Adjuvant FOLFIRI after surgery for colorectal liver metastases that responded to preoperative FOLFIRI
"Interest of Postoperative Reintroduction of Chemotherapy in Patients Undergoing Resection of Colorectal Liver Metastases After Good Response to FOLFIRI-based Chemotherapy With or Without Targeted Agent" (Intergroup FRENCH- PRODIGE)
This trial tests whether giving FOLFIRI chemotherapy after liver surgery helps people whose colorectal liver metastases responded to preoperative FOLFIRI and who could not receive oxaliplatin.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 254 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Paris, Île-de-France Region) |
| Trial ID | NCT06501482 on ClinicalTrials.gov |
What this trial studies
This is a national, multicenter, open-label, randomized phase III trial comparing postoperative reintroduction of FOLFIRI-based chemotherapy versus no postoperative treatment in patients who had resection of colorectal liver metastases after responding to preoperative FOLFIRI (with or without targeted agents). Eligible patients have metachronous liver-only disease (≤10 metastases), received 2–8 cycles of preoperative FOLFIRI, achieved an objective radiologic or pathologic response, and had curative-intent R0/R1 resection within 12 weeks of chemotherapy. Patients are randomized to receive adjuvant FOLFIRI or observation, and the primary endpoint is 3-year disease-free survival. The trial is sponsored by Assistance Publique - Hôpitaux de Paris and conducted at participating centers in France, with Hôpital Kremlin Bicêtre listed as a lead site.
Who should consider this trial
Good fit: Patients with metachronous, resected colorectal liver metastases (≤10 lesions) who showed a radiologic or major pathologic response to preoperative FOLFIRI and who could not receive oxaliplatin are the ideal candidates.
Not a fit: Patients with extrahepatic disease, lack of objective response to preoperative FOLFIRI, or those who already received perioperative oxaliplatin-based chemotherapy are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, reintroducing FOLFIRI after surgery could reduce recurrence and increase disease-free survival for this selected group of patients.
How similar studies have performed: Perioperative oxaliplatin-based chemotherapy has shown benefit in resectable colorectal liver metastases, but postoperative reintroduction of FOLFIRI in this specific subgroup (oxaliplatin-contraindicated, good responders) has limited prior evidence.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Histologically proven resected metachronous CLM with curative intent that could not be treated with perioperative oxaliplatin-based chemotherapy for oncologic or tolerability reasons. For this study, metachronous CLM is defined as liver recurrence occurring more than 12 months after treatment of the primary colorectal cancer. * No more than 10 treated CLM at surgery * At least 2 cycles and no more than 8 cycles of preoperative FOLFIRI based chemotherapy ± targeted therapy. * Preoperative FOLFIRI based chemotherapy ± targeted therapy administered no more than 12 weeks before surgery * R0/R1resection ± radiofrequency ablation with curative intent of all liver deposits with no macroscopic residual liver disease * Objective response to preoperative therapy defined as complete or partial radiological response and/or major or complete pathologic response * No extrahepatic or residual liver disease on baseline work-up including thoraco-abdominal CT scan within 6 weeks after surgery. 1 non-specific lung nodule of less than 10 mm in maximum diameter is not considered as extra-hepatic metastases * Primary tumor (or liver metastasis) of CRC must be characterized for RAS and BRAF status * No contraindication to FOLFIRI based chemotherapy * Patients must be 18 years old or older * A WHO performance status of 0 or 1 * Participants must be affiliated to a social security scheme Exclusion Criteria: * Palliative/R2 resection of CLM * 10 lesions or more treated at the time of surgery * Patients undergoing only radiofrequency ablation of all liver deposit (this situation precludes the assessment of pathologic response to preoperative chemotherapy) * Extra-hepatic or residual metastasis of CRC * Absence of objective response to therapy (radiological or pathological response ) * Inflammatory bowel disease * Known UGT1A1\*28 allele homozygosity * complete absence of dihydropyrimidine dehydrogenase (DPD) activity (blood uracil level ≥ 150 ng/ml * Contraindications to investigational medicinal products (irinotecan, 5-FU, folinic acid) and to auxiliary medicinal products (ondansetron, methylprednisolone) * Persistent toxicity ≥ grade 1 related to preoperative FOLFIRI based chemotherapy * Known pregnancy (pregnancy test for women of childbearing) or breastfeeding women
Where this trial is running
Paris, Île-de-France Region
- Hôpital Kremlin Bicêtre — Paris, Île-de-France Region, France (Recruiting)
Study contacts
- Principal investigator: Eric VICAUT, MHD, PHD — Aphp
- Study coordinator: Stéphane BENOIST, MHD, PHD
- Email: Stephane.benoist@aphp.fr
- Phone: 33 1 45 21 34 72
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.