A Safety and Efficacy Trial of Circumferential Anal Canal Radiofrequency Ablation for High-Grade Anal Intraepithelial Neoplasia Using the BARRX™ Anorectal Wand

The purpose of this research is to assess the safety and effectiveness of circumferential radiofrequency ablation (RFA) to the anal canal using the BarrxTM Ablation System to destroy anal high-grade squamous intraepithelial lesions (HSIL). The BarrxTM Ablation System used in this study comprises an RFA generator (Barrx™ FLEX) and the BarrxTM Anorectal Wand. The generator and wand are cleared by the Food and Drug Administration (FDA) for human use and the wand is specifically cleared for treatment of anal intraepithelial neoplasia (AIN). AIN is a precancerous condition. HSIL is an advanced form of AIN. The presence of HSIL has traditionally warranted treatment. RFA has been shown in many studies to effectively and safely destroy precancerous cells in a condition called Barrett's esophagus, which is a precancerous condition of the esophagus (the swallowing tube). Recent studies have shown that RFA may offer the same benefits for those with HSIL in the anal canal. In particular, ablation of the entire circumference of the canal seems to reduce recurrence of HSIL in other locations of the anal canal.

This study will last between 12 to 15 months. Subjects will be required to undergo 5 to 8 study visits as outlined below that are carried out by the study doctors or the physician assistant. Most visits will last approximately one hour. Some may be shorter and some may be longer. Up to seventy (70) volunteers will participate in this study at several locations.

Study Overview

• Status: Unknown
• Conditions: Anal Cancer; Human Papillomavirus Infection; Human Papilloma Virus; HSIL, High Grade Squamous Intraepithelial Lesions; HPV-Related Squamous Cell Carcinoma; Ain III
• Intervention / Treatment: Device: BARRX™ Anorectal Wand

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Murad M Khan, BA; Phone Number: 212-242-6500; Email: murad.khan@icahn.mssm.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10011
      • Recruiting
      • Laser Surgery Care
      • Contact: Stephen E Goldstone, MD; Phone Number: 212-242-6500; Email: goldstone.stephen@gmail.com
      • Principal Investigator: Stephen E Goldstone, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18-75 years

2. 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

3. Eligible treatment zone (ETZ) is defined as

   • 3 cm above the dentate line to the anocutaneous line AND
   • Full anorectal circumference
4. 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).

5. 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

Exclusion Criteria:

1. Any biopsy-proven HSIL partially outside of the ETZ (for example, an HSIL lesion with extension to the perianal skin)
2. Any condylomas in the eligible treatment zone > 1/2 cm diameter
3. Any anal or rectal pathology requiring treatment including ulcer, fistula, fissure, or proctitis
4. Any anal stricture or stenosis in patient history or upon examination.
5. Symptomatic scarring in anal canal (i.e. not pliable, hyperkeratosis)
6. History of or present anal or rectal cancer
7. History of pelvic radiation therapy
8. History of HPV vaccination or plans to initiate HPV vaccination during the trial
9. History of ablation or resection therapy within the ETZ within 3 months prior to the 0 month RFA visit (other than cauterization or excision of condylomata)

10. History of topical therapy (e.g. Imiquimod, 5-FU, Trichloroacetic acid) within the

    ETZ within 3 months prior to the 0 month RFA visit

11. Hemorrhoids > grade III
12. Fecal incontinence
13. Concurrent disease requiring systemic immunosuppression therapy
14. Concurrent malignancy requiring systemic therapy
15. Life expectancy < 2 years

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent of patients who have histologically cleared high-grade squamous intraepithelial lesions (HSIL) at the SCJ at 12 months as measured by HRA	Histologic clearance of all HSIL within the ETZ on a patient and lesion basis at 12 months from first RFA	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Persistence of treated HSIL index lesions	3 months post RFA
Safety of circumferential ablation of anal canal HSIL using the Barrx™ Anorectal Wand as defined by number of patients with adverse events (including prolonged pain, bleeding, anal strictures, etc).	12 months
Percent of patients who have histologically cleared low-grade squamous intraepithelial lesions (LSIL) at the SCJ at 12 months as measured by HRA	12 months

Collaborators and Investigators

• Sponsor: Stephen E. Goldstone

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2017
• Primary Completion (Anticipated): October 1, 2019
• Study Completion (Anticipated): October 1, 2020

Study Registration Dates

• First Submitted: September 20, 2017
• First Submitted That Met QC Criteria: October 4, 2017
• First Posted (Actual): October 5, 2017

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: October 4, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; DNA Virus Infections; Intestinal Neoplasms; Rectal Diseases; Tumor Virus Infections; Colorectal Neoplasms; Neoplasms, Squamous Cell; Rectal Neoplasms; Anus Diseases; Anus Neoplasms; Papillomavirus Infections; Papilloma
• Other Study ID Numbers: 01-2017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes