RecruitingPhase 3NCT06501482

Adjuvant FOLFIRI Based-chemotherapy After Resection of CLM Responding 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)

Sponsor

Assistance Publique - Hôpitaux de Paris

Enrollment

254 participants

Start Date

Jun 27, 2025

Study Type

INTERVENTIONAL

Conditions

Colorectal, Cancer Colorectal Liver Metastases

Summary

Eligible patients are patients with contraindication to preoperative oxaliplatin based-chemotherapy who underwent resection of no more than 10 colorectal liver metastases after preoperative FOLFIRI based chemotherapy with or without targeted agents. These patients must have objective response to treatment (radiologic or pathologic response). The standard care for these patients is no postoperative treatment although benefit of reintroduction of FOLFIRI chemotherapy in good responders could be expected. This study is a National, multicenter, open-label randomized, 2-arm, phase III superiority trial comparing postoperative reintroduction of FOLFIRI based-chemotherapy (experimental arm) vs no treatment (control arm) in patients undergoing resection of colorectal liver metastases after good response to FOLFIRI-based chemotherapy with or without targeted agent. The primary endpoint of the study is 3-year disease free survival. Based on published data, 3-year DFS in control group (absence of postoperative treatment is 25%. Expected 3-year DFS in the experimental group is 40%. The study will randomize 254 patients (127 in the chemotherapy group and 127 in the no treatment group) in 30 french academic centers.

Eligibility

Min Age: 18 Years

Inclusion Criteria12

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 Criteria11

Palliative/R2 resection of CLM
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

Interventions

DRUGPostoperative reintroduction of FOLFIRI based chemotherapy

Postoperative reintroduction of FOLFIRI: irinotecan 180 mg/m2 + leucovorin 400 mg/m2 at day 1 then 5-FU 400 mg/m2 bolus followed by 2400 mg/m2 continuous infusion over 46 h biweekly. For a total of 12 cycles of perioperative chemotherapy including the preoperative chemotherapy