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

Alternate Title

Eflornithine Plus Sulindac in Preventing Colorectal Cancer in Patients Who Have Had Surgery to Remove Benign Colorectal Polyps

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Prevention Closed 40 to 80 NCI UCIRVINE-97-05 NCI-P00-0150, NCT00005882

Objectives

1. Compare the efficacy of eflornithine (DFMO) and sulindac vs placebo in modulating a panel of surrogate endpoint biomarkers (SEB) of particular relevance in colorectal neoplasia, including quantitative histopathology, uninduced apoptosis, proliferative (Ki67) and preneoplastic (CEA, sialyl-TN, p53, and bcl-2) features, and polyamine and PGE2 levels in patients with at least one previously resected colorectal adenoma.
2. Determine the relationship between the modulation of SEB in flat mucosa and the development of interval incident colorectal adenomas in these patients.

Entry Criteria

Disease Characteristics:

• At least 1 prior resected colorectal adenoma within the past 5 years
  • At least 3 mm in size



• No personal or family history of familial adenomatous polyposis

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• No concurrent chemotherapy

Endocrine therapy:

• No concurrent corticosteroids

Radiotherapy:

• No concurrent radiotherapy

Surgery:

• See Disease Characteristics

Other:

• No other concurrent nonsteroidal anti-inflammatories or anticoagulants administered on a regular or predictable intermittent basis
• No concurrent aspirin greater than 81 mg per day or 325 mg twice a week for cardiovascular disease prophylaxis
• No concurrent calcium supplements greater than 500 mg/day

Patient Characteristics:

Age:

• 40 to 80

Performance status:

• SWOG 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Hematocrit at least 35%
• WBC at least 4,000/mm³
• Platelet count at least 100,000/mm³

Hepatic:

• Bilirubin no greater than 2.0 mg/dL
• AST and ALT no greater than 2 times normal

Renal:

• Creatinine no greater than 1.5 mg/dL
• No greater than 1+ protein, 0-3 casts, and 0-5 WBCs and RBCs in urine

Gastrointestinal:

• No requirement for special diet or additives
• No diet that would preclude taking study medications
• No gastric or duodenal ulcer within the past year
• No inflammatory bowel disease

Other:

• No more than 20 dB hearing loss for age at any frequency
• No prior or concurrent invasive cancer within the past 5 years except nonmelanomatous skin cancer, melanoma in situ, stage I cervical cancer, stage I colon cancer, or stage 0 chronic lymphocytic leukemia
• No severe metabolic disorder or other acute or chronic diseases
• No history of or predisposition to abnormal wound healing or repair
• No allergies to nonsteroidal anti-inflammatories or eflornithine
• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

Approximately 240 patients (120 per treatment arm) will be accrued for this study within 18 months.

Outline

This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to aspirin use (yes vs no) and participating center.

Patients receive oral placebo daily for the first 4 weeks. Patients who are compliant and take the placebo 5 to 7 days each week are randomized to one of two treatment arms.

• Arm I: Patients receive oral sulindac and oral eflornithine (DFMO) daily.



• Arm II: Patients receive oral placebo daily.

Treatment continues for 3 years in the absence of disease progression or unacceptable toxicity.

Trial Contact Information

Trial Lead Organizations

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center

Frank Meyskens, MD, FACP, Protocol chair		Ph: 714-456-6310 Email: flmeyske@uci.edu

Registry Information
Official Title		A Phase II Clinical Trial of a Randomized, Double-Blind, Placebo Controlled Clinical Trial of DFMO and Sulindac Against Various Endpoints of Colorectal Pathobiology in a Cohort of Individuals at Increased Risk of Colorectal Carcinoma
Trial Start Date		2000-06-27
Registered in ClinicalTrials.gov		NCT00005882
Date Submitted to PDQ		2000-05-01
Information Last Verified		2003-03-26
NCI Grant/Contract Number		P30-CA62203