Topical or Ablative Treatment in Preventing Anal Cancer in Patients with HIV and Anal High-Grade Squamous Intraepithelial Lesions
- 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
- 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)
- 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 for the ANCHOR Study and SARS-CoV-2 ancillary study, and is being enrolled at one of the participating centers for this study
- 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
District of Columbia
I. To determine whether treating anal HSIL is effective in reducing the incidence of anal cancer in HIV-infected men and women.
I. To determine the safety of infrared coagulation, electrocautery, imiquimod, laser, and 5-fluorouracil (fluorouracil) treatments for anal HSIL.
II. To assess the responsiveness (sensitivity to change) and clinical significance of the Anal Cancer/HSIL Outcomes Research (ANCHOR) Study Health-Related Symptom Index (A-HRSI) subscales by comparing change scores within groups of participants as defined by participant responses to the Patient Global Impression of Change (PGIC) item.
I. Determine the HPV type in cancer and compare to that of overlying HSIL and HSIL biopsies collected concurrently that did not progress to cancer.
II. Determine the strain variant of HPV 16 in participants who progressed to anal cancer and compare to participants with HSIL biopsies who did not progress to cancer.
III. Determine the HPV integration site in overlying anal cancer to that of HSIL overlying the cancer and HSIL biopsies collected concurrently that did not progress to cancer.
IV. Perform gene expression array analysis comparing expression in anal cancer with HSIL overlying the cancer; perform gene expression array analysis comparing expression in HSIL biopsies that progressed to cancer with non-progressing HSIL biopsies at other locations; perform similar analyses comparing expression in HSIL biopsies that progressed to cancer with the same lesion at earlier time points prior to progression.
V. Characterize genetic changes in anal cancers compared with HSIL overlying the cancer; characterize genetic changes in HSIL biopsies that progressed to cancer compared with non-progressing HSIL biopsies at other locations; characterize genetic changes HSIL biopsies that progressed to cancer with the same lesion at earlier time points prior to progression.
VI. Identify host and viral biomarkers of progression from HSIL to cancer.
VII. Evaluate medical history and behavioral risk factors for HSIL progression to cancer.
QUALITY OF LIFE OBJECTIVES:
I. To compare arms in terms of changes in physical symptoms and impacts from T2 to T3, adjusting for T1. (Primary quality of life [QOL] Objective)
II. To compare arms in terms of changes in psychological symptoms from T3 to T4, adjusting for T1. (Secondary QOL Objective)
III. To assess of long-term health related (HR)-QoL changes in physical symptoms/impacts and psychological symptoms from T4 through the subsequent T5-T8 follow-ups overall and by arm. (Exploratory QOL Objective)
ANCILLARY STUDY OBJECTIVES:
I. Determine the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection in anal and oropharyngeal swabs among people living with HIV (PLWH) being screened for the ANCHOR study.
II. Determine the relationship in the ANCHOR screening population between prevalent anal SARS-CoV-2 positivity, anal HPV infection, and anal high-grade squamous intraepithelial lesions (HSIL).
III. Determine the 6-month incidence of SARS-CoV-2 detection in anal and oropharyngeal swabs among participants with anal HSIL newly enrolled into the ANCHOR study.
IV. Determine the relationship between prevalent or incident SARS-CoV-2 detection and regression of anal HPV infection or HSIL among participants newly enrolled into the ANCHOR study and who are randomized to the monitoring arm.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I: Patients are directed to receive either topical or ablative treatment at the discretion of the clinician. Patients receiving topical treatment apply imiquimod intra-anally, peri-anally, or both thrice weekly for up to 16 weeks or fluorouracil twice daily for 5 days every 2 weeks for up to 16 weeks. Patients receiving ablative treatment undergo infrared coagulation, hyfrecation/electrocautery, or laser. Patients may undergo excision under anesthesia if the clinician believes none of the other treatment approaches will be effective. The number and timing of such treatments will be at the discretion of the investigator. Patients with persistent HSIL should continue a protocol-approved treatment or a new protocol treatment should be considered.
ARM II: Patients undergo active monitoring with high resolution anal examinations and biopsies of visible lesions every 6 months. Patients have cytology performed at every visit. At the final study visit, patients undergo biopsy of all visible lesions or a random 4-quadrant biopsy if no lesions are seen.
All participants will be followed up to every 6 months for 5 years after the last participant’s date of randomization, diagnosis of invasive anal cancer, or until death, whichever occurs first.
Trial Phase Phase III
Trial Type Prevention
AIDS Malignancy Consortium
- Primary ID AMC-A01
- Secondary IDs NCI-2014-00636
- Clinicaltrials.gov ID NCT02135419