Esomeprazole With or Without Aspirin in Preventing Esophageal Cancer in Patients With Barrett Esophagus - Full Text View

Sponsor:	Mayo Clinic
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00474903

Purpose

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of esomeprazole with or without aspirin may prevent esophageal cancer in patients with Barrett esophagus.

PURPOSE: This randomized phase II trial is studying esomeprazole and aspirin to see how well they work compared with esomeprazole and placebo in preventing esophageal cancer in patients with Barrett esophagus.

Condition	Intervention	Phase
Esophageal Cancer Precancerous Condition	Drug: acetylsalicylic acid Drug: esomeprazole magnesium Other: placebo	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Masking: Double-Blind Primary Purpose: Prevention
Official Title:	Randomized, Double-Blinded Phase II Trial of Esomeprazole Versus Esomeprazole + Two Doses of Aspirin in Barrett's Esophagus Patients

Resource links provided by NLM:

MedlinePlus related topics: Cancer Esophageal Cancer Esophagus Disorders

Drug Information available for: Acetylsalicylic acid Omeprazole Omeprazole magnesium Esomeprazole Sodium Esomeprazole magnesium Magnesium

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Change in mean tissue PGE2 concentration from the pre-intervention to the post-intervention evaluation [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change in PGE2 concentration from the pre-intervention to the post-intervention evaluation (arm I) [ Designated as safety issue: No ]
Comparison of the change in PGE2 concentration (arms II and III) [ Designated as safety issue: No ]
Effects of treatment on proliferation (Ki-67), apoptosis (caspase-3 expression), cyclooxygenase-2 expression, and p16 methylation [ Designated as safety issue: No ]
Adverse events [ Designated as safety issue: Yes ]

Estimated Enrollment:	168
Study Start Date:	April 2007
Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients receive two oral placebos once daily and oral esomeprazole magnesium twice daily.	Drug: esomeprazole magnesium Given orally Other: placebo Given orally
Experimental: Arm II Patients receive oral acetylsalicylic acid (aspirin) and oral placebo once daily and oral esomeprazole magnesium twice daily.	Drug: acetylsalicylic acid Given orally Drug: esomeprazole magnesium Given orally Other: placebo Given orally
Experimental: 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.	Drug: acetylsalicylic acid Given orally Drug: esomeprazole magnesium Given orally Other: placebo Given orally

Detailed Description:

OBJECTIVES:

Primary

Compare the effects of esomeprazole magnesium with vs without acetylsalicylic acid on the absolute change in tissue PGE_2 concentration in mucosal biopsy samples from patients with Barrett esophagus.

Secondary

Determine if the change in the tissue PGE_2 concentration decreases significantly in patients treated with esomeprazole magnesium.
Compare the change in mean tissue PGE_2 concentration in patients treated with these regimens.
Determine the effects of these regimens on proliferation (Ki-67), apoptosis (caspase-3 expression), cyclooxygenase-2 expression, and p16 methylation in these patients.
Determine adverse events in patients treated with these regimens.
Provide descriptive summaries of the esophagogastroduodenoscopy results, the rate of dysplasia, and adverse events.
Provide exploratory summaries of PGE_2 concentration values by patient subgroups of interest.

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.

PROJECTED ACCRUAL: A total of 168 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed Barrett esophagus, meeting all of the following criteria:
- Presence of specialized columnar epithelium anywhere in the tubular esophagus with ≥ 2 cm of circumferential involvement
- No evidence of high-grade dysplasia or cancer by esophagogastroduodenoscopy (EGD)
- No prior histologically confirmed esophageal dysplasia, including cancer
Adequate Barrett mucosa, defined as ≥ 4 of 8 research samples with ≥ 50% intestinal metaplasia in research biopsies
No ulcer, erosion, plaque, nodule, stricture, or other luminal irregularity within the Barrett's segment or erosive esophagitis (Los Angeles classification > grade A) detected at pre-intervention EGD exam

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Hemoglobin normal
Platelet count ≥ 100,000/mm³
AST ≤ 2.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 2.5 times ULN
Bilirubin ≤ 2.5 times ULN
Creatinine ≤ 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No nasal polyps associated with asthma or induced or exacerbated by aspirin
No malignancy within the past 5 years except for nonmelanoma skin cancer
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to the study agents or rescue medication
No history of endoscopically or radiographically diagnosed peptic ulcer disease (bleeding or nonbleeding)
No other uncontrolled illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Bleeding disorder
- Vitamin K deficiency
- Alcohol abuse (defined as ingestion of ≥ 3 drinks per day)
- Psychiatric illness or social situations that would limit study compliance

PRIOR CONCURRENT THERAPY:

At least 3 months since prior chronic use (defined as ≥ 7 days during the 3 months preceding the beginning of the Run-in phase) of acetylsalicylic acid (aspirin), NSAIDs, or selective cyclooxygenase (COX-2) inhibitors
At least 3 months since prior investigational agents except innocuous agents with no known interaction with the study agents (e.g., standard dose multivitamins or topical agents for limited skin conditions)
No prior fundoplication, bariatric surgery, or any other major upper gastrointestinal surgery
- Prior cholecystectomy allowed
No other concurrent NSAIDs (including aspirin) or selective COX-2 inhibitor therapy
No concurrent anticoagulant drugs including, but not limited to, any of the following:
- Warfarin
- Heparin
- Low-molecular weight heparin
- Clopidogrel bisulfate
- Extended-release dipyridamole

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00474903

Locations

United States, Arizona
Mayo Clinic Scottsdale
Scottsdale, Arizona, United States, 85259-5499
United States, California
Kaiser Permanente Medical Center - San Francisco Geary Campus
San Francisco, California, United States, 94115
United States, Florida
Mayo Clinic - Jacksonville
Jacksonville, Florida, United States, 32224
United States, Illinois
Veterans Affairs Medical Center - Hines
Hines, Illinois, United States, 60141
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905
United States, Missouri
Veterans Affairs Medical Center - Kansas City
Kansas City, Missouri, United States, 64128
United States, Pennsylvania
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
UPMC Cancer Center at UPMC Presbyterian
Pittsburgh, Pennsylvania, United States, 15213
Canada, Ontario
St. Michael's Hospital - Toronto
Toronto, Ontario, Canada, M5B 1W8
Puerto Rico
Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus
San Juan, Puerto Rico, 00936-5067

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Paul J. Limburg, MD, MPH

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Paul J. Limburg, Mayo Clinic Cancer Center
ClinicalTrials.gov Identifier:	NCT00474903 History of Changes
Other Study ID Numbers:	CDR0000544180, MAYO-MAY04-4-01
Study First Received:	May 16, 2007
Last Updated:	December 2, 2011
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

esophageal cancer
Barrett esophagus

Additional relevant MeSH terms:

Barrett Esophagus
Disease
Esophageal Diseases
Esophageal Neoplasms
Precancerous Conditions
Digestive System Abnormalities
Digestive System Diseases
Gastrointestinal Diseases
Pathologic Processes
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Aspirin

Omeprazole
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on February 09, 2012