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

Cancer Type
Anal Cancer
Unknown Primary
Trial Phase
Phase III
21 Years and older, Male and Female
Study Type
Protocol IDs
AMC-088 (primary)
Study Sponsor
AIDS Malignancy Consortium


This 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, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether imiquimod or fluorouracil is more effective than observation in treating high-grade anal squamous skin lesions.


I. Complete response defined as no anal biopsies with high-grade squamous intraepithelial lesions (HSIL) and cytology without HSIL at Week 20.
II. To assess the efficacy of intra-anal topical fluorouracil (5FU) for treatment of anal HSIL compared to observation only.

I.To describe the efficacy of intra-anal imiquimod 2.5% for treatment of anal HSIL compared to observation only.
II. To assess the safety and tolerability of intra-anal imiquimod 2.5% and topical 5FU.
III. To compare the efficacy of intra-anal imiquimod 2.5% and topical 5FU.
IV. To assess for partial response of intra-anal imiquimod 2.5% or topical 5FU as compared to observation only.
V. To evaluate the effect of intra-anal imiquimod 2.5% and topical 5FU on human papilloma virus (HPV) persistence.
VI. To evaluate anal HSIL outcomes at Week 44.
VII. 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. Perianal disease is also treated if present.

ARM B: Patients apply fluorouracil intra-anally twice daily (BID) on days 1-5. Treatment repeats every 2 Weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. Perianal disease is also treated if present.

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.

Patients undergo blood sample collection during screening and biopsy throughout the study.

After completion of study treatment, patients are followed up at Weeks 20, 24, 26, 32, 40, and 44.


  1. HIV-positive, male or female, >= 21 years of age. 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) (at least two different medications, except pre-exposure prophylaxis [PrEP] regimens [e.g., Truvada]) 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) * 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 (U.S.) Federal Drug Administration (FDA)-approved assay, which is required for all investigational new drug (IND) studies
  2. Biopsy-proven HSIL (anal intraepithelial neoplasia 2 [AIN2] with a positive p16 stain, AIN 2-3, or AIN3) of the anal canal at either the squamocolumnar junction or distal anus, documented within 60 days prior to enrollment, but not less than seven days prior to randomization
  3. HSIL comprising two or more lesions, or anal HSIL in at least two octants, or anal HSIL that has recurred or is persistent after prior ablative treatment Note: HSIL should be in the anal canal at either the squamocolumnar junction or distal anus on HRA at screening or randomization; the extent of HSIL should be based on available biopsy results and visual appearance
  4. Anal HSIL lesions are visible at randomization and no lesions are suspicious for invasive cancer
  5. Ability to understand and willing to provide informed consent
  6. Participants must, in the opinion of the investigator, be capable of complying with the requirements of this protocol including self-administration of study treatment
  7. Karnofsky performance status (KPS) of >= 70% or Eastern Cooperative Oncology Group (ECOG) performance status =< 1
  8. Cluster of differentiation (CD)4 count >= 200 within 120 days prior to enrollment or plasma HIV-1 RNA < 200 copies/mL within 120 days prior to randomization
  9. 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 randomization 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 randomization
  10. Absolute neutrophil count (ANC) > 750 cells/mm^3 within 90 days prior to randomization
  11. Hemoglobin >= 9.0 g/dL within 90 days prior to randomization
  12. Platelet count >= 75,000/mm^3 within 90 days prior to randomization

Treatment Sites in Georgia

Georgia Cancer Center for Excellence at Grady

80 Jesse Hill Jr. Drive, SE
Atlanta, GA 30303

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