HIV-negative Subjects With Intra-anal Intraepithelial Neoplasia Containing High-Grade Squamous Intraepithelial Lesions
Conditions
Brief summary
This is a Single-center prospective pilot trial involving up to 22 subjects. This study will assess the feasibility, safety, and efficacy of radiofrequency ablation (RFA) to the anal canal using the FDA cleared HALO Ablation System to eradicate anal HSIL lesions in HIV-negative subjects with intra-anal intraepithelial neoplasia (AIN). The study intervention will demonstrate that a reasonable proportion of subjects will be histologically cleared of their anal HSIL within the ETZ in a tolerable and relatively safe manner
Interventions
DEVICERadiofrequency Ablation (RFA) using the HALO Ablation System
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
* Age 18-75 years * HRA 2 to 12 weeks prior to the 0 month RFA visit yielding one or more flat, non-condylomatous biopsy-proven HSILs that are 1. Located entirely within in the eligible treatment zone 2. Contiguous with the squamocolumnar junction Eligible treatment zone (ETZ) is defined as <!-- --> 1. 3 cm above the dentate line to the anocutaneous line 2. Half of the anorectal circumference (meaning no more than two contiguous quadrants) * 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). * HIV negative, ELISA/Western blot test obtained within 12 weeks of the 0 month RFA visit
Exclusion criteria
1. Any biopsy-proven HSIL entirely outside of the ETZ 2. Any biopsy-proven HSIL partially within the ETZ (for example, an HSIL lesion with extension to the perianal skin) 3. 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 or with IRC) before or during Visit 1 (0 month RFA visit) 4. Any anal or rectal pathology requiring treatment including ulcer, fistula, fissure, stenosis or proctitis 5. History of or present anal or rectal cancer 6. History of pelvic radiation therapy 7. History of HPV vaccination or plans to initiate HPV vaccination during the trial 8. History of ablation or resection therapy within the ETZ other than cauterization or excision of condyloma(s) 9. History of topical therapy (Imiquimod, 5-FU) within 6 months prior to the 0 month RFA visit within the ETZ 10. Hemorrhoids \> grade II 11. Fecal incontinence (that the investigator feels may impair healing) 12. Concurrent disease requiring systemic immunosuppression therapy 13. Concurrent malignancy requiring systemic therapy 14. Life expectancy \< 2 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clearance of Anal HSIL (High Grade Squamous Intraepithelial Lesion (HSIL) | 12 months | Participants with histologic clearance of anal HSIL within the ETZ (eligible treatment zone) at 12 months from first RFA treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility and Ease of Technique | 12 months | Technical feasibility of applying RFA to the anal canal. Physician's assessment of ablation as optimal (complete ablation) versus sub-optimal (incomplete ablation)in the affected area in the anal canal. Data not collected and could not be analyzed |
| Tolerability | 12 months | Subject tolerability of the RFA procedure as measured by severity. Mild: Awareness of signs and symptoms, but easily tolerated; are of a minor irritant type; causing no loss of time from normal activities; symptoms would not require medication or a medical intervention; asymptomatic lab findings; marginal clinical relevance; signs and symptoms are transient. Moderate: Discomfort severe enough to cause interference with usual activities; minimal intervention. Severe: Incapacitating with inability to do work or usual activities; signs and symptoms may be of systemic nature or require medical evaluation or treatment. |
| Adverse Events | 12 months | Any related adverse event occuring in patients enrolled in this study. Event type and relationship to the device or procedure will be measured. |
| Progression of HSIL to Cancer | 12 months | Histologic progression of HSIL to cancer as measured in biopsies read at the central pathology lab. Data not collected and could not be analyzed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| RFA Treatment Assess the feasibility, safety, and efficacy of RF to the anal canal using the HALO Ablation System to eradicate anal HSIL lesions
Radiofrequency Ablation (RFA) using the HALO Ablation System | 21 |
| Total | 21 |
Baseline characteristics
| Characteristic | RFA Treatment |
|---|---|
| Age, Continuous | 45 years |
| Gender Female | 3 Participants |
| Gender Male | 18 Participants |
| Region of Enrollment United States | 21 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 21 |
| serious Total, serious adverse events | 0 / 21 |
Outcome results
Primary
Clearance of Anal HSIL (High Grade Squamous Intraepithelial Lesion (HSIL)
Participants with histologic clearance of anal HSIL within the ETZ (eligible treatment zone) at 12 months from first RFA treatment
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RFA Treatment | Clearance of Anal HSIL (High Grade Squamous Intraepithelial Lesion (HSIL) | 19 participants w histological clearance |
Secondary
Adverse Events
Any related adverse event occuring in patients enrolled in this study. Event type and relationship to the device or procedure will be measured.
Time frame: 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| RFA Treatment | Adverse Events | 2 participants |
Secondary
Feasibility and Ease of Technique
Technical feasibility of applying RFA to the anal canal. Physician's assessment of ablation as optimal (complete ablation) versus sub-optimal (incomplete ablation)in the affected area in the anal canal. Data not collected and could not be analyzed
Time frame: 12 months
Secondary
Progression of HSIL to Cancer
Histologic progression of HSIL to cancer as measured in biopsies read at the central pathology lab. Data not collected and could not be analyzed.
Time frame: 12 months
Secondary
Tolerability
Subject tolerability of the RFA procedure as measured by severity. Mild: Awareness of signs and symptoms, but easily tolerated; are of a minor irritant type; causing no loss of time from normal activities; symptoms would not require medication or a medical intervention; asymptomatic lab findings; marginal clinical relevance; signs and symptoms are transient. Moderate: Discomfort severe enough to cause interference with usual activities; minimal intervention. Severe: Incapacitating with inability to do work or usual activities; signs and symptoms may be of systemic nature or require medical evaluation or treatment.
Time frame: 12 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| RFA Treatment | Tolerability | bleeding associated with bowel movements | 20 participants |
| RFA Treatment | Tolerability | anal bleeding without a bowel movement, mild | 12 participants |
| RFA Treatment | Tolerability | anal bleeding without a bowel movement, moderate | 7 participants |
| RFA Treatment | Tolerability | severe bleeding associated with a bowel movement | 1 participants |