Infrared Coagulator Ablation or Observation in Preventing Anal Cancer in HIV-Positive Patients With Anal Neoplasia

Study Overview
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Brief Summary
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RATIONALE: Infrared coagulator ablation may be effective in preventing the development of anal cancer in patients with anal neoplasia PURPOSE: This randomized phase III trial is studying infrared coagulator ablation to see how well it works compared to observation in preventing anal cancer in HIV-positive patients with anal neoplasia.

Detailed Description
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OBJECTIVES: Primary Evaluate the complete response rate at 3 months and 1 year in HIV-seropositive patients with high-grade anal intraepithelial neoplasia (HGAIN) treated with infrared coagulator (IRC) ablation versus observation. Secondary Determine the tolerability and safety of IRC ablation versus observation in these patients. Compare the proportion of patients with HGAIN at 1 year. Evaluate the response and recurrence rates at 1 year of individual lesions in patients treated with this regimen vs observation. Determine the incidence of metachronous lesions in these patients. Compare the response and recurrence rates at 2 years of individual lesions in patients under observation who subsequently received IRC ablation with the response and recurrence rates at 1 year in patients initially treated with IRC. OUTLINE: This is a multicenter study. Patients are stratified according to site. Patients are randomized to 1 of 2 arms. Arm I: Infrared coagulator (IRC) contact tip is placed in direct contact with lesion under high-resolution anoscopy (HRA) guidance for 1.5 seconds. IRC ablation is reapplied until the level of submucosal vessels are reached. One week after each IRC ablation, patients complete a questionnaire regarding pain, bleeding, and other complaints. Arm II: Patients receive standard of care and undergo observation. After 12 months, patients may receive IRC ablation to all anal intraepithelial neoplasia lesions. NOTE: Patients may receive a maximum of 6 IRC treatments while on study (3 per year). Patients undergo a physical exam, digital rectal exam, anal cytology, and HRA at baseline and periodically during study. After completion of study therapy, patients are followed up periodically for 2 years.

Official Title
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A Randomized Clinical Trial of Infrared Coagulator (IRC) Ablation Versus Expectant Management of Intra-Anal High Grade Intraepithelial Neoplasia (HGAIN) in HIV-infected Adults

Conditions
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Anal Cancer, Neoplasm of Uncertain Malignant Potential, Nonneoplastic Condition, Precancerous Condition

Intervention / Treatment
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* Other: clinical observation
* Device: infrared photocoagulation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of high-grade anal intraepithelial neoplasia (AIN) meeting the following: AIN2 and/or AIN3 confirmed by biopsy ≥ 2 weeks to ≤ 60 days before enrollment 1-3 lesions with each lesion ≤ 15 mm in diameter At least one high-grade AIN lesion is still visible at study entry HIV-infection documented by federally approved, licensed HIV-test in conjunction with screening test (e.g., ELISA, western blot, or other test) HIV-infection, based on prior ELISA and western blot assays, recorded and documented by another physician, allowed provided patient undergoes an approved antibody test to confirm diagnosis Patients on concurrent anti-retroviral therapy with a history of HIV-positivity based on an approved antibody test allowed Detectable plasma HIV-1 RNA also allowed No perianal AIN, perianal condyloma, or lower vulvar intraepithelial neoplasia or condyloma requiring treatment PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Life expectancy ≥ 2 years CD4 count ≥ 200/mm³ ANC > 750/mm³ Platelet count ≥ 75,000/mm³ Hemoglobin ≥ 9.0 g/dL INR and aPTT normal Negative pregnancy test Fertile patients must use effective contraception Female patients must have undergone cervical pap smear (if having a cervix) and gynecologic evaluation within the past 12 months Must be capable of complying with the requirements of this protocol Concurrent HPV-related disease allowed No history of anal cancer No acute infection or other serious medical illness requiring treatment within the past 14 days Fungal infection of the skin or a sexually transmitted disease requiring treatment allowed No concurrent malignancy requiring systemic therapy Kaposi sarcoma limited to the skin allowed PRIOR CONCURRENT THERAPY: No prior infrared coagulator (IRC) ablation for high-grade anal intraepithelial neoplasia (HGAIN) Prior HGAIN treated by any means other than IRC within the past 2 months allowed At least 5 days since prior coumadin or clopidogrel and ≥ 7 days after study therapy before receiving coumadin or clopidogrel again No concurrent anticoagulant therapy other than aspirin or NSAIDs More than 3 months since prior and concurrent systemic corticosteroids, cytokines, or immunomodulatory therapy (e.g., interferons) or local imiquimod No concurrent systemic therapy

Ages Eligible for Study
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Minimum Age: 27 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I: Infrared coagulator treatment<br>Infrared photocoagulation therapy. The infrared coagulator (IRC) contact tip is placed in direct contact with lesion under high-resolution anoscopy (HRA) guidance. Patients then undergo IRC ablation for 1.5 second pulses. IRC ablation is reapplied until the level of submucosal vessels are reached. | Device: infrared photocoagulation therapy<br>* Anal infrared coagulator ablation<br>* Other names: Redfield IRC;|
| Active Comparator: Arm II: Expectant management<br>Patients receive standard of care and undergo clinical observation. After 12 months, patients may receive IRC ablation to all anal intraepithelial neoplasia lesions despite of their size. | Other: clinical observation<br>* Patients undergo observation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete Response Through 1 Year | No detection of high grade anal intraepithelial neoplasia (HGAIN) from treatment through one year. Detection of HGAIN was based on local pathology reports. | 1 year post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerability and Safety of Infrared Coagulator Ablation | Number of patients who experienced a serious adverse events | All study visits through year 2 | 
| Proportion of Patients With High-grade Anal Intraepithelial Neoplasia at 1 Year | Number of patients who had high grade anal intraepithelial neoplasia at one year. | 1 year on study | 
| Recurrence Rate at 1 Year |  | 1 year on study | 
| Incidence of Metachronous Lesions | Number of patients with one or more metachronous lesions | one year on study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anal cancer, HIV infection, human papilloma virus infection, neoplasm of uncertain malignant potential, high-grade squamous intraepithelial lesion