Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Related Information
Registry Information

Alternate Title

Celecoxib With or Without Eflornithine in Preventing Colorectal Cancer in Patients With Familial Adenomatous Polyposis.

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Prevention	Closed	18 to 65	NCI	MDA-ID-00109 NCI-P02-0219, N01-CN-95040, NCT00033371

Special Category: NCI Web site featured trial

Objectives

1. Compare the relative efficacy of celecoxib with or without eflornithine, as evidenced by the percentage change from baseline in the number of polyps in focal area(s) of the colorectum, in participants with familial adenomatous polyposis of the colorectum.
2. Compare the tolerability and safety of these preventive regimens in these participants.
3. Compare the percentage change in polyp size in a focal area of the colorectum in participants after receiving these regimens.
4. Compare the change in global colorectal polyp burden in participants after receiving these regimens.
5. Compare the percentage change in the area of plaque-like duodenal polyps in participants with duodenal disease at baseline.

Entry Criteria

Disease Characteristics:

• Diagnosis of familial adenomatous polyposis (FAP) of the colorectum based on 1 of the following criteria:
  • More than 100 polyps
  • More than 10 polyps and under age 40 OR more than 25 polyps and over age 40
    • Must have 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

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

Patient Characteristics:

Age:

• See Disease Characteristics
• 18 to 65

Performance status:

• Not specified

Life expectancy:

• Not specified

Cardiovascular

• No history of cardiovascular disease
• No uncontrolled hypertension
• No family history of premature coronary disease
• No uncontrolled hypercholesteremia

Endocrine

• No history of uncontrolled diabetes

Hematopoietic:

• No significant hematologic dysfunction
• WBC at least 3,000/mm³
• Platelet count at least 100,000/mm³
• Hemoglobin at least 10.0 g/dL
• CRP less than 3.0 mg/L
• No known or prior coagulopathy

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
• 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
• No history of deep venous thrombosis, pulmonary embolism, systemic lupus erythematous, family history of protein S or C deficiencies, prior heparin-induced thrombocytopenia, Factor V Leiden deficiencies or high homocysteine levels

Expected Enrollment

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

Outcomes

Efficacy of celecoxib with or without eflornithine as measured by the percent change of polyps in a focal area of the colorectum at baseline and 6 months after completion of study treatment
Tolerability and safety of celecoxib with eflornithine as measured by adverse events and serious adverse events at baseline and 6 months after completion of study treatment

Percent change in polyp size as measured by still pictures at baseline and 6 months after completion of study treatment
Change in global colorectal polyp burden as measured by videos of colonoscopy procedures at 6 months after completion of study treatment
Percentage of change in area of plaque-like duodenal polyps at baseline and 6 months after completion of study treatment
Effect on mucosal biomarkers (Ki-67, mitotic index [# and spatial distribution of mitoses], phosphorylated histone H3, p21 WAF1/Cip1, apoptosis [by TUNEL], apoptotic index, Bax, Bcl-2) at baseline and 6 mo after completion of study tx
Effects in colonic polyp and normal tissue cyclooxygenase(COX)-1 and COX-2 protein levels, PGE2, ornithine decarboxylase and polyamines at baseline and 6 months after completion of study treatment

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Patrick Lynch, MD, JD, Protocol chair		Ph: 713-794-5073; 800-392-1611 Email: plynch@mdanderson.org

Related Information

Featured trial article

Registry Information
Official Title		A Two Arm Phase II Chemoprevention Trial In Adenomatous Polyposis Coli Patients
Trial Start Date		2001-12-13
Trial Completion Date		2009-10-31 (estimated)
Registered in ClinicalTrials.gov		NCT00033371
Date Submitted to PDQ		2002-02-07
Information Last Verified		2009-06-15
NCI Grant/Contract Number		CA16672, CN95040

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