niacinamide and Pancreatic Neoplasms studies

nicotinamide : A pyridinecarboxamide that is pyridine in which the hydrogen at position 3 is replaced by a carboxamide group.

Pancreatic Neoplasms: Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).

Research Excerpts

Excerpt	Relevance	Reference
"Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i."	9.19	A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study. ( Aparicio, J; Ayuso, JR; Conill, C; Feliu, J; Fuster, D; García-Mora, C; Martín, M; Maurel, J; Petriz, ML; Sánchez-Santos, ME, 2014)
"Preclinical trials of a mouse model of pancreatic neuroendocrine tumors (PNET) were conducted to determine whether dual FGF/VEGF pathway inhibition with brivanib can improve first-line efficacy in comparison with VEGF inhibitors lacking fibroblast growth factor (FGF)-inhibitory activity and to characterize second-line brivanib activity before and after the onset of evasive resistance to VEGF-selective therapy."	7.77	Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. ( Allen, E; Hanahan, D; Walters, IB, 2011)
"All patients had pancreatic or biliary tract cancer."	6.78	A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study. ( Deming, DA; Goggins, T; Groteluschen, D; Hernan, HR; Holen, KD; LoConte, NK; Lubner, SJ; Mulkerin, DL; Oettel, K; Robinson, E; Schelman, WR; Traynor, AM, 2013)
"We performed a multicenter phase II study of sorafenib 200 mg orally twice daily along with oxaliplatin 85 mg/m(2) IV on days 1 and 15, followed by capecitabine 2250 mg/m(2) orally every 8 h for six doses starting on days 1 and 15 of a 28-day cycle in patients who had no more than one previous chemotherapy regimen for their pancreatic adenocarcinoma."	5.20	A phase II study of sorafenib, oxaliplatin, and 2 days of high-dose capecitabine in advanced pancreas cancer. ( Eickhoff, J; Groteluschen, D; LoConte, NK; Lubner, SJ; Makielski, RJ; Mulkerin, DL; Traynor, AM, 2015)
"Locally advanced or metastatic pancreatic adenocarcinoma patients were randomized in a 1:1 ratio to receive cisplatin plus gemcitabine with sorafenib 400mg bid (arm A) or without sorafenib (arm B)."	5.19	Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study. ( Aitini, E; Barni, S; Berardi, R; Bidoli, P; Boni, C; Caprioni, F; Cascinu, S; Cinquini, M; Conte, P; Di Costanzo, F; Faloppi, L; Ferrari, D; Labianca, R; Mosconi, S; Siena, S; Sobrero, A; Tonini, G; Villa, F; Zagonel, V, 2014)
"Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i."	5.19	A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study. ( Aparicio, J; Ayuso, JR; Conill, C; Feliu, J; Fuster, D; García-Mora, C; Martín, M; Maurel, J; Petriz, ML; Sánchez-Santos, ME, 2014)
" In endocrine tumors, several molecules have demonstrated efficacy in terms of progression free survival during phase III trials such as vandetanib and cabozantinib in medullary thyroid carcinoma, sorafenib in differentiated thyroid carcinoma and everolimus or sunitinib for pancreatic neuroendocrine tumors."	4.89	[Targeted therapies, prognostic and predictive factors in endocrine oncology]. ( Baudin, E; Borson-Chazot, F; Hescot, S; Lombès, M, 2013)
"Single and multiple oral doses of everolimus and sorafenib were administered alone and in combination in immunocompetent male mice and to severe combined immune-deficient (SCID) mice bearing low-passage, patient-derived pancreatic adenocarcinoma in seven different studies."	3.79	Physiologically based pharmacokinetic models for everolimus and sorafenib in mice. ( Fetterly, GJ; Hylander, BH; Jusko, WJ; Ma, WW; Pawaskar, DK; Repasky, EA; Straubinger, RM, 2013)
"Preclinical trials of a mouse model of pancreatic neuroendocrine tumors (PNET) were conducted to determine whether dual FGF/VEGF pathway inhibition with brivanib can improve first-line efficacy in comparison with VEGF inhibitors lacking fibroblast growth factor (FGF)-inhibitory activity and to characterize second-line brivanib activity before and after the onset of evasive resistance to VEGF-selective therapy."	3.77	Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition. ( Allen, E; Hanahan, D; Walters, IB, 2011)
"Patients with refractory solid tumors were enrolled utilizing a 3+3 dose-escalation design."	3.30	A phase I trial of riluzole and sorafenib in patients with advanced solid tumors: CTEP #8850. ( Aisner, J; Cerchio, R; Chan, N; Chen, S; Ganesan, S; Goodin, S; Gounder, M; Li, J; Lin, H; Malhotra, J; Marinaro, C; Mehnert, JM; Portal, DE; Shih, W; Silk, AW; Spencer, KR; Stein, MN, 2023)
"We assessed the role of LDH in advanced pancreatic cancer receiving sorafenib."	2.80	The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib. ( Aitini, E; Andrikou, K; Barni, S; Berardi, R; Bianconi, M; Bittoni, A; Boni, C; Caprioni, F; Cascinu, S; Cinquini, M; Faloppi, L; Fanello, S; Ferrari, D; Giampieri, R; Labianca, R; Mosconi, S; Scartozzi, M; Sobrero, A; Torri, V; Zaniboni, A, 2015)
" Sorafenib was dosed orally 400 mg twice daily until progression, except during CRT when it was escalated from 200 mg to 400 mg daily, and 400 mg twice daily."	2.79	Phase 1 pharmacogenetic and pharmacodynamic study of sorafenib with concurrent radiation therapy and gemcitabine in locally advanced unresectable pancreatic cancer. ( Akisik, FM; Anderson, S; Bu, G; Cardenes, HR; Chiorean, EG; Clark, R; Deluca, J; DeWitt, J; Helft, P; Johnson, CS; Johnston, EL; Loehrer, PJ; Perkins, SM; Sandrasegaran, K; Schneider, BP; Shahda, S; Spittler, AJ, 2014)
"All patients had pancreatic or biliary tract cancer."	2.78	A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study. ( Deming, DA; Goggins, T; Groteluschen, D; Hernan, HR; Holen, KD; LoConte, NK; Lubner, SJ; Mulkerin, DL; Oettel, K; Robinson, E; Schelman, WR; Traynor, AM, 2013)
"Patients with metastatic pancreatic cancer were randomized to sorafenib alone (arm A) or sorafenib with gemcitabine (arm B)."	2.77	A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer. ( El-Khoueiry, AB; Gandara, D; Lenz, HJ; Ramanathan, RK; Shibata, S; Wright, JJ; Yang, DY; Zhang, W, 2012)
"Sorafenib is an oral anticancer agent targeting Ras-dependent signaling and angiogenic pathways."	2.77	BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. ( Dahan, L; Delpero, JR; Esterni, B; François, E; Gasmi, M; Genre, D; Gilabert, M; Giovannini, M; Gonçalves, A; Lamy, R; Largillier, R; Moureau-Zabotto, L; Perrier, H; Raoul, JL; Re, D; Seitz, JF; Tchiknavorian, X; Turrini, O; Viens, P, 2012)
"The response of pancreatic cancer to treatments remains unsatisfactory, highlighting the need for more effective therapeutic regimens."	2.46	In vitro and in vivo antitumor efficacy of docetaxel and sorafenib combination in human pancreatic cancer cells. ( Amadori, D; Arienti, C; Carloni, S; Chiadini, E; Fabbri, F; Leonetti, C; Milandri, C; Orlandi, A; Passeri, D; Scarsella, M; Silvestrini, R; Tesei, A; Ulivi, P; Zoli, W; Zupi, G, 2010)
"In advanced pancreatic cancer, single-agent gemcitabine became the standard therapy approximately 10 years ago."	2.44	New therapeutic directions for advanced pancreatic cancer: targeting the epidermal growth factor and vascular endothelial growth factor pathways. ( Burris, H; Rocha-Lima, C, 2008)
" High-dose nicotinamide should still, however, be considered as a drug with toxic potential at adult doses in excess of 3 gm/day and unsupervised use should be discouraged."	2.41	Safety of high-dose nicotinamide: a review. ( Bingley, PJ; Douek, IF; Gale, EA; Gillmor, HA; Knip, M; McLean, AE; Moore, WP, 2000)
"In previously established pancreatic cancer xenografts in mice, β- lapachone inhibited the tumor growth when given orally rather than when combined with cyclodextrin to improve its bioavailability."	1.72	β-lapachone: A Promising Anticancer Agent with a Unique NQO1 Specific Apoptosis in Pancreatic Cancer. ( Iqbal, MS; Khan, R; Qadir, MI, 2022)
"Furthermore, hyperglycemia is one of the severe ADRs from antineoplastics, which must be paid special attention to when treating in pancreatic carcinoma, especially doxorubicin, fluorouracil, and gemcitabine."	1.46	Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. ( He, J; Jia, B; Yan, J; Yang, J, 2017)
" Pharmacokinetic analysis revealed that oral dosing of t-CUPM resulted in higher blood levels than that of sorafenib throughout the complete time course (48 h)."	1.43	Inhibition of mutant KrasG12D-initiated murine pancreatic carcinoma growth by a dual c-Raf and soluble epoxide hydrolase inhibitor t-CUPM. ( Hammock, BD; Hwang, SH; Li, H; Liao, J; Liu, JY; Wecksler, AT; Yang, GY; Yang, J; Yang, Y, 2016)
"The effect of ZLJ33 on pancreatic cancer was mainly mediated by inactivation of p-PDGFRβ, p-c-Raf, and p-RET."	1.42	The molecular mechanisms of a novel multi-kinase inhibitor ZLJ33 in suppressing pancreatic cancer growth. ( Chen, X; Feng, Z; Li, C; Li, Y; Niu, F; Tang, K; Yang, H; Zhang, L; Zhou, W, 2015)
" Together our findings indicate that valproate which act as inhibitor of cell proliferation and inducer of apoptosis in human cancer MIAPaca2 cells when used in combination with nicotinamide makes it a potentially good candidate for new anticancer drug development."	1.40	Synergistic anticancer activity of valproate combined with nicotinamide enhances anti-proliferation response and apoptosis in MIAPaca2 cells. ( Ahmadian, S; Jafary, H; Soleimani, M, 2014)
"Sorafenib is a multikinase inhibitor of the Ras/Raf/MEK/ERK pathway and of tumor angiogenesis."	1.39	Enhancing sorafenib-mediated sensitization to gemcitabine in experimental pancreatic cancer through EMAP II. ( Awasthi, N; Hinz, S; Schwarz, MA; Schwarz, RE; Zhang, C, 2013)
"The in vitro data for two pancreatic cancer cell lines suggest that a combination of these two drugs would be no more efficacious than the individual drugs alone, consistent with the drug interaction analysis that indicated slight antagonism for growth inhibition."	1.39	Interactions of everolimus and sorafenib in pancreatic cancer cells. ( Fetterly, GJ; Jusko, WJ; Ma, WW; Pawaskar, DK; Straubinger, RM, 2013)
"Treatment with sorafenib resulted in more than 7 months of progression-free survival."	1.38	A rare case of metastatic pancreatic hepatoid carcinoma treated with sorafenib. ( Barbara, C; Barni, S; Cabiddu, M; Colombo, S; Corti, D; Elia, S; Ghilardi, M; Petrelli, F; Stringhi, E, 2012)
"Both the metastasis and the primary thyroid tumor are positive for BRAF(V600E) mutation."	1.38	Pancreatic metastasis arising from a BRAF(V600E)-positive papillary thyroid cancer: the role of endoscopic ultrasound-guided biopsy and response to sorafenib therapy. ( Abalkhail, H; Al Sohaibani, F; Almanea, H; AlQaraawi, A; Alzahrani, AS, 2012)
"Sorafenib is considered to be a potent inhibitor of tumor angiogenesis and neovascularization in various solid tumors."	1.38	Sorafenib inhibits tumor growth and improves survival in a transgenic mouse model of pancreatic islet cell tumors. ( Bartsch, DK; Buchholz, M; Fendrich, V; Holler, JP; Maschuw, K; Rehm, J; Slater, EP; Waldmann, J, 2012)
"Long-term stabilization of advanced renal cell carcinoma (RCC) by the sequence of sorafenib monotherapy followed by sunitinib and everolimus treatments in a man with multiple metastases is reported."	1.37	Long-term stable disease in metastatic renal cell carcinoma: sorafenib sequenced to sunitinib and everolimus: a case study. ( Beck, J; Bellmunt, J; Escudier, B, 2011)
"Sorafenib was continued despite two episodes of grade 3 skin toxicity; it delayed tumor progression compared to the previous immunotherapy and chemotherapy."	1.37	Pancreatic endocrine tumors: a report on a patient treated with sorafenib. ( Hong, SH; Jeon, EK; Jeong, HK; Ko, YH; Lee, SL; Roh, SY; Shin, OR; Won, HS, 2011)
"Human pancreatic cancer cell lines (PANC-1 and BxPC-3) were preincubated with sorafenib (Nexavar) alone or followed by TRAIL."	1.36	Sorafenib inhibits STAT3 activation to enhance TRAIL-mediated apoptosis in human pancreatic cancer cells. ( Huang, S; Sinicrope, FA, 2010)
"Recent evidence suggests that pancreatic cancer and other solid tumors contain a subset of tumorigenic cells capable of extensive self-renewal that contribute to metastasis and treatment resistance."	1.36	Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. ( Baumann, B; Büchler, MW; Gladkich, J; Herr, I; Kallifatidis, G; Liu, L; Mattern, J; Rausch, V; Salnikov, AV; Schemmer, P; Wirth, T; Zöller, M, 2010)
"When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited."	1.36	The telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines. ( Bassett, E; Buseman, CM; Go, NF; Harley, C; Joseph, I; Pattamatta, P; Shay, JW; Tressler, R; Wright, WE, 2010)
"Sorafenib is a multikinase inhibitor that has shown promising therapeutic results in different tumor histotypes, both as a single agent or in combination with other treatments."	1.35	Role of RAF/MEK/ERK pathway, p-STAT-3 and Mcl-1 in sorafenib activity in human pancreatic cancer cell lines. ( Amadori, D; Arienti, C; Carloni, S; Fabbri, F; Silvestrini, R; Tesei, A; Ulivi, P; Vannini, I; Zoli, W, 2009)
"In locally advanced esophageal cancer it has been proved that the definitive radiochemotherapy is an alternative at radiochemotherapy plus surgery."	1.35	[News in digestive oncology]. ( Di Fiore, F; Michel, P, 2008)
"In stimulated islet cell tumors, an increase of PA was visible in the microsomal fraction, and there was an increase of lysophosphatidylcholine in the mitochondrial fraction."	1.29	Lipid composition of glucose-stimulated pancreatic islets and insulin-secreting tumor cells. ( Lenzen, S; Matthies, A; Rustenbeck, I, 1994)
"After a long latency, hormone-producing islet cell tumors are induced with high frequency by a single administration of streptozotocin and nicotinamide in the rats."	1.27	Streptozotocin-induced functioning islet cell tumor in the rat: high frequency of induction and biological properties of the tumor cells. ( Bergamini, E; Blondel, B; Gori, Z; Masiello, P; Wollheim, CB, 1984)
"Pancreatic islet cell tumors were induced in 38 of 44 male Wistar rats (86%), which survived 9 to 14 months following the various treatment schedules."	1.26	Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. ( Baba, S; Fujii, S; Kazumi, T; Yoshino, G, 1978)
"Pancreatic islet cell tumors were induced in 32 of 49 male Wistar rats (73%) surviving 9 months or longer following treatment with streptozotocin alone, with streptozotocin and nicotinamide, or with streptozotocin and picolinamide."	1.26	Biochemical studies on rats with insulin-secreting islet cell tumors induced by streptozotocin: with special reference to physiological response to oral glucose load in the course of and after tumor induction. ( Baba, S; Doi, K; Kaneko, S; Kazumi, T; Yoshida, M; Yoshida, Y; Yoshino, G, 1978)
"At that time pancreatic islet cell tumors were demonstrated in all of the rats in this experiment."	1.26	Glucagon secretion during the development of insulin-secreting tumors induced by streptozotocin and nicotinamide. ( Baba, S; Kazumi, T; Kobayashi, N; Morita, S; Terashi, K; Yoshino, G, 1979)

