A Randomized Clinical Trial of Infrared Coagulator (IRC) Ablation Versus Expectant Management of Intra-Anal High Grade Intraepithelial Neoplasia (HGAIN) in HIV-infected Adults
| Registry | NCT01164722 |
|---|---|
| Status | Completed |
| Phase | Phase 3 |
| Study type | Interventional; randomized, parallel, masking: none, prevention |
| Enrollment | 120 (Actual) |
| Sponsor | AIDS Malignancy Consortium (Network); collaborators: National Cancer Institute (NCI), The Emmes Company, LLC, University of Arkansas |
| Conditions | Anal Cancer, Neoplasm of Uncertain Malignant Potential, Nonneoplastic Condition, Precancerous Condition |
| Interventions | clinical observation, infrared photocoagulation therapy (Other, device) |
| Dates | start 2011-04-01, primary completion 2015-07-01, completion 2016-07-01, first posted 2010-07-19, last updated 2020-08-04 |
| Locations | 7 sites in United States |
Related Papers Related Patents Related Grants Related Experts
All trials for Anal Cancer All trials for Neoplasm of Uncertain Malignant Potential All trials of clinical observation All trials of infrared photocoagulation therapy
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Arm I: Infrared coagulator treatment | Experimental | Device: infrared photocoagulation therapy | 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. |
| Arm II: Expectant management | Active comparator | Other: clinical observation | 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. |
Sex: All, ages: 27 Years to any
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
| Milestone | Arm I: Infrared Coagulator Treatment | Arm II: Expectant Management |
|---|---|---|
| Started | 60 | 60 |
| Completed | 42 | 45 |
| Not completed | 18 | 15 |
Time frame: Study duration - maximum is 24 months
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|---|---|---|
| Arm I: Infrared Coagulator Treatment | 0 | 8/60 (13.3%) | 54/60 (90.0%) |
| Arm II: Expectant Management | 0 | 6/60 (10.0%) | 41/60 (68.3%) |
| Term | Organ system | Arm I: Infrared Coagulator Treatment | Arm II: Expectant Management |
|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | 1/60 | 0/60 |
| Acute coronary syndrome | Cardiac disorders | 1/60 | 0/60 |
| Aortic Valve Disease | Cardiac disorders | 0/60 | 1/60 |
| Cardiac Disorders, other | Cardiac disorders | 1/60 | 0/60 |
| Myocardial infarction | Cardiac disorders | 2/60 | 0/60 |
| Retinal vacular disorder | Eye disorders | 0/60 | 1/60 |
| Pancreatitis | Gastrointestinal disorders | 0/60 | 1/60 |
| Infections, other | Infections and infestations | 1/60 | 0/60 |
| Fracture | Injury, poisoning and procedural complications | 0/60 | 1/60 |
| Hip fracture | Injury, poisoning and procedural complications | 0/60 | 1/60 |
| Intraoperative musculoskeletal injury | Injury, poisoning and procedural complications | 0/60 | 1/60 |
| Neoplasms, unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/60 | 1/60 |
| Anxiety | Psychiatric disorders | 0/60 | 1/60 |
| Renal calculi | Renal and urinary disorders | 1/60 | 0/60 |
| Thromboembolic event | Vascular disorders | 1/60 | 1/60 |
| Term | Organ system | Arm I: Infrared Coagulator Treatment | Arm II: Expectant Management |
|---|---|---|---|
| Anal hemorrhage | Gastrointestinal disorders | 4/60 | 6/60 |
| Anal pain | Gastrointestinal disorders | 49/60 | 30/60 |
| Anal ulcer | Gastrointestinal disorders | 14/60 | 4/60 |
| Diarrhea | Gastrointestinal disorders | 6/60 | 4/60 |
| Hemorrhoids | Gastrointestinal disorders | 5/60 | 1/60 |
| Flu-like symptoms | General disorders | 3/60 | 4/60 |
| Anorectal infection | Infections and infestations | 3/60 | 4/60 |
| Infections,other | Infections and infestations | 2/60 | 5/60 |
| Skin infection | Infections and infestations | 2/60 | 4/60 |
| Postoperative hemorrhage | Injury, poisoning and procedural complications | 45/60 | 20/60 |
| back pain | Musculoskeletal and connective tissue disorders | 3/60 | 4/60 |
| Musculoskeletal disorder, other | Musculoskeletal and connective tissue disorders | 5/60 | 4/60 |
| Neck pain | Musculoskeletal and connective tissue disorders | 0/60 | 4/60 |
| Pruritus | Skin and subcutaneous tissue disorders | 4/60 | 0/60 |
| Skin and subcutaneous tissue disorder, other | Skin and subcutaneous tissue disorders | 2/60 | 6/60 |
| Facility | City | Country | Status |
|---|---|---|---|
| UCLA Clinical AIDS Research and Education (CARE) Center | Los Angeles, California | United States | |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California | United States | |
| Boston University Cancer Research Center | Boston, Massachusetts | United States | |
| Laser Surgery Care | New York, New York | United States | |
| New York Weill Cornell Cancer Center at Cornell University | New York, New York | United States | |
| University of Pittsburgh Medical Center | Pittsburgh, Pennsylvania | United States | |
| Benaroya Research Institute at Virginia Mason Medical Center | Seattle, Washington | United States |
NIH grants: U01CA121947