab | 10 | 45 | 47 | 44 | 34 | 11 | 1 | 1 |
,| Pertuzumab + Trastuzumab + Docetaxel | 160 | 400 | 408 | 386 | 383 | 264 | 167 | 8 |
,| Placebo + Trastuzumab + Docetaxel | 116 | 386 | 391 | 368 | 350 | 229 | 158 | 12 |
Time to Symptom Progression
"Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale [BCS]). All items in the questionnaire were rated by the patient on a 5-point scale ranging from 0 (not at all) to 4 (very much). The total score ranged from 0 to 96. A higher score indicates better perceived quality of life. A positive change score from baseline indicates improvement. Symptom progression was defined as a decrease from baseline of 5 points or more." (NCT00567190)
Timeframe: Every 9 weeks from Baseline until investigator-determined progressive disease, up to the primary completion date (up to 3 years, 3 months)
| Intervention | Weeks (Median) |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 18.4 |
| Placebo + Trastuzumab + Docetaxel | 18.3 |
Overall Survival
Overall survival (OS) was the time from randomization to death from any cause, using Kaplan-Meier methodology. Survival data was collected every 18 weeks during the post-treatment follow-up period until death, loss to follow-up, or withdrawal of consent. Those who were alive, lost to follow up, or withdrew consent were censored at the latest date they participated in the study; those without post-baseline data were censored at 1 day. OS analyses were planned to take place at the primary completion date (First Interim), after 385 deaths (Event-Driven Final), and at the end of study (End-of-Study). A second interim OS analysis was planned due to a formal request from the European Medicines Agency. Median [range] time in weeks on study at each OS analysis (Pertuzumab vs. Placebo): First: 77.1 [0.7-165.3] vs. 73.1 [0.4-165.3]; Second: 117.1 [0.7-207.9] vs. 105.9 [0.4-207.9]; Event-Driven Final: 189.9 [0.7-304.1] vs. 140.5 [0.4-301.6]; End-of-Study: 201.8 [0.7-520.0] vs. 138.0 [0.4-514.7]. (NCT00567190)
Timeframe: From randomization to death from any cause, up to each respective analysis data cut-off date (see the Description field for the median time on study per treatment arm)
| Intervention | Months (Median) |
|---|
| End-of-Study OS Analysis | Event-Driven Final OS Analysis | Second Interim OS Analysis | First Interim OS Analysis |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 57.1 | 56.5 | NA | NA |
,| Placebo + Trastuzumab + Docetaxel | 40.8 | 40.8 | 37.6 | NA |
Number of Participants by Categories for the Maximum Absolute Decrease From Baseline in LVEF Value During the Treatment Period
All participants were required to have an left ventricular ejection fraction (LVEF) ≥50% at baseline, as measured by echocardiogram (preferred) or multiple-gated acquisition (MUGA) scan. The same method of LVEF assessment and the same institution/facility used at baseline was used throughout the study, to the extent possible. The baseline value was defined as the last valid value recorded during the pre-treatment period before or on study Day 1. The maximum absolute decrease in LVEF value was defined as the lowest post-baseline value up to the end of the overall study treatment period. Data reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks. (NCT00567190)
Timeframe: Every 9 weeks from the date of randomization until Treatment Discontinuation Visit (see Description for time on study treatment per arm)
| Intervention | Participants (Count of Participants) |
|---|
| LVEF Increase/No Change/Decrease FromBL <10%Points | LVEF <50% and Decrease From BL ≥10% to <15% Points | LVEF <50% and Decrease From BL ≥15% Points | LVEF ≥50% and Decrease From BL ≥10% Points | No Baseline (BL) LVEF Value |
|---|
| Crossover From Placebo to Pertuzumab | 30 | 0 | 3 | 15 | 1 |
,| Pertuzumab + Trastuzumab + Docetaxel | 249 | 7 | 21 | 115 | 2 |
,| Placebo + Trastuzumab + Docetaxel | 252 | 9 | 19 | 95 | 3 |
Number of Participants Who Experienced at Least One Adverse Event During the Post-Treatment Follow-Up Period
The post-treatment period was defined as the period following the treatment discontinuation visit. Only the following new adverse events (AEs) should have been reported during the post-treatment follow-up period: 1. Cardiac events (regardless of causality or seriousness) that started up to 1 year after the last dose, except for symptomatic left ventricular systolic dysfunction (regardless of causality) that started up to 3 years after the last dose; and 2. Treatment-related serious AEs, regardless of start date. AEs are listed by Medical Dictionary for Regulatory Activities, Version 21.1 (MedDRA v21.1) System Organ Class (SOC) and Preferred Term (PT); PTs fall under the SOC that is listed immediately above it in the table. Multiple occurrences of the same AE in one participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. (NCT00567190)
Timeframe: From Day 43 after discontinuation of all study medication to end of post-treatment follow-up period (up to 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Total with at Least One AE During Post-Treatment | Cardiac Disorders (SOC) | Left Ventricular Dysfunction (PT) | Cardiac Failure (PT) | Bundle Branch Block Left (PT) | Cardiopulmonary Failure (PT) | Myocardial Ischaemia (PT) | Pericardial Effusion (PT) | Prinzmetal Angina (PT) | General Disorders & Admin. Site Conditions (SOC) | Oedema Peripheral (PT) | Asthenia (PT) | Influenza Like Illness (PT) | Infections & Infestations (SOC) | Influenza (PT) | Viral Infection (PT) | Abscess Limb (PT) | Nasopharyngitis (PT) | Subcutaneous Abscess (PT) | Musculoskeletal & Connective Tissue Disorders(SOC) | Back Pain (PT) | Pain in Extremity (PT) | Nervous System Disorders (SOC) | Neuropathy Peripheral (PT) | Cognitive Disorder (PT) | Dizziness (PT) | Headache (PT) | Respiratory, Thoracic & Mediastinal Disorders(SOC) | Cough (PT) | Dyspnoea (PT) | Rhinitis Allergic (PT) | Skin & Subcutaneous Tissue Disorders (SOC) | Erythema (PT) | Nail Disorder (PT) | Rash Macular (PT) | Blood & Lymphatic System Disorders (SOC) | Febrile Neutropenia (PT) | Leukopenia (PT) | Gastrointestinal Disorders (SOC) | Diarrhoea (PT) | Stomatitis (PT) | Endocrine Disorders (SOC) | Thyroid Mass (PT) | Eye Disorders (SOC) | Retinal Detachment (PT) | Immune System Disorders (SOC) | Iodine Allergy (PT) | Investigations (SOC) | Aspartate Aminotransferase Increased (PT) | Renal & Urinary Disorders (SOC) | Dysuria (PT) | Reproductive System & Breast Disorders (SOC) | Breast Induration (PT) | Vascular Disorders (SOC) | Venous Thrombosis (PT) |
|---|
| Crossover From Placebo to Pertuzumab | 3 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Pertuzumab + Trastuzumab + Docetaxel | 17 | 9 | 5 | 2 | 1 | 0 | 0 | 1 | 0 | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 |
,| Placebo + Trastuzumab + Docetaxel | 18 | 8 | 6 | 0 | 0 | 1 | 1 | 0 | 1 | 3 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 2 | 1 | 1 | 0 | 0 | 2 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Laboratory Abnormalities in Blood Biochemistry Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period
Clinical laboratory tests for blood biochemistry parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to NCI-CTCAE v3.0. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks. ALP = alkaline phosphatase; GGT = gamma-glutamyl transferase; SGOT = serum glutamic-oxaloacetic transaminase; SGPT = serum glutamic-pyruvic transaminase (NCT00567190)
Timeframe: On Day 1 of every treatment cycle (1 cycle is 21 days) until Treatment Discontinuation Visit (see Description for time on study treatment per arm)
| Intervention | Participants (Count of Participants) |
|---|
| Albumin (g/L) - Low, Any Grade (Gr.) | Albumin (g/L) - Low, Gr. 1 | Albumin (g/L) - Low, Gr. 2 | Albumin (g/L) - Low, Gr. 3 | Albumin (g/L) - Low, Gr. 4 | ALP (U/L) - High, Any Gr. | ALP (U/L) - High, Gr. 1 | ALP (U/L) - High, Gr. 2 | ALP (U/L) - High, Gr. 3 | ALP (U/L) - High, Gr. 4 | Calcium (mmol/L) - Low, Any Gr. | Calcium (mmol/L) - Low, Gr. 1 | Calcium (mmol/L) - Low, Gr. 2 | Calcium (mmol/L) - Low, Gr. 3 | Calcium (mmol/L) - Low, Gr. 4 | Calcium (mmol/L) - High, Any Gr. | Calcium (mmol/L) - High, Gr. 1 | Calcium (mmol/L) - High, Gr. 2 | Calcium (mmol/L) - High, Gr. 3 | Calcium (mmol/L) - High, Gr. 4 | Creatinine (umol/L) - High, Any Gr. | Creatinine (umol/L) - High, Gr. 1 | Creatinine (umol/L) - High, Gr. 2 | Creatinine (umol/L) - High, Gr. 3 | Creatinine (umol/L) - High, Gr. 4 | Fasting Glucose (mmol/L) - Low, Any Gr. | Fasting Glucose (mmol/L) - Low, Gr. 1 | Fasting Glucose (mmol/L) - Low, Gr. 2 | Fasting Glucose (mmol/L) - Low, Gr. 3 | Fasting Glucose (mmol/L) - Low, Gr. 4 | Fasting Glucose (mmol/L) - High, Any Gr. | Fasting Glucose (mmol/L) - High, Gr. 1 | Fasting Glucose (mmol/L) - High, Gr. 2 | Fasting Glucose (mmol/L) - High, Gr. 3 | Fasting Glucose (mmol/L) - High, Gr. 4 | GGT (U/L) - High, Any Gr. | GGT (U/L) - High, Gr. 1 | GGT (U/L) - High, Gr. 2 | GGT (U/L) - High, Gr. 3 | GGT (U/L) - High, Gr. 4 | Magnesium (mmol/L) - Low, Any Gr. | Magnesium (mmol/L) - Low, Gr. 1 | Magnesium (mmol/L) - Low, Gr. 2 | Magnesium (mmol/L) - Low, Gr. 3 | Magnesium (mmol/L) - Low, Gr. 4 | Magnesium (mmol/L) - High, Any Gr. | Magnesium (mmol/L) - High, Gr. 1 | Magnesium (mmol/L) - High, Gr. 2 | Magnesium (mmol/L) - High, Gr. 3 | Magnesium (mmol/L) - High, Gr. 4 | Potassium (mmol/L) - Low, Any Gr. | Potassium (mmol/L) - Low, Gr. 1 | Potassium (mmol/L) - Low, Gr. 2 | Potassium (mmol/L) - Low, Gr. 3 | Potassium (mmol/L) - Low, Gr. 4 | Potassium (mmol/L) - High, Any Gr. | Potassium (mmol/L) - High, Gr. 1 | Potassium (mmol/L) - High, Gr. 2 | Potassium (mmol/L) - High, Gr. 3 | Potassium (mmol/L) - High, Gr. 4 | SGOT (U/L) - High, Any Gr. | SGOT (U/L) - High, Gr. 1 | SGOT (U/L) - High, Gr. 2 | SGOT (U/L) - High, Gr. 3 | SGOT (U/L) - High, Gr. 4 | SGPT (U/L) - High, Any Gr. | SGPT (U/L) - High, Gr. 1 | SGPT (U/L) - High, Gr. 2 | SGPT (U/L) - High, Gr. 3 | SGPT (U/L) - High, Gr. 4 | Sodium (mmol/L) - Low, Any Gr. | Sodium (mmol/L) - Low, Gr. 1 | Sodium (mmol/L) - Low, Gr. 2 | Sodium (mmol/L) - Low, Gr. 3 | Sodium (mmol/L) - Low, Gr. 4 | Sodium (mmol/L) - High, Any Gr. | Sodium (mmol/L) - High, Gr. 1 | Sodium (mmol/L) - High, Gr. 2 | Sodium (mmol/L) - High, Gr. 3 | Sodium (mmol/L) - High, Gr. 4 | Total Bilirubin (umol/L) - High, Any Gr. | Total Bilirubin (umol/L) - High, Gr. 1 | Total Bilirubin (umol/L) - High, Gr. 2 | Total Bilirubin (umol/L) - High, Gr. 3 | Total Bilirubin (umol/L) - High, Gr. 4 | Uric Acid (umol/L) - High, Any Gr. | Uric Acid (umol/L) - High, Gr. 1 | Uric Acid (umol/L) - High, Gr. 2 | Uric Acid (umol/L) - High, Gr. 3 | Uric Acid (umol/L) - High, Gr. 4 |
|---|
| Crossover From Placebo to Pertuzumab | 15 | 10 | 4 | 1 | 0 | 17 | 17 | 0 | 0 | 0 | 14 | 11 | 0 | 1 | 2 | 12 | 7 | 1 | 0 | 4 | 38 | 27 | 9 | 0 | 2 | 6 | 4 | 0 | 0 | 2 | 34 | 26 | 8 | 0 | 0 | 14 | 9 | 4 | 1 | 0 | 8 | 6 | 0 | 0 | 2 | 16 | 11 | 0 | 4 | 1 | 11 | 0 | 8 | 2 | 1 | 13 | 11 | 2 | 0 | 0 | 17 | 15 | 2 | 0 | 0 | 19 | 17 | 2 | 0 | 0 | 25 | 22 | 0 | 1 | 2 | 9 | 7 | 2 | 0 | 0 | 7 | 6 | 0 | 0 | 1 | 15 | 0 | 0 | 10 | 5 |
,| Pertuzumab + Trastuzumab + Docetaxel | 196 | 132 | 58 | 6 | 0 | 210 | 177 | 24 | 9 | 0 | 203 | 139 | 49 | 7 | 8 | 79 | 65 | 2 | 2 | 10 | 346 | 279 | 54 | 6 | 7 | 75 | 61 | 9 | 2 | 3 | 299 | 192 | 78 | 26 | 3 | 225 | 144 | 52 | 27 | 2 | 117 | 98 | 13 | 3 | 3 | 105 | 80 | 0 | 22 | 3 | 144 | 0 | 118 | 18 | 8 | 78 | 55 | 17 | 6 | 0 | 193 | 170 | 12 | 10 | 1 | 209 | 175 | 19 | 14 | 1 | 135 | 121 | 0 | 12 | 2 | 103 | 91 | 9 | 2 | 1 | 57 | 44 | 9 | 2 | 2 | 113 | 0 | 0 | 98 | 15 |
,| Placebo + Trastuzumab + Docetaxel | 163 | 113 | 46 | 4 | 0 | 184 | 158 | 19 | 7 | 0 | 156 | 107 | 45 | 3 | 1 | 54 | 50 | 0 | 3 | 1 | 317 | 271 | 44 | 2 | 0 | 42 | 32 | 9 | 1 | 0 | 271 | 168 | 83 | 20 | 0 | 209 | 133 | 41 | 30 | 5 | 79 | 71 | 7 | 1 | 0 | 76 | 58 | 0 | 18 | 0 | 80 | 0 | 68 | 10 | 2 | 67 | 49 | 15 | 3 | 0 | 184 | 169 | 11 | 4 | 0 | 195 | 172 | 18 | 5 | 0 | 109 | 87 | 0 | 21 | 1 | 76 | 71 | 4 | 1 | 0 | 35 | 26 | 7 | 2 | 0 | 118 | 0 | 0 | 116 | 2 |
Number of Participants With Laboratory Abnormalities in Hematology Tests by Highest Grade According to NCI-CTCAE v3.0 During the Treatment Period
Clinical laboratory tests for hematology parameters were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest grade according to NCI-CTCAE v3.0. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a change in concomitant therapy. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks. INR = International Normalized Ratio; PTT = partial thromboplastin time; WBC = white blood cell (NCT00567190)
Timeframe: On Day 1 (and Day 8 for some measures) of every treatment cycle (1 cycle is 21 days) until Treatment Discontinuation Visit (see Description for time on study treatment per arm)
| Intervention | Participants (Count of Participants) |
|---|
| Hemoglobin (g/L) - Low, Any Grade (Gr.) | Hemoglobin (g/L) - Low, Gr. 1 | Hemoglobin (g/L) - Low, Gr. 2 | Hemoglobin (g/L) - Low, Gr. 3 | Hemoglobin (g/L) - Low, Gr. 4 | Hemoglobin (g/L) - High, Any Gr. | Hemoglobin (g/L) - High, Gr. 1 | Hemoglobin (g/L) - High, Gr. 2 | Hemoglobin (g/L) - High, Gr. 3 | Hemoglobin (g/L) - High, Gr. 4 | Lymphocytes (10^9/L) - Low, Any Gr. | Lymphocytes (10^9/L) - Low, Gr. 1 | Lymphocytes (10^9/L) - Low, Gr. 2 | Lymphocytes (10^9/L) - Low, Gr. 3 | Lymphocytes (10^9/L) - Low, Gr. 4 | Lymphocytes (10^9/L)- High, Any Gr. | Lymphocytes (10^9/L)- High, Gr. 1 | Lymphocytes (10^9/L)- High, Gr. 2 | Lymphocytes (10^9/L)- High, Gr. 3 | Lymphocytes (10^9/L)- High, Gr. 4 | Neutrophils (10^9/L)- Low, Any Gr. | Neutrophils (10^9/L)- Low, Gr. 1 | Neutrophils (10^9/L)- Low, Gr. 2 | Neutrophils (10^9/L)- Low, Gr. 3 | Neutrophils (10^9/L)- Low, Gr. 4 | PTT (sec) - High, Any Gr. | PTT (sec) - High, Gr. 1 | PTT (sec) - High, Gr. 2 | PTT (sec) - High, Gr. 3 | PTT (sec) - High, Gr. 4 | Platelets (10^9/L) - Low, Any Gr. | Platelets (10^9/L) - Low, Gr. 1 | Platelets (10^9/L) - Low, Gr. 2 | Platelets (10^9/L) - Low, Gr. 3 | Platelets (10^9/L) - Low, Gr. 4 | Prothrombin Time (INR) - High, Any Gr. | Prothrombin Time (INR) - High, Gr. 1 | Prothrombin Time (INR) - High, Gr. 2 | Prothrombin Time (INR) - High, Gr. 3 | Prothrombin Time (INR) - High, Gr. 4 | WBC (10^9/L) - Low, Any Gr. | WBC (10^9/L) - Low, Gr. 1 | WBC (10^9/L) - Low, Gr. 2 | WBC (10^9/L) - Low, Gr. 3 | WBC (10^9/L) - Low, Gr. 4 | WBC (10^9/L) - High, Any Gr. | WBC (10^9/L) - High, Gr. 1 | WBC (10^9/L) - High, Gr. 2 | WBC (10^9/L) - High, Gr. 3 | WBC (10^9/L) - High, Gr. 4 |
|---|
| Crossover From Placebo to Pertuzumab | 20 | 9 | 6 | 5 | 0 | 4 | 2 | 0 | 2 | 0 | 8 | 0 | 4 | 3 | 1 | 9 | 0 | 6 | 3 | 0 | 2 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 13 | 11 | 0 | 0 | 2 | 11 | 9 | 0 | 2 | 0 | 5 | 1 | 3 | 0 | 1 | 1 | 0 | 0 | 1 | 0 |
,| Pertuzumab + Trastuzumab + Docetaxel | 372 | 186 | 161 | 25 | 0 | 23 | 20 | 2 | 1 | 0 | 276 | 39 | 136 | 69 | 32 | 72 | 0 | 57 | 15 | 0 | 371 | 4 | 34 | 99 | 234 | 9 | 2 | 4 | 3 | 0 | 92 | 78 | 5 | 3 | 6 | 157 | 136 | 6 | 15 | 0 | 387 | 34 | 92 | 206 | 55 | 3 | 0 | 0 | 3 | 0 |
,| Placebo + Trastuzumab + Docetaxel | 350 | 202 | 127 | 21 | 0 | 10 | 9 | 1 | 0 | 0 | 259 | 36 | 128 | 64 | 31 | 58 | 0 | 49 | 9 | 0 | 349 | 7 | 25 | 81 | 236 | 6 | 5 | 0 | 1 | 0 | 82 | 75 | 5 | 2 | 0 | 135 | 127 | 3 | 5 | 0 | 366 | 36 | 92 | 186 | 52 | 0 | 0 | 0 | 0 | 0 |
Objective Response Determined by an Independent Review Facility
An objective response was defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR) determined by an independent review facility (IRF) using RECIST v1.0 on two consecutive occasions ≥4 weeks apart. For target lesions, CR: disappearance of all target lesions; PR: ≥30% decrease in the sum of the longest diameter (LD) of target lesions (baseline sum LD as reference); PD: ≥20% increase in the sum of the LD of target lesions (smallest sum of the LD recorded as reference) or appearance of ≥1 new lesion; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase for PD. For non-target lesions, CR: disappearance of all non-target lesions; Incomplete/SD: persistence of ≥1 non-target lesions; PD: unequivocal progression of existing non-target lesions. 95% confidence intervals (CI) were calculated only for clinical responses using the Pearson-Clopper method. (NCT00567190)
Timeframe: Tumor assessments every 9 weeks from Baseline until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months)
| Intervention | Percentage of patients (Number) |
|---|
| Objective Response (CR + PR) | Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Unable to Assess (UA) | Missing (No Assessment) |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 80.2 | 5.5 | 74.6 | 14.6 | 3.8 | 0.6 | 0.9 |
,| Placebo + Trastuzumab + Docetaxel | 69.3 | 4.2 | 65.2 | 20.8 | 8.3 | 0.6 | 0.9 |
Overall Number of Adverse Events by Severity (NCI-CTCAE v3.0 All Grades and Grades 3 to 5) Per 100 Patient-Years of Exposure During the Treatment Period
Adverse event (AE) severity, including serious and non-serious AEs, was assessed according to the NCI-CTCAE version 3.0; if the AE was not specifically listed, the following grades of severity were used: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe; Grade 4 is life-threatening or disabling; and Grade 5 is death. Multiple occurrences of the same AE in 1 participant were counted multiple times. Only AEs that started during the overall study treatment period were included. The cutoff date for inclusion of events and for calculation of patient-years was the date of the most recent follow-up of the participant, defined as the last available date during the treatment period, excluding pre-treatment and safety follow-up data. Confidence intervals were calculated assuming the number of events followed a Poisson distribution. Data reported prior to the date of first crossover treatment were included under the Placebo arm for participants who crossed over from placebo to pertuzumab. (NCT00567190)
Timeframe: From Baseline to 42 days after the last dose of study treatment (total patient-years of exposure on study treatment in Placebo vs. Pertuzumab arms: 526.81 vs. 989.88 patient-years)
| Intervention | Events per 100 patient-years (Number) |
|---|
| All Grades | Grades 3 to 5 |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 1203.0 | 131.7 |
,| Placebo + Trastuzumab + Docetaxel | 1720.2 | 225.3 |
Overall Number of Participants Who Experienced at Least One Adverse Event Leading to Discontinuation of Any or All Study Medication
Participants could continue study treatment with pertuzumab/placebo plus trastuzumab when docetaxel was discontinued due to an adverse event (AE). Discontinuation of pertuzumab/placebo or trastuzumab due to an AE led to discontinuation of all study medication. The number of participants who discontinued any study medication due to an AE includes those who discontinued all study medication and those who discontinued docetaxel only and then continued on targeted therapy (note: some of these participants may have subsequently discontinued all treatment due to a separate AE). Multiple occurrences of the same adverse event in 1 participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for those who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks. (NCT00567190)
Timeframe: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
| Intervention | Participants (Count of Participants) |
|---|
| AE Leading to Discontinuation-Any Study Medication | AE Leading to Discontinuation-All Study Medication |
|---|
| Crossover From Placebo to Pertuzumab | 5 | 4 |
,| Pertuzumab + Trastuzumab + Docetaxel | 131 | 39 |
,| Placebo + Trastuzumab + Docetaxel | 114 | 24 |
Duration of Objective Response Determined by an Independent Review Facility
Duration of objective response (estimated using the Kaplan-Meier method) was defined as the time from the initial confirmed complete response (CR) or partial response (PR), the date of tumor assessment at which the CR/PR was first detected by the independent review facility (IRF) using RECIST version 1.0, until the date of IRF-determined progressive disease (PD), death from any cause within 18 weeks of the last tumor assessment, or first administration of next line of anti-cancer therapy (whichever occurred first). If the visit when the initial CR or PR was observed spanned multiple dates, the latest date was used. Only participants in the ITT analysis population with an IRF-determined objective response (CR or PR), observed prior to IRF-assessed PD, death or next line of anti-cancer therapy, were included in the analysis. Participants who did not progress or die after they had a confirmed response were censored at the date of their last IRF-evaluable tumor measurement. (NCT00567190)
Timeframe: From initial IRF-confirmed objective response until IRF-determined progressive disease (PD), death, or first administration of next line of anti-cancer therapy (whichever occurred first), up to the primary completion date (up to 3 years, 3 months)
| Intervention | Weeks (Median) |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 87.6 |
| Placebo + Trastuzumab + Docetaxel | 54.1 |
Overall Number of Participants Who Experienced at Least One Adverse Event That Resulted in Interruption or Modification of Any Study Medication
Pertuzumab, trastuzumab, and docetaxel administration could have been delayed to assess or treat adverse events (AEs). Docetaxel dose reduction was allowed for myelosuppression, hepatic dysfunction, and other toxicities. No dose reduction was allowed for pertuzumab or trastuzumab. Multiple occurrences of the same adverse event in one participant was counted only once. AEs reported prior to first crossover treatment were included in the Placebo arm, and after that date in the Crossover arm, for participants who crossed over from placebo to pertuzumab. Median [range] time on study treatment per arm: Placebo: 49.3 [0.3-514.7] weeks; Pertuzumab: 75.7 [0.6-519.6] weeks; Crossover: 129.9 [0.3-322.3] weeks (NCT00567190)
Timeframe: Placebo arm: Baseline to last dose of study treatment +42 days (or crossover date); Pertuzumab arm: Baseline to last dose of study treatment +42 days; Crossover arm: Crossover date to last dose of study treatment +42 days (see Description - time per arm)
| Intervention | Participants (Count of Participants) |
|---|
| Placebo + Trastuzumab + Docetaxel | 217 |
| Pertuzumab + Trastuzumab + Docetaxel | 265 |
| Crossover From Placebo to Pertuzumab | 16 |
Progression-Free Survival (PFS) Determined by an Independent Review Facility
PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by an independent review facility (IRF) using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of ≥1 new lesion. For non-target lesions, PD was defined as the appearance of ≥1 new lesion or unequivocal progression of existing lesions. Participants without IRF-determined PD or who had not died within 18 weeks of their last IRF-determined, progression-free tumor assessment were censored at the date of the last IRF-reviewed, evaluable tumor assessment; those with no post-baseline tumor assessment and who had not died within 18 weeks of baseline were censored at 1 day. (NCT00567190)
Timeframe: Tumor assessments every 9 weeks from randomization to IRF-determined PD or death from any cause, whichever occurred first, up to the primary completion date (up to 3 years, 3 months)
| Intervention | Months (Median) |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 18.5 |
| Placebo + Trastuzumab + Docetaxel | 12.4 |
Progression-Free Survival (PFS) Determined by the Investigator
PFS was defined as the time from randomization to first documented radiographical progressive disease (PD), as determined by the investigator using RECIST version 1.0, or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first (Kaplan-Meier method). For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum of the LD recorded since treatment started or the appearance of ≥1 new lesion. For non-target lesions, PD was defined as the appearance of ≥1 new lesion or unequivocal progression of existing lesions. Participants without PD or who had not died within 18 weeks of their last investigator-determined, progression-free tumor assessment were censored at the date of the last investigator tumor assessment; those with no post-baseline tumor assessment and who had not died within 18 weeks of baseline were censored at 1 day. (NCT00567190)
Timeframe: Tumor assessments every 9 weeks from randomization to investigator-determined PD or death from any cause, whichever occurred first (median [range] time on study in pertuzumab vs. placebo arms: 201.8 [0.7-520.0] weeks vs. 138.0 [0.4-514.7] weeks)
| Intervention | Months (Median) |
|---|
| Pertuzumab + Trastuzumab + Docetaxel | 18.7 |
| Placebo + Trastuzumab + Docetaxel | 12.4 |
Objective Tumor Response
"Response is measured according to Response Evaluation Criteria in Solid Tumors Criteria (RECIST v 1.0):~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.~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.~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.~Stable Disease is any condition not meeting the above criteria.~Indeterminate is defined as having no repeat tumor assessments following initiation of study therapy6" (NCT00569673)
Timeframe: every other cycle for the first 6 months; then every 3 months thereafter (up to 5 years)
| Intervention | participants (Number) |
|---|
| Partial response | Stable disease | Disease progression | Indeterminate |
|---|
| Docetaxel Plus Trabectedin | 21 | 32 | 17 | 1 |
Number of Participants With Adverse Effects (Grade 3 or Higher) as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
(NCT00569673)
Timeframe: Prior to each cycle and 30 days after the last cycle (average of 5 months)
| Intervention | Participants (Count of Participants) |
|---|
| Leukopenia | Thrombocytopenia | Neutropenia | Anemia | Other hematologic | Constitutional | Nausea | Vomiting | Gastrointestinal | Hemorrhage | Infection | Metabolic | Musculoskeletal | Other neurological | Pain | Pulmonary |
|---|
| Docetaxel Plus Trabectedin | 21 | 7 | 21 | 5 | 2 | 8 | 6 | 7 | 11 | 1 | 10 | 10 | 3 | 2 | 6 | 2 |
Percentage of Participants Undergoing Breast-Conserving Surgery
The percentage of participants who were able to undergo breast-conserving surgical procedures (segmentectomy plus lymphadenectomy or quadrantectomy plus lymphadenectomy) rather than non-breast conserving procedures (radical mastectomy or modified-radical mastectomy) following 4 or more treatment cycles. (NCT00576901)
Timeframe: Following Cycle 6
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab+Docetaxel+Capecitabine | 26.09 |
Percentage of Participants Achieving Pathological Complete Response (pCR)
pCR was defined as the absence of viable tumor cells, as determined by standard histologic procedure, in the tumor specimen (including regional lymph nodes) obtained at surgery. In order to minimize evaluation bias, tumor specimens were analyzed by both a central and local pathologist. The number of participants with pathological tumor stage 0 (pT0) and regional lymph nodes stage 0 (pN0) at surgery was determined. pCR was defined as the number of participants with pT0 and pN0 at surgery divided by the total number of participants with pathological tumor stage data collected. (NCT00576901)
Timeframe: At time of surgery, after receiving up to 6 cycles of treatment (average of 12 to 18 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab+Docetaxel+Capecitabine | 0 |
Percentage of Participants Achieving an Overall Response of Complete Response (CR) or Partial Response (PR)
The percentage of participants with a best overall response of CR or PR according to Response Evaluation Criteria in Solid Tumors (RECIST). 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 have decreased to normal (short axis less than [<]10 millimeters [mm]). No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) decrease under baseline of the sum of diameters of all target lesions. The short aixs 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. (NCT00576901)
Timeframe: Day 1 of Cycles 1-6
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab+Docetaxel+Capecitabine | 80 |
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
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) | Maintained Continued CR | Partial Response (PR) | No Response | Not Evaluable |
|---|
| Bevacizumab + High-Dose Chemotherapy | 33.3 | 42.0 | 8.3 | 8.3 | 8.3 |
The Effects of Testosterone Administration on Docetaxel Pharmacokinetics.
Docetaxel Pharmacokinetic parameters for cycles 1 and 2. (NCT00587431)
Timeframe: at Cycle 1 and 2
| Intervention | L/hr (Mean) |
|---|
| Docetaxel clearance (Cycle 1) | Docetaxel clearance (Cycle 2) |
|---|
| All Participants | 23.9 | 23.6 |
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
| Intervention | months (Median) |
|---|
| Chemotherapy Arm (Arm A) | 4.3 |
| Chemotherapy+Bevacizumab (Arm B) | 6.0 |
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
| Intervention | months (Median) |
|---|
| Chemotherapy Arm (Arm A) | 11.0 |
| Chemotherapy+Bevacizumab (Arm B) | 12.6 |
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
| Intervention | proportion of participants (Number) |
|---|
| Chemotherapy Arm (Arm A) | 0.245 |
| Chemotherapy+Bevacizumab (Arm B) | 0.355 |
Prostate Specific Antigen (PSA) Response Rate
"PSA Response: ≥50% decline from baseline PSA measurement confirmed by a second PSA measurement 3 weeks later. Patients may not demonstrate clinical or radiographic evidence of disease progression.~PSA progression (PSA-P): Two measurements of rising serum PSA measured at least 2 weeks apart where the second is greater than the first." (NCT00589420)
Timeframe: From start of treatment until withdrawal from the study, approximately 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase II Trial of Sorafenib and Docetaxel | 6 |
6-month Progression-free Survival (PFS)
Number of patients that achieved 6 month PFS (NCT00589420)
Timeframe: 6 months from end of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Phase II Trial of Sorafenib and Docetaxel | 10 |
Objective Response Rate (ORR)
To determine the ORR in patients with measurable disease (NCT00589420)
Timeframe: 6 months from end of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Phase II Trial of Sorafenib and Docetaxel | 3 |
Efficacy Measured by Response Rate in Participants
"Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT and 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 (NR/SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since the treatment started;~Progressive Disease (PD), A 20% or greater increase in the sum of the longest diameter of measured lesions (target lesions), taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions." (NCT00591149)
Timeframe: 12 Weeks, 1 Year
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Not Evaluable |
|---|
| Oxaliplatin and Docetaxel | 0 | 2 | 6 | 3 | 5 |
Percent of Patients Surviving at Annual Intervals
(NCT00609336)
Timeframe: 5 years
| Intervention | percentage of participants (Number) |
|---|
| Year 1 | Year 2 | Year 3 | Year 4 | Year 5 |
|---|
| Treatment (Chemotherapy, Radiation, Pancreaticoduodenectomy) | 81 | 62 | 45 | 37 | 31 |
Surgical Completion Rate and Complication Rate
(NCT00609336)
Timeframe: Up to 6 weeks following the completion of chemoradiotherapy
| Intervention | Participants (Count of Participants) |
|---|
| Completion rate | Complication rate |
|---|
| Treatment (Chemotherapy, Radiation, Pancreaticoduodenectomy) | 22 | 2 |
Frequency and Severity of Toxicities Associated With This Treatment Regimen as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
(NCT00609336)
Timeframe: Up to 26 weeks after surgery (the end of adjuvant chemotherapy)
| Intervention | occurrence of toxicities (Number) |
|---|
| Any Grade 2 CTCAE toxicity | Any Grade 3 CTCAE toxicity | Any Grade 4 CTCAE toxicity |
|---|
| Treatment (Chemotherapy, Radiation, Pancreaticoduodenectomy) | 21 | 121 | 14 |
Percent of Patients Surviving at 5 Years
Kaplan-Meier estimate of overall survival at 5 years (NCT00609336)
Timeframe: Up to 5 years
| Intervention | percentage of eligible pts alive (Number) |
|---|
| Treatment (Chemotherapy, Radiation, Pancreaticoduodenectomy) | 31.6 |
Pathologic Response Rate (Complete, Near-complete, Partial) to Neoadjuvant Chemotherapy and Chemoradiotherapy
The resected pancreaticoduodenectomy specimen and accompanying lymph nodes will be staged according to American Joint Committee on Cancer 6th Edition incorporating the prefix y to indicate a specimen status-post neoadjuvant treatment (ypTNM). Cancer 2012;118:1382-90 (NCT00609336)
Timeframe: Up to 7 years
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Chemotherapy, Radiation, Pancreaticoduodenectomy) | 20 |
Overall Survival
Median time (in months) from randomisation until death using the Kaplan-Meier method. (NCT00617669)
Timeframe: Patients were followed for survival up to 40 months
| Intervention | Months (Median) |
|---|
| ZD4054 + Docetaxel | 20.0 |
| Placebo + Docetaxel | 19.2 |
Pain Response
Number of patients with a pain response, defined as a decrease in brief pain inventory questionnaire (BPI) of at least 2 points from baseline or a decrease in opiate use of 25% from baseline. (NCT00617669)
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
| Intervention | Participants (Number) |
|---|
| ZD4054 + Docetaxel | 255 |
| Placebo + Docetaxel | 276 |
Progression Free Survival
Median time (in months) from randomisation until clinical progression of disease using the Kaplan-Meier method. Progression is defined, using RECIST, as a measurable increase in the smallest dimension of any target or non-target lesion, or the appearance of new lesions, since baseline (NCT00617669)
Timeframe: Patients were followed for progression up to 40 months
| Intervention | Months (Median) |
|---|
| ZD4054 + Docetaxel | 7.0 |
| Placebo + Docetaxel | 7.9 |
PSA Response
PSA response defined as >50% decrease in serum PSA values from baseline seen in at least 2 consecutive PSA values at least 2 weeks apart. (NCT00617669)
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
| Intervention | Participants (Number) |
|---|
| ZD4054 + Docetaxel | 279 |
| Placebo + Docetaxel | 298 |
Time to Pain Progression
Median time (in months) from randomisation until date of first assessment of increased pain using the Kaplan-Meier method, where increased pain event is defined as the first of a patient requiring opiate medication for duration of ≥1 week for pain due to prostate cancer metastasis, pain due to metastasis that has an increase in the worst pain item of the Brief Pain Inventory (BPI) from baseline to a minimum score of 5 with no decrease in analgesic use, or pain due to metastasis requiring radionuclide therapy, radiation therapy or surgery. (NCT00617669)
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
| Intervention | Months (Median) |
|---|
| ZD4054 + Docetaxel | 9.3 |
| Placebo + Docetaxel | 10.0 |
Time to Prostate-specific Antigen (PSA) Progression
Median time (in months) from randomisation until first PSA value >50% higher than baseline of at least 5ng/ml seen in at least 2 consecutive PSA values at least 2 weeks apart using the Kaplan-Meier method. (NCT00617669)
Timeframe: While receiving docetaxel study visits were aligned with its administration ie every 3weeks, after 12 weeks and completion of docetaxel therapy every 12 weeks (up to 40 months)
| Intervention | Months (Median) |
|---|
| ZD4054 + Docetaxel | 11.9 |
| Placebo + Docetaxel | 12.1 |
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
| Intervention | months (Median) |
|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | NA |
| Docetaxel and Carboplatin | 55.1 |
Safety
Adverse Events occuring in >15% of patients (NCT00621049)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Fatigue | Nausea | Diarrhea | Anemia | Neutrophil count decreased | White blood cell decreased | Alopecia | Pain | Platelet count decreased | Constipation | Dyspnea | Anorexia | Hyperglycemia | Dysgeusia | Mucositis | Vomiting | Cough | Peripheral sensory neuropathy |
|---|
| Docetaxel and Carboplatin | 41 | 36 | 24 | 28 | 26 | 27 | 21 | 15 | 20 | 18 | 17 | 18 | 11 | 14 | 12 | 13 | 8 | 2 |
,| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | 37 | 32 | 26 | 18 | 20 | 18 | 21 | 23 | 13 | 14 | 14 | 12 | 18 | 12 | 12 | 10 | 12 | 15 |
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
| Intervention | months (Median) |
|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | NA |
| Docetaxel and Carboplatin | NA |
2-year Survival
Proportion of patients known to still be alive 2 years after coming on study (NCT00621049)
Timeframe: 24 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel/Carboplatin/Bevacizumab/Erlotinib | 78.2 |
| Docetaxel and Carboplatin | 71.9 |
Number of Disease-free Survival Events for Triple-negative Subgroup
DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with triple negative breast cancer only. (NCT00630032)
Timeframe: At 5 years
| Intervention | Events (Number) |
|---|
| Docetaxel | 69 |
| Ixabepilone | 50 |
Number of Event-free Survival
The Event-free Survival is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or the date of second neoplasia, or the date of death from any cause, whichever occurs first. (NCT00630032)
Timeframe: At 5 years
| Intervention | Events (Number) |
|---|
| Docetaxel | 77.46 |
| Ixabepilone | 81.53 |
Overall Survival
The overall survival is the length of time from randomization that patients enrolled in the study are still alive. (NCT00630032)
Timeframe: At 5 years
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel | 87.00 |
| Ixabepilone | 87.60 |
Number of Disease-free Survival Events for ER+/PR-/HER2- Subgroup
DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first in participants with ER+/PR-/HER2- breast cancer only. (NCT00630032)
Timeframe: At 5 years
| Intervention | Events (Number) |
|---|
| Docetaxel | 21 |
| Ixabepilone | 17 |
Percentage of Participants With Disease-free Survival (DFS)
DFS is defined as the interval between the date of randomization and the date of breast cancer relapse (local, regional or distant) or the date of invasive contralateral breast cancer or death from any cause, whichever occurs first (NCT00630032)
Timeframe: At 5 years
| Intervention | Percentage of participants (Number) |
|---|
| Docetaxel | 78.97 |
| Ixabepilone | 83.37 |
Pathologic Complete Response (pCR) Rate in Patients With HER2-negative Early-stage Breast Cancer
Pathological complete response (pCR) was defined as the disappearance of all invasive disease in the breast or if only residual in situ or lymph node disease is found. The pCR rate is presented with its 95% confidence interval for the Guided and Non-guided arms. (NCT00636441)
Timeframe: 4-5 weeks after the fourth cycle of chemotherapy; approximately 16-17 weeks
| Intervention | percentage of participants (Number) |
|---|
| Guided Arm | 16.7 |
| Non-Guided Arm | 9.1 |
Disease-free Survival
Disease-free survival is defined as the length of time from enrollment to local or distant disease recurrence, whichever comes first; disease-free deaths are censored. The 2-year disease-free survival rate is estimated with its 95% confidence interval. (NCT00636441)
Timeframe: 2 years
| Intervention | estimated % of participants disease-free (Number) |
|---|
| Guided Arm | 92 |
| Non-Guided Arm | 89 |
Sites of Recurrence
Sites of Recurrence is a categorical outcome whose possible values are the organ-specific sites at which disease recurrence was observed. A patient may recur at more than one site. (NCT00636441)
Timeframe: 10 years
| Intervention | participants (Number) |
|---|
| Bone | Brain | Chest Wall | Liver | Lung |
|---|
| Guided Arm | 3 | 1 | 1 | 2 | 1 |
,| Non-Guided Arm | 1 | 0 | 0 | 0 | 0 |
Clinical Response Using WHO Criteria
"WHO criteria are based on the sum of the products of the longest axis and the longest perpendicular axis. Bi-dimensional measurements were taken of all breast lesions and axillary nodes using the best imaging modality performed after completion of assigned therapy.~Clinical Complete Response (cCR): Disappearance of all target lesions by physical exam and best imaging modality.~Clinical Partial Response (cPR): 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 increase to qualify for PD taking as references the sum LD at treatment initiation. Patients having a documented response with no reconfirmation of the response will be listed with stable disease.~Progression (PD): At least a 20% increase in the sum of the LD of target lesions or the appearance of one or more new lesion." (NCT00636441)
Timeframe: 12 weeks, 2-3 weeks after the fourth cycle of chemotherapy
| Intervention | participants (Number) |
|---|
| Complete Response (cCR) | Partial Response (cPR) | Stable Disease | Progressive Disease | Not Evaluable/Not Assessed |
|---|
| Guided Arm | 2 | 15 | 6 | 1 | 1 |
,| Non-Guided Arm | 2 | 7 | 2 | 0 | 2 |
To Percentage of Patients Who Had Breast-conserving Surgery at First Attempt.
The percentage of patients who had breast-conserving surgery at first attempt, measured only in patients with T2 tumors classified as potential candidates for breast conservation. (NCT00636441)
Timeframe: 6 months
| Intervention | percentage of T2 tumor patients (Number) |
|---|
| Guided Arm | 67 |
| Non-Guided Arm | 100 |
Overall Survival
Overall survival is defined as the time from enrollment to death due to any cause. The 2-year overall survival rate is estimated with the Kaplan-Meier method. (NCT00636441)
Timeframe: 2 years
| Intervention | Estimated % of participants surviving (Number) |
|---|
| Guided Arm | 96 |
| Non-Guided Arm | 100 |
Estimate Overall Survival
Overall survival is defined as the time from date of first treatment to the date of death due to any cause. For participants who were alive, overall survival was censored at their last contact. Participants were still followed for overall survival after they stopped receiving study drug. (NCT00642018)
Timeframe: First treatment to death due to any cause up to 45.54 months
| Intervention | months (Median) |
|---|
| Docetaxel | 29.04 |
| LY2181308 + Docetaxel | 27.04 |
Percentage of Participants With Complete Response or Partial Response (Overall Response Rate)
Overall response rate was defined as the percentage of participants who achieved a complete response (CR) or partial response (PR) per the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions. Objective 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. (NCT00642018)
Timeframe: Baseline to measured progressive disease up to 41.00 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel | 21.6 |
| LY2181308 + Docetaxel | 10.2 |
Prostate Specific Antigen (PSA) Kinetics: Percentage of Participants With PSA Response (Response Rate)
PSA response was defined as a post-baseline PSA level decline of at least 50% relative to the baseline value. Response rate calculated as 100*n/N where n=the number of participants with responses and N=the total number of participants treated. (NCT00642018)
Timeframe: Baseline, 18 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel | 56.9 |
| LY2181308 + Docetaxel | 56.1 |
Number of Participants Who Died Due to Progressive Disease During the 30 Days Following Discontinuation From Study Treatment
(NCT00642018)
Timeframe: Study treatment discontinuation up to 30 days post study treatment discontinuation
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel | 1 |
| LY2181308 + Docetaxel | 0 |
Change From Baseline to Day 21 in Granulocyte Colony Stimulating Factor(G-CSF) (Assess Biomarker Responses)
G-CSF [international units per milliliter (IU/mL)] was used to estimate biomarker responses and is presented as the percentage change from baseline. (NCT00642018)
Timeframe: Baseline, 21 days
| Intervention | percentage change (Number) |
|---|
| Docetaxel | -32.5 |
| LY2181308 | 233.3 |
Number of Participants With Adverse Events (Safety)
Data are presented as number of participants who experienced serious adverse events or all other nonserious adverse events during the study including the 30-day follow-up period. A summary of serious adverse events and other nonserious adverse events is located in the Reported Adverse Event section. The participants received maximum 24 cycles of treatment (1cycle = 3 weeks). Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 19 months. (NCT00642018)
Timeframe: First treatment dose up to 19 months
| Intervention | Participants (Count of Participants) |
|---|
| Serious Adverse Events | Other Nonserious Adverse Events |
|---|
| Docetaxel | 11 | 50 |
,| LY2181308 + Docetaxel | 47 | 94 |
Functional Assessment of Cancer Therapy-General (FACT-G) Total Score at 3 Months (Evaluate Clinical Symptoms)
The total FACT-G is the sum of 4 subscale scores on the FACT-Prostate Cancer (FACT-P) participant-rated questionnaire representing general cancer symptoms: physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), and functional well-being (7 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-G score ranges from 0-108, with higher scores representing a better quality of life with fewer symptoms. (NCT00642018)
Timeframe: 3 months
| Intervention | units on a scale (Median) |
|---|
| Docetaxel | 84 |
| LY2181308 + Docetaxel | 80 |
Adverse Event Profile
Data presented are the number of participants with all treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), discontinuations due to SAEs and AEs, and deaths that occurred in this study that were assessed by investigators as possibly related to study drug. The participants received maximum 24 cycles of treatment (1cycle = 3 weeks). Safety data were collected up to 24 cycles plus 30 days of follow-up for a total up to 19 months. (NCT00642018)
Timeframe: First treatment dose up to 19 months
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | SAEs | Discontinuations due to AEs | Discontinuations due to SAEs | Death |
|---|
| Docetaxel | 45 | 5 | 6 | 1 | 0 |
,| LY2181308 + Docetaxel | 91 | 27 | 22 | 3 | 0 |
Progression-free Survival (PFS) in Participants With Hormone Refractory Prostate Cancer (HRPC) Administered LY2181308 Sodium Plus Docetaxel Compared to Docetaxel Alone
PFS is defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using the Response Evaluation Criteria In Solid Tumors (RECIST) criteria. PD is ≥20% increase in sum of longest diameter of target lesions and/or a new lesion. For participants who had no PD or death, PFS was censored at their last contact. Participants were still followed for PFS after they stopped receiving study drug. (NCT00642018)
Timeframe: Baseline to measured progressive disease or death due to any cause up to 44.68 months
| Intervention | months (Median) |
|---|
| Docetaxel | 9.00 |
| LY2181308 + Docetaxel | 8.64 |
Estimate Duration of Overall Response
The duration of response [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. CR or PR is classified by the investigators 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. For participants who had no progression or death, the duration of response was censored at their last contact. (NCT00642018)
Timeframe: Time of response to time of measured progressive disease up to 41.00 months
| Intervention | months (Median) |
|---|
| Docetaxel | 10.81 |
| LY2181308 + Docetaxel | 9.66 |
Functional Assessment of Cancer Therapy-Prostate Cancer (FACT-P) Total Score at 3 Months (Participant Reported Outcomes)
The FACT-P is a 39-item participant-rated questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better quality of life with fewer symptoms. (NCT00642018)
Timeframe: 3 months
| Intervention | units on a scale (Median) |
|---|
| Docetaxel | 117 |
| LY2181308 + Docetaxel | 115 |
Pharmacokinetics of Docetaxel: Area Under the Concentration Time Curve From Time Zero to Infinity (AUC0-infinity)
(NCT00642018)
Timeframe: Predose up to 8 hours postdose in Cycle 1
| Intervention | nanograms*hour per milliliter (ng*h/mL) (Geometric Mean) |
|---|
| Docetaxel | 825 |
| LY2181308 + Docetaxel | 799 |
Dose Limiting Toxicity (DLT)
"The number of DLTs experienced by participants within the first 21 days.~DLTs were defined as toxicities possibly, probably, or definitely related to the study drug observed during the first 2 cycles (first 42 days) as follows:~Non-hematologic toxicity Grade ≥3 by the NCI CTCAE version 3.0.~ANC<1000 for more than 7 days despite use of pegfilgrastim.~Platelet count <25,000 for more than 7 days, or associated with bleeding, or less than 10,000 at any time." (NCT00645333)
Timeframe: first 21 days
| Intervention | Dose Limiting Toxicities (Number) |
|---|
| MK-0752 and Docetaxel | 5 |
Maximum Tolerated Dose (MTD)
The Maximum Tolerated Dose (MTD) for MK-0752 will be determined. Dose levels were: Level 1: 300 mg MK-0752 by mouth days 1-3; Level 2: 450 mg MK-0752 by mouth days 1-3; Level 3: 600 mg MK-0752 by mouth days 1-3; Level 4: 800 mg MK-0752 by mouth days 1-3. (NCT00645333)
Timeframe: Up to 3 years
| Intervention | mg (Number) |
|---|
| MK-0752 and Docetaxel | 600 |
Proportion of Patients With PSA Responses at One Year After the Completion of ADT
The PSA response was defined using two cut-offs: PSA <0.2 ng/mL or PSA <0.01 ng/mL at the one year after completion of ADT. (NCT00658697)
Timeframe: 1 year + 3 month off last ADT injection
| Intervention | percentage of participants with data (Number) |
|---|
| PSA <0.2 ng/mL | PSA <=0.01 ng/mL |
|---|
| Docetaxel, Bevacizumab, and ADT | 44 | 25 |
Time to PSA Progression (TTP)
For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA > 0.2 ng/mL. For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA > 2.0 ng/mL. Any new site of metastatic disease on imagining would be considered progression regardless of PSA value (NCT00658697)
Timeframe: participants were followed for the duration of the study, an average of 2 years
| Intervention | months (Median) |
|---|
| Docetaxel, Bevacizumab, and ADT | 27.5 |
Prostate-Specific Antigen (PSA) Progression at 1 Year After Completing Androgen Deprivation Therapy (ADT)
"For prostatectomy patients: at least two serial rising PSA from treatment nadir and PSA > 0.2 ng/mL.~For patient receiving radiation therapy alone as primary local therapy, at least two serial rising PSA from treatment nadir and PSA >2.0 ng/mL.~Any new site of metastatic disease on imagining would be considered progression regardless of PSA value Clinical assessments (Vitals, Physical Exam, Performance Status, PSA and testosterone) were performed every 3 months starting at completion of hormone therapy until PSA progression." (NCT00658697)
Timeframe: participants were followed for the duration of the study, an average of 2 years
| Intervention | percentage of participants with data (Number) |
|---|
| Docetaxel, Bevacizumab, and ADT | 98 |
Toxicity
Treatment related adverse events were graded based on CTCAE v. 3.0. (NCT00658697)
Timeframe: Assessed each cycle throughout treatment form time of first dose to 30 days post-treatment, up to 2 years
| Intervention | participants (Number) |
|---|
| Grade 3 treatment related AE | Grade 4 treatment related AEs |
|---|
| Docetaxel, Bevacizumab, and ADT | 16 | 5 |
Testosterone Recovery
Testosterone recovery was defined as >100 or within DFCI institute normal range (240-950) at one year after the completion of ADT (NCT00658697)
Timeframe: 2 years
| Intervention | percentage of participants with data (Number) |
|---|
| Testosterone >=100 ng/mL | Testosterone >=240 ng/mL |
|---|
| Docetaxel, Bevacizumab, and ADT | 83 | 35 |
Neurotoxicity Assessment at Baseline
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline (prior to chemotherapy treatment) and the mean total score for all patients is reported. (NCT00659269)
Timeframe: At study start; prior to treatment (week 0)
| Intervention | units on a scale (Mean) |
|---|
| Taxane Group: Multivitamin (MV) Arm | 8.5 |
| Taxane Group: MV + Vitamin B12 + Vitamin B6 | 7.3 |
| Heavy Metals Group: Multivitamin (MV) Arm | 5.23 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | 4.58 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | 6.80 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | 2.08 |
Neurotoxicity Assessment at Cycle 4
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 16 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at completion of cycle 4 of their chemotherapy treatment and the mean total score for all patients is reported. (NCT00659269)
Timeframe: 4 weeks
| Intervention | units on a scale (Mean) |
|---|
| Taxane Group: Multivitamin (MV) Arm | 14.5 |
| Multivitamin + Vitamin B12 + Vitamin B6 | 14.5 |
| Heavy Metals Group: Multivitamin (MV) Arm | 8.71 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | 7.05 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | 17.5 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | 9.22 |
Neurotoxicity Assessment at Cycle 2
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to complete at completion of cycle 2 of chemotherapy treatment and the mean total score for all patients is reported. (NCT00659269)
Timeframe: 2 weeks
| Intervention | units on a scale (Mean) |
|---|
| Taxane Group: Multivitamin (MV) Arm | 13.0 |
| Taxane Group: MV + Vitamin B12 + Vitamin B6 | 12.0 |
| Heavy Metals Group: Multivitamin (MV) Arm | 9.7 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | 8.4 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | 14.56 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | 5.6 |
Change in Neurotoxicity Assessment Between Cycle 4 and Baseline
Neurotoxicity is evaluated using The Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) questionnaire. FACT-Tax is a validated, self-reported instrument. The questionnaire consists of 11 questions and possible scores for each question range from 0 (no neurotoxicity symptoms) to 4 (worst possible neurotoxicity symptoms). The total score for any patient can therefore range from 0 to 44. The questionnaire is given to patients to fill out at baseline, cycle 2, and cycle 4 of their chemotherapy treatment. Change in neurotoxicity scores from baseline to the completion of 4 cycles are reported as the mean total score for all patients. (NCT00659269)
Timeframe: 4 weeks
| Intervention | units on a scale (Mean) |
|---|
| Taxane Group: Multivitamin (MV) Arm | 7.0 |
| Taxane Group: MV + Vitamin B12 + Vitamin B6 | 7.2 |
| Heavy Metals Group: Multivitamin (MV) Arm | 3.9 |
| Heavy Metals Group: MV + Vitamin B12 + Vitamin B6 Arm | 4.7 |
| Vinca Alkaloids Group: Multivitamin (MV) Arm | 11.8 |
| Vinca Alkaloids Group: MV + Vitamin B12 + Vitamin B6 Arm | 7 |
Toxicities Associated With Treatment (Grade 1-2)
Toxicity was graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. The most common grade 1-2 non-hematologic and hematologic toxicities were collected for this outcome. (NCT00660699)
Timeframe: 30 days after completion of treatment (treatment lasts approximately 19 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Mucositis | Nausea | Vomiting | Diarrhea | Dehydration | Weight loss | Fatigue | Renal toxicity | Hepatotoxicity | Infection | Neutropenia | Anemia | Thrombocytopenia |
|---|
| Arm 1 | 31 | 48 | 23 | 31 | 17 | 27 | 67 | 13 | 69 | 13 | 46 | 65 | 46 |
Overall Survival (OS)
OS was defined as the time from the initiation of treatment to death from any cause or last follow-up (NCT00660699)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Pancreatic cancer | Biliary/ampullary cancer |
|---|
| Arm 1 | 32.1 | 49.1 |
Overall Survival (OS)
OS was defined as the time from the initiation of treatment to death from any cause or last follow-up (NCT00660699)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Pancreatic cancer | Biliary/ampullary cancer |
|---|
| Arm 1 | 60.7 | 75.0 | 78.6 | 81.2 |
Toxicities Associated With Treatment (Grade 3-4)
Toxicity was graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0. The most common grade 3-4 non-hematologic and hematologic toxicities were collected for this outcome. (NCT00660699)
Timeframe: 30 days after completion of treatment (treatment lasts approximately 19 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Mucositis | Nausea | Vomiting | Diarrhea | Dehydration | Weight loss | Fatigue | Renal toxicity | Hepatotoxicity | Infection | Neutropenia | Anemia | Thrombocytopenia |
|---|
| Arm 1 | 2 | 4 | 4 | 15 | 4 | 0 | 8 | 0 | 4 | 15 | 23 | 4 | 6 |
Incidence of Severe Toxicities
Toxicity was graded according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0 (NCT00660699)
Timeframe: 1 month after completion of treatment (treatment lasts approximately 19 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 20 |
Incidence of Disease Recurrence
(NCT00660699)
Timeframe: Median follow-up was 24 months (range 3.2-97 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm 1 | 83 |
Response Rate
Estimated based on the number of responses by excluding the dropouts who are not evaluable for response using a binomial distribution (NCT00660816)
Timeframe: 36 months after enrollment of last evaluable patient
| Intervention | participants (Number) |
|---|
| Active Comparator | 2 |
| Experimental | 3 |
Progression-free Survival
From the date of randomization to the date of disease progression or the date of death, whichever occurs first and censored at the date of last followed for those survivors without disease progression. (NCT00660816)
Timeframe: 18 months after enrollment of last patient
| Intervention | Months (Median) |
|---|
| Active Comparator | 5.5 |
| Experimental | 4.4 |
Overall Survival
Measured from the date of randomization to the date of death, whichever occurs first and censored at the date of last followed for those survivors (NCT00660816)
Timeframe: 36 months after enrollment of last patient
| Intervention | Months (Median) |
|---|
| Active Comparator | 16.4 |
| Experimental | 14.2 |
Disease Stabilization Rate (e.g., Complete Response, Partial Response, and Stable Disease)
Estimated based on number of evaluable patients with complete response, partial response or stable disease (NCT00660816)
Timeframe: 36 months after enrollment of last patient
| Intervention | participants (Number) |
|---|
| Active Comparator | 15 |
| Experimental | 16 |
Progression-free Survival
Progression-free survival was defined as the time from enrollment in the study to the first documented disease progression using Response Evaluation Criteria In Solid Tumors (RECIST) or death from any cause, whichever occurred first. (NCT00661778)
Timeframe: Baseline to the end of the study (up to 4 years)
| Intervention | Months (Median) |
|---|
| Bevacizumab + Cisplatin + Docetaxel | 8.95 |
Percentage of Participants With an Objective Response
An objective response was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST). Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. (NCT00661778)
Timeframe: Baseline to the end of the study (up to 4 years)
| Intervention | Percentage of participants (Number) |
|---|
| Bevacizumab + Cisplatin + Docetaxel | 67.39 |
1-year Survival
The probability of surviving 1 year was estimated using the Kaplan-Meier method. (NCT00661778)
Timeframe: Baseline to 1 year
| Intervention | Percentage of participants (Number) |
|---|
| Bevacizumab + Cisplatin + Docetaxel | 53.46 |
Overall Survival
Overall survival is defined as the time from the first dose of study medication until death. (NCT00661778)
Timeframe: Baseline to the end of the study (up to 4 years)
| Intervention | Months (Median) |
|---|
| Bevacizumab + Cisplatin + Docetaxel | 12.74 |
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
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Progressive Disease | Stable Disease |
|---|
| Chemo-radio Therapy | 6 | 33 | 5 | 13 |
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)
| Intervention | Months (Median) |
|---|
| Chemo-radio Therapy | 11 |
Time to Disease Progression
Time to disease progression in months (NCT00664105)
Timeframe: on-study date to date of progression
| Intervention | Months (Median) |
|---|
| Chemo-radio Therapy | 5 |
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.
| Intervention | participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Chemo-radio Therapy | 11 | 19 | 35 | 12 | 3 |
Complete Radiological Response (rCR)
"Radiological response is defined according to RECIST 1.0 criteria:~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,~Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of target the appearance of one or more new lesions,~Stable disease (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" (NCT00665392)
Timeframe: At 3 months after the end of 3 cycles of the ETPF combination
| Intervention | participants (Number) |
|---|
| Tumor response rate - Tumor | Tumor response rate - Node | Tumor response rate - Tumor and node |
|---|
| ETPF Administration | 14 | 8 | 4 |
Pathologic Response
"On primary tumor resected : measure of persistence or not of tumoral lesion, histological type, size and quality of the excision piece~A pathological complete response is defined as no viable tumour cells detected on histological examination post surgery." (NCT00665392)
Timeframe: after surgery of the primary tumor
| Intervention | participants (Number) |
|---|
| ETPF Administration | 9 |
The 2-year Estimated Overall Survival (OS) Rate
2-year OS measured survival at 2 years from randomization. (NCT00665392)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| ETPF Administration | 82 |
The 2-year Estimated Progression-free Survival (PFS)
2-year PFS measured survival at 2 years from randomization. (NCT00665392)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| ETPF Administration | 64 |
Biomarkers Analysis - HPV Genotyping
(NCT00665392)
Timeframe: correlative studies investigating HPV status in tumor and blood samples obtained prior to and after induction therapy were done for exploratory purposes as planned in the protocol
| Intervention | participants (Number) |
|---|
| HPV16 - Positive | HPV16 - Negative |
|---|
| ETPF Administration | 17 | 25 |
Clinical and Radiological Complete Clinical Response (crCR) Rate at 3 Months
The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination (NCT00665392)
Timeframe: at 3 months after ETPF combination
| Intervention | participants (Number) |
|---|
| Tumor response Rate - Tumor | Tumor response rate - node | Tumor response rate - Tumor and node |
|---|
| ETPF Administration | 9 | 8 | 4 |
Complete Clinical Response (cCR)
"Clinical complete response (cCR) is defined by:~Disappearance of all clinical evidence of visible tumor,~Disappearance of all palpable residual infiltration,~Disappearance of all evidence of residual visible tumor on CT scan in pharynx and parapharyngeal space,~Complete symmetric remobilization of the tongue and amygdala.~Disappearance of pre-existing trismus.~Negative control biopsy.~The evaluation of tumor response rate was assessed by computed tomography scan of the neck and chest at Baseline, then at 3 months from inclusion using RECIST1.0 criteria and clinical examination" (NCT00665392)
Timeframe: at 3 months
| Intervention | participants (Number) |
|---|
| Tumor response rate - tumor | Tumor response rate - node | Tumor response rate - Tumor and node |
|---|
| ETPF Administration | 17 | 15 | 13 |
Number of Participants With Grade 4 Adverse Events
Grading of adverse events was determine by the principal investigator according to NCI common toxicity criteria (CTC version 3.0). Safety analysis is based on any participant experiencing a grade 4 AE. (NCT00665457)
Timeframe: every 3 weeks X 4, then every 2 weeks X4
| Intervention | Participants (Count of Participants) |
|---|
| Celecoxib | 1 |
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 (NCT00667251)
Timeframe: From randomization to RECIST V 1.0 progression or death assessed up to 39 months.
| Intervention | Months (Median) |
|---|
| ITT n=326, 326 | HER2+n=270, 267 |
|---|
| Lapatinib | 8.97 | 9.13 |
,| Trastuzumab | 11.30 | 13.63 |
Clinical Benefit Response Rate (HER2/Neu+))
Best overall response of CR, PR, or stable disease at end of week 24. (NCT00667251)
Timeframe: 24 weeks
| Intervention | Participants (Number) |
|---|
| Lapatinib | 180 |
| Trastuzumab | 195 |
Clinical Benefit Response Rate (ITT)
Best overall response of CR, PR or stable disease at end of week 24. (NCT00667251)
Timeframe: 24 weeks
| Intervention | Participants (Number) |
|---|
| Lapatinib | 219 |
| Trastuzumab | 230 |
Overall Objective Response Rate (Complete or Partial) HER2/Neu+
Response determined by RECIST V 1.0 (NCT00667251)
Timeframe: Median follow-up of 21.5 months.
| Intervention | Participants (Number) |
|---|
| Lapatinib | 121 |
| Trastuzumab | 130 |
Overall Objective Response Rate (Complete or Partial) ITT
Patients included in this assessment must have had at least one measurable lesion at baseline, and had at least one RECIST re-evaluation after baseline while on protocol therapy, prior to, or on, date of progression. Best overall response was classified to be Complete Response (CR) or Partial Response (PR). (NCT00667251)
Timeframe: 4 years
| Intervention | Participants (Number) |
|---|
| Lapatinib | 139 |
| Trastuzumab | 148 |
Overall Survival
OS median follow-up not achieved; estimated with quartile estimates (NCT00667251)
Timeframe: From randomization to death from any cause, assessed up to 44 months.
| Intervention | Months (Median) |
|---|
| Lapatinib | 20.8 |
| Trastuzumab | 21.8 |
Quality of Life as Measured by the EORTC QLQ-C30 Global Score From Baseline to 12 Weeks
The EORTC QLQ-C30 is a questionnaire developed to assess the quality of life of cancer patients. The global score ranges from 0-100, with higher values representing a better quality of life. At 12 weeks: Group mean difference between arms (NCT00667251)
Timeframe: 12 weeks
| Intervention | Score on global scale (Mean) |
|---|
| Lapatinib | 61.67 |
| Trastuzumab | 64.41 |
Percentage of Patients Who Can Safely Tolerate and Complete Adjuvant Hormonal Therapy, Radiation Therapy and Docetaxel After a Radical Prostatectomy
Defined as percentage of patients that complete full dose of Radiation Therapy (RT) (NCT00669162)
Timeframe: 8 Months
| Intervention | percentage of participants (Number) |
|---|
| RT, Docetaxel, Hormonal Therapy | 26 |
Overall Response Rate (ORR)
ORR = Complete Response (CR) + Partial Response (CR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete Response: Disappearance of all target lesions; 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. (NCT00673738)
Timeframe: Up to 36 months
| Intervention | percentage of participants (Number) |
|---|
| Partial Response | Complete Response |
|---|
| Cetuximab Plus Radiotherapy | 59.3 | 0 |
To Measure the Number of Cycles
Cycle delivery is a surrogate for drug delivery. Both cycle delivery and drug delivery will be measured in this study. However, cycle delivery (up to 4 cycles) is the common way drug delivery is measured in the literature, and therefore cycle delivery has been chosen as the primary endpoint for this study.Two doses of both docetaxel plus vinorelbine, delivered over 4 weeks, constitutes one cycle. If either drug is discontinued, the subject will remain on study, however that patient will not get credit for completing subsequent cycles of therapy. If the dose of either drug is reduced, the subject will remain on study and get credit for subsequent cycles. (NCT00675597)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Completed 4 cycles | Unable to complete 4 cycles |
|---|
| Docetaxel (Taxotere®) Plus Vinorelbine | 20 | 3 |
Clinical Benefit (CB) Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
CB was defined as an objective response (complete response [CR], partial response [PR]) or stable disease (SD) for 6 months after randomization. For target lesions (TL), CR=the disappearance of all TL; PR=at least a 30% decrease in the sum of the longest diameter (LD) of TL, taking as reference the baseline sum LD; SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started; PD=at least a 20% increase in the sum of the LD of TL, taking as reference the smallest sum of the LD recorded since the treatment started or the appearance of 1 or more new lesions. For non-TL, CR=the disappearance of all non-TL; PR=the persistence of 1 or more non-TL; SD=the persistence of 1 or more non-target lesion(s) and/or the maintenance of tumor marker level above the normal limits; PD=the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TL. (NCT00679341)
Timeframe: Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
| Intervention | Percentage of patients (Number) |
|---|
| Trastuzumab Emtansine | 74.6 |
| Trastuzumab + Docetaxel | 81.2 |
Duration of Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
Duration of objective response was defined as the time from initial response to investigator-assessed radiographic or clinical disease progression or death on study from any cause. For target lesions, 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 of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, disease progression was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions should be selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, should be identified as target lesions. (NCT00679341)
Timeframe: Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
| Intervention | Months (Median) |
|---|
| Trastuzumab Emtansine | NA |
| Trastuzumab + Docetaxel | 9.5 |
Objective Response Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST)
A patient had an objective response if they had a complete response or a partial response on 2 consecutive occasions ≥ 4 weeks apart. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions. (NCT00679341)
Timeframe: Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
| Intervention | Percentage of patients (Number) |
|---|
| Trastuzumab Emtansine | 64.2 |
| Trastuzumab + Docetaxel | 58.0 |
Overall Survival
Overall survival was defined as the time from randomization to the date of death from any cause. Patients who were alive at the time of analysis were censored at the date on which they were last known to be alive. Patients with no post-baseline were censored at the date of randomization plus 1 day. (NCT00679341)
Timeframe: Baseline through the data cut-off date of 31 Aug 2011 (up to 2 years, 11 months)
| Intervention | Months (Median) |
|---|
| Trastuzumab Emtansine | NA |
| Trastuzumab + Docetaxel | NA |
Progression-free Survival (PFS) by the Investigator Using Modified Response Evaluation Criteria In Solid Tumors (RECIST)
PFS was defined as the time from randomization (R) to first documented investigator-assessed radiographic or clinical disease progression (PD) or death due to any cause, whichever occurred first. For target lesions (TL), PD was defined as at least a 20% increase in the sum of the longest diameter (SLD) of TLs, taking as reference the SLD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. Data for patients without PD or death were censored at the last date of tumor assessment prior to crossover (or, if no tumor assessment was performed after Baseline, at the R date +1 day). Data for patients who were lost to follow-up were censored at the last date of tumor assessment prior to crossover at which the patient was known to be progression free. Data for patients with no post-baseline tumor assessment were censored at the R date +1 day. (NCT00679341)
Timeframe: Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
| Intervention | Months (Median) |
|---|
| Trastuzumab Emtansine | 14.2 |
| Trastuzumab + Docetaxel | 9.2 |
Time to Symptom Progression
Time to symptom progression was defined as the time from randomization to the first documentation of a ≥ 5-point decrease from baseline in the Trial Outcome Index-Physical/Functional/Breast (TOI-PFB) subscale score of the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire. The FACT-B questionnaire is a valid and reliable measure of symptoms associated with breast cancer. The TOI-PFB is a 24-item subscale generated using 3 subsections (Physical Well-Being [7 items], Functional Well-Being [7 items], and Additional Concerns [10 items]) from the FACT-B questionnaire. Patients responded to each item on a scale of 0-4 (Not at all-Very much). The total score ranged from 0 to 96. A higher score indicates fewer symptoms. A positive change score indicates improvement. (NCT00679341)
Timeframe: Baseline through the data cut-off date of 15 Nov 2010 (up to 2 years, 2 months)
| Intervention | Months (Median) |
|---|
| Trastuzumab Emtansine | 7.5 |
| Trastuzumab + Docetaxel | 3.5 |
Plasma Concentration of Free Emtansine
Plasma samples were collected from all 67 patients in the trastuzumab emtansine group 30 minutes post-infusion of trastuzumab emtansine at Cycles 1 and 5. The plasma samples were assayed for free emtansine in a mass-spectrometric assay. (NCT00679341)
Timeframe: Baseline through Cycle 5 (up to 4 months)
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 (n=62) | Cycle 5 (n=39) |
|---|
| Trastuzumab Emtansine 3.6 mg/kg | 5.11 | 4.71 |
Serum Concentrations (Area Under the Concentration-time Curve [AUC]) of Trastuzumab Emtansine and Total Trastuzumab
Serum samples were collected from all 67 patients enrolled in the trastuzumab emtansine arm using sparse pharmacokinetic sampling. Blood samples were collected prior to dosing and 30 minutes post-infusion of trastuzumab emtansine at Cycles 1 and 5. Serum samples were assayed for trastuzumab emtansine and total trastuzumab (sum of unconjugated trastuzumab and emtansine conjugated to trastuzumab) in indirect sandwich ELISAs. The area under the concentration-time curve (AUC) was estimated based on non-compartmental analysis using WinNonlin (Version 5.2.1) software. (NCT00679341)
Timeframe: Baseline through Cycle 5 (up to 4 months)
| Intervention | day•μg/mL (Mean) |
|---|
| Trastuzumab emtansine Cycle 1 (n=62) | Trastuzumab emtansine Cycle 5 (n=39) | Total trastuzumab Cycle 1 (n=60) | Total trastuzumab Cycle 5 (n=38) |
|---|
| Trastuzumab Emtansine 3.6 mg/kg | 495 | 473 | 700 | 788 |
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)
| Intervention | months (Median) |
|---|
| Randomized to Vandetanib Maintenance | 4.5 |
| Randomized to Placebo Maintenance | 4.2 |
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))
| Intervention | Months (Median) |
|---|
| All Randomized Patients | 4.5 |
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))
| Intervention | percentage of participants (Number) |
|---|
| Randomized to Vandetanib Maintenance | 18.8 |
| Randomized to Placebo Maintenance | 18.3 |
Number of Participants Who Had a Tumor Response, According to Standard RECIST (Response Evaluation Criteria in Solid Tumors) Criteria
Those who achieved either complete (disappearance of all target lesions) or partial (at least 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD) response. (NCT00687440)
Timeframe: Week 09, Week 18, at the end of each patient's treatment, and at 3, 6, 9, and 12 months after end of treatment.
| Intervention | Participants (Number) |
|---|
| Participants who had a complete tumor response | Participants who had a partial tumor response | Participants who did not have a tumor response |
|---|
| Caelyx, Docetaxel, Trastuzumab | 2 | 13 | 11 |
Number of Participants With Second Primary Malignancies (Toxicity)
Toxicity (second primary malignancies)- defined as histopathologically proven cancer, excluding nonmelanomatous skin cancer, in situ carcinoma of the cervix, and in situ carcinoma of the breast. (NCT00688740)
Timeframe: up to 10 year follow-up
| Intervention | Participants (Number) |
|---|
| TAC (Docetaxel) | 67 |
| FAC (5-fluorouracil) | 66 |
Number of Participants With Disease-Free Survival Events
Disease-Free Survival (DFS)- are defined as local, regional or metastatic relapse or the date of second primary cancer or death from any cause whichever occurs first. (NCT00688740)
Timeframe: up to 10 year follow-up
| Intervention | Participants (Number) |
|---|
| TAC (Docetaxel) | 287 |
| FAC (5-fluorouracil) | 333 |
Number of Participants With Overall Survival Events
Overall Survival - time from the date of randomization up to the date of death of any cause. (NCT00688740)
Timeframe: up to 10 year follow-up
| Intervention | Participants (Number) |
|---|
| TAC (Docetaxel) | 188 |
| FAC (5-fluorouracil) | 241 |
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Objective Response Rate)
Objective response rate (ORR) was defined as the percentage of randomized participants achieving a best confirmed overall response of CR or PR using Response Evaluation Criteria in Solid Tumors (RECIST v1.0), based on the achievement of both measurement and confirmation criteria; by Investigator assessment. CR was defined as the disappearance of all target and non-target lesions. PR was 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 and no progression in non-target lesions. (NCT00703326)
Timeframe: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
| Intervention | percentage of participants (Number) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | 44.7 |
| Placebo + Docetaxel | 37.9 |
Overall Survival (OS)
OS was defined as the duration from randomization to death from any cause. Participants who were alive at data cut-off for the OS analysis or lost to follow-up were censored on the last date the participant was known to be alive. (NCT00703326)
Timeframe: Randomization to death or until data cutoff of 29-May-2015 (up to 82 months)
| Intervention | months (Median) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | 30.3 |
| Placebo + Docetaxel | 28.7 |
Immunogenicity: Percentage of Participants With Treatment Emergent Anti-Ramucirumab Antibodies Until Primary Data Cutoff of 31-Mar-2013
Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals. (NCT00703326)
Timeframe: Baseline, prior to cycle 3 infusion, prior to cycle 5 infusion, onset of infusion reaction, resolution of reaction and 30 days following the event up to 56 months
| Intervention | percentage of participants (Number) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | 0.8 |
| Placebo + Docetaxel | 0.8 |
Immunogenicity: Percentage of Participants Available After 31-Mar-2013 With Treatment Emergent Anti-Ramucirumab Antibodies Until Data Cutoff From 01-Apr-2013 to 08-Sep-2016
Percentage of participants with treatment-emergent positive for anti-ramucirumab (IMC-1121B) antibodies during the study. Participants were considered positive for anti-ramucirumab (IMC-1121B) antibodies if they exhibited a post-treatment antibody level that exceeded the positive upper cut point determined from the anti-ramucirumab (IMC-1121B) level seen in healthy untreated individuals. (NCT00703326)
Timeframe: Follow-up from 01-Apr-2013 to 08-Sep-2016 (Up to 56 -97 months)
| Intervention | percentage of participants (Number) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | 0 |
| Placebo + Docetaxel | 0 |
Duration of Response
Duration of complete response (CR) or partial response (PR) measured from time criteria were first met for CR or PR until first date of progressive disease (PD) or death from any cause defined using Response Evaluation Criteria in Solid Tumor (RECIST 1.0); by Investigator assessment. CR defined as disappearance of all target and non-target lesions. PR defined as ≥30% decrease in sum of longest diameter (LD) of target lesions and no progression in non-target lesions. PD defined as ≥20% increase in LD sum of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of ≥1 new lesion(s). Participants who did not relapse or die censored at day of last radiographic tumor assessment. If death or PD was after ≥2 missing radiographic visits, censoring was at date of last radiographic visit prior to missed visits. Symptomatic/clinical disease progression without documented radiologic progression did not constitute progression. (NCT00703326)
Timeframe: Date of first CR or PR to PD or death or until data cutoff date of 31-Mar-2013 (up to 56 months)
| Intervention | months (Median) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | 8.4 |
| Placebo + Docetaxel | 8.1 |
Number of Participants With Adverse Events
Clinically significant events were defined as serious adverse events (SAE) and other treatment-emergent non-serious adverse events (NSAE). A summary of SAEs and other NSAEs is located in the Reported Adverse Event module. (NCT00703326)
Timeframe: First dose to study completion (up to 12.3 years)
| Intervention | participants (Number) |
|---|
| Participants with SAEs | Participants with NSAEs |
|---|
| Placebo + Docetaxel | 117 | 373 |
,| Ramucirumab (IMC-1121B) + Docetaxel | 285 | 737 |
Total Functional Assessment of Cancer Therapy-Breast (FACT-B): Change From Baseline to End of Therapy
FACT-B measures the following domains of health-related quality of life (HR-QoL): physical well-being (PWB), social/family well-being (SFWB), emotional well-being (EWB), functional well-being (FWB), and additional concerns of breast cancer subscale (BCS) each with 6 or more items developed to measure problems specific to breast cancer symptoms plus additional items related to global QoL. Participants respond to each of the 36 questions on a 5-point scale from 0 (not at all) to 4 (very much) with a total scores range of 0-144. Higher scores indicate fewer symptoms and better HR-QoL. (NCT00703326)
Timeframe: Baseline, End of Therapy or until data cutoff of 31-Mar-2013 (up to 56 months)
| Intervention | units on a scale (Mean) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | -6.8 |
| Placebo + Docetaxel | -7.0 |
Time to Progression (TTP)
TTP was defined as the time from the date of randomization to the first documented date of disease progression using Response Evaluation Criteria in Solid Tumors (RECIST v1.0) criteria; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who did not progress were censored at the last radiographic tumor assessment. If no post-baseline assessment was available censoring occurred at the date of randomization. If PD occurred after 2 or more missing radiographic visits, censoring occurred at the date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression. (NCT00703326)
Timeframe: Randomization to disease progression or until data cutoff of 31-Mar-2013 (up to 56 months)
| Intervention | months (Median) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | 9.7 |
| Placebo + Docetaxel | 8.2 |
Progression-Free Survival (PFS)
PFS was defined as time from randomization until the first evidence of progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0) or death from any cause; by Investigator assessment. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions taking as reference the smallest sum longest diameter since baseline, progression in non-target lesions or the appearance of 1 or more new lesion(s). Participants who neither progressed nor died were censored the day of their last radiographic tumor assessment if available or date of randomization if no post initiation radiographic assessment was available. If death or PD occurred after ≥2 missing radiographic visits, censoring occurred at date of the last radiographic visit prior to the missed visits. The symptomatic/clinical disease progression (deterioration) without documented radiologic progression did not constitute progression. (NCT00703326)
Timeframe: Randomization to disease progression or death or until data cutoff of 31 Mar 2013 (up to 56 months)
| Intervention | months (Median) |
|---|
| Ramucirumab (IMC-1121B) + Docetaxel | 9.5 |
| Placebo + Docetaxel | 8.2 |
Maximum Tolerated Dose (MTD)
"The MTD was defined as the dose below which one-third of at least 6 patients (2/6) experienced a dose limiting toxicity (DLT).~DLTs had to occur during cycle 1 of treatment and had to be considered related to PG-11047:~Any nonhematologic toxicity > Grade 3 lasting > 3 days~Grade 4 thrombocytopenia~Grade 4 Anemia on the next scheduled dosing day~Grade 4 Neutropenia (lasting > than 5 days~Any febrile neutropenia (Grade 3 or 4))~Inability to receive all scheduled doses of PG-11047 during the first dosing cycle due to drug related toxicity" (NCT00705874)
Timeframe: End of Study
| Intervention | mg (Number) |
|---|
| PG11047/Gemcitabine | NA |
| PG11047/Docetaxel | NA |
| PG11047/Bevacizumab | 590 |
| PG11047/Erlotinib | 590 |
| PG11047/Cisplatin | 590 |
| PG11047/5-Flurouracil | 590 |
| PG11047/Sunitinib | NA |
Toxicity Profile
"Toxicity data will be collected on day 1 of every 14 day cycle during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events (AE) version 3.0 (CTCAE v3.0). For patients that experience multiple grades of the same AE that is determined to be at least possibly related to at least one study drug, only highest grade will be collected. In general 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" (NCT00711243)
Timeframe: Day 1 of each cycle of therapy with 1 cycle =14 days until disease progression for up to a maximum of 34 cycles and 30 days after last treatment
| Intervention | participants (Number) |
|---|
| Neutropenia | Leukopenia | Lymphopenia | Anemia | Thrombocytopenia | Fatigue | Vomiting | Dehydration | Infection | Nausea | Pain | Allergy | Transaminitis | Rash | Weight loss | Anorexia | Fever | Hypertension | Hyperglycemia | Diarrhea | Constipation | Mucositis | Neuro-sens | Neuro-motor | Nail changes | Alopecia | Skin | Hemorrhage | Altered taste | Edema | Abdominal distension | Shortness of breath |
|---|
| Phase II | 23 | 31 | 15 | 30 | 13 | 36 | 22 | 5 | 4 | 31 | 5 | 4 | 7 | 3 | 6 | 13 | 4 | 2 | 3 | 22 | 10 | 14 | 30 | 2 | 2 | 6 | 6 | 5 | 6 | 2 | 2 | 6 |
Response Rate in Patients With Adenocarcinoma of the Stomach or Gastroesophageal Junction (Phase II)
"Overall Response Rate (ORR) is defined as Complete Response (CR) plus Partial Response (PR) and will be measured per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT scan.~Complete Response (CR) - Disappearance of all target lesions. Partial Response (PR), >=30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum.~Stable Disease, neither sufficient shrinkage to qualify for Partial disease nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD while on study.~Progressive Disease - <=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." (NCT00711243)
Timeframe: After 4 cycles of therapy (1 cycle = 14 days)
| Intervention | percentage of patients (Number) |
|---|
| Phase II | 73.2 |
Dose-limiting Toxicity of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil
"Dose limiting toxicities (DLT) will be graded according to National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0) except for neurosensory. The occurrence of any of the following during the 1st cycle, seen in more than one patient, will constitute a DLT.~Grade 3 non-hematologic toxicity(except alopecia) Grade 4 thrombocytopenia, not recovered to platelet count of >75,000/ul by day 15.~Grade 4 neutropenia, not recovered to count of >1,500/ul by day 15. Grade 4 neutropenia with fever or infection. Grade 2 neurologic-sensory toxicity not recovered to grade 1 or better by day 15" (NCT00711243)
Timeframe: After 1 cycle of therapy (1 cycle = 14 days)
| Intervention | participants (Number) |
|---|
| Fatigue | Diarrhea |
|---|
| Cohort 1a | 0 | 0 |
,| Cohort 2a | 0 | 0 |
,| Cohort 3a | 0 | 0 |
,| Cohort 4a | 0 | 0 |
,| Cohort 5a | 2 | 2 |
Maximum Tolerated Dose (MTD) of Docetaxel When Given in Combination With Oxaliplatin and Fluorouracil (Phase I)
"The MTD will be determined using a 3+3 dose escalating design. There will be 5 dose cohorts:~Cohort 1a 25mg/m2 Cohort 2a 30mg/m2 Cohort 3a 40 mg/m2 Cohort 4a 50 mg/m2 Cohort 5a 60 mg/m2~3 patients will be enrolled at dose of 25mg/m2 docetaxel. If no dose limiting toxicities (DLTs) are seen then dose will be escalated to next cohort and 3 patients will be treated at that dose level. If a DLT is seen at any dose, then 3 more patients will be enrolled at that dose level. If 1 patient out of 6, experience a DLT then MTD will be determined to be at this dose level. If 2 or more DLTs are seen in first 3 patients at that dose, then MTD will be one dose lower to the level where the DLTs were experienced. Dose of docetaxel will be escalated by use of cohorts until the MTD for phase II is determined.~DLTs were defined using the National Cancer Institute Common Toxicity Criteria Version 3.0" (NCT00711243)
Timeframe: After completion of 1 cycle of therapy (1 cycle = 14 days)
| Intervention | mg/m2 (Number) |
|---|
| Phase I | 50 |
Overall Progression-Free Survival (PFS).
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 measureable increase in a non-target lesion, or the appearance of new lesions. (NCT00713219)
Timeframe: conclusion of the study
| Intervention | Days (Mean) |
|---|
| Docetaxel + Cetuximab + Concurrent Re-Irradiation | 370 |
Quality of Life - Functional Assessment of Cancer Therapy - General (FACT-G)
"Four subscales: physical well-being (PWB; 7-items, score range 0-28), social/family well-being (SWB; 7-items, score range 0-28), emotional well-being (EWB; 6-items, score range 0-24), and functional well-being (FWB; 7-items, score range 0-28). Items are rated on a five-point scale: 0-not at all, 1- a little bit, 2-somewhat, 3- quite a bit and 4-very much. Overall quality of life is the sum of the core items of the FACT-G possible range of 0-108 points. The higher the score the better the quality life. This interval includes 0, we will conclude that there is not conclusive statistical evidence that there is an improvement or worsening. If the interval does not include 0 we can determine whether there was a significant improvement (or worsening) depending on which side of the 0 the interval is on. The total outcome index score (possible range 0-108 points) is the sum of the physical and functional well being and additional concerns categories from the FACT-G." (NCT00721513)
Timeframe: Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years
| Intervention | Score on a scale (Mean) |
|---|
| Baseline - Physical Well-Being | Baseline - Social/Family Well-Being | Baseline - Emotional Well-Being | Baseline Functional Well-Being | Baseline Total Fact-G Score | Baseline Additional Concerns | Total Outcome Index Score - Baseline | Pre-RT Physical Well-Being | Pre-RT Social/Family Well-Being | Pre-RT Emotional Well-Being | Pre-RT Functional Well-Being | Pre-RT Total Fact-G Score | Pre-RT Additional Concerns | Total Outcome Index Score - Pre-RT | Post-RT Social/Family Well-Being | Post-RT Physical Well-Being | Post-RT Emotional Well-Bein | Post-RT Functional Well-Being | Post-RT FACT-G Total Score | Post-RT Additional Concerns | Total Outcome Index Score - Post- RT |
|---|
| TPFChemotherapy + Concomitant Cetuximab & RT | 17.21 | 23.66 | 17.00 | 17.48 | 75.35 | 23.25 | 57.94 | 15.56 | 23.90 | 18.80 | 15.63 | 72.00 | 25.44 | 55.78 | 23.80 | 16.42 | 18.93 | 15.92 | 75.07 | 21.28 | 50.00 |
MD Anderson Dysphagia Inventory
The MD Anderson Dysphasia Inventory (MDADI) is a survey specifically designed to assess dysphasia. It contains 20 questions directly addressing the swallowing function and several other general questions. The questionnaire asks for participants views about their swallowing ability at baseline, pre-radiation therapy and post-radiation therapy. All questions except for E7 and F2: Strongly Agree = 1 point, Agree = 2 points, No Opinion = 3 points, Disagree = 4 points, Strongly Disagree. E7 and F2: Strongly agree = 5 points, Agree = 4 points, no opinion = 3 points, disagree = 2 points, strongly disagree = 1 point. Scores range from 20 (extremely low-functioning) to 100 (high-functioning). (NCT00721513)
Timeframe: Baseline, pre-radiation therapy and post-radiation therapy, up to 2 years
| Intervention | Score on a scale (Mean) |
|---|
| Baseline Global Score | Baseline Emotion Score | Baseline Function Score | Baseline Physical Score | Pre-RT Global Score | Pre-RT Emotion Score | Pre-RT Function Score | Pre-RT Physical Score | Post-RT Global Score | Post-RT Emotion Score | Post-RT Function Score | Post-RT Physical Score |
|---|
| TPFChemotherapy + Concomitant Cetuximab & RT | 56.00 | 71.48 | 75.56 | 68.00 | 88.00 | 83.07 | 76.80 | 86.00 | 62.50 | 67.08 | 58.29 | 67.81 |
Progression-free Survival
(NCT00721513)
Timeframe: up to 2 years
| Intervention | months (Median) |
|---|
| TPFChemotherapy + Concomitant Cetuximab & RT | 54.2 |
Overall Survival
(NCT00721513)
Timeframe: up to 2 years
| Intervention | months (Median) |
|---|
| TPFChemotherapy + Concomitant Cetuximab & RT | 53.6 |
Number of Participants With Local-Regional Control
(NCT00721513)
Timeframe: up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| TPFChemotherapy + Concomitant Cetuximab & RT | 20 |
The Rate of Progression Free Survival (PFS) at 24 Months
Percentage of participants surviving 24 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. Progression will be defined as having experienced any of the following: a serum prostate specific antigen (PSA) value of 0.2 ng/mL or more above the post-radiotherapy PSA nadir and confirmed 4 weeks later by a second PSA measurement that was higher than the first by any amount, a continued rise in the PSA level following study treatment if no nadir is experienced, defined as 2 rising values greater than the baseline PSA and separated by at least 4 weeks, or evidence of clinical progression or initiation of systemic therapy for progressive disease. (NCT00734851)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| Multimodality | 51 |
Proportion of Biochemical Progression (bPFS Proportion) at 2 and 3 Years.
Percentage of participants surviving 24 and 36 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. Progression will be defined as having experienced any of the following: a serum prostate specific antigen (PSA) value of 0.2 ng/mL or more above the post-radiotherapy PSA nadir and confirmed 4 weeks later by a second PSA measurement that was higher than the first by any amount or a continued rise in the PSA level following study treatment if no nadir is experienced, defined as 2 rising values greater than the baseline PSA and separated by at least 4 weeks. Please note: bPFS is identical to PFS but includes only PSA-based endpoints or death. (NCT00734851)
Timeframe: 24 months and 36 months
| Intervention | percentage of patients (Number) |
|---|
| 24 Months | 36 Months |
|---|
| Multimodality | 51 | 48 |
Rate of Local Recurrence at 2 and 3 Years
Local recurrence is defined as men with locally recurrent disease confirmed pathologically within the radiation field, and is estimated at 2 and 3 years. (NCT00734851)
Timeframe: 24 months and 36 months
| Intervention | percentage of participants (Number) |
|---|
| 24 Months | 36 Months |
|---|
| Multimodality | 0 | 0 |
Change in Quality of Life (QoL) After 3 Month
A validated scale of prostate-cancer specific quality of life will be measured using the Expanded Prostate Cancer Index Composite (EPIC) short form survey. This survey is standardized into subscale, 4 of which were examined on this study. These subscales are the urinary irritative domain, urinary incontinence domain, bowel domain, and sexual function domain, each standardized on a scale of 0-100, where higher score indicate a higher level of QoL. The survey was performed at baseline and 3 months after completing radiotherapy. Negative values indicate a decrease in QoL, while positive numbers represent an increase. (NCT00734851)
Timeframe: baseline and 3 months
| Intervention | units on a scale (Median) |
|---|
| Urinary Irritative (N=29) | Urinary Incontinence (N=31) | Bowel (N=32) | Sexual (N=30) |
|---|
| Multimodality | 0 | -6 | 0 | 0 |
Change in Quality of Life (QoL) After 1 Year
A validated scale of prostate-cancer specific quality of life will be measured using the Expanded Prostate Cancer Index Composite (EPIC) short form survey. This survey is standardized into subscale, 4 of which were examined on this study. These subscales are the urinary irritative domain, urinary incontinence domain, bowel domain, and sexual function domain, each standardized on a scale of 0-100, where higher score indicate a higher level of QoL. The survey was performed at baseline, at 3 months after completing radiotherapy, at 12 months, and at 2 and 3 years of follow-up for a total of 5 possible surveys per patient. Due to a low number of completed surveys at the fourth and fifth time point, the difference between the 12 month time point and baseline is summarized. Negative values indicate a decrease in QoL, while positive numbers represent an increase. (NCT00734851)
Timeframe: baseline and 1 year
| Intervention | units on a scale (Median) |
|---|
| Urinary Irritative (N=20) | Urinary Incontinence (N=21) | Bowel (N=19) | Sexual (N=21) |
|---|
| Multimodality | 0 | 0 | 0 | 0 |
Overall Response Will be Characterized by the Patient's FDG-PET Scan
A good early FDG Response is a reduction in FDG uptake on the week 3 PET scan of > or = to 35% from baseline. An FDG PET non-responder will be defined as having a decrease of < 35% on the week 3 PET scan compared with baseline. (NCT00737438)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Metabolic Responder | Non-Metabolic Responder |
|---|
| All Patients | 11 | 9 |
Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology
Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening ). Grade 3 and 4 criteria are defined as follows: Absolute neutrophil count, Grade 3, neutrophils <1.0-0.5*10^9/L; Grade 4, <0.5*10^9/L. Hemoglobin, Grade 3, <4.9-4.0 mmol/L; Grade 4, <4.0 mmol/L. Platelets, Grade 3, <50.0-25.0*10^9/L; Grade 4, <25.0*10^9/L. Leukocytes, Grade 3, <2.0-1.0*10^9/L; Grade 4, <1.0*10^9/L. (NCT00744497)
Timeframe: At baseline, within 3 days prior to each infusion of docetaxel (each cycle) and at end of treatment. If docetaxel is discontinued, every other cycle.
| Intervention | Participants (Number) |
|---|
| Absolute neutrophil count (All grades) | Absolute neutrophil count (Grades 3 and 4) | Hemoglobin (All grades) | Hemoglobin (Grades 3 and 4) | Platelets (All grades) | Platelets (Grades 3 and 4) | Leukocytes (All grades) | Leukocytes (Grades 3 and 4) |
|---|
| Dasatinib | 161 | 46 | 720 | 59 | 100 | 3 | 149 | 30 |
,| Placebo | 84 | 41 | 712 | 44 | 108 | 6 | 128 | 32 |
Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal. Abnormalities were graded according to the Common Toxicity Criteria (CTC), version 3.0, of the National Cancer Institute. CTC are graded from 1 (least severe) to 4 (life threatening). ALP, ALT, and AST, Grade 3, >5.0-20.0*ULN; Grade 4, >20.0*ULN. Total bilirubin, Grade 3, >3.0-10.0*ULN; Grade 4, >10.0*ULN. Creatinine, Grade 3, >3.0-6.0*ULN; Grade 4, >6.0*ULN. Hypercalcemia(serum calcium, mmol/L), Grade 3, >3.1-3.4; Grade 4, >3.4. Hypocalcemia (serum calcium, mmol/L), Grade 3, <1.75-1.5; Grade 4, <1.5. Hyperkalemia(serum calcium, mmol/L), Grade 3, >6.0-7.0; Grade 4, >7.0. Hypokalemia(serum calcium, mmol/L), Grade 3, <3.0-2.5; Grade 4, <2.5. Hypernatremia (serum calcium, mmol/L), Grade 3, >155-160; Grade 4, >160. Hyponatremia (serum sodium, mmol/L), Grade 3, <130-120; Grade 4, <120. Phosphorus (serum sodium, mmol/L), Grade 3, <0.6-0.3; Grade 4, <0.3. (NCT00744497)
Timeframe: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.
| Intervention | Participants (Number) |
|---|
| ALP (All grades) | ALP (Grades 3 and 4) | ALT (All grades) | ALT (Grades 3 and 4) | AST (All grades) | AST (Grades 3 and 4) | Total bilirubin (All grades) | Total bilirubin (Grades 3 and 4) | Creatinine (All grades) | Creatinine (Grades 3 and 4) | Hypercalcemia (All grades) | Hypercalcemia (Grades 3 and 4) | Hypocalcemia (All grades) | Hypocalcemia (Grades 3 and 4) | Hyperkalemia (All grades) | Hyperkalemia (Grades 3 and 4) | Hypokalemia (All grades) | Hypokalemia (Grades 3 and 4) | Hypernatremia (All grades) | Hypernatremia (Grades 3 and 4) | Hyponatremia (All grades) | Hyponatremia (Grades 3 and 4) | Phosporus (All grades) | Phosphorus (Grades 3 and 4) |
|---|
| Dasatinib | 375 | 68 | 256 | 6 | 266 | 5 | 41 | 3 | 184 | 5 | 34 | 1 | 377 | 25 | 152 | 14 | 152 | 16 | 101 | 0 | 241 | 43 | 257 | 93 |
,| Placebo | 447 | 91 | 186 | 5 | 212 | 4 | 49 | 1 | 153 | 3 | 56 | 1 | 308 | 23 | 164 | 11 | 107 | 6 | 93 | 0 | 230 | 36 | 189 | 43 |
Percentage of Participants With a Reduction in Pain Intensity From Baseline
The percentage of participants with a reduction in pain intensity from baseline was defined as the number of participants who achieved a 30% or more decrease in pain intensity from baseline for at least 2 consecutive pain assessments (at least 14 days apart) within 14 days of end of dosing divided by the number of randomized participants who had a baseline pain intensity of at least 2. Pain intensity was assessed based on question 3 of the brief pain inventory questionnaire. (NCT00744497)
Timeframe: At baseline, prior to each docetaxel infusion (every 3 weeks), at end of treatment, and at follow-up (within 14 days of end of dosing)
| Intervention | Percentage of participants (Number) |
|---|
| Placebo | 71.52 |
| Dasatinib | 66.59 |
Overall Survival: Time From Randomization to Date of Death
Overall survival is defined as time in months from the randomization date to the date of death due to any cause (in the randomized population). If the patient did not die, survival was censored on the last date he or she was known to be alive. (NCT00744497)
Timeframe: From randomization to death or date of last contact (maximum reached: 45 months)
| Intervention | Months (Median) |
|---|
| Placebo | 21.2 |
| Dasatinib | 21.5 |
Number of Participants With Abnormal Results in Urinalysis
Abnormal=positive, defined as the presence of >=30 mg/dL of protein; a small, moderate, or large amount of blood; or >0 g/dL glucose in urine. BL=baseline; neg=negative (NCT00744497)
Timeframe: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle.
| Intervention | Participants (Number) |
|---|
| Protein, urine: postive | Blood, urine: positive | Glucose, urine: positive |
|---|
| Dasatinib | 336 | 307 | 154 |
,| Placebo | 246 | 289 | 179 |
Number of Participants by Maximal On-study Fridericia-corrected QTc Interval
QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included. (NCT00744497)
Timeframe: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing
| Intervention | Participants (Number) |
|---|
| <450 msecs (n=600, 548) | 450-500 msecs (n=600, 548) | >500 msecs (n=600, 548) |
|---|
| Dasatinib | 497 | 48 | 3 |
,| Placebo | 550 | 43 | 7 |
Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline
The percentage of participants who had an on-study uNTx value confirmed (at least 3 weeks later) within normal limits (or ≥3 and <60 nmol/mmol creatinine, if normal limits were missing) or an on-study uNTx level reduction from baseline of ≥35%, even when on-study uNTx value remained abnormal. (NCT00744497)
Timeframe: At baseline, prior to each docetaxel infusion (every 3 weeks) to end of treatment, at end of treatment, and at follow-up (within 14 days of end of dosing)
| Intervention | Percentage of participants (Number) |
|---|
| Placebo | 60.60 |
| Dasatinib | 66.04 |
Progression-free Survival (PFS)
PFS is defined as the time from the randomization date until the date of earliest evidence of disease progression or death, for participants who progressed or died before subsequent cancer therapy. Those who progressed or died while on subsequent cancer therapy and those who did not die or progress were censored at their last radiologic bone scan/imaging, skeletal related-event, or tumor assessment or at measurement of prostate specific antigen levels, whichever occurred last prior to start of subsequent cancer therapy ,if any. Participants with no assessments were censored on the day of randomization. (NCT00744497)
Timeframe: From day of randomization to disease progression or death (or to last clinical assessment, if subsequent cancer therapy started or no progression or death) (maximum reached: approximately 43 months)
| Intervention | Months (Median) |
|---|
| Placebo | 11.1 |
| Dasatinib | 11.8 |
Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)
Objective tumor response rate=the percentage of randomized participants with a best tumor response of partial (PR) or complete response (CR), within 42 days of end of dosing, divided by total number of patients who were evaluable (with at least 1 target lesion at baseline). By RECIST: CR=disappearance of clinical and radiologic evidence of target and nontarget lesions confirmed by another evaluation at least 6 weeks later. PR=a >30% or greater decrease in the sum of longest diameter (LD) of target lesions in reference to the baseline sum LD confirmed by another evaluation at least 6 weeks later. Stable disease=neither sufficient increase to qualify for PD nor shrinkage to qualify for PR, and at least 8 weeks since start of study therapy. Progressive disease=a 20% or greater increase in sum of LD of all target lesions, taking as reference the smallest sum of LD at or following baseline, or unequivocal progression on existing nontarget lesions, or new lesions are present. (NCT00744497)
Timeframe: At baseline and every 12 weeks thereafter to end of treatment, at end of treatment, and at follow-up (within 42 days of end of dosing)
| Intervention | Percentage of participants (Number) |
|---|
| Placebo | 31.85 |
| Dasatinib | 30.45 |
Time to Prostate Specific Antigen (PSA) Progression
PSA progression is defined as the time from randomization to the date of the first PSA level measurement that led to confirmed PSA progression, for participants who had not started subsequent cancer therapy. For participants who did not progress or who progressed on cancer therapy, PSA progression is defined as the time from randomization to the date of the last PSA level measurement before the start of cancer therapy, if any. Participants who had no on-study PSA level measurements were censored on the day they were randomized. (NCT00744497)
Timeframe: From randomization to date of first PSA measurement leading to confirmed PSA progression (or to last bone scan assessment, if no progression or if cancer therapy started) (maximum reached: 30 months)
| Intervention | Months (Median) |
|---|
| Placebo | 6.9 |
| Dasatinib | 7.2 |
Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval
QTc interval measured by electrocardiogram (ECG). Although a participant may have had several ECGs, only the longest QTc interval was included. (NCT00744497)
Timeframe: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing
| Intervention | Participants (Number) |
|---|
| 0 to 30 msecs increase (n=591, 540) | >30 to 60 msecs increase (n=591, 540) | >60 msecs increase (n=591, 540) | Decrease (n=591, 540) |
|---|
| Dasatinib | 199 | 47 | 26 | 268 |
,| Placebo | 203 | 52 | 32 | 304 |
Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study
BL=baseline; OS=on-study (NCT00744497)
Timeframe: At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated
| Intervention | Participants (Number) |
|---|
| Pericardial effusion at BL/absent OS | Pericardial effusion at BL/present OS | Pericardial effusion at BL/not reported OS | Pericardial effusion absent at BL/ absent OS | Pericardial effusion absent at BL/present OS | Pericardial effusion absent at BL/not reported OS | Pericardial not reported at BL | LVEF OS <40% | LVEF OS >=40% | LVEF not reported OS |
|---|
| Dasatinib | 1 | 1 | 0 | 545 | 26 | 184 | 5 | 2 | 566 | 194 |
,| Placebo | 3 | 0 | 1 | 584 | 24 | 132 | 16 | 2 | 607 | 151 |
Percentage of Participants With 3-year Overall Survival
Survival time was defined to be the length of time from start of study therapy to death due to any cause or until last follow-up (censored value). (NCT00757172)
Timeframe: 3 years
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel + Cisplatin + Panitumumab + RT | 38.6 |
Percentage of Participants With 2-year Disease-free Survival
Disease-free survival was defined as the time from start of study therapy to documentation of disease recurrence. Participants who died without documentation of recurrence were considered to have had tumor recurrence at the time of death unless there was documented evidence that no recurrence occured before death. Participants who failed to return for evaluation after beginning therapy were censored for recurrence on the last day of therapy. Participants who experienced major treatment violations were censored for recurrence on the date the treatment violation occured. (NCT00757172)
Timeframe: 2 years
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel + Cisplatin + Panitumumab + RT | 41.4 |
Number of Participants With Near-complete Response Rate (≤ 10% Residual Cancer in Primary Tumor Viable)
(NCT00757172)
Timeframe: Post surgery
| Intervention | participants (Number) |
|---|
| Docetaxel + Cisplatin + Panitumumab + RT | 11 |
Number of Participants With Pathologic Complete Response Following Surgery
Pathologic complete response (pCR) was defined as no viable residual tumor cells. A cellular residual mucin pools should be noted but also considered a pathologic complete response. (NCT00757172)
Timeframe: Post surgery
| Intervention | participants (Number) |
|---|
| Docetaxel + Cisplatin + Panitumumab + RT | 18 |
Number of Participants With Frequent (>=15% Grade 3/4 Incidence) Adverse Events Regardless of Attribution
Adverse events were assessed by NCI CTCAE (Common Terminology Criteria for Adverse Events) v3.0. Grade 1= mild, grade 2= moderate, grade 3= severe, grade 4= life-threatening; and grade 5= death. (NCT00757172)
Timeframe: Week 1, 3, 5, 7, 9, 4-6 weeks after therapy and within 30 days post surgery
| Intervention | participants (Number) |
|---|
| Hemoglobin | Lymphocytes | Neutrophils | Dehydration | Esophagitis | Nausea |
|---|
| Docetaxel + Cisplatin + Panitumumab + RT | 12 | 30 | 12 | 13 | 13 | 11 |
Progression Free Survival
For determining progression-free survival, progression was determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0). Progression was defined 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. (NCT00771953)
Timeframe: From the date of randomization until the first date that recurrent or progressive disease is objectively documented.
| Intervention | days (Median) |
|---|
| Apricoxib Plus Docetaxel | 75 |
| Placebo Plus Docetaxel | 97 |
| Apricoxib Plus Pemetrexed | 103 |
| Placebo Plus Pemetrexed | 98 |
2-month Progression-free Survival Rate
Evaluation of the 2-month progression-free survival in poor performance status patients with non-squamous non-small cell lung cancer with the goal to improve 2-month progression free survival from 50% to 70%. The 2-month progression free survival is determined after 8 weeks on treatment. Those patients that had less than 20% increase in the tumor target lesions are considered as progression free survival. The primary endpoint is the percentage of patients that are progression free in 2 months. (NCT00801801)
Timeframe: Baseline to 2 months
| Intervention | participants (Number) |
|---|
| Metronomic Taxotere + Nexavar | 4 |
Duration of Confirmed Objective Tumour Response
"The duration of objective response is the time from first documented (CR) or (PR) to the time of progression or death and evaluated according to the modified RECIST criteria version 1.0.~As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.~This endpoint was analysed based on the central independent reviewer as well as the investigator." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | months (Median) |
|---|
| central independent reviewer | investigator assessment |
|---|
| Nintedanib Plus Docetaxel | 4.3 | 5.7 |
,| Placebo Plus Docetaxel | 4.3 | 5.5 |
Duration of Disease Control
"The duration of disease control was defined as the time from randomisation to the date of disease progression or death (which ever occurs first) for patients with disease control.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.~This endpoint was analysed based on the central independent reviewer as well as the investigator." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | months (Median) |
|---|
| central independent reviewer | investigator assessment |
|---|
| Nintedanib Plus Docetaxel | 5.6 | 5.7 |
,| Placebo Plus Docetaxel | 5.6 | 5.6 |
Incidence and Intensity of Adverse Events
"Incidence and intensity of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The worst CTCAE grade per patient is reported and MedDRA version 15.1 used.~Serious signs and symptoms of progressive disease were reported as an adverse event in analysis of this endpoint." (NCT00805194)
Timeframe: From the first drug administration until 28 days after the last drug administration, up to 42 months
| Intervention | % of participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Nitedanib Plus Docetaxel | 5.7 | 16.6 | 21.2 | 33.7 | 16.4 |
,| Placebo Plus Docetaxel | 8.2 | 20.5 | 21.2 | 31.3 | 11.8 |
Objective Tumour Response
"Confirmed objective response is defined as confirmed Complete Response (CR) and Partial Response (PR) and evaluated according to the modified RECIST criteria version 1.0.~As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.~This endpoint was analysed based on the central independent reviewer as well as the investigator." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | % of participants (Number) |
|---|
| central independent reviewer | investigator assessment |
|---|
| Nintedanib Plus Docetaxel | 4.4 | 10.4 |
,| Placebo Plus Docetaxel | 3.3 | 7.6 |
Clinical Improvement
"Clinical improvement was defined as the time from randomisation to deterioration in body weight and/or Eastern Cooperative Oncology group performance score (ECOG PS) whichever occurred first.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | months (Median) |
|---|
| Nitedanib Plus Docetaxel | 5.9 |
| Placebo Plus Docetaxel | 5.2 |
Change From Baseline in Tumour Size
"Percentage change from baseline in tumour size is defined as decrease in the sum of the longest diameter of the target lesion.~Presented means are in fact adjusted best means percentage changes generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)~This endpoint was analysed based on the central independent reviewer as well as the investigator." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | percentage of change in tumor size in mm (Mean) |
|---|
| central independent reviewer | investigator assessment |
|---|
| Nintedanib Plus Docetaxel | -4.87 | -10.34 |
,| Placebo Plus Docetaxel | 0.58 | -2.14 |
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review
"Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | months (Median) |
|---|
| Nintedanib Plus Docetaxel | 3.5 |
| Placebo Plus Docetaxel | 2.7 |
Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator
"Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by investigator according to the modified RECIST (version 1.0) criteria.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | months (Median) |
|---|
| Nintedanib Plus Docetaxel | 4.2 |
| Placebo Plus Docetaxel | 3.0 |
Progression Free Survival (PFS) as Assessed by Central Independent Review
"Progression Free Survival (PFS) as assessed by central independent review according to the modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) . Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier).~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve." (NCT00805194)
Timeframe: From randomisation until cut-off date 2 November 2010 (when 713 PFS events were observed)
| Intervention | months (Median) |
|---|
| Nintedanib Plus Docetaxel | 3.4 |
| Placebo Plus Docetaxel | 2.7 |
Overall Survival (Key Secondary Endpoint)
"Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.~A fixed-sequence-testing was implemented for key secondary endpoint if both the primary and the follow-up analysis showed a treatment benefit (P<0.05) of nintedanib over placebo. In this case, the OS would be tested using hierarchical testing of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013 (approximately 48 months or 1151 deaths among all patients )
| Intervention | months (Median) |
|---|
| Adenocarcinoma and <9 months | Adenocarcinoma | All patients |
|---|
| Nintedanib Plus Docetaxel | 10.9 | 12.6 | 10.1 |
,| Placebo Plus Docetaxel | 7.9 | 10.3 | 9.1 |
Disease Control
"Disease control was defined as a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and evaluated according to the modified RECIST criteria version 1.0.~As per RECIST v1.0 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; 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.~This endpoint was analysed based on the central independent reviewer as well as the investigator." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | % of participants (Number) |
|---|
| central independent reviewer | investigator assessment |
|---|
| Nintedanib Plus Docetaxel | 54.0 | 63.4 |
,| Placebo Plus Docetaxel | 41.3 | 51.4 |
Time to Confirmed Objective Tumour Response
"Time to confirmed objective response is defined as time from randomisation to the date of first documented (CR) or (PR) and evaluated according to the modified RECIST criteria version 1.0.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.~This endpoint was analysed based on the central independent reviewer as well as the investigator." (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | months (Median) |
|---|
| central independent reviewer | investigator assessment |
|---|
| Nintedanib Plus Docetaxel | 1.5 | 2.6 |
,| Placebo Plus Docetaxel | 2.9 | 2.7 |
Quality of Life (QoL)
"Quality of life (QoL) was measured by standardised questionnaires (Health Status Self-Assessment Questionnaire (EQ-5D), EORTC Quality of life questionnaire - Core 30 (EORTC QLQ-C30), Quality of life questionnaire - lung cancer module (EORTC QLQ-LC13). The EORTC QLQ-C30 comprises of 30 questions, using both multi-item scales and single-item measures. EORTC LC-13 comprises of 13 questions incorporating 1 multi-item scale and a series of single items.~The following were the main points of interest:~Time to deterioration of cough (EORTC QLQ-LC13 question 1), Time to deterioration of dyspnoea (QLQ-LC13, composite of questions 3 to 5), Time to deterioration of pain (QLQ- C30, composite of questions 9 and 19).~Time to deterioration of cough, dyspnoea and pain was defined as the time to a 10-point increase from the baseline score.~Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve" (NCT00805194)
Timeframe: From randomisation until cut-off date 15 February 2013
| Intervention | months (Median) |
|---|
| Time to deterioration of cough | Time to deterioration of dyspnoea | Time to deterioration of pain |
|---|
| Nitedanib Plus Docetaxel | 4.3 | 2.0 | 2.8 |
,| Placebo Plus Docetaxel | 3.5 | 2.1 | 2.6 |
Proportion of Patients Experiencing Grade 3 or 4 Diarrhea as Measured by NCI CTCAE v3.0
(NCT00820872)
Timeframe: Up to 10 years
| Intervention | percentage of patients (Number) |
|---|
| Group 1 | 43 |
Complete Pathological Response (pCR) Rate in Breast and Axilla According to the Miller&Payne Criteria (G5-A and G5-D).
Within 3-4 weeks after last docetaxel dose the surgery was performed to evaluate pathological response. According to the Miller&Payne Criteria, pCR in node-negative patients is a grade 5-A and in node-positive patients is a grade 5-D. (NCT00841828)
Timeframe: Up to 16 weeks
| Intervention | percentage of participants with pCR (Number) |
|---|
| Arm 1: EC -> D + Lapatinib | 23.5 |
| Arm 2: EC -> D + Trastuzumab | 47.9 |
Overall Clinical Response Rate (ORR)
"Overall clinical response was evaluated according to the Response Evaluation Criteria in Solid Tumours (RECIST) criteria (Therasse et al, 2000). Is defined as the sum of Complete responses plus Partial responses.~It was evaluated after the fourth EC cycle and before surgery using ultrasound, mammography, or MRI." (NCT00841828)
Timeframe: Up to 12 weeks
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: EC -> D + Lapatinib | 62.7 |
| Arm 2: EC -> D + Trastuzumab | 77.1 |
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)
| Intervention | nmol/L (Mean) |
|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | 24.9 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | 40.6 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | 1.36 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | 4.67 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | 2.21 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | 17.1 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | 2.27 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | 3.80 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | 3.24 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | 23.8 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | 36.8 |
| MK-2206 135 mg QW+Erlotinib 100 mg | 96.6 |
| MK-2206 135 mg QW+Erlotinib 150 mg | 95.5 |
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)
| Intervention | mg (Number) |
|---|
| MK-2206 Administered Q3W+Carboplatin+Paclitaxel | NA |
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)
| Intervention | mg (Number) |
|---|
| MK-2206 Administered QW+Erlotinib | NA |
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)
| Intervention | mg (Number) |
|---|
| MK-2206 Administered Q3W+Docetaxel | NA |
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)
| Intervention | mg (Number) |
|---|
| MK-2206 Administered QOD+Docetaxel | NA |
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)
| Intervention | mg (Number) |
|---|
| MK-2206 Administered QOD+Erlotinib | NA |
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)
| Intervention | Participants (Count of Participants) |
|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | 1 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | 2 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | 1 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | 1 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | 2 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | 3 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | 0 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | 0 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | 1 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | 2 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | 1 |
| MK-2206 135 mg QW+Erlotinib 100 mg | 0 |
| MK-2206 135 mg QW+Erlotinib 150 mg | 1 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | 1 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | 3 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | 0 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | 1 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | 1 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | 0 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | 0 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | 0 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | 0 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | 0 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | 0 |
| MK-2206 135 mg QW+Erlotinib 100 mg | 0 |
| MK-2206 135 mg QW+Erlotinib 150 mg | 0 |
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)
| Intervention | hours (Median) |
|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | 4.0 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | 8.0 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | 6.0 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | 10.0 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | 5.0 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | 6.0 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | 4.0 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | 6.0 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | 6.0 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | 6.0 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | 7.0 |
| MK-2206 135 mg QW+Erlotinib 100 mg | 6.0 |
| MK-2206 135 mg QW+Erlotinib 150 mg | 4.0 |
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)
| Intervention | nmol•hr/L (Mean) |
|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | 1630 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | 2700 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | 4130 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | 7420 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | 9730 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | 1320 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | 3000 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | 8090 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | 7690 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | 1460 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | 2110 |
| MK-2206 135 mg QW+Erlotinib 100 mg | 6420 |
| MK-2206 135 mg QW+Erlotinib 150 mg | 6560 |
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)
| Intervention | nmol/L (Mean) |
|---|
| MK-2206 45 mg QOD+Carboplatin+Paclitaxel | 57.7 |
| MK-2206 60 mg QOD+Carboplatin+Paclitaxel | 88.3 |
| MK-2206 90 mg Q3W+Carboplatin+Paclitaxel | 144 |
| MK-2206 135 mg Q3W+Carboplatin+Paclitaxel | 247 |
| MK-2206 200 mg Q3W+Carboplatin+Paclitaxel | 431 |
| MK-2206 45 mg QOD+Docetaxel 75 mg/m^2 | 42.9 |
| MK-2206 90 mg Q3W+Docetaxel 60 mg/m^2 | 106 |
| MK-2206 135 mg Q3W+Docetaxel 60 mg/m^2 | 278 |
| MK-2206 200 mg Q3W+Docetaxel 60 mg/m^2 | 287 |
| MK-2206 45 mg QOD+Erlotinib 100 mg | 48.8 |
| MK-2206 45 mg QOD+Erlotinib 150 mg | 65.6 |
| MK-2206 135 mg QW+Erlotinib 100 mg | 212 |
| MK-2206 135 mg QW+Erlotinib 150 mg | 244 |
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)
| Intervention | mg (Number) |
|---|
| MK-2206 Administered QOD+Carboplatin+Paclitaxel | NA |
Time to PSA Progression
Time to PSA pregression is defined as the time at which therapy statred and ends when the PSA increased by 50% above the nadir confirmed on a second determination. (NCT00861471)
Timeframe: up to 2 years
| Intervention | days (Mean) |
|---|
| Docetaxel +Gleevec | 188 |
Percentage of Participants With Greater or Equal to 80% PSA Reduction From Baseline Without Clinical or Radiologic Evidence of Progression
PSA was measured at baseline on day 1/cycle 1 before treatment, then day 1 of every cycle afterwards during therapy. (NCT00861471)
Timeframe: up to 9 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel +Gleevec | 16 |
Percentage of Participants With Measurable Disease Response
Measurable disease response is defined as the number of participants whose best response is complete response or partial response over the number of patients with measurable desease according to the Response Evaluation Criteria in Solid Tumors (RECIST). (NCT00861471)
Timeframe: up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel +Gleevec | 20 |
Percentage of Participants With Prostate Specific Antigen (PSA) Response
PSA response is defined as a greater than or equal to a 50% decrease in PSA from the baseline without clinical or radiologic evidence of progression according to the Response Evaluation Criteria in Solid Tumors (RECIST). PSA concentration was measured at baseline on day 1/cycle 1 before treatment, then day 1 of every cycle afterwards during therapy. (NCT00861471)
Timeframe: up to 9 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel +Gleevec | 50 |
Positive Aldo-keto Reductase 1C3 (AKR1C3) Expression in Participating Patients
"AKR1C3 was evaluated on a semi-quantitative scale, and the percentage of cells staining at each of the following four levels was recorded: 0 (unstained), 1+ (weak staining), 2+ (moderate staining) and 3+ (strong staining).~Patients with a strong staining score (3+) were considered to be AKR1C3 positive" (NCT00862134)
Timeframe: Within 1 year of enrollment
| Intervention | participants (Number) |
|---|
| Docetaxel | 5 |
| PR104 + Docetaxel | 8 |
Safety and Tolerability: Serious Adverse Events
The number of participants with at least one Serious Adverse Event was measured. (NCT00862134)
Timeframe: 30 days following last administration of study treatment
| Intervention | participants (Number) |
|---|
| Docetaxel | 8 |
| PR104 + Docetaxel | 5 |
Number of Participants That Achieved a Response (Complete or Partial) After Receiving PR104/Docetaxel Versus Docetaxel Alone
Defined as the number of subjects with complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors (RECIST) criteria (NCT00862134)
Timeframe: Participants were followed for the duration on study, an average of 4 months
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) |
|---|
| Docetaxel | 0 | 1 |
,| PR104 + Docetaxel | 0 | 3 |
Progression Free Survival (PFS)
From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. (NCT00872989)
Timeframe: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years
| Intervention | months (Median) |
|---|
| Arm I: Docetaxel | 3.5 |
| Arm II: Docetaxel + Vandetanib | 3.0 |
Overall Survival
From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact. (NCT00872989)
Timeframe: every 3 months for two years and then every 6 months for 3 years
| Intervention | months (Median) |
|---|
| Arm I: Docetaxel | 18 |
| Arm II: Docetaxel + Vandetanib | 14 |
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease After Treatment With Single Agent Vandetanib Following Progression on Single Agent Docetaxel
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 in conjunction with measured CA125 responses (NCT00872989)
Timeframe: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Unconfirmed Complete Response | Unconfirmed Partial Response | Stable/No Response | Increasing Disease | Assessment Inadequate |
|---|
| Vandetanib | 0 | 0 | 0 | 1 | 8 | 20 | 1 |
Number of Participants With a Complete Response, Partial Response, Stable Disease, or Increasing Disease
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 in conjunction with measured CA125 responses (NCT00872989)
Timeframe: Disease assessment for responses were performed every 6 weeks for as long as the patient remained on protocol treatment, up to 5 years.
| Intervention | participants (Number) |
|---|
| Complete Response | Partial Response | Unconfirmed Complete Response | Unconfirmed Partial Response | Stable/No Response | Increasing Disease | Symptomatic Deterioration | Assessment Inadequate |
|---|
| Arm I: Docetaxel | 0 | 5 | 1 | 2 | 19 | 23 | 0 | 7 |
,| Arm II: Docetaxel + Vandetanib | 0 | 6 | 0 | 2 | 17 | 20 | 1 | 6 |
Time to Treatment Failure
Time to treatment failure after treatment with single agent vandetanib following progression on single agent docetaxel. Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years. (NCT00872989)
Timeframe: Disease assessments were performed every 6 weeks for as long as the patient remained on protocol, up to 5 years.
| Intervention | Months (Median) |
|---|
| Vandetanib | 1.4 |
Clinical Relevant Abnormalities in Laboratory Parameters
Number of participants with clinically relevant abnormalities in laboratory parameters reported as adverse events (NCT00876460)
Timeframe: Between the first administration of docetaxel and 28 days after last administration of docetaxel and/or nintedanib, up to 1367 days
| Intervention | Participants (Number) |
|---|
| Alanine aminotransferase increased | Aspartate aminotransferase increased | Blood alkaline phosphatase increased | Gamma-glutamyltransferase increased | Blood bilirubin increased | Platelet count decreased | White blood cell count decreased | Blood calcium decreased | Gamma-glutamyltransferase | Blood chloride decreased | Blood thyroid stimulating hormone increased | Blood urea increased | C-reactive protein increased | Haemoglobin decreased | Lymphocyte count decreased | Neutrophil count decreased | Prothrombin level decreased | Tri-iodothyronine free decreased | Blood albumin decreased | Blood potassium decreased | Blood uric acid increased | Blood urine | Blood urine present | Electrocardiogram QT prolonged |
|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | 2 | 2 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | 4 | 4 | 3 | 4 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
,| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | 5 | 5 | 4 | 4 | 0 | 3 | 3 | 0 | 2 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | 4 | 4 | 4 | 4 | 1 | 0 | 2 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 |
,| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | 3 | 3 | 3 | 3 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | 4 | 4 | 2 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | 5 | 5 | 3 | 4 | 0 | 0 | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
AUC0-inf of Docetaxel in Course 2
"AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of docetaxel in course 2.~Docetaxel 50 mg/m2 patients were assigned to Docetaxel 60 mg/m2 in Cycle 1, but the dose was reduced to 50 mg/m2 in Cycle 2 as defined in the Clinical Trial Protocol." (NCT00876460)
Timeframe: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Docetaxel 50 mg/m2 | 2320 |
| Docetaxel 60 mg/m2 | 3750 |
| Docetaxel 75 mg/m2 | 4270 |
Cmax of Docetaxel in Course 1
Cmax (maximum measured plasma concentration) after the first administration of docetaxel in course 1 (NCT00876460)
Timeframe: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
| Intervention | ng/mL (Geometric Mean) |
|---|
| Docetaxel 60 mg/m2 | 3150 |
| Docetaxel 75 mg/m2 | 3550 |
AUC0-inf of Nintedanib in Course 1
AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of nintedanib in course 1 (NCT00876460)
Timeframe: -0:05 hours (h) before drug administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23:55h after drug administration in course 1
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Nintedanib 100 mg | 169 |
| Nintedanib 150 mg | 260 |
| Nintedanib 200 mg | 349 |
Objective Tumor Response
Number of participants with objective response defined as complete response (CR) or partial response (PR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) version 1.0 (NCT00876460)
Timeframe: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
| Intervention | Participants (Number) |
|---|
| Yes | No |
|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | 0 | 3 |
,| Nintedanib 150 mg + Docetaxel 60 mg/m2 | 2 | 7 |
,| Nintedanib 150 mg + Docetaxel 75 mg/m2 | 5 | 7 |
,| Nintedanib 200 mg + Docetaxel 60 mg/m2 | 2 | 6 |
,| Nintedanib 200 mg + Docetaxel 75 mg/m2 | 1 | 5 |
Disease Control
Number of participants with disease control, defined as complete response (CR) or partial response (PR) or stable disease (SD) according to the Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 (NCT00876460)
Timeframe: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
| Intervention | Participants (Number) |
|---|
| Yes | No |
|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | 2 | 1 |
,| Nintedanib 150 mg + Docetaxel 60 mg/m2 | 5 | 4 |
,| Nintedanib 150 mg + Docetaxel 75 mg/m2 | 12 | 0 |
,| Nintedanib 200 mg + Docetaxel 60 mg/m2 | 5 | 3 |
,| Nintedanib 200 mg + Docetaxel 75 mg/m2 | 4 | 2 |
Time to Treatment Failure (TTF)
"For participants with known date of discontinuation of the study treatment (or progression [not necessarily confirmed by tumour imaging; can also be based on any clinical sign of tumour progression] or death): TTF [days] = earlier of date of discontinuation of the study treatment, progression, or death - date the study treatment started + 1.~For participants known to be alive without progression by the end of trial or follow-up visit: TTF (censored) [days] = date when the patient is known to be progression-free and alive - date the study treatment started + 1.~Progression is assessed according to RECIST version 1.0." (NCT00876460)
Timeframe: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
| Intervention | Days (Median) |
|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | 200.0 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 | 83.5 |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 | 134.0 |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 | 87.0 |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 | 176.0 |
Progression-Free Survival (PFS)
"For participants with known date of progression or death (of any cause): PFS [days] = earlier of date of progression or death - date the study treatment started + 1.~For participants known to be alive without progression by the end of trial or follow-up visit: PFS (censored) [days] = date of last imaging when the participant is known to be progression-free and alive - date the study treatment started + 1.~Progression is assessed according to RECIST version 1.0." (NCT00876460)
Timeframe: Pre-treatment, every 6 weeks from treatment course 3, end of treatment (up to 1367 days)
| Intervention | Days (Median) |
|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | 229.5 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 | 117.0 |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 | 139.0 |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 | 351.0 |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 | 184.0 |
Number of Participants Who Experienced Dose Limited Toxicity in Combination Therapy of Nintedanib and Docetaxel
"Number of participants experienced Dose Limited Toxicity (DLT) in combination therapy of nintedanib and docetaxel.~Maximum tolerated dose (MTD) of nintedanib combination with docetaxel were to be determined separately in the patient groups of body surface area (BSA) <1.5 m2 and BSA ≥1.5 m2. The MTD were to be determined as a combination of a dose equal to or less than 200 mg b.i.d. of nintedanib and 60 mg/m2 and 75 mg/m2 every 3 weeks of docetaxel at which either 0 out of 3, 1 out of 6, or 2 out of 6 patients experienced DLT." (NCT00876460)
Timeframe: During the first treatment course, up to 3 weeks
| Intervention | Participants (Number) |
|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | 0 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | 2 |
| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | 0 |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | 1 |
| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | 2 |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | 3 |
| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | 2 |
| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | 2 |
Cmax of Nintedanib in Course 1
Cmax (maximum measured plasma concentration) after the first administration of nintedanib in course 1 (NCT00876460)
Timeframe: -0:05h before drug administration and 1h, 2h, 3h, 4h, 6h, 7h, 10h and 23:55h after drug administration in course 1
| Intervention | ng/mL (Geometric Mean) |
|---|
| Nintedanib 100 mg | 29.3 |
| Nintedanib 150 mg | 33.4 |
| Nintedanib 200 mg | 59.9 |
Adverse Events According to Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 for All Courses
"Number of participants with adverse events according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 for all courses.~The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE)." (NCT00876460)
Timeframe: Between the first administration of docetaxel and 28 days after last administration of docetaxel and/or nintedanib, up to 1367 days
| Intervention | Participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Nintedanib 100 mg + Docetaxel 60 mg/m2 | 0 | 0 | 0 | 3 | 0 |
,| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | 0 | 0 | 1 | 6 | 0 |
,| Nintedanib 150 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | 0 | 0 | 2 | 1 | 0 |
,| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA <1.5 m^2) | 0 | 0 | 0 | 5 | 1 |
,| Nintedanib 150 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | 0 | 0 | 0 | 7 | 0 |
,| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA <1.5 m^2) | 0 | 0 | 0 | 3 | 0 |
,| Nintedanib 200 mg + Docetaxel 60 mg/m2 (BSA >=1.5 m^2) | 0 | 0 | 1 | 5 | 1 |
,| Nintedanib 200 mg + Docetaxel 75 mg/m2 (BSA >=1.5 m^2) | 0 | 0 | 0 | 6 | 0 |
Cmax of Docetaxel in Course 2
"Cmax (maximum measured plasma concentration) after the first administration of docetaxel in course 2.~Docetaxel 50 mg/m2 patients were assigned to Docetaxel 60 mg/m2 in Cycle 1, but the dose was reduced to 50 mg/m2 in Cycle 2 as defined in the Clinical Trial Protocol." (NCT00876460)
Timeframe: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
| Intervention | ng/mL (Geometric Mean) |
|---|
| Docetaxel 50 mg/m2 | 1870 |
| Docetaxel 60 mg/m2 | 3740 |
| Docetaxel 75 mg/m2 | 4070 |
AUC0-inf of Docetaxel in Course 1
AUC0-inf (area under the plasma concentration-time curve over the time interval from 0 extrapolated to infinity) after the first administration of docetaxel in course 1 (NCT00876460)
Timeframe: -0:05h before drug administration and 1h, 1.5h, 2h, 3h, 4h, 7h, 23:55h and 47:55h after drug administration
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Docetaxel 60 mg/m2 | 3270 |
| Docetaxel 75 mg/m2 | 3810 |
Grade 3-5 Toxicity Rate
Grade 3-5 toxicity rate is the percentage of participants experiencing maximum grade of all toxicity types of grade 3-5 with any attribution on treatment during the randomized phase. (NCT00880334)
Timeframe: Assessed each cycle throughout treatment from time of first dose and up to day 30 post-treatment. Median treatment duration for this study cohort approximated 2 cycles (range 1-31).
| Intervention | percentage of participants (Number) |
|---|
| Vandetanib and Docetaxel | 73 |
| Placebo and Docetaxel | 57 |
Disease Control Rate
Disease control rate is defined as the percentage of participants with confirmed overall Stable Disease (SD) or better using RECIST 1.0 criteria which parallels absence of disease progression (PD) on treatment during the randomized phase. Per RECIST 1.0 for target lesions, PD is at least a 20% increase in sum LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or appearance of new lesions. For non-target lesions, PD is the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. Patients without measurable disease only at baseline are included, based on status of non-target lesions. (NCT00880334)
Timeframe: Disease evaluations occurred at week 6 and 12 and thereafter every 3 cycles/9 weeks on treatment. Median treatment duration for this study cohort approximated 2 cycles (range 1-31).
| Intervention | percentage of participants (Number) |
|---|
| Vandetanib and Docetaxel | 51 |
| Placebo and Docetaxel | 42 |
Objective Response Rate
Objective response rate is defined as the percentage of participants who achieved a confirmed overall partial response (PR) or complete response (CR) using RECIST criteria on treatment during the randomized phase. Patients without measurable disease only at baseline are included, based on status of non-target lesions.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. (NCT00880334)
Timeframe: Disease evaluations occurred at week 6 and 12 and thereafter every 3 cycles/9 weeks on treatment. Median treatment duration for this study cohort approximated 2 cycles (range 1-31).
| Intervention | percentage of participants (Number) |
|---|
| Vandetanib and Docetaxel | 7.1 |
| Placebo and Docetaxel | 11.1 |
Febrile Neutropenia
The primary endpoint of the study was safety, as reflected by a febrile neutropenia rate of <10%. (NCT00883675)
Timeframe: 2 months
| Intervention | participants (Number) |
|---|
| Treatment | 12 |
Overall Objective Response
Overall Objective Response will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) guideline (version 1.1) (NCT00887809)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progression of Disease (POD) |
|---|
| Gemcitabine, Docetaxel, Bevacizumab | 0 | 9 | 23 | 1 |
,| Gemcitabine, Docetaxel, Placebo | 1 | 1 | 7 | 1 |
Alive and Progression-Free at 6 Months
Percentage of patients alive and progression-free at 6 months (NCT00890825)
Timeframe: 6 months after first dose of treatment
| Intervention | percentage (Number) |
|---|
| AZD6244 + Docetaxel | 37.1 |
| Placebo + Docetaxel | 15.8 |
Change From Baseline in Tumour Size at 6 Week.
Percentage change from baseline in tumour size at 6 week. Values calculated as tumour sizes at 6 weeks minus value at baseline. (NCT00890825)
Timeframe: 6 weeks after first dose of treatment
| Intervention | Percentage change from baseline (Least Squares Mean) |
|---|
| AZD6244 + Docetaxel | -16.98 |
| Placebo + Docetaxel | 0.05 |
Change From Baseline in Tumour Size at Week 12
Percentage change from baseline in tumour size at Week 12. Values calculated as tumour sizes at 12 weeks minus value at baseline. (NCT00890825)
Timeframe: 12 weeks
| Intervention | Percent change from baseline (Least Squares Mean) |
|---|
| AZD6244 + Docetaxel | -19.38 |
| Placebo + Docetaxel | 6.62 |
Duration of Response
Duration of response is 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 should coincide with the date of progression or death from any cause used for the PFS endpoint. (NCT00890825)
Timeframe: At least 12 months after start of treatment
| Intervention | Days (Mean) |
|---|
| AZD6244 + Docetaxel | 193.4 |
| Placebo + Docetaxel | NA |
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)
| Intervention | months (Median) |
|---|
| M0 (non-metastatic lesion) | M1 (metastatic lesion) |
|---|
| Chemoradiation for Nasopharyngeal Carcinoma | 79 | 76 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Chemoradiation for Nasopharyngeal Carcinoma | 1 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| M0 (non-metastatic lesion) | M1 (metastatic lesion) |
|---|
| Chemoradiation for Nasopharyngeal Carcinoma | 18 | 4 |
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)
| Intervention | Participants (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 Carcinoma | 17 | 3 | 0 | 0 | 3 | 1 | 0 | 0 |
Best Response
Best response on treatment was based on RECIST 1.0 criteria: Complete Response (CR) is complete disappearance of all target lesions; 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. Both require confirmation no fewer than 4 weeks apart. CR/PR assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions. Progressive disease (PD) is at least a 20% increase in the sum of longest diameter of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. Stable disease is defined as any condition not meeting above criteria. (NCT00911820)
Timeframe: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment duration was a median of 5 cycles (up to approximately 1 year) in this study cohort as of this analysis..
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Removed Before Restaging |
|---|
| Arm A: PCA | 3 | 22 | 15 | 1 | 3 |
,| Arm B: TPCA | 0 | 21 | 14 | 0 | 6 |
7-month Progression-Free Survival
7-month progression-free survival is the probability of patients remaining alive and progression-free at 7-months from study entry estimated using Kaplan-Meier methods. Per RECIST 1.0 criteria: progressive disease (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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. (NCT00911820)
Timeframe: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Relevant for this endpoint was disease status at 7 months of follow-up.
| Intervention | probability (Number) |
|---|
| Arm A: PCA | 0.581 |
| Arm B: TPCA | 0.582 |
Overall Response (OR) Rate
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. (NCT00911820)
Timeframe: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Treatment duration was a median of 5 cycles (up to approximately 1 year) in this study cohort as of this analysis.
| Intervention | proportion of patients (Number) |
|---|
| Arm A: PCA | .568 |
| Arm B: TPCA | .512 |
Overall Survival
Overall survival is defined as the time from study entry to death or date last known alive and estimate using Kaplan-Meier (KM) methods. (NCT00911820)
Timeframe: Patients in the study cohort were followed up to approximately 2.5 years as of this analysis.
| Intervention | months (Median) |
|---|
| Arm A: PCA | 11.7 |
| Arm B: TPCA | 13.4 |
Progression-Free Survival
Progression-free survival based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Patients alive and progression-free at last follow-up are censored. Per RECIST 1.0 criteria: progressive disease 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. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. (NCT00911820)
Timeframe: Disease was evaluated radiologically at baseline and every 2 cycles on treatment; Patients were followed for up to 2.5 years as of this analysis.
| Intervention | months (Median) |
|---|
| Arm A: PCA | 7.9 |
| Arm B: TPCA | 8.4 |
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)
| Intervention | Microgram per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 Day 1 (in absence of trastuzumab) | Cycle 2 Day 1 (in presence of trastuzumab) |
|---|
| Trastuzumab + Docetaxel + Carboplatin | 51 | 52 |
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 + Carboplatin | 9 | 9 |
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 + Carboplatin | 19 | 21 |
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)
| Intervention | msec (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 + Carboplatin | 3.5 | -9.3 | -4.3 | -15.6 | -13.4 | 3.9 | -0.8 | 1.4 | -13.2 | -14.2 | -0.1 | 1.4 | 4.2 | 9.7 | 13.7 | -0.1 | -1.8 | -1.8 | -0.5 | -0.3 |
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)
| Intervention | beats 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 + Carboplatin | 0.5 | 9.6 | 6.2 | 3.1 | -0.7 |
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)
| Intervention | ratio (Geometric Mean) |
|---|
| Trastuzumab + Docetaxel + Carboplatin | 1.02 |
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)
| Intervention | ratio (Geometric Mean) |
|---|
| Trastuzumab + Docetaxel + Carboplatin | 1.07 |
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
| Intervention | milliseconds (msec) (Mean) |
|---|
| Trastuzumab + Docetaxel + Carboplatin | -8.4 |
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
| Intervention | msec (Mean) |
|---|
| Trastuzumab + Docetaxel + Carboplatin | -5.9 |
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)
| Intervention | participants (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 + Carboplatin | 0 | 2 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 2 | 4 | 1 | 2 | 4 | 1 |
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)
| Intervention | Hour*microgram/milliliter (hr*mcg/mL) (Mean) |
|---|
| Cycle 1 Day 1 (in absence of trastuzumab) | Cycle 2 Day 1 (in presence of trastuzumab) |
|---|
| Trastuzumab + Docetaxel + Carboplatin | 115 | 123 |
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)
| Intervention | hr (Mean) |
|---|
| Cycle 1 Day 1 (in absence of trastuzumab) (n=44) | Cycle 2 Day 1 (in presence of trastuzumab) (n=43) |
|---|
| Trastuzumab + Docetaxel + Carboplatin | 2 | 2 |
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)
| Intervention | participants (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 + Carboplatin | 44 | 4 | 1 | 0 | 49 | 1 | 0 | 0 | 48 | 2 | 0 | 0 | 48 | 0 | 0 | 0 | 48 | 0 | 0 | 0 | 36 | 10 | 2 | 1 | 41 | 7 | 2 | 0 | 39 | 9 | 2 | 0 | 43 | 4 | 1 | 0 | 43 | 5 | 0 | 0 |
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)
| Intervention | participants (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 + Carboplatin | 0 | 0 | 0 | 0 | 0 |
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)
| Intervention | participants (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 + Carboplatin | 0 | 0 | 0 | 0 | 0 |
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)
| Intervention | participants (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 + Carboplatin | 49 | 0 | 0 | 50 | 0 | 0 | 50 | 0 | 0 | 48 | 0 | 0 | 48 | 0 | 0 | 49 | 0 | 0 | 50 | 0 | 0 | 49 | 1 | 0 | 48 | 0 | 0 | 48 | 0 | 0 |
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)
| Intervention | participants (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 + Carboplatin | 0 | 4 | 0 | 0 | 4 | 0 | 0 | 4 | 0 | 0 | 4 | 0 | 0 | 4 | 0 |
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
| Intervention | mcg/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 + Carboplatin | 0.178 | 38.8 | 38.7 | 29.7 |
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
| Intervention | mcg/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 + Carboplatin | 146.3 | 187.1 | 179.1 | 181.5 |
Overall Survival (OS)
OS: Time in months from randomization to date of death due to any cause. OS was calculated as (the death date minus the date of randomization plus 1) divided by 30.4. (NCT00932893)
Timeframe: Randomization until death (up to 4.5 years)
| Intervention | months (Median) |
|---|
| Crizotinib | 21.7 |
| Chemotherapy | 21.9 |
Percentage of Participants With Disease Control at Week 12
Disease control: participants with CR, PR, or SD according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least 30 % decrease in 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. 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 (including an absolute increase of at least 5 mm) 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. (NCT00932893)
Timeframe: Week 12
| Intervention | percentage of participants (Number) |
|---|
| Crizotinib | 64.2 |
| Chemotherapy | 38.5 |
Percentage of Participants With Disease Control at Week 6
Disease control: participants with CR, PR, or stable disease (SD) according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least 30 % decrease in 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. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. PD: at least a 20% increase (including an absolute increase of at least 5 mm) 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. Disease control is based on independent radiology review. (NCT00932893)
Timeframe: Week 6
| Intervention | percentage of participants (Number) |
|---|
| Crizotinib | 81.5 |
| Chemotherapy | 55.2 |
Percentage of Participants With Objective Response (OR)
Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 millimeter [mm] short axis). PR: at least 30 percent (%) decrease in 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. Objective response is based on independent radiology review. (NCT00932893)
Timeframe: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Crizotinib | 65.3 |
| Chemotherapy | 19.5 |
Progression-Free Survival (PFS)
PFS: Time in months from randomization to first documentation of objective disease progression as determined by independent radiology review or to death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of randomization plus 1) divided by 30.4. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria version 1.1 (RECIST v1.1), as at least a 20% increase (including an absolute increase of at least 5 mm) 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. (NCT00932893)
Timeframe: Randomization until progressive disease (PD) or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)
| Intervention | months (Median) |
|---|
| Crizotinib | 7.7 |
| Chemotherapy | 3.0 |
Time to Tumor Response (TTR)
Time from date of randomization to first documentation of objective tumor response. TTR was calculated for the subgroup of participants with objective tumor response. Objective tumor response was defined as CR or PR according to RECIST v1.1. CR: disappearance of all target and non-target lesions and normalization of tumor marker level, all lymph nodes must be non-pathological in size (<10 mm short axis). PR: at least 30 % decrease in 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. (NCT00932893)
Timeframe: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)
| Intervention | weeks (Median) |
|---|
| Crizotinib | 6.3 |
| Chemotherapy | 12.6 |
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
EORTC QLQ-C30: included global health status/quality of life (QoL), functional scales (physical, role, cognitive, emotional, and social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, 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 for Global Qol/functional scales=better level of QoL/functioning or higher score for symptom scale=greater degree of symptoms. (NCT00932893)
Timeframe: Baseline, Day (D) 1 of each cycle (C) until disease progression, end of treatment (EOT, up to 112 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Global QoL: Baseline (n=165, 162) | Global QoL: C2D1 (n=154, 133) | Global QoL: C3D1 (n=154, 106) | Global QoL: C4D1 (n=135, 90) | Global QoL: C5D1 (n=123, 74) | Global QoL: C6D1 (n=120, 70) | Global QoL: C7D1 (n=114, 52) | Global QoL: C8D1 (n=110, 43) | Global QoL: C9D1 (n=101, 37) | Global QoL: C10D1 (n=94, 33) | Global QoL: C11D1 (n=83, 25) | Global QoL: C12D1 (n=76, 23) | Global QoL: C13D1 (n=74, 21) | Global QoL: C14D1 (n=66, 19) | Global QoL: C15D1 (n=62, 16) | Global QoL: C16D1 (n=53, 12) | Global QoL: C17D1 (n=47, 11) | Global QoL: C18D1 (n=44, 11) | Global QoL: C19D1 (n=40, 9) | Global QoL: C20D1 (n=35, 8) | Global QoL: C21D1 (n=30, 8) | Global QoL: C22D1 (n=24, 7) | Global QoL: C23D1 (n=23, 4) | Global QoL: C24D1 (n=20, 3) | Global QoL: C25D1 (n=18, 3) | Global QoL: C26D1 (n=14, 3) | Global QoL: C27D1 (n=14, 2) | Global QoL: C28D1 (n=11, 2) | Global QoL: C29D1 (n=8, 2) | Global QoL: C30D1 (n=8, 1) | Global QoL: C31D1 (n=7, 0) | Global QoL: C32D1 (n=6, 0) | Global QoL: C33D1 (n=6, 0) | Global QoL: C34D1 (n=5, 0) | Global QoL: C35D1 (n=4, 0) | Global QoL: C36D1 (n=1, 0) | Global QoL: C37D1 (n=1, 0) | Physical Functioning: Baseline (n=165, 163) | Physical Functioning: C2D1 (n=155, 133) | Physical Functioning: C3D1 (n=154, 106) | Physical Functioning: C4D1 (n=135, 91) | Physical Functioning: C5D1 (n=123, 74) | Physical Functioning: C6D1 (n=120, 70) | Physical Functioning: C7D1 (n=115, 52) | Physical Functioning: C8D1 (n=111, 43) | Physical Functioning: C9D1 (n=101, 37) | Physical Functioning: C10D1 (n=94, 33) | Physical Functioning: C11D1 (n=84, 25) | Physical Functioning: C12D1 (n=76, 23) | Physical Functioning: C13D1 (n=74, 21) | Physical Functioning: C14D1 (n=66, 19) | Physical Functioning: C15D1 (n=62, 16) | Physical Functioning: C16D1 (n=53, 12) | Physical Functioning: C17D1 (n=47, 11) | Physical Functioning: C18D1 (n=45, 11) | Physical Functioning: C19D1 (n=40, 9) | Physical Functioning: C20D1 (n=35, 8) | Physical Functioning: C21D1 (n=30, 8) | Physical Functioning: C22D1 (n=24, 7) | Physical Functioning: C23D1 (n=23, 4) | Physical Functioning: C24D1 (n=20, 3) | Physical Functioning: C25D1 (n=18, 3) | Physical Functioning: C26D1 (n=14, 3) | Physical Functioning: C27D1 (n=14, 2) | Physical Functioning: C28D1 (n=11, 2) | Physical Functioning: C29D1 (n=8, 2) | Physical Functioning: C30D1 (n=8, 1) | Physical Functioning: C31D1 (n=7, 0) | Physical Functioning: C32D1 (n=6, 0) | Physical Functioning: C33D1 (n=6, 0) | Physical Functioning: C34D1 (n=5, 0) | Physical Functioning: C35D1 (n=4, 0) | Physical Functioning: C36D1 (n=1, 0) | Physical Functioning: C37D1 (n=1, 0) | Role Functioning: Baseline (n=165, 163) | Role Functioning: C2D1 (n=155, 133) | Role Functioning: C3D1 (n=154, 106) | Role Functioning: C4D1 (n=134, 91) | Role Functioning: C5D1 (n=123, 74) | Role Functioning: C6D1 (n=120, 70) | Role Functioning: C7D1 (n=115, 52) | Role Functioning: C8D1 (n=111, 43) | Role Functioning: C9D1 (n=101, 37) | Role Functioning: C10D1 (n=94, 33) | Role Functioning: C11D1 (n=84, 25) | Role Functioning: C12D1 (n=76, 23) | Role Functioning: C13D1 (n=74, 21) | Role Functioning: C14D1 (n=66, 19) | Role Functioning: C15D1 (n=62, 16) | Role Functioning: C16D1 (n=53, 12) | Role Functioning: C17D1 (n=47, 11) | Role Functioning: C18D1 (n=45, 11) | Role Functioning: C19D1 (n=40, 9) | Role Functioning: C20D1 (n=35, 8) | Role Functioning: C21D1 (n=30, 8) | Role Functioning: C22D1 (n=24, 7) | Role Functioning: C23D1 (n=23, 4) | Role Functioning: C24D1 (n=20, 3) | Role Functioning: C25D1 (n=18, 3) | Role Functioning: C26D1 (n=14, 3) | Role Functioning: C27D1 (n=14, 2) | Role Functioning: C28D1 (n=11, 2) | Role Functioning: C29D1 (n=8, 2) | Role Functioning: C30D1 (n=8, 1) | Role Functioning: C31D1 (n=7, 0) | Role Functioning: C32D1 (n=6, 0) | Role Functioning: C33D1 (n=6, 0) | Role Functioning: C34D1 (n=5, 0) | Role Functioning: C35D1 (n=4, 0) | Role Functioning: C36D1 (n=1, 0) | Role Functioning: C37D1 (n=1, 0) | Emotional Functioning: Baseline (n=165, 162) | Emotional Functioning: C2D1 (n=155, 133) | Emotional Functioning: C3D1 (n=154, 106) | Emotional Functioning: C4D1 (n=135, 90) | Emotional Functioning: C5D1 (n=123, 74) | Emotional Functioning: C6D1 (n=120, 70) | Emotional Functioning: C7D1 (n=115, 52) | Emotional Functioning: C8D1 (n=111, 43) | Emotional Functioning: C9D1 (n=101, 37) | Emotional Functioning: C10D1 (n=94, 33) | Emotional Functioning: C11D1 (n=84,25) | Emotional Functioning: C12D1 (n=76, 23) | Emotional Functioning: C13D1 (n=74, 21) | Emotional Functioning: C14D1 (n=66, 19) | Emotional Functioning: C15D1 (n=62, 16) | Emotional Functioning: C16D1 (n=53, 12) | Emotional Functioning: C17D1 (n=47, 11) | Emotional Functioning: C18D1 (n=44, 11) | Emotional Functioning: C19D1 (n=40, 9) | Emotional Functioning: C20D1 (n=35, 8) | Emotional Functioning: C21D1 (n=30, 8) | Emotional Functioning: C22D1 (n=24, 7) | Emotional Functioning: C23D1 (n=23, 4) | Emotional Functioning: C24D1 (n=20, 3) | Emotional Functioning: C25D1 (n=18, 3) | Emotional Functioning: C26D1 (n=14, 3) | Emotional Functioning: C27D1 (n=14, 2) | Emotional Functioning: C28D1 (n=11, 2) | Emotional Functioning: C29D1 (n=8, 2) | Emotional Functioning: C30D1 (n=8, 1) | Emotional Functioning: C31D1 (n=7, 0) | Emotional Functioning: C32D1 (n=6, 0) | Emotional Functioning: C33D1 (n=6, 0) | Emotional Functioning: C34D1 (n=5, 0) | Emotional Functioning: C35D1 (n=4, 0) | Emotional Functioning: C36D1 (n=1, 0) | Emotional Functioning: C37D1 (n=1, 0) | Cognitive Functioning: Baseline (n=165, 162) | Cognitive Functioning: C2D1 (n=155, 133) | Cognitive Functioning: C3D1 (n=154, 106) | Cognitive Functioning: C4D1 (n=135, 90) | Cognitive Functioning: C5D1 (n=123, 74) | Cognitive Functioning: C6D1 (n=120, 70) | Cognitive Functioning: C7D1 (n=115, 52) | Cognitive Functioning: C8D1 (n=111, 43) | Cognitive Functioning: C9D1 (n=101, 37) | Cognitive Functioning: C10D1 (n=94, 33) | Cognitive Functioning: C11D1 (n=84, 25) | Cognitive Functioning: C12D1 (n=76, 23) | Cognitive Functioning: C13D1 (n=74, 21) | Cognitive Functioning: C14D1 (n=66, 19) | Cognitive Functioning: C15D1 (n=62, 16) | Cognitive Functioning: C16D1 (n=53, 12) | Cognitive Functioning: C17D1 (n=47, 11) | Cognitive Functioning: C18D1 (n=44, 11) | Cognitive Functioning: C19D1 (n=40, 9) | Cognitive Functioning: C20D1 (n=35, 8) | Cognitive Functioning: C21D1 (n=30, 8) | Cognitive Functioning: C22D1 (n=24, 7) | Cognitive Functioning: C23D1 (n=23, 4) | Cognitive Functioning: C24D1 (n=20, 3) | Cognitive Functioning: C25D1 (n=18, 3) | Cognitive Functioning: C26D1 (n=14, 3) | Cognitive Functioning: C27D1 (n=14, 2) | Cognitive Functioning: C28D1 (n=11, 2) | Cognitive Functioning: C29D1 (n=8, 2) | Cognitive Functioning: C30D1 (n=8, 1) | Cognitive Functioning: C31D1 (n=7, 0) | Cognitive Functioning: C32D1 (n=6, 0) | Cognitive Functioning: C33D1 (n=6, 0) | Cognitive Functioning: C34D1 (n=5, 0) | Cognitive Functioning: C35D1 (n=4, 0) | Cognitive Functioning: C36D1 (n=1, 0) | Cognitive Functioning: C37D1 (n=1, 0) | Social Functioning: Baseline (n=165, 162) | Social Functioning: C2D1 (n=155, 133) | Social Functioning: C3D1 (n=154, 106) | Social Functioning: C4D1 (n=135, 90) | Social Functioning: C5D1 (n=123, 74) | Social Functioning: C6D1 (n=120, 70) | Social Functioning: C7D1 (n=115, 52) | Social Functioning: C8D1 (n=111, 43) | Social Functioning: C9D1 (n=101, 37) | Social Functioning: C10D1 (n=94, 33) | Social Functioning: C11D1 (n=84, 25) | Social Functioning: C12D1 (n=76, 23) | Social Functioning: C13D1 (n=74, 21) | Social Functioning: C14D1 (n=66, 19) | Social Functioning: C15D1 (n=62, 16) | Social Functioning: C16D1 (n=53, 12) | Social Functioning: C17D1 (n=47, 11) | Social Functioning: C18D1 (n=44, 11) | Social Functioning: C19D1 (n=40, 9) | Social Functioning: C20D1 (n=35, 8) | Social Functioning: C21D1 (n=30, 8) | Social Functioning: C22D1 (n=24, 7) | Social Functioning: C23D1 (n=23, 4) | Social Functioning: C24D1 (n=20, 3) | Social Functioning: C25D1 (n=18, 3) | Social Functioning: C26D1 (n=14, 3) | Social Functioning: C27D1 (n=14, 2) | Social Functioning: C28D1 (n=11, 2) | Social Functioning: C29D1 (n=8, 2) | Social Functioning: C30D1 (n=8, 1) | Social Functioning: C31D1 (n=7, 0) | Social Functioning: C32D1 (n=6, 0) | Social Functioning: C33D1 (n=6, 0) | Social Functioning: C34D1 (n=5, 0) | Social Functioning: C35D1 (n=4, 0) | Social Functioning: C36D1 (n=1, 0) | Social Functioning: C37D1 (n=1, 0) | Fatigue: Baseline (n=165, 163) | Fatigue: C2D1 (n=155, 133) | Fatigue: C3D1 (n=154, 106) | Fatigue: C4D1 (n=135, 91) | Fatigue: C5D1 (n=123, 74) | Fatigue: C6D1 (n=120, 70) | Fatigue: C7D1 (n=115, 52) | Fatigue: C8D1 (n=111, 43) | Fatigue: C9D1 (n=101, 37) | Fatigue: C10D1 (n=94, 33) | Fatigue: C11D1 (n=84, 25) | Fatigue: C12D1 (n=76, 23) | Fatigue: C13D1 (n=74, 21) | Fatigue: C14D1 (n=66, 19) | Fatigue: C15D1 (n=62, 16) | Fatigue: C16D1 (n=53, 12) | Fatigue: C17D1 (n=47, 11) | Fatigue: C18D1 (n=45, 11) | Fatigue: C19D1 (n=40, 9) | Fatigue: C20D1 (n=35, 8) | Fatigue: C21D1 (n=30, 8) | Fatigue: C22D1 (n=24, 7) | Fatigue: C23D1 (n=23, 4) | Fatigue: C24D1 (n=20, 3) | Fatigue: C25D1 (n=18, 3) | Fatigue: C26D1 (n=14, 3) | Fatigue: C27D1 (n=14, 2) | Fatigue: C28D1 (n=11, 2) | Fatigue: C29D1 (n=8, 2) | Fatigue: C30D1 (n=8, 1) | Fatigue: C31D1 (n=7, 0) | Fatigue: C32D1 (n=6, 0) | Fatigue: C33D1 (n=6, 0) | Fatigue: C34D1 (n=5, 0) | Fatigue: C35D1 (n=4, 0) | Fatigue: C36D1 (n=1, 0) | Fatigue: C37D1 (n=1, 0) | Nausea and Vomiting: Baseline (n=165, 163) | Nausea and Vomiting: C2D1 (n=155, 133) | Nausea and Vomiting: C3D1 (n=154, 106) | Nausea and Vomiting: C4D1 (n=135, 91) | Nausea and Vomiting: C5D1 (n=123, 74) | Nausea and Vomiting: C6D1 (n=120, 70) | Nausea and Vomiting: C7D1 (n=115, 52) | Nausea and Vomiting: C8D1 (n=111, 43) | Nausea and Vomiting: C9D1 (n=101, 37) | Nausea and Vomiting: C10D1 (n=94, 33) | Nausea and Vomiting: C11D1 (n=84, 25) | Nausea and Vomiting: C12D1 (n=76, 23) | Nausea and Vomiting: C13D1 (n=74, 21) | Nausea and Vomiting: C14D1 (n=66, 19) | Nausea and Vomiting: C15D1 (n=62, 16) | Nausea and Vomiting: C16D1 (n=53, 12) | Nausea and Vomiting: C17D1 (n=47, 11) | Nausea and Vomiting: C18D1 (n=45, 11) | Nausea and Vomiting: C19D1 (n=40, 9) | Nausea and Vomiting: C20D1 (n=35, 8) | Nausea and Vomiting: C21D1 (n=30, 8) | Nausea and Vomiting: C22D1 (n=24, 7) | Nausea and Vomiting: C23D1 (n=23, 4) | Nausea and Vomiting: C24D1 (n=20, 3) | Nausea and Vomiting: C25D1 (n=18, 3) | Nausea and Vomiting: C26D1 (n=14, 3) | Nausea and Vomiting: C27D1 (n=14, 2) | Nausea and Vomiting: C28D1 (n=11, 2) | Nausea and Vomiting: C29D1 (n=8, 2) | Nausea and Vomiting: C30D1 (n=8, 1) | Nausea and Vomiting: C31D1 (n=7, 0) | Nausea and Vomiting: C32D1 (n=6, 0) | Nausea and Vomiting: C33D1 (n=6, 0) | Nausea and Vomiting: C34D1 (n=5, 0) | Nausea and Vomiting: C35D1 (n=4, 0) | Nausea and Vomiting: C36D1 (n=1, 0) | Nausea and Vomiting: C37D1 (n=1, 0) | Pain: Baseline (n=165, 163) | Pain: C2D1 (n=155, 133) | Pain: C3D1 (n=154, 106) | Pain: C4D1 (n=135, 91) | Pain: C5D1 (n=123, 74) | Pain: C6D1 (n=120, 70) | Pain: C7D1 (n=115, 52) | Pain: C8D1 (n=111, 43) | Pain: C9D1 (n=101, 37) | Pain: C10D1 (n=94, 33) | Pain: C11D1 (n=84, 25) | Pain: C12D1 (n=76, 23) | Pain: C13D1 (n=74, 21) | Pain: C14D1 (n=66, 19) | Pain: C15D1 (n=62, 16) | Pain: C16D1 (n=53, 12) | Pain: C17D1 (n=47, 11) | Pain: C18D1 (n=45, 11) | Pain: C19D1 (n=40, 9) | Pain: C20D1 (n=35, 8) | Pain: C21D1 (n=30, 8) | Pain: C22D1 (n=24, 7) | Pain: C23D1 (n=23, 4) | Pain: C24D1 (n=20, 3) | Pain: C25D1 (n=18, 3) | Pain: C26D1 (n=14, 3) | Pain: C27D1 (n=14, 2) | Pain: C28D1 (n=11, 2) | Pain: C29D1 (n=8, 2) | Pain: C30D1 (n=8, 1) | Pain: C31D1 (n=7, 0) | Pain: C32D1 (n=6, 0) | Pain: C33D1 (n=6, 0) | Pain: C34D1 (n=5, 0) | Pain: C35D1 (n=4, 0) | Pain: C36D1 (n=1, 0) | Pain: C37D1 (n=1, 0) | Dyspnea: Baseline (n=165, 163) | Dyspnea: C2D1 (n=155, 133) | Dyspnea: C3D1 (n=154, 106) | Dyspnea: C4D1 (n=135, 91) | Dyspnea: C5D1 (n=123, 74) | Dyspnea: C6D1 (n=120, 70) | Dyspnea: C7D1 (n=115, 52) | Dyspnea: C8D1 (n=111, 43) | Dyspnea: C9D1 (n=101, 37) | Dyspnea: C10D1 (n=94, 33) | Dyspnea: C11D1 (n=84, 25) | Dyspnea: C12D1 (n=76, 23) | Dyspnea: C13D1 (n=74, 21) | Dyspnea: C14D1 (n=66, 19) | Dyspnea: C15D1 (n=62, 16) | Dyspnea: C16D1 (n=53, 12) | Dyspnea: C17D1 (n=46, 11) | Dyspnea: C18D1 (n=45, 11) | Dyspnea: C19D1 (n=40, 9) | Dyspnea: C20D1 (n=35, 8) | Dyspnea: C21D1 (n=30, 8) | Dyspnea: C22D1 (n=24, 7) | Dyspnea: C23D1 (n=23, 4) | Dyspnea: C24D1 (n=20, 3) | Dyspnea: C25D1 (n=18, 3) | Dyspnea: C26D1 (n=14, 3) | Dyspnea: C27D1 (n=14, 2) | Dyspnea: C28D1 (n=11, 2) | Dyspnea: C29D1 (n=8, 2) | Dyspnea: C30D1 (n=8, 1) | Dyspnea: C31D1 (n=7, 0) | Dyspnea: C32D1 (n=6, 0) | Dyspnea: C33D1 (n=6, 0) | Dyspnea: C34D1 (n=5, 0) | Dyspnea: C35D1 (n=4, 0) | Dyspnea: C36D1 (n=1, 0) | Dyspnea: C37D1 (n=1, 0) | Insomnia : Baseline (n=164, 163) | Insomnia : C2D1 (n=155, 133) | Insomnia : C3D1 (n=154, 106) | Insomnia : C4D1 (n=135, 91) | Insomnia : C5D1 (n=123, 74) | Insomnia : C6D1 (n=120, 70) | Insomnia : C7D1 (n=114, 52) | Insomnia : C8D1 (n=111, 43) | Insomnia : C9D1 (n=100, 37) | Insomnia : C10D1 (n=94, 33) | Insomnia : C11D1 (n=84, 25) | Insomnia : C12D1 (n=76, 23) | Insomnia : C13D1 (n=74, 21) | Insomnia : C14D1 (n=66, 19) | Insomnia : C15D1 (n=62, 16) | Insomnia : C16D1 (n=53, 11) | Insomnia : C17D1 (n=47, 11) | Insomnia : C18D1 (n=45, 11) | Insomnia : C19D1 (n=40, 9) | Insomnia : C20D1 (n=35, 8) | Insomnia : C21D1 (n=30, 8) | Insomnia : C22D1 (n=24, 7) | Insomnia : C23D1 (n=23, 4) | Insomnia : C24D1 (n=20, 3) | Insomnia : C25D1 (n=18, 3) | Insomnia : C26D1 (n=14, 3) | Insomnia : C27D1 (n=14, 2) | Insomnia : C28D1 (n=11, 2) | Insomnia : C29D1 (n=8, 2) | Insomnia : C30D1 (n=8, 1) | Insomnia : C31D1 (n=7, 0) | Insomnia : C32D1 (n=6, 0) | Insomnia : C33D1 (n=6, 0) | Insomnia : C34D1 (n=5, 0) | Insomnia : C35D1 (n=4, 0) | Insomnia : C36D1 (n=1, 0) | Insomnia : C37D1 (n=1, 0) | Appetite loss : Baseline(n=165, 163) | Appetite loss : C2/D1(n=155, 133) | Appetite loss : C3/D1(n=154, 106) | Appetite loss : C4/D1(n=135, 91) | Appetite loss : C5/D1(n=123, 74) | Appetite loss : C6/D1(n=120, 70) | Appetite loss : C7/D1(n=115, 52) | Appetite loss : C8/D1(n=111, 43) | Appetite loss : C9/D1(n=101, 37) | Appetite loss : C10/D1(n=94, 33) | Appetite loss : C11/D1(n=84, 25) | Appetite loss : C12/D1(n=76, 23) | Appetite loss : C13/D1(n=74, 21) | Appetite loss : C15/D1(n=62, 16) | Appetite loss : C16/D1(n=53, 12) | Appetite loss : C17/D1(n=47, 11) | Appetite loss : C18/D1(n=45, 11) | Appetite loss : C19/D1(n=40, 9) | Appetite loss : C20/D1(n=35, 8) | Appetite loss : C21/D1(n=30, 8) | Appetite loss : C22/D1(n=24, 7) | Appetite loss : C23/D1(n=23, 4) | Appetite loss : C24/D1(n=20, 3) | Appetite loss : C25/D1(n=18, 3) | Appetite loss : C26/D1(n=14, 3) | Appetite loss : C27/D1(n=14, 2) | Appetite loss : C28/D1(n=11, 2) | Appetite loss : C29/D1(n=8, 2) | Appetite loss : C30/D1(n=8, 1) | Appetite loss : C31/D1(n=7, 0) | Constipation: Baseline (n=164, 162) | Constipation: C2D1 (n=155, 133) | Constipation: C3D1 (n=154, 106) | Constipation: C4D1 (n=134, 90) | Constipation: C5D1 (n=123, 74) | Constipation: C6D1 (n=120, 70) | Constipation: C7D1 (n=115, 52) | Constipation: C8D1 (n=111, 43) | Constipation: C9D1 (n=101, 37) | Constipation: C10D1 (n=94, 33) | Constipation: C11D1 (n=84, 25) | Constipation: C12D1 (n=76, 23) | Constipation: C13D1 (n=74, 21) | Constipation: C14D1 (n=66, 19) | Constipation: C15D1 (n=62, 16) | Constipation: C16D1 (n=53, 12) | Constipation: C17D1 (n=47, 11) | Constipation: C18D1 (n=44, 11) | Constipation: C19D1 (n=40, 9) | Constipation: C20D1 (n=35, 8) | Constipation: C21D1 (n=30, 8) | Constipation: C22D1 (n=24, 7) | Constipation: C23D1 (n=23, 4) | Constipation: C24D1 (n=20, 3) | Constipation: C25D1 (n=18, 3) | Constipation: C26D1 (n=14, 3) | Constipation: C27D1 (n=14, 2) | Constipation: C28D1 (n=11, 2) | Constipation: C29D1 (n=8, 2) | Constipation: C30D1 (n=8, 1) | Constipation: C31D1 (n=7, 0) | Constipation: C32D1 (n=6, 0) | Constipation: C33D1 (n=6, 0) | Constipation: C34D1 (n=5, 0) | Constipation: C35D1 (n=4, 0) | Constipation: C36D1 (n=1, 0) | Constipation: C37D1 (n=1, 0) | Constipation: EOT (n=49, 90) | Diarrhea: Baseline (n=165, 162) | Diarrhea: C2D1 (n=155, 132) | Diarrhea: C3D1 (n=153, 106) | Diarrhea: C4D1 (n=134, 90) | Diarrhea: C5D1 (n=123, 74) | Diarrhea: C6D1 (n=120, 70) | Diarrhea: C7D1 (n=115, 52) | Diarrhea: C8D1 (n=111, 43) | Diarrhea: C9D1 (n=101, 37) | Diarrhea: C10D1 (n=94, 33) | Diarrhea: C11D1 (n=84, 25) | Diarrhea: C12D1 (n=76, 23) | Diarrhea: C13D1 (n=74, 21) | Diarrhea: C14D1 (n=66, 19) | Diarrhea: C15D1 (n=62, 16) | Diarrhea: C16D1 (n=52, 12) | Diarrhea: C17D1 (n=47, 11) | Diarrhea: C18D1 (n=44, 11) | Diarrhea: C19D1 (n=40, 9) | Diarrhea: C20D1 (n=35, 8) | Diarrhea: C21D1 (n=30, 8) | Diarrhea: C22D1 (n=24, 7) | Diarrhea: C23D1 (n=23, 4) | Diarrhea: C24D1 (n=20, 3) | Diarrhea: C25D1 (n=18, 3) | Diarrhea: C26D1 (n=14, 3) | Diarrhea: C27D1 (n=14, 2) | Diarrhea: C28D1 (n=11, 2) | Diarrhea: C29D1 (n=8, 2) | Diarrhea: C30D1 (n=8, 1) | Diarrhea: C31D1 (n=7, 0) | Diarrhea: C32D1 (n=6, 0) | Diarrhea: C33D1 (n=6, 0) | Diarrhea: C34D1 (n=5, 0) | Diarrhea: C35D1 (n=4, 0) | Diarrhea: C36D1 (n=1, 0) | Diarrhea: C37D1 (n=1, 0) | Diarrhea: EOT (n=49, 90) | Financial Difficulties: Baseline (n=165, 161) | Financial Difficulties: C2D1 (n=155, 133) | Financial Difficulties: C3D1 (n=154, 105) | Financial Difficulties: C4D1 (n=135, 90) | Financial Difficulties: C5D1 (n=123, 74) | Financial Difficulties: C6D1 (n=120, 70) | Financial Difficulties: C7D1 (n=115, 52) | Financial Difficulties: C8D1 (n=111, 43) | Financial Difficulties: C9D1 (n=101, 36) | Financial Difficulties: C10D1 (n=94, 33) | Financial Difficulties: C11D1 (n=84, 25) | Financial Difficulties: C12D1 (n=76, 23) | Financial Difficulties: C13D1 (n=74, 21) | Financial Difficulties: C14D1 (n=66, 19) | Financial Difficulties: C15D1 (n=62, 16) | Financial Difficulties: C16D1 (n=53, 12) | Financial Difficulties: C17D1 (n=47, 11) | Financial Difficulties: C18D1 (n=44, 11) | Financial Difficulties: C19D1 (n=40, 9) | Financial Difficulties: C20D1 (n=35, 8) | Financial Difficulties: C21D1 (n=30, 8) | Financial Difficulties: C22D1 (n=24, 7) | Financial Difficulties: C23D1 (n=23, 4) | Financial Difficulties: C24D1 (n=20, 3) | Financial Difficulties: C25D1 (n=18, 3) | Financial Difficulties: C26D1 (n=14, 3) | Financial Difficulties: C27D1 (n=14, 2) | Financial Difficulties: C28D1 (n=11, 2) | Financial Difficulties: C29D1 (n=8, 2) | Financial Difficulties: C30D1 (n=8, 1) | Financial Difficulties: C31D1 (n=7, 0) | Financial Difficulties: C32D1 (n=6, 0) | Financial Difficulties: C33D1 (n=6, 0) | Financial Difficulties: C34D1 (n=5, 0) | Financial Difficulties: C35D1 (n=4, 0) | Financial Difficulties: C36D1 (n=1, 0) | Financial Difficulties: C37D1 (n=1, 0) | Financial Difficulties: EOT (n=49, 90) | Appetite loss: C32D1 (n=6, 0) | Appetite loss: C33D1 (n=6, 0) | Appetite loss: C34D1 (n=5, 0) | Appetite loss: C35D1 (n=4, 0) | Appetite loss: C36D1 (n=1, 0) | Appetite loss: C37D1 (n=1, 0) | Appetite loss: EOT (n=49, 90) | Global Qol: EOT (n=49, 90) | Physical Functioning: EOT (n=49, 90) | Role Functioning: EOT (n=49, 90) | Emotional Functioning: EOT (n=49, 90) | Cognitive Functioning: EOT (n=49, 90) | Social Function: EOT (n=49, 90) | Fatigue: EOT (n=49, 90) | Nausea and Vomiting: EOT (n=49, 90) | Pain: EOT (n=49, 90) | Dyspnea: EOT (n=49, 90) | Insomnia: EOT (n=49, 90) |
|---|
| Chemotherapy | 58.1 | 58.1 | 59.4 | 61.1 | 64.1 | 67.5 | 66.5 | 66.9 | 66.4 | 67.4 | 71.0 | 65.6 | 66.7 | 65.8 | 66.1 | 63.2 | 69.7 | 70.5 | 72.2 | 60.4 | 63.5 | 64.3 | 50.0 | 55.6 | 61.1 | 55.6 | 41.7 | 54.2 | 41.7 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 75.8 | 73.5 | 75.5 | 76.6 | 78.6 | 80.7 | 80.3 | 81.6 | 82.3 | 81.8 | 83.2 | 79.7 | 78.4 | 80.0 | 82.9 | 81.1 | 81.8 | 82.4 | 81.5 | 79.2 | 77.5 | 78.1 | 60.0 | 64.4 | 60.0 | 62.2 | 50.0 | 60.0 | 46.7 | 26.7 | NA | NA | NA | NA | NA | NA | NA | 66.6 | 64.7 | 65.3 | 67.2 | 69.6 | 69.5 | 72.1 | 75.2 | 76.6 | 75.3 | 75.3 | 72.5 | 68.3 | 68.4 | 77.1 | 69.4 | 71.2 | 71.2 | 74.1 | 70.8 | 66.7 | 67.9 | 37.5 | 44.4 | 44.4 | 33.3 | 25.0 | 25.0 | 25.0 | 0.0 | NA | NA | NA | NA | NA | NA | NA | 73.7 | 77.7 | 77.9 | 80.5 | 79.8 | 81.2 | 81.9 | 81.6 | 82.4 | 81.8 | 85.0 | 84.8 | 80.6 | 81.6 | 82.3 | 77.8 | 79.5 | 75.8 | 81.5 | 82.3 | 80.2 | 78.6 | 70.8 | 66.7 | 72.2 | 72.2 | 58.3 | 58.3 | 54.2 | 58.3 | NA | NA | NA | NA | NA | NA | NA | 83.6 | 84.5 | 83.8 | 82.6 | 82.7 | 83.8 | 85.3 | 82.2 | 84.7 | 80.8 | 85.3 | 80.4 | 79.4 | 81.6 | 84.4 | 72.2 | 75.8 | 75.8 | 70.4 | 72.9 | 72.9 | 69.0 | 58.3 | 61.1 | 55.6 | 61.1 | 41.7 | 41.7 | 33.3 | 16.7 | NA | NA | NA | NA | NA | NA | NA | 67.1 | 69.5 | 72.5 | 71.7 | 74.5 | 76.4 | 77.9 | 77.5 | 80.2 | 76.3 | 78.7 | 71.0 | 71.4 | 69.3 | 74.0 | 65.3 | 69.7 | 65.2 | 64.8 | 70.8 | 64.6 | 65.5 | 41.7 | 61.1 | 50.0 | 50.0 | 33.3 | 33.3 | 33.3 | 0.0 | NA | NA | NA | NA | NA | NA | NA | 36.1 | 39.5 | 39.4 | 34.1 | 31.5 | 31.0 | 27.6 | 26.6 | 28.5 | 28.6 | 22.2 | 26.1 | 27.5 | 28.1 | 24.3 | 24.1 | 23.2 | 27.3 | 24.7 | 27.8 | 25.7 | 27.0 | 47.2 | 40.7 | 44.4 | 44.4 | 55.6 | 38.9 | 50.0 | 55.6 | NA | NA | NA | NA | NA | NA | NA | 11.7 | 12.7 | 9.9 | 8.1 | 9.0 | 6.9 | 7.7 | 8.9 | 9.5 | 8.1 | 8.0 | 7.2 | 7.1 | 7.0 | 6.2 | 6.9 | 10.6 | 3.0 | 9.3 | 10.4 | 8.3 | 14.3 | 45.8 | 33.3 | 27.8 | 33.3 | 33.3 | 25.0 | 25.0 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 28.0 | 25.7 | 23.3 | 19.0 | 20.5 | 19.5 | 21.5 | 17.4 | 23.0 | 24.2 | 22.0 | 25.4 | 27.8 | 23.7 | 22.9 | 31.9 | 24.2 | 24.2 | 24.1 | 22.9 | 29.2 | 33.3 | 33.3 | 27.8 | 38.9 | 38.9 | 58.3 | 50.0 | 41.7 | 83.3 | NA | NA | NA | NA | NA | NA | NA | 32.5 | 33.6 | 33.3 | 29.3 | 29.3 | 26.2 | 28.2 | 22.5 | 23.4 | 24.2 | 25.3 | 30.4 | 23.8 | 29.8 | 20.8 | 19.4 | 24.2 | 24.2 | 25.9 | 33.3 | 33.3 | 28.6 | 41.7 | 44.4 | 33.3 | 33.3 | 50.0 | 50.0 | 50.0 | 66.7 | NA | NA | NA | NA | NA | NA | NA | 27.8 | 27.1 | 23.6 | 23.8 | 25.7 | 23.3 | 21.8 | 21.7 | 22.5 | 24.2 | 22.7 | 23.2 | 25.4 | 24.6 | 29.2 | 21.2 | 15.2 | 21.2 | 22.2 | 20.8 | 29.2 | 31.0 | 50.0 | 22.2 | 44.4 | 22.2 | 50.0 | 50.0 | 33.0 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 23.3 | 24.3 | 21.7 | 19.4 | 19.4 | 12.9 | 12.8 | 10.9 | 14.4 | 14.1 | 14.7 | 14.5 | 17.5 | 12.5 | 16.7 | 15.2 | 12.1 | 18.5 | 20.8 | 25.0 | 14.3 | 50.0 | 33.3 | 44.4 | 33.3 | 33.3 | 33.3 | 33.3 | 100.0 | NA | 16.9 | 14.0 | 16.0 | 14.8 | 20.3 | 15.7 | 19.9 | 16.3 | 16.2 | 19.2 | 21.3 | 21.7 | 22.2 | 24.6 | 18.7 | 22.2 | 24.2 | 15.2 | 22.2 | 20.8 | 16.7 | 19.0 | 25.0 | 22.2 | 33.3 | 44.4 | 50.0 | 50.0 | 50.0 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 18.1 | 7.8 | 11.1 | 7.9 | 8.5 | 5.9 | 7.1 | 9.6 | 9.3 | 7.2 | 7.1 | 8.0 | 8.7 | 12.7 | 8.8 | 4.2 | 5.6 | 12.1 | 12.1 | 7.4 | 4.2 | 8.3 | 11.9 | 25.0 | 11.1 | 22.2 | 11.1 | 16.7 | 16.7 | 16.7 | 0.0 | NA | NA | NA | NA | NA | NA | NA | 10.0 | 27.3 | 22.3 | 20.3 | 21.9 | 19.4 | 18.6 | 18.6 | 15.5 | 16.7 | 15.2 | 17.3 | 18.8 | 17.5 | 17.5 | 16.7 | 30.6 | 33.3 | 15.2 | 25.9 | 25.0 | 29.2 | 28.6 | 33.3 | 33.3 | 44.4 | 44.4 | 66.7 | 66.7 | 66.7 | 100.0 | NA | NA | NA | NA | NA | NA | NA | 24.1 | NA | NA | NA | NA | NA | NA | 28.1 | 46.4 | 66.2 | 54.1 | 74.5 | 80.0 | 59.4 | 46.9 | 15.7 | 33.7 | 40.0 | 30.4 |
,| Crizotinib | 57.2 | 64.5 | 65.2 | 68.4 | 68.5 | 68.3 | 69.5 | 68.7 | 68.7 | 67.0 | 69.5 | 67.9 | 66.8 | 71.5 | 69.0 | 69.7 | 67.6 | 65.7 | 69.2 | 64.3 | 65.0 | 70.8 | 67.0 | 67.1 | 67.1 | 60.7 | 58.9 | 66.7 | 59.4 | 64.6 | 64.3 | 59.7 | 66.7 | 68.3 | 60.4 | 66.7 | 66.7 | 76.3 | 79.2 | 82.3 | 83.8 | 84.5 | 86.2 | 86.7 | 86.5 | 87.7 | 87.9 | 87.2 | 88.1 | 89.3 | 89.0 | 87.8 | 89.3 | 86.6 | 88.4 | 88.3 | 87.6 | 88.4 | 90.6 | 88.0 | 85.0 | 87.4 | 80.5 | 78.6 | 81.8 | 85.0 | 82.5 | 83.8 | 88.9 | 90.0 | 85.3 | 91.7 | 86.7 | 86.7 | 69.3 | 73.8 | 74.4 | 77.9 | 78.2 | 80.0 | 81.7 | 80.4 | 80.9 | 81.6 | 81.3 | 81.6 | 80.2 | 83.8 | 80.6 | 84.0 | 77.7 | 80.0 | 82.1 | 81.9 | 80.0 | 84.7 | 76.8 | 80.8 | 87.0 | 75.0 | 69.0 | 77.3 | 77.1 | 77.1 | 71.4 | 86.1 | 88.9 | 96.7 | 91.7 | 100.0 | 100.0 | 74.5 | 83.1 | 83.3 | 84.1 | 83.0 | 85.3 | 86.4 | 83.9 | 84.4 | 87.2 | 86.1 | 85.3 | 84.9 | 84.5 | 86.3 | 85.8 | 85.6 | 86.4 | 87.3 | 83.8 | 84.5 | 83.7 | 84.1 | 87.9 | 81.5 | 73.2 | 70.8 | 81.1 | 86.5 | 84.4 | 76.2 | 87.5 | 90.3 | 91.7 | 83.3 | 58.3 | 58.3 | 85.6 | 85.5 | 87.0 | 88.1 | 88.9 | 87.5 | 86.7 | 87.8 | 88.3 | 89.2 | 87.9 | 89.5 | 88.5 | 88.9 | 87.6 | 87.4 | 85.1 | 88.3 | 87.5 | 85.7 | 85.6 | 86.1 | 85.5 | 85.8 | 86.1 | 81.0 | 76.2 | 78.8 | 87.5 | 83.3 | 81.0 | 83.3 | 86.1 | 90.0 | 95.8 | 100.0 | 83.3 | 68.0 | 75.9 | 78.5 | 79.4 | 79.4 | 81.8 | 82.3 | 82.0 | 80.4 | 81.9 | 81.9 | 82.0 | 81.8 | 81.3 | 81.5 | 82.7 | 81.9 | 82.6 | 84.6 | 82.9 | 82.8 | 82.6 | 84.4 | 84.2 | 89.8 | 78.6 | 85.7 | 83.3 | 83.3 | 85.4 | 73.8 | 83.3 | 94.4 | 96.7 | 91.7 | 66.7 | 66.7 | 38.3 | 31.4 | 30.8 | 27.1 | 24.7 | 24.6 | 23.9 | 23.2 | 22.9 | 21.4 | 22.1 | 21.9 | 23.3 | 21.7 | 20.8 | 22.2 | 23.4 | 21.5 | 20.8 | 24.4 | 23.9 | 23.6 | 25.1 | 24.4 | 24.7 | 30.2 | 35.7 | 28.3 | 30.6 | 26.4 | 28.6 | 25.9 | 18.5 | 15.6 | 27.8 | 33.3 | 11.1 | 8.4 | 15.2 | 13.9 | 9.9 | 9.2 | 10.1 | 7.1 | 8.8 | 6.9 | 8.5 | 8.3 | 6.4 | 8.6 | 5.8 | 5.9 | 5.3 | 7.8 | 7.0 | 8.8 | 7.4 | 7.8 | 2.8 | 5.4 | 7.5 | 3.7 | 10.7 | 11.9 | 3.0 | 10.4 | 6.3 | 14.3 | 11.1 | 11.1 | 13.3 | 12.5 | 0.0 | 0.0 | 23.9 | 13.9 | 13.7 | 13.0 | 11.5 | 10.6 | 9.6 | 11.3 | 11.8 | 8.7 | 10.5 | 8.6 | 10.1 | 8.1 | 9.4 | 9.4 | 10.6 | 11.1 | 11.3 | 11.9 | 11.7 | 6.9 | 9.1 | 4.2 | 4.6 | 17.9 | 13.1 | 4.5 | 2.1 | 4.2 | 4.8 | 5.6 | 2.8 | 3.3 | 8.3 | 0.0 | 0.0 | 31.1 | 21.5 | 21.6 | 17.3 | 16.0 | 15.8 | 17.4 | 15.8 | 13.9 | 17.7 | 17.5 | 14.5 | 14.0 | 15.2 | 15.6 | 13.8 | 14.5 | 14.1 | 14.2 | 10.5 | 13.3 | 13.9 | 9.4 | 18.3 | 11.1 | 14.3 | 11.9 | 12.1 | 4.2 | 8.3 | 9.5 | 16.7 | 11.1 | 13.3 | 16.7 | 0.0 | 0.0 | 22.6 | 15.3 | 16.2 | 13.3 | 13.6 | 14.2 | 9.4 | 12.5 | 12.3 | 13.5 | 13.9 | 13.6 | 10.8 | 11.1 | 11.3 | 13.8 | 13.5 | 12.6 | 13.3 | 15.2 | 12.2 | 12.5 | 17.4 | 11.7 | 20.4 | 21.4 | 16.7 | 9.1 | 8.3 | 12.5 | 0.0 | 5.6 | 5.6 | 13.3 | 16.7 | 0.0 | 0.0 | 24.4 | 21.1 | 18.4 | 14.6 | 12.7 | 13.6 | 10.4 | 12.8 | 12.2 | 12.4 | 13.5 | 11.0 | 9.5 | 8.6 | 8.8 | 8.5 | 11.1 | 8.3 | 7.6 | 11.1 | 6.9 | 9.4 | 5.0 | 1.9 | 11.9 | 7.1 | 15.2 | 12.5 | 8.3 | 14.3 | 14.8 | 28.6 | 27.1 | 22.9 | 21.4 | 21.7 | 21.7 | 18.6 | 18.8 | 16.0 | 21.0 | 19.7 | 21.2 | 21.7 | 22.6 | 19.5 | 22.0 | 22.7 | 25.0 | 22.9 | 24.4 | 18.1 | 11.6 | 21.7 | 22.2 | 26.2 | 35.7 | 21.2 | 29.2 | 29.2 | 33.3 | 33.3 | 38.9 | 40.0 | 33.3 | 0.0 | 0.0 | 28.6 | 9.7 | 18.1 | 21.6 | 23.1 | 24.4 | 22.2 | 20.6 | 18.6 | 17.3 | 17.7 | 21.0 | 17.5 | 17.6 | 17.7 | 16.1 | 16.0 | 19.9 | 22.7 | 21.7 | 21.0 | 22.2 | 23.6 | 15.9 | 21.7 | 20.4 | 19.0 | 23.8 | 15.2 | 20.8 | 12.5 | 14.3 | 11.1 | 11.1 | 6.7 | 16.7 | 33.3 | 33.3 | 18.4 | 28.5 | 21.9 | 19.0 | 17.5 | 16.8 | 15.6 | 14.8 | 16.8 | 17.8 | 16.3 | 17.5 | 17.1 | 16.2 | 14.1 | 14.0 | 15.7 | 17.7 | 18.9 | 17.5 | 16.2 | 13.3 | 18.1 | 17.4 | 20.0 | 11.1 | 14.3 | 14.3 | 15.2 | 8.3 | 4.2 | 9.5 | 22.2 | 16.7 | 13.3 | 8.3 | 33.3 | 66.7 | 17.0 | 11.1 | 11.1 | 13.3 | 16.7 | 0.0 | 0.0 | 21.8 | 56.1 | 80.7 | 71.8 | 75.2 | 83.7 | 78.2 | 32.0 | 16.3 | 23.8 | 23.8 | 18.4 |
Time to Deterioration (TTD) in Participant Reported Pain, Dyspnea, and Cough
TTD in pain (pain in chest from European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer [EORTC QLQ-LC13]), dyspnea (from EORTC QLQ-LC13), or cough (from EORTC QLQ-LC13) symptoms was defined as the time from randomization to the earliest time the participant's score showed a 10 point or higher increase from baseline in any of the three symptoms from the instrument. The transformed score of pain, dyspnea, and cough symptom scales of EORTC QLQ-LC13 range from 0 to 100, greater scores = higher symptom severity. (NCT00932893)
Timeframe: Baseline up to end of treatment (up to 112 weeks)
| Intervention | months (Median) |
|---|
| Crizotinib | 4.5 |
| Chemotherapy | 1.4 |
Duration of Response (DR)
Time in weeks from the first documentation of objective tumor response 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 7.02. DR was calculated for the subgroup of participants with a confirmed objective tumor response. (NCT00932893)
Timeframe: Randomization until PD or initiation of antitumor therapy in the absence of PD or death, assessed every 6 weeks (up to 112 weeks)
| Intervention | weeks (Median) |
|---|
| Crizotinib | 32.1 |
| Chemotherapy | 24.4 |
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Supplement Module for Lung Cancer (EORTC QLQ-LC13)
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 dyspnea 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: 1 'Not at All' to 4 'Very Much'. Scores averaged, transformed to 0-100 scale; higher symptom score = greater degree of symptoms. (NCT00932893)
Timeframe: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Dyspnea: Baseline (n=164, 162) | Dyspnea: C2D1 (n=155, 132) | Dyspnea: C3D1 (n=153, 106) | Dyspnea: C4D1 (n=135, 91) | Dyspnea: C5D1 (n=123, 74) | Dyspnea: C6D1 (n=119, 70) | Dyspnea: C7D1 (n=115, 52) | Dyspnea: C8D1 (n=111, 43) | Dyspnea: C9D1 (n=101, 37) | Dyspnea: C10D1 (n=94, 33) | Dyspnea: C11D1 (n=84, 25) | Dyspnea: C12D1 (n=76, 23) | Dyspnea: C13D1 (n=74, 21) | Dyspnea: C14D1 (n=66, 19) | Dyspnea: C15D1 (n=62, 16) | Dyspnea: C16D1 (n=53, 12) | Dyspnea: C17D1 (n=46, 11) | Dyspnea: C18D1 (n=45, 11) | Dyspnea: C19D1 (n=40, 9) | Dyspnea: C20D1 (n=35, 8) | Dyspnea: C21D1 (n=30, 8) | Dyspnea: C22D1 (n=24, 7) | Dyspnea: C23D1 (n=23, 4) | Dyspnea: C24D1 (n=20, 3) | Dyspnea: C25D1 (n=18, 3) | Dyspnea: C26D1 (n=14, 3) | Dyspnea: C27D1 (n=14, 2) | Dyspnea: C28D1 (n=11, 2) | Dyspnea: C29D1 (n=8, 2) | Dyspnea: C30D1 (n=8, 1) | Dyspnea: C31D1 (n=7, 0) | Dyspnea: C32D1 (n=6, 0) | Dyspnea: C33D1 (n=6, 0) | Dyspnea: C34D1 (n=5, 0) | Dyspnea: C35D1 (n=4, 0) | Dyspnea: C36D1 (n=1, 0) | Dyspnea: C37D1 (n=1, 0) | Dyspnea: EOT (n=49, 90) | Coughing: Baseline (n=164, 162) | Coughing: C2D1 (n=155, 132) | Coughing: C3D1 (n=153, 106) | Coughing: C4D1 (n=135, 91) | Coughing: C5D1 (n=123, 74) | Coughing: C6D1 (n=119, 70) | Coughing: C7D1 (n=115, 52) | Coughing: C8D1 (n=111, 43) | Coughing: C9D1 (n=101, 37) | Coughing: C10D1 (n=94, 33) | Coughing: C11D1 (n=83, 25) | Coughing: C12D1 (n=76, 23) | Coughing: C13D1 (n=74, 21) | Coughing: C14D1 (n=66, 19) | Coughing: C15D1 (n=62, 16) | Coughing: C16D1 (n=53, 12) | Coughing: C17D1 (n=47, 11) | Coughing: C18D1 (n=45, 11) | Coughing: C19D1 (n=40, 9) | Coughing: C20D1 (n=35, 8) | Coughing: C21D1 (n=30, 8) | Coughing: C22D1 (n=24, 7) | Coughing: C23D1 (n=23, 4) | Coughing: C24D1 (n=20, 3) | Coughing: C25D1 (n=18, 3) | Coughing: C26D1 (n=14, 3) | Coughing: C27D1 (n=14, 2) | Coughing: C28D1 (n=11, 2) | Coughing: C29D1 (n=8, 2) | Coughing: C30D1 (n=8, 1) | Coughing: C31D1 (n=7, 0) | Coughing: C32D1 (n=6, 0) | Coughing: C33D1 (n=6, 0) | Coughing: C34D1 (n=5, 0) | Coughing: C35D1 (n=4, 0) | Coughing: C36D1 (n=1, 0) | Coughing: C37D1 (n=1, 0) | Coughing: EOT (n=49, 90) | Hemoptysis: Baseline (n=164, 162) | Hemoptysis: C2D1 (n=155, 132) | Hemoptysis: C3D1 (n=153, 106) | Hemoptysis: C4D1 (n=135, 91) | Hemoptysis: C5D1 (n=123, 74) | Hemoptysis: C6D1 (n=119, 70) | Hemoptysis: C7D1 (n=115, 52) | Hemoptysis: C8D1 (n=111, 43) | Hemoptysis: C9D1 (n=101, 37) | Hemoptysis: C10D1 (n=94, 33) | Hemoptysis: C11D1 (n=83, 25) | Hemoptysis: C12D1 (n=76, 23) | Hemoptysis: C13D1 (n=74, 21) | Hemoptysis: C14D1 (n=66, 19) | Hemoptysis: C15D1 (n=62, 16) | Hemoptysis: C16D1 (n=53, 12) | Hemoptysis: C17D1 (n=47, 11) | Hemoptysis: C18D1 (n=45, 11) | Hemoptysis: C19D1 (n=40, 9) | Hemoptysis: C20D1 (n=35, 8) | Hemoptysis: C21D1 (n=30, 8) | Hemoptysis: C22D1 (n=24, 7) | Hemoptysis: C23D1 (n=23, 4) | Hemoptysis: C24D1 (n=20, 3) | Hemoptysis: C25D1 (n=18, 3) | Hemoptysis: C26D1 (n=14, 3) | Hemoptysis: C27D1 (n=14, 2) | Hemoptysis: C28D1 (n=11, 2) | Hemoptysis: C29D1 (n=8, 2) | Hemoptysis: C30D1 (n=8, 1) | Hemoptysis: C31D1 (n=7, 0) | Hemoptysis: C32D1 (n=6, 0) | Hemoptysis: C33D1 (n=6, 0) | Hemoptysis: C34D1 (n=5, 0) | Hemoptysis: C35D1 (n=4, 0) | Hemoptysis: C36D1 (n=1, 0) | Hemoptysis: C37D1 (n=1, 0) | Hemoptysis: EOT (n=49, 90) | Sore Mouth: Baseline (n=164, 162) | Sore Mouth: C2D1 (n=155, 132) | Sore Mouth: C3D1 (n=153, 106) | Sore Mouth: C4D1 (n=135, 91) | Sore Mouth: C5D1 (n=123, 73) | Sore Mouth: C6D1 (n=119, 70) | Sore Mouth: C7D1 (n=115, 52) | Sore Mouth: C8D1 (n=111, 43) | Sore Mouth: C9D1 (n=101, 37) | Sore Mouth: C10D1 (n=94, 33) | Sore Mouth: C11D1 (n=84, 25) | Sore Mouth: C12D1 (n=76, 23) | Sore Mouth: C13D1 (n=74, 21) | Sore Mouth: C14D1 (n=66, 19) | Sore Mouth: C15D1 (n=62, 16) | Sore Mouth: C16D1 (n=53, 12) | Sore Mouth: C17D1 (n=47, 11) | Sore Mouth: C18D1 (n=45, 11) | Sore Mouth: C19D1 (n=40, 9) | Sore Mouth: C20D1 (n=35, 8) | Sore Mouth: C21D1 (n=30, 8) | Sore Mouth: C22D1 (n=24, 7) | Sore Mouth: C23D1 (n=23, 4) | Sore Mouth: C24D1 (n=20, 3) | Sore Mouth: C25D1 (n=18, 3) | Sore Mouth: C26D1 (n=14, 3) | Sore Mouth: C27D1 (n=14, 2) | Sore Mouth: C28D1 (n=11, 2) | Sore Mouth: C29D1 (n=8, 2) | Sore Mouth: C30D1 (n=8, 1) | Sore Mouth: C31D1 (n=7, 0) | Sore Mouth: C32D1 (n=6, 0) | Sore Mouth: C33D1 (n=6, 0) | Sore Mouth: C34D1 (n=5, 0) | Sore Mouth: C35D1 (n=4, 0) | Sore Mouth: C36D1 (n=1, 0) | Sore Mouth: C37D1 (n=1, 0) | Sore Mouth: EOT (n=49, 90) | Dysphagia: Baseline (n=164, 162) | Dysphagia: C2D1 (n=155, 132) | Dysphagia: C3D1 (n=153, 106) | Dysphagia: C4D1 (n=135, 91) | Dysphagia: C5D1 (n=123, 74) | Dysphagia: C6D1 (n=119, 70) | Dysphagia: C7D1 (n=115, 52) | Dysphagia: C8D1 (n=111, 43) | Dysphagia: C9D1 (n=101, 37) | Dysphagia: C10D1 (n=94, 33) | Dysphagia: C11D1 (n=84, 25) | Dysphagia: C12D1 (n=76, 23) | Dysphagia: C13D1 (n=74, 21) | Dysphagia: C14D1 (n=66, 19) | Dysphagia: C15D1 (n=62, 16) | Dysphagia: C16D1 (n=53, 12) | Dysphagia: C17D1 (n=47, 11) | Dysphagia: C18D1 (n=45, 11) | Dysphagia: C19D1 (n=40, 9) | Dysphagia: C20D1 (n=35, 8) | Dysphagia: C21D1 (n=30, 8) | Dysphagia: C22D1 (n=24, 7) | Dysphagia: C23D1 (n=23, 4) | Dysphagia: C24D1 (n=20, 3) | Dysphagia: C25D1 (n=18, 3) | Dysphagia: C26D1 (n=14, 3) | Dysphagia: C27D1 (n=14, 2) | Dysphagia: C28D1 (n=11, 2) | Dysphagia: C29D1 (n=8, 2) | Dysphagia: C30D1 (n=8, 1) | Dysphagia: C31D1 (n=7, 0) | Dysphagia: C32D1 (n=6, 0) | Dysphagia: C33D1 (n=6, 0) | Dysphagia: C34D1 (n=5, 0) | Dysphagia: C35D1 (n=4, 0) | Dysphagia: C36D1 (n=1, 0) | Dysphagia: C37D1 (n=1, 0) | Dysphagia: EOT (n=49, 90) | Peripheral Neuropathy: Baseline (n=164, 162) | Peripheral Neuropathy: C2D1 (n=155, 132) | Peripheral Neuropathy: C3D1 (n=153, 106) | Peripheral Neuropathy: C4D1 (n=134, 91) | Peripheral Neuropathy: C5D1 (n=123, 74) | Peripheral Neuropathy: C6D1 (n=119, 70) | Peripheral Neuropathy: C7D1 (n=115, 52) | Peripheral Neuropathy: C8D1 (n=111, 43) | Peripheral Neuropathy: C9D1 (n=101, 37) | Peripheral Neuropathy: C10D1 (n=94, 33) | Peripheral Neuropathy: C11D1 (n=84, 25) | Peripheral Neuropathy: C12D1 (n=76, 23) | Peripheral Neuropathy: C13D1 (n=74, 21) | Peripheral Neuropathy: C14D1 (n=66, 19) | Peripheral Neuropathy: C15D1 (n=62, 16) | Peripheral Neuropathy: C16D1 (n=52, 12) | Peripheral Neuropathy: C17D1 (n=47, 11) | Peripheral Neuropathy: C18D1 (n=45, 11) | Peripheral Neuropathy: C19D1 (n=40, 9) | Peripheral Neuropathy: C20D1 (n=35, 8) | Peripheral Neuropathy: C21D1 (n=30, 8) | Peripheral Neuropathy: C22D1 (n=24, 7) | Peripheral Neuropathy: C23D1 (n=23, 4) | Peripheral Neuropathy: C24D1 (n=20, 3) | Peripheral Neuropathy: C25D1 (n=18, 3) | Peripheral Neuropathy: C26D1 (n=14, 3) | Peripheral Neuropathy: C27D1 (n=14, 2) | Peripheral Neuropathy: C28D1 (n=11, 2) | Peripheral Neuropathy: C29D1 (n=8, 2) | Peripheral Neuropathy: C30D1 (n=8, 1) | Peripheral Neuropathy: C31D1 (n=7, 0) | Peripheral Neuropathy: C32D1 (n=6, 0) | Peripheral Neuropathy: C33D1 (n=6, 0) | Peripheral Neuropathy: C34D1 (n=5, 0) | Peripheral Neuropathy: C35D1 (n=4, 0) | Peripheral Neuropathy: C36D1 (n=1, 0) | Peripheral Neuropathy: C37D1 (n=1, 0) | Peripheral Neuropathy: EOT (n=49, 90) | Alopecia: Baseline (n=163, 162) | Alopecia: C2D1 (n=155, 132) | Alopecia: C3D1 (n=153, 106) | Alopecia: C4D1 (n=135, 91) | Alopecia: C5D1 (n=123, 74) | Alopecia: C6D1 (n=118, 70) | Alopecia: C7D1 (n=115, 52) | Alopecia: C8D1 (n=111, 43) | Alopecia: C9D1 (n=101, 37) | Alopecia: C10D1 (n=94, 33) | Alopecia: C11D1 (n=84, 25) | Alopecia: C12D1 (n=76, 23) | Alopecia: C13D1 (n=74, 21) | Alopecia: C14D1 (n=65, 19) | Alopecia: C15D1 (n=62, 16) | Alopecia: C16D1 (n=53, 12) | Alopecia: C17D1 (n=46, 11) | Alopecia: C18D1 (n=45, 11) | Alopecia: C19D1 (n=40, 9) | Alopecia: C20D1 (n=35, 8) | Alopecia: C21D1 (n=30, 8) | Alopecia: C22D1 (n=24, 7) | Alopecia: C23D1 (n=23, 3) | Alopecia: C24D1 (n=20, 3) | Alopecia: C25D1 (n=18, 3) | Alopecia: C26D1 (n=14, 3) | Alopecia: C27D1 (n=14, 2) | Alopecia: C28D1 (n=11, 2) | Alopecia: C29D1 (n=8, 2) | Alopecia: C30D1 (n=8, 1) | Alopecia: C31D1 (n=7, 0) | Alopecia: C32D1 (n=6, 0) | Alopecia: C33D1 (n=6, 0) | Alopecia: C34D1 (n=5, 0) | Alopecia: C35D1 (n=4, 0) | Alopecia: C36D1 (n=1, 0) | Alopecia: C37D1 (n=1, 0) | Alopecia: EOT (n=49, 90) | Pain in Chest: Baseline (n=163, 160) | Pain in Chest: C2D1 (n=155, 132) | Pain in Chest: C3D1 (n=153, 106) | Pain in Chest: C4D1 (n=135, 91) | Pain in Chest: C5D1 (n=123, 74) | Pain in Chest: C6D1 (n=119, 70) | Pain in Chest: C7D1 (n=115, 52) | Pain in Chest: C8D1 (n=111, 43) | Pain in Chest: C9D1 (n=101, 37) | Pain in Chest: C10D1 (n=94, 33) | Pain in Chest: C11D1 (n=84, 25) | Pain in Chest: C12D1 (n=76, 23) | Pain in Chest: C13D1 (n=74, 21) | Pain in Chest: C14D1 (n=66, 19) | Pain in Chest: C15D1 (n=62, 16) | Pain in Chest: C16D1 (n=53, 12) | Pain in Chest: C17D1 (n=46, 11) | Pain in Chest: C18D1 (n=45, 11) | Pain in Chest: C19D1 (n=40, 9) | Pain in Chest: C20D1 (n=35, 8) | Pain in Chest: C21D1 (n=30, 8) | Pain in Chest: C22D1 (n=24, 7) | Pain in Chest: C23D1 (n=23, 4) | Pain in Chest: C24D1 (n=20, 3) | Pain in Chest: C25D1 (n=18, 3) | Pain in Chest: C26D1 (n=14, 3) | Pain in Chest: C27D1 (n=14, 2) | Pain in Chest: C28D1 (n=11, 2) | Pain in Chest: C29D1 (n=8, 2) | Pain in Chest: C30D1 (n=8, 1) | Pain in Chest: C31D1 (n=7, 0) | Pain in Chest: C32D1 (n=6, 0) | Pain in Chest: C33D1 (n=6, 0) | Pain in Chest: C34D1 (n=5, 0) | Pain in Chest: C35D1 (n=4, 0) | Pain in Chest: C36D1 (n=1, 0) | Pain in Chest: C37D1 (n=1, 0) | Pain in Chest: EOT (n=49, 90) | Pain in Arm or Shoulder: Baseline (n=164, 161) | Pain in Arm or Shoulder: C2D1 (n=155, 132) | Pain in Arm or Shoulder: C3D1 (n=153, 105) | Pain in Arm or Shoulder: C4D1 (n=135, 91) | Pain in Arm or Shoulder: C5D1 (n=123, 74) | Pain in Arm or Shoulder: C6D1 (n=119, 70) | Pain in Arm or Shoulder: C7D1 (n=115, 52) | Pain in Arm or Shoulder: C8D1 (n=111, 43) | Pain in Arm or Shoulder: C9D1 (n=101, 37) | Pain in Arm or Shoulder: C10D1 (n=94, 33) | Pain in Arm or Shoulder: C11D1 (n=84, 25) | Pain in Arm or Shoulder: C12D1 (n=76, 23) | Pain in Arm or Shoulder: C13D1 (n=74, 21) | Pain in Arm or Shoulder: C14D1 (n=66, 19) | Pain in Arm or Shoulder: C15D1 (n=62, 16) | Pain in Arm or Shoulder: C16D1 (n=53, 12) | Pain in Arm or Shoulder: C17D1 (n=47, 11) | Pain in Arm or Shoulder: C18D1 (n=45, 11) | Pain in Arm or Shoulder: C19D1 (n=40, 9) | Pain in Arm or Shoulder: C20D1 (n=35, 8) | Pain in Arm or Shoulder: C21D1 (n=30, 8) | Pain in Arm or Shoulder: C22D1 (n=24, 7) | Pain in Arm or Shoulder: C23D1 (n=23, 4) | Pain in Arm or Shoulder: C24D1 (n=20, 3) | Pain in Arm or Shoulder: C25D1 (n=18, 3) | Pain in Arm or Shoulder: C26D1 (n=14, 3) | Pain in Arm or Shoulder: C27D1 (n=14, 2) | Pain in Arm or Shoulder: C28D1 (n=11, 2) | Pain in Arm or Shoulder: C29D1 (n=8, 2) | Pain in Arm or Shoulder: C30D1 (n=8, 1) | Pain in Arm or Shoulder: C31D1 (n=7, 0) | Pain in Arm or Shoulder: C32D1 (n=6, 0) | Pain in Arm or Shoulder: C33D1 (n=6, 0) | Pain in Arm or Shoulder: C34D1 (n=5, 0) | Pain in Arm or Shoulder: C35D1 (n=4, 0) | Pain in Arm or Shoulder: C36D1 (n=1, 0) | Pain in Arm or Shoulder: C37D1 (n=1, 0) | Pain in Arm or Shoulder: EOT (n=48, 90) | Pain in Other Parts: Baseline (n=163, 158) | Pain in Other Parts: C2D1 (n=153, 125) | Pain in Other Parts: C3D1 (n=152, 104) | Pain in Other Parts: C4D1 (n=134, 90) | Pain in Other Parts: C5D1 (n=123, 73) | Pain in Other Parts: C6D1 (n=118, 68) | Pain in Other Parts: C7D1 (n=115, 51) | Pain in Other Parts: C8D1 (n=111, 42) | Pain in Other Parts: C9D1 (n=100, 37) | Pain in Other Parts: C10D1 (n=92, 33) | Pain in Other Parts: C11D1 (n=83, 25) | Pain in Other Parts: C12D1 (n=74, 23) | Pain in Other Parts: C13D1 (n=74, 21) | Pain in Other Parts: C14D1 (n=66, 19) | Pain in Other Parts: C15D1 (n=61, 16) | Pain in Other Parts: C16D1 (n=53, 12) | Pain in Other Parts: C17D1 (n=46, 11) | Pain in Other Parts: C18D1 (n=45, 11) | Pain in Other Parts: C19D1 (n=40, 9) | Pain in Other Parts: C20D1 (n=35, 8) | Pain in Other Parts: C21D1 (n=30, 8) | Pain in Other Parts: C22D1 (n=24, 7) | Pain in Other Parts: C23D1 (n=23, 4) | Pain in Other Parts: C24D1 (n=20, 3) | Pain in Other Parts: C25D1 (n=18, 3) | Pain in Other Parts: C26D1 (n=14, 3) | Pain in Other Parts: C27D1 (n=14, 2) | Pain in Other Parts: C28D1 (n=11, 2) | Pain in Other Parts: C29D1 (n=8, 2) | Pain in Other Parts: C30D1 (n=8, 1) | Pain in Other Parts: C31D1 (n=7, 0) | Pain in Other Parts: C32D1 (n=6, 0) | Pain in Other Parts: C33D1 (n=6, 0) | Pain in Other Parts: C34D1 (n=5, 0) | Pain in Other Parts: C35D1 (n=4, 0) | Pain in Other Parts: C36D1 (n=1, 0) | Pain in Other Parts: C37D1 (n=1, 0) | Pain in Other Parts: EOT (n=49, 90) |
|---|
| Chemotherapy | 26.9 | 28.6 | 28.0 | 27.5 | 24.8 | 25.2 | 24.4 | 22.0 | 19.5 | 21.5 | 20.4 | 22.7 | 26.5 | 26.3 | 22.9 | 22.2 | 30.3 | 26.3 | 23.5 | 34.7 | 25.0 | 27.0 | 52.8 | 48.1 | 40.7 | 44.4 | 55.6 | 61.1 | 50.0 | 77.8 | NA | NA | NA | NA | NA | NA | NA | 35.6 | 42.2 | 34.8 | 32.4 | 27.1 | 25.7 | 30.0 | 26.3 | 22.5 | 25.2 | 20.2 | 18.7 | 23.2 | 27.0 | 24.6 | 20.8 | 22.2 | 27.3 | 18.2 | 14.8 | 29.2 | 33.3 | 28.6 | 33.3 | 44.4 | 44.4 | 33.3 | 50.0 | 50.0 | 33.3 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 37.4 | 3.7 | 3.5 | 2.2 | 1.5 | 0.9 | 3.8 | 1.3 | 2.3 | 2.7 | 3.0 | 4.0 | 5.8 | 4.8 | 0.0 | 0.0 | 5.6 | 9.1 | 3.0 | 3.7 | 8.3 | 4.2 | 9.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | NA | NA | NA | NA | NA | NA | NA | 4.8 | 6.4 | 9.1 | 9.4 | 10.3 | 9.6 | 10.5 | 7.7 | 10.9 | 10.8 | 12.1 | 9.3 | 8.7 | 9.5 | 7.0 | 14.6 | 8.3 | 6.1 | 12.1 | 7.4 | 12.5 | 4.2 | 7.1 | 16.7 | 0.0 | 0.0 | 11.1 | 16.7 | 0.0 | 16.7 | 0.0 | NA | NA | NA | NA | NA | NA | NA | 8.1 | 8.6 | 9.8 | 9.7 | 8.1 | 7.7 | 10.0 | 5.1 | 6.2 | 7.2 | 6.1 | 4.0 | 7.2 | 6.3 | 7.0 | 4.2 | 2.8 | 6.1 | 3.0 | 0.0 | 8.3 | 8.3 | 0.0 | 8.3 | 0.0 | 11.1 | 11.1 | 16.7 | 16.7 | 16.7 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 8.5 | 17.7 | 21.5 | 18.2 | 21.6 | 21.2 | 18.1 | 21.8 | 24.0 | 29.7 | 27.3 | 24.0 | 33.3 | 33.3 | 29.8 | 25.0 | 25.0 | 27.3 | 30.3 | 22.2 | 33.3 | 29.2 | 28.6 | 41.7 | 44.4 | 44.4 | 22.2 | 66.7 | 33.3 | 50.0 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 21.9 | 16.9 | 36.6 | 30.5 | 24.9 | 23.9 | 23.3 | 19.9 | 18.6 | 16.2 | 14.1 | 16.0 | 20.3 | 12.7 | 15.8 | 8.3 | 13.9 | 18.2 | 18.2 | 18.5 | 25.0 | 16.7 | 14.3 | 22.2 | 33.3 | 33.3 | 44.4 | 33.3 | 50.0 | 33.3 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 33.3 | 24.0 | 23.7 | 23.3 | 19.8 | 17.1 | 16.2 | 16.7 | 14.0 | 17.1 | 18.2 | 20.0 | 23.2 | 23.8 | 22.8 | 18.7 | 16.7 | 21.2 | 24.2 | 18.5 | 29.2 | 25.0 | 26.2 | 41.7 | 33.3 | 33.3 | 33.3 | 50.0 | 50.0 | 50.0 | 66.7 | NA | NA | NA | NA | NA | NA | NA | 28.5 | 19.5 | 19.9 | 17.5 | 14.3 | 13.1 | 17.1 | 17.3 | 20.2 | 23.4 | 25.3 | 24.0 | 29.0 | 25.4 | 29.8 | 25.0 | 16.7 | 21.2 | 30.3 | 18.5 | 25.0 | 29.2 | 21.4 | 33.3 | 44.4 | 33.3 | 22.2 | 50.0 | 33.3 | 66.7 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 21.9 | 31.4 | 25.9 | 21.2 | 21.5 | 20.5 | 18.1 | 16.3 | 22.2 | 24.3 | 28.3 | 24.0 | 24.6 | 31.7 | 24.6 | 25.0 | 38.9 | 24.2 | 33.3 | 25.9 | 29.2 | 29.2 | 40.5 | 41.7 | 11.1 | 44.4 | 33.3 | 50.0 | 33.3 | 16.7 | 33.3 | NA | NA | NA | NA | NA | NA | NA | 29.6 |
,| Crizotinib | 27.2 | 17.6 | 17.9 | 16.2 | 16.9 | 15.2 | 15.6 | 14.7 | 13.9 | 15.4 | 15.1 | 13.7 | 12.8 | 14.8 | 13.2 | 12.6 | 12.3 | 14.1 | 14.4 | 13.7 | 12.6 | 10.6 | 13.8 | 14.4 | 15.4 | 14.3 | 15.1 | 11.1 | 12.5 | 9.7 | 15.9 | 18.5 | 18.5 | 20.0 | 16.7 | 22.2 | 11.1 | 21.8 | 38.2 | 23.0 | 23.5 | 19.8 | 18.4 | 14.6 | 15.9 | 13.2 | 13.5 | 14.2 | 12.9 | 14.5 | 14.0 | 13.1 | 11.8 | 13.8 | 6.4 | 13.3 | 12.5 | 10.5 | 13.3 | 8.3 | 11.6 | 8.3 | 5.6 | 2.4 | 7.1 | 18.2 | 8.3 | 20.8 | 19.0 | 16.7 | 11.1 | 20.0 | 33.3 | 33.3 | 33.3 | 25.9 | 2.4 | 1.7 | 0.9 | 1.0 | 0.3 | 0.6 | 0.0 | 0.9 | 0.3 | 0.4 | 2.4 | 0.9 | 2.3 | 0.5 | 1.1 | 0.6 | 0.0 | 1.5 | 0.0 | 1.0 | 0.0 | 0.0 | 1.4 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.7 | 5.5 | 8.0 | 7.0 | 8.1 | 5.1 | 4.8 | 5.2 | 3.0 | 4.8 | 6.4 | 4.8 | 3.9 | 4.5 | 4.5 | 5.4 | 6.3 | 3.5 | 5.2 | 4.2 | 7.6 | 4.4 | 5.6 | 5.1 | 6.7 | 0.0 | 4.8 | 7.1 | 6.1 | 8.3 | 8.3 | 9.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 3.4 | 7.1 | 8.2 | 7.6 | 6.2 | 6.0 | 7.0 | 4.1 | 3.2 | 5.0 | 4.3 | 3.2 | 3.5 | 4.1 | 3.0 | 3.8 | 4.4 | 2.8 | 3.7 | 4.2 | 4.8 | 3.3 | 2.8 | 2.9 | 5.0 | 0.0 | 9.5 | 2.4 | 6.1 | 8.3 | 0.0 | 4.8 | 5.6 | 0.0 | 6.7 | 8.3 | 0.0 | 0.0 | 4.8 | 14.0 | 18.1 | 17.6 | 15.9 | 15.2 | 13.7 | 13.0 | 10.8 | 11.2 | 11.3 | 11.1 | 11.4 | 10.4 | 10.6 | 8.6 | 10.3 | 12.1 | 11.9 | 9.2 | 12.4 | 11.1 | 8.3 | 8.7 | 3.3 | 9.3 | 16.7 | 9.5 | 15.2 | 12.5 | 16.7 | 19.0 | 11.1 | 11.1 | 20.0 | 25.0 | 0.0 | 0.0 | 10.2 | 17.4 | 9.5 | 7.6 | 8.9 | 6.0 | 4.2 | 4.9 | 3.9 | 4.0 | 4.6 | 4.0 | 4.4 | 6.3 | 3.6 | 4.8 | 6.3 | 5.1 | 3.7 | 5.8 | 3.8 | 7.8 | 2.8 | 1.4 | 6.7 | 9.3 | 7.1 | 16.7 | 6.1 | 16.7 | 12.5 | 9.5 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 6.8 | 18.8 | 9.5 | 7.0 | 7.4 | 6.8 | 6.2 | 7.5 | 5.1 | 5.9 | 6.7 | 6.3 | 5.3 | 6.3 | 7.6 | 5.9 | 3.8 | 7.2 | 5.9 | 5.0 | 5.7 | 5.6 | 4.2 | 3.6 | 1.7 | 5.6 | 7.1 | 4.8 | 9.1 | 0.0 | 4.2 | 9.5 | 0.0 | 0.0 | 6.7 | 8.3 | 0.0 | 0.0 | 17.0 | 16.3 | 9.0 | 8.1 | 6.9 | 6.2 | 6.7 | 6.4 | 6.9 | 5.6 | 7.4 | 6.0 | 6.6 | 5.9 | 7.6 | 5.4 | 5.0 | 3.5 | 8.1 | 6.7 | 9.5 | 7.8 | 2.8 | 0.7 | 3.3 | 1.9 | 7.1 | 4.8 | 0.0 | 0.0 | 0.0 | 0.0 | 11.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 11.1 | 23.1 | 15.0 | 11.4 | 12.7 | 14.4 | 10.7 | 11.3 | 10.5 | 10.7 | 9.8 | 12.4 | 12.2 | 10.8 | 11.6 | 9.8 | 10.7 | 13.8 | 10.4 | 14.2 | 13.3 | 21.1 | 12.5 | 5.1 | 6.7 | 9.3 | 23.8 | 16.7 | 6.1 | 4.2 | 12.5 | 9.5 | 5.6 | 0.0 | 6.7 | 0.0 | 0.0 | 0.0 | 18.4 |
European Quality of Life - 5 Dimensional (EQ-5D) Visual Analog Scale (VAS)
EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single index value. 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. (NCT00932893)
Timeframe: Baseline, Day 1 of each cycle until disease progression, end of treatment (up to 112 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=164, 161) | C2D1 (n=153, 131) | C3D1 (n=153, 105) | C4D1 (n=135, 90) | C5D1 (n=122, 74) | C6D1 (n=120, 70) | C7D1 (n=115, 52) | C8D1 (n=110, 43) | C9D1 (n=101, 37) | C10D1 (n=94, 33) | C11D1 (n=84, 25) | C12D1 (n=77, 23) | C13D1 (n=73, 21) | C14D1 (n=66, 19) | C15D1 (n=62, 16) | C16D1 (n=53, 12) | C17D1 (n=47, 11) | C18D1 (n=45, 11) | C19D1 (n=40, 9) | C20D1 (n=35, 8) | C21D1 (n=30, 8) | C22D1 (n=24, 7) | C23D1 (n=23, 4) | C24D1 (n=20, 3) | C25D1 (n=18, 3) | C26D1 (n=14, 3) | C27D1 (n=14, 2) | C28D1 (n=11, 2) | C29D1 (n=8, 2) | C30D1 (n=8, 1) | C31D1 (n=7, 0) | C32D1 (n=6, 0) | C33D1 (n=6, 0) | C34D1 (n=5, 0) | C35D1 (n=4, 0) | C36D1 (n=1, 0) | C37D1 (n=1, 0) | EOT (n=49, 90) |
|---|
| Chemotherapy | 66.76 | 66.33 | 65.84 | 69.13 | 68.12 | 69.71 | 70.63 | 72.30 | 72.27 | 74.27 | 77.24 | 74.83 | 73.00 | 74.11 | 77.44 | 79.00 | 81.73 | 78.91 | 78.00 | 76.75 | 73.63 | 72.21 | 54.00 | 62.00 | 63.67 | 63.00 | 50.00 | 55.00 | 45.00 | 40.00 | NA | NA | NA | NA | NA | NA | NA | 58.34 |
,| Crizotinib | 64.09 | 69.19 | 73.13 | 73.78 | 75.27 | 75.79 | 77.02 | 74.72 | 74.45 | 75.49 | 76.32 | 76.95 | 76.38 | 78.77 | 77.71 | 75.32 | 75.09 | 75.87 | 76.85 | 72.66 | 74.13 | 77.54 | 75.48 | 71.40 | 75.61 | 72.14 | 66.57 | 72.36 | 71.38 | 69.50 | 68.57 | 65.83 | 67.50 | 68.00 | 72.25 | 90.00 | 85.00 | 68.33 |
Overall Survival Probability at Months 6 and 12
Overall survival probability at Month 6 and 12 was defined as the probability of survival at 6 and 12 months respectively, after the randomization of study treatment. The survival probability was estimated using the Kaplan-Meier method. (NCT00932893)
Timeframe: Month 6, 12
| Intervention | percent chance of survival (Number) |
|---|
| Month 6 | Month 12 |
|---|
| Chemotherapy | 83.8 | 66.7 |
,| Crizotinib | 86.6 | 70.4 |
Plasma Concentration of Crizotinib
Only participants receiving crizotinib were to be analyzed for this outcome measure as per planned analysis. (NCT00932893)
Timeframe: Pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, and Day 1 of Cycles 2, 3, 5
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Day 1 (n=15) | Cycle 1 Day 15 (n=92) | Cycle 2 Day 1 (n=62) | Cycle 3 Day 1 (n=61) | Cycle 5 Day 1 (n=47) |
|---|
| Crizotinib | NA | 298 | 293 | 306 | 291 |
Plasma Concentration of Soluble c-Met Ectodomain and Hepatocyte Growth Factor Scatter Proteins
Descriptive statistics (absolute value and change from baseline as measured by ratio to baseline) for each best overall response category (CR, PR, SD, PD or combined) have been used to summarize the data from optional soluble c-Met ectodomain assays for crizotinib treated patients. (NCT00932893)
Timeframe: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 2, end of treatment (up to 112 weeks)
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Baseline (N = 81) | Cycle 2 Day 1 6-hour post dose (N = 69) | End of treatment (N = 40) |
|---|
| Overall Values | 1428.3 | 1683.0 | 1751.8 |
Number of Participants With Categorical Maximum QTcF for Crizotinib
QT interval corrected using Fridericia's formula (QTcF): QT interval (time corresponding to the beginning of depolarization to re-polarization of the ventricles) divided by cube root of RR interval. Maximum QTcF was categorized as less than (<) 450 milliseconds (msec), 450 msec to <480 msec, 480 msec to <500 msec, and more than or equal to (>=) 500 msec. A participant is reported only once under the maximum QTcF interval observed at any of the time-points. Only participants receiving crizotinib were to be analyzed for this outcome measure as per planned analysis. (NCT00932893)
Timeframe: Pre-dose on Day 1 of Cycle 1, 2 to 6 hours post-dose on Day 1 of Cycle 1, 2
| Intervention | participants (Number) |
|---|
| <450 msec | 450 msec to <480 msec | 480 msec to <500 msec | >=500 msec |
|---|
| Crizotinib | 137 | 9 | 1 | 8 |
t1/2 of Total Serum Trastuzumab
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | days (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 8.12 | 9.91 |
,| MBC: T-DM1 2.4 mg/kg | 6.44 | 6.67 |
,| MBC: T-DM1 3.6 mg/kg | 6.38 | 7.83 |
CL of Total Serum Trastuzumab
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | mL/day/kg (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 4.22 | 3.38 |
,| MBC: T-DM1 2.4 mg/kg | 6.78 | 3.32 |
,| MBC: T-DM1 3.6 mg/kg | 5.45 | 3.71 |
t1/2 of Plasma Docetaxel
Docetaxel infusion duration = 1 hr (as per SmPC) (NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1. Cycle 2: pre-dose (Hr 0), 0.5 hr and 59 min after start of infusion, 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1 (1 cycle = 21 days)
| Intervention | hours (hr) (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: Docetaxel 100 mg/m^2 | 8.76 | 7.24 |
,| LABC: Docetaxel 60 mg/m^2 | 4.25 | 5.9 |
,| LABC: Docetaxel 75 mg/m^2 | 8.29 | 6.69 |
,| MBC: Docetaxel 60 mg/m^2 | 5.17 | 7.88 |
,| MBC: Docetaxel 75 mg/m^2 | 6.83 | 7.7 |
Clearance (CL) of Serum Trastuzumab Emtansine
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | milliliters/day/kilogram (mL/day/kg) (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 8.48 | 7.68 |
,| MBC: T-DM1 2.4 mg/kg | 8.94 | 5.21 |
,| MBC: T-DM1 3.6 mg/kg | 8.87 | 7.16 |
Cmax of Plasma Docetaxel
Docetaxel infusion duration = 1 hr (as per summary of product characteristics [SmPC]) (NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1. Cycle 2: pre-dose (Hr 0), 0.5 hr and 59 min after start of infusion, 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1 (1 cycle = 21 days)
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: Docetaxel 100 mg/m^2 | 2950 | 2790 |
,| LABC: Docetaxel 60 mg/m^2 | 1470 | 1590 |
,| LABC: Docetaxel 75 mg/m^2 | 1710 | 1960 |
,| MBC: Docetaxel 60 mg/m^2 | 1300 | 1320 |
,| MBC: Docetaxel 75 mg/m^2 | 500 | 791 |
Cmax of Plasma N2'-Deacetyl-N2'-(3-mercapto-1-oxopropyl)-Maytansine (DM1)
DM1 is the metabolite of trastuzumab emtansine. (NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | nanograms per milliliter (ng/mL) (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 4.51 | 4.65 |
,| MBC: T-DM1 2.4 mg/kg | 3.55 | 3.34 |
,| MBC: T-DM1 3.6 mg/kg | 3.42 | 3.9 |
t1/2 of Plasma DM1
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | days (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 1.87 | 3.32 |
,| MBC: T-DM1 2.4 mg/kg | 1.12 | 3.75 |
,| MBC: T-DM1 3.6 mg/kg | 1.2 | 2.91 |
Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) - MBC and LABC Population
An AE is any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event. (NCT00934856)
Timeframe: Baseline up to 28 days after last dose for MBC participants and for LABC participants who could not undergo surgery, and up to 6 weeks post-surgery for LABC participants who underwent surgery (maximum up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| AEs | SAEs |
|---|
| LABC: T-DM1 + Doc (Doublet Regimen) | 100 | 22.5 |
,| LABC: T-DM1 + Doc + Pertuzumab (Triplet Regimen) | 100 | 27.3 |
,| MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (Over 2 Days) | 100 | 33.3 |
,| MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (Same Day) | 100 | 66.7 |
,| MBC: T-DM1 2.4 mg/kg + Doc 75 mg/m^2 (Over 2 Days) | 100 | 33.3 |
,| MBC: T-DM1 3.6 mg/kg + Doc 60 mg/m^2 (Same Day) | 100 | 40.0 |
Number of Participants With Anti-Therapeutic Antibody (ATA) Response to Trastuzumab - MBC and LABC Population
Number of participants with ATA response was reported. Data for this outcome measure was planned to be reported for overall MBC and LABC participants and not by individual treatment arms. (NCT00934856)
Timeframe: Baseline (Day 1 of Cycle 1), Post baseline (at first follow-up visit [28 days after last dose of study drug][up to approximately 145 weeks])
| Intervention | participants (Number) |
|---|
| Baseline | Post-baseline |
|---|
| Overall MBC and LABC Participants | 3 | 3 |
Cmax of Total Serum Trastuzumab
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 120 | 113 |
,| MBC: T-DM1 2.4 mg/kg | 88.7 | 85.8 |
,| MBC: T-DM1 3.6 mg/kg | 89.2 | 97.7 |
Volume of Distribution at Steady State (Vss) of Serum Trastuzumab Emtansine
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | mL/kg (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 33.2 | 28.8 |
,| MBC: T-DM1 2.4 mg/kg | 22.1 | 17.7 |
,| MBC: T-DM1 3.6 mg/kg | 33.2 | 31.4 |
AUCinf of Plasma DM1
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | day*ng/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 9.38 | 18.5 |
,| MBC: T-DM1 2.4 mg/kg | 5.72 | 17.8 |
,| MBC: T-DM1 3.6 mg/kg | 5.01 | 20 |
AUCinf of Plasma Docetaxel
Docetaxel infusion duration = 1 hr (as per SmPC) (NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1. Cycle 2: pre-dose (Hr 0), 0.5 hr and 59 min after start of infusion, 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1 (1 cycle = 21 days)
| Intervention | hr*ng/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: Docetaxel 100 mg/m^2 | 4020 | 3840 |
,| LABC: Docetaxel 60 mg/m^2 | 1540 | 3260 |
,| LABC: Docetaxel 75 mg/m^2 | 2140 | 2420 |
,| MBC: Docetaxel 60 mg/m^2 | 1560 | 1710 |
,| MBC: Docetaxel 75 mg/m^2 | 1050 | 1700 |
AUCinf of Total Serum Trastuzumab
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | day*mcg/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 1210 | 1570 |
,| MBC: T-DM1 2.4 mg/kg | 785 | 809 |
,| MBC: T-DM1 3.6 mg/kg | 707 | 1040 |
CL of Plasma Docetaxel
Docetaxel infusion duration = 1 hr (as per SmPC) (NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1. Cycle 2: pre-dose (Hr 0), 0.5 hr and 59 min after start of infusion, 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1 (1 cycle = 21 days)
| Intervention | liters/hour/square meter (L/hr/m^2) (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: Docetaxel 100 mg/m^2 | 30.5 | 27.9 |
,| LABC: Docetaxel 60 mg/m^2 | 42.8 | 32.6 |
,| LABC: Docetaxel 75 mg/m^2 | 39.5 | 33.6 |
,| MBC: Docetaxel 60 mg/m^2 | 58.3 | 51.2 |
,| MBC: Docetaxel 75 mg/m^2 | 82.2 | 59 |
Vss of Total Serum Trastuzumab
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | mL/kg (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 36.5 | 35.2 |
,| MBC: T-DM1 2.4 mg/kg | 27 | 24.6 |
,| MBC: T-DM1 3.6 mg/kg | 41.3 | 36.4 |
Percentage of Participants With a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) - MBC Population
BOR was defined as CR or PR recorded from baseline until disease progression/recurrence according to RECIST v1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of LDs of the TLs, taking as a reference the baseline (BL) sum of LDs. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with BOR rate was calculated as the (number of participants with CR or PR) divided by (total number of participants), and then multiplied by 100. The 95% confidence interval (Cl) was determined using the Pearson-Clopper method. (NCT00934856)
Timeframe: Baseline until disease progression or recurrence (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Overall MBC Participants | 80.0 |
Time to Treatment Failure (TTF) - MBC Population
TTF was defined as the time interval between the date of start of treatment and the date of PD, death from any cause, withdrawal from study treatment, or initiation of non-protocol anti-cancer therapy, whichever occurred first. Participants without an event at the time of the analysis were censored at the date of the last follow-up assessment. Median TTF was estimated using the Kaplan-Meier method. (NCT00934856)
Timeframe: Baseline until end of treatment (up to 39.8 months)
| Intervention | months (Median) |
|---|
| Overall MBC Participants | 13.8 |
PFS - MBC Population
PFS was defined as the time interval between the date of the start of treatment and the date of first documentation of PD or death from any cause, whichever occurred first. Response was based on RECIST v1.0. For TLs, PD was at least a 20 % increase in the sum of LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. For NTLs, PD was the appearance of one or more new lesions and/or unequivocal progression of existing NTLs. Median PFS time was calculated using Kaplan-Meier estimates. Data for participants without PD or death was censored at the time of the last response assessment. (NCT00934856)
Timeframe: Baseline until disease progression or death (up to approximately 3 years)
| Intervention | months (Median) |
|---|
| Overall MBC Participants | 13.8 |
Duration of Response - MBC Population
Duration of response was calculated for participants with CR or PR based on the RECIST v1.0 criteria. Duration of response was defined as the time interval between the date the CR or PR was first recorded and the date on which PD was first noted or date of death, whichever occurred first. Participants with no documented PD after CR or PR were censored at the last date at which they were known to have had the CR or PR, respectively. Median duration of response was estimated using the Kaplan-Meier method. (NCT00934856)
Timeframe: Baseline until disease progression, recurrence or death (up to approximately 3 years)
| Intervention | months (Median) |
|---|
| Overall MBC Participants | 12.4 |
Percentage of Participants With a BOR of CR or PR - LABC Population
BOR was defined as CR or PR recorded from baseline until disease progression/recurrence according to RECIST v1.0 criteria. For TLs, CR was defined as the disappearance of all TLs, and PR was defined as at least a 30% decrease in the sum of LDs of the TLs, taking as a reference the baseline (BL) sum of LDs. For NTLs, CR was defined as the disappearance of all NTLs and normalization of tumor marker levels. Percentage of participants with BOR rate was calculated as the (number of participants with CR or PR) divided by (total number of participants), and then multiplied by 100. The 95% Cl was determined using the Pearson-Clopper method. (NCT00934856)
Timeframe: Baseline until disease progression, recurrence or death (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| LABC: T-DM1 + Doc (Doublet Regimen) | 70.0 |
| LABC: T-DM1 + Doc + Pertuzumab (Triplet Regimen) | 51.5 |
Percentage of Participants With CR or PR or Stable Disease (SD) for at Least 6 Months [Clinical Benefit Rate (CBR)] - MBC Population
CBR was defined as percentage of participants experiencing SD of at least 6 months from the start of treatment plus CR or PR according to the RECIST v1.0 criteria. For TLs: CR- disappearance of all TLs. PR- at least 30% decrease in the sum of LDs of the TLs, taking as a reference the BL sum of LDs. PD- at least 20% increase in the sum of LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. SD- neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. For NTLs: CR- disappearance of all NTLs and normalization of tumor marker levels. SD- persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits. Percentage of participants= number of participants with CR/PR/SD divided by total number of participants, and then multiplied by 100. 95% CI was determined using the Pearson-Clopper method. (NCT00934856)
Timeframe: Baseline until disease progression, recurrence or death (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Overall MBC Participants | 92.0 |
Percentage of Participants With Pathological CR (pCR) - LABC Population
The pCR was defined as the absence of invasive neoplastic cells at microscopic examination of the tumor remnants and lymph nodes after surgery following primary systemic therapy. (NCT00934856)
Timeframe: Within 6 weeks of post-surgery (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| LABC: T-DM1 + Doc (Doublet Regimen) | 60.0 |
| LABC: T-DM1 + Doc + Pertuzumab (Triplet Regimen) | 60.6 |
Percentage of Participants With Progression-Free Survival (PFS) Event - MBC Population
PFS was defined as the time interval between the date of the start of treatment and the date of first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 (v1.0). For target lesions (TLs), PD was 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 one or more lesions. For non-target lesions (NTLs), PD was the appearance of one or more new lesions and/or unequivocal progression of existing NTLs. Data for participants without PD or death was censored at the time of the last response assessment. Percentage of participants with PFS event was calculated as the (number of participants with PFS event [PD or death]) divided by (total number of participants), and then multiplied by 100. (NCT00934856)
Timeframe: Baseline until disease progression or death (up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Overall MBC Participants | 60.0 |
Number of Participants With Dose Limiting Toxicity (DLT) - MBC and LABC Feasibility Population
DLTs included (as per National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] grading): Grade 4 thrombocytopenia, thrombocytopenia of any grade with concurrent hemorrhage or requiring blood platelet transfusion, or thrombocytopenia not recovered by Day 21 to at least 100,000/microliter (mcL); Grade 4 neutropenia lasting for more than 7 days; Febrile neutropenia; Grade greater than or equal to (>/=) 3 neurotoxicity in the form of peripheral neuropathy or peripheral neurotoxicity not improving to baseline or Grade less than or equal to (/= 3 except for alopecia, fever, and chills, not improving to baseline or Grade NCT00934856)
Timeframe: Cycle 1 (up to 21 days)
| Intervention | participants (Number) |
|---|
| MBC: T-DM1 2.4 mg/kg + Doc 75 mg/m^2 (Over 2 Days) | 2 |
| MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (Over 2 Days) | 1 |
| MBC: T-DM1 2.4 mg/kg + Doc 60 mg/m^2 (Same Day) | 0 |
| MBC: T-DM1 3.6 mg/kg + Doc 60 mg/m^2 (Same Day) | 1 |
| LABC: T-DM1 + Doc (Doublet Regimen) | 2 |
| LABC: T-DM1 + Doc + Pertuzumab (Triplet Regimen) | 2 |
Vss of Plasma Docetaxel
Docetaxel infusion duration = 1 hr (as per SmPC) (NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1. Cycle 2: pre-dose (Hr 0), 0.5 hr and 59 min after start of infusion, 0.25, 0.5, 1, 2, 4, 8, 23 hrs post EOI of docetaxel on Day 1 (1 cycle = 21 days)
| Intervention | liters per square meter (L/m^2) (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: Docetaxel 100 mg/m^2 | 116 | 84.8 |
,| LABC: Docetaxel 60 mg/m^2 | 75 | 93.2 |
,| LABC: Docetaxel 75 mg/m^2 | 126 | 79 |
,| MBC: Docetaxel 60 mg/m^2 | 203 | 253 |
,| MBC: Docetaxel 75 mg/m^2 | 530 | 380 |
Maximum Observed Concentration (Cmax) of Serum Trastuzumab Emtansine
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hour [Hr] 0), 0.25, 4 hrs post end of infusion (EOI) of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 85.7 | 80.2 |
,| MBC: T-DM1 2.4 mg/kg | 78.6 | 78.7 |
,| MBC: T-DM1 3.6 mg/kg | 76.2 | 93.7 |
Apparent Terminal Half-Life (t1/2) of Serum Trastuzumab Emtansine
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | days (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 3.46 | 3.62 |
,| MBC: T-DM1 2.4 mg/kg | 2.79 | 3.14 |
,| MBC: T-DM1 3.6 mg/kg | 3.45 | 3.85 |
Percentage of Participants With Treatment Failure - MBC Population
Treatment failure was defined as the discontinuation of treatment for any reason, including the following qualifying events: PD, death from any cause, withdrawal from study treatment, or initiation of nonprotocol anti-cancer therapy. Percentage of participants with treatment failure was calculated as the (number of participants with treatment failure) divided by (total number of participants), and then multiplied by 100. (NCT00934856)
Timeframe: Baseline until end of treatment (up to 39.8 months)
| Intervention | percentage of participants (Number) |
|---|
| Overall MBC Participants | 64.0 |
Area Under the Concentration-Time Curve From Time 0 to Infinity (AUCinf) of Serum Trastuzumab Emtansine
(NCT00934856)
Timeframe: Cycle 1: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 2; on Days 3 and 8. Cycle 2: pre-dose (Hr 0), 0.25, 4 hrs post EOI of T-DM1 on Day 1; on Day 8 (1 cycle = 21 days) (T-DM1 infusion duration = 1.5 hrs)
| Intervention | day*mcg/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| LABC: T-DM1 3.6 mg/kg | 442 | 488 |
,| MBC: T-DM1 2.4 mg/kg | 396 | 471 |
,| MBC: T-DM1 3.6 mg/kg | 447 | 556 |
Percentage of Participants With Overall Clinical Tumor Response (CR or PR)
Overall clinical tumor response rate was defined as the percentage of evaluable participants who achieved either complete response (CR) or partial response (PR) noted on the objective status from pre-surgical staging (for arm II) or either from pre-RT or pre-surgical staging (for arm I).> CR was defined as disappearance of all non-target lesion (TL) and normalization of tumor biomarker level, all lymph nodes (LN) must be non-pathological in size (<1 cm short axis); or disappearance of all TL and normalization of tumor biomarkers, any pathological LN (whether target or non-target) must have reduction in short axis to <1 cm; or >=30% decrease in the sum of the diameters of TL taking as reference the baseline sum of the diameters. (NCT00938470)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Arm I (DOC, 5FU/O/RT, Surgery) | 32.1 |
| Arm II (5FU/O/RT, Surgery) | 33.3 |
Number of Participants Who Experienced a Maximum Grade of 3 or Above Adverse Event
Adverse events were assessed using National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. (NCT00938470)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3=Severe | Grade 4=Life threatening | Grade 5=Death |
|---|
| Arm I (DOC, 5FU/O/RT, Surgery) | 10 | 10 | 4 |
,| Arm II (5FU/O/RT, Surgery) | 12 | 7 | 4 |
Overall Survival
Overall survival was defined as the time from randomization to the time of death from any cause. Overall survival was censored at the date of last follow-up visit for patients who are still alive or loss of follow-up. (NCT00938470)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Arm I (DOC, 5FU/O/RT, Surgery) | NA |
| Arm II (5FU/O/RT, Surgery) | 18.8 |
Percentage of Participants With Pathologic Complete Response (PCR)
Pathologic complete response was defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined. (NCT00938470)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Arm I (DOC, 5FU/O/RT, Surgery) | 28.6 |
| Arm II (5FU/O/RT, Surgery) | 40.7 |
Disease-free Survival
Disease-free survival was defined as the time from randomization to the date of recurrent or death, whichever comes first. (NCT00938470)
Timeframe: Up to 2 years
| Intervention | months (Median) |
|---|
| Arm I (DOC, 5FU/O/RT, Surgery) | 31.2 |
| Arm II (5FU/O/RT, Surgery) | 17.0 |
Count of Participants With a Radiologic Response
Radiologic response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 criteria. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the diameters 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 (this includes the baseline sum if that is the smallest on study). Stable disease is neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. (NCT00942578)
Timeframe: median time of potential follow-up of 47.5 months
| Intervention | Participants (Count of Participants) |
|---|
| Confirmed radiologic PR | Complete Response | Stable Disease |
|---|
| 15 mg Lenalidomide | 3 | 0 | 1 |
,| 20 mg Lenalidomide | 2 | 2 | 0 |
,| 25 mg Lenalidomide | 20 | 0 | 3 |
Recommended Phase 2 Dose (RP2D)
The RP2D is the dose at which there are no dose-limiting toxicities (defined as a ≥grade 3 hematological toxicity related to lenalidomide). (NCT00942578)
Timeframe: 3 weeks
| Intervention | mg (Number) |
|---|
| Single Arm - 4 Drug Combination | 25 |
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) Who Were Administered the Four-Drug Combination
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in 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. (NCT00942578)
Timeframe: Date treatment consent signed to date off study, approximately 93 months and 22 days.
| Intervention | Participants (Count of Participants) |
|---|
| 15 mg Dose Lenalidomide | 14 |
| 20 mg Dose Lenalidomide | 3 |
| 25 mg Dose Lenalidomide | 46 |
Count of Participants With Dose-Limiting Toxicities (DLT)
DLT is defined as a ≥grade 3 non-hematological toxicity related to lenalidomide. (NCT00942578)
Timeframe: First 28 days of treatment.
| Intervention | Participants (Count of Participants) |
|---|
| Single Arm - 4 Drug Combination | 0 |
Survival Based on Expression of T Cell Immunoglobulin and Mucin Domain (TIM-3) on Cluster of Differentiation 8 (CD8) + T Cells
Expression of TIM-3 on CD8 + T cells was evaluated by flow cytometry. (NCT00942578)
Timeframe: 46.5 months
| Intervention | Months (Median) |
|---|
| Low expression | High expression |
|---|
| 15 mg Lenalidomide | 23.6 | NA |
,| 20 mg Lenalidomide | NA | NA |
,| 25 mg Lenalidomide | 20.2 | 12.7 |
Survival Based on Expression of Programmed Cell Death Protein 1 (PD-1) on Cluster of Differentiation 8 (CD8) + T Cells
Expression of PD-1 on CD8 + T cells was evaluated by flow cytometry. High and low expression are based on the median values. Patients with a low expression of PD-1 proteins had better survival than those with a high expression. (NCT00942578)
Timeframe: median time of potential follow-up of 47.5 months
| Intervention | Months (Median) |
|---|
| Low expression | High expression |
|---|
| 15 mg Dose Lenalidomide | 21.4 | 22.4 |
,| 20 mg Dose Lenalidomide | 17.8 | 26.1 |
,| 25 mg Dose Lenalidomide | 28.9 | 14.8 |
Count of Participants With Prostatic Antigen-Specific (PSA) Declines
PSA decline is defined as a ≥50% decline in measurable disease. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥20 mm by chest x-ray, as ≥10 mm with computed tomography, or ≥10 mm with calipers by clinical exam. (NCT00942578)
Timeframe: median time of potential follow-up of 47.5 months
| Intervention | Participants (Count of Participants) |
|---|
| Participants with PSA>30% | Participants with PSA>50% | Participants with PSA>90% | Not Evaluable |
|---|
| 15 mg Lenalidomide | 13 | 12 | 5 | 1 |
,| 20 mg Lenalidomide | 3 | 3 | 1 | 0 |
,| 25 mg Lenalidomide | 41 | 40 | 27 | 1 |
Count of Participants With Changes in Circulating Apoptotic Endothelial Cells (CAEC) From Baseline After Drug Administration
The definition of an increase is any increase (any number greater than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1. The definition of a decrease is any decrease (any number less than zero) in the percent CAEC among total peripheral blood mononuclear cells comparing each patient's percent CAEC among total peripheral blood mononuclear cells at baseline to each patient's percent CAEC among total peripheral blood mononuclear cells at cycle 3 day 1. (NCT00942578)
Timeframe: After drug administration, an average of 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Increase in CAEC after 3 months | decrease in CAEC after 3 months |
|---|
| Single Arm - 4 Drug Combination | 30 | 20 |
Event-Free Survival (EFS)
Protocol-defined events included disease recurrence or progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. EFS was estimated by Kaplan-Meier analysis and defined as the time from randomization to the first protocol-defined event. (NCT00950300)
Timeframe: Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
| Intervention | months (Median) |
|---|
| Herceptin IV + Chemotherapy | NA |
| Herceptin SC + Chemotherapy | NA |
Number of Participants With ADAs Against Recombinant Human Hyaluronidase (rHuPH20)
"Participants in the Herceptin SC arm provided PK samples for evaluation of anti-rHuPH20 antibodies. The number of participants with Treatment-induced ADAs and Treatment-enhanced ADA against rHuPH20 (an excipient unique to the SC formulation) at any time during or after treatment was reported. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result (four-fold increase of titer)." (NCT00950300)
Timeframe: Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18
| Intervention | participants (Number) |
|---|
| Treatment-induced ADA | Treatment-enhanced ADA |
|---|
| Herceptin SC + Chemotherapy | 49 | 13 |
Number of Participants With Anti-Drug Antibodies (ADAs) Against Trastuzumab
"Participants provided PK samples for evaluation of anti-trastuzumab antibodies. The number of participants with Treatment-induced ADAs and Treatment-enhanced ADA against trastuzumab at any time during or after treatment was reported. Treatment-induced ADA = a participant with negative or missing Baseline ADA result(s) and at least one positive post-Baseline ADA result. Treatment-enhanced ADA = a participant with positive ADA result at Baseline who has one or more post Baseline titer results that are at least 0.60 titer unit greater than the Baseline titer result (four-fold increase of titer)." (NCT00950300)
Timeframe: Baseline; pre-dose (0 hours) on Day 1 of Cycles 2, 5, 13, 18 (cycle length of 21 days); and Months 3, 6, 12, 18, 24, 30, 36, 42, 48, 54, 60 from last dose of Cycle 18
| Intervention | participants (Number) |
|---|
| Treatment-induced ADAs | Treatment-enhanced ADA |
|---|
| Herceptin IV + Chemotherapy | 28 | 2 |
,| Herceptin SC + Chemotherapy | 46 | 1 |
Maximum Serum Concentration (Cmax) of Trastuzumab Prior to Surgery
PK samples were obtained prior to surgery (Cycle 7). The Cmax during Cycle 7 was recorded, averaged among all participants, and expressed in μg/mL. (NCT00950300)
Timeframe: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
| Intervention | μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 221 |
| Herceptin SC + Chemotherapy | 149 |
Overall Survival (OS)
OS was estimated by Kaplan-Meier analysis and defined as the time from randomization to death from any cause. (NCT00950300)
Timeframe: Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
| Intervention | months (Median) |
|---|
| Herceptin IV + Chemotherapy | NA |
| Herceptin SC + Chemotherapy | NA |
Number of Participants With Ctrough of Trastuzumab >20 μg/mL After Surgery
Pre-dose samples were obtained after surgery (Cycle 13). The number of participants who had an observed Ctrough >20 μg/mL was reported. (NCT00950300)
Timeframe: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
| Intervention | participants (Number) |
|---|
| Herceptin IV + Chemotherapy | 216 |
| Herceptin SC + Chemotherapy | 227 |
Cmax of Trastuzumab After Surgery
PK samples were obtained after surgery (Cycle 12). The Cmax during Cycle 12 was recorded, averaged among all participants, and expressed in μg/mL. (NCT00950300)
Timeframe: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
| Intervention | μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 230 |
| Herceptin SC + Chemotherapy | 166 |
AUC21d of Trastuzumab After Surgery
PK samples were obtained after surgery (Cycle 12). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 12 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in d*μg/mL. (NCT00950300)
Timeframe: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
| Intervention | d*μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 2179 |
| Herceptin SC + Chemotherapy | 2610 |
Number of Participants With Ctrough of Trastuzumab >20 μg/mL Prior to Surgery
Pre-dose samples were obtained prior to surgery (Cycle 8). The number of participants who had an observed Ctrough >20 μg/mL was reported. (NCT00950300)
Timeframe: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
| Intervention | participants (Number) |
|---|
| Herceptin IV + Chemotherapy | 232 |
| Herceptin SC + Chemotherapy | 227 |
Observed Ctrough of Trastuzumab After Surgery
Pre-dose samples were obtained after surgery (Cycle 13). The observed Ctrough was recorded, averaged among all participants, and expressed in μg/mL. (NCT00950300)
Timeframe: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
| Intervention | μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 62.1 |
| Herceptin SC + Chemotherapy | 90.4 |
Observed Serum Trough Concentration (Ctrough) of Trastuzumab Prior to Surgery
Pre-dose samples were obtained prior to surgery (Cycle 8). The observed Ctrough was recorded, averaged among all participants, and expressed in micrograms per milliliter (μg/mL). (NCT00950300)
Timeframe: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
| Intervention | μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 57.8 |
| Herceptin SC + Chemotherapy | 78.7 |
Percentage of Participants Who Died
The percentage of participants who died at any time during the study was reported. (NCT00950300)
Timeframe: Continuously during treatment (up to 12 months); at Months 1, 3, 6 from last dose of Cycle 18 (cycle length of 21 days); then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin IV + Chemotherapy | 14.5 |
| Herceptin SC + Chemotherapy | 13.6 |
Area Under the Concentration-Time Curve From 0 to 21 Days (AUC21d) of Trastuzumab Prior to Surgery
PK samples were obtained prior to surgery (Cycle 7). Values were extrapolated beyond Day 15 to produce the area over the full 21-day cycle. The AUC21d value at Cycle 7 was calculated from trastuzumab concentration-time profiles using standard non-compartmental PK methods, averaged among all participants, and expressed in days multiplied by micrograms per milliliters (d*μg/mL). (NCT00950300)
Timeframe: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
| Intervention | d*μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 2056 |
| Herceptin SC + Chemotherapy | 2268 |
Percentage of Participants With Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0, Among Those With Measurable Disease at Baseline
Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to less than (<) 10 millimeters (mm) with no prior assessment of progressive disease (PD). PR was defined as greater than or equal to (≥) 30% decrease from Baseline in sum diameter (SD) of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. The percentage of participants with overall response of CR or PR at the end of neoadjuvant treatment was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method. (NCT00950300)
Timeframe: Tumor assessments at Baseline; on Day 1 of Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months overall)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin IV + Chemotherapy | 88.8 |
| Herceptin SC + Chemotherapy | 87.2 |
Percentage of Participants With Pathological Complete Response (pCR)
Participants were evaluated following eight cycles of treatment and after surgery to assess for pCR, defined as absence of neoplastic invasive cells in the breast according to pathologist examination. The percentage of participants with pCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method. (NCT00950300)
Timeframe: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin IV + Chemotherapy | 40.7 |
| Herceptin SC + Chemotherapy | 45.4 |
Percentage of Participants With Total Pathological Complete Response (tpCR)
Participants were evaluated following eight cycles of treatment and after surgery to assess for tpCR, defined as absence of neoplastic invasive cells in the breast and axillary lymph nodes according to pathologist examination. The percentage of participants with tpCR was reported, and the 95% CI for one-sample binomial was constructed using the Pearson-Clopper method. (NCT00950300)
Timeframe: After surgery following eight cycles of Herceptin + chemotherapy (approximately 6 months from Baseline)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin IV + Chemotherapy | 34.2 |
| Herceptin SC + Chemotherapy | 39.2 |
Predicted Ctrough of Trastuzumab After Surgery
Predicted Ctrough at pre-dose after surgery (Cycle 13) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL. (NCT00950300)
Timeframe: Pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
| Intervention | μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 51.7 |
| Herceptin SC + Chemotherapy | 80.6 |
Percentage of Participants Who Experienced a Protocol-Defined Event
Protocol-defined events included disease recurrence/progression (local, regional, distant, contralateral) or death from any cause. Imaging was performed at specified visits for up to 5 years after last dose. Thereafter, participants were followed for survival only. The percentage of participants who experienced a protocol-defined event at any time during the study was reported. (NCT00950300)
Timeframe: Screening; Day 1 of Cycle 18 (cycle length of 21 days); and Months 6, 12, 24, 36, 48, 60 from last dose of Cycle 18; then every 6 months until withdrawal for any reason (up to approximately 87 months overall)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin IV + Chemotherapy | 33.3 |
| Herceptin SC + Chemotherapy | 32.7 |
Predicted Ctrough of Trastuzumab Prior to Surgery
Predicted Ctrough at pre-dose prior to surgery (Cycle 8) was determined on the basis of a population PK model from Study BP22023 (NCT00800436). The mean predicted Ctrough was expressed in μg/mL. (NCT00950300)
Timeframe: Pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
| Intervention | μg/mL (Mean) |
|---|
| Herceptin IV + Chemotherapy | 51.4 |
| Herceptin SC + Chemotherapy | 80.3 |
Time of Maximum Serum Concentration (Tmax) of Trastuzumab Prior to Surgery
PK samples were obtained prior to surgery (Cycle 7). The Tmax during Cycle 7 was recorded, averaged among all participants, and expressed in days. (NCT00950300)
Timeframe: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 7; on Days 2, 4, 8, 15 of Cycle 7; pre-dose (0 hours) on Day 1 of Cycle 8 (cycle length of 21 days)
| Intervention | days (Mean) |
|---|
| Herceptin IV + Chemotherapy | 0.05 |
| Herceptin SC + Chemotherapy | 4.12 |
Time to Response According to RECIST Version 1.0, Among Those With Measurable Disease at Baseline
Tumor response was assessed using RECIST version 1.0. CR was defined as disappearance of all target lesions and short-axis reduction of any pathological lymph nodes to <10 mm with no prior assessment of PD. PR was defined as ≥30% decrease from Baseline in SD of target lesions with no prior assessment of PD. PD was defined as ≥20% relative increase and ≥5 mm of absolute increase in the SD of target lesions, taking as reference the smallest SD recorded since treatment started; or appearance of 1 or more new lesions. Time to response was defined as the time from first dose of study medication to the first assessment of CR or PR, which was the date the response was first documented by objective evidence, among participants with an overall response of CR or PR. (NCT00950300)
Timeframe: Tumor assessments at Baseline; on Day 1 Cycles 3, 5, 7 (cycle length of 21 days); and at time of surgery following eight cycles of chemotherapy (approximately 6 months overall)
| Intervention | weeks (Median) |
|---|
| Herceptin IV + Chemotherapy | 6.14 |
| Herceptin SC + Chemotherapy | 6.14 |
Tmax of Trastuzumab After Surgery
PK samples were obtained after surgery (Cycle 12). The Tmax during Cycle 12 was recorded, averaged among all participants, and expressed in days. (NCT00950300)
Timeframe: Pre-dose (0 hours) and at end of 30-minute infusion (Herceptin IV only) on Day 1 of Cycle 12; on Days 2, 4, 8, 15 of Cycle 12; pre-dose (0 hours) on Day 1 of Cycle 13 (cycle length of 21 days)
| Intervention | days (Mean) |
|---|
| Herceptin IV + Chemotherapy | 0.06 |
| Herceptin SC + Chemotherapy | 4.08 |
Change in 18F-Fluorodeoxyglucose (FDG) Uptake
Will be calculated by subtracting the baseline FDG uptake from the post-cycle 2 uptake (as measured by SULmax). (NCT00963807)
Timeframe: Baseline and 6 weeks
| Intervention | SULmax (Mean) |
|---|
| Treatment (Docetaxel, Cisplatin, Dexamethasone, and Surgery) | -3.8 |
Overall Response Rate Reported as a Proportion of the Total Number of Patients Who Received at Least One Cycle of Therapy Assessed Using Response Evaluation Criteria in Solid Tumors (RECIST)
RECIST version 1.1 was utilized for this outcome measure. A detailed description of RECIST 1.1 can be found here: Nishino M, Jackman DM, Hatabu H, Yeap BY, Cioffredi LA, Yap JT, et al. New Response Evaluation Criteria in Solid Tumors (RECIST) guidelines for advanced non-small cell lung cancer: comparison with original RECIST and impact on assessment of tumor response to targeted therapy. AJR Am J Roentgenol 2010;195:W221-8. (NCT00963807)
Timeframe: Up to 6 weeks
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Docetaxel, Cisplatin, Dexamethasone, and Surgery) | 33 |
Change in FLT Uptake in Responders and Non-responders
Unadjusted analysis will be performed utilizing students t-tests. If the data appears non-normal, the Wilcox on rank-sum test will be used rather than the t-test. Adjusted analysis will be performed utilizing logistic regression. (NCT00963807)
Timeframe: Baseline and 6 weeks
| Intervention | SULmax (Mean) |
|---|
| Responders | -1.8 |
| Non-Responders | 1.2 |
Change in FLT Uptake
Will be calculated by subtracting the uptake of the scan after the second cycle of chemotherapy from the uptake of the pre-treatment scan. (NCT00963807)
Timeframe: Baseline and 6 weeks
| Intervention | SULmax (Mean) |
|---|
| Treatment (Docetaxel, Cisplatin, Dexamethasone, and Surgery) | 0.2 |
Change in 18F-Fluorothymidine (FLT) Uptake
Will be calculated by subtracting the uptake of the scan after the first cycle of chemotherapy from the uptake of the pre-treatment scan.. Change in FLT uptake will be measured using the maximum standard uptake value adjusted for lean body mass (SULmax), which is a measure of how much radiotracer (in this case FLT) is being consumed by cells. (NCT00963807)
Timeframe: Baseline and 3 weeks
| Intervention | SULmax (Mean) |
|---|
| Treatment (Docetaxel, Cisplatin, Dexamethasone, and Surgery) | -0.4 |
Best Response
The number of patients with a response will be assessed using the RECIST criteria of complete response (the disappearance of all target lesions); partial response (at least a 30% decrease in the diameter of lesions); progressive disease at least a 20% increase in the diameter of lesions); or stable disease(neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease) (NCT00970684)
Timeframe: 1 year
| Intervention | participants (Number) |
|---|
| Stable Disease | Partial Response | Progressive Disease |
|---|
| Bevacizumab, Docetaxel, and Gemcitabine | 2 | 9 | 1 |
Progression Free Survival(PFS)
PFS is defined as time to death or first occurrence of documented disease progression assessed by the investigator as per the RECIST guidelines (at lease a 20% increase in the diameter of a lesion, in addition to an absolute increase of 5mm). If no deaths occur prior to progression, this measure will be the same as the median time to progression. (NCT00970684)
Timeframe: 1 year
| Intervention | months (Median) |
|---|
| Bevacizumab, Docetaxel, and Gemcitabine | 5.6 |
Safety: Percentage of Participants With Asymptomatic Left Ventricular Ejection Fraction (LVEF) Events
Percentage of participants with LVEF events without signs or symptoms of cardiac events. (NCT00976989)
Timeframe: From baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)
| Intervention | percentage of participants (Number) |
|---|
| Neoadjuvant Period (n=72, 75, 76) | Adjuvant Period (n= 66, 64, 63) | Follow-up Period (n=21, 18, 23) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 5.6 | 3.0 | 0 |
,| T+P Concomitant Non-Anthracycline Chemotherapy | 2.6 | 4.8 | 4.3 |
,| T+P Sequential Anthracycline-based Chemotherapy | 4.0 | 0 | 11.1 |
Safety: Percentage of Participants With Cardiac Symptoms Associated With Symptomatic Left Ventricular Systolic Dysfunction (LVSD)
Percentage of participants with signs or symptoms of cardiac events. (NCT00976989)
Timeframe: From Baseline to end of Neoadjuvant Period (up to 18 weeks), Adjuvant Period (up to 1.5 years), Follow-up Period (up to 3.5 years)
| Intervention | percentage of participants (Number) |
|---|
| Neoadjuvant Period (n=72, 75, 76) | Adjuvant Period (n= 68, 65, 67) | Follow-up Period (n=70, 75, 74) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 1.4 | 0 | 0 |
,| T+P Concomitant Non-Anthracycline Chemotherapy | 0 | 1.5 | 0 |
,| T+P Sequential Anthracycline-based Chemotherapy | 2.7 | 0 | 1.3 |
Efficacy: Clinical Response Rate
Tumor response is defined as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD) and is identified as per local practice. Clinical response rate is defined as the percentage of participants who achieve a response of CR or PR at any time pre-surgery. Per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by mammogram or magnetic resonance imaging (MRI) and clinical breast examination (CBE), CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions. (NCT00976989)
Timeframe: During each 3-week cycle of 6 total cycles: up to 18 weeks
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 91.8 |
| T+P Sequential Anthracycline-based Chemotherapy | 94.7 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 89.6 |
Efficacy: Percentage of Participants Achieving Breast Conserving Surgery
This is the percentage of participants who achieved breast conserving surgery out of the intent-to-treat population without inflammatory breast cancer, as these participants received mastectomy irrespective of their response to neoadjuvant (pre-operative) treatment. (NCT00976989)
Timeframe: At approximately 18 weeks
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 21.7 |
| T+P Sequential Anthracycline-based Chemotherapy | 16.7 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 27.0 |
Efficacy: Percentage of Participants With Complete Pathological Response (pCR)
pCR is defined as the absence of invasive neoplastic cells at microscopic examination of the tumor remnants after surgery following primary systemic therapy. pCR is evaluated after 6 cycles of treatment and surgery or following withdrawal from the study whichever occurs sooner. (NCT00976989)
Timeframe: At surgery, after 18 weeks (6 cycles) of treatment
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 61.6 |
| T+P Sequential Anthracycline-based Chemotherapy | 57.3 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 66.2 |
Efficacy: Percentage of Participants Without a Disease-Free Survival (DFS) Event
The DFS was defined as the time from the first date of no disease (i.e., date of surgery) to the first documentation of progressive disease (PD) or death. PD was assessed using RECIST v1.0 and MRI and CBE. It 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 the appearance of one or more new lesions. Any evidence of contralateral disease in situ was not considered as PD. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be disease-free. (NCT00976989)
Timeframe: From baseline to end of study up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 85.5 |
| T+P Sequential Anthracycline-based Chemotherapy | 88.1 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 84.7 |
Efficacy: Percentage of Participants Without a Progression-Free Survival (PFS) Event
Progression-free survival was defined as the time from the date of randomization to the first documentation of PD or death from any cause, whichever occurred first. PD was assessed using RECIST v1.0 and MRI and CBE. It 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 the appearance of one or more new lesions. Participants who were withdrawn from the study without documented PD were censored at the date of the last assessment when the participant was known to be free from PD. Participants without post-baseline assessments but known to be alive were censored at the time of randomization plus one day. (NCT00976989)
Timeframe: From baseline to end of study up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 86.3 |
| T+P Sequential Anthracycline-based Chemotherapy | 85.3 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 81.8 |
Efficacy: Percentage of Participants Without an Overall Survival (OS) Event
Overall survival (OS) was defined as the time from randomization to the date of death from any cause. Participants who were alive or lost to follow-up were censored at the last known alive date. Participants with no post-baseline information were censored at the date of randomization plus one day. (NCT00976989)
Timeframe: From baseline to end of study up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 93.2 |
| T+P Sequential Anthracycline-based Chemotherapy | 90.7 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 87.0 |
Efficacy: Time to Clinical Response
Time to clinical response is defined as the time from the date of first dose received to the first date of assessment of clinical response. Clinical response is defined as a response of CR or PR at any time pre-surgery. Per RECIST v1.0 for target lesions and assessed by mammogram or MRI and CBE, CR is disappearance of all target lesions; PR is >=30% decrease in the sum of the longest diameter of target lesions. (NCT00976989)
Timeframe: Up to 18 weeks
| Intervention | weeks (Median) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 3.6 |
| T+P Sequential Anthracycline-based Chemotherapy | 6.3 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 4.9 |
Safety: Maximum Decrease in Left Ventricular Ejection Fraction (LVEF) Measures
Maximum decrease in LVEF measures is the change from baseline at worst treatment value. LVEF is measured as percentage. (NCT00976989)
Timeframe: From baseline up to approximately 3.5 years
| Intervention | percentage (ejection fraction) (Mean) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | -6.6 |
| T+P Sequential Anthracycline-based Chemotherapy | -8.4 |
| T+P Concomitant Non-Anthracycline Chemotherapy | -7.0 |
Safety: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Decline During Pre-operative (Neoadjuvant) Period
Percentage of participants with LVEF measures decline of ≥ 10% from baseline and to a value of <50% during the pre-operative (neoadjuvant) period. (NCT00976989)
Timeframe: From baseline up to approximately 18 weeks
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 5.6 |
| T+P Sequential Anthracycline-based Chemotherapy | 5.3 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 3.9 |
Safety: Percentage of Participants With Symptomatic Cardiac Events as Assessed by the Investigator
Left ventricular systolic dysfunction (LVSD) as assessed by the Investigator, including Grade 3, 4 or 5 symptomatic LVSD with symptomatic cardiac events. (NCT00976989)
Timeframe: From baseline up to approximately 3.5 years
| Intervention | percentage of participants (Number) |
|---|
| T+P Concomitant Anthracycline-based Chemotherapy | 0 |
| T+P Sequential Anthracycline-based Chemotherapy | 2.7 |
| T+P Concomitant Non-Anthracycline Chemotherapy | 1.3 |
Time to Onset of Secondary Primary Malignancies
Time of Onset of Secondary Primary Malignancies was considered an event of interest (NCT00988208)
Timeframe: The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days
| Intervention | months (Median) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 29.7 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 19.7 |
Progression-Free Survival (PFS)
PFS was the time from randomization to disease progression, or death, whatever occurred first. Progression criteria was met by analysis of target and non-target lesions as defined by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria. 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 of the diameters while on study or the appearance of one or more new lesions; an increase of at least 5mm as a total sum. Lymph nodes identified as target lesions (≥ 15 mm diameter in short axis) will be followed and reported by changes in diameter of short axis; or the unequivocal progression of a non-target lesion defined as an increase in the overall disease burden based on the change in non-measurable disease that is comparable in scope to the increase required to declare PD for measurable disease; Two or more new bone lesions as detected by bone scan (NCT00988208)
Timeframe: From randomization until disease progression or death from any cause; up to the cut-off date of 13 Jan 2012; maximum time on study was approximately 26 months
| Intervention | Weeks (Median) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 46 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 45 |
Percentage of Participants With an Objective Response According to Response Evaluation Criteria in Solid Tumors - RECIST Version 1.1 Criteria
Objective response (OR) is defined as having complete response (CR) or partial response (PR) as best overall response based on RECIST Criteria 1.1 and defines a CR = Disappearance of all target lesions except lymph nodes (LN); LN must have a decrease in the short axis to <10mm; PR = 30% decrease in sum of diameters of target lesions taking as reference the baseline sum diameters; Progressed Disease (PD) = 20% increase in sum of diameters of target lesions taking as a reference the smallest sum of diameters and an absolute increase of ≥5 mm; the appearance of ≥1 new lesions; Stable Disease (SD)= Neither shrinkage to qualify for PR nor increase to qualify for PD taking the smallest sum diameters on study as reference. For non-target lesions a CR = Disappearance of all non-target lesions and all LN must be non-pathological in size <10 mm; Non-CR/Non PD: persistence of one or more non-target lesions; PD = unequivocal progression of existing non-target lesions or appearance of new ones (NCT00988208)
Timeframe: From day 1 to data cut-off 13 January 2012; maximum time on study was approximately 26 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 24.3 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 22.1 |
Percentage of Participants Who Received Post-Study Therapies
Percentage of Participants Who Received Post-Study Therapies for advanced Prostate Cancer. (NCT00988208)
Timeframe: The date when the first consent form was signed to the last date of AE data collection;up to 5 years; up to the date of the final data analysis date of 20 April 2017
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | 70.8 |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 69.0 |
Overall Survival (OS)
Overall survival (OS) was the time from the date of randomization to the date of death from any cause. If no death was reported for a participant before the cut-off date for OS analysis, OS was censored at the last date at which the participant was alive. The median OS was calculated based on Kaplan-Meier estimates and corresponding 95% confidence interval (CI) was calculated using the method provided by Brookmeyer and Crowley. (NCT00988208)
Timeframe: From randomization until death from any cause up to the cut-off date of 13 January 2012; up to approximately 26 months
| Intervention | weeks (Median) |
|---|
| Docetaxel/Prednisone/Placebo (DP) | NA |
| Docetaxel/Prednisone/Lenalidomide (DPL) | 77 |
Number of Participants With Treatment Emergent Adverse Events (AEs)
A TEAE is defined as any AE occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. A TESAE is defined as any serious adverse event (SAE) occurring or worsening on or after the first dose of study drug and within 28 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; (NCT00988208)
Timeframe: From the time from of first dose of study drug administration to 28 days after the last dose of study drug and up to the data cut off date of 13 January 2012; the maximum duration of study drug was 93 weeks for DP and 90.6 weeks for DPL
| Intervention | participants (Number) |
|---|
| Any TEAE | Any TEAE related to lenalidomide or placebo | Any TEAE related to docetaxel/prednisone | Any severity grade 3-4 TEAE | Any serious AE (SAE) | Any SAE related to lenalidomide or placebo | Any SAE related to docetaxel/prednisone | Any AE causing discontinuation of lenalidomide/PBO | Any AE causing withdrawal of docetaxel/prednisone | Any TEAE leading to death |
|---|
| Docetaxel/Prednisone/Lenalidomide (DPL) | 517 | 412 | 481 | 381 | 279 | 167 | 182 | 150 | 169 | 24 |
,| Docetaxel/Prednisone/Placebo (DP) | 512 | 379 | 475 | 303 | 171 | 62 | 86 | 82 | 127 | 16 |
Percentage of Participants With Secondary Primary Malignancies During the Course of the Trial
Second primary malignancies were monitored as events of interest and reported as serious adverse events throughout the course of the trial. (NCT00988208)
Timeframe: The date when the first consent form was signed to the last date of AE data collection; up to the date of the final data analysis date of 30 November 2016; 7 years and 19 days
| Intervention | percentage of participants (Number) |
|---|
| Invasive Secondary Primary Malignancies | Non-invasive Secondary Primary Malignancies |
|---|
| Docetaxel/Prednisone/Lenalidomide (DPL) | 1.7 | 1.0 |
,| Docetaxel/Prednisone/Placebo (DP) | 1.3 | 0.4 |
Response Rates Confirmed With CT or MRI
"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.~During treatment, a limited history, physical examination, assessment of toxicity, CBC with differentials, and blood chemistry tests were repeated weekly. A chest X-ray was performed every 2 weeks before each cycle. Appropriate imaging studies, including CT scans of the chest and upper abdomen, were performed every two cycles to assess the treatment response, and sooner, if required, to document disease progression. Objective tumor responses were assessed according to the RECIST criteria V 1.0." (NCT00995761)
Timeframe: after every 2 cycles of docetaxel and cisplatin
| Intervention | percentage of participants (Number) |
|---|
| Biweekly Schedule of Docetaxel and Cisplatin | 64.6 |
Progression-free Survival
"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 followup were censored on the date of last CT Scan.~Assessed with a log-rank test stratified by whether the patient had whole pelvic radiotherapy prior to starting the study treatment. The product-limit method will be used to estimate the cumulative distribution of PFS for the patients assigned to each treatment group." (NCT01012297)
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 60 months
| Intervention | months (Median) |
|---|
| Arm I Gem+Doce+Placebo | 6.2 |
| Arm II Gem+Doce+Bev | 4.2 |
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 followup were censored on the date of last CT Scan.~The product-limit method will be used to estimate the cumulative distribution of overall survival times for the patients assigned to each treatment group." (NCT01012297)
Timeframe: Up to 5 years
| Intervention | months (Median) |
|---|
| Arm I Gem+Doce+Placebo | 26.9 |
| Arm II Gem+Doce+Bev | 23.3 |
Objective Response Rate as Measured by RECIST 1.1 Criteria
"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." (NCT01012297)
Timeframe: Up to 5 years
| Intervention | percentage of participants (Number) |
|---|
| Arm I Gem+Doce+Placebo | 31.5 |
| Arm II Gem+Doce+Bev | 35.8 |
Frequency and Severity of Adverse Effects as Assessed by the CTCAE Version 4.0
"Count of participants with Adverse events (AEs) that are CTCAE Grade 3 or worse.~Please refer to the adverse event reporting for more detail." (NCT01012297)
Timeframe: Up to 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm I Gem+Doce+Placebo | 36 |
| Arm II Gem+Doce+Bev | 46 |
Disease Control (CR + PR + Stable Disease [SD])
Complete Response (CR) + Partial Response (PR) + Stable disease (NCT01064479)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 47 |
| Arm B (Combination Chemotherapy and Placebo) | 41 |
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
| Intervention | months (Median) |
|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 16.95 |
| Arm B (Combination Chemotherapy and Placebo) | 13.67 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Progressive Disease | Stable Disease | Inevaluable |
|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 4 | 27 | 8 | 16 | 5 |
,| Arm B (Combination Chemotherapy and Placebo) | 5 | 19 | 13 | 17 | 5 |
Rash Rates
Participants with a Rash of at least grade 2 within cycle 1. (NCT01064479)
Timeframe: 5 years
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 20 |
| Arm B (Combination Chemotherapy and Placebo) | 4 |
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
| Intervention | months (Median) |
|---|
| Arm A (Combination Chemotherapy and Erlotinib Hydrochloride) | 6.08 |
| Arm B (Combination Chemotherapy and Placebo) | 4.4 |
Number of Participants Progression Free at 1 Year
Participants prostatic specific antigen (PSA) progression-free or event-free survival (that is, freedom from treatment failure) 1 year postoperatively. Treatment failure defined as objective tumor progression during therapy or in year after surgery, confirmed postoperative PSA ⩾1 ngml - 1, or any postoperative radiation, hormonal or other systemic therapy. Participants who did not undergo surgery within 8 weeks of completing 1 year of therapy on protocol (for any reason, including participant refusal) were counted as treatment failure, as were participants whose surgery was begun and aborted. (NCT01076335)
Timeframe: 1 Year
| Intervention | participants (Number) |
|---|
| Neoadjuvant Hormones + Docetaxel | 13 |
Phase 2: Cmax: Maximum Observed Plasma Concentration for Docetaxel
(NCT01084655)
Timeframe: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) |
|---|
| Phase 2 Cycle 1: Docetaxel 75 mg/m^2 + Prednisone 5 mg | 1330 |
| Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 1600 |
Phase 2: Best PSA Response
Best PSA response was defined as the maximum PSA percent reduction from baseline at any time beyond Cycle 1. (NCT01084655)
Timeframe: Cycle 2 Day 1 up to Cycle 12 Day 21
| Intervention | percent change (Mean) |
|---|
| Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone | -61.72 |
Phase 2: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel
(NCT01084655)
Timeframe: Cycle 1 Day 1: pre-dose and at multiple time points (up to 24 hours) post-end of docetaxel infusion; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-end of docetaxel infusion
| Intervention | nanogram*hour per milliliter (ng*hr/mL) (Geometric Mean) |
|---|
| Phase 2 Cycle 1: Docetaxel 75 mg/m^2 + Prednisone 5 mg | 1180 |
| Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 1270 |
Phase 2: AUC 0-tau: Area Under the Plasma Concentration Versus Time Curve Zero to the Time of the End of the Dosing Interval for Orteronel
(NCT01084655)
Timeframe: Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Phase 2 Cycle 1: Orteronel 400 mg BID + Docetaxel + Prednisone | 18000 |
| Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 871 |
Phase 2: Time to PSA Progression
Time to PSA progression was defined as (date of PSA progression) - (date of first dose of drug) + 1, where PSA progression was defined as: For participants whose PSA concentrations never declined before the end of Cycle 4 of treatment: a) >=25% increase over the baseline level and an increase in absolute PSA concentration >=2 ng/mL; For participants who initially experienced a PSA decline: a) >=25% increase in PSA above the nadir concentration and an increase in absolute PSA concentration >=2 ng/mL. (NCT01084655)
Timeframe: Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)
| Intervention | days (Median) |
|---|
| Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 203 |
Phase 2: Time to Radiographic Disease Progression
Time to Radiographic Disease Progression was defined as (date of Radiographic Disease progression) - (date of first dose of drug) + 1. Radiographic disease progression is defined as the presence of progressive disease (PD) according to Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1) criteria and/or bone scan progression determined according to second Prostate Cancer Clinical Trials Working Group (PCWG2) bone scan criteria. (NCT01084655)
Timeframe: Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)
| Intervention | days (Median) |
|---|
| Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 393 |
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) or Serious Adverse Events (SAE)
(NCT01084655)
Timeframe: Baseline up to 30 days after last dose of study drug (Day of last dose for Phase 1: Cycle 84 Day 21; Phase 2: Cycle 48 Day 21)
| Intervention | participants (Number) |
|---|
| TEAE | SAE |
|---|
| Phase 1: Orteronel 200 mg BID + Docetaxel + Prednisone | 6 | 5 |
,| Phase 1: Orteronel 400 mg BID + Docetaxel + Prednisone | 8 | 5 |
,| Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 23 | 16 |
Phase 2: Percentage of Participants With Objective Measurable Disease Response
Percentage of participants with objective measurable disease response based assessment of complete response (CR), partial response (PR), stable disease or PD according to RECIST (Version 1.1). A CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to less than (<)10 millimeter (mm). A PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of longest diameters of non-lymph node lesions and of the short diameter(s) or short axis of lymph nodes. (NCT01084655)
Timeframe: Baseline until disease progression or death, whichever occurred first (up to approximately 25.4 months)
| Intervention | percentage of participants (Number) |
|---|
| Complete response | Partial response | Stable Disease | Progressive Disease |
|---|
| Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 0 | 70 | 30 | 0 |
Phase 2: Change From Baseline in Circulating Tumor Cells (CTCs)
Baseline is defined as the last scheduled observed measurement prior to the first dose of drug. (NCT01084655)
Timeframe: Cycle 2 Day 1, Cycle 5 Day 1, Cycle 9 Day 1, Cycle 13 Day 1, Cycle 17 Day 1, Cycle 21 Day 1, End of treatment (approximately up to Cycle 48), Last assessment (30 days after last dose of study drug, approximately up to 1038 days)
| Intervention | milliliter (mL) (Mean) |
|---|
| Baseline (n=21) | Change at Cycle 2 Day 1 (n=12) | Change at Cycle 5 Day 1 (n=16) | Change at Cycle 9 Day 1 (n=6) | Change at Cycle 13 Day 1 (n=7) | Change at Cycle 17 Day 1 (n=5) | Change at Cycle 21 Day 1 (n=1) | Change at End of treatment (n=11) | Change at Last assessment (n=18) |
|---|
| Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 47.9 | -11.9 | -39.0 | -25.5 | -11.3 | -18.8 | -5.0 | -40.2 | -35.0 |
Phase 2: Percentage of Participants With Prostate-specific Antigen (PSA) Response of 30 Percent (%), 50%, and 90%
PSA response rates (PSA-30, PSA-50, and PSA-90) were defined as greater than or equal to (>=) 30%, 50%, and 90% reductions, respectively, from baseline in PSA concentration. (NCT01084655)
Timeframe: Cycle 4 Day 21
| Intervention | percentage of participants (Number) |
|---|
| PSA-30 | PSA-50 | PSA-90 |
|---|
| Phase 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 68 | 59 | 23 |
Phase 2: Cmax, ss: Maximum Observed Plasma Concentration at Steady State for Orteronel
(NCT01084655)
Timeframe: Cycle 1 Day 21: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel; Cycle 2 Day 1: pre-dose and at multiple time points (up to 8 hours) post-dose for orteronel
| Intervention | ng/mL (Geometric Mean) |
|---|
| Phase 2 Cycle 1: Orteronel 400 mg BID + Docetaxel + Prednisone | 2660 |
| Phase 2 Cycle 2: Orteronel 400 mg BID + Docetaxel + Prednisone | 3000 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 44
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 44 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.3320 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 46
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 46 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.3320 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 5
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 5 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -0.1164 |
| Bevacizumab 15 mg/kg Q3W | 0.2280 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 6
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 6 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0474 |
| Bevacizumab 15 mg/kg Q3W | -0.0735 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 7
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 7 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -0.0331 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 8
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 8 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0627 |
| Bevacizumab 15 mg/kg Q3W | -0.0523 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 9
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 9 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -0.1904 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at End of Study
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, end of study (4-6 weeks after the last bevacizumab infusion) (maximum up to 5 years and 9 months)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -0.1344 |
| Bevacizumab 15 mg/kg Q3W | -0.1178 |
Change From Baseline in EQ-5D-VAS Score at Cycle 10
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 10 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 6.0 |
| Bevacizumab 15 mg/kg Q3W | 14.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 11
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 11 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 2.0 |
| Bevacizumab 15 mg/kg Q3W | 40.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 12
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 12 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 13.7 |
| Bevacizumab 15 mg/kg Q3W | 60.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 13
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 13 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -3.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 14
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 14 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -5.0 |
| Bevacizumab 15 mg/kg Q3W | 9.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 15
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 15 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 5.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 16
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 16 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 7.3 |
Change From Baseline in EQ-5D-VAS Score at Cycle 17
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 17 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 30.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 20
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 20 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 15.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 21
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 21 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 27.5 |
| Bevacizumab 15 mg/kg Q3W | 8.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 22
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 22 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 52.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 23
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 23 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 23.5 |
| Bevacizumab 15 mg/kg Q3W | 10.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 24
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 24 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -20.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 25
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 25 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 9.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 26
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 26 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -20.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 27
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 27 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -20.0 |
| Bevacizumab 15 mg/kg Q3W | 10.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 28
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 28 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 9.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 29
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 29 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -20.0 |
| Bevacizumab 15 mg/kg Q3W | 10.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 3
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 3 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 20.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 30
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 30 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -20.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 32
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 32 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 9.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 36
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 36 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 8.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 37
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 37 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 8.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 39
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 39 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 8.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 4
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 4 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -1.9 |
| Bevacizumab 15 mg/kg Q3W | 3.3 |
Change From Baseline in EQ-5D-VAS Score at Cycle 40
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 40 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 5.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 42
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 42 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 7.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 44
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 44 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 13.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 46
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 46 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 14.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 5
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 5 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -8.2 |
| Bevacizumab 15 mg/kg Q3W | 7.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 6
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 6 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 9.8 |
| Bevacizumab 15 mg/kg Q3W | 21.4 |
Change From Baseline in EQ-5D-VAS Score at Cycle 7
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 7 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -3.6 |
| Bevacizumab 15 mg/kg Q3W | -9.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 8
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 8 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 11.0 |
| Bevacizumab 15 mg/kg Q3W | 35.0 |
Change From Baseline in EQ-5D-VAS Score at Cycle 9
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 9 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -5.8 |
| Bevacizumab 15 mg/kg Q3W | 27.5 |
Change From Baseline in EQ-5D-VAS Score at End of Study
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, end of study (4-6 weeks after the last bevacizumab infusion) (maximum up to 5 years and 9 months)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -2.7 |
| Bevacizumab 15 mg/kg Q3W | -1.4 |
Change From Baseline in FACT-B Score at Cycle 10
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 10 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 2.71 |
| Bevacizumab 15 mg/kg Q3W | 4.61 |
Change From Baseline in FACT-B Score at Cycle 11
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 11 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 6.67 |
| Bevacizumab 15 mg/kg Q3W | 8.17 |
Change From Baseline in FACT-B Score at Cycle 12
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 12 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 9.22 |
| Bevacizumab 15 mg/kg Q3W | 21.89 |
Change From Baseline in FACT-B Score at Cycle 13
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 13 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -8.00 |
Change From Baseline in FACT-B Score at Cycle 14
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 14 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 6.83 |
| Bevacizumab 15 mg/kg Q3W | 2.33 |
Change From Baseline in FACT-B Score at Cycle 15
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 15 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -6.67 |
Change From Baseline in FACT-B Score at Cycle 16
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 16 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 11.83 |
Change From Baseline in FACT-B Score at Cycle 17
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 17 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 22.63 |
Change From Baseline in FACT-B Score at Cycle 18
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 18 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 10.28 |
| Bevacizumab 15 mg/kg Q3W | 5.33 |
Change From Baseline in FACT-B Score at Cycle 20
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 20 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 20.06 |
Change From Baseline in FACT-B Score at Cycle 21
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 21 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 25.75 |
| Bevacizumab 15 mg/kg Q3W | 10.33 |
Change From Baseline in FACT-B Score at Cycle 22
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 22 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 13.67 |
Change From Baseline in FACT-B Score at Cycle 23
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 23 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 9.67 |
| Bevacizumab 15 mg/kg Q3W | 7.33 |
Change From Baseline in FACT-B Score at Cycle 24
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 24 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 6.00 |
Change From Baseline in FACT-B Score at Cycle 25
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 25 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 11.33 |
Change From Baseline in FACT-B Score at Cycle 26
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 26 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 3.22 |
Change From Baseline in FACT-B Score at Cycle 27
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 27 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -26.78 |
| Bevacizumab 15 mg/kg Q3W | 12.33 |
Change From Baseline in FACT-B Score at Cycle 28
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 28 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 16.33 |
Change From Baseline in FACT-B Score at Cycle 29
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 29 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -3.00 |
| Bevacizumab 15 mg/kg Q3W | 9.78 |
Change From Baseline in FACT-B Score at Cycle 3
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 3 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 14.56 |
Change From Baseline in FACT-B Score at Cycle 30
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 30 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -3.11 |
Change From Baseline in FACT-B Score at Cycle 32
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 32 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 10.33 |
Change From Baseline in FACT-B Score at Cycle 36
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 36 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 3.33 |
Change From Baseline in FACT-B Score at Cycle 37
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 37 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 5.33 |
Change From Baseline in FACT-B Score at Cycle 39
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 39 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 9.33 |
Change From Baseline in FACT-B Score at Cycle 4
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 4 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 1.29 |
| Bevacizumab 15 mg/kg Q3W | 0.09 |
Change From Baseline in FACT-B Score at Cycle 42
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 42 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 10.33 |
Change From Baseline in FACT-B Score at Cycle 44
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 44 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 11.33 |
Change From Baseline in FACT-B Score at Cycle 46
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 46 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 13.33 |
Change From Baseline in FACT-B Score at Cycle 5
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 5 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -10.77 |
| Bevacizumab 15 mg/kg Q3W | 4.50 |
Change From Baseline in FACT-B Score at Cycle 6
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 6 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 9.47 |
| Bevacizumab 15 mg/kg Q3W | 10.08 |
Change From Baseline in FACT-B Score at Cycle 7
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 7 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -6.24 |
| Bevacizumab 15 mg/kg Q3W | 1.83 |
Change From Baseline in FACT-B Score at Cycle 8
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 8 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 15.01 |
| Bevacizumab 15 mg/kg Q3W | 15.44 |
Change From Baseline in FACT-B Score At Cycle 9
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 9 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -2.43 |
| Bevacizumab 15 mg/kg Q3W | 7.00 |
Change From Baseline in FACT-B Score at End of Study
FACT-B is used for assessment of health-related QoL in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, end of study (4-6 weeks after the last bevacizumab infusion) (maximum up to 5 years and 9 months)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -10.33 |
| Bevacizumab 15 mg/kg Q3W | -1.01 |
Overall Survival
Overall survival was defined as the time from start of taxane plus bevacizumab therapy to death due to any cause. Overall survival was calculated in months as (date of death from any cause - date of first administration of taxane or bevacizumab + 1) / 30.4375 and rounded to 1 decimal place. Participants for whom no death was captured on the clinical database were censored at the last date they were known to be alive. (NCT01094184)
Timeframe: Baseline up to death (overall approximately 5 years and 9 months)
| Intervention | months (Median) |
|---|
| Bevacizumab 10 mg/kg Q2W | 11.6 |
| Bevacizumab 15 mg/kg Q3W | 18.9 |
Percentage of Participants Who Died Due to Any Cause
(NCT01094184)
Timeframe: Baseline up to death (overall approximately 5 years and 9 months)
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab 10 mg/kg Q2W | 97.1 |
| Bevacizumab 15 mg/kg Q3W | 84.6 |
Percentage of Participants With Disease Progression
Disease progression was defined as greater than or equal to (>/=) 20 percent (%) relative increase and >/=5 mm of absolute increase in the sum of diameters (SD) of target lesions (TLs), taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. (NCT01094184)
Timeframe: Baseline up to disease progression (overall approximately 5 years and 9 months)
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab 10 mg/kg Q2W | 74.3 |
| Bevacizumab 15 mg/kg Q3W | 69.2 |
Time to Disease Progression
Time to disease progression was defined as the time from the start of taxane plus bevacizumab therapy to investigator assessed disease progression and was calculated in months as (date of Investigator assessed disease progression - date of first administration of taxane or bevacizumab + 1) / 30.4375 and rounded to 1 decimal place. Participants who had not progressed at the time of study completion (including participants who had died before progressive disease) or who were lost to follow-up were censored at the last bevacizumab administration date. Disease progression was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, or appearance of 1 or more new lesions. (NCT01094184)
Timeframe: Baseline up to disease progression (overall approximately 5 years and 9 months)
| Intervention | months (Median) |
|---|
| Bevacizumab 10 mg/kg Q2W | 6.7 |
| Bevacizumab 15 mg/kg Q3W | 7.9 |
Change From Baseline in EQ-5D - Visual Analogue Scale (VAS) Score at Cycle 2
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 2 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Baseline | Change at Cycle 2 |
|---|
| Bevacizumab 10 mg/kg Q2W | 64.8 | -1.0 |
,| Bevacizumab 15 mg/kg Q3W | 60.3 | -8.3 |
Change From Baseline in Euro Quality of Life (EQ-5D) - Health State Questionnaire Score at Cycle 2
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 2 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change at Cycle 2 |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.6391 | 0.1090 |
,| Bevacizumab 15 mg/kg Q3W | 0.8152 | -0.2074 |
Change From Baseline in Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Score at Cycle 2
FACT-B is used for assessment of health-related quality of life (QoL) in participants with breast cancer. It consists of 36 items, summarized to 5 subscales: physical (7 items), functional (7 items), social/family (7 items); all 3 ranged from 0 to 28, emotional (6 items) ranging from 0 to 24, and breast cancer subscale (9 items) ranging from 0 to 36; high subscale score represents a better QoL. All single-item measures range from 0='Not at all' to 4='Very much'. Total possible score ranged from 0 to 144. High scale score represents a better QoL. (NCT01094184)
Timeframe: Baseline, Cycle 2 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change at Cycle 2 |
|---|
| Bevacizumab 10 mg/kg Q2W | 98.3 | 5.83 |
,| Bevacizumab 15 mg/kg Q3W | 102.21 | -2.48 |
Change From Baseline in EQ-5D-VAS Score at Cycle 18
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 18 (Cycle length=2 and 3 weeks)
| Intervention | mm (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 9.5 |
| Bevacizumab 15 mg/kg Q3W | 10.0 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 10
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 10 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0253 |
| Bevacizumab 15 mg/kg Q3W | -0.0540 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 11
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 11 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0018 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 12
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 12 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0997 |
| Bevacizumab 15 mg/kg Q3W | -0.0520 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 13
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 13 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -0.0930 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 14
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 14 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0620 |
| Bevacizumab 15 mg/kg Q3W | -0.3320 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 15
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 15 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0175 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 16
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 16 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0060 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 17
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 17 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.1057 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 18
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 18 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0970 |
| Bevacizumab 15 mg/kg Q3W | -0.1570 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 20
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 20 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.1035 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 21
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 21 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.2955 |
| Bevacizumab 15 mg/kg Q3W | -0.1570 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 22
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 22 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0710 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 23
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 23 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0625 |
| Bevacizumab 15 mg/kg Q3W | -0.2280 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 24
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 24 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0540 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 25
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 25 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.3320 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 26
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 26 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0180 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 27
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 27 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0540 |
| Bevacizumab 15 mg/kg Q3W | -0.3320 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 28
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 28 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 29
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 29 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -0.0860 |
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 3
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 3 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | 0.1920 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 30
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 30 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | 0.0540 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 32
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 32 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 36
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 36 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 37
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 37 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 39
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 39 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 4
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 4 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 10 mg/kg Q2W | -0.0105 |
| Bevacizumab 15 mg/kg Q3W | -0.0906 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 40
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 40 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Change From Baseline in EQ-5D- Health State Questionnaire Score at Cycle 42
EQ-5D: participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state. Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. (NCT01094184)
Timeframe: Baseline, Cycle 42 (Cycle length=2 and 3 weeks)
| Intervention | units on a scale (Mean) |
|---|
| Bevacizumab 15 mg/kg Q3W | -0.2610 |
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. (NCT01094288)
Timeframe: From enrollment through 30 days after the last dose of study drug (approximately up to 77 months)
| Intervention | participants (Number) |
|---|
| AEs | SAEs |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 6 | 3 |
,| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 15 | 8 |
,| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 4 | 3 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 3 | 2 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 2 | 2 |
,| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 2 | 1 |
,| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 5 | 3 |
,| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 4 | 2 |
Terminal Phase Elimination Half-life (T1/2) for Docetaxel
(NCT01094288)
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
| Intervention | hr (Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 21.80 | 24.18 |
,| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 22.88 | 20.73 |
,| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 16.34 | 22.00 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 15.60 | 16.40 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 19.25 | 16.95 |
,| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 30.70 | 25.10 |
,| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 24.00 | 20.40 |
,| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 24.80 | 26.00 |
Overall Response Rate (ORR) Assessed for Overall Participant Population
ORR is defined as percentage of participants who achieved complete response (CR) or partial response (PR) as assessed by response evaluation criteria in solid tumors (RECIST) v 1.1. CR was defined as disappearance of all target and non-target 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 was defined as ≥30% decrease in sum of longest diameter (LD) of target lesions in reference to Baseline. RECIST-Evaluable Population is subset of safety population who had measurable disease by RECIST v 1.1 at baseline and had at least 1 post baseline response. prostate specific antigen (PSA)-Evaluable Population is subset of the safety population who had a baseline PSA reference value (>5 ng/mL) and at least 12 weeks post-baseline PSA assessment for participants with no decline from baseline, or PSA progression within 12 weeks of treatment for participants with PSA decline from baseline. (NCT01094288)
Timeframe: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
| Intervention | percentage of participants (Number) |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 50 |
| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 10 |
| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 100 |
| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 50 |
| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 0 |
| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 25 |
| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 0 |
| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 50 |
AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration for Docetaxel
(NCT01094288)
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
| Intervention | hr*ng/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 2328.3 | 1750.8 |
,| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 1925.7 | 2416.4 |
,| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 1593.1 | 1596.0 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 2163.4 | 7811.5 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 2394.6 | 2895.7 |
,| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 1830.0 | 1622.8 |
,| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 1750.1 | 25.5 |
,| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 1579.8 | 2510.0 |
AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity for Docetaxel
(NCT01094288)
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
| Intervention | hr*ng/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 2653.3 | 1918.0 |
,| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 2240.6 | 2632.2 |
,| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 1734.7 | 1631.0 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 3570.0 | 4000.0 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 2600.0 | 3099.0 |
,| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 2130.0 | 1785.4 |
,| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 2007.3 | 2019.8 |
,| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 1730.9 | 3120.0 |
AUCτ: Area Under the Plasma Concentration-time Curve From Time 0 to Day 7 Over the Dosing Interval for Alisertib
(NCT01094288)
Timeframe: Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1
| Intervention | hr*nmol/L (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 5/Day 7 |
|---|
| Alisertib 10 mg | 1635.0 | 3052.8 |
,| Alisertib 20 mg | 3303.0 | 8546.0 |
,| Alisertib 30 mg | 4387.5 | 13199.1 |
,| Alisertib 40 mg | 8013.7 | 12630.0 |
Overall Response Rate for Prostate Cancer Participants
ORR is defined as percentage of participants who achieved CR or PR as assessed by either RECIST v 1.1 or PSA response by prostate cancer working group 2 (PCWG2) criteria. According to RECIST v 1.1, CR: disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR: ≥30% decrease in sum of LD of target lesions in reference to Baseline sum LD. PSA response by PCWG2 is defined as PSA at least 50% decrease in PSA value from baseline for 2 consecutive evaluations. PCWG2 defines PSA progression as the date that a 25% or greater increase and an absolute increase of 2 ng/mL or more from the nadir is documented, which is confirmed by a second value obtained 3 or more weeks later. (NCT01094288)
Timeframe: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
| Intervention | percentage of participants (Number) |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 50 |
| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 20 |
| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 100 |
| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 0 |
| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 100 |
Best Overall Response Rate Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria
Best Response Assessed by PSA Response by Prostate Cancer Working Group 2 (PCWG2) Criteria PSA response is defined as at least 50% decrease in PSA value from baseline for 2 consecutive evaluations. (NCT01094288)
Timeframe: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
| Intervention | percentage of participants (Number) |
|---|
| ≥50% Reduction from Baseline | <50% Reduction from Baseline |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 67 | 33 |
,| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 80 | 20 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 100 | 0 |
Best Overall Response Rate Assessed by RECIST Criteria
Best response rate is defined as the percentage of participants with CR, PR, CR+PR, stable disease (SD) and progressive disease (PD) as assessed by RECIST criteria 1.1 for target lesions and assessed by CT, PET or MRI. 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). (NCT01094288)
Timeframe: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
| Intervention | percentage of participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | CR+PR | Stable Disease (SD) | Progressive Disease (PD) |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 0 | 50 | 50 | 50 | 0 |
,| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 0 | 11 | 11 | 67 | 22 |
,| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 0 | 25 | 25 | 0 | 75 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 0 | 50 | 50 | 0 | 50 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 0 | 0 | 0 | 0 | 100 |
,| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 0 | 0 | 0 | 50 | 50 |
,| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 100 | 0 | 100 | 0 | 0 |
,| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 0 | 50 | 50 | 50 | 0 |
Cmax: Maximum Observed Plasma Concentration for Alisertib
(NCT01094288)
Timeframe: Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1
| Intervention | nmol/L (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 5/Day 7 |
|---|
| Alisertib 10 mg | 290.4 | 435.8 |
,| Alisertib 20 mg | 557.5 | 1140.6 |
,| Alisertib 30 mg | 751.6 | 1637.9 |
,| Alisertib 40 mg | 1346.4 | 1766.3 |
Cmax: Maximum Observed Plasma Concentration for Docetaxel
(NCT01094288)
Timeframe: Day 1 pre-dose and at multiple time points (up to 48 hours) post-dose in Cycles 1 and 2
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 2392.7 | 1825.1 |
,| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 1730.4 | 1957.0 |
,| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 1159.9 | 1061.6 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 1717.6 | 3299.9 |
,| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 2232.9 | 2504.6 |
,| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 3751.4 | 1649.7 |
,| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 1587.0 | 2146.6 |
,| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 1386.6 | 1627.8 |
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib
(NCT01094288)
Timeframe: Prior to dosing on Day 1 and Day 5 or 7 and at multiple time points (up to 12 hours) post-dose in Cycle 1
| Intervention | hr (Median) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 5/Day 7 |
|---|
| Alisertib 10 mg | 2.050 | 3.510 |
,| Alisertib 20 mg | 4.000 | 3.030 |
,| Alisertib 30 mg | 3.560 | 2.030 |
,| Alisertib 40 mg | 1.500 | 1.975 |
Duration of Stable Disease (SD)
Duration of SD is defined as the time from first dose to first PD, or censored at last SD or better. (NCT01094288)
Timeframe: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
| Intervention | days (Median) |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 253 |
| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | NA |
| Alisertib 30 mg (7D) + Docetaxel 60 mg/m^2 | 309 |
| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | 134 |
Duration of Response
Duration of response is defined as the time from the date of first documentation of a response to the date of first documented progressive disease (PD), or censored at last SD or better. (NCT01094288)
Timeframe: Baseline up to Cycle 36 (21-day cycles) until disease progression, death or EOT (approximately up to 24.8 months)
| Intervention | days (Median) |
|---|
| Alisertib 10 mg (7D) + Docetaxel 75 mg/m^2 | 187 |
| Alisertib 20 mg (7D) + Docetaxel 75 mg/m^2 | 342 |
| Alisertib 30 mg (7D) + Docetaxel 75 mg/m^2 | 830 |
| Alisertib 30 mg (5D) + Docetaxel 75 mg/m^2 | 176 |
| Alisertib 30 mg (5D) + Docetaxel 60 mg/m^2 | 79 |
| Alisertib 40 mg (5D) + Docetaxel 75 mg/m^2 + GCSF | NA |
Number of Subjects With Treatment-Emergent Adverse Events (TEAE), Treatment-Emergent Serious Adverse Events (TESAE) With a CTCAE Grade of 3 or 4
Treatment-emergent adverse event (TEAEs) were defined as events that occur following the first injection of study treatment, or that started prior to the first injection and worsened during treatment. An adverse event (AE) was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An 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 in patient hospitalization; lifethreatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent adverse events were defined as adverse events/serious adverse events that started or worsened after the study drug treatment. (NCT01106352)
Timeframe: From start of study treatment to 6 weeks after study treatment (that is maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort) and 8 weeks for serious AEs
| Intervention | Participants (Number) |
|---|
| TEAE CTCAE Grade 3 | TEAE CTCAE Grade 4 | TESAE |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 1 | 1 | 0 |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 3 | 2 | 4 |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 4 | 1 | 2 |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 6 | 10 | 7 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 3 | 6 | 4 |
Number of Subjects Who Responded to Interactive Voice Response System (IVRS) Pain
The subject completed the full BPI (short form) paper questionnaire, and clinical staff completed the analgesic log. The test consists of 10 questions addressing severity, location, chronicity, and amount of relief. In question 3, subjects with pain are asked to evaluate the severity of pain at worst in the past 24 hours in a 0 to 10 scale, with 0 indicating no pain, and 10 indicating the worst pain. (NCT01106352)
Timeframe: From start of study treatment until 12 months
| Intervention | Participants (Number) |
|---|
| Day 1 | Day 22 | Day 43 | Day 64 | Day 85 | Day 106 | Day 127 | Day 148 | Day 169 | Day 190 | Safety Follow-up | 6-Month Follow-up | 9-Month Follow-up | 12-Month Follow-up |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 23 | 24 | 22 | 21 | 20 | 20 | 19 | 18 | 17 | 17 | 18 | 1 | 12 | 7 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 11 | 11 | 10 | 10 | 11 | 9 | 6 | 5 | 5 | 5 | 9 | 2 | 7 | 5 |
Exploratory Efficacy: Weighted Mean Area Under the Curve for Bone Turnover Biomarkers
Weighted mean area under the curve for the below bone turnover biomarkers were evaluated, ICTP = pyridinoline cross-linked carboxyterminal telopeptide P1NP = N-terminal peptide of procollagen type 1 uCTX-1 = urine C-telopeptide 1 (NCT01106352)
Timeframe: From start of study treatment to 6 weeks after study treatment (maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
| Intervention | mcg/L (Mean) |
|---|
| uCTX-1 | P1NP | ICTP |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 14 | 42.9 | 4.7 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 22.6 | 106.5 | 7 |
Changes From Baseline in Weight During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
| Intervention | kilogram(s) (Mean) |
|---|
| Baseline (n= 7,3,7,33,13) | Change at Day 22 (n= 6,3,7,33,13) | Change at Day 43 (n= 6,3,7,32,13) | Change at Day 64 (n= 6,3,6,30,13) | Change at Day 85 (n= 0,0,0,28,13) | Change at Day 106 (n= 0,0,0,28,12) | Change at Day 127 (n= 0,0,0,27,8) | Change at Day 148 (n= 0,0,0,25,7) | Change at Day 169 (n= 0,0,0,25,7) | Change at Day 190 (n= 0,0,0,24,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 81.9 | -0.3 | 0.2 | 0.3 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 89.3 | -1.8 | -1 | 0.1 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 97.1 | -1.4 | -1 | -1.2 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 87.7 | -0.4 | 0 | 0.2 | -0.2 | -0.3 | -0.1 | -0.1 | -0.1 | 0.1 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 92 | -0.2 | 0.5 | 0.3 | 0.4 | 0.4 | 2.1 | 1.9 | 1.7 | -0.7 |
Changes From Baseline in Systolic and Diastolic Blood Pressure During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
| Intervention | millimeters of mercury (mmHg) (Mean) |
|---|
| SBP: Baseline (n= 7,3,7,33,13) | SBP: Change at Day 22 (n= 6,3,7,33,13) | SBP: Change at Day 43 (n= 6,3,7,32,13) | SBP: Change at Day 64 (n= 6,3,6,30,13) | SBP: Change at Day 85 (n= 0,0,0,28,13) | SBP: Change at Day 106 (n= 0,0,0,28,12) | SBP: Change at Day 127 (n= 0,0,0,27,8) | SBP: Change at Day 148 (n= 0,0,0,25,7) | SBP: Change at Day 169 (n= 0,0,0,25,7) | SBP: Change at Day 190 (n= 0,0,0,24,6) | DBP: Baseline (n= 7,3,7,33,13) | DBP: Change at Day 22 (n= 6,3,7,33,13) | DBP: Change at Day 43 (n= 6,3,7,32,13) | DBP: Change at Day 64 (n= 6,3,6,30,13) | DBP: Change at Day 85 (n= 0,0,0,28,13) | DBP: Change at Day 106 (n= 0,0,0,28,12) | DBP: Change at Day 127 (n= 0,0,0,27,8) | DBP: Change at Day 148 (n= 0,0,0,25,7) | DBP: Change at Day 169 (n= 0,0,0,25,7) | DBP: Change at Day 190 (n= 0,0,0,24,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 113 | 2.3 | -3 | -11 | NA | NA | NA | NA | NA | NA | 62 | 8 | 2.7 | -1 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 137.7 | -2.7 | -8.7 | -9.8 | NA | NA | NA | NA | NA | NA | 81.6 | -2.7 | -3.7 | -8.7 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 131.7 | -5 | -0.9 | -4.2 | NA | NA | NA | NA | NA | NA | 74.1 | 2.6 | 4.1 | -0.2 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 139.2 | -1.8 | 0.6 | -2.5 | -3.1 | -6.7 | -4.6 | -3.9 | -3.6 | -8.1 | 76.1 | 0.3 | -1.8 | -1.4 | 1.1 | -0.8 | -1.4 | -2 | -1.2 | -3.6 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 140.1 | -8.5 | -15.3 | -10.1 | -3.8 | -10.4 | -13.4 | -8.9 | -6.3 | -10 | 83 | -6.2 | -11.7 | -8.7 | -7.6 | -7.9 | -8 | -3.9 | -9 | -12 |
Changes From Baseline in Respiratory Rate During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
| Intervention | breaths/min (Mean) |
|---|
| Baseline (n= 7,3,7,33,13) | Change at Day 22 (n= 6,3,7,33,13) | Change at Day 43 (n= 6,3,7,32,13) | Change at Day 64 (n= 6,3,6,30,13) | Change at Day 85 (n= 0,0,0,28,13) | Change at Day 106 (n= 0,0,0,28,12) | Change at Day 127 (n= 0,0,0,27,8) | Change at Day 148 (n= 0,0,0,25,7) | Change at Day 169 (n= 0,0,0,25,7) | Change at Day 190 (n= 0,0,0,24,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 18.7 | -1.3 | 1.3 | 0 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 19.1 | -0.7 | -0.3 | -1 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 19.3 | -1.7 | 0 | -0.5 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 17.1 | 0.3 | 0 | 0.4 | 0 | -0.8 | 0.9 | 0.7 | -1 | 0 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 17.5 | -0.4 | 0.7 | 0.8 | -0.3 | 0.5 | 0.4 | -0.3 | 0.4 | -0.2 |
Changes From Baseline in Heart Rate During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: From start of study treatment to 6 weeks after study treatment (that is, maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
| Intervention | beats per min (Mean) |
|---|
| Baseline (n= 7,3,7,33,13) | Change at Day 22 (n= 6,3,7,33,13) | Change at Day 43 (n= 6,3,7,32,13) | Change at Day 64 (n= 6,3,6,30,13) | Change at Day 85 (n= 0,0,0,28,13) | Change at Day 106 (n= 0,0,0,28,12) | Change at Day 127 (n= 0,0,0,27,8) | Change at Day 148 (n= 0,0,0,25,7) | Change at Day 169 (n= 0,0,0,25,7) | Change at Day 190 (n= 0,0,0,24,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 58 | 9.7 | 18.3 | 13 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 88.6 | -0.2 | -4.3 | 0.7 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 80 | -0.6 | 0.9 | 6.5 | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 77.9 | 2 | 2.8 | 3.4 | 2.9 | 0.8 | 2.2 | 2.2 | 3.6 | 2.6 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 73.3 | 7.2 | 4.9 | 5.1 | 7.2 | 9.2 | 7.5 | 15.3 | 8 | 18 |
Change From Baseline in Serum Biochemistry (Platelets, Leukocytes, Lymphocytes, Neutrophils, Monocytes, Eosinophils, Basophils) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
| Intervention | giga per liter (GI/L) (Mean) |
|---|
| Platelets: Baseline (n= 7,3,7,33,13) | Platelets: Change at Day 106 (n= 1,0,0,27,11) | Platelets: Change at Day 190 (n= 0,0,0,23,6) | Leukocytes: Baseline (n= 7,3,7,33,13) | Leukocytes: Change at Day 106 (n= 1,0,0,27,11) | Leukocytes: Change at Day 190 (n= 0,0,0,23,6) | Lymphocytes: Baseline (n= 7,3,7,33,13) | Lymphocytes: Change at Day 106 (n= 1,0,0,27,11) | Lymphocytes: Change at Day 190 (n= 0,0,0,23,6) | Neutrophils: Baseline (n= 7,3,7,33,13) | Neutrophils: Change at Day 106 (n= 1,0,0,27,11) | Neutrophils: Change at Day 190 (n= 0,0,0,23,6) | Monocytes: Baseline (n= 7,3,7,33,13) | Monocytes: Change at Day 106 (n= 1,0,0,27,11) | Monocytes: Change at Day 190 (n= 0,0,0,23,6) | Eosinophils: Baseline (n= 7,3,7,33,13) | Eosinophils: Change at Day 106 (n= 1,0,0,27,11) | Eosinophils: Change at Day 190 (n= 0,0,0,23,6) | Basophils: Baseline (n= 7,3,7,33,13) | Basophils: Change at Day 106 (n= 1,0,0,27,11) | Basophils: Change at Day 190 (n= 0,0,0,23,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 196.3 | NA | NA | 5.83 | NA | NA | 1.003 | NA | NA | 4.71 | NA | NA | 0.103 | NA | NA | 0.01 | NA | NA | 0.007 | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 214.1 | 169 | NA | 9.13 | 18.7 | NA | 1.044 | 1.3 | NA | 7.809 | 517.3 | NA | 0.224 | 0.12 | NA | 0.04 | -0.12 | NA | 0.013 | 0.02 | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 266.6 | NA | NA | 8.34 | NA | NA | 0.81 | NA | NA | 7.359 | NA | NA | 0.153 | NA | NA | 0.014 | NA | NA | 0.011 | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 259.6 | -3.1 | -22 | 7.67 | -0.1 | -0.12 | 1.001 | -0.229 | -0.395 | 6.363 | 0.178 | 0.341 | 0.243 | -0.011 | -0.014 | 0.054 | -0.043 | -0.049 | 0.012 | 0.001 | -0.003 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 240.6 | 33 | 32.3 | 6.71 | 2.44 | 1.65 | 1.068 | -0.063 | -0.085 | 5.205 | 2.622 | 2.038 | 0.375 | -0.111 | -0.27 | 0.043 | -0.008 | -0.023 | 0.018 | -0.001 | -0.015 |
Change From Baseline in Serum Biochemistry (Erythrocytes) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
| Intervention | tetra per liter (TI/L) (Mean) |
|---|
| Erythrocytes: Baseline (n= 7,3,7,33,13) | Erythrocytes: Change at Day 106 (n= 1,0,0,27,11) | Erythrocytes: Change at Day 190 (n= 0,0,0,23,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 3.9 | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 3.99 | -0.4 | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 3.9 | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 3.98 | -0.25 | -0.39 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 4.02 | -0.32 | -0.15 |
Change From Baseline in Serum Biochemistry (Calcium, Chloride, Magnesium, Potassium, Phosphate, Sodium, Urea) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
| Intervention | millimole(s)/liter (Mean) |
|---|
| Calcium: Baseline (n= 7,3,7,33,13) | Calcium: Change at Day 106 (n= 1,0,0,27,11) | Calcium: Change at Day 190 (n= 0,0,0,24,6) | Chloride: Baseline (n= 7,3,7,33,13) | Chloride: Change at Day 106 (n= 1,0,0,27,11) | Chloride: Change at Day 190 (n= 0,0,0,24,6) | Magnesium: Baseline (n= 7,3,7,33,13) | Magnesium: Change at Day 106 (n= 1,0,0,27,11) | Magnesium: Change at Day 190 (n= 0,0,0,24,6) | Potassium: Baseline (n= 7,3,7,33,13) | Potassium: Change at Day 106 (n= 1,0,0,27,11) | Potassium: Change at Day 190 (n= 0,0,0,24,6) | Phosphate: Baseline (n= 7,3,7,33,13) | Phosphate: Change at Day 106 (n= 1,0,0,27,11) | Phosphate: Change at Day 190 (n= 0,0,0,24,6) | Sodium: Baseline (n= 7,3,7,33,13) | Sodium: Change at Day 106 (n= 1,0,0,27,11) | Sodium: Change at Day 190 (n= 0,0,0,24,6) | Urea: Baseline (n= 7,3,7,33,13) | Urea: Change at Day 106 (n= 1,0,0,27,11) | Urea: Change at Day 190 (n= 0,0,0,24,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 2.38 | NA | NA | 101.7 | NA | NA | 0.86 | NA | NA | 4.47 | NA | NA | 1.167 | NA | NA | 137.7 | NA | NA | 7.83 | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 2.231 | 0.2 | NA | 101.4 | -1.9 | NA | 0.93 | -4.4 | NA | 4.34 | 1.1 | NA | 1.021 | 0 | NA | 136.1 | 0 | NA | 9.14 | 1.5 | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 2.309 | NA | NA | 102 | NA | NA | 0.86 | NA | NA | 4.39 | NA | NA | 0.993 | NA | NA | 137.4 | NA | NA | 6.79 | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 2.357 | -0.065 | -0.055 | 103.2 | 0 | 0 | 0.85 | -0.02 | -0.01 | 4.29 | 0.06 | 0.04 | 1.058 | 0.086 | 0.128 | 138.5 | -0.6 | -0.5 | 7.03 | -0.26 | -0.15 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 2.307 | -0.019 | -0.143 | 101.3 | 1.5 | 2.5 | 0.84 | -0.04 | -0.06 | 4.3 | 0.11 | 0.03 | 1.145 | -0.061 | 0.203 | 137.2 | 0.8 | 2.3 | 7.78 | -0.26 | 0.7 |
Number of Subjects With Physical Examination During the Treatment Period
Any physical examination finding that was classified by the investigator as a clinically significant change (compared with previous examination) was considered an AE, documented on the eCRF, and followed until the outcome was known. The below physical examination findings were recorded and reported. GDASC = General disorders and administration site conditions MND = Metabolism and nutrition disorders SSTD= Skin and subcutaneous tissue disorders MCTD = Musculoskeletal and connective tissue disorders IPPC = Injury, poisoning and procedural complications RTMD = Respiratory, thoracic and mediastinal disorders NBMU = Neoplasms benign, malignant and unspecified (include cysts and polyps) In the below table. (NCT01106352)
Timeframe: From start of study treatment to 6 weeks after study treatment (i.e., maximum 12 weeks in dose escalation; 30 weeks in the expanded safety cohort)
| Intervention | Participants (Number) |
|---|
| At day 64: GDASC | At day 64: MND | At day 64: SSTD | At day 190: GDASC | At day 190: MCTD | At day 190: SSTD | At day 190: Vascular disorders | At day 190: Gastrointestinal disorders | At day 190: IPPC | At day 190: RTMD | At day 190: NBMU | At day 190: Social circumstances |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 2 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 5 | 0 | 2 | 7 | 1 | 7 | 0 | 1 | 2 | 0 | 2 | 1 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 2 | 1 | 6 | 2 | 0 | 2 | 1 | 1 | 0 | 1 | 0 | 0 |
Change From Baseline in Serum Biochemistry (Alkaline Phosphatase [AP], Alanine Aminotransferase [AAT], Lactate Dehydrogenase [LD]) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
| Intervention | units per liter (U/L) (Mean) |
|---|
| AP: Baseline (n= 7,3,7,33,13) | AP: Change at Day 106 (n=1,0,0,27,11) | AP: Change at Day 190 (n= 0,0,0,24,6) | AAT: Baseline (n= 7,3,7,33,13) | AAT: Change at Day 106 (n=1,0,0,27,11 ) | AAT: Change at Day 190 (n= 0,0,0,24,6) | LD: Baseline (n= 7,3,7,33,13) | LD: Change at Day 106 (n= 1,0,0,27,11) | LD: Change at Day 190 (n= 0,0,0,24,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 144 | NA | NA | 17 | NA | NA | 179 | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 533.1 | -134 | NA | 17.6 | 100 | NA | 313.3 | 15 | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 224.6 | NA | NA | 18.9 | NA | NA | 214.4 | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 218.2 | -119.6 | -119.3 | 19.8 | 2.9 | 1.1 | 212.8 | 10.7 | 16.9 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 195.9 | -78.9 | -116.8 | 19.8 | -2.2 | -3.7 | 203.4 | 45.1 | 17.5 |
Change From Baseline in Serum Biochemistry (Albumin, Protein, Hemoglobin) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
| Intervention | gram per liter (G/L) (Mean) |
|---|
| Albumin Baseline (n= 7,3,7,35,13) | Albumin: Change at Day 106 (n=1,0,0,27,11) | Albumin: Change at Day 190 (n= 0,0,0,24,6) | Protein: Baseline (n= 7,3,7,35,13) | Protein: Change at Day 106 (n=1,0,0,27,11 ) | Protein: Change at Day 190 (n= 0,0,0,24,6) | Hemoglobin: Baseline (n= 7,3,7,35,13) | Hemoglobin: Change at Day 106 (n=1,0,0,27,11 ) | Hemoglobin: Change at Day 190 (n= 0,0,0,23,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 43 | NA | NA | 69.7 | NA | NA | 120.67 | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 42 | -2 | NA | 70.3 | 1 | NA | 122.43 | -10 | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 43 | NA | NA | 70.4 | NA | NA | 120.43 | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 42.7 | -1.3 | -2.3 | 68.7 | -3.9 | -5.3 | 122.82 | -8.81 | -13.65 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 42.3 | -1.2 | -0.5 | 69.1 | -3.8 | -3.7 | 120.23 | -14.27 | -10.67 |
Progression Free Survival (PFS) End Point
PFS defined as the time from randomization (randomization referred to the date of treatment assignment) to disease progression (radiological or clinical, whichever was earlier) or death (if death occurred before progression was documented). Subjects without progression or death at the time of analysis were censored at their last date of tumor evaluation. (NCT01106352)
Timeframe: From start of study treatment to 12 months, at every 12 weeks
| Intervention | days (Median) |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 189 |
| Docetaxel 75 mg/m^2 - Safety Cohort | 146 |
Overall Survival Rate
The overall survival (OS) time in days was calculated as number of days since the day of first dose of study medication until the date of death. (NCT01106352)
Timeframe: 12 months
| Intervention | days (Median) |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 89.1 |
| Docetaxel 75 mg/m^2 - Safety Cohort | 90 |
Change From Baseline in Serum Biochemistry (Bilirubin, Creatinine) During the Treatment Period
In the below table, 'n' signifies those subjects who were evaluable for this measure at given time points for each group. (NCT01106352)
Timeframe: Baseline, Day 106 (dose escalation period), and Day 190 (expanded safety cohort)
| Intervention | micromole(s)/litre (Mean) |
|---|
| Bilirubin: Baseline (n= 7,3,7,33,13) | Bilirubin: Change at Day 106 (n= 1,0,0,27,11) | Bilirubin: Change at Day 190 (n= 0,0,0,24,6) | Creatinine: Baseline (n= 7,3,7,33,13) | Creatinine: Change at Day 106 (n= 1,0,0,27,11) | Creatinine: Change at Day 190 (n= 0,0,0,24,6) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 6.7 | NA | NA | 73.67 | NA | NA |
,| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 8.9 | 2 | NA | 92.33 | 63.6 | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 7.1 | NA | NA | 70.86 | NA | NA |
,| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 7.5 | 0.2 | -0.9 | 70.07 | 0.74 | 0.59 |
,| Docetaxel 75 mg/m^2 - Safety Cohort | 7 | -0.8 | 0.3 | 75.5 | -0.7 | -0.17 |
Exploratory Efficacy: Time to Clinical or Radiographic Progression
"Time to first radiologic or clinical progression is determined by one of the following:~For soft tissue lesions, the determination is based on Response Evaluation Criteria in Solid Tumors 1.1.~For bone disease, the determination is based on Prostate Cancer Working Cohort 2 (PCWG2) definitions, which require the appearance of at least 2 new lesions with a confirmatory bone scan at least 6 or more weeks later. For clinical progression, the investigators followed the recommendations of the PCWG25 and used their clinical judgment to determine clinical progression." (NCT01106352)
Timeframe: From start of study treatment to 12 months, at every 12 weeks
| Intervention | days (Median) |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 365 |
| Docetaxel 75 mg/m^2 - Safety Cohort | 284 |
Exploratory Efficacy: Percent Change From Baseline in Circulating Tumor Cells at Day 85
CTCs were measured to follow the evolution of the level of CTCs after treatment. (NCT01106352)
Timeframe: Baseline, Day 85, expanded safety cohort
| Intervention | Percent Change (Mean) |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | -75.3 |
| Docetaxel 75 mg/m^2 - Safety Cohort | -68.4 |
Number of Subjects With Signs of Long-Term Radiation Toxicity
Long-term radiation toxicity included incidence of potential late toxicity, such as new primary cancers and bone marrow changes (acute myelogenous leukemia, myelodysplastic syndrome, and aplastic anemia). (NCT01106352)
Timeframe: From start of study treatment upto 12 months
| Intervention | Participants (Number) |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 2 |
| Docetaxel 75 mg/m^2 - Safety Cohort | 0 |
Number of Subjects With Dose-Limiting Toxicities - Dose Escalation Part
DLT was defined as - Absolute neutrophil count grade greater than or equal to (>=) 4 (Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0: less than [<] 0.5 × 109 per Liter) lasting longer than 7 days without fever despite granulocyte colony-stimulating factor (G-CSF) support). Platelet count Grade >= 4 (CTCAE, v4.0: < 25× 109/L) lasting longer than 7 days. Diarrhea Grade >= 3 (CTAE, v4.0: increase of >= 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared with baseline; limiting self-care in activities of daily living) in spite of optimal use of antidiarrheal medication. Vomiting or constipation Grade >= 4 (CTCAE, v4.0: life-threatening consequences; urgent intervention indicated). Febrile neutropenia Grade >= 3 (CTCAE, v4.0). (NCT01106352)
Timeframe: From randomization until 6 weeks post-injection in all dose cohort of dose-escalation part
| Intervention | Participants (Number) |
|---|
| Alpharadin 25 kBq/kg + Docetaxel 75 mg/m^2 - Dose Escalation | 0 |
| Alpharadin 25 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 0 |
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Dose Escalation | 0 |
Exploratory Efficacy: Time to Prostate-specific Antigen (PSA) Progression
Serum PSA progression defined as two consecutive increases in PSA over a previous reference value within 6 months of first study treatment, each measurement at least 1 week apart. (NCT01106352)
Timeframe: 12 months
| Intervention | days (Median) |
|---|
| Alpharadin 50 kBq/kg + Docetaxel 60 mg/m^2 - Safety Cohort | 200 |
| Docetaxel 75 mg/m^2 - Safety Cohort | 146 |
Overall Survival (OS)
Overall survival (OS) was the duration from enrollment to death from any cause. For participants who were alive, OS is censored at the date of last contact. (NCT01107444)
Timeframe: Randomization to date of death from any cause (up to 21.6 months)
| Intervention | months (Median) |
|---|
| LY2181308 + Docetaxel | 7.9 |
| Docetaxel | 8.8 |
Percent of Participants Having a Partial Response (PR) or a Complete Response (CR)
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. (NCT01107444)
Timeframe: Randomization to the first date of progressive disease (up to 12.1 months)
| Intervention | Percentage of participants (Number) |
|---|
| LY2181308 + Docetaxel | 6.1 |
| Docetaxel | 2.1 |
Pharmacokinetics: Area Under the Concentration Curve From Zero to 4 Hours (AUC[0-4]) for LY2181309 and Docetaxel
Pharmacokinetics: Area Under the Concentration Curve From Zero to 4 hours (AUC[0-4]) for LY2181309 and Docetaxel (NCT01107444)
Timeframe: Docetaxel: Cycle(C)1 Day(D)1:0,1,1.25,1.75,3,4 hours(h);LY2181308 + Docetaxel: C1 D-1:3,4 h;D1:0,3,4 h
| Intervention | nanograms*hours per milliliter (ng*h/mL) (Geometric Mean) |
|---|
| LY2181308 + Docetaxel | 1642 |
| Docetaxel | 1195 |
Progression Free Survival (PFS)
Progression Free Survival (PFS) was defined as the time from date of first dose to the first observation of disease progression or death due to any cause. PFS time was censored at the date of the last assessment visit for participants who were still alive and who did not have documented progressive disease as of the data cut-off date. (NCT01107444)
Timeframe: Randomization to the first date of progressive disease or death from any cause (up to 12.88 months)
| Intervention | Months (Median) |
|---|
| LY2181308 + Docetaxel | 2.83 |
| Docetaxel | 3.35 |
Time to Documented Disease Progression
Time to documented disease progression was defined as the time from the date of randomization to the first date of documented progression. Progressive disease (PD) was defined as at least a 20% increase in sum of longest diameter of target lesions. Time to documented disease progression was censored at the date of the last assessment visit for participants who had not had documented progressive disease as of the data cut-off date. (NCT01107444)
Timeframe: Randomization to the first date of progressive disease (up to 12.9 months)
| Intervention | Months (Median) |
|---|
| LY2181308 + Docetaxel | 2.9 |
| Docetaxel | 3.4 |
Time to Worsening of Symptoms as Defined by Lung Cancer Symptom Score (LCSS) Questionnaire
The worsening of symptoms was defined as a 15-millimeter (mm) increase in any 1 symptom on the LCSS. The LCSS is an assessment used to evaluate 6 major symptoms associated with lung malignancies and their effect on overall symptomatic distress, functional activities, and global quality of life. LCSS consists of 2 scales: 1 completed by the participant and 1 completed by the health care professional (which is the average symptom burden index [ASBI]). Participant-reported outcomes are assessed using 9 visual analog scales (100-mm horizontal line). Participants indicate intensity of response to the items in question (0 = lowest rating, 100 = highest rating). The LCSS total score ranges from 0 (lowest rating) to 100 (highest rating). The LCSS total score was defined as the mean over all 9 items. Time to worsening of symptoms was censored at the date of the last assessment visit for participants who did not experience any worsening of symptoms as of the data cut-off date. (NCT01107444)
Timeframe: Baseline to the worsening of symptoms (up to 4.6 months)
| Intervention | Months (Median) |
|---|
| LY2181308 + Docetaxel | 1.0 |
| Docetaxel | 0.8 |
Time to Objective Tumor Response of Partial Response (PR) or Complete Response (CR)
Time to objective tumor response was defined as the time from the date of randomization to the first date of documented objective tumor response. Time to objective tumor response was censored at the date of the last assessment visit for participants who had not had documented response as of the data cut-off date. 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 the longest diameter of target lesions. (NCT01107444)
Timeframe: Randomization to the date of first response (up to 12.1 months)
| Intervention | Months (Median) |
|---|
| LY2181308 + Docetaxel | NA |
| Docetaxel | NA |
Number of Participants With Characterization of Toxicities as Defined by Common Terminology Criteria for Adverse Events (CTCAE) Coding
"Safety analyses included listings and/or summaries of the following:~CTCAE for laboratory and non-laboratory parameters possibly related to study drug;~CTCAE Grades 3 and 4 for laboratory and non-laboratory parameters possibly related to study drug (Grade 3 - severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care. Grade 4 - life-threatening consequences; urgent intervention indicated);~Dose adjustments due to adverse events (AEs)." (NCT01107444)
Timeframe: Randomization through long-term follow up (up to 21.6 months)
| Intervention | Participants (Count of Participants) |
|---|
| Participants with >= 1 CTCAE | Participants with >= 1 CTCAE Grade 3 or Grade 4 | Participants with Docetaxel Dose Changes Due to AE | Participants with LY2181308 Dose Changes Due to AE |
|---|
| Docetaxel | 42 | 34 | 11 | NA |
,| LY2181308 + Docetaxel | 98 | 76 | 24 | 8 |
Lung Cancer Symptom Scale (LCSS) Average Symptom Burden Index (ASBI) on Cycle 2 Day 1
The worsening of symptoms was defined as a 15-millimeter (mm) increase in any 1 symptom on the Lung Cancer Symptom Scale (LCSS). The LCSS is an assessment used to evaluate 6 major symptoms associated with lung malignancies and their effect on 3 overall symptomatic items: distress, functional activities and global quality of life. LCSS consists of 2 scales: 1 completed by the participant and 1 completed by the health care professional (which is the average symptom burden index [ASBI]). Participant-reported outcomes are assessed using 9 visual analog scales (100-mm horizontal line). Participants indicate intensity of response to the items in question (0 = lowest rating, 100 = highest rating). The LCSS total score ranges from 0 (lowest rating) to 100 (highest rating) and was defined as the mean over all 9 items. ASBI was calculated as the mean of six symptom-specific questions from the LCSS, with scores range from 0 (for best outcome) to 100 (for worst outcome). (NCT01107444)
Timeframe: Cycle 2 Day 1
| Intervention | units on a scale (Median) |
|---|
| LY2181308 + Docetaxel | 22 |
| Docetaxel | 24 |
Duration of Response
Duration of response was measured from the time measurement criteria were met for complete response (CR) or partial response (PR) (whichever was first recorded) until the first date of documented progressive disease (PD) or death. Complete response (CR) was defined as the disappearance of all target lesions; PR was defined as at least a 30% decrease in sum of longest diameter of target lesions; PD was defined as at least a 20% increase in sum of longest diameter of target lesions. Duration of response was censored at the date of the last assessment or follow-up visit for responders who were still alive and had not progressed. (NCT01107444)
Timeframe: Time of response to progressive disease (PD) (approximately 8.7 months)
| Intervention | Months (Median) |
|---|
| LY2181308 + Docetaxel | 2.8 |
| Docetaxel | 5.4 |
Change From Baseline in Tumor Size to the End of Cycle 2
The tumor size was defined as the sum of the longest diameters for the target lesions. The sum of lesion diameters was calculated using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines. The log ratio of tumor size at the end of Cycle 2 to tumor size at baseline was calculated for each participant. (NCT01107444)
Timeframe: Baseline, End of Cycle 2 (1 cycle = 21 days)
| Intervention | Log Ratio of Tumor Size (Mean) |
|---|
| LY2181308 + Docetaxel | 1.06 |
| Docetaxel | 1.01 |
Pharmacokinetics: Area Under the Drug Concentration-Time Curve From Zero to Infinity (AUC[0 ∞]) of LY2181309 and Docetaxel
Pharmacokinetics: Area Under the Drug Concentration-Time Curve From Zero to Infinity (AUC[0 ∞]) of LY2181309 and Docetaxel (NCT01107444)
Timeframe: Docetaxel: Cycle(C)1 Day(D)1:0,1,1.25,1.75,3,4,5,505,513,2521 hours(h);LY2181308 + Docetaxel: C1 D -1:3,4 h;D1:0,3,4,5,5.25,5.75,7,8,120,504,507,509,1008,1512,1515,1517,2016, 2520,2523,2525 h
| Intervention | nanograms*hours per milliliter (ng*h/mL) (Geometric Mean) |
|---|
| LY2181308 + Docetaxel | 1905 |
| Docetaxel | 1778 |
Lung Cancer Symptom Scale (LCSS) Average Total Score at Cycle 2 Day 1
The worsening of symptoms was defined as a 15-millimeter (mm) increase in any 1 symptom on the Lung Cancer Symptom Scale (LCSS). The LCSS is an assessment used to evaluate 6 major symptoms associated with lung malignancies and their effect on 3 overall symptomatic items: distress, functional activities and global quality of life. LCSS consists of 2 scales: 1 completed by the participant and 1 completed by the health care professional (which is the average symptom burden index [ASBI]). Participant-reported outcomes are assessed using 9 visual analog scales (100-mm horizontal line). Participants indicate intensity of response to the items in question (0 = lowest rating, 100 = highest rating). The LCSS total score ranges from 0 (lowest rating) to 100 (highest rating) and was defined as the mean over all 9 items. (NCT01107444)
Timeframe: Cycle 2 Day 1
| Intervention | units on a scale (Median) |
|---|
| LY2181308 + Docetaxel | 27 |
| Docetaxel | 30 |
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With Low HER2 mRNA Levels
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 66.5 |
| Trastuzumab Emtansine + Placebo | 70.1 |
| Trastuzumab Emtansine + Pertuzumab | 62.4 |
Percentage of Participants With Death or Disease Progression According to IRF Assessment Among Those With High HER2 mRNA Levels
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 59.4 |
| Trastuzumab Emtansine + Placebo | 57.6 |
| Trastuzumab Emtansine + Pertuzumab | 56.1 |
Percentage of Participants With Death or Disease Progression According to Investigator Assessment
Tumor assessments were performed by the investigator according to RECIST version 1.1. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 72.1 |
| Trastuzumab Emtansine + Placebo | 70.3 |
| Trastuzumab Emtansine + Pertuzumab | 67.5 |
Percentage of Participants With Death or Disease Progression According to Independent Review Facility (IRF) Assessment
Tumor assessments were performed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Disease progression was defined as a greater than or equal to (≥) 20 percent (%) and 5-millimeter (mm) increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). The percentage of participants with death or disease progression was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 63.3 |
| Trastuzumab Emtansine + Placebo | 64.3 |
| Trastuzumab Emtansine + Pertuzumab | 59.8 |
Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With Low HER2 mRNA Levels
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 61.9 |
| Trastuzumab Emtansine + Placebo | 51.7 |
| Trastuzumab Emtansine + Pertuzumab | 66.1 |
Percentage of Participants With a Best Overall Response of CR or PR According to IRF Assessment Among Those With High Human Epidermal Growth Factor Receptor 2 (HER2) Messenger Ribonucleic Acid (mRNA) Levels
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 75.0 |
| Trastuzumab Emtansine + Placebo | 66.9 |
| Trastuzumab Emtansine + Pertuzumab | 63.9 |
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With Low HER2 mRNA Levels
The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 51.8 |
| Trastuzumab Emtansine + Placebo | 52.9 |
| Trastuzumab Emtansine + Pertuzumab | 45.2 |
Percentage of Participants Who Died Prior to Clinical Cutoff Among Those With High HER2 mRNA Levels
The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 38.8 |
| Trastuzumab Emtansine + Placebo | 41.2 |
| Trastuzumab Emtansine + Pertuzumab | 45.1 |
Percentage of Participants Who Died Prior to Clinical Cutoff
The percentage of participants who died prior to clinical cutoff was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 46.3 |
| Trastuzumab Emtansine + Placebo | 47.7 |
| Trastuzumab Emtansine + Pertuzumab | 46.3 |
Percentage of Participants Who Died at 2 Years
(NCT01120184)
Timeframe: From randomization until 2 years
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 20.3 |
| Trastuzumab Emtansine + Placebo | 20.2 |
| Trastuzumab Emtansine + Pertuzumab | 19.6 |
Percentage of Participants Experiencing Treatment Failure
Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. The percentage of participants with treatment failure was calculated as [number of participants with event divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 85.8 |
| Trastuzumab Emtansine + Placebo | 82.6 |
| Trastuzumab Emtansine + Pertuzumab | 80.2 |
Overall Survival Truncated at 2 Years
Overall Survival truncated at 2 years was defined as the percentage of participants alive at 2 years. (NCT01120184)
Timeframe: From randomization until 2 years
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 79.7 |
| Trastuzumab Emtansine + Placebo | 79.8 |
| Trastuzumab Emtansine + Pertuzumab | 80.4 |
Overall Survival (OS) at Clinical Cutoff
OS was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method. (NCT01120184)
Timeframe: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 50.86 |
| Trastuzumab Emtansine + Placebo | 53.68 |
| Trastuzumab Emtansine + Pertuzumab | 51.78 |
OS at Clinical Cutoff Among Those With Low HER2 mRNA Levels
"OS was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis. Reported upper bound of confidence interval for Trastuzumab Emtansine + Placebo and confidence interval values for Trastuzumab + Taxane and Trastuzumab Emtansine + Pertuzumab are censored values." (NCT01120184)
Timeframe: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 43.96 |
| Trastuzumab Emtansine + Placebo | 47.84 |
| Trastuzumab Emtansine + Pertuzumab | 53.29 |
OS at Clinical Cutoff Among Those With High HER2 mRNA Levels
OS was defined as the time from randomization to death from any cause. Median duration of OS was estimated using Kaplan-Meier analysis. (NCT01120184)
Timeframe: Up to 70 months from randomization until clinical cutoff of 15-May-2016 (every 3 months until death, loss to follow-up, withdrawal, or study termination)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | NA |
| Trastuzumab Emtansine + Placebo | 65.97 |
| Trastuzumab Emtansine + Pertuzumab | 55.39 |
One-Year Survival Rate
The percentage of participants alive at 1 year after randomization was estimated as the one-year survival rate using Kaplan-Meier analysis, and corresponding CIs were computed using Greenwood's estimate of the standard error. (NCT01120184)
Timeframe: From randomization until 1 year
| Intervention | percentage probability of being alive (Number) |
|---|
| Trastuzumab + Taxane | 91.4 |
| Trastuzumab Emtansine + Placebo | 92.4 |
| Trastuzumab Emtansine + Pertuzumab | 91.9 |
Hospitalization Days
Hospitalization was defined as a non-administration-related hospitalization due to serious adverse event, while on study treatment. Reported values represent number of days admitted per participants. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
| Intervention | days (Median) |
|---|
| Trastuzumab + Taxane | 6 |
| Trastuzumab Emtansine + Placebo | 5 |
| Trastuzumab Emtansine + Pertuzumab | 8 |
Duration of Response According to IRF Assessment
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. Duration of response was defined as the time from confirmed PR or CR to first documented disease progression or death from any cause. CR was defined as the disappearance of all target lesions and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. Median duration of response was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method. (NCT01120184)
Timeframe: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 12.5 |
| Trastuzumab Emtansine + Placebo | 20.7 |
| Trastuzumab Emtansine + Pertuzumab | 21.2 |
Percentage of Participants With Grade 3-4 Laboratory Parameters
Laboratory results were graded according to NCI CTCAE version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival. (NCT01120184)
Timeframe: Day 1, 8, and 15 of Cycle 1-3 and on Day 1 of each subsequent cycle up to 50 months from randomization until clinical cutoff of 16-Sept-2014
| Intervention | percentage of participants (Number) |
|---|
| Hemoglobin-Low: Grade 3 | Neutrophils-Low: Grade 3 | Neutrophils-Low: Grade 4 | Platelets-Low: Grade 3 | Platelets-Low: Grade 4 | Alkaline Phosphate-High: Grade 3 | Alanine Transaminase-High: Grade 3 | Alanine Transaminase-High: Grade 4 | Aspartate Aminotransferase-High: Grade 3 | Aspartate Aminotransferase-High: Grade 4 | Creatinine-High: Grade 3 | Creatinine-High: Grade 4 | Potassium-Low: Grade 3 | Potassium-Low: Grade 4 | Total Bilirubin-High: Grade 3 |
|---|
| Trastuzumab + Taxane | 4.3 | 20.2 | 43.8 | 0.9 | 0.3 | 1.1 | 3.4 | 0.0 | 1.1 | 0.0 | 0.9 | 0.0 | 4.3 | 0.6 | 0.3 |
,| Trastuzumab Emtansine + Pertuzumab | 6.9 | 5.0 | 0.8 | 12.9 | 2.5 | 3.0 | 8.0 | 0.6 | 6.9 | 0.3 | 1.1 | 0.3 | 5.2 | 0.6 | 0.3 |
,| Trastuzumab Emtansine + Placebo | 5.8 | 5.5 | 1.9 | 12.7 | 2.8 | 3.9 | 9.1 | 0.3 | 11.9 | 0.3 | 0.3 | 0.0 | 4.7 | 1.7 | 0.3 |
Percentage of Participants Reporting Nausea According to the Relevant Single Items of The FACT Colorectal Cancel (FACT-C) Module
The FACT-C is a self-reported instrument which measures HRQOL pertaining to colorectal cancer. Response options on each question may range from 0 (not at all) to 4 (very much). The percentage of participants with nausea was calculated using following formula: [number of participants with any level of either symptom divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2
| Intervention | percentage of participants (Number) |
|---|
| Nausea, Baseline (n=166,166,150) | Nausea, Cycle 1 Day 8 (n=121,114,95) | Nausea, Cycle 2 Day 1 (n=147,151,138) | Nausea, Cycle 2 Day 8 (n=122,121,105) |
|---|
| Trastuzumab + Taxane | 22.3 | 38.0 | 27.2 | 35.2 |
,| Trastuzumab Emtansine + Pertuzumab | 21.3 | 52.6 | 36.2 | 45.7 |
,| Trastuzumab Emtansine + Placebo | 14.5 | 36.0 | 20.5 | 28.1 |
Percentage of Participants Reporting Diarrhea According to the Relevant Single Items of The FACT-C Module
The FACT-C is a self-reported instrument which measures HRQOL pertaining to colorectal cancer. Response options on each question may range from 0 (not at all) to 4 (very much). The percentage of participants with diarrhea was calculated using following formula: [number of participants with any level of either symptom divided by the number analyzed] multiplied by 100. (NCT01120184)
Timeframe: At Baseline, Day 8 of Cycle 1, and Days 1 and 8 of Cycle 2
| Intervention | percentage of participants (Number) |
|---|
| Diarrhea, Baseline (n=173,170,153) | Diarrhea, Cycle 1 Day 8 (n=124,117,98) | Diarrhea, Cycle 2 Day 1 (n=161,160,144) | Diarrhea, Cycle 2 Day 8 (n=125,123,107) |
|---|
| Trastuzumab + Taxane | 15.0 | 34.7 | 24.2 | 34.4 |
,| Trastuzumab Emtansine + Pertuzumab | 11.8 | 34.7 | 39.6 | 41.1 |
,| Trastuzumab Emtansine + Placebo | 7.6 | 17.9 | 11.3 | 8.1 |
Change From Baseline in Work Productivity According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score
The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. The reported changes represent change from baseline at Cycle 7. The score range for the scales of the WPAI is between 0 (no effect) to 100% (max effect) (NCT01120184)
Timeframe: Baseline, Cycle 7 (Week 18)
| Intervention | percent of work (Mean) |
|---|
| % Work Time Missed at Baseline (n=66,63,67) | Change in % Work Time Missed (n=35,33,36) | % Impairment While Working at Baseline(n=67,64,67) | Change in % Impairment While Working (n=34,32,35) | % Overall Work Impairment at Baseline (n=65,62,66) | Change in % Overall Work Impairment (n=34,31,35) |
|---|
| Trastuzumab + Taxane | 15.3 | 0.4 | 20.0 | 8.8 | 28.5 | 9.1 |
,| Trastuzumab Emtansine + Pertuzumab | 13.6 | -4.3 | 19.9 | -2.7 | 28.1 | -4.6 |
,| Trastuzumab Emtansine + Placebo | 9.5 | -0.0 | 15.3 | -0.3 | 21.2 | -1.1 |
Change From Baseline in Rotterdam Symptom Checklist (RSCL) Activity Level Scale Score
The RSCL is a self-reported instrument which consists of 4 domains including physical symptom distress, psychological distress, activity level, and overall global life quality. Only the activity level scale was collected and assessed. Scores may range from 0 to 100, with higher scores indicating increased burden of disease. Mean RSCL activity scale score changes were calculated as [mean score at the assessment visit minus mean score at Baseline]. The higher the score, the higher the level of impairment or burden. (NCT01120184)
Timeframe: Baseline, Cycle 7 (Week 18)
| Intervention | units on a scale (Mean) |
|---|
| Baseline (n=344,355,344) | Change From Baseline at Cycle 7 (n=261,252,261) |
|---|
| Trastuzumab + Taxane | 85.0 | -1.6 |
,| Trastuzumab Emtansine + Pertuzumab | 85.7 | -0.2 |
,| Trastuzumab Emtansine + Placebo | 85.5 | 2.3 |
Change From Baseline in Activity Impairment According to Work Productivity and Activity Impairment (WPAI) Questionnaire Score
The WPAI is a patient-reported measure which assesses the effect of general health and symptom severity on work productivity and regular activities. The General Health questionnaire asks participants to estimate the number of hours missed from work due to reasons related and unrelated to their health problems, as well as the total number of hours actually worked in the preceding 7-day period. The percentage of participants reporting that they were employed (working for pay) was assessed at baseline was assessed along with Absenteeism (work time missed), Presenteeism (impairment at work / reduced on-the-job effectiveness), Work productivity loss (overall work impairment / absenteeism plus presenteeism), and Activity Impairment. The reported changes represent change from baseline at Cycle 7. The score range for the scales of the WPAI is between 0 (no effect) to 100% (max effect). (NCT01120184)
Timeframe: Baseline, Cycle 7 (Week 18)
| Intervention | units on a scale (Mean) |
|---|
| % Activity Impairment at Baseline (n=312,334,321) | Change in % Activity Impairment (n=227,222,234) |
|---|
| Trastuzumab + Taxane | 32.9 | 4.5 |
,| Trastuzumab Emtansine + Pertuzumab | 32.7 | -3.7 |
,| Trastuzumab Emtansine + Placebo | 33.6 | -5.3 |
Time to Treatment Failure (TTF)
Treatment failure was defined as the discontinuation of all study medications in the treatment arm for any reason including disease progression, treatment toxicity, death, physician decision, or participant withdrawal. TTF was defined as the time from randomization to treatment failure. Median TTF was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 10.2 |
| Trastuzumab Emtansine + Placebo | 12.1 |
| Trastuzumab Emtansine + Pertuzumab | 11.8 |
Time to Deterioration in HRQoL as Assessed by FACT-B TOI-PFB Score
The FACT-B is a self-reported instrument which measures HRQOL of participants with breast cancer. It consists of 5 subscales including PWB, SWB, EWB, FWB, and BCS. The TOI-PFB score is taken by adding the scores from the PWB (7 items), FWB (7 items), and BCS (9 items) subscales. Items are rated from 0 (not at all) to 4 (very much) and a total score is derived. Scores may range from 0 to 92, with higher scores indicating better HRQOL. A 5 point change has been identified as the clinically minimal important difference (CMID) on the FACT-TOI-PFB scale. Time to deterioration was defined as the time from Baseline until the first decrease in FACT-B TOI-PFB score. Median time to deterioration was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method. (NCT01120184)
Timeframe: Baseline up to 39 months from randomization until clinical cutoff of 16-Sept-2014
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 3.6 |
| Trastuzumab Emtansine + Placebo | 7.7 |
| Trastuzumab Emtansine + Pertuzumab | 9.0 |
Progression-Free Survival (PFS) According to IRF Assessment
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding confidence intervals (CIs) were computed using the Brookmeyer-Crowley method. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 13.7 |
| Trastuzumab Emtansine + Placebo | 14.1 |
| Trastuzumab Emtansine + Pertuzumab | 15.2 |
PFS According to IRF Assessment Among Those With Low HER2 mRNA Levels
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 12.4 |
| Trastuzumab Emtansine + Placebo | 10.2 |
| Trastuzumab Emtansine + Pertuzumab | 14.5 |
PFS According to IRF Assessment Among Those With High HER2 mRNA Levels
Tumor assessments were performed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 15.9 |
| Trastuzumab Emtansine + Placebo | 18.6 |
| Trastuzumab Emtansine + Pertuzumab | 18.7 |
PFS According to Investigator Assessment
Tumor assessments were performed by the investigator according to RECIST version 1.1. PFS was defined as the time from randomization to first documented disease progression or death from any cause. Disease progression was defined as a ≥20% and 5-mm increase in sum of diameters of target lesions, taking as reference the smallest sum obtained during the study, or appearance of new lesion(s). Median duration of PFS was estimated using Kaplan-Meier analysis, and corresponding CIs were computed using the Brookmeyer-Crowley method. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | months (Median) |
|---|
| Trastuzumab + Taxane | 12.5 |
| Trastuzumab Emtansine + Placebo | 14.1 |
| Trastuzumab Emtansine + Pertuzumab | 14.8 |
Percentage of Participants With Objective Response According to IRF Assessment
Objective response was defined as having complete response (CR) or partial response (PR), assessed according to RECIST version 1.1, using radiographic images submitted to the IRF up to and including the confirmatory tumor assessment 4 to 6 weeks after study drug discontinuation. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the objective response rate [ORR]) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method. (NCT01120184)
Timeframe: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 67.9 |
| Trastuzumab Emtansine + Placebo | 59.7 |
| Trastuzumab Emtansine + Pertuzumab | 64.2 |
Percentage of Participants With Objective Response According to Investigator Assessment
Objective response was defined as having CR or PR, assessed according to RECIST version 1.1, by investigator. CR was defined as the disappearance of all target and non-target lesions and short-axis reduction in pathological lymph nodes to <10 mm. PR was defined as a ≥30% decrease in sum of diameters of target lesions, taking as reference the Baseline sum. Response was determined using 2 consecutive tumor assessments at least 4 weeks apart. The percentage of participants with a best overall response of CR or PR (ie, the ORR) was calculated as [number of participants meeting the respective criteria divided by the number analyzed] multiplied by 100. Corresponding CIs were computed using the Blyth-Still-Casella exact method. (NCT01120184)
Timeframe: Up to 46 months from randomization until clinical cutoff of 16-Sept-2014 (at Screening, every 9 weeks for 81 weeks, then every 12 weeks thereafter and/or up to 42 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 69.3 |
| Trastuzumab Emtansine + Placebo | 64.6 |
| Trastuzumab Emtansine + Pertuzumab | 67.5 |
Percentage of Participants With Hospitalization
Hospitalization was defined as a non-administration-related hospitalization due to serious adverse event, while on study treatment. (NCT01120184)
Timeframe: Up to 48 months from randomization until clinical cutoff of 16-Sept-2014
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 21.8 |
| Trastuzumab Emtansine + Placebo | 20.2 |
| Trastuzumab Emtansine + Pertuzumab | 22.1 |
Percentage of Participants With Grade 5 Adverse Events
Adverse events were graded according to NCI CTCAE version 4.0. Grade 5 adverse events are those events which led to death. (NCT01120184)
Timeframe: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 1.7 |
| Trastuzumab Emtansine + Placebo | 1.1 |
| Trastuzumab Emtansine + Pertuzumab | 1.9 |
Percentage of Participants With Grade ≥3 Adverse Events
Adverse events were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activity of daily living with inability to perform bathing, dressing and undressing, feeding self, using the toilet, taking medications but not bedridden. Grade 4: An immediate threat to life. Urgent medical intervention is required in order to maintain survival. Grade 5: Death. (NCT01120184)
Timeframe: Up to 50 months from randomization until clinical cutoff of 16-Sept-2014 (continuously until 28 days after last dose
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab + Taxane | 54.1 |
| Trastuzumab Emtansine + Placebo | 45.4 |
| Trastuzumab Emtansine + Pertuzumab | 46.2 |
Double-Blind Phase: Number of Participants With Febrile Neutropenia
Febrile neutropenia was defined as an imputed or observed ANC <0.5 x 10^9/L and body temperature >38.5 degrees celsius (°C) occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported. (NCT01126190)
Timeframe: Cycles 1-4 (each cycle = 21 days)
| Intervention | participants (Number) |
|---|
| Double-Blind Phase: Pegfilgrastim | 4 |
| Double-Blind Phase: Neugranin 40 mg | 2 |
Double-Blind Phase: Duration of Severe Neutropenia in Cycle 1
Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count [ANC] <0.5 x 10^9/liter [L]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10^9/L within the cycle. (NCT01126190)
Timeframe: Cycle 1 (cycle length = 21 days)
| Intervention | days (Mean) |
|---|
| Double-Blind Phase: Pegfilgrastim | 1.0 |
| Double-Blind Phase: Neugranin 40 mg | 1.1 |
Open-Label Phase: Number of Participants With Febrile Neutropenia
Febrile neutropenia was defined as an imputed or observed ANC <0.5 x 10^9/L and body temperature >38.5 °C occurring on the same day and for more than one hour (axillary measurement). Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported. (NCT01126190)
Timeframe: Cycles 1-4 (each cycle = 21 days)
| Intervention | participants (Number) |
|---|
| Open-Label Phase: Neugranin 40 mg | 2 |
Open-Label Phase: Duration of Severe Neutropenia in Cycle 1
Severe neutropenia was defined as Grade 4 neutropenia (ANC <0.5 x 10^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10^9/L within the cycle. There was no planned statistical analysis for the open-label phase arm. (NCT01126190)
Timeframe: Cycle 1 (cycle length = 21 days)
| Intervention | days (Mean) |
|---|
| Open-Label Phase: Neugranin 40 mg | 1.0 |
Overall 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 (NCT01129206)
Timeframe: Approximately three years
| Intervention | patients (Number) |
|---|
| Stable disease | Progressive disease |
|---|
| Arm I: Pralatrexate and Docetaxel | 2 | 4 |
Correlation of FDG PET Response With Response Rate
Radiological assessment of tumor response was performed by computed tomography (CT) and positron emission tomography (PET) every four cycles of therapy and responses were measured according to RECIST and PERCIST criteria. (NCT01129206)
Timeframe: Approximately three years
| Intervention | patients (Number) |
|---|
| Progressive Disease | Stable Disease | Partial Response |
|---|
| PERCIST Criteria Per PET | 0 | 2 | 2 |
,| RECIST Criteria Per CT | 4 | 2 | 0 |
Progression-free Survival (PFS)
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 (NCT01129206)
Timeframe: Approximately three years
| Intervention | months (Median) |
|---|
| Arm I: Pralatrexate and Docetaxel | 1.9 |
Overall Survival (OS)
OS was determined from the date of start of therapy to death frm any cause. (NCT01129206)
Timeframe: Approximately five years
| Intervention | months (Median) |
|---|
| Arm I | 5.5 |
Overall Survival
Overall survival is defined as the time from randomization to death or the date of last known alive. (NCT01145508)
Timeframe: Assessed every 3 months for 2 years, and then every 6 months for 3 years
| Intervention | Months (Median) |
|---|
| Arm A (Vaccine and Chemotherapy) | 20.8 |
| Arm B (Chemotherapy) | NA |
Percentage of Participants Achieving Disease Control (Disease Control Rate)
Participants achieved disease control if they had a best overall response of PR, CR or stable disease (SD). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the ULN). SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control=(number of participants with CR, PR, or SD)/(number of participants assessed)*100. (NCT01168973)
Timeframe: Baseline to measured PD (up to 29 months)
| Intervention | percentage of participants (Number) |
|---|
| Ramucirumab and Docetaxel | 64.0 |
| Placebo and Docetaxel | 52.6 |
Number of Participants With Anti-Ramucirumab Antibodies
The number of participants who had treatment-emergent or follow-up emergent anti-drug antibodies (ADA) is reported. Participants with treatment-emergent ADA were defined as participants who had any sample from baseline through Cycle 5 pre-infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). Participants with follow-up emergent ADA were defined as participants who had any sample during 30 days post last infusion that was a 4-fold increase (2 dilution increase) in immunogenicity titer over the baseline titer. (NCT01168973)
Timeframe: Baseline, prior to infusion for week 4 and 8 (cycles 3 and 5), and 30 days following last infusion (up to Cycle 38, 21 days/cycle)
| Intervention | participants (Number) |
|---|
| Treatment-Emergent ADA (n=599, 598) | Follow-Up Emergent ADA (n=506, 481) |
|---|
| Placebo and Docetaxel | 16 | 16 |
,| Ramucirumab and Docetaxel | 9 | 9 |
Progression-Free Survival (PFS) Time
PFS time was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was 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 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD who were alive at the end of the follow-up period (or lost to follow-up) were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization. (NCT01168973)
Timeframe: Randomization to measured PD or date of death from any cause (up to 29 months)
| Intervention | months (Median) |
|---|
| Ramucirumab and Docetaxel | 4.5 |
| Placebo and Docetaxel | 3.0 |
Change From Baseline to 30-Day Follow-Up Visit on European Quality of Life Questionnaire-5 Dimension (EQ-5D) Health State Scores
The EQ-5D is a quality-of-life instrument that consists of 2 parts. The first part (Health State Index score) allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 3 (no problem, some problems, and extreme problems, respectively). These combinations of attributes were converted into a weighted Health State Index score according to a United Kingdom population-based algorithm; the possible values for the Health State Index score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). The second part of the EQ-5D was a VAS that allowed participants to rate their present health condition. Possible EQ-5D VAS scores ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). (NCT01168973)
Timeframe: Baseline, 30 days following last infusion (up to Cycle 38, 21 days/cycle)
| Intervention | units on a scale (Mean) |
|---|
| Health State Index Score (n=266, 272) | Health State VAS Score (n=272, 254) |
|---|
| Placebo and Docetaxel | -0.126 | -6.1 |
,| Ramucirumab and Docetaxel | -0.140 | -5.9 |
Maximum and Minimum Serum Concentrations (Cmax and Cmin) of Ramucirumab
(NCT01168973)
Timeframe: Prior to infusion and 1 hour following infusion for 4 and 8 (cycles 3 and 5 at 21 days/cycle)
| Intervention | micrograms per milliliter (mcg/mL) (Geometric Mean) |
|---|
| Cmax at Cycle 3 | Cmin at Cycle 3 | Cmax at Cycle 5 | Cmin at Cycle 5 |
|---|
| Ramucirumab and Docetaxel | 262 | 28.3 | 237 | 38.4 |
Maximum Improvement on Lung Cancer Symptom Scale (LCSS)
The LCSS consisted of 9 items: 6 items focused on lung cancer symptoms [loss of appetite, fatigue, cough, dyspnea (shortness of breath), hemoptysis (blood in sputum), and pain] and 3 items were global items (symptom distress, interference with activity level, and global quality of life). Participant responses to each item were measured using visual analogue scales (VAS) with 100-mm lines. A higher score for any item represented a higher level of symptoms/problems. The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom items of the LCSS, and the Total LCSS was the mean of all 9 LCSS items. ASBI and Total LCSS were not computed for a participant if he/she had 1 or more missing values for the 6 and 9 items, respectively. Maximum improvement in LCSS scores, ASBI, and Total LCSS score was the largest decrease from baseline for each variable, which was the smallest (most negative or smallest positive) non-missing value among all change from baseline values for each variable. (NCT01168973)
Timeframe: Baseline, Day 21 of each cycle, and 30 days following last infusion (up to Cycle 38, 21 days/cycle)
| Intervention | mm (Mean) |
|---|
| Loss of Appetite (n=473, 471) | Fatigue (n=473, 472) | Cough (n=476, 473) | Dyspnea (n=472, 477) | Hemoptysis (n=475, 475) | Pain (n=476, 475) | Symptom Distress (n=474, 472) | Interference With Activity Level (n=474, 472) | Global Quality of Life (n=467, 469) | ASBI (n=455, 456) | Total LCSS (n=446, 446) |
|---|
| Placebo and Docetaxel | -11.0 | -12.0 | -14.3 | -10.5 | -1.1 | -11.5 | -12.2 | -7.9 | -8.9 | -6.9 | -6.4 |
,| Ramucirumab and Docetaxel | -10.9 | -12.1 | -13.8 | -11.0 | -1.4 | -11.3 | -10.7 | -8.5 | -10.4 | -6.1 | -5.2 |
Number of Participants Who Had Treatment-Emergent Adverse Events (TEAEs) or Died
Data presented are the number of participants who experienced at least 1 TEAE, Grade 3, 4, or 5 TEAE, treatment-emergent serious adverse event (SAE), TEAE leading to discontinuation of study treatment (ramucirumab/placebo or docetaxel), and TEAE leading to death. Clinically significant events were defined as treatment-emergent SAEs and other non-serious adverse events (AEs) regardless of causality. A summary of SAEs and other non-serious AEs, regardless of causality, is located in the Reported Adverse Events module. (NCT01168973)
Timeframe: First infusion up to 30 days following last infusion (up to Cycle 38, 21 days/cycle)
| Intervention | participants (Number) |
|---|
| At least 1 TEAE | At least 1 Grade 3, 4, or 5 TEAE | At least 1 treatment-emergent SAE | TEAE leading to study drug discontinuation | TEAE leading to death | Deaths While On Treatment | Deaths During 30 Days Post Last Dose |
|---|
| Placebo and Docetaxel | 594 | 444 | 262 | 32 | 35 | 451 | 58 |
,| Ramucirumab and Docetaxel | 613 | 495 | 269 | 58 | 34 | 428 | 53 |
Overall Survival
Overall survival was the time from randomization until 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 participant was known to be alive. (NCT01168973)
Timeframe: Randomization to date of death from any cause (up to 34 months)
| Intervention | months (Median) |
|---|
| Ramucirumab and Docetaxel | 10.5 |
| Placebo and Docetaxel | 9.1 |
Percentage of Participants Achieving an Objective Response (Objective Response Rate)
Participants achieved an objective response if they had a best overall response of partial response (PR) or complete response (CR). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels [if tumor markers were initially above the upper limit of normal (ULN)]. The percentage of participants who achieved an objective response=(number of participants with CR or PR)/(number of participants assessed)*100. (NCT01168973)
Timeframe: Baseline to measured PD (up to 29 months)
| Intervention | percentage of participants (Number) |
|---|
| Ramucirumab and Docetaxel | 22.9 |
| Placebo and Docetaxel | 13.6 |
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
| Intervention | percentage of participants (Number) |
|---|
| US/Korea | 54 |
| Japan | 71 |
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.
| Intervention | percentage of participants (Number) |
|---|
| US/Korea | 43 |
| Japan | 53 |
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
| Intervention | months (Median) |
|---|
| US/Korea | 11.0 |
| Japan | 12.1 |
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.
| Intervention | months (Median) |
|---|
| US/Korea | 22.6 |
| Japan | 25.6 |
Frequency and Severity of Toxicity
Grade 3 or higher adverse events were graded by CTC AE v4 (NCT01196429)
Timeframe: Each cycle while on treatment
| Intervention | participants (Number) |
|---|
| Neutrophil count decreased | White blood cell decreased | Anemia | Platelet count decreased | Hypertension | hypertriglyceridemia | Mucositis oral | Febrile neutropenia | Diarrhea | Hypokalemia | Hyperglycemia | Abdominal pain | Lymphocyte count decreased | Nausea | Urinary tract infection | GGT increased | Edema limbs | Fatigue | Fever | Non-cardiac chest pain | Cholesterol high | Weight gain | Hypoalbuminemia | Hyponatremia | Hypophosphatemia | Peripheral Sensory neuropathy | Cough | Dyspnea | Pharyngeal mucositis | Rash maculo-papular | Colonic perforation | Constipation | Ileus | Oral pain | Small intestinal obstruction | Vomiting | Pain | Cholecystitis | Hepatobiliary disorders-other | Appendicitis perforated | Kidney infection | Lung infection | Peripherl nerve infection | Pharyngitis | Skin infection | Infections and infestations -other | Alanine aminotransferase increased | Aspartate aminotransferase increased | Creatiine increased | Anorexia | Dehydration | Hypermagnesemia | Back Pain | Bone Pain | Flank pain | Pain in Extremity | Dizziness | Paresthesia | Vasovagal reaction | Anxiety | Dysparenuia | Pneumonitis | Sore throat | Hypotension | Lymphocele |
|---|
| Japan | 42 | 32 | 13 | 10 | 10 | 7 | 5 | 5 | 2 | 4 | 2 | 1 | 2 | 2 | 0 | 3 | 0 | 1 | 1 | 0 | 2 | 0 | 1 | 0 | 2 | 2 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
,| US/Korea | 36 | 27 | 9 | 10 | 4 | 6 | 5 | 4 | 6 | 3 | 4 | 3 | 2 | 1 | 3 | 0 | 2 | 1 | 1 | 2 | 0 | 2 | 1 | 2 | 0 | 0 | 2 | 2 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 |
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR)
Best overall response (complete response [CR]/partial response [PR]) was defined as the best response recorded from the start of the treatment until disease progression (PD). Best response in this trial was defined as the best response observed at any post-treatment visits. 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 less than [<] 10 mm). No new lesions. PR was defined as greater than or equal to [>=] 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. (NCT01204697)
Timeframe: From randomization until progressive disease or death, assessed up to 18 months
| Intervention | percentage of participants (Number) |
|---|
| Erlotinib | 2.8 |
| Docetaxel and Erlotinib | 8.1 |
Percentage of Participants Free From Disease Progression or Death at 6 Months
According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1, progressive Disease (PD) is defined as: for Target Lesions - 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 also demonstrate an absolute increase of at least 5 millimeter (mm). (Note: the appearance of one or more new lesions is also considered progression). For Non-Target Lesions - Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered progression). (NCT01204697)
Timeframe: Month 6
| Intervention | percentage of participants (Number) |
|---|
| Erlotinib | 8.3 |
| Docetaxel and Erlotinib | 8.1 |
Overall Survival (OS)
Overall survival (OS) was defined as the interval (in days) between the date of randomization and death from any cause. Participants alive at the time of the analysis were censored at the date they were last known to be alive. OS was assessed using the Kaplan-Meier method. (NCT01204697)
Timeframe: From randomization until death, assessed up to 18 months
| Intervention | months (Median) |
|---|
| Erlotinib | 5.61 |
| Docetaxel and Erlotinib | 8.95 |
Duration of Response (DoR)
Duration of response (DoR) was defined as the interval (in days) from first documentation of a response (CR/PR depending on which occurred first) to the date of the first documentation of disease progression or death from any cause. Participants presenting a response were considered as censored at the date of the last assessment with a documentation of non-progression. DoR (days) = (Date of PD/death - Date of CR/PR) + 1. Assessments were performed according to RECIST Version 1.1. DoR was assessed using the Kaplan-Meier method. Detailed definitions of CR and PR are provided in Outcome Measure 4. (NCT01204697)
Timeframe: From randomization until progressive disease or death, assessed up to 18 months
| Intervention | months (Median) |
|---|
| Erlotinib | NA |
| Docetaxel and Erlotinib | 8.69 |
Progression-free Survival (PFS)
Progression-free Survival (PFS) was defined as the interval (in days) between the date of randomization and the first documentation of progressive disease or death from any cause. Participants alive and progression-free were considered as censored at the date of the last tumor assessment when the participant was known to be progression-free. Participants without post-baseline tumor assessment, but known to be alive, were censored at the time of randomization. PFS (days) = (Date of Event - Date of Randomization) + 1. PFS was assessed using the Kaplan-Meier method. Detailed definition of PD is provided in Outcome Measure 1. (NCT01204697)
Timeframe: From randomization until progressive disease or death, assessed up to 18 months
| Intervention | months (Median) |
|---|
| Erlotinib | 2.33 |
| Docetaxel and Erlotinib | 2.82 |
Percentage of Participants With Disease Control
Disease control was defined as PR, CR, or SD. Participants who did not achieve a CR or PR or SD were counted as non-responders in the analysis of disease control. According to RECIST Version 1.1, SD was defined as not qualifying for CR, PR, and PD. Detailed definitions of CR and PR are provided in Outcome Measure 4. (NCT01204697)
Timeframe: From randomization until progressive disease or death, assessed up to 18 months
| Intervention | percentage of participants (Number) |
|---|
| Erlotinib | 41.7 |
| Docetaxel and Erlotinib | 37.8 |
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
| Intervention | Subjects (Number) |
|---|
| Cohort A-GSK2302024A Group | 15 |
| Cohort A-Placebo Group | 5 |
| Cohort B-GSK2302024A Group | 9 |
| Cohort B-Placebo Group | 6 |
| Cohort C-GSK2302024A Group | 11 |
| Cohort C-Placebo Group | 4 |
| Cohort D-GSK2302024A-D14 Group | 7 |
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)
| Intervention | Subjects (Number) |
|---|
| Cohort A-GSK2302024A Group | 0 |
| Cohort A-Placebo Group | 0 |
| Cohort B-GSK2302024A Group | 1 |
| Cohort B-Placebo Group | 0 |
| Cohort C-GSK2302024A Group | 1 |
| Cohort C-Placebo Group | 0 |
| Cohort D-GSK2302024A-D14 Group | 0 |
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
| Intervention | Subjects (Number) |
|---|
| Any AE(s) Grade 1 | Any AE(s) Grade 2 | Any AE(s) Grade 3 | Any AE(s) Grade 4 | Any AE(s) Grade 5 | Any AE(s) |
|---|
| Cohort A-GSK2302024A Group | 6 | 6 | 3 | 0 | 0 | 15 |
,| Cohort A-Placebo Group | 1 | 4 | 0 | 0 | 0 | 5 |
,| Cohort B-GSK2302024A Group | 0 | 6 | 0 | 2 | 1 | 9 |
,| Cohort B-Placebo Group | 0 | 0 | 5 | 1 | 0 | 6 |
,| Cohort C-GSK2302024A Group | 0 | 4 | 3 | 4 | 0 | 11 |
,| Cohort C-Placebo Group | 0 | 3 | 0 | 1 | 0 | 4 |
,| Cohort D-GSK2302024A-D14 Group | 0 | 2 | 1 | 4 | 0 | 7 |
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)
| Intervention | Subjects (Number) |
|---|
| Cohort A-GSK2302024A Group | 10 |
| Cohort A-Placebo Group | 0 |
| Cohort B-GSK2302024A Group | 0 |
| Cohort B-Placebo Group | 0 |
| Cohort C-GSK2302024A Group | 6 |
| Cohort C-Placebo Group | 0 |
| Cohort D-GSK2302024A-D14 Group | 2 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 15 | 0 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 7 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 9 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 11 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 4 | 0 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 4 | 0 | 0 | 0 | 0 | 4 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 12 | 2 | 0 | 0 | 0 | 1 |
,| Cohort A-Placebo Group | 5 | 1 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 8 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 4 | 2 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 6 | 5 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 2 | 2 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 1 | 2 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 10 | 5 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 5 | 1 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 8 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 7 | 4 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 3 | 1 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 1 | 2 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 12 | 2 | 1 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 7 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 1 | 7 | 0 | 1 | 0 | 0 |
,| Cohort B-Placebo Group | 0 | 4 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 0 | 7 | 4 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 0 | 3 | 1 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 2 | 2 | 0 | 0 | 0 | 4 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 12 | 3 | 1 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 4 | 2 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 8 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 7 | 4 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 1 | 3 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 2 | 1 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 15 | 0 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 5 | 1 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 9 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 11 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 2 | 0 | 1 | 1 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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)
| Intervention | Subjects (Number) |
|---|
| Cohort A-GSK2302024A Group | 3 |
| Cohort A-Placebo Group | 0 |
| Cohort B-GSK2302024A Group | 4 |
| Cohort B-Placebo Group | 2 |
| Cohort C-GSK2302024A Group | 5 |
| Cohort C-Placebo Group | 1 |
| Cohort D-GSK2302024A-D14 Group | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 9 | 5 | 1 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 4 | 2 | 1 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 0 | 3 | 5 | 1 | 0 | 0 |
,| Cohort B-Placebo Group | 0 | 2 | 2 | 2 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 2 | 3 | 5 | 1 | 0 | 0 |
,| Cohort C-Placebo Group | 1 | 1 | 1 | 1 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 1 | 1 | 2 | 0 | 0 | 4 |
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
| Intervention | Subjects (Number) |
|---|
| Partial respose | Complete response |
|---|
| Cohort A-GSK2302024A Group | 4 | 0 |
,| Cohort A-Placebo Group | 3 | 0 |
,| Cohort B-GSK2302024A Group | 5 | 0 |
,| Cohort B-Placebo Group | 3 | 2 |
,| Cohort C-GSK2302024A Group | 3 | 6 |
,| Cohort C-Placebo Group | 1 | 3 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 1 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 13 | 2 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 7 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 6 | 2 | 1 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 3 | 2 | 1 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 7 | 4 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 2 | 1 | 1 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 0 | 1 | 0 | 3 | 0 | 4 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 14 | 1 | 0 | 0 | 0 | 3 |
,| Cohort A-Placebo Group | 3 | 3 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 8 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 11 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 4 | 0 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 15 | 0 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 5 | 1 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 7 | 1 | 1 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 10 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 4 | 0 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Any SAE(s) Grade 1 | Any SAE(s) Grade 2 | Any SAE(s) Grade 3 | Any SAE(s) Grade 4 | Any SAE(s) Grade 5 | Any SAE(s) |
|---|
| Cohort A-GSK2302024A Group | 0 | 1 | 2 | 0 | 0 | 3 |
,| Cohort A-Placebo Group | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 0 | 1 | 0 | 2 | 1 | 4 |
,| Cohort B-Placebo Group | 0 | 0 | 1 | 1 | 0 | 2 |
,| Cohort C-GSK2302024A Group | 0 | 0 | 1 | 4 | 0 | 5 |
,| Cohort C-Placebo Group | 0 | 0 | 0 | 1 | 0 | 1 |
,| Cohort D-GSK2302024A-D14 Group | 0 | 0 | 1 | 4 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 14 | 1 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 4 | 2 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 9 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 10 | 0 | 1 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 4 | 0 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 13 | 1 | 1 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 6 | 0 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 9 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 5 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 9 | 2 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 3 | 1 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 15 | 0 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 6 | 0 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 9 | 0 | 1 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 10 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 4 | 0 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 12 | 3 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 6 | 0 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 5 | 3 | 1 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 4 | 1 | 1 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 10 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 3 | 1 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 11 | 4 | 0 | 0 | 0 | 4 |
,| Cohort A-Placebo Group | 4 | 2 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 8 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 5 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 10 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 3 | 1 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 15 | 0 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 6 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 9 | 0 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 11 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 4 | 0 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 4 | 0 | 0 | 0 | 0 | 4 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 15 | 0 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 6 | 0 | 0 | 0 | 0 | 1 |
,| Cohort B-GSK2302024A Group | 5 | 4 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 6 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 11 | 0 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 4 | 0 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 3 | 0 | 0 | 0 | 0 | 5 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 14 | 1 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 6 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 8 | 1 | 0 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 5 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 5 | 5 | 1 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 2 | 2 | 0 | 0 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 2 | 2 | 0 | 0 | 0 | 4 |
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
| Intervention | Subjects (Number) |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade Unknown |
|---|
| Cohort A-GSK2302024A Group | 12 | 3 | 0 | 0 | 0 | 0 |
,| Cohort A-Placebo Group | 6 | 0 | 1 | 0 | 0 | 0 |
,| Cohort B-GSK2302024A Group | 7 | 1 | 1 | 0 | 0 | 0 |
,| Cohort B-Placebo Group | 5 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-GSK2302024A Group | 10 | 1 | 0 | 0 | 0 | 0 |
,| Cohort C-Placebo Group | 3 | 0 | 0 | 1 | 0 | 0 |
,| Cohort D-GSK2302024A-D14 Group | 0 | 0 | 1 | 0 | 3 | 4 |
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).
| Intervention | percentage of participants (Number) |
|---|
| TPF Induction Chemotherapy Followed by Chemoradiotherapy | 100 |
Neutropenia Grade 3-4
Toxicity (CECAE ver 4.0) and Safety (NCT01243775)
Timeframe: 2 years
| Intervention | participants (Number) |
|---|
| Belotaxel Plus Belloxa | 17 |
Progression Free Survival
(NCT01243775)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Belotaxel Plus Belloxa | 3.6 |
Overall Survival
(NCT01243775)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Belotaxel Plus Belloxa | 10.9 |
Response Rate
RECIST version 1.1 (NCT01243775)
Timeframe: 6th week
| Intervention | participants (Number) |
|---|
| Belotaxel Plus Belloxa | 11 |
Pathologic Complete Response Was Assessed by Rigorous Pathological Examination by One of Two Pathologists
One of two pathologists (SR, EG), assigned the Gleason scores for each patient from pre-treatment prostate biopsies and assessed pathological staging on post- prostatectomy specimens. Staging including a description of all tumor foci within the gland, presence or absence of perineural invasion and/or lymphovascular invasion, presence of extraprostatic extension of tumor (including seminal vesicle invasion), and margin status. The pathologists reviewed the presence or absence of cancer in each prostate gland removed on the study patients. RECIST has to my knowledge not been used for pathological examination in neoadjuvant studies. 0 out of 28 participants acheived complete response. RECIST is not appropriate as cancer within the gland at the time of treatment is not measurable by RECIST. The primary outcome is a pathological complete response. (NCT01250717)
Timeframe: status post prostectomy
| Intervention | participants (Number) |
|---|
| Docetaxel Followed by Radical Prostatectomy | 0 |
Number of Participants With Dose Limiting Toxicities (DLTs) in Process for the Determination of the Maximum Tolerated Dose (MTD).
DLT was based on following criterions: 1. Grade 4 uncomplicated (not associated with fever >38.5° C (Celsius)) neutropenia for ≥7 days. 2. Grade 3 or 4 neutropenia concomitant with fever >38.5º C or Grade ≥3 infection. 3. Platelet count of <25x 10^9/L or <50x 10^9/L with bleeding requiring whole blood transfusion. 4. Grade ≥3 non-haematological toxicity (except untreated nausea, untreated vomiting, or untreated diarrhoea). 5. Grade ≥2 decrease in cardiac left ventricular function. 6. Grade ≥2 worsening of renal function as measured by serum creatinine, newly developed proteinuria, or a newly developed decrease in glomerular filtration rate. Toxicity grading was based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 3.0 (NCT01251653)
Timeframe: 3 weeks
| Intervention | Participants (Number) |
|---|
| Afatinib 30mg and Gemcitabine 1000mg | 0 |
| Afatinib 30mg and Gemcitabine 1250mg | 1 |
| Afatinib 40mg and Gemcitabine 1000mg | 1 |
| Afatinib 40mg and Gemcitabine 1250mg | 2 |
| Afatinib 50mg and Gemcitabine 1250mg | 2 |
| Afatinib 30mg and Docetaxel 60mg | 4 |
| Afatinib 30mg and Docetaxel 75mg | 6 |
| Afatinib 40mg and Docetaxel 75mg | 5 |
| Afatinib 50mg and Docetaxel 75mg | 1 |
Total Clearance (CL) of Docetaxel
Total Clearance (CL) of Docetaxel from plasma. (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55
| Intervention | mL/min (Geometric Mean) |
|---|
| Docetaxel 60mg With Afatinib 30mg | 811.0 |
| Docetaxel 60mg Without Afatinib | 671.0 |
| Docetaxel 75mg With Afatinib 30mg | 886.0 |
| Docetaxel 75mg Without Afatinib | 892.0 |
Volume of Distribution at Steady State (Vss) of Gemcitabine
Apparent volume of distribution at steady state (Vss) of Gemcitabine. (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3
| Intervention | L (Geometric Mean) |
|---|
| Gemcitabine 1000mg With Afatinib 40 mg | 90.5 |
| Gemcitabine 1000mg Without Afatinib | 106.0 |
Best Overall Response According to RECIST v1.1 Criteria
Best overall response (according to Response Evaluation Criteria in Solid Tumours [RECIST] version 1.1) was the best response recorded at any time from the date of the first administration of afatinib or gemcitabine/docetaxel to the end of treatment (EOT). Partial response is for patients with measurable disease. Missing categories signifies that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. (NCT01251653)
Timeframe: From first drug administration until 28 days after last drug administration, up to 717 days.
| Intervention | Participants (Number) |
|---|
| Complete response (CR) | Partial response | Stable disease/ Non-CR/Non-PD | Progressive disease (PD) | Not evaluable | Missing |
|---|
| Afatinib 30mg and Docetaxel 60mg | 0 | 1 | 9 | 8 | 0 | 0 |
,| Afatinib 30mg and Docetaxel 75mg | 0 | 5 | 8 | 4 | 0 | 1 |
,| Afatinib 30mg and Gemcitabine 1000mg | 0 | 0 | 2 | 1 | 0 | 0 |
,| Afatinib 30mg and Gemcitabine 1250mg | 0 | 1 | 3 | 3 | 0 | 1 |
,| Afatinib 40mg and Docetaxel 75mg | 0 | 4 | 5 | 2 | 0 | 1 |
,| Afatinib 40mg and Gemcitabine 1000mg | 0 | 4 | 9 | 6 | 0 | 1 |
,| Afatinib 40mg and Gemcitabine 1250mg | 0 | 0 | 5 | 1 | 0 | 0 |
,| Afatinib 50mg and Docetaxel 75mg | 0 | 0 | 2 | 4 | 0 | 0 |
,| Afatinib 50mg and Gemcitabine 1250mg | 0 | 0 | 0 | 2 | 0 | 0 |
Cmax of Gemcitabine
Maximum concentration of Gemcitabine in plasma. (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3
| Intervention | ng/mL (Geometric Mean) |
|---|
| Gemcitabine 1000mg With Afatinib 40 mg | 16000.0 |
| Gemcitabine 1000mg Without Afatinib | 13500.0 |
Duration of Disease Control According to RECIST v1.1
Duration of disease control according to RECIST v1.1. (NCT01251653)
Timeframe: From the first administration of study medication to the time of disease progression or death
| Intervention | Days (Mean) |
|---|
| Afatinib 30mg and Gemcitabine 1000mg | 119.5 |
| Afatinib 30mg and Gemcitabine 1250mg | 210.0 |
| Afatinib 40mg and Gemcitabine 1000mg | 119.7 |
| Afatinib 40mg and Gemcitabine 1250mg | 77.4 |
| Afatinib 30mg and Docetaxel 60mg | 207.1 |
| Afatinib 30mg and Docetaxel 75mg | 233.6 |
| Afatinib 40mg and Docetaxel 75mg | 158.7 |
| Afatinib 50mg and Docetaxel 75mg | 85.0 |
Duration of Objective Response According to RECIST v1.1
Duration of objective response was the time from the first documented complete response or partial response to disease progression or death. (NCT01251653)
Timeframe: From the first documented complete response or partial response to the time of disease progression or death
| Intervention | Days (Mean) |
|---|
| Afatinib 30mg and Gemcitabine 1250mg | 291.0 |
| Afatinib 40mg and Gemcitabine 1000mg | 138.3 |
| Afatinib 30mg and Docetaxel 60mg | 410.0 |
| Afatinib 30mg and Docetaxel 75mg | 296.0 |
| Afatinib 40mg and Docetaxel 75mg | 55.5 |
Cmax of Docetaxel
Maximum concentration of docetaxel in plasma. (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55
| Intervention | ng/mL (Geometric Mean) |
|---|
| Docetaxel 60mg With Afatinib 30mg | 1690.0 |
| Docetaxel 60mg Without Afatinib | 1860.0 |
| Docetaxel 75mg With Afatinib 30mg | 1790.0 |
| Docetaxel 75mg Without Afatinib | 2080.0 |
Objective Response According to RECIST v1.1
Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. (NCT01251653)
Timeframe: From first drug administration until 28 days after last drug administration, up to 717 days.
| Intervention | Participants (Number) |
|---|
| No | Yes | Missing |
|---|
| Afatinib 30mg and Docetaxel 60mg | 17 | 1 | 0 |
,| Afatinib 30mg and Docetaxel 75mg | 12 | 5 | 1 |
,| Afatinib 30mg and Gemcitabine 1000mg | 3 | 0 | 0 |
,| Afatinib 30mg and Gemcitabine 1250mg | 6 | 1 | 1 |
,| Afatinib 40mg and Docetaxel 75mg | 7 | 4 | 1 |
,| Afatinib 40mg and Gemcitabine 1000mg | 15 | 4 | 1 |
,| Afatinib 40mg and Gemcitabine 1250mg | 6 | 0 | 0 |
,| Afatinib 50mg and Docetaxel 75mg | 6 | 0 | 0 |
,| Afatinib 50mg and Gemcitabine 1250mg | 2 | 0 | 0 |
AUC 0-24 of Docetaxel
Area under the concentration-time curve of docetaxel in plasma over the time interval from 0 up to 24 hours (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Docetaxel 60mg With Afatinib 30mg | 2000.0 |
| Docetaxel 60mg Without Afatinib | 2210.0 |
| Docetaxel 75mg With Afatinib 30mg | 2400.0 |
| Docetaxel 75mg Without Afatinib | 2270.0 |
Cmax,ss of Afatinib
Maximum concentration of Afatinib in plasma at steady state. (NCT01251653)
Timeframe: PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55
| Intervention | ng/mL (Geometric Mean) |
|---|
| Afatinib 40mg With Gemcitabine 1000 mg | 58.1 |
| Afatinib 40mg Without Gemcitabine | 66.4 |
| Afatinib 30mg With Docetaxel 60mg | 33.9 |
| Afatinib 30mg Without Docetaxel 60mg | 45.6 |
| Afatinib 30mg With Docetaxel 75mg | 33.9 |
| Afatinib 30mg Without Docetaxel 75mg | 45.7 |
The Incidence and Intensity of AEs With Grading According to CTCAE.
The incidence and intensity of adverse events with grading according to CTCAE. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE). (NCT01251653)
Timeframe: From first drug administration until 28 days after last drug administration, up to 717 days.
| Intervention | Participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Afatinib 30mg and Docetaxel 60mg | 1 | 3 | 6 | 6 | 2 |
,| Afatinib 30mg and Docetaxel 75mg | 0 | 1 | 4 | 11 | 2 |
,| Afatinib 30mg and Gemcitabine 1000mg | 0 | 2 | 0 | 0 | 1 |
,| Afatinib 30mg and Gemcitabine 1250mg | 0 | 1 | 6 | 1 | 0 |
,| Afatinib 40mg and Docetaxel 75mg | 0 | 0 | 4 | 6 | 2 |
,| Afatinib 40mg and Gemcitabine 1000mg | 0 | 5 | 6 | 5 | 4 |
,| Afatinib 40mg and Gemcitabine 1250mg | 0 | 2 | 2 | 1 | 1 |
,| Afatinib 50mg and Docetaxel 75mg | 0 | 1 | 2 | 1 | 2 |
,| Afatinib 50mg and Gemcitabine 1250mg | 0 | 0 | 1 | 1 | 0 |
Time to Objective Response According to RECIST v1.1
Objective response according to RECIST v1.1. Objective response is complete response or partial response for patients with measurable disease. Time to objective response is the time from the start of treatment to the date of first documented complete response or partial response. Descriptive analyses has been performed for the time to objective response (N(%) of patients with first occurrence of objective response at 6, 12 and 24 weeks). Onset of objective response is derived for patient with measurable disease. (NCT01251653)
Timeframe: 6 weeks, 12 weeks and 24 weeks
| Intervention | Participants (Number) |
|---|
| 6 Weeks | 12 Weeks | 24 Weeks | Not applicable |
|---|
| Afatinib 30mg and Docetaxel 60mg | 1 | 0 | 0 | 17 |
,| Afatinib 30mg and Docetaxel 75mg | 4 | 1 | 0 | 13 |
,| Afatinib 30mg and Gemcitabine 1000mg | 0 | 0 | 0 | 3 |
,| Afatinib 30mg and Gemcitabine 1250mg | 0 | 1 | 0 | 7 |
,| Afatinib 40mg and Docetaxel 75mg | 1 | 2 | 1 | 8 |
,| Afatinib 40mg and Gemcitabine 1000mg | 1 | 3 | 0 | 16 |
,| Afatinib 40mg and Gemcitabine 1250mg | 0 | 0 | 0 | 6 |
,| Afatinib 50mg and Docetaxel 75mg | 0 | 0 | 0 | 6 |
,| Afatinib 50mg and Gemcitabine 1250mg | 0 | 0 | 0 | 2 |
Disease Control According to RECIST v1.1
Disease control according to RECIST v1.1 Disease control is complete response, partial response or stable disease for measurable patients and complete response or non-CR/non-PD for non-measurable patients. Missing categories signify that no tumour imaging has been performed post baseline, and therefore the response status could not be assessed. (NCT01251653)
Timeframe: From first drug administration until 28 days after last drug administration, up to 717 days.
| Intervention | Participants (Number) |
|---|
| No | Yes | Missing |
|---|
| Afatinib 30mg and Docetaxel 60mg | 8 | 10 | 0 |
,| Afatinib 30mg and Docetaxel 75mg | 4 | 13 | 1 |
,| Afatinib 30mg and Gemcitabine 1000mg | 1 | 2 | 0 |
,| Afatinib 30mg and Gemcitabine 1250mg | 3 | 4 | 1 |
,| Afatinib 40mg and Docetaxel 75mg | 2 | 9 | 1 |
,| Afatinib 40mg and Gemcitabine 1000mg | 6 | 13 | 1 |
,| Afatinib 40mg and Gemcitabine 1250mg | 1 | 5 | 0 |
,| Afatinib 50mg and Docetaxel 75mg | 4 | 2 | 0 |
,| Afatinib 50mg and Gemcitabine 1250mg | 2 | 0 | 0 |
Overall Survival (OS)
Overall survival was defined as the time from the first administration of study medication to the time of death from any cause. (NCT01251653)
Timeframe: From the first administration of study medication to the time of death
| Intervention | Weeks (Median) |
|---|
| Afatinib 40mg and Gemcitabine 1000mg | 52.4 |
| Afatinib 30mg and Docetaxel 60mg | 38.4 |
| Afatinib 30mg and Docetaxel 75mg | NA |
Area Under the Concentration-time Curve (AUC) Tau,ss of Afatinib
Area under the concentration-time curve of Afatinib in plasma over a uniform dosing interval t at steady state. (NCT01251653)
Timeframe: PK samples were taken at hours; 167:55, 479:55, 481:05, 482:05, 483:05, 485:05, 487:05 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Afatinib 40mg With Gemcitabine 1000 mg | 1000.0 |
| Afatinib 40mg Without Gemcitabine | 1230.0 |
| Afatinib 30mg With Docetaxel 60mg | 642.0 |
| Afatinib 30mg Without Docetaxel 60mg | 746.0 |
| Afatinib 30mg With Docetaxel 75mg | 557.0 |
| Afatinib 30mg Without Docetaxel 75mg | 723.0 |
Progression Free Survival (PFS)
Progression-free survival was defined as the time from the first administration of study medication to the time of disease progression or death, whichever occurred first. (NCT01251653)
Timeframe: From the first administration of study medication to the time of disease progression or death
| Intervention | Weeks (Median) |
|---|
| Afatinib 40mg and Gemcitabine 1000mg | 23.9 |
| Afatinib 30mg and Docetaxel 60mg | 18.1 |
| Afatinib 30mg and Docetaxel 75mg | 23.6 |
Total Clearance (CL) of Gemcitabine
Total Clearance (CL) of Gemcitabine from plasma. (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3
| Intervention | mL/min (Geometric Mean) |
|---|
| Gemcitabine 1000mg With Afatinib 40 mg | 3020.0 |
| Gemcitabine 1000mg Without Afatinib | 4090.0 |
Volume of Distribution at Steady State (Vss) of Docetaxel
Apparent volume of distribution at steady state (Vss) of Docetaxel. (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 1, 2, 3, 5, 7, 23:55 and on day 22 at hours; -0:10, 1, 2, 3, 5, 7, 23:55
| Intervention | L (Geometric Mean) |
|---|
| Docetaxel 60mg With Afatinib 30mg | 255.0 |
| Docetaxel 60mg Without Afatinib | 315.0 |
| Docetaxel 75mg With Afatinib 30mg | 323.0 |
| Docetaxel 75mg Without Afatinib | 300.0 |
AUC 0-tz of Gemcitabine
Area under the concentration-time curve of Gemcitabine in plasma over the time interval from 0 up to the last quantifiable data point (NCT01251653)
Timeframe: PK samples were taken on day 1 at hours; -0:05, 0:30, 1, 1:30, 2, 3 and on day 22 at hours; -0:10, 0:30, 1, 1:30, 2, 3
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Gemcitabine 1000mg With Afatinib 40 mg | 9610.0 |
| Gemcitabine 1000mg Without Afatinib | 7120.0 |
Duration of Progression Free Survival After Initiation of Combination Phenelzine and Docetaxel Therapy
Progression free survival is calculated as the time from Day 1 of Combination therapy to first evidence of progression (by PSA, Measureable Disease, or Clinical Progression). For subjects who did not meet progression criteria, date of new therapy or date of death was used. Outcome is reported as mean. (NCT01253642)
Timeframe: Up to 6 years
| Intervention | days (Mean) |
|---|
| Combination Phenelzine and Docetaxel | 77.9 |
Response Rate in Measurable Disease by RECIST (Response Evaluation Criteria In Solid Tumors) Criteria
Response in measurable disease is defined as a 30% decrease in the sum of diameters of target lesions (as described by RECIST 1.1). (NCT01253642)
Timeframe: Up to 6 years
| Intervention | Participants (Count of Participants) |
|---|
| Combination Phenelzine and Docetaxel | 0 |
Time to Death From All Causes
Time to death is calculated from Day 1 of Combination therapy to death from any cause. (NCT01253642)
Timeframe: Up to 6 years
| Intervention | days (Median) |
|---|
| Combination Phenelzine and Docetaxel | 191.0 |
Toxicity of the Regimen
Number of participants who experienced an Adverse Event. Detail of Adverse Events is reported in the Adverse Event Section (NCT01253642)
Timeframe: Up to 6 years
| Intervention | Participants (Count of Participants) |
|---|
| Combination Phenelzine and Docetaxel | 11 |
Proportion of Patients Who Experience a PSA (Prostate-Specific Antigen) Decline of at Least 30%
PSA response: A ≥ 30% reduction from baseline within 12 weeks of initiation of therapy (confirmed on a second measurement at least 3 weeks later). (NCT01253642)
Timeframe: Within 12 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Combination Phenelzine and Docetaxel | 2 |
Maximum Change in PSA
Measured from Day 1 of Combination therapy to PSA at 12 Weeks on therapy (or earlier if subject not on therapy for 12 weeks). (NCT01253642)
Timeframe: 12 weeks (or earlier in patients who discontinued early)
| Intervention | percentage of PSA change (Median) |
|---|
| Combination Phenelzine and Docetaxel | 14.24 |
Frequency of MAOA (Monoamine Oxidase A) Overexpression in CRPC (Castration-Resistant Prostate Cancer) Tumors That Are Progressing on Docetaxel
Reported as Number of participants with MAOA expression greater than 5%. (NCT01253642)
Timeframe: Baseline
| Intervention | Participants (Count of Participants) |
|---|
| Combination Phenelzine and Docetaxel | 8 |
Half Life (t 1/2) of Ramucirumab
(NCT01256567)
Timeframe: Day 1 of Cycles 1 and 4 (cycle=21 days)
| Intervention | days (Geometric Mean) |
|---|
| t1/2 at Cycle 1 | t1/2 at Cycle 4 (n=6) |
|---|
| Ramucirumab and Docetaxel Combination | 6.57 | 11.9 |
Maximum Concentration (Cmax) of Ramucirumab
Cmax (Cycle 1) and Cmax at steady state (Cmax,ss, Cycle 4) of ramucirumab are provided. (NCT01256567)
Timeframe: Day 1 of Cycle 1 and Cycle 4 (cycle=21 days)
| Intervention | micrograms per milliliter (mcg/mL) (Geometric Mean) |
|---|
| Cmax at Cycle 1 | Cmax,ss at Cycle 4 (n=6) |
|---|
| Ramucirumab and Docetaxel Combination | 261 | 335 |
Number of Participants With Adverse Events
Number participants with drug related dose-limiting toxicities (DLT) during Cycle 1; ramucirumab related: treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or higher TEAE, or TEAE leading to discontinuation or ramucirumab dose modification. DLT=G4 neutropenia >7days; G ≥3 neutropenia with fever ≥38.5°C requiring IV antibiotics or bacteriemia or sepsis; G4 thrombocytopenia; G ≥3 thrombocytopenia with bleeding requiring platelets; G≥3 prothrombin time and/or partial thromboplastin time in absence of anticoagulants; G≥2 hyperbilirubinemia ≥5 days; QTc >500 milliseconds (ms) or increase ≥100 ms or arrhythmia; G≥4 or uncontrollable hypertension; G≥3 nonhematologic toxicity (excluding G3: hypersensitivity, injection-site reaction, arthralgia/myalgia, asthenia/fatigue, diarrhea without loperamide therapy, nausea/vomiting without antiemetics, transient G3/4 elevation of aminotransferases); treatment delay >2 weeks due to toxicity. (NCT01256567)
Timeframe: Baseline up to data cut off (approximately 48.3 weeks)
| Intervention | participants (Number) |
|---|
| Dose Limiting Toxicity (DLT) during Cycle 1 | TEAE related to ramucirumab | SAE related to ramucirumab | TEAE of Grade ≥3 related to ramucirumab | TEAE resulting in ramucirumab discontinuation | TEAE with ramucirumab dose modification/delay |
|---|
| Ramucirumab and Docetaxel Combination | 2 | 7 | 4 | 6 | 3 | 5 |
Steady State Volume of Distribution (Vss) of Ramucirumab
(NCT01256567)
Timeframe: Day 1 of Cycle 1 and 4 (cycle=21 days)
| Intervention | liters (L) (Geometric Mean) |
|---|
| Vss at Cycle 1 | Vss at Cycle 4 (n=6) |
|---|
| Ramucirumab and Docetaxel Combination | 2.96 | 3.92 |
Serum Anti-IMC-1121B Antibody Assessment (Immunogenicity)
The number of participants with a positive anti-IMC-1121B titer at any point during the study. (NCT01256567)
Timeframe: Baseline up to data cut off (approximately 48.3 weeks)
| Intervention | participants (Number) |
|---|
| Ramucirumab and Docetaxel Combination | 0 |
Area Under the Curve (AUC) of Ramucirumab
AUC from time zero to infinity (AUC[0-inf], Cycle 1) and at steady state (AUC tau, Cycle 4) of ramucirumab are provided. (NCT01256567)
Timeframe: Day 1 of Cycles 1 and 4 (cycle=21 days)
| Intervention | micrograms*day/milliliter (mcg*day/mL) (Geometric Mean) |
|---|
| AUC(0-inf) at Cycle 1 | AUC tau at Cycle 4 (n=6) |
|---|
| Ramucirumab and Docetaxel Combination | 1700 | 2320 |
Clearance (Cl) of Ramucirumab
Clearance (Cycle 1) and at steady state (Clss, Cycle 4) of ramucirumab are provided. (NCT01256567)
Timeframe: Day 1 of Cycle 1 and Cycle 4 (cycle=21 days)
| Intervention | milliliters per hour (mL/hr) (Geometric Mean) |
|---|
| Clearance at Cycle 1 | Clearance at steady state (Clss) at Cycle 4 (n=6) |
|---|
| Ramucirumab and Docetaxel Combination | 13.6 | 10.2 |
Toxicity Assessed by Adverse Events
Percentage of patients who ever experienced grade 2 or higher toxicites. (NCT01275677)
Timeframe: While on study therapy. Day 1 of first dose through 30 days after Day 1 of last dose.
| Intervention | percentage of patients (Number) |
|---|
| Arm I (Chemotherapy) | 90.9 |
| Arm II (Chemotherapy, Trastuzumab) | 94.1 |
Percentage of Patients Alive and Recurrence-Free (RFI)
Percentage of patients free from a recurrence-free interval event where events include invasive local, regional, or distant recurrence, or death from breast cancer (censored for death from other causes). (NCT01275677)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Arm I (Chemotherapy) | 92.3 |
| Arm II (Chemotherapy, Trastuzumab) | 92.0 |
Percentage of Patients Alive and Free From Invasive Disease (IDFS)
Percentage of patients free from an invasive disease-free survival event where events include any invasive recurrence, contralateral invasive breast cancer, second non-breast primary cancer (excluding squamous or basal cell carcinoma of the skin), or death from any cause. (NCT01275677)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Arm I (Chemotherapy) | 89.2 |
| Arm II (Chemotherapy, Trastuzumab) | 89.8 |
Percentage of Patients Alive and Free From Distant Recurrence (DRFI)
Percentage of patients free from a distant recurrence-free interval event where events include distant recurrence or death from breast cancer (censored for deaths from other causes), regardless of occurrence of any intervening local or regional recurrences, contralateral breast cancers, or non-breast second primary cancer. (NCT01275677)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Arm I (Chemotherapy) | 93.6 |
| Arm II (Chemotherapy, Trastuzumab) | 92.7 |
Percentage of Patients Alive and Free From Breast Cancer (BCFS)
Percentage of patients free from a breast cancer-free survival event where events include local recurrence (invasive or DCIS), regional or distant recurrence, contralateral breast cancer (invasive or DCIS), or death from any cause. (NCT01275677)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Arm I (Chemotherapy) | 91.0 |
| Arm II (Chemotherapy, Trastuzumab) | 90.7 |
Percentage of Patients Alive and Disease-Free (DFS-DCIS)
Percentage of patients free from a disease-free survival event where events include local recurrence (invasive or DCIS), regional or distant recurrence, contralateral breast cancer (invasive or DCIS), second primary cancer (excluding squamous or basal cell carcinoma of the skin), or death from any cause. (NCT01275677)
Timeframe: 5 years
| Intervention | percentage of patients (Number) |
|---|
| Arm I (Chemotherapy) | 89.1 |
| Arm II (Chemotherapy, Trastuzumab) | 89.6 |
Percentage of Patients Alive (Overall Survival)
Percentage of patients alive. (NCT01275677)
Timeframe: 5 years
| Intervention | percentage of patients alive (Number) |
|---|
| Arm I (Chemotherapy) | 96.3 |
| Arm II (Chemotherapy, Trastuzumab) | 94.8 |
Duration of Response
The duration of response was measured from the time measurement criteria were first met for a CR or PR (whichever was first recorded) until the first date of objectively documented progressive disease (taking as a reference for progressive disease the smallest measurement recorded since randomization) or the date of death, whichever occurred first. Data for participants who did not relapse or die were censored at the day of their last adequate tumor assessment. Duration of response was estimated by the Kaplan-Meier method. (NCT01282463)
Timeframe: First Criteria Met for CR or PR to Measured PD or Death From Any Cause (Up to 40 Months)
| Intervention | months (Median) |
|---|
| Docetaxel | 4.6 |
| Docetaxel + Ramucirumab DP | 4.6 |
| Docetaxel + Icrucumab | NA |
Number of Participants With Serum Anti-Ramucirumab Antibody Assessment
Number of participants with at least one positive titer treatment emergent antibody positive neutralizing antibody detecting. A sample will be considered positive for anti-Ramucirumab antibodies if it exhibits a post-baseline antibody level exceeding the normal anti-Ramucirumab antibody level seen in healthy untreated individuals. (NCT01282463)
Timeframe: Cycle 1:Predose,EOI,1hr,48hr,72hr,168hr,336 hr post-EOI:Cycle 2:Predose,1hr post-EOI;Cycle 3:Predose,1hr,48hr,72hr,168hr,336hr post-EOI;Cycle 4:Predose,1hr post-EOI;Cycle 6:Predose,1hr post-EOI
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel + Ramucirumab DP | 1 |
Percentage of Participants Achieving Objective Response Rate (ORR)
Participants achieved an objective response if they had a best overall response of partial response (PR) or complete response (CR). According to RECIST v1.1, PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter; CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels [if tumor markers were initially above the upper limit of normal (ULN)]. The percentage of participants who achieved an objective response=(number of participants with CR or PR)/(number of participants assessed)*100. (NCT01282463)
Timeframe: Randomization to Measured PD (Up to 40 Months)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel | 8.9 |
| Docetaxel + Ramucirumab DP | 23.9 |
| Docetaxel + Icrucumab | 12.2 |
Pharmacokinetics (PK) Maximum Concentration (Cmax) Ramucirumab
(NCT01282463)
Timeframe: Cycle 1:Predose,1 hour(hr) post End of Infusion (EOI),48hr,72hr,168hr,336hr post-EOI;Cycle2:Predose,1hr post-EOI; Cycle3:Predose,1hr,48hr,72hr,168hr,336hr post-EOI; Cycle4:Predose,1hr post-EOI;Cycle6 and every other cycle thereafter:Predose,1hr Post EOI
| Intervention | microgram/milliliter (ug/mL) (Geometric Mean) |
|---|
| Cycle 1 | Cycle 2 | Cycle 3 | Cycle 4 | Cycle 6 |
|---|
| Docetaxel + Ramucirumab DP | 258 | 304 | 300 | 279 | 252 |
Number of Participants With Adverse Events (AEs)
A summary of other nonserious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section. (NCT01282463)
Timeframe: Up To 41.7 Months
| Intervention | Participants (Count of Participants) |
|---|
| Any AE | Any SAE |
|---|
| Docetaxel | 45 | 19 |
,| Docetaxel + Icrucumab | 49 | 22 |
,| Docetaxel + Ramucirumab DP | 46 | 25 |
Progression-Free Survival (PFS)
PFS time was the time from randomization until the date of objectively determined progressive disease (PD) or death due to any cause, whichever occurred first. According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), PD was 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 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD who were alive at the end of the follow-up period (or lost to follow-up) were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization. (NCT01282463)
Timeframe: Randomization to Measured PD or Death From Any Cause (Up To 40 Months)
| Intervention | months (Median) |
|---|
| Docetaxel | 2.8 |
| Docetaxel + Ramucirumab DP | 5.4 |
| Docetaxel + Icrucumab | 1.6 |
PK: Minimum Concentration (Cmin) Ramucirumab
(NCT01282463)
Timeframe: Cycle 2:Predose,1hr post-EOI;Cycle3:Predose,1hr,48hr,72hr,168hr,336hr, post-EOI;Cycle4:Predose,1hr post-EOI;Cycle6:Predose,1hr Post EOI
| Intervention | microgram/milliliter (ug/mL) (Geometric Mean) |
|---|
| Cycle 2 | Cycle 3 | Cycle 4 | Cycle 6 |
|---|
| Docetaxel + Ramucirumab DP | 19.5 | 39.9 | 35.3 | 31.2 |
PK: Cmin Icrucumab
(NCT01282463)
Timeframe: Cycle 2:Predose,1hr post-EOI;Cycle 3:Predose,EOI,1.5hr,24hr,48hr,72hr,168hr Post EOI
| Intervention | ug/mL (Geometric Mean) |
|---|
| Day 1 Cycle 2 | Day 1 Cycle 3 |
|---|
| Docetaxel + Icrucumab | NA | 153 |
PK: Cmax Icrucumab
(NCT01282463)
Timeframe: Cycle 1:Predose,1 hr post-EOI, 48hr, 72hr Post-EOI; Cycle 3:Predose,EOI,1.5hr,24hr,48hr,72hr,168hr Post EOI
| Intervention | ug/mL (Geometric Mean) |
|---|
| Cycle 1 Cmax | Cycle 3 Cmax |
|---|
| Docetaxel + Icrucumab | 474 | 599 |
Number of Participants With a Clinically Significant Effects
Clinically significant effects are reported if a Grade 3 or higher treatment emergent adverse event (TEAE) and observed in ≥10% of participants or a toxicity possibly related to study drug based on Common Terminology Criteria for Adverse Events (CTCAE). A summary of other nonserious AEs and all SAEs, regardless of causality is located in the Reported Adverse Event section. (NCT01284335)
Timeframe: Baseline to Study Completion (Up to 2 years)
| Intervention | Participants (Count of Participants) |
|---|
| TEAE >/= Grade 3 | Toxicity >/= Grade 3 |
|---|
| Arm A Tasisulam + Gemcitabine Dose Confirmation | 18 | 18 |
,| Arm A Tasisulam + Gemcitabine Dose Escalation | 15 | 13 |
,| Arm B* Tasisulam + Docetaxel Dose Escalation | 0 | 4 |
,| Arm B1 Tasisulam + Docetaxel Dose Escalation | 0 | 5 |
,| Arm B2 Tasisulam + Docetaxel Dose Confirmation | 19 | 26 |
,| Arm B2 Tasisulam + Docetaxel Dose Escalation | 16 | 18 |
,| Arm C Tasisulam + Temozolomide Dose Confirmation | 6 | 6 |
,| Arm C Tasisulam + Temozolomide Dose Escalation | 11 | 13 |
,| Arm D Tasisulam + Cisplatin Dose Confirmation | 30 | 30 |
,| Arm D Tasisulam + Cisplatin Dose Escalation | 8 | 7 |
,| Arm D* Tasisulam + Cisplatin Dose Escalation | 0 | 1 |
,| Arm E Tasisulam + Erlotinib Dose Confirmation | 7 | 7 |
,| Arm E Tasisulam + Erlotinib Dose Escalation | 5 | 5 |
Number of Participants With Dose-Limiting Toxicities Cycle 1
A Dose-Limiting Toxicity (DLT) is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfills any one of the following criteria: Common Terminology Criteria for Adverse Events (CTCAE, Version 3.0) Grade 4 neutropenia lasting more than 5 days. Grade 4 neutropenia with fever or Grade 4 thrombocytopenia, regardless of duration; Grade ≥3 thrombocytopenia with bleeding, regardless of duration; Grade ≥3 nonhematologic toxicity (excluding nausea/vomiting or diarrhea that can be controlled with medication, and alopecia). Grade 3 electrolyte toxicity (for example, hypokalemia, hypophosphatemia) will not be considered a DLT unless it is considered related to the study drug or combination and does not resolve with standard replacement treatments within 42 days after Cycle 1 Day 1. A summary of other nonserious AEs and all Serious Adverse Events (SAE), regardless of causality is located in the Reported Adverse Event section. (NCT01284335)
Timeframe: Baseline to Cycle 1 (Up to Day 28)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A Tasisulam + Gemcitabine Dose Escalation | 4 |
| Arm A Tasisulam + Gemcitabine Dose Confirmation | 0 |
| Arm B* Tasisulam + Docetaxel Dose Escalation | 4 |
| Arm B1 Tasisulam + Docetaxel Dose Escalation | 4 |
| Arm B2 Tasisulam + Docetaxel Dose Escalation | 3 |
| Arm B2 Tasisulam + Docetaxel Dose Confirmation | 0 |
| Arm C Tasisulam + Temozolomide Dose Escalation | 3 |
| Arm C Tasisulam + Temozolomide Dose Confirmation | 0 |
| Arm D* Tasisulam + Cisplatin Dose Escalation | 0 |
| Arm D Tasisulam + Cisplatin Dose Escalation | 2 |
| Arm D Tasisulam + Cisplatin Dose Confirmation | 0 |
| Arm E Tasisulam + Erlotinib Dose Escalation | 1 |
| Arm E Tasisulam + Erlotinib Dose Confirmation | 0 |
PK: Area Under the Curve Albumin (AUCalb)
Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion. (NCT01284335)
Timeframe: Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
| Intervention | micrograms*hour/milliliter (µg*h/mL) (Geometric Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| Tasisulam | 946 | 648 |
Pharmacokinetic (PK): Concentration Maximum (Cmax)
Cycle 2: predose,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion. (NCT01284335)
Timeframe: Cycle 1: predose,0,30min,1h start of infusion, end of infusion, 30min,2h,4h,6h,22h,166h,334h,698h end of infusion.
| Intervention | micrograms per milliliter (µg/mL) (Geometric Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| Tasisulam | 306 | 250 |
Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response)
Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 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. (NCT01284335)
Timeframe: Baseline to Study Completion (Up to 2 years)
| Intervention | percentage of participants (Number) |
|---|
| Non-Small Cell Lung Cancer (NSCLC) | Other | Pancreas | Small Cell Lung Cancer (SCLC) |
|---|
| Arm D Tasisulam + Cisplatin Dose Confirmation | 5.0 | 10.0 | 0 | 7.1 |
Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response)
Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 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. (NCT01284335)
Timeframe: Baseline to Study Completion (Up to 2 years)
| Intervention | percentage of participants (Number) |
|---|
| Non-Small Cell Lung Cancer (NSCLC) | Other | Pancreas |
|---|
| Arm A Tasisulam + Gemcitabine Dose Confirmation | 0.0 | 14.3 | 13.3 |
,| Arm E Tasisulam + Erlotinib Dose Confirmation | 0.0 | 14.3 | 0.0 |
Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response)
Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 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. (NCT01284335)
Timeframe: Baseline to Study Completion (Up to 2 years)
| Intervention | percentage of participants (Number) |
|---|
| Non-Small Cell Lung Cancer (NSCLC) | Other |
|---|
| Arm B* Tasisulam + Docetaxel Dose Confirmation | 20.0 | 6.3 |
Percentage of Participants With a Complete (CR) or Partial Response (PR) (Best Overall Tumor Response)
Best overall tumor response was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST, version 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. (NCT01284335)
Timeframe: Baseline to Study Completion (Up to 2 years)
| Intervention | percentage of participants (Number) |
|---|
| Other |
|---|
| Arm C Tasisulam + Temozolomide Dose Confirmation | 0.0 |
Incidence of Grade 3 and 4 Toxicities by Arm
Measure the grade III/IV toxicities experienced by patients with advanced, locally recurrent, or metastatic SCCHN (NCT01285635)
Timeframe: 3 years
| Intervention | participants (Number) |
|---|
| Fatigue | Anorexia | Nausea | Bowel Obstruction | Hematologic | Infectious | Respiratory | Edema | Other |
|---|
| Docetaxel Then Metronomic AT-101 | 2 | 1 | 1 | 1 | 14 | 4 | 1 | 0 | 1 |
,| Metronomic AT-101 Arm | 0 | 1 | 0 | 1 | 4 | 1 | 3 | 1 | 1 |
,| Pulse AT-101 Then Metronomic AT-101 | 1 | 2 | 5 | 0 | 8 | 0 | 0 | 2 | 2 |
Number of Patients With a Complete Response (CR) and Partial Response (PR)
The primary objective is to estimate the proportion of patients with a complete response (CR) and partial response(PR) defined by RECIST (Response Evaluation Criteria in Solid Tumors). CR is defined as the disappearance of all target lesions and PR is defined as at least a 20% decrease in the sum of the longest diameter of target lesions. (NCT01285635)
Timeframe: 12 months
| Intervention | Patients (Number) |
|---|
| Number of Patients with a CR | Number of Patients with a PR |
|---|
| Docetaxel Then Metronomic AT-101 | 0 | 1 |
,| Metronomic AT-101 Arm | 0 | 2 |
,| Pulse AT-101 Then Metronomic AT-101 | 0 | 1 |
Clinical Benefit Rate
Clinical benefit rate was assessed according to RECIST 1.0 and defined as the percentage of participants who experienced a CR, PR, or stable disease (SD) for at least 6 months. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. SD was defined as small changes that do not meet above criteria. (NCT01301729)
Timeframe: up to 28 months
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab | 81.3 |
Duration of Response
Duration of response was defined as the time from when a PR or CR was first documented until the date of documented PD or death. CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. PD was defined as 20% increase in the sum of the longest diameter of target lesions. (NCT01301729)
Timeframe: From the time of PR or CR until the date of PD or death (up to 28 months)
| Intervention | months (Median) |
|---|
| Trastuzumab | 9.8 |
Overall Response Rate
Overall response rate was assessed using RECIST 1.0 and defined as the percentage of participants that achieved a complete response (CR) or a partial response (PR). CR was defined as complete disappearance of all target and non-target lesions and no new lesions. PR was defined as greater than or equal to (≥) 30 % decrease in the sum of appropriate diameters of all target measurable lesions, no progress in the non-measurable disease, and no new lesions. (NCT01301729)
Timeframe: up to 28 months
| Intervention | percentage of participants (Number) |
|---|
| Tastuzumab | 81.3 |
Overall Survival
Overall survival was defined as the time from the date of enrollment to the date of death due to any cause. (NCT01301729)
Timeframe: Time from enrollment to the date of death (up to 28 months)
| Intervention | months (Median) |
|---|
| Trastuzumab | NA |
Percentage of Participants With an Adverse Event (AE)
An AE was defined as any adverse medical event that occurred after the participant used the investigational medicinal product (IMP) or other intervention behaviors specified by the protocol in the clinical trial regardless of relationship to the study treatment. (NCT01301729)
Timeframe: Up to 28 days after last infusion of the study drug (28 months)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab | 93.8 |
Time to Progression
Time to progression was defined as the time from the date of enrollment until the date of progressive disease. (NCT01301729)
Timeframe: From the date of enrollment until the date of progressive disease (up to 28 months)
| Intervention | months (Median) |
|---|
| Trastuzumab | 9.9 |
Progression-Free Survival (PFS)
PFS was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.0 and was defined as the time from the date when the participant signed the informed consent form (ICF) until death or progressive disease (PD). PD was defined as 20% increase in the sum of the longest diameter of target lesions. PFS and associated confidence intervals were calculated using the Kaplan-Meier method. (NCT01301729)
Timeframe: From the date of informed consent to the date of death or progressive disease (up to 28 months)
| Intervention | months (Median) |
|---|
| Trastuzumab | 9.9 |
Time to Tumor Progression Free Survival
Time to tumor progression free survival was defined as the time interval between randomization and the date of first occurrence of tumor progression (assessed using RECIST version 1.1) or death, whichever was earlier. Analysis was performed by Kaplan-Meier method. (NCT01308567)
Timeframe: Baseline up to tumor progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
| Intervention | months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 12.1 |
| Cabazitaxel 20 mg/m^2 | 13.4 |
| Cabazitaxel 25 mg/m^2 | 13.1 |
Overall Survival (OS)
OS was defined as the time interval from the date of randomization to the date of death due to any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive, or at the cut-off date if the participant's last contact was after the cut-off date. The study cut-off date for the final analysis of OS was the date when the 774th death had been observed. Analysis was performed by Kaplan-Meier method. (NCT01308567)
Timeframe: Baseline up to death or study cut-off date, whichever was earlier (maximum duration: 51 months )
| Intervention | months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 24.3 |
| Cabazitaxel 20 mg/m^2 | 24.5 |
| Cabazitaxel 25 mg/m^2 | 25.2 |
Time to Prostate Serum Antigen Progression Free Survival (PSA-PFS)
Time to PSA-PFS: time interval between date of randomization & first occurrence of PSA progression/ death, whichever was earlier. PSA progression:1) In PSA responders(≥50% decline from baseline PSA of ≥10 ng/mL):increase of ≥25%(at least 2 ng/mL)over nadir value, confirmed by second PSA value at least 3 weeks later;2)In PSA non-responders(not achieved ≥50% decline from baseline PSA ≥10 ng/mL):increase of ≥25% (at least 2 ng/mL) over baseline value, confirmed by second PSA value at least 3 weeks later;3)In participants not eligible for PSA response(baseline PSA <10 ng/mL):(a)in participants with baseline PSA>0 ng/mL&<10 ng/mL: increase in PSA by 25% (at least 2 ng/mL) above baseline level, confirmed by second PSA value at least 3weeks apart;(b)in participants with baseline value=0ng/mL: a post baseline PSA value ≥2ng/mL.Early rise in PSA only indicated progression if it was associated with another sign of DP or if it continued beyond 12 weeks. Analysis performed by Kaplan-Meier method. (NCT01308567)
Timeframe: Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
| Intervention | months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 8.3 |
| Cabazitaxel 20 mg/m^2 | 8.2 |
| Cabazitaxel 25 mg/m^2 | 9.2 |
Change From Baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P):Trial Outcome Index (TOI) as a Measure of HRQoL
FACT-P was a 39-item participant rated questionnaire that measures the concerns of participants with prostate cancer. It consisted of 5 sub-scales assessing physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and prostate-specific concerns (12 items). Physical well being, functional well being, and prostate-specific concerns sub-scales of the FACT-P questionnaire were combined to calculate TOI. Total TOI score ranges from 0 to 104, with higher scores representing a better quality of life with fewer symptoms. (NCT01308567)
Timeframe: Baseline, Day 1 of each cycle 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 (each cycle 21-day); post-treatment follow up 1, 2, 3, 4, 5, 6 (each up to 12 weeks)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Change at Cycle 1 | Change at Cycle 2 | Change at Cycle 3 | Change at Cycle 4 | Change at Cycle 5 | Change at Cycle 6 | Change at Cycle 7 | Change at Cycle 8 | Change at Cycle 9 | Change at Cycle 10 | Change at Cycle 11 | Change at Cycle 12 | Change at Cycle 13 | Change at Cycle 14 | Change at Cycle 15 | Change at Cycle 16 | Change at Follow-up 1 | Change at Follow-up 2 | Change at Follow-up 3 | Change at Follow-up 4 | Change at Follow-up 5 | Change at Follow-up 6 |
|---|
| Cabazitaxel 20 mg/m^2 | 6.09 | 5.96 | 5.28 | 4.1 | 4.05 | 3.15 | 3.14 | 2.26 | 2.15 | 1.56 | 2.72 | 3.08 | 1.78 | 1.59 | 1.29 | 1.23 | -1.26 | -1.12 | -1.67 | -2.54 | -5.36 | -5.32 |
,| Cabazitaxel 25 mg/m^2 | 5.76 | 4.26 | 3.65 | 3.2 | 3.1 | 2.88 | 2.94 | 1.49 | 1.73 | 1.62 | 2.19 | 0.75 | 0.82 | -0.07 | 1.49 | 1.44 | -1.62 | -1.05 | -1.98 | -1.03 | -0.82 | -2.76 |
,| Docetaxel 75 mg/m^2 | 3.31 | 4.37 | 4.31 | 3.39 | 3.41 | 2.76 | 2.29 | 1.67 | 1.75 | 1.52 | 0.35 | 1.04 | 2.13 | -0.13 | -2.1 | -2.26 | -0.96 | -0.07 | -0.32 | -0.91 | -2.15 | -1.77 |
Percentage of Participants With Overall Objective Tumor Response
Overall objective tumor response was defined as having a partial response (PR) or complete response (CR) according to the RECIST version 1.1. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker level. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <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. (NCT01308567)
Timeframe: Baseline up to DP or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel 75 mg/m^2 | 30.9 |
| Cabazitaxel 20 mg/m^2 | 32.4 |
| Cabazitaxel 25 mg/m^2 | 41.6 |
Time to Pain Progression Free Survival (Pain PFS)
Time to pain PFS was defined as the time interval between date of randomization and the date of the first occurrence of pain progression or death, whichever was earlier. Pain progression was defined as an increase of ≥1 point in the median present pain intensity (PPI) score from the nadir confirmed by a second assessment at least 3 weeks later or ≥25 % increase in the mean analgesic score from baseline, due to cancer related pain confirmed by a second assessment at least 3 weeks later or requirement for local palliative radiotherapy. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. Analysis was performed by Kaplan-Meier method. (NCT01308567)
Timeframe: Baseline until disease progression, death or study cut-off date (maximum duration: 51 months)
| Intervention | months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 10.1 |
| Cabazitaxel 20 mg/m^2 | 8.0 |
| Cabazitaxel 25 mg/m^2 | 7.3 |
Progression Free Survival (PFS)
PFS: time interval between date of randomization to date of first occurrence of any of following events: tumor progression according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1; Prostate Specific Antigen (PSA) progression; pain progression or death due to any cause. Analysis was performed by Kaplan-Meier method. (NCT01308567)
Timeframe: Baseline up to tumor progression, PSA progression, pain progression or death (maximum duration: 51 months)
| Intervention | months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 5.3 |
| Cabazitaxel 20 mg/m^2 | 4.4 |
| Cabazitaxel 25 mg/m^2 | 5.1 |
Percentage of Participants With PSA Response
PSA response was defined as ≥50% decrease from baseline in serum PSA levels, confirmed by a second PSA value at least 3 weeks later in participants with baseline PSA value ≥10 ng/mL. (NCT01308567)
Timeframe: Baseline up to PSA progression or death due to any cause or study cut-off date, whichever was earlier (maximum duration: 51 months)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel 75 mg/m^2 | 68.4 |
| Cabazitaxel 20 mg/m^2 | 60.7 |
| Cabazitaxel 25 mg/m^2 | 68.7 |
Percentage of Participants With Pain Response
Pain response was defined as either a ≥2-point decrease from baseline median PPI score without increase in analgesic score, or a ≥50% decrease in analgesic use from baseline mean analgesic score (only in participants with baseline mean analgesic score≥10) without increase in the pain. Either criterion was maintained for 2 consecutive evaluations at least 3 weeks apart. PPI was rated by participant in a diary using a scale of 0=no pain, 1=mild, 2=discomforting, 3=distressing, 4=horrible 5=excruciating. Analgesic use was recorded by the participant in a diary. Analgesic score was calculated from the analgesic use data based on a table of analgesic medications, with non-narcotic medications assigned a value of 1 point and narcotic medications assigned a value of 4 points. (NCT01308567)
Timeframe: Baseline until pain progression, death or study cut-off date (maximum duration: 51 months)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel 75 mg/m^2 | 40.7 |
| Cabazitaxel 20 mg/m^2 | 42.4 |
| Cabazitaxel 25 mg/m^2 | 39.4 |
Time to Progression (TTP) According to RECIST v1.1
The time to progression was defined as the time from baseline until disease progression as determined by the RECIST v1.1. TTP2 is defined as the interval between the day of randomization at PD1 and PD2. TTP3 is defined as the interval between the day of PD2 and PD3. PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (NCT01351415)
Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)
| Intervention | Months (Median) |
|---|
| TTP2 | TTP3 |
|---|
| Bevacizumab + Standard of Care | 5.55 | 4.07 |
,| Standard of Care | 4.21 | 2.73 |
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study and laboratory or clinical tests that resulted in a change in treatment or discontinuation from study drug were reported as adverse events. A SAE was any experience that: resulted in death, was life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect or was medically significant. (NCT01351415)
Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)
| Intervention | Percentage of Participants (Number) |
|---|
| AEs | SAEs |
|---|
| Bevacizumab + Standard of Care | 97.5 | 51.9 |
,| Standard of Care | 96.1 | 37.1 |
Percentage of Participants Who Are Alive at Month 6, 12, and 18
Percentage of participants who were alive at Month 6, 12 and 18 were reported. (NCT01351415)
Timeframe: Month 6, 12, 18
| Intervention | Percentage of Participants (Number) |
|---|
| Month 6 | Month 12 | Month 18 |
|---|
| Bevacizumab + Standard of Care | 0.8 | 0.5 | 0.4 |
,| Standard of Care | 0.7 | 0.4 | 0.3 |
Percentage of Participants With Objective Response According to RECIST v1.1
The objective response is defined as complete response (CR) or partial response (PR) assessed according to the RECIST v.1.1 criteria with baseline tumour assessment as the reference. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. (NCT01351415)
Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Bevacizumab + Standard of Care | 8.6 |
| Standard of Care | 6.3 |
Percentage of Participants With Disease Control According to RECIST v1.1
The disease control rate is defined as CR or PR or stable disease (SD) assessed according to the RECIST v.1.1 criteria with baseline tumour assessment as the reference. SD was defined as neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of the longest diameter since treatment started for target lesions and the persistence of 1 or more non-target lesions. (NCT01351415)
Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Bevacizumab + Standard of Care | 80.2 |
| Standard of Care | 77.0 |
Overall Survival (OS)
Overall survival (OS) was defined as the time from the date of randomization at first progression of disease to the date of death, regardless of the cause of death. (NCT01351415)
Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)
| Intervention | Months (Median) |
|---|
| Bevacizumab + Standard of Care | 11.86 |
| Standard of Care | 10.22 |
Duration of Response (DoR) According to RECIST v1.1
Duration of response is defined as the time that measurement criteria are met for objective response (CR/PR) (whichever status is recorded first) until the first date of progression or death is documented. CR was defined as disappearance of all target and non-target lesions and (if applicable) normalization of tumor marker levels. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than < 10 mm. PR was defined as greater than or equal to ≥30 % decrease in sum of longest diameter of target lesions in reference to baseline sum longest diameter. (NCT01351415)
Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)
| Intervention | Months (Median) |
|---|
| Bevacizumab + Standard of Care | 7.46 |
| Standard of Care | 6.24 |
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
PFS was defined as the time from start of treatment to the first event of death or PD. Tumor response was assessed by the IRF according to RECIST v1.1. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-study sum LD, or the appearance of new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. PFS2 is defined as the time between randomization at PD1 and the date of PD2 or death, whichever occurs first. PFS3 is defined as the time between PD2 and the date of PD3 or death, whichever occurs first. (NCT01351415)
Timeframe: Up to data cut-off date 24 June 2016 (approximately 5 years)
| Intervention | Months (Median) |
|---|
| PFS 2 | PFS 3 |
|---|
| Bevacizumab + Standard of Care | 5.45 | 4.01 |
,| Standard of Care | 3.98 | 2.60 |
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
| Intervention | Estimate of percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 95.18 |
| Placebo + Trastuzumab + Chemotherapy | 94.27 |
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
| Intervention | percentage of participants (Number) |
|---|
| Baseline: No problems | Baseline: Some problems | Baseline: Unable | Week 13: No problems | Week 13: Some problems | Week 13: Unable | Week 25: No problems | Week 25: Some problems | Week 25: Unable | EOT: No problems | EOT: Some problems | EOT: Unable | FU Month 18: No problems | FU Month 18: Some problems | FU Month 18: Unable | FU Month 24: No problems | FU Month 24: Some problems | FU Month 24: Unable | FU Month 36: No problems | FU Month 36: Some problems | FU Month 36: Unable |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 67.4 | 30.4 | 2.2 | 56.8 | 40.1 | 3.1 | 66.5 | 32.2 | 1.2 | 72.4 | 26.3 | 1.3 | 78.5 | 20.6 | 0.9 | 78.7 | 20.4 | 0.9 | 80.9 | 18.3 | 0.7 |
,| Placebo + Trastuzumab + Chemotherapy | 66.1 | 32.2 | 1.7 | 54.1 | 43.0 | 2.9 | 65.8 | 32.7 | 1.4 | 72.5 | 26.6 | 0.9 | 76.3 | 23.0 | 0.7 | 79.1 | 19.7 | 1.1 | 79.8 | 19.4 | 0.8 |
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
| Intervention | percentage of participants (Number) |
|---|
| Baseline: No problems | Baseline: Some problems | Baseline: Confined to bed | Week 13: No problems | Week 13: Some problems | Week 13: Confined to bed | Week 25: No problems | Week 25: Some problems | Week 25: Confined to bed | EOT: No problems | EOT: Some problems | EOT: Confined to bed | FU Month 18: No problems | FU Month 18: Some problems | FU Month 18: Confined to bed | FU Month 24: No problems | FU Month 24: Some problems | FU Month 24: Confined to bed | FU Month 36: No problems | FU Month 36: Some problems | FU Month 36: Confined to bed |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 93.8 | 6.2 | 0.0 | 77.5 | 22.1 | 0.4 | 83.8 | 16.1 | 0.1 | 85.1 | 14.8 | 0.1 | 88.8 | 11.2 | 0.1 | 87.8 | 12.1 | 0.1 | 88.5 | 11.5 | 0.0 |
,| Placebo + Trastuzumab + Chemotherapy | 92.9 | 6.9 | 0.2 | 74.8 | 24.8 | 0.4 | 82.7 | 17.2 | 0.1 | 84.9 | 14.9 | 0.2 | 87.0 | 12.8 | 0.2 | 87.7 | 12.1 | 0.1 | 87.8 | 12.1 | 0.1 |
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
| Intervention | Estimate of percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 93.42 |
| Placebo + Trastuzumab + Chemotherapy | 92.29 |
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
| Intervention | Estimate of percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 95.70 |
| Placebo + Trastuzumab + Chemotherapy | 95.13 |
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
| Intervention | Estimate of percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 94.06 |
| Placebo + Trastuzumab + Chemotherapy | 93.24 |
Trough Serum Concentration (Cmin) of Pertuzumab
(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 | Cycle 10 | Cycle 15 |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 68.0 | 88.1 | 95.5 |
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
| Intervention | percentage of participants (Number) |
|---|
| Baseline: No pain/discomfort | Baseline: Moderate pain/discomfort | Baseline: Extreme pain/discomfort | Week 13: No pain/discomfort | Week 13: Moderate pain/discomfort | Week 13: Extreme pain/discomfort | Week 25: No pain/discomfort | Week 25: Moderate pain/discomfort | Week 25: Extreme pain/discomfort | EOT: No pain/discomfort | EOT: Moderate pain/discomfort | EOT: Extreme pain/discomfort | FU Month 18: No pain/discomfort | FU Month 18: Moderate pain/discomfort | FU Month 18: Extreme pain/discomfort | FU Month 24: No pain/discomfort | FU Month 24: Moderate pain/discomfort | FU Month 24: Extreme pain/discomfort | FU Month 36: No pain/discomfort | FU Month 36: Moderate pain/discomfort | FU Month 36: Extreme pain/discomfort |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 49.0 | 50.0 | 1.0 | 44.6 | 52.7 | 2.7 | 44.3 | 53.3 | 2.4 | 49.3 | 48.5 | 2.2 | 51.3 | 46.6 | 2.1 | 56.7 | 41.3 | 1.9 | 59.5 | 38.9 | 1.6 |
,| Placebo + Trastuzumab + Chemotherapy | 49.0 | 49.7 | 1.3 | 40.5 | 56.5 | 3.0 | 43.7 | 54.4 | 1.9 | 50.0 | 47.6 | 2.4 | 53.1 | 44.7 | 2.1 | 56.0 | 41.5 | 2.5 | 57.8 | 40.1 | 2.1 |
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
| Intervention | percentage of participants (Number) |
|---|
| Baseline: Not anxious/depress | Baseline: Moderate anxious/depress | Baseline: Extreme anxious/depress | Week 13: Not anxious/depress | Week 13: Moderate anxious/depress | Week 13: Extreme anxious/depress | Week 25: No anxious/depress | Week 25: Moderate anxious/depress | Week 25: Extreme anxious/depress | EOT: Not anxious/depress | EOT: Moderate anxious/depress | EOT: Extreme anxious/depress | FU Month 18: Not anxious/depress | FU Month 18: Moderate anxious/depress | FU Month 18: Extreme anxious/depress | FU Month 24: Not anxious/depress | FU Month 24: Moderate anxious/depress | FU Month 24: Extreme anxious/depress | FU Month 36: Not anxious/depress | FU Month 36: Moderate anxious/depress | FU Month 36: Extreme anxious/depress |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 47.1 | 49.4 | 3.5 | 53.6 | 43.4 | 3.0 | 55.5 | 41.9 | 2.5 | 58.5 | 38.9 | 2.6 | 61.4 | 36.2 | 2.4 | 63.8 | 33.8 | 2.4 | 64.0 | 33.3 | 2.6 |
,| Placebo + Trastuzumab + Chemotherapy | 44.7 | 50.1 | 5.2 | 52.4 | 44.0 | 3.7 | 55.5 | 41.8 | 2.7 | 58.3 | 39.1 | 2.6 | 59.9 | 37.0 | 3.1 | 61.0 | 36.2 | 2.8 | 61.6 | 35.4 | 3.0 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Primary Cardiac Event (Composite) | Heart Failure and LVEF Decline | Cardiac Death (Definite or Probable) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 0.7 | 0.6 | 0.1 |
,| Placebo + Trastuzumab + Chemotherapy | 0.3 | 0.2 | 0.1 |
Cmin of Trastuzumab
(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1 | Cycle 10 | Cycle 15 |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 32.1 | 65.0 | 72.9 |
,| Placebo + Trastuzumab + Chemotherapy | 34.1 | 68.4 | 71.0 |
Cmax of Trastuzumab
(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1 | Cycle 10 | Cycle 15 |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 180 | 219 | 187 |
,| Placebo + Trastuzumab + Chemotherapy | 190 | 225 | 234 |
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)
| Intervention | percentage of blood pumped out (Mean) |
|---|
| Baseline | Change to Worst Value |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 65.2 | -7.5 |
,| Placebo + Trastuzumab + Chemotherapy | 65.3 | -7.6 |
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
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change at Week 13 | Change at Week 25 | Change at EOT | Change at FU Month 18 | Change at FU Month 24 | Change at FU Month 36 |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 72.9 | -11.2 | -4.4 | -3.1 | 1.9 | 2.2 | 2.8 |
,| Placebo + Trastuzumab + Chemotherapy | 72.5 | -10.2 | -2.9 | -1.1 | 1.3 | 2.4 | 1.8 |
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
| Intervention | units on a scale (Mean) |
|---|
| Baseline: Body Image | Change at Week 13: Body Image | Change at Week 25: Body Image | Change at EOT: Body Image | Change at FU Month 18: Body Image | Change at FU Month 24: Body Image | Change at FU Month 36: Body Image | Baseline: Sexual Enjoyment | Change at Week 13: Sexual Enjoyment | Change at Week 25: Sexual Enjoyment | Change at EOT: Sexual Enjoyment | Change at FU Month 18: Sexual Enjoyment | Change at FU Month 24: Sexual Enjoyment | Change at FU Month 36: Sexual Enjoyment | Baseline: Sexual Function | Change at Week 13: Sexual Function | Change at Week 25: Sexual Function | Change at EOT: Sexual Function | Change at FU Month 18: Sexual Function | Change at FU Month 24: Sexual Function | Change at FU Month 36: Sexual Function | Baseline: FP | Change at Week 13: FP | Change at Week 25: FP | Change at EOT: FP | Change at FU Month 18: FP | Change at FU Month 24 : FP | Change at FU Month 36: FP |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 79.7 | -12.9 | -7.6 | -4.9 | -0.1 | 0.5 | 1.7 | 54.0 | -16.5 | -11.9 | -10.7 | -4.2 | -6.0 | -5.3 | 19.6 | -5.6 | -2.6 | -1.0 | 2.5 | 2.8 | 2.6 | 51.3 | 3.1 | 6.3 | 7.7 | 12.9 | 13.7 | 14.7 |
,| Placebo + Trastuzumab + Chemotherapy | 78.9 | -13.9 | -7.3 | -6.0 | -1.3 | 0.1 | 0.7 | 55.0 | -13.1 | -7.9 | -8.0 | -6.7 | -5.0 | -6.0 | 20.8 | -6.6 | -2.3 | -1.4 | 1.4 | 1.8 | 1.6 | 50.5 | 1.8 | 5.4 | 6.9 | 10.5 | 12.9 | 13.6 |
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
| Intervention | units on a scale (Mean) |
|---|
| Baseline: Physical | Change at Week 13: Physical | Change at Week 25: Physical | Change at EOT: Physical | Change at FU Month 18: Physical | Change at FU Month 24: Physical | Change at FU Month 36: Physical | Baseline: Role | Change at Week 13: Role | Change at Week 25: Role | Change at EOT: Role | Change at FU Month 18: Role | Change at FU Month 24: Role | Change at FU Month 36: Role | Baseline: Social | Change at Week 13: Social | Change at Week 25: Social | Change at EOT: Social | Change at FU Month 18: Social | Change at FU Month 24: Social | Change at FU Month 36: Social | Baseline: Cognitive | Change at Week 13: Cognitive | Change at Week 25: Cognitive | Change at EOT: Cognitive | Change at FU Month 18: Cognitive | Change at FU Month 24: Cognitive | Change at FU Month 36: Cognitive | Baseline: Emotional | Change at Week 13: Emotional | Change at Week 25: Emotional | Change at EOT: Emotional | Change at FU Month 18: Emotional | Change at FU Month 24: Emotional | Change at FU Month 36: Emotional |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 89.6 | -10.7 | -4.6 | -4.1 | -0.9 | -0.4 | -0.3 | 79.8 | -8.0 | -0.7 | 0.4 | 6.1 | 7.3 | 7.9 | 81.9 | -8.7 | -2.2 | 0.0 | 5.0 | 5.5 | 6.6 | 88.8 | -9.1 | -7.6 | -7.7 | -6.1 | -6.2 | -5.4 | 72.8 | 3.3 | 5.1 | 5.6 | 7.7 | 7.8 | 7.8 |
,| Placebo + Trastuzumab + Chemotherapy | 89.1 | -10.6 | -4.3 | -3.2 | -0.9 | -0.3 | -0.1 | 79.4 | -8.5 | 0.4 | 2.3 | 5.7 | 6.9 | 7.6 | 80.6 | -7.8 | -0.7 | 1.2 | 4.8 | 6.5 | 7.1 | 87.9 | -9.0 | -7.0 | -7.2 | -5.8 | -5.5 | -4.9 | 71.3 | 2.9 | 5.9 | 6.2 | 7.6 | 8.5 | 8.4 |
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
| Intervention | units on a scale (Mean) |
|---|
| Baseline | Change at Week 13 | Change at Week 25 | Change at EOT | Change at FU Month 18 | Change at FU Month 24 | Change at FU Month 36 |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 20.3 | 3.1 | 2.3 | -0.2 | -4.1 | -5.2 | -7.1 |
,| Placebo + Trastuzumab + Chemotherapy | 22.1 | 1.7 | -0.3 | -1.5 | -5.1 | -6.9 | -8.3 |
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
| Intervention | percentage of participants (Number) |
|---|
| Baseline: No problems | Baseline: Some problems | Baseline: Unable | Week 13: No problems | Week 13: Some problems | Week 13: Unable | Week 25: No problems | Week 25: Some problems | Week 25: Unable | EOT: No problems | EOT: Some problems | EOT: Unable | FU Month 18: No problems | FU Month 18: Some problems | FU Month 18: Unable | FU Month 24: No problems | FU Month 24: Some problems | FU Month 24: Unable | FU Month 36: No problems | FU Month 36: Some problems | FU Month 36: Unable |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 89.7 | 10.0 | 0.3 | 94.3 | 5.3 | 0.4 | 95.5 | 4.3 | 0.1 | 95.4 | 4.4 | 0.2 | 97.2 | 2.6 | 0.2 | 96.9 | 2.8 | 0.3 | 97.3 | 2.5 | 0.2 |
,| Placebo + Trastuzumab + Chemotherapy | 90.7 | 9.1 | 0.2 | 93.2 | 6.4 | 0.4 | 95.0 | 4.7 | 0.3 | 95.8 | 4.0 | 0.2 | 96.0 | 3.6 | 0.3 | 96.3 | 3.5 | 0.3 | 96.5 | 3.2 | 0.3 |
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
| Intervention | units on a scale (Mean) |
|---|
| Baseline:Systemic SE | Change at Week 13: Systemic SE | Change at Week 25: Systemic SE | Change at EOT: Systemic SE | Change at FU Month 18: Systemic SE | Change at FU Month 24: Systemic SE | Change at FU Month 36: Systemic SE | Baseline: Hair Loss | Change at Week 13: Hair Loss | Change at Week 25: Hair Loss | Change at EOT: Hair Loss | Change at FU Month 18: Hair Loss | Change at FU Month 24: Hair Loss | Change at FU Month 36: Hair Loss | Baseline: Arm Symptoms | Change at Week 13: Arm Symptoms | Change at Week 25: Arm Symptoms | Change at EOT: Arm Symptoms | Change at FU Month 18: Arm Symptoms | Change at FU Month 24: Arm Symptoms | Change at FU Month 36: Arm Symptoms | Baseline: Breast Symptoms | Change at Week 13: Breast Symptoms | Change at Week 25: Breast Symptoms | Change at EOT: Breast Symptoms | Change at FU Month 18: Breast Symptoms | Change at FU Month 24: Breast Symptoms | Change at FU Month 36: Breast Symptoms |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 9.5 | 21.1 | 9.2 | 8.3 | 4.4 | 4.1 | 4.5 | 26.4 | 17.3 | 8.3 | 10.9 | -7.0 | -4.1 | -5.6 | 21.6 | -4.7 | -2.9 | -3.5 | -4.0 | -5.1 | -5.9 | 19.5 | -5.0 | 1.9 | -0.6 | -3.0 | -6.4 | -7.3 |
,| Placebo + Trastuzumab + Chemotherapy | 10.2 | 21.7 | 8.2 | 7.5 | 5.5 | 4.9 | 5.2 | 22.1 | 21.2 | 14.5 | 17.9 | 3.2 | 0.7 | 2.4 | 21.7 | -2.1 | -2.3 | -3.4 | -3.9 | -5.0 | -4.7 | 20.4 | -5.2 | -0.4 | -3.8 | -5.9 | -7.3 | -7.9 |
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
| Intervention | Estimate of percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 97.65 |
| Placebo + Trastuzumab + Chemotherapy | 97.67 |
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
| Intervention | Estimate of percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 93.50 |
| Placebo + Trastuzumab + Chemotherapy | 92.51 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 2.7 |
| Placebo + Trastuzumab + Chemotherapy | 2.8 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 5.8 |
| Placebo + Trastuzumab + Chemotherapy | 7.2 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 7.9 |
| Placebo + Trastuzumab + Chemotherapy | 9.6 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 5.0 |
| Placebo + Trastuzumab + Chemotherapy | 6.0 |
Peak Serum Concentration (Cmax) of Pertuzumab
(NCT01358877)
Timeframe: Cycles 1, 10 and 15 (Cycle length=21 days)
| Intervention | mcg/mL (Mean) |
|---|
| Cycle 1 | Cycle 10 | Cycle 15 |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 237 | 222 | 206 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 8.0 |
| Placebo + Trastuzumab + Chemotherapy | 9.8 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 3.3 |
| Placebo + Trastuzumab + Chemotherapy | 3.7 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Chemotherapy | 7.1 |
| Placebo + Trastuzumab + Chemotherapy | 8.7 |
Change From Baseline in Heart Rate: Randomized Phase
Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
| Intervention | Beats per minute (Mean) |
|---|
| GSK1120212 2 mg in RP | 10.4 |
| Docetaxel 75 mg/m^2 in RP | 13.2 |
Change From Baseline in Heart Rate: Crossover Phase
Heart rate was measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation.The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
| Intervention | Beats per minute (Mean) |
|---|
| GSK1120212 2 mg in CP | 8.5 |
| Docetaxel 75 mg/m^2 in CP | 5.0 |
Number of Participants With Any SAE or Non-serious AE: Crossover Phase
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. (NCT01362296)
Timeframe: From the date of the first dose of study treatment in the Crossover Phase until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 12 months)
| Intervention | Participants (Number) |
|---|
| Any AE | Any SAE |
|---|
| Docetaxel 75 mg/m^2 in CP | 2 | 1 |
,| GSK1120212 2 mg in CP | 22 | 12 |
Number of Participants With a Best Response of Either a CR or PR as Assessed by the Investigator: Crossover Phase
Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or 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 [e.g., percent change from Baseline]). Participants with unknown or missing response were treated as non-responders. (NCT01362296)
Timeframe: From the date of the first dose of study treatment in the Crossover Phase until the first documented evidence of a CR or PR (maximum of 4 months)
| Intervention | Participants (Number) |
|---|
| CR | PR |
|---|
| Docetaxel 75 mg/m^2 in CP | 0 | 0 |
,| GSK1120212 2 mg in CP | 0 | 1 |
Number of Participants With a Best Response of Either a Complete Response (CR) or Partial Response (PR) as Assessed by the Investigator: Randomized Phase
Response was assessed by the investigator according to RECIST, version 1.1, using confirmed and unconfirmed responses. Responders were defined as participants achieving either a CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 millimeters [mm] in the short axis; without the appearance of new lesions) or 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 [e.g., percent change from Baseline]). Participants with unknown or missing response were treated as non-responders. (NCT01362296)
Timeframe: From randomization until the first documented evidence of a CR or PR (maximum of 10.2 months)
| Intervention | Participants (Number) |
|---|
| CR | PR |
|---|
| Docetaxel 75 mg/m^2 in RP | 0 | 5 |
,| GSK1120212 2 mg in RP | 0 | 10 |
GSK1120212 Plasma Pharmacokinetic (PK) Concentration
Blood samples for PK analysis of GSK1120212 were collected at the following time points: Cycle 1 (Study Day 15), Cycle 2 (Study Day 22), Cycle 3 (Study Day 43), and Cycle 4 (Study Day 64). Post-dose PK samples collected on Day 15 of Cycle 1 occurred at least 1 hour apart. Participants were instructed to withhold the dose of GSK1120212 until after blood for PK samples had been drawn. Pre-dose samples were taken 15 minutes or less prior to taking the next dose (i.e., trough). (NCT01362296)
Timeframe: Day 15 of Cycle 1: pre-dose; 0.5-2 hours, 2-4 hours, and 4-8 hours post-dose; Day 1 of Cycle 2, Cycle 3 and Cycle 4: pre-dose
| Intervention | Nanograms (ng)/milliliter (mL) (Mean) |
|---|
| Cycle 1, Day 15, pre-dose, n=80 | Cycle 1, Day 15, 0.5-2 hours post-dose, n=78 | Cycle 1, Day 15, 2-4 hours post-dose, n=77 | Cycle 1, Day 15, 4-8 hours post-dose, n=78 | Cycle 2, Day 1, pre-dose, n=75 | Cycle 3, Day 1, pre-dose, n=60 | Cycle 4, Day 1, pre-dose, n=38 |
|---|
| GSK1120212 2 mg in RP | 16.1 | 21.5 | 29.7 | 24.8 | 16.7 | 12.9 | 13.9 |
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP): Randomized Phase
Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle thereafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
| Intervention | millimeters of mercury (mmHg) (Mean) |
|---|
| SBP, Worst-case on-therapy | DBP, Worst-case on-therapy |
|---|
| Docetaxel 75 mg/m^2 in RP | 3.1 | 2.5 |
,| GSK1120212 2 mg in RP | 13.5 | 10.7 |
Change From Baseline in SBP and DBP: Crossover Phase
Systolic and diastolic blood pressure were measured at the following scheduled time points: Baseline; Days 1, 8, and 15 of Cycle 1 (Study Week 1); and Day 1 of every cycle therafter until treatment discontinuation. The worst-case on-therapy was determined using both scheduled and unscheduled assessments during the on-therapy period. Change from Baseline was calculated as the value at post-Baseline time point minus the value at Baseline. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
| Intervention | mmHg (Mean) |
|---|
| SBP, Worst-case on-therapy | DBP, Worst-case on-therapy |
|---|
| Docetaxel 75 mg/m^2 in CP | -15.0 | -12.0 |
,| GSK1120212 2 mg in CP | 8.7 | 8.3 |
Progression-Free Survival (PFS) as Assessed by the Investigator (INV)
PFS is defined as the time from RAN until the earliest date of documented radiological PD or DT due to any cause. PD was assessed by the INV according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. For participants (PAR) who did not have a documented date of PD or DT, PFS was censored at the date of the last adequate assessment. For PAR who received subsequent anti-cancer therapy prior to the date of documented PD or DT, PFS was censored at the date of the last adequate assessment prior to the initiation of therapy. (NCT01362296)
Timeframe: From randomization (RAN) until the earliest date of documented radiological disease progression (PD) or death (DT) due to any cause (maximum of 10.2 months)
| Intervention | Weeks (Median) |
|---|
| GSK1120212 2 mg in RP | 11.7 |
| Docetaxel 75 mg/m^2 in RP | 11.4 |
Overall Survival (OS)
OS is defined as the interval of time between the date of randomization and the date of death due to any cause. For participants who did not die, OS was censored at the date of last contact. (NCT01362296)
Timeframe: Time interval between the date of randomization and the date of death due to any cause (maximum of 22 months)
| Intervention | Months (Median) |
|---|
| GSK1120212 2 mg in RP | 8.1 |
| Docetaxel 75 mg/m^2 in RP | 9.9 |
Duration of Response (DOR) as Assessed by the Investigator: Randomized Phase
DOR was assessed by the investigator for participants with CR (disappearance of all target and non-target lesions; any pathological lymph nodes must be <10 mm in the short axis; without the appearance of new lesions) or 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 [e.g., percent change from Baseline]). DOR is defined as the time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause. PD is defined as at least a 20% increase in the sum of the diameters (SD) of target lesions with an absolute increase of at least 5 millimeters (mm) or the appearance of at least 1 new lesion, or the worsening of non-target lesions significant enough to require study treatment discontinuation. (NCT01362296)
Timeframe: Time from the first documented evidence of CR or PR until the earliest date of documented radiological progression or death due to any cause (maximum of 10.2 months)
| Intervention | Weeks (Mean) |
|---|
| GSK1120212 2 mg in RP | 6.7 |
| Docetaxel 75 mg/m^2 in RP | 12.4 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Randomized Phase
Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, myelocytes, neutrophil bands (%). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.). (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
| Intervention | Participants (Number) |
|---|
| Atypical lymphs, Decrease to low, n=0, 3 | Atypical lymphs, CTN or no change, n=0, 3 | Atypical lymphs, Increase to high, n=0, 3 | Atypical lymphs (%), Decrease to low, n =0, 3 | Atypical lymphs (%), CTN or no change, n=0, 3 | Atypical lymphs (%), Increase to high, n=0, 3 | Basophils, Decrease to low, n=86, 43 | Basophils, CTN or no change, n=86, 43 | Basophils, Increase to high, n=86,43 | Eosinophils, Decrease to low, n=86, 43 | Eosinophils, CTN or no change, n=86, 43 | Eosinophils, Increase to high, n=86, 43 | Metamyelocytes, Decrease to low, n=1, 7 | Metamyelocytes, CTN or no change, n=1, 7 | Metamyelocytes, Increase to high, n=1, 7 | Monocytes, Decrease to low, n=86, 43 | Monocytes, CTN or no change, n=86, 43 | Monocytes, Increase to high, n=86, 43 | Myelocytes, Decrease to low, n=1, 9 | Myelocytes, CTN or no change, n=1, 9 | Myelocytes, Increase to high, n=1, 9 | Neutrophil Bands (%), Decrease to low, n=1, 4 | Neutrophil Bands (%), CTN or no change, n=1, 4 | Neutrophil Bands (%), Increase to high, n=1, 4 |
|---|
| Docetaxel 75 mg/m^2 in RP | 0 | 0 | 3 | 0 | 0 | 3 | 0 | 41 | 2 | 1 | 42 | 0 | 0 | 0 | 7 | 20 | 18 | 9 | 0 | 1 | 8 | 0 | 3 | 1 |
,| GSK1120212 2 mg in RP | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 82 | 4 | 1 | 77 | 9 | 0 | 0 | 1 | 3 | 78 | 5 | 0 | 0 | 1 | 0 | 1 | 0 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Hematology Parameters: Crossover Phase
Data are presented for only those hematology parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Hematology parameters included: atypical lymphs, atypical lymphs (percentage [%]), basophils, eosinophils, metamyelocytes, monocytes, and myelocytes. Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.). (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
| Intervention | Participants (Number) |
|---|
| Atypical lymphs, Decrease to low, n=3, 1 | Atypical lymphs, CTN or no change, n=3, 1 | Atypical lymphs, Increase to high, n=3, 1 | Atypical lymphs (%), Decrease to low, n=3, 1 | Atypical lymphs (%), CTN or no change, n=3, 1 | Atypical lymphs (%), Increase to high, n=3, 1 | Basophils, Decrease to low, n=23, 1 | Basophils, CTN or no change, n=23, 1 | Basophils, Increase to high, n=23, 1 | Eosinophils, Decrease to low, n=23, 1 | Eosinophils, CTN or no change, n=23, 1 | Eosinophils, Increase to high, n=23, 1 | Metamyelocytes, Decrease to low, n=1, 1 | Metamyelocytes, CTN or no change, n=1, 1 | Metamyelocytes, Increase to high, n=1, 1 | Monocytes, Decrease to low, n=23, 1 | Monocytes, CTN or no change, n=23, 1 | Monocytes, Increase to high, n=23, 1 | Myelocytes, Decrease to low, n=3, 1 | Myelocytes, CTN or no change, n=3, 1 | Myelocytes, Increase to high, n=3, 1 |
|---|
| Docetaxel 75 mg/m^2 in CP | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 |
,| GSK1120212 2 mg in CP | 0 | 1 | 2 | 0 | 1 | 2 | 0 | 23 | 0 | 0 | 23 | 0 | 0 | 0 | 1 | 1 | 20 | 2 | 0 | 0 | 3 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Randomized Phase
Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.). (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
| Intervention | Participants (Number) |
|---|
| Lactate dehydrogenase, Decrease to low, n=87, 43 | Lactate dehydrogenase, CTN or no change, n=87, 43 | Lactate dehydrogenase, Increase to high, n=87, 43 | Total Protein, Decrease to low, n=86, 43 | Total Protein, CTN or no change, n=86, 43 | Total Protein, Increase to high, n=86, 43 | Urea/BUN, Decrease to low, n=87, 43 | Urea/BUN, CTN or no change, n=87, 43 | Urea/BUN, Increase to high, n=87,43 |
|---|
| Docetaxel 75 mg/m^2 in RP | 0 | 23 | 20 | 12 | 31 | 0 | 0 | 34 | 9 |
,| GSK1120212 2 mg in RP | 1 | 40 | 46 | 31 | 55 | 1 | 0 | 62 | 25 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline With Respect to Normal Ranges in the Indicated Clinical Chemistry Parameters: Crossover Phase
Data are presented for only those clinical chemistry parameters for which the following worst-case on-therapy changes from Baseline with respect to the normal range were observed: decrease to low, change to normal (CTN) or no change, or increase to high. Clinical chemistry parameters included: lactate dehydrogenase, total protein, and urea/blood urea nitrogen (BUN). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. Normal ranges for each parameter may vary depending on the laboratory (central versus local) and the participant (age, gender, etc.). (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
| Intervention | Participants (Number) |
|---|
| Lactate dehydrogenase, Decrease to low | Lactate dehydrogenase, CTN or no change | Lactate dehydrogenase, Increase to high | Total Protein, Decrease to low | Total Protein, CTN or no change | Total Protein, Increase to high | Urea/BUN, Decrease to low | Urea/BUN, CTN or no change | Urea/BUN, Increase to high |
|---|
| Docetaxel 75 mg/m^2 in CP | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 |
,| GSK1120212 2 mg in CP | 0 | 15 | 8 | 15 | 8 | 0 | 0 | 18 | 5 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Randomized Phase
Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
| Intervention | Participants (Number) |
|---|
| Haemoglobin (inc), IAG, n=87, 43 | Haemoglobin (inc), Increase to G3, n=87, 43 | Haemoglobin (inc), Increase to G4, n=87, 43 | Haemoglobin (anemia), IAG, n=86, 43 | Haemoglobin (anemia), Increase to G3, n=86, 43 | Haemoglobin (anemia), Increase to G4, n=86, 43 | Lymphocyte ct (inc), IAG, n=86, 43 | Lymphocyte ct (inc), Increase to G3, n=86, 43 | Lymphocyte ct (inc), Increase to G4, n=86, 43 | Lymphocyte ct (dec), IAG, n=85, 43 | Lymphocyte ct (dec), Increase to G3, n=85, 43 | Lymphocyte ct (dec), Increase to G4, n=85, 43 | ANC, IAG, n=86, 43 | ANC, Increase to G3, n=86, 43 | ANC, Increase to G4, n=86, 43 | Platelet ct, IAG, n=87, 43 | Platelet ct, Increase to G3, n=87, 43 | Platelet ct, Increase to G4, n=87, 43 | WBC, IAG, n=87, 43 | WBC, Increase to G3, n=87, 43 | WBC, Increase to G4, n=87, 43 |
|---|
| Docetaxel 75 mg/m^2 in RP | 0 | 0 | 0 | 27 | 3 | 0 | 2 | 0 | 0 | 19 | 2 | 0 | 34 | 13 | 13 | 3 | 0 | 0 | 33 | 17 | 0 |
,| GSK1120212 2 mg in RP | 0 | 0 | 0 | 34 | 8 | 0 | 9 | 1 | 0 | 18 | 4 | 0 | 5 | 0 | 0 | 15 | 0 | 0 | 5 | 0 | 1 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Hematology Parameters: Crossover Phase
Hematology parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G (IAG), G3, or G4 occurred. Hematology parameters included: haemoglobin (increased [inc]), haemoglobin (anemia), lymphocyte count (ct) (inc), lymphocyte ct (decreased [dec]), total absolute neutrophil count (ANC), platelet ct, and white blood cell count (WBC). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
| Intervention | Participants (Number) |
|---|
| Haemoglobin (inc), IAG, n=23, 1 | Haemoglobin (inc), Increase to G3, n=23, 1 | Haemoglobin (inc), Increase to G4, n=23, 1 | Haemoglobin (anemia), IAG, n=23, 1 | Haemoglobin (anemia), Increase to G3, n=23, 1 | Haemoglobin (anemia), Increase to G4, n=23, 1 | Lymphocyte ct (inc), IAG, n=23, 1 | Lymphocyte ct (inc), Increase to G3, n=23, 1 | Lymphocyte ct (inc), Increase to G4, n=23, 1 | Lymphocyte ct (dec), IAG, n=23, 1 | Lymphocyte ct (dec), Increase to G3, n=23, 1 | Lymphocyte ct (dec), Increase to G4, n=23, 1 | ANC, IAG, n=19, 0 | ANC, Increase to G3, n=19, 0 | ANC, Increase to G4, n=19, 0 | Platelet ct, IAG, n=23, 1 | Platelet ct, Increase to G3, n=23, 1 | Platelet ct, Increase to G4, n=23, 1 | WBC, IAG, n=23, 1 | WBC, Increase to G3, n=23, 1 | WBC, Increase to G4, n=23, 1 |
|---|
| Docetaxel 75 mg/m^2 in CP | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| GSK1120212 2 mg in CP | 0 | 0 | 0 | 12 | 2 | 0 | 1 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Randomized Phase
Clinical chemistry parameters were summarized according to National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any G, G3, or G4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Randomized Phase (up to Study Week 40)
| Intervention | Participants (Number) |
|---|
| Albumin, Increase to any G (IAG), n=86, 43 | Albumin, Increase to G3, n=86, 43 | Albumin, Increase to G4, n=86, 43 | ALKP, IAG, n=85, 43 | ALKP, Increase to G3, n =85, 43 | ALKP, Increase to G4, n=85, 43 | ALT, IAG, n=87, 43 | ALT, Increase to G3, n=87, 43 | ALT, Increase to G4, n=87, 43 | AST, IAG, n=86, 43 | AST, Increase to G3, n=86, 43 | AST, Increase to G4, n=86, 43 | Total bilirubin, IAG, n=85, 42 | Total bilirubin, Increase to G3, n=85, 42 | Total bilirubin, Increase to G4, n=85, 42 | Calcium (hypercalcemia), IAG, n =87, 43 | Calcium (hypercalcemia), Increase to G3, n=87, 43 | Calcium (hypercalcemia), Increase to G4, n=87, 43 | Calcium (hypocalcemia), IAG, n=87, 43 | Calcium (hypocalcemia), Increase to G3, n=87, 43 | Calcium (hypocalcemia), Increase to G4, n=87, 43 | Creatine kinase, IAG, n=1, 0 | Creatine kinase, Increase to G3, n=1, 0 | Creatine kinase, Increase to G4, n=1, 0 | Creatinine, IAG, n=87, 43 | Creatinine, Increase to G3, n=87, 43 | Creatinine, Increase to G4, n=87, 43 | Glucose (hyperglycemia), IAG, n=87, 43 | Glucose (hyperglycemia), Increase to G3, n=87, 43 | Glucose (hyperglycemia), Increase to G4, n=87, 43 | Glucose (hypoglycemia), IAG, n=87, 43 | Glucose (hypoglycemia), Increase to G3, n=87, 43 | Glucose (hypoglycemia), Increase to G4, n=87, 43 | Potassium (hyperkalemia), IAG, n=86, | Potassium (hyperkalemia), Increase to G3, n=86, 43 | Potassium (hyperkalemia), Increase to G4, n=86, 43 | Potassium (hypokalemia), IAG, n=86, 43 | Potassium (hypokalemia), Increase to G3, n=86, 43 | Potassium (hypokalemia), Increase to G4, n=86, 43 | Sodium (hypernatremia), IAG, n=87, 43 | Sodium (hypernatremia), Increase to G3, n=87, 43 | Sodium (hypernatremia), Increase to G4, n=87, 43 | Sodium (hyponatremia), IAG, n=87, 43 | Sodium (hyponatremia), Increase to G3, n=87, 43 | Sodium (hyponatremia), Increase to G4, n=87, 43 |
|---|
| Docetaxel 75 mg/m^2 in RP | 21 | 1 | 0 | 3 | 1 | 0 | 7 | 1 | 0 | 11 | 0 | 0 | 3 | 0 | 0 | 3 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 6 | 1 | 0 | 24 | 2 | 0 | 4 | 0 | 0 | 4 | 1 | 0 | 2 | 0 | 0 | 2 | 0 | 0 | 5 | 1 | 0 |
,| GSK1120212 2 mg in RP | 57 | 4 | 0 | 26 | 2 | 0 | 32 | 3 | 0 | 55 | 1 | 0 | 3 | 0 | 0 | 9 | 0 | 0 | 4 | 0 | 1 | 0 | 0 | 0 | 12 | 3 | 0 | 47 | 5 | 0 | 4 | 0 | 0 | 9 | 1 | 0 | 8 | 0 | 0 | 12 | 0 | 0 | 16 | 2 | 0 |
Number of Participants With the Indicated Worst-case On-therapy Change From Baseline in the Indicated Clinical Chemistry Parameters: Crossover Phase
Clinical chemistry parameters were summarized according to NCI CTCAE grade, version 4.0. Grade (G) 1, Mild; Grade 2, Moderate; Grade 3 (G3), Severe; Grade 4 (G4), Life-threatening or disabling; Grade 5, Death. Data are presented for only those parameters for which an increase to any grade, Grade 3, or Grade 4 occurred. Clinical chemistry parameters included: albumin, alkaline phosphatase (ALKP), alanine amino transferase (ALT), aspartate amino transferase (AST), total bilirubin, calcium (hypercalcemia), calcium (hypocalcemia), creatine kinase, creatinine, glucose (hyperglycemia), glucose (hypoglycemia), potassium (hyperkalemia), potassium (hypokalemia), sodium (hypernatremia), and sodium (hyponatremia). Worst-case on-therapy changes from Baseline were summarized. Worst-case on-therapy was defined using the on-therapy window and changes were indentified using both scheduled and unscheduled assessments. (NCT01362296)
Timeframe: Baseline; Days 1, 8, and 15 of Cycle 1; and Day 1 of every cycle thereafter until treatment discontinuation of the Crossover Phase (up to Study Week 19)
| Intervention | Participants (Number) |
|---|
| Albumin, Increase to any G (IAG), n=23, 1 | Albumin, Increase to G3, n=23, 1 | Albumin, Increase to G4, n=23, 1 | ALKP, IAG, n=23, 1 | ALKP, Increase to G3, n =23, 1 | ALKP, Increase to G4, n=23, 1 | ALT, IAG, n=23, 1 | ALT, Increase to G3, n=23, 1 | ALT, Increase to G4, n=23, 1 | AST, IAG, n=23, 1 | AST, Increase to G3, n=23, 1 | AST, Increase to G4, n=23, 1 | Total bilirubin, IAG, n=22, 1 | Total bilirubin, Increase to G3, n=22, 1 | Total bilirubin, Increase to G4, n=22, 1 | Calcium (hypercalcemia), IAG, n =23, 1 | Calcium (hypercalcemia), Increase to G3, n=23, 1 | Calcium (hypercalcemia), Increase to G4, n=23, 1 | Calcium (hypocalcemia), IAG, n=23, 1 | Calcium (hypocalcemia), Increase to G3, n=23, 1 | Calcium (hypocalcemia), Increase to G4, n=23, 1 | Creatine kinase, IAG, n=1, 0 | Creatine kinase, Increase to G3, n=1, 0 | Creatine kinase, Increase to G4, n=1, 0 | Creatinine, IAG, n=23, 1 | Creatinine, Increase to G3, n=23, 1 | Creatinine, Increase to G4, n=23, 1 | Glucose (hyperglycemia), IAG, n=23, 1 | Glucose (hyperglycemia), Increase to G3, n=23, 1 | Glucose (hyperglycemia), Increase to G4, n=23, 1 | Glucose (hypoglycemia), IAG, n=23, 1 | Glucose (hypoglycemia), Increase to G3, n=23, 1 | Glucose (hypoglycemia), Increase to G4, n=23, 1 | Potassium (hyperkalemia), IAG, n=23, 1 | Potassium (hyperkalemia), Increase to G3, n=23, 1 | Potassium (hyperkalemia), Increase to G4, n=23, 1 | Potassium (hypokalemia), IAG, n=23, 1 | Potassium (hypokalemia), Increase to G3, n=23, 1 | Potassium (hypokalemia), Increase to G4, n=23, 1 | Sodium (hypernatremia), IAG, n=23, 1 | Sodium (hypernatremia), Increase to G3, n=23, 1 | Sodium (hypernatremia), Increase to G4, n=23, 1 | Sodium (hyponatremia), IAG, n=23, 1 | Sodium (hyponatremia), Increase to G3, n=23, 1 | Sodium (hyponatremia), Increase to G4, n=23, 1 |
|---|
| Docetaxel 75 mg/m^2 in CP | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| GSK1120212 2 mg in CP | 15 | 4 | 0 | 10 | 1 | 0 | 7 | 1 | 0 | 9 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 3 | 0 | 0 | 10 | 0 | 0 | 1 | 0 | 0 | 3 | 1 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 3 | 2 | 0 |
Number of Participants With Any Serious Adverse Event (SAE) or Non-serious Adverse Event (AE): Randomized Phase
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury. Medical or scientific judgment should have been exercised in deciding whether reporting was appropriate in other situations. Refer to the general Adverse AE/SAE module for a complete list of AEs and SAEs. (NCT01362296)
Timeframe: From randomization until 30 days following discontinuation of study treatment regardless of initiation of a new cancer therapy or transfer to hospice (maximum of 19 months)
| Intervention | Participants (Number) |
|---|
| Any AE | Any SAE |
|---|
| Docetaxel 75 mg/m^2 in RP | 43 | 9 |
,| GSK1120212 2 mg in RP | 87 | 32 |
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.
| Intervention | Participants (Count of Participants) |
|---|
| Adverse Events | Treatment-Related Adverse Events | Serious Adverse Events | Treatment-Related Serious Adverse Events |
|---|
| Cohort A (GSK1120212 < 24 Weeks) | 119 | 101 | 26 | 8 |
,| Cohort B (GSK1120212 >= 24 Weeks) | 30 | 26 | 13 | 4 |
Overall Survival (OS) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.
OS is calculated from the date of randomization until death from any cause. (NCT01395758)
Timeframe: Date of randomization to the date of death from any cause, assessed up to 24 months
| Intervention | months (Median) |
|---|
| Tivantinib Plus Erlotinib Arm | 6.8 |
| Chemotherapy Arm | 8.5 |
Progression-free Survival (PFS) Among Subjects With KRAS Mutation Positive NSCLC (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Single Agent Chemotherapy.
Progression is defined using Response Evaluation Criteria in Solid Tumors (RECIST v 1.1) criteria 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. The appearance of one or more new lesions or progression of existing non-target lesions are also considered progression. (NCT01395758)
Timeframe: Date of randomization until disease progression per RECIST (v 1.1) or death from any cause, whichever came first, assessed up to 24 months.
| Intervention | weeks (Median) |
|---|
| Tivantinib Plus Erlotinib Arm | 7.3 |
| Chemotherapy Arm | 18.6 |
ORR Among Subjects in the Crossover Period Treated With Erlotinib Plus Tivantinib
Per RECIST v1.1, CR = disappearance of all lesions and PR = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects. (NCT01395758)
Timeframe: Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months.
| Intervention | Participants (Count of Participants) |
|---|
| Tivantinib Plus Erlotinib Crossover Period | 2 |
Objective Response Rate (ORR) Among All Eligible Subjects (ITT Population) Treated With Erlotinib Plus Tivantinib Compared to Chemotherapy.
Per RECIST v1.1, Complete Response (CR) = disappearance of all lesions and Partial Response (PR) = at least 30% decrease in the sum of diameters of target lesions. ORR = (CR+PR)/# subjects. (NCT01395758)
Timeframe: Date of randomization to the date of death from any cause or to the date that the subject discontinues from the study, assessed up to 24 months
| Intervention | Participants (Count of Participants) |
|---|
| Tivantinib Plus Erlotinib Arm | 0 |
| Chemotherapy Arm | 4 |
Overall Objective Response
"Overall objective response measured using Response Evaluation Criteria in Solid Tumors (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 the diameters of target lesions, taking as reference the baseline sum diameters.~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. (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 sum diameters while on study." (NCT01418001)
Timeframe: Every 6 weeks up to 2 years
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Stable Disease (SD) |
|---|
| Level 1: Pazopanib 400 mg QD | 3 | 2 |
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
| Intervention | months (Median) |
|---|
| Cisplatin + Docetaxel + Cetuximab | 4.8 |
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
| Intervention | participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | Overall Response (OR) | Stable disease (SD) | Progressive disease (PD) |
|---|
| Cisplatin + Docetaxel + Cetuximab | 1 | 14 | 15 | 5 | 6 |
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
| Intervention | months (Median) |
|---|
| Cisplatin + Docetaxel + Cetuximab | 14.7 |
Pathologic Response Rate
The percentage of patients with a major pathologic response (NCT01443078)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| All Patients | 17 |
Time of Overall Survival (OS)
To assess the time of overall survival of patients receiving Chloroquine + Taxane or Taxane-like chemotherapy (NCT01446016)
Timeframe: a median of 25.4 months, up to 83.5 months
| Intervention | months (Median) |
|---|
| Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy | 25.4 |
Overall Response Rate (ORR)
"To determine the anti-tumor activity of the combination of Chloroquine + Taxane or Taxane-like chemo agents (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) (C/T) measured by overall Response Rate (ORR) defined as percentage of patients having complete or partial response in 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., or similar definition that is accurate and appropriate.~The study was designed to compare the ORR with the published percentage of 30% (docetaxel 100 mg/ml2 every 3 weeks for maximum of 10 cycles)." (NCT01446016)
Timeframe: 3-week cycles for maximum of 6 cycles (4.5 months)
| Intervention | percentage of participants (Number) |
|---|
| Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy | 45.16 |
Time to Progression Free Survival (PFS)
"To assess the time to progression free survival of patients treated with the combination of Chloroquine and Taxane or Taxane-Like chemotherapy. Progression is defined as time from initiation of chemotherapy to disease progression 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 similar definition as accurate and appropriate." (NCT01446016)
Timeframe: 25.4 months (median)
| Intervention | months (Median) |
|---|
| Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy | 12.4 |
Number of Patients Who Experienced Grade 3 of Greater Adverse Events
To assess how many patients experienced grade 3 or greater adverse events when receiving the combination of Chloroquine and Taxane or Taxane-Like chemotherapy. Toxicity was assessed for all enrolled patients who received one or more doses of the study drug combination by Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. (NCT01446016)
Timeframe: 25.4 months (median)
| Intervention | Participants (Count of Participants) |
|---|
| Chloroquine With Taxane or Taxane-Like (Paclitaxel, Docetaxel, Abraxane, Ixabepilone) Chemotherapy | 4 |
Objective Response Rate (ORR)
The ORR was defined as the proportion of participants with best overall response of complete response (CR) or partial response (PR) per RECIST criteria. The ORR was estimated by study arm based on the tumor response evaluation as determined by the investigator, according to RECIST 1.1. Participants with unknown response were treated as non-responders. The statistical difference in ORR between treatment arms was evaluated using the Cochran-Mantel-Haenszel (CMH) chi-square test with histology, TPC option, and geographic region as strata, tested at an alpha level of 0.05 (2-sided). The 95 percent confidence interval (CI) was calculated using Clopper Pearson method. (NCT01454934)
Timeframe: Randomization (Day 1) to CR or PR
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Eribulin Mesylate | 12.2 |
| Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed | 15.2 |
Overall Survival (OS)
The OS was defined as the time in months from the date of randomization to the date of death, regardless of cause. In the absence of confirmation of death, the participants were censored either at the date that participant was last known to be alive or the date of study cut-off, whichever was earlier. The two treatment arms were compared using the log-rank test, stratified by histology, TPC option, and geographic region; and the treatment difference between eribulin mesylate and TPC was tested at a significance level of 0.05 (2-sided). Kaplan-Meier (K-M) survival probabilities for each arm were plotted over time. The treatment effect was estimated by fitting a Cox Proportional Hazards model to the OS times including treatment arm as a factor and histology, TPC option and geographic region as strata. (NCT01454934)
Timeframe: Randomization (Day 1) until date of death from any cause, or 37 months
| Intervention | months (Median) |
|---|
| Arm A: Eribulin Mesylate | 9.5 |
| Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed | 9.5 |
Progression Free Survival (PFS) by Response Evaluation Criteria in Solid Tumors (RECIST)
PFS was defined as the time from the date of randomization to the date of first documentation of disease progression, or date of death, whichever occurred first. The difference in PFS (based on the tumor response evaluation as determined by the investigator) between eribulin mesylate and TPC was evaluated using the log rank test, stratified by histology, TPC option, and geographic region, tested at an alpha level of 0.05 (2-sided). PFS censoring rules will be defined in the SAP and follow Federal Department of Agriculture (FDA) guidance. (NCT01454934)
Timeframe: Randomization (Day 1) until date of disease progression or death (whichever occurred first), or 37 months
| Intervention | months (Median) |
|---|
| Arm A: Eribulin Mesylate | 3.0 |
| Arm B: Vinorelbine, Gemcitabine, Docetaxel, or Pemetrexed | 2.8 |
Overall Survival (OS)
OS (in months) will be measured from date of first dose until death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. (NCT01459614)
Timeframe: Up to 28 months
| Intervention | Months (Median) |
|---|
| Primary Cohort (21 Day Cycle) | 13.42 |
Percentage of Participants Without Disease Progression (Progression-Free Survival) at 6 Months
PFS is defined as the percentage of patients with disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause at 6 months. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. (NCT01459614)
Timeframe: 6 months
| Intervention | percentage of participants (Number) |
|---|
| Primary Cohort (21 Day Cycle) | 78.6 |
| Expansion Cohort (28 Day Cycle) | 30 |
Progression-free Survival (PFS)
PFS is defined as the the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause . Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. (NCT01459614)
Timeframe: Up to 21 months
| Intervention | Months (Median) |
|---|
| Primary Cohort (21 Day Cycle) | 8.4 |
| Expansion Cohort (28 Day Cycle) | 4.1 |
Disease Control Rate (DCR)
DCR is defined as the percentage of patients achieving a complete response (CR), partial response (PR), or stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. (NCT01459614)
Timeframe: Up to 22 months
| Intervention | Percentage of Participants (Number) |
|---|
| Primary Cohort (21 Day Cycle) | 89 |
Maximum Tolerated Dose (MTD) of Pasireotide in Combination With Docetaxel and Prednisone by the Occurrence of Adverse Events and the Associated Grade Per NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
To identify the maximum tolerated dose (MTD) of pasireotide, The occurrence rate of binary endpoints (eg, specific types of toxicity at a certain dose level and severity grade, response, etc) will be described by point estimates and exact 90% confidence intervals (CIs) for proportions using Wilson's method. (NCT01468532)
Timeframe: Up to day 57
| Intervention | mg (Number) |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | 60 |
Time to Progression (TTP)
Time from Treatment start date to Progression (TTP) 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 (NCT01468532)
Timeframe: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study, up to 2 years
| Intervention | months (Median) |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | 7.2 |
Measurement of Levels of IGF-1, Serum Chromogranin A (SCA), and Neuron Specific Enolase (NSE), the Change Between Time Points Pre-therapy, Post-therapy
Measurement of levels of IGF-1, serum chromogranin A (SCA), and neuron specific enolase (NSE), the change between time points (day 22 and day 43) from day 1 as measured in percent change. (NCT01468532)
Timeframe: Baseline and days 22 and 43
| Intervention | percent change of biomarker from day 1 (Median) |
|---|
| IGF-1 day 1 to day 22 | IGF-1 day 1 to day 43 | SCA day 1 to day 22 | SCA day 1 to day 43 | NSE day 1 to day 22 | NSE day 1 to day 43 |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | -47.74 | -65.64 | -25.36 | -21.43 | -17.00 | 8.00 |
Measurements of CTC Counts, the Change Between Time-points Pre-therapy, Post-therapy
Measurements of CTC counts, the change between time-points (day 22 and day 43) from day 1 as measured in percent change. (NCT01468532)
Timeframe: Baseline and days 22 and 43
| Intervention | percent change of CTC from day 1 (Median) |
|---|
| CTC from day 1 to day 22 | CTC from day 1 to day 43 |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | -5.50 | -29.50 |
Percentage Prostate-specific Antigen (PSA) Change Noted
Percentage change of prostate-specific antigen (PSA) decline or increase noted (NCT01468532)
Timeframe: On days 1, 22, 43
| Intervention | percentage change of PSA from day 1 (Median) |
|---|
| from day 1 to day 22 | from day 1 to day 43 |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | -18.52 | -31.49 |
Pharmacokinetics (PK) of SOM230
Pharmacokinetics (PK) of SOM230 measured in the bloodstream (in ng/ml) at days 29, 57, and 85. (NCT01468532)
Timeframe: Predosing/end of infusion/2, 3, 4 ,7, 24 and 48 hours after start of docetaxel; Day 43; predosing for docetaxel and pasireotide/end of infusion/2, 3, 4, 7, 24 hours day 44/48 hours day 45 after start of infusion; days 29, 57, and 85 prior to pasireotide
| Intervention | ng/ml (Median) |
|---|
| Level at day 29 | Level at day 57 | Level at day 85 |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | 15.4 | 14.9 | 14.5 |
The Number of Patients With Toxicity as Assessed Via NCI CTCAE Version 4.0
The count of patients who experience a given type and grade of toxicity as assessed via NCI CTCAE version 4.0 (NCT01468532)
Timeframe: On days 1, 8, 15, 22, 29, 36 43, 50 and 57
| Intervention | Participants (Count of Participants) |
|---|
| Abdominal pain grade 1 | Agitation grade 1 | Alkaline phosphatase increased grade 3 | Allergic reaction grade 1 | Alopecia grade 1 | Alopecia grade 2 | Anemia grade 1 | Anemia grade 3 | Anorexia grade 1 | Anorexia grade 2 | Arthritis grade 1 | Aspartate aminotransferase increased grade 2 | Aspartate aminotransferase increased grade 3 | Back pain grade 1 | Back pain grade 2 | Bladder infection grade 2 | Blood and lymphatic system disorders-Other grade 1 | Bruising grade 1 | Cardiac disorders - Other, specify grade 1 | Cataract grade 1 | Chills grade 1 | Cholesterol high grade 1 | Conjunctivitis grade 2 | Constipation grade 1 | Cough grade 1 | Cough grade 2 | Creatinine increased grade 1 | Dehydration grade 2 | Dehydration grade 3 | Depression grade 1 | Diarrhea grade 1 | Diarrhea grade 2 | Diarrhea grade 3 | Dizziness grade 1 | Dry mouth grade 1 | Dry skin grade 1 | Dysgeusia grade 1 | Dysgeusia grade 2 | Dyspnea grade 1 | Ear and labyrinth disorders-Other, specify grade 1 | Edema limbs grade 1 | Edema limbs grade 2 | EKG QT corrected interval prolong grade 1 | EKG QT corrected interval prolong grade 2 | EKG QT corrected interval prolong grade 3 | Eye disorders - Other, specify grade 1 | Fatigue grade 1 | Fatigue grade 2 | Fatigue grade 3 | Fever grade 1 | Flank pain grade 1 | Flu like symptoms grade 1 | Flushing grade 1 | Gastroesophageal reflux disease grade 1 | Gastroesophageal reflux disease grade 2 | Gastrointestinal disorders -Other, specify grade 1 | Generalized muscle weakness grade 1 | Generalized muscle weakness grade 2 | Headache grade 1 | Hearing impaired grade 1 | Heart failure grade 1 | Hematuria grade 1 | Hematuria grade 2 | Hoarseness grade 1 | Hot flashes grade 1 | Hyperglycemia grade 1 | Hyperglycemia grade 2 | Hyperglycemia grade 3 | Hyperkalemia grade 2 | Hypertension grade 2 | Hypertension grade 3 | Hypertriglyceridemia grade 1 | Hypertriglyceridemia grade 3 | Hypoalbuminemia grade 3 | Hypocalcemia grade 1 | Hypocalcemia grade 3 | Hypokalemia grade 2 | Hypomagnesemia grade 1 | Hypomagnesemia grade 2 | Hyponatremia grade 3 | Hypophosphatemia grade 3 | Hypotension grade 3 | Hypothyroidism grade 1 | Infusion related reaction grade 2 | Infusion site extravasation grade 2 | Injection site reaction grade 1 | Insomnia grade 1 | Localized edema grade 1 | Lymphedema grade 1 | Lymphocyte count decreased grade 1 | Lymphocyte count decreased grade 3 | Lymphocyte count decreased grade 4 | Mucositis oral grade 2 | Muscle weakness lower limb grade 1 | Musculoskeletal and connective tissue dis. grade 1 | Myalgia grade 1 | Nail discoloration grade 1 | Nail discoloration grade 2 | Nail loss grade 1 | Nail ridging grade 1 | Nasal congestion grade 1 | Nausea grade 1 | Nausea grade 2 | Nervous system disorders - Other grade 1 | Neutrophil count decreased grade 3 | Neutrophil count decreased grade 4 | Otitis externa grade 2 | Pain grade 1 | Pain in extremity grade 2 | Pelvic pain grade 1 | Penile infection grade 1 | Penile pain grade 1 | Peripheral sensory neuropathy grade 1 | Peripheral sensory neuropathy grade 2 | Platelet count decreased grade 1 | Rash acneiform grade 1 | Rash acneiform grade 2 | Rectal pain grade 1 | Renal and urinary disorders - Other grade 1 | Renal and urinary disorders - Other grade 2 | Respiratory, thoracic and mediastinal dis. grade 3 | Serum amylase increased grade 4 | Sinus disorder grade 1 | Sinusitis grade 2 | Skin and subcutaneous tissue disorders grade 1 | Skin and subcutaneous tissue disorders grade 2 | Skin infection grade 4 | Sore throat grade 1 | Thromboembolic event grade 3 | Toothache grade 1 | Tremor grade 1 | Upper respiratory infection grade 1 | Upper respiratory infection grade 2 | Upper respiratory infection grade 3 | Urinary frequency grade 1 | Urinary tract infection grade 2 | Urinary tract infection grade 3 | Urinary tract obstruction grade 2 | Vomiting grade 1 | Watering eyes grade 1 | Weight loss grade 1 | Weight loss grade 2 | Weight loss grade 3 | Wheezing grade 1 | White blood cell decreased grade 3 | White blood cell decreased grade 4 |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | 1 | 1 | 3 | 1 | 1 | 1 | 4 | 4 | 6 | 1 | 2 | 1 | 1 | 3 | 1 | 1 | 1 | 1 | 1 | 1 | 4 | 5 | 1 | 4 | 2 | 1 | 1 | 2 | 1 | 2 | 10 | 2 | 1 | 8 | 2 | 2 | 1 | 4 | 6 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 6 | 7 | 1 | 1 | 1 | 2 | 2 | 3 | 1 | 7 | 5 | 2 | 1 | 1 | 1 | 2 | 1 | 1 | 3 | 3 | 1 | 10 | 1 | 5 | 5 | 3 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 4 | 3 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 7 | 1 | 1 | 2 | 5 | 1 | 2 | 1 | 1 | 2 | 1 | 10 | 1 | 1 | 10 | 6 | 1 | 2 | 1 | 1 | 1 | 1 | 7 | 4 | 1 | 6 | 1 | 2 | 1 | 2 | 1 | 1 | 1 | 1 | 9 | 1 | 1 | 3 | 1 | 1 | 1 | 2 | 1 | 1 | 4 | 4 | 1 | 1 | 4 | 1 | 1 | 6 | 1 | 1 | 11 | 3 |
Measurements of Tumor Using Response Evaluation Criteria In Solid Tumors (RECIST) Criteria Before and After Treatment With the Combination of Pasireotide in Combination With Docetaxel
Percentage of participants responding to treatment by measurements of tumor using Response Evaluation Criteria In Solid Tumors (RECISTv1.0) 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, before and after treatment with the combination of pasireotide in combination with docetaxel (NCT01468532)
Timeframe: Every 12 weeks for the first 36 weeks and then every 16 weeks thereafter up to 100 weeks
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | 44.4 |
Overall Survival (OS)
Time from Treatment start date to date of death or last follow-up. (NCT01468532)
Timeframe: Every 3 months for the first 9 months on study then every 4 months after the first 9 months on study
| Intervention | months (Median) |
|---|
| Treatment (Chemotherapy, Receptor Agonist) | 18.3 |
PFS in Low-ERCC1 Participants
Progression-free survival is the length of time between protocol registration and disease progression or death, whichever occurs first. (NCT01498289)
Timeframe: Up to 3 years after registration
| Intervention | months (Median) |
|---|
| Arm I | 5.9 |
| Arm II | 2.8 |
PFS Variation by ERCC1
"Progression-free survival is the length of time between protocol registration and disease progression or death, whichever occurs first.~Participants were divided into subgroups according to ERCC1 quartiles to assess whether the differences in PFS between the two treatment arms varied by ERCC1 levels." (NCT01498289)
Timeframe: up to 3 years after registration
| Intervention | months (Median) |
|---|
| Q1 ERCC1 (0.20-0.80) | Q2 ERCC1 (0.81-1.10) | Q3 ERCC1 (1.11-1.42) | Q4 ERCC1 (1.43-5.71) |
|---|
| Arm I | 5.6 | 7.4 | 5.6 | 4.6 |
,| Arm II | 2.8 | 3.0 | 2.9 | 2.6 |
Overall Survival (OS)
OS is the length of time between protocol registration and patient death (NCT01498289)
Timeframe: Up to 3 years after registration
| Intervention | months (Median) |
|---|
| Arm I | 11.4 |
| Arm II | 8.7 |
Overall Response Rate (ORR)
"ORR (complete response, unconfirmed complete response, partial response, unconfirmed partial response) in patients with measurable disease were assessed in each arm and compared between arms using Chi-squared test.~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." (NCT01498289)
Timeframe: Up to 3 years after registration
| Intervention | percentage of evaluable participants (Number) |
|---|
| Arm I | 42 |
| Arm II | 30 |
Progression-free Survival (PFS) in High-ERCC1 Patients
Progression-free survival is the length of time between protocol registration and disease progression or death, whichever occurs first. (NCT01498289)
Timeframe: Up to 3 years after registration
| Intervention | months (Median) |
|---|
| Arm I FOLFOX | 4.7 |
| Arm II IT | 5.3 |
Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3
NCI-CTCAE version 4.03 was used to determine Gr, where Gr refers to severity of AE: Gr 1: mild; asymptomatic/mild symptoms; Gr 2: moderate; minimal; Gr 3: severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Creatinine Clearance(Chronic kidney disease) were based on: Gr 1: estimated glomerular filtration rate (eGFR) or creatinine clearance (CrCl) NCT01515748)
Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
| Intervention | Participants (Count of Participants) |
|---|
| Creatinine Clearance Gr 0 at Baseline to Gr >=3 | Creatinine Clearance Gr 1 at Baseline to Gr >=3 | Creatinine Clearance Gr 2 at Baseline to Gr >=3 | Creatinine Clearance Gr 3 at Baseline to Gr >=3 | Creatinine Clearance Gr 4 at Baseline to Gr >=3 | Creatinine Clearance Gr 5 at Baseline to Gr >=3 |
|---|
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAEs were defined as adverse events (AE) that appeared or worsened during the treatment period (up to 30 days after the last dose of the investigational product). SAE was an AE or adverse drug reaction at any dose of the investigational product that corresponded to one of the following: resulting in death or is life threatening; requiring in-patient hospitalization or prolongation of existing hospitalization; resulting in persistent or significant disability of dysfunction; resulting in congenital anomaly or birth defect; important medical event. (NCT01515748)
Timeframe: From randomization up to 30 days after last dose of study drug (maximum duration: up to 10 years)
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE | Any treatment emergent SAE | TEAEs leading to permanent discontinuation |
|---|
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 237 | 102 | 25 |
,| Surgery + Adjuvant Chemotherapy (SC) | 190 | 57 | 11 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. Analyzed using Kaplan-Meier method. (NCT01515748)
Timeframe: From randomization to date of death due to any cause (maximum duration: up to 10 years)
| Intervention | months (Median) |
|---|
| Surgery + Adjuvant Chemotherapy (SC) | NA |
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | NA |
Percentage of Participants With 3-Year Progression-Free Survival (PFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1
PFS was defined as the time from randomization to objective tumor progression, or recurrence or death. Progressive disease (PD) was defined as follows: 1) In Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) Arm, PD was determined according to the RECIST 1.1 Criteria during the neo-adjuvant chemotherapy period; 2) Irrespective of curative resection, if an intraoperative distant metastasis was observed or a distant metastasis was reported from pathology, it was considered PD; 3) If residual cancer cells were visually identified at the resection margin during surgery but could not be completely resected (R2), it was considered PD; 4) If residual cancer cells were finally confirmed at the resection margin during postoperative histology (R1), it was considered PD; 5) In case of finding a recurrence/distant metastasis or a new lesion during follow-up after R0 complete resection, it was defined as the first tumor assessment date when it was observed. (NCT01515748)
Timeframe: 3 years
| Intervention | percentage of participants (Number) |
|---|
| Surgery + Adjuvant Chemotherapy (SC) | 60.24 |
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 66.82 |
Percentage of Participants With R0 Resection
Tumor condition was explained according to the Residual Tumor (R) Classification: R0; No residual cancer (negative cross-section), R1; Microscopically observed residual cancer (positive cross-section), R2; Macroscopically observed residual cancer. (NCT01515748)
Timeframe: Up to 10 years
| Intervention | percentage of participants (Number) |
|---|
| Surgery + Adjuvant Chemotherapy (SC) | 83.74 |
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 95.50 |
Number of Participants With Post-Operative Pathological Stage Response
"TNM pathological stage was determined according to standardized histopathology and the American Joint Committee on Cancer (AJCC) staging system 7th Edition (Stages 0,IA,IB,IIA,IIB,IIIA,IIIB,IIIC and IV). Stage 0=carcinoma in situ with no metastatic potential; Stage IA=T1N0M0; Stage IB=T2N0M0,T1N1M0; Stage IIA=T3N0M0,T2N1M0,T1N2M0;Stage IIB=T4aN0M0,T3N1M0,T2N2M0,T1N3M0;Stage IIIA=T4aN1M0,T3N2M0,T2N3M0;Stage IIIB=T4bN0-1M0,T4aN2M0,T3N3M0;Stage IIIC=T4bN2-3M0, T4aN3M0 and Stage IV= distant metastases (M1) at diagnosis; where T denotes tumor size where T1: tumor invades lamina propria, muscularis mucosae, or submucosa; T2: invades muscularis propria; T3: invasion of subserosa; T4: T4a: penetrate serosa (visceral peritoneum) T4b: invade adjacent tissue and N denotes nodes affected where N1:1-2 positive lymph nodes; N2:3-6 positive lymph nodes; N3: 7 or more positive lymph nodes and M denotes metastases where M0: no distant metastases. Higher stages indicates worse outcome." (NCT01515748)
Timeframe: Up to 10 years
| Intervention | Participants (Count of Participants) |
|---|
| Stage 0 | Stage IA | Stage IB | Stage IIA | Stage IIB | Stage IIIA | Stage IIIB | Stage IIIC | Stage IV |
|---|
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 23 | 32 | 23 | 47 | 36 | 18 | 24 | 14 | 5 |
,| Surgery + Adjuvant Chemotherapy (SC) | 0 | 9 | 18 | 30 | 25 | 35 | 49 | 46 | 34 |
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3
NCI-CTCAE version 4.03 was used to determine Gr, where Gr refers to severity of AE: Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate; minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Aspartate and alanine aminotransferase increased were based on Gr1: >ULN-3.0*ULN; Gr2: >3.0-5.0*ULN; Gr3: >5.0-20.0*ULN; Gr4: >20.0*ULN. Blood bilirubin increased: Gr1: >ULN-1.5*ULN; Gr2 >1.5-3.0*ULN; Gr3: >3.0-10.0*ULN; Gr4: >10.0*ULN. Alkaline phosphatase increased: Gr1: >ULN-2.5*ULN; Gr2: >2.5-5.0*ULN; Gr3: >5.0-20.0*ULN; Gr4: >20.0*ULN. Glucose (Hypoglycemia): Gr 1: ULN-160 mg/dL; Gr2: Fasting glucose value >160-250 mg/dL; Gr3: >250-500 mg/dL; Gr4: >500 mg/dL; Gr5: Death. (NCT01515748)
Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
| Intervention | Participants (Count of Participants) |
|---|
| Aspartate aminotransferase Gr0 at Baseline toGr>=3 | Aspartate aminotransferase Gr1 at Baseline toGr>=3 | Aspartate aminotransferase Gr2 at Baseline toGr>=3 | Aspartate aminotransferase Gr3 at Baseline toGr>=3 | Aspartate aminotransferase Gr4 at Baseline toGr>=3 | Aspartate aminotransferase Gr5 at Baseline toGr>=3 | Alanine aminotransferase Gr0 at Baseline to Gr >=3 | Alanine aminotransferase Gr1 at Baseline to Gr >=3 | Alanine aminotransferase Gr2 at Baseline to Gr >=3 | Alanine aminotransferase Gr3 at Baseline to Gr >=3 | Alanine aminotransferase Gr4 at Baseline to Gr >=3 | Alanine aminotransferase Gr5 at Baseline to Gr >=3 | Bilirubin increased Gr 0 at Baseline to Gr >=3 | Bilirubin increased Gr 1 at Baseline to Gr >=3 | Bilirubin increased Gr 2 at Baseline to Gr >=3 | Bilirubin increased Gr 3 at Baseline to Gr >=3 | Bilirubin increased Gr 4 at Baseline to Gr >=3 | Bilirubin increased Gr 5 at Baseline to Gr >=3 | Alkaline phosphatase Gr 0 at Baseline to Gr >=3 | Alkaline phosphatase Gr 1 at Baseline to Gr >=3 | Alkaline phosphatase Gr 2 at Baseline to Gr >=3 | Alkaline phosphatase Gr 3 at Baseline to Gr >=3 | Alkaline phosphatase Gr 4 at Baseline to Gr >=3 | Alkaline phosphatase Gr 5 at Baseline to Gr >=3 | Hypoglycemia Gr 0 at Baseline to Gr >=3 | Hypoglycemia Gr 1 at Baseline to Gr >=3 | Hypoglycemia Gr 2 at Baseline to Gr >=3 | Hypoglycemia Gr 3 at Baseline to Gr >=3 | Hypoglycemia Gr 4 at Baseline to Gr >=3 | Hypoglycemia Gr 5 at Baseline to Gr >=3 | Hyperglycemia Gr 0 at Baseline to Gr >=3 | Hyperglycemia Gr 1 at Baseline to Gr >=3 | Hyperglycemia Gr 2 at Baseline to Gr >=3 | Hyperglycemia Gr 3 at Baseline to Gr >=3 | Hyperglycemia Gr 4 at Baseline to Gr >=3 | Hyperglycemia Gr 5 at Baseline to Gr >=3 |
|---|
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 12 | 13 | 10 | 2 | 0 | 0 |
,| Surgery + Adjuvant Chemotherapy (SC) | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 4 | 1 | 1 | 0 | 0 | 0 | 4 | 13 | 2 | 3 | 0 | 0 |
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3
NCI-CTCAE version 4.03 was used to determine Gr,where Gr refers to severity of AE:Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate;minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Calcium(Hypocalcemia) were based on Gr1: Corrected serum calcium of ULN -11.5 mg/dL; Gr2: Corrected serum calcium of >11.5-12.5 mg/dL; Gr3: Corrected serum calcium of >12.5-13.5 mg/dL; Gr4: Corrected serum calcium of >13.5 mg/dL;Gr5:Death. Creatinine increased: Gr 1: >1-1.5*baseline; >ULN-1.5*ULN; Gr2: >1.5-3.0*baseline; >1.5-3.0*ULN; Gr3: >3.0 baseline; >3.0-6.0*ULN; Gr4: >6.0 x ULN. Albumin(Hypoalbuminemia): Gr 1: NCT01515748)
Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
| Intervention | Participants (Count of Participants) |
|---|
| Hypocalcemia Gr 0 at Baseline to Gr >=3 | Hypocalcemia Gr 1 at Baseline to Gr >=3 | Hypocalcemia Gr 2 at Baseline to Gr >=3 | Hypocalcemia Gr 3 at Baseline to Gr >=3 | Hypocalcemia Gr 4 at Baseline to Gr >=3 | Hypocalcemia Gr 5 at Baseline to Gr >=3 | Hypercalcemia Gr 0 at Baseline to Gr >=3 | Hypercalcemia Gr 1 at Baseline to Gr >=3 | Hypercalcemia Gr 2 at Baseline to Gr >=3 | Hypercalcemia Gr 3 at Baseline to Gr >=3 | Hypercalcemia Gr 4 at Baseline to Gr >=3 | Hypercalcemia Gr 5 at Baseline to Gr >=3 | Creatinine increased Gr 0 at Baseline to Gr >=3 | Creatinine increased Gr 1 at Baseline to Gr >=3 | Creatinine increased Gr 2 at Baseline to Gr >=3 | Creatinine increased Gr 3 at Baseline to Gr >=3 | Creatinine increased Gr 4 at Baseline to Gr >=3 | Creatinine increased Gr 5 at Baseline to Gr >=3 | Hypoalbuminemia Gr 0 at Baseline to Gr >=3 | Hypoalbuminemia Gr 1 at Baseline to Gr >=3 | Hypoalbuminemia Gr 2 at Baseline to Gr >=3 | Hypoalbuminemia Gr 3 at Baseline to Gr >=3 | Hypoalbuminemia Gr 4 at Baseline to Gr >=3 | Hypoalbuminemia Gr 5 at Baseline to Gr >=3 |
|---|
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 8 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 |
,| Surgery + Adjuvant Chemotherapy (SC) | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3
NCI-CTCAE version 4.03 was used to determine Grade(Gr),where Gr refers to severity of AE:Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate;minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Hemoglobin(Hb)(Anemia) were based on Gr1:0-2g/dL above upper limit of normal(ULN);Gr2: incr. in >2-4g/dL above ULN; Gr3:incr. in >4gm/dL above ULN. White blood cell (WBC) decreased: Gr1:100,000/mm^3, Gr4:clinical manifestations of leucostasis;Gr5:Death. Abnormal Neutrophil count (ANC):- Gr1:NCT01515748)
Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
| Intervention | Participants (Count of Participants) |
|---|
| Hb(Anemia) Gr 0 at Baseline to Gr >=3 | Hb(Anemia) Gr 1 at Baseline to Gr >=3 | Hb(Anemia) Gr 2 at Baseline to Gr >=3 | Hb(Anemia) Gr 3 at Baseline to Gr >=3 | Hb(Anemia) Gr 4 at Baseline to Gr >=3 | Hb(Anemia) Gr 5 at Baseline to Gr >=3 | Hb increased Gr 0 at Baseline to Gr >=3 | Hb increased Gr 1 at Baseline to Gr >=3 | Hb increased Gr 2 at Baseline to Gr >=3 | Hb increased Gr 3 at Baseline to Gr >=3 | Hb increased Gr 4 at Baseline to Gr >=3 | Hb increased Gr 5 at Baseline to Gr >=3 | WBC decreased Gr 0 at Baseline to Gr >=3 | WBC decreased Gr 1 at Baseline to Gr >=3 | WBC decreased Gr 2 at Baseline to Gr >=3 | WBC decreased Gr 3 at Baseline to Gr >=3 | WBC decreased Gr 4 at Baseline to Gr >=3 | WBC decreased Gr 5 at Baseline to Gr >=3 | WBC (Leukocytosis) Gr 0 at Baseline to Gr >=3 | WBC (Leukocytosis) Gr 1 at Baseline to Gr >=3 | WBC (Leukocytosis) Gr 2 at Baseline to Gr >=3 | WBC (Leukocytosis) Gr 3 at Baseline to Gr >=3 | WBC (Leukocytosis) Gr 4 at Baseline to Gr >=3 | WBC (Leukocytosis) Gr 5 at Baseline to Gr >=3 | ANC Gr 0 at Baseline to Gr >=3 | ANC Gr 1 at Baseline to Gr >=3 | ANC Gr 2 at Baseline to Gr >=3 | ANC Gr 3 at Baseline to Gr >=3 | ANC Gr 4 at Baseline to Gr >=3 | ANC Gr 5 at Baseline to Gr >=3 | Platelet count decreased Gr0 at Baseline to Gr >=3 | Platelet count decreased Gr1 at Baseline to Gr >=3 | Platelet count decreased Gr2 at Baseline to Gr >=3 | Platelet count decreased Gr3 at Baseline to Gr >=3 | Platelet count decreased Gr4 at Baseline to Gr >=3 | Platelet count decreased Gr5 at Baseline to Gr >=3 |
|---|
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 0 | 4 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 40 | 0 | 0 | 0 | 0 | 0 | 5 | 0 | 0 | 0 | 0 | 0 |
,| Surgery + Adjuvant Chemotherapy (SC) | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 14 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3
NCI-CTCAE version 4.03 was used to determine Gr,where Gr refers to severity of AE: Gr 1: mild; asymptomatic/mild symptoms; Gr 2: moderate; minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Sodium (Hyponatremia) were based on Gr1: ULN-150 mmol/L; Gr2: >150-155 mmol/L; Gr3:>155-160 mmol/L;hospitalization; Gr4: >160 mmol/L; life-threatening consequences; Gr5: Death. Potassium (Hypokalemia): Gr 1: ULN-5.5 mmol/L; Gr2: >5.5-6.0 mmol/L; Gr3: >6.0-7.0 mmol/L; hospitalization indicated; Gr4: >7.0 mmol/L; life-threatening consequences; Gr5: Death. (NCT01515748)
Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)
| Intervention | Participants (Count of Participants) |
|---|
| Hyponatremia Gr 0 at Baseline to Gr >=3 | Hyponatremia Gr 1 at Baseline to Gr >=3 | Hyponatremia Gr 2 at Baseline to Gr >=3 | Hyponatremia Gr 3 at Baseline to Gr >=3 | Hyponatremia Gr 4 at Baseline to Gr >=3 | Hyponatremia Gr 5 at Baseline to Gr >=3 | Hypernatremia Gr 0 at Baseline to Gr >=3 | Hypernatremia Gr 1 at Baseline to Gr >=3 | Hypernatremia Gr 2 at Baseline to Gr >=3 | Hypernatremia Gr 3 at Baseline to Gr >=3 | Hypernatremia Gr 4 at Baseline to Gr >=3 | Hypernatremia Gr 5 at Baseline to Gr >=3 | Hypokalemia Gr 0 at Baseline to Gr >=3 | Hypokalemia Gr 1 at Baseline to Gr >=3 | Hypokalemia Gr 2 at Baseline to Gr >=3 | Hypokalemia Gr 3 at Baseline to Gr >=3 | Hypokalemia Gr 4 at Baseline to Gr >=3 | Hypokalemia Gr 5 at Baseline to Gr >=3 | Hyperkalemia Gr 0 at Baseline to Gr >=3 | Hyperkalemia Gr 1 at Baseline to Gr >=3 | Hyperkalemia Gr 2 at Baseline to Gr >=3 | Hyperkalemia Gr 3 at Baseline to Gr >=3 | Hyperkalemia Gr 4 at Baseline to Gr >=3 | Hyperkalemia Gr 5 at Baseline to Gr >=3 |
|---|
| Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) | 7 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 0 | 0 |
,| Surgery + Adjuvant Chemotherapy (SC) | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Pathologic Complete Response (pCR) Rate in Patients Treated With ErC for 6 Cycles Prior to Surgery
One cycle = 21 days. Pathologic CR is defined as the absence of invasive tumor in the breast and lymph node tissue removed at the time of definitive surgery as judged by the local pathologist. (NCT01527487)
Timeframe: 18 weeks
| Intervention | percentage of surgical patients (Number) |
|---|
| Eribulin+Cyclophosphamide (ErC) | 18 |
| Docetaxel+Cyclophosphamide (TC) | 10 |
The Number of Adverse Events as a Measure of Safety and Tolerability.
Treatment-Related Adverse Events occurring in >= 15% of treated patients (NCT01527487)
Timeframe: 43 months
| Intervention | participants (Number) |
|---|
| Fatigue | Alopecia | Nausea | Peripheral Sensory Neuropathy | Neutrophil Count Decreased | Constipation | Diarrhea | Anemia | Headache | Dysgeusia | White Blood Cell Decreased | Myalgia | Hot Flashes | Mucositis | Arthralgia | Edema Limbs |
|---|
| Docetaxel+Cyclophosphamide (TC) | 14 | 14 | 8 | 10 | 6 | 6 | 10 | 8 | 4 | 5 | 5 | 6 | 3 | 5 | 8 | 8 |
,| Eribulin+Cyclophosphamide (ErC) | 32 | 25 | 26 | 18 | 21 | 15 | 11 | 12 | 9 | 8 | 8 | 7 | 7 | 5 | 2 | 2 |
Disease-Free Survival (DFS) at 2 Years
Defined as the percent probability that participants had not experienced disease recurrence or died from any cause at 2 years post-surgery, analyzed by Kaplan-Meier methodology. (NCT01527487)
Timeframe: 24 months
| Intervention | percent probability of survival (Number) |
|---|
| Eribulin+Cyclophosphamide (ErC) | 82.35 |
| Docetaxel+Cyclophosphamide (TC) | 89.06 |
Clinical Response Rate (cRR) of ErC as Neoadjuvant Therapy
Defined as the number of patients with a best response of clinical complete or partial response (cCR or cPR) divided by the number of patients qualified for tumor response analysis per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) v1.1 for target lesions and assessed by MRI or CT. Complete Response (CR) defined as disappearance of all target lesions; Partial Response (PR) defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD; (NCT01527487)
Timeframe: 43 months
| Intervention | percentage of participants (Number) |
|---|
| Eribulin+Cyclophosphamide (ErC) | 67.6 |
| Docetaxel+Cyclophosphamide (TC) | 64.7 |
Number of Participants With Recurrence
The duration of time from study entry to time of recurrence or death, whichever occurred first, or the date of last contact. (NCT01533207)
Timeframe: Follow-up every 4 months for 3 years, then every 6 months for 2 years.
| Intervention | participants (Number) |
|---|
| Regimen 1 | 8 |
| Regimen II | 8 |
Number of Participants Who Experienced Death
The duration of time from study entry to time of death or the date of last contact. (NCT01533207)
Timeframe: Follow-up every 4 months for 3 years, then every 6 months for 2 years.
| Intervention | Participants (Number) |
|---|
| Regimen 1 | 5 |
| Regimen II | 1 |
Incidence of Grade 3 or Higher Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
(NCT01533207)
Timeframe: Approximately 4 years
| Intervention | participants (Number) |
|---|
| Regimen 1 | 10 |
| Regimen II | 1 |
Time to Progression
Determined using RECIST. Estimated using the Kaplan-Meier method. Log-rank tests will be used to test for differences and Cox proportional hazards regression modeling will be used to adjust for patient demographics and characteristics such as smoking status at baseline (actively/non-actively smoking). Progression is 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. (NCT01557959)
Timeframe: 2 years
| Intervention | months (Median) |
|---|
| Treatment (Chemo, Chemoprotection, Antiangiogenesis Therapy) | 4.63 |
Response Rate Among Subgroups of Patients According to Molecular Profiles Including Tumor Characteristics and Genetic Polymorphisms From Peripheral Blood
"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. Pre-specified that data is only presented for the subgroups Low Cyclin D1 and High Cyclin D1." (NCT01557959)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Progressive disease | Stable disease | Partial response |
|---|
| High Cyclin D1 | 4 | 9 | 2 |
,| Low Cyclin D1 | 3 | 9 | 4 |
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 2
(NCT01567163)
Timeframe: Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion
| Intervention | nanograms/milliliter/milligram (Geometric Mean) |
|---|
| Docetaxel (Cycle 2) | 8.78 |
Pharmacokinetics: Maximum Observed Drug Concentration (Cmax) of Ramucirumab in the Presence of Docetaxel
(NCT01567163)
Timeframe: Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion
| Intervention | micrograms/milliliter (mcg/mL) (Geometric Mean) |
|---|
| Ramucirumab | 303.6 |
Number of Participants With Treatment-Emergent Anti-Ramucirumab Antibodies
Participants with treatment-emergent anti-ramucirumab antibodies were participants with a 4-fold increase (2 dilution increase) in immunogenicity titer over baseline titer, or participants who tested negative at baseline and positive post-baseline (at titer of ≥1:20). (NCT01567163)
Timeframe: Cycle 1, Day 1 through Cycle 2, Day 1 and 30 days after last dose of study drug
| Intervention | participants (Number) |
|---|
| Immunogenicity During Study (n=17) | Immunogenicity Post-Treatment (n=5) |
|---|
| All Participants | 0 | 0 |
Pharmacokinetics: Area Under the Concentration Versus Time Curve of Ramucirumab From Time Zero to Infinity [AUC(0-∞)] in the Presence of Docetaxel
(NCT01567163)
Timeframe: Cycle 2: 1 hour prior to ramucirumab infusion, 0, 1, 2, 2.5, 3, 4, 6, 8, 25, 49, 73, 169, 265 and 337 hours post ramucirumab infusion
| Intervention | micrograms*hour/milliliter (mcg*h/mL) (Geometric Mean) |
|---|
| Ramucirumab | 42400 |
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 1
(NCT01567163)
Timeframe: Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion
| Intervention | nanograms*hour/milliliter/milligram (Geometric Mean) |
|---|
| Docetaxel (Cycle 1) | 13.7 |
Pharmacokinetics: Dose-Normalized Area Under the Concentration Versus Time Curve of Docetaxel From Time Zero to Infinity [AUC(0-∞)] Following a Single Dose in Cycle 2
(NCT01567163)
Timeframe: Cycle 2: 0, 1, 1.5, 2, 3, 5, 7, 24, 48 and 72 hours post docetaxel infusion
| Intervention | nanograms*hour/milliliter/milligram (Geometric Mean) |
|---|
| Docetaxel (Cycle 2) | 12.8 |
Pharmacokinetics: Dose-Normalized Maximum Observed Drug Concentration (Cmax) of Docetaxel in Cycle 1
(NCT01567163)
Timeframe: Cycle 1: 0, 1, 1.5, 2, 3, 5, 7, 24, 48, and 72 hours post docetaxel infusion
| Intervention | nanograms/milliliter/milligram (Geometric Mean) |
|---|
| Docetaxel (Cycle 1) | 7.66 |
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Values Over the Course of the Study
All participants must have had a baseline LVEF ≥50% to enroll in the study; patients with significant cardiac disease or baseline LVEF below 50% were not eligible for this study. The change from baseline LVEF values were reported at every 3 cycles over the course of the study and at the final treatment, worst treatment, and maximum decrease values. The final treatment value was defined as the last LVEF value observed before all study treatment discontinuation. The worst treatment value was defined as the lowest LVEF value observed before all study treatment discontinuation. The maximum decrease value was defined as the largest decrease of LVEF value from baseline, or minimum increase if a participant's post-baseline LVEF measures were all larger than the baseline value. (NCT01572038)
Timeframe: Baseline, predose on Day 1 of every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Percentage points of LVEF (Mean) |
|---|
| Baseline (BL): Absolute Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Cycle 54 | Change from BL at Cycle 57 | Change from BL at Cycle 60 | Change from BL at Cycle 63 | Change from BL at Cycle 66 | Change from BL at Cycle 69 | Change from BL at Cycle 72 | Change from BL at Cycle 75 | Change from BL at Cycle 78 | Change from BL at Cycle 81 | Change from BL at Cycle 84 | Change from BL at Cycle 87 | Change from BL at Cycle 90 | Change from BL at Cycle 93 | Change from BL at Cycle 96 | Change from BL at Cycle 99 | Change from BL at Cycle 102 | Change from BL at Cycle 105 | Change from BL at Cycle 108 | Change from BL at Cycle 111 | Change from BL at Cycle 114 | Change from BL at Cycle 117 | Change from BL at Cycle 120 | Change from BL at Cycle 123 | Change from BL at Cycle 126 | Change from BL at End of Treatment | Change from BL at Day 28 of Follow-Up | Change from BL: Final Treatment Value | Change from BL: Worst Treatment Value | Change from BL: Maximum Decrease Value |
|---|
| Pertuzumab + Trastuzumab + Taxane | 64.6 | -1.1 | -1.5 | -2.1 | -1.9 | -2.2 | -1.8 | -1.9 | -1.9 | -2.1 | -1.8 | -1.9 | -2.1 | -2.1 | -1.9 | -2.2 | -2.1 | -1.6 | -1.7 | -1.7 | -1.5 | -1.6 | -2.0 | -1.9 | -2.1 | -1.5 | -1.8 | -1.8 | -1.6 | -1.9 | -1.1 | -1.6 | -1.8 | -2.0 | -2.5 | -2.5 | -1.8 | -3.3 | -1.1 | -5.8 | -8.6 | -9.3 | -9.0 | -3.8 | -3.2 | -2.0 | -7.1 | -7.7 |
Number of Participants Who Died Over the Course of the Study by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term)
All adverse events leading to death, regardless of whether they were classified as treatment emergent, are listed by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities, version 22.1 (MedDRA version 22.1); PTs that are part of a given SOC are listed in the rows directly below each SOC within the results table. Admin. = administration; Mediast. = mediastinal (NCT01572038)
Timeframe: The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Participants (Count of Participants) |
|---|
| Total Number of Deaths | Number of Deaths by Cause: Progressive Disease | Number of Deaths by Cause: Other | Number of Deaths by Cause: Adverse Event (Total) | Infections and Infestations (SOC) | Peritonitis (PT) | Pneumonia (PT) | Respiratory Tract Infection (PT) | Sepsis (PT) | Septic Shock (PT) | Cardiac Disorders (SOC) | Cardiac Arrest (PT) | Cardiac Failure (PT) | Cardiac Failure Congestive (PT) | Cardio-respiratory Arrest (PT) | Myocardial Infarction (PT) | Right Ventricular Failure (PT) | General Disorders & Admin. Site Conditions (SOC) | Death (PT) | Blood and Lymphatic System Disorders (SOC) | Febrile Neutropenia (PT) | Neutropenia (PT) | Thrombocytopenia (PT) | Respiratory, Thoracic & Mediast. Disorders (SOC) | Acute Respiratory Distress Syndrome (PT) | Aspiration (PT) | Pneumonitis (PT) | Gastrointestinal Disorders (SOC) | Pancreatitis (PT) | Pancreatitis Chronic (PT) | Nervous System Disorders (SOC) | Hepatic Encephalopathy (PT) | Ischemic Stroke (PT) | Metabolism and Nutrition Disorders (SOC) | Hypoglycaemia (PT) | Hepatobiliary Disorders (SOC) | Hepatic Failure (PT) | Psychiatric Disorders (SOC) | Delirium (PT) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 658 | 581 | 42 | 35 | 11 | 1 | 5 | 1 | 3 | 1 | 7 | 2 | 1 | 1 | 1 | 1 | 1 | 6 | 6 | 3 | 1 | 1 | 1 | 3 | 1 | 1 | 1 | 2 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Number of Participants Who Died Within 6 Months of Starting Study Treatment by Reported Cause of Death (Adverse Events Leading to Death by System Organ Class and Preferred Term)
All adverse events leading to death, regardless of whether they were classified as treatment emergent, are listed by system organ class (SOC) and preferred term (PT) according to the Medical Dictionary for Regulatory Activities, version 22.1 (MedDRA version 22.1); PTs that are part of a given SOC are listed in the rows directly below each SOC within the results table. Admin. = administration; Mediast. = mediastinal (NCT01572038)
Timeframe: The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Participants (Count of Participants) |
|---|
| Total Number of Deaths | Number of Deaths by Cause: Progressive Disease | Number of Deaths by Cause: Other | Number of Deaths by Cause: Adverse Event (Total) | Infections and Infestations (SOC) | Peritonitis (PT) | Pneumonia (PT) | Respiratory Tract Infection (PT) | Sepsis (PT) | General Disorders & Admin. Site Conditions (SOC) | Death (PT) | Blood and Lymphatic System Disorders (SOC) | Febrile Neutropenia (PT) | Neutropenia (PT) | Thrombocytopenia (PT) | Cardiac Disorders (SOC) | Cardiac Arrest (PT) | Cardio-Respiratory Arrest (PT) | Respiratory, Thoracic & Mediast. Disorders (SOC) | Acute Respiratory Distress Syndrome (PT) | Pneumonitis (PT) | Gastrointestinal Disorders (SOC) | Pancreatitis (PT) | Nervous System Disorders (SOC) | Hepatic Encephalopathy (PT) | Metabolism and Nutrition Disorders (SOC) | Hypoglycaemia (PT) | Hepatobiliary Disorders (SOC) | Hepatic Failure (PT) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 38 | 18 | 1 | 19 | 6 | 1 | 2 | 1 | 2 | 4 | 4 | 3 | 1 | 1 | 1 | 2 | 1 | 1 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events to Monitor, Occurring in ≥0.5% of Participants by Category and Preferred Term
Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first dose of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, it was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. If a participant had more than one event in a category, they were counted only once in that category. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent. MedDRA version 22.1 was used to code AEs; preferred terms (PT) that are part of a given category are listed in the rows directly below each category within the results table. (NCT01572038)
Timeframe: From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Any Grade ≥3 TEAE to Monitor | Neutropenia/Febrile Neutropenia (Category) | Neutropenia (PT) | Febrile Neutropenia (PT) | Neutrophil Count Decreased (PT) | Leukopenia (PT) | White Blood Cell Count Decreased (PT) | Neutropenic Sepsis (PT) | Infusion-/Admin.-Related Reactions (Category) | Hypertension (PT) | IRR/ARR: Drug Hypersensitivity (PT) | Asthenia (PT) | Fatigue (PT) | Dyspnoea (PT) | Infusion Related Reaction (PT) | Paraesthesia (PT) | Diarrhoea Grade ≥3 (Category) | Diarrhoea (PT) | Cardiac Dysfunction (Category) | Ejection Fraction Decreased (PT) | Left Ventricular Dysfunction (PT) | Cardiac Failure (PT) | Mucositis (Category) | Mucosal Inflammation (PT) | Stomatitis (PT) | Rash/Skin Reactions (Category) | Rash (PT) | Anaphylaxis and Hypersensitivity (Category) | Anaphyl./Hypersens.: Drug Hypersensitivity (PT) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 535 | 279 | 145 | 90 | 38 | 18 | 18 | 10 | 123 | 27 | 12 | 11 | 11 | 10 | 8 | 7 | 120 | 120 | 51 | 24 | 11 | 9 | 33 | 14 | 9 | 28 | 10 | 18 | 13 |
Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria
Clinical laboratory tests for biochemistry parameters were performed at local laboratories. Laboratory toxicities were defined based on local laboratory normal ranges (for parameters with NCI-CTC grade not defined). Some laboratory parameters are bi-dimensional (i.e. can be graded in both the low and high direction). These parameters were split and presented in both directions. Baseline was defined as the last non-missing measurement taken prior to the first dose of study treatment (including unscheduled assessments). Values from all visits, including unscheduled visits, were included in the derivation of the worst post-baseline grade. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: was clinically significant (per investigator); was accompanied by clinical symptoms; resulted in a change in study treatment; or resulted in a medical intervention or a change in concomitant therapy. (NCT01572038)
Timeframe: Predose at each treatment cycle (1 cycle is 3 weeks) from Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Blood Urea Nitrogen (High): Normal to Normal | Blood Urea Nitrogen (High): Normal to Low | Blood Urea Nitrogen (High): Normal to High | Blood Urea Nitrogen (High): Normal to Missing | Blood Urea Nitrogen (High): Low to Normal | Blood Urea Nitrogen (High): Low to Low | Blood Urea Nitrogen (High): Low to High | Blood Urea Nitrogen (High): High to Normal | Blood Urea Nitrogen (High): High to High | Blood Urea Nitrogen (High): Missing to Normal | Blood Urea Nitrogen (High): Missing to High | Blood Urea Nitrogen (High): Missing to Missing | Blood Urea Nitrogen (Low): Normal to Normal | Blood Urea Nitrogen (Low): Normal to Low | Blood Urea Nitrogen (Low): Normal to High | Blood Urea Nitrogen (Low): Normal to Missing | Blood Urea Nitrogen (Low): Low to Normal | Blood Urea Nitrogen (Low): Low to Low | Blood Urea Nitrogen (Low): High to Normal | Blood Urea Nitrogen (Low): High to Low | Blood Urea Nitrogen (Low): High to High | Blood Urea Nitrogen (Low): Missing to Normal | Blood Urea Nitrogen (Low): Missing to Low | Blood Urea Nitrogen (Low): Missing to High | Blood Urea Nitrogen (Low): Missing to Missing | Calc Creatinine Clearance (High): Normal to Normal | Calc Creatinine Clearance (High): Normal to Low | Calc Creatinine Clearance (High): Normal to High | Calc Creatinine Clearance(High): Normal to Missing | Calc Creatinine Clearance (High): Low to Normal | Calc Creatinine Clearance (High): Low to Low | Calc Creatinine Clearance (High): Low to High | Calc Creatinine Clearance (High): Low to Missing | Calc Creatinine Clearance (High): High to Normal | Calc Creatinine Clearance (High): High to High | Calc Creatinine Clearance(High): Missing to Normal | Calc Creatinine Clearance (High): Missing to Low | Calc Creatinine Clearance (High): Missing to High | Calc Creatinine Clearance(High):Missing to Missing | Calc Creatinine Clearance (Low): Normal to Normal | Calc Creatinine Clearance (Low): Normal to Low | Calc Creatinine Clearance (Low): Normal to High | Calc Creatinine Clearance (Low): Low to Normal | Calc Creatinine Clearance (Low): Low to Low | Calc Creatinine Clearance (Low): Low to High | Calc Creatinine Clearance (Low): Low to Missing | Calc Creatinine Clearance (Low): High to Normal | Calc Creatinine Clearance (Low): High to Low | Calc Creatinine Clearance (Low): High to High | Calc Creatinine Clearance (Low): Missing to Normal | Calc Creatinine Clearance (Low): Missing to Low | Calc Creatinine Clearance (Low): Missing to High | Calc Creatinine Clearance(Low): Missing to Missing | Chloride (High): Normal to Normal | Chloride (High): Normal to Low | Chloride (High): Normal to High | Chloride (High): Low to Normal | Chloride (High): Low to High | Chloride (High): High to Normal | Chloride (High): High to High | Chloride (High): Missing to Normal | Chloride (High): Missing to High | Chloride (High): Missing to Missing | Chloride (Low): Normal to Normal | Chloride (Low): Normal to Low | Chloride (Low): Normal to High | Chloride (Low): Low to Normal | Chloride (Low): Low to Low | Chloride (Low): High to Normal | Chloride (Low): High to Low | Chloride (Low): High to High | Chloride (Low): Missing to Normal | Chloride (Low): Missing to Low | Chloride (Low): Missing to High | Chloride (Low): Missing to Missing | Lactate Dehydrogenase (High): Normal to Normal | Lactate Dehydrogenase (High): Normal to High | Lactate Dehydrogenase (High): Low to Normal | Lactate Dehydrogenase (High): Low to Low | Lactate Dehydrogenase (High): Low to High | Lactate Dehydrogenase (High): High to Normal | Lactate Dehydrogenase (High): High to High | Lactate Dehydrogenase (High): Missing to Normal | Lactate Dehydrogenase (High): Missing to High | Lactate Dehydrogenase (High): Missing to Missing | Lactate Dehydrogenase (Low): Normal to Normal | Lactate Dehydrogenase (Low): Normal to Low | Lactate Dehydrogenase (Low): Normal to High | Lactate Dehydrogenase (Low): Low to Normal | Lactate Dehydrogenase (Low): Low to Low | Lactate Dehydrogenase (Low): Low to High | Lactate Dehydrogenase (Low): High to Normal | Lactate Dehydrogenase (Low): High to Low | Lactate Dehydrogenase (Low): High to High | Lactate Dehydrogenase (Low): Missing to Normal | Lactate Dehydrogenase (Low): Missing to Low | Lactate Dehydrogenase (Low): Missing to High | Lactate Dehydrogenase (Low): Missing to Missing | Total Protein (High): Normal to Normal | Total Protein (High): Normal to Low | Total Protein (High): Normal to High | Total Protein (High): Low to Normal | Total Protein (High): Low to Low | Total Protein (High): High to Normal | Total Protein (High): High to High | Total Protein (High): Missing to Normal | Total Protein (High): Missing to Low | Total Protein (High): Missing to High | Total Protein (High): Missing to Missing | Total Protein (Low): Normal to Normal | Total Protein (Low): Normal to Low | Total Protein (Low): Low to Normal | Total Protein (Low): Low to Low | Total Protein (Low): High to Normal | Total Protein (Low): High to Low | Total Protein (Low): Missing to Normal | Total Protein (Low): Missing to Low | Total Protein (Low): Missing to Missing |
|---|
| Pertuzumab + Trastuzumab + Taxane | 717 | 5 | 402 | 2 | 69 | 8 | 12 | 23 | 98 | 42 | 19 | 39 | 828 | 293 | 3 | 2 | 17 | 72 | 104 | 11 | 6 | 47 | 11 | 3 | 39 | 540 | 11 | 201 | 2 | 166 | 107 | 34 | 1 | 13 | 101 | 46 | 8 | 11 | 195 | 393 | 353 | 8 | 12 | 294 | 1 | 1 | 61 | 36 | 17 | 66 | 44 | 17 | 133 | 665 | 2 | 508 | 54 | 13 | 4 | 58 | 41 | 32 | 59 | 971 | 201 | 3 | 31 | 36 | 57 | 4 | 1 | 60 | 13 | 1 | 58 | 328 | 499 | 10 | 1 | 4 | 74 | 449 | 16 | 30 | 25 | 716 | 102 | 9 | 5 | 9 | 1 | 426 | 31 | 66 | 39 | 3 | 3 | 26 | 1091 | 20 | 110 | 72 | 14 | 28 | 24 | 38 | 3 | 4 | 32 | 530 | 691 | 4 | 82 | 41 | 11 | 23 | 23 | 31 |
Change From Baseline in FACT-B Questionnaire Breast Cancer Subscale Score Over the Course of the Study
The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the breast cancer subscale, participants were given a series of 10 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B breast cancer subscale score, ranging from 0 to 40, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only. (NCT01572038)
Timeframe: Baseline, every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Score on a scale (Mean) |
|---|
| Baseline (BL): Absolute Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Cycle 54 | Change from BL at Cycle 57 | Change from BL at Cycle 60 | Change from BL at Cycle 63 | Change from BL at Cycle 66 | Change from BL at Cycle 69 | Change from BL at Cycle 72 | Change from BL at Cycle 75 | Change from BL at Cycle 78 | Change from BL at Cycle 81 | Change from BL at Cycle 84 | Change from BL at Cycle 87 | Change from BL at Cycle 90 | Change from BL at Cycle 93 | Change from BL at Cycle 96 | Change from BL at Cycle 99 | Change from BL at Cycle 102 | Change from BL at Cycle 105 | Change from BL at Cycle 108 | Change from BL at Cycle 111 | Change from BL at Cycle 114 | Change from BL at Cycle 117 | Change from BL at Cycle 120 | Change from BL at Cycle 123 | Change from BL at End of Treatment | Change from BL at Day 28 of Follow-Up |
|---|
| Pertuzumab + Trastuzumab + Taxane | 24.98 | 0.48 | -0.11 | 0.52 | 0.89 | 1.16 | 1.30 | 1.30 | 1.39 | 1.17 | 1.34 | 1.34 | 1.33 | 1.12 | 1.11 | 1.13 | 1.00 | 0.99 | 0.76 | 0.70 | 0.80 | 1.32 | 0.74 | 0.54 | 0.50 | 0.85 | 1.22 | 0.27 | 0.55 | 1.17 | 0.51 | 0.30 | 0.65 | 1.19 | 0.56 | 0.68 | 0.19 | 0.01 | -1.67 | -1.56 | -2.17 | -7.94 | 0.88 | 0.66 |
Number of Participants With Laboratory Abnormalities in Biochemistry Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0
Clinical laboratory tests for biochemistry parameters were performed at local laboratories. Laboratory toxicities were defined based on NCI-CTC v4.0 from Grades 1 (least severe) to 4 (most severe). Some laboratory parameters are bi-dimensional (i.e. can be graded in both the low and high direction). These parameters were split and presented in both directions. Baseline was defined as the last non-missing measurement taken prior to the first dose of study treatment (including unscheduled assessments). Values from all visits, including unscheduled visits, were included in the derivation of the worst post-baseline grade. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: was clinically significant (per investigator); was accompanied by clinical symptoms; resulted in a change in study treatment; or resulted in a medical intervention or a change in concomitant therapy. (NCT01572038)
Timeframe: Predose at each treatment cycle (1 cycle is 3 weeks) from Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Alanine Aminotransferase: Normal to Normal | Alanine Aminotransferase: Normal to Grade 1 | Alanine Aminotransferase: Normal to Grade 2 | Alanine Aminotransferase: Normal to Grade 3 | Alanine Aminotransferase: Normal to Missing | Alanine Aminotransferase: Grade 1 to Normal | Alanine Aminotransferase: Grade 1 to 1 | Alanine Aminotransferase: Grade 1 to 2 | Alanine Aminotransferase: Grade 1 to 3 | Alanine Aminotransferase: Grade 1 to Missing | Alanine Aminotransferase: Grade 2 to Normal | Alanine Aminotransferase: Grade 2 to 1 | Alanine Aminotransferase: Grade 2 to 2 | Alanine Aminotransferase: Grade 2 to 3 | Alanine Aminotransferase: Grade 3 to 1 | Alanine Aminotransferase: Missing to Normal | Alanine Aminotransferase: Missing to Grade 1 | Alanine Aminotransferase: Missing to Grade 2 | Alanine Aminotransferase: Missing to Missing | Aspartate Aminotransferase: Normal to Normal | Aspartate Aminotransferase: Normal to Grade 1 | Aspartate Aminotransferase: Normal to Grade 2 | Aspartate Aminotransferase: Normal to Grade 3 | Aspartate Aminotransferase: Normal to Missing | Aspartate Aminotransferase: Grade 1 to Normal | Aspartate Aminotransferase: Grade 1 to 1 | Aspartate Aminotransferase: Grade 1 to 2 | Aspartate Aminotransferase: Grade 1 to 3 | Aspartate Aminotransferase: Grade 1 to Missing | Aspartate Aminotransferase: Grade 2 to Normal | Aspartate Aminotransferase: Grade 2 to 1 | Aspartate Aminotransferase: Grade 2 to 2 | Aspartate Aminotransferase: Grade 2 to Missing | Aspartate Aminotransferase: Grade 3 to Normal | Aspartate Aminotransferase: Grade 3 to 1 | Aspartate Aminotransferase: Grade 3 to Missing | Aspartate Aminotransferase: Missing to Normal | Aspartate Aminotransferase: Missing to Grade 1 | Aspartate Aminotransferase: Missing to Grade 2 | Aspartate Aminotransferase: Missing to Missing | Albumin: Normal to Normal | Albumin: Normal to Grade 1 | Albumin: Normal to Grade 2 | Albumin: Normal to Grade 3 | Albumin: Normal to Missing | Albumin: Grade 1 to Normal | Albumin: Grade 1 to 1 | Albumin: Grade 1 to 2 | Albumin: Grade 1 to 3 | Albumin: Grade 1 to Missing | Albumin: Grade 2 to Normal | Albumin: Grade 2 to 1 | Albumin: Grade 2 to 2 | Albumin: Grade 2 to 3 | Albumin: Grade 2 to Missing | Albumin: Grade 3 to 2 | Albumin: Grade 3 to Missing | Albumin: Missing to Normal | Albumin: Missing to Grade 1 | Albumin: Missing to Grade 2 | Albumin: Missing to Missing | Alkaline Phosphatase: Normal to Normal | Alkaline Phosphatase: Normal to Grade 1 | Alkaline Phosphatase: Normal to Grade 2 | Alkaline Phosphatase: Normal to Grade 3 | Alkaline Phosphatase: Normal to Missing | Alkaline Phosphatase: Grade 1 to Normal | Alkaline Phosphatase: Grade 1 to 1 | Alkaline Phosphatase: Grade 1 to 2 | Alkaline Phosphatase: Grade 1 to 3 | Alkaline Phosphatase: Grade 1 to Missing | Alkaline Phosphatase: Grade 2 to Normal | Alkaline Phosphatase: Grade 2 to 1 | Alkaline Phosphatase: Grade 2 to 2 | Alkaline Phosphatase: Grade 2 to 3 | Alkaline Phosphatase: Grade 2 to Missing | Alkaline Phosphatase: Grade 3 to 1 | Alkaline Phosphatase: Grade 3 to 2 | Alkaline Phosphatase: Grade 3 to 3 | Alkaline Phosphatase: Missing to Normal | Alkaline Phosphatase: Missing to Grade 1 | Alkaline Phosphatase: Missing to Grade 3 | Alkaline Phosphatase: Missing to Missing | Calcium (High): Normal to Normal | Calcium (High): Normal to Grade 1 | Calcium (High): Normal to Grade 2 | Calcium (High): Normal to Grade 3 | Calcium (High): Normal to Grade 4 | Calcium (High): Normal to Missing | Calcium (High): Grade 1 to Normal | Calcium (High): Grade 1 to 1 | Calcium (High): Grade 1 to 2 | Calcium (High): Grade 1 to 3 | Calcium (High): Grade 1 to Missing | Calcium (High): Grade 2 to Normal | Calcium (High): Grade 2 to 1 | Calcium (High): Grade 2 to 2 | Calcium (High): Grade 3 to Normal | Calcium (High): Grade 3 to 1 | Calcium (High): Grade 3 to 2 | Calcium (High): Grade 4 to Normal | Calcium (High): Missing to Normal | Calcium (High): Missing to Grade 1 | Calcium (High): Missing to Missing | Calcium (Low): Normal to Normal | Calcium (Low): Normal to Grade 1 | Calcium (Low): Normal to Grade 2 | Calcium (Low): Normal to Grade 3 | Calcium (Low): Normal to Missing | Calcium (Low): Grade 1 to Normal | Calcium (Low): Grade 1 to 1 | Calcium (Low): Grade 1 to 2 | Calcium (Low): Grade 1 to 3 | Calcium (Low): Grade 1 to Missing | Calcium (Low): Grade 2 to Normal | Calcium (Low): Grade 2 to 1 | Calcium (Low): Grade 2 to 2 | Calcium (Low): Grade 3 to 3 | Calcium (Low): Missing to Normal | Calcium (Low): Missing to Grade 1 | Calcium (Low): Missing to Grade 2 | Calcium (Low): Missing to Missing | Creatinine: Normal to Normal | Creatinine: Normal to Grade 1 | Creatinine: Normal to Grade 2 | Creatinine: Normal to Grade 3 | Creatinine: Normal to Grade 4 | Creatinine: Normal to Missing | Creatinine: Grade 1 to Normal | Creatinine: Grade 1 to 1 | Creatinine: Grade 1 to 2 | Creatinine: Grade 1 to Missing | Creatinine: Grade 2 to 2 | Creatinine: Grade 2 to 3 | Creatinine: Grade 2 to Missing | Creatinine: Missing to Normal | Creatinine: Missing to Grade 1 | Creatinine: Missing to Missing | Gamma-Glutamyl Transpeptidase: Normal to Normal | Gamma-Glutamyl Transpeptidase: Normal to Grade 1 | Gamma-Glutamyl Transpeptidase: Normal to Grade 2 | Gamma-Glutamyl Transpeptidase: Normal to Grade 3 | Gamma-Glutamyl Transpeptidase: Normal to Missing | Gamma-Glutamyl Transpeptidase: Grade 1 to Normal | Gamma-Glutamyl Transpeptidase: Grade 1 to 1 | Gamma-Glutamyl Transpeptidase: Grade 1 to 2 | Gamma-Glutamyl Transpeptidase: Grade 1 to 3 | Gamma-Glutamyl Transpeptidase: Grade 1 to Missing | Gamma-Glutamyl Transpeptidase: Grade 2 to Normal | Gamma-Glutamyl Transpeptidase: Grade 2 to 1 | Gamma-Glutamyl Transpeptidase: Grade 2 to 2 | Gamma-Glutamyl Transpeptidase: Grade 2 to 3 | Gamma-Glutamyl Transpeptidase: Grade 2 to Missing | Gamma-Glutamyl Transpeptidase: Grade 3 to Normal | Gamma-Glutamyl Transpeptidase: Grade 3 to 1 | Gamma-Glutamyl Transpeptidase: Grade 3 to 2 | Gamma-Glutamyl Transpeptidase: Grade 3 to 3 | Gamma-Glutamyl Transpeptidase: Grade 3 to Missing | Gamma-Glutamyl Transpeptidase: Missing to Normal | Gamma-Glutamyl Transpeptidase: Missing to Grade 1 | Gamma-Glutamyl Transpeptidase: Missing to Grade 2 | Gamma-Glutamyl Transpeptidase: Missing to Grade 3 | Gamma-Glutamyl Transpeptidase: Missing to Missing | Glucose (High): Normal to Normal | Glucose (High): Normal to Grade 1 | Glucose (High): Normal to Grade 2 | Glucose (High): Normal to Missing | Glucose (High): Grade 1 to Normal | Glucose (High): Grade 1 to 1 | Glucose (High): Grade 1 to 2 | Glucose (High): Grade 1 to Missing | Glucose (High): Grade 2 to Normal | Glucose (High): Grade 2 to 1 | Glucose (High): Grade 2 to 2 | Glucose (High): Grade 2 to Missing | Glucose (High): Missing to Normal | Glucose (High): Missing to Grade 1 | Glucose (High): Missing to Grade 2 | Glucose (High): Missing to Missing | Glucose (Low): Normal to Normal | Glucose (Low): Normal to Grade 1 | Glucose (Low): Normal to Grade 2 | Glucose (Low): Normal to Grade 3 | Glucose (Low): Normal to Grade 4 | Glucose (Low): Normal to Missing | Glucose (Low): Grade 1 to Normal | Glucose (Low): Grade 1 to 1 | Glucose (Low): Grade 1 to 2 | Glucose (Low): Grade 1 to 3 | Glucose (Low): Grade 1 to 4 | Glucose (Low): Grade 2 to Normal | Glucose (Low): Missing to Normal | Glucose (Low): Missing to Grade 1 | Glucose (Low): Missing to Grade 2 | Glucose (Low): Missing to Grade 3 | Glucose (Low): Missing to Missing | Magnesium (High): Normal to Normal | Magnesium (High): Normal to Grade 1 | Magnesium (High): Normal to Grade 3 | Magnesium (High): Normal to Grade 4 | Magnesium (High): Normal to Missing | Magnesium (High): Grade 1 to Normal | Magnesium (High): Grade 1 to 1 | Magnesium (High): Grade 3 to Normal | Magnesium (High): Grade 3 to 3 | Magnesium (High): Grade 4 to Normal | Magnesium (High): Grade 4 to 4 | Magnesium (High): Missing to Normal | Magnesium (High): Missing to Grade 1 | Magnesium (High): Missing to Grade 3 | Magnesium (High): Missing to Missing | Magnesium (Low): Normal to Normal | Magnesium (Low): Normal to Grade 1 | Magnesium (Low): Normal to Grade 2 | Magnesium (Low): Normal to Grade 3 | Magnesium (Low): Normal to Grade 4 | Magnesium (Low): Normal to Missing | Magnesium (Low): Grade 1 to Normal | Magnesium (Low): Grade 1 to 1 | Magnesium (Low): Grade 1 to 2 | Magnesium (Low): Grade 1 to 3 | Magnesium (Low): Grade 1 to Missing | Magnesium (Low): Grade 4 to 4 | Magnesium (Low): Missing to Normal | Magnesium (Low): Missing to Grade 1 | Magnesium (Low): Missing to Grade 2 | Magnesium (Low): Missing to Grade 3 | Magnesium (Low): Missing to Grade 4 | Magnesium (Low): Missing to Missing | Potassium (High): Normal to Normal | Potassium (High): Normal to Grade 1 | Potassium (High): Normal to Grade 2 | Potassium (High): Normal to Grade 3 | Potassium (High): Normal to Grade 4 | Potassium (High): Normal to Missing | Potassium (High): Grade 1 to Normal | Potassium (High): Grade 1 to 1 | Potassium (High): Grade 1 to 2 | Potassium (High): Grade 1 to 3 | Potassium (High): Grade 1 to Missing | Potassium (High): Grade 2 to Normal | Potassium (High): Grade 2 to 1 | Potassium (High): Grade 2 to 2 | Potassium (High): Grade 4 to Normal | Potassium (High): Missing to Normal | Potassium (High): Missing to Grade 1 | Potassium (High): Missing to Grade 2 | Potassium (High): Missing to Missing | Potassium (Low): Normal to Normal | Potassium (Low): Normal to Grade 2 | Potassium (Low): Normal to Missing | Potassium (Low): Grade 2 to Normal | Potassium (Low): Grade 2 to 2 | Potassium (Low): Missing to Normal | Potassium (Low): Missing to Grade 2 | Potassium (Low): Missing to Missing | Sodium (High): Normal to Normal | Sodium (High): Normal to Grade 1 | Sodium (High): Normal to Grade 2 | Sodium (High): Normal to Grade 3 | Sodium (High): Normal to Grade 4 | Sodium (High): Normal to Missing | Sodium (High): Grade 1 to Normal | Sodium (High): Grade 1 to 1 | Sodium (High): Grade 1 to 2 | Sodium (High): Grade 1 to 3 | Sodium (High): Grade 2 to 2 | Sodium (High): Grade 2 to 3 | Sodium (High): Grade 3 to Normal | Sodium (High): Grade 3 to Missing | Sodium (High): Missing to Normal | Sodium (High): Missing to Grade 1 | Sodium (High): Missing to Missing | Sodium (Low): Normal to Normal | Sodium (Low): Normal to Grade 1 | Sodium (Low): Normal to Grade 3 | Sodium (Low): Normal to Grade 4 | Sodium (Low): Normal to Missing | Sodium (Low): Grade 1 to Normal | Sodium (Low): Grade 1 to 1 | Sodium (Low): Grade 1 to 3 | Sodium (Low): Grade 1 to 4 | Sodium (Low): Grade 1 to Missing | Sodium (Low): Grade 3 to Normal | Sodium (Low): Grade 3 to 1 | Sodium (Low): Grade 3 to 3 | Sodium (Low): Grade 4 to Normal | Sodium (Low): Grade 4 to 1 | Sodium (Low): Missing to Normal | Sodium (Low): Missing to Grade 1 | Sodium (Low): Missing to Grade 3 | Sodium (Low): Missing to Missing | Total Bilirubin: Normal to Normal | Total Bilirubin: Normal to Grade 1 | Total Bilirubin: Normal to Grade 2 | Total Bilirubin: Normal to Grade 3 | Total Bilirubin: Normal to Missing | Total Bilirubin: Grade 1 to Normal | Total Bilirubin: Grade 1 to 1 | Total Bilirubin: Grade 1 to 2 | Total Bilirubin: Grade 1 to Missing | Total Bilirubin: Grade 2 to 1 | Total Bilirubin: Grade 2 to 2 | Total Bilirubin: Grade 2 to Missing | Total Bilirubin: Grade 3 to Normal | Total Bilirubin: Missing to Normal | Total Bilirubin: Missing to Grade 2 | Total Bilirubin: Missing to Missing | Uric Acid: Normal to Normal | Uric Acid: Normal to Grade 1 | Uric Acid: Normal to Grade 4 | Uric Acid: Normal to Missing | Uric Acid: Grade 1 to Normal | Uric Acid: Grade 1 to 1 | Uric Acid: Grade 1 to 4 | Uric Acid: Grade 1 to Missing | Uric Acid: Grade 4 to Normal | Uric Acid: Grade 4 to 1 | Uric Acid: Grade 4 to 4 | Uric Acid: Grade 4 to Missing | Uric Acid: Missing to Normal | Uric Acid: Missing to Grade 1 | Uric Acid: Missing to Grade 4 | Uric Acid: Missing to Missing |
|---|
| Pertuzumab + Trastuzumab + Taxane | 610 | 425 | 26 | 19 | 25 | 75 | 151 | 26 | 14 | 6 | 8 | 28 | 5 | 1 | 2 | 7 | 4 | 1 | 3 | 562 | 386 | 22 | 9 | 15 | 120 | 187 | 24 | 9 | 14 | 13 | 29 | 3 | 3 | 2 | 7 | 1 | 13 | 9 | 2 | 6 | 785 | 357 | 86 | 10 | 23 | 13 | 43 | 35 | 1 | 7 | 3 | 5 | 8 | 2 | 2 | 1 | 1 | 28 | 14 | 6 | 6 | 605 | 329 | 14 | 2 | 18 | 44 | 241 | 72 | 15 | 6 | 2 | 21 | 24 | 14 | 8 | 2 | 1 | 4 | 7 | 3 | 1 | 3 | 1060 | 192 | 2 | 1 | 1 | 26 | 47 | 47 | 1 | 1 | 5 | 1 | 1 | 1 | 2 | 1 | 1 | 1 | 32 | 3 | 10 | 786 | 378 | 117 | 18 | 30 | 5 | 31 | 12 | 2 | 1 | 5 | 1 | 4 | 1 | 20 | 11 | 4 | 10 | 176 | 960 | 175 | 5 | 5 | 26 | 12 | 38 | 8 | 3 | 3 | 1 | 1 | 11 | 6 | 6 | 498 | 227 | 39 | 15 | 12 | 64 | 187 | 75 | 20 | 7 | 5 | 52 | 45 | 21 | 5 | 2 | 15 | 38 | 47 | 4 | 14 | 7 | 10 | 18 | 9 | 340 | 534 | 115 | 21 | 28 | 190 | 74 | 9 | 2 | 13 | 10 | 3 | 20 | 30 | 40 | 7 | 1061 | 173 | 19 | 4 | 5 | 33 | 8 | 24 | 3 | 1 | 1 | 1 | 69 | 16 | 2 | 1 | 15 | 1100 | 122 | 38 | 6 | 31 | 12 | 7 | 2 | 2 | 1 | 1 | 85 | 12 | 6 | 11 | 857 | 319 | 28 | 9 | 3 | 28 | 9 | 55 | 7 | 3 | 3 | 1 | 81 | 19 | 1 | 1 | 1 | 11 | 1051 | 183 | 81 | 18 | 8 | 26 | 16 | 8 | 7 | 1 | 3 | 2 | 1 | 1 | 1 | 18 | 5 | 3 | 3 | 990 | 367 | 29 | 8 | 13 | 19 | 7 | 3 | 1075 | 256 | 36 | 9 | 1 | 28 | 3 | 6 | 3 | 1 | 2 | 1 | 1 | 1 | 11 | 1 | 1 | 994 | 298 | 20 | 15 | 23 | 21 | 36 | 2 | 1 | 6 | 1 | 2 | 1 | 2 | 1 | 6 | 5 | 1 | 1 | 1231 | 88 | 35 | 2 | 28 | 3 | 11 | 6 | 2 | 1 | 1 | 1 | 1 | 22 | 1 | 3 | 933 | 190 | 8 | 20 | 58 | 120 | 6 | 11 | 1 | 2 | 4 | 1 | 57 | 13 | 2 | 10 |
Subgroup Analysis by Region of Enrollment: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Europe | 19.38 |
| Asia | 23.79 |
| North America | 25.17 |
| South America | 22.37 |
| Africa | 22.83 |
| Other (Australia) | NA |
Number of Participants With a Congestive Heart Failure Event
Congestive heart failure was defined as the Standardised MedDRA Query (SMQ) 'Cardiac failure (wide)' from the Medical Dictionary for Regulatory Activities, version 22.1 (MedDRA version 22.1). (NCT01572038)
Timeframe: From Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 478 |
Number of Participants With Grade ≥3 Treatment-Emergent Adverse Events, Occurring in ≥1% of Participants by System Organ Class and Preferred Term
Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs by system organ class (SOC) and preferred term (PT); PTs that are part of a given SOC are listed in the rows directly below each SOC within the results table. If a participant experienced the same AE at more than one severity grade, only the most severe grade was presented. (NCT01572038)
Timeframe: From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE - Grade (Gr.) 3 | Any TEAE - Gr. 4 | Any TEAE - Gr. 5 | Gastrointestinal Disorders (SOC) - Gr. 3 | Gastrointestinal Disorders (SOC) - Gr. 4 | Gastrointestinal Disorders (SOC) - Gr. 5 | Diarrhoea (PT) - Gr. 3 | Diarrhoea (PT) - Gr. 4 | Diarrhoea (PT) - Gr. 5 | Vomiting (PT) - Gr. 3 | Vomiting (PT) - Gr. 4 | Vomiting (PT) - Gr. 5 | Skin & Subcutaneous Tissue Disorders (SOC) - Gr. 3 | Skin & Subcutaneous Tissue Disorders (SOC) - Gr. 4 | Skin & Subcutaneous Tissue Disorders (SOC) - Gr. 5 | Gen. Disorders & Admin.Site Conditions (SOC)-Gr. 3 | Gen. Disorders & Admin.Site Conditions (SOC)-Gr. 4 | Gen. Disorders & Admin.Site Conditions (SOC)-Gr. 5 | Fatigue (PT) - Gr. 3 | Fatigue (PT) - Gr. 4 | Fatigue (PT) - Gr. 5 | Asthenia (PT) - Gr. 3 | Asthenia (PT) - Gr. 4 | Asthenia (PT) - Gr. 5 | Mucosal Inflammation (PT) - Gr. 3 | Mucosal Inflammation (PT) - Gr. 4 | Mucosal Inflammation (PT) - Gr. 5 | Nervous System Disorders (SOC) - Gr. 3 | Nervous System Disorders (SOC) - Gr. 4 | Nervous System Disorders (SOC) - Gr. 5 | Neuropathy Peripheral (PT) - Gr. 3 | Neuropathy Peripheral (PT) - Gr. 4 | Neuropathy Peripheral (PT) - Gr. 5 | Syncope (PT) - Gr. 3 | Syncope (PT) - Gr. 4 | Syncope (PT) - Gr. 5 | Headache (PT) - Gr. 3 | Headache (PT) - Gr. 4 | Headache (PT) - Gr. 5 | Paraesthesia (PT) - Gr. 3 | Paraesthesia (PT) - Gr. 4 | Paraesthesia (PT) - Gr. 5 | Peripheral Sensory Neuropathy (PT) - Gr. 3 | Peripheral Sensory Neuropathy (PT) - Gr. 4 | Peripheral Sensory Neuropathy (PT) - Gr. 5 | Infections and Infestations (SOC) - Gr. 3 | Infections and Infestations (SOC) - Gr. 4 | Infections and Infestations (SOC) - Gr. 5 | Pneumonia (PT) - Gr. 3 | Pneumonia (PT) - Gr. 4 | Pneumonia (PT) - Gr. 5 | Vascular Device Infection (PT) - Gr. 3 | Vascular Device Infection (PT) - Gr. 4 | Vascular Device Infection (PT) - Gr. 5 | Device Related Infection (PT) - Gr. 3 | Device Related Infection (PT) - Gr. 4 | Device Related Infection (PT) - Gr. 5 | Musculo. & Connective Tissue Disorders (SOC)-Gr. 3 | Musculo. & Connective Tissue Disorders (SOC)-Gr. 4 | Musculo. & Connective Tissue Disorders (SOC)-Gr. 5 | Resp., Thoracic & Mediast. Disorders (SOC) - Gr. 3 | Resp., Thoracic & Mediast. Disorders (SOC) - Gr. 4 | Resp., Thoracic & Mediast. Disorders (SOC) - Gr. 5 | Pulmonary Embolism (PT) - Gr. 3 | Pulmonary Embolism (PT) - Gr. 4 | Pulmonary Embolism (PT) - Gr. 5 | Dyspnoea (PT) - Gr. 3 | Dyspnoea (PT) - Gr. 4 | Dyspnoea (PT) - Gr. 5 | Blood & Lymphatic System Disorders (SOC) - Gr. 3 | Blood & Lymphatic System Disorders (SOC) - Gr. 4 | Blood & Lymphatic System Disorders (SOC) - Gr. 5 | Neutropenia (PT) - Gr. 3 | Neutropenia (PT) - Gr. 4 | Neutropenia (PT) - Gr. 5 | Febrile Neutropenia (PT) - Gr. 3 | Febrile Neutropenia (PT) - Gr. 4 | Febrile Neutropenia (PT) - Gr. 5 | Anaemia (PT) - Gr. 3 | Anaemia (PT) - Gr. 4 | Anaemia (PT) - Gr. 5 | Leukopenia (PT) - Gr. 3 | Leukopenia (PT) - Gr. 4 | Leukopenia (PT) - Gr. 5 | Investigations (SOC) - Gr. 3 | Investigations (SOC) - Gr. 4 | Investigations (SOC) - Gr. 5 | Neutrophil Count Decreased (PT) - Gr. 3 | Neutrophil Count Decreased (PT) - Gr. 4 | Neutrophil Count Decreased (PT) - Gr. 5 | Ejection Fraction Decreased (PT) - Gr. 3 | Ejection Fraction Decreased (PT) - Gr. 4 | Ejection Fraction Decreased (PT) - Gr. 5 | Gamma-Glutamyltransferase Increased (PT) - Gr. 3 | Gamma-Glutamyltransferase Increased (PT) - Gr. 4 | Gamma-Glutamyltransferase Increased (PT) - Gr. 5 | White Blood Cell Count Decreased (PT) - Gr. 3 | White Blood Cell Count Decreased (PT) - Gr. 4 | White Blood Cell Count Decreased (PT) - Gr. 5 | Alanine Aminotransferase Increased (PT) - Gr. 3 | Alanine Aminotransferase Increased (PT) - Gr. 4 | Alanine Aminotransferase Increased (PT) - Gr. 5 | Metabolism and Nutrition Disorders (SOC) - Gr. 3 | Metabolism and Nutrition Disorders (SOC) - Gr. 4 | Metabolism and Nutrition Disorders (SOC) - Gr. 5 | Hypokalaemia (PT) - Gr. 3 | Hypokalaemia (PT) - Gr. 4 | Hypokalaemia (PT) - Gr. 5 | Vascular Disorders (SOC) - Gr. 3 | Vascular Disorders (SOC) - Gr. 4 | Vascular Disorders (SOC) - Gr. 5 | Hypertension (PT) - Gr. 3 | Hypertension (PT) - Gr. 4 | Hypertension (PT) - Gr. 5 | Psychiatric Disorders (SOC) - Gr. 3 | Psychiatric Disorders (SOC) - Gr. 4 | Psychiatric Disorders (SOC) - Gr. 5 | Injury, Poisoning & Proced. Complicat. (SOC)-Gr. 3 | Injury, Poisoning & Proced. Complicat. (SOC)-Gr. 4 | Injury, Poisoning & Proced. Complicat. (SOC)-Gr. 5 | Cardiac Disorders (SOC) - Gr. 3 | Cardiac Disorders (SOC) - Gr. 4 | Cardiac Disorders (SOC) - Gr. 5 | Immune System Disorders (SOC) - Gr. 3 | Immune System Disorders (SOC) - Gr. 4 | Immune System Disorders (SOC) - Gr. 5 | Renal and Urinary Disorders (SOC) - Gr. 3 | Renal and Urinary Disorders (SOC) - Gr. 4 | Renal and Urinary Disorders (SOC) - Gr. 5 | Neoplasms Benign, Malignant & Unspec. (SOC) -Gr. 3 | Neoplasms Benign, Malignant & Unspec. (SOC) -Gr. 4 | Neoplasms Benign, Malignant & Unspec. (SOC) -Gr. 5 | Hepatobiliary Disorders (SOC) - Gr. 3 | Hepatobiliary Disorders (SOC) - Gr. 4 | Hepatobiliary Disorders (SOC) - Gr. 5 |
|---|
| Pertuzumab + Trastuzumab + Taxane | 676 | 172 | 31 | 163 | 4 | 2 | 119 | 1 | 0 | 19 | 0 | 0 | 56 | 0 | 0 | 100 | 0 | 3 | 36 | 0 | 0 | 29 | 0 | 0 | 14 | 0 | 0 | 139 | 0 | 2 | 26 | 0 | 0 | 24 | 0 | 0 | 17 | 0 | 0 | 14 | 0 | 0 | 14 | 0 | 0 | 148 | 19 | 10 | 22 | 1 | 4 | 14 | 0 | 0 | 14 | 0 | 0 | 75 | 0 | 0 | 62 | 5 | 3 | 21 | 2 | 0 | 19 | 1 | 0 | 158 | 104 | 3 | 77 | 67 | 1 | 51 | 38 | 1 | 29 | 0 | 0 | 15 | 3 | 0 | 116 | 20 | 0 | 25 | 13 | 0 | 22 | 2 | 0 | 19 | 1 | 0 | 16 | 2 | 0 | 16 | 0 | 0 | 63 | 8 | 1 | 19 | 1 | 0 | 62 | 2 | 0 | 45 | 1 | 0 | 15 | 3 | 1 | 43 | 6 | 0 | 35 | 5 | 7 | 17 | 1 | 0 | 15 | 3 | 0 | 13 | 5 | 0 | 13 | 0 | 1 |
Number of Participants by Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Categories Over the Course of the Study
All participants must have had a baseline LVEF greater than or equal to (≥)50% to enroll in the study; patients with significant cardiac disease or baseline LVEF below 50% were not eligible for this study. The number of participants are reported according to four change from baseline in LVEF value categories over the course of the study: 1) an increase or decrease from baseline LVEF less than (<)10% points or no change in LVEF; 2) an absolute LVEF value <45% points and a decrease from baseline LVEF ≥10% points to <15% points; 3) an absolute LVEF value <45% points and a decrease from baseline LVEF ≥15% points; or 4) an absolute LVEF value ≥45% points and a decrease from baseline LVEF ≥10% points. BL = baseline; Decr. = decrease; Incr. = increase (NCT01572038)
Timeframe: Baseline, predose on Day 1 of every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 372053586 | Cycle 672053586 | Cycle 972053586 | Cycle 1272053586 | Cycle 1572053586 | Cycle 1872053586 | Cycle 2172053586 | Cycle 2472053586 | Cycle 2772053586 | Cycle 3072053586 | Cycle 3372053586 | Cycle 3672053586 | Cycle 3972053586 | Cycle 4272053586 | Cycle 4572053586 | Cycle 4872053586 | Cycle 5172053586 | Cycle 5472053586 | Cycle 5772053586 | Cycle 6072053586 | Cycle 6372053586 | Cycle 6672053586 | Cycle 6972053586 | Cycle 7272053586 | Cycle 7572053586 | Cycle 7872053586 | Cycle 8172053586 | Cycle 8472053586 | Cycle 8772053586 | Cycle 9072053586 | Cycle 9372053586 | Cycle 9672053586 | Cycle 9972053586 | Cycle 10272053586 | Cycle 10572053586 | Cycle 10872053586 | Cycle 11172053586 | Cycle 11472053586 | Cycle 11772053586 | Cycle 12072053586 | Cycle 12372053586 | Cycle 12672053586 | End of Treatment72053586 | Day 28 of Follow-Up72053586 |
|---|
| LVEF≥45% Points and Decr. from BL ≥10% Points | Incr. or Decr. from BL <10% Points, or No Change | LVEF<45% Points and Decr. from BL ≥10%-<15% Points | LVEF<45% Points and Decr. from BL ≥15% Points |
|---|
| Pertuzumab + Trastuzumab + Taxane | 1190 |
| Pertuzumab + Trastuzumab + Taxane | 114 |
| Pertuzumab + Trastuzumab + Taxane | 1110 |
| Pertuzumab + Trastuzumab + Taxane | 136 |
| Pertuzumab + Trastuzumab + Taxane | 1005 |
| Pertuzumab + Trastuzumab + Taxane | 4 |
| Pertuzumab + Trastuzumab + Taxane | 139 |
| Pertuzumab + Trastuzumab + Taxane | 906 |
| Pertuzumab + Trastuzumab + Taxane | 116 |
| Pertuzumab + Trastuzumab + Taxane | 780 |
| Pertuzumab + Trastuzumab + Taxane | 109 |
| Pertuzumab + Trastuzumab + Taxane | 719 |
| Pertuzumab + Trastuzumab + Taxane | 5 |
| Pertuzumab + Trastuzumab + Taxane | 639 |
| Pertuzumab + Trastuzumab + Taxane | 88 |
| Pertuzumab + Trastuzumab + Taxane | 588 |
| Pertuzumab + Trastuzumab + Taxane | 91 |
| Pertuzumab + Trastuzumab + Taxane | 553 |
| Pertuzumab + Trastuzumab + Taxane | 78 |
| Pertuzumab + Trastuzumab + Taxane | 518 |
| Pertuzumab + Trastuzumab + Taxane | 70 |
| Pertuzumab + Trastuzumab + Taxane | 485 |
| Pertuzumab + Trastuzumab + Taxane | 72 |
| Pertuzumab + Trastuzumab + Taxane | 446 |
| Pertuzumab + Trastuzumab + Taxane | 62 |
| Pertuzumab + Trastuzumab + Taxane | 414 |
| Pertuzumab + Trastuzumab + Taxane | 65 |
| Pertuzumab + Trastuzumab + Taxane | 405 |
| Pertuzumab + Trastuzumab + Taxane | 46 |
| Pertuzumab + Trastuzumab + Taxane | 358 |
| Pertuzumab + Trastuzumab + Taxane | 69 |
| Pertuzumab + Trastuzumab + Taxane | 340 |
| Pertuzumab + Trastuzumab + Taxane | 49 |
| Pertuzumab + Trastuzumab + Taxane | 314 |
| Pertuzumab + Trastuzumab + Taxane | 43 |
| Pertuzumab + Trastuzumab + Taxane | 292 |
| Pertuzumab + Trastuzumab + Taxane | 291 |
| Pertuzumab + Trastuzumab + Taxane | 284 |
| Pertuzumab + Trastuzumab + Taxane | 263 |
| Pertuzumab + Trastuzumab + Taxane | 39 |
| Pertuzumab + Trastuzumab + Taxane | 249 |
| Pertuzumab + Trastuzumab + Taxane | 35 |
| Pertuzumab + Trastuzumab + Taxane | 237 |
| Pertuzumab + Trastuzumab + Taxane | 0 |
| Pertuzumab + Trastuzumab + Taxane | 33 |
| Pertuzumab + Trastuzumab + Taxane | 224 |
| Pertuzumab + Trastuzumab + Taxane | 1 |
| Pertuzumab + Trastuzumab + Taxane | 29 |
| Pertuzumab + Trastuzumab + Taxane | 214 |
| Pertuzumab + Trastuzumab + Taxane | 2 |
| Pertuzumab + Trastuzumab + Taxane | 196 |
| Pertuzumab + Trastuzumab + Taxane | 30 |
| Pertuzumab + Trastuzumab + Taxane | 192 |
| Pertuzumab + Trastuzumab + Taxane | 23 |
| Pertuzumab + Trastuzumab + Taxane | 174 |
| Pertuzumab + Trastuzumab + Taxane | 22 |
| Pertuzumab + Trastuzumab + Taxane | 161 |
| Pertuzumab + Trastuzumab + Taxane | 16 |
| Pertuzumab + Trastuzumab + Taxane | 140 |
| Pertuzumab + Trastuzumab + Taxane | 115 |
| Pertuzumab + Trastuzumab + Taxane | 13 |
| Pertuzumab + Trastuzumab + Taxane | 92 |
| Pertuzumab + Trastuzumab + Taxane | 14 |
| Pertuzumab + Trastuzumab + Taxane | 68 |
| Pertuzumab + Trastuzumab + Taxane | 56 |
| Pertuzumab + Trastuzumab + Taxane | 9 |
| Pertuzumab + Trastuzumab + Taxane | 41 |
| Pertuzumab + Trastuzumab + Taxane | 34 |
| Pertuzumab + Trastuzumab + Taxane | 8 |
| Pertuzumab + Trastuzumab + Taxane | 19 |
| Pertuzumab + Trastuzumab + Taxane | 11 |
| Pertuzumab + Trastuzumab + Taxane | 6 |
| Pertuzumab + Trastuzumab + Taxane | 3 |
| Pertuzumab + Trastuzumab + Taxane | 431 |
| Pertuzumab + Trastuzumab + Taxane | 26 |
| Pertuzumab + Trastuzumab + Taxane | 87 |
| Pertuzumab + Trastuzumab + Taxane | 472 |
| Pertuzumab + Trastuzumab + Taxane | 86 |
Percentage of Participants by Best Overall Response as Assessed by the Investigator Using RECIST v1.1
Best overall response (BOR) was defined as the best response recorded from the first dose of study treatment until disease progression/recurrence or death in the absence of disease progression. The hierarchy used to determine BOR: Complete Response (CR)>Partial Response (PR)>Stable Disease (SD)>Progressive Disease (PD)>Not Evaluable. Note that CR or PR was confirmed ≥4 weeks later. RECIST v1.1 responses are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum.; PD = At least 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study, and absolute increase of ≥5 mm.; 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. (NCT01572038)
Timeframe: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Percentage of participants (Number) |
|---|
| Complete Response (Confirmed) | Partial Response (Confirmed) | Stable Disease | Progressive Disease | Not Evaluable |
|---|
| Pertuzumab + Trastuzumab + Taxane | 14.6 | 64.9 | 15.3 | 4.2 | 1.1 |
Overview of the Number of Participants With at Least One Treatment-Emergent Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0)
Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent. TEAEs of special interest included LVEF decreased, liver enzymes increased, and suspected transmission of infectious agent by the study drug. (NCT01572038)
Timeframe: From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE - Any Grade | Any TEAE - Grade 3 or Higher (≥3) | Any Serious TEAE | Any TEAE Leading to Death | Any TEAE Related to Pertuzumab - Any Grade | Any TEAE Related to Trastuzumab - Any Grade | Any TEAE Related to Taxane - Any Grade | Any TEAE Related to Pertuzumab - Grade ≥3 | Any TEAE Related to Trastuzumab - Grade ≥3 | Any TEAE Related to Taxane - Grade ≥3 | Any TEAE Leading to Interruption of Pertuzumab | Any TEAE Leading to Interruption of Trastuzumab | Any TEAE Leading to Interruption of Taxane | Any TEAE Leading to Discontinuation of Pertuzumab | Any TEAE Leading to Discontinuation of Trastuzumab | Any TEAE Leading to Discontinuation of Taxane | Any TEAE to Monitor - Any Grade | Any TEAE to Monitor - Grade ≥3 | Any TEAE of Special Interest | Any TEAE Within 28 Days of Treatmt Discontinuation |
|---|
| Pertuzumab + Trastuzumab + Taxane | 1419 | 879 | 535 | 31 | 1037 | 946 | 1342 | 286 | 245 | 514 | 334 | 386 | 354 | 140 | 133 | 286 | 1320 | 535 | 91 | 975 |
Change From Baseline in FACT-B Questionnaire Emotional Well-Being Subscale Score Over the Course of the Study
The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the emotional well-being subscale, participants were given a series of 6 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B emotional well-being subscale score, ranging from 0 to 24, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only. (NCT01572038)
Timeframe: Baseline, every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Score on a scale (Mean) |
|---|
| Baseline (BL): Absolute Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Cycle 54 | Change from BL at Cycle 57 | Change from BL at Cycle 60 | Change from BL at Cycle 63 | Change from BL at Cycle 66 | Change from BL at Cycle 69 | Change from BL at Cycle 72 | Change from BL at Cycle 75 | Change from BL at Cycle 78 | Change from BL at Cycle 81 | Change from BL at Cycle 84 | Change from BL at Cycle 87 | Change from BL at Cycle 90 | Change from BL at Cycle 93 | Change from BL at Cycle 96 | Change from BL at Cycle 99 | Change from BL at Cycle 102 | Change from BL at Cycle 105 | Change from BL at Cycle 108 | Change from BL at Cycle 111 | Change from BL at Cycle 114 | Change from BL at Cycle 117 | Change from BL at Cycle 120 | Change from BL at Cycle 123 | Change from BL at End of Treatment | Change from BL at Day 28 of Follow-Up |
|---|
| Pertuzumab + Trastuzumab + Taxane | 15.08 | 1.69 | 1.53 | 1.64 | 2.02 | 1.98 | 2.03 | 2.17 | 2.19 | 2.21 | 2.17 | 2.21 | 2.32 | 1.99 | 1.96 | 2.25 | 1.82 | 2.32 | 1.84 | 1.80 | 1.59 | 1.70 | 1.52 | 1.83 | 1.56 | 1.58 | 1.72 | 2.01 | 2.06 | 1.97 | 2.08 | 2.17 | 2.40 | 2.30 | 2.07 | 2.58 | 2.34 | 1.19 | 1.55 | 1.33 | 0.75 | -0.50 | 0.30 | 0.37 |
Change From Baseline in FACT-B Questionnaire Functional Well-Being Subscale Score Over the Course of the Study
The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the functional well-being subscale, participants were given a series of 7 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B functional well-being subscale score, ranging from 0 to 28, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only. (NCT01572038)
Timeframe: Baseline, every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Score on a scale (Mean) |
|---|
| Baseline (BL): Absolute Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Cycle 54 | Change from BL at Cycle 57 | Change from BL at Cycle 60 | Change from BL at Cycle 63 | Change from BL at Cycle 66 | Change from BL at Cycle 69 | Change from BL at Cycle 72 | Change from BL at Cycle 75 | Change from BL at Cycle 78 | Change from BL at Cycle 81 | Change from BL at Cycle 84 | Change from BL at Cycle 87 | Change from BL at Cycle 90 | Change from BL at Cycle 93 | Change from BL at Cycle 96 | Change from BL at Cycle 99 | Change from BL at Cycle 102 | Change from BL at Cycle 105 | Change from BL at Cycle 108 | Change from BL at Cycle 111 | Change from BL at Cycle 114 | Change from BL at Cycle 117 | Change from BL at Cycle 120 | Change from BL at Cycle 123 | Change from BL at End of Treatment | Change from BL at Day 28 of Follow-Up |
|---|
| Pertuzumab + Trastuzumab + Taxane | 16.65 | -0.47 | -0.79 | -0.11 | 0.46 | 0.78 | 0.83 | 0.89 | 0.53 | 0.71 | 0.60 | 0.67 | 0.52 | 0.26 | 0.31 | 0.34 | 0.28 | 0.23 | -0.06 | 0.21 | 0.01 | -0.06 | -0.07 | -0.47 | -0.50 | -0.40 | -0.18 | -0.29 | -0.48 | -0.08 | 0.16 | 0.58 | 1.27 | 0.46 | 0.96 | 1.14 | 1.42 | 0.32 | -0.25 | -0.58 | -2.00 | -5.00 | -0.50 | -0.70 |
Change From Baseline in FACT-B Questionnaire Physical Well-Being Subscale Score Over the Course of the Study
The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the physical well-being subscale, participants were given a series of 7 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B physical well-being subscale score, ranging from 0 to 28, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only. (NCT01572038)
Timeframe: Baseline, every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Score on a scale (Mean) |
|---|
| Baseline (BL): Absolute Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Cycle 54 | Change from BL at Cycle 57 | Change from BL at Cycle 60 | Change from BL at Cycle 63 | Change from BL at Cycle 66 | Change from BL at Cycle 69 | Change from BL at Cycle 72 | Change from BL at Cycle 75 | Change from BL at Cycle 78 | Change from BL at Cycle 81 | Change from BL at Cycle 84 | Change from BL at Cycle 87 | Change from BL at Cycle 90 | Change from BL at Cycle 93 | Change from BL at Cycle 96 | Change from BL at Cycle 99 | Change from BL at Cycle 102 | Change from BL at Cycle 105 | Change from BL at Cycle 108 | Change from BL at Cycle 111 | Change from BL at Cycle 114 | Change from BL at Cycle 117 | Change from BL at Cycle 120 | Change from BL at Cycle 123 | Change from BL at End of Treatment | Change from BL at Day 28 of Follow-Up |
|---|
| Pertuzumab + Trastuzumab + Taxane | 20.98 | -1.13 | -1.61 | -0.31 | 0.51 | 0.51 | 0.69 | 0.73 | 0.61 | 0.47 | 0.71 | 0.56 | 0.39 | -0.04 | 0.22 | 0.09 | 0.11 | 0.22 | -0.26 | -0.35 | -0.10 | -0.20 | 0.29 | -0.60 | -0.35 | -0.72 | -0.44 | -0.65 | -0.81 | -0.36 | -0.66 | -0.42 | -0.28 | -0.21 | -0.80 | -0.07 | 0.07 | 0.38 | -1.70 | -1.83 | -2.38 | -5.58 | -0.73 | -0.95 |
Change From Baseline in FACT-B Questionnaire Social Well-Being Subscale Score Over the Course of the Study
The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. For the social well-being subscale, participants were given a series of 7 statements and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B social well-being subscale score, ranging from 0 to 28, was the sum of the scores for each statement only if at least 50% of items had been answered; the higher the score, the better the quality of life. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only. (NCT01572038)
Timeframe: Baseline, every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Score on a scale (Mean) |
|---|
| Baseline (BL): Absolute Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Cycle 54 | Change from BL at Cycle 57 | Change from BL at Cycle 60 | Change from BL at Cycle 63 | Change from BL at Cycle 66 | Change from BL at Cycle 69 | Change from BL at Cycle 72 | Change from BL at Cycle 75 | Change from BL at Cycle 78 | Change from BL at Cycle 81 | Change from BL at Cycle 84 | Change from BL at Cycle 87 | Change from BL at Cycle 90 | Change from BL at Cycle 93 | Change from BL at Cycle 96 | Change from BL at Cycle 99 | Change from BL at Cycle 102 | Change from BL at Cycle 105 | Change from BL at Cycle 108 | Change from BL at Cycle 111 | Change from BL at Cycle 114 | Change from BL at Cycle 117 | Change from BL at Cycle 120 | Change from BL at Cycle 123 | Change from BL at End of Treatment | Change from BL at Day 28 of Follow-Up |
|---|
| Pertuzumab + Trastuzumab + Taxane | 22.24 | -0.41 | -1.09 | -1.02 | -1.19 | -1.28 | -1.19 | -1.24 | -1.26 | -1.48 | -1.18 | -1.45 | -1.54 | -1.77 | -1.73 | -1.50 | -1.84 | -2.01 | -1.77 | -1.88 | -2.01 | -2.18 | -2.19 | -2.24 | -2.49 | -2.40 | -2.33 | -2.53 | -2.96 | -2.29 | -2.38 | -1.97 | -1.94 | -2.07 | -1.70 | -1.76 | -1.75 | -1.94 | -2.31 | -1.83 | -2.85 | -1.92 | -1.29 | -1.61 |
Number of Participants With Treatment-Emergent Adverse Events to Monitor of Any Grade, Occurring in ≥5% of Participants by Category
Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first dose of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, it was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. If a participant had more than one event in a category, they were counted only once in that category. TEAEs to monitor included anaphylaxis and hypersensitivity, cardiac dysfunction, diarrhoea Grade ≥3, pregnancy-related AEs, interstitial lung disease, infusion-/administration-related reactions, mucositis, (febrile) neutropenia, rash/skin reactions, and suspected transmission of infectious agent. MedDRA version 22.1 was used to code AEs; AEs may fall within multiple categories. (NCT01572038)
Timeframe: From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE to Monitor | Infusion-/Administration-Related Reactions | Rash/Skin Reactions | Mucositis | Cardiac Dysfunction | Neutropenia/Febrile Neutropenia | Anaphylaxis and Hypersensitivity | Diarrhoea Grade ≥3 |
|---|
| Pertuzumab + Trastuzumab + Taxane | 1320 | 1096 | 668 | 618 | 478 | 439 | 124 | 120 |
Change From Baseline in Functional Assessment of Cancer Therapy - Breast Cancer (FACT-B) Questionnaire Total Score Over the Course of the Study
The FACT-B questionnaire (version 4) was administered only to female participants to assess quality of life in five subscales: physical, social, emotional, and functional well-being, and breast cancer. Participants were given a series of statements in each subscale and were asked to rate how true each statement was for them during the past 7 days on a 5-point scale ranging from 0 (not at all) to 4 (very much). The calculated FACT-B total score, ranging from 0 to 148, was the sum of the scores for each subscale, provided that at least 80% of the items had been answered; a higher score indicated a better quality of life. If any of the 5 subscale scores were missing, the total score was also set to missing. Baseline was defined as the last non-missing measurement taken prior to first dose of study treatment (including unscheduled assessments). Post-baseline values were summarized for planned visits only. (NCT01572038)
Timeframe: Baseline, every 3 cycles (1 cycle is 3 weeks) during treatment period, and 28 days post-treatment safety follow-up. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Score on a scale (Mean) |
|---|
| Baseline (BL): Absolute Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Cycle 54 | Change from BL at Cycle 57 | Change from BL at Cycle 60 | Change from BL at Cycle 63 | Change from BL at Cycle 66 | Change from BL at Cycle 69 | Change from BL at Cycle 72 | Change from BL at Cycle 75 | Change from BL at Cycle 78 | Change from BL at Cycle 81 | Change from BL at Cycle 84 | Change from BL at Cycle 87 | Change from BL at Cycle 90 | Change from BL at Cycle 93 | Change from BL at Cycle 96 | Change from BL at Cycle 99 | Change from BL at Cycle 102 | Change from BL at Cycle 105 | Change from BL at Cycle 108 | Change from BL at Cycle 111 | Change from BL at Cycle 114 | Change from BL at Cycle 117 | Change from BL at Cycle 120 | Change from BL at Cycle 123 | Change from BL at End of Treatment | Change from BL at Day 28 of Follow-Up |
|---|
| Pertuzumab + Trastuzumab + Taxane | 99.87 | 0.40 | -1.93 | 0.87 | 3.03 | 3.33 | 3.80 | 4.06 | 3.59 | 3.14 | 3.75 | 3.58 | 3.16 | 1.66 | 2.08 | 2.22 | 1.51 | 1.95 | 0.52 | 0.54 | 0.20 | 0.61 | 0.44 | -0.75 | -1.16 | -1.14 | 0.11 | -1.03 | -1.67 | 0.62 | 0.00 | 0.99 | 2.36 | 1.36 | 1.20 | 3.13 | 2.22 | -0.48 | -4.42 | -4.96 | -8.64 | -20.94 | -1.06 | -1.96 |
Clinical Benefit Rate (CR or PR, or SD for at Least 6 Months) Based on Best Overall Response as Assessed by the Investigator Using RECIST v.1.1
The clinical benefit rate was defined as the percentage of participants whose best confirmed response (≥4 weeks later) was a complete response (CR) or partial response (PR), or stable disease (SD) that lasted at least 6 months, as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Clinical benefit responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (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 progressive disease (PD; at least 20% increase in sum of diameters of target lesions and absolute increase of ≥5 mm), taking as reference the smallest sum diameters while on study. (NCT01572038)
Timeframe: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 86.2 |
Duration of Response as Assessed by the Investigator Using RECIST v1.1
Duration of response (DOR) was defined as the time from when a confirmed best overall response of complete response (CR) or partial response (PR) was first documented to first documented disease progression or death from any cause (whichever occurred first). DOR was analyzed using a Kaplan-Meier approach. Participants who had not progressed or died after having had a confirmed response were censored at the date of their last tumor measurement. Response was assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter until event occurrence or end of study. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT01572038)
Timeframe: From date of first confirmed response (CR or PR) to first documented disease progression or death from any cause, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 20.01 |
Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1
The overall response rate was defined as the percentage of participants with complete response (CR) or partial response (PR) as their best confirmed response (≥4 weeks later), as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants without post-baseline tumor assessments were considered non-responders. (NCT01572038)
Timeframe: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Percentage of participants (Number) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 79.5 |
Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 65.31 |
Progression-Free Survival, as Assessed by the Investigator Using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 20.67 |
Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1
The overall response rate was defined as the percentage of participants with complete response (CR) or partial response (PR) as their best confirmed response (≥4 weeks later), as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants without post-baseline tumor assessments were considered non-responders. (NCT01572038)
Timeframe: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Percentage of participants (Number) |
|---|
| Age ≤65 Years | 81.7 |
| Age >65 Years | 70.0 |
Subgroup Analysis by Age (≤65 vs. >65 Years): Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Age ≤65 Years | 70.01 |
| Age >65 Years | 50.10 |
Subgroup Analysis by Age (≤65 vs. >65 Years): Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Age ≤65 Years | 21.98 |
| Age >65 Years | 14.72 |
Subgroup Analysis by Hormone Receptor Status at Baseline: Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Hormone Receptor Positive | 66.66 |
| Hormone Receptor Negative | 60.19 |
| Hormone Receptor Status Unknown | NA |
Subgroup Analysis by Hormone Receptor Status at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Hormone Receptor Positive | 20.60 |
| Hormone Receptor Negative | 20.73 |
| Hormone Receptor Status Unknown | 32.13 |
Subgroup Analysis by Previous Trastuzumab Therapy: Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Previous Trastuzumab Therapy | 54.08 |
| No Previous Trastuzumab Therapy | 73.50 |
Subgroup Analysis by Previous Trastuzumab Therapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Previous Trastuzumab Therapy | 15.38 |
| No Previous Trastuzumab Therapy | 23.39 |
Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Prior (Neo)Adjuvant Chemotherapy | 57.10 |
| No Prior (Neo)Adjuvant Chemotherapy | 79.80 |
Subgroup Analysis by Prior (Neo)Adjuvant Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Prior (Neo)Adjuvant Chemotherapy | 19.12 |
| No Prior (Neo)Adjuvant Chemotherapy | 23.49 |
Subgroup Analysis by Region of Enrollment: Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Europe | 66.56 |
| Asia | 63.57 |
| North America | 55.56 |
| South America | NA |
| Africa | 53.22 |
| Other (Australia) | NA |
Subgroup Analysis by Taxane Chemotherapy: Overall Response Rate (Complete Response or Partial Response) Based on Best Overall Response (Confirmed) as Assessed by the Investigator Using RECIST v1.1
The overall response rate was defined as the percentage of participants with complete response (CR) or partial response (PR) as their best confirmed response (≥4 weeks later), as assessed by the investigator using RECIST v1.1 from the start of study treatment until disease progression/recurrence or death. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Participants without post-baseline tumor assessments were considered non-responders. (NCT01572038)
Timeframe: Assessed every 3 cycles (1 cycle is 3 weeks) up to 36 months, and at least every 12 cycles thereafter, until disease progression or death. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Percentage of participants (Number) |
|---|
| Docetaxel | 78.4 |
| Paclitaxel | 82.1 |
| Nab-Paclitaxel | 77.4 |
Subgroup Analysis by Taxane Chemotherapy: Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Docetaxel | 66.53 |
| Paclitaxel | 64.03 |
| Nab-Paclitaxel | 70.87 |
Subgroup Analysis by Taxane Chemotherapy: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Docetaxel | 19.38 |
| Paclitaxel | 23.23 |
| Nab-Paclitaxel | 19.22 |
Subgroup Analysis by Visceral Disease at Baseline: Overall Survival
Overall survival was defined as time from the date of enrollment until the date of death due to any cause. Overall survival was analyzed using a Kaplan-Meier approach. Participants who had not died were censored at the last date they were known to be alive. When it was not possible to confirm the full death date, partial death dates were imputed to: 01 June of that year if only the year was known, 15th of that month if only the month and year were known. If the imputed date was before the last known alive date, the last known alive date was used as the imputation. (NCT01572038)
Timeframe: From date of enrollment until death due to any cause. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Visceral Disease | 57.10 |
| Non-Visceral Disease | 81.08 |
Subgroup Analysis by Visceral Disease at Baseline: Progression-Free Survival, as Assessed by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time between the date of enrollment and the date of first radiographically documented progressive disease assessment (by the investigator using RECIST v1.1) or death, whichever occurred first. PFS was analyzed using a Kaplan-Meier approach. Participants who had neither progressed nor died at the time of clinical cut-off or who were lost to follow-up were censored at the date of the last evaluable tumor assessment (response assessment with the latest end date); if no post-baseline assessments were available, such participants were censored at Day 1. If a participant missed 2 or more consecutive visits, then they were censored at the last evaluable visit prior to the missed visits. Tumor assessments were performed every 3 cycles (1 cycle is 3 weeks) for up to 36 months and at least every 12 cycles thereafter during treatment, and at least every 36 weeks post-treatment (if progression-free after 36 months), until disease progression. (NCT01572038)
Timeframe: From date of enrollment until date of disease progression or death, whichever occurred first. The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Visceral Disease | 18.23 |
| Non-Visceral Disease | 27.24 |
Time to Onset of the First Episode of Congestive Heart Failure
Congestive heart failure was defined as SMQ 'Cardiac failure (wide)' from the MedDRA version 22.1. Time to onset of the first episode of congestive heart failure was analyzed using a Kaplan-Meier approach. Participants who did not experience any congestive heart failure at the time of data-cut were censored at the date of the last attended visit whilst on-treatment (including visits up to and including 28 days after last dose of study treatment). Only treatment emergent congestive heart failure events are included. (NCT01572038)
Timeframe: From Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Months (Median) |
|---|
| Pertuzumab + Trastuzumab + Taxane | NA |
Time to Response for Participants With Best Overall Response of Complete Response or Partial Response, as Assessed by the Investigator Using RECIST v1.1
Time to response (TTR) was defined as the time from the first study treatment administration to the date of first confirmed response (CR or PR). TTR was analyzed using a Kaplan-Meier approach. Participants who did not have CR or PR were censored at the date of their last evaluable tumor assessment. Participants for whom no post-baseline tumor assessments were available were censored at Day 1. Responses according to RECIST v1.1 are defined as follows: CR = Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimetres (mm).; PR = At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT01572038)
Timeframe: From date of first study treatment until date of first confirmed response (CR or PR). The median (full range) duration of follow-up was 68.73 (0.03-87.29) months.
