Bevacizumab and Cetuximab in Combination With FOLFOX6 in Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This trial will evaluate the combination of modified infusional 5-fluorouracil/ leucovorin, oxaliplatin (FOLFOX6), bevacizumab, and cetuximab in patients with metastatic colorectal cancer. FOLFOX6 has proven to be a safe and effective regimen in first line treatment of advanced colorectal cancer. The role of epidermal growth factor (EGFR) inhibitors in an earlier treatment setting in combination with optimal chemotherapy regimens is an important emerging question.

Detailed Description
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All patients received cetuximab: 400 mg/m2 (first cycle only) administered intravenously (IV) on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8. Day 1 cetuximab was immediately followed by bevacizumab 5 mg/kg IV, oxaliplatin 85 mg/m2 IV, and 5-fluorouracil 400 mg/m2 IV bolus, followed by 2400 mg/m2 administered as a continuous infusion over 46 hours via a pump (outpatient) and leucovorin 350 mg IV (modified FOLFOX6). Cycles were 14 days.

Official Title
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A Randomized Phase II Study of Modified FOLFOX6 (Infusional 5-Fluorouracil/Leucovorin, Oxaliplatin) and Bevacizumab With or Without Cetuximab in Patients With Metastatic Colorectal Cancer

Conditions
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Colon Cancer

Intervention / Treatment
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* Drug: Bevacizumab
* Drug: Cetuximab
* Drug: 5-fluorouracil
* Drug: Leucovorin
* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be included in the study, you must meet the following criteria: Metastatic colorectal cancer confirmed by a biopsy sample 18 years of age or older Evidence of disease progression at time of study entry At least one prior adjuvant chemotherapy regimen No prior therapy for metastatic disease Measurable disease Able to perform activities of daily living with minimal assistance Adequate bone marrow, kidney, and liver function Tumor tissue available for assessment of EGFR Signed informed consent Exclusion Criteria: You cannot participate in the study if any of the following apply to you: Treatment with a previous regimen for metastatic disease Prior treatment with any EGFR inhibitor or anti-angiogenic agents Brain or nervous system metastases History of severe thromboembolic event Clinical evidence or history of bleeding or coagulopathy History of stroke or heart attack within six months Poorly controlled hypertension Non-healing wound, ulcer, or bone fracture History of abdominal fistula, perforation, or abscess within six months Other uncontrolled or significant disease or medical condition Please note: There are additional inclusion/exclusion criteria. The study center will determine if you meet all of the criteria. If you do not qualify for the trial, study personnel will explain the reasons. If you do qualify, study personnel will explain the trial in detail and answer any questions you may have. You can then decide if you wish to participate.

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Bevacizumab 5 mg/kg IV Cetuximab 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8 5-Fluorouracil 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient) Leucovorin 350 mg IV Oxaliplatin 85 mg/m2 IV | Drug: Bevacizumab<br>* 5 mg/kg IV<br>* Other names: Avastin;Drug: Cetuximab<br>* 400 mg/m2 (first cycle only) IV on day 1 and 250 mg/m2 IV on day 8 with all subsequent cycles 250 mg/m2 IV on days 1 and 8<br>* Other names: Erbitux;Drug: 5-fluorouracil<br>* 400 mg/m2 bolus IV bolus followed by 2400 mg/m2 administered as continuous IV infusion over 46 hours via pump (outpatient)<br>* Other names: Adrucil;Drug: Leucovorin<br>* 350 mg IV<br>* Other names: Folinic Acid;Drug: Oxaliplatin<br>* 85 mg/m2 IV<br>* Other names: Eloxatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR), the Percentage of Patients Who Experience an Objective Benefit From Treatment | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI or CT: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Worsening of Their Disease | Progression Free Survival (PFS) is defined as the interval between the start date of treatment and the date of occurrence of progressive disease or death. | 18 months | 
| Overall Survival (OS), the Length of Time, in Months, That Patients Were Alive From Their First Date of Protocol Treatment Until Death | Measured from the date of first treatment until the date of death from any cause | 36 months | 
| Number of Patients With Adverse Events as a Measure of Safety With FOLFOX6 Combined With Bevacizumab and Cetuximab | The toxicity assessments were made according to the common terminology criteria for adverse events (CTCAE version 3.0) of the National Cancer Institute. Number of participants with Grade 1 to 5 adverse events are reported here. | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colon Cancer