PRODIGE 86

PRODIGE 86 (FFCD 2103) – FOLFIRINOX SBA is an European study in which GONO is participating as part of the international collaboration with FFCD – UNICANCER GI – GERCOR- ENGIC (European Network In GastroIntestinal Cancer).
The study is sponsored by the French group CHU Dijon Bourgogne and will be conducted in France and Italy.

Small bowel adenocarcinoma (SBA) is a rare disease, accounting for less than 5% of all gastrointestinal tumours.
Adenocarcinoma of the duodenum is the most common tumour site, occurring in more than half of all SBA cases, followed by the jejunum and ileum. An increasing incidence of SBA is reported, mainly due to the increase in duodenal tumours. At the time of diagnosis, approximately 40% of patients have distant metastases and more than half of patients with resected tumours and lymph node involvement will have a metastatic recurrence.
Characterisation of the tumour phenotype indicates that the molecular alterations of SBA are more similar to colorectal adenocarcinoma. Recent genomic profiling studies of SBA report a significant proportion of tumours with relevant targets.
Fluoropyrimidine + platinum salts and especially oxaliplatin appear to be the most effective compared to other regimens.
Two prospective phase II studies evaluated oxaliplatin in combination with 5FU or capecitabine and reported an ORR of approximately 50%, median PFS of 7.8 and 11.3 months, median OS of 15.2 and 20.4 months. Indeed, FOLFOX (5FU IV + oxaliplatin) is the most frequently used first-line chemotherapy in France. Treatment with an anti-EGFR monoclonal antibody has been evaluated in a pilot study which reported no efficacy signals. Bevacizumab has also been evaluated in a phase II study in combination with capecitabine and oxaliplatin with results comparable to those observed in a previous phase II study with the same chemotherapy regimen, but without bevacizumab. Furthermore, a registry study suggests no benefit of adding bevacizumab to chemotherapy for SBA. It therefore appears that FOLFOX or CAPOX (capecitabine + oxaliplatin), without targeted therapy, are the best options for first-line treatment of metastatic SBA and are the recommended treatment in France.
In metastatic colorectal adenocarcinoma, the triplet 5FU + oxaliplatin + irinotecan showed better efficacy than FOLFIRI. The superiority of triplet chemotherapy observed in metastatic colorectal adenocarcinoma and pancreatic adenocarcinoma argues for evaluation in metastatic SBA.
Due to the rarity of the disease, a phase III trial is not feasible with a reasonable duration. A first step will be a randomized phase II trial to validate the efficacy signal of triplet chemotherapy.

– Histologically proven adenocarcinoma of the small intestine (duodenum, jejunum, ileum)
– Metastatic or locally advanced unresectable tumour with curative intent
– Patient who never received first-line chemotherapy
– ECOG status < or = 2 for patients under 70 years, or 0 or 1 for patients over 70 years

Primary objective: To assess the percentage of patients alive without progression at 8 months.

Secondary objectives:
– Overall survival
– Progression-free survival (PFS)
– Time to treatment failure (TTF)
– Better response during first line treatment
– Treatment tolerance according to NCI-CTC 4.0
– Quality of life during treatment (QLQ-C30)
– PFS in 2nd line of the total population and by 2nd line treatment