Celecoxib With or Without Eflornithine in Preventing Colorectal Cancer in Patients With Familial Adenomatous Polyposis
Condition: Colorectal Cancer; Familial Adenomatous Polyposis
MeSH terms: Colorectal Neoplasms; Nasopharyngeal Neoplasms; Adenomatous Polyposis Coli
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Celecoxib; Placebo; eflornithine; Laboratory biomarker analysis; Questionnaire administration
Intervention type(s): Drug; Other; Drug; Other; Other
Intervention description(s): Given 400 mg PO twice a day; Given PO to match DFMO; 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).; Correlative studies; Ancillary studies
Other intervention name(s): Celebrex; SC-58635; PLCB; 2-difluoromethylornithine; DFMO; difluromethylornithine; Survey
Intervention MeSH terms: Eflornithine; Celecoxib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment