Combination Chemotherapy and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects of giving combination chemotherapy together with bevacizumab and to see how well it works in treating patients with metastatic colorectal cancer.

Detailed Description
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OBJECTIVES: Primary Evaluate the objective response (RECIST criteria) at 6 months associated with FOLFIRI and bevacizumab therapy. Evaluate the tolerability (NCI CTC v. 2.0 criteria) of this treatment. Secondary Evaluate progression-free survival and overall survival. Determine the time to treatment failure. Evaluate the quality of life (EuroQOL EQ5D questionnaire). Explore the prognostic factors associated with the tolerability and efficacy of this treatment. OUTLINE: This is a multicenter study. Patients are stratified according to genotype (UCT1A1*1/ UCT1A1*1 vs UCT1A1*1/ UCT1A1*28). Patients receive bevacizumab IV over 30-90 minutes, irinotecan hydrochloride IV over 90 minutes, leucovorin calcium IV over 2 hours, and fluorouracil IV over 46 hours on day 1. Treatment repeats every 2 weeks in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, every 4 courses, and then every 2 months after the completion of study therapy. After completion of study therapy, patients are followed every 2-3 months.

Official Title
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Chemotherapy With FOLFIRI Plus Bevacizumab (AvastinR) in Patients With Metastatic Colorectal Cancer Bearing Genotype UGT1A1*1/UGT1A1*1 or UGT1A1*1/UGT1A1*1/UGT1A1*28: Prospective, Phase II, Multicenter Study

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Biological: bevacizumab
* Drug: fluorouracil
* Drug: irinotecan hydrochloride
* Drug: leucovorin calcium


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of metastatic adenocarcinoma of the colon or rectum Not curable by surgery Genotype UGT1A1*1/UGT1A1*1 or UGT1A1*1/ UGT1A1*28 Measurable disease No original tumor in place No secondary cerebral metastases PATIENT CHARACTERISTICS: Inclusion criteria: WHO performance status 0-2 Life expectancy ≥ 3 months Absolute neutrophil count ≥ 1,500/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 1.5 times normal Alkaline phosphatase ≤ 2.5 times normal (5 times normal if liver involvement) Not pregnant or nursing Negative pregnancy test Fertile patients of must use effective contraception Exclusion criteria: Progressive gastrointestinal ulcer, hemorrhagic ulcer, or perforation in the past 6 months Enteropathy or chronic diarrhea Proteinuria > 500 mg/24 hours Active cardiac disease Uncontrolled hypertension Myocardial infarction in the past 12 months Angina NYHA grade II-IV congestive heart disease Severe arrhythmia even with treatment Peripheral vascular disease ≥ grade II Nonhealing wound, ulcer, or severe bone fracture Hemorrhagic diatheses or coagulopathy Severe or uncontrolled infection Severe or uncontrolled medical condition Other malignant disease in the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the uterine cervix Severe traumatic injury within the past 4 weeks PRIOR CONCURRENT THERAPY: No prior chemotherapy for metastatic disease One prior regimen of chemotherapy in the neoadjuvant or adjuvant setting for the original tumor allowed At least 6 months since prior chemotherapy No prior irinotecan hydrochloride or bevacizumab No oral or parenteral anticoagulant therapy within the past 10 days Warfarin allowed provided INR < 1.5 No major surgery or biopsy within the past 4 weeks No puncture in the past 7 days No planned major surgery No concurrent daily or chronic aspirin (> 325 mg/day), anti-inflammatories, or steroids No other concurrent anticancer therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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: FOLFIRI fort plus bevacizumab<br>Bevacizumab 5 mg/kg D1, irinotecan 260 mg/m2 D1, LV 400 mg/m2 D1, 5FU 400 mg/m2 IV bolus D1, and 5FU 2,400 mg/m2 46-hour infusion D1-2 every 2 weeks. Treatment was started within 2 weeks after inclusion in the study. | Biological: bevacizumab<br> <br> Drug: fluorouracil<br> <br> Drug: irinotecan hydrochloride<br> <br> Drug: leucovorin calcium<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response at 6 months by RECIST |  | 6 months | 
| Tolerability evaluated by NCI CTC v. 2.0 criteria |  | From Inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free and overall survival |  | From Inclusion | 
| Time to treatment failure |  | From Inclusion | 
| Quality of life using the EuroQOL EQ5D questionnaire |  | From Inclusion | 

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