Study of Cetuximab, Oxaliplatin, 5-FU/LV Versus Oxaliplatin, 5-FU/LV in Patients With Previously Treated Metastatic, EGFR-Positive Colorectal Cancer

Study Overview
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Brief Summary
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The purpose of this study is to compare overall survival in patients with previously-treated metastatic, epidermal growth factor receptor (EGFR)-positive colorectal cancer treated with oxaliplatin, 5-fluorouracil and leucovorin (FOLFOX4) and cetuximab with FOLFOX4 alone.

Official Title
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A Phase 3 Randomized Multicenter Study of Cetuximab, Oxaliplatin, 5-Fluorouracil, and Leucovorin vs. Oxaliplatin, 5-Fluorouracil, and Leucovorin in Subjects With Previously Treated Metastatic, EGFR-Positive Colorectal Carcinoma

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: cetuximab
* Drug: oxaliplatin
* Drug: leucovorin
* Drug: 5-fluorouracil
* Drug: 5-fluorouracil
* Biological: cetuximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented colorectal cancer which is EGFR-positive and is metastatic. Prior irinotecan, alone or in combination, as first-line treatment of metastatic disease. Exclusion Criteria: A serious uncontrolled medical disorder that, in the opinion of the Investigator, would impair the ability of the subject to receive protocol therapy. Known dihydropyrimidine dehydrogenase (DPD) deficiency. Known metastases in the central nervous system. Symptomatic sensory or peripheral neuropathy. More than one prior chemotherapy regimen for the treatment of metastatic colorectal cancer. Prior oxaliplatin therapy. Prior cetuximab or other therapy which targets the EGF pathway. Prior chimerized or murine monoclonal antibody therapy.

Ages Eligible for Study
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Minimum Age: 18 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: Cetuximab+FOLFOX4<br>Day 1 - cetuximab loading dose of 400 mg/m2 IV, infused over 2 hours; oxaliplatin (85 mg/m2) simultaneously with leucovorin (200 mg/m2), followed by 5-FU 400 mg/m2 IV bolus followed by 5-FU 600 mg/m2 as a 22-hour continuous infusion Day 2 - leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 IV bolus followed by another dose of 5-FU 600 mg/m2 as a 22-hour continuous infusion Day 8 - cetuximab maintenance dose of 250 mg/m2 IV infused over 60 minutes | Biological: cetuximab<br>* 400 mg/m2 IV<br>* Other names: Erbitux™;Drug: oxaliplatin<br>* 85 mg/m2 IV<br>* Other names: Eloxatin®;Drug: leucovorin<br>* 200 mg/m2 IV<br>* Other names: Wellcovorin®;Drug: 5-fluorouracil<br>* 400 mg/m2 IV<br>* Other names: 5-FU;Drug: 5-fluorouracil<br>* 600 mg/m2 IV<br>* Other names: 5-FU;Biological: cetuximab<br>* 250 mg/m2 IV<br>* Other names: Erbitux™;|
| Active Comparator: FOLFOX4.<br>Day 1 - oxaliplatin (85 mg/m2) simultaneously with leucovorin (200 mg/m2), followed by 5-FU 400 mg/m2 IV bolus followed by 5-FU 600 mg/m2 as a 22-hour continuous infusion. Day 2 - leucovorin 200 mg/m2 followed by 5-FU 400 mg/m2 IV bolus followed by another dose of 5-FU 600 mg/m2 as a 22-hour continuous infusion. | Drug: oxaliplatin<br>* 85 mg/m2 IV<br>* Other names: Eloxatin®;Drug: leucovorin<br>* 200 mg/m2 IV<br>* Other names: Wellcovorin®;Drug: 5-fluorouracil<br>* 400 mg/m2 IV<br>* Other names: 5-FU;Drug: 5-fluorouracil<br>* 600 mg/m2 IV<br>* Other names: 5-FU;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare overall survival in subjects with previously-treated metastatic, epidermal growth factor receptor (EGFR)-positive colorectal cancer treated with oxaliplatin, 5-FU, and LV (FOLFOX4) and cetuximab with FOLFOX4 alone. |  | Every six weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the response rates between the two treatment arms. |  | Every six weeks | 
| Compare progression-free survival between the two treatment arms. |  | Every six weeks | 
| Duration of response within each treatment arm. |  | Every six weeks | 
| Time to response within each treatment arm. |  | Every six weeks | 
| Compare the safety profiles between the two treatment arms. |  | Every six weeks | 
| Compare the quality of life (QOL)between the two treatment arms. |  | Every six weeks | 
| Conduct an economic assessment comparing healthcare resource utilization between the two treatment arms. |  | Every six weeks |