Clinical trial NCT04316975: 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
Overall status: COMPLETED
Phase: NA
Conditions: Barretts Esophagus With Dysplasia
Intramucosal Adenocarcinoma
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Interpace Diagnostics Corporation
First posted: 2020-03-20
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: BASIC_SCIENCE

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.

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

Primary outcomes:
measure: Correlation of Mean Mutational Load (ML) and Treatment Resistance
timeFrame: Baseline until Month 24
Secondary outcomes:
measure: Correlation of Mutational Load and Dysplasia Category
timeFrame: Day 1, at enrollment
measure: Correlation of Mutational Load and Number of Ablation Sessions to CEIM
timeFrame: From Baseline until the date of first documentation of CEIM, assessed up to 24 Months
measure: Correlation of Mutational Load and Stricture Formation
timeFrame: From Baseline until the date of first documentation of CEIM, assessed up to 24 Months
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Nicholas J Shaheen, MD
role: PRINCIPAL_INVESTIGATOR
References: