A Double Blind Placebo-Controlled Trial of Eflornithine and Sulindac to Prevent Recurrence of High Risk Adenomas and Second Primary Colorectal Cancers in Patients with Stage 0-III Colon or Rectal Cancer, Phase III - Preventing Adenomas of the Colon with Eflornithine and Sulindac (PACES)"

History of Stage 0, I, II or III colon or rectal cancer; patients must be registered between 120 days and 465 days (inclusive) of primary resection; patients must show no evidence of colorectal cancer based on post-op colonoscopy (performed at least 120 days after the colon or rectal resection date and prior to registration); patients must not have cardiovascular risk factors including unstable angina, history of documented myocardial infarction or cerebrovascular accident, coronary artery bypass surgery or NY Hear Assoc. Class III or IV heart failure; Patients must not have uncontrolled hyperlipidemia (defined as LDL-C >/= 190 mg/dL or triglycerides >/= 500 mg/dL) within the past 3 years prior to registration or uncontrolled high blood pressure (systolic blood pressure > 150 mm Hg) within 28 days prior to registration; adjuvant chemo and RT treatment must have been completed at least 30 days prior to registration; patients must not have a known history of familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, or inflammatory bowel disease, biallelic mismatch repair deficiency syndrome, or constitutional mismatch repair deficiency syndrome; patients with a personal history of large bowel resection > 40 cm are not eligible; patients must not have known hypersensitivity to eflornithine or sulindac; patients must not have documented history of gastric/duodenal ulcer within the last 12 months; patients with gastroesophageal reflux disease are eligible if controlled with medications; patients must have Zubrod PS of 0-1; patients must not be expecting to receive RT or additional chemotherapy; patients must not be receiving or plan to receive concomitant oral or intravenous corticosteroids on a regular basis, nonsteroidal anti-inflammatory drugs (NSAIDs), nor anticoagulants on a regular or predictable intermittent basis; maximum aspirin dose </=100 mg per day or </= two 325 mg tablets per week; inhaled steroids (ie. for asthma or related conditions) are allowed; able to swallow oral medications; Laboratory: WBC >/= 4.0 x 1000/mcL, platelets >/= 100,000/mcL and hemoglobin > 11.0 g/dL; a total WBC >/= 3.1 x 103/mcL is allowed for non-hispanic black males (NHBM) and total WBC >/= 3.4 x 103/mcL for non-hispanic black females (NHBF); serum bilirubin </= 2.0 mg/dL and AST (SGOT) or ALT (SGPT) </= 2 x IULN, Serum creatinine </= 1.5 x IULN;patients must be 18 years of age or older;CEA for patients who had T2 or greater tumors; will not participate in any other clinical trial for the treatment or prevention of cancer unless off protocol treatment, on follow-up phase only; offered opportunity to participate in blood specimen banking. After this criteria is met, patients must have pure tone audiomety evaluation to document air conduction within 30 days prior to registration.