FOLFIRINOX-R study design: a phase I/II trial of FOLFIRINOX plus regorafenib as first line therapy in patients with unresectable RAS-mutated metastatic colorectal cancer

BMC Cancer

Julien Fraisse¹  Stéphanie Delaine²  Patrick Chalbos²  Ludovic Evesque³  Francois Ghiringhelli⁴  Caroline Mollevi⁵  Thibault Mazard⁶  Marc Ychou⁶  Antoine Adenis⁷  Brice Pastor⁸ 

[1] Biometrics Unit, Montpellier Cancer Institute (ICM), Montpellier, France;Department of Clinical Research, Montpellier Cancer Institute (ICM), University of Montpellier, Montpellier, France;Department of Medical Oncology, Centre Antoine Lacassagne, Nice, France;Department of Medical Oncology, Georges François Leclerc, Dijon, France;IRCM, Inserm, Université Montpellier, ICM, Montpellier, France;Biometrics Unit, Montpellier Cancer Institute (ICM), Montpellier, France;IRCM, Inserm, Université Montpellier, ICM, Montpellier, France;Department of Medical Oncology, Montpellier Cancer Institute (ICM), Montpellier, France;IRCM, Inserm, Université Montpellier, ICM, Montpellier, France;Department of Medical Oncology, Montpellier Cancer Institute (ICM), Montpellier, France;Department of Gastrointestinal Oncology, Institut Régional du Cancer de Montpellier, 208 Avenue des Apothicaires, 34000, Montpellier, France;IRCM, Inserm, Université Montpellier, ICM, Montpellier, France;IRCM, Inserm U1194, Montpellier, France;

关键词: Colorectal cancer;    Chemotherapy triplet;    Regorafenib;    Phase 1–2 trial;   

DOI  :  10.1186/s12885-021-08312-7

来源: Springer

【 摘 要 】

BackgroundThe chemotherapy triplet FOLFOXIRI combined to the anti-VEGF antibody bevacizumab is an option in selected patients with metastatic colorectal cancer. In this setting, RAS-mutated metastatic colorectal cancer do not benefit the same from treatment than RAS-wildtype metastatic colorectal cancer do. Together with its antiangiogenic properties, the tyrosine-kinase inhibitor regorafenib has also anti-proliferative activities whatever the RAS status is. The present trial aims at studying the safety and the efficacy of regorafenib in combination with FOLFIRINOX – a chemotherapy triplet using a different dosing schedule than FOLFOXIRI - in patients with RAS-mutated metastatic colorectal cancer.MethodsFOLFIRINOX-R is a prospective, multicentric, non-randomised, dose-finding phase 1–2 trial. The primary endpoints are the determination of the maximum tolerated dose, the recommended phase 2 dose, and the proportion of patients achieving disease control at 48-weeks. Phase 1 follows a 3 + 3 design (12 to 24 patients to be included). Sixty nine patients will be necessary in phase 2, including 5% non-evaluable ones, with the following assumptions, one-stage Fleming design, α = 5%, β = 20%, p0 = 35% and p1 = 50%. Key eligibility criteria include Eastern Cooperative Oncology Group Performance Status of ≤1 and RAS-mutated metastatic colorectal cancer not amenable to surgery with curative intent and not previously treated for metastatic disease. FOLFIRINOX (oxaliplatin 85 mg/m2, folinic acid 400 mg/m2, irinotecan 150–180 mg/m2, 5-fluorouracil: 400 mg/m2 then 2400 mg/m2 over 46 h) is administered every 14 days. Regorafenib (80 to 160 mg, as per dose-level) is administered orally, once daily on days 4 to 10 of each cycle.DiscussionFOLFIRINOX-R is the first phase I/II study to evaluate the safety and efficacy of regorafenib in combination with FOLFIRINOX as frontline therapy for patients with RAS-mutated metastatic colorectal cancer.Trial registrationEudraCT: 2018-003541-42; ClinicalTrials.gov: NCT03828799.

【 授权许可】

CC BY