Clinical Trial: Acetylsalicylic Acid and Eflornithine in Treating Patients at High Risk for Colorectal Cancer

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Randomized Phase II Trial of Aspirin and Difluoromethylornithine (DFMO) in Patients at High Risk of Colorectal Cancer

Brief Summary: This phase II trial is studying how well giving acetylsalicylic acid together with eflornithine works in treating patients at high risk for colorectal cancer. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of acetylsalicylic acid and eflornithine may prevent colorectal cancer.

Detailed Summary:

PRIMARY OBJECTIVES:

I. The proportion of subjects with an adenoma recurrence at the 1-year follow-up colonoscopy exam. This adenoma recurrence rate for difluoromethylornithine (DFMO) (eflornithine) + aspirin will be compared to double placebo to see if there is improvement in the adenoma recurrence rate in this patient population.

SECONDARY OBJECTIVES:

I. To determine the relative tolerability and safety of the treatment regimens administered for 12 months.

II. To determine the effect of the study drugs (aspirin [acetylsalicylic acid] + DFMO) and placebo with respect to proliferation (Ki67 labeling index), apoptosis (caspase-3 expression assay), and drug effect markers (COX-1, -2, polyamines, PGE2) from adenomas, aberrant crypt focus (ACF) and normal-appearing mucosa using pre- and 12-month post-intervention tissue biopsy samples.

III. To estimate the percentage change in rectal ACF number, as determined by magnifying colonoscopy in subjects treated for 12 months with placebo or study drugs (aspirin +DFMO) by comparing % change in drug versus placebo arms.

IV. To characterize ACF based on three criteria (ACF size [crypt number < 50 or >= 50], crypt morphology characteristics, and histology) of ACF and to correlate such characteristics with the intervention (vs placebo). Also, to evaluate the natural history of ACF over 1-year on placebo.

V. To correlate the 12-month measurements of ACF size (# crypts/ACF), number, morphology, and histopathology with the adenoma recurrence data at 12 and 36 months; correlate the 12-month % (and actual) change in ACF size and number with th
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Adenoma recurrence rate for the treatment arm relative to placebo [ Time Frame: At 1 year ]

Original Primary Outcome: Adenoma recurrence rate for the treatment arm relative to placebo [ Time Frame: 1 year ]

Current Secondary Outcome:

• ACF characteristics vs adenoma recurrence rate [ Time Frame: 12 months ]
  ACF analysis will only be conducted in those participants who have at least 5 rectal ACF at baseline.
• Characterization of ACF [ Time Frame: 1 year ]
  Based on four criteria and correlate such characterizations with the intervention (vs. placebo), as well as exploring the natural history of ACF.
• Comparison of the percent change in ACF number across the 2 treatment arms [ Time Frame: At 12 months ]
  Calculated as the number of ACF present at the 12-month post-intervention exam minus the baseline number of ACF, divided by the number of ACF present at baseline.
• Effect of the study drugs and placebo with respect to biomarkers [ Time Frame: Baseline and 12 months ]
  For continuous variables, we will use the 2-sample t-test (or nonparametric equivalent) to compare the active arm to the placebo arm. For categorical data, we will explore the relationship between the treatment arms and biomarkers with chi-square or fisher's exact tests. Correlations will be sought between caspase-3 staining, proliferative indices and their ratio, as well as other biomarkers using a chi-square test.
• Gene expression analysis [ Time Frame: Baseline and 12 months ]
  Differences in log-transformed values among ACF or patient characteristics will be compared using t tests or analysis of variance (ANOVAs). P < 0.05 was considered statistically significant.
• Safety, tolerability, and adverse events of study treatment [ Time Frame: Up to 48 months ]
  Reviewed via frequency tables and univariate statistics. Chi-square tests will be used to explore the relationship between tolerability and intervention, for categorical data. To evaluate the adverse event profile associated with the intervention arm, the maximum grade for each type of adverse event will be recorded for each subject, and frequency tables will be reviewed to determine the overall patterns. The National Cancer Institute (NCI) Common Terminology Criteria (CTC) Version 3.0 will be used to grade all adverse events.

Original Secondary Outcome:

• Comparison of the percent change in ACF number across the 2 treatment arms
• Characterization of ACF (correlative study)
• Exploratory analyses of biomarkers (correlative study)
• Summarizing all adverse events that occur across both arms (correlative study)
• Exploratory analyses of ACF characteristics vs adenoma recurrence rate (correlative study)
• Gene expression analysis (optional correlative study)

Dates:
Date Received: September 23, 2009
Date Started: August 2009
Date Completion:
Last Updated: October 14, 2016
Last Verified: October 2016