Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced, recurrent, or metastatic colorectal adenocarcinoma

• Not curable by surgery or amenable to radiotherapy with curative intent

• Previously resected colorectal cancer with new evidence of metastasis does not require separate histologic or cytologic confirmation unless one of the following is true:

• More than 5 years has elapsed between primary surgery and development of metastatic disease

• Primary tumor was T1-T2, N0, M0

• Site of primary lesion must be or have been in the large bowel as determined by endoscopy, radiology, or surgery

• Measurable or evaluable disease

• No known brain or leptomeningeal disease

• Performance status - Zubrod 0-2

• No history of hemorrhagic or thrombotic disorders

• Absolute neutrophil count greater than 1,500/mm^3

• Platelet count greater than 100,000/mm^3

• Bilirubin no greater than 2.0 times upper limit of normal (ULN)

• SGOT no greater than 2.5 times ULN (5 times ULN for patients with liver involvement)

• Alkaline phosphatase no greater than 2.5 times ULN (5 times ULN for patients with liver involvement or 10 times ULN for patients with bone involvement)

• INR no greater than 1.5

• PTT no greater than ULN

• Creatinine no greater than 1.5 times ULN

• Creatinine clearance at least 50 mL/min

• Proteinuria less than 1+*

• Protein less than 500mg/24 hours*

• No uncontrolled hypertension

• Hypertension must be well-controlled (i.e., less than 160/90) and on a stable regimen of antihypertensive therapy

• No unstable angina

• No symptomatic congestive heart failure

• No myocardial infarction within the past 6 months

• No serious uncontrolled cardiac arrhythmia

• No New York Heart Association class III or IV heart disease

• No symptomatic pulmonary fibrosis

• Not pregnant or nursing

• Fertile patients must use effective contraception

• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

• No active or uncontrolled severe infection

• No contraindication to oral medications (e.g., severe dysphagia)

• G-tubes or J-tubes allowed

• No peripheral neuropathy greater than grade 1

• No serious non-healing wound, ulcer, or bone fracture

• No significant traumatic injury within the past 28 days

• No other severe acute or chronic medical condition or laboratory abnormality that would preclude study participation

• No psychiatric condition that would preclude study participation

• No prior bevacizumab

• No prior oxaliplatin

• No prior chemotherapy for advanced colorectal cancer

• Prior adjuvant therapy for resected stage II-III disease allowed provided at least 12 months have elapsed between completion of therapy and diagnosis of recurrent disease

• At least 28 days since prior radiotherapy and recovered

• See Disease Characteristics

• More than 28 days since prior major surgical procedure or open biopsy

• More than 7 days since prior fine needle aspiration or core biopsy

• No concurrent major surgery

• More than 10 days since prior full-dose aspirin (325 mg)

• No concurrent antiplatelet agents (e.g., dipyridamole, ticlopidine, clopidogrel, or cilostazol)

• No other concurrent investigational agents

• No concurrent therapeutic anticoagulation

• Prophylactic anticoagulation of central venous lines allowed

• Low-dose prophylactic enoxaparin or heparin allowed

• No concurrent cimetidine

• No concurrent sorivudine or its related analogs (e.g., brivudine)

• No concurrent use of a cold cap or iced mouth rinses