infrared coagulator ablation or observation in preventing anal cancer in hiv-positive patients with anal neoplasia

Conditions: Anal Cancer; Neoplasm of Uncertain Malignant Potential; Nonneoplastic Condition; Precancerous Condition

Summary: 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.

Eligibility criteria:
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

Keywords: anal cancer hiv infection human papilloma virus infection neoplasm of uncertain malignant potential high-grade squamous intraepithelial lesion