Trial Information

Randomized, Double-Blinded Phase II Trial of Esomeprazole Versus Esomeprazole + Two Doses of Aspirin in Barrett's Esophagus Patients

PRIMARY OBJECTIVES:

I. To assess the effects of a 28 day intervention with aspirin 81 mg placebo orally (PO)
once daily (QD) + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 81
mg PO QD + aspirin 325 mg placebo PO QD + esomeprazole 40 mg PO BID versus aspirin 325 mg PO
QD + aspirin 81 mg placebo PO QD + esomeprazole 40 mg PO BID on the absolute change in
tissue prostaglandin E2 (PGE2) concentration, as determined from Barrett's esophagus mucosal
biopsy samples obtained pre- and post-intervention (i.e. two pair-wise comparisons of two
different doses of active aspirin regimens versus aspirin placebo group), Specifically, the
two active aspirin + esomeprazole arms will be independently analyzed to see if they
significantly reduce the mean tissue PGE2 concentration from Pre- to Post-intervention as
compared to the aspirin placebo + esomeprazole arm.

SECONDARY OBJECTIVES:

I. To determine if the change in the tissue PGE2 concentration decreases significantly in
the aspirin placebo + esomeprazole arm.

II. To compare the change in mean tissue PGE2 concentration between the two active
intervention arms to determine which one appears the most promising for further testing.

III. To assess the effects of the three agents (arms) with respect to proliferation (Ki-67),
apoptosis (caspase-3 expression), COX-2 expression, and p16 methylation using Pre- and
Post-Intervention biopsy samples obtained from Barrett's mucosal tissue.

IV. To evaluate all adverse events associated with each of the three intervention arms.

V. To provide exploratory summaries of PGE2 concentration values by patient subgroups of
interest.

VI. To provide descriptive summaries of the esophagogastroduodenoscopy (EGD) results, the
rate of dysplasia, adverse events, and the Run-In Agent compliance on all participants that
signed a consent form and started the Run-In phase of the trial.

VII. To establish a biospecimen repository archive for future correlative studies.

OUTLINE: This is a multicenter, randomized, double-blind, placebo-controlled study. Patients
are stratified according to gender and length of Barrett segment of circumferential
involvement (5 cm vs = 5 cm). Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive two oral placebos once daily and oral esomeprazole magnesium twice
daily.

ARM II: Patients receive oral acetylsalicylic acid (aspirin) and oral placebo once daily and
oral esomeprazole magnesium twice daily.

ARM III: Patients receive a higher-dose of oral aspirin (higher than in arm II) and a
lower-dose of oral placebo (lower than in arm II) once daily and oral esomeprazole magnesium
twice daily.

In all arms, treatment continues for 28 days in the absence of unacceptable toxicity. Tissue
samples are collected before and after treatment and examined for tissue-based biomarkers
(i.e., PGE_2, Ki-67, caspase-3 apoptosis, and cyclooxygenase-2) by immunohistochemistry,
enzyme immunoassay, Western blot, and polymerase chain reaction.

After completion of study therapy, patients are followed at 30 days.