RFA for Flat Type High-grade and Medium-grade Intraepithelial Squamous Neoplasia

Study Overview
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Brief Summary
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Multicenter, prospective cohort clinical trial in greater China

Official Title
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A Multicenter Trial of Endoscopic Radiofrequency Ablation for High-grade and Low-grade Intraepithelial Squamous Neoplasia Using the Barrx™ Flex Radiofrequency Ablation System

Conditions
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Esophageal Squamous Cell Neoplasia (ESCN)

Intervention / Treatment
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* Device: Radiofrequency ablation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is 18-85 years of age Patient has evidence of ESCN, within the last 3 months, patient demonstrated a new diagnosis or a reconfirmed diagnosis of squamous MGIN and/or HGIN of the esophagus On endoscopic examination, subject has at least one USL that measures at least 3 cm in at least one dimension and greater than ¼ of the esophageal circumference and has MGIN or HGIN on biopsy, confirmed by central pathologist All lesions in the esophagus are completely flat (Paris type 0-IIb), both on WLE and Lugol's chromoendoscopy The maximum allowable linear length of USL-bearing esophagus is 12 cm Baseline endoscopic ultrasound (EUS) (if applicable) shows no exclusionary findings for the trial Computed Tomography )CT( scan of chest and upper third of the abdomen (if applicable) shows no exclusionary findings for the trial Based on the judgment of the study endoscopist, the patient is eligible for treatment, follow-up endoscopy, and biopsy as required by the protocol EMR or ESD occurred > 3 months before enrollment, patients may be eligible for the study if procedure was curative (negative margins and no risk of lymph node involvement) and the patient has no other findings concerning for cancer The subject is willing to provide written, informed consent to participate in this clinical study and understands the responsibilities of trial participation Exclusion Criteria: Patient has esophageal squamous cell carcinoma (ESCC) Any non-flat (Paris type 0-I, 0-IIa, 0-IIc, 0-III) abnormalities anywhere in the esophagus Any abnormalities under WLE, Lugol's chromoendoscopy or NBI that are suspicious for ESCC anywhere in the esophagus (e.g. 'pink sign' USL, defined as a color change after Lugol's staining: initially whitish yellow and pink 2-3 minutes later) Any USL with MGIN or worse on biopsy outside the treatment area Esophageal stricture preventing passage of a therapeutic endoscope Prior endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) which occurred < 3 months before enrollment Any esophageal dilation in the past 12 months Any history of a non-squamous cell cancer of the esophagus, or any history of a squamous cell cancer of the esophagus (any stage) Any previous ablative therapy within the esophagus (photodynamic therapy, multipolar electrical coagulation, argon plasma coagulation, laser treatment, or other) or any radiation therapy to the esophagus Previous esophageal surgery, except fundoplication without complications (i.e., no slippage, dysphagia, etc.) Evidence of esophageal varices detected within last 6 months or at initial RFA procedure Patient has active reflux esophagitis grade C or D Evidence of eosinophilic esophagitis on endoscopy and/or histology Inner diameter of the esophagus measuring <18 mm Report of uncontrolled coagulopathy with international normalized ratio (INR) > 2 or platelet count <75,000 platelets per µL (note: a complete blood count is not required for all subjects in this study) Patient is using anti-thrombotic agents that cannot be discontinued 7 days before and after therapeutic sessions Patient has an implantable pacing device (examples: automated implantable cardioverter defibrillator, neurostimulator, cardiac pacemaker) and has not received clearance for enrollment in this study by specialist responsible for the pacing device Patient has life expectancy less than 5 years Patient suffers from psychiatric or other illness and/or has a known history of unresolved drug or alcohol dependency that would limit ability to comprehend or follow instructions related to informed consent, post- treatment instructions, or follow-up guidelines Patient is considered to be part of a vulnerable population (e.g. prisoners or those without sufficient mental capacity) The subject has participated in an investigational drug or device research study within 30 days of enrollment that would interfere with this study Patient is pregnant or has plans to become pregnant in the ensuing 12 months (confirmation of non-pregnant status in women of child-bearing age and ability required with urine or blood test to be eligible)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Radiofrequency ablation<br>Step-wise endoscopic RFA with the Barrx™ Flex Radiofrequency Ablation System using will be performed in 3 month intervals up to 12 months. | Device: Radiofrequency ablation<br>* RFA<br>* Other names: The Barrx™ Flex Radiofrequency Ablation System;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Complete Response (CR) | The primary endpoint is the percentage of subjects with complete response (CR), defined as complete eradication of squamous histological abnormalities (MGIN or worse) within the treatment area (TA) at 12 months after the initial treatment session | 12 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response at Three Months | Number of patients with a CR after primary RFA, defined as absence of MGIN or worse in any of the biopsies from the treatment area at the three months visit | 3 Months | 
| Complete Response Within the Treatment Area | Number of patients demonstrating complete response within the treatment area (TA), defined as detection of ESCC in biopsy or resection specimen at any time within the first 12 months. | 3, 6 and 12 Month | 
| Disease Progression Outside the Treatment Area | Proportion of patients demonstrating MGIN or worse outside the TA during treatment phase or follow-up | Initial, 3, 6, 9 and 12 month |