NCT02059499

Imiquimod, Fluorouracil, or Observation in Treating HIV-Positive Patients With High-Grade Anal Squamous Skin Lesions

A Randomized, Phase III Study of Intra-anal Imiquimod 2.5% vs. Topical 5-fluorouracil 5% vs. Observation for the Treatment of High-grade Anal Squamous Intraepithelial Lesions in HIV-infected Men and Women

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 91 (actual)
• Sponsor: AIDS Malignancy Consortium · Network
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

This randomized phase III trial studies imiquimod or fluorouracil to see how well they work compared to observation in treating patients with high-grade anal squamous skin lesions who are human immunodeficiency virus (HIV)-positive. Biological therapies, such as imiquimod, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether imiquimod or fluorouracil is more effective than observation in treating high-grade anal squamous skin lesions.

Detailed description

PRIMARY OBJECTIVES: I. To assess the efficacy of intra-anal imiquimod 2.5% for treatment of anal high-grade squamous intraepithelial lesions (HSIL) compared to observation only. II. To assess the efficacy of intra-anal topical 5-fluorouracil (fluorouracil) 5% for treatment of anal HSIL compared to observation only. SECONDARY OBJECTIVES: I. To assess the safety and tolerability of intra-anal imiquimod 2.5% and topical 5-fluorouracil 5%. II. To compare the efficacy of intra-anal imiquimod 2.5% and topical 5-fluorouracil 5%. III. To assess for partial response of intra-anal imiquimod 2.5% or topical 5-fluorouracil 5% as compared to observation only. IV. To evaluate the effect of intra-anal imiquimod 2.5% and topical 5-fluorouracil 5% on human papilloma virus (HPV) persistence. V. To evaluate anal HSIL outcomes at week 44. VI. To evaluate the effect of behavioral patterns including tobacco smoking and sexual activity on treatment efficacy, tolerability and HPV. OUTLINE: Patients are randomized to 1 of 3 treatment arms. ARM A: Patients apply imiquimod intra-anally once daily (QD) for 16 weeks. (closed as of protocol version 5.0) ARM B: Patients apply fluorouracil intra-anally twice daily (BID) on days 1-5. Treatment repeats every 2 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. ARM C: Patients receive no treatment. Patients who still have HSIL at week 20 and who agree to randomization may cross-over to Arm A or B. After completion of study treatment, patients are followed up at weeks 20, 24, 26, 32, 40, and 44.

Conditions

• Anal Intraepithelial Neoplasia
• High-grade Squamous Intraepithelial Lesion
• HIV Infection

Interventions

Type	Name	Description
DRUG	imiquimod	Given intra-anally
DRUG	fluorouracil	Given intra-anally
OTHER	questionnaire administration	Ancillary studies
OTHER	laboratory biomarker analysis	Correlative studies

Timeline

• Start date: 2015-12-28
• Primary completion: 2023-12-05
• Completion: 2024-05-02
• First posted: 2014-02-11
• Last updated: 2025-07-23
• Results posted: 2025-05-20

Locations

13 sites across 2 countries: United States, Puerto Rico