Barrett EsophagusPhase 2NCT02521285
Aspirin in Preventing Disease Recurrence in Patients With Barrett Esophagus After Successful Elimination by Radiofrequency Ablation
A Phase 2 study testing Aspirin, Laboratory Biomarker Analysis and Questionnaire Administration in people with Barrett Esophagus and Esophageal Adenocarcinoma, run by National Cancer Institute (NCI) at 10 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Barrett Esophagus, Esophageal Adenocarcinoma
- What is being tested?
- Aspirin, Laboratory Biomarker Analysis and Questionnaire Administration
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 10 sitesin 2 countries
- Study dates
- 15 Jan 2016to 30 Mar 2027
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
United States9 sites
UCHealth University of Colorado Hospital
Aurora, Colorado, 80045
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Northwestern University
Chicago, Illinois, 60611
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030
UT MD Anderson Cancer Center
Houston, Texas, 77030
Kansas City Veterans Affairs Medical Center
Kansas City, Missouri, 64128
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
University of Pennsylvania/Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Effect of Aspirin on Biomarkers of Barrett's Esophagus After Successful Eradication of Barrett's Esophagus With Radiofrequency Ablation
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Barrett Esophagus, Esophageal Adenocarcinoma
- Being tested
- Aspirin, Laboratory Biomarker Analysis, Placebo Administration, Questionnaire Administration
- Medical subject headings
- Barrett Esophagus, Adenocarcinoma Of Esophagus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AspirinDrug
Also called Acetylsalicylic Acid, ASA, Aspergum, Ecotrin
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Placebo AdministrationOther
Given PO
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Arm A (aspirin) | Experimental | Patients receive aspirin PO QD for 12 months. Receives: Drug: Aspirin; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration |
| Arm B (placebo) | Placebo comparator | Patients receive placebo PO QD for 12 months. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in the Change of CDX2 mRNA Levels in Esophageal Mucosa Between Participants Taking Aspirin and Placebo at 12 Months (Location A)
Measured the absolute and relative values in percentage of biomarker levels CDX2 mRNA levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location A (1 cm above GE Junction.) The difference in the change were measured by the total RNAs were isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Measured: Baseline and 12 months
Differences in the Change of CDX2 Messenger Ribonucleic Acid (mRNA) Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo (Location B)
Measured the absolute and relative values change in the biomarker levels CDX2 mRNA levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the total RNAs were isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Measured: Baseline and 12 months
Differences in the Change of CDX2 Messenger Ribonucleic Acid (mRNA) Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo ( Location C)
Measured the absolute and relative values change in the biomarker levels CDX2 mRNA levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the total RNAs were isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Measured: Baseline and 12 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 12 Months (Location A)
Measured the absolute and relative values change in the biomarker levels p-p65/total p65 in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location A, 1 cm above GE Junction. The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Measured: Baseline and 12 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 12 Months (Location B)
Measured the absolute and relative values change in the biomarker levels p-p65/total p65 in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment)The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Measured: Baseline and 12 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 12 Months (Location C)
Measured the absolute and relative values change in the biomarker levels p-p65/total p65 in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Measured: Baseline and 12 months
Secondary outcomes (22)
Number of Participants With Adverse Events (AE)
Number of Participants experiencing adverse events by maximum grade (grades 1-3). Safety assessed by comparison of adverse events using the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. AEs will be assessed according to the CTCAE grade associated with the AE term. All adverse events are listed in the Adverse Events Overview.
