Clinical trial NCT01164722: Infrared Coagulator Ablation or Observation in Preventing Anal Cancer in HIV-Positive Patients With Anal Neoplasia
Official title: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: Anal Cancer
Neoplasm of Uncertain Malignant Potential
Nonneoplastic Condition
Precancerous Condition
Keywords: anal cancer
HIV infection
human papilloma virus infection
neoplasm of uncertain malignant potential
high-grade squamous intraepithelial lesion
Lead sponsor: AIDS Malignancy Consortium
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
name: The Emmes Company, LLC
name: University of Arkansas
First posted: 2010-07-19
Enrollment: 120
Sex: ALL
Minimum age (years): 27
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: 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

Primary outcomes:
measure: Complete Response Through 1 Year
timeFrame: 1 year post treatment
Secondary outcomes:
measure: Tolerability and Safety of Infrared Coagulator Ablation
timeFrame: All study visits through year 2
measure: Proportion of Patients With High-grade Anal Intraepithelial Neoplasia at 1 Year
timeFrame: 1 year on study
measure: Recurrence Rate at 1 Year
timeFrame: 1 year on study
measure: Incidence of Metachronous Lesions
timeFrame: one year on study
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Clinical AIDS Research and Education (CARE) Center
state: California
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: New York
country: United States
facility: Laser Surgery Care
state: New York
city: New York
country: United States
facility: New York Weill Cornell Cancer Center at Cornell University
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason Medical Center
state: Washington
Study officials:
affiliation: Laser Surgery Care
name: Stephen E. Goldstone, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goldstone SE, Lensing SY, Stier EA, Darragh T, Lee JY, van Zante A, Jay N, Berry-Lawhorn JM, Cranston RD, Mitsuyasu R, Aboulafia D, Palefsky JM, Wilkin T. A Randomized Clinical Trial of Infrared Coagulation Ablation Versus Active Monitoring of Intra-anal High-grade Dysplasia in Adults With Human Immunodeficiency Virus Infection: An AIDS Malignancy Consortium Trial. Clin Infect Dis. 2019 Mar 19;68(7):1204-1212. doi: 10.1093/cid/ciy615.