Phase IIb Chemoprevention Trial of Difluoromethylornithine (DFMO) in Human Subjects With Intestinal-type Barrett's Esophagus
eflornithine
Digestive System Diseases+6
+ Digestive System Neoplasms
+ Esophageal Diseases
Prevention Study
Summary
Study start date: October 1, 1995
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.152 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Prevention Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 5 locations
Tulane University School of Medicine
New Orleans, United StatesOpen Tulane University School of Medicine in Google MapsMassachusetts General Hospital Cancer Center
Boston, United StatesUniversity of Michigan Comprehensive Cancer Center
Ann Arbor, United StatesArthur G. James Cancer Hospital - Ohio State University
Columbus, United States