Phase IIb Chemoprevention Trial of Difluoromethylornithine (DFMO) in Human Subjects With Intestinal-type Barrett's Esophagus
18 Years
N/A
Both
Esophageal Cancer
Trial Information
Phase IIb Chemoprevention Trial of Difluoromethylornithine (DFMO) in Human Subjects With Intestinal-type Barrett's Esophagus
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Prevention
Principal Investigator
Dean E. Brenner, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of Michigan Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000065763
NCT ID:
NCT00003076
Start Date:
October 1995
Completion Date:
October 2005
Related Keywords:
- Esophageal Cancer
- esophageal cancer
- Barrett Esophagus
- Esophageal Diseases
- Esophageal Neoplasms
Name | Location |
|---|---|
| University of Michigan Comprehensive Cancer Center | Ann Arbor, Michigan 48109-0752 |
| Arthur G. James Cancer Hospital - Ohio State University | Columbus, Ohio 43210 |
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| Tulane University School of Medicine | New Orleans, Louisiana 70112 |
| Veterans Affairs Medical Center - Dallas | Dallas, Texas 75216 |
