TECR & ECM Placement for Esophageal High Grade Dysplasia

Study Overview
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Brief Summary
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This study will test the safety and effectiveness of esophageal transoral endoscopic circumferential resection (TECR) using an extracellular matrix (ECM) placement to treat Barrett's esophagus in patients with high-grade dysplasia (HGD). Endoscopic circumferential resection using ECM placement has been introduced as a less invasive, externally incision-less approach to treat patients with esophageal high grade dysplasia; a pre-cancerous condition. In this procedure, the entire length of diseased (abnormal) mucosa (esophagus lining) will be removed using an endoscope that will be inserted through the mouth. The ECM will be placed over the area that is being removed with a temporary, expandable stent to prevent narrowing of the esophagus. The stent is being used to hold the ECM in place as the body begins the healing process. This stent will be removed 14 days (±4 days) after this procedure. Follow-up esophagogastroduodenoscopies (EGD), barium swallow x-ray tests, and questionnaires will take place for 12 months following the procedure. The result of this study may help doctors determine if this procedure would be a more effective treatment option for HGD in the future.

Detailed Description
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This is a single-center, prospective, single arm study involving 10 patients with an established diagnosis of Barrett's Esophagus (BE) with High Grade Dysplasia (HGD). Potential subjects will be prescreened to assess eligibility and must meet inclusion criteria. In order to make this initial qualification, pathology results of biopsies and EMR collected during initial EGD will be made available to the Investigator prior to patient consent. Following informed consent and as part of routine care, all potential participants will undergo endoscopic ultrasound (EUS) and a PET/CT scan to confirm that there is no lymph node involvement or other metastatic lesions prior to the procedure. Clinical data will be collected at baseline to assess the subjects' medical status including: demographics, medical history, physical examination, vital signs, and blood testing. Cardiac and pulmonary clearance will be obtained if needed based on medical history and will include a chest x-ray, ECG, and pulmonary function test. In addition, the subjects will complete three questionnaires prior to the procedure: dysphagia severity questionnaire, SF-36, and GERD-HRQL. At the time of the procedure, participants will undergo TECR with ECM placement using a fully covered self-expanding metal stent to temporarily hold the ECM in place. Prior to hospital discharge, a barium swallow test (BaSW) will be performed at Day 1 following the study procedure to evaluate the passage of contrast through the GEJ. If the BaSW results in suspicious findings of esophageal perforation or mucosal necrosis, an upper endoscopy will be performed for further evaluation. The first primary safety endpoint for this study will be assessed following the procedure and BaSW and before discharge from the hospital. At this time point any adverse events will be assessed and recorded. All subjects will undergo the same follow-up procedures, including questionnaires and post-procedure EGDs performed at Week 2, Month 1, Month 3, Month 6, Month 9 and Month 12 to visually assess tissue healing, recurrent disease, and if stricture formation is present. Biopsies will be taken during follow-up EGDs so that pathology can rule out recurrence of BE and HGD. Subjects will have a barium swallow x-ray at Month 1, Month 3, Month 6, Month 9, and Month 12 to evaluate the potential presence of stricture formation. During Week 2 EGD, the stent will be removed during the upper endoscopy. If at any time point a subject has dysphagia with stricture formation (30% reduction in esophageal luminal diameter), routine dilation using a balloon catheter will be performed during the EGD. Validated questionnaires including dysphagia severity questionnaire, SF-36 and GERD-HRQL will be administered to objectively assess the severity of symptoms and quality of life based upon self-reported data. Additionally, adverse events will be assessed and recorded at all follow-up time points. After completion of the Month 12 visit, subjects will be followed on a routine care basis at the Esophageal & Lung Institute.

Official Title
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A Prospective Feasibility Study to Evaluate the Safety and Efficacy of Transoral Endoscopic Circumferential Esophageal Resection With Extracellular Matrix (ECM) Placement to Treat Barrett's Esophagus With High-grade Dysplasia (HGD)

Conditions
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Barrett Esophagus, Esophagus, High Grade Dysplasia

Intervention / Treatment
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* Device: Subjects undergoing TECR with ECM placement (ACell MatriStem, Boston Scientific WallFlex))


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be at least 18 years of age and no more than 80 years of age. Have an established diagnosis of HGD a. Specific diagnosis and grading will be determined by pathology review of biopsy tissue collected during baseline EGD as part of a patient's standard of care. Have no evidence of lymphovascular invasion. Have no lymph node or other metastatic involvement based on EUS and FDG-PET/CT. Diameter of affected tissue must warrant circumferential excision a. Subjects must have biopsy confirmed HGD in three of four esophageal quadrants at two levels spaced two centimeters apart (minimum of 6/8 biopsies indicating HGD). If two biopsies are normal (contain no HGD) they must be located on separate levels in two different quadrants. 5. Must be an appropriate or reasonable surgical candidate. 6. Have demonstrated an understanding and signed an approved informed consent form for participation in this study. Exclusion Criteria: Have lesions into or deeper than mucosal layer (superficial (T1a) Esophageal adenocarcinoma). a. Those requiring endoscopic submucosal dissection (ESD) are not eligible for this study Have presence of lymphovascular invasion. Require resection length longer than 10 cm. Have any lymph node or other metastatic involvement based on EUS and FDG-PET/CT. Have history of any kind of previous esophageal surgery (i.e. anti-reflux surgery). Are pregnant or planning to become pregnant. Have coagulation disorders. Have a known hypersensitivity to porcine-based materials. Have an uncontrolled comorbid medical condition that would adversely affect participation in the trial. Has a clinically significant psychological illness that in the physician's opinion would prohibit the subject's ability to meet the protocol requirements. Are unable or unwilling to provide informed consent and/or fulfill the protocol follow-up requirements. -

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TECR & ECM<br>Subjects undergoing TECR with ECM placement Intervention is Trans-oral Endoscopic circumferential resection (TECR) with placement of extra-cellular matrix (ECM) | Device: Subjects undergoing TECR with ECM placement (ACell MatriStem, Boston Scientific WallFlex))<br>* TECR will be performed to resect the entire length and area of BE lesion. ECM PLACEMENT: Following resection, the exposed area will be covered with a 6 ply sheet of ACell MatriStem® Surgical Matrix PSMX ECM (ACell Inc., Columbia, MA). The ECM will be placed and held in position for 14 days (±4 days) using a Boston Scientific WallFlex™ Fully Covered Esophageal Stent (Boston Scientific, Boston, MA).<br>* Other names: Boston Scientific, WallFlex™ Fully Covered Esophageal Stent;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Stricture Formation | To evaluate incidence of stricture formation requiring dilation (≥30% luminal diameter reduction with dysphagia) following TECR with ECM placement. Evidence of stricture formation will be confirmed endoscopically at 2 weeks, and endoscopically and through barium swallow at Month 1, Month 3, Month 6, Month 9, and Month 12 post procedure, and the proportion of subjects with and without stricture formation at the trial endpoints will be compared to historical data. | 12 months following procedure | 
| Efficacy: Recurrent Disease | To evaluate incidence of recurrence of BE with HGD through 12 months following TECR with ECM placement. Incidence of disease recurrence will be confirmed endoscopically with pathology confirmed biopsies at 2 weeks, Month 1, Month 3, Month 6, Month 9, and Month 12 post procedure, and the proportion of subjects with and without disease recurrence at the trial endpoints will be compared to historical data. | 12 months following procedure | 
| Safety: Acute (Serious System and Procedure Related Adverse Events) | To demonstrate the acute safety of TECR with ECM placement for treatment of BE with HGD by evaluating all serious system and procedure related adverse events occurring in the first 2 weeks post procedure. | Two weeks following procedure | 
| Safety: Long-term (Study Related Adverse Events) | To demonstrate the long-term safety of TECR with ECM placement for treatment of BE with HGD by evaluating all study related adverse events occurring more than 2 weeks post procedure through 12 months post procedure. | Two weeks through 12 months post procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stent Migration | To record the incidence of stent migration at 2 weeks post procedure. Stent migration will be determined endoscopically, and defined as any movement from initial deployment location greater than 1cm. | 2 weeks | 
| Stent Integrity (e.g. Stent Fracture) | To record incidences of poor stent integrity during removal (e.g. stent fracture). | 2 weeks | 
| Additional Interventions (Number of Subsequent Follow up Treatment Interventions) | To record the number of subsequent follow up treatment interventions (aside from study-related follow up time points) required post-procedure through 12 months. | 12 months |