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

Barretts Esophagus With Dysplasia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04316975
• Other study ID #: 19-0679
• Status: Completed
• Phase: N/A
• Start date: April 10, 2020
• Est. completion date: December 20, 2023

Study information

• Verified date: April 2024
• Source: University of North Carolina, Chapel Hill
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 20, 2023
• Est. primary completion date: December 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Barrett Esophagus
• Barretts Esophagus With Dysplasia
• Intramucosal Adenocarcinoma

Intervention

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.

Locations

Country	Name	City	State
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Interpace Diagnostics Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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