nitric oxide-releasing acetylsalicyclic acid in preventing colorectal cancer in patients at high risk of colorectal cancer

Conditions: Colorectal Cancer

Summary: rationale: chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. the use of nitric oxide-releasing acetylsalicyclic acid may prevent colorectal cancer. purpose: this randomized phase i trial is studying the side effects and best dose of nitric oxide-releasing acetylsalicyclic acid in preventing colorectal cancer in patients at high risk of colorectal cancer.

objectives: primary * evaluate the effects of nitric oxide-releasing acetylsalicyclic acid on aberrant cryptic foci (acf) in patients at high risk for colon cancer. secondary * determine the pharmacokinetic profile of this drug in these patients. * determine the presence or absence of acf in these patients. * determine the expression of pge2, cox-1, cox-2, nf-kb, and β-catenin in colon tissue. * determine the safety and tolerability of long-term nitric oxide-releasing acetylsalicyclic acid in these patients. outline: this is a multicenter, double-blind, randomized, placebo-controlled, parallel group study. patients are stratified according to gender and race (black vs non-hispanic white vs hispanic white vs asian). patients are randomized to 1 of 3 treatment arms. * arm i: patients receive oral nitric oxide-releasing acetylsalicyclic acid twice daily for 6 months. * arm ii: patients receive nitric oxide-releasing acetylsalicyclic acid twice daily for 6 months at a higher dose than in arm i. * arm iii: patients receive oral placebo twice daily for 6 months. patients undergo sigmoidoscopies at baseline and at the completion of study treatment. biopsies of aberrant cryptic foci (acf) and non-acf sites are collected at both sigmoidoscopies. tissue is examined for biomarkers (pge_2, cox, nf-kb, β-catenin). after completion of study treatment, patients are followed periodically. projected accrual: a total of 240 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * at risk for colorectal cancer * history of histologically proven sporadic colon adenomas or colon cancer * at least 5 aberrant cryptic foci on sigmoidoscopy * less than 20 prior cumulative adenomas and no heredity nonpolyposis colorectal cancer * no significant asymptomatic lesions on sigmoidoscopy, including any of the following: * inflammation * strictures * anorectal lesions * fistulae * vascular lesions * no adenomas or colon carcinomas on flexible sigmoidoscopy * no history of gastrointestinal (gi) cancer other than colorectal cancer * no inherited colorectal cancer syndromes patient characteristics: * no other gi mucosal epithelial diseases (e.g., barrett's esophagus, chronic or recurrent peptic ulcer disease, celiac sprue, or other disorders of nutrient absorption) * no active peptic ulcer disease * no history of inflammatory bowel disease (ulcerative colitis or crohn's disease) * no known or suspected alcohol ( \> 5 glasses of wine or beer per day), drug, or medication abuse * no quantitative or qualitative platelet or coagulation abnormalities * no personal or family history of a bleeding disorder * no uncontrolled diabetes * no uncontrolled hypertension, or chronic congestive heart failure (new york heart association class ii-iv heart disease) * no myocardial infarction, transient ischemic attack, or stroke within the past 6 months * no equilibrium disorders affecting gait or ability to stand that would preclude study participation * no involuntary change in weight (up or down) of ≥ 15% of usual body weight within the past year * creatinine ≤ 2.0 mg/dl * no chronic liver disease or pancreatitis * no allergies to aspirin * no prior severe adverse reactions to nsaids such as asthma, gi bleeding, or renal insufficiency * no institutionalized, mentally disabled patients * no prisoners * not pregnant or nursing * fertile patients must use effective contraception * negative pregnancy test prior concurrent therapy: * no concurrent antibiotic prophylaxis * more than 7 days since prior nonsteroidal anti-inflammatory drug (nsaid) treatment, including aspirin * no concurrent frequent use (\> 7 days in previous month) of nsaids, cyclooxygenase (cox)-2 inhibitors, nitrovasodilators, or oral corticosteroids * no concurrent macronutrient consumption below the 1st or above the 99th percentile of u.s. consumption * no concurrent anticoagulants, ticlopidine, and clopidogrel * more than 3 months since prior general anesthesia * more than 3 months since prior investigational agents * no concurrent nsaids, including aspirin or cox-2 inhibitors * acetaminophen allowed * no concurrent nitrovasodilating drugs * more than 3 months since prior participation in other investigational trials

Keywords: colon cancer rectal cancer