Stratifying Risk in Barrett's Esophagus: A Pilot Study for Biomarker-based Patient Management

December 19, 2016 updated by: Nicholas Shaheen, MD, University of North Carolina, Chapel Hill
Subjects enrolled in this study will have biopsies obtained and sent to Dr. Fitzgerald's lab for analysis of a validated biomarker panel. Subjects will be stratified to either high or low risk of progression to esophageal adenocarcinoma (EAC) based on biomarker panel results. Biomarker panel results will not be communicated to sites. Subjects with low grade dysplasia will be offered the option of treatment (radiofrequency ablation (RFA)) as part of routine care. Subjects with low grade dysplasia who do not want RFA and subjects with no dysplasia will receive surveillance endoscopy in 1 year per routine care. All subjects will be administered a questionnaire seeking information about hypothetical willingness to be randomized to treatment or surveillance.

Study Overview

Status

Completed

Conditions

Detailed Description

The Investigators have previously completed a validation study in which they have identified a panel of biomarkers that can predict progression of subjects with BE and no dysplasia or low-grade dysplasia to esophageal adenocarcinoma (EAC). The biomarker panel, performed by the Fitzgerald lab, included ploidy (by image cytometry), AOL (histochemistry (IHC)), p53 (IHC), cyclin A (IHC), and dysplasia. These markers have been validated and demonstrated to be highly predictive of both progression to EAC, as well as the presence of occult malignancy elsewhere in the specimen (field effect). The final panel of validated biomarkers will be used in this study to identify patients at high risk of developing EAC.

The study will recruit 100 patients across 4 sites (University of North Carolina, Case Western Reserve University, University of Cambridge, and Academic Medical Center in Amsterdam). The specific aims of this pilot study are to:

  1. Demonstrate that the international, multicenter team can work together,
  2. Define the logistics of assaying biomarkers in real time such that in the future interventional trial, results could influence clinical decision-making, and,
  3. Provide further data to inform a power calculation for the full trial.

Subjects enrolled in the study will complete a questionnaire gathering hypothetical willingness to be randomized to receive endoscopic treatment intervention (RFA) or surveillance endoscopy.

Biopsy samples will be obtained from all subjects and tested for all biomarkers in the panel. Results of the biomarker panel will not be communicated to sites. Subjects with low grade dysplasia will be offered the option of receiving radiofrequency ablation (RFA) as part of routine care. Subjects with low grade dysplasia who agree to RFA will receive RFA as part of routine care. Subjects with no dysplasia and subjects with low grade dysplasia who do not want to receive RFA will receive a surveillance endoscopy in 1 year as part of routine care.

The goals of this pilot study are to ascertain the proportion of subjects in the high risk arm, to demonstrate the plausibility of performing the biomarker analysis efficiently in a sizable group of patients, to demonstrate the feasibility of delivering the endoscopic intervention (RFA), to obtain 1 year pilot data regarding progression in the high risk arm for use in sample size calculations, and to document collaboration among the centers.

Study Type

Observational

Enrollment (Actual)

111

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands, 1100 DD
        • Academic Medical Center
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0XZ
        • University of Cambridge
  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina at Chapel Hill
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Subjects with Barrett's Esophagus, coming into clinics for routine care surveillance upper endoscopy procedures.

Description

Inclusion Criteria:

  • Able to read, comprehend, and complete the consent form.
  • Aged 18 to 80.
  • Diagnosed with at least 3 centimeters (>3cm) of Barrett's Esophagus (BE) AND no dysplasia or low grade dysplasia per review by pathologist.

Exclusion Criteria:

  • Pregnant women.
  • Current use of blood thinners such as coumadin, warfarin, heparin and/or low molecular weight heparin (requires discontinuation of medication 5 days prior to and 6 days after EGD).
  • Known bleeding disorder.
  • Status post partial or complete esophageal resection.
  • Current or past diagnosis of invasive esophageal cancer (previous intramucosal cancer is allowable, if removed by endoscopic mucosal resection with histologically confirmed negative lateral and deep margins).
  • Prior ablative therapy of the esophagus including prior radiofrequency ablation (RFA), photodynamic therapy (PDT), spray cryotherapy, and other ablation therapies. Prior endoscopic mucosal resection (EMR) is acceptable.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Barrett's Esophagus-Low Grade Dysplasia
Subjects enrolled who have Barrett's Esophagus with low grade dysplasia. No research intervention is administered.
Barrett's Esophagus-no dysplasia
Subjects enrolled with Barrett's Esophagus and no dysplasia. No research intervention is administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Risk Stratification
Time Frame: Baseline
This is a pilot study the main objective of which is to determine feasibility and preparation for a larger scale study. Baseline tissue samples will be used to stratify subjects as either high or low risk of progression to esophageal adenocarcinoma (EAC) based on biomarker panel results. Biomarker panel risk stratification will be compared to data collected 1 year post enrollment regarding current pathology and ablation treatments received since enrollment.
Baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

American Society for Gastrointestinal Endoscopy

Investigators

  • Principal Investigator: Nicholas J Shaheen, MD, MPH, UNC-Chapel Hill

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (Actual)

August 1, 2015

Study Completion (Actual)

August 1, 2015

Study Registration Dates

First Submitted

February 27, 2014

First Submitted That Met QC Criteria

February 27, 2014

First Posted (Estimate)

March 3, 2014

Study Record Updates

Last Update Posted (Estimate)

December 20, 2016

Last Update Submitted That Met QC Criteria

December 19, 2016

Last Verified

December 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 13-3843

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Barrett's Esophagus

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Philippines

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe