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

Condition(s) targeted: Colorectal Cancer; Precancerous/Nonmalignant Condition

Intervention: eflornithine (Drug); sulindac (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Chao Family Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Frank L. Meyskens, MD, FACP, Principal Investigator, Affiliation: Chao Family Comprehensive Cancer Center
Eugene Gerner, PhD, Principal Investigator, Affiliation: University of Arizona

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eflornithine and sulindac may prevent colorectal cancer. It is not yet known whether eflornithine and sulindac are more effective than a placebo in preventing colorectal cancer.

PURPOSE: This randomized phase III trial is studying eflornithine and sulindac to see how well they work compared to a placebo in preventing colorectal cancer in patients with colon polyps.

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

Study design: Prevention, Randomized, Double-Blind, Placebo Control

Primary outcome:

Rate of new adenomatous polyp formation

Effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa

Side effects of treatment

Detailed description: OBJECTIVES:

- 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.

- 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.

- Compare the rate of side effects in patients treated with these regimens.

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.

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

Minimum age: 40 Years. Maximum age: 80 Years. Gender(s): Both.

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

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

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

Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center, Orange, California 92868, United States

Kaiser Permanente Medical Center - Sacramento, Sacramento, California 95825, United States

Veterans Affairs Medical Center - Loma Linda (Pettis), Loma Linda, California 92357, United States

Veterans Affairs Medical Center - Long Beach, Long Beach, California 90822, United States

Veterans Affairs Medical Center - Denver, Denver, Colorado 80220, United States

Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-6616, United States

Flinder Medical Centres, Bedford Park, South Australia 5042, Australia

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: June 2005
Last updated: May 23, 2008