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

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.

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