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

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

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.

Inclusion Criteria

Candidates for this study must meet all of the following 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
   • INR and PTT normal

Exclusion Criteria

Candidates will be ineligible for enrollment in the study if any of the following conditions apply:

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

   • 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)

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 6 months prior to the 0 month RFA visit (other than cauterization or excision of condyloma(s))

10. Prior ablation or resection therapy consisting of ≥ 75% circumference within the ETZ of anal canal.

11. History of topical therapy (e.g. Imiquimod, 5-FU, Trichloroacetic acid) within the ETZ within 3 months prior to the 0 month RFA visit

12. Hemorrhoids > grade III

13. Fecal incontinence

14. Concurrent disease requiring systemic immunosuppression therapy

15. Concurrent malignancy requiring systemic therapy

16. Life expectancy < 2 years

17. 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