RATIONALE: The use of celecoxib with or without eflornithine may be an effective way to prevent colorectal cancer in patients who have familial adenomatous polyposis.

PURPOSE: Randomized phase II trial to compare the effectiveness of celecoxib with or without eflornithine in preventing colorectal cancer in patients who have familial adenomatous polyposis.

Condition	Treatment or Intervention	Phase
Colon Cancer Rectal Cancer	Drug: celecoxib  Drug: eflornithine  Procedure: anti-cytokine therapy  Procedure: antiangiogenesis therapy  Procedure: biological response modifier therapy  Procedure: cancer prevention intervention  Procedure: chemoprevention of cancer  Procedure: growth factor antagonist therapy	Phase II

Further Study Details: 

OBJECTIVES:

• Compare the relative efficacy of celecoxib with or without eflornithine, as evidenced by the percentage change from baseline in the number of polyps in a focal area of the colorectum, in participants with familial adenomatous polyposis of the colorectum.
• Compare the tolerability and safety of these preventive regimens in these participants.
• Compare the percentage change in polyp size in a focal area of the colorectum in participants after receiving these regimens.
• Compare the change in global colorectal polyp burden in participants after receiving these regimens.
• Compare whether these regimens prevent polyp formation over a 6-month period in a field cleared of polyps in these participants.
• Compare the percentage change in the area of plaque-like duodenal polyps in participants with duodenal disease at baseline.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 1 of 2 arms.

• Arm I: Patients receive oral celecoxib twice daily and oral placebo once daily.
• Arm II: Patients receive celecoxib as in arm I and oral eflornithine once daily. Treatment in both arms continues for 6 months in the absence of disease progression or unacceptable toxicity.

Patients are followed at 1-2 months after end of study therapy.

PROJECTED ACCRUAL: A total of 120 patients (60 per arm) will be accrued for this study within 13 months.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of familial adenomatous polyposis (FAP) of the colorectum based on the following:
• Meet 1 of the following criteria:
• More than 100 polyps
• More than 10 polyps and under age 40
• More than 25 polyps and over age 40
• Characteristic family history (autosomal dominant pattern), including 1 of the following:
• More than 100 polyps in a first-degree relative
• More than 25 polyps in 2 relatives in 2 generations, including a first-degree family member
• Genetic diagnosis in a relative
• Genetic diagnosis by in vitro synthesized protein or similar assay
• No anticipated colectomy within 8 months after randomization
• Colonic and/or rectal segment endoscopy documenting 1 of the following:
• 5 or more rectal polyps each at least 2 mm in diameter
• 5 or more colon polyps each at least 2 mm in diameter, including 1 of the following:
• 3 quantifiable colon polyps greater than 3 mm in diameter
• 2 quantifiable colon polyps greater than 5 mm in diameter
• Duodenal polyps allowed

PATIENT CHARACTERISTICS: Age:

• See Disease Characteristics
• 18 to 65

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• No significant hematologic dysfunction
• WBC at least 3,000/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL

Hepatic:

• No significant hepatic dysfunction
• Bilirubin no greater than 2 times upper limit of normal (ULN)
• SGOT and SGPT no greater than 1.5 times ULN
• Alkaline phosphatase no greater than 1.5 times ULN

Renal:

• No significant renal dysfunction
• Creatinine no greater than 1.5 times ULN

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No clinically significant hearing loss, defined as:
• Hearing loss that affects everyday life or for which a hearing aid is required
• Abnormal hearing on an air conduction pure tone audiogram (exceeding 95th percentile)
• No prior hypersensitivity to cyclooxygenase-2 inhibitors, sulfonamides, NSAIDs, or salicylates
• No discrete gastric or duodenal ulcer greater than 5 mm within the past year except Helicobacter pylori-related peptic ulcer disease treated successfully with antibiotics (as documented by an endoscopy)
• No invasive malignancy within the past 5 years except stage I or II colon cancer or resected nonmelanomatous skin cancer
• No other significant medical or psychiatric problems that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• No chronic adrenocorticosteroids

Radiotherapy:

• No prior pelvic irradiation

Surgery:

• See Disease Characteristics
• At least 1 year since prior partial or complete colectomy

Other:

• At least 3 months since prior investigational agents
• At least 3 months since prior chronic non-steroidal anti-inflammatory drugs (NSAIDs) (e.g., aspirin or celecoxib)
• No other concurrent NSAIDs (e.g., aspirin, ibuprofen, or naproxen)
• No concurrent warfarin, fluconazole, or lithium

Ohio
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195,  United States; Recruiting
Texas
      MD Anderson Cancer Center at University of Texas, Houston,  Texas,  77030,  United States; Recruiting
United Kingdom, England
      St. Mark's Hospital, Harrow,  England,  HA1 3UJ,  United Kingdom; Recruiting

Study chairs or principal investigators

Patrick M. Lynch, MD, JD,  Study Chair,  M.D. Anderson Cancer Center   

Study ID Numbers:  CDR0000069278; MDA-ID-00109; NCI-P02-0219; NCT00033371
Record last reviewed:  November 2003
Last Updated:  February 7, 2005
Record first received:  April 9, 2002
ClinicalTrials.gov Identifier:  NCT00033371
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08