Bevacizumab and Combination Chemotherapy in Treating Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as irinotecan, fluorouracil, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well bevacizumab given together with combination chemotherapy works in treating patients with metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Evaluate the objective response (complete and partial) rate in patients with metastatic colorectal adenocarcinoma treated with bevacizumab and modified FOLFIRI 3 chemotherapy. Secondary Determine progression-free and overall survival. Determine the tolerance to this regimen. Evaluate the resectability rate. Evaluate biological markers predictive of the efficacy of this regimen. OUTLINE: This is a multicenter study. Patients receive bevacizumab IV over 30-90 minutes on day 1, irinotecan hydrochloride IV over 90 minutes on days 1 and 3, and fluorouracil IV continuously over 46 hours on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. At 14 days after completing chemotherapy, patients with progressive or stable disease receive maintenance therapy comprising bevacizumab and capecitabine. Biological specimens are collected at baseline and before the fourth course of chemotherapy. After completion of study therapy, patients are followed every 3 months for 2 years.

Official Title
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Phase II Study Evaluating the Association of Bevacizumab and Chemotherapy of the Type Modified FOLFIRI 3 in Patients With Metastatic Colorectal Adenocarcinoma

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: capecitabine
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Other: diagnostic laboratory biomarker analysis


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed adenocarcinoma of the colon or rectum Previously untreated metastatic disease Measurable disease by RECIST Must not be located in a prior radiation field No cerebral or meningeal metastases PATIENT CHARACTERISTICS: Inclusion criteria: WHO performance status 0-1 Life expectancy > 12 weeks Absolute neutrophil count ≥ 1,000/mm³ Platelet count ≥ 100,000/mm³ Bilirubin ≤ 1.5 times upper limit of normal (ULN) Transaminases ≤ 2 times ULN (5 times ULN if liver metastases present) Alkaline phosphatase ≤ 2 times ULN (5 times ULN if liver metastases present) Creatinine ≤ 130 μmol/L OR creatinine clearance ≥ 30 mL/min Proteinuria < 2+ or urine protein ≤ 1 g/24 hours Not pregnant or nursing Fertile patients of must use effective contraception Exclusion criteria: Uncontrolled cardiac disease Prior cerebral vascular accident Uncontrolled arterial hypertension Severe renal or hepatic insufficiency Prior arteriopathy Bleeding disorder or nonhealing wound Coagulopathy Other malignancy within the past 2 years except basal cell or squamous cell skin cancer or curatively treated carcinoma of the cervix Psychiatric disorder compromising comprehension or participation in the study Intestinal occlusion or subocclusion not caused by medical therapy PRIOR CONCURRENT THERAPY: Inclusion criteria: See Disease Characteristics Exclusion criteria: Prior adjuvant bevacizumab or irinotecan hydrochloride Concurrent aspirin (> 325 mg/day) or therapeutic anticoagulants Surgery in the past 28 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Non-Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: capecitabine|nan|
|Drug: fluorouracil|nan|
|Drug: irinotecan hydrochloride|nan|
|Other: diagnostic laboratory biomarker analysis|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response (complete and partial) rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 
| Overall survival |  |  | 
| Tolerance |  |  | 
| Resectability rate |  |  | 
| Biomarkers predictive of efficacy |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV colon cancer, stage IV rectal cancer, adenocarcinoma of the colon, adenocarcinoma of the rectum