Clinical Trial: Celecoxib With or Without Eflornithine in Preventing Colorectal Cancer in Patients With Familial Adenomatous Polyposis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Two-Arm Phase II Chemoprevention Trial in Adenomatous Polyposis Coli Patients

Brief Summary: This randomized phase II trial studies how well giving celecoxib with or without eflornithine works in preventing colorectal cancer in patients with familial adenomatous polyposis. Chemoprevention is the use of certain drugs to keep cancer from forming. The use of celecoxib and eflornithine may keep cancer from forming in patients with familial adenomatous polyposis.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To determine the relative efficacy of celecoxib plus eflornithine (DFMO) versus celecoxib plus DFMO placebo in participants with familial adenomatous polyposis (FAP), as evidenced by the percent change from baseline in the number of polyps in focal area(s) of the colorectum in participants having 5 or more >= 2mm colorectal polyps with or without duodenal polyps at baseline.

II. To determine the relative tolerability and safety of celecoxib + DFMO in FAP study participants.

SECONDARY OBJECTIVES:

I. To determine the percent change in polyp size in focal area(s) of the colorectum II. To determine the change in global colorectal polyp burden III. To determine the percent change in the area of plaque-like duodenal polyps in participants presenting with duodenal disease at baseline.

IV. To analyze the effects of these agents on the following panel of mucosal biomarkers: antigen identified by monoclonal antibody Ki-67 (Ki-67), mitotic index (number and spatial distribution of mitoses), phosphorylated histone H3, cyclin-dependent kinase inhibitor 1A (p21/WAF1/Cip1), apoptosis (Terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]), apoptotic index, BCL2-associated X protein (Bax), B-cell CLL/lymphoma 2 (Bcl-2) and measurement of drug effects in colonic polyp and normal tissue cyclooxygenase (cyclooxygenase-1 [COX-1], cyclooxygenase-2 [COX-2]) protein levels, prostaglandin E2 (PGE2), ornithine decarboxylase and polyamines.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive celecoxib orally (PO) twice daily (BID) and placebo
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Percent Change in the Number of Polyps Greater Than or Equal to 2mm in Diameter in Focal Area(s) of the Colorectum [ Time Frame: Baseline up to 6 months ]

Differences between average treatment effects of two study arms tested using two-sided type I error rate of 5% in two-sample t-test. If model assumptions not met by data or transformations of data, appropriate nonparametric tests (e.g. Wilcoxon rank sums test) were used to compare treatment arms - Percent change of polyp counts from baseline to 6 months, ie [(6 months - baseline) x 100]/baseline (%). For each participant, first were matched polyps between baseline & 6 months by region and landmark and summed over all matched regions on number of polyps >2 mm to calculate total number of polyps >2 mm at baseline & 6 months, respectively. For participants refusing exit colonoscopy, 0% change entered as primary endpoint. Defined ITT All: All patients; if 6-month polyp counts missing = 0% change; ITT Measurable: All participants with baseline & 6 month polyp counts; ITT Evaluable: ITT Measurable participants who also took 80% of treatment, both overall as well as during final 60 days.


Original Primary Outcome:

Current Secondary Outcome:

  • Global Duodenal Polyp Burden [ Time Frame: Up to 2 months after completion of study treatment ]
    The two-sample t-test or its non-parametric analogue, the Wilcoxon rank sums test will be used.
  • Percent Change in Polyp Size in Focal Area(s) of the Colorectum [ Time Frame: Baseline up to 2 months after completion of study treatment ]
    The two-sample t-test or its non-parametric analogue, the Wilcoxon rank sums test will be used.
  • Change in Global Colorectal Polyp Burden [ Time Frame: Baseline up to 2 months after completion of study treatment ]
    The two-sample t-test or its non-parametric analogue, the Wilcoxon rank sums test will be used.
  • Percent Change in the Area of Plaque-like Duodenal Polyps [ Time Frame: Baseline up to 2 months after completion of study treatment ]
    The two-sample t-test or its non-parametric analogue, the Wilcoxon rank sums test will be used.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: April 9, 2002
Date Started: December 2001
Date Completion:
Last Updated: December 28, 2016
Last Verified: December 2016