| Intervention | Months (Median) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 2.464 |
Number of Participants With Treatment-Emergent Adverse Events Leading to Discontinuation of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.2% of Participants by Preferred Term
Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs and the preferred terms are presented in descending order according to the total frequency of occurrence. If a participant experienced more than one event in a category, they were counted only once in that category. Discont. = discontinuation; Ptz = pertuzumab; Tax = taxane; Trz = trastuzumab (NCT01572038)
Timeframe: From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE, Pertuzumab Discontinuation (Ptz Discont) | Ptz Discont: Ejection Fraction Decreased | Ptz Discont: Cardiac Failure | Ptz Discont: Left Ventricular Dysfunction | Ptz Discont: Diarrhoea | Ptz Discont: Dyspnoea | Ptz Discont: Infusion Related Reaction | Ptz Discont: Sepsis | Ptz Discont: Neuropathy Peripheral | Ptz Discont: Hypersensitivity | Ptz Discont: General Physical Health Deterioration | Any TEAE, Trastuzumab Discontinuation(Trz Discont) | Trz Discont: Ejection Fraction Decreased | Trz Discont: Cardiac Failure | Trz Discont: Left Ventricular Dysfunction | Trz Discont: Diarrhoea | Trz Discont: Sepsis | Trz Discont: Dyspnoea | Trz Discont: Neuropathy Peripheral | Trz Discont: Hypersensitivity | Trz Discont: General Physical Health Deterioration | Any TEAE, Taxane Discontinuation (Tax Discont) | Tax Discont: Neuropathy Peripheral | Tax Discont: Peripheral Sensory Neuropathy | Tax Discont: Paraesthesia | Tax Discont: Diarrhoea | Tax Discont: Fatigue | Tax Discont: Asthenia | Tax Discont: Onycholysis | Tax Discont: Nail Toxicity | Tax Discont: Neurotoxicity | Tax Discont: Polyneuropathy | Tax Discont: Oedema Peripheral | Tax Discont: Febrile Neutropenia | Tax Discont: Neutropenia | Tax Discont: Dyspnoea | Tax Discont: Decreased Appetite | Tax Discont: Ejection Fraction Decreased | Tax Discont: General Physical Health Deterioration | Tax Discont: Mucosal Inflammation | Tax Discont: Rash | Tax Discont: Anaemia | Tax Discont: Arthralgia | Tax Discont: Drug Hypersensitivity | Tax Discont: Dysgeusia | Tax Discont: Nail Disorder | Tax Discont: Nail Dystrophy | Tax Discont: Skin Toxicity | Tax Discont: Pneumonia | Tax Discont: Sepsis | Tax Discont: Pleural Effusion | Tax Discont: Pneumonitis | Tax Discont: Cardiac Failure | Tax Discont: Myalgia |
|---|
| Pertuzumab + Trastuzumab + Taxane | 140 | 37 | 10 | 7 | 7 | 4 | 4 | 3 | 3 | 3 | 3 | 133 | 37 | 10 | 7 | 6 | 3 | 3 | 3 | 3 | 3 | 286 | 52 | 25 | 24 | 19 | 16 | 13 | 8 | 7 | 7 | 7 | 7 | 7 | 7 | 6 | 6 | 5 | 4 | 4 | 4 | 4 | 4 | 4 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 | 3 |
Number of Participants With Treatment-Emergent Adverse Events of Special Interest by Category and Preferred Term
Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. TEAEs of special interest included LVEF decreased, liver enzymes (ALT or AST) increased, and suspected transmission of infectious agent by the study drug. MedDRA version 22.1 was used to code AEs; preferred terms (PT) that are part of a given category are listed in the rows directly below each category within the results table. If a participant experienced more than one event in a category, they were counted only once in that category. (NCT01572038)
Timeframe: From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE of Special Interest | Decline in LVEF (Category) | Ejection Fraction Decreased (PT) | Left Ventricular Dysfunction (PT) | Cardiac Failure (PT) | Cardiac Failure Congestive (PT) | Elevated ALT or AST (Category) | Hepatic Failure (PT) |
|---|
| Pertuzumab + Trastuzumab + Taxane | 91 | 90 | 75 | 8 | 7 | 1 | 1 | 1 |
Number of Participants With Treatment-Emergent Adverse Events Leading to Dose Interruption of Study Treatment (Pertuzumab, Trastuzumab, or Taxane), Occurring in ≥0.5% of Participants by Preferred Term
Treatment-emergent adverse events (TEAEs) were adverse events (AEs) that started or worsened in severity on or after the first administration of study drug, up to and including 28 days after the last dose. The investigator graded all AEs for severity per NCI-CTCAE v4.0; if not listed, the AE was assessed as follows: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening/disabling; Grade 5 = death. The investigator determined whether an AE was related to study drug and independently assessed severity and seriousness of each AE. MedDRA version 22.1 was used to code AEs and the preferred terms are presented in descending order according to the total frequency of occurrence. If a participant experienced more than one event in a category, they were counted only once in that category. Interrupt. = interruption; Ptz = pertuzumab; Tax = taxane; Trz = trastuzumab (NCT01572038)
Timeframe: From Baseline until 28 days after, or 7 months after (only for serious AEs related to study drug), the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Any TEAE, Pertuzumab Interruption (Ptz Interrupt) | Ptz Interrupt: Ejection Fraction Decreased | Ptz Interrupt: Diarrhoea | Ptz Interrupt: Neutropenia | Ptz Interrupt: Pneumonia | Ptz Interrupt: Upper Respiratory Tract Infection | Ptz Interrupt: Pyrexia | Ptz Interrupt: Dyspnoea | Ptz Interrupt: Drug Hypersensitivity | Ptz Interrupt: Influenza | Ptz Interrupt: Asthenia | Ptz Interrupt: Neutrophil Count Decreased | Ptz Interrupt: Nasopharyngitis | Ptz Interrupt: Anaemia | Any TEAE, Trastuzumab Interruption (Trz Interrupt) | Trz Interrupt: Ejection Fraction Decreased | Trz Interrupt: Drug Hypersensitivity | Trz Interrupt: Diarrhoea | Trz Interrupt: Pyrexia | Trz Interrupt: Neutropenia | Trz Interrupt: Dyspnoea | Trz Interrupt: Pneumonia | Trz Interrupt: Chills | Trz Interrupt: Infusion Related Reaction | Trz Interrupt: Upper Respiratory Tract Infection | Trz Interrupt: Neutrophil Count Decreased | Trz Interrupt: Influenza | Trz Interrupt: Asthenia | Trz Interrupt: Vomiting | Trz Interrupt: Anaemia | Trz Interrupt: Nasopharyngitis | Any TEAE, Taxane Interruption (Tax Interrupt) | Tax Interrupt: Neutropenia | Tax Interrupt: Diarrhoea | Tax Interrupt: Leukopenia | Tax Interrupt: Dyspnoea | Tax Interrupt: Pyrexia | Tax Interrupt: Neutrophil Count Decreased | Tax Interrupt: Ejection Fraction Decreased | Tax Interrupt: Neuropathy Peripheral | Tax Interrupt: Nasopharyngitis | Tax Interrupt: Drug Hypersensitivity | Tax Interrupt: Fatigue | Tax Interrupt: Upper Respiratory Tract Infection | Tax Interrupt: Infusion Related Reaction | Tax Interrupt: Asthenia | Tax Interrupt: Erythema | Tax Interrupt: Pneumonia | Tax Interrupt: Flushing | Tax Interrupt: Hypersensitivity |
|---|
| Pertuzumab + Trastuzumab + Taxane | 334 | 51 | 21 | 17 | 14 | 13 | 11 | 11 | 9 | 8 | 8 | 8 | 7 | 7 | 386 | 52 | 31 | 20 | 18 | 17 | 17 | 14 | 13 | 13 | 12 | 8 | 7 | 7 | 7 | 7 | 7 | 354 | 46 | 30 | 17 | 15 | 14 | 14 | 13 | 13 | 10 | 10 | 10 | 9 | 9 | 9 | 8 | 7 | 7 | 7 |
Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to Normal Range Criteria
Clinical laboratory tests for hematology and coagulation parameters were performed at local laboratories. Laboratory toxicities were defined based on local laboratory normal ranges (for parameters with NCI-CTC grade not defined). Some laboratory parameters are bi-dimensional (i.e. can be graded in both the low and high direction). These parameters were split and presented in both directions. Baseline was defined as the last non-missing measurement taken prior to the first dose of study treatment (including unscheduled assessments). Values from all visits, including unscheduled visits, were included in the derivation of the worst post-baseline grade. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: was clinically significant (per investigator); was accompanied by clinical symptoms; resulted in a change in study treatment; or resulted in a medical intervention or a change in concomitant therapy. (NCT01572038)
Timeframe: Predose at each treatment cycle (1 cycle is 3 weeks) from Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Basophils (High): Normal to Normal | Basophils (High): Normal to Low | Basophils (High): Normal to High | Basophils (High): Low to Normal | Basophils (High): Low to Low | Basophils (High): Low to High | Basophils (High): High to Normal | Basophils (High): High to High | Basophils (High): Missing to Normal | Basophils (High): Missing to High | Basophils (High): Missing to Missing | Basophils (Low): Normal to Normal | Basophils (Low): Normal to Low | Basophils (Low): Normal to High | Basophils (Low): Low to Normal | Basophils (Low): Low to Low | Basophils (Low): Low to Missing | Basophils (Low): High to Normal | Basophils (Low): High to Low | Basophils (Low): High to High | Basophils (Low): Missing to Normal | Basophils (Low): Missing to Low | Basophils (Low): Missing to High | Basophils (Low): Missing to Missing | Eosinophils (High): Normal to Normal | Eosinophils (High): Normal to Low | Eosinophils (High): Normal to High | Eosinophils (High): Low to Normal | Eosinophils (High): Low to Low | Eosinophils (High): Low to High | Eosinophils (High): High to Normal | Eosinophils (High): High to High | Eosinophils (High): Missing to Normal | Eosinophils (High): Missing to Low | Eosinophils (High): Missing to High | Eosinophils (High): Missing to Missing | Eosinophils (Low): Normal to Normal | Eosinophils (Low): Normal to Low | Eosinophils (Low): Low to Normal | Eosinophils (Low): Low to Low | Eosinophils (Low): Low to High | Eosinophils (Low): High to Normal | Eosinophils (Low): High to Low | Eosinophils (Low): High to High | Eosinophils (Low): Missing to Normal | Eosinophils (Low): Missing to Low | Eosinophils (Low): Missing to Missing | Hematocrit (High): Normal to Normal | Hematocrit (High): Normal to Low | Hematocrit (High): Normal to High | Hematocrit (High): Normal to Missing | Hematocrit (High): Low to Normal | Hematocrit (High): Low to Low | Hematocrit (High): Low to High | Hematocrit (High): Low to Missing | Hematocrit (High): High to Normal | Hematocrit (High): High to High | Hematocrit (High): Missing to Normal | Hematocrit (High): Missing to High | Hematocrit (High): Missing to Missing | Hematocrit (Low): Normal to Normal | Hematocrit (Low): Normal to Low | Hematocrit (Low): Normal to Missing | Hematocrit (Low): Low to Normal | Hematocrit (Low): Low to Low | Hematocrit (Low): High to Normal | Hematocrit (Low): High to Low | Hematocrit (Low): Missing to Normal | Hematocrit (Low): Missing to Low | Hematocrit (Low): Missing to Missing | Monocytes (High): Normal to Normal | Monocytes (High): Normal to Low | Monocytes (High): Normal to High | Monocytes (High): Low to Normal | Monocytes (High): Low to Low | Monocytes (High): Low to High | Monocytes (High): High to Normal | Monocytes (High): High to Low | Monocytes (High): High to High | Monocytes (High): Missing to Normal | Monocytes (High): Missing to High | Monocytes (High): Missing to Missing | Monocytes (Low): Normal to Normal | Monocytes (Low): Normal to Low | Monocytes (Low): Normal to High | Monocytes (Low): Low to Normal | Monocytes (Low): Low to Low | Monocytes (Low): High to Normal | Monocytes (Low): High to Low | Monocytes (Low): High to High | Monocytes (Low): Missing to Normal | Monocytes (Low): Missing to Low | Monocytes (Low): Missing to High | Monocytes (Low): Missing to Missing | Red Blood Cells (High): Normal to Normal | Red Blood Cells (High): Normal to Low | Red Blood Cells (High): Normal to High | Red Blood Cells (High): Low to Normal | Red Blood Cells (High): Low to Low | Red Blood Cells (High): Low to High | Red Blood Cells (High): High to Normal | Red Blood Cells (High): High to High | Red Blood Cells (High): Missing to Normal | Red Blood Cells (High): Missing to Low | Red Blood Cells (High): Missing to High | Red Blood Cells (High): Missing to Missing | Red Blood Cells (Low): Normal to Normal | Red Blood Cells (Low): Normal to Low | Red Blood Cells (Low): Low to Normal | Red Blood Cells (Low): Low to Low | Red Blood Cells (Low): High to Normal | Red Blood Cells (Low): High to Low | Red Blood Cells (Low): High to High | Red Blood Cells (Low): Missing to Normal | Red Blood Cells (Low): Missing to Low | Red Blood Cells (Low): Missing to Missing | PTT (High): Normal to Normal | PTT (High): Normal to Low | PTT (High): Normal to High | PTT (High): Low to Normal | PTT (High): Low to Low | PTT (High): Low to High | PTT (High): High to High | PTT (High): Missing to Normal | PTT (High): Missing to Low | PTT (High): Missing to High | PTT (High): Missing to Missing | PTT (Low): Normal to Normal | PTT (Low): Normal to Low | PTT (Low): Low to Normal | PTT (Low): Low to Low | PTT (Low): High to Normal | PTT (Low): Missing to Normal | PTT (Low): Missing to Low | PTT (Low): Missing to High | PTT (Low): Missing to Missing |
|---|
| Pertuzumab + Trastuzumab + Taxane | 1020 | 3 | 261 | 16 | 1 | 5 | 11 | 38 | 21 | 7 | 53 | 1206 | 77 | 1 | 3 | 18 | 1 | 36 | 5 | 8 | 40 | 3 | 1 | 37 | 904 | 13 | 283 | 66 | 13 | 36 | 11 | 35 | 17 | 1 | 7 | 50 | 810 | 390 | 13 | 101 | 1 | 28 | 13 | 5 | 37 | 10 | 28 | 953 | 47 | 58 | 4 | 201 | 97 | 10 | 2 | 17 | 12 | 15 | 1 | 19 | 223 | 837 | 2 | 5 | 305 | 13 | 16 | 3 | 12 | 20 | 802 | 3 | 365 | 58 | 6 | 17 | 29 | 1 | 82 | 12 | 8 | 53 | 747 | 420 | 3 | 11 | 70 | 64 | 40 | 8 | 13 | 10 | 5 | 45 | 975 | 31 | 111 | 131 | 61 | 15 | 22 | 45 | 18 | 2 | 2 | 23 | 350 | 767 | 10 | 197 | 44 | 21 | 2 | 6 | 16 | 23 | 46 | 1 | 15 | 19 | 1 | 1 | 1 | 19 | 5 | 9 | 1319 | 46 | 16 | 3 | 18 | 1 | 20 | 6 | 5 | 1321 |
Number of Participants With Laboratory Abnormalities in Hematology and Coagulation Parameters: Shift From Baseline to the Worst Post-Baseline Grade According to NCI-CTC v4.0
Clinical laboratory tests for hematology and coagulation parameters were performed at local laboratories. Laboratory toxicities were defined based on NCI-CTC v4.0 from Grades 1 (least severe) to 4 (most severe). Some laboratory parameters are bi-dimensional (i.e. can be graded in both the low and high direction). These parameters were split and presented in both directions. Baseline was defined as the last non-missing measurement taken prior to the first dose of study treatment (including unscheduled assessments). Values from all visits, including unscheduled visits, were included in the derivation of the worst post-baseline grade. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: was clinically significant (per investigator); was accompanied by clinical symptoms; resulted in a change in study treatment; or resulted in a medical intervention or a change in concomitant therapy. (NCT01572038)
Timeframe: Predose at each treatment cycle (1 cycle is 3 weeks) from Baseline until 28 days after the last dose of study treatment. The median (full range) duration of exposure to any study treatment was 16.2 (0.0-86.4) months.
| Intervention | Participants (Count of Participants) |
|---|
| Absolute Neutrophil Count: Normal to Normal | Absolute Neutrophil Count: Normal to Grade 1 | Absolute Neutrophil Count: Normal to Grade 2 | Absolute Neutrophil Count: Normal to Grade 3 | Absolute Neutrophil Count: Normal to Grade 4 | Absolute Neutrophil Count: Normal to Missing | Absolute Neutrophil Count: Grade 1 to Normal | Absolute Neutrophil Count: Grade 1 to 1 | Absolute Neutrophil Count: Grade 1 to 2 | Absolute Neutrophil Count: Grade 1 to 3 | Absolute Neutrophil Count: Grade 2 to 1 | Absolute Neutrophil Count: Missing to Normal | Absolute Neutrophil Count: Missing to Grade 1 | Absolute Neutrophil Count: Missing to Grade 2 | Absolute Neutrophil Count: Missing to Grade 4 | Absolute Neutrophil Count: Missing to Missing | Hemoglobin (High): Normal to Normal | Hemoglobin (High): Normal to Grade 1 | Hemoglobin (High): Normal to Grade 3 | Hemoglobin (High): Normal to Missing | Hemoglobin (High): Grade 1 to Normal | Hemoglobin (High): Grade 1 to 1 | Hemoglobin (High): Grade 1 to Missing | Hemoglobin (High): Grade 2 to Normal | Hemoglobin (High): Missing to Normal | Hemoglobin (High): Missing to Missing | Hemoglobin (Low): Normal to Normal | Hemoglobin (Low): Normal to Grade 1 | Hemoglobin (Low): Normal to Grade 2 | Hemoglobin (Low): Normal to Grade 3 | Hemoglobin (Low): Normal to Missing | Hemoglobin (Low): Grade 1 to Normal | Hemoglobin (Low): Grade 1 to 1 | Hemoglobin (Low): Grade 1 to 2 | Hemoglobin (Low): Grade 1 to 3 | Hemoglobin (Low): Grade 1 to Missing | Hemoglobin (Low): Grade 2 to 1 | Hemoglobin (Low): Grade 2 to 2 | Hemoglobin (Low): Grade 2 to 3 | Hemoglobin (Low): Grade 2 to Missing | Hemoglobin (Low): Grade 3 to 1 | Hemoglobin (Low): Missing to Normal | Hemoglobin (Low): Missing to Grade 1 | Hemoglobin (Low): Missing to Grade 2 | Hemoglobin (Low): Missing to Missing | Lymphocytes (High): Normal to Normal | Lymphocytes (High): Normal to Grade 2 | Lymphocytes (High): Normal to Grade 3 | Lymphocytes (High): Normal to Missing | Lymphocytes (High): Grade 2 to Normal | Lymphocytes (High): Grade 2 to 2 | Lymphocytes (High): Grade 2 to 3 | Lymphocytes (High): Grade 3 to Normal | Lymphocytes (High): Grade 3 to 3 | Lymphocytes (High): Missing to Normal | Lymphocytes (High): Missing to Grade 2 | Lymphocytes (High): Missing to Missing | Lymphocytes (Low): Normal to Normal | Lymphocytes (Low): Normal to Grade 1 | Lymphocytes (Low): Normal to Grade 2 | Lymphocytes (Low): Normal to Grade 3 | Lymphocytes (Low): Normal to Grade 4 | Lymphocytes (Low): Normal to Missing | Lymphocytes (Low): Grade 1 to Normal | Lymphocytes (Low): Grade 1 to 1 | Lymphocytes (Low): Grade 1 to 2 | Lymphocytes (Low): Grade 1 to 3 | Lymphocytes (Low): Grade 1 to 4 | Lymphocytes (Low): Grade 1 to Missing | Lymphocytes (Low): Grade 2 to Normal | Lymphocytes (Low): Grade 2 to 1 | Lymphocytes (Low): Grade 2 to 2 | Lymphocytes (Low): Grade 2 to 3 | Lymphocytes (Low): Grade 2 to 4 | Lymphocytes (Low): Grade 2 to Missing | Lymphocytes (Low): Grade 3 to 1 | Lymphocytes (Low): Grade 3 to 2 | Lymphocytes (Low): Grade 3 to 3 | Lymphocytes (Low): Grade 3 to 4 | Lymphocytes (Low): Grade 3 to Missing | Lymphocytes (Low): Grade 4 to 2 | Lymphocytes (Low): Grade 4 to 3 | Lymphocytes (Low): Grade 4 to 4 | Lymphocytes (Low): Grade 4 to Missing | Lymphocytes (Low): Missing to Normal | Lymphocytes (Low): Missing to Grade 1 | Lymphocytes (Low): Missing to Grade 2 | Lymphocytes (Low): Missing to Grade 3 | Lymphocytes (Low): Missing to Missing | Platelet Count: Normal to Normal | Platelet Count: Normal to Grade 1 | Platelet Count: Normal to Grade 3 | Platelet Count: Normal to Grade 4 | Platelet Count: Normal to Missing | Platelet Count: Grade 1 to Normal | Platelet Count: Grade 1 to 1 | Platelet Count: Grade 1 to 2 | Platelet Count: Grade 1 to Missing | Platelet Count: Missing to Normal | Platelet Count: Missing to Grade 1 | White Blood Cells (High): Normal to Normal | White Blood Cells (High): Normal to Missing | White Blood Cells (High): Missing to Normal | White Blood Cells (High): Missing to Missing | White Blood Cells (Low): Normal to Normal | White Blood Cells (Low): Normal to Grade 1 | White Blood Cells (Low): Normal to Grade 2 | White Blood Cells (Low): Normal to Grade 3 | White Blood Cells (Low): Normal to Grade 4 | White Blood Cells (Low): Normal to Missing | White Blood Cells (Low): Grade 1 to Normal | White Blood Cells (Low): Grade 1 to 1 | White Blood Cells (Low): Grade 1 to 2 | White Blood Cells (Low): Grade 1 to 3 | White Blood Cells (Low): Grade 2 to Normal | White Blood Cells (Low): Grade 2 to 1 | White Blood Cells (Low): Grade 2 to 2 | White Blood Cells (Low): Grade 3 to Normal | White Blood Cells (Low): Grade 3 to 3 | White Blood Cells (Low): Missing to Normal | White Blood Cells (Low): Missing to Grade 1 | White Blood Cells (Low): Missing to Grade 2 | White Blood Cells (Low): Missing to Grade 3 | White Blood Cells (Low): Missing to Missing | International Normalized Ratio: Normal to Normal | International Normalized Ratio: Normal to Grade 1 | International Normalized Ratio: Normal to Grade 2 | International Normalized Ratio: Normal to Missing | International Normalized Ratio: Grade 1 to Normal | International Normalized Ratio: Grade 2 to 3 | International Normalized Ratio: Missing to Normal | International Normalized Ratio: Missing to Grade 1 | International Normalized Ratio: Missing to Grade 2 | International Normalized Ratio: Missing to Grade 3 | International Normalized Ratio: Missing to Missing |
|---|
| Pertuzumab + Trastuzumab + Taxane | 844 | 232 | 169 | 45 | 27 | 27 | 3 | 11 | 14 | 3 | 2 | 21 | 2 | 3 | 1 | 32 | 1327 | 29 | 1 | 26 | 28 | 5 | 2 | 1 | 14 | 3 | 257 | 648 | 198 | 10 | 21 | 2 | 109 | 128 | 12 | 4 | 5 | 18 | 3 | 3 | 1 | 3 | 7 | 4 | 3 | 1251 | 111 | 8 | 28 | 4 | 10 | 2 | 1 | 2 | 15 | 2 | 2 | 565 | 255 | 210 | 76 | 18 | 19 | 11 | 54 | 51 | 18 | 6 | 5 | 12 | 8 | 37 | 19 | 1 | 2 | 3 | 8 | 14 | 2 | 1 | 1 | 3 | 16 | 1 | 11 | 3 | 3 | 1 | 2 | 1222 | 149 | 1 | 2 | 26 | 15 | 16 | 1 | 2 | 1 | 1 | 1391 | 29 | 14 | 2 | 702 | 392 | 190 | 29 | 6 | 29 | 4 | 20 | 33 | 4 | 2 | 4 | 3 | 1 | 1 | 9 | 3 | 1 | 1 | 2 | 17 | 52 | 1 | 3 | 1 | 1 | 424 | 615 | 23 | 14 | 285 |
Part 2: Number of Participants Who Had Relationship Between MORAb-004 Exposures and Biomarker Levels
(NCT01574716)
Timeframe: Up to approximately 3 years
| Intervention | participants (Number) |
|---|
| Part 2: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel | 0 |
| Part 2: Placebo + Gemcitabine/Docetaxel | 0 |
Part 2: Overall Response Rate (ORR)
ORR was defined as the percentage of subjects with either a complete response (CR) or a partial response (PR) based on RECIST 1.1. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as at least a 30 percent (%) decrease in sum of diameters of target lesions, taking as reference the baseline sum of diameters. (NCT01574716)
Timeframe: From date of first dose until disease progression (up to approximately 3.5 years)
| Intervention | percentage of participants (Number) |
|---|
| Part 2: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel | 19.4 |
| Part 2: Placebo + Gemcitabine/Docetaxel | 20.0 |
Part 2: Overall Survival (OS)
OS was defined as the time (in months) from the date of randomization to the date of death, regardless of the cause. (NCT01574716)
Timeframe: From date of first dose until date of death from any cause (up to approximately 3.5 years)
| Intervention | months (Median) |
|---|
| Part 2: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel | 18.3 |
| Part 2: Placebo + Gemcitabine/Docetaxel | 21.1 |
Part 2: Radiologic Progression-free Survival (PFS)
PFS was defined as the time (in weeks) from the date of randomization to the date of first observation of disease progression according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) or date of death, regardless of the cause. (NCT01574716)
Timeframe: From date of first dose until date of first observation of disease progression, or death due to any cause (up to approximately 3 years)
| Intervention | weeks (Median) |
|---|
| Part 2: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel | 18.7 |
| Part 2: Placebo + Gemcitabine/Docetaxel | 24.1 |
Part 2: Radiologic Progression-free Survival Rate (PFR)
Radiologic progression-free survival rate was defined as the percentage of subjects achieving radiologic PFS at the pre-specified time points. (NCT01574716)
Timeframe: Weeks 12, 24, 48 and 52
| Intervention | percentage of participants (Number) |
|---|
| 12 weeks | 24 weeks | 48 weeks | 52 weeks |
|---|
| Part 2: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel | 57.6 | 43.3 | 24.5 | 20.8 |
,| Part 2: Placebo + Gemcitabine/Docetaxel | 61.8 | 51.0 | 25.2 | 21.4 |
Part 2: Symptomatic Progression-free Survival
PFS including symptomatic progression was defined as the time (in weeks) from the date of randomization to the date of the first observation of disease progression according to RECIST 1.1, symptomatic progression, or death due to any cause. (NCT01574716)
Timeframe: From date of first dose until date of first observation of disease progression, symptomatic progression, or death due to any cause (up to approximately 3 years)
| Intervention | weeks (Median) |
|---|
| Part 2: MORAb-004 8.0 mg/kg + Gemcitabine/Docetaxel | 18.1 |
| Part 2: Placebo + Gemcitabine/Docetaxel | 24.0 |
Average Score of Quality of Life
"To estimate the quality of life of patient with metastatic an/or locally advanced recurrent STS using the Quality of Life Questionnaire (QLQ-C30). The QLQ-C30 is scored on a scale from 0-100 with 0 indicating never and 100 indicating always in regard the the participants' experience of fatigue, nausea/vomiting, pain, disponae, insomnia, appetite loss, constipation, diarrhea, financial concerns at 4 time points through the study." (NCT01593748)
Timeframe: Baseline, Cycle 2, Cycle 6 and End of Treatment
| Intervention | score on a scale (Mean) |
|---|
| Fatigue at baseline | Nausea/Vommiting at baseline | Pain at baseline | Dysponae at baseline | Insomnia at baseline | Appetite loss at baseline | Constipation at baseline | Diarrhea at baseline | Financial at baseline | Fatigue at cycle 2 | Nausea/Vomitting at cycle 2 | Pain at cycle 2 | Dyspnoae at cycle 2 | Insomnia at cycle 2 | Appetite loss at cycle 2 | Constipation at cycle 2 | Diarrhea at cycle 2 | Financial at cycle 2 | Fatigue at cycle 6 | Nausea/vommiting at cycle 6 | Pain at cycle 6 | Dyspnoae at cycle 6 | Insomnia at cycle 6 | Appetite loss at cycle 6 | Constipation at cycle 6 | Diarrhea at cycle 6 | Financial at cycle 6 | Fatigue at end of study | Nausea/vomitting at end of study | Pain at end of study | Dysponae at end of study | Insomnia at end of study | Appetite loss at end of study | Constipation at end of study | Diarrhea at end of study | Financial at end of study |
|---|
| Experimental | 61.79 | 91.06 | 61.38 | 22.76 | 45.53 | 22.76 | 14.63 | 4.88 | 37.40 | 52.89 | 80.67 | 66.00 | 24.00 | 42.67 | 36.11 | 13.33 | 4.88 | 26.67 | 64.44 | 86.67 | 80.00 | 10.00 | 23.33 | 26.67 | 13.33 | 36.67 | 23.33 | 49.81 | 75.86 | 53.45 | 31.03 | 48.28 | 37.93 | 17.24 | 21.43 | 39.60 |
,| Standard of Care | 67.12 | 90.99 | 74.77 | 21.62 | 36.04 | 15.32 | 15.32 | 8.11 | 32.43 | 55.09 | 93.75 | 83.33 | 26.39 | 38.89 | 26.39 | 23.61 | 8.11 | 22.22 | 51.11 | 8.05 | 78.33 | 43.33 | 33.33 | 30.00 | 13.33 | 20.00 | 20.00 | 49.77 | 92.36 | 72.92 | 34.72 | 37.50 | 23.61 | 29.17 | 15.28 | 29.17 |
Rate of Participants With Grade 3 or Higher Toxicity
Toxicity is graded according to the CTCAE v 4. (NCT01593748)
Timeframe: 30 days post end of treatment
| Intervention | Participants (Count of Participants) |
|---|
| Experimental | 39 |
| Standard of Care | 39 |
Hazard Ratio
Hazard ratio is defined as the rate of survival in the experimental group versus the standard of care group. A hazard ratio of greater than one or less than one means that survival was better in one of the groups. (NCT01593748)
Timeframe: minimum of 18 months
| Intervention | hazard ratio (Number) |
|---|
| Experimental | 1.2 |
| Standard of Care | NA |
Average Number of Months of Progression-free Survival
To estimate the PFS of the combination of G+P or G+T in patients with metastatic and/or locally advanced or recurrent STS. Progression free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. (NCT01593748)
Timeframe: minimum of 18 months
| Intervention | months (Median) |
|---|
| Experimental | 4.1 |
| Standard of Care | 4.1 |
Assessment of Total Number of Survival Events With Comparison of Group Arms
The number of deaths in both arms will be assessed. (NCT01603420)
Timeframe: at study closure (22 months)
| Intervention | participants (Number) |
|---|
| Radiation + 24mo LHRH | 0 |
| Radiation + Chemo + 6mo LHRH | 0 |
Assessment of Total Number of Local/Distant Failures
The total number of local/distant failures will be assessed. (NCT01603420)
Timeframe: at time of study closure (22 months)
| Intervention | participants (Number) |
|---|
| Radiation + 24mo LHRH | 0 |
| Radiation + Chemo + 6mo LHRH | 0 |
Assessment of Total Number of Biochemical Failure Events
The number of biochemical failure events will be assessed on both arms. (NCT01603420)
Timeframe: at study closure (22 months)
| Intervention | participants (Number) |
|---|
| Radiation + 24mo LHRH | 0 |
| Radiation + Chemo + 6mo LHRH | 0 |
Assessment of Number of Grade 2 or Higher Genitourinary (GU) and Gastrointestinal (GI) Adverse Events
Assessment will be performed using CTCAE v 4 criteria. (NCT01603420)
Timeframe: at 6 months
| Intervention | incidences (Number) |
|---|
| Radiation + 24mo Luteinizing Hormone-releasing Hormone (LHRH) | 0 |
| Radiation + Chemo + 6mo Luteinizing Hormone-releasing Hormone | 1 |
Phase 2 - Cumulative Number of Incidences of Grade 3 or Higher Adverse Events.
"Assessment will be performed using CTCAE v4 criteria.~This study was terminated prior to the time frame of 2 years being reached. Therefore, this outcome was assessed at time of study closure (22 months)." (NCT01603420)
Timeframe: 2 years
| Intervention | events (Number) |
|---|
| Radiation + 24mo LHRH | 0 |
| Radiation + Chemo + 6mo LHRH | 0 |
Assessment of Total Number of Salvage Androgen Deprivation Use With Comparison of Arms.
The total number of subjects with salvage androgen deprivation use will be assessed. (NCT01603420)
Timeframe: At study closure (22 months)
| Intervention | participants (Number) |
|---|
| Radiation + 24mo LHRH | 0 |
| Radiation + Chemo + 6mo LHRH | 0 |
Phase 2 - Assessment of Number of Freedom From Failure Events in the Chemotherapy Arm
"Measurement of Freedom from Failure i.e. the first occurence of clinical failure (local recurrence, regional recurrence, or distant metastasis), biochemical failure by the Phoenix definition (Prostate Specific Antigen [PSA] > = 2 ng/ml over the nadir PSA discounting bounces per the investigators discretion), or the start of salvage therapy including androgen deprivation.~This study was terminated prior to the time frame of 2 years being reached. Therefore, this outcome was assessed at time of study closure (22 months)." (NCT01603420)
Timeframe: No failures were reported at the time of study termination (22 months). This outcome was originally written to assess failure at 2 years. However, that end point was not reached.
| Intervention | failure events (Number) |
|---|
| Radiation + 24mo Luteinizing Hormone-releasing Hormone (LHRH) | 0 |
| Radiation + Chemo + 6mo Luteinizing Hormone-releasing Hormone | 0 |
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
| Intervention | score on a scale (Median) |
|---|
| EATING- Prior to treatment | EATING- 6 months | EATING- 12 months | EATING- 24 months |
|---|
| Active Comparator Arm | 91.7 | 83.3 | 83.3 | 95.8 |
,| Platinum/Docetaxal + AT-101 | 83.3 | 75 | 83.3 | 77.1 |
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
| Intervention | percentage of Patients (Number) |
|---|
| Platinum/Docetaxal + AT-101 | 61 |
| Active Comparator Arm | 44 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Platinum/Docetaxal + AT-101 | 27 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Platinum/Docetaxal + AT-101 | 27 |
| Active Comparator Arm | 12 |
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
| Intervention | percentage of participants (Number) |
|---|
| Platinum/Docetaxal + AT-101 | 55 |
| Active Comparator Arm | 65 |
Progression-free Survival (PFS)
Progression-free survival is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first. PFS is defined as the number of months from the date of first dose of study drug to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. (NCT01639131)
Timeframe: 9 months
| Intervention | months (Median) |
|---|
| Gemcitabine and Docetaxel | 1.79 |
Response Rate
The Response Rate is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. (NCT01639131)
Timeframe: 9 months
| Intervention | participants (Number) |
|---|
| Gemcitabine and Docetaxel | 0 |
Overall Survival With Gemcitabine and Docetaxel Combination Therapy
Overall survival is the time from the start of first dose of study drug to death. OS will be measured from date of first dose of a study drug until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. (NCT01639131)
Timeframe: 62 months
| Intervention | months (Median) |
|---|
| Gemcitabine and Docetaxel | 15.67 |
Progression Free Survival (PFS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants
PFS time was measured for all randomized participants grouped by their baseline PD-L1 expression levels. PFS was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator per RECIST v1.1 criteria, or death due to any cause. The PFS curves were estimated using KM method. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started subsequent anti-cancer therapy (including on-treatment palliative radiotherapy of non-target bone lesions or CNS lesions) without a prior reported progression were censored at the last evaluable tumor assessment prior to subsequent anti-cancer therapy. (NCT01642004)
Timeframe: From the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 103 months
| Intervention | Months (Median) |
|---|
| PD-L1 expression >= 5% | PD-L1 expression < 5% | PD-L1 not quantifiable at baseline |
|---|
| Docetaxel | 3.06 | 2.92 | 2.23 |
,| Nivolumab | 5.06 | 2.23 | 5.39 |
Overall Survival (OS) Time in Months by Baseline PD-L1 Expression for All Randomized Participants
OS was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. (NCT01642004)
Timeframe: From the date of randomization to the date of death from any cause, up to approximately 103 months
| Intervention | Months (Median) |
|---|
| PD-L1 expression >= 5% | PD-L1 expression < 5% | PD-L1 not quantifiable at baseline |
|---|
| Docetaxel | 6.37 | 6.14 | 5.06 |
,| Nivolumab | 9.95 | 8.54 | 9.41 |
Overall Survival (OS) Rate in All Randomized Participants - Extended Collection
The overall survival rate is the probability that a participant will be alive at the specified timepoints following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates. (NCT01642004)
Timeframe: From the date of randomization up to the specified timepoints, up to 84 months
| Intervention | Percent probability of OS (Number) |
|---|
| 6 months | 12 months | 18 months | 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Docetaxel | 50.4 | 24.1 | 12.4 | 8.0 | 5.8 | 4.4 | 3.6 | 2.7 | 0.0 |
,| Nivolumab | 63.7 | 42.2 | 28.1 | 23.0 | 15.6 | 13.1 | 12.3 | 11.4 | 9.6 |
Overall Survival (OS) Rate in All Randomized Participants
The overall survival rate is the probability that a participant will be alive at 6, 12, and 18 months following randomization. Overall survival was defined as the time between the date of randomization and the date of death as a result of any cause. Survival rates were determined via Kaplan-Meier estimates. (NCT01642004)
Timeframe: Randomization to 18 months post-randomization, up to June 2015
| Intervention | Percent probability of OS (Number) |
|---|
| 6 months | 12 months | 18 months |
|---|
| Docetaxel | 50.7 | 24.3 | 12.5 |
,| Nivolumab | 63.7 | 42.2 | 28.1 |
Progression-Free Survival (PFS) Time in Months for All Randomized Participants
PFS was defined as the time from the date of randomization to the date of the first documented tumor progression as determined by the investigator per RECIST v1.1 criteria, or death due to any cause. Participants underwent radiographic tumor assessments every 6 weeks (+/- 5 days) from week 9 (+/- 5 days) for the first year on treatment, then every 12 weeks after the first year on treatment until documented disease progression. The PFS curves were estimated using KM method. Two-sided 95% CI for median PFS were computed by Brookmeyer and Crowley method (using log-log transformation). Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative RT of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy. (NCT01642004)
Timeframe: From randomization up to the first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 103 months
| Intervention | Months (Median) |
|---|
| Nivolumab | 3.48 |
| Docetaxel | 2.83 |
Objective Response Rate (ORR) by Baseline PD-L1 Expression for All Randomized Participants
ORR was reported for all randomized participants grouped by their baseline PD-L1 expression level. ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. 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. CIs were computed using the Clopper and Pearson method. (NCT01642004)
Timeframe: From the date of randomization up to the date of objectively documented progression, up to approximately 103 months
| Intervention | Percentage of participants (Number) |
|---|
| PD-L1 expression >= 5% | PD-L1 expression < 5% | PD-L1 not quantifiable at baseline |
|---|
| Docetaxel | 7.7 | 11.6 | 3.4 |
,| Nivolumab | 21.4 | 14.7 | 38.9 |
Progression Free Survival Rate (PFSR)
PFSR was defined as the percentage of participants who did not experience disease progression or death from any cause at a given time point following randomization. Progression was assessed by investigators according to RECIST v1.1. Participants who did not progress or die were censored on the date of their last evaluable tumor assessment. Participants who started any subsequent anti-cancer therapy (including on-treatment palliative radiation therapy (RT) of non-target bone lesions or CNS lesions) without a prior reported progression were to be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy. (NCT01642004)
Timeframe: From randomization to specified timepoints, up to 84 months
| Intervention | Percentage of participants (Number) |
|---|
| 6 months | 12 months | 18 months | 24 months | 36 months | 48 months | 60 months | 72 months | 84 months |
|---|
| Docetaxel | 22.6 | 7.2 | 1.8 | NA | NA | NA | NA | NA | NA |
,| Nivolumab | 38.4 | 21.0 | 15.87 | 14.8 | 11.0 | 8.9 | 8.9 | 7.6 | 6.1 |
Time To Response (TTR) in Months for All Confirmed Responders
Time to Response (TTR) for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed 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.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. (NCT01642004)
Timeframe: From the date of randomization to the date of the first confirmed response, up to approximately 12 months
| Intervention | Months (Median) |
|---|
| Nivolumab | 2.23 |
| Docetaxel | 2.09 |
Duration of Objective Response (DOR) in Months for All Confirmed Responders
DOR was defined as the time from the date of first confirmed response to the date of the first documented tumor progression (per RECIST v1.1), as determined by the investigator, or death due to any cause, whichever occurred first. DOR was evaluated only for confirmed responders (i.e. participants with confirmed CR or PR). 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. Participants who neither progressed nor died were censored on the date of their last evaluable tumor assessment. (NCT01642004)
Timeframe: From the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 94 months
| Intervention | Months (Median) |
|---|
| Nivolumab | 24.51 |
| Docetaxel | 8.41 |
Number of Deaths From Any Cause in All Randomized Participants at Primary Endpoint
The number of participants who died from any cause was reported for each arm. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths. (NCT01642004)
Timeframe: Randomization until 199 deaths, up to November 2014, approximately 25 months
| Intervention | Participants (Number) |
|---|
| Nivolumab | 86 |
| Docetaxel | 113 |
Objective Response Rate (ORR) in All Randomized Participants
ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). BOR was defined as the best investigator-assessed response designation, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or the date of subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of non-target bone lesions or Central Nervous System (CNS) lesions), whichever occurred first. 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. CIs were computed using the Clopper and Pearson method. (NCT01642004)
Timeframe: From the date of randomization up to the date of objectively documented progression, up to approximately 103 months
| Intervention | Percentage of participants (Number) |
|---|
| Nivolumab | 20.0 |
| Docetaxel | 8.8 |
Overall Survival (OS) Time in Months for All Randomized Participants - Extended Collection
OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Survival follow-up analysis occurred at the end of the study. (NCT01642004)
Timeframe: From the date of first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first, up to approximately 103 months
| Intervention | Months (Median) |
|---|
| Nivolumab | 9.23 |
| Docetaxel | 6.01 |
Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint
OS was defined as the time between the date of randomization and the date of death from any cause. Participants were censored at the date they were last known to be alive. Median OS time was calculated using Kaplan-Meier (KM) method. Hazard ratio (HR) and the corresponding Confidence Interval (CI) were estimated in a stratified Cox proportional hazards model for distribution of OS in each randomized arm. Interim analysis (Primary Endpoint) was planned to occur after at least 196 deaths, with the actual analysis occurring at 199 deaths. (NCT01642004)
Timeframe: Randomization until 199 deaths, up to November 2014, approximately 25 months
| Intervention | months (Median) |
|---|
| Nivolumab | 9.23 |
| Docetaxel | 6.01 |
Progression Free Survival (PFS)
Compared PFS between the treatment of AUY922 to comparators Pemetrexed or Docetaxel. Progression-free survival (PFS) based on local investigator assessment per RECIST 1.1 was the time from date of randomization/start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient had not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progression was 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 (NCT01646125)
Timeframe: 16 months
| Intervention | Months (Median) |
|---|
| AUY922 Arm | 1.5 |
| Chemotherapy Arm | 2.3 |
Overall Response Rate (ORR)
ORR was to be compared between treatment arms. The ORR was to be based on local investigator assessment per Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST 1.1). Per this criteria 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.This outcome measure was originally planned to be analyzed up to 24 months. The DMC recommendation at the IA was to stop the study for futility. As a result, collection of all the efficacy assessments was stopped at that time. (NCT01646125)
Timeframe: 16 months
| Intervention | Participants (Number) |
|---|
| Complete Response (CR) | Partial Response (PR) | ORR (CR + PR) |
|---|
| AUY922 Arm | 0 | 3 | 3 |
,| Chemotherapy Arm | 0 | 2 | 2 |
Number of Participants With Adverse Events
Adverse events classified according to NCI CTCAE version 4 (NCT01652469)
Timeframe: Same as primary outcome: 24 months
| Intervention | Participants (Count of Participants) |
|---|
| Experienced AE/SAE | No AE/SAE | Experienced SAE |
|---|
| A: Erlotinib | 36 | 2 | 7 |
,| B: Docetaxel | 39 | 2 | 19 |
Progression-free Survival
"Time from the date of randomization until documented progression or death without documented progression.~Assessment of Progressive Disease (PD) based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) Target lesions: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).~Non-target lesions:Unequivocal progression of existing non-target lesions. (Note:the appearance of one or more new lesions is also considered progression). To achieve 'unequivocal progression', there must be an overall level of substantial worsening in non-target disease such that,even in presence of SD or PR in target disease, the overall tumour burden has increased sufficiently" (NCT01652469)
Timeframe: The combined run in period, treatment and follow-up for PFS is expected to extend the study duration to a total of 24 months.
| Intervention | months (Median) |
|---|
| A: Erlotinib | 1.6 |
| B: Docetaxel | 3.0 |
Overall Survival
Defined as time from the date of randomization until death from any cause. (NCT01652469)
Timeframe: All patients will be followed for survival status every 12 weeks up to 24 months after the last patient is randomized
| Intervention | months (Median) |
|---|
| A: Erlotinib | 7.1 |
| B: Docetaxel | 7.1 |
Volume of Distribution at Steady State (Vss) of CP-751,871 in Cycle 1
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | mL/kg (Mean) |
|---|
| CP-751,871 0.4 mg/kg + Docetaxel | 43.3 |
| CP-751,871 0.8 mg/kg + Docetaxel | 40.1 |
| CP-751,871 1.5 mg/kg + Docetaxel | 52.9 |
| CP-751,871 3 mg/kg + Docetaxel | 83.2 |
| CP-751,871 10 mg/kg + Docetaxel | 67.5 |
| CP-751,871 20 mg/kg + Docetaxel | 37.5 |
Plasma Decay Half-Life (t1/2) of CP-751,871 in Cycle 1
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | hr (Mean) |
|---|
| CP-751,871 0.4 mg/kg + Docetaxel | 68.5 |
| CP-751,871 0.8 mg/kg + Docetaxel | 97.4 |
| CP-751,871 1.5 mg/kg + Docetaxel | 151 |
| CP-751,871 3 mg/kg + Docetaxel | 150 |
| CP-751,871 10 mg/kg + Docetaxel | 224 |
| CP-751,871 20 mg/kg + Docetaxel | 174 |
Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 4
Maximum Observed Plasma Concentration (Cmax) divided by dose (NCT01653158)
Timeframe: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng/mL/(mg/m^2) (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 35.3 |
Dose Normalized Maximum Observed Plasma Concentration (Cmax(dn)) of Docetaxel in Cycle 1
Maximum Observed Plasma Concentration (Cmax) divided by dose (NCT01653158)
Timeframe: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng/mL/(mg/m^2) (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 35.4256 |
Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 4
Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion) (NCT01653158)
Timeframe: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng*hr/mL (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 2526.19 |
Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) of CP-751,871 in Cycle 4
Area under the plasma concentration versus time curve (AUC) from time zero to tau, the dosing interval, where tao is the actual time of the predose sample for the next cycle. (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
| Intervention | mg*hr/L (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 36.1 |
| CP-751,871 0.4 mg/kg + Docetaxel | 745 |
| CP-751,871 0.8 mg/kg + Docetaxel | 2978 |
| CP-751,871 1.5 mg/kg + Docetaxel | 11802 |
| CP-751,871 3 mg/kg + Docetaxel | 26329 |
| CP-751,871 6 mg/kg + Docetaxel | 55466 |
| CP-751,871 10 mg/kg + Docetaxel | 65711 |
| CP-751,871 20 mg/kg + Docetaxel | 233578 |
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of CP-751,871 in Cycle 1
Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - inf). It is obtained from AUC (0 - t) plus AUC (t - inf). (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | mg*hr/L (Mean) |
|---|
| CP-751,871 0.4 mg/kg + Docetaxel | 949 |
| CP-751,871 0.8 mg/kg + Docetaxel | 2744 |
| CP-751,871 1.5 mg/kg + Docetaxel | 6532 |
| CP-751,871 3 mg/kg + Docetaxel | 7799 |
| CP-751,871 10 mg/kg + Docetaxel | 47711 |
| CP-751,871 20 mg/kg + Docetaxel | 136026 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | mg*hr/L (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 22.3 |
| CP-751,871 0.4 mg/kg + Docetaxel | 673 |
| CP-751,871 0.8 mg/kg + Docetaxel | 1685 |
| CP-751,871 1.5 mg/kg + Docetaxel | 4568 |
| CP-751,871 3 mg/kg + Docetaxel | 10712 |
| CP-751,871 6 mg/kg + Docetaxel | 26215 |
| CP-751,871 10 mg/kg + Docetaxel | 39724 |
| CP-751,871 20 mg/kg + Docetaxel | 78106 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of CP-751,871 in Cycle 4
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
| Intervention | mg*hr/L (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 20.6 |
| CP-751,871 0.4 mg/kg + Docetaxel | 521 |
| CP-751,871 0.8 mg/kg + Docetaxel | 1728 |
| CP-751,871 1.5 mg/kg + Docetaxel | 11802 |
| CP-751,871 3 mg/kg + Docetaxel | 26329 |
| CP-751,871 6 mg/kg + Docetaxel | 55466 |
| CP-751,871 10 mg/kg + Docetaxel | 45521 |
| CP-751,871 20 mg/kg + Docetaxel | 197090 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) (NCT01653158)
Timeframe: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng*hr/mL (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 2770.71 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Docetaxel in Cycle 4
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) (NCT01653158)
Timeframe: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng*hr/mL (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 2438.34 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 1
(NCT01653158)
Timeframe: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | hr (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 0.9179 |
Observed Concentration of CP-751,871 at Day 22 (Cday22) of Cycle 1 and 4
Cday22 is the measured CP-751,871 plasma concentration in blood sample collected at Day 22. (NCT01653158)
Timeframe: Cycle 1: 30 minutes prior to the Cycle 2 CP-751,871 infusion (this is Day 22 for Cycle 1); Cycle 4: 30 minutes prior to the Cycle 5 CP-751,871 infusion (this is Day 22 for Cycle 4)
| Intervention | mg/L (Mean) |
|---|
| Day 22 of Cycle 1 | Day 22 of Cycle 4 |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 0 | 0 |
,| CP-751,871 0.4 mg/kg + Docetaxel | 0 | 0 |
,| CP-751,871 0.8 mg/kg + Docetaxel | 0.185 | 0.144 |
,| CP-751,871 1.5 mg/kg + Docetaxel | 2.11 | 12.5 |
,| CP-751,871 10 mg/kg + Docetaxel | 37.7 | 79.3 |
,| CP-751,871 20 mg/kg + Docetaxel | 84.5 | 199 |
,| CP-751,871 3 mg/kg + Docetaxel | 9.07 | 32.2 |
,| CP-751,871 6 mg/kg + Docetaxel | 30.4 | 47.2 |
Area Under the Curve From Time Zero (Day 1) to Day 22 (AUC(0-d22)) of CP-751,871 in Cycle 1
Area under the plasma concentration versus time curve (AUC) from time zero (Day 1) to Day 22, where Day 22 is the nominal time (504 hours) of the predose sample for the next cycle. (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | mg*hr/L (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 38.4 |
| CP-751,871 0.4 mg/kg + Docetaxel | 1045 |
| CP-751,871 0.8 mg/kg + Docetaxel | 2040 |
| CP-751,871 1.5 mg/kg + Docetaxel | 5026 |
| CP-751,871 3 mg/kg + Docetaxel | 10570 |
| CP-751,871 6 mg/kg + Docetaxel | 26215 |
| CP-751,871 10 mg/kg + Docetaxel | 38160 |
| CP-751,871 20 mg/kg + Docetaxel | 84916 |
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 4
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose (NCT01653158)
Timeframe: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng•hr/mL/(mg/m^2) (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 35.16 |
Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 1
(NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | mg/L (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 1.34 |
| CP-751,871 0.4 mg/kg + Docetaxel | 7.81 |
| CP-751,871 0.8 mg/kg + Docetaxel | 17.9 |
| CP-751,871 1.5 mg/kg + Docetaxel | 33.4 |
| CP-751,871 3 mg/kg + Docetaxel | 57.7 |
| CP-751,871 6 mg/kg + Docetaxel | 129 |
| CP-751,871 10 mg/kg + Docetaxel | 205 |
| CP-751,871 20 mg/kg + Docetaxel | 382 |
Area Under the Curve From Time Zero to 25 Hours Postdose (AUC25) of Docetaxel in Cycle 1
Area under the plasma concentration versus time curve (AUC) from time zero to 25 hours post dose, the nominal time of the last sample (24 hours after end of infusion) (NCT01653158)
Timeframe: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | nanogram*hour/millilitre (ng*hr/mL) (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 2852.11 |
Dose Normalized Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast(dn)) of Docetaxel in Cycle 1
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) divided by dose (NCT01653158)
Timeframe: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng•hr/mL/(mg/m^2) (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 36.9428 |
Observed Accumulation Ratio (Rac) of CP-751,871
AUCtao of Cycle 4 divided by AUC(0-d22) of Cycle 1 (NCT01653158)
Timeframe: 30 minutes prior to CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of CP-751,871 infusion; and 30 minutes prior to the next cycle CP-751,871 infusion (Day 22) in Cycle 1 and Cycle 4
| Intervention | Ratio (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 0.852 |
| CP-751,871 0.4 mg/kg + Docetaxel | 0.714 |
| CP-751,871 0.8 mg/kg + Docetaxel | 1.48 |
| CP-751,871 1.5 mg/kg + Docetaxel | 1.50 |
| CP-751,871 3 mg/kg + Docetaxel | 2.16 |
| CP-751,871 6 mg/kg + Docetaxel | 2.04 |
| CP-751,871 10 mg/kg + Docetaxel | 1.95 |
| CP-751,871 20 mg/kg + Docetaxel | 2.00 |
Recommended Phase 2 Dose (RP2D)
(NCT01653158)
Timeframe: Cycle 1 Day 1 through Cycle 1 Day 21
| Intervention | mg/kg (Number) |
|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | 20 |
Systemic Clearance (CL) of CP-751,871 in Cycle 1
CL is a quantitative measure of the rate at which a drug substance is removed from the body. (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | mL/day/kg (Mean) |
|---|
| CP-751,871 0.4 mg/kg + Docetaxel | 10.1 |
| CP-751,871 0.8 mg/kg + Docetaxel | 7.00 |
| CP-751,871 1.5 mg/kg + Docetaxel | 6.67 |
| CP-751,871 3 mg/kg + Docetaxel | 9.23 |
| CP-751,871 10 mg/kg + Docetaxel | 5.17 |
| CP-751,871 20 mg/kg + Docetaxel | 3.53 |
Systemic Clearance (CL) of CP-751,871 in Cycle 4
CL is a quantitative measure of the rate at which a drug substance is removed from the body. (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
| Intervention | mL/day/kg (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 70.6 |
| CP-751,871 0.4 mg/kg + Docetaxel | 12.90 |
| CP-751,871 0.8 mg/kg + Docetaxel | 6.84 |
| CP-751,871 1.5 mg/kg + Docetaxel | 3.05 |
| CP-751,871 3 mg/kg + Docetaxel | 2.74 |
| CP-751,871 6 mg/kg + Docetaxel | 2.68 |
| CP-751,871 10 mg/kg + Docetaxel | 4.01 |
| CP-751,871 20 mg/kg + Docetaxel | 2.70 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 1
(NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | hr (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 1.54 |
| CP-751,871 0.4 mg/kg + Docetaxel | 8.76 |
| CP-751,871 0.8 mg/kg + Docetaxel | 1.70 |
| CP-751,871 1.5 mg/kg + Docetaxel | 9.41 |
| CP-751,871 3 mg/kg + Docetaxel | 1.98 |
| CP-751,871 6 mg/kg + Docetaxel | 3.21 |
| CP-751,871 10 mg/kg + Docetaxel | 11.1 |
| CP-751,871 20 mg/kg + Docetaxel | 8.67 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) of CP-751,871 in Cycle 4
(NCT01653158)
Timeframe: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
| Intervention | hr (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 1.53 |
| CP-751,871 0.4 mg/kg + Docetaxel | 1.65 |
| CP-751,871 0.8 mg/kg + Docetaxel | 1.59 |
| CP-751,871 1.5 mg/kg + Docetaxel | 2.25 |
| CP-751,871 3 mg/kg + Docetaxel | 11.1 |
| CP-751,871 6 mg/kg + Docetaxel | 3.23 |
| CP-751,871 10 mg/kg + Docetaxel | 9.68 |
| CP-751,871 20 mg/kg + Docetaxel | 5.97 |
Number of Participants With the Occurrence of Human Anti-human Antibody (HAHA) Response to CP-751,871
The development of HAHA is considered clinically relevant when temporally associated to the onset of adverse events or a significant decrease in the plasma concentrations of CP-751,871. The positive value is defined as ≥3.32. (NCT01653158)
Timeframe: 30 minutes predose at each cycle, End of Study (28 days after the last CP-751,871 infusion), and 150 days after the last CP-751,871 infusion
| Intervention | Participants (Number) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 0 |
| CP-751,871 0.4 mg/kg + Docetaxel | 0 |
| CP-751,871 0.8 mg/kg + Docetaxel | 0 |
| CP-751,871 1.5 mg/kg + Docetaxel | 0 |
| CP-751,871 3 mg/kg + Docetaxel | 0 |
| CP-751,871 6 mg/kg + Docetaxel | 0 |
| CP-751,871 10 mg/kg + Docetaxel | 0 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Docetaxel in Cycle 4
(NCT01653158)
Timeframe: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | hr (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 0.8066 |
Volume of Distribution (Vz) of CP-751,871 in Cycle 1
Volume of distribution is 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. (NCT01653158)
Timeframe: 30 minutes prior to the Cycle 1 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 1 CP-751,871 infusion; and 30 minutes prior to the Cycle 2 CP-751,871 infusion (Day 22)
| Intervention | mL/kg (Mean) |
|---|
| CP-751,871 0.4 mg/kg + Docetaxel | 41.7 |
| CP-751,871 0.8 mg/kg + Docetaxel | 40.9 |
| CP-751,871 1.5 mg/kg + Docetaxel | 55.1 |
| CP-751,871 3 mg/kg + Docetaxel | 83.1 |
| CP-751,871 10 mg/kg + Docetaxel | 67.9 |
| CP-751,871 20 mg/kg + Docetaxel | 36.8 |
Maximum Tolerated Dose (MTD)
(NCT01653158)
Timeframe: Cycle 1 Day 1 through Cycle 1 Day 21
| Intervention | mg/kg (Number) |
|---|
| CP-751,871 0.1-20 mg/kg + Docetaxel | NA |
Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 4
(NCT01653158)
Timeframe: 30 minutes before CP-751,871 infusion; 1 hour after the end of CP-751,871 infusion; 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng/mL (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 2430 |
Maximum Observed Plasma Concentration (Cmax) of Docetaxel in Cycle 1
(NCT01653158)
Timeframe: 30 minutes before docetaxel infusion; 30 and 50 minutes after the start of docetaxel infusion; and 30 minutes and 1, 3, 8, and 24 hours after the end of docetaxel infusion
| Intervention | ng/mL (Mean) |
|---|
| CP-751,871 20 mg/kg + Docetaxel | 2656.92 |
Maximum Observed Plasma Concentration (Cmax) of CP-751,871 in Cycle 4
(NCT01653158)
Timeframe: 30 minutes prior to the Cycle 4 CP-751,871 infusion; 1 hour, and 1 (Day 2), 3 (Day 4) and 7 (Day 8) days post end of the Cycle 4 CP-751,871 infusion; and 30 minutes prior to the Cycle 5 CP-751,871 infusion (Day 22)
| Intervention | mg/L (Mean) |
|---|
| CP-751,871 0.1 mg/kg + Docetaxel | 1.29 |
| CP-751,871 0.4 mg/kg + Docetaxel | 6.91 |
| CP-751,871 0.8 mg/kg + Docetaxel | 17.8 |
| CP-751,871 1.5 mg/kg + Docetaxel | 54.7 |
| CP-751,871 3 mg/kg + Docetaxel | 103 |
| CP-751,871 6 mg/kg + Docetaxel | 188 |
| CP-751,871 10 mg/kg + Docetaxel | 311 |
| CP-751,871 20 mg/kg + Docetaxel | 658 |
Incidence of Febrile Neutropenia
Neutropenic fever was anticipated to be a clinically significant toxicity that would limit the maximal density of TC therapy. (NCT01671319)
Timeframe: Up to 10 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Dose Dense TC + Pegfilgrastim | 1 |
Feasibility for Dose-dense TC Therapy: Number of Participants Receiving at Least 90% of Total Dose of Therapy
Evaluate feasibility of delivering 4 cycles (1 cycle = 2 weeks) of docetaxel and cyclophosphamide (TC) on a dose-dense (q2week) schedule with pegfilgrastim support. This regimen will be referred to as dose-dense (dd)TC. Feasibility defined by at least 60% of patients receiving 90% of the total dose of therapy within 10 weeks. (NCT01671319)
Timeframe: 4 cycles each 2 weeks in length for a total of 8 weeks, up to 10 weeks
| Intervention | participants (Number) |
|---|
| Dose Dense TC + Pegfilgrastim | 37 |
Overall Survival
Compare overall survival of participants in both treatment arms. (NCT01671332)
Timeframe: Up to 50 months
| Intervention | months (Median) |
|---|
| Docetaxel | 5.3 |
| Docetaxel Plus Suramin | 4.1 |
Number of Participants With Toxicity/Adverse Events From Treatment
The investigators will compare the toxicity profiles of the two arms of therapy to determine if the docetaxel + suramin has a more favorable toxicity profile than docetaxel alone. This count includes only adverse events considered definitely, probably, or possibly due to treatment. (NCT01671332)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel | 35 |
| Docetaxel Plus Suramin | 31 |
Evaluation of Peripheral Blood Lymphocytes for DNA Damage-induced Checkpoint Control.
The investigators hypothesize that suramin in combination with docetaxel improves response rates and survival by increasing the cancer cell population in the M phase of the cell cycle. The G2-M checkpoint control score, defined as (%M-phase arrested cells after cisplatin+suramin)/(%M-phase arrested cells after cisplatin), is an indicator of the effect of suramin on cell accumulation in the M-phase. G2-M checkpoint control was evaluated as a predictor of PFS and OS in participant receiving suramin by linear correlation. (NCT01671332)
Timeframe: Baseline
| Intervention | G2-M checkpoint control score (Mean) |
|---|
| Docetaxel | 0.91 |
| Docetaxel Plus Suramin | 1.30 |
Progression-free Survival in Months
Compare progression-free survival (PFS) in participants with advanced NSCLC treated with docetaxel with or without suramin after failure of first-line chemotherapy. PFS is defined as the duration of time from the time of randomization to time of disease progression or death, whichever occurs first. (NCT01671332)
Timeframe: Up to 1 year
| Intervention | months (Median) |
|---|
| Docetaxel | 2.8 |
| Docetaxel Plus Suramin | 1.6 |
Response Rate Per RECIST 1.1 Criteria
"Response rate per RECIST 1.1, as follows:~Complete response (CR): Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to <10 mm in short axis Partial response (PR): At least 30% decrease in the sum of longest diameters (SLD) of target lesions, taking as reference the baseline sum diameters Progressive disease (PD): SLD increased by at least 20% from the smallest value on study (including baseline, if that is smallest). The SLD must also demonstrate an absolute increase of at least 5 mm. (Two lesions increasing from 2mm to 3mm, for example, does not qualify).~Stable disease (SD): Neither sufficient shrinkage to qualify for PR not sufficient increase to qualify for PD" (NCT01671332)
Timeframe: Up to 1 year
| Intervention | participants (Number) |
|---|
| Partial Response | Stable Disease | Progressive Disease | Not Assessed |
|---|
| Docetaxel | 1 | 17 | 17 | 5 |
,| Docetaxel Plus Suramin | 3 | 11 | 25 | 1 |
Objective Response Rate (ORR) by PD-L1 Expression at Baseline
ORR was defined as the percentage of all randomized participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). 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. CR+PR, confidence interval based on the Clopper and Pearson method. ORR was reported for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. (NCT01673867)
Timeframe: From randomization to date of objectively documented progression (up to approximately 110 months)
| Intervention | Percentage of participants (Number) |
|---|
| Participants with baseline PD-L1 expression ≥ 5% | Participants with baseline PD-L1 expression < 5% |
|---|
| Docetaxel | 12.8 | 14.5 |
,| Nivolumab | 36.2 | 10.9 |
Duration of Objective Response (DOOR)
DOR was defined as the time from the date of first confirmed response to the date of the first documented tumor progression (per RECIST v1.1), as determined by the investigator, or death due to any cause, whichever occurred first. DOR was evaluated only for confirmed responders (i.e. participants with confirmed CR or PR). 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. Participants who neither progressed nor died were censored on the date of their last evaluable tumor assessment. Median computed using Kaplan-Meier method. (NCT01673867)
Timeframe: From randomization to date of first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 110 months)
| Intervention | Months (Median) |
|---|
| Nivolumab | 17.15 |
| Docetaxel | 5.55 |
Overall Survival (OS) - Extended Collection
Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. OS will be followed continuously while participants are on the study drug and every 3 months via in-person or phone contact after participants discontinue the study drug. Median computed using Kaplan-Meier method. Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until December 17, 2021). (NCT01673867)
Timeframe: From randomization to the date of death or last known date alive (up to approximately 110 months)
| Intervention | Months (Median) |
|---|
| Nivolumab | 12.21 |
| Docetaxel | 9.49 |
Overall Survival (OS) Time in Months for All Randomized Participants at Primary Endpoint
Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. OS will be followed continuously while participants are on the study drug and every 3 months via in-person or phone contact after participants discontinue the study drug. Median and hazard ratio computed using Kaplan-Meier method. (NCT01673867)
Timeframe: Randomization until 413 deaths, up to March 2015 (approximately 29 months)
| Intervention | Months (Median) |
|---|
| Nivolumab | 12.19 |
| Docetaxel | 9.36 |
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to the date of the first documented tumor progression (per RECIST 1.1) or death due to any cause. Participants who died without a reported prior progression were considered to have progressed on the date of their death. Progression will be assessed every 6 weeks (from the first on-study radiographic assessment) until disease progression is noted. Progressive disease was defined as 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. The appearance of one or more new lesions is also considered progression. Median computed using the Kaplan-Meier method. (NCT01673867)
Timeframe: From randomization to first confirmed response to the date of the first documented tumor progression or death due to any cause, whichever occurred first (up to approximately 110 months)
| Intervention | Months (Median) |
|---|
| Nivolumab | 2.33 |
| Docetaxel | 4.44 |
Overall Survival (OS) by PD-L1 Expression at Baseline
Overall survival was defined as the time from randomization to the date of death. A participant who has not died will be censored at last known date alive. Overall Survival time was measured in months for all randomized participants grouped by their baseline PD-L1 expression level. PD-L1 expression in participants was defined as the percent of disease tumor cells demonstrating plasma membrane PD-L1 staining of any intensity using an immunohistochemistry (IHC) assay. Median computed using the Kaplan-Meier method. (NCT01673867)
Timeframe: From randomization to the date of death or last known date alive (up to approximately 110 months)
| Intervention | Months (Median) |
|---|
| Participants with baseline PD-L1 expression ≥ 5% | Participants with baseline PD-L1 expression < 5% |
|---|
| Docetaxel | 8.11 | 10.28 |
,| Nivolumab | 19.91 | 9.86 |
Time To Objective Response (TTOR)
Time to Objective Response for participants demonstrating a response (either CR or PR) was defined as the time from the date of randomization to the date of the first confirmed 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.; PR = At least a 30% decrease in the sum of diameters of target lesions, taking, as reference, the baseline sum diameters. (NCT01673867)
Timeframe: From randomization to the date of first confirmed response (up to approximately 110 months)
| Intervention | Months (Median) |
|---|
| Nivolumab | 2.10 |
| Docetaxel | 2.73 |
Objective Response Rate (ORR)
ORR was defined as the percentage of participants whose Best Overall Response (BOR) was a confirmed Complete Response (CR) or Partial Response (PR). BOR was defined as the best investigator-assessed response designation, recorded between the date of randomization and the date of objectively documented progression per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) or the date of subsequent anti-cancer therapy (excluding on-treatment palliative radiotherapy of non-target bone lesions or Central Nervous System (CNS) lesions), whichever occurred first. 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. CR+PR, confidence interval based on the Clopper and Pearson method. (NCT01673867)
Timeframe: From randomization to date of objectively documented progression (up to approximately 110 months)
| Intervention | Percentage of participants (Number) |
|---|
| Nivolumab | 19.5 |
| Docetaxel | 12.8 |
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0)
Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in 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. (NCT01683994)
Timeframe: Adverse events were assessed from the date treatment consent signed to date off study, approximately 45 months and 14 days for Arm A; 43 months and 14 days for Arm B; 9 months and 11 days for DL1; 27 months and 1 day for DL2; & 11 months & 25 days for DL3
| Intervention | Participants (Count of Participants) |
|---|
| Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | 4 |
| Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | 8 |
| Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | 7 |
| Ph II Arm A: Docetaxel + Prednisone | 12 |
| Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | 13 |
Progression Free Survival (PFS) of Cabozantinib + Docetaxel + Prednisone Compared to Docetaxel + Prednisone Alone
PFS is the time interval from start of treatment to documented evidence of disease progression or death. Disease progression was assessed by the Response Criteria in Solid Tumors (RECIST) and is defined as at least a 20% increase in the sum of the diameters of target lesions as referenced by the smallest sum on study. Appearance of one or more new lesions on bone scan and/or two consecutive rising prostatic-specific antigen values above the baseline at a minimum of one week intervals. A normal PSA value is 4.0 ng/ml and lower. (NCT01683994)
Timeframe: From start date of treatment until the date of first documented progression, date of death from any cause and up to 40 months, whichever occurred first.
| Intervention | months (Median) |
|---|
| Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | 8 |
| Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | 13 |
| Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | 6 |
| Ph II Arm A: Docetaxel + Prednisone | 10 |
| Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | 6.5 |
Number of Participants Achieving Prostatic-Specific Antigen (PSA) Decline of 30% or 50% From Baseline
PSA normal range is 4 ng/ml or lower. Participants with PSA decline of 30% or 50% is the measures for prostate cancer based on conventional reporting metrics. (NCT01683994)
Timeframe: up to 38 months
| Intervention | Participants (Count of Participants) |
|---|
| Decline in PSA>30% from baseline | Decline in PSA>50% from baseline |
|---|
| Ph I Dose Level 1:Cabozantinib + Docetaxel + Prednisone | 0 | 0 |
,| Ph I Dose Level 2:Cabozantinib + Docetaxel + Prednisone | 5 | 5 |
,| Ph I Dose Level 3:Cabozantinib + Docetaxel + Prednisone | 5 | 4 |
,| Ph II Arm A Docetaxel + Prednisone | 5 | 3 |
,| Ph II Arm B: Cabozantinib + Docetaxel + Prednisone | 10 | 9 |
Number of Participants With a Dose Limiting Toxicities (DLTs)
A DLT are defined as adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) occurring during the first two cycles of therapy and related to the study medications (attributions: possible, probable, and definite) while fulfilling one of the following criteria: Any Grade 3 or greater non-hematologic toxicity except asymptomatic grade 3 hypertension, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, and asymptomatic grade 4 uric acid. A treatment delay of > 2 weeks due to an adverse event (delays due to dental procedures are not included). Grade 4 neutropenia (absolute neutrophil count <500/µL lasting > 5 days. Febrile neutropenia. Grade 3 thrombocytopenia lasting for 7 days or more or thrombocytopenia < 50K/µL requiring platelet transfusion for bleeding. (NCT01683994)
Timeframe: First two cycles of treatment (each cycle is 21 days), approximately 42 days.
| Intervention | Participants (Count of Participants) |
|---|
| Neutropenic fever | Palmar plantar erythroderma |
|---|
| Ph I Dose Level 1: Cabozantinib + Docetaxel + Prednisone | 0 | 0 |
,| Ph I Dose Level 2: Cabozantinib + Docetaxel + Prednisone | 0 | 0 |
,| Ph I Dose Level 3: Cabozantinib + Docetaxel + Prednisone | 1 | 1 |
Maximum Tolerated Dose (MTD)
MTD is defined as the dose level at which no more than 1 of 6 patients experiences a dose limiting toxicity (DLT) at the level below that which had two instances of DLT. A DLT are defined as adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0) occurring during the first two cycles of therapy and related to the study medications (attributions: possible, probable, and definite) while fulfilling one of the following criteria: Any Grade 3 or greater non-hematologic toxicity except asymptomatic grade 3 hypertension, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, and asymptomatic grade 4 uric acid. A treatment delay of > 2 weeks due to an adverse event (delays due to dental procedures are not included). Grade 4 neutropenia (absolute neutrophil count <500/µL lasting > 5 days. Febrile neutropenia. Grade 3 thrombocytopenia lasting for 7 days or more or thrombocytopenia < 50K/µL requiring platelet transfusion for bleeding. (NCT01683994)
Timeframe: First two cycles of treatment (each cycle is 21 days), approximately 42 days.
| Intervention | mg (Number) |
|---|
| Ph I Cabozantinib + Docetaxel + Prednisone | 40 |
Overall Survival (OS)
OS was defined as time from baseline 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 participant was known to be alive. (NCT01703091)
Timeframe: Baseline to Death from Any Cause (Up to 28 Months)
| Intervention | Months (Median) |
|---|
| Ramucirumab + Docetaxel | 15.15 |
| Placebo + Docetaxel | 14.65 |
Change From Baseline in Lung Cancer Symptom Scale (LCSS)
The participant-reported LCSS was a 9-item questionnaire. Six items were symptom-specific measures for lung cancer (loss of appetite, fatigue, cough, dyspnea, hemoptysis, and pain), and 3 summation items described total symptomatic distress, interference with activity level, and global quality of life. Participant responses to each item were measured using a visual analog scale (VAS) from 0 (best outcome) to 100 (worst outcome). The Average Symptom Burden Index (ASBI) was the mean of the 6 symptom-specific items in the LCSS. The Total LCSS was the mean of all 9 LCSS items. Maximum improvement in LCSS scores, ASBI, and Total LCSS score was the largest decrease from baseline for each variable, which was the smallest (most negative or smallest positive) non-missing value among all change from baseline values for each variable. (NCT01703091)
Timeframe: Baseline to Measured Progressive Disease or Participant Stopped Study (up to 97 weeks)
| Intervention | Millimeter (Mean) |
|---|
| Loss of Appetite (n=73, 79) | Fatigue (n=73, 80) | Cough (n=73, 80) | Dyspnea (n=73, 80) | Hemoptysis (n=73, 80) | Pain (n=73, 80) | Overall Symptoms (n=73, 80) | Interference with Activity Level (n=73, 80) | Quality of Life (n=73, 80) | ASBI (n=73, 79) | Total LCSS (n=73, 79) |
|---|
| Placebo + Docetaxel | -16.2 | -7.8 | -18.3 | -8.7 | -3.7 | -9.0 | -11.5 | -11.9 | -12.7 | -6.93 | -7.13 |
,| Ramucirumab + Docetaxel | -12.5 | -4.9 | -4.4 | -4.7 | -1.2 | -9.6 | -7.1 | -8.4 | -11.7 | -2.82 | -3.20 |
Change From Baseline in European Quality of Life Questionnaire - 5 Dimension (EQ-5D) Index Score
The EQ-5D is a quality-of-life instrument which allowed participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 3 (no problem, some problems, and extreme problems, respectively). These combinations of attributes were converted into a weighted Health State Index score according to a United Kingdom population-based algorithm; the possible values for the Health State Index score ranged from -0.59 (severe problems in all 5 dimensions) to 1.0 (no problem in any dimension). (NCT01703091)
Timeframe: Baseline, Day 21 Each Cycle (Cycle = 21 Days) and 30-Day Follow Up (Up to 97 Weeks)
| Intervention | Units on a Scale (Mean) |
|---|
| Cycle 1 (n = 69, 77) | Cycle 2 (n = 62, 66) | Cycle 3 (n = 48, 53) | Cycle 4 (n = 40, 48) | Cycle 5 (n = 32, 40) | Cycle 6 (n = 28, 36) | Cycle 7 (n = 25 ,31) | Cycle 8 (n = 23, 30) | 30-Day Follow Up (n= 56, 70) |
|---|
| Placebo + Docetaxel | -0.007 | 0.006 | -0.005 | -0.026 | -0.012 | -0.005 | -0.039 | -0.071 | -0.132 |
,| Ramucirumab + Docetaxel | -0.024 | -0.021 | -0.010 | 0.015 | 0.000 | 0.035 | 0.002 | -0.053 | -0.102 |
Progression-Free Survival (PFS)
PFS was defined as the time from baseline until measured progressive disease (PD) or death from any cause, whichever is first. According to Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1), PD was 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 20% relative increase, the sum must have also demonstrated an absolute increase of at least 5 millimeters (mm). The appearance of 1 or more new lesions and/or unequivocal progression of existing nontarget lesions was also considered progression. Participants without objectively determined PD, who were alive at the end of the follow-up period (or lost to follow-up), were censored on the date of the participant's last complete radiographic tumor assessment; if no baseline or post-baseline radiologic assessment was available, the participant was censored at the date of randomization. (NCT01703091)
Timeframe: Baseline to Measured Progressive Disease or Death from Any Cause (Up to 21 Months)
| Intervention | Months (Median) |
|---|
| Ramucirumab + Docetaxel | 5.22 |
| Placebo + Docetaxel | 4.21 |
Percentage of Participants Who Achieved Best Overall Tumor Response of Complete Response (CR) or Partial Response (PR) [Objective Tumor Response Rate (ORR)]
Participants achieved an objective response if they had a best overall response of complete response (CR) or partial response (PR). According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal [ULN]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. The percentage of participants who achieved an objective response equals (number of participants with CR or PR)/(number of participants assessed)*100. (NCT01703091)
Timeframe: Baseline to Measured Progressive Disease or Participant Stops Study (Up to 97 Weeks)
| Intervention | Percentage of Participants (Number) |
|---|
| Ramucirumab + Docetaxel | 28.9 |
| Placebo + Docetaxel | 18.5 |
Percentage of Participants Who Achieved Best Overall Disease Response of CR, PR or Stable Disease (SD) [Disease Control Rate (DCR)]
Participants achieved disease control if they had a best overall response of PR, CR or SD. According to RECIST v1.1, CR was the disappearance of all non-nodal target lesions, with the short axes of any target lymph node reduced to <10 mm, the disappearance of all nontarget lesions, and the normalization of tumor marker levels (if tumor markers were initially above the upper limit of normal [ULN]); PR was defined as at least a 30% decrease in the sum of the diameters of target lesions (including the short axes of any target lymph node), taking as reference the baseline sum diameter. SD was neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD, taking as reference the smallest sum diameter since treatment started. The percentage of participants who achieved disease control equals (number of participants with CR, PR, or SD)/(number of participants assessed)*100. (NCT01703091)
Timeframe: Baseline to Measured Progressive Disease or Participant Stopped Study (Up to 97 Weeks)
| Intervention | Percentage of Participants (Number) |
|---|
| Ramucirumab + Docetaxel | 78.9 |
| Placebo + Docetaxel | 70.4 |
Overall Survival
Number of participants alive at 2 years. (NCT01715233)
Timeframe: 2 Years
| Intervention | Participants (Count of Participants) |
|---|
| Metastatic Esophageal, Gastroesophageal And Gastric Cancer. | 2 |
CHFR Methylation Status
Number of participants with advanced esophagogastric cancer that are CHFR-methylated or unmethylated at baseline. (NCT01715233)
Timeframe: Baseline
| Intervention | Participants (Count of Participants) |
|---|
| CHFR-methylated | CHFR-unmethylated |
|---|
| Metastatic Esophageal, Gastroesophageal & Gastric Cancer. | 6 | 12 |
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
| Intervention | Participants (Count of Participants) |
|---|
| CHFR-methylated72174376 | CHFR-unmethylated72174376 | Unknown methylation status72174376 |
|---|
| SD | non-CR/non-PD | PR/PD | PR | PD |
|---|
| 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 |
PSA Progression Free Survival
PSA progression-free survival before any switch and PSA progression free survival during the study was defined as the time interval between the date of Day 1 of Cycle 1 to the date of either first PSA progression or death due to any cause whichever came first. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/mL] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart). (NCT01718353)
Timeframe: From Baseline until DP or death due to any cause or study cut off date, whichever was earlier (Maximum duration: 60 weeks)
| Intervention | months (Median) |
|---|
| Before switch | whole treatment continuum |
|---|
| Overall Population (Treatment A or Treatment B) | NA | 12.4 |
Radiographic Progression-free Survival (rPFS)
(NCT01718353)
Timeframe: From baseline, every 12 weeks until radiological tumor progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)
| Intervention | months (Median) |
|---|
| Overall Population (Treatment A or Treatment B) | NA |
Progression Free Survival (PFS)
PFS was defined as the time interval between the date of random allocation of the treatment and the date of first documentation of any of the following: radiographic tumor progression (using Modified Response Evaluation Criteria in Solid Tumors [RECIST1.1] before any switch and during the study), clinical progression (including skeletal-related events, increasing pain requiring escalation of narcotic analgesics, urinary obstruction), PSA progression or death from any cause. Analysis was performed by Kaplan Meier method. (NCT01718353)
Timeframe: From Baseline until DP or death due to any cause or study cut off, whichever was earlier (Maximum duration: 60 weeks)
| Intervention | months (Median) |
|---|
| Before switch | Whole treatment continuum |
|---|
| Overall Population (Treatment A or Treatment B) | 4.1 | 9.1 |
Percentage of Participants With PSA Response
PSA response was defined as ≥50% decrease in PSA levels in both treatment arms from baseline, during the whole treatment, before treatment switch and after treatment switch. PSA progression was defined as decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the nadir value, confirmed by a second PSA value at least 3 weeks apart) and no decline of PSA from baseline (an increase of ≥25% [at least 2ng/ml] over the baseline value after 12 weeks of treatment, confirmed by a second PSA value at least 3 weeks apart). Because the purpose of this study is to explore the benefit of a regimen in which participants are switched to a different taxane if PSA does not decrease ≥30% after 4 cycles, irrespective of which agent (docetaxel or cabazitaxel) is administered initially, the data for participants who began treatment with docetaxel and for those who began treatment with cabazitaxel were combined for the efficacy analyses. (NCT01718353)
Timeframe: Baseline, Pre-dose every 3 weeks, 30 days after last treatment administration (End of treatment [EOT]), every 3 months (for 1 year) then every 6 months until PSA progression or study cut-off, whichever was earlier (Maximum duration: 60 weeks)
| Intervention | percentage of participants (Number) |
|---|
| PSA response before switch | PSA response after switch | Overall PSA response |
|---|
| Overall Population (Treatment A or Treatment B) | 39.7 | 15.9 | 55.6 |
Percentage of Participants With ≥30% and ≥50% Reduction in PSA Response
Participants with ≥30% and ≥50% reduction in PSA response from base line were evaluated in participants who were previously treated with a high potency androgen receptor (AR)-targeted agent (AR signaling inhibitor or cytochrome P450 17 alphahydroxylase/17,20lyase [CYP 17] inhibitor). (NCT01718353)
Timeframe: From baseline until DP or study cut-off, whichever was earlier (Maximum duration: 60 weeks)
| Intervention | percentage of participants (Number) |
|---|
| ≥30% reduction | ≥50% reduction |
|---|
| Overall Population (AR-target Agent Treated) | 52.0 | 44.0 |
,| Overall Population (Non AR-target Agent Treated) | 74.3 | 68.6 |
Clinical Progression-free Survival (cPFS)
cPFS was assessed before switch and during the study including skeletal-related events (SRE), increasing pain requiring escalation of narcotic analgesics, urinary obstruction, etc. SRE included pathological fractures and/or spinal cord compression, need for bone irradiation (including radioisotopes or bone surgery), change of antineoplastic therapy (including introduction of bisphosphonates or denosumab in the face of increase in pain) to treat bone pain. Pain was assessed using present pain intensity (PPI) scale (0=no pain, up to 5=excruciating pain) and analgesics used for cancer pain (1 point for non-narcotic medications and 4 points for narcotic medications). (NCT01718353)
Timeframe: Baseline, Pre-dose every 3 weeks, EOT, every 3 months (for 1 year) until first SRE occurrence or death or study cut-off, whichever was earlier (Maximum duration: 60 weeks)
| Intervention | months (Median) |
|---|
| Before switch | Whole treatment continuum |
|---|
| Overall Population (Treatment A or Treatment B) | NA | NA |
Overall Survival
Overall survival before switch and overall survival during the study was defined as the time interval from the date of random allocation to the date of death due to any cause until study cut-off date. (NCT01718353)
Timeframe: From baseline until death due to any cause or study cut-off, whichever was earlier (Maximum duration: 60 weeks)
| Intervention | Months (Median) |
|---|
| Before switch | whole treatment continuum |
|---|
| Overall Population (Treatment A or Treatment B) | 8.8 | NA |
Drug-target Engagement in CTCs: Change From Baseline at Cycle 1 Day 8 in MTB by Categories of PSA Decrease From Baseline (≥30%, Not ≥30%) After Cycle 4
Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained AR nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced MTB. Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. MTB in images of CTCs captured by GEDI was qualitatively assessed by three independent operators for increase compared with baseline on a scale of 0 to 3 from no to most MTB increase. Increase from baseline in MTB may indicate inhibition of AR signaling. Change from baseline in MTB at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥30%, Not ≥30%) after Cycle 4. (NCT01718353)
Timeframe: Baseline and Cycle 1 Day 8, Cycle 4
| Intervention | units on a scale (Mean) |
|---|
| PSA decreased ≥30% at Cycle 4 | PSA not decreased ≥30% at Cycle 4 |
|---|
| Overall Population (Treatment A or Treatment B) | 0.69 | 0.09 |
Drug-target Engagement in Circulating Tumor Cells (CTCs): Change From Baseline at Cycle 1 Day 8 in Percent Androgen Receptor Nuclear Localization (%ARNL) by Categories of PSA Decrease From Baseline (≥50%, Not ≥50%) After Cycle 4
Analysis of CTCs is a co-primary endpoint. Growth of prostate cancer cells is dependent on sustained androgen receptor (AR) nuclear signaling. Taxanes (e.g., docetaxel and cabazitaxel) may mediate some of their activity in prostate cancer by impairing AR trafficking along the microtubules from the tumor cell cytoplasm into the nucleus, as a result of taxane-induced microtubule bundling (MTB). Blood samples were collected at baseline and post-treatment to allow isolation of CTCs, which were evaluated for tumor cell biomarker measures %ARNL and MTB score. %ARNL was assessed by quantitative analysis of images of CTCs captured by geometrically enhanced differential immunocapture (GEDI). Reduction from baseline in %ARNL (percentage of total cellular AR that is located in the nucleus) may indicate inhibition of AR signaling. Change from baseline in %ARNL at Cycle 1 Day 8 is summarized by categories of participants with PSA decrease from baseline (≥50%, Not ≥50%) after Cycle 4. (NCT01718353)
Timeframe: Baseline and Cycle 1 Day 8, Cycle 4
| Intervention | percentage ARNL (Mean) |
|---|
| PSA decreased ≥50% at Cycle 4 | PSA not decreased ≥50% at Cycle 4 |
|---|
| Overall Population (Treatment A or Treatment B) | -17.58 | 2.30 |
Absolute ANC Nadir Overtime in Cycle 2
Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2. (NCT01724866)
Timeframe: Cycle 2 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 2.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 3.9 |
| Arm 3: SPI-2012 270 µg/kg and TC | 6.8 |
| Arm 4: Pegfilgrastim and TC | 3.3 |
Depth of ANC Nadir in Cycle 4
Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4. (NCT01724866)
Timeframe: Cycle 4 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 8.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 4.2 |
| Arm 3: SPI-2012 270 µg/kg and TC | 4.2 |
| Arm 4: Pegfilgrastim and TC | 2.4 |
Duration of DSN in Cycle 3
DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 3. (NCT01724866)
Timeframe: Cycle 3 (each cycle was 21 days)
| Intervention | days (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 0.45 |
| Arm 2: SPI-2012 135 µg/kg and TC | 0.16 |
| Arm 3: SPI-2012 270 µg/kg and TC | 0.15 |
| Arm 4: Pegfilgrastim and TC | 0.14 |
Depth of ANC Nadir in Cycle 3
Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3. (NCT01724866)
Timeframe: Cycle 3 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 1.9 |
| Arm 2: SPI-2012 135 µg/kg and TC | 3.4 |
| Arm 3: SPI-2012 270 µg/kg and TC | 4.1 |
| Arm 4: Pegfilgrastim and TC | 3.5 |
Depth of ANC Nadir in Cycle 2
Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 2. (NCT01724866)
Timeframe: Cycle 2 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 1.3 |
| Arm 2: SPI-2012 135 µg/kg and TC | 3.3 |
| Arm 3: SPI-2012 270 µg/kg and TC | 4.8 |
| Arm 4: Pegfilgrastim and TC | 2.9 |
Depth of ANC Nadir in Cycle 1
Depth of ANC nadir was defined as the lowest Median ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1. (NCT01724866)
Timeframe: Cycle 1 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 0.8 |
| Arm 2: SPI-2012 135 µg/kg and TC | 3.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 6.2 |
| Arm 4: Pegfilgrastim and TC | 3.0 |
Time to ANC Recovery in Cycle 4
Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 4. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 4. (NCT01724866)
Timeframe: Cycle 4 (each cycle was 21 days)
| Intervention | days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 11.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 10.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 10.0 |
| Arm 4: Pegfilgrastim and TC | 10.0 |
Area Under the Serum Concentration-Time Curve From Time Zero to 312 Hours Post-Dose (AUC0-312)
AUC(0-312) is the area under the serum concentration-time curve from time zero to 312 hour post dose calculated by the linear trapezoidal rule. Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters. (NCT01724866)
Timeframe: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
| Intervention | nanogram*hour per milliliter (ng*hr/mL) (Mean) |
|---|
| Arm 2: SPI-2012 135 µg/kg and TC | 16000 |
| Arm 3: SPI-2012 270 µg/kg and TC | 22900 |
Absolute Neutrophil Count (ANC) Nadir Overtime in Cycle 1
Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 1. (NCT01724866)
Timeframe: Cycle 1 (each cycle was 21 days)
| Intervention | 10^9 ANC per liter (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 1.5 |
| Arm 2: SPI-2012 135 µg/kg and TC | 4.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 7.2 |
| Arm 4: Pegfilgrastim and TC | 3.2 |
Absolute ANC Nadir Overtime in Cycle 4
Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 4. (NCT01724866)
Timeframe: Cycle 4 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 2.1 |
| Arm 2: SPI-2012 135 µg/kg and TC | 4.1 |
| Arm 3: SPI-2012 270 µg/kg and TC | 4.8 |
| Arm 4: Pegfilgrastim and TC | 2.7 |
Duration of Severe Neutropenia (DSN) in Cycle 1
DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 1. (NCT01724866)
Timeframe: Cycle 1 (each cycle was 21 days)
| Intervention | days (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 1.03 |
| Arm 2: SPI-2012 135 µg/kg and TC | 0.44 |
| Arm 3: SPI-2012 270 µg/kg and TC | 0.03 |
| Arm 4: Pegfilgrastim and TC | 0.31 |
Number of Participants With Worst Grade Adverse Events (AEs), Deaths, Other Serious Adverse Events (SAEs), and Other AEs Leading to Discontinuation From Study Therapy, and Worst Grade Laboratory Abnormalities
"An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. An 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 or incapacity, congenital anomaly. Participants with SAE other than death were reported.AE and Laboratory Abnormalities (Hematology and Chemistry) were collected and graded as per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03, where Grade 3 refers to severe or medically significant but not immediately life threatening; hospitalization or prolongation of hospitalization indicated and Grade 4 refers to life-threatening consequences; urgent intervention indicated." (NCT01724866)
Timeframe: From the first dose up to 30 days post last dose of study drug (up to 4 months)
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3-4 TEAEs | Death | SAEs Other Than Death | TEAEs Leading to Discontinuation From Study Therapy | Grade 3-4 Lab Abnormalities: Hematology | Grade 3-4 Lab Abnormalities: Chemistry |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 24 | 0 | 5 | 0 | 33 | 8 |
,| Arm 2: SPI-2012 135 µg/kg and TC | 12 | 0 | 4 | 2 | 19 | 4 |
,| Arm 3: SPI-2012 270 µg/kg and TC | 13 | 0 | 2 | 1 | 18 | 6 |
,| Arm 4: Pegfilgrastim and TC | 12 | 0 | 8 | 1 | 28 | 8 |
Time to Reach Maximum Concentration of SPI-2012 (Tmax)
Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive pharmacokinetic (PK) parameters. (NCT01724866)
Timeframe: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
| Intervention | hours (hrs) (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 58.7 |
| Arm 2: SPI-2012 135 µg/kg and TC | 9.00 |
| Arm 3: SPI-2012 270 µg/kg and TC | 24.0 |
Time to ANC Recovery in Cycle 3
Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 3. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 3. (NCT01724866)
Timeframe: Cycle 3 (each cycle was 21 days)
| Intervention | days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 10.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 9.5 |
| Arm 3: SPI-2012 270 µg/kg and TC | 9.0 |
| Arm 4: Pegfilgrastim and TC | 10.0 |
Time to ANC Recovery in Cycle 2
Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥2×10^9/L after the expected nadir within Cycle 2. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 2. (NCT01724866)
Timeframe: Cycle 2 (each cycle was 21 days)
| Intervention | days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 11.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 9.5 |
| Arm 3: SPI-2012 270 µg/kg and TC | 10.0 |
| Arm 4: Pegfilgrastim and TC | 10.0 |
Time to ANC Recovery in Cycle 1
Time to ANC recovery was defined as the time from chemotherapy administration until ANC increased to ≥ 2×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was not calculated for participants whose ANC value didn't drop below 2 x10^9/L within Cycle 1. (NCT01724866)
Timeframe: Cycle 1 (each cycle was 21 days)
| Intervention | days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 10.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 8.5 |
| Arm 3: SPI-2012 270 µg/kg and TC | 8.0 |
| Arm 4: Pegfilgrastim and TC | 9.0 |
Time to ANC Nadir in Cycle 1
Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir. (NCT01724866)
Timeframe: Cycle 1 (each cycle was 21 days)
| Intervention | Days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 8.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 7.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 7.0 |
| Arm 4: Pegfilgrastim and TC | 7.5 |
Time to ANC Nadir in Cycle 4
Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir. (NCT01724866)
Timeframe: Cycle 4 (each cycle was 21 days)
| Intervention | days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 8.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 8.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 8.0 |
| Arm 4: Pegfilgrastim and TC | 8.0 |
Duration of DSN in Cycle 4
DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 4. (NCT01724866)
Timeframe: Cycle 4 (each cycle was 21 days)
| Intervention | days (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 1.05 |
| Arm 2: SPI-2012 135 µg/kg and TC | 0.19 |
| Arm 3: SPI-2012 270 µg/kg and TC | 0.09 |
| Arm 4: Pegfilgrastim and TC | 0.11 |
Time to ANC Nadir in Cycle 3
Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir. (NCT01724866)
Timeframe: Cycle 3 (each cycle was 21 days)
| Intervention | days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 8.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 7.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 8.0 |
| Arm 4: Pegfilgrastim and TC | 8.0 |
Percentage of Participants With Hospitalization Across All Cycles From Cycle 1 to Cycle 4
(NCT01724866)
Timeframe: All cycles from Cycle 1 to Cycle 4 (each cycle was 21 days)
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 7.7 |
| Arm 2: SPI-2012 135 µg/kg and TC | 8.3 |
| Arm 3: SPI-2012 270 µg/kg and TC | 2.8 |
| Arm 4: Pegfilgrastim and TC | 13.9 |
Time to ANC Nadir in Cycle 2
Time to ANC nadir was defined as the time from chemotherapy administration until the occurrence of the ANC nadir. (NCT01724866)
Timeframe: Cycle 2 (each cycle was 21 days)
| Intervention | days (Median) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 8.0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 7.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 8.0 |
| Arm 4: Pegfilgrastim and TC | 8.0 |
Percentage of Participants With Febrile Neutropenia (FN) Across All Cycles From Cycle 1 to Cycle 4
FN was defined as a temperature of more than 38.2 degree Celsius (°C) concurrent with an ANC greater than 0.5×10^9/L.. (NCT01724866)
Timeframe: Cycle 1 to Cycle 4 (each cycle was 21 days)
| Intervention | percentage of participants (Number) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 7.7 |
| Arm 2: SPI-2012 135 µg/kg and TC | 2.8 |
| Arm 3: SPI-2012 270 µg/kg and TC | 2.8 |
| Arm 4: Pegfilgrastim and TC | 5.6 |
Maximum Concentration of SPI-2012 (Cmax)
Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters. (NCT01724866)
Timeframe: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
| Intervention | nanograms per milliliter (ng/mL) (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 7.00 |
| Arm 2: SPI-2012 135 µg/kg and TC | 247 |
| Arm 3: SPI-2012 270 µg/kg and TC | 299 |
Number of Participants With Positive Antibodies for SPI-2012
Serum samples were to be tested in a screening assay for antibodies binding to SPI-2012 using a validated enzyme-linked immunosorbent assay (ELISA). Any serum samples positive for the antibody were to be tested in a confirmatory competitive inhibition assay using two antigens, SPI-2012 or granulocyte colony-stimulating factor (G-CSF), to confirm the presence of antibodies binding to SPI-2012 and to identify samples that were positive for antibodies binding to G-CSF. (NCT01724866)
Timeframe: Up to the end of the study (Approximately 3.5 months)
| Intervention | Participants (Count of Participants) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 0 |
| Arm 2: SPI-2012 135 µg/kg and TC | 0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 2 |
Half-life of SPI-2012 (t1/2)
t1/2 data were calculated and reported as harmonic mean and pseudo standard deviation (SD). Blood samples were collected at specific time points to determine the serum concentrations of SPI-2012 and to derive PK parameters. (NCT01724866)
Timeframe: Pre-dose and at 1, 3, 6, 8, 10, 24, 48, 72, 144, 192, and 312 hours post-dose in Cycle 1 (each cycle was 21 days)
| Intervention | hrs (Mean) |
|---|
| Arm 2: SPI-2012 135 µg/kg and TC | 81.0 |
| Arm 3: SPI-2012 270 µg/kg and TC | 31.5 |
Absolute ANC Nadir Overtime in Cycle 3
Mean ANC nadir was defined as the mean of the lowest ANC value (*10^9/L) after administration of the study drug (SPI-2012 or pegfilgrastim) on any day in Days 1-3 of Cycle 3. (NCT01724866)
Timeframe: Cycle 3 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 2.3 |
| Arm 2: SPI-2012 135 µg/kg and TC | 4.4 |
| Arm 3: SPI-2012 270 µg/kg and TC | 6.1 |
| Arm 4: Pegfilgrastim and TC | 3.5 |
Duration of DSN in Cycle 2
DSN was defined as the interval from the day of first observation of severe neutropenia (ANC <0.5*10^9/L, Grade 4 neutropenia per NCI CTCAE) to the first ANC recovery to => 2.0*10^9/L in Cycle 2. (NCT01724866)
Timeframe: Cycle 2 (each cycle was 21 days)
| Intervention | days (Mean) |
|---|
| Arm 1: SPI-2012 45 µg/kg and TC | 0.46 |
| Arm 2: SPI-2012 135 µg/kg and TC | 0.12 |
| Arm 3: SPI-2012 270 µg/kg and TC | 0.03 |
| Arm 4: Pegfilgrastim and TC | 0.08 |
Overall Survival (OS)
The time from randomisation until death due to any cause. Any subject not known to have died at the time of analysis will be censored based on the last recorded date on which the subject was known to be alive (NCT01750281)
Timeframe: Following progression, survival status was collected every 8 weeks until death, withdrawal of consent, or end of study, whichever occurred first, up to 29 months (at the time of the analysis)
| Intervention | Months (Median) |
|---|
| Placebo + Docetaxel 75 mg/m^2 | 11.5 |
| Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | 5.7 |
| Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 | 7.7 |
Progression Free Survival (PFS)
Median time from randomisation 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 (RECIST v1.1): >= 20% increase in the sum of diameters of Target Lesions (TL) and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of Non TLs or a new lesion. (NCT01750281)
Timeframe: Baseline and then every 6 weeks after randomization until objective disease progression, up to 29 months (at the time of the analysis)
| Intervention | Months (Median) |
|---|
| Placebo + Docetaxel 75 mg/m^2 | 4.3 |
| Selumetinib 75 mg BD + Docetaxel 60 mg/m^2 | 3.0 |
| Selumetinib 75 mg BD + Docetaxel 75 mg/m^2 | 4.2 |
Margin-negative (R0) Resection Rate
R0 rate for all participants with resection. Margin negative surgery (R0 resection) is an absolute part of the curative treatment of pancreatic cancer.The primary endpoint is correlation of a radio sensitivity index score derived from the microarray analysis and pathologic response on surgical specimens. Tumor regression Rating: R0 (Complete Response). R0 resections are scored as those resections in which the common bile duct margin, pancreatic resection margin, retroperitoneal margin are negative for tumor involvement. (NCT01754623)
Timeframe: Up to 3 years
| Intervention | percentage of participants (Number) |
|---|
| Chemotherapy Followed by Radiation Treatment | 67 |
Overall Survival (OS) Rate
OS at time of analysis, calculated from date of enrollment to date of death from any cause. (NCT01754623)
Timeframe: 12 months
| Intervention | percentage of participants (Number) |
|---|
| All Participants -Chemotherapy Followed by Radiation Treatment | 33 |
| Resection Group -Chemotherapy Followed by Radiation Treatment | 100 |
Clinical Benefit Rate
The percentage of participants with an overall response (complete or partial remission) or with stable disease. (NCT01777945)
Timeframe: approximately 2 years
| Intervention | percentage of participants (Number) |
|---|
| Participants Receiving Capecitabine/Docetaxel | 73.3 |
Time to Treatment Failure
The time from enrollment to discontinuation of any drug of the treatment combination. (NCT01777945)
Timeframe: approximately 2 years
| Intervention | months (Mean) |
|---|
| Participants Receiving Capecitabine/Docetaxel | 4.64 |
Progression-free Survival (PFS)
The time from enrollment until disease progression, assessed as the time to tumor progression, as evaluated by regular examinations per routine clinical practice, or death from any cause. (NCT01777945)
Timeframe: approximately 2 years
| Intervention | months (Median) |
|---|
| Participants Receiving Capecitabine/Docetaxel | 9.89 |
Percentage of Capecitabine Dose Modifications
(NCT01777945)
Timeframe: approximately 2 years
| Intervention | percentage of doses (Number) |
|---|
| Participants Receiving Capecitabine/Docetaxel | 44.4 |
Duration of Treatment With Xeloda
(NCT01777945)
Timeframe: approximately 2 years
| Intervention | treatment cycle (Mean) |
|---|
| Participants Receiving Capecitabine/Docetaxel | 6.24 |
Overall Response Rate
The percentage of participants with complete or partial remission, based on evaluation of tumor responses assessed at regular examinations per routine clinical practice. (NCT01777945)
Timeframe: approximately 2 years
| Intervention | percentage of participants (Number) |
|---|
| Participants Receiving Capecitabine/Docetaxel | 28.9 |
Number of Participants With Adverse Events
(NCT01777945)
Timeframe: approximately 2 years
| Intervention | participants (Number) |
|---|
| Participants Receiving Capecitabine/Docetaxel | 33 |
Death Rate
(NCT01779050)
Timeframe: Up to 3 years after completion of treatment (estimated to be 4 years)
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Definitive Therapy) | 1 |
| Arm II (Definitive Therapy, Trastuzumab) | 0 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| Arm I (Definitive Therapy) | 1 |
| Arm II (Definitive Therapy, Trastuzumab) | 0 |
Overall Survival
To determine whether docetaxel administered in combination with OGX-427 provides a survival benefit compared to docetaxel alone. (NCT01780545)
Timeframe: 36 Months
| Intervention | months (Median) |
|---|
| Experimental Arm: Arm A | 6.4 |
| Control Arm: Arm B | 5.9 |
Overall Survival (OS) According to Baseline Serum Hsp27 Level.
A subgroup analysis to determine the median overall survival time based on baseline Hsp27 levels. (NCT01780545)
Timeframe: 36 months
| Intervention | months (Median) |
|---|
| Hsp27 <5.7ng/mL | 9.4 |
| Hsp27 >=5.7ng/mL | 4.7 |
Safety and Toxicity of Regimen
To compare the safety and toxicity of OGX-427 in combination with docetaxel to that of docetaxel alone. A summary of per-patient maxiumy grade adverse events of any type is included in the Outcome Measure. Full adverse event information will be submitted further in the record. (NCT01780545)
Timeframe: 36 Months
| Intervention | Participants (Count of Participants) |
|---|
| Maximum AE Grade: 0 | Maximum AE Grade: 1 | Maximum AE Grade: 2 | Maximum AE Grade: 3 | Maximum AE Grade: 4 | Maximum AE Grade: 5 |
|---|
| Control Arm: Arm B | 2 | 7 | 15 | 41 | 26 | 6 |
,| Experimental Arm: Arm A | 0 | 6 | 11 | 40 | 32 | 5 |
Overall Response Rate (ORR) of Participants
ORR is defined as the rate of study participants achieving complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) criteria. (NCT01794845)
Timeframe: Up to 6 months from End of Treatment, about 9 months
| Intervention | percentage of participants (Number) |
|---|
| Overall Response (CR+PR), 1 month | Overall Response (CR+PR), 6 months | Complete Response (CR), 1 month | Complete Response (CR), 6 months | Partial Response (PR), 1 month | Partial Response (PR), 6 months | Stable Disease (SD), 1 month | Stable Disease (SD), 6 months | Progressive Disease (PD), 1 month | Progressive Disease (PD), 6 months |
|---|
| Erbitux, Taxotere, LD Fractionated RT | 50 | 0 | 0 | 0 | 50 | 0 | 25 | 0 | 25 | 100 |
Objective Response Rate (ORR) as of 19 October 2015
"Percentage of participants whose best overall response, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), was either a complete response (CR) or a partial response (PR).~CR was defined as the disappearance (or normalization) of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters." (NCT01798485)
Timeframe: up to 36 months
| Intervention | percentage of participants (Number) |
|---|
| Ganetespib and Docetaxel | 13.7 |
| Docetaxel | 16.0 |
Kaplan-Meier Estimate of Duration of Response (DOR) as of 19 October 2015
"Only participants who achieved a confirmed response (complete response (CR) or partial response (PR)) were included in the DOR analysis.~CR was defined as the disappearance (or normalization) of all target lesions.~PR was defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters." (NCT01798485)
Timeframe: up to 36 months
| Intervention | months (Median) |
|---|
| Ganetespib and Docetaxel | 5.8 |
| Docetaxel | 5.8 |
Progression Free Survival (PFS) in Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015
"The progression-free interval is the interval from the date of randomization until tumor progression per modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1), clinical progression, or death from any cause in the absence of progressive disease, whichever occurs first. Data represents the investigator's assessment.~Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters 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.~Elevated LDH includes values above the upper limit of normal." (NCT01798485)
Timeframe: up to 36 months
| Intervention | months (Median) |
|---|
| Ganetespib and Docetaxel | 3.0 |
| Docetaxel | 2.8 |
Participants With Treatment-Emergent Adverse Events as of 23 December 2015
"Treatment-emergent adverse events (AEs) were defined as AEs that occurred from the time of first dose through 30 days after the last dose of study medication. The Investigator graded the severity of AEs according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) criteria:~Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death A Serious AE (SAE) is defined as 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 or constitutes an important medical event." (NCT01798485)
Timeframe: up to 36 months
| Intervention | participants (Number) |
|---|
| >=1 AE | >=1 AE with CTCAE grade of 3 or 4 | >=1 SAE | >=1 AE leading to dose reduction | >=1 AE leading to delayed dose | >=1 AE leading to study drug discontinuation | >=1 SAE leading to study drug discontinuation | >=1 SAE leading to hospitalization | >=1 SAE with outcome of death | >=1 AE with first occurrence during Cycle 1-2 | >=1 AE with first occurrence during Cycle 1-4 | >=1 AE with first occurrence during Cycle 1-6 |
|---|
| Docetaxel | 307 | 184 | 107 | 37 | 55 | 36 | 15 | 87 | 30 | 280 | 299 | 302 |
,| Ganetespib and Docetaxel | 317 | 222 | 139 | 61 | 125 | 31 | 19 | 109 | 40 | 280 | 304 | 312 |
Disease Control Rate (DCR) as of 19 October 2015
"Percentage of participants whose best overall response, as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST 1.1), was either a complete response (CR), a partial response (PR), or stable disease (SD).~CR was defined as the disappearance (or normalization) of all target lesions. PR was defined as at least 30% decrease in the sum of diameters of target lesions taking as reference the baseline sum of diameters.~SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of diameters while on study. For participants with a best response of SD, duration of SD must be for at least 6 weeks or 12 weeks." (NCT01798485)
Timeframe: up to 36 months
| Intervention | percentage of participants (Number) |
|---|
| >=6 weeks | >=12 weeks |
|---|
| Docetaxel | 60.8 | 46.9 |
,| Ganetespib and Docetaxel | 64.9 | 46.0 |
Progression-free Survival (PFS) as of 19 October 2015
"The progression-free interval is the interval from the date of randomization until tumor progression per modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1), clinical progression, or death from any cause in the absence of progressive disease, whichever occurs first. Data represents the investigator's assessment.~Progressive Disease (PD) was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters 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." (NCT01798485)
Timeframe: up to 36 months
| Intervention | months (Median) |
|---|
| Ganetespib and Docetaxel | 4.2 |
| Docetaxel | 4.3 |
Overall Survival as of 19 October 2015
Overall survival (OS) was measured from the date of randomization to the date of death from any cause. (NCT01798485)
Timeframe: up to 36 months
| Intervention | months (Median) |
|---|
| Ganetespib and Docetaxel | 10.9 |
| Docetaxel | 10.5 |
Overall Survival (OS) In Participants With an Elevated Screening Lactate Dehydrogenase (eLDH) as of 19 October 2015
OS was measured from the date of randomization to the date of death from any cause. Elevated LDH includes values above the upper limit of normal. (NCT01798485)
Timeframe: up to 36 months
| Intervention | months (Median) |
|---|
| Ganetespib and Docetaxel | 7.1 |
| Docetaxel | 9.0 |
Maximum Tolerated Dose (MTD) of FGFR Inhibitor AZD4547
A total of 3 dose levels of AZD4547 were planned: 40mg (level 1), 60mg (level 2), and 80mg (level 3) in combination with a standard dose of docetaxel (75mg/m^2). The starting dose level of AZD4547 was 40 mg. This portion of the study used a standard 3+3 design with patients enrolled in cohorts of 3. The plan was to recommend the maximum tolerated dose (MTD) as the dose level to be used in the phase II portion of the study. MTD is defined as the highest dose level at which less than or equal to 1 of 6 subjects experience dose limiting toxicity (DLT). (NCT01824901)
Timeframe: Assessed during cycle 1 (21 days)
| Intervention | mg (Number) |
|---|
| Phase I | NA |
Progression Free Survival (PFS) Blinded Independent Review Committee Per Blinded Independent Review Committee (BIRC)
PFS is defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause. (NCT01828112)
Timeframe: 'from the date of randomization to the date of first radiologically documented disease progression or death due to any cause up to approximately 24 months
| Intervention | Percentage of participants (Median) |
|---|
| Ceritinib | 5.4 |
| Chemotherapy | 1.6 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| TEAE | SAE |
|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | 4 | 1 |
,| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | 18 | 9 |
,| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | 7 | 2 |
,| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 12 | 3 |
,| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 7 | 1 |
,| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | 6 | 3 |
,| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | 10 | 7 |
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])
| Intervention | ng/ml (Mean) |
|---|
| Cycle 1 Day 1: End-dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 3 hours post dose | Cycle 1 Day 1: 7 hours post dose | Cycle 1 Day 1: 20 hours post dose | Cycle 1 Day 5: End-dose | Cycle 1 Day 5: 1.5 hours post dose | Cycle 1 Day 5: 3 hours post dose | Cycle 1 Day 5: 7 hours post dose | Cycle 1 Day 5: 20 hours post dose |
|---|
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | 152.8 | 137.3 | 86.4 | 63.4 | 14.2 | 211.1 | 115.3 | 96.7 | 38.3 | 9.8 |
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])
| Intervention | percentage of participants (Number) |
|---|
| CR | PR |
|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | 0 | 0 |
,| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | 0 | 19 |
,| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | 0 | 0 |
,| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 18 | 36 |
,| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 0 | 40 |
,| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | 0 | 17 |
,| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | 0 | 0 |
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])
| Intervention | ng/ml (Mean) |
|---|
| Cycle 1 Day 1: End-dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 3 hours post dose | Cycle 1 Day 1: 6 hours post dose | Cycle 1 Day 1: 20 hours post dose | Cycle 1 Day 5: End-dose | Cycle 1 Day 5: 1.5 hours post dose | Cycle 1 Day 5: 3 hours post dose | Cycle 1 Day 5: 6 hours post dose | Cycle 1 Day 5: 20 hours post dose |
|---|
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 429.8 | 253.6 | 192.8 | 136.3 | 30.2 | 253.2 | 171.0 | 118.4 | 76.5 | 10.9 |
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])
| Intervention | nanogram per milliliter (ng/ml) (Mean) |
|---|
| Cycle 1 Day 1: End-dose | Cycle 1 Day 1: 1.5 hours post dose | Cycle 1 Day 1: 3 hours post dose | Cycle 1 Day 1: 20 hours post dose |
|---|
| Arm 1: MLN4924 15 mg/m^2 + Docetaxel 75 mg/m^2 | 163.8 | 82.0 | 48.0 | 7.5 |
,| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | 197.1 | 130.6 | 95.8 | 14.6 |
,| Arm 2: MLN4924 15 mg/m^2+Paclitaxel 175mg/m^2+Carboplatin AUC5 | 275.7 | 156.8 | 152.4 | 23.4 |
,| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 257.3 | 192.7 | 138.0 | 34.6 |
,| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 372.7 | 246.7 | 186.9 | 24.4 |
,| Arm 3: MLN4924 25 mg/m^2 + Gemcitabine 1000 mg/m^2 | 222.0 | 160.5 | 103.0 | 14.2 |
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)
| Intervention | months (Mean) |
|---|
| Arm 1: MLN4924 25 mg/m^2 + Docetaxel 75 mg/m^2 | 2.880 |
| Arm 2a: MLN4924 15 mg/m^2 + Carboplatin AUC6 | 2.270 |
| Arm 2:MLN4924 20 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 16.153 |
| Arm 2:MLN4924 25 mg/m^2+Paclitaxel 175 mg/m^2+Carboplatin AUC5 | 7.015 |
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
| Intervention | Participants (Count of Participants) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 1 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 3 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 1 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 2 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 |
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
| Intervention | Participants (Count of Participants) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 2 |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 4 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 2 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 1 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 12 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 1 |
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
| Intervention | Degree 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 A | 0.35 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0.10 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 1.03 |
| 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 C | 0.12 |
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
| Intervention | Beats per minute (bpm) (Mean) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | -0.3 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 3.2 |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 8.0 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 28.0 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 10.5 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0.6 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | -5.0 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2.8 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 24.4 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 1 Day 1, Urine glucose, >1000 | Cycle 1 Day 1, Urine glucose, 2+ | Cycle 1 Day 1, Urine glucose, trace | Cycle 2 Day 1, Urine glucose, trace | Cycle 4 Day 1, Urine glucose, >=1000 | Cycle 4 Day 1, Urine glucose, 4+ | Cycle 1 Day 1, Urine ketones, trace | Cycle 4 Day 1, Urine ketones, trace | Cycle 28, Day 1, Urine ketones, trace | Cycle 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, trace | Cycle 4 Day 1, Occult Blood, trace | Cycle 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, trace | Cycle 2, Day 1, Urine protein, trace | Cycle 2, Day 1, Urine protein, 2+ | Cycle 4, Day 1, Urine protein, trace | Cycle 8, Day 1, Urine protein, trace | Cycle 12, Day 1, Urine protein, trace | Cycle 16, Day 1, Urine protein, trace |
|---|
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
,| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
,| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 2 | 3 | 1 | 0 |
,| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 0 | 1 | 1 | 0 | 1 | 2 | 0 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 2 | 0 | 1 | 1 | 1 | 0 | 0 | 0 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Baso, decrease to low, n=3,3,14,3,3,3,3,22,8 | Baso, normal or no change, n=3,3,14,3,3,3,3,22,8 | Baso, increase to high, n=3,3,14,3,3,3,3,22,8 | Eos, decrease to low, n=3,3,14,3,3,3,3,24,8 | Eos, normal or no change, n=3,3,14,3,3,3,3,24,8 | Eos, increase to high, n=3,3,14,3,3,3,3,24,8 | Mono, decrease to low, n=3,3,14,3,3,3,3,25,8 | Mono, normal or no change, n=3,3,14,3,3,3,3,25,8 | Mono, increase to high, n=3,3,14,3,3,3,3,25,8 | RBC, decrease to low, n=3,3,14,3,3,3,3,25,8 | RBC, normal or no change, n=3,3,14,3,3,3,3,25,8 | RBC, increase to high, n=3,3,14,3,3,3,3,25,8 |
|---|
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 1 | 1 | 1 | 1 | 3 | 0 | 2 | 0 | 3 | 1 | 2 | 1 |
,| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 3 | 0 | 0 | 3 | 0 | 2 | 0 | 3 | 2 | 1 | 0 |
,| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 3 | 0 | 0 | 3 | 0 | 2 | 2 | 0 | 1 | 2 | 0 |
,| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 5 | 13 | 4 | 8 | 14 | 5 | 6 | 12 | 10 | 17 | 9 | 3 |
,| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 3 | 0 | 0 | 3 | 0 | 1 | 0 | 2 | 2 | 1 | 0 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 1 | 9 | 4 | 1 | 11 | 2 | 11 | 4 | 5 | 10 | 4 | 1 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 1 | 6 | 1 | 3 | 5 | 1 | 3 | 3 | 5 | 3 | 4 | 1 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 3 | 0 | 0 | 3 | 0 | 0 | 2 | 1 | 0 | 3 | 0 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 3 | 0 | 0 | 3 | 0 | 3 | 1 | 0 | 3 | 0 | 0 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Non-serious AEs | SAEs |
|---|
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 3 | 3 |
,| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 3 | 3 |
,| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 3 | 0 |
,| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 24 | 5 |
,| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 3 | 1 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 14 | 5 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 8 | 4 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 3 | 2 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 3 | 0 |
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
| Intervention | Months (Median) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 4.1 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | NA |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 5.5 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 4.6 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 9.5 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 5.1 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 4.6 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 7.4 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 4.1 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Abnormal not clinically significant | Abnormal clinically significant |
|---|
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 2 | 0 |
,| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 2 | 0 |
,| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 1 | 0 |
,| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 12 | 3 |
,| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 3 | 0 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 8 | 1 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2 | 3 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 2 | 0 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 0 |
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
| Intervention | Participants (Count of Participants) |
|---|
| D.Bil, decrease to low, n=2,2,8,1,2,2,1,12,6 | D.Bil, normal or no change, n=2,2,8,1,2,2,1,12,6 | D.Bil, increase to high, n=2,2,8,1,2,2,1,12,6 | Cl, decrease to low, n=3,3,14,3,3,3,3,25,8 | Cl, normal or no change, n=3,3,14,3,3,3,3,25,8 | Cl, increase to high, n=3,3,14,3,3,3,3,25,8 | CO2, decrease to low, n=3,3,14,3,3,3,3,25,8 | CO2, normal or no change, n=3,3,14,3,3,3,3,25,8 | CO2, increase to high, n=3,3,14,3,3,3,3,25,8 | Cr CL, decrease to low, n=3,3,9,2,1,3,3,15,4 | Cr CL, normal or no change, n=3,3,9,2,1,3,3,15,4 | Cr CL, increase to high, n=3,3,9,2,1,3,3,15,4 | T4 free, decrease to low, n=0,1,6,0,1,0,2,16,3 | T4 free, normal or no change,=0,1,6,0,1,0,2,16,3 | T4 free, increase to high, n=0,1,6,0,1,0,2,16,3 | T4 total, decrease to low, n=0,0,0,0,0,0,1,4,1 | T4 total, normal or no change, n=0,0,0,0,0,0,1,4,1 | T4 total, increase to high, n=0,0,0,0,0,0,1,4,1 | Total T3, decrease to low, n=0,1,1,0,1,0,1,6,3 | Total T3, normal or no change, n=0,1,1,0,1,0,1,6,3 | Total T3, increase to high, n=0,1,1,0,1,0,1,6,3 | Urea/BUN, decrease to low, n=3,2,13,3,2,3,3,25,8 | Urea/BUN,normal or no change,n=3,2,13,3,2,3,3,25,8 | Urea/BUN, increase to high, n=3,2,13,3,2,3,3,25,8 |
|---|
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 1 | 0 | 2 | 1 | 0 | 1 | 2 | 0 | 1 | 2 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 2 |
,| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 7 | 5 | 9 | 15 | 2 | 2 | 17 | 7 | 9 | 6 | 1 | 1 | 12 | 3 | 1 | 1 | 2 | 3 | 2 | 1 | 4 | 11 | 10 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 5 | 1 | 3 | 5 | 2 | 0 | 5 | 3 | 0 | 4 | 0 | 1 | 2 | 0 | 0 | 0 | 1 | 2 | 1 | 0 | 1 | 3 | 4 |
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
| Intervention | Participants (Count of Participants) |
|---|
| D.Bil, decrease to low, n=2,2,8,1,2,2,1,12,6 | D.Bil, normal or no change, n=2,2,8,1,2,2,1,12,6 | D.Bil, increase to high, n=2,2,8,1,2,2,1,12,6 | Cl, decrease to low, n=3,3,14,3,3,3,3,25,8 | Cl, normal or no change, n=3,3,14,3,3,3,3,25,8 | Cl, increase to high, n=3,3,14,3,3,3,3,25,8 | CO2, decrease to low, n=3,3,14,3,3,3,3,25,8 | CO2, normal or no change, n=3,3,14,3,3,3,3,25,8 | CO2, increase to high, n=3,3,14,3,3,3,3,25,8 | Cr CL, decrease to low, n=3,3,9,2,1,3,3,15,4 | Cr CL, normal or no change, n=3,3,9,2,1,3,3,15,4 | Cr CL, increase to high, n=3,3,9,2,1,3,3,15,4 | T4 free, decrease to low, n=0,1,6,0,1,0,2,16,3 | T4 free, normal or no change,=0,1,6,0,1,0,2,16,3 | T4 free, increase to high, n=0,1,6,0,1,0,2,16,3 | Total T3, decrease to low, n=0,1,1,0,1,0,1,6,3 | Total T3, normal or no change, n=0,1,1,0,1,0,1,6,3 | Total T3, increase to high, n=0,1,1,0,1,0,1,6,3 | Urea/BUN, decrease to low, n=3,2,13,3,2,3,3,25,8 | Urea/BUN,normal or no change,n=3,2,13,3,2,3,3,25,8 | Urea/BUN, increase to high, n=3,2,13,3,2,3,3,25,8 |
|---|
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 2 | 0 | 2 | 1 | 0 | 0 | 3 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 0 |
,| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 1 | 1 | 1 | 0 | 2 | 1 | 1 | 2 | 2 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 0 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 7 | 1 | 5 | 8 | 1 | 3 | 8 | 6 | 1 | 8 | 0 | 1 | 5 | 0 | 0 | 1 | 0 | 0 | 8 | 5 |
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
| Intervention | Participants (Count of Participants) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 1 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 1 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 3 |
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
| Intervention | Participants (Count of Participants) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 1 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 2 |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 6 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 11 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 1 |
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
| Intervention | Participants (Count of Participants) |
|---|
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 14 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 3 |
| 15 mg/kg GSK3052230 + Pemetrexed + Carboplatin: Arm C | 25 |
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
| Intervention | Participants (Count of Participants) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 1 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 3 |
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
| Intervention | Participants (Count of Participants) |
|---|
| D.Bil, decrease to low, n=2,2,8,1,2,2,1,12,6 | D.Bil, normal or no change, n=2,2,8,1,2,2,1,12,6 | D.Bil, increase to high, n=2,2,8,1,2,2,1,12,6 | Cl, decrease to low, n=3,3,14,3,3,3,3,25,8 | Cl, normal or no change, n=3,3,14,3,3,3,3,25,8 | Cl, increase to high, n=3,3,14,3,3,3,3,25,8 | CO2, decrease to low, n=3,3,14,3,3,3,3,25,8 | CO2, normal or no change, n=3,3,14,3,3,3,3,25,8 | CO2, increase to high, n=3,3,14,3,3,3,3,25,8 | Cr CL, decrease to low, n=3,3,9,2,1,3,3,15,4 | Cr CL, normal or no change, n=3,3,9,2,1,3,3,15,4 | Cr CL, increase to high, n=3,3,9,2,1,3,3,15,4 | Urea/BUN, decrease to low, n=3,2,13,3,2,3,3,25,8 | Urea/BUN,normal or no change,n=3,2,13,3,2,3,3,25,8 | Urea/BUN, increase to high, n=3,2,13,3,2,3,3,25,8 |
|---|
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 1 | 1 | 0 | 1 | 2 | 0 | 0 | 1 | 2 | 0 | 3 | 0 | 0 | 2 | 1 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 1 | 0 | 0 | 3 | 0 | 1 | 2 | 0 | 0 | 1 | 1 | 1 | 1 | 1 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 2 | 0 | 1 | 2 | 0 | 0 | 2 | 1 | 1 | 2 | 0 | 1 | 2 | 0 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable disease, discontinued | Stable disease, ongoing | Progressive disease |
|---|
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 0 | 2 | 0 | 0 |
,| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 2 | 1 | 0 | 0 |
,| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 2 | 1 | 0 | 0 |
,| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 11 | 10 | 2 | 1 |
,| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 0 | 2 | 0 | 0 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 6 | 5 | 0 | 2 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0 | 1 | 2 | 0 | 1 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 0 | 2 | 0 | 1 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 1 | 1 | 0 | 1 |
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
| Intervention | Participants (Count of Participants) |
|---|
| No change or any increase | Any Decrease |
|---|
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2 | 3 |
,| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 1 | 1 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 1 | 1 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2 | 0 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 0 | 1 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0 | 1 |
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
| Intervention | Millimeters of mercury (mmHg) (Mean) |
|---|
| DBP, n=3, 2, 9, 3, 2, 2, 3, 21, 5 | SBP, n=3, 1, 13, 2, 2, 2, 3, 21, 4 |
|---|
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 6.0 | 17.5 |
,| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 0.5 | -14.0 |
,| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 2.3 | 3.0 |
,| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 12.8 | 12.5 |
,| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 3.5 | 6.0 |
,| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 2.0 | 9.6 |
,| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 10.6 | 18.7 |
,| 5 mg/kg GSK3052230 + Docetaxel: Arm B | -0.6 | 10.5 |
,| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 6.3 | -12.3 |
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)
| Intervention | Liters (Mean) |
|---|
| Cycle 3,Day 1, n=3, 24, 4 | Cycle 4,Day 1, n=1, 4, 1 | Cycle 5,Day 1, n=1, 23, 3 | Cycle 6,Day 1, n=1, 5, 2 | Cycle 7,Day 1, n=1, 15, 2 |
|---|
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0.303 | -0.340 | 0.240 | 0.310 | 0.530 |
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)
| Intervention | Liters (Mean) |
|---|
| Cycle 3,Day 1, n=3, 24, 4 | Cycle 4,Day 1, n=1, 4, 1 | Cycle 5,Day 1, n=1, 23, 3 | Cycle 6,Day 1, n=1, 5, 2 | Cycle 7,Day 1, n=1, 15, 2 | Cycle 8,Day 1, n=0, 3, 1 | Cycle 9,Day 1, n=0, 15, 1 | Cycle 11,Day 1, n=0, 12, 2 | Cycle 12,Day 1, n=0, 2, 1 | Cycle 13,Day 1, n=0, 8, 2 | Cycle 14,Day 1, n=0, 3, 1 | Cycle 15,Day 1, n=0, 6, 1 | Cycle 17,Day 1, n=0, 4, 1 | Cycle 19,Day 1, n=0, 1, 1 | Cycle 21,Day 1, n=0, 1, 1 | Cycle 23,Day 1, n=0, 1, 1 | Cycle 25,Day 1, n=0, 0, 1 | Cycle 27,Day 1, n=0, 0, 1 | Cycle 31,Day 1, n=0, 0, 1 |
|---|
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0.138 | 0.600 | 0.587 | 0.110 | 0.575 | 0.640 | 1.130 | 0.510 | 0.580 | 0.555 | 0.910 | -0.030 | 0.560 | 0.620 | 0.560 | 0.510 | 0.430 | 0.220 | 0.270 |
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)
| Intervention | Liters (Mean) |
|---|
| Cycle 3,Day 1, n=3, 24, 4 | Cycle 4,Day 1, n=1, 4, 1 | Cycle 5,Day 1, n=1, 23, 3 | Cycle 6,Day 1, n=1, 5, 2 | Cycle 7,Day 1, n=1, 15, 2 | Cycle 8,Day 1, n=0, 3, 1 | Cycle 9,Day 1, n=0, 15, 1 | Cycle 10,Day 1, n=0, 3, 0 | Cycle 11,Day 1, n=0, 12, 2 | Cycle 12,Day 1, n=0, 2, 1 | Cycle 13,Day 1, n=0, 8, 2 | Cycle 14,Day 1, n=0, 3, 1 | Cycle 15,Day 1, n=0, 6, 1 | Cycle 17,Day 1, n=0, 4, 1 | Cycle 19,Day 1, n=0, 1, 1 | Cycle 21,Day 1, n=0, 1, 1 | Cycle 23,Day 1, n=0, 1, 1 |
|---|
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 0.280 | 0.413 | 0.238 | 0.464 | 0.399 | 0.263 | 0.353 | 0.063 | 0.347 | 0.225 | 0.389 | -0.207 | 0.247 | 0.158 | -0.02 | -0.27 | -0.62 |
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
| Intervention | Cycles (Median) |
|---|
| 5 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 7.0 |
| 10 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 15.0 |
| 20 mg/kg GSK3052230 + Paclitaxel + Carboplatin: Arm A | 8.0 |
| 5 mg/kg GSK3052230 + Docetaxel: Arm B | 6.0 |
| 10 mg/kg GSK3052230 + Docetaxel: Arm B | 4.0 |
| 20 mg/kg GSK3052230 + Docetaxel: Arm B | 6.0 |
| 10 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 6.0 |
| 15 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 11.0 |
| 20 mg/kg GSK3052230 + Pemetrexed + Cisplatin: Arm C | 3.0 |
Pathological Response
Pathological response (pCR or microscopic only primary) in both primary and nodes using the Miller-Payne criteria for pathologic response. (NCT01869192)
Timeframe: Up to 8 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm A | 2 |
| Arm B | 8 |
Overall Response Rate
To describe the overall response rate as measured by physical exam and MRI if indicated using the following definition: Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) 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; Overall Response (OR) = CR + PR. (NCT01869192)
Timeframe: Up to 8 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm A | 25 |
| Arm B | 21 |
Ctrough of PF-03084014 in the Expansion Cohort
(NCT01876251)
Timeframe: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | ng/mL (Geometric Mean) |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 89.22 |
Maximum Serum or Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of PF-03084014 in Dose-finding Cohort
Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cmax, C1D2 | Cmax, C1D21 | Ctrough, C1D21 | Cmax, C2D1 | Ctrough, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 744.2 | 677.5 | 170.8 | NA | NA |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 884.8 | 1053 | 214.7 | 885.7 | 186.1 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 896.6 | 1501 | 306.1 | 1100 | 226.4 |
Cmax of PF-03084014 in the Expansion Cohort
(NCT01876251)
Timeframe: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cmax, C1D1 | Cmax, C1D21 |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 496.7 | 982.1 |
Cmax of Docetaxel in Dose-finding Cohort
Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | ng/mL (Geometric Mean) |
|---|
| Cmax, C1D1 | Cmax, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 3447 | NA |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 3711 | 2606 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 2103 | 1965 |
AUClast of PF-03084014 in the Expansion Cohort
(NCT01876251)
Timeframe: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| AUClast, C1D1 | AUClast, C1D21 |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 1098 | 1955 |
AUClast and AUC From Time 0 Extrapolated to Infinite Time (AUCinf) of Docetaxel in Dose-finding Cohort
Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | nanogram (ng)*hour (hr)/milliliter (mL) (Geometric Mean) |
|---|
| AUClast, C1D1 | AUClast, C2D1 | AUCinf, C1D1 | AUCinf, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 4082 | NA | NA | NA |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 3535 | 2377 | NA | 2530 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 2121 | 2136 | 2509 | 2929 |
Area Under the Concentration-time Curve (AUC) From Time 0 to Time of Last Measured Concentration (AUClast) of PF-03084014 in Dose-finding Cohort
Serum PF-03084014 pharmacokinetic (PK) parameters were calculated following twice daily (BID) doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1). (NCT01876251)
Timeframe: Cycle (C) 1 Days (D) 1, 2, 8, and 21; Day 1 of subsequent cycles and at EOT (max reached: Cycle 12)
| Intervention | nanogram (ng)*hour (hr)/milliliter (mL) (Geometric Mean) |
|---|
| C1D2 | C1D21 | C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 1380 | 3234 | NA |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 1779 | 4119 | 1983 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 1839 | 5575 | 2652 |
Progression-free Survival (PFS) at 6 Months - Expansion Cohort
The period from study entry until disease progression, death or date of last contact. Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. (NCT01876251)
Timeframe: Baseline till 6 months post-dose
| Intervention | months (Median) |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 4.1 |
Percentage of Participants With Objective Response (OR)
OR was based on assessment of 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 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 less than [<] 10 millimeters [mm]). No new lesions. PR was defined as more than or equal to (>=) 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. (NCT01876251)
Timeframe: Baseline, every 6 weeks from Cycle 2 onwards up to 26 months
| Intervention | percentage of participants (Number) |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 13.3 |
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 0 |
| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 18.2 |
Number of Participants With Laboratory Abnormalities
Number of participants with laboratory test abnormalities without regard to baseline abnormality. Laboratory test parameters included hematology, coagulation, liver function, renal function, electrolytes, clinical chemistry, and urinalysis (dipstick). (NCT01876251)
Timeframe: Baseline up to 28-35 days after treatment discontinuation (up to Day 280)
| Intervention | participants (Number) |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 15 |
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 3 |
| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 11 |
Number of Participants With Dose-limiting Toxicities (DLTs) in Cycle 1
Any DLT event in Cycle 1: Grade 4 neutropenia lasting more than (>)7 days; febrile neutropenia (Grade more than or equal to [>=] 3 and body temperature >=38.5 degrees Celsius); Grade >=3 neutropenic infection; Grade >=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia without bleeding; Grade >=3 toxicities (except those that had not been maximally treated); Grade 3 prolongation of time from electrocardiogram (ECG) Q wave to the end of the T wave corresponding to electrical systole (QT) corrected for heart rate (QTc) which persisted after correction of reversible causes; delay of 2 weeks in receiving next scheduled cycle due to persisting treatment-related toxicities; and failure to deliver at least 80% of planned dose during first cycle due to treatment-related toxicities. (NCT01876251)
Timeframe: Cycle 1 Days 1-21
| Intervention | participants (Number) |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 1 |
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 1 |
| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 4 |
Duration of Response (DR)
Duration of response (DR) defined as time from start of first documented objective tumor response [Complete Response (CR) or Partial Response (PR)] to first documented objective tumor progression or death due to any cause, whichever occurs first. DR = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7.02. CR: disappearance of all target lesions. PR: at least 30% decrease in the sum of diameters of target lesions. (NCT01876251)
Timeframe: Baseline up to 28-35 days after treatment discontinuation (up to Day 280)
| Intervention | months (Number) |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | NA |
| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | NA |
Volume of Distribution (Vss) of Docetaxel in Dose-finding Cohort
Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | L (Geometric Mean) |
|---|
| Vss, C1D1 | Vss, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | NA | NA |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | NA | 57.37 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 97.34 | 231.5 |
Tmax of PF-03084014 in the Expansion Cohort
(NCT01876251)
Timeframe: C1D1, C1D21, and Day 1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | hr (Median) |
|---|
| Tmax, C1D1 | Tmax, C1D21 |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 0.983 | 1.00 |
Tmax of Docetaxel in Dose-finding Cohort
Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | hr (Median) |
|---|
| Tmax, C1D1 | Tmax, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 0.917 | 0.767 |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 1.00 | 1.00 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 0.983 | 1.00 |
Time to Cmax (Tmax) of PF-03084014 in Dose-finding Cohort
Serum PF-03084014 PK parameters were calculated following BID doses of PF-03084014 given alone (Cycle 1 Day 21) and in combination with docetaxel (Cycle 1 Day 2 and Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | hr (Median) |
|---|
| Tmax, C1D2 | Tmax, C1D21 | Tmax, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 1.02 | 1.00 | 1.03 |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 1.00 | 0.533 | 0.883 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 1.00 | 0.767 | 0.992 |
Terminal Half-life (t1/2) of Docetaxel in Dose-finding Cohort
Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | hr (Mean) |
|---|
| t1/2, C1D1 | t1/2, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 6.555 | NA |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 18.35 | 5.500 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 7.624 | 14.27 |
Systemic Clearance (CL) of Docetaxel in Dose-finding Cohort
Plasma docetaxel PK parameters were calculated following a 1-hr infusion of docetaxel given alone (Cycle 1 Day 1) and in combination with BID dosing of PF-03084014 (Cycle 2 Day 1) (NCT01876251)
Timeframe: C1D1, 2, 8, and 21; D1 of subsequent cycles and at EOT (max reached: C12)
| Intervention | liter (L)/hr (Geometric Mean) |
|---|
| CL, C1D1 | CL, C2D1 |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | NA | NA |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | NA | 51.97 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 55.51 | 45.40 |
Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood
As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4. (NCT01876251)
Timeframe: C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12)
| Intervention | percentage change (Mean) |
|---|
| Notch 1 RNA, C1D1 | Notch 1 RNA, C1D2 | Notch 1 RNA, C1D8 | Notch 1 RNA, C1D21 | Notch 1 RNA, EOT | Notch 2 RNA, C1D1 | Notch 2 RNA, C1D2 | Notch 2 RNA, C1D8 | Notch 2 RNA, C1D21 | Notch 2 RNA, EOT | Notch 3 RNA, C1D1 | Notch 3 RNA, C1D2 | Notch 3 RNA, C1D8 | Notch 3 RNA, C1D21 | Notch 4 RNA, C1D1 | Notch 4 RNA, C1D2 | Notch 4 RNA, C1D8 | Notch 4 RNA, C1D21 | Notch 4 RNA, EOT |
|---|
| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 4.431 | -10.647 | 35.305 | 11.214 | 4.177 | 4.351 | -15.441 | 17.234 | 4.985 | -1.558 | 14.765 | -1.186 | -0.154 | -11.274 | 14.309 | 2.484 | -9.427 | -0.500 | -9.975 |
Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood
As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4. (NCT01876251)
Timeframe: C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12)
| Intervention | percentage change (Mean) |
|---|
| Notch 1 RNA, C1D1 | Notch 1 RNA, C1D2 | Notch 1 RNA, C1D8 | Notch 1 RNA, C1D21 | Notch 1 RNA, EOT | Notch 2 RNA, C1D1 | Notch 2 RNA, C1D2 | Notch 2 RNA, C1D8 | Notch 2 RNA, C1D21 | Notch 2 RNA, EOT | Notch 3 RNA, C1D1 | Notch 3 RNA, C1D2 | Notch 3 RNA, C1D8 | Notch 3 RNA, C1D21 | Notch 4 RNA, C1D1 | Notch 4 RNA, C1D2 | Notch 4 RNA, C1D21 | Notch 4 RNA, EOT |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 3.990 | -7.358 | 60.199 | 17.047 | 18.066 | 3.856 | -9.617 | 43.069 | 9.756 | 9.478 | 14.673 | 0.311 | 4.608 | 1.362 | 13.228 | 12.215 | 5.616 | 11.821 |
Percentage Change From Baseline in Notch 1 to 4 Ribonucleic Acid (RNA) in Blood
As PF-03084014 acts on the Notch pathway as an inhibitor, it is of interest to investigate its effects, if any, on the Notch family of receptors, mainly Notch 1-4. (NCT01876251)
Timeframe: C1D1, C1D2, C1D8, C1D21 and EOT (maximum reached: C12)
| Intervention | percentage change (Mean) |
|---|
| Notch 1 RNA, C1D1 | Notch 1 RNA, C1D2 | Notch 1 RNA, C1D8 | Notch 1 RNA, C1D21 | Notch 1 RNA, EOT | Notch 2 RNA, C1D1 | Notch 2 RNA, C1D2 | Notch 2 RNA, C1D8 | Notch 2 RNA, C1D21 | Notch 2 RNA, EOT | Notch 3 RNA, C1D1 | Notch 3 RNA, C1D8 | Notch 4 RNA, C1D1 | Notch 4 RNA, C1D8 | Notch 4 RNA, C1D21 | Notch 4 RNA, EOT |
|---|
| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 4.240 | -5.797 | 32.557 | 6.118 | 5.653 | 4.139 | -12.830 | 15.426 | 2.161 | -1.250 | 14.250 | -2.532 | 13.903 | -13.264 | 0.927 | -3.634 |
Number of Participants With QTc Values Meeting Categorical Summarization Criteria
Criteria for categorical summarization of the time corresponding to the beginning of depolarization to repolarization of the ventricles (QT) corrected for heart rate (QTc) using Bazett's correction (QTcB) or Fridericia's correction (QTcF) included: maximum QTcB or QTcF less than or equal to (<=) 450 milliseconds (msec), 450 to <=480 msec, 480 to <=500 msec, more than (>) 500 msec; maximum QTcB or QTcF changes (increases/decreases) from baseline (BL) less than (<) 30 msec, 30 to <60 msec, more than or equal to (>=) 60 msec. (NCT01876251)
Timeframe: Screening, C1D1, C1D21, Day 1 of subsequent cycles, and EOT (maximum reached: C12)
| Intervention | participants (Number) |
|---|
| QTcB <=450 msec | QTcB 450 to <=480 msec | QTcB 480 to <=500 msec | QTcB >500 msec | QTcF <=450 msec | QTcF 450 to <=480 msec | QTcF 480 to <=500 msec | QTcF >500 msec | QTcB increase from BL <30 msec | QTcB increase from BL 30-<60 msec | QTcB increase from BL >=60 msec | QTcF increase from BL <30 msec | QTcF increase from BL 30-<60 msec | QTcF increase from BL >=60 msec | QTcB decrease from BL <30 msec | QTcB decrease from BL 30-<60 msec | QTcB decrease from BL >=60msec | QTcF decrease from BL <30 msec | QTcF decrease from BL 30-<60 msec | QTcF decrease from BL >=60 msec |
|---|
| PF-03084014 100 mg BID + Docetaxel 100 mg/m^2 | 1 | 1 | 1 | 0 | 2 | 0 | 1 | 0 | 3 | 0 | 0 | 3 | 0 | 0 | 3 | 0 | 0 | 3 | 0 | 0 |
,| PF-03084014 100 mg BID + Docetaxel 75 mg/m^2 | 7 | 6 | 2 | 0 | 13 | 1 | 1 | 0 | 11 | 4 | 0 | 14 | 1 | 0 | 15 | 0 | 0 | 13 | 2 | 0 |
,| PF-03084014 150 mg BID + Docetaxel 75 mg/m^2 | 2 | 8 | 1 | 0 | 6 | 5 | 0 | 0 | 6 | 5 | 0 | 9 | 2 | 0 | 11 | 0 | 0 | 8 | 3 | 0 |
Six-month Progression-free Survival (PFS)
Proportion of participants whose disease does not progress within 6 months of start of treatment (number of patients without progressive disease/total number of patients). Per RECIST v1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (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 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. (NCT01879085)
Timeframe: Up to 6 months (per patient)
| Intervention | proportion of participants (Number) |
|---|
| Phase 2 | 0.473 |
Six-month Overall Survival (OS)
Proportion of participants alive at six months from the start of treatment. (NCT01879085)
Timeframe: Up to 6 months (per patient)
| Intervention | proportion of participants (Number) |
|---|
| Phase 2 | 0.742 |
Objective Response Rate (ORR)
Number of patients with Complete response [CR] + partial response [PR], per RECIST v1.1 criteria . Per RECIST v1.1, CR: Disappearance of all target lesions. Any pathological lymph nodes(whether target or non-target) must have reduction in short axis to <10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10mm short axis);PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters (NCT01879085)
Timeframe: Up to 7 years and 7 months
| Intervention | Participants (Count of Participants) |
|---|
| Phase 2 | 7 |
Progression-free Survival (PFS)
The median length of time from the beginning of study treatment that patients remain alive without progression of their disease (cancer). Per RECIST v1.1, progressive disease (PD) is 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 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. (NCT01879085)
Timeframe: Up to 7 years and 7 months
| Intervention | months (Median) |
|---|
| Phase 2 | 5.552361 |
Phase I: Recommended Phase II Dose of Vorinostat
Recommended Phase ll dose of vorinostat that can be safely combined with gemcitabine and docetaxel. Gemcitabine and docetaxel were given at a fixed dose while vorinostat was dose-escalated using a standard '3+3' design. Dose-limiting toxicity (DLT) is defined as specific study drug-related events experienced during Cycle 1; only DLTs observed in a patient during the first cycle of treatment will be used for the dose escalation decision. (NCT01879085)
Timeframe: During Cycle 1 of treatment
| Intervention | mg/day of Vorinostat (Number) |
|---|
| Combination Therapy: Docetaxel + Gemcitabine + Vorinostat + Pegfilgrastim | 300 |
Overall Survival (OS)
The median length of time from the start of treatment that diagnosed study participants remain alive. (NCT01879085)
Timeframe: Up to 7 years and 7 months
| Intervention | months (Median) |
|---|
| Phase 2 | 11.92608 |
One-year Progression-free Survival (PFS)
Proportion of participants whose disease does not progress within one year of start of treatment (number of patients with progressive disease/total number of patients). Per RECIST v1.1, progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (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 5mm. For non-target lesions, PD: Unequivocal progression of existing non-target lesions. The appearance of one or more new lesions is also considered progression. (NCT01879085)
Timeframe: Up to one year (per patient)
| Intervention | proportion of participants (Number) |
|---|
| Phase 2 | 0.304 |
One-year Overall Survival (OS)
Proportion of participants alive at one year from the start of treatment. (NCT01879085)
Timeframe: Up to one year (per patient)
| Intervention | proportion of participants (Number) |
|---|
| Phase 2 | 0.477 |
Time to PSA Progression
The definition of time to PSA progression is the date (after the initiation of chemotherapy on day 2) that a 25% or greater increase, and an absolute increase of 2ng/mL or more, from the nadir PSA is documented. If there is no decrease in PSA following chemotherapy, then PSA progression is the date for documentation of a 25% increase from the baseline value along with an increase in absolute value of 2ng/mL or more. (NCT01882985)
Timeframe: Up to 4 years
| Intervention | days (Mean) |
|---|
| Treatment (Docetaxel and Lycopene) | 335 |
DOR (Modified RECIST)
DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first. (NCT01903993)
Timeframe: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)
| Intervention | months (Median) |
|---|
| Atezolizumab | 14.9 |
Duration of Response (DOR)
DOR was defined as the duration from the first tumor assessment that supports the participant's objective response (CR or PR, whichever is first recorded) to disease progression or death due to any cause, whichever occurs first. (NCT01903993)
Timeframe: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
| Intervention | months (Median) |
|---|
| Docetaxel | 7.2 |
| Atezolizumab | 18.6 |
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with confirmed objective tumor response, complete response (CR) or partial response (PR), as determined by investigator using RECIST v1.1 criteria. 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 of diameters. (NCT01903993)
Timeframe: Baseline until date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel | 14.7 |
| Atezolizumab | 15.3 |
ORR (Modified RECIST)
ORR was defined as the percentage of participants with confirmed objective tumor response, CR or PR, as determined by investigator using modified RECIST criteria. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to l< 10 mm. PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. (NCT01903993)
Timeframe: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)
| Intervention | percentage of participants (Number) |
|---|
| Atezolizumab | 16.7 |
Overall Survival (OS)
Overall Survival (OS) was defined as the time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as dead at the time of analysis was censored at the date when they were last known to be alive. (NCT01903993)
Timeframe: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
| Intervention | months (Median) |
|---|
| Docetaxel | 9.7 |
| Atezolizumab | 12.6 |
PFS (Modified RECIST)
PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using modified RECIST criteria. PD: 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 is also considered progression. (NCT01903993)
Timeframe: From the time of randomization to the date of death due to any cause or up to data cut off date: 08 May 2015 (up to 21 months)
| Intervention | months (Median) |
|---|
| Atezolizumab | 4.2 |
Progression-Free Survival (PFS)
PFS was defined as the time (in months) between the date of randomization and the date of first documented disease progression or death, whichever occurs first. Disease progression was determined based on investigator assessment using response evaluation criteria In solid tumors (RECIST) v1.1. Progressive disease (PD): at least a 20% increase in the sum of diameters of target lesions including baseline 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. (NCT01903993)
Timeframe: From the time of randomization to the date of death due to any cause or up to data cut off date: 01 Dec 2015 (up to 28 months)
| Intervention | months (Median) |
|---|
| Docetaxel | 3.4 |
| Atezolizumab | 2.7 |
Percentage of Participants Discontinuing Study Drug Due to AEs
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. (NCT01905657)
Timeframe: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab 2 mg/kg | 8.3 |
| Pembrolizumab 10 mg/kg | 7.6 |
| Docetaxel 75 mg/m^2 | 13.6 |
Percentage of Participants Experiencing Adverse Events (AEs)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily had to have a causal relationship with this treatment. An AE is 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 medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the study drug, was also an AE. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. (NCT01905657)
Timeframe: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab 2 mg/kg | 97.6 |
| Pembrolizumab 10 mg/kg | 96.2 |
| Docetaxel 75 mg/m^2 | 96.1 |
Duration of Response (DOR) by RECIST 1.1
DOR is measured from the time measurement criteria were first met for CR/PR (whichever was first recorded) until the first date that death or progressive disease was objectively documented (taking as reference for progressive disease the smallest measurements recorded on study). Non-responders were not included in the analysis. DOR was analyzed using the Kaplan-Meier method and is reported in weeks. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. (NCT01905657)
Timeframe: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
| Intervention | Weeks (Median) |
|---|
| Strongly PD-L1 Positive | All PD-L1 Positive |
|---|
| Docetaxel 75 mg/m^2 | 35 | 27 |
,| Pembrolizumab 10 mg/kg | NA | NA |
,| Pembrolizumab 2 mg/kg | NA | NA |
Overall Response Rate (ORR) by 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 Partial Response (PR; at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters) based on blinded independent central radiologists' review using RECIST 1.1. Per protocol, final analysis for this secondary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. (NCT01905657)
Timeframe: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Strongly PD-L1 Positive | All PD-L1 Positive |
|---|
| Docetaxel 75 mg/m^2 | 7.9 | 9.3 |
,| Pembrolizumab 10 mg/kg | 29.1 | 18.5 |
,| Pembrolizumab 2 mg/kg | 30.2 | 18.0 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. OS was analyzed using the Kaplan-Meier method and is reported in months. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 September (Sep) 2015. (NCT01905657)
Timeframe: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
| Intervention | Months (Median) |
|---|
| Strongly PD-L1 Positive | All PD-L1 Positive |
|---|
| Docetaxel 75 mg/m^2 | 8.2 | 8.5 |
,| Pembrolizumab 10 mg/kg | 17.3 | 12.7 |
,| Pembrolizumab 2 mg/kg | 14.9 | 10.4 |
Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
PFS was defined as the time from the first day of study treatment to the first documented disease progression per RECIST 1.1 based on blinded independent central radiologists' review or death due to any cause, whichever occurred first. Using RECIST 1.1, progressive disease was defined as either a 20% relative increase in the sum of diameters of target lesions, taking as reference the smallest sum on study OR an absolute increase of >5 mm in the sum of lesions, OR the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and is reported in months. Per protocol, final analysis for this primary outcome measure was performed for the first pembrolizumab course and docetaxel treatment arms, with a protocol-specified analysis data cutoff date of 30 Sep 2015. (NCT01905657)
Timeframe: Through pre-specified database cutoff date of 30 Sep 2015 (Up to approximately 24 months)
| Intervention | Months (Median) |
|---|
| Strongly PD-L1 Positive | All PD-L1 Positive |
|---|
| Docetaxel 75 mg/m^2 | 4.1 | 4.0 |
,| Pembrolizumab 10 mg/kg | 5.2 | 4.0 |
,| Pembrolizumab 2 mg/kg | 5.2 | 3.9 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
AUClast is defined as area under the curve from time zero to last quantifiable concentration. (NCT01920061)
Timeframe: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 50210 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 50860 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 44240 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 48870 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 42910 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 46560 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 48350 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
AUClast is defined as area under the curve from time zero to last quantifiable concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1418 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 2748 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 2111 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1594 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1280 |
Number of Participants With Maximum Increase From Baseline in Corrected QT (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 30 to less than (<) 60 msec(borderline) and greater than or equal to (>=) 60 msec (prolonged) were summarized. (NCT01920061)
Timeframe: Baseline, Cycle 1 Day 1 (for Arm B Expansion), Cycle 1 Day 2 (for Arms A, B and C), Cycle 2 Day 1 (for Arms A, B and C), Day 1 for each cycle (Cycles 3-36, for Arms B Expansion and C) and end of treatment (up to 2 years, for Arms B Expansion and C).
| Intervention | Participants (Count of Participants) |
|---|
| Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001857 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001858 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001859 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001860 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001861 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001862 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001863 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001864 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001865 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001866 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001867 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001868 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001853 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001854 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001855 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001856 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001869 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001870 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001873 | Maximum QTcB interval (Bazett's correction) increase from baseline (msec)72001874 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001856 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001857 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001858 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001859 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001860 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001861 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001862 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001863 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001865 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001866 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001867 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001868 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001874 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001864 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001853 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001854 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001855 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001869 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001870 | Maximum QTcF interval (Fridericia's correction) increase from baseline (msec)72001873 |
|---|
| 30 < Change <= 60 | Change > 60 | Change <= 30 |
|---|
| Arm A5: 180 mg PF-05212384 + Docetaxel | 4 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 4 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 2 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 3 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 1 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 3 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 10 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 3 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 10 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 2 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 5 |
| Arm 2: 2L/3L Metastatic | 7 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 0 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 0 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 0 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 0 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 1 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 0 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm 2: 2L/3L Metastatic | 4 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 0 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm 2: 2L/3L Metastatic | 1 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 4 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 5 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 3 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 11 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm 1: 1L Metastasic | 9 |
| Arm 2: 2L/3L Metastatic | 9 |
| Arm 1: 1L Metastasic | 0 |
| Arm 2: 2L/3L Metastatic | 3 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 0 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm 1: 1L Metastasic | 1 |
| Arm 2: 2L/3L Metastatic | 0 |
Number of Participants With Maximum Corrected QT (QTc) Interval Meeting Pre-defined Criteria
QT interval corrected using Fridericia's formula (QTcF) and Bazette's formula (QTcB): QT interval (time corresponding to the beginning of depolarization to re-polarization of the ventricles) divided by cube root of RR interval. Maximum QTcF was categorized as less than (<) 450 milliseconds (msec), 450 msec to 480 msec, 480 msec to 500 msec, and more than (>) 500 msec. (NCT01920061)
Timeframe: Baseline, Cycle 1 Day 1 (for Arm B Expansion), Cycle 1 Day 2 (for Arms A, B and C), Cycle 2 Day 1 (for Arms A, B and C), Day 1 for each cycle (Cycles 3-36, for Arms B Expansion and C) and end of treatment (up to 2 years, for Arms B Expansion and C).
| Intervention | Participants (Count of Participants) |
|---|
| Maximum QTcB interval (Bazett's correction) (msec)72001861 | Maximum QTcB interval (Bazett's correction) (msec)72001862 | Maximum QTcB interval (Bazett's correction) (msec)72001863 | Maximum QTcB interval (Bazett's correction) (msec)72001865 | Maximum QTcB interval (Bazett's correction) (msec)72001866 | Maximum QTcB interval (Bazett's correction) (msec)72001867 | Maximum QTcB interval (Bazett's correction) (msec)72001868 | Maximum QTcB interval (Bazett's correction) (msec)72001869 | Maximum QTcB interval (Bazett's correction) (msec)72001870 | Maximum QTcB interval (Bazett's correction) (msec)72001873 | Maximum QTcB interval (Bazett's correction) (msec)72001874 | Maximum QTcB interval (Bazett's correction) (msec)72001853 | Maximum QTcB interval (Bazett's correction) (msec)72001860 | Maximum QTcB interval (Bazett's correction) (msec)72001854 | Maximum QTcB interval (Bazett's correction) (msec)72001855 | Maximum QTcB interval (Bazett's correction) (msec)72001856 | Maximum QTcB interval (Bazett's correction) (msec)72001857 | Maximum QTcB interval (Bazett's correction) (msec)72001858 | Maximum QTcB interval (Bazett's correction) (msec)72001859 | Maximum QTcB interval (Bazett's correction) (msec)72001864 | Maximum QTcF interval (Fridericia's correction) (msec)72001857 | Maximum QTcF interval (Fridericia's correction) (msec)72001860 | Maximum QTcF interval (Fridericia's correction) (msec)72001861 | Maximum QTcF interval (Fridericia's correction) (msec)72001862 | Maximum QTcF interval (Fridericia's correction) (msec)72001863 | Maximum QTcF interval (Fridericia's correction) (msec)72001864 | Maximum QTcF interval (Fridericia's correction) (msec)72001865 | Maximum QTcF interval (Fridericia's correction) (msec)72001866 | Maximum QTcF interval (Fridericia's correction) (msec)72001867 | Maximum QTcF interval (Fridericia's correction) (msec)72001868 | Maximum QTcF interval (Fridericia's correction) (msec)72001869 | Maximum QTcF interval (Fridericia's correction) (msec)72001870 | Maximum QTcF interval (Fridericia's correction) (msec)72001873 | Maximum QTcF interval (Fridericia's correction) (msec)72001855 | Maximum QTcF interval (Fridericia's correction) (msec)72001874 | Maximum QTcF interval (Fridericia's correction) (msec)72001853 | Maximum QTcF interval (Fridericia's correction) (msec)72001854 | Maximum QTcF interval (Fridericia's correction) (msec)72001856 | Maximum QTcF interval (Fridericia's correction) (msec)72001858 | Maximum QTcF interval (Fridericia's correction) (msec)72001859 |
|---|
| > 500 | < 450 | 450 <= Value <= 480 | 480 < Value <=500 |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 3 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 3 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 1 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 2 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 2 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 2 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 7 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 2 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 11 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 2 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 5 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm 1: 1L Metastasic | 5 |
| Arm 2: 2L/3L Metastatic | 3 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 2 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 3 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 1 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 1 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 0 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 1 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 3 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 3 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm 1: 1L Metastasic | 4 |
| Arm 2: 2L/3L Metastatic | 7 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 0 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm 1: 1L Metastasic | 0 |
| Arm 2: 2L/3L Metastatic | 2 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 0 |
| Arm 1: 1L Metastasic | 1 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 4 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 5 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 3 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 3 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 2 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 4 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 3 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 3 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 3 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 10 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 4 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 14 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 4 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm 1: 1L Metastasic | 8 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 3 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 1 |
| Arm 2: 2L/3L Metastatic | 5 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 |
| Arm 2: 2L/3L Metastatic | 0 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 0 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 0 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 0 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 0 |
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Hematology
Laboratory abnormalities were graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: anemia,hemoglobin increased, platelets, white blood cells, absolute neutrophils,lymphocyte count increased, lymphopenia. (NCT01920061)
Timeframe: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | Participants (Count of Participants) |
|---|
| Anemia72001855 | Anemia72001853 | Anemia72001874 | Anemia72001854 | Anemia72001856 | Anemia72001857 | Anemia72001858 | Anemia72001859 | Anemia72001860 | Anemia72001861 | Anemia72001862 | Anemia72001863 | Anemia72001864 | Anemia72001865 | Anemia72001866 | Anemia72001867 | Anemia72001868 | Anemia72001869 | Anemia72001870 | Anemia72001873 | Hemoglobin increased72001853 | Hemoglobin increased72001873 | Hemoglobin increased72001862 | Hemoglobin increased72001854 | Hemoglobin increased72001855 | Hemoglobin increased72001856 | Hemoglobin increased72001857 | Hemoglobin increased72001858 | Hemoglobin increased72001859 | Hemoglobin increased72001860 | Hemoglobin increased72001861 | Hemoglobin increased72001863 | Hemoglobin increased72001864 | Hemoglobin increased72001865 | Hemoglobin increased72001866 | Hemoglobin increased72001867 | Hemoglobin increased72001868 | Hemoglobin increased72001869 | Hemoglobin increased72001870 | Hemoglobin increased72001874 | Lymphocyte count increased72001855 | Lymphocyte count increased72001867 | Lymphocyte count increased72001868 | Lymphocyte count increased72001873 | Lymphocyte count increased72001874 | Lymphocyte count increased72001853 | Lymphocyte count increased72001854 | Lymphocyte count increased72001856 | Lymphocyte count increased72001857 | Lymphocyte count increased72001858 | Lymphocyte count increased72001859 | Lymphocyte count increased72001860 | Lymphocyte count increased72001861 | Lymphocyte count increased72001862 | Lymphocyte count increased72001863 | Lymphocyte count increased72001864 | Lymphocyte count increased72001865 | Lymphocyte count increased72001866 | Lymphocyte count increased72001869 | Lymphocyte count increased72001870 | Lymphopenia72001855 | Lymphopenia72001862 | Lymphopenia72001865 | Lymphopenia72001868 | Lymphopenia72001853 | Lymphopenia72001854 | Lymphopenia72001856 | Lymphopenia72001857 | Lymphopenia72001858 | Lymphopenia72001859 | Lymphopenia72001860 | Lymphopenia72001861 | Lymphopenia72001863 | Lymphopenia72001864 | Lymphopenia72001866 | Lymphopenia72001867 | Lymphopenia72001869 | Lymphopenia72001870 | Lymphopenia72001873 | Lymphopenia72001874 | Absolute neutrophils72001853 | Absolute neutrophils72001855 | Absolute neutrophils72001865 | Absolute neutrophils72001856 | Absolute neutrophils72001862 | Absolute neutrophils72001873 | Absolute neutrophils72001874 | Absolute neutrophils72001854 | Absolute neutrophils72001857 | Absolute neutrophils72001858 | Absolute neutrophils72001859 | Absolute neutrophils72001860 | Absolute neutrophils72001861 | Absolute neutrophils72001863 | Absolute neutrophils72001864 | Absolute neutrophils72001866 | Absolute neutrophils72001867 | Absolute neutrophils72001868 | Absolute neutrophils72001869 | Absolute neutrophils72001870 | Platelets72001873 | Platelets72001855 | Platelets72001853 | Platelets72001854 | Platelets72001856 | Platelets72001857 | Platelets72001858 | Platelets72001859 | Platelets72001860 | Platelets72001861 | Platelets72001862 | Platelets72001863 | Platelets72001864 | Platelets72001865 | Platelets72001866 | Platelets72001867 | Platelets72001868 | Platelets72001869 | Platelets72001870 | Platelets72001874 | White blood cells72001853 | White blood cells72001854 | White blood cells72001855 | White blood cells72001856 | White blood cells72001857 | White blood cells72001858 | White blood cells72001859 | White blood cells72001860 | White blood cells72001861 | White blood cells72001862 | White blood cells72001863 | White blood cells72001864 | White blood cells72001865 | White blood cells72001866 | White blood cells72001867 | White blood cells72001868 | White blood cells72001869 | White blood cells72001870 | White blood cells72001873 | White blood cells72001874 |
|---|
| Grade 3 | Grade 4 | Grade 0 | Grade 1 | Grade 2 |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 4 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 3 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 5 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 2 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 3 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 2 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm 1: 1L Metastasic | 6 |
| Arm 2: 2L/3L Metastatic | 8 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 10 |
| Arm 1: 1L Metastasic | 9 |
| Arm 1: 1L Metastasic | 1 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 4 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 3 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 4 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 3 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 3 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 3 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 9 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 5 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 2 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 7 |
| Arm 1: 1L Metastasic | 10 |
| Arm 2: 2L/3L Metastatic | 12 |
| Arm 2: 2L/3L Metastatic | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 3 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 7 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 6 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 2 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 4 |
| Arm 1: 1L Metastasic | 3 |
| Arm 2: 2L/3L Metastatic | 4 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 14 |
| Arm 1: 1L Metastasic | 4 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 3 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 5 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 2 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 3 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 5 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 1 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 6 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 15 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 4 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm 1: 1L Metastasic | 7 |
| Arm 2: 2L/3L Metastatic | 7 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 3 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 4 |
| Arm 1: 1L Metastasic | 2 |
| Arm 2: 2L/3L Metastatic | 3 |
| Arm 1: 1L Metastasic | 0 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 1 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 3 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 2 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 10 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 3 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 0 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 2 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 1 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 2 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 3 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 5 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 1 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 0 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 1 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 1 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 5 |
| Arm 2: 2L/3L Metastatic | 5 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 2 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 2 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 0 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 4 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 1 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 1 |
| Arm 2: 2L/3L Metastatic | 1 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 1 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 1 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 2 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 0 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 0 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 0 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 0 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 0 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm 2: 2L/3L Metastatic | 0 |
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Coagulation
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: partial thromboplastin time and prothrombin time international normalized ratio(INR). (NCT01920061)
Timeframe: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | Participants (Count of Participants) |
|---|
| Partial thromboplastin time72001853 | Partial thromboplastin time72001854 | Partial thromboplastin time72001874 | Partial thromboplastin time72001855 | Partial thromboplastin time72001856 | Partial thromboplastin time72001857 | Partial thromboplastin time72001858 | Partial thromboplastin time72001859 | Partial thromboplastin time72001860 | Partial thromboplastin time72001861 | Partial thromboplastin time72001862 | Partial thromboplastin time72001863 | Partial thromboplastin time72001864 | Partial thromboplastin time72001865 | Partial thromboplastin time72001866 | Partial thromboplastin time72001867 | Partial thromboplastin time72001868 | Partial thromboplastin time72001869 | Partial thromboplastin time72001870 | Partial thromboplastin time72001873 | Prothrombin time INR72001853 | Prothrombin time INR72001854 | Prothrombin time INR72001855 | Prothrombin time INR72001856 | Prothrombin time INR72001857 | Prothrombin time INR72001858 | Prothrombin time INR72001859 | Prothrombin time INR72001860 | Prothrombin time INR72001861 | Prothrombin time INR72001862 | Prothrombin time INR72001863 | Prothrombin time INR72001864 | Prothrombin time INR72001865 | Prothrombin time INR72001866 | Prothrombin time INR72001867 | Prothrombin time INR72001868 | Prothrombin time INR72001869 | Prothrombin time INR72001870 | Prothrombin time INR72001873 | Prothrombin time INR72001874 |
|---|
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 4 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 4 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 3 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 2 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 5 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 7 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 2 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 4 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm 1: 1L Metastasic | 9 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 1 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 2 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 6 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm 1: 1L Metastasic | 1 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 1 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm 2: 2L/3L Metastatic | 1 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm 2: 2L/3L Metastatic | 0 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 2 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 3 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 4 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 3 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 3 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 3 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 2 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 3 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 9 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 5 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 13 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 4 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm 1: 1L Metastasic | 8 |
| Arm 2: 2L/3L Metastatic | 10 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 3 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 1 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 1 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 1 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 1 |
| Arm 1: 1L Metastasic | 2 |
| Arm 2: 2L/3L Metastatic | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 0 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 0 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 0 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 0 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 0 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 0 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 0 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 0 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm 1: 1L Metastasic | 0 |
Number of Participants With Laboratory Abnormalities by Severity (All Cycles) - Chemistry
Laboratory abnormalities were graded per NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated) and those with at least 1 participant are presented here. Following parameters were analyzed for laboratory examination: alanine aminotransferase (ALT), alkaline phosphatase, aspartate aminotransferase (AST), total bilirubin, creatinine, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, and hypophosphatemia. (NCT01920061)
Timeframe: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | Participants (Count of Participants) |
|---|
| ALT72001858 | ALT72001859 | ALT72001860 | ALT72001861 | ALT72001862 | ALT72001863 | ALT72001864 | ALT72001865 | ALT72001866 | ALT72001867 | ALT72001868 | ALT72001870 | ALT72001873 | ALT72001874 | ALT72001869 | ALT72001853 | ALT72001854 | ALT72001855 | ALT72001856 | ALT72001857 | Alkaline phosphatase72001858 | Alkaline phosphatase72001859 | Alkaline phosphatase72001860 | Alkaline phosphatase72001861 | Alkaline phosphatase72001862 | Alkaline phosphatase72001863 | Alkaline phosphatase72001864 | Alkaline phosphatase72001866 | Alkaline phosphatase72001868 | Alkaline phosphatase72001869 | Alkaline phosphatase72001870 | Alkaline phosphatase72001873 | Alkaline phosphatase72001874 | Alkaline phosphatase72001854 | Alkaline phosphatase72001867 | Alkaline phosphatase72001853 | Alkaline phosphatase72001855 | Alkaline phosphatase72001856 | Alkaline phosphatase72001857 | Alkaline phosphatase72001865 | AST72001858 | AST72001859 | AST72001860 | AST72001861 | AST72001862 | AST72001863 | AST72001864 | AST72001865 | AST72001866 | AST72001867 | AST72001868 | AST72001869 | AST72001870 | AST72001873 | AST72001874 | AST72001853 | AST72001854 | AST72001855 | AST72001856 | AST72001857 | Bilirubin (total)72001858 | Bilirubin (total)72001859 | Bilirubin (total)72001860 | Bilirubin (total)72001861 | Bilirubin (total)72001862 | Bilirubin (total)72001863 | Bilirubin (total)72001864 | Bilirubin (total)72001865 | Bilirubin (total)72001866 | Bilirubin (total)72001867 | Bilirubin (total)72001868 | Bilirubin (total)72001869 | Bilirubin (total)72001870 | Bilirubin (total)72001873 | Bilirubin (total)72001874 | Bilirubin (total)72001853 | Bilirubin (total)72001854 | Bilirubin (total)72001855 | Bilirubin (total)72001856 | Bilirubin (total)72001857 | Creatinine72001858 | Creatinine72001859 | Creatinine72001860 | Creatinine72001861 | Creatinine72001862 | Creatinine72001863 | Creatinine72001864 | Creatinine72001865 | Creatinine72001866 | Creatinine72001867 | Creatinine72001868 | Creatinine72001869 | Creatinine72001870 | Creatinine72001873 | Creatinine72001874 | Creatinine72001853 | Creatinine72001854 | Creatinine72001855 | Creatinine72001856 | Creatinine72001857 | Hypercalcemia72001858 | Hypercalcemia72001859 | Hypercalcemia72001860 | Hypercalcemia72001861 | Hypercalcemia72001862 | Hypercalcemia72001863 | Hypercalcemia72001864 | Hypercalcemia72001865 | Hypercalcemia72001866 | Hypercalcemia72001867 | Hypercalcemia72001868 | Hypercalcemia72001869 | Hypercalcemia72001870 | Hypercalcemia72001873 | Hypercalcemia72001874 | Hypercalcemia72001853 | Hypercalcemia72001854 | Hypercalcemia72001855 | Hypercalcemia72001856 | Hypercalcemia72001857 | Hyperglycemia72001858 | Hyperglycemia72001859 | Hyperglycemia72001860 | Hyperglycemia72001861 | Hyperglycemia72001862 | Hyperglycemia72001863 | Hyperglycemia72001864 | Hyperglycemia72001865 | Hyperglycemia72001866 | Hyperglycemia72001867 | Hyperglycemia72001868 | Hyperglycemia72001869 | Hyperglycemia72001870 | Hyperglycemia72001873 | Hyperglycemia72001874 | Hyperglycemia72001857 | Hyperglycemia72001853 | Hyperglycemia72001854 | Hyperglycemia72001855 | Hyperglycemia72001856 | Hyperkalemia72001857 | Hyperkalemia72001858 | Hyperkalemia72001859 | Hyperkalemia72001860 | Hyperkalemia72001861 | Hyperkalemia72001862 | Hyperkalemia72001863 | Hyperkalemia72001864 | Hyperkalemia72001865 | Hyperkalemia72001866 | Hyperkalemia72001867 | Hyperkalemia72001868 | Hyperkalemia72001869 | Hyperkalemia72001870 | Hyperkalemia72001873 | Hyperkalemia72001874 | Hyperkalemia72001853 | Hyperkalemia72001854 | Hyperkalemia72001855 | Hyperkalemia72001856 | Hypermagnesemia72001857 | Hypermagnesemia72001858 | Hypermagnesemia72001859 | Hypermagnesemia72001860 | Hypermagnesemia72001861 | Hypermagnesemia72001862 | Hypermagnesemia72001863 | Hypermagnesemia72001864 | Hypermagnesemia72001865 | Hypermagnesemia72001866 | Hypermagnesemia72001867 | Hypermagnesemia72001868 | Hypermagnesemia72001869 | Hypermagnesemia72001870 | Hypermagnesemia72001873 | Hypermagnesemia72001874 | Hypermagnesemia72001853 | Hypermagnesemia72001854 | Hypermagnesemia72001855 | Hypermagnesemia72001856 | Hypernatremia72001857 | Hypernatremia72001858 | Hypernatremia72001859 | Hypernatremia72001860 | Hypernatremia72001861 | Hypernatremia72001862 | Hypernatremia72001863 | Hypernatremia72001864 | Hypernatremia72001865 | Hypernatremia72001866 | Hypernatremia72001867 | Hypernatremia72001868 | Hypernatremia72001869 | Hypernatremia72001870 | Hypernatremia72001873 | Hypernatremia72001874 | Hypernatremia72001853 | Hypernatremia72001854 | Hypernatremia72001855 | Hypernatremia72001856 | Hypoalbuminemia72001857 | Hypoalbuminemia72001858 | Hypoalbuminemia72001859 | Hypoalbuminemia72001860 | Hypoalbuminemia72001861 | Hypoalbuminemia72001862 | Hypoalbuminemia72001863 | Hypoalbuminemia72001864 | Hypoalbuminemia72001865 | Hypoalbuminemia72001866 | Hypoalbuminemia72001867 | Hypoalbuminemia72001868 | Hypoalbuminemia72001869 | Hypoalbuminemia72001870 | Hypoalbuminemia72001873 | Hypoalbuminemia72001874 | Hypoalbuminemia72001853 | Hypoalbuminemia72001854 | Hypoalbuminemia72001855 | Hypoalbuminemia72001856 | Hypocalcemia72001857 | Hypocalcemia72001858 | Hypocalcemia72001859 | Hypocalcemia72001860 | Hypocalcemia72001861 | Hypocalcemia72001862 | Hypocalcemia72001863 | Hypocalcemia72001864 | Hypocalcemia72001865 | Hypocalcemia72001866 | Hypocalcemia72001867 | Hypocalcemia72001868 | Hypocalcemia72001869 | Hypocalcemia72001870 | Hypocalcemia72001873 | Hypocalcemia72001874 | Hypocalcemia72001853 | Hypocalcemia72001854 | Hypocalcemia72001855 | Hypocalcemia72001856 | Hypoglycemia72001857 | Hypoglycemia72001858 | Hypoglycemia72001859 | Hypoglycemia72001860 | Hypoglycemia72001861 | Hypoglycemia72001862 | Hypoglycemia72001863 | Hypoglycemia72001864 | Hypoglycemia72001865 | Hypoglycemia72001866 | Hypoglycemia72001867 | Hypoglycemia72001868 | Hypoglycemia72001869 | Hypoglycemia72001870 | Hypoglycemia72001873 | Hypoglycemia72001874 | Hypoglycemia72001853 | Hypoglycemia72001854 | Hypoglycemia72001855 | Hypoglycemia72001856 | Hypokalemia72001858 | Hypokalemia72001859 | Hypokalemia72001860 | Hypokalemia72001861 | Hypokalemia72001862 | Hypokalemia72001863 | Hypokalemia72001864 | Hypokalemia72001865 | Hypokalemia72001866 | Hypokalemia72001867 | Hypokalemia72001868 | Hypokalemia72001869 | Hypokalemia72001870 | Hypokalemia72001873 | Hypokalemia72001874 | Hypokalemia72001853 | Hypokalemia72001854 | Hypokalemia72001855 | Hypokalemia72001856 | Hypokalemia72001857 | Hypomagnesemia72001857 | Hypomagnesemia72001858 | Hypomagnesemia72001859 | Hypomagnesemia72001860 | Hypomagnesemia72001861 | Hypomagnesemia72001862 | Hypomagnesemia72001863 | Hypomagnesemia72001864 | Hypomagnesemia72001865 | Hypomagnesemia72001866 | Hypomagnesemia72001867 | Hypomagnesemia72001868 | Hypomagnesemia72001869 | Hypomagnesemia72001870 | Hypomagnesemia72001873 | Hypomagnesemia72001874 | Hypomagnesemia72001853 | Hypomagnesemia72001854 | Hypomagnesemia72001855 | Hypomagnesemia72001856 | Hyponatremia72001858 | Hyponatremia72001859 | Hyponatremia72001860 | Hyponatremia72001861 | Hyponatremia72001862 | Hyponatremia72001863 | Hyponatremia72001864 | Hyponatremia72001865 | Hyponatremia72001866 | Hyponatremia72001867 | Hyponatremia72001868 | Hyponatremia72001869 | Hyponatremia72001870 | Hyponatremia72001873 | Hyponatremia72001874 | Hyponatremia72001853 | Hyponatremia72001854 | Hyponatremia72001855 | Hyponatremia72001856 | Hyponatremia72001857 | Hypophosphatemia72001857 | Hypophosphatemia72001858 | Hypophosphatemia72001859 | Hypophosphatemia72001860 | Hypophosphatemia72001861 | Hypophosphatemia72001862 | Hypophosphatemia72001863 | Hypophosphatemia72001864 | Hypophosphatemia72001865 | Hypophosphatemia72001866 | Hypophosphatemia72001867 | Hypophosphatemia72001868 | Hypophosphatemia72001869 | Hypophosphatemia72001870 | Hypophosphatemia72001873 | Hypophosphatemia72001874 | Hypophosphatemia72001853 | Hypophosphatemia72001854 | Hypophosphatemia72001855 | Hypophosphatemia72001856 |
|---|
| Grade 4 | Grade 0 | Grade 1 | Grade 2 | Grade 3 |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 3 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 5 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 10 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 3 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm 1: 1L Metastasic | 7 |
| Arm 2: 2L/3L Metastatic | 7 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 4 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 4 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 2 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm 1: 1L Metastasic | 2 |
| Arm 2: 2L/3L Metastatic | 5 |
| Arm 1: 1L Metastasic | 1 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 2 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 2 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 1 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 1 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 1 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 8 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 3 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 9 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 2 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 7 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm 1: 1L Metastasic | 10 |
| Arm 2: 2L/3L Metastatic | 8 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 1 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 1 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 2 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 1 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 5 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm 1: 1L Metastasic | 0 |
| Arm 2: 2L/3L Metastatic | 3 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 0 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 0 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 1 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm 2: 2L/3L Metastatic | 1 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 0 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 0 |
| Arm 2: 2L/3L Metastatic | 0 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 0 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 9 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 12 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 5 |
| Arm 1: 1L Metastasic | 5 |
| Arm 2: 2L/3L Metastatic | 6 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 4 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 3 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 3 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 3 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 3 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 5 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 13 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 4 |
| Arm 2: 2L/3L Metastatic | 12 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm 2: 2L/3L Metastatic | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 6 |
| Arm 1: 1L Metastasic | 6 |
| Arm 2: 2L/3L Metastatic | 4 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 3 |
| Arm 1: 1L Metastasic | 4 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 5 |
| Arm 1: 1L Metastasic | 8 |
| Arm 2: 2L/3L Metastatic | 10 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 6 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 4 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 1 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 3 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 8 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 3 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 2 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 2 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 10 |
| Arm 1: 1L Metastasic | 9 |
| Arm 2: 2L/3L Metastatic | 11 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 15 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 2 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 4 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 4 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 11 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 5 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 3 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 3 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 2 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 3 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 0 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 4 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 1 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 4 |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 14 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 3 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 1 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 2 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 2 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1 |
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 0 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 0 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Triple Negative Breast Cancer - Arm B
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | BRAF - V600E (mutation detected) | BRAF - V600E (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm B | 0 | 38.5 | 0 | 38.5 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Transitional Cell Carcinoma - Arm B
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | BRAF - V600E (mutation detected) | BRAF - V600E (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm B | 0 | 28.6 | 0 | 71.4 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 14.3 | 85.7 | 0 | 100.0 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Prostate Cancer - Arm A
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | BRAF - V600E (mutation detected) | BRAF - V600E (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm A | 0 | 66.7 | 0 | 33.3 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
Mean Serum Biomarkers for Insulin - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | microunits/mL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of head and neck cancer | In population of oesophageal carcinoma |
|---|
| Arm C | 318.62 | 18.26 | 289.32 | 436.94 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Ovarian Cancer - Arm B
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation category was BRAF mutation status. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm B | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 50.0 | 50.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Non-Small Cell Lung Cancer - Arms A, B and C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | BRAF - V600E (mutation detected) | BRAF - V600E (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm A | 0 | 14.3 | 0 | 85.7 | 0 | 85.7 | 0 | 85.7 | 14.3 | 71.4 | 0 | 85.7 | 0 | 85.7 | 0 | 85.7 | 0 | 85.7 |
,| Arm B | 0 | 80.0 | 0 | 20.0 | 5 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
,| Arm C | 0 | 25.0 | 0 | 75.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Head and Neck Cancer - Arm C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | BRAF - V600E (mutation detected) | BRAF - V600E (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm C | 0 | 10.0 | 0 | 90.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Breast Cancer - Arms A and C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | BRAF - V600E (mutation detected) | BRAF - V600E (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm A | 0 | 33.3 | 0 | 66.7 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
,| Arm C | 0 | 40.0 | 0 | 40.0 | 0 | 80.0 | 0 | 80.0 | 0 | 80.0 | 0 | 80.0 | 0 | 80.0 | 0 | 80.0 | 0 | 80.0 |
Number of Participants With Vital Signs Data Meeting Pre-defined Criteria
Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in sitting position. (NCT01920061)
Timeframe: From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment). Maximum duration between first and last dose: 842 days.
| Intervention | Participants (Count of Participants) |
|---|
| Sitting SBP<=100 mmHg | Sitting SBP>=160 mmHg | Sitting DBP<=60 mmHg | Sitting DBP>=100 mmHg | Sitting heart rate<50 bpm | Sitting heart rate>120 bpm | Max increase from baseline in sitting SBP>=20 mmHg | Max increase from baseline in sitting SBP>=40 mmHg | Max increase from baseline in sitting SBP>=60 mmHg | Max increase from baseline in sitting DBP>=10 mmHg | Max increase from baseline in sitting DBP>=20 mmHg | Max increase from baseline in sitting DBP>=30 mmHg |
|---|
| Arm 1: 1L Metastasic | 6 | 1 | 7 | 0 | 0 | 0 | 4 | 3 | 0 | 6 | 1 | 0 |
,| Arm 2: 2L/3L Metastatic | 6 | 2 | 6 | 0 | 0 | 0 | 4 | 1 | 0 | 5 | 3 | 0 |
,| Arm A1: 90 mg PF-05212384 + Docetaxel | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 |
,| Arm A2: 110 mg PF-05212384 + Docetaxel | 2 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
,| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 2 | 0 | 0 |
,| Arm A4: 150 mg PF-05212384 + Docetaxel | 3 | 0 | 2 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 0 |
,| Arm A5: 180 mg PF-05212384 + Docetaxel | 1 | 0 | 2 | 0 | 0 | 0 | 2 | 0 | 0 | 2 | 1 | 0 |
,| Arm B1: 90 mg PF-05212384 + Cisplatin | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Arm B2: 110 mg PF-05212384 + Cisplatin | 1 | 1 | 2 | 1 | 0 | 0 | 1 | 1 | 1 | 2 | 1 | 1 |
,| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 0 |
,| Arm B4: 150 mg PF-05212384 + Cisplatin | 2 | 0 | 2 | 0 | 0 | 2 | 1 | 0 | 0 | 1 | 1 | 0 |
,| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 2 | 0 | 0 |
,| Arm B6: 215 mg PF-05212384 + Cisplatin | 3 | 0 | 2 | 0 | 0 | 0 | 4 | 0 | 0 | 8 | 3 | 0 |
,| Arm B7: 260 mg PF-05212384 + Cisplatin | 2 | 0 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 0 |
,| Arm B8: 310 mg PF-05212384 + Cisplatin | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 1 | 0 |
,| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 4 | 1 | 5 | 2 | 1 | 1 | 3 | 1 | 1 | 4 | 0 | 0 |
,| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 1 | 1 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
,| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 2 | 0 | 2 | 0 | 0 | 0 | 4 | 1 | 0 | 3 | 2 | 0 |
,| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
,| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Mean Serum Biomarkers for Insulin - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | microunits/mL (Mean) |
|---|
| In population of NSCLC | In population of OC | In population of TCC | In population of TNBC |
|---|
| Arm B | 710.50 | 12.50 | 20.68 | 81.16 |
Number of Participants With Treatment-Emergent Adverse Events (All Causality) - Arms A, B, C and B Expansion
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participants administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Treatment Emergent AEs were those occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment, or those were seen prior to the start of study treatment but increased in Common Terminology Criteria for Adverse Events (CTCAE) grade after the start of study treatment and within 28 days after final dose of study treatment. AEs were graded by the investigator according to the CTCAE version 4.03 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE. (NCT01920061)
Timeframe: From the first dose of study drugs up to 28 days after the last dose of study drugs. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1 AEs | Grade 2 AEs | Grade 3 AEs | Grade 4 AEs | Grade 5 AEs |
|---|
| Arm 1: 1L Metastasic | 0 | 1 | 8 | 0 | 1 |
,| Arm 2: 2L/3L Metastatic | 0 | 3 | 7 | 2 | 0 |
,| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 | 0 | 2 | 2 | 0 |
,| Arm A2: 110 mg PF-05212384 + Docetaxel | 0 | 0 | 2 | 2 | 1 |
,| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 | 0 | 2 | 1 | 0 |
,| Arm A4: 150 mg PF-05212384 + Docetaxel | 0 | 0 | 0 | 2 | 1 |
,| Arm A5: 180 mg PF-05212384 + Docetaxel | 0 | 0 | 0 | 5 | 0 |
,| Arm B1: 90 mg PF-05212384 + Cisplatin | 1 | 1 | 2 | 0 | 0 |
,| Arm B2: 110 mg PF-05212384 + Cisplatin | 0 | 0 | 2 | 1 | 0 |
,| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 | 0 | 2 | 0 | 1 |
,| Arm B4: 150 mg PF-05212384 + Cisplatin | 0 | 0 | 1 | 2 | 0 |
,| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 | 1 | 1 | 0 | 1 |
,| Arm B6: 215 mg PF-05212384 + Cisplatin | 0 | 0 | 9 | 1 | 0 |
,| Arm B7: 260 mg PF-05212384 + Cisplatin | 0 | 2 | 2 | 0 | 1 |
,| Arm B8: 310 mg PF-05212384 + Cisplatin | 0 | 0 | 2 | 0 | 0 |
,| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 1 | 5 | 6 | 1 | 2 |
,| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 0 | 0 | 4 | 0 | 0 |
,| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0 | 3 | 4 | 0 | 0 |
,| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 | 3 | 0 | 0 | 0 |
,| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 | 1 | 2 | 0 | 0 |
Number of Participants With Dose Limiting Toxicities (DLTs) - Arms A, B and C
DLT was defined as any of the following adverse events (AEs) attributable to the combination: (1) hematologic: grade 4 neutropenia lasting >7 days; febrile neutropenia; grade >=3 neutropenia with infection; grade 3 thrombocytopenia with bleeding; grade 4 thrombocytopenia; (2) non-hematologic: grade >=2 pneumonitis; grade>=3 toxicities, except pneumonitis, and excluding those that had not been maximally treated; persistent, intolerable toxicities which resulted in the failure to deliver at least 3 of the 4 doses of PF-05212384 for Arms A and B or at least 3 of the 4 doses of PF-05212384 and 75% of dacomitinib for Arm C during the first cycle; the persistent, intolerable toxicities which result in delay of the start of the second cycle by more than 2 weeks relative to the scheduled start; in an asymptomatic participant, the grade 3 QTc prolongation persists after correction of any reversible causes. (NCT01920061)
Timeframe: Up to 21 days
| Intervention | Participants (Count of Participants) |
|---|
| With DLT | No DLT | Data missing |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 | 4 | 0 |
,| Arm A2: 110 mg PF-05212384 + Docetaxel | 0 | 3 | 0 |
,| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 | 2 | 1 |
,| Arm A4: 150 mg PF-05212384 + Docetaxel | 0 | 3 | 0 |
,| Arm A5: 180 mg PF-05212384 + Docetaxel | 1 | 1 | 0 |
,| Arm B1: 90 mg PF-05212384 + Cisplatin | 0 | 3 | 0 |
,| Arm B2: 110 mg PF-05212384 + Cisplatin | 0 | 3 | 0 |
,| Arm B3: 130 mg PF-05212384 + Cisplatin | 0 | 3 | 0 |
,| Arm B4: 150 mg PF-05212384 + Cisplatin | 0 | 3 | 0 |
,| Arm B5: 180 mg PF-05212384 + Cisplatin | 0 | 3 | 0 |
,| Arm B6: 215 mg PF-05212384 + Cisplatin | 0 | 8 | 0 |
,| Arm B7: 260 mg PF-05212384 + Cisplatin | 0 | 3 | 0 |
,| Arm B8: 310 mg PF-05212384 + Cisplatin | 2 | 0 | 0 |
,| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0 | 13 | 0 |
,| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 2 | 0 | 0 |
,| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 2 | 5 | 0 |
,| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 | 3 | 0 |
,| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0 | 2 | 0 |
Mean Serum Biomarkers for Insulin - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | microunits/mL (Mean) |
|---|
| In population of NSCLC | In population of OC | In population of TCC | In population of TNBC |
|---|
| Arm B | 832.87 | 80.30 | 41.65 | 56.69 |
Mean Serum Biomarkers for Insulin - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | microunits/mL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of prostate cancer |
|---|
| Arm A | 19.17 | 22.34 | 13.73 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | hr (Median) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 2.08 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 2.12 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 2.10 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 2.00 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 2.05 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 2.01 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 2.00 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Maximum Observed Plasma Concentration (Cmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1840 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 695.9 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 2457 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1424 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1300 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | hr (Median) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 4.08 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 6.00 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6.00 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 5.97 |
Maximum Observed Plasma Concentration (Cmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 3867 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 4201 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 3205 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 4086 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 3130 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 3665 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 3211 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Duration of Response - Arm B Expansion
Duration of response was calculated from first date of partial response (PR) or complete response (CR) to the date of progression or death due to any cause. In the event of no progression or death, the last tumor assessment date without progression was used in this calculation. (NCT01920061)
Timeframe: Baseline up to 18 months.
| Intervention | month (Median) |
|---|
| Arm 1: 1L Metastasic | 6.9 |
| Arm 2: 2L/3L Metastatic | NA |
Clinical Benefit Response Rate - Arm B Expansion
Percent of participants with confirmed complete response (CR), partial response (PR) or stable disease (SD) for at least 24 weeks on study according to Response Evaluation Criteria in Solid Tumors (RECIST). Per RECIST v1.1: 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) and no new 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 and no new lesions. SD was defined as not qualifying for CR, PR, Progressive Disease (PD). (NCT01920061)
Timeframe: Baseline up to 18 months.
| Intervention | Percentage of participants (Number) |
|---|
| Arm 1: 1L Metastasic | 60.0 |
| Arm 2: 2L/3L Metastatic | 50.0 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | hr (Median) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0.517 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 0.500 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0.500 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 0.517 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 0.542 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | hr (Median) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0.500 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | NA |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0.500 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0.500 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | NA |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | hr (Median) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0.500 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 0.500 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 0.550 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 0.500 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 0.675 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 0.517 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 0.517 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
| Intervention | hr (Median) |
|---|
| Arm 1: 1L Metastasic | 0.517 |
| Arm 2: 2L/3L Metastatic | 0.500 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Docetaxel IV Infusion in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | hr (Median) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1.06 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 1.34 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 1.03 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1.02 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1.13 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | hr (Median) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 2.05 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 2.00 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 2.00 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 2.00 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 2.00 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 2.02 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 2.01 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Progression Free Survival - Arm B Expansion
"Progression free survival (PFS) defined as the time from first dose of study treatment to date of first documentation of progression or death due to any cause, whichever occurs first. PFS was calculated as first event date minus the date of first dose of study medication plus 1 . 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)." (NCT01920061)
Timeframe: Baseline up to 18 months.
| Intervention | month (Median) |
|---|
| Arm 1: 1L Metastasic | 4.8 |
| Arm 2: 2L/3L Metastatic | 8.5 |
Percentage of Participants With Objective Response - Arm C
Percentage of participants with objective response based on the assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1: 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) and no new 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 and no new lesions. (NCT01920061)
Timeframe: Baseline up to 18 months.
| Intervention | Percentage of Participants (Number) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 20.0 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 25.0 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 14.3 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 33.3 |
Percentage of Participants With Objective Response - Arm B Expansion
"Percentage of participants with objective response based on the assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Confirmed responses are those that persist on repeat imaging study at least 4 weeks after initial documentation of response.~Per RECIST v1.1: 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) and no new 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 and no new lesions." (NCT01920061)
Timeframe: Cycle 1 Day 1 up to 18 months
| Intervention | Percentage of participants (Number) |
|---|
| Arm 1: 1L Metastasic | 40.0 |
| Arm 2: 2L/3L Metastatic | 33.3 |
Percentage of Participants With Objective Response - Arm B
Percentage of participants with objective response based on the assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1: 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) and no new 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 and no new lesions. (NCT01920061)
Timeframe: Baseline up to 18 months.
| Intervention | Percentage of Participants (Number) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0.0 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 33.3 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 66.7 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 66.7 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 33.3 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 20.0 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 20.0 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | 50.0 |
Percentage of Participants With Objective Response - Arm A
Percentage of participants with objective response based on the assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Per RECIST v1.1: 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) and no new 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 and no new lesions. (NCT01920061)
Timeframe: Baseline up to 18 months.
| Intervention | Percentage of Participants (Number) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 40 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 66.7 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 20 |
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm 1: 1L Metastasic | 11340 |
| Arm 2: 2L/3L Metastatic | 10690 |
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 6455 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 9539 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 12090 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 7128 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 12420 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 4522 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 7297 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 7969 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 9548 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 13350 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 15170 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 11510 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 6703 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 8999 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6783 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 4266 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 8261 |
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 946.7 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 2451 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 2528 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1529 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1058 |
Maximum Observed Plasma Concentration (Cmax) Following Single IV Infusion Dose of Cisplatin Alone - Plasma Platinum (Arm B)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 3397 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 3950 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 3014 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 4041 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 3337 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 3474 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 3293 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 52.38 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | NA |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 33.64 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 48.10 |
Maximum Observed Plasma Concentration (Cmax) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 41.04 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 76.24 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 34.17 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 49.90 |
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 8032 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 8095 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 10380 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 11110 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 10860 |
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 6739 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | NA |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6328 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 8547 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | NA |
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 10670 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 7830 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 6273 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 9619 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | NA |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 18730 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 15000 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Maximum Observed Plasma Concentration (Cmax) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Cmax is defined as maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
| Intervention | ng/mL (Geometric Mean) |
|---|
| Arm 1: 1L Metastasic | 9027 |
| Arm 2: 2L/3L Metastatic | 14670 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
AUClast is defined as area under the curve from time zero to last quantifiable concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | NA |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 12530 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 15270 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | NA |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 18710 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 6756 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 8937 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | NA |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 14370 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 17710 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 24540 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 24480 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 9191 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 13360 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 10050 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 9493 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 10370 |
Mean Serum Biomarkers for Glucose - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This study employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | mg/dL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of prostate cancer |
|---|
| Arm A | 106.80 | 99.56 | 124.51 |
Mean Serum Biomarkers for Glucose - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This study employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | mg/dL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of head and neck cancer | In population of oesophageal carcinoma |
|---|
| Arm C | 95.07 | 97.00 | 90.68 | 103.54 |
Mean Serum Biomarkers for Glucose - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This study employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | mg/dL (Mean) |
|---|
| In population of NSCLC | In population of OC | In population of TCC | In population of TNBC |
|---|
| Arm B | 100.97 | 102.71 | 109.70 | 95.66 |
Mean Serum Biomarkers for Glucose - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | mg/dL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of prostate cancer |
|---|
| Arm A | 120.00 | 96.13 | 136.91 |
Mean Observed Score Values for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (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). 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. (NCT01920061)
Timeframe: Baseline, Day 1 and Day 8 of Cycles 1 and 2, Day 1 of Cycles 3 to 16.
| Intervention | Score on a scale (Mean) |
|---|
| Baseline | Cycle 1 Day 8 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 3 Day 1 | Cycle 4 Day 1 | Cycle 5 Day 1 | Cycle 6 Day 1 | Cycle 7 Day 1 | Cycle 8 Day 1 | Cycle 9 Day 1 | Cycle 10 Day 1 | Cycle 11 Day 1 | Cycle 12 Day 1 | Cycle 13 Day 1 | Cycle 14 Day 1 | Cycle 15 Day 1 | Cycle 16 Day 1 |
|---|
| Arm 1: 1L Metastasic | 64.58 | 50.00 | 53.12 | 50.00 | 56.25 | 45.84 | 45.00 | 55.00 | 46.67 | 51.67 | 56.25 | 66.67 | 54.17 | 62.50 | NA | NA | NA | NA |
,| Arm 2: 2L/3L Metastatic | 58.33 | 50.00 | 56.82 | 52.38 | 57.41 | 48.15 | 51.04 | 51.39 | 52.78 | 44.44 | 56.25 | 56.25 | 54.17 | 52.08 | 63.89 | 58.33 | 61.11 | 55.56 |
Mean Change From Baseline for European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) - Arm B Expansion
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (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). 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. (NCT01920061)
Timeframe: Baseline, Day 1 and Day 8 of Cycles 1 and 2, Day 1 of Cycles 3 to 16.
| Intervention | Score on a scale (Mean) |
|---|
| Cycle 1 Day 8 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 3 Day 1 | Cycle 4 Day 1 | Cycle 5 Day 1 | Cycle 6 Day 1 | Cycle 7 Day 1 | Cycle 8 Day 1 | Cycle 9 Day 1 | Cycle 10 Day 1 | Cycle 11 Day 1 | Cycle 12 Day 1 | Cycle 13 Day 1 | Cycle 14 Day 1 | Cycle 15 Day 1 | Cycle 16 Day 1 |
|---|
| Arm 1: 1L Metastasic | -16.67 | -11.46 | -14.28 | -10.42 | -14.58 | -21.67 | -11.67 | -20.00 | -15.00 | -4.16 | 5.55 | 0.01 | 8.34 | NA | NA | NA | NA |
,| Arm 2: 2L/3L Metastatic | -9.17 | -1.52 | -7.14 | 1.85 | -7.41 | -5.21 | -8.33 | 0.00 | -8.33 | -4.16 | -4.16 | -6.25 | -8.34 | 0.00 | -5.56 | -2.78 | -8.33 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
| Intervention | hr (Median) |
|---|
| Arm 1: 1L Metastasic | 0.517 |
| Arm 2: 2L/3L Metastatic | 0.600 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of PF-05212384 Alone - Plasma PF-05212384 (Arms A, B and C)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 1 Day 1 for Arms A and B; pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 14 days prior to Cycle 1 Day 1 for Arm C.
| Intervention | hr (Median) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 0.500 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 0.500 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 0.500 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 0.550 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 0.500 |
| Arm B1: 90 mg PF-05212384 + Cisplatin | 0.584 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 0.517 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | 0.500 |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 0.500 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 0.533 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 0.509 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 0.500 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 0.500 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 0.500 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 0.533 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 0.500 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | 0.533 |
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose 7 days prior to Cycle 2 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 14620 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 12690 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | NA |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 18920 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | NA |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 38850 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 27480 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Dacomitinib - Plasma PF-05212384 (Arm C)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 10870 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | NA |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 9977 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 15910 |
| Arm C4: 150 mg PF-05212384 + 30 mg Dacomitinib | NA |
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Docetaxel- Plasma PF-05212384 (Arm A)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 hours post-dose on Cycle 2 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 10420 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 15110 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 15520 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 14540 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 15890 |
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib Alone - Plasma Dacomitinib (Arm C)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau. (NCT01920061)
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 818.8 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | 1604 |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 697.0 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 1040 |
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau. (NCT01920061)
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 1069 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | NA |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 703.8 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | NA |
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Single IV Infusion Dose of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 1 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm 1: 1L Metastasic | 20180 |
| Arm 2: 2L/3L Metastatic | 24480 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Cisplatin IV Infusion in Combination With PF-05212384 - Plasma Platinum (Arm B)
AUClast is defined as area under the curve from time zero to last quantifiable concentration. (NCT01920061)
Timeframe: Pre-dose, 2, 2.5, 3, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm B1: 90 mg PF-05212384 + Cisplatin | 59390 |
| Arm B2: 110 mg PF-05212384 + Cisplatin | 62990 |
| Arm B3: 130 mg PF-05212384 + Cisplatin | NA |
| Arm B4: 150 mg PF-05212384 + Cisplatin | 56170 |
| Arm B5: 180 mg PF-05212384 + Cisplatin | 52940 |
| Arm B6: 215 mg PF-05212384 + Cisplatin | 53470 |
| Arm B7: 260 mg PF-05212384 + Cisplatin | 47500 |
| Arm B8: 310 mg PF-05212384 + Cisplatin | NA |
Area Under the Concentration-time Profile From Time 0 to Time Tau (AUCtau) Following Multiple IV Infusion Doses of PF-05212384 in Combination With Cisplatin - Plasma PF-05212384 (Arm B Expansion)
AUCtau is defined as area under the concentration-time profile from time 0 to time tau. (NCT01920061)
Timeframe: Pre-dose, 0.5, 1, 2, 4, 6, 24, 72, 96 and 168 (predose Day 8) hours post-dose on Cycle 2 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm 1: 1L Metastasic | 25250 |
| Arm 2: 2L/3L Metastatic | 31160 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Single IV Infusion Dose of Docetaxel Alone- Plasma Docetaxel (Arm A)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 1 Day 1.
| Intervention | hr (Median) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 1.12 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 1.00 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | 1.00 |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1.02 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1.05 |
Mean Serum Biomarkers for Glucose - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | mg/dL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of head and neck cancer | In population of oesophageal carcinoma |
|---|
| Arm C | 99.84 | 97.50 | 90.19 | 1.14 |
Mean Serum Biomarkers for Glucose - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as glucose as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | mg/dL (Mean) |
|---|
| In population of NSCLC | In population of OC | In population of TCC | In population of TNBC |
|---|
| Arm B | 108.11 | 143.26 | 100.71 | 108.29 |
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of HbA1c (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of prostate cancer |
|---|
| Arm A | 7.92 | 7.27 | 8.03 |
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of HbA1c (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of head and neck cancer | In population of oesophageal carcinoma |
|---|
| Arm C | 7.00 | 5.13 | 7.50 | 7.00 |
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of HbA1c (Mean) |
|---|
| In population of NSCLC | In population of OC | In population of TCC | In population of TNBC |
|---|
| Arm B | 6.65 | 7.70 | 7.65 | 7.18 |
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | Percentage of HbA1c (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of prostate cancer |
|---|
| Arm A | NA | 7.70 | 8.42 |
Mean Serum Biomarkers for Insulin - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | microunits/mL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of head and neck cancer | In population of oesophageal carcinoma |
|---|
| Arm C | 155.14 | 11.53 | 101.31 | 338.98 |
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | Percentage of HbA1c (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of head and neck cancer | In population of oesophageal carcinoma |
|---|
| Arm C | 8.39 | NA | 7.72 | 7.61 |
Mean Serum Biomarkers for Hemoglobin A1c (HbA1c) - End of Treatment
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as hemoglobin A1c (HbA1c) as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: End of treatment. Maximum duration between first and last dose: 505 days for Arm A, 414 days for Arm B, 842 days for Arm C, 728 days for Arm B Expansion.
| Intervention | Percentage of HbA1c (Mean) |
|---|
| In population of NSCLC | In population of OC | In population of TCC | In population of TNBC |
|---|
| Arm B | 6.74 | 25.10 | 7.72 | 7.72 |
Mean Serum Biomarkers for Insulin - Baseline
A phosphatidylinositol 3 kinase/mammalian target of rapamycin (PI3K/mTOR) inhibitor should disrupt the cellular uptake and metabolism of glucose. This studies employed metabolic biomarkers such as insulin as pharmacodynamics markers for dual PI3K/mTOR inhibition. (NCT01920061)
Timeframe: Baseline
| Intervention | microunits/mL (Mean) |
|---|
| In population of BC | In population of NSCLC | In population of prostate cancer |
|---|
| Arm A | 10.93 | 28.61 | 12.65 |
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast) Following Administration of Docetaxel in Combination With PF-05212384 - Plasma Docetaxel (Arm A)
AUClast is defined as area under the curve from time zero to last quantifiable concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 1.5, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | ng*hr/mL (Geometric Mean) |
|---|
| Arm A1: 90 mg PF-05212384 + Docetaxel | 2921 |
| Arm A2: 110 mg PF-05212384 + Docetaxel | 2175 |
| Arm A3: 130 mg PF-05212384 + Docetaxel | NA |
| Arm A4: 150 mg PF-05212384 + Docetaxel | 1415 |
| Arm A5: 180 mg PF-05212384 + Docetaxel | 1383 |
Percentage of Participants With BRAF and KRAS Mutations in Population of Oesophageal Carcinoma - Arm C
Biopsies were obtained at screening and after drug administration. These samples were analyzed predominantly for phosphoprotein biomarkers indicative of pathway modulation, or for genetic markers correlated to drug sensitivity (eg, emerging KRAS mutation and BRAF mutation). BRAF mutation categories included BRAF mutation status and V600E. KRAS mutation categories included GLY12ALA, GLY12ARG, GLY12ASP, GLY12CYS, GLY12SER, GLY12VAL and GLY13ASP. (NCT01920061)
Timeframe: Baseline
| Intervention | Percentage of Participants (Number) |
|---|
| BRAF - BRAF mutaion status (mutation detected) | BRAF - BRAF mutaion status (mutation not detected) | BRAF - V600E (mutation detected) | BRAF - V600E (mutation not detected) | KRAS - GLY12ALA (mutation detected) | KRAS - GLY12ALA (mutation not detected) | KRAS - GLY12ARG (mutation detected) | KRAS - GLY12ARG (mutation not detected) | KRAS - GLY12ASP (mutation detected) | KRAS - GLY12ASP (mutation not detected) | KRAS - GLY12CYS (mutation detected) | KRAS - GLY12CYS (mutation not detected) | KRAS - GLY12SER (mutation detected) | KRAS - GLY12SER (mutation not detected) | KRAS - GLY12VAL (mutation detected) | KRAS - GLY12VAL (mutation not detected) | KRAS - GLY13ASP (mutation detected) | KRAS - GLY13ASP (mutation not detected) |
|---|
| Arm C | 0 | 42.9 | 0 | 42.9 | 0 | 100.0 | 0 | 100.0 | 14.3 | 85.7 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 | 0 | 100.0 |
Time to Reach Maximum Observed Plasma Concentration (Tmax) Following Multiple Oral Doses of Dacomitinib in Combination With PF-05212384 - Plasma Dacomitinib (Arm C)
Tmax is defined as time to reach maximum observed plasma concentration. (NCT01920061)
Timeframe: Pre-dose, 1, 2, 4, 6, and 24 hours post-dose on Cycle 2 Day 1.
| Intervention | hr (Median) |
|---|
| Arm C1: 90 mg PF-05212384 + 30 mg Dacomitinib | 6.04 |
| Arm C1h: 90 mg PF-05212384 + 45 mg Dacomitinib | NA |
| Arm C2: 110 mg PF-05212384 + 30 mg Dacomitinib | 6.00 |
| Arm C3: 130 mg PF-05212384 + 30 mg Dacomitinib | 5.42 |
Change From Mean Baseline Score to Mean Score at 12 Months Post-RT in Swallow Function as Measured by the Pharyngeal Total Modified Barium Swallow Impairment Profile.
The swallow evaluation consists of a modified barium swallow study(MBS), Functional Oral Intake Scale(FOIS), and Performance Status Scale Head & Neck(PSS-HN).The 17 swallow questions are rated using a 0 to 5 point scale, with 0 meaning no impairment and 5 max impairment. 6 questions produce a total oral score; scores from 10 questions produce a total pharyngeal score; 1 question produces an esophageal score.The PAS is a validated 8-point scale that ranks the depth of the bolus entry into the airway.A score of 1 indicates no airway entrance;score of 6+ indicate bolus passage past the vocal folds (aspiration).FOIS ranges from 1(nothing by mouth) to 7(total oral diet with no restrictions).PSS-H&N has 3 components:eating in public(0=always eat alone to 100=no restriction), understandability of speech(0=never understandable, score 100=always understandable), and normalcy of diet(score 0=tube fed to 100=full diet).These scores are summed and normalized to a 0 to 100 scale where 100 is best. (NCT01932697)
Timeframe: 12 months
| Intervention | score on a scale (Mean) |
|---|
| Baseline time point | 12 month time point |
|---|
| All Patients | 5.57 | 4.48 |
Functional Assessment of Cancer Therapy Head and Neck (FACT H& N) (Version 4)
The FACT-H&N is a multidimensional, self-report QOL instrument specifically designed for use with head and neck cancer patients. It consists of 27 core items which assess patient function in four domains: Physical, Social/Family, Emotional, and Functional well-being, in addition to 12 site specific items to assess for head and neck related symptoms. Each item is rated on a 0 to 4 type scale where 4 is favorable and 0 unfavorable, and then combined to produce subscale scores for each domain, as well as a global QOL score- with possible score range from 0 to 156. Higher scores represent better QOL. (NCT01932697)
Timeframe: 1 year
| Intervention | score on a scale (Mean) |
|---|
| Baseline | 12 months |
|---|
| All Patients | 117.2 | 127.2 |
Incidence of Grade 3 or Higher Mucositis Oral
The overall percentage of patients experiencing grade 3 or higher mucositis oral graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 are reported below. (NCT01932697)
Timeframe: 4 months post-hyperfractionated radiation therapy
| Intervention | percentage of patients (Number) |
|---|
| Cohort A (Intermediate Risk) | 8.3 |
| Cohort B (Extranodal Extension) | 4.7 |
2-year Loco-regional Tumor Control (LRC) Rate
The 2-year loco-regional tumor control (LRC) rate (percentage) is defined as the percentage of patients with no local/regional recurrence or death 2 years after study registration. (NCT01932697)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| Cohort A (Intermediate Risk) | 100 |
| Cohort B (Extranodal Extension) | 93 |
| Overall (Cohort A + Cohort B) | 96.2 |
2-year Overall Survival (OS) Rate
The distribution of OS will be estimated using the method of Kaplan-Meier. (NCT01932697)
Timeframe: 2 years
| Intervention | percentage of patients (Number) |
|---|
| Cohort A | 100 |
| Cohort B | 97.7 |
2-year Progression-free Survival (PFS)
The distribution of PFS will be estimated using the method of Kaplan-Meier. (NCT01932697)
Timeframe: From registration to the first of either disease recurrence or death, assessed up to 2 years
| Intervention | percentage of patients (Number) |
|---|
| Cohort A (Intermediate Risk) | 97.2 |
| Cohort B (Extranodal Extension) | 86.0 |
European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35)
QOL was measured by the European Organization for Research and Treatment for Cancer QOL Questionnaire for Head and Neck Cancer Module 35 (EORTC-QLQ HN35) at baseline and at 1-year post-treatment. Each question scores 0-4, with 0 being favorable and 4 being unfavorable. The average total score at baseline and average total score at 12 months post-RT is reported. The max total score possible is 140(Unfavorable) and the minimum total score possible is 0(Favorable). An increase in score indicates a greater quality of life A paired t-test compares the scores at these two timepoints. (NCT01932697)
Timeframe: 1 year post-treatment
| Intervention | score on a scale (Mean) |
|---|
| Cohort A (Intermediate Risk) | 106.3 |
| Cohort B (Extranodal Extension) | 111.4 |
EuroQol Five-dimensional Instrument (EQ-5D-3L)
QOL was measured by the three-level version of the EuroQol five-dimensional instrument (EQ-5D-3L) at baseline and 1-year post-treatment. This consisted of 5 questions, each score 0 to 3 points with 3 being unfavorable and 0 being favorable. The total possible score per patient per time point is 15 and a minimum score of 0(favorable). The change in average total score at baseline and 12 months post-RT is reported. A paired t-test compares the scores at these two time points. A higher score indicates greater impairment. (NCT01932697)
Timeframe: 1 year post-treatment
| Intervention | score on a scale (Mean) |
|---|
| Cohort A (Intermediate Risk) | 6.3 |
| Cohort B (Extranodal Extension) | 5.5 |
Symptom Improvement Rate Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
The symptom improvement rate will be defined as the number (%) of patients with two consecutive assessments at least 18 days apart (ie 21 days allowing a visit window of 3 days) which showed a clinically meaningful improvement in symptoms from baseline (defined as a decrease in the ASBI from baseline ≥10). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index. (NCT01933932)
Timeframe: Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)
| Intervention | Number of patients with improvements (Number) |
|---|
| Selumetinib + Docetaxel | 49 |
| Placebo + Docetaxel | 46 |
Duration of Response (DoR)
Duration of response is defined as the time from the date of first documented response until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression) (NCT01933932)
Timeframe: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
| Intervention | Days (Median) |
|---|
| Selumetinib + Docetaxel | 88.0 |
| Placebo + Docetaxel | 136.0 |
Overall Survival (OS)
Overall Survival is defined as the time from the date of randomisation until death due to any cause. (NCT01933932)
Timeframe: Measured at baseline until date of death due to any cause. Estimated final completion : approximately 3.5 years after FSI
| Intervention | Months (Median) |
|---|
| Selumetinib + Docetaxel | 8.7 |
| Placebo + Docetaxel | 7.9 |
Time to Symptom Progression Using Average Symptom Burden Index (ASBI) of the Lung Cancer Symptom Scale (LCSS)
Time to symptom progression will be defined as the time from randomization until the date of first clinically meaningful symptom deterioration (defined as an increase in the ASBI from baseline ≥10), or death (by any cause). LCSS-Lung Cancer Symptom Scale; ASBI-Average symptom burden index. (NCT01933932)
Timeframe: Measured from date of randomisation until 30 days post treatment discontinuation or 30 days post progression (if study treatment is discontinued before progression). Estimated final completion : approximately 3 years after first subject in (FSI)
| Intervention | Months (Median) |
|---|
| Selumetinib + Docetaxel | 1.6 |
| Placebo + Docetaxel | 1.3 |
Progression-Free Survival (PFS)
Progression free survival is defined as the time from randomisation until the date of objective disease progression (RECIST 1.1) or death (by any cause in the absence of progression) (NCT01933932)
Timeframe: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
| Intervention | Months (Median) |
|---|
| Selumetinib + Docetaxel | 3.9 |
| Placebo + Docetaxel | 2.8 |
Objective Response Rate (ORR)
ORR is defined as the number (%) of subjects with at least one overall visit response of complete response (CR) or partial response (PR). Per RECIST v1.1 for target lesions and assessed by CT/MRI: CR - disappearance of all target lesions; PR - >=30% decrease in the sum of the longest diameter of target lesion. (Non-target lesion and new lesion results are also taken into account for the overall visit result) (NCT01933932)
Timeframe: Measured at baseline until the date of first documented objective disease progression. Estimated final completion : approximately 3 years after first subject in (FSI)
| Intervention | Number of responders (Number) |
|---|
| Selumetinib + Docetaxel | 51 |
| Placebo + Docetaxel | 35 |
Percentage of Participants With Event (Local, Regional or Distant Recurrence, Contralateral Breast Cancer or Death) Using Mammography
A participant was considered as disease free if the participant was free from local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Percentage of participants with event at the cut off date were reported. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years])
| Intervention | Percentage of Participants (Number) |
|---|
| Trastuzumab (Vial): Adjuvant | 18.5 |
| Trastuzumab (Vial): Neoadjuvant | 33.3 |
| Trastuzumab (SID): Adjuvant | 6.6 |
| Trastuzumab (SID): Neoadjuvant | 11.1 |
Percentage of Participants by Response to Patient Satisfaction Questionnaire (PSQ)
"Participants were asked the following 5 questions: (1) Following the first injection given by the physician/nurse and training on how to use the SID, I felt comfortable injecting the study drug by myself; (2) The SID was convenient and easy to use; (3) I am confident giving myself an injection in the thigh with the SID; (4) Taking all things into account, I find self-administration using the SID satisfactory; (5) If given the opportunity, I would choose to continue self-injecting the study drug using the SID at home. Response to each question was recorded as either of the following options: Unknown, Strongly Disagree, Disagree, Unsure, Agree, Strongly Agree. Percentage of participants who provided responses to above questions was reported. Data for this outcome measure were analyzed and reported only for Trastuzumab (SID) arm." (NCT01940497)
Timeframe: After at least 14 cycles (1 cycle = 21 days; maximum up to 1 year)
| Intervention | Percentage of Participants (Number) |
|---|
| Comfortable: Unknown | Comfortable: Strongly Disagree | Comfortable: Disagree | Comfortable: Unsure | Comfortable: Agree | Comfortable: Strongly Agree | Convenient: Unknown | Convenient: Strongly Disagree | Convenient: Disagree | Convenient: Unsure | Convenient: Agree | Convenient: Strongly Agree | Confident: Unknown | Confident: Strongly Disagree | Confident: Disagree | Confident: Unsure | Confident: Agree | Confident: Strongly Agree | Satisfactory: Unknown | Satisfactory: Strongly Disagree | Satisfactory: Disagree | Satisfactory: Unsure | Satisfactory: Agree | Satisfactory: Strongly Agree | Would continue: Unknown | Would continue: Strongly Disagree | Would continue: Disagree | Would continue: Unsure | Would continue: Agree | Would continue: Strongly Agree |
|---|
| Trastuzumab (SID) | 0.0 | 0.0 | 0.0 | 6.7 | 40 | 53.3 | 0.0 | 0.0 | 0.0 | 6.7 | 33.3 | 60 | 0.0 | 0.0 | 0.0 | 6.7 | 40.0 | 53.3 | 0.0 | 0.0 | 0.0 | 6.7 | 33.3 | 60 | 0.0 | 0.0 | 13.3 | 6.7 | 20 | 60 |
Duration of Treatment With Trastuzumab
Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up last dose of trastuzumab (up to approximately 1 year)
| Intervention | days (Mean) |
|---|
| Trastuzumab (Vial): Adjuvant | 346 |
| Trastuzumab (Vial): Neoadjuvant | 352.2 |
| Trastuzumab (SID): Adjuvant | 340.1 |
| Trastuzumab (SID): Neoadjuvant | 351.9 |
Disease-Free Survival (DFS) Using Mammography
DFS was defined as the time from the first treatment to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first). Kaplan-Meier estimates were used for analysis. Participants who were disease-free were censored at the data cut off date. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up to local, regional or distant recurrence, contralateral breast cancer or death due to any cause (whichever occurred first [up to approximately 4.5 years])
| Intervention | Months (Median) |
|---|
| Trastuzumab (Vial): Adjuvant | NA |
| Trastuzumab (Vial): Neoadjuvant | NA |
| Trastuzumab (SID): Adjuvant | NA |
| Trastuzumab (SID): Neoadjuvant | NA |
Actual Dose of Trastuzumab Administered
Actual dose (mg) administered = (sum over all cycles of actual dose received [mg] divided by number of cycles). Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up last dose of trastuzumab (up to approximately 1 year)
| Intervention | mg (Mean) |
|---|
| Trastuzumab (Vial): Adjuvant | 599.7 |
| Trastuzumab (Vial): Neoadjuvant | 600.00 |
| Trastuzumab (SID): Adjuvant | 593.3 |
| Trastuzumab (SID): Neoadjuvant | 595.9 |
Percentage of Health Care Professionals (HCPs) by Response to Health Care Professional Questionnaire (HCPQ)
Percentage of HCPs providing responses to various questions related to overall ease of study drug administration was reported in different categories, where categories indicate all possible responses to such questions. (NCT01940497)
Timeframe: After at least 4 participants completed 5 cycles of adjuvant treatment (1 cycle = 21 days; maximum up to 1 year)
| Intervention | Percentage of HCPs (Number) |
|---|
| Specialization: Oncologist | Specialization: Specialist nurse | Specialization: Other | Specialization: Missing | Personally administered/supervised: Always | Personally administered/supervised: Sometimes | Personally administered/supervised: Never | If 'Never', who administered: Specialist nurse | Syringe prepared at: Pharmacy | Syringe prepared at: Oncology ward | Syringe prepared at: Missing | Time to fill syringe: less than (<) 5 minutes | Time to fill syringe: 6-10 minutes | Time to fill syringe: 11-15 minutes | Time to fill syringe: Unknown | Total time for vial administration: <3 minutes | Total time for vial administration: <5 minutes | Total time for vial administration: 6-15 minutes | Time to prepare SID: <5 minutes | Time to prepare SID: 6-10 minutes | Time to prepare SID: 11-15 minutes | Time to prepare SID: 16-20 minutes | Time to prepare SID: >20 minutes | Total time for SID administration: <3 minutes | Total time for SID administration: <5 minutes | Total time for SID administration: 6-15 minutes | Injection site: Irritation: A lot | Injection site: Irritation: A few | Injection site: Irritation: None | Injection site: Bruising: A few | Injection site: Bruising: None | Injection site: Infection: None | Fever,shivering,flu-like,rash,swelling:A few | Fever,shivering,flu-like,rash,swelling:None | Time at hospital for administration: <2 hours | Time at hospital for administration: >2, <3 hours | Time at hospital for administration: >3, <4 hours | Time at hospital for administration: >4 hours | Time at hospital for administration: Missing | Anxiety to participants: None | Anxiety to participants: A fair amount | Ease of vial administration: None | Ease of vial administration: A fair amount | Ease of vial administration: A lot | Subcutaneous route may simplify management: Yes | Subcutaneous route may simplify management: No | Would recommend SID to intravenous route: Yes | Would recommend SID to intravenous route: No | Would recommend subcutaneous route to medics: Yes | Would recommend subcutaneous route to medics: No | Would recommend subcutaneous to medics:Missing | Convenience of using SID by participants: Yes | Convenience of using SID by participants: No | Convenience of using SID by participants: Missing |
|---|
| HCPs: Trastuzumab (SID) | 16.0 | 76.0 | 8.0 | 0.0 | 48.0 | 48.0 | 4.0 | 4.0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 72.0 | 14.0 | 4.0 | 2.0 | 8.0 | 26.0 | 30.0 | 44.0 | 4.0 | 36.0 | 60.0 | 10.0 | 90.0 | 100.0 | 14.0 | 86.0 | 44.0 | 34.0 | 12.0 | 10.0 | 0.0 | 90.0 | 10.0 | NA | NA | NA | 100.0 | 0.0 | 96.0 | 4.0 | 90.0 | 8.0 | 2.0 | 96.0 | 4.0 | 0.0 |
,| HCPs: Trastuzumab (Vial) | 17.3 | 69.2 | 11.5 | 1.9 | 40.4 | 51.9 | 7.7 | 7.7 | 55.8 | 40.4 | 3.8 | 67.3 | 13.5 | 5.8 | 13.5 | 1.9 | 59.6 | 38.5 | NA | NA | NA | NA | NA | NA | NA | NA | 1.9 | 46.2 | 51.9 | 7.7 | 92.3 | 100.0 | 15.4 | 84.6 | 44.2 | 23.1 | 23.1 | 7.7 | 1.9 | 82.7 | 17.3 | 5.8 | 38.5 | 55.8 | 94.2 | 5.8 | 96.2 | 3.8 | 100.0 | 0.0 | 0.0 | 94.2 | 0.0 | 5.8 |
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. TEAEs were the AEs occurring from starting on the day of or after first administration of trastuzumab and within 28 days after last dose of trastuzumab. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up to 28 days after last dose of trastuzumab (up to approximately 1 year)
| Intervention | Percentage of Participants (Number) |
|---|
| Trastuzumab (Vial): Adjuvant | 98.9 |
| Trastuzumab (Vial): Neoadjuvant | 100.0 |
| Trastuzumab (SID): Adjuvant | 89.1 |
| Trastuzumab (SID): Neoadjuvant | 95.2 |
Percentage of Participants With Pathological Complete Response (pCR) (Neoadjuvant Groups Only) Using Mammography
In the neoadjuvant setting, the activity of two sequential drug regimens, doxorubicin-containing chemotherapy followed by paclitaxel or docetaxel chemotherapy in combination with trastuzumab, was assessed as the percentage of participants with pCR in breast and nodes using mammography. pCR was defined as the absence of histological evidence of invasive breast cancer cells in the tissue specimen removed from the breast after preoperative treatment. Data for this outcome measure were analyzed and reported only for neoadjuvant groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up to 24 weeks
| Intervention | Percentage of Participants (Number) |
|---|
| Trastuzumab (Vial): Neoadjuvant | 40.9 |
| Trastuzumab (SID): Neoadjuvant | 15.8 |
Percentage of Participants Who Received Concomitant Medications
(NCT01940497)
Timeframe: Screening (Day -28 to -1) up to 2.5 years
| Intervention | Percentage of Participants (Number) |
|---|
| Trastuzumab (Vial) | 100 |
| Trastuzumab (SID) | 100 |
Percentage of Participants Who Died
Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up to death due to any cause (up to approximately 4.5 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Trastuzumab (Vial): Adjuvant | 5.2 |
| Trastuzumab (Vial): Neoadjuvant | 4.5 |
| Trastuzumab (SID): Adjuvant | 0.0 |
| Trastuzumab (SID): Neoadjuvant | 5.26 |
Overall Survival (OS)
Overall survival was defined as the time from the first treatment to death from any cause. Kaplan-Meier estimates were used for analysis. Participants who did not die were censored on the date they were last known to be alive. Data for this outcome measure were analyzed and reported by adjuvant versus neoadjuvant chemotherapy groups within each treatment arm. (NCT01940497)
Timeframe: Day 1 up to death due to any cause (up to approximately 4.5 years)
| Intervention | Months (Median) |
|---|
| Trastuzumab (Vial): Adjuvant | NA |
| Trastuzumab (Vial): Neoadjuvant | NA |
| Trastuzumab (SID): Adjuvant | NA |
| Trastuzumab (SID): Neoadjuvant | NA |
Progression-free Survival Rate at Six Months (PFS6)
The rate estimate of the percentage of patients who are alive and progression-free at 24 weeks (~6 months) after randomization. Progession disease 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 also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. (NCT01951157)
Timeframe: At month six after patient inclusion
| Intervention | percentage of participants (Number) |
|---|
| A - Docetaxel | 18.2 |
| B - Lurbinectedin (PM01183) | 16.7 |
| C - Gemcitabine + Lurbinectedin (PM01183) | 17.5 |
Progression-free Survival Rate at Four Months (PFS4)
The rate estimate of the percentage of patients who are alive and progression-free at 16 weeks (~4 months) after randomization. Progession disease 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 also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. (NCT01951157)
Timeframe: At month four after patient inclusion
| Intervention | percentage of participants (Number) |
|---|
| A - Docetaxel | 27.3 |
| B - Lurbinectedin (PM01183) | 15.8 |
| C - Gemcitabine + Lurbinectedin (PM01183) | 26.1 |
Progression-free Survival
PFS, progression-free survival Progression-free survival (PFS), defined as the time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation. Progession disease 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 also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. (NCT01951157)
Timeframe: Time from the date of randomization to the date of PD, death (of any cause), or last tumor evaluation, whichever came first, assessed up to 3 years
| Intervention | months (Median) |
|---|
| A - Docetaxel | 3.1 |
| B - Lurbinectedin (PM01183) | 1.9 |
| C - Gemcitabine + Lurbinectedin (PM01183) | 3.3 |
Overall Survival (OS)
Overall survival (OS) will be defined as time from the date of first infusion to the date of death or last contact (NCT01951157)
Timeframe: From the date of first infusion to the date of death or last contact, up to 12 months after last patient inclusion
| Intervention | months (Median) |
|---|
| A - Docetaxel | 9.4 |
| B - Lurbinectedin (PM01183) | 5.5 |
| C - Gemcitabine + Lurbinectedin (PM01183) | 7.2 |
Overall Response Rate
"Overall response rate (ORR) was defined as the percentage of patients with a response, either CR or PR, according to RECIST v.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." (NCT01951157)
Timeframe: Time from the date of randomization until 30±7 days after the last treatment infusion, assessed up to 3 years
| Intervention | percentage of participants (Number) |
|---|
| A - Docetaxel | 9.1 |
| B - Lurbinectedin (PM01183) | 0 |
| C - Gemcitabine + Lurbinectedin (PM01183) | 17.4 |
Duration of Response
"Duration of response (DR) was defined as the time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented.~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." (NCT01951157)
Timeframe: The time from the date when the response criteria (PR or CR, whichever was reached first) were fulfilled, to the first date when PD, recurrence or death was documented, up to 3 years
| Intervention | months (Median) |
|---|
| A - Docetaxel | 1.2 |
| C - Gemcitabine + Lurbinectedin (PM01183) | 6.1 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1P (HER2 Positive) | 4 |
| Cohort 1T (HER2 Positive) | 6 |
| Cohort II (HER2 Negative) | 3 |
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 7 - 15 points considered to be a clinically meaningful detioration to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1). (NCT01966471)
Timeframe: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
| Intervention | Units on a Scale (Mean) |
|---|
| Baseline: Appetite Loss | Change at Cycle 1: Appetite Loss | Change at Cycle 2: Appetite Loss | Change at Cycle 3: Appetite Loss | Change at Cycle 4: Appetite Loss | Change at Cycle 5: Appetite Loss | Change at Cycle 9: Appetite Loss | Change at Cycle 14: Appetite Loss | Change at EoT: Appetite Loss | Change at FU Month 6: Appetite Loss | Change at FU Month 12: Appetite Loss | Change at FU Month 18: Appetite Loss | Baseline: Constipation | Change at Cycle 1: Constipation | Change at Cycle 2: Constipation | Change at Cycle 3: Constipation | Change at Cycle 4: Constipation | Change at Cycle 5: Constipation | Change at Cycle 9: Constipation | Change at Cycle 14: Constipation | Change at EoT: Constipation | Change at FU Month 6: Constipation | Change at FU Month 12: Constipation | Change at FU Month 18: Constipation | Baseline: Diarrhea | Change at Cycle 1: Diarrhea | Change at Cycle 2: Diarrhea | Change at Cycle 3: Diarrhea | Change at Cycle 4: Diarrhea | Change at Cycle 5: Diarrhea | Change at Cycle 9: Diarrhea | Change at Cycle 14: Diarrhea | Change at EoT: Diarrhea | Change at FU Month 6: Diarrhea | Change at FU Month 12: Diarrhea | Change at FU Month 18: Diarrhea | Baseline: Dyspnea | Change at Cycle 1: Dyspnea | Change at Cycle 2: Dyspnea | Change at Cycle 3: Dyspnea | Change at Cycle 4: Dyspnea | Change at Cycle 5: Dyspnea | Change at Cycle 9: Dyspnea | Change at Cycle 14: Dyspnea | Change at EoT: Dyspnea | Change at FU Month 6: Dyspnea | Change at FU Month 12: Dyspnea | Change at FU Month 18: Dyspnea | Baseline: Fatigue | Change at Cycle 1: Fatigue | Change at Cycle 2: Fatigue | Change at Cycle 3: Fatigue | Change at Cycle 4: Fatigue | Change at Cycle 5: Fatigue | Change at Cycle 9: Fatigue | Change at Cycle 14: Fatigue | Change at EoT: Fatigue | Change at FU Month 6: Fatigue | Change at FU Month 12: Fatigue | Change at FU Month 18: Fatigue | Baseline: Financial Difficulties | Change at Cycle 1: Financial Difficulties | Change at Cycle 2: Financial Difficulties | Change at Cycle 3: Financial Difficulties | Change at Cycle 4: Financial Difficulties | Change at Cycle 5: Financial Difficulties | Change at Cycle 9: Financial Difficulties | Change at Cycle 14: Financial Difficulties | Change at EoT: Financial Difficulties | Change at FU Month 6: Financial Difficulties | Change at FU Month 12: Financial Difficulties | Change at FU Month 18: Financial Difficulties | Baseline: Insomnia | Change at Cycle 1: Insomnia | Change at Cycle 2: Insomnia | Change at Cycle 3: Insomnia | Change at Cycle 4: Insomnia | Change at Cycle 5: Insomnia | Change at Cycle 9: Insomnia | Change at Cycle 14: Insomnia | Change at EoT: Insomnia | Change at FU Month 6: Insomnia | Change at FU Month 12: Insomnia | Change at FU Month 18: Insomnia | Baseline: Nausea/Vomiting | Change at Cycle 1: Nausea/Vomiting | Change at Cycle 2: Nausea/Vomiting | Change at Cycle 3: Nausea/Vomiting | Change at Cycle 4: Nausea/Vomiting | Change at Cycle 5: Nausea/Vomiting | Change at Cycle 9: Nausea/Vomiting | Change at Cycle 14: Nausea/Vomiting | Change at EoT: Nausea/Vomiting | Change at FU Month 6: Nausea/Vomiting | Change at FU Month 12: Nausea/Vomiting | Change at FU Month 18: Nausea/Vomiting | Baseline: Pain | Change at Cycle 1: Pain | Change at Cycle 2: Pain | Change at Cycle 3: Pain | Change at Cycle 4: Pain | Change at Cycle 5: Pain | Change at Cycle 9: Pain | Change at Cycle 14: Pain | Change at EoT: Pain | Change at FU Month 6: Pain | Change at FU Month 12: Pain | Change at FU Month 18: Pain | Baseline: Cognitive Functioning | Change at Cycle 1: Cognitive Functioning | Change at Cycle 2: Cognitive Functioning | Change at Cycle 3: Cognitive Functioning | Change at Cycle 4: Cognitive Functioning | Change at Cycle 5: Cognitive Functioning | Change at Cycle 9: Cognitive Functioning | Change at Cycle 14: Cognitive Functioning | Change at EoT: Cognitive Functioning | Change at FU Month 6: Cognitive Functioning | Change at FU Month 12: Cognitive Functioning | Change at FU Month 18: Cognitive Functioning | Baseline: Emotional Functioning | Change at Cycle 1: Emotional Functioning | Change at Cycle 2: Emotional Functioning | Change at Cycle 3: Emotional Functioning | Change at Cycle 4: Emotional Functioning | Change at Cycle 5: Emotional Functioning | Change at Cycle 9: Emotional Functioning | Change at Cycle 14: Emotional Functioning | Change at EoT: Emotional Functioning | Change at FU Month 6: Emotional Functioning | Change at FU Month 12: Emotional Functioning | Change at FU Month 18: Emotional Functioning | Baseline: Physical Functioning | Change at Cycle 1: Physical Functioning | Change at Cycle 2: Physical Functioning | Change at Cycle 3: Physical Functioning | Change at Cycle 4: Physical Functioning | Change at Cycle 5: Physical Functioning | Change at Cycle 9: Physical Functioning | Change at Cycle 14: Physical Functioning | Change at EoT: Physical Functioning | Change at FU Month 6: Physical Functioning | Change at FU Month 12: Physical Functioning | Change at FU Month 18: Physical Functioning | Baseline: Role Functioning | Change at Cycle 1: Role Functioning | Change at Cycle 2: Role Functioning | Change at Cycle 3: Role Functioning | Change at Cycle 4: Role Functioning | Change at Cycle 5: Role Functioning | Change at Cycle 9: Role Functioning | Change at Cycle 14: Role Functioning | Change at EoT: Role Functioning | Change at FU Month 6: Role Functioning | Change at FU Month 12: Role Functioning | Change at FU Month 18: Role Functioning | Baseline: Social Functioning | Change at Cycle 1: Social Functioning | Change at Cycle 2: Social Functioning | Change at Cycle 3: Social Functioning | Change at Cycle 4: Social Functioning | Change at Cycle 5: Social Functioning | Change at Cycle 9: Social Functioning | Change at Cycle 14: Social Functioning | Change at EoT: Social Functioning | Change at FU Month 6: Social Functioning | Change at FU Month 12: Social Functioning | Change at FU Month 18: Social Functioning | Baseline: Global Health Status | Change at Cycle 1: Global Health Status | Change at Cycle 2: Global Health Status | Change at Cycle 3: Global Health Status | Change at Cycle 4: Global Health Status | Change at Cycle 5: Global Health Status | Change at Cycle 9: Global Health Status | Change at Cycle 14: Global Health Status | Change at EoT: Global Health Status | Change at FU Month 6: Global Health Status | Change at FU Month 12: Global Health Status | Change at FU Month 18: Global Health Status |
|---|
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 7.6 | 10.8 | 13.1 | 10.3 | 9.4 | 9.0 | 8.2 | 6.4 | 5.6 | -2.4 | -2.3 | -16.7 | 9.0 | 8.0 | 0.9 | 0.2 | -0.6 | -0.4 | 3.3 | 4.2 | 4.7 | 1.5 | 2.0 | 0.0 | 4.7 | 4.2 | 16.0 | 11.3 | 10.3 | 8.8 | 4.7 | 5.1 | 3.0 | -1.1 | 0.0 | -16.7 | 6.2 | 9.2 | 7.4 | 6.5 | 5.9 | 5.6 | 7.5 | 8.1 | 8.8 | 5.3 | 5.8 | -16.7 | 20.6 | 14.4 | 11.2 | 8.7 | 8.2 | 8.4 | 9.8 | 10.6 | 9.3 | 3.1 | 1.8 | -5.6 | 19.9 | 0.3 | -0.6 | -0.4 | -0.2 | 0.7 | -0.5 | -1.0 | -1.7 | -5.2 | -6.8 | 0.0 | 24.9 | 1.8 | 0.4 | -0.1 | 1.1 | 1.1 | 1.1 | 2.7 | 0.9 | -2.3 | -2.9 | -16.7 | 2.3 | 10.5 | 7.5 | 5.2 | 3.7 | 3.2 | 2.8 | 3.0 | 1.7 | 0.1 | 0.6 | -8.3 | 16.4 | 1.1 | 2.8 | 2.5 | 3.1 | 3.8 | 3.9 | 5.7 | 5.1 | 1.4 | 0.5 | -25.0 | 88.7 | -6.9 | -6.8 | -6.4 | -6.9 | -7.3 | -7.6 | -8.1 | -8.4 | -6.1 | -6.0 | 16.7 | 75.7 | 0.0 | 1.6 | 2.2 | 2.8 | 2.6 | 2.9 | 2.5 | 3.1 | 6.1 | 6.5 | 12.5 | 89.1 | -5.9 | -4.8 | -4.1 | -3.5 | -3.5 | -3.8 | -4.2 | -4.9 | -1.6 | -0.8 | 13.3 | 83.4 | -5.7 | -5.5 | -2.7 | -3.2 | -3.5 | -3.2 | -4.3 | -3.5 | 2.4 | 3.7 | 8.3 | 83.2 | -5.3 | -4.1 | -3.3 | -3.2 | -2.6 | -3.4 | -2.4 | -1.6 | 4.0 | 6.4 | 33.3 | 73.9 | -7.2 | -7.1 | -5.2 | -5.5 | -5.8 | -6.4 | -6.3 | -4.9 | 0.3 | 1.2 | 16.7 |
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) From Baseline Over Time
LVEF was assessed using either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans. (NCT01966471)
Timeframe: First participant randomized up to approximately 7.5 years.
| Intervention | Participants (Count of Participants) |
|---|
| Decrease from baseline <10 Ejection Fraction (EF) points | Absolute value >= 50% and decrease from baseline >= 10 EF points | Absolute value < 50% and decrease from baseline >= 10 EF points | Absolute value < 50% and decrease from baseline >= 15 EF points |
|---|
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 522 | 245 | 35 | 28 |
,| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 506 | 254 | 71 | 61 |
Time to Clinically Meaningful Deterioration in the Global Health Status/ Quality of Life and Functional (Physical, Role, and Cognitive) Subscales of the QLQ-C30 From First HER2-Targeted Treatment
The time to clinically meaningful deterioration in the global health status/Quality of life and Functional (Physical, Role, and Cognitive) subscales of the the QLQ-C30 was assessed from the time of the HER2-Targeted treatment to the worsening in the respective scales. Clinically meaningful deterioration is defined as a decrease in score of 10 points in Physical functioning and HRQoL; decrease of 7 points in Cognitive functioning, and decrease of 14 points in Role functioning. (NCT01966471)
Timeframe: From start of HER-2 targeted treatment up to 18 months after treatment discontinuation. The median time to clinically meaningful deterioration was assessed based on the data collection described above.
| Intervention | months (Median) |
|---|
| GHS/QoL Score | Physical Function | Role Function | Cognitive Function |
|---|
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 13.57 | NA | 9.92 | 9.46 |
,| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 2.73 | 25.53 | 2.23 | 5.49 |
Distant Recurrence-Free Interval (DRFI)
DRFI was defined as time between randomization and first occurrence of distant breast cancer recurrence. (NCT01966471)
Timeframe: Baseline up to approximately 70 months
| Intervention | Percent Probability (Number) |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 95.23 |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 94.91 |
Invasive Disease-Free Survival (IDFS) in the Node-Positive Subpopulation
IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year IDFS event-free rate per randomized treatment arms in the ITT population was estimated using the Kaplan-Meier method and estimated the probability of a participant being event-free after 3 years after randomization. (NCT01966471)
Timeframe: Last participant randomized to data cut-off date of 27 November 2019 (approximately 70 months). The 3 year IDFS event-free rate was assessed based on the data collected for each participant considering the cut-off date mentioned above.
| Intervention | Percent Probability (Number) |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 94.10 |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 92.75 |
IDFS Plus Second Primary Non-Breast Cancer
IDFS including second primary non-breast cancer was defined the same way as IDFS for the primary endpoint but including second primary non breast invasive cancer as an event (with the exception of non-melanoma skin cancers and carcinoma in situ (CIS) of any site). (NCT01966471)
Timeframe: Baseline up to approximately 70 months
| Intervention | Percent Probability (Number) |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 93.43 |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 92.26 |
Disease-Free Survival (DFS)
DFS was defined as time between randomization and first occurrence of IDFS, second primary non-breast cancer and contralateral or ipsilateral ductal carcinoma in situ (DCIS). (NCT01966471)
Timeframe: Baseline up to approximately 70 months
| Intervention | Percent Probability (Number) |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 93.32 |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 92.04 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. (NCT01966471)
Timeframe: First participant randomized up to approximately 7.5 years
| Intervention | Percent Probability (Number) |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 96.03 |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 94.86 |
Invasive Disease-Free Survival (IDFS) in the Overall Population
IDFS event was defined as the time from randomization until the date of first occurrence of one of the following: Ipsilateral invasive breast tumor recurrence (an invasive breast cancer [bc] involving the same breast parenchyma as the original primary lesion); Ipsilateral local-regional invasive bc recurrence (an invasive bc in the axilla, regional lymph nodes, chest wall, and/or skin of the ipsilateral breast); Contralateral or ipsilateral second primary invasive bc; Distant recurrence (evidence of bc in any anatomic site [other than the three sites mentioned above]) that has either been histologically confirmed or clinically/radiographically diagnosed as recurrent invasive bc; Death attributable to any cause, including bc, non-bc, or unknown cause. 3-year 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 randomization. (NCT01966471)
Timeframe: First participant randomized up to approximately 7.5 years
| Intervention | Percent Probability (Number) |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 94.22 |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 93.06 |
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Score
The EORTC QLQ-C30 included global health status, functional scales (physical, role, emotional, cognitive, and social), symptom scales (fatigue, nausea/vomiting, and pain) and single items (dyspnoea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Most questions used a 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to 0 - 100 scale, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 7 - 15 points considered to be a clinically meaningful detioration to participants. A positive value means an increase, while a negative value means a decrease, in score at the indicated time-point relative to the score at baseline (Cycle 1, Day 1). (NCT01966471)
Timeframe: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
| Intervention | Units on a Scale (Mean) |
|---|
| Baseline: Appetite Loss | Change at Cycle 1: Appetite Loss | Change at Cycle 2: Appetite Loss | Change at Cycle 3: Appetite Loss | Change at Cycle 4: Appetite Loss | Change at Cycle 5: Appetite Loss | Change at Cycle 9: Appetite Loss | Change at Cycle 14: Appetite Loss | Change at EoT: Appetite Loss | Change at FU Month 6: Appetite Loss | Change at FU Month 12: Appetite Loss | Baseline: Constipation | Change at Cycle 1: Constipation | Change at Cycle 2: Constipation | Change at Cycle 3: Constipation | Change at Cycle 4: Constipation | Change at Cycle 5: Constipation | Change at Cycle 9: Constipation | Change at Cycle 14: Constipation | Change at EoT: Constipation | Change at FU Month 6: Constipation | Change at FU Month 12: Constipation | Baseline: Diarrhea | Change at Cycle 1: Diarrhea | Change at Cycle 2: Diarrhea | Change at Cycle 3: Diarrhea | Change at Cycle 4: Diarrhea | Change at Cycle 5: Diarrhea | Change at Cycle 9: Diarrhea | Change at Cycle 14: Diarrhea | Change at EoT: Diarrhea | Change at FU Month 6: Diarrhea | Change at FU Month 12: Diarrhea | Baseline: Dyspnea | Change at Cycle 1: Dyspnea | Change at Cycle 2: Dyspnea | Change at Cycle 3: Dyspnea | Change at Cycle 4: Dyspnea | Change at Cycle 5: Dyspnea | Change at Cycle 9: Dyspnea | Change at Cycle 14: Dyspnea | Change at EoT: Dyspnea | Change at FU Month 6: Dyspnea | Change at FU Month 12: Dyspnea | Baseline: Fatigue | Change at Cycle 1: Fatigue | Change at Cycle 2: Fatigue | Change at Cycle 3: Fatigue | Change at Cycle 4: Fatigue | Change at Cycle 5: Fatigue | Change at Cycle 9: Fatigue | Change at Cycle 14: Fatigue | Change at EoT: Fatigue | Change at FU Month 6: Fatigue | Change at FU Month 12: Fatigue | Baseline: Financial Difficulties | Change at Cycle 1: Financial Difficulties | Change at Cycle 2: Financial Difficulties | Change at Cycle 3: Financial Difficulties | Change at Cycle 4: Financial Difficulties | Change at Cycle 5: Financial Difficulties | Change at Cycle 9: Financial Difficulties | Change at Cycle 14: Financial Difficulties | Change at EoT: Financial Difficulties | Change at FU Month 6: Financial Difficulties | Change at FU Month 12: Financial Difficulties | Baseline: Insomnia | Change at Cycle 1: Insomnia | Change at Cycle 2: Insomnia | Change at Cycle 3: Insomnia | Change at Cycle 4: Insomnia | Change at Cycle 5: Insomnia | Change at Cycle 9: Insomnia | Change at Cycle 14: Insomnia | Change at EoT: Insomnia | Change at FU Month 6: Insomnia | Change at FU Month 12: Insomnia | Baseline: Nausea/Vomiting | Change at Cycle 1: Nausea/Vomiting | Change at Cycle 2: Nausea/Vomiting | Change at Cycle 3: Nausea/Vomiting | Change at Cycle 4: Nausea/Vomiting | Change at Cycle 5: Nausea/Vomiting | Change at Cycle 9: Nausea/Vomiting | Change at Cycle 14: Nausea/Vomiting | Change at EoT: Nausea/Vomiting | Change at FU Month 6: Nausea/Vomiting | Change at FU Month 12: Nausea/Vomiting | Baseline: Pain | Change at Cycle 1: Pain | Change at Cycle 2: Pain | Change at Cycle 3: Pain | Change at Cycle 4: Pain | Change at Cycle 5: Pain | Change at Cycle 9: Pain | Change at Cycle 14: Pain | Change at EoT: Pain | Change at FU Month 6: Pain | Change at FU Month 12: Pain | Baseline: Cognitive Functioning | Change at Cycle 1: Cognitive Functioning | Change at Cycle 2: Cognitive Functioning | Change at Cycle 3: Cognitive Functioning | Change at Cycle 4: Cognitive Functioning | Change at Cycle 5: Cognitive Functioning | Change at Cycle 9: Cognitive Functioning | Change at Cycle 14: Cognitive Functioning | Change at EoT: Cognitive Functioning | Change at FU Month 6: Cognitive Functioning | Change at FU Month 12: Cognitive Functioning | Baseline: Emotional Functioning | Change at Cycle 1: Emotional Functioning | Change at Cycle 2: Emotional Functioning | Change at Cycle 3: Emotional Functioning | Change at Cycle 4: Emotional Functioning | Change at Cycle 5: Emotional Functioning | Change at Cycle 9: Emotional Functioning | Change at Cycle 14: Emotional Functioning | Change at EoT: Emotional Functioning | Change at FU Month 6: Emotional Functioning | Change at FU Month 12: Emotional Functioning | Baseline: Physical Functioning | Change at Cycle 1: Physical Functioning | Change at Cycle 2: Physical Functioning | Change at Cycle 3: Physical Functioning | Change at Cycle 4: Physical Functioning | Change at Cycle 5: Physical Functioning | Change at Cycle 9: Physical Functioning | Change at Cycle 14: Physical Functioning | Change at EoT: Physical Functioning | Change at FU Month 6: Physical Functioning | Change at FU Month 12: Physical Functioning | Baseline: Role Functioning | Change at Cycle 1: Role Functioning | Change at Cycle 2: Role Functioning | Change at Cycle 3: Role Functioning | Change at Cycle 4: Role Functioning | Change at Cycle 5: Role Functioning | Change at Cycle 9: Role Functioning | Change at Cycle 14: Role Functioning | Change at EoT: Role Functioning | Change at FU Month 6: Role Functioning | Change at FU Month 12: Role Functioning | Baseline: Social Functioning | Change at Cycle 1: Social Functioning | Change at Cycle 2: Social Functioning | Change at Cycle 3: Social Functioning | Change at Cycle 4: Social Functioning | Change at Cycle 5: Social Functioning | Change at Cycle 9: Social Functioning | Change at Cycle 14: Social Functioning | Change at EoT: Social Functioning | Change at FU Month 6: Social Functioning | Change at FU Month 12: Social Functioning | Baseline: Global Health Status | Change at Cycle 1: Global Health Status | Change at Cycle 2: Global Health Status | Change at Cycle 3: Global Health Status | Change at Cycle 4: Global Health Status | Change at Cycle 5: Global Health Status | Change at Cycle 9: Global Health Status | Change at Cycle 14: Global Health Status | Change at EoT: Global Health Status | Change at FU Month 6: Global Health Status | Change at FU Month 12: Global Health Status |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 8.2 | 12.2 | 15.2 | 14.3 | 16.2 | 12.0 | 5.7 | 2.2 | 0.5 | -1.3 | -2.2 | 9.6 | 8.4 | 1.1 | 2.0 | 2.5 | 0.5 | -0.7 | 0.6 | 0.2 | 3.4 | 2.8 | 5.2 | 4.7 | 32.5 | 28.4 | 26.5 | 23.9 | 12.6 | 12.5 | 10.3 | -0.3 | -0.3 | 5.8 | 10.4 | 11.6 | 13.4 | 14.3 | 13.7 | 7.8 | 6.8 | 7.6 | 7.0 | 6.2 | 21.5 | 13.2 | 15.4 | 15.3 | 16.0 | 14.9 | 8.4 | 6.7 | 5.5 | 2.8 | 1.9 | 20.1 | 2.2 | 2.0 | 3.9 | 3.7 | 3.4 | 0.9 | -1.4 | -1.1 | -3.8 | -5.1 | 23.9 | 3.6 | 6.0 | 6.2 | 8.6 | 5.2 | 4.3 | 2.7 | 2.5 | 0.9 | 0.0 | 2.6 | 10.4 | 6.0 | 5.0 | 4.7 | 4.0 | 1.1 | 1.1 | 0.9 | 0.2 | 0.5 | 17.4 | 1.8 | 5.0 | 3.5 | 5.4 | 5.2 | 3.4 | 2.0 | 1.9 | 0.8 | 0.0 | 88.6 | -9.7 | -9.4 | -10.1 | -11.8 | -10.8 | -8.3 | -8.1 | -8.7 | -8.0 | -7.1 | 76.0 | -1.1 | -1.0 | -0.9 | -2.5 | -1.2 | 3.1 | 4.1 | 3.0 | 4.7 | 5.8 | 88.4 | -6.0 | -7.8 | -7.1 | -8.4 | -8.3 | -4.0 | -2.7 | -2.2 | -0.6 | -0.1 | 83.1 | -5.1 | -9.7 | -8.9 | -10.7 | -9.4 | -3.3 | -0.5 | -0.2 | 2.2 | 2.6 | 83.0 | -8.0 | -10.1 | -9.5 | -10.3 | -8.7 | -1.7 | -0.1 | 0.3 | 3.3 | 4.6 | 74.3 | -7.5 | -12.4 | -11.7 | -12.7 | -12.1 | -5.9 | -3.9 | -3.5 | -0.6 | -0.2 |
EORTC Quality of Life Questionnaire-Breast Cancer 23 (QLQ-BR23) Score
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30. There are 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. Higher scores for symptom scales represent higher levels of symptoms/problems. For functional scales, positive change from baseline indicated improvement in quality of life (QOL) while negative change from baseline indicated a deterioration. For symptom scales, positive change from baseline indicated deterioration and negative change indicated improvement. (NCT01966471)
Timeframe: Baseline, Cycles 1, 2, 3, 4, 5, 9, 14, End of Treatment, Follow-up Month 6, Follow-up Month 12, Follow-up Month 18
| Intervention | Units on a Scale (Mean) |
|---|
| Baseline: Arm Symptoms | Change at Cycle 1: Arm Symptoms | Change at Cycle 2: Arm Symptoms | Change at Cycle 3: Arm Symptoms | Change at Cycle 4: Arm Symptoms | Change at Cycle 5: Arm Symptoms | Change at Cycle 9: Arm Symptoms | Change at Cycle 14: Arm Symptoms | Change at EoT: Arm Symptoms | Change at FU Month 6: Arm Symptoms | Change at FU Month 12: Arm Symptoms | Baseline: Breast Symptoms | Change at Cycle 1: Breast Symptoms | Change at Cycle 2: Breast Symptoms | Change at Cycle 3: Breast Symptoms | Change at Cycle 4: Breast Symptoms | Change at Cycle 5: Breast Symptoms | Change at Cycle 9: Breast Symptoms | Change at Cycle 14: Breast Symptoms | Change at EoT: Breast Symptoms | Change at FU Month 6: Breast Symptoms | Change at FU Month 12: Breast Symptoms | Baseline: Systemic Therapy Side Effects (SE) | Change at Cycle 1: Systemic Therapy SE | Change at Cycle 2: Systemic Therapy SE | Change at Cycle 3: Systemic Therapy SE | Change at Cycle 4: Systemic Therapy SE | Change at Cycle 5: Systemic Therapy SE | Change at Cycle 9: Systemic Therapy SE | Change at Cycle 14: Systemic Therapy SE | Change at EoT: Systemic Therapy SE | Change at FU Month 6: Systemic Therapy SE | Change at FU Month 12: Systemic Therapy SE | Baseline: Upset by Hair Loss Item | Change at Cycle 1: Upset by Hair Loss Item | Change at Cycle 2: Upset by Hair Loss Item | Change at Cycle 3: Upset by Hair Loss Item | Change at Cycle 4: Upset by Hair Loss Item | Change at Cycle 5: Upset by Hair Loss Item | Change at Cycle 9: Upset by Hair Loss Item | Change at Cycle 14: Upset by Hair Loss Item | Change at EoT: Upset by Hair Loss Item | Change at FU Month 6: Upset by Hair Loss Item | Change at FU Month 12: Upset by Hair Loss Item | Baseline: Body Image | Change at Cycle 1: Body Image | Change at Cycle 2: Body Image | Change at Cycle 3: Body Image | Change at Cycle 4: Body Image | Change at Cycle 5: Body Image | Change at Cycle 9: Body Image | Change at Cycle 14: Body Image | Change at EoT: Body Image | Change at FU Month 6: Body Image | Change at FU Month 12: Body Image | Baseline: Future Perspectives (FP) | Change at Cycle 1: FP | Change at Cycle 2: FP | Change at Cycle 3: FP | Change at Cycle 4: FP | Change at Cycle 5: FP | Change at Cycle 9: FP | Change at Cycle 14: FP | Change at EoT: FP | Change at FU Month 6: FP | Change at FU Month 12: FP | Baseline: Sexual Enjoyment | Change at Cycle 1: Sexual Enjoyment | Change at Cycle 2: Sexual Enjoyment | Change at Cycle 3: Sexual Enjoyment | Change at Cycle 4: Sexual Enjoyment | Change at Cycle 5: Sexual Enjoyment | Change at Cycle 9: Sexual Enjoyment | Change at Cycle 14: Sexual Enjoyment | Change at EoT: Sexual Enjoyment | Change at FU Month 6: Sexual Enjoyment | Change at FU Month 12: Sexual Enjoyment | Baseline: Sexual Function | Change at Cycle 1: Sexual Function | Change at Cycle 2: Sexual Function | Change at Cycle 3: Sexual Function | Change at Cycle 4: Sexual Function | Change at Cycle 5: Sexual Function | Change at Cycle 9: Sexual Function | Change at Cycle 14: Sexual Function | Change at EoT: Sexual Function | Change at FU Month 6: Sexual Function | Change at FU Month 12: Sexual Function |
|---|
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 19.5 | -3.1 | -3.0 | -3.5 | -2.9 | -2.6 | -1.1 | 1.3 | 0.4 | -1.3 | -2.8 | 16.8 | -2.5 | -2.9 | -3.1 | -3.3 | -2.6 | 0.3 | 0.5 | 0.3 | -1.5 | -3.7 | 8.7 | 23.3 | 18.3 | 15.1 | 13.2 | 11.8 | 10.4 | 9.8 | 8.5 | 4.2 | 4.2 | 14.2 | 25.2 | 21.8 | 21.4 | 19.7 | 10.0 | 6.0 | 2.5 | 0.0 | -3.5 | -2.8 | 78.9 | -13.3 | -10.1 | -6.6 | -5.9 | -5.0 | -4.2 | -2.4 | -2.9 | 0.3 | 0.7 | 49.8 | -0.3 | 3.7 | 6.5 | 7.8 | 9.7 | 8.4 | 7.9 | 7.6 | 12.6 | 13.1 | 46.7 | -8.2 | -10.7 | -8.9 | -9.2 | -8.8 | -7.4 | -9.7 | -9.7 | -3.0 | -2.3 | 18.3 | -3.5 | -4.4 | -3.3 | -3.4 | -3.0 | -1.8 | -2.8 | -1.7 | 0.6 | 0.9 |
,| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 19.9 | -1.3 | -2.8 | -3.5 | -2.0 | -0.5 | -0.2 | 0.3 | 0.1 | -0.1 | -0.8 | 17.5 | -2.3 | -3.3 | -4.0 | -3.9 | -3.1 | 1.7 | -0.2 | -1.0 | -2.5 | -4.2 | 8.5 | 24.9 | 24.1 | 23.4 | 23.1 | 20.0 | 9.5 | 7.5 | 7.2 | 5.8 | 5.4 | 13.2 | 35.1 | 28.7 | 28.8 | 28.4 | 26.4 | 11.8 | 9.3 | 17.3 | 6.2 | 2.4 | 78.5 | -13.7 | -12.7 | -11.5 | -11.4 | -10.5 | -5.9 | -4.5 | -3.3 | -1.3 | 0.0 | 49.3 | -1.3 | 1.4 | 3.2 | 4.2 | 5.9 | 8.2 | 9.5 | 8.5 | 10.5 | 15.0 | 43.4 | -5.9 | -9.5 | -11.4 | -11.9 | -14.2 | -9.4 | -3.9 | -6.5 | -4.6 | -5.7 | 16.7 | -2.3 | -4.8 | -5.6 | -6.8 | -5.9 | -3.4 | -1.8 | -1.5 | 1.6 | 0.9 |
Percentage of Participants With Adverse Events
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 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. Preexisting conditions which worsen during a study are also considered as adverse events. AEs were reported based on the national cancer institute common terminology criteria for AEs, Version 4.0 (NCI-CTCAE, v4.0). (NCT01966471)
Timeframe: From randomization to approximately 7.5 years
| Intervention | Percentage of participants (Number) |
|---|
| Anthracycline Followed by Trastuzumab, Pertuzumab, and Taxane | 98.5 |
| Anthracycline Followed by Trastuzumab Emtansine and Pertuzumab | 99.1 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Arm I (Combination Chemotherapy, Surgery, Radiation) | 41.2 |
| Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation) | 45.8 |
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
| Intervention | percentage of pts with cardiac toxicity (Number) |
|---|
| Arm I (Combination Chemotherapy, Surgery, Radiation) | 4.46 |
| Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation) | 4.46 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Arm I (Combination Chemotherapy, Surgery, Radiation) | 44.4 |
| Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation) | 47.1 |
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)
| Intervention | percentage of participants with pCR (Number) |
|---|
| Premenopausal Women | Postmenopausal Women |
|---|
| Arm I (Combination Chemotherapy, Surgery, Radiation) | 44.2 | 38.2 |
,| Arm II (Chemo, Estrogen Deprivation, Surgery, Radiation) | 46.2 | 45.5 |
Percentage of Participants Undergoing Breast-Conserving Surgery
Percentage of participants undergoing a breast-conserving procedure versus a modified radical mastectomy at final surgery, performed 2 to 4 weeks after the last chemotherapy cycle (Week 18) (NCT02005549)
Timeframe: 20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab+Docetaxel+Capecitabine | 83 |
Percentage of Participants With pCR, Clinical Complete Response (CR), or Clinical Partial Response (PR)
Percentage of participants with pCR plus the percentage of participants without pCR who achieved CR or PR as measured by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. 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 have decreased to normal (short axis less than [<] 10 millimeters [mm]). No new lesions. PR was defined as greater than or equal to (≥) 30 percent (%) 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. (NCT02005549)
Timeframe: Baseline, 20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab+Docetaxel+Capecitabine | 72.22 |
Percentage of Participants With Pathological Complete Response (pCR)
pCR was defined as the absence of signs for invasive tumor in the final surgical sample as judged by the local pathologist. Surgery was performed 2 to 4 weeks after the last chemotherapy cycle. (NCT02005549)
Timeframe: Baseline, 20-24 weeks (final surgery, performed 2 to 4 weeks after the last chemotherapy cycle [Week 18])
| Intervention | percentage of participants (Number) |
|---|
| Bevacizumab+Docetaxel+Capecitabine | 22.22 |
PFS as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP
PFS is defined as the time between the date of randomization and the date of first documented PD or death, whichever occurs first. Participants who are alive and have not experienced PD at the time of analysis were censored at the time of the last tumor assessment. Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day. PD: 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, or presence of new lesions. (NCT02008227)
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 4.1 |
| Atezolizumab | 2.8 |
Progression-Free Survival (PFS) as Determined by Investigator Using RECIST v1.1: PP-ITT
PFS is defined as the time between the date of randomization and the date of first documented PD or death, whichever occurs first. Participants who are alive and have not experienced PD at the time of analysis were censored at the time of the last tumor assessment. Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day. PD: 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, or presence of new lesions. (NCT02008227)
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 4.0 |
| Atezolizumab | 2.8 |
EORTC QLQ-LC13 Questionnaire Score: Pain in Arm or Shoulder
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for pain in arm or shoulder. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Pain in Arm or Shoulder: Baseline (n= 384, 405) | Pain in Arm or Shoulder: C2D1(n= 332, 358) | Pain in Arm or Shoulder: C3D1(n= 248, 294) | Pain in Arm or Shoulder: C4D1(n= 217, 270) | Pain in Arm or Shoulder: C5D1(n= 164, 232) | Pain in Arm or Shoulder: C6D1(n= 147, 219) | Pain in Arm or Shoulder: C7D1(n= 86, 184) | Pain in Arm or Shoulder: C8D1(n=69, 163) | Pain in Arm or Shoulder: C9D1(n= 50, 149) | Pain in Arm or Shoulder: C10D1(n= 46, 141) | Pain in Arm or Shoulder: C11D1(n= 36, 127) | Pain in Arm or Shoulder: C12D1(n= 30, 126) | Pain in Arm or Shoulder: C13D1(n= 19, 117) | Pain in Arm or Shoulder: C14D1(n= 18, 117) | Pain in Arm or Shoulder: C15D1(n= 16, 108) | Pain in Arm or Shoulder: C16D1(n= 13, 104) | Pain in Arm or Shoulder: C17D1(n= 11, 93) | Pain in Arm or Shoulder: C18D1(n= 10, 88) | Pain in Arm or Shoulder: C19D1(n= 9, 80) | Pain in Arm or Shoulder: C20D1(n= 9, 76) | Pain in Arm or Shoulder: C21D1(n= 9, 71) | Pain in Arm or Shoulder: C22D1(n= 8, 65) | Pain in Arm or Shoulder: C23D1(n= 8, 62) | Pain in Arm or Shoulder: C24D1(n= 5, 59) | Pain in Arm or Shoulder: C25D1(n= 3, 57) | Pain in Arm or Shoulder: C26D1(n= 2, 52) | Pain in Arm or Shoulder: C27D1(n= 3, 49) | Pain in Arm or Shoulder: C28D1(n= 2, 45) | Pain in Arm or Shoulder: C29D1(n= 2, 37) | Pain in Arm or Shoulder: C30D1(n= 1, 30) | Pain in Arm or Shoulder: C31D1(n= 0, 23) | Pain in Arm or Shoulder: C32D1(n= 0, 22) | Pain in Arm or Shoulder: C33D1(n= 0, 15) | Pain in Arm or Shoulder: C34D1(n= 0, 14) | Pain in Arm or Shoulder: C35D1(n= 0, 11) | Pain in Arm or Shoulder: C36D1(n= 0, 8) | Pain in Arm or Shoulder: C37D1(n= 0, 5) | Pain in Arm or Shoulder: C38D1(n= 0, 2) | Pain in Arm or Shoulder: EOT(n= 264, 242) | Pain in Arm or Shoulder: Pro Week 6 Pd(n= 0,1) | Pain in Arm or Shoulder: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 20.16 | 18.34 | 16.44 | 18.15 | 14.94 | 15.68 | 16.67 | 16.77 | 16.78 | 17.73 | 15.49 | 16.93 | 14.81 | 15.67 | 15.74 | 14.10 | 16.49 | 18.18 | 20.83 | 18.42 | 12.68 | 13.33 | 15.05 | 18.08 | 14.62 | 15.38 | 14.97 | 11.85 | 10.81 | 10.00 | 10.14 | 13.64 | 20.00 | 16.67 | 27.27 | 16.67 | 33.33 | 0.00 | 23.14 | 66.67 | 33.33 |
,| Docetaxel | 20.49 | 19.58 | 17.20 | 14.75 | 16.06 | 15.42 | 14.73 | 15.94 | 14.00 | 14.49 | 11.11 | 12.22 | 12.28 | 11.11 | 12.50 | 7.69 | 9.09 | 13.33 | 7.41 | 11.11 | 11.11 | 16.67 | 16.67 | 20.00 | 11.11 | 16.67 | 11.11 | 0.00 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 21.72 | NA | 83.33 |
EORTC QLQ-LC13 Questionnaire Score: Hemoptysis
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for hemoptysis. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Hemoptysis: Baseline (n= 386, 406) | Hemoptysis: C2D1(n= 336, 359) | Hemoptysis: C3D1(n= 251, 301) | Hemoptysis: C4D1(n= 220, 270) | Hemoptysis: C5D1(n= 163, 234) | Hemoptysis: C6D1(n= 148, 219) | Hemoptysis: C7D1(n= 87, 187) | Hemoptysis: C8D1(n=70, 166) | Hemoptysis: C9D1(n= 50, 151) | Hemoptysis: C10D1(n= 47, 143) | Hemoptysis: C11D1(n= 37, 130) | Hemoptysis: C12D1(n= 30, 129) | Hemoptysis: C13D1(n= 19, 121) | Hemoptysis: C14D1(n= 18, 119) | Hemoptysis: C15D1(n= 16, 110) | Hemoptysis: C16D1(n= 13, 106) | Hemoptysis: C17D1(n= 11, 94) | Hemoptysis: C18D1(n= 10, 90) | Hemoptysis: C19D1(n= 9, 82) | Hemoptysis: C20D1(n= 9, 78) | Hemoptysis: C21D1(n= 8, 73) | Hemoptysis: C22D1(n= 8, 67) | Hemoptysis: C23D1(n= 8, 64) | Hemoptysis: C24D1(n= 5, 61) | Hemoptysis: C25D1(n= 3, 58) | Hemoptysis: C26D1(n= 3, 53) | Hemoptysis: C27D1(n= 3, 50) | Hemoptysis: C28D1(n= 2, 46) | Hemoptysis: C29D1(n= 2, 38) | Hemoptysis: C30D1(n= 1, 31) | Hemoptysis: C31D1(n= 0, 24) | Hemoptysis: C32D1(n= 0, 23) | Hemoptysis: C33D1(n= 0,16) | Hemoptysis: C34D1(n= 0, 14) | Hemoptysis: C35D1(n= 0, 11) | Hemoptysis: C36D1(n= 0, 8) | Hemoptysis: C37D1(n= 0, 5) | Hemoptysis: C38D1(n= 0, 2) | Hemoptysis: EOT(n= 264, 243) | Hemoptysis: Pro Week 6 Pd(n= 0,1) | Hemoptysis: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 3.86 | 3.16 | 3.10 | 2.10 | 1.42 | 1.22 | 1.43 | 2.41 | 1.77 | 0.70 | 1.03 | 1.03 | 1.10 | 1.68 | 1.82 | 2.83 | 2.84 | 2.96 | 2.03 | 2.56 | 1.83 | 1.99 | 1.04 | 2.73 | 3.45 | 3.77 | 2.00 | 1.45 | 0.88 | 1.08 | 2.78 | 2.90 | 0.00 | 0.00 | 0.00 | 4.17 | 0.00 | 0.00 | 6.04 | 0.00 | 0.00 |
,| Docetaxel | 4.32 | 4.76 | 4.38 | 2.88 | 1.43 | 1.80 | 1.15 | 1.90 | 2.00 | 2.84 | 1.80 | 0.00 | 3.51 | 1.85 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 33.33 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 5.18 | NA | 33.33 |
EORTC QLQ Core 30 (C30) Questionnaire Score: Single Items
EORTC QLQ-C30 included global health status (GHS)/quality of life (QOL), functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement). (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Appetite Loss: Baseline (n= 390, 413) | Appetite Loss: Cycle (C) 2 Day (D) 1(n= 342, 368) | Appetite Loss: C3D1(n= 256, 304) | Appetite Loss: C4D1(n= 224, 279) | Appetite Loss: C5D1(n= 166, 238) | Appetite Loss: C6D1(n= 151, 224) | Appetite Loss: C7D1(n= 88, 190) | Appetite Loss: C8D1(n= 72, 170) | Appetite Loss: C9D1(n= 50, 153) | Appetite Loss: C10D1(n= 47, 146) | Appetite Loss: C11D1(n= 37, 134) | Appetite Loss: C12D1(n= 30, 132) | Appetite Loss: C13D1(n= 19, 123) | Appetite Loss: C14D1(n= 18, 120) | Appetite Loss: C15D1(n= 16, 113) | Appetite Loss: C16D1(n= 13, 109) | Appetite Loss: C17D1(n= 11, 98) | Appetite Loss: C18D1(n= 10, 91) | Appetite Loss: C19D1(n= 9, 84) | Appetite Loss: C20D1(n= 9, 80) | Appetite Loss: C21D1(n= 9, 75) | Appetite Loss: C22D1(n= 8, 69) | Appetite Loss: C23D1(n= 8, 66) | Appetite Loss: C24D1(n= 5, 64) | Appetite Loss: C25D1(n= 3, 60) | Appetite Loss: C26D1(n= 3, 55) | Appetite Loss: C27D1(n= 3, 52) | Appetite Loss: C28D1(n= 1, 49) | Appetite Loss: C29D1(n= 2, 40) | Appetite Loss: C30D1(n= 1, 31) | Appetite Loss: C31D1(n= 0, 24) | Appetite Loss: C32D1(n= 0, 22) | Appetite Loss: C33D1(n= 0,16) | Appetite Loss: C34D1(n= 0, 14) | Appetite Loss: C35D1(n= 0, 12) | Appetite Loss: C36D1(n= 0, 8) | Appetite Loss: C37D1(n= 0, 5) | Appetite Loss: C38D1(n= 0, 2) | Appetite Loss: End of treatment (EOT)(n= 265, 246) | Appetite Loss: Pro Week 6 Pd(n= 0,1) | Appetite Loss: Survival Follow-up (FU) 1 (n= 2, 1) | Constipation: Baseline (n= 388, 410) | Constipation: C2D1(n= 339, 363) | Constipation: C3D1(n= 255, 304) | Constipation: C4D1(n= 224, 277) | Constipation: C5D1(n= 166, 236) | Constipation: C6D1(n= 151, 225) | Constipation: C7D1(n= 87, 188) | Constipation: C8D1(n= 72, 171) | Constipation: C9D1(n= 50, 153) | Constipation: C10D1(n= 47, 146) | Constipation: C11D1(n= 37, 134) | Constipation: C12D1(n= 30, 132) | Constipation: C13D1(n= 19, 124) | Constipation: C14D1(n= 17, 121) | Constipation: C15D1(n= 15, 113) | Constipation: C16D1(n= 13, 109) | Constipation: C17D1(n= 11, 98) | Constipation: C18D1(n= 10, 92) | Constipation: C19D1(n= 9, 83) | Constipation: C20D1(n=9, 80) | Constipation: C21D1(n= 9, 75) | Constipation: C22D1(n= 8, 69) | Constipation: C23D1(n= 8, 66) | Constipation: C24D1(n=5, 65) | Constipation: C25D1(n= 3, 60) | Constipation: C26D1(n= 2, 55) | Constipation: C27D1(n= 3, 52) | Constipation: C28D1(n= 1, 48) | Constipation: C29D1(n= 2, 40) | Constipation: C30D1(n= 1, 31) | Constipation: C31D1(n= 0, 24) | Constipation: C32D1(n= 0, 22) | Constipation: C33D1(n= 0, 16) | Constipation: C34D1(n= 0, 14) | Constipation: C35D1(n= 0, 12) | Constipation: C36D1(n= 0, 8) | Constipation: C37D1(n= 0, 5) | Constipation: C38D1(n= 0, 2) | Constipation: EOT (n= 265, 246) | Constipation: Pro Week 6 Pd(n= 0,1) | Constipation: Survival FU-1 (n= 2,1) | Diarrhea: Baseline (n= 388, 411) | Diarrhea: C2D1(n= 339, 361) | Diarrhea: C3D1(n= 255, 304) | Diarrhea: C4D1(n= 223, 280) | Diarrhea: C5D1(n= 166, 238) | Diarrhea: C6D1(n= 151, 222) | Diarrhea: C7D1(n= 87, 189) | Diarrhea: C8D1(n= 72, 171) | Diarrhea: C9D1(n= 50, 153) | Diarrhea: C10D1(n= 47, 146) | Diarrhea: C11D1(n= 36, 134) | Diarrhea: C12D1(n= 30, 132) | Diarrhea: C13D1(n= 18, 124) | Diarrhea: C14D1(n= 17, 121) | Diarrhea: C15D1(n= 15, 113) | Diarrhea: C16D1(n= 12, 108) | Diarrhea: C17D1(n= 11, 98) | Diarrhea: C18D1(n= 10, 92) | Diarrhea: C19D1(n= 9, 84) | Diarrhea: C20D1(n= 9, 80) | Diarrhea: C21D1(n= 9, 75) | Diarrhea: C22D1(n= 8, 68) | Diarrhea: C23D1(n= 8, 66) | Diarrhea: C24D1(n= 5, 64) | Diarrhea: C25D1(n= 3, 60) | Diarrhea: C26D1(n= 3, 55) | Diarrhea: C27D1(n= 3, 52) | Diarrhea: C28D1(n= 1, 48) | Diarrhea: C29D1(n= 2, 40) | Diarrhea: C30D1(n= 1, 31) | Diarrhea: C31D1(n= 0, 24) | Diarrhea: C32D1(n= 0, 22) | Diarrhea: C33D1(n= 0, 16) | Diarrhea: C34D1(n= 0, 14) | Diarrhea: C35D1(n= 0, 12) | Diarrhea: C36D1(n= 0, 8) | Diarrhea: C37D1(n= 0, 5) | Diarrhea: C38D1(n= 0, 2) | Diarrhea: EOT(n= 265, 246) | Diarrhea: Pro Week 6 Pd(n= 0, 1) | Diarrhea: Survival FU-1 (n= 2, 1) | Financial Difficulties: Baseline (n=387, 411) | Financial Difficulties: C2D1 (n=336, 362) | Financial Difficulties: C3D1 (n=253, 305) | Financial Difficulties: C4D1 (n=219, 280) | Financial Difficulties: C5D1 (n=165, 238) | Financial Difficulties: C6D1 (n=149, 224) | Financial Difficulties: C7D1 (n=86, 189) | Financial Difficulties: C8D1 (n=71, 170) | Financial Difficulties: C9D1 (n=49, 152) | Financial Difficulties: C10D1 (n=46, 146) | Financial Difficulties: C11D1 (n=36, 134) | Financial Difficulties: C12D1 (n=30, 132) | Financial Difficulties: C13D1 (n=18, 122) | Financial Difficulties: C14D1 (n=17, 121) | Financial Difficulties: C15D1 (n=15, 113) | Financial Difficulties: C16D1 (n=12, 109) | Financial Difficulties: C17D1 (n=11, 98) | Financial Difficulties: C18D1 (n=10, 92) | Financial Difficulties: C19D1 (n=9, 84) | Financial Difficulties: C20D1 (n=9, 80) | Financial Difficulties: C21D1 (n=9, 75) | Financial Difficulties: C22D1 (n=8, 68) | Financial Difficulties: C23D1 (n=7, 66) | Financial Difficulties: C24D1 (n=5, 64) | Financial Difficulties: C25D1 (n=3, 60) | Financial Difficulties: C26D1 (n=3, 55) | Financial Difficulties: C27D1 (n=3, 52) | Financial Difficulties: C28D1 (n=1, 48) | Financial Difficulties: C29D1 (n=2, 40) | Financial Difficulties: C30D1 (n=1, 31) | Financial Difficulties: C31D1(n=0, 24) | Financial Difficulties: C32D1(n=0, 22) | Financial Difficulties: C33D1(n=0, 16) | Financial Difficulties: C34D1(n=0, 14) | Financial Difficulties: C35D1(n=0, 12) | Financial Difficulties: C36D1(n=0, 8) | Financial Difficulties: C37D1(n=0, 5) | Financial Difficulties: C38D1(n=0, 2) | Financial Difficulties: EOT(n=263, 245) | Financial Difficulties: Pro Week 6 Pd (n=0, 1) | Financial Difficulties:Survival FU-1 (n=2,24) | Insomnia: Baseline (n= 388, 413) | Insomnia: C2D1(n= 340, 367) | Insomnia: C3D1(n= 253, 304) | Insomnia: C4D1(n= 222, 279) | Insomnia: C5D1(n= 166, 237) | Insomnia: C6D1(n= 150, 225) | Insomnia: C7D1(n= 87, 189) | Insomnia: C8D1(n= 70, 169) | Insomnia: C9D1(n= 49, 153) | Insomnia: C10D1(n= 46, 144) | Insomnia: C11D1(n= 36, 133) | Insomnia: C12D1(n= 29, 132) | Insomnia: C13D1(n= 17, 124) | Insomnia: C14D1(n= 17, 121) | Insomnia: C15D1(n= 15, 113) | Insomnia: C16D1(n= 13, 108) | Insomnia: C17D1(n= 11, 98) | Insomnia: C18D1(n= 10, 92) | Insomnia: C19D1(n= 9, 83) | Insomnia: C20D1(n= 9, 80) | Insomnia: C21D1(n= 9, 75) | Insomnia: C22D1(n= 8, 69) | Insomnia: C23D1(n= 8, 66) | Insomnia: C24D1(n= 5, 64) | Insomnia: C25D1(n= 3, 60) | Insomnia: C26D1(n= 3, 55) | Insomnia: C27D1(n= 3, 52) | Insomnia: C28D1(n= 1, 49) | Insomnia: C29D1(n= 2, 40) | Insomnia: C30D1(n= 1, 31) | Insomnia: C31D1(n= 0, 24) | Insomnia: C32D1(n= 0, 22) | Insomnia: C33D1(n= 0, 16) | Insomnia: C34D1(n= 0, 14) | Insomnia: C35D1(n= 0, 12) | Insomnia: C36D1(n= 0, 8) | Insomnia: C37D1(n= 0, 5) | Insomnia: C38D1(n= 0, 2) | Insomnia: EOT(n= 264, 246) | Insomnia: Pro Week Pd(n= 0, 1) | Insomnia: Survival FU-1 (n= 2, 1) | Dyspnea: C1D1 (n= 389, 412) | Dyspnea: C2D1 (n= 341, 368) | Dyspnea: C3D1 (n= 255, 302) | Dyspnea: C4D1 (n= 389, 277) | Dyspnea: C5D1 (n= 222, 236) | Dyspnea: C6D1 (n= 166, 222) | Dyspnea: C7D1 (n= 151, 188) | Dyspnea: C8D1 (n= 86, 169) | Dyspnea: C9D1 (n= 72, 152) | Dyspnea: C10D1 (n= 50, 146) | Dyspnea: C11D1 (n= 47, 134) | Dyspnea: C12D1 (n= 37, 132) | Dyspnea: C13D1 (n= 30, 123) | Dyspnea: C14D1 (n= 19, 119) | Dyspnea: C15D1 (n= 16, 113) | Dyspnea: C16D1 (n= 13, 109) | Dyspnea: C17D1 (n= 11, 98) | Dyspnea: C18D1 (n= 10, 92) | Dyspnea: C19D1 (n= 9, 84) | Dyspnea: C20D1 (n= 9, 80) | Dyspnea: C21D1 (n= 9, 75) | Dyspnea: C22D1 (n= 8, 68) | Dyspnea: C23D1 (n= 8, 65) | Dyspnea: C24D1 (n= 5, 64) | Dyspnea: C25D1 (n= 3, 60) | Dyspnea: C26D1 (n= 3, 55) | Dyspnea: C27D1 (n= 3, 52) | Dyspnea: C28D1 (n= 1, 49) | Dyspnea: C29D1 (n= 2, 40) | Dyspnea: C30D1 (n= 1, 31) | Dyspnea: C31D1 (n= 0, 24) | Dyspnea: C32D1 (n= 0, 22) | Dyspnea: C33D1 (n= 0, 16) | Dyspnea: C34D1 (n= 0, 14) | Dyspnea: C35D1 (n= 0, 12) | Dyspnea: C36D1 (n= 0, 8) | Dyspnea: C37D1 (n= 0, 5) | Dyspnea: C38D1 (n= 0, 2) | Dyspnea: EOT(n= 266, 247) | Dyspnea: Pro Week 6 Pd (n= 0, 1) | Dyspnea: Survival Follow-Up 1 (n= 2, 1) |
|---|
| Atezolizumab | 22.92 | 26.99 | 21.16 | 18.40 | 16.67 | 14.88 | 12.46 | 12.94 | 11.33 | 12.33 | 11.44 | 8.84 | 8.40 | 10.00 | 12.39 | 10.09 | 7.82 | 8.06 | 9.13 | 9.58 | 12.44 | 6.76 | 7.58 | 8.33 | 6.11 | 5.45 | 9.62 | 7.48 | 9.17 | 1.08 | 6.94 | 7.58 | 8.33 | 4.76 | 8.33 | 4.17 | 6.67 | 0.00 | 31.98 | 33.33 | 66.67 | 16.50 | 18.09 | 15.13 | 14.56 | 12.15 | 12.89 | 11.52 | 12.28 | 10.68 | 9.82 | 9.95 | 10.86 | 8.60 | 9.09 | 10.03 | 9.79 | 9.86 | 9.06 | 9.64 | 12.50 | 14.22 | 11.59 | 10.10 | 9.74 | 11.11 | 12.12 | 13.46 | 11.81 | 15.83 | 8.60 | 9.72 | 6.06 | 4.17 | 7.14 | 5.56 | 4.17 | 0.00 | 0.00 | 19.78 | 66.67 | 66.67 | 7.22 | 7.29 | 6.14 | 6.67 | 6.58 | 6.31 | 7.94 | 8.77 | 7.63 | 5.48 | 4.98 | 6.31 | 5.65 | 9.92 | 7.96 | 6.48 | 7.82 | 8.70 | 7.94 | 6.67 | 11.11 | 7.84 | 6.06 | 6.25 | 6.11 | 10.30 | 5.77 | 4.86 | 9.17 | 7.53 | 6.94 | 12.12 | 8.33 | 4.76 | 5.56 | 4.17 | 6.67 | 0.00 | 9.35 | 0.00 | 33.33 | 18.09 | 15.93 | 15.63 | 15.12 | 15.13 | 16.67 | 17.46 | 18.82 | 17.54 | 17.81 | 19.65 | 18.43 | 18.31 | 18.46 | 18.29 | 18.65 | 18.37 | 19.57 | 19.05 | 18.75 | 23.11 | 18.63 | 21.72 | 20.83 | 21.67 | 20.00 | 17.31 | 18.06 | 19.17 | 17.20 | 20.83 | 21.21 | 22.92 | 26.19 | 27.78 | 8.33 | 26.67 | 16.67 | 19.46 | 33.33 | 66.67 | 26.15 | 26.52 | 24.89 | 23.66 | 25.88 | 23.41 | 23.99 | 23.87 | 22.88 | 21.53 | 20.55 | 21.46 | 23.39 | 23.69 | 21.53 | 21.60 | 20.07 | 21.38 | 22.49 | 20.83 | 20.89 | 18.84 | 19.70 | 19.79 | 18.89 | 21.21 | 19.23 | 21.09 | 21.67 | 20.43 | 20.83 | 19.70 | 20.83 | 23.81 | 25.00 | 25.00 | 33.33 | 16.67 | 29.95 | 66.67 | 100.00 | 32.04 | 31.88 | 27.15 | 28.28 | 27.82 | 26.88 | 25.53 | 26.43 | 24.12 | 23.52 | 22.89 | 22.73 | 25.47 | 21.85 | 22.71 | 21.71 | 21.43 | 22.83 | 23.41 | 21.67 | 19.11 | 20.59 | 18.46 | 19.79 | 20.00 | 20.00 | 16.03 | 17.01 | 15.00 | 16.13 | 22.22 | 22.73 | 25.00 | 26.19 | 25.00 | 20.83 | 26.67 | 33.33 | 39.41 | 33.33 | 33.33 |
,| Docetaxel | 26.58 | 27.49 | 21.35 | 18.75 | 18.88 | 18.98 | 15.91 | 13.89 | 8.00 | 7.80 | 11.71 | 11.11 | 10.53 | 7.41 | 6.25 | 7.69 | 6.06 | 6.67 | 7.41 | 11.11 | 3.70 | 8.33 | 8.33 | 13.33 | 0.00 | 22.22 | 0.00 | 0.00 | 33.33 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 29.81 | NA | 50.00 | 19.93 | 19.47 | 19.74 | 17.86 | 13.05 | 14.35 | 13.41 | 8.33 | 9.33 | 9.22 | 5.41 | 11.11 | 5.26 | 15.69 | 2.22 | 20.51 | 12.12 | 6.67 | 7.41 | 14.81 | 7.41 | 12.50 | 4.17 | 20.00 | 0.00 | 0.00 | 0.00 | 0.00 | 50.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 19.12 | NA | 33.33 | 5.84 | 11.21 | 10.07 | 8.22 | 8.43 | 7.51 | 10.34 | 7.41 | 11.33 | 7.80 | 8.33 | 10.00 | 11.11 | 3.92 | 8.89 | 13.89 | 9.09 | 13.33 | 14.81 | 7.41 | 18.52 | 16.67 | 8.33 | 6.67 | 0.00 | 11.11 | 11.11 | 0.00 | 50.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 10.57 | NA | 33.33 | 20.76 | 18.45 | 16.86 | 16.74 | 16.57 | 15.66 | 16.28 | 13.15 | 16.33 | 14.49 | 9.26 | 12.22 | 12.96 | 15.69 | 6.67 | 13.89 | 15.15 | 10.00 | 3.70 | 11.11 | 11.11 | 12.50 | 9.52 | 13.33 | 0.00 | 0.00 | 0.00 | 0.00 | 50.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 21.80 | NA | 83.33 | 28.87 | 27.55 | 25.69 | 21.32 | 21.49 | 22.00 | 21.07 | 15.24 | 16.33 | 13.77 | 9.26 | 16.09 | 17.65 | 25.49 | 22.22 | 20.51 | 21.21 | 20.00 | 18.52 | 18.52 | 22.22 | 16.67 | 20.83 | 26.67 | 11.11 | 11.11 | 11.11 | 0.00 | 33.33 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 28.91 | NA | 50.00 | 33.50 | 32.55 | 29.93 | 28.38 | 29.52 | 30.02 | 27.13 | 28.70 | 26.67 | 27.66 | 25.23 | 26.67 | 19.30 | 20.37 | 16.67 | 20.51 | 15.15 | 20.00 | 11.11 | 18.52 | 18.52 | 20.83 | 12.50 | 6.67 | 11.11 | 0.00 | 0.00 | 0.00 | 33.33 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 38.72 | NA | 33.33 |
EORTC QLQ-C30 Questionnaire Score: Functional Subscales
EORTC QLQ-C30 included GHS/QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement). (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Cognitive: Baseline (n= 390, 411) | Cognitive: C2D1 (n= 341, 363) | Cognitive: C3D1(n= 256, 305) | Cognitive: C4D1(n= 224, 281) | Cognitive: C5D1(n= 166, 238) | Cognitive: C6D1(n= 151, 224) | Cognitive: C7D1(n= 87, 189) | Cognitive: C8D1(n= 72, 171) | Cognitive: C9D1(n= 50, 153) | Cognitive: C10D1(n= 47, 146) | Cognitive: C11D1(n= 36, 134) | Cognitive: C12D1(n= 30, 132) | Cognitive: C13D1(n= 18, 124) | Cognitive: C14D1(n= 17, 121) | Cognitive: C15D1(n= 15, 113) | Cognitive: C16D1(n= 12, 109) | Cognitive: C17D1(n= 11, 98) | Cognitive: C18D1(n= 10, 92) | Cognitive: C19D1(n= 9, 84) | Cognitive: C20D1(n= 9, 80) | Cognitive: C21D1(n= 9, 75) | Cognitive: C22D1(n= 8, 68) | Cognitive: C23D1(n= 8, 66) | Cognitive: C24D1(n= 5, 64) | Cognitive: C25D1(n= 3, 60) | Cognitive: C26D1(n= 3, 55) | Cognitive: C27D1(n= 3, 52) | Cognitive: C28D1(n= 1, 48) | Cognitive: C29D1(n= 2, 40) | Cognitive: C30D1(n= 1, 31) | Cognitive: C31D1(n= 0, 24) | Cognitive: C32D1(n= 0, 22) | Cognitive: C33D1(n= 0,16) | Cognitive: C34D1(n= 0, 14) | Cognitive: C35D1(n= 0, 12) | Cognitive: C36D1(n= 0, 8) | Cognitive: C37D1(n= 0, 5) | Cognitive: C38D1(n= 0, 2) | Cognitive: EOT (n= 266, 246) | Cognitive: Pro Week 6 Pd(n= 0,1) | Cognitive: Survival FU 1 (n= 2, 1) | Emotional: Baseline (n= 390, 411) | Emotional: C2D1(n= 341, 363) | Emotional: C3D1(n= 256, 305) | Emotional: C4D1(n= 224, 280) | Emotional: C5D1(n= 166, 238) | Emotional: C6D1(n= 151, 224) | Emotional: C7D1(n= 87, 189) | Emotional: C8D1(n= 72, 171) | Emotional: C9D1(n= 50, 153) | Emotional: C10D1(n= 47, 146) | Emotional: C11D1(n= 36, 134) | Emotional: C12D1(n= 30, 132) | Emotional: C13D1(n= 18, 123) | Emotional: C14D1(n= 17, 121) | Emotional: C15D1(n= 15, 113) | Emotional: C16D1(n= 12, 109) | Emotional: C17D1(n= 11, 98) | Emotional: C18D1(n= 10, 92) | Emotional: C19D1(n= 9, 84) | Emotional: C20D1(n=9, 80) | Emotional: C21D1(n= 9, 75) | Emotional: C22D1(n= 8, 68) | Emotional: C23D1(n= 8, 66) | Emotional: C24D1(n=5, 65) | Emotional: C25D1(n= 3, 60) | Emotional: C26D1(n= 3, 55) | Emotional: C27D1(n= 3, 52) | Emotional: C28D1(n= 1, 48) | Emotional: C29D1(n= 2, 40) | Emotional: C30D1(n= 1, 31) | Emotional: C31D1(n= 0, 24) | Emotional: C32D1(n= 0, 22) | Emotional: C33D1(n= 0, 16) | Emotional: C34D1(n= 0, 14) | Emotional: C35D1(n= 0, 12) | Emotional: C36D1(n= 0, 8) | Emotional: C37D1(n= 0, 5) | Emotional: C38D1(n= 0, 2) | Emotional: EOT (n= 265, 246) | Emotional: Pro Week 6 Pd(n= 0,1) | Emotional: Survival FU-1 (n= 2,1) | Physical: Baseline (n= 390, 413) | Physical: C2D1(n= 343, 369) | Physical: C3D1(n= 255, 304) | Physical: C4D1(n= 224, 277) | Physical: C5D1(n= 167, 238) | Physical: C6D1(n= 151, 225) | Physical: C7D1(n= 88, 189) | Physical: C8D1(n= 71, 170) | Physical: C9D1(n= 50, 153) | Physical: C10D1(n= 47, 146) | Physical: C11D1(n= 37, 134) | Physical: C12D1(n= 30, 132) | Physical: C13D1(n= 19, 124) | Physical: C14D1(n= 18, 121) | Physical: C15D1(n= 16, 113) | Physical: C16D1(n= 13, 109) | Physical: C17D1(n= 11, 98) | Physical: C18D1(n= 10, 92) | Physical: C19D1(n= 9, 84) | Physical: C20D1(n= 9, 80) | Physical: C21D1(n= 9, 75) | Physical: C22D1(n= 8, 69) | Physical: C23D1(n= 8, 66) | Physical: C24D1(n= 5, 64) | Physical: C25D1(n= 3, 60) | Physical: C26D1(n= 3, 55) | Physical: C27D1(n= 2, 52) | Physical: C28D1(n= 2, 49) | Physical: C29D1(n= 2, 40) | Physical: C30D1(n= 1, 31) | Physical: C31D1(n= 0, 24) | Physical: C32D1(n= 0, 22) | Physical: C33D1(n= 0, 16) | Physical: C34D1(n= 0, 14) | Physical: C35D1(n= 0, 12) | Physical: C36D1(n= 0, 8) | Physical: C37D1(n= 0, 5) | Physical: C38D1(n= 0, 2) | Physical: EOT(n= 267, 246) | Physical: Pro Week 6 Pd(n= 0, 1) | Physical: Survival FU-1 (n= 2, 1) | Role: Baseline (n=388, 413) | Role: C2D1 (n=339, 369) | Role: C3D1 (n=256, 304) | Role: C4D1 (n=224, 279) | Role: C5D1 (n=167, 238) | Role: C6D1 (n=151, 225) | Role: C7D1 (n=88, 190) | Role: C8D1 (n=72, 170) | Role: C9D1 (n=50, 153) | Role: C10D1 (n=47, 145) | Role: C11D1 (n=37, 134) | Role: C12D1 (n=30, 132) | Role: C13D1 (n=19, 124) | Role: C14D1 (n=18, 121) | Role: C15D1 (n=16, 113) | Role: C16D1 (n=13, 109) | Role: C17D1 (n=11, 98) | Role: C18D1 (n=10, 92) | Role: C19D1 (n=9, 84) | Role: C20D1 (n=9, 80) | Role: C21D1 (n=9, 75) | Role: C22D1 (n=8, 69) | Role: C23D1 (n=8, 66) | Role: C24D1 (n=5, 65) | Role: C25D1 (n=3, 60) | Role: C26D1 (n=3, 55) | Role: C27D1 (n=3, 52) | Role: C28D1 (n=1, 49) | Role: C29D1 (n=2, 40) | Role: C30D1 (n=1, 31) | Role: C31D1(n=0, 24) | Role: C32D1(n=0, 22) | Role: C33D1(n=0, 16) | Role: C34D1(n=0, 14) | Role: C35D1(n=0, 12) | Role: C36D1(n=0, 8) | Role: C37D1(n=0, 5) | Role: C38D1(n=0, 2) | Role: EOT(n=266, 246) | Role: Pro Week 6 Pd (n=0, 1) | Role: Survival FU-1 (n=2,1) | Social: Baseline (n= 389, 411) | Social: C2D1(n= 340, 363) | Social: C3D1(n= 255, 305) | Social: C4D1(n= 223, 280) | Social: C5D1(n= 166, 238) | Social: C6D1(n= 151, 224) | Social: C7D1(n= 87, 189) | Social: C8D1(n= 72, 171) | Social: C9D1(n= 50, 153) | Social: C10D1(n= 47, 146) | Social: C11D1(n= 36, 134) | Social: C12D1(n= 30, 132) | Social: C13D1(n= 18, 124) | Social: C14D1(n= 17, 121) | Social: C15D1(n= 15, 113) | Social: C16D1(n= 12, 109) | Social: C17D1(n= 11, 98) | Social: C18D1(n= 10, 92) | Social: C19D1(n= 9, 84) | Social: C20D1(n= 9, 80) | Social: C21D1(n= 9, 75) | Social: C22D1(n= 8, 68) | Social: C23D1(n= 8, 66) | Social: C24D1(n= 5, 65) | Social: C25D1(n= 3, 60) | Social: C26D1(n= 3, 55) | Social: C27D1(n= 3, 52) | Social: C28D1(n= 1, 48) | Social: C29D1(n= 2, 40) | Social: C30D1(n= 1, 31) | Social: C31D1(n= 0, 24) | Social: C32D1(n= 0, 22) | Social: C33D1(n= 0, 16) | Social: C34D1(n= 0, 14) | Social: C35D1(n= 0, 12) | Social: C36D1(n= 0, 8) | Social: C37D1(n= 0, 5) | Social: C38D1(n= 0, 2) | Social: EOT(n= 264, 245) | Social: Pro Week 6 Pd(n= 0, 1) | Social: Survival FU-1 (n= 2, 1) |
|---|
| Atezolizumab | 85.16 | 84.94 | 86.28 | 85.35 | 84.38 | 84.45 | 84.74 | 85.58 | 85.95 | 86.53 | 85.95 | 84.22 | 84.27 | 85.67 | 85.10 | 85.32 | 85.37 | 82.97 | 83.53 | 82.29 | 83.78 | 84.56 | 84.09 | 83.85 | 83.61 | 82.73 | 85.26 | 85.07 | 83.75 | 86.02 | 80.56 | 82.58 | 77.08 | 80.95 | 76.39 | 83.33 | 83.33 | 91.67 | 78.52 | 83.33 | 0.00 | 76.55 | 79.47 | 82.71 | 83.69 | 81.99 | 82.70 | 83.77 | 83.63 | 85.62 | 84.13 | 84.16 | 84.34 | 84.35 | 84.25 | 83.87 | 82.11 | 83.25 | 82.52 | 81.42 | 83.19 | 84.19 | 86.03 | 87.00 | 83.72 | 83.66 | 85.15 | 86.38 | 86.92 | 87.50 | 89.79 | 85.76 | 82.95 | 81.25 | 82.14 | 83.33 | 95.83 | 90.00 | 83.33 | 73.92 | 66.67 | 33.33 | 74.46 | 71.70 | 76.19 | 76.79 | 77.79 | 78.93 | 79.20 | 78.87 | 79.46 | 79.41 | 79.09 | 79.72 | 80.48 | 80.33 | 79.88 | 78.82 | 78.57 | 79.64 | 78.97 | 79.19 | 78.67 | 82.51 | 80.81 | 81.41 | 83.22 | 80.12 | 81.89 | 84.15 | 83.00 | 83.01 | 78.61 | 75.15 | 77.92 | 75.24 | 73.89 | 83.33 | 74.67 | 86.67 | 64.78 | 46.67 | 46.67 | 73.61 | 68.29 | 75.27 | 76.70 | 76.05 | 77.70 | 79.04 | 77.35 | 79.30 | 81.38 | 78.61 | 79.80 | 79.44 | 79.48 | 79.20 | 76.45 | 76.02 | 77.17 | 78.17 | 78.54 | 77.33 | 81.64 | 80.30 | 78.72 | 79.44 | 76.97 | 80.77 | 82.99 | 83.33 | 81.72 | 79.86 | 75.00 | 66.67 | 69.05 | 69.44 | 87.50 | 76.67 | 100.00 | 60.03 | 66.67 | 33.33 | 77.41 | 76.86 | 81.15 | 81.31 | 82.00 | 81.99 | 82.80 | 81.19 | 83.77 | 83.79 | 81.47 | 82.95 | 84.27 | 84.16 | 83.92 | 82.72 | 82.99 | 81.34 | 81.94 | 81.46 | 78.67 | 84.31 | 80.56 | 80.77 | 81.39 | 79.70 | 82.05 | 84.03 | 82.92 | 79.57 | 79.17 | 73.48 | 73.96 | 67.86 | 70.83 | 87.50 | 80.00 | 100.00 | 70.00 | 66.67 | 16.67 |
,| Docetaxel | 83.38 | 83.38 | 84.05 | 84.82 | 86.04 | 86.09 | 87.55 | 89.58 | 90.00 | 91.13 | 92.59 | 91.11 | 90.74 | 92.16 | 93.33 | 97.22 | 96.97 | 91.67 | 92.59 | 90.74 | 87.04 | 89.58 | 95.83 | 83.33 | 72.22 | 77.78 | 88.89 | 100.00 | 50.00 | 100.00 | NA | NA | NA | NA | NA | NA | NA | NA | 78.82 | NA | 50.00 | 75.83 | 78.06 | 79.70 | 81.67 | 80.52 | 81.73 | 81.42 | 84.38 | 86.00 | 84.93 | 89.12 | 86.94 | 89.35 | 86.27 | 90.00 | 88.89 | 88.64 | 87.50 | 87.96 | 76.85 | 83.33 | 76.74 | 89.58 | 78.33 | 100.00 | 86.11 | 100.00 | 100.00 | 50.00 | 100.00 | NA | NA | NA | NA | NA | NA | NA | NA | 73.78 | NA | 25.00 | 73.27 | 72.64 | 74.98 | 75.72 | 77.30 | 74.77 | 77.61 | 78.45 | 79.07 | 79.29 | 81.44 | 82.22 | 87.37 | 85.56 | 86.25 | 85.13 | 84.24 | 82.67 | 87.41 | 81.48 | 87.41 | 82.50 | 85.00 | 80.00 | 82.22 | 75.56 | 76.67 | 65.00 | 56.67 | 80.00 | NA | NA | NA | NA | NA | NA | NA | NA | 63.59 | NA | 36.67 | 70.92 | 69.91 | 74.61 | 73.36 | 74.35 | 73.62 | 77.27 | 73.61 | 77.67 | 78.72 | 80.63 | 81.11 | 84.21 | 78.70 | 83.33 | 85.90 | 80.30 | 80.00 | 85.19 | 79.63 | 85.19 | 79.17 | 85.42 | 70.00 | 77.78 | 83.33 | 88.89 | 100.00 | 66.67 | 100.00 | NA | NA | NA | NA | NA | NA | NA | NA | 58.52 | NA | 33.33 | 74.16 | 74.51 | 78.37 | 79.60 | 79.32 | 78.15 | 80.65 | 81.94 | 82.00 | 81.21 | 82.41 | 86.67 | 89.81 | 86.27 | 93.33 | 84.72 | 87.88 | 86.67 | 88.89 | 81.48 | 85.19 | 85.42 | 91.67 | 80.00 | 77.78 | 77.78 | 88.89 | 100.00 | 50.00 | 100.00 | NA | NA | NA | NA | NA | NA | NA | NA | 69.51 | NA | 83.33 |
EORTC QLQ-C30 Questionnaire Score: GHS Scale
EORTC QLQ-C30 included GHS/QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement). (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Global Health: Baseline (n= 387, 410) | Global Health: C2D1(n= 339, 361) | Global Health: C3D1(n= 255, 304) | Global Health: C4D1(n= 222, 279) | Global Health: C5D1(n= 166, 235) | Global Health: C6D1(n= 151, 223) | Global Health: C7D1(n= 87, 187) | Global Health: C8D1(n= 72, 169) | Global Health: C9D1(n= 50, 152) | Global Health: C10D1(n= 47, 145) | Global Health: C11D1(n= 36, 133) | Global Health: C12D1(n= 30, 131) | Global Health: C13D1(n= 18, 124) | Global Health: C14D1(n= 17, 120) | Global Health: C15D1(n= 15, 113) | Global Health: C16D1(n= 12, 109) | Global Health: C17D1(n= 10, 98) | Global Health: C18D1(n= 10, 92) | Global Health: C19D1(n= 9, 84) | Global Health: C20D1(n= 9, 80) | Global Health: C21D1(n= 9, 75) | Global Health: C22D1(n= 8, 68) | Global Health: C23D1(n= 8, 66) | Global Health: C24D1(n= 5, 65) | Global Health: C25D1(n= 3, 60) | Global Health: C26D1(n= 3, 55) | Global Health: C27D1(n= 3, 52) | Global Health: C28D1(n= 2, 48) | Global Health: C29D1(n= 2, 40) | Global Health: C30D1(n= 1, 30) | Global Health: C31D1(n= 0, 24) | Global Health: C32D1(n= 0, 22) | Global Health: C33D1(n= 0,16) | Global Health: C34D1(n= 0, 14) | Global Health: C35D1(n= 0, 12) | Global Health: C36D1(n= 0, 8) | Global Health: C37D1(n= 0, 5) | Global Health: C38D1(n= 0, 2) | Global Health: EOT(n= 262, 245) | Global Health: Pro Week 6 Pd(n= 0,1) | Global Health: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 61.24 | 58.93 | 64.61 | 65.11 | 66.35 | 65.73 | 66.93 | 67.36 | 68.09 | 69.37 | 68.17 | 68.32 | 67.74 | 67.01 | 68.66 | 67.97 | 68.62 | 68.57 | 68.25 | 68.12 | 66.56 | 73.28 | 70.45 | 69.36 | 69.03 | 68.64 | 68.91 | 71.87 | 72.71 | 75.28 | 71.53 | 70.45 | 67.19 | 68.45 | 69.44 | 80.21 | 76.67 | 91.67 | 52.82 | 50.00 | 33.33 |
,| Docetaxel | 60.55 | 59.56 | 64.64 | 63.51 | 64.01 | 64.51 | 64.85 | 62.73 | 67.17 | 66.84 | 69.68 | 66.67 | 69.91 | 69.61 | 69.44 | 62.50 | 61.67 | 61.67 | 65.74 | 62.04 | 60.19 | 54.17 | 62.50 | 70.00 | 66.67 | 66.67 | 66.67 | 87.50 | 91.67 | 83.33 | NA | NA | NA | NA | NA | NA | NA | NA | 51.69 | NA | 58.33 |
EORTC QLQ-C30 Questionnaire Score: Symptom Subscale
EORTC QLQ-C30 included GHS/QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). For this instrument, GHS/QOL and functional scales were linearly transformed so each score ranged 0-100, where lower scores indicate poorer functioning (e.g., worsening) and higher scores indicate better functioning (e.g., improvement). Symptom scales/items were also linearly transformed so each score ranged 0-100, where higher scores indicate worse symptoms (e.g., more severe/worsened) and lower scores indicate less symptoms (e.g., less severe/improvement). (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Nausea/Vomiting: Baseline (n= 389, 413) | Nausea/Vomiting: C2D1(n= 342, 369) | Nausea/Vomiting: C3D1(n= 253, 305) | Nausea/Vomiting: C4D1(n= 223, 279) | Nausea/Vomiting: C5D1(n= 167, 238) | Nausea/Vomiting: C6D1(n= 151, 225) | Nausea/Vomiting: C7D1(n= 88, 190) | Nausea/Vomiting: C8D1(n= 72, 170) | Nausea/Vomiting: C9D1(n= 50, 153) | Nausea/Vomiting: C10D1(n= 47, 146) | Nausea/Vomiting: C11D1(n= 37, 134) | Nausea/Vomiting: C12D1(n= 30, 132) | Nausea/Vomiting: C13D1(n= 19, 124) | Nausea/Vomiting: C14D1(n= 18, 121) | Nausea/Vomiting: C15D1(n= 16, 113) | Nausea/Vomiting: C16D1(n= 13, 109) | Nausea/Vomiting: C17D1(n= 11, 98) | Nausea/Vomiting: C18D1(n= 10, 92) | Nausea/Vomiting: C19D1(n= 9, 84) | Nausea/Vomiting: C20D1(n= 9, 80) | Nausea/Vomiting: C21D1(n= 9, 75) | Nausea/Vomiting: C22D1(n= 8, 69) | Nausea/Vomiting: C23D1(n= 8, 66) | Nausea/Vomiting: C24D1(n= 5, 64) | Nausea/Vomiting: C25D1(n= 3, 60) | Nausea/Vomiting: C26D1(n= 3, 55) | Nausea/Vomiting: C27D1(n= 3, 52) | Nausea/Vomiting: C28D1(n= 1, 49) | Nausea/Vomiting: C29D1(n= 2, 40) | Nausea/Vomiting: C30D1(n= 1, 31) | Nausea/Vomiting: C31D1(n= 0, 24) | Nausea/Vomiting: C32D1(n= 0, 22) | Nausea/Vomiting: C33D1(n= 0,16) | Nausea/Vomiting: C34D1(n= 0, 14) | Nausea/Vomiting: C35D1(n= 0, 12) | Nausea/Vomiting: C36D1(n= 0, 8) | Nausea/Vomiting: C37D1(n= 0, 5) | Nausea/Vomiting: C38D1(n= 0, 2) | Nausea/Vomiting: EOT(n= 266, 245) | Nausea/Vomiting: Pro Week 6 Pd(n= 0,1) | Nausea/Vomiting: Survival FU 1 (n= 2, 1) | Pain: Baseline (n= 390, 413) | Pain: C2D1(n= 343, 368) | Pain: C3D1(n= 256, 305) | Pain: C4D1(n= 224, 280) | Pain: C5D1(n= 167, 239) | Pain: C6D1(n= 151, 225) | Pain: C7D1(n= 88, 190) | Pain: C8D1(n= 72, 171) | Pain: C9D1(n= 50, 153) | Pain: C10D1(n= 47, 146) | Pain: C11D1(n= 37, 134) | Pain: C12D1(n= 30, 132) | Pain: C13D1(n= 19, 124) | Pain: C14D1(n= 18, 120) | Pain: C15D1(n= 16, 113) | Pain: C16D1(n= 13, 109) | Pain: C17D1(n= 11, 98) | Pain: C18D1(n= 10, 92) | Pain: C19D1(n= 9, 84) | Pain: C20D1(n=9, 80) | Pain: C21D1(n= 9, 75) | Pain: C22D1(n= 8, 69) | Pain: C23D1(n= 8, 66) | Pain: C24D1(n=5, 64) | Pain: C25D1(n= 3, 60) | Pain: C26D1(n= 3, 55) | Pain: C27D1(n= 3, 52) | Pain: C28D1(n= 1, 49) | Pain: C29D1(n= 2, 40) | Pain: C30D1(n= 1, 31) | Pain: C31D1(n= 0, 24) | Pain: C32D1(n= 0, 22) | Pain: C33D1(n= 0, 16) | Pain: C34D1(n= 0, 14) | Pain: C35D1(n= 0, 12) | Pain: C36D1(n= 0, 8) | Pain: C37D1(n= 0, 5) | Pain: C38D1(n= 0, 2) | Pain: EOT (n= 267, 247) | Pain: Pro Week 6 Pd(n= 0,1) | Pain: Survival FU-1 (n= 2,1) | Fatigue: Baseline (n= 390, 413) | Fatigue: C2D1(n= 343, 369) | Fatigue: C3D1(n= 256, 304) | Fatigue: C4D1(n= 224, 278) | Fatigue: C5D1(n= 167, 238) | Fatigue: C6D1(n= 151, 225) | Fatigue: C7D1(n= 88, 190) | Fatigue: C8D1(n= 72, 170) | Fatigue: C9D1(n= 50, 153) | Fatigue: C10D1(n= 47, 145) | Fatigue: C11D1(n= 37, 134) | Fatigue: C12D1(n= 30, 132) | Fatigue: C13D1(n= 19, 124) | Fatigue: C14D1(n= 18, 121) | Fatigue: C15D1(n= 16, 112) | Fatigue: C16D1(n= 13, 109) | Fatigue: C17D1(n= 11, 98) | Fatigue: C18D1(n= 10, 92) | Fatigue: C19D1(n= 9, 84) | Fatigue: C20D1(n= 9, 80) | Fatigue: C21D1(n= 9, 75) | Fatigue: C22D1(n= 8, 69) | Fatigue: C23D1(n= 8, 66) | Fatigue: C24D1(n= 5, 64) | Fatigue: C25D1(n= 3, 60) | Fatigue: C26D1(n= 3, 55) | Fatigue: C27D1(n= 3, 52) | Fatigue: C28D1(n= 1, 49) | Fatigue: C29D1(n= 2, 40) | Fatigue: C30D1(n= 1, 31) | Fatigue: C31D1(n= 0, 24) | Fatigue: C32D1(n= 0, 22) | Fatigue: C33D1(n= 0, 16) | Fatigue: C34D1(n= 0, 14) | Fatigue: C35D1(n= 0, 12) | Fatigue: C36D1(n= 0, 8) | Fatigue: C37D1(n= 0, 5) | Fatigue: C38D1(n= 0, 2) | Fatigue: EOT(n= 267, 246) | Fatigue: Pro Week 6 Pd(n= 0, 1) | Fatigue: Survival FU-1 (n= 2, 1) |
|---|
| Atezolizumab | 7.59 | 9.53 | 7.27 | 7.17 | 6.44 | 6.44 | 5.61 | 4.61 | 2.83 | 3.54 | 3.23 | 3.03 | 3.36 | 3.31 | 3.83 | 2.75 | 2.55 | 3.08 | 4.17 | 3.13 | 4.89 | 1.93 | 2.53 | 2.34 | 1.94 | 2.73 | 2.24 | 1.02 | 1.67 | 1.61 | 2.08 | 1.52 | 1.04 | 2.38 | 1.39 | 4.17 | 6.67 | 0.00 | 10.61 | 16.67 | 66.67 | 29.98 | 29.30 | 24.15 | 23.75 | 23.22 | 21.63 | 21.58 | 22.03 | 19.28 | 21.00 | 21.27 | 18.69 | 17.74 | 17.64 | 17.40 | 20.64 | 20.41 | 20.83 | 22.42 | 20.00 | 19.78 | 15.22 | 16.92 | 20.05 | 18.33 | 16.36 | 15.06 | 14.29 | 13.75 | 15.05 | 14.58 | 16.67 | 20.83 | 26.19 | 22.22 | 22.92 | 30.00 | 0.00 | 35.43 | 16.67 | 83.33 | 36.21 | 39.78 | 33.90 | 30.72 | 30.95 | 28.89 | 28.33 | 27.97 | 25.78 | 26.32 | 25.62 | 26.60 | 27.51 | 26.31 | 27.73 | 27.22 | 27.21 | 27.29 | 27.65 | 25.21 | 26.44 | 22.38 | 24.16 | 23.78 | 23.89 | 28.69 | 22.65 | 22.34 | 21.11 | 23.66 | 23.15 | 25.25 | 29.86 | 31.75 | 25.00 | 16.67 | 24.44 | 16.67 | 43.07 | 44.44 | 88.89 |
,| Docetaxel | 8.01 | 11.50 | 7.05 | 7.40 | 6.29 | 6.40 | 6.82 | 6.02 | 3.33 | 2.48 | 3.15 | 3.89 | 4.39 | 4.63 | 1.04 | 5.13 | 9.09 | 6.67 | 3.70 | 5.56 | 1.85 | 6.25 | 6.25 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 33.33 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 11.65 | NA | 50.00 | 29.70 | 28.43 | 22.59 | 21.65 | 20.96 | 22.41 | 21.59 | 23.38 | 16.33 | 14.54 | 13.96 | 13.33 | 16.67 | 12.04 | 10.42 | 21.79 | 16.67 | 11.67 | 14.81 | 27.78 | 14.81 | 18.75 | 14.58 | 30.00 | 16.67 | 22.22 | 11.11 | 0.00 | 41.67 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 32.21 | NA | 66.67 | 37.59 | 40.52 | 35.29 | 35.59 | 36.03 | 36.28 | 34.34 | 30.86 | 28.67 | 29.31 | 27.63 | 28.89 | 22.22 | 21.60 | 20.14 | 21.79 | 22.22 | 26.67 | 22.22 | 32.10 | 28.39 | 33.33 | 25.00 | 31.11 | 11.11 | 18.52 | 11.11 | 0.00 | 44.44 | 22.22 | NA | NA | NA | NA | NA | NA | NA | NA | 47.50 | NA | 83.33 |
DOR as Determined by Investigator Using RECIST v1.1: SP ITT
DOR:Duration from the first tumor assessment that supports the participant's objective response to PD or death due to any cause,whichever occurs first.CR:complete disappearance of all target lesions and non-target disease.All nodes,both target and non-target,must decrease to normal. No new lesions.PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR.Participants who have not experienced PD at the time of analysis were censored at the time of the last tumor assessment.Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day.PD: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.DOR was estimated using KM methodology. (NCT02008227)
Timeframe: From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 6.3 |
| Atezolizumab | 23.9 |
DOR as Determined by Investigator Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP
DOR:Duration from the first tumor assessment that supports the participant's objective response to PD or death due to any cause,whichever occurs first.CR:complete disappearance of all target lesions and non-target disease.All nodes,both target and non-target,must decrease to normal. No new lesions.PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR.Participants who have not experienced PD at the time of analysis were censored at the time of the last tumor assessment.Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day.PD: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.DOR was estimated using KM methodology. (NCT02008227)
Timeframe: From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 6.2 |
| Atezolizumab | 16.0 |
Duration of Response (DOR) as Determined by Investigator Using RECIST v1.1: PP-ITT
DOR:Duration from the first tumor assessment that supports the participant's objective response to PD or death due to any cause,whichever occurs first.CR:complete disappearance of all target lesions and non-target disease.All nodes,both target and non-target,must decrease to normal. No new lesions.PR: At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR.Participants who have not experienced PD at the time of analysis were censored at the time of the last tumor assessment.Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day.PD: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.DOR was estimated using KM methodology. (NCT02008227)
Timeframe: From first objective response of CR or PR to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 6.2 |
| Atezolizumab | 16.3 |
Maximum Observed Serum Atezolizumab Concentration (Cmax)
(NCT02008227)
Timeframe: Predose (Hr 0), 30 minutes (min) post-infusion (infusion duration: 60 min) on Cycle 1 Day 1 (1 Cycle=21 days)
| Intervention | Microgram per milliliter (mcg/mL) (Mean) |
|---|
| Atezolizumab | 400 |
OS: SP-ITT
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology. (NCT02008227)
Timeframe: Baseline until death due to any cause (up to approximately 2.87 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 9.8 |
| Atezolizumab | 13.3 |
OS: TC1/2/3 or IC1/2/3 Subgroup of PP
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology. (NCT02008227)
Timeframe: Baseline until death due to any cause (up to approximately 2.25 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 10.3 |
| Atezolizumab | 15.7 |
OS: TC1/2/3 Or IC1/2/3 Subgroup of SP
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology. (NCT02008227)
Timeframe: Baseline until death from any cause (approximately 2.87 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 10.8 |
| Atezolizumab | 14.3 |
OS: TC2/3 or IC2/3 Subgroup of SP
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology. (NCT02008227)
Timeframe: Baseline until death due to any cause (up to approximately 2.87 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 11.4 |
| Atezolizumab | 16.6 |
EORTC QLQ-LC13 Questionnaire Score: Pain in Chest
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for pain in chest. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Pain in Chest: Baseline (n= 385, 403) | Pain in Chest: C2D1(n= 332, 356) | Pain in Chest: C3D1(n= 249, 296) | Pain in Chest: C4D1(n= 217, 268) | Pain in Chest: C5D1(n= 164, 233) | Pain in Chest: C6D1(n= 145, 217) | Pain in Chest: C7D1(n= 86, 184) | Pain in Chest: C8D1(n=69, 164) | Pain in Chest: C9D1(n= 49, 149) | Pain in Chest: C10D1(n= 46, 142) | Pain in Chest: C11D1(n= 36, 127) | Pain in Chest: C12D1(n= 30, 128) | Pain in Chest: C13D1(n= 19, 120) | Pain in Chest: C14D1(n= 18, 118) | Pain in Chest: C15D1(n= 16, 109) | Pain in Chest: C16D1(n= 13, 105) | Pain in Chest: C17D1(n= 11, 94) | Pain in Chest: C18D1(n= 10, 89) | Pain in Chest: C19D1(n= 9, 80) | Pain in Chest: C20D1(n= 9, 76) | Pain in Chest: C21D1(n= 9, 71) | Pain in Chest: C22D1(n= 8, 66) | Pain in Chest: C23D1(n= 8, 62) | Pain in Chest: C24D1(n= 5, 61) | Pain in Chest: C25D1(n= 3, 57) | Pain in Chest: C26D1(n= 2, 52) | Pain in Chest: C27D1(n= 3, 49) | Pain in Chest: C28D1(n= 2, 45) | Pain in Chest: C29D1(n= 2, 37) | Pain in Chest: C30D1(n= 1, 31) | Pain in Chest: C31D1(n= 0, 24) | Pain in Chest: C32D1(n= 0, 23) | Pain in Chest: C33D1(n= 0, 16) | Pain in Chest: C34D1(n= 0, 14) | Pain in Chest: C35D1(n= 0, 11) | Pain in Chest: C36D1(n= 0, 8) | Pain in Chest: C37D1(n= 0, 5) | Pain in Chest: C38D1(n= 0, 2) | Pain in Chest: EOT(n= 265, 245) | Pain in Chest: Pro Week 6 Pd(n= 0,1) | Pain in Chest: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 19.52 | 15.26 | 15.43 | 14.43 | 12.16 | 12.60 | 11.78 | 14.02 | 10.74 | 8.45 | 9.45 | 8.85 | 7.50 | 7.63 | 8.56 | 8.25 | 8.87 | 7.49 | 7.50 | 10.09 | 7.98 | 7.58 | 7.53 | 8.20 | 8.77 | 10.90 | 8.84 | 8.15 | 8.11 | 5.38 | 4.17 | 13.04 | 14.58 | 14.29 | 6.06 | 4.17 | 6.67 | 0.00 | 19.46 | 0.00 | 33.33 |
,| Docetaxel | 17.92 | 16.67 | 14.59 | 14.44 | 11.99 | 12.18 | 12.40 | 10.63 | 7.48 | 5.07 | 3.70 | 3.33 | 3.51 | 5.56 | 6.25 | 5.13 | 0.00 | 6.67 | 7.41 | 3.70 | 0.00 | 4.17 | 4.17 | 0.00 | 0.00 | 0.00 | 11.11 | 0.00 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 18.99 | NA | 50.00 |
Overall Survival (OS): PP-ITT
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology. (NCT02008227)
Timeframe: Baseline until death due to any cause (up to approximately 2.25 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 9.6 |
| Atezolizumab | 13.8 |
Percentage of Participants Who Died: Tumor Cells (TC)1/2/3 or Tumor-Infiltrating Immune Cells (IC)1/2/3 Subgroup of PP
Percentage of participants who died among TC1/2/3 or IC1/2/3 subgroup of PP-ITT were reported. TC1 = presence of discernible programmed death-ligand 1 (PD-L1) staining of any intensity in >/=1% and <5% TCs; TC2: presence of discernible PD-L1 staining of any intensity in >/=5% and <50% TCs; TC3 = presence of discernible PD-L1 staining of any intensity in >/=50% TCs; IC1 = presence of discernible PD-L1 staining of any intensity in ICs covering between >/=1% and <5% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC2 = presence of discernible PD-L1 staining of any intensity in ICs covering between >/=5% and <10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma; IC3 = presence of discernible PD-L1 staining of any intensity in ICs covering >/=10% of tumor area occupied by tumor cells, associated intratumoral, and contiguous peri-tumoral desmoplastic stroma. (NCT02008227)
Timeframe: Baseline until death due to any cause (up to approximately 2.25 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel | 67.1 |
| Atezolizumab | 62.7 |
EORTC QLQ-LC13 Questionnaire Score: Dyspnea
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for dyspnea. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Dyspnea: Baseline (n= 386, 407) | Dyspnea: C2D1(n= 335, 361) | Dyspnea: C3D1(n= 252, 301) | Dyspnea: C4D1(n= 220, 273) | Dyspnea: C5D1(n= 165, 236) | Dyspnea: C6D1(n= 148, 221) | Dyspnea: C7D1(n= 87, 187) | Dyspnea: C8D1(n=70, 167) | Dyspnea: C9D1(n= 50, 151) | Dyspnea: C10D1(n= 47, 143) | Dyspnea: C11D1(n= 37, 130) | Dyspnea: C12D1(n= 30, 129) | Dyspnea: C13D1(n= 19, 121) | Dyspnea: C14D1(n= 18, 119) | Dyspnea: C15D1(n= 16, 110) | Dyspnea: C16D1(n= 13, 106) | Dyspnea: C17D1(n= 10, 95) | Dyspnea: C18D1(n= 10, 90) | Dyspnea: C19D1(n= 9, 82) | Dyspnea: C20D1(n= 9, 78) | Dyspnea: C21D1(n= 9, 73) | Dyspnea: C22D1(n= 8, 67) | Dyspnea: C23D1(n= 8, 64) | Dyspnea: C24D1(n= 5, 62) | Dyspnea: C25D1(n= 3, 58) | Dyspnea: C26D1(n= 3, 53) | Dyspnea: C27D1(n= 3, 50) | Dyspnea: C28D1(n= 2, 46) | Dyspnea: C29D1(n= 2, 38) | Dyspnea: C30D1(n= 1, 31) | Dyspnea: C31D1(n= 0, 24) | Dyspnea: C32D1(n= 0, 23) | Dyspnea: C33D1(n= 0,16) | Dyspnea: C34D1(n= 0, 14) | Dyspnea: C35D1(n= 0, 11) | Dyspnea: C36D1(n= 0, 8) | Dyspnea: C37D1(n= 0, 5) | Dyspnea: C38D1(n= 0, 2) | Dyspnea: EOT(n= 263, 246) | Dyspnea: Pro Week 6 Pd(n= 0,1) | Dyspnea: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 26.78 | 28.79 | 25.40 | 25.17 | 24.72 | 24.01 | 24.42 | 24.42 | 22.44 | 22.18 | 20.43 | 22.27 | 22.22 | 22.41 | 22.12 | 21.91 | 23.51 | 22.65 | 22.09 | 22.65 | 20.40 | 19.90 | 21.2 | 21.33 | 19.73 | 21.80 | 20.33 | 18.36 | 19.30 | 17.92 | 24.07 | 24.15 | 25.69 | 27.78 | 26.26 | 18.06 | 24.44 | 16.67 | 34.51 | 22.22 | 44.44 |
,| Docetaxel | 28.55 | 28.14 | 28.13 | 27.75 | 26.57 | 29.69 | 25.35 | 28.02 | 26.00 | 27.42 | 22.67 | 22.41 | 16.37 | 17.90 | 15.28 | 14.53 | 18.89 | 20.00 | 18.52 | 20.37 | 19.75 | 18.06 | 16.67 | 20.00 | 29.63 | 22.22 | 18.52 | 5.56 | 5.56 | 11.11 | NA | NA | NA | NA | NA | NA | NA | NA | 36.12 | NA | 66.67 |
EORTC QLQ-LC13 Questionnaire Score: Dysphagia
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for dysphagia. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Dysphagia: Baseline (n= 387, 406) | Dysphagia: C2D1(n= 336, 358) | Dysphagia: C3D1(n= 251, 301) | Dysphagia: C4D1(n= 217, 272) | Dysphagia: C5D1(n= 163, 236) | Dysphagia: C6D1(n= 147, 219) | Dysphagia: C7D1(n= 87, 187) | Dysphagia: C8D1(n=70, 167) | Dysphagia: C9D1(n= 50, 151) | Dysphagia: C10D1(n= 47, 143) | Dysphagia: C11D1(n= 37, 130) | Dysphagia: C12D1(n= 29, 129) | Dysphagia: C13D1(n= 19, 121) | Dysphagia: C14D1(n= 18, 119) | Dysphagia: C15D1(n= 16, 110) | Dysphagia: C16D1(n= 13, 106) | Dysphagia: C17D1(n= 11, 95) | Dysphagia: C18D1(n= 10, 90) | Dysphagia: C19D1(n= 9, 82) | Dysphagia: C20D1(n= 9, 78) | Dysphagia: C21D1(n= 9, 73) | Dysphagia: C22D1(n= 8, 67) | Dysphagia: C23D1(n= 8, 64) | Dysphagia: C24D1(n= 5, 62) | Dysphagia: C25D1(n= 3, 58) | Dysphagia: C26D1(n= 3, 53) | Dysphagia: C27D1(n= 3, 50) | Dysphagia: C28D1(n= 2, 46) | Dysphagia: C29D1(n= 2, 38) | Dysphagia: C30D1(n= 1, 31) | Dysphagia: C31D1(n= 0, 24) | Dysphagia: C32D1(n= 0, 23) | Dysphagia: C33D1(n= 0,16) | Dysphagia: C34D1(n= 0, 14) | Dysphagia: C35D1(n= 0, 11) | Dysphagia: C36D1(n= 0, 8) | Dysphagia: C37D1(n= 0, 5) | Dysphagia: C38D1(n= 0, 2) | Dysphagia: EOT(n= 264, 245) | Dysphagia: Pro Week 6 Pd(n= 0,1) | Dysphagia: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 5.09 | 6.42 | 5.43 | 5.88 | 6.64 | 4.72 | 5.70 | 4.79 | 4.64 | 5.36 | 2.82 | 3.88 | 3.86 | 5.04 | 3.33 | 3.77 | 3.86 | 4.44 | 5.28 | 4.70 | 5.02 | 2.99 | 3.65 | 4.84 | 4.02 | 4.40 | 2.67 | 4.35 | 4.39 | 5.38 | 5.56 | 7.25 | 6.25 | 9.52 | 3.03 | 4.17 | 6.67 | 0.00 | 8.98 | 0.00 | 0.00 |
,| Docetaxel | 6.20 | 10.22 | 9.16 | 8.60 | 6.75 | 6.80 | 4.21 | 5.71 | 1.33 | 1.42 | 1.80 | 2.30 | 0.00 | 5.56 | 0.00 | 0.00 | 3.03 | 0.00 | 3.70 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 10.23 | NA | 0.00 |
EORTC QLQ-LC13 Questionnaire Score: Coughing
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for coughing. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Coughing: Baseline (n= 383, 406) | Coughing: C2D1(n= 333, 360) | Coughing: C3D1(n= 250, 298) | Coughing: C4D1(n= 219, 272) | Coughing: C5D1(n= 164, 235) | Coughing: C6D1(n= 147, 219) | Coughing: C7D1(n= 87, 185) | Coughing: C8D1(n= 69, 166) | Coughing: C9D1(n= 50, 150) | Coughing: C10D1(n= 47, 140) | Coughing: C11D1(n= 37, 129) | Coughing: C12D1(n= 30, 129) | Coughing: C13D1(n= 19, 121) | Coughing: C14D1(n= 18, 119) | Coughing: C15D1(n= 16, 110) | Coughing: C16D1(n= 13, 106) | Coughing: C17D1(n= 11, 94) | Coughing: C18D1(n= 10, 90) | Coughing: C19D1(n= 9, 82) | Coughing: C20D1(n= 9, 78) | Coughing: C21D1(n= 9, 73) | Coughing: C22D1(n= 8, 67) | Coughing: C23D1(n= 8, 64) | Coughing: C24D1(n= 5, 62) | Coughing: C25D1(n= 3, 58) | Coughing: C26D1(n= 3, 53) | Coughing: C27D1(n= 3, 50) | Coughing: C28D1(n= 2, 46) | Coughing: C29D1(n= 2, 38) | Coughing: C30D1(n= 1, 31) | Coughing: C31D1(n= 0, 24) | Coughing: C32D1(n= 0, 23) | Coughing: C33D1(n= 0,16) | Coughing: C34D1(n= 0, 14) | Coughing: C35D1(n= 0, 11) | Coughing: C36D1(n= 0, 8) | Coughing: C37D1(n= 0, 5) | Coughing: C38D1(n= 0, 2) | Coughing: EOT(n= 262, 246) | Coughing: Pro Week 6 Pd(n= 0,1) | Coughing: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 37.27 | 37.50 | 33.89 | 32.48 | 31.35 | 31.05 | 30.99 | 29.12 | 29.11 | 27.86 | 27.39 | 25.06 | 24.79 | 24.37 | 25.76 | 24.53 | 24.82 | 26.30 | 25.61 | 28.21 | 28.77 | 22.89 | 23.44 | 24.73 | 25.86 | 26.41 | 24.67 | 20.29 | 19.30 | 18.28 | 23.61 | 26.09 | 27.08 | 26.19 | 21.21 | 25.00 | 26.67 | 33.33 | 38.48 | 33.33 | 33.33 |
,| Docetaxel | 38.73 | 36.54 | 33.73 | 31.35 | 32.72 | 31.75 | 32.95 | 30.43 | 24.67 | 23.40 | 21.62 | 20.00 | 15.79 | 16.67 | 12.50 | 20.51 | 21.21 | 26.67 | 22.22 | 25.93 | 22.22 | 25.00 | 20.83 | 26.67 | 33.33 | 44.44 | 11.11 | 16.67 | 16.67 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 35.75 | NA | 50.00 |
Percentage of Participants Who Died: PP-ITT
(NCT02008227)
Timeframe: Baseline until death due to any cause (up to approximately 2.25 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel | 70.1 |
| Atezolizumab | 63.8 |
EORTC QLQ-LC13 Questionnaire Score: Pain in Other Parts
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for pain in other parts. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Pain in Other Parts: Baseline (n= 373, 402) | Pain in Other Parts: C2D1(n= 320, 347) | Pain in Other Parts: C3D1(n= 239, 286) | Pain in Other Parts: C4D1(n= 211, 263) | Pain in Other Parts: C5D1(n= 154, 230) | Pain in Other Parts: C6D1(n= 139, 214) | Pain in Other Parts: C7D1(n= 81, 180) | Pain in Other Parts: C8D1(n=65, 158) | Pain in Other Parts: C9D1(n= 44, 135) | Pain in Other Parts: C10D1(n= 44, 136) | Pain in Other Parts: C11D1(n= 34, 123) | Pain in Other Parts: C12D1(n= 26, 122) | Pain in Other Parts: C13D1(n= 17, 113) | Pain in Other Parts: C14D1(n= 18, 115) | Pain in Other Parts: C15D1(n= 15, 106) | Pain in Other Parts: C16D1(n= 13, 105) | Pain in Other Parts: C17D1(n= 11, 93) | Pain in Other Parts: C18D1(n= 10, 89) | Pain in Other Parts: C19D1(n= 9, 80) | Pain in Other Parts: C20D1(n= 9, 74) | Pain in Other Parts: C21D1(n= 8, 69) | Pain in Other Parts: C22D1(n= 8, 62) | Pain in Other Parts: C23D1(n= 8, 62) | Pain in Other Parts: C24D1(n= 5, 61) | Pain in Other Parts: C25D1(n= 3, 55) | Pain in Other Parts: C26D1(n= 2, 50) | Pain in Other Parts: C27D1(n= 3, 49) | Pain in Other Parts: C28D1(n= 2, 44) | Pain in Other Parts: C29D1(n= 2, 36) | Pain in Other Parts: C30D1(n= 1, 30) | Pain in Other Parts: C31D1(n= 0, 23) | Pain in Other Parts: C32D1(n= 0, 23) | Pain in Other Parts: C33D1(n= 0, 15) | Pain in Other Parts: C34D1(n= 0, 14) | Pain in Other Parts: C35D1(n= 0, 10) | Pain in Other Parts: C36D1(n= 0, 8) | Pain in Other Parts: C37D1(n= 0, 5) | Pain in Other Parts: C38D1(n= 0, 2) | Pain in Other Parts: EOT(n= 250, 226) | Pain in Other Parts: Pro Week 6 Pd(n= 0,1) | Pain in Other Parts: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 27.94 | 27.76 | 25.87 | 23.45 | 22.32 | 21.50 | 24.63 | 18.35 | 21.48 | 21.57 | 20.05 | 16.67 | 19.76 | 22.03 | 19.18 | 21.90 | 22.22 | 22.10 | 24.58 | 21.17 | 21.26 | 18.82 | 18.82 | 19.67 | 16.97 | 18.67 | 14.29 | 15.15 | 21.30 | 16.67 | 11.59 | 20.29 | 11.11 | 30.95 | 26.67 | 20.83 | 33.33 | 0.00 | 32.01 | 0.00 | 66.67 |
,| Docetaxel | 27.52 | 29.58 | 22.87 | 21.48 | 21.21 | 22.78 | 23.05 | 24.10 | 18.18 | 15.15 | 14.71 | 8.97 | 17.65 | 18.52 | 6.67 | 20.51 | 15.15 | 13.33 | 18.52 | 25.93 | 12.50 | 20.83 | 20.83 | 26.67 | 11.11 | 16.67 | 11.11 | 0.00 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 30.80 | NA | 83.33 |
EORTC QLQ-LC13 Questionnaire Score: Peripheral Neuropathy
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for peripheral neuropathy. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Peripheral Neuropathy: Baseline (n= 386, 406) | Peripheral Neuropathy: C2D1(n= 335, 358) | Peripheral Neuropathy: C3D1(n= 250, 300) | Peripheral Neuropathy: C4D1(n= 221, 272) | Peripheral Neuropathy: C5D1(n= 165, 235) | Peripheral Neuropathy: C6D1(n= 147, 221) | Peripheral Neuropathy: C7D1(n= 86, 185) | Peripheral Neuropathy: C8D1(n=70, 167) | Peripheral Neuropathy: C9D1(n= 50, 150) | Peripheral Neuropathy: C10D1(n= 47, 143) | Peripheral Neuropathy: C11D1(n= 37, 129) | Peripheral Neuropathy: C12D1(n= 30, 129) | Peripheral Neuropathy: C13D1(n= 19, 121) | Peripheral Neuropathy: C14D1(n= 18, 119) | Peripheral Neuropathy: C15D1(n= 15, 110) | Peripheral Neuropathy: C16D1(n= 13, 105) | Peripheral Neuropathy: C17D1(n= 11, 95) | Peripheral Neuropathy: C18D1(n= 10, 90) | Peripheral Neuropathy: C19D1(n= 9, 82) | Peripheral Neuropathy: C20D1(n= 9, 78) | Peripheral Neuropathy: C21D1(n= 9, 73) | Peripheral Neuropathy: C22D1(n= 7, 66) | Peripheral Neuropathy: C23D1(n= 8, 64) | Peripheral Neuropathy: C24D1(n= 5, 62) | Peripheral Neuropathy: C25D1(n= 3, 58) | Peripheral Neuropathy: C26D1(n= 2, 53) | Peripheral Neuropathy: C27D1(n= 3, 50) | Peripheral Neuropathy: C28D1(n= 2, 46) | Peripheral Neuropathy: C29D1(n= 2, 38) | Peripheral Neuropathy: C30D1(n= 1, 31) | Peripheral Neuropathy: C31D1(n= 0, 24) | Peripheral Neuropathy: C32D1(n= 0, 23) | Peripheral Neuropathy: C33D1(n= 0, 16) | Peripheral Neuropathy: C34D1(n= 0, 14) | Peripheral Neuropathy: C35D1(n= 0, 11) | Peripheral Neuropathy: C36D1(n= 0, 8) | Peripheral Neuropathy: C37D1(n= 0, 5) | Peripheral Neuropathy: C38D1(n= 0, 2) | Peripheral Neuropathy: EOT(n= 262, 244) | Peripheral Neuropathy: Pro Week 6 Pd(n= 0,1) | Peripheral Neuropathy: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 19.21 | 20.02 | 17.78 | 17.77 | 18.44 | 17.50 | 18.02 | 17.56 | 15.78 | 18.18 | 17.05 | 17.57 | 17.91 | 17.09 | 17.58 | 17.14 | 19.30 | 18.15 | 20.33 | 17.52 | 18.72 | 15.66 | 20.31 | 20.43 | 18.39 | 20.13 | 19.33 | 19.57 | 19.30 | 20.43 | 23.61 | 18.84 | 22.92 | 19.05 | 15.15 | 8.33 | 26.67 | 16.67 | 19.54 | 66.67 | 33.33 |
,| Docetaxel | 19.26 | 25.57 | 25.60 | 28.05 | 29.29 | 31.97 | 31.01 | 35.24 | 36.00 | 36.17 | 27.93 | 30.00 | 26.32 | 25.93 | 24.44 | 20.51 | 21.21 | 23.33 | 14.81 | 22.22 | 29.63 | 23.81 | 16.67 | 13.33 | 11.11 | 16.67 | 11.11 | 0.00 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 31.81 | NA | 50.00 |
EORTC QLQ-LC13 Questionnaire Score: Sore Mouth
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for sore mouth. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Sore Mouth: Baseline (n= 387, 404) | Sore Mouth: C2D1(n= 335, 357) | Sore Mouth: C3D1(n= 252, 297) | Sore Mouth: C4D1(n= 219, 270) | Sore Mouth: C5D1(n= 165, 234) | Sore Mouth: C6D1(n= 148, 218) | Sore Mouth: C7D1(n= 87, 185) | Sore Mouth: C8D1(n=70, 166) | Sore Mouth: C9D1(n= 50, 151) | Sore Mouth: C10D1(n= 47, 143) | Sore Mouth: C11D1(n= 37, 130) | Sore Mouth: C12D1(n= 30, 129) | Sore Mouth: C13D1(n= 19, 121) | Sore Mouth: C14D1(n= 18, 119) | Sore Mouth: C15D1(n= 15, 110) | Sore Mouth: C16D1(n= 13, 106) | Sore Mouth: C17D1(n= 11, 95) | Sore Mouth: C18D1(n= 10, 90) | Sore Mouth: C19D1(n= 9, 82) | Sore Mouth: C20D1(n= 9, 78) | Sore Mouth: C21D1(n= 9, 73) | Sore Mouth: C22D1(n= 8, 67) | Sore Mouth: C23D1(n= 8, 64) | Sore Mouth: C24D1(n= 5, 62) | Sore Mouth: C25D1(n= 3, 57) | Sore Mouth: C26D1(n= 3, 53) | Sore Mouth: C27D1(n= 3, 50) | Sore Mouth: C28D1(n= 2, 46) | Sore Mouth: C29D1(n= 2, 38) | Sore Mouth: C30D1(n= 1, 31) | Sore Mouth: C31D1(n= 0, 24) | Sore Mouth: C32D1(n= 0, 23) | Sore Mouth: C33D1(n= 0, 16) | Sore Mouth: C34D1(n= 0, 14) | Sore Mouth: C35D1(n= 0, 11) | Sore Mouth: C36D1(n= 0, 8) | Sore Mouth: C37D1(n= 0, 5) | Sore Mouth: C38D1(n= 0, 2) | Sore Mouth: EOT(n= 265, 243) | Sore Mouth: Pro Week 6 Pd(n= 0,1) | Sore Mouth: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 4.95 | 7.10 | 5.61 | 4.81 | 4.27 | 4.13 | 5.59 | 5.02 | 3.09 | 3.96 | 3.33 | 4.65 | 5.23 | 5.32 | 4.24 | 3.77 | 6.32 | 3.70 | 4.47 | 5.56 | 7.76 | 6.47 | 6.25 | 5.38 | 3.51 | 6.92 | 4.00 | 4.35 | 3.51 | 4.30 | 4.17 | 4.35 | 4.17 | 9.52 | 6.06 | 4.17 | 13.33 | 0.00 | 7.00 | 66.67 | 0.00 |
,| Docetaxel | 5.68 | 15.52 | 14.29 | 14.00 | 11.31 | 13.29 | 9.20 | 8.57 | 6.00 | 7.09 | 4.50 | 2.22 | 1.75 | 3.70 | 0.00 | 0.00 | 3.03 | 3.33 | 0.00 | 0.00 | 0.00 | 4.17 | 4.17 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 11.57 | NA | 16.67 |
Percentage of Participants With Objective Response as Determined Using RECIST v1.1: PP-ITT
Objective response is defined as a complete response (CR) or partial response (PR) as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. 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 less than [<] 10 mm). No new lesions. At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR. No new lesions. (NCT02008227)
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel | 13.4 |
| Atezolizumab | 13.6 |
Minimum Observed Serum Atezolizumab Concentration (Cmin)
(NCT02008227)
Timeframe: Predose (Hr 0) on Day 1 of Cycles 1, 2, 3, 4, 8, 16, 24, 32, EOT (approximately 2.25 years); 120 days after EOT (approximately 2.25 years) (1 Cycle=21 days)
| Intervention | mcg/mL (Mean) |
|---|
| C1D1 (n= 593) | C2D1 (n= 534) | C3D1 (n= 445) | C4D1 (n= 405) | C8D1 (n= 222) | C16D1 (n= 132) | C24D1 (n= 63) | C32D1 (n= 11) | EOT (n= 347) | 120 days after EOT (n= 124) |
|---|
| Atezolizumab | 2.59 | 83.2 | 130 | 158 | 205 | 226 | 250 | 277 | 144 | 10.4 |
Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms, Using the European Organization for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ) Lung Cancer Supplemental Module 13 (LC13)
TTD in patient-reported lung cancer symptoms (pain in chest or in arm/shoulder, dyspnea, or cough) 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 symptoms. A >/=10-point change in the score perceived by participants was considered as clinically significant. 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. Scale score range: 0 to 100. Higher symptom score = greater degree of symptom severity. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years) (1 Cycle = 21 days)
| Intervention | Months (Median) |
|---|
| Pain in Chest | Cough | Dyspnea | Arm/Shoulder Pain |
|---|
| Atezolizumab | 18.0 | 5.5 | 1.8 | 8.3 |
,| Docetaxel | 8.3 | 5.6 | 2.1 | 6.2 |
EORTC QLQ-LC13 Questionnaire Score: Alopecia
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 experienced during past 1 week. The 13 questions comprised 1 multi-item scale for dyspnea and 10 single-item symptoms and side effects (coughing, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts. Response range: (1) not at all to (4) very much. Scores for each item were transformed to 0 to 100, where higher symptom score = greater degree of symptoms. Results have been reported for alopecia. (NCT02008227)
Timeframe: Day 1 of each treatment Cycle up to EOT (up to approximately 2.25 years); 6 week following PD ( Pro Week 6 Pd) (up to approximately 2.25 years); survival follow-up-1 (up to approximately 2.25 years) (1 Cycle= 21 days)
| Intervention | Units on a scale (Mean) |
|---|
| Alopecia: Baseline (n= 384, 405) | Alopecia: C2D1(n= 332, 357) | Alopecia: C3D1(n= 248, 300) | Alopecia: C4D1(n= 219, 270) | Alopecia: C5D1(n= 163, 234) | Alopecia: C6D1(n= 147, 220) | Alopecia: C7D1(n= 87, 186) | Alopecia: C8D1(n= 70, 166) | Alopecia: C9D1(n= 47, 150) | Alopecia: C10D1(n= 45, 142) | Alopecia: C11D1(n= 36, 130) | Alopecia: C12D1(n= 29, 129) | Alopecia: C13D1(n= 19, 121) | Alopecia: C14D1(n= 18, 119) | Alopecia: C15D1(n= 16, 110) | Alopecia: C16D1(n= 12, 105) | Alopecia: C17D1(n= 11, 95) | Alopecia: C18D1(n= 9, 90) | Alopecia: C19D1(n= 8, 81) | Alopecia: C20D1(n= 9, 78) | Alopecia: C21D1(n= 9, 73) | Alopecia: C22D1(n= 7, 67) | Alopecia: C23D1(n= 8, 64) | Alopecia: C24D1(n= 5, 62) | Alopecia: C25D1(n= 2, 58) | Alopecia: C26D1(n= 2, 53) | Alopecia: C27D1(n= 3, 50) | Alopecia: C28D1(n= 2, 46) | Alopecia: C29D1(n= 2, 38) | Alopecia: C30D1(n= 1, 31) | Alopecia: C31D1(n= 0, 24) | Alopecia: C32D1(n= 0, 23) | Alopecia: C33D1(n= 0,16) | Alopecia: C34D1(n= 0, 14) | Alopecia: C35D1(n= 0, 11) | Alopecia: C36D1(n= 0, 8) | Alopecia: C37D1(n= 0, 5) | Alopecia: C38D1(n= 0, 2) | Alopecia: EOT(n= 261, 243) | Alopecia: Pro Week 6 Pd(n= 0,1) | Alopecia: Survival FU 1 (n= 2, 1) |
|---|
| Atezolizumab | 14.32 | 6.63 | 7.44 | 7.41 | 6.41 | 7.88 | 5.91 | 6.63 | 5.11 | 3.76 | 3.08 | 4.91 | 6.06 | 5.60 | 7.27 | 7.30 | 9.47 | 8.89 | 10.29 | 8.55 | 9.59 | 9.45 | 11.46 | 8.06 | 9.77 | 9.43 | 9.33 | 6.52 | 8.77 | 10.75 | 9.72 | 7.25 | 8.33 | 9.52 | 6.06 | 4.17 | 6.67 | 0.00 | 6.58 | 100.00 | 66.67 |
,| Docetaxel | 13.89 | 60.44 | 56.72 | 52.36 | 56.65 | 54.42 | 52.11 | 48.57 | 48.23 | 49.63 | 47.22 | 36.78 | 42.11 | 29.63 | 33.33 | 27.78 | 21.21 | 22.22 | 25.00 | 44.44 | 22.22 | 9.52 | 29.17 | 13.33 | 0.00 | 0.00 | 33.33 | 0.00 | 0.00 | 0.00 | NA | NA | NA | NA | NA | NA | NA | NA | 53.51 | NA | 100.00 |
Percentage of Participants With Disease Progression (PD) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) or Death: PP-ITT
PD: 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 millimeters (mm), or presence of new lesions. (NCT02008227)
Timeframe: Baseline up to PD or Death (up to approximately 2.25 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel | 88.2 |
| Atezolizumab | 89.4 |
Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) Against Atezolizumab
(NCT02008227)
Timeframe: Baseline up to approximately 2.25 years (assessed at predose [Hour {Hr} 0] on Day 1 of Cycles 1, 2, 3, 4, 8, 16, then every 8 cycles up to end of treatment (EOT) [approximately 2.25 years]; 120 days after EOT [approximately 2.25 years] [1 Cycle=21 days])
| Intervention | Percentage of Participants (Number) |
|---|
| Atezolizumab | 30.4 |
Percentage of Participants With Objective Response as Determined Using RECIST v1.1: SP-ITT
Objective response is defined as a complete response (CR) or partial response (PR) as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. 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 less than [<] 10 mm). No new lesions. At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR. No new lesions. (NCT02008227)
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel | 11.8 |
| Atezolizumab | 13.7 |
Percentage of Participants With Objective Response as Determined Using RECIST v1.1: TC1/2/3 or IC1/2/3 Subgroup of PP
Objective response is defined as a CR or PR as determined by the Investigator using RECIST v1.1 on 2 consecutive occasions at least 6 weeks apart. 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. At least a 30% decrease in the sum of the diameters of all target and all new measurable lesions, taking as reference the baseline sum of diameters, in the absence of CR. No new lesions. (NCT02008227)
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.25 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel | 16.2 |
| Atezolizumab | 17.8 |
Percentage of Participants With PD as Determined by Investigator Using RECIST v1.1 or Death: TC1/2/3 or IC1/2/3 Subgroup of PP
PD: 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, or presence of new lesions. (NCT02008227)
Timeframe: Baseline up to PD or Death (up to approximately 2.25 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel | 86.9 |
| Atezolizumab | 89.6 |
PFS as Determined by Investigator Using RECIST v1.1: SP-ITT
PFS is defined as the time between the date of randomization and the date of first documented PD or death, whichever occurs first. Participants who are alive and have not experienced PD at the time of analysis were censored at the time of the last tumor assessment. Participants with no post-baseline tumor assessment were censored at the randomization date plus 1 day. PD: 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, or presence of new lesions. (NCT02008227)
Timeframe: Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 2.87 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 3.8 |
| Atezolizumab | 2.7 |
OS: TC3 or IC3 Subgroup of SP
OS duration is defined as the difference in time from the date of randomization to the date of death due to any cause. Data for participants who were not reported as having died at the time of analysis were censored at the date they were last known to be alive. Participants who had no post-baseline information were censored at the date of randomization plus 1 day. OS was estimated using KM methodology. (NCT02008227)
Timeframe: Baseline until death due to any cause (up to approximately 2.87 years)
| Intervention | Months (Median) |
|---|
| Docetaxel | 9.7 |
| Atezolizumab | 20.5 |
OS During Second-Line of Treatment
The OS during second-line therapy was defined as the time from the start of second-line therapy (failure of first-line therapy) until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS during second-line therapy was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method. (NCT02019277)
Timeframe: From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)
| Intervention | months (Median) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 21.29 |
Percentage of Participants Who Died Due to Any Cause
Percentage of participants who died due to any cause during the study was reported. (NCT02019277)
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 18.0 |
Percentage of Participants Who Died During Receiving Second-Line of Treatment
Percentage of participants who died from any cause during second-line of treatment was reported. (NCT02019277)
Timeframe: From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 30.0 |
Percentage of Participants With AEs Leading to Premature Discontinuation of Investigational Medicinal Products (IMPs)
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Percentage of participants with AEs leading to premature discontinuation of IMPs (pertuzumab and trastuzumab) was reported. AEs included both SAEs and non-SAEs. The 95% CI was computed using Clopper-Pearson method. (NCT02019277)
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 12.0 |
Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
BOR was defined as a confirmed CR or PR. All measurable lesions up to a maximum of 2 lesions per organ and 5 in total were identified as target lesions (TLs) and recorded at baseline. A sum of the diameters (longest for non-nodal lesions, short axis [SA] for nodal lesions) for all TLs was calculated as baseline sum of diameters (SD). All other lesions (or sites of disease) were identified as non-TLs and were recorded at baseline. CR was defined as the disappearance of all TLs and SA reduction to less than (<) 10 millimeter (mm) for nodal TLs/ non-TLs. PR was defined as greater than or equal to (>/=) 30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. The 95% CI was computed using Clopper-Pearson method. (NCT02019277)
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 73.3 |
Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Below 50%
LVEF was assessed using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scans. Percentage of participants with LVEF below 50% at any time during the study was reported. (NCT02019277)
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 8.0 |
Percentage of Participants With PD (Assessed According to RECIST Version 1.1) or Death Due to Any Cause
For TLs, PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD, taking as reference the smallest SD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs. (NCT02019277)
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 60.0 |
Progression-free Survival (PFS) Assessed According to RECIST Version 1.1
PFS was defined as the time from start of treatment until first documented PD or death from any cause, whichever occurred first. Participants without PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment data after the baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median PFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method. (NCT02019277)
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
| Intervention | months (Median) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 17.02 |
Number of Participants Receiving Second-Line Treatment by Treatment Type
Second-line anti-cancer treatment was initiated after disease progression on first-line therapy. Number of participants who started second-line of treatment by treatment type was reported. Participants who received combination treatment were counted for each treatment type. (NCT02019277)
Timeframe: Baseline up to approximately 35 months
| Intervention | participants (Number) |
|---|
| Capecitabine | Cyclophosphamide | Denosumab | Doxorubicin | Epirubicin | Eribulin | Fluorouracil | Lapatinib | Nanoparticle Paclitaxel | Paclitaxel | Pertuzumab | Trastuzumab | Trastuzumab Emtansine | Vinorelbine |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 8 | 2 | 2 | 1 | 1 | 1 | 1 | 4 | 1 | 4 | 5 | 13 | 10 | 1 |
Percentage of Participants With Adverse Events (AEs) and Serious AEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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. Percentage of participants with AEs and SAEs was reported. AEs included both SAEs and non-SAEs. The 95% confidence interval (CI) was computed using Clopper-Pearson method. (NCT02019277)
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)
| Intervention | percentage of participants (Number) |
|---|
| AEs | SAEs |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 100.0 | 54.0 |
Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of AEs were graded according to NCI CTCAE version 4.0 on a 5-point scale: Grade 1=Mild, intervention not indicated; Grade 2=Moderate, local or noninvasive intervention indicated; Grade 3=Severe or medically significant but not immediately life-threatening; Grade 4= Life-threatening consequences, urgent intervention indicated; and Grade 5=Death related to AE. Percentage of participants with AEs by maximum severity grades was reported. (NCT02019277)
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 4.0 | 32.0 | 50.0 | 12.0 | 2.0 |
Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
NYHA functional classification includes: Class I (no limitation in physical activity; ordinary physical activity does not cause fatigue, breathlessness or palpitation), Class II (slight limitation of physical activity; ordinary physical activity results in fatigue, palpitation, breathlessness or angina pectoris), Class III (marked limitation of physical activity; less than ordinary activity will lead to symptomatically 'moderate' heart failure) and Class IV (inability to carry out any physical activity without discomfort; symptoms of congestive cardiac failure are present even at rest). Percentage of participants with AEs suspected to be of cardiac origin by maximum NYHA classification was reported. (NCT02019277)
Timeframe: Baseline up to 28 days after last study drug administration (up to 36 months)
| Intervention | percentage of participants (Number) |
|---|
| Class I | Class II | Class III | Class IV |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 6.0 | 4.0 | 2.0 | 0.0 |
Overall Survival (OS)
The OS was defined as the time from the start of treatment until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method. (NCT02019277)
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
| Intervention | months (Median) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | NA |
Event-free Survival (EFS) Assessed According to RECIST Version 1.1
EFS was defined as the time from the start of treatment until the first documented initiation of non-protocol-specified treatment for metastatic breast cancer, PD, or death from any cause, whichever occurred first. Participants without treatment change, PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment after baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median EFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method. (NCT02019277)
Timeframe: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
| Intervention | months (Median) |
|---|
| Trastuzumab, Pertuzumab, and Taxane | 17.02 |
Time To Progression (TTP)
Tumor assessments were performed until disease progression in order to evaluate the TTP. TTP is defined as the time from the date of the first dose to the first date of objectively determined progressive disease. For patients not known to have objectively-determined progressive disease, TTP will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression, TTP will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation systemic anticancer therapy. (NCT02027376)
Timeframe: Through study treatment, an average of 2 months
| Intervention | days (Median) |
|---|
| LDE225 (Sonidegib) 400mg in Combination With Docetaxel | 42.0 |
| LDE225 (Sonidegib) 600mg in Combination With Docetaxel | 42.5 |
| LDE225 (Sonidegib) 800mg in Combination With Docetaxel | 188 |
Docetaxel Clearance on Cycle 1 and Cycle 2 (Pharmacokinetics (PK))
PK sampling of docetaxel was performed on Day 1 of Cycle 1 and 2 of treatment and docetaxel concentrations. Blood samples were collected into ethylenediaminetetraacetic acid (EDTA) K3 tubes and after plasma separation by centrifugation were stored at -70 degrees Celsius until analysis. (NCT02027376)
Timeframe: Cycles 1 and 2
| Intervention | L/h (Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| LDE225 (Sonidegib) in Combination With Docetaxel | 48.8 | 42.7 |
Changes in QT/QTc From Baseline and Cycle 3 ECG Values.
The QTc intervals have been characterized by comparing QTc at baseline (QTc interval measured in milliseconds (msec) by Fridericia's formula) and at cycle 3 pre-dose, 1 hour post-dose, 2 hours post-dose, 4 hours post-dose and 6 hours post-dose. (NCT02027376)
Timeframe: From baseline to cycle 3
| Intervention | milliseconds (Mean) |
|---|
| Cycle 3, Predose | Cycle 3, 1 hour | Cycle 3, 2 hours | Cycle 3, 4 hours | Cycle 3, 6 hours |
|---|
| LDE225 (Sonidegib) in Combination With Docetaxel | 28.5 | 4.5 | 9.5 | 2.8 | 4.3 |
The Number of Participants Who Experienced Adverse Events (AE)
Safety was assessed by standard clinical and laboratory tests [vital signs including blood pressure, pulse and body temperature, triplicate 12-lead ECGs at screening and on day 1 of cycle 3, blood tests including hematology (hemoglobin, platelets count, red blood cells (RBC), white blood cells (WBC) with differential count and serum chemistry (serum creatinine, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), creatine phosphokinase (CPK))]. Adverse events grade were defined by the NCI CTCAE v4.0. (NCT02027376)
Timeframe: Through study treatment, an average of 2 months
| Intervention | number of participants with AE (Number) |
|---|
| LDE225 (Sonidegib) 400mg in Combination With Docetaxel | 5 |
| LDE225 (Sonidegib) 600mg in Combination With Docetaxel | 4 |
| LDE225 (Sonidegib) 800mg in Combination With Docetaxel | 3 |
Recommended Phase II Dose (RP2D) of LDE225 (Sonidegib) in Combination With Docetaxel
The RP2D was decided by the investigators taken into consideration the information obtained in the study and based on the MTD. To define the RP2D, information about toxicity observed during the full treatment were taken into consideration (relative dose intensity and toxicity observed). (NCT02027376)
Timeframe: Through study treatment, an average of 2 months
| Intervention | mg (Number) |
|---|
| LDE225 (Sonidegib) in Combination With Docetaxel | 800 |
Objective Response Rate (ORR)
Tumor response was assessed using RECIST 1.1 criteria. The best response across all treatment was recorded. ORR is defined as the percentage of patients with a complete or partial response out of the patients who had measurable disease at baseline. (NCT02027376)
Timeframe: Through study treatment, an average of 2 months
| Intervention | Participants (Count of Participants) |
|---|
| LDE225 (Sonidegib) 400mg in Combination With Docetaxel | 0 |
| LDE225 (Sonidegib) 600mg in Combination With Docetaxel | 0 |
| LDE225 (Sonidegib) 800mg in Combination With Docetaxel | 1 |
Maximum Tolerated Dose (MTD) of LDE225 (Sonidegib) in Combination With Docetaxel
MTD was determined by testing increasing doses of LDE225 on dose escalation cohorts 1 to 6 patients. MTD reflects the highest dose tested in which a DLT is experienced by 0 out of 3 or 1 out of 6 patients among the dose levels. (NCT02027376)
Timeframe: Through study treatment, an average of 2 months
| Intervention | mg (Number) |
|---|
| LDE225 (Sonidegib) in Combination With Docetaxel | 800 |
LDE225 (Sonidegib) Trough Concentration (Pharmacokinetics (PK))
To evaluate the effect of LDE225 on the docetaxel PK, the main pharmacokinetic parameters of docetaxel were estimated on Day 1 of Cycles 1 and 2 of treatment, and compared between them. PK parameters were estimated by non-compartmental approach using Phoenix® WinNonlin® software (version 7.0). In the case of the effect of docetaxel on the LDE225 PK, since patients were always under both drugs at all the assessed PK profiles, the trough LDE225 concentrations obtained in our study were compared with those simulated from a previous developed PK model from LDE225 given as monotherapy. Therefore, a population PK model of LDE225 reported in the literature and developed in healthy subjects and patients with advanced solid tumors was implemented in NONMEN version 7.3 program and Monte-Carlo simulations of LDE225 concentrations after the same doses than those of our study, were performed. (NCT02027376)
Timeframe: Up to cycle 2
| Intervention | mg/L (Mean) |
|---|
| LDE225 (Sonidegib) 400mg in Combination With Docetaxel | 0.398 |
| LDE225 (Sonidegib) 600mg in Combination With Docetaxel | 0.392 |
| LDE225 (Sonidegib) 800mg in Combination With Docetaxel | 0.727 |
Incidence Rate of DLT Within the First Two Cycles of LDE225 (Sonidegib) in Combination With Docetaxel
DLT was defined as the occurrence of any of the following adverse events or abnormal laboratory values (graded according to the NCI-CTCAE version 4.0) assessed as possibly, probably or definitively related to study drugs, occurring within the first two cycles of treatment: Neutropenia grade 4 lasting more than one week, febrile neutropenia, thrombocytopenia grade 3 with bleeding more than grade 2, thrombocytopenia grade 4, Increased plasma creatinine phosphokinase (CK) grade 3-4, any non-hematologic grade 4 toxicity, or grade 3 toxicity except nausea and vomiting, Grade 2 GI toxicity (except nausea and vomiting) lasting more than 2 weeks, Inability to resume dosing for cycles 2 or 3 at the current dose level within 14 days, due to treatment-related toxicity. Dose reductions in cycles 1 and 2 will be considered a DLT (NCT02027376)
Timeframe: Up to cycle 2
| Intervention | Participants (Count of Participants) |
|---|
| LDE225 (Sonidegib) 400mg in Combination With Docetaxel | 0 |
| LDE225 (Sonidegib) 600mg in Combination With Docetaxel | 0 |
| LDE225 (Sonidegib) 800mg in Combination With Docetaxel | 0 |
Overall Survival (OS)
OS was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Median OS time was calculated using Kaplan-Meier (KM) method. (NCT02105636)
Timeframe: From date of randomization to date of death (Up to approximately 18 months)
| Intervention | Months (Median) |
|---|
| Nivolumab 3mg/kg | 7.49 |
| Investigators Choice | 5.06 |
Investigator-Assessed Objective Response Rate (ORR)
ORR was defined as the percentage of randomized participants who achieved a best response of complete response (CR) or partial response (PR) using the RECIST1.1 criteria as per investigator assessment. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. (NCT02105636)
Timeframe: From date of randomization to date of disease progression or study drug is discontinued, whichever occurs first (Up to approximately 87 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Nivolumab 3mg/kg | 13.3 |
| Investigators Choice | 5.8 |
Investigator-Assessed Progression-Free Survival (PFS)
"PFS was defined as the time between the date of randomization and the first date of documented progression, as determined by the investigator (as per Response Evaluation Criteria In Solid Tumors (RECIST1.1)), or death due to any cause, whichever occurs first. Progressive Disease: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must demonstrate an absolute increase of at least 5mm. Participants who:~Die without a reported progression were considered to have progressed on the date of their death.~Did not progress or die were censored on the date of their last evaluable tumor assessment.~Without any on study tumor assessments and did not die were censored on their date of randomization.~Received subsequent systemic anti-cancer therapy prior to documented progression were censored at the date of the last tumor assessment prior to the initiation of the new therapy." (NCT02105636)
Timeframe: From date of randomization to date of disease progression or death, whichever occurs first (Up to approximately 87 months)
| Intervention | Months (Median) |
|---|
| Nivolumab 3mg/kg | 2.04 |
| Investigators Choice | 2.33 |
Overall Survival (OS) - Extended Collection
"OS was defined as the time from randomization to the date of death from any cause. Participants were censored at the date they were last known to be alive and at the date of randomization if they were randomized but had no follow-up. Median OS time was calculated using Kaplan-Meier (KM) method.~Note: This outcome measure represents an updated version of the primary endpoint to include additional data collection that has occurred after the primary completion date. (Assessments were made until 10-Sep-2021)" (NCT02105636)
Timeframe: From date of randomization to date of death (Up to approximately 87 months)
| Intervention | Months (Median) |
|---|
| Nivolumab 3mg/kg | 7.72 |
| Investigators Choice | 5.06 |
Time to Progression (TTP)
Evaluate immune-related TTP (irTTP) and also TTP (Time to Progression) by RECIST (NCT02117024)
Timeframe: Up to 3 years
| Intervention | Days (Median) |
|---|
| immune-related TTP (irTTP) | Time to Progression (TTP) |
|---|
| Chemotherapy Alone | 71.0 | 73.5 |
,| Viagenpumatucel-L Plus Metronomic Cyclophosphamide | 67.0 | 67.5 |
Survival at 6 Months
Evaluate the proportion of patients who are alive at 6 months following randomization (NCT02117024)
Timeframe: 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Viagenpumatucel-L Plus Metronomic Cyclophosphamide | 21 |
| Chemotherapy Alone | 17 |
Overall Survival (OS)
"Overall survival (OS) calculated as the duration of survival from the date of randomization to the date of death from any cause, or was censored on the date the patient was last known to be alive.~Survival time was calculated from the randomization date up to the date of death,or censored on the date that the patient was last known to be alive (last available visit date) utilizing Kaplan-Meier Estimate of Overall Survival Ending Events" (NCT02117024)
Timeframe: Up to 3 years
| Intervention | Days (Median) |
|---|
| Viagenpumatucel-L Plus Metronomic Cyclophosphamide | 176 |
| Chemotherapy Alone | 372 |
Survival at 12 Months
Evaluate the proportion of patients who are alive at 12 months following randomization (NCT02117024)
Timeframe: 12 months
| Intervention | Participants (Count of Participants) |
|---|
| Viagenpumatucel-L Plus Metronomic Cyclophosphamide | 8 |
| Chemotherapy Alone | 11 |
Frequency of Adverse Events: Number of Participants With Treatment-Emergent Adverse Events (TEAE)
Evaluate the safety of the combination of viagenpumatucel-L and low-dose cyclophosphamide by frequency of Treatment-Emergent Adverse Events (NCT02117024)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| At least one TEAE | At least one severe TEAE | At least one treatment-related TEAE | At least one SAE | Fatal TEAE | At least one TEAE Leading to Tx Discontinuation | At least one TEAE Leading to a Dose Reduction |
|---|
| Chemotherapy Alone | 20 | 11 | 15 | 8 | 0 | 2 | 2 |
,| Viagenpumatucel-L Plus Metronomic Cyclophosphamide | 41 | 25 | 32 | 17 | 7 | 7 | 0 |
Progression-Free Survival (PFS)
Evaluate immune-related PFS (irPFS) and PFS by RECIST (Response Evaluation Criteria for Solid Tumors) (NCT02117024)
Timeframe: Up to 3 years
| Intervention | Days (Median) |
|---|
| immune-related PFS (irPFS) | Progression Free Survival (PFS) |
|---|
| Chemotherapy Alone | 190.0 | 190.0 |
,| Viagenpumatucel-L Plus Metronomic Cyclophosphamide | 76.0 | 70.0 |
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
| Intervention | h*ng/mL (Geometric Mean) |
|---|
| Part A: MLN4924 8 mg/m^2 | 450 |
| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 498 |
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
| Intervention | h*ng/mL (Geometric Mean) |
|---|
| Part A: MLN4924 8 mg/m^2 | 465 |
| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 585 |
| Part A: MLN4924 15 mg/m^2 | 798 |
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 1060 |
| Part A: MLN4924 20 mg/m^2 | 1120 |
| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 1130 |
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
| Intervention | hour*nanogram per milliliter (h*ng/mL) (Geometric Mean) |
|---|
| Part A: MLN4924 8 mg/m^2 | 445 |
| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 491 |
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
| Intervention | h*ng/mL (Geometric Mean) |
|---|
| Part A: MLN4924 8 mg/m^2 | 459 |
| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 571 |
| Part A: MLN4924 15 mg/m^2 | 793 |
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 1030 |
| Part A: MLN4924 20 mg/m^2 | 1110 |
| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 1140 |
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
| Intervention | nanogram per milliliter (ng/mL) (Geometric Mean) |
|---|
| Part A: MLN4924 8 mg/m^2 | 51.6 |
| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 51.0 |
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
| Intervention | ng/mL (Geometric Mean) |
|---|
| Part A: MLN4924 8 mg/m^2 | 59.1 |
| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 66.8 |
| Part A: MLN4924 15 mg/m^2 | 121 |
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 193 |
| Part A: MLN4924 20 mg/m^2 | 178 |
| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 137 |
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)
| Intervention | months (Mean) |
|---|
| Part B: MLN4924 + Docetaxel | 4.07 |
| Part B: MLN4924 + Carboplatin or Paclitaxel | 8.46 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| TEAE | SAE |
|---|
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 6 | 2 |
,| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 18 | 5 |
,| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 13 | 3 |
,| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 13 | 3 |
,| Part B: MLN4924 + Carboplatin or Paclitaxel | 13 | 6 |
,| Part B: MLN4924 + Docetaxel | 23 | 14 |
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
| Intervention | participants (Number) |
|---|
| Grade 1 AE: 5 < 10% decrease from baseline | Grade 2 AE: 10 - <20% decrease from baseline | Grade 3 AE: >=20% decrease from baseline |
|---|
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 0 | 0 | 0 |
,| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 1 | 1 | 0 |
,| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 0 | 0 | 0 |
,| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 0 | 0 | 0 |
,| Part B: MLN4924 + Carboplatin or Paclitaxel | 1 | 0 | 0 |
,| Part B: MLN4924 + Docetaxel | 1 | 0 | 0 |
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
| Intervention | hour (Median) |
|---|
| Day 1 | Day 8 |
|---|
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 1.24 | 1.03 |
,| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 1.05 | 1.13 |
,| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 1.04 | 1.21 |
,| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 1.02 | 1.50 |
Part A: Blood to Plasma (B/P) Concentration Ratio for MLN4924
(NCT02122770)
Timeframe: Day 1 up to 24 hours post infusion
| Intervention | Ratio (Geometric Mean) |
|---|
| End of infusion | 2 hours post infusion | 8 hours post infusion | 24 hours post infusion |
|---|
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 55.2 | 66.5 | 70.7 | 66.3 |
,| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 35.1 | 48.8 | 56.7 | 58.0 |
,| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 51.1 | 69.2 | 71.1 | 71.9 |
,| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 43.7 | 54.7 | 73.7 | 67.6 |
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
| Intervention | liter per hour (L/h) (Geometric Mean) |
|---|
| Day 1 | Day 8 |
|---|
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 35.2 | 26.5 |
,| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 35.8 | 35.5 |
,| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 31.7 | 28.6 |
,| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 29.2 | 23.2 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Part B: MLN4924 + Docetaxel | 10.5 |
| Part B: MLN4924 + Carboplatin or Paclitaxel | 22.2 |
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
| Intervention | Liter (L) (Geometric Mean) |
|---|
| Day 1 | Day 8 |
|---|
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 494 | 421 |
,| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 511 | 550 |
,| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 503 | 477 |
,| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 445 | 445 |
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
| Intervention | hour (Geometric Mean) |
|---|
| Day 1 | Day 8 |
|---|
| Part A: MLN4924 15 mg/m^2 + Itraconazole 200 mg | 9.74 | 11.0 |
,| Part A: MLN4924 20 mg/m^2 + Itraconazole 200 mg | 9.88 | 10.7 |
,| Part A: MLN4924 8 mg/m^2 + Fluconazole 400 mg | 11.0 | 11.6 |
,| Part A: MLN4924 8 mg/m^2 + Itraconazole 200 mg | 10.6 | 13.3 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| Washington University: Neoadjuvant Docetaxel and Carboplatin | 47 |
| Baylor: Neoadjuvant Docetaxel and Carboplatin | 11 |
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)
| Intervention | change in score (Mean) |
|---|
| PHYSICAL WELL-BEING SCORE | SOCIAL/FAMILY WELL-BEING SCORE | EMOTIONAL WELL-BEING SCORE | FUNCTIONAL WELL-BEING SCORE | FACT-G TOTAL SCORE | ADDITIONAL CONCERNS SCORE | FACT-H&N TOTAL SCORE | TRIAL OUTCOME INDEX SCORE |
|---|
| Chemotherapy Plus Radiation Therapy | -1.46 | -1.34 | 2.05 | -0.48 | -1.23 | 5.01 | 3.79 | 3.08 |
,| Chemotherapy Without Radiation | -1.64 | -2.34 | 1.60 | -1.70 | -4.08 | 3.63 | -0.46 | 0.29 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Chemotherapy Plus Radiation Therapy | 6 |
| Chemotherapy Without Radiation | 4 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Chemotherapy Plus Radiation Therapy | 14 |
| Chemotherapy Without Radiation | 11 |
Phase 1 - Maximum Tolerated Dose (MTD) of STI571
To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin, when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC. (NCT02127372)
Timeframe: After cycle 1, day 22
| Intervention | mg (Number) |
|---|
| Phase 1 | 400 |
Phase 2: 1 Year Survival
Phase II: Percentage of patients alive 1 year from the start of protocol treatment. (NCT02127372)
Timeframe: 1 year
| Intervention | percentage of participants (Number) |
|---|
| Phase 2 | 61 |
Phase II - Radiographic Response
"The percentage of patients with a complete or partial response.~Responses for the Phase II portion of the trial will be by Response Evaluation Criteria In Solid Tumors (RECIST) criteria as follows:~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, taking as reference the baseline sum LD." (NCT02127372)
Timeframe: After Cycle 6, approximately 18 weeks.
| Intervention | percentage of participants (Number) |
|---|
| Phase 2 | 25 |
Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin
To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC. (NCT02127372)
Timeframe: After cycle 1, day 22
| Intervention | mg/m2 (Number) |
|---|
| Docetaxel | Cisplatin |
|---|
| Phase 1 | 60 | 60 |
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
| Intervention | months (Median) |
|---|
| TCH + P | 3.02 |
| T-DM1 + P | 4.63 |
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.
| Intervention | mcg/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 + P | 80.4 | 71.7 | 79.1 | 79.1 | 70.4 | 73.1 | 73.0 | 82.6 |
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)
| Intervention | Percentage of Participants (Number) |
|---|
| TCH + P | 56.1 |
| T-DM1 + P | 44.4 |
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)
| Intervention | Probability (Number) |
|---|
| TCH + P | 91.99 |
| T-DM1 + P | 93.04 |
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
| Intervention | mcg/mL (Mean) |
|---|
| Trastuzumab (neoadjuvant period) | Trastuzumab (adjuvant period) |
|---|
| TCH + P | 45.8 | 21.8 |
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
| Intervention | Percentage of Participants (Number) |
|---|
| Cognitive Functioning | Physical Functioning | Role Functioning |
|---|
| T-DM1 + P | 42.4 | 40.0 | 47.8 |
,| TCH + P | 59.1 | 72.5 | 76.7 |
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
| Intervention | micrograms per milliliter (mcg/mL) (Mean) |
|---|
| Cycle 1 (neoadjuvant period) | Cycle 6 (neoadjuvant period) | Cycle 1 (adjuvant period) | Cycle 6 (adjuvant period) |
|---|
| TCH + P | 167 | 148 | 159 | 181 |
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
| Intervention | mcg/mL (Mean) |
|---|
| Trastuzumab emtansine (neoadjuvant) | Total Trastuzumab (neoadjuvant) | Trastuzumab emtansine (adjuvant) | Total Trastuzumab (adjuvant) |
|---|
| T-DM1 + P | 3.04 | 12.3 | 4.09 | 8.70 |
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
| Intervention | Percentage of Participants (Number) |
|---|
| Appetite Loss | Any Hair Loss | Systemic Therapy Side-Effects | Constipation | Diarrhea | Dyspnea | Fatigue | Nausea/Vomiting | Pain | Insomnia |
|---|
| T-DM1 + P | 47.8 | 40.5 | 75.1 | 32.7 | 50.7 | 31.2 | 68.8 | 43.9 | 36.6 | 30.2 |
,| TCH + P | 61.1 | 91.2 | 89.7 | 33.2 | 79.3 | 56.0 | 87.6 | 66.3 | 56.0 | 42.5 |
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)
| Intervention | Percentage of Participants (Number) |
|---|
| Q1: Not at all: Baseline | Q1: A little bit: Baseline | Q1: Somewhat: Baseline | Q1: Quite a bit: Baseline | Q1: Very much: Baseline | Q1: Not at all: Neoadjuvant Cycle 3 | Q1: A little bit: Neoadjuvant Cycle 3 | Q1: Somewhat: Neoadjuvant Cycle 3 | Q1: Quite a bit: Neoadjuvant Cycle 3 | Q1: Very much: Neoadjuvant Cycle 3 | Q1: Not at all: Neoadjuvant Cycle 5 | Q1: A little bit: Neoadjuvant Cycle 5 | Q1: Somewhat: Neoadjuvant Cycle 5 | Q1: Quite a bit: Neoadjuvant Cycle 5 | Q1: Very much: Neoadjuvant Cycle 5 | Q1: Not at all: Pre-Surgery | Q1: A little bit: Pre-Surgery | Q1: Somewhat: Pre-Surgery | Q1: Quite a bit: Pre-Surgery | Q1: Very much: Pre-Surgery | Q1: Not at all: Adjuvant Cycle 4 | Q1: A little bit: Adjuvant Cycle 4 | Q1: Somewhat: Adjuvant Cycle 4 | Q1: Quite a bit: Adjuvant Cycle 4 | Q1: Very much: Adjuvant Cycle 4 | Q1: Not at all: Adjuvant Cycle 8 | Q1: A little bit: Adjuvant Cycle 8 | Q1: Somewhat: Adjuvant Cycle 8 | Q1: Quite a bit: Adjuvant Cycle 8 | Q1: Very much: Adjuvant Cycle 8 | Q1: Not at all: End of Therapy | Q1: A little bit: End of Therapy | Q1: Somewhat: End of Therapy | Q1: Quite a bit: End of Therapy | Q1: Very much: End of Therapy | Q1: Not at all: Follow-up 2 | Q1: A little bit: Follow-up 2 | Q1: Somewhat: Follow-up 2 | Q1: Quite a bit: Follow-up 2 | Q1: Very much: Follow-up 2 | Q1: Not at all: Follow-up 4 | Q1: A little bit: Follow-up 4 | Q1: Somewhat: Follow-up 4 | Q1: Quite a bit: Follow-up 4 | Q1: Very much: Follow-up 4 | Q2: Not at all: Baseline | Q2: A little bit: Baseline | Q2: Somewhat: Baseline | Q2: Quite a bit: Baseline | Q2: Very much: Baseline | Q2: Not at all: Neoadjuvant Cycle 3 | Q2: A little bit: Neoadjuvant Cycle 3 | Q2: Somewhat: Neoadjuvant Cycle 3 | Q2: Quite a bit: Neoadjuvant Cycle 3 | Q2: Very much: Neoadjuvant Cycle 3 | Q2: Not at all: Neoadjuvant Cycle 5 | Q2: A little bit: Neoadjuvant Cycle 5 | Q2: Somewhat: Neoadjuvant Cycle 5 | Q2: Quite a bit: Neoadjuvant Cycle 5 | Q2: Very much: Neoadjuvant Cycle 5 | Q2: Not at all: Pre-Surgery | Q2: A little bit: Pre-Surgery | Q2: Somewhat: Pre-Surgery | Q2: Quite a bit: Pre-Surgery | Q2: Very much: Pre-Surgery | Q2: Not at all: Adjuvant Cycle 4 | Q2: A little bit: Adjuvant Cycle 4 | Q2: Somewhat: Adjuvant Cycle 4 | Q2: Quite a bit: Adjuvant Cycle 4 | Q2: Very much: Adjuvant Cycle 4 | Q2: Not at all: Adjuvant Cycle 8 | Q2: A little bit: Adjuvant Cycle 8 | Q2: Somewhat: Adjuvant Cycle 8 | Q2: Quite a bit: Adjuvant Cycle 8 | Q2: Very much: Adjuvant Cycle 8 | Q2: Not at all: End of Therapy | Q2: A little bit: End of Therapy | Q2: Somewhat: End of Therapy | Q2: Quite a bit: End of Therapy | Q2: Very much: End of Therapy | Q2: Not at all: Follow-up 2 | Q2: A little bit: Follow-up 2 | Q2: Somewhat: Follow-up 2 | Q2: Quite a bit: Follow-up 2 | Q2: Very much: Follow-up 2 | Q2: Not at all: Follow-up 4 | Q2: A little bit: Follow-up 4 | Q2: Somewhat: Follow-up 4 | Q2: Quite a bit: Follow-up 4 | Q2: Very much: Follow-up 4 |
|---|
| T-DM1 + P | 72.6 | 16.1 | 0 | 2.2 | 0.4 | 48.9 | 27.4 | 0 | 4.0 | 1.8 | 46.2 | 26.0 | 0 | 6.3 | 1.3 | 48.0 | 21.5 | 0 | 5.8 | 1.3 | 39.0 | 21.5 | 0 | 6.7 | 2.2 | 39.0 | 15.7 | 0 | 6.3 | 3.1 | 42.6 | 22.9 | 0 | 6.7 | 1.8 | 39.9 | 14.8 | 0 | 4.0 | 2.2 | 37.7 | 12.1 | 0 | 4.5 | 1.3 | 67.3 | 17.9 | 0 | 5.8 | 0.4 | 24.2 | 38.6 | 0 | 14.8 | 4.5 | 25.6 | 37.7 | 0 | 12.6 | 4.0 | 27.4 | 37.2 | 0 | 8.1 | 4.0 | 24.2 | 30.9 | 0 | 9.4 | 4.9 | 25.6 | 24.2 | 0 | 9.9 | 4.5 | 27.4 | 30.0 | 0 | 13.5 | 3.1 | 27.8 | 25.6 | 0 | 6.3 | 1.3 | 30.0 | 18.8 | 0 | 4.5 | 2.2 |
,| TCH + P | 71.9 | 14.9 | 0 | 2.3 | 0 | 35.3 | 31.2 | 0 | 10.9 | 2.3 | 48.9 | 23.1 | 0 | 7.7 | 2.3 | 40.3 | 26.7 | 0 | 7.2 | 2.7 | 38.5 | 23.5 | 0 | 9.5 | 6.8 | 34.8 | 27.6 | 0 | 9.0 | 4.1 | 39.4 | 26.7 | 0 | 6.8 | 4.5 | 43.9 | 19.0 | 0 | 3.6 | 0.9 | 46.2 | 10.4 | 0 | 3.2 | 1.4 | 64.7 | 21.3 | 0 | 3.2 | 0.5 | 14.0 | 40.7 | 0 | 18.6 | 6.8 | 21.3 | 35.7 | 0 | 20.4 | 5.0 | 21.3 | 33.9 | 0 | 15.4 | 6.3 | 23.5 | 33.0 | 0 | 13.1 | 9.0 | 23.1 | 35.7 | 0 | 12.2 | 5.0 | 27.1 | 33.9 | 0 | 10.0 | 6.8 | 36.2 | 25.8 | 0 | 4.1 | 1.8 | 39.8 | 14.5 | 0 | 4.5 | 2.7 |
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)
| Intervention | Percentage of Participants (Number) |
|---|
| Not at all: Baseline | A little bit: Baseline | Somewhat: Baseline | Quite a bit: Baseline | Very much: Baseline | Not at all: Neoadjuvant Cycle 3 | A little bit: Neoadjuvant Cycle 3 | Somewhat: Neoadjuvant Cycle 3 | Quite a bit: Neoadjuvant Cycle 3 | Very much: Neoadjuvant Cycle 3 | Not at all: Neoadjuvant Cycle 5 | A little bit: Neoadjuvant Cycle 5 | Somewhat: Neoadjuvant Cycle 5 | Quite a bit: Neoadjuvant Cycle 5 | Very much: Neoadjuvant Cycle 5 | Not at all: Pre-Surgery | A little bit: Pre-Surgery | Somewhat: Pre-Surgery | Quite a bit: Pre-Surgery | Very much: Pre-Surgery | Not at all: Adjuvant Cycle 4 | A little bit: Adjuvant Cycle 4 | Somewhat: Adjuvant Cycle 4 | Quite a bit: Adjuvant Cycle 4 | Very much: Adjuvant Cycle 4 | Not at all: Adjuvant Cycle 8 | A little bit: Adjuvant Cycle 8 | Somewhat: Adjuvant Cycle 8 | Quite a bit: Adjuvant Cycle 8 | Very much: Adjuvant Cycle 8 | Not at all: End of Therapy | A little bit: End of Therapy | Somewhat: End of Therapy | Quite a bit: End of Therapy | Very much: End of Therapy | Not at all: Follow-up 2 | A little bit: Follow-up 2 | Somewhat: Follow-up 2 | Quite a bit: Follow-up 2 | Very much: Follow-up 2 | Not at all: Follow-up 4 | A little bit: Follow-up 4 | Somewhat: Follow-up 4 | Quite a bit: Follow-up 4 | Very much: Follow-up 4 |
|---|
| T-DM1 + P | 81.2 | 9.4 | 0 | 0.9 | 0 | 59.6 | 19.3 | 0 | 2.7 | 0.4 | 54.3 | 21.1 | 0 | 2.7 | 1.8 | 52.0 | 17.9 | 0 | 5.4 | 1.3 | 42.6 | 15.2 | 0 | 9.0 | 2.7 | 31.8 | 19.3 | 0 | 9.0 | 4.0 | 31.4 | 23.8 | 0 | 12.1 | 6.7 | 32.7 | 19.3 | 0 | 7.6 | 1.3 | 32.7 | 17.9 | 0 | 3.1 | 1.8 |
,| TCH + P | 78.7 | 9.5 | 0 | 0.9 | 0.5 | 54.3 | 20.8 | 0 | 3.2 | 1.8 | 37.1 | 29.9 | 0 | 8.6 | 6.8 | 22.6 | 29.0 | 0 | 15.4 | 10.0 | 31.2 | 31.7 | 0 | 9.5 | 6.3 | 33.0 | 28.1 | 0 | 10.9 | 4.1 | 31.2 | 30.8 | 0 | 10.9 | 5.0 | 38.0 | 19.9 | 0 | 5.9 | 4.1 | 39.8 | 15.4 | 0 | 4.1 | 2.3 |
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)
| Intervention | Percentage of Participants (Number) |
|---|
| Not at all: Baseline | A little bit: Baseline | Somewhat: Baseline | Quite a bit: Baseline | Very much: Baseline | Not at all: Neoadjuvant Cycle 3 | A little bit: Neoadjuvant Cycle 3 | Somewhat: Neoadjuvant Cycle 3 | Quite a bit: Neoadjuvant Cycle 3 | Very much: Neoadjuvant Cycle 3 | Not at all: Neoadjuvant Cycle 5 | A little bit: Neoadjuvant Cycle 5 | Somewhat: Neoadjuvant Cycle 5 | Quite a bit: Neoadjuvant Cycle 5 | Very much: Neoadjuvant Cycle 5 | Not at all: Pre-Surgery | A little bit: Pre-Surgery | Somewhat: Pre-Surgery | Quite a bit: Pre-Surgery | Very much: Pre-Surgery | Not at all: Adjuvant Cycle 4 | A little bit: Adjuvant Cycle 4 | Somewhat: Adjuvant Cycle 4 | Quite a bit: Adjuvant Cycle 4 | Very much: Adjuvant Cycle 4 | Not at all: Adjuvant Cycle 8 | A little bit: Adjuvant Cycle 8 | Somewhat: Adjuvant Cycle 8 | Quite a bit: Adjuvant Cycle 8 | Very much: Adjuvant Cycle 8 | Not at all: End of Therapy | A little bit: End of Therapy | Somewhat: End of Therapy | Quite a bit: End of Therapy | Very much: End of Therapy | Not at all: Follow-up 2 | A little bit: Follow-up 2 | Somewhat: Follow-up 2 | Quite a bit: Follow-up 2 | Very much: Follow-up 2 | Not at all: Follow-up 4 | A little bit: Follow-up 4 | Somewhat: Follow-up 4 | Quite a bit: Follow-up 4 | Very much: Follow-up 4 |
|---|
| T-DM1 + P | 87.4 | 4.0 | 0 | 0 | 0 | 65.0 | 16.6 | 0 | 0.4 | 0 | 58.7 | 19.3 | 0 | 1.3 | 0.4 | 49.8 | 24.7 | 0 | 2.2 | 0 | 50.2 | 15.7 | 0 | 2.2 | 1.3 | 48.9 | 14.3 | 0 | 0.9 | 0 | 57.8 | 14.8 | 0 | 0 | 1.3 | 48.4 | 11.7 | 0 | 0.4 | 0.4 | 41.3 | 11.2 | 0 | 2.7 | 0.4 |
,| TCH + P | 81.4 | 7.7 | 0 | 0.5 | 0 | 8.6 | 11.3 | 0 | 20.8 | 39.4 | 20.4 | 19.9 | 0 | 15.8 | 26.2 | 30.8 | 13.6 | 0 | 11.3 | 21.3 | 67.9 | 5.0 | 0 | 3.2 | 2.7 | 70.1 | 4.1 | 0 | 0.9 | 0.9 | 69.7 | 5.4 | 0 | 0.9 | 1.8 | 55.7 | 9.0 | 0 | 1.4 | 1.8 | 52.9 | 7.2 | 0 | 0 | 1.4 |
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)
| Intervention | Probability (Number) |
|---|
| TCH + P | 94.21 |
| T-DM1 + P | 85.28 |
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)
| Intervention | Probability (Number) |
|---|
| TCH + P | 97.6 |
| T-DM1 + P | 97.0 |
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)
| Intervention | Percentage of Participants (Number) |
|---|
| TCH + P | 52.6 |
| T-DM1 + P | 41.7 |
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
| Intervention | Percentage of Participants (Number) |
|---|
| TCH + P | 69.9 |
| T-DM1 + P | 45.4 |
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
| Intervention | months (Median) |
|---|
| Physical Function | Role Function | Cognitive Function |
|---|
| T-DM1 + P | 4.86 | 4.44 | 4.44 |
,| TCH + P | 2.79 | 2.79 | 3.42 |
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
| Intervention | ng/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 + P | 8.18 | NA | 8.22 | NA | 7.98 | NA | 7.90 | NA |
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
| Intervention | nanograms 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 + P | 4.64 | 4.73 | 4.49 | 5.15 |
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)
| Intervention | Percentage of Participants (Number) |
|---|
| Hepatotoxicity | Pulmonary Toxicity | Cardiac Dysfunction | Neutropenia | Thrombocytopenia | Peripheral Neuropathy | Hemorrhage | IRR/Hypersensitivity | IRR/Hypersensitivity symptoms | Rash | Diarrhea | Mucositis |
|---|
| T-DM1 + P | 39.0 | 4.9 | 1.3 | 8.1 | 17.9 | 28.7 | 33.2 | 22.9 | 19.3 | 36.8 | 38.6 | 24.7 |
,| TCH + P | 14.2 | 0.9 | 4.6 | 39.7 | 22.8 | 47.5 | 19.2 | 13.7 | 7.8 | 44.7 | 76.7 | 43.8 |
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
| Intervention | Percentage of participants (Number) |
|---|
| Neoadjuvant Phase (baseline) | Neoadjuvant Phase (post-baseline) | Adjuvant Phase (baseline) | Adjuvant Phase (post-baseline) |
|---|
| T-DM1 + P | 11 | 2.6 | 5.4 | 5.0 |
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
| Intervention | Percentage of Participants (Number) |
|---|
| Neoadjuvant Phase (Baseline) | Neoadjuvant Phase (Post-Baseline) | Adjuvant Phase (Baseline) | Adjuvant Phase (Post-baseline) |
|---|
| T-DM1 + P | 5.5 | 7.5 | 11.7 | 13.1 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Invasive Disease-Free Survival (iDFS) at 1 to 4 Years, Determined by the Investigator According to RECIST v1.1
The Kaplan-Meier method was used to estimate the percentage of participants who were event-free at landmark timepoints. Invasive disease-free survival (iDFS) was defined as the time from the first date of no disease (the date of surgery) to the first documentation of progressive invasive disease, relapse, or death, with tumor evaluations performed by the investigator according to RECIST v1.1. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as progressive disease or relapse. Participants who withdrew from the study without documented progression or relapse and for whom there existed evidence that evaluations had been made, were censored at the date of the last assessment at which the participant was known to be alive and disease-free. Participants with no postbaseline information and participants who did not undergo surgery were excluded from the analysis. (NCT02132949)
Timeframe: At 1, 2, 3, and 4 years
| Intervention | Estimate of percentage of participants (Number) |
|---|
| 1 Year | 2 Years | 3 Years | 4 Years |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 98.91 | 95.57 | 94.42 | 92.60 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 96.34 | 94.25 | 91.06 | 91.06 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1 to 5 Years
The Kaplan-Meier method was used to estimate the percentage of participants who were event-free at landmark timepoints. Overall survival (OS) was defined as the time from enrollment to death from any cause. Participants who were alive or lost to follow-up were censored at their last known date in the study. Participants with no post-baseline assessments were censored at the date of enrollment plus 1 day. (NCT02132949)
Timeframe: At 1, 2, 3, 4, and 5 years
| Intervention | Estimate of percentage of participants (Number) |
|---|
| 1 Year | 2 Years | 3 Years | 4 Years | 5 Years |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 99.48 | 98.96 | 97.86 | 97.86 | 96.10 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 100.00 | 97.94 | 96.38 | 94.81 | 93.75 |
Overview of the Number of Participants With at Least One Adverse Event During the Adjuvant Period
"An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms severe and serious are not synonymous with respect to an AE. Severity refers to the intensity of an AE (rated according to NCI-CTCAE v4.0 criteria or, if not listed, the following scale: Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to AE), whereas a serious AE (SAE) is a significant medical event (per standard criteria). Severity and seriousness needed to be independently assessed for each AE that was recorded. Selected AEs for reporting included heart failure (NYHA Class II/III/IV) and asymptomatic declines in LVEF (reported as an AE with the term of ejection fraction decreased). In the results table, multiple occurrences of the same AE in one individual were counted only once. Any AE includes all serious and non-serious AEs." (NCT02132949)
Timeframe: From the first dose of any study drug after surgery through 42 days after the last dose of any study drug (during the adjuvant treatment period; up to approximately 39 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Any Adverse Event (AE) | NCI-CTCAE Grade 3-5 AE | Serious AE | Deaths | Ejection Fraction Decreased (Any Grade) | Heart Failure (Any Grade) |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 171 | 23 | 15 | 0 | 15 | 0 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 171 | 40 | 17 | 0 | 20 | 2 |
Overview of the Number of Participants With at Least One Adverse Event During the Neoadjuvant Period
"An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms severe and serious are not synonymous with respect to an AE. Severity refers to the intensity of an AE (rated according to NCI-CTCAE v4.0 criteria or, if not listed, the following scale: Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to AE), whereas a serious AE (SAE) is a significant medical event (per standard criteria). Severity and seriousness needed to be independently assessed for each AE that was recorded. Selected AEs for reporting included heart failure (NYHA Class II/III/IV) and asymptomatic declines in LVEF (reported as an AE with the term of ejection fraction decreased). In the results table, multiple occurrences of the same AE in one individual were counted only once. Any AE includes all serious and non-serious AEs." (NCT02132949)
Timeframe: From first dose of any study drug prior to surgery through the day before the first dose of study drug after surgery (up to 25 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Any Adverse Event (AE) | NCI-CTCAE Grade 3-5 AE | Serious AE | Deaths | Ejection Fraction Decreased (Any Grade) | Heart Failure (Any Grade) |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 198 | 99 | 45 | 0 | 14 | 4 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 198 | 108 | 52 | 0 | 7 | 0 |
Overview of the Number of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period
"An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. The terms severe and serious are not synonymous. Severity refers to the intensity of an AE (rated according to NCI-CTCAE v4.0 criteria or, if not listed, the following scale: Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to AE), and a serious AE (SAE) is a significant medical event (per standard criteria). Severity and seriousness were independently assessed for each AE. Selected AEs for reporting included heart failure (NYHA Class II/III/IV) and asymptomatic declines in LVEF (reported as ejection fraction decreased). During TFFU, only heart failure, pregnancies, and non-breast-related second primary malignancies, irrespective of causal relationship with study treatment, and drug-related SAEs were reported. Multiple occurrences of the same AE in 1 subject were counted only once." (NCT02132949)
Timeframe: From 42 days after the last dose of study treatment until the end of treatment-free follow-up (TFFU; up to 5 years)
| Intervention | Participants (Count of Participants) |
|---|
| Any Adverse Event (AE) | NCI-CTCAE Grade 3-5 AE | Serious AE | Deaths | Ejection Fraction Decreased (Any Grade) | Heart Failure (Any Grade) |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 3 | 2 | 3 | 7 | 1 | 0 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 7 | 5 | 7 | 13 | 1 | 1 |
Percentage of Participants Positive for Anti-Therapeutic Antibodies (ATAs) to Pertuzumab at Baseline and Anytime Post-Baseline
ATAs to pertuzumab in serum samples were detected using a validated bridging enzyme-linked immunosorbent assay (ELISA) method. This analysis only included participants with an ATA assay result from a baseline sample and/or at least one post-baseline sample. (NCT02132949)
Timeframe: Screening (baseline) then prior to pertuzumab infusion (Hour 0) in Cycles 5, 14, 18 thereafter anytime between Cycle 8 Day 21 and surgery, up to treatment completion visit (cycle length=2-3 weeks; up to approximately 1 year, 3 months)
| Intervention | Percentage of participants (Number) |
|---|
| At Baseline | Anytime Post-Baseline |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 1.6 | 4.6 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 2.1 | 3.6 |
Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Adjuvant Treatment Period
LVEF significant decline was defined as the decline in LVEF of >/= 10%-points from baseline to an LVEF of < 50%. A Confirmed LVEF Significant Decline was defined as at least two consecutive readings of significant declines in LVEF. A Single LVEF Significant Decline was defined as only one reading of a significant decline (no consecutive readings) in LVEF. The category of 'At Least one LVEF Significant Decline Event' was defined as the total of confirmed and single LVEF significant declines. The 95% confidence intervals were calculated using the Clopper-Pearson method. Results included events with onset from the first dose of any study drug after surgery through 42 days after the last dose of any study drug. (NCT02132949)
Timeframe: From the first dose of any study drug after surgery through 42 days after the last dose of any study drug (during the adjuvant treatment period; up to approximately 39 weeks)
| Intervention | percentage of participants (Number) |
|---|
| At Least One LVEF Significant Decline Event (Confirmed+Single) | At Least One Confirmed LVEF Significant Decline | At Least One Single LVEF Significant Decline |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 7.7 | 2.8 | 5.0 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 10.5 | 3.2 | 7.4 |
Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Neoadjuvant Treatment Period
LVEF significant decline was defined as the decline in LVEF of >/= 10%-points from baseline to an LVEF of < 50%. A Confirmed LVEF Significant Decline was defined as at least two consecutive readings of significant declines in LVEF. A Single LVEF Significant Decline was defined as only one reading of a significant decline (no consecutive readings) in LVEF. The category of 'At Least one LVEF Significant Decline Event' was defined as the total of confirmed and single LVEF significant declines. The 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method. Results include events with onset from the first dose of pertuzumab or trastuzumab prior to surgery through the day before the first dose of any study drug after surgery. If participant withdrew without entering adjuvant period, results included all events with onset from first dose of pertuzumab or trastuzumab through 42 days after last dose of any study drug or on the day of target surgery whichever is later. (NCT02132949)
Timeframe: From day of first dose of pertuzumab or trastuzumab until the end of the neoadjuvant treatment period (as defined in the description; up to 25 weeks)
| Intervention | percentage of participants (Number) |
|---|
| At Least One LVEF Significant Decline Event (Confirmed+Single) | At Least One Confirmed LVEF Significant Decline | At Least One Single LVEF Significant Decline |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 6.5 | 1.0 | 5.5 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 2.0 | 0.5 | 1.5 |
Percentage of Participants With at Least One Left Ventricular Ejection Fraction (LVEF) Significant Decline, Defined as a Drop in LVEF of at Least 10 Percentage Points From Baseline and to Below 50%, During the Treatment-Free Follow-Up Period
LVEF significant decline was defined as the decline in LVEF of >/= 10%-points from baseline to an LVEF of < 50%. A Confirmed LVEF Significant Decline was defined as at least two consecutive readings of significant declines in LVEF. A Single LVEF Significant Decline was defined as only one reading of a significant decline (no consecutive readings) in LVEF. The category of 'At Least one LVEF Significant Decline Event' was defined as the total of confirmed and single LVEF significant declines. The 95% confidence intervals were calculated using the Clopper-Pearson method. (NCT02132949)
Timeframe: From 42 days after the last dose of study treatment until the end of treatment-free follow-up (up to 5 years)
| Intervention | Percentage of participants (Number) |
|---|
| At Least One LVEF Significant Decline Event (Confirmed+Single) | At Least One Confirmed LVEF Significant Decline | At Least One Single LVEF Significant Decline |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 6.0 | 3.0 | 3.0 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 3.5 | 1.0 | 2.5 |
Percentage of Participants With Clinical Response as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 During the Neoadjuvant Treatment Period
The clinical response rate was defined as the percentage of participants in the ITT population who achieved a complete response (CR) or partial response (PR) prior to surgery, according to RECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of the longest diameter compared to Baseline. Stable Disease (SD): neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. Progressive Disease (PD): at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. Participants were classified as missing or unevaluable if no assessments were measured prior to surgery on the ipsilateral breast. The 95% CIs were calculated using the Clopper-Pearson method; they were only calculated for responses (not for missing or unevaluable data). (NCT02132949)
Timeframe: From Baseline until disease progression or death due to any cause up to 24 weeks (during the neoadjuvant treatment period; assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks])
| Intervention | Percentage of participants (Number) |
|---|
| Clinical Response Rate (CR+PR) | Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Missing or Unevaluable |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 67.3 | 39.7 | 27.6 | 7.0 | 0.5 | 25.1 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 60.2 | 23.9 | 36.3 | 10.0 | 1.0 | 28.9 |
Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Treatment-Free Follow-Up Period
Symptomatic left ventricular systolic dysfunction (otherwise referred to as heart failure) is a serious adverse event. The NYHA Functional Classification System for Heart Failure considers the patient's symptoms: Class III: Marked limitation of physical activity; Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort; Symptoms of heart failure at rest; If any physical activity is undertaken, discomfort increases. The 95% CIs were calculated with the Clopper-Pearson method. (NCT02132949)
Timeframe: From 42 days after the last dose of study treatment until the end of treatment-free follow-up (up to 5 years)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 0 |
| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 0.5 |
Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Adjuvant Treatment Period
Symptomatic left ventricular systolic dysfunction (otherwise referred to as heart failure) is a serious adverse event. The NYHA Functional Classification System for Heart Failure considers the patient's symptoms: Class III: Marked limitation of physical activity; Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort; Symptoms of heart failure at rest; If any physical activity is undertaken, discomfort increases. The 95% CIs were calculated with the Clopper-Pearson method. Results included events with onset from the first dose of any study drug after surgery through 42 days after the last dose of any study drug. (NCT02132949)
Timeframe: From the first dose of any study drug after surgery through 42 days after the last dose of any study drug (during the adjuvant treatment period; up to approximately 39 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 0 |
| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 0.5 |
Percentage of Participants With at Least One Event of New York Heart Association (NYHA) Class III or IV Heart Failure During the Neoadjuvant Treatment Period
Symptomatic left ventricular systolic dysfunction (otherwise referred to as heart failure) is a serious adverse event. The NYHA Functional Classification System for Heart Failure considers the patient's symptoms: Class III: Marked limitation of physical activity; Comfortable at rest, but less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort; Symptoms of heart failure at rest; If any physical activity is undertaken, discomfort increases. The 95% CIs were calculated with the Clopper-Pearson method. Results included events with onset from first dose of pertuzumab/trastuzumab prior to surgery through the day before the first dose of any study drug after surgery. If participant withdrew without entering adjuvant period, results included all events with onset from first dose of pertuzumab/trastuzumab through 42 days after last dose of any study drug or on the day of target surgery whichever was later. (NCT02132949)
Timeframe: From day of first dose of pertuzumab or trastuzumab until the end of the neoadjuvant treatment period (as defined in the description; up to 25 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 1.5 |
| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 0 |
Percentage of Participants With Total Pathologic Complete Response (tpCR), Evaluated After Surgery
Total pathologic complete response (tpCR) was the pCR based on tumor and nodal staging (i.e., histological confirmation of pCR in breast and nodes at surgery) and was defined as the absence of any residual invasive cancer in the breast and the absence of any metastatic cells in the regional lymph nodes (i.e., ypT0/is ypN0 tpCR). Participants who did not undergo surgery or did not have a valid pCR assessment were considered non-responders in the analysis. The 95% CIs were calculated using the Clopper-Pearson method. (NCT02132949)
Timeframe: After completion of neoadjuvant treatment and surgery (up to 25 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 61.8 |
| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 60.7 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1 to 5 Years, Determined by the Investigator According to RECIST v1.1
The Kaplan-Meier method was used to estimate the percentage of participants who were event-free at landmark timepoints. Event-free survival (EFS) was defined as the time from enrollment to the first occurrence of progressive disease (PD), relapse, or death from any cause, with tumor evaluations performed by the investigator according to RECIST v1.1. Ipsilateral or contralateral in situ disease and second primary non-breast cancers (including in situ carcinomas and non-melanoma skin cancers) were not counted as progressive disease or relapse. Participants who withdrew from the study without documented progression or relapse and for whom there existed evidence that evaluations had been made, were censored at the date of the last assessment at which the participant was known to be free from progressive disease or relapse. Participants with no tumor evaluations after baseline were censored at the date of enrollment plus 1 day. (NCT02132949)
Timeframe: At 1, 2, 3, 4, and 5 years
| Intervention | Estimate of percentage of participants (Number) |
|---|
| 1 Year | 2 Years | 3 Years | 4 Years | 5 Years |
|---|
| Cohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab | 98.47 | 95.80 | 93.58 | 92.39 | 90.84 |
,| Cohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab | 97.48 | 92.86 | 90.78 | 89.73 | 89.20 |
Progression-Free Survival (PFS)
PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions. (NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | months (Median) |
|---|
| Arm A: Trastuzumab Emtansine | 10.3 |
| Arm B: Trastuzumab + Docetaxel | 8.2 |
Patient-Reported Outcomes: Number of Participants Who Completed the FACT-Taxane Questionnaire
The FACT - Taxane is a self-reported instrument which measures the HRQOL of participants receiving taxane containing chemotherapy. The FACT-Taxane consists of 16 items and was designed to assess the impact of taxane treatment-related symptoms from the participant's perspective. (NCT02144012)
Timeframe: Days 1 and 8 of Cycles 1 and 2 and on the first day of each subsequent 21-day cycle thereafter as well as at study drug completion or discontinuation visit (up to 20 months)
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 1 Day 1 | Cycle 1 Day 8 | Cycle 2 Day 1 | Cycle 2 Day 8 | Cycle 3 Day 1 | Cycle 4 Day 1 | Cycle 5 Day 1 | Cycle 6 Day 1 | Cycle 7 Day 1 | Cycle 8 Day 1 | Cycle 9 Day 1 | Cycle 10 Day 1 | Cycle 11 Day 1 | Cycle 12 Day 1 | Cycle 13 Day 1 | Cycle 14 Day 1 | Cycle 15 Day 1 | Cycle 16 Day 1 | Cycle 17 Day 1 | Cycle 18 Day 1 | Cycle 19 Day 1 | Cycle 20 Day 1 | Study Drug Completion/Discontinuation Visit |
|---|
| Arm A: Trastuzumab Emtansine | 27 | 27 | 29 | 29 | 33 | 30 | 27 | 23 | 18 | 16 | 15 | 12 | 11 | 9 | 8 | 7 | 6 | 3 | 2 | 2 | 1 | 0 | 33 |
,| Arm B: Trastuzumab + Docetaxel | 14 | 15 | 15 | 15 | 15 | 14 | 13 | 12 | 11 | 11 | 10 | 7 | 7 | 7 | 5 | 5 | 4 | 4 | 2 | 1 | 1 | 1 | 13 |
Safety: Percentage of Participants With Significant Decline in Left Ventricular Ejection Fraction (LVEF)
Significant decline in LVEF was defined as LVEF below 50% and decrease from baseline of 15% points or more. Echocardiogram or multiple-gated acquisition (MUGA) scan was used to assess LVEF. (NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 0 |
| Arm B: Trastuzumab + Docetaxel | 0 |
Safety: Percentage of Participants With Grade 3 and 4 AEs
Grade 3 and 4 AEs were evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Grade 3 was defined as severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care activities of daily living, including bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. Grade 4 was defined as life-threatening consequences; urgent intervention indicated. (NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 20.6 |
| Arm B: Trastuzumab + Docetaxel | 66.7 |
Safety: Percentage of Participants With Adverse Events Leading to Treatment Interruption
(NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 11.8 |
| Arm B: Trastuzumab + Docetaxel | 33.3 |
Patient-Reported Outcomes: Number of Participants Who Completed the Functional Assessment of Cancer Therapy-Breast Cancer (FACT-B) Questionnaire
The FACT-B (version 4) is a self-reported instrument which measures health-related quality of life (HRQOL) of participants with breast cancer.The FACT-B includes the breast cancer sub-scale (BCS) and is comprised of nine items specific to assessing patients' HRQOL in breast cancer. (NCT02144012)
Timeframe: On the first Day of each 21-day Cycle (Day 1, 22, 43, etc.) and at study drug completion or discontinuation visit (up to 20 months)
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 | Cycle 3 Day 1 | Cycle 4 Day 1 | Cycle 5 Day 1 | Cycle 6 Day 1 | Cycle 7 Day 1 | Cycle 8 Day 1 | Cycle 9 Day 1 | Cycle 10 Day 1 | Cycle 11 Day 1 | Cycle 12 Day 1 | Cycle 13 Day 1 | Cycle 14 Day 1 | Cycle 15 Day 1 | Cycle 16 Day 1 | Cycle 17 Day 1 | Cycle 18 Day 1 | Cycle 19 Day 1 | Cycle 20 Day 1 | Study Drug Completion/Discontinuation Visit |
|---|
| Arm A: Trastuzumab Emtansine | 34 | 34 | 33 | 30 | 27 | 23 | 18 | 16 | 15 | 12 | 11 | 9 | 8 | 7 | 6 | 3 | 2 | 2 | 1 | 0 | 33 |
,| Arm B: Trastuzumab + Docetaxel | 15 | 15 | 15 | 14 | 13 | 12 | 11 | 11 | 10 | 7 | 7 | 7 | 5 | 5 | 4 | 4 | 2 | 1 | 1 | 1 | 13 |
Safety: Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 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. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 94.1 |
| Arm B: Trastuzumab + Docetaxel | 100 |
Safety: Percentage of Participants With Adverse Events Leading to Dose Reduction
(NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 2.9 |
| Arm B: Trastuzumab + Docetaxel | 26.7 |
One-Year Survival Rate
One-year survival rate as determined by Kaplan-Meier estimates. (NCT02144012)
Timeframe: At 12 months
| Intervention | percentage of participants (Median) |
|---|
| Arm A: Trastuzumab Emtansine | 92.31 |
| Arm B: Trastuzumab + Docetaxel | 100.00 |
Objective Response Rate (ORR)
ORR was defined as percentage of participants with partial response (PR) or complete response (CR) determined on the basis of investigator assessments with the use of RECIST v1.1. Tumor assessments were performed with computed tomography (CT) or magnetic resonance imaging (MRI) scans of the chest, abdomen, and pelvis. CR: disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions; Objective Response Rate (OR) = CR + PR. (NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 48.1 |
| Arm B: Trastuzumab + Docetaxel | 71.4 |
Immunogenicity: Percentage of Positive Anti-Therapeutic Antibody (ATA) Response to Trastuzumab Emtansine
(NCT02144012)
Timeframe: Day 1, Cycle 1 (Day 1), Day 1, Cycle 4 (Day 64) and at study drug completion or discontinuation visit (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 3.0 |
Percentage of Participants With Adverse Events Leading to Treatment Discontinuation
(NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Trastuzumab Emtansine | 14.7 |
| Arm B: Trastuzumab + Docetaxel | 20.0 |
Duration of Response (DOR)
DOR was defined as the time from the date of initial confirmed PR or CR to the date of disease progression or death within the study. CR: disappearance of all target lesions; PR: >=30% decrease in the sum of the longest diameter of target lesions. Disease progression was defined according to RECIST, v1.1 as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 mm or the appearance of one or more new lesions. (NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | months (Median) |
|---|
| Arm A: Trastuzumab Emtansine | NA |
| Arm B: Trastuzumab + Docetaxel | 6.2 |
Overall Survival (OS)
OS was defined as the time from the date of randomization to the date of death from any cause. (NCT02144012)
Timeframe: At time of clinical data cut-off (up to 20 months)
| Intervention | months (Median) |
|---|
| Arm A: Trastuzumab Emtansine | NA |
| Arm B: Trastuzumab + Docetaxel | NA |
Overall Survival (OS)
Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the OS will be calculated. (NCT02145078)
Timeframe: From the date of protocol-specified treatment initiation to the date of death or last observation, assessed up to 12 months
| Intervention | months (Median) |
|---|
| Treatment (Chemotherapy Regimen) | 2.0 |
Progression-free Survival (PFS)
Each biomarker evaluated using its expression level (continuous variable) and dichotomous form (based on a median cutoff). A univariable Cox regression model will be used to assess the relationship of expression levels of each biomarker to PFS. In addition, for the dichotomous variables, the sample will be divided into those above and below the median for each biomarker. PFS probabilities for each group will be estimated using the Kaplan-Meier method, with standard errors based on Greenwood's formula. Log rank tests will be used to determine the level of significance between survival curves. Since, the study was canceled due to slow accrual, no biomarkers were measured; therefore, no analysis with biomarkers. Only the PFS will be calculated. (NCT02145078)
Timeframe: From the date of protocol-specified treatment initiation to the date of progression, death, or last observation, assessed up to 12 months
| Intervention | days (Median) |
|---|
| Treatment (Chemotherapy Regimen) | 42 |
Screen Success Rate
"Percentage of participants that registered to a therapeutic sub-study out of those who received a sub-study assignment.~To receive a sub-study assignment, enrolled participants must have submitted tissue, had biomarker results, and been matched to a therapeutic sub-study." (NCT02154490)
Timeframe: From date of registration to pre-screening or screening component until sub-study registration or death, a median of 3.5 months (IQR 2.0-6.0) in the pre-screened group and 0.9 months (IQR 0.7-1.1) in the screened at progression group.
| Intervention | Participants (Count of Participants) |
|---|
| Assigned Participants | 655 |
Objective Response Rate (ORR)
To further assess the efficacy of various sequences. Objective response rate (ORR; per RECIST 1.1 as assessed by the site Investigator) is defined as the number (%) of patients with a confirmed overall response of CR or PR and was based on the evaluable analysis set. Per 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. (NCT02179671)
Timeframe: Up to 2 years
| Intervention | patients (%) (Number) |
|---|
| Tremelimumab (1 Cycle) With a Seq. Switch to a MEDI4736 | 11.1 |
| Tremelimumab (2 Cycles) With a Seq. Switch to MEDI4736 | 0 |
Overall Survival
To assess the efficacy of various sequences. In survival follow up at data cut off. (NCT02179671)
Timeframe: Up to 2 years
| Intervention | patients (Number) |
|---|
| Tremelimumab (1 Cycle) With a Seq. Switch to a MEDI4736 | 0 |
| Tremelimumab (2 Cycles) With a Seq. Switch to MEDI4736 | 0 |
Progression-free Survival
Progression-free survival (per RECIST 1.1 as assessed by Investigator) is defined as the date of 1st dose of MEDI4736 until the date of objective disease progression or death. Progression of disease (PD) At least a 20% increase in the sum of diameters of TLs, 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. (NCT02179671)
Timeframe: Up to 2 years
| Intervention | patients (Number) |
|---|
| Tremelimumab (1 Cycle) With a Seq. Switch to a MEDI4736 | 1 |
| Tremelimumab (2 Cycles) With a Seq. Switch to MEDI4736 | 0 |
Confirmed Complete Response (CR) Rate
To assess the efficacy of various sequences. CR (per RECIST 1.1 as assessed by the local/site Investigator) is defined as the disappearance of all target and non-target lesions. Confirmed complete response rate (CR rate) is defined as the number (%) of patients with a confirmed overall response of CR and was based on the evaluable analysis set. (NCT02179671)
Timeframe: Up to 2 years
| Intervention | patients (%) (Number) |
|---|
| Tremelimumab (1 Cycle) With a Seq. Switch to a MEDI4736 | 0 |
| Tremelimumab (2 Cycles) With a Seq. Switch to MEDI4736 | 0 |
Duration of Response
Duration of response (DoR; per RECIST 1.1 as assessed by the site Investigator) will be defined as the time from the date of 1st documented response (which is subsequently confirmed) until the 1st date of documented progression or death in the absence of disease progression. (NCT02179671)
Timeframe: Within 12 months
| Intervention | Months (Median) |
|---|
| Tremelimumab (1 Cycle) With a Seq. Switch to a MEDI4736 | NA |
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
| Intervention | Percentage of participants (Number) |
|---|
| PF-05280014 | 92.1 |
| Trastuzumab-EU | 93.3 |
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
| Intervention | μg/mL (Mean) |
|---|
| Cycle 1/Day 1 0 hours N= 101, 88 | Cycle 1/Day 1 1 hour N= 97, 80 | Cycle 2/Day 21 0 hours N= 99, 88 | Cycle 4/Day 63 0 hours N= 98, 89 | Cycle 5/Day 84 0 hours N= 101, 87 | Cycle 5/Day 84 1 hour N= 90, 80 | Cycle 6/Day 105 0 hours N= 101, 89 |
|---|
| PF-05280014 | 2.313 | 160.4 | 24.29 | 33.43 | 35.01 | 137.0 | 37.77 |
,| Trastuzumab-EU | 1.318 | 164.8 | 27.20 | 37.33 | 40.44 | 138.8 | 40.10 |
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
| Intervention | Percentage of participants (Number) |
|---|
| PF-05280014 | 88.1 |
| Trastuzumab-EU | 82.0 |
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
| Intervention | Percentage of participants (Number) |
|---|
| PF-05280014 | 47.0 |
| Trastuzumab-EU | 50.0 |
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
| Intervention | Number of participants (Number) |
|---|
| Cycle 1 (n=113,112) | Cycle 2 (n=110,112) | Cycle 4 (n=108,110) | Cycle 6 (n=108,108) |
|---|
| PF-05280014 | 0 | 0 | 0 | 0 |
,| Trastuzumab-EU | 0 | 0 | 0 | 0 |
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
| Intervention | Number of participants (Number) |
|---|
| Cycle 1 (n=113,112) | Cycle 2 (n=111,112) | Cycle 4 (n=108,109) | Cycle 6 (n=108,108) |
|---|
| PF-05280014 | 0 | 0 | 0 | 0 |
,| Trastuzumab-EU | 1 | 0 | 0 | 0 |
Disease Control According to Response Evaluation Criteria in Solid Tumours (RECIST), Version 1.1
This outcome measure presents the number of patients with disease control according to RECIST, version 1.1, defined as number of patients with Complete response, partial response or stable disease. (NCT02231164)
Timeframe: Up to 6 months.
| Intervention | Percentage of participants (Number) |
|---|
| Yes | No |
|---|
| Nintedanib | 50.0 | 50.0 |
,| Placebo | 66.7 | 33.3 |
Number of Participants Who Experienced At Least One AE in Participants With PD-L1 ≥1% CPS
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 can 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 is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who experienced at least one AE is presented. (NCT02252042)
Timeframe: Up to approximately 33 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 193 |
| Standard Treatment | 178 |
Number of Participants Who Discontinued Study Treatment Due to an AE in All Participants
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 can 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 is temporally associated with the use of study treatment, is also an AE. The number of all participants who discontinued study treatment due to an AE is presented. (NCT02252042)
Timeframe: Up to approximately 30 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 30 |
| Standard Treatment | 36 |
Updated Final OS for 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 to be censored at the date of the last follow-up. The updated OS for all participants is presented. These OS results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 8.4 |
| Standard Treatment | 6.9 |
Time to Progression (TTP) Per RECIST 1.1 in All Participants
TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.2 |
| Standard Treatment | 2.2 |
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 for All Participants
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.1 |
| Standard Treatment | 2.3 |
PFS Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded central imaging vendor review 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The PFS per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.2 |
| Standard Treatment | 2.3 |
PFS Per Modified RECIST in All Participants
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review 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. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 3.5 |
| Standard Treatment | 4.8 |
PFS Per Modified RECIST 1.1 in Participants With PD-L1 ≥1% CPS
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on blinded central imaging vendor review 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. Note: The appearance of one or more new lesions was also considered PD. Modified RECIST is similar to RECIST 1.1 with the exception that a confirmation assessment of PD (>4 weeks after the initial PD) is required for participants who remain on treatment following a documented PD per RECIST 1.1. The PFS per modified RECIST for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 3.6 |
| Standard Treatment | 4.8 |
OS for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Expression Defined by ≥1% Combined Positive Score (CPS)(PD-L1 ≥1% CPS)
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. The OS for all participants with PD-L1 expression ≥1% CPS was presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 8.7 |
| Standard Treatment | 7.1 |
Duration of Response (DOR) Per RECIST 1.1 in All Participants
For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 18.4 |
| Standard Treatment | 5.0 |
TTP Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
TTP was defined as the time from randomization to the first documented disease progression based on assessments by the blinded central imaging vendor review per RECIST 1.1. 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. The TTP per RECIST 1.1 for all participants with PD-L1 ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.7 |
| Standard Treatment | 2.3 |
Initial Overall Survival (OS) for 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 to be censored at the date of the last follow-up. The OS for all participants is presented. These initial OS results are based on a data cutoff date of 15-May-2017 with a database lock date of 04-Jun-2017. At the time of the database lock of 04-Jun-2017, there was incomplete collection of survival data for 12 participants. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 8.4 |
| Standard Treatment | 7.1 |
DOR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
For participants who demonstrated a confirmed CR or PR per RECIST 1.1, DOR was defined as the time from first documented evidence of a confirmed CR or PR per RECIST 1.1 until disease progression per RECIST 1.1 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 have demonstrated an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered progression. DOR assessments were based on blinded central imaging vendor review with confirmation. The DOR per RECIST 1.1 for all participants with PD-L1 ≥1% CPS who experienced a confirmed CR or PR is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 18.4 |
| Standard Treatment | 9.6 |
Number of Participants Who Experienced At Least One Adverse Event (AE) in All Participants
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 can 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 is temporally associated with the use of study treatment, is also an AE. The number of all participants who experienced at least one AE is presented. (NCT02252042)
Timeframe: Up to approximately 33 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 240 |
| Standard Treatment | 227 |
ORR Per RECIST 1.1 in Participants With PD-L1 ≥1% CPS
ORR was defined as the percentage of the 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 RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants with PD-L1 expression ≥1% CPS is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 17.3 |
| Standard Treatment | 9.9 |
Objective Response Rate (ORR) Per RECIST 1.1 in All Participants
ORR was defined as the percentage of the 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 RECIST 1.1 based on blinded central imaging vendor review with or without confirmation. The ORR per RECIST 1.1 for all participants is presented. These efficacy results were reported after complete acquisition of all outstanding survival data using a 15-May-2017 data cut-off date with a database update date of 13-Oct-2017. (NCT02252042)
Timeframe: Up to approximately 2 years
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 14.6 |
| Standard Treatment | 10.1 |
Number of Participants Who Discontinued Study Treatment Due to an AE in Participants With PD-L1 ≥1% CPS
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 can 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 is temporally associated with the use of study treatment, is also an AE. The number of all participants with PD-L1 ≥1% CPS who discontinued study treatment due to an AE is presented. (NCT02252042)
Timeframe: Up to approximately 30 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 25 |
| Standard Treatment | 29 |
Number of Participants Who Discontinued Study Treatment 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. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who discontinued study treatment due to an AE was reported for each arm. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Participants (Number) |
|---|
| Control | 36 |
| Pembrolizumab | 28 |
Number of Participants Who Experienced 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. Participants were monitored for the occurrence nonserious AEs for up to 30 days after last dose of study treatment and for serious AEs for up to 90 days after last dose of study treatment. The number of participants who experienced an AE was reported for each arm. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Participants (Number) |
|---|
| Control | 250 |
| Pembrolizumab | 250 |
Objective Response Rate (ORR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
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 RECIST 1.1. ORR was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Control | 6.7 |
| Pembrolizumab | 20.3 |
ORR Per mRECIST - All Participants
ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Control | 11.4 |
| Pembrolizumab | 25.2 |
ORR Per mRECIST - Participants With PD-L1 Positive Tumors
ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Control | 9.2 |
| Pembrolizumab | 28.2 |
ORR Per mRECIST - Participants With Strongly PD-L1 Positive Tumors
ORR per mRECIST was defined as the percentage of participants in the analysis population who had a CR (complete disappearance of all lesions (and no new lesions), with confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented) or a PR (decrease in tumor burden ≥50% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation). ORR per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Control | 7.8 |
| Pembrolizumab | 24.3 |
ORR Per RECIST 1.1 - All Participants
ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in all participants up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Control | 11.0 |
| Pembrolizumab | 21.1 |
ORR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors
ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Control | 8.3 |
| Pembrolizumab | 22.7 |
OS - Participants With PD-L1 Positive Tumors
OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with PD-L1 CPS ≥1% were considered to have a PD-L1 positive tumor status. OS was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016. (NCT02256436)
Timeframe: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
| Intervention | Months (Median) |
|---|
| Control | 6.9 |
| Pembrolizumab | 11.3 |
OS - Participants With Strongly PD-L1 Positive Tumors
OS was defined as the time from randomization to death due to any cause. For the purposes of this study, participants with a PD-L1 CPS ≥10% were considered to have a strongly PD-L1 positive tumor status. The OS was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016. (NCT02256436)
Timeframe: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
| Intervention | Months (Median) |
|---|
| Control | 5.2 |
| Pembrolizumab | 8.0 |
PFS Per Modified RECIST (mRECIST) - Participants With Strongly PD-L1 Positive Tumors
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 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. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with strongly PD-L1 positive tumors (CPS ≥10%) up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Control | 3.3 |
| Pembrolizumab | 2.1 |
PFS Per mRECIST - All Participants
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined as at least 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. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in all randomized participants up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Control | 3.4 |
| Pembrolizumab | 2.2 |
PFS Per mRECIST - Participants With PD-L1 Positive Tumors
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per mRECIST, PD was defined was defined as at least 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. Note: The appearance of one or more new lesions was also considered PD. Per mRECIST, confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required for participants remaining on treatment following PD per RECIST 1.1. PFS per mRECIST was assessed by BICR in participants with PD-L1 positive tumors (CPS ≥1%) up through the final analysis database cut-off date of 26-Oct-2017. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Control | 3.3 |
| Pembrolizumab | 2.1 |
PFS Per RECIST 1.1 - Participants With Programmed Cell Death-Ligand (PD-L1) Positive Tumors
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, 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 demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had PD-L1 positive tumors (combined positive score [CPS] ≥1%) up through the primary analysis database cut-off date of 07-Sep-2016. (NCT02256436)
Timeframe: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
| Intervention | Months (Median) |
|---|
| Control | 3.2 |
| Pembrolizumab | 2.1 |
PFS Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
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, 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 demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. PFS per RECIST 1.1 was assessed by BICR in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) up through the primary analysis database cut-off date of 07-Sep-2016. (NCT02256436)
Timeframe: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
| Intervention | Months (Median) |
|---|
| Control | 3.1 |
| Pembrolizumab | 2.1 |
Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - All Participants
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 (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 demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was assessed by blinded independent central review (BICR) in all participants up through the primary analysis database cut-off date of 07-Sep-2016. (NCT02256436)
Timeframe: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
| Intervention | Months (Median) |
|---|
| Control | 3.3 |
| Pembrolizumab | 2.1 |
DOR Per RECIST 1.1 - All Participants
For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants based on BICR and was analyzed using the Kaplan-Meier method. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Control | 4.4 |
| Pembrolizumab | NA |
DOR Per RECIST 1.1 - Participants With PD-L1 Positive Tumors
For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had PD-L1 positive tumors (CPS ≥1%) based on BICR and was analyzed using the Kaplan-Meier method. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Control | NA |
| Pembrolizumab | NA |
Duration of Response (DOR) Per RECIST 1.1 - Participants With Strongly PD-L1 Positive Tumors
For participants who demonstrated a confirmed response (CR or PR) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. Per protocol, the DOR was to be censored at the date of the last tumor assessment for participants who had progressed or died after 2 or more missed visits, who had started a new anti-cancer treatment, who were lost to follow-up, or who had an ongoing response. DOR was assessed in all participants who had strongly PD-L1 positive tumors (CPS ≥10%) based on BICR and was analyzed using the Kaplan-Meier method. (NCT02256436)
Timeframe: Through final analysis database cut-off date of 26-Oct-2017 (Up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Control | 4.4 |
| Pembrolizumab | NA |
Overall Survival (OS) - All Participants
OS was defined as the time from randomization to death due to any cause. The OS was assessed in all participants up through the primary analysis database cut-off date of 07-Sep-2016. (NCT02256436)
Timeframe: Through primary analysis database cut-off date of 07-Sep-2016 (Up to approximately 20 months)
| Intervention | Months (Median) |
|---|
| Control | 7.4 |
| Pembrolizumab | 10.3 |
Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)
The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled from 0 (worst health imaginable) to 100 (best health imaginable). (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Change at Week 1 | Change at Week 13 | Change at Week 25 | Change at Week 37 | Change at Week 49 | Change at Week 61 | Change at Week 73 | Change at Week 85 |
|---|
| Placebo | 0.0 | 0.0 | -0.8 | -0.2 | 0.4 | -8.3 | 2.5 | -20.0 | -10.0 |
Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
FACT-P quality of life questionnaire is a multi-dimensional, self-reported quality of life instrument specifically designed for use with prostate cancer participants. It consists of 27 core items which assess participant function in four domains rated on 0 to 4 Likert-type scale: physical well-being (PWB) (7 items; 0 [worst] to 4 [better], score range 0-28), social/family well-being (SWB) (7 items; 0 [worst] to 4 [better], score range 0-28), emotional well-being (EWB) (6 items; 0 [worst] to 4 [better], score range 0-24), and functional well-being (FWB) (7 items; 0 [worst] to 4 [better], score range 0-28), which is further supplemented by 12 site-specific items to assess for prostate-related symptoms (Prostate Cancer Subscale [PCS] 12 items rated on Likert-type scale 0 [worst] to 4 [better], score range 0-48). The total domain scores and PCS subscale score are then combined to a global quality of life score ranging between 0 to 156; higher scores representing better quality of life. (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181
| Intervention | score on a scale (Mean) |
|---|
| EWB: Baseline | EWB: Change at Week 1 | EWB: Change at Week 13 | EWB: Change at Week 25 | EWB: Change at Week 37 | EWB: Change at Week 49 | EWB: Change at Week 61 | EWB: Change at Week 73 | EWB: Change at Week 85 | EWB: Change at Week 97 | EWB: Change at Week 109 | EWB: Change at Week 121 | EWB: Change at Week 133 | EWB: Change at Week 145 | EWB: Change at Week 157 | EWB: Change at Week 169 | EWB: Change at Week 181 | FWB: Baseline | FWB: Change at Week 1 | FWB: Change at Week 13 | FWB: Change at Week 25 | FWB: Change at Week 37 | FWB: Change at Week 49 | FWB: Change at Week 61 | FWB: Change at Week 73 | FWB: Change at Week 85 | FWB: Change at Week 97 | FWB: Change at Week 109 | FWB: Change at Week 121 | FWB: Change at Week 133 | FWB: Change at Week 145 | FWB: Change at Week 157 | FWB: Change at Week 169 | FWB: Change at Week 181 | Global Score: Baseline | Global Score: Change at Week 1 | Global Score: Change at Week 13 | Global Score: Change at Week 25 | Global Score: Change at Week 37 | Global Score: Change at Week 49 | Global Score: Change at Week 61 | Global Score: Change at Week 73 | Global Score: Change at Week 85 | Global Score: Change at Week 97 | Global Score: Change at Week 109 | Global Score: Change at Week 121 | Global Score: Change at Week 133 | Global Score: Change at Week 145 | Global Score: Change at Week 157 | Global Score: Change at Week 169 | Global Score: Change at Week 181 | PWB: Baseline | PWB: Change at Week 1 | PWB: Change at Week 13 | PWB: Change at Week 25 | PWB: Change at Week 37 | PWB: Change at Week 49 | PWB: Change at Week 61 | PWB: Change at Week 73 | PWB: Change at Week 85 | PWB: Change at Week 97 | PWB: Change at Week 109 | PWB: Change at Week 121 | PWB: Change at Week 133 | PWB: Change at Week 145 | PWB: Change at Week 157 | PWB: Change at Week 169 | PWB: Change at Week 181 | PCS: Baseline | PCS: Change at Week 1 | PCS: Change at Week 13 | PCS: Change at Week 25 | PCS: Change at Week 37 | PCS: Change at Week 49 | PCS: Change at Week 61 | PCS: Change at Week 73 | PCS: Change at Week 85 | PCS: Change at Week 97 | PCS: Change at Week 109 | PCS: Change at Week 121 | PCS: Change at Week 133 | PCS: Change at Week 145 | PCS: Change at Week 157 | PCS: Change at Week 169 | PCS: Change at Week 181 | SWB: Baseline | SWB: Change at Week 1 | SWB: Change at Week 13 | SWB: Change at Week 25 | SWB: Change at Week 37 | SWB: Change at Week 49 | SWB: Change at Week 61 | SWB: Change at Week 73 | SWB: Change at Week 85 | SWB: Change at Week 97 | SWB: Change at Week 109 | SWB: Change at Week 121 | SWB: Change at Week 133 | SWB: Change at Week 145 | SWB: Change at Week 157 | SWB: Change at Week 169 | SWB: Change at Week 181 |
|---|
| Enzalutamide | 0.00 | 0.00 | 1.15 | 0.69 | 1.91 | 1.22 | 0.59 | 1.69 | 1.00 | 3.90 | 2.93 | 4.00 | 2.00 | 2.00 | 2.00 | 1.00 | 2.00 | 0.0000 | 0.0000 | -1.8144 | -2.4472 | -1.5697 | -1.1579 | 0.0000 | -1.8182 | 1.2000 | -0.5000 | -1.3333 | -1.5000 | -0.5000 | -2.0000 | 0.0000 | -1.0000 | 0.0000 | 0.0000 | 0.0000 | -0.7836 | -5.9204 | -1.5351 | -4.4880 | -0.2957 | -0.3917 | 1.7636 | 6.2864 | -2.7333 | 4.0000 | -7.0000 | -11.0000 | -1.0000 | -10.0000 | -4.0000 | 0.0000 | 0.0000 | -1.3322 | -3.1317 | -2.1786 | -2.5316 | -1.3889 | -0.3636 | 1.0000 | 1.7500 | -0.6667 | -4.0000 | -4.5000 | -4.0000 | 0.0000 | -4.0000 | -2.0000 | 0.0000 | 0.0000 | 1.1842 | -0.4775 | -1.1433 | -1.8465 | 0.3690 | 0.9174 | 2.1636 | 3.8864 | -1.6667 | 2.0000 | -3.0000 | -5.0000 | 0.0000 | -3.0000 | -2.0000 | 0.0000 | 0.0000 | -0.1581 | -0.3634 | 0.8798 | -0.0719 | -0.8167 | -0.8182 | -3.6000 | -2.7500 | -2.0000 | 0.5000 | -1.0000 | -2.0000 | -3.0000 | -3.0000 | -2.0000 |
Time to Prostate-specific Antigen (PSA) Progression
Time to PSA progression, defined as the time from randomization (Period 2 Week 1) to the date of the first PSA value in Period 2 demonstrating progression (Period 2). The PSA progression date is defined as the date that a ≥ 25% increase and an absolute increase of ≥ 2 ng/mL above the nadir recorded in Period 2 is documented, which must be confirmed by a second consecutive value obtained at least 3 weeks later. (NCT02288247)
Timeframe: From date of randomization to the first PSA value (median duration: 35 weeks)
| Intervention | months (Median) |
|---|
| Enzalutamide | 8.44 |
| Placebo | 6.24 |
Change From Baseline in Functional Assessment of Cancer Therapy - Prostate (FACT-P)
FACT-P quality of life questionnaire is a multi-dimensional, self-reported quality of life instrument specifically designed for use with prostate cancer participants. It consists of 27 core items which assess participant function in four domains rated on 0 to 4 Likert-type scale: physical well-being (PWB) (7 items; 0 [worst] to 4 [better], score range 0-28), social/family well-being (SWB) (7 items; 0 [worst] to 4 [better], score range 0-28), emotional well-being (EWB) (6 items; 0 [worst] to 4 [better], score range 0-24), and functional well-being (FWB) (7 items; 0 [worst] to 4 [better], score range 0-28), which is further supplemented by 12 site-specific items to assess for prostate-related symptoms (Prostate Cancer Subscale [PCS] 12 items rated on Likert-type scale 0 [worst] to 4 [better], score range 0-48). The total domain scores and PCS subscale score are then combined to a global quality of life score ranging between 0 to 156; higher scores representing better quality of life. (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181
| Intervention | score on a scale (Mean) |
|---|
| EWB: Baseline | EWB: Change at Week 1 | EWB: Change at Week 13 | EWB: Change at Week 25 | EWB: Change at Week 37 | EWB: Change at Week 49 | EWB: Change at Week 61 | EWB: Change at Week 73 | EWB: Change at Week 85 | FWB: Baseline | FWB: Change at Week 1 | FWB: Change at Week 13 | FWB: Change at Week 25 | FWB: Change at Week 37 | FWB: Change at Week 49 | FWB: Change at Week 61 | FWB: Change at Week 73 | FWB: Change at Week 85 | Global Score: Baseline | Global Score: Change at Week 1 | Global Score: Change at Week 13 | Global Score: Change at Week 25 | Global Score: Change at Week 37 | Global Score: Change at Week 49 | Global Score: Change at Week 61 | PWB: Baseline | PWB: Change at Week 1 | PWB: Change at Week 13 | PWB: Change at Week 25 | PWB: Change at Week 37 | PWB: Change at Week 49 | PWB: Change at Week 61 | PWB: Change at Week 73 | PWB: Change at Week 85 | PCS: Baseline | PCS: Change at Week 1 | PCS: Change at Week 13 | PCS: Change at Week 25 | PCS: Change at Week 37 | PCS: Change at Week 49 | PCS: Change at Week 61 | SWB: Baseline | SWB: Change at Week 1 | SWB: Change at Week 13 | SWB: Change at Week 25 | SWB: Change at Week 37 | SWB: Change at Week 49 | SWB: Change at Week 61 | SWB: Change at Week 73 | SWB: Change at Week 85 |
|---|
| Placebo | 0.00 | 0.00 | 1.36 | 1.03 | 1.43 | 0.73 | 2.00 | -1.00 | -5.00 | 0.0000 | 0.0000 | -0.3121 | -0.8229 | -0.1459 | -1.3818 | -2.3333 | -2.0000 | 0.0000 | 0.0000 | 0.0000 | 1.7986 | 1.0762 | 0.1649 | -4.6202 | 6.0939 | 0.0000 | 0.0000 | -0.6347 | -0.4590 | -0.9556 | -1.3913 | 1.3333 | 3.0000 | 3.0000 | 0.0000 | 0.0000 | 1.6011 | 1.8632 | 0.6988 | -0.7223 | 4.2606 | 0.0000 | 0.0000 | -0.2953 | -0.0462 | -0.3963 | -0.7536 | 0.8333 | -24.0000 | -24.0000 |
Prostate-specific Antigen (PSA) Response
PSA response, defined as a decrease in percentage change from randomization (Period 2 Week 1) of 50% or more. PSA response was derived at Week 13 and at any time after randomization in Period 2. PSA response at any time is defined as a decrease in percentage change from randomization (Period 2 Week 1) at any time after randomization of 50% or more. Percentage of participants with PSA response was reported. (NCT02288247)
Timeframe: Randomization, Week 13, any time after randomization in Period 2 (median of 35 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Week 13 | Any time after randomization (median of 35 weeks) |
|---|
| Enzalutamide | 44.9 | 55.9 |
,| Placebo | 25.2 | 37.0 |
Change From Baseline in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)
The EQ-5D-5L VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled from 0 (worst health imaginable) to 100 (best health imaginable). (NCT02288247)
Timeframe: Period 2: Baseline, weeks 1, 13, 25, 37, 49, 61, 73, 85, 97, 109, 121, 133, 145, 157, 169, 181
| Intervention | score on a scale (Mean) |
|---|
| Baseline | Change at Week 1 | Change at Week 13 | Change at Week 25 | Change at Week 37 | Change at Week 49 | Change at Week 61 | Change at Week 73 | Change at Week 85 | Change at Week 97 | Change at Week 109 | Change at Week 121 | Change at Week 133 | Change at Week 145 | Change at Week 157 | Change at Week 169 | Change at Week 181 |
|---|
| Enzalutamide | 0.0 | 0.0 | 2.3 | -3.0 | -1.3 | -2.5 | 1.3 | -3.5 | 7.2 | 17.8 | 17.7 | -7.0 | 0.5 | 1.0 | -4.0 | 2.0 | -4.0 |
Objective Response Rate (ORR)
ORR, defined as the best overall radiographic response after randomization (Period 2 Week 1) as per Investigator assessments of response for soft tissue disease per RECIST 1.1, in participants who had a measurable tumor. ORR was reported as the percentage of participants with complete response (CR) or partial response (PR). CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. (NCT02288247)
Timeframe: From date of randomization up to median duration of 35 weeks
| Intervention | percentage of participants (Number) |
|---|
| Enzalutamide | 31.6 |
| Placebo | 25.9 |
Progression Free Survival (PFS)
PFS: time from randomization (Period 2 Week 1) to earliest progression event. Progression is defined as radiographic progression, unequivocal clinical progression, or death on study. Radiographic progression is defined for bone disease by appearance of ≥ 2 new lesions on whole-body radionuclide bone scan per Prostate Cancer Clinical Trials Working Group 2 (PCWG2) criteria (i.e., unconfirmed progressive disease) that needs to be confirmed in the next assessment (i.e., progressive disease in the next assessment) or for soft tissue disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Unequivocal clinical progression is defined as new onset cancer pain requiring chronic administration of opiate analgesia or deterioration from prostate cancer of Eastern Cooperative Oncology Group (ECOG) performance status score to ≥ 3, or initiation of subsequent lines of cytotoxic chemotherapy or radiation therapy or surgical intervention due to complications of tumor progression. (NCT02288247)
Timeframe: From date of randomization to the earliest of either documented disease progression (median duration: 35 weeks)
| Intervention | months (Median) |
|---|
| Enzalutamide | 9.53 |
| Placebo | 8.28 |
AUC0-infinity of Docetaxel
This outcome measure presents the AUC0-infinity of docetaxel in plasma in cycles 1 and 2. (NCT02300298)
Timeframe: just before administration of docetaxel administration -0:05 hours (h), at the end of infusion (1:00), and at timepoints after the first dose of docetaxel 1:30 h, 2, 3, 4, 7, 23:55, 47:55 h in cycle 1 and 2 (if administered)
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| Nintedanib Plus Docetaxel | 3320 | 3590 |
Maximum Measured Concentration (Cmax) of Nintedanib
This outcome measure presents the maximum measured concentration (Cmax) of nintedanib in plasma in cycle 1. (NCT02300298)
Timeframe: At 23:55 hours (h) after the first dose of docetaxel (which is 5 minutes prior to first dose of nintedanib) and at 25, 26, 27, 28, 30, 31, 34 and 47:55 h after first drug administration of docetaxel in cycle 1.
| Intervention | nanogram (ng)/ millilitre (mL) (Geometric Mean) |
|---|
| Nintedanib Plus Docetaxel | 65.1 |
Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 Extrapolated to Infinity (AUC0-infinity)
This outcome measure presents the Area under the concentration-time curve of nintedanib over the time interval from 0 extrapolated to infinity in plasma (AUC0-infinity) in cycle 1. (NCT02300298)
Timeframe: at 23:55 hours (h) after the first dose of docetaxel (which is 5 minutes prior to first dose of nintedanib) and at 25, 26, 27, 28, 30, 31, 34 and 47:55 h after first drug administration of docetaxel in cycle 1.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Nintedanib Plus Docetaxel | 381 |
Area Under the Concentration-time Curve of Nintedanib Over the Time Interval From 0 to Time of the Last Quantifiable Concentration (AUC0-tz)
This outcome measure presents the area under the concentration-time curve of nintedanib over the time interval from 0 to time of the last quantifiable concentration in plasma (AUC0-tz) in cycle 1. (NCT02300298)
Timeframe: At 23:55 hours (h) after the first dose of docetaxel (which is 5 minutes prior to first dose of nintedanib) and at 25, 26, 27, 28, 30, 31, 34 and 47:55 after first drug administration of docetaxel in cycle 1.
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Nintedanib Plus Docetaxel | 342 |
Number of Patients Experiencing Dose Limiting Toxicity (DLT) in Cycle 1
"DLT was defined as any of the following study drug related adverse events (AEs):~Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 non-haematological toxicity except transient electrolyte abnormality and isolated increase of gamma-glutamyltransferase (GGT); gastrointestinal toxicity, despite adequate supportive care~CTCAE grade 4 haematological toxicity; Neutrophil count decreased or white blood cell count (not associated with fever) for >7 days despite adequate supportive treatment~CTCAE grade 4 febrile neutropenia with fever ≥38.5 degrees~CTCAE grade ≥2 alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) increase in conjunction with CTCAE grade ≥2 total bilirubin increase~Inability to resume nintedanib dosing within 14 days after stopping Investigators judged clinically as DLT after dose reduction and severity medically notable (CTCAE, version 3). Sponsor with safety review committee was allowed to confirm the adequacy of this judgment." (NCT02300298)
Timeframe: Cycle 1, from first administration of study medication up to 21 days thereafter.
| Intervention | Participants (Number) |
|---|
| Total with DLTs - all grades | Total with DLTs - grade 1/2 | Total with DLTs - grade 3/4/5 | Hepatobiliary disorders (hep. dis.) - all grades | Hep. dis. - grade 1/2 | Hep. dis. - grade 3/4/5 | Hep. dis. - hyperbilirubinaemia - all grades | Hep. dis. - hyperbilirubinaemia - grade 1/2 | Hep. dis. - hyperbilirubinaemia - grades 3/4/5 | Investigations (inv.) - all grades | Inv. - grade 1/2 | Inv. - grade 3/4/5 | Inv. - ALT increased - all grades | Inv. - ALT increased - grades 1/2 | Inv. - ALT increased - grades 3/4/5 | Inv. - AST increased - all grades | Inv. - AST increased - grades 1/2 | Inv. - AST increased - grades 3/4/5 |
|---|
| Nintedanib Plus Docetaxel | 2 | 0 | 2 | 1 | 1 | 0 | 1 | 1 | 0 | 2 | 0 | 2 | 2 | 0 | 2 | 2 | 0 | 2 |
Cmax of Docetaxel
This outcome measure presents the Cmax of docetaxel in plasma in cycles 1 and 2. (NCT02300298)
Timeframe: just before administration of docetaxel administration -0:05 hours (h), at the end of infusion (1:00), and at timepoints after the first dose of docetaxel 1:30 h, 2, 3, 4, 7, 23:55, 47:55 h in cycle 1 and 2 (if administered)
| Intervention | nanogram (ng)/ millilitre (mL) (Geometric Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| Nintedanib Plus Docetaxel | 2710 | 2680 |
AUC0-tz of Docetaxel
This outcome measure presents AUC0-tz of docetaxel in plasma in cycles 1 and 2. (NCT02300298)
Timeframe: just before administration of docetaxel administration -0:05 hours (h), at the end of infusion (1:00), and at timepoints after the first dose of docetaxel 1:30 h, 2, 3, 4, 7, 23:55, 47:55 h in cycle 1 and 2 (if administered)
| Intervention | ng*h/mL (Geometric Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| Nintedanib Plus Docetaxel | 3080 | 3320 |
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Physical Functioning Scale
The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS. (NCT02302807)
Timeframe: Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)
| Intervention | units of a scale (Mean) |
|---|
| Baseline (Cycle 1, Day 1) | Change from baseline: Cycle 2, Day 1 | Change from baseline: Cycle 3, Day 1 | Change from baseline: Cycle 4, Day 1 | Change from baseline: Cycle 12, Day 1 | Change from baseline: Cycle 20, Day 1 | Change from baseline: Cycle 28, Day 1 | Change from baseline: Treatment Discont. Visit |
|---|
| Atezolizumab | 76.37 | -7.56 | -7.06 | -3.81 | 0.89 | 3.48 | 3.51 | -20.19 |
,| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 74.23 | -4.80 | -5.64 | -4.41 | -6.97 | -3.03 | -18.67 | -15.58 |
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Global Health Status Scale
The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS. (NCT02302807)
Timeframe: Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)
| Intervention | units of a scale (Mean) |
|---|
| Baseline (Cycle 1, Day 1) | Change from baseline: Cycle 2, Day 1 | Change from baseline: Cycle 3, Day 1 | Change from baseline: Cycle 4, Day 1 | Change from baseline: Cycle 12, Day 1 | Change from baseline: Cycle 20, Day 1 | Change from baseline: Cycle 28, Day 1 | Change from baseline:Treatment Discont. Visit |
|---|
| Atezolizumab | 64.19 | -6.18 | -4.67 | -0.53 | -0.56 | 1.10 | -5.26 | -16.71 |
,| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 61.49 | -5.47 | -3.76 | -1.48 | -3.95 | -2.27 | -11.67 | -10.77 |
Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Score: Fatigue Symptom Scale
The EORTC QLQ-C30 includes five functional scales (physical, role, cognitive, emotional, social); a global health status (GHS)/quality of life (QoL) scale; and items measuring fatigue, pain, nausea and vomiting, dyspnea, appetite loss, sleep disturbance, constipation, diarrhea, and financial difficulties. The score range for each scale and single-item measure is 0 to 100, where higher scores indicate a higher response level (i.e., better functioning, better QoL, worse symptoms). Key scales included physical functioning, and fatigue, and GHS. (NCT02302807)
Timeframe: Cycle 1 Day 1 (prior to any health care interaction), on Day 1 of each subsequent cycle, and at 30 days after the last treatment dose (Up to approximately 25 months; each cycle is 21 days)
| Intervention | units of a scale (Mean) |
|---|
| Fatigue Symptom: Baseline (Cycle 1, Day 1) | Fatigue Symptom: Cycle 2, Day 1 | Change from baseline: Cycle 3, Day 1 | Change from baseline: Cycle 4, Day 1 | Change from baseline: Cycle 12, Day 1 | Change from baseline: Cycle 20, Day 1 | Change from baseline: Cycle 28, Day 1 | Change from baseline: Treatment Discont. Visit |
|---|
| Atezolizumab | 32.87 | 10.56 | 9.41 | 3.67 | -0.95 | -8.05 | -12.28 | 19.60 |
,| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 34.67 | 10.71 | 11.04 | 7.48 | 5.70 | 11.11 | 15.56 | 17.27 |
Unconfirmed Duration of Response (DOR) as Determined by the Investigator With Use of RECIST v1.1
DOR was defined as the time from first occurrence of a CR or PR, whichever came first, to first documented PD or death, whichever occurred first. Disease progression was determined on the basis of investigator assessment with use of RECIST v1.1. CR: disappearance of all target lesions. 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. 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). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of >/= 5 mm. (NCT02302807)
Timeframe: Up to approximately 25 months after first participant enrolled
| Intervention | months (Median) |
|---|
| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 5.3 |
| Atezolizumab | 21.7 |
| IC2/3 Chemotherapy | 6.4 |
| IC2/3 Atezolizumab | 13.0 |
| IC1/2/3 Chemotherapy | 5.5 |
| IC1/2/3 Atezolizumab | 13 |
Progression-free Survival (PFS) as Determined by the Investigator With Use of RECIST v1.1
PFS was defined as the time between the date of randomization and the date of first documented progression of disease (PD) or death, whichever occurred first. PD was determined on the basis of investigator assessment with use of RECIST v1.1. 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). In addition to the relative increase of 20%, the sum of diameters had to demonstrate an absolute increase of >/= 5 millimeters (mm). (NCT02302807)
Timeframe: Up to approximately 25 months after first participant enrolled
| Intervention | months (Median) |
|---|
| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 4.0 |
| Atezolizumab | 2.1 |
| IC2/3 Chemotherapy | 4.2 |
| IC2/3 Atezolizumab | 2.4 |
| IC1/2/3 Chemotherapy | 4.1 |
| IC1/2/3 Atezolizumab | 2.1 |
Percentage of Participants With Post-Baseline Anti-therapeutic Antibodies (ATA) to Atezolizumab
Participants were considered post-baseline ATA positive if they had post-baseline ATAs to Atezolizumab that were treatment-induced or treatment-enhanced. Participants had treatment-induced ATAs if they had a baseline-negative ATA result and developed ATAs at any time after initial drug administration. Participants had treatment-enhanced ATAs if they had a baseline-positive ATA result that showed an enhanced signal that was >/= 0.60 titer units at any time after initial drug initiation. (NCT02302807)
Timeframe: Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)
| Intervention | percentage of participants (Number) |
|---|
| Atezolizumab | 33.3 |
| IC1/2/3 Atezolizumab | 35.0 |
| IC2/3 Atezolizumab | 33.0 |
Percentage of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable 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. Preexisting conditions which worsen during a study are also considered as adverse events. (NCT02302807)
Timeframe: Up to approximately 46 months after first participant enrolled
| Intervention | percentage (Number) |
|---|
| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 98.2 |
| Atezolizumab | 95.0 |
| IC2/3 Chemotherapy | 98.2 |
| IC2/3 Atezolizumab | 96.5 |
| IC1/2/3 Chemotherapy | 98.7 |
| IC1/2/3 Atezolizumab | 96.2 |
Overall Survival (OS)
OS was defined as time from randomization to death from any cause. (NCT02302807)
Timeframe: Between randomization and death due to any cause, up to approximately 25 months after first participant enrolled
| Intervention | Months (Median) |
|---|
| IC2/3 Chemotherapy | 10.6 |
| IC2/3 Atezolizumab | 11.1 |
| IC1/2/3 Chemotherapy | 8.2 |
| IC1/2/3 Atezolizumab | 8.9 |
| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 8.0 |
| Atezolizumab | 8.6 |
Maximum Observed Serum Atezolizumab Concentration (Cmax)
Cmax was measured for all participants that received at least one dose of Atezolizumab. (NCT02302807)
Timeframe: 30 minutes post dose on Day 1 of Cycles 1
| Intervention | mcg/mL (Geometric Mean) |
|---|
| Atezolizumab | 334 |
Percentage of Participants With Unconfirmed Objective Response Rate (ORR) as Determined by the Investigator With Use of Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST v1.1)
ORR was defined as the percentage of participants, who had an objective response. Objective response was defined as either a complete response (CR) or partial response (PR) as determined by the investigator with use of Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). Objective response in this study did not need to be a confirmed response. CR: disappearance of all target lesions. 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. ORR=CR+PR (NCT02302807)
Timeframe: Up to approximately 25 months after first participant enrolled
| Intervention | Percentage of participants (Number) |
|---|
| Chemotherapy (Vinflunine, Paclitaxel, or Docetaxel) | 20.8 |
| Atezolizumab | 15.4 |
| IC2/3 Chemotherapy | 29.3 |
| IC2/3 Atezolizumab | 26.5 |
| IC1/2/3 Chemotherapy | 22.2 |
| IC1/2/3 Atezolizumab | 16.3 |
Minimum Observed Serum Atezolizumab Concentration (Cmin)
Cmin was measured for all participants that received at least one dose of Atezolizumab. (NCT02302807)
Timeframe: Predose (0 hours) on Day 1 of Cycles 1, 2, 3, 4 and every 8 cycles thereafter; at treatment discontinuation (up to 25 months); at 120 days after last dose of atezolizumab (up to 25 months; each cycle is 21 days)
| Intervention | mcg/mL (Geometric Mean) |
|---|
| 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 |
|---|
| Atezolizumab | 67.5 | 95.1 | 122 | 159 | 190 | 190 | 223 |
Overall Survival (OS)
OS was calculated as 1+ the number of days from randomization to death due to any cause. Patients without a documented date of death were censored on the date the patient was last known to be alive. (NCT02322281)
Timeframe: Cycle 1 Day 1 to date of death, assessed up to 3 years
| Intervention | Days (Median) |
|---|
| Rociletinib 500 mg BID | 665 |
| Rociletinib 625 mg BID | 541 |
| Chemotherapy | 348 |
Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)
PFS was calculated as 1+ the number of days from the date of randomization to documented radiographic progression as determined by the investigator, or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter 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. (NCT02322281)
Timeframe: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for PFS.
| Intervention | Days (Median) |
|---|
| Rociletinib 500 mg BID | 125.0 |
| Rociletinib 625 mg BID | 166.0 |
| Chemotherapy | 77.0 |
Percentage of Participants With Confirmed Response
Percentage of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: 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),at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Overall Response (OR),is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria. (NCT02322281)
Timeframe: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for best overall confirmed response.
| Intervention | percentage of participants (Number) |
|---|
| Rociletinib 500 mg BID | 17.0 |
| Rociletinib 625 mg BID | 18.2 |
| Chemotherapy | 8.2 |
Duration of Response (DOR) According to RECIST Version 1.1 as Determined by Investigator Assessment
DOR in patients with confirmed response per investigator. The DOR for complete response (CR) and partial response (PR) was measured from date that any of these best responses is first recorded until first date that progressive disease (PD) is objectively documented. For patients who continue treatment post-progression, the first date of progression was used for the analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR is at least a 30% decrease in sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Overall Response is the best response from start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). (NCT02322281)
Timeframe: Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
| Intervention | Days (Median) |
|---|
| Rociletinib 500 mg BID | 335.0 |
| Rociletinib 625 mg BID | 275.0 |
| Chemotherapy | 206.0 |
Plasma PK for Patients Treated With Rociletinib Based on Sparse Sampling
Blood samples were drawn for PK analysis at 21 ± 3 day intervals for the first 6 months (Day 1 of Cycles 2 to 7 inclusive). The sample could be taken predose or postdose. Plasma concentrations are presented for Rociletinib and 3 metabolites (M460, M502, M544). (NCT02322281)
Timeframe: Cycles 2 Day 1 to Cycle 7 Day 1, or approximately 6 months
| Intervention | Plasma concentration (ng/mL) (Median) |
|---|
| Rociletinib | M460 | M502 | M544 |
|---|
| Rociletinib 500 mg BID | 80.4 | 20.0 | 573.0 | 765.0 |
,| Rociletinib 625 mg BID | 207.0 | 555.0 | 3260.0 | 525.0 |
Disease Control Rate (DCR) Using RECIST 1.1 Criteria
DCR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. (NCT02324543)
Timeframe: 43 months
| Intervention | percentage of participants (Number) |
|---|
| Phase 2 | 87 |
Response Rate (RR) Using RECIST 1.1 Criteria
RR is defined as the percentage of participants achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions, progressive disease (PD) is >20% increase in sum of diameters of target lesions, stable disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. (NCT02324543)
Timeframe: 43 months
| Intervention | percentage of participants (Number) |
|---|
| Phase 2 | 57 |
Progression-free Survival (PFS) Using RECIST 1.1 Criteria
PFS is defined as the number of months from the date of first dose to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve. (NCT02324543)
Timeframe: 5 years
| Intervention | Months (Median) |
|---|
| Phase 2 | 8.34 |
Overall Survival (OS) Rate at 9 Months
OS will be measured as the percentage of subjects alive at 9 months. (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. (Phase 2 data only) (NCT02324543)
Timeframe: 9 months
| Intervention | percentage of participants (Number) |
|---|
| Phase 2 | 57 |
Overall Survival (OS)
OS will be measured (in months) from date of first dose until death or end of follow-up (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve. (NCT02324543)
Timeframe: 5 years
| Intervention | Months (Median) |
|---|
| Phase 2 | 11.02 |
Maximum Tolerated Dose (MTD) of Gemcitabine
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. (NCT02324543)
Timeframe: 28 days
| Intervention | mg/m^2 (Number) |
|---|
| Phase 1 | 500 |
Maximum Tolerated Dose (MTD) of Docetaxel
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. (NCT02324543)
Timeframe: 28 days
| Intervention | mg/m^2 (Number) |
|---|
| Phase 1 | 20 |
Maximum Tolerated Dose (MTD) of Irinotecan
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. (NCT02324543)
Timeframe: 28 days
| Intervention | mg/m^2 (Number) |
|---|
| Phase 1 | 20 |
Maximum Tolerated Dose (MTD) of Cisplatin
Dose escalation (phase I portion of the trial only) to determine the MTD in mg/m^2. (NCT02324543)
Timeframe: 28 days
| Intervention | mg/m^2 (Number) |
|---|
| Phase 1 | 20 |
Maximum Tolerated Dose (MTD) of Capecitabine
Dose escalation (phase I portion of the trial only) to determine the MTD in mg for twice daily (BID) use. (NCT02324543)
Timeframe: 28 days
| Intervention | mg (Number) |
|---|
| Phase 1 | 500 |
Number of Participants With the Indicated Type of Adverse Events for PEGPH20 and Docetaxel
Throughout the Treatment Period, the assessment of safety was based on AEs, including deaths, non-serious AEs, and serious adverse events, AEs leading to discontinuation of study treatment, and results of vital sign measurements and clinical laboratory assessments (including hematology, clinical chemistry, coagulation parameters, and urinalysis). Additionally, thromboembolic (TE) events were deemed by the Sponsor as AEs of special interest. AEs and laboratory values were graded for severity using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. (NCT02346370)
Timeframe: From date of first dose until 30 days after the last dose of study treatment, up to approximately 1 year 10 months
| Intervention | Participants (Count of Participants) |
|---|
| AEs greater than or equal to grade 3 | PEGPH20-related AEs | Docetaxel-related AEs | AEs with outcome of death | SAEs | Treatment-related SAEs | AEs leading to discontinuation of study drug |
|---|
| Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel | 5 | 6 | 7 | 0 | 3 | 1 | 1 |
,| Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel | 4 | 4 | 4 | 0 | 3 | 2 | 1 |
,| Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel | 3 | 4 | 4 | 0 | 1 | 1 | 2 |
Number of Dose Limiting Toxicities (DLTs)
DLTs were defined as adverse events (AEs) that occurred during Cycle 1 in the Dose Escalation portion of the study, and deemed by the Investigator as related to study treatment. (NCT02346370)
Timeframe: Cycle 1 (Day 1 through Day 21) (1 Cycle = 21 days)
| Intervention | DLTs (Number) |
|---|
| Neutropenia | Gastroenteritis Escherichia coli | Sepsis | Deep vein thrombosis |
|---|
| Cohort 1: 1.6 ug/kg PEGPH20 + Docetaxel | 0 | 0 | 0 | 0 |
,| Cohort 2: 3.0 ug/kg PEGPH20 + Docetaxel | 1 | 1 | 1 | 1 |
,| Cohort 3: 2.2 ug/kg PEGPH20 + Docetaxel | 0 | 0 | 0 | 1 |
Progression Free Survival by RECIST 1.1
(NCT02358473)
Timeframe: One year
| Intervention | months (Median) |
|---|
| Mogamulizumab + Docetaxel | 1.87 |
Overall Survival
(NCT02358473)
Timeframe: One year
| Intervention | months (Median) |
|---|
| Mogamulizumab + Docetaxel | 8.88 |
Overall Response Rate
(NCT02358473)
Timeframe: One year
| Intervention | Participants (Count of Participants) |
|---|
| Mogamulizumab + Docetaxel | 0 |
Number of Subjects Reporting Serious Adverse Events
(NCT02358473)
Timeframe: Screening through 90 days after the last dose of study medication
| Intervention | Participants (Count of Participants) |
|---|
| Mogamulizumab + Docetaxel | 6 |
Number of Subjects Reporting Adverse Events
(NCT02358473)
Timeframe: Screening through 90 days after the last dose of study medication
| Intervention | Participants (Count of Participants) |
|---|
| Mogamulizumab + Docetaxel | 13 |
Number of Subjects Experiencing Dose-limiting Toxicity
(NCT02358473)
Timeframe: First dose of study medications through 4 weeks after the last dose of study medication
| Intervention | Participants (Count of Participants) |
|---|
| Mogamulizumab + Docetaxel | 1 |
The Number of Patients With Tumor Size Reduction (Objective Response Rate)
Objective response rate is the sum of partial responses plus complete responses and will be assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) 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. (NCT02358863)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Chemotherapy | 0 |
Objective Response Rate
"Objective Response Rate (ORR) is defined as the proportion of patients a best overall response characterised as either a Complete Response (CR) or Partial Response (PR), as defined according to RECIST v1.1 guidelines, relative to the total number of evaluable patients.~Complete Response (CR) is defined as disappearance of all lesions and pathologic lymph nodes.~Partial Response (PR) is defined as >=30% decrease in the sum of the longest diameter of target lesions" (NCT02387216)
Timeframe: Randomization through end of study up to 3 years, 11 months (the study terminated prematurely)
| Intervention | Participants (Count of Participants) |
|---|
| Objective Response | Partial Response (PR) | Stable Disease (SD) | Progressive Disease | Not Evaluable | No Evaluation |
|---|
| Arm A (Experimental): MM-121 in Combination With Docetaxel | 14 | 14 | 39 | 12 | 1 | 5 |
,| Arm B (Comparator): Docetaxel Alone | 2 | 2 | 26 | 5 | 1 | 4 |
Number of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone
Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration (NCT02387216)
Timeframe: TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months
| Intervention | participants (Number) |
|---|
| Patients with any TEAE-Related | Patients with any TEAE-Serious Adverse event | Patients with any NCI-CTCAE Grade 3 or Higher |
|---|
| Arm A (Experimental): MM-121 in Combination With Docetaxel | 99 | 40 | 76 |
,| Arm B (Comparator): Docetaxel Alone | 45 | 15 | 31 |
Percentage of Participants With Treatment-emergent Adverse Events Reported With the Combination of MM-121 With Docetaxel Versus Docetaxel Alone
Treatment-emergent adverse events (TEAEs) are defined as any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration (NCT02387216)
Timeframe: TEAEs were collected through the study completion (02 Jan 2019), up to 3 years, 11 months
| Intervention | percentage of participants (Number) |
|---|
| TEAE-Related | TEAE-Serious Adverse event | NCI-CTCAE Grade 3 or Higher |
|---|
| Arm A (Experimental): MM-121 in Combination With Docetaxel | 96.1 | 38.8 | 73.8 |
,| Arm B (Comparator): Docetaxel Alone | 91.8 | 30.6 | 63.3 |
Time to Progression
Time to Progression (TTP) is defined as the time from the date of randomization to the date of objective tumor progression. In the actual analysis, duration of response (DOR) was analysed. (NCT02387216)
Timeframe: Randomization to date of objective tumor progression up to 3 years, 11 months (the study terminated prematurely)
| Intervention | months (Median) |
|---|
| Arm A (Experimental): MM-121 in Combination With Docetaxel | 3.0 |
| Arm B (Comparator): Docetaxel Alone | NA |
Progression Free Survival
"Progression Free Survival is defined as the time from randomization to the first documented radiographical progression of disease using RECIST v.1.1, or death from any cause, whichever came first based on investigator assessment.~Patients that do not experience progression or death at the time of analysis were to be progression censored at the date of last valid tumor assessment. Progression-free survival time distribution and median survival for each treatment group were analyzed using the Kaplan-Meier method. Tumor response was evaluated by the local radiologist according to RECIST version 1.1 to establish disease progression by CT or MRI." (NCT02387216)
Timeframe: Randomization until progression of disease or death due to any cause within 3 years,11 months (the study terminated prematurely)
| Intervention | months (Median) |
|---|
| Arm A (Experimental): MM-121 in Combination With Docetaxel | 3.4 |
| Arm B (Comparator): Docetaxel Alone | 4.1 |
Overall Survival
Overall Survival (OS) is defined as the time from the date of randomization to the date of death from any cause (NCT02387216)
Timeframe: From date of randomization until the date of death from any cause assessed upto 3 years,11 months (the study terminated prematurely)
| Intervention | months (Median) |
|---|
| Arm A (Experimental): MM-121 in Combination With Docetaxel | 7.7 |
| Arm B (Comparator): Docetaxel Alone | 8.4 |
Number of Participants With Significant Change in Physical Examination Reported as Adverse Events in Phase 1b
Physical examination consists of examinations of the following body systems: (1) eyes; (2) ears, nose, throat; (3) cardiovascular system; (4) respiratory system; (5) gastrointestinal system; (6) dermatologic system; (7) extremities; (8) musculoskeletal system; (9) nervous system; (10) lymph nodes; and (11) physical examinations other than body systems described in (1) to (10). (NCT02393209)
Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
| Intervention | participants (Number) |
|---|
| Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 | 0 |
| Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 | 1 |
Recommended Phase 2 Dose of TAK-117 in Phase 1b
The recommended phase 2 dose was determined in Phase 1b based on participant dose-limiting toxicities and the maximum tolerated dose. (NCT02393209)
Timeframe: Cycle 1 (Up to Day 21)
| Intervention | mg (Number) |
|---|
| TAK-117 + Docetaxel | 200 |
Number of Participants With Clinically Significant Change in Clinical Laboratory Tests Reported as Adverse Events in Phase 1b
The number of participants with any markedly abnormal standard safety laboratory values (Chemistry, Hematology and Urinalysis) collected throughout study. (NCT02393209)
Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
| Intervention | participants (Number) |
|---|
| Anemia | Hypokalemia | Hypomagnesemia | Hypophosphatemia | Aspartate aminotransferase increased | Febrile neutropenia | Hyponatremia | Hyperglycemia | Leukopenia | Pancytopenia | Thrombocytopenia | Blood creatinine increased | Alanine aminotransferase increased | Blood cholesterol increased | Neutrophil count decreased | White blood cell count decreased | Hyperkalaemia | Hypernatraemia | Hypoalbuminaemia | Hypocalcaemia |
|---|
| Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 | 2 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
,| Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 | 2 | 3 | 3 | 3 | 2 | 2 | 2 | 2 | 1 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 |
Number of Participants With Electrocardiogram (ECG) Findings Reported as Adverse Events in Phase 1b
A standard 12-lead ECG was performed. (NCT02393209)
Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
| Intervention | participants (Number) |
|---|
| Bradycardia | Tachycardia |
|---|
| Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 | 1 | 0 |
,| Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 | 0 | 1 |
Number of Participants With Significant Change in Vital Signs Reported as Adverse Events in Phase 1b
Clinically significant change from baseline in vital sign measures will be assessed. Vital sign measurements included measurements of diastolic and systolic blood pressure, heart rate, and temperature. (NCT02393209)
Timeframe: First dose of study drug through 30 days after the last dose of study drug (Up to Day 223)
| Intervention | participants (Number) |
|---|
| Bradycardia | Sinus tachycardia |
|---|
| Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 | 1 | 0 |
,| Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 | 0 | 1 |
Number of Participants With Dose-Limiting Toxicity (DLT) in Phase 1b
DLT was evaluated according to National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk. (NCT02393209)
Timeframe: Cycle 1 (Up to Day 21)
| Intervention | participants (Number) |
|---|
| Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 | 0 |
| Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 | 1 |
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) in Phase 1b
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. A serious adverse event (SAE) is any untoward medical occurrence or effect 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 is medically important due to other reasons than the above mentioned criteria. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug. (NCT02393209)
Timeframe: From first dose of study drug to 30 days after last dose of study drug (Up to Day 223)
| Intervention | participants (Number) |
|---|
| TEAEs | SAEs |
|---|
| Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 | 6 | 5 |
,| Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 | 8 | 6 |
TAK-117 Plasma Concentration in Phase 1b
(NCT02393209)
Timeframe: Cycle 1 Day 1 pre-dose and 0.5, 1, 2, 4, 6, 8 and 24 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| Predose | 0.5 Hour Postdose | 1 Hour Postdose | 2 Hours Postdose | 4 Hours Postdose | 6 Hours Postdose | 8 Hours Postdose | 24 Hours Postdose |
|---|
| Phase 1 - TAK-117 200 mg + Docetaxel 36 mg/m^2 | 114.00 | 1208.60 | 1907.00 | 2597.83 | 2477.50 | 2143.00 | 1902.50 | 652.17 |
,| Phase 1 - TAK-117 300 mg + Docetaxel 36 mg/m^2 | 0.00 | 847.39 | 1973.29 | 3021.43 | 4185.71 | 3648.57 | 3677.14 | 1771.57 |
Maximum Tolerated Dose (MTD) of TAK-117 in Combination With Docetaxel 36 mg/m^2 in Phase 1b
The MTD is defined as the dose of TAK-117 in combination with docetaxel 36 mg/m^2 at which 1 of 6 evaluable participants experience DLT. DLT was evaluated according to NCI CTCAE version 4.03 and was defined as any of the following events: 1. Grade 4 neutropenia or thrombocytopenia lasting ≥7 consecutive days; 2. Grade 4 neutropenia with fever and/or infection; 3. Platelet count <10,000/mm^3; 4. ≥Grade 3 thrombocytopenia with bleeding; 5. Any other ≥Grade 4 hematologic toxicity; 6. Any other ≥Grade 3 nonhematologic toxicity, with following exceptions: ≥Grade 3 arthralgia/myalgia, ≥Grade 3 nausea/emesis, ≥Grade 3 diarrhoea, Grade 3 fatigue, Grade 3 Rash, Grade 3 nonhematological toxicity that could be controlled to ≤Grade 1 with appropriate treatment; 7. Inability to administer at least 75% of planned doses; 8. Clinically significant occurrence per investigator that is a safety risk. (NCT02393209)
Timeframe: Cycle 1 (Up to Day 21)
| Intervention | mg (Number) |
|---|
| TAK-117 + Docetaxel | 300 |
Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
Cmax was defined as the maximum observed plasma concentration. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
| Intervention | ng/mL (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 137 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 199 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 234 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 214 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 259 |
Part 3: CL/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
CL/F was defined as the apparent oral dose clearance. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | L/hr (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 8.03 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 13.4 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 24.5 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 12.7 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 8.26 |
Part 3: AUClast of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
AUClast was defined as the area under the plasma or serum concentration-time curve from the time of dosing to the last measurable concentration. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
| Intervention | hr*ng/mL (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 1480 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 1880 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 2890 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 1890 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 2040 |
Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | hr*ng/mL (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 2400 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 2400 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 1650 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 2910 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 3440 |
Part 3: AUC0-24 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
| Intervention | hr*ng/mL (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 1550 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 1910 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 2920 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 1890 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 1890 |
Part 3: Accumulation Ratio of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
The accumulation ratio was defined as the ratio of the accumulation of a drug under steady-state conditions as compared to a single dose. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | ratio (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 1.65 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 1.53 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 0.604 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 1.52 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 1.90 |
Part 2: Overall Response Rate (ORR)
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. (NCT02393248)
Timeframe: up to 126 days
| Intervention | percentage of participants (Number) |
|---|
| Part 2: Intermittent Pemigatinib 9 mg QD | 25.0 |
| Part 2: Intermittent Pemigatinib 13.5 mg QD | 4.5 |
| Part 2: Continuous Pemigatinib 9 mg QD | 0.0 |
| Part 2: Continuous Pemigatinib 13.5 mg QD | 30.0 |
| Part 2: Continuous Pemigatinib 20 mg QD | 0.0 |
Parts 1 and 2: Tmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
tmax was defined as the time to the maximum observed plasma concentration. (NCT02393248)
Timeframe: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
| Intervention | hr (Median) |
|---|
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fasted | 1.58 |
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fed | 4.02 |
Parts 1 and 2: CL/F Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
CL/F was defined as the apparent oral dose clearance. (NCT02393248)
Timeframe: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
| Intervention | L/hr (Mean) |
|---|
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fasted | 12.4 |
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fed | 11.3 |
Parts 1 and 2: CL/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
CL/F was defined as the apparent oral dose clearance. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | Liters per hr (L/hr) (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 9.86 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 12.8 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 5.93 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 12.0 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 15.7 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 11.9 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 10.3 |
Parts 1 and 2: AUClast After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
AUClast was defined as the area under the plasma or serum concentration-time curve from the time of dosing to the last measurable concentration. (NCT02393248)
Timeframe: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
| Intervention | hr*ng/mL (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 190 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 68.8 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 1010 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 641 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 1140 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 1820 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 2510 |
Parts 1 and 2: AUC0-24 Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose. (NCT02393248)
Timeframe: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
| Intervention | hr*ng/mL (Mean) |
|---|
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fasted | 2580 |
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fed | 2910 |
Emax Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
Emax was defined as the maximum degree of increasing of serum phosphate by pemigatinib. (NCT02393248)
Timeframe: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
| Intervention | mg/dL (Geometric Mean) |
|---|
| Parts 1 and 2: Intermittent or Continuous Pemigatinib | 5.76 |
Highest Serum Phosphate Concentration Following Pemigatinib as Monotherapy in Parts 1 and 2
Serum phosphate concentration was assessed throughout Parts 1 and 2. (NCT02393248)
Timeframe: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
| Intervention | mg/dL (Number) |
|---|
| Minimum value in range of highest values for all participants | Maximum value in range of highest values for all participants |
|---|
| Parts 1 and 2: Intermittent or Continuous Pemigatinib | 3.5 | 11.2 |
Parts 1 and 2: Vz/F Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
Vz/F was defined as the apparent volume of distribution. (NCT02393248)
Timeframe: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
| Intervention | Liters (Mean) |
|---|
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fasted | 307 |
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fed | 364 |
Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | hr*ng/mL (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 208 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 322 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 1380 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 1080 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 2180 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 3010 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 4350 |
Parts 1 and 2: AUC0-24 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
AUC0-24 was defined as the area under the plasma or serum concentration-time curve from time 0 to 24 hours post-dose. (NCT02393248)
Timeframe: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
| Intervention | hr*ng/mL (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 191 |
| Part 1: Intermittent Pemigatinib 2 mg QD | NA |
| Part 1: Intermittent Pemigatinib 4 mg QD | 1010 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 644 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 1150 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 1840 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 2850 |
Parts 1 and 2: Accumulation Ratio After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
The accumulation ratio was defined as the ratio of the accumulation of a drug under steady-state conditions as compared to a single dose. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | ratio (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 1.09 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 1.64 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 1.36 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 1.67 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 1.71 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 1.69 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 1.76 |
EC50 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
EC50 was defined as the pemigatinib steady-state area under the plasma or serum concentration-time curve that increases 50% of serum phosphate. (NCT02393248)
Timeframe: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
| Intervention | hours*nanomoles (Geometric Mean) |
|---|
| Parts 1 and 2: Intermittent or Continuous Pemigatinib | 1573 |
Parts 1 and 2 Combined: Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
Adverse events were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after a participant provided informed consent. Abnormal laboratory values or test results that occurred after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). TEAEs were defined as adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last dose of study drug. (NCT02393248)
Timeframe: up to 763 days
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: Intermittent Pemigatinib 1/2/4 mg QD | 3 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 3 |
| Parts 1 and 2: Intermittent Pemigatinib 9 mg QD | 7 |
| Parts 1 and 2: Intermittent Pemigatinib 13.5 mg QD | 50 |
| Part 1: Intermittent Pemigatinib 20 mg QD | 6 |
| Parts 1 and 2: Continuous Pemigatinib 9 mg QD | 14 |
| Parts 1 and 2: Continuous Pemigatinib 13.5 mg QD | 30 |
| Parts 1 and 2: Continuous Pemigatinib 20 mg QD | 15 |
| Part 1: Continuous Pemigatinib 7.5 mg BID | 4 |
| Part 1: Continuous Pemigatinib 10 mg BID | 3 |
Part 3: Vz/F of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Vz/F was defined as the apparent volume of distribution. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | Liters (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 177 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 303 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 376 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 227 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 182 |
Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
tmax was defined as the time to the maximum observed plasma concentration. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | hr (Median) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 5.78 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 1.08 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 1.50 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 1.90 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 0.583 |
Part 3: Tmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 1
tmax was defined as the time to the maximum observed plasma concentration. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 1
| Intervention | hr (Median) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 1.98 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 1.05 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 2.00 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 1.00 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 0.783 |
Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
tmax was defined as the time to the maximum observed plasma concentration. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | hr (Median) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 1.07 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 3.98 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 2.02 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 1.58 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 1.00 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 1.13 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 1.12 |
Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
Cmax was defined as the maximum observed plasma concentration. (NCT02393248)
Timeframe: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
| Intervention | nanograms per milliliter (ng/mL) (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 25.3 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 13.6 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 109 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 64.6 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 139 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 196 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 300 |
Part 3: Number of Participants With Any TEAE
Adverse events were defined as the appearance of (or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that occurred after a participant provided informed consent. Abnormal laboratory values or test results that occurred after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). TEAEs were defined as adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last dose of study drug. (NCT02393248)
Timeframe: up to 869 days
| Intervention | Participants (Count of Participants) |
|---|
| Part 3: Gem/Cis/Intermittent Pemigatinib 9 mg | 1 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 7 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 6 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 7 |
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 3 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 14 |
| Part 3: Pem/Continuous Pemigatinib 13.5 mg | 9 |
| Part 3: Ref/Continuous Pemigatinib 9 mg | 7 |
| Part 3: Ref/Continuous Pemigatinib 13.5 mg | 9 |
| Part 3: Ref/Continuous Pemigatinib 20 mg | 2 |
Parts 1 and 2: Cmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Cmax was defined as the maximum observed plasma concentration. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | ng/mL (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 26.2 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 22.9 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 103 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 86.1 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 196 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 271 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 449 |
Parts 1 and 2: Cmax Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
Cmax was defined as the maximum observed plasma concentration. (NCT02393248)
Timeframe: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
| Intervention | ng/mL (Mean) |
|---|
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fasted | 215 |
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fed | 179 |
E0 Following Once Daily Dosing of Pemigatinib as Monotherapy in Parts 1 and 2
E0 was defined as the Baseline serum concentration of phosphate. (NCT02393248)
Timeframe: predose on Days 1 and 14 of Cycle 1; anytime during visit on Day 1 of Cycle 2 and all subsequent cycles
| Intervention | milligrams per deciliter (mg/dL) (Geometric Mean) |
|---|
| Parts 1 and 2: Intermittent or Continuous Pemigatinib | 3.66 |
Parts 1 and 2: Cmin Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
Cmin was defined as the minimum observed plasma concentration over the dose interval. (NCT02393248)
Timeframe: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
| Intervention | ng/mL (Mean) |
|---|
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fasted | 61.1 |
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fed | 65.7 |
Parts 1 and 2: t1/2 After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
t1/2 was defined as the apparent plasma terminal phase disposition half-life. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | hr (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 10.9 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 18.1 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 30.4 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 21.0 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 17.2 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 17.4 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 13.1 |
Parts 1 and 2: t1/2 Steady State Following Administration of Pemigatinib in the Fasted (Cycle 1 Day 14) and Fed (Cycle 2 Day 14) States
t1/2 was defined as the apparent plasma terminal phase disposition half-life. (NCT02393248)
Timeframe: Cycles 1 and 2: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Day 14
| Intervention | hr (Mean) |
|---|
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fasted | 19.2 |
| Part 2: Intermittent/Continuous Pemigatinib 13.5 mg QD, Fed | 23.8 |
Parts 1 and 2: Tmax After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Day 1
tmax was defined as the time to the maximum observed plasma concentration. (NCT02393248)
Timeframe: Part 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose post-dose on Cycle 1 Day 1. Part 2: predose on Cycle 1 Day 1
| Intervention | hours (hr) (Median) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 1 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 5.92 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 2.02 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 1.14 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 1.17 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 1.20 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 1.98 |
Parts 1 and 2: Vz/F After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Vz/F was defined as the apparent volume of distribution. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | Liters (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 156 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 334 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 260 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 301 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 246 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 274 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 180 |
Part 3: t1/2 of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
t1/2 was defined as the apparent plasma terminal phase disposition half-life. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | hr (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 15.3 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 17.0 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 10.6 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 14.7 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 15.3 |
Part 3: ORR
ORR was defined as the percentage of participants with a best overall response of CR or PR, per RECIST version 1.1, as determined by the investigator. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. (NCT02393248)
Timeframe: up to 203 days
| Intervention | percentage of participants (Number) |
|---|
| Part 3: Gem/Cis/Intermittent Pemigatinib 9 mg | 0.0 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 42.9 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 0.0 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 14.3 |
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 0.0 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 28.6 |
| Part 3: Pem/Continuous Pemigatinib 13.5 mg | 33.3 |
| Part 3: Ref/Continuous Pemigatinib 9 mg | 0.0 |
| Part 3: Ref/Continuous Pemigatinib 13.5 mg | 22.2 |
| Part 3: Ref/Continuous Pemigatinib 20 mg | 0.0 |
Part 3: Cmin of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Cmin was defined as the minimum observed plasma concentration over the dose interval. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | ng/mL (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 58.0 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 56.6 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 48.5 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 63.1 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 64.2 |
Part 3: Cmax of Pemigatinib as Part of Combination Therapy on Cycle 1 Day 14 (Steady State)
Cmax was defined as the maximum observed plasma concentration. (NCT02393248)
Timeframe: predose and 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | ng/mL (Mean) |
|---|
| Part 3: Pem/Intermittent Pemigatinib 9 mg | 166 |
| Part 3: Pem/Intermittent Pemigatinib 13.5 mg | 255 |
| Part 3: Gem/Cis/Intermittent Pemigatinib 13.5 mg | 214 |
| Part 3: Doc/Intermittent Pemigatinib 13.5 mg | 231 |
| Part 3: Tras/Intermittent Pemigatinib 13.5 mg | 404 |
Parts 1 and 2: Cmin After Once Daily Dosing of Pemigatinib as Monotherapy on Cycle 1 Days 8 and 14 (Steady State)
Cmin was defined as the minimum observed plasma concentration over the dose interval. (NCT02393248)
Timeframe: Part 1: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14. Part 2: predose on Cycle 1 Days 8 and 14; 0.5, 1, 2, 4, 6, and 8 hours post-dose on Cycle 1 Day 14
| Intervention | ng/mL (Mean) |
|---|
| Part 1: Intermittent Pemigatinib 1 mg QD | 3.24 |
| Part 1: Intermittent Pemigatinib 2 mg QD | 7.87 |
| Part 1: Intermittent Pemigatinib 4 mg QD | 23.9 |
| Part 1: Intermittent Pemigatinib 6 mg QD | 30.0 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 9 mg QD | 49.9 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 13.5 mg QD | 71.7 |
| Parts 1 and 2: Intermittent/Continuous Pemigatinib 20 mg QD | 104 |
Number of Participants With 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. (NCT02395172)
Timeframe: Time from date of randomization up to 1420 days
| Intervention | Participants (Count of Participants) |
|---|
| ADAs to Avelumab | NAbs to Avelumab |
|---|
| Avelumab | 58 | 14 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) by Severity
Treatment Emergent Adverse Events were graded as per National Cancer Institute Common Terminology Criteria for Adverse Experience version 4.03 (NCI-CTCAE v 4.03). Grade 3 refers to severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care and Activity of daily living (ADL), Grade 4 refers to Life-threatening consequences; where urgent intervention indicated, Grade 5 refers to the death related to adverse event. (NCT02395172)
Timeframe: Time from date of randomization up to 1420 days
| Intervention | Participants (Count of Participants) |
|---|
| Grade 3 or Higher | Grade 4 or Higher | Grade 5 |
|---|
| Avelumab | 209 | 87 | 63 |
,| Docetaxel | 247 | 122 | 51 |
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Visual Analogue Scale (VAS) at End of Treatment (EOT)
EQ-5D-5L was comprised of the following 5 participant-reported dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension had 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. The responses were used to derive overall score using a visual analog scale (VAS) that ranged from 0 to 100 millimeter (mm), where 0 was the worst health you can imagine and 100 was the best health you can imagine. (NCT02395172)
Timeframe: Baseline, End of treatment visit (up to Week 124)
| Intervention | millimeter (Mean) |
|---|
| Avelumab | -8.1 |
| Docetaxel | -7.0 |
Overall Survival (OS) Time in Full Analysis Set Population
The OS time was defined as the time from randomization to the date of 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. (NCT02395172)
Timeframe: Time from date of randomization up to 1420 days
| Intervention | months (Median) |
|---|
| Avelumab | 10.6 |
| Docetaxel | 9.9 |
Overall Survival (OS) Time in Programmed Death Ligand 1 (PD-L1) + Full Analysis Set Population (FAS)
The OS time was defined as the time from randomization to the date of 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. (NCT02395172)
Timeframe: Time from date of randomization up to 1420 days
| Intervention | months (Median) |
|---|
| Avelumab | 11.4 |
| Docetaxel | 10.6 |
Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in Full Analysis Set Population
Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. 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. (NCT02395172)
Timeframe: Time from date of randomization up to 907 days
| Intervention | percentage of participants (Number) |
|---|
| Avelumab | 14.9 |
| Docetaxel | 11.1 |
Percentage of Participants With Objective Response as Assessed by Independent Endpoint Review Committee (IERC) in PD-L1+ Full Analysis Set Population
Percentage of participants with objective response (CR plus PR) according to RECIST v1.1 was reported. 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. (NCT02395172)
Timeframe: Time from date of randomization up to 907 days
| Intervention | percentage of participants (Number) |
|---|
| Avelumab | 18.9 |
| Docetaxel | 11.7 |
Change From Baseline in European Quality of Life 5-dimensions (EQ-5D-5L) Health Outcome Questionnaire Through Composite Index Score at End of Treatment (EOT)
The EQ-5D-5L health outcome questionnaire was a measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L defined health in terms of mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The 5 items were combined to generate health profiles. These profiles were converted to a continuous single index score. The lowest possible score was -0.59 (unable to walk, unable to self-care, unable to do usual activities, extreme pain or discomfort, extreme anxiety or depression) and the highest was 1.00 (no problems in all 5 dimensions). (NCT02395172)
Timeframe: Baseline, End of treatment visit (up to Week 124)
| Intervention | units on a scale (Mean) |
|---|
| Avelumab | -0.1245 |
| Docetaxel | -0.0988 |
Progression-Free Survival (PFS) Time in Full Analysis Set Population
PFS was 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. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) 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. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02395172)
Timeframe: Time from date of randomization up to 907 days
| Intervention | months (Median) |
|---|
| Avelumab | 2.8 |
| Docetaxel | 4.2 |
Progression-Free Survival (PFS) Time in PD-L1+ Full Analysis Set Population
PFS was 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. PFS was assessed as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as adjudicated by independent endpoint review committee (IERC). PD was defined as at least a 20 percent (%) 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. PFS was measured using Kaplan-Meier (KM) estimates. (NCT02395172)
Timeframe: Time from date of randomization up to 907 days
| Intervention | months (Median) |
|---|
| Avelumab | 3.4 |
| Docetaxel | 4.1 |
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)
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. (NCT02395172)
Timeframe: Baseline, End of treatment visit (up to Week 124)
| Intervention | units on a scale (Mean) |
|---|
| Avelumab | -9.79 |
| Docetaxel | -9.44 |
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)
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, 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). (NCT02395172)
Timeframe: Baseline, End of treatment visit (up to Week 124)
| Intervention | units on a scale (Mean) |
|---|
| Dyspnea | Coughing | Hemoptysis | Sore Mouth | Dysphagia | Peripheral Neuropathy | Alopecia | Pain in Chest | Pain in Arm or Shoulder | Pain in Other Parts |
|---|
| Avelumab | 9.95 | -0.58 | 0.19 | 0.78 | 5.62 | 0.19 | -3.10 | 4.84 | 5.62 | 8.77 |
,| Docetaxel | 8.52 | -2.03 | -0.34 | 3.72 | 4.23 | 9.81 | 30.80 | 0.34 | 0.85 | 6.60 |
Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance: Baseline Score 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. The participants with missing worst post baseline score were also reported. ECOG performance status was reported in terms of number of participants with Baseline value vs. worst post-baseline value (i.e. highest score) combination. (NCT02395172)
Timeframe: Time from date of randomization up to 1420 days
| Intervention | Participants (Count of Participants) |
|---|
| Baseline score 0, worst post-baseline score 0 | Baseline score 0, worst post-baseline score 1 | Baseline score 0, worst post-baseline score 2 | Baseline score 0, worst post-baseline score 3 | Baseline score 0, worst post-baseline score 4 | Baseline score 0, worst post-baseline score 5 | Baseline score 0, worst post-baseline Missing | Baseline score 1, worst post-baseline score 0 | Baseline score 1, worst post-baseline score 1 | Baseline score 1, worst post-baseline score 2 | Baseline score 1, worst post-baseline score 3 | Baseline score 1, worst post-baseline score 4 | Baseline score 1, worst post-baseline score 5 | Baseline score 1, worst post-baseline Missing |
|---|
| Avelumab | 52 | 67 | 19 | 5 | 0 | 1 | 0 | 6 | 157 | 47 | 23 | 3 | 1 | 12 |
,| Docetaxel | 55 | 41 | 12 | 2 | 1 | 0 | 6 | 1 | 172 | 41 | 8 | 2 | 1 | 23 |
Primary Efficacy Outcome: Progression Free Survival (PFS)
Efficacy of vofatamab plus docetaxel, compared with docetaxel plus placebo, and vofatamab alone as measured by PFS; measured from randomization to first occurrence of disease progression (per RECIST v1.1) or death, whichever occurs first. A patient has had to receive at least one vofatamab dose. 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. (NCT02401542)
Timeframe: 3-4 years
| Intervention | Months (Mean) |
|---|
| Mut/Fus Phase 1 | 6.82 |
| Wild Type Phase 1 | 2.83 |
| Mut/Fus Phase 2 | 4.40 |
| Mut/Fus Phase 2 Monotherapy | 4.45 |
| Mut/Fus Phase 2b Monotherapy | 2.23 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Carboplatin + Paclitaxel Then Doxorubicin + Cyclophosphamide | 31 |
| Carboplatin + Docetaxel | 35 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Carboplatin + Paclitaxel Then Doxorubicin + Cyclophosphamide | 26 |
| Carboplatin + Docetaxel | 28 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Trastuzumab With AC-TH Regimen | 46 |
| Trastuzumab With TCH Regimen | 51 |
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.
