Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps
This randomized phase III trial is studying eflornithine and sulindac to see how well they work compared to a placebo in preventing colorectal cancer in patients with colon polyps. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eflornithine and sulindac may prevent colorectal cancer. It is not yet known whether eflornithine and sulindac are more effective than a placebo in preventing colorectal cancer
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
|Official Title:||A Phase III Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Combination of DFMO and Sulindac to Decrease the Rate of Recurrence of Adenomatous Polyps in the Colon|
- Rate of new adenomatous polyp formation [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]Fisher's exact test will be used to compare treatment groups with regard to the proportions of patients with at least one new adenoma. Ninety-five percent confidence intervals for the proportion of recurrent adenomas will be computed for each treatment group. For multivariate analyses, logistic regression will be used to model the presence of at least one adenoma.
- Changes in measurements of colorectal tissue polyamine and prostaglandin E2 measurements [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]The average proportionate change from baseline in each treatment group, logarithmically transformed to reduce skewness, will be compared using the paired t-test (time 0 to time 36). Logistic regression will be used to model the proportion of interval incident adenomas.
- Rate of side effects experienced by patients [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]Mutually exclusive categories, "no side effects" versus "side effects of grade 1 or higher" will be compared with regard to treatment groups using Fisher's exact test.
|Study Start Date:||July 1998|
|Primary Completion Date:||August 2008 (Final data collection date for primary outcome measure)|
Placebo Comparator: Arm I (placebo)
Patients receive oral double placebo once daily.
Other Name: PLCBOther: laboratory biomarker analysis
Experimental: Arm II (eflornithine and sulindac)
Patients receive oral eflornithine (DFMO) and oral sulindac once daily. In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.
Other Names:Drug: sulindac
Other Names:Other: laboratory biomarker analysis
I. Compare the rate of new adenomatous polyp formation in patients with a history of adenomatous polyps of the colon treated with eflornithine and sulindac vs placebo.
II. Correlate the effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa with the rate of new adenoma formation in these patients.
III. Compare the rate of side effects in patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to participating center and aspirin use (yes vs no).
Patients receive oral double placebo once daily for 4 weeks. Patients who are more than 70% compliant by pill measurement or self reporting are randomized to 1 of 2 treatment arms.
Arm I: Patients receive oral double placebo once daily.
Arm II: Patients receive oral eflornithine (DFMO) and oral sulindac once daily.
In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.
|United States, California|
|University of California Medical Center At Irvine-Orange Campus|
|Orange, California, United States, 92868|
|Principal Investigator:||Frank Meyskens||University of California Medical Center At Irvine-Orange Campus|