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

Inclusion Criteria:

• Patients must consent to be in the study and must have signed and dated an IRBapproved consent form conforming to federal and institutional guidelines

• Randomization must occur during the three-week interval beginning on postoperative day 29 and ending on postoperative day 50

• The distal extent of the tumor must be >= 12 cm from the anal verge on endoscopy; ifthe patient is not a candidate for endoscopy, then the distal extent of the tumor mustbe >= 12 cm from the anal verge as determined by surgical examination

• The patient must have had an en bloc complete gross resection of tumor (curativeresection) by open laparotomy or laparoscopically-assisted colectomy; patients whohave had a two-stage surgical procedure, to first provide a decompressive colostomyand then in a later procedure to have the definitive surgical resection, are eligible

• Patients must have histologically confirmed adenocarcinoma of the colon that meets oneof the criteria below:

• Stage II carcinoma (T3,4 N0 M0); the tumor invades through the muscularis propriainto the subserosa or into non-peritonealized pericolic or perirectal tissues (T3); or directly invades other organs or structures, and/or perforates visceralperitoneum (T4)

• Stage III carcinoma (any T N1,2 M0); the tumor has invaded to any depth, withinvolvement of regional lymph nodes

• Patients with T4 tumors that have involved an adjacent structure (e.g., bladder, smallintestine, ovary, etc.) by direct extension from the primary tumor are eligible if allof the following conditions are met:

• All or a portion of the adjacent structure was removed en bloc with the primarytumor

• In the opinion of the surgeon, all grossly visible tumor was completely resected ("curative resection")

• Histologic evaluation by the pathologist confirms the margins of the resectedspecimen are not involved by malignant cells; and

• Local radiation therapy will not be utilized

• Patients with more than one synchronous primary colon tumor are eligible; (stagingclassification will be based on the more advanced primary tumor)

• Patients must have an ECOG performance status of 0 or 1

• At the time of randomization, postoperative absolute granulocyte count (AGC) must be >= 1500/mm^3 (or < 1500/mm^3, if in the opinion of the investigator, this representsan ethnic or racial variation of normal)

• At the time of randomization, the postoperative platelet count must be >= 100,000/mm^3

• Bilirubin must be =< ULN for the lab unless the patient has a chronic grade 1bilirubin elevation due to Gilbert's disease or similar syndrome due to slowconjugation of bilirubin

• Alkaline phosphatase must be < 2.5 x ULN for the lab

• AST must be < 1.5 x ULN for the lab

• If AST is > ULN, serologic testing for hepatitis B and C must be performed andresults must be negative

• Serum creatinine =< 1.5 x ULN for the lab

• Urine protein/creatinine (UPC) ratio of < 1.0; patients with a UPC ratio >= 1.0 mustundergo a 24-hour urine collection, which must be an adequate collection and mustdemonstrate < 1 gm of protein in the 24-hour urine collection in order to participatein the study

• Patients with prior malignancies, including colorectal cancers, are eligible if theyhave been disease-free for >= 5 years and are deemed by their physician to be at lowrisk for recurrence; patients with squamous or basal cell carcinoma of the skin,melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colonor rectum that have been effectively treated are eligible, even if these conditionswere diagnosed within 5 years prior to randomization

Exclusion Criteria:

• Patients < 18 years old

• Colon tumor other than adenocarcinoma, i.e., sarcoma, lymphoma, carcinoid, etc

• Rectal tumors, i.e. a tumor located < 12 cm from the anal verge on endoscopy, or bysurgical exam if the patient is not a candidate for endoscopy

• Isolated, distant, or non-contiguous intra-abdominal metastases, even if resected

• Any systemic or radiation therapy initiated for this malignancy

• Any significant bleeding that is not related to the primary colon tumor within 6months before study entry

• Serious or non-healing wound, skin ulcers, or bone fracture

• Gastroduodenal ulcer(s) determined by endoscopy to be active

• Invasive procedures defined as follows:

• Major surgical procedure, open biopsy, or significant traumatic injury within 28days prior to randomization

• Anticipation of need for major surgical procedures during the course of the study

• Core biopsy or other minor procedure, excluding placement of a vascular accessdevice, within 7 days prior to randomization

• Uncontrolled blood pressure defined as > 150/90 mmHg

• History of TIA or CVA

• History of arterial thrombotic event within 12 months before study entry

• Symptomatic peripheral vascular disease

• PT/INR > 1.5, unless the patient is on therapeutic doses of warfarin. If so, thefollowing criteria must be met for enrollment:

• The subject must have an in-range INR (usually between 2 and 3) on a stable doseof warfarin

• The subject must not have active bleeding or a pathological condition that isassociated with a high-risk of bleeding

• Concomitant halogenated antiviral agents

• Clinically significant peripheral neuropathy at the time of randomization (defined inthe NCI Common Terminology Criteria for Adverse Events Version 3.0 [CTCAE v3.0] asgrade 2 or greater neurosensory or neuromotor toxicity)

• Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that wouldpreclude any of the study therapy drugs; specifically excluded are the followingcardiac conditions:

• New York Heart Association Class III or IV cardiac disease

• History of myocardial infarction within 12 months before study entry

• Unstable angina within 12 months before study entry; and

• Symptomatic arrhythmia

• History of chronic or persistent viral hepatitis or other chronic liver disease

• Pregnancy or lactation at the time of proposed randomization; eligible patients ofreproductive potential (both sexes) must agree to use adequate contraceptive methodsduring study therapy and for at least 3 months after the completion of bevacizumab

• Psychiatric or addictive disorders or other conditions that, in the opinion of theinvestigator, would preclude the patient from meeting the study requirements