A Study of Avastin (Bevacizumab) in Combination With mFOLFOX6 in Treatment-Naïve Patients With Metastatic Colorectal Cancer With or Without K-RAS Mutations, and Comparison to Cetuximab

Study Overview
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Brief Summary
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This randomized, open-label study will evaluate the safety and efficacy of Avastin (Bevacizumab) added to standard mFOLFOX6 chemotherapy in treatment-naïve patients with Stage IV metastatic colorectal cancer. According to K-RAS gene mutation status, patients will be assigned or randomized to receive either Avastin 5 mg/kg intravenously (iv) on Day 1 of each 2-week cycle or cetuximab 400 mg/m2 iv on Day 1 followed by 250 mg/m2 iv every week, in addition to mFOLFOX6 every 2 weeks. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: cetuximab
* Drug: mFOLFOX6


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients >/= 18 years of age Histologically confirmed adenocarcinoma of the colon or rectum Stage IV metastatic disease with at least one measurable metastatic lesion according to RECIST criteria Tumour tissue sample available for assessment of K-RAS and BRAF genes Prior radiotherapy must have been completed 4 weeks before randomization Adequate bone marrow, kidney and liver function Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Exclusion Criteria: Previous chemotherapy for metastatic disease Completion of adjuvant treatment for colorectal cancer (Stage I, II and III) in the 12 months preceding randomization Prior treatment with bevacizumab, cetuximab or other EGFR inhibitors Clinical or radiographic evidence of brain metastases Clinically significant cardiovascular disease or disorder History of neoplastic disease other than colorectal cancer in the 3 years prior to start of study treatment, except for successfully treated non-invasive carcinomas such as cervical cancer in situ, basal cell carcinoma of the skin or superficial bladder tumours HIV, hepatitis B or C infection

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: K-RAS mutated<br> | Drug: bevacizumab [Avastin]<br>* 5 mg/kg iv on Day 1 of each 2-week cycle until disease progression, unacceptable toxicity or withdrawal of consent<br>Drug: mFOLFOX6<br>* Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent<br>|
| Experimental: K-RAS native A<br> | Drug: bevacizumab [Avastin]<br>* 5 mg/kg iv on Day 1 of each 2-week cycle until disease progression, unacceptable toxicity or withdrawal of consent<br>Drug: mFOLFOX6<br>* Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent<br>|
| Active Comparator: K-RAS native B<br> | Drug: cetuximab<br>* 400 mg /m2 iv on Day 1, followed by 250 mg/m2 every week until disease progression, unacceptable toxicity or withdrawal of consent<br>Drug: mFOLFOX6<br>* Standard mFOLFOX6 chemotherapy, 2-week cycles until disease progression, unacceptable toxicity or withdrawal of consent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival: native versus mutated K-RAS; tumour assessments according to RECIST criteria |  | up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | up to 4 years | 
| Objective response rate |  | 4 years | 
| Safety: Incidence of adverse events |  | 4 years | 
| Quality of Life: European Organisation for Research and Treatment of Cancer Quality of Life questionnaire (EORTC QLQ-C30) |  | up to 4 years | 
| Progression-free survival: comparison of the two treatment regimens in the native K-RAS arms |  | up to 4 years |