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

Primary Purpose

Barretts Esophagus With Dysplasia, Intramucosal Adenocarcinoma

Status
Active
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Study Driven Procurement of Biopsies
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Barretts Esophagus With Dysplasia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of North Carolina at Chapel Hill

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Biopsy: Barrett's Esophagus, Intramucosal adenocarcinoma

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
Correlation of Mutational Load and Number of Ablation Sessions to CEIM
ML calculation will be compared to number of sessions required to achieve CEIM.
Correlation of Mutational Load and Stricture Formation
ML calculation will be compared to stricture rates.

Full Information

First Posted
February 24, 2020
Last Updated
October 3, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Interpace Diagnostics Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT04316975
Brief Title
Utility Of Mutational Load As A Predictor For Endoscopic Treatment Response In Barrett's Esophagus
Official Title
Utility Of Mutational Load As A Predictor For Endoscopic Treatment Response In Barrett's Esophagus
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 10, 2020 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Interpace Diagnostics Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Barretts Esophagus With Dysplasia, Intramucosal Adenocarcinoma

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Subjects will undergo a standard of care (SOC) esophagogastroduodenoscopy (EGD). At this visit, research biopsies will be obtained - 4 research biopsies at the midpoint of current Barrett's Esophagus (BE) OR slides will be cut from clinical Endoscopic Mucosal Resection (EMR). Slides will be analyzed 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 (Endoscopic Eradication Therapy) EET per routine standard of care at the treating institution until Complete Eradication of Intestinal Metaplasia (CEIM) is 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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
75 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Biopsy: Barrett's Esophagus, Intramucosal adenocarcinoma
Arm Type
Other
Arm Description
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
Intervention Type
Other
Intervention Name(s)
Study Driven Procurement of Biopsies
Other Intervention Name(s)
Research Biopsies
Intervention Description
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.
Primary Outcome Measure Information:
Title
Correlation of Mean Mutational Load (ML) and Treatment Resistance
Description
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.
Time Frame
Baseline until Month 24
Secondary Outcome Measure Information:
Title
Correlation of Mutational Load and Dysplasia Category
Description
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.
Time Frame
Day 1, at enrollment
Title
Correlation of Mutational Load and Number of Ablation Sessions to CEIM
Description
ML calculation will be compared to number of sessions required to achieve CEIM.
Time Frame
From Baseline until the date of first documentation of CEIM, assessed up to 24 Months
Title
Correlation of Mutational Load and Stricture Formation
Description
ML calculation will be compared to stricture rates.
Time Frame
From Baseline until the date of first documentation of CEIM, assessed up to 24 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nicholas J Shaheen, MD
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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