Eflornithine to Prevent Cancer in Patients With Barrett's Esophagus
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Esophageal Cancer
Intervention: eflornithine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: University of Michigan Cancer Center Official(s) and/or principal investigator(s):
Dean E. Brenner, MD, Study Chair, Affiliation: University of Michigan Cancer Center
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.
Clinical Details
Official title: Phase IIb Chemoprevention Trial of Difluoromethylornithine (DFMO) in Human Subjects With Intestinal-Type Barrett's Esophagus
Study design: Prevention
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Tulane University School of Medicine, New Orleans, Louisiana 70112, United States
Massachusetts General Hospital Cancer Center, Boston, Massachusetts 02114, United States
University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0752, United States
Arthur G. James Cancer Hospital - Ohio State University, Columbus, Ohio 43210, United States
Veterans Affairs Medical Center - Dallas, Dallas, Texas 75216, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: October 1995
Last updated: May 23, 2008
|
