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Barrett Esophagus

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Esophageal Diseases

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Esomeprazole

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Esomeprazole Magnesium

Paula Fernstrom

This study looks the intragastric and intraesophageal pH in patients with documented Barrett's esophagus whilst taking esomeprazole 40mg twice daily, esomeprazole 40mg three times daily, esomeprazole 20 mg three times daily.

Barrett's Esophagus - 315 - 3 Way Cross-Over

A Multicenter, Double-blind, Three-way Crossover Intraesophageal and Intragastric pH Study of Three Esomeprazole Treatment Regimens in Documented Barrett's Esophagus Patients

AstraZeneca

Tore Lind, MD - Nexium Medical Science Director

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Head and Neck Neoplasms

Esophageal Cancer

Antipyretics

Anti-Inflammatory Agents

Antirheumatic Agents

Fibrinolytic Agents

Analgesics

Platelet Aggregation Inhibitors

Aspirin

Anti-Inflammatory Agents, Non-Steroidal

Analgesics, Non-Narcotic

Cyclooxygenase Inhibitors

Patients receive two oral placebos once daily and oral esomeprazole magnesium (40 mg, twice daily).

Patients receive both an oral placebo and acetylsalicylic acid (81 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).

Patients receive both an oral placebo and acetylsalicylic acid (325 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).

acetylsalicylic acid

esomeprazole magnesium

placebo

Paul Limburg

This randomized phase II trial is studying the effect of esomeprazole magnesium and aspirin on tissue PGE2 levels compared with esomeprazole and placebo. This type of chemoprevention treatment investigates the use of certain drugs to assess whether they assist in the prevention of cancer. The use of esomeprazole magnesium with or without aspirin may help prevent esophageal cancer in patients with Barrett esophagus.

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 dysplasia status, 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 7 - 30 days.

Esomeprazole Magnesium With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus

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

The mean tissue PGE2 is reported for each Arm.

Toxicity is defined as adverse events that are classified as either possibly, probably, or definitely related to the interventional agent, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The number of patients reporting adverse events will be tabulated by grade.

National Cancer Institute (NCI)

Patients receive two oral placebos once daily and oral esomeprazole magnesium (40 mg, twice daily).

esomeprazole magnesium: Given orally placebo: Given orally

Arm I (Placebo, Esomeprazole Magnesium)

Patients receive both an oral placebo and acetylsalicylic acid (81 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).

acetylsalicylic acid: Given orally esomeprazole magnesium: Given orally placebo: Given orally

Arm II (Low-dose Aspirin, Placebo, Esomeprazole Magnesium)

Patients receive both an oral placebo and acetylsalicylic acid (325 mg dose), once daily and oral esomeprazole magnesium (40 mg, twice daily).

acetylsalicylic acid: Given orally esomeprazole magnesium: Given orally placebo: Given orally

Arm III (Higher-dose Aspirin, Palcebo, Esomeprazole Magnesium)

Total

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Two patients from ARM II withdrew due to an inadequate number of biopsies and were not included in baseline measures.

Paul J. Limburg, M.D., M.P.H.

Change in Mean Tissue Prostaglandin E2 (PGE2) Concentration as Determined From Barrett's Research Mucosal Biopsy Samples

Grade 3 or Higher

Grade 4 or Higher

All 120 patients that took study medication were evaluable for this secondary endpoint.

Toxicity

Overall Study

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Barrett's Esophagus - 315 - 3 Way Cross-Over	NCT00637559	Barrett's Esoph...	Esomeprazole Ma...	18 Years -	AstraZeneca
Esomeprazole Magnesium With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus	NCT00474903	Barrett Esophag... Esophageal Canc...	acetylsalicylic... esomeprazole ma... placebo	18 Years -	National Cancer Institute (NCI)
Esomeprazole Magnesium With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus	NCT00474903	Barrett Esophag... Esophageal Canc...	acetylsalicylic... esomeprazole ma... placebo	18 Years -	National Cancer Institute (NCI)

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