Adjuvant FOLFIRI Based-chemotherapy After Resection of CLM Responding to Preoperative FOLFIRI
NCT Number: NCT06501482
Acronym: IRIMAD
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE3
Conditions: Colorectal Cancer|Colorectal Liver Metastases
Interventions: DRUG: Postoperative reintroduction of FOLFIRI based chemotherapy
Sponsor: Assistance Publique - Hôpitaux de Paris
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 254
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-09-30
Completion Date: 2030-09-30
Locations: Hôpital Kremlin Bicêtre, Paris, Île-de-france, 75010, France

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.

Primary Outcome Measures: 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 Outcome Measures: The overall survival rate, All patients will be followed-up for at least 3 year after randomization or until death. Overall survival is defined as survival duration from the time of randomization to death. Patients who are still alive when last traced will be censored at the date of last follow-up., 3 years|The Liver-free survival rate, Liver-free survival is defined as survival duration from the time of randomization to first liver recurrence., 3 years
Other Outcome Measures: The Extra -hepatic recurrence rate, The extra-hepatic recurrence rate is the rate of cancer relapse aside the liver. This rate will be evaluated at 3 years and at the date of last follow-up., 3 years|The safety including chemotherapy associated toxicity assessed by International Common Terminology Criteria for Adverse Events (CTCAE) grading system, All adverse events will be recorded in the electronic case report form (eCRF) using the International Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 for adverse event reporting (see chapter 10. Safety assessment)., 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, The ability to administrate a total of 12 cycles of FOLFIRI-based chemotherapy including preoperative treatment: Compliance with study protocol will be defined as completion of full dose planned preoperative treatment in each treatment arm. Any deviation and cause of deviation (toxicity, progression, physician or patient preference) from the protocol will be collected, 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|The rate of treatment of recurrence, Among patients who develop disease recurrence and who therefore achieved the primary endpoint, a proportion will be treated with curative intent including chemotherapy and local therapy (radiofrequency ablation or surgery). The proportion of patients undergoing treatment of recurrence with curative intent in will be evaluated in both groups, Every 3 months for 2 years and then every 6 months for 3 years|The quality of life, Quality of life assessed by QLQ C-30, 1 year