Clinical Trial: Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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

Detailed Summary:

PRIMARY OBJECTIVES:

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.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Detection of Any Adenoma at the End of the Study [ Time Frame: Up to 36 months ]

Detection of any adenoma at the end of the study. This analysis is based on the participants who had the end-of-study colonscopy procedure done.


Original Primary Outcome:

Current Secondary Outcome:

  • Detection of Any Adenoma at the End of the Study Stratified by Baseline Prostaglandin E2 (PGE2) and Treatment [ Time Frame: Up to 36 months ]
    This analysis is based on the participants who had the end-of-study colonscopy procedure done and their baseline PGE2 values are available. The low PGE2 is defined as the values that are below the median PGE2 value in the analysis cohort. The high PGE2 is defined as the values that are above the median PGE2 value in the analysis cohort.
  • Detection of Any Adenoma at the End of the Study Stratified by Baseline Putrescine and Treatment [ Time Frame: Up 36 months ]
    The low is defined as the values that are below the median putrescine level in the analysis cohort. The high is defined as the values that are above the median putrescine level in the analysis cohort.
  • Detection of Any Adenoma at the End of the Study Stratified by Baseline Spermidine-to-spermine Ratio and Treatment [ Time Frame: Up 36 months ]

    The low is defined as the ratios that are below the median spermidine-to-spermine ratio in the analysis cohort. The high is defined as the ratios that are above the median spermidine-to-spermine ratio in the analysis cohort.

    In the finalized datasaet, the total number of adnoma detected in the placebo group is 55. The descrepancy in the total number of adnoma detected in placebo group between Outcome Measure 1 and this oucome is due to the revolution of the datatset.

    The analysis cohort is based on the participants whose data are available and complete.

  • Detection of Any Adenoma at the End of the Study Stratified by Prostaglandin E2 (PGE2) Response and Treatment [ Time Frame: Up to 36 months ]
    PGE2 Responder = PGE2 values at 36-month are decreased by >=30% in PGE2 values from baseline PGE2 nonresponder = PGE2 values at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
  • Detection of Any Adenoma at the End of the Study Stratified by Putrescine Response and Treatment [ Time Frame: Up to 36 months ]
    Putrescine responder = Putrescine values at 36-month are decreased by >=30% from baseline Putrescine nonresponder = Putrescine values at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
  • Detection of Any Adenoma at the End of the Study Stratified by Spermidine-to-spermine Ratio Response and Treatment [ Time Frame: Up to 36 months ]
    Spermidine-to-spermine ratio responder = ratios at 36-month are decreased by >=30% from baseline Spermidine-to-spermine ratio nonresponder = ratios at 36-month are increased, or decreased by < 30% from baseline The analysis cohort is based on the participants whose data are available and complete.
  • Adverse Events With a Grade of 3 and Above [ Time Frame: Up to 36 months ]

    Participants reported at least 1 adverse event with a grade of 3 and above, regardless if the event is defined as serious per protocol or other.

    Per protocol, not all grade 3 events are considered as serious events.

  • Baseline Putrescine by ODC Genotype [ Time Frame: Baseline ]
    ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
  • Baseline Spermidine by ODC Genotype [ Time Frame: Baseline ]
    ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
  • Baseline Spermine by ODC Genotype [ Time Frame: Baseline ]
    ODC genotype is the genotype of single nucleotide polymorphisms (SNP) in the ornithine decarboxylase (ODC) promoter The analysis cohort is based on the participants whose data are available and complete.
  • At the End of the Study - Putrescine Response by ODC Genotype [ Time Frame: At the end of the study ]

    Putrescine responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) ≥ the threshold. Putrescine non-responder was defined as (tissue putrescine value at baseline - tissue putrescine value at the end of the study)/(tissue putrescine value at baseline) < the threshold. The thresholds range from 0.25 to 0.45 with an increment of 0.5. The below data are shown for the threshold of 0.30.