| Intervention | Months (Median) |
|---|
| Trastuzumab With AC-TH Regimen | NA |
| Trastuzumab With TCH Regimen | NA |
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
| Intervention | Months (Median) |
|---|
| Trastuzumab With AC-TH Regimen | NA |
| Trastuzumab With TCH Regimen | NA |
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)
| Intervention | Percentage of LVEF (Mean) |
|---|
| Baseline | Cycle 5 | Cycle 9 | Cycle 13 | Cycle 17 | Cycle 21 | Study Completion Visit | 6 Month Follow Up | 12 Month Follow Up |
|---|
| Trastuzumab With AC-TH Regimen | 60.1 | -0.2 | -0.5 | -2.0 | -1.8 | -1.8 | -3.3 | -1.6 | -2.2 |
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)
| Intervention | Percentage of LVEF (Mean) |
|---|
| Baseline | Cycle 5 | Cycle 9 | Cycle 13 | Cycle 17 | Study Completion Visit | 6 Month Follow Up | 12 Month Follow Up |
|---|
| Trastuzumab With TCH Regimen | 62.1 | -0.4 | -1.0 | -1.0 | -1.1 | -0.7 | -0.3 | -0.4 |
Percentage of Participants With Disease Control Rate (DCR)
DCR is the percentage of participants with a best overall response of CR, PR, or Stable Disease (SD) as per Response using RECIST v1.1. Target lesions - CR: Disappearance of all lesions; any pathological lymph nodes must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. Progressive Disease (PD): At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study (the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Non target lesions - CR: Disappearance of all lesions and normalization of tumor marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s). (NCT02426125)
Timeframe: Randomization to Disease Progression (Up to 29.7 Months)
| Intervention | percentage of participants (Number) |
|---|
| Ramucirumab + Docetaxel | 65.4 |
| Placebo + Docetaxel | 55.1 |
Progression Free Survival (PFS)
PFS defined as time from first day of therapy to first evidence of disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause. Progressive Disease (PD) is at least 20% increase in sum of diameters of target lesions, with reference being the smallest sum on study and plus 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, then PFS time was censored at date of first dose, regardless of whether or not objectively determined disease progression or death has been observed for participant. If participant is not known to have died or have objective progression as of data inclusion cutoff date for analysis, PFS time was censored at last adequate tumor assessment date. (NCT02426125)
Timeframe: Randomization to Radiological Disease Progression or Death from Any Cause (Up to 18 Months)
| Intervention | Months (Median) |
|---|
| Ramucirumab + Docetaxel | 4.07 |
| Placebo + Docetaxel | 2.76 |
Percentage of Participants With an Objective Response Rate (ORR)
ORR is defined as the percentage of participants who achieve a best overall response of complete response (CR) + partial response (PR). ORR = CR + PR. CR is defined as disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 millimeter (mm). Tumor-marker results must have normalized. PR is at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Best overall response is classified based on the overall responses assessed by study investigators according to RECIST v1.1. (NCT02426125)
Timeframe: Randomization to Disease Progression (Up to 29.7 Months)
| Intervention | percentage of participants (Number) |
|---|
| Ramucirumab + Docetaxel | 25.9 |
| Placebo + Docetaxel | 13.9 |
Overall Survival (OS)
OS is the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data inclusion cutoff date for a particular analysis, OS was censored for that analysis at the last known alive date prior to the data inclusion cutoff date. (NCT02426125)
Timeframe: Randomization to Date of Death from Any Cause (Up to 31.1 Months)
| Intervention | Months (Median) |
|---|
| Ramucirumab + Docetaxel | 9.40 |
| Placebo + Docetaxel | 7.85 |
PK: Minimum Concentration (Cmin) of Ramucirumab
Cmin of Ramucirumab following administration every 3 weeks. (NCT02426125)
Timeframe: Day 1 of Cycle 2, 3, 5 and 9 (Predose and Postdose)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Cycle 2 | Cycle 3 | Cycle 5 | Cycle 9 |
|---|
| Ramucirumab + Docetaxel | 14.9 | 23.5 | 32.5 | 48.9 |
Number of Participants With Anti-Ramucirumab Antibodies
Number of participants with positive treatment emergent anti-ramucirumab antibodies was summarized by treatment group. (NCT02426125)
Timeframe: 29.7 Months
| Intervention | Participants (Count of Participants) |
|---|
| Ramucirumab + Docetaxel | 3 |
| Placebo + Docetaxel | 8 |
Duration of Response (DoR)
Objective response was achieved if they had a best overall response of CR or PR. Target lesions- CR: Disappearance of all lesions; any pathological lymph nodes have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of lesions vs the baseline sum. PD: At least a 20% increase in the sum of diameters of lesions vs the smallest sum on study(the sum must also demonstrate an absolute increase of at least 5 mm); or the appearance of new lesion(s). Non target lesions - CR: Disappearance of all lesions and normalization of tumour marker levels; all lymph nodes must be non-pathological in size. Non-CR/Non-PD: Persistence of lesion(s) and/or maintenance of abnormal tumor marker levels. PD: Unequivocal progression of existing lesions or the appearance of new lesion(s). If a participant was not known to have died or have radiographically documented PD as of the data inclusion cutoff date, DOR was censored at the date of the last adequate tumor assessment. (NCT02426125)
Timeframe: Date of Complete Response (CR) or Partial Response (PR) to Date of Objective Disease Progression or Death Due to Any Cause (Up to 28.4 Months)
| Intervention | Months (Median) |
|---|
| Ramucirumab + Docetaxel | 5.32 |
| Placebo + Docetaxel | 4.17 |
Time to Deterioration in Quality of Life (QoL) on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Global Health Status/ QoL Scale
Time to sustained deterioration was defined as time from randomization to first worsening in QoL with no subsequent non-worsened assessment. Worsening in global health status/QoL was defined as a decrease of ≥10 points on a 100-point scale. If a participant did not report worsening, time to sustained deterioration was censored at date of last non-worsened assessment. Scores for global health status/QoL range from 0 to 100 with; higher scores representing better QoL. (NCT02426125)
Timeframe: Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
| Intervention | Months (Median) |
|---|
| Ramucirumab + Docetaxel | 6.87 |
| Placebo + Docetaxel | 4.60 |
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Ramucirumab
Cmax of Ramucirumab at the end of ramucirumab infusion. (NCT02426125)
Timeframe: Cycle 1 and Cycle 9, Day 1: Predose, Postdose
| Intervention | microgram/milliliter (μg/mL) (Geometric Mean) |
|---|
| Cycle 1 | Cycle 9 |
|---|
| Ramucirumab + Docetaxel | 199 | 265 |
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Visual Analogue Scale (VAS)
The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. A unique EQ-5D health state is defined by combining 1 level from each of the 5 dimensions. Participants indicated their current health status by marking on a VAS ranging from 100 (best imaginable health state) to 0 (worst imaginable health state). (NCT02426125)
Timeframe: Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
| Intervention | millimeter (mm) (Mean) |
|---|
| Ramucirumab + Docetaxel | -7.87 |
| Placebo + Docetaxel | -10.91 |
Change From Baseline on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) Index Score
The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Participants completed the 5-level (no problem, slight problem, moderate problem, severe problem, and inability or extreme problem), 5-dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) questionnaire concerning their current health state. A unique EQ-5D health state is defined by combining 1 level from each of the 5 dimensions. Scores range from 0 (death) to 1 (perfect health), but scores <0 are possible based on the algorithm. (NCT02426125)
Timeframe: Randomization, 30 Days After Treatment Discontinuation (Up to 18 Months)
| Intervention | units on a scale (Mean) |
|---|
| Ramucirumab + Docetaxel | -0.10 |
| Placebo + Docetaxel | -0.19 |
Overall Number of Participants With Non-Serious Adverse Events by Event Outcome
The number of participants with non-serious adverse events was counted by the event outcome in the four following categories: resolved with no sequelae, resolved with sequelae, unresolved, or death. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events with the same outcome were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Resolved with No Sequelae | Resolved with Sequelae | Unresolved | Death |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 42 | 12 | 27 | 2 |
Overall Number of Participants With Non-Serious Adverse Events by Treatment Emergence (TEAE Versus Non-TEAE)
The number of participants with non-serious adverse events was counted according to whether the event was considered a treatment emergent adverse event (TEAE), which is defined as an adverse event that emerges during treatment, having been absent pretreatment, or worsens relative to the pretreatment state. Participants with multiple occurrences of non-serious adverse events were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Non-TEAEs |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 47 | 3 |
Overall Number of Participants With Non-Serious Adverse Events by Action Taken With Pertuzumab
The number of participants with non-serious adverse events was counted by the type of action taken with pertuzumab in response to the adverse event in the three following categories: no action taken, infusion slow down, infusion interrupted, and appropriate medical therapies administered. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| No Action Taken | Infusion Slow Down | Infusion Interrupted | Appropriate Medical Therapies Administered |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 47 | 0 | 0 | 0 |
Overall Number of Participants by the Number of Serious Adverse Events Reported Per Participant
The number of participants with serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 serious adverse event categories) were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| ≥1 Serious Adverse Event | 1 Serious Adverse Event | >1 Serious Adverse Events | 0 Serious Adverse Events |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 31 | 17 | 14 | 21 |
Overall Number of Participants With Non-Serious Adverse Events by Severity, According to NCI-CTCAE v4.03
"The number of participants with non-serious adverse events was counted by the severity level of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms severe and serious are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of non-serious adverse events of the same severity were only counted once per severity category." (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 38 | 34 | 12 | 1 | 0 |
Number of Participants With Congestive Heart Failure
(NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 0 |
Number of Participants With Hematological Abnormalities Reported as Serious Adverse Events
The number of participants with hematological laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 2 |
Number of Participants With Serum Chemistry Abnormalities Reported as Serious Adverse Events
The number of participants with serum chemistry laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 0 |
Number of Participants With Coagulation Abnormalities Reported as Serious Adverse Events
The number of participants with coagulation laboratory abnormalities reported as serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of the same serious adverse event were only counted once per preferred term. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 1 |
Number of Participants With Adverse Events Leading to Treatment Discontinuation
The number of participants with any adverse event (serious or non-serious) that led to treatment discontinuation during the study was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one adverse event that led to treatment discontinuation may have been reported per participant. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Any AEs Leading to Treatment Discontinuation | Disease progression | Ejection fraction decreased | Headache | Anaemia | Death | Diarrhoea | Dyspnoea | Febrile neutropenia | Infusion related reaction | Sepsis | Septic shock | Shock | Stevens-Johnson syndrome |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 16 | 5 | 3 | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) Over Time
Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF of ≥50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. (NCT02445586)
Timeframe: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)
| Intervention | percentage points of LVEF (Mean) |
|---|
| Baseline (BL) - Value at Visit | Change from BL at Cycle 3 | Change from BL at Cycle 6 | Change from BL at Cycle 9 | Change from BL at Cycle 12 | Change from BL at Cycle 15 | Change from BL at Cycle 18 | Change from BL at Cycle 21 | Change from BL at Cycle 24 | Change from BL at Cycle 27 | Change from BL at Cycle 30 | Change from BL at Cycle 33 | Change from BL at Cycle 36 | Change from BL at Cycle 39 | Change from BL at Cycle 42 | Change from BL at Cycle 45 | Change from BL at Cycle 48 | Change from BL at Cycle 51 | Change from BL at Safety Follow-Up | Change from BL at 3 Month Follow-Up | Change from BL at 6 Month Follow-Up | Change from BL at 9 Month Follow-Up | Change from BL at 12 Month Follow-Up | Change from BL at 15 Month Follow-Up | Change from BL at 18 Month Follow-Up | Change from BL at 21 Month Follow-Up | Change from BL at 24 Month Follow-Up |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 59.6 | -0.7 | -0.8 | -0.2 | 0.2 | -0.8 | -1.3 | -1.8 | -0.7 | 0.0 | -1.3 | -0.5 | 0.0 | -1.3 | 1.0 | 0.0 | -2.0 | -18.0 | -4.3 | -2.1 | -1.8 | -3.4 | -2.3 | -4.7 | -10.0 | -5.0 | -5.0 |
Number of Participants by Best Overall Response
The best overall response was defined as the best response, out of all the documented responses over the course of the entire study period, using RECIST v1.1. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator. (NCT02445586)
Timeframe: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response (CR) | Partial Response (PR) | Progressive Disease (PD) | Stable Disease (SD) | Unable to Assess |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 0 | 43 | 1 | 6 | 2 |
Number of Participants Who Died Due to a Serious Adverse Event by Cause of Death
The number of participants who died due to a serious adverse event was counted by the cause of death. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Disease progression | Sepsis and disease progression | Dyspnoea | Septic shock | Shock | Unknown cause |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 10 | 1 | 1 | 1 | 1 | 1 |
Number of Participants Who Died or Were Censored for Overall Survival Analysis
Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method. (NCT02445586)
Timeframe: From Baseline up to death from any cause (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Death | Censored |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 15 | 37 |
Overall Number of Participants by the Number of Non-Serious Adverse Events Reported Per Participant
The number of participants with non-serious adverse events was counted in the four following categories for number of events reported per participant: greater than or equal to (≥) 1, 1, greater than (>) 1, or 0 non-serious adverse events. Participants with multiple occurrences of events (the ≥1 and >1 non-serious adverse event categories) were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| ≥1 Non-Serious Adverse Event | 1 Non-Serious Adverse Event | >1 Non-Serious Adverse Events | 0 Non-Serious Adverse Events |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 47 | 11 | 36 | 5 |
Number of Participants With Serum Chemistry Abnormalities Reported as Non-Serious Adverse Events
The number of participants with serum chemistry laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Hypomagnesaemia | Hypokalaemia | Hypoalbuminaemia | Hypophosphataemia | Hyperglycaemia | Hyperuricaemia | Liver function test abnormal |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 4 | 2 | 1 | 1 | 1 | 1 | 1 |
Overall Number of Participants With Non-Serious Adverse Events by Chemotherapy Adjustment With Docetaxel and/or Trastuzumab
The number of participants with non-serious adverse events was counted by the type of action taken with docetaxel and/or trastuzumab in response to the adverse event in the three following categories: no adjustment, dosage modified/interrupted, and discontinued. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of non-serious adverse events that required the same action to be taken with the study drug were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| No Adjustment | Dosage Modified / Interrupted | Discontinued |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 45 | 9 | 7 |
Number of Participants With Hematological Abnormalities Reported as Non-Serious Adverse Events
The number of participants with hematological laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Anaemia | Leukopenia | Neutropenia | Febrile neutropenia | Iron deficiency | Thrombocytopenia |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 8 | 4 | 2 | 1 | 1 | 1 |
Number of Participants With Disease Progression or Death or Who Were Censored for Progression-Free Survival Analysis
Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed or died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method. (NCT02445586)
Timeframe: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Disease Progression or Death | Censored |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 32 | 20 |
Number of Participants With Coagulation Abnormalities Reported as Non-Serious Adverse Events
The number of participants with coagulation laboratory abnormalities reported as non-serious adverse events was counted. Adverse events (AEs) were encoded according to the Medical Dictionary for Regulatory Activities (MedDRA) version 21.1. More than one non-serious adverse event may have been reported per participant. Participants with multiple occurrences of the same non-serious adverse event were only counted once per preferred term. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Thrombocytopenia | Anal haemorrhage | Haemorrhoidal haemorrhage | Rectal haemorrhage | Upper gastrointestinal haemorrhage | Vaginal haemorrhage | Thrombophlebitis |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
Number of Participants by Left Ventricular Ejection Fraction (LVEF) Findings Over Time
Left ventricular ejection fraction (LVEF) assessments were performed within 42 days of enrollment and every three treatment cycles by either echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan; ECHO was the preferred method. In order to be eligible for this study, an LVEF greater than or equal to (≥)50% was required at screening. The same method of LVEF assessment for each participant must have been used throughout the study, and to the extent possible, have been obtained at the same institution. The following are definitions for the three categories of LVEF findings: 'Normal' was defined as LVEF ≥45%; 'Abnormal but not clinically significant' was defined as LVEF <45% but not clinically significant in the investigator's judgment; 'Abnormal and clinically significant' was defined as LVEF <45% and clinically significant in the investigator's judgment. (NCT02445586)
Timeframe: Baseline, every 3 cycles (1 cycle is 21 days) until treatment discontinuation, at Safety Follow-Up (28 days after last dose of study drug) and every 3 months thereafter until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Baseline72586706 | Cycle 372586706 | Cycle 672586706 | Cycle 972586706 | Cycle 1272586706 | Cycle 1572586706 | Cycle 1872586706 | Cycle 2172586706 | Cycle 2472586706 | Cycle 2772586706 | Cycle 3072586706 | Cycle 3372586706 | Cycle 3672586706 | Cycle 3972586706 | Cycle 4272586706 | Cycle 4572586706 | Cycle 4872586706 | Cycle 5172586706 | Safety Follow-Up72586706 | 3 Month Follow-Up72586706 | 6 Month Follow-Up72586706 | 9 Month Follow-Up72586706 | 12 Month Follow-Up72586706 | 15 Month Follow-Up72586706 | 18 Month Follow-Up72586706 | 21 Month Follow-Up72586706 | 24 Month Follow-Up72586706 |
|---|
| Normal | Abnormal But Not Clinically Significant | Abnormal and Clinically Significant |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 50 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 2 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 0 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 48 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 3 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 37 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 24 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 17 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 16 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 11 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 10 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 1 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 8 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 5 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 18 |
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 13 |
Probability of Participants Remaining Event-Free in Progression-Free Survival From 2 to 32 Months
Progression-free survival (PFS) was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator using RECIST v1.1, or death from any cause, whichever occurred first. Participants who had not progressed, died or were lost to follow up at the time of the analysis were censored on the last visit at which assessment for progression was done (2 years after the last participant was enrolled). PFS was analyzed by the Kaplan-Meier method. (NCT02445586)
Timeframe: Months 2, 3, 5, 6, 7, 8, 9, 11, 13, 15, 16, 17, 18, 19, 23, 24, 25, 27, 29, and 32
| Intervention | Percent probability of PFS (Number) |
|---|
| At 2 Months | At 3 Months | At 5 Months | At 6 Months | At 7 Months | At 8 Months | At 9 Months | At 11 Months | At 13 Months | At 15 Months | At 16 Months | At 17 Months | At 18 Months | At 19 Months | At 23 Months | At 24 Months | At 25 Months | At 27 Months | At 29 Months | At 32 Months |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 98.08 | 96.15 | 90.27 | 88.30 | 82.42 | 78.49 | 74.57 | 68.52 | 64.49 | 60.33 | 58.10 | 55.86 | 53.63 | 51.30 | 48.96 | 46.63 | 41.72 | 36.16 | 32.87 | 29.59 |
Probability of Participants Remaining Alive in Overall Survival From 3 to 34 Months
Overall survival was defined as the time from enrollment to the the date of death from any cause. Participants who were alive at the time of the analysis, dropped out of the study, or lost to follow-up were censored at the date of the last follow-up assessment. Participants without follow-up assessment were censored at the day of last study medication, and participants with no post-baseline information were censored at baseline. Overall survival was analyzed by the Kaplan-Meier method. (NCT02445586)
Timeframe: Months 3, 9, 13, 14, 15, 18, 19, 20, 24, 25, 27, 32, 33, and 34
| Intervention | Percent probability of OS (Number) |
|---|
| At 3 Months | At 9 Months | At 13 Months | At 14 Months | At 15 Months | At 18 Months | At 19 Months | At 20 Months | At 24 Months | At 25 Months | At 27 Months | At 32 Months | At 33 Months | At 34 Months |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 96.15 | 88.30 | 88.30 | 88.30 | 88.30 | 83.66 | 83.66 | 83.66 | 81.12 | 81.12 | 68.14 | 68.14 | 64.36 | 64.36 |
Overall Response Rate
The overall response rate (ORR) was defined as the percentage of participants with best overall response of Complete Response (CR) or Partial Response (PR), confirmed by repeat assessment no less than 4 weeks after the response criteria were first met, using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Participants who either had not achieved CR or PR or were without a post-baseline tumor assessment were to be considered non-responders. All measurable and non-measurable lesions were documented at screening and re-assessed at each subsequent tumor evaluation. Response was assessed by the investigator on the basis of physical examinations, computed tomography (CT) scans, and magnetic resonance imaging (MRI). The same radiographic procedure was used throughout the study, and assessments were preferably performed by the same evaluator. The 95% confidence intervals were calculated using Clopper-Pearson methodology. (NCT02445586)
Timeframe: From Baseline up to disease progression or death (assessed at every 9 weeks, up to approximately 3 years)
| Intervention | percentage of participants (Number) |
|---|
| Responders (ORR) | Non-Responders |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 82.7 | 17.3 |
Overall Number of Participants With Serious Adverse Events by Severity (Initial and Most Extreme), According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.03 (NCI CTCAE v4.03)
"The number of participants with serious adverse events was counted by the initial and most extreme levels of severity of the adverse event, assessed as Grades 1-5 according to NCI CTCAE v4.03. Any adverse event not specifically listed in NCI CTCAE v4.03 was assessed according to the following grades of severity: Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life-threatening or urgent intervention indicated; and Grade 5 is death related to adverse event. The terms severe and serious are not synonymous. Severity refers to the intensity of an adverse event. The seriousness of an adverse event is based on whether it meets any of the criteria set out in the protocol's definition of a serious adverse event. Severity and seriousness were independently assessed for each adverse event. Participants with multiple occurrences of serious adverse events of the same severity were only counted once per severity category." (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Initial Severity - Grade 1 | Initial Severity - Grade 2 | Initial Severity - Grade 3 | Initial Severity - Grade 4 | Initial Severity - Grade 5 | Most Extreme Severity - Grade 1 | Most Extreme Severity - Grade 2 | Most Extreme Severity - Grade 3 | Most Extreme Severity - Grade 4 | Most Extreme Severity - Grade 5 |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 1 | 4 | 15 | 7 | 14 | 1 | 3 | 16 | 7 | 15 |
Overall Number of Participants With Serious Adverse Events by Event Outcome
The number of participants with serious adverse events was counted by the event outcome in the six following categories: fatal, recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not recovered/not resolved, or unknown. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events with the same outcome were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Fatal | Recovered / Resolved | Recovered / Resolved with Sequelae | Recovering / Resolving | Not Recovered / Not Resolved | Unknown |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 15 | 18 | 1 | 3 | 2 | 0 |
Overall Number of Participants With Serious Adverse Events by Action Taken With Study Drug
The number of participants with serious adverse events was counted by the type of action taken with the study drug (docetaxel, pertuzumab, and trastuzumab) in response to the adverse event in the three following categories: infusion reduced, temporarily interrupted, or permanently discontinued. More than one serious adverse event may have been reported per participant. Participants with multiple occurrences of serious adverse events that required the same action to be taken with the study drug were only counted once per category. (NCT02445586)
Timeframe: From Baseline until end of study (up to approximately 3 years)
| Intervention | Participants (Count of Participants) |
|---|
| Infusion of Docetaxel Reduced | Infusion of Docetaxel Temporarily Interrupted | Infusion of Docetaxel Permanently Discontinued | Infusion of Pertuzumab Reduced | Infusion of Pertuzumab Temporarily Interrupted | Infusion of Pertuzumab Permanently Discontinued | Infusion of Trastuzumab Reduced | Infusion of Trastuzumab Temporarily Interrupted | Infusion of Trastuzumab Permanently Discontinued |
|---|
| Pertuzumab in Combination With Trastuzumab and Docetaxel | 0 | 1 | 1 | 0 | 3 | 4 | 0 | 3 | 5 |
Pharmacokinetics (PK): Clearance of Abemaciclib
Pharmacokinetics (PK): Clearance of Abemaciclib (NCT02450539)
Timeframe: Cycle (C) 1 Day (D) 1: Pre-dose; C1D8: 4 and 7 hr Post-dose; C2D1: Pre-dose and 3 hr Post-dose; C3 and C4 D1:Pre-dose
| Intervention | Liters/hour (L/h) (Geometric Mean) |
|---|
| Abemaciclib | 21.3 |
Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire EQ VAS Overall Self-rated Health Score
The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Overall self-rated health was measured with a vertical 20 cm visual analog scale (VAS) anchored at 0 (worst health) and ranged through 100 (best health). Between-group differences in regression-predicted change from baseline score were estimated for VAS scores. MMRM models included independent variables treatment, visit, treatment*visit, and baseline score. Group-level negative change from baseline indicated group improvement. (NCT02450539)
Timeframe: Baseline to Measured Progressive Disease (Up To 6 Months)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Abemaciclib | -5.49 |
| Docetaxel | -2.36 |
Change From Baseline in EuroQol 5-Dimensional 5-Level (EQ-5D-5L) Questionnaire Index Value
There are 5 response levels on a good-to-bad continuum of 1-5 corresponding to none, slight, moderate, severe, and extreme/unable to.The EuroQol-developed crosswalk method was used to convert the EQ-5D-5L,using UK weights,health dimensions(mobility,self-care,usual activities,pain/discomfort, and anxiety/depression) into a single index value;the dimensions are not separately scored.The index is marked missing when ≥1 dimensions are missing.The index scores for the response patterns were anchored on full health to dead with negative values assigned to response patterns/health states considered worse than death.The best pattern is assigned the index value of 1.0; the worst pattern is assigned an index value of -0.594. Between-group differences in regression-predicted change from baseline score were estimated for the index .MMRM models included independent variables treatment, visit, treatment*visit, and baseline score.Group-level negative change from baseline indicated group improvement. (NCT02450539)
Timeframe: Baseline to Measured Progressive Disease (Up To 6 Months)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Abemaciclib | -0.05 |
| Docetaxel | -0.01 |
Percentage of Participants Who Exhibit Stable Disease (SD) or Confirmed Response (CR) or Partial Response (PR): Disease Control Rate (DCR)
DCR is the percentage of randomized participants who achieved a complete response, partial response or stable disease using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Complete response (CR) is defined as the disappearance of all target and non-target lesions, and no appearance of new lesions. Partial response (PR) is defined as at least a 30% decrease in the sum of longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions. Stable disease 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. (NCT02450539)
Timeframe: Baseline through Measured Progressive Disease or Death Due to Any Cause (Up To 6 Months)
| Intervention | percentage participants (Number) |
|---|
| Abemaciclib | 50.9 |
| Docetaxel | 64.2 |
Percentage of Participants With Complete Response (CR) or Partial Response (PR) (Overall Response Rate [ORR])
Overall response was defined as the percentage of randomized participants achieving a best overall response (BoR) of complete response (CR) or partial response (PR) using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Participants with unevaluable or unknown response status are considered nonresponders. Complete response (CR) is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. Partial response (PR) is 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 non-target lesions and no appearance of new lesions. (NCT02450539)
Timeframe: Baseline to Objective Progression (Up To 6 Months)
| Intervention | percentage participants (Number) |
|---|
| Abemaciclib | 2.8 |
| Docetaxel | 20.8 |
Change From Baseline in MD Anderson Symptom Inventory-Lung Cancer (MDASI-LC) Scores
MDASI-LC included 33 items:6 interference and 27 symptom(3 lung-cancer (LC),8 brain tumor (BT),and 3 study-specific(headache,diarrhea, and rash).Analyzed endpoints were 9 constructs:3 single-items (headache,diarrhea,and rash) and 6 composites(interference+core,LC,core+LC,BT, and core+LC worst 5 baseline).Data for all 9 constructs were collected by an 11-point numeric rating scale anchored at 0(not present or does not interfere) and 10(as bad as you can imagine or interfered completely).The measurement range was 10 (maximum score-minimum score). Between-group difference in regression-predicted change from baseline were estimated for each specified construct. MMRM models included independent variables treatment,visit, treatment*visit,and baseline score. Group-level negative change from baseline indicated group improvement. (NCT02450539)
Timeframe: Baseline through End of Study (Up To 6 Months)
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Headache | Diarrhea | Mean core symptom severity | Mean interference | Mean lung cancer symptom severity | Mean core plus lung cancer symptom severity | Mean brain tumor symptom severity | Mean core plus lung worst 5 symptoms severity | Rash |
|---|
| Abemaciclib | 0.19 | 1.01 | 0.53 | 0.50 | 0.20 | 0.47 | 0.19 | -0.25 | 0.28 |
,| Docetaxel | 0.01 | 0.15 | 0.00 | 0.18 | -0.19 | -0.04 | 0.13 | -0.94 | 0.18 |
Progression Free Survival (PFS)
PFS was defined as time from the date of randomization to the date of investigator-determined disease progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) or death from any cause. Progressive disease (PD) was defined as at least a 20% increase in the sum of the longest diameters (LD) of target lesions, with reference the smallest sum on study and an absolute increase of at least 5mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant was not known to have died or have objective progression, PFS time will be censored at the day of their last radiographic tumor assessment (if available) or date of randomization if no post baseline radiographic assessment is available. (NCT02450539)
Timeframe: Baseline to Objective Progression or Death from Any Cause ( Up To 6 Months)
| Intervention | months (Median) |
|---|
| Abemaciclib | 2.53 |
| Docetaxel | 4.21 |
PK: Volume of Distribution of Abemaciclib
PK: Volume of Distribution of Abemaciclib (NCT02450539)
Timeframe: Cycle (C) 1 Day (D) 1: Pre-dose; C1D8: 4 and 7 hr Post-dose; C2D1: Pre-dose and 3 hr Post-dose; C3 and C4 D1:Pre-dose
| Intervention | Liters (L) (Geometric Mean) |
|---|
| Abemaciclib | 769 |
Overall Survival (OS)
OS was defined as the time from randomization to the date of death due to any cause. For each participant who is not known to have died as the data inclusion cutoff date for overall survival analysis, OS time was censored on the last date the participant is known to be alive. (NCT02450539)
Timeframe: Baseline to Date of Death from Any Cause (Up To 28 Months)
| Intervention | Months (Median) |
|---|
| Abemaciclib | 7 |
| Docetaxel | 12.39 |
Adverse Events as Measured by Number of Events Experienced by All Participants
(NCT02469116)
Timeframe: 30 days after completion of treatment (approximately 22 weeks)
| Intervention | events (Number) |
|---|
| Low white blood cell count | Low absolute neutrophil count | Low platelet count | Low hemoglobin | Allergy/immunology | Cardiovascular | Coagulation | Constitutional symptoms | Dermatology | Endocrine | Gastrointestinal | Genitourinary/renal | Hemorrhage | Infection/febrile neutropenia | Lymphatics | Metabolic/laboratory | Musculoskeletal | Neurologic | Ocular/visual | Pain | Pulmonary |
|---|
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | 25 | 21 | 47 | 78 | 3 | 4 | 1 | 42 | 64 | 56 | 43 | 1 | 2 | 9 | 2 | 74 | 6 | 30 | 2 | 27 | 2 |
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)
| Intervention | participants (Number) |
|---|
| Complete response | Partial response | Stable disease | Progressive disease |
|---|
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | 16 | 1 | 0 | 1 |
Incidence of Grade 3-4 Neutropenia as Measured by CTCAE Version 3
(NCT02469116)
Timeframe: Through 30 days after completion of treatment (approximately 22 weeks)
| Intervention | participants (Number) |
|---|
| Grade 3 neutropenia | Grade 4 neutropenia |
|---|
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | 4 | 0 |
Number of Participants Who Reported Grade 3 or Higher Adverse Events
The number of patients who reported grade 3 or higher Adverse Events according to Common Terminology Criteria for Adverse Events version 4.0. (NCT02485834)
Timeframe: Up to 30 days after completion of protocol treatment
| Intervention | Participants (Count of Participants) |
|---|
| Randomized Patients | 3 |
Number of Patients Achieved R0 Resection During Surgery
The number of patients achieved R0 resection during surgery (NCT02485834)
Timeframe: At time of surgery
| Intervention | Participants (Count of Participants) |
|---|
| Randomized Patients | 3 |
Overall Survival
Overall survival is defined as the time from date of randomization to death due to any cause. (NCT02485834)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| Randomized Patients | NA |
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), 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. The median and 95% confidence intervals are estimated using the Kaplan-Meier estimator. (NCT02485834)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| Randomized Patients | NA |
Number of Patients Had Pathologic Complete Response
The number of patients had pathologic complete response (pCR). (pCR is defined as no gross or microscopic tumor identified with the surgical specimen. All lymph nodes should be free of tumor to document a PCR. If no gross tumor is visible, section around the area of inflammation (nodularity) should be made every 2-3 cm and specimens examined.) (NCT02485834)
Timeframe: Up to 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Randomized Patients | 4 |
CL for Docetaxel Alone and in Combination With Pertuzumab
Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per hour per meter squared (mL/h/m^2). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. (NCT02490475)
Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
| Intervention | mL/h/m^2 (Mean) |
|---|
| Cycle 1 (n=6,0,6,0,5,0) | Cycle 2 (n=0,6,0,6,0,4) |
|---|
| Docetaxel 100 + Pertuzumab 420 | NA | 22976 |
,| Docetaxel 100 Alone | 18913 | NA |
,| Docetaxel 60 + Pertuzumab 1050 | NA | 35813 |
,| Docetaxel 60 Alone | 33128 | NA |
,| Docetaxel 75 + Pertuzumab 420 | NA | 23747 |
,| Docetaxel 75 Alone | 22013 | NA |
Vss for Docetaxel Alone and in Combination With Pertuzumab
The volume of distribution at steady state (Vss), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. (NCT02490475)
Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
| Intervention | mL/m^2 (Mean) |
|---|
| Cycle 1 (n=6,0,6,0,5,0) | Cycle 2 (n=0,6,0,6,0,4) |
|---|
| Docetaxel 100 + Pertuzumab 420 | NA | 428863 |
,| Docetaxel 100 Alone | 254233 | NA |
,| Docetaxel 60 + Pertuzumab 1050 | NA | 1023569 |
,| Docetaxel 60 Alone | 786981 | NA |
,| Docetaxel 75 + Pertuzumab 420 | NA | 566759 |
,| Docetaxel 75 Alone | 410174 | NA |
Volume of Distribution (Vz) at Steady State of Pertuzumab in Combination With Docetaxel
The volume of distribution at steady state (Vz), also known as apparent volume of distribution, is a pharmacological, theoretical volume that the total amount of administered drug would have to occupy (if it were uniformly distributed), to provide the same concentration as it currently is in blood plasma. (NCT02490475)
Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
| Intervention | mL (Mean) |
|---|
| Cycle 1 (n=8,11,0) | Cycle 2 (n=7,0,10) |
|---|
| Pertuzumab 1050 | 5214 | 4672 |
,| Pertuzumab 420 | NA | 4233 |
,| Pertuzumab 840 | 5355 | NA |
Tmax for Docetaxel Alone and in Combination With Pertuzumab
"Tmax is defined as the time after administration of a drug when the maximum plasma concentration is reached; Data for docetaxel alone arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. When the rate of absorption equals the rate of elimination. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1." (NCT02490475)
Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
| Intervention | days (Median) |
|---|
| Cycle 1 (n=6,0,6,0,5,0) | Cycle 2 (n=0,6,0,6,0,4) |
|---|
| Docetaxel 100 + Pertuzumab 420 | NA | 0.70 |
,| Docetaxel 100 Alone | 0.90 | NA |
,| Docetaxel 60 + Pertuzumab 1050 | NA | 0.90 |
,| Docetaxel 60 Alone | 0.50 | NA |
,| Docetaxel 75 + Pertuzumab 420 | NA | 0.90 |
,| Docetaxel 75 Alone | 0.50 | NA |
t1/2 for Docetaxel Alone and in Combination With Pertuzumab
"The biological half-life or terminal half-life of docetaxel is the time in hours it takes for it to lose half of its pharmacologic activity. Data for docetaxel alone arms were analyzed for the timepoints on Day 1 prior to the administration of pertuzumab. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1." (NCT02490475)
Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
| Intervention | days (Median) |
|---|
| Cycle 1 (n=6,0,6,0,5,0) | Cycle 2(n=0,6,0,6,0,4) |
|---|
| Docetaxel 100 + Pertuzumab 420 | NA | 11.8 |
,| Docetaxel 100 Alone | 8.92 | NA |
,| Docetaxel 60 + Pertuzumab 1050 | NA | 19.7 |
,| Docetaxel 60 Alone | 17.7 | NA |
,| Docetaxel 75 Alone | 12.0 | NA |
,| Docetaxel 75+ Pertuzumab 420 | NA | 13.8 |
Plasma Decay Half Life (t1/2) for Pertuzumab in Combination With Docetaxel
The biological half-life or terminal half-life of pertuzumab is the time in days it takes for it to lose half of its pharmacologic activity. (NCT02490475)
Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
| Intervention | days (Median) |
|---|
| Cycle 1 (n=8,11,0) | Cycle 2 (n=7,0,10) |
|---|
| Pertuzumab 1050 | 12.65 | 19.02 |
,| Pertuzumab 420 | NA | 18.46 |
,| Pertuzumab 840 | 11.65 | NA |
Percentage of Participants With Decrease in Left Ventricular Ejection Fraction (LVEF) by Category of Decrease and Timepoint
Ejection fraction (EF) is the fraction of outbound blood pumped from the heart with each heartbeat. It is commonly measured by echocardiogram and serves as a general measure of a person's cardiac function. Changes in LVEF were assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 criteria. The decrease in LVEF has been categorized as follows: A) Increase, no change, decrease from baseline less than (<) 10%; B) Absolute value <50% and decrease from baseline greater than or equal to (≥) 10%; C) Absolute value <50% and decrease from baseline≥15% ; D) Other. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. (NCT02490475)
Timeframe: Baseline, Weeks 7(Cycle 2), 13 (Cycle 4) and Final Visit Up to Week 22
| Intervention | percentage of participants (Number) |
|---|
| Cycle 2: A (n=6,1,6,4) | Cycle 2: B (n=6,1,6,4) | Cycle 2: C (n=6,1,6,4) | Cycle 2: D (n=6,1,6,4) | Cycle 4: A (n=5,1,4,3) | Cycle 4: B (n=5,1,4,3) | Cycle 4: C (n=5,1,4,3) | Cycle 4: D (n=5,1,4,3) | Final Visit: A (n=3,1,5,2) | Final Visit: B (n=3,1,5,2) | Final Visit: C (n=3,1,5,2) | Final Visit: D (n=3,1,5,2) |
|---|
| Docetaxel 100 + Pertuzumab 420 | 100.0 | 0.0 | 0.0 | 0.0 | 100.0 | 0.0 | 0.0 | 0.0 | 100.0 | 0.0 | 0.0 | 0.0 |
,| Docetaxel 60 Plus (+) Pertuzumab 1050 | 83.3 | 0.0 | 0.0 | 16.7 | 100.0 | 0.0 | 0.0 | 0.0 | 66.7 | 0.0 | 0.0 | 33.3 |
,| Docetaxel 75 + Pertuzumab 1050 | 100.0 | 0.0 | 0.0 | 0.0 | 100.0 | 0.0 | 0.0 | 0.0 | 100.0 | 0.0 | 0.0 | 0.0 |
,| Docetaxel 75 + Pertuzumab 420 | 100.0 | 0.0 | 0.0 | 0.0 | 75.0 | 25.0 | 0.0 | 0.0 | 80.0 | 0.0 | 0.0 | 20.0 |
Percentage of Participants by Best Overall Response Using Response Evaluation Criteria in Solid Tumors (RECIST) Criteria
Best Overall response was evaluated as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). CR: complete disappearance of all target lesions. PR: at least a 30 percent (%) decrease in the sum of the longest diameters. SD: neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum of the longest diameters since the treatment started. PD: 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 of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. If participants withdrew due to insufficient therapeutic response or death and had no tumor measurements at the final visit, they were counted under progressive disease for final visit. (NCT02490475)
Timeframe: Weeks 7 (Cycle 2),13 (Cycle 4) and Final Visit Up to 22 weeks
| Intervention | percentage of participants (Number) |
|---|
| Cycle 2: CR (n=6,1,6,4) | Cycle 2:PR (n=6,1,6,4) | Cycle 2:SD (n=6,1,6,4) | Cycle 2:PD (n=6,1,6,4) | Cycle 2:Missing (n=6,1,6,4) | Cycle 4:CR (n=5,1,5,3) | Cycle 4:PR (n=5,1,5,3) | Cycle 4:SD (n=5,1,5,3) | Cycle 4:PD (n=5,1,5,3) | Cycle 4:Missing (n=5,1,5,3) | Final visit:CR (n=6,2,6,5) | Final visit:PR (n=6,2,6,5) | Final visit:SD (n=6,2,6,5) | Final visit:PD (n=6,2,6,5) | Final visit:Missing (n=6,2,6,5) |
|---|
| Docetaxel 100 + Pertuzumab 420 | 0.0 | 0.0 | 75.0 | 25.0 | 0.0 | 0.0 | 0 | 66.7 | 33.3 | 0.0 | 0.0 | 0.0 | 20.0 | 60.0 | 20.0 |
,| Docetaxel 60 Plus (+) Pertuzumab 1050 | 0.0 | 0.0 | 83.3 | 16.7 | 0.0 | 0.0 | 0.0 | 80.0 | 20.0 | 0.0 | 0.0 | 0.0 | 33.3 | 50.0 | 16.7 |
,| Docetaxel 75 + Pertuzumab 1050 | 0.0 | 0.0 | 100.0 | 0 | 0.0 | 0.0 | 0.0 | 100.0 | 0.0 | 0.0 | 0.0 | 0.0 | 50.0 | 0.0 | 50.0 |
,| Docetaxel 75 + Pertuzumab 420 | 0.0 | 0.0 | 83.3 | 16.7 | 0.0 | 0.0 | 20.0 | 40.0 | 40.0 | 0.0 | 0.0 | 16.7 | 33.3 | 50.0 | 0.0 |
Mean Residence Time (MRT) of Pertuzumab
MRT is the average time that pertuzumab is present in the systemic circulation and is measured in days. (NCT02490475)
Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
| Intervention | days (Mean) |
|---|
| Cycle 1 (n=8,11,0) | Cycle 2 (n=7,0,10) |
|---|
| Pertuzumab 1050 | 17.8 | 29.5 |
,| Pertuzumab 420 | NA | 25.8 |
,| Pertuzumab 840 | 15.8 | NA |
Maximum Observed Plasma Concentration (Cmax) for Pertuzumab in Combination With Docetaxel
Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as micrograms per milliliter (μg/mL). (NCT02490475)
Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
| Intervention | μg/mL (Mean) |
|---|
| Cycle 1 (n=8,11,0) | Cycle 2 (n=7,0,10) |
|---|
| Pertuzumab 1050 | 301.0 | 368.0 |
,| Pertuzumab 420 | NA | 150.0 |
,| Pertuzumab 840 | 255.0 | NA |
Cmax for Docetaxel Alone and in Combination With Pertuzumab
Cmax refers to the maximum (or peak) serum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administrated and prior to the administration of a second dose and is measures as nanograms per milliliter (ng/mL). The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. (NCT02490475)
Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 (n=6,0,6,0,5,0) | Cycle 2 (n=0,6,0,6,0,4) |
|---|
| Docetaxel 100 + Pertuzumab 420 | NA | 4705 |
,| Docetaxel 100 Alone | 5450 | NA |
,| Docetaxel 60 + Pertuzumab 1050 | NA | 1695 |
,| Docetaxel 60 Alone | 1642 | NA |
,| Docetaxel 75 + Pertuzumab 420 | NA | 2722 |
,| Docetaxel 75 Alone | 3128 | NA |
Clearance (Cl) of Pertuzimab in Combination With Docetaxel
Clearance (expressed as volume/time) describes the removal of drug from a volume of plasma in a given unit of time (drug loss from the body). It is measured as milliliters per day (mL/day). (NCT02490475)
Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
| Intervention | mL/day (Mean) |
|---|
| Cycle 1 (n=8,11,0) | Cycle 2 (n=7,0,10) |
|---|
| Pertuzumab 1050 | 282 | 167 |
,| Pertuzumab 420 | NA | 169 |
,| Pertuzumab 840 | 329 | NA |
AUC(0-∞) for Docetaxel Alone and in Combination With Pertuzumab
The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as ng*h/mL. The pharmacokinetic parameters were derived by non-compartmental methods using WinNonLin version 5.0.1. (NCT02490475)
Timeframe: Cycles 1 and 2: Pre-dose, 30 and 55 minutes during dosing, 15 minutes, 30 minutes, 1, 2, 4, 8, and 23 hours Post-dose
| Intervention | ng*h/mL (Mean) |
|---|
| Cycle 1 (n=6,0,6,0,5,0) | Cycle 2 (n=0,6,0,6,0,4) |
|---|
| Docetaxel 100 + Pertuzumab 420 | NA | 5218 |
,| Docetaxel 100 Alone | 5930 | NA |
,| Docetaxel 60 + Pertuzumab 1050 | NA | 1734 |
,| Docetaxel 60 Alone | 1838 | NA |
,| Docetaxel 75 + Pertuzumab 420 | NA | 3496 |
,| Docetaxel 75 Alone | 3744 | NA |
AUC From Time Zero to Infinity (AUC [0-infinity]) for Pertuzumab in Combination With Docetaxel
The AUC0-infinity is calculated from time 0 (prior to administration of medication) to infinity (the time of complete elimination of the drug). The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as μg*day/mL. (NCT02490475)
Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
| Intervention | μg*day/mL (Mean) |
|---|
| Cycle 1 (n=8,11,0) | Cycle 2 (n=7,0,10) |
|---|
| Pertuzumab 1050 | 3951 | 6856 |
,| Pertuzumab 420 | NA | 2762 |
,| Pertuzumab 840 | 2796 | NA |
Area Under the Concentration Curve From Time Zero to the Last Visit (AUC [0-last]) for Pertuzumab in Combination With Docetaxel
The area under the plot of plasma concentration of drug against time after drug administration is defined as the area under the curve (AUC). The AUC0-last is calculated from time 0 (prior to administration of medication) to last measured data point. The AUC is of particular use in estimating the bioavailability of drugs, by measuring the extent of absorption. AUC is measured as micrograms times days per milliliter (μg*day/mL). (NCT02490475)
Timeframe: Cycle1: Day 2 Pre-dose and 15 minutes, 1.5, 4 and 8 hours Post-dose, and Days 3, 6, 9 and 16; Cycle 2: Day 1 Pre-dose and 15 minutes Post-dose on Days 1, 8, 15 and 22
| Intervention | μg*day/mL (Mean) |
|---|
| Cycle 1 (n=8,11,0) | Cycle 2 (n=7,0,10) |
|---|
| Pertuzumab 1050 | 2390 | 3500 |
,| Pertuzumab 420 | NA | 1491 |
,| Pertuzumab 840 | 1749 | NA |
Number of Participants With DLTs
DLTs were defined as any of the following: 1) Any non-hematological toxicity greter than or equal to (≥) Grade 3 according t0 CTCAE version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. (NCT02490475)
Timeframe: From Baseline until 4 weeks after the end of treatment
| Intervention | number of participants (Number) |
|---|
| Docetaxel 60 Plus (+) Pertuzumab 1050 | 0 |
| Docetaxel 75 + Pertuzumab 1050 | 2 |
| Docetaxel 75 + Pertuzumab 420 | 0 |
| Docetaxel 100 + Pertuzumab 420 | 2 |
Maximum Tolerated Dose (MTD) of Docetaxel in Combination of Pertuzumab
A prior dose level was defined as an MTD if at a certain dose level, there were greater than or equal to (≥) 2 out of 6 participants who had Dose Limiting Toxicities (DLTs). If there were no DLTs or DLTs were seen in less than (<) 2 participants in the highest dose level, that was considered as MTD. Participants received escalating doses of docetaxel and pertuzumab until DLTs were observed. DLTs were defined as any of the following: 1) Any non-hematological toxicity ≥ Grade 3 according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 except for fever, chills and flu-like symptoms, in spite of adequate toxicity management, 2) Grade 4 neutropenia lasting greater than (>) 7 days, 3) Febrile neutropenia, 4) Thrombocytopenia Grade 4 or any thrombocytopenia requiring platelet transfusion or 5) Any subjectively intolerable toxicity felt by the investigator to be related to either one of the compounds. (NCT02490475)
Timeframe: Cycle 1 Up to Day 15
| Intervention | mg/m^2 (Number) |
|---|
| Entire Study Population | 75.0 |
Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI)
The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging. (NCT02494713)
Timeframe: baseline
| Intervention | cc (Median) |
|---|
| ADT + Chemotherapy | 19.3 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: Day 133, about 19 weeks after treatment initiation (but before prostatectomy)
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 0.055 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: Cycle 2 Day 57, about 16 weeks after treatment initiation (but before prostatectomy)
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 0.15 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: Cycle 2 Day 1, about 8 weeks after treatment initiation (but before prostatectomy)
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 0.4 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: about 68 weeks after treatment initiation (about 48 weeks after prostatectomy)
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 0.1 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: baseline
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 58.7 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: about 44 weeks after treatment initiation (about 24 weeks after prostatectomy)
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 0.35 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: about 20 weeks after treatment initiation (day of prostatectomy)
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 0.01 |
Efficacy as Measured by Pathologic Response
Pathologic response is defined by percentage of tumor burden remaining at time of prostate removal. Percentage of tumor burden is measured based on a pathologist's assessment of the prostate tissue removed and visual estimate of how much tumor there is in the prostate. (NCT02494713)
Timeframe: Day of prostate removal, which is about 5 months following the day participant signed consent.
| Intervention | percentage of tumor burden remaining (Median) |
|---|
| ADT + Chemotherapy | 30 |
Efficacy as Measured by Prostate-specific Antigen (PSA) Levels
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02494713)
Timeframe: about 32 weeks after treatment initiation (about 12 weeks after prostatectomy)
| Intervention | ng/mL (Median) |
|---|
| ADT + Chemotherapy | 0.01 |
Efficacy as Measured by Volume of the Prostate Tumor as Assessed by Multiparametric Prostate Magnetic Resonance Imaging (mpMRI)
The volume of the prostate tumor was measured by a radiologist's assessment of multiparametric prostate magnetic resonance imaging. (NCT02494713)
Timeframe: post treatment but prior to prostatectomy (about 25 days after the end of treatment)
| Intervention | cc (Median) |
|---|
| ADT + Chemotherapy | 3.75 |
Safety of Drug Regimen as Measured by Number of Adverse Events
Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy. (NCT02494713)
Timeframe: From the time participant first initiates ADT plus chemotherapy until participant's completion of neoadjuvant ADT plus chemotherapy.
| Intervention | adverse event (Number) |
|---|
| ADT + Chemotherapy | 119 |
Surgical Morbidity as Measured by Number of Adverse Events
Number of adverse events was measured as a count of all participant adverse events that occurred from the time participant first initiates ADT plus chemotherapy until the participant was taken off-study or the study was stopped, an average of 20 months (NCT02494713)
Timeframe: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 20 months
| Intervention | adverse event (Number) |
|---|
| ADT + Chemotherapy | 119 |
Percentage of Participants With Radiographic Progression-free Survival at 6 Months (Phase 1b/2 RP2D)
Radiographic progression-free survival will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The percent of participants has been estimated using the Kaplan-Meier product limit method. Duration will be measured from day 1 of study treatment to first date of radiographic progression or death, whichever occurs first, for all Phase 1b or Phase 2 participants receiving the RP2D. Participants who discontinue study therapy for toxicity, withdrawal from study, or prostate-specific antigen (PSA)-only progression, will be censored at the date of last radiographic tumor assessment for this analysis. Patients who discontinue therapy for evidence of clinical progression/clinical deterioration will be included in this analysis. (NCT02494921)
Timeframe: Up to 6 months
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Phase 1b/2 RP2D) | 65.8 |
Prostate-Specific Antigen (PSA) Response Rate (Phase 1b/2 RP2D)
PSA progression occurs when the PSA value has increased 25% or greater above nadir and an absolute increase of 2 ng/mL or more from the nadir is documented. Where no decline is observed, PSA progression similarly occurs when a 25% increase from baseline value along with an increase in absolute value of 2 ng/mL or more per the Prostate Cancer Working Group 2 (PCWG2) Criteria. (NCT02494921)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Phase 1b/2 RP2D) | 32 |
Mean Maximum Serum Concentration of Ribociclib (Cmax) (Phase 1b)
The maximum concentration (Cmax) is shown to reflect not only the rate but also the extent of absorption. The mean Cmax for serum concentration of ribociclib will be reported using descriptive statistics for all participants in Phase 1b who received at least one dose of study treatment and completed a serum blood draw. (NCT02494921)
Timeframe: Pre-dose on day 1, and 1, 2, 4, and 24 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| 400 mg Ribociclib |
|---|
| Treatment (Phase 1b, RP2D) | 393.6 |
RP2D of Docetaxel (Phase 1b)
The RP2D of docetaxel will be reported when used in combination with ribociclib and prednisone based upon evaluation of dose-limiting toxicities (DLTs) and adverse events for all participants in the Phase Ib group. Per Investigator discretion, the RP2D schedule of docetaxel and ribociclib may be established in the absence of reaching MTD, based on the cumulative safety data of the treatment regimen. (NCT02494921)
Timeframe: Up to 2 years
| Intervention | mg/m^2 (Number) |
|---|
| Treatment (Phase 1b) | 60 |
Mean Area Under Curve (AUC) 0-24 Hour (Phase 1b)
The estimated AUC for serum concentration of ribociclib for a 24 hour interval after dose will be reported using descriptive statistics for all participants in Phase 1b who received at least one dose of study treatment and completed a serum blood draw. (NCT02494921)
Timeframe: Pre-dose on day 1, and 1, 2, 4, and 24 hours post-dose
| Intervention | ng*hrs/mL (Mean) |
|---|
| 400 mg ribociclib |
|---|
| Treatment (Phase 1b, RP2D) | 6531.6 |
Mean Area Under Curve (AUC) 0-24 Hour (Phase 1b)
The estimated AUC for serum concentration of ribociclib for a 24 hour interval after dose will be reported using descriptive statistics for all participants in Phase 1b who received at least one dose of study treatment and completed a serum blood draw. (NCT02494921)
Timeframe: Pre-dose on day 1, and 1, 2, 4, and 24 hours post-dose
| Intervention | ng*hrs/mL (Mean) |
|---|
| 200 mg ribociclib | 300 mg ribociclib |
|---|
| Treatment (Phase 1b, Non-RP2D) | 2909 | 3340.3 |
Maximally Tolerated Dose (MTD) (Phase 1b)
Maximally tolerated dose (MTD) of ribociclib in combination with docetaxel and prednisone is based upon evaluation of dose-limiting toxicities (DLTs) and adverse events for all participants who received treatment in Phase Ib. If 1 of 3 participants in a cohort experiences a DLT, then the cohort will be expanded to treat an additional 3 participants. If only 1 of 6 participants experiences a DLT, the next cohort of participants will be treated at the next higher dose level. If 2 or more participants in a cohort experience a DLT, then MTD has been exceeded and the previous dose level will be considered the MTD. If more than 1 of 6 patients experience a DLT at dose level IA then the study will be terminated, as the MTD cannot be determined and de-escalation from dose level IA is not planned. Per Investigator discretion the Recommended Phase 2 Dose (RP2D) schedule of ribociclib and docetaxel may be established in the absence of reaching MTD. (NCT02494921)
Timeframe: Up to 2 years
| Intervention | mg/m^2 (Number) |
|---|
| Treatment (Phase 1b) | NA |
Mean Maximum Serum Concentration of Ribociclib (Cmax) (Phase 1b)
The maximum concentration (Cmax) is shown to reflect not only the rate but also the extent of absorption. The mean Cmax for serum concentration of ribociclib will be reported using descriptive statistics for all participants in Phase 1b who received at least one dose of study treatment and completed a serum blood draw. (NCT02494921)
Timeframe: Pre-dose on day 1, and 1, 2, 4, and 24 hours post-dose
| Intervention | ng/mL (Mean) |
|---|
| 200 mg Ribociclib | 300 mg Ribociclib |
|---|
| Treatment (Phase 1b, Non-RP2D) | 207.5 | 289.8 |
Objective Response Rate (ORR) (Phase1b/2 RP2D)
ORR will be assessed using RECIST version 1.1 criteria, and defined as participants who were determined to have demonstrated a complete response (CR) and/or partial response (PR). Participants must have measurable disease at baseline with at least one restaging scan on treatment to be included in the analysis. (NCT02494921)
Timeframe: Up to 2 years
| Intervention | percentage of participants (Number) |
|---|
| Treatment (Phase 1b/2 RP2D) | 23.1 |
Incidence of Grade 3 and 4 Neutropenia and Febrile Neutropenia
The incidence of grade 3 and 4 neutropenia and febrile neutropenia in cycles following PK adjustment (cycles 2-4) will be compared with cycle 1 and historical non-PK guided therapy using the Wilcoxon-Rank sum assessment. (NCT02502864)
Timeframe: Up to 6 months
| Intervention | Participants (Count of Participants) |
|---|
| Participants with Grade 3 or 4 neutropenia | Participants with Febrile neutropenia |
|---|
| Standard of Care + Surveys | 2 | 0 |
Rate of Achieving Targeted Area Under the Curve (AUC)
Rate of PK guided dosing of docetaxel chemotherapy improving the ability to achieve a targeted AUC ( 2.5-3.7 mg*hr/L) within 4 cycles of therapy in patients > 65 years of age with breast cancer receiving TC (docetaxel and cyclophosphamide) as compared with historical non-PK guided therapy from patients receiving a similar regimen. (NCT02502864)
Timeframe: Cycle 4 - Up to 6 months
| Intervention | Participants (Count of Participants) |
|---|
| AUC mg*hr/L: 2.5-3.7 | AUC mg*hr/L: <2.5 |
|---|
| Standard of Care + Surveys | 5 | 3 |
Number of Participants With Adverse Events Determined by Laboratory Assessments and Physical Examinations
"To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolomide with 30 days of last dose in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy.~• To determine safety profile of Vigil immunotherapy in combination with irinotecan and temozolimidetemozolomide in patients with metastatic Ewing's sarcoma refractory or intolerant to at least 1 prior line of systemic chemotherapy." (NCT02511132)
Timeframe: 30 days of last treatment dosing
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: Vigil Alone | 5 |
| Part 1: Gemcitabine and Docetaxel | 6 |
| Part 2: Vigil in Combination With Temozolomide and Irinotecan | 9 |
Overall Survival
OS is defined as time from randomization to death or to the date of last follow-up. The date of last follow-up confirming survival will be used as the censoring date for subjects who are alive and/or do not have a known date of death. (NCT02511132)
Timeframe: Estimated median 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: Vigil Alone | 3 |
| Part 1: Gemcitabine and Docetaxel | 6 |
| Part 2: Vigil in Combination With Temozolomide and Irinotecan | 5 |
Progression Free Survival
Progression Free Survival (PFS) is defined as the time from randomization to the event of disease recurrence/progression defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) or death due to any cause. To determine the progression free survival of subjects dosed with Vigil immunotherapy in combination with irinotecan and temozolomide. (NCT02511132)
Timeframe: Estimated median 1.3 years
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: Vigil Alone | 5 |
| Part 1: Gemicitabine and Docetaxel | 6 |
| Part 2: Vigil in Combination With Temozolomide and Irinotecan | 9 |
Number of Participates With a Decline in Prostate-specific Antigen From Their Baseline Measurement
prostate-specific antigen decline will be defined as ≥ 50% from baseline measurement (NCT02516670)
Timeframe: up to 24 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (Docetaxel, Ascorbic Acid) | 13 |
| Arm B (Docetaxel, Placebo) | 5 |
Radiographic Progression Free Survival (rPFS)
To determine the rPFS of participates that receive at least one dose of ascorbic acid compared to those who received placebo (NCT02516670)
Timeframe: Up to 3 years
| Intervention | months (Median) |
|---|
| Arm A (Docetaxel, Ascorbic Acid) | 10.12 |
| Arm B (Docetaxel, Placebo) | 9.97 |
Number of Participants With Adverse Events
Number of participants experiencing fatigue, nausea, bone pain, and anorexia as defined by CTCAE 4.0 (NCT02516670)
Timeframe: Up to 30 days after the last dose of study drug
| Intervention | Participants (Count of Participants) |
|---|
| fatigue | nausea | bone pain | anorexia |
|---|
| Arm A (Docetaxel, Ascorbic Acid) | 25 | 17 | 2 | 12 |
,| Arm B (Docetaxel, Placebo) | 11 | 6 | 2 | 2 |
Number of Serious Adverse Events
"Number of serious adverse events of all types as defined by Common Terminology Criteria for Adverse Events 4.0.~A serious adverse event is an undesirable sign, symptom, or medical condition that:~Results in death~Is life threatening~Requires inpatient hospitalization or causes prolongation of existing hospitalization for >24 hours~Results in persistent or significant disability/incapacity~Is a congenital anomaly/birth defect~Is an important medical event" (NCT02516670)
Timeframe: Up to 30 days after last dose of study drug
| Intervention | events (Number) |
|---|
| grade 1 | grade 2 | grade 3 | grade 4 | grade 5 |
|---|
| Arm A (Docetaxel, Ascorbic Acid) | 0 | 4 | 18 | 3 | 0 |
,| Arm B (Docetaxel, Placebo) | 0 | 0 | 6 | 0 | 0 |
Average Number of Times Docetaxel Had Dose Reductions
The number of dose reductions and total number of completed cycles will be summarized by study arm. (NCT02516670)
Timeframe: Up to 24 weeks
| Intervention | dose reductions (Mean) |
|---|
| Arm A (Docetaxel, Ascorbic Acid) | 7 |
| Arm B (Docetaxel, Placebo) | 9 |
Number of Participates Experiencing Serious Adverse Events (SAE)
Number of serious adverse events defined as grade 3 or higher (fatigue, nausea, bone pain, and anorexia) in participates as defined by CTCAE 4.0 (NCT02516670)
Timeframe: Up to 24 weeks
| Intervention | Participants (Count of Participants) |
|---|
| fatigue | nausea | bone pain | anorexia |
|---|
| Arm A (Docetaxel, Ascorbic Acid) | 0 | 0 | 0 | 1 |
,| Arm B (Docetaxel, Placebo) | 0 | 0 | 0 | 0 |
Change in Quality of Life (QoL) as Measured by the FACT-P Questionnaire
The (FACT-P) is made up of 39 question, with the total score ranging between 0 and 156 with 0 being the best and 156 as the worst. (NCT02516670)
Timeframe: Up to course 6 of therapy (18 weeks)
| Intervention | score on a scale (Mean) |
|---|
| Arm A (Docetaxel, Ascorbic Acid) | 116.4580 |
| Arm B (Docetaxel, Placebo) | 113.9834 |
Survival
The Kaplan-Meier method will be used to estimate time to event distributions for survival. Survival will be defined as from the first date of therapy until the date of death from any cause. (NCT02524275)
Timeframe: First date of therapy until the date of death from any cause, assessed up to 5 years
| Intervention | days (Median) |
|---|
| Treatment (Docetaxel, Capecitabine) | 264.5 |
Overall Response Rate of Complete or Partial Response
The response rates of complete or partial response rate as defined by the Response Evaluation Criteria for Solid Tumors at 15 weeks of a chemotherapy regimen involving docetaxel and capecitabine as front line therapy at 95% confidence interval. Complete Response (CR): the 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 (NCT02524275)
Timeframe: At 15 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Docetaxel, Capecitabine) | 1 |
Progression-free Survival
The Kaplan-Meier method will be used to estimate time to event distributions for progression-free survival. Progression-free survival will be defined as from the first date of therapy until the first notation of clinical progression, relapse or death from any cause. (NCT02524275)
Timeframe: First date of therapy until the first notation of clinical progression, relapse or death from any cause, assessed up to 5 years
| Intervention | days (Median) |
|---|
| Treatment (Docetaxel, Capecitabine) | 211 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel/Carboplatin | 10 |
Number of Participants With at Least 1 ≥ Grade 3 TEAE in Part 1
"An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. There are 5 grades of the CTCAE; grade refers to severity. Grade 5 is the most severe, grade 1 is the least severe. As per version 4.0 of the CTCAE, Grade 3 = AE with severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4 = AE with life-threatening consequences; urgent intervention indicated and Grade 5 = Death related to AE." (NCT02551055)
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)
| Intervention | participants (Number) |
|---|
| MLN1117 300 mg + Alisertib | 4 |
| MLN1117 600 mg + Alisertib | 4 |
| MLN1117 300 mg + Paclitaxel | 2 |
| MLN1117 600 mg + Paclitaxel | 2 |
| MLN1117 300 mg + TAK-659 | 6 |
| MLN1117 200 mg + Docetaxel | 2 |
| MLN1117 300 mg + Docetaxel | 4 |
Number of Participants With at Least 1 TEAE and Serious TEAE in Part 1 and 2
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is 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/birth defect; or a medically important event. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT02551055)
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)
| Intervention | participants (Number) |
|---|
| AE | SAE |
|---|
| MLN1117 200 mg + Docetaxel | 2 | 2 |
,| MLN1117 300 mg + Alisertib | 4 | 2 |
,| MLN1117 300 mg + Docetaxel | 4 | 4 |
,| MLN1117 300 mg + Paclitaxel | 3 | 1 |
,| MLN1117 300 mg + TAK-659 | 7 | 5 |
,| MLN1117 600 mg + Alisertib | 6 | 3 |
,| MLN1117 600 mg + Paclitaxel | 6 | 2 |
Number of Participants With at Least 1 Dose Modification Due to AE in Part 1
A decision regarding which study drug requires dose modification is dependent upon the toxicity, its onset, and time course. The causal relationship of each AE should will be assessed in relation to MLN1117 and to the combination agent in each cohort so that dose modifications can be made accordingly. Intrapatient dose reductions of MLN1117 are not permitted during Part 1 Cycle 1 unless the participant experiences a DLT attributed to MLN1117. Per dose modification guidelines, participants who have the study drug held because of treatment related or possibly related AEs may resume study drug treatment after resolution of the AE but may either maintain the same dose level or have doses of study drug reduced (dose reduction) by at least 1 dose level and if needed, by 2 dose levels. When a dose reduction of MLN1117 occurs, the MLN1117 dose will be reduced to the next lower dose that has been established as a safe dose during dose escalation (Part 1). (NCT02551055)
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)
| Intervention | participants (Number) |
|---|
| MLN1117 300 mg + Alisertib | 0 |
| MLN1117 600 mg + Alisertib | 1 |
| MLN1117 300 mg + Paclitaxel | 1 |
| MLN1117 600 mg + Paclitaxel | 0 |
| MLN1117 300 mg + TAK-659 | 4 |
| MLN1117 200 mg + Docetaxel | 0 |
| MLN1117 300 mg + Docetaxel | 1 |
Number of Participants Who Experienced Cycle 1 Dose Limiting Toxicity (DLT) in Part 1
Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. DLT defined as any of following considered related to any of treatment by investigator: Grade 4 neutropenia (absolute neutrophil count <500 cells/mm^3) for >7 days; ≥ Grade 3 neutropenia with coincident fever or infection; Grade 4 thrombocytopenia for >7 days; Grade 3 thrombocytopenia with clinically significant bleeding; Platelet count <10,000/mm^3 at any time; Delay in initiation of subsequent therapy cycle by >7 days due to treatment-related toxicity; ≥Grade 3 nonhematological toxicity except Grade 3 arthralgia/myalgia, fatigue that lasts <1 month, diarrhea, fasting hyperglycemia lasting ≤14 days, rash lasting ≤7 days and any other Grade 3 nonhematological toxicity that could be safely, reliably controlled to ≤Grade 1 with appropriate treatment; ≥ Grade 2 nonhematologic toxicities that are considered by investigator to be related to study drugs and dose-limiting. (NCT02551055)
Timeframe: Up to Cycle 1 (28 days for MLN1117+TAK-659, MLN1117+Alisertib, MLN1117+Paclitaxel or 21 days for MLN1117+Docetaxel)
| Intervention | participants (Number) |
|---|
| MLN1117 300 mg + Alisertib | 0 |
| MLN1117 600 mg + Alisertib | 1 |
| MLN1117 300 mg + Paclitaxel | 0 |
| MLN1117 600 mg + Paclitaxel | 0 |
| MLN1117 300 mg + TAK-659 | 1 |
| MLN1117 200 mg + Docetaxel | 0 |
| MLN1117 300 mg + Docetaxel | 1 |
Number of Participants With at Least 1 Treatment-Emergent Adverse Event (TEAE) in Part 1
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT02551055)
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)
| Intervention | participants (Number) |
|---|
| MLN1117 300 mg + Alisertib | 4 |
| MLN1117 600 mg + Alisertib | 6 |
| MLN1117 300 mg + Paclitaxel | 3 |
| MLN1117 600 mg + Paclitaxel | 6 |
| MLN1117 300 mg + TAK-659 | 7 |
| MLN1117 200 mg + Docetaxel | 2 |
| MLN1117 300 mg + Docetaxel | 4 |
Plasma Concentration of MLN1117-1003
(NCT02551055)
Timeframe: MLN1117 300 mg + Alisertib arms: Cycle 1 Day 3; MLN1117 300 mg + Paclitaxel arms and MLN1117 200 mg + Docetaxel arms: Cycle 1 Day 2; MLN1117 300 mg + TAK-659 arm: Cycle 1 Days 1 and 17
| Intervention | ng/mL (Mean) |
|---|
| Day 1: Predose | Day 1: 0.5 Hour Postdose | Day 1: 1 Hour Postdose | Day 1: 2 Hours Postdose | Day 1: 3 Hours Postdose | Day 1: 4 Hours Postdose | Day 1: 6 Hours Postdose | Day 1: 8 Hours Postdose | Day 1: 24 Hours Postdose | Day 2: Predose | Day 2: 0.5 Hour Postdose | Day 2: 1 Hour Postdose | Day 2: 2 Hours Postdose | Day 2: 3 Hours Postdose | Day 2: 4 Hours Postdose | Day 2: 6 Hours Postdose | Day 2: 8 Hours Postdose | Day 2: 24 Hours Postdose | Day 3: Predose | Day 3: 0.5 Hour Postdose | Day 3: 1 Hour Postdose | Day 3: 2 Hours Postdose | Day 3: 3 Hours Postdose | Day 3: 4 Hours Postdose | Day 3: 6 Hours Postdose | Day 3: 8 Hours Postdose | Day 3: 24 Hours Postdose | Day 17: Predose | Day 17: 0.5 Hour Postdose | Day 17: 1 Hour Postdose | Day 17: 2 Hours Postdose | Day 17: 3 Hours Postdose | Day 17: 4 Hours Postdose | Day 17: 6 Hours Postdose | Day 17: 8 Hours Postdose |
|---|
| MLN1117 200 mg + Docetaxel | NA | NA | NA | NA | NA | NA | NA | NA | NA | 0.00 | 3240.00 | 3165.00 | 4615.00 | 4355.00 | 3725.00 | 3085.00 | 3025.00 | 717.00 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| MLN1117 300 mg + Alisertib | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 2177.50 | 3225.00 | 5010.00 | 5007.50 | 4815.00 | 4797.50 | 4777.50 | 4320.00 | 2217.33 | NA | NA | NA | NA | NA | NA | NA | NA |
,| MLN1117 300 mg + Docetaxel | NA | NA | NA | NA | NA | NA | NA | NA | NA | 0.00 | 1333.05 | 1554.00 | 1456.23 | 1598.75 | 1475.75 | 1417.75 | 1443.25 | 420.80 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| MLN1117 300 mg + Paclitaxel | NA | NA | NA | NA | NA | NA | NA | NA | NA | 0.00 | 1762.00 | 3840.00 | 4066.67 | 3653.33 | 3206.67 | 2720.00 | 2536.67 | 592.67 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
,| MLN1117 300 mg + TAK-659 | 0.00 | 675.04 | 2171.00 | 3054.14 | 3315.29 | 3164.71 | 2726.71 | 2466.29 | 1045.17 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 978.33 | 2893.67 | 5596.67 | 5583.33 | 5116.67 | 5066.67 | 4293.33 | 4330.00 |
,| MLN1117 600 mg + Alisertib | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | 3178.82 | 4554.80 | 5070.60 | 6235.80 | 5650.00 | 4719.20 | 4501.80 | 4354.80 | 2357.42 | NA | NA | NA | NA | NA | NA | NA | NA |
,| MLN1117 600 mg + Paclitaxel | NA | NA | NA | NA | NA | NA | NA | NA | NA | 0.00 | 1701.17 | 3261.83 | 3934.00 | 3753.50 | 3994.67 | 4311.67 | 3246.00 | 1279.83 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
Number of Participants With at Least 1 Treatment-Emergent Serious Adverse Event (SAE) in Part 1
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A SAE is 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/birth defect; or a medically important event. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. (NCT02551055)
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)
| Intervention | participants (Number) |
|---|
| MLN1117 300 mg + Alisertib | 2 |
| MLN1117 600 mg + Alisertib | 3 |
| MLN1117 300 mg + Paclitaxel | 1 |
| MLN1117 600 mg + Paclitaxel | 2 |
| MLN1117 300 mg + TAK-659 | 5 |
| MLN1117 200 mg + Docetaxel | 2 |
| MLN1117 300 mg + Docetaxel | 4 |
Number of Participants With Dose Delays, Dose Reductions, and Dose Interruptions Due To AE in Part 1 and 2
Per dose modification guidelines, participants who have the study drug held because of treatment related or possibly related AEs may resume study drug treatment after resolution of the AE but may either maintain the same dose level or have doses of study drug reduced (dose reduction) by at least 1 dose level and if needed, by 2 dose levels. (NCT02551055)
Timeframe: From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)
| Intervention | Participants (Count of Participants) |
|---|
| Dose delay due to AE | Dose reduction due to AE | Dose interruption due to AE |
|---|
| MLN1117 200 mg + Docetaxel | 0 | 0 | 0 |
,| MLN1117 300 mg + Alisertib | 0 | 0 | 0 |
,| MLN1117 300 mg + Docetaxel | 0 | 1 | 0 |
,| MLN1117 300 mg + Paclitaxel | 0 | 1 | 1 |
,| MLN1117 300 mg + TAK-659 | 1 | 4 | 0 |
,| MLN1117 600 mg + Alisertib | 0 | 1 | 0 |
,| MLN1117 600 mg + Paclitaxel | 0 | 0 | 0 |
Efficacy as Measured by PSA Level
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02560051)
Timeframe: Cycle 2 Day 1, which is about 8 weeks after treatment initiation
| Intervention | ng/mL (Median) |
|---|
| Definitive Local Therapy | 0.01 |
| Nodal Only/Low-volume Bone | 0.3 |
| High Volume/no Prior tx | 3.8 |
Efficacy as Measured by PSA Level
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02560051)
Timeframe: Cycle 3 Day 1, which is about 16 weeks after treatment initiation
| Intervention | ng/mL (Median) |
|---|
| Definitive Local Therapy | 0.01 |
| Nodal Only/Low-volume Bone | 0.1 |
| High Volume/no Prior tx | 0.9 |
Efficacy as Measured by PSA Level
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02560051)
Timeframe: Cycle 4 Day 1, which is about 24 weeks after treatment initiation
| Intervention | ng/mL (Median) |
|---|
| Nodal Only/Low-volume Bone | 0.01 |
| High Volume/no Prior tx | 0.55 |
Quality of Life Measure by FACT-P Scale
"The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL.~The time point is about 12 weeks after completion of the last cycle. For the arm completing 3 cycles, the time point is 36 weeks after treatment initiation. For the arm completing 4 cycles, the time point is 44 weeks after treatment initiation. For the arm completing 5 cycles, the time point is 52 weeks after treatment initiation." (NCT02560051)
Timeframe: about 12 weeks after completion of the last cycle
| Intervention | units on a scale (Median) |
|---|
| Definitive Local Therapy | 94 |
| Nodal Only/Low-volume Bone | 118 |
| High Volume/no Prior tx | 99 |
Quality of Life Measure by FACT-P Scale
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL. (NCT02560051)
Timeframe: post cycle 1, which is about 8 weeks after treatment initiation
| Intervention | units on a scale (Median) |
|---|
| Definitive Local Therapy | 97 |
| Nodal Only/Low-volume Bone | 99 |
| High Volume/no Prior tx | 105 |
Quality of Life Measure by FACT-P Scale
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL. (NCT02560051)
Timeframe: post cycle 3, which is about 24 weeks after treatment initiation
| Intervention | units on a scale (Median) |
|---|
| Definitive Local Therapy | 79 |
| Nodal Only/Low-volume Bone | 94 |
| High Volume/no Prior tx | 114 |
Quality of Life Measure by FACT-P Scale
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL. (NCT02560051)
Timeframe: post cycle 4, which is about 32 weeks after treatment initiation
| Intervention | units on a scale (Median) |
|---|
| Nodal Only/Low-volume Bone | 96 |
| High Volume/no Prior tx | 113 |
Safety of Drug Regimen as Measured by Number of Adverse Events
(NCT02560051)
Timeframe: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months
| Intervention | adverse event (Number) |
|---|
| Definitive Local Therapy | 115 |
| Nodal Only/Low-volume Bone | 270 |
| High Volume/no Prior tx | 166 |
Efficacy as Measured by PSA Level
"Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood.~The time point is the end of treatment, which is about about 8 weeks after the start of the last cycle. For the arm completing 3 cycles, the time point is 24 weeks after treatment initiation. For the arm completing 4 cycles, the time point is 32 weeks after treatment initiation. For the arm completing 5 cycles, the time point is 40 weeks after treatment initiation." (NCT02560051)
Timeframe: end of treatment, which is about about 8 weeks after the start of the last cycle
| Intervention | ng/mL (Median) |
|---|
| Definitive Local Therapy | 0.01 |
| Nodal Only/Low-volume Bone | 0.01 |
| High Volume/no Prior tx | 1.4 |
Quality of Life Measure by FACT-P Scale
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL. (NCT02560051)
Timeframe: post cycle 5, which is about about 40 weeks after treatment initiation
| Intervention | units on a scale (Median) |
|---|
| High Volume/no Prior tx | 107 |
Efficacy as Measured by Number Who Progressed
Progression defined as increase in Prostate Specific Antigen (PSA) >0.3 ng/mL over 2 measurements or larger/new lesion (NCT02560051)
Timeframe: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months
| Intervention | Participants (Count of Participants) |
|---|
| Definitive Local Therapy | 0 |
| Nodal Only/Low-volume Bone | 0 |
| High Volume/no Prior tx | 2 |
Efficacy as Measured by Number Who PSA Progressed
PSA progression defined as increase in Prostate Specific Antigen (PSA) >0.3 ng/mL over 2 measurements (NCT02560051)
Timeframe: From the time the participant signs the informed consent until the participant was taken off-study or the study was stopped, an average of 10 months
| Intervention | Participants (Count of Participants) |
|---|
| Definitive Local Therapy | 0 |
| Nodal Only/Low-volume Bone | 0 |
| High Volume/no Prior tx | 1 |
Efficacy as Measured by Number of Participants With Pathology/Biopsy Positive for Disease
(NCT02560051)
Timeframe: about 10 months after treatment initiation
| Intervention | Participants (Count of Participants) |
|---|
| Definitive Local Therapy | 0 |
| Nodal Only/Low-volume Bone | 3 |
| High Volume/no Prior tx | 3 |
Efficacy as Measured by PSA Level
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02560051)
Timeframe: baseline
| Intervention | ng/mL (Median) |
|---|
| Definitive Local Therapy | 5.7 |
| Nodal Only/Low-volume Bone | 15.8 |
| High Volume/no Prior tx | 90.7 |
Efficacy as Measured by PSA Level
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02560051)
Timeframe: Cycle 5 Day 1, which is about about 32 weeks after treatment initiation
| Intervention | ng/mL (Median) |
|---|
| High Volume/no Prior tx | 0.5 |
Quality of Life Measure by FACT-P Scale
The Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale is a tool used for assessing the health-related quality of life (QoL) in men with prostate cancer. It consists of 27 core items which assess patient function in four domains (Physical, Social/Family, Emotional, and Functional well-being), and it is further supplemented by 12 site specific items to assess for prostate-related symptoms. Each item is rated on a 0 to 4 Likert type scale, and then combined to produce a global QoL score, with a range of scores of 0 to 156. Higher scores represent better QoL. (NCT02560051)
Timeframe: post cycle 2, which is about 16 weeks after treatment initiation
| Intervention | units on a scale (Median) |
|---|
| Definitive Local Therapy | 94 |
| Nodal Only/Low-volume Bone | 97 |
| High Volume/no Prior tx | 102 |
Efficacy as Measured by PSA Level
Prostate-specific antigen, or PSA, is a protein produced by normal, as well as malignant, cells of the prostate gland. The PSA test measures the level of PSA in a man's blood. For this test, a blood sample is sent to a laboratory for analysis. The results are reported as nanograms of PSA per milliliter (ng/mL) of blood. (NCT02560051)
Timeframe: Cycle 1 Day 1, which is the day of treatment initiation
| Intervention | ng/mL (Median) |
|---|
| Definitive Local Therapy | 5.7 |
| Nodal Only/Low-volume Bone | 9.7 |
| High Volume/no Prior tx | 90.7 |
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
OS was defined as the time from randomization to death due to any cause. Median OS in participants with a PD-L1 CPS ≥10 is presented. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 9.3 |
| Chemotherapy | 6.7 |
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1. The percentage of all participants who experienced a CR or PR is presented. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 13.1 |
| Chemotherapy | 6.7 |
Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
OS was defined as the time from randomization to death due to any cause. Median OS in participants with SCC of the esophagus is presented. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 8.2 |
| Chemotherapy | 7.1 |
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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 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 ≥1 new lesions was also considered PD. Median PFS as assessed by blinded independent central review per RECIST 1.1 in all participants is presented. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.1 |
| Chemotherapy | 3.4 |
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1. The percentage of participants with SCC of the esophagus who experienced a CR or PR is presented. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 16.7 |
| Chemotherapy | 7.4 |
Overall Survival (OS) in All Participants
OS was defined as the time from randomization to death due to any cause. Median OS in all participants is presented. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 7.1 |
| Chemotherapy | 7.1 |
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 does 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 who experienced ≥1 AE is presented. (NCT02564263)
Timeframe: Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years)
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 301 |
| Chemotherapy | 288 |
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR is presented. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 21.5 |
| Chemotherapy | 6.1 |
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS as assessed by blinded independent central review per RECIST 1.1 is presented for participants with SCC of the esophagus. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.2 |
| Chemotherapy | 3.1 |
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (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 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 ≥1 new lesions was also considered PD. Median PFS as assessed by blinded independent central review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10. (NCT02564263)
Timeframe: Through Final Analysis data cutoff date of 15-Oct-2018 (up to approximately 34 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.6 |
| Chemotherapy | 3.0 |
Number of Participants Discontinuing Study Treatment Due an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does 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 who discontinued study treatment due to an AE is presented. (NCT02564263)
Timeframe: Through End-of-Trial Analysis data cutoff date of 14-Mar-2022 (up to approximately 6 years)
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 40 |
| Chemotherapy | 42 |
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
| Intervention | Percent with PSA decline (Number) |
|---|
| Arm I (Sirolimus, Docetaxel, Carboplatin) | 36 |
| Arm II (Sirolimus, Docetaxel, Carboplatin) | 36 |
| Phase 1 Group | 50 |
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
| Intervention | Grade 3 or 4 AE (Number) |
|---|
| Arm I (Sirolimus, Docetaxel, Carboplatin) | 2 |
| Arm II (Sirolimus, Docetaxel, Carboplatin) | 2 |
| Phase 1 Group | 0 |
Progression-free Survival
"Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of Not Evaluable (NE)." (NCT02569242)
Timeframe: "(Earlier date on which either the overall response was assessed as PD or the subject died of any cause - Date of randomization + 1) / 30.4375."
| Intervention | months (Median) |
|---|
| Nivolumab Arm | 1.7 |
| Active Comparator Arm （Docetaxel/Paclitaxel） | 3.4 |
Overall Survival
(NCT02569242)
Timeframe: "(Date of death from any cause - Date of randomization + 1) / 30.4375. For subjects lost to follow-up and subjects who are alive at the time of data cutoff date, data will be censored at the time the subject was last confirmed to be alive."
| Intervention | months (Median) |
|---|
| Nivolumab Arm | 10.9 |
| Active Comparator Arm （Docetaxel/Paclitaxel） | 8.4 |
Duration of Response
"Please refer to the protocol, overall response and best overall response will be determined solely by imaging assessment according to the RECIST Guideline Version 1.1, and will not take into account any clinical/symptomatic progression. Evaluable imaging data will be overall response without an overall response of Not Evaluable (NE)." (NCT02569242)
Timeframe: "(Earlier date on which either the overall response was assessed as PD for the first time after confirmed response or the subject died of any cause - Date of first assessment of confirmed CR or PR + 1) / 30.4375."
| Intervention | months (Median) |
|---|
| Nivolumab Arm | 6.9 |
| Active Comparator Arm （Docetaxel/Paclitaxel） | 3.9 |
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
| Intervention | months (Median) |
|---|
| Group A, Cohort A, Nivo | 12.780 |
| Group A, Cohort A, Beva + Nivo | NA |
| Group A, Cohort A, Beva | 17.084 |
| Group A, Cohort B, Nivo | 12.912 |
| Group A, Cohort B, Peme + Nivo | 8.542 |
| Group A, Cohort B, Peme | 14.982 |
| Group B, Nivo | NA |
| Group B, BSC | NA |
| Group C, Nivo | 3.877 |
| Group C, ICC | 2.940 |
| Group D, Nivo + Erlo | 8.805 |
| Group D, Erlo | 10.152 |
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
| Intervention | Percentage of participants (Number) |
|---|
| Group A, Cohort A, Nivo | 23.1 |
| Group A, Cohort A, Beva + Nivo | 16.7 |
| Group A, Cohort A, Beva | 12.5 |
| Group A, Cohort B, Nivo | 29.4 |
| Group A, Cohort B, Peme + Nivo | 21.2 |
| Group A, Cohort B, Peme | 3.1 |
| Group B, Nivo | 18.8 |
| Group B, BSC | 5.9 |
| Group C, Nivo | 20.8 |
| Group C, ICC | 15.4 |
| Group D, Nivo + Erlo | 64.7 |
| Group D, Erlo | 62.5 |
| Group E | 23.1 |
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
| Intervention | Months (Median) |
|---|
| Group A, Cohort A, Nivo | 20.0 |
| Group A, Cohort A, Beva + Nivo | 30.8 |
| Group A, Cohort A, Beva | 18.1 |
| Group A, Cohort B, Nivo | 28.9 |
| Group A, Cohort B, Peme + Nivo | 17.4 |
| Group A, Cohort B, Peme | 18.4 |
| Group B, Nivo | NA |
| Group B, BSC | 13.6 |
| Group C, Nivo | 3.9 |
| Group C, ICC | 15.8 |
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
| Intervention | months (Median) |
|---|
| Group D, Nivo + Erlo | NA |
| Group D, Erlo | 34.8 |
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
| Intervention | months (Median) |
|---|
| Group E | 9.63 |
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
| Intervention | Months (Median) |
|---|
| Group A, Cohort A, Nivo | 15.0 |
| Group A, Cohort A, Beva + Nivo | 6.7 |
| Group A, Cohort A, Beva | 6.0 |
| Group A, Cohort B, Nivo | 5.9 |
| Group A, Cohort B, Peme + Nivo | 8.1 |
| Group A, Cohort B, Peme | 5.0 |
| Group B, Nivo | 9.6 |
| Group B, BSC | 2.3 |
| Group C, Nivo | 2.7 |
| Group C, ICC | 6.7 |
| Group D, Nivo + Erlo | 11.0 |
| Group D, Erlo | 11.0 |
Overall Response Rate
The objective response rate (ORR) per response evaluation criteria in solit tumors (RECIST v1.1) was defined as the sum of complete response or partial response assessed by RECIST (v1.1) and is presented as the percent of participants with 95% Confidence Intervals (CI). Complete response (CR) was considered if there was a dissapearance of all target lesions, any pathological lymph nodes (whether target or non-target) must have had a reduction in short axis to <10 mm. Partial response (PR) was considered if there was at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR. (NCT02574598)
Timeframe: from baseline to 2 months of treatment
| Intervention | percentage of responders (Number) |
|---|
| Docetaxel + MK-3475 | 42.5 |
| Docetaxel | 15.8 |
Percentage of Participants With Breast Pathologic Complete Response (bpCR), Defined as ypT0/is According to the AJCC Staging System as Assessed by the IRC
This bpCR was assessed by the IRC. bpCR was defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is, in accordance with current AJCC staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose bpCR assessment was missing or invalid were counted as not achieving bpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: At surgery (Cycle 4 Days 22-35)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 42.0 |
| Placebo, Trastuzumab, and Chemotherapy | 23.6 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Disease-Free Survival (DFS) at 1, 3, and 5 Years
Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for DFS at 1, 3 and 5 years. DFS = time from first date of no disease (i.e., date of surgery) to first documentation of one of the following events: Disease recurrence (local, regional, distant, or contralateral) after surgery or death from any cause. After treatment completion/discontinuation, follow-up data was collected every 3 months for 1 year and then every 6 months thereafter, until disease progression or recurrence or until 5 years after randomization of the last participant, whichever occurred first. Participants were considered to be disease-free if they underwent surgery and no recurrence of disease was reported thereafter. Data from participants who did not have an event at analysis were censored as of the date they were last known to be alive and event-free. (NCT02586025)
Timeframe: From surgery (Cycle 4: Days 22-35) to DFS event or date last known to be alive and event-free at 1, 3, and 5 years
| Intervention | estimate of percentage of participants (Number) |
|---|
| 1 Year | 3 Years | 5 Years |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 97.55 | 90.09 | 85.99 |
,| Placebo, Trastuzumab, and Chemotherapy | 92.08 | 81.10 | 75.02 |
Percentage of Participants Who Experienced a Primary Cardiac Event
A primary cardiac event is defined as heart failure (New York Heart Association [NYHA] Class III or NYHA Class IV) and a drop in left ventricular ejection fraction (LVEF) of at least 10 ejection fraction points from baseline and to below 50%. (NCT02586025)
Timeframe: From Baseline until end of study (up to 6 years)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 0 |
| Placebo, Trastuzumab, and Chemotherapy | 0 |
Change From Baseline in LVEF Over Time
LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. A normal LVEF ranges from 55% to 70%, as measured by echocardiogram (preferred) or MUGA scan. The same method was used throughout the study for each participant and preferably performed and evaluated by the same assessor. Here, we report the change from baseline in LVEF over time. (NCT02586025)
Timeframe: Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)
| Intervention | percentage points of LVEF (Mean) |
|---|
| Cycle 2 Day 1 | Cycle 4 Day 1 | Cycle 5 Day 1 | Cycle 8 Day 1 | Cycle 11 Day 1 | Cycle 20 Day 1 |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | -0.62 | -1.02 | -0.96 | -1.63 | -1.38 | -1.22 |
,| Placebo, Trastuzumab, and Chemotherapy | 0.29 | 0.09 | 0.07 | -1.18 | -0.65 | -1.18 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival (OS) at 1, 3, and 5 Years
Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at 1, 3 and 5 years. OS was defined as the time from randomization to death from any cause. After treatment completion/discontinuation, follow-up data was collected every 3 months for 1 year and then every 6 months thereafter, until disease progression or recurrence or until 5 years after randomization of the last participant, whichever occurred first. Data from participants who were alive at the time of the analysis was censored as of the last date they were known to be alive. (NCT02586025)
Timeframe: From Baseline to OS event or date last known to be alive at 1, 3, and 5 years
| Intervention | estimate of percentage of participants (Number) |
|---|
| 1 Year | 3 Years | 5 Years |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 99.54 | 97.01 | 93.86 |
,| Placebo, Trastuzumab, and Chemotherapy | 100.00 | 90.99 | 89.97 |
Percentage of Participants With tpCR as Assessed by the Local Pathologist
This tpCR was assessed by the local pathologist. 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 after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current AJCC staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: At surgery (Cycle 4 Days 22-35)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 39.3 |
| Placebo, Trastuzumab, and Chemotherapy | 20.9 |
Percentage of Participants With Total Pathologic Complete Response (tpCR) as Assessed by the Independent Review Committee (IRC)
This tpCR was assessed by the IRC. 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 after completion of neoadjuvant therapy and surgery (that is, ypT0/is, ypN0, in accordance with the current American Joint Committee on Cancer [AJCC] staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose tpCR assessment was missing or invalid were counted as not achieving tpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: At surgery (Cycle 4 Days 22-35)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 39.3 |
| Placebo, Trastuzumab, and Chemotherapy | 21.8 |
Maximum Change From Baseline in LVEF
LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. A normal LVEF ranges from 55% to 70%, as measured by echocardiogram (preferred) or MUGA scan. The same method was used throughout the study for each participant and preferably performed and evaluated by the same assessor. Here, we report the maximum change from baseline in LVEF at any point during the study. (NCT02586025)
Timeframe: Baseline; Day 1 of Cycles 2, 4, 5, 8, 11, and 20 (1 cycle = 21 days)
| Intervention | percentage points of LVEF (Mean) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | -6.55 |
| Placebo, Trastuzumab, and Chemotherapy | -6.20 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Event-Free Survival (EFS) at 1, 3, and 5 Years
Kaplan-Meier approach was used to estimate percentage of participants who were event-free for EFS at 1, 3 & 5 years. EFS=time from randomization to first documentation of one of the following events: PD (before surgery) as determined by investigator with RECIST v1.1. PD=at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum during the study (nadir) with inclusion of baseline. Any evidence of contralateral disease in situ was not identified as PD; Disease recurrence (local, regional, distant, or contralateral) after surgery; Death from any cause. After treatment completion/discontinuation, follow-up data was collected every 3 months for 1 year & then every 6 months thereafter, until disease progression/recurrence or until 5 years after randomization of last participant, whichever occurred first. Participants without an EFS event at time of analysis were censored as of the date they were last known to be alive & event-free. (NCT02586025)
Timeframe: From Baseline to EFS event or date last known to be alive and event-free at 1, 3, and 5 years
| Intervention | estimate of percentage of participants (Number) |
|---|
| 1 Year | 3 Years | 5 Years |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 98.62 | 88.85 | 84.80 |
,| Placebo, Trastuzumab, and Chemotherapy | 90.46 | 79.68 | 73.70 |
Percentage of Participants With an Objective Response (CR or PR) During Cycles 1-4, According to RECIST Version 1.1
An objective response was defined as the percentage of participants who achieved a CR or PR as the best tumor response during the neoadjuvant period (that is, during Cycles 1-4 prior to surgery), as determined by the investigator on the basis of RECIST version 1.1. CR=disappearance of all target lesions i.e., 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. No confirmation was required for objective response. Only participants with measurable disease at baseline were included in the analysis. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: At surgery (Cycle 4 Days 22-35)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 88.6 |
| Placebo, Trastuzumab, and Chemotherapy | 78.2 |
Percentage of Participants With at Least One Adverse Event (AE) During the Neoadjuvant Treatment Period
The percentage of participants who experienced at least one AE during the neoadjuvant period is reported here. An AE is any untoward medical occurrence in a clinical investigation participant who is administered a pharmaceutical product regardless of the causal attribution. 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. The neoadjuvant treatment period began after randomization upon receiving the first dose of any of the neoadjuvant study medications and ended before receiving the first dose of adjuvant study treatment. The duration of one treatment cycle is 21 days. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: Baseline up to end of Cycle 4 (1 cycle = 21 days)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 97.7 |
| Placebo, Trastuzumab, and Chemotherapy | 96.4 |
Percentage of Participants With at Least One Adverse Event During the Treatment-Free Follow-Up Period
The percentage of participants who experienced at least one adverse event during the treatment-free follow-up period is reported here. An AE is any untoward medical occurrence in a clinical investigation participant who is administered a pharmaceutical product regardless of the causal attribution. 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. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: From end of overall study treatment until disease progression or until 5 years after randomization of the last patient, whichever occurred first (up to 6 years)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 6.0 |
| Placebo, Trastuzumab, and Chemotherapy | 7.3 |
Percentage of Participants Who Experienced a Secondary Cardiac Event
A secondary cardiac event is defined as an asymptomatic or mildly symptomatic (NYHA Class II) drop in LVEF by multiple-gated acquisition (MUGA) scan or echocardiogram confirmed by a second LVEF assessment within approximately 3 weeks showing also a documented drop. A significant LVEF drop is defined as an absolute decrease of at least 10 points below the baseline measurement and to below 50%. (NCT02586025)
Timeframe: From Baseline until end of study (up to 6 years)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 0 |
| Placebo, Trastuzumab, and Chemotherapy | 0 |
Percentage of Participants With at Least One AE During the Adjuvant Treatment Period
Percentage of participants who experienced at least one adverse event during the adjuvant period is reported here. An AE is any untoward medical occurrence in a clinical investigation participant who is administered a pharmaceutical product regardless of the causal attribution. An adverse event was therefore any unfavorable 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. Adjuvant treatment period began after primary surgery, upon receiving the first dose of any of the adjuvant study medications. It ended 42 days after last dose of adjuvant study treatment upon treatment completion or discontinuation. 1 Cycle=21 days. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: From Cycle 5 (1 cycle = 21 days) up to 42 days after the last dose in Cycle 20 Day 1 (approximately 1 year)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 98.1 |
| Placebo, Trastuzumab, and Chemotherapy | 98.1 |
Percentage of Participants With bpCR as Assessed by the Local Pathologist
This bpCR was assessed by the local pathologist. bpCR was defined as the absence of any residual invasive cancer on the hematoxylin and eosin evaluation of the resected breast specimen after completion of neoadjuvant therapy and surgery (that is, ypT0/is in accordance with current AJCC staging system). The analysis was based on the ITT population with participants grouped by the treatment assigned at the time of randomization. Participants whose bpCR assessment was missing or invalid were counted as not achieving bpCR. The duration of one treatment cycle was 21 days; the administration of therapy in Cycle 5 did not occur until 2 weeks after surgery. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: At surgery (Cycle 4 Days 22-35)
| Intervention | percentage of participants (Number) |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 41.6 |
| Placebo, Trastuzumab, and Chemotherapy | 22.7 |
Percentage of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) During Cycles 1-4, According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Clinical responses that include percentage of participants with a CR, PR, SD, or PD were determined by investigator during Cycles 1-4 (prior to surgery) on basis of RECIST version 1.1. CR=disappearance of all target lesions i.e., any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeters (mm). PR=at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD=neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum during the study. PD=at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (nadir) with inclusion of baseline. Only participants with measurable disease at baseline were included in the analysis. 1 Cycle=21 days. The percentages have been rounded off to first decimal point. (NCT02586025)
Timeframe: At surgery (Cycle 4 Days 22-35)
| Intervention | percentage of participants (Number) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Missing or Unevaluable |
|---|
| Pertuzumab, Trastuzumab, and Chemotherapy | 11.0 | 77.6 | 8.2 | 0.5 | 2.7 |
,| Placebo, Trastuzumab, and Chemotherapy | 10.0 | 68.2 | 19.1 | 1.8 | 0.9 |
Phase 1b/2 RP2D: DCR in Cohorts 1 to 6
DCR is is defined as the percentage of participants who have a best response of PR, CR, or SD to therapy in accordance with RECIST 1.1 criteria. 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, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). 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 SOD since the treatment started (baseline or after). For SD, tthere was no need for confirmation by a subsequent imaging assessment. (NCT02599324)
Timeframe: Maximum time on study (Phase 1b/2 RP2D) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
| Intervention | percentage of participants (Number) |
|---|
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 80.6 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 66.7 |
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 74.4 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 83.0 |
| Cohort 5 (UC): Ibrutinib 840 mg | 48.3 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | 71.4 |
Phase 1b: ORR in Cohorts 1 to 6
ORR is defined as the percentage of participants who have a best response of partial response (PR) or complete response (CR) to therapy in accordance with RECIST 1.1 criteria. 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, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02599324)
Timeframe: Maximum time on study (Phase 1b only) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 34.2 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
| Intervention | percentage of participants (Number) |
|---|
| Cohort 1 (RCC): Ibrutinib 560 mg + Everolimus | 0 |
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 0 |
| Cohort 2 (UC): Ibrutinib 560 mg + Paclitaxel | 50.0 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 20.0 |
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 11.1 |
| Cohort 4 (CRC): Ibrutinib 560 mg + Cetuximab | 12.5 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 0 |
| Cohort 5 (UC): Ibrutinib 840 mg | 12.5 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | 38.5 |
Phase 1b/2 RP2D: ORR in Cohorts 1 and 2
ORR is defined as the percentage of participants who have a best response to therapy of PR or CR in accordance with RECIST 1.1 criteria. 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, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02599324)
Timeframe: Maximum time on study for Cohort 1 (Phase 1b/2 RP2D) was 37.4 months; for Cohort 2 (Phase 1b/2 RP2D) was 44.7 months. (Reverse Kaplan-Meier estimates)
| Intervention | percentage of participants (Number) |
|---|
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 2.8 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 26.3 |
Phase 1b: Apparent Total Clearance at Steady-State (CLss/F) for Ibrutinib in Cohorts 1 to 4
Actual collection times relative to ibrutinib administration were used for the calculation of pharmacokinetic parameters of ibrutinib and PCI-45227. For actual predose collection times that were < 0, these values were set equal to 0. Predose concentrations were applied as 24 hour concentrations in order to calculate steady-state (Cycle 2 Day 1) pharmacokinetic parameters for ibrutinib and PCI-45227. Apparent total CLss/F (Cycle 2 Day 1) was calculated as dose/AUC0-24h. (NCT02599324)
Timeframe: Cycle 2 Day 1: predose, 1 h ± 15 min, 2 h ± 15 min, 4 h ± 15 min, 6 h ± 15 min postdose
| Intervention | L/h (Mean) |
|---|
| Cohort 1 (RCC): Ibrutinib 560 mg + Everolimus | 1103 |
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 622 |
| Cohort 2 (UC): Ibrutinib 560 mg + Paclitaxel | 994 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 1067 |
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 1102 |
| Cohort 4 (CRC): Ibrutinib 560 mg + Cetuximab | 645 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 595 |
Phase 1b/2 RP2D: PFS in Cohorts 3 to 6
PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of PD or date of death from any cause, whichever occurs first, regardless of the use of subsequent anti-cancer treatment. PD was defined in accordance with RECIST 1.1 criteria. (NCT02599324)
Timeframe: Maximum time on study (Phase 1b/2 RP2D) for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
| Intervention | months (Median) |
|---|
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 4.0 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 5.4 |
| Cohort 5 (UC): Ibrutinib 840 mg | 1.6 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | 2.9 |
Phase 1b/2 RP2D: Progression-Free Survival (PFS) as Assessed by Investigator in Cohorts 1 and 2
PFS is defined as the time from the date of first dose of study treatment to the date of first documentation of progressive disease (PD) or date of death from any cause, whichever occurs first, regardless of the use of subsequent anti-cancer treatment. PD was defined in accordance with Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.1. 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), and an absolute increase of ≥ 5 mm, or unequivocal progression of existing non-target lesions or the appearance of new lesions. (NCT02599324)
Timeframe: Maximum time on study for Cohort 1 (Phase 1b/2 RP2D) was 37.4 months; for Cohort 2 (Phase 1b/2 RP2D) was 44.7 months.
| Intervention | months (Median) |
|---|
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 5.6 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 4.1 |
Phase 1b/2 RP2D: Overall Response Rate (ORR) as Assessed by Investigator in Cohorts 3 to 6
ORR is defined as the percentage of participants who have a best response of partial response (PR) or complete response (CR) to therapy in accordance with RECIST 1.1 criteria. 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, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. (NCT02599324)
Timeframe: Maximum time on study (Phase 1b/2 RP2D) for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
| Intervention | percentage of participants (Number) |
|---|
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 17.9 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 14.9 |
| Cohort 5 (UC): Ibrutinib 840 mg | 6.9 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | 35.7 |
Phase 1b/2 RP2D: Overall Survival (OS) in Cohorts 1 to 6
OS is defined as the time from the date of first dose of study treatment to the date of death from any cause. Subjects who were not known to have died at the data extraction will be censored at date last known alive. (NCT02599324)
Timeframe: Maximum time on study (Phase 1b/2 RP2D) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
| Intervention | months (Median) |
|---|
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 21.0 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 8.2 |
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 7.3 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 15.0 |
| Cohort 5 (UC): Ibrutinib 840 mg | 8.2 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | 15.7 |
Phase 1b/2 RP2D: Duration of Response (DOR) in Cohorts 1 to 6
"DOR is defined for confirmed responders (PR or better) as time from the date of initial response (PR or better) to the date of first documentation of PD (according to RECIST 1.1) or death, whichever occurs first, regardless of use of subsequent anti-cancer treatment. Confirmed responders without documentation of PD or death or with unknown status at the data extraction were censored at the last adequate post-baseline disease assessment showing no evidence of PD. 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.~Per protocol, participants in Phase 1b receiving the Phase 2 RP2D and participants in Phase 2 RP2D were analyzed together." (NCT02599324)
Timeframe: Maximum time on study (Phase 1b/2 RP2D) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 23.5 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months. (Reverse Kaplan-Meier estimates)
| Intervention | months (Median) |
|---|
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 3.1 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 4.4 |
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 5.5 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 11.1 |
| Cohort 5 (UC): Ibrutinib 840 mg | 3.5 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | NA |
Phase 1b: Disease Control Rate (DCR) in Cohorts 1 to 6
DCR is is defined as the percentage of participants who have a best response of PR, CR, or stable disease (SD) to therapy in accordance with RECIST 1.1 criteria. 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, if relevant. All lymph nodes must be non-pathological in size (< 10 mm short axis). 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 SOD since the treatment started (baseline or after). For SD, tthere was no need for confirmation by a subsequent imaging assessment. (NCT02599324)
Timeframe: Maximum time on study (Phase 1b only) for Cohort 1 was 37.4 months; for Cohort 2 was 44.7 months; for Cohort 3 was 41.9 months; for Cohort 4 was 34.2 months; for Cohort 5 was 17.3 months; for Cohort 6 was 20.1 months.
| Intervention | percentage of participants (Number) |
|---|
| Cohort 1 (RCC): Ibrutinib 560 mg + Everolimus | 66.7 |
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 71.4 |
| Cohort 2 (UC): Ibrutinib 560 mg + Paclitaxel | 75.0 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 50.0 |
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 77.8 |
| Cohort 4 (CRC): Ibrutinib 560 mg + Cetuximab | 75.0 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 80.0 |
| Cohort 5 (UC): Ibrutinib 840 mg | 37.5 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | 76.9 |
Phase 1b: Number of Participants With Dose-Limiting Toxicities (DLTs) in Cohorts 1 to 6
A DLT was defined as any Grade 3 (severe) or higher non-hematologic or Grade 4 (life-threatening) hematologic adverse event (AE) occurring during the DLT observation period that was considered to be at least possibly related to the study treatment (ibrutinib or drug combination). (NCT02599324)
Timeframe: 21 days after the initiation of therapy at the start of Cycle 1
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1 (RCC): Ibrutinib 560 mg + Everolimus | 0 |
| Cohort 1 (RCC): Ibrutinib 840 mg + Everolimus | 1 |
| Cohort 2 (UC): Ibrutinib 560 mg + Paclitaxel | 0 |
| Cohort 2 (UC): Ibrutinib 840 mg + Paclitaxel | 0 |
| Cohort 3 (GA): Ibrutinib 560 mg + Docetaxel | 2 |
| Cohort 4 (CRC): Ibrutinib 560 mg + Cetuximab | 0 |
| Cohort 4 (CRC): Ibrutinib 840 mg + Cetuximab | 0 |
| Cohort 5 (UC): Ibrutinib 840 mg | 0 |
| Cohort 6 (UC): Ibrutinib 560 mg + Pembrolizumab | 0 |
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for ITT Population
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Experimental: Alectinib | 1.4 |
| Active Comparator: Premetrexed/Docetaxel | 1.4 |
TTD in Composite of Three Symptoms (Cough, Dyspnea, and Chest Pain) Using EORTC QLQ-LC13 Score for C-ITT Population
TTD for a composite of three symptoms (cough, dyspnea, chest pain) in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for any component of the composite of the three following symptoms [cough, dyspnea [multi-item subscales QLQ-LC13] and chest pain]) as measured by the EORTC QLQ-LC13. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Experimental: Alectinib | 2.8 |
| Active Comparator: Premetrexed/Docetaxel | 1.4 |
Time to CNS Progression in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
"Time to CNS progression was defined as the time from randomization until radiographic evidence of CNS progression. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.~This outcome measure assessment was part of the primary analysis and was not repeated during final analysis." (NCT02604342)
Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
| Intervention | months (Median) |
|---|
| Experimental: Alectinib | NA |
| Active Comparator: Premetrexed/Docetaxel | 1.6 |
Progression-Free Survival (PFS) Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator
PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeter (mm) and the appearance of new lesions. (NCT02604342)
Timeframe: Randomization to first documented disease progression, death from any cause, or study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Experimental: Alectinib | 10.9 |
| Active Comparator: Premetrexed/Docetaxel | 1.4 |
Plasma Concentration of Alectinib
(NCT02604342)
Timeframe: Predose (2 hours) at Baseline, Week 3 and Week 6
| Intervention | nanogram/milliliter (ng/mL) (Geometric Mean) |
|---|
| Experimental: Alectinib | 559 |
PFS Using RECIST Version 1.1 as Assessed by IRC
"PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.~This outcome measure was assessed as part of the primary analysis and was not repeated during final analysis." (NCT02604342)
Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
| Intervention | months (Median) |
|---|
| Experimental: Alectinib | 7.1 |
| Active Comparator: Premetrexed/Docetaxel | 1.6 |
Percentage of Participants With ORR in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and 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 of diameters. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Alectinib | 48.1 |
| Active Comparator: Premetrexed/Docetaxel | 0.0 |
Percentage of Participants With Disease Control in C-ITT Population Using RECIST Version 1.1 as Assessed by IRC
Disease Control Rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and 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 of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started. (NCT02604342)
Timeframe: From first documented CR, PR, or SD lasting at least 5 weeks through study end (up to 33 months)
| Intervention | percentage of participants (Number) |
|---|
| Experimental: Alectinib | 82.7 |
| Active Comparator: Premetrexed/Docetaxel | 25.0 |
Percentage of Participants With Adverse Events (AEs)
An adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Experimental: Alectinib | 89.6 |
| Active Comparator: Premetrexed/Docetaxel | 89.2 |
Duration of Response for Lesions in the CNS (C-DOR) Using RECIST Version 1.1 as Assessed by IRC
DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. C-DOR was defined in a similar way for lesions in the CNS, taking into account all lesions in the body. DOR was evaluated for participants who had a BOR of CR or PR. (NCT02604342)
Timeframe: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Experimental: Alectinib | 13.9 |
| Active Comparator: Premetrexed/Docetaxel | NA |
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. (NCT02604342)
Timeframe: Baseline through Week 60
| Intervention | percentage of participants (Number) |
|---|
| Treatment - Week 0 | Treatment - Week 3 | Treatment - Week 6 | Treatment - Week 12 | Treatment - Week 18 | Treatment - Week 24 | Treatment - Week 30 | Treatment - Week 36 | Treatment - Week 42 | Treatment - Week 48 |
|---|
| Active Comparator: Premetrexed/Docetaxel | 82.9 | 78.8 | 58.6 | 80 | 66.7 | 100 | 66.7 | 50 | 50 | 0 |
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Coughing score | Dyspnoea score | Pain in chest score | Pain in arm or shoulder score |
|---|
| Active Comparator: Premetrexed/Docetaxel | 16.6 | 3.3 | NA | 1.9 |
,| Experimental: Alectinib | 18.1 | 4.1 | NA | 12.5 |
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. (NCT02604342)
Timeframe: Baseline through Week 138
| Intervention | percentage of participants (Number) |
|---|
| Baseline | Treatment - Week 3 | Treatment - Week 6 | Treatment - Week 12 | Treatment - Week 18 | Treatment - Week 24 | Treatment - Week 30 | Treatment - Week 36 | Treatment - Week 42 | Treatment - Week 48 | Treatment - Week 54 | Treatment - Week 60 | Treatment - Week 66 | Treatment - Week 72 |
|---|
| Active Comparator: Premetrexed/Docetaxel | 85.0 | 83.3 | 60.0 | 80.0 | 50.0 | 100 | 66.7 | 66.7 | 66.7 | 100 | 100 | 100 | 100 | 100 |
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Dyspnoea score | Fatigue score |
|---|
| Active Comparator: Premetrexed/Docetaxel | 8.3 | 1.2 |
,| Experimental: Alectinib | 13.3 | 5.6 |
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC30 Score for C-ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-C30. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Dyspnoea score | Fatigue score |
|---|
| Active Comparator: Premetrexed/Docetaxel | 8.3 | 1.0 |
,| Experimental: Alectinib | 16.6 | 14.4 |
Time to Deterioration (TTD) in Lung Cancer Symptoms Using EORTC QLQ-LC13 Score for C-ITT Population
TTD in the overall population is defined as time from randomization to the earliest time with a ≥10-point increase from baseline for symptoms domains (or decrease for functioning domains from baseline for cough, dyspnea [single item and multi-item scales] chest pain [single item], pain in arm/shoulder and fatigue as measured by the EORTC QLQ-LC13. (NCT02604342)
Timeframe: Baseline through study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Coughing score | Dyspnoea score | Pain in chest score | Pain in arm or shoulder score |
|---|
| Active Comparator: Premetrexed/Docetaxel | 16.6 | 1.4 | NA | 1.7 |
,| Experimental: Alectinib | NA | 9.7 | NA | 11.1 |
Overall Survival (OS)
Overall survival (OS) was defined as the time from randomization to death from any cause. OS was confounded by cross-over of participants to the alectinib arm. (NCT02604342)
Timeframe: Randomization to death from any cause, through study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Experimental: Alectinib | 27.8 |
| Active Comparator: Premetrexed/Docetaxel | NA |
PFS in C-ITT Population Using RECIST Version 1.1 as Assessed by Investigator and IRC
"PFS was defined as the time from randomization to the first documented disease progression, as determined using RECIST v1.1, or death from any cause, whichever occurred first. As per RECIST v1.1, disease progression is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm and the appearance of new lesions.~This outcome measure assessment was part of the primary analysis and was not repeated during final analysis." (NCT02604342)
Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
| Intervention | months (Median) |
|---|
| Assessed by Investigator | Assessed by IRC |
|---|
| Active Comparator: Premetrexed/Docetaxel | 1.4 | 1.5 |
,| Experimental: Alectinib | 9.7 | 8.1 |
Percentage of Participants With Objective Response of CR or PR Using RECIST Version 1.1 as Assessed by Investigator and IRC
"ORR was defined as the percentage of participants who attained CR or PR. As per RECIST v1.1, CR: Disappearance of all target lesions and 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 of diameters.~The IRC assessment was part of the primary analysis and was not repeated during final analysis." (NCT02604342)
Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
| Intervention | percentage of participants (Number) |
|---|
| Assessed by Investigator | Assessed by IRC |
|---|
| Active Comparator: Premetrexed/Docetaxel | 2.5 | 11.4 |
,| Experimental: Alectinib | 50.6 | 36.1 |
Percentage of Participants With Disease Control Using RECIST Version 1.1 as Assessed by Investigator and IRC
"Disease control rate (DCR) was defined as the percentage of participants who attained CR, PR, or stable disease (SD) of at least 5 weeks. As per RECIST v1.1, CR: Disappearance of all target lesions and 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 of diameters, SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters since the treatment started.~The IRC assessment was part of the primary analysis and was not repeated during final analysis." (NCT02604342)
Timeframe: Approximately 15 months (Tumor assessments at baseline, every 6 weeks until progressive disease (PD), death or withdrawal from study prior to PD)
| Intervention | percentage of participants (Number) |
|---|
| Assessed by Investigator | Assessed by IRC |
|---|
| Active Comparator: Premetrexed/Docetaxel | 25.0 | 48.6 |
,| Experimental: Alectinib | 86.1 | 76.4 |
Duration of Response (DOR) Using RECIST Version 1.1 as Assessed by Investigator and IRC
"DOR was defined as the time from when response (CR or PR) was first documented to first documented disease progression or death, whichever occurred first. DOR was evaluated for participants who had a best overall response (BOR) of CR or PR.~The IRC assessment was part of the primary analysis and was not repeated during final analysis." (NCT02604342)
Timeframe: From the first documented CR or PR to the first documented disease progression, death, or study end (up to 33 months)
| Intervention | months (Median) |
|---|
| Assessed by Investigator | Assessed by IRC |
|---|
| Active Comparator: Premetrexed/Docetaxel | 2.7 | NA |
,| Experimental: Alectinib | 12.0 | 9.7 |
Compliance of European Quality of Life (EuroQoL) 5 Dimension 5 Levels (EQ-5D-5L) Questionnaire Over Time
Percentage of participants who filled out an ED-5D-5L questionnaire at a visit. EQ-5D-5L: A generic preference-based health utility measure that provides a single index value for health status. The instrument consists of two parts. The first part, health-state classification, contains five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. (NCT02604342)
Timeframe: Baseline through Week 60
| Intervention | percentage of participants (Number) |
|---|
| Treatment - Week 0 | Treatment - Week 3 | Treatment - Week 6 | Treatment - Week 12 | Treatment - Week 18 | Treatment - Week 24 | Treatment - Week 30 | Treatment - Week 36 | Treatment - Week 42 | Treatment - Week 48 | Treatment - Week 54 | Treatment - Week 60 |
|---|
| Experimental: Alectinib | 88.9 | 86.6 | 91.9 | 86.8 | 72.1 | 82.4 | 80 | 80 | 91.7 | 62.5 | 100 | 50 |
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. (NCT02604342)
Timeframe: Baseline through Week 138
| Intervention | percentage of participants (Number) |
|---|
| Baseline | Treatment - Week 3 | Treatment - Week 6 | Treatment - Week 12 | Treatment - Week 18 | Treatment - Week 24 | Treatment - Week 30 | Treatment - Week 36 | Treatment - Week 42 | Treatment - Week 48 | Treatment - Week 54 | Treatment - Week 60 | Treatment - Week 66 | Treatment - Week 72 | Treatment - Week 78 | Treatment - Week 84 | Treatment - Week 90 | Treatment - Week 96 | Treatment - Week 102 | Treatment - Week 108 | Treatment - Week 114 | Treatment - Week 120 | Treatment - Week 126 | Treatment - Week 132 | Treatment - Week 138 |
|---|
| Experimental: Alectinib | 92.4 | 96.1 | 97.2 | 95.5 | 88.5 | 91.1 | 96.2 | 87.8 | 95.3 | 100 | 97.1 | 100 | 89.7 | 88.9 | 84.6 | 78.3 | 88.9 | 100 | 84.6 | 100 | 83.3 | 80.0 | 100 | 100 | 100 |
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer-13 (EORTC QLQ-LC13) Over Time
Percentage of participants who filled out an EORTC QLQ-LC13 questionnaire at a visit. The EORTC QLQ-LC13 module generated one multiple-item scale score assessing dyspnea and a series of single item scores assessing chest pain, arm/shoulder pain, pain in other parts, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. (NCT02604342)
Timeframe: Baseline through Week 138
| Intervention | percentage of participants (Number) |
|---|
| Baseline | Treatment - Week 3 | Treatment - Week 6 | Treatment - Week 12 | Treatment - Week 18 | Treatment - Week 24 | Treatment - Week 30 | Treatment - Week 36 | Treatment - Week 42 | Treatment - Week 48 | Treatment - Week 54 | Treatment - Week 60 | Treatment - Week 66 | Treatment - Week 72 |
|---|
| Active Comparator: Premetrexed/Docetaxel | 82.5 | 83.3 | 63.3 | 80.0 | 50.0 | 100 | 66.7 | 66.7 | 66.7 | 100 | 100 | 100 | 100 | 100 |
Compliance of European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (EORTC QLQ-C30) Over Time
Percentage of participants who filled out an EORTC QLQ-C30 questionnaire at a visit. The EORTC QLQ-C30 questionnaire consisted of 30 questions generating five functional scores (physical, role, cognitive, emotional, and social); a global health status/global quality of life scale score; three symptom scale scores (fatigue, pain, and nausea and vomiting); and six stand alone one-item scores that capture additional symptoms (dyspnea, appetite loss, sleep disturbance, constipation, and diarrhea) and perceived financial burden. (NCT02604342)
Timeframe: Baseline through Week 138
| Intervention | percentage of participants (Number) |
|---|
| Baseline | Treatment - Week 3 | Treatment - Week 6 | Treatment - Week 12 | Treatment - Week 18 | Treatment - Week 24 | Treatment - Week 30 | Treatment - Week 36 | Treatment - Week 42 | Treatment - Week 48 | Treatment - Week 54 | Treatment - Week 60 | Treatment - Week 66 | Treatment - Week 72 | Treatment - Week 78 | Treatment - Week 84 | Treatment - Week 90 | Treatment - Week 96 | Treatment - Week 102 | Treatment - Week 108 | Treatment - Week 114 | Treatment - Week 120 | Treatment - Week 126 | Treatment - Week 132 | Treatment - Week 138 |
|---|
| Experimental: Alectinib | 92.4 | 96.1 | 97.2 | 95.5 | 88.5 | 91.1 | 96.2 | 89.8 | 95.3 | 100 | 97.1 | 100 | 89.7 | 88.9 | 84.6 | 78.3 | 88.9 | 93.8 | 84.6 | 100 | 83.3 | 100 | 100 | 100 | 100 |
Percentage of Participants Who Discontinue Study Treatment 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 percentage of participants that discontinued study treatment due to an AE was reported for each treatment arm. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm. (NCT02611960)
Timeframe: Up to approximately 72 months
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 8.6 |
| Standard Treatment | 15.2 |
Duration of Response (DOR) Per RECIST 1.1
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 as assessed by BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death due to any cause, 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 was reported for each treatment arm. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 12.0 |
| Standard Treatment | 13.1 |
Percentage of Participants Who Experience One or More Adverse Events (AEs)
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 percentage of participants that experienced at least one AE was reported for each treatment arm. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm. (NCT02611960)
Timeframe: Up to approximately 73 months
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 97.4 |
| Standard Treatment | 97.3 |
Percentage of Participants Surviving (OS Rate) at 24 Months
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 known contact. The percentage of participants surviving (OS rate) at 24 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: 24 months
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 40.2 |
| Standard Treatment | 32.2 |
Percentage of Participants With PFS (PFS Rate) 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 occurs earlier. 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. The percentage of participants with PFS (PFS rate) at 12 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: 12 months
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 18.7 |
| Standard Treatment | 30.8 |
Percentage of Participants With PFS (PFS Rate) 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 occurs earlier. 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. The percentage of participants with PFS (PFS rate) at 6 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: 6 months
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 36.3 |
| Standard Treatment | 43.9 |
Progression-free Survival (PFS) Per 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) per RECIST 1.1 based on blinded independent central review (BICR), or death due to any cause, whichever occurs earlier. 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. PFS was reported for each treatment arm. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 4.1 |
| Standard Treatment | 5.5 |
Objective Response Rate (ORR) Per RECIST 1.1
ORR was defined as the percentage of participants in the analysis population who had a confirmed 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. ORR was reported for each treatment arm. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 21.4 |
| Standard Treatment | 23.3 |
Overall Survival (OS)
Overall Survival 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 known contact. OS was reported for each treatment arm. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: Up to approximately 53 months (through analysis cut-off date of 30-Nov-2020)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 17.2 |
| Standard Treatment | 15.3 |
Percentage of Participants Surviving (OS Rate) at 12 Months
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 known contact. The percentage of participants surviving (OS rate) at 12 months is reported for each treatment arm based on the product-limit (Kaplan-Meier) method for censored data. Per protocol, analysis for this outcome measure was performed for the first pembrolizumab course and for the standard treatment arm, with a protocol-specified analysis data cut-off date of 30-Nov-2020. (NCT02611960)
Timeframe: 12 months
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 58.1 |
| Standard Treatment | 57.4 |
Overall Survival Rate
OS was defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS was censored on the last date the subject was known to be alive. Rates provided are Kaplan-Meier estimates. (NCT02613507)
Timeframe: From first dose to the date of death or date participant was last known to be alive (assessed from December 2015 to Oct 2017 approximately 22 months)
| Intervention | percentage (Number) |
|---|
| Rate at 6 months | Rate at 12 months |
|---|
| Docetaxel | 64.8 | 38.8 |
,| Nivolumab | 72.4 | 49.7 |
Overall Survival in Subpopulations
OS was defined as the time between the date of randomization and the date of death. For subjects without documentation of death, OS was censored on the last date the subject was known to be alive. Test stratified by histology (SQ vs NSQ), PD-L1 status at 1%expression level (positive vs negative/unevaluable). (NCT02613507)
Timeframe: From randomization to the date of death or date participant was last known to be alive (assessed from December 2015 to Oct 2017 approximately 22 months)
| Intervention | Months (Median) |
|---|
| Subj. w/ greater than/equal to 1% PDL1 expression | Subj. w/ less than 1% PDL1 expression | Subj. w/ Non-quantifiable PDL1 Expression | Histologically Squamous | Histologically Non-squamous |
|---|
| Docetaxel | 7.89 | 10.25 | 15.97 | 7.89 | 10.22 |
,| Nivolumab | 12.29 | 11.37 | 16.66 | 12.29 | 11.86 |
Progression Free Survival Rate
Clinical deterioration in the absence of unequivocal evidence of progression (per RECIST 1.1) is not considered progression for purposes of determining PFS. Subjects who die without a reported prior progression will be considered to have progressed on the date of their death. Subjects who did not have disease progression or die will be censored on the date of their last evaluable tumor assessment. Subjects who did not have any on study tumor assessments and did not die will be censored at the randomization date. Subjects who started any subsequent anti-cancer therapy without a prior reported progression will be censored at the last evaluable tumor assessment prior to or on initiation of the subsequent anti-cancer therapy. Six month progression-free survival rate as estimated using the Kaplan-Meier method (NCT02613507)
Timeframe: From the time of randomization to the date of the first documented tumor progression or death due to any cause (assessed from December 2015 to Oct 2017 approximately 22 months)
| Intervention | Percentage (Number) |
|---|
| Nivolumab | 28.9 |
| Docetaxel | 22.7 |
Objective Response Rate
Investigator assessed ORR was defined as the number of subjects whose best objective response (BOR) was a confirmed complete response (CR) or confirmed partial response (PR), as determined by the investigator, divided by the number of randomized subjects (NCT02613507)
Timeframe: From date of first dose up to assessed from December 2015 to Oct 2017 approximately 22 months
| Intervention | Percentage of participants (Number) |
|---|
| Nivolumab | 16.6 |
| Docetaxel | 4.2 |
Progression Free Survival in Participants With G12C KRAS Mutation
"Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed using the same techniques as baseline, as well as absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration." (NCT02642042)
Timeframe: Up to 3 years
| Intervention | months (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 3.3 |
Progression Free Survival in All KRAS Mutant Participants
"Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed using the same techniques as baseline, as well as absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration." (NCT02642042)
Timeframe: Up to 3 years
| Intervention | months (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 4.1 |
Overall Survival in Participants With Non-G12C KRAS Mutation
Time from date of registration to date of death due to any cause. (NCT02642042)
Timeframe: up to 3 years
| Intervention | months (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 12.2 |
Overall Survival in All KRAS Mutants
Time from date of registration to date of death due to any cause. (NCT02642042)
Timeframe: Up to 3 years
| Intervention | months (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 10.9 |
Overall Survival in Participants With G12C KRAS Mutation
Time from date of registration to date of death due to any cause. (NCT02642042)
Timeframe: Up to 3 years
| Intervention | months (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 8.8 |
Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With Non-G12C KRAS Mutation
"Proportion of participants who have a partial or complete response to treatment per RECIST v1.1~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or 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" (NCT02642042)
Timeframe: up to 3 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 0.37 |
Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in Participants With G12C KRAS Mutation
"Proportion of participants who have a partial or complete response to treatment per RECIST v1.1~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or 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" (NCT02642042)
Timeframe: Up to 3 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 0.26 |
Response Rate (Confirmed and Unconfirmed Complete and Partial Responses) in All KRAS Mutant Participants
"Proportion of participants who have a partial or complete response to treatment per RECIST v1.1~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or 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" (NCT02642042)
Timeframe: Up to 3 years
| Intervention | proportion of participants (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 0.33 |
Progression Free Survival in Participants With Non-G12C KRAS Mutation
"Time from date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.~Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed using the same techniques as baseline, as well as absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease; appearance of any new lesion/site; death due to disease without prior documentation of progression and without symptomatic deterioration." (NCT02642042)
Timeframe: Up to 3 years
| Intervention | months (Number) |
|---|
| Treatment (Trametinib, Docetaxel) | 4.1 |
Number of Participants With Febrile Neutropenia (FN) in Cycle 1
FN was defined as an oral temperature > 38.3 degrees Celsius (C) (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L. (NCT02643420)
Timeframe: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
| Intervention | Participants (Count of Participants) |
|---|
| Arm 1: SPI-2012 and TC | 4 |
| Arm 2: Pegfilgrastim and TC | 2 |
Number of Participants With Neutropenic Complications in Cycle 1
Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia. (NCT02643420)
Timeframe: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
| Intervention | Participants (Count of Participants) |
|---|
| Arm 1: SPI-2012 and TC | 8 |
| Arm 2: Pegfilgrastim and TC | 8 |
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
Time to ANC Recovery was defined as the time from chemotherapy administration until ANC increased to ≥1.5×10^9/L after the expected nadir within Cycle 1. Time to ANC recovery was assigned as 0 for participants whose ANC value never dropped below 1.5 x10^9/L. (NCT02643420)
Timeframe: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
| Intervention | days (Mean) |
|---|
| Arm 1: SPI-2012 and TC | 3.24 |
| Arm 2: Pegfilgrastim and TC | 3.49 |
Duration of Severe Neutropenia in Cycle 2, 3 and 4
DSN was defined as the number of days of severe neutropenia (ANC <0.5×10^9 /L) from the first occurrence of an ANC below the threshold in Cycles 2, 3, and 4. (NCT02643420)
Timeframe: Days 1, 4, 7, 10, and 15 in cycles 2, 3, and 4 (each cycle was 21 days)
| Intervention | days (Mean) |
|---|
| Cycle 2 | Cycle 3 | Cycle 4 |
|---|
| Arm 1: SPI-2012 and TC | 0.13 | 0.11 | 0.11 |
,| Arm 2: Pegfilgrastim and TC | 0.09 | 0.08 | 0.09 |
Depth of Absolute Neutrophil Count (ANC) Nadir in Cycle 1
Depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or Pegfilgrastim) in Cycle 1. (NCT02643420)
Timeframe: Day 1 and Days 4, 15 in Cycle 1 (each cycle was 21 days)
| Intervention | 10^9 ANC/L (Mean) |
|---|
| Arm 1: SPI-2012 and TC | 2.56 |
| Arm 2: Pegfilgrastim and TC | 2.53 |
Duration of Severe Neutropenia (DSN) in Cycle 1
DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9/L), after the administration of study drug in Cycle 1. (NCT02643420)
Timeframe: Day 1 and Days 4-15 in Cycle 1 (each cycle was 21 days)
| Intervention | days (Mean) |
|---|
| Arm 1: SPI-2012 and TC | 0.20 |
| Arm 2: Pegfilgrastim and TC | 0.35 |
Relative Dose Intensity (RDI) of TC (Docetaxel + Cyclophosphamide) in Cycles 1 to 4
RDI was defined as the percentage of the planned dose that each participant actually received during the study, expressed as the total dose received, divided by the total dose planned and multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles. (NCT02643420)
Timeframe: Cycles 1 to 4 (each cycle was 21 days)
| Intervention | percentage of planned dose (Mean) |
|---|
| Docetaxel | Cyclophosphamide |
|---|
| Arm 1: SPI-2012 and TC | 99.1 | 99.3 |
,| Arm 2: Pegfilgrastim and TC | 98.1 | 99.0 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE for Treatment Period is defined as adverse event with an onset date on or after the date of study drug administration through the end of treatment. TEAE for follow up is defined as any new onset or ongoing AE at the end of Treatment. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events. (NCT02643420)
Timeframe: From the first dose of TC (Docetaxel + Cyclophosphamide) until 12 months after the last dose of study treatment (up to approximately 34 months)
| Intervention | Participants (Count of Participants) |
|---|
| TEAE | SAE |
|---|
| Arm 1: SPI-2012 and TC - Follow up Period | 95 | 8 |
,| Arm 1: SPI-2012 and TC -Treatment Period | 192 | 36 |
,| Arm 2: Pegfilgrastim and TC - Follow up Period | 83 | 2 |
,| Arm 2: Pegfilgrastim and TC -Treatment Period | 204 | 29 |
Number of Participants With Febrile Neutropenia in Cycles 2, 3, and 4
FN was defined as an oral temperature > 38.3 degrees C (101.0 degrees Fahrenheit [F]) or two consecutive readings of >=38.0 degrees C (100.4 degrees F) for 2 hours and ANC <1.0×10^9/L. (NCT02643420)
Timeframe: Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle was 21 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 2 | Cycle 3 | Cycle 4 |
|---|
| Arm 1: SPI-2012 and TC | 1 | 4 | 2 |
,| Arm 2: Pegfilgrastim and TC | 1 | 1 | 0 |
Antigen Spreading (i.e., a Broader Immune Response) With Greater Associated Response Score Compared to Docetaxel Alone After 19 Weeks
Antigen spreading as measured by antigen spread score. The antigen spreading score denotes the presence of a T-cell (cluster of differentiation(CD8)+ and/or cluster of differentiation 4(CD4+) immune response against 2 tumor associated antigens that were not targeted by PROSTVAC:Mucin 1(MUC-1) & carcinoembryonic antigen(CEA). Antigen-specific T-cell responses were determined using intracellular cytokine staining of 4 established markers (Lysosome-associated membrane proteins h-LAMP1, interferon gamma, interleukin-2& tumor necrosis factor) in both CD4+& CD8+T-cells, giving a total of 8 measures of activation per antigen. Numbers of activation markers per antigen were totaled & multiplied by 1.5 to give higher weighting to T-cell responses to antigens that were not targeted by PROSTVAC;& the scores for both MUC-1 & CEA were totaled per participant, with a possible range of 0-24 (0 is a negative result whereas 1.5-24 are positive results). The higher level of response, the better outcome. (NCT02649855)
Timeframe: After 19 Weeks
| Intervention | Score on a scale (Mean) |
|---|
| Arm A/Sequential Docetaxel Followed by PROSTVAC | 4.31 |
| Arm B/ Combined Docetaxel With PROSTVAC | 5.63 |
| Arm C/ PROSTVAC Prior to Docetaxel | 4.00 |
Number of Participants With T-cell Response to Prostate-specific Antigen (PSA)
PSA-specific immune responses T-cell responses were assessed using nonparametric methods. The value denotes the number of participants with T-cell immune responses towards PSA. The higher level of response, the better outcome. (NCT02649855)
Timeframe: 39 weeks and 1 year
| Intervention | Participants (Count of Participants) |
|---|
| 39 Weeks |
|---|
| Arm B/ Combined Docetaxel With PROSTVAC | 6 |
Number of Participants With Serious and/or 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/or 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. (NCT02649855)
Timeframe: Date treatment consent signed to date off study, approximately 70 months and 4 days for Arm A, 38 months and 28 days for Arm B, and 43 months and 29 days for Arm C.
| Intervention | Participants (Count of Participants) |
|---|
| Arm A/Sequential Docetaxel Followed by PROSTVAC | 22 |
| Arm B/ Combined Docetaxel With PROSTVAC | 20 |
| Arm C/ PROSTVAC Prior to Docetaxel | 27 |
Number of Participants With T-cell Response to Prostate-specific Antigen (PSA)
PSA-specific immune responses T-cell responses were assessed using nonparametric methods. The value denotes the number of participants with T-cell immune responses towards PSA. The higher level of response, the better outcome. (NCT02649855)
Timeframe: 39 weeks and 1 year
| Intervention | Participants (Count of Participants) |
|---|
| 39 Weeks | 1 Year |
|---|
| Arm A/Sequential Docetaxel Followed by PROSTVAC | 7 | 5 |
,| Arm C/ PROSTVAC Prior to Docetaxel | 8 | 13 |
Antigen Specific T-cell Immune Composite Response Scores Between All Arms at 39 Weeks and 1 Year
Response score denotes the presence of a T-cell (cluster of differentiation 8(CD8+) and/or cluster of differentiation 4(CD4+) response against 3 tumor associated antigens: prostate-specific antigen(PSA), mucin 1(MUC-1) and carcinoembryonic antigen(CEA). Antigen-specific T-cell immune responses were determined using intracellular cytokine staining of 4 established markers (Lysosome-associated membrane proteins h-LAMP1, interferon gamma, interleukin-2& tumor necrosis factor in both CD4+ & CD8+T-cells, a total of 8 measures of activation per antigen. The number of activation markers for PSA were totaled for a maximum score of 8. Numbers of activation markers for MUC-1 & CEA were totaled & multiplied by 1.5 to give higher weighting to T-cell responses to antigens that were not targeted by PROSTVAC. The scores for PSA, MUC-1 & CEA were totaled per participant, with a possible range of 0-32 (0 is a negative result whereas 1-32 are positive results). Higher level of response, better outcome. (NCT02649855)
Timeframe: 39 weeks and 1 year
| Intervention | Score on a scale (Mean) |
|---|
| 39 Weeks |
|---|
| Arm B/ Combined Docetaxel With PROSTVAC | 7.29 |
Antigen Specific T-cell Immune Composite Response Scores Between All Arms at 39 Weeks and 1 Year
Response score denotes the presence of a T-cell (cluster of differentiation 8(CD8+) and/or cluster of differentiation 4(CD4+) response against 3 tumor associated antigens: prostate-specific antigen(PSA), mucin 1(MUC-1) and carcinoembryonic antigen(CEA). Antigen-specific T-cell immune responses were determined using intracellular cytokine staining of 4 established markers (Lysosome-associated membrane proteins h-LAMP1, interferon gamma, interleukin-2& tumor necrosis factor in both CD4+ & CD8+T-cells, a total of 8 measures of activation per antigen. The number of activation markers for PSA were totaled for a maximum score of 8. Numbers of activation markers for MUC-1 & CEA were totaled & multiplied by 1.5 to give higher weighting to T-cell responses to antigens that were not targeted by PROSTVAC. The scores for PSA, MUC-1 & CEA were totaled per participant, with a possible range of 0-32 (0 is a negative result whereas 1-32 are positive results). Higher level of response, better outcome. (NCT02649855)
Timeframe: 39 weeks and 1 year
| Intervention | Score on a scale (Mean) |
|---|
| 39 Weeks | 1 Year |
|---|
| Arm A/Sequential Docetaxel Followed by PROSTVAC | 7.03 | 5.25 |
,| Arm C/ PROSTVAC Prior to Docetaxel | 6.91 | 6.44 |
Phase 2: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of Complete Response (CR), Partial Response (PR), and Stable Disease (SD)
DCR is the percentage of participants with a best overall response of CR, PR or SD as defined by RECIST v1.1. CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. SD is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD) for target lesions, no progression of non-target lesions, and no appearance of new lesions. PD is defined as 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. (NCT02659020)
Timeframe: Baseline to Measured Progressive Disease or Start of New Anti-Cancer Therapy (Up To 38 Months)
| Intervention | Percentage of participants (Number) |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 74.1 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) | 72.1 |
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 67.4 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 62.8 |
Phase 1b/2: Population PK: Volume of Distribution at Steady State (Vss) of Olaratumab
The Vss is the sum of central volume of distribution (V1) + peripheral volume of distribution (V2). (NCT02659020)
Timeframe: Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
| Intervention | Liter (Mean) |
|---|
| Olaratumab + Gemcitabine + Docetaxel | 5.14 |
Phase 1b/2: Population PK: Clearance of Olaratumab
Population PK: Clearance of Olaratumab (NCT02659020)
Timeframe: Cycle 1-19: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on days 1, 8
| Intervention | Liter Per Hour (Mean) |
|---|
| Olaratumab + Gemcitabine + Docetaxel | 0.0186 |
Phase 1b/2: PK: Cmax of Gemcitabine
Cmax of Gemcitabine. (NCT02659020)
Timeframe: Day 8 of Cycle 1 (end of infusion, 1, 2, 4, 24 hours post-infusion)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel | 2.79 |
| Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 3.49 |
| Phase 2: Olaratumab + Gemcitabine + Docetaxel | 3.01 |
| Phase 2: Placebo + Gemcitabine + Docetaxel | 2.35 |
Phase 1b/2: PK: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC [0-∞]) of Docetaxel
AUC [0-∞] of Docetaxel. (NCT02659020)
Timeframe: 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
| Intervention | nanograms*hours per milliliter (Geometric Mean) |
|---|
| Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel | 4440 |
| Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 2990 |
Phase 1b: Number of Participants With Dose Limiting Toxicity (DLT)
"A Dose Limiting Toxicity is defined as an Adverse Event (AE) that is likely related to the study medication or combination, and fulfils any one of the following criteria, graded according to the NCI-CTCAE Version 4.0:~Febrile neutropenia with documented Grade ≥3 infection or sepsis~Grade 4 neutropenia lasting 7 days or longer.~Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia complicated by hemorrhage.~Nonhematologic Grade ≥3 toxicity, except for toxicities such as nausea, vomiting, transient electrolyte abnormalities, or diarrhoea that can be controlled with optimal medical management within 48 hours." (NCT02659020)
Timeframe: Cycle 1 (Up To 21 Days)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel | 1 |
| Phase 1b: Cohort 2 - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 4 |
| Phase 1b: Cohort 2 Expansion - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 3 |
"Phase 2: Time to First Worsening of the Brief Pain Inventory Short Form Modified (mBPI-sf) Worst Pain Score"
"The mBPI-sf is a 11-item instrument used as a multiple-item measure of cancer pain intensity ranging from 0 (no pain or does not interfere) and ranged through 10 (pain as bad as you can imagine or completely interferes). Time to first worsening of the mBPI-sf worst pain score (TWP) was defined as the time from the date of randomization to the first date of either a worst pain score increase of greater than or equal to (≥) 2 points from baseline or an analgesic drug class increase of ≥1 level. If the patient has not worsened by either of these criteria, TWP was censored for analysis on the last date the mBPI-sf was administered." (NCT02659020)
Timeframe: Baseline to Follow-up (Up To 24 Months)
| Intervention | Months (Median) |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 3.61 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) | 2.27 |
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 3.15 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 2.20 |
Phase 1b/2: PK: Cmax of Docetaxel
Cmax of Docetaxel. (NCT02659020)
Timeframe: 5 min, 1, 3, 24, 48 h post-dose on Cycle 1 Day 8
| Intervention | Nanograms per milliliter (Geometric Mean) |
|---|
| Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel | 903 |
| Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 1110 |
| Phase 2: Olaratumab + Gemcitabine + Docetaxel | 1030 |
| Phase 2: Placebo + Gemcitabine + Docetaxel | 827 |
Phase 2: Time to First Worsening of Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) - Symptom Scales.
The EORTC QLQ-C30 is a self-reported general cancer instrument consisting of 30 items covered by 1 of 3 dimensions: global health status/quality of life (2 items), functional scales (15 total items addressing either physical, role, emotional, cognitive, or social functioning), symptom scales (13 total items addressing either fatigue, nausea/vomiting, pain, dyspnoea, insomnia, appetite loss, constipation, diarrhoea, or financial impact). Time to first worsening of Symptom Burden was defined as the time from randomization to the first observation of worsening on symptom scales (i.e.,) increase of at least 10 points from baseline. For symptom scales, a linear transformation was used to obtain total score ranging from 0 to 100, a high score represents a high level of symptomatology or problems. (NCT02659020)
Timeframe: Baseline to Follow-up (Up to 33 months)
| Intervention | Months (Median) |
|---|
| Fatigue | Nausea and vomiting | Pain | Dyspnoea | Insomnia | Appetite loss | Constipation | Diarrhoea | Financial difficulties |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 0.85 | 3.98 | 2.43 | 2.33 | 1.91 | 1.41 | 4.63 | 3.55 | 7.29 |
,| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 0.95 | 3.78 | 4.67 | 2.14 | 5.32 | 1.12 | 3.25 | 1.41 | NA |
,| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 0.76 | 13.17 | 3.06 | 2.79 | 5.09 | 1.97 | 3.81 | 3.52 | NA |
,| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) | 0.95 | 2.46 | 0.99 | 2.14 | 4.24 | 2.56 | 2.86 | 1.81 | 7.66 |
Phase 2: Health Status on the EuroQol 5-Dimension 5 Level (EQ-5D-5L)
The EQ-5D-5L is a standardized instrument for use as a measure of self-reported health status. Five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) of health status are each assessed with 5 response options (1=no problem, 2=slight, 3=moderate, 4=severe, and 5=extreme problem) and scored as a composite index which were anchored on a scale of 0 to 1 with a higher score representing better health status. Additionally, current health status was assessed on a visual analogue scale (VAS) ranging from 0 to 100 with a higher score representing better health status. (NCT02659020)
Timeframe: Cycle 1 (Day 1), Follow-up (Up to 38 Months)
| Intervention | score on a scale (Mean) |
|---|
| EQ-5D-5L - Index Value [Cycle 1 (Day 1)] | EQ-5D-5L - VAS Score [Cycle 1 (Day 1)] | EQ-5D-5L - Index Value [Follow-up (Up to 38 Months)] | EQ-5D-5L - VAS Score [Follow-up (Up to 38 Months)] |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 0.83 | 76.2 | 0.80 | 74.8 |
,| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 0.80 | 73.5 | 0.74 | 68.7 |
,| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 0.83 | 70.3 | 0.76 | 70.8 |
,| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) | 0.81 | 72.7 | 0.71 | 63.0 |
Phase 1b: PK: Minimum Serum Concentration (Cmin) of Olaratumab
Cmin of Olaratumab. (NCT02659020)
Timeframe: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1
| Intervention | μg/mL (Geometric Mean) |
|---|
| Cycle 1 (Day 1) | Cycle 1 (Day 8) | Cycle 3 (Day 1) |
|---|
| Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel | 95.9 | 64.3 | 137 |
,| Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 142 | 93.3 | 252 |
Phase 1b: PK: Elimination Half-Life (T1/2) of Olaratumab
T1/2 of Olaratumab. (NCT02659020)
Timeframe: Pre-dose, 5 min, 1, 4, 4.5, 24, 96, 168, 336 h post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
| Intervention | days (Geometric Mean) |
|---|
| Cycle 1 (Day 1) | Cycle 1 (Day 8) | Cycle 3 (Day 1) | Cycle 3 (Day 8) |
|---|
| Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel | 4.60 | 6.25 | 5.17 | 5.82 |
,| Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 4.29 | 6.62 | 6.36 | 6.39 |
Phase 1b: Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Olaratumab
Cmax of Olaratumab. (NCT02659020)
Timeframe: Pre-dose, 5 minutes (min), 1, 4, 4.5, 24, 96, 168, 336 hours (h) post-dose on Cycle 1 Day 1, Cycle 1 Day 8, Cycle 3 Day 1, Cycle 3 Day 8
| Intervention | micrograms per milliliter (μg/mL) (Geometric Mean) |
|---|
| Cycle 1 (Day 1) | Cycle 1 (Day 8) | Cycle 3 (Day 1) | Cycle 3 (Day 8) |
|---|
| Phase 1b: Cohort 1 - 15 mg/kg Olaratumab + Gemcitabine + Docetaxel | 432 | 460 | 523 | 513 |
,| Phase 1b: Cohort 2 Overall - 20 mg/kg Olaratumab + Gemcitabine + Docetaxel | 572 | 697 | 644 | 689 |
Phase 2: Progression Free Survival (PFS)
PFS was defined as the time from randomization to the first date of radiologic disease progression (as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 [RECIST v.1.1]) or death due to any cause. Progressive disease (PD) was defined as 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. Participants who have neither progressed nor died were censored at the day of their last radiographic tumor assessment, if available, or date of randomization if no post-baseline radiographic assessment is available. (NCT02659020)
Timeframe: Baseline to Objective Disease Progression or Death from Any Cause (Up To 38 Months)
| Intervention | Months (Median) |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 7.62 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) | 4.37 |
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 5.45 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 4.17 |
Phase 2: Percentage of Participants With a Complete or Partial Response (Objective Response Rate [ORR])
ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. 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. (NCT02659020)
Timeframe: Baseline to Objective Disease Progression or Start of New Anti-Cancer Therapy (Up To 38 Months)
| Intervention | Percentage of participants (Number) |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 32.1 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) | 23.3 |
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 30.4 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 14 |
Phase 2: Overall Survival (OS) (Olaratumab-Naive)
OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact. (NCT02659020)
Timeframe: Baseline to Date of Death Due to Any Cause (Up To 38 Months)
| Intervention | Months (Median) |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 16.76 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab-naive) | 18.04 |
Phase 2: Overall Survival (Olaratumab Pre-Treated)
OS was defined as the time from the date of randomization to the date of death from any cause. For each participant who is not known to have died as of the data-inclusion cut-off date for a particular analysis, overall survival duration was censored for that analysis at the date of last prior contact. (NCT02659020)
Timeframe: Baseline to Date of Death Due to Any Cause (Up To 38 Months)
| Intervention | Months (Median) |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 19.84 |
| Phase 2: Placebo + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 17.31 |
Phase 2: Number of Participants With Treatment Emergent Anti-Olaratumab Antibodies
Number of Participants with Treatment Emergent Anti-Olaratumab Antibodies (NCT02659020)
Timeframe: Baseline through Follow-Up (Up to 38 Months)
| Intervention | Participants (Count of Participants) |
|---|
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab-naive) | 0 |
| Phase 2: Olaratumab + Gemcitabine + Docetaxel (Olaratumab Pre-treated) | 0 |
Number of Participants With Dose-limiting Toxicity (DLT) During the First Treatment Cycle
"Number of participants with DLT occurring during the first treatment cycle. DLT was defined as any of the following adverse events related to nintedanib:~Non-haematological drug-related Common Terminology Criteria for AEs (CTCAE) grade 3 or greater~diarrhoea CTCAE grade 2 for >7 days despite supportive care~nausea CTCAE grade 3 or greater despite supportive care~vomiting CTCAE grade 2 or greater despite supportive care~increase in Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) to CTCAE grade 3 or greater~A increase in ALT and/or AST to CTCAE grade 2 or greater in conjunction with~total bilirubin increase of CTCAE grade 1 or greater~Platelets <50 000/mm3 with bleeding (CTCAE ≥3)~neutropenia of any grade or duration accompanied by fever >38.5°C~neutropenia grade 4 without fever of >7 days duration~Inability to resume nintedanib dosing within 21 days after stopping due to toxicity." (NCT02668393)
Timeframe: First treatment cycle, the first 28 days following the start of trial medication.
| Intervention | Participants (Count of Participants) |
|---|
| 150 mg Nintedanib + Docetaxel | 1 |
| 200 mg Nintedanib + Docetaxel | 1 |
Maximum Tolerated Dose (MTD) of Nintedanib Administered in Combination With Docetaxel
Maximum tolerated dose (MTD) of nintedanib administered in combination with docetaxel. The MTD was defined as the highest dose combination studied for which the incidence of DLTs was no more than 1 out of 6 subjects experiencing a DLT during the first treatment cycle i.e. the incidence of DLTs was no more than 17%. In case dose escalation reached dose level 3 (200 mg bid nintedanib administered without interruption on days of docetaxel infusion) and no more than 1 out of 6 subjects experienced a DLT during the first 28-day cycle at this dose level, dose level 3 was considered the MTD. (NCT02668393)
Timeframe: First treatment cycle, the first 28 days following the start of trial medication.
| Intervention | milligram (Number) |
|---|
| Nintedanib + Docetaxel | NA |
PSA Response in the Standard Treatment Arm and Experimental Treatment Arm
"PSA response measured according to Prostate Cancer Working Group 2 (PCWG2).~The study was terminated after only 9 patients enrolled, 5 to the standard of care docetaxel/prednisone arm and 4 to experimental docetaxel/prednisone/enzalutamide arm." (NCT02685267)
Timeframe: Baseline, Day 84 (C4D1), Day 147 (C7D1), Day 210 (C10D1), Day 231, and every 21 days through study completion (an average of 1 year)
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel/Prednisone | 2 |
| Docetaxel/Prednisone + Enzalutamide | 3 |
Progression-free Survival (Radiographic or Per PCWG2 Criteria)
The primary endpoint of the study is progression-free survival (PFS), defined as the time from randomization to disease progression. Progression will be evaluated using a combination of RECIST and Prostate Cancer Working Group 2 guidelines. (NCT02685267)
Timeframe: 1 year
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel/Prednisone | 0 |
| Docetaxel/Prednisone + Enzalutamide | 0 |
Overall Survival
(NCT02685267)
Timeframe: At both 1 year and 2 years from treatment start
| Intervention | Participants (Count of Participants) |
|---|
| Docetaxel/Prednisone | 2 |
| Docetaxel/Prednisone + Enzalutamide | 4 |
Time to Prostate-specific Antigen Recurrence
To investigate the time from an undetectable prostate-specific antigen (≤0.2 ng/mL) until the prostate-specific antigen is >0.2 over two time-points. (NCT02716974)
Timeframe: 3 years
| Intervention | Months (Median) |
|---|
| Chemohormonal and Definitive Therapy | 31 |
Safety of the Multimodality Therapy as Assessed by Number of Participants With Neutropenia and Surgical or Radiation Toxicities
"To assess the safety and therapeutic benefit of multimodality therapy in men presenting with newly diagnosed oligometastatic prostate cancer (<5 sites of metastases). Safety is defined as the incidence of Grades 3 and 4 neutropenia and surgical- or radiation-induced toxicities.~Neutropenia is a lower than normal number of neutrophils (a type of white blood cell) in the blood. Although dependent on the specific laboratory, the normal number is of neutrophils is generally about 1500-7800 cells/microliter. Grade 3 and 4 neutropenia refer to neutrophil levels <1,000-500 and <500, respectively. The average risk of docetaxel-induced Grade 3 and 4 neutropenia is about 35%. During the course of the study, if we had seen evidence that the risk of Grade 3 and 4 neutropenia was >50%, the study would have been stopped." (NCT02716974)
Timeframe: 3 years
| Intervention | Participants (Count of Participants) |
|---|
| Chemohormonal and Definitive Therapy | 26 |
Efficacy as Assessed by 2-year PSA Progression-free Survival Rate
To evaluate efficacy of multimodality therapy in men, defined as the 2 year PSA progression-free (PSA<0.2 ng/ml) survival among men who have non-castrate testosterone levels 2 years after enrollment. Number of participants (who have non-castrate testosterone levels 2 years after enrollment) with PSA progression-free survival. (NCT02716974)
Timeframe: 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Chemohormonal and Definitive Therapy | 17 |
Overall Response Rate
Overall response rate will be measured (NCT02718820)
Timeframe: 1 year
| Intervention | percentage (Mean) |
|---|
| Docetaxel Plus Pembrolizumab | 22.7 |
Progression-Free Survival (PFS) According to RECIST
Tumor response was assessed by RECIST during the study. Disease progression or PD was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. PFS was defined as the time from start of treatment to the first event of death or PD. Participants without event at the time of analysis were censored at the latest date of last tumor assessment or last date in drug log. The median duration of PFS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months. (NCT02748213)
Timeframe: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
| Intervention | months (Median) |
|---|
| Herceptin + Taxotere + Xeloda | 17.9 |
| Herceptin + Taxotere | 12.8 |
Overall Survival (OS)
OS was defined as the time from start of treatment to date of death for any reason. Participants who were alive at the time of analysis were censored at the latest date of last tumor assessment, last drug intake, or last follow-up information. The median duration of OS and corresponding 95% CI were estimated by Kaplan-Meier analysis and expressed in months. (NCT02748213)
Timeframe: Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall)
| Intervention | months (Median) |
|---|
| Herceptin + Taxotere + Xeloda | 43.5 |
| Herceptin + Taxotere | 47.3 |
Percentage of Participants With Death or Disease Progression According to RECIST
Tumor response was assessed by RECIST during the study. Disease progression or progressive disease (PD) was defined as ≥20% increase in sum LD in reference to the smallest on-treatment sum LD, or the appearance of new lesions. The percentage of participants who died or experienced PD was reported. (NCT02748213)
Timeframe: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin + Taxotere + Xeloda | 67.9 |
| Herceptin + Taxotere | 77.3 |
Percentage of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST)
Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as greater than or equal to (≥) 30 percent (%) decrease in sum of longest diameter (LD) of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. The percentage of participants with a best overall response for CR or PR was reported. The exact 95% confidence interval (CI) for one-sample binomial was determined using the Pearson-Clopper method. (NCT02748213)
Timeframe: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin + Taxotere + Xeloda | 70.5 |
| Herceptin + Taxotere | 72.7 |
Duration of Response (DOR) According to RECIST
Tumor response was assessed by RECIST during the study. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels. PR was defined as ≥30% decrease in sum LD of target lesions in reference to Baseline sum LD. Response was to be confirmed ≥4 weeks after the initial assessment of CR or PR. DOR was defined as the time from first assessment of CR or PR until the first occurrence of documented PD, death, or withdrawal. The median DOR was reported and expressed in months. (NCT02748213)
Timeframe: Tumor assessments at Baseline, then every 6 weeks until Cycle 8 (cycle length of 21 days), then every 12 weeks until progressive disease and/or one year after enrollment; thereafter according to routine clinical practice (up to 66 months overall)
| Intervention | months (Median) |
|---|
| Herceptin + Taxotere + Xeloda | 15.9 |
| Herceptin + Taxotere | 13.4 |
Percentage of Participants Who Died
The percentage of participants who died from any cause was reported. (NCT02748213)
Timeframe: Continuously during treatment (up to 66 months) and at any time after treatment discontinuation until 18 months after last participant enrolled (up to 66 months overall)
| Intervention | percentage of participants (Number) |
|---|
| Herceptin + Taxotere + Xeloda | 35.7 |
| Herceptin + Taxotere | 41.8 |
Investigator-assessed Progression-free Survival
"Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration, or death due to any cause.~Note: The docetaxel arm was closed early due to removal of docetaxel as standard of care treatment. The analyses has been restricted to participants randomized to both arms before the docetaxel arm closed." (NCT02766335)
Timeframe: Up to 3 years post registration
| Intervention | months (Median) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 3.1 |
| Arm II (Docetaxel - Closed to Accrual 4/2015) | 2.8 |
Overall Survival
"Duration from date of sub-study registration (or date of screening/pre-screening registration if participant never enrolls in a sub-study) to date of death due to any cause.~Note: The docetaxel arm was closed early due to removal of docetaxel as standard of care treatment. The analyses has been restricted to participants randomized to both arms before the docetaxel arm closed." (NCT02766335)
Timeframe: Up to 3 years post registration
| Intervention | months (Median) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 12.1 |
| Arm II (Docetaxel - Closed to Accrual 4/2015) | 7.7 |
Response Rate
"The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with MEDI4736 or docetaxel per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).~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~Note: The docetaxel arm was closed early due to removal of docetaxel as standard of care treatment. The analyses has been restricted to participants randomized to both arms before the docetaxel arm closed." (NCT02766335)
Timeframe: Up to 3 years post registration
| Intervention | percentage of participants (Number) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 18.8 |
| Arm II (Docetaxel - Closed to Accrual 4/2015) | 6.7 |
Overall Survival in PD-L1 Positive MEDI4736-treated Participants
Duration from date of sub-study registration (or date of screening/pre-screening registration if patient never enrolls in a sub-study) to date of death due to any cause. (NCT02766335)
Timeframe: up to 3 years post registration
| Intervention | months (Median) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 10.7 |
Overall Survival in MEDI4736-treated Participants
Duration from date of sub-study registration (or date of screening/pre-screening registration if patient never enrolls in a sub-study) to date of death due to any cause. (NCT02766335)
Timeframe: Up to 3 years post-registration
| Intervention | months (Median) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 11.6 |
Overall Response Rate Among PD-L1 Positive Participants Treated With MEDI4736
"The percentage of PD-L1 positive participants with confirmed and unconfirmed, partial response and complete response to treatment with MEDI4736 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).~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" (NCT02766335)
Timeframe: Up to 3 years post registration
| Intervention | percentage of participants (Number) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 14 |
Response Rate in MEDI4736-treated Participants
"The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with MEDI4736 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).~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" (NCT02766335)
Timeframe: Up to 3 years post registration
| Intervention | percentage of participants (Number) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 16 |
Investigator-assessed Progression-free Survival in Participants Treated With MEDI4736
"Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration, or death due to 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 an absolute increase of >= 0.5cm, or a measurable increase in a non-target lesion, or the appearance of new lesions or death due to disease without prior documentation of progression or symptomatic deterioration." (NCT02766335)
Timeframe: Up to 3 years post registration
| Intervention | months (Median) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 2.9 |
Investigator-assessed Progression-free Survival in PD-L1 Positive Participants Treated With MEDI4736
"Duration from date of sub-study registration to date of first documentation of progression, per RECIST 1.1, assessed by local review or symptomatic deterioration or death due to 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 an absolute increase of >= 0.5cm, or a measurable increase in a non-target lesion, or the appearance of new lesions or death due to disease without prior documentation of progression or symptomatic deterioration." (NCT02766335)
Timeframe: up to 3 years post registration
| Intervention | months (Median) |
|---|
| Arm I (MEDI4736 - Closed to Accrual 12/2015) | 2.3 |
Duration of Response Among Participants Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1
"From date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause among participants who achieve a complete or partial response.~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.~It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02785939)
Timeframe: From date of registration to maximum of 2 years and 10 months or death
| Intervention | months (Mean) |
|---|
| Palbociclib | 10.0 |
Overall Survival With Investigational Therapy
"From date of sub-study registration until death due to any cause.~It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02785939)
Timeframe: From date of registration to maximum of 2 years and 10 months or death
| Intervention | months (Median) |
|---|
| Palbociclib | 7.1 |
Progression-free Survival With Palbociclib.
"From date of sub-study registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.~It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02785939)
Timeframe: From date of registration to maximum of 2 years and 10 months or death
| Intervention | months (Median) |
|---|
| Palbociclib | 1.7 |
Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial)
"The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with palbociclib per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).~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~It was pre-specified that only the palbociclib arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02785939)
Timeframe: From date of registration to progression or treatment discontinuation, up to 2 years and 10 months.
| Intervention | percentage of participants (Number) |
|---|
| Palbociclib | 6 |
Time to Initiation of Subsequent Antineoplastic Therapy - Month
"Time to initiation of subsequent systemic antineoplastic therapy was defined as the time from randomization to the initiation of first subsequent systemic antineoplastic therapy.~Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the initiation of first subsequent systemic antineoplastic therapy up to approximately 59 months
| Intervention | Months (Median) |
|---|
| Darolutamide (BAY1841788) + Docetaxel | NA |
| Placebo + Docetaxel | 25.3 |
OS From Date of Randomization Until Death From Any Cause - Number of Events
"Overall survival (OS) was defined as the time from the date of randomization until death from any cause.~Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study." (NCT02799602)
Timeframe: From randomization of the first subject until death from any cause up to the time 533 OS events were reached (approximately 59 months)
| Intervention | Participants (Number) |
|---|
| Number of patients with event | Number of patients censored |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 229 | 422 |
,| Placebo + Docetaxel | 304 | 350 |
Time to Pain Progression - Month
"Time to pain progression was defined as the time from randomization to the first date a patient experienced pain progression.~Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an pain progression event up to approximately 59 months
| Intervention | Months (Median) |
|---|
| Darolutamide (BAY1841788) + Docetaxel | NA |
| Placebo + Docetaxel | 27.5 |
Time to Castration-Resistant Prostate Cancer (CRPC) - Number of Events
"Time to castration-resistant prostate cancer was defined as the time from randomization to the first occurrence of one of the following events: PSA progression, Radiological progression by bone lesions, or Radiological progression by soft tissue and visceral lesions.~Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an CRPC event up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Number of patients with event | Number of patients censored |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 225 | 426 |
,| Placebo + Docetaxel | 391 | 263 |
Time to Initiation of Opioid Use for ≥7 Consecutive Days - Number of Events
"Time to the initiation of opioid use for ≥7 consecutive days was defined as the time fromrandomization to the date of the first opioid use for ≥7 consecutive days. Data of opioid use related to cancer pain was included in the analysis, and opioid use for non-malignant causes was excluded.~Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data." (NCT02799602)
Timeframe: From randomization of the first subject to the first opioid use for ≥7 consecutive days up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Number of patients with event | Number of patients censored |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 92 | 559 |
,| Placebo + Docetaxel | 117 | 537 |
Symptomatic Skeletal Event Free Survival (SSE-FS) - Month
"Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first.~Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an SSE event or death from any cause, whichever occurred first up to approximately 59 months
| Intervention | Months (Median) |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 51.2 |
| Placebo + Docetaxel | 39.7 |
Time to First Symptomatic Skeletal Event (SSE) - Number of Events
"Time to the first SSE was defined as the time from randomization to the first occurrence of an SSE. Identical to the definition used for SSE-FS. Death was not considered as an event in this endpoint.~Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data." (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an SSE event up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Number (%) of patients with event | Number (%) of patients censored |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 95 | 556 |
,| Placebo + Docetaxel | 108 | 546 |
Time to Initiation of Subsequent Antineoplastic Therapy - Number of Events
"Time to initiation of subsequent systemic antineoplastic therapy was defined as the time from randomization to the initiation of first subsequent systemic antineoplastic therapy.~Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the initiation of first subsequent systemic antineoplastic therapy up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Number (%) of patients with event | Number (%) of patients censored |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 219 | 432 |
,| Placebo + Docetaxel | 395 | 259 |
Symptomatic Skeletal Event Free Survival (SSE-FS) - Number of Events
"Symptomatic skeletal event-free survival (SSE-FS) was defined as the time from randomization to the first occurrence of an SSE or death from any cause, whichever occurred first.~Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an SSE event or death from any cause, whichever occurred first up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Number of patients with event | Number of patients censored |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 257 | 394 |
,| Placebo + Docetaxel | 329 | 325 |
OS From Date of Randomization Until Death From Any Cause - Months
"Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~Long-term (Survival) follow-up period: After Active follow-up, patients continued to be contacted approximately every 12 weeks by phone. The end of the Survival follow-up period was defined as when the patient died, was lost to follow-up, withdrew consent, or at the end-of-study.~Median, percentile and other 95% CIs were computed using Kaplan-Meier estimates.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject until death from any cause up to the time 533 OS events were reached (approximately 59 months)
| Intervention | Month (Median) |
|---|
| Darolutamide (BAY1841788) + Docetaxel | NA |
| Placebo + Docetaxel | 48.9 |
Time to First Symptomatic Skeletal Event (SSE) - Month
"Time to the first SSE was defined as the time from randomization to the first occurrence of an SSE. Identical to the definition used for SSE-FS. Death was not considered as an event in this endpoint.~Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an SSE event up to approximately 59 months
| Intervention | Months (Median) |
|---|
| Darolutamide (BAY1841788) + Docetaxel | NA |
| Placebo + Docetaxel | NA |
Time to Castration-Resistant Prostate Cancer (CRPC) - Month
"Time to castration-resistant prostate cancer was defined as the time from randomization to the first occurrence of one of the following events: PSA progression, Radiological progression by bone lesions, or Radiological progression by soft tissue and visceral lesions.~Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an CRPC event up to approximately 59 months
| Intervention | Months (Median) |
|---|
| Darolutamide (BAY1841788) + Docetaxel | NA |
| Placebo + Docetaxel | 19.1 |
Time to Initiation of Opioid Use for ≥7 Consecutive Days - Month
"Time to the initiation of opioid use for ≥7 consecutive days was defined as the time fromrandomization to the date of the first opioid use for ≥7 consecutive days. Data of opioid use related to cancer pain was included in the analysis, and opioid use for non-malignant causes was excluded.~Treatment period: until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data.~NA = Value cannot be estimated due to censored data" (NCT02799602)
Timeframe: From randomization of the first subject to the first opioid use for ≥7 consecutive days up to approximately 59 months
| Intervention | Months (Median) |
|---|
| Darolutamide (BAY1841788) + Docetaxel | NA |
| Placebo + Docetaxel | NA |
Time to Pain Progression - Number of Events
"Time to pain progression was defined as the time from randomization to the first date a patient experienced pain progression.~Treatment period: treatment was provided for all patients, twice daily, until disease progression (symptomatic progressive disease, change of systemic antineoplastic therapy), unacceptable toxicity, consent withdrawal, withdrawal at the discretion of the investigator, death, or non-compliance.~Active follow-up visits from the discontinuation of the darolutamide or placebo treatment period for up to 1 year or until the patient could no longer travel to the clinic, died, was lost to follow-up, or withdrew informed consent and actively objected to collection of further data." (NCT02799602)
Timeframe: From randomization of the first subject to the first occurrence of an pain progression event up to approximately 59 months
| Intervention | Participants (Count of Participants) |
|---|
| Number of patients with event | Number of patients censored |
|---|
| Darolutamide (BAY1841788) + Docetaxel | 222 | 429 |
,| Placebo + Docetaxel | 248 | 406 |
Recommended Phase 2 Dose (RP2D) of the L-NMMA and Docetaxel Combination
"Determine the RP2D of the L-NMMA and docetaxel combination based on the occurrence of DLTs during Phase Ib portion of the study.~As patients are accrued, they will start with 7.5 mg/kg of L-NMMA and 75 mg/m2 of docetaxel and their DLTs will be assessed after completion of the first cycle. This will determine the next cohort dose, until at least 4 patients receive the dose with minimal DLTs that won't require dose reduction." (NCT02834403)
Timeframe: The Dose Limiting Toxicities (DLT) assessment window is the duration required for completing one full cycle (through Day 21).
| Intervention | mg/kg (Number) |
|---|
| Phase Ib - Dose Finding - L-NMMA | 20 |
Dose Limiting Toxicities (DLTs) and Other Adverse Events
Describe the DLTs and other adverse events associated with L-NMMA when combined with docetaxel/amlodipine, as assessed by the CTCAE v4.03 Any Grade ≥ 3 Adverse Events (AE) unless there is clear alternative evidence that the AE was not caused by the study treatment. (NCT02834403)
Timeframe: The approximate length of the study from Cycle 1, Day 1 will be approximately seven months (approximately four months of treatment plus three months of follow-up).
| Intervention | Grade ≥ 3 AE (Count of Units) |
|---|
| Constitutional | Peripheral neuropathy | Dermatological | Infectious | Renal | Elevation of AST/ALT | Dehydration | Gastric | Cardiac | Vascular |
|---|
| Experimental: L-NMMA 10 mg/kg and Docetaxel 75 mg/m2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Experimental: L-NMMA 12.5 mg/kg and Docetaxel 75 mg/m2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Experimental: L-NMMA 15 mg/kg and Docetaxel 75 mg/m2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Experimental: L-NMMA 17.5 mg/kg and Docetaxel 100 mg/m2 | 2 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 2 | 1 |
,| Experimental: L-NMMA 20 mg/kg and Docetaxel 100 mg/m2 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
,| Experimental: L-NMMA 7.5 mg/kg and Docetaxel 75 mg/m2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Experimental: Phase II: RP2D Determined in the Phase Ib | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Recommended Phase 2 Dose (RP2D) of the L-NMMA and Docetaxel Combination
"Determine the RP2D of the L-NMMA and docetaxel combination based on the occurrence of DLTs during Phase Ib portion of the study.~As patients are accrued, they will start with 7.5 mg/kg of L-NMMA and 75 mg/m2 of docetaxel and their DLTs will be assessed after completion of the first cycle. This will determine the next cohort dose, until at least 4 patients receive the dose with minimal DLTs that won't require dose reduction." (NCT02834403)
Timeframe: The Dose Limiting Toxicities (DLT) assessment window is the duration required for completing one full cycle (through Day 21).
| Intervention | mg/m^2 (Number) |
|---|
| Phase Ib - Dose Finding - Docetaxel | 100 |
Clinical Benefit Rate
"Primary Outcome Measure for Phase II: Determine the number of participants with complete response, partial response, or stable disease after 6 cycles of L-NMMA combined with taxane chemotherapy (docetaxel, paclitaxel, or nab-paclitaxel)/amlodipine, as assessed by the RECIST 1.1.~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~SD (stable disease) = small changes that do not meet above criteria~Treatment Failure: taken off the study because of adverse events before the first restaging scan after cycle 2" (NCT02834403)
Timeframe: The approximate length of the study from Cycle 1, Day 1 will be approximately seven months (approximately four months of treatment plus three months of follow-up).
| Intervention | Participants (Count of Participants) |
|---|
| Metastatic breast cancer72594113 | Locally advanced breast cancer72594113 |
|---|
| Complete Response | Stable Disease | Progressive Disease | Treatment Failure | Partial Response |
|---|
| Experimental | 0 |
| Experimental | 3 |
| Experimental | 6 |
| Experimental | 2 |
| Experimental | 4 |
| Experimental | 5 |
| Experimental | 1 |
Time to Maximum Plasma Concentration of L-NMMA and Docetaxel
Determine the time to maximum plasma concentration of the L-NMMA and docetaxel combination. (NCT02834403)
Timeframe: Blood samples will be collected predose (10-30 minutes before L-NMMA infusion) on Days 1, 2, and 5 of Cycle 1 and Days 1 and 5 of Cycle 2 for determination of L-NMMA plus docetaxel plasma PK.
| Intervention | Hours (Mean) |
|---|
| Tmax for LNMMA | Tmas for Docetaxel |
|---|
| Experimental: L-NMMA 15 mg/kg and Docetaxel 75 mg/m2 | 2 | 4 |
,| Experimental: L-NMMA 17.5 mg/kg and Docetaxel 100 mg/m2 | 2 | 4 |
Number of Participants Who Experienced an AE That Was Experienced by ≥10% of Participants in Either Arm
"An AE was 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 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 temporally associated with the use of the Sponsor's product was also an AE. Per protocol, MedDRA preferred terms Neoplasm progression, Malignant neoplasm progression and Disease progression not related to the study intervention are excluded. Per protocol, the number of participants who experienced an AE was reported by treatment arm for all participants (TPS ≥1% stratum of PD-L1 expression) as part of the pre-specified safety analysis at study completion (Final AE collection cut-off date of 14-Oct-2022)." (NCT02864394)
Timeframe: Up to approximately 66 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 206 |
| Docetaxel | 187 |
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
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. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥50% stratum of PD-L1 expression. (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 28.1 |
| Docetaxel | 7.1 |
ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
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. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥1% stratum of PD-L1 expression (all participants). (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 20.7 |
| Docetaxel | 5.7 |
OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (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 was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants). (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 12.9 |
| Docetaxel | 10.6 |
PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (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 occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the SOD 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 was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants). (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 3.3 |
| Docetaxel | 3.0 |
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 PD-L1 Positive (TPS ≥50%) Tumors
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 occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters (SOD) 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 was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression. (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 4.0 |
| Docetaxel | 2.5 |
Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors
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 was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression. (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 12.3 |
| Docetaxel | 10.9 |
DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
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. Response duration was calculated using the Kaplan-Meier method for censored data. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants). (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 16.6 |
| Docetaxel | 6.3 |
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
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. The appearance of one or more new lesions was also considered PD. Response duration was calculated using the Kaplan-Meier method for censored data. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression. (NCT02864394)
Timeframe: Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 16.6 |
| Docetaxel | 6.4 |
Number of Participants Who Discontinued Study Treatment 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 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. Per protocol, the number of participants who discontinued study treatment due to an AE was reported by treatment arm for all participants as part of the pre-specified safety analysis at study completion (Final AE collection cut-off date of 14-Oct-2022). (NCT02864394)
Timeframe: Up to approximately 45 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 32 |
| Docetaxel | 24 |
Number of Participants Who Experienced a Grade 3-5 AE
"An AE is 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 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. Per protocol, MedDRA preferred terms Neoplasm progression, Malignant neoplasm progression and Disease progression not related to the study intervention are excluded. Per protocol, the number of participants who experienced an AE was reported by treatment arm for all participants as part of the pre-specified safety analysis at study completion (Final AE collection cut-off date of 14-Oct-2022)." (NCT02864394)
Timeframe: Up to approximately 66 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 86 |
| Docetaxel | 117 |
Number of Participants Who Experienced 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 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. Per protocol, MedDRA preferred terms Neoplasm progression, Malignant neoplasm progression and Disease progression not related to the study intervention are excluded. Per protocol, the number of participants who experienced an AE was reported by treatment arm for all participants as part of the pre-specified safety analysis at study completion (Final AE collection cut-off date of 14-Oct-2022)." (NCT02864394)
Timeframe: Up to approximately 66 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 206 |
| Docetaxel | 187 |
Number of Participants Who Experienced an Adverse Event of Special Interest (AEOSI)
An AEOSI was defined as any AE that is immune-mediated or potentially immune-mediated. An AE is 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 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. Per protocol, the number of participants who experienced an AE was reported by treatment arm for all participants as part of the pre-specified safety analysis at study completion (Final AE collection cut-off date of 14-Oct-2022). (NCT02864394)
Timeframe: Up to approximately 66 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 63 |
| Docetaxel | 12 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1
Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for PFS at 1, 2, and 3 years. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. (NCT02896855)
Timeframe: At 1, 2, and 3 years
| Intervention | estimate of percentage of participants (Number) |
|---|
| 1 Year | 2 Years | 3 Years |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 52.90 | 19.19 | 12.73 |
,| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 66.37 | 37.85 | 29.44 |
Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1
An objective response was defined as a complete response (CR) or partial response (PR), as determined by the investigator using RECIST v1.1. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. Also per RECIST v1.1, stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum on study; PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The same assessment technique must be used throughout the study for evaluating a particular lesion, and the same investigator should assess all tumor responses for each participant. Participants without a post-baseline tumor assessment were considered non-responders. (NCT02896855)
Timeframe: At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
| Intervention | percentage of participants (Number) |
|---|
| Objective Response (CR + PR) | Complete Response (CR) | Partial Response (PR) | Stable Disease (SD) | Progressive Disease (PD) | Missing or Unevaluable |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 69.1 | 8.2 | 60.8 | 20.6 | 4.1 | 6.2 |
,| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 79.0 | 5.7 | 73.3 | 15.2 | 3.8 | 1.9 |
Number of Participants With at Least One Grade ≥3 Adverse Event
Adverse event (AE) severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0 (NCI-CTCAE v4.0); if the AE was not specifically listed, the following grades of severity were used: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening or disabling; and Grade 5 = death. Severe and serious are not synonymous. Severity refers to the intensity of an AE, whereas a serious AE must meet criteria set out in the protocol; both were independently assessed for each AE. AEs reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. (NCT02896855)
Timeframe: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 83 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 90 |
| Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | 1 |
Number of Participants With Symptomatic Left Ventricular Systolic Dysfunction (LVSD), as Determined Using Echocardiography (ECHO) or Multiple-Gated Acquisition (MUGA) Scan
"The number of participants with symptomatic left ventricular systolic dysfunction (LVSD) at any time during the study, as determined using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scan, were summarized by treatment arm. Symptomatic LVSD was evaluated according to NCI CTCAE v4.0 (for heart failure) and the New York Heart Association (NYHA) classification. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks." (NCT02896855)
Timeframe: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 0 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 0 |
| Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | 0 |
Overall Survival
Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate median OS for each treatment arm. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. The results reported here are from the final analysis. At the primary completion date, the median duration of OS had not been reached and OS data was not considered mature due to the few number of events reported. (NCT02896855)
Timeframe: From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
| Intervention | months (Median) |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | NA |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | NA |
Baseline LVEF and Change From Baseline to Maximum On-Treatment Decrease in LVEF at Any Point During the Study
The baseline left ventricular ejection fraction (LVEF) and change from baseline to the maximum on-treatment decrease in LVEF at any point during the study are reported here. LVEF is the measurement of how much blood is being pumped out of the left ventricle of the heart (the main pumping chamber) with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method should have been used throughout the study, to the extent possible. At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. (NCT02896855)
Timeframe: Baseline and every 9 weeks from date of randomization until treatment discontinuation (up to 4 years, 4 months)
| Intervention | percentage points of LVEF (Mean) |
|---|
| Baseline LVEF (value at visit) | Change from Baseline to Max Decrease in LVEF |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 64.23 | -4.88 |
,| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 65.08 | -5.48 |
Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years
Overall survival (OS) was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS (i.e., alive) at 1, 2, and 3 years. Participants who were alive or lost to follow-up at the time of the analysis were censored at the date they were last known to be alive. Participants with no post-baseline information were censored at the time of randomization plus 1 day. At final analysis, the median [range] time on study for Arm A vs. Arm B was 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks. (NCT02896855)
Timeframe: At 1, 2, and 3 Years
| Intervention | estimate of percentage of participants (Number) |
|---|
| 1 Year | 2 Years | 3 Years |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 90.64 | 73.85 | 58.41 |
,| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 93.44 | 78.87 | 70.79 |
Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1
Duration of objective response was defined as the time from the first occurrence of a documented objective response (complete response [CR] or partial response [PR]) to the time of disease progression, as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, CR is defined as the disappearance of all target lesions, and PR is defined as at least a 30% decrease in the sum of diameters of target lesions. The Kaplan-Meier approach was used to estimate median duration of objective response. Data for participants who did not have an event were censored at the time of the last tumor assessment (if no tumor assessments were performed after baseline visit, at randomization plus 1 day). (NCT02896855)
Timeframe: From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)
| Intervention | months (Median) |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 10.4 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 12.4 |
Number of Participants With at Least One Adverse Event Leading to Withdrawal From Any Treatment
Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. (NCT02896855)
Timeframe: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 10 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 15 |
| Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | 0 |
Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day). (NCT02896855)
Timeframe: From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)
| Intervention | months (Median) |
|---|
| Primary Analysis | Final Analysis |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 12.4 | 12.5 |
,| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 14.5 | 16.5 |
Number of Participants With at Least One Adverse Event
The number of participants per treatment arm experiencing at least one adverse event, including all non-serious and serious adverse events, is reported here. Adverse events reported prior to first crossover treatment were included in the Placebo arm, and in the Crossover arm after that date, for participants in Arm A who crossed over from placebo to pertuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks. (NCT02896855)
Timeframe: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 115 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 121 |
| Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | 5 |
Number of Participants With an Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF) Event, as Determined Using ECHO or MUGA Scan
"An asymptomatic decline in LVEF event is reported as an adverse event of ejection fraction decreased and is defined as either of the following: an absolute decrease in LVEF of ≥10 percentage points from baseline to an LVEF of <50%; or an asymptomatic decrease in LVEF requiring treatment or leading to discontinuation of pertuzumab (or placebo) and trastuzumab. At final analysis, the median [range] time on study treatment with placebo or pertuzumab per arm was: Arm A - Placebo: 52.3 [3-207] weeks; Arm B - Pertuzumab: 66.1 [3-225] weeks; Arm A - Crossover to Pertuzumab: 18.1 [12-24] weeks." (NCT02896855)
Timeframe: From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)
| Intervention | Participants (Count of Participants) |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 0 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 2 |
| Arm A: Crossover to Pertuzumab + Trastuzumab + Docetaxel | 0 |
Number of Participants by the LVEF Abnormality Status Categories Over Time, as Determined by the Change From Baseline in LVEF Using ECHO or MUGA Scans
Left ventricular ejection fraction (LVEF) is the measurement of how much blood is being pumped out of the left ventricle of the heart with each contraction. LVEF was calculated using the modified Simpson method and must have been ≥55% at baseline as determined by the local facility before a participant could be enrolled in the study. The investigator decided which method of LVEF assessment (ECHO [preferred] or MUGA scan) would be used for each participant at baseline, and the same method was to be used throughout the study, to the extent possible. The LVEF abnormality status categories, as a change relative to LVEF at baseline, included: Increase or no change in LVEF; Decrease of <10 LVEF points; Absolute LVEF value ≥50% and a decrease of ≥10 LVEF points; and Absolute LVEF value <50% and a decrease of ≥10 LVEF points. The overall worst LVEF value was defined as the lowest post-baseline value up to the end of the study, including unscheduled assessments and the post-treatment period. (NCT02896855)
Timeframe: Baseline, Weeks 9, 18, 27, 36, 45, 54, 63, 72, 81, 90, 99, 108, 117, 126, 135, 144, 153, 162, 171, 180, 189, 198, 207, 216, and 225, Study Drug Discontinuation Visit (up to 4 years, 4 months), and Treatment-Free Follow-Up at 6 months, and 1 and 2 years
| Intervention | Participants (Count of Participants) | Participants (Count of Participants) |
|---|
| Week 971907266 | Week 971907265 | Week 1871907265 | Week 1871907266 | Week 2771907265 | Week 2771907266 | Week 3671907265 | Week 3671907266 | Week 4571907265 | Week 4571907266 | Week 5471907265 | Week 5471907266 | Week 6371907265 | Week 6371907266 | Week 7271907265 | Week 7271907266 | Week 8171907265 | Week 8171907266 | Week 9071907266 | Week 9071907265 | Week 9971907265 | Week 9971907266 | Week 10871907266 | Week 10871907265 | Week 11771907265 | Week 11771907266 | Week 12671907265 | Week 12671907266 | Week 13571907266 | Week 13571907265 | Week 14471907265 | Week 14471907266 | Week 15371907265 | Week 15371907266 | Week 16271907266 | Week 16271907265 | Week 17171907266 | Week 17171907265 | Week 18071907265 | Week 18071907266 | Week 18971907266 | Week 18971907265 | Week 19871907265 | Week 19871907266 | Week 20771907265 | Week 20771907266 | Week 21671907266 | Week 21671907265 | Week 22571907266 | Study Drug Discontinuation Visit71907265 | Study Drug Discontinuation Visit71907266 | Treatment-Free Follow-Up at 6 Months71907265 | Treatment-Free Follow-Up at 6 Months71907266 | Treatment-Free Follow-Up at 1 Year71907265 | Treatment-Free Follow-Up at 1 Year71907266 | Treatment-Free Follow-Up at 2 Years71907265 | Treatment-Free Follow-Up at 2 Years71907266 | Overall Worst LVEF Value (Maximum LVEF Decrease)71907266 | Overall Worst LVEF Value (Maximum LVEF Decrease)71907265 |
|---|
| Increase or No Change in LVEF | Absolute Value ≥50% & Decrease ≥10 LVEF Points | Decrease <10 LVEF Points | Absolute Value <50% & Decrease ≥10 LVEF Points |
|---|
| Arm A: Placebo + Trastuzumab + Docetaxel | 57 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 63 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 51 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 52 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 61 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 62 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 33 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 45 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 54 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 51 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 35 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 43 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 46 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 4 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 34 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 36 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 29 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 26 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 38 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 27 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 34 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 30 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 17 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 33 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 26 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 15 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 31 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 19 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 29 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 12 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 24 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 11 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 20 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 21 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 23 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 7 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 1 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 14 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 9 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 6 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 18 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 3 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 12 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 15 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 0 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 17 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 1 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 10 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 4 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 16 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 2 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 8 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 14 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 5 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 6 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 9 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 5 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 45 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 28 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 39 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 8 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 20 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 3 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 13 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 10 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 2 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 21 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 75 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 75 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 16 |
| Arm B: Pertuzumab + Trastuzumab + Docetaxel | 22 |
| Arm A: Placebo + Trastuzumab + Docetaxel | 0 |
Progression-Free Survival (Overall)
Progression-free survival (CNS and peripheral) is defined as the time from the date of randomization to the earliest evidence of documented PD in either the CNS or peripheral (using RANO-BM) or death from any cause. The PD will be determined by both the investigator's and the central imaging facility assessments. The same statistical methods that were used for PFS and PFS-BM will be used for PFS (Overall). Progressive Disease (PD) is defined as at least a 20% increase in the sum of longest diameters of CNS target lesions, taking as reference the smallest sum on study. This included the baseline sum if that was the smallest on study. In addition to the relative increase of 20%, at least 1 lesion had to increase by an absolute value of 5 mm or more to be considered progression. (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | months (Median) |
|---|
| NKTR-102 | 2.1 |
| Treatment of Physician's Choice (TPC) | 1.9 |
Clinical Benefit Rate (CBR)
Clinical Benefit Rate will be defined as the proportion of patients having a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) for at least 4 months (≥ 120 days). CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) is 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 was the smallest on study). Stable Disease (SD) is 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 study. (NCT02915744)
Timeframe: For at least 4 months, with an expected average of 1 year
| Intervention | participants (Number) |
|---|
| # of Patients who achieved Complete Response | # of Patients who achieved Partial Response | # of Patients who have Stable Disease >= 120 days | # of Patients who achieved Clinical Benefit Rate (CBR) |
|---|
| NKTR-102 | 0 | 6 | 17 | 23 |
,| Treatment of Physician's Choice (TPC) | 0 | 6 | 5 | 11 |
Progression-Free Survival (Outside the Central Nervous System)
Progression-Free Survival (PFS) is defined as the time from the date of randomization to the earliest evidence of documented Progressive Disease (PD) or of death from any cause. The date of global deterioration or symptomatic deterioration will not be used as the date of PD. The assessment of PFS outside the CNS will utilize RECIST criteria v1.1. (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | months (Median) |
|---|
| NKTR-102 | 2.8 |
| Treatment of Physician's Choice (TPC) | 1.9 |
Overall Survival (OS) of Patients
To compare Overall Survival (OS) of patients who receive 145 mg/m2 NKTR-102 given once every 21 days (q21d) with OS of patients who receive Treatment of Physician's Choice (TPC). Overall survival is defined as the time from the date of randomization to the date of death from any cause. Patients will be followed until their date of death or until final database closure. Patients who are lost-to-follow-up or are alive at the time of analysis will be censored at the time they were last known to be alive or at the date of event cut-off for OS analysis. (NCT02915744)
Timeframe: Within 3 years from study start
| Intervention | months (Median) |
|---|
| NKTR-102 | 7.8 |
| Treatment of Physician's Choice (TPC) | 7.5 |
Number of Participants With Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3
The number of participants with adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v4.3 (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | Participants (Count of Participants) |
|---|
| NKTR-102 | 90 |
| Treatment of Physician's Choice (TPC) | 76 |
Magnitude of Clinical Benefit Assessed by ESMO-MCBS Derived From Overall Survival
The magnitude of clinical benefit of NKTR-102 is assessed by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) (v1.0). The scale is graded 5, 4, 3, 2, 1, where grades 5 and 4 represent a high level of proven clinical benefit, and grade 1 represents no clinical benefit. To determine the magnitude of clinical benefit when the median OS with the standard of treatment is ≤ 1 year, the score is derived from the Hazard Ratio (HR) of Overall Survival, overall survival gain, and QoL improvement between two treatment arms. Values reported in the data table are Overall Survival values. (NCT02915744)
Timeframe: Through study completion, within 3 years from study start
| Intervention | months (Median) |
|---|
| NKTR-102 | 7.8 |
| Treatment of Physician's Choice (TPC) | 7.5 |
Duration of Response (DoR)
Duration of response (DoR) outside the CNS will be defined as the time from first documented CR or PR until the earliest evidence of disease progression per RECIST v1.1 or death from any cause. CR is defined as disappearance of all target lesions for at least 4 weeks with no new lesions, not use of corticosteroids, and patient was stable or improved clinically. PR is defined as at least a 30% decrease in the sum of longest diameters sustained for at least 4 weeks, no new lesions; stable to decreased corticosteroid dose; stable or improved clinically. Progressive Disease (PD) is 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 was the smallest on study). Stable Disease (SD) is 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 study. (NCT02915744)
Timeframe: Through study completion, an expected average of 1 year
| Intervention | months (Median) |
|---|
| NKTR-102 | 7.4 |
| Treatment of Physician's Choice (TPC) | 3.5 |
Duration of Severe Neutropenia (DSN) in Cycles 2, 3 and 4
DSN was defined as the number of days of severe neutropenia (ANC <0.5×10^9/L) from the first occurrence of ANC below the threshold. (NCT02953340)
Timeframe: Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days)
| Intervention | Days (Mean) |
|---|
| Cycle 2 | Cycle 3 | Cycle 4 |
|---|
| (Arm 1): SPI-2012 and TC | 0.08 | 0.07 | 0.07 |
,| (Arm 2): Pegfilgrastim and TC | 0.09 | 0.07 | 0.08 |
Number of Participants With Clinically Significant Laboratory Abnormalities
The number of participants with clinically significant hematology (including basophils, basophils/leukocytes, eosinophils, eosinophils/leukocytes, hematocrit, hemoglobin, lymphocytes, lymphocytes/leukocytes, monocytes, monocytes/leukocytes, neutrophils, neutrophils/leukocytes, platelets, and white blood cells) and serum chemistry (including alanine aminotransferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], bilirubin, calcium, cholesterol, creatinine, potassium, sodium, and triglycerides) laboratory abnormalities were reported. Clinically significant findings in laboratory parameters were based on investigator's discretion according to Common Technical Criteria for Adverse Events (CTCAE) Version 4.03. (NCT02953340)
Timeframe: Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)
| Intervention | Participants (Count of Participants) |
|---|
| Hematology: Basophils | Hematology: Basophils/Leukocytes | Hematology: Eosinophils | Hematology: Eosinophils/Leukocytes | Hematology: Hematocrit | Hematology: Hemoglobin | Hematology: Lymphocytes | Hematology: Lymphocytes/Leukocytes | Hematology: Monocytes | Hematology: Monocytes/Leukocytes | Hematology: Neutrophils | Hematology: Neutrophils/Leukocytes | Hematology: Platelets | Hematology: White Blood Cells | Chemistry: Alanine aminotransferase | Chemistry: Alkaline phosphatase | Chemistry: Aspartate aminotransferase | Chemistry: Bilirubin | Chemistry: Calcium | Chemistry: Cholesterol | Chemistry: Creatinine | Chemistry: Potassium | Chemistry: Sodium | Chemistry: Triglycerides |
|---|
| (Arm 1): SPI-2012 and TC | 0 | 0 | 0 | 0 | 4 | 6 | 0 | 6 | 0 | 0 | 17 | 12 | 10 | 16 | 2 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
,| (Arm 2): Pegfilgrastim and TC | 0 | 0 | 0 | 0 | 2 | 4 | 0 | 13 | 0 | 0 | 23 | 9 | 2 | 18 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 2 | 0 |
Number of Participants With Febrile Neutropenia in Cycles 2, 3 and 4
FN was defined as an oral temperature >38.3°C (101.0°F) or two consecutive readings of >38.0°C (100.4°F) for 2 hours and ANC <1.0×10^9/L. (NCT02953340)
Timeframe: Days 1, 4, 7, 10, and 15 of Cycles 2, 3, and 4 (each cycle = 21 days)
| Intervention | Participants (Count of Participants) |
|---|
| Cycle 2 | Cycle 3 | Cycle 4 |
|---|
| (Arm 1): SPI-2012 and TC | 0 | 0 | 0 |
,| (Arm 2): Pegfilgrastim and TC | 2 | 0 | 0 |
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), and Death
An adverse event (AE) is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product or study procedure, whether or not considered related to the medicinal product. A TEAE is any AE that occurred from the first dose of study treatment through 12 months after the last dose of study treatment or 35 (±5) days after date of participant early discontinuation. SAE is defined as any AE which meets any of the following criteria: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in a persistent or significant disability/incapacity, results in a congenital anomaly/birth defect, includes important medical events. (NCT02953340)
Timeframe: Up to 4 cycles (each cycle = 21 days) plus a 12-month follow-up from the last dose (up to 15 months)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | SAEs | Death |
|---|
| (Arm 1): SPI-2012 and TC | 115 | 12 | 0 |
,| (Arm 1): SPI-2012 and TC: Follow-up Period | 33 | 2 | 0 |
,| (Arm 2): Pegfilgrastim and TC | 116 | 19 | 1 |
,| Arm 2: Pegfilgrastim and TC: Follow-up Period | 48 | 4 | 0 |
Relative Dose Intensity (RDI) of TC Chemotherapy
RDI was defined as the percentage of the planned dose of TC chemotherapy that each participant actually received during the study, and is expressed as the total dose received, divided by total dose planned multiplied by 100. The planned dose was defined as the dose that would be given if no doses were missed and/or no dose reductions were made for the number of cycles started. The total planned dose was the sum of planned doses over all cycles. (NCT02953340)
Timeframe: Cycles 1, 2, 3 and 4 (each cycle = 21 days)
| Intervention | Percentage of planned dose (Mean) |
|---|
| Docetaxel | Cyclophosphamide |
|---|
| (Arm 1): SPI-2012 and TC | 96.9 | 98.4 |
,| (Arm 2): Pegfilgrastim and TC | 98.4 | 98.8 |
Depth of ANC Nadir in Cycle 1
The depth of ANC Nadir was defined as the lowest ANC value after administration of study drug (SPI-2012 or pegfilgrastim) in Cycle 1. (NCT02953340)
Timeframe: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
| Intervention | 10^9 cells/L (Mean) |
|---|
| (Arm 1): SPI-2012 and TC | 2.67 |
| (Arm 2): Pegfilgrastim and TC | 2.06 |
Duration of Severe Neutropenia (DSN) in Cycle 1
DSN was defined as the number of days of severe neutropenia (absolute neutrophil count [ANC] <0.5×10^9 per liter [L]) from the first occurrence of ANC below the threshold. (NCT02953340)
Timeframe: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
| Intervention | Days (Mean) |
|---|
| (Arm 1): SPI-2012 and TC | 0.31 |
| (Arm 2): Pegfilgrastim and TC | 0.39 |
Number of Participants With Febrile Neutropenia (FN) in Cycle 1
FN was defined as an oral temperature >38.3 degree Celsius (°C) (101.0 degrees Fahrenheit [°F]) or two consecutive readings of >38.0°C (100.4°F) for 2 hours and ANC <1.0×10^9/L. (NCT02953340)
Timeframe: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
| Intervention | Participants (Count of Participants) |
|---|
| (Arm 1): SPI-2012 and TC | 1 |
| (Arm 2): Pegfilgrastim and TC | 4 |
Number of Participants With Neutropenic Complications in Cycle 1
Neutropenic complications refer to hospitalizations due to neutropenic events and/or the use of anti-infectives due to neutropenia. (NCT02953340)
Timeframe: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
| Intervention | Participants (Count of Participants) |
|---|
| (Arm 1): SPI-2012 and TC | 1 |
| (Arm 2): Pegfilgrastim and TC | 5 |
Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1
Time to ANC recovery was defined as the time from chemotherapy administration until the participants ANC increased to >=1.5×10^9/L after the expected nadir. For participants with ANC value >=1.5×10^9/L at all times, time to ANC Recovery was assigned a value of 0. (NCT02953340)
Timeframe: Day 1 and daily on Days 4-15 in Cycle 1 (each cycle = 21 days)
| Intervention | Days (Mean) |
|---|
| (Arm 1): SPI-2012 and TC | 3.49 |
| (Arm 2): Pegfilgrastim and TC | 3.35 |
Objective Response Rate (Confirmed and Unconfirmed, Complete and Partial)
"The percentage of participants with confirmed and unconfirmed, partial response and complete response to treatment with AZD4547 per Response Evaluation Criteria in Solid Tumors Criteria (RECIST 1.1).~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.~It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02965378)
Timeframe: From date of registration to maximum of 2 years and 4 months or death.
| Intervention | percentage of participants (Number) |
|---|
| Arm I - AZD4547 | 7 |
Progression-free Survival
"From date of sub-study registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause.~Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), 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.~It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02965378)
Timeframe: From date of registration to maximum of 2 years and 4 months or death.
| Intervention | months (Median) |
|---|
| Arm I - AZD4547 | 2.7 |
Duration of Response Among Patients Who Achieve a Complete Response or Partial Response by Response Evaluation Criteria in Solid Tumors 1.1
"From date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review, or symptomatic deterioration or death due to any cause among patients who achieve complete or partial response per RECIST v1.1.~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.~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.~It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02965378)
Timeframe: From date of registration to maximum of 2 years and 4 months or death.
