Eflornithine to Prevent Cancer in Patients With Barrett's Esophagus

Sponsor
University of Michigan Rogel Cancer Center (Other)
Overall Status
Completed
CT.gov ID
NCT00003076
Collaborator
National Cancer Institute (NCI) (NIH)
152
5
120
30.4
0.3

Study Details

Study Description

Brief Summary

RATIONALE: Chemoprevention therapy is the use of drugs to try and prevent the development or recurrence of cancer. It is not known whether eflornithine is effective in preventing cancer in patients with Barrett's esophagus.

PURPOSE: Randomized double-blinded phase II trial to study the effectiveness of eflornithine in preventing cancer in patients with Barrett's esophagus.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

OBJECTIVES: I. Determine whether oral eflornithine (DFMO) given in this study will cause significant reduction of the Ki67 labelling index in subjects with intestinal type Barrett's esophagus and low grade dysplastic Barrett's esophagus. II. Determine whether oral DFMO will alter the pathology and morphology of Barrett's esophagus. III. Determine whether there is a difference in cellular DNA ploidy and/or nuclear or nucleolar morphometry in patients with dysplastic Barrett's esophagus and nondysplastic intestinal type Barrett's esophagus compared to normal gastric fundic mucosa. Determine whether DFMO modulates changes in these surrogate endpoint biomarkers towards normal mucosal values. IV. Determine whether cells demonstrating nuclear p53 protein accumulation are either lost or undergo a change in cellular distribution, following treatment of patients with dysplastic Barrett's mucosa with DFMO. V. Determine whether DFMO modulates changes in growth factor or oncogene expression in dysplastic Barrett's esophagus and nondysplastic intestinal type Barrett's esophagus. VI. Determine whether pathologic or biologic surrogate modulation occurring during 6 months of DFMO treatment reverts 6 months after treatment is discontinued.

OUTLINE: This is a randomized, placebo controlled, double blind prevention study. Patients are initially stratified by dysplasia status at baseline (metaplastic vs low grade dysplastic) and treatment group (placebo vs eflornithine). Patients are randomized to receive daily doses of eflornithine (DFMO) or placebo for 26 weeks. At 0, 4, 8, 12, 16, 20, and 26 weeks there are toxicity and adherence evaluations and at weeks 26 and 52 patients have follow-up endoscopies.

PROJECTED ACCRUAL: A total of a 152 evaluable patients will be accrued in this study.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
152 participants
Primary Purpose:
Prevention
Official Title:
Phase IIb Chemoprevention Trial of Difluoromethylornithine (DFMO) in Human Subjects With Intestinal-type Barrett's Esophagus
Study Start Date :
Oct 1, 1995
Actual Primary Completion Date :
Jun 1, 2002
Actual Study Completion Date :
Oct 1, 2005

Outcome Measures

Primary Outcome Measures

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    DISEASE CHARACTERISTICS: Must have a columnar lined esophagus that meets the following criteria: Specialized intestinal metaplasia Nondysplastic or low grade dysplasia Extends a minimum of 1 cm above the gastroesophageal junction

    PATIENT CHARACTERISTICS: Age: Over 18 Performance status: Karnofsky 80-100% Life expectancy: Not specified Hematopoietic: WBC greater than 4,000/mm3 Platelet count greater than 120,000/mm3 Hemoglobin greater than 12 g/dL Prothrombin time less than 3 seconds beyond control Partial thromboplastin time less than 10 seconds beyond control Hepatic: Bilirubin less than 1.5 mg/dL Transaminases less than 1.5 times normal Renal: Creatinine less than 1.5 mg/dL Urinalysis: less than 1+ protein, 0-3 urinary casts, 0-5 white blood cells and red blood cells Cardiovascular: No severe dyspnea at rest, orthopnea, edema, history of congestive heart failure requiring continued treatment, or unstable angina Neurologic: No severe degenerative neurologic disease Pulmonary: No requirement of supplemental oxygen for exertion or rest Other: No prior malignancy within 5 years No active rheumatoid arthritis, lupus or other rheumatologic autoimmune disease (no less than 2 years of quiescence if inactive) No history of abnormal wound healing No history of esophageal varices or variceal bleeding Not pregnant or nursing Negative pregnancy test Adequate contraception required of all fertile patients

    PRIOR CONCURRENT THERAPY: No regular, scheduled use of antiinflammatory medications, steroids, or anticoagulants No nutritional supplements other than two multivitamins per day or four single nutrient vitamin supplements per day

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Tulane University School of Medicine New Orleans Louisiana United States 70112
    2 Massachusetts General Hospital Cancer Center Boston Massachusetts United States 02114
    3 University of Michigan Comprehensive Cancer Center Ann Arbor Michigan United States 48109-0752
    4 Arthur G. James Cancer Hospital - Ohio State University Columbus Ohio United States 43210
    5 Veterans Affairs Medical Center - Dallas Dallas Texas United States 75216

    Sponsors and Collaborators

    • University of Michigan Rogel Cancer Center
    • National Cancer Institute (NCI)

    Investigators

    • Study Chair: Dean E. Brenner, MD, University of Michigan Rogel Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Michigan Rogel Cancer Center
    ClinicalTrials.gov Identifier:
    NCT00003076
    Other Study ID Numbers:
    • CDR0000065763
    • P30CA046592
    • CCUM-9555
    • NCI-P97-0094
    First Posted:
    Apr 23, 2004
    Last Update Posted:
    Dec 19, 2012
    Last Verified:
    Dec 1, 2012
    Keywords provided by University of Michigan Rogel Cancer Center
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 19, 2012