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

• Status: Completed
• Trial end date: 2007-07-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Bevacizumab; Calcium; Fluorouracil; Leucovorin; Levoleucovorin

Criteria

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