Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Eflornithine to Prevent Cancer in Patients With Barrett's Esophagus

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Prevention	Completed	Over 18	NCI	CCUM-9555 NCI-P97-0094, NCT00003076

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.

Entry 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

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

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

Expected Enrollment

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

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. 

Trial Contact Information

Trial Lead Organizations

University of Michigan Comprehensive Cancer Center

Dean Brenner, MD, Protocol chair		Ph: 734-647-1417; 800-865-1125

Registry Information
Official Title		Phase IIb Chemoprevention Trial of Difluoromethylornithine (DFMO) in Human Subjects with Intestinal-type Barrett's Esophagus
Trial Start Date		1995-10-01
Registered in ClinicalTrials.gov		NCT00003076
Date Submitted to PDQ		1997-09-09
Information Last Verified		2006-11-06
NCI Grant/Contract Number		CA46592

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