Adjuvant FOLFIRI Based-chemotherapy After Resection of CLM Responding to Preoperative FOLFIRI

NCT06501482 | Recruiting Phase 3

• 2 other identifiers: 2209172023-504831-42-00
• Study Type: interventional
• Target: 254
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Colorectal Cancer; Colorectal Liver Metastases

Keywords

Resected colorectal liver metastases; Response to preoperative chemotherapy; Postoperative FOLFIRI based chemotherapy; Disease-free survival

Outcome Measures

Primary Outcomes (1)

• The disease-free survival rate

  Disease-free survival rate at 3 years defined as the proportion of surviving patients without disease recurrence measured by Kaplan-Meier in the two treatment arms from the time to randomization. Disease-free survival will be defined as follows: time between randomization and disease recurrence or death whichever occurs first. In this trial, the disease-free survival is defined as the time to occurrence of first recurrence or death whatever comes first. Diagnosis of recurrence can be made only when the clinical and laboratory findings meet at least one of the criteria defined below: * Objective radiological recurrence on radiological imaging (ultrasound, CT scan, MRI scan, TEP scan as indicated by the clinical picture) * Positive cytology or biopsy (in case of ascites, anastomotic recurrence, doubt on radiological imaging) Note: an isolated elevated tumor marker level will not be considered acceptable evidence of cancer recurrence. * Death.

  3 years

Secondary Outcomes (2)

• The overall survival rate

  3 years

• The Liver-free survival rate

  3 years

Other Outcomes (5)

• The Extra -hepatic recurrence rate

  3 years

• The safety including chemotherapy associated toxicity assessed by International Common Terminology Criteria for Adverse Events (CTCAE) grading system

  At each cycle of postoperative FOLFIRI chemotherapy administration for a total of 12 cycles perioperative (including the preoperative chemotherapy) and each cycle is 15 days, then every 3 months for 2 years and then every 6 months for 3 years

• The compliance

  At each cycle of postoperative FOLFIRI chemotherapy administration for a total of 12 cycles perioperative (including the preoperative chemotherapy) and each cycle is 15 days

Study Arms (2)

Postoperative FOLFIRI group

EXPERIMENTAL

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

Drug: Postoperative reintroduction of FOLFIRI based chemotherapy

No treatment group (control group)

NO INTERVENTION

No treatment

Interventions

Postoperative reintroduction of FOLFIRI based chemotherapy DRUG

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

Postoperative FOLFIRI group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Hôpital Kremlin Bicêtre

Paris, Île-de-France Region, 75010, France

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Eric VICAUT, MHD, PHD

  APHP

  STUDY CHAIR

• Eric VICAUT, MHD, PHD

  APHP

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Stéphane BENOIST, MHD, PHD

CONTACT

33 1 45 21 34 72; Stephane.benoist@aphp.fr

Antoine BROUQUET, MHD, PHD

CONTACT

+33 1 45 21 34 70; Anoine.brouquet@aphp.fr

Study Design

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

Model Details: National, multicenter, open-label randomized, 2-arm, phase III superiority trial

Study Record Dates

• First Submitted: June 27, 2024
• First Posted: July 15, 2024
• Study Start: June 27, 2025
• Primary Completion (Estimated): June 27, 2028
• Study Completion (Estimated): June 27, 2031
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)