Cetuximab and Combination Chemotherapy as First-Line Therapy in Treating Patients With Metastatic Colorectal Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving cetuximab together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cetuximab together with combination chemotherapy works as first-line therapy in treating patients with metastatic colorectal cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Determine the complete response rate in patients with metastatic colorectal cancer treated with cetuximab and FOLFIRINOX chemotherapy comprising oxaliplatin, irinotecan hydrochloride, leucovorin calcium, and fluorouracil as first-line therapy. Secondary Determine the objective response rate in patients treated with this regimen. Assess the tolerability of this regimen in these patients. Determine the time to response and time to progression in patients treated with this regimen. Determine the survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive cetuximab IV over 1-2 hours on days 1 and 8. Patients also receive FOLFIRINOX chemotherapy comprising oxaliplatin IV over 2 hours, irinotecan hydrochloride IV over 30-90 minutes, and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 15 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 3 months.

Official Title
-----------------
Phase II Study Evaluating the Efficacy and Safety of cétuximab Associated With the Protocol FOLFIRINOX (LV5FU Simplified Combined With Irinotecan and Oxaliplatin) in the First Line Treatment in Patients With Metastatic Colorectal Cancer Expressing EGFR or Not

Conditions
-----------------
Colorectal Cancer

Intervention / Treatment
-----------------
* Biological: cetuximab
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium
* Drug: oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
DISEASE CHARACTERISTICS: Histologically confirmed colorectal cancer Metastatic, unresectable disease May or may not express the EGFR gene Measurable disease, defined as ≥ 1 measurable lesion by MRI or CT scan Lesion must be outside an irradiated area PATIENT CHARACTERISTICS: WHO performance status 0-1 Life expectancy > 3 months ANC ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL Total bilirubin ≤ 1.5 times upper limit of normal (ULN) Transaminases ≤ 2.5 times ULN (5 times ULN if hepatic metastases are present) Creatinine ≤ 1.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception No peripheral or symptomatic neuropathy ≥ grade 2 (NCI-CTCAE) No complete or partial intestinal blockage No intestinal inflammatory disease (e.g., Crohn's disease or ulcerative colitis) No chronic diarrhea No severe unstable cardiac disease (despite treatment) No myocardial infarction within the past 6 months No neurological or psychiatric illness, including epilepsy or dementia No uncontrolled active infection No other prior or concurrent malignancy within the past 5 years except for curatively treated basal cell skin cancer No psychological, familial, social, or geographic reason that would preclude study follow-up PRIOR CONCURRENT THERAPY: No prior chemotherapy for metastatic disease Prior fluorouracil-based adjuvant chemotherapy allowed provided it was administered ≥ 4 weeks ago At least 4 weeks since prior and no other concurrent experimental therapy No prior irinotecan hydrochloride, oxaliplatin, or monoclonal antibody No prior intestinal resection (e.g., hemicolectomy or extended resection of the small intestine)

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
Intervention Model: Single Group Assignment


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ERBIRINOX<br>5FU + Irinotecan + Oxaliplatine + Cetuximab | Biological: cetuximab<br> <br> Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> Drug: oxaliplatin<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response rate |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  | 6 months | 
| Adverse events by using NCI-CTC |  | 6 months | 
| Time to response |  | 6 months | 
| Time to progression |  | 6 months | 
| Survival |  | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV colon cancer, stage IV rectal cancer, recurrent colon cancer, recurrent rectal cancer