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Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02521285
Recruitment Status : Active, not recruiting
First Posted : August 13, 2015
Last Update Posted : August 12, 2019
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This randomized phase II trial studies the safety of and how well aspirin works in preventing Barrett's esophagus from returning after it has been successfully eliminated by radiofrequency ablation. Studying samples of tissue from patients with Barrett's esophagus for the levels of a specific protein that is linked to developing Barrett's esophagus may help doctors learn whether aspirin can prevent it from returning after it has been successfully treated.

Condition or disease Intervention/treatment Phase
Barrett Esophagus Barrett Esophagus-Negative for Dysplasia Dysplasia in Barrett Esophagus Drug: Aspirin Other: Laboratory Biomarker Analysis Other: Placebo Other: Questionnaire Administration Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To conduct a randomized, double blind, placebo-controlled phase II chemoprevention trial, investigating whether supplementation with aspirin 325 mg/day for 12 months is safe and reduces the expression of CDX2 messenger ribonucleic acid (mRNA) (a biomarker which has been associated with the risk of developing Barrett's esophagus [BE]) in comparison to placebo after successful radiofrequency ablation (RFA).

SECONDARY OBJECTIVES:

I. To assess safety at 12 months. II. To assess differences in the expression of CDX2 at 18 months, activation status of NF-kB by assessing levels of total and phosphorylated (phospho)-p65 and cytoplasmic to nuclear translocation of phospho-p65 which is likely to be affected by aspirin.

III. To assess the prostanoid marker, prostaglandin E2, and prostaglandin synthases, which are known to respond to aspirin and to correlation with clinicopathological factors in the esophageal cancer.

IV. To assess differences in the expression of proinflammatory cytokines known to induce activation of NFkB, i.e., TNFalpha, IL-1beta, IL-6, IL-10, IL-17A, IL-23 will be measured.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM A: Patients receive aspirin orally (PO) once daily (QD) for 12 months.

ARM B: Patients receive placebo PO QD for 12 months.

After completion of study treatment, patients are followed up at 1, 3, 6, 9, 12, and 18 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Effect of Aspirin on Biomarkers of Barrett's Esophagus After Successful Eradication of Barrett's Esophagus With Radiofrequency Ablation
Actual Study Start Date : January 15, 2016
Estimated Primary Completion Date : August 17, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin

Arm Intervention/treatment
Experimental: Arm A (aspirin)
Patients receive aspirin PO QD for 12 months.
Drug: Aspirin
Given PO
Other Names:
  • Acetylsalicylic Acid
  • ASA
  • Aspergum
  • Ecotrin
  • Empirin
  • Entericin
  • Extren
  • Measurin

Other: Laboratory Biomarker Analysis
Correlative studies

Other: Questionnaire Administration
Ancillary studies

Placebo Comparator: Arm B (placebo)
Patients receive placebo PO QD for 12 months.
Other: Laboratory Biomarker Analysis
Correlative studies

Other: Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Differences in the change of CDX2 messenger ribonucleic acid (mRNA) levels in esophageal squamous tissue between participants taking aspirin supplementation versus those taking placebo [ Time Frame: Baseline to 12 months ]
    Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.


Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 18 months ]
    Assessed according to the Common Terminology Criteria for Adverse Events version 4.0. All adverse events will be recorded and graded during clinical visits, whether or not they are considered drug related. Each treatment arm will be monitored separately for severe toxicities (grade 3 and 4 severe adverse events). At the completion of the study, the frequency of toxicities will be compared between the placebo and aspirin groups.

  2. Change in well-being [ Time Frame: Baseline to 12 months ]
    As measured by the 36-Item Short Form Health Survey. Bivariate analyses will be performed on study entry and completion of the on-drug period. Multivariate analyses will be performed between groups after controlling for potential confounders.

  3. Differences in the change of CDX2 mRNA levels in esophageal squamous tissue between participants taking aspirin supplementation versus those taking placebo [ Time Frame: Baseline to 18 months ]
    Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.

  4. Differences in the activation status of NF-kB by assessing levels of total and phospho-p65 and cytoplasmic to nuclear translocation of phospho-p65 [ Time Frame: Baseline up to 18 months ]
    Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.

  5. Differences in the prostanoid marker, prostaglandin E2, and prostaglandin synthases [ Time Frame: Baseline up to 18 months ]
    Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.

  6. Differences in the expression of proinflammatory cytokines known to induce activation of NFkB [ Time Frame: Baseline up to 18 months ]
    Both parametric (t-test) and non-parametric (Wilcoxon) tests will be performed.


Other Outcome Measures:
  1. Incidence of Barrett's esophagus (BE) recurrence [ Time Frame: Up to 18 months ]
    At all endoscopic examinations, all raised mucosal lesions and flat lesions suspicious for neoplasia will be biopsied and excised, location and size noted, and pathology material reviewed. For each participant, the surface area of recurrent BE will be estimated along with its Prague classification, histological characteristics, and location. A blinded study pathologist will review all specimens. Each biopsy will be classified using standard criteria as normal, Barrett's metaplasia, BE with low- or high-grade dysplasia, neoplasia, indefinite for dysplasia, intramucosal or invasive carcinoma.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Known diagnosis of histologically-confirmed BE with or without dysplasia (as defined by the presence of specialized columnar epithelium anywhere in the tubular esophagus with >= 1 cm of circumferential involvement or non-circumferential involvement of specialized columnar epithelium) requiring radiofrequency ablation
  • Documentation of complete ablation of BE after radiofrequency ablation on two endoscopic examinations at least 3 months apart (including no evidence of BE on surveillance biopsies) as determined by the pathologist at each site; completion of ablation should have occurred no greater than 36 months prior to randomization
  • The effects of the candidate chemoprevention agents on the developing human fetus remain incompletely defined; for this reason, persons of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a participant become pregnant or suspect she is pregnant while participating in this trial, she should inform the research personnel and her clinical care provider immediately
  • Willingness to provide tissue samples for research purposes
  • No chronic use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) or selective cyclooxygenase-2 (COX-2) inhibitors during one month prior to randomization; chronic use is defined as any aspirin or NSAID use on >= 7 days during one month preceding the beginning of randomization
  • Hemoglobin >= 10 g/dL or hematocrit >= 30% (obtained =< 45 days prior to randomization)
  • Leukocyte count >= 3,000/microliter (obtained =< 45 days prior to randomization)
  • Platelet count >= 100,000/microliter (obtained =< 45 days prior to randomization)
  • Absolute neutrophil count >= 1,500/microliter (obtained =< 45 days prior to randomization)
  • Creatinine =< 2.5 x institutional upper limit of normal (ULN) (obtained =< 45 days prior to randomization)
  • OR glomerular filtration rate (GFR) > 30 ml/min/1.73 m^2 (obtained =< 45 days prior to randomization)
  • Total bilirubin =< 2 x institutional ULN (obtained =< 45 days prior to randomization)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x institutional ULN (obtained =< 45 days prior to randomization)
  • Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN (obtained =< 45 days prior to randomization)
  • A negative serum pregnancy test at baseline, but within 21 days of randomization, for persons of childbearing potential only
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Ability to understand and the willingness to sign a written informed consent document; a legally authorized representative (LAR) may sign informed consent for persons who do not have the capacity to legally consent to take part in the study

Exclusion Criteria:

  • Inability to abstain from, NSAID (including aspirin), and selective COX-2 inhibitor therapy at the time of randomization through the completion of the study (the study period is defined as baseline to exit endoscopy at 18 months after randomization which defines the completion of the study); participants may take Tylenol and non-NSAID pain relievers
  • Current or planned use of anticoagulant drugs such as: warfarin, heparin, low molecular weight heparin, Plavix, or Aggrenox throughout the course of the study
  • Individuals taking the drugs listed below may not be randomized unless they are willing to stop the medications (and possibly change to alternative non-excluded medications to treat the same conditions) no less than 1 month prior to starting aspirin or placebo on this study; consultation with the participant's primary care provider will be obtained prior to stopping any agent; the use of the following drugs or drug classes is prohibited during aspirin/placebo treatment:

    • NSAIDs: such as aspirin, Naprosyn, ketorolac and others NSAIDs
    • COX-2 inhibitors: such as celecoxib, rofecoxib
    • Valproic acid
    • Sulfinpyrazone
    • Probenecid
    • Corticosteroids (other than short-term use defined as less than 2 weeks or pro re nata [prn (when necessary)] use of an inhaler less than twice per month)
    • Platelet aggregation inhibitors, except in a monitored antithrombotic regimen
    • Methotrexate (MTX)
    • Vaccines containing live viruses
    • Gingko
  • Individuals with uncontrolled renal insufficiency or renal failure
  • Participants with fundoplication within the past year, bariatric surgery or any other major upper gastrointestinal (GI) surgery; fundoplication more than one year ago will not be grounds for exclusion; cholecystectomy will not be grounds for exclusion
  • History of invasive cancer diagnosis =< 12 months prior to randomization, excepting nonmelanoma skin cancer; patients with T1a adenocarcinoma of the esophagus arising in the setting of Barrett's esophagus are eligible for enrollment in the trial
  • History of cancer treatment =< 12 months prior to randomization, excepting hormonal therapy (except treatment for non-melanoma skin cancer or carcinoma-in-situ of the cervix)
  • Receipt of any other investigational agents =< 3 months prior to randomization, except innocuous agents with no known interaction with the study agents (e.g., standard dose multivitamins or topical agents for limited skin conditions), at the discretion of the protocol lead investigator at each participating site
  • History of allergic reactions attributed to aspirin or compounds of similar chemical or biologic composition to the study agent
  • History of endoscopically or radiographically diagnosed peptic ulcer disease with upper GI bleeding during the past 5 years or history of endoscopically or radiographically diagnosed peptic ulcer disease with upper GI bleeding any time while taking aspirin
  • Uncontrolled intercurrent illness including, but not limited to: 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 or more drinks per day) or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women
  • Breast feeding women
  • Surveillance biopsies demonstrating residual BE at qualifying exam
  • Presence of an esophageal stricture defined as "any recognizable change in esophageal luminal caliber that is accompanied by symptoms of dysphagia, or any asymptomatic narrowing that either will not allow any adult endoscope to pass or allows passage with resistance"
  • Patients with human immunodeficiency virus (HIV) infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02521285


Locations
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United States, California
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
United States, Colorado
University of Colorado Hospital
Aurora, Colorado, United States, 80045
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
United States, Missouri
Kansas City Veterans Affairs Medical Center
Kansas City, Missouri, United States, 64128
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
United States, Pennsylvania
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, United States, 77030
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Canada, Ontario
Saint Michael's Hospital
Toronto, Ontario, Canada, M5B 1W8
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Robert S Bresalier M.D. Anderson Cancer Center

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02521285     History of Changes
Other Study ID Numbers: NCI-2015-01265
NCI-2015-01265 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2013-0819
N01-CN-2012-00034
HHSN261201200034I
2015-0819 ( Other Identifier: M D Anderson Cancer Center )
MDA2013-02-02 ( Other Identifier: DCP )
N01CN00034 ( U.S. NIH Grant/Contract )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 13, 2015    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: June 2019
Additional relevant MeSH terms:
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Barrett Esophagus
Precancerous Conditions
Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Aspirin
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics