Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the colon

  • Stage II disease (pT3, pT4a-b, N0, M0)

    • At least 8 lymph nodes must have been evaluated

• Meets 1 of the following criteria:

  • High risk for microsatellite instability (MSI) and loss of heterozygosity (LOH) at chromosome 18q

    • Microsatellite stable (MSS) with 18q LOH
    • MSI-low grade (MSI-L) with 18q LOH

  • Low risk for MSI and 18q LOH

    • MSS with retention of 18q alleles
    • MSI-L with retention of 18q alleles
    • MSI-high grade (MSI-H) with retention of 18q alleles
    • MSI-H without retention of 18q alleles
    • MSI-H with 18q status uninformative

• Distal extent of tumor must be ≥ 12 cm from the anal verge by endoscopy or surgical examination

  • If tumor is located beyond sigmoid colon and centimeter distance is unavailable, include anatomic region of the colon (e.g., right colon, transverse colon, hepatic flexure, descending colon, or cecum)

• Has undergone surgical resection of the tumor between the past 28-60 days

  • Must have had a complete resection (R0 resection)
• No history of isolated, distant, or noncontiguous intra-abdominal metastases
• Patients with synchronous tumors or appendiceal tumors are ineligible
• Hereditary non-polyposis colorectal cancer allowed
• Paraffin-embedded tumor specimen (one with normal mucosa and one from the resection tumor) available
• Performance status - ECOG 0-2
• Absolute granulocyte count ≥ 1,500/mm^3*
• Platelet count ≥ 100,000/mm^3*
• No significant bleeding unrelated to tumor within the past 6 months*
• Bilirubin normal (unless due to Gilbert's disease or similar syndrome)*
• Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN)*
• AST < 1.5 times ULN*

• PT INR > 1.5* allowed provided the following criteria are met:

  • Patient is on full-dose anticoagulants
  • INR in range (usually 2-3) on a stable dose of warfarin or low molecular weight heparin
  • No active bleeding or pathological condition associated with a high risk of bleeding unrelated to primary colon tumor
• No systemic hepatic disease*
• Creatinine ≤ 1.5 times ULN*
• Urine protein:creatinine ratio < 1.0*
• Urine protein < 1 gm on 24-hour urine collection*
• No systemic renal disease*
• History of hypertension allowed provided blood pressure < 150/90 mm Hg while on a stable regimen of anti-hypertensive therapy*
• No New York Heart Association class III or IV cardiac disease*
• No symptomatic arrhythmia*
• No history of transient ischemic attack*
• No history of cerebrovascular accident*
• No symptomatic peripheral vascular disease*
• No arterial thromboembolic events within the past 12 months*
• No unstable angina within the past 12 months*
• No myocardial infarction within the past 12 months*
• No other systemic cardiovascular disease*
• Not pregnant or nursing*
• Negative pregnancy test*
• Fertile patients must use effective contraception during and for 3 months after completion of study treatment*
• No active gastroduodenal ulcer by endoscopy*
• No complete obstruction or perforation of the bowel
• No history of inflammatory bowel disease
• No prior or concurrent malignancy except for nonmelanoma skin cancer, carcinoma in situ of the cervix, breast cancer in situ, treated non-pelvic cancer from which the patient has been disease-free for > 5 years, or history of breast cancer (without evidence of disease) and remain on hormonal therapy for > 5 years
• No other nonmalignant systemic disease that would preclude study compliance*
• No psychiatric or addictive disorder or other condition that would preclude study participation*
• No serious or non-healing wound, skin ulcer, or bone fracture*
• No peripheral neuropathy ≥ grade 2*
• No significant traumatic injury within the past 4 weeks*
• No known allergy to platinum compounds
• No prior radiotherapy for this cancer
• No prior systemic therapy for this cancer
• More than 28 days since prior major surgery or open biopsy*
• More than 7 days since prior core biopsy or other minor procedure except placement of a vascular access device*