Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer
Van C. E., Hidalgo M., Canon J. -., Macarulla T., Bazin I., Poddubskaya E. V., Manojlovic N., Radenkovic D., Verslype C., Raymond E., Cubillo A., Schueler A., Zhao C., Hammel P.
International Journal of Cancer
Vol.143, Issue8, P. 2053-2064
Опубликовано: 2018
Тип ресурса: Статья
Аннотация:
The selective MEK1/2 inhibitor pimasertib has shown anti-tumour activity in a pancreatic tumour model. This phase I/II, two-part trial was conducted in patients with metastatic pancreatic adenocarcinoma (mPaCa) (NCT01016483). In the phase I part, oral pimasertib was given once daily discontinuously (5 days on/2 days off treatment) or twice daily continuously (n = 53) combined with weekly gemcitabine (1,000 mg/m2) in 28-day cycles to identify the recommended phase II dose (RP2D) of pimasertib. In the phase II part, patients were randomised to pimasertib (RP2D) or placebo plus weekly gemcitabine (n = 88) to investigate progression-free survival (PFS), overall survival (OS) and safety. The RP2D was determined to be 60 mg BID. PFS and OS outcomes did not indicate any treatment benefit for pimasertib over placebo in combination with gemcitabine (median PFS 3.7 and 2.8 months, respectively, HR = 0.91, 95[%] CI: 0.58–1.42: median OS 7.3 vs. 7.6 months, respectively). KRAS status did not influen
Ключевые слова:
KRAS; MEK; metastatic; pancreatic cancer; pimasertib; randomised controlled trial
gemcitabine; pimasertib; placebo; antineoplastic agent; deoxycytidine; gemcitabine; N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide; nicotinamide; abdominal pain; adult; aged; anemia; Article; asthenia; bleeding; cancer survival; central serous retinopathy; diarrhea; disorientation; drug half life; fatigue; febrile neutropenia; female; fever; human; incidence; loss of appetite; major clinical study; male; multiple cycle treatment; nausea; neutropenia; overall survival; pancreas metastasis; patient safety; peripheral edema; phase 1 clinical trial; phase 2 clinical trial; priority journal; progression free survival; randomized controlled trial; rash; retina detachment; stomatitis; suicidal ideation; thrombocytopenia; time to maximum plasma concentration; vomiting; adenocarcinoma; analogs and derivatives; clinical trial; middle aged; pancreas tumor; very elderly; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deoxycy
Язык текста: Английский
ISSN: 1097-0215
Van C. E. Cutsem E.
Hidalgo M.
Canon J. -. J.-L.
Macarulla T.
Bazin I.
Poddubskaya E. V. Elena Vladimirovna 1965-
Manojlovic N.
Radenkovic D.
Verslype C.
Raymond E.
Cubillo A.
Schueler A.
Zhao C.
Hammel P.
Ван C. Е. Cуцем Е.
Хидалго М.
Cанон Й. -. Й.-Л.
Маcарулла Т.
Базин И.
Поддубская Е. В. Елена Владимировна 1965-
Манойловиc Н.
Раденковиc Д.
Верслyпе C.
Раймонд Е.
Cубилло А.
Счуелер А.
Жао C.
Хаммел П.
Phase I/II trial of pimasertib plus gemcitabine in patients with metastatic pancreatic cancer
Текст визуальный непосредственный
International Journal of Cancer
John Wiley & Sons
Vol.143, Issue8 P. 2053-2064
2018
Статья
KRAS MEK metastatic pancreatic cancer pimasertib randomised controlled trial
gemcitabine pimasertib placebo antineoplastic agent deoxycytidine gemcitabine N-(2,3-dihydroxypropyl)-1-((2-fluoro-4-iodophenyl)amino)isonicotinamide nicotinamide abdominal pain adult aged anemia Article asthenia bleeding cancer survival central serous retinopathy diarrhea disorientation drug half life fatigue febrile neutropenia female fever human incidence loss of appetite major clinical study male multiple cycle treatment nausea neutropenia overall survival pancreas metastasis patient safety peripheral edema phase 1 clinical trial phase 2 clinical trial priority journal progression free survival randomized controlled trial rash retina detachment stomatitis suicidal ideation thrombocytopenia time to maximum plasma concentration vomiting adenocarcinoma analogs and derivatives clinical trial middle aged pancreas tumor very elderly Adenocarcinoma Adult Aged Aged, 80 and over Antineoplastic Combined Chemotherapy Protocols Deoxycy
The selective MEK1/2 inhibitor pimasertib has shown anti-tumour activity in a pancreatic tumour model. This phase I/II, two-part trial was conducted in patients with metastatic pancreatic adenocarcinoma (mPaCa) (NCT01016483). In the phase I part, oral pimasertib was given once daily discontinuously (5 days on/2 days off treatment) or twice daily continuously (n = 53) combined with weekly gemcitabine (1,000 mg/m2) in 28-day cycles to identify the recommended phase II dose (RP2D) of pimasertib. In the phase II part, patients were randomised to pimasertib (RP2D) or placebo plus weekly gemcitabine (n = 88) to investigate progression-free survival (PFS), overall survival (OS) and safety. The RP2D was determined to be 60 mg BID. PFS and OS outcomes did not indicate any treatment benefit for pimasertib over placebo in combination with gemcitabine (median PFS 3.7 and 2.8 months, respectively, HR = 0.91, 95[%] CI: 0.58–1.42: median OS 7.3 vs. 7.6 months, respectively). KRAS status did not influen