RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. It is not yet known whether sulindac, aspirin, or ursodiol is more effective in preventing colorectal cancer.

PURPOSE: Randomized phase II trial to compare the effectiveness of sulindac, aspirin, and ursodiol in preventing colorectal cancer.

Condition	Treatment or Intervention	Phase
Colorectal Cancer stage I colon cancer stage II colon cancer stage III colon cancer stage IV colon cancer	Drug: aspirin  Drug: sulindac  Drug: ursodiol  Procedure: biological response modifier therapy  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: prostaglandin inhibition	Phase II

Further Study Details: 

OBJECTIVES:

• Determine the percentage change in colorectal aberrant crypt foci (ACF) in patients with a history of colorectal cancer or at high risk for colorectal cancer when treated with sulindac vs aspirin vs ursodiol.
• Determine the safety and efficacy of these drugs, in terms of ability to cause regression of existing colorectal ACF and prevent new ACF development, in these patients.

OUTLINE: This is a partially blinded, randomized, placebo-controlled study. Patients are stratified according to colorectal neoplasia (adenoma vs carcinoma). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive oral sulindac twice daily.
• Arm II: Patients receive oral aspirin once daily.
• Arm III: Patients receive oral ursodiol three times daily.
• Arm IV: Patients receive oral sulindac placebo twice daily. In all arms, treatment continues for 12 months in the absence of disease progression or unacceptable toxicity.

Patients undergo a colonoscopy at baseline and at the end of treatment.

Patients are followed at 2 months after the end of treatment.

PROJECTED ACCRUAL: A total of 172 patients (43 per treatment arm) with a history of colorectal cancer or adenomas will be accrued for this study. A total of 20 additional patients with no elevated risk of colorectal neoplasia will be accrued, but not randomized, for this study.

Ages Eligible for Study:  40 Years   -   80 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Presence of at least 5 colorectal aberrant crypt foci
• Meets 1 of the following criteria:
• Recent or current history of colorectal cancer* defined by 1 of the following:
• Dukes' A/B1 carcinoma within the past 5 years
• Any stage of colorectal cancer if at least 5 years after surgical resection NOTE: *No rectal cancer except for transanal excision without radiotherapy
• Recent or current history of colorectal adenoma(s) defined by 1 of the following:
• One adenomatous polyp at least 1 cm
• Two or more adenomatous polyps of any size
• One adenomatous polyp of any size and a documented history of prior adenomatous polyps
• No elevated risk of colorectal cancer or adenoma
• No known familial adenomatous polyposis
• No hereditary nonpolyposis colon cancer
• No inflammatory bowel disease

PATIENT CHARACTERISTICS: Age

• 40 to 80

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• WBC greater than 3,000/mm^3
• Platelet count greater than 100,000/mm^3
• Hemoglobin greater than 10.0 g/dL
• No bleeding diathesis

Hepatic

• Bilirubin no greater than 1.5 mg/dL
• AST and ALT less than 2 times upper limit of normal
• No unexplained elevation of transaminases
• No acute liver disease

Renal

• No history of renal stones

Pulmonary

• No asthma

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to participate in scheduled follow-up tests
• No history of gastroduodenal ulcers by endoscopy
• No history of hypersensitivity to cyclo-oxygenase-2 inhibitors, sulfonamides, NSAIDs, salicylates, or ursodiol
• No hypersensitivity to sulindac products
• No significant medical or psychiatric problem that would preclude study participation
• No other invasive carcinoma within the past 5 years except Dukes' A/B1 carcinoma or any stage of colorectal cancer that is at least 5 years post-surgical resection
• No "unacceptable clinical risk" to proceed including:
• New diagnosis of carcinoma
• Suspicion of need for colectomy

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• More than 6 months since prior chemotherapy
• Topical chemotherapy may be allowed on a case-by-case basis

Endocrine therapy

• At least 30 days since prior nasal steroids
• No concurrent nasal steroids (mometasone allowed)
• No concurrent oral corticosteroids

Radiotherapy

• No prior radiotherapy to the pelvis or rectum

Surgery

• See Disease Characteristics
• No prior colectomy

Other

• More than 3 months since prior investigational agents
• At least 3 months since prior nonsteroidal anti-inflammatory drugs (NSAIDs) (including aspirin)
• Concurrent acetaminophen allowed
• No concurrent aspirin (including as a cardioprotectant)
• No concurrent NSAIDs (e.g., ibuprofen or naproxen)

Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030-4009,  United States; Recruiting

Study chairs or principal investigators

Robert S. Bresalier, MD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000304433; MDA-ID-01454; NCT00062023
Record last reviewed:  June 2003
Last Updated:  February 7, 2005
Record first received:  June 5, 2003
ClinicalTrials.gov Identifier:  NCT00062023
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08