Research

Studies (99)

Authors

Clinical Trials (6)

Trial Overview

Trial Outcomes

Phase II: Overall Survival (OS) Time

Timeframe	Studies, this research(%)	All Research%
pre-1990	33 (33.33)	18.7374
1990's	4 (4.04)	18.2507
2000's	9 (9.09)	29.6817
2010's	50 (50.51)	24.3611
2020's	3 (3.03)	2.80

Authors	Studies
Kuang, Y	1
Ye, N	1
Kyani, A	1
Ljungman, M	1
Paulsen, M	1
Chen, H	2
Zhou, M	1
Wild, C	1
Zhou, J	1
Neamati, N	1
Qadir, MI	1
Iqbal, MS	1
Khan, R	1
Spencer, KR	1
Portal, DE	1
Aisner, J	1
Stein, MN	1
Malhotra, J	1
Shih, W	1
Chan, N	1
Silk, AW	1
Ganesan, S	1
Goodin, S	1
Gounder, M	1
Lin, H	1
Li, J	1
Cerchio, R	1
Marinaro, C	1
Chen, S	1
Mehnert, JM	1
Yang, J	2
Jia, B	1
Yan, J	1
He, J	1
Van Cutsem, E	1
Hidalgo, M	1
Canon, JL	1
Macarulla, T	1
Bazin, I	1
Poddubskaya, E	1
Manojlovic, N	1
Radenkovic, D	1
Verslype, C	1
Raymond, E	1
Cubillo, A	1
Schueler, A	1
Zhao, C	1
Hammel, P	1
Fang, Z	1
Jung, KH	2
Yan, HH	2
Kim, SJ	1
Rumman, M	1
Park, JH	1
Han, B	1
Lee, JE	1
Kang, YW	1
Lim, JH	1
Hong, SS	2
Pawaskar, DK	3
Straubinger, RM	3
Fetterly, GJ	3
Hylander, BH	2
Repasky, EA	2
Ma, WW	3
Jusko, WJ	3
Awasthi, N	1
Zhang, C	1
Hinz, S	1
Schwarz, MA	1
Schwarz, RE	1
Sarris, EG	1
Syrigos, KN	1
Saif, MW	3
Stenzinger, A	1
Endris, V	1
Klauschen, F	1
Sinn, B	1
Lorenz, K	1
Warth, A	1
Goeppert, B	1
Ehemann, V	1
Muckenhuber, A	1
Kamphues, C	1
Bahra, M	1
Neuhaus, P	1
Weichert, W	1
Cascinu, S	2
Berardi, R	2
Sobrero, A	2
Bidoli, P	1
Labianca, R	2
Siena, S	1
Ferrari, D	2
Barni, S	3
Aitini, E	2
Zagonel, V	1
Caprioni, F	2
Villa, F	1
Mosconi, S	2
Faloppi, L	2
Tonini, G	2
Boni, C	2
Conte, P	1
Di Costanzo, F	1
Cinquini, M	2
Hescot, S	1
Baudin, E	1
Borson-Chazot, F	1
Lombès, M	1
Aparicio, J	1
García-Mora, C	1
Martín, M	1
Petriz, ML	1
Feliu, J	1
Sánchez-Santos, ME	1
Ayuso, JR	1
Fuster, D	1
Conill, C	1
Maurel, J	1
Cardin, DB	1
Goff, L	1
Li, CI	1
Shyr, Y	1
Winkler, C	1
DeVore, R	1
Schlabach, L	1
Holloway, M	1
McClanahan, P	1
Meyer, K	1
Grigorieva, J	1
Berlin, J	1
Chan, E	1
Jafary, H	1
Ahmadian, S	1
Soleimani, M	1
Chiorean, EG	2
Schneider, BP	1
Akisik, FM	1
Perkins, SM	1
Anderson, S	1
Johnson, CS	1
DeWitt, J	1
Helft, P	1
Clark, R	1
Johnston, EL	1
Spittler, AJ	1
Deluca, J	1
Bu, G	2
Shahda, S	1
Loehrer, PJ	1
Sandrasegaran, K	2
Cardenes, HR	1
Graham, U	1
Eatock, M	1
Atkinson, B	1
Bi, HC	1
Pan, YZ	1
Qiu, JX	1
Krausz, KW	1
Li, F	1
Johnson, CH	1
Jiang, CT	1
Gonzalez, FJ	1
Yu, AM	1
Li, Y	1
Tang, K	1
Zhang, L	1
Li, C	1
Niu, F	1
Zhou, W	1
Yang, H	1
Feng, Z	1
Chen, X	1
Makielski, RJ	1
Lubner, SJ	2
Mulkerin, DL	2
Traynor, AM	2
Groteluschen, D	2
Eickhoff, J	1
LoConte, NK	2
Vena, F	1
Li Causi, E	1
Rodriguez-Justo, M	1
Goodstal, S	1
Hagemann, T	1
Hartley, JA	1
Hochhauser, D	1
Bianconi, M	1
Giampieri, R	1
Zaniboni, A	1
Fanello, S	1
Bittoni, A	1
Andrikou, K	1
Torri, V	1
Scartozzi, M	1
Liao, J	2
Hwang, SH	2
Li, H	2
Yang, Y	1
Wecksler, AT	1
Liu, JY	2
Hammock, BD	2
Yang, GY	2
Ulivi, P	2
Arienti, C	2
Amadori, D	2
Fabbri, F	2
Carloni, S	2
Tesei, A	2
Vannini, I	1
Silvestrini, R	2
Zoli, W	2
Wang, ZY	1
Huang, S	1
Sinicrope, FA	1
Wei, G	1
Wang, M	1
Carr, BI	1
Plentz, RR	1
Manns, MP	1
Greten, TF	1
Beljanski, V	1
Knaak, C	1
Zhuang, Y	1
Smith, CD	1
Scarsella, M	1
Chiadini, E	1
Orlandi, A	1
Passeri, D	1
Zupi, G	1
Milandri, C	1
Leonetti, C	1
Akisik, MF	1
Lin, C	1
Hutchins, GD	1
Rausch, V	1
Liu, L	1
Kallifatidis, G	1
Baumann, B	1
Mattern, J	1
Gladkich, J	1
Wirth, T	1
Schemmer, P	1
Büchler, MW	1
Zöller, M	1
Salnikov, AV	1
Herr, I	1
Beck, J	1
Bellmunt, J	1
Escudier, B	1
Ricciardi, S	1
Mey, V	1
Nannizzi, S	1
Pasqualetti, G	1
Crea, F	1
Del Tacca, M	1
Danesi, R	1
Kindler, HL	1
Wroblewski, K	1
Wallace, JA	1
Hall, MJ	1
Locker, G	1
Nattam, S	1
Agamah, E	1
Stadler, WM	1
Vokes, EE	1
Joseph, I	1
Tressler, R	1
Bassett, E	1
Harley, C	1
Buseman, CM	1
Pattamatta, P	1
Wright, WE	1
Shay, JW	1
Go, NF	1
Fratto, ME	1
Santini, D	1
Vincenzi, B	1
Silvestris, N	1
Azzariti, A	1
Tommasi, S	1
Zoccoli, A	1
Galluzzo, S	1
Maiello, E	1
Colucci, G	1
Petrelli, F	1
Ghilardi, M	1
Colombo, S	1
Stringhi, E	1
Barbara, C	1
Cabiddu, M	1
Elia, S	1
Corti, D	1
Oberstein, PE	1
El-Khoueiry, AB	1
Ramanathan, RK	1
Yang, DY	1
Zhang, W	1
Shibata, S	1
Wright, JJ	1
Gandara, D	1
Lenz, HJ	1
Allen, E	1
Walters, IB	1
Hanahan, D	1
Jeong, HK	1
Roh, SY	1
Hong, SH	1
Won, HS	1
Jeon, EK	1
Shin, OR	1
Lee, SL	1
Ko, YH	1
Liu, H	1
Zhang, T	1
Chen, R	1
McConkey, DJ	1
Ward, JF	1
Curley, SA	1
Wei, F	1
Liu, Y	1
Bellail, AC	1
Olson, JJ	1
Sun, SY	1
Lu, G	1
Ding, L	1
Yuan, C	1
Wang, G	1
Hao, C	1
Ying, JE	1
Zhu, LM	1
Liu, BX	1
Alzahrani, AS	1
AlQaraawi, A	1
Al Sohaibani, F	1
Almanea, H	1
Abalkhail, H	1
Gonçalves, A	1
Gilabert, M	1
François, E	1
Dahan, L	1
Perrier, H	1
Lamy, R	1
Re, D	1
Largillier, R	1
Gasmi, M	1
Tchiknavorian, X	1
Esterni, B	1
Genre, D	1
Moureau-Zabotto, L	1
Giovannini, M	1
Seitz, JF	1
Delpero, JR	1
Turrini, O	1
Viens, P	1
Raoul, JL	1
Naraev, BG	1
Strosberg, JR	1
Halfdanarson, TR	1
Holen, KD	1
Schelman, WR	1
Deming, DA	1
Hernan, HR	1
Goggins, T	1
Oettel, K	1
Robinson, E	1
Yun, SM	1
Lee, H	1
Son, MK	1
Seo, JH	1
Park, BH	1
Hong, S	1
Fendrich, V	1
Maschuw, K	1
Rehm, J	1
Buchholz, M	1
Holler, JP	1
Slater, EP	1
Bartsch, DK	1
Waldmann, J	1
Siu, LL	1
Awada, A	1
Takimoto, CH	1
Piccart, M	1
Schwartz, B	1
Giannaris, T	1
Lathia, C	1
Petrenciuc, O	1
Moore, MJ	1
Von Hoff, DD	1
Robinson, SI	1
Hobday, TJ	1
Sathananthan, A	1
Morris, JC	1
McWilliams, RR	1
Michel, P	1
Di Fiore, F	1
Burris, H	1
Rocha-Lima, C	1
Johnson, DE	3
Dixit, PK	7
Michels, JE	3
Bauer, GE	7
Masiello, P	1
Wollheim, CB	1
Gori, Z	1
Blondel, B	1
Bergamini, E	1
Morohoshi, T	1
Kanda, M	1
Klöppel, G	2
Pour, PM	2
Lawson, T	1
Chick, WL	1
Appel, MC	1
Weir, GC	1
Like, AA	1
Lauris, V	1
Porter, JG	1
Chute, RN	1
Kazumi, T	9
Yoshino, G	8
Baba, S	8
Yagihashi, S	1
Nagai, K	1
Morita, S	3
Kobayashi, N	2
Terashi, K	2
Younoszai, R	1
Hegre, O	1
Yamamoto, H	2
Okamoto, H	2
Williams, FG	2
Sakamoto, C	1
Otsuki, M	1
Ohki, A	1
Yamasaki, T	1
Yuu, H	1
Maeda, M	1
Rustenbeck, I	1
Matthies, A	1
Lenzen, S	2
Baczako, K	1
Dolderer, M	1
Knip, M	1
Douek, IF	1
Moore, WP	1
Gillmor, HA	1
McLean, AE	1
Bingley, PJ	1
Gale, EA	1
Kim, KA	1
Kim, S	1
Chang, I	1
Kim, GS	1
Min, YK	1
Lee, MK	1
Kim, KW	1
Lee, MS	1
Doi, K	2
Schoental, R	1
Korec, R	1
Fujii, S	2
Yoshida, Y	2
Yoshida, M	1
Kaneko, S	1
Taniguchi, H	1
Villada, G	1
Chosidow, O	1
Delchier, JC	1
Clérici, T	1
Cordoliani, F	1
Wolkenstein, P	1
Roujeau, JC	1
Revuz, J	1
Dunne, MJ	1
Sorenson, RL	1
Wobken, JD	1
Bell, RH	1
McCullough, PJ	1
Yamagami, T	1
Miwa, A	1
Takasawa, S	1
Zielmann, S	1
Panten, U	1
Johnson, D	1
Horányi, J	1
Keszthelyi, LM	1
Kiss, IB	1
Gerö, L	1
Duffek, L	1
Totpál, G	1
Alánt, O	1
Hirose, Y	1
Ishihara, K	1
Makimura, H	1
Utsumi, M	1
Rakieten, N	1
Gordon, BS	1

Trial	Phase	Enrollment	Study Type	Start Date	Status
Phase II Randomized Trial of MEK Inhibitor MSC1936369B or Placebo Combined With Gemcitabine in Metastatic Pancreas Cancer Subjects[NCT01016483]	Phase 1/Phase 2	141 participants (Actual)	Interventional	2009-11-30	Completed
Open-label, Multicentric Phase I-II Trial to Evaluate the Efficacy and Safety of the Combination of Sorafenib (BAY 43-9006), Gemcitabine and Concurrent Radiotherapy, in Locally Advanced Pancreatic Carcinoma[NCT00789763]	Phase 1	12 participants (Actual)	Interventional	2007-12-31	Completed
Stereotactic Body Radiation Therapy Plus Pembrolizumab and Trametinib vs. Stereotactic Body Radiation Therapy Plus Gemcitabine for Locally Recurrent Pancreatic Cancer After Surgical Resection: an Open-label, Randomized, Controlled, Phase 2 Trial[NCT02704156]	Phase 2	170 participants (Actual)	Interventional	2016-10-31	Completed
Evaluation of the Effect of Ocoxin-Viusid® Nutritional Supplement in the Life Quality in Patients Diagnosed With Advanced Pancreatic Adenocarcinoma. Phase II[NCT03717298]	Phase 2	30 participants (Actual)	Interventional	2018-10-30	Completed
Three-Day Dosing NAD + Study[NCT03707652]		8 participants (Actual)	Interventional	2018-03-12	Completed
Randomized Double-blinded Comparative Trial to Study the Add-on Activity of Combination Treatment of Nicotinamide on Progression Free Survival for EGFR Mutated Lung Cancer Terminal Stage Patients Being Treated With Gefitinib or Erlotinib[NCT02416739]	Phase 2/Phase 3	110 participants (Actual)	Interventional	2015-03-31	Active, not recruiting
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Overall survival (OS) time is defined as the time (in months) from randomization to death. (NCT01016483)
Timeframe: Baseline, every 8 weeks up to EOT (6 years)

Phase II: Percentage of Subjects With Clinical Benefit

Intervention	months (Median)
Phase II: Arm 1	6.64
Phase II: Arm 2	9.33

Clinical Benefit was defined as the presence of at least one CR, PR or Stable Disease (SD) (using RECIST v1.0) during treatment. CR: Disappearance of all target lesions, PR: At least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline and 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 treatment started. (NCT01016483)
Timeframe: Baseline, every 8 weeks up to end of treatment (EOT i.e. 6 years)

Phase II: Progression-Free Survival (PFS) Time

Intervention	percentage of subjects (Number)
Phase II: Arm 1	45.5
Phase II: Arm 2	59.1

PFS was defined as the time from randomization to the first documentation of objective tumor progression (Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline, Progressive Disease (PD): At least 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 and stable disease: 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 treatment started) or to death due to any cause, whichever occurred first. PFS calculated as (Months) = Date of first PD or death or censoring date minus date of randomization plus 1) divided by 30.4375. (NCT01016483)
Timeframe: From the time of randomization to every 8 weeks up to end of treatment (EOT) (6 years)

Phase II: Time to Progression (TTP)

Intervention	months (Median)
Phase II: Arm 1	2.83
Phase II: Arm 2	3.75

Time to progression (TTP) is defined as the time (in months) from the randomization date to the date of progression prior to the start of any subsequent therapy for the primary disease, as reported and documented by the Investigator (i.e. radiological progression per RECIST). (NCT01016483)
Timeframe: From randomization every 8 weeks up to EOT (6 years)

Safety Run-In Part: Number of Subjects With Dose Limiting Toxicities (DLTs)

Intervention	months (Median)
Phase II: Arm 1	3.78
Phase II: Arm 2	5.09

DLT using the National Cancer Institute Common Terminology Criteria for Adverse Events(CTCAE) v3.0,was defined as any of the following toxicities at any dose level and judged to be possibly or probably related to trial medication by the Investigator and/or the Sponsor and relevant for the combination treatment: Grade 3/more non-hematological toxicity excluding: Subjects with liver involvement: Grade 4 asymptomatic increases in liver function tests and subject without liver involvement: Grade 3 asymptomatic increases in liver function tests reversible within 7 days. Grade 3 vomiting encountered despite adequate therapy. Grade 3 diarrhea encountered despite adequate anti diarrhea therapy. Grade 4 neutropenia greater (>) 5 days duration or febrile neutropenia lasting for more than 1 day. Grade 4 thrombocytopenia > 1 day/Grade 3 with bleeding. Grade 4 anemia: Any treatment delay > 2 weeks due to drug-related adverse effects. (NCT01016483)
Timeframe: Up to 28 days in Cycle 1

Phase II: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation

Intervention	subjects (Number)
Safety Run-in Part Regimen 1: 15 mg	0
Safety Run-in Part Regimen 1: 30 mg	0
Safety Run-in Part Regimen 1: 45 mg	0
Safety Run-in Part Regimen 1: 68 mg	0
Safety Run-in Part Regimen 1: 90 mg	0
Safety Run-in Part Regimen 1: 120 mg	0
Safety Run-in Part Regimen 2: 60 mg	1
Safety Run-in Part Regimen 2: 75 mg	2

An AE was any untoward medical occurrence in a subject 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. All AEs (serious and non-serious) except AEs recorded with an onset date prior to the first day of drug administration unless a worsening of the event was recorded after the first dosing date, in which case the event was counted as a TEAE. TEAEs include both SAEs and non-SAEs. (NCT01016483)
Timeframe: From the first dose of study drug administration until EOT (6 years)

Phase II: Percentage of Subjects With Best Overall Response (BOR)

Intervention	subjects (Number)
	TEAEs	Serious TEAEs	TEAEs Leading to Treatment Discontinuation
Phase II: Arm 1	40	28	10
Phase II: Arm 2	45	35	21

Best overall response was defined as the presence of at least one complete response (CR), partial response (PR) or Stable Disease (SD) (using RECIST v1.0) during treatment. CR: Disappearance of all target lesions, PR: At least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the sum of the longest diameter at baseline and 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 treatment started. (NCT01016483)
Timeframe: Baseline, every 8 weeks up to end of treatment (EOT i.e. 6 years)

Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 1

Intervention	percentage of subjects (Number)
	CR	PR	SD	PD	Missing
Phase II: Arm 1	0	9.1	36.4	29.5	25
Phase II: Arm 2	0	9.1	50.0	20.5	20.5

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) was influenced by the fraction of the dose absorbed. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 2

Intervention	Liter per hour (L/h) (Geometric Mean)
	CL/f: MSC1936369B on Day 1 (n=4,3,3,2,3,11)	CL/f: MSC1936369B on Day 22 (n=2,2,3,2,3,9)
Regimen 1: 120 mg	55.171	55.723
Regimen 1: 30 mg	58.104	42.484
Regimen 1: 45 mg	51.072	44.579
Regimen 1: 68 mg	87.765	56.502
Regimen 1: 90 mg	52.025	50.873
Regimen 1:15 mg	92.152	74.143

Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 1

Intervention	Liter per hour (L/H) (Geometric Mean)
	CL/f: MSC1936369B on Day 1 (n=10,11)	CL/f: MSC1936369B on Day 22 (n=8,5)
Regimen 2: 60 mg	85.186	70.163
Regimen 2: 75 mg	52.558	68.312

Apparent volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 2

Intervention	liter (Geometric Mean)
	V: Gemcitabine (dFdC) on Day 1 (n= 4,3,3,3,3,11)	V: Gemcitabine (dFdC) on Day 22 (n=2,2,1,2,2,9)
Regimen 1: 120 mg	1270.1	805.15
Regimen 1: 15 mg	359.55	1723.6
Regimen 1: 30 mg	531.23	908.50
Regimen 1: 45 mg	587.64	251.79
Regimen 1: 68 mg	729.65	149.65
Regimen 1: 90 mg	2402.1	2140.8

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. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Area Under Curve (AUC: 0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1

Intervention	liter (Geometric Mean)
	V: Gemcitabine on Day 1 (n=11,14)	V: Gemcitabine on Day 22 (n=9,4)
Regimen 2: 60 mg	716.12	1590.8
Regimen 2: 75 mg	1059.0	801.90

AUC:0 to infinity was a measure of the serum concentration of the drug over time. It was used to characterize drug absorption. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1 of Cycle 1 for MSC1936369B, 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1 for Gemcitabine

Safety Run-In Part: Area Under Curve (AUC:0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) Regimen 2

Intervention	hournanogram per milliliter (hng/mL) (Geometric Mean)
	AUC: MSC1936369B on Day 1 (n=4,3,3,3,3,11)	AUC: Gemcitabine (dFdC) on Day 1(n=4,3,3,3,3,11)	AUC: Gemcitabine (dFdC) on Day 22(n=2,2,1,2,2,9)	AUC: Metabolite (dFdU) on Day 1 (n=4,3,3,3,3,11)	AUC: Metabolite (dFdU) on Day 22 (n=2,2,2,2,2,10)
Regimen 1: 30 mg	516.3	13536.5	12019.6	228032.9	376280.5
Regimen 1: 45 mg	881.1	10053.3	9093.2	276968.3	217930.8
Regimen 1: 68 mg	774.8	18956.0	76448.7	259816.2	327424.8
Regimen 1: 90 mg	1729.9	8178.4	9604.8	239902.9	248496.4
Regimen 1:15 mg	162.8	29536.1	10828.0	245795.5	190952.6
Regimen1: 120 mg	2175.1	11680.1	10598.0	240293.8	247430.7

AUC:0 to infinity is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1 of Cycle 1 for MSC1936369B, 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1 for Gemcitabine

Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 1

Intervention	hournanogram per milliliter (hng/mL) (Geometric Mean)
	AUC: MSC1936369B on Day 1 (n= 10, 11)	AUC: Gemcitabine (dFdC) on Day 1 (n= 11, 14)	AUC: Gemcitabine (dFdC) on Day 22 (n= 9, 4)	AUC: Metabolite (dFdU) on Day 1 (n= 11, 13)	AUC: Metabolite (dFdU) on Day 22 (n= 10, 5)
Regimen 1: 75 mg	1427.0	8065.5	10102.3	234934.8	256714.9
Regimen 2: 60 mg	704.3	11932.0	10719.1	189007.0	177504.5

ERK phosphoprotein in peripheral blood monocytes (PBMCs) was analyzed from blood samples of all subjects in the SAF analysis set (safety-run part) only. (NCT01016483)
Timeframe: pre-dose on Day 1, 2, 22 of Cycle 1; post-dose on Day 1, 22 of Cycle 1

Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 2

Intervention	Fluorescence Intensity (Mean)
	Cycle 1 Day 1 Pre-dose (n=3,2,2,3,3,7)	Cycle 1 Day 1 Post-dose (n=3,2,2,3,2,6)	Cycle 1 Day 2 Pre-dose (n=3,2,1,2,2,6)	Cycle 1 Day 22 Pre-dose (n=2,1,2,1,3,5)	Cycle 1 Day 22 Post-dose (n=0,0,0,0,2)
Regimen 1: 30 mg	6.476	2.061	6.719	6.000	NA
Regimen 1: 45 mg	4.767	0.837	3.902	1.978	NA
Regimen 1: 68 mg	6.509	3.881	2.768	8.653	NA
Regimen 1: 90 mg	4.608	1.059	4.874	4.252	NA
Regimen 1:15 mg	5.389	1.611	4.818	5.242	NA
Regimen1: 120 mg	4.229	0.946	3.636	3.453	4.130

Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) for Regimen 1

Intervention	Fluorescence Intensity (Mean)
	Cycle 1 Day 1 Pre-dose (n=7,4)	Cycle 1 Day 1 Post-dose (n=5,3)	Cycle 1 Day 2 Pre-dose (n=7,3)	Cycle 1 Day 22 Pre-dose (n=6,2)	Cycle 1 Day 22 Post-dose (n=3,1)
Regimen 2: 60 mg	6.081	1.520	3.877	2.728	1.443
Regimen 2: 75 mg	5.874	1.048	2.263	2.295	1.111

(NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2

Intervention	nanogram per milliliter (ng/mL) (Geometric Mean)
	MSC1936369B on Days 1 (n=4,3,3,3,3,11)	MSC1936369B on Days 22 (n= 3,3,3,2,3,10)	Gemcitabine (dFdC) on Day 1 (n=4,3,3,3,3,11)	Gemcitabine (dFdC) on Day 22 (n= 2,3,3,2,3,9)	Metabolite (dFdU) on Day 1 (n= 4,3,3,3,3,11)	Metabolite (dFdU) on Day 22 (n= 2,3,3,2,3,10)
Regimen 1: 120 mg	484.3	252.9	23880.7	23207.2	34038.7	21077.5
Regimen 1: 15 mg	32.3	29.6	69540.5	24115.8	29359.8	29677.6
Regimen 1: 30 mg	131.0	174.2	21207.3	11799.7	33171.6	38265.2
Regimen 1: 45 mg	205.8	261.8	17759.9	181.9	34868.9	10569.2
Regimen 1: 68 mg	151.3	212.5	29762.1	163196.2	33804.4	32869.2
Regimen 1: 90 mg	485.3	409.1	15606.3	669.5	37786.4	17135.0

(NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation

Intervention	nanogram per milliliter (ng/mL) (Geometric Mean)
	MSC1936369B on Day 1 (n= 12,13)	MSC1936369B on Day 22 (n=10,9)	Gemcitabine (dFdC) on Day 1 (n=11,14)	Gemcitabine (dFdC) on Day 22 (n=9,4)	Gemcitabine Metabolite (dFdU) on Day 1 (n=11, 10)	Gemcitabine Metabolite (dFdU) on Day 22 (n=10,5)
Regimen 2: 60 mg	175.7	228.2	27849.2	21589.7	33033.3	13455.5
Regimen 2: 75 mg	345.5	244.8	17663.9	18733.4	31623.9	18298.7

An adverse event (AE) was any untoward medical occurrence in a subjects 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 inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. All AEs (serious and non-serious) except AEs recorded with an onset date prior to the first day of drug administration unless a worsening of the event was recorded after the first dosing date, in which case the event was counted as a TEAE. TEAEs include both SAEs and non-SAEs. (NCT01016483)
Timeframe: From the first dose of study drug administration until EOT (6 years)

Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 1

Intervention	subjects (Number)
	TEAEs	Serious TEAEs	Permanent treatment discontinuation of pimasertib	Permanent treatment discontinuation of gemcitabine
Safety Run-in Part: Regimen 1	27	18	12	14
Safety Run-in Part: Regimen 2	26	20	16	15

Volume of distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 2

Intervention	liter (Geometric Mean)
	V/f: MSC1936369B on Day 1 (n=4,3,3,2,3,11)	V/f: MSC1936369B on Day 22 (n=2,2,3,2,3,8)
Regimen 1: 120 mg	367.25	414.38
Regimen 1: 15 mg	528.62	824.33
Regimen 1: 30 mg	369.12	366.30
Regimen 1: 45 mg	329.80	264.31
Regimen 1: 68 mg	524.96	441.40
Regimen 1: 90 mg	362.29	284.42

Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1

Intervention	liter (Geometric Mean)
	V/f: MSC1936369B on Day 1 (n= 10,11)	V/f: MSC1936369B on Day 22 (n=8,5)
Regimen 2: 60 mg	335.56	389.56
Regimen 2: 75 mg	213.24	319.02

Plasma decay half-life was the time measured for the plasma concentration to decrease by one half. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2

Intervention	hours (Median)
	t1/2: MSC1936369B on Day 1 (n=4,3,3,2,3,11)	t1/2: MSC1936369B on Day 22 (n=2,2,3,2,3,8)	t1/2: Gemcitabine (dFdC) on Day 1 (n=4,3,3,3,3,11)	t1/2: Gemcitabine (dFdC) on Day 22 (n=2,2,1,2,2,9)	t1/2: Metabolite (dFdU) on Day 1 (n=4,3,3,3,3,11)	t1/2: Metabolite (dFdU) on Day 22(n=2,2,2,2,2,10)
Regimen 1: 120 mg	4.580	4.825	6.242	4.680	10.93	12.17
Regimen 1: 15 mg	4.008	8.660	4.274	7.449	8.956	7.731
Regimen 1: 30 mg	3.807	6.100	2.461	4.553	10.49	8.925
Regimen 1: 45 mg	3.833	3.254	2.421	0.9152	9.836	8.843
Regimen 1: 68 mg	4.232	5.744	5.327	4.493	11.52	11.14
Regimen 1: 90 mg	5.036	3.162	8.940	8.213	8.349	10.21

Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1

Intervention	hours (Median)
	t1/2: MSC1936369B on Day 1 (n=10,11)	t1/2: MSC1936369B on Day 22 (n=8,5)	t1/2: Gemcitabine (dFdC) on Day 1 (n=11,14)	t1/2: Gemcitabine (dFdC) on Day 22 (n=9,4)	t1/2: Metabolite (dFdU) on Day 1 (n=11,13)	t1/2: Metabolite (dFdU) on Day 22 (n=10,5)
Regimen 2: 60 mg	2.757	3.425	5.258	5.522	9.471	10.68
Regimen 2: 75 mg	2.603	3.188	5.376	5.249	10.26	13.58

(NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2

Intervention	hours (Median)
	Tmax: MSC1936369B on Day 1 (n= 4,3,3,3,3,11)	Tmax: MSC1936369B on Day 22 (n= 3,3,3 2,3,10)	Tmax: Gemcitabine (dFdC) on Day 1 (n=4,3,3,3,3,11)	Tmax: Gemcitabine (dFdC) on Day 22 (n=2,3,3,2,3,9)	Tmax: Metabolite (dFdU) on Day 1 (n=4,3,3,3,3,11)	Tmax: Metabolite (dFdU) on Day 22 (n=2,3,3,2,3,10
Regimen 1: 120 mg	1.500	2.000	0.27	0.50	0.50	0.75
Regimen 1: 15 mg	1.250	2.017	0.38	0.42	0.64	0.54
Regimen 1: 30 mg	1.000	1.000	0.50	0.50	0.50	0.75
Regimen 1: 45 mg	1.533	1.000	0.25	0.53	0.50	1.00
Regimen 1: 68 mg	2.000	1.750	0.25	1.04	0.75	0.67
Regimen 1: 90 mg	1.083	1.500	0.25	0.25	0.50	0.75

(NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 1

Intervention	hours (Median)
	Tmax: MSC1936369B on Day 1 (n=12,13)	Tmax: MSC1936369B on Day 22 (n=10,9)	Tmax: Gemcitabine (dFdC) on Day 1 (n=11,14)	Tmax: Gemcitabine (dFdC) on Day 22 (n=9,4)	Tmax: Metabolite (dFdU) on Day 1 (n=11,13)	Tmax: Metabolite (dFdU) on Day 22 (n=10,5)
Regimen 2: 60 mg	2.000	1.500	0.50	0.25	0.67	0.50
Regimen 2: 75 mg	1.583	2.000	0.38	0.25	0.67	0.50

Clearance of a drug was a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. (NCT01016483)
Timeframe: 0 hour (pre-dose), 0.5, 1, 1.5, 2, 2.5, 4, 8, 12, 24 (post-dose) on Day 1, 22 of Cycle 1

Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 2

Intervention	liter/hour (Geometric Mean)
	CL: Gemcitabine on Day 1 (n=4,3,3,3,3,11)	CL: Gemcitabine on Day 22 (n=2,2,1,2,2,9)
Regimen 1: 120 mg	151.93	164.6
Regimen 1: 15 mg	60.537	163.37
Regimen 1: 30 mg	133.88	156.93
Regimen 1: 45 mg	190.52	190.69
Regimen 1: 68 mg	95.96	25.123
Regimen 1: 90 mg	210.25	183.97

The Median Progression Free Survival Time Will be Determined.

Intervention	liter/hour (Geometric Mean)
	CL: Gemcitabine on Day 1 (n=11, 14)	CL: Gemcitabine on Day 22 (n=9, 4)
Regimen 2: 60 mg	145.65	164.68
Regimen 2: 75 mg	221.46	183.85

The time from the start of treatment until documentation of any clinical or radiological disease progression or death, whichever occurred first. Progression is assessed by the 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. (NCT02704156)
Timeframe: 3 years

The Median Survival Time Will be Determined.

One- and Two-year Overall Survival Rate Will be Determined.

Intervention	months (Median)
SBRT Plus Gemcitabine	5.4
SBRT Plus Pembrolizumab and Trametinib	8.2

Intervention	months (Median)
SBRT Plus Gemcitabine	12.8
SBRT Plus Pembrolizumab and Trametinib	14.9

The number of patients alive at 1 year and 2 years. (NCT02704156)
Timeframe: 2 year

One- and Two-year Progression Survival Rate Will be Determined. Will be Determined.

Intervention	Participants (Count of Participants)
	1-year OS rate	2-year OS rate
SBRT Plus Gemcitabine	48	0
SBRT Plus Pembrolizumab and Trametinib	53	2

The proportion of patients without disease progressions at 1 year and 2 years. (NCT02704156)
Timeframe: 2 years

The Quality of Life Will be Analyzed.

Intervention	Participants (Count of Participants)
	1-year PFS rate	2-year PFS rate
SBRT Plus Gemcitabine	7	0
SBRT Plus Pembrolizumab and Trametinib	18	0

The analysis of quality of life is based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30). All scales and subscales range from 0 to 100. Regarding physical functioning, role functioning, emotional functioning, cognitive functioning, social functioning and global health, higher scores may indicate better outcomes. In the case of fatigue, nausea and vomitting, pain, dyspnea, insomina, appetite loss, constipation, diarrhea and financial difficulties, lower scores may indicate better outcomes. Scales of all items are independent and not combined to compute a total score. (NCT02704156)
Timeframe: 3 years

Treatment-related Adverse Effects Will be Determined.

Intervention	units on a scale (Mean)
	Physical functioning	Role functioning	Emotional functioning	Cognitive functioning	Social functioning	Global health	Fatigue	Nausea and vomitting	Pain	Dyspnea	Insomina	Appetite loss	Constipation	Diarrhea	Financial difficulties
SBRT Plus Gemcitabine	86.2	81.8	73.9	84.7	85.5	83.6	29.6	29.4	23.9	16.1	14.9	31.0	14.5	15.7	16.8
SBRT Plus Pembrolizumab and Trametinib	83.7	84.5	72.1	83.3	84.1	83.2	26.6	28.8	26.5	13.7	17.6	33.3	16.5	15.7	17.2

Treatment-related adverse effects are determined by National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0. (NCT02704156)
Timeframe: 3 years

Intervention	Participants (Count of Participants)
	Grade 3 pyrexia	Grade 3 vomitting	Grade 3 and 4 increased ALT or AST	Grade 3 stomatitis	Grade 3 rash	Grade 3 and 4 neutropenia	Grade 3 thrombocytopenia	Grade 3 increased blood bilirubin	Grade 3 hypokalemia	Grade 3 hyponatremia	Grade 3 pneumonia	Grade 3 hypertension
SBRT Plus Gemcitabine	0	2	6	0	0	9	4	0	0	0	0	0
SBRT Plus Pembrolizumab and Trametinib	2	1	10	1	2	1	1	4	1	3	1	2

