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

NCT02521285 | Active Not Recruiting Phase 2 Results DMC

• 8 other identifiers: NCI-2015-012652013-0819N01-CN-2012-00034HHSN261201200034I2015-0819MDA2013-02-02N01CN00034P30CA016672
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 10

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.

Conditions

Barrett Esophagus; Esophageal Adenocarcinoma

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  Baseline and 12 months

Secondary Outcomes (22)

• Number of Participants With Adverse Events (AE)

  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)

  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)

  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)

  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)

  Baseline up to 18 months

Other Outcomes (3)

• Differences in the Prostanoid Marker, Prostaglandin E2, and Prostaglandin Synthases

  Baseline up to 18 months

• Differences in the Expression of Proinflammatory Cytokines Known to Induce Activation of NFkB

  Baseline up to 18 months

• Incidence of Barrett's Esophagus (BE) Recurrence

  Baseline up to 18 months

Study Arms (2)

Arm A (aspirin)

EXPERIMENTAL

Patients receive aspirin PO QD for 12 months.

Drug: Aspirin; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

Arm B (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD for 12 months.

Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Questionnaire Administration

Interventions

Aspirin DRUG

Given PO

Also known as: Acetylsalicylic Acid, ASA, Aspergum, Ecotrin, Empirin, Entericin, Extren, Measurin

Arm A (aspirin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm A (aspirin); Arm B (placebo)

Placebo Administration OTHER

Given PO

Arm B (placebo)

Questionnaire Administration OTHER

Ancillary studies

Arm A (aspirin); Arm B (placebo)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (10)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Kansas City Veterans Affairs Medical Center

Kansas City, Missouri, 64128, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania/Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Saint Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

Related Publications (1)

• 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.

  PMID: 29948566 DERIVED

MeSH Terms

Conditions

Barrett Esophagus; Adenocarcinoma Of Esophagus

Interventions

Aspirin

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Robert S. Bresalier, MD- Professor, Gastroenterology Hepat & Nutr
• Organization: UT MD Anderson Cancer Center

rbresali@mdanderson.org

(713) 745-4340

Study Officials

• Robert S Bresalier

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2015
• First Posted: August 13, 2015
• Study Start: January 15, 2016
• Primary Completion: June 18, 2019
• Study Completion (Estimated): March 30, 2027
• Last Updated: April 29, 2026
• Results First Posted: May 1, 2023

Record last verified: 2026-03

Locations

CA (1); US (9)