Adjuvant FOLFIRI Based-chemotherapy After Resection of CLM Responding to Preoperative FOLFIRI
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorAssistance Publique - Hôpitaux de Paris
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Postoperative reintroduction of FOLFIRI based chemotherapy
DrugPostoperative 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
Treatment groups
254 Participants
are divided into 2 treatment groupsGroup A: Postoperative FOLFIRI groupExperimental treatment 1 intervention
Group B: No treatment group (control group)No intervention 0 interventions
Trial outcomes
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.
Time frame
3 yearsSecondary outcomes
1
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.
Time frame
3 years2
The Liver-free survival rate
Liver-free survival is defined as survival duration from the time of randomization to first liver recurrence.
Time frame
3 yearsOther outcomes
1
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.
Time frame
3 years2
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).
Time frame
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 years3
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
Time frame
At each cycle of postoperative FOLFIRI chemotherapy administration for a total of 12 cycles perioperative (including the preoperative chemotherapy) and each cycle is 15 days4
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
Time frame
Every 3 months for 2 years and then every 6 months for 3 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov