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

Not Applicable

Completed

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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Biopsy: Barrett's Esophagus, Intramucosal adenocarcinoma	Study Driven Procurement of Biopsies	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

Primary Outcome Measures

Name	Time	Method
Correlation of Mean Mutational Load (ML) and Treatment Resistance	Baseline until Month 24	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

Name	Time	Method
Correlation of Mutational Load and Dysplasia Category	Day 1, at enrollment	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	From Baseline until the date of first documentation of CEIM, assessed up to 24 Months	ML calculation will be compared to number of sessions required to achieve CEIM.
Correlation of Mutational Load and Stricture Formation	From Baseline until the date of first documentation of CEIM, assessed up to 24 Months	ML calculation will be compared to stricture rates.

Locations (1): University of North Carolina at Chapel Hill
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Chapel Hill, North Carolina, United States