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

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.

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