Utility Of Mutational Load As A Predictor For Endoscopic Treatment Response In Barrett's Esophagus

To evaluate association between mutational load (ML) from esophageal biopsy specimens in pre-endoscopic eradication therapy (EET) in Barrett's Esophagus (BE) or Intramucosal adenocarcinoma (IMC) patients and treatment resistance (treatment resistance will be defined as disease recurrence and/or need for additional intervention such as increased acid suppression, need for anti-reflux surgery, or use of alternate ablative modality).

Study Overview

• Status: Completed
• Conditions: Barretts Esophagus With Dysplasia; Intramucosal Adenocarcinoma
• Intervention / Treatment: Other: Study Driven Procurement of Biopsies

Detailed Description

Potential subjects will be identified via protocol and Institutional Review Board (IRB) methods prior to obtaining written informed consent. Once written informed consent is obtained, subjects will continue with planned routine care upper endoscopy. During the first study visit an upper endoscopy will be performed. At this visit, research specimens will be obtained for mutational load (ML) analysis and gastroenterologist (GI) pathologist diagnosis for the presence of adenocarcinoma or degrees of dysplasia. ML will be correlated to the pathology diagnosis on this research biopsy. Subjects will then undergo EET per routine standard of care at the treating institution until CEIM achieved. Subjects will be followed (data collection only) during treatment period until CEIM is achieved. After subjects reach CEIM, four additional research biopsies will be collected, from the midpoint of previous BE site.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• No prior history of endoscopic treatment therapy for BE

• Previously untreated "treatment naïve" disease history with confirmed histopathology analysis of at least one of the following:

  • Low- or high-grade dysplastic BE (history of endoscopic mucosal resection (EMR)) is allowable or
  • Intramucosal adenocarcinoma (IMC)
• BE lesion length of at least: C0, M1
• At least 18 years of age at time of consent
• Able and willing to provide written informed consent
• Able and willing to comply with required study procedures and follow-up schedule

Exclusion Criteria:

• History of endoscopic intervention for the treatment of gastroesophageal reflux disease (GERD), BE, or IMC (prior EMR is allowable)
• Current esophageal stenosis/stricture preventing advancement of a therapeutic scope or significant esophageal anatomic abnormalities (masses, obstructive lesions, etc.)
• Dysplasia of intestinal metaplasia (IM) confined only to the gastric cardia (BE Prague Criteria: C0M0)
• Uncontrolled coagulopathy
• Severe medical comorbidities precluding endoscopy, or limiting life expectancy to less than 2 years in the judgment of the endoscopist
• Known portal hypertension, visible esophageal varices, or history of esophageal varices
• Previous esophagectomy surgery involving the gastroesophageal junction (history of a fundoplication is OK)
• General poor health, multiple co-morbidities placing the patient at risk, or otherwise unsuitable for trial participation
• Subject has any condition that, in the opinion of the investigator or sponsor, would interfere with accurate interpretation of the study endpoints or preclude participation in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Biopsy: Barrett's Esophagus, Intramucosal adenocarcinoma; Subjects will undergo standard of care (SOC) standard esophagogastroduodenoscopy (EGD) for the treatment of their condition (BE or IMC). Four (4) research biopsies will be taken from the midpoint of current disease. In cases where EMR (Endoscopic Mucosal Resection) is performed clinically, no research biopsies will be taken. Following CEIM, four (4) additional research biopsies will be collected, from the midpoint of previous BE site. Laboratory Biomarker Analysis: Correlative studies Esophagogastroduodenoscopy: Standard of care, research biopsies will be collected if clinical biopsies are taken

Other: Study Driven Procurement of Biopsies; Four research biopsies collected at the midpoint of current BE or IMC at Baseline and after reaching CEIM. Biopsies will be used to calculate ML scores both pre and post EET.; Other Names: Research Biopsies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Mean Mutational Load (ML) and Treatment Resistance	Treatment resistance will be assessed as a dichotomous variable and defined as those with one or more of the following features: disease recurrence, need for increased acid suppression, need for anti-reflux surgery, or use of alternate ablative modality. The association between pre-EET ML and treatment resistance will be calculated using the difference between the two mean ML values.	Baseline until Month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of Mutational Load and Dysplasia Category	The worst pathologic diagnosis at baseline will be recorded and ML between the three dysplasia groups (low grade dysplasia, high grade dysplasia, and esophageal adenocarcinoma) will be compared.	Day 1, at enrollment
Correlation of Mutational Load and Number of Ablation Sessions to CEIM	ML calculation will be compared to number of sessions required to achieve CEIM.	From Baseline until the date of first documentation of CEIM, assessed up to 24 Months
Correlation of Mutational Load and Stricture Formation	ML calculation will be compared to stricture rates.	From Baseline until the date of first documentation of CEIM, assessed up to 24 Months

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Interpace Diagnostics Corporation
• Investigators: Principal Investigator: Nicholas J Shaheen, MD, University of North Carolina, Chapel Hill

Study record dates

Study Major Dates

• Study Start (Actual): April 10, 2020
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): December 20, 2023

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: March 19, 2020
• First Posted (Actual): March 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: April 5, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Gastrointestinal Diseases; Esophageal Diseases; Precancerous Conditions; Barrett Esophagus
• Other Study ID Numbers: 19-0679

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No