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

Inclusion 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