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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00118365
First received: July 8, 2005
Last updated: March 12, 2013
Last verified: March 2013
History of Changes
  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. 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


Condition Intervention Phase
Precancerous Condition
 Other: placebo
Drug: eflornithine
Drug: sulindac
Other: laboratory biomarker analysis
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Rate of new adenomatous polyp formation [ Time Frame: Up to 36 months ] [ Designated as safety issue: No ]
    Fisher's exact test will be used to compare treatment groups with regard to the proportions of patients with at least one new adenoma. Ninety-five percent confidence intervals for the proportion of recurrent adenomas will be computed for each treatment group. For multivariate analyses, logistic regression will be used to model the presence of at least one adenoma.

  • Changes in measurements of colorectal tissue polyamine and prostaglandin E2 measurements [ Time Frame: Baseline and 36 months ] [ Designated as safety issue: No ]
    The average proportionate change from baseline in each treatment group, logarithmically transformed to reduce skewness, will be compared using the paired t-test (time 0 to time 36). Logistic regression will be used to model the proportion of interval incident adenomas.

  • Rate of side effects experienced by patients [ Time Frame: Up to 36 months ] [ Designated as safety issue: Yes ]
    Mutually exclusive categories, "no side effects" versus "side effects of grade 1 or higher" will be compared with regard to treatment groups using Fisher's exact test.


Enrollment: 150
Study Start Date: July 1998
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Arm I (placebo)
Patients receive oral double placebo once daily.
 Other: placebo
Given orally
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies
Experimental: Arm II (eflornithine and sulindac)
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.
 Drug: eflornithine
Given orally
Other Names:
  • 2-difluoromethylornithine
  • DFMO
  • difluromethylornithine
Drug: sulindac
Given orally
Other Names:
  • Aflodac
  • Algocetil
  • Clinoril
  • SULIN
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

II. 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.

III. 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.

  Eligibility

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

Criteria:

  • 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
  • SWOG 0-1
  • Bilirubin =< 2.0 mg/dL
  • AST and ALT =< 2 times normal
  • Creatinine =< 1.5 mg/dL
  • Urine protein =<, urine casts 0-3, urine WBC and RBC count 0-5 cells by urinalysis
  • 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
  • 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
  • No concurrent chemotherapy
  • No concurrent corticosteroids on a regular or predictable intermittent basis
  • No concurrent radiotherapy
  • Concurrent calcium supplements (=< 1,000 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
  • Concurrent aspirin for cardiovascular prophylaxis (i.e., 81 mg/day) allowed
  • 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
University of California Medical Center At Irvine-Orange Campus
Orange, California, United States, 92868
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Frank Meyskens University of California Medical Center At Irvine-Orange Campus
  More Information

No publications provided by National Cancer Institute (NCI)

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

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00118365     History of Changes
Other Study ID Numbers: NCI-2009-00880, UCI 97-05, R01CA088078
Study First Received: July 8, 2005
Last Updated: March 12, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Precancerous Conditions
Neoplasms
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
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on June 18, 2013