Combination Chemotherapy With or Without Cetuximab in Treating Patients With Stage III Colon Cancer That Was Completely Removed By Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as oxaliplatin, leucovorin, or fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. 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. Cetuximab may also stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy with or without cetuximab after surgery may kill any remaining tumor cells and keep colon cancer from coming back. It is not yet known whether giving combination chemotherapy together with cetuximab is more effective than giving combination chemotherapy alone in treating colon cancer. PURPOSE: This randomized phase III trial is studying combination chemotherapy and cetuximab to see how well they work compared to combination chemotherapy alone in treating patients with stage III colon cancer that was completely removed by surgery.

Detailed Description
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OBJECTIVES: Primary Compare the disease-free survival rates in patients with completely resected stage III colon cancer treated with adjuvant oxaliplatin, leucovorin calcium, and fluorouracil with vs without cetuximab. Secondary Compare the 3-year disease-free survival rate and 5-year overall survival rate in patients treated with these regimens. Compare the overall survival of patients treated with these regimens. Compare the treatment compliance of patients treated with these regimens. Determine the prognostic factors and markers predictive for relapse and/or treatment efficacy in patients treated with these regimens. Compare the safety of these regimens in these patients. OUTLINE: This is an open-label, randomized, controlled, multicenter study. Patients are stratified according to obstruction/perforation status (no obstruction and no perforation vs obstruction and/or perforation), N stage (N1 vs N2), and T stage (T1-3 vs T4). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients receive oxaliplatin IV over 2 hours on day 1 and leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 22 hours on days 1 and 2. Arm II: Patients receive chemotherapy as in arm I plus cetuximab IV over 1-2 hours on days 1 and 8. In both arms, treatment repeats every 14 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for approximately 5 years. PROJECTED ACCRUAL: A total of 2,000 patients will be accrued for this study.

Official Title
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Adjuvant Treatment of Fully Resected Stage III Colon Cancer With FOLFOX-4 Versus FOLFOX-4 Plus Cetuximab

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Folfox
* Drug: Cetuximab


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed stage III adenocarcinoma of the colon Must have undergone curative resection (R0) within the past 28-56 days No radiotherapy prior to surgery carcinoembryonic antigen (CEA) ≤ 1.5 times upper limit of normal (ULN) after surgery No rectal cancer located within 15 cm from the anal verge by endoscopy or under the peritoneal reflection at surgery No metastatic spread at baseline assessment No prior or concurrent CNS disease by physical exam PATIENT CHARACTERISTICS: Performance status WHO 0-1 Life expectancy At least 5 years Hematopoietic WBC ≥ 3,000/mm^3 Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Hepatic Bilirubin ≤ 1.5 times ULN AST and ALT ≤ 2.5 times ULN Alkaline phosphatase ≤ 1.5 times ULN Renal Creatinine ≤ 1.5 times ULN Cardiovascular No coronary artery disease No myocardial infarction within the past 12 months No high risk of uncontrolled arrhythmia Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No inflammatory bowel disease No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No significant traumatic injury within the past 28 days No known hypersensitivity to any of the components of the study drugs No medical, geographical, sociological, psychological, or legal condition that would preclude study participation No peripheral neuropathy ≥ grade 1 No other significant disease that would preclude study participation PRIOR CONCURRENT THERAPY: Chemotherapy No prior chemotherapy Radiotherapy See Disease Characteristics No prior abdominal or pelvic irradiation Surgery See Disease Characteristics Recovered from prior surgery More than 28 days since prior major surgical procedure or open biopsy No concurrent major surgical procedure

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Folfox+Cetuximab<br>FOLFOX-4 Cetuximab alone every 2 weeks | Drug: Folfox<br> <br> Drug: Cetuximab<br> <br> |
| Active Comparator: Folfox<br>FOLFOX-4 alone every 2 weeks | Drug: Folfox<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease-free survival | DFS time in the ITT KRAS wild-type population | 3-years DFS | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage III colon cancer, adenocarcinoma of the colon