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

Inclusion Criteria:

   - STEP 1: INITIAL REGISTRATION

   - The distal extent of the tumor must be >= 12 cm from the anal verge on endoscopy; if
   this distance was not confirmed on endoscopy pre-operatively, then the distal extent
   of the tumor must be >= 12 cm from the anal verge as determined by surgical
   examination; colonoscopy should be performed postoperatively for those unable to have
   a preoperative colonoscopy to guarantee there are no synchronous lesions; (if tumor is
   located beyond sigmoid colon and centimeter distance unavailable, include anatomic
   region of colon, e.g. right colon, transverse colon, hepatic flexure descending colon,
   cecum etc.)

   - Patients must have paraffin-embedded tumor specimen available for evaluation of
   microsatellite instability and loss of heterozygosity at 18q, to determine high risk
   versus low risk

      - High-risk patients will be randomized to treatment Arms A or B

      - Low-risk patients will be registered to Arm C for observation

         - NOTE: Every effort should be made to submit blocks (tumor and normal mucosa)
         to the Principal Coordinates Analysis (PCO) immediately; blocks CANNOT be
         accepted after day 50 (post surgery) in order to allow for molecular
         assessment

         - Specific laboratory requirements for Step 2 must be obtained within 2 weeks
         prior to Step 2 randomization

   - Patients must not have synchronous tumors

   - Patients must not have appendiceal tumors

   - Patients must not have a history of inflammatory bowel disease (IBD)

   - Patients with hereditary non-polyposis colorectal cancer (HNPCC) are eligible

   - Patients must have no history of isolated, distant, or non-contiguous intra-abdominal
   metastases, even if restricted

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

      - Stage II adenocarcinoma (pT3/pT4a/pT4b pN0 M0 according to the definitions of the
      American Joint Committee on Cancer, 7th Edition, 2010): the tumor invades through
      the muscularis propria into pericolic tissues (pT3), penetrates to the surface of
      the visceral peritoneum (pT4a), or directly invades other organs or structures
      (pT4b); patients with mesenteric tumor deposits or satellites without
      identifiable residual lymph node in the absence of lymph node involvement are now
      designated pN1c, rather than pT3; patients with such tumor deposits are not
      eligible for E5202; patients must have had a complete resection (R0 resection)

   - Patients must have >= 8 lymph nodes evaluated and reported

   - Patients must not have presented with clinical complete obstruction or perforation of
   the bowel

   - Patients must not have had any systemic or radiation therapy initiated for this
   malignancy

   - Patients must not have a previous or concurrent malignancy; exceptions are made for
   patients who meet any of the following conditions:

      - Non-melanoma skin cancer, in situ cervical cancer, or breast cancer in situ

      - Prior malignancy completely excised or removed and patient has been continuously
      disease free for > 5 years

      - Patients with completely excised or removed breast cancer and disease free > 5
      years, regardless of the continuation of hormonal therapy

      - Patients with previous radiation therapy (RT) to the pelvic region will be
      ineligible

   - Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

   - STEP 2: RANDOMIZATION (HIGH RISK PATIENTS - ARMS A AND B ONLY)

   - Within 2 weeks prior to randomization, postoperative absolute granulocyte count (AGC)
   must be >= 1500/mm^3 (or < 1500/mm^3, if in the opinion of the investigator, this
   represents an ethnic or racial variation of normal)

   - Within 2 weeks prior to randomization, the postoperative platelet count must be >=
   100,000/mm^3

   - Within 2 weeks prior to randomization, there must be postoperative evidence of
   adequate hepatic function; bilirubin must be =< upper limit of normal (ULN) unless the
   patient has a chronic grade 1 bilirubin elevation due to Gilbert's disease or similar
   syndrome due to slow conjugation of bilirubin

   - Within 2 weeks prior to randomization, there must be postoperative evidence of
   adequate hepatic function; alkaline phosphatase must be < 2.5 x ULN

   - Within 2 weeks prior to randomization, there must be postoperative evidence of
   adequate hepatic function; aspartate transaminase (AST) must be < 1.5 x ULN

   - Within 2 weeks prior to randomization, there must be postoperative evidence of
   adequate renal function; serum creatinine =< 1.5 x ULN

   - Within 2 weeks prior to randomization, there must be postoperative evidence of
   adequate renal function; urine protein/creatinine (UPC) ratio of < 1.0; patients with
   a UPC ratio >= 1.0 must undergo a 24-hour urine collection, which must be an adequate
   collection and must demonstrate < 1 gm of protein in order to participate

   - Patients with any significant bleeding that is not related to the primary colon tumor
   within 6 months prior to study entry are not eligible

   - Patients with gastroduodenal ulcer(s) determined to be active by endoscopy are not
   eligible

   - Patients with a history of hypertension must measure < 150/90 mmHg and be on a stable
   regimen of anti-hypertensive therapy

   - Patients must not have a serious or non-healing wound, skin ulcers or bone fracture

   - Patients experiencing clinically significant peripheral neuropathy at the time of step
   2 randomization (defined in the National Cancer Institute [NCI] Common Terminology
   Criteria for Adverse Events version 4.0 [CTCAE 4.0] as grade 2 or greater neurosensory
   or neuromotor toxicity) are not eligible

   - Patients must not have had invasive procedures, defined as follows:

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

      - Core biopsy or other minor procedure, excluding placement of a vascular access
      device, within 7 days prior to randomization

      - Or anticipate the need for major surgical procedure(s) during the course of the
      study

   - Patients must begin adjuvant treatment no less than 28 days and no more than 60 days
   from surgery

   - Eligible patients of reproductive potential (both sexes) must agree to use an accepted
   and effective method of contraceptive during study therapy and for at least 3 months
   after the completion of bevacizumab; women must not be pregnant or breast-feeding; all
   females of childbearing potential must have a serum pregnancy test to rule out
   pregnancy within 2 weeks prior to step 2 randomization

   - Patients with prothrombin time (PT) (international normalized ratio [INR]) > 1.5 are
   not eligible, unless the patient is on full-dose anticoagulants; if so, the following
   criteria must be met for enrollment:

      - The subject must have an in-range INR (usually between 2 and 3) on a stable dose
      of warfarin or on a stable dose of low molecular weight heparin

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

   - Patients with non-malignant systemic disease (cardiovascular, renal, hepatic, etc.)
   that would preclude any of the study therapy drugs are not eligible; specifically
   excluded are the following conditions:

      - New York Heart Association (NYHA) class III or IV congestive heart failure

      - Current symptomatic arrhythmia

      - Any non-malignant systemic disease

   - Patients with a history of transient ischemic attack (TIA) or cerebrovascular accident
   (CVA) are not eligible

   - Patients with a history of the following within twelve months of study entry are not
   eligible:

      - Arterial thromboembolic events

      - Unstable angina

      - Myocardial infarction

   - Patients with symptomatic peripheral vascular disease are not eligible

   - Patients with psychiatric or addictive disorders or other conditions that, in the
   opinion of the investigator, would preclude them from meeting the study requirements
   are not eligible

   - Patients must not have a known allergy to platinum compounds

   - STEP 2: REGISTRATION (LOW-RISK PATIENTS - ARM C)

   - Patients determined to be low risk are eligible