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

This study has been completed.
Sponsor:
Collaborators:
Chao Family Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Vanessa Wong, University of California, Irvine
ClinicalTrials.gov Identifier:
NCT00005882
First received: June 2, 2000
Last updated: January 28, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Colorectal Cancer
 Drug: eflornithine plus sulindac
 Phase 2

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

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • To measure the efficacy of DFMO plus Sulindac versus placebo in modulating biomarkers of colorectal neoplasia. [ Time Frame: 36 months post-randomization ] [ Designated as safety issue: No ]

Enrollment: 324
Study Start Date: June 2000
Study Completion Date: December 2011
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 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.

  Eligibility

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

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005882

Locations
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724-5024
United States, California
Veterans Affairs Medical Center - Loma Linda (Pettis)
Loma Linda, California, United States, 92357
Chao Family Comprehensive Cancer Center
Orange, California, United States, 92868
United States, Colorado
University of Colorado Cancer Center
Denver, Colorado, United States, 80010
Sponsors and Collaborators
University of California, Irvine
Chao Family Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Study Chair: Frank L. Meyskens, MD, FACP Chao Family Comprehensive Cancer Center
  More Information

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

Publications:

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

Responsible Party: Vanessa Wong, User Account Contact, University of California, Irvine
ClinicalTrials.gov Identifier: NCT00005882     History of Changes
Other Study ID Numbers: CDR0000067922, 1997-96, NCI-P00-0150
Study First Received: June 2, 2000
Last Updated: January 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Irvine:
colon cancer
rectal cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
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
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents

ClinicalTrials.gov processed this record on May 16, 2013