Clinical trial NCT00033371
Conditions: Colorectal Cancer Familial Adenomatous Polyposis
Sponsor: National Cancer Institute (NCI)
Start date: 2001-12-13; Completion date: 2009-03-24
Enrollment: 205 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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 description:
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 PO daily.

ARM II: Patients receive celecoxib PO BID and eflornithine PO daily.

In both arms, treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.

After completion of just treatment, patients are followed up at 1-2 months.

Arms: arm 1: Celecoxib 400 mg orally twice daily (PO BID) and Placebo once a day. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity. arm 2: Celecoxib 400 mg PO BID and Eflornithine PO daily 0.5 g/m\^2/day rounded down to the nearest 250 mg dose. Treatment continues for 6 months in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Celecoxib intervention 2: Placebo intervention 3: eflornithine intervention 4: Laboratory biomarker analysis intervention 5: Questionnaire administration
Intervention descriptions: intervention 1: Given 400 mg PO twice a day intervention 2: Given PO to match DFMO intervention 3: Given PO at 0.5 gm/m\^2/day rounded down to the nearest 250 mg dose (BSA of \< 1.4 = 500 mg/day; BSA of 1.5 - 2.0 = 750 mg/day; BSA of 2.1 - 2.5 = 1000 mg/day; BSA of \> 2.6 = 1,250 mg/day). intervention 4: Correlative studies intervention 5: Ancillary studies

Protocol documents: