Eflornithine Plus Sulindac in Preventing Colorectal Cancer in Patients With Benign Colorectal Polyps

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005882
• Other study ID #: CDR0000067922
• Secondary ID: 1997-96NCI-P00-0
• Status: Completed
• Phase: Phase 2
• First received: June 2, 2000
• Last updated: January 28, 2013
• Start date: June 2000
• Est. completion date: December 2011

Study information

• Verified date: January 2013
• Source: University of California, Irvine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of eflornithine and sulindac may be an effective way to prevent the development of colorectal cancer in patients who have had surgery to remove benign colorectal polyps.

PURPOSE: Randomized, double-blinded, phase II trial to determine the effectiveness of eflornithine plus sulindac compared to a placebo in preventing colorectal cancer in patients who have had surgery to remove benign colorectal polyps.

Description:

OBJECTIVES:

• 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.

• Determine the relationship between the modulation of SEB in flat mucosa and the development of interval incident colorectal adenomas in these patients.

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 324
• Est. completion date: December 2011
• Est. primary completion date: June 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 80 Years

Eligibility

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

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/mm^3

• Platelet count at least 100,000/mm^3

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

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• eflornithine plus sulindac
Patients will be randomized to 36 months of treatment with either DFMO+sulindac or placebo.

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center	Denver	Colorado
United States	Veterans Affairs Medical Center - Loma Linda (Pettis)	Loma Linda	California
United States	Chao Family Comprehensive Cancer Center	Orange	California
United States	Arizona Cancer Center	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
University of California, Irvine	Chao Family Comprehensive Cancer Center, National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Abstract A29: Rectal mucosal polyamine and PGE2 levels and risk of colorectal adenomas in a phase IIb/III trial of combination difluoromethylornithine (DFMO) plus sulindac Patricia A. Thompson, Betsy C. Wertheim, Jason A. Zell, Bonnie LeFleur, Wen-Pin Che

Meyskens FL Jr, McLaren CE, Pelot D, Fujikawa-Brooks S, Carpenter PM, Hawk E, Kelloff G, Lawson MJ, Kidao J, McCracken J, Albers CG, Ahnen DJ, Turgeon DK, Goldschmid S, Lance P, Hagedorn CH, Gillen DL, Gerner EW. Difluoromethylornithine plus sulindac for — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To measure the efficacy of DFMO plus Sulindac versus placebo in modulating biomarkers of colorectal neoplasia.		36 months post-randomization	No