Combination Chemotherapy in Treating Patients With Colorectal Cancer and Resectable Metastases

Study Overview
=================
Brief Summary
-----------------
PURPOSE: This randomized phase III trial is studying two different combination chemotherapy regimens to compare how well they work in treating patients with colorectal cancer and resectable metastases.

Detailed Description
-----------------
OBJECTIVES: Primary Compare the 2-year disease-free survival rate in patients treated with these regimens. Secondary Compare the overall survival of patients treated with these regimens. Compare the tolerability of these regimens in these patients. Compare the quality of life of patients treated with these regimens. Compare the objective response rate, postoperative complication rate, and transfusing rate in patients having metastasis surgery, Determine the pharmacogenetics of these regimens in these patients. OUTLINE: This is a randomized, open-label, multicenter phase III study. Patients are stratified according to prior chemotherapy (perioperative vs postoperative), prior treatment (surgery only vs radiotherapy with or without surgery), and Blumgart score (0-1 vs 2-3 vs 4-5). Patients are randomized to 1 of 2 treatment arms. Arm I (FOLFOX 4): Patients receive FOLFOX 4 combination chemotherapy comprising oxaliplatin 85mg/m² IV over 2 hours, leucovorin calcium IV over 2 hours, fluorouracil IV bolus /15min and fluorouracil continuously over 22 hours on day 1. Treatment repeats every 2 weeks for 12 courses in the absence of disease progression or unacceptable toxicity. Arm II (FOLFOX 7 and FOLFIRI): Patients receive FOLFOX 7 combination chemotherapy comprising high-dose oxaliplatin 130mg/m² IV over 2 hours and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive FOLFIRI combination chemotherapy comprising irinotecan hydrochloride 180mg/m² IV over 30-90 minutes and leucovorin calcium and fluorouracil IV bolus /15min on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for 6 courses in the absence of disease progression or unacceptable toxicity. Patients in both arms who have undergone prior resection of metastatic lesions may undergo surgery after 6 courses of chemotherapy or after chemotherapy is completed. Quality of life is assessed at baseline and after courses 4, 8, and 12. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 284 patients will be accrued for this study.

Official Title
-----------------
Essai De Phase III De Chimiotherapie Par FOLFOX 4 Ou Par Une Succession FOLFOX 7 - FOLFIRI Chez Des Patients Ayant Des Metastases Resecables D'Origine Colorectale - MIROX

Conditions
-----------------
Chemotherapy, Colorectal Cancer, Metastatic Cancer

Intervention / Treatment
-----------------
* Drug: oxaliplatin, folinic acid, fluorouracil
* Drug: oxaliplatin, irinotecan, folinic acid, fluorouracil


Participation Criteria
=================
Eligibility Criteria
-----------------
MAIN ELIGIBILITY CRITERIA DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum Resectable or resected metastatic disease, PATIENT CHARACTERISTICS: WHO performance status 0-2 Alkaline phosphatase ≤ 5 times upper limit of normal (ULN) Bilirubin ≤ 2 times normal Creatinine ≤ 135 mmol/L or creatinine clearance ≥ 60 mL/min SGOT and SGPT ≤ 3 times ULN No peripheral neuropathy that affects normal functions No unresolved complications from prior surgery PRIOR CONCURRENT THERAPY: At least 1 year since prior FOLFOX 4 or FOLFIRI regimen in the adjuvant setting No concurrent participation in another clinical trial Recovered from prior therapy

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: FOLFOX4<br> | Drug: oxaliplatin, folinic acid, fluorouracil<br>* folinic acid 200 mg/m² (day 1&2) oxaliplatin 85 mg/m² (day 1) bolus 5FU 400 mg/m² (day 1&2) continuous 5FU 600mg/m² (day 1 to 2)<br>|
| Experimental: FOLFOX7 followed by FOLFIRI<br> | Drug: oxaliplatin, irinotecan, folinic acid, fluorouracil<br>* FOLFOX7 folinic acid 400 mg/m² (day 1) oxaliplatin 130 mg/m² (day 1) continuous 5FU 3000mg/m² (day 1 to 2) FOLFIRI folinic acid 400 mg/m² (day 1) irinotecan 180 mg/m² (day 1) bolus 5FU 400 mg/m² (day 1) continuous 5FU 2400mg/m² (day 1 to 2)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease-free survival |  | 2-year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 2-year, 3-year, 5-year | 
| Tolerability |  | 2-year | 
| Quality of life |  | 2-year | 
| Pharmacogenetics |  | 2-year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
adenocarcinoma of the colon, stage IV colon cancer, adenocarcinoma of the rectum, stage IV rectal cancer, resectable metastases