| Inclusion Criteria: | 1) The distal extent of the tumor must be greater than or equal to 12 cm from the anal verge on endoscopy. If the distance was not confirmed on endoscopy pre-operatively, then the distal extent of the tumor must be greater than or equal to 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
2) CONTINUATION #1: (If tumor is located beyond sigmoid colon and centimeter distance unavailable, include anatomic region of colon, eg. rt colon, transverse colon, hepatic flexure, descending colon, cecum, etc.)
3) Patients must have paraffin-embedded tumor specimens 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 PCO immediately. Blocks CANNOT be accepted after day 50 (post surgery) in order to allow for molecular assessment.
4) CONTINUATION # 3: NOTE: Specific laboratory requirements for Step 2 must be obtained within 2 weeks prior to Step 2 randomization.
5) Patients must not have synchronous tumors.
6) Patients must not have appendiceal tumors.
7) Patients must not have a history of inflammatory bowel disease (IBD).
8) Patients with hereditary non-polyposis colorectal cancer (HNPCC) are eligible.
9) Patients must have no history of isolated, distant, or non-contiguous intra-abdominal metastases, even if restricted.
10) Patients must have histologically confirmed adenocarcinoma of the colon that meets the following criteria: Stage II adenocarcinoma (pT3/pT4a/pT4bpN0 M0 according to the definitions of the American Joint Committee on Cancer, 7th Edition, 2010): The tumor invades through the miscularis propria into pericolic tissues (pT3), penetrates to the surface of the visceral peritoneum (pTa), or directly invades other organs or structures (pT4b).
11) CONTINUATION #10: 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.
12) Patients must have greater than or equal to 8 lymph nodes evaluated and reported.
13) Patients must not have presented with clinical complete obstruction or perforation of the bowel.
14) Patients must not have had any systemic or radiation therapy initiated for this malignancy.
15) Patients must not have previous or concurrent malignancy. Exception are made for patients who meet any of the following conditions 1) Nonmelanoma skin cancer, in situ cervical cancer,or breast cancer in situ 2)Prior malignancy completely excised or removed and patient has been continuously disease free for >5 years. Date of last evidence of disease:____3)Patients with completely excised or removed breast cancer and disease free > 5 years regardless of the continuation of hormonal therapy. Date of last evidence of disease:____ 4) Patients with previous RT to the pelvic region will be ineligible
16) Patients must be greater than or equal to 18 years old.
17) Patients must have ECOG perfomance status of 0-2.
18) For patients randomized to Arm A or Arm B (High Risk) only: Within 2 weeks prior to randomization, postoperative absolute granulocyte count (ACG) must be greater than or equal to 1500/mm(3) (or less than 1500/mm(3) if, in the opinion of the investigator, this represents an ethnic or racial variation of normal).
19) For patients randomized to Arm A or Arm B (High Risk) only: Within 2 weeks prior to randomization, the postoperative platelet count must be greater than or equal to 100,000/mm(3).
20) For patients randomized to Arm A or Arm B (High Risk) only: Within 2 weeks prior to randomization, there must be postoperative evidence of adequate hepatic function. Bilirubin must be less than or equal to 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. Alkaline phosphatase must be less than 2.5 x ULN. AST must be less than 1.5 x ULN.
21) For patients randomized to Arm A or Arm B (High Risk) only: Within 2 weeks prior to randomization, there must be postoperative evidence of adequate renal function. Serum creatinine must be less than or equal to 1.5 x ULN. Urine protein/creatinine (UPC) ratio of less than 1.0. Patients with a UPC ratio of greater than or equal to 1.0 must undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate less than 1 gm of protein in order to participate.)
22) For patients randomized to Arm A or Arm B (High Risk) only: Patients with a history of hypertension must measure <150/90 mmHg and be on a stable regimen of anti-hypertensive therapy.
23) For patients randomized to Arm A or Arm B (High Risk) only: Patients must not have a serious or non-healing wound, skin ulcers or bone fracture.
24) For patients randomized to Arm A or Arm B (High Risk) only: Patients must not have had invasive procedures, defined as (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).
25) For patients randomized to Arm A or Arm B (High Risk) only: Patients must begin adjuvant treatment no less than 28 days and no more than 60 days from surgery.
26) For patients randomized to Arm A or Arm B (High Risk) only: 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 because the study drugs administered may cause harm to an unborn fetus or breastfeeding child. All females of childbearing potential must have a serum pregnancy test to rule out pregnancy within 2 weeks prior to randomization.
27) For patients randomized to Arm C (Low Risk): Patients determined to be low risk are eligible. |