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.
Full Title of Study: “A Randomized Clinical Trial of Infrared Coagulator (IRC) Ablation Versus Expectant Management of Intra-Anal High Grade Intraepithelial Neoplasia (HGAIN) in HIV-infected Adults”
- Study Type: Interventional
- Study Design
- Allocation: Randomized
- Intervention Model: Parallel Assignment
- Primary Purpose: Prevention
- Masking: None (Open Label)
- Study Primary Completion Date: July 2015
- 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.
- 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.
- Other: clinical observation
- Patients undergo observation
- Device: infrared photocoagulation therapy
- Anal infrared coagulator ablation
Arms, Groups and Cohorts
- Experimental: Arm I: Infrared coagulator treatment
- 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.
- Active Comparator: Arm II: Expectant management
- 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.
Clinical Trial Outcome Measures
- Complete Response Through 1 Year
- Time Frame: 1 year post treatment
- No detection of high grade anal intraepithelial neoplasia (HGAIN) from treatment through one year. Detection of HGAIN was based on local pathology reports.
- Tolerability and Safety of Infrared Coagulator Ablation
- Time Frame: All study visits through year 2
- Number of patients who experienced a serious adverse events
- Proportion of Patients With High-grade Anal Intraepithelial Neoplasia at 1 Year
- Time Frame: 1 year on study
- Number of patients who had high grade anal intraepithelial neoplasia at one year.
- Recurrence Rate at 1 Year
- Time Frame: 1 year on study
- Incidence of Metachronous Lesions
- Time Frame: one year on study
- Number of patients with one or more metachronous lesions
Participating in This Clinical Trial
- 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
- 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
Gender Eligibility: All
Minimum Age: 27 Years
Maximum Age: N/A
Are Healthy Volunteers Accepted: No
- Lead Sponsor
- AIDS Malignancy Consortium
- National Cancer Institute (NCI)
- Provider of Information About this Clinical Study
- Overall Official(s)
- Stephen E. Goldstone, MD, Principal Investigator, Laser Surgery Care
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