FOLFIRINEC: a randomized phase II trial of mFOLFIRINOX vs platinum-etoposide for metastatic neuroendocrine carcinoma of gastroenteropancreatic or unknown origin

Dig Liver Dis. 2021 Jul;53(7):824-829. doi: 10.1016/j.dld.2021.04.016. Epub 2021 May 12.

Abstract

Background: Poorly differentiated neuroendocrine carcinomas (NEC) are rare diseases with a poor prognosis. Platinum-etoposide (PE) has been the recommended first-line treatment for decades. FOLFIRINEC (NCT04325425) is a national multicenter randomized phase II study which aims to challenge this standard regimen.

Methods: The primary objective is to compare the median progression-free survival (PFS) under mFOLFIRINOX versus PE. The secondary objectives are to evaluate the objective response rates (ORR), median overall survival (OS), safety and quality of life. The associated real-time translational study will establish a molecular profile for each patient enrolled.

Main inclusion criteria are: NEC of gastroenteropancreatic (GEP) or unknown origin, metastatic and RECIST 1.1 evaluable disease, tumor sample available and no contraindication to chemotherapy. Patients will be randomized 1:1 between PE every 21 days for 6-8 cycles and mFOLFIRINOX every 14 days for up to 12 cycles and stratified according to center, performance status, Ki67 and pathological subtype. This trial will randomize 218 patients (24 months of follow-up) to have 80% power to detect an improvement of the median PFS from 5 months under PE to 7.5 months under mFOLFIRINOX (HR of 0.67, α =5%, two-sided). An intermediate analysis is planned at 50% of events. Recruitment started on October 20, 2020.

Keywords: Chemotherapy; FOLFIRINOX; Gastroenteropancreatic; Neuroendocrine carcinoma.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Biomarkers / analysis
  • Carcinoma, Neuroendocrine / drug therapy*
  • Etoposide / administration & dosage*
  • Female
  • Fluorouracil / administration & dosage
  • Humans
  • Intestinal Neoplasms / drug therapy*
  • Irinotecan / administration & dosage
  • Leucovorin / administration & dosage
  • Male
  • Neoplasm Metastasis
  • Neoplasms, Unknown Primary / drug therapy*
  • Neuroendocrine Tumors / drug therapy*
  • Oxaliplatin / administration & dosage
  • Pancreatic Neoplasms / drug therapy*
  • Platinum Compounds / administration & dosage*
  • Progression-Free Survival
  • Prospective Studies
  • Quality of Life
  • Stomach Neoplasms / drug therapy*
  • Survival Rate
  • Treatment Outcome

Substances

  • Biomarkers
  • Platinum Compounds
  • folfirinox
  • Oxaliplatin
  • Etoposide
  • Irinotecan
  • Leucovorin
  • Fluorouracil

Supplementary concepts

  • Gastro-enteropancreatic neuroendocrine tumor