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

• Status: Active, not recruiting
• Trial end date: 2027-06-30
• Target enrollment: 0
• Participant gender: All

Summary

This randomized phase III trial compares 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. It is not yet known if treating HSIL is more effective than active monitoring in preventing patients from developing anal cancer.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: AIDS Malignancy Consortium
• Collaborators: National Cancer Institute (NCI); The Emmes Company, LLC; The EMMES Corporation; University of Arkansas; University of California, San Francisco
• Treatments: Fluorouracil; Imiquimod

Criteria

Inclusion Criteria:

• HIV-1 infection, as documented by any federally approved, licensed HIV test performed in conjunction with screening (or enzyme-linked immunosorbent assay [ELISA], test kit, and confirmed by western blot or other approved test); alternatively, this documentation may include a record that another physician has documented that the participant has HIV infection based on prior ELISA and western blot, or other approved diagnostic tests; an approved antibody test will be used to confirm diagnosis; if the physician is treating a patient with combination antiretroviral therapy (cART) with a history of HIV positivity based on an approved antibody test then repeat antibody confirmation is not necessary

• No history of treatment or removal of HSIL

• No history of anal cancer or signs of anal cancer at baseline, and no history of penile, vulvar, vaginal or cervical cancer

• 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, cervical cytology (if having a cervix) and gynecologic evaluation including vulvar examination 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), 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 in this study; men who could father a child should use at least two forms of birth control for 3 months after stopping all study 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 within the 4 weeks before randomization enrollment, other than investigational antiretroviral agents for HIV

• History of anal cancer, penile, vulvar, vaginal or cervical cancer

• History of prior treatment or removal of anal HSIL

• 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

• History of HPV vaccination, or intention to receive an HPV vaccine during study participation

• Prior pelvic radiation therapy that would preclude radiation therapy if anal cancer develops

• 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 during study participation