Article	Year
[Targeted therapies, prognostic and predictive factors in endocrine oncology]. Annales d'endocrinologie, 2013, Volume: 74 Suppl 1 Topics: Antineoplastic Agents; Carcinoma, Neuroendocrine; Clinical Trials, Phase III as Topic; Disease-Free	2013
[Bemusement and strategy on the efficacy of clinical application of targeted anticancer drugs]. Zhonghua zhong liu za zhi [Chinese journal of oncology], 2009, Volume: 31, Issue:9 Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites,	2009
Molecular therapy of pancreatic cancer. Minerva endocrinologica, 2010, Volume: 35, Issue:1 Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Prot	2010
In vitro and in vivo antitumor efficacy of docetaxel and sorafenib combination in human pancreatic cancer cells. Current cancer drug targets, 2010, Volume: 10, Issue:6 Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates; Docetaxel; Dr	2010
Targeting EGFR in bilio-pancreatic and liver carcinoma. Frontiers in bioscience (Scholar edition), 2011, 01-01, Volume: 3, Issue:1 Topics: Antibodies, Monoclonal; Antineoplastic Agents; Benzenesulfonates; Biliary Tract Neoplasms; Carcinoma	2011
Developments in metastatic pancreatic cancer: is gemcitabine still the standard? World journal of gastroenterology, 2012, Feb-28, Volume: 18, Issue:8 Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates;	2012
Current status and perspectives of targeted therapy in well-differentiated neuroendocrine tumors. Oncology, 2012, Volume: 83, Issue:3 Topics: Antineoplastic Agents; Benzenesulfonates; Cell Differentiation; ErbB Receptors; Everolimus; Histone	2012
What's new in pancreatic cancer treatment pipeline? Best practice & research. Clinical gastroenterology, 2006, Volume: 20, Issue:2 Topics: Adenoviridae; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Benz	2006
New therapeutic directions for advanced pancreatic cancer: targeting the epidermal growth factor and vascular endothelial growth factor pathways. The oncologist, 2008, Volume: 13, Issue:3 Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Benzenes	2008
Safety of high-dose nicotinamide: a review. Diabetologia, 2000, Volume: 43, Issue:11 Topics: Abnormalities, Drug-Induced; Adenoma, Islet Cell; Animals; Chemical and Drug Induced Liver Injury; D	2000
Safety of high-dose nicotinamide: a review. Diabetologia, 2000, Volume: 43, Issue:11 Topics: Abnormalities, Drug-Induced; Adenoma, Islet Cell; Animals; Chemical and Drug Induced Liver Injury; D	2000
Safety of high-dose nicotinamide: a review. Diabetologia, 2000, Volume: 43, Issue:11 Topics: Abnormalities, Drug-Induced; Adenoma, Islet Cell; Animals; Chemical and Drug Induced Liver Injury; D	2000
Safety of high-dose nicotinamide: a review. Diabetologia, 2000, Volume: 43, Issue:11 Topics: Abnormalities, Drug-Induced; Adenoma, Islet Cell; Animals; Chemical and Drug Induced Liver Injury; D	2000

Article	Year
A phase I trial of riluzole and sorafenib in patients with advanced solid tumors: CTEP #8850. Oncotarget, 2023, 04-10, Volume: 14 Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Maximum Tolerated Dose; Neoplasms; Niacinami	2023
Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. International journal of cancer, 2018, 10-15, Volume: 143, Issue:8 Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deox	2018
Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. International journal of cancer, 2018, 10-15, Volume: 143, Issue:8 Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deox	2018
Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. International journal of cancer, 2018, 10-15, Volume: 143, Issue:8 Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deox	2018
Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer. International journal of cancer, 2018, 10-15, Volume: 143, Issue:8 Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deox	2018
Sorafenib does not improve efficacy of chemotherapy in advanced pancreatic cancer: A GISCAD randomized phase II study. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2014, Volume: 46, Issue:2 Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin;	2014
A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study. PloS one, 2014, Volume: 9, Issue:1 Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Thera	2014
Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer. Cancer medicine, 2014, Volume: 3, Issue:3 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Surviva	2014
Phase 1 pharmacogenetic and pharmacodynamic study of sorafenib with concurrent radiation therapy and gemcitabine in locally advanced unresectable pancreatic cancer. International journal of radiation oncology, biology, physics, 2014, Jun-01, Volume: 89, Issue:2 Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemo	2014
A phase II study of sorafenib, oxaliplatin, and 2 days of high-dose capecitabine in advanced pancreas cancer. Cancer chemotherapy and pharmacology, 2015, Volume: 76, Issue:2 Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabin	2015
The value of lactate dehydrogenase serum levels as a prognostic and predictive factor for advanced pancreatic cancer patients receiving sorafenib. Oncotarget, 2015, Oct-27, Volume: 6, Issue:33 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Disease-Free Survival; Fem	2015
Pancreatic cancer: utility of dynamic contrast-enhanced MR imaging in assessment of antiangiogenic therapy. Radiology, 2010, Volume: 256, Issue:2 Topics: Aged; Angiogenesis Inhibitors; Antineoplastic Agents; Benzenesulfonates; Contrast Media; Female; Gad	2010
Gemcitabine plus sorafenib in patients with advanced pancreatic cancer: a phase II trial of the University of Chicago Phase II Consortium. Investigational new drugs, 2012, Volume: 30, Issue:1 Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzenesulf	2012
A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer. Investigational new drugs, 2012, Volume: 30, Issue:3 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; C	2012
BAYPAN study: a double-blind phase III randomized trial comparing gemcitabine plus sorafenib and gemcitabine plus placebo in patients with advanced pancreatic cancer. Annals of oncology : official journal of the European Society for Medical Oncology, 2012, Volume: 23, Issue:11 Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplast	2012
A phase I study of sorafenib, oxaliplatin and 2 days of high dose capecitabine in advanced pancreatic and biliary tract cancer: a Wisconsin oncology network study. Investigational new drugs, 2013, Volume: 31, Issue:4 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocol	2013
Phase I trial of sorafenib and gemcitabine in advanced solid tumors with an expanded cohort in advanced pancreatic cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 2006, Jan-01, Volume: 12, Issue:1 Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; D	2006

