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

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

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.

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