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

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
American Society for Gastrointestinal Endoscopy
Information provided by (Responsible Party):
Nicholas Shaheen, MD, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier:
NCT02075905
First received: February 27, 2014
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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.


Condition
Barrett's Esophagus
Esophageal Adenocarcinoma
Intestinal Metaplasia
Dysplasia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Stratifying Risk in Barrett's Esophagus: A Pilot Study for Biomarker-based Patient Management

Further study details as provided by University of North Carolina, Chapel Hill:

Primary Outcome Measures:
  • Risk Stratification [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.


Biospecimen Retention:   Samples Without DNA

Paraffin embedded esophageal biopsies


Estimated Enrollment: 100
Study Start Date: March 2014
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
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.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

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

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02075905

Locations
United States, North Carolina
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Netherlands
Academic Medical Center
Amsterdam, Netherlands, 1100 DD
United Kingdom
University of Cambridge
Cambridge, United Kingdom, CB2 0XZ
Sponsors and Collaborators
University of North Carolina, Chapel Hill
American Society for Gastrointestinal Endoscopy
Investigators
Principal Investigator: Nicholas J Shaheen, MD, MPH UNC-Chapel Hill
  More Information

No publications provided

Responsible Party: Nicholas Shaheen, MD, Professor of Medicine and Epidemiology; Chief, Division of Gastroenterology & Hepatology, University of North Carolina, Chapel Hill
ClinicalTrials.gov Identifier: NCT02075905     History of Changes
Other Study ID Numbers: 13-3843
Study First Received: February 27, 2014
Last Updated: June 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of North Carolina, Chapel Hill:
Barrett's Esophagus
Esophageal Adenocarcinoma

Additional relevant MeSH terms:
Adenocarcinoma
Barrett Esophagus
Metaplasia
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Abnormalities
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 22, 2014