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Induction of Genes Implicated in Stress Response and Autophagy by a Novel Quinolin-8-yl-nicotinamide QN523 in Pancreatic Cancer. Journal of medicinal chemistry, 2022, 04-28, Volume: 65, Issue:8 Topics: Antineoplastic Agents; Autophagy; Cell Line, Tumor; Humans; Niacinamide; Pancreatic Neoplasms	2022
Induction of Genes Implicated in Stress Response and Autophagy by a Novel Quinolin-8-yl-nicotinamide QN523 in Pancreatic Cancer. Journal of medicinal chemistry, 2022, 04-28, Volume: 65, Issue:8 Topics: Antineoplastic Agents; Autophagy; Cell Line, Tumor; Humans; Niacinamide; Pancreatic Neoplasms	2022
Induction of Genes Implicated in Stress Response and Autophagy by a Novel Quinolin-8-yl-nicotinamide QN523 in Pancreatic Cancer. Journal of medicinal chemistry, 2022, 04-28, Volume: 65, Issue:8 Topics: Antineoplastic Agents; Autophagy; Cell Line, Tumor; Humans; Niacinamide; Pancreatic Neoplasms	2022
Induction of Genes Implicated in Stress Response and Autophagy by a Novel Quinolin-8-yl-nicotinamide QN523 in Pancreatic Cancer. Journal of medicinal chemistry, 2022, 04-28, Volume: 65, Issue:8 Topics: Antineoplastic Agents; Autophagy; Cell Line, Tumor; Humans; Niacinamide; Pancreatic Neoplasms	2022
β-lapachone: A Promising Anticancer Agent with a Unique NQO1 Specific Apoptosis in Pancreatic Cancer. Current cancer drug targets, 2022, Volume: 22, Issue:7 Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Humans; Mice; NAD(P)H Dehydrogenase (Qu	2022
β-lapachone: A Promising Anticancer Agent with a Unique NQO1 Specific Apoptosis in Pancreatic Cancer. Current cancer drug targets, 2022, Volume: 22, Issue:7 Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Humans; Mice; NAD(P)H Dehydrogenase (Qu	2022
β-lapachone: A Promising Anticancer Agent with a Unique NQO1 Specific Apoptosis in Pancreatic Cancer. Current cancer drug targets, 2022, Volume: 22, Issue:7 Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Humans; Mice; NAD(P)H Dehydrogenase (Qu	2022
β-lapachone: A Promising Anticancer Agent with a Unique NQO1 Specific Apoptosis in Pancreatic Cancer. Current cancer drug targets, 2022, Volume: 22, Issue:7 Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Humans; Mice; NAD(P)H Dehydrogenase (Qu	2022
Glycaemic adverse drug reactions from anti-neoplastics used in treating pancreatic cancer. Nigerian journal of clinical practice, 2017, Volume: 20, Issue:11 Topics: Adverse Drug Reaction Reporting Systems; Antineoplastic Agents; Blood Glucose; China; Deoxycytidine;	2017
Melatonin Synergizes with Sorafenib to Suppress Pancreatic Cancer via Melatonin Receptor and PDGFR-β/STAT3 Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2018, Volume: 47, Issue:5 Topics: Cell Line, Tumor; Drug Synergism; Humans; Melatonin; Neoplasm Proteins; Niacinamide; Pancreatic Neop	2018
Physiologically based pharmacokinetic models for everolimus and sorafenib in mice. Cancer chemotherapy and pharmacology, 2013, Volume: 71, Issue:5 Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Agents; Antineoplastic Combined Chemot	2013
Synergistic interactions between sorafenib and everolimus in pancreatic cancer xenografts in mice. Cancer chemotherapy and pharmacology, 2013, Volume: 71, Issue:5 Topics: Animals; Antineoplastic Agents; Disease Progression; Dose-Response Relationship, Drug; Drug Synergis	2013
Enhancing sorafenib-mediated sensitization to gemcitabine in experimental pancreatic cancer through EMAP II. Journal of experimental & clinical cancer research : CR, 2013, Mar-06, Volume: 32 Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Carcinoma, Pancreatic Ductal; Cell Growth Proce	2013
Novel agents and future prospects in the treatment of pancreatic adenocarcinoma. JOP : Journal of the pancreas, 2013, Jul-10, Volume: 14, Issue:4 Topics: Adenocarcinoma; Anilides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic	2013
High SIRT1 expression is a negative prognosticator in pancreatic ductal adenocarcinoma. BMC cancer, 2013, Oct-02, Volume: 13 Topics: Aged; Aged, 80 and over; Carcinoma, Pancreatic Ductal; Cell Cycle; Cell Line, Tumor; Cell Proliferat	2013
Pancreatic cancer: Sorafenib: no effect on efficacy of chemotherapy in pancreatic cancer. Nature reviews. Gastroenterology & hepatology, 2014, Volume: 11, Issue:1 Topics: Adenocarcinoma; Antineoplastic Agents; Cisplatin; Deoxycytidine; Drug Therapy, Combination; Gemcitab	2014
Synergistic anticancer activity of valproate combined with nicotinamide enhances anti-proliferation response and apoptosis in MIAPaca2 cells. Molecular biology reports, 2014, Volume: 41, Issue:6 Topics: Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Drug Synergism; Epigenesis, Genetic; Fl	2014
Use of sorafenib in a corticotropin-secreting pancreatic neuroendocrine carcinoma. Pancreas, 2014, Volume: 43, Issue:5 Topics: Adrenocorticotropic Hormone; Antineoplastic Agents; Carcinoma, Neuroendocrine; Humans; Male; Middle	2014
N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. Carcinogenesis, 2014, Volume: 35, Issue:10 Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Female;	2014
N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. Carcinogenesis, 2014, Volume: 35, Issue:10 Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Female;	2014
N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. Carcinogenesis, 2014, Volume: 35, Issue:10 Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Female;	2014
N-methylnicotinamide and nicotinamide N-methyltransferase are associated with microRNA-1291-altered pancreatic carcinoma cell metabolome and suppressed tumorigenesis. Carcinogenesis, 2014, Volume: 35, Issue:10 Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Female;	2014
The molecular mechanisms of a novel multi-kinase inhibitor ZLJ33 in suppressing pancreatic cancer growth. Cancer letters, 2015, Jan-28, Volume: 356, Issue:2 Pt B Topics: Animals; beta Catenin; Blotting, Western; Cell Movement; Cell Proliferation; Extracellular Signal-Re	2015
The MEK1/2 Inhibitor Pimasertib Enhances Gemcitabine Efficacy in Pancreatic Cancer Models by Altering Ribonucleotide Reductase Subunit-1 (RRM1). Clinical cancer research : an official journal of the American Association for Cancer Research, 2015, Dec-15, Volume: 21, Issue:24 Topics: Animals; Antineoplastic Agents; Apoptosis; Caspases; Cell Line, Tumor; Cell Proliferation; Cell Surv	2015
Inhibition of mutant KrasG12D-initiated murine pancreatic carcinoma growth by a dual c-Raf and soluble epoxide hydrolase inhibitor t-CUPM. Cancer letters, 2016, Feb-28, Volume: 371, Issue:2 Topics: Administration, Oral; Animals; Antineoplastic Agents; Benzoates; Carcinoma, Pancreatic Ductal; Cell	2016
Inhibition of Chronic Pancreatitis and Murine Pancreatic Intraepithelial Neoplasia by a Dual Inhibitor of c-RAF and Soluble Epoxide Hydrolase in LSL-KrasG¹²D/Pdx-1-Cre Mice. Anticancer research, 2016, Volume: 36, Issue:1 Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Carcinoma in Situ; Ceruletide; Chromatog	2016
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Sorafenib inhibits STAT3 activation to enhance TRAIL-mediated apoptosis in human pancreatic cancer cells. Molecular cancer therapeutics, 2010, Volume: 9, Issue:3 Topics: Antineoplastic Agents; Apoptosis; bcl-X Protein; Benzenesulfonates; Carcinoma; Drug Evaluation, Prec	2010
Sorafenib combined vitamin K induces apoptosis in human pancreatic cancer cell lines through RAF/MEK/ERK and c-Jun NH2-terminal kinase pathways. Journal of cellular physiology, 2010, Volume: 224, Issue:1 Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates; BH3 Interacting Domain	2010
Combined anticancer effects of sphingosine kinase inhibitors and sorafenib. Investigational new drugs, 2011, Volume: 29, Issue:6 Topics: Adamantane; Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Combined Chemotherapy Prot	2011
Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics. Cancer research, 2010, Jun-15, Volume: 70, Issue:12 Topics: Aldehyde Dehydrogenase; Aldehyde Dehydrogenase 1 Family; Animals; Antineoplastic Combined Chemothera	2010
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Synergistic cytotoxicity and molecular interaction on drug targets of sorafenib and gemcitabine in human pancreas cancer cells. Chemotherapy, 2010, Volume: 56, Issue:4 Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Benzenesulfonates;	2010
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A rare case of metastatic pancreatic hepatoid carcinoma treated with sorafenib. Journal of gastrointestinal cancer, 2012, Volume: 43, Issue:1 Topics: Adult; Antineoplastic Agents; Benzenesulfonates; Humans; Male; Neoplasm Metastasis; Niacinamide; Pan	2012
First-line treatment for advanced pancreatic cancer. Highlights from the "2011 ASCO Gastrointestinal Cancers Symposium". San Francisco, CA, USA. January 20-22, 2011. JOP : Journal of the pancreas, 2011, Mar-09, Volume: 12, Issue:2 Topics: Antineoplastic Combined Chemotherapy Protocols; Benzenesulfonates; Capecitabine; Clinical Trials as	2011
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Pancreatic endocrine tumors: a report on a patient treated with sorafenib. Journal of Korean medical science, 2011, Volume: 26, Issue:7 Topics: Adult; Antineoplastic Agents; Benzenesulfonates; Humans; Liver Neoplasms; Male; Neuroendocrine Tumor	2011
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Pancreatic metastasis arising from a BRAF(V600E)-positive papillary thyroid cancer: the role of endoscopic ultrasound-guided biopsy and response to sorafenib therapy. Thyroid : official journal of the American Thyroid Association, 2012, Volume: 22, Issue:5 Topics: Benzenesulfonates; Biopsy; Carcinoma; Carcinoma, Papillary; Disease Progression; Endoscopy; Fatal Ou	2012
Interactions of everolimus and sorafenib in pancreatic cancer cells. The AAPS journal, 2013, Volume: 15, Issue:1 Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Drug Interactions; Everolimus; Humans;	2013
Synergistic anticancer activity of HS-173, a novel PI3K inhibitor in combination with Sorafenib against pancreatic cancer cells. Cancer letters, 2013, May-01, Volume: 331, Issue:2 Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Line, Tumor; Drug Synergism; Enzy	2013
Sorafenib inhibits tumor growth and improves survival in a transgenic mouse model of pancreatic islet cell tumors. TheScientificWorldJournal, 2012, Volume: 2012 Topics: Adenoma, Islet Cell; Animals; Antigens, Polyomavirus Transforming; Apoptosis; Disease Progression; F	2012
Can sorafenib cause hypothyroidism? Journal of chemotherapy (Florence, Italy), 2007, Volume: 19, Issue:3 Topics: Antineoplastic Agents; Benzenesulfonates; Carcinoma, Islet Cell; Female; Humans; Hypothyroidism; Liv	2007
[News in digestive oncology]. Bulletin du cancer, 2008, Volume: 95, Issue:1 Topics: Antineoplastic Agents; Benzenesulfonates; Carcinoma, Hepatocellular; Cardia; Colonic Neoplasms; Comb	2008
Immunochemical identification of endocrine cell types in the streptozotocin nicotinamide-induced rat islet adenoma. Experimental and molecular pathology, 1982, Volume: 37, Issue:2 Topics: Adenoma, Islet Cell; Animals; Glucagon; Histocytochemistry; Immunochemistry; Insulin; Insulinoma; Ni	1982
Streptozotocin-induced functioning islet cell tumor in the rat: high frequency of induction and biological properties of the tumor cells. Toxicologic pathology, 1984, Volume: 12, Issue:3 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Insulin; Niacinamide; Pancreatic Neoplasms; Rats; Rats,	1984
On the histogenesis of experimental pancreatic endocrine tumors. An immunocytochemical and electron microscopical study. Acta pathologica japonica, 1984, Volume: 34, Issue:2 Topics: Adenoma; Animals; Chronic Disease; Glucagonoma; Insulinoma; Islets of Langerhans; Male; Microscopy,	1984
Modification of pancreatic carcinogenesis in the hamster model. XV. Preventive effect of nicotinamide. Journal of the National Cancer Institute, 1984, Volume: 73, Issue:3 Topics: Adenoma; Animals; Carcinogens; Carcinoma; Cricetinae; Female; Male; Mesocricetus; Niacinamide; Nitro	1984
Serially transplantable chemically induced rat islet cell tumor. Endocrinology, 1980, Volume: 107, Issue:4 Topics: Adenoma, Islet Cell; Animals; Female; Male; Neoplasm Transplantation; Neoplasms, Experimental; Niaci	1980
Pancreatic islet cell tumors found in rats given alloxan and nicotinamide. Endocrinologia japonica, 1980, Volume: 27, Issue:3 Topics: Adenoma, Islet Cell; Alloxan; Animals; Glycosuria; Islets of Langerhans; Male; Niacinamide; Pancreat	1980
Immunohistochemical and ultrastructural studies on rat islet cell tumours induced by streptozotocin and nicotinamide. Virchows Archiv. A, Pathological anatomy and histology, 1981, Volume: 390, Issue:2 Topics: Adenoma, Islet Cell; Animals; Antibodies, Neoplasm; Cell Differentiation; Male; Niacinamide; Pancrea	1981
Effect of propranolol on glucose-induced insulin response in rats with insulinomas. Endocrinologia japonica, 1980, Volume: 27, Issue:6 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Glucose; Glucose Tolerance Test; Insulin; Niacinamide;	1980
Reversal of diabetes by the isotransplantation of nicotinamide-streptozotocin-induced islet adenoma in rats. Transplantation, 1982, Volume: 33, Issue:2 Topics: Adenoma; Adenoma, Islet Cell; Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental;	1982
Poly(ADP-ribose) synthetase inhibitors enhance streptozotocin-induced killing of insulinoma cells by inhibiting the repair of DNA strand breaks. FEBS letters, 1982, Aug-23, Volume: 145, Issue:2 Topics: Adenoma, Islet Cell; Animals; Benzamides; Cell Line; Cell Survival; Cricetinae; DNA Repair; Insulino	1982
The effect of glucose on insulin and proinsulin synthesis in the streptozotocin-nicotinamide--induced rat islet adenoma. Metabolism: clinical and experimental, 1984, Volume: 33, Issue:1 Topics: Adenoma; Adenoma, Islet Cell; Animals; Electrophoresis, Polyacrylamide Gel; Glucose; Insulin; Male;	1984
The synthesis of insulin and proinsulin in a cell-free system derived from the streptozotocin-nicotinamide--induced rat islet adenoma. Metabolism: clinical and experimental, 1984, Volume: 33, Issue:1 Topics: Adenoma; Adenoma, Islet Cell; Animals; Carps; Cell-Free System; Heparin; Insulin; Liver; Male; Neopl	1984
Exocrine and endocrine secretion from isolated perfused rat pancreas with islet cell tumors induced by streptozotocin and nicotinamide. Digestive diseases and sciences, 1984, Volume: 29, Issue:5 Topics: Adenoma, Islet Cell; Animals; Culture Techniques; Glucose; Insulin; Insulin Secretion; Male; Niacina	1984
Lipid composition of glucose-stimulated pancreatic islets and insulin-secreting tumor cells. Lipids, 1994, Volume: 29, Issue:10 Topics: Adenoma, Islet Cell; Animals; Glucose; Insulin; Insulin Secretion; Islets of Langerhans; Lipids; Mic	1994
Polyarteritis nodosa-like inflammatory vascular changes in the pancreas and mesentery of rats treated with streptozotocin and nicotinamide. Journal of comparative pathology, 1997, Volume: 116, Issue:2 Topics: Adenoma, Islet Cell; Animals; Blood Vessels; Male; Mesentery; Niacinamide; Pancreas; Pancreatic Neop	1997
IFN gamma/TNF alpha synergism in MHC class II induction: effect of nicotinamide on MHC class II expression but not on islet-cell apoptosis. Diabetologia, 2002, Volume: 45, Issue:3 Topics: Animals; Apoptosis; Cell Line, Transformed; Drug Synergism; Gene Expression Regulation; Genes, MHC C	2002
[Studies on the mechanism of the diabetogenic activity of streptozotocin and on the ability of compounds to block the diabetogenic activity of streptozotocin (author's transl)]. Nihon Naibunpi Gakkai zasshi, 1975, Mar-20, Volume: 51, Issue:3 Topics: Adenoma, Islet Cell; Amides; Animals; Blood Glucose; Cats; Cystine; Deoxyglucose; Diabetes Mellitus;	1975
Proceedings: Pancreatic islet cell and other tumours induced in rats by heliotrine- a mono-ester pyrrolizidine alkaloid; the effects of additional treatment with nicotinamide. British journal of cancer, 1975, Volume: 31, Issue:2 Topics: Adenoma, Islet Cell; Animals; Neoplasms, Experimental; Niacinamide; Pancreatic Neoplasms; Pyrrolizid	1975
Experimental hypoglycemizing tumor of B-cells of Langerhans islets produced by the combined action of streptozotocin annd nicotinamide in the rat. Neoplasma, 1978, Volume: 25, Issue:2 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Female; Hypoglycemia;	1978
Tumorigenic action of streptozotocin on the pancreas and kidney in male Wistar rats. Cancer research, 1978, Volume: 38, Issue:7 Topics: Adenoma, Islet Cell; Animals; Carcinogens; Kidney Neoplasms; Liver; Male; Neoplasms, Experimental; N	1978
[Biochemical studies on rats in the course of the induction of insulin-secreting islet cell tumors by streptozotocin (author's transl)]. Nihon Naibunpi Gakkai zasshi, 1978, Nov-20, Volume: 54, Issue:11 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Carcinogens; Glucagon; Glucose Tolerance Test; Insulin;	1978
Biochemical studies on rats with insulin-secreting islet cell tumors induced by streptozotocin: with special reference to physiological response to oral glucose load in the course of and after tumor induction. Endocrinology, 1978, Volume: 103, Issue:5 Topics: Adenoma, Islet Cell; Amides; Animals; Blood Glucose; Glucose Tolerance Test; Insulin; Male; Niacinam	1978
Effect of calcium antagonist on glucose-induced insulin and glucagon secretion in rats with insulin-secreting tumors induced by streptozotocin and nicotinamide. The Kobe journal of medical sciences, 1979, Volume: 25, Issue:2 Topics: Adenoma, Islet Cell; Animals; Calcium; Diltiazem; Glucagon; Glucose; Glucose Tolerance Test; Insulin	1979
Glucagon secretion during the development of insulin-secreting tumors induced by streptozotocin and nicotinamide. Endocrinologia japonica, 1979, Volume: 26, Issue:6 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Glucagon; Glucose Tolerance Test; Insulin; Insulin Secr	1979
[Cutaneous manifestations of blind-loop syndrome]. Annales de dermatologie et de venereologie, 1990, Volume: 117, Issue:11 Topics: Blind Loop Syndrome; Diagnosis, Differential; Female; Gastrectomy; Glucagonoma; Humans; Middle Aged;	1990
Effects of pinacidil, RP 49356 and nicorandil on ATP-sensitive potassium channels in insulin-secreting cells. British journal of pharmacology, 1990, Volume: 99, Issue:3 Topics: Adenoma, Islet Cell; Adenosine Triphosphate; Diazoxide; Glucose; Guanidines; Humans; Insulin; Insuli	1990
Glucose-stimulated hormone release in rats bearing streptozotocin/nicotinamide-induced islet adenomas: evidence for slow and fast responders. Pancreas, 1989, Volume: 4, Issue:4 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Glucose; Insulin; Insulin Secretion; Male; Niacinamide;	1989
Influence of diabetes on susceptibility to experimental pancreatic cancer. American journal of surgery, 1988, Volume: 155, Issue:1 Topics: Animals; Blood Glucose; Cricetinae; Diabetes Mellitus, Experimental; Disease Susceptibility; Male; M	1988
Induction of rat pancreatic B-cell tumors by the combined administration of streptozotocin or alloxan and poly(adenosine diphosphate ribose) synthetase inhibitors. Cancer research, 1985, Volume: 45, Issue:4 Topics: Adenoma, Islet Cell; Alloxan; Amides; Animals; Insulinoma; Male; NAD+ Nucleosidase; Niacinamide; Pan	1985
Secretory, enzymatic, and morphological characterization of rat pancreatic endocrine tumours induced by streptozotocin and nicotinamide. Acta endocrinologica, 1985, Volume: 109, Issue:3 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Insulin; Insulin Secretion; Male; Niacinamide; Pancreat	1985
Morphometric analysis of the endocrine cell composition of rat pancreas following treatment with streptozotocin and nicotinamide. Experimental and molecular pathology, 1986, Volume: 44, Issue:3 Topics: Adenoma; Adenoma, Islet Cell; Animals; Blood Glucose; Glucose Tolerance Test; Insulin; Islets of Lan	1986
Chemically induced microencapsulated rat insuloma as a bioartificial endocrine pancreas. Zeitschrift fur experimentelle Chirurgie, Transplantation, und kunstliche Organe : Organ der Sektion Experimentelle Chirurgie der Gesellschaft fur Chirurgie der DDR, 1986, Volume: 19, Issue:4 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Diabetes Mellitus, Experimental; Glucose Tolerance Test	1986
Thyrotropin-releasing hormone and insulin in chemically induced pancreatic islet cell tumors in rats. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme, 1986, Volume: 18, Issue:9 Topics: Adenoma, Islet Cell; Animals; Chromatography, Gel; Insulin; Niacinamide; Pancreatic Neoplasms; Rats;	1986
On the origin of induced pancreatic islet tumors: a radioautographic study. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 1987, Volume: 184, Issue:2 Topics: Adenoma, Islet Cell; Animals; Autoradiography; DNA Replication; Male; Niacinamide; Pancreatic Neopla	1987
Pancreatic islet cell tumors produced by the combined action of streptozotocin and nicotinamide. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.), 1971, Volume: 137, Issue:1 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Carbamates; Drug Synergism; Glucosamine; Injections, In	1971
Notes on streptozotocin in metastatic insulinoma. Journal of surgical oncology, 1971, Volume: 3, Issue:5 Topics: Adenoma, Islet Cell; Adult; Antibiotics, Antineoplastic; Autopsy; Blood Glucose; Bone Marrow; Brain;	1971
[Experimental pancreatic tumor]. Nihon rinsho. Japanese journal of clinical medicine, 1972, Volume: 30, Issue:1 Topics: Adenoma, Islet Cell; Animals; Carcinogens; Cyclic N-Oxides; Dogs; Guinea Pigs; Methylation; Neoplasm	1972
Fine structure of rat islet cell tumors induced by streptozotocin and nicotinamide. Diabetologia, 1974, Volume: 10, Issue:1 Topics: Adenoma, Islet Cell; Animals; Blood Glucose; Drug Synergism; Insulin; Male; Microscopy, Electron; Ne	1974

niacinamide and Pancreatic Neoplasms

Research Excerpts

Research

Studies (99)

Authors

Clinical Trials (6)

Trial Overview

Trial Outcomes

Phase II: Overall Survival (OS) Time

Phase II: Percentage of Subjects With Clinical Benefit

Phase II: Progression-Free Survival (PFS) Time

Phase II: Time to Progression (TTP)

Safety Run-In Part: Number of Subjects With Dose Limiting Toxicities (DLTs)

Phase II: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation

Phase II: Percentage of Subjects With Best Overall Response (BOR)

Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 1

Safety Run-In Part: Apparent Oral Clearance (CL/f) of Pimasertib (MSC1936369B): Regimen 2

Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 1

Safety Run-In Part: Apparent Volume of Distribution (V) of Gemcitabine: Regimen 2

Safety Run-In Part: Area Under Curve (AUC: 0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1

Safety Run-In Part: Area Under Curve (AUC:0 to Infinity) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) Regimen 2

Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 1

Safety Run-In Part: Levels of Pharmacodynamic (Pd) Markers (Phosphorylated- Extracellular Signal-Regulated Kinase (ERK) in Peripheral Blood Mononuclear Cells [PBMCs]): Regimen 2

Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU) for Regimen 1

Safety Run-In Part: Maximum Concentration (Cmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2

Safety Run-In Part: Number of Subjects With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Permanent Treatment Discontinuation

Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 1

Safety Run-In Part: Oral Volume of Distribution (V/f) of Pimasertib (MSC1936369B): Regimen 2

Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1

Safety Run-In Part: Time to Reach Apparent Terminal Half-Life (t1/2) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2

Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 1

Safety Run-In Part: Time to Reach Maximum Concentration (Tmax) of Pimasertib (MSC1936369B), Gemcitabine (dFdC), and Gemcitabine Inactive Metabolite 2',2'-Difluorodeoxyuridine (dFdU): Regimen 2

Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 1

Safety Run-In Part: Total Clearance (CL) of Gemcitabine: Regimen 2

The Median Progression Free Survival Time Will be Determined.

The Median Survival Time Will be Determined.

One- and Two-year Overall Survival Rate Will be Determined.

One- and Two-year Progression Survival Rate Will be Determined. Will be Determined.

The Quality of Life Will be Analyzed.

Treatment-related Adverse Effects Will be Determined.

Reviews

Trials

Other Studies