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

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Biomarker/Laboratory analysis, Prevention Active 18 and over NCI MAYO-MAY04-4-01 MAY04-4-01, NCT00474903

Objectives

Primary

1. Compare the effects of esomeprazole magnesium with vs without acetylsalicylic acid on the absolute change in tissue PGE₂ concentration in mucosal biopsy samples from patients with Barrett esophagus.

Secondary

1. Determine if the change in the tissue PGE₂ concentration decreases significantly in patients treated with esomeprazole magnesium.
2. Compare the change in mean tissue PGE₂ concentration in patients treated with these regimens.
3. Determine the effects of these regimens on proliferation (Ki-67), apoptosis (caspase-3 expression), cyclooxygenase-2 expression, and p16 methylation in these patients.
4. Determine the effects of these regimens on serum salicylate levels in these patients.
5. Determine adverse events in patients treated with these regimens.
6. Provide descriptive summaries of the esophagogastroduodenoscopy results, the rate of dysplasia, and adverse events.
7. Provide exploratory summaries of PGE₂ concentration values by patient subgroups of interest.

Entry 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

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

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

Expected Enrollment

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

Outcomes

Change in mean tissue PGE2 concentration from the pre-intervention to the post-intervention evaluation

Change in PGE2 concentration from the pre-intervention to the post-intervention evaluation (arm I)
Comparison of the change in PGE2 concentration (arms II and III)
Effects of treatment on proliferation (Ki-67), apoptosis (caspase-3 expression), cyclooxygenase-2 expression, p16 methylation, and salicylate levels
Adverse events

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., PGE₂, 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.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Paul Limburg, MD, MPH, Principal investigator		Ph: 507-284-2511

U.S.A.
Arizona
	Scottsdale
	Mayo Clinic Scottsdale
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
California
	San Francisco
	Kaiser Permanente Medical Center - San Francisco Geary Campus
		Douglas Corley, MD, PhD	Ph:  415-833-2000
Florida
	Jacksonville
	Mayo Clinic - Jacksonville
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Illinois
	Hines
	Veterans Affairs Medical Center - Hines
		Stephen Sontag, MD	Ph:  708-202-2182
			Email: Stephen.Sontag@med.va.gov
Massachusetts
	Boston
	Massachusetts General Hospital
		Clinical Trials Office - Massachusetts General Hospital	Ph:  877-726-5130
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623
Missouri
	Kansas City
	Veterans Affairs Medical Center - Kansas City
		Prateek Sharma, MD	Ph:  816-861-4700 ext. 56737
	Saint Louis
	Saint Louis University Cancer Center
		Clinical Trials Office - Saint Louis University Cancer Center	Ph:  314-977-4440
Pennsylvania
	Philadelphia
	Fox Chase Cancer Center - Philadelphia
		Clinical Trials Office - Fox Chase Cancer Center - Philadelphia	Ph:  215-728-4790
South Carolina
	Charleston
	Hollings Cancer Center at Medical University of South Carolina
		Clinical Trials Office - Hollings Cancer Center at Medical University of South Carolina	Ph:  843-792-9321
Canada
Ontario
	Toronto
	St. Michael's Hospital - Toronto
		Norman Marcon, MD	Ph:  416-864-3092
			Email: norman.marcon@utoronto.ca
United Kingdom
England
	Leicester
	Leicester Royal Infirmary
		Janusz Jankowski, MD	Ph:  44-116-254-1414

Registry Information
Official Title		Randomized, Double-Blinded Phase II Trial of Esomeprazole versus Esomeprazole + Two Doses of Aspirin in Barrett's Esophagus Patients
Trial Start Date		2007-04-26
Trial Completion Date		2009-04-01 (estimated)
Registered in ClinicalTrials.gov		NCT00474903
Date Submitted to PDQ		2007-04-19
Information Last Verified		2009-01-06
NCI Grant/Contract Number		CA15083, CN35000

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