PRODIGE 98 -FFCD 2105 - AMPIRINOX

To assess efficacy of adjuvant mFOLFIRINOX versus single-agent chemotherapy (gemcitabine or capecitabine) in improving disease-free survival (DFS) after surgical resection of an ampullary adenocarcinoma.

1. Overall survival (OS).
2. Rate of patients completing 3 and 6-month chemotherapy schedule according to percentage of administered dose of each product.
3. Assessment of quality of life by EORTC QLQ-C30 and QLQ-PAN26.
4. Assessment of toxicities according to NCI-CTCAE v5.0.
5. Subgoup analyses on OS and DFS by prespecified subgroups.

1. Histologically proven adenocarcinoma on surgical specimen.
2. Macroscopically complete surgical resection of an ampullary adenocarcinoma (R0 or R1).
3. Adenocarcinoma removed within 12 weeks prior to enrollment.
4. Patients ≥ 18 years of age.
5. Patient without metastatic disease on CT scan < 4 weeks prior to inclusion.
6. WHO performance status 0 or 1 (WHO 0 if age >75).
7. Normal values of kalemia, magnesemia and calcemia.
8. Patient able to understand and sign the information and informed consent note.
9. Women of childbearing age and men who are sexually active with women of childbearing age must agree to use highly effective contraception during the trial treatment at least until 6 months after the end of the experimental treatment. Women of childbearing potential must use highly effective contraception at least until 9 months after the end of the treatment with oxaliplatin.
10. Patient affiliated to a social security scheme for France, or equivalents in European countries.
11. CA19.9 level < 180 U/L at inclusion (post-operative level).

1. Neoadjuvant systemic chemotherapy.
2. pT1N0M0 tumors.
3. Active infection by HBV, HCV or HIV.
4. Dihydropyrimidine dehydrogenase deficiency (uracilemia ≥ 16 ng/mL).
5. Pre-existing peripheral neuropathy (grade ≥ 2).
6. Unresolved or uncontrolled concomitant medical conditions.
7. Neutrophils < 1500/mm³, platelets < 150 000/mm³, Haemoglobin < 9 g/dL.
8. Total bilirubin > 1.5 x normal.
9. Creatinine clearance < 50 ml/min according to MDRD.
10. AST or ALT > 2.5 x UNL, alkaline phosphatase > 2.5 x normal at least 15 days after resection.
11. Patients with poor nutritional status represented by albuminemia < 30.0g/dl.
12. History of myocardial infarction within the last 6 months, severe coronary artery disease or severe heart failure.
13. Active and/or potentially severe infection.
14. Treatment with a strong cytochrome P450 inhibitor within 4 weeks prior to the administration of the protocol treatment (Treatment with Hypericum perforatum).
15. Patient under treatment by brivudine, or treated by brivudine within 4 weeks prior to beginning of study treatment.
16. Concomitant use with St John’s Wort.
17. QT/QTc interval longer than 450msec for men and longer than 470msec for women on the ECG.
18. Hypersensitivity to any of the study products or their excipients.
19. Administration of live vaccines within 28 days prior to randomization.
20. Other cancer treated within the last 5 years except adequately treated, in situ cervical carcinoma or basocellular/spinocellular carcinoma.
21. Chronic bowel disease requiring specific treatment and/or intestinal obstruction.
22. Pregnant or breastfeeding woman.
23. Person under guardianship.
24. Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons.

Lancement de l’étude : Mai 2025
Fin estimée des inclusions : Mai 2029
Nombre de patients à inclure : 292

Dr Gaël ROTH – CHU de Grenoble

Fédération Francophone de Cancérologie Digestive (FFCD)