Topical or Ablative Treatment in Preventing Anal Cancer in Patients with HIV and Anal High-Grade Squamous Intraepithelial Lesions

Inclusion Criteria

• HIV positive; documentation of HIV-1 infection by means of any one of the following: * Documentation of HIV diagnosis in the medical record by a licensed health care provider; * Documentation of receipt of antiretroviral therapy (ART) by a licensed health care provider (documentation may be a record of an ART prescription in the participant’s medical record, a written prescription in the name of the participant for ART, or pill bottles for ART with a label showing the participant’s name; receipt of at least two agents is required; each component agent of a multi-class combination ART regimen will be counted toward the 2-agent requirement, excepting receipt of a pre-exposure prophylaxis [PrEP] regimen alone [e.g., Truvada], which is exclusionary); * HIV-1 ribonucleic acid (RNA) detection by a licensed HIV-1 RNA assay demonstrating > 1000 RNA copies/mL; * Any licensed HIV screening antibody and/or HIV antibody/antigen combination assay confirmed by a second licensed HIV assay such as a HIV-1 western blot confirmation or HIV rapid multispot antibody differentiation assay * NOTE: A “licensed” assay refers to a United States (US) Food and Drug Administration (FDA)-approved assay, which is required for all investigational new drug (IND) studies
• Age 35 years or older. This age restriction is intended to enrich the study population at risk for cancer since anal cancer occurs only rarely under this age even among HIV-infected individuals. Fewer than 1% of anal cancers occur under the age of 35 years.
• Biopsy-proven anal HSIL at baseline (anal intraepithelial neoplasia [AIN]2 with a positive cyclin-dependent kinase inhibitor 2A [p16] stain, AIN2-3, or AIN3)
• At least one focus of HSIL must be identified that is not within a condyloma that may be treated after enrollment into the study; this requirement is to ensure that there will still be at least one focus of HSIL among participants in the Active Monitoring Arm even if they undergo treatment for condyloma
• For females, documentation that the participant is being followed with cervical cytology and/or HPV testing per current “Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents” and American Society for Colposcopy and Cervical Pathology (ASCCP) guidelines; cervical cytology must be performed prior to enrollment for women who are overdue for screening per the guidelines; women should also have confirmation of absence of cancer or suspected cancer upon visual examination of the vulva, vagina, and cervix within 12 months prior to enrollment
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Life expectancy of greater than 5 years
• Absolute neutrophil count: >= 750/mm^3 (within 90 days before enrollment)
• Platelets: >= 75,000/mm^3 (within 90 days before enrollment)
• Hemoglobin >= 9.0 g/dL (within 90 days before enrollment)
• Women of childbearing potential (FCBP) must have a negative urine pregnancy test within 7 days prior to randomization enrollment; female participants enrolled in the treatment arm are advised to not become pregnant during study participation due to the risks of the study treatments; all women of childbearing potential must agree to either commit to continued abstinence from heterosexual intercourse or to use a reliable birth control method during heterosexual intercourse (oral contraceptive pills, intrauterine device, Nexplanon, DepoProvera, or bilateral tubal ligation, etc., or another acceptable method as determined by the investigator) during the entire period of the trial (5 years or more), and must not intend to become pregnant during study participation and for 3 months after treatment is discontinued if the participant is enrolled in the treatment arm; female participants, if engaging in heterosexual intercourse, must be willing to comply with an acceptable birth control regimen as determined by the investigator * A female of childbearing potential is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months); 3) has not undergone bilateral tubal ligation
• Men randomized to the treatment arm should not father a baby while receiving topical treatment during this study; men who could father a child must agree to use at least one form of birth control during or continued abstinence from heterosexual intercourse if receiving topical treatment during the study, and for 2 weeks after stopping topical treatment
• Participant is willing to be randomized and able to comply with the protocol
• Clinician is comfortable that cancer has adequately been ruled out and is willing to follow the participant for up to 5 years without treatment of the HSIL
• HEALTH RELATED QUALITY OF LIFE (HRQoL) SUBSTUDY
• Participant has consented for the ANCHOR Study and the A-HRSI scale responsiveness substudy
• Fluent in English
• The participant is willing to conduct a phone interview with Memorial Sloan Kettering (MSK) if questionnaires are not completed at the site or as self-administered
• Participant is in screening for ANCHOR and the investigator can report a target randomization date for the participant
• QOL OBJECTIVE: Participant has consented for the ANCHOR Study and A-HRSI questionnaire completion
• QOL OBJECTIVE: Fluent in English or Spanish
• QOL OBJECTIVE: The participant is willing to conduct a phone interview with site staff if questionnaires are not completed at the site or as self-administered
• QOL OBJECTIVE: Participant is in screening for ANCHOR and the investigator plans to randomize the participant based on screening anal biopsy results
• SARS-CoV-2 ANCILLARY STUDY: Participant has consented or reconsented for the ANCHOR Study and SARS-CoV-2 ancillary study, and is being enrolled at one of the participating centers for this study

Exclusion Criteria

• Participant is unable to provide informed consent
• Participants who received any other chronic (defined as more than 50% of the time in the last 6 months) systemic immunomodulatory agents (replacement doses of steroids for adrenal insufficiency are permitted or treatment with prednisone =< 5 mg/day); receipt of investigational agents within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV and investigational or approved agents for hepatitis C, are also exclusionary
• History of anal cancer, penile, vulvar, vaginal, or cervical cancer, or signs of any of these malignancies at baseline; participants with prior carcinoma in situ will not be considered to have prior cancer for eligibility purposes
• Treatment or removal of HSIL less than 6 months prior to randomization
• Participant has symptoms related to HSIL and would benefit more from immediate treatment than from entry into the study and potential for randomization to active monitoring arm
• Current systemic chemotherapy or radiation therapy that potentially causes bone marrow suppression that would preclude safe treatment of HSIL
• Participants who only have a single HSIL lesion that is likely to be removed entirely with the initial screening biopsy
• Warts so extensive that they preclude the clinician from determining the extent and location of HSIL
• Participant plans to relocate away from the study site to a location that does not have an ANCHOR study site during study participation