Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps - Full Text View

Sponsor:	University of California, Irvine
Collaborators:	Chao Family Comprehensive Cancer Center National Cancer Institute (NCI)
Information provided by:	University of California, Irvine
ClinicalTrials.gov Identifier:	NCT00118365

Purpose

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.

Condition	Intervention	Phase
Colorectal Cancer Precancerous/Nonmalignant Condition	Drug: eflornithine plus sulindac	Phase III

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

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colonic Polyps Colorectal Cancer

Drug Information available for: Sulindac Eflornithine

U.S. FDA Resources

Further study details as provided by University of California, Irvine:

Primary Outcome Measures:

Rate of new adenomatous polyp formation [ Time Frame: 36 months post-randomization ] [ Designated as safety issue: No ]
Effects of eflornithine and sulindac on polyamine and prostaglandin content in the flat mucosa [ Time Frame: 36 months post-randomization ] [ Designated as safety issue: No ]
Side effects of treatment [ Time Frame: 42 months post-randomization ] [ Designated as safety issue: Yes ]

Enrollment:	178
Study Start Date:	June 2005
Estimated Study Completion Date:	December 2012
Primary Completion Date:	June 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: DFMO+Sulindac	Drug: eflornithine plus sulindac Patients will be randomized to 36 months of treatment with either DFMO+sulindac or placebo.
Experimental: Placebo	Drug: eflornithine plus sulindac Patients will be randomized to 36 months of treatment with either DFMO+sulindac or placebo.

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.

Eligibility

Ages Eligible for Study:	40 Years to 80 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118365

Locations

United States, California
Veterans Affairs Medical Center - Loma Linda (Pettis)
Loma Linda, California, United States, 92357
Veterans Affairs Medical Center - Long Beach
Long Beach, California, United States, 90822
Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
Orange, California, United States, 92868
Kaiser Permanente Medical Center - Sacramento
Sacramento, California, United States, 95825
United States, Colorado
Veterans Affairs Medical Center - Denver
Denver, Colorado, United States, 80220
United States, Kansas
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
Kansas City, Kansas, United States, 66160-6616

Sponsors and Collaborators

University of California, Irvine

Chao Family Comprehensive Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:	Frank L. Meyskens, MD, FACP	Chao Family Comprehensive Cancer Center
Principal Investigator:	Eugene Gerner, PhD	University of Arizona

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

McLaren CE, Fujikawa-Brooks S, Chen WP, Gillen DL, Pelot D, Gerner EW, Meyskens FL Jr. Longitudinal assessment of air conduction audiograms in a phase III clinical trial of difluoromethylornithine and sulindac for prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila Pa). 2008 Dec;1(7):514-21.

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 the prevention of sporadic colorectal adenomas: a randomized placebo-controlled, double-blind trial. Cancer Prev Res (Phila Pa). 2008 Jun;1(1):32-8.

Zell JA, Pelot D, Chen WP, McLaren CE, Gerner EW, Meyskens FL. Risk of cardiovascular events in a randomized placebo-controlled, double-blind trial of difluoromethylornithine plus sulindac for the prevention of sporadic colorectal adenomas. Cancer Prev Res (Phila). 2009 Mar;2(3):209-12. Epub 2009 Mar 3.

Gerner EW, Meyskens FL Jr. Combination chemoprevention for colon cancer targeting polyamine synthesis and inflammation. Clin Cancer Res. 2009 Feb 1;15(3):758-61. Review.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Thompson PA, Wertheim BC, Zell JA, Chen WP, McLaren CE, LaFleur BJ, Meyskens FL, Gerner EW. Levels of rectal mucosal polyamines and prostaglandin E2 predict ability of DFMO and sulindac to prevent colorectal adenoma. Gastroenterology. 2010 Sep;139(3):797-805, 805.e1. Epub 2010 Jun 9.

Responsible Party:	Frank L. Meyskens, Jr, Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
ClinicalTrials.gov Identifier:	NCT00118365 History of Changes
Other Study ID Numbers:	CDR0000429552, 2002-2261
Study First Received:	July 8, 2005
Last Updated:	April 18, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of California, Irvine:

colon cancer
rectal cancer
precancerous/nonmalignant condition

Additional relevant MeSH terms:

Colorectal Neoplasms
Disease
Precancerous Conditions
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Pathologic Processes
Eflornithine

Sulindac
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Trypanocidal Agents
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Cyclooxygenase Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents

ClinicalTrials.gov processed this record on February 09, 2012