598TiP - PRODIGE 86 (FFCD 2103 - GONO) – FOLFIRINOX SBA: Phase II randomized trial to evaluate mFOLFIRINOX and mFOLFOX in the treatment of locally advanced or metastatic small bowel adenocarcinoma

Background

Small bowel adenocarcinoma (SBA) is rare. Palliative chemotherapy was evaluated mainly in retrospective studies and the fluoropyrimidine + oxaliplatin combination regimen appears to be the most efficient. No randomized trial has been previously performed to evaluate front line chemotherapy in advanced SBA.

Trial design

Randomized, non-comparative, open-label, multi-centre phase II study to evaluate mFOLFIRINOX and mFOLFOX in the treatment of locally advanced or metastatic SBA. Randomization (1:1) of patients will be stratified according to: centre, locally advanced tumour vs synchrous metastases vs metachronous metastases, performance status ECOG 0-1 vs 2. Study objectives: Primary: to assess the percentage of patients alive without progression at 8 months. Secondary: overall survival, progression-free survival (PFS), time to treatment failure, tumor response during rate, tolerance, quality of life, PFS in 2nd line. The hypothesis are: H0: <40% of patients alive without progression at 8 months is insufficient, a rate of 55% is expected. Alpha=10% (one-sided), power=85%. 65 patients per arm will be randomized. Treatment: mFOLFOX regimen D1=D15: oxaliplatin 85 mg/m2, folinic acid: 400 mg/m2, 5FU bolus: 400 mg/m2 followed by 5FU: 2400 mg/m2 IV infusion over 46 hours. mFOLFIRINOX regimen same as mFOLFOX plus irinotecan 180 mg/m2, without 5FU bolus Patients will receive treatment until progression, patient refusal or unacceptable toxicity. Mains inclusion criteria: histologically proven adenocarcinoma of the SBA, metastatic or locally advanced unresectable tumour, no first-line chemotherapy, measurable lesion according to RECIST 1.1, ECOG status <2 (0 or 1 for patients >70 years), life expectancy estimated >3 months, patient >18 years. Main exclusion criteria: MSI/dMMR tumor, adenocarcinoma of the ampulla of Vater, abnormal biology, adjuvant chemotherapy completed <6 months ago, recent severe cardiovascular co-morbidity, significant peripheral sensory neuropathy, active and/or potentially severe infection or other uncontrolled conditions. The randomization has started in April 2024.

Clinical trial identification

EU clinical trial registry number: 2023-505486-92.

Editorial acknowledgement

Legal entity responsible for the study

Fédération Francophone de Cancérologie Digestive.

Funding

Programme Hospitalier de Recherche Clinique, INCA.

Disclosure

T. Aparicio: Financial Interests, Personal, Invited Speaker, 2022: Servier; Financial Interests, Personal, Invited Speaker, 3 Conferences: Pierre Fabre; Financial Interests, Personal, Advisory Board, 2 Board in 2022 and 2023: BMS; Financial Interests, Personal, Invited Speaker, 1 conference: MSD; Non-Financial Interests, Leadership Role, 2021-2024: Fédération Francophone de Cancérologie Digestive. All other authors have declared no conflicts of interest.