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.

Study Overview

• Status: Completed
• Conditions: Precancerous Condition; Anal Cancer; Nonneoplastic Condition; Neoplasm of Uncertain Malignant Potential
• Intervention / Treatment: Other: clinical observation; Device: infrared photocoagulation therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1793
      • UCLA Clinical AIDS Research and Education (CARE) Center
    • San Francisco, California, United States, 94143
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
  • New York
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • New York, New York, United States, 10010
      • Laser Surgery Care
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute at Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 27 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Device: infrared photocoagulation therapy; Anal infrared coagulator ablation; Other Names: Redfield Infrared Coagulator; Redfield IRC
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.	Other: clinical observation; Patients undergo observation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Through 1 Year	No detection of high grade anal intraepithelial neoplasia (HGAIN) from treatment through one year. Detection of HGAIN was based on local pathology reports.	1 year post treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability and Safety of Infrared Coagulator Ablation	Number of patients who experienced a serious adverse events	All study visits through year 2
Proportion of Patients With High-grade Anal Intraepithelial Neoplasia at 1 Year	Number of patients who had high grade anal intraepithelial neoplasia at one year.	1 year on study
Recurrence Rate at 1 Year		1 year on study
Incidence of Metachronous Lesions	Number of patients with one or more metachronous lesions	one year on study

Collaborators and Investigators

• Sponsor: AIDS Malignancy Consortium
• Collaborators: National Cancer Institute (NCI); University of Arkansas; The Emmes Company, LLC
• Investigators: Principal Investigator: Stephen E. Goldstone, MD, Laser Surgery Care

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (ACTUAL): July 1, 2015
• Study Completion (ACTUAL): July 1, 2016

Study Registration Dates

• First Submitted: July 16, 2010
• First Submitted That Met QC Criteria: July 16, 2010
• First Posted (ESTIMATE): July 19, 2010

Study Record Updates

• Last Update Posted (ACTUAL): August 4, 2020
• Last Update Submitted That Met QC Criteria: July 28, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: HIV infection; human papilloma virus infection; anal cancer; high-grade squamous intraepithelial lesion; neoplasm of uncertain malignant potential
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Disease; Precancerous Conditions; Anus Neoplasms
• Other Study ID Numbers: AMC-076 (OTHER: AMC); U01CA121947 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO