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Predicting Risk of Cancer in Barrett's Esophagus (BE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Johns Hopkins University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
MCanto, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00431756
First received: February 2, 2007
Last updated: September 11, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to determine if there are any early changes in DNA markers of blood and esophageal tissue in people with gastric reflux, Barrett's esophagus or esophageal cancer that can warn of a progression to esophageal cancer.


Condition
Barrett Esophagus
Esophageal Neoplasm
Gastroesophageal Reflux

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Methylation in Cancer Progression of Barrett's Esophagus

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • early predictors of esophageal cancer [ Time Frame: 3 ] [ Designated as safety issue: No ]
    To see if changes in certain areas of DNA can predict risk for esophageal cancer


Biospecimen Retention:   Samples With DNA

approx. 24 ml blood, 1-8 esophageal mucosal pinch specimens


Estimated Enrollment: 540
Study Start Date: January 2002
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Detailed Description:

Patients with Barrett's esophagus (BE) have an increased risk of esophageal adenocarcinoma which is 40-125 fold higher than in the general population. However, the current techniques of detecting dysplasia and observing abnormal p53 immunohistochemical staining are not accurate or reliable methods for determining which BE patients will progress to cancer. DNA hypermethylation is an epigenetic process that occurs in the promoter region of certain genes, resulting in suppression of gene expression. Inactivation of specific genes via hypermethylation has been highly associated with cancer.

The primary objective of this research is to determine whether DNA hypermethylation is a biomarker that will predict which patients with BE are likely to progress to adenocarcinoma. Patients with BE and/or esophageal adenocarcinoma who undergo endoscopy at the Johns Hopkins Hospital will comprise the cohort of subjects. Gene hypermethylation will be assessed by performing methylation-specific PCR on a panel of 8 cancer-related genes.

Specific Aim 1: To compare the prevalence of gene hypermethylation in BE patients with different grades of dysplasia and/or adenocarcinoma, using archived specimens.

Specific Aim 2: To determine whether the presence of gene hypermethylation in initial biopsies of BE patients is associated with progression to adenocarcinoma, using archived specimens. To compare gene hypermethylation with currently available markers for neoplastic progression.

Specific Aim 3: To determine whether methylated DNA from BE and/or adenocarcinoma can be detected in the peripheral blood of patients, by comparing methylation profiles of esophageal biopsy specimens with peripheral blood samples taken at the same time in prospectively enrolled patients.

If hypermethylation of one or more genes is detected at an early stage in BE patients who later progress to adenocarcinoma, hypermethylation could be used as an early predictor for adenocarcinoma even before pathologic changes are evident. Furthermore, this research will help determine the specific genetic events that occur in the neoplastic transformation from BE to adenocarcinoma.

The long-term goal of this project is to determine whether hypermethylation can identify BE patients who are at high risk for neoplastic progression, thus allowing for early intervention in the form of more frequent endoscopic surveillance, chemoprevention, ablative therapy, or surgery.

  Eligibility

Ages Eligible for Study:   18 Years to 95 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

People who have esophageal cancer, Barrett's esophagus or gastro-esophageal reflux disease

Criteria

Inclusion Criteria:

  • People who are undergoing upper endoscopy as part of their medical care with a history of esophageal cancer, Barrett's esophagus, or upper gastrointestinal symptoms.

Exclusion Criteria:

  • People who are are currently having chemotherapy, or who have completed chemotherapy within the last 4 weeks.
  • People who have ever had radiation treatments to their chest.
  • People who have ever had photodynamic therapy or other mucosal ablation in the past.
  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: NCT00431756

Contacts
Contact: Marcia Canto, M.D. 410-502-2893
Contact: Hilary Cosby, RN 410-502-2893 hcosby1@jhmi.edu

Locations
United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Marcia Canto, M.D.    410-502-2893      
Principal Investigator: Marcia I. Canto, M.D.         
Johns Hopkins at Howard County General Hospital Recruiting
Columbia, Maryland, United States, 21044
Contact: Hilary Cosby, RN    410-502-2893    hcosby1@jhmi.edu   
Principal Investigator: Marcia I Canto, MD         
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Marcia Canto, M.D. Johns Hopkins Medicine
  More Information

No publications provided

Responsible Party: MCanto, Professor of Medicine and Oncology, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT00431756     History of Changes
Other Study ID Numbers: 1K23DK068149, 1K23DK068149
Study First Received: February 2, 2007
Last Updated: September 11, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Barrett's esophagus
gastroesophageal reflux disease (GERD)
esophageal cancer
DNA methylation

Additional relevant MeSH terms:
Deglutition Disorders
Digestive System Diseases
Esophageal Diseases
Esophageal Motility Disorders
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Barrett Esophagus
Esophageal Neoplasms
Gastroesophageal Reflux
Digestive System Abnormalities
Digestive System Neoplasms
Head and Neck Neoplasms
Neoplasms
Neoplasms by Site

ClinicalTrials.gov processed this record on November 19, 2014