Avastin and Chemotherapy Followed by a KRAS Stratified Randomization to Maintenance Treatment for First Line Treatment of Metastatic Colorectal Cancer.

Study Overview
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Brief Summary
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Patients with metastatic colorectal cancer will be treated with chemotherapy according to investigators choice. In addition to chemotherapy treatment, treatment with bevacizumab will be given concomitantly. This treatment will continue during 18 weeks. Meanwhile, the patients KRAS status will be tested. After having fulfilled these 18 weeks of induction treatment, patients who has responded (complete response/partial response versus stable disease) will be randomized to maintenance treatment. Patients with KRAS WT will be randomized to either bevacizumab alone, or to bevacizumab and erlotinib. Patient with KRAS mutation will be randomized to either bevacizumab, or metronomic capecitabine. Translational research is performed, with purpose to find predictive factors in blood and tumor tissue.

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: bevacizumab, erlotinib
* Drug: bevacizumab
* Drug: bevacizumab
* Drug: low dose capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Untreated metastatic colorectal carcinoma Age 18 yrs or over Measurable disease according to Response Evaluation Criteria in solid Tumors (RECIST criteria) ECOG performance status 0 or 1 Life expectancy more than 3 months Adequate haematological, renal and liver function Tumor tissue available for determination of KRAS mutational status Blood sample and paraffin embedded tumor tissue for translational research Exclusion Criteria: Adjuvant therapy within 6 months CNS metastases Clinically significant atherosclerotic vascular disease

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 |
| --- | --- |
| Active Comparator: bevacizumab and erlotinib (KRAS WT)<br> | Drug: bevacizumab, erlotinib<br>* bevacizumab 7.5 mg/kg body weight every third week, erlotinib 150 mg daily<br>* Other names: Avastin, Tarceva;|
| Active Comparator: bevacizumab (KRAS WT)<br> | Drug: bevacizumab<br>* bevacizumab 7.5 mg/kg body weight every third week<br>* Other names: Tarceva;|
| Active Comparator: bevacizumab (KRAS mutated)<br> | Drug: bevacizumab<br>* bevacizumab 7.5 mg/kg body weight every third week.<br>* Other names: Avastin;|
| Active Comparator: low dose capecitabine (KRAS mutated)<br> | Drug: low dose capecitabine<br>* capecitabine 500 mg twice daily<br>* Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate that maintenance treatment with bevacizumab + erlotinib following first line chemo- and anti-angiogenetic therapy results in a significant increase in progression free survival (PFS) compared to treatment with only bevacizumab. |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To explore the activity of bevacizumab and low dose metronomic capecitabine in patients with KRAS mutated tumors. |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Untreated, First line, Chemotherapy, Maintenance treatment, KRAS wt, KRAS mutated, Anti-angiogenetic treatment, Metronomic capecitabine, bevacizumab, erlotinib, Translational research