| Intervention | months (Mean) |
|---|
| Arm I - AZD4547 | 2.2 |
Overall Survival
"From date of sub-study registration on study until death from any cause. Observations for participants last known to be alive were censored.~It was pre-specified that only the AZD4547 arm would be analyzed due to removal of docetaxel as standard of care treatment" (NCT02965378)
Timeframe: From date of registration to maximum of 2 years and 4 months or death
| Intervention | months (Median) |
|---|
| Arm I - AZD4547 | 7.5 |
PSA Response in Participants With a BRCA or ATM Alteration Combined
Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory. (NCT02975934)
Timeframe: From enrollment to primary completion of study (up to approximately 5 years)
| Intervention | percentage of participants (Number) |
|---|
| Rucaparib | 41.9 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 26.7 |
Duration of Response (DOR) by IRR in Participants With a BRCA or ATM Alteration Combined
DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented. (NCT02975934)
Timeframe: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 7.4 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 7.4 |
Interim Overall Survival in Participants With a BRCA Alteration
Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participant was last known to be alive. (NCT02975934)
Timeframe: From enrollment to primary completion of study (up to approximately 5 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 24.3 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 20.8 |
Interim Overall Survival in Participants With a BRCA or ATM Alteration Combined
Overall survival time is calculated as the time from randomization to death (by any cause) +1 day. Participants who have not died will be censored on the date the participants was last known to be alive. (NCT02975934)
Timeframe: From enrollment to primary completion of study (up to approximately 5 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 23.6 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 20.9 |
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: BPI-SF
Changes in health and pain status from baseline to week 25 using: Brief Pain Inventory-Short Form (BPI-SF) questionnaire (on a scale of 1 to 10, from mild to severe, for pain and pain-interference scores). A decrease indicates less severe pain/interference. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase. (NCT02975934)
Timeframe: From enrollment to up to approximately 25 weeks
| Intervention | units on a scale (Mean) |
|---|
| BPI-SF Pain Score | BPI-SF Interference Score |
|---|
| Abiraterone Acetate or Enzalutamide or Docetaxel | 0.14 | 0.65 |
,| Rucaparib | -0.32 | -0.28 |
Trough Plasma PK (Cmin) of Rucaparib Based on Sparse Sampling
Mean trough PK plasma concentration over time in the safety population with at least one PK sample collected at timepoints week 5, 9, 13 and 17; only Week 5 data presented. (NCT02975934)
Timeframe: From enrollment to week 5 of dosing
| Intervention | ng/mL (Median) |
|---|
| Rucaparib | 1310 |
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA or ATM Alteration Combined
Time to PSA progression is defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later. (NCT02975934)
Timeframe: From enrollment to primary completion of study (up to approximately 5 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 5.7 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 3.6 |
Time to Prostate Specific Antigen (PSA) Progression in Participants With a BRCA Alteration
Time to PSA progression is defined as the time from randomization to the date that a ≥ 25% increase and absolute increase of ≥ 2 ng/mL above the nadir (or baseline value for participants who did not have a decline in PSA) in PSA was measured. The increase must be confirmed by a second consecutive assessment conducted at least 3 weeks later. (NCT02975934)
Timeframe: From enrollment to primary completion of study (up to approximately 5 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 6.6 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 3.8 |
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA or ATM Alteration Combined
"The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).~Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria (Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan)." (NCT02975934)
Timeframe: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 10.2 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 6.4 |
Radiographic Progression-free Survival (rPFS) by IRR in Participants With a BRCA Alteration
"The primary efficacy endpoint for the study is rPFSirr, defined as the time from randomization to the first objective evidence of radiographic progression, or death due to any cause (whichever occurs first).~Radiographic disease progression includes confirmed soft tissue disease progression and confirmed bone disease progression as per modified RECIST Version 1.1 (at least a 20% increase in the sum of the LD of target lesions or appearance of one or more new extra-skeletal lesions and/or unequivocal progression of existing nontarget lesions) or PCWG3 criteria Progression by bone is determined by PCWG3 criteria in which at least two new lesions appearing during the first 12-week flare window followed by 2 additional new lesions in the confirmatory scan appearing after the 12-week flare window, or after the 12-week flare window, at least 2 new lesions relative to the first post-treatment scan confirmed on a subsequent scan)." (NCT02975934)
Timeframe: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 11.2 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 6.4 |
PSA Response in Participants With a BRCA Alteration
Confirmed PSA response is defined as ≥ 50% reduction in PSA from baseline on at least two assessments conducted at least 3 weeks apart. PSA response is calculated for all participants with PSA values at baseline and at least one post-baseline assessment. PSA is assessed by a local laboratory. (NCT02975934)
Timeframe: From enrollment to primary completion of study (up to approximately 5 years)
| Intervention | percentage of participants (Number) |
|---|
| Rucaparib | 54.7 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 26.7 |
Objective Response Rate (ORR) by IRR in Participants With a BRCA or ATM Alteration Combined
"ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).~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. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters." (NCT02975934)
Timeframe: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
| Intervention | Participants (Count of Participants) |
|---|
| Rucaparib | 37 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 9 |
Objective Response Rate (ORR) by IRR in Participants With a BRCA Alteration
"ORR is defined as the percentage of participants with a confirmed best response of Complete response (CR) or Partial Response (PR) in participants with measurable disease at study entry. Modified RECIST Version 1.1 criteria is used to determine ORR (ie, CR or PR by IRR assessment and no progression in bone per PCWG3 by IRR assessment).~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. PR is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters." (NCT02975934)
Timeframe: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
| Intervention | Participants (Count of Participants) |
|---|
| Rucaparib | 37 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 7 |
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: FACT-P
Changes in health and pain status from baseline to week 25 using: Functional Assessment of Cancer Therapy-Prostate questionnaire (FACT-P total score, on a scale of 0 to 156 where a higher score is better quality of life). The greater the decrease in score (ie more negative) from baseline to week 25 the greater the decrease in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) (during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase. (NCT02975934)
Timeframe: From enrollment to up to approximately 25 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Rucaparib | -0.8 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | -3.9 |
Change in Patient-reported Outcome (PRO) in Participants With a BRCA Alteration: EQ-5D-5L
Changes in health and pain status from baseline to week 25 using: EuroQol-5D-5L Visual Analogue Scale (EQ-5D-5L VAS; on a scale from 100 to 0, from best to worst health status). The greater the increase in score (including more negative) from baseline to week 25 the greater the increase in health status. Assessments completed during screening, at study treatment visits (Day 1, Day 15, Day 29, Day 43, Day 57, and every 29 days thereafter) during the Treatment Phase, the Treatment Discontinuation Visit, and during the Follow-up Phase. (NCT02975934)
Timeframe: From enrollment to up to approximately 25 weeks
| Intervention | units on a scale (Least Squares Mean) |
|---|
| Rucaparib | 2.4 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 1.8 |
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA Alteration
Defined as the percentage of participants with a complete response (CR), partial response (PR), and stable disease (SD) according to modified RECIST Version 1.1 with no progression in bone per PCWG3 criteria. (NCT02975934)
Timeframe: From enrollment to 6 months
| Intervention | percentage of participants (Number) |
|---|
| Rucaparib | 63.0 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 22.7 |
Clinical Benefit Rate (CBR) by IRR at 6 Months in Participants With a BRCA or ATM Alteration Combined
Defined as the percentage of participants with a Complete Response (CR), Partial Response (PR), and Stable Disease (SD), according to Modified RECIST Version 1.1 with no progression in bone per PCWG3 Criteria. (NCT02975934)
Timeframe: From enrollment to 6 months
| Intervention | percentage of participants (Number) |
|---|
| Rucaparib | 57.6 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 25.4 |
Duration of Response (DOR) by IRR in Participants With a BRCA Alteration
DOR is defined as the time from the first confirmed response (CR or PR by modified RECIST Version 1.1 in participants with nodal or visceral ± nodal disease) until the first date that Progressive Disease (PD) (using the same criteria) is documented. (NCT02975934)
Timeframe: From enrollment to primary completion of study (Total follow-up was up to approximately 4 years)
| Intervention | months (Median) |
|---|
| Rucaparib | 7.4 |
| Abiraterone Acetate or Enzalutamide or Docetaxel | 7.4 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| Treatment (Docetaxel, Carboplatin) | 2 |
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.
| Intervention | Participants (Count of Participants) |
|---|
| Arm B: Platinum Doublet Chemo | 4 |
| Arm C: Nivo 360 mg + Platinum Doublet Chemo | 43 |
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)
| Intervention | Months (Median) |
|---|
| Arm B: Platinum Doublet Chemo | 20.80 |
| Arm C: Nivo 360 mg + Platinum Doublet Chemo | 31.57 |
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.
| Intervention | Participants (Count of Participants) |
|---|
| Arm B: Platinum Doublet Chemo | 16 |
| Arm C: Nivo 360 mg + Platinum Doublet Chemo | 66 |
Number of Participants With Grade 3 or Grade 4 Adverse Events
Assess toxicity of Nivolumab plus single agent chemotherapy compared with single agent chemotherapy alone. Number of grade 3 and 4 toxicities as defined by the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v4. (NCT03041181)
Timeframe: 6 months
| Intervention | participants (Number) |
|---|
| GR4 Thromboembolic Event | GR3 Adverse Events |
|---|
| Arm A | 0 | 0 |
,| Arm B | 1 | 0 |
Time to Prostate-specific Antigen Recurrence
To investigate the time from an undetectable Prostate-specific antigen (≤0.2 ng/mL) until the Prostate-specific antigen is >0.2 over two time-points. (NCT03043807)
Timeframe: 3 years
| Intervention | Month (Median) |
|---|
| Chemohormonal and Definitive Therapy After Prostatectomy | NA |
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
| Intervention | hour*nanogram per milliliter (hr*ng/mL) (Mean) |
|---|
| Plasma | Whole Blood |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 1446.9 | 59284.0 |
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
| Intervention | nanogram per milliliter (ng/mL) (Mean) |
|---|
| Plasma | Whole blood |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 234.3 | 6862.9 |
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
| Intervention | hour (Median) |
|---|
| Plasma | Whole Blood |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 0.980 | 1.000 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| CR | PR | SD | PD |
|---|
| Part B: Pevonedistat + Docetaxel | 0 | 0 | 0 | 2 |
,| Part B: Pevonedistat + Paclitaxel and Carboplatin | 0 | 0 | 2 | 3 |
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
| Intervention | mcg eq (Mean) |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 25029.45 |
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
| Intervention | mcg eq (Mean) |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 44690.50 |
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
| Intervention | microgram equivalent (mcg eq) (Mean) |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 19661.05 |
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
| Intervention | microgram (mcg) (Mean) |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 1161.47 |
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
| Intervention | percentage of dose (Mean) |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 2.45 |
Part A: Renal Clearance (CLR) for Pevonedistat
(NCT03057366)
Timeframe: Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose
| Intervention | liter per hour (L/hr) (Mean) |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 0.8343 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | SAEs |
|---|
| Part A: [14C]-Pevonedistat 25 mg/m^2 | 4 | 1 |
,| Part B: Pevonedistat + Docetaxel | 2 | 1 |
,| Part B: Pevonedistat + Paclitaxel and Carboplatin | 5 | 2 |
Overall Survival
Overall Survival (OS) is defined as the time from trial treatment start to death due to any cause, or censored at date last known alive. (NCT03093272)
Timeframe: Measured from end of study treatment to death due to any cause; OS measured as 22.4 months
| Intervention | months (Number) |
|---|
| Participant 1 | Participant 2 | Participant 3 | Participant 4 | Participant 5 | Participant 6 | Participant 7 | Participant 8 | Participant 9 |
|---|
| Apalutamide Combined With Docetaxel | 22.4 | 4.2 | 21.2 | 16.8 | 1.8 | 9.0 | 10.1 | 5.9 | 12.2 |
Serum PSA Change From Baseline to 12 Weeks on Treatment
The maximum percent PSA change (rise or fall) from baseline to after 12 weeks on study. For patients who discontinue on or before the 12 week assessment or for whom the 12 week assessment is missing, the last observation prior to the week 12 assessment will be utilized. Patients with no post-baseline PSA data will be excluded from the summary. (NCT03093272)
Timeframe: PSA was measured on Cycle 1 Day 1 (Baseline) and at 12 weeks on treatment.
| Intervention | percent (Median) |
|---|
| Apalutamide Combined With Docetaxel | 13.0 |
Maximum Blood Concentration (Cmax) for Docetaxel Pharmacokinetic Analysis
The pharmacokinetic (PK) parameters of the first 9 patients enrolled at Dana-Farber Cancer Institute will be determined using noncompartmental methods with WinNonLin version 5.2. Maximum blood concentration (Cmax) will be determined by visual inspection. Due to the premature termination of the study, only 9 patients were evaluated. The PK samples were collected on Days 1 and 2 of the first two treatment cycles. (NCT03093272)
Timeframe: Cycle 1, 2: During infusion at pre-dose, 15 minutes and 30 minutes post-dose, end of dose, and 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post dose.
| Intervention | ng/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| Apalutamide Combined With Docetaxel | 2415 | 1641 |
To Evaluate Progression-free Survival on the Combination of Docetaxel Plus Apalutamide
"Progression free survival (PFS) is defined as the time from treatment initiation until the occurrence of one of the following:~A participant was considered to have progressed by bone scan if~the first bone scan with greater than or equal to (≥) 2 new lesions compared to baseline was observed in less than (<) 12 weeks from study drug initiation and was confirmed by a second bone scan taken ≥6 weeks later showing ≥2 additional new lesions (a total of ≥4 new lesions compared to baseline);~the first bone scan with ≥2 new lesions compared to baseline was observed in ≥12 weeks from study drug initiation and the new lesions were verified on the next bone scan ≥6 weeks later (a total of ≥2 new lesions compared to baseline);~Progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) by RECIST v. 1.1; or~Death from any cause." (NCT03093272)
Timeframe: Disease was evaluated radiologically at baseline and every 12 weeks on treatment; PFS follow up was up to 9.4 months
| Intervention | months (Number) |
|---|
| Participant 1 | Participant 2 | Participant 3 | Participant 4 | Participant 5 | Participant 6 | Participant 7 | Participant 8 | Participant 9 |
|---|
| Apalutamide Combined With Docetaxel | 5.6 | NA | 5.6 | 8.1 | 1.8 | 4.8 | 5.1 | NA | 9.4 |
Area Under the Curve (AUC) for Docetaxel Pharmacokinetic Analysis
The area under the blood concentration-time curve (linear trapezoidal rule) will be determined between 0-24 hours (AUC0-24). The PK samples were collected during the first two days of cycles 1 and 2. (NCT03093272)
Timeframe: Cycle 1, 2: During infusion at pre-dose, 15 minutes and 30 minutes post-dose, end of dose, and 0.5, 1, 1.5, 2, 4, 6, 8, 24 hours post dose.
| Intervention | ng•h/mL (Mean) |
|---|
| Cycle 1 | Cycle 2 |
|---|
| Apalutamide Combined With Docetaxel | 3406 | 3095 |
Overall Survival
Overall survival was defined as the time from randomization to death due to any cause. (NCT03150875)
Timeframe: Through database cutoff date of 31-July-2020 (up to approximately 35 months)
| Intervention | Months (Median) |
|---|
| Sintilimab | 11.79 |
| Docetaxel | 8.25 |
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAE)
TEAE is any AE that developed or worsened in severity compared to the baseline during the period from first dose of any study treatment up to 90 days after the last dose of any study treatment. Percentage of participants experiencing TEAE is calculated. (NCT03150875)
Timeframe: Through database cutoff date of 31-July-2020 (up to approximately 35 months)
| Intervention | Percentage of participants (Number) |
|---|
| Sintilimab | 97.20 |
| Docetaxel | 96.20 |
Progression-free Survival by Investigators' Assessment
Progression-free survival (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 Evaluation Criteria in Solid Tumours (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions, or unequivocal progression of non-target lesion. 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 as assessed by investigators per RECIST 1.1 was reported for each arm. (NCT03150875)
Timeframe: Through database cutoff date of 31-July-2020 (up to approximately 35 months)
| Intervention | Months (Median) |
|---|
| Sintilimab | 4.3 |
| Docetaxel | 2.79 |
Overall Response Rate (ORR) Per RECIST v1.1 as Assessed by Investigators
ORR was defined as the percentage of participants in the analysis population who had a confirmed 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. (NCT03150875)
Timeframe: Through database cutoff date of 31-July-2020 (up to approximately 35 months)
| Intervention | Percentage of participants (Number) |
|---|
| Sintilimab | 25.5 |
| Docetaxel | 2.2 |
Duration of Response (DOR) Per RECIST v1.1 as Assessed by Investigators
For participants who demonstrated a 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 or unequivoval progression of non-target lesion. 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. The DOR per RECIST 1.1 for all participants who experienced a CR or PR is presented. (NCT03150875)
Timeframe: Through database cutoff date of 31-July-2020 (up to approximately 35 months)
| Intervention | Months (Median) |
|---|
| Sintilimab | 12.45 |
| Docetaxel | 4.14 |
Disease Control Rate (DCR)
Percentage of patients who achieved complete response, partial response and stable disease. DCR will be calculated from the first day of the first cycle to the date of metastatic or primary tumor relapse, or last contact date, or date of death (if death comes before disease progression), or data cut-off. (NCT03159143)
Timeframe: Up to 4 years
| Intervention | percentage of participants (Median) |
|---|
| Docetaxel and Oxaliplatin | 26.3 |
Overall Survival
The overall survival will be calculated as the number of months from the date of first treatment until death or the cut-off date. (NCT03159143)
Timeframe: Up to 4 years
| Intervention | months (Median) |
|---|
| Docetaxel and Oxaliplatin | 7 |
Response Rate
Percentage of patients who experienced a greater than or equal to a 30% reduction in measurable disease, as per the RECIST criteria. (NCT03159143)
Timeframe: Up to 4 years
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel and Oxaliplatin | 11 |
Time to Progression (TTP)
Time to progression (TTP) will be calculated as number of months from the date of first treatment to the date of disease progression or the date of death (disease-related causes) or the cut-off date. (NCT03159143)
Timeframe: Up to 4 years
| Intervention | months (Median) |
|---|
| Docetaxel and Oxaliplatin | 3 |
Number of Patients With Locoregional Recurrence and Locoregional Progression in the Thyroid Bed or Regional Lymph Nodes
Will be summarized using descriptive statistics. (NCT03211117)
Timeframe: 2.3 years
| Intervention | Participants (Count of Participants) |
|---|
| Cohort B (Pembrolizumab, Chemoradiation) | 0 |
Overall Survival Rate
Defined as the percentage of evaluable patients who are alive at 6 months. (NCT03211117)
Timeframe: At 6 months
| Intervention | percentage of participants alive (Number) |
|---|
| Cohort B (Pembrolizumab, Chemoradiation) | 0 |
Incidence of Adverse Events Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine adverse event patterns. This data is reported in the adverse events section of this report. (NCT03211117)
Timeframe: 2.3 years
| Intervention | Participants (Count of Participants) |
|---|
| Cohort B (Pembrolizumab, Chemoradiation) | 3 |
The Percentage of Patients That Respond to Treatment
"Response is defined as either Partial Response or Complete Response. Partial Response is defined as 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.~Complete Response is defined as the 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." (NCT03228186)
Timeframe: Up to 2 Years
| Intervention | percent of participants (Number) |
|---|
| Pevonedistat Plus Docetaxel | 22 |
The Number of Toxicities by System Organ Class
All recorded toxicities will be listed and tabulated by system organ class. The NCI CTCAE version 4.03 will be utilized for AE reporting. (NCT03228186)
Timeframe: up to 30 days post last study drug dose, patients were allowed to stay on study drug treatment until progression. Data was collected over 3.5 years.
| Intervention | percentage of Grade 3-5 Adverse Events (Number) |
|---|
| Blood and Lymphatic system disorders- grade 3 | Gastrointestinal disorders- grade 3 | General disorders and administration site conditions- grade 3 | hepatobiliary disorders- grade 3 | infections and infestations- grade 3 | infections and infestations- grade 4 | investigations- grade 3 | investigations- grade 4 | metabolism and nutrition disorders- grade 3 | nervous system disorders- grade 3 | respiratory, thoracic and mediastinal disorders- grade 3 | Skin and subcutaneous tissue disorders- grade 3 |
|---|
| Pevonedistat Plus Docetaxel | 10 | 6.7 | 10 | 3.3 | 3.3 | 3.3 | 16.7 | 13.3 | 3.3 | 3.3 | 3.3 | 3.3 |
The Number of Patients Who Achieve Stable Disease
"Stable disease rate will be reported as the count and proportion of patients who achieve stable disease.~Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for Partial Response (PR) nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum LD since the treatment started." (NCT03228186)
Timeframe: Up to 2 Years
| Intervention | Participants (Count of Participants) |
|---|
| Pevonedistat Plus Docetaxel | 12 |
52-week PSA Complete Response (CR) Rate
The 52-week PSA CR rate was defined as the proportion of participants achieving PSA complete response (CR) at 52-weeks (+/- 1 week) from date of enrollment (i.e., initiation of both enzalutamide and docetaxel) of all evaluable participants. PSA CR was defined as PSA level less than 0.2 ng/ml for two consecutive measurements at least three weeks apart (date of initial PSA level 0.2 ng/ml was acknowledged as date of response). In subjects with missed PSA assessments at 52 (+/- 1) weeks, (a) if a confirmed CR was achieved and at least one PSA assessment occurred beyond the 52-week window showed serologic complete response (providing the subject did not earlier experience confirmed progressive disease), the subject achieved 52-week PSA Complete Response and (b) if confirmed CR was achieved before the 52-week window and the first assessment after the 52-week window was not a CR, the subject did not achieve a 52-week PSA Complete Response. (NCT03246347)
Timeframe: 52 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Single Arm | 22 |
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
| Intervention | Participants (Count of Participants) |
|---|
| ddACTHP | 2 |
| TCHP | 5 |
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
| Intervention | Participants (Count of Participants) |
|---|
| ddACTHP | 1 |
| TCHP | 4 |
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
| Intervention | events (Number) |
|---|
| ddACTHP | 2 |
| TCHP | 2 |
Number of Non-cardiac Toxicities
The frequency of adverse events categorized using CTCAE v4.03 (NCT03329378)
Timeframe: 2 years
| Intervention | events (Number) |
|---|
| ddACTHP | 63 |
| TCHP | 120 |
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
| Intervention | Participants (Count of Participants) |
|---|
| ddACTHP | 0 |
| TCHP | 0 |
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
| Intervention | hour*nanogram per milliliter (h*ng/mL) (Geometric Mean) |
|---|
| Pevonedistat 25 mg/m^2 | 1190 |
| Pevonedistat 50 mg/m^2 | 2510 |
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
| Intervention | milliseconds (Least Squares Mean) |
|---|
| Predose | 1 Hour Postdose | 2 Hours Postdose | 3 Hours Postdose | 4 Hours Postdose | 6 Hours Postdose | 9 Hours Postdose | 11 Hours Postdose | 24 Hours Postdose |
|---|
| Pevonedistat 25 mg/m^2 | -2.894 | 1.152 | -0.090 | -1.557 | -3.406 | -4.665 | -4.499 | -3.018 | -5.245 |
,| Pevonedistat 50 mg/m^2 | -1.220 | 3.360 | 1.514 | -0.167 | -1.802 | -4.463 | -3.608 | -2.333 | -6.499 |
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
| Intervention | milliseconds (Least Squares Mean) |
|---|
| Predose | 1 Hour Postdose | 2 Hours Postdose | 3 Hours Postdose | 4 Hours Postdose | 6 Hours Postdose | 9 Hours Postdose | 11 Hours Postdose | 24 Hours Postdose |
|---|
| Pevonedistat 25 mg/m^2 | 2.099 | 3.580 | 1.477 | 3.074 | 3.816 | 2.143 | -1.419 | 0.020 | -1.897 |
,| Pevonedistat 50 mg/m^2 | -1.884 | -0.206 | -0.099 | 1.877 | 1.305 | 0.198 | -2.482 | -5.250 | -3.105 |
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
| Intervention | milliseconds (Least Squares Mean) |
|---|
| Predose | 1 Hour Postdose | 2 Hours Postdose | 3 Hours Postdose | 4 Hours Postdose | 6 Hours Postdose | 9 Hours Postdose | 11 Hours Postdose | 24 Hours Postdose |
|---|
| Pevonedistat 25 mg/m^2 | -0.459 | 1.447 | -0.212 | 0.138 | -1.068 | -0.192 | -0.791 | -0.551 | -0.946 |
,| Pevonedistat 50 mg/m^2 | -0.482 | 0.850 | -0.043 | 0.184 | -0.241 | -0.319 | -0.221 | -0.769 | -0.470 |
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
| Intervention | beats per minute (bpm) (Least Squares Mean) |
|---|
| Predose | 1 Hour Postdose | 2 Hours Postdose | 3 Hours Postdose | 4 Hours Postdose | 6 Hours Postdose | 9 Hours Postdose | 11 Hours Postdose | 24 Hours Postdose |
|---|
| Pevonedistat 25 mg/m^2 | 0.602 | -2.068 | -1.812 | -0.993 | -0.279 | 2.712 | 2.545 | 2.794 | 4.432 |
,| Pevonedistat 50 mg/m^2 | 0.981 | -1.595 | -0.556 | 1.929 | 2.736 | 6.411 | 7.134 | 7.511 | 7.609 |
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
| Intervention | milliseconds (Least Squares Mean) |
|---|
| Predose | 1 Hour Postdose | 2 Hours Postdose | 3 Hours Postdose | 4 Hours Postdose | 6 Hours Postdose | 9 Hours Postdose | 11 Hours Postdose | 24 Hours Postdose |
|---|
| Pevonedistat 25 mg/m^2 | 1.310 | 3.180 | 0.840 | 1.754 | 2.567 | 0.598 | -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 |
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)
| Intervention | percentage of participants (Number) |
|---|
| Part B: Pevonedistat 25 mg/m^2 + Docetaxel | 9.1 |
| Part B: Pevonedistat 20 mg/m^2 + Carboplatin + Paclitaxel | 8.3 |
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
| Intervention | hours (h) (Mean) |
|---|
| Pevonedistat 25 mg/m^2 | 7.21 |
| Pevonedistat 50 mg/m^2 | 6.73 |
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
| Intervention | nanograms per milliliter (ng/mL) (Geometric Mean) |
|---|
| Pevonedistat 25 mg/m^2 | 197 |
| Pevonedistat 50 mg/m^2 | 509 |
Number of Participants With Laboratory Values Change From Baseline
Number of participants changed from baseline in laboratory values of worst toxicity grade (grade 0= wnl, grade 1= mild, grade 2= moderate, grade 3= severe) based on US conventional units by cohort (NCT03338790)
Timeframe: From first dose to up to 30 days post last dose (Up to 34 months)
| Intervention | Participants (Number) |
|---|
| Hemoglobin Grade 0 | Hemoglobin Grade 1 | Hemoglobin Grade 2 | Platelet Grade 0 | Platelet Grade 1 | Leukocytes Grade 0 | Leukocytes Grade 1 | Leukocytes Grade 2 | Lymphocytes Grade 0 | Lymphocytes Grade 1 | Lymphocytes Grade 2 | Lymphocytes Grade 3 | Neutrophil Grade 0 | Neutrophil Grade 1 | Neutrophil Grade 2 | Alkaline Phosphatase Grade 0 | Alkaline Phosphatase Grade 1 | Alkaline Phosphatase Grade 2 | Alkaline Phosphatase Grade 3 | Aspartate Aminotransferase Grade 0 | Aspartate Aminotransferase Grade 1 | Alanine Aminotransferase Grade 0 | Alanine Aminotransferase Grade 1 | Bilirubin Grade 0 | Bilirubin Grade 1 | Creatinine Grade 0 | Creatinine Grade 1 |
|---|
| Arm A1 | 23 | 38 | 8 | 35 | 4 | 38 | 10 | 1 | 24 | 10 | 3 | 1 | 35 | 3 | 1 | 25 | 13 | 9 | 1 | 52 | 5 | 47 | 4 | 4 | 1 | 30 | 7 |
Objective Response Rate Per Prostate Cancer Clinical Trials Working Group 3 (ORR-PCWG3)
Objective response rate per prostate cancer clinical trials working group 3 (ORR-PCWG3) for target lesions and assessed by MRI is the percentage of participants who have a confirmed complete or partial best overall response (BOR) per PCWG3 among treated participants who have measurable disease (NCT03338790)
Timeframe: Up to approximately 36 months
| Intervention | Percentage of participants (Number) |
|---|
| Overall | Homologous Recombination Deficiency (HRD+) |
|---|
| Arm A1 | 10.3 | 17.2 |
,| Arm A2 | 15.4 | 25.0 |
,| Arm B | 40.0 | 36.8 |
,| Arm C | 11.1 | 20.0 |
Number of Participants With Laboratory Abnormalities in Specific Liver Tests
"Number of participants with laboratory abnormalities in specific liver tests based on SI conventional units to assess the overall safety and tolerability of BMS-986213 in combination with chemotherapy vs. Nivolumab in combination with chemotherapy. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized:~ALT or AST > 3 x ULN, > 5 x ULN, > 10 x ULN and > 20 x ULN~Total bilirubin > 2 x ULN~ALP > 1.5 x ULN~Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN~Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 1.5 x ULN~Concurrent (within 1 day) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN~Concurrent (within 30 days) ALT or AST > 3 x ULN and total bilirubin > 2 x ULN" (NCT03338790)
Timeframe: From first dose to up to 30 days post last dose (up to 34 months)
| Intervention | Participants (Number) |
|---|
| ALT or AST > 3xULN | ALT or AST > 5xULN | ALT or AST > 10xULN | ALT or AST > 20xULN | TOTAL BILIRUBIN > 2xULN | ALP > 1.5xULN | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within one day | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 1.5xULN within 30 days | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within one day | Concurrent ALT or AST elevation > 3xULN with total Bilirubin > 2xULN within 30 days |
|---|
| Arm A1 | 19 | 11 | 2 | 0 | 3 | 49 | 3 | 4 | 2 | 2 |
,| Arm A2 | 23 | 14 | 5 | 1 | 1 | 34 | 1 | 1 | 1 | 1 |
,| Arm B | 6 | 3 | 1 | 1 | 1 | 34 | 0 | 0 | 0 | 0 |
,| Arm C | 4 | 3 | 0 | 0 | 0 | 21 | 1 | 1 | 0 | 0 |
Number of Participants With Laboratory Abnormalities in Specific Thyroid Tests
"Number of participants with laboratory abnormalities in specific thyroid tests based on US conventional units. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized:~TSH value > ULN and~with baseline TSH value <= ULN~with at least one FT3/FT4 test value < LLN within 2-week window after the abnormal TSH test~with all FT3/FT4 test values >= LLN within 2-week window after the abnormal TSH test~with FT3/FT4 missing within 2-week window after the abnormal TSH test.~TSH < LLN and~with baseline TSH value >= LLN~with at least one FT3/FT4 test value > ULN within 2-week window after the abnormal TSH test~with all FT3/FT4 test values <= ULN within 2-week window after the abnormal TSH test~with FT3/FT4 missing within 2-week window after the abnormal TSH test" (NCT03338790)
Timeframe: From first dose to up to 30 days post last dose (Up to 34 months)
| Intervention | Participants (Number) |
|---|
| TSH > ULN | TSH > ULN with TSH <= ULN at baseline | TSH > ULN with at least one FT3/FT4 test value < LLN | TSH > ULN with all other FT3/FT4 test values >= LLN | TSH > ULN with FT3/FT4 test missing | TSH < LLN | TSH < LLN with TSH >= LLN at baseline | TSH < LLN with at least one FT3/FT4 test value > ULN | TSH < LLN with all other FT3/FT4 test values <= ULN | TSH < LLN with FT3/FT4 test missing |
|---|
| Arm A1 | 22 | 17 | 10 | 10 | 2 | 16 | 13 | 5 | 8 | 3 |
,| Arm A2 | 17 | 12 | 6 | 9 | 2 | 12 | 11 | 5 | 4 | 3 |
,| Arm B | 12 | 7 | 7 | 3 | 2 | 25 | 19 | 2 | 11 | 12 |
,| Arm C | 17 | 12 | 5 | 10 | 2 | 8 | 8 | 7 | 0 | 1 |
Number of Participants With Laboratory Values Change From Baseline
Number of participants changed from baseline in laboratory values of worst toxicity grade (grade 0= wnl, grade 1= mild, grade 2= moderate, grade 3= severe) based on US conventional units by cohort (NCT03338790)
Timeframe: From first dose to up to 30 days post last dose (Up to 34 months)
| Intervention | Participants (Number) |
|---|
| Hemoglobin Grade 0 | Hemoglobin Grade 1 | Hemoglobin Grade 2 | Platelet Grade 0 | Platelet Grade 1 | Leukocytes Grade 0 | Leukocytes Grade 1 | Lymphocytes Grade 0 | Lymphocytes Grade 1 | Lymphocytes Grade 2 | Neutrophil Grade 0 | Neutrophil Grade 2 | Alkaline Phosphatase Grade 0 | Alkaline Phosphatase Grade 1 | Alkaline Phosphatase Grade 2 | Alkaline Phosphatase Grade 3 | Aspartate Aminotransferase Grade 0 | Aspartate Aminotransferase Grade 1 | Alanine Aminotransferase Grade 0 | Alanine Aminotransferase Grade 1 | Bilirubin Grade 0 | Bilirubin Grade 1 | Creatinine Grade 0 | Creatinine Grade 1 |
|---|
| Arm C | 8 | 12 | 2 | 13 | 0 | 13 | 2 | 14 | 2 | 3 | 7 | 1 | 8 | 6 | 0 | 0 | 9 | 4 | 4 | 1 | 3 | 0 | 3 | 2 |
Number of Participants With Laboratory Values Change From Baseline
Number of participants changed from baseline in laboratory values of worst toxicity grade (grade 0= wnl, grade 1= mild, grade 2= moderate, grade 3= severe) based on US conventional units by cohort (NCT03338790)
Timeframe: From first dose to up to 30 days post last dose (Up to 34 months)
| Intervention | Participants (Number) |
|---|
| Hemoglobin Grade 0 | Hemoglobin Grade 1 | Hemoglobin Grade 2 | Platelet Grade 0 | Platelet Grade 1 | Leukocytes Grade 0 | Leukocytes Grade 1 | Leukocytes Grade 2 | Lymphocytes Grade 0 | Lymphocytes Grade 1 | Lymphocytes Grade 2 | Lymphocytes Grade 3 | Neutrophil Grade 0 | Neutrophil Grade 1 | Alkaline Phosphatase Grade 0 | Alkaline Phosphatase Grade 1 | Alkaline Phosphatase Grade 2 | Alkaline Phosphatase Grade 3 | Aspartate Aminotransferase Grade 0 | Aspartate Aminotransferase Grade 1 | Alanine Aminotransferase Grade 0 | Alanine Aminotransferase Grade 1 | Bilirubin Grade 0 | Creatinine Grade 0 | Creatinine Grade 1 |
|---|
| Arm A2 | 21 | 28 | 3 | 32 | 1 | 34 | 6 | 0 | 30 | 8 | 3 | 0 | 26 | 4 | 33 | 4 | 1 | 3 | 49 | 4 | 48 | 3 | 12 | 30 | 5 |
,| Arm B | 30 | 20 | 2 | 10 | 0 | 28 | 4 | 1 | 28 | 0 | 5 | 0 | 37 | 1 | 13 | 13 | 2 | 0 | 28 | 6 | 13 | 3 | 2 | 13 | 5 |
Number of Participants With Adverse Events (AEs)
Number of Participants with any grade adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, and immune-mediated AEs using the Common Toxicity Criteria Grade for Adverse Events (CTCAE V4) (NCT03338790)
Timeframe: From first dose to up to 30 days post last dose (Up to 34 months)
| Intervention | Participants (Number) |
|---|
| Adverse Events (AEs) | Serious Adverse Events (SAEs) | AEs leading to discontinuation | Immune-mediated AEs (Pneumonitis) | Immune-mediated AEs (Diarrhea/Colitis) | Immune-mediated AEs (Hepatitis) | Immune-mediated AEs (Nephritis/Renal Dysfunction) | Immune-mediated AEs (Rash) | Immune-mediated AEs (Hypersensitivity/Infusion Reactions) |
|---|
| Arm A1 | 88 | 47 | 39 | 1 | 4 | 8 | 2 | 5 | 0 |
,| Arm A2 | 71 | 37 | 26 | 2 | 4 | 7 | 3 | 5 | 1 |
,| Arm B | 83 | 41 | 33 | 8 | 1 | 3 | 0 | 9 | 1 |
,| Arm C | 49 | 20 | 18 | 0 | 0 | 2 | 0 | 10 | 3 |
Number of Deaths
Number of deaths in all treated participants (NCT03338790)
Timeframe: Up to 36 months
| Intervention | Deaths (Number) |
|---|
| Arm A1 | 59 |
| Arm A2 | 42 |
| Arm B | 44 |
| Arm C | 28 |
Prostate-Specific Antigen Response Rate (RR-PSA)
Prostate-specific antigen response rate (RR-PSA) is the percentage of treated participants with a 50% or greater decrease in PSA from baseline to the lowest post-baseline PSA result (NCT03338790)
Timeframe: Up to approximately 36 months
| Intervention | Percentage of participants (Number) |
|---|
| Overall | Homologous Recombination Deficiency (HRD+) |
|---|
| Arm A1 | 11.9 | 18.2 |
,| Arm A2 | 27.3 | 41.9 |
,| Arm B | 46.9 | 50.0 |
,| Arm C | 34.1 | 50.0 |
Duration of Response (DOR) in the PDL-1 Positive Analysis Set.
DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first (NCT03430843)
Timeframe: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
| Intervention | Months (Median) |
|---|
| Tislelizumab | 7.1 |
| Investigator Chosen Chemotherapy | 5.7 |
Duration of Response (DOR) in the ITT Analysis Set
DOR is defined as the time from the first determination of an objective response until the first documentation of progression as assessed by the investigator per RECIST v1.1, or death, whichever comes first (NCT03430843)
Timeframe: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
| Intervention | Months (Median) |
|---|
| Tislelizumab | 7.1 |
| Investigator Chosen Chemotherapy | 4.0 |
HRQoL as Assessed by EORTC QLQ-C30 in the PDL-1 Positive Analysis Set
Mean change from baseline in EORTC QLQ-C30 Index score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer participants. It includes global health status and quality of life questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes (NCT03430843)
Timeframe: Baseline to Cycle 6 (21 days per cycle)
| Intervention | Score on a scale (Mean) |
|---|
| Baseline | Change at Cycle 6 |
|---|
| Investigator Chosen Chemotherapy | 18.8 | 0.5 |
,| Tislelizumab | 16.8 | 0.5 |
HRQoL as Assessed by EORTC QLQ-OES18) in the PDL-1 Positive Analysis Set.
Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes. (NCT03430843)
Timeframe: Baseline to Cycle 6 (21 days per cycle)
| Intervention | Score on a scale (Mean) |
|---|
| Baseline | Change at Cycle 6 |
|---|
| Investigator Chosen Chemotherapy | 18.1 | -2.9 |
,| Tislelizumab | 16.5 | -0.9 |
HRQoL as Assessed by EORTC QLQ-Oesophagus Cancer Module (EORTC QLQ-OES18) Reported in ITT Analysis Set
Mean change from baseline in EORTC QLQ-OES18 index score. The EORTC QLQ-OES18 is a questionnaire that assesses overall symptoms in esophageal cancer participants. It includes questions related to overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Raw scores are transformed into a 0 to 100 scale via linear transformation. A higher score indicates better health outcomes. (NCT03430843)
Timeframe: Baseline to Cycle 6 (21 days per cycle)
| Intervention | Score on a scale (Mean) |
|---|
| Baseline | Change at Cycle 6 |
|---|
| Investigator Chosen Chemotherapy | 16.3 | 3.0 |
,| Tislelizumab | 14.7 | -0.6 |
HRQoL as Assessed by EQ-5D-5L in the PD-L1 Positive Analysis Set
Mean change from baseline in EQ-5D-5L visual acuity score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes. (NCT03430843)
Timeframe: Baseline to Cycle 6 (21 days per cycle)
| Intervention | Score on a scale (Mean) |
|---|
| Baseline | Change at Cycle 6 |
|---|
| Investigator Chosen Chemotherapy | 70.5 | 4.4 |
,| Tislelizumab | 74.1 | -0.5 |
HRQoL as Assessed by European Quality of Life 5-Dimensions 5-Level Questionnaire (EQ-5D-5L) in the ITT Analysis Set
Mean change from baseline in EQ-5D-5L visual acuity score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' A higher score indicates better health outcomes. (NCT03430843)
Timeframe: Baseline to Cycle 6 (21 days per cycle)
| Intervention | Score on a scale (Mean) |
|---|
| Baseline | Change at Cycle 6 |
|---|
| Investigator Chosen Chemotherapy | 72.5 | -5.9 |
,| Tislelizumab | 73.7 | -0.6 |
Number of Participants Experiencing Adverse Events (AEs)
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), which includes laboratory tests, physical exams, electrocardiogram results and vital signs (NCT03430843)
Timeframe: From the first dose date to 30 days after the last dose date; up to approximately 4 years and 11 months
| Intervention | Participants (Number) |
|---|
| Number of participants with TEAEs | Number of participants with SAEs |
|---|
| Investigator Chosen Chemotherapy | 236 | 106 |
,| Tislelizumab | 245 | 109 |
Progression-free Survival (PFS) in the PDL-1 Positive Analysis Set
PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the PDL-1 Positive Analysis Set (NCT03430843)
Timeframe: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
| Intervention | Months (Median) |
|---|
| Tislelizumab | 2.7 |
| Investigator Chosen Chemotherapy | 2.3 |
Progression-free Survival (PFS) in the ITT Analysis Set
PFS is defined as the time from the date of randomization to the date of first documentation of disease progression assessed by the investigator per RECIST v1.1 or death, whichever occurs first; reported for the ITT analysis set (NCT03430843)
Timeframe: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
| Intervention | Months (Median) |
|---|
| Tislelizumab | 1.6 |
| Investigator Chosen Chemotherapy | 2.1 |
Overall Survival (OS) in the PDL-1 Positive Analysis Set
OS is defined as the time from the date of randomization until the date of death due to any cause in the PD-L1 positive population, defined as vCPS ≥10%. (NCT03430843)
Timeframe: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
| Intervention | Months (Median) |
|---|
| Tislelizumab | 10.2 |
| Investigator Chosen Chemotherapy | 5.1 |
Overall Survival (OS) in the Intent-to-Treat (ITT) Analysis Set
OS is defined as the length of time from the date of randomization until the date of death due to any cause in all randomized participants (NCT03430843)
Timeframe: Approximately 2 years and 10 months from date of first randomization
| Intervention | Months (Median) |
|---|
| Tislelizumab | 8.6 |
| Investigator Chosen Chemotherapy | 6.3 |
Overall Response Rate (ORR) in the PD-L1 Positive Analysis Sets
ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per RECIST v1.1; (NCT03430843)
Timeframe: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Tislelizumab | 26.3 |
| Investigator Chosen Chemotherapy | 11.3 |
Objective Response Rate (ORR) in the ITT Analysis Set
ORR is defined as the percentage of participants who had complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1; (NCT03430843)
Timeframe: Through End-of-Trial Analysis data cutoff date of 28-Dec-2022 (up to approximately 5 years)
| Intervention | Percentage of Participants (Number) |
|---|
| Tislelizumab | 20.3 |
| Investigator Chosen Chemotherapy | 9.8 |
Progression-free Survival (PFS) (Cohort 1 Only)
"PFS: defined as time on study to time patients progressed on the drug combination or death or latest follow-up if progression/death is not observed yet~Progressive disease: 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)." (NCT03449901)
Timeframe: Through completion of follow-up (median follow-up 494 days, full range of 5-1500 days).
| Intervention | months (Median) |
|---|
| Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel | 5.0597 |
Safety and Tolerability of Regimen as Measured by Number and Grade of Adverse Events
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 will be utilized for all toxicity reporting. (NCT03449901)
Timeframe: From start of treatment through 30 days after completion of treatment (median treatment of 9 months + 1 month follow-up)
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1-2 anemia | Grade 3-5 anemia | Grade 3-5 febrile neutropenia | Grade 1-2 eosiniphilia | Grade 3-5 mitral valve disease | Grade 1-2 atrial fibrillation | Grade 3-5 atrial fibrillation | Grade 1-2 palpitations | Grade 3-5 pericardial effusion | Grade 1-2 sinus bradycardia | Grade 1-2 sinus tachycardia | Grade 3-5 sinus tachycardia | Grade 1-2 chest pain - cardiac | Grade 1-2 ear pain | Grade 1-2 vertigo | Grade 3-5 tinnitus | Grade 1-2 hyperthyroidism | Grade 1-2 cataract | Grade 1-2 blurred vision | Grade 1-2 watering eyes | Grade 1-2 retinal tear | Grade 1-2 dry eye | Grade 1-2 abdominal distension | Grade 1-2 abdominal pain | Grade 3-5 abdominal pain | Grade 1-2 anal hemorrhage | Grade 1-2 anal mucositis | Grade 1-2 ascites | Grade 3-5 ascites | Grade 1-2 bloating | Grade 1-2 colitis | Grade 1-2 colonic hemorrhage | Grade 3-5 colonic perforation | Grade 1-2 constipation | Grade 1-2 dental caries | Grade 3-5 dental caries | Grade 1-2 diarrhea | Grade 3-5 diarrhea | Grade 1-2 dry mouth | Grade 1-2 dyspepsia | Grade 1-2 dysphagia | Grade 1-2 fecal incontinence | Grade 1-2 flatulence | Grade 1-2 gastroesophageal reflux disease | Grade 1-2 hematochezia | Grade 3-5 generalized GI bleed | Grade 1-2 tooth extraction | Grade 1-2 hemorrhoids | Grade 3-5 lower gastrointestinal hemorrhage | Grade 1-2 lip pain | Grade 1-2 mucositis oral | Grade 1-2 nausea | Grade 1-2 oral pain | Grade 1-2 rectal hemorrhage | Grade 3-5 small intestinal obstruction | Grade 3-5 typhlitis | Grade 3-5 upper gastrointestinal hemorrhage | Grade 1-2 vomiting | Grade 3-5 vomiting | Grade 1-2 chills | Grade 5 death NOS | Grade 1-2 edema face | Grade 1-2 edema limbs | Grade 3-5 edema limbs | Grade 1-2 edema trunk | Grade 3-5 edema trunk | Grade 1-2 facial pain | Grade 1-2 fatigue | Grade 3-5 fatigue | Grade 1-2 fever | Grade 1-2 flu-like symptoms | Grade 1-2 generalized edema | Grade 1-2 infusion related reaction | Grade 1-2 injection site reaction | Grade 1-2 localized edema | Grade 1-2 malaise | Grade 1-2 non-cardiac chest pain | Grade 3-5 non-cardiac chest pain | Grade 1-2 pain at injection site | Grade 1-2 pain | Grade 3-5 hepatic hemorrhage | Grade 1-2 allergic reaction | Grade 3-5 allergic reaction | Grade 3-5 Celiac disease | Grade 1-2 bladder infection | Grade 1-2 bronchial infection | Grade 1-2 enterocolitis infectious | Grade 3-5 enterocolitis infectious | Grade 1-2 eye infection | Grade 1-2 folliculitis | Grade 1-2 gum infection | Grade 3-5 influenza A infection | Grade 1-2 lung infection | Grade 3-5 lung infection | Grade 1-2 papulopustular rash | Grade 1-2 paronychia | Grade 3-5 pleural infection | Grade 3-5 sepsis | Grade 1-2 sinusitis | Grade 1-2 skin infection | Grade 3-5 skin infection | Grade 1-2 thrush | Grade 1-2 tooth infection | Grade 1-2 upper respiratory infection | Grade 3-5 upper respiratory infection | Grade 1-2 urinary tract infection | Grade 3-5 urinary tract infection | Grade 3-5 wound infection | Grade 1-2 ankle fracture | Grade 1-2 bruising | Grade 1-2 fall | Grade 3-5 fall | Grade 1-2 fracture | Grade 1-2 twisted knee | Grade 3-5 ileal bleed due to tumor invasion | Grade 3-5 postoperative hemorrhage | Grade 1-2 spinal fracture | Grade 3-5 wound complication | Grade 1-2 activated partial thromboplastin time prolonged | Grade 3-5 activated partial thromboplastin time prolonged | Grade 1-2 alanine aminotransferase increased | Grade 3-5 alanine aminotransferase increased | Grade 1-2 alkaline phosphatase increased | Grade 3-5 alkaline phosphatase increased | Grade 1-2 aspartate aminotransferase increased | Grade 3-5 aspartate aminotransferase increased | Grade 1-2 blood bilirubin increased | Grade 3-5 blood bilirubin increased | Grade 1-2 lactate dehydrogenase increased | Grade 1-2 cardiac troponin I increased | Grade 3-5 cardiac troponin I increased | Grade 1-2 cardiac troponin T increased | Grade 1-2 creatinine increased | Grade 3-5 creatinine increased | Grade 1-2 electrocardiogram QT corrected interval prolonged | Grade 3-5 electrocardiogram QT corrected interval prolonged | Grade 1-2 INR increased | Grade 3-5 GGT increased | Grade 3-5 INR increased | Grade 3-5 ammonia increased | Grade 1-2 lipase increased | Grade 3-5 lipase increased | Grade 1-2 lymphocyte count decreased | Grade 3-5 lymphocyte count decreased | Grade 1-2 neutrophil count decreased | Grade 3-5 neutrophil count decreased | Grade 1-2 platelet count decreased | Grade 3-5 platelet count decreased | Grade 1-2 weight loss | Grade 1-2 white blood cell count decreased | Grade 3-5 white blood cell count decreased | Grade 3-5 acidosis | Grade 1-2 anorexia | Grade 3-5 anorexia | Grade 1-2 dehydration | Grade 3-5 dehydration | Grade 1-2 hypercalcemia | Grade 1-2 hyperglycemia | Grade 3-5 hyperglycemia | Grade 1-2 hyperkalemia | Grade 3-5 hyperkalemia | Grade 1-2 hyperlipidemia | Grade 1-2 hypermagnesemia | Grade 3-5 hypermagnesemia | Grade 1-2 hypernatremia | Grade 1-2 hyperuricemia | Grade 3-5 hyperuricemia | Grade 1-2 hypoalbuminemia | Grade 3-5 hypoalbuminemia | Grade 1-2 hypocalcemia | Grade 3-5 hypocalcemia | Grade 1-2 hypoglycemia | Grade 3-5 hypoglycemia | Grade 1-2 hypokalemia | Grade 3-5 hypokalemia | Grade 1-2 hyponatremia | Grade 3-5 hyponatremia | Grade 1-2 hypophosphatemia | Grade 3-5 hypophosphatemia | Grade 1-2 arthralgia | Grade 1-2 back pain | Grade 3-5 back pain | Grade 1-2 bone pain | Grade 1-2 flank pain | Grade 1-2 generalized muscle weakness | Grade 1-2 joint effusion | Grade 1-2 muscle cramp | Grade 1-2 muscle weakness lower limb | Grade 1-2 myalgia | Grade 1-2 neck pain | Grade 1-2 pain in extremity | Grade 1-2 palpable lump RUE | Grade 1-2 skin pailloma, R hallux | Grade 3-5 disease progression | Grade 1-2 tumor pain | Grade 3-5 tumor pain | Grade 1-2 concentration impairment | Grade 1-2 dizziness | Grade 1-2 dysgeusia | Grade 1-2 extrapyramidal disorder | Grade 1-2 headache | Grade 1-2 plantar sensitivity | Grade 3-5 cerebral hemorrhage | Grade 1-2 neuralgia | Grade 1-2 paresthesia | Grade 1-2 paresthesia (face) | Grade 1-2 peripheral sensory neuropathy | Grade 1-2 phantom pain | Grade 1-2 presyncope | Grade 3-5 spinal cord compression | Grade 3-5 syncope | Grade 1-2 tremor | Grade 3-5 agitation | Grade 1-2 anxiety | Grade 1-2 confusion | Grade 3-5 confusion | Grade 1-2 depression | Grade 3-5 depression | Grade 1-2 insomnia | Grade 1-2 irritability | Grade 1-2 acute kidney injury | Grade 3-5 acute kidney injury | Grade 1-2 dysuria | Grade 1-2 hematuria | Grade 1-2 proteinuria | Grade 1-2 renal calculi | Grade 1-2 urinary frequency | Grade 1-2 urinary incontinence | Grade 1-2 urinary retention | Grade 3-5 urinary tract obstruction | Grade 1-2 genital edema | Grade 1-2 pelvic pain | Grade 1-2 groin pain | Grade 1-2 vaginal hemorrhage | Grade 1-2 allergic rhinitis | Grade 3-5 bronchial obstruction | Grade 1-2 cough | Grade 1-2 dyspnea | Grade 3-5 dyspnea | Grade 1-2 epistaxis | Grade 1-2 hoarseness | Grade 1-2 hypoxia | Grade 3-5 hypoxia | Grade 1-2 laryngeal hemorrhage | Grade 1-2 laryngeal inflammation | Grade 1-2 nasal congestion | Grade 1-2 pleural effusion | Grade 3-5 pleural effusion | Grade 3-5 pneumonitis | Grade 1-2 pneumothorax | Grade 3-5 pneumothorax | Grade 1-2 postnasal drip | Grade 1-2 productive cough | Grade 3-5 pulmonary edema | Grade 3-5 respiratory failure | Grade 1-2 chest pressure with exertion | Grade 1-2 rhinorrhea | Grade 1-2 sore throat | Grade 1-2 wheezing | Grade 1-2 alopecia | Grade 1-2 bullous dermatitis | Grade 1-2 dry skin | Grade 1-2 hyperhidrosis | Grade 1-2 nail changes | Grade 1-2 nail discoloration | Grade 1-2 nail loss | Grade 1-2 palmar-plantar erythrodysesthesia syndrome | Grade 1-2 pruritus | Grade 3-5 pruritus | Grade 1-2 rash acneiform | Grade 1-2 rash maculo-papular | Grade 3-5 rash maculo-papular | Grade 1-2 skin atrophy | Grade 1-2 rash NOS | Grade 3-5 petechial rash | Grade 1-2 skin ulceration | Grade 1-2 urticaria | Grade 1-2 minor gum transplant | Grade 1-2 hot flashes | Grade 1-2 hypertension | Grade 3-5 hypertension | Grade 1-2 hypotension | Grade 3-5 hypotension | Grade 1-2 lymphedema | Grade 1-2 thromboembolic event | Grade 3-5 thromboembolic event | Grade 1-2 peripheral edema | "Grade 1-2 muscle tightness" | Grade 1-2 left hand pain | Grade 1-2 right axillary pain | Grade 1-2 right neck stiffness | "Grade 1-2 frozen thumb" | Grade 1-2 hip pain | Grade 1-2 ankle sprain | Grade 1-2 port site bleed | Grade 1-2 vaginal cyst | Grade 1-2 rash NOS on neck | Grade 1-2 rash NOS on bilateral UE | Grade 1-2 nail bed pain | Grade 1-2 feet peeling | Grade 3-5 leukemia secondary to oncology chemotherapy |
|---|
| Cohort 1, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 11 | 19 | 2 | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 | 3 | 1 | 10 | 0 | 1 | 4 | 1 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 | 1 | 6 | 13 | 0 | 0 | 2 | 0 | 0 | 6 | 1 | 0 | 0 | 0 | 9 | 1 | 0 | 0 | 1 | 16 | 7 | 5 | 1 | 5 | 1 | 3 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 3 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 0 | 0 | 1 | 3 | 0 | 1 | 3 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | 2 | 0 | 2 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 12 | 2 | 12 | 1 | 1 | 0 | 2 | 0 | 2 | 1 | 0 | 0 | 6 | 1 | 1 | 0 | 4 | 0 | 0 | 0 | 0 | 0 | 6 | 18 | 6 | 19 | 6 | 23 | 0 | 6 | 19 | 0 | 5 | 0 | 1 | 0 | 1 | 6 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 6 | 2 | 14 | 1 | 12 | 3 | 1 | 0 | 5 | 2 | 14 | 0 | 6 | 0 | 3 | 4 | 0 | 3 | 1 | 4 | 0 | 6 | 0 | 5 | 0 | 3 | 1 | 1 | 2 | 9 | 0 | 1 | 1 | 8 | 1 | 5 | 0 | 0 | 1 | 2 | 0 | 9 | 0 | 2 | 0 | 2 | 0 | 1 | 3 | 2 | 1 | 4 | 1 | 2 | 0 | 0 | 2 | 1 | 9 | 7 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 5 | 12 | 3 | 6 | 1 | 1 | 0 | 1 | 1 | 1 | 3 | 2 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 2 | 1 | 1 | 2 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 1 | 2 | 0 | 1 | 1 | 0 | 1 | 1 | 2 | 1 | 3 | 1 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
,| Cohort 1, 750 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 9 | 11 | 3 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 2 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 2 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 5 | 0 | 0 | 7 | 1 | 1 | 2 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 5 | 8 | 1 | 1 | 2 | 0 | 1 | 4 | 0 | 1 | 0 | 1 | 5 | 1 | 1 | 0 | 0 | 15 | 7 | 9 | 1 | 0 | 0 | 3 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 3 | 2 | 1 | 0 | 1 | 0 | 5 | 0 | 0 | 3 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 13 | 1 | 11 | 1 | 7 | 1 | 6 | 0 | 0 | 1 | 1 | 0 | 5 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 0 | 7 | 11 | 1 | 18 | 5 | 18 | 3 | 5 | 17 | 0 | 5 | 1 | 4 | 1 | 2 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 5 | 0 | 6 | 2 | 6 | 1 | 1 | 0 | 6 | 1 | 7 | 0 | 1 | 3 | 3 | 3 | 1 | 2 | 1 | 3 | 0 | 2 | 1 | 7 | 1 | 2 | 0 | 0 | 0 | 3 | 0 | 1 | 5 | 5 | 0 | 5 | 1 | 1 | 1 | 2 | 0 | 5 | 0 | 0 | 1 | 1 | 0 | 0 | 2 | 2 | 0 | 1 | 0 | 3 | 0 | 1 | 0 | 2 | 3 | 7 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 6 | 4 | 1 | 6 | 1 | 0 | 1 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 1 | 0 | 2 | 3 | 1 | 2 | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 3 | 1 | 0 | 2 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 1 |
,| Cohort 1, 900 mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 12 | 12 | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 2 | 1 | 1 | 1 | 1 | 1 | 0 | 1 | 1 | 1 | 8 | 0 | 0 | 7 | 2 | 0 | 3 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 3 | 14 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 0 | 0 | 10 | 1 | 0 | 1 | 0 | 10 | 8 | 5 | 1 | 0 | 0 | 1 | 1 | 1 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 4 | 0 | 1 | 2 | 1 | 0 | 4 | 0 | 4 | 1 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 3 | 2 | 8 | 3 | 13 | 0 | 8 | 2 | 6 | 1 | 1 | 0 | 1 | 1 | 9 | 0 | 0 | 0 | 9 | 0 | 3 | 0 | 1 | 1 | 4 | 20 | 6 | 11 | 9 | 12 | 0 | 5 | 15 | 1 | 5 | 1 | 1 | 1 | 1 | 5 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 6 | 4 | 13 | 2 | 11 | 1 | 2 | 2 | 7 | 3 | 11 | 1 | 4 | 2 | 2 | 4 | 1 | 3 | 0 | 4 | 1 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 2 | 8 | 0 | 3 | 0 | 0 | 2 | 0 | 0 | 10 | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 8 | 7 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 5 | 6 | 1 | 3 | 1 | 0 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 2 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 1 | 0 | 1 | 4 | 0 | 1 | 1 | 1 | 0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Cohort 2, 600mg/m2 Gemcitabine Dose Level: ADI-PEG 20 + Gemcitabine + Docetaxel | 9 | 4 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 1 | 0 | 2 | 1 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 5 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 5 | 1 | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 8 | 3 | 7 | 4 | 7 | 2 | 2 | 9 | 0 | 2 | 0 | 0 | 0 | 1 | 2 | 0 | 2 | 0 | 0 | 0 | 1 | 1 | 2 | 0 | 1 | 2 | 2 | 2 | 0 | 0 | 2 | 1 | 5 | 1 | 3 | 0 | 0 | 0 | 0 | 2 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 3 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 4 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Clinical Benefit Rate (CBR) (Cohort 1 Only)
"CBR = proportion of patients who have experienced complete response (CR)+ partial response (PR) + stable disease (SD) lasting 24 weeks or longer~CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).~PR: At least a 30% decrease in the sum of the 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." (NCT03449901)
Timeframe: Through completion of treatment (median treatment of 9 months)
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel | 27 |
Overall Survival (OS) (Cohort 1 Only)
-OS: defined as time on study to time of death due to any reasons or latest follow-up (whichever is earlier) (NCT03449901)
Timeframe: Through completion of follow-up (median follow-up 494 days, full range of 5-1500 days).
| Intervention | months (Median) |
|---|
| Cohort 1: ADI-PEG 20 + Gemcitabine + Docetaxel | 18.1359 |
Duration of Response (DOR) as Per RECIST V1.1
DOR: time from the date of the first CR/PR (whichever is first recorded) that was subsequently confirmed as assessed by investigator to the date of documented PD or death due to any cause whichever occurred first. If a participant has neither progressed nor died, the participant was censored at the date of last RA or at the date of first CR/PR if no subsequent post-baseline RA was available. Participants who received any further ACT for the disease before radiological progression were censored at the date of the last RA before the ACT started. In addition, participants who had PD/death after >= 2 missed RAs were censored at the last RA prior to the 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow up for DOR was based on data cut-off and is same as median follow-up time for OS. CR/PR and PD were defined in ORR and PFS1 endpoints, respectively. (NCT03474107)
Timeframe: From date of first objective response until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
| Intervention | months (Median) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | 7.39 |
| Chemotherapy | 8.11 |
Change From Baseline to Week 12 in European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire Global Health Status (QL2 Score)
"EORTC QLQ-C30 is a generic questionnaire consisting of 30 items. The instrument yields functional scales (physical, role, emotional, cognitive, social), symptom scales/items (fatigue, Nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea), global health status, and financial impact score. Most items are scored 1 (not at all) to 4 (very much) except for the items contributing to the global health status/QoL, which are scored 1 (very poor) to 7 (excellent). The recall period for each question is during the past week. All raw domain scores are linearly transformed to a 0-100 scale with higher scores on symptoms indicate a worse health state. Higher scores on the global health status and functioning scales indicate better health status/function." (NCT03474107)
Timeframe: Baseline and week 12
| Intervention | score on a scale (Mean) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | -2.30 |
| Chemotherapy | -5.72 |
Change From Baseline to Week 12 in EuroQOL 5-dimension 5-level Questionnaire [EQ-5D-5L] Visual Analog Scale (VAS)
EQ-5D-5L is a health status instrument for self-reported assessment of 5 domains of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each domain is rated by selecting 1 of 5 standardized categorizations ranging from no problem to extreme problem. The final question is a visual analogue scale (VAS) to rank health status from 0 (best health imaginable) to 100 (worst health imaginable). (NCT03474107)
Timeframe: Baseline and week 12
| Intervention | score on a scale (Mean) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | -1.8 |
| Chemotherapy | -5.3 |
Overall Survival (OS)
OS was defined as the time from the date of randomization until the documented date of death from any cause. OS was analyzed using Kaplan-Meier estimates. Participants who were still alive at the time of data cutoff date were to be censored at the last known alive date or at the data cutoff date, whichever was earlier. (NCT03474107)
Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
| Intervention | months (Median) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | 12.88 |
| Chemotherapy | 8.97 |
Number of Participants With Treatment Emergent Adverse Events
An AE is any untoward medical occurrence in a participant 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. A TEAE is defined as an AE observed or worsened after starting administration of the study drug. (NCT03474107)
Timeframe: From first dose up to 30 days after last dose (Median (range) time on study drug was 4.99 (0.5, 19.4) months in enfortumab vedotin and 3.45 (0.2, 15.0) months in chemotherapy group)
| Intervention | participants (Number) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | 290 |
| Chemotherapy | 288 |
Disease Control Rate (DCR) as Per RECIST V1.1
DCR was defined as the percentage of participants with a CR, PR or a stable disease (SD) based on RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD was defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters while on study drug. Progressive disease is defined in PFS1 endpoint. DCR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for DCR was based on data cut-off and is same as median follow-up time for OS. (NCT03474107)
Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
| Intervention | percentage of participants (Number) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | 71.9 |
| Chemotherapy | 53.4 |
Progression Free Survival on Study Therapy (PFS1) as Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
PFS: time from date of randomization until date of documented radiological disease progression (PD) per investigator based on RECIST V1.1, or until death due to any cause, whichever occurred first. PD: >= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of >= 5 mm. Appearance of 1 or more new lesions is also considered progression. A participant who neither progressed nor died was censored at date of last radiological assessment (RA)/ date of randomization if no post-baseline RA was available. Participants who received any further anticancer therapy (ACT) for disease before radiological progression was censored at date of last RA before ACT started and participants who had PD/death after >=2 missed RAs were censored at last RA prior to 2 or more missed RAs. Kaplan-Meier estimates was used. Median time of follow-up for PFS was based on data cut-off & is same as median follow-up time for OS. (NCT03474107)
Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
| Intervention | months (Median) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | 5.55 |
| Chemotherapy | 3.71 |
Overall Response Rate (ORR) as Per RECIST V1.1
ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) based on the RECIST v1.1. CR was defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to < 10 mm from baseline measurement. PR was defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. ORR was analysed using exact method based on binomial distribution (Clopper-Pearson). Median time of follow up for ORR was based on data cut-off and is same as median follow-up time for OS. (NCT03474107)
Timeframe: From randomization until the analysis cut-off date of 15-Jul-2020 (median OS follow-up was 11.10 months)
| Intervention | percentage of participants (Number) |
|---|
| Enfortumab Vedotin 1.25 mg/kg | 40.6 |
| Chemotherapy | 17.9 |
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
| Intervention | ratio (Least Squares Mean) |
|---|
| Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg | 0.962 |
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
| Intervention | hour (Mean) |
|---|
| Pevonedistat without rifampin (Day 1) | Pevonedistat with rifampin (Day 10) |
|---|
| Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg | 7.442 | 5.708 |
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
| Intervention | liter per hour (L/h) (Mean) |
|---|
| Pevonedistat without rifampin (Day 1) | Pevonedistat with rifampin (Day 10) |
|---|
| Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg | 35.22 | 43.77 |
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
| Intervention | liter (Mean) |
|---|
| Pevonedistat without rifampin (Day 1) | Pevonedistat with rifampin (Day 10) |
|---|
| Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg | 312.82 | 296.10 |
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)
| Intervention | Participants (Count of Participants) |
|---|
| CR | PR | SD | PD |
|---|
| Part B: Pevonedistat 20 mg/m^2 + Carboplatin AUC5 + Paclitaxel 175 mg/m^2 | 0 | 1 | 3 | 3 |
,| Part B: Pevonedistat 25 mg/m^2 + Docetaxel 75 mg/m^2 | 0 | 2 | 2 | 2 |
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
| Intervention | ratio (Least Squares Mean) |
|---|
| Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg | 0.790 |
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
| Intervention | ratio (Least Squares Mean) |
|---|
| Part A: Pevonedistat 50 mg/m^2 + Rifampin 600 mg | 0.785 |
Number of Participants With a Secondary Cardiac Event
A secondary cardiac event is defined as asymptomatic or mildly symptomatic Left Ventricular Systolic Dysfunction (LVSD) of NYHA Class II, defined as a left ventricular ejection fraction (LVEF) decrease of at least 10-percentage points below the baseline measurement to an absolute LVEF value of <50% confirmed by a second assessment within approximately 3 weeks (NCT03493854)
Timeframe: From Baseline until the primary completion date (up to 1 year, 1 month)
| Intervention | Participants (Count of Participants) |
|---|
| Any Secondary Cardiac Event | Identified by Initial LVEF Assessment | Confirmed by Second LVEF Assessment |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 9 | 9 | 2 |
,| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 4 | 4 | 1 |
Trough Serum Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)
The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement. (NCT03493854)
Timeframe: Pre-dose on Cycle 8, Day 1 (up to 21 weeks)
| Intervention | micrograms per millilitre (μg/mL) (Geometric Mean) |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 72.4 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 88.7 |
Summary of the Number of Participants With at Least One Adverse Event, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4 (NCI CTCAE v4)
"The adverse event (AE) severity grading scale for the NCI CTCAE v4.0 was used for assessing AE severity. Any AEs that were not specifically listed in the NCI CTCAE, v4.0 were graded per the following 5 grades: Grade 1 = mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; or intervention not indicated. Grade 2 = moderate; minimal, local, or non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living. Grade 3 = severe or medically significant, but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living. Grade 4 = life-threatening consequences or urgent intervention indicated. Grade 5 = death related to AE. The terms severe and serious are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade." (NCT03493854)
Timeframe: From Baseline until the primary completion date (up to 1 year, 1 month)
| Intervention | Participants (Count of Participants) |
|---|
| Any Adverse Event (AE): Any Grade | Any AE: Grade 1 | Any AE: Grade 2 | Any AE: Grade 3 | Any AE: Grade 4 | Any AE: Grade 5 | Any AE: Grades 3 to 5 | Any Serious AE | Anaphylaxis and Hypersensitivity AEs | Infusion/Admin.-Related Reactions Within 24 hrs | Serious Rash/Skin Reactions | Diarrhoea | Cardiac Dysfunction | Interstitial Lung Disease | Neutropenia/Febrile Neutropenia | Serious Mucositis | Pregnancy- and Neonatal-Related AEs |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 251 | 11 | 107 | 87 | 45 | 1 | 133 | 45 | 5 | 34 | 0 | 139 | 41 | 2 | 133 | 4 | 1 |
,| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 248 | 9 | 118 | 79 | 41 | 1 | 121 | 40 | 4 | 43 | 1 | 145 | 41 | 3 | 119 | 3 | 1 |
Number of Participants With Laboratory Test Abnormalities at the Highest NCI CTCAE v4 Grade Post-Baseline
Clinical laboratory tests were performed at local laboratories; any abnormal values (High or Low) were based on local laboratory normal ranges. Laboratory abnormalities are presented by the highest (worst) severity grade (according to NCI-CTCAE v4.0) post-baseline. Not every abnormal laboratory value qualified as an adverse event, only if it met any of the following criteria: clinically significant (per investigator); accompanied by clinical symptoms; resulted in a change in study treatment; or required a medical intervention or a change in concomitant therapy. For a participant with multiple post-baseline abnormalities, only the highest (worst) grade for a given laboratory test is reported. 'Any Grade' indicates the total number of participants with a post-baseline abnormality of any grade for the specified test. Abs. = absolute count; SGOT/AST = serum glutamic-oxaloacetic transaminase/aspartate transaminase; SGPT/ALT = serum glutamic-pyruvic transaminase/alanine transaminase (NCT03493854)
Timeframe: Day 1 of Cycles 1 to 8 (up to 21 weeks)
| Intervention | Participants (Count of Participants) |
|---|
| Albumin, Low - Any Grade | Albumin, Low - Grade 1 | Albumin, Low - Grade 2 | Albumin, Low - Grade 3 | Alkaline Phosphatase, High - Any Grade | Alkaline Phosphatase, High - Grade 1 | Alkaline Phosphatase, High - Grade 2 | SGPT/ALT, High - Any Grade | SGPT/ALT, High - Grade 1 | SGPT/ALT, High - Grade 2 | SGPT/ALT, High - Grade 3 | SGOT/AST, High - Any Grade | SGOT/AST, High - Grade 1 | SGOT/AST, High - Grade 2 | SGOT/AST, High - Grade 3 | Creatinine, High - Any Grade | Creatinine, High - Grade 1 | Creatinine, High - Grade 2 | Creatinine, High - Grade 3 | Glucose, Low - Any Grade | Glucose, Low - Grade 1 | Glucose, Low - Grade 2 | Glucose, Low - Grade 3 | Glucose, High - Any Grade | Glucose, High - Grade 3 | Hemoglobin, Low - Any Grade | Hemoglobin, Low - Grade 1 | Hemoglobin, Low - Grade 2 | Hemoglobin, Low - Grade 3 | Hemoglobin, High - Any Grade | Hemoglobin, High - Grade 1 | Lymphocytes, Abs., Low - Any Grade | Lymphocytes, Abs., Low - Grade 1 | Lymphocytes, Abs., Low - Grade 2 | Lymphocytes, Abs., Low - Grade 3 | Lymphocytes, Abs., Low - Grade 4 | Lymphocytes, Abs., High - Any Grade | Lymphocytes, Abs., High - Grade 1 | Neutrophils, Total, Abs., Low - Any Grade | Neutrophils, Total, Abs., Low - Grade 1 | Neutrophils, Total, Abs., Low - Grade 2 | Neutrophils, Total, Abs., Low - Grade 3 | Neutrophils, Total, Abs., Low - Grade 4 |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 49 | 40 | 8 | 1 | 34 | 32 | 2 | 166 | 146 | 14 | 6 | 137 | 129 | 6 | 2 | 193 | 187 | 5 | 1 | 22 | 18 | 3 | 1 | 3 | 3 | 231 | 131 | 90 | 10 | 10 | 10 | 140 | 29 | 59 | 45 | 7 | 3 | 3 | 108 | 27 | 29 | 16 | 36 |
,| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 39 | 34 | 5 | 0 | 41 | 40 | 1 | 138 | 123 | 12 | 3 | 113 | 110 | 1 | 2 | 194 | 186 | 8 | 0 | 21 | 21 | 0 | 0 | 4 | 4 | 220 | 138 | 76 | 6 | 4 | 4 | 138 | 19 | 67 | 48 | 4 | 3 | 3 | 106 | 35 | 22 | 24 | 25 |
Number of Participants With a Primary Cardiac Event
A primary cardiac event is defined as the occurrence of either of the following events: - Incidence of a symptomatic ejection fraction decrease (heart failure) of New York Heart Association (NYHA) Class III or IV and a drop in left ventricular ejection fraction (LVEF) of at least 10-percentage points from baseline and to below 50%; or - Cardiac death, defined as: 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). (NCT03493854)
Timeframe: From Baseline until the primary completion date (up to 1 year, 1 month)
| Intervention | Participants (Count of Participants) |
|---|
| Any Primary Cardiac Event | Heart Failure and Significant LVEF Decline | Cardiac Death (Definite or Probable) |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 0 | 0 | 0 |
,| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 2 | 1 | 1 |
Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment
Total pCR (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated. The lower bound of the CI will reliably reflect the largest tpCR difference that can be considered unlikely. (NCT03493854)
Timeframe: Following completion of surgery (up to 33 weeks)
| Intervention | Percentage of participants (Number) |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 59.5 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 59.7 |
Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)
The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a subcutaneous injection site other than thigh was used, if the Cycle 8 pre-dose and post-dose samples were switched, and an assay error impacting Ctrough measurement. (NCT03493854)
Timeframe: Pre-dose on Cycle 8, Day 1 (up to 21 weeks)
| Intervention | micrograms per milllilitre (μg/mL) (Geometric Mean) |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 43.2 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 57.5 |
Randomized Part: Time to Definitive 10-point Deterioration in Global Health Status (GHS)/Quality of Life (QoL), Shortness of Breath and Pain Per EORTC QLQ-C30 Questionnaire
The EORTC QLQ-C30 includes 5 functional scales (physical,role,cognitive,emotional and social), 3 symptom scales (fatigue,pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation,diarrhea,insomnia,shortness of breath,appetite loss and financial difficulties). For each scale and single-item, scores range between 0 and 100. A high score for functional scales/ GHS/QoL represents better functioning or QoL, a high score for symptom scales/single items represents significant symptomatology. TTD in GHS/QoL, shortness of breath and pain is defined as the time from randomization to the date of event, defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold i.e.<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment. (NCT03626545)
Timeframe: From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
| Intervention | Months (Median) |
|---|
| GHS/QOL | Shortness of breath | Pain |
|---|
| Randomized Part: Canakinumab + Docetaxel | 4.83 | 6.57 | 6.05 |
,| Randomized Part: Placebo + Docetaxel | 7.16 | 5.78 | 8.54 |
Randomized Part: Time to Definitive 10-point Deterioration (TTD) Symptom Scores of Chest Pain, Cough and Dyspnea Per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Lung Cancer (LC13) Questionnaire
The EORTC QLQ-LC13 comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie. hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher level of symptoms. TTD for chest pain, cough and dyspnea is defined as the time from randomization to the date of event, which is defined as at least 10 points absolute worsening from baseline of the corresponding scale score, with no later change below this threshold ie.<10 points was observed or if this worsening was observed at the last assessment for the subject, or death due to any cause (whichever occurs earlier). If a subject did not have an event, TTD was censored at the last adequate assessment. (NCT03626545)
Timeframe: From baseline through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 18 months)
| Intervention | Months (Median) |
|---|
| Chest Pain | Cough | Dyspnea |
|---|
| Randomized Part: Canakinumab + Docetaxel | 7.23 | 7.23 | 3.45 |
,| Randomized Part: Placebo + Docetaxel | 13.14 | 13.14 | 4.27 |
Randomized Part: Pre-dose Plasma Trough Concentration (CTrough) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. CTrough of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT03626545)
Timeframe: Pre-dose on Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 and Cycle 18 Day 1. Each cycle is 21 days.
| Intervention | microgram/miliLiter (ug/mL) (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 4 Day 1 | Cycle 6 Day 1 | Cycle 12 Day 1 | Cycle 18 Day 1 |
|---|
| Randomized Part: Canakinumab + Docetaxel | 0 | 20.5 | 23.7 | 25.6 | 28.3 |
Randomized Part: Cmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT03626545)
Timeframe: Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
| Intervention | nanogram/miliLiter (ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 4 Day 1 |
|---|
| Randomized Part: Canakinumab + Docetaxel | 1570 | 1530 |
,| Randomized Part: Placebo + Docetaxel | 1190 | 940 |
Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire
The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation, diarrhea, insomnia, dyspnoea, appetite loss and financial difficulties). For each scale and item, scores range 0-100. A high score for functional scales/QoL represents better functioning/QoL; a high score for symptom scales and items represents significant symptomatology. Changes from baseline in QoL, shortness of breath and pain scores are presented. For QoL, a negative change from baseline indicates improvement; for shortness of breath and pain a positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression (NCT03626545)
Timeframe: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
| Intervention | Score on a scale (Mean) |
|---|
| GHS/QoL: Week 3 | GHS/QoL: Week 6 | GHS/QoL: Week 9 | GHS/QoL: Week 12 | GHS/QoL: Week 15 | GHS/QoL: Week 18 | GHS/QoL: Week 21 | GHS/QoL: Week 24 | GHS/QoL: Week 27 | GHS/QoL: Week 30 | GHS/QoL: Week 33 | GHS/QoL: Week 36 | GHS/QoL: Week 39 | GHS/QoL: Week 42 | GHS/QoL: Week 45 | GHS/QoL: Week 48 | GHS/QoL: Week 51 | GHS/QoL: Week 54 | GHS/QoL: Week 57 | GHS/QoL: Week 60 | GHS/QoL: Week 63 | GHS/QoL: Week 66 | GHS/QoL: Week 69 | GHS/QoL: Week 72 | GHS/QoL: Week 75 | GHS/QoL: Week 78 | GHS/QoL: post treatment efficacy visit 1 | GHS/QoL: post treatment efficacy visit 2 | GHS/QoL: post treatment efficacy visit 3 | GHS/QoL: post treatment efficacy visit 5 | GHS/QoL: 7 days post disease progression | GHS/QoL: 28 days post disease progression | Shortness of breath: Week 3 | Shortness of breath: Week 6 | Shortness of breath: Week 9 | Shortness of breath: Week 12 | Shortness of breath: Week 15 | Shortness of breath: Week 18 | Shortness of breath: Week 21 | Shortness of breath: Week 24 | Shortness of breath: Week 27 | Shortness of breath: Week 30 | Shortness of breath: Week 33 | Shortness of breath: Week 36 | Shortness of breath: Week 39 | Shortness of breath: Week 42 | Shortness of breath: Week 45 | Shortness of breath: Week 48 | Shortness of breath: Week 51 | Shortness of breath: Week 54 | Shortness of breath: Week 57 | Shortness of breath: Week 60 | Shortness of breath: Week 63 | Shortness of breath: Week 66 | Shortness of breath: Week 69 | Shortness of breath: Week 72 | Shortness of breath: Week 75 | Shortness of breath: Week 78 | Shortness of breath: post treatment efficacy visit 1 | Shortness of breath: post treatment efficacy visit 2 | Shortness of breath: post treatment efficacy visit 3 | Shortness of breath: post treatment efficacy visit 5 | Shortness of breath: 7 days post disease progression | Shortness of breath: 28 days post disease progression | Pain: Week 3 | Pain: Week 6 | Pain: Week 9 | Pain: Week 12 | Pain: Week 15 | Pain: Week 18 | Pain: Week 21 | Pain: Week 24 | Pain: Week 27 | Pain: Week 30 | Pain: Week 33 | Pain: Week 36 | Pain: Week 39 | Pain: Week 42 | Pain: Week 45 | Pain: Week 48 | Pain: Week 51 | Pain: Week 54 | Pain: Week 57 | Pain: Week 60 | Pain: Week 63 | Pain: Week 66 | Pain: Week 69 | Pain: Week 72 | Pain: Week 75 | Pain: Week 78 | Pain: post treatment efficacy visit 1 | Pain: post treatment efficacy visit 2 | Pain: post treatment efficacy visit 3 | Pain: post treatment efficacy visit 5 | Pain: 7 days post disease progression | Pain: 28 days post disease progression |
|---|
| Randomized Part: Placebo + Docetaxel | 1.8 | 1.4 | -0.4 | 2.5 | -4.2 | 2.8 | -4.2 | -0.7 | -2.2 | -5.7 | 0.4 | 3.3 | 1.2 | 2.8 | -3.5 | -13.9 | -6.7 | -4.8 | -8.3 | 2.1 | 2.8 | -8.3 | 0.0 | -8.3 | -16.7 | -16.7 | 5.6 | 16.7 | -8.3 | 25.0 | -4.6 | -7.8 | 31.7 | 4.0 | 5.7 | 4.4 | 7.3 | 3.5 | 29.8 | 6.9 | -1.2 | 5.3 | -1.7 | -2.2 | 40.5 | -6.7 | 8.3 | 3.7 | 0.0 | 9.5 | 20.0 | 16.7 | 0.0 | 0.0 | -16.7 | -16.7 | 33.3 | 33.3 | 33.3 | 0.0 | 16.7 | 0.00 | 8.0 | 15.7 | -2.0 | -1.6 | -3.1 | -1.4 | 0.7 | 0.7 | 0.0 | 19.1 | 1.2 | 4.0 | 6.7 | 26.7 | 10.7 | 11.1 | 15.3 | 5.6 | 8.3 | -2.4 | 6.7 | 0.0 | -16.7 | 0.0 | 8.3 | 0.0 | 0.0 | 0.0 | -11.1 | 0.0 | 33.3 | 0.0 | 2.3 | 13.7 |
Randomized Part: Change From Baseline in GHS/QoL, Shortness of Breath and Pain Scores as Per the EORTC QLQ C30 Questionnaire
The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social), 3 symptom scales (fatigue, pain and nausea/vomiting), a GHS/QoL scale, and 6 single items (constipation, diarrhea, insomnia, dyspnoea, appetite loss and financial difficulties). For each scale and item, scores range 0-100. A high score for functional scales/QoL represents better functioning/QoL; a high score for symptom scales and items represents significant symptomatology. Changes from baseline in QoL, shortness of breath and pain scores are presented. For QoL, a negative change from baseline indicates improvement; for shortness of breath and pain a positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression (NCT03626545)
Timeframe: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
| Intervention | Score on a scale (Mean) |
|---|
| GHS/QoL: Week 3 | GHS/QoL: Week 6 | GHS/QoL: Week 9 | GHS/QoL: Week 12 | GHS/QoL: Week 15 | GHS/QoL: Week 18 | GHS/QoL: Week 21 | GHS/QoL: Week 24 | GHS/QoL: Week 27 | GHS/QoL: Week 30 | GHS/QoL: Week 33 | GHS/QoL: Week 36 | GHS/QoL: Week 39 | GHS/QoL: Week 42 | GHS/QoL: Week 45 | GHS/QoL: Week 48 | GHS/QoL: Week 51 | GHS/QoL: Week 54 | GHS/QoL: Week 57 | GHS/QoL: Week 60 | GHS/QoL: Week 63 | GHS/QoL: Week 66 | GHS/QoL: Week 69 | GHS/QoL: post treatment efficacy visit 1 | GHS/QoL: post treatment efficacy visit 2 | GHS/QoL: 7 days post disease progression | GHS/QoL: 28 days post disease progression | Shortness of breath: Week 3 | Shortness of breath: Week 6 | Shortness of breath: Week 9 | Shortness of breath: Week 12 | Shortness of breath: Week 15 | Shortness of breath: Week 18 | Shortness of breath: Week 21 | Shortness of breath: Week 24 | Shortness of breath: Week 27 | Shortness of breath: Week 30 | Shortness of breath: Week 33 | Shortness of breath: Week 36 | Shortness of breath: Week 39 | Shortness of breath: Week 42 | Shortness of breath: Week 45 | Shortness of breath: Week 48 | Shortness of breath: Week 51 | Shortness of breath: Week 54 | Shortness of breath: Week 57 | Shortness of breath: Week 60 | Shortness of breath: Week 63 | Shortness of breath: Week 66 | Shortness of breath: Week 69 | Shortness of breath: post treatment efficacy visit 1 | Shortness of breath: post treatment efficacy visit 2 | Shortness of breath: 7 days post disease progression | Shortness of breath: 28 days post disease progression | Pain: Week 3 | Pain: Week 6 | Pain: Week 9 | Pain: Week 12 | Pain: Week 15 | Pain: Week 18 | Pain: Week 21 | Pain: Week 24 | Pain: Week 27 | Pain: Week 30 | Pain: Week 33 | Pain: Week 36 | Pain: Week 39 | Pain: Week 42 | Pain: Week 45 | Pain: Week 48 | Pain: Week 51 | Pain: Week 54 | Pain: Week 57 | Pain: Week 60 | Pain: Week 63 | Pain: Week 66 | Pain: Week 69 | Pain: post treatment efficacy visit 1 | Pain: post treatment efficacy visit 2 | Pain: 7 days post disease progression | Pain: 28 days post disease progression |
|---|
| Randomized Part: Canakinumab + Docetaxel | -0.5 | -3.3 | -2.7 | -7.4 | -2.9 | -3.9 | -3.5 | -3.6 | -4.7 | -3.7 | -3.2 | -4.5 | -5.8 | -9.2 | -3.6 | -8.3 | -8.3 | -6.9 | -12.5 | -8.3 | -5.6 | 8.3 | 16.7 | -16.7 | -16.7 | -7.5 | -3.7 | 31.2 | 7.3 | 6.7 | 12.2 | 7.8 | 8.5 | 34.2 | 4.8 | 13.0 | 16.7 | 17.9 | 9.1 | 33.3 | 23.3 | 9.5 | 22.2 | 16.7 | 11.1 | 8.3 | 0.0 | 0.0 | -16.7 | 0.0 | 33.3 | 0.0 | 8.6 | 3.7 | -5.1 | -5.1 | -4.1 | 2.2 | -0.7 | 2.3 | 3.3 | 25.2 | 1.4 | 2.8 | -8.3 | 22.7 | -10.0 | -3.3 | -11.9 | -5.6 | 2.8 | 8.3 | 0.0 | 16.7 | 5.6 | 0.0 | 33.3 | -33.3 | 0.0 | 1.6 | 9.3 |
Randomized Part: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores
The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The 5 digit health states obtained for each dimension was converted into a single mean index value based on the EQ-5D crosswalk value set for the UK using the time trade-off method. This index ranges from -0.594 (worst health) to 1.0 (best health). A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression (NCT03626545)
Timeframe: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
| Intervention | Score on a scale (Mean) |
|---|
| Week 3 | Week 6 | Week 9 | Week 12 | Week 15 | Week 18 | Week 21 | Week 24 | Week 27 | Week 30 | Week 33 | Week 36 | Week 39 | Week 42 | Week 45 | Week 48 | Week 51 | Week 54 | Week 57 | Week 60 | Week 63 | Week 66 | Week 69 | Week 72 | Week 75 | Week 78 | Post treatment efficacy visit 1 | Post treatment efficacy visit 2 | Post treatment efficacy visit 3 | Post treatment efficacy visit 5 | 7 days post disease progression | 28 days post disease progression |
|---|
| Randomized Part: Placebo + Docetaxel | -0.007 | 0.001 | 0.011 | 0.014 | -0.042 | 0.009 | 0.005 | 0.027 | 0.008 | -0.014 | 0.029 | 0.050 | -0.012 | 0.116 | -0.036 | 0.003 | 0.071 | 0.056 | 0.652 | 0.149 | 0.165 | 0.124 | 0.340 | 0.168 | 0.130 | 0.130 | -0.026 | 0.704 | 0.601 | 1.000 | 0.657 | 0.692 |
Randomized Part: Change From Baseline in European Quality of Life-5 Dimensions-5 Level (EQ-5D-5L) Health State Scores
The EQ-5D-5L descriptive system provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each of these dimensions, the participant self-assigned a score: from 1 (no problems) to 5 (extreme problems). The 5 digit health states obtained for each dimension was converted into a single mean index value based on the EQ-5D crosswalk value set for the UK using the time trade-off method. This index ranges from -0.594 (worst health) to 1.0 (best health). A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression (NCT03626545)
Timeframe: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
| Intervention | Score on a scale (Mean) |
|---|
| Week 3 | Week 6 | Week 9 | Week 12 | Week 15 | Week 18 | Week 21 | Week 24 | Week 27 | Week 30 | Week 33 | Week 36 | Week 39 | Week 42 | Week 45 | Week 48 | Week 51 | Week 54 | Week 57 | Week 60 | Week 63 | Week 66 | Week 69 | Post treatment efficacy visit 1 | Post treatment efficacy visit 2 | 7 days post disease progression | 28 days post disease progression |
|---|
| Randomized Part: Canakinumab + Docetaxel | -0.017 | -0.016 | -0.006 | -0.028 | -0.057 | -0.062 | -0.097 | -0.070 | -0.043 | -0.023 | -0.031 | 0.017 | -0.007 | -0.010 | 0.017 | -0.087 | -0.151 | -0.102 | 0.476 | -0.193 | -0.140 | 0.034 | 0.000 | 0.100 | 0.644 | 0.639 | 0.692 |
Randomized Part: Change From Baseline in Chest Pain, Cough and Dyspnea Scores as Per the EORTC-QLQ LC13 Questionnaire
"The EORTC QLQ-LC13 is a 13-item questionnaire. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher (worse) level of symptoms. Changes from baseline in chest pain, cough and dyspnea scores are presented. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression" (NCT03626545)
Timeframe: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
| Intervention | Score on a scale (Mean) |
|---|
| Chest pain: Week 3 | Chest pain: Week 6 | Chest pain: Week 9 | Chest pain: Week 12 | Chest pain: Week 15 | Chest pain: Week 18 | Chest pain: Week 21 | Chest pain: Week 24 | Chest pain: Week 27 | Chest pain: Week 30 | Chest pain: Week 33 | Chest pain: Week 36 | Chest pain: Week 39 | Chest pain: Week 42 | Chest pain: Week 45 | Chest pain: Week 48 | Chest pain: Week 51 | Chest pain: Week 54 | Chest pain: Week 57 | Chest pain: Week 60 | Chest pain: Week 63 | Chest pain: Week 66 | Chest pain: Week 69 | Chest pain: Week 72 | Chest pain: Week 75 | Chest pain: Week 78 | Chest pain:Post treatment efficacy visit 1 | Chest pain: Post treatment efficacy visit 2 | Chest pain: Post treatment efficacy visit 3 | Chest pain: Post treatment efficacy visit 5 | Chest pain: 7 days post disease progression | Chest pain: 28 days post disease progression | Coughing: Week 3 | Coughing: Week 6 | Coughing: Week 9 | Coughing: Week 12 | Coughing: Week 15 | Coughing: Week 18 | Coughing: Week 21 | Coughing: Week 24 | Coughing: Week 27 | Coughing: Week 30 | Coughing: Week 33 | Coughing: Week 36 | Coughing: Week 39 | Coughing: Week 42 | Coughing: Week 45 | Coughing: Week 48 | Coughing: Week 51 | Coughing: Week 54 | Coughing: Week 57 | Coughing: Week 60 | Coughing: Week 63 | Coughing: Week 66 | Coughing: Week 69 | Coughing: Week 72 | Coughing: Week 75 | Coughing: Week 78 | Coughing: Post treatment efficacy visit 1 | Coughing: Post treatment efficacy visit 2 | Coughing: Post treatment efficacy visit 3 | Coughing: Post treatment efficacy visit 5 | Coughing: 7 days post disease progression | Coughing: 28 days post disease progression | Dyspnea: Week 3 | Dyspnea: Week 6 | Dyspnea: Week 9 | Dyspnea: Week 12 | Dyspnea: Week 15 | Dyspnea: Week 18 | Dyspnea: Week 21 | Dyspnea: Week 24 | Dyspnea: Week 27 | Dyspnea: Week 30 | Dyspnea: Week 33 | Dyspnea: Week 36 | Dyspnea: Week 39 | Dyspnea: Week 42 | Dyspnea: Week 45 | Dyspnea: Week 48 | Dyspnea: Week 51 | Dyspnea: Week 54 | Dyspnea: Week 57 | Dyspnea: Week 60 | Dyspnea: Week 63 | Dyspnea: Week 66 | Dyspnea: Week 69 | Dyspnea: Week 72 | Dyspnea: Week 75 | Dyspnea: Week 78 | Dyspnea: Post treatment efficacy visit 1 | Dyspnea: Post treatment efficacy visit 2 | Dyspnea: Post treatment efficacy visit 3 | Dyspnea: Post treatment efficacy visit 5 | Dyspnea: 7 days post disease progression | Dyspnea: 28 days post disease progression |
|---|
| Randomized Part: Placebo + Docetaxel | -3.2 | -3.9 | -3.8 | -3.3 | -0.7 | -4.1 | 0.9 | -1.0 | 6.2 | 6.7 | 0.0 | 0.0 | 9.5 | 0.0 | 8.3 | 11.1 | 10.0 | 9.5 | 20.0 | 25.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 33.3 | -22.2 | 0.0 | 16.7 | 0.0 | -5.7 | -2.1 | -3.2 | -4.7 | 0.5 | 0.0 | -0.7 | 0.0 | -4.4 | -3.9 | -1.2 | -4.0 | -3.5 | -6.7 | -4.8 | -8.9 | 2.8 | 3.7 | -3.3 | -4.8 | 6.7 | -8.3 | -11.1 | -16.7 | -33.3 | -33.3 | 0.0 | 0.0 | 0.0 | 33.3 | -16.7 | 0.0 | 3.4 | -4.2 | 2.9 | 5.0 | 5.2 | 6.9 | 10.9 | 4.3 | 6.7 | 9.2 | 8.6 | 8.0 | 7.0 | 7.4 | 10.3 | 3.0 | 13.0 | 14.8 | 7.8 | 12.7 | 11.1 | -2.8 | -3.7 | 0.0 | -11.1 | -11.1 | 22.2 | 22.2 | 3.7 | 22.2 | 16.7 | -11.1 | 2.3 | 10.4 |
Randomized Part: Change From Baseline in Chest Pain, Cough and Dyspnea Scores as Per the EORTC-QLQ LC13 Questionnaire
"The EORTC QLQ-LC13 is a 13-item questionnaire. It comprises both multi-item and single-item measures of lung cancer-associated symptoms (ie, coughing, dyspnea, and chest pain) and treatment-related symptoms from conventional chemotherapy and radiotherapy (ie, hair loss, neuropathy, sore mouth, and dysphagia). Scores for each scale and single-item range from 0 to 100, with higher scores indicating higher (worse) level of symptoms. Changes from baseline in chest pain, cough and dyspnea scores are presented. A positive change from baseline indicates improvement. For subjects who discontinued treatment without disease progression, post-treatment efficacy visits 1, 2, 3 and 5 were conducted every 6 weeks (for the first 12 months since start of treatment) and every 12 weeks (after 12 months since start of treatment) until disease progression" (NCT03626545)
Timeframe: Baseline, every 3 weeks from Week 3 until end of treatment, every 6 or 12 weeks post-treatment until progression (post-treatment efficacy visits), 7 and 28 days post progression through final analysis cutoff date of 08Jan2021 (up to approx. 18 months)
| Intervention | Score on a scale (Mean) |
|---|
| Chest pain: Week 3 | Chest pain: Week 6 | Chest pain: Week 9 | Chest pain: Week 12 | Chest pain: Week 15 | Chest pain: Week 18 | Chest pain: Week 21 | Chest pain: Week 24 | Chest pain: Week 27 | Chest pain: Week 30 | Chest pain: Week 33 | Chest pain: Week 36 | Chest pain: Week 39 | Chest pain: Week 42 | Chest pain: Week 45 | Chest pain: Week 48 | Chest pain: Week 51 | Chest pain: Week 54 | Chest pain: Week 57 | Chest pain: Week 60 | Chest pain: Week 63 | Chest pain: Week 66 | Chest pain: Week 69 | Chest pain:Post treatment efficacy visit 1 | Chest pain: Post treatment efficacy visit 2 | Chest pain: 7 days post disease progression | Chest pain: 28 days post disease progression | Coughing: Week 3 | Coughing: Week 6 | Coughing: Week 9 | Coughing: Week 12 | Coughing: Week 15 | Coughing: Week 18 | Coughing: Week 21 | Coughing: Week 24 | Coughing: Week 27 | Coughing: Week 30 | Coughing: Week 33 | Coughing: Week 36 | Coughing: Week 39 | Coughing: Week 42 | Coughing: Week 45 | Coughing: Week 48 | Coughing: Week 51 | Coughing: Week 54 | Coughing: Week 57 | Coughing: Week 60 | Coughing: Week 63 | Coughing: Week 66 | Coughing: Week 69 | Coughing: Post treatment efficacy visit 1 | Coughing: Post treatment efficacy visit 2 | Coughing: 7 days post disease progression | Coughing: 28 days post disease progression | Dyspnea: Week 3 | Dyspnea: Week 6 | Dyspnea: Week 9 | Dyspnea: Week 12 | Dyspnea: Week 15 | Dyspnea: Week 18 | Dyspnea: Week 21 | Dyspnea: Week 24 | Dyspnea: Week 27 | Dyspnea: Week 30 | Dyspnea: Week 33 | Dyspnea: Week 36 | Dyspnea: Week 39 | Dyspnea: Week 42 | Dyspnea: Week 45 | Dyspnea: Week 48 | Dyspnea: Week 51 | Dyspnea: Week 54 | Dyspnea: Week 57 | Dyspnea: Week 60 | Dyspnea: Week 63 | Dyspnea: Week 66 | Dyspnea: Week 69 | Dyspnea: Post treatment efficacy visit 1 | Dyspnea: Post treatment efficacy visit 2 | Dyspnea: 7 days post disease progression | Dyspnea: 28 days post disease progression |
|---|
| Randomized Part: Canakinumab + Docetaxel | -2.2 | 0.4 | 0.5 | 1.1 | 0.7 | 0.7 | 2.5 | 1.9 | 2.9 | 3.7 | -5.1 | -9.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | -11.1 | 0.0 | 0.0 | 0.0 | 0.0 | 11.1 | 5.4 | 14.8 | 0.0 | 3.0 | 2.6 | 4.8 | 2.0 | -1.3 | -4.2 | -1.0 | -4.3 | -5.6 | 2.6 | 12.1 | 3.3 | 6.7 | 0.0 | 11.1 | 16.7 | 16.7 | -8.3 | 0.0 | 0.0 | -16.7 | 0.0 | 0.0 | -22.2 | -1.1 | -3.7 | 4.8 | 4.4 | 4.8 | 7.4 | 6.5 | 10.2 | 8.9 | 7.9 | 10.1 | 8.0 | 13.7 | 12.1 | 14.4 | 20.0 | 20.6 | 20.4 | 22.2 | 22.2 | 19.4 | 25.9 | 18.5 | -11.1 | -22.2 | 16.7 | -3.7 | 5.0 | 3.7 |
Randomized Part: AUClast of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT03626545)
Timeframe: Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
| Intervention | hour*nanogram/miliLiter (h*ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 4 Day 1 |
|---|
| Randomized Part: Canakinumab + Docetaxel | 2530 | 2210 |
,| Randomized Part: Placebo + Docetaxel | 1790 | 1530 |
Safety run-in Part: Time of Maximum Plasma Concentration (Tmax) of Canakinumab
"Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.~Actual recorded sampling times were considered for the calculations." (NCT03626545)
Timeframe: Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
| Intervention | Hours (h) (Median) |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 169 |
Safety run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)
Percentage of participants with DLTs. A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first 42 days of docetaxel and canakinumab treatment. (NCT03626545)
Timeframe: During the first 42 days of dosing
| Intervention | Participants (Count of Participants) |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 1 |
All Collected Deaths
"Pre-treatment deaths were collected from screening to the first day of treatment, for a maximum duration of 28 days.~On-treatment deaths due to any cause were collected from first dose of study treatment to 130 days after the last dose of study treatment.~Post-treatment survival follow-up deaths were collected from day 131 after last dose of study treatment to end of study.~All deaths refer to the sum of pre-treatment, on-treatment and post-treatment deaths." (NCT03626545)
Timeframe: Pre-treatment: up to 28 days before Day 1;On-treatment: up to approximately 10 months (safety run-in) or 25 months (randomized); post-treatment survival follow-up deaths: Up to approximately 16 months (safety run in) or 25 months (randomized)
| Intervention | Participants (Count of Participants) |
|---|
| Pre-treatment deaths | On-treatment deaths | Post-treatment survival follow-up deaths | All deaths |
|---|
| Randomized Part: Canakinumab + Docetaxel | 0 | 45 | 40 | 85 |
,| Randomized Part: Placebo + Docetaxel | 1 | 37 | 38 | 76 |
,| Safety run-in Part: Canakinumab+Docetaxel | 0 | 6 | 2 | 8 |
Safety run-in Part: Tmax of Docetaxel
"Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.~Actual recorded sampling times were considered for the calculations." (NCT03626545)
Timeframe: Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
| Intervention | Hour (hr) (Median) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 1.08 | 1.00 |
Safety run-in Part: AUClast of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT03626545)
Timeframe: Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
| Intervention | Hour *nanogram/miliLiter (hr*ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 884 | 2120 |
Randomized Part: Tmax of Docetaxel
"Venous whole blood samples were collected for pharmacokinetics characterization. Tmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics.~Actual recorded sampling times were considered for the calculations." (NCT03626545)
Timeframe: Cycle 1 Day 1 and Cycle 4 Day 1 at pre-infusion, end of infusion, and 2, 4 and 6 hours post-dose. Each cycle is 21 days
| Intervention | Hour (Median) |
|---|
| Cycle 1 Day 1 | Cycle 4 Day 1 |
|---|
| Randomized Part: Canakinumab + Docetaxel | 1.09 | 1.15 |
,| Randomized Part: Placebo + Docetaxel | 1.10 | 1.08 |
Disease Control Rate (DCR)
"DCR is defined as the percentage of participants with CR or PR or with stable disease (SD) as per investigator assessment according to RECIST 1.1 criteria. The 95% CIs were computed using Clopper and Pearson 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." (NCT03626545)
Timeframe: Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
| Intervention | Percentage of participants (Number) |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 62.5 |
| Randomized Part: Canakinumab + Docetaxel | 65.8 |
| Randomized Part: Placebo + Docetaxel | 61.5 |
Duration of Response (DOR)
"DOR is defined as the time from first documented response of CR or PR to date of first documented progression or death, by investigator's assessment according to RECIST 1.1 criteria. The DOR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group.~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." (NCT03626545)
Timeframe: From first documented response of CR or PR to date of first documented progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 10 months for the safety run-in and 18 months for the randomized)
| Intervention | Months (Median) |
|---|
| Randomized Part: Canakinumab + Docetaxel | 4.14 |
| Randomized Part: Placebo + Docetaxel | 5.42 |
Overall Response Rate (ORR)
"ORR is defined as the percentage of participants with confirmed best overall response of complete response (CR) or partial response (PR), as per investigator's assessment by RECIST 1.1. The 95% confidence intervals (CIs) were computed using Clopper and Pearson 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." (NCT03626545)
Timeframe: Through final analysis data cutoff date of 08-Jan-2021 (assessed up to approx. 10 months for the safety run-in part and 18 months for the randomized part)
| Intervention | Percentage of participants (Number) |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 0.0 |
| Randomized Part: Canakinumab + Docetaxel | 15.0 |
| Randomized Part: Placebo + Docetaxel | 13.7 |
Randomized Part: Canakinumab ADA Incidence On-treatment
ADA incidence on-treatment was calculated as the percentage of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer) (NCT03626545)
Timeframe: Pre-dose at Cycle 1 Day 1, Cycle 4 Day 1, Cycle 6 Day 1, Cycle 12 Day 1 , end of treatment, and 130 days after end of treatment through final analysis data cutoff date of 08-Jan-2021 (assessed up to 18 months). Each cycle is 21 days
| Intervention | Participants (Count of Participants) |
|---|
| Randomized Part: Canakinumab + Docetaxel | 0 |
Randomized Part: Canakinumab Antidrug Antibodies (ADA) at Baseline
ADA prevalence at baseline was calculated as the percentage of participants who had an ADA positive result at baseline (NCT03626545)
Timeframe: Baseline
| Intervention | Participants (Count of Participants) |
|---|
| Randomized Part: Canakinumab + Docetaxel | 1 |
Randomized Part: Overall Survival (OS)
OS is defined as the time from randomization to date of death due to any cause. The OS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a subject was not known to have died, then OS was censored at the latest date the subject was known to be alive (on or before the cut-off date). (NCT03626545)
Timeframe: From randomization until death or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approximately (approx.) 18 months)
| Intervention | Months (Median) |
|---|
| Randomized Part: Canakinumab + Docetaxel | 10.55 |
| Randomized Part: Placebo + Docetaxel | 11.30 |
Safety run-in Part: Cmax of Docetaxel
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of docetaxel was calculated from docetaxel plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT03626545)
Timeframe: Cycle 1 Day 1 and Cycle 2 Day 1 at pre-infusion, end of infusion, and 2, 4, 6 and 8 hours post-dose. Each cycle is 21 days
| Intervention | nanogram/miliLiter (ng/mL) (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 476 | 1630 |
Randomized Part: Progression-Free Survival (PFS)
"PFS is defined as the time from randomization to the date of the first documented radiological progression by investigator assessment according to RECIST 1.1 response criteria or death due to any cause.~The PFS distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. If a participant did not have disease progression or die at the analysis cut-off date, PFS was censored at the date of last adequate tumor assessment." (NCT03626545)
Timeframe: From randomization until disease progression, death or final analysis data cutoff date (08-Jan-2021) whichever comes first (assessed up to approx. 18 months)
| Intervention | Months (Median) |
|---|
| Randomized Part: Canakinumab + Docetaxel | 4.17 |
| Randomized Part: Placebo + Docetaxel | 4.21 |
Randomized Part: Time to Response (TTR)
"TTR is defined as the time from the date of randomization to the date of first documented response of either CR or PR, by investigator's assessment according to RECIST 1.1 criteria. The TTR distribution was estimated using the Kaplan-Meier method and associated 95% confidence intervals were calculated for each treatment group. Subjects without a confirmed CR or PR at the time of the analysis cut-off date were censored at the study-maximum follow-up time for subjects with a PFS event (i.e., disease progression or death due to any cause), or at the date of the last adequate tumor assessment for subjects without a PFS event.~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." (NCT03626545)
Timeframe: From randomization until first documented response or final analysis data cutoff date (08-Jan-2021) whichever comes first (up to approx. 18 months)
| Intervention | Months (Median) |
|---|
| Randomized Part: Canakinumab + Docetaxel | NA |
| Randomized Part: Placebo + Docetaxel | NA |
Safety run-in Part: Area Under the Plasma Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUClast) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. AUClast of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT03626545)
Timeframe: Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
| Intervention | hour*microgram/mililiter (hr*ug/mL) (Geometric Mean) |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 5470 |
Safety run-in Part: Maximum Plasma Concentration (Cmax) of Canakinumab
Venous whole blood samples were collected for pharmacokinetics characterization. Cmax of canakinumab was calculated from canakinumab plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. (NCT03626545)
Timeframe: Cycle 1 Day 1 at pre-dose and end of infusion and 24, 48, 168 and 336 hours (h) post-infusion. Each cycle is 21 days
| Intervention | microgram/milliliter (ug/mL) (Geometric Mean) |
|---|
| Safety run-in Part: Canakinumab+Docetaxel | 13.4 |
Recurrence Free Survival (RFS)
No evidence of tumor recurrence or disease progression (NCT03636256)
Timeframe: At Months 6, 9, and 12
| Intervention | Months (Mean) |
|---|
| Non-Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort | 5.1 |
| Non-Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort | 6.7 |
| Non-Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort | 4.7 |
| Non-Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort | 9.6 |
Disease Progression
Disease progression at Day 45 derived from cytology and biopsy assessments (NCT03636256)
Timeframe: Day 45
| Intervention | Participants (Count of Participants) |
|---|
| Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort | 2 |
| Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort | 1 |
| Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort | 0 |
| Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort | 1 |
| Muscle Invasive Bladder Cancer Subset (Group 2 Subset) - 3.75/mg/mL NanoDoce Injection | 0 |
Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)
Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs. (NCT03636256)
Timeframe: Up to End of Treatment (Month 6 for Group 1 and Group 2 Subset, and Day 45 for Group 2)
| Intervention | Participants (Count of Participants) |
|---|
| Non-Muscle Invasive Bladder Cancer (Group 1) 0.75 mg/mL | 3 |
| Non-Muscle Invasive Bladder Cancer (Group 1) 1.5 mg/mL | 3 |
| Non-Muscle Invasive Bladder Cancer (Group 1) 2.5 mg/mL | 3 |
| Non-Muscle Invasive Bladder Cancer (Group 1) 3.75 mg/mL | 9 |
| Muscle Invasive Bladder Cancer (Group 2) Subset 3.75 mg/mL | 1 |
| Muscle Invasive Bladder Cancer (Group 2) 0.75 mg/mL | 5 |
| Muscle Invasive Bladder Cancer (Group 2) 1.5 mg/mL | 2 |
| Muscle Invasive Bladder Cancer (Group 2) 2.5 mg/mL | 1 |
| Muscle Invasive Bladder Cancer (Group 2) 3.75 mg/mL | 6 |
Maximum Plasma Concentration (Cmax) of Spartlizumab
The maximum (peak) observed plasma concentration after single dose administration. Cmax was calculated using non-compartmental methods. (NCT03647488)
Timeframe: Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days
| Intervention | microgram/milliliter (μg/mL) (Geometric Mean) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 138 |
All Collected Deaths
"On-treatment deaths due to any cause were collected from first dose of study medication to 150 days after the last dose of spartalizumab, or 30 days after the last dose of capmatinib, whichever is later, up to a maximum duration of approximately 1.7 years.~Total deaths were collected from first dose of study treatment until end of post-treatment efficacy or survival follow, up to maximum duration of approximately 1.7 years" (NCT03647488)
Timeframe: On-treatment deaths: up to approximately 1.7 years. All deaths: up to approximately 1.7 years
| Intervention | Participants (Number) |
|---|
| Total Deaths | Deaths on-treatment |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 12 | 5 |
Run-in Part: Percentage of Participants With Adverse Events (AEs)
"Percentage of participants with AEs, including changes from baseline in vital signs and laboratory results qualifying and reported as AEs.~AEs were assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v5.0: Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences; Grade 5: Death" (NCT03647488)
Timeframe: From the day of the first dose of study medication to 150 days after the last dose of spartalizumab, or 30 days after the last dose of capmatinib (whichever is later) up to maximum duration of approximately 1.7 years
| Intervention | Participants (Count of Participants) |
|---|
| AEs- All grades | AEs- Grade ≥3 | Treatment-related AEs- All grades | Treatment related AEs- Grade ≥3 | Serious AEs (SAEs)- All grades | SAEs- Grade ≥3 | Treatment-related SAEs- All grades | Treatment-related SAEs- Grade ≥3 | Fatal SAEs- All grades | Fatal SAEs- Grade ≥3 | AEs leading to discontinuation- All grades | AEs leading to discontinuation- Grade ≥3 | Treatment-related AEs leading to discontinuation- All grades | Treatment-related AEs leading to discontinuation- Grade ≥3 | AEs leading to dose adjustment/interruption- All grades | AEs leading to dose adjustment/interruption- Grade ≥3 | AEs requiring additional therapy- All grades | AEs requiring additional therapy- Grade ≥3 |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 18 | 11 | 14 | 1 | 10 | 7 | 3 | 0 | 1 | 1 | 5 | 3 | 3 | 1 | 9 | 5 | 16 | 8 |
Run-in Part: Percentage of Participants With at Least One Dose Interruption
Percentage of participants with at least one dose interruption. Dose interruptions were allowed for capmatinib and spartalizumab. (NCT03647488)
Timeframe: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Capmatinib | Spartalizumab |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 8 | 3 |
Run-in Part: Relative Dose Intensity Received by Participants
The relative dose intensity of capmatinib and spartalizumab is computed as the ratio of dose intensity and planned dose intensity, multiplied by 100. (NCT03647488)
Timeframe: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
| Intervention | Percentage of dose received (Median) |
|---|
| Capmatinib | Spartalizumab |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 99.6 | 100.0 |
Objective Response Rate (ORR) Based on RECIST 1.1 and as Per Investigator Assessment
"ORR is defined as the percentage of subjects with best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and as per investigator assessment.~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.~ORR results for randomized part are not available because randomized part never started." (NCT03647488)
Timeframe: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)
| Intervention | Percentage of participants (Number) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 0 |
Progression Free Survival (PFS)
"PFS is defined as the time from the date of start of treatment to the date of the first documented radiological progression or death due to any cause. For participants who had not progressed or died at the analysis cut-off date, PFS was censored at the date of the last adequate tumor evaluation date. An adequate tumour assessment is a tumour assessment with an overall response other than unknown.~Progression is defined using RECIST 1.1 and as per investigator assessment as 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. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.~PFS results for randomized part are not available because randomized part never started." (NCT03647488)
Timeframe: From start of treatment until the first documented radiological progression or death, whichever comes first, assessed up to 68 weeks (run-in part)
| Intervention | Months (Median) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 1.9 |
Run-in Part: Percentage of Participants With at Least One Dose Reduction.
Percentage of participants with at least one dose reduction. Dose reductions were only allowed for capmatinib (NCT03647488)
Timeframe: From the day of the first dose of study medication to end of treatment, assessed up to maximum duration of 68 weeks
| Intervention | Participants (Count of Participants) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 6 |
Maximum Plasma Concentration (Cmax) of Capmatinib
The maximum (peak) observed plasma concentration after single dose administration. Cmax was calculated using non-compartmental methods. (NCT03647488)
Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
| Intervention | nanogram/milliliter (ng/mL) (Geometric Mean) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 3260 |
Spartalizumab ADA Incidence On-treatment
ADA incidence on treatment was calculated as the proportion of participants who were treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer) (NCT03647488)
Timeframe: Predose at Cycle (C)1 Day (D)1, C2D1, C3D1, C4D1, C6D1, C8D1, C10D1, C12D1, thereafter every 6 cycles until discontinuation, and end of treatment (EOT), 30-day and 150-day after EOT
| Intervention | Participants (Count of Participants) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 3 |
Spartalizumab Antidrug Antibodies (ADA) Prevalence at Baseline
ADA prevalence at baseline was calculated as the proportion of participants who had an ADA positive result at baseline (NCT03647488)
Timeframe: Cycle 1 Day 1 at predose. Each Cycle is 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 3 |
AUClast of Capmatinib
AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated using non-compartmental methods. (NCT03647488)
Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
| Intervention | nanogram*hour/milliliter (ng*hr/mL) (Geometric Mean) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 11500 |
Time to Reach Maximum (Tmax) Plasma Concentration of Spartlizumab
Tmax is the time to reach maximum (peak) plasma concentration of spartlizumab after single dose administration (time). Tmax was calculated using non-compartmental methods. (NCT03647488)
Timeframe: Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days
| Intervention | hour (h) (Median) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 1.13 |
Time to Reach Maximum (Tmax) Plasma Concentration of Capmatinib
Tmax is the time to reach maximum (peak) plasma concentration of capmatinib after single dose administration (time). Tmax was calculated using non-compartmental methods. (NCT03647488)
Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
| Intervention | hour (h) (Median) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 1.42 |
Disease Control Rate (DCR) Based on RECIST 1.1 and as Per Investigator Assessment
"DCR is defined as the percentage of subjects with best overall response of CR or PR or stable disease based on RECIST 1.1 and as per investigator assessment.~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.~Stable disease: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.~DCR results for randomized part are not available because randomized part never started." (NCT03647488)
Timeframe: From start of treatment until end of treatment, assessed up to 68 weeks (run-in part)
| Intervention | Percentage of participants (Number) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 27.8 |
AUCtau of Spartlizumab
AUCtau is the area under the plasma concentration-time curve from time zero to the end of the dosing interval Tau. AUCtau was calculated using non-compartmental methods. (NCT03647488)
Timeframe: Cycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days
| Intervention | microgram*day/milliliter (μg*day/mL) (Geometric Mean) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 2110 |
AUCtau of Capmatinib
AUCtau is the area under the plasma concentration-time curve from time zero to the end of the dosing interval Tau. AUCtau was calculated using non-compartmental methods. (NCT03647488)
Timeframe: Cycle 3 day 1 at predose, 0.5 hours (h), 1h, 2h, 4h and 8h postdose. Each Cycle is 28 days
| Intervention | nanogram*hour/milliliter (ng*hr/mL) (Geometric Mean) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 12800 |
AUClast of Spartlizumab
AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. AUClast was calculated using non-compartmental methods. (NCT03647488)
Timeframe: CCycle 3 day 1 at predose and 1 hour postdose (up to 1.53 hours postdose), cycle 3 day 4 (=72 hours postdose), cycle 3 day 8 (=168 hours postdose) and cycle 3 day 15 (=336 hours postdose). Each Cycle is 28 days
| Intervention | microgram*day/milliliter (μg*day/mL) (Geometric Mean) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 1720 |
Run-in Part: Percentage of Participants With Dose Limiting Toxicities (DLTs)
A DLT was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease progression, inter-current illness, or concomitant medications that met certain criteria as defined in the protocol. (NCT03647488)
Timeframe: From the day of the first dose of study medication up to 56 days
| Intervention | Participants (Count of Participants) |
|---|
| Run-in Part: Capmatinib + Spartalizumab | 1 |
Change From Baseline in Temperature-Part 1
Temperature was measured after 5 minutes of rest for the participant. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Celsius (C) (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 36.5 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 36.64 | 0.04 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 36.9 | -0.3 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 36.8 | 0.04 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 36.6 | 0.2 |
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)-Part 1
SBP and DBP were measured after 5 minutes of rest for the participant. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Millimeters of mercury (mmHg) (Mean) |
|---|
| SBP, Baseline (Day 1) | SBP, Week 4 | DBP, Baseline (Day 1) | DBP, Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 104 | 16 | 73 | 4 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 127.5 | -0.27 | 76.25 | -2.8 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 128 | -12 | 79 | -3 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 128 | -10 | 83.4 | -5 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 133.67 | -12 | 74.67 | -4 |
Change From Baseline in Specific Gravity of Urine-Part 1
Urine samples were collected to assess change from baseline in specific gravity of urine. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Ratio (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 1.015 | 0.005 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 1.0159 | -0.0005 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 1.0204 | -0.0055 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 1.021 | 0.0013 |
Change From Baseline in Specific Gravity of Urine-Part 1
Urine samples were collected to assess change from baseline in specific gravity of urine. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Ratio (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 1.02 |
Change From Baseline in Respiratory Rate-Part 1
Respiratory rate was measured after 5 minutes of rest for the participant. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | breaths/ minute (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 18 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 16.75 | 0.07 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 18 | -2 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 17.6 | 0 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 16 | 2 |
Change From Baseline in Pulse Rate-Part 1
Pulse rate was measured after 5 minutes of rest for the participant. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | beats/minute (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 81 | 1 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 76.56 | 8.07 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 83 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 91.6 | -2.4 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 79.67 | 5 |
Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1
Urine samples were collected to assess change from baseline in pH of urine. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | pH (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 6.5 | -0.5 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 6.16 | -0.24 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 6 | 0.5 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 5.33 | -0.33 |
Change From Baseline in Oxygen Saturation-Part 1
Oxygen saturation was measured using pulse oximeter after 5 minutes of rest for the participant. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Percentage (%) of Oxygen (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 96 | 2 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 97.63 | -0.2 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 95 | 5 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 95.6 | 0.8 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 96 | 0 |
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1
Blood samples were collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet counts. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Basophils, Baseline (Day 1) | Eosinophils, Baseline (Day 1) | Lymphocytes, Baseline (Day 1) | Monocytes, Baseline (Day 1) | Neutrophils, Baseline (Day 1) | Platelets, Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0.00 | 0.1 | 1.5 | 0.3 | 3.9 | 325 |
Change From Baseline in Neutrophil, Lymphocyte, Monocyte, Eosinophil, Basophil and Platelet Count-Part 1
Blood samples were collected to assess change from Baseline in neutrophil, lymphocyte, monocyte, eosinophil, basophil and platelet counts. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | 10^9 cells/liter (Mean) |
|---|
| Basophils, Baseline (Day 1) | Basophils, Week 4 | Eosinophils, Baseline (Day 1) | Eosinophils, Week 4 | Lymphocytes, Baseline (Day 1) | Lymphocytes, Week 4 | Monocytes, Baseline (Day 1) | Monocytes, Week 4 | Neutrophils, Baseline (Day 1) | Neutrophils, Week 4 | Platelets, Baseline (Day 1) | Platelets, Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0.00 | 0.00 | 0.3 | 0.4 | 1 | 0.4 | 0.4 | 0 | 4 | 0.3 | 196 | -1 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 0.039 | 0.007 | 0.2 | 0.07 | 0.92 | 0.01 | 0.738 | 0.038 | 11.32 | -8.95 | 266.3 | 31.3 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0.05 | 0 | 0.35 | 0.03 | 0.9 | 0.23 | 0.8 | 0.05 | 4.38 | 0.93 | 250.6 | 8.6 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0.01 | 0.005 | 0.08 | 0.06 | 1.25 | -0.38 | 1.255 | -0.215 | 6.2 | -0.9 | 229.7 | -8.7 |
Change From Baseline in Hemoglobin Level-Part 1
Blood samples were collected to assess change from baseline in hemoglobin level. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | grams/liter (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 125 | 5 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 111.5 | -0.7 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 123.4 | -5.8 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 125 | 0.3 |
Change From Baseline in Hemoglobin Level-Part 1
Blood samples were collected to assess change from baseline in hemoglobin level. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | grams/liter (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 134 |
Change From Baseline in Hematocrit Level-Part 1
Blood samples were collected to assess change from baseline in hematocrit level. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | fraction of 1 (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0.38 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 0.3421 | -0.0039 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0.385 | -0.0202 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0.3937 | -0.0017 |
Change From Baseline in Hematocrit Level-Part 1
Blood samples were collected to assess change from baseline in hematocrit level. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | fraction of 1 (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0.4 |
Change From Baseline in Free Triiodothyronine (T3)-Part 1
Blood samples were collected to assess change from Baseline in free T3. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Picomoles per liter (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 3.5 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 3.88 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 3.6 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 2.75 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 4.47 |
Change From Baseline in Free Thyroxine (T4)-Part 1
Blood samples were collected to assess change from baseline in free T4. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Picomoles per liter (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 13.84 | 2.57 |
Change From Baseline in Free Thyroxine (T4)-Part 1
Blood samples were collected to assess change from baseline in free T4. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | Picomoles per liter (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 10 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 15.98 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 11 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 12.43 |
Change From Baseline in Erythrocytes Count-Part 1
Blood samples were collected to assess change from baseline in Erythrocytes count. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | 10^12 cells/liter (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 4.2 | 0.13 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 3.76 | 0.016 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 4.328 | -0.216 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 4.673 | 0.04 |
Change From Baseline in Erythrocytes Count-Part 1
Blood samples were collected to assess change from baseline in Erythrocytes count. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | 10^12 cells/liter (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 4.65 |
Change From Baseline in Creatinine and Bilirubin Levels-Part 1
Blood samples were collected to assess change from baseline in creatinine and bilirubin levels. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | micromoles/ Liter (Mean) |
|---|
| Bilirubin, Baseline (Day 1) | Bilirubin, Week 4 | Creatinine, Baseline (Day 1) | Creatinine, Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 5 | -1 | 59000 | 1000 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 6.5 | -0.4 | 93 | -2.9 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 6.1 | 2.2 | 31636.7 | -1798.9 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 6.1 | -1.1 | 73.5 | 3.1 |
Change From Baseline in Creatinine and Bilirubin Levels-Part 1
Blood samples were collected to assess change from baseline in creatinine and bilirubin levels. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | micromoles/ Liter (Mean) |
|---|
| Bilirubin, Baseline (Day 1) | Creatinine, Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 7 | 63000 |
Change From Baseline in Amylase and Lipase Levels-Part 1
Blood samples were collected to assess change from baseline in amylase and lipase levels. (NCT03693612)
Timeframe: Baseline (Day 1) and week 4
| Intervention | Units/milliliter (Mean) |
|---|
| Amylase, Baseline (Day 1) | Amylase, Week 4 | Lipase, Baseline (Day 1) | Lipase, Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 48 | -2 | 28 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 51.5 | -3.5 | 34.6 | 6.1 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 50.2 | -5.3 | 50.8 | 1.5 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 40 | -5 | 54.7 | -13 |
Change From Baseline in Amylase and Lipase Levels-Part 1
Blood samples were collected to assess change from baseline in amylase and lipase levels. (NCT03693612)
Timeframe: Baseline (Day 1) and week 4
| Intervention | Units/milliliter (Mean) |
|---|
| Amylase, Baseline (Day 1) | Lipase, Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 50 | 23 |
Change From Baseline in Albumin and Total Protein Levels-Part 1
Blood samples were collected to assess change from Baseline in albumin and total protein levels. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | grams/Liter (Mean) |
|---|
| Albumin, Baseline (Day 1) | Albumin, Week 4 | Protein, Baseline (Day 1) | Protein, Week 4 |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 37.9 | -2.1 | 72.1 | 1.4 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 36 | 0 | 66.7 | 3.3 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 36.7 | -0.7 | 73 | 0 |
Change From Baseline in Albumin and Total Protein Levels-Part 1
Blood samples were collected to assess change from Baseline in albumin and total protein levels. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | grams/Liter (Mean) |
|---|
| Albumin, Baseline (Day 1) | Albumin, Week 4 | Protein, Baseline (Day 1) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 41 | 0 | 71 |
Change From Baseline in Albumin and Total Protein Levels-Part 1
Blood samples were collected to assess change from Baseline in albumin and total protein levels. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | grams/Liter (Mean) |
|---|
| Albumin, Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 40 |
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1
Blood samples were collected to assess change from baseline in ALT, AST ALP, LDH levels. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | International Units/milliliter (Mean) |
|---|
| ALP, Baseline (Day 1) | ALP, Week 4 | ALT, Baseline (Day 1) | ALT, Week 4 | AST, Baseline (Day 1) | AST, Week 4 | LDH, Baseline (Day 1) | LDH, Week 4 |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 120.2 | 36.2 | 18.2 | 7.4 | 21.9 | 12.9 | 239.9 | 42.9 |
,| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 53 | 2 | 18 | -2 | 32 | 0 | 325 | 127 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 307.4 | 55.8 | 24 | 8.2 | 24.6 | 10 | 228.8 | 11.4 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 121.5 | -18 | 26.7 | -4.7 | 23.7 | -7 | 168 | 31.3 |
Change From Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH) Levels-Part 1
Blood samples were collected to assess change from baseline in ALT, AST ALP, LDH levels. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | International Units/milliliter (Mean) |
|---|
| ALP, Baseline (Day 1) | ALT, Baseline (Day 1) | AST, Baseline (Day 1) | LDH, Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 68 | 25 | 44 | 382 |
Overall Response Rate-Part 1
Overall response rate is defined as percentage of participants with confirmed complete response (Disappearance of all target lesions. Any pathological lymph nodes [whether target or non-target] must have reduction in short axis to <10 millimeter [mm]) or partial response (At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) at any time as per response evaluation criteria in solid tumors (RECIST) version 1.1. (NCT03693612)
Timeframe: Up to 4 years
| Intervention | Percentage of Participants (Number) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 6.3 |
Number of Participants With Dose Limiting Toxicities (DLTs)-Part 1
A DLT is considered by the investigator to be clinically relevant, attributed event within first 28 days of intervention meeting the following criteria of toxicity, Hematologic: Febrile neutropenia, Grade 4 neutropenia of greater than (>) 7 days in duration or requiring Granulocyte- Colony stimulating factor (G-CSF), Grade 4 anemia and Grade 3 thrombocytopenia with bleeding or Grade 4 thrombocytopenia; Non-hematologic: Grade 4 toxicity, Grade 3 pneumonitis, any greater than or equal to (≥) Grade 2 pneumonitis that does not resolve to less than or equal to (≤ ) Grade 1 within 3 days of the initiation of maximal supportive care, Grade 3 toxicity that does not resolve to Grade 1 or baseline within 3 days despite optimal supportive care and any Grade 2 ocular toxicity requiring systemic steroids, or any ≥ Grade 3 ocular toxicity. (NCT03693612)
Timeframe: Up to 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 1 |
Minimum Observed Plasma Concentration (Cmin) of Feladilimab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment. (NCT03693612)
Timeframe: Pre-dose, end of infusion and 4 hours post dose at Day 1
| Intervention | nanograms/ milliliter (Geometric Mean) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 462 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 348 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 3197 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 856.4 |
Maximum Observed Plasma Concentration (Cmax) of Feladilimab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment. (NCT03693612)
Timeframe: Pre-dose, end of infusion and 4 hours post dose at Day 1
| Intervention | nanograms/milliliter (Geometric Mean) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 2758 |
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 5965 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 2686.6 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 28340.9 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 6098.3 |
Disease Control Rate-Part 1
Disease control rate is defined as percentage of subjects with confirmed 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) or at least 18 weeks of stable disease (Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD) as per RECIST version 1.1. (NCT03693612)
Timeframe: Up to 4 years
| Intervention | Percentage of Participants (Number) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 33.3 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 12.5 |
Cmin of Tremelimumab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment. (NCT03693612)
Timeframe: Pre-dose, end of infusion and 4 hours post dose at Day 1
| Intervention | nanograms/ milliliter (Geometric Mean) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 6467 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 22466.3 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 5715.6 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 15084.9 |
Cmax of Tremelimumab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment. (NCT03693612)
Timeframe: Pre-dose, end of infusion and 4 hours post dose at Day 1
| Intervention | nanograms/milliliter (Geometric Mean) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 112312.1 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 93206.7 |
AUC(0-t) of Tremelimumab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment. (NCT03693612)
Timeframe: Pre-dose, end of infusion and 4 hours post dose at Day 1
| Intervention | nanograms*hours/milliLiter (Geometric Mean) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 18160725.7 |
Area Under the Plasma Concentration-time Curve (AUC[0-t]) of Feladilimab-Part 1
Blood samples were collected at indicated time points for pharmacokinetic assessment. (NCT03693612)
Timeframe: Pre-dose, end of infusion and 4 hours post dose at Day 1
| Intervention | nanograms*hours/milliLiter (Geometric Mean) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 545097.4 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 453561.5 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 4552653.1 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 1055659.5 |
Change From Baseline in Potential of Hydrogen (pH) of Urine-Part 1
Urine samples were collected to assess change from baseline in pH of urine. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | pH (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 7 |
Number of Participants With AEs, SAEs, AESIs According to Severity - Part 1
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for ≤24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE. (NCT03693612)
Timeframe: Up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1: AEs | Grade 2: AEs | Grade 3: AEs | Grade 4: AEs | Grade 5: AEs | Grade 1: SAEs | Grade 2: SAEs | Grade 3: SAEs | Grade 4: SAEs | Grade 5: SAEs | Grade 1: AESI | Grade 2: AESI | Grade 3: AESI | Grade 4: AESI | Grade 5: AESI |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 4 | 4 | 6 | 1 | 1 | 0 | 1 | 3 | 1 | 1 | 3 | 2 | 1 | 1 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 | 1 | 3 | 1 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 2 | 0 | 0 | 0 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Electrocardiogram (ECG) Findings
Single 12-lead ECG was obtained using an automated ECG machine. ECG findings were categorized as: normal, abnormal - clinically significant (CS), or abnormal - not clinically significant (NCS), as determined by the investigator. (NCT03693612)
Timeframe: Baseline (Pre dose, Day 1) and up to 4 Years
| Intervention | Participants (Count of Participants) |
|---|
| Baseline (Pre dose, Day 1)72491653 | Baseline (Pre dose, Day 1)72491654 | Baseline (Pre dose, Day 1)72491655 | Baseline (Pre dose, Day 1)72491656 | Baseline (Pre dose, Day 1)72491657 | Worst case Post-Baseline72491653 | Worst case Post-Baseline72491654 | Worst case Post-Baseline72491655 | Worst case Post-Baseline72491656 | Worst case Post-Baseline72491657 |
|---|
| Normal | Abnormal CS | Abnormal NCS |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 1 |
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 1 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 6 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 1 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 3 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 2 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 10 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 0 |
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 |
| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 |
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 1 |
| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 2 |
Number of Participants With Severe- AEs/SAEs/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
The number of participants with severe- AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized. (NCT03693612)
Timeframe: Up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Any Severe Aes-Dose Modification | Any Severe Aes-Dose Delay | Any Severe Aes-Dose Withdrawal | Any Severe SAEs-Dose Modification | Any Severe SAEs-Dose Delay | Any Severe SAEs-Dose Withdrawal | Any Severe DLTs-Dose Modification | Any Severe DLTs-Dose Delay | Any Severe DLTs-Dose Withdrawal |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 0 | 4 | 3 | 0 | 1 | 2 | 0 | 1 | 1 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 | 3 | 1 | 0 | 1 | 1 | 0 | 0 | 0 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Number of Participants With DLTs According to Severity-Part 1
The severity of all toxicities were graded using the National Cancer Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 5.0. Grade 1: Mild reaction; infusion interruption not indicated; intervention not indicated; Grade 2: Requires therapy or infusion interruption but responds promptly to symptomatic treatment or prophylactic medications indicated for ≤24 hours; Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion) or recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae; Grade 4: Life-threatening; pressor or ventilatory support indicated; Grade 5: Death related to AE. (NCT03693612)
Timeframe: Up to 28 days
| Intervention | Participants (Count of Participants) |
|---|
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 0 | 0 | 1 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 |
Number of Participants With Anti-drug Antibodies Against Tremelimumab-Part 1
Serum samples were collected and tested for the presence of antibodies to tremelimumab. (NCT03693612)
Timeframe: Pre-dose at Week 1, 4, 7, 10 and 13
| Intervention | Participants (Count of Participants) |
|---|
| Week 1 | Week 4 | Week 7 | Week 10 | Week 13 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 0 | 2 | 1 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 | 0 | 1 | 1 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 | 1 | 0 | 0 | 0 |
Number of Participants With Anti-drug Antibodies Against Feladilimab-Part 1
Serum samples were collected and tested for the presence of antibodies to feladilimab. (NCT03693612)
Timeframe: Pre-dose at Week 4, 7, 10 and 13
| Intervention | Participants (Count of Participants) |
|---|
| Week 4 | Week 7 | Week 10 | Week 13 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 5 | 2 | 1 | 1 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 1 | 1 | 1 | 0 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 |
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESI)-Part 1
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. 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 disability/incapacity; is a congenital anomaly/birth defect and important medical events may jeopardize the subject or may require medical or surgical intervention/SOC to prevent one of the other outcomes mentioned before. AESIs are defined as events of potential immunologic etiology, including immune related AEs. (NCT03693612)
Timeframe: Up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| AEs | SAEs | AESIs |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 1 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 16 | 6 | 7 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 1 | 0 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 5 | 3 | 2 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 3 | 3 | 0 |
Number of Participants With Abnormal Urinalysis Parameters-Part 1
The dipstick test gives positive or negative results for protein, ketones, occult blood and glucose in urine. Positive test results were considered as abnormal. Number of participants with positive test results have been summarized. (NCT03693612)
Timeframe: Week 4
| Intervention | Participants (Count of Participants) |
|---|
| Dip stick test for Glucose | Dip stick test for Protein | Dip stick test for Occult Blood | Dip stick test for Ketones |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 | 0 | 1 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 2 | 6 | 5 | 3 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 1 | 1 | 2 | 4 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 | 0 | 1 | 0 |
Number of Participant With AE/SAE/DLTs Leading to Dose Modifications/Delays/Withdrawals-Part 1
The number of participants with AE/SAE/DLTs leading to dose modifications/delays/withdrawals were summarized. (NCT03693612)
Timeframe: Up to 4 years
| Intervention | Participants (Count of Participants) |
|---|
| Any Aes-Dose Modification | Any Aes-Dose Delay | Any Aes-Dose Withdrawal | Any SAEs-Dose Modification | Any SAEs-Dose Delay | Any SAEs-Dose Withdrawal | Any DLTs-Dose Modification | Any DLTs-Dose Delay | Any DLTs-Dose Withdrawal |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 0 | 4 | 3 | 0 | 1 | 2 | 0 | 1 | 1 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 0 | 3 | 1 | 0 | 1 | 1 | 0 | 0 | 0 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1
Blood samples were collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | millimoles/Liter (Mean) |
|---|
| Glucose, Baseline (Day 1) | Calcium, Baseline (Day 1) | Potassium, Baseline (Day 1) | Sodium, Baseline (Day 1) | Urea, Baseline (Day 1) |
|---|
| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 7.3 | 2.24 | 4 | 140 | 3.3 |
Change From Baseline in Urea, Glucose, Potassium, Sodium and Calcium Levels-Part 1
Blood samples were collected to assess change in levels of urea, glucose, potassium, sodium and calcium from baseline. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | millimoles/Liter (Mean) |
|---|
| Glucose, Baseline (Day 1) | Glucose, Week 4 | Calcium, Baseline (Day 1) | Calcium, Week 4 | Potassium, Baseline (Day 1) | Potassium, Week 4 | Sodium, Baseline (Day 1) | Sodium, Week 4 | Urea, Baseline (Day 1) | Urea, Week 4 |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 6.7 | -0.3 | 2.37 | 0.15 | 4.3 | -0.3 | 138 | -1 | 3.4 | 1.5 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 6.397 | -0.11 | 2.33 | -0.028 | 4.22 | -0.01 | 137.1 | -1 | 6.92 | -0.51 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 6.09 | -0.365 | 2.325 | 0.137 | 4.18 | 0.04 | 137.2 | 0.2 | 6.36 | -1.37 |
,| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 5.897 | -0.848 | 2.397 | 0.05 | 4.3 | -0.03 | 137.3 | 0.7 | 7.36 | 1.08 |
Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1
Blood samples were collected to assess change from Baseline in TSH. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | milliUnits/Liter (Mean) |
|---|
| Baseline (Day 1) | Week 4 |
|---|
| Part 1: Feladilimab 80 mg + Tremelimumab 75 mg | 1.463 | -0.87 |
Change From Baseline in Thyroid Stimulating Hormone (TSH) or Thyrotropin-Part 1
Blood samples were collected to assess change from Baseline in TSH. (NCT03693612)
Timeframe: Baseline (Day 1) and Week 4
| Intervention | milliUnits/Liter (Mean) |
|---|
| Baseline (Day 1) |
|---|
| Part 1: Feladilimab (GSK3359609) 8 mg + Tremelimumab 75 mg | 0.79 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 225 mg | 2.211 |
,| Part 1: Feladilimab 24 mg + Tremelimumab 75 mg | 1.22 |
,| Part 1: Feladilimab 8 mg + Tremelimumab 225 mg | 1.856 |
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
| Intervention | months (Median) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 11.3 |
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.
| Intervention | percentage of participants (Number) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 100 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Number of patients had at least one adverse event of any grade | Number of patients had at least one grade 3 or greater adverse event | Number of patients had at least one grade 3 or greater treatment related adverse event | Number of patients having serious adverse event |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 6 | 6 | 6 | 3 |
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
| Intervention | months (Median) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 11.3 |
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.
| Intervention | percentage of participants (Number) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 40 |
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.
| Intervention | percentage of participants (Number) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 100 |
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
| Intervention | months (Median) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | NA |
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
| Intervention | months (Median) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 11.3 |
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.
| Intervention | percentage of participants (Number) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 40 |
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
| Intervention | months (Median) |
|---|
| Phase IIA : Atezolizumab + Carboplatin + Gemcitabine | 11.3 |
Number of Participants Who Had a Pathological Complete Response (pCR)
pCR is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy (ypT0/Tis ypN0). (NCT03742986)
Timeframe: up to 1 year
| Intervention | Participants (Count of Participants) |
|---|
| HER2-negative, Including TNBC or HR-positive | 1 |
| HER2-positive, Independent of HR Status | 3 |
Number of Participants Who Had a Pathological Complete Response (pCR)
pCR is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen, axillary nodes, or sentinel node identified after neoadjuvant chemotherapy (ypT0/Tis ypN0). (NCT03742986)
Timeframe: up to 16 weeks
| Intervention | Participants (Count of Participants) |
|---|
| HER2-negative, Including TNBC or HR-positive | 0 |
| HER2-positive, Independent of HR Status | 3 |
Prostate Specific Antigen Progression Free Survival (PSA-PFS)
Prostate Specific Antigen (PSA) will be measured every three months while on study. PSA Progression Free Survival (PSA-PSF) will be reported as the number of participants who have not demonstrated PSA progression by the end of the follow-up period. PSA progression is defined by meeting the following criteria: 1) an increase in PSA of greater than or equal to 25% from baseline or nadir, AND 2) an increase in PSA of at least 2 ng/dL, AND 3) the increase is confirmed at least 3 weeks later. This analysis was planned for up to 18 months following study enrollment, but the only participant enrolled on the study was only followed for 3 months. (NCT03827473)
Timeframe: Planned up to 18 months, but actual was 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (ADT, Docetaxel) | 1 |
Change in Quality of Life - PROMIS Fatigue
Quality of Life questionnaires will be done every 3 months while participants are on treatment. The scale used will be the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue scale. Total raw scores range from 7 to 35, with higher scores indicating a higher level of fatigue. (NCT03827473)
Timeframe: Planned for up to 18 months, but actual was 3 months
| Intervention | score on a scale (Number) |
|---|
| Baseline Score | Month 3 Score |
|---|
| Arm A (ADT, Docetaxel) | 10 | 16 |
Change in Quality of Life - FACT-P
The impact of abiraterone acetate and docetaxel on health related quality of life will be assessed every 3 months from screening to month 12 of treatment or follow-up. The scale used will be the Functional Assessment of Cancer Therapy-Prostate (FACT-P) scale. The total score ranges from 0 to 156, with higher scores indicating a higher quality of life. The primary endpoint was intended to be quality of life at 12 months, but since no participants completed 12 months of treatment/follow-up, scores at baseline and 3 months are reported instead. (NCT03827473)
Timeframe: Planned for up to one year, but actual was 3 months
| Intervention | score on a scale (Number) |
|---|
| Baseline Score | Month 3 Score |
|---|
| Arm A (ADT, Docetaxel) | 139.83 | 127 |
Prostate-specific Antigen (PSA) Response
PSA evaluations will occur every 3 months while on study. PSA response is defined as a reduction in PSA value of greater than or equal to 90% from baseline, reported as a count of participants who had a PSA response on the study. (NCT03827473)
Timeframe: Planned for up to 18 months, but actual was 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Arm A (ADT, Docetaxel) | 1 |
Change in Quality of Life - FACT/GOG-NTX
Quality of Life questionnaires will be done every 3 months while participants are on treatment. The scale used will be the Functional Assessment of Cancer Therapy (FACT)/Gynecologic Oncology Group (GOG)-Neurotoxicity (NTX) (FACT/GOG-NTX) scale (version 4). FACT/GOG-NTX total score ranges from 0 to 152, with higher scores indicating a higher quality of life. (NCT03827473)
Timeframe: Planned for up to 18 months, but actual was 3 months
| Intervention | score on a scale (Number) |
|---|
| Baseline Score | Month 3 Score |
|---|
| Arm A (ADT, Docetaxel) | 131.83 | 126 |
Time to Prostate-specific Antigen (PSA) Progression
"The time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of:~≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR~≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline~Time to PSA progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without PSA progression were censored at the last evaluable assessment." (NCT03834506)
Timeframe: Up to 36.5 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 6.9 |
| Placebo + Docetaxel | 7.0 |
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. An AE could therefore have been 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 experienced an AE is presented. (NCT03834506)
Timeframe: Up to approximately 30 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Docetaxel | 508 |
| Placebo + Docetaxel | 505 |
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression 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 progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. (NCT03834506)
Timeframe: Up to 36.5 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 12.4 |
| Placebo + Docetaxel | 11.2 |
Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST)
TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product-limit (Kaplan-Meier) method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received. (NCT03834506)
Timeframe: Up to approximately 28 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 10.7 |
| Placebo + Docetaxel | 10.4 |
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment. (NCT03834506)
Timeframe: Up to approximately 28 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 8.6 |
| Placebo + Docetaxel | 8.3 |
Prostate-specific Antigen (PSA) Response Rate
The Prostate-specific Antigen (PSA) response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response. The analysis was performed on participants who had baseline PSA measurements. (NCT03834506)
Timeframe: Up to 36.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab + Docetaxel | 44.5 |
| Placebo + Docetaxel | 45.7 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. (NCT03834506)
Timeframe: Up to 36.5 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 19.6 |
| Placebo + Docetaxel | 19.0 |
Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review
DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 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. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for ≥6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment. (NCT03834506)
Timeframe: Up to 36.5 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 6.3 |
| Placebo + Docetaxel | 6.2 |
Number of Participants Who Discontinued Study Treatment Due To 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. An AE could therefore have been 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 study treatment due to an AE is presented. (NCT03834506)
Timeframe: Up to approximately 27 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Docetaxel | 150 |
| Placebo + Docetaxel | 115 |
Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review
ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG). (NCT03834506)
Timeframe: Up to 36.5 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab + Docetaxel | 33.5 |
| Placebo + Docetaxel | 35.3 |
"Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 (Worst Pain in 24 Hours) and Opiate Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score"
"TTPP was defined as the time from randomization to pain progression as determined by Item 3 of the BPI-SF and by the AQA score. Pain progression was defined as:~For participants asymptomatic at baseline: a ≥2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain~For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids:, a ≥2-point change from baseline in the average BPI-SF Item 3 score and an average worst pain score ≥4 and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of 2 or higher) OR any increase in opioid use at 2 consecutive follow-up visits.~TTPP was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had > 2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment." (NCT03834506)
Timeframe: Up to 36.5 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 21.1 |
| Placebo + Docetaxel | NA |
Number of Participants With a Best Overall Response of Complete Response (iCR) or Partial Response (iPR) Per iRECIST by End of Long-Term Follow-Up Period
iRECIST will be used by the Investigator to assess tumor response and progression. An iCR is defined as the disappearance of all target lesions as assessed by iRECIST; an iPR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters, as assessed by iRECIST. (NCT03837353)
Timeframe: Up to Year 2 Post-Baseline
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2) | 3 |
| Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2) | 2 |
| Cohort 1B (DKN-01 600mg [Phase II Dose], Docetaxel 75 mg/m2) | 0 |
| Cohort 2A.1 (DKN-01 300mg) | 0 |
| Cohort 2A.2 (DKN-01 600mg) | 0 |
| Cohort 2B (DKN-01 600mg [Phase 2 Dose]) | 0 |
Maximal Percent Change in PSA Measured After Treatment Initiation
(NCT03837353)
Timeframe: Up to Year 2 Post-Baseline
| Intervention | Percentage (Median) |
|---|
| Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2) | -74 |
| Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2) | -87 |
| Cohort 1B (DKN-01 600mg [Phase II Dose], Docetaxel 75 mg/m2) | 0 |
| Cohort 2A.1 (DKN-01 300mg) | 93 |
| Cohort 2A.2 (DKN-01 600mg) | 57 |
| Cohort 2B (DKN-01 600mg [Phase 2 Dose]) | 28 |
Number of Dose Limiting Toxicities Observed by End of Treatment Cycle 1
Measured among Phase I dose-escalation cohorts (arms 1A.1, 1A.2, 2A.1, and 2A.2) only. (NCT03837353)
Timeframe: Up to End of Cycle 1 (Up to Day 21 for Cohort 1A, Up to Day 28 for Cohort 2A)
| Intervention | Number of events (Mean) |
|---|
| Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2) | 0 |
| Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2) | 0 |
| Cohort 2A.1 (DKN-01 300mg) | 0 |
| Cohort 2A.2 (DKN-01 600mg) | 0 |
Progression-Free Survival (PFS)
Defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue as assessed by Investigator using iRECIST, in bone as assessed by Investigator using Prostate Cancer Working Group 3 (PCWG3), or death, whichever occurs first. (NCT03837353)
Timeframe: Up to Year 2 Post-Baseline
| Intervention | Months (Median) |
|---|
| Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2) | 6.3 |
| Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2) | 8.1 |
| Cohort 1B (DKN-01 600mg [Phase II Dose], Docetaxel 75 mg/m2) | 2 |
Number of Participants With a Decline in Prostate-Specific Antigen (PSA) of at Least 50% Relative to Baseline
(NCT03837353)
Timeframe: Up to Year 2 Post-Baseline
| Intervention | Participants (Count of Participants) |
|---|
| Cohort 1A.1 (DKN-01 300mg, Docetaxel 75 mg/m2) | 3 |
| Cohort 1A.2 (DKN-01 600mg, Docetaxel 75 mg/m2) | 2 |
| Cohort 1B (DKN-01 600mg [Phase II Dose], Docetaxel 75 mg/m2) | 0 |
| Cohort 2A.1 (DKN-01 300mg) | 0 |
| Cohort 2A.2 (DKN-01 600mg) | 0 |
| Cohort 2B (DKN-01 600mg [Phase 2 Dose]) | 0 |
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
| Intervention | months (Median) |
|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | 5.0 |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | 4.1 |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | 5.4 |
| Cohort D: Bintrafusp Alfa + Docetaxel | 2.6 |
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
| Intervention | Percentage of Participants (Number) |
|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | 45.0 |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | 66.7 |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | 44.4 |
| Cohort D: Bintrafusp Alfa + Docetaxel | 16.7 |
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
| Intervention | Participants (Count of Participants) |
|---|
| TEAEs | Serious TEAEs |
|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | 40 | 31 |
,| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | 9 | 5 |
,| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | 9 | 6 |
,| Cohort D: Bintrafusp Alfa + Docetaxel | 12 | 9 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | 1 |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | 1 |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | 0 |
| Cohort D: Bintrafusp Alfa + Docetaxel | 3 |
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)
| Intervention | months (Median) |
|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | 9.6 |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | NA |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | 10.5 |
| Cohort D: Bintrafusp Alfa + Docetaxel | 3.4 |
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
| Intervention | Participants (Count of Participants) |
|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | 9 |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | 3 |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | 2 |
| Cohort D: Bintrafusp Alfa + Docetaxel | 3 |
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
| Intervention | months (Median) |
|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | 11.4 |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | 11.8 |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | NA |
| Cohort D: Bintrafusp Alfa + Docetaxel | 16.5 |
EORTC QLQ-C30 Change in Emotional Functional Score From Baseline to Post IMRT+Nivolumab
"The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (EORTC QLQ-C30) is designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items.~Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. The emotional functional (EF) scale has 3 items (v3 items 21-24). Scores are standardized to range from 0-100. Higher scores indicate better emotional health." (NCT03894891)
Timeframe: At baseline and post IMRT+Nivolumab approximately 22 weeks from start of induction treatment.
| Intervention | units on a scale (Median) |
|---|
| Induction Docetaxel (T)+Cisplatin (P)+Nivolumab (N) Then Radioimmunotherapy (IMRT+N) Then Adjuvant N | 8.3 |
EORTC QLQ-C30 Change in Fatigue Score From Baseline to Post IMRT+Nivolumab
"The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life questionnaire (EORTC QLQ-C30) is designed to measure cancer patients' physical, psychological and social functions. The questionnaire is composed of multi-item scales and single items. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items.~Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. The fatigue scale has 3 items (v3 items 10,12,18). Scores are standardized to range from 0-100. Higher scores indicate more symptomatology." (NCT03894891)
Timeframe: At baseline and post IMRT+Nivolumab approximately 22 weeks from start of induction treatment.
| Intervention | units on a scale (Median) |
|---|
| Induction Docetaxel (T)+Cisplatin (P)+Nivolumab (N) Then Radioimmunotherapy (IMRT+N) Then Adjuvant N | 33.3 |
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with SCC of the esophagus who experienced a CR or PR for the first pembrolizumab course is presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 16.7 |
| Chemotherapy | 3.4 |
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of participants with a PD-L1 CPS ≥10 who experienced a CR or PR for the first pembrolizumab course is presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 24.0 |
| Chemotherapy | 6.9 |
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in All Participants
ORR was defined as the percentage of participants 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) as assessed using RECIST 1.1 by central imaging vendor review. The percentage of all participants who experienced a CR or PR for the first pembrolizumab course is presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Percentage of Participants (Number) |
|---|
| Pembrolizumab | 16.1 |
| Chemotherapy | 3.3 |
Number of Participants Experiencing 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. The number of participants who experienced ≥1 AE for the first pembrolizumab course are presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 62 |
| Chemotherapy | 56 |
Number of Participants Discontinuing Study Treatment Due 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. The number of participants who discontinued study treatment due to an AE for the first pembrolizumab course are presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab | 10 |
| Chemotherapy | 9 |
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (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 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 ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with a PD-L1 CPS ≥10. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 4.0 |
| Chemotherapy | 4.0 |
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
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. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 is presented for participants with SCC of the esophagus. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.3 |
| Chemotherapy | 2.8 |
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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 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 ≥1 new lesions was also considered PD. Median PFS for the first pembrolizumab course as assessed by central imaging vendor review per RECIST 1.1 in all participants is presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 2.5 |
| Chemotherapy | 2.8 |
Overall Survival (OS) in Participants With Squamous Cell Carcinoma (SCC) of the Esophagus
OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with SCC of the esophagus is presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 8.4 |
| Chemotherapy | 5.6 |
Overall Survival (OS) in Participants With Programmed Death-Ligand 1 Combined Positive Score ≥10 (PD-L1 CPS ≥10)
OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in participants with a PD-L1 CPS ≥10 is presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 12.0 |
| Chemotherapy | 5.3 |
Overall Survival (OS) in All Participants
OS was defined as the time from randomization to death due to any cause. Median OS for the first pembrolizumab course in all participants is presented. (NCT03933449)
Timeframe: From randomization through final analysis data cutoff date of 13-Feb-2019 (Up to ~24 months)
| Intervention | Months (Median) |
|---|
| Pembrolizumab | 8.4 |
| Chemotherapy | 5.6 |
Overall Survival (OS), Subgroup Analysis by Stratification Factors
Number of participants who died due to any cause. Participants last known to be alive are censored at date of last contact. (NCT03971474)
Timeframe: From date of registration to a maximum of 3 years or death
| Intervention | Participants (Number) |
|---|
| PD-L1: < 1% | PD-L1: >= 1% | Histology: Squamous | Histology: Non-squamous |
|---|
| Ramucirumab + Pembrolizumab | 21 | 19 | 18 | 27 |
,| Standard of Care (Inv. Choice) | 21 | 27 | 24 | 27 |
Investigator Assessed-progression-free Survival (IA-PFS)
"Time from date of registration to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause. Participants last known to be alive without report of progression are censored at date of last disease assessment. For participants with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan is used as the date of progression.~Symptomatic deterioration: Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. Efforts should be made to obtain objective evidence of progression after discontinuation." (NCT03971474)
Timeframe: From date of registration to a maximum of 3 years or death
| Intervention | months (Median) |
|---|
| Standard of Care (Inv. Choice) | 5.2 |
| Ramucirumab + Pembrolizumab | 4.5 |
Disease Control Rate (DCR)
"Percentage of participants with complete response (CR), partial response (PR), or stable disease as best response.~CR: Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes must have reduction in short axis to <1.0cm. All disease must be assessed using the same technique as baseline.~PR: Applies only to participants with at least one measurable lesion. At least 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline.~Stable disease: Does not qualify for CR, PR, Progression or Symptomatic Deterioration. All target measurable lesions must be assessed using the same techniques as baseline." (NCT03971474)
Timeframe: From date of registration to a maximum of 3 years or death
| Intervention | Percentage of participants (Number) |
|---|
| Standard of Care (Inv. Choice) | 73 |
| Ramucirumab + Pembrolizumab | 75 |
Investigator-Assessed Progression-Free Survival (IA-PFS), Subgroup Analysis by Stratification Factors
"Number of participants with progression assessed by local review or symptomatic deterioration, or death due to any cause. Participants last known to be alive without report of progression are censored at date of last disease assessment. For participants with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan is used as the date of progression.~Symptomatic deterioration: Global deterioration of health status requiring discontinuation of treatment without objective evidence of progression. Efforts should be made to obtain objective evidence of progression after discontinuation." (NCT03971474)
Timeframe: From date of registration to a maximum of 3 years or death
| Intervention | Participants (Number) |
|---|
| Histology: Non-squamous | Histology: Squamous | PD-L1: < 1% | PD-L1: >= 1% |
|---|
| Ramucirumab + Pembrolizumab | 34 | 23 | 27 | 24 |
,| Standard of Care (Inv. Choice) | 34 | 28 | 25 | 34 |
Response Rate (RR)
"Percentage of participants with a complete or partial, confirmed or unconfirmed response.~Complete Response (CR): Complete disappearance of all target and non-target lesions. No new lesions. No disease related symptoms. Any lymph nodes (whether target or non-target) must have reduction in short axis to < 1.0 cm. All disease must be assessed using the same technique as baseline.~Partial Response (PR): Applies only to participants with at least one measurable lesion. Greater than or equal to 30% decrease under baseline of the sum of appropriate diameters of all target measurable lesions. No unequivocal progression of non-measurable disease. No new lesions. All target measurable lesions must be assessed using the same techniques as baseline." (NCT03971474)
Timeframe: From date of registration to a maximum of 3 years or death
| Intervention | Percentage of participants (Number) |
|---|
| Standard of Care (Inv. Choice) | 28 |
| Ramucirumab + Pembrolizumab | 22 |
Overall Survival (OS)
Time 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. (NCT03971474)
Timeframe: From date of registration to a maximum of 2 years and 11 months or death
| Intervention | months (Median) |
|---|
| Standard of Care (Inv. Choice) | 11.6 |
| Ramucirumab + Pembrolizumab | 14.5 |
Duration of Response (DOR)
Time from date of first documentation of response (complete or partial) to date of first documentation of progression assessed by local review or symptomatic deterioration, or death due to any cause among participants who achieve a response. Participants last known to be alive without report of progression are censored at date of last disease assessment. For participants with a missing scan (or consecutive missing scans) whose subsequent scan determines progression, the expected date of the first missing scan (as defined by the disease assessment schedule) is used as the date of progression. (NCT03971474)
Timeframe: From date of registration to a maximum of 3 years or death
| Intervention | months (Median) |
|---|
| Standard of Care (Inv. Choice) | 5.6 |
| Ramucirumab + Pembrolizumab | 12.9 |
Serum Trough Concentration (Ctrough) of Pertuzumab During Cycle 7 (Pre-Dose Cycle 8)
The observed pertuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement. (NCT04024462)
Timeframe: Pre-dose at Cycle 8 (one cycle is 21 days)
| Intervention | micrograms per millilitre (μg/mL) (Geometric Mean) |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 69.9 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 74.6 |
Serum Ctrough of Trastuzumab During Cycle 7 (Pre-Dose Cycle 8)
The observed trastuzumab trough serum concentration (Ctrough) at Cycle 7 was assessed following 3 cycles of pertuzumab IV and trastuzumab IV or the fixed-dose combination (FDC) of pertuzumab and trastuzumab SC. The Per Protocol Pharmacokinetics (PK) analysis population includes all enrolled participants who adhered to the protocol. Exclusions from the Per Protocol PK analysis population were made for the following reasons: participants were missing the Ctrough pre-dose Cycle 8 PK sample, participants with a Ctrough sample collected with at least 2 days deviation from the planned date on Day 21 (i.e., before Day 19 or after Day 23), participants given a dose amount that deviated from the planned dose by >20% within 3 cycles (from Cycle 5), participants with a dose delay of more than 7 days, a Cycle 7 subcutaneous injection site other than thigh was used, if the Cycle 8 IV pre-dose and post-dose PK samples were switched, and an assay error impacting Ctrough measurement. (NCT04024462)
Timeframe: Pre-dose at Cycle 8 (one cycle is 21 days)
| Intervention | micrograms per milllilitre (μg/mL) (Geometric Mean) |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 33.6 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 52.1 |
Percentage of Participants With Total Pathological Complete Response (tpCR), According to Local Pathologist Assessment
Total pathological complete response (tpCR) was defined as eradication of invasive disease in the breast and axilla; that is, ypT0/is ypN0, according to the local pathologists' assessment. Pathologic response to therapy was determined at the time of surgery. The tpCR rate is the percentage of participants in the ITT population who achieved a tpCR. Participants with missing data for tpCR (i.e., do not undergo surgery or have an invalid pCR assessment) were included in the analysis and classified as non-responders. Rates of tpCR were calculated in each treatment arm and were assessed using the difference between the Arm B: Pertuzumab and Trastuzumab FDC SC and the Arm A: Pertuzumab IV and Trastuzumab IV tpCR rates and corresponding 95% Clopper-Pearson confidence intervals (CIs). The difference between the tpCR rates along with corresponding 95% Hauck-Anderson CIs were calculated. (NCT04024462)
Timeframe: Following completion of surgery (up to 33 weeks)
| Intervention | percentage of participants (Number) |
|---|
| Arm A: Pertuzumab IV + Trastuzumab IV + Chemotherapy | 56.4 |
| Arm B: Pertuzumab and Trastuzumab FDC SC + Chemotherapy | 55.6 |
Objective Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to the corresponding treatment arm [intent-to-treat (ITT) population], based on investigator-assessed tumor responses.CR is defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking in reference the baseline sum LD), no progression of non-target lesions, and no appearance of new lesions. Confirmations of CR and PR are not required. (NCT04031885)
Timeframe: Randomization to Measured Progressive Disease (Up to 12 Months)
| Intervention | percentage of participants (Number) |
|---|
| Abemaciclib + Fulvestrant | 0 |
| Standard Chemotherapy | 0 |
Pharmacokinetics (PK): Maximum Serum Concentration of Ramucirumab (Cmax)
Cmax was the concentration of study drug in the blood after the dose is administered. It was measured post-dose and was summarized using descriptive statistics. (NCT04145700)
Timeframe: 0.5 hours after the end of ramucirumab infusion on Day 1 of Cycle 1
| Intervention | microgram per milliliter (µg/mL) (Geometric Mean) |
|---|
| Ramucirumab + Gemcitabine + Docetaxel | 231 |
Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR)
ORR is the best overall tumor response of complete response (CR) or partial response (PR) as classified by the investigator according to the Response Evaluation Criteria In Solid Tumors (RECIST v1.1). CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. 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. (NCT04145700)
Timeframe: Baseline through Measured Progressive Disease (Up To 6.4 Months)
| Intervention | Percentage of participants (Number) |
|---|
| Ramucirumab + Gemcitabine + Docetaxel | 6.3 |
| Gemcitabine + Docetaxel | 0 |
Number of Participants With Treatment-Emergent Anti-Drug Antibodies (TE-ADA)
A TE-ADA evaluable participant is considered to be TE-ADA positive if the participant has at least one post baseline titer that is a 4-fold or greater increase in titer from baseline measurement (treatment-boosted). If baseline result is ADA Not Present, then the participant is TE ADA positive if there is at least one post baseline result of ADA Present with titer >= 20 (treatment-induced). (NCT04145700)
Timeframe: Baseline Up to 6.94 months
| Intervention | Participants (Count of Participants) |
|---|
| Ramucirumab + Gemcitabine + Docetaxel | 0 |
| Gemcitabine + Docetaxel | 0 |
Duration of Response (DoR)
DoR is defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective disease progression is observed, per RECIST 1.1 criteria, or the date of death from any cause in the absence of documented disease progression or recurrence. (NCT04145700)
Timeframe: Date of CR or PR to Date of Objective Disease Progression or Death Due to Any Cause (Up To 4.13 Months)
| Intervention | Months (Number) |
|---|
| Ramucirumab + Gemcitabine + Docetaxel | NA |
Complete Response (CR): Percentage of Participants Who Achieve CR
CR is a disappearance of all target and non-target lesions and normalization of tumor marker level. (NCT04145700)
Timeframe: Baseline Up to 6.94 months
| Intervention | Percentage of participants (Number) |
|---|
| Ramucirumab + Gemcitabine + Docetaxel | 0 |
| Gemcitabine + Docetaxel | 0 |
Progression Free Survival (PFS)
PFS is defined as the time from randomization until the first investigator-determined objective progression as defined by Response Evaluation Criteria In Solid Tumors, Version 1.1 (RECIST v1.1) or death from any cause in the absence of progressive disease. Participants known to be alive and without disease progression will be censored at the time of the last adequate tumor assessment or date of randomization, whichever is later. (NCT04145700)
Timeframe: Baseline to Objective Progression or Death Due to Any Cause (Up To 6.4 Months)
| Intervention | Months (Median) |
|---|
| Ramucirumab + Gemcitabine + Docetaxel | 2.10 |
| Gemcitabine + Docetaxel | 2.03 |
PK: Minimum Serum Concentration of Ramucirumab (Cmin)
Cmin was the concentration of study drug in the blood immediately before the next dose was administered. It was measured pre-dose at all visits and was summarized using descriptive statistics. (NCT04145700)
Timeframe: Prior to ramucirumab infusion on Day 8 of Cycle 1, Day 1 of Cycle 2 and Day 1 of Cycle 5
| Intervention | microgram per milliliter (µg/mL) (Geometric Mean) |
|---|
| Day 8 of Cycle 1 | Day 1 of Cycle 2 | Day 1 of Cycle 5 |
|---|
| Ramucirumab + Gemcitabine + Docetaxel | 73.3 | 55.4 | NA |
Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)
DLT is defined as an event that is clinically significant and not clearly related to disease progression or intercurrent illness that occurred within the DLT observation period of the Cycle 1 timeframe. (NCT04165031)
Timeframe: Cycle 1 (21 Day Cycle)
| Intervention | Participants (Count of Participants) |
|---|
| LY3499446 Phase 1 Cohort A1 (High Dose) | 2 |
| LY3499446 Phase 1 Cohort AO (Mid Dose) | 1 |
| LY3499446 Phase 1 Cohort A-2 (Low Dose) | 1 |
Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446
Average concentration after the first dose of LY3499446. (NCT04165031)
Timeframe: Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose
| Intervention | nanograms per milliliter (ng/mL) (Geometric Mean) |
|---|
| LY3499446 Phase 1 Cohort A1 (High Dose) | NA |
| LY3499446 Phase 1 Cohort AO (Mid Dose) | NA |
| LY3499446 Phase 1 Cohort A-2 (Low Dose) | NA |
Progression-free Survival (PFS)
"PFS was defined as the time from randomization (baseline) until disease progression or death from any cause, whichever occurred first for all participants. Progression was based on blinded independent central review (BICR) of disease response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).~As pre-specified in the statistical analysis plan, for participants who crossed over from docetaxel to AMG 510, the participant's response post first progression or post crossover was not used for the primary analyses. Data are presented per original treatment randomized." (NCT04303780)
Timeframe: Baseline up to primary analysis data cut-off date (02 August 2022); max time on study as of primary analysis data cut off was 24.3 months
| Intervention | months (Median) |
|---|
| AMG 510 | 5.62 |
| Docetaxel | 4.47 |
3-Month Complete Response Rate
Number of patients with no evidence of recurrent high grade urothelial carcinoma of the bladder of any stage as assessed by cystoscopy with biopsy and urine cytology. (NCT04386746)
Timeframe: 3 months
| Intervention | Participants (Count of Participants) |
|---|
| Intravesical Gemcitabine/Docetaxel | 25 |
Time to Confirmed Deterioration in Patient-Reported Global Health Status (GHS)
"Time to confirmed deterioration (TTCD) analyses was performed for global health status (GHS) and quality of life (QoL) (items 29 and 30) of EORTC QLQ-C30. GHS/ QoL items are scored on a 7-point scale that ranges from very poor to excellent. TTCD for GHS/QoL is defined as the time from the date of randomization to the first confirmed clinically meaningful decrease from baseline in GHS/QoLscore held for at least two consecutive assessments or an initial clinically meaningful decrease from baseline followed by death from any cause within 21 days or until the next tumor assessment, whichever occurs first. A score change of >=10-point on the EORTC QLQ-C30 GHS/QoL scale was determined as being clinically meaningful. Scores were averaged, transformed to 0-100 scale; where higher score for GHS/QoL=better health-related QoL. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley." (NCT04471428)
Timeframe: Up to approximately 24 months
| Intervention | months (Median) |
|---|
| Docetaxel | 14.1 |
| Atezolizumab + Cabozantinib | 8.1 |
Minimum Plasma Concentration (Cmin) of Cabozantinib
(NCT04471428)
Timeframe: Predose on Day 1 of Cycles 1, 2, 3, 4, and 5 (each cycle is 21 days)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 | Cycle 3 Day 1 | Cycle 4 Day 1 | Cycle 5 Day 1 |
|---|
| Atezolizumab + Cabozantinib | NA | 0.746 | 0.418 | 0.469 | 0.303 |
Confirmed Objective Response Rate (ORR) as Determined by Investigator
Confirmed ORR was defined as the percentage of participants with a complete response (CR) or partial response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1. CR: disappearance of all target lesions. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters. (NCT04471428)
Timeframe: Up to approximately 24 months
| Intervention | percentage of participants (Number) |
|---|
| Docetaxel | 13.3 |
| Atezolizumab + Cabozantinib | 11.8 |
Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
(NCT04471428)
Timeframe: Predose on Day 1 of Cycles 1,2,3,4,8,12 and 16 (each cycle is 21 days) and at post-treatment follow-up visit (≤ 30 days after final dose)
| Intervention | Participants (Count of Participants) |
|---|
| ADA Prevalence at Baseline | ADA Incidence after treatment |
|---|
| Atezolizumab + Cabozantinib | 2 | 37 |
OS Rates
Overall Survival (OS) rate is defined as the percentage of participants who were alive at 1 year and 2 years. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. (NCT04471428)
Timeframe: 1 and 2 years
| Intervention | percentage of participants (Number) |
|---|
| 1 year | 2 years |
|---|
| Atezolizumab + Cabozantinib | 43.27 | NA |
,| Docetaxel | 44.12 | NA |
PFS Rates Assessed by Investigator
PFS rates were defined as the percentage of participants alive and without progression as assessed by the investigator according to RECIST v1.1. Progressive disease (PD) was defined as 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 of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. (NCT04471428)
Timeframe: 6 months and 1 year
| Intervention | percentage of participants (Number) |
|---|
| 6 months | 1 year |
|---|
| Atezolizumab + Cabozantinib | 39.51 | 14.70 |
,| Docetaxel | 23.66 | 8.38 |
Overall Survival (OS)
OS was defined as the time from randomization to death from any cause. Participants alive at the time of the analysis were censored at the date when they were last known to be alive as documented by the investigator. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley. (NCT04471428)
Timeframe: Up to approximately 24 months
| Intervention | months (Median) |
|---|
| Docetaxel | 10.5 |
| Atezolizumab + Cabozantinib | 10.7 |
Maximum Serum Concentration (Cmax) of Atezolizumab
(NCT04471428)
Timeframe: Postdose on Day 1 of Cycle 1 (each cycle is 21 days)
| Intervention | μg/mL (Geometric Mean) |
|---|
| Atezolizumab + Cabozantinib | 450 |
Progression-Free Survival (PFS) as Determined by Investigator
PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause (whichever occurred first). Progressive disease (PD) was defined as 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 of the target lesions recorded since the treatment started, including screening, or the appearance of one or more new lesions. Participants who were alive and did not experience disease progression at the time of analysis, were censored on the date of last tumor assessment. Participants with no post-baseline tumor assessment were censored at the date of randomization. (NCT04471428)
Timeframe: Up to approximately 24 months
| Intervention | months (Median) |
|---|
| Docetaxel | 4.0 |
| Atezolizumab + Cabozantinib | 4.6 |
Duration of Response (DOR) as Determined by Investigator
DOR for participants with confirmed ORR was defined as time from first occurrence of documented objective response to disease progression (PD), as determined by investigator according to RECIST v1.1, or death from any cause (whichever occurred first). PD was defined as at least 20% increase in sum of longest diameters of target lesions, taking as reference the smallest sum of longest diameters of target lesions recorded since treatment started, including screening, or appearance of one or more new lesions. Confirmed ORR was defined as percentage of participants with a CR or PR on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1. Participants who had not progressed and who did not die at the time of analysis were censored at the time of last tumor assessment date. Kaplan-Meier method was used to estimate median. 95% CI for median was computed using method of Brookmeyer and Crowley. (NCT04471428)
Timeframe: Up to approximately 24 months
| Intervention | months (Median) |
|---|
| Docetaxel | 4.30 |
| Atezolizumab + Cabozantinib | 5.55 |
Time to Confirmed Deterioration in Patient-Reported Physical Functioning (PF)
Time to confirmed deterioration (TTCD) analyses was performed for patient-reported physical functioning (PF) (items 1 to 5) of European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 Questionnaire (EORTC QLQ-C30). The PF is measured on 4-point scale (1='Not at all' to 4='Very much'). TTCD for PF is defined as time from date of randomization to first confirmed clinically meaningful decrease from baseline in PF score held for at least 2 consecutive assessments or initial clinically meaningful decrease from baseline followed by death from any cause within 21 days or until next tumor assessment, whichever occurs first. A score change of >=of 10-point on EORTC QLQ-C30 PF scale was determined as being clinically meaningful. Scores were averaged, transformed to 0-100 scale; where higher score represented high/healthy level of functioning. Kaplan-Meier method was used to estimate the median. 95% CI for median was computed using the method of Brookmeyer and Crowley (NCT04471428)
Timeframe: Up to approximately 24 months
| Intervention | months (Median) |
|---|
| Docetaxel | 5.6 |
| Atezolizumab + Cabozantinib | 7.7 |
Minimum Serum Concentration (Cmin) of Atezolizumab
(NCT04471428)
Timeframe: Predose on Day 1 of Cycles 2, 3, 4, 8, 12 and 16 (each cycle is 21 days)
| Intervention | microgram/milliliter (μg/ml) (Geometric Mean) |
|---|
| Cycle 1 Day 1 | Cycle 2 Day 1 | Cycle 3 Day 1 | Cycle 4 Day 1 | Cycle 8 Day 1 | Cycle 12 Day 1 | Cycle 16 Day 1 |
|---|
| Atezolizumab + Cabozantinib | NA | 96.8 | 124 | 167 | 194 | 233 | 209 |
Incidence of Treatment-Emergent Adverse Events as Assessed by CTCAE v5.0
To assess the effects of trilaciclib administered prior to docetaxel compared with placebo administered prior to docetaxel on occurrence and severity of adverse events (AEs) by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5, study treatment discontinuation due to adverse events (AEs), and trilaciclib adverse events of special interest (AESI) in patients with metastatic NSCLC receiving docetaxel in the second or third line. (NCT04863248)
Timeframe: Time from date of first dose of trilaciclib/placebo and docetaxel through 30 days following the last dose of trilaciclib/placebo and docetaxel, assessed up to 9 months and 2 days.
| Intervention | participants (Number) |
|---|
| Any AE | Any AE of Grade >= 3 | Any AE of Grade >= 4 |
|---|
| Placebo + Docetaxel | 3 | 3 | 3 |
,| Trilaciclib + Docetaxel | 4 | 2 | 0 |
Time to Radiographic Soft Tissue Progression Per Soft Tissue Rules of Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
The time to radiographic soft tissue progression was defined as the time from randomization to radiographic soft tissue progression per soft tissue rules of PCWG-modified RECIST 1.1 as assessed by BICR. Progression 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 progression. Time to radiographic soft tissue progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without radiographic soft tissue progression were censored at the last evaluable assessment. The time to radiographic soft tissue progression results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | NA |
| Placebo + Docetaxel | 11.2 |
Time to Prostate-specific Antigen (PSA) Progression
The time to PSA progression was the time from randomization to PSA progression. The PSA progression date was defined as the date of: 1. ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR 2. ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no PSA decline from baseline Time to PSA progression was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without PSA progression were censored at the last evaluable assessment. The time to PSA progression results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 5.0 |
| Placebo + Docetaxel | 3.7 |
Time to Initiation of the First Subsequent Anti-cancer Therapy (TFST)
TFST was defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death; whichever occurred first. The TFST was calculated using the product-limit (Kaplan-Meier) method for censored data. Any participant not known to have further subsequent therapy or death was censored at the last known time that no subsequent new anti-cancer therapy was received. The TFST results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 9.4 |
| Placebo + Docetaxel | 8.3 |
Radiographic Progression-free Survival (rPFS) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
rPFS was defined as the time from randomization to occurrence of: radiological tumor progression using RECIST 1.1 as assessed by BICR; progression of bone lesions using PCWG criteria; or death due to any cause. Progression as per RECIST 1.1 was ≥20% increase in sum of diameters of target lesions and progression of existing non-target lesions. Progression of bone lesions by PCWG criteria was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and was persistent for ≥6 weeks. The rPFS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without a rPFS event were censored at the date of last disease assessment. The rPFS results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 6.4 |
| Placebo + Docetaxel | 11.2 |
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the analysis were censored at the date of the last follow-up. The OS results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | 16.3 |
| Placebo + Docetaxel | 13.9 |
Objective Response Rate (ORR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review
ORR was defined as the percentage of participants with complete response (CR: disappearance of all target lesions per RECIST 1.1; and no evidence of disease (NED) on bone scan per PCWG) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions per RECIST 1.1; and non-progressive disease, non-evaluable [NE], or NED on bone scan or CR with non-progressive disease or NE bone scan per PCWG). The ORR results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab + Docetaxel | 17.6 |
| Placebo + Docetaxel | 13.3 |
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. An AE could therefore have been 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 experienced an AE is presented. (NCT04907227)
Timeframe: Up to 17 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Docetaxel | 37 |
| Placebo + Docetaxel | 34 |
Prostate-specific Antigen (PSA) Response Rate
The Prostate-specific Antigen (PSA) response rate was the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response. The analysis was performed on participants who had baseline PSA measurements. The PSA response rate results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Percentage of participants (Number) |
|---|
| Pembrolizumab + Docetaxel | 24.4 |
| Placebo + Docetaxel | 22.5 |
Duration of Response (DOR) Per Prostate Cancer Working Group (PCWG)-Modified Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review
DOR was defined as the time from first documented evidence of complete response (CR) or partial response (PR) per PCWG and RECIST 1.1 criteria until progressive disease (PD) or death. PD per RECIST 1.1 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. PD per PCWG was the appearance of ≥2 new bone lesions on bone scan, that have been confirmed to not represent tumor flare, and were persistent for ≥6 weeks. The DOR was calculated using the product-limit (Kaplan-Meier) method for censored data. If a participant had not progressed, the participant was censored at the date of last disease assessment. The DOR results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | NA |
| Placebo + Docetaxel | NA |
Number of Participants Who Discontinued Study Treatment Due To 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. An AE could therefore have been 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 study treatment due to an AE is presented. (NCT04907227)
Timeframe: Up to 14 months
| Intervention | Participants (Count of Participants) |
|---|
| Pembrolizumab + Docetaxel | 3 |
| Placebo + Docetaxel | 6 |
"Time to Pain Progression (TTPP) as Assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 (Worst Pain in 24 Hours) and Opiate Analgesic Use Assessed by the Analgesic Quantification Algorithm [AQA] Score"
TTPP=the time from randomization to pain progression determined by BPI-SF Item 3 and the AQA score. Pain progression was defined as: 1. For participants asymptomatic at baseline: a ≥2-point change from baseline in the average (4-7 days) BPI-SF item 3 score at 2 consecutive visits OR initiation of opioid use for pain 2. For participants symptomatic at baseline (average BPI-SF Item 3 score >0 and/or currently taking opioids:, a ≥2-point change from baseline in the average BPI-SF Item 3 score and an average worst pain score ≥4 and no decrease in average opioid use (≥1-point decrease in AQA score from a starting value of ≥2) OR any increase in opioid use at 2 consecutive follow-up visits. TTPP was calculated using the product-limit (Kaplan-Meier) method for censored data. Participants who had >2 consecutive visits that were not evaluable for pain progression were censored at the last evaluable assessment. The TTPP results are based on data from the primary completion data cut-off date. (NCT04907227)
Timeframe: Up to 19.8 months
| Intervention | Months (Median) |
|---|
| Pembrolizumab + Docetaxel | NA |
| Placebo + Docetaxel | NA |
Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline
Blood samples were collected for assessment of the clinical chemistry parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with clinical chemistry results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Blood bilirubin increased | Hypercalcemia | Creatinine increased |
|---|
| Docetaxel 75 mg/m^2 | 0 | 0 | 0 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 1 | 2 | 1 |
Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline
Blood samples were collected for assessment of the hematology parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with Hematology results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Anemia | Leukocytosis | White blood cell decreased | Lymphocyte count decreased | Neutrophil count decreased | Platelet count decreased |
|---|
| Docetaxel 75 mg/m^2 | 2 | 0 | 5 | 4 | 4 | 0 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 5 | 1 | 11 | 12 | 13 | 3 |
Objective Response Rate
ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel 75 mg/m^2 | 11 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m2 | 19 |
Kaplan-Meier Estimates of iRECIST Progression-free Survival (iPFS)
iPFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 3.3 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m2 | 3.4 |
Minimum Observed Concentration (CmIn) of Feladilimab
Blood samples were collected for assessment of the pharmacokinetic parameters. (NCT05553808)
Timeframe: Week 1
| Intervention | nanogram per millimeter (ng/mL) (Geometric Mean) |
|---|
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 6104.6 |
Overall Survival
Overall survival was calculated as time from randomization to death. Confidence Intervals estimated using the Brookmeyer Crowley method. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 8.2 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 7.8 |
Kaplan-Meier Estimates of Progression-Free Survival (PFS)
PFS is defined as time from the date of randomization to the date of disease progression as per RECIST v1.1. or death whichever occurs earlier. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 3.3 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m2 | 3.4 |
Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline
Blood Pressure was measured after 5 minutes of rest and was taken in the same position throughout the study. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE. Number of participants with vital signs results by maximum grade increase (Increase to Grade 2 or Increase to Grade 3) are presented. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Diastolic Blood Pressure | Systolic Blood Pressure |
|---|
| Docetaxel 75 mg/m^2 | 12 | 16 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 26 | 28 |
Disease Control Rate (DCR)
DCR is defined as the percentage of participants with a confirmed CR + PR at any time, plus SD =>12 weeks as per RECIST v1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel 75 mg/m^2 | 40 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 50 |
iRECIST Objective Response Rate (iORR)
iORR is defined as the percentage of participants with a confirmed iCR or iPR at any time per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Percentage of Participants (Number) |
|---|
| Docetaxel 75 mg/m^2 | 11 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 19 |
Kaplan-Meier Estimates of Duration of Response (DOR) in Participants With Objective Response
DOR is defined as the time for first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 4.8 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 4.3 |
Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable
CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Complete Response | Partial Response | Stable Disease | Progressive Disease | Not Evaluable |
|---|
| Docetaxel 75 mg/m^2 | 0 | 4 | 10 | 14 | 7 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 0 | 13 | 22 | 23 | 12 |
Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable
Modified RECIST 1.1 for immune-based therapeutics (iRECIST) is based on RECIST v 1.1 but adapted to account for the unique tumor response seen with immunotherapeutic drugs. iRECIST was used to assess tumor response and progression and make treatment decisions. iCR: disappearance of all target lesions; iPR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). iCPD: either 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; iSD: stable disease in the absence of CR or PD and iUPD: unconfirmed progressive disease when PD is unconfirmed and NE: not evaluable. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| iCR | iPR | iUPD | iCPD | iSD | Not Evaluable |
|---|
| Docetaxel 75 mg/m^2 | 0 | 4 | 11 | 3 | 10 | 7 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 0 | 13 | 15 | 8 | 22 | 12 |
Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline
Pulse Rate was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to <50 beats per minute, Change to Normal or No Change and Increase to >120 beats per minute. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Decrease to <50 beats per minute | Change to Normal or No Change | Increase to >120 beats per minute |
|---|
| Docetaxel 75 mg/m^2 | 0 | 32 | 2 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 0 | 55 | 8 |
Kaplan-Meier Estimates of iRECIST Duration of Response (iDOR) in Participants With Objective Response
iDOR is defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Months (Median) |
|---|
| Docetaxel 75 mg/m^2 | 4.8 |
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 4.3 |
Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline
Body temperature was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to <=35 Degrees Celsius, Change to Normal or No Change and Increase to >=38 Degrees Celsius. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| Decrease to <=35 Degrees Celsius | Change to Normal or No Change | Increase to >=38 Degrees Celsius |
|---|
| Docetaxel 75 mg/m^2 | 0 | 33 | 1 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 6 | 52 | 5 |
Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months
Overall survival was defined as the time between date of randomization and death due to any cause. Kaplan-Meier estimates of the percentage of participants who died at each time point was calculated. Confidence Intervals estimated using the Brookmeyer Crowley method. (NCT05553808)
Timeframe: Month 12 and 18
| Intervention | Percentage of Participants (Number) |
|---|
| Month 12 | Month 18 |
|---|
| Docetaxel 75 mg/m^2 | 44 | 28 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 28 | 18 |
Maximum Observed Concentration (Cmax) of Docetaxel
Blood samples were collected for assessment of the pharmacokinetic parameters. (NCT05553808)
Timeframe: Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19 and Week 22
| Intervention | nanogram per millimeter (ng/mL) (Geometric Mean) |
|---|
| Week 1 | Week 4 | Week 7 | Week 10 | Week 13 | Week 16 | Week 19 | Week 22 |
|---|
| Docetaxel 75 mg/m^2 | 1500.9 | 1587.1 | 846.8 | 1262.9 | 1354.2 | 1095.3 | 759.0 | 535.5 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 1429.9 | 1399.7 | 1036.9 | 1248.4 | 1363.4 | 1381.9 | 1765.7 | 2430.7 |
Maximum Observed Concentration (Cmax) of Feladilimab
Blood samples were collected for assessment of the pharmacokinetic parameters. (NCT05553808)
Timeframe: Week 1, Week 13 and Week 25
| Intervention | nanogram per millimeter (ng/mL) (Geometric Mean) |
|---|
| Week 1 | Week 13 | Week 25 |
|---|
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 24923.7 | 28715.9 | 32688.4 |
Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. AESI are considered to be Infusion Related Reactions (IRRs) and those of potential immunologic etiology. (NCT05553808)
Timeframe: Up to 2 years
| Intervention | Participants (Count of Participants) |
|---|
| AEs | AESI | SAEs | AEs leading to permanent discontinuation of study treatment | AEs leading to dose reduction | AEs leading to dose interruption/delay |
|---|
| Docetaxel 75 mg/m^2 | 34 | 1 | 16 | 12 | 7 | 11 |
,| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 70 | 4 | 34 | 16 | 13 | 24 |
Number of Participants With Positive ADA Against Feladilimab
(NCT05553808)
Timeframe: Week 1, 4, 7, 10, 13, 16, 19, 22, 25, 37, 49, 61 and 73
| Intervention | Participants (Count of Participants) |
|---|
| Week 1 | Week 4 | Week 7 | Week 10 | Week 13 | Week 16 | Week 19 | Week 22 | Week 25 | Week 37 | Week 49 | Week 61 | Week 73 |
|---|
| Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 | 1 | 8 | 4 | 2 | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 |