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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

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

NCT ID

NCT04316975

First Posted

February 24, 2020

Last Updated

October 3, 2023

Sponsor

University of North Carolina, Chapel Hill

Collaborators

Interpace Diagnostics Corporation

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

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

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

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

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

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

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

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