Bevacizumab Plus Fluorouracil and Leucovorin in Treating Patients With Locally Advanced or Metastatic Stage IV Colorectal Cancer That Has Progressed After Standard Chemotherapy

Study Overview
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Brief Summary
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RATIONALE: Bevacizumab may stop the growth of tumor cells by blocking the enzymes necessary for cancer cell growth. Drugs used in chemotherapy such as fluorouracil and leucovorin use different ways to stop tumor cells from dividing so they stop growing or die. Combining bevacizumab with fluorouracil and leucovorin may kill more tumor cells. PURPOSE: Phase II trial to study the effectiveness of combining bevacizumab with fluorouracil and leucovorin in treating patients who have locally advanced or metastatic stage IV colorectal cancer that has progressed after standard chemotherapy.

Detailed Description
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OBJECTIVES: Determine the response rate of patients treated with bevacizumab, fluorouracil, and leucovorin calcium for stage IV colorectal cancer that has progressed after standard chemotherapy. Determine the time to progression and overall survival of patients treated with this regimen. Determine the safety of administering bolus and continuous infusion fluorouracil and leucovorin calcium in patients treated with this regimen. OUTLINE: This is an open-label, multicenter study. Patients receive 1 of 2 treatment regimens. Regimen I: Patients receive bevacizumab IV on days 1, 15, 29, and 42 (every 2 weeks) and leucovorin calcium (CF) IV over 2 hours and fluorouracil (5-FU) IV bolus on days 1, 8, 15, 22, 29, and 36. Regimen II: Patients receive bevacizumab as in regimen I and CF IV over 2 hours and 5-FU IV bolus followed by a continuous infusion over 22 hours on days 1, 2, 15, 16, 29, 30, 43, and 44. For both regimens, courses repeat every 8 weeks in the absence of disease progression or unacceptable toxicity. Patients are followed for tumor response and survival. PROJECTED ACCRUAL: Various NCI-designated Clinical Cancer Centers and other medical institutions across the United States will participate in this study. A total of 35-125 patients will be accrued for this study within 3 months.

Official Title
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A Multicenter Study of the Anti-VEGF Monoclonal Antibody Bevacizumab (Avastin®) Plus 5-Fluorouracil/Leucovorin in Patients With Metastatic Colorectal Cancers That Have Progressed After Standard Chemotherapy

Conditions
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Colorectal Cancer

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


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed colorectal adenocarcinoma Stage IV (metastatic) disease Not curable by surgery or radiotherapy Must have received prior standard chemotherapy regimens, including oxaliplatin and irinotecan, and meet both of the following criteria: Disease progression during or after irinotecan-based chemotherapy for metastatic disease OR relapsed disease within 6 months after adjuvant irinotecan-based therapy Disease progression during or after oxaliplatin-based chemotherapy for metastatic disease OR relapsed disease within 6 months after adjuvant oxaliplatin-based therapy No brain metastases PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 OR Karnofsky 60-100% Life expectancy Not specified Hematopoietic Absolute granulocyte count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 9 g/dL (transfusion allowed) No evidence of bleeding diathesis or coagulopathy Hepatic Bilirubin no greater than 1.5 mg/dL AST less than 5 times upper limit of normal (ULN) Alkaline phosphatase less than 5 times ULN PT and INR no greater than 1.5 times ULN PTT no greater than ULN Renal Creatinine no greater than 1.5 times ULN Proteinuria less than grade 1 OR Proteinuria less than 500 mg/24 hours Cardiovascular No prior stroke No uncontrolled high blood pressure No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia No myocardial infarction within the past 6 months No New York Heart Association class III or IV heart disease No thromboembolism within the past 6 months Other Chemonaive Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for at least 3 months after study participation No significant traumatic injury within the past 6 weeks No prior allergic reaction attributed to compounds of similar chemical or biological composition to bevacizumab or other study agents No active infection No psychiatric illness or social situation that would preclude study compliance No serious nonhealing wound (including wounds healing by secondary intention), ulcer, or bone fracture No CNS disease, including either of the following: Primary brain tumor Seizures not controlled with standard medical therapy PRIOR CONCURRENT THERAPY: Biologic therapy At least 8 weeks since prior monoclonal antibody therapy No prior bevacizumab Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy At least 4 weeks since prior major radiotherapy (e.g., chest or bone palliative radiotherapy) Surgery More than 6 weeks since prior major surgical procedure or open biopsy More than 7 days since prior fine needle aspiration or core biopsy No concurrent surgery Other Recovered from prior therapy At least 3 weeks since prior cytotoxic agents No concurrent therapeutic anticoagulation Prophylactic anticoagulation of venous access devices allowed provided PT/INR or PTT criteria are met No concurrent chronic aspirin (greater than 325 mg/day) or nonsteroidal anti-inflammatory drugs No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational or commercial agents for the malignancy

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: bevacizumab|nan|
|Drug: fluorouracil|nan|
|Drug: leucovorin calcium|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 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 rectal cancer, recurrent rectal cancer, stage IV colon cancer, recurrent colon cancer