Exisulind in Preventing Polyps in Patients With Familial Adenomatous Polyposis

Chemoprevention of Duodenal Polyps in Familial Adenomatous Polyposis

RATIONALE: Exisulind may be effective in preventing the development and growth of polyps in patients who have familial adenomatous polyposis.

PURPOSE: Randomized phase II/III trial to determine the effectiveness of exisulind in preventing the development and growth of polyps in patients who have familial adenomatous polyposis.

Study Overview

• Status: Withdrawn
• Conditions: Colorectal Cancer; Small Intestine Cancer
• Intervention / Treatment: Drug: exisulind

Detailed Description

OBJECTIVES:

• Determine the ability of exisulind to inhibit growth and development of duodenal adenomas in patients with familial adenomatous polyposis.
• Determine the effect on apoptosis in polyp vs mucosal tissue in these patients when treated with this drug.

OUTLINE: This is a randomized, double-blind, placebo-controlled study. Patients are randomized to one of two treatment arms.

• Arm I: Patients receive oral exisulind 4 times daily.
• Arm II: Patients receive oral placebo 4 times daily. Treatment continues for 1 year.

PROJECTED ACCRUAL: A total of 100 patients (50 per treatment arm) will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• One of the following diagnosis:

  • Diagnosis of familial adenomatous polyposis

    • Prior total or subtotal colectomy

  • Attenuated adenomatous polyposis coli

    • May have colon intact
• 10-40 duodenal polyps from second portion to 10 cm distal to papilla of Vater

PATIENT CHARACTERISTICS:

Age:

• 18 to 80

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Hemoglobin at least 10 g/dL
• Platelet count at least 100,000/mm^3
• No active hematologic disease

Hepatic:

• AST and ALT less than 1.5 times upper limit of normal (ULN)
• Alkaline phosphatase less than 1.5 times ULN
• No active hepatic disease

Renal:

• Creatinine less than 1.5 mg/dL
• No active renal disease

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active peptic ulcer disease
• No serious underlying medical or psychiatric illness that would preclude completion of the study or limit survival
• No prisoners or institutionalized patients
• No known allergy to sulindac or related compounds
• No active internal malignancy within the past 5 years
• No alcohol or drug abuse within the past 5 years

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• See Disease Characteristics

Other:

• No prior non-steroidal anti-inflammatory drugs (NSAIDs) or salicylates more than 10 days a month for the past 3 months
• No concurrent NSAIDs (e.g., mesalamine, olsalazine, azodisalicylate, salsalate, sulfasalazine)
• Aspirin for cardiac reasons allowed (81 mg/day or 325 mg twice/week)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Double

Collaborators and Investigators

• Sponsor: University of Utah
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: James A. DiSario, MD, University of Utah

Study record dates

Study Major Dates

• Study Start: July 1, 1999
• Primary Completion (Actual): July 1, 1999
• Study Completion (Actual): July 1, 1999

Study Registration Dates

• First Submitted: November 9, 2001
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): July 24, 2013
• Last Update Submitted That Met QC Criteria: July 23, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: rectal cancer; colon cancer; small intestine cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Genetic Diseases, Inborn; Colonic Diseases; Intestinal Diseases; Colorectal Neoplasms; Neoplastic Syndromes, Hereditary; Adenomatous Polyps; Adenoma; Intestinal Polyposis; Adenomatous Polyposis Coli; Intestinal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Protective Agents; Anticarcinogenic Agents; Sulindac sulfone
• Other Study ID Numbers: CDR0000069032; P30CA042014 (U.S. NIH Grant/Contract); R01CA080852 (U.S. NIH Grant/Contract); UUMC-IRB-5999-96; NCI-H01-0079