PRODIGE 98 : Randomized, Multicenter Phase 3 Trial of Adjuvant Chemotherapy With Modified FOLFIRINOX Versus Capecitabine or Gemcitabine in Patients With Resected Ampullary Adenocarcinoma

NCT06813976 | Recruiting Phase 3

• 1 other identifier: MANFREDI PHRCK 2023
• Study Type: interventional
• Target: 294
• Locations: 1 country
• Sites: 1

Brief Summary

Ampullary adenocarcinoma (AMPAC) is a rare cancer (0.2% of digestive cancers) affecting the ampulla of Vater. The only curative treatment is surgery, but around 4% of patients recur within 2 years of surgical resection. The aim of adjuvant chemotherapy is to reduce the risk of disease recurrence, and the only chemotherapies that can be considered standard to date are capecitabine and gemcitabine. In this trial, an alternative experimental treatment strategy using modified FOLFORINOX (mFOLFORINOX) is proposed. It consists of 3 chemotherapies with complementary actions: 5-fluorouracil, irinotecan and oxaliplatin, combined with folic acid a vitamin that enhances the efficacy of 5-fluorouracil. This study proposes 2 treatment schemes:

• Group A: mFOLFIRINOX: oxaliplatin, irinotecan, 5-fluorouracil, with folinic acid,
• group B: mono-chemotherapy with capecitabine or gemcitabine.

Conditions

Ampullary Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Disease-free survival (DFS)

  To compare DFS between the 2 arms of treatments in randomized patients

  Assessed up to 36 months

Study Arms (2)

Experimental strategy

EXPERIMENTAL

Drug: mFOLFORINOX; Other: Quality of life questionnaires: QLQ-C30 and PAN26; Biological: Biological assessment; Diagnostic Test: Paraclinical examinations

Standard treatments

ACTIVE COMPARATOR

Drug: Capecitabine or gemcitabine; Other: Quality of life questionnaires: QLQ-C30 and PAN26; Biological: Biological assessment; Diagnostic Test: Paraclinical examinations

Interventions

mFOLFORINOX DRUG

mFOLFIRINOX every 2 weeks during 12 cycles (24 weeks): * Oxaliplatin 85 mg/m² * Irinotecan 150 mg/m² * Leucovorin 400 mg/m² * Fluorouracil 2400 mg/m² during 46 hours

Experimental strategy

Capecitabine or gemcitabine DRUG

investigator's choice: * Capecitabine 1250 mg/m² BID, 2 weeks on, 1 week off during 8 cycles (24 weeks) OR * Gemcitabine 1000 mg/m² in 30 min; 3 weeks on, 1 week of, during 6 cycles ((24 weeks)

Standard treatments

Quality of life questionnaires: QLQ-C30 and PAN26 OTHER

Before treatment, during treatment (every 12 weeks in any treatment arm Until disease progression or end of follow-up) and after treatment discontinuation (30 days after the end of treatment)

Experimental strategy; Standard treatments

Biological assessment BIOLOGICAL

Before each course of treatment and between courses of treatment if necessary

Experimental strategy; Standard treatments

Paraclinical examinations DIAGNOSTIC_TEST

Every 3 months

Experimental strategy; Standard treatments

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven adenocarcinoma on surgical specimen
• Macroscopically complete surgical resection of an ampullary adenocarcinoma (R0 or R1)
• Adenocarcinoma removed within 12 weeks prior to enrollment
• Patients ≥ 18 years of age
• WHO performance status 0 or 1 (WHO 0 if age \>75)
• Normal values of kalemia, magnesemia and calcemiaPatient able to understand and sign the information and informed consent note
• 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 experimental treatment. Women of childbearing potential must use highly effective contraception at least 9 months after the end of treatment with oxaliplatin
• Patient affiliated to a social security scheme for France, or equivalents in European countries

You may not qualify if:

• Neoadjuvant systemic chemotherapy
• pT1N0M0 tumors
• Active infection by HBV, HCV or HIV
• Dihydropyrimidine dehydrogenase deficiency (uracilemia ≥ 16 ng/mL)
• Pre-existing peripheral neuropathy (grade ≥ 2)
• Unresolved or uncontrolled concomitant medical conditions
• Neutrophils \< 1500/mm3, platelets \< 150 000/mm3, Haemoglobin \< 9 g/dL
• Total bilirubin \> 1.5x normal,
• Creatinine clearance \< 50 ml/min according to MDRD
• AST or ALT \> 2.5 x UNL, alkaline phosphatase \> 2.5x normal at least 15 days after resection
• Patients with poor nutritional status represented by albuminemia \< 30.0g/dl
• History of myocardial infarction within the last 6 months, severe coronary artery disease or severe heart failure
• Active and/or potentially severe infection
• Treatment with a strong cytochrome P450 inhibitor within 4 weeks prior to the administration of the protocol treatment (Treatment with Hypericum perforatum)
• Patient under treatment by brivudine, or treated by brivudine within 4 weeks prior to beginning of study treatment

Sponsors & Collaborators

• Centre Hospitalier Universitaire Dijon: lead

Study Sites (1)

CHU Dijon Bourgogne

Dijon, 21000, France

RECRUITING

MeSH Terms

Interventions

Capecitabine; Gemcitabine

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Central Study Contacts

Gaël ROTH

CONTACT

04 76 76 51 68; groth@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: February 7, 2025
• Study Start: July 2, 2025
• Primary Completion (Estimated): July 1, 2033
• Study Completion (Estimated): July 1, 2033
• Last Updated: July 11, 2025

Record last verified: 2025-07

Locations

FR (1)