Anal Cancer, Neoplasm of Uncertain Malignant Potential, Nonneoplastic Condition, Precancerous Condition
Conditions
Keywords
anal cancer, HIV infection, human papilloma virus infection, neoplasm of uncertain malignant potential, high-grade squamous intraepithelial lesion
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.
Interventions
OTHERclinical observation
Patients undergo observation
Anal infrared coagulator ablation
Sponsors
National Cancer Institute (NCI)
The Emmes Company, LLC
University of Arkansas
AIDS Malignancy Consortium
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
27 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response Through 1 Year | 1 year post treatment | No detection of high grade anal intraepithelial neoplasia (HGAIN) from treatment through one year. Detection of HGAIN was based on local pathology reports. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability and Safety of Infrared Coagulator Ablation | All study visits through year 2 | Number of patients who experienced a serious adverse events |
| Proportion of Patients With High-grade Anal Intraepithelial Neoplasia at 1 Year | 1 year on study | Number of patients who had high grade anal intraepithelial neoplasia at one year. |
| Recurrence Rate at 1 Year | 1 year on study | — |
| Incidence of Metachronous Lesions | one year on study | Number of patients with one or more metachronous lesions |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
infrared photocoagulation therapy: Anal infrared coagulator ablation | 60 |
| 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.
clinical observation: Patients undergo observation | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | enrolled on other study, concomitant med | 1 | 3 |
| Overall Study | Lost to Follow-up | 3 | 6 |
| Overall Study | met protocol criteria for non-treatment | 11 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Arm I: Infrared Coagulator Treatment | Total | Arm II: Expectant Management |
|---|---|---|---|
| Age, Continuous | 50.0 years STANDARD_DEVIATION 9 | 49.8 years STANDARD_DEVIATION 9.3 | 49.0 years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 22 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 97 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 22 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 46 Participants | 92 Participants | 46 Participants |
| Region of Enrollment United States | 60 participants | 120 participants | 60 participants |
| Sex: Female, Male Female | 2 Participants | 8 Participants | 6 Participants |
| Sex: Female, Male Male | 58 Participants | 112 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 54 / 60 | 41 / 60 |
| serious Total, serious adverse events | 8 / 60 | 6 / 60 |
Outcome results
Primary
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.
Time frame: 1 year post treatment
Population: All study participants who were randomized and attended the baseline visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Infrared Coagulator Treatment | Complete Response Through 1 Year | 38 participants |
| Arm II: Expectant Management | Complete Response Through 1 Year | 16 participants |
Secondary
Incidence of Metachronous Lesions
Number of patients with one or more metachronous lesions
Time frame: one year on study
Population: Patents with any biopsy from randomization to one year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I: Infrared Coagulator Treatment | Incidence of Metachronous Lesions | 26 Participants |
| Arm II: Expectant Management | Incidence of Metachronous Lesions | 15 Participants |
Secondary
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.
Time frame: 1 year on study
Population: Patients who had an evaluable biopsy within one year after randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm I: Infrared Coagulator Treatment | Proportion of Patients With High-grade Anal Intraepithelial Neoplasia at 1 Year | 15 Participants |
| Arm II: Expectant Management | Proportion of Patients With High-grade Anal Intraepithelial Neoplasia at 1 Year | 40 Participants |
Secondary
Recurrence Rate at 1 Year
Time frame: 1 year on study
Population: Patients who were treated with IRC, no data were collected on patients on the expectant management arm
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Infrared Coagulator Treatment | Recurrence Rate at 1 Year | 37 Percentage of lesions that recurred |
Secondary
Tolerability and Safety of Infrared Coagulator Ablation
Number of patients who experienced a serious adverse events
Time frame: All study visits through year 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I: Infrared Coagulator Treatment | Tolerability and Safety of Infrared Coagulator Ablation | 8 participants |
| Arm II: Expectant Management | Tolerability and Safety of Infrared Coagulator Ablation | 6 participants |