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