Measured: Up to 18 months
Differences in the Change of CDX2 mRNA Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo at 18 Months (Location A)
Measured the change in the biomarker levels CDX2 mRNA levels in esophageal mucosa at baseline and 18 months for each participant taking aspirin versus placebo at Location A, 1 cm above GE Junction. The difference in the change were measured by the total RNAs will be isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Measured: Baseline to 18 months
Differences in the Change of CDX2 mRNA Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo at 18 Months (Location B)
Measured change in the biomarker levels CDX2 mRNA levels in esophageal mucosa at baseline and 18 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the total RNAs will be isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Measured: Up to 18 months
Differences in the Change of CDX2 mRNA Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo at 18 Months (Location C)
Measured the change in the biomarker levels CDX2 mRNA levels in esophageal mucosa at baseline and 18 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the total RNAs will be isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Measured: Baseline to 18 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 18 Months (Location A)
Measured the change in the biomarker levels p-p65/total p65 in the esophageal mucosa at baseline and 18 months for each participant taking aspirin versus placebo at Location A, 1 cm above GE Junction. The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Measured: Baseline up to 18 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 18 Months (Location B)
Measured the change in the biomarker levels of p-p65/total p65 in the esophageal mucosa at baseline and 18 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Measured: Baseline up to 18 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 18 Months (Location C)
Measured the change in the biomarker levels p-p65/total p65 in esophageal mucosa at baseline and 18 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Measured: Baseline up to 18 months
Differences in the Change of txb2 at 12 Months (Location A)
Measured the absolute and relative values change in the biomarker levels txb2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location A, 1 cm above GE Junction. The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of tbx2 at 12 Months (Location B)
Measured the absolute and relative values change in the biomarker levels txb2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of tbx2 at 12 Months (Location C)
Measured the absolute and relative values change in the biomarker levels txb2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of pge1 at 12 Months ( Location A)
Measured the absolute and relative values change in the biomarker levels pge1 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at A (1 cm above GE Junction). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of pge1 at 12 Months (Location B)
Measured the absolute and relative values change in the biomarker levels pge1 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of pge1 at 12 Months (Location C)
Measured the absolute and relative values change in the biomarker levels pge1 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of pge2 at 12 Months (Location A)
Measured the absolute and relative values change in the biomarker levels pge2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at A (1 cm above GE Junction). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of pge2 at 12 Months (Location B)
Measured the absolute and relative values change in the biomarker levels pge2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change in pge2 at 12 Months (Location C)
Measured the absolute and relative values change in the biomarker levels pge2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of a13pge1 at 12 Months (Location A)
Measured the absolute and relative values change in the biomarker levels a13pge1 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location A (1 cm above GE Junction). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of a13pge1 at 12 Months ( Location B)
Measured the absolute and relative values change in the biomarker levels a13pge1 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change in a13pge1 at 12 Months (Location C)
Measured the absolute and relative values change in the biomarker levels a13pge1 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of a13pge2 at 12 Months (Location A)
Measured the absolute and relative values change in the biomarker levels a13pge2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location A (1 cm above GE Junction). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of a13pge2 at 12month (Location B)
Measured the absolute and relative values change in the biomarker levels a13pge2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Differences in the Change of a13pge2 at 12 Months (Location C)
Measured the absolute and relative values change in the biomarker levels a13pge2 levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the Liquid chromatography-mass spectrometry (LC/MS/MS) analyses.
Measured: Baseline and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Aug 2015 (estimated)
- Study start15 Jan 2016
- Primary completion18 Jun 2019
- Study completion30 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Barrett EsophagusStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert S Bresalier, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02521285
- Sponsor's protocol ID
- NCI-2015-01265
- Other IDs
- NCI-2015-01265, 2013-0819, N01-CN-2012-00034, HHSN261201200034I, 2015-0819, MDA2013-02-02, N01CN00034, P30CA016672
- Status last verified
- Sep 2026
- First submitted
- 11 Aug 2015
- Last updated
- 11 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bresalier RS. Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma. Dig Dis Sci. 2018 Aug;63(8):2155-2162. doi: 10.1007/s10620-018-5149-6.
PubMed 29948566
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Aspirin on Biomarkers of Barrett's Esophagus After Successful Eradication of Barrett's Esophagus With Radiofrequency Ablation
- ClinicalTrials.gov ID
- NCT02521285
- Acronym / sponsor ID
- NCI-2015-01265
- Conditions
- Barrett Esophagus, Esophageal Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Jan 2016 (actual)
- Primary completion
- 18 Jun 2019 (actual)
- Study completion
- 30 Mar 2027 (estimated)
- First posted
- 13 Aug 2015 (estimated)
- Results
- Posted 1 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A (aspirin) | Experimental | Drug: Aspirin, Other: Laboratory Biomarker Analysis, Other: Questionnaire AdministrationPatients receive aspirin PO QD for 12 months. |
| Arm B (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Placebo Administration, Other: Questionnaire AdministrationPatients receive placebo PO QD for 12 months. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 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
Key exclusion criteria (26 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AspirinAlso: Acetylsalicylic Acid, ASA, Aspergum, EcotrinGiven PO | Drug | Arm A (aspirin) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Arm A (aspirin), Arm B (placebo) |
| Placebo AdministrationGiven PO | Other | Arm B (placebo) |
| Questionnaire AdministrationAncillary studies | Other | Arm A (aspirin), Arm B (placebo) |
Primary outcome
Difference in the Change of CDX2 mRNA Levels in Esophageal Mucosa Between Participants Taking Aspirin and Placebo at 12 Months (Location A)
Time frame: Baseline and 12 months
Measured the absolute and relative values in percentage of biomarker levels CDX2 mRNA levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location A (1 cm above GE Junction.) The difference in the change were measured by the total RNAs were isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Differences in the Change of CDX2 Messenger Ribonucleic Acid (mRNA) Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo (Location B)
Time frame: Baseline and 12 months
Measured the absolute and relative values change in the biomarker levels CDX2 mRNA levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment). The difference in the change were measured by the total RNAs were isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Differences in the Change of CDX2 Messenger Ribonucleic Acid (mRNA) Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo ( Location C)
Time frame: Baseline and 12 months
Measured the absolute and relative values change in the biomarker levels CDX2 mRNA levels in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by the total RNAs were isolated from squamous and neosquamous mucosal biopsy specimens using Trizol and quantitated by spectrophotometry.
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 12 Months (Location A)
Time frame: Baseline and 12 months
Measured the absolute and relative values change in the biomarker levels p-p65/total p65 in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location A, 1 cm above GE Junction. The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 12 Months (Location B)
Time frame: Baseline and 12 months
Measured the absolute and relative values change in the biomarker levels p-p65/total p65 in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location B (middle of former Barrett's segment)The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 12 Months (Location C)
Time frame: Baseline and 12 months
Measured the absolute and relative values change in the biomarker levels p-p65/total p65 in the esophageal mucosa at baseline and 12 months for each participant taking aspirin versus placebo at Location C (2 cm above former Barrett's segment). The difference in the change were measured by using esophageal squamous and neosquamous mucosal biopsies taken before and after treatment with aspirin, levels of phospho-p65 and total p65 were determined by Western blot and quantitated by densitometry.
22 secondary outcomes
Number of Participants With Adverse Events (AE)
Time frame: Up to 18 months
Differences in the Change of CDX2 mRNA Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo at 18 Months (Location A)
Time frame: Baseline to 18 months
Differences in the Change of CDX2 mRNA Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo at 18 Months (Location B)
Time frame: Up to 18 months
Differences in the Change of CDX2 mRNA Levels in Esophageal Squamous Tissue Between Participants Taking Aspirin Supplementation Versus Those Taking Placebo at 18 Months (Location C)
Time frame: Baseline to 18 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 18 Months (Location A)
Time frame: Baseline up to 18 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 18 Months (Location B)
Time frame: Baseline up to 18 months
Differences in the Activation Status of NF-kB by Assessing Levels of Total and Phospho-p65 and Cytoplasmic to Nuclear Translocation of Phospho-p65 at 18 Months (Location C)
Time frame: Baseline up to 18 months
Differences in the Change of txb2 at 12 Months (Location A)
Time frame: Baseline and 12 months
Differences in the Change of tbx2 at 12 Months (Location B)
Time frame: Baseline and 12 months
Differences in the Change of tbx2 at 12 Months (Location C)
Time frame: Baseline and 12 months
Differences in the Change of pge1 at 12 Months ( Location A)
Time frame: Baseline and 12 months
Differences in the Change of pge1 at 12 Months (Location B)
Time frame: Baseline and 12 months
Differences in the Change of pge1 at 12 Months (Location C)
Time frame: Baseline and 12 months
Differences in the Change of pge2 at 12 Months (Location A)
Time frame: Baseline and 12 months
Differences in the Change of pge2 at 12 Months (Location B)
Time frame: Baseline and 12 months
Differences in the Change in pge2 at 12 Months (Location C)
Time frame: Baseline and 12 months
Differences in the Change of a13pge1 at 12 Months (Location A)
Time frame: Baseline and 12 months
Differences in the Change of a13pge1 at 12 Months ( Location B)
Time frame: Baseline and 12 months
Differences in the Change in a13pge1 at 12 Months (Location C)
Time frame: Baseline and 12 months
Differences in the Change of a13pge2 at 12 Months (Location A)
Time frame: Baseline and 12 months
Differences in the Change of a13pge2 at 12month (Location B)
Time frame: Baseline and 12 months
Differences in the Change of a13pge2 at 12 Months (Location C)
Time frame: Baseline and 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29948566Bresalier RS. Chemoprevention of Barrett's Esophagus and Esophageal Adenocarcinoma. Dig Dis Sci. 2018 Aug;63(8):2155-2162. doi: 10.1007/s10620-018-5149-6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert S Bresalier principal investigator
M.D. Anderson Cancer Center
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Aspirin, Laboratory Biomarker Analysis and Questionnaire Administration in people with Barrett Esophagus and Esophageal Adenocarcinoma, run by National Cancer Institute (NCI) at 10 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in the Change of CDX2 mRNA Levels in Esophageal Mucosa Between Participants Taking Aspirin and Placebo at 12 Months (Location A) (time frame: Baseline and 12 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02521285, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2026.