A Safety and Tolerability of Circumferential Anal Canal Radiofrequency Ablation For Anal Intraepithelial Neoplasia

Study Overview
=================
Brief Summary
-----------------
Assess the safety, feasibility, and patient tolerability of circumferential radiofrequency ablation (RFA) to the anal canal for patients with anal intraepithelial neoplasia (AIN). Patients will have AIN with high grade squamous intraepithelial lesions (HSIL) and the RFA will be applied using the Barrx™ Ablation System.

Official Title
-----------------
A Safety and Tolerability Trial of Circumferential Anal Canal Radiofrequency Ablation For Anal Intraepithelial Neoplasia Using the Barrx™ Ablation System

Conditions
-----------------
Anal Intraepithelial Neoplasia (AIN), High-grade Squamous Intraepithelial Lesions (HSIL)

Intervention / Treatment
-----------------
* Device: Radiofrequency Ablation (Barrx™)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Candidates for this study must meet all of the following criteria: Age 18-75 years HRA 2 to 8 weeks prior to the 0 month RFA visit yielding one or more flat, non-condylomatous biopsy-proven HSILs that are Located entirely within the eligible treatment zone AND Contiguous with the squamocolumnar junction Eligible treatment zone (ETZ) is defined as 3 cm above the dentate line to the anocutaneous line AND Full anorectal circumference If female of child-bearing age, negative pregnancy test within 8 weeks of the 0 month RFA visit and declared intent to remain on birth control throughout the trial, or declaration of infertility defined as subject report of status as post-menopausal or surgically sterile (status post hysterectomy or tubal ligation). If HIV positive HIV positive on antiretroviral therapy for at least 3 months with laboratory blood work within 12 weeks prior to the 0 month visit demonstrating viral load < 50 CD4 count ≥ 250/mm3 ANC > 750/mm3 Platelet count ≥ 75,000/mm3 Hemoglobin ≥ 9.0 g/dl INR and PTT normal Exclusion Criteria Candidates will be ineligible for enrollment in the study if any of the following conditions apply: Any biopsy-proven HSIL partially outside of the ETZ (for example, an HSIL lesion with extension to the perianal skin) Any condylomas in the eligible treatment zone > 1/2 cm diameter • Note: Condylomas in the eligible treatment zone < 1/2 cm in diameter must be excised or cauterized (not treated topically) before or during Visit 1 (0 month RFA visit) Any anal or rectal pathology requiring treatment including ulcer, fistula, fissure, or proctitis Any anal stricture or stenosis in patient history or upon examination. Symptomatic scarring in anal canal (i.e. not pliable, hyperkeratosis) History of or present anal or rectal cancer History of pelvic radiation therapy History of HPV vaccination or plans to initiate HPV vaccination during the trial History of ablation or resection therapy within the ETZ within 6 months prior to the 0 month RFA visit (other than cauterization or excision of condyloma(s)) Prior ablation or resection therapy consisting of ≥ 75% circumference within the ETZ of anal canal. History of topical therapy (e.g. Imiquimod, 5-FU, Trichloroacetic acid) within the ETZ within 3 months prior to the 0 month RFA visit Hemorrhoids > grade III Fecal incontinence Concurrent disease requiring systemic immunosuppression therapy Concurrent malignancy requiring systemic therapy Life expectancy < 2 years Subject is on a platelet inhibiting agent (i.e. Aspirin, Clopidogrel, NSAIDS) and/or anti-thrombotic agent (Heparin, Warfarin) and unable to discontinue 7 days before and after treatment for 14 days total. Exception: Aspirin 81 mg PO daily does not need to be discontinued

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>circumferential radiofrequency ablation (RFA) to the anal canal | Device: Radiofrequency Ablation (Barrx™)<br>* Anal canal RFA is performed to the full anal canal, 3 cm above the dentate line to the anocutaneous line proximal to the verge. The procedure entails Barrx60 ablation device, introducing the device into the anus through the anoscope, placing the electrode surface in contact with the target tissue and delivering 3 bursts of energy in rapid succession at an energy density setting of 12 J/cm2.<br>* Other names: Barrx™ Ablation System;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Related Adverse Events | Adverse event : Device relationship - Definite, Probable, Possible | Within 12 months post RFA | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject Tolerability: Post -Ablation Anal Pain | Median post-ablation anal pain from 10 patients' survey after RFA treatment. Anal pain scale range: 0-10 (minimum pain=0, maximum pain=10) | within 4 weeks post RFA | 
| Quality of Life Assessment: Subject Score for Worry About Anal Canal Condition | Median from subject scores for worry about anal canal condition at 0-2 weeks prior to RFA treatment and after 9-12 months post RFA. Median scale range: 0-10 (minimum concern=0, maximum concern=10) | 0-2 weeks Prior RFA and after 9-12 months post RFA | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
anal intraepithelial neoplasia, AIN, Radiofrequency Ablation, RFA