Treatment in Preventing Anal Cancer in Patients With HIV and Anal High-Grade Lesions
Condition: Anal Cancer; High-grade Squamous Intraepithelial Lesion; HIV Infection; Human Papilloma Virus Infection
MeSH terms: Infections; Communicable Diseases; Papillomavirus Infections; Papilloma; Anus Neoplasms; Squamous Intraepithelial Lesions of the Cervix; Carcinoma, Squamous Cell; Carcinoma in Situ
Intervention: imiquimod; fluorouracil; infrared photocoagulation therapy; thermal ablation therapy; laser therapy; clinical observation; laboratory biomarker analysis
Intervention description: Applied topically; Applied topically; Undergo infrared coagulation; Undergo hyfrecation/electrocautery therapy; Undergo laser therapy; Undergo active monitoring (High Resolution Anoscopy [HRA]) with biopsies; Correlative studies
Intervention MeSH terms: Fluorouracil; Imiquimod
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: All participants are evaluated with high resolution anoscopy and anal cytology every 6 months during study participation. Participants randomized to treatment undergo biopsy of anal HSIL at each 6-month visit, and receive topical or ablative therapies for incident anal HSIL lesions. Active monitoring participants undergo close observation, with biopsy of anal HSIL at annual visits. Participants undergo biopsy of lesions at any time cancer is suspected.
Masking: None (Open Label)
Enrollment: 4446.0
Sex: All
Minimum age: 35 Years
Healthy volunteers: No
Keywords: anal cancer; high-grade squamous intraepithelial lesion; anal HSIL; HIV; HIV/AIDS; human papillomavirus; HPV

Summary:

      The randomized phase of the trial compared topical or ablative treatment with active
      monitoring in preventing anal cancer in patients with human immunodeficiency virus (HIV) and
      high-grade squamous intraepithelial lesions (HSIL). Anal HSIL is tissue in the anal canal
      that has been damaged by infection with human papillomavirus (HPV) and is at risk for turning
      into anal cancer.

      The ANCHOR Data Safety Monitoring Board (DSMB) determined that the primary study endpoint was
      completed, based on the data and statistical analysis presented to them on 07SEP2021.

      In the post-randomization phase of this trial, all enrolled participants are offered
      treatment for HSIL and/or follow-up, at the participant's choice.
    

Eligibility criteria:

        Inclusion Criteria:

          -  HIV positive. Documentation of HIV-1 infection by means of any one of the following:
             1) Documentation of HIV diagnosis in the medical record by a licensed health care
             provider; 2) Documentation of receipt of ART by a licensed health care provider
             (receipt of at least two agents is required); 3) HIV-1 RNA detection by a licensed
             HIV-1 RNA assay demonstrating >1000 RNA copies/mL; or, 4) 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.

          -  Biopsy-proven HSIL at baseline

          -  At least one focus of HSIL must be identified that is not within a condyloma that may
             be treated after enrollment into the study

          -  For females, documentation that the participant is being followed for cervical
             cytology (if having a cervix) and/or HPV testing per current ASCCP guidelines, and
             visual examination of the vulva, vagina, and cervix to rule out cancer/suspicion for
             cancer 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

          -  Platelets: >= 75,000/mm^3

          -  Hemoglobin >= 9.0 g/dL

          -  Women of childbearing potential must have a negative urine pregnancy test within 7
             days of initiating study treatment if they have been randomized to the treatment arm;
             all women of childbearing potential must agree to use a reliable birth control method
             (oral contraceptive pills, intrauterine device, Nexplanon, DepoProvera, or permanent
             sterilization, 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;
             all participants must be willing to comply with an acceptable birth control regimen as
             determined by the Investigator

          -  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.

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Participant is willing to be randomized and able to comply with the protocol

          -  Clinician is comfortable with either following patient for up to 5 years without
             therapy or treating patient for up to 5 years

        Exclusion Criteria:

          -  Inability to provide informed consent

          -  Patients who are receiving any other immunomodulatory investigational agents
             (replacement doses of steroids for adrenal insufficiency or treatment with prednisone
             ≤5 mg/day is permitted) within the 4 weeks before randomization enrollment, other than
             investigational antiretroviral agents for HIV, or investigational or approved agents
             for Hepatitis C.

          -  History of anal cancer, penile, vulvar, vaginal or cervical cancer, or signs of these
             cancers at baseline.

          -  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 without an ANCHOR
             study site during study participation