Atorvastatin Calcium, Oligofructose-Enriched Inulin, or Sulindac in Preventing Cancer in Patients at Increased Risk of Developing Colorectal Neoplasia
Condition: Colon Cancer; Precancerous Condition; Rectal Cancer
MeSH terms: Precancerous Conditions
Intervention: oligofructose-enriched inulin; sulindac; placebo; atorvastatin calcium; laboratory biomarker analysis
Intervention description: Given orally; Given orally; Given orally; Given orally; Correlative studies
Intervention MeSH terms: Sulindac; Atorvastatin; Calcium
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 85.0
Sex: All
Minimum age: 40 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial is studying atorvastatin calcium to see how well it works
      compared to oligofructose-enriched inulin, sulindac, or a placebo in preventing cancer in
      patients at increased risk of developing colorectal neoplasia. Chemoprevention is the use of
      certain drugs or substances to keep cancer from forming, growing, or coming back. The use of
      atorvastatin calcium, oligofructose-enriched inulin, or sulindac may stop cancer from forming
      in patients at increased risk of colorectal neoplasia. It is not yet known whether
      atorvastatin calcium, oligofructose-enriched inulin, or sulindac are more effective than a
      placebo in preventing cancer in patients at increased risk of developing colorectal
      neoplasia.
    

Eligibility criteria:

        Criteria:

          -  ECOG performance status 0-2

          -  Platelet count >= 100,000/mm^3

          -  Fertile patients must agree to use effective contraception

          -  No history of inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis)

          -  No invasive malignancy within the past 5 years except nonmelanoma skin cancer or
             colorectal cancer

          -  No history of endoscopically-confirmed peptic ulcer disease

          -  No history of allergic reactions attributed to compounds of similar chemical or
             biological composition to the study agents

          -  No history of chronic liver disease or unexplained persistent elevations of serum
             transaminases

          -  No history of allergic-type reactions, including asthma or urticaria, to aspirin or
             NSAIDs

          -  No uncontrolled intercurrent illness including, but not limited to, any of the
             following:

               -  Ongoing or active infection

               -  Symptomatic congestive heart failure

               -  Unstable angina pectoris

               -  Cardiac arrhythmia

               -  Psychiatric illness or social situations that would preclude study compliance

          -  At least 6 weeks since prior oral corticosteroids

          -  Creatinine =< 1.5 times ULN

          -  Creatine phosphokinase =< 1.5 times ULN

          -  Not pregnant or nursing

          -  At least 6 weeks since prior statins

          -  At increased risk for developing sporadic colorectal neoplasia, as defined by 1 of the
             following:

               -  History of colon cancer (excluding stage IV or Dukes' D tumors)

               -  Must have completed prior adjuvant therapy for colon cancer >= 12 months ago

          -  History of colorectal adenomas, meeting any of the following criteria:

               -  >= 1 cm in diameter

               -  >= 3 in total number

               -  Any component of villous morphology

               -  High-grade dysplasia

          -  At least 5 rectal aberrant cryptic foci (ACF), by magnification chromoendoscopy,
             meeting both of the following criteria:

               -  At least 5 aggregated crypts in a single grouping (maximum spacing between crypts
                  must be =< 2 times the average crypt diameter)

               -  Crypt diameter >= 1.5 times the diameter of surrounding normal crypts

          -  No history of rectal cancer, familial adenomatous polyposis, or hereditary
             nonpolyposis colorectal cancer

          -  Negative pregnancy test

          -  At least 6 months since prior and no concurrent regular use* of nonsteroidal
             anti-inflammatory drugs** (NSAIDs) or statins

          -  Concurrent aspirin at cardioprotective doses (=< 162.5 mg/day or 325 mg every other
             day) allowed

          -  No prior rectal surgery involving mucosal resection

          -  No prior pelvic radiation therapy

          -  No concurrent regular use* of cyclooxygenase-2 inhibitors

          -  No concurrent anticoagulant drugs (i.e., warfarin, heparin, clopidogrel bisulfate, or
             extended-release dipyridamole)

          -  No concurrent use of any of the following:

               -  Fibrates (e.g., gemfibrozil or fenofibrate)

               -  Cyclosporine

               -  Erythromycin or macrolide antibiotics

               -  Protease inhibitors

               -  Azole antifungals

               -  Diltiazem

               -  Verapamil

               -  Compounds containing niacin or nicotinic acid

                    -  Defined as 7 consecutive days for > 3 weeks OR > 21 days total during study
                       participation

                    -  Patients may be eligible for study treatment after discontinuing NSAIDs for
                       12 weeks, at the discretion of their health care provider

          -  No other concurrent investigational agents

          -  No planned (or likely to require) clinically indicated colonoscopy or flexible
             sigmoidoscopy during study treatment

          -  Bilirubin =< 1.5 times ULN

          -  Hemoglobin >= lower limit of normal

          -  AST =< 1.5 times upper limit of normal (ULN)

          -  Alkaline phosphatase =< 1.5 times ULN