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

Alternate Title

Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III Prevention Closed 40 to 80 NCI UCIRVINE-UCI-2002-2261 NCT00118365

Objectives

1. Compare the rate of new adenomatous polyp formation in patients with a history of adenomatous polyps of the colon treated with eflornithine and sulindac vs placebo.
2. Correlate the effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa with the rate of new adenoma formation in these patients.
3. Compare the rate of side effects in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• History of ≥ 1 surgically resected adenomatous polyp of the colon measuring ≥ 3 mm within the past 5 years



• Screening colonoscopy performed within the past 6 months
  • All polyps must have been removed during colonoscopy, pathologically examined, and archived



• No prior surgical resection removing > 40 cm of the colon



• No personal or family history of familial polyposis or hereditary non-polyposis colon cancer

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• No concurrent corticosteroids on a regular or predictable intermittent basis

Radiotherapy

• No concurrent radiotherapy

Surgery

• See Disease Characteristics

Other

• Concurrent calcium supplements (≤ 1,000 mg/day) allowed
• Concurrent aspirin for cardiovascular prophylaxis (i.e., 81 mg/day) allowed
• Concurrent lipid-lowering drugs (i.e., high-dose statins) allowed
• No other concurrent nonsteroidal anti-inflammatory drugs (NSAIDs) on a regular or predictable intermittent basis
• No concurrent anticoagulants on a regular or predictable intermittent basis
• No concurrent treatment for gastric or duodenal ulcers

Patient Characteristics:

Age

• 40 to 80

Performance status

• SWOG 0-1

Life expectancy

• Not specified

Hematopoietic

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

Hepatic

• Bilirubin ≤ 2.0 mg/dL
• AST and ALT ≤ 2 times normal

Renal

• Creatinine ≤ 1.5 mg/dL
• Urine protein ≤ 1+*
• Urine casts 0-3*
• Urine WBC and RBC count 0-5 cells*

 [Note: *By urinalysis]

Gastrointestinal

• No history of inflammatory bowel disease
• No gastric or duodenal ulcers within the past 12 months
  • Gastric or duodenal ulcers that were adequately treated > 24 months ago are allowed
• No symptomatic gastric or duodenal ulcers

Other

• Not pregnant or nursing
• Negative pregnancy test
• Must have regional geographic stability over the next 36 months
• Pure tone audiometry evaluation normal
  • Patients with ≥ 20 dB of uncorrectable hearing loss (for age) of any 2 contiguous frequencies are not allowed
• No invasive malignancy within the past 5 years except adequately treated nonmelanoma skin cancer, level I (or Breslow < 0.76 mm) cutaneous melanoma, Duke's A colon cancer, stage I cervical cancer, or stage 0 chronic lymphocytic leukemia
• No severe metabolic disorder
• No other significant acute or chronic disease that would preclude study participation
• No history of abnormal wound healing or repair
• No conditions that would confer risk of abnormal wound healing or repair
• No history of allergy to NSAIDs or eflornithine

Expected Enrollment

A total of 150 additional patients (124 randomized) will be accrued for this study within 18 months.

Outcomes

Rate of new adenomatous polyp formation
Effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa
Side effects of treatment

Outline

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

Patients receive oral double placebo once daily for 4 weeks. Patients who are more than 70% compliant by pill measurement or self reporting are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral double placebo once daily.



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

In both arms, treatment continues for 36 months in the absence of unacceptable toxicity or the development of an invasive malignancy.

Trial Contact Information

Trial Lead Organizations

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

Frank Meyskens, MD, FACP, Principal investigator		Ph: 714-456-6310 Email: flmeyske@uci.edu
Eugene Gerner, PhD, Principal investigator		Ph: 520-626-2197; 800-622-2673

Registry Information
Official Title		A Phase III Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Combination of DFMO and Sulindac to Decrease the Rate of Recurrence of Adenomatous Polyps in the Colon
Trial Start Date		2005-06-29
Registered in ClinicalTrials.gov		NCT00118365
Date Submitted to PDQ		2005-04-14
Information Last Verified		2005-12-30
NCI Grant/Contract Number		P30-CA62203, R01-CA88078