Anal Intraepithelial Neoplasia (AIN), High-grade Squamous Intraepithelial Lesions (HSIL)
Conditions
Keywords
anal intraepithelial neoplasia, AIN, Radiofrequency Ablation, RFA
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.
Interventions
DEVICERadiofrequency Ablation (Barrx™)
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.
Sponsors
Medtronic - MITG
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Related Adverse Events | Within 12 months post RFA | Adverse event : Device relationship - Definite, Probable, Possible |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Subject Tolerability: Post -Ablation Anal Pain | within 4 weeks post RFA | Median post-ablation anal pain from 10 patients' survey after RFA treatment. Anal pain scale range: 0-10 (minimum pain=0, maximum pain=10) |
| Quality of Life Assessment: Subject Score for Worry About Anal Canal Condition | 0-2 weeks Prior RFA and after 9-12 months post RFA | 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Radiofrequency Ablation circumferential radiofrequency ablation (RFA) to the anal canal
Radiofrequency Ablation (Barrx™): 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. | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Radiofrequency Ablation |
|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 12.35 |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Related Adverse Events
Adverse event : Device relationship - Definite, Probable, Possible
Time frame: Within 12 months post RFA
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Radiofrequency Ablation | Related Adverse Events | Definite | 1 number of participants |
| Radiofrequency Ablation | Related Adverse Events | Probable | 1 number of participants |
Secondary
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)
Time frame: 0-2 weeks Prior RFA and after 9-12 months post RFA
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Radiofrequency Ablation | Quality of Life Assessment: Subject Score for Worry About Anal Canal Condition | 0-2 weeks Prior RFA | 4.5 units on a scale |
| Radiofrequency Ablation | Quality of Life Assessment: Subject Score for Worry About Anal Canal Condition | 9 to 12 months post RFA | 0.5 units on a scale |
Secondary
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)
Time frame: within 4 weeks post RFA
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Radiofrequency Ablation | Subject Tolerability: Post -Ablation Anal Pain | 5 units on a scale |