Second-Line Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer Who Have Received First-Line Chemotherapy and Bevacizumab

DISEASE CHARACTERISTICS:

• Histologically confirmed colorectal adenocarcinoma

  • Metastatic or unresectable disease

• Progressive disease based on the following criteria:

  • Progression during or after first-line chemotherapy for metastatic disease, including any of the following:

    • Fluoropyrimidine-based monotherapy with bevacizumab
    • Fluoropyrimidine and irinotecan hydrochloride-based doublet with bevacizumab
    • Fluoropyrimidine and oxaliplatin-based doublet with bevacizumab
  • Progression after more than 3 months from the last administration of first-line chemotherapy for metastatic disease with a fluoropyrimidine, irinotecan hydrochloride, and oxaliplatin triplet (FOLFOXIRI) with bevacizumab to which the patient had previously responded
• Measurable disease, as assessed by RECIST criteria
• No prior or concurrent CNS metastasis

PATIENT CHARACTERISTICS:

• ECOG performance status 0-2
• Life expectancy > 3 months
• ANC ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• INR ≤ 1.5 times upper limit of normal (ULN)
• aPTT ≤ 1.5 ULN
• Serum bilirubin ≤ 1.5 times ULN
• AST and ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
• Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
• Serum creatinine ≤ 1.5 times ULN
• Proteinuria < 2+ OR protein ≤ 1g by 24-hour urine
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No bowel obstruction or subobstruction
• No history of inflammatory enteropathy
• No prior extensive intestinal resection (i.e., > hemicolectomy or extensive small intestine resection with chronic diarrhea)
• No symptomatic peripheral neuropathy > grade 2
• No active uncontrolled infection
• No active disseminated intravascular coagulation
• No prior or concurrent malignancy, except for curatively treated basal cell and squamous cell carcinoma of the skin, or in situ carcinoma of the cervix

• No clinically significant cardiovascular disease, including any of the following:

  • Cerebrovascular accident within the past 6 months
  • Myocardial infarction within the past 6 months
  • Unstable angina
  • NYHA class II-IV chronic heart failure
  • Uncontrolled arrhythmia
• No uncontrolled hypertension
• No thromboembolic or hemorrhagic events within the past 6 months
• No evidence of bleeding diathesis or coagulopathy
• No serious, non healing wound/ulcer or serious bone fracture
• No significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 6 weeks since prior radiotherapy
• At least 4 weeks since prior surgery
• No prior first-line chemotherapy for metastatic disease without bevacizumab
• No prior cetuximab or other investigational agents
• More than 28 days since prior open biopsy
• More than 28 days since prior and no concurrent major surgical procedure

• No concurrent therapeutic anticoagulation, antiplatelet agents, or NSAID with anti-platelet activity

  • Acetylsalicylic acid ≤ 325 mg/day allowed