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

• BARRX™ Anorectal Wand (Device): The radiofrequency ablation (RFA) or Barrx™ Ablation System used in this protocol comprises an RFA generator (Barrx™ FLEX) and the Barrx™ Anorectal Wand. The generator and wand are cleared by the FDA for human use and the wand is specifically cleared for treatment of anal neoplasia. The present FDA indication for use statement is: "The Barrx™ catheters are indicated for use in the coagulation of bleeding and non-bleeding sites in the gastrointestinal tract including, but not limited to, the esophagus. Indications include esophageal ulcers, Mallory-Weiss tears, arteriovenous malformations, angiomata, Barrett's esophagus, Dieulafoy lesions, angiodysplasia, gastric antral vascular ectasia, and radiation proctitis."

Primary outcomes

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

Secondary outcomes

• 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]

Sex: All, ages: 18 Years to 75 Years, accepts healthy volunteers

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 Protocol and Statistical Analysis Plan (PDF, 2017-08-31)