Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer

Study Overview
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Brief Summary
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This study is for people with colorectal cancer, who have tumors that cannot be completely removed by surgery. This study is being done to find out how long it takes tumors to grow after patients receive the drugs capecitabine, oxaliplatin and bevacizumab. Capecitabine (also called Xeloda) is a drug that has been approved by the FDA for treatment of advanced colorectal cancer. Capecitabine prevents some colorectal cancer cancer cells from reproducing, and causes some of them to die. Oxaliplatin (also called Eloxatin) has also been approved by the FDA for treatment of advanced colorectal cancer. Oxaliplatin prevents some colorectal cancer cells from reproducing. Bevacizumab is an investigational drug. Bevacizumab is an antibody (a protein that acts against a specific substance) directed against vascular endothelial growth factor (VEGF). VEGF promotes the growth of blood vessels that bring nutrients to cells. Bevacizumab inhibits the growth of colon cancer cells, by blocking the effects of VEGF. The combination of the drugs used in this study is experimental. The purpose of this study is to see how long it takes patients' tumors to grow when they are taking this combination of drugs.

Official Title
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Phase II Study of Oxaliplatin, Capecitabine and Bevacizumab as First Line Treatment for Patients With Advanced Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: Bevacizumab
* Drug: Capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed metastatic or recurrent colorectal tumors with no previous treatment for advanced disease. Age greater than or equal to 18 years SWOG performance status 0-1. At least one measurable lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Minimum indicator lesion size: > 10 mm measured by spiral CT or >20mm measured by conventional techniques. Have a negative serum pregnancy test within 7 days prior to initiation of chemotherapy (female patients of childbearing potential). Availability of tumor biopsy (paraffin embedded or fresh frozen) at the time of diagnosis and/or prior to study entry is required. Patients must agree to have a 20 cc blood sample drawn in addition to routine labs with each cycle of chemotherapy. Exclusion Criteria: Pregnant or lactating woman. Life expectancy < 3 months. Serious, uncontrolled, concurrent infection(s) or illness(es) Any prior oxaliplatin treatment, with the exception of adjuvant therapy given > 12 months prior to the beginning of study therapy Prior unanticipated severe reaction to fluoropyrimidine therapy, known hypersensitivity to 5-fluorouracil, or known DPD deficiency Prior unanticipated severe reaction or hypersensitivity to platinum based compounds. Treatment for other carcinomas within the last five years, except cured non-melanoma skin and treated in-situ cervical cancer. Current, recent (within 4 weeks of first infusion on this study) or planned participation in an investigational drug study. Clinically significant cardiac disease (e.g. congestive heart failure, symptomatic coronary artery disease and cardiac arrhythmias not well controlled with medication) within the last 6 months. History of clinically significant interstitial lung disease and/or pulmonary fibrosis. History of persistent neurosensory disorder including but not limited to peripheral neuropathy. Presence of central nervous system or brain mets. Major surgery, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study. Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome. Any of the following laboratory values: Abnormal hematologic values (neutrophils < 1.5 x 109/L, platelet count < 100 x 109/L) Urine protein: creatinine ratio >/= 1.0 Impaired renal function with estimated creatinine clearance < 30 ml/min as calculated with Cockroft et Gault equation: Serum bilirubin > 1.5 x upper normal limit. ALT, AST > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases) Alkaline phosphatase > 2.5 x upper normal limit (or > 5 x upper normal limit in the case of liver metastases or > 10 x upper normal limit in the case of bone disease) Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to Day 0 Blood pressure > 150/100 mmHg Unstable angina New York Heart Association (NYHA) Grade II or greater congestive heart failure History of myocardial infarction or stroke within 6 months Clinically significant peripheral vascular disease Evidence of bleeding diathesis or coagulopathy History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0. Serious, non-healing wound, ulcer or bone fracture Carcinoma of any histology in close proximity to a major vessel, cavitation or history of hemoptysis. Completion of previous adjuvant chemotherapy regimen < four weeks prior to the start of study treatment (within six weeks of study treatment for mitomycin C and nitroureas), or with related toxicities unresolved prior to the start of study treatment.

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: Oxaliplatin, followed by Bevacizumab with Capecitabine<br>oxaliplatin 85 mg/m2 q 14 days, followed by bevacizumab 5 mg/kg q 14 days, with capecitabine 750 mg/m2 bid daily | Drug: Oxaliplatin<br> <br> * Other names: Eloxatin;Drug: Bevacizumab<br> <br> * Other names: Avastin;Drug: Capecitabine<br> <br> * Other names: Xeloda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Median Time for Progression Free Survival | Progression-free survival was measured from the start of treatment until the time the subject is first recorded as having disease progression (progression = 20% increase in sum of longest diameters of target measurable lesions over smallest sum observed or baseline, progression of non-measurable disease in the opinion of treating physician, appearance of new lesion/site, death due to disease), or death due to any cause. If a subject has not progressed or died, progression-free survival was censored at the time of last follow-up or the start of another treatment, whichever came first. | Up to 6 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Grade 3 or Higher Toxicity | Summary of grade 3 (per CTCAE v3.0) or higher toxicities which generally is described as a severe adverse reaction or symptom. | Baseline, every 2 weeks of each cycle, and at end of treatment, up to 18 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal, cancer